Enhancing the Stability of Metallic Li Anodes for Aprotic Li-O2 Batteries with Dual-Anion Electrolytes.

Despite the impressive specific capacity of Li-O2 batteries, challenges persist, particularly with lithium metal anode (LMA). These include dendritic growth and unstable solid electrolyte interface (SEI) layers, which become more pronounced in an oxygen-rich environment, a typical operation scenario for Li-O2 batteries. Herein, utilizing a hybrid dual anion electrolyte (DAE) strategy, which incorporates both inorganic LiNO3 and organic Li[(FSO2)(C2F5SO2)N] (LiFPFSI) salts, the dendritic growth is evidently inhibited by creating a "concrete-like" SEI structure. Simultaneously, it fosters the development of a fluorine-rich SEI layer. Consequently, a robust, compact, and stable barrier is formed, adeptly suppressing side reactions between LMA and the electrolyte, particularly those relevant to dissolved O2. The practicality and efficiency of this DAE strategy are validated across a variety of battery types including Li/Li, Li/Cu, and notably Li-O2 batteries, which showcased significantly improved reversibility and durability. These results underscore the important role of multifunctional salts in interphase engineering for LMA, which could lead to advancements in Li-O2 batteries.

Analysis of factors associated with positive surgical margins and the five-year survival rate after prostate cancer resection and predictive modeling.

Background: This study analyzed the risk factors associated with positive surgical margins (PSM) and five-year survival after prostate cancer resection to construct a positive margin prediction model. Methods: We retrospectively analyzed the clinical data of 148 patients treated with prostatectomy. The patients were divided into PSM group and Negative surgical margins (NSM) group. Several parameters were compared between the groups. All patients were followed up for 60 months. The risk factors for PSM and five-year survival were evaluated by univariate analysis, followed by multifactorial dichotomous logistic regression analysis. Finally, ROC curves were plotted for the risk factors to establish a predictive model for PSM after prostate cancer resection. Results: (1) Serum PSA, percentage of positive puncture stitches, clinical stage, surgical approach, Gleason score on puncture biopsy, and perineural invasion were significantly associated with the risk of PSM (P < 0.05). Serum PSA, perineural invasion, Gleason score on puncture biopsy, and percentage of positive puncture stitches were independent risk factors for PSM. (2) Total prostate-specific antigen (tPSA) by puncture, nutritional status, lymph node metastasis, bone metastasis, and seminal vesicle invasion may be risk factors for five-year survival. Lymph node metastasis and nutritional status were the main risk factors for the five-year survival of patients with prostate cancer. (3) After plotting the ROC curve, the area under the curve (AUC) [AUC: 0.776, 95%, confidence interval (CI): 0.725 to 0.854] was found to be a valid predictor of PSM; the AUC [AUC: 0.664, 95%, confidence interval (CI): 0.576 to 0.753] was also a valid predictor of five-year survival (P < 0.05). (4) The scoring system had a standard error of 0.02 and a cut-off value of 6. It predicted PSM after prostate cancer resection with moderate efficacy. Conclusions: Serum PSA, perineural invasion, puncture biopsy Gleason score, and percentage of positive puncture stitches were independent risk factors for positive surgical margins (PSM). Also, lymph node metastasis and nutritional status were the main risk factors for the five-year survival of patients with prostate cancer. Overall, the prediction efficacy of this scoring system concerning the risk of PSM after prostate cancer resection was moderate.

Impulse oscillometry in the diagnosis of cough variant asthma in children.

