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Jia, F.

Publications and source records attributed to Jia, F..

14 recordsLinked to original sources

Motor learning refines premotor cortical constraint during skilled forelimb behavior

Motor learning transforms variable actions into reliable skilled behavior, but how premotor cortex supports this transformation remains unclear. We longitudinally recorded bilateral local field potentials and single-unit activity from the rat rostral forelimb area while animals acquired a single-pellet retrieval task. Here, we show that improved skill was accompanied by reduced, rather than increased, task-related premotor recruitment. Despite this attenuation, firing remained dominated by suppression around pellet retrieval, and stronger pre-retrieval suppression was associated with greater odds of successful performance. Population neural state analysis further showed that successful actions were most strongly coupled to sustained pre-retrieval engagement early in learning, whereas later success occurred with less population-level engagement. These findings reveal premotor cortical constraint as a population-level process that is progressively refined as motor learning transforms variable actions into reliable skilled behavior.

neuroscience↗

Sialoglycans modulate Siglec-5 - TLR4 Interactions in Osteoarthritis

Osteoarthritis (OA) is characterized by chronic, low-grade inflammation that contributes to cartilage degradation and joint pain. We previously identified Siglec-5/14 in synovial fluid of OA patients (OA SF), which prompted us to investigate its interaction with the sialylated proinflammatory receptor TLR4 in monocytes. Here, we reveal an inverse correlation between Siglec-5 and TLR4, suggesting Siglec-5 may suppress inflammation. To gain mechanistic insights, monocytes stimulated with OA SFs were compared to M-CSF, LPS, and sialidase, to assess patient-specific inflammatory pathways and phenotypes. Notably, OA SF that triggered elevated IL-6 production in monocytes exhibited phenotypes similar to those of LPS- or sialidase-treated cells, reinforcing the role of sialylation patterns influencing OA severity. To confirm direct interaction of Siglec-5 and TLR4, colocalization was analyzed, displaying a time- and sialoglycan-dependent interaction. These findings reveal a Siglec-5-TLR4 axis modulated by sialylation, highlighting a potential strategy for mitigating inflammation and preserve joint integrity in OA.

immunology↗

China Autism Brain Imaging Consortium: Charting Brain Growth in Chinese Children with Autism

Autism Spectrum Disorder (ASD) is a lifelong neurodevelopmental condition characterized by atypical brain growth. While advances in neuroimaging and openly sharing large-sample datasets such as the Autism Brain Imaging Data Exchange (ABIDE) have improved understanding of ASD, most studies focus on adolescents and adults, with early brain development-critical for diagnosis and intervention-remaining underexplored. Existing research predominantly involves Western samples, offering limited insight and generalizability into non-Caucasian populations. We introduce the China Autism Brain Imaging Consortium (CABIC) (https://php.bdnilab.com/resources/), a grassroots effort by researchers across the country to aggregate previously collected multi-site structural MRI datasets and phenotypic information from 1,451 autistic children and 1,119 typically developing children, covering an age range from early childhood to school age (1.0 - 12.92 years). Here, we present this resource and depict brain growth charts to push forward a more comprehensive understanding of the brain development in Chinese autism children. We constructed brain growth charts that reveal a developmental shift in autistic children, transitioning from early overgrowth to delayed maturation. Regional analyses identified distinct atypical trajectories across specific brain regions. Individual deviation scores quantified inter-subject variability, characterizing the heterogeneity of brain development in ASD. Comparative analyses between CABIC and ABIDE highlighted differences potentially attributable to ethnicity and culture, advancing our understanding of cross-population neurodevelopmental diversity. CABIC MRI datasets will be shared publicly to foster investigation of the potential neural mechanisms underlying ASD in non-Western populations and support efforts toward precision medicine for autistic individuals across diverse backgrounds.

neuroscience↗

Role of Age in Mediating the Association Between the Vaginal Microbiota and Preterm Birth

The vaginal microbiota plays a crucial role in vaginal health and pregnancy outcomes. However, the influence of maternal characteristics, especially age, on the relationship between the vaginal microbiota and preterm birth is poorly understood. This study quantifies the effects of race, maternal age, and gestational age on vaginal microbiota composition. Our results demonstrate stronger associations between preterm birth and a less optimal vaginal microbiota in White and Asian women compared to Black or African American women. The microbiota difference between preterm and term births was more pronounced in older reproductive-age women, with Lactobacillus species increasing with age only in term births. Additionally, lower alpha diversity was observed in term pregnancies compared to preterm during both early and late pregnancy, particularly in women aged above 25 years. These findings highlight the mediating role of age in the relationship between the vaginal microbiota and preterm birth.

