Isolation and biological activity of six new polyketide and terpenoid derivatives from Neopestalotiopsis Clavispora AL01.

A fungus strain, Neopestalotiopsis clavispora AL01, was isolated from the leaf spot of the plant Phoenix dactylifera. Further chemical investigation of the fermentation extract of this strain afforded six new secondary metabolites (1-6), along with 11 known compounds (7-17) which included a new natural compound (7). Their structures were determined by extensive spectroscopic analysis including one-and two-dimensional (1D and 2D) NMR spectroscopy, high-resolution electrospray ionization mass spectrometry (HRESIMS), and ECD and NMR calculations. All compounds were evaluated for their phytotoxic activities. Among them, compounds 10, 12 and 13 exhibited phytotoxic activities against Nicotiana tabacum. Compound 3 exhibited weak antibacterial activity against methicillin-resistant Staphylococcus aureus, Micrococcus luteus and Vibrio harveyi. Taken collectively, these findings establish a solid research foundation for future investigations on bioactive natural products derived from phytopathogenic fungi.

Countermeasures and Application Effect of Nursing Interventions in Maintenance Hemodialysis Patients with Complications of Secondary Hyperparathyroidism.

Background: Secondary hyperparathyroidism commonly arises in individuals with end-stage kidney disease, especially those who undergo maintenance hemodialysis (MHD). This study investigated strategies and effectiveness of nursing interventions in MHD patients with secondary hyperparathyroidism complications. Methodology: This study is a retrospective analysis conducted at the General Hospital of Northern Theater Command. From June 2021 to June 2023, 212 patients undergoing MHD were selected for the study. They were divided into 2 groups based on their parathyroid hormone levels: a hyperthyroidism group and a standard group. Within the hyperthyroidism group, participants were randomly assigned to either the control group (CG), which received routine nursing, or the observation group (OG), which received targeted nursing. The study assessed several primary outcome measures, including patient risk factors, nursing satisfaction, psychological status, quality of life, treatment compliance, and nutritional indexes. Results: Significant disparities existed in the age, diabetes presence, pulse pressure, duration of dialysis, and levels of creatinine, C-reactive protein, phosphorus, triglyceride, albumin, calcium, and phosphorus product between the hyperthyroidism and the standard group. The duration of dialysis, presence of diabetes, C-reactive protein, and blood phosphorus were identified as independent risk factors for maintaining secondary hyperparathyroidism in patients undergoing hemodialysis. Overall satisfaction with nursing care and compliance with treatment were significantly higher in the observation group compared to the CG. Following nursing care, the scores on the Self-rating Anxiety Scale and the Self-rating Depression Scale were substantially lower in the OG compared to the CG. After nursing care, the biochemical indicators were lower, the nutritional indicators were higher, and the quality of life scores were significantly improved in the OG compared to the CG. Conclusion: Targeted nursing interventions in the care of hemodialysis patients with hyperparathyroidism enhanced serological markers, alleviated negative emotions, and improved patients' quality of life and nutritional status.

Abnormal function of EPHA2/p.R957P mutant in congenital cataract.

AIM: To identify genetic defects in a Chinese family with congenital posterior polar cataracts and assess the pathogenicity. METHODS: A four-generation Chinese family affected with autosomal dominant congenital cataract was recruited. Nineteen individuals took part in this study including 5 affected and 14 unaffected individuals. Sanger sequencing targeted hot-spot regions of 27 congenital cataract-causing genes for variant discovery. The pathogenicity of the variant was evaluated by the guidelines of American College of Medical Genetics and InterVar software. Confocal microscopy was applied to detect the subcellular localization of fluorescence-labeled ephrin type-A receptor 2 (EPHA2). Co-immunoprecipitation assay was implemented to estimate the interaction between EphA2 and other lens membrane proteins. The mRNA and protein expression were analyzed by reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting assay, respectively. The cell migration was analyzed by wound healing assay. Zebrafish model was generated by ectopic expression of human EPHA2/p.R957P mutant to demonstrate whether the mutant could cause lens opacity in vivo. RESULTS: A novel missense and pathogenic variant c.2870G>C was identified in the sterile alpha motif (SAM) domain of EPHA2. Functional studies demonstrated the variant's impact: reduced EPHA2 protein expression, altered subcellular localization, and disrupted interactions with other lens membrane proteins. This mutant notably enhanced human lens epithelial cell migration, and induced a central cloudy region and roughness in zebrafish lenses with ectopic expression of human EPHA2/p.R957P mutant under differential interference contrast (DIC) optics. CONCLUSION: Novel pathogenic c.2870G>C variant of EPHA2 in a Chinese congenital cataract family contributes to disease pathogenesis.

