Biology subjects

Zhang, X.-J.

Publications and source records attributed to Zhang, X.-J..

8 recordsLinked to original sources

bioRxiv2025

Early-onset β-amyloidosis in human brains with hematological malignances and cardiovascular diseases: Revisiting injury/stress induced axonal pathology

{beta}-Amyloid (A{beta}) and tau pathologies are hallmarks of Alzheimers disease (AD) and they develop in human brain following differential spatiotemporal trajectories. As such, young/adult-onset tau-independent {beta}-amyloidosis is rare. We encountered four such cases among 397 banked brains, with the donors died of hematological malignances (blood cancers) or cardiovascular diseases. To explore the pathological implications, we examined 17 brains (10-87 year-old, y) from blood cancer patients and three (52-82 y) with cardiovascular diseases, focusing on vascular injury, axonal pathology and A{beta} formation. A{beta} plaques occurred in two adult brains (31 y, 63 y) with blood cancers and two (52 y, 65 y) with cardiovascular diseases in the absence of tau. In the blood cancer brains, 17/17 had vascular injuries seen in hematoxylin-eosin stained sections, 13/17 had iron leakage, and 13/17 had axonal pathology. Malignant cell infiltration was found in 5/14 brains with myeloid, lymphocytic and lymphoma malignances, with light chain infiltration in 3/3 brains with multiple myeloma. In the cardiovascular disease brains, A{beta} deposition primarily as diffuse plaques occurred in the cerebral cortex, with vascular and axonal pathologies in the white matter, striatum and internal capsule. Using a multi-labeling approach, the injury/stress induced axonal pathology was found to concur with {beta}-amyloid processor protein elevation and enhanced {beta}-secretase 1 processing but not intraneuronal A{beta} accumulation. The current findings suggest that hematological malignances and cardiovascular diseases are risk conditions for early-onset cerebral {beta}-amyloidosis, potentially attributable to vascular injury.

neuroscience↗

bioRxiv2025

Biochemical characterization and mucosal immune function of IgT in grass carp (Ctenopharyngodon idella)

Immunoglobulin T (IgT) is a teleost-specific immunoglobulin discovered to be specialized in mucosal immunity. For fish that live in water throughout their lives, eliciting a local mucosal immune response through immersion immunization is an important and highly suitable way for preventing fish diseases. However, due to the lack of corresponding antibodies against IgT, studies on its immune responses to pathogens and vaccines in commercial fish have largely been limited to rainbow trout. Thus, a valuable tool for assessing mucosal immune response to immersion vaccination is still lacking in most commercial fish species. In this study, we expressed and purified recombinant protein of the heavy chain constant domains (CH) 1-2 of grass carp IgT and immunized mice to develop a mouse anti-grass carp IgT monoclonal antibody (mAb). Western blotting results showed that the mAb could specifically recognize grass carp IgT without cross-reacting with grass carp IgM, IgMT1 or IgMT2. We then measured IgM and IgT concentrations in the serum and gill mucus of grass carp and examined the responses of specific IgM and IgT to immersion immunization with grass carp reovirus genotype (GCRV-) and Flavobacterium columnare. We found that the concentration of IgT in gill mucus was higher than that in serum, and the IgT/IgM ratio in gill mucus was much higher than that in serum. Moreover, after immersion immunization, the specific IgT levels in gill mucus increased significantly, while no specific IgT was detected in serum. In contrast, the specific IgM levels in serum increased significantly, whereas there was little change in specific IgM levels in gill mucus. These results indicated that IgT is an important immunoglobulin in mucosal immune response, whereas IgM plays an important role in systemic immune response in grass carp. In summary, these findings not only further elucidate the biochemical and functional differences between IgM and IgT in grass carp, but also provide a valuable detection tool for accurately evaluating the immune efficacy of immersion vaccines in grass carp.

immunology↗

bioRxiv2025

PlastidHub: an integrated analysis platform for plastid phylogenomics and comparative genomics

