Search

The present study examines the gender–state dynamics in the Chinese context through a bottom-up approach by adopting an online survey method. We find four indicators, which are male priority, child suffering, gender ideology, marriage and fertility, could reflect one common factor—gender egalitarianism, and we utilize this scale to measure gender role attitudes among China's youth, as well as explore their psycho-political antecedents including system justification theory, national identification, and life satisfaction. The survey findings suggest a close interconnection between the construction of family and nation. The study's outcomes offer valuable insights into the ongoing progress and challenges relating to gender equality as perceived by young people in China. Furthermore, these findings establish a refined measurement instrument for future empirical studies in this domain. [ABSTRACT FROM AUTHOR]

Background: Limited data exists on the link between dietary iron intake and mortality in diabetes. Our investigation aimed to explore how dietary iron intake correlates with overall and cause-specific mortality in diabetic individuals. Methods: This analysis encompassed 5970 participants with diabetes from the National Health and Nutrition Examination Survey spanning 1999 to 2014. Baseline data were collected through surveys and examinations, with mortality status tracked via National Death Index records until December 31, 2015. Cox proportional hazard models were utilized to calculate hazard ratios (HR) and 95% confidence intervals (CI) for mortality from various causes, including cardiovascular disease (CVD) and cancer. Results: The average iron intake among the cohort was 14.1 ± 7.4 mg daily, with an average participant age of 61.3 and 3059 (51.3%) male adults. Over 41,425 person-years of follow-up, 1497 deaths were recorded. Following adjustments for multiple variables, an iron intake between 11.1 and 14.4 mg was associated with the lowest risk of all-cause mortality (HR 0.83 [0.70, 0.99], P < 0.05) compared to the reference group (<8.3 mg). Analysis of dose-response curves revealed an L-shaped pattern in men and a J-shaped pattern in women concerning the relationship between iron intake and all-cause mortality. Conclusions: Our findings suggest a nonlinear association between dietary iron intake and all-cause mortality in individuals with diabetes. Specifically, higher iron intake may increase all-cause mortality risk in men, while potentially exert a protective effect in women. [ABSTRACT FROM AUTHOR]

Aims: We aimed to develop an elaborative nomogram that predicts cancer-specific survival (CSS) in American and Chinese octogenarians treated with radical resection for CRC. Methods: The patient data of newly diagnosed patients aged 80 years or older who underwent radical resection for CRC from 2010 to 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database and then randomly divided into a training cohort and a validation cohort. The patients collected from our hospital were defined as the external validation cohort. Univariate and multivariate Cox regression was used to select independent predictive factors for the construction of a nomogram to predict 1-, 2- and 3-year CSS. Results: The multivariate Cox regression model identified age, T stage, N stage, perineural invasion, chemotherapy, tumour deposits, carcinoembryonic antigen level, number of lymph node metastases, and number of solid organ metastases as independent predictors of survival. The C-index of the nomogram for 1-, 2- and 3-year CSS was 0.758, 0.762, and 0.727, respectively, demonstrating significant clinical value and substantial reliability compared to the TNM stage. The calibration curve and area under the curve also indicated considerable predictive accuracy. In addition, decision curve analysis demonstrated desirable net benefits in clinical application. Conclusion: We constructed a nomogram for predicting the CSS of individual octogenarian patients with CRC who underwent radical resection. The nomogram performed better than the TNM staging system in this particular population and could guide clinicians in clinical follow-up and individual therapeutic plan formulation. Highlights: This study explored the exclusive characteristics of octogenarians treated with radical resection for colorectal cancer. This study is the first to develop a nomogram for predicting the cancer-specific survival of individual octogenarian patients after radical resection for colorectal cancer with the substantial reliability (C-index: 0.758 compared to the AJCC pathological staging system (C-index: 0.713). Internal validation of this nomogram in a cohort of American patients (N = 1644) and external validation in a cohort of Chinese patients (N = 368) confirmed its accuracy. [ABSTRACT FROM AUTHOR]

Tight glutenite reservoirs characterization and effective hydrocarbon-bearing formation identification faced great challenge due to ultra-low porosity, ultra-low permeability and complicated pore structure. Fracturing fracture-building technique always needed to obtain deliverability because of poor natural productive capacity. Pore structure characterization and friability prediction were essential in improving such type of reservoir evaluation. In this study, fractured tight glutenite reservoirs in Permian Jiamuhe Formation that located in northwest margin of Junggar Basin, northwest China, were chosen as an example, and 25 typical core samples were drilled and simultaneously applied for mercury injection capillary pressure (MICP), nuclear magnetic resonance (NMR) and whole-rock mineral X-ray diffraction experiments. A novel method of synthetizing pseudo-pore-throat radius (Rc) distribution from porosity frequency spectra was established to characterize fractured formation pore structure. Quartz and calcite were considered as the fragile mineral, and rock mineral component ratio method was used to predict brittleness index. Meanwhile, the statistical model raised by Jin et al. (SPE J 20:518–526, 2015) was used to predict two types of fracture toughness. And then, brittleness index and fracture toughness were combined to characterize tight glutenite reservoirs friability. Combining with maximal pore-throat radius (Rmax, reflected rock pore structure) and friability, our target formations were classified into four clusters. In addition, relationships among pore structure, friability and daily hydrocarbon production per meter (DI) were analyzed, and a model to predict DI from well-logging data was established. Comparison of predicted DI with the extracted results from drill stem test (DST) data illustrated the reliability of our raised models. This would be valuable in determining optimal hydrocarbon production intervals and formulating reasonable developed plans. [ABSTRACT FROM AUTHOR]

Ammonium perchlorate (AP) is a commonly used oxidant for rocket solid propellants. To control the thermal decomposition of AP, a new PEI-imidazole derivative (PEI-ICA) was synthesized. With the combination of Cu compound, the heat decomposition behavior of the AP's composites was tuned, and the activation energy was also reduced. To explore the potential reason for the catalytic effect, a series of measurements were also carried out, which indicates the electrostatic self-assembly of PEI-ICA and its combination with Cu compound should be responsible for the different heat decomposition behavior of AP. [ABSTRACT FROM AUTHOR]