microbiology↗

Siglec-F Deficiency Prevents Fibrosis After Bleomycin-Induced Acute Lung Injury

Injury to the lungs causes acute inflammation that can lead to pathological lung fibrosis. Airspace macrophages (AMs) are critical for repair of injured tissue, but they can contribute fibrosis through mechanisms that are incompletely understood. Siglecs are expressed by immune cells. In mice, Siglec-F is chiefly expressed AMs where it is considered inflammosuppressive. We hypothesized that its deletion would worsen lung injury and fibrosis in response to intratracheal bleomycin challenge. We evaluated Siglec-F expression and function in mice challenged with bleomycin on days 7, 14, and 21 post-challenge (2.5 U/kg). AMs were the predominant inflammatory cells at all timepoints, and they included resident (RAM) and recruited (RecAM) subsets. Siglec-F deficiency prevented fibrosis than in Siglecf-/- mouse lungs, as evident from biochemical and histologic readouts. We performed RNAseq on pooled RAMs and RecAMs from wild type and Siglec-F deficient mice. Lung fibrosis 21 d after bleomycin challenge was associated with differentially expressed genes (DEGs) related to cholesterol synthesis and metabolism. In AMs from healthy lung lavage fluid and idiopathic pulmonary fibrosis patient tissues, the human paralogs Siglec-7 and Siglec-9 were expressed. Findings here identify novel mechanisms that control protective and detrimental functions of AMs after lung injury.

physiology↗

Platinum drug reprogramming of protein phosphorylation

Cisplatin is a DNA-targeting chemotherapeutic. Here we investigate how the cisplatin damaged gene loci are linked to specific protein-driven signalling pathways. Using forward chemical genetics methods, cisplatin damage to specific genes has been mapped in human lung cancer cells, a total of 16216 cisplatin-damaged genes (CDGs) with fold-enrichment > 1.5. Surprisingly, bioinformatics analysis demonstrates that cisplatin targets the majority of human protein kinase and phosphatase genes and involved in 300 core signalling pathways (-log p >4). The most associated key signalling pathways are sperm motility and protein kinase A. The highest related disease is cancer, and tissue toxicities related to CDGs are about hepato- and nephro- toxicities. Notably, cisplatin damaged 85% (440) of human protein kinase genes and 81% (110) of human protein phosphatase genes. This suggests that cisplatin acts as a multi-targeting protein-phosphorylation regulator, confirmed by a significant decrease in expression of a series of key protein kinase genes. These results reveal that cisplatin disrupts protein phosphorylation signalling genome-wide. Key points summarising the key messages of your articleA total of 16216 genes damaged by the clinical drug cisplatin in human lung cancer cells were identified using a forward chemical genetics method. Bioinformatics analysis revealed that cisplatin targets 85% of protein kinase and 81% of phosphatase genes. Cisplatin acts as a multi-targeting protein-phosphorylation regulator, disrupting protein phosphorylation signalling genome-wide. The disturbance of protein phosphorylation by cisplatin can be related to anticancer activity and tissue toxicities of the drug. These findings suggests novel strategies for rational design of next-generation anticancer metallodrugs involving specific targeting of protein phosphorylation.

cancer biology↗

Micropatterned Organoids Enable Modeling of the Earliest Stages of Human Cardiac Vascularization

Although model organisms have provided insight into the earliest stages of cardiac vascularization, we know very little about this process in humans. Here we show that spatially micropatterned human pluripotent stem cells (hPSCs) enable in vitro modeling of this process, corresponding to the first three weeks of in vivo human development. Using four hPSC fluorescent reporter lines, we create cardiac vascular organoids (cVOs) by identifying conditions that simultaneously give rise to spatially organized and branched vascular networks within endocardial, myocardial, and epicardial cells. Using single-cell transcriptomics, we show that the cellular composition of cVOs resembles that of a 6.5 post-conception week (PCW) human heart. We find that NOTCH and BMP pathways are upregulated in cVOs, and their inhibition disrupts vascularization. Finally, using the same vascular-inducing factors to create cVOs, we produce hepatic vascular organoids (hVOs). This suggests there is a conserved developmental program for creating vasculature within different organ systems. Graphic Abstract O_FIG O_LINKSMALLFIG WIDTH=159 HEIGHT=200 SRC="FIGDIR/small/499233v1_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@17b265org.highwire.dtl.DTLVardef@1c1113eorg.highwire.dtl.DTLVardef@531c18org.highwire.dtl.DTLVardef@596bd2_HPS_FORMAT_FIGEXP M_FIG C_FIG

developmental biology↗

CaSee: A lightning transfer-learning model directly used to discriminate cancer/normal cells from scRNA-seq

