Mechanism of Action of NvZhen ErXian HeJi in Ovariectomized Rats with Myocardial Infarction based on Network Pharmacology.

OBJECTIVE: Nv Zhen Er Xian He Ji (NZEXHJ) is used to treat perimenopausal syndrome (PS), but its effect on perimenopausal coronary heart disease is unclear. Furthermore, the aim of this research is to study the effect of NZEXHJ on perimenopausal coronary heart disease (PMCHD) in a rat model based on a network pharmacology approach. MATERIALS AND METHODS: Based on network pharmacological analysis combined with molecular docking, we predicted the potential therapeutic target and pharmacological mechanism of NZEXHJ in the treatment of PMCHD. We used an ovariectomized rat (OVR) model to understand the effect of NZEXHJ on myocardial injury and further verified the target of NZEXHJ in the intervention of PMCHD. RESULTS: We selected 52 active components of NZEXHJ against PMCHD and an intersection of their targets on network pharmacology, to which SCN5A, SER1, AR, and PGR were significantly correlated. The protein- protein interaction network revealed CASP3, CXCL8, IL6, MAPK1, TNF, TP53, and VEGFA in the treatment of PMCHD with NZEXHJ. Kaempferol, luteolin, and mistletoe presented good affinity towards the aforementioned targets by Molecular docking NZEXHJ exerted protecting cardiomyocytes for OVR. The mechanism was related to a reduction in the expression levels of the CXCL8, TNF, and regulating PI3K-AKT signaling pathways. CONCLUSION: This study reveals the potential multi-component, multi-target, and multi-pathway pharmacological effects of NZEXHJ and predicts its protection against myocardial infarction in ovariectomized rats through the PI3K Akt pathway, providing a theoretical basis for the treatment of PMCHD.

Schisandra chinensis lignans regulate and cooperate with endogenous cannabinoid systems to ameliorate intestinal barrier injury associated with depression.

BACKGROUND: Schisandra chinensis lignan (SCL), a major active component of the traditional functional Chinese medicine Schisandra chinensis, has been reported to have antidepressant effects. Its mechanisms include alleviating intestinal barrier injury (IBI) by resolving intestinal microflora, anti-inflammation, and neuroprotection. SCL also regulates endogenous cannabinoid system, and it is closely related to the onset and development of depression. PURPOSE: We investigated a new treatment strategy for depression, i.e., alleviating IBI by regulating the endogenous cannabinoid system for antidepressant effects, as well as conducted in-depth research to explore the specific mechanism. METHODS: Behavioral analysis was conducted to detect the occurrence of depressive-like behavior in C57BL/6 mice. We used hematoxylin-eosin staining, periodic acid-Schiff staining, and immunofluorescence to evaluate IBI. Network pharmacology and Western blotting (WB) were used to predict and confirm that the amelioration effect of SCL was associated with anti-inflammation and anti-apoptosis. Combined with the levels of anandamide (AEA) and 2-arachidonoylglycerol (2-AG), we conducted the Pearson analysis between the AEA, 2-AG levels and the major targets identified and validated by network pharmacology and WB. Subsequently, URB-597, a fatty acid amide hydrolase (FAAH) antagonist with an AEA hydrolase-inhibiting effect, was administered to the mice, and behavioral analysis and apoptotic proteins were verified. Plasma endocannabinoid levels after URB-597 supplementation were measured via 6470 Triple Quadrupole LC/MS. Finally, the cannabinoid receptor type 2 (CB2R) antagonist AM630 was administered to mice, and immunofluorescence and WB were performed to assess the proteins of IBI and anti-inflammation. RESULTS: The study demonstrated that SCL alleviated depressive-like behaviours and ameliorated IBI. Network pharmacology and WB confirmed that the improvement of IBI was related to the anti-inflammatory and anti-apoptotic pathways. Pearson results showed that AEA levels were positively correlated with inflammation and apoptosis, with a greater contribution to apoptosis. In-depth studies validated that the URB-597 administration reversed the positive effects of SCL on depressive-like behavior and anti-apoptosis. Similarly, URB-597 counteracted AEA levels reduced by SCL and decreased 2-AG levels. Furthermore, AM630 supplementation antagonized SCL's effect of improving IBI by reactivating the MAPK/NF-κB inflammation pathway. CONCLUSION: Overall, SCL, in collaboration with the endogenous cannabinoid system regulated by SCL, alleviates depression associated IBI. The specific mechanism involes SCL decreasing AEA levels to inhibit colon tissue cell apoptosis by up-regulating FAAH. Simultaneously, it directly triggers CB2R to reduce inflammation responses, further alleviating IBI.

