Biology subjects

Xiang, Z.

Publications and source records attributed to Xiang, Z..

At least 19 recordsLinked to original sources

bioRxiv2026

Generation and application of human pluripotent stem cells derived peri-nervoids

Autologous nerve grafts remain the gold standard for peripheral nerve repair, but donor scarcity, donor-site morbidity and incomplete functional recovery limit their use. Schwann cells (SCs) drive autograft-mediated regeneration, yet their limited availability and expansion impede SC-based therapies. Here, we generated human pluripotent stem cell-derived SCs, motor neuron-enriched spinal cord organoids and nociceptive sensory neuron-enriched dorsal root ganglion organoids, and assembled them into a nerve-like construct termed the Peri-nervoid. Single-cell RNA sequencing revealed context-dependent SC plasticity: axonal co-culture promoted myelination, whereas axonal transection induced a repair phenotype resembling SC dedifferentiation during Wallerian degeneration. Following transplantation into 7-mm sciatic nerve defects in NSG mice, human SCs survived and remyelinated regenerating host axons, while axon-containing grafts enhanced regeneration relative to SC-only grafts. No abnormal proliferation, systemic toxicity or major-organ histopathology was detected. These findings position the Peri-nervoid as a scalable, developmentally inspired platform for developing engineered grafts for peripheral nerve repair.

bioengineering↗

bioRxiv2025

Scalable flow synthesis of ultrasmall inorganic nanoparticles for biomedical applications via a confined impinging jet mixer

Ultrasmall inorganic nanoparticles (sub-5 nm) have unique biomedical advantages due to rapid clearance, enhanced imaging contrast, and potent therapeutic properties. However, current synthesis methods are limited by low throughput, polydispersity, and reliance on harsh conditions such as organic solvents or high temperatures. We report a scalable, single-step aqueous synthesis using a confined impinging jet mixer (CIJM) that produces size-controlled, clinically relevant nanoparticles, including silver sulfide, silver telluride, cerium oxide, and iron oxide, under ambient conditions. The resulting nanoparticles are homogeneous, stable, and preserve their functional biological properties. We demonstrate consistent performance across scales, establishing the CIJM as a versatile and reproducible method for producing ultrasmall inorganic nanoparticles suitable for clinical translation and high-throughput biomedical applications.

bioengineering↗

bioRxiv2025

VO: The Vaccine Ontology

With the widespread use of vaccines in research and clinical settings, there is an urgent need to standardize vaccine representation, integrate information across diverse vaccine types, and support computer-assisted reasoning. Accordingly, we have since 2007 developed the community-based Vaccine Ontology (VO), which aligns with the Basic Formal Ontology and adheres to OBO Foundry principles. VO models ontologically vaccines, vaccine components, vaccine immune responses, vaccine investigation studies and other vaccine-related topics. VO represents more than 10,000 vaccines targeting 289 infectious pathogens and cancers in humans and over 30 nonhuman animal species. VO provides mappings to external resources such as RxNorm, CVX, FDA, and USDA. Various VO use cases exist. VO facilitates vaccine standardization in resources such as the VIOLIN vaccine database, ImmPort, and the Vaccine Adjuvant Compendium (VAC). Semantic queries can be made to query VO. VO has been shown to enhance experimental and clinical vaccine data analysis and vaccine literature mining. Overall, VO standardizes vaccine modeling and representation and greatly supports vaccine AI research in the Semantic Web era.

bioinformatics↗

bioRxiv2025

Geometric Evaluation and Optimization of Maize Leaf Morphology and Canopy Architecture

Maize leaf and canopy are the primary media to interact with environmental factors, including light interception, water evaporation, wind fluctuation, etc. Leaf morphology and canopy architecture affect the interaction process and activity significantly. Maize canopy architecture, a critical determinant of light capture and photosynthetic efficiency, is influenced by complex interactions between leaf morphology and arrangement. This study aimed to explore the relationships between key leaf morphological traits (midrib shape, blade contour, undulations) and canopy architecture in maize, and to identify optimal leaf morphologies for light interception. We employed correlation analysis and stepwise Bayesian optimization to quantify the relationships between leaf traits and to identify optimal leaf morphologies for maximizing leaf area and minimizing self-shading. Our results revealed that midrib shape and leaf width distribution positively influence leaf area, while undulation has a bidirectional effect depending on its orientation. Optimization results showed that optimal canopies feature upright top leaves, intermediately erect middle leaves, and relatively flat bottom leaves. This study provides a quantitative framework for understanding and predicting optimal canopy structure in maize, which can inform breeding strategies aimed at improving light utilization and yield potential.

