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Objective This study was performed to investigate the role of probiotics (Clostridium butyricum combined with Bifidobacterium infantis) in the treatment of minimal hepatic encephalopathy (MHE) in patients with hepatitis B virus (HBV)-induced liver cirrhosis. Methods Sixty-seven consecutive patients with HBV-induced cirrhosis without overt hepatic encephalopathy were screened using the number connection test and digit symbol test. The patients were randomized to receive probiotics (n = 30) or no probiotics (n = 37) for 3 months. At the end of the trial, changes in cognition, intestinal microbiota, venous ammonia, and intestinal mucosal barriers were analyzed using recommended systems biology techniques. Results The patients’ cognition was significantly improved after probiotic treatment. The predominant bacteria (Clostridium cluster I and Bifidobacterium) were significantly enriched in the probiotics-treated group, while Enterococcus and Enterobacteriaceae were significantly decreased. Probiotic treatment was also associated with an obvious reduction in venous ammonia. Additionally, the parameters of the intestinal mucosal barrier were obviously improved after probiotic treatment, which might have contributed to the improved cognition and the decreased ammonia levels. Conclusion Treatment with probiotics containing C. butyricum and B. infantis represents a new adjuvant therapy for the management of MHE in patients with HBV-induced cirrhosis.

The extracellular matrix (ECM) is a significant constituent of tumors, fulfilling various essential functions such as providing mechanical support, influencing the microenvironment, and serving as a reservoir for signaling molecules. The abundance and degree of cross-linking of ECM components are critical determinants of tissue stiffness. In the process of tumorigenesis, the interaction between ECM and immune cells within the tumor microenvironment (TME) frequently leads to ECM stiffness, thereby disrupting normal mechanotransduction and promoting malignant progression. Therefore, acquiring a thorough comprehension of the dysregulation of ECM within the TME would significantly aid in the identification of potential therapeutic targets for cancer treatment. In this regard, we have compiled a comprehensive summary encompassing the following aspects: (1) the principal components of ECM and their roles in malignant conditions; (2) the intricate interaction between ECM and immune cells within the TME; and (3) the pivotal regulators governing the onco-immune response in ECM.

Haploinsufficiency of A20 (HA20) is a newly described immune dysregulation disease due to the loss-of-function mutation in TNFAIP3. In the present study, we report six patients from four unrelated Chinese families with distinct pathogenic mutations in TNFAIP3, including three novel variants. All of the patients presented with early-onset autoimmune/auto-inflammatory diseases, including Crohn’s disease, Behcet’s disease, systemic lupus erythematosus, and unclassified auto-inflammatory syndrome. Immunological phenotype tests showed elevated levels of serum pro-inflammatory cytokines, reduced naïve B cells and TFH cells, an inverted CD4:CD8 ratio, and increased susceptibility to restimulation-induced cell death (RICD) and FASL-induced apoptosis in derived T cells. Insufficient expression of A20 was found in these patients. A20 truncated protein was detected in mutant-transfected 293T cells. Upon TNF-α stimulation, the NF-κB pathway was over-activated in both derived T cells of these patients and mutant-transfected Hela cells. In conclusion, clinical manifestations are diverse in patients with HA20, even in those with the same TNFAIP3 mutation. A20 inhibits the NF-κB pathway and plays a crucial role in the regulation of cell death. Haploinsufficiency of A20 leads to defects in both innate and adaptive immunity.

The involvement of circular RNAs (circRNAs) in the progression of diabetic nephropathy (DN) has been reported. However, the functions of circ_0060077 in DN remain unclear. HK-2 cells were treated with high glucose (HG) to establish DN cell model. Quantitative real-time polymerase chain reaction (qRT-PCR) was proceeded to determine the levels of circ_0060077, microRNA-145-5p (miR-145-5p) and vasorin (VASN). Cell counting kit-8 (CCK-8) assay, 5-ethynyl-2’-deoxyuridine (EdU) assay and colony formation assay were conducted to assess cell proliferation ability. Flow cytometry analysis was employed for cell apoptosis. The oxidative stress level was evaluated by commercial kits. Enzyme-linked immunosorbent assay (ELISA) was adopted to examine the concentrations of inflammatory factors. Western blot assay was utilized for protein levels. Dual-luciferase reporter assay and RNA pull-down assay were manipulated to analyze the relationships among circ_0060077, miR-145-5p and VASN. Circ_0060077 level was increased in DN patients and HG-stimulated HK-2 cells. Circ_0060077 knockdown ameliorated the inhibitory effect of HG on HK-2 cell proliferation and the promotional effects on cell apoptosis, oxidative stress, inflammation and fibrosis. MiR-145-5p was identified as the target for circ_0060077 and miR-145-5p inhibition ameliorated the effect of circ_0060077 silencing on HG-induced HK-2 cell injury. Moreover, miR-145-5p directly bound to VASN. Overexpression of miR-145-5p facilitated cell proliferation and repressed apoptosis, oxidative injury, inflammation and fibrosis in HG-induced HK-2 cells by targeting VASN. Circ_0060077 silencing protected HK-2 cells from HG-induced damage by regulating miR-145-5p/VASN axis.

