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For a long time, seasonal drought occurs frequently in Southwest China, and the management of water and fertilizer in kiwifruit orchards has no quantitative standards, which seriously affects the yield and quality of kiwifruit. Therefore, the effects of water and fertilizer deficit regulation with drip irrigation (WFDRDI) on the quality of kiwifruit at different growth stages were explored to achieve water and fertilizer saving, and green and efficient production of kiwifruit. We select ‘Jin Yan’ kiwifruit and set two water deficit levels (WD20% and WD40%) and three fertilizer deficit levels (FD15%, FD30% and FD45%) at bud burst to leafing stage (stage I), flowering to fruit set stage (stage II), fruit expansion stage (stage III) and fruit maturation stage (stage IV), respectively, with a full irrigation and fertilization as the control treatment (CK) in 2017 and 2018. Results showed that the WFDRDI at stage II and III had significant effect on fruit physical quality of kiwifruit, specifically, the III-WD40%FD30% and III-WD20%FD45% treatments significantly increased fruit firmness by 13.62 and 15.59% (P

BackgroundInitial choices of antimicrobial therapy for most cases of community-acquired pneumonia (CAP) in children under 5 years of age are typically based on local epidemiology, risk factors assessment, and subsequent clinical parameters and positive cultures, which can lead to the underdiagnosis and underestimation of lung infections caused by uncommon pathogens. Contezolid, an orally administered oxazolidinone antibiotic, gained approval from the National Medical Products Administration (NMPA) of China in June 2021 for managing complicated skin and soft tissue infections (cSSTI) caused by staphylococcus aureus (SA), streptococcus pyogenes, or streptococcus agalactis. Owing to its enhanced safety profile and ongoing clinical progress, the scope of contezolid's clinical application continues to expand, benefiting a growing number of patients with Gram-positive bacterial infections.Case summaryIn this report, we present the first use of contezolid in a toddler with severe CAP caused by SA, aiming to avoid potential adverse drug reactions (ADRs) associated with vancomycin and linezolid.ConclusionAlthough contezolid has not been officially indicated for CAP, it has been shown to be effective and safe in the management of SA-induced severe CAP in this toddler, suggesting its potential as an alternative option in the dilemma, especially for patients who are susceptible or intolerant to ADRs associated with first-line anti-methicillin-resistant staphylococcus aureus (MRSA) antimicrobial agents.

Rocky desertification is a devastating process in Karst areas of Southwest China and induces serious fragmentation in ecosystems. Therefore, vegetation restoration and the scientific evaluation of soil quality are key restorative strategies in these areas. In this study, a natural closed forest and a disturbed forest with three restoration models, including an evergreen broad-leaved forest, mixed forest, and deciduous forest, were investigated in Huanjiang County. More than nineteen soil properties (including physical, chemical, and biotic properties) were analyzed across treatments, and principal component analyses (PCA) were combined with a minimum data set (MDS) applied to evaluate the soil quality. Our study sought to identify a vegetation restoration model to improve the soil quality in this area. We demonstrated that soil physical and chemical properties, microbial biomass, and enzyme activities significantly differed across all of the models. Soil water content, capillary porosity, total porosity, organic carbon, total phosphorus, available phosphorus, and urease activity were high in the mixed forest, leading to better physical soil properties. Also, relatively high soil total nitrogen, total potassium, available nitrogen, available potassium, microbial biomass C and N, catalase, sucrose, and alkaline phosphatase levels were observed in the deciduous broad-leaved forest, resulting in improved soil chemical properties. Based on the minimum data set (MDS) method, six indicators, including non-capillary porosity, organic carbon, total phosphorus, pH, microbial biomass nitrogen, and urease activity, were selected to evaluate the soil quality across the models. Our data showed that, among the five models, the deciduous broad-leaved forest had the highest soil quality index (0.618), followed by the mixed forest (0.593). Stepwise regression analysis showed that soil organic carbon explained 79.9% of the variations in the soil quality indices, suggesting it was a major factor affecting the soil quality. Thus, vegetation restoration models mainly comprised of native tree species effectively improved the soil quality in Karst rocky desertification areas, with deciduous broad-leaved forests displaying the best effects, followed by mixed forests.

