Leafhopper salivary carboxylesterase suppresses JA-Ile synthesis to facilitate initial arbovirus transmission in rice phloem.

Plant jasmonoyl-L-isoleucine (JA-Ile) is a major defense signal against insect feeding, but whether or how insect salivary effectors suppress JA-Ile synthesis and thus facilitate viral transmission in plant phloem remains elusive. Insect carboxylesterases (CarEs) are the third major family of detoxification enzymes. Here, we identify a new leafhopper CarE10 that specifically expressed in salivary glands and is secreted into rice phloem as the saliva component. Leafhopper CarE10 directly binds and promotes rice Jasmonate resistant 1 (JAR1) degradation by the proteasome system. Moreover, the direct association of CarE10 with JAR1 obviously impairs JAR1 enzyme activity for JA conversion to JA-Ile in in-vitro JA-Ile synthesis system. A devastating rice reovirus activates and promotes co-secretion of virions and CarE10 by virus-induced vesicles into saliva-stored salivary cavities of leafhopper vectors and ultimately into rice phloem to establish initial infection. Furthermore, virus-mediated increase of CarE10 secretion or overexpression of CarE10 in transgenic rice plants causes the reduced levels of JAR1 and thus suppresses JA-Ile synthesis, thereby promoting host attractiveness to insect vectors and facilitating initial viral transmission. Our findings provide insights into how insect salivary protein CarE10 suppresses host JA-Ile synthesis to benefit initial virus transmission in rice phloem.

LC3-dependent extracellular vesicles promote M-MDSC accumulation and immunosuppression in colorectal cancer.

For a long time, myeloid-derived suppressor cells (MDSCs) dilated in circulation system of colorectal cancer (CRC) patients have been puzzling clinicians. Various evidence shows that MDSCs constitute the bulk of immunosuppression in CRC, which is related to tumor growth, adhesion, invasion, metastasis, and immune escape. However, the mechanisms underlying these cells formation remain incompletely understood. In this study, we reported that CRC cell-derived LC3-dependent extracellular vesicles (LDEVs)-mediated M-MDSCs formation via TLR2-MYD88 pathway. Furthermore Hsp60 was the LDEVs surface ligand that triggered these MDSCs induction. In clinical studies, we reported that accumulation of circulating M-MDSCs as well as IL-10 and arginase1 secretion were reliant upon the levels of tumor cell-derived LDEVs in CRC patients. These findings indicated how local tumor cell-derived extracellular vesicles influence distal hematopoiesis and provided novel justification for therapeutic targeting of LDEVs in patients with CRC.

Brain extended and closed forms glutathione levels decrease with age and extended glutathione is associated with visuospatial memory.

During aging, the brain is subject to greater oxidative stress (OS), which is thought to play a critical role in cognitive impairment. Glutathione (GSH), as a major antioxidant in the brain, can be used to combat OS. However, how brain GSH levels vary with age and their associations with cognitive function is unclear. In this study, we combined point-resolved spectroscopy and edited spectroscopy sequences to investigate extended and closed forms GSH levels in the anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), and occipital cortex (OC) of 276 healthy participants (extended form, 166 females, age range 20-70 years) and 15 healthy participants (closed form, 7 females, age range 26-56 years), and examined their relationships with age and cognitive function. The results revealed decreased extended form GSH levels with age in the PCC among 276 participants. Notably, the timecourse of extended form GSH level changes in the PCC and ACC differed between males and females. Additionally, positive correlations were observed between extended form GSH levels in the PCC and OC and visuospatial memory. Additionally, a decreased trend of closed form GSH levels with age was also observed in the PCC among 15 participants. Taken together, these findings enhance our understanding of the brain both closed and extended form GSH time course during normal aging and associations with sex and memory, which is an essential first step for understanding the neurochemical underpinnings of healthy aging.

Soil microorganisms play an important role in the detrimental impact of biodegradable microplastics on plants.