Small-scale Solid Waste Thermal Treatment (SSWTT) is prevalent in remote Chinese locations. However, the ecological threats associated with heavy metals in resultant bottom ash remain undefined. This research study scrutinized such ash from eight differing sites, assessing heavy metal content, chemical form, and leaching toxicity. Most bottom ash samples met soil contamination standards for development land (GB36600-2018). However, levels of As, Cd, Cr, Cu, Ni, Pb, and Zn in some samples exceeded agricultural land standards GB15618-2018) by 1591%, 64,478%, 1880%, 3886%, 963%, 1110%, and 2011% respectively. Additionally, the As and Cd contents surpassed the construction land control limit value by 383% and 13% respectively. The mean values of the combined oxidizable and residual fraction (F3 + F4) for each heavy metal in all samples exceeded 65%, with Cr, Cu, Ni, and Pb reaching over 95%. All sample leaching concentrations, obtained via the HJ/T 299 procedure, were less than limits set by the identification standards for hazardous wastes (GB5085.3–2007). However, only the leaching concentrations of three samples via the leaching procedure HJ/T 300 met the "Solid Waste Landfill Pollution Control Standard" (GB 16889–2008). The results indicate that the location and type of SSWTT equipment play a crucial role in determining an appropriate solution for bottom ash management. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the association between circulating osteocalcin and incident cardiovascular diseases in a community-based cohort, and further assess whether the association differs by different glycemic stages. Methods: This cohort study included 1428 participants (626 men and 802 women) aged 50–80 years, without baseline cardiovascular diseases, and with osteocalcin data available. Circulating total osteocalcin levels were measured by electrochemiluminescence immunoassay. Multivariate Cox proportional hazards models were used to assess the relationship between osteocalcin levels and different glycemic stages with cardiovascular events. Results: At baseline, 437 participants were normoglycaemia and 991 participants were hyperglycaemia. Median circulating osteocalcin levels were 16.43 (13.34–20.19) and 21.66 (17.95–26.11) ng/mL in men and women, respectively. During a mean follow-up of 7.6 years, 144 cases of cardiovascular diseases occurred (10.1%). The risk of incident cardiovascular diseases linearly increased with a decrease in baseline osteocalcin quartiles (quartile 1 versus quartile 4: hazard ratio 2.44, 95% confidence interval 1.07–5.55) in women, while not in men (Pinteraction on sex = 0.028). Subgroup analyses showed that the association was more predominant in participants with baseline hyperglycaemia. Besides, the joint effect of baseline decreased osteocalcin levels and hyperglycaemia resulted in higher risks of future cardiovascular diseases. Conclusions: Low baseline osteocalcin levels were associated with high risks of cardiovascular diseases in middle-aged and elderly women, which were more predominant among those with baseline hyperglycaemia. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to evaluate the performance of noninvasive prenatal testing (NIPT) for the detection of chromosomal aneuploidies and copy number variations (CNVs) in twin pregnancies. Method: A cohort of 2010 women with twin pregnancies was recruited. 1331 patients opted for NIPT, and 679 patients opted for expanded NIPT (NIPT-plus). All high-risk patients were advised to undergo invasive prenatal diagnosis. All participants were followed up until 6 months after birth. Results: Twenty-two cases were predicted to have a high risk of chromosome abnormalities by NIPT, of which 14 pregnant women underwent invasive prenatal diagnosis. The 14 cases included 3 cases of trisomy 21, 1 case of trisomy 18, 1 case of trisomy 7, 2 cases of sex chromosome aneuploidies (SCAs), and 7 cases of CNVs, of which the confirmed cases numbered 2, 1, 0, 1, and 0, respectively. Twenty cases were predicted to have a high risk of chromosome abnormalities by NIPT-plus, of which 16 pregnant women underwent invasive prenatal diagnosis. The 16 cases included 1 case of trisomy 21, 1 case of trisomy 7, 7 cases of SCAs, and 7 cases of CNVs, of which were confirmed in 1, 0, 3, and 2, respectively. No false-negative result was reported during the follow-up period. Conclusion: The NIPT/NIPT-plus has excellent performance in the detection of chromosome aneuploidies in twin pregnancies. But for CNVs, the effectiveness of NIPT is poor, and the NIPT-plus have a certain detection efficiency. It is worth noting that pre- and post-genetic counseling is especially important, and the chorionicity, mode of conception, clinical indications, and fetal fraction should be considered as influencing factors. [ABSTRACT FROM AUTHOR]

Long non-coding RNA Small Nucleolar RNA Host Gene 16 (SNHG16) has been reported to participate in Lipopolysaccharide (LPS)-induced inflammatory pathway, which contributes to pneumonia. This study was therefore conducted to explore the role of SNHG16 in pneumonia. In this study, expression of SNHG16 and microRNA (miR)-210 in pneumonia plasma samples (n = 56) and control samples (n = 60) was detected by RT-qPCR. The potential crosstalk between SNHG16 and miR-210 was analyzed by performing overexpression experiments. MSP was performed to study the role of SNHG16 in methylation of miR-210 gene. Cell apoptosis was analyzed by cell apoptosis assay. Decreased expression levels of SNHG16 and increased expression levels of miR-210 were observed in pneumonia. SNHG16 showed an inverse correlation to miR-210. LPS treatment led to downregulated SNHG16 and upregulated miR-210 in Human Bronchial Epithelial Cells (HBEpCs). In HBEpCs, SNHG16 downregulated miR-210 and increased miR-210 DNA gene methylation. Moreover, SNHG16 suppressed the role of miR-210 in cell apoptosis under LPS treatment. In conclusion, SNHG16 is downregulated in pneumonia, and it downregulates miR-210 possibly through methylation to promote lung cell apoptosis induced by LPS. [ABSTRACT FROM AUTHOR]

Nitrates can stimulate the biosynthesis of hydrophilic yellow pigments (HYPs) in Monascus ruber CGMCC 10910. To explore the molecular mechanisms whereby nitrates (NaNO3 and NH4NO3) regulate HYP production, an integrated transcriptomic and proteomic analysis was conducted in this study. Nitrate addition led to an approximately 75% higher HYP production compared with the untreated group, especially compounds Y3 and Y4. Comparative transcriptomic analysis found that mpigsA, H, K, L, and P genes involved in yellow pigment biosynthesis were significantly upregulated. In addition, pigment biosynthesis-related (carbon catabolism, amino acid metabolism, polyketide synthesis, and fatty acid metabolism) genes were upregulated to provide precursors and energy for HYP biosynthesis and cell growth. Secretion-related (cytomembrane ergosterol biosynthetic, and transport) pathways were also noticeably regulated to accelerate transmembrane transport of HYPs. Meanwhile, proteomic analysis showed that nitrates improved the protein expression of hybrid polyketide synthase-nonribosomal peptide synthetase, oxidoreductase, glucoamylase, endo-1,4-beta-xylanase, O-acetylhomoserine, and isocitrate lyase to enhance HYP production. These findings demonstrated the regulatory mechanism of nitrates for enhancing HYP production in Monascus. Key points: • Nitrates stimulated the biosynthesis of Monascus hydrophilic yellow pigments (HYPs) • Nitrates affected transcriptional level of pigment biosynthesis- and transport genes • Increased expression of hybrid PKS-NRPS and transporters promoted production of HYPs [ABSTRACT FROM AUTHOR]

Toxic polycyclic aromatic hydrocarbons (PAHs) are often released into the environment during the combustion and processing of fossil fuels and are capable of causing significant pollution to people and the environment. One of the representative substances of PAHs is phenanthrene, which is often studied as a model compound for PAHs treatment. In this study, we compared the results of transcriptome analysis of Pseudomonas stutzeri LH-42 in two different culture conditions under phenanthrene-induced culture (test group) and glucose-induced culture (control group), and analysed the key enzymatic mechanisms of Pseudomonas stutzeri LH-42 in the biodegradation of phenanthrene. In our experiments, the transcriptome results showed that a total of 380 genes were more than twofold differentially expressed in the test group, of which 187 genes were significantly up-regulated in expression under Phenanthrene induction. Among the 380 differentially expressed genes, 90 genes were involved in Phenanthrene biodegradation, mainly including genes involved in biometabolism, cellular chemotaxis, substrate transport, signal induction and other related processes. Based on the transcriptome sequence analysis of Pseudomonas stutzeri LH-42 at the time of phenanthrene induction, a total of 25 dioxygenase genes were identified, and the related genes were mainly concentrated in two relatively concentrated clusters of PAHs biodegradation genes. The transcriptome analysis resulted in a complete set of enzyme genes related to the phenanthrene biodegradation pathway. The analysis of key enzymes led to the inference of a possible phenanthrene biodegradation pathway: the salicylic acid degradation pathway. The results of this study provide a theoretical basis for in situ remediation of PAHs-contaminated environments using Pseudomonas stutzeri LH-42. [ABSTRACT FROM AUTHOR]

