Multi-omic analysis tools for microbial metabolites prediction.

How to resolve the metabolic dark matter of microorganisms has long been a challenging problem in discovering active molecules. Diverse omics tools have been developed to guide the discovery and characterization of various microbial metabolites, which make it gradually possible to predict the overall metabolites for individual strains. The combinations of multi-omic analysis tools effectively compensates for the shortcomings of current studies that focus only on single omics or a broad class of metabolites. In this review, we systematically update, categorize and sort out different analysis tools for microbial metabolites prediction in the last five years to appeal for the multi-omic combination on the understanding of the metabolic nature of microbes. First, we provide the general survey on different updated prediction databases, webservers, or software that based on genomics, transcriptomics, proteomics, and metabolomics, respectively. Then, we discuss the essentiality on the integration of multi-omics data to predict metabolites of different microbial strains and communities, as well as stressing the combination of other techniques, such as systems biology methods and data-driven algorithms. Finally, we identify key challenges and trends in developing multi-omic analysis tools for more comprehensive prediction on diverse microbial metabolites that contribute to human health and disease treatment.

Seven Tesla Evidence for Columnar and Rostral-Caudal Organization of the Human Periaqueductal Gray Response in the Absence of Threat: A Working Memory Study.

The periaqueductal gray (PAG) is a small midbrain structure that surrounds the cerebral aqueduct, regulates brain-body communication, and is often studied for its role in "fight-or-flight" and "freezing" responses to threat. We used ultra-high-field 7 T fMRI to resolve the PAG in humans and distinguish it from the cerebral aqueduct, examining its in vivo function during a working memory task (N = 87). Both mild and moderate cognitive demands elicited spatially similar patterns of whole-brain blood oxygenation level-dependent (BOLD) response, and moderate cognitive demand elicited widespread BOLD increases above baseline in the brainstem. Notably, these brainstem increases were not significantly greater than those in the mild demand condition, suggesting that a subthreshold brainstem BOLD increase occurred for mild cognitive demand as well. Subject-specific masks were group aligned to examine PAG response. In PAG, both mild and moderate demands elicited a well-defined response in ventrolateral PAG, a region thought to be functionally related to anticipated painful threat in humans and nonhuman animals-yet, the present task posed only the most minimal (if any) "threat," with the cognitive tasks used being approximately as challenging as remembering a phone number. These findings suggest that the PAG may play a more general role in visceromotor regulation, even in the absence of threat.

Analysis of the prevalence and clinical features of respiratory syncytial virus infection in a pediatric hospital in Zhejiang Province from 2019 to 2023.

The aim of this study was to investigate the epidemiological characteristics of respiratory syncytial virus (RSV) infections in children in Zhejiang from 2019 to 2023. Data from pediatric patients who visited the Children's Hospital of Zhejiang University School of Medicine for RSV infection between 2019 and 2023 were analyzed. Nasopharyngeal swabs were collected for RSV antigen detection, and relevant patient information was collected. Factors such as age were analyzed. A total of 673 094 specimens were included from 2019 to 2023, with a rate of positive specimens of 4.74% (31 929/673 094). The highest rate of positive specimens of 10.82%, was recorded in 2021, while the remaining years had a rate of approximately 3%-5%. In terms of seasonal prevalence characteristics, the rate of positive specimens in 2019, 2020, and 2022 peaked in the winter months at approximately 8% and decreased in the summer months, where the rate of positive specimens remained at approximately 0.5%. In contrast, summer is the peak period for RSV incidence in 2021 and 2023, with the rate of positive specimens being as high as 9%-12%. Based on the prevalence characteristics of gender and age, this study found that the detection rate of positive specimens was higher in boys than in girls in 2019-2023. In 2019-2022, among the different age groups, the highest rate of positive specimens was found in children aged 0 to <6 months, and it decreased with age. In 2023, the rate of positive specimens was above 8% in the 0 to <6 months, 6 to <12 months, and 1-2 years age groups, with the highest rate of positive specimens in the 1-2 years age group, and a gradual decrease in the rate of positive specimens with age for children over 3 years of age. Between 2019 and 2023, the epidemiological pattern of RSV changed. A summer peak was observed in 2021 and 2023.

Diagnosis and management of urinary bladder paragangliomas: A Sino-American-European retrospective observational study.