Biodegradable plastics were developed to mitigate environmental pollution caused by conventional plastics. Research indicates that biodegradable microplastics still have effects on plants and microorganisms as their non-biodegradable counterparts, yet the effects on vegetable crops are not well-documented. Additionally, the function of soil microorganisms affected by biodegradable microplastics on the fate of microplastics remains unverified. In this study, Brassica chinensis was cultivated in soil previously incubated for one year with low-density polyethylene (LDPE-MPs) and poly (butylene adipate-co-terephthalate) microplastics (PBAT-MPs) at 0.05 % and 2 % concentrations. High concentrations of PBAT-MPs significantly reduced the biomass to 5.83 % of the control. The abundance of Methyloversatilis, IS-44, and UTCFX1 in the rhizosphere bacterial community increased significantly in the presence of PBAT-MPs. Moreover, these microplastics significantly enhanced soil enzyme activity. Incubation tests were performed with three PBAT plastic sheets to assess the function of the altered bacterial community in the soil of control (Control-soil) and soil treated with high concentrations of PBAT-MPs (PBAT-MPs-soil). Scanning Electron Microscopy and Atomic Transfer Microscopy (SEM/ATM) results confirmed enhanced PBAT degradation in the PBAT-MPs-soil. PICRUST2 analysis revealed that pathways related to substance degradation were upregulated in the PBAT-MPs-soil. Furthermore, a higher percentage of strains with PBAT-MPs-degrading ability was found in PBAT-MPs-soil. Our results confirm that PBAT-MPs significantly inhibit the growth of vegetable crops and that soil bacterial communities affected by PBAT-MPs are instrumental in degrading them.

Association of the Stability Ratio With Postoperative Clinical Function and Recurrence of Instability in Patients With Anterior Shoulder Instability: A Retrospective Cohort Study.

Background: The stability ratio (SR) is used to assess the stability of the glenoid in anterior shoulder instability (ASI). However, the association between the SR and postoperative clinical function and instability recurrence after arthroscopic Bankart repair is unknown. Hypothesis: Patients with a higher SR would have better postoperative clinical scores and a lower incidence of recurrent instability than patients with a lower SR after arthroscopic Bankart repair. Study Design: Cohort study; Level of evidence, 3. Methods: A total of 62 patients who underwent arthroscopic Bankart repair for ASI between 2013 and 2019 were enrolled. All patients had at least 2 years of follow-up data. The preoperative SR was calculated via biomechanical testing based on patient-specific 3-dimensional glenoid models, and patients were evenly divided into 2 groups: high SR (≥16.13%) and low SR (<16.13%). Baseline information (patient characteristics, clinical history, bone defect area [BDA], and SR), clinical scores at the final follow-up (Single Assessment Numerical Evaluation, Western Ontario Shoulder Index, and American Shoulder and Elbow Surgeons), and instability recurrence were compared between the 2 groups. Results: No significant differences were found in the baseline information between the high- and low-SR groups, except for the BDA (8.5% [high-SR group] vs 11.9% [low-SR group]; P = .01). No patients in the high-SR group had recurrent instability, while 6 patients (19.4%) had recurrent instability in the low-SR group (P = .02). Patients in the high-SR group had superior clinical outcomes compared with those in the low-SR group in terms of postoperative Western Ontario Shoulder Index scores (median, 205 vs 410, respectively; P = .006) and American Shoulder and Elbow Surgeons scores (median, 98.3 vs 95, respectively; P = .02). Conclusion: In the present study, the SR was significantly associated with postoperative clinical function and recurrence of instability after arthroscopic Bankart repair in patients with ASI.

NF-κB affected the serum levels of TNF-α and IL-1ß via activation of the MAPK/NF-κB signaling pathway in rat model of acute pulmonary microthromboembolism.

