Regulation by distinct MYB transcription factors defines the roles of OsCYP86A9 in anther development and root suberin deposition.

Cytochrome P450 proteins (CYPs) play critical roles in plant development and adaptation to fluctuating environments. Previous reports have shown that CYP86A proteins are involved in the biosynthesis of suberin and cutin in Arabidopsis. However, the functions of these proteins in rice remain obscure. In this study, a rice mutant with incomplete male sterility was identified. Cytological analyses revealed that this mutant was defective in anther development. Cloning of the mutant gene indicated that the responsible mutation was on OsCYP86A9. OsMYB80 is a core transcription factor in the regulation of rice anther development. The expression of OsCYP86A9 was abolished in the anther of osmyb80 mutant. In vivo and in vitro experiments showed that OsMYB80 binds to the MYB-binding motifs in OsCYP86A9 promoter region and regulates its expression. Furthermore, the oscyp86a9 mutant exhibited an impaired suberin deposition in the root, and was more susceptible to drought stress. Interestingly, genetic and biochemical analyses revealed that OsCYP86A9 expression was regulated in the root by certain MYB transcription factors other than OsMYB80. Moreover, mutations in the MYB genes that regulate OsCYP86A9 expression in the root did not impair the male fertility of the plant. Taken together, these findings revealed the critical roles of OsCYP86A9 in plant development and proposed that OsCYP86A9 functions in anther development and root suberin formation via two distinct tissue-specific regulatory pathways.

Design and sequential jumping experimental validation of a musculoskeletal bipedal robot based on the spring-loaded inverted pendulum model.

To effectively control a robot's motion, it is common to employ a simplified model that approximates the robot's dynamics. Nevertheless, discrepancies between the actual mechanical properties of the robot and the simplified model can result in motion failures. To address this issue, this study introduces a pneumatic-driven bipedal musculoskeletal robot designed to closely match the mechanical characteristics of a simplified spring-loaded inverted pendulum (SLIP) model. The SLIP model is widely utilized in robotics due to its passive stability and dynamic properties resembling human walking patterns. A musculoskeletal bipedal robot was designed and manufactured to concentrate its center of mass within a compact body around the hip joint, featuring low leg inertia in accordance with SLIP model principles. Furthermore, we validated that the robot exhibits similar dynamic characteristics to the SLIP model through a sequential jumping experiment and by comparing its performance to SLIP model simulation.

Comparative single-cell analysis reveals heterogeneous immune landscapes in adenocarcinoma of the esophagogastric junction and gastric adenocarcinoma.

Adenocarcinoma of the esophagogastric junction (AEG) is a type of tumor that arises at the anatomical junction of the esophagus and stomach. Although AEG is commonly classified as a subtype of gastric adenocarcinoma (GAC), the tumor microenvironment (TME) of AEG remains poorly understood. To address this issue, we conducted single-cell RNA sequencing (scRNA-seq) on tumor and adjacent normal tissues from four AEG patients and performed integrated analysis with publicly available GAC single-cell datasets. Our study for the first time comprehensively deciphered the TME landscape of AEG, where heterogeneous AEG malignant cells were identified with diverse biological functions and intrinsic malignant nature. We also depicted transcriptional signatures and T cell receptor (TCR) repertoires for T cell subclusters, revealing enhanced exhaustion and reduced clone expansion along the developmental trajectory of tumor-infiltrating T cells within AEG. Notably, we observed prominent enrichment of tumorigenic cancer-associated fibroblasts (CAFs) in the AEG TME compared to GAC. These CAFs played a critical regulatory role in the intercellular communication network with other cell types in the AEG TME. Furthermore, we identified that the accumulation of CAFs in AEG might be induced by malignant cells through FGF-FGFR axes. Our findings provide a comprehensive depiction of the AEG TME, which underlies potential therapeutic targets for AEG patient treatment.

Single-Cell Analysis Reveals Malignant Cells Reshape the Cellular Landscape and Foster an Immunosuppressive Microenvironment of Extranodal NK/T-Cell Lymphoma.

Extranodal natural killer/T-cell lymphoma (NKTCL) is an aggressive type of lymphoma associated with Epstein-Barr virus (EBV) and characterized by heterogeneous tumor behaviors. To better understand the origins of the heterogeneity, this study utilizes single-cell RNA sequencing (scRNA-seq) analysis to profile the tumor microenvironment (TME) of NKTCL at the single-cell level. Together with in vitro and in vivo models, the study identifies a subset of LMP1+ malignant NK cells contributing to the tumorigenesis and development of heterogeneous malignant cells in NKTCL. Furthermore, malignant NK cells interact with various immunocytes via chemokines and their receptors, secrete substantial DPP4 that impairs the chemotaxis of immunocytes and regulates their infiltration. They also exhibit an immunosuppressive effect on T cells, which is further boosted by LMP1. Moreover, high transcription of EBV-encoded genes and low infiltration of tumor-associated macrophages (TAMs) are favorable prognostic indicators for NKTCL in multiple patient cohorts. This study for the first time deciphers the heterogeneous composition of NKTCL TME at single-cell resolution, highlighting the crucial role of malignant NK cells with EBV-encoded LMP1 in reshaping the cellular landscape and fostering an immunosuppressive microenvironment. These findings provide insights into understanding the pathogenic mechanisms of NKTCL and developing novel therapeutic strategies against NKTCL.