A V-shaped association between high-density lipoprotein cholesterol levels and poor outcomes in patients after percutaneous coronary intervention.

BACKGROUND: High density lipoprotein cholesterol (HDL-C) is considered as "good cholesterol". Recent evidence suggests that a high HDL-C level may increase the risk of poor outcomes in some populations. PURPOSE: To investigate the association between HDL-C levels and poor outcomes in patients after percutaneous coronary intervention (PCI). METHODS: Patients undergoing PCI during January 2012 and December 2018 were consecutively recruited and divided into three groups with different HDL-C levels: HDL-C ≤ 25 mg/dL, 25 < HDL-C ≤ 60 mg/dL, HDL-C > 60 mg/dL by the restricted cubic spline (RCS) analysis and assessed for all-cause mortality (ACM). The association between HDL-C levels and poor outcomes was assessed by multivariable cox regression analysis. RESULTS: The patients were followed with a median duration of 4 years. Of the 7284 participants, 727 all-cause deaths and 334 cardiovascular deaths occurred. A V-shaped association of HDL-C with the prognosis was observed, patients with either excessively low or high HDL-C levels reporting a higher risk than those with midrange values. After adjustment for confounding factors, the former exhibited a higher cumulative rate of ACM and cardiovascular mortality (CM) than the latter [low HDL-C: for ACM, hazard ratio (HR), 1.96; 95%CI, 1.41, 2.73, P < 0.001; for CM, HR, 1.66; 95%CI, 1.03, 2.67; P = 0.037; high HDL-C: for ACM, HR, 1.73; 95%CI, 1.29, 2.32, P < 0.001; for CM, HR, 1.73; 95%CI, 1.16, 2.58; P = 0.007]. CONCLUSION: HDL-C levels display a V-shaped association with poor outcomes in patients after PCI, with excessively high or low HDL-C suggesting a higher mortality risk. An optimal HDL-C level may fall in the range of 25-60 mg/dL.

Efficacy of modified kidner procedure combined with subtalar arthroereisis treating adolescent type 2 painful accessory navicular with flexible flatfoot.

Purpose: To investigate the clinical efficacy of modified kidner procedure combined with subtalar arthroereisis in the treatment of adolescent type II painful accessory navicular with flexible flatfoot. Methods: From January 2018 to January 2022, 25 adolescent patients (40 feet) with painful type II accessory navicular and flexible flatfoot admitted to our hospital were enrolled in the study, including 13 males (23 feet) and 12 females (17 feet). All patients underwent modified kidner procedure combined with subtalar joint arthrodesis. The Meary's Angle, the first metatarsal Angle of talus (APTMT), the second metatarsal Angle of talus, Pitch Angle, talus tilt Angle, talonavicular coverage Angle (TCA), talus calcaneal Angle (LTCA), and calcaneal Angle were measured on weight-bearing anteroposterior and lateral x-ray films before operation and at last follow-up. The American Orthopaedic Foot and Ankle Society (AOFAS) midfoot score and visual analogue scale (VAS) were used to evaluate the improvement of foot function and pain. Results: All patients were followed up for average 17.4 ± 2.6 months (12-24). The incisions of 25 patients healed by first intention. The weight-bearing anteroposterior and lateral x-ray films of the foot showed that the suture anchors did not pull out or break, and the foot arch did not collapse further. There was no screw withdrawal or secondary operation to remove the screw in all patients. At the last follow-up, the postoperative visual analogue scale (VAS) score of the affected foot was significantly lower than that before operation (P < 0.01), and the American Orthopaedic Foot and Ankle Society (AOFAS) foot function score was significantly higher than that before operation (P < 0.01). At the last follow-up, the weight-bearing anteroposterior and lateral foot x-ray films showed that: The Meary's Angle, the first metatarsal Angle of the talus (APTMT), the second metatarsal Angle of the talus, Pitch Angle, talar tilt Angle, talonavicular overbite Angle (TCA), talocalcaneal Angle (LTCA), and calcaneal Angle significantly improved when compared with those before operation (P < 0.01). Conclusions: The modified kidner procedure combined with subtalar arthroereisis has a good clinical effect in the treatment of adolescent type II painful accessory navicular with flexible flatfoot, which can effectively improve the pain symptoms, improve the foot function and imaging manifestations, and correct the flatfoot deformity.

