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To systematically summarize the published literature on the genetic variants associated with nonalcoholic fatty liver disease (NAFLD). Literature from Web of Science, PubMed, and Embase between January 1980 and September 2022 was systematically searched. Meta-analyses of the genetic variants were conducted using at least five data sources. The epidemiologic credibility of the significant associations was graded using the Venice criteria. Based on literature screening, 399 eligible studies were included, comprising 381 candidate gene association, 16 genome-wide association, and 2 whole-exome sequencing studies. We identified 465 genetic variants in 173 genes in candidate gene association studies, and 25 genetic variants in 17 genes were included in the meta-analysis. The meta-analysis identified 11 variants in 10 genes that were significantly associated with NAFLD, with cumulative epidemiological evidence of an association graded as strong for two variants in two genes (HFE, TNF), moderate for four variants in three genes (TM6SF2, GCKR, and ADIPOQ), and weak for five variants in five genes (MBOAT7, PEMT, PNPLA3, LEPR, and MTHFR). This study identified six variants in five genes that had moderate to strong evidence of an association with NAFLD, which may help understand the genetic architecture of NAFLD risk. [ABSTRACT FROM AUTHOR]

• Active compounds in BGN successfully identified firstly. • UPLC-HRMS detection of substances in BGN for serum pharmacology, not database. • Stable binding of core components and essential targets were predicted and validated completely. • Anti-hepatic fibrotic efficiency of BGN decoction, drug-containing serum and core components were confirmed in vivo (mice and zebrafish) and in vitro. Early intervention in hepatic fibrosis (HF) is critical to reducing the risk of cirrhosis-related mortality and hepatocellular cancer. However, treating fibrosis has proven to be more challenging, with no approved anti-fibrotic therapies currently available for HF. Traditional Chinese medicines (TCMs) hold significant potential for the management of HF. This study aims to propose a systematic approach for investigating the pharmacological basis of Baoganning (BGN) Decoction, providing empirical evidence to support future research on its targets and mechanisms of BGN. Ultrahigh-performance liquid chromatography coupled with high- resolution mass spectrometry (UPLC-HRMS) was employed to analyze the chemical composition of BGN. Key compounds were investigated using disease databases to predict relevant targets, followed by molecular docking and molecular dynamics simulations to explore molecular-level interactions. The efficacy and critical targets of BGN were validated through in vivo and in vitro experiments. UPLC-HRMS was used to identify the chemical composition of the BGN, and serum pharmacology determined the active chemical constituents in rat plasma. Zebrafish, HSC-T6 cells, JS-1 cell line and mice served as experimental models to evaluate the antifibrotic effects of BGN. BGN demonstrated significant antifibrotic effect in vivo and in vitro models. A total of 757 compounds were identified in BGN, with 18 prototypical components and metabolites detected. Three compounds-quillaic acid, methyl cholate, and 3 β -hydroxy-5-cholenoic exhibited dose-dependent inhibitory effects on HF. Molecular docking studies revealed stable interactions between these compounds and predicted targets. Additionally, the screened components effectively reduced the expression of ‌α-SMA and COL-I in both a cellular model and a zebrafish fibrosis model in a dose-dependent manner. The comprehensive analysis of BGN's chemical composition and its metabolic processes provides valuable insights into its pharmacological effects. These findings support the potential clinical and international application of BGN in treating hepatic fibrosis and improving patient outcomes. [ABSTRACT FROM AUTHOR]

Senecavirus A (SVA) is a causative agent that can cause vesicular disease in swine, which causes a great threat to the swine husbandry in the world. Therefore, it is necessary to develop a vaccine that can effectively prevent the spread of SVA. In this study, we developed a 24-polymeric nano-scaffold using β-annulus peptide from tomato bushy effect virus (TBSV) by coupling this antigen to SVA B cell epitope VP1 21–26 and VP2 proteins via linkers, respectively. The SVA-based nanoparticle protein of the VP1(B)- β- VP2 was expressed and purified by low-cost prokaryotic system to prepare a SVA nanoparticle vaccine. The immunological protective effect of SVA nanoparticle vaccine was evaluated in mouse and swine models, respectively. The results suggested that both mice and swine could induce high levels SVA neutralizing antibodies and IgG antibodies after two doses immunization. In addition, the swine challenge protection experiment showed that the protection rate of immune SVA nanoparticle vaccine and SVA inactivated vaccine both were 80 %, while the negative control had no protection effect. It demonstrated that SVA nanoparticle vaccine effectively prevented SVA infection in swine. In summary, the preparation of SVA vaccine by using β-annulus peptide is a promising candidate vaccine for prevent SVA transmission, and provides a new idea for the development of novel SVA vaccines. • A SVA nanoparticle vaccine was constructed using a 24-polymeric nano-scaffold composed of β-annulus peptide derived from the tomato bushy stunt virus (TBSV), conjugated with SVA B cell epitope VP1 21–26 and VP2 proteins. • The β-annulus peptide serves as an antigen delivery system capable of carrying SVA antigens, forming ordered assemblies that trigger robust adaptive immune responses and promote durable protective immunity, thereby availably controlling and eliminating SVA infection. • The SVA nanoparticle vaccine induced swine to generate high titers of neutralizing antibodies and promoted biased Th1-type cellular immune responses, effectively clearing the virus and reducing swine morbidity. [ABSTRACT FROM AUTHOR]

