Metabolomics and proteomics insights into subacute ruminal acidosis etiology and inhibition of proliferation of yak rumen epithelial cells in vitro.

BACKGROUND: Untargeted metabolomics and proteomics were employed to investigate the intracellular response of yak rumen epithelial cells (YRECs) to conditions mimicking subacute rumen acidosis (SARA) etiology, including exposure to short-chain fatty acids (SCFA), low pH5.5 (Acid), and lipopolysaccharide (LPS) exposure for 24 h. RESULTS: These treatments significantly altered the cellular morphology of YRECs. Metabolomic analysis identified significant perturbations with SCFA, Acid and LPS treatment affecting 259, 245 and 196 metabolites (VIP > 1, P < 0.05, and fold change (FC) ≥ 1.5 or FC ≤ 0.667). Proteomic analysis revealed that treatment with SCFA, Acid, and LPS resulted in differential expression of 1251, 1396, and 242 proteins, respectively (FC ≥ 1.2 or ≤ 0.83, P < 0.05, FDR < 1%). Treatment with SCFA induced elevated levels of metabolites involved in purine metabolism, glutathione metabolism, and arginine biosynthesis, and dysregulated proteins associated with actin cytoskeleton organization and ribosome pathways. Furthermore, SCFA reduced the number, morphology, and functionality of mitochondria, leading to oxidative damage and inhibition of cell survival. Gene expression analysis revealed a decrease the genes expression of the cytoskeleton and cell cycle, while the genes expression associated with inflammation and autophagy increased (P < 0.05). Acid exposure altered metabolites related to purine metabolism, and affected proteins associated with complement and coagulation cascades and RNA degradation. Acid also leads to mitochondrial dysfunction, alterations in mitochondrial integrity, and reduced ATP generation. It also causes actin filaments to change from filamentous to punctate, affecting cellular cytoskeletal function, and increases inflammation-related molecules, indicating the promotion of inflammatory responses and cellular damage (P < 0.05). LPS treatment induced differential expression of proteins involved in the TNF signaling pathway and cytokine-cytokine receptor interaction, accompanied by alterations in metabolites associated with arachidonic acid metabolism and MAPK signaling (P < 0.05). The inflammatory response and activation of signaling pathways induced by LPS treatment were also confirmed through protein interaction network analysis. The integrated analysis reveals co-enrichment of proteins and metabolites in cellular signaling and metabolic pathways. CONCLUSIONS: In summary, this study contributes to a comprehensive understanding of the detrimental effects of SARA-associated factors on YRECs, elucidating their molecular mechanisms and providing potential therapeutic targets for mitigating SARA.

Proteomics Reveals the Obstruction of Cellular ATP Synthesis in the Ruminal Epithelium of Growth-Retarded Yaks.

Growth-retarded yaks are of a high proportion on the Tibetan plateau and reduce the economic income of farmers. Our previous studies discovered a maldevelopment in the ruminal epithelium of growth-retarded yaks, but the molecular mechanisms are still unclear. This study aimed to reveal how the proteomic profile in the ruminal epithelium contributed to the growth retardation of yaks. The proteome of the ruminal epithelium was detected using a high-resolution mass spectrometer. There were 52 proteins significantly differently expressed between the ruminal epithelium of growth-retarded yaks and growth-normal yaks, with 32 downregulated and 20 upregulated in growth-retarded yaks. Functional analysis showed the differently expressed proteins involved in the synthesis and degradation of ketone bodies (p = 0.012), propanoate metabolism (p = 0.018), pyruvate metabolism (p = 0.020), and mineral absorption (p = 0.024). The protein expressions of SLC26A3 and FTH1, enriched in the mineral absorption, were significantly downregulated in growth-retarded yaks. The key enzymes ACAT2 and HMGCS2 enriched in ketone bodies synthesis and key enzyme PCCA enriched in propanoate metabolism had lower protein expressions in the ruminal epithelium of growth-retarded yaks. The ATP concentration and relative mitochondrial DNA copy number in the ruminal epithelium of growth-normal yaks were dramatically higher than those of growth-retarded yaks (p < 0.05). The activities of citrate synthase (CS), the α-ketoglutarate dehydrogenase complex (α-KGDHC), isocitrate dehydrogenase (ICD) in the tricarboxylic acid cycle (TCA), and the mitochondrial respiratory chain complex (MRCC) were significantly decreased in ruminal epithelium of growth-retarded yaks compared to growth-normal yaks (p < 0.05). The mRNA expressions of COQ9, COX4, and LDHA, which are the encoding genes in MRCC I, IV and anaerobic respiration, were also significantly decreased in the ruminal epithelium of growth-retarded yaks (p < 0.05). Correlation analysis revealed that the average daily gain (ADG) was significantly positively correlated to the relative mitochondrial DNA copy number (p < 0.01, r = 0.772) and ATP concentration (p < 0.01, r = 0.728) in the ruminal epithelium, respectively. The ruminal weight was positively correlated to the relative mitochondrial DNA copy number (p < 0.05, r = 0.631) and ATP concentration in ruminal epithelium (p < 0.01, r = 0.957), respectively. The ruminal papillae had a significant positive correlation with ATP concentration in ruminal epithelium (p < 0.01, r = 0.770). These results suggested that growth-retarded yaks had a lower VFA metabolism, ketone bodies synthesis, ion absorption, and ATP synthesis in the ruminal epithelium; it also indicated that the growth retardation of yaks is related to the obstruction of cellular ATP synthesis in rumen epithelial cells.

