Design, synthesis, and biological evaluation of novel benzimidazole derivatives as anti-cervical cancer agents through PI3K/Akt/mTOR pathway and tubulin inhibition.

Phosphatidylinositol 3-kinase (PI3K) is one of the most attractive therapeutic targets for cervical cancer treatment. In this study, we designed and synthesized a series of benzimidazole derivatives and evaluated their anti-cervical cancer activity. Compound 4r exhibited strong antiproliferative activity in different cervical cancer cell lines HeLa, SiHa and Ca Ski, and relative lower cytotoxicity to normal hepatic and renal cell lines LO2 and HEK-293t (IC50 values were at 21.08 µM and 23.96 µM respectively). Its IC50 value was at 3.38 µM to the SiHa cells. Further mechanistic studies revealed that 4r induced apoptosis, arrested cell cycle in G2/M phase, suppressed PI3K/Akt/mTOR pathway and inhibit the polymerization of tubulin. Molecular docking study suggested that 4r formed key H-bonds action with PI3Kα (PDB ID:8EXU) and tubulin (PDB ID:1SA0). Zebrafish acute toxicity experiments showed that high concentrations of 4r did not cause death or malformation of zebrafish embryos. All these results demonstrated that 4r would be a promising lead candidate for further development of novel PI3K and tubulin dual inhibitors in cervical cancer treatment.

Characterization and childhood exposure assessment of toxic heavy metals in household dust under true living conditions from 10 China cities.

Health hazards caused by metal exposure in household dust are concerning environmental health problems. Exposure to toxic metals in household dust imposes unclear but solid health risks, especially for children. In this multicenter cross-sectional study, a total of 250 household dust samples were collected from ten stratified cities in China (Panjin, Shijiazhuang, Qingdao, Lanzhou, Luoyang, Ningbo, Xi'an, Wuxi, Mianyang, Shenzhen) between April 2018 and March 2019. Questionnaire was conducted to gather information on individuals' living environment and health status in real-life situations. Multivariate logistic regression and principal component analysis were conducted to identify risk factors and determine the sources of metals in household dust. The median concentration of five metals in household dust from 10 cities ranged from 0.03 to 73.18 µg/g. Among the five heavy metals, only chromium in household dust of Mianyang was observed significantly both higher in the cold season and from the downwind households. Mercury, cadmium, and chromium were higher in the third-tier cities, with levels of 0.08, 0.30 and 97.28 µg/g, respectively. There were two sources with a contribution rate of 38.3 % and 25.8 %, respectively. Potential risk factors for increased metal concentration include long residence time, close to the motorway, decoration within five years, and purchase of new furniture within one year. Under both moderate and high exposure scenarios, chromium showed the highest level of exposure with 6.77 × 10-4 and 2.28 × 10-3 mg·kg-1·d-1, and arsenic imposed the highest lifetime carcinogenic risk at 1.67 × 10-4 and 3.17 × 10-4, respectively. The finding highlighted the priority to minimize childhood exposure of arsenic from household dust.

Corrigendum: Genetic liability for diet-derived circulating antioxidants, oxidative stress, and risk of osteoarthritis: a Mendelian randomization study.

[This corrects the article DOI: 10.3389/fnut.2023.1233086.].

Superior Laryngeal Nerve Block for Microlaryngoscopic Surgery: A Systematic Review and Meta-Analysis.