Public Attitudes About the Use of Gene Therapy in Mainland China.

Importance: In addition to technical barriers, public attitudes about the use of gene therapy have an important association with the clinical implementation of gene therapy. Objective: To investigate the factors associated with public acceptance of gene therapy among individuals in China. Design, Setting, and Participants: This cross-sectional study used data from a survey conducted among 21 880 individuals in mainland China from June 20 to August 31, 2022. Main Outcomes and Measures: Stepwise linear regression was used to analyze factors associated with public acceptance of gene therapy in 5 key areas: basic personal information (gender, region, age, and educational level), family situation (marital status, children, and cousins), economic status (assets, debts, and insurance coverage), health knowledge (health literacy score and media use), and physical health status (chronic illness, cancer, European Quality of Life 5-Dimension 5-Level version [EQ-5D-5L] score, and Brief Illness Perception Questionnaire [BIPQ] score). Acceptance scores were calculated based on a visual analog scale (range, 0-100, with higher scores indicating higher acceptance of gene therapy). Further subgroup analysis was carried out in different age subgroups and populations with or without chronic diseases. Results: A total of 21 880 participants (mean [SD] age, 39.4 [18.9] years; 10 947 female participants [50.0%]; 10 933 male participants [50.0%]) were analyzed in this study. The mean (SD) acceptance score of gene therapy in the survey was 60.56 (27.60). Compared with people aged 60 years or older, those aged 12 to 18 years had higher acceptance of gene therapy (ß = 1.48 [95% CI, 0.09-2.88]), while groups aged 19 to 30 years (ß = -3.43 [95% CI, -4.80 to -2.07]), 31 to 44 years (ß = -1.44 [95% CI, -2.76 to -0.12]), and 45 to 59 years (ß = -2.05 [95% CI, -3.27 to -0.83]) had lower acceptance. Compared with people living in Eastern China, those in Central China had lower acceptance of gene therapy (ß = -1.58 [95% CI, -2.54 to -0.62]), while those in Western China had higher acceptance (ß = 0.92 [95% CI, 0.09-1.76]). Higher educational level (undergraduate or above vs junior high or below) was associated with higher acceptance of gene therapy (ß = 1.56 [95% CI, 0.49-2.63]). Number of properties owned was also associated with higher acceptance of gene therapy (2 vs 0: ß = 2.38 [95% CI, 1.04-3.72]; ≥3 vs 0: ß = 4.66 [95% CI, 2.92-6.39]). Diagnosis of chronic disease was associated with lower acceptance of gene therapy (ß = -17.86 [95% CI, -20.49 to -15.24]), while diagnosis of cancer was associated with higher acceptance (ß = 6.99 [95% CI, 1.84-12.14]). Higher BIPQ score (ß = 0.40 [95% CI, 0.34-0.45]), higher health literacy score (ß = 0.70 [95% CI, 0.62-0.78]), and media use (ß = 0.49 [95% CI, 0.41-0.57]) were all associated with high acceptance of gene therapy, while a higher EQ-5D-5L score was associated with lower acceptance (ß = -0.29 [95% CI, -0.47 to -0.11]). For older people, being in debt, not having health insurance, and the EQ-5D-5L score were uniquely relevant factors. For people with chronic disease, having an undergraduate degree or higher, a diagnosis of cancer, and the BIPQ score were uniquely relevant factors. Conclusions and Relevance: These results suggest that basic personal information, economic status, health knowledge, and physical health status were the main factors associated with the acceptance of gene therapy. Improving the health literacy of the population and promoting trust in gene therapy may be effective ways to increase the acceptance of gene therapy. Poorer economic levels and worse disease states may reduce the public's willingness to accept gene therapy.

Fusarium Mycotoxins and OTA in Beer from Shanghai, the Largest Megacity in China: Occurrence and Dietary Risk Assessment.