Epigenetic modifications of inflammation in spinal cord injury.

Spinal cord injury (SCI) is a central nervous system injury that leads to neurological dysfunction or paralysis, which seriously affects patients' quality of life and causes a heavy social and economic burden. The pathological mechanism of SCI has not been fully revealed, resulting in unsatisfactory clinical treatment. Therefore, more research is urgently needed to reveal its precise pathological mechanism. Numerous studies have shown that inflammation is closely related to various pathological processes in SCI. Inflammatory response is an important pathological process leading to secondary injury, and sustained inflammatory response can exacerbate the injury and hinder the recovery of neurological function after injury. Epigenetic modification is considered to be an important regulatory mechanism in the pathological process of many diseases. Epigenetic modification mainly affects the function and characteristics of genes through the reversibility of mechanisms such as DNA methylation, histone modification, and regulation of non-coding RNA, thus having a significant impact on the pathological process of diseases and the survival state of the body. Recently, the role of epigenetic modification in the inflammatory response of SCI has gradually entered the field of view of researchers, and epigenetic modification may be a potential means to treat SCI. In this paper, we review the effects and mechanisms of different types of epigenetic modifications (including histone modifications, DNA methylation, and non-coding RNAs) on post-SCI inflammation and their potential therapeutic effects on inflammation to improve our understanding of the secondary SCI stage. This review aims to help identify new markers, signaling pathways and targeted drugs, and provide theoretical basis and new strategies for the diagnosis and treatment of SCI.

Psychological intervention based on social cognitive theory: Treating pain, anxiety, and depression in perioperative patients.

BACKGROUND: Surgery is an effective method for treating certain diseases. Factors such as disease, preoperative fear and tension, surgical stress, postoperative pain, and related complications directly affect the smooth progression and outcome of surgery. Patients may experience a series of psychological and physiological changes during the perioperative period, resulting in anxiety and depression, which may reduce the pain threshold and worsen their prognosis. AIM: To investigate the effects of a psychological intervention among perioperative patients, based on social cognitive theory (SCT). METHODS: We enrolled 200 patients who underwent surgical care at The First People's Hospital of Lin'an District, Hangzhou between January and December 2023. They were categorized into a routine intervention group (n = 103) and a psychological intervention group (n = 97), based on the intervention strategies used. Various assessment tools, including the self-rating anxiety scale (SAS), the self-rating depression scale (SDS), and the Connor-Davidson Resilience scale, were used to measure patients' negative states and emotions. The pre- and post-intervention scores for these metrics in the two groups were then analyzed. RESULTS: In the psychological intervention group, the SAS and SDS scores (31.56 ± 5.18 and 31.46 ± 4.57, respectively) were significantly reduced compared to the routine intervention group (P < 0.05). The visual analog scale pain scores at 12 and 24 hours after intervention (6.85 ± 1.21, 4.24 ± 0.72) were notably higher than those in the routine intervention group (P < 0.05). The psychological intervention group also demonstrated superior scores in perseverance (36.08 ± 3.29), self-reliance (22.63 ± 2.91), optimism (11.42 ± 1.98), and resilience (70.13 ± 5.37), compared to the routine intervention group (P < 0.05). Additionally, the psychological intervention group's confrontation score (23.16 ± 4.29) was higher (P < 0.05). This group also reported lower scores in avoidance (9.28 ± 1.94) and yielding (6.19 ± 1.92) (P < 0.05). Lastly, the Short Form 36 Health Survey scores were significantly higher in the psychological intervention group, indicating a better quality of life (P < 0.05). CONCLUSION: Psychological intervention measures based on SCT can effectively alleviate pain, anxiety, and depression in perioperative patients.

