Analysis of flavor substances changes during fermentation of Chinese spicy cabbage based on GC-IMS and PCA.

This study employed a combination of principal component analysis (PCA) and gas chromatography-ion mobility spectrometry (GC-IMS) to examine the distinctive taste mixtures produced by Chinese spicy cabbage (CSC) fermented at varying temperatures. As the fermentation progressed, the pH gradually decreased and stabilized after the 11 days of fermentation, and the total content of organic acids and short-chain fatty acids increased. A total of 49 volatile mixtures were detected during CSC fermentation and storage for 21 days. These included 7 aldehydes, 6 alcohols, 7 esters, 6 ketones, 5 pyrazines, 4 sulfides, 4 phenols, 2 ethers, 2 olefins, and 1 acid. With time, the content of most volatile flavor substances decreased. PCA of the signal intensities of the volatile chemicals in the samples showed significant differences in the flavor of CSC fermented at different temperatures; consequently, the samples fermented at different temperatures were effectively separated in relatively independent regions of CSC. Therefore, low-temperature fermentation and storage at 4 °C were more suitable for CSC. Based on the identified volatile chemicals, HS-GC-IMS and PCA could effectively construct the flavour fingerprints of CSC samples. This study provided a theoretical basis for improving the fermentation quality of CSC.

Refractory wastewater shapes bacterial assembly and key taxa during long-term acclimatization.

Bacterial assembly and key taxa during long-term acclimatization in refractory wastewater treatment systems is of paramount importance for optimizing system performance and improving management strategies. Therefore, this study employed high-throughput sequencing, coupled with machine learning models and statistical analysis approaches, to comprehensively elucidate key features of bacterial communities and assembly processes in pesticide wastewater treatment systems. A nine-month monitoring showed substantial variation in diversity and composition of bacterial community between two interconnected biological treatment units (designated as BA and PA). Dynamics of bacterial communities in both units were similar. Moreover, water quality played crucial roles in regulating the bacterial community structure of activated sludge, which were primarily driven by deterministic patterns. Homogeneous selection contributed to 62.85 % and 64.43 % of the variations in BA and PA samples, respectively. Additionally, network analysis revealed significant modularity in bacterial compositions in both groups. Linear regression analysis identified major bacterial modules associated with metabolism and degradation functions. Notably, Module 2 in PA samples has significant positive correlations with functions related to metabolism of nucleotide, amino acid, and xenobiotics, as well as benzoate degradation. Furthermore, key taxa in ecological modules identified by Random Forest model, such as Pseudomonas, Sphingobium, and PHOS-HE28, were dominant populations with metabolism and degradation functions. Particularly, Sphingobium, appeared to be a potential multifunctional degrading bacterium, related to amino acid and xenobiotics metabolism, as well as fatty acid, valine, leucine, isoleucine, fluorobenzoate, and aminobenzoate degradation. These findings are important for developing operating strategies to maintain stable system performance during refractory wastewater treatment.

Genome-wide simple sequence repeat analysis and specific molecular marker development of rye.

BACKGROUND: Rye (Secale cereale L.) is the most widely used related species in wheat genetic breeding, and the introduction of its chromosome fragments into the wheat genome through distant hybridization is essential for enriching the genetic diversity of wheat. Rapid and accurate detection of rye chromatin in the wheat genome is important for distant hybridization. Simple sequence repeats (SSRs) are widely distributed in the genome, and SSRs of different species often exhibit species-specific characteristics. RESULTS: In this study, genome-wide SSRs in rye were identified, and their characteristics were outlined. A total of 997,027 SSRs were selected, with a density of 115.97 SSRs/Mb on average. There was no significant difference in the number of SSRs on each chromosome. The number of SSRs on 2R was the highest (15.29%), and the number of SSRs on 1R was the lowest (13.02%). The number of SSRs on each chromosome is significantly correlated with chromosome length. The types of SSR motifs were abundant, and each type of SSR was distributed on 7 chromosomes of rye. The numbers of mononucleotide simple sequence repeats (MNRs), dinucleotide simple sequence repeats (DNRs), and trinucleotide simple sequence repeats (TNRs) were the greatest, accounting for 46.90%, 18.37%, and 22.64% of the total number, respectively. Among the MNRs, the number of G/C repeats and the number of 10 bp motifs were the greatest, accounting for 26.24% and 31.32% of the MNRs, respectively. Based on the SSR sequences, a total of 657 pairs of primers were designed. The PCR results showed that 119 pairs of these primers were rye-specific and could effectively detect rye chromatin in the wheat genome. Moreover, 86 pairs of the primers could also detect one or more specific rye chromosomes. CONCLUSION: These results lay a foundation for both genomic evolution studies of rye and molecular breeding in wheat.