Gold nanoparticles (AuNPs)-based immunochromatographic assay has gained popularity as a rapid detection method for food hazards. Synthesizing highly stable AuNPs in a rapid, simple and environmentally friendly manner is a key focus in this field. Here, we present a green microfluidic strategy for the rapid, automated, and size-controllable synthesis of pepsin-doped AuNPs (AuNPs@Pep) by employing glucose-pepsin as a versatile reducing agent and stabilizer. Through combining the colorimetric and photothermal (PoT) properties of AuNPs@Pep, both "signal-off" and "signal-on" formats of microfluidic paper analytical devices (PADs) were developed for detection of a small molecule antibiotic, florfenicol, and an egg allergen, ovalbumin. Compared to the colorimetric mode, a 4-fold and 3-fold improvement in limit of detection was observed in the "signal-off" detection of florfenicol and the "signal-on" detection of ovalbumin, respectively. The results demonstrated the practicality of AuNPs@Pep as a colorimetric/PoT dual-readout probe for immunochromatographic detection of food hazards at different molecular scales. [Display omitted] • Rapid and size-controlled green synthesis of AuNPs@Pep on a microfluidic device. • AuNPs@Pep has excellent biosensing stability as a colorimetric/photothermal probe. • High-performance "signal-on" and "signal-off" dual-readout PADs for food hazards. [ABSTRACT FROM AUTHOR]

Despite the success of anti-programmed cell death-1 (anti-PD-1) immunotherapy, many cancer patients remain unresponsive, and reliable predictive biomarkers are lacking. Here, we show that aberrant expression of the pyrimidinergic receptor P2RY6 is frequent in human cancers and causes immune evasion. In mouse syngeneic and human xenograft tumor models, ectopic expression of P2RY6 shapes an immunosuppressive tumor microenvironment (TME) to enhance tumor growth and resistance to immunotherapy, whereas deletion of P2RY6 from tumors with high P2RY6 expression inflames the TME to inhibit tumor growth. As a G protein-coupled receptor, P2RY6 activates Gq/phospholipase C-β signaling and stimulates the synthesis of prostaglandin E2, which is a key mediator of immunosuppression in the TME. In contrast to the essential role of P2RY6 in tumors, global deletion of P2ry6 from mice does not compromise viability. Our study thus nominates P2RY6 as a precision immunotherapy target for patients with high tumor-intrinsic P2RY6 expression. [Display omitted] • Aberrant P2RY6 expression is common in human cancers • Tumor-intrinsic P2RY6 promotes immune evasion • P2RY6 enhances cyclooxygenase expression to promote PGE 2 production Despite the efficacy of anti-PD-1 immunotherapy, many patients remain unresponsive, and predictive biomarkers are needed. Xu et al. identify P2RY6 as a key driver of immune evasion in cancers, promoting an immunosuppressive tumor microenvironment and resistance to immunotherapy, thus nominating P2RY6 as a precision immunotherapy target. [ABSTRACT FROM AUTHOR]

New evidence-based fasting guidelines have been published in recent years. However, while water and solid food fasting times before anesthesia are recommended to be 2 and 6 hours, respectively, these times are often longer in clinical practice. This study aimed to investigate the awareness and implementation of the fasting guideline recommendations among nurses and anesthesiologists, as well as evaluate the actual fasting durations in patients in a tertiary hospital. A cross-sectional study was used. Questionnaires were designed to collect the knowledge of fasting time among registered anesthesiologists and nurses. Data on the instructed and actual fasting durations among patients scheduled for elective surgery were evaluated. Approximately half of the nurses indicated that solid food fasting durations were shorter than 6 hours or longer than 8 hours, and two-thirds indicated that clear fluid fasting durations were shorter than 2 hours or longer than 4 hours. However, in clinical practice, nurse-instructed fasting durations were longer than what they knew was optimal. The anesthesiologists also prescribed longer fasting durations than the minimum fasting duration recommended. The actual fasting durations of the patients were significantly longer than the nurse-instructed fasting durations for solid food (13.41 ± 2.64 vs 9.87 ± 2.20 hours, P <.001) and clear fluids (10.27 ± 3.67 vs 8.98 ± 2.90 hours, P <.001). The nurse-instructed durations were significantly longer than the anesthesiologist-instructed durations according to the statements of patients (9.87 ± 2.20 vs 9.00 ± 2.00 hours for solid food, P <.001; 8.98 ± 2.90 vs 6.15 ± 3.25 hours for clear fluids, P <.001). Excessive fasting durations were observed among patients. Anesthesiologists and nurses must work together to ensure that updated fasting instructions are implemented in routine clinical practice. [ABSTRACT FROM AUTHOR]

