Biology subjects

Che, W.

Publications and source records attributed to Che, W..

6 recordsLinked to original sources

bioRxiv2026

Circulating apoB-containing lipoproteins constituted blood-borne innate immune barrier limits ZIKV dissemination and congenital infection risk

Following establishment of primary viremia, flaviviruses require prompt penetration through vascular endothelium to achieve systemic dissemination, yet most infections remain asymptomatic or self-limited. Canonical defenses, including complement and phagocyte clearance, cannot fully explain this containment, suggesting an additional blood-borne antiviral barrier. Here, we identify apoB containing lipoproteins as potent restriction factors against Zika virus (ZIKV), a devastating danger of global pregnancy. By displaying surface accessible phosphatidylserine (PS), they competitively occupy host PS receptors and block entry by viruses exploiting apoptotic mimicry, including flaviviruses, Ebola, and chikungunya virus. In vivo, increasing apoB lipoproteins enhances serum antiviral activity and limits systemic ZIKV dissemination. This barrier extends to the maternal fetal interface, where elevated maternal LDL attenuates vertical transmission and fetal abnormalities. Its efficacy is modulated by gestational fluctuations in maternal LDL level and low abundance in fetal circulating LDL. Collectively, apoB containing lipoproteins form a constitutive blood-borne innate immune barrier that restrains apoptotic-mimicry viruses during the intravascular phase, limits viral dissemination and reduces congenital infection risk. This study provides a rationale for developing diet augmentation strategy to strengthen this innate barrier in at-risk individuals.

microbiology↗

bioRxiv2026

Widespread use of invalid statistical tests in biomedical machine learning

Cross-validation is routinely used to compare performance in biomedical artificial intelligence. Standard tests ignore correlation across cross-validation folds, inflating false-positive rates. In a PRISMA-guided meta-analysis of 184 studies (impact factor [≥] 15) across 30 biomedical fields, 97% use invalid tests. Among studies with abstract-level claims supported by invalid tests, 59% rely on a spurious comparison: one that loses significance after correcting for this correlation. On average, regaining significance requires a 43% larger effect. Extending these findings to the broader literature, we estimate that spurious comparisons occur in nearly two in three studies and support abstract-level claims in nearly one in three studies. Simulations confirm false-positive rates paradoxically approach 100% when cross-validation is repeated to improve stability. We introduce SHARP, a redesign of cross-validation, which best balances false-positive control and power among 13 benchmarked tests. These results reveal widespread fragility in biomedical artificial intelligence and offer a practical route to valid comparisons.

bioinformatics↗

bioRxiv2026

Bidirectional modulation of pain by neurofeedback: Preliminary findings with fMRI at 7T

Previous brain decoding studies indicate that an individuals pain experience can be robustly predicted from distributed patterns of brain activity. Two brain decoders have notably been associated respectively with the nociceptive and cognitive aspects of pain experience, the Neurologic Pain Signature (NPS) and the Stimulus-Intensity Independent Pain Signature (SIIPS). Yet, we still do not know if these brain patterns are also causally related to pain experience. To evaluate this possibility, we used high-field (7-Tesla) fMRI to test whether humans can alter their pain experience by bidirectionally modulating their pain-related brain activity in decoded neurofeedback paradigm. In a double-blind design, participants were trained to up- and down-regulate the NPS or the SIIPS. Our results indicate that participants can achieve bidirectional control of both signatures. NPS expression reliably increased during pain stimulation and covaried with both stimulus intensity and subjective ratings. In contrast, SIIPS expression did not show consistent stimulus-locked effects in the primary analyses. Importantly, reduction in pain rating was specific for SIIPS-training, whereas NPS has failed to show any consistent behavioral effect. Based on these preliminary findings, we hereby preregister a follow-up study, with specified rationale, hypotheses, experimental design, and analysis protocols.

neuroscience↗

bioRxiv2025

Working Memory Selectively Modulates Subjective Perception: A Pilot Study

The present study demonstrates a blindsight-like dissociation between subjective perception and general perceptual capacity in nonclinical observers. Participants performed either a two-interval forced-choice (2-IFC) or a Yes/No face detection task during working memory delay. To match general perceptual processing capacity across conditions, we titrated stimulus luminance contrast in the 2-IFC task and applied the same contrast in the Yes/No task. In Experiment 1, categorically incongruent (i.e., scene) information held in working memory impaired the sensitivity of the Yes/No detection of stimulus presence (face) vs. absence (blank background). In contrast, this effect was absent in Experiment 2, in which the Yes/No task required a discrimination of a face (target) vs. a scrambled face (non-target). These findings indicate that stimulus incongruency in working memory selectively influences subjective perception, dissociating it from general perceptual capacity.

neuroscience↗

bioRxiv2025

Stuck on you! Social brain stimulation increases the cognitive effort required to return to the egocentric perspective

Flexible switching between self and other perspectives is critical for adaptive social cognition and is thought to rely on the dynamic regulation of self-other representations. Although neuroimaging implicates the dorsomedial prefrontal cortex (dmPFC) and right temporoparietal junction (rTPJ) in perspective-taking, causal evidence for their specific contributions to perspective switching is lacking. Here, we applied focal transcranial direct current stimulation (f-tDCS) to the dmPFC and rTPJ while participants completed a visual perspective-taking task requiring switches between egocentric and altercentric viewpoints. Anodal stimulation to either site selectively increased the cognitive cost of switching back to the egocentric-perspective, without affecting switches into the altercentric-perspective. Rather than facilitating re-engagement with self-referential processing, stimulation enhanced altercentric persistence or impaired disengagement from the altercentric perspective. These findings provide novel causal evidence that both the dmPFC and rTPJ are involved in regulating the inhibition and updating of self-other representations during perspective switching. Results suggest that stimulation of these hubs may disrupt efficient realignment to the self, highlighting their role in maintaining an altercentric cognitive state. Future studies are required to uncover the precise neural computations that account for the comparable behavioural outcomes observed across distinct social brain hubs.

neuroscience↗

bioRxiv2023

What can we learn when fitting a complex gene expressionmodel to a simple telegraph model?

In experiments, the distributions of mRNA or protein numbers in single cells are often fitted to the random telegraph model which includes synthesis and decay of mRNA or protein, and switching of the gene between active and inactive states. While commonly used, this model does not describe how fluctuations are influenced by crucial biological mechanisms such as feedback regulation, non-exponential gene inactivation durations, and multiple gene activation pathways. Here we investigate the dynamical properties of four relatively complex gene expression models by fitting their steady-state mRNA or protein number distributions to the simple telegraph model. We show that despite the underlying complex biological mechanisms, the telegraph model with three effective parameters can accurately capture the steady-state gene product distributions, as well as the conditional distributions in the active gene state, of the complex models. Some effective parameters are reliable and can reflect realistic dynamic behaviors of the complex models, while others may deviate significantly from their real values in the complex models. The effective parameters can also be applied to characterize the capability for a complex model to exhibit multimodality. Using additional information such as single-cell data at multiple time points, we provide an effective method of distinguishing the complex models from the telegraph model. Furthermore, using measurements under varying experimental conditions, we show that fitting the mRNA or protein number distributions to the telegraph model may even reveal the underlying gene regulation mechanisms of the complex models. The effectiveness of these methods is confirmed by analysis of single-cell data for E. coli and mammalian cells. All these results are robust with respect to cooperative transcriptional regulation and extrinsic noise. In particular, we find that faster relaxation speed to the steady state results in more precise parameter inference under large extrinsic noise.

biophysics↗