Reactions dynamics for X + H2 insertion reactions (X = C(1D), N(2D), O(1D), S(1D)) with Cayley propagator ring-polymer molecular dynamics.

In this work, rate coefficients of four prototypical insertion reactions, X + H2 → H + XH (X = C(1D), N(2D), O(1D), S(1D)), and associated isotope reactions are calculated based on ring polymer molecular dynamics (RPMD) with Cayley propagator (Cayley-RPMD). The associated kinetic isotope effects are systematically studied too. The Cayley propagator used in this work increases the stability of numerical integration in RPMD calculations and also supports a larger evolution time interval, allowing us to reach both high accuracy and efficiency. So, our results do not only provide chemical kinetic data for the title reactions in an extended temperature range but also consist of experimental results, standard RPMD, and other theoretical methods. The results in this work also reflect that Cayley-RPMD has strong consistency and high reliability in its investigations of chemical dynamics for insertion reactions.

Penehyclidine hydrochloride alleviates lung ischemia-reperfusion injury by inhibiting pyroptosis.

OBJECTIVE: The aim of this research was to examine how penehyclidine hydrochloride (PHC) impacts the occurrence of pyroptosis in lung tissue cells within a rat model of lung ischemia-reperfusion injury. METHODS: Twenty-four Sprague Dawley (SD) rats, weighing 250 g to 270 g, were randomly distributed into three distinct groups as outlined below: a sham operation group (S group), a control group (C group), and a test group (PHC group). Rats in the PHC group received a preliminary intravenous injection of PHC at a dose of 3 mg/kg. At the conclusion of the experiment, lung tissue and blood samples were collected and properly stored for subsequent analysis. The levels of malondialdehyde, superoxide dismutase, and myeloperoxidase in the lung tissue, as well as IL-18 and IL-1ß in the blood serum, were assessed using an Elisa kit. Pyroptosis-related proteins, including Caspase1 p20, GSDMD-N, and NLRP3, were detected through the western blot method. Additionally, the dry-to-wet ratio (D/W) of the lung tissue and the findings from the blood gas analysis were also documented. RESULTS: In contrast to the control group, the PHC group showed enhancements in oxygenation metrics, reductions in oxidative stress and inflammatory reactions, and a decrease in lung injury. Additionally, the PHC group exhibited lowered levels of pyroptosis-associated proteins, including the N-terminal segment of gasdermin D (GSDMD-N), caspase-1p20, and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3). CONCLUSION: Pre-administration of PHC has the potential to mitigate lung ischemia-reperfusion injuries by suppressing the pyroptosis of lung tissue cells, diminishing inflammatory reactions, and enhancing lung function. The primary mechanism behind anti-pyroptotic effect of PHC appears to involve the inhibition of oxidative stress.

Early Guideline-Directed Medical Therapy and in-Hospital Major Bleeding Risk in ST-Elevation Myocardial Infarction Patients Treated with Percutaneous Coronary Intervention: Findings from the CCC-ACS Project.

PURPOSE: Previous reports demonstrated a bleeding avoidance potential of angiotensin converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) and ß-blocker. It remains unclear whether early guideline-directed medical therapy [GDMT, i.e., the combined use of ß-blocker, angiotensin converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) and statin] confers protection against bleeding in the setting of high-intensity antithrombotic therapy. METHODS: We assessed associations between the use of early (within the first 24 h) GDMT and in-hospital major bleeds, ischemic events and mortality among ST-elevation myocardial infarction (STEMI) patients treated with percutaneous coronary intervention (PCI) in the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome project. RESULTS: Among 34,538 STEMI patients without contra-indications to GDMT and eligible for analysis, 35.5% received early GDMT. In a 1-to-2 propensity-score matched cohort, compared with non-early GDMT, early GDMT was associated with a 25% reduction in major bleeds [odds ratio (OR) 0.75, 95% confidence interval (CI) 0.60-0.94], with parallel reductions in ischemic events (OR 0.60, 95%CI 0.45-0.78) and in-hospital mortality (OR 0.43, 95%CI 0.31-0.61). Early GDMT-associated reduction in major bleeds was generally consistently observed across different major bleeding definitions and in sensitivity analyses. Additionally, no significant interaction was observed in subgroup analyses. CONCLUSION: In a large nationwide registry, early initiation of GDMT was associated with reduced risk for in-hospital major bleeds in STEMI patients treated with PCI. To improve the outcome of STEMI, further effort should be made to reinforce the early use of GDMT in this patient population.

