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Abstract Background To compare the differences in long-term quality of life (QoL) between survivors of paediatric and adult patients with nasopharyngeal carcinoma (NPC) and assess the clinical factors that predict long-term QoL. Methods We enrolled 420 long-term NPC survivors who were alive for at least 8 years after treatment, including 195 paediatric and 225 adult patients diagnosed and treated with intensity-modulated radiotherapy (IMRT) at Sun Yat-sen University Cancer Centre (SYSUCC) between 2011 and 2015. Data on clinical factors and EORTC QLQ-C30 were collected from all participants. The QoL of paediatric and adult NPC survivors was compared. Results The paediatric group had significantly better outcomes in global health status (paediatric: 80.2 ± 12.7; adult: 77.2 ± 11.5; P = 0.027), physical function (paediatric: 98.5 ± 4.6; adult: 95.1 ± 7.0; P

AbstractBackground Decrease in estimated glomerular filtration rate (eGFR) during Tenofovir disoproxil fumarate (TDF) treatment remains a concern, and few patients experience partial recovery of eGFR. This study aimed to investigate the risk factors for eGFR recovery in patients with and without hypertriglyceridemia.Methods A total of 203 patients with chronic HBV infection were prospectively recruited and followed up for three years. Data were collected at baseline, first, second, and third years during TDF treatment.Results Most patients achieved normal ALT (80.0% vs. 82.5%) and undetectable HBV DNA (95.0% vs. 95.6%) in both groups (p > 0.05). For patients with hypertriglyceridemia, eGFR and cholesterol did not change significantly during the 3-year follow-up, while triglyceride (TG) decreased significantly in the first year and persisted at a lower level in the subsequent two years. For patients without hypertriglyceridemia, eGFR declined significantly in the first year of treatment, then gradually recovered during the subsequent two years, and eGFR was negatively correlated with TG at the four time points. Fifteen (15/183, 8.2%) patients without hypertriglyceridemia experienced eGFR partial recovery in the third year. Univariate and multivariate analyses showed that baseline eGFR

ABSTRACTAs a special class of stable atomic clusters, the superatom has become an exciting research topic in recent decades. They can mimic the chemistry and physics of individual atoms in the periodic table and find potential applications in a variety of fields. Traditional strategies for superatom design, however, have their own limitations. Herein, we review recent progress in the discovery of novel methodologies for superatom design, namely external-field regulated strategies (EFRS). We begin with a description of the basic concept of the superatom and the conventional electron-counting rules for superatom design, followed by a discussion of recent exploration about external-field regulated superatoms, where the oriented external electric field (OEEF), the ligand field, and the solvent field are presented. In the concluding section, we discuss the benefits and challenges of the EFRS together with some future research topics.

Abstract This study aimed to assess the correlation between serum albumin levels and coronary heart disease (CHD) risk in adults aged over 45 years. This cross-sectional study used the non-institutionalized US population from the National Health and Nutrition Examination Survey (NHANES 2011–2018) as the sample source. Multiple logistic regression was performed to evaluate the association between serum albumin levels and CHD risk. Smooth curve fitting was performed to explore potential nonlinear relationships. When nonlinear relationships were found, a recursive algorithm was used to calculate inflection points. Additionally, a piecewise logistic regression model was constructed. After adjusting for confounders, multiple logistic regression and smooth curve fitting indicated an inverse association between serum albumin levels and CHD risk [OR = 0.970, 95% CI = (0.948, 0.992)]. Subgroup analysis revealed that the negative correlation was statistically significant in the population of female patients, over 60 years, with hypertension, without diabetes. There was a correlation between serum albumin levels and CHD risk. Lower serum albumin levels were associated with a higher CHD risk.

Abstract Background Tuberculosis (TB) is one of the main infectious diseases that seriously threatens global health, while diagnostic delay (DD) and treatment dramatically threaten TB control. Methods Between 2005 and 2017 in Shandong, China, we enrolled pulmonary tuberculosis (PTB) patients with DD. DD trends were evaluated by Joinpoint regression, and associations between PTB patient characteristics and DD were estimated by univariate and multivariate logistic regression. The influence of DD duration on prognosis and sputum smear results were assessed by Spearman correlation coefficients. Results We identified 208,822 PTB cases with a median DD of 33 days (interquartile range (IQR) 18–63). The trend of PTB with DD declined significantly between 2009 and 2017 (annual percent change (APC): − 4.0%, P = 0.047, 2009–2013; APC: − 6.6%, P = 0.001, 2013–2017). Patients aged > 45 years old (adjusted odds ratio (aOR): 1.223, 95% confidence interval (CI) 1.189–1.257, 46–65 years; aOR: 1.306, 95% CI 1.267–1.346, > 65 years), farmers (aOR: 1.520, 95% CI 1.447–1.596), and those with a previous treatment history (aOR: 1.759, 95% CI 1.699–1.821) were prone to developing long DD (> 30 days, P