Background. Acute liver failure (ALF), previously known as fulminant hepatic failure, has become a common, rapidly progressive, and life-threatening catastrophic hepatic disease in intensive care unit (ICU) due to the continuous increase in drug abuse, viral infection, metabolic insult, and auto-immune cause. At present, plasma exchange (PE) is the main effective alternative treatment for ALF in ICU clinical practice, and high-volume plasma exchange (HVP) has been listed as a grade I recommendation for ALF management in the American Society for Apheresis (ASFA) guidelines. However, no existing models can provide a satisfactory performance for clinical prediction on 90-day transplant-free mortality in adult patients with ALF undergoing PE. Our study aims to identify a novel and simple clinical predictor of 90-day transplant-free mortality in adult patients with ALF undergoing PE. Methods. This retrospective study contained adult patients with ALF undergoing PE from the Medical ICU (MICU) in the Second Affiliated Hospital of Harbin Medical University between January 2017 and December 2020. Baseline and clinical data were collected and calculated on admission to ICU before PE, including gender, age, height, weight, body mass index (BMI), etiology, total bilirubin, direct bilirubin, indirect bilirubin, prothrombin activity, model for end-stage liver disease (MELD) score, and sequential organ failure assessment (SOFA) score. Enrolled adult patients with ALF undergoing PE were divided into a survival group and a death group at discharge and 90 days on account of medical records and telephone follow-up. After each PE, decreased rates of total bilirubin and MELD score and increased rates of prothrombin activity were calculated according to the clinical parameters. In clinical practice, different patients underwent different times of PE, and thus, mean decrease rates of total bilirubin and MELD score and mean increase rate of prothrombin activity were obtained for further statistical analysis. Results. A total of 73 adult patients with ALF undergoing 204 PE were included in our retrospective study, and their transplant-free mortality at discharge and 90 days was 6.85% (5/73) and 31.51% (23/73), respectively. All deaths could be attributed to ALF-induced severe and life-threatening complications or even multiple organ dysfunction syndrome (MODS). Most of the enrolled adult patients with ALF were men (76.71%, 56/73), with a median age of 48.77 years. Various hepatitis virus infections, unknown etiology, auto-immune liver disease, drug-induced liver injury, and acute pancreatitis (AP) accounted for 75.34%, 12.33%, 6.85%, 4.11%, and 1.37% of the etiologies in adult patients with ALF, respectively. Univariate analysis showed a significant difference in age, mean decrease rates of total bilirubin and MELD score mean increase rate of prothrombin activity, decrease rates of total bilirubin and MELD score, and increase rate of prothrombin activity after the first PE between the death group and survival group. Multivariate analysis showed that age and mean decrease rates of total bilirubin and MELD score were closely associated with 90-day transplant-free mortality in adult patients with ALF undergoing PE. The 90-day transplant-free mortality was 1.081, 0.908, and 0.893 times of the original value with each one-unit increase in age and mean decrease rates of total bilirubin and MELD score, respectively. The areas under the receiver operatingcharacteristic (ROC) curve of age, mean decrease rates of total bilirubin and MELD score, and the three combined were 0.689, 0.225, 0.123, and 0.912, respectively. The cut-off values of age, mean decrease rates of total bilirubin and MELD score, and the three combined were 61.50, 3.12, 1.21, and 0.33, respectively. The specificity and sensitivity of combined age with mean decrease rates of total bilirubin and MELD score for predicting 90-day transplant-free mortality in adult patients with ALF undergoing PE were 87% and 14%. Conclusion. Combined age with mean decrease rates of total bilirubin and MELD score as a novel and simple clinical predictor can accurately predict 90-day transplant-free mortality in adult patients with ALF undergoing PE, which is worthy of application and promotion in clinical practice, especially in the identification of potential transplant candidates.

