Category: 7. Science

The US Space Force’s (USSF) Boeing-built X-37B Orbital Test Vehicle (OTV) lifted off on its eighth mission aboard a SpaceX Falcon 9 rocket from Kennedy Space Center in Florida.

The vehicle is “healthy” on orbit and “proceeding with standard checkout”, Boeing said.

Enhancements to the X-37B include a Boeing-developed integrated service module designed to augment the vehicle’s payload capacity, enabling more extensive experimentation while in orbit.

Boeing Space and Mission Systems vice president Michelle Parker said: “Our role is to make sure the spaceplane is the most reliable testbed it can be. None of this happens without teamwork. Launch is the starting line for this mission, but the work that follows – the quiet, methodical work on orbit, analysis and eventual return is where progress is earned.”

On its current mission, the X-37B is carrying out multiple technology demonstrations in collaboration with government agencies.

These include experiments with laser communications and a quantum inertial sensor aimed at providing navigation solutions when GPS is not accessible.

Space Launch Delta 45 commander colonel Brian Chatman said: “X-37B continues to prove itself as a premier testing platform aiding in experiments to better understand our future in space.

“These experiments, X-37B itself, and Space Launch Delta 45’s ability to perform fast, flexible launches all play crucial roles in bolstering our resilience and enhancing our ability to swiftly adapt to the challenges in space of today and tomorrow.”

This latest mission comes on the heels of the X-37B’s seventh mission, where the vehicle performed an aerobraking manoeuvre to alter its orbit while conserving fuel.

Launched in October last year, the mission concluded with a landing at Vandenberg Space Force Base in California on 7 March 2025.

The X-37B project is a collaborative effort between government and industry, spearheaded by the US Air Force Rapid Capabilities Office and managed operationally by the USSF.

Teams from Boeing located in Seal Beach, California, and Kennedy Space Center are responsible for designing, constructing, integrating, and operating this versatile spaceplane.

Since its inaugural flight in 2010, the X-37B has spent over 4,200 days in orbit.

Each mission concludes with a return to Earth for thorough inspection and necessary upgrades.

Chatman added: “The data we gather from the X-37B speeds decisions, hardens our architectures, and helps Guardians stay connected and on course even in contested environments. This is how we move from promising ideas to fieldable capability at pace.”

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UNIVERSITY PARK, Pa. — Plants have a sophisticated internal communication system to help them optimize energy production. Now, a new study by an international team of scientists led by Penn State researchers reveals for the first time the molecular messengers that control how and when plants “breathe” and “eat,” which could have implications for agriculture.

“This discovery significantly advances our understanding of how plants coordinate their internal metabolism — the chemical reactions they use to make energy — with their external environment, a fundamental process for plant growth and survival,” said Sarah Assmann, Waller Professor of Plant Biology at Penn State and corresponding author on the study published today (Aug. 25) in the journal Nature Plants. “Our findings open doors for future research into improving plant resilience and crop yields.”

For decades, plant scientists have tried to understand how the internal cells of a leaf communicate with guard cells, specialized cells in the outermost cell layer of the leaf. Pairs of guard cells encircle and control the width of stomata, the microscopic pores in the outer layer of the leaf that impact vital processes like energy production and water loss.

Stomata serve as microscopic “mouths” on leaves, opening and closing to control the intake of carbon dioxide (CO2), essential for making the carbohydrates that provide energy to the plant. Stomata also control the release of water vapor back into the atmosphere, Assmann explained. While it was known that guard cells open stomata in response to light, which drives photosynthesis, and there has long been evidence of a chemical “messenger” from inside the leaf that guides this process, the identity of the messenger had remained elusive.

“There is always a tradeoff for terrestrial plants between maximizing CO2 intake, which is needed for photosynthesis, and letting out water vapor, which can dry out the plant and ultimately kill it if it loses too much water,” Assmann said. “The stomata are the pores where that tradeoff takes place. When they open, they let in CO2 that allows the plant to feed, but they also let out water vapor, which dehydrates the plant. We knew there had to be some kind of messenger telling the guard cells how to regulate that life-or-death decision.”

Their research, conducted on mouse-ear cress — scientific name Arabidopsis thaliana — and fava beans, or Vicia faba, revealed that sugars, along with maleic acid, a chemical involved in energy production, act as these crucial messengers.

The scientists identified and characterized the molecular feedback loop between photosynthetic activity and stomatal regulation through a long series of painstaking experiments.

First, they carefully extracted apoplastic fluid, the liquid found between plant cells, from leaves exposed to either red light, which stimulates high photosynthesis, or darkness. By isolating and characterizing chemical compounds or “metabolites” in the fluid, they hypothesized they would be able to find the messenger traveling through the fluid, much like spotting a mail carrier on a busy city intersection.

By analyzing the chemical composition of the apoplastic fluid, the researchers identified a total of 448 unique chemical compounds — many more than were previously known — that are essential for basic plant functions like growth and development.

“We identified hundreds of metabolites in apoplastic fluid, which no one had analyzed to this extent before,” Assmann said. “That, on its own, is an important contribution to the field, independent of the research question that we specifically were addressing, because it gives a lot of leads on other potential signaling molecules for processes throughout the plant.”

Through extensive analysis of this fluid, the researchers identified sugars — including sucrose, fructose and glucose — and maleic acid as significant components that increased under red light, which activates photosynthesis. The researchers hypothesized that those particular metabolites would be able to enhance stomatal opening under red light.

To test their hypothesis, the researchers peeled off the thin outer layers of the leaf and exposed them to light in the presence or absence of sugars. They observed that the sugars indeed directly promoted stomatal opening in the isolated epidermis under red light. Next, they conducted a series of experiments on full leaves, using sugar feeding coupled with measurements of CO2 uptake and water loss to confirm that sugars signaled the stomata to open more widely.

Finally, they performed tests on single cells that revealed how sugars stimulate the molecular mechanisms that underlie guard cell control of stomatal opening. Overall, the work provides the first complete picture of this internal communication process within plants that can determine their survival in a range of climates, Assmann said.

“We’re focused on understanding how plants sense and respond to environmental conditions,” she said. “Plants can’t uproot themselves and find somewhere else to live; they have to deal with whatever the environment throws at them — increasingly drought and heat stress — so we study what makes plants resilient, from the very specific molecular level all the way up to whole plant physiology and field experiments, with the goal of improving crop productivity.”