Determinants of tree population temporal stability in a temperate mixed forest over a gradient of nitrogen addition.

Nitrogen (N) deposition is a significant threat to the functioning of forests and negatively impacts the delivery of forest goods and services. Contemporary management approaches seek to adapt forests to such N-deposition stressors, but to date how plant populations in natural forests respond to N deposition and what factors determine the contrasting responses among populations are still unclear. Here, we investigated the impact of N-addition (control: 0 kg ha-1 yr-1; low: 25 kg ha-1 yr-1; medium: 50 kg ha-1 yr-1; high: 75 kg ha-1 ha yr-1) on tree population temporal stability and how initial tree size, mycorrhizal type, and leaf N content (LNC; as a surrogate for functional trait composition) mediate tree population responses to N-addition in a Korean pine and mixed broadleaved dominated temperate forest in northern China. We quantified tree species population temporal stability as the ratio of mean to standard deviation of the year-by-year stem increments recorded in individual trees from 2015 to 2022 experimental period. The results showed different temporal stabilities of tree species among four N-addition levels, with the highest population stability observed within the high N-addition plots. Furthermore, initial tree size had significantly (p < 0.001) positive effects on population temporal stability. The effect of LNC and initial tree size were also contingent on the level of N applied. Specifically, increase in tree population LNC reduced population temporal stability in all plots where N was added. Our results imply that retention of large-sized trees and species with resource-conservative strategies (e.g., low LNC) could enhance forest stability under N deposition.

Wogonin protects against bleomycin-induced mouse pulmonary fibrosis via the inhibition of CDK9/p53-mediated cell senescence.

Pulmonary fibrosis (PF) is a fatal interstitial lung disease associated with declining pulmonary function but currently with few effective drugs. Cellular senescence has been implicated in the pathogenesis of PF and could be a potential therapeutic target. Emerging evidence suggests wogonin, the bioactive compound isolated from Scutellaria baicalensis, owns the anti-senescence properties, however, the possible impact of wogonin on PF and the potential mechanisms remain unclear. In this study, a well-established mouse model of PF was utilized which mice were administrated with bleomycin (BLM). Strikingly, wogonin treatment significantly reduced fibrosis deposition in the lung induced by BLM. In vitro, wogonin also suppressed fibrotic markers of cultured epithelial cells stimulated by BLM or hydrogen peroxide. Mechanistic investigation revealed that wogonin attenuated the expressions of DNA damage marker γ-H2AX and senescence-related markers including phosphorylated p53, p21, retinoblastoma protein (pRB), and senescence-associated ß-galactosidase (SA-ß-gal). Moreover, wogonin, as a direct and selective inhibitor of cyclin-dependent kinase 9 (CDK9), exhibited anti-fibrotic capacity by inhibiting CDK9 and p53/p21 signalling. In conclusion, wogonin protects against BLM-induced PF in mice through the inhibition of cell senescence via the regulation of CDK9/p53 and DNA damage pathway. This is the first study to demonstrate the beneficial effect of wogonin on PF, and its implication as a novel candidate for PF therapy.

Machine learning-based autophagy-related prognostic signature for personalized risk stratification and therapeutic approaches in bladder cancer.

