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Yang, Z.

Publications and source records attributed to Yang, Z..

At least 307 records · Page 17Linked to original sources

Scaling laws of molecular residence time

Understanding the molecular residence autocorrelation function in liquid is of fundamental importance in physical and life science. Encoded in this function is not only the binding properties, but also the information of the liquid environment. Based on extensive in silico experiments and theoretical analysis, we reveal that power law residence scaling arises in both passive and active liquid, in contrast to the common sense of exponential decay. In simple homogeneous liquid, the scaling exponent depends solely on the system dimensionality. Such scaling law is robust against the superposition of diverse binding energies in single-phase liquid but can be breached if the system undergoes phase separation. Remarkably, in a dissipative system where phase separation is subject to non-equilibrium feedback controls, an anomalous power law emerges whose scaling exponent is in line with the puzzling residence scaling of transcription factors reported in recent experiments. Our results highlight the sensitivity of molecular residence to its surrounding liquid and suggest that active phase separation can serve as a scaling proofreading mechanism in gene regulation.

biophysics↗

Gentle rhodamines for live-cell fluorescence microscopy

Rhodamines have been continuously optimized in brightness, biocompatibility, and colors to fulfill the demands of modern bioimaging. However, the problem of phototoxicity caused by the excited fluorophore under long-term illumination has been largely neglected, hampering their use in time-lapse imaging. Here we introduce cyclooctatetraene (COT) conjugated rhodamines that span the visible spectrum and exhibit significantly reduced phototoxicity. We identified a general strategy for the generation of Gentle Rhodamines, which preserved their outstanding spectroscopic properties and cell permeability while showing an efficient reduction of singlet-oxygen formation and diminished cellular photodamage. Paradoxically, their photobleaching kinetics do not go hand in hand with reduced phototoxicity. By combining COT-conjugated spirocyclization motifs with targeting moieties, these gentle rhodamines compose a toolkit for time-lapse imaging of mitochondria, DNA, and actin and synergize with covalent and exchangeable HaloTag labeling of cellular proteins with less photodamage than their commonly used precursors. Taken together, the Gentle Rhodamines generally offer alleviated phototoxicity and allow advanced video recording applications, including voltage imaging.

cell biology↗

A single-cell 3D spatiotemporal multi-omics atlas from Drosophila embryogenesis to metamorphosis

The development of a multicellular organism is a highly intricate process tightly regulated by numerous genes and pathways in both spatial and temporal manners. Here, we present Flysta3D, a comprehensive multi-omics atlas of the model organism Drosophila, spanning its developmental lifespan from embryo to pupa. Our datasets encompass 3D single-cell spatial transcriptomic, single-cell transcriptomic, and single-cell chromatin accessibility information. By integrating these multi-dimensional data, we constructed cell state trajectories that uncover the detailed profiles of tissue development. With a focus on the central nervous system (CNS) and midgut, we dissected the spatiotemporal dynamics of gene regulatory networks, cell type diversity, and morphological changes from a multi-omics perspective. This extensive atlas provides an unprecedentedly rich resource and serves as a systematic platform for studying Drosophila development with integrated single-cell data at an ultra-high spatiotemporal resolution.

developmental biology↗

OsNF-YB7 inactivates OsGLK1 to inhibit chlorophyll biosynthesis in rice embryo

As a master regulator of seed development, Leafy Cotyledon 1 (LEC1) promotes chlorophyll (Chl) biosynthesis in Arabidopsis, but the mechanism underlying this remains poorly understood. Here, we found that loss of function of OsNF-YB7, a LEC1 homolog of rice, leads to chlorophyllous embryo, indicating that OsNF-YB7 plays an opposite role in Chl biosynthesis in rice compared with that in Arabidopsis. OsNF-YB7 regulates the expression of a group of genes responsible for Chl biosynthesis and photosynthesis by directly binding to their promoters. In addition, OsNF-YB7 interacts with Golden 2-Like 1 (OsGLK1) to inhibit the transactivation activity of OsGLK1, a key regulator of Chl biosynthesis. Moreover, OsNF-YB7 can directly repress OsGLK1 expression by recognizing its promoter in vivo, indicating the involvement of OsNF-YB7 in multiple regulatory layers of Chl biosynthesis in rice embryo. We propose that OsNF-YB7 functions as a transcriptional repressor to regulate Chl biosynthesis in rice embryo.