Effect of sleep deprivation by MMP-WM on rat neurological function and Tau protein in hippocampus.

An in-depth understanding of the pathogenesis and mechanisms of sleep disorders is important for finding reliable treatments and interventions in the future. This study aims to explore the effect of sleep deprivation by modified multiple platform-water maze (MMP-WM) on rat neurological function and Tau protein in the hippocampus, as well as the intervention effect of remimazolam. First, 40 Sprague Dawley (SD) rats were divided into a control group (no treatment), a Rem group (remimazolam), an MMP-WM group (sleep deprivation model in rats established by MMP-WM), and a combined group (MMP-WM + remimazolam). Five rats were randomly selected from each group for behavior tests at 1 d and 7 d of drug administration or sleep deprivation for Morris water maze and open field test. After that, the rats were executed, the hippocampus was isolated for Nissl staining, and the protein expression of phosphorylated Tau (p-Tau) in the CA1 region of the hippocampus was measured by immunohistochemistry. At 1 d, the status in the MMP-WM group was more similar to that in the control group The MMP-WM group showed sparsely arranged hippocampal CA1 neurons, reduced number of Nissl bodies, prolonged escape latency, decreased number of platform crossings and percentage of activity time in the central region, substantially increased p-Tau expression. In contrast, the combined group showed significant improvement in nerve injury, behavior test results, p-Tau at 7 d compared with the MMP-WM group and the same group at 1 d. In addition, detection of brain-derived neurotrophic factor (BDNF) and neurotransmitter levels in the cerebrospinal fluid also showed improved neurologic function in the combined group. These results confirm tha MMP-WM was effective in the establishment of sleep deprivation rat model that accurately reflects the pathological manifestations of sleep disorders in human, and the use of remimazolam effectively reversed the pathological damage in sleep-deprived rats.

Reaction dynamics for the Cl(2P) + XCl → XCl + Cl(2P) (X = H, D, Mu) reaction on a high-fidelity ground state potential energy surface.

In this work, the dynamics of a prototypical heavy-light-heavy abstract reaction, Cl(2P) + HCl → HCl + Cl(2P), is investigated both by constructing a new potential energy surface (PES) and by rate coefficient calculations. Both the permutation invariant polynomial neural network method and the embedded atom neural network (EANN) method, based on ab initio MRCI-F12+Q/AVTZ level points, are used for obtaining globally accurate full-dimensional ground state PES, with the corresponding total root mean square error being only 0.043 and 0.056 kcal/mol, respectively. In addition, this is also the first application of the EANN in a gas-phase bimolecular reaction. The saddle point of this reaction system is confirmed to be nonlinear. In comparison with both the energetics and rate coefficients obtained on both PESs, we find that the EANN is reliable in dynamic calculations. A full-dimensional approximate quantum mechanical method, ring-polymer molecular dynamics with a Cayley propagator, is employed to obtain the thermal rate coefficients and kinetic isotopic effects of the title reaction Cl(2P) + XCl→ XCl + Cl(2P) (H, D, Mu) on both new PESs, and the kinetic isotope effect (KIE) is also obtained. The rate coefficients reproduce the experimental results at high temperatures perfectly but with moderate accuracy at lower temperatures, but the KIE is with high accuracy. The similar kinetic behavior is supported by quantum dynamics using wave packet calculations as well.

Genetic basis and adaptive implications of temperature-dependent and temperature-independent effects of drought on chickpea reproductive phenology.

