bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Tanreqing injection on the gut microbiota in healthy volunteers
Authors: Li Shiyu , Zhang Wenxia , Liu Sijie , Zhou Yichen , Liu Wei , Yuan Weian , He Min 
Published: October 2024

ObjectivesMany studies have confirmed that antibacterial agents can disrupt the human gut microbiota. In China, Tanreqing injection (TRQ) is a drug with antibacterial activity that is widely used in the treatment of respiratory infections. However, its specific influence on gut microbiota remains unclear. This study aimed to investigate the effect of TRQ on the gut microbiota of healthy volunteers.MethodsTwelve healthy adults received 20 ml of TRQ intravenously daily for 7 consecutive days. At six timepoints (Pre, on D1, D3, D5, D7 and follow-up visit) fecal samples were collected and analyzed using 16S rRNA gene sequencing.ResultsEleven people were included in the analysis finally. TRQ did not significantly alter gut microbiota diversity or richness (Shannon and Simpson and Chao1 index) in healthy people during the intervention. Gut microbial structure was stable (weighted and unweighted Unifrac). Using a machine learning method based on PLS-DA analysis, the separation trend on D7 at the genus level was found, returning to baseline two days after discontinuation. The abundance of major genus fluctuated on D7 compared with that prior to treatment, including an increase of unclassified_f_Enterobacteriaceae (13.0611%), a decrease of Bifidobacterium and Escherichia-Shigella (6.887%, 10.487%). Functional prediction analysis did not reveal any significant difference.ConclusionsOur study showed short-term use of TRQ at conventional doses may not cause perturbations to the gut microbiota in healthy adults. This finding provides some useful information for the safe use of TRQ in the treatment of respiratory infections.Clinical trial registrationhttps://www.medicalresearch.org.cn/, identifier MR-31-24-014367.
Association of glycerolipid metabolism with gut microbiota disturbances in a hamster model of high-fat diet-induced hyperlipidemia
Authors: Han Lijie , Hu Chaowei , Du Zhiyong , Yu Huahui , Du Yunhui , Li Linyi , Li Fan , Wang Yu , Gao Xiaoqian , Sun Xuechun , Zhang Zihan , Qin Yanwen 
Published: October 2024

BackgroundHigh-fat diet (HFD)-induced hyperlipidemia, which is associated with gut microbiota disturbances, remains a major public health challenge. Glycerolipid metabolism is responsible for lipid synthesis and is thus involved in the development of hyperlipidemia. However, possible association between the HFD-modulated gut microbiome and the glycerolipid metabolism pathway remains unclear.MethodsHamsters were fed a HFD for 4 weeks to establish a hyperlipidemia model. Fecal, plasma and liver samples collected from hamsters fed a HFD or a normal chow diet (NCD) were used for integrative metagenomic and untargeted metabolomic analyses to explore changes in the composition and functions of the gut microbiota, and relevant metabolites. Spearman rank correlation analysis was used to explore correlations between gut microbes and circulating glycerolipid metabolites, gut microbes and lipids, and circulating glycerolipid metabolites and lipids.ResultsThe gut microbial composition of HFD hamsters showed significant alterations at the phylum, genus, and species levels that were skewed toward metabolic disorders compared with that of NCD hamsters. Functional characterization by KEGG analysis identified enrichment of the glycerolipid metabolism pathway in the gut microbiome of HFD hamsters. Plasma and liver metabolomics further indicated the upregulation and enrichment of glycerolipid metabolites in HFD hamsters. The Faecalibaculum, Allobaculum, and Eubacterium genera were positively correlated with plasma glycerolipid metabolites and lipid indices.ConclusionThe findings of this study suggest an association between glycerolipid metabolism and the HFD-modulated gut microbiome that is involved in the development of hyperlipidemia.
Calorie restriction during gestation impacts maternal and offspring fecal microbiome in mice
Authors: Gilley Stephanie P. , Ruebel Meghan L. , Chintapalli Sree V. , Wright Clyde J. , Rozance Paul J. , Shankar Kartik 
Published: October 2024