OBJECTIVE: Paragangliomas of the urinary bladder (UBPGLs) are rare neuroendocrine tumours and pose a diagnostic and surgical challenge. It remains unclear what factors contribute to a timely presurgical diagnosis. The purpose of this study is to identify factors contributing to missing the diagnosis of UBPGLs before surgery. DESIGN, PATIENTS AND MEASUREMENTS: A total of 73 patients from 11 centres in China, and 51 patients from 6 centres in Europe and 1 center in the United States were included. Clinical, surgical and genetic data were collected and compared in patients diagnosed before versus after surgery. Logistic regression analysis was used to identify clinical factors associated with initiation of presurgical biochemical testing. RESULTS: Among all patients, only 47.6% were diagnosed before surgery. These patients were younger (34.0 vs. 54.0 years, p < .001), had larger tumours (2.9 vs. 1.8 cm, p < .001), and more had a SDHB pathogenic variant (54.7% vs. 11.9%, p < .001) than those diagnosed after surgery. Patients with presurgical diagnosis presented with more micturition spells (39.7% vs. 15.9%, p = .003), hypertension (50.0% vs. 31.7%, p = .041) and catecholamine-related symptoms (37.9% vs. 17.5%, p = .012). Multivariable logistic analysis revealed that presence of younger age (<35 years, odds ratio [OR] = 6.47, p = .013), micturition spells (OR = 6.79, p = .007), hypertension (OR = 3.98, p = .011), and sweating (OR = 41.72, p = .013) increased the probability of initiating presurgical biochemical testing. CONCLUSIONS: Most patients with UBPGL are diagnosed after surgery. Young age, hypertension, micturition spells and sweating are clues in assisting to initiate early biochemical testing and thus may establish a timely presurgical diagnosis.

Effect of community-based public health service on health-related quality of life among middle-aged and older adults with chronic diseases in China.

BACKGROUND: The growing prevalence of non-communicable chronic diseases poses a significant public health challenge globally, particularly impacting the well-being of aging populations. This study aims to assess the impact of community-based public health service (PHS) on the health-related quality of life (HRQoL) among middle-aged and older adults with chronic diseases in China. METHODS: Utilizing data from the China Health and Retirement Longitudinal Study, we constructed a novel scale based on the 36-Item Short Form Health Survey (SF-36) to measure the HRQoL of middle-aged and older patients with hypertension and/or type-2 diabetes. Multivariate linear regression models with Instrument Variables and Propensity Score Matching techniques were applied to examine the effect of PHS on the HRQoL of identified chronic disease patients. RESULTS: Among 8,403 hypertensive and/or diabetic patients, only 10.98% had received PHS. After adjusting for covariates, PHS exhibited a significant association with an elevated overall SF-36 score (ß = 3.539, p < 0.001). Similar effects were observed in the physical and mental component summary scores, with increases of 1.982 (p < 0.001) and 5.095 (p < 0.001), respectively. Sensitive analysis affirmed the robustness of these findings. Heterogeneity analysis revealed significant HRQoL improvements among males, females, those aged 70 and older, patients with comorbidities, and urban residents, while the effect was less pronounced in the middle-aged, those without comorbidities, or rural dwellers. CONCLUSION: Community-based PHS has exerted a positive impact on both the physiological and psychological aspects of HRQoL among middle-aged and older chronic disease patients, with effects varying among individuals with different characteristics. Our findings advocate for enhancing the delivery and utilization of government-funded PHS, increasing health literacy, and promoting early prevention strategies for chronic diseases. Furthermore, targeted health management initiatives for patients with comorbidities and enhancements in the quality of community healthcare services, particularly in rural areas, are deemed necessary.

Development and validation of a scale to measure the care needs of Crohn's disease patients: a mixed-methods study.

