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Abstract Background Inflammatory bowel disease (IBD) is a chronic, inflammatory, and autoimmune disorder, and its incidence of comorbid with major depressive disorder (MDD) is significantly higher than the general population. However, many patients lack proper recognition and necessary psychological health treatments. We aimed to identify potential biomarkers and mechanisms involved in the development of IBD comorbid with MDD (IBD-MDD). Methods We utilized IBD and MDD-related datasets from the GEO database for differential gene expression analysis, protein-protein interaction (PPI) and pathway enrichment analysis, random forest algorithm, LASSO regression analysis, and construction of a disease prediction model. We assessed the accuracy of the model using ROC curve, explored potential mechanisms through immune infiltration analysis, and validated candidate biomarkers using peripheral blood samples from patients in our center’s cohort. Results We identified 484 IBD-related secreted proteins and 142 key module genes associated with MDD. PPI analysis revealed two crucial modules primarily involved in inflammation and immune regulation. We identified four diagnostic genes (HGF, SPARC, ADAM12, and MMP8) from the 21 shared genes between IBD-related secreted proteins and MDD key module genes, constructed a nomogram model and confirmed its accuracy using ROC curve from an external independent dataset. Immune infiltration analysis revealed significant associations between the four diagnostic genes, and cellular immune dysregulation in MDD. Finally, we validated the expression patterns of the four diagnostic genes in our cohort. Conclusions Our study discovered four candidate biomarkers for IBD-MDD, providing new insights for the diagnosis and therapeutic intervention of serum-based IBD comorbid with MDD.

Entrustable Professional Activities-based (EPAs-based) assessments gained much interest among clinical educators, especially after the AAMC publication in 2014. In 2016, a standardized tool, the National Clinical Assessment Tool for Medical Students in Emergency Medicine (NCAT-EM), was developed at a national conference. Since 2018, the modified NCAT-EM has been used at Central Michigan University School of Medicine at shift ends, midway through clerkships, and upon completion of the clerkship. This empirical study analyzed student performance progression in order to enhance school assessment practices and inform future action plans. Descriptive and inferential statistics were calculated. During the 2021–2022 academic year, 89 faculty and residents assessed 97 students on 238 submission days. The students generally received multiple sets of daily shift feedback. Two domains, note writing and practice-based learning, showed significant differences between the mid-clerkship formative and summative scoring. Professionalism issues were evident with this cohort of students. The study provides some validity evidence regarding student performance and progression within the context. The NCAT-EM provides values and benefits as evidenced by the substantial volume of assessor feedback during its fourth year of implementation. This study provides directions for future action plans for faculty training, promising continuous improvement in emergency medicine assessment practices.

ABSTRACT E3 ubiquitin ligase (E3) plays a vital role in regulating inflammatory responses by mediating ubiquitination. Previous studies have shown that ankyrin repeat and SOCS box-containing protein 3 (ASB3) is involved in immunomodulatory functions associated with cancer. However, the impact of ASB3 on the dynamic interplay of microbiota and inflammatory responses in inflammatory bowel disease (IBD) is unclear. Here, we systematically identify the E3 ligase ASB3 as a facilitative regulator in the development and progression of IBD. We observed that ASB3 exhibited significant upregulation in the lesions of patients with IBD. ASB3−/− mice are resistant to dextran sodium sulfate-induced colitis. IκBα phosphorylation levels and production of proinflammatory factors IL-1β, IL-6, and TNF-α were reduced in the colonic tissues of ASB3−/− mice compared to WT mice. This colitis-resistant phenotype was suppressed after coprophagic microbial transfer and reversed after combined antibiotics removed the gut commensal microbiome. Mechanistically, ASB3 specifically catalyzes K48-linked polyubiquitination of TRAF6 in intestinal epithelial cells. In contrast, in ASB3-deficient organoids, the integrity of the TRAF6 protein is shielded, consequently decelerating the onset of intestinal inflammation. ASB3 is associated with dysregulation of the colitis microbiota and promotes proinflammatory factors’ production by disrupting TRAF6 stability. Strategies to limit the protein level of ASB3 in intestinal epithelial cells may help in the treatment of colitis.IMPORTANCEUbiquitination is a key process that controls protein stability. We determined the ubiquitination of TRAF6 by ASB3 in intestinal epithelial cells during colonic inflammation. Inflammatory bowel disease patients exhibit upregulated ASB3 expression at focal sites, supporting the involvement of degradation of TRAF6, which promotes TLR-Myd88/TRIF-independent NF-κB aberrant activation and intestinal microbiota imbalance. Sustained inflammatory signaling in intestinal epithelial cells and dysregulated protective probiotic immune responses mediated by ASB3 collectively contribute to the exacerbation of inflammatory bowel disease. These findings provide insights into the pathogenesis of inflammatory bowel disease and suggest a novel mechanism by which ASB3 increases the risk of colitis. Our results suggest that future inhibition of ASB3 in intestinal epithelial cells may be a novel clinical strategy.