Electroencephalogram-Based Subject Matching Learning (ESML): A Deep Learning Framework on Electroencephalogram-Based Biometrics and Task Identification.

An EEG signal (Electroencephalogram) is a bioelectric phenomenon reflecting human brain activities. In this paper, we propose a novel deep learning framework ESML (EEG-based Subject Matching Learning) using raw EEG signals to learn latent representations for EEG-based user identification and tack classification. ESML consists of two parts: one is the ESML1 model via an LSTM-based method for EEG-user linking, and one is the ESML2 model via a CNN-based method for EEG-task linking. The new model ESML is simple, but effective and efficient. It does not require any restrictions for EEG data collection on motions and thinking for users, and it does not need any EEG preprocessing operations, such as EEG denoising and feature extraction. The experiments were conducted on three public datasets and the results show that ESML performs the best and achieves significant performance improvement when compared to baseline methods (i.e., SVM, LDA, NN, DTS, Bayesian, AdaBoost and MLP). The ESML1 model provided the best precision at 96% with 109 users and the ESML2 model achieved 99% precision at 3-Class task classification. These experimental results provide direct evidence that EEG signals can be used for user identification and task classification.

Virtual screening of novel mTOR inhibitors for the potential treatment of human colorectal cancer.

The abnormal activation of the mTOR pathway is closely related to the occurrence and progression of cancer, especially colorectal cancer. In this study, a rational virtual screening strategy has been established and MT-5, a novel mTOR inhibitor with a quinoline scaffold, was obtained from the ChemDiv database. MT-5 showed potent kinase inhibitory activity (IC50: 8.90 µM) and antiproliferative effects against various cancer cell lines, especially HCT-116 cells (IC50: 4.61 µM), and this was 2.2-fold more potent than that of the cisplatin control (IC50: 9.99 µM). Western blot, cell migration, cycle arrest, and apoptosis assays were performed with HCT-116 cells to investigate the potential anticancer mechanism of MT-5. Metabolic stability results in vitro indicated that MT-5 exhibited good stability profiles in artificial gastrointestinal fluids, rat plasma, and liver microsomes. In addition, the key contribution of the residues around the binding pocket of MT-5 in binding to the mTOR protein was also investigated from a computational perspective.

Prognostic value of triglyceride glucose index in population at high cardiovascular disease risk.