systems biology↗

bioRxiv2024

Association study of Plasmodium falciparum Acetyl-CoA Synthetase Mutations S868G and V949I with antimalarial drugs

Plasmodium falciparum acetyl-CoA synthetase (PfACAS) protein is an important source of acetyl-CoA. We detected the mutations S868G and V949I in PfACAS by whole-genome sequencing analysis in some recrudescent parasites after antimalarial treatment with artesunate and dihydroartemisinin-piperaquine, suggesting that they may confer drug resistance. Using CRISPR/Cas9 technology, we engineered parasite lines carrying the PfACAS S868G and V949I mutations in two genetic backgrounds and evaluated their susceptibility to antimalarial drugs in vitro. The results demonstrated that PfACAS S868G and V949I mutations alone or in combination were not enough to provide resistance to antimalarial drugs.

microbiology↗

bioRxiv2024

A unique mechanism of snRNP core assembly

The assembly of spliceosomal snRNP cores involves seven Sm proteins (D1/D2/F/E/G/D3/B) forming a ring around each snRNA and typically requires several essential assembly chaperones, particularly the SMN-Gemins complex implicated in spinal muscular atrophy (SMA). Strikingly, in budding yeast, snRNP core assembly only involves Brr1, a nonessential homolog of Gemin2. To unravel this enigma, we systematically investigated snRNP core assembly in budding yeast using biochemical and genetic approaches. We discovered two distinct pathways in budding yeast: chaperone-mediated and direct. The chaperone-mediated pathway involves two proteins, Brr1 and a novel protein, Lot5, but is inefficient. Lot5 binds D1/D2/F/E/G to form a heterohexameric ring (6S). Brr1 binds D1/D2/F/E/G and 6S but cannot displace Lot5 to facilitate assembly. Disruption of both BRR1 and LOT5 genes caused mild growth retardation, but LOT5 overexpression substantially impeded growth. The direct pathway uniquely involves F/E/G as a trimer and a stable D1/D2/F/E/G intermediate complex, explaining the non-essentiality of assembly chaperones. These findings unveil a unique assembly mechanism of snRNP cores, illuminate the evolution of assembly chaperones, and suggest avenues for studying SMA pathophysiology.

molecular biology↗

bioRxiv2024

Acetyl-CoA Synthetase Mutations S868G and V949I Do Not Confer Resistance to Antimalarial Drugs in vitro in Plasmodium falciparum.

microbiology↗

bioRxiv2024

Inference of chromosome selection parameters and missegregation rate in cancer from DNA-sequencing data

Aneuploidy is frequently observed in cancers and has been linked to poor patient outcome. Analysis of aneuploidy in DNA-sequencing (DNA-seq) data necessitates untangling the effects of the Copy Number Aberration (CNA) occurrence rates and the selection coefficients that act upon the resulting karyotypes. We introduce a parameter inference algorithm that takes advantage of both bulk and single-cell DNA-seq cohorts. The method is based on Approximate Bayesian Computation (ABC) and utilizes CINner, our recently introduced simulation algorithm of chromosomal instability in cancer. We examine three groups of statistics to summarize the data in the ABC routine: (A) Copy Number-based measures, (B) phylogeny tip statistics, and (C) phylogeny balance indices. Using these statistics, our method can recover both the CNA probabilities and selection parameters from ground truth data, and performs well even for data cohorts of relatively small sizes. We find that only statistics in groups A and C are well-suited for identifying CNA probabilities, and only group A carries the signals for estimating selection parameters. Moreover, the low number of CNA events at large scale compared to cell counts in single-cell samples means that statistics in group B cannot be estimated accurately using phylogeny reconstruction algorithms at the chromosome level. As data from both bulk and single-cell DNA-sequencing techniques becomes increasingly available, our inference framework promises to facilitate the analysis of distinct cancer types, differentiation between selection and neutral drift, and prediction of cancer clonal dynamics.