The self-driven articulated arm coordinate measuring machine (self-driven AACMM) is a new type of flexible coordinate measuring equipment. The integrated joint module is introduced to the AACMM joint for self-driven control and automatic measurement, resulting in the joint angle error of self-driven AACMM. In this study, an ideal measurement model of the self-driven AACMM have been established. The sources of angle error of joint module is analysed, and single and comprehensive models of the joint module's angle error are established. Numerical simulation of the angle error model of the single joint module is conducted by MATLAB. An angle error calibration experiment of the joint module is carried out with the photoelectric autocollimator and the metal 36-sided prism. Results show that each joint module produces different torsional deformation due to load. The angle error of joint module 1, 6 are most and least affected by the load torque, the actual average errors of the two are 37.64 arcsec and −0.9632 arcsec, respectively. The simulated and calibrated single-joint module angle error trends are cyclical, and the calibrated angle error range is [−100.4 arcsec, 205.2 arcsec]. The harmonic error component in the harmonic reducer and the magnetic encoder is an important factor of the angle error of joint module. The eatablished angle error model of single joint module can be effiectively applied to comprehensive error compensation for high measurement accuracy of self-driven AACMM. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the efficacy and safety of a novel balloon catheter in dilation intervention for patients with cricopharyngeus achalasia after stroke. Thirty-four patients with cricopharyngeus achalasia after stroke received routine swallowing rehabilitation training and were randomly assigned to an experimental group (Exp, n = 17) that received dilation therapy using the novel balloon catheter once daily for 5 days per week or a control group (Con, n = 17) that received dilation therapy with a 14-Fr ordinary urinary catheter once daily for 5 days per week. The intervention duration, Eating Assessment Tool (EAT)-10 scores, and Functional Oral Intake Scale (FOIS) scores were recorded at baseline and each day during intervention. The time for a patient's FOIS score to be ≥ 3 as well as the recovery time for oral intake of water, liquid food, mushy food, and solid food were recorded or estimated. Complications were also recorded during intervention. The intervention duration was shorter in the Exp group than in the Con group (p = 0.005). The Exp group patients improved faster than the Con group patients, with a shorter recovery time for oral intake of liquid food (p = 0.002), mushy food (p = 0.001), and solid food (p = 0.001). At the time of intervention termination, EAT-10 scores were lower in the Exp group than in the Con group (p = 0.005). The Exp group had a similar incidence of complications as the Con group but with better tolerability (p = 0.028). Compared with the urinary catheter, the novel balloon catheter for dilation in patients with cricopharyngeus achalasia after stroke may lead to a better and more rapid recovery. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to establish two preoperative nomograms to evaluate the risk for axillary lymph node (ALN) metastasis in early breast cancer patients based on ultrasonographic-clinicopathologic features. Methods: We prospectively evaluated 593 consecutive female participants who were diagnosed with cT1-3N0-1M0 breast cancer between March 2018 and May 2019 at Sun Yat-Sen Memorial Hospital. The participants were randomly classified into training and validation sets in a 4:1 ratio for the development and validation of the nomograms, respectively. Multivariate logistic regression analysis was performed to identify independent predictors of ALN status. We developed Nomogram A and Nomogram B to predict ALN metastasis (presence vs. absence) and the number of metastatic ALNs (≤ 2 vs. > 2), respectively. Results: A total of 528 participants were evaluated in the final analyses. Multivariable analysis revealed that the number of suspicious lymph nodes, long axis, short-to-long axis ratio, cortical thickness, tumor location, and histological grade were independent predictors of ALN status. The AUCs of nomogram A in the training and validation groups were 0.83 and 0.78, respectively. The AUCs of nomogram B in the training and validation groups were 0.87 and 0.87, respectively. Both nomograms were well-calibrated. Conclusion: We developed two preoperative nomograms that can be used to predict ALN metastasis (presence vs. absence) and the number of metastatic ALNs (≤ 2 vs. > 2) in early breast cancer patients. Both nomograms are useful tools that will help clinicians predict the risk of ALN metastasis and facilitate therapy decision-making about axillary surgery. Key Points: • We developed two preoperative nomograms to predict axillary lymph node status based on ultrasonographic-clinicopathologic features. • Nomogram A was used to predict axillary lymph node metastasis (presence vs. absence). The AUCs in the training and validation groups were 0.83 and 0.78, respectively. Nomogram B was used to estimate the number of metastatic lymph nodes (≤ 2 vs. > 2). The AUCs in the training and validation group were 0.87 and 0.87, respectively. • Our nomograms may help clinicians weigh the risks and benefits of axillary surgery more appropriately. [ABSTRACT FROM AUTHOR]

To evaluate and establish a prediction model of the outcome of induced labor based on machine learning algorithm. This was a cross-sectional design. The subjects were divided into primipara and multipara, and the risk factors for the outcomes of induced labor were assessed by multifactor logistic regression analysis. The outcome model of labor induced with oxytocin (OT) was constructed based on the four machine learning algorithms, including AdaBoost, logistic regression, naive Bayes classifier, and support vector machine. Factors, such as accuracy, recall, precision, F1 value, and receiver operating characteristic curve, were used to evaluate the prediction performance of the model, and the clinical application of the model was verified. A total of 907 participants were included in this study. Logistic regression algorithm obtained better results in both primipara and multipara groups compared to the other three models. The accuracy of the model for the prediction of "successful induction of labor" was 94.24% and 96.55%, and that of "failed induction of labor" was 65.00% and 66.67% in the primipara and the multipara groups, respectively. This study established a prediction model of OT-induced labor based on the Logistic regression algorithm, with rapid response, high accuracy, and strong extrapolation, which was critical for obstetric clinical nursing. [ABSTRACT FROM AUTHOR]

Although two-dimensional (2D) layered double hydroxides (LDHs) have been widely used as efficient nanoagents for biological diagnosis and treatment, they have been found to be inert as photosensitizers (PSs) for photodynamic therapy (PDT). Herein, we report the defect engineering of ultrathin 2D CoMo-LDH and NiMo-LDH nanosheets as highly active inorganic PSs for PDT in the third near-infrared (NIR-III) window. Hydrothermal-synthesized 2D CoMo-LDH and NiMo-LDH nanosheets are etched via a simple acid treatment to obtain defect-rich CoMo-LDH and NiMo-LDH nanosheets. Importantly, the defect-rich CoMo-LDH nanosheets exhibit much higher activity (~97 times) for generation of reactive oxygen species than that of the pristine CoMo-LDH nanosheets under a NIR-III 1567 nm laser irradiation. Therefore, after modification with polyethylene glycol, the defect-rich CoMo-LDH nanosheets can be used as an efficient inorganic PS for PDT to efficiently induce cancer cells apoptosis in vitro and eradicate tumors in vivo under 1567 nm laser irradiation. Defect engineering of 2 dimensional layered double hydroxide sheets improves their photocatalytic activity. Here, the authors etch sheets in acid and show that the etched sheets generate substantially more reactive oxygen species that untreated sheets and the treated sheets can be used to kill cancer cells in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Neuropathic pain is one of the most common conditions requiring treatment worldwide. Salidroside (SAL), a phenylpropanoid glucoside extracted from Rhodiola, has been suggested to produce an analgesic effect in chronic pain. However, whether SAL could alleviate pain hypersensitivity after peripheral nerve injury and its mode of action remains unclear. Several studies suggest that activation of the spinal NOD-like receptor protein 3 (NLRP3) inflammasome and its related proteins contribute to neuropathic pain's pathogenesis. This study investigates the time course of activation of spinal NLRP3 inflammasome axis in the development of neuropathic pain and also whether SAL could be an effective treatment for this type of pain by modulating NLRP3 inflammasome. In the chronic constriction injury (CCI) mice model, spinal NLRP3 inflammasome-related proteins and TXNIP, the mediator of NLRP3, were upregulated from the 14th to the 28th day after injury. The TXNIP and NLRP3 inflammasome-related proteins were mainly present in neurons and microglial cells in the spinal dorsal horn after CCI. Intraperitoneal injection of SAL at 200 mg/kg for 14 consecutive days starting from the 7th day of CCI injury could ameliorate mechanical and thermal hypersensitivity in the CCI model. Moreover, SAL inhibited the activation of the TXNIP/NLRP3 inflammasome axis and mitigated the neuronal loss of spinal dorsal horn induced by nerve injury. These results indicate that SAL could produce analgesic and neuroprotective effects in the CCI model of neuropathic pain. [ABSTRACT FROM AUTHOR]