Carbohydrate quality, not quantity, linked to reduced colorectal cancer incidence and mortality in US populations: evidence from a prospective study.

BACKGROUND: Carbohydrates have been implicated in colorectal cancer (CRC) risk, but the specific impact of carbohydrate quality and quantity on CRC susceptibility in US populations remains unclear. METHODS: We followed 101,694 participants from Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. The carbohydrate quality index (CQI) and low-carbohydrate diet score (LCDs) were used to evaluate the daily carbohydrate quality and quantity separately, where higher scores indicated greater adherence. Cox proportional hazards regression was used to compute HRs and 95% CIs for incident CRC and related death. Subgroup analyses were conducted to identify potential effect modifiers. RESULTS: During follow-up, we documented 1085 incident cases of CRC, of whom 311 died from CRC. Individuals in the highest compared with the lowest quartiles of CQI had a lower CRC incidence (Q4 vs Q1: HR 0.80, 95% CI 0.67-0.96, Ptrend = 0.012) and mortality (Q4 vs Q1: HR 0.61, 95% CI 0.44-0.86, Ptrend = 0.004). The inverse association between CQI and CRC risk was observed for distal colon and rectum but not for proximal colon cancer. Regarding mortality, this association was only significant for rectum cancer. Subgroup analyses indicated this inverse association of CQI with CRC risk was only observed in participants with lower LCDs. No significant associations were found between LCDs and CRC incidence or mortality. CONCLUSIONS: Our findings suggest focusing on higher quality, rather than restricting the quantity, of carbohydrate consumption may be an effective approach to reduce the risk of CRC in the US population, particularly for distal colon and rectal cancers.

SALL4 advances the proliferation and tumor cell stemness of colon cancer cells through the transcription and regulation of ROBO2.

SALL4 is a transcription factor highly expressed in diverse cancers and is implicated in the development of cancer. SALL4 has been implied to play a cancer-promoting role in colon cancer (CC), but the molecular mechanism remains unclear. Chromatin immunoprecipitation assay and dual-luciferase assay were conducted to verify the binding relationship of SALL4 and ROBO2. qRT-PCR detected the mRNA expression levels of SALL4 and ROBO2, and the flow cytometry analyzed the cell cycle distribution. Western blot examined SALL4 expression, and cell cycle/cell stemness-related proteins. The impact of SALL4 and ROBO2 on the proliferation capacity of cells and tumor cell stemness was elucidated by MTT, colony formation, and sphere-forming assays. SALL4 and ROBO2 were up-regulated in CC, and SALL4 could activate the transcription of ROBO2. Down-regulated SALL4 was able to significantly restrain the proliferation capacity of CC cells and arrest the cell cycle in G0/G1 phase by repressing the expression of cyclin B, cyclin E, and cyclin D1. Besides, the rescue assay results indicated that up-regulated ROBO2 could reverse the repressive impact of down-regulated SALL4 on the proliferation of CC cells and accelerate the progression of the cell cycle, thus promoting the sphere-forming of tumor stem cells. SALL4 advanced the proliferation of CC and cell stemness through direct activation of ROBO2 expression, implied the novel mechanism of SALL4 in CC, and pointed out that SALL4/ROBO2 axis was likely to be a potential target for clinical treatment of CC.

Compliance with the EAT-Lancet diet and risk of colorectal cancer: a prospective cohort study in 98,415 American adults.