Beer is susceptible to mycotoxin contamination originating from infected grains. It could be that mycotoxins are not completely removed during the brewing process and remain in the final product. Nevertheless, there have been no surveys of exposure to mycotoxin for Chinese inhabitants through beer consumption. This study aimed to investigate the presence of eight mycotoxins in 158 beer samples purchased in Shanghai, the largest megacity in China. The multiple mycotoxins determination was carried out using ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Our findings revealed that 48.1% (76/158) of the beer samples were contaminated with Fusarium toxins. Deoxynivalenol-3-glucoside (D3G) and zearalenone (ZEN) were detected in 34.81% and 16.46% of the total samples, respectively. The significant differences between D3G/ZEN contamination and various beer types were performed. Furthermore, this study performed a health risk assessment for Shanghai residents based on data for Fusarium toxins and ochratoxin A (OTA) present in beer for the first time. The results revealed that the 95th percentile dietary exposures of Shanghai residents did not pose any chronic or acute health risks, either individually or in combination. Dietary exposures to Fusarium toxins revealed different risk levels among residents. The cumulative health risk for women is higher than that for men at the same beer consumption. In addition, the acute risk of DONs exposure for adults deserves concern. The insights obtained from this study may be of assistance for beer manufacturers and governmental regulators to further develop beer monitoring and guarantee public health.

SRSF3/AMOTL1 splicing axis promotes the tumorigenesis of nasopharyngeal carcinoma through regulating the nucleus translocation of YAP1.

Dysregulation of serine/arginine splicing factors (SRSFs) and abnormal alternative splicing (AS) have been widely implicated in various cancers but scarcely investigated in nasopharyngeal carcinoma (NPC). Here we examine the expression of 12 classical SRSFs between 87 NPC and 10 control samples, revealing a significant upregulation of SRSF3 and its association with worse prognosis in NPC. Functional assays demonstrate that SRSF3 exerts an oncogenic function in NPC progression. Transcriptome analysis reveals 1,934 SRSF3-regulated AS events in genes related to cell cycle and mRNA metabolism. Among these events, we verify the generation of a long isoform of AMOTL1 (AMOTL1-L) through a direct bond of the SRSF3 RRM domain with the exon 12 of AMOTL1 to promote exon inclusion. Functional studies also reveal that AMOTL1-L promotes the proliferation and migration of NPC cells, while AMOTL1-S does not. Furthermore, overexpression of AMOTL1-L, but not -S, significantly rescues the inhibitory effects of SRSF3 knockdown. Additionally, compared with AMOTL1-S, AMOTL1-L has a localization preference in the intracellular than the cell membrane, leading to a more robust interaction with YAP1 to promote nucleus translocation. Our findings identify SRSF3/AMOTL1 as a novel alternative splicing axis with pivotal roles in NPC development, which could serve as promising prognostic biomarkers and therapeutic targets for NPC.

DMC (2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone) enhances exercise tolerance via the AMPK-SIRT1-PGC-1α pathway in mice fed a high-fat diet.

Obesity is caused by an imbalance between energy intake and energy expenditure. This study aimed to determine the effects and mechanisms of 2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone (DMC) on exercise tolerance in high-fat diet (HFD)-fed mice. Male C57BL/6J mice were randomly divided into two categories (7 groups [n = 8]): sedentary (control [CON], HFD, 200 mg/kg DMC, and 500 mg/kg DMC) and swimming (HFD, 200 mg/kg DMC, and 500 mg/kg DMC). Except the CON group, all other groups were fed HFD with or without DMC intervention for 33 days. The swimming groups were subjected to exhaustive swimming (three sessions/week). Changes in swimming time, glucolipid metabolism, body composition, biochemical indicators, histopathology, inflammation, metabolic mediators, and protein expression were assessed. DMC combined with regular exercise improved endurance performance, body composition, glucose and insulin tolerance, lipid profile, and the inflammatory state in a dose-dependent manner. Further, DMC alone or combined with exercise could restore normal tissue morphology, reduce fatigue-associated markers, and boost whole-body metabolism and the protein expression of phospho-AMP-activated protein kinase alpha/total-AMP-activated protein kinase alpha (AMPK), sirtuin-1 (SIRT1), peroxisome-proliferator-activated receptor gamma coactivator 1alpha (PGC-1α), and peroxisome proliferator-activated receptor alpha in the muscle and adipose tissues of HFD-fed mice. DMC exhibits antifatigue effects by regulating glucolipid catabolism, inflammation, and energy homeostasis. Furthermore, DMC exerts a synergistic exercise-related metabolic effect via the AMPK-SIRT1-PGC-1α signaling pathway, suggesting that DMC is a potential natural sports supplement with mimicked or augmented exercise effects for obesity prevention.

Ornithine δ-aminotransferase OsOAT is critical for male fertility and cold tolerance during rice plant development.