Abstract Background Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a familial cardiac disease associated with ventricular arrhythmias and an increased risk of sudden cardiac death. Currently, there are no approved treatments that address the underlying genetic cause of this disease, representing a significant unmet need. Mutations in Plakophilin-2 (PKP2), encoding a desmosomal protein, account for approximately 40% of ARVC cases and result in reduced gene expression. Methods Our goal is to examine the feasibility and the efficacy of adeno-associated virus 9 (AAV9)-mediated restoration of PKP2 expression in a cardiac specific knock-out mouse model of Pkp2. Results We show that a single dose of AAV9:PKP2 gene delivery prevents disease development before the onset of cardiomyopathy and attenuates disease progression after overt cardiomyopathy. Restoration of PKP2 expression leads to a significant extension of lifespan by restoring cellular structures of desmosomes and gap junctions, preventing or halting decline in left ventricular ejection fraction, preventing or reversing dilation of the right ventricle, ameliorating ventricular arrhythmia event frequency and severity, and preventing adverse fibrotic remodeling. RNA sequencing analyses show that restoration of PKP2 expression leads to highly coordinated and durable correction of PKP2-associated transcriptional networks beyond desmosomes, revealing a broad spectrum of biological perturbances behind ARVC disease etiology. Conclusions We identify fundamental mechanisms of PKP2-associated ARVC beyond disruption of desmosome function. The observed PKP2 dose-function relationship indicates that cardiac-selective AAV9:PKP2 gene therapy may be a promising therapeutic approach to treat ARVC patients with PKP2 mutations.

Objective The internet has become a preferred source for people seeking health information, including diet recommendations which are pivotal in the management of inflammatory bowel disease (IBD). Hence, we aimed to assess the quality of online information in China regarding IBD dietary recommendations. Methods The search engines Baidu and Bing were used to screen for their top 25 webpages using the keywords “inflammatory bowel disease diet,” “ulcerative colitis diet,” “Crohn's disease diet,” “inflammatory bowel disease nutrition,” “ulcerative colitis nutrition,” and “Crohn's disease nutrition.” The quality of information was assessed by two physicians according to the Journal of the American Medical Association (JAMA) benchmark, the Global Quality Score (GQS), and the DISCERN instrument. Results One hundred and eight webpages were selected for evaluation. The mean scores for JAMA, GQS, and DISCERN were 1.48, 3.11, and 36.20, respectively. Articles from professionals and non-profit organizations demonstrated superior quality compared to those from commercial and health portal websites. Many webpages failed to provide an explicit source of information or support for shared decision-making. The information on several pages lacked comprehensive descriptions of food types for IBD, with some pages even containing inaccuracies. No statistically significant differences in scores were observed between Baidu and Bing. Conclusions The quality of online information on IBD dietary recommendations in China is moderate to low and exhibits significant variation across different sources. This warrants joint efforts from online authors, internet platforms, and regulators, to improve the quality of popular medical information.

Cadmium (Cd) contamination poses a significant threat to agricultural soils and food safety, necessitating effective remediation strategies. Salix species, with their high coverage and Cd accumulating capacity, hold promise for remediation efforts. The rhizosphere microbiome is crucial for enhancing Cd accumulating capacity for Salix. However, the mechanisms by how Salix interacts with its rhizosphere microbiome to enhance Cd extraction remains poorly understood. In this study, we compared the remediation performance of two Salix ecotypes: 51–3 (High Cd-accumulating Ecotype, HAE) and P646 (Low Cd-accumulating Ecotype, LAE). HAE exhibited notable advantages over LAE, with 10.80 % higher plant height, 43.80 % higher biomass, 20.26 % higher Cd accumulation in aboveground tissues (93.09 μg on average), and a superior Cd translocation factor (1.97 on average). Analysis of the rhizosphere bacterial community via 16S rRNA amplicon sequencing revealed that HAE harbored a more diverse bacterial community with a distinct composition compared to LAE. Indicator analysis identified 84 genera specifically enriched in HAE, predominantly belonging to Proteobacteria, Actinobacteria, and Firmicutes, including beneficial microbes such as Streptomyces, Bacillus, and Pseudomonas. Network analysis further elucidated three taxa groups specifically recruited by HAE, which were highly correlated with functional genes that associated with biosynthesis of secondary metabolites, glycan biosynthesis and metabolism, and metabolism of cofactors and vitamins. These functions contribute to enhancing plant growth, Cd uptake, and resistance to Cd in Salix. Overall, our findings highlight the importance of the rhizosphere microbiome in facilitating Cd extraction and provide insights into microbiome-based strategies for sustainable agricultural practices.

