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Biology subjects

Kang, F.

Publications and source records attributed to Kang, F..

8 recordsLinked to original sources

Reinnervation of Muscle Targets Enhances the Separability of Motor Unit Signals Following Peripheral Nerve Transfers

After amputation, advanced prosthetic limbs offer a promising means of restoring motor function. However, state-of-the-art prostheses often rely on aggregate electromyogram (EMG) signals to decode motor intention, which limits their ability to replicate natural limb movements. Decomposing EMG signals into individual motor unit components has shown potential for more natural control, but distinguishing between individual units can be challenging when nearby signals overlap. This study demonstrates that muscle target reinnervation surgeries can naturally increase physical separation between motor unit signals, thereby mitigating this overlap. Reinnervation of individual motor units is evaluated in a rodent hindlimb model after direct nerve-to-muscle implantation. Histological and electrophysiological analyses reveal that structural changes following reinnervation surgery result in beneficial motor unit signal changes, particularly improving spatial separation between motor unit signals compared to those in intact muscle. This spatial separation contributed to fewer instances of complex, overlapping signals in reinnervated muscle recordings. Motor unit signals were leveraged to provide a proof-of-concept of precise control of a virtual prosthesis for the first time after direct nerve-to-muscle implantation surgery. These findings highlight the potential of reinnervated muscle targets as key biological interfaces that facilitate motor unit separation, reducing the burden on decomposition algorithms and improving prosthetic control.

bioengineering↗

Single-Cell RNA Sequencing Reveals Hemocyte Heterogeneity, Differentiation Trajectories, and Viral Tropism in Shrimp (Macrobrachium rosenbergii) Infected with Decapod Iridescent Virus 1

Decapod Iridescent Virus 1 (DIV1) is a highly pathogenic virus threatening crustacean aquaculture. Hemocytes, the primary immune cells in shrimp, play crucial roles in host defense, yet their transcriptional heterogeneity and differentiation dynamics under viral infection remain poorly understood. Here, we characterize hemocyte subpopulations in Macrobrachium rosenbergii before and after DIV1 infection at single-cell resolution. We identified 12 distinct hemocyte clusters with unique molecular signatures. DIV1 infection induced significant shifts in hemocyte composition, with clusters 0, 5, 6, and 8 expanding, while clusters 9 and 10 exhibited resistance. Clusters 0, 5, and 8 were highly susceptible, showing elevated viral gene expression. Pseudo-time analysis revealed that DIV1 accelerates hemocyte differentiation, driving prohemocytes and semi-granulocytes toward terminally differentiated granulocytes and hyalinocytes, particularly the immune-active HC4 subpopulation. Functional enrichment analysis showed that susceptible hemocytes were associated with viral processes, oxidative stress, and phagocytosis, while resistant clusters exhibited distinct immune signatures. Furthermore, knockdown experiments confirmed the antiviral roles of PPO2, RAB11B, LAMP1, and Dorsal, as their silencing led to increased viral loads, higher MCP protein levels, and reduced shrimp survival. Taken together, our study provides the first single-cell resolution atlas of shrimp hemocytes under DIV1 infection, revealing their transcriptional heterogeneity, differentiation trajectories, and immune responses. These findings offer novel insights into shrimp antiviral immunity and lay the foundation for disease-resistant breeding and immunostimulatory strategies in aquaculture. ImportancesDecapod Iridescent Virus 1 (DIV1) is a highly pathogenic virus threatening crustacean aquaculture, causing severe economic losses. Hemocytes, the primary immune cells in shrimp, play crucial roles in antiviral defense, yet their diversity, differentiation, and responses to viral infection remain poorly understood. In this study, we employed single-cell RNA sequencing (scRNA-seq) to comprehensively characterize hemocyte subpopulations in Macrobrachium rosenbergii before and after DIV1 infection. We identified 12 transcriptionally distinct hemocyte clusters and revealed significant changes in hemocyte composition following infection. Notably, we discovered that specific clusters (0, 5 and 8) were highly susceptible to DIV1, while others (9 and 10) exhibited resistance. Additionally, we reconstructed hemocyte differentiation trajectories and found that DIV1 infection drives hematopoiesis, accelerating the transition of progenitor cells into terminally differentiated immune-active hemocytes. Functional analysis highlighted key antiviral effectors, including PPO2, RAB11B, LAMP1, and Dorsal, which were significantly upregulated in response to infection. These findings provide novel insights into shrimp antiviral immunity and viral pathogenesis, offering potential targets for disease-resistant breeding and immunostimulatory interventions.

immunology↗

White Spot Syndrome Virus Immediate-Early Protein (wsv100) Antagonizes the NF-kappaB Pathway to Inhibit Innate Immune Response in shrimp