Background: The EAT-Lancet diet (ELD) is a recommended dietary pattern for achieving simultaneous improvements in both individual health and environmental sustainability. While research on the association between ELD and colorectal cancer (CRC) remains scarce, the potential impact of nutrition on CRC prevention and progression is a topic of growing interest. This study aims to investigate the relationship between adherence to the ELD and the risk of CRC, shedding light on the role of nutrition in CRC prevention. Methods: A total of 98,415 participants were included. A Diet History Questionnaire (DHQ) was used to collect dietary information, and an ELD score was used to assess adherence to ELD. Higher scores indicated greater adherence. Cox hazard regression analyses were conducted to examine whether there were associations between the ELD score and CRC risk. The restricted cubic spline (RCS) model was used to further explore the dose-response association between the ELD score and CRC incidence. Subgroup analyses were conducted to identify potential modifiers that interacted with ELD on CRC incidence, and sensitivity analyses were performed to evaluate the robustness of the established association. Results: During a mean follow-up of 8.82 years, a total of 1,054 CRC cases were documented. We found a statistically significant correlation between the ELD score and CRC risk (Q4 vs. Q1: HR 0.81, 95% CI 0.67-0.98; P for trend = 0.034) after adjusting for potential confounders. No statistically significant associations were discovered between ELD adherence and CRC by anatomical site. Subgroup analyses found no interactional factor, sensitivity analyses, and the RCS model showed a robustness and linearity association (P-linearity >0.05). Conclusion: We concluded that adherence to ELD contributes to the prevention of CRC.

Association of diabetes risk reduction diet with renal cancer risk in 101,755 participants: a prospective study.

BACKGROUND: There is little prospective evidence exists about whether adherence to a diabetes risk reduction diet (DRRD) is related to a significant reduction in renal cancer risk. We sought to clarify whether adherence to DRRD was associated with a reduced risk of renal cancer in a US population. METHODS: A population-based cohort of 101,755 American adults was identified from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. A DRRD score was calculated to assess adherence to this dietary pattern, where increased scores indicated greater adherence. The relationship between DRRD score and risk of renal cancer was assessed based on the hazard ratios (HRs) and 95% confidence intervals (CIs), which were both calculated using Cox regression. Non-linear association was determined through restricted cubic spline regression. Potential effect modifiers were identified through subgroup analyses. RESULTS: Over a mean follow-up of 8.8 years, 446 renal cancers were detected. In this analysis, the fully adjusted model depicted a notable 29% reduction in the risk of renal cancer among individuals in the highest quartile of DRRD score in comparison with the lowest quartile individuals (HRQ4 vs. Q1: 0.71; 95% CI = 0.54, 0.94; Ptrend = 0.008). This association remained consistent across a series of sensitivity analyses. A non-linear inverse dose-response association between renal cancer risk with DRRD score was observed (Pnonlinearity = 0.026). Subgroup analyses showed that this favorable link was more prominent in participants with low Healthy Eating Index-2015 (Pinteraction = 0.015). Regarding the individual components of DRRD, a decrease in the risk of renal cancer was linked to increased intake of cereal fiber and whole fruit, and lower sugar-sweetened beverage consumption (all Ptrend < 0.05). CONCLUSIONS: Our findings indicate that individuals adhering to DRRD are associated with a reduction in the risk of renal cancer.

Establishment of SV40 Large T-Antigen-Immortalized Yak Rumen Fibroblast Cell Line and the Fibroblast Responses to Lipopolysaccharide.

The yak lives in harsh alpine environments and the rumen plays a crucial role in the digestive system. Rumen-associated cells have unique adaptations and functions. The yak rumen fibroblast cell line (SV40T-YFB) was immortalized by introducing simian virus 40 large T antigen (SV40T) by lentivirus-mediated transfection. Further, we have reported the effects of lipopolysaccharide (LPS) of different concentrations on cell proliferation, extracellular matrix (ECM), and proinflammatory mediators in SV40T-YFB. The results showed that the immortalized yak rumen fibroblast cell lines were identified as fibroblasts that presented oval nuclei, a fusiform shape, and positive vimentin and SV40T staining after stable passage. Chromosome karyotype analysis showed diploid characteristics of yak (n = 60). LPS at different concentrations inhibited cell viability in a dose-dependent manner. SV40T-YFB treated with LPS increased mRNA expression levels of matrix metalloproteinases (MMP-2 and MMP-9), inflammatory cytokines (TNF-α, IL-1ß, IL-6), and urokinase-type plasminogen activator system components (uPA, uPAR). LPS inhibits the expression of tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2), plasminogen activator inhibitor-2 (PAI-2), fibronectin (FN), anti-inflammatory factor IL-10, and collagen I (COL I) in SV40T-YFB. Overall, these results suggest that LPS inhibits cell proliferation and induces ECM degradation and inflammatory response in SV40T-YFB.

Immunogenicity and safety of an Escherichia coli-produced human papillomavirus (types 6/11/16/18/31/33/45/52/58) L1 virus-like-particle vaccine: a phase 2 double-blind, randomized, controlled trial.

