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Aim: The aim of this study is to explore the perceptions of Chinese registered nurses on toxic leadership behaviours of nurse managers and to determine its type, cause and response measures. Background: The nurse manager is the front‐line leader of the nurses who provide services directly to patients. Previous evidence suggests that toxic leadership behaviours of nurse managers do exist and it is necessary to understand the specifics of it. Methods: We used phenomenological research methods to conduct semi‐structured in‐depth interviews among 12 nurses at a tertiary hospital in Wuhan over the period from January to March 2022. And the data were analysed using Colaizzi seven‐step analysis method. Results: Four themes were discovered: (a) nurses' perceptions of toxic leadership behaviours; (b) toxic leadership behaviours of nurse managers; (c) reasons for toxic leadership behaviours of nurse managers and (d) measures for toxic leadership behaviours of nurse managers. Conclusion: Chinese nurses are exposed to the toxic leadership of nurse managers for multiple reasons and respond differently. Implications for Nursing Management: This study helps nursing managers identify which behaviours are harmful to the nurse that require special attention in developing strategies to buffer against nurse managers' toxic leadership. [ABSTRACT FROM AUTHOR]

• COVID-19 can cause a series of clinical symptoms. • The lung is the organ most affected by infection of SARS-CoV-2. • Interventions should be implemented to help recovery of healthcare workers with COVID-19. This study aimed to evaluate the recovery of functional fitness, lung function, and immune function in healthcare workers (HCWs) with nonsevere and severe COVID-19 at 13 months after discharge from the hospital. The participants of "Rehabilitation Care Project for Medical Staff Infected with COVID-19" underwent a functional fitness test (muscle strength, flexibility, and agility/dynamic balance), lung function test, and immune function test (including cytokines and lymphocyte subsets) at 13 months after discharge. The project included 779 HCWs (316 nonsevere COVID-19 and 463 severe COVID-19). This study found that 29.1% (130/446) of the HCWs have not yet recovered their functional fitness. The most affected lung function indicator was lung perfusion capacity (34% with diffusion capacity for carbon monoxide-single breath <80%). The increase of interleukin-6 (64/534, 12.0%) and natural killer cells (44/534, 8.2%) and the decrease of CD3+ T cells (58/534, 10.9%) and CD4+ T cells (26/534, 4.9%) still existed at 13 months after discharge. No significant difference was found in the HCWs with nonsevere and severe COVID-19 regarding recovery of functional fitness, lung function, and immune function at 13 months after discharge. The majority of Chinese HCWs with COVID-19 had recovered their functional fitness, lung function, and immune function, and the recovery status in HCWs with severe COVID-19 is no worse than that in HCWs with nonsevere COVID-19 at 13 months after discharge from the hospital. [ABSTRACT FROM AUTHOR]

Background: Few studies had described the health consequences of patients with coronavirus disease 2019 (COVID-19) especially in those with severe infections after discharge from hospital. Moreover, no research had reported the health consequences in health care workers (HCWs) with COVID-19 after discharge. We aimed to investigate the health consequences in HCWs with severe COVID-19 after discharge from hospital in Hubei Province, China.Methods: We conducted an ambidirectional cohort study in "Rehabilitation Care Project for Medical Staff Infected with COVID-19" in China. The participants were asked to complete three physical examinations (including the tests of functional fitness, antibodies to SARS-CoV-2 and immunological indicators) at 153.4 (143.3, 164.8), 244.3 (232.4, 259.1), and 329.4 (319.4, 339.3) days after discharge, respectively. Mann-Whitney U test, Kruskal-Wallis test, t test, one-way ANOVA, χ2, and Fisher's exact test were used to assess the variance between two or more groups where appropriate.Results: Of 333 HCWs with severe COVID-19, the HCWs' median age was 36.0 (31.0, 43.0) years, 257 (77%) were female, and 191 (57%) were nurses. Our research found that 70.4% (114/162), 48.9% (67/137), and 29.6% (37/125) of the HCWs with severe COVID-19 were considered to have not recovered their functional fitness in the first, second, and third functional fitness tests, respectively. The HCWs showed improvement in muscle strength, flexibility, and agility/dynamic balance after discharge in follow-up visits. The seropositivity of IgM (17.0% vs. 6.6%) and median titres of IgM (3.0 vs. 1.4) and IgG (60.3 vs. 45.3) in the third physical examination was higher than that in the first physical examination. In the third physical examination, there still were 42.1% and 45.9% of the HCWs had elevated levels of IL-6 and TNF-α, and 11.9% and 6.3% of the HCWs had decreased relative numbers of CD3+ T cells and CD4+ T cells.Conclusion: The HCWs with severe COVID-19 showed improvement in functional fitness within 1 year after discharge, active intervention should be applied to help their recovery if necessary. It is of vital significance to continue monitoring the functional fitness, antibodies to SARS-CoV-2 and immunological indicators after 1 year of discharge from hospital in HCWs with severe COVID-19. [ABSTRACT FROM AUTHOR]