Species of the brown algae of the genus Dictyota are rich sources of bioactive secondary metabolites with diverse structural features. Excellent progress has been made in the discovery of diterpenes possessing broad chemical defensive activities from this genus. Most of these diterpenes exhibit significant biological activities, such as antiviral, cytotoxic and chemical defensive activities. In the present review, we summarized diterpenes isolated from the brown algae of the genus.

Aristolochic acid (AA), mainly derived from herbal and plants, was listed as a human carcinogen class I in 2002. Aristolochic acid nephropathy (AAN) is a rapidly progressive tubulointerstitial nephritis and urothelial cancer caused by AA. However, the targeting molecular mechanisms of AAs-induced nephrotoxicity are largely unclear. This study aims to dissect targeting molecular mechanisms of AA-induced nephrotoxicity. Activity-based protein profiling (ABPP) in combination with cellular thermal shift assay (CETSA) was performed to identify the AAs binding target proteins. Our data indicated that several key enzymes in the metabolic process and mitochondrial respiration including IDH2 and MDH2 (Krebs cycle), PKM and LDH (aerobic respiration), FASN (fatty acid beta-oxidation), HK2 (glucose metabolism), and ATP synthase were identified as directly binding targets of AAs. Metabolomics and oxygen consumption rate (OCR) experiments further confirmed that AAs targeting proteins disrupted metabolic biosynthesis processes and impaired mitochondrial functions. Ultimately, AAs induced renal cells apoptosis by disturbing various biological processes. Cumulatively, AAs may directly bind to key proteins involved in the metabolic process and mitochondrial homeostasis, and finally induce aristolochic acid nephropathy. Our findings provide novel insight into underlying mechanisms of AAs-induced kidney toxicity, which may help to develop therapeutic strategies for AAN.

Alkali-activated cementitious materials are environmentally friendly alternatives to traditional cement. The structure of their core product, sodium aluminosilicate hydrate (N-A-S-H) gel, is regulated by the silicon-to-aluminum (Si/Al) ratio; however, the atomic-scale mechanism underlying this influence remains unclear. Integrating reactive force field molecular dynamics simulations and experiments, this study systematically reveals the regulation mechanism of the Si/Al ratio (1.0–2.0) on the microstructure and macroscopic properties of N-A-S-H gels. Starting from well-defined PS and PSS oligomers, the simulation results demonstrate that the Si/Al ratio governs the polymerization pathway, aluminum coordination environment (especially the content of pentacoordinate aluminum), and evolution of nanoporosity. When the Si/Al ratio is approximately 1.8, the system exhibits the highest silicate polymerization degree, lowest nanoporosity, and densest three-dimensional (3D) network structure; deviation from this ratio leads to structural degradation due to charge imbalance or excessive polymerization. These computational findings are validated by experiments on fly ash-based geopolymers: the material achieves the highest compressive strength at a Si/Al ratio of 1.8. The consistency between simulations and experiments collectively reveals a cross-scale action mechanism: the Si/Al ratio determines the macroscopic mechanical properties by regulating the nanoscale packing density and defect distribution of the gel. This study provides critical atomic-scale insights for the rational design of high-performance geopolymers.

