Biology subjects

Zhu, Y.

Publications and source records attributed to Zhu, Y..

At least 217 records · Page 12Linked to original sources

bioRxiv2025

HPInet: Interpretable prediction of Host-Pathogen protein-protein Interactions using a transformer-based neural network

Gram-negative bacteria utilize a series of secretion systems (T1SS-T10SS) to deliver secreted effector proteins (T1SE-T10SE) into host cells, leading to infections and diseases. Understanding the interactions between these effector proteins and host proteins is crucial for unraveling the pathogenic mechanisms of bacterial pathogens. Despite advancements in sequencing technologies that have significantly enhanced our knowledge of effector protein diversity and structure, the molecular mechanisms underlying their interactions with human host proteins remain unclear. Experimental approaches to validate these interactions are labor-intensive, time-consuming, and insufficient to comprehensively map the extensive effector-host protein interaction (PPI) network. Additionally, specialized computational tools for predicting these interactions remain scarce. To address this gap, we developed HPInet, a transformer-based deep learning model for predicting interactions between bacterial effector proteins and human host proteins. HPInet introduces convolutional layers and global response normalization (GRN) into the feed-forward network (FFN) of the transformer architecture, enhancing the extraction of local sequence features. Compared to existing state-of-the-art methods, HPInet significantly improves prediction performance, increasing accuracy from 0.502 to 0.891 and boosting sensitivity by 35.3%. Furthermore, by leveraging the models attention mechanism, HPInet identifies critical residues at interaction sites, demonstrating its capability to capture local structural features of PPI sites solely from sequence information. To facilitate its application in research, HPInet has been implemented as a freely accessible web server available at https://bis.zju.edu.cn/hpinet. This platform provides a powerful and interpretable tool for studying effector-host protein interactions, offering valuable insights into bacterial pathogenesis and potential therapeutic targets.

bioinformatics↗

bioRxiv2025

Differential effects of HDAC inhibitors in the RhoI255d mouse model for autosomal dominant retinitis pigmentosa

Retinitis Pigmentosa (RP) is an inherited neurodegenerative disease which leads to loss of retinal photoreceptors and blindness. Histone deacetylases (HDAC) were previously found to be involved in photoreceptor cell death, and HDAC inhibitors have shown protective effects in animal models for autosomal recessive RP. However, whether HDAC inhibitors can protect photoreceptors in autosomal dominant RP (ADRP) remains unclear. Here, we utilized the recently generated human homologous RhoI255d/+ ADRP mouse model to investigate degenerative mechanisms and the therapeutic potential of HDAC inhibitors. To visualize photoreceptor HDAC activity, we applied an in situ HDAC activity assay on post-natal (P) day 20 wild type (WT) and RhoI255d/+ retina. Treatment with the HDAC class I/II inhibitor Trichostatin A and the HDAC class III inhibitor nicotinamide (NAM) suggested that most HDAC activity detected in RhoI255d/+ photoreceptors was related to class I/II isoforms. The therapeutic potential of different HDAC inhibitors, targeting different HDAC isoforms, was evaluated on organotypic retinal explants cultured under completely controlled conditions. HDAC inhibitors tested included SAHA (Vorinostat), MPT0G211, ACY-957, and NAM. Readouts comprised the TUNEL assay, immunostaining for activated calpain-2 and caspase-3, cone arrestin-3, and bromodeoxyuridine (BrdU)-labeling. Among the compounds tested, MPT0G211, targeting predominantly cytoplasmic HDAC-6, exhibited the strongest protective effect on both rod and cone photoreceptors. Remarkably, ACY-957, inhibiting nuclear HDAC-1/-2, at higher concentration induced both photoreceptor cell death and cell proliferation. High levels of NAM, blocking mitochondrial and nuclear HDACs, caused selective rod cell death, without affecting cones. All HDAC inhibitors tested had no or only minor effects on neurons of the inner retina. Our study highlights the complexity of HDAC activity during photoreceptor neurodegeneration and cautions against the use of unspecific inhibitors. At the same time, it showcases important differences between rod and cone photoreceptors and suggests especially HDAC-6 as a potential target for future therapy development. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=163 SRC="FIGDIR/small/666875v1_ufig1.gif" ALT="Figure 1"> View larger version (59K): org.highwire.dtl.DTLVardef@598681org.highwire.dtl.DTLVardef@18d8ba4org.highwire.dtl.DTLVardef@1cacb24org.highwire.dtl.DTLVardef@dec519_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2025