Abstract Heart failure with preserved ejection fraction (HFpEF) poses therapeutic challenges due to the limited treatment options. Building upon our previous research that demonstrates the efficacy of histone deacetylase 6 (HDAC6) inhibition in a genetic cardiomyopathy model, we investigate HDAC6’s role in HFpEF due to their shared mechanisms of inflammation and metabolism. Here, we show that inhibiting HDAC6 with TYA-018 effectively reverses established heart failure and its associated symptoms in male HFpEF mouse models. Additionally, in male mice lacking Hdac6 gene, HFpEF progression is delayed and they are resistant to TYA-018’s effects. The efficacy of TYA-018 is comparable to a sodium-glucose cotransporter 2 (SGLT2) inhibitor, and the combination shows enhanced effects. Mechanistically, TYA-018 restores gene expression related to hypertrophy, fibrosis, and mitochondrial energy production in HFpEF heart tissues. Furthermore, TYA-018 also inhibits activation of human cardiac fibroblasts and enhances mitochondrial respiratory capacity in cardiomyocytes. In this work, our findings show that HDAC6 impacts on heart pathophysiology and is a promising target for HFpEF treatment.

ABSTRACT: Managing pediatric Crohn's disease (PCD) presents challenges due to severe complications and higher biologic therapy needs. Transitioning from anti–tumor necrosis factor agents to off-label therapies adds complexity. Although upadacitinib has demonstrated efficacy and tolerability in adult inflammatory bowel disease and pediatric atopic dermatitis, there are limited data for its application in PCD. This case report delineates successful remission with upadacitinib in a child with CD refractory to infliximab, ustekinumab, adalimumab, thalidomide, and prednisone. Notably, the patient carried an ataxia telangiectasia mutated (ATM) gene mutation. These findings provide valuable evidence for PCD management and highlight the potential benefits of upadacitinib in this population.

Heavy metal (HM)-induced stress can lead to the enrichment of HMs in plants thereby threatening people’s lives and health via the food chain. For this reason, there is an urgent need for some reliable and practical techniques to detect and analyze the absorption, distribution, accumulation, chemical form, and transport of HMs in plants for reducing or regulating HM content. Not only does it help to explore the mechanism of plant HM response, but it also holds significant importance for cultivating plants with low levels of HMs. Even though this field has garnered significant attention recently, only minority researchers have systematically summarized the different methods of analysis. This paper outlines the detection and analysis techniques applied in recent years for determining HM concentration in plants, such as inductively coupled plasma mass spectrometry (ICP-MS), atomic absorption spectrometry (AAS), atomic fluorescence spectrometry (AFS), X-ray absorption spectroscopy (XAS), X-ray fluorescence spectrometry (XRF), laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS), non-invasive micro-test technology (NMT) and omics and molecular biology approaches. They can detect the chemical forms, spatial distribution, uptake and transport of HMs in plants. For this paper, the principles behind these techniques are clarified, their advantages and disadvantages are highlighted, their applications are explored, and guidance for selecting the appropriate methods to study HMs in plants is provided for later research. It is also expected to promote the innovation and development of HM-detection technologies and offer ideas for future research concerning HM accumulation in plants.

The genus Schisandra belongs to the family Schisandraceae and grows mainly in south-central and southwestern China. Most of the plants in this genus are used for medicine by their fruits, usually for the treatment of inflammatory diseases. In traditional medicine, Schisandra is also used to stop bleeding, relieve pain, and clear heat. Based on this, many domestic and foreign scholars have conducted systematic studies on its chemical composition, and experimental data show that triterpenoid components are the important material basis for the pharmacological effects of this genus. This paper summarizes the relevant literature on triterpenes of the genus Schisandra from 1983 to 2023. All information and research about this paper was obtained from libraries and digital databases (SciFinder, Medline PubMed, Google Scholar, and CNKI, etc.). At present, there are 335 different kinds of triterpenes isolated from the genus Schisandra, including lanostanes, cycloartanes, nortriterpenoids and pentacyclic triterpenoids, which are mostly found in fruits and vine stems. They have been found to possess various activities such as antitumor, antioxidant, anti-inflammatory, immunomodulatory, neuroprotective, nephroprotective and hepatoprotective.This review systematically summarizes the literature on triterpenoid composition, traditional applications, pharmacology, and exploitation of the genus Schisandra. We hope this paper will provide a valuable reference for further research and development of the resources of this genus.