Water deficit often hastens flowering of pulses partially because droughted plants are hotter. Separating temperature-independent and temperature-dependent effects of drought is important to understand, model, and manipulate phenology. We define a new trait, drought effect on phenology (DEP), as the difference in flowering time between irrigated and rainfed crops, and use FST genome scanning to probe for genomic regions under selection for this trait in chickpea (Cicer arietinum). Owing to the negligible variation in daylength in our dataset, variation in phenology with sowing date was attributed to temperature and water; hence, genomic regions overlapping for early- and late-sown crops would associate with temperature-independent effects and non-overlapping genomic regions would associate with temperature-dependent effects. Thermal-time to flowering was shortened with increasing water stress, as quantified with carbon isotope composition. Genomic regions on chromosomes 4-8 were under selection for DEP. An overlapping region for early and late sowing on chromosome 8 revealed a temperature-independent effect with four candidate genes: BAM1, BAM2, HSL2, and ANT. The non-overlapping regions included six candidate genes: EMF1, EMF2, BRC1/TCP18, BZR1, NPGR1, and ERF1. Modelling showed that DEP reduces the likelihood of drought and heat stress at the expense of increased likelihood of cold stress. Accounting for DEP would improve genetic and phenotypic models of phenology.

The genetics of vigour-related traits in chickpea (Cicer arietinum L.): insights from genomic data.

KEY MESSAGE: QTL controlling vigour and related traits were identified in a chickpea RIL population and validated in diverse sets of germplasm. Robust KASP markers were developed for marker-assisted selection. To understand the genetic constitution of vigour in chickpea (Cicer arietinum L.), genomic data from a bi-parental population and multiple diversity panels were used to identify QTL, sequence-level haplotypes and genetic markers associated with vigour-related traits in Australian environments. Using 182 Recombinant Inbred Lines (RILs) derived from a cross between two desi varieties, Rupali and Genesis836, vigour QTL independent of flowering time were identified on chromosomes (Ca) 1, 3 and 4 with genotypic variance explained (GVE) ranging from 7.1 to 28.8%. Haplotype analysis, association analysis and graphical genotyping of whole-genome re-sequencing data of two diversity panels consisting of Australian and Indian genotypes and an ICRISAT Chickpea Reference Set revealed a deletion in the FTa1-FTa2-FTc gene cluster of Ca3 significantly associated with vigour and flowering time. Across the RIL population and diversity panels, the impact of the deletion was consistent for vigour but not flowering time. Vigour-related QTL on Ca4 co-located with a QTL for seed size in Rupali/Genesis836 (GVE = 61.3%). Using SNPs from this region, we developed and validated gene-based KASP markers across different panels. Two markers were developed for a gene on Ca1, myo -inositol monophosphatase (CaIMP), previously proposed to control seed size, seed germination and seedling growth in chickpea. While associated with vigour in the diversity panels, neither the markers nor broader haplotype linked to CaIMP was polymorphic in Rupali/Genesis836. Importantly, vigour appears to be controlled by different sets of QTL across time and with components which are independent from phenology.

Association Between Platelet Glycoprotein IIb/IIIa Inhibition and In-Hospital Outcomes in ST-Elevation Myocardial Infarction Patients Treated with Coronary Thrombus Aspiration: Findings from the CCC-ACS Project.