The immune context of the tumor microenvironment (TME) is critical for effective immunotherapy. Nonetheless, DNA-based biomarkers for the immune-sensitive TME and the identification of immune checkpoint inhibitor (ICI) responders are under-explored. This study aims to comprehensively landscape the homologous recombination deficiency (HRD) score, an emerging hallmark for tumor genome instability that triggers immune responsiveness across major cancer types, and to unveil their link to the TME and immunotherapeutic response. The HRD-associated genomic scars were characterized in 9088 tumor samples across 32 cancer types from TCGA. We evaluated the HRD score's performance in classifying ICI responders using an independent breast cancer cohort (GSE87049) and 11 in vivo murine mammary tumor models treated with anti-PD1/CTLA4 regimen (GSE124821). This study revealed a broad association between HRD-high genotype and neoantigenesis in the major cancer types including bladder cancer, breast cancer, head and neck squamous carcinoma, lung adenocarcinoma, lung squamous cell carcinoma, ovarian cancer, and sarcoma. Tumors with high HRD score bears increased leukocyte infiltration and lymphocyte fraction and demonstrated immune-sensitive microenvironment. The tumor immune dysfunction and exclusion (TIDE) model further confirmed HRD score-high genotype as a potential predictor for ICI immunotherapy responders in breast cancer. In conclusion, tumors with high HRD score exhibit an immune-sensitive TME. The HRD-high genotype is a promising marker for identifying ICI therapy responders among breast cancer patients. [ABSTRACT FROM AUTHOR]

DNA methylation and demethylation play an important role in neuropathic pain. In general, DNA methylation of CpG sites in the promoter region impedes gene expression, whereas DNA demethylation contributes to gene expression. Here, we evaluated the methylation status of CpG sites in genomic DNA promoter regions in dorsal root ganglions (DRGs) of diabetic neuropathic pain (DNP) mice. In our research, streptozotocin (STZ) was intraperitoneally injected into mice to construct DNP models. The DNP mice showed higher fasting blood glucose (above 11.1 mmol/L), lower body weight, and mechanical allodynia than control mice. Whole-genome bisulfite sequencing (WGBS) revealed an altered methylation pattern in CpG sites in the DNA promoter regions in DRGs of DNP mice. The results showed 376 promoter regions with hypermethylated CpG sites and 336 promoter regions with hypomethylated CpG sites. In addition, our data indicated that altered DNA methylation occurs primarily on CpG sites in DNA promoter regions. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that differentially methylated CpG sites annotated genes were involved in activities of the nervous and sensory systems. Enrichment analysis indicated that genes in these pathways contributed to diabetes or pain. In conclusion, our study enriched the role of DNA methylation in DNP. [ABSTRACT FROM AUTHOR]

Objective: To speculate whether induction chemotherapy (IC) or adjuvant chemotherapy (AC) with concurrent chemoradiotherapy (CCRT) could obtain better survival benefit for stage III or IV locally advanced nasopharyngeal carcinoma (LA-NPC). Methods: Only randomized controlled trials were incorporated. There were five treatments (CCRT, IC + CCRT, CCRT + AC, IC + RT and RT alone) recruited for analysis. Overall survival (OS), locoregional recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS) with a hazard ratio (HR) were selected as endpoints. First of all, we performed a traditional meta-analysis and subsequently conducted network meta-analysis based on the Bayesian method. Results: Totally, 15 studies, including 6182 patients, were incorporated for analysis. There was a statistically significant benefits in favor of IC + CCRT, compared with CCRT alone, for OS [HR = 0.75, 95% CI = 0.63–0.89], LRFS [HR = 0.70, 95% CI = 0.56–0.86], and DMFS [HR = 0.65, 95% CI = 0.54–0.78]. What's more, we did not observed any significant differences between CCRT + AC and CCRT alone for all the endpoints. Unsurprisingly, it was RT alone that demonstrate the poorest survival benefit. Strange to say, survival benefit, between IC + CCRT and IC + RT, or between IC + CCRT and CCRT + AC, did not significantly exist. Conclusion: Induction chemotherapy IC + CCRT provided better survival benefit than CCRT alone. CCRT + AC failed to increase survival benefit significantly compared to CCRT alone. More research about comparing IC + CCRT with IC + RT or CCRT + AC are needed. [ABSTRACT FROM AUTHOR]

To curb the spread of the coronavirus, China implemented lockdown policies on January 23, 2020. The resulting extreme changes in human behavior may have influenced the air pollutants concentration. However, despite these changes, hazy weather persisted in Shanghai and became a public issue. This study aims to investigate air pollutant mass concentration changes during the lockdown in Shanghai. Air pollutant mass concentration data and meteorological data during the pre-lockdown period and the level I response lockdown period were analyzed by statistical analysis and a Lagrangian particle diffusion model. The data was classified in three periods: P1 (pre-lockdown: 10 days before the Spring Festival), P2 (the first 10 days after lockdown: during the Spring Festival celebration), and P3 (the second 10 days after lockdown: after the Spring Festival). Data for the same period in 2019 were used as a reference. The results indicate that the Spring Festival holiday in 2019 resulted in a reduction in energy consumption, which led to a decrease in PM2.5 (26.4%) and NO2 (43.41%) mass concentration, but an increase in ozone mass concentration (31.39%) in P2 compared with P1. The integrated effect of the Spring Festival holiday and lockdown in 2020 resulted in a decrease in PM2.5 (36.5%) and NO2 (51.9%) mass concentrations, but an increase in ozone mass concentration (43.8%) in P2 compared with P1. After the Spring Festival, the mass concentrations of PM2.5, SO2, and NO2 increased by 74.41%, 5.52%, and 53.28%, respectively in P3 compared with P2 in 2019. However, PM2.5 and SO2 concentrations in 2020 continued to decrease, by 14.74% and 4.61%, respectively, while NO2 mass concentration increased by 7.82% in P3 compared with P2. We also found that PM2.5 mass concentration is susceptible to regional transmission from the surrounding cities. PM2.5 and other gaseous pollutants show different correlations in different periods, while NO2 and O3 always show a strong negative correlation. The principal components before the Spring Festival in 2019 were O3 and NO2, and after the Spring Festival, they were PM2.5 and CO, while the principal components before the lockdown in 2020 were PM2.5 and CO, and during lockdown they were O3 and NO2. [ABSTRACT FROM AUTHOR]

