Genomic investigation and nationwide tracking of pediatric invasive nontyphoidal Salmonella in China.

Invasive nontyphoidal Salmonella (iNTS) causes significant concern with ~15% morbidity, affecting populations mainly in African countries. However, iNTS infections among the Chinese pediatric population remain largely unknown. Here, we conducted a genomic investigation to study pediatric iNTS infections in a Chinese hospital. iNTS isolates accounted for 15.2% (18/119) of all nontyphoidal Salmonella (NTS) strains. Compared to non-iNTS isolates, iNTS isolates harbored a lower prevalence of antimicrobial-resistant genes of fluoroquinolones and ß-lactams, as well as disinfectant determinants and plasmids, but carried a significantly higher prevalence of cdtB, faeCDE, and tcpC genes. Importantly, we detected an emerging serovar Goldcoast as the predominant iNTS serovar locally. By integrating 320 global Goldcoast genomes based on the One Health samplings, we conducted nationwide phylogenomic tracking and detected repeated human-to-human transmission events among iNTS cases caused by an underestimated serovar Goldcoast. Together, our exploratory genomic approach highlights a new trend in pediatric iNTS infections.

Integrating single-cell and spatial analysis reveals MUC1-mediated cellular crosstalk in mucinous colorectal adenocarcinoma.

BACKGROUND: Mucinous colorectal adenocarcinoma (MCA) is a distinct subtype of colorectal cancer (CRC) with the most aggressive pattern, but effective treatment of MCA remains a challenge due to its vague pathological characteristics. An in-depth understanding of transcriptional dynamics at the cellular level is critical for developing specialised MCA treatment strategies. METHODS: We integrated single-cell RNA sequencing and spatial transcriptomics data to systematically profile the MCA tumor microenvironment (TME), particularly the interactome of stromal and immune cells. In addition, a three-dimensional bioprinting technique, canonical ex vivo co-culture system, and immunofluorescence staining were further applied to validate the cellular communication networks within the TME. RESULTS: This study identified the crucial intercellular interactions that engaged in MCA pathogenesis. We found the increased infiltration of FGF7+/THBS1+ myofibroblasts in MCA tissues with decreased expression of genes associated with leukocyte-mediated immunity and T cell activation, suggesting a crucial role of these cells in regulating the immunosuppressive TME. In addition, MS4A4A+ macrophages that exhibit M2-phenotype were enriched in the tumoral niche and high expression of MS4A4A+ was associated with poor prognosis in the cohort data. The ligand-receptor-based intercellular communication analysis revealed the tight interaction of MUC1+ malignant cells and ZEB1+ endothelial cells, providing mechanistic information for MCA angiogenesis and molecular targets for subsequent translational applications. CONCLUSIONS: Our study provides novel insights into communications among tumour cells with stromal and immune cells that are significantly enriched in the TME during MCA progression, presenting potential prognostic biomarkers and therapeutic strategies for MCA. KEY POINTS: Tumour microenvironment profiling of MCA is developed. MUC1+ tumour cells interplay with FGF7+/THBS1+ myofibroblasts to promote MCA development. MS4A4A+ macrophages exhibit M2 phenotype in MCA. ZEB1+ endotheliocytes engage in EndMT process in MCA.

Identifying the Crucial Biomarker of MASH-Related HCC.

OBJECTIVES: This study aimed to explore the key oncogenic factor of metabolicassociated steatohepatitis (MASH) to hepatocellular carcinoma (HCC). METHODS: We utilized four differential GEO datasets (GSE164760, GSE139602, GSE197112, and GSE49541) to identify the key oncogenic factor for MASH-related HCC. The differential genes were analyzed using the GEO2R algorithm online. The GEPIA online website was used to explore the expression of selected four genes (SPP1, GNMT, CLDN11, and THBS2). The genetic alterations in genes were estimated by the cBioPortal website. The Kaplan-Meier Plotter online database was applied to explore the prognostic value of SPP1. Univariate and multivariate Cox analyses were carried out to further confirm the prognostic value of SPP1. The GO and KEGG enrichment analysis exported associated pathways with SPP1 expression. The positively or negatively related immune cells and immune checkpoint expressions were identified through Pearson correlation analysis. The lipogenesis-associated proteins were detected using western blotting and fluorescence. The high-fat diet (HFD) mouse model was constructed, and liver samples were collected. RESULTS: SPP1, GNMT, CLDN11, and THBS2 were determined in the transformation process of MASH to liver fibrosis. SPP1 and GNMT were upregulated in the HCC tumor tissue. SPP1, in particular, had the potential to be the prognostic factor through Cox analysis. Remarkably, SPP1 was highly expressed in HCC compared to normal tissues in three independent datasets (GSE121248, GSE14520, and GSE45267). SPP1 is mainly involved in the amplification and deep deletion mutations. SPP1 was found to be strongly correlated with ANXA2 expression, and ANXA2 was also highly expressed in HCC with significant prognostic performance. Moreover, SPP1 was found to participate in the carcinogenic mechanism and correlate with immune cells and immune checkpoint expression. SPP1 knockdown suppressed the SREBP1 and FASN expressions and increased the SIRT1 expression in vitro. Moreover, the HFD model validated the upregulation of SPP1 in the fatty liver in vivo. CONCLUSION: SPP1 may be the key oncogenic factor for the transformation of MASH to HCC, and it could be a potential immunotherapeutic target in HCC.