evolutionary biology↗

bioRxiv2024

Genomic insights into photosymbiotic evolution in Tridacna squamosa

Photosymbiosis is fundamental driving force for ecological success of benthic coral reef ecosystems, and contributing to their biodiversity and resilience. As a benchmark organism indicative of reef health, the fluted giant clam (Tridacna squamosa) forms an exemplary photosymbiotic relationship with the symbiont Symbiodiniaceae dinoflagellates, whose initiation and maturation require finely coordinated interactions. However, much of the origin and dynamics of this reciprocal interplay remains unclarified. Here, we report the first complete whole genome of T. squamosa, in conjunction with integrated multi-omics data, to illuminate the key evolutionary innovations and molecular events supporting the establishment and maintenance of photosymbiotic lifestyle in the giant clam. Programmed regulation of symbiont recognition, host immune system and GPCRs signaling activation co-contributed to dinoflagellates acquisition in T. squamosa larvae. Adaptive metabolic remodeling in the host siphonal mantle, a photosymbiotic niche, is critical to maintain the robustness of phtosymbiosis. T. squamosa has expanded light sensing gene family and evolved sophisticated signaling pathways to protect against UV photo-damage. Evidence also supports significant contribution of positive selection to host DNA-repair. Overall, our study here offers fresh mechanistic insights into the parallel evolution and molecular machinery of photosymbiosis in the giant clam-dinoflagellates duet, with implications for devising solutions to sustainable conservation.

evolutionary biology↗

bioRxiv2023

Exploring information exchange between Thesium chinense and its host Prunella vulgaris through joint transcriptomic and metabolomic analysis

Background: Thesium chinense known as "plant antibiotic" is a facultative root hemi-parasitic herb while Prunella vulgaris can serve as its host. However, the molecular mechanisms underlying the communication between T. chinense and its host remained largely unexplored. The aim of this study was to provide a comprehensive view of transferred metabolites and mobile mRNAs between T. chinense and P. vulgaris. Results: The wide-target metabolomic and transcriptomic analysis identified 5 transferred metabolites and 668 mobile genes between T. chinense and P. vulgaris, as well as haustoria formation related 56 metabolites and 189 genes. Furthermore, we inferred a regulatory network that might be involved in haustoria formation, and 18 genes promoting haustoria formation and 1 gene inhibiting it were identified as a consequence. There were 4 metabolites (ethylsalicylate, eriodictyol-7-O-glucoside, aromadendrin-7-O-glucoside and pruvuloside B) that are transferred from P. vulgaris to T. chinense, whereas 2-ethylpyrazine was transferred from T. chinense to P. vulgaris. Conclusions: These results suggested that there was an extensive exchange of information with P. vulgaris including transferred metabolites and mobile mRNAs, which might facilitate the haustoria formation and parasition of T. chinense. Author summaryT. chinense known as "plant antibiotic" is a facultative root hemi-parasitic herb while P. vulgaris can serve as its host. Currently, the information exchange between T. chinense and its host remained unknown, and a comprehensive view of transferred metabolites and mobile mRNAs between T. chinense and its host is critical so that appropriate chemical and genetic improvement can be used to facilitate haustoria formation and successful parasitism. Here, we employ the conjoint wide-target metabolomic and transcriptomic analysis to explore the information exchange between T. chinense and P. vulgaris. We identified 5 transferred metabolites and 668 mobile genes between T. chinense and P. vulgaris, as well as haustoria formation related 56 metabolites and 189 genes. Our study provides new insights into the complex interplay between parasite and host during parasitism.

plant biology↗

bioRxiv2023

Millimeter-scale magnetic implants paired with a fully integrated wearable device for wireless biophysical and biochemical sensing

Implantable sensors can directly interface with various organs for precise evaluation of health status. However, extracting signals from such sensors must rely on transcutaneous wires, integrated circuit chips, or cumbersome readout equipment, which increases the risks of infection, reduces the biocompatibility, or limits the portability. Here, we develop a set of millimeter-scale, chip-less and battery-less magnetic implants that can measure biophysical and biochemical signals wirelessly. In particular, the implants form two-way communications with a fully integrated wearable device, where the wearable device can induce a large-amplitude damped vibration of the magnetic implants and capture their subsequent motions in a wireless manner. Such damped vibrations reflect not only the biophysical conditions surrounding the implants movements, but also the concentration of a specific biochemical depending on the surface modification. Experiments in rat models demonstrate the capabilities in measuring cerebrospinal fluid (CSF) viscosity, intracranial pressure (ICP), and CSF glucose levels. This miniaturized system opens possibility for continuous, wireless monitoring of a wide range of biophysical and biochemical conditions within the living organism.