BACKGROUND: Cough variant asthma (CVA) is one of the most common causes of chronic cough in children worldwide. The diagnosis of CVA in children remains challenging. This study aimed to assess the diagnostic utility of impulse oscillometry (IOS) pulmonary function in children with CVA. METHODS: This study included children aged 4 to 12 years diagnosed with CVA who underwent IOS pulmonary function and bronchodilation (BD) tests. A control group of healthy children was matched. Pre- and post-BD IOS parameters were recorded and presented as mean ± standard deviation or median. Receiver operating characteristic (ROC) curves were plotted, and the area under the curve (AUC) was calculated to evaluate the discriminatory potential of the IOS parameters for diagnosing CVA. RESULTS: A total of 180 patients with CVA and 65 control subjects were included. The baseline IOS parameters in the CVA group, except X5%pred, were significantly greater compared to the control group. After inhalation of salbutamol sulfate, all IOS parameters improved significantly in the CVA group. However, Z5%pred, R5%pred, and R20%pred remained greater in the CVA group compared to the control group. The improvement rates of IOS parameters in the CVA group significantly surpassed those in the control group. The ROC curve results for pre-BD IOS parameters and the improvement rate during the BD test showed that the combinations of pre-Z5%pred+△Z5% and pre-R5%pred+△R5% achieved the highest AUC value of 0.920 and 0.898, respectively. The AUC values of these combined parameters surpassed those of individual ones. CONCLUSIONS: This study highlights that children with CVA exhibit greater IOS parameters compared to healthy children. The changes in IOS parameters during the BD test provided valuable diagnostic information for CVA, and the combination of various parameters can help pediatricians accurately identify CVA in children.

Medication adherence and costs of medical care among patients with Parkinson's disease: an observational study using electronic medical records.

BACKGROUND: Adherence to antiparkinsonian drugs (APDs) is critical for patients with Parkinson's disease (PD), for which medication is the main therapeutic strategy. Previous studies have focused on specific disorders in a single system when assessing clinical factors affecting adherence to PD treatment, and no international comparative data are available on the medical costs for Chinese patients with PD. The present study aimed to evaluate medication adherence and its associated factors among Chinese patients with PD using a systematic approach and to explore the impact of adequate medication adherence on direct medical costs. METHODS: A retrospective analysis was conducted using the electronic medical records of patients with PD from a medical center in China. Patients with a minimum of two APD prescriptions from January 1, 2016 to August 15, 2018 were included. Medication possession ratio (MPR) and proportion of days covered were used to measure APD adherence. Multiple linear regression analysis was used to identify factors affecting APD adherence. Gamma regression analysis was used to explore the impact of APD adherence on direct medical costs. RESULTS: In total, 1,712 patients were included in the study, and the mean MPR was 0.68 (± 0.25). Increased number of APDs and all medications, and higher daily levodopa-equivalent doses resulted in higher MPR (mean difference [MD] = 0.04 [0.03-0.05]; MD = 0.02 [0.01-0.03]; MD = 0.03 [0.01-0.04], respectively); combined digestive system diseases, epilepsy, or older age resulted in lower MPR (MD = -0.06 [-0.09 to -0.03]; MD = -0.07 [-0.14 to -0.01]; MD = -0.02 [-0.03 to -0.01], respectively). Higher APD adherence resulted in higher direct medical costs, including APD and other outpatient costs. For a 0.3 increase in MPR, the two costs increased by $34.42 ($25.43-$43.41) and $14.63 ($4.86-$24.39) per year, respectively. CONCLUSIONS: APD adherence rate among Chinese patients with PD was moderate and related primarily to age, comorbidities, and healthcare costs. The factors should be considered when prescribing APDs.

Efficacy of Breast-Conserving Surgery Versus Modified Radical Surgery in the Treatment of Early Breast Cancer: A Meta-Analysis.