Preparation of Lanthanum-Modified Tea Waste Biochar and Its Adsorption Performance on Fluoride in Water.

In this study, tea waste was used as a raw material, and TBC (tea waste biochar) was prepared by pyrolysis at 700 °C. La(NO3)3·6H2O was used as the modifier to optimize one-way modification; the orthogonal experiment was undertaken to determine the optimal preparation conditions; and La-TBC (lanthanum-modified biochar) was obtained. The key factors for the adsorption of fluoride by La-TBC were investigated by means of batch adsorption experiments, and kinetics and isothermal adsorption experiments were carried out on the adsorption of fluoride in geothermal hot spring water. The adsorption mechanism of fluoride by La-TBC was analyzed via characterization methods such as SEM-EDS (Scanning Electron Microscope and Energy Dispersive Spectrometer), BET (Brunauer-Emmett-Teller), FTIR (Fourier transform infrared), XRD (X-ray diffraction), and so on. The results show that La-TBC had the best adsorption effect on fluoride at pH 7. The process of adsorption of fluoride follows the pseudo-second-order kinetics and Langmuir isothermal model, and the maximum theoretical adsorption quantity was 47.47 mg/g at 80 °C, while the removal rate of fluoride from the actual geothermal hot spring water reached more than 95%. The adsorption process was dominated by the monolayer adsorption of chemicals, and the mechanisms mainly include pore filling, ion exchange, and electrostatic interaction.

Unlocking hepatocellular carcinoma aggression: STAMBPL1-mediated TRAF2 deubiquitination activates WNT/PI3K/NF-kb signaling pathway.

STAM Binding Protein Like 1 (STAMBPL1), functions as a deubiquitinase (DUB) and plays a significant role in various types of cancers. However, its effect as a DUB participating in the HCC tumorigenesis and progression still unknown. In the study, the upregulation and strong prognosis value of STAMBPL1 were identified in HCC patients. Functionally, STAMBPL1 significantly promoted HCC cells proliferation and metastasis, and it interacts with TRAF2 and stabilize it via the deubiquitination at the K63 residue. The TRAF2 upregulation stabilized by STAMBPL1 overexpression transfers of P65 protein into the nucleus and activates the WNT/PI3K/ NF-kb signaling pathway. The 251-436 sites of STAMBPL1 particularly interact with the 294-496 sites of TRAF2, thereby exerting the function of DUB and removing the ubiquitin molecules attached to TRAF2. Our research unveiled a new function of STAMBPL1 in mediating TRAF2 deubiquitination and stabilization, thereby activating the WNT/PI3K/NF-kb signaling pathway, suggesting its potential as a novel biomarker and therapeutic target for HCC.

Microbiological hazards in infant and toddler food in China: A comprehensive study between 2004 and 2022.

Infant and toddler food (ITF), including powdered infant and follow-up formula (PIFF) and complementary food (CF), provides the majority of early-life nutrients for young children. As infants and toddlers are more vulnerable to foodborne diseases, the safety concern of ITF is the ultimate priority. However, nationwide surveillance for the presence of hazards, specifically microbiological hazards, in the Chinese ITF is partially known, posing a significant knowledge gap for risk ranking. Most importantly, the related regional surveys were largely published in Chinese, making the data unavailable for global sharing. To bridge these gaps, we screened 5,306 publications and conducted a comprehensive meta-analysis for microbiological hazards using 129 qualified studies. The four most reported microbiological hazards in ITF were Bacillus cereus (13.4 %), Cronobacter (4.8 %), Staphylococcus aureus (1.3 %), and Salmonella (1.1 %). B. cereus is a risk factor in ITF, specifically in PIFF, cereals, and ready-to-eat food. The prevalence of B. cereus was high in Northern and Southern China, while the prevalence of Cronobacter was high in Central China. Cronobacter is a microbiological hazard, specifically in PIFF, with a prevalence of 3.0 %. Interestingly, the prevalence dynamics of Cronobacter and B. cereus in ITF were rising and stable, respectively, whereas the prevalence of S. aureus and Salmonella decreased over time. Together, our analysis will promote the global sharing of these critical findings and may guide future policy making.

