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Optically-encoded probes have great potential for applications in the fields of biosensing and imaging. By employing specific encoding methods, these probes enable the detection of multiple target molecules and high-resolution imaging within the same sample. Among the various encoding methods, surface-enhanced Raman scattering (SERS) spectral encoding stands out due to its extremely narrow linewidth. Compared to fluorescence spectral encoding, SERS encoding significantly reduces crosstalk between adjacent peaks, thereby achieving a larger encoding capacity and enabling multi-channel parallel analysis. This article presents the design and construction of two novel sets of SERS-encoded probes based on noble metal core-shell nanostructures. Two different encoding strategies are successfully applied to encode the SERS spectra of the probes: 1D encoding based on the wavenumber of characteristic peaks in the SERS spectrum, and 2D encoding combining both wavenumber and intensity of characteristic peaks in the SERS spectrum. In addition, this study also demonstrates the potential application of 1D encoded probes in cell sorting. These studies verify the feasibility of applying these two encoding methods to SERS core-shell probes and provide new insights into the construction of optically encoded probes., (© 2024 Wiley‐VCH GmbH.)

Objective: To assess the efficacy and safety of corticosteroids for the management of pediatric sepsis and septic shock., Data Sources: Ovid MEDLINE, Ovid Embase, CENTRAL, Web of Science (Core Collection) and China National Knowledge Infrastructure were systematically searched up to September 2023. Preprint servers, clinical trial registries and the reference sections of previous reviews were hand-searched., Study Selection: Randomized controlled trials that enrolled pediatric sepsis, septic shock or systemic inflammatory response syndrome patients, compared the use of corticosteroid regimens against standard sepsis care and reported eligible outcomes were included. Title/abstract and full-text screening were conducted in-duplicate., Data Extraction: Eligible articles were extracted using a standardized form in-duplicate. Outcomes extracted include mortality incidence, hospital and pediatric intensive care unit length of stay, duration of shock, incidence of adverse events and serious adverse events and incidence of corticosteroid-related adverse events. The risk of bias was assessed using the Revised Cochrane Risk of Bias Tool for Assessing Randomized Trials., Data Synthesis: Random-effects meta-analyses were conducted, and the quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations approach. Sixteen randomized controlled trials (N = 973) were included. Corticosteroid use may be associated with reduced mortality risks (risk ratio: 0.65, 95% CI: 0.50-0.85), shorter length of hospital stay (MD: -3.76 days, 95% CI: -6.66 to -0.86), and shorter pediatric intensive care unit length of stay (MD -2.34 days, 95% CI: -3.14 to -1.53 days). Corticosteroid use may be associated with gastrointestinal bleeding but not a higher risk of secondary infection. No studies reported on serious adverse events. All findings were based on low to very low quality of evidence., Conclusions: While corticosteroids show promise for managing pediatric sepsis and septic shock, the question of how to select the best candidate and the most optimal regimen remains unanswered. Future trials need to focus on assessing corticosteroid-related adverse events and stratifying patient inclusion by sepsis subphenotypes., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Coronavirus disease 2019 (COVID-19) has been a great concern since 2019. Patients with myasthenia gravis (MG) may be at higher risk of COVID-19 and a more severe disease course. We examined the associations between COVID-19 and MG., Methods: This single-center retrospective cohort study involved 134 patients who were diagnosed with MG from June 2020 to November 2022 and followed up until April 2023. They were divided into a COVID-19 group and non-COVID-19 group. Logistic regression analysis was used to detect factors potentially associating COVID-19 with MG., Results: Of the 134 patients with MG, 108 (80.6%) had COVID-19. A higher number of comorbidities was significantly associated with an increased risk of COVID-19 (p = 0.040). A total of 103 patients (95.4%) had mild/moderate COVID-19 symptoms, and 4 patients (3.7%) were severe/critical symptoms (including 2 deaths). Higher age (p = 0.036), use of rituximab (p = 0.037), tumors other than thymoma (p = 0.031), Hashimoto's thyroiditis (p = 0.011), more comorbidities (p = 0.002), and a higher baseline MG activities of daily living (MG-ADL) score (p = 0.006) were risk factors for severe COVID-19 symptoms. The MG-ADL score increased by ≥ 2 points in 16 (15.7%) patients. Dry cough and/or expectoration (p = 0.011), use of oral corticosteroids (p = 0.033), and use of more than one kind of immunosuppressant (p = 0.017) were associated with the increase of the post-COVID-19 MG-ADL score., Conclusion: Most patients with MG have a mild course of COVID-19. However, patients with older age, many comorbidities, a high MG-ADL score, and use of a variety of immunosuppressants during COVID-19 may be more prone to severe symptoms., (© 2024. Fondazione Società Italiana di Neurologia.)

Introduction: Solid organ transplant (SOT) recipients can experience bone loss caused by underlying conditions and the use of immunosuppressants. As a result, SOT recipients are at risk for decreased bone mineral density (BMD) and increased fracture incidences. We propose a network meta-analysis (NMA) that incorporates all available randomized control trial (RCT) data to provide the most comprehensive ranking of anti-osteoporotic interventions according to their ability to decrease fracture incidences and increase BMD in SOT recipients., Methods: We will search MEDLINE, EMBASE, Web of Science, CINAHL, CENTRAL and CNKI for relevant RCTs that enrolled adult SOT recipients, assessed anti-osteoporotic therapies, and reported relevant outcomes. Title and full-text screening as well as data extraction will be performed in-duplicate. We will report changes in BMD as weighted or standardized mean differences, and fracture incidences as risk ratios. SUCRA scores will be used to provide rankings of interventions, and quality of evidence will be examined using RoB2 and CINeMA., Discussions: To our knowledge, this systematic review and NMA will be the most comprehensive quantitative analysis regarding the management of bone loss and fractures in SOT recipients. Our analysis should be able to provide physicians and patients with an up-to-date recommendation for pharmacotherapies in reducing incidences of bone loss and fractures associated with SOT. The findings of the NMA will be disseminated in a peer-reviewed journal., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Deng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

To enhance our comprehension of the fundamental mechanisms driving tumor metabolism and metastasis, it is essential to dynamically monitor intratumoral lipid droplet (LD) and collagen processes in vivo. Traditional LD analysis in tumors predominantly relies on observations of in vitro cells or tissue slices, which unfortunately hinder real-time insights into the dynamic behavior of LDs during in vivo tumor progression. In this study, we developed a dual-modality imaging technique that combines coherent anti-Stokes Raman scattering (CARS) and second-harmonic generation (SHG) microscopy for in vivo monitoring of tumor LDs and collagen alterations, assisted by a murine breast cancer 4T1 cell-based dorsal skinfold window. Specifically, we accomplished real-time observations and quantitative analysis of the LD size, density, and collagen alignment within living tumors through CARS/SHG imaging. Additionally, our findings demonstrate that real-time LD monitoring provides a valuable means of assessing the efficacy of anticancer drugs in vivo. We evaluated the impact of adipose activators on lipid metabolism, oxidative stress, and tumor suppression by monitoring changes in LD size and density. Overall, this study highlights the potential of dual-modality CARS/SHG microscopy as a sensitive and flexible tool for antitumor therapeutic strategies.

Large language models, like ChatGPT and Bard, have potential clinical applications due to their ability to generate conversational responses and encode medical knowledge. However, their clinical adoption faces challenges including hallucinations, lack of transparency, and lack of consistency. Ethicolegal concerns surrounding patient consent, legal liability, and data privacy further complicate matters. Despite their promise, an optimistic but cautious approach is essential for the safe integration of large language models into clinical settings.