Abstract Background Drug-resistant tuberculosis (DR-TB), obesity, and malnutrition are growing public health problems in the world. However, little has discussed the impact of different BMI status on the emergence of TB drug resistance. We aimed to explore the drug-resistant profiles of DR-TB and its clinical predictors among underweight, overweight or obesity population. Methods 8957 newly diagnosed TB cases with drug susceptibility results and BMI data in Shandong China, from 2004 to 2019 were enrolled. Multivariable and univariable logistic regression models were applied to investigate the impact of BMI on different drug-resistance. Clinical predicators and drug-resistant profiles of DR-TB among obesity, underweight, normal TB group were also described. Results Among 8957 TB cases, 6417 (71.64%) were normal weight, 2121 (23.68%) were underweight, 373 (4.16%) were overweight, and 46 (0.51%) were obese. The proportion of drug resistance and co-morbidity among normal weight, underweight, overweight, obese TB groups were 18.86%/18.25%/20.38%/23.91% (DR-TB), 11.19%/11.74%/9.65%/17.39% (mono-resistant tuberculosis, MR-TB), 3.41%/3.06%/5.36%/0.00% (multidrug resistant tuberculosis, MDR-TB), 4.21%/3.39%/5.36%/6.52% (polydrug resistant tuberculosis, PDR-TB), 10.57%/8.44%/19.57%/23.91% (co-morbidity), respectively. Compared with normal weight group, underweight were associated with lower risk of streptomycin-related resistance (OR 0.844, 95% CI 0.726–0.982), but contributed to a higher risk of MR-TB (isoniazid) (odds ratio (OR) 1.347, 95% CI 1.049–1.730; adjusted OR (aOR) 1.31, 95% CI 1.017–1.686), P

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) disrupts the blood-testis barrier (BTB), resulting in alterations in spermatogenesis. However, whether BTB-related proteins (such as ZO-1, claudin11, N-cadherin, and CX43) are targeted by SARS-CoV-2 remains to be clarified. BTB is a physical barrier between the blood vessels and the seminiferous tubules of the animal testis, and it is one of the tightest blood-tissue barriers in the mammalian body. In this study, we investigated the effects of viral proteins, via ectopic expression of individual viral proteins, on BTB-related proteins, the secretion of immune factors, and the formation and degradation of autophagosomes in human primary Sertoli cells. Our study demonstrated that ectopic expression of viral E (envelope protein) and M (membrane protein) induced the expressions of ZO-1 and claudin11, promoted the formation of autophagosomes, and inhibited autophagy flux. S (spike protein) reduced the expression of ZO-1, N-cadherin, and CX43, induced the expression of claudin11, and inhibited the formation and degradation of autophagosomes. N (nucleocapsid protein) reduced the expression of ZO-1, claudin11, and N-cadherin. All the structural proteins (SPs) E, M, N, and S increased the expression of the FasL gene, and the E protein promoted the expression and secretion of FasL and TGF-β proteins and the expression of IL-1. Blockage of autophagy by specific inhibitors resulted in the suppression of BTB-related proteins by the SPs. Our results indicated that SARS-CoV-2 SPs (E, M, and S) regulate BTB-related proteins through autophagy.

Abstract Background Considering the high morbidity and mortality of lung cancer and the high incidence of pulmonary nodules, clearly distinguishing benign from malignant lung nodules at an early stage is of great significance. However, determining the kind of lung nodule which is more prone to lung cancer remains a problem worldwide. Methods A total of 480 patients with pulmonary nodule data were collected from Shandong, China. We assessed the clinical characteristics and computed tomography (CT) imaging features among pulmonary nodules in patients who had undergone video‐assisted thoracoscopic surgery (VATS) lobectomy from 2013 to 2018. Preliminary selection of features was based on a statistical analysis using SPSS. We used WEKA to assess the machine learning models using its multiple algorithms and selected the best decision tree model using its optimization algorithm. Results The combination of decision tree and logistics regression optimized the decision tree without affecting its AUC. The decision tree structure showed that lobulation was the most important feature, followed by spiculation, vessel convergence sign, nodule type, satellite nodule, nodule size and age of patient. Conclusions Our study shows that decision tree analyses can be applied to screen individuals for early lung cancer with CT. Our decision tree provides a new way to help clinicians establish a logical diagnosis by a stepwise progression method, but still needs to be validated for prospective trials in a larger patient population.