The Escherichia coli-produced human papillomavirus (HPV) 16/18 bivalent vaccine (Cecolin) has received prequalification by the World Health Organization based on its high efficacy and good safety profile. We aimed to evaluate the immunogenicity and safety of the second-generation nonavalent HPV 6/11/16/18/31/33/45/52/58 vaccine (Cecolin 9) through the randomized, blinded phase 2 clinical trial. Eligible healthy women aged 18-45 years were randomly (1:1) allocated to receive three doses of 1.0 mL (270 µg) of Cecolin 9 or placebo with a 0-1-6-month schedule. The primary endpoint was the seroconversion rate and geometric mean titer of neutralizing antibodies (nAbs) one month after the full vaccination course (month 7). The secondary endpoint was the safety profile including solicited adverse reactions occurring within 7 d, adverse events (AEs) occurring within 30 d after each dose, and serious adverse events (SAEs) occurring during the 7-month follow-up period. In total, 627 volunteers were enrolled and randomly assigned to Cecolin 9 (n = 313) or placebo (n = 314) group in Jiangsu Province, China. Almost all participants in the per-protocol set for immunogenicity (PPS-I) seroconverted for nAbs against all the nine HPV types at month 7, while two failed to seroconvert for HPV 11 and one did not seroconvert for HPV 52. The incidence rates of total AEs in the Cecolin 9 and placebo groups were 80.8% and 72.9%, respectively, with the majority of them being mild and recovering shortly. None of the SAEs were considered related to vaccination. In conclusion, the E. coli-produced 9-valent HPV (9vHPV) vaccine candidate was well tolerated and immunogenic, which warrants further efficacy studies in larger populations.

Association between sulfur microbial diet and the risk of colorectal cancer precursors in older adults.

Background: Sulfur microbial diet (SMD), related to the enrichment of sulfur-metabolizing gut bacteria, has been confirmed to be linked to an elevated risk of early-onset colorectal adenoma in young females. However, it remains unclear whether SMD is associated with the risk of colorectal adenoma in older people, who are at greater risk for colorectal cancer. Methods: All data on participants in this study were retrieved from the intervention arm of the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening test. Participants' adherence to this dietary pattern was assessed using SMD score. Hazard ratios (HR) and 95% confidence intervals (CI) were adopted in Cox proportional hazards regression models to assess the link between SMD score and the incidence of colorectal adenoma in participants included in the study. Specific stratified analyses were constructed to assess whether this association changed in different conditions, whereas the robustness of the association was examined through sensitivity analyses. Results: The mean baseline age of participants was 62.1 (SD 5.2) years (range 54.0-75.0 years). During 19,468,589 person-years of follow-up, 992 colorectal adenoma cases were documented in a total of 17,627 included participants. In a fully adjusted model, an increased risk of colorectal adenoma was determined in participants in the highest quartile of SMD score in comparison with those in the lowest quartile (HRquartile4 vs. HRquartile1 = 1.23; 95% CI: 1.02, 1.47; p = 0.017 for trend). This positive association between SMD score and adenoma risk was more evident in participants who were current or former smokers (p = 0.029 for interaction). Conclusion: In this study, our results support a role for the SMD in the carcinogenicity of colorectal cancer precursors among older adults. Nevertheless, these results require validation through more research.

Intact glycopeptides identified by LC-MS/MS as biomarkers for response to chemotherapy of locally advanced cervical cancer.

Objective: For locally advanced cervical cancer (LACC), patients who respond to chemotherapy have a potential survival advantage compared to nonresponsive patients. Thus, it is necessary to explore specific biological markers for the efficacy of chemotherapy, which is beneficial to personalized treatment. Methods: In the present study, we performed a comprehensive screening of site-specific N-glycopeptides in serum glycoproteins to identify glycopeptide markers for predicting the efficacy of chemotherapy, which is beneficial to personalized treatment. In total, 20 serum samples before and after neoadjuvant chemotherapy (NACT) from 10 LACC patients (NACT response, n=6) and NACT nonresponse, n=4) cases) were analyzed using LC-MS/MS, and 20 sets of mass spectrometry (MS) data were collected using liquid chromatography coupled with high-energy collisional dissociation tandem MS (LC-HCD-MS/MS) for quantitative analysis on the novel software platform, Byos. We also identified differential glycopeptides before and after chemotherapy in chemo-sensitive and chemo-resistant patients. Results: In the present study, a total of 148 glycoproteins, 496 glycosylation sites and 2279 complete glycopeptides were identified in serum samples of LACC patients. Before and after chemotherapy, there were 13 differentially expressed glycoproteins, 654 differentially expressed glycopeptides and 93 differentially expressed glycosites in the NACT responsive group, whereas there were 18 differentially expressed glycoproteins, 569 differentially expressed glycopeptides and 99 differentially expressed glycosites in the NACT nonresponsive group. After quantitative analysis, 6 of 570 glycopeptides were identified as biomarkers for predicting the sensitivity of neoadjuvant chemotherapy in LACC. The corresponding glycopeptides included MASP1, LUM, ATRN, CO8A, CO8B and CO6. The relative abundances of the six glycopeptides, including MASP1, LUM, ATRN, CO8A, CO8B and CO6, were significantly higher in the NACT-responsive group and were significantly decreased after chemotherapy. High levels of these six glycopeptides may indicate that chemotherapy is effective. Thus, these glycopeptides are expected to serve as biomarkers for predicting the efficacy of neoadjuvant chemotherapy in locally advanced cervical cancer. Conclusion: The present study revealed that the N-glycopeptide of MASP1, LUM, ATRN, CO8A, CO8B and CO6 may be potential biomarkers for predicting the efficacy of chemotherapy for cervical cancer.