Attitude determination of the space vehicle always plays a pivotal role in space missions. Usually, the fourth-order Runge Kutta algorithm is taken as more common attitude integration algorithm. However, more appropriate algorithms are desired in order to meet variable requirement. This paper investigates the performance of the fourth-order Runge Kutta and Taylor series algorithms in coning environment, and presents a new algorithm which takes advantages from above both. Series of simulation experiments have been conducted to verify the effect of the new algorithm. Their results show that the new algorithm outperforms the fourth-order Runge Kutta and the four-sample rotation vector algorithms over long-duration run even in complex engineering applications where the attitude change is not too fast. [ABSTRACT FROM AUTHOR]

• The authors designed novel GPR119 agonists bearing various core moiety from lipophilic cycloolefin fused pyrimidines to polar tetrahydropyridopyrimidines and found that the less polar cyclohexene fused compounds displayed the most potent activity. A novel series of fused pyrimidine derivatives were designed, synthesized and evaluated as GPR119 agonists. Among them, cyclohexene fused compounds (tetrahydroquinazolines) showed greater GPR119 agonistic activities than did dihydrocyclopentapyrimidine and tetrahydropyridopyrimidine scaffolds. Analogues (16 , 19 , 26 , 28 , 42) bearing endo - N -Boc-nortropane amine and fluoro-substituted aniline exhibited better EC 50 values (0.27–1.2 μM) though they appeared to be partial agonists. [ABSTRACT FROM AUTHOR]

Cantharidin (CTD) is a principal bioactive component of traditional Chinese medicine Mylabris used in cancer treatment. However, CTD clinical application is limited due to nephrotoxicity, and the mechanism is unknown. The present study used widely-targeted metabolomics, network pharmacology, and cell experiments to investigate the nephrotoxicity mechanism after CTD exposure. In mice exposed to CTD, serum creatinine and urea nitrogen levels increased with renal injury. Then, 74 differential metabolites were detected, including 51 up-regulated and 23 down-regulated metabolites classified as amino acids, small peptides, fatty acyl, arachidonic acid metabolite, organic acid, and nucleotides. Sixteen metabolic pathways including tyrosine, sulfur, and pyrimidine metabolism were all disrupted in the kidney. Furthermore, network pharmacology revealed that 258 metabolic targets, and pathway enrichment indicated that CTD could activate oxidative phosphorylation and oxidative stress (OS). Subsequently, HK-2 cell experiments demonstrated that CTD could reduce superoxide dismutase while increasing malondialdehyde levels. In conclusion, after CTD exposure, biometabolic processes may be disrupted with renal injury in mice, resulting in oxidative phosphorylation and OS. [ABSTRACT FROM AUTHOR]

The binding of programmed death 1 (PD-1) to its ligands PD-L1 and PD-L2 on antigen-presenting cells has been proven to turn off autoreactive T cells and induce peripheral tolerance. In this study, fusion proteins linking the extracellular domains of murine PD-1, PD-L1 and PD-L2 to the Fc portion of a mouse immunoglobulin G2a monoclonal antibody were generated and characterized. Onset of proteinuria was delayed with mice treated with PD-LIg fusion proteins, while serum concentrations of anti-dsDNA and anti-histone antibodies were reduced by the treatment of PD-LIg without decreasing total IgG with significantly improved survival. Importantly, PD-L1Ig treatment was the most efficacious in delaying the onset of proteinuria, blocking auto-antibody production, and prolonging life time, including a delayed treatment until disease progression. These findings indicate that human PD-L1Ig fusion proteins may play an important role in conquering humans' autoimmune diseases. [ABSTRACT FROM AUTHOR]