Objectives: The ocean is a huge ecosystem with diverse marine life. Scientists have found a large number of natural products with unique structural features and excellent biological activity from these organisms. Marine-derived sulphur-containing alkaloids are a significant family of natural products with diverse structures and bioactivities. In this paper, the chemical and biological diversity of 972 sulfur-containing alkaloids derived from marine organisms reported from 1982 to 2022 were reviewed, and the structure–activity relationship was briefly analyzed, in order to provide reference for the discovery, synthesis, biological activity research and drug development of such compounds. Key findings: A total of 972 marine-derived sulphur-containing alkaloids have been collected. Among them, 80.36% of sulphur-containing alkaloids are from marine sponges, fungi, tunicates and bacteria. Moreover, cytotoxicity is their most significant property, About 1/3 sulphur-containing organisms are reported to be cytotoxic. Aming them, discorhabdins, curacins, tanjungides, leptosins, and latrunculins exhibit better cytotoxicity. In addition, the structure–activity relationships of the cytotoxicity of these compounds have been summarized for further investigation. Summary: In this paper, the chemical and bioactivity diversity of marine-derived sulphur-containing alkaloids were reviewed, which are a significant family of natural products with diverse structures and bioactivities. 972 sulphur-containing alkaloids were obtained from marine algae, sponges, cnidarians, tunicates, echinoderms, molluscs, bryozoans, dinoflagellates, cyanobacteria, bacteria and fungi, which possessed a wide spectrum of pharmacology including cytotoxicity, antibacterial, antifungal, antimitotic, antiviral, and other activities.

Carbapenem-resistant Pseudomonas aeruginosa (CRPA) has been a major threat to human health due to its increased morbidity and mortality in clinical settings. Carbapenemase genes are less frequently found in CRPA compared with carbapenem-resistant Enterobacterales, of which carbapenemase producers are common. In this study, we identified 11 blaKPC-2-harbouring P. aeruginosa isolates from 139 carbapenemase-insensitive P. aeruginosa isolates collected between 2010 and 2021 in a tertiary hospital in China. Nine isolates belonged to ST697, while the other two were ST463. The antibiotic susceptibility testing showed that all the isolates were multidrug resistant, including resistance to imipenem, meropenem, ceftazidime, and tigecycline. Patients with Klebsiella pneumoniae carbapenemase-2 (KPC-2)-producing P. aeruginosa infections were mostly associated with complicated diseases and prolonged hospital stay, with 30% deterioration. The whole-genome sequencing analysis showed that these isolates carried multiple antibiotic resistance genes and virulence genes, and the KPC-2 genetic elements were highly related in ST697 isolates. The complete sequencing of ST697 isolate SE5416 showed that the harbouring of blaKPC-2 resulted from complex transposition and homologous recombination of an IncpRBL16 plasmid and other mobile elements. The Galleria mellonella infection model experiment showed that these KPC-2-producing P. aeruginosa–infected larvae had low survival rates and high virulence. The present study revealed the shifting of CRPA from ST697 to ST463 in East China; ST463 had higher drug resistance, posing greater challenges for clinical management.

Blockchain is widely used in the manufacturing industry. This paper establishes a dual-channel supply chain composed of a manufacturer and an e-retailer. A monopoly manufacturer conducts indirect online selling through retailers as well as direct offline selling. The manufacturer chooses to adopt a self-built blockchain traceability system (SBT) or a third-party blockchain traceability system (TBT). Game analysis is developed to depict the pricing decision for the manufacturer and e-retailer. The optimal pricing decisions of the supply chain between manufacturer and e-retailer for different blockchain traceability strategies are obtained. We explore the influence of consumers’ traceability awareness on the decisions of dual-channel supply chain members when adopting different blockchain traceability strategies. The main results show that when the fee paid to the blockchain service provider is low, the manufacturer will prefer to adopt TBT. Moreover, we prove that consumers’ traceability awareness, the cost of adopting TBT, the blockchain traceability technology level, and the research and development cost factor of blockchain technology could affect the decisions of supply chain members. Finally, some management suggestions are provided.

Background and AimsResearch on the effect of the coronavirus disease 2019 (COVID-19) pandemic on psychosocial function in patients with pediatric-onset inflammatory bowel disease (PIBD) is limited. This study aimed to evaluate the psychological status of patients with PIBD before and during the pandemic, and the relationship between mental health and disease activity.MethodsThis study was a retrospective cohort study. Statistical analyses were performed to assess the relationship between demographic, clinical data and psychological data (questionnaires) of PIBD patients before and during the epidemic. The anxiety and depression emotional status of the guardians during the pandemic were evaluated.ResultsIn the PIBD follow-up cohort, 42 patients(male 61.9%) were included. Female with PIBD had lower pediatric quality of life inventory(PedsQL) scores (P = 0.007) and higher spence children's anxiety scale(SCAS) scores (P = 0.038) than male. The pandemic did not have a substantial impact on PedsQL, pittsburgh sleep quality index(PSQI), SCAS, or children's depression inventory(CDI) in patients with PIBD. The self-rating anxiety scale(SAS) score, anxiety rate, self-rating depression scale(SDS) score, and depression rate of PIBD guardians were significantly higher than those of healthy controls (SAS, P = 0.008; SDS, P = 0.001).ConclusionsFemale children with PIBD were more vulnerable to decreased QOL and increased anxiety than male children. The anxiety and depression status of PIBD guardians were significantly higher than those of healthy controls during the COVID-19 pandemic. But the COVID-19 pandemic did not significantly affect quality of life(QOL), sleep, anxiety, or depressive mood of patients with PIBD in our study.