The plastome (plastid genome) represents an indispensable molecular data source for studying plant phylogeny and evolution. Although plastome size is much smaller than that of nuclear genome, accurate and efficient annotation and of use plastome sequences are not simple tasks. Therefore, a streamlined phylogenomic pipeline from plastome annotation to phylogenetic reconstruction and comparative genomics would greatly facilitate research using this important organellar genome. Here we develop PlastidHub, a new web application that primarily uses novel tools to analyze plastome sequences. In comparison with existing tools, new functionalities in PlastidHub include: (1) standardization of quadripartite structure; (2) improvement of annotation flexibility and consistency; (3) quantitative assessment of annotation completeness; (4) diverse extraction modes for canonical and specialized sequences; (5) intelligent screening of molecular markers for biodiversity studies; (6) visual comparison of structural variations and annotation completeness at the gene-level. PlastidHub has the following features: cloud-based web applications that do not require users to install, update, or maintain tools; detailed help documents including user guides, test examples, a static pop-up prompt box, and dynamic pop-up warning prompts when entering unreasonable parameter values; batch processing functionalities for all tools; intermediate result documents for secondary use; and easy-to-operate task flows between file upload and download. Interrelated task-based user interface design is the most important feature of PlastidHub. Give that PlastidHub is easy to use without specialized computational skills or resources, this new platform should become widely used among botanists and evolutionary biologists, improving and expediting research employing the plastome. PlastidHub is available at https://www.plastidhub.cn.

plant biology↗

bioRxiv2022

The gut microbiota promotes liver regeneration through hepatic membrane phospholipid synthesis

Background & AimsHepatocyte growth and proliferation is dependent on the synthesis of membrane phospholipids. Lipid synthesis, in turn, requires short chain fatty acids (SCFA) generated by bacterial fermentation, delivered through the gut- liver axis. We therefore hypothesized that dysbiotic insults like antibiotics treatment not only negatively affect gut microbiota, but also impair hepatic lipid synthesis and liver regeneration. MethodsStable isotope labelling and 70% partial hepatectomy (PHx) was carried out in C57Bl/6J wildtype mice, in mice treated with broad-spectrum antibiotics, in germfree mice and gnotobiotic mice colonized with minimal microbiota. Microbiome was analysed by 16S rRNA gene sequencing and microbial culture. Gut content, liver and blood were tested by lipidomics mass spectrometry, qRT-PCR, immunoblot and immunohistochemistry for expression of proliferative and lipogenic markers. Matched biopsies from hyperplastic and hypoplastic liver tissue of human patients subjected to portal vein embolization were analysed by qRT-PCR for lipogenic enzymes and results were correlated with liver volumetry. ResultsThree days of antibiotics treatment induced persistent dysbiosis with significantly decreased beta-diversity and richness, but massive increase of Proteobacteria, accompanied by decreased colonic SCFA. After PHx, antibiotics- treated mice showed delayed liver regeneration, increased mortality, impaired hepatocyte proliferation and decreased hepatic phospholipid synthesis. Expression of the key lipogenic enzyme SCD1 was upregulated after PHx, but delayed by antibiotics-treatment. Germfree mice essentially recapitulated the phenotype of antibiotics-treatment. Importantly, phospholipid synthesis, hepatocyte proliferation, liver regeneration and survival were rescued in gnotobiotic mice colonized with a minimal SCFA-producing microbial community. SCD1 was required for human hepatoma cell proliferation, and its hepatic expression was associated with liver regeneration and hyperproliferation in human patients. ConclusionGut microbiota are pivotal for hepatic membrane phospholipid synthesis and liver regeneration. Lay SummaryGut microbiota affects the liver lipid metabolism through the gut-liver axis, and microbial metabolites promote liver regeneration. Perturbations of the microbiome, e.g., by antibiotics treatment, impair the production of bacterial metabolites, which serve as building blocks for new membrane lipids in liver cells. As a consequence, hepatocyte growth and proliferation, and ultimately, liver regeneration and survival after liver surgery is impaired. HighlightsO_LIPartial hepatectomy in mice pretreated with antibiotics is associated with impaired hepatocyte proliferation and phospholipid synthesis, delayed liver regeneration and increased mortality C_LIO_LIThe delay in liver regeneration and impaired lipogenesis upon antibiotics treatment is preceded by dysbiosis of gut microbiota, increase of Proteobacteria and decreased short-chain fatty acids in the gut C_LIO_LIPartial hepatectomy in germfree mice essentially phenocopies the detrimental effects of antibiotic treatment C_LIO_LILiver regeneration and mortality, as well as phospholipid synthesis and hepatocyte proliferation in germfree mice are fully rescued upon colonisation with a minimal gut bacterial consortium capable of short-chain fatty acid production C_LIO_LIIn human patients, the intrahepatic expression of lipid synthesis enzymes positively correlates with proliferation and liver regeneration in the clinic C_LIO_LIThus, liver regeneration is affected by composition of gut microbiota C_LIO_LIClinically, pre-operative analysis of the gut microbiome may serve as biomarker to determine the extent of liver resections C_LI