OBJECTIVES: To assess the safety and efficacy of superior laryngeal nerve block (SLNB) for microlaryngoscopic surgery (MLS). DATA SOURCES: PubMed, Embase, Web of Science, Ovid Medline, Cochrane Library, CNKI database, VIP database, Wanfang database, and trial registry databases. METHODS: PICOS principles were performed: adults undergoing MLS receiving SLNB compared with no-SLNB in randomized controlled trials were included. Primary outcome included the incidence of severe postoperative sore throat (POST). Secondary outcomes included perioperative mean arterial pressure (MAP) and heart rate (HR), incidence of severe postoperative cough, and anesthesia recovery time. RESULTS: Eleven articles with 728 patients were included. Results indicated that SLNB provides lower incidence of severe POST in post-extubation 30 min (relative ratio [RR] = 0.13; 95% confidence intervals [CIs]: 0.05 ~ 0.34), 2 h (RR = 0.09; 95% CI: 0.02 ~ 0.36), 4-6 h (RR = 0.11; 95% CI: 0.03 ~ 0.41), and 24 h (RR = 0.15; 95% CI: 0.03 ~ 0.83); lower MAP (tracheal intubation: standardized mean difference [SMD] = -1.59; 95% CI: -1.69 to -0.42); suspension laryngoscope insertion: (SMD = -0.98; 95% CI: -1.49 to -0.46); tracheal extubation: (SMD = -0.78; 95% CI:-1.24 to -0.31); post-extubation 5 min: (SMD = -0.95; 95% CI: -1.41 to -0.49); lower HR (tracheal intubation: mean difference [MD] = -9.71; 95% CI: -17.16 to -2.27); suspension laryngoscope insertion: (MD = -8.64; 95% CI: -16.79 to -0.49); tracheal extubation: (MD = -10.13; 95% CI: -17.86 to -2.39); post-extubation 5 min: (MD = -13.44; 95% CI: -22.53 to -4.35); lower incidence of severe postoperative cough in post-extubation 30 min (RR = 0.18; 95% CI: 0.06 ~ 0.57) and 2 h (RR = 0.13; 95% CI: 0.02 ~ 0.69); and shorter anesthesia recovery time (MD = -5.34; 95% CI: -8.81 to -1.86) compared to controls. CONCLUSIONS: SLNB could provide lower incidence of severe POST, more stable perioperative MAP and HR, lower incidence of severe postoperative cough, and shorter anesthesia recovery time for MLS. LEVEL OF EVIDENCE: I Laryngoscope, 134:3437-3446, 2024.

Ultrasound-guided puncture drainage versus surgical incision drainage for deep neck space abscesses: a protocol for a systematic review with meta-analysis and trial sequential analysis.

INTRODUCTION: Deep neck space abscesses (DNAs) are serious surgical emergencies, associated with life-threatening complications. Surgical incision and drainage combined with antibiotics is the main treatment for DNAs, but drawbacks still exist. Ultrasound-guided puncture drainage is an alternative treatment for some DNAs with limited clinical evidence. Hence, the optimal drainage technique for the treatment of DNAs remains unclear. Therefore, we will perform a protocol for a systematic review and meta-analysis to identify the efficacy of ultrasound-guided puncture drainage for DNAs. METHODS AND ANALYSIS: PubMed, Ovid Medline, Cochrane Library, Embase, Web of Science, China National Knowledge Infrastructure, Wanfang database, VIP database and trial registry databases will be searched from inception to September 2023 to identify randomised controlled trials of patients diagnosed with DNAs accepting ultrasound-guided puncture drainage. The primary outcome will be the length of hospital stay. The secondary outcomes will be the cure rate, incidence of retreatment, complications and overall cost to the healthcare system. Fixed-effects or random-effects model will be used according to the statistical heterogeneity. Mean differences or standardised mean differences with 95% CIs for continuous data and risk ratio (RR) with 95% CIs for dichotomous data. The Cochrane risk-of-bias tool 2, Grading of Recommendations Assessment, Development and Evaluation (GRADE) and trial sequential analysis will be conducted to evaluate the evidence quality and control the random errors. Funnel plots and Egger's regression test will be performed to evaluate publication bias. ETHICS AND DISSEMINATION: Ethical approval was not required for this systematic review protocol. The results will be disseminated through peer-reviewed publications. PROSPERO REGISTRATION NUMBER: CRD42023441031.

Evaluating the Anti-Melanoma Effects and Toxicity of Cinnamaldehyde Analogues.

Cinnamaldehyde (CA) showed potent activity against melanoma in our previous study, and the structure of unsaturated aldehydes is envisaged to play a role. Nevertheless, its limited drug availability restricts its clinical application. Therefore, a series of CA analogues were synthesized to evaluate their anti-melanoma activities across various melanoma cell lines. These compounds were also tested for their toxicity against the different normal cell lines. The compound with the most potential, CAD-14, exhibited potent activity against the A375, A875 and SK-MEL-1 cells, with IC50 values of 0.58, 0.65, and 0.82 µM, respectively. A preliminary molecular mechanism study of CAD-14 indicated that it could inhibit the p38 pathway to induce apoptosis, and suppress tumor growth by inhibiting the expression of ENO1. Furthermore, an acute toxicity study depicted that CAD-14 has better safety and tolerability than CA in vivo. These findings indicate that CAD-14 might be a lead compound for exploring effective anti-melanoma drugs.