OBJECTIVE: Bladder cancer (BCa) is a highly lethal urological malignancy characterized by its notable histological heterogeneity. Autophagy has swiftly emerged as a diagnostic and prognostic biomarker in diverse cancer types. Nonetheless, the currently accessible autophagy-related signature specific to BCa remains limited. METHODS: A refined autophagy-related signature was developed through a 10-fold cross-validation framework, incorporating 101 combinations of machine learning algorithms. The performance of this signature in predicting prognosis and response to immunotherapy was thoroughly evaluated, along with an exploration of potential drug targets and compounds. In vitro and in vivo experiments were conducted to verify the regulatory mechanism of hub gene. RESULTS: The autophagy-related prognostic signature (ARPS) has exhibited superior performance in predicting the prognosis of BCa compared to the majority of clinical features and other developed markers. Higher ARPS is associated with poorer prognosis and reduced sensitivity to immunotherapy. Four potential targets and five therapeutic agents were screened for patients in the high-ARPS group. In vitro and vivo experiments have confirmed that FKBP9 promotes the proliferation, invasion, and metastasis of BCa. CONCLUSIONS: Overall, our study developed a valuable tool to optimize risk stratification and decision-making for BCa patients.

Magnetic resonance imaging-based radiomics nomogram for the evaluation of therapeutic responses to neoadjuvant chemohormonal therapy in high-risk non-metastatic prostate cancer.

PURPOSE: The aim of this study was to assess the potential application of a radiomics features-based nomogram for predicting therapeutic responses to neoadjuvant chemohormonal therapy (NCHT) in patients with high-risk non-metastatic prostate cancer (PCa). METHODS: Clinicopathologic information was retrospectively collected from 162 patients with high-risk non-metastatic PCa receiving NCHT and radical prostatectomy at our center. The postoperative pathological findings were used as the gold standard for evaluating the efficacy of NCHT. The least absolute shrinkage and selection operator (LASSO) was conducted to develop radiomics signature. Multivariate logistic regression analyses were conducted to identify the predictors of a positive pathological response to NCHT, and a nomogram was constructed based on these predictors. RESULTS: Sixty-three patients (38.89%) experienced positive pathological response to NCHT. Receiver operating characteristic analyses showed that the area under the curve (AUC) of periprostatic fat (PPF) radiomics signature was 0.835 (95% CI, 0.754-0.898), while the AUC of intratumoral radiomics signature was 0.822 (95% CI, 0.739-0.888). Multivariate logistic regression analysis revealed that PSA level, PPF radiomics signature and intratumoral radiomics signature were independent predictors of positive pathological response. A nomogram based on these three predictors was constructed. The AUC was 0.908 (95% CI, 0.839-0.954). The Hosmer-Lemeshow goodness-of-fit test showed that the nomogram was well calibrated. Decision curve analysis revealed the favorable clinical practicability of the nomogram. The nomogram was successfully validated in the validation cohort. Kaplan-Meier analyses showed that nomogram and positive pathological response were significantly related with survival of PCa. CONCLUSION: The radiomics-clinical nomogram based on mpMRI radiomics features exhibited superior predictive ability for positive pathological response to NCHT in high-risk non-metastatic PCa.

Environmental explanation of prostate cancer progression based on the comprehensive analysis of polychlorinated biphenyls.

OBJECTIVE: Polychlorinated biphenyls (PCBs) have caused great environmental concerns. The study aims to investigate underlying molecular mechanisms between PCBs exposure and prostate cancer (PCa). METHODS: To investigate the association between PCBs exposure and prostate cancer by using CTD, TCGA, and GEO datasets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to explore pathways associated with PCBs-related genes (PRGs). Using Lasso regression analysis, a novel PCBs-related prognostic model was developed. Both internal and external validations were conducted to assess the model's validity. Molecular docking was utilized to assess the binding capacity of PCBs to crucial genes. At last, preliminary experimental validations were conducted to confirm the biological roles of Aroclor 1254 in PCa cells. RESULTS: The GO enrichment analysis of PRGs revealed that the biological processes were most enriched in the regulation of transcription from the RNA polymerase II promoter and signal transduction. The KEGG enrichment analysis showed that of the pathways in cancer is the most significantly enriched. Next, a PCBs-related model was constructed. In the training, test, GSE70770, and GSE116918 cohorts, the biochemical recurrences free survival of the patients with high-risk scores was considerably lower. The AUCs at 5 years were 0.691, 0.718, 0.714, and 0.672 in the four cohorts, demonstrating the modest predictive ability. A nomogram that incorporated clinical characteristics was constructed. The results of the anti-cancer drug sensitivity analysis show chemotherapy might be more beneficial for patients at low risk. The molecular docking analysis demonstrated PCBs' ability to bind to crucial genes. PCa cells exposed to Aroclor 1254 at a concentration of 1 µM showed increased proliferation and invasion capabilities. CONCLUSIONS: This study provides new insights into the function of PCBs in PCa and accentuates the need for deeper exploration into the mechanistic links between PCBs exposure and PCa progression.

