Biology subjects

Xu, X.

Publications and source records attributed to Xu, X..

At least 541 records · Page 30Linked to original sources

bioRxiv2021

Microinductor-Fused Atomic Force Microscopy Cantilevers for Dynamic Imaging and Multimodal Manipulation

Recent advances in atomic force microscopy (AFM) imaging and force spectroscopy have demonstrated improvements in rapid acquisition of quantitative data for applications in materials science, surface characterization, and biology. However, conventional AFM technology is limited in detection sensitivity and the ability to excite at off-resonance frequencies restricting broad utility of the technology. Here we demonstrate new AFM cantilevers fabricated with a planar microcoil at the tip region, which can be used to generate or sense highly-localized magnetic fields. Torsion/bending actuation of the cantilevers is accomplished with simple experimental configurations, enabling quantitative and simultaneous mapping of both stiffness and friction at the sample surface with more than one order of magnitude improvement in compositional contrast. Our method is compatible with commercial AFM systems, allowing us to clearly resolve small stiffness and friction variations in copolymer and biological samples that were difficult to detect by conventional AFM methods. In combination with fluorescence microscopy, we also generated localized fields to selectively stimulate and monitor structural changes in viable cells with nm-scale detail. Hybrid AFM cantilevers may be useful to characterize a broad range of complex material surfaces, in addition to combined physical and chemical analyses of single cells and biological microenvironments.

biophysics↗

bioRxiv2021

A novel cholinergic neural pathway and its role in the drug relapse

The lateral parabrachial nucleus (LPB) is critical hub implicated in the control of food intake, reward and aversion. Here, we identified a novel cholinergic projection from choline acetyltransferase (ChAT)-positive neurons in external portion of the lateral parabrachial nucleus (eLPBChAT) to {gamma}-aminobutyric acid (GABA) neurons in central nucleus of amygdala (CeAGABA), activation of which could block methamphetamine (METH)-primed conditioned place preference (CPP) in mice.

neuroscience↗

bioRxiv2021

Reduced virulence and enhanced host adaption during antibiotics therapy: A story of a within-host carbapenem-resistant Klebsiella pneumoniae sequence type 11 evolution in a fatal scrotal abscess patient

Carbapenem-resistant Klebsiella pneumoniae (CRKP) has disseminated globally and become a major threat to human life. The sequence type (ST) 11 CRKP is a dominant clone in Asia, especially China, but how this clone evolves in vivo, then adapts to host and facilitates dissemination remain largely unknown. We analyzed the genomic dynamics of 4 ST11-CRKP isolates sequencially isolated from the urine of a patient with initial fatal scrotal abscess and finally recovered without effective medication. Genomic differences were identified and their implications for pathogenesis and host adaptation were investigated. The related transcriptional pathways were further explored by RNA-Seq. Genomic analysis identified 4-24 mutations and 94%-100% were synonymous or intergenic. The mutation rate of ST11-CRKP was 2.1x10-6-1.7x10-5 substitutions/site/year over 47 days of antibiotics therapy. During this period, CRKP underwent several adaptive changes including tigecycline resistance and virulence attenuation. Tigecycline resistance was caused by ramR ribosomal binding site (RBS) deletion, which has been described by us previously. In this study, we demonstrated that mutations associated with acyltransferase (act) and ompK26 caused the virulence attenuation of ST11-CRKP. act deletion reduced the production of capsular polysaccharide and enhanced biofilm formation. RNA-Seq analysis revealed that act influenced the expression of ldhA, bglX, mtnK and metE which likely participate in capsular synthesis and biofilm formation. ompK26 affected the virulence by its overexpression caused by the deletion of upstream repressor binding site. Our finding suggested that the broad genomic diversity, high evolutionary capacity and rapid within-host adaptability of ST11-CRKP might contribute to the worldwide dissemination of this clone. IMPORTANCECarbapenem-resistant Klebsiella pneumoniae (CRKP) has disseminated worldwide and can cause life threatening infections, including pneumonia, bloodstream infections, urinary tract infections, intra-abdominal infection, liver abscess and meningitis. CRKP infection is the leading cause of high mortality in clinical. The sequence type (ST) 11 CRKP is a dominant clone and accounts for 60% of CRKP infections in China. Recently, the ST11-CRKP with high transmissibility are increasingly identified. Understanding how this clone evolved is crucial in controlling its further dissemination. The significance of our research is identifying the in vivo genomic dynamics of ST11-CRKP and the genetic basis for ST11-CRKP to facilitate persistence and dissemination, which will has broader biomedical impacts on understanding of ST11-CRKP dissemination. Furthermore, our study also highlights the importance of monitoring the development of variation in antibiotics susceptibility and virulence of bacteria in clinical practice, considering that pathogens can rapidly adapt to host during the treatment.