Although several studies have reported testicular impairments caused by cadmium (Cd) or obesity alone, the combined effect of Cd and obesity on the testes and its underlying mechanism remains unclear. We examined the combined effect of whole-life exposure to low-dose Cd started at preconception and post-weaning high-fat diet (HFD) on the testes of offspring mice. At weaning, male offspring parented with and without exposure to low-dose Cd were continued on the same drinking water regimen as their parents and fed with either a normal diet (ND) or HFD for 10 or 24 weeks. Whole-life exposure to Cd resulted in its accumulation in testes, and HFD induced obesity and lipid metabolism disorder. Exposure to Cd or HFD alone significantly decreased Johnsen scores, disrupted testicular structure, and increased germ cell apoptosis at both 10 and 24 weeks. However, co-exposure to Cd and HFD did not induce the toxic effects that were induced by either alone, as revealed by preserved testicular structure and spermatogenesis, lack of significant apoptosis, and increased cell proliferation. Mechanistically, the combined effects of low-dose Cd and HFD consumption were associated with the activation of the JAK/STAT pathway. These findings suggest that co-exposure to low-dose Cd and HFD did not cause Cd- or HFD-induced testicular injury, probably because of the activation of the JAK/STAT pathway to prevent germ cell apoptosis. [Display omitted] • Tested the effects of whole-life low-dose Cd exposure and HFD on mouse offspring testes. • Either exposure to cadmium (Cd) or high-fat diet (HFD) alone induced testicular injury. • Co-exposure to Cd and HFD did not show significant testicular damage. • Lack of synergistic or additive effects of both may be related with JAK/STAT activation. [ABSTRACT FROM AUTHOR]

To investigate the factors that influence readmissions in patients with acute non-ST elevation myocardial infarction (NSTEMI) after percutaneous coronary intervention (PCI) by using multiple machine learning (ML) methods to establish a predictive model. In this study, 1576 NSTEMI patients who were hospitalized at the Affiliated Hospital of North Sichuan Medical College were selected as the research subjects. They were divided into two groups: the readmitted group and the non-readmitted group. The division was based on whether the patients experienced complications or another incident of myocardial infarction within one year after undergoing PCI. Common variables selected by univariate and multivariate logistic regression, LASSO regression, and random forest were used as independent influencing factors for NSTEMI patients' readmissions after PCI. Six different ML models were constructed using these common variables. The area under the ROC curve, accuracy, sensitivity, and specificity were used to evaluate the performance of the six ML models. Finally, the optimal model was selected, and a nomogram was created to visually represent its clinical effectiveness. Three different methods were used to select seven representative common variables. These variables were then utilized to construct six different ML models, which were subsequently compared. The findings indicated that the LR model exhibited the most optimal performance in terms of AUC, accuracy, sensitivity, and specificity. The outcome, admission mode (walking and non-walking), communication ability, CRP, TC, HDL, and LDL were identified as independent predicators of readmissions in NSTEMI patients after PCI. The prediction model constructed by the LR algorithm was the best. The established column graph model established proved to be effective in identifying high-risk groups with high accuracy and differentiation. It holds a specific predictive value for the occurrence of readmissions after direct PCI in NSTEMI patients. [ABSTRACT FROM AUTHOR]

Background: Career maturity is a crucial indicator of career preparedness and unpreparedness can cause the turnover of new nurses. Considerable empirical work demonstrates the potential associations between specialty identity, self-efficacy, study engagement, and career maturity. This study aimed to explore the mediation role of self-efficacy and study engagement on the relationships between specialty identity and career maturity among Chinese nursing students. Methods: Four hundred twenty-six Chinese nursing students were recruited between September 11 and October 30, 2022. The online survey was conducted following the CHERRIES checklist. Electronic questionnaires assessed their perceived specialty identity, self-efficacy, study engagement, and career maturity. The descriptive analysis, Harman single-factor analysis, Pearson correlation tests, structural equation modeling, and the bootstrap method were employed in data analysis. Results: Bivariate correlation analysis identified a positive correlation between specialty identity, self-efficacy, study engagement, and career maturity (r = 0.276–0.440, P < 0.001). Self-efficacy and study engagement partially mediated the relationship between specialty identity and career maturity. Self-efficacy and study engagement played a chain mediating role between specialty identity and career maturity. Conclusions: The underlying mechanism can explain the relationships between specialty identity and career maturity: a direct predictor and an indirect effect through self-efficacy and study engagement. Policymakers and educators should emphasize the importance of specialty identity and provide tailored strategies for improving care maturity depending on nursing students' specialty identity, self-efficacy, study engagement in the early stages of career development. [ABSTRACT FROM AUTHOR]