Cold stress is a major factor limiting the production and geographical distribution of rice (Oryza sativa) varieties. However, the molecular mechanisms underlying cold tolerance remain to be elucidated. Here, we report that ornithine δ-aminotransferase (OsOAT) contributes to cold tolerance during the vegetative and reproductive development of rice. osoat mutant was identified as a temperature-sensitive male sterile mutant with deformed floral organs and seedlings sensitive to cold stress. Comparative transcriptome analysis showed that OsOAT mutation and cold treatment of the wild-type plant led to similar changes in the global gene expression profiles in anthers. OsOAT genes in indica rice Huanghuazhan (HHZ) and japonica rice Wuyungeng (WYG) are different in gene structure and response to cold. OsOAT is cold-inducible in WYG but cold-irresponsive in HHZ. Further studies showed that indica varieties carry both WYG-type and HHZ-type OsOAT, whereas japonica varieties mostly carry WYG-type OsOAT. Cultivars carrying HHZ-type OsOAT are mainly distributed in low-latitude regions, whereas varieties carrying WYG-type OsOAT are distributed in both low- and high-latitude regions. Moreover, indica varieties carrying WYG-type OsOAT generally have higher seed-setting rates than those carrying HHZ-type OsOAT under cold stress at reproductive stage, highlighting the favorable selection for WYG-type OsOAT during domestication and breeding to cope with low temperatures.

Fertility intention and its affecting factors in China: A national cross-sectional survey.

Introduction: Low fertility rate has become an inevitable problem globally. Although current policies have a certain effect on promoting fertility and raising the birth rate, the overall effect is not obvious to meet the need. Therefore, the exploration of fertility intention and its affecting factors is extremely significant. Methods: This study collected demographic data and the intention of respondents to have a second children, which focused on the factors that could affect fertility issues. 11,031 respondents were divided into non-fertile group (n = 5062) and fertile group (n = 5969) according to whether they had children or not, and the fertility group (n = 5969) were divided into group with 1-2 children (n = 5293) and group with ≥3 children (n = 676) according to the number of children. Non-fertility respondents aged 26-40 (n = 1369) were divided to explore the factors affecting the second-children intention. Binary logistic regression analysis was used to determine the affecting factors. Results: It was revealed that gender [Male: OR: 0.60, 95% CI: 0.54-0.68], age [26-40: OR: 16.0, 95% CI: 13.4-19.1; 41-60: OR: 233.8, 95% CI: 186.7-292.6; >60: OR: 105.6, 95% CI: 77.1-144.6], political status [Partisans: OR: 0.48, 95% CI: 0.42-0.54], highest educational level [Middle school: OR: 0.21, 95% CI: 0.17-0.26; College degree or above: OR: 0.09, 95% CI: 0.08-0.11], whether having chronic disease [Yes: OR: 1.95, 95% CI: 1.60-2.38] and depression [Mild depression: OR: 0.63, 95% CI: 0.56-0.72; Moderate depression: OR: 0.43, 95% CI: 0.36-0.53; Moderate to severe depression: OR: 0.45, 95% CI: 0.35-0.57; Severe depression: OR: 0.50, 95% CI: 0.33-0.74] were important factors affecting fertility intention. We found that age [26-40: OR: 0.11, 95% CI: 0.08-0.15; 41-60: OR: 0.15, 95% CI: 0.12-0.18; >60: 0.81, 95% CI: 0.66-0.99], region [Central China: OR: 1.49, 95% CI: 1.20-1.86; Western China: OR: 1.75, 95% CI: 1.41-2.18], resident place [Urban: OR: 0.59, 95% CI: 0.49-0.72], per capita monthly household income [6001-12000: OR: 0.63, 95% CI:0.46-0.83; ≥12,000: OR: 1.83, 95% CI: 1.20-2.80], political status [Non-partisans: OR: 0.24, 95% CI: 0.09-0.69], highest educational level [Middle school: OR: 0.36, 95%CI: 0.27-0.46; College degree or above: OR: 0.22, 95% CI: 0.17-0.30] and anxiety [Moderate anxiety: OR: 1.39, 95% CI: 1.04-1.88; Severe anxiety: OR: 2.19, 95% CI: 1.26-3.80] were the main affecting factors for choosing the number of children. Furthermore, the second-children intention investigation in respondents aged 26-40 showed that gender [Male: OR: 2.06, 95% CI: 1.67-2.53], resident place [Urban: OR: 0.59, 95% CI: 0.49-0.72], per capita monthly household income [≥12,000: OR: 1.86, 95% CI: 1.23-2.82] and pressure [Severe pressure: OR: 0.54, 95% CI: 0.34-0.85] were the important factors. Conclusion: Region, educational level, psychological factors, income, political status and medical insurance were the important factors affecting the intention of fertility and the number of children. The government should take these factors into account when optimizing the existing policy.