• We recruited 15,830 participants aged 6–17 years across seven provinces in China. • Age- and sex-specific percentile curves were derived for serum lipids. • Levels of TC, nonHDL-C, LDL-C, HDL-C, and TG varied with age in both sexes. • Findings may provide evidence for screening of dyslipidemia in China. Current reference values for pediatric dyslipidemia used in China were not developed based on local population studies and did not consider age and sex differences. In this study, we aimed to determine suitable reference values for total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), and non-high-density lipoprotein cholesterol (nonHDL-C) for Chinese children and adolescents using a national multicenter school-based study. A total of 15,830 students aged 6–17 years were recruited from seven provinces of China. Age- and sex-specific percentile values for each lipid indicator were derived based on levels measured in the fasting state, and percentile curves of each indicator were plotted using the LMS method. Serum lipid levels varied considerably with age in both sexes. Among boys, the cut-off value for high TC, nonHDL-C, LDL-C, and TG, based on the value of the 95th percentiles, ranged from 4.58 to 5.39, 3.34 to 3.99, 2.69 to 3.31, and 1.22 to 1.83 mmol/L, respectively; among girls, the cut-off value for high TC, nonHDL-C, LDL-C, and TC ranged from 5.01 to 5.39, 3.66 to 3.97, 2.97 to 3.32, and 1.41 to 1.93 mmol/L, respectively. The cut-point for low HDL-C ranged from 0.84 to 1.08 mmol/L in boys and from 0.89 to 1.04 mmol/L in girls. These findings may help to determine age- and sex-specific reference values for serum lipids among Chinese children and adolescents and provide valuable guidance for screening of dyslipidemia. [ABSTRACT FROM AUTHOR]

According to ancient literature, Prunella vulgaris L. (P vulgaris) alleviates mastitis and has been used in China for many years; however, there are no relevant reports that confirm this or the mechanism of its efficacy. To explore the anti-acute mastitis effect and potential mechanism of P vulgaris extract. First, the active ingredients and targets of P vulgaris against mastitis were predicted using network pharmacology. Next, the relevant active ingredients were enriched using macroporous resins and verified using UV and UPLC-Q-TOF-MS/MS. Lastly, a mouse model of acute mastitis was established by injecting lipopolysaccharides into the mammary gland and administering P vulgaris extract by oral gavage. The pathological changes in mammary tissue were observed by HE staining. Serum and tissue inflammatory factors were measured by ELISA method. MPO activity in mammary tissue was measured using colorimetry and MPO expression was detected by immunohistochemistry. The expression of tight junction proteins (ZO-1, claudin-3, and occludin) in mammary tissue was detected by immunofluorescence and Western blot. iNOS and COX-2 in mammary tissue were detected by Western blot. MAPK pathway and NF-κB pathway related proteins were also detected by Western blot. Network pharmacology predicted that phenolic acids and flavonoids in P vulgaris had anti-mastitis effects. The contents of total flavonoids and total phenolic acids in P vulgaris extract were 64.5% and 29.4%, respectively. UPLC-Q-TOF-MS/MS confirmed that P vulgaris extract contained phenolic acids and flavonoids. The results of animal experiments showed that P vulgaris extract reduced lipopolysaccharide-induced inflammatory edema, inflammatory cell infiltration, and interstitial congestion of mammary tissue. It also reduced the levels of serum and tissue inflammatory factors TNF-α, IL-6, and IL-1β, and inhibited the activation of MPO. Furthermore, it downregulated the expression of MAPK and NF-κB pathway-related proteins. The expressions of ZO-1, occludin, and claudin-3 in mammary gland tissues were upregulated. P vulgaris extract can maintain the integrity of mammary connective tissue and reduce its inflammatory response to prevent acute mastitis. Its mechanism probably involves regulating NF-κB and MAPK pathways. [Display omitted] • Phenolic acids and flavonoids in P vulgaris may be effective ingredients of Prunella vulgaris L for anti-mastitis. • Experimental evidence supports P vulgaris as a potential remedy for acute mastitis. • UPLC-Q-TOF-MS/MS confirms phenolic acids and flavonoids in P vulgaris extract. • P vulgaris extract can improve the inflammatory reaction in the mammary gland tissue. [ABSTRACT FROM AUTHOR]

Emerging research into metabolic dysfunction-associated steatotic liver disease (MASLD) up until January 2024 has highlighted the critical role of cuproptosis, a unique cell death mechanism triggered by copper overload, in the disease's development. This connection offers new insights into MASLD's complex pathogenesis, pointing to copper accumulation as a key factor that disrupts lipid metabolism and insulin sensitivity. The identification of cuproptosis as a significant contributor to MASLD underscores the potential for targeting copper-mediated pathways for novel therapeutic approaches. This promising avenue suggests that managing copper levels could mitigate MASLD progression, offering a fresh perspective on treatment strategies. Further investigations into how cuproptosis influences MASLD are essential for unraveling the detailed mechanisms at play and for identifying effective interventions. The focus on copper's role in liver health opens up the possibility of developing targeted therapies that address the underlying causes of MASLD, moving beyond symptomatic treatment to tackle the root of the problem. The exploration of cuproptosis in the context of MASLD exemplifies the importance of understanding metal homeostasis in metabolic diseases and represents a significant step forward in the quest for more effective treatments. This research direction lights path for innovative MASLD management and reversal. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Considering that the quality control indicators in Chinese medicine (CM) are disconnected from safety and effectiveness, Prof. Chang-xiao Liu et al. has proposed a concept regarding the quality marker (Q-marker) of CM to promote the healthy development of the CM industry and improve the CM quality control method.Purpose: In this study, we proposed a strategy to discover and verify the toxicity Q-marker of CM based on network toxicology.Methods: First, traditional biochemical pathology indicators and sensitive biomarkers were used to predict the toxicity of CM. Next, the chemical composition of toxic CMs and their metabolites were rapidly identified by multidimensional detection techniques. Subsequently, the interaction network between "toxicity - toxic chemical composition - toxic target - effect pathway" was built through network toxicology, and the potential toxicity Q-marker of CM was initially screened. Finally, the chemical properties of toxicity Q-markers were verified by traceability and testability.Results: Based on the predicted results of network toxicology, the toxic compounds of CM were preliminarily identified, and the toxic mechanism was comprehensively interpreted. In the context of definite biological properties and chemical properties, the toxicity Q-marker was finally confirmed.Conclusion: This extensive review provides a study method for the toxicity Q-marker of CM, which helps to systemically and thoroughly reveal the internal toxicity mechanism of CM. The in-depth study of the toxicity Q-marker provides the material basis and technical support for the safety evaluation of CM. [ABSTRACT FROM AUTHOR]