Introduction: This systematic review aimed to assess the efficacy and safety of hydrocortisone, ascorbic acid, and thiamine (HAT) combination therapy in patients with sepsis and septic shock., Methods: We conducted a database search in MEDLINE, Embase, CENTRAL, Web of Science, and CNKI for randomised controlled trials (RCTs) comparing HAT against placebo/standard of care or against hydrocortisone in sepsis/septic shock patients. Outcomes included mortality, ICU/hospital length of stay (LOS), vasopressor durations, mechanical ventilation durations, change in SOFA at 72 h, and adverse events. RCT results were pooled in random-effects meta-analyses. Quality of evidence was assessed using GRADE., Results: Fifteen RCTs (N = 2,594) were included. At 72 h, HAT reduced SOFA scores from baseline (mean difference [MD] -1.16, 95% confidence interval [CI]: -1.58 to -0.74, I2 = 0%) compared to placebo/SoC, based on moderate quality of evidence. HAT also reduced the duration of vasopressor use (MD -18.80 h, 95% CI: -23.67 to -13.93, I2 = 64%) compared to placebo/SoC, based on moderate quality of evidence. HAT increased hospital LOS (MD 2.05 days, 95% CI: 0.15-3.95, I2 = 57%) compared to placebo/SoC, based on very low quality of evidence. HAT did not increase incidence of adverse events compared to placebo/SoC., Conclusions: HAT appears beneficial in reducing vasopressor use and improving organ function in sepsis/septic shock patients. However, its advantages over hydrocortisone alone remain unclear. Future research should use hydrocortisone comparators and distinguish between sepsis-specific and comorbidity- or care-withdrawal-related mortality., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

BACKGROUND. Pure ground-glass nodules (pGGNs) on chest CT representing invasive adenocarcinoma (IAC) warrant lobectomy with lymph node resection. For pGGNs representing other entities, close follow-up or sublobar resection without node dissection may be appropriate. OBJECTIVE. The purpose of this study was to develop and validate an automated deep learning model for differentiation of pGGNs on chest CT representing IAC from those representing atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS), and minimally invasive adenocarcinoma (MIA). METHODS. This retrospective study included 402 patients (283 women, 119 men; mean age, 53.2 years) with a total of 448 pGGNs on noncontrast chest CT that were resected from January 2019 to June 2022 and were histologically diagnosed as AAH ( n = 29), AIS ( n = 83), MIA ( n = 235), or IAC ( n = 101). Lung-PNet, a 3D deep learning model, was developed for automatic segmentation and classification (probability of IAC vs other entities) of pGGNs on CT. Nodules resected from January 2019 to December 2021 were randomly allocated to training ( n = 327) and internal test ( n = 82) sets. Nodules resected from January 2022 to June 2022 formed a holdout test set ( n = 39). Segmentation performance was assessed with Dice coefficients with radiologists' manual segmentations as reference. Classification performance was assessed by ROC AUC and precision-recall AUC (PR AUC) and compared with that of four readers (three radiologists, one surgeon). The code used is publicly available (https://github.com/XiaodongZhang-PKUFH/Lung-PNet.git). RESULTS. In the holdout test set, Dice coefficients for segmentation of IACs and of other lesions were 0.860 and 0.838, and ROC AUC and PR AUC for classification as IAC were 0.911 and 0.842. At threshold probability of 50.0% or greater for prediction of IAC, Lung-PNet had sensitivity, specificity, accuracy, and F1 score of 50.0%, 92.0%, 76.9%, and 60.9% in the holdout test set. In the holdout test set, accuracy and F1 score ( p values vs Lung-PNet) for individual readers were as follows: reader 1, 51.3% ( p = .02) and 48.6% ( p = .008); reader 2, 79.5% ( p = .75) and 75.0% ( p = .10); reader 3, 66.7% ( p = .35) and 68.3% ( p < .001); reader 4, 71.8% ( p = .48) and 42.1% ( p = .18). CONCLUSION. Lung-PNet had robust performance for segmenting and classifying (IAC vs other entities) pGGNs on chest CT. CLINICAL IMPACT. This automated deep learning tool may help guide selection of surgical strategies for pGGN management.

This systematic review and meta-analysis of randomised controlled trials (RCTs) aimed to evaluate the efficacy, safety, and tolerability of fluvoxamine for the outpatient management of COVID-19. We conducted this review in accordance with the PRISMA 2020 guidelines. Literature searches were conducted in MEDLINE, EMBASE, International Pharmaceutical Abstracts, CINAHL, Web of Science, and CENTRAL up to 14 September 2023. Outcomes included incidence of hospitalisation, healthcare utilization (emergency room visits and/or hospitalisation), mortality, supplemental oxygen and mechanical ventilation requirements, serious adverse events (SAEs) and non-adherence. Fluvoxamine 100 mg twice a day was associated with reductions in the risk of hospitalisation (risk ratio [RR] 0.75, 95% confidence interval [CI] 0.58-0.97; I 2  = 0%) and reductions in the risk of healthcare utilization (RR 0.68, 95% CI 0.53-0.86; I 2  = 0%). While no increased SAEs were observed, fluvoxamine 100 mg twice a day was associated with higher treatment non-adherence compared to placebo (RR 1.61, 95% CI 1.22-2.14; I 2  = 53%). In subgroup analyses, fluvoxamine reduced healthcare utilization in outpatients with BMI ≥30 kg/m 2 , but not in those with lower BMIs. While fluvoxamine offers potential benefits in reducing healthcare utilization, its efficacy may be most pronounced in high-risk patient populations. The observed non-adherence rates highlight the need for better patient education and counselling. Future investigations should reassess trial endpoints to include outcomes relating to post-COVID sequelaes. Registration: This review was prospectively registered on PROSPERO (CRD42023463829)., (© 2023 The Authors. Reviews in Medical Virology published by John Wiley & Sons Ltd.)

(R)-β-piperonyl-γ-butyrolactones are key building blocks for the synthesis of podophyllotoxin, which have demonstrated remarkable potential in cancer treatment. Baeyer-Villiger monooxygenases (BVMOs)-mediated asymmetric oxidation is a green approach to produce chiral lactones. While several BVMOs were able to oxidize the corresponding cyclobutanone, most BVMOs gave the (S) enantiomer while Cyclohexanone monooxygenase (CHMO) from Brevibacterium sp. HCU1 gave (R) enantiomer, but with a low enantioselectivity (75 % ee). In this study, we use a strategy called "focused rational iterative site-specific mutagenesis" (FRISM) at residues ranging from 6 Å from substrate. The mutations by using a restricted set of rationally chosen amino acids allow the formation of a small mutant library. By generating and screening less than 60 variants, we achieved a high ee of 96.8 %. Coupled with the cofactor regeneration system, 9.3 mM substrate was converted completely in a 100-mL scale reaction. Therefore, our work reveals a promising synthetic method for (R)-β-piperonyl-γ-butyrolactone with the highest enantioselectivity, and provides a new opportunity for the chem-enzymatic synthesis of podophyllotoxin., (© 2023 Wiley-VCH GmbH.)

Background: This retrospective study aimed to compare preferential manual bronchoplasty (PMB) and mechanical stapler closure (MSC) of the bronchial stump after 2-3 cm single-port (SP) video-assisted thoracoscopic surgery (VATS) lobectomy in patients with pathological T1 (pT1) stage lung cancer., Methods: Between January 2019 and March 2022, patients with pulmonary neoplasms who underwent 2-3 cm SP VATS lobectomy were retrospectively screened. After propensity-matched analysis, we compared perioperative outcomes and analyzed the safety and feasibility of PMB and MSC of the bronchial stump while performing VATS lobectomy., Results: In this study, 280 and 832 patients were enrolled in the PMB and MSC groups, respectively. Propensity score matching produced 280 pairs. The operation time was shorter in the PMB group, whereas the average number of lymph nodes dissected was higher in the PMB group. The conversion rate was significantly lower in the PMB group. The following were similar between the PMB and MSC groups, respectively: average blood loss volume, postoperative hospital stay, and chest tube removal time. Postoperatively, the incidence of atelectasis was significantly higher in the MSC group. As per subgroup analyses, PMB was associated with a shorter operation time in left and right upper lobectomies. Particularly in left upper lobectomy, PMB had more lymph node dissections and less conversion to open and postoperative atelectasis., Conclusions: In comparison with MSC of the bronchial stump, PMB showed better safety and feasibility in 2-3 cm SP VATS left and right superior lobectomies in patients with pT1 stage lung cancer., (© 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: The prognostic value of radical surgery (RS) and chemoradiotherapy (CRT) for cervical esophageal cancer (CEC) was estimated using the Surveillance, Epidemiology and End Results (SEER) database after 1:1 propensity score matching (PSM)., Methods: This retrospective study used SEER data of CEC patients between 2004 and 2015. The prognostic effects on cancer-specific survival (CSS) were evaluated using multivariate cox regression analysis following radical surgery or CRT before and after PSM. The subgroup analysis of CSS is carried out according to T stages., Results: A total of 440 patients met the eligibility criteria. Three hundred and fifty-six(80.9%)patients underwent chemoradiotherapy, and eighty-four (19.1%) patients underwent radical surgery. There were significant differences between patients of radical surgery and CRT groups with regard to the tumor grade, histology and N stage. After PSM, 80 matched pairs (A total of 160 patients) were selected. Multivariable cox regression analysis revealed no difference in the CSS of patients that underwent either radical surgery or CRT before [hazard ratio (HR): 0.955, 95% CI: 0.704-1.295, P = 0.766] and after PSM (HR: 0.767, 95% CI: 0.512-1.149, P = 0.198). Subgroup analysis revealed no significant difference in CSS between patients with radical surgery and CRT groups for all T stages (T 1-4, all P > 0.05)., Conclusions: This analysis revealed that the prognostic outcomes in patients with cervical esophageal cancer were comparable between radical surgery and CRT., (© 2023. The Author(s).)