This paper has aimed to review the available evidence on the association between Interleukin (IL) -10 -1082G/A, -592C/A gene polymorphisms and the risk of human immunodeficiency virus-1(HIV-1) infection. The data of PubMed updated in May 2021 were retrieved. The HIV infection risks were estimated in allelic, recessive, dominant, homozygous, heterozygous, over-dominant models of IL-10-1082G/A and-592C/A gene locus as odds ratio (OR) with the corresponding 95% confidence interval (95% CI). The correlation was not significant between -1082G/A polymorphism and HIV-1 susceptibility (allelic model (G vs. A: OR (95% CI)=0.968 (0.878-1.067)); recessive model (GG vs. AA+AG: OR (95% CI)=0.940, (0.771-1.146)); dominant model (GG+AG vs. AA: OR (95% CI)=0.967(0.846-1.106)); homozygous model (GG vs. AA: OR (95% CI)=0.971(0.780-1.209)); heterozygous model (AG vs. AA: OR (95% CI)=0.988(0.797-1.224)) and over-dominant model (GG+AA vs. AG: OR (95% CI)=0.969(0.781-1.201)). IL-10-592C/A polymorphism might be related to HIV-1 in allelic model, dominant model, homozygous model and heterozygous model (OR (95% CI)(0.796-0.965); OR (95% CI)=0.793(0.664-0.948); OR (95% CI)=0.755,(0.612-0.930); OR (95% CI)=0.820(0.679-0.991), respectively), but not to recessive model and over-dominant model (OR (95% CI)=0.882(0.770-1.010) and OR (95% CI)=1.009(0.897-1.148)).

AIM: To investigate the current quality of life in children with amblyopia and its influencing factors.METHODS: Cross-sectional study. Using random sampling method, 178 children with amblyopia were selected as the research objects, and the Chinese version of the Universal Core Scale of Children's Quality of Life was used to investigate the research objects. The impact of amblyopia on children's quality of life was analyzed. RESULTS:The quality of life score of children with amblyopia was(77.23±15.52)points. The results of multiple linear regression showed that parental education, left eye best-corrected visual acuity, right eye corrected visual acuity, coverage, premature delivery, hypoxia at birth and delivery way were the main factors affecting the quality of life of amblyopic children. It can explain 38.6% of the variance in the quality of life of children with amblyopia(F=15.242, P

Abstract. Background:. Drug-coated balloons (DCBs) have emerged as potential alternatives to drug-eluting stents in specific lesion subsets for de novo coronary lesions. Quantitative flow ratio (QFR) is a method based on the three-dimensional quantitative coronary angiography and contrast flow velocity during coronary angiography (CAG), obviating the need for an invasive fractional flow reserve procedural. This study aimed to assess the serial angiographic changes of de novo lesions post-DCB therapy and further explore the cut-off values of lesion and vessel QFR, which predict vessel restenosis (diameter stenosis [DS] ≥50%) at mid-term follow-up. Methods:. The data of patients who underwent DCB therapy between January 2014 and December 2019 from the multicenter hospital were retrospectively collected for QFR analysis. From their QFR performances, which were analyzed by CAG images at follow-up, we divided them into two groups: group A, showing target vessel DS ≥50%, and group B, showing target vessel DS

Abstract We study the CP violation in two-body nonleptonic decays of $$B_c$$ B c meson. We concentrate on the decay channels which contain at least one excited heavy meson in the final states. Specifically, the following channels are considered: $$B_c\rightarrow c{\bar{c}}(2S, 2P)+{\bar{c}}q(1S, 1P)$$ B c → c c ¯ ( 2 S , 2 P ) + c ¯ q ( 1 S , 1 P ) , $$B_c\rightarrow c{\bar{c}}(1S)+{\bar{c}}q(2S, 2P)$$ B c → c c ¯ ( 1 S ) + c ¯ q ( 2 S , 2 P ) , $$B_c\rightarrow c{\bar{c}}(1P)+{\bar{c}}q(2S)$$ B c → c c ¯ ( 1 P ) + c ¯ q ( 2 S ) , $$B_c\rightarrow c{\bar{c}}(1D)+{\bar{c}}q(1S, 1P)$$ B c → c c ¯ ( 1 D ) + c ¯ q ( 1 S , 1 P ) , and $$B_c\rightarrow c{\bar{c}}(3S)+{\bar{c}}q(1S)$$ B c → c c ¯ ( 3 S ) + c ¯ q ( 1 S ) . The improved Bethe-Salpeter method is applied to calculate the hadronic transition matrix element. Our results show that some decay modes have large branching ratios, which is of the order of $$10^{-3}$$ 10 - 3 . The CP violation effect in $$B_c \rightarrow \eta _c(1S)+D(2S)$$ B c → η c ( 1 S ) + D ( 2 S ) , $$B_c \rightarrow \eta _c(1S)+D_0^{*}(2P)$$ B c → η c ( 1 S ) + D 0 ∗ ( 2 P ) , and $$B_c \rightarrow J/\psi +D^{*}(2S)$$ B c → J / ψ + D ∗ ( 2 S ) are most likely to be found. If the detection precision of the CP asymmetry in such channels can reach the $$3\sigma $$ 3 σ level, at least $$10^7$$ 10 7 $$B_c$$ B c events are needed.