Permeability is an important input parameter in evaluating formation validity and predicting deliverability; its value is always estimated from porosity or other formation parameters based on the statistical methods. However, glutenite reservoir permeability prediction faces a great challenge due to the strong heterogeneity. In this study, to establish a reasonable model to predict heterogeneous glutenite reservoir permeability, 483 core samples were recovered from the Permian Jiamuhe Formation, Shawan Depression, northwestern Junggar Basin, China for routine physical property experiments; 21 of them were chosen to apply for laboratory nuclear magnetic resonance (NMR) measurements. After introducing the hydraulic flow unit (HFU) theory, these 483 core samples are classified into eight categories based on the flow zone indicator (FZI) difference, and applicative relationships of core-derived porosity and permeability are respectively established for every type of core sample. Meanwhile, based on the deeply analyzing of the expression of FZI and the classic Timur-Coates permeability-based model, a theoretical model of calculating FZI from NMR data is proposed. The involved input parameters are calibrated by using the experimental data of 21 core samples. After the established models are extended into field applications, the consecutive FZI curve is estimated from NMR logging to classify formations, and the corresponding relationships are used to predict permeability. Comparisons of the predicted FZI and permeability with core-derived results verify the reliability of the proposed models. They can be well used to precisely predict permeability in our target heterogeneous glutenite reservoirs. [ABSTRACT FROM AUTHOR]

Background: With more and more medical device databases being developed, there is an increasing interest in learning the geographical patterns of medical-device-related adverse events (AEs). For a specific medical device and an adverse event (AE) of interest, our aim is to detect a spatial-cluster signal that has a significantly higher AE rate than the AE rates for other regions, when the exposure information is available. Methods: We develop a likelihood ratio test (LRT) method incorporating exposure information, by geographical region, for spatial-cluster signal detection when the underlying observed health outcome associated with the medical device of interest is a Poisson-modeled count data (e.g., an outcome of AE count). Results: An extensive simulation study shows that this method has good power, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). The application of the method is demonstrated by two hypothetical case studies regarding a medical device that is used for patients who have reached end-stage heart failure. Discussion: A methodological framework for exploring geographic patterns in device safety surveillance is discussed, including safety data collection, statistical tools, and display of the analysis results. The proposed statistical method can be used for spatial-cluster signal detection for an AE of interest from medical device registries or other databases that have patient-level geographical information. [ABSTRACT FROM AUTHOR]

Background: With a record number of medical devices approved or cleared, it is important to understand the performance of devices once they are on the market. Using data from multiple medical devices and multiple sites, the problem of interest in this article is to detect if a device is a signal; that is, if a device performs significantly different from other devices of the same class, when the outcome of interest is a continuous variable. Methods: We develop a normal likelihood ratio test (LRT) method, henceforth referred to as normal-LRT, by incorporating sample size information into the methodological framework, to detect device signals using multi-site and multi-device data. Results: It is shown via extensive simulation that the proposed method controls the type-I error and false discovery rate (FDR), while having good power and sensitivity. This method is applied to a hypothetical case study, in which 6 medical devices of the same class are compared. Discussion: The normal-LRT method can be considered as a tool for device signal detection using data from multi-site and multi-device when the outcome of interest is a continuous measurement. [ABSTRACT FROM AUTHOR]

The efficacy of targeted therapy is associated with multi-gene mutation status. Carrying out effective multi-genotyping analysis in combination has been a challenge in clinical settings. We therefore developed a droplet-based capillary electrophoresis (CE) system coupled with PCR-restriction fragment length polymorphism (PCR-RFLP) technology to detect multi-gene mutations from a small volume of samples. A 16 × 16 200-nL droplet array for sample encapsulation was constructed on a glass chip. The electrophoresis system consisted of a tapered vertical capillary filled with polyvinylpyrrolidone, a laser-induced fluorescence detector, and a high voltage power supply. Notably, a droplet-based electrokinetic sample introduction method and a "∩" shape capillary were developed to facilitate consecutive droplet sampling using a home-made automatic control module. The DL2000 DNA marker was consecutively separated, achieving high migration time and plate number reproducibility. The system was further applied to detect PCR-RFLP products. For colorectal cancer (CRC) cell lines, KRAS, BRAF, and PIK3CA were genotyped with a sensitivity of 0.25%. For CRC patient specimens, 30 samples were consecutively and automatically multi-genotyped without inter-sample contamination, with a lowest mutation frequency of 0.37%. For the first time, we developed a droplet-based CE system for consecutive DNA analysis with low sample consumption. This automated CE system could be further developed to integrate the full process of gene mutation detection, serving as a more effective platform for individualised therapy. [ABSTRACT FROM AUTHOR]

Natural halloysite nanotubes (HNTs) with a hollow lumen have been widely applied in many fields, such as water purification, drug carriers, cosmetics, antibacterial, and scaffolds for tissue engineering. However, their in vivo toxicity is still largely unclear. The aim of this study is to evaluate sub-chronic oral toxicity of HNTs in the small intestine of mice. The results demonstrated that oral HNTs at low dose (5 mg/kg) for 30 days promoted mouse growth with no obvious adverse effect on the small intestine. The promotive effect on mouse growth disappeared after cessation of oral administration of HNTs. Oral HNTs at high dose (50 mg/kg) for 30 days induced aluminum (Al) and silicon (Si) accumulation and oxidative stress in the small intestine, which caused significant increases in the levels of cyclooxygenase-2 (COX-2) and nitric oxide synthase (iNOS) and inflammatory response and iNOS-mediated damages in the organ. Oral HNTs-induced changes in the small intestine at high dose were not observed after a 30-day recovery period. These findings provided the first evidence that oral HNTs-induced sub-chronic toxicity in the small intestine was reversible. The results suggest that HNTs at low concentration in environments have no adverse effect on mice, while there are health risks to mice under severe contamination by HNTs. [ABSTRACT FROM AUTHOR]

The activity of proteins rather than the concentration of proteins in biopharmaceutical and in vitro diagnostics are often the primary focus. Nonetheless, development of a calibration-free concentration analysis (CFCA) approach that accurately quantifies the concentration of proteins based on molecular interactions with specific monoclonal antibodies and without the requirement of external calibrators would be beneficial to diagnostics. Generally, only analytes that interact with the antibody (Ab) are quantified by CFCA. Moreover, protein concentrations measured by CFCA usually vary when different Abs are used, and are lower than those obtained by amino acid analysis because any non-native state population of the target protein is not captured by the Ab. To achieve comparable results between CFCA and traditional amino acid analysis (AAA), an Ab that recognizes the target protein irrespective of its conformation should be used. In this report, three different monoclonal antibodies were used to quantify purified human myoglobin in solution by CFCA. The concentrations obtain by the Abs (i.e., 2.985, 2.912, 3.032 mg mL−1) were comparable with that obtained by AAA. Moreover, isotope dilution mass spectrometry (IDMS) gave a human myoglobin concentration of 2.851 mg mL−1, which is also in agreement with the results from CFCA. The performance of CFCA was evaluated by measuring various parameters, including within-day and between-day precision. The results demonstrated that the active concentration measured by CFCA is comparable with that of IDMS when the appropriate Ab is used. Recommended procedures for performing the new CFCA approach are provided. This study shows that CFCA represents a primary method for accurate protein concentration determination, which should aid the development of certified reference materials. [ABSTRACT FROM AUTHOR]