Pulmonary thromboembolism caused by thrombi blocking major pulmonary artery and its branches, is a frequently encountered phenomenon and an important cause of high morbidity and mortality in lung diseases and may develop into persistent pulmonary hypertension (PH). Nuclear factor-κB (NF-κB) signaling pathway had been reported participated in the formation and development of PH by promoting inflammatory response. The aim of this study was to investigate the effects of NF-κB activation on the serum levels of tumor necrosis factor α (TNF-α) and interleukin-1ß (IL-1ß) in acute pulmonary microthromboembolism (APMTE) rats. Rats were randomized into five groups. APMTE group received jugular vein injection of autologous thrombus, while control group rats received normal saline injection. Pulmonary hemodynamic parameters were measured through ECHO-guided transthoracic puncture. Pulmonary vascular morphological changes were analyzed by HE. The expression changes of NF-κB and serum TNF-α、IL-1ß levels were detected by enzyme-linked immunosorbent assay. Protein expression of the MAPK/NF-κB signaling pathway including p-IκBα, p-p38 MAPK, p-NF-κB p65, IκBα, p38 MAPK, and NF-κB p65 was determined using western blot analysis. Compared with control group, the expression of NF-κB in lung tissue and the levels of serum TNF-α and IL-1ß rats were higher, a significant reduction in IκBα and elevation in the phosphorylation of IκBα, p38 MAPK, and NF-κB p65 were found in APMTE group rats. And UK administration reversed the APMTE-induced increase in TNF-α, IL-1ß, p-IκBα, p-MAPK, and p-NF-κB protein. Furthermore, the levels of NF-κB, TNF-α, and IL-1ß were positively correlated with mean pulmonary artery. And the levels of TNF-α and IL-1ß were positively correlated with NF-κB. These findings suggest that the activation of MAPK/NF-κB pathway as a critical driver of increasing TNF-α and IL-1ß level in APMTE rats and UK exerted protective effects against APMTE-induced PH may be related to the downregulation of the MAPK/NF-κB signaling pathway.

A dynamic prediction model of landslide displacement based on VMD-SSO-LSTM approach.

Addressing the limitations of existing landslide displacement prediction models in capturing the dynamic characteristics of data changes, this study introduces a novel dynamic displacement prediction model for landslides. The proposed method combines Variational Mode Decomposition (VMD) with Sparrow Search Optimization (SSO) and Long Short-Term Memory (LSTM) techniques to formulate a comprehensive VMD-SSO-LSTM model. Through the application of VMD, the method dissects cumulative displacement and rainfall data, thereby extracting distinct components such as trend, periodicity, and fluctuation components for displacement, as well as low-frequency and high-frequency components for rainfall. Furthermore, leveraging Gray Correlational Analysis, the interrelationships between the periodic component of displacement and the low-frequency component of rainfall, as well as the fluctuation component of displacement and the high-frequency component of rainfall, are established. Building upon this foundation, the SSO-LSTM model dynamically predicts the interrelated displacement components, synthesizing the predicted values of each component to generate real-time dynamic forecasts. Simulation results underscore the effectiveness of the proposed VMD-SSO-LSTM model, indicating root-mean-square error (RMSE) and mean absolute percentage error (MAPE) values of 1.2329 mm and 0.1624%, respectively, along with a goodness of fit (R2) of 0.9969. In comparison to both back propagation (BP) prediction model and LSTM prediction model, the VMD-SSO-LSTM model exhibits heightened predictive accuracy.

Diversity-Oriented Synthesis of Indole-Fused Polycyclic Scaffolds via Rhodium-Catalyzed NH-Indole-Directed C-H Coupling of 2-Phenyl-1H-indoles with Propargylic Alcohol Derivatives.

Diversity-oriented synthesis strategy for the efficient assembly of indole-fused polycyclic scaffolds via rhodium-catalyzed NH-indole-directed C-H coupling with propargylic alcohol derivatives in a regioselective manner was developed. Five 2-phenyl-1H-indole-embedded core skeletons were synthesized. In particular, three different indole-fused exo-olefin-containing polycycles were realized, which may be manipulated for further chemistry.

Association analysis between organophosphorus flame retardants exposure and the risk of depression: Data from NHANES 2017-2018.

BACKGROUND: Organophosphorus flame retardants (OPFRs) can damage the brain and may cause abnormal behaviors. There was no population-based study to reveal the relationship between OPFRs and the occurrence of depression. This study utilized a publicly available database to investigate the correlation between OPFRs exposure and the risk of depression, and the mediation effect of inflammation on the correlation. METHODS: Data in this study was from the database of the National Health and Nutrition Examination Survey. Multifactorial logistic regression was used to estimate the relationship between OPFRs exposure and the risk of depression, and a mediation effect model was constructed to explore the impact of inflammation on the correlation. RESULTS: Data of 1273 participants was included in the study. It was found that individuals with high urinary concentration of bis-(2-chloroethyl) phosphate had an increased risk of developing depression (OR = 1.217, 95 % CI: 1.032-1.435). Combined exposure to OPFRs was significantly associated with the increased risk of depression than single OPFRs exposure. Subgroup analyses based on inflammatory levels in the body revealed that inflammation might exert the mediation effect on the association between OPFRs exposure and the risk of depression, with the contribution proportion of 8.23 %. LIMITATIONS: Cross-sectional data and rapid metabolism of OPFRs lead to uncertainty in revealing long-term exposure in the body. CONCLUSIONS: There was a correlation between OPFRs exposure and the risk of depression, which may be mediated by inflammation in the body to some extent.

