The plastid-localized lipoamide dehydrogenase 1 is crucial for redox homeostasis, tolerance to arsenic stress and fatty acid biosynthesis in rice.

Soil contamination with arsenic (As) can cause phytotoxicity and reduce crop yield. The mechanisms of As toxicity and tolerance are not fully understood. In this study, we used a forward genetics approach to isolate a rice mutant, ahs1, that exhibits hypersensitivity to both arsenate and arsenite. Through genomic resequencing and complementation tests, we identified OsLPD1 as the causal gene, which encodes a putative lipoamide dehydrogenase. OsLPD1 was expressed in the outer cell layer of roots, root meristem cells, and in the mesophyll and vascular tissues of leaves. Subcellular localization and immunoblot analysis demonstrated that OsLPD1 is localized in the stroma of plastids. In vitro assays showed that OsLPD1 exhibited lipoamide dehydrogenase (LPD) activity, which was strongly inhibited by arsenite, but not by arsenate. The ahs1 and OsLPD1 knockout mutants exhibited significantly reduced NADH/NAD+ and GSH/GSSG ratios, along with increased levels of reactive oxygen species and greater oxidative stress in the roots compared with wild-type (WT) plants under As treatment. Additionally, loss-of-function of OsLPD1 also resulted in decreased fatty acid concentrations in rice grain. Taken together, our finding reveals that OsLPD1 plays an important role for maintaining redox homeostasis, conferring tolerance to arsenic stress, and regulating fatty acid biosynthesis in rice.

Gastrodin alleviates mitochondrial dysfunction by regulating SIRT3-mediated TFAM acetylation in vascular dementia.

BACKGROUND: Mitochondrial dysfunction is key to the pathogenesis of vascular dementia (VaD). Sirtuin-3 (SIRT3), an essential member of the sirtuins family, has been proven to be a critical sirtuin in regulating mitochondrial function. The phenolic glucoside gastrodin (GAS), a bioactive ingredient from Gastrodiae Rhizome (known in Chinese as Tian ma) demonstrates significant neuroprotective properties against central nervous system disorders; however, the precise mechanisms through which GAS modulates VaD remain elusive. PURPOSE: This study aims to investigate whether GAS confers a protective role against VaD, and to figure out the underlying molecular mechanisms. METHODS: A bilateral common carotid artery occlusion (BCCAO)-mediated chronic cerebral hypoperfusion (CCH) VaD rat model and a hypoxia model using HT22 cells were employed to investigate pharmacological properties of GAS in mitigating mitochondrial dysfunction. A SIRT3 agonist resveratrol (RES), a SIRT3 inhibitor 3-TYP and SIRT3-knockdown in vitro were used to explore the mechanism of GAS in association with SIRT3. The ability of SIRT3 to bind and deacetylate mitochondrial transcription factor A (TFAM) was detected by immunoprecipitation assay, and TFAM acetylation sites were further validated using mass spectrometry. RESULTS: GAS increased SIRT3 expression and ameliorated mitochondrial structure, mitochondrial respiration, mitochondrial dynamics along with upregulated TFAM, mitigating oxidative stress and senescence. Comparable results were noted with the SIRT3 agonist RES, indicating an impactful neuroprotection played by SIRT3. Specifically, the attenuation of SIRT3 expression through knockdown techniques or exposure to the SIRT3 inhibitor 3-TYP in HT22 cells markedly abrogated GAS-mediated mitochondrial rescuing function. Furthermore, our findings elucidate a novel facet: SIRT3 interacted with and deacetylated TFAM at the K5, K7, and K8 sites. Decreased SIRT3 is accompanied by hyper-acetylated TFAM. CONCLUSION: The present results were the first to demonstrate that the SIRT3/TFAM pathway is a protective target for reversing mitochondrial dysfunction in VaD. The findings suggest that GAS-mediated modulation of the SIRT3/TFAM pathway, a novel mechanism, could ameliorate CCH-induced VaD, offering a potentially beneficial therapeutic strategy for VaD.

Factors associated with workplace violence against Chinese healthcare workers: an online cross-sectional survey.