Other Penn State authors are doctoral student Yunqing Zhou and Associate Professor of Biology Timothy Jegla, and postdoctoral scholars Mengmeng Zhu and Yotam Zait, who is now an assistant professor at The Hebrew University of Jerusalem and led the research. Other authors are Adi Yaaran and Sunheng Yon of The Hebrew University of Jerusalem; Eigo Ando, Yuki Hayashi and Toshinori Kinoshita of Nagoya University in Japan; Mami Okamoto and Masami Y. Hirai of the RIKEN Center for Sustainable Resource Science; and Sixue Chen of the University of Mississippi.

The U.S. National Science Foundation funded the Penn State aspects of this work.

At Penn State, researchers are solving real problems that impact the health, safety and quality of life of people across the commonwealth, the nation and around the world. 

For decades, federal support for research has fueled innovation that makes our country safer, our industries more competitive and our economy stronger. Recent federal funding cuts threaten this progress. 

Learn more about the implications of federal funding cuts to our future at Research or Regress.  

A team using MeerKAT in South Africa spotted a new repeating source of short, sharp radio pulses and, within days, tracked it through an intense outburst that produced hundreds of events across multiple frequency bands.

These bursts belong to a class known as fast radio burst (FRB) events, which last only milliseconds and come from far beyond our galaxy, with properties that let astronomers study matter scattered across the universe.

Capturing the radio bursts

Lead author Jun Tian of the Jodrell Bank Centre for Astrophysics at The University of Manchester (JBCA) and collaborators in the MeerTRAP project used MeerKAT’s real time system to search for fast transients while other observations were running.

“FRB 20240619D was first discovered on 2024 June 19 with three bursts being detected within two minutes in the MeerKAT L-band,” wrote Tian.

A week later, the team followed up across ultra high frequency, L band, and S band and recorded a total of 249 bursts.

That pace puts the source among the most active repeaters seen so far, and it gives scientists a rare chance to compare how burst counts change with observing frequency in the same time window.

What the radio bursts revealed

The catalog shows a clear frequency preference during the campaign, with far more activity centered in the L band than at lower or higher radio frequencies, a clue that the burst energy distribution turns over near that range.

Individual pulses are often confined to slices of the band rather than filling the entire tuning, and some show substructures that drift downward in frequency over time, a pattern common in repeaters and important for modeling the emission region.

In several other repeaters, microsecond and even nanosecond scale features have been measured, pointing to compact emission zones and rapid variability that are hard to reconcile with distant shock models.

The new source adds to that picture by presenting complex, sometimes multi-component bursts that change their frequency drift from one sub burst to the next, which strengthens the case for small scale structure close to the engine.

Polarization plays a role

Polarimetric data show most bursts are nearly fully linearly polarized, with a significant minority carrying measurable circular polarization, a combination that narrows the viable physical models for where and how these pulses arise.

Highly ordered polarization and fast microstructure often point to emission produced in or very near the magnetic environment of a magnetar, rather than far from the star in an external shock, as seen in other active repeaters.

Across the pulse window, the polarization angle can stay flat, swing smoothly, or jump between levels, which hints at dynamic geometry or propagation effects in the local plasma around the source.

No optical flash, tighter limits

Alongside the radio work, the team coordinated optical observations with the MeerLICHT telescope and reported a stringent upper limit on any simultaneous optical flash at the burst times 

“We find no optical counterpart of FRB 20240619D in the MeerLICHT optical observations,” wrote Tian.

For context, independent programs have been pushing optical searches to millisecond time resolution and are beginning to set even deeper fluence ratio limits in other repeating sources.

This helps to rule out bright optical companions to the radio bursts on those time scales.

Tracking the source

Astronomers have long debated whether repeating and non-repeating FRBs come from the same kind of source or if they reflect different origins.

Some models suggest highly magnetized neutron stars undergoing starquakes, while others point to interactions between compact objects in binary systems.

The extreme activity of FRB 20240619D gives researchers a chance to test these ideas against detailed data.

Earlier repeaters such as FRB 20121102A and FRB 20201124A also produced storms of hundreds of bursts per hour, and the similarities between them and the new source could mean there is a common underlying mechanism.

Careful comparison of their timing, polarization, and frequency behavior will be crucial for narrowing down which physical processes are responsible.

Why deep space radio bursts matter

By capturing hundreds of radio bursts in a very short period of time, the well documented campaign lets researchers take several important steps.

They can test how burst counts scale with radio fluence, measure dispersion measure and rotation measure precisely, and compare activity across frequencies without months of waiting.

Because FRBs accumulate signals as they cross intergalactic space, they can trace otherwise invisible ionized gas, so tracking their activity and pinpointing hosts helps map the cosmic web and its missing baryons.

The study is published in Monthly Notices of the Royal Astronomical Society.

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Structure-based RBD multimer design to enhance stability and human ACE2 binding affinity

Extensive characterization of spike protein residues 319-541, previously considered the RBD required for human ACE2 (hACE2) binding^26,27, showed that this recombinant RBD protein fragment tends to dimerize, potentially forming higher-order multimers, due to the presence of an unpaired cysteine residue (C538) close to the C-terminus^16,28. To prevent this dimerization activity in our constructs, we used a previously reported cryo-electron microscopy structure (PDB ID: 6VXX) to design a longer truncated RBD spanning residues 319-591 that allows formation of disulfide bonds between C538 and C590 (Fig. 1A)¹⁶. Subsequent molecular dynamics (MD) simulations showed that RBD (319-591) was more stable than RBD (319-541), and had a lower RMSD than that of RBD (319-541) (RMSD = 2.5 Å versus ~5 Å, RBD (319-591) versus RBD (319-541); Fig. 1B), we therefore used RBD (319-591) in the following experiments.

In order to counteract the binding of the trimeric SARS-CoV-2 spike protein to the hACE2 receptor, the recombinant RBD needs to exhibit high affinity towards hACE2. To achieve this, we engineered several RBD (319–591) constructs, including a monomer, a set of oligomers (2–3 RBD units in length), and a set of oligomers (2–4 RBD units) fused to a human IgG1 Fc domain (Fig. 1A), as attempts to incorporate additional RBD copies led to significantly reduced protein yields. We then verified their size and purity through SDS-PAGE and size-exclusion chromatography (Fig. 1C and Supplementary Fig. 1A).

Characterization of the tertiary structure of 4RBD-Fc by negative-stain electron microscopy (EM) revealed that it tends to form a beads-on-a-string-like architecture, with multiple RBD subunits loosely arranged around a central base, suggesting the dimerization of two 4RBD-Fc molecules (Fig. 1D). Each RBD subunit appeared intact and was connected via flexible glycine–serine linkers, while the central base was composed of two dimerized human IgG1 Fc domains. Due to the flexible linkers, the exact orientation of the receptor-binding motifs (residues 437–508) could not be precisely resolved; however, the arrangement appears compatible with accessibility for ACE2 binding.