plant biology↗

SKSR1 identified as key virulence factor in Cryptosporidium by genetic crossing

Cryptosporidium parvum is a major cause of severe diarrhea. Although isolates of this zoonotic parasite exhibit significant differences in infectivity and virulence, the genetic determinants for these traits are not clear. In this study, we used classical genetics to cross two C. parvum isolates of different virulence and used bulked segregant analysis of whole-genome sequence data from the progeny to identify quantitative trait loci (QTL) associated with Cryptosporidium infectivity and virulence. Of the 26 genes in three QTL, two had loss-of-function mutations in the low-virulence isolates. Deletion of the SKSR1 gene or expression of the frame-shift mutant sequence reduced the pathogenicity of infection in vivo. SKSR1 is a polymorphic secretory protein expressed in small granules and secreted into the parasite-host interface. These results demonstrate that SKSR1 is an important virulence factor in Cryptosporidium, and suggest that this extended family may contribute to pathogenesis.

microbiology↗

Cell-autonomous and non-cell-autonomous effects of arginase-II on cardiac aging

Aging is a predominant risk factor for heart disease. Aging heart reveals low-grade chronic inflammation, cell apoptosis, cardiac fibrosis, and increased vulnerability to ischemic injury. The underlying molecular mechanisms responsible for the cardiac aging phenotype and its susceptibility to injury are far from being fully understood. Although previous literature reports a role of the mitochondrial enzyme arginase-II (Arg-II) in development of heart failure, contradictory results are reported and no systematic analysis of cellular expression and localization of Arg-II in the heart has been performed. Whether and how Arg-II participates in cardiac aging are still unknown. In this study, we demonstrate, to our surprise, that Arg-II is not expressed in cardiomyocytes from aged mice and human patients, but upregulated in non-myocytes of the aging heart, including macrophages, fibroblasts, endothelial cells. Mice with genetic deficiency of arg-ii (arg-ii-/-) are protected from age-associated cardiac inflammation, myocyte apoptosis, interstitial and perivascular fibrosis, endothelial-mesenchymal transition (EndMT), and susceptibility to ischemic injury. Further experiments show that Arg-II mediates IL-1{beta} release from macrophages of old mice, contributing to the above-described cardiac aging phenotype. In addition, Arg-II enhances mitochondrial reactive oxygen species (mtROS) and activates cardiac fibroblasts that is inhibited by inhibition of mtROS. Thus, our study demonstrates a non-cell-autonomous effect of Arg-II on cardiomyocytes, fibroblasts, and endothelial cells mediated by IL-1{beta} from aging macrophages as well as a cell-autonomous effect of Arg-II through mtROS in fibroblasts contributing to cardiac aging phenotype.

physiology↗

The Mechanism Insight into Bacterial Degradation of Pentachlorobiphenyl

Bacterial degradation mechanism for high chlorinated pentachlorobiphenyl (PentaCB) with worse biodegradability has not been fully elucidated, which could limit the full remediation of PCBs-combined pollution. In this research, using enzymatic screening method, a new PentaCB-degrading bacterium M. paraoxydans that has not been reported was obtained. The characteristic of its intracellular enzymes, proteome and metabolome variation during PentaCB degradation were investigated systematically. The results showed that PentaCB (PCB101, 1 mg/L) degradation rate could arrive 23.9% within 4 h till complete degradation within 12 h. The intracellular enzyme compound was optimally active at pH 6.0. The 12 up-regulated characterized proteins involved ABC transporter substrate-binding protein, translocase protein TatA and signal peptidase I (SPase I) indicated that functional proteins for PentaCB degradation were present both in the cytoplasm and outer surface of cytoplasmic membrane. There were also 5 differential metabolites strongly associated with above proteins in which the up-regulated 1, 2, 4-benzenetriol was enriched into the degradation pathways of benzoate, chlorocyclohexane, chlorobenzene and aminobenzoate. Bacterial degradation of PentaCB necessitates transmembrane transport, energy consumption, protein export, biofilm formation and quorum sensing. These findings hold significant theory and application value for PCBs biodegradation.