Objective: The study aims to assess and compare the outcomes of modified radical surgery, preserving the nipple-areola complex, against radical mastectomy in patients with triple-negative breast cancer. Emphasis is placed on the clinical significance of this comparison, including its potential impact on patient outcomes, quality of life, and healthcare resources. Methods: Relevant literature from January 2017 to January 2022 was searched in the following databases: PubMed, Embase, MEDLINE, Science Citation Index, Web of Science, China National Knowledge Internet, CCD, and CSPD with keywords. The electric search yielded 613 relevant articles, including 351 from Pubmed, 187 from Embase, 5 from MEDLINE, 21 from CNKI, 4 from CCD, and 45 from CSPD. After duplicate screening, 185 items were eliminated, leaving 428 articles. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated with RevMan 5.3, and sensitivity analysis, cumulative meta-analysis, and publication bias analysis were also performed. A total of 613 relevant articles were collected from the above databases, among which 428 articles remained after the initial screening and were further screened based on the established inclusion and exclusion criteria. The efficacy of modified radical surgery and breast-conserving surgery in the treatment of early breast cancer was assessed by analyzing outcome indicators, including recurrence rate, distant metastatic rate, and three-year survival rate. The methods section details a systematic approach to data collection and analysis, specifying the databases and time frame for the literature search and the statistical tools used for the meta-analysis. The selection process, from the initial number of articles to the final inclusion based on defined criteria, is transparent, ensuring the study's methodological robustness in evaluating the efficacy of surgeries for early breast cancer. Results: Finally, ten articles were found to match the criteria and included in this study. According to the meta-analysis, there was no statistically significant difference between the breast-conserving therapy (BCT) and modified radical mastectomy (MRM) groups in terms of the recurrence rate (OR = 0.76, 95%CI = 0.39, 1.55, P > .05) and distant metastatic rate (OR = 0.81, 95%CI = 0.46, 1.31, P > .05). Nevertheless, the three-year survival rate was 85.2% in the BCT group and 91.7% in the MRM group; a statistically significant difference was observed in the three-year survival rate (OR = 1.47, 95%CI = 1.01, 2.37, P = .03) between the BCT and MRM groups. Accordingly, breast-conserving surgery and modified radical surgery produced comparable clinical outcomes for the treatment of early breast cancer. Conclusion: In the treatment of early breast cancer, breast-conserving surgery has the advantages of less bleeding, fewer clinical complications, and favorable cosmetic outcomes compared with modified radical surgery. Furthermore, patients with breast-conserving surgery showed comparable recurrence and distant metastatic rates to those with modified radical surgery in postoperative follow-up, which, therefore is a suitable treatment option for the widespread recommendation. The study's findings hold significant clinical relevance, implying that while BCT remains a viable option, MRM may offer a survival advantage. This insight empowers both patients and clinicians in making informed, personalized treatment decisions tailored to individual circumstances.

Sinomenine protects against atherosclerosis in apolipoprotein E-knockout mice by inhibiting of inflammatory pathway.

Atherosclerosis, a multifaceted and persistent inflammatory condition, significantly contributes to the progression of cardiocerebrovascular disorders, such as myocardial infarctions and cerebrovascular accidents. It involves the accumulation of cholesterol, fatty deposits, calcium and cellular debris in the walls of arteries, leading to the formation of plaques. Our aim is to investigate the potential of sinomenine to counteract atherosclerosis in mice lacking Apolipoprotein E (ApoE-/-) Mice. We employed the high-fat diet-induced method to induce atherosclerosis in ApoE-/- mice, and the mice were treated with sinomenine (5, 10, and 15 mg/kg) and simvastatin (0.5 mg/kg) for 12 weeks. Body weight, water intake, and food intake were assessed. Lipid parameters, oxidative stress, inflammatory cytokines, and mRNA levels were estimated. Sinomenine treatment remarkably (P < 0.001) suppressed body weight, along with food and water intake. Sinomenine altered the levels of total cholesterol (TC), high-density lipoprotein (HDL), triglyceride (TG), low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL), which were modulated in the atherosclerosis group. Sinomenine treatment also altered the levels of oxidative stress parameters such as glutathione peroxidase (GPx), catalase (CAT), malonaldehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH). In addition, it modulated cardiac parameters like C-reactive protein (CRP), endothelin-1 (ET-1), thromboxane B2 (TXB2), nitric oxide (NO), cardiac troponin I (cTnI), lactate dehydrogenase (LDH), and creatinine kinase isoenzymes (CK-MB). Inflammatory cytokines interleukin (IL)-1α, IL-1ß, TNF-α, IL-6, and IL-10 were also affected. Sinomenine further suppressed the mRNA expression of IL-6, IL-17, IL-10, tumor necrosis factor-α (TNF-α), Il-1ß, monocyte chemoattractant protein-1 (MCP-1), MCP-2, MCP-3, transforming Growth Factor-1ß (TGF-1ß), vascular cell adhesion molecule 1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1). The results suggest that sinomenine remarkably suppressed the development of atherosclerosis in the early stage.