Optimal concentration of ropivacaine for brachial plexus blocks in adult patients undergoing upper limb surgeries: a systematic review and meta-analysis.

Aim of the Study: Brachial plexus block (BPB) is widely used for patients undergoing upper limb surgeries. Ropivacaine is the most commonly used local anesthetic for BPB. This study aimed to identify the optimal ropivacaine concentration for BPB in adult patients undergoing upper limb surgeries. Materials and Methods: PubMed, Embase, the Cochrane Library, and Web of Science were searched to identify randomized controlled trials (RCTs) that compared the effects of different concentrations of ropivacaine for BPB in adult patients undergoing upper limb surgeries. The primary outcomes were the onset time of sensory and motor block. RevMan 5.4 software was used for analysis. The GRADE approach was used to assess evidence quality. Results: Nine studies involving 504 patients were included. Compared to 0.5% ropivacaine, 0.75% ropivacaine shortened the onset time of sensory (WMD, -2.54; 95% CI; -4.84 to -0.24; <0.0001, moderate quality of evidence) and motor blockade (WMD, -2.46; 95% CI, -4.26 to -0.66; p = 0.01; moderate quality of evidence). However, 0.5% and 0.75% ropivacaine provided similar duration time of sensory (WMD, -0.07; 95% CI, -0.88 to 0.74; p = 0.81; high quality of evidence) and motor blockade (WMD, -0.24; 95% CI, -1.12 to 0.65; p = 0.55; high quality of evidence), as well as time to first request for oral analgesia (WMD, -1.57; 95% CI, -3.14 to 0.01; p = 0.5; moderate quality of evidence). Conclusion: Moderate-quality evidence suggested that, in terms of the onset time of sensory and motor blockade, 0.75% ropivacaine is a preferred concentration for BPB in upper limb surgeries. Systematic Review Registration: identifier CRD42023392145.

Aggregate Size Modulates the Oil/Water Interfacial Behavior of Myofibrillar Proteins: Toward the Thicker Interface Film and Disulfide Bond.

Myofibrillar protein (MP) aggregate models have been established to elucidate the correlation between their aggregate sizes and interfacial properties. The interfacial layer thickness was measured by the polystyrene latex method and quartz crystal microbalance with dissipation measurement. Interfacial conformations were then characterized in situ (front-surface fluorescence spectroscopy) and ex situ (reactive sulfhydryl group and secondary structure measurement following MP displacement). The viscoelasticity of the interfacial film and its resistance to surfactant-induced competitive displacement were reflected by the dilatational rheology and dynamic interfacial tension with the bulk phase exchange. Finally, we compared the findings of competitive displacement before/after adding a sulfhydryl-blocking agent, N-ethylmaleimide, to highlight the role of S-S linkage on interfacial film formation and stability. We substantiated that the aggregate size of the MP governed their interfacial properties. Small-sized aggregates exhibited more ordered secondary structures on the oil-water interface, which was conducive to the adsorption ratio of the protein and the adsorption dynamics. Although larger aggregates lowered the diffusion rate during interfacial film formation, they allowed the thicker and more viscoelastic interfacial film to be constructed afterward through more disulfide bond formation, resulting in greater resistance to surfactant-induced competitive displacement.

Circulating biomarkers in perioperative management of cancer patients.

Owing to the advances in surgical technology, most solid tumours can be controlled by surgical excision. The priority should be tumour control, while some routine perioperative management might influence cancer progression in an unnoticed way. Moreover, it is increasingly recognized that effective perioperative management should include techniques to improve postoperative outcomes. These influences are elucidated by the different functions of circulating biomarkers in cancer patients. Here, circulating biomarkers with two types of clinical functions were reviewed: (i) circulating biomarkers for cancer progression monitoring, for instance, those related to cancer cell malignancy, tumour microenvironment formation, and early metastasis, and (ii) circulating biomarkers with relevance to postoperative outcomes, including systemic inflammation, immunosuppression, cognitive dysfunction, and pain management. This review aimed to provide new perspectives for the perioperative management of patients with cancer and highlight the potential clinical translation value of circulating biomarkers in improving outcomes.

Big data analysis identified a telomere-related signature predicting the prognosis and drug sensitivity in lung adenocarcinoma.