Introduction: To assess the long-term consequences of coronavirus disease (COVID-19) among health care workers (HCWs) in China (hereafter surviving HCWs). Methods: A total of 303 surviving HCWs were included. Lung (pulmonary function test, 6-min walk test [6MWT], chest CT), physical (St. George's Respiratory Questionnaire [SGRQ], Modified Medical Research Council dyspnea scale [mMRC], and Borg scale), and psychiatric functions (Essen Trauma Inventory) were evaluated during the 1-year follow-up. Results: Surviving HCWs had an abnormal diffusion capacity 1 year post-discharge. Participants with a reduced carbon monoxide diffusing capacity (DLCO) comprised 43.48%. The proportion of HCWs with a median 6MWT distance below the lower limit of the normal was 19.4%. An abnormal CT pattern was observed in 37.5% of the HCWs. The SGRQ, mMRC, and Borg scores of surviving HCWs, especially those with critical/severe disease, were significantly higher than those in the normal population. Probable post-traumatic stress disorder (PTSD) was reported in 21.9% of the surviving HCWs. Diffusion capacity impairment was associated with women. Critical/severe illness and nurses were associated with impaired physical function. Conclusions: Most surviving HCWs, especially female HCWs, still had an abnormal diffusion capacity at 1 year. The physical and psychiatric functions of surviving HCWs were significantly worse than those of the healthy population. Long-term follow-up of pulmonary, physical, and psychiatric functions for surviving HCWs is required. [ABSTRACT FROM AUTHOR]

Aim: Tyrosine decarboxylase (TDC) presented in the gut‐associated strain Enterococcus faecalis can convert levodopa (L‐dopa) into dopamine (DA), and its increased abundance would potentially minimize the availability and efficacy of L‐dopa. However, the known human decarboxylase inhibitors are ineffective in this bacteria‐mediated conversion. This study aims to investigate the inhibition of piperine (PIP) on L‐dopa bacterial metabolism and evaluates the synergistic effect of PIP combined with L‐dopa on Parkinson's disease (PD). Methods: Metagenomics sequencing was adopted to determine the regulation of PIP on rat intestinal microbiota structure, especially on the relative abundance of E. faecalis. Then, the inhibitory effects of PIP on L‐dopa conversion and TDC expression of E. faecalis were tested in vitro. We examined the synergetic effect of the combination of L‐dopa and PIP on 6‐hydroxydopamine (6‐OHDA)‐lesioned rats and tested the regulations of L‐dopa bioavailability and brain DA level by pharmacokinetics study and MALDI‐MS imaging. Finally, we evaluated the microbiota‐dependent improvement effect of PIP on L‐dopa availability using pseudo‐germ‐free and E. faecalis‐transplanted rats. Results: We found that PIP combined with L‐dopa could better ameliorate the move disorders of 6‐OHDA‐lesioned rats by remarkably improving L‐dopa availability and brain DA level than L‐dopa alone, which was associated with the effect of PIP on suppressing the bacterial decarboxylation of L‐dopa via effectively downregulating the abnormal high abundances of E. faecalis and TDC in 6‐OHDA‐lesioned rats. Conclusion: Oral administration of L‐dopa combined with PIP can improve L‐dopa availability and brain DA level in 6‐OHDA‐lesioned rats by suppressing intestinal bacterial TDC. [ABSTRACT FROM AUTHOR]

