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, a botanical drug derived from the dried rhizome of Coptis species (e.g., ), is characterized by abundant natural sources, significant bioactivity, and high safety. It holds considerable potential for translational applications in metabolic diseases, particularly in ameliorating type 2 diabetes mellitus (T2DM)-related metabolic dysfunction-associated steatohepatitis (MASH). However, mechanistic studies on remain limited. This study aimed to evaluate the therapeutic effects of on hepatic histological and functional damage, metabolic disorders, and insulin resistance in T2DM-related MASH and investigate its underlying mechanisms. Two-day-old male C57BL/6J mice were subcutaneously injected with streptozotocin (200 μg/20 μL per mouse). At 4 weeks of age, the mice were weaned and switched to a high-fat diet until week 9 to induce T2DM-related MASH. Starting from week 5, decoction was administered via oral gavage for four consecutive weeks to conduct studies. Additionally, hepatocytes were isolated from the model mice and exposed to epiberberine, the active metabolite of , for cellular-level investigations. significantly attenuated hepatic inflammatory lesions, reduced the non-alcoholic fatty liver disease activity score, improved liver function, and alleviated glucose and lipid metabolism disorders and insulin resistance in a dose-dependent manner in T2DM-related MASH mice. At the transcriptional level, key components of the interleukin-17 receptor A (IL-17RA)/nuclear factor kappa B (NF-κB) signaling pathway were upregulated in the hepatocytes of T2DM-related MASH mice, and both and epiberberine downregulated their expressions. Furthermore, and epiberberine suppressed the secretion of pro-inflammatory cytokines associated with the IL-17RA/NF-κB pathway in hepatocytes. ameliorates pathological phenotypes in T2DM-related MASH by inhibiting the IL-17RA/NF-κB signaling pathway, and its active metabolite epiberberine is involved in mediating these protective effects.

This study was to investigate the clinical characteristics and laboratory parameters of severe fever with thrombocytopenia syndrome (SFTS). A detailed retrospective analysis of clinical records for SFTS patients was conducted. Fifty-one cases confirmed SFTS virus infected were enrolled. The clinical characteristics and laboratory parameters between survivors and non-survivors were analyzed. All patients aged between 30 and 80 years were farmers or residing in wooded and hilly areas. All patients occurred between April and October. The major clinical manifestations were fever, fatigue, diarrhea, myalgia, nausea and vomiting. Conscious disturbance, lymph node enlargement and hemorrhage were common. Fatal outcome occurred in 31.4% (16/51) of patients. Compared with survivors group, in non-survivors group, the proportion of consciousness disturbance, age, the levels of AST, LDH, Bun, Cr, PT and APTT were significantly increased, and PLT was significantly decreased. The age, PLT, AST, LDH, Cr, PT and APTT were the risk factors for fatal outcomes. Moreover, the age (OR, 1.245; 95% CI, 1.052-1.474) and APTT (OR, 1.095; 95% CI, 1.005-1.192) were the independent risk factors for fatal outcomes. Heteromorphic lymphocyte and hemophagocytosis could be found in SFTS patients, especially the proportion of finding hemophagocytosis was significantly higher in non-survivors group compared with survivors group. These results suggest SFTS is a systemic infection, the age and APTT can be used as potential predictors referring to severe SFTS cases.

ObjectivesFamilies that contain multiple siblings affected with childhood-onset of systemic lupus erythematosus (SLE) likely have strong genetic predispositions. We performed whole-exome sequencing (WES) to identify familial rare risk variants and to assess their effects in lupus.MethodsSanger sequencing validated the two ultra-rare, predicted pathogenic risk variants discovered by WES and identified additional variants in 562 additional SLE patients. Effects of a splice site variant and a frameshift variant were assessed using a Minigene assay and CRISPR/Cas9-mediated knock-in (KI) mice, respectively.ResultsThe two familial ultra-rare, predicted loss-of-function (LOF) SAT1 variants exhibited X-linked recessive Mendelian inheritance in two unrelated African-American families. Each LOF variant was transmitted from the heterozygous unaffected mother to her two sons with childhood-onset SLE. The p.Asp40Tyr variant affected a splice donor site causing deleterious transcripts. The young hemizygous male and homozygous female Sat1p.Glu92Leufs*6 KI mice spontaneously developed splenomegaly, enlarged glomeruli with leukocyte infiltration, proteinuria and elevated expression of type I interferon inducible genes. SAT1 is highly expressed in neutrophils and encodes spermidine/spermine-N1-acetyltransferase 1 (SSAT1), a rate-limiting enzyme in polyamine catabolism. Young male KI mice exhibited neutrophil defects and decreased proportions of Foxp3+CD4+ T-cell subsets. Circulating neutrophil counts and proportions of Foxp3+CD4+ T cells correlated with decreased plasma levels of spermine in treatment naïve, incipient SLE patients.ConclusionsWe identified two novel SAT1 loss-of-function variants, showed the ability of the frameshift variant to confer murine lupus, highlighted the pathogenic role of dysregulated polyamine catabolism, and identified SAT1 LOF variants as new monogenic causes for SLE.