BACKGROUND: Crohn's disease (CD) patients require varying levels of supportive care. In order to facilitate caregivers and nurses in precisely evaluating the caregiving requirements of these patients, we developed the CD-specific Care Needs Scale (CD-CNS). METHODS: This study employed a mixed-methods approach, integrating qualitative and quantitative methodologies. The initial items of the scale were developed through qualitative interviews, Delphi expert consultation, and literature review, while the final items were refined through clinical testing. Qualitative interviews were conducted based on the supportive care needs framework and Maslow's hierarchy of needs, and scale items were constructed through a literature search and qualitative interviews. The initial version of the scale with 45 items was obtained after the items were verified and modified by expert consultation. A total of 250 CD patients admitted to the gastroenterology department of a hospital in China were selected for verification of the initial version of the scale. A self-designed general questionnaire was used to obtain patients' medical history and sociodemographic data, and the Chinese version of the Inflammatory Bowel Disease Questionnaire (IBDQ) was used as the criterion. Exploratory factor analysis (EFA) was performed on the CD-CNS to evaluate the dimensions, factor structure, reliability, criterion validity, and construct validity. RESULTS: EFA identified 5 dimensions and retained 27 items with strong internal consistency reliability (α = 0.940). The Cronbach's α coefficients for each dimension ranged from 0.824 to 0.921. Criterion validity was assessed using Spearman's coefficient, which demonstrated a significant correlation with the IBDQ (P < 0.050). The test-retest reliability for each dimension after two weeks ranged from 0.655 to 0.895. CONCLUSIONS: We developed and validated a new scale that can be used to assess the care needs of CD patients. This new tool can guide the specific supportive care of CD patients. TRIAL REGISTRATION: This study was reviewed and approved by the Ethics Committee of the Second Hospital of Nanjing (2021-LS-ky-022). The study was duly registered and approved online through the Trial Center of the Second Hospital of Nanjing in 2021. Confidentiality was ensured by anonymizing all the data. The entire study process was conducted under the supervision of the Ethics Committee of Nanjing Second Hospital. Informed consent was obtained from the patients, and each patient volunteered and agreed to participate.

The role of microbial interactions in dental caries: Dental plaque microbiota analysis.

OBJECTIVES: Dental caries is a result of the ecological dysfunction of the polymicrobial community on the tooth surface, which evolves through microbial interactions. In this study, we conducted a thorough analysis of the dental plaque microbiome to comprehend its multi-microbial aetiology. MATERIALS AND METHOD: In this study, plaque was collected from healthy tooth surfaces, shallow carious teeth and deep carious teeth, and bacterial composition and abundance were assessed using 16S rRNA high-throughput sequencing. Random forest and LEfSe were used to profile various microorganisms at each stage. Additionally, we developed a molecular ecological network (MEN) based on random matrix theory (RMT) to examine microbial interactions for the first time. RESULTS: Our results reveal that Scardovia wiggsiae, Streptococcus mutans, and Propionibacterium acidifaciens may be associated with initial caries, and Propionibacterium acidifaciens differentiates between shallow and deep caries. As caries progressed, the alpha diversity index declined, indicating a decrease in microbial variety. The network topological indices such as centralization betweenness revealed that the caries network had become more complex, involving more microbial interactions. The shallow network revealed a high negative correlation ratio across nodes, indicating that microbes competed heavily. In contrast, the positive correlation ratio of deep network nodes was high, and microorganisms transitioned from a competitive to a synergistic state. CONCLUSIONS: This study suggests that microbial diversity and interactions are critical to caries progression and that future caries research should give greater consideration to the role of microbial interaction factors in caries progression.

PLAGL1 is associated with prognosis and cell proliferation in pancreatic adenocarcinoma.

BACKGROUND: Emerging evidence has shown the crucial roles of pleomorphic adenoma gene (PLAG) family genes in multiple cancers. However, their functions and mechanisms in pancreatic adenocarcinoma (PAAD) remain poorly understood. METHODS: We analyzed the expression levels of PLAG family genes in both The Cancer Genome Atlas (TCGA) database and a Gene Expression Omnibus (GEO) database, and confirmed the results in our three independent cohorts of 382 PAAD tissues and 362 adjacent nontumor pancreatic tissues. Integrated analyses were carried out to explore the function, mechanism and prognostic value of the selected PLAG family gene in PAAD patients. RESULTS: By analyzing the TCGA and GEO databases, PLAGL1 was identified to be downregulated in PAAD tissues, and its decreasing levels of both mRNA and protein were verified in our three independent PAAD cohorts. PLAGL1 expression was inversely correlated with clinicopathological factors including the Ki67+ cell rate and pathologic stage. Further GSEA of the TCGA-PAAD cohort demonstrated that multiple signaling pathways implicated in cell proliferation were enriched in the lower PLAGL1 expressing PAAD group. Moreover, we demonstrated that PLAGL1 expression was obviously negatively associated with patients' overall survival outcome in both the TCGA-PAAD cohort and our verification cohorts. Additionally, through MTS and BrdU assays, we further demonstrated in vitro that PLAGL1 had the impact of preventing the proliferation of pancreatic cancer cells. CONCLUSIONS: Our present study suggested that downregulated PLAGL1 might act as a biomarker in predicts poor prognosis and one of important factors in increasing cell proliferation in PAAD. This study provides us with a novel prognostic marker and therapeutic strategy for PAAD, which deserves further study.