Discovery of pyrrolo[2,3-d]pyrimidin-4-one derivative YCH3124 as a potent USP7 inhibitor for cancer therapy.

USP7 is one of the most studied deubiquitinating enzymes, which is involved in the regulation of multiple cell signaling pathways and has been shown to be associated with the occurrence and progression of a variety of cancers. Inhibitors targeting USP7 have been studied by several teams, but most of them lack selectivity and have low activities. Herein, we reported a serious of pyrrole[2,3-d]pyrimidin-4-one derivatives through scaffold hopping of recently reported 4-hydroxypiperidine compounds. The representative compound Z33 (YCH3124) exhibited highly potent USP7 inhibition activity as well as anti-proliferative activity against four kinds of cancer cell lines. Further study revealed that YCH3124 effectively inhibited the downstream USP7 pathway and resulted in the accumulation of both p53 and p21 in a dose-dependent manner. Notably, YCH3124 disrupted cell cycle progression through restricting G1 phase and induced significant apoptosis in CHP-212 cells. In summary, our efforts provided a series of novel pyrrole[2,3-d]pyrimidin-4-one analogs as potent USP7 inhibitors with excellent anti-cancer activity.

Targeting Neuronal GPR65 With Delayed BTB09089 Treatment Improves Neurorehabilitation Following Ischemic Stroke.

BACKGROUND: GPR65 (G protein-coupled receptor 65) can sense extracellular acidic environment to regulate pathophysiological processes. Pretreatment with the GPR65 agonist BTB09089 has been proven to produce neuroprotection in acute ischemic stroke. However, whether delayed BTB09089 treatment and neuronal GPR65 activation promote neurorestoration remains unknown. METHODS: Ischemic stroke was induced in wild-type (WT) or GPR65 knockout (GPR65-/-) mice by photothrombotic ischemia. Male mice were injected intraperitoneally with BTB09089 every other day at days 3, 7, or 14 poststroke. AAV-Syn-GPR65 (adenoassociated virus-synapsin-GPR65) was utilized to overexpress GPR65 in the peri-infarct cortical neurons of GPR65-/- and WT mice. Motor function was monitored by grid-walk and cylinder tests. The neurorestorative effects of BTB09089 were observed by immunohistochemistry, Golgi-Cox staining, and Western blotting. RESULTS: BTB09089 significantly promoted motor outcomes in WT but not in GPR65-/- mice, even when BTB09089 was delayed for 3 to 7 days. BTB09089 inhibited the activation of microglia and glial scar progression in WT but not in GPR65-/- mice. Meanwhile, BTB09089 reduced the decrease in neuronal density in WT mice, but this benefit was abolished in GPR65-/- mice and reemerged by overexpressing GPR65 in peri-infarct cortical neurons. Furthermore, BTB09089 increased the GAP43 (growth-associated protein-43) and synaptophysin puncta density, dendritic spine density, dendritic branch length, and dendritic complexity by overexpressing GPR65 in the peri-infarct cortical neurons of GPR65-/- mice, which was accompanied by increased levels of p-CREB (phosphorylated cAMP-responsive element-binding protein). In addition, the therapeutic window of BTB09089 was extended to day 14 by overexpressing GPR65 in the peri-infarct cortical neurons of WT mice. CONCLUSIONS: Our findings indicated that delayed BTB09089 treatment improved neurological functional recovery and brain tissue repair poststroke through activating neuronal GRP65. GPR65 overexpression may be a potential strategy to expand the therapeutic time window of GPR65 agonists for neurorehabilitation after ischemic stroke.