Objectives To investigate the independent and collective impact of alcohol drinking and tobacco smoking on the drug-resistance of newly diagnosed tuberculosis (TB).Design This was a retrospective cohort study.Setting Shandong, China.Participants Patients with newly diagnosed TB from 1 January 2004 to 31 December 2020 were collected. Exclusive criteria: retreated cases; extrapulmonary tuberculosis; without information on drug susceptibility testing results, smoking or drinking habits; bacteriological identification as non-tuberculous mycobacteria.Primary and secondary outcome measures Patients were classified into four groups including smokers only (G1), drinker only (G2), smoker +drinker (G3), non-smoker +non-drinker group (G0). We described the drug-resistant profiles, clinical factors and calculated the ORs of different drug-resistance among G1, G2, G3, compared with G0 through univariate and multivariate logistics regression models.Results Of the 7996 TB cases enrolled, the proportions of G1, G2, G3 and G0 were 8.25%, 3.89%, 16.46% and 71.40%, respectively. The rates of drug-resistant (DR)-TB, mono-resistant TB, multidrug resistant (MDR)-TB, polydrug resistant TB in G1, G2, G3 and G0 were 19.24%/16.4%/17.33%/19.08%, 11.52%/8.68%/10.94%/11.63%, 3.03%/2.57%/2.96%/3.66% and 4.70%/4.82%/3.34%/ 4.08%, respectively. G3 had a higher risk of MDR1: isoniazid +rifampin (adjusted OR (aOR)=1.91, 95% CI: 1.036 to 3.532), but had a lower risk of DR-TB (aOR=0.84, 95% CI: 0.71 to 0.99), rifampin-related resistance (aOR=0.68, 95% CI: 0.49 to 0.93), streptomycin-related resistance (aOR=0.82, 95% CI: 0.68 to 0.99), ethambutol-related resistance (aOR=0.57, 95% CI: 0.34 to 0.95), MDR3: isoniazid +rifampin+streptomycin (aOR=0.41, 95% CI: 0.19 to 0.85), any isoniazid +streptomycin resistance (aOR=0.85, 95% CI: 0.71 to 1.00). However, there were no significant differences between G1 and G0, G2 and G0 in all drug-resistant subtypes. Those patients with cavity had a higher risk of DR-TB among G3 (OR=1.35, 95% CI: 1.01 to 1.81).Conclusion Although we did not found an independent impact of alcohol drinking or tobacco smoking on TB drug-resistance, respectively, these two habits had a combined effect on TB drug-resistance.

Abnormal refraction and reflection refers to the phenomenon in which light does not follow its traditional laws of propagation and instead is subject to refraction and reflection at abnormal angles that satisfy a generalization of Snell’s law. Metasurfaces can realize this phenomenon through appropriate selection of materials and structural design, and they have a wide range of potential applications in the military, communications, scientific, and biomedical fields. This paper summarizes the current state of research on abnormal refractive and reflective metasurfaces and their application scenarios. It discusses types of abnormal refractive and reflective metasurfaces based on their tuning modes (active and passive), their applications in different wavelength bands, and their future development. The technical obstacles that arise with existing metasurface technology are summarized, and prospects for future development and applications of abnormal refractive and reflective metasurfaces are discussed.

Abstract Background To explore population aging and the epidemic trend of pulmonary tuberculosis (PTB) in the elderly, and provide a basis for the prevention and control of pulmonary tuberculosis among the elderly. Methods We collected clinical information of 239,707 newly active PTB patients in Shandong Province from 2005 to 2017. We analyzed and compared the clinical characteristics, reported incidence and temporal trend of PTB among the elderly group (≥60 years) and the non-elderly group (

Abstract Background Tuberculosis (TB) is one of the major infectious diseases that seriously endanger people’s health. In Shandong province, the relationship between the level of economic development and TB incidence has not been studied. This study aims to provide more research basis for the government to prevent and control TB by exploring the impact of different economic factors on TB incidence. Methods By constructing threshold regression model (TRM), we described the extent to which different economic factors contribute to TB registered incidence and differences in TB registered incidence among seventeen cities with different levels of economic development in Shandong province, China, during 2006–2017. Data were retrieved from the China Information System for Disease Control and Prevention. Results Per capita medical expenditure (regression coefficient, -0.0314462; SD, 0.0079305; P > |t|, 0.000) and per capita savings (regression coefficient, 0.0001924; SD, 0.0000566; P > |t|, 0.001) passed the significance test at the level of 1%.They are the two economic indicators that have the greatest impact on TB registered incidence. Through the threshold test, we selected the per capita savings as the threshold variable. In the three stages of per capita savings (33,835.5391 CNY), rural per capita income always has a significant negative impact on the TB registered incidence (The regression coefficients are − 0.0015682, − 0.0028132 and − 0.0022253 respectively. P is 0.007,0.000 and 0.000 respectively.).In cities with good economies, TB registered incidence was 38.30% in 2006 and dropped to 25.10% by 2017. In cities with moderate economies, TB registered incidence peaked in 2008 at 43.10% and dropped to 27.1% by 2017.In poorer cities, TB registered incidence peaked in 2008 at 56.30% and dropped to 28.9% in 2017. Conclusion We found that per capita savings and per capita medical expenditure are most closely related to the TB incidence. Therefore, relevant departments should formulate a more complete medical system and medical insurance policy to effectively solve the problem of “difficult and expensive medical treatment”. In order to further reduce the TB incidence, in addition to timely and accurate diagnosis and treatment, it is more important for governments to increase investment in medicine and health care.

