Discrimination between raw and ginger juice processed Fructus Gardeniae based on UHPLC-Q-TOF-MS and Heracles NEO ultra-fast gas phase electronic nose.

INTRODUCTION: Fructus Gardeniae (ZZ), a traditional Chinese herb, has been used in treating patients with jaundice, inflammation, etc. When mixed with ginger juice and stir-baked, ginger juice-processed Fructus Gardeniae (JZZ) is produced, and the chemical compositions in ZZ would be changed by adding the ginger juice. OBJECTIVE: To illuminate the differential components between ZZ and JZZ. METHODS: HPLC, UHPLC-Q-TOF-MS, and Heracles NEO ultra-fast gas phase electronic nose were applied to identify the differential components between ZZ and JZZ. RESULTS: HPLC fingerprints of ZZ and JZZ were established, and 24 common peaks were found. The content determination results showed that the contents of shanzhiside, geniposidic acid, genipin-1-ß-D-gentiobioside and geniposide increased, while the contents of crocin I and crocin II decreased in JZZ. By UHPLC-Q-TOF-MS, twenty-six possible common components were inferred, among which 11 components were different. In further investigation, eight components were identified as the possible distinctive non-volatile compounds between ZZ and JZZ. By Heracles NEO ultra-fast gas phase electronic nose, four substances were inferred as the possible distinctive volatile compounds in JZZ. CONCLUSION: Shanzhiside, caffeic acid, genipin-1-ß-D-gentiobioside, geniposide, rutin, crocin I, crocin II, and 4-Sinapoyl-5-caffeoylquinic acid were identified as the possible differential non-volatile components between ZZ and JZZ. Aniline, 3-methyl-3-sulfanylbutanol-1-ol, E-3-octen-2-one, and decyl propaonate were inferred as the possible distinctive volatile compounds in JZZ. This experiment explored a simple approach with objective and stable results, which would provide new ideas for studying decoction pieces with similar morphological appearance, especially those with different odors.

Integrated Transcriptomic and Metabolomic Analysis Reveals the Molecular Regulatory Mechanism of Flavonoid Biosynthesis in Maize Roots under Lead Stress.

Flavonoids are secondary metabolites that play important roles in the resistance of plants to abiotic stress. Despite the widely reported adverse effects of lead (Pb) contamination on maize, the effects of Pb on the biosynthetic processes of flavonoids in maize roots are still unknown. In the present work, we employed a combination of multi-omics and conventional assay methods to investigate the effects of two concentrations of Pb (40 and 250 mg/kg) on flavonoid biosynthesis in maize roots and the associated molecular regulatory mechanisms. Analysis using conventional assays revealed that 40 and 250 mg/kg Pb exposure increased the lead content of maize root to 0.67 ± 0.18 mg/kg and 3.09 ± 0.02 mg/kg, respectively, but they did not result in significant changes in maize root length. The multi-omics results suggested that exposure to 40 mg/kg of Pb caused differential expression of 33 genes and 34 metabolites related to flavonoids in the maize root system, while 250 mg/kg of Pb caused differential expression of 34 genes and 31 metabolites. Not only did these differentially expressed genes and metabolites participate in transferase activity, anthocyanin-containing compound biosynthetic processes, metal ion binding, hydroxyl group binding, cinnamoyl transferase activity, hydroxycinnamoyl transferase activity, and flavanone 4-reductase activity but they were also significantly enriched in the flavonoid, isoflavonoid, flavone, and flavonol biosynthesis pathways. These results show that Pb is involved in the regulation of maize root growth by interfering with the biosynthesis of flavonoids in the maize root system. The results of this study will enable the elucidation of the mechanisms of the effects of lead on maize root systems.

Opposite response of constructed wetland performance in nitrogen and phosphorus removal to short and long terms of operation.