Aconiti Lateralis Radix Praeparata- Fritillariae Thunbergii bulbus , namely Fuzi- Beimu in Chinese, is a classic herb pair whose combined administration was prohibited according to the rule of “Eighteen antagonisms”. However, incompatibility of Fuzi and Beimu has become controversial because of the application supported by many recorded ancient prescriptions and increasing modern researches and clinical practice. The present study aimed to investigate the pharmacokinetic differences of multiple alkaloids from Fuzi- Beimu and the single herb aqueous extracts following oral delivery in rats. Twelve alkaloids including aconitine, mesaconitine, hypaconitine, benzoylaconitine, benzoylmesaconitine, benzoylhypacoitine, neoline, fuziline, talatisamine, chasmanine, peimine and peimisine in rat plasma were simultaneously quantitated by using sensitive ultra-high performance liquid chromatography- tandem mass spectrometry (UHPLC–MS/MS), with the method developed and fully validated. Plasma concentrations of the twelve alkaloids after administration were determined and pharmacokinetic parameters were compared. Significant differences were observed for all alkaloids except aconitine, mesaconitine and benzoylaconitine for Fuzi- Beimu group in comparison with the single herb group. AUC 0-t and T 1/2 of hypaconitine were increased significantly. AUC 0-t and C max were increased and T max decreased significantly for benzoylmesaconitine and benzoylhypacoitine. Fuziline showed significantly increased AUC 0-t , C max and T max . T 1/2 of neoline was notably increased. T 1/2 and T max were significantly elevated for talatisamine while C max decreased. T max of chasmanine was significantly increased and C max decreased. Extremely significant increase of T max was found for peimisine, and significant increase of T 1/2 for peimine. Results revealed that combined use of Fuzi and Beimu significantly influenced the system exposure and pharmacokinetic behaviors of multiple alkaloids from both herbs, indicating herb- herb interaction between Fuzi and Beimu. [ABSTRACT FROM AUTHOR]

Ebracteolatain A (EA) is an acetyl-phloroglucinol compound extracted from Euphorbiae Ebracteolatae Radix, which has been shown to have antitumor activity. Current research addressed the antitumor activity of EA in breast cancer and further clarified its mechanism. Based on the pharmacodynamic evaluation in breast cancer cells and animal models, the antitumor effects of EA will be validated in vitro and in vivo. Breast cancer cells were processed with increasing concentrations of EA. CCK-8 and colony formation assays were employed to examine the effects of EA on proliferation and survival. Flow cytometry detected the blocking function of EA on the cell cycle. The specific mechanism of EA in breast cancer was studied by transfection experiments and Western Blot analysis. Finally, a nude mice xenograft tumor model was constructed to assess the therapeutic and potential mechanism of EA. We proved that EA caused a dose-dependent inhibition on MCF-7 and MDA-MB-415 cells with IC 50 of 6.164 and 6.623 μmol/l, respectively. While EA reduced cell proliferation and clone formation, and markedly arrested cells in the G 0 /G 1 phase. In vivo , EA remarkably suppressed the tumor weight and volume in xenograft nude mice. Besides, PKD1 reversed the inhibition of EA on breast cancer cell proliferation, clone formation, and cycle arrest, and restored tumor growth in xenograft nude mice. Western Blot confirmed that EA regulates breast cancer by suppressing PKD1 in MEK/ERK and PI3K/AKT signaling pathways. Herein, we first confirmed EA exerts anti-proliferation by inhibiting PKD1 in MEK/ERK and PI3K/AKT signaling pathways, indicating that EA is a prodigious breast cancer drug candidate. [Display omitted] [ABSTRACT FROM AUTHOR]