The COVID-19 pandemic and its accompanying infection control measures introduced sudden and significant disruptions to the lives of children and adolescents around the world. Given the potential for negative impacts on the mental health of youths as a result of these changes, we conducted a systematic review and meta-analysis to examine the prevalence of depressive symptoms, anxiety symptoms, and sleep disturbances in children and adolescents during the pandemic. We searched major literature databases for relevant cross-sectional or longitudinal studies that included primary and secondary school students or children and adolescents ≤18 years of age. Prevalence values were extracted, logit-transformed, and pooled. Based on 191 included studies with 1,389,447 children and adolescents, we found the pooled prevalence of depressive symptoms, anxiety symptoms, and sleep disturbances to be 31%, 31%, and 42%, respectively. Age, grade levels, education levels, gender, geographical regions, and electronics use were correlated with the prevalence of mental health symptoms. The prevalence of mental health symptoms also increased with time, although signs of recovery and stabilization were also observed. Overall, the results from this review demonstrate the need for increased mental health research, monitoring, and intervention for children and adolescents during the current and future pandemics., (© 2022 New York Academy of Sciences.)

Background: Despite superior short-term outcomes, there is considerable debate about the oncological efficacy of the left approach esophagectomy for middle and lower squamous esophageal carcinoma (ESCC). A propensity score-matched retrospective study was conducted to evaluate the left approach's short- and long-term effects., Methods: We recorded data from patients with ESCC who underwent curative resection via the left or right approach between January 2010 and December 2015. Propensity score matching (PSM) was performed, and maximally selected rank statistics (MSRS) were utilized to determine the appropriate number of lymph nodes to resect during esophagectomy., Results: One hundred and forty-eight ESCC patients underwent esophagectomy via the right approach, and 108 underwent the left approach esophagectomy. After PSM, the left approach esophagectomy showed statistically significant superiority in operative time and time to oral intake, and there was a trend toward a shorter length of hospital stay. Fewer cervical, upper thoracic, and recurrent laryngeal nerve lymph nodes were harvested via the left approach than the right approach; the total number of lymph nodes harvested via the left and right approaches was similar. Similar long-term survival outcomes were achieved. MSRS suggested that at least 25 lymph nodes are needed to be resected during esophagectomy to improve survival in N0 patients., Conclusions: The left approach esophagectomy might facilitate postoperative recovery in patients with middle and lower ESCC. With adequate lymphadenectomy, the left approach esophagectomy might achieve similar long-term outcomes for middle and lower ESCC patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Qi, Huang, Liu, Lin and Li.)

PARP inhibitors can be used to treat solid tumors that often have mutations in important homologous recombination (HR) genes, such as BRCA1/2. While other kinds of tumors could also experience HR deficiencies, including those associated with lung cancer, there is little information on the frequency of these occurrences. Homologous recombination deficiency (HRD) was used to induce particular DNA aberration profiles and related transcriptome alterations. Their presence can identify whether an HR deficiency is present or absent in a particular tumor sample, even without observed HR gene changes. From whole-exome sequencing data in lung adenocarcinoma obtained from TCGA, we obtained several mutational signatures associated with HRD and determined that these HRD-associated mutational signatures are related to genomic installability. We then constructed a prediction model, which found that 11 genes associated with HRD scores could be used as predictors of survival outcomes in LUAD patients. These genes are related to PI3K-Akt, T cell receptors, and the Chemokine pathway. Other GEO datasets validated the survival prediction, which was independent of the PD1/PDL1 treatment. Collectively, our study provides transcriptome biomarkers of lung adenocarcinoma complementary to the HRD score and introduces a novel method of identifying prognostic biomarkers of immunotherapy., Competing Interests: Author DW is employed by ChosenMed Technology Co., Ltd., Beijing. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shang, Qi, Liu, Liu, Zhang, Wang and Huang.)

Aim: To evaluate the efficacy and safety of corticosteroids for treating hospitalized COVID-19 patients., Materials & Methods: Efficacy outcomes included time to negative SARS-CoV-2 tests, length of stay, duration and incidence of intensive unit care stay, incidence of mortality and duration and incidence of mechanical ventilation. Safety outcomes included the incidence of adverse events and severe adverse events, incidence of hyperglycemia and incidence of nosocomial infections., Results: Ninety-five randomized controlled trials (RCTs) and observational studies (n = 42,205) were included. Corticosteroids were associated with increased length of stay (based on RCT only), increased time to negative tests, decreased length of mechanical ventilation and increased odds of hyperglycemia., Conclusion: Corticosteroids should be considered in patients requiring mechanical ventilation, and glycemic monitoring may be needed when administering corticosteroids., (© 2022 Future Medicine Ltd.)

Background: Death-associated protein kinase (DAPK) has a strong function of tumor suppression involving apoptosis regulation, autophagy, and metastasis inhibition. Hypermethylation of CpG islands in DAPK gene promoter region is one of the important ways to inactivate this tumor suppressor gene, which might promote lung carcinogenesis. However, the clinicopathological significance of the DAPK promoter hypermethylation in lung cancer remains unclear. In this study, we performed a meta-analysis trying to estimate the clinicopathological significance of DAPK promoter hypermethylation in non-small cell lung cancer (NSCLC)., Methods: A detailed literature search for publications relevant to DAPK gene promoter methylation and NSCLC was made in PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, CSTJ, Wanfang databases, and SinoMed (CBM). The random-effects model and fixed-effects model were utilized to pool the relative ratio based on the heterogeneity test in the meta-analysis., Results: A total of 41 studies with 3348 patients were included. The frequency of DAPK methylation was significantly higher in NSCLC than in non-malignant control (odds ratio (OR) = 6.88, 95% confidence interval (CI):  4.17-11.35, P  < 0.00001). The pooled results also showed that DAPK gene promoter hypermethylation was significantly associated with poor prognosis for overall survival in patients with NSCLC (hazard ratio: 1.23, 95% CI:1.01-1.52, P  = 0.04). Moreover, DAPK gene promoter hypermethylation was significantly associated with squamous cell carcinoma (OR: 1.25, 95% CI: 1.01-1.54, P  = 0.04) and smoking behavior (OR: 1.42, 95% CI: 1.04-1.93, P  = 0.03) but not with TNM stage, tumor differentiation, age, or gender., Conclusion: DAPK promoter hypermethylation might be a candidate diagnostic and prognostic tumor marker for NSCLC.

A series of novel one-dimensional (1D) ZnS/MnS heteronanostructures were prepared by a multistep solution-solid-solid (SSS) growth method using [(C 4 H 9 ) 2 NCS 2 ] 2 Zn and [(C 4 H 9 ) 2 NCS 2 ] 2 Mn as the precursors and Ag 2 S as the catalyst. The composition of the 1D heteronanostructures could be effectively modulated by varying the addition sequence of the precursors, such as the Ag 2 S/MnS/ZnS and Ag 2 S/ZnS/MnS heteronanostructures, which were obtained through the successive addition of [(C 4 H 9 ) 2 NCS 2 ] 2 Zn and [(C 4 H 9 ) 2 NCS 2 ] 2 Mn precursors but in different sequences. Using the same Ag 2 S catalysts, the average diameter of the 1D ZnS/MnS heteronanostructures with multisegments of ZnS and MnS is located between that of ZnS nanorod in Ag 2 S/ZnS and that of MnS nanorod in Ag 2 S/MnS. This phenomenon could arise from the different cationic radii and lattice parameters of ZnS and MnS. The UV-vis absorbance of the 1D ZnS/MnS heteronanostructures could be attributed to the interband transitions of ZnS and MnS. These findings contribute to the rational synthesis of novel 1D semiconductor heteronanostructures with multicomponents and benefit the development of optoelectronic devices.