Comparison of early postoperative outcomes between omega-like duct-to-mucosa pancreatojejunostomy and conventional duct-to-mucosa pancreatojejunostomy after pancreaticoduodenectomy.

BACKGROUND: Pancreatic fistula is a life-threatening complication of pancreaticoduodenectomy. Omega-like duct-to-mucosa pancreatojejunostomy is a novel technique which helps reduce the risk of fistulation. This study aimed to compare early postoperative outcomes of omega-like and conventional pancreatojejunostomy. METHODS: A retrospective single-centre cohort study comparing outcomes of adult patients who underwent open pancreatoduodenectomy with conventional (CDMP) or omega-like duct-to-mucosa pancreatojejunostomy (ODMP) between 1 January 2015 and 31 December 2019. The primary outcome measure was the pancreatic fistula rate. RESULTS: 440 patients were included in this study of whom 233 underwent CDMP and 207 ODMP. The rate of clinically relevant pancreatic fistula (grade B/C) was significantly higher after CDMP than ODMP (18.5% vs. 10.6%, P = 0.021). 153 patients in CDMP group and 99 patients in ODMP group developed one or more complications (65.7% vs. 47.8%, P = 0.004). The average hospitalization expenses were numerically decreased in ODMP group, although this was not statistically significant (120,000 ± 42,000 [Chinese Yuan] vs. 100,000 ± 40,000 [Chinese Yuan] or 18,581 ± 6503 [United States Dollar] vs. 15,484 ± 6194 [United States Dollar], P = 0.402). CONCLUSION: ODMP may reduce the incidence of pancreatic fistula and other early postoperative complications after pancreatoduodenectomy.

Circular RNA circSDHC serves as a sponge for miR-127-3p to promote the proliferation and metastasis of renal cell carcinoma via the CDKN3/E2F1 axis.

BACKGROUND: There is increasing evidence that circular RNAs (circRNAs) have significant regulatory roles in cancer development and progression; however, the expression patterns and biological functions of circRNAs in renal cell carcinoma (RCC) remain largely elusive. METHOD: Bioinformatics methods were applied to screen for circRNAs differentially expressed in RCC. Analysis of online circRNAs microarray datasets and our own patient cohort indicated that circSDHC (hsa_circ_0015004) had a potential oncogenic role in RCC. Subsequently, circSDHC expression was measured in RCC tissues and cell lines by qPCR assay, and the prognostic value of circSDHC evaluated. Further, a series of functional in vitro and in vivo experiments were conducted to assess the effects of circSDHC on RCC proliferation and metastasis. RNA pull-down assay, luciferase reporter and fluorescent in situ hybridization assays were used to confirm the interactions between circSDHC, miR-127-3p and its target genes. RESULTS: Clinically, high circSDHC expression was correlated with advanced TNM stage and poor survival in patients with RCC. Further, circSDHC promoted tumor cell proliferation and invasion, both in vivo and in vitro. Analysis of the mechanism underlying the effects of circSDHC in RCC demonstrated that it binds competitively to miR-127-3p and prevents its suppression of a downstream gene, CDKN3, and the E2F1 pathway, thereby leading to RCC malignant progression. Furthermore, knockdown of circSDHC caused decreased CDKN3 expression and E2F1 pathway inhibition, which could be rescued by treatment with an miR-127-3p inhibitor. CONCLUSION: Our data indicates, for the first time, an essential role for the circSDHC/miR-127-3p/CDKN3/E2F1 axis in RCC progression. Thus, circSDHC has potential to be a new therapeutic target in patients with RCC.

Long noncoding RNA-mRNA expression profiles and validation in pancreatic neuroendocrine neoplasms.