microbiology↗

Capsaicin acts as a novel NRF2 agonist to suppress ethanol induced gastric mucosa oxidative damage by directly disrupting the KEAP1-NRF2 interaction

Excessive alcohol consumption poses significant health risks and is closely associated with oxidative damage. The KEAP1-NRF2-ARE signaling pathway serves as the primary antioxidant system. However, current small molecule inhibitors are all covalently bound to KEAP1, meaning that once bound, they are not easily dissociated, while continuous inhibition of KEAP1 exhibits severe side effects. In this study, BLI, CETSA, Pull-down, Co-IP and HDX-MS assay analysis were conducted to detect the KEAP1 binding behavior of natural product, capsaicin (CAP), both in vitro and in cells. The ethanol-induced acute gastric mucosal damage rat model was also established to evaluate the therapeutic effect of CAP. Our findings demonstrated that CAP mitigated mitochondrial damage, facilitated the nuclear translocation of NRF2, leading to the up-regulation of downstream antioxidant response elements, HMOX1, TXN, GSS and NQO1 in GES-1 cells. Furthermore, CAP directly bind to KEAP1 and inhibit the interaction between KEAP1 and NRF2. In the KEAP1-knockout 293T cells, CAP failed to activate NRF2 expression. We identified that CAP non-covalently bound to Kelch domain and allosterically regulated three specific regions of KEAP1 : L342-L355, D394-G423 and N482-N495. To improve drug solubility and delivery efficiency, we developed IR-Dye800 modified albumin coated CAP nanoparticles. The nanoparticles significantly reduced the gastric mucosal inflammation and activated NRF2 downstream genes in vivo. Our hypothesis was further verified our hypothesis in Nfe2l2-knockout mice. This study provides new insights that CAP is a safe and novel NRF2 agonist by allosterically regulating KEAP1, which may contribute to the development of lead drugs for oxidative stress-related illness, e.g. aging, cancer, neurodegenerative and cardiovascular diseases.

cell biology↗

Single-cell RNA-seq analysis profiling characterizes differences in cell composition and physiology between normal tissue, treatment-naive, and cisplatin-treated ovarian cancer

BackgroundIntense efforts have focused on identifying heterogeneity of the cellular composition in ovarian cancer. However, tissue composition and physiological conditions of cancer cells in cisplatin-sensitive ovarian cancer remains largely unknown. Moreover, comparisons of different cellular states in normal tissue, in treatment naive ovarian cancer, and in cisplatin-treated tissue after adjuvant therapy of cisplatin-sensitive ovarian cancer at the single-cell level might offer clues for ovarian cancer treatment and prevention of cisplatin-resistance formation. MethodsSingle-cell transcriptome sequencing of a cisplatin-treated ovarian cancer was performed. Data sets of non-tumorous ovarian tissues and treatment-naive ovarian cancer were downloaded from the European Genome-phenome Archive (accession number EGAS00001004987). Quality control, batch effect correction, integration, and clustering analysis of the integrated single-cell transcriptome data was done. Cell subsets were annotated based on surface marker phenotypes. Finally, the proportions of subclusters, the immune cell population, and the potential biological processes among different cellular states were compared. ResultsSixteen distinct cell subsets were identified from the integrated single-cell transcriptome sequencing data of a pool of all tissues. The composition of the three different tissue types was characterized. The proportion of fibroblasts in cisplatin-treated ovarian tumor was remarkably lower than in treatment-naive ovarian tumor (1.33% vs. 13.53%, p < 0.05). Moreover, each subjects sample had differing relative proportions of the identified cell types. In primary untreated ovarian cancer, the prevalent immune cells were B cells and myeloid-related immunosuppressive M2 macrophages. However, there were less B cells and myeloid-related immunosuppressive M2 macrophages after cisplatin-treatment, while significantly more T cells were found. The physiological cellular state in primary untreated ovarian tumors was associated with dysfunctional gene expression and modulation of cellular homeostasis, while cells from cisplatin-treated tumor showed more activation of immune and inflammatory genes as compared to healthy ovarian tissue. ConclusionOur molecular gene expression analysis allowed for the separation and identification of differences in normal ovarian tissues, treatment-naive, and cisplatin-sensitive ovarian cancer cell populations at single-cell resolution. We identified different cell type composition and discriminative marker expression concerning specific cell subsets and identified differences among their physiological cell states. This knowledge may open new possibilities for elucidating important pathogenetic features and therapeutic strategies for treating ovarian cancer.