Telomeres exert a critical role in chromosome stability and aberrant regulation of telomerase may result in telomeres dysfunction and genomic instability, which are involved in the occurrence of cancers. However, limited studies have been performed to fully clarify the immune infiltration and clinical significance of telomeres-related genes (TRGs) in lung adenocarcinoma (LUAD). The number of clusters of LUAD was determined by consensus clustering analysis. The prognostic signature was constructed and verified using TCGA and GSE42127 dataset with Least Absolute Shrinkage and Selection Operator cox regression analysis. The correlation between different clusters and risk-score and drug therapy response was analyzed using TIDE and IMvigor210 dataset. Using several miRNA and lncRNA related databases, we constructed a lncRNA-miRNA-mRNA regulatory axis. We identified 2 telomeres-related clusters in LUAD, which had distinct differences in prognostic stratification, TMB score, TIDE score, immune characteristics and signal pathways and biological effects. A prognostic model was developed based on 21 TRGs, which had a better performance in risk stratification and prognosis prediction compared with other established models. TRGs-based risk score could serve as an independent risk factor for LUAD. Survival prediction nomogram was also developed to promote the clinical use of TRGs risk score. Moreover, LUAD patients with high risk score had a high TMB score, low TIDE score and IC50 value of common drugs, suggesting that high risk score group might benefit from receiving immunotherapy, chemotherapy and target therapy. We also developed a lncRNA KCNQ1QT1/miR-296-5p/PLK1 regulatory axis. Our study identified 2 telomeres-related clusters and a prognostic model in LUAD, which could be helpful for risk stratification, prognosis prediction and treatment approach selection.

A novel antimycin analogue antimycin A2c, derived from marine Streptomyces sp., suppresses HeLa cells via disrupting mitochondrial function and depleting HPV oncoproteins E6/E7.

AIMS: Novel antimycin alkaloid antimycin A2c (AE) was isolated from the culture of a marine derived Streptomyces sp. THS-55. We elucidated its chemical structure by extensive spectra and clarified the specific mechanism in HPV infected-cervical cancer. MATERIALS AND METHODS: Colony formation assay, cell cycle analysis, hoechst 33342 staining assay, et.al were used to detect the inhibitory effect of AE on cervical cancer cells. Meanwhile, flow cytometry, western blotting, immunoprecipitation, RNA interference and molecular docking were used to analyze the mechanism of AE. KEY FINDINGS: AE exhibited potent cytotoxicity in vitro against HPV-transformed cervical cancer HeLa cell line. AE inhibited the proliferation, arrested cell cycle distribution, and triggered caspase dependent apoptosis in HeLa cells. Further studies revealed AE-induced apoptosis is mediated by the degradation of E6/E7 oncoproteins. Molecular mechanic investigation showed that AE degraded the levels of E6/E7 oncoproteins through reactive oxygen (ROS)-mediated ubiquitin-dependent proteasome system activation, and the increased ROS generation was due to the disruption of the mitochondrial function. SIGNIFICANCE: This present work revealed that this novel marine derived antimycin alkaloid could target the mitochondria and subsequently degrade HPV E6/E7 oncoproteins, and have potential application in the design and development of lead compound for cervical cancer cells, as well as the development for tool compounds to dissect E6/E7 functions.

Cinnamaldehyde induces apoptosis and enhances anti-colorectal cancer activity via covalent binding to HSPD1.

Colorectal cancer (CRC) is a common malignant tumor with high morbidity and mortality rates worldwide. Although surgical resection and adjuvant radiotherapy/chemotherapy are the mainstays of CRC treatment, the efficacy is unsatisfactory due to several limitations, including high drug resistance. Accordingly, there is a dire need for new drugs or a novel combination approach to treat this patient population. Herein, we found that cinnamaldehyde (CA) could exert an antitumor effect in HCT-116 cell lines. Target fishing, molecular imaging, and live-cell tracing using an alkynyl-CA probe revealed that the heat shock 60 kDa protein 1 (HSPD1) protein was the target of CA. The covalent binding of CA with HSPD1 altered its stability. Furthermore, our results demonstrated that CA could induce cell apoptosis by inhibiting the PI3K/Akt signaling pathway and enhanced anti-CRC activity both in vitro and in vivo. Meanwhile, CA combined with different chemotherapeutic agents was beneficial to patients resistant to anti-CRC drug therapy.