Palmitoylation-dependent activation of NADK promotes NADP+ synthesis and tumorigenesis

NAD kinase (NADK) is the sole cytosolic enzyme that catalyzes the synthesis of nicotinamide adenine dinucleotide phosphate (NADP+) from NAD+. NADP+ is essential for anabolic reactions and redox balance. Here, we show that palmitate facilitates NADP+ synthesis by enhancing NADK palmitoylation and activity. NADK is post-translationally S-palmitoylated on three cysteine residues (Cys22, Cys23, and Cys26) within the amino-terminal domain by the protein-acyl transferase ZDHHC5, which stimulates NADK activity. Fatty acids activate NADK by enhancing its palmitoylation and relief of an autoinhibitory function inherent to its amino terminus. Furthermore, ZDHHC5-/- mice showed defect in NADK palmitoylation and NADP+ production. Clinically, elevated expression of ZDHHC5 in pancreatic cancer patients was associated with increased NADK palmitoylation and correlated with poor prognoses for patients. These data reveal that fatty-acid and ZDHHC5-mediated palmitoylation has a critical role in NADP+ synthesis and cancers.

cancer biology↗

bioRxiv2025

Cortical excitatory and inhibitory neuron deficits may underlie the cognitive and social impairments in a mouse model of schizophrenia with exonic Reln deletion

Reelin is an essential extracellular matrix glycoprotein involved in the formation of cortical layers and has been associated with several neuropsychiatric conditions, such as schizophrenia (SCZ). To explore its role in brain function and its potential involvement in SCZ, we developed a Reln heterozygous deletion (Relndel/+) mouse model that mimics a genetic deletion observed in a Japanese patient with SCZ. In previous studies, we demonstrated that Relndel/+ mice exhibit cognitive impairments in a visual discrimination test. Here, we found that Relndel/+ mice displayed impairments in social novelty recognition, while social preference remained intact. Immunohistochemical analyses revealed a significant decrease in the numbers of calcium/calmodulin-dependent protein kinase II (CaMKII)-positive glutamatergic pyramidal neurons, gamma-aminobutyric acid (GABA)-ergic interneurons, and parvalbumin (PV)-positive interneurons in the medial prefrontal cortex (mPFC) of Relndel/+ mice. Furthermore, Relndel/+ mice exhibited significant deficits in excitatory spine density and morphology, as well as a decrease number of PV boutons in the mPFC compared to wild-type (WT) mice. Finally, we demonstrated that injection of AAV-R36-Myc virus into the mPFC can improve social novelty impairments in Relndel/+ mice, but no effects on WT control. These findings indicate that Relndel/+ mice could be a valuable model for exploring the neurobiological mechanisms underlying cognitive and social impairments in SCZ. Futhermore, our results with AAV-R36-Myc also suggest the therapeutic potential of Reelin replacement, warranting further investigation as a possible treatment strategy for SCZ. HighlightsO_LIReelin deficiency disrupts social novelty, but not social preference, in Relndel/+ mice C_LIO_LIRelndel/+ mice serve as a novel model to investigate impairments of neuronal mechanisms on schizophrenia C_LIO_LIAAV-R36-myc injection rescues social novelty deficits in Relndel/+ mice C_LIO_LIReelin replacement therapy is a potential treatment for schizophrenia C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=143 HEIGHT=200 SRC="FIGDIR/small/666057v1_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@1f4921aorg.highwire.dtl.DTLVardef@1a41b33org.highwire.dtl.DTLVardef@f5f2bcorg.highwire.dtl.DTLVardef@1134d8d_HPS_FORMAT_FIGEXP M_FIG C_FIG

animal behavior and cognition↗

bioRxiv2025

Multifunctional Injectable GelMA Hydrogels with MSN-Mediated Spatiotemporal Icariin Release for Enhanced Osseointegration in Bone Defects