BACKGROUND: Pancreatic neuroendocrine neoplasms (pNENs) are a group of endocrine tumours arising in the pancreas and deemed to be the most common neuroendocrine tumours. The pathogenesis of pNENs remains unknown. Long noncoding RNAs (lncRNAs) are aberrantly expressed in cancers. The functional roles of lncRNAs and lncRNA-mRNA expression profiles in pNENs are undefined. The aim of this study was to identify the lncRNA and mRNA expression profiles and explore the lncRNA-mRNA co-expression networks associated with the pNENs carcinogenesis. METHOD: Differentially expressed lncRNA and mRNA in pNENs tissues from adjacent tissues were detected using human lncRNA microarray V3.0 containing 30 586 lncRNA and 26 109 coding transcripts. Probable functions for lncRNAs and mRNAs were predicted according to lncRNA-mRNA network. RESULTS: The microarray identified 2080 lncRNAs and 1771 mRNAs in pNENs tumours differentially expressed compared with the adjacent tissues. The GO terms and KEGG pathway annotation data indicated that cell projection morphogenesis, cell adhesion molecules pathway, PI3K-AKT signalling pathway, focal adhesion pathway, neuroactive ligand-receptor interaction pathways and Ras signalling pathways were significantly associated with the pNENs tumorigenesis. Co-expression network analysis revealed the differential interactions between lncRNAs and mRNAs in pNENs tumours and adjacent tissues. The genes, situated at the important nodes of the co-expression network, include ICOSLG, ENST00000512077, FGF8 and ENST00000511918. CONCLUSIONS: There were significant differences in lncRNA and mRNA expression between pNEN tumours and adjacent tissues, and these differences were associated with tumorigenesis through multiple biological processes and signalling pathways. These results provided important insights regarding lncRNA in pNENs pathogenesis and provide potential therapeutic targets.

Epithelial to mesenchymal transition is involved in ethanol promoted hepatocellular carcinoma cells metastasis and stemness.

Hepatocellular Carcinoma (HCC) is a malignant tumor with high rate of relapse and metastasis. Ethanol is a well-known risk factor for HCC; it promotes the progression and aggressiveness of HCC. However, the underlying mechanism remains unclear. In clinic studies, we showed that alcohol consumption is positively correlated with TNM stage and vessel invasion; HCC patients with chronic drinking history had faster progression rate and poorer prognosis compared to non-drinkers. In experimental models, ethanol exposure enhanced the metastasis, and invasion of HCC cells. Ethanol exposure increased cancer stem cells (CSC) population and enhanced stemness of HCC cells in vitro and in vivo. Mechanically, we found that ethanol exposure induced epithelial to mesenchymal transition (EMT) through activating Wnt/ß-catenin signaling pathway in HCC cells. We further demonstrated that ß-catenin siRNA or salinomycin (an inhibitor of Wnt/ß-catenin pathway) partially rescued ethanol-induced EMT. In conclusion, this study suggested that ethanol exposure promotes the metastasis and stemness of HCC cells by inducing EMT.

Risk factors and managements of hemorrhage associated with pancreatic fistula after pancreaticoduodenectomy.

BACKGROUND: Post-pancreaticoduodenectomy pancreatic fistula associated hemorrhage (PPFH) is one of the leading lethal complications. Our study was to analyze the risk factors and managements of hemorrhage associated with pancreatic fistula after pancreaticoduodenectomy, and to evaluate treatment options. METHOD: We analyzed 445 patients who underwent pancreaticoduodenectomy or pylorus-preserving pancreaticoduodenectomy and evaluated the relevance between clinical data and PPFH. RESULTS: The incidence of postoperative pancreatic fistula (POPF) was 27.42% (122/445), and the incidence of PPFH was 4.49% (20/445). Among the 20 patients with PPFH, 7 died and 13 were cured. Interventional angiographic therapy was performed for 10 patients and 5 were successfully treated. Relaparotomy was performed for 5 patients and 2 were successfully cured. Univariate logistic regression analysis indicated that several risk factors were related to PPFH: the nature of tumor (carcinoid/low-grade or high-grade malignancy), preoperative day 1 serum prealbumin, preoperative day 1 total bilirubin (TBIL), operative time, blood loss in the operation, operative method (vascular resection and revascularization), postoperative day 3 TBIL, biliary fistula, and the grade of POPF. The multivariate stepwise logistic regression analysis demonstrated that the nature of tumor and the grade of POPF were independently risk factors of PPFH. Receiver operating characteristic curve indicated that preoperative day 1 serum prealbumin level <173 mg/L and postoperative day 3 TBIL level ≥168 µmol/L were the risk factors of PPFH. CONCLUSIONS: The risk of PPFH was found to be increased with high potential malignancy and high grade of POPF. Angiography-embolization is one of the major and effective therapies for PPFH. Extraluminal-intraluminal PPFH is more serious and needs more aggressive treatments.