Preservation of Pulp Vitality in Type IIIA Dens Invaginatus with an Extensive Peri-invagination Lesion: a case Report with 5-year Follow-up.

Dens invaginatus may be associated with peri-invagination lesions and vital pulp concurrently. This case report examines the successful preservation of vital pulp and minimally invasive treatment of invagination for Oehlers type IIIA dens invaginatus with an extensive peri-invagination lesion. A healthy 19-year-old man presented with occasional swelling of the left maxillary anterior region. Pulp vitality tests revealed vital and healthy tooth pulp. CBCT indicated Oehlers type IIIA dens invaginatus with an invagination parallel to the pulp cavity. The diagnosis was type IIIA dens invaginatus with a peri-invagination lesion. The treatment plans involved preservation of the vital pulp and minimally invasive treatment of the invagination. A 5-year follow-up revealed that both healing of the peri-invagination lesion and preservation of the vital pulp had been successful. Pulp vitality can be preserved in type IIIA dens invaginatus associated with a peri-invagination lesion through minimally invasive treatment of the invagination.

[Mechanism of salidroside in inhibiting proliferation, migration and promoting phenotypic switching of arterial smooth muscle cells].

This study aims to examine the effect of salidroside(SAL) on the phenotypic switching of human aortic smooth muscle cells(HASMC) induced by the platelet-derived growth factor-BB(PDGF-BB) and investigate the pharmacological mechanism. Firstly, the safe concentration of SAL was screened by the lactate dehydrogenase release assay. HASMC were divided into control, model, and SAL groups, and the cells in other groups except the control group were treated with PDGF-BB for the modeling of phenotypic switching. Cell proliferation and migration were detected by the cell-counting kit(CCK-8) assay and Transwell assay, respectively. The cytoskeletal structure was observed by F-actin staining with fluorescently labeled phalloidine. The protein levels of proliferating cell nuclear antigen(PCNA), migration-related protein matrix metalloprotein 9(MMP-9), fibronectin, α-smooth muscle actin(α-SMA), and osteopontin(OPN) were determined by Western blot. To further investigate the pharmacological mechanism of SAL, this study determined the expression of protein kinase B(Akt) and mammalian target of rapamycin(mTOR), as well as the upstream proteins phosphatase and tensin homologue(PTEN) and platelet-derived growth factor receptor ß(PDGFR-ß) and the downstream protein hypoxia-inducible factor-1α(HIF-1α) of the Akt/mTOR signaling pathway. The results showed that the HASMCs in the model group presented significantly increased proliferation and migration, the switching from a contractile phenotype to a secretory phenotype, and cytoskeletal disarrangement. Compared with the model group, SAL weakened the proliferation and migration of HASMC, promoted the expression of α-SMA(a contractile phenotype marker), inhibited the expression of OPN(a secretory phenotype marker), and repaired the cytoskeletal disarrangement. Furthermore, compared with the control group, the modeling up-regulated the levels of phosphorylated Akt and mTOR and the relative expression of PTEN, HIF-1α, and PDGFR-ß. Compared with the model group, SAL down-regulated the protein levels of phosphorylated Akt and mTOR, PTEN, PDGFR-ß, and HIF-1α. In conclusion, SAL exerts a protective effect on the HASMCs exposed to PDGF-BB by regulating the PDGFR-ß/Akt/mTOR/HIF-1α signaling pathway.