Oxide metallurgy technology can improve the microstructure of a coarse-grained heat-affected zone (CGHAZ) but introduces extra inclusions. Local corrosion behavior of the CGHAZ of a Zr–Ti–Al–RE deoxidized steel was investigated in this work using theoretical calculations and experimental verification. The modified inclusions have a (Zr–Mg–Al–Ca–RE)Ox core claded by a CaS and TiN shell. CaS dissolves first, followed by the oxide core, leaving TiN parts. This confirms that the addition of rare earth can reduce lattice distortion and prevent a galvanic couple between the inclusions and the matrix, while the chemical dissolution of CaS causes localized acidification, resulting in the pitting corrosion initiation.

Abstract Considering Z(3930) and X(4160) as $$\chi _{c2}(2P)$$ χc2(2P) and $$\chi _{c2}(3P)$$ χc2(3P) states, the semileptonic and nonleptonic of $$B_c$$ Bc decays to Z(3930) and X(4160) are studied by the improved Bethe–Salpeter (B–S) Method. The form factors of decay are calculated through the overlap integrals of the meson wave functions in the whole accessible kinematical range. The influence of relativistic corrections are considered in the exclusive decays. Branching ratios of $$B_c$$ Bc weak decays to Z(3930) and X(4160) are predicted. Some of the branching ratios are: $$Br(B_c^+\rightarrow Z(3930)e^+\nu _e)=(3.03^{+0.09}_{-0.16})\times 10^{-4}$$ Br(Bc+→Z(3930)e+νe)=(3.03-0.16+0.09)×10-4 and $$Br(B_c^+\rightarrow X(4160)e^+\nu _e)=(3.55^{+0.83}_{-0.35})\times 10^{-6}$$ Br(Bc+→X(4160)e+νe)=(3.55-0.35+0.83)×10-6 . These results may provide useful information to discover Z(3930) and X(4160) and the necessary information for the phenomenological study of $$B_c$$ Bc physics.

The first-line treatment options for high-risk prostate cancer (PCa) are definitive external beam radiotherapy (EBRT) with or without androgen deprivation therapy (ADT) and radical prostatectomy (RP) with or without adjuvant therapies. However, few randomized trials have compared the survival outcomes of these two treatments. To systematically evaluate the survival outcomes of high-risk PCa patients treated with EBRT- or RP-based therapy, a comprehensive and up-to-date meta-analysis was performed. A systematic online search was conducted for randomized or observational studies that investigated biochemical relapse-free survival (bRFS), cancer-specific survival (CSS), and/or overall survival (OS), in relation to the use of RP or EBRT in patients with high-risk PCa. The summary hazard ratios (HRs) were estimated under the random effects models. We identified heterogeneity between studies using Q tests and measured it using I2 statistics. We evaluated publication bias using funnel plots and Egger's regression asymmetry tests. Seventeen studies (including one randomized controlled trial [RCT]) of low risk of bias were selected and up to 9504 patients were pooled. When comparing EBRT-based treatment with RP-based treatment, the pooled HRs for bRFS, CSS, and OS were 0.40 (95% confidence interval [CI]: 0.24–0.67), 1.36 (95% CI: 0.94–1.97), and 1.39 (95% CI: 1.18–1.62), respectively. Better OS for RP-based treatment and better bRFS for EBRT-based treatment have been identified, and there was no significant difference in CSS between the two treatments. RP-based treatment is recommended for high-risk PCa patients who value long-term survival, and EBRT-based treatment might be a promising alternative for elderly patients.