To probe interactions between the RBD oligomers and hACE2, we next conducted cell-surface-binding assays using flow cytometry. Series-diluted RBD constructs were incubated with hACE2-expressing cell line (293T-hACE2) in the presence of 100 nM AlexaFluor 488-labeled RBD protein. This analysis revealed that the K_d value of RBD monomer was 36.6 ± 10.2 nM, whereas the K_d values for the oligomers were 1.7 ± 0.5 nM (2RBD), 1.4 ± 0.4 nM (3RBD), 4.8 ± 1.4 nM (RBD-Fc), 2.7 ± 0.8 nM (2RBD-Fc), 1.9 ± 0.6 nM (3RBD-Fc), and 0.8 ± 0.2 nM (4RBD-Fc) (Fig. 1E). 3RBD in the RBD oligomers and 4RBD-Fc in the Fc-fused RBD oligomers exhibit the two strongest binding capability for hACE2, being 26-fold and 46-fold higher than the RBD monomer, respectively. Therefore, they were chosen for further experiments. These results suggested that the oligomeric and Fc-fused RBD proteins retained the functionality of native RBD and could potentially interact with ACE2 more robustly.

Evaluation of 4RBD-Fc as an effective broad-spectrum blocker for SARS-CoV-2 variants in vitro

The inhibitory effects of RBD oligomers on viral entry was assessed using SARS-CoV-2 pseudovirus blocking assays. 293T-hACE2 cells, pre-incubated with RBD oligomers and then infected with a luciferase-reporter pseudovirus displaying the wild-type (WT) SARS-CoV-2 spike protein²⁹, exhibited reduced luminescence compared to non-pre-incubated cells, suggesting inhibition of spike protein-mediated entry. Dose-dependent luminescence reduction post-infection was observed with RBD monomer, 3RBD, and 4RBD-Fc (Fig. 1F), while 4RBD-Fc showed the highest inhibition (IC₅₀ = 0.27 ± 0.08 nM), outperforming both RBD monomer (IC₅₀ = 4.7 ± 1.5 nM) and 3RBD (IC₅₀ = 0.27 ± 0.08 nM). Consequently, 4RBD-Fc was selected for further study.

Acknowledging the limitation of pseudovirus studies, we further extended our investigation to clinically isolated SASR-CoV-2 viruses using Vero E6 cells in a biosafety level 3 (BSL-3) laboratory. Similar to the results of pseudovirus blocking assays, 4RBD-Fc pre-incubation effectively reduced viral load (measured by qRT-PCR) in Vero E6 cells infected with WT SARS-CoV-2 and two variants, including Delta (B.1.617.2) and BA.2 (B.1.1.529.2), with IC₅₀ of 17.3 ± 4.3 nM, 5.2 ± 4.2 nM, and 11.6 ± 5 nM, respectively (Fig. 1G). These outcomes suggest that the interaction of 4RBD-Fc with ACE2 effectively blocks the entry of various SARS-CoV-2 variants in vitro. Overall, these results demonstrate the exceptional blocking activity of 4RBD-Fc for SARS-CoV-2 among the other RBD constructs, and its potential as a broad-spectrum antiviral agent for SARS-CoV-2 variants.

Immunogenicity assessment of RBD oligomers

Next, we assessed whether these RBD oligomers retained immunogenicity by testing a single dose of intramuscular (i.m.) immunization with 10 μg of RBD, 3RBD, or 4RBD-Fc antigens in BALB/c mice, using CpG and aluminum hydroxide gel (Alum) as adjuvants. Serum samples were then collected for antibody titers and pseudovirus neutralization analysis (Fig. 1H). Enzyme-linked immunosorbent assay (ELISA) analysis of anti-RBD IgG antibodies in serum revealed that the 4RBD-Fc group exhibited the highest antibody titers (1 × 10⁴), surpassing those of the RBD (3.2 × 10³) and 3RBD groups (5 × 10³) (Fig. 1I). Additionally, pseudovirus neutralization assays demonstrated that serum from the 4RBD-Fc group had a significantly higher neutralization capacity against WT SARS-CoV-2 pseudovirus (IC₅₀ = 3934) compared to the RBD (IC₅₀ = 1086) and 3RBD groups (IC₅₀ = 796.8) (Fig. 1J). These data suggest that the RBD oligomers retained their immunogenicity, with 4RBD-Fc generating stronger binding and neutralizing antibody levels compared to RBD and 3RBD.

Restricted 4RBD-Fc distribution in the respiratory system avoids inducing inflammation or allergic reactions

To assess the suitability of 4RBD-Fc as an antiviral agent, we investigated its in vivo distribution kinetics via i.n. administration of 1 mg AlexaFluor 750-labeled 4RBD-Fc (4RBD-Fc-AF750) to K18-hACE2 mice (Fig. 2A). Given that murine ACE2 receptor does not bind to the RBD of SARS-CoV-2³⁰, we employed K18-hACE2 mice, which express hACE2 driven by the cytokeratin-18 (K18) promoter in epithelial cells³¹. Bioimaging of whole mice in vivo and in ex vivo dissected organs showed that 4RBD-Fc rapidly localized to lungs within 4 hours (Fig. 2B–E) and remained detectable in both the upper and lower respiratory tract (Fig. 2C, D) for at least 168 hours (Fig. 2B, E), indicating high stability of 4RBD-Fc in the respiratory tract microenvironment. During the initial 96 hours post-administration, the AF750 signal in the bioimaging data was confined to the respiratory tract, suggesting restricted localization of the 4RBD-Fc (Supplementary Fig. 2A–C). However, at 96 hours post-administration, 4RBD-Fc signal could be observed in ex vivo liver and kidney tissues, suggesting possible degradation or transport of 4RBD-Fc (Supplementary Fig. 2B, C). Importantly, by 336 hours (14 days) post-administration, AF750 signals had become undetectable in the respiratory tract in the majority of mice, with only one mouse showing a faint signal in the nasal cavity and lungs—demonstrating effective clearance of the protein from the respiratory system over time (Fig. 2E). Overall, these findings indicate that 4RBD-Fc exhibits strong and specific localization to the respiratory tract at early stage, prolonged local stability, and minimal systemic exposure, making it a promising candidate for intranasal antiviral therapy.

To further assess the safety of intranasally administered 4RBD-Fc, we conducted both pulmonary and systemic evaluations in K18-hACE2 mice. Mice were intranasally administered with either 1 mg of 4RBD-Fc or an equal volume of PBS (vehicle control) (Supplementary Fig. 3A). Throughout the 7-day observation period, mice were monitored daily for body weight, behavior (including activity and grooming), and general appearance (fur condition and posture), and no adverse clinical signs were observed in the 4RBD-Fc-treated group compared to the vehicle group. At 7 days post-administration, flow cytometry analysis of lung single-cell suspensions showed no significant difference in immune cell infiltration, including total leukocytes and four types of granulocytes (neutrophils, eosinophils, basophils, and mast cells), between the two groups (Supplementary Fig. 3B).