Simultaneous and Sensitive Detection of Three Pesticides Using a Functional Poly(Sulfobetaine Methacrylate)-Coated Paper-Based Colorimetric Sensor.

Chlorpyrifos (CHL), profenofos (PRO) and cypermethrin (CYP) are widely used in combination to increase crop yields. However, these three pesticides can cause serious harm to human health and do not easily degrade. In this study, a novel visible paper sensor has been prepared successfully and different colorimetric reactions were utilized to detect the three pesticides simultaneously. The sensor was constructed by grafting a zwitterionic polymer onto a cellulose filter (CF) and placing it on a glass surface modified with PDMS. The branch shape was designed to form multiple detection areas, which were modified with specific pesticides and corresponding chromogenic reagents. The as-prepared colorimetric platform exhibited high sensitivity, a short detection time, a good linear response and a low detection limit (LOD) for the three pesticides (chlorpyrifos: y = 46.801 - 1.939x, R2 = 0.983, LOD = 0.235 mg/L; profenofos: y = 40.068 + 42.5x, R2 = 0.988, LOD = 4.891 mg/L; cypermethrin: y = 51.993 + 1.474x, R2 = 0.993, LOD = 4.053 mg/L). The comparison of the results obtained by the proposed paper sensor and those obtained by spectrophotometry further revealed the stability and reliability of the paper sensor. In particular, the color intensity of the interaction between the pesticides and coloring agents could be directly observed by the human eye. The consistency of the colorimetric/optical assay was proven in real target pesticide samples. Thus, this sensing strategy provides a portable, cost-effective, accurate and visualized paper platform, which could be suitable for application in the fruit and vegetable industry for monitoring CHL, PRO and CYP in parallel.

Deep Neuromuscular Block for Endolaryngeal Surgery: A Systematic Review and Meta-Analysis.

OBJECTIVES: To determine the safety and efficacy of deep neuromuscular block (NMB) for endolaryngeal surgery. DATA SOURCES: PubMed, Web of Science, Cochrane Library, Ovid Medline, Embase, China National Knowledge Infrastructure, Wanfang, VIP databases, and trial registry database. METHODS: Inclusion criteria followed the PICOS principles: Participants, adults undergoing endolaryngeal surgery; Intervention, deep NMB performed during the surgery; Control, no-deep NMB performed; Outcomes, primary outcome: the incidence of clinically acceptable surgical conditions. SECONDARY OUTCOME: the incidence of intraoperative complications (including vocal fold movement and coughing) and total incidence of postoperative complications [including postoperative residual curarization (PORC), postoperative sore throat (POST), and postoperative nausea and vomiting (PONV)]. Study design, randomized controlled trials (RCTs). Duplicate publications, editorials, letters, abstracts, and reviews were excluded. RESULTS: Four articles with 242 patients were identified for analysis. The results indicated that compared with no-deep NMB, deep NMB provides a higher incidence of clinically acceptable surgical conditions (98.36% vs. 76.67%; relative ratio [RR] = 1.29, 95% CI: 1.07-1.56), a lower incidence of intraoperative complications (10.83% versus 37.16%; RR = 0.32; 95% CI: 0.21-0.49) (lower incidence of vocal fold movement [1.85% vs. 34%; RR = 0.08, 95% CI: 0.02-0.41] and coughing [15.53% vs. 38.78%; RR = 0.42, 95% CI: 0.27-0.66]). There were no differences in the overall incidence of postoperative complications (RR = 2.10, 95% CI: 0.12-36.40). CONCLUSIONS: Based on current published evidence, deep NMB provides better surgical conditions with a higher incidence of clinically acceptable surgical conditions and a lower incidence of intraoperative complications (lower incidence of vocal fold movement and coughing) without increasing the overall incidence of postoperative complications. LEVEL OF EVIDENCE: 1 Laryngoscope, 133:2055-2065, 2023.

The role of serum markers PAPP-A ß-hCG, AFP, and uE3 in predicting the risk of preeclampsia in early, middle, and late pregnancy.