bioengineering↗

bioRxiv2023

Synthetic Echocardiograms Generation Using Diffusion Models

An echocardiogram is a video sequence of a human heart captured using ultrasound imaging. It shows heart structure and motion and helps in diagnosis of cardiovascular diseases. Deep learning methods, which require large amounts of training data have shown success in using echocardiograms to detect cardiovascular disorders such as valvular heart disease. Large datasets of echocardiograms that can be used for machine learning training are scarce. One way to address this problem is to use modern machine learning generative methods to generate synthetic echocardiograms that can be used for machine learning training. In this paper, we propose a video diffusion method for the generation of echocardiograms. Our method uses a 3D selfattention mechanism and a super-resolution model. We demonstrate that our proposed method generates echocardiograms with higher resolution and with lesser artifacts, compared to existing echocardiogram generation methods.

bioengineering↗

bioRxiv2023

Enterocytozoon hepatopenaei Proliferate in Procambarus clarkii: A Warning for Crayfish and Shrimp Aquaculture

The pacific whiteleg shrimp (Litopenaeus vannamei) and the crayfish (Procambarus clarkii) are the most productive aquatic animals in the world. The prevalence of the microsporidium Enterocytozoon hepatopenaei (EHP), an intracellular spore-forming unicellular parasite which leading retarded growth of L. vannamei, has caused severe economic losses in most shrimp farming country. In this study, we found that the wild P. clarkii, living in shrimp ponds with EHP outbreak, excreted white faeces after temporary laboratory culture. The hepatopancreas (HP) of symptomatic crayfish exhibited a lighter color and severely atrophied. H&E-stain showed tissue lesions in both hepatopancreas and intestine, and clustered microsporidian spores were filled in the cytoplasm of the cells. PCR using EHPptp2 and two microsporidian-universal primers sets demonstrated the existence of EHP in the hepatopancreas, intestine and the white feces of P. clarkii. The EHP loads of 103-104 copies of EHPptp2/50 ng HPgDNA were detected by qPCR. Developing stages and mature spores of EHP were observed in hepatopancreas of P. clarkii through indirect-immunofluorescence assay (IFA) and transmission electron microscopy (TEM). Considering the large-scale cultivation of L. vannamei and P. clarkii, overlap farming areas between these two species as well as the ability of crayfish to crawl on land and water, our finding indicates the potential role of P. clarkii in the transmission of EHP, and it is an early warning for crayfish and shrimp farming.

microbiology↗

bioRxiv2023

A novel virus-induced cyclic dinucleotide, 2'3'-c-di-GMP, mediates STING-dependent antiviral immunity in Drosophila

In mammals, the enzyme cGAS senses the presence of cytosolic DNA and synthesizes the cyclic dinucleotide (CDN) 2'3'-cGAMP. This CDN binds to and activates the protein STING to trigger immunity. We recently discovered in the model organism Drosophila melanogaster two cGAS-like receptors (cGLRs) that activate STING-dependent antiviral immunity and can produce 3'2'-cGAMP, in addition to 2'3'-cGAMP. Here we explore CDN-mediated immunity in 14 different Drosophila species covering 50 million years of evolution and report that 2'3'-cGAMP and 3'2'-cGAMP fail to control infection by Drosophila C virus in D. serrata, D. sechellia and D. mojavensis. Using an accurate and sensitive mass spectrometry method, we discover an unexpected diversity of CDNs produced in a cGLR-dependent manner in response to viral infection in D. melanogaster, including a novel CDN, 2'3'-c-di-GMP. We show that 2'3'-c-di-GMP is the most potent STING agonist identified so far in D. melanogaster and that this molecule also activates a strong antiviral transcriptional response in D. serrata. Our results shed light on the evolution of cGLRs in flies and provide a basis for the understanding of the function and regulation of this emerging family of PRRs in animal innate immunity.

immunology↗

bioRxiv2022

Chromosome-level Genomes Reveal the Genetic Basis of Descending Dysploidy and Sex Determination in Morus Plants