Given that allergic reactions are characterized not only by eosinophil infiltration but also by T helper type 2 (Th2) immune responses, we further employed an in vitro RBD peptide library stimulation method to assess the presence of RBD-specific Th2 cells. Lung cells were stimulated with the RBD peptide library for 6 hours, followed by intracellular cytokine staining and flow cytometric detection of CD3⁺CD4⁺IL-4⁺ cells (Supplementary Fig. 3C). No significant difference in pulmonary Th2 cell frequency was observed between groups (Supplementary Fig. 3D), suggesting that intranasal 4RBD-Fc did not trigger a Th2-skewed immune response. These findings demonstrate that intranasal administration of 4RBD-Fc did not induce pulmonary inflammation, allergic reactions, or systemic toxicity in vivo.

Prophylactic and therapeutic effects of i.n. administered 4RBD-Fc in SARS-CoV-2-infected mice

To assess the antiviral activity of 4RBD-Fc as a preventive or therapeutic treatment for SARS-CoV-2, we administered 4RBD-Fc (1 mg i.n.) or the PBS vehicle control to K18-hACE2 mice at either 2 hours before (PrEP group) or 24 or 48 hours after (PEP group) infection with the SARS-CoV-2 Delta strain with 4 × 10³ plaque-forming units (PFU) per mouse (Fig. 2F), as a well-established infection system³². At 5 days post-infection (dpi), significant weight loss (21.5%) was observed in the vehicle group, with all animals being euthanized by 5 dpi (a ≥ 15% loss of body weight compared to baseline was considered as the humane endpoint) (Fig. 2G). In contrast, all mice in the PrEP group and 66.7% (4/6) of the mice in the PEP group survived at 5 days post-infection (dpi). Both PrEP and PEP groups showed markedly lower viral loads in the upper respiratory tract (lower than LOD in PrEP, 2.8 × 10³ copies/ml in PEP versus 8.3 × 10⁴ copies/ml in vehicle controls) and lower respiratory tract (lower than LOD in PrEP, 3.1 × 10⁴ copies/ml in PEP versus 8 × 10⁷ copies/ml in vehicle controls), as confirmed by viral titer assays of throat swabs and lung tissues. Complete viral clearance (viral load < limit of detection: 1 × 10³ copies/ml) was achieved in 66.7% (2/3) of the PrEP group (Fig. 2H, I). These results thus supported that 4RBD-Fc administration could effectively reduce viral load of the SARS-CoV-2 Delta variant in vivo.

Given these findings, we next evaluated whether 4RBD-Fc affected transmission of SARS-CoV-2. Index mice, infected with the Delta strain at 4 × 10⁴ PFU, ten-fold higher than lethal concentrations, were co-housed with contact mice treated with 4RBD-Fc or PBS vehicle. By 5 dpi, all index mice succumbed, whereas none died in the contact groups (Fig. 2J). Viral titer assays indicated that vehicle-treated contact mice had obvious accumulation of viral loads (8 × 10³ copies/ml in throat swabs and 2.6 × 10⁴ copies/ml in lungs at 5 dpi) following contact with the index group (Fig. 2K), whereas no virus (below limit of detection) was detected in the 4RBD-Fc contact group by 5 dpi. These data were consistent with viral titer assays from throat swabs and lung tissue samples by 5 dpi (Fig. 2K, L). However, we observed detectable viral titers in the throat swabs of one mouse in the 4RBD-Fc contact group at both 1 dpi and 3 dpi.

Histopathological examination of the vehicle controls and index groups revealed diffuse hemorrhage, severe alveolar thickening, and bronchiole structure loss, indicative of fatal pneumonia progression, whereas only mild alveolar thickening was noted in the vehicle-treated contact groups (Supplementary Fig. 4A). Notably, no lung lesions were observed in the PrEP and 4RBD-Fc-treated contact groups. Altogether, these results advocate for the potential of i.n. delivered 4RBD-Fc as both prophylactic and therapeutic agent against SARS-CoV-2 infection and transmission.

Activation of anti-RBD de novo immune responses in respiratory-associated lymphoid tissues via i.n. administration of unadjuvanted 4RBD-Fc

Next, we examined the ability of 4RBD-Fc to drain to lymph nodes after i.n. administration. We assessed the distribution of 4RBD-Fc-AF750 in secondary lymphoid organs of K18-hACE2 mice (Fig. 3A). After 1 mg 4RBD-Fc-AF750 i.n. administration, 4RBD-Fc rapidly drained to respiratory-associated lymphoid tissues such as nasal-associated lymphoid tissues (NALT), mandibular lymph nodes (maLN), and mediastinal lymph nodes (mdLN) (Fig. 3B, C), but not to other secondary lymphoid tissues at early time points (Supplementary Fig. 4A–C). The 4RBD-Fc-AF750 signal in lymphoid tissues progressively rose, showing a 15.7-fold (NALT), 22.7-fold (maLN), and 12.6-fold (mdLN) increase by 96 hours, and a 17.2-fold (NALT), 60.1-fold (maLN), and 41.7-fold (mdLN) increase by 168 hours compared to 48 hours, indicating active accumulation of 4RBD-Fc in respiratory-associated lymphoid tissues by 96 hours (Fig. 3B). In addition, at 96 and 168 hours post-administration, weak but detectable 4RBD-Fc signals were also observed in other secondary lymphoid organs, suggesting limited dissemination beyond the respiratory-associated lymphoid tissues at later stages.