BackgroundMaternal undernutrition is the most common cause of fetal growth restriction (FGR) worldwide. FGR increases morbidity and mortality during infancy, as well as contributes to adult-onset diseases including obesity and type 2 diabetes. The role of the maternal or offspring microbiome in growth outcomes following FGR is not well understood.MethodsFGR was induced by 30% maternal calorie restriction (CR) during the second half of gestation in C57BL/6 mice. Pup weights were obtained on day of life 0, 1, and 7 and ages 3, 4 and 16 weeks. Fecal pellets were collected from pregnant dams at gestational day 18.5 and from offspring at ages 3 and 4 weeks of age. Bacterial genomic DNA was used for amplification of the V4 variable region of the 16S rRNA gene. Multivariable associations between maternal CR and taxonomic abundance were assessed using the MaAsLin2 package. Associations between microbial taxa and offspring outcomes were performed using distance-based redundancy analysis and Pearson correlations.ResultsFGR pups weighed about 20% less than controls. Beta but not alpha diversity differed between control and CR dam microbiomes. CR dams had lower relative abundance of Turicibacter, Flexispira, and Rikenella, and increased relative abundance of Parabacteroides and Prevotella. Control and FGR offspring microbiota differed by beta diversity at ages 3 and 4 weeks. At 3 weeks, FGR offspring had decreased relative abundance of Akkermansia and Sutterella and increased relative abundance of Anaerostipes and Paraprevotella. At 4 weeks, FGR animals had decreased relative abundance of Allobaculum, Sutterella, Bifidobacterium, and Lactobacillus, among others, and increased relative abundance of Turcibacter, Dorea, and Roseburia. Maternal Helicobacter abundance was positively associated with offspring weight. Akkermansia abundance at age 3 and 4 weeks was negatively associated with adult weight.ConclusionsWe demonstrate gut microbial dysbiosis in pregnant dams and offspring at two timepoints following maternal calorie restriction. Additional research is needed to test for functional roles of the microbiome in offspring growth outcomes.
Causal association between thyroid function and the risk of infertility: a Mendelian randomization study
Authors: Liu Qinyu , Qiu Yingkun , Jiang Jialin , Long Shushu , Zhu Chengyu , Chen Gang , Wen Junping 
Published: October 2024

ObjectivesThyroid dysfunction is commonly associated with the risk of infertility in both females and males. However, recent randomized controlled trials have demonstrated that thyroid function levels in females are not significantly related to infertility, and evidence on the association between male thyroid function and infertility is limited. We aim to investigate the association between thyroid function levels and infertility in both females and males.MethodA two-sample Mendelian randomization study was conducted using four methods, with the inverse variance weighted method (IVW) as the primary approach. Data on thyroid function as the exposure were obtained from the ThyroidOmics Consortium and UK Biobank, including over 700,000 individuals from a large meta-analysis of genome-wide association studies for thyroid function and dysfunction. The outcome data for infertility in both sex encompassed more than 70,000 individuals from the FinnGen Consortium. All participants were adults of European ancestry. The MR Egger regression intercept and Cochran’s Q test were employed to evaluate directional pleiotropy and heterogeneity.ResultsThe results indicated no causal effect of thyroid-stimulating hormone (TSH) and free tetraiodothyronine (fT4) on female and male infertility. Furthermore, no causal association between hypo- and hyperthyroidism and infertility were identified. Notably, we observed a causal relationship between high TSH and endometriosis-related infertility (OR=0.82, 95% CI: 0.74–0.91, P = 1.49E-04).ConclusionsThis study did not find evidence for casual relationship between thyroid function levels and risk of infertility. The findings suggest that overall thyroid function levels may not be a significant predictor of infertility risk.
Predictive factors of response to liraglutide in patients with type 2 diabetes mellitus and metabolic syndrome
Authors: Song Jinfang , Li Na , Zhuang Yongru , Chen Ya , Zhang Chu , Zhu Jian 
Published: October 2024