Cytokines play vital roles in the pathogenesis of inflammatory bowel disease. IL17B is protective in the development of colitis. However, how IL17B regulates intestinal inflammation and what cells are regulated by IL17B is still unknown. Here, we aimed to illustrate the IL17B dependent cellular and molecular changes in colon tissue in a mouse colitis model. The results showed that IL17B expression in colon tissues was elevated in inflamed tissues than non-inflamed tissues of IBD patients. Wild type (WT) and Il17b deficient (Il17b-/-) mice were given 2.5% dextran sodium sulfate (DSS) water, and in some case, Il17b-/- mice were treated with recombinant mouse IL17B. IL17B deficiency resulted in severe DSS-induced colitis with exaggerated weight loss, shorter colon length, and elevated proinflammatory cytokines in colon. Reconstitution of Il17b-/- mice with recombinant IL17B alleviated the severity of DSS-induced colitis. Single cell transcriptional analyses of CD45+ immune cells in colonic lamina propria revealed that loss of IL17B resulted in an increased neutrophil infiltration and enhanced inflammatory cytokines in intestinal macrophages in colitis, which were confirmed by real-time PCR and flow cytometry. IL17B treatment also inhibited lipopolysaccharide-induced inflammation in bone marrow-derived macrophages and mice. IL17B inhibits colitis by regulating colonic myeloid cell response. It might represent a novel potential therapeutic approach to treat the colitis.

Background. The relationship between vitamin D (vit-D) levels and the effectiveness of infliximab (IFX) in patients with Crohn’s disease (CD) remains controversial. Objective. To evaluate the interaction between vit-D levels and the response to IFX therapy in patients with CD. Methods. This was a retrospective cohort study. Serum vit-D and IFX trough concentrations (TC) were measured in 84 patients, and statistical analyses were performed. Results. The total vit-D deficiency rate at enrollment, at week 14 and week 38, was 64.3%, 41.67%, and 37.5%, respectively (P

Grinding is a critical surface-finishing process in the manufacturing industry. One of the challenging problems is that the specific grinding energy is greater than in ordinary procedures, while energy efficiency is lower. However, an integrated energy model and analysis of energy distribution during grinding is still lacking. To bridge this gap, the grinding time history is first built to describe the cyclic movement during air-cuttings, feedings, and cuttings. Steady and transient power features during high-speed rotations along the spindle and repeated intermittent feeding movements along the x-, y-, and z-axes are also analysed. Energy prediction models, which include specific movement stages such as cutting-in, stable cutting, and cutting-out along the spindle, as well as infeed and turning along the three infeed axes, are then established. To investigate model parameters, 10 experimental groups were analysed using the Gauss-Newton gradient method. Four testing trials demonstrate that the accuracy of the suggested model is acceptable, with errors of 5%. Energy efficiency and energy distributions for various components and motion stages are also analysed. Low-power chip design, lightweight worktable utilization, and minimal lubricant quantities are advised. Furthermore, it is an excellent choice for optimizing grinding parameters in current equipment.

Abstract Background Dendrobium is a precious herbal that belongs to Orchidaceae and is widely used as health care traditional Chinese medicine in Asia. Although orchids are mycorrhizal plants, most research still focuses on endophytes, and there is still large amount unknown about rhizosphere microorganisms. To investigate the rhizosphere microbial community of different Dendrobium species during the maturity stage, we used high-throughput sequencing to analyze microbial community in rhizosphere soil during the maturity stage of three kinds of Dendrobium species. Results In our study, a total of 240,320 sequences and 11,179 OTUs were obtained from these three Dendrobium species. According to the analysis of OTU annotation results, different Dendrobium rhizosphere soil bacteria include 2 kingdoms, 63 phyla, 72 classes, 159 orders, 309 families, 850 genera and 663 species. Among all sequences, the dominant bacterial phyla (relative abundance > 1%) were Proteobacteria, Actinobacteria, Bacteroidetes, Acidobacteria, Firmicutes, Verrucomicrobia, Planctomycetes, Chloroflexi, and Gemmatimonadetes. And through WGCNA analysis, we found the hub flora was also belong to Acidobacteria, Actinobacteria and Proteobacteria. Conclusions We found that the rhizosphere bacterial communities of the three kinds of Dendrobium have significant differences, and that the main species of rhizosphere microorganisms of Dendrobium are concentrated in the Proteobacteria, Actinobacteria, and Bacteroidetes. Moreover, the smaller the bacterial level, the greater the difference among Dendrobium species. These results fill knowledge gaps in the rhizosphere microbial community of Dendrobium and provide a theoretical basis for the subsequent mining of microbial functions and the study of biological fertilizers.