The repair of bone defects is faced with the dual challenges of limited autograft donors and single function of artificial materials. The development of new materials with mechanical adaptability, drug-controlled release and osteogenic induction has become a research hotspot in bone tissue engineering. Here, we developed an injectable photocrosslinkable hydrogel by integrating icariin (ICA)-loaded mesoporous silica nanoparticles (MSN) into gelatin methacryloyl (GelMA). The amino-functionalized MSN enhanced compressive modulus by 1.5-fold (p < 0.05) and enabled pH-responsive ICA release (91.2{+/-}4.2% cumulative release over 15 days). Our in vitro findings revealed the composite hydrogel promoted BMSC proliferation was 1.43{+/-}0.04 times that of GelMA group. And express excellent osteogenic differentiation ability (ALP activity: 3.25-fold; Mineralization: 5.01-fold). In vivo study, Micro-CT revealed significantly higher bone volume fraction (BV/TV) in rat calvarial defects at 12 weeks, with histology confirming mature trabecular bone formation. This MSN-mediated spatiotemporal delivery system synchronizes immunomodulation and osteogenesis, offering a promising strategy for non-load-bearing osseointegration.

bioengineering↗

bioRxiv2025

Formulation and Characterization of Primary Tissue-Derived Microfluidic Droplet-Engineered Organoids

Organoid technology offers a powerful platform for modeling human tissues, studying disease mechanisms, and developing personalized therapies. However, widespread clinical application is hindered by challenges in scalability, reproducibility, and the handling of ultra-small tissue samples typical of clinical biopsies. Here, we present a comprehensive and automated protocol for the formulation and characterization of microfluidic droplet-engineered organoids (DEOs) derived from primary tissue samples. This protocol integrates 3 key stages: (1) Extraction and purification of viable primary cells from ultra-small tissue specimens using the small-Tissue Extraction Device (sTED); (2) High-throughput fabrication of uniform cell-laden microspheres using an integrated microfluidic bioprinter (OrgFab), capable of generating over 100 organoids from just 10 L of bioink; and (3) Rapid organoid characterization using lamination-based processing for single-cell analysis while preserving spatial context. The automated workflow minimizes manual intervention, reducing variability and enhancing reproducibility, making it suitable for high-throughput applications such as drug screening and disease modeling. Our method allows for the generation of patient-derived organoids that closely mimic the native tissue microenvironment, including diverse cell types and structural features, within a significantly reduced timeframe. This 3 stage protocol enhances the use of organoids in personalized medicine by enabling the rapid assessment of drug efficacy in patient-specific models. Here, the integration of advanced techniques supports existing organoid protocols, providing a valuable resource for researchers and clinicians seeking to improve patient outcomes through more efficient and precise organoid-based applications.

bioengineering↗

bioRxiv2025

Pluripotent stem cell-derived siTNK cells attack tumors via a synthetic CD8-CD28 TCR complex

Tumor-associated antigen-specific T cell receptor (TCR)-engineered T cells offer a promising strategy for cancer therapy. Natural killer (NK) cells exhibit broad anti-tumor activity with low side effects but lack the capacity to recognize intracellular antigens. Here, we found that the human pluripotent stem cell (hPSC)-derived iNK cells, unlike tissue-isolated NK cells, expressed all four CD3 subunits at the transcriptome level. We introduced a synthetic gene-expressing complex (SCOTR), encoding a tumor antigen- specific TCR, CD8 coreceptor, and CD28 costimulatory molecule, into hPSCs to generate SCOTR-hPSCs. The SCOTR-hPSCs gave rise to abundant synthetic TCR complex-expressing iNK (siTNK) cells via an organoid induction method. These siTNK cells showed HLA-dependent, antigen-specific cytotoxicity against tumor cells and significantly suppressed tumor growth in tumor xenograft animal models, while also preserving universal non-specific tumor-killing activity. Collectively, siTNK cells, as hPSC-derived hybrid cells with dual features of adaptive T and inherent NK cells, offer an artificial cell source for human immunotherapies.