Predictive factors on postoperative venous thromboembolism after minimally invasive colorectal cancer surgery: a retrospective observational study.

BACKGROUND: Venous thromboembolism (VTE) is a serious and preventable postoperative complication. However, the predictive significance of perioperative biochemical parameters for VTE after minimally invasive colorectal cancer surgery remains unclear. METHODS: A total of 149 patients undergoing minimally invasive colorectal cancer surgery were collected between October 2021 and October 2022. Biochemical parameters related to preoperative and postoperative day 1, day 3, and day 5 were collected, including D-Dimer, mean platelet volume (MPV), and maximum amplitude (MA) of thromboelastography (TEG). Receiver operating characteristic (ROC) curves were used to explore the predictive powers of meaningful biochemical parameters for postoperative VTE, and calibration curves were used to assess predictive accuracy. RESULTS: The overall cumulative incidence of VTE was 8.1% (12/149). The preoperative and postoperative day 3 D-Dimer, postoperative day 3, and day 5 MPV, and postoperative day 1, day 3, and day 5 TEG-MA was significantly higher in the VTE group than in the non-VTE group (P < 0.05). The results of both the ROC curve and the calibration curve indicated that these meaningful D-Dimer, MPV, and TEG-MA had moderate discrimination and consistency for postoperative VTE. CONCLUSIONS: D-Dimer, MPV, and TEG-MA may predict postoperative VTE in patients undergoing minimally invasive surgery for colorectal cancer at specific times in the perioperative period.

Fus3/Kss1-MAP kinase and Ste12-like control distinct biocontrol-traits besides regulation of insect cuticle penetration via phosphorylation cascade in a filamentous fungal pathogen.

BACKGROUND: Homolog of the yeast Fus3/Kss1 mitogen-activated protein kinase (MAPK) pathway and its target transcription factor, Ste12-like, are involved in penetration of host cuticle/pathogenicity in many ascomycete pathogens. However, details of their interaction during fungal infection, as well as their controlled other virulence-associated traits, are unclear. RESULTS: Ste12-like (BbSte12) and Fus3/Kss1 MAPK homolog (Bbmpk1) interacted in nucleus, and phosphorylation of BbSte12 by Bbmpk1 was essential for penetration of insect cuticle in an insect fungal pathogen, Beauveria bassiana. However, some distinct biocontrol-traits were found to be mediated by Ste12 and Bbmpk1. In contrast to ΔBbmpk1 colony that grew more rapid than wild-type strain, inactivation of BbSte12 resulted in the opposite phenotype, which was consistent with their different proliferation rates in insect hemocoel after direct injection of conidia bypass the cuticle. Reduced conidial yield with decreased hydrophobicity was examined in both mutants, however they displayed distinct conidiogenesis, accompanying with differently altered cell cycle, distinct hyphal branching and septum formation. Moreover, ΔBbmpk1 showed increased tolerance to oxidative agent, whereas the opposite phenotype was seen for ΔBbSte12 strain. RNA sequencing analysis revealed that Bbmpk1 controlled 356 genes depending on BbSte12 during cuticle penetration, but 1077 and 584 genes were independently controlled by Bbmpk1 and BbSte12. CONCLUSION: BbSte12 and Bbmpk1 separately participate in additional pathways for control of conidiation, growth and hyphal differentiation, as well as oxidative stress response besides regulating cuticle penetration via phosphorylation cascade. © 2023 Society of Chemical Industry.

Suggestive evidence of CYP4F2 gene polymorphisms with HAPE susceptibility in the Chinese Han population.