Factors affecting acceptance of organ donation in mainland China: A national cross-sectional study.

AIMS AND OBJECTIVES: To explore the acceptances and associated influences of organ donation in mainland China. BACKGROUND: The shortage of organ donors has limited the development of organ transplantation in China. It is important to recognise the target population who has high intention to donate their organs may change the status. DESIGN: We conducted a cross-sectional, multi-stage sampling study collected demographic data and individuals' willingness to accept organ donation. METHODS: A stepwise linear regression analysis was adopted to evaluate the factors related to the attitudes toward organ donation. RESULTS: We collected 11,031 valid samples for the survey. The willingness to donate organs among Chinese residents averaged 56.93 points. To be specific, males (ß = -.03), religious believers (ß = -.01) and parents with a different number of children (all: ß = -.04) are less willing to donate their organs. Respondents who live in an urban area (ß = .03), have higher education level (High school or junior college ß = .04, Bachelor degree or above ß = .09), feel anxious (mild, moderate ß = .02), feel pressured (moderate, severe ß = .08), have higher scores of the Short-Form Health Literacy Instrument (HLS-SF12) (ß = .31), The Self-Management Scale (SHMS) (ß = .16), EuroQol Five Dimensions Questionnaire (EQ-5D) (ß = .04) and EuroQol Visual Analogue Scale (EQ-VAS) (ß = .24), are more positive to donate. CONCLUSIONS: This study firstly discusses the public acceptance of organ donation through a nationwide sample around China. In this study, we discovered that Chinese residents' acceptance level of organ donation and that gender, house, anxiety, pressure, social support and health literacy were the main influencing factors on residents' attitudes. RELEVANCE TO CLINICAL PRACTICE: To figure out the Chinese public acceptance and its influencing factors of organ donation can help nurse transplant coordinators to recognise the target population and the obstacles of organ donation. PATIENT OR PUBLIC CONTRIBUTION: At the phase of collecting data, participants were recruited to fill the questionnaires.

What are the acceptances and associated influences of hospice care in Mainland China? A national cross-sectional study.

Background: China ranks 53rd out of 81 countries in the Quality of Death Index for 2021. Although hospice care demand is increasing, the progress remains slow. It is of great significance to explore the acceptances and associated influencing factors of hospice care. Methods: A cross-sectional survey by quota sampling was conducted in China from July 10th to September 15th, 2021. We collected demographic data and hospice care acceptance. A stepwise linear regression analysis was used. Results: This survey contained 11,031 valid questionnaire results to investigate the hospice care acceptance. It was found that individuals with undergraduate or above (ß = 0.04), more properties [2 (ß = 0.02), 3 (ß = 0.01)], and higher reimbursement types of medical insurance [employee health insurance and commercial health (ß = 0.03), government insurance (ß = 0.04)] had higher hospice acceptance willingness, while males (ß = -0.02) were less willing to accept than females. Psychological conditions [mild anxiety (ß = 0.03), moderate anxiety (ß = 0.01), moderate stress (ß = 0.05), and severe stress (ß = 0.06)] also played an important role. The Self-Management Scale (SHMS) (ß = 0.12), EuroQol Five Dimensions Questionnaire (EQ-5D) (ß = 0.05), EuroQol Visual Analog Scale (EQ-VAS) (ß = 0.21), Short-Form Family Health Scale (FHS-SF) (ß = 0.12), higher scores of the Short-Form Health Literacy Instrument (HLS-SF12) (ß = 0.16), and Perceived Social Support Scale (PSSS) (ß = 0.10) also contributed. Gender subgroup showed that in the male group, age, highest educational level, marital status, number of properties, whether having children, psychological conditions, the SHMS, EQ-5D, EQ-VAS, HLS-SF12, and PSSS showed significant difference. Urban and rural subgroups showed that age, highest educational level, number of properties, whether having chronic disease or psychological conditions, the SHMS, EQ-VAS, HLS-SF12, and PSSS were contributing factors in rural areas. Conclusion: The average score of acceptance of hospice care was 65.02 points. Gender, house, anxiety, pressure, social support, and health literacy were the main influencing factors on residents' attitudes.

The nuclear-encoded plastid ribosomal protein L18s are essential for plant development.