cancer biology↗

Integrated Analyses of Multi-omic Data Derived from Paired Primary Lung Cancer and Brain Metastasis Reveals the Metabolic Vulnerability as a Novel Therapeutic Target

Lung cancer brain metastases (LC-BrMs) are frequently associated with dismal mortality rates in patients with lung cancer; however, standard of care therapies for LC-BrMs are still limited in their efficacy. A deep understanding of molecular mechanisms and tumor microenvironment of LC-BrMs will provide us with new insights into developing novel therapeutics for treating patients with LC-BrMs. Here, we performed integrated analyses of genomic, transcriptomic, proteomic and metabolomic data which were derived from a total number of 174 patients with paired and unpaired primary lung cancer and LC-BrM, spanning four published and two newly generated patient cohorts on both bulk and single cell levels. We uncovered that LC-BrMs exhibited significantly higher intra-tumor heterogeneity. We also observed that mutations in a subset of genes were almost always shared by both primary lung cancers and LC-BrM lesions, including TTN, TP53, MUC16, LRP1B, RYR2, and EGFR. In addition, the genome-wide landscape of somatic copy number alterations was similar between primary lung cancers and LC-BrM lesions. Nevertheless, several regions of focal amplification were significantly enriched in LC-BrMs, including 5p15.33 and 20q13.33. Intriguingly, integrated analyses of transcriptomic, proteomic and metabolomic data revealed mitochondrial-specific metabolism was activated but tumor immune microenvironment was suppressed in LC-BrMs. Subsequently, we validated our results by conducting real-time quantitative reverse transcription PCR experiments, immunohistochemistry and multiplexed immunofluorescence staining of patients paired tumor specimens. Patients with a higher expression of mitochondrial metabolism genes but a lower expression of immune genes in their LC-BrM lesions tended to have a worse survival outcome. Therapeutically, targeting oxidative phosphorylation with gamitrinib in patient-derived organoids specific to LC-BrMs induced apoptosis and inhibited cell proliferation. The combination of gamitrinib plus anti-PD-1 immunotherapy significantly improved survival of mice bearing LC-BrMs. In conclusion, our findings not only provide comprehensive and integrated perspectives of molecular underpinnings of LC-BrMs but also contribute to the development of a potential, rationale-based combinatorial therapeutic strategy with the goal of translating it into clinical trials for patients with LC-BrMs.

cancer biology↗

ABCA7-dependent Neuropeptide-Y signalling is a resilience mechanism required for synaptic integrity in Alzheimer's disease