Physical and psychological status of emergency assistance personnel at major public health events: a qualitative descriptive study.

BACKGROUND: Many personnel respond to natural disasters like earthquakes and tsunamis and frequent public health events like Ebola and COVID-19. However, research on emergency assistance personnel remains limited. This study aims to describe the perceived well-being among responders deployed in isolated or emergency international missions while providing practical references to intervene in developing similar missions. METHODS: For this qualitative phenomenological study, purposive sampling was used following the principle of maximum differentiation to select personnel deployed on an emergency mission for over a year. Data collection continued until data saturation. Phenomenologically semi-structured interviews helped explore the physical and psychological status of the participants with Colaizzi's method. RESULTS: Eleven personnel were interviewed after the mission, with four major themes being identified: 'perceived somatic change,' 'perceived emotional change,' 'behavioral change,' and 'coping with perceived change.' CONCLUSIONS: The mental health status of the emergency assistance personnel was affected by multiple factors from external and internal environments. The current study explored the physical and psychological feelings and emotions of emergency assistance personnel during an emergency mission. The study provided a practical reference for health management under similar missions. REGISTRATIONS: Not registered.

Targeting astrocytic TDAG8 with delayed CO2 postconditioning improves functional outcomes after controlled cortical impact injury in mice.

T-cell death-associated gene 8 (TDAG8), a G-protein-coupled receptor sensing physiological or weak acids, regulates inflammatory responses. However, its role in traumatic brain injury (TBI) remains unknown. Our recent study showed that delayed CO2 postconditioning (DCPC) has neuroreparative effects after TBI. We hypothesized that activating astrocytic TDAG8 is a key mechanism for DCPC. WT and TDAG8-/- mice received DCPC daily by transiently inhaling 10% CO2 after controlled cortical impact (CCI). HBAAV2/9-GFAP-m-TDAG8-3xflag-EGFP was used to overexpress TDAG8 in astrocytes. The beam walking test, mNSS, immunofluorescence and Golgi-Cox staining were used to evaluate motor function, glial activation and dendritic plasticity. DCPC significantly improved motor function; increased total dendritic length, neuronal complexity and spine density; inhibited overactivation of astrocytes and microglia; and promoted the expression of astrocytic brain-derived neurotrophic factor in WT but not TDAG8-/- mice. Overexpressing TDAG8 in astrocytes surrounding the lesion in TDAG8-/- mice restored the beneficial effects of DCPC. Although the effects of DCPC on Days 14-28 were much weaker than those of DCPC on Days 3-28 in WT mice, these effects were further enhanced by overexpressing astrocytic TDAG8. Astrocytic TDAG8 is a key target of DCPC for TBI rehabilitation. Its overexpression is a strategy that broadens the therapeutic window and enhances the effects of DCPC.

Developing a microbial community structure index (MCSI) as an approach to evaluate and optimize bioremediation performance.

Much attention is placed on organohalide-respiring bacteria (OHRB), such as Dehalococcoides, during the design and performance monitoring of chlorinated solvent bioremediation systems. However, many OHRB cannot function effectively without the support of a diverse group of other microbial community members (MCMs), who play key roles fermenting organic matter into more readily useable electron donors, producing corrinoids such as vitamin B12, or facilitating other important metabolic processes or biochemical reactions. While it is known that certain MCMs support dechlorination, a metric considering their contribution to bioremediation performance has yet to be proposed. Advances in molecular biology tools offer an opportunity to better understand the presence and activity of specific microbes, and their relation to bioremediation performance. In this paper, we test the hypothesis that a specific microbial consortium identified within 16S ribosomal ribonucleic acid (rRNA) gene next generation sequencing (NGS) data can be predictive of contaminant degradation rates. Field-based data from multiple contaminated sites indicate that increasing relative abundance of specific MCMs correlates with increasing first-order degradation rates. Based on these results, we present a framework for computing a simplified metric using NGS data, the Microbial Community Structure Index, to evaluate the adequacy of the microbial ecosystem during assessment of bioremediation performance.