The dynamic interaction between the ground fissure and an oblique two-section horseshoe-shaped subway tunnel under the subway dynamic load was investigated based on a series of model tests in this study. The results indicated that the subway subway-induced vibration attenuated in different degrees when propagating in the directions in the soil layer, while the ground fissure had an attenuation effect on subway vibration. Furthermore, the vibration of the soil layer below the tunnel near the ground fissure was stronger than that of the upper soil layer, and the vibration response at the tunnel bottom was stronger than that of the arch waist and the tunnel crown. The additional contact pressure between the tunnel bottom and the soil was relatively large when the ground fissure was not active, while the additional strain at the top and bottom of the tunnel caused by the excitation was small. Moreover, when the hanging wall of the ground fissure descended, the additional contact pressure at the tunnel crown in the hanging wall and the tunnel bottom in the footwall significantly increased, and a negative additional stain was identified at those two positions. Meanwhile, a positive additional stain was identified at the tunnel crown in the footwall and the tunnel crown in the hanging wall, increasing with the descent of the hanging wall.

BackgroundBladder cancer is the 10th most common cancer and most common urothelial malignancy worldwide. Prognostic biomarkers for bladder cancer patients are required for individualized treatment. Monocarboxylate transporter 4 (MCT4), encoded by SLC16A3 gene, is a potential biomarker for bladder cancer because of its crucial role in the lactate efflux in the aerobic glycolysis process. We aimed to study the association between MCT4 expression and the overall survival (OS) of bladder cancer patients.MethodsThe published single-cell RNA sequencing data of 49,869 bladder cancer cells and 15,827 normal bladder mucosa cells and The Cancer Genome Atlas (TCGA) bladder cancer cohort data were used to explore the mRNA expression of SLC16A3 in bladder cancer. Eighty-nine consecutive bladder cancer patients who had undergone radical cystectomy were enrolled as a validation cohort. The expression of MCT4 proteins in bladder cancer specimens was detected using immunohistochemistry staining. The Kaplan–Meier survival analysis and Cox regression were performed to analyze the association between MCT4 protein expression and OS in bladder cancer patients.ResultsSLC16A3 mRNA was upregulated in bladder cancer cells. The upregulated genes in SLC16A3-positive epithelial cells were enriched in the glycolysis process pathway and monocarboxylic acid metabolic process pathway. Patients with high SLC16A3 mRNA expression showed significantly poor OS (p = 0.016). High MCT4 protein expression was also found to be an independent predictor for poor OS in bladder cancer patients (HR: 2.462; 95% CI: 1.202~5.042, p = 0.014). A nomogram was built based on the results of the multivariate Cox analysis.ConclusionBladder cancer with high SLC16A3 mRNA expression has a poor OS. High MCT4 protein expression is an independent prognostic factor for bladder cancer patients who had undergone radical cystectomy.

The platinum-based, two-drug, 3-week regimen is currently the main first-line chemotherapy program for the treatment of advanced squamous cell lung cancer. The aim of this phase II clinical study was to evaluate the efficacy and adverse events of the bi-weekly program of liposomal paclitaxel combined with nedaplatin as a first-line treatment for advanced squamous cell lung cancer. A total of 52 cases of advanced squamous cell lung cancer were included in this phase II clinical trial. Patients received intravenous infusion of liposomal paclitaxel (100 mg/m2) and nedaplatin (50 mg/m2) on days 1 and 15 of a 4-week cycle. Each patient received two to six cycles of chemotherapy, consistent with the regimen of combined liposomal paclitaxel and nedaplatin. The total effective rate of this chemotherapy program was 37.5%. The median progression-free survival time was 8.5 months (95% confidence interval: 7.8–9.2). The median survival time was 16 months (95% confidence interval: 14.1–17.9). The main adverse event was myelosuppression. Grade 3 leukopenia was noted in seven patients (13.5%), and no grade 4 leukopenia was observed. Grade 3 anemia was noted in four patients (7.7%), and no grade 4 anemia was observed. In addition, no grade 2 or higher thrombocytopenia and no grade 3 or 4 non-bone marrow toxicity was detected. The bi-weekly program of liposomal paclitaxel combined with nedaplatin is effective for the treatment of advanced squamous cell lung cancer, with high safety and few adverse events. However, additional studies are warranted to confirm these results. The trial was registered under the number ChiCTR-OIN-17011423.