Aim. The aim of this study is to analyse the toxic leadership behavior of nurse managers perceived by nurses and its related factors. Background. Toxic leadership is becoming more common as a risk factor in nursing. However, there is a scarcity of research on the elements that influence toxic leadership practices from the perspective of nurses' perceptions. Methods. A cross-sectional study was conducted with 455 nurses from August to October 2022. A demographic information questionnaire and a negative behavior scale for nurse managers were used. Descriptive statistics, Kruskal–Wallis H test or Mann–Whitney U test, and multiple linear regression were used to explore the relevant factors of nurses' perceived toxic leadership behaviors of nurse managers. Results. The population was dominated by 423 (92.97%) females, 318 (69.89%) married, and 420 (92.31%) with a bachelor's degree. The toxic leadership behavior scale score for nurse managers was 109 (87, 123) and the score for each entry was (2.94 ± 0.92). Gender, educational level, department, number of night shifts, and nature of employment were the influencing factors of the negative leadership behavior of nurse leaders as perceived by nurses (P < 0.05), explaining a total of 43.1% of the total variance. Conclusion. In general, nurses' perceived toxic leadership behaviors of nurse managers were at a moderate level. More toxic leadership behaviors were observed by nurses who were female, less educated, on busy units, with unstable nature of appointments, and with frequent night shift rotation. Implications for Nursing Management. Focus on the psychological condition of nurses who are female, less educated, work in busy units, have an unstable nature of employment, and rotate night shifts frequently. The negative impacts of toxic leadership behaviors might be lessened as a result. [ABSTRACT FROM AUTHOR]

Noninvasive genetic sampling greatly facilitates studies on the genetics, ecology, and conservation of threatened species. Species identification is often a prerequisite for noninvasive sampling‐based biological studies. Due to the low quantity and quality of genomic DNA from noninvasive samples, high‐performance short‐target PCR primers are necessary for DNA barcoding applications. The order Carnivora is characterized by an elusive habit and threatened status. In this study, we developed three pairs of short‐target primers for identifying Carnivora species. The COI279 primer pair was suitable for samples with better DNA quality. The COI157a and COI157b primer pairs performed well for noninvasive samples and reduced the interference of nuclear mitochondrial pseudogenes (numts). COI157a could effectively identify samples from Felidae, Canidae, Viverridae, and Hyaenidae, while COI157b could be applied to samples from Ursidae, Ailuridae, Mustelidae, Procyonidae, and Herpestidae. These short‐target primers will facilitate noninvasive biological studies and efforts to conserve Carnivora species. [ABSTRACT FROM AUTHOR]

Aims: This study aimed to analyse the prevalence of nurse‐to‐nurse horizontal violence in Chinese hospitals and examine the effects of head nurse's caring and nurse's group behaviour on horizontal violence. Background: Horizontal violence is a serious global problem affecting the nursing profession, but little is known of the issue in Chinese hospitals. Increasing evidence has showed that leadership and group factors are important in facilitating horizontal violence. Whether the head nurse's caring and group behaviour perceived by nurses has protective effects against horizontal violence remains unclear. Methods: A cross‐sectional online‐based questionnaire study was performed in seven general hospitals in Hubei Province, China. Data related to the demographic information, horizontal violence, head nurse's caring and group behaviour were collected. Descriptive analyses, chi‐squared tests and logistic regression were used for data analysis. Results: In total, 1942 valid questionnaires were collected, with a 92.70% effective response rate (1942/2095). Of those, 59.1% (1148/1942) of respondents had experienced horizontal violence at least once in the previous 6 months. Covert negative behaviours were more frequently reported. Compared with the low level, moderate and high levels of the head nurse's caring showed a lower risk of horizontal violence (odds ratio [OR] = 0.400, p <.001; OR = 0.128, p <.001); moderate and high levels of group behaviour also showed a reduced risk (OR = 0.601, p <.001; OR = 0.221, p <.001). Conclusion: Horizontal violence is common among Chinese nurses. The head nurse's caring and maintaining a good climate of nurses' group behaviours could serve as protective factors for preventing horizontal violence. Implications for Nursing Management: This study helps nursing managers identify which specific negative behaviours occur frequently and require special attention. It suggests that nursing managers attach importance to improving their caring ability towards nurses and to creating an amicable climate of group behaviour to buffer against horizontal violence. [ABSTRACT FROM AUTHOR]