Single-cell RNA sequencing (scRNA-seq) is one of the most efficient technologies for human tumor research. However, data analysis is still faced with some technical challenges, especially the difficulty in efficiently and accurately discriminate cancer/normal cells in the scRNA-seq expression matrix. In this study, we developed a cancer/normal cell discrimination pipeline called pan-cancer seeker (CaSee) devoted to scRNA-seq expression matrix, which is based on the traditional high-quality pan-cancer bulk sequencing data using transfer learning. It is compatible with mainstream sequencings technology platforms, 10x Genomics Chromium, Smart-seq2, and Microwell-seq. Here, CaSee pipeline exhibited excellent performance in the multicenter data evaluation of 11 retrospective cohorts and one independent dataset, with an average discrimination accuracy of 96.69%. In general, the development of a deep-learning based, pan-cancer cell discrimination model, CaSee, to distinguish cancer cells from normal cells will be compelling to researchers working in the genomics, cancer, and single-cell fields.

bioinformatics↗

Structures of the Omicron Spike trimer with ACE2 and an anti-Omicron antibody

The Omicron variant of SARS-CoV-2 has rapidly become the dominant infective strain and the focus efforts against the ongoing COVID-19 pandemic. Here we report an extensive set of structures of the Omicron spike trimer by its own or in complex with ACE2 and an anti-Omicron antibody. These structures reveal that most Omicron mutations are located on the surface of the spike protein, which confer stronger ACE2 binding by nearly 10 folds but become inactive epitopes resistant to many therapeutic antibodies. Importantly, both RBD and the closed conformation of the Omicron spike trimer are thermodynamically unstable, with the melting temperature of the Omicron RBD decreased by as much as 7{degrees}C, making the spiker trimer prone to random open conformations. An unusual RBD-RBD interaction in the ACE2-spike complex unique to Omicron is observed to support the open conformation and ACE2 binding, serving the basis for the higher infectivity of Omicron. A broad-spectrum therapeutic antibody JMB2002, which has completed Phase 1 clinical trial, is found to interact with the same two RBDs to inhibit ACE2 binding, in a mode that is distinguished from all previous antibodies, thus providing the structural basis for the potent inhibition of Omicron by this antibody. Together with biochemical data, our structures provide crucial insights into higher infectivity, antibody evasion and inhibition of Omicron.

biophysics↗

A human antibody with blocking activity to RBD proteins of multiple SARS-CoV-2 variants including B.1.351 showed potent prophylactic and therapeutic efficacy against SARS-CoV-2 in rhesus macaques

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which causes coronavirus disease-2019 (COVID-19), interacts with the host cell receptor angiotensin-converting enzyme 2 (hACE2) via its spike 1 protein for infection. After the virus sequence was published, we identified two potent antibodies against SARS-CoV-2 RBD from antibody libraries using a phage-to-yeast (PtY) display platform in only 10 days. Our lead antibody JMB2002, now in a phase I clinical trial, showed broad-spectrum in vitro blocking activity against hACE2 binding to the RBD of multiple SARS-CoV-2 variants including B.1.351 that was reportedly much more resistant to neutralization by convalescent plasma, vaccine sera and some clinical stage neutralizing antibodies. Furthermore, JMB2002 has demonstrated complete prophylactic and potent therapeutic efficacy in a rhesus macaque disease model. Prophylactic and therapeutic countermeasure intervention of SARS-CoV-2 using JMB2002 would likely slow down the transmission of currently emerged SARS-CoV-2 variants and result in more efficient control of the COVID-19 pandemic.

microbiology↗

Genome-Wide Mapping of Cisplatin Damaged Gene Loci

Cisplatin is a DNA targeting anticancer drug, yet its damaged gene loci have remained unclear. In the present work, combining affinity isolation and high throughput sequencing, we genome-widely mapped 17729 gene loci containing platination lesions, which mainly function as enzymes, transcription regulators, transporters and kinases, and of which 445 genes account for 71% of potential gene targets for cancer therapy reported in the literature. The most related core signaling pathway, disease and tissue toxicity of 7578 genes with an enrichment fold (EFG) of >12, where EFG refers to the ratio of total read counts of a gene detected in cells with and without cisplatin treatment, are sperm motility, cancer and hepatotoxicity with association P values of < 1x10-22. Among 616 kinase genes damaged by cisplatin, 427 are protein kinases which account for 82% of putative protein kinases, suggesting that cisplatin may act as broad-spectrum protein kinase inhibitor. Western Blot assays verified that expression of 8 important protein kinase genes was significantly reduced due to cisplatin damage. SPAG9 is closely related to 147 of 361 cancer diseases which the cisplatin damaged genes are associated with and was severely damaged by cisplatin. Given SPAG9 abundantly expresses JIP-4, a upstream mediator of protein kinase signaling, in testis, it may be responsible for the high sensitivity of testicular cancer to cisplatin, thus being a potential therapeutic target for precise treatment of testicular cancer. These findings provide novel insights into better understanding in molecular mechanism of anticancer activity and toxicity of cisplatin, more importantly inspire further studies in prioritizing gene targets for precise treatment of cancers.