The precise circuit of the substantia nigra pars reticulata (SNr) involved in temporal lobe epilepsy (TLE) is still unclear. Here we found that optogenetic or chemogenetic activation of SNr parvalbumin+ (PV) GABAergic neurons amplifies seizure activities in kindling- and kainic acid-induced TLE models, whereas selective inhibition of these neurons alleviates seizure activities. The severity of seizures is bidirectionally regulated by optogenetic manipulation of SNr PV fibers projecting to the parafascicular nucleus (PF). Electrophysiology combined with rabies virus-assisted circuit mapping shows that SNr PV neurons directly project to and functionally inhibit posterior PF GABAergic neurons. Activity of these neurons also regulates seizure activity. Collectively, our results reveal that a long-range SNr-PF disinhibitory circuit participates in regulating seizure in TLE and inactivation of this circuit can alleviate severity of epileptic seizures. These findings provide a better understanding of pathological changes from a circuit perspective and suggest a possibility to precisely control epilepsy. The neural circuits through which the substantia nigra pars reticulata (SNr) exerts its role in epilepsy control are not known. Here the authors reveal that a long-range SNr-parafascicular nucleus disinhibitory circuit participates in regulating seizures in temporal lobe epilepsy and inhibition of this circuit can alleviate severity of epileptic seizures. [ABSTRACT FROM AUTHOR]

In 2014, J. Pipan and M. Schechter discussed periodic solutions for second-order Hamiltonian systems with resonance. In this paper, we will generalize their results. To this end, we will first establish an index theory for second-order linear Hamiltonian systems with coefficient matrix in L 1 . Then we propose generalized assumptions. We also investigate multiple solutions for symmetric second-order Hamiltonian systems. [ABSTRACT FROM AUTHOR]

The engine starting process presents high particulate emissions in exhaust. This study gives a systematic investigation on particulate emission characteristics, including particulate matter (PM) mass, soluble organic fraction (SOF) mass, C10-C26 n-Alkanes and particle-bound polycyclic aromatic hydrocarbons (PAHs), that have been emitted from a gasoline direct injection (GDI) engine measured by Gas chromatography-mass spectrometry during starting period. The results show that particulate emissions under the warm coolant start condition decline dramatically compared with the cold start condition. 90 % of particulate number (PN) emitted during the cold and warm start periods generally are nucleation-mode particles. Over 50 % PM mass and PAHs emissions are emitted in the first 0–13 s stage. SOF mass accounts more than 60 % in PM mass emissions, especially under the warm coolant start condition. Some C23–C26 n-Alkanes are detected under the cold start condition which demonstrates that partial particulate composition directly comes from lubricant. The concentration of the two ring PAHs is the lowest among PAHs while the four to six ring PAHs are higher under the cold start operation. The toxicity of PAHs which is evaluated by Benzo(a)pyrene equivalent toxicity (BEQ) value of the total PAHs emissions shows a decline of 66.83 % under the warm start condition. [ABSTRACT FROM AUTHOR]

In this paper, we will first establish an index theory for second order linear Hamiltonian systems with L1 coefficient matrix satisfying generalized periodic boundary value conditions. And then we will investigate nontrivial solutions for asymptotically linear second-order Hamiltonian systems and obtain some new results. [ABSTRACT FROM AUTHOR]

Key message: Loss of function of a mitochondrial complex I subunit (OsNDUFA9) causes abnormal embryo development and affects starch synthesis by altering the expression of starch synthesis-related genes and proteins.Abstract: Proton-pumping NADH: ubiquinone oxidoreductase (also called complex I) is thought to be the largest and most complicated enzyme of the mitochondrial respiratory chain. Mutations of complex I subunits have been revealed to link with a number of growth inhibitions in plants. However, the function of complex I subunits in rice remains unclear. Here, we isolated a rice floury endosperm mutant (named flo13) that was embryonic lethal and failed to germinate. Semi-thin sectioning analysis showed that compound starch grain development in the mutant was greatly impaired, leading to significantly compromised starch biosynthesis and decreased 1000-grain weight relative to the wild type. Map-based cloning revealed that FLO13 encodes an accessory subunit of complex I protein (designated as OsNDUFA9). A single nucleotide substitution (G18A) occurred in the first exon of OsNDUFA9, introducing a premature stop codon in the flo13 mutant gene. OsNDUFA9 was ubiquitously expressed in various tissues and the OsNDUFA9 protein was localized to the mitochondria. Quantitative RT-PCR and protein blotting indicated loss of function of OsNDUFA9 altered gene expression and protein accumulation associated with respiratory electron chain complex in the mitochondria. Moreover, transmission electron microscopic analysis showed that the mutant lacked obvious mitochondrial cristae structure in the mitochondria of endosperm cell. Our results demonstrate that the OsNDUFA9 subunit of complex I is essential for embryo development and starch synthesis in rice endosperm. [ABSTRACT FROM AUTHOR]

Recent observational studies showed that breast-conserving surgery (BCS) resulted in superior survival compared to mastectomy in breast cancer patients. This study compared the clinical outcomes of BCS and mastectomy using propensity score (PS) matching analysis, which had advantages over conventional methods in reducing bias. Nonmetastatic breast cancer patients who underwent BCS and mastectomy were matched 1:1 based on their PS. We used the Kaplan-Meier method and Cox-regression model to estimate the treatment effects. A total of 2,866 patients with a median follow-up time of 67 months were included in the original study population. Although the mastectomy cohort (N=1,219) had more advanced disease compared to the BCS cohort (N=1,647), LRFS was similar between the two groups (93.8% vs. 92.4%, P>0.05). BCS (vs. mastectomy) was associated with improved DFS (73.8% vs. 58.7%, P<0.01) and CSS (91% vs. 78.2%, P<0.01) in the original population. In the PS-matched population (N=1,668), clinicopathological features were equally distributed between the two cohorts. BCS (vs. mastectomy) was not associated with improved DFS (70.7% vs. 66.9%, P>0.05) or CSS (87.5% vs. 84.9%, P>0.05). We found that PS methods reduce bias when estimating treatment effects using observational data. BCS and mastectomy show equivalent outcomes in nonmetastatic breast cancer patients. [ABSTRACT FROM AUTHOR]

The occurrence of 15 perfluoroalkyl substances (PFASs) in water, sediments, and fish from Songhua River and Yalu River in Jilin Province, Northeast China, during their spring flood period were investigated for the first time. The short-chain perfluorobutanoic acid was the dominant PFAS in the water with the mean concentrations of 10 ng L−1 in Songhua River and 9.0 ng L−1 in Yalu River, and also dominant in sediments with the mean concentrations of 2.0 and 1.8 ng g−1 dry weight. Perfluorodecane sulfonate was the predominant compound in fish. The detected frequencies and concentrations of perfluorooctane sulfonate and perfluorooctanoic acid were very low in the water, sediments, and fish. Low detected frequencies and concentrations of long-chain PFASs led to relative low sediment-water partition coefficients and bioaccumulation factors. The concentration levels of PFASs in the two rivers were lower than those in other major rivers in China. [ABSTRACT FROM AUTHOR]

