Causal association of sarcopenia with hepatocellular carcinoma risk in European population: a Mendelian randomization study

BackgroundThe causal association of sarcopenia with the incidence risk of hepatocellular carcinoma (HCC) in the European population, and the potential mediating role of C-reactive protein (CRP), remains unclear. This study employed a bidirectional two-sample, two-step Mendelian randomization (MR) analysis to investigate the causality and identify the mediator.MethodsSummary statistics for HCC, CRP, and sarcopenia-related traits, including appendicular lean mass (ALM), hand grip strength (HGS), and walking pace (WP), were acquired from publicly available databases. We conducted bidirectional MR and Steiger tests of directionality to check the presence of reverse causality. Additionally, a two-step MR analysis was used to assess the mediating effect of CRP in the causality between sarcopenia and HCC. Tests for heterogeneity and horizontal pleiotropy were performed.ResultsAs ALM increases, the risk of HCC occurrence decreases [odds ratio (OR), 95% confidence interval (CI): 0.703, 0.524–0.943; P = 0.019]. And, genetically predicted low-HGS (OR, 95%CI: 2.287, 1.013–5.164; P = 0.047) was associated with an increased incidence risk of HCC, with no reverse causality. However, we found no evidence supporting a causality between WP and HCC. CRP was identified as the mediator of the causal effect of ALM and low-HGS on HCC, with corresponding mediating effects of 9.1% and 7.4%.ConclusionsThis MR study effectively demonstrates that lower ALM and low-HGS are linked to an elevated risk of HCC within the European population, and the causality was not bidirectional. Furthermore, CRP serves as a mediator in the associations. These findings may help mitigate HCC risk among individuals with sarcopenia

Mutation characteristics of cancer susceptibility genes in Chinese ovarian cancer patients

IntroductionThe association between mutations in susceptibility genes and the occurrence of ovarian cancer has been extensively studied. Previous research has primarily concentrated on genes involved in the homologous recombination repair pathway, particularly BRCA1 and BRCA2. However, a wider range of genes related to the DNA damage response pathways has not been fully explored.MethodsTo investigate the mutation characteristics of cancer susceptibility genes in the Chinese ovarian cancer population and the associations between gene mutations and clinical data, this study initially gathered a total of 1171 Chinese ovarian cancer samples and compiled a dataset of germline mutations in 171 genes.ResultsIn this study, it was determined that MC1R and PRKDC were high-frequency ovarian cancer susceptibility genes in the Chinese population, exhibiting notable distinctions from those in European and American populations; moreover high-frequency mutation genes, such as MC1R: c.359T>C and PRKDC: c.10681T>A, typically had high-frequency mutation sites. Furthermore, we identified c.8187G>T as a characteristic mutation of BRCA2 in the Chinese population, and the CHEK2 mutation was significantly associated with the early onset of ovarian cancer, while the CDH1 and FAM175A mutations were more prevalent in Northeast China. Additionally, Fanconi anemia pathway-related genes were significantly associated with ovarian carcinogenesis.ConclusionIn summary, this research provided fundamental data support for the optimization of ovarian cancer gene screening policies and the determination of treatment, and contributed to the precise intervention and management of patients

PARP inhibitor maintenance treatment for newly diagnosed ovarian cancer patients: a real-world study from China

PurposeThis study evaluated the efficacy and safety in a real-world population of epithelial ovarian cancer (EOC) treated with poly (ADP-ribose) polymerase inhibitor (PARPi) as first-line maintenance therapy in the largest gynecologic oncology center in Western China.MethodsThis study included patients newly diagnosed EOC who received PARPi as first-line maintenance therapy in West China Second University Hospital from August 1, 2018 to September 31, 2022. The primary endpoints were progression-free survival (PFS) and safety evaluated by Common Terminology Criteria for Adverse Events Version 5.0(CTCAE 5.0). The secondary endpoints were overall survival (OS) and prognostic factors influencing the PFS of patients in real world.ResultsAmong the eligible 164 patients, 104 patients received olaparib and 60 patients received niraparib. 100 patients (61.0%) had mutations in breast cancer susceptibility gene (BRCA). 87 patients (53.0%) received primary debulking surgery (PDS) while 77 patients (47.0%) received interval debulking surgery (IDS). 94 patients (94/164, 57.3%) achieved R0 and 39 patients (23.8%) achieved R1 after PDS/IDS. 112 (68.3%) achieved complete response (CR) after first-line chemotherapy, while 49 (29.9%) achieved partial response (PR). The median follow-up time was 17.0 months (95% CI 15.6-18.4), and the median PFS has not been reached yet. Multivariate analysis demonstrated that BRCA mutations and CR/PR after platinum-based chemotherapy were independent factors associated with prolonged PFS. Hematologic toxicity was the most common grade≥3 AE. There were no incidence of myelodysplastic syndromes/acute myelogenous leukemia (MDS/AML).ConclusionFocusing on PARPi as first-line maintenance therapy for patients with EOC, this study represented the largest single-center real-world study in China to date. Two independent factors were identified to prolong the PFS of patients: BRCA mutated type and CR/PR after primary treatment, which should be further confirmed with long-term follow-up and large sample sizes