The LANCET robotic system can improve surgical efficiency in total hip arthroplasty: A prospective randomized, multicenter, parallel-controlled clinical trial.

Objective: To evaluate the accuracy and safety of the LANCET robotic system, a robot arm assisted operation system for total hip arthroplasty via a multicenter clinical randomized controlled trial. Methods: A total of 116 patients were randomized into two groups: LANCET robotic arm assisted THA group (N = 58) and the conventional THA group (N = 58). General information about the patients was collected preoperatively. Operational time and bleeding were recorded during the surgery. The position of the acetabular prosthesis was evaluated by radiographs one week after surgery and compared with preoperative planning. Harris score, hip mobility, prosthesis position and angle and complications were compared between the two groups at three months postoperatively. Results: None of the 111 patients who ultimately completed the 3-month follow-up experienced adverse events such as hip dislocation and infection during follow-up. In the RAA group, 52 (92.9 %) patients were located in the Lewinnek safe zone and 49 (87.5 %) patients were located in the Callanan safe zone. In the control group were 47 (85.5 %) and 44 (80.0 %) patients, respectively. In the RAA group, 53 (94.6 %) patients had a postoperative acetabular inclination angle and 51 (91.1 %) patients had an acetabular version angle within a deviation of 5° from the preoperative plan. These numbers were significantly higher than those of the control group, which consisted of 42 (76.4 %) and 34 (61.8 %) patients respectively. There were no significant differences between the two groups of subjects in terms of general condition, intraoperative bleeding, hip mobility, and adverse complications. Conclusion: The results of this prospective randomized, multicenter, parallel-controlled clinical study demonstrated that the LANCET robotic system leads conventional THA surgery in accuracy of acetabular cup placement and does not differ from conventional THA surgery in terms of postoperative hip functional recovery and complications. The translational potential of this article: In the past, the success rate of total hip arthroplasty (THA) relied heavily on the surgeon's experience. As a result, junior doctors needed extensive training to become proficient in this technique. However, the introduction of surgical robots has significantly improved this situation. By utilizing robotic assistance, both junior and senior doctors can perform THA quickly and efficiently. This advancement is crucial for the widespread adoption of THA, as patients can now receive surgical treatment in local facilities instead of overwhelming larger hospitals and straining medical resources. Moreover, the development of surgical robots with fully independent intellectual property rights holds immense value in overcoming the limitations of high-end medical equipment. This aligns with the objectives outlined in the 14th Five Year Plan for National Science and Technology Strategy.

Targeting bone homeostasis regulation: potential of traditional Chinese medicine flavonoids in the treatment of osteoporosis.

Osteoporosis is a systemic metabolic disease characterized by disrupted bone formation/resorption and homeostasis. Flavonoids extracted from traditional Chinese medicinal plants regulate bone homeostasis by intervening in differentiating bone marrow mesenchymal stem cells, balancing the bone immune system, inhibiting oxidative stress response, and reversing iron overload. The target molecules and signaling pathways, such as Wnt/ß-catenin and OPG/RANKL/RANK, directly affect osteoblast/osteoclast activity, exhibiting significant potential in the treatment of OP. Therefore, this study presents a systematic review of the recent literature to provide comprehensive information on the traditional Chinese medicine flavonoids involved in the regulation of bone homeostasis. Also, the molecular mechanisms and pharmacological uses of these metabolites are summarized, and their clinical translation and development potential are discussed.

Identification of Novel Cuproptosis-Related Genes Mediating the Prognosis and Immune Microenvironment in Cholangiocarcinoma.