pharmacology and toxicology↗

Proteogenomics analysis of non-coding region encoded peptides in normal tissues and five cancer types

Previous proteogenomics studies have identified peptides encoded by non-coding sequences such as pseudogenes and long non-coding RNAs (lncRNAs) in healthy human tissues as well as in cancers. However, these studies are either limited to analyze only healthy or cancerous tissues, lacking direct comparison between them. In this study, we used an established proteogenomics analysis workflow to analyze proteomics data from 926 cancer samples of five cancer types and 31 different healthy human tissues. We observed the protein level expression of pseudogenes can be classified as ubiquitous or lineage expression. The ubiquitously translated pseudogenes are homologous to house-keeping genes. Our results suggest there is common mechanism underlying the translation of pseudogenes in both normal and tumors. Moreover, we discovered several translated non-coding genes such as DGCR5 and RHOXF1P3 that were up-regulated in tumors compared to normal. These translated pseudogenes imply the biological function of pseudogenes extends to protein level yet to be studied. Further, from the non-coding region encoded peptides specifically detected in tumors we have predicted a large number of potential neoantigens which can be developed as cancer vaccine.

bioinformatics↗

Human Chrysomya bezziana myiasis: A systematic review

BackgroundMyiasis due to Old World screw-worm fly, Chrysomya bezziana, is an important obligate zoonotic disease in the OIE-list of diseases and is found throughout much of Africa, the Indian subcontinent, southeast and east Asia. C. bezziana myiases cause not only morbidity and death to animals and humans, but also economic losses in the livestock industries. Because of the aggressive and destructive nature of this disease in hosts, we initiated this study to provide a comprehensive understanding of human myiasis caused by C. bezziana.\n\nMethodsWe conducted a systematic search of the databases in English (PubMed, Embase and African Index Medicus) and Chinese (CNKI, Wanfang, and Duxiu), and international government online reports to 6th February, 2019, to identify studies concerning Chrysomya bezziana. Another ten human cases in China and Papua New Guinea that our team had recorded were also included.\n\nResultsWe retrieved 1,048 reports from which 202 studies were ultimately eligible for inclusion in the present descriptive analyses. Since the first human case due to C. bezziana was reported in 1909, we have summarized 291 cases and found that these cases often occurred in poor hygiene, low socio-economic conditions, old age, and underlying diseases including infections, age-related diseases, and noninfectious chronic diseases. But C. bezziana myiasis appears largely neglected as a serious medical or veterinary condition, with human and animal cases only reported in 16 and 24 countries respectively, despite this fly species recorded as present in 44 countries worldwide.\n\nConclusionOur findings indicate that cryptic myiasis cases due to the obligate parasite, C. bezziana, are under-recognized. Through this in-depth study to clarify the knowledge of human C. bezziana myiasis including its etiology, clinical features, diagnosis, treatment, epidemiology, prevention and control, we call for more vigilance and awareness of the disease from governments, health authorities, clinicians, veterinary workers, nursing homes, and also the general public.\n\nAuthor summaryChrysomya bezziana larvae are characterized by feeding aggressively on the living tissues and body fluids of the host. The nightmare-like feelings of patients suffering from this myiasis, severe tissues and bones destruction, even death, and enormous economic loss in the livestock industries have been described in the previous reports. But our findings indicate that C. bezziana myiases still appear to be under-recognized as a serious medical or veterinary condition throughout the world. Both in China and the world at large, it is probable that C. bezziana distribution could be greater than currently reported. For the first time, we have therefore systematically investigated human myiasis caused by C. bezziana. Our study provides an opportunity for clinicians and health authorities to gain a better understanding of this disease from its etiology, pathology, clinical features, diagnosis, treatment, epidemiology, prevention and control. In addition, our findings will hopefully engage governments, health staff, veterinary workers, the elderly homes, and also the general public in efforts to recognize, prevent and control such infestations.

epidemiology↗

Scalable volumetric imaging for ultrahigh-speed brain mapping at synaptic resolution

We describe a new light-sheet microscopy method for fast, large-scale volumetric imaging. Combining synchronized scanning illumination and oblique imaging over cleared, thick tissue sections in smooth motion, our approach achieves high-speed 3D image acquisition of an entire mouse brain within 2 hours, at a resolution capable of resolving synaptic spines. It is compatible with immunofluorescence labeling, enabling flexible cell-type specific brain mapping, and is readily scalable for large biological samples such as primate brain.

neuroscience↗