Nucleotides, which are important low-molecular-weight compounds present in organisms, are precursors of nucleic acids and participate in various regulatory and metabolic functions. Sensitive and valid methods for monitoring and determining nucleotides and nucleosides in different samples are urgently required. Due to the presence of numerous endogenous interferences in complex matrices and the high polarity of the molecules of the phosphate moiety, the determination of nucleotide content is challenging. This review summarizes the pretreatment and analysis methods of nucleotides in different samples. Advanced pretreatment methods, including different microextraction methods, solid-phase extraction based on novel materials, QuEChERS, are clearly displayed, and continuous progress which has been made in LC, LC-MS/MS and capillary electrophoresis methods are discussed. Moreover, the strengths and weaknesses of different methods are discussed and compared. Highlight:Advanced pretreatment and detection methods of nucleotides were critically reviewed.Microextraction technology was one of the trends of nucleotides pretreatment in the future.Applications of novel materials and supercritical fluid were highlighted.The evolution and advance of HRMS analyzers were in detailed.

Aim: To evaluate the efficacy and safety of lopinavir-ritonavir (LPV/r) therapy in treating hospitalized COVID-19 patients. Materials & methods: Data from randomized and observational studies were included in meta-analyses. Primary outcomes were length of stay, time for SARS-CoV-2 test conversion, mortality, incidence of mechanical ventilation, time to body temperature normalization and incidence of adverse events. Results: Twenty-four studies (n = 10,718) were included. LPV/r demonstrated no significant benefit over the control groups in all efficacy outcomes. The use of LPV/r was associated with a significant increase in the odds of adverse events. Conclusion: Given the lack of efficacy and increased incidence of adverse events, the clinical use of LPV/r in hospitalized COVID-19 patients is not recommended., (© 2022 Future Medicine Ltd.)

Background: The diagnostic value of six tumor markers was investigated and the appropriate combinations of those tumor markers to discriminate small cell lung cancer was explored., Methods: Patients suspected with lung cancer (1938) were retrospectively analyzed. Candidate tumor markers from carcinoembryonic antigen (CEA), squamous cell carcinoma-related antigen (SCC), cytokeratin 19 fragment 21-1 (CYFRA 21-1), neuron-specific enolase (NSE), tissue polypeptide antigen (TPA), and progastrin releasing peptide (ProGRP) were selected to construct a logistic regression model. The receiver operating characteristic curve was used for evaluating the diagnostic value of the tumor markers and the predictive model., Results: ProGRP had the highest positive rate (72.3%) in diagnosed small cell lung cancer, followed by neuron-specific enolase (68.3%), CYFRA21-1 (50.5%), carcinoembryonic antigen (45.5%), tissue polypeptide antigen (30.7%), and squamous cell carcinoma-related antigen (5.9%). The predictive model for small cell lung cancer discrimination was established, which yielded the highest area under the curve (0.888; 95% confidence interval: 0.846-0.929), with a sensitivity of 71.3%, a specificity of 95.0%, a positive predictive value of 49.0%, and a negative predictive value of 98.0%., Conclusions: Combining tumor markers can improve the efficacy for small cell lung cancer discrimination. A predictive model has been established in small cell lung cancer differential diagnosis with preferable efficacy.

The Daucus carota polysaccharides were extracted by hot water extraction and alcohol precipitation, and the phosphorylated and carboxymethylated derivatives were prepared. Their structures were characterized by FT-IR, NMR, and SEM. The antioxidant activities of Daucus carota polysaccharide were enhanced by phosphorylation. However, carboxymethylated Daucus carota polysaccharide was not as good as unmodified one., (© 021 John Wiley & Sons Ltd.)

Aims: To evaluate the efficacy and safety of hydroxychloroquine/chloroquine, with or without azithromycin, in treating hospitalized COVID-19 patients. Materials & methods: Data from randomized and observational studies were included in a random-effects meta-analysis. Primary outcomes included time to negative conversion of SARS-CoV-2 tests, length of stay, mortality, incidence of mechanical ventilation, time to normalization of body temperature, incidence of adverse events and incidence of QT prolongations. Results: Fifty-one studies (n = 61,221) were included. Hydroxychloroquine/chloroquine showed no efficacy in all primary efficacy outcomes, but was associated with increased odds of QT prolongations. Conclusion: Due to a lack of efficacy and increased odds of cardiac adverse events, hydroxychloroquine/chloroquine should not be used for treating hospitalized COVID-19 patients., (© 2021 Future Medicine Ltd.)

The COVID-19 pandemic and its accompanying infection control measures introduced significant disruptions to the routines of many higher education students around the world. It also deprived them of in-person counselling services and social support. These changes have put students at a greater risk of developing mental illness. The objective of this review is to assess the prevalence of depressive symptoms, anxiety symptoms and sleep disturbances in higher education students during the pandemic. A systematic search of English and Chinese databases was conducted current to January 1 st , 2021. The quality of included studies was evaluated using a modified Newcastle-Ottawa scale. Prevalence of depressive symptoms, anxiety symptoms and sleep disturbances were pooled using random-effects meta-analysis. Eighty-nine studies (n=1,441,828) were included. The pooled prevalence of depressive symptoms, anxiety symptoms, and sleep disturbances was 34%, 32% and 33%, respectively. The prevalence values differ based on geographical regions, diagnostic criteria, education level, undergraduate year of study, financial situation, living arrangements and gender. Overall, the prevalence of depressive symptoms and anxiety symptoms synthesized in this study was higher compared to pre-pandemic prevalence in similar populations. Evidently, mental health screening and intervention should be a top priority for universities and colleges during the pandemic., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Hyperalgesia, which often occurs in people suffering from alcohol use disorder, may drive excessive drinking and relapse. Emerging evidence suggests that the lateral habenula (LHb) may play a significant role in this condition. Previous research suggests that endocannabinoid signaling (eCBs) is involved in drug addiction and pain, and that the LHb contains core components of the eCBs machinery. We report here our findings in rats subjected to chronic ethanol vapor exposure. We detected a substantial increase in endocannabinoid-related genes, including Mgll and Daglb mRNA levels, as well as monoacylglycerol lipase (MAGL) protein levels, as well as a decrease in Cnr1 mRNA and type-1 cannabinoid receptor (CB1R) protein levels, in the LHb of ethanol-exposed rats. Also, rats withdrawing from ethanol exposure displayed hypersensitivity to mechanical and thermal nociceptive stimuli. Conversely, intra-LHb injection of the MAGL inhibitor JZL184, the fatty acid amide hydrolase inhibitor URB597, or the CB1R agonist WIN55,212-2 produced an analgesic effect, regardless of ethanol or air exposure history, implying that alcohol exposure does not change eCB pain responses. Intra-LHb infusion of the CB1R inverse agonist rimonabant eliminated the analgesic effect of these chemicals. Rimonabant alone elicited hyperalgesia in the air-, but not ethanol-exposed animals. Moreover, intra-LHb JZL184, URB597, or WIN55,212-2 reduced ethanol consumption in both homecages and operant chambers in rats exposed to ethanol vapor but not air. These findings suggest that LHb eCBs play a pivotal role in nociception and facilitating LHb eCBs may attenuate pain in drinkers.

Thin-film transistors (TFTs) have been widely used in the increasingly advanced field of displays. However, it remains a challenge for TFTs to overcome the poor subthreshold swing in the fast switching and high-speed applications. Here, we provide a solution to the above-mentioned challenge via supercritical dehydroxylation, which combines a low temperature, environmentally friendly supercritical fluid technology with a CaCl 2 treatment. An embedded structure of amorphous indium gallium zinc oxide (a-IGZO) TFTs with double-layer high-k dielectric containing Ta 2 O 5 and SiO 2 layers was first manufactured. The subthreshold swing of the fabricated TFTs treated with supercritical dehydroxylation was optimized to an ultra-low value of 72.7 mV dec -1 . Moreover, other key figures of merits including threshold voltage, on/off ratio and field effect mobility all improved after the supercritical dehydroxylation. The bandgap of the gate dielectric material increased due to the supercritical dehydroxylation verified by the current conduction mechanism. Besides, numerous material analyses further confirmed that owing to the supercritical dehydroxylation the dominant dehydration reactions can effectively repair the defects introduced in the device manufacture. The ultra-low subthreshold swing with optimized electrical performances can be achieved via the low-temperature supercritical dehydroxylation treatment, enabling its promising potential in realizing ultra-fast and low power electronics.