BACKGROUND: Cuproptosis is a novel type of mediated cell death strongly associated with the progression of several cancers and has been implicated as a potential therapeutic target. However, the role of cuproptosis in cholangiocarcinoma for prognostic prediction, subgroup classification, and therapeutic strategies remains largely unknown. METHODS: A systematic analysis was conducted among 146 cuproptosis-related genes and clinical information based on independent mRNA and protein datasets to elucidate the potential mechanisms and prognostic prediction value of cuproptosis-related genes. A 10-cuproptosis-related gene prediction model was constructed, and its effects on cholangiocarcinoma prognosis were significantly connected to poor patient survival. Additionally, the expression patterns of our model included genes that were validated with several cholangiocarcinoma cancer cell lines and a normal biliary epithelial cell line. RESULTS: First, a 10-cuproptosis-related gene signature (ADAM9, ADAM17, ALB, AQP1, CDK1, MT2A, PAM, SOD3, STEAP3, and TMPRSS6) displayed excellent predictive performance for the overall survival of cholangiocarcinoma. The low-cuproptosis group had a significantly better prognosis than the high-cuproptosis group with transcriptome and protein cohorts. Second, compared with the high-risk and low-risk groups, the 2 groups displayed distinct tumor microenvironments, reduced proportions of endothelial cells, and increased levels of cancer-associated fibroblasts based on CIBERSORTx and EPIC analyses. Third, patients' sensitivities to chemotherapeutic drugs and immune checkpoints revealed distinctive differences between the 2 groups. Finally, in replicating the expression patterns of the 10 genes, these results were validated with quantitative real-time polymerase chain reaction results validating the abnormal expression pattern of the target genes in cholangiocarcinoma. CONCLUSIONS: Collectively, we established and verified an effective prognostic model that could separate cholangiocarcinoma patients into 2 heterogeneous cuproptosis subtypes based on the molecular or protein characteristics of 10 cuproptosis-related genes. These findings may provide potential benefits for unveiling molecular characteristics and defining subgroups could improve the early diagnosis and individualized treatment of cholangiocarcinoma patients.

Structural insights into human exon-defined spliceosome prior to activation.

Spliceosome is often assembled across an exon and undergoes rearrangement to span a neighboring intron. Most states of the intron-defined spliceosome have been structurally characterized. However, the structure of a fully assembled exon-defined spliceosome remains at large. During spliceosome assembly, the pre-catalytic state (B complex) is converted from its precursor (pre-B complex). Here we report atomic structures of the exon-defined human spliceosome in four sequential states: mature pre-B, late pre-B, early B, and mature B. In the previously unknown late pre-B state, U1 snRNP is already released but the remaining proteins are still in the pre-B state; unexpectedly, the RNAs are in the B state, with U6 snRNA forming a duplex with 5'-splice site and U5 snRNA recognizing the 3'-end of the exon. In the early and mature B complexes, the B-specific factors are stepwise recruited and specifically recognize the exon 3'-region. Our study reveals key insights into the assembly of the exon-defined spliceosomes and identifies mechanistic steps of the pre-B-to-B transition.

Hyperthermia improves gemcitabine sensitivity of pancreatic cancer cells by suppressing the EFNA4/ß-catenin axis and activating dCK.

Background: Previously, our investigations have underscored the potential of hyperthermia to improve the therapeutic efficacy of gemcitabine (GEM) in pancreatic cancer (PC). Nonetheless, the precise underlying mechanisms remain elusive. Methods: We engineered two GEM-resistant PC cell lines (BxPC-3/GEM and PANC-1/GEM) and treated them with GEM alongside hyperthermia. The impact of hyperthermia on the therapeutic potency of GEM was ascertained through MTT assay, assessment of the concentration of its active metabolite dFdCTP, and evaluation of deoxycytidine kinase (dCK) activity. Lentivirus-mediated dCK silencing was further employed to validate its involvement in mediating the GEM-sensitizing effect of hyperthermia. The mechanism underlying hyperthermia-mediated dCK activation was explored using bioinformatics analyses. The interplay between hyperthermia and the ephrin A4 (EFNA4)/ß-catenin/dCK axis was investigated, and their roles in GEM resistance was further explored via the establishment of xenograft tumor models in nude mice. Results: Hyperthermia restored dCK expression in GEM-resistant cell lines, concurrently enhancing GEM sensitivity and fostering DNA damage and cell death. These observed effects were negated by dCK silencing. Regarding the mechanism, hyperthermia activated dCK by downregulating EFNA4 expression and mitigating ß-catenin activation. Overexpression of EFNA4 activated the ß-catenin while suppressing dCK, thus diminishing cellular GEM sensitivity-a phenomenon remediated by the ß-catenin antagonist MSAB. Consistently, in vivo, hyperthermia augmented the therapeutic efficacy of GEM on xenograft tumors through modulation of the ephrin A4/ß-catenin/dCK axis. Conclusion: This study delineates the role of hyperthermia in enhancing GEM sensitivity of PC cells, primarily mediated through the suppression of the EFNA4/ß-catenin axis and activation of dCK.