Surface-Engineered Polydopamine Particles as an Efficient Support for Catalytic Applications.

Mussel-inspired polydopamine (PDA) particles with the size of ∼270 nm are used as a support of palladium (Pd) nanoparticles (NPs) for catalyst preparation. The surface morphology of the PDA particle has been modified via corrosion of CF3COOH. Surface chemistry of the obtained PDA particle has been engineered by the formation of a carboxylic acid-terminated alkanethiol monolayer. The obtained self-assembled monolayer-modified PDA (SAM-PDA) particles are used to load Pd NPs by simply adding H2PdCl4 solution to a suspension of SAM-PDA particles at room temperature. Transmission electron microscopy, energy-dispersive X-ray mapping, dynamic light scattering, X-ray diffraction, X-ray photoelectron spectroscopy, UV-vis, and Fourier transform infrared are used to characterize the catalyst and to investigate the process. Uniform Pd NPs (2-3 nm) have been well-dispersed on the SAM-PDA particles via controllable surface engineering. Surface charges and interactions with a metal ion are regulated by the monolayer of carboxylic acids. The surface chemistry of PDA particles has been finely engineered for efficient loading of noble metal NPs. The obtained Pd/SAM-PDA catalyst has shown greatly increased activity and good reusability compared with Pd/PDA in the reduction of 4-nitrophenol (4-NP) by sodium borohydride or H2. The kinetic data of 4-NP hydrogenation catalyzed by Pd/SAM-PDA are fitted to a Langmuir-Hinshelwood (L-H) model, and the calculated apparent activation energy of this process is 40.77 kJ mol-1.

MiR-362-5p promotes the malignancy of chronic myelocytic leukaemia via down-regulation of GADD45α.

BACKGROUND: MicroRNAs (miR, miRNAs) play pivotal roles in numerous physiological and pathophysiological contexts. We investigated whether miR-362-5p act as an oncogene in chronic myeloid leukaemia (CML) and aimed to understand its potential underlying mechanisms. METHODS: We compared the miR-362-5p expression levels between CML and non-CML cell lines, and between fresh blood samples from CML patients and normal healthy controls using quantitative real-time PCR (qPCR). Cell counting kit-8 (CCK-8) and Annexin V-FITC/PI analyses were used to measure the effects of miR-362-5p on proliferation and apoptosis, and Transwell assays were used to evaluate migration and invasion. A xenograft model was used to examine in vivo tumourigenicity. The potential target of miR-362-5p was confirmed by a luciferase reporter assay, qPCR and western blotting. Involvement of the JNK1/2 and P38 pathways was investigated by western blotting. RESULTS: miR-362-5p was up-regulated in CML cell lines and fresh blood samples from CML patients, and was associated with Growth arrest and DNA damage-inducible (GADD)45α down-regulation. Inhibition of miR-362-5p simultaneously repressed tumour growth and up-regulated GADD45α expression in a xenograft model. Consistently, the knockdown of GADD45α expression partially neutralized the effects of miR-362-5p inhibition. Furthermore study suggested that GADD45α mediated downstream the effects of miR-362-5p, which might indirectly regulates the activation of the JNK1/2 and P38 signalling pathways. CONCLUSION: miR-362-5p acts as an oncomiR that down-regulates GADD45α, which consequently activates the JNK1/2 and P38 signalling. This finding provides novel insights into CML leukaemogenesis and may help identify new diagnostic and therapeutic targets.

Simulating the clinical manifestations and disease progression of human sepsis: A monobacterial injection approach for animal modeling.

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection, with great clinical heterogeneity, high morbidity, and high mortality. At the same time, there are many kinds of infection sources, the pathophysiology is very complex, and the pathogenesis has not been fully elucidated. An ideal animal model of sepsis can accurately simulate clinical sepsis and promote the development of sepsis-related pathogenesis, treatment methods, and prognosis. The existing sepsis model still uses the previous Sepsis 2.0 modelling standard, which has some problems, such as many kinds of infection sources, poor repeatability, inability to take into account single-factor studies, and large differences from clinical sepsis patients. To solve these problems, this study established a new animal model of sepsis. The model uses intravenous tail injection of a single bacterial strain, simplifying the complexity of multibacterial infection, and effectively solving the above problems.

Epidemiological and genetic characteristics of norovirus in Hangzhou, China, in the postepidemic era.