microbiology↗

bioRxiv2021

iPSC modeling shows uncompensated mitochondrial mediated oxidative stress underlies early heart failure in hypoplastic left heart syndrome

Hypoplastic left heart syndrome (HLHS) is a severe congenital heart defect with 30% mortality from heart failure (HF) in the first year of life, but why only some patients suffer early-HF and its cause remain unknown. Modeling using induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) showed early-HF patient iPSC-CM have increased apoptosis, redox stress, and failed antioxidant response. This was associated with mitochondrial permeability transition pore (mPTP) opening, mitochondrial hyperfusion and respiration defects. Whereas iPSC-CM from patients without early-HF had hyper-elevated antioxidant response with increased mitochondrial fission and mitophagy. Single cell transcriptomics showed dichotomization by HF outcome, with mitochondrial dysfunction and endoplasmic reticulum (ER) stress associated with early-HF. Importantly, oxidative stress and apoptosis associated with early HF were rescued by sildenafil inhibition of mPTP opening or TUDCA suppression of ER stress. Together these findings demonstrate a new paradigm for modeling clinical outcome in iPSC-CM, demonstrating uncompensated mitochondrial oxidative stress underlies early HF in HLHS.

cell biology↗

bioRxiv2021

Mesenchymal stem cell subpopulations and their heterogeneity of response to inductions revealed by single-cell RNA-seq

Mesenchymal stem/stromal cells (MSCs) are promising cell source for regenerative medicine and treatment of autoimmune disorders. Comparing MSCs from different tissues at single cell level is fundamental for optimizing clinical applications. Here we analyzed single cell RNA-seq data of MSCs from 4 tissues, namely umbilical cord, bone marrow, synovial tissue and adipose tissue. We identified 3 major cell subpopulations, namely osteo-MSCs, chondro-MSCs, adipo/myo-MSCs, across all MSC samples. MSCs from umbilical cord exhibited the highest immunosuppression, potentially indicating it is the best immune modulator for autoimmune diseases. The differentiation potentials of MSC subpopulations, which are strongly associated with their subtypes and tissue sources, showed pronounced subpopulation differences. We found MSC subpopulations expanded and differentiated when their subtypes consist with induction directions, while the other subpopulations shrank. We identified the genes and transcription factors underlying each induction at single cell level and subpopulation level, providing better targets for improving induction efficiency.

genetics↗

bioRxiv2021

Metagenome-genome-wide association studies reveal human genetic impact on the oral microbiome