Background: Drug-resistant tuberculosis (DR-TB), diabetes and exposure to air pollution are thought to be important threat to human health, but no studies have explored the effects of ambient air pollutants on DR-TB when adjusting diabetes status so far. Methods: We performed a study among 3759 newly diagnosed TB cases with drug-susceptibility testing results, diabetes status, and individual air pollution data in Shandong from 2015 to 2019. Generalized linear mixed models (GLMM) including three models (Model 1: without covariates, Model 2: adjusted by diabetes status only, Model 3: with all covariates) were applied. Results: Of 3759 TB patients enrolled, 716 (19.05%) were DR-TB, and 333 (8.86%) had diabetes. High exposure to O3 was associated with an increased risk of RFP-resistance (Model 2 or 3: odds ratio (OR) = 1.008, 95% confidence intervals (CI): 1.002–1.014), ethambutol-resistance (Model 3: OR = 1.015, 95%CI: 1.004–1.027) and any rifampicin+streptomycin resistance (Model 1,2,3: OR = 1.01, 95%CI: 1.002–1.018) at 90 days. In contrast, NO2 was associated with a reduced risk of DR-TB (Model 3: OR = 0.99, 95%CI: 0.981–0.999) and multidrug-resistant TB (MDR-TB) (Model 3: OR = 0.977, 95%CI: 0.96–0.994) at 360 days. Additionally, SO2 (Model 1, 2, 3: OR = 0.987, 95%CI: 0.977–0.998) showed a protective effect on MDR-TB at 90 days. PM2.5 (90 days, Model 2: OR = 0.991, 95%CI: 0.983–0.999), PM10 (360 days, Model 2: OR = 0.992, 95%CI: 0.985–0.999) had protective effects on any RFP+SM resistance. Conclusions: O3 contributed to an elevated risk of TB resistance but PM2.5, PM10, SO2, NO2 showed an inverse effect. Air pollutants may affect the development of drug resistance among TB cases by adjusting the status of diabetes.

Background: Coronavirus disease 2019 (COVID-19) and tuberculosis (TB) are two major infectious diseases posing significant public health threats, and their coinfection (aptly abbreviated COVID-TB) makes the situation worse. This study aimed to investigate the clinical features and prognosis of COVID-TB cases.Methods: The PubMed, Embase, Cochrane, CNKI, and Wanfang databases were searched for relevant studies published through December 18, 2020. An overview of COVID-TB case reports/case series was prepared that described their clinical characteristics and differences between survivors and deceased patients. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) for death or severe COVID-19 were calculated. The quality of outcomes was assessed using GRADEpro.Results: Thirty-six studies were included. Of 89 COVID-TB patients, 19 (23.46%) died, and 72 (80.90%) were male. The median age of non-survivors (53.95 ± 19.78 years) was greater than that of survivors (37.76 ± 15.54 years) (p < 0.001). Non-survivors were more likely to have hypertension (47.06 vs. 17.95%) or symptoms of dyspnea (72.73% vs. 30%) or bilateral lesions (73.68 vs. 47.14%), infiltrates (57.89 vs. 24.29%), tree in bud (10.53% vs. 0%), or a higher leucocyte count (12.9 [10.5–16.73] vs. 8.015 [4.8–8.97] × 109/L) than survivors (p < 0.05). In terms of treatment, 88.52% received anti-TB therapy, 50.82% received antibiotics, 22.95% received antiviral therapy, 26.23% received hydroxychloroquine, and 11.48% received corticosteroids. The pooled ORs of death or severe disease in the COVID-TB group and the non-TB group were 2.21 (95% CI: 1.80, 2.70) and 2.77 (95% CI: 1.33, 5.74) (P < 0.01), respectively.Conclusion: In summary, there appear to be some predictors of worse prognosis among COVID-TB cases. A moderate level of evidence suggests that COVID-TB patients are more likely to suffer severe disease or death than COVID-19 patients. Finally, routine screening for TB may be recommended among suspected or confirmed cases of COVID-19 in countries with high TB burden.