Bacterial vaginosis (BV) is a genital infection that frequently presents in women infected with human papillomavirus (HPV), but the correlation between BV, HPV and cervical intraepithelial neoplasia (CIN) development is still elusive. We organized a cross-sectional analysis which enrolled 624 participants and obtained 423 samples of vaginal secretions from them, including 193 HPV-negative samples and 230 HR-HPV-positive samples. We used 16S rRNA sequencing to measure the vaginal microbiota diversity in women with different BV, HPV and CIN status, and then calculated risk factors for CIN by logistic regression. We found that the diversity of vaginal microbiota was significantly increased after BV, HPV and BV-infected CIN group. The Observed species and Chao1 index of H.C group showed little difference with normal group, while its Shannon index was considerable higher than normal group. L. iners enriched in HPV infection group compared with others significantly. BV (OR = 0.358; 95% CI = 0.195–0.656; P <.05) and HR-HPV infection (OR = 0.016; 95% CI = 0.004–0.072; P <.001) were risk factors for CIN. In conclusion, we consider BV as a risk factor for CIN. The enrichment of L. iners under HPV infection state may contribute to maintenance of vaginal dysbiosis, and BV infection could facilitate the disturb. [ABSTRACT FROM AUTHOR]

Piper longum L., a medicinal and food homologous herb, has a traditional history of use in treating gastrointestinal and neurological disorders. Piperine (PIP) the main alkaloid of P. longum , exists neuroprotective effects on various animal models of Parkinson's disease (PD). Nevertheless, the underlying mechanism, particularly the role of PIP in promoting gut-brain autophagy for α-Synuclein (α-Syn) degradation in PD, remains incompletely understood. To explore the role of PIP in regulating the gut-brain autophagy signaling pathway to reduce α-Syn levels in both the colon and substantia nigra (SN) of PD model rats. Behavioral experiments were conducted to assess the impact of PIP on 6-hydroxydopamine (6-OHDA)-induced PD rats. The intestinal microbiome composition and intestinal metabolites were analyzed by metagenomics and GC-MS/MS. The auto-phagosomes were visualized by transmission electron microscopy. Immunohistochemistry, immunofluorescence, and western blotting were performed to assess the levels of tyrosine hydroxylase (TH), α-Syn, LC3II/LC3I, p62, and the PI3K/AKT/mTOR pathway in both the SN and colon of the rats. The pathway-related inhibitor and agonist were used to verify the autophagy mechanism in the SH-SY5Y cells overexpressing A53T mutant α-Syn (A53T-α-Syn). PIP improved autonomic movement and gastrointestinal dysfunctions, reduced α-Syn aggregation and attenuated the loss of dopaminergic neurons in 6-OHDA-induced PD rats. After oral administration of PIP, the radio of LC3II/LC3I increased and the expression of p62 was degraded, as well as the phosphorylation levels of PI3K, AKT and mTOR decreased in the SN and colon of rats. The effect of PIP on reducing A53T-α-Syn through the activation of the PI3K/AKT/mTOR-mediated autophagy pathway was further confirmed in A53T-α-Syn transgenic SH-SY5Y cells. This effect could be inhibited by the autophagy inhibitor bafilomycin A1 and the PI3K agonist 740 Y–P. Our findings suggested that PIP could protect neurons by activating autophagy to degrade α-Syn in the SN and colon, which were related to the suppression of PIP on the activation of PI3K/AKT/mTOR signaling pathway. [Display omitted] • PIP improved behavioral impairments and gastrointestinal dysfunctions in 6-OHDA-induced PD rats. • PIP attenuated α-Synuclein accumulation in the colon and substantia nigra (SN) of PD rats. • PIP degraded pathological α-Syn by promoting gut-brain autophagy via suppressing PI3K/AKT/mTOR pathway. [ABSTRACT FROM AUTHOR]