The oral microbiota contains billions of microbial cells, which could contribute to diseases in a number of body sites. Challenged by eating, drinking and dental hygiene on a daily basis, the oral microbiota is regarded as highly dynamic. Here, we report significant human genomic associations with the oral metagenome from more than 1,915 individuals, for both the tongue dorsum and saliva. We identified five genetic loci associated with oral microbiota at study-wide significance (p < 3.16 x 10-11). Four of the five associations were well replicated in an independent cohort of 1,439 individuals: rs1196764 at APPL2 with Prevotella jejuni, Oribacterium uSGB 3339 and Solobacterium uSGB 315; rs3775944 at the serum uric acid transporter SLC2A9 with Oribacterium uSGB 1215, Oribacterium uSGB 489 and Lachnoanaerobaculum umeaense; rs4911713 near OR11H1 with species F0422 uSGB 392; and rs36186689 at LOC105371703 with Eggerthia. Further analyses confirmed 84% (386/455 for tongue dorsum) and 85% (391/466 for saliva) of genetic-microbiota associations including 6 genome-wide significant associations mutually validated between the two niches. Human genetics accounted for at least 10% of oral microbiome compositions between individuals. Machine learning models showed that polygenetic risk score dominated over oral microbiome in predicting predisposing risk of dental diseases such as dental calculus and gingival bleeding. These findings indicate that human genetic differences are one explanation for a stable or recurrent oral microbiome in each individual.

genetics↗

bioRxiv2021

Structures of the human cholecystokinin 1 (CCK1) receptor bound to Gs and Gq mimetic proteins: insight into mechanisms of G protein selectivity

G protein-coupled receptors (GPCRs) are critical regulators of cellular function acting via heterotrimeric G proteins as their primary transducers with individual GPCRs capable of pleiotropic coupling to multiple G proteins. Structural features governing G protein selectivity and promiscuity are currently unclear. Here we used cryo-electron microscopy to determine structures of the CCK1R bound to the CCK peptide agonist, CCK-8 and two distinct transducer proteins, its primary transducer Gq, and the more weakly coupled Gs. As seen with other Gq/11-GPCR complexes, the Gq-5 helix bound to a relatively narrow pocket in the CCK1R core. Surprisingly, the backbone of the CCK1R and volume of the G protein binding pocket was essentially equivalent when Gs was bound, with the Gs 5 helix displaying a conformation that arises from "unwinding" of the far C-terminal residues, compared to canonically Gs coupled receptors. Thus, integrated changes in the conformations of both the receptor and G protein play critical roles in the promiscuous coupling of individual GPCRs. One-Sentence SummaryCryo-EM structures of the CCK-1R reveal key mechanisms for promiscuous G protein coupling.

pharmacology and toxicology↗

bioRxiv2021

Digital 3D Brain MRI Arterial Territories Atlas

The locus and extent of brain damage in the event of vascular insult can be quantitatively established quickly and easily with vascular atlases. Although highly anticipated by clinicians and clinical researchers, no digital MRI arterial atlas is readily available for automated data analyses. We created a digital arterial territory atlas based on lesion distributions in 1,298 patients with acute stroke. The lesions were manually traced in the diffusion-weighted MRIs, binary stroke masks were mapped to a common space, probability maps of lesions were generated and the boundaries for each arterial territory was defined based on the ratio between probabilistic maps. The atlas contains the definition of four major supra- and infra-tentorial arterial territories: Anterior, Middle, Posterior Cerebral Arteries and Vertebro-Basilar, and sub-territories (thalamoperforating, lenticulostriate, basilar and cerebellar arterial territories), in two hierarchical levels. This study provides the first publicly-available, digital, 3D deformable atlas of arterial brain territories, which may serve as a valuable resource for large-scale, reproducible processing and analysis of brain MRIs of patients with stroke and other conditions.