BackgroundAlthough liraglutide has established advantages in treating patients with type 2 diabetes mellitus (T2DM) and metabolic syndrome (MS), there are still some patients with lower responsiveness to liraglutide. The objective of the study was to identify the predictors of response to liraglutide in patients with T2DM and MS.MethodsThis retrospective cohort study included patients diagnosed with T2DM and MS who received liraglutide treatment as a part of their diabetes management for a minimum of six months. The participants were stratified into two groups: responders (HbA1c reduction≥1.0% and weight loss≥3%) and non-responders. The discrepancies in baseline data between the two groups were analyzed, containing comedications, test parameters, and basic profiles. The affecting factors of response to liraglutide by Logistic regression analysis were performed, and the predictive ability of the identified factors was evaluated by plotting a receiver operating characteristic (ROC) curve.ResultsA total of 417 patients with T2DM and MS were examined and followed up according to the inclusion criteria, and 206 patients completed the follow-up; 105 (50.97%) were responders and 101 (49.03%) were non-responders to liraglutide. The binary logistic regression analysis identified baseline HbA1c, baseline BMI, and the duration of T2DM as significant predictors of glycemic and weight responses to liraglutide (P &lt;0.05). The area under the curve of the ROC for the three predictors of liraglutide response after 6 months of treatment was 0.851 (95% confidence interval: 0.793 - 0.910).ConclusionThe baseline HbA1c, baseline BMI, and duration of T2DM were shown to be predictive factors of glycemic and weight improvements in patients with T2DM and MS treated with liraglutide, and had good predictive power.
Systemic increase in IL-26 is associated with severe COVID-19 and comorbid obstructive lung disease
Authors: Cardenas Eduardo I. , Robertson Josefina , Misaghian Salvia , Brown Jermaine , Wang Mingyue , Stengelin Martin , Sigal George , Wohlstadter Jacob , Gisslén Magnus , Lindén Anders 
Published: October 2024

BackgroundIL-26 is a key mediator of pulmonary host defense given its abundant expression in human airways and its established antibacterial properties. Moreover, recent studies indicate that IL-26 can also inhibit viral replication. Along these lines, we have previously reported an increase in the plasma concentration of IL-26 among patients with acute COVID-19 that is linked to harmful hyperinflammation. Nevertheless, it is still unclear whether this systemic increase in IL-26 relates to disease severity, sex, comorbidities, viral load, or the innate immune response in acute COVID-19.MethodsIL-26 was quantified using ELISA in plasma samples from a large cohort of well-characterized patients with acute COVID-19 (n=178) and healthy controls (n=30). The plasma concentrations of SARS-CoV-2 nucleocapsid and spike protein, as well as those of IFN-α2a, IFN-β, and IFN-γ, were determined using electrochemiluminescence immunoassay. The concentration of double-stranded DNA was determined using fluorometry.ResultsThe plasma concentration of IL-26 was increased in patients with severe/critical COVID-19, particularly among males and patients with comorbid obstructive lung disease. Moreover, the concentration of IL-26 displayed positive correlations with length of hospital stay, as well as with systemic markers of viral load, antiviral immunity, and extracellular DNA.ConclusionsSystemic IL-26 is involved in severe COVID-19, especially in males and patients with comorbid obstructive lung disease. These findings argue that systemic IL-26 has pathogenic and antiviral relevance, as well as biomarker potential.
Integrated transcriptome analysis of CSE1L regarding poor prognosis and immune infiltration in bladder urothelial carcinoma and experimental verification
Authors: Liu Runze , Ma Jiayi , Zhang Yong , Zhou Zhongbao 
Published: October 2024

BackgroundBladder urothelial carcinoma (BLCA) is one of the most prevalent tumors globally, with its incidence rising notably in developed countries, significantly affecting human health. CSE1L encodes a protein that is involved in various cellular processes and plays a critical role in cancer initiation and progression. However, its role in BLCA remains underexplored.MethodsCSE1L expression in BLCA was analyzed using TCGA data and validated by qRT-PCR and Western blot in clinical samples. Survival analysis and Cox regression models were used to evaluate its prognostic value. Functional enrichment and protein interaction analyses were performed, and immune cell infiltration was assessed using CIBERSORT. Drug sensitivity was analyzed using GDSC data. In vitro assays evaluated the effects of CSE1L knockdown on cell proliferation, migration, and invasion.ResultsCSE1L was found to be significantly overexpressed in BLCA tissues compared to normal tissues. High CSE1L expression was associated with poor overall survival and unfavorable clinicopathological features. Functional enrichment analysis revealed that DEGs related to CSE1L were involved in cell cycle regulation and immune-related pathways. Immune infiltration analysis indicated a significant correlation between CSE1L expression and various immune cell types, particularly T cells and macrophages. Drug sensitivity analysis identified several chemotherapeutic agents, including MG-132, Palbociclib, and Nutlin-3a, which were more effective in the low-CSE1L expression group, while the high-CSE1L expression group showed sensitivity to drugs like S-Trityl-L-cysteine, Bleomycin, and Cisplatin. In vitro knockdown of CSE1L in BLCA cell lines inhibited cell proliferation, migration, and invasion.ConclusionsThe overexpression of CSE1L is associated with the progression and poor prognosis of bladder cancer, suggesting it could be a promising target for bladder cancer in the future.
Unraveling the ecological landscape of mast cells in esophageal cancer through single-cell RNA sequencing
Authors: Zhang Shengyi , Zhang Xinyi , Xiahou Zhikai , Zuo Shunqing , Xue Jialong , Zhang Yi 
Published: October 2024