We further validated whether 4RBD-Fc draining to respiratory-associated lymphoid tissues could activate local immune responses, including innate and adaptive immunity. We i.n. administered 1 mg of 4RBD-Fc to a group of C57BL/6 mice and collected serum and mdLN at 0, 12, 48, 96, and 168 hours for analysis (Fig. 3D). By 168 hours post-administration, anti-RBD IgG antibodies became detectable in the serum of these mice at a titer of 9.3 × 10² using ELISA (Fig. 3F). Since the activation of B cell responses involves the expansion and differentiation of antigen-specific B cells, we used fluorescence-labeled RBD tetramers and flow cytometry to detect RBD⁺ B cells in mdLN (Fig. 3E, G). Robust RBD⁺ B cell expansion was detected at 168 hours in mdLN (Fig. 3G), characterized by significant increases in both proportions (1.2% versus 0.05%) and numbers (2 × 10⁴ versus 2 × 10²) of RBD⁺ B cells (Fig. 3G, H). Through further B cell phenotypic analysis, we observed differentiation in these RBD⁺ B cells. The proportion of Naive B cells (Naive, CD38⁺IgD⁺) significantly decreased among RBD⁺ B cells at 168 hours (95.2% at 96 hours versus 15.7% at 168 hours). Concurrently, the proportion of Memory B cells (Bmem, CD38⁺IgD^–) in RBD⁺ B cells increased at 96 hours (0% at 48 hours versus 4.1% at 96 hours), and germinal center B cells (GC, CD38^–IgD^–) appeared at 168 hours (0% at 96 hours versus 78.9% at 168 hours), suggesting differentiation of RBD⁺ Naïve B cells into GC and Bmem (Fig. 3I). These data indicate that i.n. administration of 4RBD-Fc triggered an RBD-specific B cell response in mdLN.

To assess the longevity of the anti-RBD immune response elicited by a single intranasal dose of 4RBD-Fc (1 mg, no adjuvant), we measured serum IgG endpoint titers at Days 14, 28, 42 and 56 post-administrations (Fig. 3E). Titers at Day 42 showed less than a 20% decline versus Day 14, indicating sustained antibody production. Consistently, serum collected at Day 42 exhibited pseudovirus IC₅₀ values statistically indistinguishable from those at Day 14 (Supplementary Fig. 7F), demonstrating persistent functional neutralization capacity. These findings suggest that, although additional long-term follow-up is needed to fully confirm durability, the neutralizing antibody activity remains effective at least up to Day 42 post-immunization, providing evidence for lasting antiviral protection.

To better understand 4RBD-Fc elicited immunity, we investigated the dynamic changes of immune cell subsets within these draining lymph nodes using flow cytometry, including dendritic cells (DCs), and antigen-specific T and B cells. Migratory DCs (tDCs) have been demonstrated to actively collect respiratory antigens and initiate adaptive immunity in mdLN^33,34. In mdLN, a cohort of tDCs was the first to respond to i.n. 4RBD-Fc, showing a significant increase at 48 hours post-administration (2.3 × 10² at 0 hour versus 1.3 × 10³ at 48 hours) (Fig. 3J). By 96 hours, lymph node cells stimulated with an RBD peptide library exhibited a marked increase in IFN-γ⁺CD4⁺ (0.06% at 0 hour versus 0.32% at 96 hours) and IFN-γ⁺CD8⁺ T cells (0.06% at 0 hour versus 1.25% at 96 hours), indicating the initiation of a Th1-biased RBD-specific cellular immunity (Fig. 3K). Similar RBD-specific B cell responses were observed in NALT and maLN, but not in the lungs (Supplementary Fig. 6A–F). Together, these findings provide cellular-level evidence that i.n. administration of 4RBD-Fc activates RBD-specific immunity in respiratory-associated lymphoid tissues.

Requirement of both Fc-fusion and antigen dosage for adjuvant-free mucosal immunogenicity of 4RBD-Fc

Typically, protein antigens require adjuvants to activate mucosal immunity^23,35,36. However, the antiviral formulation of 4RBD-Fc demonstrates the ability to achieve mucosal immune activation without adjuvants, which may attribute to its unique structure or dosage. To investigate the mechanism of this adjuvant-free immune activation, we administered 4RBD-Fc or 3RBD—which is also multimeric but lacks Fc-fusion—at low (lo, 20 μg) or high doses (hi, 1 mg) via i.n. administration in C57BL/6 mice, all without adjuvants. While the mock group received an equal volume of PBS (Fig. 4A). ELISA analysis of mice serum at day 7 revealed that anti-RBD IgG antibodies in the 4RBD-Fc (hi) group has an average titer of 2.5 × 10³. Conversely, only 25% (1/4) of mice in 3RBD (lo) and 3RBD (hi) groups showed detectable anti-RBD antibodies at a much lower titer of 1 × 10² (Fig. 4B). These results demonstrated effective anti-RBD antibody response could only be achieved in the 4RBD-Fc (hi) group. Flow cytometry analysis of RBD-specific B cells in 4RBD-Fc (hi) group revealed an RBD-specific GC response and B cell differentiation, marked by an increase in percentages and numbers of RBD⁺ B cell (Fig. 4C, D), a decrease in naive B cells (98.1% versus 28.1%), and an increase in GC B cells (0% versus 60%) and Bmem (0.6% versus 5.9%) (Fig. 4E) in mdLN. Meanwhile, only a notably higher frequencies of RBD peptide reactive IFN-γ⁺CD4⁺ and IFN-γ⁺CD8⁺ T cells were observed in the 4RBD-Fc (hi) group, compared to all other groups (Fig. 4F, G). Consistently, DC subsets in mdLN were also significantly elevated in the 4RBD-Fc (hi) group (Fig. 4H). This indicating that RBD-specific T cell response are exclusively generated in the 4RBD-Fc hi group. Together, these results suggest that both Fc-fusion and high antigen dosage contribute to the adjuvant-free mucosal immunogenicity of 4RBD-Fc in mice.

Enhanced systemic and mucosal immunity induced by the antiviral formulation of 4RBD-Fc compared to the vaccine formulation