Cardamom consumption may improve cardiovascular metabolic biomarkers in adults: A systematic review and meta-analysis of randomized controlled trials.

The bioactive compounds in cardamom have been found to enhance cardiovascular health by improving blood lipids and inflammation. We hypothesized that cardamom consumption might ameliorate cardiovascular metabolic biomarkers in adults; however, there is still debate regarding its impact on cardiac metabolism. This research was therefore designed to determine if cardamom consumption had a favorable impact on lipid profiles, inflammatory markers, and oxidative stress indices as they related to cardiovascular diseases. A comprehensive search was conducted through PubMed, Scopus, Embase, Web of Science, and the Cochrane Library on July 4, 2023. Using a random-effects model pooled the weighted mean difference (WMD) and 95% confidence interval (CI). The final 12 trials containing 989 participants were included. The results illustrated that cardamom consumption could improve total cholesterol (WMD = -8.56 mg/dL; 95% CI, -14.90 to -2.22), triglycerides (WMD = -14.09 mg/dL; 95% CI, -24.01 to -4.17), high-sensitivity C-reactive protein (WMD = -1.01 ng/mL; 95% CI, -1.81 to -0.22), and interleukin-6 (WMD = -1.81 pg/mL; 95% CI, -3.06 to -0.56). However, it did not have significant influences on high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and some indicators of oxidative stress. In conclusion, cardamom consumption can improve specific cardiovascular metabolic biomarkers and potentially confer protective effects on cardiovascular health. However, more large-scale clinical research with better designs would further validate the findings, which will offer substantial evidence of cardamom as nutritional and functional products.

Sclareol protected against intestinal barrier dysfunction ameliorating Crohn's disease-like colitis via Nrf2/NF-B/MLCK signalling.

BACKGROUND: Inflammation-induced intestinal barrier dysfunction is not only a pathological feature of Crohn's disease (CD) but also an important therapeutic target. Sclareol (SCL) is a nontoxic natural plant compound with anti-inflammatory effect, but its role in CD has not been established. METHODS: In vivo studies of mice with TNBS-induced colitis were carried out to evaluate the effects of SCL on CD-like colitis and intestinal barrier function. In vitro, a TNF-α-induced colonic organoid model was established to test the direct effect of SCL on inflammation-induced intestinal barrier injure and inflammatory response. The Nrf2/NF-κB/MLCK signalling was analysed to explore the mechanism of SCL. RESULTS: In vivo, SCL largely alleviated the colitis in TNBS mice, as evidenced by improvements in the weight loss, colitis symptoms, endoscopic score, macroscopic histological score, and histological inflammation score. Moreover, SCL significantly improved intestinal barrier dysfunction, manifested as reduced intestinal permeability and decreased intestinal bacterial translocation in TNBS mice. Importantly, SCL antagonised the intestinal mucosal inflammation while protecting tight junctions in TNBS mice. In vitro, SCL largely depressed pro-inflammatory cytokines levels and improved intestinal epithelial permeability in a TNF-α-induced colonic organoid model. In the context of CD, the protective effects of SCL against inflammation and intestinal barrier damage are at least partially results from the Nrf2 signalling activation and the NF-κB/MLCK signalling inhibition. CONCLUSIONS: SCL improved intestinal barrier dysfunction and alleviated CD-like colitis, possibly through modulation of Nrf2/NF-κB/MLCK signalling. In view of SCL's safety profile, there is hope that it will be useful in the clinic.

Predictive value of the Ranson and BISAP scoring systems for the severity and prognosis of acute pancreatitis: A systematic review and meta-analysis.