Structural characterization, physicochemical property, and antioxidant activity of polysaccharide components from Eucommia ulmoides leaves

Abstract Background Eucommia ulmoides (E. ulmoides) leaves are identified as a new resource of medicine and food homology. In this study, the structural characterization, physicochemical properties, and antioxidant activity of E. ulmoides polysaccharides (EUP) were studied. Results Three components with different molecular weights of 1.51 × 105 Da (EUP1), 3.05 × 104 Da (EUP2) and 1.17 × 105 Da (EUP3) were purified from E. ulmoides leaves. They were composed of l -rhamnose (Rha), d -arabinose (Ara), d -mannose (Man), d-glucose (Glu) and d -galactose (Gal), while EUP2 also contained small amounts of d -xylose (Xyl). Three components all had typical polysaccharides absorption peaks, which may be polysaccharides with β configuration of pyranose structure, and amorphous structure of acid polysaccharides with good thermal stability below 270 ℃. However, the molecular weight, monosaccharide composition and apparent morphology of the three components were different, resulting in a stronger scavenging ability of EUP2 and EUP3 against DPPH and OH free radicals. Conclusion The results will provide a theoretical reference for developing EUP-related foods and drugs. Graphical Abstrac

Low-density lipoprotein cholesterol and risk of hepatocellular carcinoma: a Mendelian randomization and mediation analysis

Abstract Background A previous study demonstrated that low-density lipoprotein cholesterol (LDL-C) is associated with hepatocellular carcinoma (HCC); however, the causality between them has not been proven due to conflicting research results and the interference of confounders. This study utilized Mendelian randomization (MR) to investigate the causal relationship between LDL-C and HCC and identify the mediating factors. Methods LDL-C, HCC, and coronary artery disease (CAD) genome-wide association study (GWAS) data were obtained from a public database. To investigate causality, inverse variance weighting (IVW) was the main analysis approach. MR‒Egger, simple mode, weighted median (WM), and weighted mode were employed as supplementary analytic methods. In addition, horizontal pleiotropy and heterogeneity were tested. To evaluate the stability of the MR results, a "leave-one-out" approach was used. Multivariate MR (MVMR) was utilized to correct the confounders that might affect causality, and mediation analysis was used to investigate the potential mediating effects. Finally, we used HCC risk to infer the reverse causality with LDL-C level. Results Random effects IVW results were (LDL-C-HCC: odds ratio (OR) = 0.703, 95% confidence interval (CI) = [0.508, 0.973], P = 0.034; CAD–HCC: OR = 0.722, 95% CI = [0.645, 0.808], P = 1.50 × 10–8; LDL-C–CAD: OR = 2.103, 95% CI = [1.862, 2.376], P = 5.65 × 10–33), demonstrating a causal link between LDL-C levels and a lower risk of HCC. Through MVMR, after mutual correction, the causal effect of LDL-C and CAD on HCC remained significant (P < 0.05). Through mediation analysis, it was proven that CAD mediated the causative connection between LDL-C and HCC, and the proportion of mediating effect on HCC was 58.52%. Reverse MR showed that HCC could affect LDL-C levels with a negative correlation (ORIVW = 0.979, 95% CI = [0.961, 0.997], P = 0.025). Conclusion This MR study confirmed the causal effect between LDL-C levels and HCC risk, with CAD playing a mediating role. It may provide a new view on HCC occurrence and development mechanisms, as well as new metabolic intervention targets for treatment

Bacteroides fragilis aggravates high-fat diet-induced non-alcoholic fatty liver disease by regulating lipid metabolism and remodeling gut microbiota