Objective This study was designed to identify the risk factors for drug-resistant tuberculosis (DR-TB) and the association between comorbidity and drug resistance among retreated pulmonary tuberculosis (PTB).Design A retrospective study was conducted among all the 36 monitoring sites in Shandong, China, over a 16-year period. Baseline characteristics were collected from the TB Surveillance System. Categorical variables were compared by Fisher’s exact or Pearson’s χ2 test. The risk factors for drug resistance were identified using univariable analysis and multivariable logistic models. The influence of comorbidity on different types of drug resistance was evaluated by performing multivariable logistic models with the covariates adjusted by age, sex, body mass index, drinking/smoking history and cavity.Results A total of 10 975 patients with PTB were recorded during 2004–2019, and of these 1924 retreated PTB were finally included. Among retreated PTB, 26.2% were DR-TB and 12.5% had comorbidity. Smoking (adjusted OR (aOR): 1.69, 95% CI 1.19 to 2.39), cavity (aOR: 1.55, 95% CI 1.22 to 1.97) and comorbidity (aOR: 1.44, 95% CI 1.02 to 2.02) were risk factors for DR-TB. Of 504 DR-TB, 9.5% had diabetes mellitus, followed by hypertension (2.0%) and chronic obstructive pulmonary disease (1.8%). Patients with retreated PTB with comorbidity were more likely to be older, have more bad habits (smoking, alcohol abuse) and have clinical symptoms (expectoration, haemoptysis, weight loss). Comorbidity was significantly associated with DR-TB (aOR: 1.44, 95% CI 1.02 to 2.02), overall rifampin resistance (aOR: 2.17, 95% CI 1.41 to 3.36), overall streptomycin resistance (aOR: 1.51, 95% CI 1.00 to 2.27) and multidrug resistance (aOR: 1.96, 95% CI 1.17 to 3.27) compared with pan-susceptible patients (p

Solubilized particulate organic matter (POM) rather than dissolved organic matter (DOM) has been speculated to be the major carbon and energy sources for heterotrophic prokaryotes in the ocean. However, the direct evidence is still lack. Here we characterized microbial transport proteins of POM collected from both euphotic (75 m, deep chlorophyll maximum DCM, and 100 m) and upper-twilight (200 m and 500 m) zones in three contrasting environments in the northwest Pacific Ocean using a metaproteomic approach. The proportion of transport proteins was relatively high at the bottom of the euphotic zone (200 m), indicating that this layer was the most active area of microbe-driven POM remineralization in the water column. In the upper-twilight zone, the predicted substrates of the identified transporters indicated that amino acids, carbohydrates, taurine, inorganic nutrients, urea, biopolymers, and cobalamin were essential substrates for the microbial community. SAR11, Rhodobacterales, Alteromonadales, and Enterobacteriales were the key contributors with the highest expression of transporters. Interestingly, both the taxonomy and function of the microbial communities varied among water layers and sites with different environments; however, the distribution of transporter types and their relevant organic substrates were similar among samples, suggesting that microbial communities took up similar compounds and were functionally redundant in organic matter utilization throughout the water column. The similar vertical distribution of transport proteins from the euphotic zone to the upper twilight zone among the contrasting environments indicated that solubilized POM rather than DOM was the preferable carbon and energy sources for the microbial communities.

Regulatory T cells (Tregs) are essential for the maintenance of gut homeostasis by suppressing conventional CD4+ helper T cells (Tconvs) that are activated by microbial antigens. Although thymus is the major source of the peripheral Tregs, peripheral conversion from Tconvs to Tregs have also been shown to occur under various experimental conditions. It remains less clear about the frequency of lineage conversion from Tconvs to Tregs in naïve animals. Here we used a newly established reporter system to track a group of post expansion Tregs (eTregs), which exhibited a stronger suppressive ability than the non-lineage marked Tregs. Notably, microbial antigens are the primary driver for the formation of eTregs. TCR repertoire analysis of Peyer's patch T cells revealed that eTregs are clonally related to Tconvs, but not to the non-lineage tracked Tregs. Adoptive transfer of Tconvs into lymphopenic hosts demonstrated a conversion from Tconvs to eTregs. Thus, our lineage tracking method was able to capture the lineage conversion from microbial activated effector T cells to Tregs in naïve animals. This study suggests that a fraction of clonally activated T cells from the natural T cell repertoire exhibits lineage conversion to Tregs in response to commensal microbes under homeostatic conditions.

Abstract Background In Arabidopsis, the tapetum and microsporocytes are critical for pollen formation. Previous studies have shown that ARF17 is expressed in microsporocytes and tetrads and directly regulates tetrad wall synthesis for pollen formation. ARF17 is the direct target of miR160, and promoterARF17::5mARF17 (5mARF17/WT) transgenic plants, which have five silent mutations within the miR160-complementary domain, are sterile. Results Here, we found that ARF17 is also expressed in the tapetum, which was defective in arf17 mutants. Compared with arf17 mutants, 5mARF17/WT plants had abnormal tapetal cells and tetrads but were less vacuolated in the tapetum. Immunocytochemical assays showed that the ARF17 protein over-accumulated in tapetum, microsporocytes and tetrads of 5mARF17/WT plants at early anther stages, but its expression pattern was not affected during anther development. 5mARF17 driven by its native promoter did not rescue the arf17 male-sterile phenotype. The expression of 5mARF17 driven by the tapetum-specific promoter A9 led to a defective tapetum and male sterility in transgenic plants. These results suggest that the overexpression of ARF17 in the tapetum and microsporocytes of 5mARF17/WT plants leads to male sterility. Microarray data revealed that an abundance of genes involved in transcription and translation are ectopically expressed in 5mARF17/WT plants. Conclusions Our work shows that ARF17 plays an essential role in anther development and pollen formation, and ARF17 expression under miR160 regulation is critical for its function during anther development.