Causality of inflammatory bowel disease and seborrheic keratosis: A bidirectional two-sample Mendelian randomization study.

BACKGROUND: Previous studies have revealed a potential link between inflammatory bowel disease (IBD) and seborrheic keratosis (SK). However, whether this association is causal or confounded remains unknown. METHODS: We conducted this two-sample Mendelian randomization (TSMR) analysis to clarify bidirectional causality between IBD, including its two primary conditions Crohn's disease (CD) and ulcerative colitis (UC), and SK. The summary genetic data of IBD, CD, UC and SK were obtained from accessible genome-wide association studies (GWAS). This TSMR study was primarily performed using inverse-variance weighted (IVW) method, complemented by MR-Egger, weighted median (WM), Bayesian weighted MR (BWMR), MR-robust adjusted profile score (MR-RAPS), MR-pleiotropy residual sum and outlier (MR-PRESSO), and radial IVW MR analyses with modified second-order weights (IVW [Mod 2nd]) methods. Assessment of sensitivity and identification of potential outliers were subsequently conducted to aid interpretation of results. RESULTS: The forward MR results showed that IBD [odds ratio (OR) = 1.068, 95% confidence interval (CI) = 1.010-1.129, p = 0.020) and its subtype CD (OR = 1.088, 95%CI = 1.038-1.139, p < 0.001) increased the risk of SK. However, the occurrence of SK could not be affected by UC (OR = 1.090, 95%CI = 0.977-1.216, p = 0.123). In the reverse analysis, no causal relationship between SK and IBD (OR = 0.905, 95%CI = 0.813-1.008, p = 0.069), UC (OR = 0.959, 95%CI = 0.860-1.068, p = 0.443), and CD (OR = 0.933, 95%CI = 0.846-1.029, p = 0.165) was identified. CONCLUSION: These findings demonstrate that IBD and its subtype CD could increase the incidence of SK in European populations, whereas SK does not affect IBD occurrence.

Ferroelectric modulation of CuCo2O4 nanorods for controllable alkaline water electrolysis.

As a technology for emerging environmental applications, water electrolysis is a significant approach for producing clean hydrogen energy. In this work, we used an efficacious piezoelectric method to significantly improve the catalytic water splitting activity without affecting the morphology as well as the components by altering the bulk charge separation state inside the material. The obtained CuCo2O4 nanorods were treated under a corona polarization apparatus, which significantly enhanced ferroelectricity relative to that before the polarization increasing the physical charge separation and piezoelectric potential energy, enhancing the green hydrogen production. The polarized CuCo2O4 nanorods exhibit excellent water electrolysis performance under alkaline conditions, with hydrogen evolution overpotential of 78.7 mV and oxygen evolution overpotential of 299 mV at 10 mA cm-2, which is much better than that of unpolarized CuCo2O4 nanorods. Moreover, the Tafel slopes of polarized CuCo2O4 nanorods are 86.9 mV dec-1 in the HER process and 73.1 mV dec-1 in the OER process, which are much lower than commercial catalysts of Pt/C (88.0 mV dec-1 for HER) or RuO2 (78.5 mV dec-1 for OER), proving faster kinetic on polarized CuCo2O4 nanorods due to their higher electroconductibility and intrinsic activity. In particular, polarized CuCo2O4 nanorods are identified as promising catalysts for water electrolysis with robust stability, offering outstanding catalytic performance and excellent energy efficiency.

Causal associations between the gut microbiota and multiple myeloma: a two-sample Mendelian randomization study.