Severe haze events during which particulate matter (PM) increases quickly from tens to hundreds of microgram per cubic meter in 1–2 days frequently occur in China. Although it has been known that PM is influenced by complex interplays among emissions, meteorology, and physical and chemical processes, specific mechanisms remain elusive. Here, a new positive feedback mechanism between planetary boundary layer (PBL), relative humidity (RH), and secondary PM (SPM) formation is proposed based on a comprehensive field experiment and model simulation. The decreased PBL associated with increased PM increases RH by weakening the vertical transport of water vapor; the increased RH in turn enhances the SPM formation through heterogeneous aqueous reactions, which further enhances PM, weakens solar radiation, and decreases PBL height. This positive feedback, together with the PM-Radiation-PBL feedback, constitutes a key mechanism that links PM, radiation, PBL properties (e.g. PBL height and RH), and SPM formation, This mechanism is self-amplifying, leading to faster PM production, accumulation, and more severe haze pollution.

Background The mammal intestinal microbiota is involved in various physiological processes and plays a key role in host environment adaption. However, for non-human primates (NHPs), little is known about their gut microbial community in high-altitude environments and even less about their adaption to such habitats. We characterised the gut microbial community of rhesus macaques from multiple high-altitude environments and compared it to those of low-altitude populations. Results We collected faecal samples of rhesus macaques from four high-altitude populations (above 3000 m) and three low-altitude populations (below 500 m). By calculating the alpha diversity index, we found that high-altitude populations exhibited a higher diversity. Statistical analysis of beta diversity indicated significant differences between high- and low-altitude populations. Significant differences were also detected at the phylum and family levels. At the phylum level, the high-altitude gut microbial community was dominated by Firmicutes (63.42%), while at low altitudes, it was dominated by Bacteroidetes (47.4%). At the family level, the high-altitude population was dominated by Ruminococcaceae (36.2%), while the low-altitude one was dominated by Prevotellaceae (39.6%). Some families, such as Christensenellaceae and Rikenellaceae, were consistently higher abundant in all high-altitude populations. We analysed the overlap of operational taxonomic units (OTUs) in high-altitude populations and determined their core OTUs (shared by all four high-altitude populations). However, when compared with the low-altitude core OTUs, only 65% were shared, suggesting a divergence in core OTUs. Function prediction indicated a significant difference in gene copy number of 35 level-2 pathways between high- and low-altitude populations; 29 of them were higher in high altitudes, especially in membrane transport and carbohydrate metabolism. Conclusions The gut microbial community of high-altitude rhesus macaques was significantly distinct from that of low-altitude populations in terms of diversity, composition and function. High-altitude populations were dominated by Firmicutes and Ruminococcace, while in low-altitude populations, Bacteroidetes and Prevotellaceae were dominant. The difference in gut microbiota between these two populations may be caused by differences in host diet, environmental temperature and oxygen pressure. These differentiated gut microbial microorganisms may play a critical role in the adaptive evolution of rhesus macaques to high-altitude environments.

Purpose The personalized setting of plan parameters in the Auto‐Planning module of the Pinnacle treatment planning system (TPS) using the PlanIQ feasibility tool was evaluated for lung cancer conventional fractionated radiotherapy (CFRT). Materials and method We reviewed the records of ten patients with lung cancer who were treated with volumetric modulated arc therapy (VMAT). Three plans were designed for each patient: the clinically accepted manual plan (MP) and two automatic plans including one generated using the generic plan parameters in technique script (AP1) and the other generated using personalized plan parameters derived based on feasibility dose volume histogram (FDVH) in PlanIQ (AP2). The plans were assessed according to the dosimetric parameters, monitor units, and planning time. A plan quality metric (PQM) was defined according to the clinical requirements for plan assessment. Results AP2 achieved better lung sparing than AP1 and MP. The PQM value of AP2 (52.5 ± 14.3) was higher than those of AP1 (49.2 ± 16.2) and MP (44.8 ± 16.9) with P < 0.05. The monitor units of AP2 (585.9 ± 142.9 MU) was higher than that of AP1 (511.1 ± 136.5 MU) and lower than that of MP (632.8 ± 143.8 MU) with p < 0.05. The planning time of AP2 (33.2 ± 4.8 min) was slightly higher than that of AP1 (28.2 ± 4.0 min) and substantially lower than that of MP (72.9 ± 28.5 min) with P < 0.05. Conclusions The Auto‐Planning module of the Pinnacle system using personalized plan parameters suggested by the PlanIQ Feasibility tool provides superior quality for lung cancer plans, especially in terms of lung sparing. The time consumption of Auto‐Planning was slightly higher with the personalized parameters compared to that with the generic parameters, but significantly lower than that for the manual plan.