Thermostability has been considered as a requirement in the starch processing industry to maintain high catalytic activity of pullulanase under high temperatures. Four data driven rational design methods (B-FITTER, proline theory, PoPMuSiC-2.1, and sequence consensus approach) were adopted to identify the key residue potential links with thermostability, and 39 residues of Bacillus acidopullulyticus pullulanase were chosen as mutagenesis targets. Single mutagenesis followed by combined mutagenesis resulted in the best mutant E518I-S662R-Q706P, which exhibited an 11-fold half-life improvement at 60 °C and a 9.5 °C increase in T m . The optimum temperature of the mutant increased from 60 to 65 °C. Fluorescence spectroscopy results demonstrated that the tertiary structure of the mutant enzyme was more compact than that of the wild-type (WT) enzyme. Structural change analysis revealed that the increase in thermostability was most probably caused by a combination of lower stability free-energy and higher hydrophobicity of E518I, more hydrogen bonds of S662R, and higher rigidity of Q706P compared with the WT. The findings demonstrated the effectiveness of combined data-driven rational design approaches in engineering an industrial enzyme to improve thermostability. [ABSTRACT FROM AUTHOR]

• A new Au@Cu-HCF nanozyme was developed and characterized. • A novel Au@Cu-HCF-based colorimetric strategy was developed for TAC in foods. • A smartphone-based sensor was constructed based on the colorimetric strategy. Gold doped copper hexacyanoferrate (Au@Cu-HCF) nanozyme-based colorimetric sensing strategies were exploited to measure total antioxidant capacity (TAC) of some plant-derived food samples. The new developed Au@Cu-HCF nanozyme replaces natural enzymes to catalyze a redox reaction, and antioxidants can compete with substrates in the interaction with OH , leading to an antioxidant concentration-dependent color change. Depending on the Au@Cu-HCF-based ABTS colorimetric strategy, a smartphone-based sensor was devised using smartphone's camera as a "smart detector". The proposed sensor was successfully utilized to measure the TAC of lotus root (4.61 mM), citrus juice (6.35 mM), and lemon beverage (1.00 mM) with standard deviations of 0.16 mM, 0.16 mM, and 0.06 mM, respectively. These results all agree well with the commercial kit (4.55 mM for lotus root, 6.27 mM for citrus juice and 1.11 mM for lemon beverage), indicating this sensor has good practical applications in the TAC measurement of food samples. [ABSTRACT FROM AUTHOR]

Mitochondria are known as the powerhouse of the cell. Dysfunction of mitochondria homeostasis induces the mitochondrial unfolded protein response (UPRmt), altering cellular metabolism. How cells sense the UPRmt to rewire metabolism is largely unknown. Here, we show that inactivation of either the citric/tricarboxylic acid (TCA) cycle enzymes aco-2 or idha-1, which encode aconitase and isocitrate dehydrogenase respectively, leads to citrate accumulation. In Caenorhabditis elegans , both in vitro and in vivo , citrate accumulation consequently triggers the UPRmt and also promotes lipid accumulation. The transcription factor DVE-1 binds to the promoter of the nuclear hormone receptor nhr-80 to transactivate its expression. NHR-80 then upregulates lipogenesis and lipid accumulation, shifting excess citrate for use in lipogenesis and for storage as triacylglycerol in lipid droplets. Inactivation of DVE-1 or NHR-80 fully abolishes the citrate-induced lipid accumulation. Therefore, our work uncovers a DVE-1-NHR-80-lipogenesis axis linking the transmission of the mitochondrial stress signal to lipid metabolism. [Display omitted] • Inactivation of the TCA cycle or dietary citrate elicits the UPRmt pathway • DVE-1 responds to citrate-induced UPRmt to regulate lipid metabolism • NHR-80 acts downstream of DVE-1 to transactivate lipogenesis under citrate stress How cells sense the mitochondrial unfolded protein response (UPRmt) to rewire metabolism is largely unknown. Yang et al. show a metabolic rerouting mechanism orchestrated by NHR-80 occurring downstream of the UPRmt component DVE-1. This work uncovers a DVE-1-NHR-80-lipogenesis axis linking the transmission of the mitochondrial stress signal to lipid metabolism [ABSTRACT FROM AUTHOR]

Schistosomiasis, caused by infection with organisms of the Schistoma genus, is a parasitic and infectious disease that poses a significant risk to human health. Schistosomiasis has been a widespread issue in China for at least 2000 years. Traditional Chinese medicine (TCM) has a rich history of treating this disease, and the significant theoretical and practical knowledge attained therein may be useful in modern practice. To comprehensively review TCM for the treatment of schistosomiasis, summarize the molecular basis, mechanism of action, active ingredients and formulas of TCM, and clarify the value of TCM for expanding drug options for the clinical treatment of schistosomiasis. In PubMed, Web of Science, ScienceDirect, Google Scholar and CNKI databases, "Schistosomiasis", " Schistosoma mansoni ", " Schistosoma japonicum ", "Liver fibrosis" and "Granuloma" were used as the key words. Information related to in vivo animal studies and clinical studies of TCM for the treatment of schistosomiasis in the past 25 years was retrieved, and the inclusion criteria focused on medicinal plants that had a history of use in China. In this study, we collected and organized a large amount of literature on the treatment of schistosomiasis by TCM. TCM exerts therapeutic effects through antischistosomal and immunomodulatory effects, suppresses HSC activation and proliferation, reduces ECM deposition, and inhibits oxidative stress and other activities. The treatment of schistosomiasis by TCM has a unique advantage, especially for the treatment of schistosomal liver fibrosis, and the treatment of schistosomiasis with TCM in combination with praziquantel is superior to monotherapy. Schistosomiasis remains a global public health problem, and TCM has made significant progress in the prevention and treatment of schistosomiasis and is a potential source of drugs for the treatment of schistosomiasis. However, research on drug screening and the mechanism of action of TCM for the treatment of schistosomiasis is lacking, and further studies and research are needed. [Display omitted] • Research progress of Chinese single herbs, active ingredients and formulas against schistosomiasis was comprehensively reviewed for the first time. • Summarized the potential mechanisms of TCM against schistosomiasis. • Summarized the clinical researchs of TCM against schistosomiasis, and discussed the advantages of combining TCM with PZQ, specially for schistosomiasis liver fibrosis. • Discussed the limitations and shortcomings of TCM against schistosomiasis, providing guidance for future research. [ABSTRACT FROM AUTHOR]