SFRP5 Partially Inhibits the Proliferation and Migration of Airway Smooth Muscle Cells in Children with Asthma by Regulating the Wnt/ß-Catenin Signaling Pathway.

BACKGROUND: Childhood asthma is a chronic inflammatory disease of the respiratory tract characterized by bronchial inflammation, airway hyperresponsiveness, airflow disorder, and obstruction. Secreted frizzled-related protein 5 (SFRP5) may be associated with respiratory inflammatory diseases. This study investigated the effect of SFRP5 on human airway smooth muscle cells (HASMCs) to provide new ideas for treating asthma. METHODS: A total of 30 children with asthma and 30 children who had a physical examination at the same time were selected and divided into asthma and healthy groups. Serum SFRP5 levels were determined by enzyme-linked immunosorbent assay (ELISA) and real-time quantitative polymerase chain reaction (RT-qPCR). Lipofectamine 2000™ regent was used to transfect the SFRP5 overexpression plasmid (pc-SFRP5) or corresponding negative control (pc-NC) into HASMCs. HASMCs were treated with 10 µg/L platelet-derived growth factor-BB (PDGF-BB), which is an inducer to mimic the asthma-like condition at the cellular level of childhood asthma. HASMCs were divided into control, PDGF-BB (PDGF-BB treatment), PDGF-BB+pc-NC (pc-NC transfection and PDGF-BB treatment), and PDGF-BB+pc-SFRP5 (pc-SFRP5 transfection and PDGF-BB treatment) groups. Cell proliferation was measured by 5-ethynyl-2'-deoxyuridine (EdU) and cell counting kit-8 (CCK-8) assay. Cell migration was detected by Transwell assay. The protein expression was detected by western blot. RESULTS: Serum SFRP5 expression in the asthmatic group was decreased versus the healthy group (p < 0.0001). Induction of PDGF-BB decreased SFRP5 expression in HASMCs (p < 0.01). SFRP5 expression in the pc-SFRP5 group was increased (p < 0.01). The proliferation and migration of HASMCs increased after PDGF-BB treatment (p < 0.001, p < 0.0001), indicating that the asthma model was successfully inducted in vitro. Moreover, the expression of ß-catenin, cellular-myelocytomatosis viral oncogene (c-Myc), and cyclinD1 proteins in HASMCs increased after PDGF-BB treatment (p < 0.0001). SFRP5 overexpression partly inhibited PDGF-BB-induced proliferation, migration, and expressions of ß-catenin, c-Myc, and cyclinD proteins in HASMCs (p < 0.01, p < 0.001, p < 0.0001). CONCLUSIONS: Serum SFRP5 expression decreases in children with asthma. SFRP5 overexpression partially inhibits PDGF-BB-induced HASMC proliferation and migration by regulating the wingless-type mouse mammary tumor virus (MMTV) integration site family (Wnt)/ß-catenin pathway.

Establishment of a diagnostic model based on immune-related genes in children with asthma.