cell biology↗

bioRxiv2022

Novel insights into L-serine exporters in Corynebacterium glutamicum from gene mining and functional analysis

Amino acid exporters play an important role in regulating amino acid production by Corynebacterium glutamicum, and over 90% of amino acid export is attributed to exporters in this species. ThrE was reported to be an O_SCPLOWLC_SCPLOW-serine exporter, and SerE was identified as an O_SCPLOWLC_SCPLOW-serine exporter in our previous study. However, when both ThrE and SerE were deleted, the O_SCPLOWLC_SCPLOW-serine titer was decreased by 60%, suggesting other O_SCPLOWLC_SCPLOW-serine exporters may exist. In the present study, NCgl0254 and NCgl0255 were identified as novel O_SCPLOWLC_SCPLOW-serine exporters through comparative transcriptomics and gene functional analyses. The contributions of the four exporters (ThrE, SerE, NCgl0254 and NCgl0255) in O_SCPLOWLC_SCPLOW-serine export were studied by gene deletion, gene overexpression, amino acid export assay and real-time quantitative PCR (RT-qPCR). The results showed that SerE is the major O_SCPLOWLC_SCPLOW-serine exporter in C. glutamicum. Fermentation and amino acid export assays of SSAAI, SSAAI-serE-thrE-ncgl0254-ncgl0255 and SSAAI{Delta}serE{Delta}thrE{Delta}ncgl0254{Delta}ncgl0255 indicated that the four O_SCPLOWLC_SCPLOW-serine exporters undertake most of the O_SCPLOWLC_SCPLOW-serine export, and their overexpression enhanced export of O_SCPLOWLC_SCPLOW-serine in SSAAI. When one O_SCPLOWLC_SCPLOW-serine exporter was deleted, the transcription level of the other three exporters was upregulated. However, the decrease in O_SCPLOWLC_SCPLOW-serine titer caused by deletion of one exporter was not fully compensated by upregulation of the other three exporters at the transcription level, indicating that O_SCPLOWLC_SCPLOW-serine production by C. glutamicum may be determined by cooperative efficiency of all four O_SCPLOWLC_SCPLOW-serine exporters, with each being interdependent. IMPORTANCEThis work identified the novel O_SCPLOWLC_SCPLOW-serine exporters NCgl0254 and NCgl0255, and revealed their roles in O_SCPLOWLC_SCPLOW-serine export alongside the O_SCPLOWLC_SCPLOW-serine exporters. All four O_SCPLOWLC_SCPLOW-serine exporters are interdependent and undertake most of the O_SCPLOWLC_SCPLOW-serine export, but SerE is the major O_SCPLOWLC_SCPLOW-serine exporter. The findings expand our knowledge of amino acid exporters in C. glutamicum, and the approach can be employed for exploring of bacterial exporters of unknown function.

bioengineering↗

bioRxiv2021

Whole-genome sequencing of Chinese native goat offers biological insights into cashmere fiber formation

Cashmere evolved naturally in the goat, and almost all breeds of goat can produce more or less cashmere fibers. However, the genetic alterations underlying cashmere trait selection are still unclear.We sequenced 120 Chinese native goat including two cashmere goat breeds (Ujumain, Chaidamu) and six ordinary goat breeds (Jining Gray, Matou, Guizhou Black, Jintang Black, Yunnan Black Bone, Chengdu Brown). The genome-wide selective sweep of cashmere goat and ordinary goat revealed a novel set of candidate genes as well as pathways, such as Nuclear factor kappa-B and Wnt Signaling pathways. Of them, the LHX2 gene regulating hair follicle development, was evident from the strongest selection signal when comparing the Uhumqin cashmere goat and ordinary goat. Interestingly, we identified a 582bp deletion at 367 kb upstream of LHX2 with higher frequency in cashmere goats and their ancient relatives. This mutation probably rises along the breeding procedures, and is putatively responsible for cashmere production and diameter, as revealed by association studies. Luciferase assay shows that the deletion, which acts as an insulator, restrains the expression of LHX2 by interfering its upstream enhancers.Our study discovers a novel insulator of the LHX2 involved in regulating cashmere production and diameter, which would be beneficial to understanding hair follicle development and regeneration. Our findings also provide new insights into the genetic formation of cashmere, and facilitate subsequent molecular breeding for cashmere goat improvement.