To assess whether the immune response elicited by the antiviral drug formulation of 4RBD-Fc is sufficient to provide viral protection, we first compared it to the immune response induced by a validated mucosal vaccine formulation^23,37,38,39. By Fc-fused protein antigens to target the FcRn receptors expressed on respiratory epithelial cells, mucosal vaccines facilitate the crossing of antigens through the mucosal barrier and activate mucosal immunity in the presence of adjuvants^23,24,39. Since human IgG1-Fc can bind to murine FcRn with similar affinity²⁴, the 4RBD-Fc construct meets this criterion. Therefore, we developed a mucosal vaccine formulation of 4RBD-Fc (20 μg with CpG adjuvant) and compared the systemic and mucosal immune responses it induced to those triggered by the antiviral drug formulation (1 mg 4RBD-Fc without adjuvant), while the mock group received 20 μg CpG i.n. only (Fig. 5A). Following twice i.n. administration in C57BL/6 mice, both formulations induced respiratory mucosal immunity (Fig. 5B–J), including lung-resident memory B cells (BRMs) (Fig. 5B, H), mucosal antibodies in bronchoalveolar lavage (BAL) (Fig. 5D), GC responses in mdLN (Fig. 5G) and T cells in the lungs (Fig. 5I, J). Notably, the antiviral formulation demonstrated a rapid antibody production, with anti-RBD IgG antibodies detectable in serum by day 7 (6.3 × 10³), and consistently surpassed the vaccine formulation at subsequent time points (1.6 × 10⁴ versus 1.3 × 10³ at day 14, 6.3 × 10⁵ versus 3.2 × 10⁴ at day 28) (Fig. 5C). Of note, the antiviral formulation induced 10-fold higher mucosal IgG antibodies titer in BAL (9.2 × 10³) compared to the vaccine formulation (9.3 × 10²) (Fig. 5D, E). At day 28, serum from mice treated with antiviral formulation showed neutralizing activity against WT SARS-CoV-2 pseudovirus (IC₅₀ = 4716), while the vaccine formulation did not exhibit detectable neutralizing activity (IC₅₀ not determined) (Fig. 5F). Flow cytometry analysis revealed that antiviral formulation induced significant more RBD⁺ GC B cells in mdLN (2.1 × 10³ versus 3.6 × 10²) (Fig. 5G). To distinguish lung-resident B cells from circulating B cells, anti-CD45-APC antibody was administered intravenously (i.v.) to label circulating immune cells⁴⁰. Cells that were CD19⁺CD45i.v.^–CD38⁺IgD^– were considered to be lung-resident memory B cells⁴¹. The antiviral formulation (1.3 × 10³) elicited 8.9-fold more RBD⁺ BRMs than the vaccine formulation (1.5 × 10²) in the lungs (Fig. 5H). Both formulations induced more RBD-specific T cells in the lungs comparing to the mock group, including IL-2⁺ and TNF-α⁺CD4⁺ (Fig. 5I) and TNF-α⁺CD8⁺ T cells (Fig. 5J), detected via RBD peptide library stimulation and intracellular cytokine staining. Together, these data demonstrated that when administered intranasally, the antiviral 4RBD-Fc formulation elicits a stronger mucosal and systemic immune response than the vaccine formulation, while the vaccine formulation remains effective via intramuscular administration.

4RBD-Fc antiviral formulation outperforms vaccine formulation in providing immediate and sustained protection against SARS-CoV-2 variant

We postulated that the antiviral formulation of 4RBD-Fc would not only protect mice from imminent infection, as demonstrated in Fig. 2, but also offer sustained protection through its rapid and strong vaccine-like immune activation effect. As such, we compared the protectivity of 4RBD-Fc in antiviral formulation with vaccine formulation against SARS-COV-2 challenge (Fig. 6A). The vaccine group of K18-hACE2 mice was primed with 20 μg 4RBD-Fc adjuvanted with CpG i.n. at day 0, followed by two subsequent boosters at day 14 and day 42, then exposed to a lethal dose of SARS-CoV-2 Delta strain (4 × 10³ PFU) at day 63. Equal volume of PBS containing CpG i.n. was used as mock treatments. The antiviral group of K18-hACE2 mice received a single dose of 1 mg 4RBD-Fc i.n. at day 0 and were exposed to one lethal dose of SARS-CoV-2 Delta strain (4 × 10³ PFU) either at day 7 (D7) or day 14 (D14), or twice at both day 0 and day 14 (D7 + D14) (Fig. 6A). Both formulations effectively shielded K18-hACE2 mice from lethal Delta strain exposures, contrasting with the CpG i.n. group: 16.9% body weight loss and succumbed by 5 dpi (Fig. 6B). Remarkably, the antiviral formulation group, challenged with the Delta strain on either day 7 or day 14 post-administration, maintained stable body weights (100.4-100.7% of starting weight) (Fig. 6B) and exhibited significantly reduced respiratory viral loads (79-fold reduction in throat swaps and 398-fold in lungs) compared to the CpG i.n. group (Fig. 6C, D). Of note, even after two lethal challenges with the Delta strain on Day 0 and Day 14, mice receiving a single dose of the antiviral formulation survived and maintained stable body weights (105% of starting weight) (Fig. 6B). Compared to the CpG i.n. group, these mice exhibited a significant reduction in viral loads in both the upper (1.5 × 10⁵ versus 1.2 × 10³ copies/ml) and lower (2.7 × 10⁶ versus 9 × 10³ copies/ml) respiratory tracts (Fig. 6C, D). Given the amount of 4RBD-Fc in the lung was decreased by 50.4-fold at 168 hours post-administration (Fig. 2B), these results suggested that the protective effect of antiviral formulation, initially derived from hACE2 blockade, and followed by the activation and presence of anti-RBD immunity.

Both formulations of 4RBD-Fc markedly curtailed viral replication in throat swabs and lungs (Fig. 6C, D). The pulmonary virus titer assay showed a significant reduction in mice administered with i.n. vaccine formulations (21-fold), compared to the mock groups. However, a greater reduction was observed in those given the antiviral formulation: 735-fold in the D7 group, 191-fold in the D14 group, and 274-fold in the D0 + D14 group, compared to the CpG i.n. group. These data demonstrated that a single dose of antiviral formulation outperformed three rounds of vaccine formulations in reducing viral load in the lower respiratory tract for a sustained period of at least two weeks.

In conclusion, these results demonstrate that the immune responses activated by 4RBD-Fc are sufficient to protect mice from lethal doses of SARS-CoV-2 infection. Moreover, the antiviral formulations of 4RBD-Fc offer superior protection to the lungs compared to vaccine formulations. Particularly, the dual benefits of immediate hACE2 blocking effects and the subsequent development of anti-RBD immunity can be attained with just a single dose of the antiviral formulation of 4RBD-Fc.

Lower dose 4RBD-Fc maintains respiratory tract retention and induces anti-RBD immune responses

To further assess the optimal therapeutic dose of i.n. 4RBD-Fc, we conducted biodistribution and immunogenicity studies using lower doses (50 μg and 200 μg). In vivo imaging and ex vivo organ analysis on day 7 post-administration showed that mice receiving 200 μg of 4RBD-Fc-AF750 retained a greater fluorescent signal in the respiratory tract (nasal cavity and lungs) compared to the 50 μg group (Supplementary Fig. 7A–C). Moreover, lower background signal was observed in peripheral organs in the 200 μg group relative to the original 1 mg dose used in earlier experiments, indicating improved respiratory specificity at the reduced dose.

To determine whether these lower doses could still elicit an immune response, we measured serum anti-RBD IgG titers at day 7 following intranasal administration of unadjuvanted 4RBD-Fc. We found that 200 μg, but not 50 μg, was sufficient to induce a robust antibody response (Supplementary Fig. 7D, F). These results support the use of 200 μg as an effective and respiratory-specific intranasal dose that maintains both local retention and immunogenic potential.

Scientists have uncovered the world’s oldest evidence of human-Neanderthal interbreeding: a 140,000-year-old child from Israel’s Skhul Cave.