Salmonellosis outbreak archive in China: data collection and assembly.

Infectious disease outbreaks transcend the medical and public health realms, triggering widespread panic and impeding socio-economic development. Considering that self-limiting diarrhoea of sporadic cases is usually underreported, the Salmonella outbreak (SO) study offers a unique opportunity for source tracing, spatiotemporal correlation, and outbreak prediction. To summarize the pattern of SO and estimate observational epidemiological indicators, 1,134 qualitative reports screened from 1949 to 2023 were included in the systematic review dataset, which contained a 506-study meta-analysis dataset. In addition to the dataset comprising over 50 columns with a total of 46,494 entries eligible for inclusion in systematic reviews or input into prediction models, we also provide initial literature collection datasets and datasets containing socio-economic and climate information for relevant regions. This study has a broad impact on advancing knowledge regarding epidemic trends and prevention priorities in diverse salmonellosis outbreaks and guiding rational policy-making or predictive modeling to mitigate the infringement upon the right to life imposed by significant epidemics.

Ferrostatin-1 inhibits ferroptosis of vascular smooth muscle cells and alleviates abdominal aortic aneurysm formation through activating the SLC7A11/GPX4 axis.

Ferroptosis, a type of iron-catalyzed necrosis, is responsible for vascular smooth muscle cell (VSMC) death and serves as a potential therapeutic target for alleviating aortic aneurysm. Here, our study explored the underlying mechanism of ferroptosis affecting VSMC functions and the resultant formation of AAA using its inhibitor Ferrostatin-1 (Fer-1). Microarray-based gene expression profiling was employed to identify differentially expressed genes related to AAA and ferroptosis. An AAA model was established by angiotensin II (Ang II) induction in apolipoprotein E-knockout (ApoE-/- ) mice, followed by injection of Fer-1 and RSL-3 (ferroptosis inducer). Then, the role of Fer-1 and RSL-3 in the ferroptosis of VSMCs and AAA formation was analyzed in Ang II-induced mice. Primary mouse VSMCs were cultured in vitro and treated with Ang II, Fer-1, sh-SLC7A11, or sh-GPX4 to assess the effect of Fer-1 via the SLC7A11/GPX axis. Bioinformatics analysis revealed that GPX4 was involved in the fibrosis formation of AAA, and there was an interaction between SLC7A11 and GPX4. In vitro assays showed that Fer-1 alleviated Ang II-induced ferroptosis of VSMCs and retard the consequent AAA formation. The mechanism was associated with activation of the SLC7A11/GPX4 pathway. Silencing of SLC7A11 or GPX4 could inhibit the ameliorating effect of Fer-1 on the ferroptosis of VSMCs. In vivo animal studies further demonstrated that Fer-1 inhibited Ang II-induced ferroptosis and vessel wall structural abnormalities in AAA mouse through activation of the SLC7A11/GPX4 pathway. Fer-1 may prevent AAA formation through activation of the SLC7A11/GPX4 pathway.

Evaluation of mismatch-repair and microsatellite-instability status in a Chinese colorectal cancer Cohort.

BACKGROUND: Immunohistochemistry (IHC) and traditional polymerase chain reaction (PCR) are the methods of choice in clinical practice to identify the mismatch repair (MMR) and microsatellite instability (MSI) status in colorectal cancer (CRC). In some previous researches, the concordance rate between two methods was different and discordance existed in about 1 %-9.7 %. METHODS: We retrospectively reviewed 406 patients received surgical CRC resections and tests of both MMR IHC and MSI PCR from January 2019 to April 2022 in Shanghai Changzheng Hospital. The incidence of deficient mismatch repair (dMMR) or microsatellite instability-high (MSI-H) CRCs, the concordance rate between two methods, and the reasons for discordant results were evaluated with clinicopathological data, immunochemical staining, whole-exome sequencing, and MLH1 methylation analysis. RESULTS: Among 406 patients, the incidence of MSI-H CRCs was 7.88 %. Nearly a quarter of the cases under reexamination of IHC was initial misinterpreted. Besides, the concordance rate between MMR IHC and MSI PCR was 99.26 % (401 of 404) and the Kappa value was 0.945 (p < 0.001). Finally, some somatic variants of MMR and POLE genes which may explain the discordance were identified. CONCLUSION: The incidence rate of MSI-H in Chinese patients with CRC might be relatively low owing to tumor location. Although MSI and IHC analyses are highly concordant, both MMR IHC and MSI PCR tests should be simultaneously performed and MMR IHC should be interpreted by experienced pathologists. In the future, further studies on discordant results should be carried out to improve the personalized management of CRC.