genomics↗

bioRxiv2020

Transcriptome analysis reveals the genetic basis underlying the development of skin appendages and immunity in hedgehog (Atelerix albiventris)

The expression of hair features is an evolutionary adaptation resulting from interactions between many organisms and their environment. Elucidation of the mechanisms that underlie the expression of such traits is a topic in evolutionary biology research. Therefore, we assessed the de novo transcriptome of Atelerix albiventris at three developmental stages and compared gene expression profiles between abdomen hair and dorsal spine tissues. We identified 328,576 unigenes in our transcriptome, among which 3,598 were differentially expressed between hair- and spine-type tissues. Dorsal and abdomen skin tissues 5 days after birth were compared and the resulting differentially expressed genes were mainly enriched in keratin filament, epithelium cell differentiation, and epidermis development based on GO enrichment analysis, and tight junction, p53, and cell cycle signaling pathways based on KEGG enrichment analysis. Expression variations of MBP8, SFN, Wnt10, KRT1, and KRT2 may be the main factors regulating hair and spine differentiation for the hedgehog. Strikingly, DEGs in hair-type tissues were also significantly enriched in immune-related terms and pathways with hair-type tissues exhibiting more upregulated immune genes than spine-type tissues. Thus, we propose that spine development was an adaptation that provided protection against injuries or stress and reduced hedgehog vulnerability to infection.

molecular biology↗

bioRxiv2019

Genotype Imputation and Reference Panel: A Systematic Evaluation

Here, 622 imputations were conducted with 394 customized reference panels for Han Chinese and European populations. Besides validating the fact that the imputation accuracy could always benefit from the increased panel size when the reference panel was population-specific, the results brought two new thoughts as follows. First, when the haplotype size of reference panel was fixed, the imputation accuracy of common and low-frequency variants (MAF>0.5%) decreased while the population-diversity of reference panel increased, but for rare variants (MAF<0.5%), a fraction of diversity (<20%) of panel could improve the imputation accuracy. Second, when the haplotype size of reference panel was increased with extra population-diverse samples, the imputation accuracy of common variants (MAF>5%) for European population could always benefit from the expanding sample size. But for Han Chinese population, the accuracy of all imputed variants reached the highest when reference panel contained a fraction of extra diverse sample (15%[~]21%). In addition, we evaluated the existing reference panels such as the HRC and 1000G Phase3 and CONVERGE. For European population, HRC was the best reference panel. For Han Chinese population, we proposed an optimum constituent ratio for the Han Chinese imputation if researchers would like to customize their own sequenced reference panel, but a high quality and large-scale Chinese reference panel was still needed. Our findings could be generalized to the other populations with conservative genome, a tool was provided to investigate other populations of interest (https://github.com/Abyss-bai/reference-panel-reconstruction).\n\nHighlights (Key points)O_LIA total of 394 reference panels were designed and customized by three strategies, and large-scale genotype imputations were performed with these panels for systematic evaluation in Han Chinese and European populations.\nC_LIO_LIThe accuracy of imputed variants reached the highest when reference panel contains a fraction of extra diverse sample (15%[~]21%) for Han Chinese population, if the haplotype size of the reference panel was increased with extra samples, which is the most common cases.\nC_LIO_LIThe imputation accuracy showed the different trends between Han Chinese and European populations. In a sense, the European genome may more diverse than Han Chinese genome by itself.\nC_LIO_LIExisting reference panels were not the best choice for Chinese imputation, a high quality and large-scale Chinese reference panel was still needed.\nC_LI

bioinformatics↗