The fossil shows a unique blend of traits, revealing that humans and Neanderthals were mixing tens of thousands of years earlier than once believed.

Fossil Discovery Challenges Human Evolution Timeline

An international team of researchers from Tel Aviv University and the French National Centre for Scientific Research has uncovered the earliest proof that Neanderthals and Homo sapiens formed close connections, both socially and biologically, in what is now Israel.

Their study centers on the skeleton of a five-year-old child unearthed nearly a century ago in the Skhul Cave on Mount Carmel. Dating back around 140,000 years, the fossil is the oldest known example of a human exhibiting a mix of traits from both Neanderthals and Homo sapiens. For decades, these groups were considered entirely separate species.

The project was led by Prof. Israel Hershkovitz of Tel Aviv University’s Gray Faculty of Medical and Health Sciences and Anne Dambricourt-Malassé of the French National Centre for Scientific Research. The results were published in the journal l’Anthropologie.

Earliest Evidence of Human Hybrid Traits

According to the research team, “This discovery reveals the world’s earliest known human fossil showing morphological traits of both of these human groups, which until recently were considered two separate human species. The current study shows that the five-year-old child’s skeleton is the result of continuous genetic infiltration from the local—and older—Neanderthal population into the Homo sapiens population.”

An international study led by researchers from Tel Aviv University and the French National Centre for Scientific Research provides the first scientific evidence that Neanderthals and Homo sapiens had biological and social relations, and even interbred for the first time, in the Land of Israel.

DNA Links Between Neanderthals and Homo sapiens

“Genetic studies over the past decade have shown that these two groups exchanged genes,” explains Prof. Hershkovitz. “Even today, 40,000 years after the last Neanderthals disappeared, part of our genome—2 to 6 percent—is of Neanderthal origin. But these gene exchanges took place much later, between 60,000 to 40,000 years ago.

“Here, we are dealing with a human fossil that is 140,000 years old. In our study, we show that the child’s skull, which in its overall shape resembles that of Homo sapiens—especially in the curvature of the skull vault—has an intracranial blood supply system, a lower jaw, and an inner ear structure typical of Neanderthals.”

Neanderthals in the Levant: A Much Deeper History

For years, Neanderthals were thought to be a group that evolved in Europe, migrating to the Land of Israel only about 70,000 years ago, following the advance of European glaciers. In a groundbreaking 2021 study published in the prestigious journal Science, Prof. Hershkovitz and his colleagues showed that early Neanderthals lived in the Land of Israel as early as 400,000 years ago.

This human type, which Prof. Hershkovitz called “Nesher Ramla Homo” (after the archaeological site near the Nesher Ramla factory where it was found), encountered Homo sapiens groups that began leaving Africa about 200,000 years ago—and, according to the current study’s findings, interbred with them.

The child from the Skhul Cave is the earliest fossil evidence in the world of the social and biological ties forged between these two populations over thousands of years. The local Neanderthals eventually disappeared when they were absorbed into the Homo sapiens population, much like the later European Neanderthals.

Cutting-Edge Technology Unlocks Ancient Secrets

The researchers reached these conclusions after conducting a series of advanced tests on the fossil. First, they scanned the skull and jaw using micro-CT technology at the Shmunis Family Anthropology Institute at Tel Aviv University, creating an accurate three-dimensional model from the scans.

This enabled them to perform a complex morphological analysis of the anatomical structures (including non-visible structures such as the inner ear) and compare them to various hominid populations. To study the structure of the blood vessels surrounding the brain, they also created an accurate 3D reconstruction of the inside of the skull.

The Skhul Child: The World’s Oldest Human-Neanderthal Hybrid

“The fossil we studied is the earliest known physical evidence of mating between Neanderthals and Homo sapiens,” says Prof. Hershkovitz. “In 1998, a skeleton of a child was discovered in Portugal that showed traits of both of these human groups. But that skeleton, nicknamed the ‘Lapedo Valley Child,’ dates back to 28,000 years ago—more than 100,000 years after the Skhul child.

“Traditionally, anthropologists have attributed the fossils discovered in the Skhul Cave, along with fossils from the Qafzeh Cave near Nazareth, to an early group of Homo sapiens. The current study reveals that at least some of the fossils from the Skhul Cave are the result of continuous genetic infiltration from the local—and older—Neanderthal population into the Homo sapiens population.”

Reference: “A new analysis of the neurocranium and mandible of the Skhūl I child: Taxonomic conclusions and cultural implications” by Bastien Bouvier, Anne Dambricourt Malassé, Marcel Otte, Michael Levitzky and Israël Hershkovitz, 14 June 2025, L’Anthropologie.
DOI: 10.1016/j.anthro.2025.103385

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Major depressive disorder (MDD) is one of the most common psychiatric illnesses worldwide, but its molecular causes have still not been clearly identified. A domestic research team has discovered that depression may not simply be caused by neuronal damage, but can also arise from the dysregulation of specific neural signaling pathways. In particular, they identified the molecular reason why elderly patients with depression do not respond to conventional antidepressants. This study suggests the possibility of therapeutic approaches using optogenetic technology to regulate neural signaling, and it provides clues for the development of new treatment strategies targeting the protein ‘Numb’ protein for elderly patients with depression.

KAIST (President Kwang Hyung Lee) announced on the 19th of August that a research team led by Distinguished Professor Won Do Heo of the Department of Biological Sciences at KAIST, in collaboration with forensic pathologist Minju Lee of the National Forensic Service (Director Bong Woo Lee) and Professor Seokhwi Kim of the Department of Pathology at Ajou University Medical Center (Director Sangwook Han), identified a new molecular mechanism for depression through RNA sequencing and the immunohistochemical analysis of brain tissue from patients who had committed suicide. Furthermore, they demonstrated in animal models that antidepressant effects can be restored by regulating the signaling pathway that induces neural recovery using optogenetic technology.

The research team focused on the hippocampus, the brain region responsible for memory and emotion, and in particular on the dentate gyrus (DG). The DG is the entry point of information into the hippocampus, playing a role in new memory formation, neurogenesis, and emotional regulation, and is closely linked with depression.

Using two representative mouse models for depression (the corticosterone stress model and the chronic unpredictable stress model), the team found that stress induced a striking increase in the signaling receptor FGFR1 (Fibroblast Growth Factor Receptor 1) in the DG. FGFR1 receives growth factor (FGF) signals and transmits growth and differentiation commands within cells.

Subsequently, using conditional knockout (cKO) mice in which the FGFR1 gene was deleted, the researchers revealed that the absence of FGFR1 made mice more vulnerable to stress and led them to exhibit depressive symptoms more quickly. This indicates that FGFR1 plays a critical role in proper neural regulation and stress resistance.

