Biology subjects

Pang, C.

Publications and source records attributed to Pang, C..

11 recordsLinked to original sources

bioRxiv2026

Charting sex divergence in the human brain across the lifespan

Biological sex fundamentally shapes human brain organization, but sex-specific normative neuroanatomical trajectories across the lifespan remain largely uncharted. Here, we constructed independent, sex-specific lifespan brain charts using structural neuroimaging data from 59,915 healthy individuals (29,760 males and 30,155 females) ranging in age from 266 postconception days to 100 years. By examining 296 structural phenotypes across global, cortical, and subcortical measures, these models revealed widespread sex differences in maturational timing, with males reaching peak milestones later than females. These trajectories demonstrate that sex differences evolve dynamically, with phenotype-specific windows of emergence and maximal separation. Compared with conventional sex-pooled references, sex-specific models achieved superior predictive accuracy and reduced misestimation of individual deviations in healthy populations. Across five neuropsychiatric conditions, sex-specific models improved the detection of extreme deviations and revealed both shared and sex-dependent patterns of disorder-related neuroanatomical abnormalities. These sex-specific charts establish tailored normative references for assessing brain development, ageing, and disease.

neuroscience↗

bioRxiv2026

Pervasive historical introgression across oak phylogeny shapes gene expression

Oaks were once described as the "worst-case scenario" for the biological species concept because of the presumed pervasive hybridization and introgression among species. However, we still lack a full picture of genome-wide introgression across the eight sections of the Quercus phylogeny. Furthermore, we still do not have a complete characterization of what is introgressed and how it functionally influences the recipient species. Firstly, we used 168 whole genomes from 67 Quercus species belonging to the eight sections of the Quercus phylogeny and a super pan-genome to generate a phylogeny and test for ILS and introgression. Introgression was widespread: ancient introgression occurred between ancestors of the eight sections and more recent introgression took place within sections. Secondly, using genome-wide transcriptome, methylome, and chromatin accessibility data from a subset of 19 species sampled from four sections we demonstrated that introgressed genes are more highly and uniformly expressed than non-introgressed ones. This difference in expression level between introgressed and non-introgressed genes mostly results from cis-regulation, and is most likely due to DNA methylation decay in promoter ACRs. In summary, introgression has been a major evolutionary force during the whole evolutionary history of Quercus and had a significant impact on fundamental processes such as gene regulation and expression.

evolutionary biology↗

bioRxiv2026

Tunable Rigid Spikes on Virus-Like Porous Silica Enable Mechanistically Controlled Nanovaccine Platforms

Virus-like particles represent an emerging and promising vaccine platform. However, these particles are inherently mechanically soft and have limited control over particle surface architecture, thereby constraining their immunological control. Herein, we report the rational design of bioinspired virus-like porous silica (VLPSi) nanoparticles (NPs) with tunable and mechanically rigid spike architectures that function dually as antigen delivery carriers and immune adjuvants. Using ovalbumin (OVA) as a model antigen, we systematically elucidate the spiky structure-function relationship in antigen delivery and immune response. VLPSi NPs exhibit good biocompatibility, sustained antigen release, and markedly enhanced cellular uptake and endosomal escape compared with soft spike and spherical counterparts. Mechanistic investigations combining molecular dynamics simulations and proteomic analyses reveal that rigid spike architectures reduce the energetic barrier for cellular internalization and concurrently activate dual pathways involving endosomal Toll like receptors and calcium signaling. Consequently, VLPSi with long spikes elicit significantly enhanced humoral and cellular immune responses, outperforming the particles with shorter spikes, spherical shape as well as clinically used alum adjuvant. To demonstrate translational potential, bioinspired antibacterial vaccines were produced by loading Staphylococcus aureus surface protein rEsxB. The VLPSi-based vaccine elicited robust protective immunity to achieve complete (100%) survival following lethal challenge without detectable adverse effects, whereas traditional Alum-adjuvanted formulation conferred only minimal protection, with a survival rate of 10%. Collectively, this work establishes VLPSi with tunable spikes as a mechanistically controlled platform for next generation vaccines. Graphic Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=145 SRC="FIGDIR/small/720861v1_ufig1.gif" ALT="Figure 1"> View larger version (47K): org.highwire.dtl.DTLVardef@1f6c13eorg.highwire.dtl.DTLVardef@1090d07org.highwire.dtl.DTLVardef@1364926org.highwire.dtl.DTLVardef@fc68ab_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2025

Effects of oral cannabidiol (CBD) on spontaneous opioid withdrawal in male and female rats