ObjectivesFamilies that contain multiple siblings affected with childhood onset of systemic lupus erythematosus (SLE) likely have strong genetic predispositions. We performed whole exome sequencing (WES) to identify familial rare risk variants and to assess their effects in lupus.MethodsSanger sequencing validated the two ultra-rare, predicted pathogenic risk variants discovered by WES and identified additional variants in 562 additional patients with SLE. Effects of a splice site variant and a frameshift variant were assessed using a Minigene assay and CRISPR/Cas9-mediated knock-in (KI) mice, respectively.ResultsThe two familial ultra-rare, predicted loss-of-function (LOF) SAT1 variants exhibited X-linked recessive Mendelian inheritance in two unrelated African–American families. Each LOF variant was transmitted from the heterozygous unaffected mother to her two sons with childhood-onset SLE. The p.Asp40Tyr variant affected a splice donor site causing deleterious transcripts. The young hemizygous male and homozygous female Sat1 p.Glu92Leufs*6 KI mice spontaneously developed splenomegaly, enlarged glomeruli with leucocyte infiltration, proteinuria and elevated expression of type I interferon-inducible genes. SAT1 is highly expressed in neutrophils and encodes spermidine/spermine-N1-acetyltransferase 1 (SSAT1), a rate-limiting enzyme in polyamine catabolism. Young male KI mice exhibited neutrophil defects and decreased proportions of Foxp3 +CD4+ T-cell subsets. Circulating neutrophil counts and proportions of Foxp3 +CD4+ T cells correlated with decreased plasma levels of spermine in treatment-naive, incipient SLE patients.ConclusionsWe identified two novel SAT1 LOF variants, showed the ability of the frameshift variant to confer murine lupus, highlighted the pathogenic role of dysregulated polyamine catabolism and identified SAT1 LOF variants as new monogenic causes for SLE.

慢性肝病是指肝脏因长期受到各种损伤，出现持续时间超过6个月且不可逆性病理改变的疾病。大黄素 (EMO) 是一种来源于大黄的天然蒽醌衍生物，其药理作用已被广泛研究，表现出多种生物特性并涉及多个信号分子和途径。目前针对慢性肝病的治疗方案以西药或手术治疗为主，由于副作用、高成本等多种原因，治疗推进受限。EMO因其天然来源和疗效，在治疗慢性肝病方面具有独特的优势，现已成为研究热点。本文通过总结梳理EMO对慢性肝病的治疗作用并探讨其机制，以期为慢性肝病的中医药治疗与临床药物研发提供一定的科学依据。

Acute lung injury (ALI) is a severe clinical disease marked by dysregulated inflammation response and has a high rate of morbidity and mortality. Macrophages, which play diverse roles in the inflammatory response, are becoming therapeutic targets in ALI. In this study we investigated the effects of dehydrocostus lactone (DHL), a natural sesquiterpene, on macrophage activation and LPS-induced ALI. The macrophage cell line RAW264.7 and primary lung macrophages were incubated with DHL (0, 3, 5, 10 and 30 μmol/L) for 0.5 h and then challenged with LPS (100 ng/mL) for up to 8 hours. C57BL/6 mice were intratracheally injected with LPS (5 mg/kg) to induce acute lung injury (ALI) and then treated with a range of DHL doses intraperitoneally (5 to 20 mg/kg). The results showed that DHL inhibited LPS-induced production of proinflammatory mediators such as iNOS, NO, and cytokines including TNF-α, IL-6, IL-1β, and IL-12 p35 by suppressing the activity of NF-κB via p38 MAPK/MK2 and Akt signaling pathway in macrophages. The in vivo results revealed that DHL significantly attenuated LPS-induced pathological injury and reduced cytokines expression in the lung. NF-κB, p38 MAPK/MK2 and Akt signaling molecules were also involved in the anti-inflammatory effect. Collectively, our findings suggested that DHL is a promising agent for alleviating LPS-induced ALI.