Objectives: Workplace violence (WPV) against healthcare workers (HCWs) has reached significant levels globally, impeding the quality and accessibility of healthcare systems. However, there is limited available knowledge regarding the determinants linked with WPV among HCWs and the discrepancies observed across various levels of hospitals in China. The objective of the present research was to investigate the factors linked to WPV and job satisfaction among HCWs in China. Methods: A self-developed questionnaire based on WeChat was employed to collect data. The questionnaire consisted of demographic information as well as occupational factors. To measure WPV, the Chinese version of the Workplace Violence Scale was utilized. Career satisfaction was assessed through two questions regarding career choices. The collected data was analyzed using descriptive analyses, chi-square tests, and multivariate logistic regressions. Results: A total of 3,781 valid questionnaires (1,029 doctors and 2,752 nurses) were collected. Among all participants, 2,201 (58.2%) reported experiencing at least one form of WPV in the past year, with emotional abuse being the most frequent occurrence (49.7%), followed by threats (27.9%). The multivariate logistic regression analysis revealed several risk factors associated with WPV, including male gender, shift work, senior professional title, bachelor's degree education, employment in secondary-level hospitals, and working over 50 h per week (p < 0.05). Career satisfaction among HCWs who experienced high levels of WPV was low, with only 11.2% remaining confident in their profession, and a mere 2.0% supporting their children pursuing careers in healthcare. Conclusion: WPV poses a significant challenge within the Chinese healthcare system. Efforts should be made to address the identified risk factors and promote a safe and satisfying working environment for HCWs.

Digital health literacy and associated factors among internet users from China: a cross-sectional study.

BACKGROUND: As the internet develops and 5G technology becomes increasingly prominent, the internet has become a major source of health-related information. Increasingly, people use the internet to find health-related information, and digital health literacy is now a set of essential capabilities to improve their health in the digital era. However, little is known about the factors that influencing digital health literacy. This study aimed to assess digital health literacy scores and identify its influencing factors among internet users in China. Additionally, this study explored the participant's actual skills using an additional set of performance-based items from the Digital Health Literacy Instrument (DHLI). METHODS: An online cross-sectional study was conducted in August 2022. Participants aged ≥18 years were recruited to complete the survey. Data were collected using the Chinese revised version of the DHLI, the self-reported internet use questionnaire, and the sociodemographic questionnaire. We conducted multivariate linear regression analyses to explore the relationships among the sociodemographic variables, behavior of internet use, and the digital health literacy scores. RESULTS: In total, 702 participants completed the survey. The mean DHLI score was 2.69 ± 0.61. Multivariate linear regression analyses showed that the age groups 35-49 (ß = - 0.08, P = 0.033), 50-64 (ß = - 0.161, P < 0.001), and ≥ 65 (ß = - 0.138, P < 0.001) were negatively associated with DHL scores. However, education level, including bachelor's or associate degree (ß = 0.255, P = 0.002) and master's degree and above (ß = 0.256, P < 0.001), frequency of health-related Internet usage (ß = 0.192, P < 0.001), the number of digital devices used (ß = 0.129, P = 0.001), and OHISB (ß = 0.103, P = 0.006) showed a positive relationship with DHL scores. CONCLUSIONS: The study findings demonstrate that age, educational levels, number of technological devices used, and greater use of the web for health information were independently associated with DHL scores. Healthcare providers should consider providing training programs tailored to specific sociodemographic factors to improve the ability that find and use accurate information online to meet digital health services, which contributes to enhance their self-management and reduce health disparities.

Efficacy and safety of direct oral anticoagulants versus low-molecular-weight heparin for thromboprophylaxis after cancer surgery: a systematic review and meta-analysis.