ABSTRACTGut microbiota dysbiosis is a prominent determinant that significantly contributes to the disruption of lipid metabolism. Consequently, it is essential to the occurrence and development of non-alcoholic fatty liver disease (NAFLD). Nevertheless, the connection between diet and symbiotic gut microbiota in the progression of NAFLD remains uncertain. The purpose of this study was to explore the role of supplementing commensal Bacteroides fragilis (B. fragilis) on lipid metabolism, gut microbiota, and metabolites in high-fat diet (HFD)-fed mice, elucidating the impact of gut microbiota and metabolites on the development of NAFLD. Our study revealed that supplementation with B. fragilis exacerbated both weight gain and obesity in mice. B. fragilis exacerbated blood glucose levels and liver dysfunction in mice. Furthermore, an increase in liver lipid accumulation and the upregulation of genes correlated with lipid metabolism were observed in mice. Under an HFD, supplementation of commensal B. fragilis resulted in alterations in the gut microbiota, notably a significant increase in Desulfovibrionaceae, which led to elevated endotoxin levels and thereby influenced the progression of NAFLD. It was interesting that the simultaneous examination of gut microbiota metabolites revealed a more pronounced impact of diet on short-chain fatty acids. This study represented the pioneering investigation into the impact of B. fragilis on NAFLD. Our findings demonstrated that B. fragilis induced dysregulation in the intestinal microbiota, leading to elevated levels of lipopolysaccharide and dysfunction in glucose and lipid metabolism, thereby exacerbating NAFLD.IMPORTANCESome intestinal symbiotic microbes are involved in the occurrence of the metabolic disorders. Our study investigated the impact of supplementing commensal Bacteroides fragilis on host metabolism in high-fat diet-fed mice. Research results indicated that adding a specific bacterial strain to the complex intestinal microecology can worsen metabolic conditions. This effect mainly affects the structural diversity of intestinal microorganisms, the increase in harmful bacteria in the gut, and the elevation of endotoxin levels, blood glucose, and lipid metabolism, thereby impacting the progression of non-alcoholic fatty liver disease (NAFLD). Understanding the principles that govern the establishment of microbial communities comprising multiple species is crucial for preventing or repairing dysfunctions in these communities, thereby enhancing host health and facilitating disease treatment. This study demonstrated that gut microbiota dysbiosis could contribute to metabolic dysfunction and provides new insights into how to promote gut microbiota in the prevention and therapy of NAFLD

Research Progress on Immune Checkpoint Inhibitors in Treatment of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related death, and most patients with HCC are diagnosed at an advanced stage. Before 2017, tyrosine kinase inhibitors were the main drugs for the treatment of advanced hepatocellular carcinoma. With the emergence of immune checkpoint inhibitors (ICIs), immunotherapy has gradually brought new hope to such patients. At present, the combination of ICIs and other systemic or local treatments has become a potential strategy for the treatment of advanced hepatocellular carcinoma, and some of these combinations have been included in large-scale clinical trials. The main challenges of immunotherapy for advanced hepatocellular carcinoma include the exploration of predictive biomarkers, management of immune-related adverse events, and exploration of effective combination regimens. This article provides the latest research progress on the single or combined use of ICIs and other immunotherapy for hepatocellular carcinoma and discusses the limitations of current research and clinical application and the future development direction

Multifunctional CuO-Coated Mesh for Wastewater Treatment

Funding Information: T.M. and J.Z. contributed equally to this work. The authors acknowledge the National Key R&D Program of China (No. 2017YFA0207202), the Natural Science Basic Research Plan in Shaanxi Province of China (No. 2021JM‐202 and 2019KJXX‐064), the Innovation Capability Support Program of Shaanxi (No. 2020TD‐024), the Program for Science & Technology Innovation Team of Shaanxi Province (No. 2018TD‐030) and the Fundamental Research Funds for the Central Universities (GK202002007), and the College Students’ Innovative Entrepreneurial Training Plan Program (S202010718079) for financial supports. B. Peng acknowledges the financial support from the Academy of Finland (No. 321443 and No. 328942). Publisher Copyright: © 2021 Wiley-VCH GmbHThe complex pollutants in wastewater including insoluble oils, organic dyes, and bacteria, have caused severe environmental problems, which are harmful to ecosystems and human health and are complex and difficult to achieve wastewater purification with one material or single procedure. Herein, a facile, yet environmentally benign strategy is proposed to fabricate a superhydrophilic/underwater superoleophobic CuO-coated mesh for all-in-one wastewater treatment. In this strategy, the hierarchical micro/nanostructured CuO-coated mesh is fabricated via an oxidation–dehydration process, which simultaneously endows the mesh with superwetting ability, remarkable photocatalytic degradation ability, and excellent photodynamic antibacterial activity. This CuO-coated mesh first exhibits the special underwater superoleophobicity, superior durability, reusability, and high antifouling capability, which ensures its high separation efficiency for oil/water mixtures. Then, this CuO-coated mesh is underwater superoleophobic, possessing the remarkable photocatalytic degradation performance of organic dye contaminates in water and excellent photodynamic antibacterial activities against Escherichia coli and Staphylococcus aureus under visible-light irradiation. As such, it plays a multi-role in wastewater remedy, significantly simplifying the implementation and saving the cost in practice. This work suggests a promising approach for the design of multi-functional materials in environmental remedies.Peer reviewe