The ocular lubrication, where the eyelid constantly slides on the curved corneal surface, is considered as one of primary lubrication systems in bio-tribology. Under reliable lubrication conditions, sensitive ocular tissues remain intact from fatigue damage during spontaneous blink cycles. The tear film, evenly filled between cornea and conjunctiva, is a biological fluid with dynamic adjustment ability, which provides superior lubrication with the friction coefficient of below 0.01. However, the lubrication failure may result in a variety of uncomfortable symptoms such as inflammatory reactions, tissue damage and neurological abnormalities. Therefore, it is essential to clarify the fundamental mechanism of ocular lubrication, which helps to alleviate and even recover from various ocular symptoms. This review firstly demonstrates that the ocular components, containing lipids and mucins, contribute to maintaining the lubrication stability of tear film. Furthermore, the ocular lubrication state in various physiological environments and the physical effect on tear film dynamics are further discussed. As typical applications, the therapeutic agents of dry eye syndrome and contact lens with superior lubrication effects are introduced and their lubrication mechanisms are clarified. Finally, this review summarizes a series of the latest research inspired by ocular lubrication. Overall, this work will provide a valuable guidance on the theoretical research and extensive applications in the field of biological lubrication.

Background The gut microbiota of the giant panda ( Ailuropoda melanoleuca ), a global symbol of conservation, are believed to be involved in the host’s dietary switch to a fibrous bamboo diet. However, their exact roles are still largely unknown. Results In this study, we first comprehensively analyzed a large number of gut metagenomes giant pandas ( n  = 322), including 98 pandas sequenced in this study with deep sequencing (Illumina) and third-generation sequencing (nanopore). We reconstructed 408 metagenome-assembled genomes (MAGs), and 148 of which (36.27%) were near complete. The most abundant MAG was classified as Streptococcus alactolyticus . A pairwise comparison of the metagenomes and meta-transcriptomes in 14 feces revealed genes involved in carbohydrate metabolism were lower, but those involved in protein metabolism were greater in abundance and expression in giant pandas compared to those in herbivores and omnivores. Of note, S. alactolyticus was positively correlated to the KEGG modules of essential amino-acid biosynthesis. After being isolated from pandas and gavaged to mice, S. alactolyticus significantly increased the relative abundance of essential amino acids in mice jejunum. Conclusions The study highlights the unique protein metabolic profiles in the giant panda’s gut microbiome. The findings suggest that S. alactolyticus is an important player in the gut microbiota that contributes to the giant panda’s dietary adaptation by more involvement in protein rather than carbohydrate metabolism. 4zh5Ny6QmwZifdgaSCFmHg Video Abstract

Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease where macrophages drive fibrogenesis, yet Hdac11’s role is unclear. We first identify pronounced Hdac11 upregulation in IPF lungs, which is associated with an enrichment in alveolar macrophages (AMs). Genetic ablation of Hdac11 or adoptive transfer of Hdac11-deficient macrophages markedly attenuates fibrosis. Specifically, Hdac11 deficiency significantly reduces M2 macrophage polarization in vivo and vitro and is associated with reduced macrophage-myofibroblast transition (MMT) like phenotypic reprogramming, thereby decreasing myofibroblast accumulation and profibrotic gene expression. Mechanistically, impaired mitophagy mediates Hdac11-mediated M2 macrophage polarization and is associated with MMT-like changes. Hdac11 regulates mitochondrial quality control by deacetylating Parkin at lysine 76, promoting its ubiquitination and degradation, which impairs mitophagy and drives profibrotic macrophage activation. Pharmacological Hdac11 inhibition effectively reverses bleomycin-induced fibrosis. Taken together, our work identifies Hdac11 as a target of Parkin-mediated mitophagy in macrophages, establishing Hdac11-Parkin axis disruption as an important mechanism in IPF and highlighting Hdac11 inhibition as a potential therapeutic strategy. Epigenetic dysregulation is a central driver of the progressive remodeling seen in idiopathic pulmonary fibrosis with specific factors to be further explored. The authors here show Hdac11 drives lung fibrosis by repressing Parkin-dependent mitophagy, which is associated with enhanced macrophage M2-type polarization and myofibroblast trans-differentiation.

The turbulent thermal dynamics and mixing performance of kenics static mixer (KSM), lightnin static mixer (LSM) and Q-type static mixer (QSM) were numerically simulated with uniform heat flux within the range of Reynolds numbers (Re) between 6000 and 30000. The numerical predictions of Nusselt number (Nu) and friction coefficient (f) in KSM were well consistent with the experimental data. The dean vortices, thermal resistance, entropy generation and field synergy were fully analyzed to obtain the enhancement mechanism of heat transfer performance. The synergy performance between temperature gradient and flow field firstly decreased and then increased and are superior to that of KSM with increasing Re. With the same Re, the entropy generation rates of LSM are 0.93–0.94 times that of QSM. LSM is a better alternative consideration for convection mixing and heat transfer enhancement. Two new relationships between Nu and f under different dimensionless uniform heat flux are obtained.