Objective: Allergic asthma is driven by an antigen-specific immune response. This study aimed to identify immune-related differentially expressed genes in childhood asthma and establish a classification diagnostic model based on these genes. Methods: GSE65204 and GSE19187 were downloaded and served as training set and validation set. The immune cell composition was evaluated with ssGSEA algorithm based on the immune-related gene set. Modules that significantly related to the asthma were selected by WGCNA algorithm. The immune-related differentially expressed genes (DE-IRGs) were screened, the protein-protein interaction network and diagnostic model of DE-IRGs was constructed. The pathway and immune correlation analysis of hub DE-IRGs was analyzed. Results: Eight immune cell types exhibited varying levels of abundance between the asthma and control groups. A total of 112 differentially expressed immune-related genes (DE-IRGs) was identified. Through the application of four ranking methods (MCC, MNC, DEGREE, and EPC), 17 hub DE-IRGs with overlapping significance were further selected. Subsequently, 8 optimized were identified using univariate logistic regression analysis and the LASSO regression algorithm, based on which a robust diagnostic model was constructed. Notably, TNF and CD40LG emerged as direct participants in asthma-related signaling pathways, displaying a positive correlation with the immune cell types of immature B cells, activated B cells, activated CD8 T cells, activated CD4 T cells, and myeloid-derived suppressor cells. Conclusion: The diagnostic model constructed using the DE-IRGs (CCL5, CCR5, CD40LG, CD8A, IL2RB, PDCD1, TNF, and ZAP70) exhibited high and specific diagnostic value for childhood asthma. The diagnostic model may contribute to the diagnosis of childhood asthma.

Spirometry in the diagnosis of cough variant asthma in children.

OBJECTIVE: This study aimed to assess the diagnostic utility of spirometry, particularly focusing on small airway parameters, in children with cough variant asthma (CVA). METHODS: This study included children aged 5-12 years with a diagnosis of CVA. Pre- and postbronchodilation spirometry parameters, including FEV1 %pred, FVC%pred, FEV1 /FVC%pred, PEF%pred, FEF25 %pred, FEF50 %pred, FEF75 %pred, MMEF%pred, were recorded. Receiver operating characteristic curves were plotted, and the area under the curve (AUC) was calculated to assess the discriminatory potential of these spirometry parameters for CVA. A prediction model based on logistic regression (LR) was performed. RESULTS: A total of 200 patients with CVA and 73 control subjects were included. Baseline spirometry parameters in the CVA group, except for FVC%pred, were significantly lower compared to the control group. After inhalation of salbutamol sulfate, all parameters showed significant improvement in the CVA group. However, these parameters, except for FEV1 %pred and FVC%pred, remained lower in the CVA group compared to the control group. The improvement rate of each parameter in the CVA group, except for ∆ FVC%, was significantly higher than that in the control group. △ MMEF% achieved the highest AUC of 0.797 with a threshold value of 16.09%, followed by △ FEF75 % (0.792), △ FEV1 % (0.756), and △ FEF50 % (0.747) with threshold values of 19.01%, 4.48%, and 19.4%, respectively. The clinical prediction model included four variables (age, △ FEF25 %, △ FEF75 %, and △ MMEF%) and demonstrated excellent performance distinguishing patients with and without CVA (AUC = 0.850). In the CVA group, the △ FEV1 % showed a positive correlation with small airway parameters. CONCLUSIONS: This study highlights that children with CVA exhibit lower pulmonary function parameters compared to healthy children. Changes in small airway parameters during bronchodilator tests can be valuable in diagnosing CVA, and the LR prediction model incorporating age and several pulmonary parameters can assist physicians in accurately identifying CVA in clinical practice.

Covalent Organic Framework Fiber-Constructed Artificial Solid Electrolyte Interphase Layer: Facilitated Uniform Deposition of Li+ and Encapsulated Li Dendrite.

Due to ultrahigh theoretical capacity and ultralow redox poteneial, lithium metal is considered as a promising anode material. However, uneven lithium deposition, uncontrollable lithium dendrite formation, and fragile solid electrolyte interphase (SEI) lead to low lithium utilization, rapid capacity decay, and poor cycle performance. Herein, a robust artificial SEI film by coating the lithium surface with fibrous covalent organic framework (Fib-COF) was constructed, which effectively prevented dendrite penetration and battery short-circuits. Experimental results demonstrated that the Fib-COF-decorated batteries showcased higher Coulombic efficiency (CE), extended cycling stability, and superior electrolyte compatibility. The strong affinity of the carbonyl group in Fib-COF towards Li+ contributes to facilitating the Li+ uniform transfer and nucleation. In situ optical microscopy dynamically revealed the formation process of dendrite-free interphase under the function of Fib-COF layer. As a result, the modified Li anode demonstrated remarkable cycle stability for more than 650 h at 20 mA cm-2 and 5 mAh cm-2 in ether-based electrolyte and 1000 h at 0.5 mA cm-2 and 0.5 mAh cm-2 in carbonate-based electrolyte. The dendrite-free Fib-COF@Li electrodes endowed higher specific capacities of 650 mAh g-1 for Fib-COF@Li|S full cell after 250 cycles and 120 mAh g-1 for Fib-COF @Li|LiFePO4 full cells after 300 cycles.