Background According to the current clinical guidelines, chemoradiotherapy is considered the standard treatment for locally advanced non‐small cell lung cancer (NSCLC). We analyzed the prognostic effect of adjuvant chemotherapy (ACT) in resected patients using the new eighth tumor node metastasis (TNM) staging systems based on the Surveillance, Epidemiology and End Results database. Methods We identified 3008 patients with stage IIIA NSCLC (T4N0M0) who underwent sublobar resection, lobectomy, or pneumonectomy. Covariates affecting treatment selection or survival were included as part of propensity score models for matching and weighting. The effect of ACT on survival was assessed, stratified by postoperative radiation therapy (PORT) use, tumor size, and age. Results Analyses of 2016 patients were conducted with standardized differences in covariates < 10% after matching. ACT was associated with significantly improved five‐year overall survival (51.1% vs. 39.7%; P = 0.0260) in patients aged 21–65 with > 7 cm tumors, even after adjusting for the presence or absence of the superior sulcus (P = 0.0003). No significant outcomes were observed using other stratifications in the matched analysis. Moreover, ACT with PORT conferred a potential survival benefit in 21–65‐year‐old patients with 0–7 cm tumors (for all causes of death: hazard ratio 0.414, 95% confidence interval 0.251–0.684). Conclusion In this population‐based cohort, ACT prolonged the survival of patients aged 21–65 with a tumor > 7 cm, with or without PORT. Inverse probability of treatment weighting can estimate the treatment effect and is suitable for use with survival data.

Real-world images usually contain multiple objects, as a result, generating an image from a multi-instance sketch is an attractive research topic. However, existing generative networks usually produce a similar texture on different instances for those methods focus on learning the distribution of the whole image. To address this problem, we propose a progressive instance texture reserved generative approach to generate more convincible images by decoupling the generation of the instances and the whole image. Specifically, we create an instance generator to synthesize the primitive color distribution and the detailed texture for each instance. Then, an image generator is designed to combine all of these instances to synthesize an image retaining texture and color. Besides, to generate more significant details, such as eyes, ears, and so on, we propose a novel technique called discriminative sketch augmentation, which can provide structural constraint by obtaining the sketch of the discriminative region. The extensive experiments demonstrate that our model not only generates convincing images but also achieves higher inception score and lower Fréchet Inception Distance on the MS-COCO dataset.

In this paper, a dual-independent-output inverter, which consists of four power switches, one inductor, and one capacitor, is proposed for segmented-track dynamic wireless power transfer (DWPT) system. It can generate two independently controllable outputs and operate in four output states, to drive two primary tracks independently. Moreover, the voltage gain ranges of both outputs of the proposed inverter are wider than that of a voltage-fed full-bridge inverter (VFFBI). These features enable the inverter to replace conventional VFFBI with less number of power switches and higher redundancy than the existing multi-output inverters to realize on-demand driving of the same number of primary tracks so as to simplify the design and control of the system. First, the topology and operating principle of the proposed inverter are introduced, and two output voltages are analyzed. Second, load voltage in different output states are analyzed, based on which the steady-state modulation strategy, output state switching strategy, and parameters of the proposed inverter are designed. Further, the soft switching state of the proposed inverter is also analyzed. Finally, a Matlab/Simulink simulation and an experimental setup are implemented to verify the correctness of the theoretical analysis and the feasibility and superiority of the proposed inverter.

Secret image sharing has been attracting considerable research attention in recent years as images become ubiquitous on the Internet and mobile applications. In traditional $(t, n)$ threshold secret image sharing schemes, the sender embeds the secret image into several shadow images and sends them to all participants. However, the shadow images are vulnerable during the transmission process on the Internet. In order to ensure the security of the shadow images which contain secret information, a new secret sharing scheme is proposed based on Faster region convolutional neural networks (Faster R-CNNs). This scheme uses a query image which does not have any secret information but looks similar to the original shadow image. Each participant retrieves the corresponding shadow image to search the query image in a big image database. As a result shadow images are searched by using Faster R-CNNs and stored in a database which is protected from being attacked, rather than transmitted over the network directly in the proposed scheme. The experimental results demonstrate that the proposed scheme can automatically retrieve the accurate shadow images by Faster R-CNNs and recover the secret image correctly.