Viruses have evolved sophisticated strategies to evade host immune defenses, often targeting conserved signaling pathways. In shrimp, the NF-{kappa}B signaling pathway is crucial for antiviral immunity, yet its regulation during White Spot Syndrome Virus (WSSV) infection remains poorly understood. Here, we identify and characterize wsv100, an immediate-early (IE) protein of WSSV, as a key antagonist of the NF-{kappa}B pathway. wsv100 interacts directly with the transcription factor Dorsal and the adaptor protein IMD, preventing Dorsal phosphorylation by Pelle kinase. This inhibition suppresses Dorsals nuclear translocation and downstream expression of antimicrobial peptides (AMPs), essential for antiviral defense. Knockdown of wsv100 reduced WSSV replication, increased Dorsal phosphorylation, and enhanced AMP expression, leading to higher survival rates in infected shrimp. Conversely, wsv100 overexpression promoted WSSV replication and AMPs suppression. These findings reveal a novel immune evasion mechanism by which WSSV subverts the NF-{kappa}B pathway and highlight the evolutionary arms race between hosts and viruses. This study enhances our understanding of host-virus interactions and offers potential targets for antiviral strategies in shrimp aquaculture. Author SummaryThe innate immune system is the first line of defense against viral infections in invertebrates, with the NF-{kappa}B signaling pathway playing a central role in orchestrating antiviral responses. In this study, we uncover a novel immune evasion mechanism employed by White Spot Syndrome Virus (WSSV), a devastating pathogen in shrimp aquaculture. The WSSV immediate-early protein wsv100 directly targets the transcription factor Dorsal and prevents its phosphorylation by Pelle kinase, a critical step in NF-{kappa}B activation. This interaction suppresses Dorsals nuclear translocation and downstream expression of antimicrobial peptides (AMPs), thereby impairing the shrimps ability to mount an effective immune response. Knockdown of wsv100 significantly reduced WSSV replication and enhanced shrimp survival, while wsv100 overexpression had the opposite effect. These findings not only elucidate how WSSV exploits the NF-{kappa}B pathway but also underscore its central role in shrimp antiviral immunity. This work advances our understanding of host-virus co-evolution and provides a foundation for developing novel antiviral strategies to mitigate the economic losses caused by WSSV in shrimp aquaculture.

microbiology↗

Global analysis of the yeast knock-out phenome

Genome-wide phenotypic screens in the budding yeast Saccharomyces cerevisiae have produced the largest, richest and most systematic phenotypic description of any organism. Such an achievement was enabled by the development of highly scalable phenotypic assays and construction of the yeast knock-out (YKO) collection, comprising ~5,000 isogenic strains each deleted for exactly one open reading frame. Systematic screening of the YKO collection led to ~500 publications describing ~14,500 phenotypes capturing nearly every aspect of yeast biology. Yet, integrative analyses of this rich data source have been virtually impossible due to the lack of a central repository and consistent meta-data annotations. Here, we describe the aggregation, harmonization and analysis of all published phenotypic screens of the YKO collection, which we refer to as the Yeast Phenome (www.yeastphenome.org). To demonstrate the power of data integration and illustrate how much it facilitates the generation of testable hypotheses, we present three discoveries uniquely enabled by Yeast Phenome. First, we use the variation in the number of phenotypes per gene to identify tryptophan homeostasis as a central point of vulnerability to a wide range of chemical compounds, including FDA-approved drugs. Second, using phenotypic profiles as a tool for predicting gene function, we identify and validate the role of YHR045W as a novel regulator of ergosterol biosynthesis and DNA damage response, and YGL117W as a new member of the aromatic amino acid biosynthesis pathway. Finally, we describe a surprising exponential relationship between phenotypic similarity and intergenic distance in both yeast and human genomes. This relationship, which stretches as far as 380 kb in yeast and 100 Mb in humans, suggests that gene positions are optimized for function to a much greater extent than appreciated previously. Overall, we show that Yeast Phenome enables systematic enquiries into the nature of gene-gene and gene-phenotype relationships and is an important new resource for systems biology.