Alzheimers disease (AD) remains a complex challenge characterized by cognitive decline and memory loss. Genetic variations have emerged as crucial players in the etiology of AD, enabling hope for a better understanding of the disease mechanisms; yet the specific mechanism of action for those genetic variants remain uncertain. Animal models with reminiscent disease pathology could uncover previously uncharacterized roles of these genes. Using CRISPR/Cas9 gene editing, we generated a knockout model for abca7, orthologous to human ABCA7 - an established AD-risk gene. The abca7+/- zebrafish showed reduced astroglial proliferation, synaptic density, and microglial abundance in response to amyloid beta 42 (A{beta}42). Single-cell transcriptomics revealed abca7-dependent neuronal and glial cellular crosstalk through neuropeptide Y (NPY) signaling. The abca7 knockout reduced the expression of npy, bdnf and ngfra, which are required for synaptic integrity and astroglial proliferation. With clinical data in humans, we showed reduced NPY in AD correlates with elevated Braak stage, predicted regulatory interaction between NPY and BDNF, identified genetic variants in NPY associated with AD, found segregation of variants in ABCA7, BDNF and NGFR in AD families, and discovered epigenetic changes in the promoter regions of NPY, NGFR and BDNF in humans with specific single nucleotide polymorphisms in ABCA7. These results suggest that ABCA7-dependent NPY signaling is required for synaptic integrity, the impairment of which generates a risk factor for AD through compromised brain resilience. O_FIG O_LINKSMALLFIG WIDTH=197 HEIGHT=200 SRC="FIGDIR/small/573893v1_ufig1.gif" ALT="Figure 1"> View larger version (73K): org.highwire.dtl.DTLVardef@eecf7forg.highwire.dtl.DTLVardef@78d8e0org.highwire.dtl.DTLVardef@1e65d71org.highwire.dtl.DTLVardef@100db01_HPS_FORMAT_FIGEXP M_FIG Graphical abstract C_FIG

neuroscience↗

Homology detection using a protein secondary structure-based large language model

Detection of homology among proteins is fundamental to understanding protein function. Unfortunately, traditional homology searches using amino acid sequence similarity are limited when numerous amino acid substitutions have accumulated either due to billions of years of evolution or through processes of accelerated change. Recent applications of deep-learning approaches demonstrate that "protein language" models of amino acid sequences can improve the accuracy of the traditional homology searches. Ultimately, the ability to work seamlessly with tertiary structures of proteins will solve the homology detection challenge and provide accompanying insights directly related to function, but to date the use of 3D structures suffers both from data availability and computational bottlenecks. Herein, we present the Protein Secondary Structure Language (ProSSL) model, an efficient encoding of protein secondary structure information in a Transformer-based deep-learning architecture. We conjecture that the secondary protein structure, which is better conserved than primary sequences and much more easily predictable and available than tertiary protein structure, could aid in the task of homology detection. ProSSL has the computational advantages of primary sequence-based homology detection, while also providing important structural information for similarity scoring. Using two case studies of large, diverse viral protein families, we show that the ProSSL model successfully captures patterns of secondary structure arrangements and is effective in detecting homologs either as a pre-trained or fine-tuned model. In both tasks, we accurately detect members of these protein families, including those missed in traditional amino acid similarity searches. We also illustrate how functional insights from the individual ProSSL models could be obtained from the use of the Shapley Additive exPlanations (SHAP) values. Author SummaryWhen DNA is obtained from an organism or an environment, scientists are tasked with determining the functions of the proteins encoded in the genetic material. Such "functional annotation" relies on assigning functions based on the similarity of the proteins to counterparts in databases comprising annotated sequence data. Especially challenging is an ability to recognize similarity in proteins that accumulated a lot of amino acid changes. It is well-known that spatial structure of proteins that share ancestry and perform similar functions evolves much slower than the sequences of the proteins amino acids. Thus, comparison of 3D structures could address this challenge, but the data is still limited to certain classes of proteins, and the requisite computations are expensive. Herein we present a deep-learning model derived from protein secondary structure representation, a symbolic encoding of the way neighboring amino acid residues of a protein interact with each other. Unlike 3D structure, the secondary structure is quickly and accurately predictable from amino acid sequences of proteins. Using two viral proteins as case studies, we demonstrate that our model works well for detection of protein similarity, including identification of very distantly related proteins.