Pharmaceutical Therapies for Necroptosis in Myocardial Ischemia-Reperfusion Injury.

Cardiovascular disease morbidity/mortality are increasing due to an aging population and the rising prevalence of diabetes and obesity. Therefore, innovative cardioprotective measures are required to reduce cardiovascular disease morbidity/mortality. The role of necroptosis in myocardial ischemia-reperfusion injury (MI-RI) is beyond doubt, but the molecular mechanisms of necroptosis remain incompletely elucidated. Growing evidence suggests that MI-RI frequently results from the superposition of multiple pathways, with autophagy, ferroptosis, and CypD-mediated mitochondrial damage, and necroptosis all contributing to MI-RI. Receptor-interacting protein kinases (RIPK1 and RIPK3) as well as mixed lineage kinase domain-like pseudokinase (MLKL) activation is accompanied by the activation of other signaling pathways, such as Ca2+/calmodulin-dependent protein kinase II (CaMKII), NF-κB, and JNK-Bnip3. These pathways participate in the pathological process of MI-RI. Recent studies have shown that inhibitors of necroptosis can reduce myocardial inflammation, infarct size, and restore cardiac function. In this review, we will summarize the molecular mechanisms of necroptosis, the links between necroptosis and other pathways, and current breakthroughs in pharmaceutical therapies for necroptosis.

Improving the linearity of synaptic plasticity of single-walled carbon nanotube field-effect transistors via CdSe quantum dots decoration.

The linearity of synaptic plasticity of single-walled carbon nanotube field-effect transistor (SWCNT FET) was improved by CdSe quantum dots decoration. The linearity of synaptic plasticity in SWCNT FET with decorating QDs was further improved by reducing the P-type doping level from the atmosphere. The synaptic behavior of SWCNT FET is found to be dominated by the charging and discharging processes of interface traps and surface traps, which are predominantly composed of H2O/O2redox couples. The improved synaptic behavior is mainly due to the reduction of the interface trap charging process after QDs decoration. The inherent correlation between the device synaptic behavior and the electron capture process of the traps are investigated through charging-based trap characterization. This study provides an effective scheme for improving linearity and designing new-type SWCNT synaptic devices.

A highly tunable photoelectric response of graphene field-effect transistor with lateral P-N junction in channel.

This paper reports a highly tunable photoelectric response of graphene field-effect transistor (GFET) with lateral P-N junction in channel. The poly(sulfobetaine methacrylate) (PSBMA) provides strong N-type doping on graphene due to the dipole moment of pendent groups after ultraviolet annealing in high vacuum. A lateral P-N junction is introduced into the channel of the GFET by partially covering the graphene channel with PSBMA. With such P-N junction in the channel, the GFET exhibits a highly tunable photoelectric response over a wide range of exciting photon wavelength. With a lateral P-N junction in the channel, the polarity of photocurrent (Iph) of the GFET switches three times as the back-gate voltage (VBG) scan over two Dirac-point voltages. The underlying physical mechanism of photoelectric response is attributed to photovoltaic and photo-induced bolometric effect, which compete to dominatingIphat variousVBG. This provides a possible strategy for designing new phototransistors or optoelectronic device in the future.

Critical Factors Affecting the Catalytic Activity of Redox Mediators on Li-O2 Battery Discharge.