PURPOSE: Thrombus aspiration in ST-elevation myocardial infarction (STEMI) with high thrombus burden did not improve clinical outcomes. The clinical efficacy of the bailout use of platelet glycoprotein IIb/IIIa inhibitors (GPIs) in this clinical scenario remains unknown. METHODS: We assessed associations between GPI use and in-hospital major bleeds, ischemic events, and mortality among STEMI patients treated with percutaneous coronary intervention (PCI) and thrombus aspiration in a nationwide acute coronary syndrome registry (the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome project). RESULTS: A total of 5896 STEMI patients who received thrombus aspiration were identified, among which 56.3% received GPI therapy. In a 1-to-1 propensity-score-matched cohort, compared with STEMI patients not treated with GPI, GPI use was associated with a 69% increase in major in-hospital bleeds, with an odds ratio (OR) of 1.69, a 95% confidence interval (CI) of 1.08 to 2.65, and a nonsignificant reduction in ischemic events (OR: 0.61, 95% CI: 0.36 to 1.06), as well as a neutral effect on mortality (OR: 0.93, 95% CI: 0.55 to 1.58). However, among patients aged < 60 years, GPI use was associated with a reduction in ischemic events (OR: 0.27, 95% CI: 0.08 to 0.98), and no significant increase in major bleeds was observed. CONCLUSION: In a nationwide registry, routine use of GPI following thrombus aspiration was not associated with reduced in-hospital ischemic events and mortality but at the cost of increased major bleeding. However, for patients aged < 60 years, there may be a potential net benefit.

Elevated Th17 cell proportion, related cytokines and mRNA expression level in patients with hypertension-mediated organ damage: a case control study.

BACKGROUND: Immune abnormalities and inflammatory responses play critical roles in progression of hypertension. Basic studies have confirmed that Th17 cell and related cytokines are important in promoting hypertension-mediated organ damage, but few clinical evidences have been published. Therefore, our study aimed to investigate the relationship between Th17 cell and its related cytokines and hypertension-mediated organ damage in human. METHODS: This study enrolled 179 patients with hypertension (including 92 with hypertension-mediated organ damage and 87 without hypertension-mediated organ damage) and 63 healthy participants. The proportion of Th17 cells in peripheral blood mononuclear cells was measured by flow cytometry. The concentrations of interleukin-17 and interleukin-23 were detected by enzyme-linked immunosorbent assay. Real time-polymerase chain reaction was used to detect the mRNA expression levels of interleukin-17, retinoic acid-related orphan receptor (ROR) γt and signal transducer and activator of transcription-3 (STAT-3). RESULTS: The proportion of Th17 cells, the concentration of interleukin-17 and interleukin-23 and the mRNA expression levels of interleukin-17, retinoic acid-related orphan receptor γt and signal transducer and activator of transcription-3 were significantly increased in hypertension-mediated organ damage group compared with those in non-hypertension-mediated organ damage group and control group (P < 0.005). CONCLUSION: Th17 cells and their associated cytokines may be involved in hypertension-mediated organ damage formation and may be able to serve as new biomarkers of hypertension-mediated organ damage and potential therapeutic targets.

Long-term risks for cardiovascular disease and mortality across the glycaemic spectrum in a male-predominant Chinese cohort aged 75 years or older: the Kailuan study.

BACKGROUND: Ageing and diabetes are growing global health burdens. The current understanding of cardiovascular disease (CVD) and mortality risk across the glycaemic spectrum in older populations is limited. OBJECTIVES: This study sought to characterise CVD and all-cause mortality risk across the glycaemic spectrum among Chinese adults aged 75 years or older in a community-based setting over10 years. METHODS: The 3,989 adults in the Kailuan Study were aged over 75 years (median age was 79 years [interquartile range: 76-82]; 2,785 normoglycaemic, 691 prediabetic and 513 diabetic, determined by fasting blood glucose levels) at baseline, predominantly male (92.9% male) and followed until December 2019. Time-varying Cox regression and competing-risk models were used to examine the hazard ratio (HR) of incident CVD and mortality across the glycaemic exposures. RESULTS: During median follow-up of 11.3 years, 433 first CVD and 2,222 deaths were recorded. Compared with normoglycaemia, multivariable-adjusted models revealed the following: (i) prediabetes was not associated with future risks for CVD (HR: 1.17; 95% CI 0.82-1.69) and all-cause mortality (HR 1.06; 95% CI 0.70-1.60); (ii) diabetes-associated enhanced risks for CVD and all-cause mortality were mainly confined to those exhibiting low-grade inflammation (high-sensitivity C-reactive protein ≥2.0 mg/L) levels. The results were consistent after multiple sensitivity analyses. CONCLUSIONS: Among a male-predominant Chinese population aged 75 years or older, compared with normoglycaemic participants, prediabetes was not associated with an enhanced 10-year CVD and all-cause mortality risk, and diabetes-associated enhanced 10-year risk was mainly confined to individuals exhibiting low-grade inflammation.