OBJECTIVE: Norovirus (NoV) is an important human pathogen that can cause severe gastroenteritis in vulnerable populations. This study aimed to analyze the epidemiological and genetic characteristics of 2021-2023 NoV in Hangzhou, China. METHODS: This study enrolled patients aged 0-18 years who underwent NoV RNA detection in the hospital between January 2021 and October 2023 and analyzed the epidemiological characteristics of NoV. Polymerase chain reaction (PCR) was used to detect NoV RNA. Subtype classification and whole-genome sequencing were performed. RESULTS: There was a high prevalence of NoV infection in 2023, with NoV-positive samples accounting for 63.10 % of the total number of positive samples collected during the three-year period. The prevalence was abnormally high in summer, and the number of positive samples accounted for 48.20 % of the total positive samples for the whole year, which was much greater than the level in the same period in previous years (2023, 48.20% vs 2021, 13.66% vs 2022, 15.21 %). The GⅡ.4 subtype played a leading role, followed by increased mixed infection with GⅠ.5 and GⅡ.4. Whole-genome sequencing results suggested that GII.P16-GⅡ.4 had R297H and D372N key locus mutations. The evolutionary rate was 4.29 × 10-3 for the RdRp gene and 4.84 × 10-3 for the VP1 gene. The RdRp gene and VP1 gene of NoV GII.P16-GⅡ.4 have undergone rapid population evolution during the COVID-19 epidemic. CONCLUSION: In the summer of 2023, an abnormally high incidence of NoV appeared in Hangzhou, China. The major epidemic strain GII.P16-GⅡ.4 showed a certain range of gene mutations and a fast evolutionary rate.

Pirfenidone ameliorates alcohol-induced promotion of breast cancer in mice.

Purpose: Alcohol consumption increases the risk of breast cancer and promotes cancer progression. Alcohol exposure could affect both processes of the mammary carcinogenesis, namely, the cell transformation and onset of tumorigenesis as well as cancer aggressiveness including metastasis and drug resistance/recurrence. However, the cellular and molecular mechanisms underlying alcohol tumor promotion remain unclear. There are four members of the mammalian p38 mitogen-activated protein kinase (MAPK) family, namely, p38α, p38ß, p38γ and p38δ. We have previously demonstrated alcohol exposure selectively activated p38γ MAPK in breast cancer cells in vitro and in vivo. Pirfenidone (PFD), an antifibrotic compound approved for the treatment of idiopathic pulmonary fibrosis, is also a pharmacological inhibitor of p38γ MAPK. This study aimed to determine whether PFD is useful to inhibit alcohol-induced promotion of breast cancer. Methods: Female adolescent (5 weeks) MMTV-Wnt1 mice were exposed to alcohol with a liquid diet containing 6.7% ethanol. Some mice received intraperitoneal (IP) injection of PFD (100 mg/kg) every other day. After that, the effects of alcohol and PFD on mammary tumorigenesis and metastasis were examined. Results: Alcohol promoted the progression of mammary tumors in adolescent MMTV-Wnt1 mice. Treatment of PFD blocked tumor growth and alcohol-promoted metastasis. It also significantly inhibited alcohol-induced tumorsphere formation and cancer stem cell (CSC) population. Conclusion: PFD inhibited mammary tumor growth and alcohol-promoted metastasis. Since PFD is an FDA-approved drug, the current findings may be helpful to re-purpose its application in treating aggressive breast cancer and alcohol-promoted mammary tumor progression.

Deciphering and designing microbial communities by genome-scale metabolic modelling.

Microbial communities are shaped by the complex interactions among organisms and the environment. Genome-scale metabolic models (GEMs) can provide deeper insights into the complexity and ecological properties of various microbial communities, revealing their intricate interactions. Many researchers have modified GEMs for the microbial communities based on specific needs. Thus, GEMs need to be comprehensively summarized to better understand the trends in their development. In this review, we summarized the key developments in deciphering and designing microbial communities using different GEMs. A timeline of selected highlights in GEMs indicated that this area is evolving from the single-strain level to the microbial community level. Then, we outlined a framework for constructing GEMs of microbial communities. We also summarized the models and resources of static and dynamic community-level GEMs. We focused on the role of external environmental and intracellular resources in shaping the assembly of microbial communities. Finally, we discussed the key challenges and future directions of GEMs, focusing on the integration of GEMs with quorum sensing mechanisms, microbial ecology interactions, machine learning algorithms, and automatic modeling, all of which contribute to consortia-based applications in different fields.