BACKGROUND: Direct oral anticoagulants (DOACs) used as an alternative to low-molecular-weight heparin (LMWH) for thromboprophylaxis after cancer surgery for venous thromboembolic events (VTE) remains unclear. This study aimed to investigate the efficacy and safety of DOACs versus LMWH in these patients. MATERIALS AND METHODS: A search of EMBASE, MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science was carried out and included all randomized controlled trials (RCTs) and observational studies that directly compared DOACs with LMWH for thromboprophylaxis in patients after cancer surgery through July 25, 2023. The primary efficacy and safety outcomes were VTE, major bleeding, and clinically relevant non-major bleeding (CRNMB) within 30 days of surgery. The risk of bias was assessed using the Cochrane Risk of Bias 2 (RoB2) tool for RCTs and ROBINS-I tool for non-randomized studies. This study was registered in PROSPERO (CRD42023445386). RESULTS: We retrieved 5149articles, selected 27 for eligibility, and included 10 studies (three RCTs and seven observational studies) encompassing 3054 patients who underwent postoperative thromboprophylaxis with DOACs (41%) or LMWH (59%). Compared to LMWH thromboprophylaxis, DOACs had a comparable risk of VTE (RR:0.69[95% CI:0.46-1.02], I2 = 0%), major bleeding (RR:1.55 [95% CI:0.82-2.93], I2 = 2%), and CRNMB (RR, 0.89 [95% CI, 0.4-1.98], I2 = 31%) during the 30-day postoperative period. Subgroup analysis of VTE and major bleeding suggested no differences according to study type, extended thromboprophylaxis, tumor types, or different types of DOAC. CONCLUSION: DOACs are potentially effective alternatives to LMWH for thromboprophylaxis in patients undergoing cancer surgery, without increasing the risk of major bleeding events.

Investigating the correlation of delirium after cardiac surgery with memories and posttraumatic stress disorder consequences of intensive care unit: A prospective cohort study.

OBJECTIVES: To explore the differences in post-intensive care unit memory and posttraumatic stress disorder symptoms between patients with and without delirium, and assess the correlations between the two. DESIGN: Prospective cohort observation study. SETTING: A cardiac intensive care unit of a tertiary hospital in China. We enrolled 318 consecutive patients after cardiac surgery between December 2017 and March 2019. MAIN OUTCOME MEASURES: Delirium was assessed using the Confusion Assessment Method for the ICU from intensive care unit admission to discharge. Intensive care unit memory was assessed using the ICU-Memory Tool through face-to-face interviews one week after discharge. Posttraumatic stress disorder was measured telephonically using the Impact of Events Scale-revised questionnaire at three months post-discharge. RESULTS: Eighty patients each in the delirium and non-delirium groups were enrolled for follow-up interviews. Patients with delirium had vaguer memories of pre-intensive care unit admission and of their stay, and recollected more memories of feelings (vs. without delirium). Posttraumatic stress disorder was diagnosed in 14 patients with and in seven without delirium, with non-significant differences between groups. Delirium did not influence post-intensive care unit factual, feeling, and delusional memories, nor posttraumatic stress disorder and hyperarousal, intrusion, and avoidance. The memories of feelings were positively correlated with the last three (r = 0.285, r = 0.390 and r = 0.373, respectively). CONCLUSION: Patients with delirium had vague intensive care unit memories. Memories of feelings were positively correlated with symptoms of hyperarousal, intrusion, and avoidance. Delirium did not influence factual, feeling, or delusional memories nor posttraumatic stress disorder incidence and symptoms. IMPLICATIONS FOR CLINICAL PRACTICE: Interventions are needed to reduce the impact of vague memory in patients with post-intensive care unit delirium. Memories of feelings should be focused on because of their correlation with hyperarousal, intrusion, and avoidance. Delirium prevention and early recognition measures are suggested.

Probing the hair detectability of prohibited substances in sports: an in vivo-in silico-clinical approach and analytical implications compared with plasma, urine, and faeces.

Hair analysis is a crucial method in forensic toxicology with potential applications in revealing doping histories in sports. Despite its widespread use, knowledge about detectable substances in hair is limited. This study systematically assessed the detectability of prohibited substances in sports using a multifaceted approach. Initially, an animal model received a subset of 17 model drugs to compare dose dependencies and detection windows across different matrices. Subsequently, hair incorporation data from the animal experiment were extrapolated to all substances on the World Anti-Doping Agency's List through in-silico prediction. The detectability of substances in hair was further validated in a proof-of-concept human study involving the consumption of diuretics and masking agents. Semi-quantitative analysis of substances in specimens was performed using ultra-performance liquid chromatography-tandem mass spectrometry. Results showed plasma had optimal dose dependencies with limited detection windows, while urine, faeces, and hair exhibited a reasonable relationship with the administered dose. Notably, hair displayed the highest detection probability (14 out of 17) for compounds, including anabolic agents, hormones, and diuretics, with beta-2 agonists undetected. Diuretics such as furosemide, canrenone, and hydrochlorothiazide showed the highest hair incorporation. Authentic human hair confirmed diuretic detectability, and their use duration was determined via segmental analysis. Noteworthy is the first-time reporting of canrenone in human hair. Anabolic agents were expected in hair, whereas undetectable compounds, such as peptide hormones and beta-2 agonists, were likely due to large molecular mass or high polarity. This study enhances understanding of hair analysis in doping investigations, providing insights into substance detectability.