Plastid ribosomal proteins (PRPs) are necessary components for plastid ribosome biogenesis, playing essential roles in plastid development. The ribosomal protein L18 involved in the assemble of 5S rRNA and 23S rRNA, is vital for E. coli viability, but the functions of its homologs in plant plastid remain elusive. Here, we characterized the functions of the plant plastid ribosomal protein L18s (PRPL18s) in Arabidopsis and rice. AtPRPL18 was ubiquitously expressed in most of the plant tissues, but with higher expression levels in seedling shoots, leaves, and flowers. AtPRPL18 was localized in chloroplast. Genetic and cytological analyses revealed that a loss of function of AtPRPL18 resulted in embryo development arrest at globular stage. However, overexpression of AtPRPL18 did not show any visible phenotypical changes in Arabidopsis. The rice OsPRPL18 was localized in chloroplast. In contrast to AtPRPL18, knockout of OsPRPL18 did not affect embryo development, but led to an albino lethal phenotype at the seedling stage. Cytological analyses showed that chloroplast development was impaired in the osprpl18-1 mutant. Moreover, a loss-function of OsPRPL18 led to defects in plastid ribosome biogenesis and a serious reduction in the efficiency of plastid intron splicing. In all, these results suggested that PRPL18s play critical roles in plastid ribosome biogenesis, plastid intron splicing, and chloroplast development, and are essential for plant survival.

Icariside II Exerts Anti-Type 2 Diabetic Effect by Targeting PPARα/γ: Involvement of ROS/NF-κB/IRS1 Signaling Pathway.

Type 2 diabetes mellitus (T2DM) is a multisystem and complex metabolic disorder which is associated with insulin resistance and impairments of pancreatic ß-cells. Previous studies have shown that icariside II (ICS II), one of the main active ingredients of Herba Epimedii, exerts potent anti-inflammatory and anti-oxidative properties. In this study, we investigated whether ICS II exerted anti-T2DM profile and further explored its possible underlying mechanism both in vivo and in vitro. db/db mice were administered ICS II (10, 20, 40 mg·kg-1) for 7 weeks. We found that ICS II dose-dependently attenuated hyperglycemia and dyslipidemia, as well as inhibited hepatic steatosis and islet architecture damage in db/db mice. Moreover, ICS II not only dramatically reduced inflammatory cytokines and oxidative stress, but also up-regulated PPARα/γ protein expressions, phosphorylation of Akt, GSK3ß and IR, meanwhile, down-regulated phosphorylation of NF-κB(p65) and IRS1 in db/db mice. In palmitic acid (PA)-treated HepG2 or MIN6 cells, ICS II (5-20 µM) concentration-dependently promoted the cell viability via mediating PPARα/γ/NF-κB signaling pathway. PPARα/γ knockout by CRISPR-Cas9 system partly abolished the protective effects of ICS II on HepG2 or MIN6 cells following PA insults. These findings reveal that ICS II effectively confer anti-T2DM property by targeting PPARα/γ through mediation of ROS/NF-κB/IRS1 signaling pathway.

Icariside II, a Naturally Occurring SIRT3 Agonist, Protects against Myocardial Infarction through the AMPK/PGC-1α/Apoptosis Signaling Pathway.

Myocardial infarction (MI) refers to the death of cardiomyocytes triggered by a lack of energy due to myocardial ischemia and hypoxia, and silent mating type information regulation 2 homolog 3 (SIRT3) plays an essential role in protecting against myocardial oxidative stress and apoptosis, which are deemed to be the principal causes of MI. Icariside II (ICS II), one of the main active ingredients of Herbal Epimedii, possesses extensive pharmacological activities. However, whether ICS II can protect against MI is still unknown. Therefore, this study was designed to investigate the effect and possible underlying mechanism of ICS II on MI both in vivo and in vitro. The results showed that pretreatment with ICS II not only dramatically mitigated MI-induced myocardial damage in mice but also alleviated H9c2 cardiomyocyte injury elicited by oxygen and glucose deprivation (OGD), which were achieved by suppressing mitochondrial oxidative stress and apoptosis. Furthermore, ICS II elevated the phosphorylation level of adenosine monophosphate-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1α) expression, thereby activating SIRT3. However, these protective effects of ICS II on MI injury were largely abolished in SIRT3-deficient mice, manifesting that ICS II-mediated cardioprotective effects are, at least partly, due to the presence of SIRT3. Most interestingly, ICS II directly bound with SIRT3, as reflected by molecular docking, which indicated that SIRT3 might be a promising therapeutic target for ICS II-elicited cardioprotection in MI. In conclusion, our findings illustrate that ICS II protects against MI-induced oxidative injury and apoptosis by targeting SIRT3 through regulating the AMPK/PGC-1α pathway.

Icariside II Restores Vascular Smooth Muscle Cell Contractile Phenotype by Enhancing the Focal Adhesion Signaling Pathway in the Rat Vascular Remodeling Model.