Supercritical water oxidation (SCWO) of penicillin (PCN) was investigated under different operating conditions. The chemical oxygen demand (COD) removal rate could reach 99.4% at 400 °C, 24 MPa, 1min and oxidation coefficient (OC) of 2. Experimental results showed that COD removal had no significant dependence on temperature and pressure variations. By contrast, COD removal could be significantly promoted with OC increasing from 0 to 2.0, but the effect was negligible as the OC further increased; similarly, longer residence time than a definite value seemed to contribute little to COD removal. Initial and deeper degradation pathways of penicillin were proposed based on the reactive force field (ReaxFF) molecular dynamics (MD) simulations. By tracing the evolution of intermediates, the migration routes of S and N during the SCWO process were obtained with H2S and NO2 produced as the corresponding products. Simulation results showed that SCW and oxidant not only accelerated the degradation by producing highly reactive radicals or molecules, but also participated in reactions by serving as H and O sources. Moreover, catalysis of water clusters in C-heteroatom bond cleavage was also observed. [ABSTRACT FROM AUTHOR]

Panax ginseng Meyer, commonly known as ginseng, is considered one of the most important herbs with pharmaceutical values due to the presence of ginsenosides and is cultivated for its highly valued root for medicinal purposes. Recently, it has been recognized that ginseng fruit contains high contents of triterpene such as ginsenoside Re as pharmaceutical compounds. However, it is unclear how carpel, the female reproductive tissue of flowers, is formed during the three-year-old growth before fruit is formed in ginseng plants. Here, we report P. ginseng carpel development at the cytological level, starting from the initial stage of ovule development to seed development. The carpel of P. ginseng is composed of two free stigmas, two free styles, and one epigynous bilocular ovary containing one ovule in each locule. Based on our cytological study, we propose that the female reproductive development in P. ginseng can be classified into seven stages: early phase of ovule development, megasporogenesis, megagametogenesis, pre-fertilization, fertilization, post-fertilization, and seed development. We also describe the correlation of the female and male gametophyte development and compare morphological differences in carpel development between ginseng and other higher plants. One unique feature for ginseng seed development is that it takes 40 days for the embryo to develop to the early torpedo stage and that the embryo is small relative to the seed size, which could be a feature of taxonomic importance. This study will provide an integral tool for the study of the reproductive development and breeding of P. ginseng. [ABSTRACT FROM AUTHOR]

We investigate solutions to nonlinear operator equations which are difficult to investigate with variational methods and obtain some abstract existence results by topology degree methods. These results apply to ordinary differential systems with impulsive effects satisfying nonlinear boundary value conditions, and we obtain some new results. [ABSTRACT FROM AUTHOR]

Background: MTBH, a novel hesperetin derivative, possesses in vivo hepatoprotective effects against carbon tetrachloride (CCl)-induced acute liver injury in Institute of Cancer Research (ICR) mice. Objectives: This study investigated the pharmacokinetics and tissue distribution of MTBH and its conjugated metabolites in rats after a single dose of MTBH. Methods: Male Sprague-Dawley (SD) rats were orally administered (25, 50, 100 mg/kg) or intravenously administered (25 mg/kg) MTBH and blood samples were withdrawn at specific times. Moreover, after a single oral dose of MTBH (200 mg/kg), tissues (heart, liver, spleen, lung, kidney, stomach, intestine, brain and muscle) were collected at scheduled time points. Results: The concentration of MTBH in plasma and tissues was assayed by HPLC before and after hydrolysis with β-glucuronidase or sulfatase. The glucuronides/sulfates were extensively present in the plasma, moreover, the free form was detectable in the plasma, but in a small amount equivalent to nearly 0.85-1.46 % of the amount of glucuronides/sulfates, the absolute bioavailability of MTBH was approximately 31.27 %. In tissues, the free form appeared in all tissues examined, with trace amount in brain and muscle, and considerable concentration in stomach and lung. Glucuronides/sulfates were the major forms in intestine, kidney and liver, whereas not detectable in heart, brain and muscle. The liver and intestine were found likely to accumulate MTBH at a high concentration among all tissues. Conclusions: The free form of MTBH was present in the circulation and all assayed organs, whereas its glucuronides/sulfates were the major forms in plasma and intestine, kidney and liver after a single dose. [ABSTRACT FROM AUTHOR]

Ephrin-A2, a member of the Eph/ephrin family, is associated with tumorigenesis and tumor progression. This study aimed to assess the diagnostic and prognostic value of both serum and tissue levels of Ephrin-A2 in prostate cancer (PCa) management. One hundred and forty-five frozen prostate tissues, 55 paraffin-embedded prostate tissues, 88 serum samples, and seven prostate cell lines (RWPE-1, LNCaP, LNCaP-LN3, PC-3, PC-3M, PC-3M-LN4, and DU145) were examined via quantitative reverse transcription-PCR (qRT-PCR), immunohistochemistry, enzyme-linked immunosorbent assay, and western blotting. Induced Ephrin-A2 messenger RNA (mRNA) or protein expression was detected in 8.6 % (5/58) benign prostatic hyperplasia (BPH), 59.8 % (52/87) PCa, and five prostate cancer cell lines. Ephrin-A2 immunostaining was present in 6.7 % (1/15) patients with BPHs and 62.5 % (25/40) clinically localized PCa. Accordingly, serum Ephrin-A2 was significantly higher in PCa patients compared to those in the BPH patients and controls ( P < 0.001). The expression of Ephrin-A2 was higher in tumor patients with an elevated Gleason score or T3-T4 staging. Ephrin-A2 expression was correlated with Ki-67 expression in PCa patients, both at the gene scale and protein level. Our data indicate that Ephrin-A2 is a potential diagnostic and prognostic biomarker and a promising molecular therapeutic target to attenuate prostate cancer progression. [ABSTRACT FROM AUTHOR]

Background and Objective: Henagliflozin, a selective inhibitor of the renal sodium glucose cotransporter-2, was developed for type 2 diabetes mellitus (T2DM). This study characterized single- and multiple-dose pharmacokinetics and pharmacodynamics of henagliflozin in Chinese patients with T2DM. Methods: Thirty T2DM patients were randomized in a 4:1 ratio to orally receive either henagliflozin 5, 10, 20 mg/day or placebo for 10 days, except on day 2 and day 3. Pharmacokinetic and pharmacodynamic profiles were measured on day 1 and day 10. Results: Henagliflozin exhibited dose-proportional plasma concentrations with a half-life ranging from 9.1 to 14 h. Steady-state plasma henagliflozin concentration was reached by day 7 in all active treatment groups. Henagliflozin decreased the 24-h mean plasma glucose by −0.3, −1.0 and −1.0 mmol/L with doses of 5, 10 and 20 mg on day 1, respectively. The corresponding values on day 10 were −0.8, −0.9 and −1.2 mmol/L. Twenty-four-hour urinary glucose excretion increased by 11, 65 and 82 times with doses of 5, 10 and 20 mg on day 1, respectively, with a similar trend on day 10. No treatment-related serious adverse events or discontinuations due to adverse events occurred. Conclusions: The observed pharmacokinetic and pharmacodynamic profiles of henagliflozin support a once-daily dosing regimen in Chinese T2DM patients. [ABSTRACT FROM AUTHOR]