BACKGROUND: To systematically assess and compare the predictive value of the Ranson and Bedside Index of Severity in Acute Pancreatitis (BISAP) scoring systems for the severity and prognosis of acute pancreatitis (AP). METHODS: PubMed, Embase, Cochrane Library, and Web of Science were systematically searched until February 15, 2023. Outcomes in this analysis included severity and prognosis [mortality, organ failure, pancreatic necrosis, and intensive care unit (ICU) admission]. The revised Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool was used to evaluate the quality of diagnostic accuracy studies. The threshold effect was evaluated for each outcome. The sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and the area under the summary receiver operating characteristic (SROC) curve (AUC) as well as 95% confidence intervals (CI) were calculated. The DeLong test was used for AUC comparisons. For the outcome evaluated by over 9 studies, publication bias was assessed using the Deeks' funnel plot asymmetry test. RESULTS: Totally 17 studies of 5476 AP patients were included. For severity, the pooled sensitivity of the Ranson and BISAP was 0.95 (95%CI: 0.87, 0.98) and 0.67 (95%CI: 0.27, 0.92); the pooled specificity of the Ranson and BISAP was 0.74 (0.52, 0.88) and 0.95 (95%CI: 0.85, 0.98); the pooled AUC of the Ranson and BISAP was 0.95 (95%CI: 0.93, 0.97) and 0.94 (95%CI: 0.92, 0.96) (P = 0.480). For mortality, the pooled sensitivity of the Ranson and BISAP was 0.89 (95%CI: 0.73, 0.96) and 0.77 (95%CI: 0.58, 0.89); the pooled specificity of the Ranson and BISAP was 0.79 (95%CI: 0.68, 0.87) and 0.90 (95%CI: 0.86, 0.93); the pooled AUC of the Ranson and BISAP was 0.91 (95%CI: 0.88, 0.93) and 0.92 (95%CI: 0.90, 0.94) (P = 0.480). For organ failure, the pooled sensitivity of the Ranson and BISAP was 0.84 (95%CI: 0.76, 0.90) and 0.78 (95%CI: 0.60, 0.90); the pooled specificity of the Ranson and BISAP was 0.84 (95%CI: 0.63, 0.94) and 0.90 (95%CI: 0.72, 0.97); the pooled AUC of the Ranson and BISAP was 0.86 (95%CI: 0.82, 0.88) and 0.90 (95%CI: 0.87, 0.93) (P = 0.110). For pancreatic necrosis, the pooled sensitivity of the Ranson and BISAP was 0.63 (95%CI: 0.35, 0.84) and 0.63 (95%CI: 0.23, 0.90); the pooled specificity of the Ranson and BISAP was 0.90 (95%CI: 0.77, 0.96) and 0.93 (95%CI: 0.89, 0.96); the pooled AUC of the Ranson and BISAP was 0.87 (95%CI: 0.84, 0.90) and 0.93 (95%CI: 0.91, 0.95) (P = 0.001). For ICU admission, the pooled sensitivity of the Ranson and BISAP was 0.86 (95%CI: 0.77, 0.92) and 0.63 (95%CI: 0.52, 0.73); the pooled specificity of the Ranson and BISAP was 0.58 (95%CI: 0.55, 0.61) and 0.84 (95%CI: 0.81, 0.86); the pooled AUC of the Ranson and BISAP was 0.92 (95%CI: 0.81, 1.00) and 0.86 (95%CI: 0.67, 1.00) (P = 0.592). CONCLUSION: The Ranson score was an applicable tool for predicting severity and prognosis of AP patients with reliable diagnostic accuracy in resource and time-limited settings. Future large-scale studies are needed to verify the findings.

2-Azidobenzaldehyde-Based [4+2] Annulation for the Synthesis of Quinoline Derivatives.

Quinoline is a privileged heterocyclic ring which can be found in many drug molecules and bioactive compounds. The development of synthetic methods for making quinoline derivatives continuously attracts the interest of organic and medicinal chemists. This paper highlights 2-azidobenzaldehyde-based [4+2] annulation for the synthesis of quinoline derivatives including fused and spiro-quinolines, quinoline-4-ols, 4-aminoquinolines, and related compounds.

Synergistic amelioration between Ligusticum striatum DC and borneol against cerebral ischemia by promoting astrocytes-mediated neurogenesis.