Mental health status and related factors influencing healthcare workers during the COVID-19 pandemic: A systematic review and meta-analysis.

BACKGROUND: The mental health of healthcare workers during the coronavirus-2019 pandemic was seriously affected, and the risk of mental health problems was high. The present study sought to systematically evaluate the mental health problems of healthcare workers worldwide during the pandemic and to determine the latest global frequency of COVID-19 associated mental health problems. METHODS: Data in the Cumulative Index to Nursing and Allied Health Literature (CINAHL), EMBASE, Elsevier, MEDLINE, PubMed, PsycINFO and the Web of Science before November 11, 2022, were systematically searched. Cohort, case-control and cross-sectional studies were included. The meta-analysis used a random effects model to synthesize the comprehensive prevalence rate of mental health problems. Subgroup analyses were performed based on time of data collection; whether the country was or was not developed; continent; doctors and nurses; doctors/nurses vs. other healthcare workers; and psychological evaluation scale. RESULTS: A total of 161 studies were included, including 341,014 healthcare workers worldwide, with women accounting for 82.8%. Occupationally, 16.2% of the healthcare workers were doctors, 63.6% were nurses and 13.3% were other medical staff. During the pandemic, 47% (95% confidence interval [CI], 35-60%) of healthcare workers reported job burnout, 38% (95% CI, 35-41%) experienced anxiety, 34% (95% CI 30-38%) reported depression, 30% (95% CI, 29-31%) had acute stress disorder, and 26% (95% CI, 21-31%) had post-traumatic stress disorder. CONCLUSIONS: The study found that there were common mental health problems among health care workers during the COVID-19 pandemic. The most common was job burnout, followed by anxiety, depression, acute stress and post-traumatic stress disorder. Although the global pandemic has been brought under control, its long-term impact on the mental health of healthcare workers cannot be ignored. Additional research is required to develop measures to prevent, monitor and treat psychological disorders among healthcare workers.

Review of research progress on the role of the effective components of traditional Chinese medicine in sepsis with multiple organ dysfunction.

The concept of sepsis has recently evolved from one of a 'systemic inflammatory response syndrome caused by infection' to a 'severe, potentially fatal organic dysfunction caused by an inadequate or imbalanced host response to infection'. Organ dysfunction is closely related to sepsis. Multiple organ dysfunction syndrome (MODS) is the most serious outcome of sepsis, often leading to a poor prognosis. However, specific drugs for sepsis and MODS caused by sepsis remain undetermined, and the fatality rate is relatively high. Under the guidance of modern medicine, traditional Chinese medicine (TCM) has gained a wealth of experience in the prevention and treatment of sepsis and plays a key role via the effects of its numerous components, pathways and targets. This study used 'Sepsis', 'Organ dysfunction' and 'Traditional Chinese medicine' as strategies for searching the databases of Chinese National Knowledge Infrastructure, Wanfang, PubMed and The Web of Science. This paper presents an overview of the current status of TCM component formulations for preventing and treating sepsis with MODS to provide a theoretical basis for clinical treatment and drug development.

Personalised neoantigen-based therapy in colorectal cancer.

Colorectal cancer (CRC) has become one of the most common tumours with high morbidity, mortality and distinctive evolution mechanism. The neoantigens arising from the somatic mutations have become considerable treatment targets in the management of CRC. As cancer-specific aberrant peptides, neoantigens can trigger the robust host immune response and exert anti-tumour effects while minimising the emergence of adverse events commonly associated with alternative therapeutic regimens. In this review, we summarised the mechanism, generation, identification and prognostic significance of neoantigens, as well as therapeutic strategies challenges of neoantigen-based therapy in CRC. The evidence suggests that the establishment of personalised neoantigen-based therapy holds great promise as an effective treatment approach for patients with CRC.