Redox mediators (RMs) have a substantial ability to govern oxygen reduction reaction (ORR) in Li-O2 batteries, which can realize large capacity and high-rate capability. However, studies on understanding RM-assisted ORR mechanisms are still in their infancy. Herein, a quinone-based molecule, vitamin K1 (VK1), is first used as the ORR RM for Li-O2 batteries, together with 2,5-di-tert-butyl-1,4-benzoquinone (DBBQ), to elucidate key factors on the catalytic activity of RMs. By combining experiments and first-principle computations, we demonstrate that the reduced VK1 has strong oxygen affinity and can effectively retard the deposition of Li2O2 films on the electrode surface, thereby guaranteeing enough active sites for electron transfer. Besides, the low reaction free energy of disproportionation of the Li(VK1)O2 intermediate into Li2O2 also significantly accelerates the ORR process. Consequently, the catalytic activity of VK1 is significantly boosted, and the discharge capacity of VK1-assisted batteries is 3.2-4.5 times that of DBBQ-assisted batteries. This study provides new insight for better understanding the working roles of RMs in Li-O2 batteries.

NF-κB and EGFR participate in S1PR3-mediated human renal cell carcinomas progression.

The bioactive lipid sphingosine 1-phosphate (S1P) is implicated in many pivotal processes for the physiological and pathological actions via activating five types of G-protein-coupled S1P receptors (S1PR1-5). The role of S1P in renal cell carcinoma (RCC) and its receptor subtype specific mediating mechanism are poorly studied. So we focus on the regulatory role of S1P in RCC progression and the receptor subtypes involved in S1P-induced actions, intending to further clarify a novel therapeutic target for RCC. Analysis of The Cancer Genome Atlas (TCGA) databases showed that the patients with high expression of S1PR3 had significantly worse overall than with low expression. We further demonstrated that S1P could promote proliferation, migration, and epithelial-mesenchymal transition (EMT) of renal cancer cells in vitro, and the actions were enhanced with the increase of S1PR3 expression. Meanwhile, the results in animal experiments also showed that S1PR3 could accelerate tumorigenesis and metastasis of RCC. Our study also clarified the mechanism for S1P induced cell proliferation is mediated by S1PR3/Gi/p38/Akt/p65/cyclin D1-CDK4 pathway and the main pathway for migration is S1PR3/Gi/q/ERK/p38/p65. In addition, S1PR3 was involved in epidermal growth factor (EGF)-induced actions by enhancing protein expression, not by transactivation of epidermal growth factor receptor (EGFR). These results also further supported our conclusion that the carcinogenic role of S1P/S1PR3 axis. Thus, our findings provide that S1PR3 may be a promising small molecular therapeutic target for S1PR3 expressed cancers.

Heparin interacts with the main protease of SARS-CoV-2 and inhibits its activity.

The ability of SARS-CoV-2 to replicate in host cells is dependent on its main protease (Mpro, also called 3CLpro) that cut the viral precursor polyproteins and is a major target for antiviral drug design. Here, we showed that heparin interacts with the Mpro of SARS-CoV-2 and inhibits its activity. Protein fluorescence quenching showed that heparin strongly binds to the Mpro protein with dissociation constants KD of 16.66 and 31.60 µM at 25 and 35 °C, respectively. From thermodynamic parameters of the interaction, there are hydrophobic and hydrogen bond interactions between them. Fluorescence resonance energy transfer (FRET) assay demonstrated that heparin inhibits the proteolytic activity of Mpro with an inhibition constant Ki of 6.9 nM and a half maximal inhibitory concentrations (IC50) of 7.8 ± 2.6 nM. Furthermore, molecular docking analysis revealed that the recognition and binding groups of heparin within the active site of SARS-CoV-2 Mpro provide important new information for the characteristics of the interactions of heparin with the protease. Our finding suggested that heparin might have a potential role in inhibiting SARS-CoV-2 infection through inhibiting Mpro activity of SARS-CoV-2.

LDL-C and Total Stent Length are Independent Predictors of Periprocedural Myocardial Injury and Infarction for Unstable Angina Patients Undergoing Elective Percutaneous Coronary Intervention.