immunology↗

bioRxiv2025

The neuroimaging correlates of depression established across six large-scale datasets

Neuroimaging data offers noninvasive insights into the structural and functional organization of the brain and is therefore commonly used to study the neuroimaging correlates of depression. To date, a substantial body of literature has suggested reduced size of subcortical regions and abnormal functional connectivity in frontal and default mode networks linked to depression. However, recent meta analyses have failed to identify significant converging correlates of depression across the literature such that a conclusive mapping of the neuroimaging correlates of depression remains elusive. Here we leveraged 23,417 participants across six datasets to comprehensively establish the neuroimaging correlates of depression. We found reductions in gray matter volume/ cortical surface area associated with depression in the frontal cortex, anterior cingulate, and insula, confirming prior studies showing the importance of prefrontal and default mode regions in depression. Our findings demonstrate multiple surprising results, including a lack of depression correlates in subcortical brain regions, significant depression correlates in somatomotor and visual regions, and limited functional connectivity findings. Overall, these results shed new light on key brain regions involved in the pathophysiology of depression, updating our understanding of the neuroimaging correlates of depression. We anticipate that these insights will inform further research into the role of sensorimotor and visual regions in depression and into the impact of heterogeneity on functional connectivity correlates of depression.

neuroscience↗

bioRxiv2025

Buffer Valency Engineering Enables High-concentration and Shelf-stable DNA Transfection Particles for Viral Vector Production

Cost-effective and scalable production is critical for advancing the clinical translation of adeno-associated virus (AAV)-mediated gene therapy. The widely used transient transfection method using plasmid DNA (pDNA)-loaded transfection particles for AAV production faces technical challenges due to instability of the particles and the concentration limits for particle preparation, hindering reproducibility and scalability. Here, we report a streamlined and scalable strategy to generate shelf-stable, highly concentrated pDNA/poly(ethylenimine) (PEI) transfection particles. By incorporating trivalent citrate ions in the dilution buffers, we kinetically modulate electrostatic complexation to achieve uniform nanoparticle assembly and prevent aggregation at high concentrations. This enables a tenfold increase in pDNA concentration in stabilized transfection particles from a typical range of 10-20 g/mL to 200 g/mL, while reducing the required dosing volume from 5-10% to 0.5% of the cell culture medium. The particle assembly process is robust to changes in mixing scale and timing and is compatible with standard workflows. We demonstrate equivalent AAV production efficiencies to standard methods and consistent performance in various production scales, which confirms the practical utility of this assembly method in developing robust, scalable, and cost-effective AAV manufacturing processes.

biochemistry↗

bioRxiv2025

A Compact Two-Photon Module for Simultaneous Dual-Depth, Multi-Region in vivo Brain Imaging

Understanding how distributed brain regions interact across cortical depths is crucial for uncovering the neural basis of behavior and cognition. Two-photon microscopy (2PM) excels at imaging the superficial layer, while three-photon microscopy (3PM) penetrates deep tissues but lacks sufficient speed for capturing fast superficial dynamics. Here, we present a compact two-photon imaging module (2PIM) that seamlessly integrates with existing 3PM to achieve simultaneous, high-speed imaging of superficial and deep brain regions, while preserving the deep tissue penetration of 3PM. This dual-modality system allows for remote and independent control of imaging planes in both axial and lateral dimensions. Leveraging this technology, we discovered context-dependent modulation of hippocampal CA1 and visual cortex responses to identical tactile stimuli, layer-specific temporal dynamics in sensory cortex during air puff stimulation, and depth-divergent neuronal activity patterns in motor cortex across acute-to-chronic pain. These results highlight the systems potential for dissecting the spatiotemporal coordination of distributed brain circuits.

bioengineering↗

bioRxiv2025

Cortex-Wide, Cellular-Resolution Volumetric Imaging with a Modular Two-Photon Imaging Platform