The team then developed an ‘optoFGFR1 system’ using optogenetics, enabling FGFR1 —essential for stress resistance—to be activated by light. They observed that activating FGFR1 in depression mouse models lacking FGFR1 restored antidepressant effects. In other words, they experimentally demonstrated that the activation of FGFR1 signaling alone could improve depressive behavior.

Surprisingly, however, in aged depression mouse models, the activation of FGFR1 signaling through the optoFGFR1 system did not yield antidepressant effects. Investigating further, the researchers found that in the aged brains, a protein called ‘Numb’ was excessively expressed and interfered with FGFR1 signaling.

Indeed, analysis of postmortem human brain tissue also showed the specific overexpression of Numb protein only in elderly patients with depression. When the researchers suppressed Numb using a gene regulatory tool (shRNA) while simultaneously activating FGFR1 signaling in mouse models, neurogenesis and behavior—previously unrecoverable—returned to normal even in aged depression models. This shows that the Numb protein acts as a “blocker” of FGFR1 signaling and is a key factor preventing the hippocampus from executing antidepressant mechanisms.

This study is meaningful in that it revealed that depression may not only result from simple neuronal damage, but can also arise from the dysregulation of specific neural signaling pathways. In particular, we identified the molecular reason why antidepressants are less effective in elderly patients, and we expect this to provide a clue for the development of new therapeutic strategies targeting the Numb protein.”

Won Do Heo, Distinguished Professor of KAIST

He added, “Moreover, this interdisciplinary study, which combined KAIST’s expertise in neuroscience with the National Forensic Service’s forensic brain analysis technologies, is expected to serve as a bridge between basic research on psychiatric disorders and clinical applications.”

This study, led by first author Jongpil Shin, a PhD student in the Department of Biological Sciences at KAIST, was published on August 15, 2025, in the international journal Experimental & Molecular Medicine.

Opinion by: Sasha Shilina, founder of Episteme and researcher at Paradigm Research Institute

In 2024, Nature reported a record-breaking number of scientific paper retractions: over 10,000 papers pulled from journals due to fraud, duplication or flawed methodology. Peer review, the long-revered backbone of academic legitimacy, is under siege. It’s too slow, too opaque and too easily gamed.

Meanwhile, artificial intelligence models trained on this flawed data set generate confident but nonsensical output. Papers cite nonexistent studies. Research decisions are guided by influence, not inference. The internet, once hailed as a democratizing force for knowledge, is now a battleground of misinformation, clickbait and manipulated metrics.

We are living in an epistemic crisis.

And yet, buried in the unlikely corners of Crypto X and decentralized autonomous organization (DAO) forums, a new architecture is forming. Not for transferring value, but for verifying truth.

A layer 2 for knowledge

In the crypto world, layer 2s address the scalability issue. They help Ethereum process more transactions faster and cheaper. But what if the real scalability bottleneck isn’t financial — it’s epistemological?

Science isn’t scaling. Reputation hierarchies, legacy journals and funding gatekeepers bottleneck it. Brilliant hypotheses die in grant purgatory. Replications go unrewarded. Errors take years to correct, if ever.

What does a “layer 2 for truth” actually look like? This system transforms scientific hypotheses into onchain objects, public, persistent and open to scrutiny. Instead of broadcasting belief on social media, participants stake it, putting skin in the game and exposing their convictions to real risk. Resolution becomes a hybrid process: AI models parse and score evidence, human validators contest or affirm outcomes, and decentralized oracles record the result transparently. Crucially, incentives shift away from prestige and toward precision, rewarding those who are right, not just well-positioned.

This is not decentralized finance (DeFi). It’s not even decentralized science (DeSci). It’s agentic, decentralized science (DeScAI). More radically, however, it’s epistemic finance: Markets built not around coins but claims.

Betting on reality

This isn’t just science gambling. It’s a structural inversion. Today, the academic economy rewards being interesting, not correct. Flashy papers get media attention and grant renewals, whether or not their findings replicate. Meanwhile, replication studies, null results and quiet work often vanish.

Prediction markets can flip the script. They pay you to be right. Not to be loud, famous or institutionally blessed, but simply correct about the world. If a biotech researcher predicts that a particular compound will reduce tumor growth by 20% in mice, and they’re right, they win. If they’re wrong, they lose. Simple. Transparent. Brutally honest.

In this model, belief becomes a measurable asset. Knowledge becomes liquid. The marketplace doesn’t just trade tokens; it trades epistemic confidence.

The oracle problem reimagined

In crypto, the “oracle problem” is getting real-world data onto the blockchain trustlessly. In this epistemic architecture, the oracle isn’t just a price feed. It mediates what is accepted as truth.

Related: Crypto policy trends to watch in 2025: Privacy, development and adoption

This raises uncomfortable questions: Who gets to decide what’s true? Can AI serve as a reliable resolver? What happens when markets are wrong?

The answer is that there’s no singular oracle. There’s a protocol. Resolution becomes a process: part-automated, part-contested and part-historical. Participants challenge, update and refine claims. Truth becomes iterative, open-source and adversarial, like code.

Yes, this opens the door to epistemic volatility. In a world where even Nobel laureates get it wrong, isn’t volatility better than stagnation?

From publishing to protocols

The internet disrupted publishing. Blockchains disrupted finance. Now, a third disruption is underway: the protocolization of knowledge.

In this emerging paradigm, the architecture of knowledge itself is being reimagined. Papers are no longer static PDFs but dynamic contracts embedded with predictive weight, designed to inform and be tested. Citations become more than scholarly gestures; they’re transformed into onchain links annotated with confidence scores and traceable influence. Once a closed gatekeeping ritual, peer review evolves into an open, adversarial verification market where claims can be challenged, revised and resolved in public view. 

In this model, science stops being a static archive and becomes an economic, dynamic and plural living system.

Truth is the next asset class

We’ve priced money, time and attention. We’ve never truly priced belief. Not until now.

A new kind of market emerges, one that doesn’t reward speculation but verification — a civic instrument for aligning incentives around truth in an age of noise. The question isn’t whether these markets are risky. All markets are. The question is: Can we afford not to try?

If crypto is a new internet, we need more than memes, memecoins and monkey JPEGs. We need infrastructure for the next epistemic era: for validating what matters, when it matters, in public.

The next big layer isn’t for money. It’s for the truth.

Opinion by: Sasha Shilina, founder of Episteme and researcher at Paradigm Research Institute.

This article is for general information purposes and is not intended to be and should not be taken as legal or investment advice. The views, thoughts, and opinions expressed here are the author’s alone and do not necessarily reflect or represent the views and opinions of Cointelegraph.