High altitude pulmonary edema (HAPE) is a common respiratory disease in the high altitude area, which is rapid and harmful. We firstly conducted a case-control study to assess the potential association of CYP4F2 gene polymorphisms with HAPE susceptibility in the Chinese Han population. The study recruited 238 patients with HAPE and 230 healthy controls in Northwest China. Genomic DNA was extracted from blood samples, and gene polymorphisms were detected using the Agena MassARRAY platform. Odds ratios (ORs), 95% confidence intervals (95% CIs), and P-value were used to evaluate the relationship between HAPE risk and CYP4F2 gene polymorphisms. Multi-factor dimension reduction (MDR) was used to assess the optimal interaction of CYP4F2 gene polymorphisms on HAPE risk. We found rs3093193 was shown to reduce the risk of HAPE (OR = 0.70, 95% CI = 0.52-0.93, P = 0.014), while rs12459936 was increased the susceptibility to HAPE (OR = 2.08, 95% CI = 1.33-3.26, P = 0.001). Age stratified analysis revealed that rs3093193 and rs12459936 were correlated with HAPE risk in people at age > 32 years old, and rs3093193 and rs3093110 were correlated with the HAPE risk in people at age ≤ 32 years old. Gender stratification analysis was found that rs3093193, rs12459936, and rs3093110 were all related to HAPE risk in males. A combination of rs12459936 and rs3093110 was the best multi-loci model with the highest testing accuracy. Our study is the first to provide the association between CYP4F2 gene polymorphisms and HAPE risk in the Chinese Han population.

Prognosis of hepatitis E infection in patients with chronic liver disease: A meta-analysis.

In individuals with underlying chronic liver disease (CLD), hepatitis E virus (HEV) infection is a potential trigger of acute-on-chronic liver failure. In this systematic review, seven electronic databases were searched. Pooled incidence rates with 95% confidence intervals (95% CIs) were calculated by the Freeman-Tukey double arcsine transformation method. The association between death or liver failure and HEV superinfection in CLD patients was estimated by the odds ratios (OR) with a 95% CI. A total of 18 studies from 5 countries were eligible for systematic review. The prevalence of acute HEV infection in hospitalized CLD patients with clinical manifestations of hepatitis was 13.6%, which was significantly higher than that in CLD patients from the community (pooled prevalence 1.1%). The overall rates of liver failure and mortality in CLD patients with HEV superinfection were 35.8% (95% CI: 26.7%-45.6%) and 14.3% (95% CI: 10.6%-18.5%), respectively, with the rates in cirrhotic patients being approximately 2-fold and 4-fold higher than those in noncirrhotic patients, respectively. The risks of liver failure (OR = 5.5, 95% CI: 1.5-20.1) and mortality (OR = 5.0, 95% CI: 1.9-13.3) were significantly higher in CLD patients with HEV superinfection than in those without HEV superinfection. HEV testing in hospitalized CLD patients is necessary due to the high prevalence of HEV infection observed in hospitalized CLD patients. HEV superinfection could accelerate disease progression in patients with underlying CLD and increase mortality in these patients. HEV vaccination is appropriate for patients with pre-existing CLD.

Association between oxidative stress exposure and colorectal cancer risk in 98,395 participants: results from a prospective study.

Background: The intricate role of oxidative stress (OS) in colorectal cancer (CRC) initiation is underscored by an imbalance between pro-oxidants and antioxidants. Utilizing the Oxidative Balance Score (OBS) as a metric, this study aims to investigate the association between OS exposure and CRC risk, while also examining potential sex-specific differences in a large U.S. cohort. Methods: The study included 98,395 adults from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. To construct the OBS, 14 dietary and lifestyle factors intricately associated with oxidative stress were quantified. A higher OBS value indicated a more favorable oxidative balance pattern or diminished OS exposure. Due to sex-specific differences in OBS, associations were evaluated separately for men and women based on Cox regression analysis. Subgroup analyses were conducted to elucidate potential modifiers. Results: During 867,963.4 person-years of follow-up, 1,054 CRCs occurred. The mean (SD) age and OBS were 65.52 (5.73) years and 14.09 (3.95) points, respectively. In the fully adjusted Cox model, we observed an inverse association between OBS and CRC incidence in women (HRQ5vsQ1: 0.72; 95% CI: 0.52, 0.99; P for trend = 0.018) but not men. Subgroup analyses revealed the inverse association was more pronounced among women without versus with a family history of CRC (HRQ5 vsQ1: 0.66, 95% CI: 0.47-0.93; P for trend = 0.001; P for interaction = 0.001). The results remained robust after several sensitivity analyses. Conclusion: Higher OBS was associated with lower CRC risk in women but not men; this inverse association was stronger among women without a family history of CRC. These findings suggest exposure to OS may confer sex-specific CRC risk effects, especially for women without a family history of CRC.