Background: Currently, there is no reliable method for predicting the prognosis of patients with large cell lung cancer (LCLC). The aim of this study was to develop and validate a nomogram model for accurately predicting the prognosis of patients with LCLC., Methods: LCLC patients, diagnosed from 2007 to 2009, were identified from the Surveillance, Epidemiology and End Results (SEER) database and used as the training dataset. Significant clinicopathologic variables (P<0.05) in a multivariate Cox regression were selected to build the nomogram. The performance of the nomogram model was evaluated by the concordance index (C-index), the area under the curve (AUC), and internal calibration. LCLC patients diagnosed from 2010 to 2016 in the SEER database were selected as a testing dataset for external validation. The nomogram model was also compared with the currently used American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging system (8 th edition) by using C-index and a decision curve analysis., Results: Eight variables-age, sex, race, marital status, T stage, N stage, M stage, and treatment strategy-were statistically significant in the multivariate Cox model and were selected to develop the nomogram model. This model exhibited excellent predictive performance. The C-index and AUC value were 0.761 [95% confidence interval (CI), 0.754 to 0.768] and 0.886 for the training dataset and 0.773 (95% CI, 0.765 to 0.781) and 0.876 for the testing dataset, respectively. This model also predicted three-year and five-year lung cancer-specific survival (LCSS) in both datasets with good fidelity. This nomogram model performs significantly better than the 8th edition AJCC TNM staging system, with a higher C-index (P<0.001) and better net benefits in predicting LCSS in LCLC patients., Conclusions: We developed and validated a prognostic nomogram model for predicting 3- and 5-year LCSS in LCLC patients with good discrimination and calibration abilities. The nomogram may be useful in assisting clinicians to make individualized decisions for appropriate treatment in LCLC., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tlcr-19-517b). The authors have no conflicts of interest to declare., (2021 Translational Lung Cancer Research. All rights reserved.)

Evidence from previous coronavirus outbreaks has shown that infected patients are at risk for developing psychiatric and mental health disorders, such as depression, anxiety, and sleep disturbances. To construct a comprehensive picture of the mental health status in COVID-19 patients, we conducted a systematic review and random-effects meta-analysis to assess the prevalence of depression, anxiety, and sleep disturbances in this population. We searched MEDLINE, EMBASE, PubMed, Web of Science, CINAHL, Wanfang Data, Wangfang Med Online, CNKI, and CQVIP for relevant articles, and we included 31 studies (n = 5153) in our analyses. We found that the pooled prevalence of depression was 45% (95% CI: 37-54%, I 2  = 96%), the pooled prevalence of anxiety was 47% (95% CI: 37-57%, I 2  = 97%), and the pooled prevalence of sleeping disturbances was 34% (95% CI: 19-50%, I 2  = 98%). We did not find any significant differences in the prevalence estimates between different genders; however, the depression and anxiety prevalence estimates varied based on different screening tools. More observational studies assessing the mental wellness of COVID-19 outpatients and COVID-19 patients from countries other than China are needed to further examine the psychological implications of COVID-19 infections., (© 2020 New York Academy of Sciences.)

Background: Traditional Chinese medicine Tongxinluo (TXL) has been widely used to treat coronary artery disease in China, since it could reduce myocardial infarct size and ischemia/reperfusion injury in both non-diabetic and diabetic conditions. It has been shown that TXL could regulate peroxisome proliferator activated receptor-α (PPAR-α), a positive modulator of angiopoietin-like 4 (Angptl4), in diabetic rats. Endothelial junction substructure components, such as VE-cadherin, are involved in the protection of reperfusion injury. Thus, we hypothesized cell-intrinsic and endothelial-specific Angptl4 mediated the protection of TXL on endothelial barrier under high glucose condition against ischemia/reperfusion-injury via PPAR-α pathway., Methods: Incubated with high glucose medium, the human cardiac microvascular endothelial cells (HCMECs) were then exposed to oxygen-glucose-serum deprivation (2 hours) and restoration (2 hours) stimulation, with or without TXL, insulin, or rhAngptl4 pretreatment., Results: TXL, insulin, and rhAngptl4 had similar protective effects on the endothelial barrier. TXL treatment reversed the endothelial barrier breakdown in HCMECs significantly as identified by decreasing endothelial permeability, upregulating the expression of JAM-A, VE-cadherin, and integrin-α5 and increasing the membrane location of VE-cadherin and integrin-α5, and these effects of TXL were as effective as insulin and rhAngptl4. However, Angptl4 knock-down with small interfering RNA (siRNA) interference and PPAR-α inhibitor MK886 partially abrogated these beneficial effects of TXL. Western blotting also revealed that similar with insulin, TXL upregulated the expression of Angptl4 in HCMECs, which could be inhibited by Angptl4 siRNA or MK886 exposure. TXL treatment increased PPAR-α activity, which could be diminished by MK886 but not by Angptl4 siRNA., Conclusion: These data suggest cell-intrinsic and endothelial-specific Angptl4 mediates the protection of TXL against endothelial barrier breakdown during oxygen-glucose-serum deprivation and restoration under high glucose condition partly via the PPAR-α/Angptl4 pathway.

The common long-armed octopus, Octopus minor, is an important component of systems and supports the local fisheries in the coastal areas of northern China. For the fishery management and artificial breeding, especially for the management of exclusive conservation reserves, its role in the ecosystem requires assessment. Therefore, the feeding intensity of O. minor was studied from April to July 2014 when females reaching ovary maturation, and prey composition was identified from stomach contents using a DNA barcoding method. Of the 172 sampled octopuses, 66 had stomach contents that were nearly digested into pulp. On the whole, the feeding intensity of octopus remained more or less the same during the first three months and significantly decreased in July. The changes of feeding intensity were different between females and males; in females, the intensity of feeding decreased from April to July; in case of males, however, the feeding activity increased from April to June and decreased thereafter. The feeding intensity of the females was extremely greater than that of the males. O. minor was a generalist predator and based on homology searches and phylogenetic analysis, a total of 10 different taxa were identified in the stomach contents. In terms of percent composition by frequency of occurrences (%N), fishes accounted for the most of the octopuses diet (50%), followed by cephalopod (25%), crustaceans (21.7%), annelid (1.7%) and nematode (1.7%). The families of Gobiidae and Octopodidae appeared in all months and Protunidae appeared in three months. The results confirmed that Gobiidae family (45.8%, by frequency of occurrences) was an important source of food during the time when females reaching ovarian maturation. From April to July, the observed cannibalism showed an increasing trend. Controlling and reducing fishing production of Gobiidae fishes in conservation area are recommended from April to June when female octopuses are actively feeding., Competing Interests: The authors have declared that no competing interests exist.

Background: It is common for patients with lung cancer to have concomitant coronary artery disease, some of them have underwent coronary stenting and accepted antiplatelet therapy. Whether antiplatelet agents should be continued in the perioperative period remains controversial, especially in patients requiring lung cancer resection with coronary artery stents. We reviewed the data of our institute to clarify the perioperative outcomes of this specific population., Methods: We retrospectively analyzed the data on patients who underwent pulmonary resection for lung cancer following coronary stent placement between January 2013 and September 2019 in the Department of Thoracic Surgery in Peking University First Hospital. All of them discontinued oral antiplatelet agents before operation at least 5 days. The primary outcomes were the cardiovascular morbidity and mortality in hospital., Results: 111 patients were identified and included in the analysis. The time intervals between stenting and lung surgery were 1-3 months, 3-12 months, and more than 12 months in 6.3%, 13.5% and 80.2% of the patients, respectively. Sublobectomy, lobectomy, biolobectomy, pneumonectomy and sleeve lobectomy were performed in 10.8%, 71.2%, 9.0%, 2.7% and 6.3% of the patients. The overall incidences of cardiovascular complications were 11.6%, including unstable angina (n=1, 0.9%), hypotention (n=1, 0.9%), congestive heart failure (n=2, 1.8%) and new-onset atrial fibrillation (n=10, 9.0%). There was no perioperative death. No major adverse cardiac events (MACE) occurred., Conclusions: It was safety to discontinued oral antiplatelet agents before operation, with no MACE and death in perioperative period.