Background/Aims: Although increased expression and gain function of transient receptor potential cation channel 6 (TRPC6) has been associated with the pathogenesis of some proteinuric glomerular diseases, it remains elusive how TRPC6 participates in the process of podocyte damage. Methods: The potential signaling responsible for TRPC6 activation was investigated using immunoblot assays in an in vitro podocyte injury model induced by Adriamycin (ADR). Podocyte apoptosis was measured using FITC-conjugated Annexin V and Propidium Iodide staining. The channel activity of TRPC6 was assessed using the Ca2+ influx assay. Results: Increase of TRPC6 expression was detected in ADR-treated podocytes, and TRPC6 knockdown significantly decreased ADR-induced podocytes apoptosis. Following ADR treatment, phospho-mTORSer2481 and phospho-AktSer473 was significantly increased in a time-dependent manner, whereas phospho-mTORSer2448 and phospho-p70S6KThr389 showed no change. ADR-induced apoptosis was prevented by ku0063794 (a dual mTOR complexes inhibitor), not by rapamycin (a specific mTORC1 inhibitor). Furthermore, nuclear translocation of NFκB/p65 was detected in ADR-treated podocytes, which was prevented by an Akt inhibitor triciribine. Of note, NFκB inhibitor PDTC prevented ADR-induced increase of TRPC6, and decreased ADR-induced apoptosis. We found that Akt activation and NFκB nuclear translocation was significantly inhibited by knockdown of mTORC2 protein Rictor, not by mTORC1 protein Raptor. In comparison with control, the Ca2+ influx was significantly increased in ADR-treated podocytes, which was remarkably prevented by TRPC6 knockdown. ADR-induced increase of TRPC6 channel activity was dramatically prevented by ku0063794, but not by rapamycin. Additionally, knockdown of Rictor, not Raptor, prevented ADR-induced increase of the Ca2+ influx. Moreover, the application of NFκB inhibitor PDTC also prevented the Ca2+ influx in ADR-treated podocytes. Conclusions: Our findings revealed that the mTORC2/Akt/NFκB pathway-mediated activation of TRPC6 participates in ADR-induced podocyte apoptosis.

Background:β-adrenoceptors play a crucial regulatory role in blood vessel endothelial cells. Isoprenaline (ISO, a β-adrenergic agonist) has been reported to promote angiogenesis through upregulation of vascular endothelial growth factor (VEGF) expression; however, the underlying mechanism remains to be investigated. It is widely accepted that certain noncoding RNAs, including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), can regulate endothelial cell behavior, including their involvement in angiogenesis. Therefore, we aimed to investigate whether noncoding RNAs participate in ISO-mediated angiogenesis using human umbilical vein endothelial cells (HUVECs). Methods: We evaluated VEGF-A messenger RNA (mRNA) and protein levels in ISO-treated HUVECs by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. To establish whether noncoding RNAs are associated with ISO-mediated angiogenesis, we measured expression of the miRNAs miR-210, miR-21, and miR-1, as well as that of the lncRNAs growth arrest-specific transcript 5 (GAS5), maternally expressed 3 (MEG3), and metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in HUVECs exposed to ISO. Furthermore, to ascertain its importance in ISO-mediated angiogenesis, we constructed the HUVECs with overexpressing miR-210 and detected the subsequent expression of VEGF-A and noncoding RNAs. All statistical analyses were performed using SPSS 16.0 software. Intergroup comparisons were carried out by one-way analysis of variance. Results: VEGF-A mRNA levels were elevated in the ISO group (1.57 ± 0.09) compared to those in the control group (P < 0.01). Moreover, concentrations of VEGF-A in culture supernatants significantly differed between the control (113.00 ± 19.21 pg/ml) and ISO groups (287.00 ± 20.27 pg/ml; P< 0.01). Expression of miR-1, miR-21, and miR-210 was higher (3.89 ± 0.44, 2.87 ± 087, and 3.33 ± 1.31, respectively) in ISO-treated cells than that in controls (P < 0.01), whereas that of GAS5 and MEG3 (0.22 ± 0.10 and 0.58 ± 0.16, respectively) was lower as a result of ISO administration (P < 0.05). There was no significant difference in the expression of MALAT1 between the groups. Interestingly, miR-210 overexpression heightened the levels of VEGF-A and miR-21 (5.87 ± 1.24 and 2.74 ± 1.15, respectively; P< 0.01) and reduced those of GAS5 and MEG3 (0.19 ± 0.01 and 0.09 ± 0.05, respectively; P< 0.01). Conclusions: ISO-mediated angiogenesis was associated with altered expression of miR-210, miR-21, and the lncRNAs GAS5 and MEG3. The effects of miR-210 on the expression of VEGF-A and noncoding RNAs were similar to those of ISO, indicating that it might play an important role in ISO-mediated angiogenesis.