Association between low-fat diet and liver cancer risk in 98,455 participants: Results from a prospective study.

Background: Low-fat diet reduces the risk of chronic metabolic diseases such as obesity and diabetes, which exhibit overlapping mechanisms with liver cancer. However, the association between low-fat diet and liver cancer risk remains unclear. Aim: To investigate whether adherence to low-fat diet is associated with a reduced risk of liver cancer in a prospective study. Materials and methods: Data of participants in this study were collected from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. A low-fat diet score was calculated to reflect adherence to low-fat dietary pattern, with higher scores indicating greater adherence. Cox regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for liver cancer incidence with adjustment for potential covariates. Restricted cubic spline model was used to characterize liver cancer risk across the full range of the low-fat diet score. Prespecified subgroup analyses were used to identify potential impact modifiers. Sensitivity analyses were performed to test the robustness of this association. Results: A total of 98,455 participants were included in the present analysis. The mean (standard deviation) age, low-fat diet score, and follow-up time were 65.52 (5.73) years, 14.99 (6.27) points, and 8.86 (1.90) years, respectively. During 872639.5 person-years of follow-up, 91 liver cancers occurred, with an overall incidence rate of 0.01 cases per 100 person-years. In the fully adjusted Cox model, the highest versus the lowest quartile of low-fat diet score was found to be associated with a reduced risk of liver cancer (HR Q4 vs. Q1: 0.458; 95% CI: 0.218, 0.964; P = 0.035 for trend), which remained associated through a series of sensitivity analyses. The restricted cubic spline model showed a linear dose-response association between low-fat diet score and liver cancer incidence (p = 0.482 for non-linear). Subgroup analyses did not show significant interaction between low-fat diet score and potential impact modifiers in the incidence of liver cancer. Conclusion: In this study, low-fat diet score is associated with reduced liver cancer risk in the US population, indicating that adherence to low-fat diet may be helpful for liver cancer prevention. Future studies should validate our findings in other populations.

Integration of transcriptomic and metabolomic analysis of the mechanism of dietary N-carbamoylglutamate in promoting follicle development in yaks.

Yak is the main livestock in the highlands of China. The low reproductive rate of yaks is a serious constraint on their production and utility. N-carbamylglutamate (NCG) can increase arginine synthesis in mammals and has been shown to improve reproductive performance. Twelve multiparous and simutaneous anoestrous female yaks were randomly divided into two groups, one of which was fed the basal diet (Control, n = 6), and the other was fed the basal diet supplemented with NCG at 6 g/day/yak (NCG, n = 6). All yaks were slaughtered on the 32nd day (the time predicted for the selection of the last wave of dominant follicles), and their ovarian tissues were collected and follicles were classified. NCG supplementation increased the number of large ovarian follicles (diameter > 10 mm), as well as caused significant changes in the transcriptional and metabolic levels in yak ovaries which due to the differential expression of 889 genes and 94 metabolites. Integrated analysis of the transcriptomics and metabolomics data revealed that the differentially expressed genes and differential metabolites were primarily involved in the process of energy metabolism, amino acid metabolic pathways, carbohydrate metabolic pathways, and lipid metabolic pathways. The highlighted changes were associated with amino acid synthesis and metabolism, ovarian steroid hormone synthesis, the pentose phosphate pathway, and the tricarboxylic acid cycle, suggesting that NCG supplementation may promote estrogen synthesis and help regulate follicular development by altering the pathways associated with glucose catabolism. The results present important clues for understanding the mechanisms by which NCG supplementation promotes follicular development in yaks. The findings of this study provide a basis for the development and application of NCG in optimizing animal reproduction, including yak reproductive performance, which may help optimize livestock management and uplift the pastoral economy.

Establishment of Immortalized Yak Ruminal Epithelial Cell Lines by Lentivirus-Mediated SV40T and hTERT Gene Transduction.