Expedited liver transplantation as first-line therapy for severe alcohol hepatitis: ELFSAH; deferring corticosteroids in the sickest subset of patients.

BACKGROUND & AIMS: Severe alcohol-associated hepatitis (SAH) represents a lethal subset of alcohol-associated liver disease. Although corticosteroids are recommended by guidelines, their efficacy and safety remain questionable and so liver transplantation (LT) has been increasingly utilized. The timing and indication of corticosteroid use, specifically in patients being considered for LT requires further clarification. METHODS: A retrospective analysis was conducted on 256 patients with SAH between 2018 and 2022 at a single US center. RESULTS: Twenty of these patients underwent LT. Of the 256 patients, 38% had what we termed "catastrophic" SAH, defined as a MELD-Na ≥35 and/or discriminant function (DF) ≥100, which carried a mortality of 90% without LT. Compared with 100 matched controls, patients undergoing LT exhibited a one-year survival rate of 100% versus 35% (p < .0005). LT provided an absolute risk reduction of 65%, with a number needed to treat of 1.5. Steroid utilization in the entire cohort was 19% with 60% developing severe complications. Patients administered steroids were younger with lower MELD and DF scores. Only 10% of those prescribed steroids derived a favorable response. Sustained alcohol use post-LT was 20%. CONCLUSIONS: We propose ELFSAH: Expedited LT as First Line Therapy for SAH; challenging the current paradigm with recommendations to defer steroids in patients with "catastrophic" SAH (defined as: MELD-Na ≥35 and/or DF ≥100). Patients should be seen urgently by hepatology, transplant surgery, psychiatry and social work. Patients without an absolute contraindication should be referred for LT as first-line therapy during their index admission.

Prognostic significance of the novel immunonutritional marker of cholesterol-to-lymphocyte ratio in patients with non-metastatic breast cancer.

BACKGROUND: Although there is a strong correlation between the novel cholesterol-to-lymphocyte ratio (CLR) and tumor survival, its prognostic significance in breast cancer (BC) is unknown. After analyzing the relationship between CLR and the overall survival (OS) of patients with BC, we created a predictive model. METHODS: Following retrospective enrollment, 1316 patients with BC were randomized into two cohorts: validation (n = 392) and training (n = 924). Distinct factors within the training dataset were identified for OS by univariate and multivariate Cox analyses; two-tailed P-value < 0.05 were considered to indicate statistical significance. On this premise, we developed novel signals for survival prediction and utilized the calibration curve, receiver operating characteristic curves, and concordance index (C-index) to validate their efficacy across both datasets. RESULTS: Patients with BC were categorized into two categories with differing prognoses based on the CLR score [hazard ratio = 0.492; 95% confidence interval (CI): 0.286-0.846, P = 0.009]. A prediction nomogram was created based on multivariate analysis, which showed that N stage, postoperative pathological categorization, and CLR score were all independently correlated with OS. In the training [C-index = 0.831 (95% CI: 0.788-0.874)] and validation [C-index = 0.775 (95% CI: 0.694-0.856)] cohorts, the nomogram demonstrated favorable performance in predicting OS. In both the training and validation cohorts, it outperformed the traditional staging system [C-index = 0.702 (95% CI: 0.623-0.782)] and [C-index = 0.709 (95% CI: 0.570-0.847)]. The accurate prediction by the signature was further demonstrated by the time-dependent receiver operating characteristic curves. CONCLUSIONS: The novel immunonutritional marker CLR could function as a simplified, cost-effective, easily accessible, non-invasive, and readily promotive prognostic indicator for patients with early-stage BC and demonstrates superior predictive power than the traditional staging system.

In Vitro Propagation Technology for the Endangered Aquatic Species Nymphoides coronata.