Opioid use disorder (OUD) remains a public health crisis in the United States. A key factor in continued use, relapse risk, and overdose is the severe withdrawal syndrome that accompanies abstinence. Observational studies suggest cannabis may improve outcomes for patients with OUD. Cannabidiol (CBD), a non-intoxicating compound found in cannabis, is being investigated as a potential treatment for OUD. This study investigated whether CBD alleviated withdrawal symptoms in a rat model of opioid dependence. Sprague Dawley rats (N = 100, 50% female) were administered escalating doses of morphine across 10 days (10-50 mg/kg, s.c., twice daily). Following abrupt discontinuation, withdrawal outcomes were evaluated across acute (38-hr) and protracted (up to day 7) timepoints. Rats were treated with pure CBD (10 or 30 mg/kg, p.o.) or vehicle (sesame oil; 1 mg/ml) daily, beginning 14-hrs after their final morphine or saline injection (n = 8-9 per sex/group). Withdrawal severity was assessed through physical measurements of body weight, food intake, and somatic signs (e.g., body shakes, diarrhea), and pain sensitivity, as well as measurements of anxiety-like behaviors in the protracted phase. Compared to non-dependent controls, morphine-dependent rats had decreased body weight and food intake, showed greater somatic signs, and had increased pain sensitivity that peaked in acute withdrawal (38-hr). Oral CBD did not affect physical symptoms of opioid withdrawal nor protracted anxiety-like behaviors. These data indicate that CBD alone may have limited effectiveness for treating opioid withdrawal. Reports of improved withdrawal symptoms after cannabis use may be attributed to other compounds in cannabis. Public health significanceThis study suggests that daily oral treatment with pure CBD at doses available to consumers does not improve physical or psychological symptoms of withdrawal from chronic opioids.

pharmacology and toxicology↗

bioRxiv2025

Cryo-electron microscopy structures of a high-affinity zinc ABC transporter

Zn2+ is an essential micronutrient to all living organisms and plays a key role in various physiological functions. Microorganisms employ high-affinity Zn2+ ABC transporters to uptake zinc from the environment when it is scarce. However, the mechanism of zinc uptake and its regulation remain poorly understood. Here, we report the cryo-electron microscopy structure of the Zn2+ ABC transporter complex ZnuB-ZnuC from Escherichia Coli. The complex has two ZnuB subunits for transport and two ZnuC subunits for regulation. The ZnuB homodimer is in an outward-facing, closed conformation with a large hydrophilic cavity at the dimer interface. The ZnuC subunits contain an N-terminal ATP-binding cassette (ABC) domain (NBD) and a C-terminal zinc-sensing domain (ZSD). Zn2+ binding to the ZSD locks the transporter in a closed state regardless of nucleotide, whereas under low-Zn2+ conditions, ZSD C-terminal disorder permits ATP-driven zinc uptake. High-affinity zinc ABC transporters are ubiquitously utilized by pathogenic bacteria to evade host immune systems in competing for essential Zn2+. These findings highlight new pharmaceutical targets for disrupting Zn2+ homeostasis in antibiotic-resistant pathogens. One-sentence summaryHigh-affinity zinc ABC transporter structures show a self-regulating mechanism via a built-in zinc sensor.

biochemistry↗

bioRxiv2024

P450-Catalyzed Biaryl Macrocyclization of Leaderless Ribosomal Peptides

Macrocyclic peptides containing biaryl motifs, predominantly derived from natural products, are valuable scaffolds due to their structural rigidity and potent bioactivity. However, current synthetic methods remain constrained by the absence of broadly applicable strategies across chemocatalytic and biocatalytic platforms. Here, we discover a versatile P450 enzyme, GpeC, capable of facilitating oxidative C-C/O/N cross-coupling for peptide biaryl macrocyclization (PBC) with leader-independent activity. Crystal structure analysis of GpeC rationalizes leader-independent property and reveals adaptive recognition that enables access to diverse biaryl-linked macrocycles. GpeC exhibits exceptional substrate promiscuity, accommodating 19 of 20 canonical amino acids and diverse noncanonical analogs within a minimal tetrapeptide scaffold. The efficient semi-synthesis of the natural product Rubrin further demonstrated the versatility of GpeC. We further introduced lytic to tetraregion (LTT), a one-step, single enzyme synthesis for modular synthesis of biaryl-cyclized tetrapeptide. Overall, GpeCs robustness and programmability position it as a broadly applicable biocatalyst for the synthesis of biaryl macrocyclic peptides.

biochemistry↗

bioRxiv2023

Functional connectome through the human life span

The lifespan growth of the functional connectome remains unknown. Here, we assemble task-free functional and structural magnetic resonance imaging data from 33,250 individuals aged 32 postmenstrual weeks to 80 years from 132 global sites. We report critical inflection points in the nonlinear growth curves of the global mean and variance of the connectome, peaking in the late fourth and late third decades of life, respectively. After constructing a fine-grained, lifespan-wide suite of system-level brain atlases, we show distinct maturation timelines for functional segregation within different systems. Lifespan growth of regional connectivity is organized along a primary-to-association cortical axis. These connectome-based normative models reveal substantial individual heterogeneities in functional brain networks in patients with autism spectrum disorder, major depressive disorder, and Alzheimers disease. These findings elucidate the lifespan evolution of the functional connectome and can serve as a normative reference for quantifying individual variation in development, aging, and neuropsychiatric disorders.

neuroscience↗

bioRxiv2022

Semaphorin3F reduces vascular endothelial and smooth muscle cell PI3K activation and decreases neointimal plaque formation