Background: Previous observational studies have indicated a potential association between the gut microbiota and multiple myeloma (MM). However, the relationship between the gut microbiota and MM remains unclear. This study aimed to ascertain the existence of a causal link between the gut microbiota and MM. Methods: To investigate the potential causal relationship between gut microbiota and MM, a two-sample Mendelian randomization (MR) analysis was conducted. Exposure data was obtained from the MiBioGen consortium, which provided genetic variants associated with 211 bacterial traits. MM outcome data was obtained from the FinnGen consortium. The selection of Single nucleotide polymorphisms estimates was performed through meta-analysis using inverse-variance weighting, and sensitivity analyses were conducted using weighted median, MR Egger, Simple mode, and MR-PRESSO. Results: The results of the study demonstrated a significant positive correlation between the genus Eubacterium ruminantium group and the risk of MM (OR 1.71, 95% CI 1.21 to 2.39). Conversely, the genus: Dorea (OR 0.46, 95% CI 0.24 to 0.86), Coprococcus1 (OR 0.47, 95% CI 0.22 to 1.00), RuminococcaceaeUCG014 (OR 0.57, 95% CI 0.33 to 0.99), Eubacterium rectale group (OR 0.37, 95% CI 0.18 to 0.77), and order: Victivallales (OR 0.62, 95% CI 0.41-0.94), class: Lentisphaeria (OR 0.62, 95% CI 0.41 to 0.94), exhibited a negative association with MM. The inverse variance weighting analysis provided additional support for these findings. Conclusion: This study represents an inaugural exploration of MR to investigate the connections between gut microbiota and MM, thereby suggesting potential significance for the prevention and treatment of MM.

Advance on Chinese Medicine for Hypertensive Renal Damage: Focus on the Complex Molecular Mechanisms.

Hypertensive renal damage (HRD) is a major cause of end-stage renal disease. Among the causes of end-stage renal disease, HRD accounts for nearly 34% of the total number of cases. Antihypertensive treatment is primarily drug-based, but therapeutic efficacy is less effective and can have serious side effects. Chinese medicine (CM) has significant advantages in the treatment of HRD. CM is rich in various active ingredients and has the property of targeting multiple targets and channels. Therefore, the regulatory network of CM on disease is complex. A large number of CM have been employed to treat HRD, either as single applications or as part of compound formulations. The key possible mechanisms of CM for HRD include regulation of the renin-angiotensin-aldosterone system, antioxidation, anti-inflammation, rescue of endothelial function, regulation of vasoactive substance secretion and obesity-related factors, etc. This review summarized and discussed the recent advance in the basic research mechanisms of CM interventions for HRD and pointed out the challenges and future prospects.

Comprehensive analysis of endoplasmic reticulum stress related signature in head and neck squamous carcinoma.

Head and neck squamous carcinoma (HNSC) is a prevalent malignant disease, with the majority of patients being diagnosed at an advanced stage. Endoplasmic reticulum stress (ERS) is considered to be a process that promotes tumorigenesis and impacts the tumor microenvironment (TME) in various cancers. The study aims to investigate the predictive value of ERS in HNSC and explore the correlation between ERS-related genes and TME. A series of bioinformatics analyses were carried out based on mRNA and scRNA-seq data from the TCGA and GEO databases. We conducted RT-qPCR and western blot to validate the signature, and performed cell functional experiments to investigate the in vitro biological functions of the gene. We identified 63 ERS-related genes that were associated with outcome and stage in HNSC. A three-gene signature (ATF6, TRIB3, and UBXN6) was developed, which presents predictive value in the prognosis and immunotherapy response of HNSC patients. The high-risk group exhibited a worse prognosis but may benefit from immunotherapy. Furthermore, there was a significant correlation between the signature and immune infiltration. In the high-risk group, fibroblasts were more active in intercellular communication, and more T cells were observed at the end of the sequential phase. The genes in the ERS-related signature were overexpressed in HNSC cells, and the knockdown of TRIB3 significantly inhibited cell proliferation and migration. This study established a novel ERS-related signature that has potential implications for HNSC therapy and the understanding of TME.

SPARCL1 promotes chondrocytes extracellular matrix degradation and inflammation in osteoarthritis via TNF/NF-κB pathway.