• We systematically investigated the history and potential impact of land consolidation in China. • The mechanism of land consolidation promoting rural revitalization was analyzed. • Land consolidation can provide a platform and lever and injects vitality for revitalizing the countryside. • Land consolidation is moving towards multi-objective and multi-functional transformation. • Land consolidation shows its social, economic and ecological benefits, but its potential risks cannot be ignored. Land consolidation has multi-functionality. Most of the existing researches focus on the supplementary function of cultivated land, but lack of systematic research on its function of promoting the sustainable development and revitalization of rural areas. In the context of the current global rural decline, land consolidation has been endowed with the connotation of promoting rural revitalization and regional sustainable development. This study systematically reviewed the evolution history of land consolidation in China, and then explored the current status, characteristics and potential impact of land consolidation as well as the driving mechanism of land consolidation promoting rural revitalization, and finally explained the feasible way to revitalize countryside by land consolidation in a typical case. Results showed that China's land consolidation has played an irreplaceable role in stabilizing the dynamic balance of arable land and ensuring food security. It has made or is moving towards supporting the development of modern agriculture, poverty alleviation and rural revitalization as well as regional sustainable development. Land consolidation is gradually favored in promoting rural development and revitalization because of its social, economic and ecological benefits, and it can provide a platform and inject new vitality for rural revitalization by solving the difficulties of lack of fund, land, technology, talent and industry. Comprehensive land consolidation helps to promote the overall revitalization of rural industry, ecology, organization, culture and talent. However, it also needs to be alert to the eco-environmental risks and negative effects brought by land consolidation projects. The problem-solving oriented land consolidation is needed in the process of promoting rural revitalization and regional sustainable development. The internal logic of rural decline at different development stages varies across countries, and the strategies to promote rural revitalization through land consolidation also need to be adjusted in time. [ABSTRACT FROM AUTHOR]

• This assay bridges the gap between molecular diagnostic assays and antimicrobial resistance (AMR) detection in Neisseria gonorrhoeae (N. gonorrhoeae). • The high-resolution melting assay of N. gonorrhoeae AMR (HRM-NG-AMR) assay showed promising diagnostic performance for detecting N. gonorrhoeae infection and predicting AMR. • 40 genotypic FC428-related strains with the penA -60.001 allele were accurately identified. • This assay can be used to enhance AMR surveillance and inform treatment. Antimicrobial resistance (AMR) in Neisseria gonorrhoeae (N. gonorrhoeae) is an urgent threat to public health, with the emergence of highly resistant strains such as the FC428 clone. This study aimed to evaluate the high-resolution melting assay of N. gonorrhoeae AMR (HRM-NG-AMR) for diagnosing N. gonorrhoeae infection and detecting extended-spectrum cephalosporins and azithromycin resistance. A multicentre collection of 1488 samples, including 770 isolates and 718 urogenital swabs, was used to evaluate the performance of the HRM-NG-AMR assay. The presence of N. gonorrhoeae was confirmed by culture. Minimum inhibitory concentrations of antibiotics against the tested isolates were determined using the agar dilution method. Regarding N. gonorrhoeae identification, HRM-NG-AMR had a sensitivity of 95.15% (95% CI 91.65–97.28) and a specificity of 96.44% (95% CI 94.17–97.89) using culture as standard. Regarding AMR detection, the specificity ranged from 96.29% (95% CI 94.57–97.50) for cefixime to 99.52% (95% CI 98.68–99.85) for azithromycin. Additionally, the sensitivity ranged from 31.34% (95% CI 20.87–43.97) for azithromycin to 79.10% (95% CI 63.52–89.42) for ceftriaxone. It was determined that 664 of 672 (98.81%) and 615 of 672 (91.52%) N. gonorrhoeae isolates were susceptible to ceftriaxone and cefixime, respectively, by detecting non-mosaic penA. Lastly, 40 genotypic FC428-related strains with the penA -60.001 allele were accurately identified. The HRM-NG-AMR assay showed promising diagnostic performance for detecting N. gonorrhoeae infection and predicting AMR. This study aimed to evaluate the application of this assay in the clinical setting to enhance AMR surveillance and treatment intervention. [Display omitted] [ABSTRACT FROM AUTHOR]