Nymphoides coronata is an endangered aquatic plant species with significant medicinal and ecological importance. To preserve N. coronata from going extinct, we need to provide seedlings and efficient multiplication techniques so that it can be extensively studied. This study aimed to identify the most suitable sterilization treatment, growth medium, and substrate for the cultivation and propagation of N. coronata. Ethanol sterilization, fungicide treatment, and sterile water washing were the most important sterilization steps. A combination of 6-benzylaminopurine (6-BA) and indoleacetic acid (IAA) was the most suitable medium for bud induction and shoot proliferation. The use of α-naphthaleneacetic acid (NAA) increased the rooting rate and rooting time compared to indole-3-butyric acid (IBA). Increasing the concentration of NAA from 0.5 to 1.0 mg/L increased the rooting rate from 78 to 100% and reduced the rooting time from 7 to 5 days. The survival rate of N. coronata seedlings was 100% in a mixture of red soil and sand (1:1, w/w). As a result, the procedure mentioned above could potentially be used to safely propagate this rare species on a large scale. These findings provide valuable insights into the optimal conditions for the successful cultivation and propagation of N. coronata, which can contribute to the conservation and sustainable use of this important rare plant species.

Disturbance history, neighborhood crowding and soil conditions jointly shape tree growth in temperate forests.

Understanding how different mechanisms act and interact in shaping communities and ecosystems is essential to better predict their future with global change. Disturbance legacy, abiotic conditions, and biotic interactions can simultaneously influence tree growth, but it remains unclear what are their relative contributions and whether they have additive or interactive effects. We examined the separate and joint effects of disturbance intensity, soil conditions, and neighborhood crowding on tree growth in 10 temperate forests in northeast China. We found that disturbance was the strongest driver of tree growth, followed by neighbors and soil. Specifically, trees grew slower with decreasing initial disturbance intensity, but with increasing neighborhood crowding, soil pH and soil total phosphorus. Interestingly, the decrease in tree growth with increasing soil pH and soil phosphorus was steeper with high initial disturbance intensity. Testing the role of species traits, we showed that fast-growing species exhibited greater maximum tree size, but lower wood density and specific leaf area. Species with lower wood density grew faster with increasing initial disturbance intensity, while species with higher specific leaf area suffered less from neighbors in areas with high initial disturbance intensity. Our study suggests that accounting for both individual and interactive effects of multiple drivers is crucial to better predict forest dynamics.

Expert consensus on endodontic therapy for patients with systemic conditions.

The overall health condition of patients significantly affects the diagnosis, treatment, and prognosis of endodontic diseases. A systemic consideration of the patient's overall health along with oral conditions holds the utmost importance in determining the necessity and feasibility of endodontic therapy, as well as selecting appropriate therapeutic approaches. This expert consensus is a collaborative effort by specialists from endodontics and clinical physicians across the nation based on the current clinical evidence, aiming to provide general guidance on clinical procedures, improve patient safety and enhance clinical outcomes of endodontic therapy in patients with compromised overall health.

Scorpiones, Scolopendra and Gekko Inhibit Lung Cancer Growth and Metastasis by Ameliorating Hypoxic Tumor Microenvironment via PI3K/AKT/mTOR/HIF-1α Signaling Pathway.