Objectives: SPARCL1 is a matricellular protein that mediates the cell-matrix interactions and participates in physiological processes such as cell adhesion, differentiation and proliferation. However, its role in chondrocyte and osteoarthritis (OA) progression has not been fully characterized. We aimed to evaluate the effects of SPARCL1 on OA through in vitro and in vivo experiments. Methods: Expression of SPARCL1 was examined in 55 paired human OA samples. Effects of Sparcl1 on chondrocytes were identified in vitro. Intra-articular injection was performed in an anterior cruciate ligament transection (ACLT) mouse model. Alterations of SPARCL1-mediated signaling pathway were identified by RNA-seq analysis. qPCR and western-blot were used to demonstrate the potential signaling pathway. Results: SPARCL1 expression in the OA cartilage was increased compared with undamaged cartilage. Recombinant Sparcl1 protein induced extracellular matrix degradation in chondrocytes. Furthermore, intra-articular injection of recombinant Sparcl1 protein in ACLT mice could promote OA pathogenesis. Mechanistically, Sparcl1 activated TNF/NF-κB pathway and consequently led to increased transcription of inflammatory factors and catabolism genes of cartilage, which could be reversed by NF-κB inhibitor BAY 11-7082. Conclusion: SPARCL1 could promote extracellular matrix degradation and inflammatory response to accelerate OA progression via TNF/NF-κB pathway. The translational potential of this article: The current research could help to gain further insights into the underlying molecular mechanism in OA development, and provides a biological rationale for the use of SPARCL1 as a potential therapeutic target of OA.

An emerging antibacterial nanovaccine for enhanced chemotherapy by selectively eliminating tumor-colonizing bacteria.

Fusobacterium nucleatum (F. nucleatum), an oral anaerobe, is prevalent in colorectal cancer and is closely related to increased cancer cell growth, metastasis, and poor treatment outcomes. Bacterial vaccines capable of selectively eliminating bacteria present a promising approach to targeting intratumor F. nucleatum, thereby enhancing cancer treatment. Although adjuvants have been employed to enhance the immune response, the vaccine's effectiveness is constrained by inadequate T-cell activation necessary for eradicating intracellular pathogens. In this study, we developed a minimalistic, biomimetic nanovaccine by integrating highly immunostimulatory adjuvant cholesterol-modified CpG oligonucleotides into the autologously derived F. nucleatum membranes. Compared to the traditional vaccines consisting of inactivated bacteria and Alum adjuvant, the nanovaccine coupled with bacterial membranes and adjuvants could remarkably improve multiple antigens and adjuvant co-delivery to dendritic cells, maximizing their ability to achieve effective antigen presentation and strong downstream immune progress. Notably, the nanovaccine exhibits outstanding selective prophylactic and therapeutic effects, eliminating F. nucleatum without affecting intratumoral and gut microbiota. It significantly enhances chemotherapy efficacy and reduces cancer metastasis in F. nucleatum-infected colorectal cancer. Overall, this work represents the rational application of bacterial nanovaccine and provides a blueprint for future development in enhancing the antitumor effect against bacterial-infected cancer.

Anisotropic Galvanomagnetic Effects in Single Cubic Crystals: A Theory and Its Verification.

A theory of anisotropic galvanomagnetic effects in single cubic crystals and its experimental verifications are presented for the current in the (001) plane. In contrast to the general belief that galvanomagnetic effects in single crystals are highly sensitive to many internal and external effects and have no universal features, the theory predicts universal angular dependencies of longitudinal and transverse resistivity and various characteristics when magnetization rotates in the (001) plane, the plane perpendicular to the current, and the plane containing the current and [001] direction. The universal angular dependencies are verified by experiments on Fe_{30}Co_{70} single cubic crystal film. The findings provide new avenues for fundamental research and applications of galvanomagnetic effects, because single crystals offer advantages over polycrystalline materials for band structure and crystallographic orientation engineering.

Meta-analysis of the association between interleukin-17 and ischemic cardiovascular disease.