neuroscience↗

bioRxiv2021

Inactivation of the Hippo Tumor Suppressor Pathway Promotes Melanoma

Human melanomas are commonly driven by activating mutations in BRAF, which promote melanocyte proliferation through constitutive stimulation of the MAPK pathway. However, oncogenic BRAF alone is insufficient to promote melanoma; instead, its expression merely induces a transient burst of proliferation that ultimately ceases with the development of benign nevi (i.e. moles) comprised of growth-arrested melanocytes. The tumor suppressive mechanisms that induce this melanocytic growth arrest remain poorly understood. Recent modeling studies have suggested that the growth arrest of nevus melanocytes is not solely due to oncogene activation in individual cells, but rather due to cells sensing and responding to their collective overgrowth, similar to what occurs in normal tissues. This cell growth arrest is reminiscent of the arrest induced by activation of the Hippo tumor suppressor pathway, which is an evolutionarily conserved pathway known to regulate organ size. Herein, we demonstrate that oncogenic BRAF signaling activates the Hippo pathway in vitro, which leads to inhibition of the pro-growth transcriptional co-activators YAP and TAZ, ultimately promoting the growth arrest of melanocytes. We also provide evidence that the Hippo tumor suppressor pathway is activated in growth-arrested nevus melanocytes in vivo, both from single-cell sequencing of mouse models of nevogenesis and human tissue samples. Mechanistically, we observe that oncogenic BRAF promotes both ERK-dependent alterations in the actin cytoskeleton and whole-genome-doubling events, and that these two effects independently promote Hippo pathway activation. Lastly, we demonstrate that abrogation of the Hippo pathway, via melanocyte-specific deletion of the Hippo kinases Lats1/2, enables oncogenic BRAF-expressing melanocytes to bypass nevus formation, thus leading to the rapid onset of melanoma with 100% penetrance. This model is clinically relevant, as co-heterozygous loss of LATS1/2 is observed in [~]15% of human melanomas. Collectively, our data reveal that the Hippo pathway enforces the stable growth arrest of nevus melanocytes and therefore represents a critical and previously unappreciated barrier to melanoma development.

cancer biology↗

bioRxiv2021

Ground tissue circuitry regulates organ complexity in cereal roots

Most plant roots have multiple cortex layers that make up the bulk of the organ and play key roles in physiology, such as flood tolerance and symbiosis. However, little is known about the formation of cortical layers outside of the highly reduced anatomy of the model Arabidopsis. Here we use single-cell RNAseq to rapidly generate a cell resolution map of the maize root, revealing an alternative configuration of the tissue formative SHORT-ROOT (SHR) signaling pathway adjacent to an expanded cortex. We show that maize SHR protein is hypermobile, moving at least eight cell layers into the cortex. Higher-order SHR mutants in both maize and Setaria have reduced numbers of cortical layers, showing that the SHR pathway controls expansion of cortical tissue in grasses that sets up anatomical complexity and a host of key traits. One sentence summarySingle-cell RNA-seq maps the maize root transcriptome uncovering a mechanism that regulates cortex layer number.

genomics↗

bioRxiv2021

Population genomics of Salmonella enterica serovar Weltevreden ST365, an emerging predominant causative agent of diarrheal disease

Salmonella enterica serovar Weltevreden is a recently emerged pathogen, and as such we lack a comprehensive knowledge of its microbiology, genomics, epidemiology and biogeography. In this study, we analyzed 174 novel S. Weltevreden isolates including 111 isolates recovered from diarrheal patients in China between 2006 and 2017. Our results demonstrate that the ST365 clone was the predominant causative agent of the diarrhea-outbreak during this period, as vast majority of the isolates recovered from diarrheal patients belonged to this sequence type (97.37%, 74/76). We also determined the ST365 clone as the predominant sequence type of S. Weltevreden from diarrheal patients globally from previously published sequences (97.51%, 196/201). In order to determine the possible antimicrobial genes and virulence factors associated with S. Weltevreden, we performed whole genome sequencing on our novel isolates. We were able to identify a range of key virulence factors associated with S. Weltevreden that are likely to be beneficial to their fitness and pathogenesis. Furthermore, we were able to isolate a novel 100.03-kb IncFII(S) type virulence plasmid that used the same replicon as pSPCV virulence plasmid. Importantly, we demonstrated through plasmid elimination a functional role for this plasmid in bacterial virulence. These findings are critical to further our knowledge of this high consequence pathogen. ImportanceSalmonella Weltevreden is a newly emerged foodborne pathogen and has caused several outbreaks of diarrheal diseases in some regions in the world. However, comprehensive knowledge of microbiology, genomics, epidemiology and biogeography of this newly emerged pathogen is still lack. In this study, we made an unexpected discovery that S. Weltevreden sequence type (ST) 365 is the causative agent in the diarrhea-outbreak in China and many other regions of the world. We also shown that this sequence type was widely recovered from animal, food, and environmental samples collected in different regions in the world. Importantly, we discovered a novel IncFII(S) type virulence plasmid commonly carried by S. Weltevreden strains of both human, animal, and food origins. These data facilitate future studies investigating the emergence of S. Weltevreden involved in diarrheal outbreaks and the global spread of S. Weltevreden strains.