Comprehensive analysis of basement membrane and immune checkpoint related lncRNA and its prognostic value in hepatocellular carcinoma via machine learning

Background: Hepatocellular carcinoma (HCC), which is characterized by its high malignancy, generally exhibits poor response to immunotherapy. As part of the tumor microenvironment, basement membranes (BMs) are involved in tumor development and immune activities. Presently, there is no integrated analysis linking the basement membrane with immune checkpoints, especially from the perspective of lncRNA. Methods: Based on transcriptome data from The Cancer Genome Atlas, BMs-related and immune checkpoint-related lncRNAs were identified. By applying univariable Cox regression and Machine learning (LASSO and SVM-RFE algorithm), a 10-lncRNA prognosis signature was constructed. The prognostic significance of this signature was assessed by survival analysis. GSEA, ssGSEA, and drug sensitivity analysis were conducted to investigate potential functional pathways, immune status, and clinical implications of guiding individual treatments in HCC. Finally, the promoting migration effect of LINC01224 was validated via in vitro experiments. Results: The multiple Cox regression, receiver operating characteristic curves, and stratified survival analysis of clinical subgroups exhibited the robust prognostic ability of the lncRNA signature. Results of the GSEA and drug sensitivity analysis revealed significant differences in potential functional pathways and response to drugs between the two risk groups. In addition, the risk level of HCC patients was distinctly correlated with immune cell infiltration status. More importantly, LINC01224 was independently associated with the OS of HCC patients (P < 0.05), suppressing the expression of LINC01224 inhibited the migration of HCC cells. Conclusion: This study developed a reliable signature for the prognosis of HCC based on BM and immune checkpoint related lncRNA, revealing that LINC01224 might be a prognostic biomarker for HCC associated with the progression of HCC

An Innovative Approach for Improving the Accuracy of Digital Elevation Models for Cultivated Land

The redistribution of solar radiation, temperature, soil moisture and heat by topography affects the physical and chemical properties of the soil and the spatial distribution characteristics of crop growth. Analyses of the relationship between topography and these variables may help to improve the accuracy of digital elevation models (DEMs). The purpose of correcting Shuttle Radar Topography Mission (SRTM) data is to obtain high-precision DEM data in cultivated land. A typical black soil area was studied. A high-precision reference DEM was generated from an unmanned aerial vehicle (UAV) and extensive measured ground elevation data. The normalized differential vegetation index (NDVI), perpendicular drought index (PDI) extracted from SPOT-6 remote sensing images and potential solar radiation (PSR) extracted from SRTM. The interactions between topography and NDVI, PDI, and PSR were analyzed. The NDVI, PDI and PSR in June, July, August and September of 2016 and the SRTM were used as independent variables, and the UAV DEM was used as the dependent variable. Linear stepwise regression (LSR) and a back-propagation neural network (BPNN) were used to establish an elevation prediction model. The results indicated that (1) The correlation between topography and NDVI, PSR, PDI was significant at 0.01 level. The PDI and PSR improved the spatial resolution of SRTM data and reduce the vertical error. (2) The BPNN (R21 = 0.98, root mean square error, RMSE1 = 0.54) yielded a higher SRTM accuracy than did the studied linear model (RMSE1 = 1.00, R21 = 0.90). (3) A series of significant improvements in the SRTM were observed when assessed with the reference DEMs for two different areas, with RMSE reductions of 91% (from 14.95 m to 1.23 m) and 93% (from 15.6 m to 0.94 m). The proposed method improved the accuracy of existing DEMs and could provide support for accurate farmland management