Assessing anti-doping knowledge among Taiwanese pharmacists.

BACKGROUND: Taiwan's unique health behaviour, such as extensive exposure to Chinese Herbal Medicine (CHM), has introduced a risk of inadvertent doping among competing athletes. Pharmacy professionals have an imperative role in advising athletes on the safe use of medicines. This study provides an overview of anti-doping knowledge and educational needs among pharmacists in Taiwan and examines influencing factors. METHODS: A cross-sectional online questionnaire survey consisting of five domains, namely demographic characteristics, source of prohibited substances, identification of prohibited substances, understanding of doping control, and education needs on anti-doping, was distributed to the registered pharmacists in Taiwan. In total, 491 responses were included in the analyses. RESULTS: Respondents (65% female, aged 41.9 ± 11.4 years, with 68% having a Bachelor's degree) reported a moderate anti-doping knowledge score of 37.2 ± 4.9, ranging from 21 to 48 (out of 51). Fifteen per cent of them had the experience of being counselled about drug use in sports. Higher knowledge scores were observed in younger respondents, showing an age-dependent effect (p < 0.001). Individuals practising in southern Taiwan (compared to northern Taiwan) and those working at clinics (compared to hospitals) exhibited lower knowledge. Most of the respondents (90%) knew that stimulant ephedrine is prohibited in sports, but few had recognised diuretic furosemide (38%) and CHM (7%) containing ß2-agonist higenamine. Approximately 90% of respondents agreed with the need for anti-doping education. CONCLUSIONS: This study highlights the heterogeneity of anti-doping knowledge among pharmacy professionals and provides practical relevance in organising future educational topics and research-based activities.

Dextran sulfate sodium-induced gut microbiota dysbiosis aggravates liver injury in mice with S100-induced autoimmune hepatitis.

Recently, the incidence of autoimmune hepatitis (AIH) has gradually increased, and the disease can eventually develop into cirrhosis or even hepatoma if left untreated. AIH patients are often characterized by gut microbiota dysbiosis, but whether gut microbiota dysbiosis contributes to the progression of AIH remains unclear. In this study, we investigate the role of gut microbiota dysbiosis in the occurrence and development of AIH in mice with dextran sulfate sodium salt (DSS) induced colitis. C57BL/6J mice were randomly divided into normal group, S100-induced AIH group, and DSS+S100 group (1 % DSS in the drinking water), and the experimental cycle lasted for four weeks. We demonstrate that DSS administration aggravates hepatic inflammation and disruption of the intestinal barrier, and significantly changes the composition of gut microbiota in S100-induced AIH mice, which are mainly characterized by increased abundance of pathogenic bacteria and decreased abundance of beneficial bacteria. These results suggest that DSS administration aggravates liver injury of S100-induced AIH, which may be due to DSS induced gut microbiota dysbiosis, leading to disruption of the intestinal barrier, and then, the microbiota translocate to the liver, aggravating hepatic inflammation.

Effect of Dietary Gelsemium elegans Benth. Extract on the Growth, Slaughter Performance, Meat Quality, Intestinal Morphology, and Microflora of Yellow-Feathered Chickens.

The plant species Gelsemium elegans Benth. (GEB) promotes pig and sheep growth; however, little is known about its effects in chickens. In this study, a GEB extract (GEBE) was prepared, and its effects on the growth, slaughter, antioxidant performance, meat quality, serum biochemical indices, intestinal morphology, and microflora of yellow-feathered chickens were evaluated. In total, 600 chickens aged 15 days were randomly divided into four groups with five replicates each and fed a basal diet containing 0% (control), 0.25% (0.25 GEBE), 0.75% (0.75 GEBE), or 1.25% (1.25 GEBE) GEBE until 49 days of age. Chickens were then killed, and their meat, organs, and serum and cecal contents were collected. GEBE reduced the feed conversion ratio, particularly in the 0.75 and 1.25 GEBE groups. Furthermore, the GEBE diet improved meat tenderness and reduced the meat expressible moisture content and liver malondialdehyde content, indicating high meat quality. Whereas the 0.25 GEBE diet increased the level of Lactobacillus acidophilus in the cecum, the 0.75 GEBE diet decreased the Escherichia coli level therein. These findings demonstrate that GEBE may improve the meat quality and cecal microbiota of yellow-feathered chickens, providing a basis for identifying candidate alternatives to conventional antibiotics as growth promoting feed additives.