Atrazine (ATR), a water-soluble herbicide commonly used to control broad-leaf and monocotyledonous weeds, presents a significant risk to environmental soil and water quality. Exposure to ATR adversely affects human and animal health, frequently resulting in cardiac impairment. Curcumin (Cur), an acidic polyphenol derivative from plants acclaimed for its pronounced anti-inflammatory and antioxidant properties, has garnered interest as a potential therapeutic agent. However, whether it has the potential to ameliorate ATR-induced cardiac toxicity via modulation of endoplasmic reticulum stress (ERS) and apoptosis pathways in mice remains unclear. Our results showed that Cur supplementation attenuates ATR-induced cardiotoxicity, evidenced by decrease in creatine kinase and lactate dehydrogenase, key biochemical markers of myocardial injury, which have a more significant protecting effect in high-dose ATR induced injury. Histopathological and electron microscopy examinations further solidified these findings, demonstrating an amelioration in organellar damage, particularly in endoplasmic reticulum swelling and subsequent mitochondrial impairment. Additionally, ATR exposure augments ERS and triggers apoptotic pathways, as indicated by the upregulation of ERS-related gene expression (ATF6, CHOP, IRE1, GRP78) and pro-apoptotic markers (BAX, BAK1, Caspase3, Caspase. Intriguingly, Cur counteracts this detrimental response, significantly reducing ERS and pro-apoptotic signals at both transcriptional and translational levels. Collectively, our findings illuminate Cur's cardioprotective effect against ATR-induced injury, primarily through its anti-ERS and anti-apoptotic activities, underscoring Cur's potential as a therapeutic for ATR-induced cardiotoxicity. [ABSTRACT FROM AUTHOR]

GPR119 is a promising target for discovery of anti-type 2 diabetes mellitus agents. We described the optimisation of a novel series of pyrimido[5,4-b][1,4]oxazine derivatives as GPR119 agonists. Most designed compounds exhibited good agonistic activities. Among them, compound 10 and 15 demonstrated the potent EC50 values (13 and 12 nM, respectively) and strong inherent activities. Moreover, significant hypoglycaemic effect of compound 15 was observed by reducing the blood glucose AUC0–2h at the dose of 30 mg/kg, which is stronger than Vildagliptin (23.4% reduction vs. 17.9% reduction). [ABSTRACT FROM AUTHOR]

Background: Staphylococcus aureus (S. aureus), including methicillin-susceptible S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA), is an eminent human pathogen that can colonize the human host and cause severe life-threatening infections. The development of a reliable, simple and rapid assay for detecting S. aureus and identifying MRSA is important for diagnosis and follow-up treatment. Methods: A novel molecular diagnosis technique, named multiplex loop-mediated isothermal amplification linked to a nanoparticle-based lateral flow biosensor (m-LAMP-LFB), was applied to detect all S. aureus species and identify MRSA. Two sets of primers were designed based on the femA gene (S. aureus-specific gene) and the mecA gene (encoding penicillin-binding protein 2a), and the multiple-LAMP products were analyzed using LFB. The m-LAMP-LFB amplification conditions, including the target DNA concentration, reaction temperature and time, were optimized. The sensitivity and specificity of the m-LAMP-LFB method were tested in the current study, and the multiple-LAMP-LFB technology was applied to detect the MSSA and MRSA strains from clinical samples. Results: The S. aureus- and MRSA-specific primers based on the femA and mecA genes allowed the multiple-LAMP technology to detect S. aureus and MRSA, respectively. The multiple-LAMP conditions were optimized at 63 °C for 40 min. The full process, including genomic DNA template preparation, LAMP, and product identification, could be achieved in 80 min. The limit of detection (LoD) of the multiple-LAMP assay for femA and mecA detection was 100 fg of genomic DNA template per reaction. The specificity of m-LAMP-LFB detection was 100 %, and no cross-reactions to non-S. aureus strains were observed. Conclusion: The multiple-LAMP-LFB technique developed in the current study is a reliable, simple, rapid, specific and sensitive method to identify MSSA and MRSA infections for appropriate antibiotic therapy. [ABSTRACT FROM AUTHOR]