Fuke Qianjin Capsule (FKC), a traditional Chinese medicine commonly employed for treating endometritis, lacks reported treatment mechanisms. The aim of the present study was to explore the role and mechanism of FKC in lipopolysaccharide (LPS)-induced endometritis. The main active ingredients of FKC were identified via high-performance liquid chromatography (HPLC) in conjunction with standard substances. Prior to endometritis induction, Sprague Dawley female rats received FKC for 7 days. The endometritis model was established through an intrauterine injection of 1 mg/kg LPS. Concurrently, an LPS-induced RAW264.7 cell inflammation model was utilized, in which the cells were treated with serum containing Fuke Qianjin Capsule. Pathological alterations in the endometrium were assessed via H&E staining and transmission electron microscopy (TEM). The contents of MPO in uterine tissues, and NO release in cells, along with the secretion of IL-18, IL-1β, IL-6, and TNF-α in both tissues and cells, were determined via assay kits. The mRNA levels of Nlrp3 , Caspase-1 , Gsdmd , and Il-1β in uterine tissues and cells were analyzed via qPCR. The protein levels of TLR4, p65, p-P65, NLRP3, Caspase-1, GSDMD, and IL-1β in these samples were evaluated through Western blot analysis. Immunofluorescence was used to assess the protein levels of p-P65 and NLRP3 in uterine tissues and cells. Five primary active components of FKC were identified. Treatment with FKC in vivo mitigated endometrial pathological damage and significantly decreased the levels of MPO, IL-18, IL-1β, IL-6, and TNF-α, as well as the levels of Nlrp3 , Caspase-1 , Gsdmd , and Il-1β mRNA in tissue samples. Treatment with FKC inhibited the expression of TLR4, p-P65, NLRP3, Caspase-1, GSDMD, and IL-1β, as well as reduced NLRP3 protein fluorescence intensity, and inhibited P65 phosphorylation. In vitro findings demonstrated that FKC-containing serum reduced IL-18, IL-1β, IL-6, and TNF-α levels, as well as reduced Nlrp3 , Caspase-1 , Gsdmd , and Il-1β mRNA levels. In addition, FKC-containing serum inhibited the protein expression of TLR4, p-P65, NLRP3, Caspase-1, GSDMD, and IL-1β. FKC-containing serum also reduced NLRP3 protein fluorescence intensity and suppressed P65 phosphorylation. FKC reverses the LPS induced NLRP3 inflammasome activation, and mitigates inflammation and pyroptosis through the modulation of the TLR4/NF-κB/NLRP3 pathway, thereby alleviating endometritis. [Display omitted] • The pharmacological effects of Fuke Qianjin capsules on endometritis were verified from both in vivo and in vitro perspectives. • The mechanism of action of Fuke Qianjin capsules against endometritis has been clarified: regulating inflammation and pyroptosis mediated by the TLR4/NF-κB/NLRP3 signaling pathway. • Expand the application of Fuke Qianjin capsules in gynecological diseases. [ABSTRACT FROM AUTHOR]

Postoperative pulmonary complications (PPCs), the predominant complications following lung surgery, are closely associated with intraoperative fluid therapy. This study investigates whether continuous low-dose norepinephrine infusion combined with goal-directed fluid therapy (GDFT) reduced the risk of PPCs after lung surgery relative to either GDFT alone or standard fluid treatment. A prospective, randomized controlled trial. The First Affiliated Hospital of Anhui Medical University, Anhui, China. The study included 184 patients undergoing elective thoracoscopic lung resection surgery. Patients were randomized into three groups based on different fluid treatment regimens: Group C received standard fluid treatment, Group G received GDFT, and Group N received continuous low-dose norepinephrine infusion combined with GDFT. The primary outcome was the incidence of PPCs, including respiratory infection, atelectasis, pneumothorax, pleural empyema, respiratory failure, pulmonary embolism and bronchopleural fistula, during the postoperative hospital stay. Secondary outcomes were hemodynamic variables and arterial blood gases. Additional recorded parameters included other postoperative complications such as bleeding, postoperative re-intubation, re-hospitalization within 30 days, and the length of hospital stay. Group N showed a significantly lower PPCs incidence during hospitalization compared to Group C (11.5 % vs 27.9 %; odds ratio, 2.98; 95 % confidence interval, 1.17–8.31; P = 0.023). No significant difference in PPCs was found between Group N and Group G (11.5 % vs 14.5 %; odds ratio, 1.31; 95 % confidence interval, 0.46–3.91; P = 0.616). Additionally, there were no significant differences among the three groups in the components of PPCs. Group N showed higher mean arterial pressure and stroke volume index intraoperatively compared to Group C. Continuous low-dose norepinephrine infusion combined with GDFT reduced PPCs incidence in elective lung surgery patients compared with standard fluid management, but showed no difference compared to GDFT alone. ChiCTR2200064081. [Display omitted] • Postoperative pulmonary complications are related with fluid therapy. • Combined low-dose norepinephrine and goal-directed fluid therapy in trial. • Significantly fewer pulmonary complications in treatment group. • Supports new protocols for fluid management in lung surgeries. [ABSTRACT FROM AUTHOR]