Vascular smooth muscle cell (VSMC) phenotypic transition represents the fundamental pathophysiological alteration in the vascular remodeling process during the initiation and progression of cardiovascular diseases. Recent studies have revealed that Icariside II (ICS-II), a flavonol glycoside derived from the traditional Chinese medicine Herba Epimedii, exhibited therapeutic effects in various cardiovascular diseases. However, the therapeutic efficacy and underlying mechanisms of ICS-II regarding VSMC phenotypic transition were unknown. In this study, we investigated the therapeutic effects of ICS-Ⅱ on vascular remodeling with a rat's balloon injury model in vivo. The label-free proteomic analysis was further implemented to identify the differentially expressed proteins (DEPs) after ICS-II intervention. Gene ontology and the pathway enrichment analysis were performed based on DEPs. Moreover, platelet-derived growth factor (PDGF-BB)-induced primary rat VSMC was implemented to verify the restoration effects of ICS-II on the VSMC contractile phenotype. Results showed that ICS-II could effectively attenuate the vascular remodeling process, promote SMA-α protein expression, and inhibit OPN expression in vivo. The proteomic analysis identified 145 differentially expressed proteins after ICS-II intervention. Further, the bioinformatics analysis indicated that the focal adhesion signaling pathway was enriched in the ICS-II group. In vitro studies showed that ICS-II suppressed VSMC proliferation and migration, and promoted VSMC contractile phenotype by modulating the focal adhesion signaling pathway. Taken together, our results suggest that ICS-II attenuates the vascular remodeling process and restores the VSMC contractile phenotype by promoting the focal adhesion pathway.

Genome-wide identification and expression profiling analysis of sucrose synthase (SUS) and sucrose phosphate synthase (SPS) genes family in Actinidia chinensis and A. eriantha.

Sucrose synthase (SUS) is a common sugar-base transfer enzyme in plants, and sucrose phosphate synthase (SPS) is one of the major enzymes in higher plants that regulates sucrose synthesis. However, information of the SPS and SUS gene families in Actinidia, as well as their evolutionary and functional properties, is limited. According to the SPS and SUS proteins conserved domain of Arabidopsis thaliana, we found 6 SPS genes and 6 SUS genes from A. chinensis (cultivar: 'Hongyang'), and 3 SPS genes and 6 SUS genes from A. eriantha (cultivar: 'White'). The novel CDC50 conserved domains were discovered on AcSUS2, and all members of the gene family contain similar distinctive conserved domains. The majority of SUS and SPS proteins were hydrophilic, lipid-soluble enzymes that were expected to be found in the cytoplasm. The tertiary structure of SPS and SUS protein indicated that there were many tertiary structures in SPS, and there were windmill-type and spider-type tertiary structures in SUS. The phylogenetic tree was created using the neighbor-joining method, and members of the SPS and SUS gene families are grouped into three subgroups. Genes with comparable intron counts, conserved motifs, and phosphorylation sites were clustered together first. SPS and SUS were formed through replication among their own family members. AcSPS1, AcSPS2, AcSPS4, AcSPS5, AcSUS5, AcSUS6, AeSPS3, AeSUS3 and AeSUS4 were the important genes in regulating the synthesis and accumulation of sucrose for Actinidia during the fruit growth stages.

Mulberry Leaf Extract Alleviates Staphylococcus aureus-Induced Conjunctivitis in Rabbits via Downregulation of NLRP3 Inflammasome and Upregulation of the Nrf2 System and Suppression of Pro-Inflammatory Cytokines.

INTRODUCTION: Mulberry (Morus alba L.) leaves are widely used in traditional Chinese medicine for their antioxidant, anti-inflammatory, antibacterial, anti-obesity, antidiabetic, antiatherosclerotic, and anticancer properties. The current study aimed to investigate the effect of mulberry leaf extract (MLE) on Staphylococcus aureus (S. aureus)-induced conjunctivitis (5 × 109 colony-forming units, 0.5 mL/eye) in a rabbit model. METHODS: Rabbits were treated with MLE (5 mL/kg·d-1 and 10 mL/kg·d-1), 0.9% saline, pearl bright eye (PBE) drops, or erythromycin eye ointment (EEO) group for 5 days. The ocular infection symptoms, bacterial negative conversion rate, and conjunctival histopathological changes of rabbits in each group were observed. The expression of caspase-1, apoptosis-associated speck-like protein containing a caspase recruitment domain, NOD-like receptor leucine-rich pyrin domain-containing protein 3 (NLRP3), interleukin (IL)-18, IL-6, IL-1ß, TNFα, Keap1, and nuclear factor erythroid 2-related factor 2 (Nrf2) in conjunctival tissue of rabbits were detected by quantitative real-time reverse transcription PCR and/or Western blot analysis. RESULTS: The results showed that MLE treatment significantly reduced the clinical sign scores of conjunctivitis, alleviated clinical signs, and decreased bacterial load, and histological damage in a time- and dose-dependent manner was compared to that in the control group. The antibacterial and anti-inflammatory activities of MLE (10 mL/kg·d-1) were similar to those of the positive control drug PBE and EEO. In addition, MLE significantly decreased the levels of pro-inflammatory cytokines, downregulated the NLRP3 inflammasome, and upregulated the Nrf2 system. CONCLUSIONS: MLE is effective in alleviating S. aureus-induced conjunctivitis in rabbits, and this mechanism is associated with the inhibition of the NLRP3 inflammasome and activation of the Nrf2 system to regulate pro-inflammatory signaling.