systems biology↗

Ultra-small bispecific fusion protein augments tumor penetration and treatment efficacy for pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer-related deaths. Due to drugs low intrinsic anticancer activity and the unique physiological barrier of PDAC tumors, the once highly anticipated antibody-based pathway-targeted therapies have not achieved promising improvement in outcomes. Here, an ultra-small-sized bispecific fusion protein, termed Bi-fp50, that could largely enrich deep tumor tissue and effectively inhibit PDAC tumor growth was reported. The bispecific Bi-fp50 protein was constructed by a typical synthetic biology method that could efficiently target EGFR and VEGF of PDAC cells simultaneously in vitro and in vivo. For Bxpc3 and Aspc1 PDAC cells, the Bi-fp50 achieved a significant and synergistic therapeutic effect. Owing to the small size of only 50 kDa and the function of reducing the interstitial fluid pressure by vascular normalization, the Bi-fp50 showed enhanced penetration, considerable accumulation, and uniform distribution in tumor and subsequently led to effective inhibition of the growth of Bxpc3 cells-induced PDAC tumor in vivo. Furthermore, no noticeable side effect of Bi-fp50 was found in vitro and in vivo. This work demonstrates that the synthetic Bi-fp50 fusion protein could be used as a new effective pathway-specific targeted therapy for PDACs.

cancer biology↗

Planting graphene quantum dots in PEGylated nanoparticles for enhanced and multimodal in vivo imaging of tumor

Photoluminescent graphene quantum dots (GQDs) have recently attracted considerable attention for biomedical applications owing to the interesting physicochemical and photophysical properties, and prominent biocompatibility and biosafety. However, although much progress has been achieved in therapy and in vitro bioimaging, broad and crucial in vivo fluorescence bioimaging and synergistically working with other nanomedicine are very challenging and limited. Herein, we in situ implanted GQDs in the PEGylated layer of nanoparticles (NPs) via a bottom-up approach to obtain the NPs (core)-GQDs-PEG multifunctional nanoprobe (NPC-GQDs-PEG), which prolonged the blood circulation of GQDs more than four times and increased the tumor accumulation 7~8 times than GQDs used alone. Under assisted by the flexible microscope, the GQDs were successfully used for in vivo real-time monitoring of local NPs pharmacokinetics, in vivo multimodality imaging, and fluorescence imaging-guided tumor surgery. The approach of implanting GQDs in PEGylated nanomedicine and synergistic working provide a new strategy for in vivo biomedical applications of GQDs.

cancer biology↗

Taxonomy Analysis in Bacteria Kingdom based onProtein Domain: A Comparison Study

The taxonomy research on the bacterial kingdom is important and can be usually conducted by the analysis on conserved genes, 16s rRNA, protein domain, and so on. Comparatively, the protein domains maintain a most direct relationship with phenotypes. In this paper, based on the protein domain, we propose a 3-step framework to standardize the classification process of bacteria. Different model candidates are involved and discussed in each step. By comparing the classification results with existing taxonomy, we select the most appropriate candidate to improve the framework, and furthermore, discuss their biological significance. Finally, we put forward taxonomy suggestions based on the best classification results. Significance StatementWe standardize a 3-step framework to carry out bacterial taxonomy research based on protein domain. Furthermore, we filter out the best solution in each step that can together generate the most appropriate classification result, and at the same time, we discuss the biological significant it indicates. Finally, we propose suggestions on NCBI bacterial taxonomy based on the classification results.

bioinformatics↗

Assessment of the aging of the brown adipose tissue by 18F-FDG PET/CT imaging in the progeria mouse model LmnaG609G/G609G

Brown adipose tissue (BAT) is an important energy metabolic organ that is closely related to obesity, type 2 diabetes, and atherosclerosis. Aging is one of the most important determinants of BAT activity. In this study, we used 18F-FDG PET/CT imaging to assess the aging of the BAT in LmnaG609G/G609G mice. To evaluate the BAT activity, LmnaG609G/G609G and wild-type (WT) mice were injected with 18F-FDG, and PET/CT imaging was performed. The maximum standardized uptake value (SUVMax) of the BAT was measured and the target/nontarget (T/NT) values of BAT were calculated. The transcription and the protein expression levels of the uncoupling protein 1 (UCP1), beta3-adrenergic receptor ({beta}3-AR), and the PRdomain-containing16 (PRDM16), were measured by quantitative real-time polymerase chain reaction (RT-PCR) and Western blotting or immunohistochemical analysis. Apoptosis and cell senescence of the BAT, in WT and LmnaG609G/G609G mice, was detected by Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and by CDKN2A/p16INK4a immunohistochemical staining, respectively. At 14 weeks of age, the BAT SUVMax and the expression levels of UCP1, {beta}3-AR and PRDM16 in LmnaG609G/G609G mice was significantly lower than that in WT mice. At the same time, the number of p16INK4a and TUNEL positively stained cells (%) increased in LmnaG609G/G609G mice. LmnaG609G/G609G mice are an ideal model for studying BAT aging. The aging characteristics and the aging mechanism of BAT in LmnaG609G/G609G mice can mimic normal BAT aging.

cell biology↗