BACKGROUND: Preeclampsia (PE) has adverse effects on pregnant women, fetuses, and newborns [1], and accounts for 3%-10% of pregnancy-related diseases globally. OBJECTIVE: This study aimed to screen a series of prenatal markers (pregnancy-associated plasma protein [PAPP-A], ß-human chorionic gonadotropin [ß-hCG], alpha fetoprotein [AFP], and estriol [uE3]) to establish a risk model and evaluate the diagnostic values of the markers for predicting PE. METHODS: Sixty-five pregnant women were enrolled in this study. They were divided into two groups containing healthy pregnant women (n= 51, the non-PE group) and pregnant women with PE (n= 14, the PE group). According to the stage of pregnancy, the pregnant women in each group were divided into early, middle, and late pregnancy groups for statistical analysis. The levels of PAPPA-A ß-hCG, AFP, and uE3 were compared among these groups. Then, a risk model was established, and PE was diagnosed using receiver operating characteristic (ROC) curve results. RESULTS: In the early pregnancy group, the differences in the levels of PAPP-A, AFP, and uE3 between the PE and non-PE groups were statistically significant (P< 0.001, P= 0.029, and P= 0.033, respectively), while the difference in the single remaining marker was not statistically significant. A ROC curve analysis revealed that in early pregnancy, the sensitivity and specificity of PAPP-A were 76.5% and 71.4%, respectively, and the sensitivity and specificity of ß-hCG were 82.4% and 57.1%, respectively. The sensitivity and specificity of the combination of the two markers for diagnosing PE were 86.3% and 57.1%, respectively. CONCLUSION: This study demonstrated that the combination of PAPP-A and ß-hCG has diagnostic value for PE in pregnant women. Accordingly, we should formulate innovative PE screening strategies to target the prevention of PE and create important conditions for predictive and preventive personalized medical treatments.

Genetic liability for diet-derived circulating antioxidants, oxidative stress, and risk of osteoarthritis: a Mendelian randomization study.

Background: Although well-documented, the causal relationships between diet-derived circulating antioxidants, oxidative stress, and osteoarthritis (OA) are equivocal. The objective of this study is to employ two-sample Mendelian randomization (MR) to investigate possible causal relationships among dietary-derived circulating antioxidants, oxidative stress damage indicators, and OA risk. Methods: Single-nucleotide polymorphisms for diet-derived circulating antioxidants (ascorbate, ß-carotene, lycopene, retinol, and α-and γ-tocopherol), assessed as absolute levels and metabolites, as well as oxidative stress injury biomarkers (GSH, GPX, CAT, SOD, albumin, and total bilirubin), were retrieved from the published data and were used as genetic instrumental variables. Summary statistics for gene-OA associations were obtained from publicly available and two relatively large-scale GWAS meta-analyses to date. The inverse-variance weighting method was utilized as the primary MR analysis. Moreover, multivariable MR was used to determine if mediators (BMI and smoking) causally mediated any connection. Furthermore, for each exposure, MR analyses were conducted per outcome database and then meta-analyzed. Results: Genetically predicted absolute retinol level was causally associated with hip OA risk [odds ratios (ORs) = 0.40, 95% confidence interval (CI) = 0.24-0.68, FDR-corrected p = 0.042]. Moreover, genetically predicted albumin level was causally associated with total OA risk (OR = 0.80, 95% CI = 0.75-0.86, FDR-corrected p = 2.20E-11), as well as the risk of hip OA (OR = 0.75, 95% CI = 0.68-0.84, FDR-corrected p = 1.38E-06) and knee OA (OR = 0.82, 95% CI = 0.76-0.89, FDR-corrected p = 4.49E-06). In addition, MVMR confirmed that the effect of albumin on hip OA is independent of smoking initiation, alcoholic drinks per week, and moderate-to-vigorous physical activity levels but may be influenced by BMI. Conclusion: Evidence from our study supports a potentially protective effect of high levels of retinol and albumin on OA risk.

Carbothermal Synthesis of Sludge Biochar Supported Nanoscale Zero-Valent Iron for the Removal of Cd2+ and Cu2+: Preparation, Performance, and Safety Risks.