Inhibition of gap junction communication between cells can induce apoptosis of corpus cavernosum smooth muscle in guinea pigs.

In this study, we aimed to investigate the effect of gap junction (GJ) on apoptosis of smooth muscle. Forty adult male guinea pigs were randomly divided into four groups with 10 guinea pigs in each group. Adeno-associated virus (AAV) and Gap27 were injected at the root of the corpus cavernosum. Two weeks later, the corpus cavernosum tissue was taken to be tested. The expression of Cx43 and α-SMC protein was detected by immunofluorescence and Western blotting. The content of corpus cavernosum smooth muscle was detected by Masson trichrome staining. Apoptosis was detected by TUNEL staining and Western blotting. The results showed that Gap27 did not affect Cx43 but decreased the expression of smooth muscle. The results of TUNEL staining and detection of apoptosis-related proteins showed that apoptosis was induced by Gap27. In addition, we found that corpus cavernosum injection of AAV could induce obvious apoptosis. In this study, we examined the effect of inhibition of gap junction on smooth muscle, and suggested that the decrease of gap junction function may be a potential mechanism of smooth muscle apoptosis.

LDL cholesterol levels and in-hospital bleeding in patients on high-intensity antithrombotic therapy: findings from the CCC-ACS project.

AIMS: Emerging evidence has linked cholesterol metabolism with platelet responsiveness. We sought to examine the dose-response relationship between low-density lipoprotein cholesterol (LDL-C) and major in-hospital bleeds in acute coronary syndrome (ACS) patients. METHODS AND RESULTS: Among 42 378 ACS patients treated with percutaneous coronary intervention (PCI) enrolled in 240 hospitals in the Improving Care for Cardiovascular Disease in China-ACS project from 2014 to 2019, a total of 615 major bleeds, 218 ischaemic events, and 337 deaths were recorded. After controlling for baseline variables, a non-linear relationship was observed for major bleeds, with the higher risk at lower LDL-C levels. No dose-response relationship was identified for ischaemic events and mortality. A threshold value of LDL-C <70 mg/dL was associated with an increased risk for major bleeds (adjusted odds ratio: 1.49; 95% confidence interval: 1.21-1.84) in multivariable-adjusted logistic regression models and in propensity score-matched cohorts. The results were consistent in multiple sensitivity analyses. Among ticagrelor-treated patients, the LDL-C threshold for increased bleeding risk was observed at <88 mg/dL, whereas for clopidogrel-treated patients, the threshold was <54 mg/dL. Across a full spectrum of LDL-C levels, the treatment effect size associated with ticagrelor vs. clopidogrel on major bleeds favoured clopidogrel at lower LDL-C levels, but no difference at higher LDL-C levels. CONCLUSIONS: In a nationwide ACS registry, a non-linear association was identified between LDL-C levels and major in-hospital bleeds following PCI, with the higher risk at lower levels. As the potential for confounding may exist, further studies are warranted. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02306616.

Autosomal deletion/insertion polymorphisms for global stratification analyses and ancestry origin inferences of different continental populations by machine learning methods.

A lot of population data of 30 deletion/insertion polymorphisms (DIPs) of the Investigator DIPplex kit in different continental populations have been reported. Here, we assessed genetic distributions of these 30 DIPs in different continental populations to pinpoint candidate ancestry informative DIPs. Besides, the effectiveness of machine learning methods for ancestry analysis was explored. Pairwise informativeness (In) values of 30 DIPs revealed that six loci displayed relatively high In values (>0.1) among different continental populations. Besides, more loci showed high population-specific divergence (PSD) values in African population. Based on the pairwise In and PSD values of 30 DIPs, 17 DIPs in the Investigator DIPplex kit were selected to ancestry analyses of African, European, and East Asian populations. Even though 30 DIPs provided better ancestry resolution of these continental populations based on the results of PCA and population genetic structure, we found that 17 DIPs could also distinguish these continental populations. More importantly, these 17 DIPs possessed more balanced cumulative PSD distributions in these populations. Six machine learning methods were used to perform ancestry analyses of these continental populations based on 17 DIPs. Obtained results revealed that naïve Bayes manifested the greatest performance; whereas, k nearest neighbor showed relatively low performance. To sum up, these machine learning methods, especially for naïve Bayes, could be used as the valuable tool for ancestry analysis.