To investigate the difference in messenger ribonucleic acid (mRNA) and protein expression of growth arrest DNA damage-inducible gene 45α (GADD45α), mouse double minute 2 homolog (MDM2), and P73 in cancer and cancer-adjacent tissues in patients with non-small-cell lung carcinoma (NSCLC).We compared the mRNA expression of GADD45α and MDM2 and the protein expression of GADD45α, MDM2, and P73 in lung cancer and cancer-adjacent tissues in NSCLC patients by quantitative real-time PCR, immunohistochemistry (IHC), and Western Blot (WB). We analyzed GADD45α, MDM2, and P73 expression in patients with different pathological types of NSCLC, and the correlation of these genes with gender, smoking history, and TNM/T stages.IHC results suggested that MDM2 protein expression significantly increased in cancer tissues in female patients (P = .01), but not in male patients. In addition, WB results indicated that P73 protein expression significantly decreased in cancer tissues in patients with adenocarcinoma (P = .03), but not squamous carcinoma.MDM2 and P73 protein levels were differentially regulated in cancer and cancer-adjacient tissues in patients with sub types of NSCLC. There was no significant difference in GADD45α expression between cancer and cancer-adjacent tissues in NSCLC patients.

The lateral habenula (LHb) is activated by a range of aversive states including those related to alcohol withdrawal and has glycine receptors (GlyRs), a sensitive target of alcohol. However, whether GlyRs in the LHb contribute to alcohol-related behaviors is unknown. Here, we report that rats experiencing withdrawal from chronic alcohol consumption showed higher anxiety and sensitivity to stress compared to their alcohol-naïve counterparts. Intra-LHb injection of glycine attenuated these aberrant behaviors and reduced alcohol intake upon alcohol re-access. Glycine's effect was blocked by strychnine, a GlyR antagonist, indicating that it was mediated by strychnine-sensitive GlyRs. Conversely, intra-LHb strychnine elicited anxiety- and depression-like behaviors in Naïve rats but not in withdrawal rats. Additionally, both the frequency and the amplitude of the spontaneous IPSCs were lower in LHb neurons in slices of withdrawal rats compared to naïve rats. Also, there were sporadic strychnine-sensitive synaptic events in some LHb neurons. Bath perfusion of strychnine induced a depolarizing inward current and increased action potential firings in LHb neurons. By contrast, bath perfusion of glycine or sarcosine, a glycine transporter subtype 1 inhibitor, inhibited LHb activity. Collectively, these data reveal that LHb neurons are under the tonic glycine inhibition both in physiological and pathological conditions. Activation of GlyRs reverses LHb hyperactivity, alleviates aberrant behaviors, and reduces alcohol intake, thus highlighting the GlyRs in the LHb as a potential therapeutic target for alcohol-use disorders., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The SDF-1/CXCR4 signaling plays a critical role in the trafficking of mesenchymal stem cells (MSCs) to the sites of tissue damage. Our recent study demonstrated that atorvastatin (ATV) treatment improved the survival of MSCs, and ATV pretreated MSCs ( ATV- MSCs) exhibited enhanced engraftment to injured myocardium. In this study, we investigated whether combined treatment with ATV and ATV- MSCs enhances cardiac repair and regeneration by activating SDF-1/CXCR4 signaling in a rat model of acute myocardial infarction. Rats were randomized into eight groups: the Sham, AMI control and 6 other groups that were subjected to AMI followed by treatment with MSCs, ATV, ATV+MSCs, ATV- MSCs, ATV+ ATV- MSCs, ATV+ ATV- MSCs+AMD3100 (SDF-1/CXCR4 antagonist), respectively. ATV+ ATV- MSCs significantly potentiated targeted recruitment of MSCs to peri-infarct myocardium and resulted in further improvements in cardiac function and reduction in scar size compared with MSCs treatment alone at 4-week after AMI. More importantly, the cardioprotective effects conferred by ATV+ ATV- MSCs were almost completely abolished by AMD3100 treatment. Together, our study demonstrated that ATV+ ATV- MSCs significantly enhanced the targeted recruitment and survival of transplanted MSCs, and resulted in subsequent cardiac function improvement by augmenting SDF-1/CXCR4 signaling., Competing Interests: None.

Objective: To evaluate the sterilization effect of new designed atmospheric low temperature plasma jet on Candida albicans ( C. albicans ) biofilm., Methods: C. albicans was grown into the logarithmic phase, and then was added to polystyrene 24-well microtitre plate. The amount of germs were calculated by viable plate counting to determine the reproducibility of each biofilm well. The germs in biofilm were treated by plasma for different exposure time and then the survived germs were quantified by plate counting, the dead cells were determined by staining the biofilm with propidium iodide (PI), and the ultrastructural changes of the germs in biofilm were observed by transmission electron microscopy (TEM)., Results: When incubated for 72 h, germs tightly polymerized and classical mature biofilm were formed. This atmospheric low temperature plasma jet could inactivate C. albicans biofilm within a short exposure time. C. albicans were 90% inactivated when treated 20 s and 55 s of plasma treatment reduced bacteria populations to undetectable levels. With the increase of treatment time, enlarged fluorescent positive area appeared, and more bacteria died with the extending of exposure. The TEM scanning results showed that the new plasma jet inactivated C. albicans biofilm mainly via disrupting cell envelopes and then leading the release of cellular components, thus resulting in loss of cell viability., Conclusion: Plasma generated from atmospheric low temperature plasma jet could damage the cell structure of C. albicans and efficiently sterilize C. albicans biofilm., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Science Edition).)

Objective: Endothelial barrier function in the onset and Tongxinluo (TXL) protection of myocardial ischemia/reperfusion (I/R) injury, and TXL can induce the secretion of Angiopoietin-like 4 (Angptl4) in human cardiac microvascular endothelial cells during hypoxia/reoxygenation. We intend to demonstrate whether TXL can attenuate myocardial I/R injury in diabetes, characterized with microvascular endothelial barrier disruption, by induction of Angptl4-mediated protection of endothelial barrier integrity., Methods and Results: I/R injury was created by coronary ligation in ZDF diabetic and non-diabetic control rats. The animals were anesthetized and randomized to sham operation or I/R injury with or without the exposure to insulin, rhAngptl4, TXL, Angptl4 siRNA, and the PPAR-α inhibitor MK886. Tongxinluo, insulin and rhAngptl4 have the similar protective effect on diabetic hearts against I/R injury. In I/R-injured diabetic hearts, TXL treatment remarkably reduced the infarct size, and protected endothelial barrier integrity demonstrated by decreased endothelial cells apoptosis, microvascular permeability, and myocardial hemorrhage, fortified tight junction, and upregulated expression of JAM-A, integrin-α5, and VE-cadherin, and these effects of TXL were as effective as insulin and rhAngptl4. However, Angptl4 knock-down with siRNA interference and inhibition of PPAR-α with MK886 partially diminished these beneficial effects of TXL and rhAngptl4. TXL induced the expression of Angptl4 in I/R-injured diabetic hearts, and was canceled by Angptl4 siRNA and MK886. TXL treatment increased myocardial PPAR-α activity, and was abolished by MK886 but not by Angptl4 siRNA., Conclusions: TXL protects diabetic hearts against I/R injury by activating Angptl4-mediated restoration of endothelial barrier integrity via the PPAR-α pathway., Competing Interests: The authors have declared that no competing interests exist.

Although initially effective against metastatic colorectal cancer (CRC), irinotecan-based chemotherapy leads to resistance and adverse toxicity. Curcumin is well known for its anti-cancer effects in many cancers, including CRC. Here, we describe reactive oxygen species (ROS) generation and endoplasmic reticulum (ER) stress as important mechanisms by which curcumin enhances irinotecan's effects on CRC cells. CRC cell lines were treated with curcumin and/or irinotecan for 24 h, and then evaluated using cell proliferation assays, cell apoptosis assays, cell cycle analysis, intracellular Ca2+ measurements, ROS measurements and immunoblotting for key ER stress-related proteins. We found that cell viability was inhibited and apoptosis was increased, accompanied by ROS generation and ER stress activation in CRC cells treated with curcumin alone or in combination with irinotecan. Blocking ROS production attenuated the expression of two markers of ER stress: binding of immunoglobulin protein (BIP) and CCAAT/enhancer-binding protein homologous protein (CHOP). Blocking CHOP expression using RNA interference also inhibited ROS generation. These results demonstrated that curcumin could enhance the effects of irinotecan on CRC cells by inhibiting cell viability and inducing cell cycle arrest and apoptosis, and that these effects may be mediated, in part, by ROS generation and activation of the ER stress pathway.