Abstract Background Diabetic retinopathy (DR) involves extensive retinal damage and is one of the most common and serious complications of diabetes mellitus. Hyperglycemia is the major pathological trigger for diabetic complications. Müller cell gliosis, a key pathophysiological process in DR, could finally lead to vision loss. Our previous finding revealed that the essential oil of Fructus Alpiniae zerumbet (EOFAZ) protects human umbilical vein endothelial cells (HUVECs) against high glucose (HG)-induced injury via the PPAR-γ signal. However, Whether EOFAZ could prevent HG-induced Müller cell gliosis through the PPAR signaling remains unclear. Methods The neuroprotective effects of EOFAZ were evaluated in HG-treated rat retinal Müller cells (RMCs) and DR rat model. Result GFAP and VEGF upregulation is the biomarker of Müller glial reactivity gliosis. Results suggested that EOFAZ could remarkably ameliorate retinal reactive gliosis by suppressing p-CREB and GFAP and VEGF downstream effectors. Its effects on PPAR-γ, a major target for currently available anti-diabetes drugs, were also investigated. EOFAZ treatment remarkably attenuated the reduction of PPAR-γ and high level of p-CaMK II and p-CREB in HG-treated RMCs and diabetic rats. Furthermore, the activation and ectopic expression of PPAR-γ downregulated p-CREB and p-CaMK II in HG-treated RMCs. By contrast, CaMK II inhibitor KN93 and CREB gene silencing did not significantly affect the PPAR-γ expression. Conclusions A novel PPAR-γ-p-CREB signaling pathway accounts for the inhibitory effect of EOFAZ on RMCs gliosis. These findings provide scientific evidence for the potential use of EOFAZ as a complementary and alternative medicine for DR prevention and treatment in the future.

Blockchain technology allows fresh agricultural enterprises to share records stored on the chain, and the technology can benefit information management systems, such as decentralization and transparency. This study uses game theory to examine a blockchain introduction strategy for fresh agricultural enterprises in a competitive environment, considering consumer traceability preferences. We establish a pricing decision model in traditional and blockchain traceability modes and identify optimal solutions. Additionally, we analyze the impact of the blockchain introduction strategy, consumer preferences, and blockchain influence factor on optimal pricing decisions. The results indicate that the introduction of blockchain could improve the profits of enterprises under certain conditions. Moreover, consumer traceability preferences and the blockchain influence factor could significantly affect the blockchain introduction strategy. We also discover that when the blockchain influence factor meets a certain range, introducing blockchain technique in the traceability system could shift demand from traditional enterprises to blockchain enterprises. The total market demand for blockchain enterprises under the blockchain traceability mode will increase, whereas that of traditional enterprises under the blockchain traceability mode will decrease. Both consumer traceability preferences and the blockchain influence factor could significantly affect optimal pricing. Finally, some management suggestions are provided for the traceability of fresh agricultural enterprises based on the research conclusions.

Abstract Although long noncoding RNAs (lncRNAs) do not have protein coding capacities, they are involved in the pathogenesis of many types of cancers, including hepatocellular carcinoma, cervical cancer, and gastric cancer. Notably, the roles of lncRNAs are vital in nearly every aspect of tumor biology. Long non‐coding small nucleolar RNA host genes (lnc‐SNHGs) are abnormally expressed in multiple cancers, including urologic neoplasms, respiratory tumors, and digestive cancers, and play vital roles in these cancers. These host genes could participate in tumorigenesis by regulating proliferation, migration, invasion and apoptosis of tumor cells. This review focuses on the overview of the roles that lnc‐SNHGs play in the formation and progression of digestive cancers.

Medical educators and programs are deeply interested in understanding and projecting the longitudinal developmental trajectories of medical students after these students are matriculated into medical schools so appropriate resources and interventions can be provided to support students' learning and progression during the process. As students have different characteristics and they do not learn and progress at the same pace, it is important to identify student subgroups and address their academic needs to create more equitable learning opportunities. Using latent class growth analysis, this study explored students' developmental trajectories and detected group differences based on their coursework performance in Anatomy within the two years of preclinical education in one medical school. Four subgroups were identified with various intercepts and slopes. There were significant group differences between these subgroups and their standardized scores in MCAT and UCMLE Step 1. The study provides evidence about the heterogeneity of the student population and points out future research directions.

The excess amounts of heavy metals are toxic to various physiological processes in plants. Plant metallothioneins (MTs) are low molecular weight, cysteine-rich metal-binding proteins that play important roles in the detoxification of heavy metal ions. In this study, we characterized CsMT4, a plant type 4 MT gene identified in a complementary DNA (cDNA) library prepared from young cucumber (Cucumis sativus) fruit. CsMT4 encodes a 90 amino acid protein with a predicted molecular mass of 9.028 kD. CsMT4 contains 17 cysteine residues in three highly conserved cysteine-rich domains. In contrast to the structures of other MTs, the highly conserved amino acid pattern CxCxxxCxCxxCxC is present in the middle of CsMT4. Furthermore, CsMT4 was markedly induced in various tissues by various concentrations of Cd2+ and Zn2+ (> 1.0 mmol•L−1). Similar to AtMT4b function, heterologous expression of CsMT4 in E. coli could also improved its tolerance to Cd2+ and led to increased uptake of Cd2+, and the rate of Cd2+ uptake was the highest in cells expressing a phytochelatin-like peptide. Our findings demonstrate that CsMT4 might be obviously induced by the metal stress in cucumber, and improves tolerance to Cd ions but not Zn ions when heterologously expressed in E. coli, and suggest that the composition and arrangement of N-terminal Cys-residues in MT4 are associated with their binding capacity and preference for different metal ions. Keywords: Cucumber, CsMT4, Metallothionein, Metal-binding properties, Heterologous expression