Mobilome-driven partitions of the resistome in Salmonella.

IMPORTANCE: Antimicrobial resistance (AMR) has become a significant global challenge, with an estimated 10 million deaths annually by 2050. The emergence of AMR is mainly attributed to mobile genetic elements (MGEs or mobilomes), which accelerate wide dissemination among pathogens. The interaction between mobilomes and AMR genes (or resistomes) in Salmonella, a primary cause of diarrheal diseases that results in over 90 million cases annually, remains poorly understood. The available fragmented or incomplete genomes remain a significant limitation in investigating the relationship between AMR and MGEs. Here, we collected the most extensive closed Salmonella genomes (n = 1,817) from various sources across 58 countries. Notably, our results demonstrate that resistome transmission between Salmonella lineages follows a specific pattern of MGEs and is influenced by external drivers, including certain socioeconomic factors. Therefore, targeted interventions are urgently needed to mitigate the catastrophic consequences of Salmonella AMR.

Awareness of HBV Functional Cure and Attitude Toward Related Clinical Trials Among Patients with Chronic Hepatitis B in China.

Purpose: HBV functional cure is an optimal treatment goal for chronic hepatitis B (CHB) at present and numerous new drugs aiming for HBV functional cure are in development. We carried out an internet-based survey to understand the treatment status, unmet needs, awareness of HBV functional cure and attitude toward related clinical trials among CHB patients in China. Patients and Methods: An internet-based anonymous survey was conducted on CHB patients who reside in mainland China. Determinants of awareness and attitude were identified by logistic regression models. Results: Of the 1220 CHB patients who completed the survey questionnaire, 11.1% (135/1220) were aware of HBV functional cure and 50.2% (612/1220) answered "definitely will" to participate in related clinical trials. Participants who knew their HBsAg level (HBsAg<1500 IU/mL: OR=3.03, 95% CI: 1.87-4.92; HBsAg≥1500 IU/mL: OR=2.57, 95% CI: 1.35-4.88), who expected to achieve HBsAg loss with treatment (OR=1.63, 95% CI: 1.07-2.50) and who were dissatisfied with current treatment due to the failure of achieving HBsAg loss (OR=1.67, 95% CI: 1.10-2.53) had better awareness of HBV functional cure. Participants who had HBsAg level less than 1500 IU/mL (OR=1.45, 95% CI: 1.05-1.99), treatment with pegylated interferon alpha with or without nucleos(t)ide (OR=1.68, 95% CI: 1.11-2.53) and better awareness of HBV functional cure (OR=1.62, 95% CI: 1.01-2.61) were more likely to say "definitely will" to participate in related clinical trials. Conclusion: Chinese CHB patients reported a low awareness of HBV functional cure. Although CHB patients in China reported a low rate of HBV functional cure awareness, they had a high acceptance of related clinical trials.

A comparison of behavioral paradigms assessing spatial memory in tree shrews.

Impairments in spatial navigation in humans can be preclinical signs of Alzheimer's disease. Therefore, cognitive tests that monitor deficits in spatial memory play a crucial role in evaluating animal models with early stage Alzheimer's disease. While Chinese tree shrews (Tupaia belangeri) possess many features suitable for Alzheimer's disease modeling, behavioral tests for assessing spatial cognition in this species are lacking. Here, we established reward-based paradigms using the radial-arm maze and cheeseboard maze for tree shrews, and tested spatial memory in a group of 12 adult males in both tasks, along with a control water maze test, before and after bilateral lesions to the hippocampus, the brain region essential for spatial navigation. Tree shrews memorized target positions during training, and task performance improved gradually until reaching a plateau in all 3 mazes. However, spatial learning was compromised post-lesion in the 2 newly developed tasks, whereas memory retrieval was impaired in the water maze task. These results indicate that the cheeseboard task effectively detects impairments in spatial memory and holds potential for monitoring progressive cognitive decline in aged or genetically modified tree shrews that develop Alzheimer's disease-like symptoms. This study may facilitate the utilization of tree shrew models in Alzheimer's disease research.