Biology subjects

Chen, X. Y.

Publications and source records attributed to Chen, X. Y..

4 recordsLinked to original sources

bioRxiv2026

Serial intravascular labeling resolves dynamic decidual NK residency and gestational remodeling toward T-bet-Low states

Decidual natural killer (dNK) cells are the predominant immune population at the maternal-fetal interface during early pregnancy. However, how vascular trafficking, tissue residency, proliferation, and apoptosis-associated activity are coordinated to establish and maintain the dNK population throughout pregnancy remains unclear. We hypothesized that gestational remodeling of the dNK compartment reflects coordinated changes in these cellular processes in association with progressive T-bet downregulation. We combined serial intravascular labeling (SIVL), flow cytometry, BrdU incorporation, active caspase-3 detection, spatial imaging, and Tbx21 fate mapping to examine NK cells in virgin mice and across gestation. Pregnancy altered CD49a/CD49b-defined dNK-cell composition and redistributed dNK cells among SIVL-defined vascular-accessibility states, supporting a model of dynamic dNK-cell tissue residency. Trafficking-associated marker scores displayed continuous gradients of tissue retention, circulatory/egress potential, and chemokine responsiveness rather than defining a single resident state. Spatial imaging demonstrated greater dNK-cell density in the mesometrial decidua and preferential CD31 vessel contact by recently intravascular dNK cells during early and mid-gestation. BrdU incorporation and active caspase-3 positivity peaked during early pregnancy and varied across SIVL-defined states. Tbx21 fate mapping identified a progressive and selective shift from current T-bet expression toward ex-T-bet and non-fate-mapped Eomes dNK states. T-bet-low states preferentially maintained proliferation at mid-gestation, whereas current T-bet expression was associated with greater circulatory/egress potential. However, active caspase-3 was not selectively increased in current T-bet-expressing cells. Collectively, these findings identify pregnancy-induced dNK-cell remodeling as a coordinated process integrating dynamic tissue residency, vascular accessibility, local proliferation, and apoptosis-associated activity, alongside a progressive shift toward T-bet-low dNK states.

immunology↗

bioRxiv2025

National Scale Genomic Engine for Precision Medicine: Singapore PRECISE-SG100K Experience

The whole-of-nation National Precision Medicine (NPM) programme in Singapore aims to integrate a genomics backbone into standard healthcare. Phase II recently completed the sequencing of 102,202 genomes from the diverse Asian population of Singapore, generating the PRECISE-SG100K dataset. The scaling from the pilot SG10K_Health phase to national production scale demanded a central shift: from earlier generation workflows to an integrated, industrial grade "Genomic Engine". The initiative was co-developed under a public-private partnership model. Our Genomic Engine was designed with an automation-first approach, as a modular platform linking a purpose-built, centralized biospecimen processing and DNA extraction facility (EXTRACT Lab), a high-throughput sequencing operation (Illumina Data Generation Infrastructure, IDGI), with the cloud-native analytics (GRIDS) running on a fully integrated PRECISE Sample Tracking System (STS). Here we describe the key design features of our Genomic Engine. Highlighting the Stress Test phase where the automated DNA extraction yields failed to meet expectations. We share the operational adjustments which were implemented to stabilize production and resulted in a three-fold reduction in sample triage due to improved DNA recovery. Without establishing the operational guardrails during the Stress Test, the Engine would not have reached a steady-state production evidenced by >3,000 genomes per month, median turnaround time 11 days, 99.6% operational success, within in six months. This framework offers a practical blueprint for other population-scale initiatives seeking to bridge the gap between scientific piloting and industrial delivery.

genomics↗

bioRxiv2024

Soleus H-Reflex Up-Conditioning during Sciatic Nerve Regeneration in Rats Improves Recovery of Locomotion

Operant conditioning of the spinal stretch reflex or its electrical analog, the H-reflex, induces plasticity in the brain and spinal cord that increases (up-conditioning) or decreases (down-conditioning) the reflex elicited by primary afferent input to the spinal motoneuron. In rats in which the sciatic nerve is transected and repaired, soleus (SOL) H-reflex up-conditioning during regeneration strengthens primary afferent reinnervation of SOL motoneurons and improves recovery of the SOL H-reflex. This suggests that H-reflex up-conditioning could improve functional recovery after nerve injury and repair. To explore this possibility, we examined the impact of SOL H-reflex up- or down-conditioning during sciatic regeneration on recovery of locomotor symmetry. Sprague-Dawley rats were implanted with EMG electrodes in right SOL and a stimulating cuff on right posterior tibial nerve. After control data collection, right sciatic nerve was transected and repaired. Control EMG and H-reflex data collection continued for 20 more days. The rat was then exposed for 100 days to either: continued control data collection; SOL H-reflex up-conditioning; or SOL H-reflex down-conditioning. Locomotor EMG, H-reflex, and kinematics were assessed before nerve transection and 120 days after transection. H-reflex up-conditioning improved H-reflex recovery and also restored right/left step symmetry. H-reflex down-conditioning did not worsen H-reflex recovery or right/left step asymmetry. These results suggest that H-reflex up-conditioning might enhance functional recovery after nerve injury in humans. They also confirm previous results indicating that compensatory plasticity prevents inappropriate H-reflex conditioning (i.e., down-conditioning) from further impairing function.

neuroscience↗

bioRxiv2019

Kelch13 and MDR1 Polymorphisms, and Drug Effectiveness at Day 3 after Dihydroartemisinin-Piperaquine Treatment for Plasmodium falciparum Malaria on Bioko Island, Equatorial Guinea: 2014-2017

Artemisinin (ART) combination therapies were introduced on malaria endemic Bioko Island in 2004 through Bioko Island Malaria Control Project. Recently, ART-resistant Plasmodium falciparum strain with Kelch13 (K13) propeller M579I mutation originating from Equatorial Guinea was observed as an increased parasite clearance time on day 3 after dihydroartemisinin-Piperaquine (DHA-PIP) treatment (D3 positivity). Here, we surveyed DHA-PIP effectiveness and molecular markers of drug resistance at D3 after DHA-PIP treatment on Bioko Island from 2014 to 2017. Among the 371 uncomplicated P. falciparum patients, 86.3% (320/471) were successfully followed up at D3. 5.9% (19/320) of patients showed D3 positivity. K13 and MDR1 gene were successfully sequenced from 46 patients collected at D0 (baseline population) and 19 D3-positivity patients. Five non-synonymous K13 mutations (H136N; K189N; K248N; K326E; K332N) were found. There was no statistical difference in the frequency of these K13 mutations between baseline population and D3-positivity samples (p>0.05). Additionally, none of the K13 propeller polymorphisms known to be involved in ART-resistance in Asia or Africa were detected. For MDR1 gene, 38.5% (25/65) carried N86Y mutation; 73.8% (48/65) the Y184F mutation. Parasites surviving DHA-PIP at D3 post-treatment were significantly more likely than the baseline population to carry the N86Y (p <0.05). These results suggest that K13 is not the best predictive molecular marker for ART resistance in Africa. More isolates from cases with delayed parasite clearance after DHA-PIP treatment indicated that in vitro and in vivo monitoring for ART derivatives and ACT partner drugs should be regularly performed on Bioko Island, Equatorial Guinea.

epidemiology↗