BACKGROUND: Interleukin-17 (IL-17) has been hypothesized to be involved in ischemic cardiovascular disease (ICVD). However, the association of IL-17 with ICVD remained unclear. The aim of this study was to systematically analyze the available evidence regarding the association between IL-17 and ICVD. METHODS: We searched the PubMed, Web of Science, Cochrane Library, and Embase databases up to October 2023 to identify publications on the association between IL-17 and ICVD. The merged results were analyzed using a random effects model for meta-analysis and subgroup analysis. RESULTS: A total of 955 publications were initially identified in our search and screened; six studies were eventually included in the analysis. The average age of study participants was 60.3 ± 12.6 years and 65.5% were men. There was a high degree of heterogeneity among studies. The results showed that IL-17 level were higher in the case group than those in the control group (standardized mean difference, SMD = 1.60, 95% confidence interval (95% CI): 0.53-2.66, P = 0.003). In sensitivity analysis, the merged results showed good robustness. Additionally, subgroup analysis showed that race and ethnicity, sample size, and detection methods were significant factors influencing heterogeneity in the published studies. CONCLUSION: Our finding revealed that increased IL-17 level contributed to the development of ICVD, suggesting IL-17 as a potential risk marker. Further research is needed to establish IL-17 as a therapeutic biomarker of ICVD.

Detection of Bartonella spp. in farmed deer (Artiodactyla: Cervidae) using multiplex assays in the Qinghai-Tibet Plateau, China.

In this study, we investigated the prevalence of Bartonella in deer from Qilian County, Qinghai Province, China. Blood samples were collected from 69 red deer, 40 white-lipped deer, and 27 sika deer. The detection of Bartonella spp. has been conducted. The overall prevalence of Bartonella was 33.6% (46/135). Species-specific prevalence was 50.72% in red deer (35/69), 20.00% in white-lipped deer (8/40), and 11.11% in sika deer (3/27). There were significant differences in the prevalence rates among the different species of deer. The amplicon sequence comparison revealed a high homology of the ruminant-associated Bartonella spp. Nanopore sequencing further confirmed the results. Bartonella reads were presented in each of the qPCR-positive samples. Phylogenetic analysis indicated that the Bartonella sequences detected in deer blood were closely related to ruminant-borne Bartonella spp. In summary, we reported the Bartonella prevalence of different deer species in Qinghai, and there were at least one species of ruminant-associated Bartonella, B. schoenbuchensis. IMPORTANCE: This is the first report about Bartonella infections in the deer population from China. We found that there were two species of Bartonella and an unidentified species of Bartonella among the unculturing strains carried by these deer populations. We first used Nanopore sequencing to detect Bartonella from deer blood samples and indicated that Nanopore sequencing is beneficial to detect pathogens due to its advantage of real-time and high sensitivity.

Overexpression of wild-type HRAS drives non-alcoholic steatohepatitis to hepatocellular carcinoma in mice.

Hepatocellular carcinoma (HCC), a prevalent solid carcinoma of significant concern, is an aggressive and often fatal disease with increasing global incidence rates and poor therapeutic outcomes. The etiology and pathological progression of non-alcoholic steatohepatitis (NASH)-related HCC is multifactorial and multistage. However, no single animal model can accurately mimic the full NASH-related HCC pathological progression, posing considerable challenges to transition and mechanistic studies. Herein, a novel conditional inducible wild-type human HRAS overexpressed mouse model (HRAS-HCC) was established, demonstrating 100% morbidity and mortality within approximately one month under normal dietary and lifestyle conditions. Advanced symptoms of HCC such as ascites, thrombus, internal hemorrhage, jaundice, and lung metastasis were successfully replicated in mice. In-depth pathological features of NASH- related HCC were demonstrated by pathological staining, biochemical analyses, and typical marker gene detections. Combined murine anti-PD-1 and sorafenib treatment effectively prolonged mouse survival, further confirming the accuracy and reliability of the model. Based on protein-protein interaction (PPI) network and RNA sequencing analyses, we speculated that overexpression of HRAS may initiate the THBS1-COL4A3 axis to induce NASH with severe fibrosis, with subsequent progression to HCC. Collectively, our study successfully duplicated natural sequential progression in a single murine model over a very short period, providing an accurate and reliable preclinical tool for therapeutic evaluations targeting the NASH to HCC continuum.