bioinformatics↗

The activated plant NRC4 immune receptor forms a hexameric resistosome

Innate immune responses against microbial pathogens in both plants and animals are regulated by intracellular receptors known as Nucleotide-binding Leucine-rich Repeats (NLR) proteins. In plants, these NLRs play a crucial role in recognizing pathogen effectors, thereby initiating the activation of immune defense mechanisms. Notably, certain NLRs serve as "helper" NLR immune receptors (hNLR), working in tandem with "sensor" NLR immune receptors (sNLR) counterparts to orchestrate downstream signaling events to express disease resistance. In this study, we reconstituted and determined the cryo-EM structure of the hNLR required for cell death 4 (NRC4) resistosome. The auto-active NRC4 formed a previously unanticipated hexameric configuration, triggering immune responses associated with Ca2+ influx into the cytosol. Furthermore, we uncovered a dodecameric state of NRC4, where the coil-coil (CC) domain is embedded within the complex, suggesting an inactive state, and expanding our understanding of the regulation of plant immune responses. One Sentence SummaryThe hexameric NRC4 resistosome mediates cell death associated with cytosolic Ca2+ influx.

plant biology↗

Camel milk affects serum metabolites by modulating the intestinal microflora

Gut microbes play a vital role in human health and are influenced by numerous factors including diet, genetics, and environment. (Fermented) Camel milk, which is abundant in nutrients and lacks allergenic proteins, has been consumed for its edible and medicinal properties for centuries. Research on camel milks impact on gut microbiota and host metabolism is still limited. The results found that sour camel milk contained various beneficial bacteria such as Lactobacillus helveticus, Acinetobacter lwoffii, Eubacterium coprostanoligenes group, Lachnospiraceae, which could be transported to the recipients intestines by diet. This study specified that the transportation of microbiome happened both intra- and inter-species and played a principal role in the formation of progeny gut microflora. An investigation on type 2 diabetic rats revealed that the composition of gut microflora and serum metabolites of those fed with high-dose camel whey was closer to that of the normal. Eubacterium limnetica, which can reduce the risk of diseases by producing MtcB protein, was found in the gut microflora of the ones taking camel milk. These results evidenced the high potential of camel milk as a functional food.

microbiology↗

Functional Connectivity, Tissue Microstructure And T2 At 11.1 Tesla Distinguishes Neuroadaptive Differences In Two Contusive Brain Injury Models In Rats

Traumatic brain injuries (TBIs), particularly contusive types, are associated with disruptions in neuronal communication due to focal and diffuse axonal injury, as well as alterations in the neuronal chemical environment. These changes can negatively impact neuronal networks beyond the primary injury site. In this Translational Outcomes Project in NeuroTrauma (TOP-NT) UG3 phase study, we sought to use multimodal neuroimaging biomarker approach to assess functional connectivity and brain tissue microstructure, along with T2 relaxometry, in two experimental rat models of TBI: controlled cortical impact (CCI) and lateral fluid percussive injury (LFPI). Rats underwent imaging using an 11.1 Tesla scanner at 2 and 30 days post-injury. Naive controls were scanned once to establish baseline comparisons for both TBI groups. Imaging modalities included functional magnetic resonance imaging (fMRI), diffusion-weighted imaging (DWI), and multi-echo T2 imaging. fMRI data were analyzed to evaluate functional connectivity across lateral and medial regions of interest (ROIs) in the cortical mantle, hippocampus, and dorsal striatum. DWI scans were used to generate maps of fractional anisotropy (FA) and mean, axial, and radial diffusivities (MD, AD, RD), focusing on cortical and white matter (WM) regions near the injury epicenter. Our findings revealed significantly increased contralateral intra-cortical connectivity at 2 days post-injury in both CCI and LFPI models, localized to similar cortical areas. This increased connectivity persisted at day 30 in the CCI model but not in LFPI. Changes in WM and cortical FA and diffusivities were observed in both models, with WM alterations predominating in CCI and cortical changes being more pronounced in LFPI. These results highlight the utility of multimodal MR imaging for characterizing distinct injury mechanisms in contusive and skull-penetrating TBI models.