We previously conducted genetic analyses, and identified semaphorin signaling as associating with coronary artery disease. Of the semaphorins, human vascular expression profiling suggested SEMA3F as potentially linked to atherogenesis. In hyperlipidemic mice, SEMA3F reduced aortic lesion area, and increased fibrous cap endothelial content, leading to plaque stability. In a disturbed-flow-mediated endothelial dysfunction-driven lesion model, the absence of Sema3f increased plaques, further implicating SEMA3F in endothelial function. Monocyte adhesion to Sema3f-/- vascular endothelial cells (VECs) was elevated, driven by increased PI3K activity, leading to increased NF-{kappa}B-mediated elevation in VCAM1 and ICAM1 expression, suggesting that SEMA3F reduces VEC PI3K activity. Increased permeability led to increased monocyte transmigration through Sema3f-/- VECs, and mTOR phosphorylation was decreased, suppressing VE-cadherin expression and cell-cell adherens junction stability. Actomyosin fiber formation was decreased in Sema3f-/- VECs, which was reversed by PI3K inhibition, further implicating SEMA3F in adherens junction stability. In Sema3f-/- vascular smooth muscle cells (VSMCs), active PI3K was also increased. PI3K facilitates VSMC proliferation, migration, and pro-atherogenic phenotype switching, which were reduced by SEMA3F. In agreement, in a model of VSMC proliferation and migration-induced neointima formation, SEMA3F reduced plaques. Semaphorin3F is causally atheroprotective. SEMA3Fs suppression of VEC and VSMC PI3K activation may contribute to its atheroprotection.

physiology↗

bioRxiv2021

Accurate Name Entity Recognition for Biomedical Literatures: A Combined High-quality Manual Annotation and Deep-learning Natural Language Processing Study

A combined high-quality manual annotation and deep-learning natural language processing study is reported to make accurate name entity recognition (NER) for biomedical literatures. A home-made version of entity annotation guidelines on biomedical literatures was constructed. Our manual annotations have an overall over 92% consistency for all the four entity types -- gene, variant, disease and species --with the same publicly available annotated corpora from other experts previously. A total of 400 full biomedical articles from PubMed are annotated based on our home-made entity annotation guidelines. Both a BERT-based large model and a DistilBERT-based simplified model were constructed, trained and optimized for offline and online inference, respectively. The F1-scores of NER of gene, variant, disease and species for the BERT-based model are 97.28%, 93.52%, 92.54% and 95.76%, respectively, while those for the DistilBERT-based model are 95.14%, 86.26%, 91.37% and 89.92%, respectively. The F1 scores of the DistilBERT-based NER model retains 97.8%, 92.2%, 98.7% and 93.9% of those of BERT-based NER for gene, variant, disease and species, respectively. Moreover, the performance for both our BERT-based NER model and DistilBERT-based NER model outperforms that of the state-of-art model--BioBERT, indicating the significance to train an NER model on biomedical-domain literatures jointly with high-quality annotated datasets.

bioinformatics↗

bioRxiv2021

AlphaFold Protein Structure Database for Sequence-Independent Molecular Replacement

Crystallographic phasing recovers the phase information that is lost during a diffraction experiment. Molecular replacement is a dominant phasing method for the crystal structures in the protein data bank. In one form it uses a protein sequence to search a structure database for finding suitable templates for phasing. However, such sequence information is not always available such as when proteins are crystallized with unknown binding partner proteins or when the crystal is that of a contaminant. The recent development of AlphaFold has resulted in the availability of predicted protein structures for all proteins from twenty species. In this work, we tested whether AlphaFold-predicted E. coli protein structures were accurate enough for sequence-independent phasing of diffraction data from two crystallization contaminants for which we had not identified the protein. Using each of more than 4000 predicted structures as a search model, robust molecular replacement solutions were obtained which allowed the identification and structure determination of both structures, YncE and YadF. Our results advocate a general utility of AlphaFold-predicted structure database with respect to crystallographic phasing.

biochemistry↗

bioRxiv2021

Structural Basis for SARS-CoV-2 Envelope Protein in Recognition of Human Cell Junction Protein PALS1

The COVID-19 pandemic caused by the SARS-CoV-2 virus has created a global health and economic emergency. SARS-CoV-2 viruses hijack human proteins to promote their spread and virulence including the interactions involving the viral envelope (E) protein and human proteins. To understand the structural basis for SARS-CoV-2 viral-host recognition, we used cryo-electron microscopy to determine a structure for the human cell junction protein PALS1 and SARS-CoV-2 E protein complex. The structure shows that the E protein C-terminal DLLV motif recognizes a pocket formed exclusively by hydrophobic residues from the PDZ and SH3 domains in PALS1. Our structural analysis provides an explanation for the observation that the viral E protein recruits PALS1 from lung epithelial cell junctions resulting in vascular leakage, lung damage, viral spread, and virulence. In addition, our structure provides novel targets for peptide- and small-molecule inhibitors that could block the PALS1-E interactions to reduce the E-mediated damage to vascular structures.

biochemistry↗