microbiology↗

bioRxiv2021

Elevated CO2 reduces a common soybean leaf endophyte

Free-air CO2 enrichment (FACE) experiments have elucidated how climate change affects plant physiology and production. However, we lack a predictive understanding of how climate change alters interactions between plants and endophytes, critical microbial mediators of plant physiology and ecology. We leveraged the SoyFACE facility to examine how elevated [CO2] affected soybean (Glycine max) leaf endophyte communities in the field. Endophyte community composition changed under elevated [CO2], including a decrease in the abundance of a common endophyte, Methylobacterium sp. Moreover, Methylobacterium abundance was negatively correlated with co-occurring fungal endophytes. We then assessed how Methylobacterium affected the growth of co-occurring endophytic fungi in vitro. Methylobacterium antagonized most co-occurring fungal endophytes in vitro, particularly when it was more established in culture before fungal introduction. Variation in fungal response to Methylobacterium within a single fungal operational taxonomic unit (OTU) was comparable to inter-OTU variation. Finally, fungi isolated from elevated vs. ambient [CO2] plots differed in colony growth and response to Methylobacterium, suggesting that increasing [CO2] may affect fungal traits and interactions within the microbiome. By combining in situ and in vitro studies, we show that elevated [CO2] decreases the abundance of a common bacterial endophyte that interacts strongly with co-occurring fungal endophytes. We suggest that endophyte responses to global climate change will have important but largely unexplored implications for both agricultural and natural systems.

ecology↗

bioRxiv2021

Maize RAMOSA3 accumulates in nuclear condensates enriched in RNA POLYMERASE II isoforms during the establishment of axillary meristem determinacy.

Brief AbstractMaize meristem determinacy is regulated by Trehalose-6-Phosphate Phosphatase (TPP) metabolic enzymes RAMOSA3 and TPP4. However, this function is independent of their enzymatic activity, suggesting they have an unpredicted, or moonlighting function. Using whole-mount double immunolabeling and imaging processing, we investigated the co-localization of RA3 nuclear speckles with markers for transcription, chromatin state and splicing. We find evidence for RA3 co-localization with RNA POL II, a transcription marker, and not with markers for promoter chromatin remodeling or mRNA processing, suggesting a function of nuclear RA3 in mediating a transcriptional response during meristem determinacy.

plant biology↗

bioRxiv2021

Auxin-responsive (phospho)proteome analysis reveals regulation of cell cycle and ethylene signaling during rice crown root development

The rice root system, which primarily consists of adventitious/crown roots (AR/CR) developed from the coleoptile base, is an excellent model system for studying shoot-to-root trans-differentiation process. We reveal global changes in protein and metabolite abundance, and protein phosphorylation in response to an auxin stimulus during CR development. Global proteome and metabolome analyses of developing crown root primordia (CRP) and emerged CRs uncovered that the biological processes associated with chromatin conformational change, gene expression, and cell cycle were translationally regulated by auxin signaling. Spatial gene expression pattern analysis of differentially abundant proteins disclosed their stage-specific dynamic expression pattern during CRP development. Further, our tempo-spatial gene expression and functional analyses revealed that auxin creates a regulatory feedback module during CRP development and activates ethylene biosynthesis exclusively during CRP initiation. Ethylene signaling promotes CR formation by repressing the cytokinin response regulator, OsRR2. Additionally, the (phospho)proteome analysis identified differential phosphorylation of the Cyclin-dependent kinase G-2 (OsCDKG;2), and cell wall proteins, in response to auxin signaling, suggesting that auxin-dependent phosphorylation may be required for cell cycle activation, and cell wall synthesis during root organogenesis. Thus, our study provides evidence for the translational and post-translational regulation during CRP trans-differentiation downstream of the auxin signaling pathway. HighlightGlobal (phospho)proteome and metabolic profiling of rice CRP and CRs uncover differential proteins and metabolites associated with gene expression, cell cycle, ethylene signaling and cell wall synthesis during CR development.