To determine factors that influence faculty engagement and success in faculty learning communities focused on collaborative Scholarship of Teaching and Learning (SoTL), our project gathered information on (1) faculty motivation to engage with SoTL; (2) structures that support collaboration; (3) the perceived impact of SoTL on teaching, scholarship, and faculty engagement in academic communities on campus and beyond; and (4) the role of the teaching center in supporting collaborative faculty learning communities focused on SoTL. In this explanatory, sequential design mixed-methods study, participants were asked to complete a survey on their experience as participants in faculty learning communities at a large comprehensive public university in the southeastern United States; researchers then conducted one-on-one interviews with select participants to gain an in-depth understanding of trends and questions emerging from the survey data. Results indicate that personal, institutional, professional, and team factors contribute to participants’ perception of the success and effectiveness of collaborative research teams. Findings from the study offer guidance for setting up effective collaborative structures for SoTL projects and nurturing inter-disciplinary research among faculty members, thus providing insights that can inform the design and facilitation of similar programs in the United States and internationally.

Herbaceous peony (Paeonia lactiflora Pall.) flowers can be used as edible flowers, but few studies concerned about their edible values and the optimal harvest season. In this study, petals of three herbaceous peony cultivars including “Dafugui,” “Hongyan Zhenghui,” and “Yangfei Chuyu” at four different development stages were used as materials to measure the content of soluble sugar, organic acid, protein, vitamin C (Vc), total phenolics, total flavonoids, mineral elements, and superoxide dismutase (SOD) activity, with the aim to understand the variation tendency of the nutritional ingredients and bioactive components in herbaceous peony flower petals during development and to determine the optimal harvest time for herbaceous peony flowers with better edible qualities. The results demonstrated that the content of individual nutritional and bioactive components was varied with cultivars and developmental stages. The soluble sugar content was 63.69–225.97 mg/g FW, organic acid 10.13–24.60 mg/g FW, soluble protein 9.83–39.17 mg/g FW, Vc 12.31–33.52 mg/100 g FW, total phenolics 83.23–136.19 mg/g DW, total flavonoids 10.20–24.98 mg/g DW, and SOD activity 62.92–284.09 U/g FW. For mineral elements, the content of Na, Mg, K, Ca, Mn, Fe, Ni, and Zn was 20.96–65.51 μg/g DW, 810.85–1342.36 μg/g DW, 6723.68–12253.63 μg/g DW, 848.67–3038.46 μg/g DW, 1.14–8.44 μg/g DW, 48.70–149.72 μg/g DW, 1.20–2.17 μg/g DW, and 16.69–25.50 μg/g DW, respectively. The content of soluble sugar, protein, total flavonoids, and SOD activity in flower petals was the highest, and the content of organic acid was the lowest at the full bloom period (S3) for all three cultivars, while the highest Vc and total phenolics were at the early bloom stage (S2) and flower bud stage (S1), respectively. In conclusion, it is recommended to harvest herbaceous peony flowers at S3 with the best edible quality considering nutrients and bioactive components.

Two new furostanol saponins 1–2 and a new spirostanol saponin 3 were isolated together with two known furostanol saponins 4–5 from the roots and rhizomes of Tupistra chinensis. Their structures were characterized as 1β,2β,3β,4β,5β,26-hexahydroxyfurost-20(22), 25(27)-dien-5,26-O-β-d-glucopyranoside (1), 1β,2β,3β,4β,5β,6β,7α,23ξ,26-nona-hydroxyfurost- 20(22),25(27)-dien-26-O-β-d-glucopyranoside (2), (20S,22R)-spirost-25 (27)-en-1β,3β,5β- trihydroxy-1-O-β-d-xyloside (3), tupisteroide B (4) and 5β-furost-Δ25(27)-en-1β,2β,3β,4β,5β,7α, 22ξ,26-octahydroxy-6-one-26-O-β-d-glucopyranoside (5), respectively, by extensive use of spectroscopic techniques and chemical evidence. Additionally, the in vitro cytotoxic activity of 1–4 was evaluated on human A549 and H1299 tumor cell lines, and compound 3 exhibited cytotoxicity against A549 cells (IC50 86.63 ± 2.33 μmol·L−1) and H1299 cells (IC50 88.21 ± 1.34 μmol·L−1).