Phosphomannose isomerase (PMI) encoding gene manA is a desirable selective marker in transgenic research. Understanding of its expression patterns in transgenic plant and establishing highly sensitive detection method based on immunoassay have great impacts on the application of PMI. In this study, PMI-specific monoclonal antibodies were generated using recombinant protein as immunogen, and could be used in Western blot to detect as little as 0.5 ng His-tagged PMI protein or rice expressed PMI protein in sample accounted for 0.4% of single rice grain (about 0.08 mg). PMI protein driven by CaMV-35S promoter was detected in dozens of tested tissues, including root, stem, leaf, panicle, and seed at all developmental stages during rice growing, and PMI protein accounted for about 0.036% of total protein in the leaves at seedling stage. The established method potentially can be used to monitor PMI protein in rice grains.

The study was aimed to determine whether treatment with oat oligopeptides (OOPs) could modulate hyperglycemia related to type 2 diabetes mellitus (T2DM) in Sprague⁻Dawley (SD) rats. Diabetic SD rats modeling by a joint effect of high-calorie diet for 45 days and twice intraperitoneal injection of 30 mg/kg streptozotocin at one-week interval were observed with or without OOPs administration (0.25, 0.50, 1.00, and 2.00 g/kg Body Weight) for 12 weeks. Fasting blood glucose (FBG), oral glucose test tolerance (OGTT), serum insulin, level of antioxidant, and hepatic enzymes were measured. In addition, frequency of micturition was recorded in this study for the first time. It was observed that the administration of OOPs (2.00 g/kg Body Weight) resulted in a significant decrease (p < 0.05) in FBG since 6th week and a significant decrease (p < 0.05) in the OGTT-AUC on 6th and 10th week. In addition, the administration of OOPs (2.00 g/kg Body Weight) reduced HOMA-IR index and 24-h urine volume significantly (p < 0.05) whereas increased SOD activity significantly (p < 0.05). These results suggested that OOPs may have a hypoglycemic effect in diabetic rats.

Carbonatite hosts the most important rare earth resources in the world, but the precise timing, ore-forming history, and mechanism of rare earth mineralization in carbonatite systems are still in debate. Here, we report a rare corona texture of monazite-allanite-fluorapatite from the Huangjiagou carbonatite in the Lesser Qinling of central China, and demonstrate that the U-Th-Pb dating, trace elements, and Sr-Nd isotopes of these minerals in the corona are useful tools to unravel multiple-stage events for rare earth element (REE) mineralization and mobilization. The first mineralization event took place at ca. 219 Ma as revealed by the monazite U-Pb age, the same as regional carbonatite forming ages, but the Th-Pb age has been disturbed, which shows a negative correlation with Th contents. The second mineralization event occurred at ca. 128 Ma, as revealed by in situ U-Pb dating of allanite, coeval with the intrusions of neighboring I-type granite. The initial Sr-Nd isotope ratios of allanite show a downtrend from the center to the rim of monazite-allanite-apatite coronas to approach the ratios of neighboring granite, indicating an increasing effect by the metasomatism of magmatic-hydrothermal fluids during the growth of these REE-mineral coronas. Therefore, a two-episode REE mineralization was recognized with the replacement of ca. 219 Ma monazite by ca. 128 Ma allanite-apatite coronas on the function of magmatichydrothermal fluid metasomatism, and this process accompanies the disturbance of Th/Pb geochronology in monazite. Allanite as the product of monazite dissolution can represent the later-stage REE mineralization tracing the REE reworking processes under the hydrothermal conditions in carbonatite systems. Our study highlights the implication of monazite-allanite-fluorapatite coronas on the REE remobilization and mineralization in carbonatite systems. [ABSTRACT FROM AUTHOR]