Background: In this multi-institutional prospective study, we aimed to assess the safety and efficacy of nedaplatin plus S-1 (NS) chemotherapy for patients with recurrent and metastatic nasopharyngeal carcinoma (NPC) when platinum-containing regimens failed. Methods: A total of 52 recurrent and metastatic NPC patients who previously received, but failed with platinum-containing chemotherapy, had oral S-1 chemotherapy (twice daily from the first day to the fourteenth day) and nedaplatin (80 mg/ m 2 , day 1) every 3 weeks. The body surface area (BSA) decided the dose of S-1: 40 mg twice a day when BSA < 1.25 m 2 ; 50 mg twice daily when 1.25 m 2 ⩽ BSA < 1.5 m 2 ; and 60 mg twice daily when BSA ⩾ 1.5 m 2 . Results: Treatment was well tolerated. The main hematological adverse event was neutropenia. Five patients (9.6%) had grade 3 neutropenia. Three patients were found with grade 3 anemia (5.8%). One patient was found with grade 3 thrombocytopenia (1.9%). No patient was found with grade 3 or 4 nonhematological toxicity. The rates of complete response, partial response and overall response were 3.8%, 38.5% and 42.3%, respectively. Median time to progression was 6.2 months and median survival was 14.6 months. The rates of 1-year survival and 2-year survival were 63% and 27%, respectively. Conclusions: NS chemotherapy provides a satisfactory and safe clinical activity for patients with recurrent and metastatic NPC after platinum-containing chemotherapy failed.

Chlorination is the most popular method for disinfecting swimming pool water; however, although pathogens are being killed, many toxic compounds, called disinfection by-products (DBPs), are formed. Numerous epidemiological publications have associated the chlorination of pools with dysfunctions of the respiratory system and with some other diseases. However, the findings concerning these associations are not always consistent and have not been confirmed by toxicological studies. Therefore, the health effects from swimming in chlorinated pools and the corresponding stress reactions in organisms are unclear. In this study, we show that although the growth and behaviors of experimental rats were not affected, their health, training effects and metabolic profiles were significantly affected by a 12-week swimming training program in chlorinated water identical to that of public pools. Interestingly, the eyes and skin are the organs that are more directly affected than the lungs by the irritants in chlorinated water; instead of chlorination, training intensity, training frequency and choking on water may be the primary factors for lung damage induced by swimming. Among the five major organs (the heart, liver, spleen, lungs and kidneys), the liver is the most likely target of DBPs. Through metabolomics analysis, the corresponding metabolic stress pathways and a defensive system focusing on taurine were presented, based on which the corresponding countermeasures can be developed for swimming athletes and for others who spend a lot of time in chlorinated swimming pools.

The title compound, [Cu(C22H22N2O8)], is a tetradentate Schiff base complex. The CuII ion has a nearly square-planar geometry, being coordinated by two N atoms and two O atoms. The two chemically equivalent halves of the molecule are crystallographically independent. One of the carboxylic acid methyl ester units is located in the main plane of the molecule and the other is rotated by 65.3 (5)° with respect to this unit. In the crystal structure, there are π–π stacking interactions between adjacent six-membered chelate rings, with centroid-to-centroid distances of 3.602 (2) Å.