neuroscience↗

Characterization of cortical neurodevelopment in vitro using gene expression and morphology profiles from single cells

AbstractDifferentiation of induced pluripotent stem cells (iPSC) towards neuronal lineages has enabled diverse cellular models of human neurodevelopment and related disorders. However, in vitro differentiation is a variable process that frequently leads to heterogeneous cell populations that may confound disease-relevant phenotypes. Here, we report a thorough characterization of cortical neuron differentiation from iPSCs using joint profiling of neuronal morphology and transcriptomics in single cells. We assayed 60,000 developing neurons across three timepoints with CellPainting, a high-content imaging method, and single-cell RNA-sequencing (scRNA-seq). By modeling the relationship between morphological features and gene expression within our differentiation system, we annotated image-based features with biological functions and found that while phenotypes related to cell morphology capture broader neuronal classes than scRNA-seq, they enhance our ability to quantify the biological processes that drive neuronal differentiation over time, such as mitochondrial function and cell cycle. Further, we found that while over 60% of the cells match those seen in the fetal brain, 28% represented metabolically abnormal cell states and broader neuronal classes specific to in vitro cells. Finally, we show that specific subtypes of iPSC-derived cortical neurons are a relevant model for a range of brain-related complex traits, including schizophrenia and bipolar disorder, highlighting the potential of multi-modal single cell phenotyping for disease modeling.

genomics↗

Long-term abstinence reduces optimal energy required for transitions from the exogenous networks to the frontoparietal network in methamphetamine addicts

Methamphetamine (MA) use disorder is a chronic neurotoxic brain disease characterized by a high risk of relapse driven by intense cravings. However, the neurobiological signatures of cravings remain unclear, limiting the effectiveness of various treatment methods. Diffusion MRI (dMRI) scans from 62 MA users and 57 healthy controls (HC) were used in this study. The MA users were longitudinally followed up during their period of long-term abstinence (duration of long-term abstinence: 347.52{+/-}99.25 days). We systematically quantified the control ability of each brain region for craving-associated state transitions using network control theory from a causal perspective. Craving-associated structural alterations (CSA) were investigated through multivariate group comparisons and biological relevance analysis. The neural mechanisms underlying CSA were elucidated using transcriptomic and neurochemical analyses. We observed that long-term abstinence-induced structural alterations significantly influenced the state transition energy involved in the cognitive control response to external information, which correlated with changes in craving scores (r [~] 0.35, P <0.01). Our causal network analysis further supported the crucial role of the prefrontal cortex (PFC) in craving mechanisms. Notably, while the PFC is central to the craving, the CSAs were distributed widely across multiple brain regions (PFDR<0.05), with strong alterations in somatomotor regions (PFDR<0.05) and moderate alterations in high-level association networks (PFDR<0.05). Additionally, transcriptomic, chemical compounds, cell-type analyses, and molecular imaging collectively highlight the influence of neuro-immune communication on human craving modulation. Our results offer an integrative, multi-scale perspective on unraveling the neural underpinnings of craving and suggest that neuro-immune signaling may be a promising target for future human addiction therapeutics.

neuroscience↗

Armillaria korhonenii, the sixteenth biological species of Armillaria from China

Armillaria korhonenii, designated as Chinese biological species Q (CBSQ) here, is described as a new species based on phylogenetic and morphological evidence as well as the results of mating tests. This species is the sixteenth biological species of Armillaria reported from China following the discovery of 15 previously known biological species. Phylogenetically, A. korhonenii is the earliest divergent lineage of the genus Armillaria as inferred from the nucleotide sequences of the Elongation Factor 1-Alpha (EF1a). Morphologically, it is characterized by its ellipsoid to elongate basidiospores, yellowish orange to honey yellow pileus with fibrillose squamules. Mating tests indicated that A. korhonenii is a tetrapolar heterogeneous species and is inter-sterile with all the tested species except partial compatibility with CBSH.

microbiology↗