plant biology↗

bioRxiv2021

Rescue of aberrant huntingtin palmitoylation ameliorates mutant huntingtin-induced toxicity

Huntington disease (HD) is a neurodegenerative disorder caused by a CAG expansion in the HTT gene that codes for an elongated polyglutamine tract in the huntingtin (HTT) protein. HTT is subject to multiple post-translational modifications (PTMs) that regulate its cellular function. Mutating specific PTM sites within mutant HTT (mHTT) in HD mouse models can modulate disease phenotypes, highlighting the key role of HTT PTMs in the pathogenesis of HD. These findings have led to increased interest in developing small molecules to modulate HTT PTMs in order to decrease mHTT toxicity. However, the therapeutic efficacy of pharmacological modulation of HTT PTMs in preclinical HD models remains largely unknown. HTT is palmitoylated at cysteine 214 by the huntingtin-interacting protein 14 (HIP14 or ZDHHC17) and 14-like (HIP14L or ZDHHC13) acyltransferases. Here, we assessed if HTT palmitoylation should be regarded as a therapeutic target to treat HD by (1) investigating palmitoylation dysregulation in rodent and human HD model systems, (2) measuring the impact of mHTT-lowering therapy on brain palmitoylation, and (3) evaluating if HTT palmitoylation can be pharmacologically modulate. We show that palmitoylation of mHTT and some HIP14/HIP14L-substrates is decreased early in multiple HD mouse models, and that aging further reduces HTT palmitoylation. Lowering mHTT in the brain of YAC128 mice is not sufficient to rescue aberrant palmitoylation. However, we demonstrate that mHTT palmitoylation can be normalized in COS-7 cells, in YAC128 cortico-striatal primary neurons and HD patient-derived lymphoblasts using an acyl-protein thioesterase (APT) inhibitor. Moreover, we show that modulating palmitoylation reduces mHTT aggregation and mHTT-induced cytotoxicity in COS-7 cells and YAC128 neurons. HighlightsO_LIPalmitoylation of mHTT is reduced in multiple transgenic HD mouse models C_LIO_LIHTT palmitoylation decreases with increasing polyQ length in HD patient cells C_LIO_LImHTT-lowering in mouse brains does not rescue aberrant palmitoylation C_LIO_LImHTT palmitoylation in HD patient-derived cells can be rescued via APT inhibition C_LIO_LIPromoting palmitoylation reduces mHTT aggregation and cytotoxicity in vitro C_LI

neuroscience↗

bioRxiv2021

Single cell transcriptome analysis of decidua macrophages in normal and recurrent spontaneous abortion patients

Due to the heterogeneity and different polarization state of decidual macrophages (dM{Phi}), they play an important role during the pregnancy, but their definition and exact function remain elusive. We isolated CD14+CD45+ dM{Phi} from the normal or RSA decidua by flow cytometry, followed by single cell RNA sequencing (scRNA-seq). In total, 23,062 single-cell transcriptomes of macrophage were profiled (12,470 Normal and 10,592 RSA), which were divided into 13 major clusters via T-distributed stochastic neighbor embedding (t-SNE) visualization. We observed that there is higher percentage composition of M1 cells (70.6%) in the normal decidua, and higher percentage composition of M2 cells (68.3%) in the RSA decidua. We identified new markers (M1: S100A8, S100A9, M2: SELENOP, FOLR2, RNASE1) and secreted cytokines (M1: IL1{beta}, TNFSF13B and MMP9; M2: CCL3, CCL4) of the dM{Phi}. We found that cluster 10 as the specific cluster of dM{Phi} highly expressing BAG3 in normal group and cluster 7 specific highly expressing CXCL9/10/11 chemokine. After pseudo-time trajectory analysis, we found that the dM{Phi} formed a continuous "V-shaped" trajectory, with M1 and M2 type cells mainly occupying the two heads. We found that NF{kappa}B1, MYC and TCF12 acted as the key transcription factors of dM{Phi}. Our study redefined the polarization state and physiological characteristic of dM{Phi} in early normal and RSA pregnancy, which suggests a novel view and therapeutic target for spontaneous abortion prevention.