In current scenario, crop productivity is being challenged by decreasing soil fertility. To cope up with this problem, different beneficial microbes are explored to increase the crop productivity with value additions. In this study, Brassica napus L., an important agricultural economic oilseed crop with rich source of nutritive qualities, was interacted with Piriformospora indica, a unique root colonizing fungus with wide host range and multifunctional aspects. The fungus-treated plants showed a significant increase in agronomic parameters with plant biomass, lodging-resistance, early bolting and flowering, oil yield and quality. Nutritional analysis revealed that plants treated by P. indica had reduced erucic acid and glucosinolates contents, and increased the accumulation of N, Ca, Mg, P, K, S, B, Fe and Zn elements. Low erucic acid and glucosinolates contents are important parameters for high quality oil, because oils high in erucic acid and glucosinolates are considered undesirable for human nutrition. Furthermore, the expression profiles of two encoding enzyme genes, Bn-FAE1 and BnECR, which are responsible for regulating erucic acid biosynthesis, were down-regulated at mid- and late- life stages during seeds development in colonized plants. These results demonstrated that P. indica played an important role in enhancing plant growth, rapeseed yield and quality improvement of B. napus., (Copyright © 2017 Elsevier GmbH. All rights reserved.)

Objectives: To predict and analyze the antigenic epitopes in Mycobacterium tuberculosis protein caseinolytic protease P2 (clpP2), and explore its possibility to be applied as a new tuberculosis (TB) vaccine and drug development target., Methods: Secondary structure of clpP2 based on nucleic sequence was predicted by DNA Star software. The homologous sequence conformation were analyzed by Swiss-Model online software. T cells antigenic epitopes were predicted through VaxiPred, and B cell epitopes were predicted by combining use of several different prediction programs, such as ABCpred, COBEPro and BepiPredPred. The immune characteristics of clpP2 were analyzed by DNA Star, SignalP, TMHMM online software and were searched through NCBI database., Results: clpP2 protein was diverse in structure, composing with a great deal of CTL and Th cell epitopes. clpP2 was also predicted to comprise rich potential liner and discontinuous B-cell epitopes. These epitopes were accessible on the protein surface, located in flexible and hydrophilic regions., Conclusion: clpP2 is prompted to induce immune responses and developes a novel target in surveillance, treatment and vaccine.

A safe and effective Hantaan virus (HTNV) vaccine is highly desirable because HTNV causes an acute and often fatal disease (hemorrhagic fever with renal syndrome, HFRS). Since the immunity of the inactivated vaccine is weak and the safety is poor, HTNV virus-like particles (VLPs) offer an attractive and safe alternative. These particles lack the viral genome but are perceived by the immune system as virus particles. We hypothesized that adding immunostimulatory signals to VLPs would enhance their efficacy. To accomplish this enhancement, we generated chimeric HTNV VLPs containing glycosylphosphatidylinositol (GPI)-anchored granulocyte macrophage colony-stimulating factor (GM-CSF) or CD40 ligand (CD40L) and investigated their biological activity in vitro . The immunization of mice with chimeric HTNV VLPs containing GM-CSF or CD40L induced stronger humoral immune responses and cellular immune responses compared to the HTNV VLPs and Chinese commercial inactivated hantavirus vaccine. Chimeric HTNV VLPs containing GM-CSF or CD40L also protected mice from an HTNV challenge. Altogether, our results suggest that anchoring immunostimulatory molecules into HTNV VLPs can be a potential approach for the control and prevention of HFRS.

The cytotoxic T lymphocyte (CTL) response plays a key role in controlling viral infection, but only a few epitopes within the HTNV glycoprotein (GP) that are recognized by CTLs have been reported. In this study, we identified one murine HTNV GP-derived H2-K b -restricted CTL epitope in C57BL/6 mice, which could be used to design preclinical studies of vaccines for HTNV infection. First, 15 8-mer peptides were selected from the HTNV GP amino acid sequence based on a percentile rank of <=1% by IEDB which is the most comprehensive collection of epitope prediction and analysis tool. A lower percentile rank indicates higher affinity and higher immune response. In the case of the consensus method, we also evaluated the binding score of peptide-binding affinity by the BIMAS software to confirm that all peptides were able to bind H2-K b . Second, one novel GP-derived CTL epitope, GP6 aa456-aa463 (ITSLFSLL), was identified in the splenocytes of HTNV-infected mice using the IFN-γ ELISPOT assay. Third, a single peptide vaccine was administered to C57BL/6 mice to evaluate the immunogenic potential of the identified peptides. ELISPOT and cell-mediated cytotoxicity assays showed that this peptide vaccine induced a strong IFN-γ response and potent cytotoxicity in immunized mice. Last, we demonstrated that the peptide-vaccinated mice had partial protection from challenge with HTNV. In conclusion, we identified an H2-K b -restricted CTL epitope with involvement in the host immune response to HTNV infection.

Inhibitor of differentiation 4 (Id4) plays an important role in tumorigenesis, but its role in cancer chemoresistance remains unclear. Our study showed that Id4 expression in cisplatin-resistant A549/DDP cells was higher than that in parental A549 cells. Moreover, overexpression of Id4 in A549 cells results in cisplatin resistance and apoptosis inhibition, while increasing the IC50 for cisplatin through activation of phospho-p38 MAPK. However, Id4 knockdown in A549/DDP cells was shown to resensitize A549/DDP cells to cisplatin and induce apoptosis, as well as decrease the IC50 for cisplatin through inactivation of phospho-p38 MAPK. In addition, a p38 MAPK inhibitor (SB202190) could partly reverse both Id4-reduced apoptosis and Id4-induced cisplatin resistance. These results suggest that Id4 inhibits cisplatin-induced apoptosis in human lung adenocarcinoma, partially through activation of the p38 MAPK pathway. Our research indicates that Id4 may be a new target for non-small-cell lung cancer treatment.

Objectives: Genetic construction of tuberculosis vaccine candidates based on Listeria(L.) monocytogenes,L.ivanovii ,and evaluation their protein expression,in order to provide a novel method for research on tuberculosis controlling., Methods: Two kinds of gene cassettes carrying tuberculosis antigen encoding gene Rv3875 or Rv0129c were inserted into targeting vector harboring L.monocytogenes,L.ivanovii homologous sequences via genetic connection methods and plasmid transformation technology in vitro .Targeting plasmids were electroporated into L.monocytogenes,L.ivanovii ,and the recombinant strains were experienced serial passage at 42 °C and 30 °C.Subsequently,the tuberculosis antigen gene cassettes in targeting plasmids were integrated into L.monocytogenes and L.ivanovii attenuated strain (knocking out of virulence gene actA and plcB ) and L.ivanovii wild type strain by homologous recombination and gene targeting technology.The recombinant strains were screened by blue-white spot and antibiotic resistance test;the intracellular and extracellular proteins of the recombinant strains were tested by Western blot., Results: Five recombination strains carried antigen gene cassette were constructed,and the recombinant genome were confirmed by PCR and sequencing.No erythromycin resistance gene was found in 5 strains,which was coincident to expection.Recombination strains Li-Rv0129c,Li-ΔactAplcB-Rv0129c and Li-ΔactAplcB-Rv3875 expressed Mycobacterium tuberculosis antigenic protein,Ag85C or ESAT-6,as expected.But L.monocytogenes strains did not express proper antigenic protein., Conclusions: Three novel L.ivanovii -based tuberculosis vaccine candicates,carrying Mycobacterium tuberculosis Rv0129c antigen gene cassette (coding for Ag85C) or Rv3875 gene cassette (coding for ESAT-6),and expressing relevant antigenic proteins have been successfully selected.

Cardiac microvascular endothelial cells (CMECs) extensively secrete cytokines during myocardial ischemia/reperfusion injury (MIRI). Tongxinluo (TXL) has been demonstrated to preserve the function of the endothelium and myocardium against MIRI. This study was designed to identify alterations in the paracrine function of CMECs under hypoxia/reoxygenation (H/R) conditions and assess its modulation by TXL. CMECs were exposed to different concentrations of TXL for 30 min and then subjected to hypoxia and reoxygenation for 12 and 2 h, respectively. Apoptosis was measured to determine the optimal TXL concentration. Protein antibody arrays were used to assess changes in cytokines secreted into conditioned medium by CMECs. A Gene Ontology (GO) analysis was applied to interpret the functional implications of changes in cytokines. TXL inhibited CMEC apoptosis in a concentration-dependent manner after H/R, reaching peak efficacy at a concentration of 800 μg/ml. H/R significantly altered 33 cytokines, and TXL (800 μg/ml) changed the levels of 121 different cytokines compared with the H/R group. Among these cytokines, 10 that were increased by H/R were decreased by TXL, five that were decreased by H/R were increased by TXL, and eight that were attenuated by H/R were further decreased by TXL. Insulin-like growth factor binding protein-1 was up-regulated by H/R and was further increased by TXL. Significantly altered factors were found to be involved in cell proliferation, growth and differentiation, as well as chemotaxis and transport. TXL inhibited the apoptosis of CMECs and modulated their paracrine function in MIRI.