Constructed wetlands (CWs) have been widely used for treating polluted water since the 1950s, with applications in over 50 countries worldwide. Most studies investigating the pollutant removal efficiency of these wetlands have focused on differences among wetland designs, operation strategies, and environmental conditions. However, there still remains a gap in understanding the variation in wetland pollutant removal efficiency over different time scales. Therefore, the main aim of the study is to address this gap by conducting a global meta-analysis to estimate the variation in nitrogen (N) and phosphorus (P) removal by wetland in short- and long-term pollutant treatment. The findings of this study indicated that the total efficiencies of N and P removal increased during short-term wetland operation but decreased during long-term operation. However, for surface flow CWs specifically, the efficiencies of N and P removal increased during short-term operation and remained stable during long-term operation. Moreover, the study discovered that wetland N removal efficiency was influenced by seasons, with an increase in spring and summer and a decrease in autumn and winter. Conversely, there was no significant seasonal effect on P removal efficiency. Additionally, high hydraulic load impaired wetland N and P removal efficiency during long-term operation. This study offers a critical review of the role of wetlands in wastewater treatment and provides valuable reference data for the design and selection of CWs types during wastewater treatment in the aspect of sustainability.

Soil microbial communities' contributions to soil ecosystem multifunctionality in the natural restoration of abandoned metal mines.

On a global scale, the restoration of metal mine ecosystem functions is urgently required, and soil microorganisms play an important role in this process. Conventional studies frequently focused on the relationship between individual functions and their drivers; however, ecosystem functions are multidimensional, and considering any given function in isolation ignores the trade-offs and interconnectedness between functions, which complicates obtaining a comprehensive understanding of ecosystem functions. To elucidate the relationships between soil microorganisms and the ecosystem multifunctionality (EMF) of metal mines, this study investigated natural restoration of metal mines, evaluated the EMF, and used high-throughput sequencing to explore the bacterial and fungal communities as well as their influence on EMF. Bacterial community diversity and composition were more sensitive to mine restoration than fungal community. Bacterial diversity exhibited redundancy in improving N-P-K-S multifunctionality; however, rare bacterial taxa including Dependentiae, Spirochaetes, and WPS-2 were important for metal multifunctionality. Although no clear relationship between fungal diversity and EMF was observed, the abundance of Glomeromycota had a significant effect on the three EMF categories (N-P-K-S, carbon, and metal multifunctionality). Previous studies confirmed a pronounced positive association between microbial diversity and multifunctionality; however, the relationship between microbial diversity and multifunctionality differs among functions' categories. In contrast, the presence of critical microbial taxa exerted stronger effects on mine multifunctionality.

N-acetylgalactosaminyltransferase-4 protects against hepatic ischemia/reperfusion injury by blocking apoptosis signal-regulating kinase 1 N-terminal dimerization.

BACKGROUND AND AIMS: Ischemia-reperfusion (I/R) injury is an inevitable complication of liver transplantation (LT) and compromises its prognosis. Glycosyltransferases have been recognized as promising targets for disease therapy, but their roles remain open for study in hepatic I/R (HIR) injury. Here, we aim to demonstrate the exact function and molecular mechanism of a glycosyltransferase, N-acetylgalactosaminyltransferase-4 (GALNT4), in HIR injury. APPROACH AND RESULTS: By an RNA-sequencing data-based correlation analysis, we found a close correlation between GALNT4 expression and HIR-related molecular events in a murine model. mRNA and protein expression of GALNT4 were markedly up-regulated upon reperfusion surgery in both clinical samples from subjects who underwent LT and in a mouse model. We found that GALNT4 deficiency significantly exacerbated I/R-induced liver damage, inflammation, and cell death, whereas GALNT4 overexpression led to the opposite phenotypes. Our in-depth mechanistic exploration clarified that GALNT4 directly binds to apoptosis signal-regulating kinase 1 (ASK1) to inhibit its N-terminal dimerization and subsequent phosphorylation, leading to a robust inactivation of downstream c-Jun N-terminal kinase (JNK)/p38 and NF-κB signaling. Intriguingly, the inhibitory capacity of GALNT4 on ASK1 activation is independent of its glycosyltransferase activity. CONCLUSIONS: GALNT4 represents a promising therapeutic target for liver I/R injury and improves liver surgery prognosis by inactivating the ASK1-JNK/p38 signaling pathway.

Effects of Heavy Metals on Stomata in Plants: A Review.