OBJECTIVE: To investigate whether Buthus martensii karsch (Scorpiones), Scolopendra subspinipes mutilans L. Koch (Scolopendra) and Gekko gecko Linnaeus (Gekko) could ameliorate the hypoxic tumor microenvironment and inhibit lung cancer growth and metastasis by regulating phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin/hypoxia-inducible factor-1α (PI3K/AKT/mTOR/HIF-1α) signaling pathway. METHODS: Male C57BL/6J mice were inoculated with luciferase labeled LL/2-luc-M38 cell suspension to develop lung cancer models, with rapamycin and cyclophosphamide as positive controls. Carboxy methyl cellulose solutions of Scorpiones, Scolopendra and Gekko were administered intragastrically as 0.33, 0.33, and 0.83 g/kg, respectively once daily for 21 days. Fluorescent expression were detected every 7 days after inoculation, and tumor growth curves were plotted. Immunohistochemistry was performed to determine CD31 and HIF-1α expressions in tumor tissue and microvessel density (MVD) was analyzed. Western blot was performed to detect the expression of PI3K/AKT/mTOR/HIF-1α signaling pathway-related proteins. Enzyme-linked immunosorbent assay was performed to detect serum basic fibroblast growth factor (bFGF), transforming growth factor-ß1 (TGF-ß1) and vascular endothelial growth factor (VEGF) in mice. RESULTS: Scorpiones, Scolopendra and Gekko prolonged the survival time and inhibited lung cancer metastasis and expression of HIF-1α (all P<0.01). Moreover, Scorpiones, Scolopendra and Gekko inhibited the phosphorylation of AKT and ribosomal protein S6 kinase (p70S6K) (P<0.05 or P<0.01). In addition, they also decreased the expression of CD31, MVD, bFGF, TGF-ß1 and VEGF compared with the model group (P<0.05 or P<0.01). CONCLUSION: Scorpiones, Scolopendra and Gekko all showed beneficial effects on lung cancer by ameliorating the hypoxic tumor microenvironment via PI3K/AKT/mTOR/HIF-1α signaling pathway.

Pt1.8Pd0.2CuGa Intermetallic Nanocatalysts with Enhanced Methanol Oxidation Performance for Efficient Hybrid Seawater Electrolysis.

Seawater electrolysis is a potentially cost-effective approach to green hydrogen production, but it currently faces substantial challenges for its high energy consumption and the interference of chlorine evolution reaction (ClER). Replacing the energy-demanding oxygen evolution reaction with methanol oxidation reaction (MOR) represents a promising alternative, as MOR occurs at a significantly low anodic potential, which cannot only reduce the voltage needed for electrolysis but also completely circumvents ClER. To this end, developing high-performance MOR catalysts is a key. Herein, a novel quaternary Pt1.8Pd0.2CuGa/C intermetallic nanoparticle (i-NP) catalyst is reported, which shows a high mass activity (11.13 A mgPGM -1), a large specific activity (18.13 mA cmPGM -2), and outstanding stability toward alkaline MOR. Advanced characterization and density functional theory calculations reveal that the introduction of atomically distributed Pd in Pt2CuGa intermetallic markedly promotes the oxidation of key reaction intermediates by enriching electron concentration around Pt sites, resulting in weak adsorption of carbon-containing intermediates and favorable adsorption of synergistic OH- groups near Pd sites. MOR-assisted seawater electrolysis is demonstrated, which continuously operates under 1.23 V for 240 h in simulated seawater and 120 h in natural seawater without notable degradation.

Blasting profile evaluation of sand-mud interbedded surrounding rock during the large-span tunnel construction.

The sand-mud interbedded surrounding rock contains discontinuities, such as horizontal bedding, joints, weak planes and weak interlayers. Drilling and blasting construction in this kind of surrounding rock is very likely to cause very serious over-/under-excavation phenomenon and excessive damage to surrounding rock, and the contour flatness after smooth blasting of the tunnel is also difficult to be guaranteed, which increases subsequent construction procedures and reduces production efficiency. In order to effectively evaluate the smooth blasting effect of the sand-mud interbedded surrounding rock tunnel, taking a tunnel project in southwest China as the research background, the blasting numerical simulation of the sand-mud interbedded surrounding rock tunnel was carried out using the dynamic analysis program, and the corresponding blasting optimization scheme was obtained. Subsequently, based on fuzzy mathematical theory, the evaluation system of blasting effect of sand-mud interbedded tunnel was established by combining the evaluation criteria of tunnel smooth blasting quality. Immediately afterwards, the weights of each influencing factor index were determined, and the blasting shaping effect of the original blasting scheme and the optimized blasting scheme was evaluated. Finally, the results have shown that the optimized tunnel blasting profile effect was better than the original blasting scheme. The corresponding research results have certain guiding significance for similar tunnel blasting effect evaluation and blasting parameter design.