ETHNOPHARMACOLOGICAL RELEVANCE: Ligusticum chuanxiong Hort (LCH), with the accepted name of Ligusticum striatum DC in "The Plant List" database, is a widely used ethnomedicine in treating ischemic stroke, and borneol (BO) is usually prescribed with LCH for better therapy. Our previous study confirmed their synergistic effect on neurogenesis against cerebral ischemia. However, the underlying mechanism is still unclear. AIM OF THE STUDY: More and more evidence indicated that astrocytes (ACs) might be involved in the modulation of neurogenesis via polarization reaction. The study was designed to explore the synergic mechanism between LCH and BO in promoting astrocyte-mediated neurogenesis. MATERIALS AND METHODS: After primary cultures and identifications of ACs and neural stem cells (NSCs), the oxygen-glucose deprivation (OGD) model and the concentrations of LCH and BO were optimized. After the OGD-injured ACs were treated by LCH, BO, and their combination, the conditioned mediums were used to culture the OGD-injured NSCs. The proliferation, migration, and differentiation of NSCs were assessed, and the secretions of BDNF, CNTF, and VEGF from ACs were measured. Then the expressions of C3 and PTX3 were detected. Moreover, the mice were performed a global cerebral ischemia/reperfusion model and treated with LCH and (or) BO. After the assessments of Nissl staining, the expressions of Nestin, DCX, GFAP, C3, PTX3, p65 and p-p65 were probed. RESULTS: The most appropriate duration of OGD for the injury of both NSCs and ACs was 6 h, and the optimized concentrations of LCH and BO were 1.30 µg/mL and 0.03 µg/mL, respectively. The moderate OGD environment induced NSCs proliferation, migration, astrogenesis, and neurogenesis, increased the secretions of CNTF and VEGF from ACs, and upregulated the expressions of C3 and PTX3. For the ACs, LCH further increased the secretions of BDNF and CNTF, enhanced PTX3 expression, and reduced C3 expression. Additionally, the conditioned medium from LCH-treated ACs further enhanced NSC proliferation, migration, and neurogenesis. The in vivo study showed that LCH markedly enhanced the Nissl score and neurogenesis, and decreased astrogenesis which was accompanied by downregulations of C3, p-p65, and p-p65/p65 and upregulation of PTX3. BO not only decreased the expression of C3 in ACs both in vitro and in vivo but also downregulated p-p65 and p-p65/p65 in vivo. Additionally, BO promoted the therapeutic effect of LCH for most indices. CONCLUSION: A certain degree of OGD might induce ACs to stimulate the proliferation, astrogenesis, and neurogenesis of NSCs. LCH and BO exhibited a marked synergy in promoting ACs-mediated neurogenesis and reducing astrogenesis, in which LCH played a dominant role and BO boosted the effect of LCH. The mechanism of LCH might be involved in switching the polarization of ACs from A1 to A2, while BO preferred to inhibit the formation of A1 phenotype via downregulating NF-κB pathway.

Exploring the effect of different typical plant community on human stress reduction: a field experiment.

Research has demonstrated the positive effect of natural environment on human restoration and well-being. Time spent in nature can often alleviate both physiological and psychological stress. However, few studies have discussed the environmental health effects of the nature's components and characteristics. Sixty volunteers were recruited and one manufactured environment and five different natural environments were randomly assigned to them, including coniferous forests (pure coniferous forest-PC and mixed coniferous forest-MC), broad-leaved forests (pure broad-leaved forest-PB and mixed broad-leaved forest-MB), and mixed forest (mixed coniferous and broad-leaved forest-MCB). Each volunteer sat in a built or natural environment and looked around the environment for 15 min. Physiological (HR, HRV, BP, pulse rate and salivary cortisol) and psychological indicators (POMS and STAI) were used to evaluate the changes in their stress level. Results indicated a strong difference in HR, HRV, POMS and STAI between the built and natural environment, which showed that natural environment can lower the stress level. MC had the best effect on relieving physiological stress, whereas MCB is most successful in improving emotional state and reducing anxiety. Broad-leaved forest and mixed forest significantly affected the DBP and vigor level of the subjects, respectively. While coniferous forest did significantly increase the concentration of salivary cortisol in subjects. The study confirmed that compared to the built environment, the natural environment can relieve the human body's physical and psychological stress and negative emotions, while significantly increasing vitality. And different plant communities also have different effects on the physiological and psychological indicators of the subjects. These results will provide scientific basis for the construction and improvement of urban green space environment.