The present study was designed to investigate the role of circulating miRNA-21 (miR-21) in vascular restenosis of lower extremity arterial occlusive disease (LEAOD) patients after interventional therapy. A total of 412 LEAOD patients were enrolled randomly in the present study. According to computed tomography angiography (CTA) and ankle-brachial index (ABI), patients were assigned into the restenosis group and the non-restenosis group. miR-21 expression was detected with quantitative real-time PCR (qRT-PCR) before and after patients underwent interventional therapy. A follow-up period of 6 months was achieved. A receiver operating characteristic (ROC) curve was drawn and the area under the curve (AUC) was calculated to assess the predictive value of miR-21 in vascular restenosis. Patients were older in the restenosis group than in the non-restenosis group. The percentages of patients with diabetes and hypertension were higher in the restenosis group than in the non-restenosis group, and the Fontaine stage exhibited a significant difference between the two groups. miR-21 expression was higher in the restenosis group than in the non-restenosis group. miR-21 expression level was related to age, diabetes and hypertension in the restenosis group. Using miR-21 to predict vascular restenosis yielded an AUC of 0.938 (95% confidence interval (CI): 0.898–0.977), with Youden index of 0.817, sensitivity of 83.5% and specificity of 98.2%. Logistic regression analysis revealed that diabetes and miR-21 expression were the major risk factors for vascular restenosis of LEAOD. miR-21 can be used as a predictive indicator for vascular restenosis of LEAOD after interventional therapy. [ABSTRACT FROM AUTHOR]

The miR-17-92 cluster regulates a broad spectrum of biological processes of T cell immunity. This cluster was found to facilitate T cell proliferation, enhance antitumor activities and promote T cell-dependent antibody responses. However, little is known about the role of this miRNA cluster in the development of autoimmune diseases. Multiple sclerosis is a neuro-destructive autoimmune disease caused by the pathogenicity of TH17 cells, whose differentiation is tightly controlled by a variety of transcriptional and post-transcriptional regulators. Our study unveils the critical role of miR-17-92 in TH17 differentiation: T cell-specific miR-17-92 deficiency reduced TH17 differentiation and ameliorated experimental autoimmune encephalomyelitis (EAE) symptoms. We demonstrated that miR-17 and miR-19b are the two miRNAs in this cluster responsible for promoting TH17 responses. MiR-19b represses the expression of Phosphatase and Tensin Homology (PTEN), thereby augmenting the PI3K-AKT-mTOR axis essential for proper TH17 differentiation. Meanwhile, miR-17 enhances TH17 polarization by inhibiting a novel target, Ikaros Family Zinc Finger 4 (IKZF4). By establishing the miR-17-92 cluster as a key driver of TH17 responses, our data identify this miRNA cluster as a potential therapeutic target for the clinical intervention of multiple sclerosis. [ABSTRACT FROM AUTHOR]

Comamonas sp. strain CNB-1 can utilize 4-chloronitrobenzene (4CNB) as sole carbon and nitrogen source for growth. Previous studies were focused on 4CNB degradative pathway and have showed thatCNB-1 contained a plasmid pCNB1 harboring the genes (cnbABCaCbDEFGH, cnbZ) for the enzymes involving in 4CNB degradation, but only three gene products (CnbCa, CnbCb, and CnbZ) were identified in CNB-1 cells. Comamonas strain CNB-2 that lost pCNB1 was not able to grow on 4CNB. In this study, physiological adaptation to 4CNB by CNB-1 was investigated with proteomic and molecular tools. Comparative proteomes of strains CNB-1 and CNB-2 grown on 4CNB and/or succinate revealed that adaptation to 4CNB by CNB-1 included specific degradative pathway and general physiological responses: (1) Seven gene products (CnbA, CnbCa,CnbCb, CnbD,CnbE,CnbF, andCnbZ) for 4CNB degradation were identified in 4CNB-grown cells, and they were constitutively synthesized in CNB-1. Two genes cnbE and cnbF were cloned and simultaneously expressed in E. coli. The CnbE and CnbF together catalyzed the conversion of 2-oxohex-4-ene-5- chloro-1,6-dioate into 2-oxo-4-hydroxy-5-chloro-valeric acid; (2) Enzymes involving in glycolysis, tricarboxylic acid cycle, and synthesis of glutamate increased their abundances in 4CNB-grown cells. [ABSTRACT FROM AUTHOR]