Mapping cortex-wide neuronal activity at single-cell resolution has been limited by the physical trade-off between numerical aperture and field-of-view (FOV) in two-photon microscopes. We present Meso2P, a modular two-photon platform that decouples excitation and detection by introducing a lateral paraboloid fluorescence collector. The design sustains an effective NA 0.87 over a contiguous 6 x 6 mm2 FOV at high speed (2,048 x 2,048 pixels at 7.67 Hz). The modular platform can be upgraded with optional modules for simultaneous multi-plane imaging (1-4 planes at full resolution and speed), volumetric imaging (6 x 6 x 0.5 mm3, 2,048 x 2,048 x 28 voxels at 1 Hz capturing> 210,000 neurons), and holographic two-photon optogenetic stimulation for targeted perturbations. To handle the resulting large-scale data, we provide an open-source deep-learning pipeline that automates motion correction, segmentation, and spike inference. We demonstrate cortex-wide sensory responses, layer-specific network synchrony during anaesthesia, and in-vivo tracking of micro and nanoplastic distribution. Meso2P therefore provides a reproducible route to high-throughput volumetric imaging across almost the entire cortex with high detection efficiency.

neuroscience↗

bioRxiv2025

Genetic mapping of lifespan and mitochondrial stress response in C. elegans

The mitochondrial unfolded protein response (UPRmt) is one of the mito-nuclear regulatory circuits that restores mitochondrial function upon stress conditions, promoting metabolic health and longevity. However, the complex gene interactions that govern this pathway and its role in aging and healthspan remain to be fully elucidated. Here, we activated the UPRmt using doxycycline (Dox) in a genetically diverse C. elegans population comprising 85 strains and observed large variation in Dox-induced lifespan extension across these strains. Through multi-omic data integration, we identified an aging-related molecular signature that was partially reversed by Dox. To identify the mechanisms underlying Dox-induced lifespan extension, we applied quantitative trait locus (QTL) mapping analyses and found one UPRmt modulator, fipp-1/FIP1L1, which was functionally validated in C. elegans and humans. In the human UK Biobank, FIP1L1 was associated with metabolic homeostasis, underscoring its translational relevance. Overall, our findings demonstrate a novel UPRmt modulator across species and provide insights into potential translational research.

genetics↗

bioRxiv2025

Modular Inter-brain Synchrony Network Associated with Social Difficulty in Autism Spectrum Disorder: a Graph Neural Network-Driven Hyperscanning Study

Understanding social difficulties in Autism Spectrum Disorder (ASD) remains challenging due to its neurobiological heterogeneity and the limited ecological validity of conventional neuroimaging methods in capturing dynamic social interactions. Hyperscanning analysis based on functional near-infrared spectroscopy (fNIRS), which measures inter-brain synchrony (IBS) during dyadic interaction, offers a novel avenue to address these challenges. However, prior studies on ASD have reported inconsistent findings, primarily focusing on intra-regional synchronization while overlooking cross-regional network dynamics. To bridge this gap, we proposed an interpretable graph neural network (GNN) model to systematically identify ASD-specific IBS modular network between child-caregiver dyads during naturalistic cooperative puzzle-solving and free-talking tasks. We identified distinctive key IBS sub-networks for the cooperative puzzle-solving task and free-talking task, with the frontal eye field (FEF) of caregivers, the dorsal lateral prefrontal cortex (DLPFC) and the motor region of children highlighted. Furthermore, the key IBS sub-networks were found to be able to predict multiple domains of the core ASD symptoms. By integrating hyperscanning with GNN-driven analysis, this work uncovers task-dependent inter-brain neural mechanisms underlying social difficulties in ASD. These findings advance the field by proposing a data-driven framework to identify IBS biomarkers tied to clinical profiles, paving the way for personalized interventions that integrate computational neuroscience with clinical practice.

neuroscience↗

bioRxiv2025

The bifunctional dynamin-like GTPase switch DynAB modulates both vegetative and sporulation cell division in Streptomyces.