Stomata are one of the important structures for plants to alleviate metal stress and improve plant resistance. Therefore, a study on the effects and mechanisms of heavy metal toxicity to stomata is indispensable in clarifying the adaptation mechanism of plants to heavy metals. With the rapid pace of industrialization and urbanization, heavy metal pollution has been an environmental issue of global concern. Stomata, a special physiological structure of plants, play an important role in maintaining plant physiological and ecological functions. Recent studies have shown that heavy metals can affect the structure and function of stomata, leading to changes in plant physiology and ecology. However, although the scientific community has accumulated some data on the effects of heavy metals on plant stomata, the systematic understanding of the effects of heavy metals on plant stomata remains limited. Therefore, in this review, we present the sources and migration pathways of heavy metals in plant stomata, analyze systematically the physiological and ecological responses of stomata on heavy metal exposure, and summarize the current mechanisms of heavy metal toxicity on stomata. Finally, the future research perspectives of the effects of heavy metals on plant stomata are identified. This paper can serve as a reference for the ecological assessment of heavy metals and the protection of plant resources.

Estimation of surface ozone concentration over Jiangsu province using a high-performance deep learning model.

Recently, the global background concentration of ozone (O3) has demonstrated a rising trend. Among various methods, groun-based monitoring of O3 concentrations is highly reliable for research analysis. To obtain information on the spatial characteristics of O3 concentrations, it is necessary that the ground monitoring sites be constructed in sufficient density. In recent years, many researchers have used machine learning models to estimate surface O3 concentrations, which cannot fully provide the spatial and temporal information contained in a sample dataset. To solve this problem, the current study utilized a deep learning model called the Residual connection Convolutional Long Short-Term Memory network (R-ConvLSTM) to estimate daily maximum 8-hr average (MDA8) O3 over Jiangsu province, China during 2020. In this research, the R-ConvLSTM model not only provides the spatiotemporal information of MDA8 O3, but also involves residual connection to avoid the problem of gradient explosion and gradient disappearance with the deepening of network layers. We utilized the TROPOMI total O3 column retrieved from Sentinel-5 Precursor, ERA5 reanalysis meteorological data, and other supplementary data to build a pre-trained dataset. The R-ConvLSTM model achieved an overall sample-base cross-validation (CV) R2 of 0.955 with root mean square error (RMSE) of 9.372 µg/m3. Model estimation also showed a city-based CV R2 of 0.896 with RMSE of 14.029 µg/m3, the highest MDA8 O3 in spring being 122.60 ± 31.60 µg/m3 and the lowest in winter being 69.93 ± 18.48 µg/m3.

[Processing Magnoliae Officinalis Cortex with ginger juice: process optimization based on AHP-CRITIC weighting method and composition changes after processing].

The weight coefficients of appearance traits, extract yield of standard decoction, and total content of honokiol and magnolol were determined by analytic hierarchy process(AHP), criteria importance though intercrieria correlation(CRITIC), and AHP-CRITIC weighting method, and the comprehensive scores were calculated. The effects of ginger juice dosage, moistening time, proces-sing temperature, and processing time on the quality of Magnoliae Officinalis Cortex(MOC) were investigated, and Box-Behnken design was employed to optimize the process parameters. To reveal the processing mechanism, MOC, ginger juice-processed Magnoliae Officinalis Cortex(GMOC), and water-processed Magnoliae Officinalis Cortex(WMOC) were compared. The results showed that the weight coefficients of the appearance traits, extract yield of standard decoction, and total content of honokiol and magnolol determined by AHP-CRITIC weighting method were 0.134, 0.287, and 0.579, respectively. The optimal processing parameters of GMOC were ginger juice dosage of 8%, moistening time of 120 min, and processing at 100 ℃ for 7 min. The content of syringoside and magnolflorine in MOC decreased after processing, and the content of honokiol and magnolol followed the trend of GMOC>MOC>WMOC, which suggested that the change in clinical efficacy of MOC after processing was associated with the changes of chemical composition. The optimized processing technology is stable and feasible and provides references for the modern production and processing of MOC.

Hepatocyte SH3RF2 Deficiency Is a Key Aggravator for NAFLD.