The practical application of nanoscale zero-valent iron (NZVI) is restricted by its easy oxidation and aggregation. Here, sludge biochar (SB) was used as a carrier to stabilize NZVI for Cd2+ and Cu2+ removal. SB supported NZVI (SB-NZVI) was synthesized using the carbothermic method. The superior preparation conditions, structural characteristics, and performance and mechanisms of the SB-NZVI composites for the removal of Cd2+ and Cu2+ were investigated via batch experiments and characterization analysis. The optimal removal capacities of 55.94 mg/g for Cd2+ and 97.68 mg/g for Cu2+ were achieved at a Fe/sludge mass ratio of 1:4 and pyrolysis temperature of 900 °C. Batch experiments showed that the SB-NZVI (1:4-900) composite had an excellent elimination capacity over a broad pH range, and that weakly acidic to neutral solutions were optimal for removal. The XPS results indicated that the Cd2+ removal was mainly dependent on the adsorption and precipitation/coprecipitation, while reduction and adsorption were the mechanisms that play a decisive role in Cu2+ removal. The presence of Cd2+ had an opposite effect on the Cu2+ removal. Moreover, the SB-NZVI composites made of municipal sludge greatly reduces the leaching toxicity and bio-availability of heavy metals in the municipal sludge, which can be identified as an environmentally-friendly material.

6-Shogaol Exhibits a Promoting Effect with Tax via Binding HSP60 in Non-Small-Cell Lung Cancer.

Non-small-cell lung cancer (NSCLC) is a prevalent malignant tumor with high morbidity and mortality rates worldwide. Although surgical resection, adjuvant radiotherapy/chemotherapy, and targeted molecular therapy are the cornerstones of NSCLC treatment, NSCLC is associated with high recurrence rates and drug resistance. This study analyzed the potential targets and pathways of 6-Shogaol (6-SH) in NSCLC, showing that 6-SH binds to heat-shock 60 kDa protein (HSP60) in A549 cells, induces cell apoptosis, and arrests the cell cycle possibly by disrupting the mitochondrial function. HSP60 was identified as the target of 6-SH and 6-SH-induced HSP60 degradation which was mediated by the proteasome. The binding of 6-SH with HSP60 altered its stability, inhibited the ERK, Stat3, PI3K, Akt, and mTOR signaling pathways, and Tax acted synergistically with 6-SH, indicating that 6-SH could be developed as a potential therapeutic agent for an NSCLC treatment.

Interleukin-17 as a potential therapeutic target for chronic pain.

Chronic pain remains to be a clinical challenge and is recognized as a major health problem with varying impacts on quality of life. Currently, the first-line therapy for chronic pain is opioids, which are often accompanied by unwanted psychoactive side effects. Thus, new and effective treatments for chronic pain are urgently needed and eagerly pursued. Inflammatory cytokines, especially interleukin-17 (IL-17), are reportedly potential therapeutic targets owing to their pivotal role in chronic pain from the neuroinflammation perspective. Recently, substantial evidence confirmed that IL-17 and IL-17 receptors (IL-17Rs) were increased in neuropathic, inflammatory, and cancer pain models. Notably, IL-17/IL-17R antibodies also reportedly relieve or cure inflammatory- and pain-related diseases. However, existing studies have reported controversial results regarding IL-17/IL-17Rs as potential therapeutic targets in diverse animal models of chronic pain. In this review, we present a summary of published studies and discuss the evidence, from basic to clinical to research, regarding the role and mechanism of action between IL-17 and diverse kinds of chronic pain in animal models and clinical patients. Furthermore, we evaluated IL-17-based therapy as a potential therapeutic strategy for inflammatory- and pain-related disease. Importantly, we also discussed clinical trials of IL-17/IL-17R targeting monoclonal antibodies. Overall, we found that IL-17 is a potential therapeutic target for chronic pain from the perspective of neuroinflammation.

Myocarditis complicated by massive right ventricular thrombus and extensive pulmonary embolism: A case report.

An intracardiac thrombus may develop as a consequence of myocarditis, and in rare cases, a dominantly right ventricular thrombus develops, which may impair cardiac function and even cause life-threatening cardiovascular events. We report a 24-year-old man presented with recurrent episodes of palpitation and precordial discomfort after catching a cold 2 months ago. Transthoracic echocardiography (TTE) and computed tomography pulmonary angiogram (CTPA) revealed a mass attached to the apex of the right ventricle and extensive bilateral pulmonary artery emboli. There was no indication where the thrombi originated from in this young patient without any underlying disease except myocarditis. Pulmonary endarterectomy and embolectomy of pulmonary arteries and right ventricle were performed. Postoperative pathological results confirmed the presence of fibrinous necrosis and hemosiderin deposition. The formation of an intraventricular thrombus is closely related to myocarditis, which can affect individuals of all ages, but especially young people. Thus, patients with myocarditis should be closely monitored and followed up because of the increased risk of extensive thrombosis.