Icariside II Attenuates Vascular Remodeling Via Wnt7b/CCND1 Axis.

ABSTRACT: Angioplasty often fails due to the abnormal proliferation of vascular smooth muscle cells (VSMCs). Success rates of angioplasty may increase following the administration of an agent that effectively ameliorates aberrant vascular remodeling. Icariside II (ICS-II) is a natural flavonol glycoside extract from the Chinese herbal medicine Epimedii that possesses several medicinal qualities that are beneficial in humans. Nevertheless, the role of ICS-II in addressing aberrant vascular remodeling have yet to be clarified. The current investigation studies the molecular effects of ICS-Ⅱ on balloon-inflicted neointimal hyperplasia in rats in vivo and on platelet-derived growth factor-induced vascular proliferation in primary rat aortic smooth muscle cells (VSMCs) in vitro. ICS-II was found to be as effective as rapamycin, the positive control used in this study. ICS-II inhibited neointimal formation in injured rat carotid arteries and notably reduced the expression of Wnt7b. ICS-Ⅱ significantly counteracted platelet-derived growth factor-induced VSMCs proliferation. Cell cycle analysis showed that ICS-II triggered cell cycle arrest during the G1/S transition. Western blot analysis further indicated that this cell cycle arrest was likely through Wnt7b suppression that led to CCND1 inhibition. In conclusion, our findings demonstrate that ICS-II possesses significant antiproliferative qualities that counteracts aberrant vascular neointimal hyperplasia. This phenomenon most likely occurs due to the suppression of the Wnt7b/CCND1 axis.

Updated evidence of Dengzhan Shengmai capsule against ischemic stroke: A systematic review and meta-analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Ischemic stroke is the most common type of stroke, with high mortality, disability and recurrence rate, which brings a heavy burden to individuals, families and the medical system. Therefore, the intervention and treatment of ischemic stroke are of great significance. Chinese herbal medicine is widely used in treating stroke, for example, Dengzhan shengmai (DZSM) capsule. The current systematic review aims to comprehensively evaluate the efficacy and safety of the DZSM capsule in treating ischemic stroke. MATERIALS AND METHODS: Eligible randomized controlled trials (RCTs) were included to evaluate the efficacy and safety of Chinese herbal medicine DZSM capsule in treating ischemic stroke. Eight electronic databases were searched up to January 27, 2021. The risk ratio (RR), standardized mean difference (SMD), or weighted mean difference (WMD) with 95% confidence interval (CI) were used to assess DZSM capsule treatment outcomes. RESULTS: A total of 28 RCTs involving 6683 participants were included in the systematic review and meta-analysis. Compared with conventional therapy group, DZSM capsule plus conventional therapy improved Barthel Index scores (WMD: 8.97, 95%CI: 5.88-12.05) and reduced modified Rankin Scale (WMD: -0.75, 95%CI: -1.02∼ -0.48), reduced neurological functional deficit scores (WMD: -2.81, 95%CI: -4.17∼ -1.44), recurrence rate (RR: 0.57, 95%CI: 0.44-0.73) and mortality (RR: 0.54, 95%CI: 0.31-0.95), improved clinical effect (RR: 1.18, 95%CI: 1.12-1.24) and quality of life (WMD: 21.67, 95%CI: 6.74-36.61), exhibited a beneficial effect on hemorheology such as elevated levels of APTT (SMD: 1.17, 95%CI: 0.87-1.47) and INR (SMD: 1.12, 95%CI: 0.82-1.42), and on lipid metabolism such as levels of TC (SMD: -0.62, 95%CI: -1.04 âˆ¼ -0.20), TG (SMD: -0.72, 95%CI: -1.18∼ -0.26), LDL (SMD: -1.14, 95%CI: -1.57∼ -0.71) and HDL (SMD: 0.93, 95%CI: 0.36-1.50). No trials reported severe adverse events. CONCLUSION: DZSM capsule appears to be safe and effective in clinical applications for ischemic stroke. Based on conventional therapy, adding the DZSM capsule could reduce the mortality, recurrence rate, and neurological functional deficit scores, improve clinical effect and quality of life. In addition, compared with conventional therapy, the addition of the DZSM capsule played a beneficial role in hemorheology and lipid metabolism, which may attribute to the potential mechanism.