BACKGROUND AND AIMS: NAFLD has become the most common liver disease worldwide but lacks a well-established pharmacological therapy. Here, we aimed to investigate the role of an E3 ligase SH3 domain-containing ring finger 2 (SH3RF2) in NAFLD and to further explore the underlying mechanisms. METHODS AND RESULTS: In this study, we found that SH3RF2 was suppressed in the setting of NAFLD across mice, monkeys, and clinical individuals. Based on a genetic interruption model, we further demonstrated that hepatocyte SH3RF2 deficiency markedly deteriorates lipid accumulation in cultured hepatocytes and diet-induced NAFLD mice. Mechanistically, SH3RF2 directly binds to ATP citrate lyase, the primary enzyme promoting cytosolic acetyl-coenzyme A production, and promotes its K48-linked ubiquitination-dependent degradation. Consistently, acetyl-coenzyme A was significantly accumulated in Sh3rf2-knockout hepatocytes and livers compared with wild-type controls, leading to enhanced de novo lipogenesis, cholesterol production, and resultant lipid deposition. CONCLUSION: SH3RF2 depletion in hepatocytes is a critical aggravator for NAFLD progression and therefore represents a promising therapeutic target for related liver diseases.

Icariin Ameliorates Alzheimer's Disease Pathology by Alleviating Myelin Injury in 3 × Tg-AD Mice.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by excessive deposition of ß amyloid (Aß), hyperphosphorylation of tau protein, and neuronal cell death. Recent studies have shown that myelin cell damage, which leads to cognitive dysfunction, occurs before AD-related pathological changes. Here, we examine the effect of icariin (ICA), a prenylated flavonol glycoside, in improving cognitive function in AD model mice. ICA has been reported to exhibit cardiovascular protective functions and antiaging effects. In this study, we used 3 × Tg-AD mice as an AD model. The Morris water maze and Y maze tests were performed to assess the learning and memory of the mice. Immunofluorescence analysis of Aß1-42 deposition and myelin basic protein (MBP) expression in the mouse hippocampus was performed. Tau protein phosphorylation and MBP protein expression in the hippocampus were further analyzed by Western blotting. Myelin damage in the mouse optic nerve was evaluated by electron microscopy, and LFB staining was performed to assess myelin morphology in the mouse corpus callosum. MBP, Mpp5, and Egr2 transcript levels were quantified by qPCR. We observed that ICA treatment improved the learning and memory of 3 × Tg-AD mice and reduced Aß deposition and tau protein phosphorylation in the hippocampus. Moreover, this treatment protocol increased myelin-related gene expression and reduced myelin damage.

Factors influencing caring behaviour among registered nurses during the COVID-19 pandemic in China: A qualitative study using the COM-B framework.

AIM: The aim of this work is to explore the influencing factors of nurses' caring behaviour during the COVID-19 pandemic based on the Capability, Opportunity, Motivation as determinants of Behaviour (COM-B) theoretical framework. BACKGROUND: Nurse caring behaviour is vital to reduce and speed up the healing process of COVID-19 patients. It is important to understand the factors that influence caring behaviour among nurses during the COVID-19 pandemic. Research suggests that when it comes to understanding behaviour, using a theoretical framework is likely to be most effective, and the COM-B framework is a recommended approach. METHODS: Semistructured interviews with 42 nurses working in 11 Chinese cities were conducted, and their verbatim statements were transcribed and analysed using thematic analysis. The results were mapped to COM-B framework. RESULTS: Ten key themes emerged: Capability (professional knowledge and skills, emotional intelligence, cross-cultural care competence); opportunity (resources, organizational culture, social culture); motivation (past experience, character, role, beliefs). CONCLUSIONS: Ten factors were found to influence nurses' caring behaviour. This study added two new influencing factors, social culture and past experiences, that further contributed to the understanding of nurses' care behaviours. IMPLICATIONS FOR NURSING MANAGEMENT: Nurses' caring behaviour is influenced not only by themselves but also by institutions and society, so interventions aiming to improve their caring behaviour should consider these elements. The negative impact of the pandemic on capability factors that influence nurses' caring behaviour should be counteracted as soon as possible.

Discovery, synthesis, biological evaluation and structure-based optimization of novel piperidine derivatives as acetylcholine-binding protein ligands.