Understanding the interaction between life history, demography and population genetics in threatened species is critical for the conservations of viable populations. In the context of habitat loss and fragmentation, identifying the factors that underpin the structuring of genetic variation within populations can allow conservationists to evaluate habitat quality and connectivity and help to design dispersal corridors effectively. In this study, we carried out a detailed, fine‐scale landscape genetic investigation of a giant panda population from the Qinling Mountains for the first time. With a large microsatellite data set and complementary analysis methods, we examined the role of isolation‐by‐barriers (IBB), isolation‐by‐distance (IBD) and isolation‐by‐resistance (IBR) in shaping the pattern of genetic variation in this giant panda population. We found that the Qinling population comprises one continuous genetic cluster, and among the landscape hypotheses tested, gene flow was found to be correlated with resistance gradients for two topographic factors, slope aspect and topographic complexity, rather than geographical distance or barriers. Gene flow was inferred to be facilitated by easterly slope aspect and to be constrained by topographically complex landscapes. These factors are related to benign microclimatic conditions for both the pandas and the food resources they rely on and more accessible topographic conditions for movement, respectively. We identified optimal corridors based on these results, aiming to promote gene flow between human‐induced habitat fragments. These findings provide insight into the permeability and affinities of giant panda habitats and offer important reference for the conservation of the giant panda and its habitat. [ABSTRACT FROM AUTHOR]

We described the discovery and optimization of a novel series of pyrimidopyrimidine derivatives as G-protein coupled receptor 119 (GPR119) agonists against type 2 diabetes. Most designed compounds displayed significant GPR119 agonistic activities. Optimized analogues 15a and 21e exhibited highly potent agonistic activities with single digit EC 50 values (2.2 nM and 8.1 nM, respectively). Therefore, 15a and 21e were evaluated for their oral glucose tolerance test (oGTT) in C57BL/6N mice. Compound 15a reduced the blood glucose area of under curve from 0 to 2 h (AUC 0–2h ) to 13.5% at the dose of 15 mg/kg comparing with Metformin reduced 18% of AUC 0–2h at the dose of 300 mg/kg. [ABSTRACT FROM AUTHOR]

Penthorum chinense Pursh. (PCP) is commonly used as a Miao ethnomedicine and health food for liver protection in China. Gansukeli (WS3–B-2526-97) is made from the extract of PCP (PCPE) for the treatment of viral hepatitis. In recent years, PCPE has been reported in the treatment of non-alcoholic fatty liver disease (NAFLD), however its potential mechanism is not fully elucidated. To investigate the ameliorating effect of PCPE on high-fat diet (HFD)-induced NAFLD mice and demonstrate whether its protective effect is gut microbiota dependent and associated with bile acid (BA) metabolism. The alleviating effect of PCPE on NAFLD was conducted on male C57BL/6J mice fed an HFD for 16 weeks, and this effect associated with gut microbiota dependent was demonstrated by pseudo-germfree mice treated with antibiotics and fecal microbiota transplantation (FMT). The composition of the gut microbiota in the cecum contents was analyzed by 16S rRNA sequencing, and the levels of BAs in liver and fecal samples were determined by UPLC/MS-MS. The results showed that administration of PCPE for 8 weeks could potently ameliorate HFD-induced NAFLD and alleviate dyslipidemia and insulin resistance. Moreover, PCPE treatment alleviated gut dysbiosis, especially reducing the relative abundance of bile salt hydrolase (BSH)-producing bacteria. Furthermore, PCPE significantly increased the levels of taurine-conjugated BAs in feces, such as tauro-β-muricholic acid (T-βMCA), tauroursodesoxycholic acid (TUDCA), and taurochenodeoxycholic acid (TCDCA), and increased hepatic chenodeoxycholic acid (CDCA). The protein and mRNA expression of farnesoid X receptor (FXR) and fibroblast growth factor 15 (FGF15) were decreased in intestine, increased taurine-conjugated BAs inhibited the intestinal signaling pathway, which was associated with increased genes expression of enzymes in the alternative BA synthesis pathway that reduced the levels of cholesterol. The increased CDCA produced via the alternative BA synthesis pathway promoted hepatic FXR activation and BA excretion. Our study is the first time to demonstrate that PCPE could ameliorate NAFLD in HFD-induced mice by regulating the gut microbiota and BA metabolism, and from a novel perspective, to clarify the mechanism of PCPE in NAFLD. [Display omitted] • Penthorum chinense Pursh. extract (PCPE) alleviating NAFLD in HFD-fed mice is gut microbiota dependent. • PCPE increases ileum conjugated bile acids levels via reducing the abundance of bile salt hydrolase-producing bacteria. • PCPE reduces liver lipid deposition by regulating the key genes FXR, FGF15, CYP27A1, and BSEP in bile acid metabolism. [ABSTRACT FROM AUTHOR]