BackgroundEsophageal cancer (EC) is a major health issue, ranking seventh in incidence and sixth in mortality worldwide. Despite advancements in multidisciplinary treatment approaches, the 5-year survival rate for EC remains low at 21%. Challenges in EC treatment arise from late-stage diagnosis, high malignancy, and poor prognosis. Understanding the tumor microenvironment is critical, as it includes various cellular and extracellular components that influence tumor behavior and treatment response. Mast cells (MCs), as tissue-resident immune cells, play dual roles in tumor dynamics. High-throughput single-cell RNA sequencing offers a powerful tool for analyzing tumor heterogeneity and immune interactions, although its application in EC is limited.MethodsIn this study, we investigated the immune microenvironment of EC using single-cell RNA sequencing and established a comprehensive immune profile. We also performed analysis of upstream transcription factors and downstream pathway enrichment to further comprehensively decipher MCs in EC. Besides, we performed knockdown experiments to explore the role of epidermal growth factor receptor (EGFR) signaling pathway in MCs-tumor cell interactions, highlighting its potential as a prognostic marker. Finally, we constructed a prognostic model for EC, which provided valuable suggestions for the diagnosis and prognosis of EC.ResultsOur analysis identified 11 major cell types, of which MCs were particularly present in pericarcinoma tissues. Further grouping of the 5,001 MCs identified 8 distinct subtypes, including SRSF7-highly expressed MCs, which showed strong tumor preference and potential tumor-promoting properties. Moreover, we identified the key signaling receptor EGFR and validated it by in vitro knockdown experiments, demonstrating its cancer-promoting effects. In addition, we established an independent prognostic indicator, SRSF7+ MCs risk score (SMRS), which showed a correlation between high SMRS group and poor prognosis.ConclusionThese findings illuminate the complex interactions within the tumor microenvironment of EC and suggest that targeting specific MCs subtypes, particularly via the EGFR signaling pathway, may present novel therapeutic strategies. This study establishes a comprehensive immune map of EC, offering insights for improved treatment approaches.
Assessing lobster and co-predator feeding rates on barrens-forming sea urchins in South East Australia
Authors: Day Jeremy K. , Knott Nathan A. , Swadling Daniel S. , Huggett Megan J. , Gaston Troy F. 
Published: October 2024

Globally, key predators such as lobsters are thought to control urchins. In south-eastern Australia, the role of Sagmariasus verreauxi (eastern rock lobster) as a key predator of the native urchin Centrostephanus rodgersii (long-spined urchin) has been questioned while the sympatric Heliocidaris erythrogramma (short-spined urchin) may be eaten more frequently. To test this, we tethered and filmed 100 urchins (50 C. rodgersii and 50 H. erythrogramma) outside of a lobster den over 25 nights to identify predators and quantify predation rates, time to feeding onset and handling time. Sagmariasus verreauxi exhibited very low predation rates (4%), despite being filmed walking past urchins repeatedly whereas Heterodontus galeatus (crested horn shark) was the main predator (45%). Predation rates by all predators (lobsters and sharks) were influenced primarily by tethering night but not urchin size or species. Predation increased throughout the study and while H. erythrogramma and C. rodgersii were eaten at similar rates, there was a trend for lobsters to eat H. erythrogramma and sharks to eat C. rodgersii. Feeding onset had no significant predictors though large C. rodgersii took longer to handle during feeding for both predators. Importantly, sharks readily consumed 25 C. rodgersii up to 121 mm Test Diameter (TD) while lobsters only ate one C. rodgersii (58 mm TD). These findings, although from only one test location, provide important insights into the species eating urchins and highlight the potential significance of overlooked predators such as H. galeatus.
Association of trimethylamine oxide and its precursors with cognitive impairment: a systematic review and meta-analysis
Authors: Long Caiyi , Li Zihan , Feng Haoyue , Jiang Yayi , Pu Yueheng , Tao Jiajing , Yue Rensong 
Published: October 2024