Water availability for agricultural production may be significantly influenced by climate change. A decline in precipitation along with an increase in temperature will augment crop irrigation water requirement, especially during drought periods. Water footprint (WF) was provided to assess water resources utilization in the agricultural production process under climate variation. This paper analyzes the impact of climate change on WF of crop production at Lake Dianchi Basin, China, during 1981-2011. Results indicate that: (1) Crop evapotranspiration and irrigation water requirement of crop products presented an uptrend owing to the climate factors variation in the study period. (2) The total WF, mainly influenced by temperature and precipitation, experienced a steady upward tendency, exhibiting a trend of 50.42 m ton yr. WF showed a decreasing tendency, while WF showed the opposite, with an abrupt growth appeared in 2010 due to the extreme drought. (3) SPEI can be effectively used to identify and track regional drought events, which could result in the increase in WF. WF was positively correlated with the average SPEI, whereas WF showed the opposite. Nevertheless, water use efficiency and agricultural adaption management should be improved to cope with climate change. [ABSTRACT FROM AUTHOR]

Two commercial quantitative immunoassay platforms are currently available for the detection of hepatitis B surface antigen (HBsAg) within a wide range of concentrations: the Architect HBsAg assay and the Elecsys HBsAg II. However, there are limited data concerning their performance in patients who are positive for both HBsAg and anti-HBs antibodies. In the present study, 127 serum samples from Chinese patients with hepatitis B carrying both HBsAg and anti-HBs antibodies were analyzed. HBsAg levels measured in parallel using the Elecsys HBsAg II and Architect HBsAg assay were compared. There was a significant correlation between HBsAg levels measured by Elecsys HBsAg II and Architect HBsAg assay (correlation coefficient, r = 0.992, P < 0.05). Bland-Altman analysis indicated only minor discordance between the methods (mean difference between Elecsys HBsAg II and Architect HBsAg assay, −0.02 log IU/ml; 95 % confidence interval, −0.40-0.37 log IU/ml). In conclusion, the results of the quantitative Elecsys HBsAg II were highly correlated with those of the Architect HBsAg assay in patients carrying both HBsAg and anti-HBs antibodies, but differences were observed between the platforms in samples with low HBsAg levels. [ABSTRACT FROM AUTHOR]

Background and objective: JAK2 V617F mutation is a molecular marker for myeloproliferative neoplasms (MPNs). As there are no China Food and Drug Administration-approved assays for the detection of JAK2 V617F mutation in China, validation of the analytic performance of this assay is important for the clinical laboratory before its clinical implementation. We have established a method for detecting JAK2 V617F using tetra-primer amplification refractory mutation system-polymerase chain reaction (tetra-primer ARMS-PCR) combined with melting-curve analysis. Methods: A total of 202 blood samples and 20 bone marrow aspirates were obtained from MPNs patients at Huashan Hospital, Fudan University. The accuracy, precision, reproducibility, analytical sensitivity, lower limit of detection, analytical specificity, interfering substances, ruggedness, robustness, reportable range and reporting of this assay were validated. Results: There was a close agreement between the reference method (sequencing) and melting-curve analysis ( κ = 0.89). The precision was 100 % and the results of the assay were unaffected by lipoprotein (<27 mmol/L) or bilirubin (<450 µmol/L). The analytical sensitivity of the JAK2 mutation was 1.25 %. Conclusions: Tetra-primer amplification refractory mutation system-polymerase chain reaction (tetra-primer ARMS-PCR) combined with melting-curve analysis can be used in the clinical laboratory for detection of the JAK2 V617F mutation. [ABSTRACT FROM AUTHOR]

We developed a localized surface plasmon resonance (LSPR)-based label-free optical biosensor for detection of salbutamol (Sal). Hollow gold nanoparticles (HGNs) which deposited on transparent indium tin oxide (ITO) film coated glass was used to sensing platform. Antibody against Sal was immobilized on HGN surface to recognize the target Sal molecules. Thus, the change of LSPR peak was proportional to the concentration of Sal in the solution. The experimental results demonstrated that the LSPR immunosensor possessed a good sensitivity and a high selectivity for Sal. The detection range for Sal was from 0.05 to 0.8 μg/mL with a correlation coefficient of 0.996. The biosensor was applied for the detection for Sal in spiked animal feed and pork liver samples, and the recoveries were in the range of 97-105 %. Therefore, it is expected that this approach may offer a new method in designing label-free LSPR immunosensor for detection of small molecules. [ABSTRACT FROM AUTHOR]

The presence of JAK2 V617F is associated with an inherited JAK2 46/1 haplotype, a risk factor for myeloproliferative neoplasms (MPN) in Caucasian populations. Whether the JAK2 46/1 haplotype is also a risk factor in the Chinese population is unknown. We assessed for the JAK2 46/1 haplotype and JAK2 V617F mutation in 225 MPN patients and 226 controls using a tagged SNP rs12340895. The allele frequencies of the JAK2 46/1 haplotype were distinct among different subtypes of MPN patients. The allele frequency was significantly higher in polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) than that in controls, with PV patients having the highest allele frequency (0.58, P = 6.00E−15). The distribution of rs12340895 genotypes in the JAK2 V617F mutated MPN patients was significantly different from that in controls ( P = 1.67E−15). The percentage of GG genotype in controls was 2.2 %, but 31.0 % in JAK2 V617F-positive MPN patients. All the PV, ET, and PMF patients with the GG genotype also exhibited the V617F mutation. Compared to that of controls, the difference in genotype distribution in PV patients was the most significant ( P = 4.83E−21), followed by ET ( P = 2.07E−05) and PMF ( P = 1.99E−04). Our results suggest that the JAK2 46/1 haplotype is a risk factor for MPN in the Chinese population, and patients with GG genotype in rs12340895 locus are susceptible to JAK2 V617F mutation. [ABSTRACT FROM AUTHOR]

We aimed to determine the prevalence of the coexistence of HBsAg and anti-HBs and to analyze the clinical and virological features of infection, including amino acid (aa) patterns of the S gene and reverse transcriptase (RT) region in Chinese chronic hepatitis B (CHB) patients. Fifty-four (2.90%) CHB patients who were positive for both HBsAg and anti-HBs were tested, and sequences were obtained from 52 of them as well as 48 patients from a control group. S gene and RT region sequences were amplified and sequenced using in-house protocols. There was no significant difference between patients with and without anti-HBs with regard to age, gender, alanine aminotransferase level, and the proportion positive for HBeAg and HBcAb. The occurrence of genotype C (P = 0.001) and anti-HBeAb positivity (P = 0.027) was significantly higher in HBsAg+/anti-HBs+ individuals. In the S gene, the number of mutated residues in the HBsAg+/anti-HBs+ group was markedly higher than in control patients (1.88 versus 1.02 substitutions per 100 amino acids, P = 0.022). The amino acid exchange occurred mostly within the N-terminal region (2.15 versus 0.87 substitutions per 100 amino acids, P = 0.023) and the 'a' determinant (3.61 versus 1.56 substitutions per 100 amino acids, P = 0.049) in the two groups. In the RT region, the mean number of substitution per 100 aa showed a tendency to be significantly higher in HBsAg+/anti-HBs+ patients than in controls (2.34 versus 1.46, P = 0.040). This study showed a prevalence of coexistence of anti-HBs in HBsAg-positive patients and an increased frequency of genotype C and aa variability within both HBsAg and RT involving functionally important regions of those proteins. [ABSTRACT FROM AUTHOR]