Heparanase inhibition leads to improvement in patients with acute gastrointestinal injuries induced by sepsis.

BACKGROUND: Patients with sepsis are at high risk for acute gastrointestinal injury (AGI), but the diagnosis and treatment of AGI due to sepsis are unsatisfactory. Heparanase (HPA) plays an important role in septic AGI (S-AGI), but its specific mechanism is not completely understood, and few clinical reports are available. AIM: To explore the effect and mechanism of HPA inhibition in S-AGI patients. METHODS: In our prospective clinical trial, 48 patients with S-AGI were randomly assigned to a control group to receive conventional treatment, whereas 47 patients were randomly assigned to an intervention group to receive conventional treatment combined with low molecular weight heparin. AGI grade, sequential organ failure assessment score, acute physiology and chronic health evaluation II score, D-dimer, activated partial thromboplastin time (APTT), anti-Xa factor, interleukin-6, tumour necrosis factor-α, HPA, syndecan-1 (SDC-1), LC3B (autophagy marker), intestinal fatty acid binding protein, D-lactate, motilin, gastrin, CD4/CD8, length of intensive care unit (ICU) stay, length of hospital stay and 28-d survival on the 1st, 3rd and 7th d after treatment were compared. Correlations between HPA and AGI grading as well as LC3B were compared. Receiver operator characteristic (ROC) curves were generated to evaluate the diagnostic value of HPA, intestinal fatty acid binding protein and D-lactate in S-AGI. RESULTS: Serum HPA and SCD-1 levels were significantly reduced in the intervention group compared with the control group (P < 0.05). In addition, intestinal fatty acid-binding protein, D-lactate, AGI grade, motilin, and gastrin levels and sequential organ failure assessment score were significantly decreased (P < 0.05) in the intervention group. However, LC3B, APTT, anti-Xa factor, and CD4/CD8 were significantly increased (P < 0.05) in the intervention group. No significant differences in interleukin-6, tumour necrosis factor-α, d-dimer, acute physiology and chronic health evaluation II score, length of ICU stay, length of hospital stay, or 28-d survival were noted between the two groups (P > 0.05). Correlation analysis revealed a significant negative correlation between HPA and LC3B and a significant positive correlation between HPA and AGI grade. ROC curve analysis showed that HPA had higher specificity and sensitivity in diagnosis of S-AGI. CONCLUSION: HPA has great potential as a diagnostic marker for S-AGI. Inhibition of HPA activity reduces SDC-1 shedding and alleviates S-AGI symptoms. The inhibitory effect of HPA in gastrointestinal protection may be achieved by enhanced autophagy.

Mechanism of symbiotic nodulation between nitrogen and peanut.

Nitrogen is critical for peanut growth and development, and symbiotic nodulation and nitrogen fixation is one of the main ways for peanut to obtain nitrogen. The influence of exogenous nitrogen on nodule nitrogen fixation involves complex regulatory mechanisms, revealing the regulatory mechanisms of nitrogen on nodule nitrogen fixation is of great significance for realizing the potential of biological nitrogen fixation. In this review, we summarize the mechanism of "Crack entry" in the formation of peanut root nodule, the mechanism of symbiotic nodulation and quantitative regulation of peanut, and the regulatory mechanism of nitrogen affecting peanut nodulation. At present, the molecular mechanism by which nitrogen affects the interaction between Bradyrhizobium and peanut, thereby regulating nodulation, is still unclear. Therefore, future research should focus on the signal exchange, nodule number regulation, and nutrient exchange mechanism of nitrogen effects on Bradyrhizobium and peanut, which would provide a theoretical basis for improving nodule nitrogen fixation efficiency and peanut yield, and reduce chemical nitrogen fertilizer application.