ObjectivesThe role of trimethylamine oxide (TMAO) in patients with cognitive impairment remains controversial. This study aimed to assess the association between TMAO and its precursors and the prevalence of cognitive impairment.MethodsPubMed, Embase, and Web of Science databases were searched for studies that met the inclusion criteria from their inception to 14 September 2024, and references were manually searched to identify any additions. Odds ratio (OR) was assessed by random-effects modeling, subgroup analyses to identify potential sources of heterogeneity, and the Newcastle-Ottawa Scale (NOS) and the Agency for Healthcare Research and Quality (AHRQ) Inventory for qualitative evaluation.ResultsNine studies involving 82,246 participants were included in the analysis. Meta-analyses suggested that elevated TMAO levels were strongly associated with an increased risk of cognitive impairment (OR: 1.39, 95% confidence interval [95%CI]: 1.09–1.77, p &lt; 0.05, I2:60%), and consistent results were obtained across all subgroups examined and sensitivity analyses. However, in the TMAO dose–response meta-analysis and TMAO precursor meta-analyses, the results were not significantly different (dietary choline: OR: 0.93, 95%CI: 0.78–1.10, p = 0.385, I2:68%, plasma choline: OR: 0.65, 95%CI: 0.41–1.02, p = 0.063, I2:76%, plasma betaine: OR: 0.74, 95%CI: 0.52–1.05, p = 0.094, I2:61%).ConclusionWe found that high TMAO concentrations were positively associated with the risk of cognitive impairment. TMAO is expected to be a potential risk predictor and therapeutic target for cognitive impairment. However, more high-quality studies are needed to further investigate the dose relationship between circulating TMAO concentrations and cognitive impairment.Systematic review registrationPROSPERO, identifier: CRD42023464543.
Meta-analysis: accuracy of the Baveno VI criteria for the diagnosis of high-risk varices in patients with hepatocellular carcinoma
Authors: Zheng Xiaoqin , Mei Tingting , Xu Hui , Yin Heran , Jin Hua , Gou Chunyan , Wang Xiaojun , Ding Huiguo 
Published: October 2024

Background and aimDiagnosing high-risk varices (HRV) is crucial for determining the prognosis and treatment strategy in patients with hepatocellular carcinoma (HCC). Although the Baveno VI consensus guidelines have been validated for assessing HRV in patients with liver cirrhosis, their applicability to those with HCC remains uncertain. This study aims to evaluate the effectiveness of the Baveno VI criteria in screening for HRV in patients with HCC.MethodsWe searched for English-language articles related to Baveno criteria and HCC across PubMed, Embase, Web of Science, and Cochrane databases, covering publications from their inception until April 19, 2024. Our meta-analysis was conducted using STATA 14.0 and Meta-Disc 1.4 software. We assessed the quality of the included studies using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. We analyzed pooled sensitivity (SEN), specificity (SPE), diagnostic odds ratio (DOR), positive likelihood ratio (LR+), and negative likelihood ratio (LR-) using a random-effects model and constructed a summary receiver operating characteristic (SROC) curve. Based on established consensus, the favorable Baveno VI criteria were defined as a liver stiffness measurement (LSM) &lt; 20 kPa and a platelet count (PLT) &gt; 150×109/L to exclude HRV. This study is registered with PROSPERO under the registration number CRD42024533946.ResultsWe finally brought four studies, including 1277 patients with HCC, into this meta-analysis. The SEN, SPE, DOR, and AUC of favorable Baveno VI criteria in screening HRV in patients with HCC were 0.90 (95% CI: 0.81–0.95), 0.33 (95% CI: 0.25–0.41), 4.44 (95% CI: 2.14–9.22), and 0.59 (95% CI: 0.55–0.64), respectively. The LR+ and LR- of the favorable Baveno VI criteria were 1.34 (95% CI: 1.19–1.50) and 0.30 (95% CI: 0.16–0.58), respectively. Subgroup and meta-regression analyses indicated that BCLC and Child-Pugh stages likely contribute to the heterogeneity in the SPE.ConclusionsThe favorable Baveno VI criteria may not effectively screen HRV in patients with HCC. However, the current evidence is insufficient, and further studies with larger sample sizes and detailed patient subgroups are needed.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42024533946.