Three new C19-norditerpenoid alkaloids (1–3), along with two known C19-norditerpenoid alkaloids (4,5), have been isolated from Aconitum szechenyianum. Based on extensive spectroscopic techniques (1D, 2D-NMR, IR, and MS) and chemical methods, their structures were established as szechenyianine D (1), szechenyianine E (2), szechenyianine F (3), 8-O-methyl-14-benzoylaconine (4), and spicatine A (5). The immunosuppressive effects of compounds 1–5 were studied using a ConA-induced or LPS-induced splenocyte proliferation model. In vitro tests showed that Compounds 2, 4, and 5 suppressed ConA-induced or LPS-induced splenocyte proliferation in a concentration-dependent manner. The CC50/IC50 values of 2, 4, and 5 suggested that these compounds were potential immunosuppressive agents for the treatment of autoimmune diseases characterized by arthritis, such as rheumatoid arthritis.

Four new steroidal constituents (1–4) along with two known steroidal glycosides (5 and 6) were isolated from the roots and rhizomes of Smilacina japonica. Analysis of their physicochemical properties and spectroscopic profiles identified the compounds as (25S)-5α-spirostan-9(11)-en-3β, 17α-diol (1); (25S)-5α-spirostan-9(11)-en-3β, 12β-diol (2); (25S)-5α-spirostan-9(11)-en-3β, 17α-diol-3-O-β-d-glucopyranoside (3); (25S)-5α-spirostan-9(11)-en-3β, 17α-diol-3-O-β-d-glucopyranosyl-(1→2)-[β-d-glucopyranosyl-(1→3)]-β-d-galactopyranoside (4); japonicoside B (5); and japonicoside C (6). All six compounds showed cytotoxic activity against SMMC-7712, Bel-7402, A549, H460, and K562 human cancer cells.

Insulin increases cellular glucose uptake and metabolism in the postprandial state by acutely stimulating the translocation of the Glut4 glucose transporter from intracellular membrane compartments to the cell surface in muscle and fat cells. The intracellular targeting of Glut4 is dictated by specific structural motifs within cytoplasmic domains of the transporter. We demonstrate that two leucine residues at the extreme C-terminus of Glut4 are critical components of a motif (IRM, insulin responsive motif) involved in the sorting of the transporter to insulin responsive vesicles in 3T3L1 adipocytes. Light microscopy, immunogold electron microscopy, subcellular fractionation, and sedimentation analysis indicate that mutations in the IRM cause the aberrant targeting of Glut4 to large dispersed membrane vesicles that are not insulin responsive. Proteomic characterization of rapidly and slowly sedimenting membrane vesicles (RSVs and SSVs) that were highly enriched by immunoadsorption for either wild-type Glut4 or an IRM mutant revealed that the major vesicle fraction containing the mutant transporter (IRM-RSVs) possessed a relatively small and highly distinct protein population that was enriched for proteins associated with stress granules. We suggest that the IRM is critical for an early step in the sorting of Glut4 to insulin-responsive subcellular membrane compartments and that IRM mutants are miss-targeted to relatively large, amorphous membrane vesicles that may be involved in a degradation pathway for miss-targeted or miss-folded proteins or represent a transitional membrane compartment that Glut4 traverses en route to insulin responsive storage compartments.

Three new C19-norditerpenoid alkaloids (1–3), along with two known C19-norditerpenoid alkaloids (4–5) have been isolated from Aconitum szechenyianum. Their structures were established by extensive spectroscopic techniques and chemical methods as szechenyianine A (1), szechenyianine B (2), szechenyianine C (3), N-deethyl-3-acetylaconitine (4), and N-deethyldeoxyaconitine (5). Additionally, compounds 1–5 were tested for the inhibition of NO production on LPS-activated RAW264.7 cells with IC50 values of 36.62 ± 6.86, 3.30 ± 0.11, 7.46 ± 0.89, 8.09 ± 1.31, and 11.73 ± 1.94 μM, respectively, while the positive control drug dexamethasone showed inhibitory activity with IC50 value of 8.32 ± 1.45 μM. The structure-activity relationship of aconitine alkaloids were discussed.

Motivation, an important characteristic of the learner, is related to several key educational outcomes, such as persistence; performance; learning quality; and psychological well-being. Self-determination theory posits that human behaviors are either intrinsically motivated, extrinsically motivated, or amotivated. Using a self-reported questionnaire within the framework of self-determination theory, this study examined the motivational styles of Canadian Master’s of Education learners. Results indicated that this group of learners reported using more self-determined motivational styles. The age of the participants was a factor in that the participants who were more advanced in age reported less frequently that they perceived a locus of control for their academic learning from external sources. Part-time and full-time learners showed significant differences in terms of amotivation and identified regulation, indicating that part-time learners were more motivated than full-time students. By clarifying motivational styles used by graduate students, the study provides educational implications for graduate programs and adult education.