The homomeric α7 nicotinic receptor (α7 nAChR) is widely expressed in the human brain that could be activated to suppress neuroinflammation, oxidative stress and neuropathic pain. Consequently, a number of α7 nAChR agonists have entered clinical trials as anti-Alzheimer's or anti-psychotic therapies. However, high-resolution crystal structure of the full-length α7 receptor is thus far unavailable. Since acetylcholine-binding protein (AChBP) from Lymnaea stagnalis is most closely related to the α-subunit of nAChRs, it has been used as a template for the N-terminal domain of α-subunit of nAChR to study the molecular recognition process of nAChR-ligand interactions, and to identify ligands with potential nAChR-like activities.Here we report the discovery and optimization of novel acetylcholine-binding protein ligands through screening, structure-activity relationships and structure-based design. We manually screened in-house CNS-biased compound library in vitro and identified compound 1, a piperidine derivative, as an initial hit with moderate binding affinity against AChBP (17.2% inhibition at 100 nmol/L). During the 1st round of optimization, with compound 2 (21.5% inhibition at 100 nmol/L) as the starting point, 13 piperidine derivatives with different aryl substitutions were synthesized and assayed in vitro. No apparent correlation was demonstrated between the binding affinities and the steric or electrostatic effects of aryl substitutions for most compounds, but compound 14 showed a higher affinity (Ki=105.6 nmol/L) than nicotine (Ki=777 nmol/L). During the 2nd round of optimization, we performed molecular modeling of the putative complex of compound 14 with AChBP, and compared it with the epibatidine-AChBP complex. The results suggested that a different piperidinyl substitution might confer a better fit for epibatidine as the reference compound. Thus, compound 15 was designed and identified as a highly affinitive acetylcholine-binding protein ligand. In this study, through two rounds of optimization, compound 15 (Ki=2.8 nmol/L) has been identified as a novel, piperidine-based acetylcholine-binding protein ligand with a high affinity.

The heterogeneity of composition and assembly processes of the microbial community between different nutrient loading lake zones in Taihu Lake.

To investigate the differences in the microbial community composition and assembly process in two lake zones (Meiliang Bay (MLB) and Xukou Bay (XKB) in Taihu Lake, China) with different nutrient loadings, water samples were collected. Both the 16S ribosomal RNA (rRNA) gene for the bacterial community and the 18S rRNA gene for the microeukaryote community were investigated using the Illumina second-generation sequencing platform (2 × 250 paired-end). The results indicated that both the bacterioplankton and microeukaryote community composition derived from the two lake zones were significantly different. Significantly higher operational taxonomic unit (OTU) richness (P < 0.01) and phylogenetic diversity (P < 0.05) were found for the bacterioplankton community of MLB. However, a comparable alpha diversity was found between the microeukaryote communities of MLB and XKB (P > 0.05). Environmental factors significantly affected the community compositions in XKB for both the bacterioplankton and microeukaryotes. However, they did not significantly influence the microbial community composition in MLB, except for a weak correlation between dissolved organic carbon (DOC) and the microeukaryote community. The microbial communities tended to be more phylogenetically clustered than expected by chance in the two lake zones. Moreover, the results of the phylogenetic structure suggest that deterministic processes played overwhelming roles in driving the assembly of both the bacterioplankton and microeukaryote community in XKB.

Association between tertiary lymphoid structures and clinical outcomes in cancer patients treated with immune checkpoint inhibitors: an updated meta-analysis.

Background: Although numerous studies have reported the association between tertiary lymphoid structures (TLSs) and clinical outcomes in cancer patients treated with immune checkpoint inhibitors (ICIs), there remains a lack of a newer and more comprehensive meta-analysis. The main objective of this study is to explore prognostic biomarkers in immunotherapy-related patients, through analyzing the associations between tertiary lymphoid structures (TLSs) and clinical outcomes in cancer patients treated with ICIs, so as to investigate their prognostic value in cancer patients treated with ICIs. Methods: A comprehensive search was conducted until February 2024 across PubMed, Embase, Web of Science, and the Cochrane Library databases to identify relevant studies evaluating the association between tertiary lymphoid structures and clinical outcomes in cancer patients treated with ICIs. The clinical outcomes were overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). Results: Thirteen studies were incorporated in this meta-analysis, among which nine evaluated the prognostic value of TLSs. The results showed the high levels of TLSs predicted a significantly prolonged OS (pooled HR = 0.35, 95% CI: 0.24-0.53, p < 0.001) and PFS (pooled HR = 0.47, 95% CI: 0.31-0.72, p < 0.001), while lower ORR (pooled OR = 3.78, 95% CI: 2.26-6.33, p < 0.001) in cancer patients treated with ICIs. Conclusion: Our results indicated that high levels of TLSs could predict a favorable prognosis for cancer patients treated with ICIs and have the potential to become a prognostic biomarker of immunotherapy-related patients.

Trifolium repens L. recruits root-associated Microbacterium species to adapt to heavy metal stress in an abandoned Pb-Zn mining area.