BACKGROUND: Early identification of populations at high cardiovascular disease (CVD) risk and improvement of risk factors can significantly decrease the probability of CVD development and improve outcomes. Insulin resistance (IR) is a CVD risk factor. The triglyceride glucose (TyG) index is a simple and reliable index for evaluating IR. However, no clinical studies on the prognostic value of the TyG index in a high risk CVD population have been conducted. This study evaluated the relationship between the TyG index and prognosis in a high risk CVD population. METHODS: This study enrolled 35,455 participants aged 35-75 years who were at high CVD risk and visited selected health centers and community service centers between 2017 and 2021. Their general clinical characteristics and baseline blood biochemical indicators were recorded. The TyG index was calculated as ln[fasting triglyceride (mg/dl)× fasting blood glucose (mg/dl)/2]. The endpoints were all-cause death and cardiovascular death during follow-up. Cox proportional hazard models and restricted cubic spline (RCS) analysis were used to evaluate the correlation between the TyG index and endpoints. RESULTS: In the overall study population, the mean age of all participants was 57.9 ± 9.6 years, 40.7% were male, and the mean TyG index was 8.9 ± 0.6. All participants were divided into two groups based on the results of the RCS analysis, with a cut-off value of 9.83. There were 551 all-cause deaths and 180 cardiovascular deaths during a median follow-up time of 3.4 years. In the multivariate Cox proportional hazard model, participants with a TyG index ≥ 9.83 had a higher risk of all-cause death (Hazard ratio [HR] 1.86, 95% Confdence intervals [CI] 1.37-2.51, P<0.001) and cardiovascular death (HR 2.41, 95%CI 1.47-3.96, P = 0.001) than those with a TyG index < 9.83. Subgroup analysis revealed that there was no interaction between the TyG index and variables in all subgroup analyses. CONCLUSIONS: The high TyG index was associated with an increased risk of all-cause death and cardiovascular death in people at high risk of CVD. This finding demonstrates the value of the TyG index in the primary prevention of CVD. TRIAL REGISTRATION: retrospectively registered, the registration number is K2022-01-005 and the date is 2022.01.30.

[Advances in Microbial Degradation and Transformation of Per- and Polyfluoroalkyl Substances(PFASs)].

Per- and polyfluoroalkyl substances (PFASs) have attracted extensive attention because of their persistence, long-distance migration ability, bioaccumulation, and biological toxicity. Currently, regulatory strategies concerning PFASs in the environment primarily focus on perfluoroalkyl acids (PFAAs). However, most polyfluoroalkyl compounds can be degraded to PFAAs by environmental microorganisms, also known as precursors. Exploring the microbial transformation behavior of precursors is fundamental to comprehensively evaluate the environmental risk of PFASs and formulate control and remediation schemes of PFAS-contaminated sites. Furthermore, anaerobic microbial reductive defluorination of PFAAs is a potential and challenging remediation technology. This review summarizes degradation rules and transformation pathways of precursors (fluorotelomer compounds and perfluorooctane sulfonamide derivatives), PFAAs, and novel PFASs by microorganisms and discusses factors affecting the microbial degradation. Finally, the future research directions are put forward.

The Treatment Combining Antiangiogenesis with Chemoradiotherapy Impinges on the Peripheral Circulation Vascular Endothelial Cells and Therapeutic Effect in the Patients with Locally Advanced Nasopharyngeal Carcinoma.

This study was implemented for the evaluation on the circulating endothelial cells' (CECs) clinical significance in the locally advanced nasopharyngeal carcinoma treatment with endostatin-combined chemoradiotherapy. This study enrolled 47 patients with locally advanced nasopharyngeal carcinoma who were hospitalized from May 9, 2012 to March 10, 2013. These patients were split up into the observation group (25 patients) and control group (22 patients). Patients in the observation group received the endostatin combined with induction chemotherapy and subsequently with concurrent chemoradiotherapy with endostatin. Patients in the control group were treated with inductive chemotherapy followed by concurrent chemoradiotherapy. CECs in peripheral blood were conducted separately before or after inductive chemotherapy and additionally in the end of concurrent chemoradiotherapy. The CEC values of the observation group showed significant statistical differences (p < 0.05) before or after different therapies, whereas those data in the control group were not statistically different. And, the mostly importantly, the CEC values in the observation group and control group turned out a statistical difference. The combination of endostatin and chemoradiotherapy significantly reduced parameters of peripheral blood CECs in these patients. According to the CEC parameters' variety that we observed in the combined therapies, this study demonstrated that the CECs might be a clinical clue to evaluate this antiangiogenic chemoradiotherapy. And the clinical value of CECs will be further determined along with increasing comparative studies and clinical long-term efficacy observation.