cell biology↗

bioRxiv2021

Broccoli sprout Sulforaphane affected hemodynamics and aorta myogenic spontaneous rhythmic contraction in sanitized water uptake mice

Drinking seawater erodes water source will lead to hemodynamic changes in cardiovascular system. The erosion affected vascular biomechanics further interrupt the blood supply in arterial network. In this study, we investigated the carotid arterial hemodynamics in salinity water fed mice, and the relative spontaneous contraction of aorta preparation. The biological effect of Broccoli sprout Sulforaphane was assessed in intake hemodynamic changes. Kunming mice were randomly divided into seawater feeding group, seawater + Sulforaphane group, freshwater feeding group, fresh water + Sulforaphane group. After 4 weeks of feeding, the pressure waveforms of common carotid artery were analyzed in vivo. The enhanced common carotid arterial pressures were calculated according to the breakpoint of systolic pressure rising phase. The ejection time was calculated according to the dicrotic notch. In vitro, the isolated aorta biomechanical features were tested on a micro stepping platform. The passive tension and relative myogenic spontaneous contraction were evaluated. The results indicated that in salinity water fed mice heart rate, ejection period were significantly accelerated. The systolic pressure breakpoint of the ascending phase was significantly increased; however, the central aortic pressure augment index was decreased. In vitro study, the isolated aorta preparations indicated remarkable myogenic spontaneous contraction in salinity water fed mice. The spontaneous contraction indicated a significant cycle pattern, the waveform cluster changes regularly in one cycle, maximal amplitude of myogenic autonomic contraction increased significantly. Spontaneous contraction became more active, however cycle duration shortened. In biological effect of Broccoli sprout supplement, Sulforaphane was effective in reducing the heart rate, prolonging ejection period, improving systolic pressure and pulse pressure amplitude in salinity water fed mice. We concluded that long-term salinity water uptake can form a new hypertension model in mice, which can affect the changes of carotid artery hemodynamics and local blood supply. The Broccoli sprout Sulforaphane can improve the high systolic blood pressure and ejection period of artery, and its mechanism needs further study.

physiology↗

bioRxiv2021

IL-10 driven memory T cell survival and Tfh differentiation promote HIV persistence

Mechanisms regulating HIV persistence are complex and not well understood. Increased IL-10 levels were positively associated with HIV reservoir in blood and lymph nodes (LN) of treated HIV aviremic individuals. In LNs, B cells, regulatory T cells, follicular T helper cells (Tfh), monocytes and macrophages contributed to the frequencies of IL10+ cells. Cells with HIV DNA in LNs were in close proximity to IL-10+ cells and/or had the active form of STAT3, the transcription downstream of IL-10. Gene signatures and proteins associated to cell survival, Co-inhibitory receptors expression, maintenance of memory T cells, immune metabolism and Tfh frequencies were all modulated by IL-10 and associated with HIV reservoir persistence. In vitro, STAT3 knockout or neutralization of IL-10, reverted all the aforementioned pathways and resulted in 10-fold decay in HIV reservoir. Collectively, these results provide strong evidence for a pivotal role of IL-10 in HIV persistence, and a potential therapeutic strategy for HIV cure.

immunology↗