[Display omitted] Arbutin, a typical optical isomer, has garnered widespread acclaim in the whitening cosmetics for its favorable efficacy and safety. However, the molecular mechanisms underlying α-arbutin and β-arbutin permeating across the skin have not elucidated clearly yet. Herein we aimed to unveil how α-arbutin and β-arbutin interacted with keratin or SC lipids, further demonstrating their relationship with their drug permeability. We found that α-arbutin displayed significantly higher drug accumulation into the porcine skin than β-arbutin within 24 h through in vitro permeation test. Moreover, α-arbutin predominantly induced the alternations of secondary structure of amide II during the drug permeation, which was favorable for α-arbutin permeation. On the contrary, β-arbutin exhibited an observable effect on the stretching vibration of SC lipids, possessing a significantly stronger mixing energy, binding energy and compatibility with ceramide (Cer) than that of α-arbutin, which ultimately restricted its permeation. Interestingly, free fatty acids and ceramides of the SC lipids specifically utilized its oxygen atom of carboxyl group to dock the arbutin molecules, enhancing their affinity with β-arbutin, as confirmed by molecular simulation and 13Carbon Nuclear Magnetic Resonance. Nevertheless, a favorable compatibility between α-arbutin and keratin was observed. It was emphasized that the distinct spatial configuration and opposite optical rotation of arbutin was the leading factor impacting the intermolecular force between arbutin and the SC, and resulted in a diverse drug permeation. In cellular and in vivo skin pharmacokinetic studies, α-arbutin also possessed a higher cellular uptake and topical bioavailability than β-arbutin. This study revealed the transdermal permeation mechanisms of optical isomer arbutin at the molecular levels, providing methodological reference for the investigations of permeation behaviors of other isomers with similar spatial configuration. [ABSTRACT FROM AUTHOR]

Steroid-based drugs have been developed as the second largest medical category in pharmaceutics. The well-established route of steroid industry includes two steps: the conversion of natural products with a steroid framework to steroid-based drug intermediates and the synthesis of varied steroid-based drugs from steroid-based drug intermediates. The biosynthesis of steroid-based drug intermediates from phytosterols by Mycolicibacterium cell factories bypasses the potential undersupply of diosgenin in the traditional steroid chemical industry. Moreover, the biosynthesis route shows advantages on multiple steroid-based drug intermediate products, more ecofriendly processes, and consecutive reactions carried out in one operation step and in one pot. Androsta-4-ene-3,17-dione (AD), androsta-1,4-diene-3,17-dione (ADD) and 9-hydroxyandrostra-4-ene-3,17-dione (9-OH-AD) are the representative steroid-based drug intermediates synthesized by mycolicibacteria. Other steroid metabolites of mycolicibacteria, like 4-androstene-17β-ol-3-one (TS), 22-hydroxy-23,24-bisnorchol-4-ene-3-one (4-HBC), 22-hydroxy-23,24-bisnorchol-1,4-diene-3-one (1,4-HBC), 9,22-dihydroxy-23,24-bisnorchol-4-ene-3-one (9-OH-HBC), 3aα- H -4α-(3′-propionic acid)-7aβ-methylhexahydro-1,5-indanedione (HIP) and 3aα- H -4α-(3′-propionic acid)-5α-hydroxy-7aβ-methylhexahydro-1-indanone-δ-lactone (HIL), also show values as steroid-based drug intermediates. To improve the bio-production efficiency of the steroid-based drug intermediates, mycolicibacterial strains and biotransformation processes have been continuously studied in the past decades. Many mycolicibacteria that accumulate steroid drug intermediates have been isolated, and subsequently optimized by conventional mutagenesis and genetic engineering. Especially, with the clarification of the mycolicibacterial steroid metabolic pathway and the developments on gene editing technologies, rational design is becoming an important measure for the construction and optimization of engineered mycolicibacteria strains that produce steroid-based drug intermediates. Hence, by reviewing researches in the past two decades, this article updates the overall process of steroid metabolism in mycolicibacteria and provides comprehensive schemes for the rational construction of mycolicibacterial strains that accumulate steroid-based drug intermediates. In addition, the special strategies for the bioconversion of highly hydrophobic steroid in aqueous media are discussed as well. [ABSTRACT FROM AUTHOR]

Prunella vulgaris L. (P. vulgaris , Labiatae) is a perennial medicinal and edible plant widely used in China, Korea, Japan and Europe. The reddish brown spica of P. vulgaris (Prunellae Spica), which is collected in summer, has been commonly used in traditional medicine and food industry, while it is also used with whole grass in Europe and Taiwan. To clarify the regulatory pathways and mechanism of quality formation in P. vulgaris , targeted metabolomic, transcriptomic, and proteomic analyses of Prunellae Spica samples from five consecutive developmental stages were carried out. The results showed that terpenoids were mainly synthesized in the maturity stage of Prunellae Spica, with the key enzymes and coding genes in downstream pathways being mainly expressed during ripening, while related enzymes in the upstream pathway showed the opposite pattern. Flavonoids mainly accumulated before ripening, with highly expressed pathway enzymes and coding genes. The accumulation of phenylpropanoids was relatively active throughout the development process. Rosmarinic acid (RA) and its synthetic intermediate products mainly accumulated via more active pathway enzymes and coding genes before ripening. The regulatory factors and metabolites related to RA synthesis were mainly enriched in phenylpropanoid biosynthesis, plant hormone signal transduction, plant pathogen interaction, oxidative phosphorylation, and endoplasmic reticulum protein processing pathways. [Display omitted] [ABSTRACT FROM AUTHOR]