Background: Video-assisted thoracoscopic surgery (VATS) thymectomy has become a feasible treatment for myasthenia gravis (MG) in recent years. The objective of the present meta-analysis was to evaluate the perioperative characteristics, safety, and completely stable remission rate in patients with MG who received VATS or open thymectomy (OT)., Methods: We searched PubMed, Embase, ScienceDirect, Web of Science, and CNKI for related articles using combinations of the search terms video-assisted thoracoscopic thymectomy, transsternal thymectomy, and MG. The inter-study heterogeneity was assessed by χ 2 -based Q statistics, and the extent of inconsistency was generated by I 2 statistics., Results: A total of 12 studies with 1173 patients were included, and there was no difference in the operation time (p = 0.08) and ICU time (p = 0.14) between the two groups, but VATS thymectomy was associated with less intra-operation blood loss and hospital time (p < 0.00001). VATS was also associated with lower rates of total complication (OR =0.59; 95% CI, 0.37-0.94; p = 0.03) and myasthenic crisis (OR = 0.51; 95% CI, 0.28-0.92; p = 0.03), but the rates of pneumonia (OR = 0.59; 95% CI, 0.29-1.32; p = 0.21) and complete remission rate (CSR) (OR = 0.64; 95% CI, 0.38-1.09; p = 0.10) had no obvious differences between the VATS and OT groups., Conclusion: Patients with MG undergoing VATS thymectomy achieved better surgical outcomes and fewer complications than those who received OT.

Background: Cisplatin-based chemotherapy is the standard first-line treatment for non-small-cell lung cancers (NSCLCs); however, the long-term therapeutic effect is reduced by chemoresistance. Brain and reproductive organ-expressed (BRE) proteins are overexpressed in several cancers and have an anti-apoptotic function. However, their biological role in the development of the chemoresistant phenotype of human NSCLC remains unknown. We investigate the differential expression of the BRE gene in human lung adenocarcinoma cell lines A549 and the cisplatin-resistant variant A549/cisplatin (DDP), and the mechanisms of cisplatin-resistance induced by the BRE gene., Methods: Cell counting kit-8 assay was employed to determine the sensitivity of A549 and A549/DDP cell lines to cisplatin. BRE expression was measured using quantitative real time-polymerase chain reaction and western blot analysis. The apoptosis rate of lung adenocarcinoma cells was determined by flow cytometry., Results: BRE expression in A549 cells, derived from human lung cells, was markedly decreased compared with parental cisplatin-resistant A549/DDP cells at messenger ribonucleic acid and protein levels. BRE overexpression in A549 significantly decreased sensitivity to DDP by inhibiting cell apoptosis. Conversely, BRE knockdown in A549/DDP cells increased their chemosensitivity. Importantly, we demonstrate that BRE overexpression induces the expression of phosphoprotein kinase B (p-Akt) in lung cancer cells, while BRE silencing inhibits p-Akt expression. Furthermore, downregulation of p-Akt by LY294002 reversed the DDP resistance induced by BRE by increasing apoptosis. BRE enhances the DDP resistance of lung cancer cells through the Akt signaling pathway., Conclusion: Our findings provide new insight into the mechanism of DDP resistance in NSCLC cells and suggest BRE as an attractive new target for NSCLC treatment.

Background/aims: Poor viability of transplanted mesenchymal stem cells (MSCs) within the ischemic heart limits their therapeutic potential for cardiac repair. Globular adiponectin (gAPN) exerts anti-apoptotic effects on several types of stem cells. Herein, we investigated the effect of gAPN on the MSCs against apoptosis induced by hypoxia and serum deprivation (H/SD)., Methods: MSCs exposed to H/SD conditions were treated with different concentrations of gAPN. To identify the main type of receptor, MSCs were transfected with siRNA targeting adiponectin receptor 1 or 2 (AdipoR1 or AdipoR2). To elucidate the downstream pathway, MSCs were pre-incubated with AMPK inhibitor Compound C. Apoptosis, caspase-3 activity and mitochondrial membrane potential were evaluated., Results: H/SD-induced MSCs apoptosis and caspase-3 activation were attenuated by gAPN in a concentration-dependent manner. gAPN increased Bcl-2 and decreased Bax expressions. The loss of mitochondrial membrane potential induced by H/SD was also abolished by gAPN. The protective effect of gAPN was significantly attenuated after the knockdown of AdipoR1 rather than AdipoR2. Moreover, Compound C partly suppressed the anti-apoptotic effect of gAPN., Conclusions: gAPN inhibits H/SD-induced apoptosis in MSCs via AdipoR1-mediated pathway, possibly linked to the activation of AMPK. gAPN may be a novel survival factor for MSCs in the ischemic engraftment environment., (© 2016 The Author(s) Published by S. Karger AG, Basel.)

Background: Chinese bayberry (Myrica rubra Sieb. & Zucc.) is an important subtropical evergreen fruit tree in southern China. Generally dioecious, the female plants are cultivated for fruit and have been studied extensively, but male plants have received very little attention. Knowledge of males may have a major impact on conservation and genetic improvement as well as on breeding. Using 84 polymorphic SSRs, we genotyped 213 M. rubra individuals (99 male individuals, 113 female varieties and 1 monoecious) and compared the difference in genetic diversity between the female and the male populations., Results: Neighbour-joining cluster analysis separated M. rubra from three related species, and the male from female populations within M. rubra. By structure analysis, 178 M. rubra accessions were assigned to two subpopulations: Male dominated (98) and Female dominated (80). The well-known cultivars 'Biqi' and 'Dongkui', and the landraces 'Fenhong' are derived from three different gene pools. Female population had a slightly higher values of genetic diversity parameters (such as number of alleles and heterozygosity) than the male population, but not significantly different. The SSR loci ZJU062 and ZJU130 showed an empirical Fst value of 0.455 and 0.333, respectively, which are significantly above the 95 % confidence level, indicating that they are outlier loci related to sex separation., Conclusion: The male and female populations of Chinese bayberry have similar genetic diversity in terms of average number of alleles and level of heterozygosity, but were clearly separated by genetic structure analysis due to two markers associated with sex type, ZJU062 and ZJU130. Zhejiang Province China could be the centre of diversity of M. rubra in China, with wide genetic diversity coverage; and the two representative cultivars 'Biqi' and 'Dongkui', and one landrace 'Fenhong' in three female subpopulations. This research provides genetic information on male and female Chinese bayberry and will act as a reference for breeding programs.

Objective: Tongxinluo (TXL) has been shown to decrease myocardial necrosis after ischemia/reperfusion (I/R) by simulating ischemia preconditioning (IPC). However, the core mechanism of TXL remains unclear. This study was designed to investigate the key targets of TXL against I/R injury (IRI) among the cardiac structure-function network., Materials and Methods: To evaluate the severity of lethal IRI, a mathematical model was established according to the relationship between myocardial no-reflow size and necrosis size. A total of 168 mini-swine were employed in myocardial I/R experiment. IRI severity among different interventions was compared and IPC and CCB groups were identified as the mildest and severest groups, respectively. Principal component analysis was applied to further determine 9 key targets of IPC in cardioprotection. Then, the key targets of TXL in cardioprotection were confirmed., Results: Necrosis size and no-reflow size fit well with the Sigmoid Emax model. Necrosis reduction space (NRS) positively correlates with I/R injury severity and necrosis size (R2=0.92, R2=0.57, P<0.01, respectively). Functional and structural indices correlate positively with NRS (R2=0.64, R2=0.62, P<0.01, respectively). TXL recovers SUR2, iNOS activity, eNOS activity, VE-cadherin, β-catenin, γ-catenin and P-selectin with a trend toward the sham group. Moreover, TXL increases PKA activity and eNOS expression with a trend away from the sham group. Among the above nine indices, eNOS activity, eNOS, VE-cadherin, β-catenin and γ-catenin expression were significantly up-regulated by TXL compared with IPC (P>0.05) or CCB (P<0.05) and these five microvascular barrier-related indices may be the key targets of TXL in minimizing IRI., Conclusions: Our study underlines the lethal IRI as one of the causes of myocardial necrosis. Pretreatment with TXL ameliorates myocardial IRI through promoting cardiac microvascular endothelial barrier function by simulating IPC.