As part of their complex developmental lifecycle, the multicellular filamentous bacteria Streptomyces have evolved two modes of cell division distinct from binary fission. In vegetative cell division, irregularly spaced cross-walls form within vegetative hyphae, whereas in sporogenic hyphae, regularly spaced sporulation septa form synchronously, leading to spore formation. However, the mechanisms controlling these processes largely remain unknown. The bacterial dynamin-like protein pair DynAB was previously reported to be a component of sporulation septa. Here, we reveal that DynA and DynB have critical roles in both cell division modes, regulating the formation of sporulation septa and cross-walls, with the Streptomyces cell division protein SsgB modulating their activities. dynAB deletion and overexpression, respectively, increased and abrogated cross-wall formation in vegetative hyphae, and Streptomyces DynAB also inhibited cell division in Escherichia coli, resulting in formation of unicellular filamentous cells and suggesting an ancient and conserved function for these proteins. Notably, SsgB could relieve the inhibition of cell division by DynAB in both Streptomyces and E. coli. In contrast to DynAB, SsgB overexpression generated spore-like compartments in vegetative hyphae, a phenomenon that required disruption of the DynAB complex. Fluorescent tags revealed dynamic localization of DynAB during development, and further analyses indicated that, in sporogenic hyphae, the timing of DynAB expression, their GTP-binding activity, and interaction with SsgB were associated with the synchronous initiation of sporulation septation. Our findings establish DynAB as an integrator of spatiotemporal cues in bacterial multicellularity and provide insights into the evolution of complex cell cycle regulation in prokaryotes. SignificanceThe evolution of multicellularity in bacteria involved the development of complex mechanisms to spatially and temporally coordinate cell division. Streptomyces, renowned for their production of bioactive secondary metabolites, exemplify bacterial complexity. This study reveals how Streptomyces employ the dynamin-like proteins DynAB as a bifunctional molecular switch, enabling transition between vegetative and reproductive growth through integrated interactions with developmentally regulated proteins and the availability of the energy supplier GTP. Importantly, DynAB could repress cell division in both Streptomyces and Escherichia coli, suggesting an evolutionary origin of these proteins prior to bacterial multicellularity. Our work reveals the dual function and switch mechanism of DynAB in Streptomyces, providing insights into the emergence of dynamic cell cycle control in prokaryotes.

microbiology↗

bioRxiv2025

Homodimerized Arpins: Binding to Arp2/3 Complexes with Positive Synergy to Inhibit Lamellipodia-Dependent Tumor Metastasis

The Arp2/3 complex is a central regulator of actin polymerization dynamics and cancer cell motility, with its dysregulation implicated in metastasis and therapeutic resistance. Despite its therapeutic potential, targeting Arp2/3 remains challenging due to the lack of precise molecular insights into endogenous inhibitors. Arpin, a lamellipodia-localized Arp2/3 inhibitor, has emerged as a critical modulator of cancer migration; however, the structural and mechanistic basis of its inhibitory function remains unresolved. Here, we report the 1.65-[A] crystal structure of Arpins N-terminal globular domain, revealing a unique structural fold distinct from all known Arp2/3-binding factors. Structural and biophysical analyses demonstrate that Arpin forms homodimers via a conserved interface, which is essential for cooperative inhibition of Arp2/3-dependent actin polymerization. Functional studies in cancer models reveal that Arpin homodimerization potently suppresses lamellipodia-driven migration and invasion, effects further enhanced by engineered dimeric constructs or artificially designed dual-tailed peptides. These findings elucidate a structural basis for Arpin-mediated suppression of cancer cell motility and identify homodimeric cooperativity as a druggable mechanism for targeting metastatic progression. Our work provides a molecular framework for designing Arpin-inspired inhibitors to counteract therapeutic resistance and metastasis in cancers reliant on Arp2/3-driven actin dynamics.