Yak is a unique species of cattle that is adapted to the harsh natural environment of the Qinghai-Tibet Plateau. Research on the function of the yak rumen is limited to animal experiments, and the cell molecular mechanism is very limited. The high cost of isolation and culture of adult yak rumen epithelial cells (YRECs), low success rate, and limited cell life limit the scope of long-term physiological functions and nutrient absorption mechanisms of yak rumen epithelium in vitro studies. This study aimed to explore the isolation and immortal culture methods of primary YRECs and establish a new cell line model for studying cell molecular mechanisms. The human telomerase reverse transcriptase gene (hTERT) and simian virus 40 large T antigen (SV40T) were transferred into primary YDECs using mammalian gene expression lentiviral vectors. The immortalized cell line (SV40T-YREC-hTERT) retains the morphological and functional characteristics of primary cells. The epithelial cell marker protein cytokeratin 18 of the immortalized cell lines was positive, and the cell proliferation and karyotype were normal. The SV40T and hTERT genes were successfully transferred into immortalized cell lines and maintained high expression. Simultaneously, the immortalized cell lines had normal function of short-chain fatty acid (SCFA) transport and absorption, and the immortalized yak rumen epithelial cell lines were successfully established. In addition, the transepithelial electrical resistance value gradually increased with culture time, and the permeability of epithelial cells decreased by culturing epithelial cells in Transwell culture chambers. Transmission electron microscopy demonstrated the submicroscopic structure of cells in the integrity barrier model and established the YREC barrier model in vitro.

MIR17HG polymorphisms contribute to high-altitude pulmonary edema susceptibility in the Chinese population.

High-altitude pulmonary edema (HAPE) is a common acute altitude sickness. This study was designed to investigate the effect of MIR17HG polymorphisms on HAPE risk in the Chinese population. The Agena MassARRAY platform was used to genotype six single-nucleotide polymorphisms (SNPs) in the MIR17HG gene in 244 HAPE patients and 243 non-HAPE controls. The odds ratio (OR) and 95% confidence interval were used to evaluate the association between each MIR17HG polymorphisms and the risk of HAPE under a polygenetic model. Statistical analysis was performed using the χ2 test. Multifactor dimensionality reduction (MDR) analysis was used to analyze the impacts of SNP-SNP interactions on the risk of HAPE. According to the allele model, the HAPE risk of people with the rs7318578 A allele of MIR17HG was lower than that of people with the C allele (OR 0.74, p = 0.036).Logistic regression analysis of four models for all selected MIR17HG SNPs showed significant differences in the frequencies of rs7318578 (OR 0.74, p = 0.037) and rs17735387 (OR 1.51, p = 0.036) between cases and controls. The results of the sex stratification analysis showed that among males, rs17735387 in the MIR17HG gene is associated with an increased risk of HAPE. MDR analysis showed that the best combination model was a three-locus model incorporating rs72640334, rs7318578, and rs7336610. This study revealed the correlations between rs7318578 and rs17735387 on the MIR17HG gene and the risk of HAPE in the Chinese population, providing a theoretical basis for the early screening, prevention, and diagnosis of HAPE in high-risk populations.

Comparison of coated and uncoated trace elements on growth performance, apparent digestibility, intestinal development and microbial diversity in growing sheep.

The suitable supplement pattern affects the digestion and absorption of trace minerals by ruminants. This study aimed to compare the effects of coated and uncoated trace elements on growth performance, apparent digestibility, intestinal development and microbial diversity in growing sheep. Thirty 4-month-old male Yunnan semi-fine wool sheep were randomly assigned to three treatments (n = 10) and fed with following diets: basal diet without adding exogenous trace elements (CON), basal diet plus 400 mg/kg coated trace elements (CTE, the rumen passage rate was 65.87%) and basal diet plus an equal amount of trace elements in uncoated form (UTE). Compared with the CON group, the average daily weight gain and apparent digestibility of crude protein were higher (P < 0.05) in the CTE and UTE groups, while there was no difference between the CTE and UTE groups. The serum levels of selenium, iodine and cobalt were higher (P < 0.05) in the CTE and UTE groups than those in the CON group, the serum levels of selenium and cobalt were higher (P < 0.05) in the CTE group than those in the UTE group. Compared with the CON and UTE groups, the villus height and the ratio of villus height to crypt depth in duodenum and ileum were higher (P < 0.05) in the CTE groups. The addition of trace minerals in diet upregulated most of the relative gene expression of Ocludin, Claudin-1, Claudin-2, ZO-1, and ZO-2 in the duodenum and jejunum and metal ion transporters (FPN1 and ZNT4) in small intestine. The relative abundance of the genera Christensenellaceae R-7 group, Ruminococcus 1, Lachnospiraceae NK3A20 group, and Ruminococcaceae in ileum, and Ruminococcaceae UCG-014 and Lactobacillus in colon was higher in the CTE group that in the CON group. These results indicated that dietary trace mineral addition improved the growth performance and intestinal development, and altered the structure of intestinal bacteria in growing sheep. Compared to uncoated form, offering trace mineral elements to sheep in coated form had a higher absorption efficiency, however, had little effect on improving growth performance of growing sheep.