Myocardial ischaemia is associated with the generation of lipid peroxidation products such as HNE (4-hydroxy-trans-2-nonenal); however, the processes that predispose the ischaemic heart to toxicity by HNE and related species are not well understood. In the present study, we examined HNE metabolism in isolated aerobic and ischaemic rat hearts. In aerobic hearts, the reagent [3H]HNE was glutathiolated, oxidized to [3H]4-hydroxynonenoic acid, and reduced to [3H]1,4-dihydroxynonene. In ischaemic hearts, [3H]4-hydroxynonenoic acid formation was inhibited and higher levels of [3H]1,4-dihydroxynonene and [3H]GS-HNE (glutathione conjugate of HNE) were generated. Metabolism of [3H]HNE to [3H]4-hydroxynonenoic acid was restored upon reperfusion. Reperfused hearts were more efficient at metabolizing HNE than non-ischaemic hearts. Ischaemia increased the myocardial levels of endogenous HNE and 1,4-dihydroxynonene, but not 4-hydroxynonenoic acid. Isolated cardiac mitochondria metabolized [3H]HNE primarily to [3H]4-hydroxynonenoic acid and minimally to [3H]1,4-dihydroxynonene and [3H]GS-HNE. Moreover, [3H]4-hydroxynonenoic acid was extruded from mitochondria, whereas other [3H]HNE metabolites were retained in the matrix. Mitochondria isolated from ischaemic hearts were found to contain 2-fold higher levels of protein-bound HNE than the cytosol, as well as increased [3H]GS-HNE and [3H]1,4-dihydroxynonene, but not [3H]4-hydroxynonenoic acid. Mitochondrial HNE oxidation was inhibited at an NAD+/NADH ratio of 0.4 (equivalent to the ischaemic heart) and restored at an NAD+/NADH ratio of 8.6 (equivalent to the reperfused heart). These results suggest that HNE metabolism is inhibited during myocardial ischaemia owing to NAD+ depletion. This decrease in mitochondrial metabolism of lipid peroxidation products and the inability of the mitochondria to extrude HNE metabolites could contribute to myocardial ischaemia/reperfusion injury. [ABSTRACT FROM AUTHOR]

In a recent paper we proved that for certain class of perturbations of the hyperbolic equation u t = f ( u) u x , there exist changes of coordinate, called quasi-Miura transformations, that reduce the perturbed equations to the unperturbed one. We prove in the present paper that if in addition the perturbed equations possess Hamiltonian structures of certain type, the same quasi-Miura transformations also reduce the Hamiltonian structures to their leading terms. By applying this result, we obtain a criterion of the existence of Hamiltonian structures for a class of scalar evolutionary PDEs and an algorithm to find out the Hamiltonian structures. [ABSTRACT FROM AUTHOR]

The activity of the voltage-sensitive K+ (Kv) channels varies as a function of the intracellular redox state and metabolism, and several Kv channels act as oxygen sensors. However, the mechanisms underlying the metabolic and redox regulation of these channels remain unclear. In this study we investigated the regulation of Kv channels by pyridine nucleotides. Heterologous expression of Kva 1.5 in COS-7 cells led to the appearance of noninactivating currents. Inclusion of 0.1-1 mM NAD+ or 0.03-0.5 mM NADP+ in the internal solution of the patch pipette did not affect Kv currents. However, 0.5 and 1 mM NAD+ and 0.1 and 0.5 mM NADP+ prevented inactivation of Kv currents in cells transfected with Kvα1.5 and Kvβ1.3 and shifted the voltage dependence of activation to depolarized potentials. The Kvβ-dependent inactivation of Kvα currents was also decreased by internal pipette perfusion of the cell with 1 mM NAD+. The Kvα1.5-Kvβ1.3 currents were unaffected by the internal application of 0.1 mM NADPH or 0.1 or 1 mM NADH. Excised inside-out patches from cells expressing Kvα1.5-Kvβ1.3 showed transient single-channel activity. The mean open time and the open probability of these currents were increased by the inclusion of 1 mM NAD+ in the perfusate. These results suggest that NAD(P) + prevents Kvβ-mediated inactivation of Kv currents and provide a novel mechanism by which pyridine nucleotides could regulate specific K+ currents as a function of the cellular redox state [NAD(P)H-to-NAD(P)+ ratio]. [ABSTRACT FROM AUTHOR]

Sinking particles are a critical conduit for the transport of surface microbes to the ocean's interior. Vertical connectivity of phylogenetic composition has been shown; however, the functional vertical connectivity of microbial communities has not yet been explored in detail. We investigated protein and taxa profiles of both free-living and particle-attached microbial communities from the surface to 3000 m depth using a combined metaproteomic and 16S rRNA amplicon sequencing approach. A clear compositional and functional vertical connectivity of microbial communities was observed throughout the water column with Oceanospirillales, Alteromonadales, and Rhodobacterales as key taxa. The surface-derived particle-associated microbes increased the expression of proteins involved in basic metabolism, organic matter processing, and environmental stress response in deep waters. This study highlights the functional vertical connectivity between surface and deep-sea microbial communities via sinking particles and reveals that a considerable proportion of the deep-sea microbes might originate from surface waters and have a major impact on the biogeochemical cycles in the deep sea. [ABSTRACT FROM AUTHOR]

The article presents a research that studied the response by "Comamonas" sp. strain CNB-1 at proteomic and genetic levels to arsenate stress. The research cultured CNB-1 cells with and without arsenate to explore the proteins responding to arsenate stress. It also carried out differential proteomics by using two-dimensional PAGE (2-DE) and MALDI-TOF MS. The research found out that 23 proteins were responsive specifically to arsenate and 31 differential 2-DE spots were identified based on image analysis.