cancer biology↗

bioRxiv2025

β2AR Agonists Sustain Thermogenesis and Leanness via Sympathofacilitation

Human thermogenesis depends on {beta}2-adrenoceptors ({beta}2AR) expressed in thermogenic adipocytes, which are activated by norepinephrine released from sympathetic neurons. Whether {beta}2AR also modulates thermogenesis via direct presynaptic action within sympathetic neurons has remained unclear. Here, we identify Adrb2 expression in human and rodent cervical sympathetic neurons. {beta}2AR agonism exerts neurotrophic effects and facilitates cholinergic responsiveness in mouse sympathetic neurons, indicating a sympathofacilitatory role. Selective deletion of {beta}2AR in sympathetic neurons leads to impaired nerve activity in brown adipose tissue, sympathetic neuropathy, worsened fasting-induced hypothermia, and progressive obesity in chow-fed mice--without changes in food intake. These findings uncover a presynaptic role for {beta}2AR in sustaining thermogenesis and regulating adiposity, suggesting sympathofacilitation as a therapeutic avenue for obesity. HighlightsO_LIHuman and mouse cervical sympathetic neurons express adrenoceptor beta 2 (Adrb2) C_LIO_LI{beta}2-adrenoceptor ({beta}2AR) activation is neurotrophic and facilitates sympathetic neuronal excitability C_LIO_LILoss of {beta}2AR in sympathetic neurons leads to neuropathy in brown adipose tissue and reduced sympathetic activity C_LIO_LIDeletion of {beta}2AR in sympathetic neurons exacerbates fasting-induced hypothermia and promotes obesity independently of food intake C_LI

physiology↗

bioRxiv2025

Image-Based Meta- and Mega-Analysis (IBMMA): A Unified Framework for Large-Scale, Multi-Site, Neuroimaging Data Analysis

The increasing scale and complexity of neuroimaging datasets aggregated from multiple study sites present substantial analytic challenges, as existing statistical analysis tools struggle to handle missing voxel-data, suffer from limited computational speed and inefficient memory allocation, and are restricted in the types of statistical designs they are able to model. We introduce Image-Based Meta- & Mega-Analysis (IBMMA), a novel software package implemented in R and Python that provides a unified framework for analyzing diverse neuroimaging features, efficiently handles large-scale datasets through parallel processing, offers flexible statistical modeling options, and properly manages missing voxel-data commonly encountered in multi-site studies. IBMMA produced stronger effect sizes and revealed findings in brain regions that traditional software overlooked due to missing voxel-data resulting in gaps in brain coverage. IBMMA has the potential to accelerate discoveries in neuroscience and enhance the clinical utility of neuroimaging findings.

neuroscience↗

bioRxiv2025

Deciphering the microbial landscape of lower respiratory tract in health and respiratory diseases

The microbiota plays an important role in maintaining lung homeostasis and the development of respiratory diseases. However, there have not been detailed characteristics of lung microbiome in health and respiratory diseases. Bronchoalveolar lavage fluid of 43 healthy individuals, 23 COVID patients, and 28 non-small cell lung cancer patients was conducted to characterize microbial diversity and function by metagenomic sequencing. We identified 196 species in health lung after removing low abnudance species. The most abundant species were Staphylococcus aureus, Salmonella enterica, and Klebsiella pneumoniae. Keystone species were identified through co-network analysis, such as Granulicatella adiacens and Mogibacterium diversum. To further explore the microbial function in the healthy lung, we obtained 56 non-redundant metagenome-assembled genomes (MAGs) and subsequently classified them into nine phyla. Metabolism and genetic information processing exhibit high abundance, including bacterial secretion systems, protein export, and Staphylococcus aureus infection, indicating a close correlation between microbiota and the host. Furthermore, the microbiome pairwise distances of non-small cell lung cancer (NSCLC) participants were more similar to those of the healthy group than those of individuals with COVID-19. Rothia dentocariosa, Corynebacterium kefirresidentii, Sphingobium yanoikuyae were enriched in the healthy group, while Schaalia odontolytica, Actinomyces graevenitzii, and Rothia mucilaginosa was enriched in the NSCLC group. Overall, this study provides a comprehensive overview of the diversity and gene function of the lung microbiome, which will facilitate future studies of microbiota associated with respiratory diseases in humans.

microbiology↗