Root-associated microbiota provide great fitness to hosts under environmental stress. However, the underlying microecological mechanisms controlling the interaction between heavy metal-stressed plants and the microbiota are poorly understood. In this study, we screened and isolated representative amplicon sequence variants (strain M4) from rhizosphere soil samples of Trifolium repens L. growing in areas with high concentrations of heavy metals. To investigate the microecological mechanisms by which T. repens adapts to heavy metal stress in abandoned mining areas, we conducted potting experiments, bacterial growth promotion experiments, biofilm formation experiments, and chemotaxis experiments. The results showed that high concentrations of heavy metals significantly altered the rhizosphere bacterial community structure of T. repens and significantly enriched Microbacterium sp. Strain M4 was demonstrated to significantly increased the biomass and root length of T. repens under heavy metal stress. Additionally, L-proline and stigmasterol could promote bacterial growth and biofilm formation and induce chemotaxis for strain M4, suggesting that they are key rhizosphere secretions of T. repens for Microbacterium sp. recruitment. Our results suggested that T. repens adapted the heavy metal stress by reshaping rhizosphere secretions to modify the rhizosphere microbiota.

Changes in soil microbe-mediated carbon, nitrogen and phosphorus cycling during spontaneous succession in abandoned PbZn mining areas.

The mechanism through which soil microorganisms mediate carbon and nutrient cycling during mine wasteland restoration remained unknown. Using soil metagenome sequencing, we investigated the dynamic changes in soil microbial potential metabolic functions during the transition from biological soil crusts (BSC) to mixed broad-conifer forest (MBF) in a typical PbZn mine. The results showed soil microorganisms favored carbon sequestration through anaerobic and microaerobic pathways, predominantly using efficient, low-energy pathways during succession. Genes governing carbon degradation and aerobic respiration increased by 19.56 % and 24.79 %, respectively, reflecting change toward more efficient and intensive soil carbon utilization in late succession. Nitrogen-cycling genes mediated by soil microorganisms met their maximum influence during early succession (sparse grassland, SGL), leading to a respective increase of 75.29 % and 76.81 % in the net potential nitrification rate and total nitrogen content. Mantel and correlation analyses indicated that TOC, TN, Zn and Cd contents were the main factors affecting the soil carbon and phosphorus cycles. Soil AP content emerged as the primary influencer of genes associated with the nitrogen cycle. These results shed light on the dynamic shifts in microbial metabolic activities during succession, providing a genetic insight into biogeochemical cycling mechanisms and underscoring crucial factors influencing soil biogeochemical processes in mining regions.

Empagliflozin alleviates neuroinflammation by inhibiting astrocyte activation in the brain and regulating gut microbiota of high-fat diet mice.

A high-fat diet can modify the composition of gut microbiota, resulting in dysbiosis. Changes in gut microbiota composition can lead to increased permeability of the gut barrier, allowing bacterial products like lipopolysaccharides (LPS) to enter circulation. This process can initiate systemic inflammation and contribute to neuroinflammation. Empagliflozin (EF), an SGLT2 inhibitor-type hypoglycemic drug, has been reported to treat neuroinflammation. However, there is a lack of evidence showing that EF regulates the gut microbiota axis to control neuroinflammation in HFD models. In this study, we explored whether EF could improve neuroinflammation caused by an HFD via regulation of the gut microbiota and the mechanism underlying this phenomenon. Our data revealed that EF alleviates pathological brain injury, reduces the reactive proliferation of astrocytes, and increases the expression of synaptophysin. In addition, the levels of inflammatory factors in hippocampal tissue were significantly decreased after EF intervention. Subsequently, the results of 16S rRNA gene sequencing showed that EF could change the microbial community structure of mice, indicating that the abundance of Lactococcus, Ligilactobacillus and other microbial populations decreased dramatically. Therefore, EF alleviates neuroinflammation by inhibiting gut microbiota-mediated astrocyte activation in the brains of high-fat diet-fed mice. Our study focused on the gut-brain axis, and broader research on neuroinflammation can provide a more holistic understanding of the mechanisms driving neurodegenerative diseases and inform the development of effective strategies to mitigate their impact on brain health. The results provide strong evidence supporting the larger clinical application of EF.

TRIM56 protects against nonalcoholic fatty liver disease by promoting the degradation of fatty acid synthase.