Multiple plant lineages have independently evolved sex chromosomes and variable karyotypes to maintain their sessile lifestyles through constant biological innovation. Morus notabilis, a dioecious mulberry species, has the fewest chromosomes among Morus spp., but the genetic basis of sex determination and karyotype evolution in this species have not been identified. Three high-quality genome assemblies generated of Morus spp. (including those of dioecious M. notabilis and Morus yunnanensis) were within the range 301-329 Mb in size which were grouped into six pseudochromosomes. Using a combination of genomic approaches, we showed that the putative ancestral karyotype of Morus was close to 14 protochromosomes, and that several chromosome fusion events resulted in descending dysploidy (2n = 2x = 12). We also characterized a [~]6.2-Mb sex-determining region on chromosome 3. The four potential male-specific genes, including a partially duplicated DNA helicase gene orthologue (named MSDH) and three Ty3_Gypsy long terminal repeat retrotransposons (named MSTG), were solely identified in the Y-linked area and considered to be strong candidate genes for sex determination or differentiation. Population genomic analysis showed that Guangdong accessions in China were genetically similar to Japanese accessions of mulberry. In addition, genomic areas containing selective sweeps that distinguish domesticated mulberry trees from wild populations in terms of flowering and disease resistance were identified. Our findings provide an important genetic resource for sex identification and molecular breeding in mulberry.

genomics↗

bioRxiv2022

PPML-Omics: a Privacy-Preserving federated Machine Learning system protects patients' privacy from omic data

Modern machine learning models towards various tasks with omic data analysis give rise to threats of privacy leakage of patients involved in those datasets. Despite the advances in different privacy technologies, existing methods tend to introduce too much computational cost (e.g. cryptographic methods) or noise (e.g. differential privacy), which hampers either model usefulness or accuracy in protecting privacy in biological data. Here, we proposed a secure and privacy-preserving machine learning method (PPML-Omics) by designing a decentralized version of the differential private federated learning algorithm. We applied PPML-Omics to analyze data from three sequencing technologies, and addressed the privacy concern in three major tasks of omic data, namely cancer classification with bulk RNA-seq, clustering with single-cell RNA-seq, and the integration of spatial gene expression and tumour morphology with spatial transcriptomics, under three representative deep learning models. We also examined privacy breaches in depth through privacy attack experiments and demonstrated that PPML-Omics could protect patients privacy. In each of these applications, PPML-Omics was able to outperform methods of comparison under the same level of privacy guarantee, demonstrating the versatility of the method in simultaneously balancing the privacy-preserving capability and utility in practical omic data analysis. Furthermore, we gave the theoretical proof of the privacy-preserving capability of PPML-Omics, suggesting the first mathematically guaranteed method with robust and generalizable empirical performance in protecting patients privacy in omic data.

bioinformatics↗

bioRxiv2022

Prime-boost vaccinations with two serologically distinct chimpanzee adenovirus vectors expressing SARS-CoV-2 spike or nucleocapsid tested in a hamster COVID-19 model

Two serologically distinct replication-defective chimpanzee-origin adenovirus (Ad) vectors (AdC) called AdC6 and AdC7 expressing the spike (S) or nucleocapsid (N) proteins of an early SARS-CoV-2 isolate were tested individually or as a mixture in a hamster COVID-19 challenge model. The N protein, which was expressed as a fusion protein within herpes simplex virus glycoprotein D (gD) stimulated antibodies and CD8+ T cells. The S protein expressing AdC (AdC-S) vectors induced antibodies including those with neutralizing activity that in part cross-reacted with viral variants. Hamsters vaccinated with the AdC-S vectors were protected against serious disease and showed accelerated recovery upon SARS-CoV-2 challenge. Protection was enhanced if AdC-S vectors were given together with the AdC vaccines that expressed the gDN fusion protein (AdC-gDN). In contrast hamsters that just received the AdC-gDN vaccines showed only marginal lessening of symptoms compared to control animals. These results indicate that immune response to the N protein that is less variable that the S protein may potentiate and prolong protection achieved by the currently used genetic COVID-19 vaccines.

immunology↗

bioRxiv2022

Pre-clinical testing of two serologically distinct chimpanzee-origin adenovirus vectors expressing spike of SARS-CoV-2

Two serologically distinct chimpanzee-origin, replication-defective adenovirus (AdC) vectors expressing the spike (S) protein of an early severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) isolate were generated and tested for induction of antibodies in young and aged mice. Both vectors induced S protein-specific antibodies including neutralizing antibodies. Levels of antibodies increased after a boost. The effectiveness of the boost depended on vector dose and timing between the two immunizations. Using two heterologous AdC vectors was more effective than vaccinating with the same vector repeatedly. Antibodies partially crossreacted between different S protein variants. Cross-reactivity increased after booster immunization with vectors carrying the same S gene, expression of two different S proteins by the AdC vectors used for the prime and the boost did not selectively increase responses against the variants.

immunology↗