BACKGROUND: To investigate the predictive value of low-density lipoprotein cholesterol (LDL-C), total stent length and number of implanted stents in patients with unstable angina (UA) regarding myocardial injury and infarction during perioperative period. METHODS: Three hundred and fifteen consecutive UA patients between January 2015 and June 2018 were retrospectively recruited from two cardiac centers of Hebei Province, China. These patients had normal preprocedural cardiac troponin I (cTnI) and underwent uneventful revascularizations. The predictive value of baseline LDL-C level and total stent length was investigated by linking to post procedural cTnI value in this cohort. Meanwhile, other related clinical and procedural variables were analyzed. RESULTS: Baseline LDL-C level or LDL-C grade was correlated with post percutaneous coronary intervention (PCI) cTnI levels (r = 0.120, P = 0.01; r = 0.157, P = 0.004). LDL-C grade was an independent risk factor of perioperative myocardial injury and infarction (P < 0.05) after multivariable adjustment. The risk increased with the elevation of baseline LDL-C level. Compared to the lowest level group (<70 mg/dl), the group with 70-99 mg/dl carried three times higher risk (OR = 3.318; 95% CI: 1.167-9.436; P < 0.05). And, patients with LDL-C level ≥100 mg/dl had the worst prognosis (OR = 4.783; 95% CI: 1.736-13.180; P = 0.002). Besides, the study also found that the total length of stent was predictive of perioperative myocardial injury and infarction independently (OR = 1.037; 95% CI: 1.017-1.058; P = 0.001). CONCLUSION: Baseline LDL-C level and total stent length were independent predictors of periprocedural myocardial injury and infarction in UA patients undergoing elective PCI.

Prognostic value of the systemic immune-inflammation index in patients with breast cancer: a meta-analysis.

BACKGROUND: Although previous studies have evaluated the prognostic role of the systemic immune-inflammation index (SII) in patients with breast cancer, the results were inconsistent. Therefore, in this context, we aimed to identify the prognostic and clinicopathological value of the SII in patients with breast cancer by performing a meta-analysis. METHODS: A literature search was using PubMed, Web of Science, EMBASE, and Cochrane Library databases for relevant articles, from their inception to May 12, 2020. The prognostic value of the SII in breast cancer was assessed by pooling the hazard ratios (HRs) with 95% confidence intervals (CIs). The clinical outcomes included the overall survival (OS), disease-free survival (DFS), recurrence-free survival (RFS), and distant metastasis-free survival (DMFS). The methodological quality of all the included studies was evaluated using the Newcastle-Ottawa quality assessment scale. The odds ratios (ORs) with 95% CIs were combined to evaluate the correlation between the SII and clinicopathological characteristics of patients with breast cancer. Publication bias was evaluated using the Begg funnel plot and the Egger linear regression test. All statistical analyses were performed using Stata software, version 12.0 (Stata Corporation, College Station, TX, USA). A p value of < 0.05 was considered statistically significant. RESULTS: Eight studies involving 2642 patients were included in the current meta-analysis. The combined data showed that patients with a high SII had worse OS (HR = 1.79, 95% CI 1.33-2.42, p < 0.001), poorer DFS/RFS (HR = 1.79, 95% CI 1.31-2.46, p < 0.001), and inferior DMFS (HR = 1.64, 95% CI 1.32-2.03, p < 0.001) than patients with a low SII. In addition, a high SII was correlated with the presence of lymph node metastasis (OR = 1.38, 95% CI 1.12-1.69, p = 0.002), higher T stage (OR = 1.49, 95% CI 1.17-1.89, p < 0.001), advanced TNM stage (OR = 1.37, 95% CI 1.07-1.77, p = 0.014), and higher histological grade (OR = 3.71, 95% CI 1.00-13.73, p = 0.049). However, there was no significant association between the SII and the pathological type (OR = 0.82, 95% CI 0.55-1.23, p = 0.345) or lymphatic invasion (OR = 1.30, 95% CI 0.82-2.08, p = 0.266). CONCLUSIONS: The results of our meta-analysis suggest that an elevated SII predicts poor survival outcomes and is associated with clinicopathological features that indicate tumor progression of breast cancer.