Nonalcoholic fatty liver disease (NAFLD) encompasses a disease continuum from simple steatosis to nonalcoholic steatohepatitis (NASH). However, there are currently no approved pharmacotherapies for NAFLD, although several drugs are in advanced stages of clinical development. Because of the complex pathophysiology and heterogeneity of NAFLD, the identification of potential therapeutic targets is clinically important. Here, we demonstrated that tripartite motif 56 (TRIM56) protein abundance was markedly downregulated in the livers of individuals with NAFLD and of mice fed a high-fat diet. Hepatocyte-specific ablation of TRIM56 exacerbated the progression of NAFLD, while hepatic TRIM56 overexpression suppressed it. Integrative analyses of interactome and transcriptome profiling revealed a pivotal role of TRIM56 in lipid metabolism and identified the lipogenesis factor fatty acid synthase (FASN) as a direct binding partner of TRIM56. TRIM56 directly interacted with FASN and triggered its K48-linked ubiquitination-dependent degradation. Finally, using artificial intelligence-based virtual screening, we discovered an orally bioavailable small-molecule inhibitor of FASN (named FASstatin) that potentiates TRIM56-mediated FASN ubiquitination. Therapeutic administration of FASstatin improved NAFLD and NASH pathologies in mice with an optimal safety, tolerability, and pharmacokinetics profile. Our findings provide proof of concept that targeting the TRIM56/FASN axis in hepatocytes may offer potential therapeutic avenues to treat NAFLD.

Bio-straw or not? Determinants of consumption intention under the plastic straw ban.

A new plastic ban has banned the use of single-use non-degradable plastic drinking straws in China's food and beverage industry by the end of 2020. However, this has caused widespread discussion and complaints on social media. What are consumers' reactions and what factors influence consumers to choose bio-straws (substitutes for plastic straws) are unclear. Therefore, this research collected 4367 effective comments (177,832 words in total) on "bio-straws" from social media and extracted keywords based on grounded theory to generate questionnaires. Structural equation modeling was used to analyze the consumption intention and influencing factors of 348 consumers regarding the ban. The results indicate the following: (1) consumer opinion on straws can be summarized into five main categories, namely, consumers' user experience, consumer subjectivity, policy awareness, policy acceptance, and consumption intention; (2) consumer subjectivity, policy awareness, and policy acceptance directly affect consumption intention significantly, while user experience affects consumption intention indirectly; and (3) user experience and consumer subjectivity play significant roles in mediating these relationships. From the perspective of consumers, this study provides an important basis for policymakers to formulate single-use plastic alternative policies in the future.

Shen Qi Wan attenuates renal interstitial fibrosis through upregulating AQP1.

Renal interstitial fibrosis (RIF) is the crucial pathway in chronic kidney disease (CKD) leading to the end-stage renal failure. However, the underlying mechanism of Shen Qi Wan (SQW) on RIF is not fully understood. In the current study, we investigated the role of Aquaporin 1 (AQP1) in SQW on tubular epithelial-to-mesenchymal transition (EMT). A RIF mouse model induced by adenine and a TGF-ß1-stimulated HK-2 cell model were etablished to explore the involvement of AQP 1 in the protective effect of SQW on EMT in vitro and in vivo. Subsequently, the molecular mechanism of SQW on EMT was explored in HK-2 cells with AQP1 knockdown. The results indicated that SQW alleviated kidney injury and renal collagen deposition in the kidneys of mice induced by adenine, increased the protein expression of E-cadherin and AQP1 expression, and decreased the expression of vimentin and α-smooth muscle actin (α-SMA). Similarly, treatmement with SQW-containing serum significantly halted EMT process in TGF-ß1 stimulated HK-2 cells. The expression of snail and slug was significantly upregulated in HK-2 cells after knockdown of AQP1. AQP1 knockdown also increased the mRNA expression of vimentin and α-SMA, and decreased the expression of E-cadherin. The protein expression of vimentin increased, while the expression of E-cadherin and CK-18 significantly decreased after AQP1 knockdown in HK-2 cells. These results revealed that AQP1 knockdown promoted EMT. Furthermore, AQP1 knockdown abolished the protective effect of SQW-containing serum on EMT in HK-2 cells. In sum, SQW attentuates EMT process in RIF through upregulation of the expression of AQP1.