Affordable Ab Initio Path Integral for Thermodynamic Properties via Molecular Dynamics Simulations Using Semiempirical Reference Potential.

Path integral molecular dynamics (PIMD) is becoming a routinely applied method for incorporating the nuclear quantum effect in computer simulations. However, direct PIMD simulations at an ab initio level of theory are formidably expensive. Using the protonated 1,8-bis(dimethylamino)naphthalene molecule as an example, we show in this work that the computational expense for the intramolecular proton transfer between the two nitrogen atoms can be remarkably reduced by implementing the idea of reference-potential methods. The simulation time can be easily extended to a scale of nanoseconds while maintaining the accuracy on an ab initio level of theory for thermodynamic properties. In addition, postprocessing can be carried out in parallel on massive computer nodes. A 545-fold reduction in the total CPU time can be achieved in this way as compared to a direct PIMD simulation at the same ab initio level of theory.

A recurrent neural network using historical data to predict time series indoor PM2.5 concentrations for residential buildings.

Due to the severe outdoor PM2.5 pollution in China, many people have installed air-cleaning systems in homes. To make the systems run automatically and intelligently, we developed a recurrent neural network (RNN) that uses historical data to predict the future indoor PM2.5 concentration. The RNN architecture includes an autoencoder and a recurrent part. We used data measured in an apartment over the course of an entire year to train and test the RNN. The data include indoor/outdoor PM2.5 concentration, environmental parameters and time of day. By comparing three different input strategies, we found that a strategy employing historical PM2.5 and time of day as inputs performed best. With this strategy, the model can be applied to predict the relatively stable trend of indoor PM2.5 concentration in advance. When the input length is 2 h and the prediction horizon is 30 min, the median prediction error is 8.3 µg/m3 for the whole test set. For times with indoor PM2.5 concentrations between (20,50] µg/m3 and (50,100] µg/m3 , the median prediction error is 8.3 and 9.2 µg/m3 , respectively. The low prediction error between the ground-truth and predicted values shows that the RNN can predict indoor PM2.5 concentrations with satisfactory performance.

Highly Monodisperse Cu-Sn Alloy Nanoplates for Efficient Nitrophenol Reduction Reaction via Promotion Effect of Tin.

The hexagonal copper-tin alloy (Cu-Sn) nanoplates were synthesized using a high temperature solvent method, the length of six equilateral edges of hexagonal Cu-Sn nanoplates was 23 nm, and the thickness was 13 nm. The obtained hexagonal Cu-Sn nanoplates were highly monodisperse and allowed the formation of nanoarrays arranged with long-range order. The hexagonal Cu-Sn nanoplates exhibited high catalytic activity on catalytic hydrogenation of 4-nitrophenol to 4-aminophenol. Due to the promotion effect of Sn, the apparent rate constant (ka) of hexagonal Cu-Sn nanoplates was three times that of Cu nanoparticles. The density functional theory (DFT) calculations and experimental results demonstrated that Sn could promote the coordination process of -NO2 of 4-nitrophenol with Cu-Sn nanoplates and contribute to activation of 4-nitrophenol. In addition, the hexagonal Cu-Sn nanoplates showed high stability and reusability for the reduction reaction, good adaptability in different pH and the ionic strength, and wide applicability for the degradation of methylene blue, methyl orange, and rhodamine B, even in the industrial wastewater, suggesting that the Cu-Sn nanoplates are promising catalysts in organic industry wastewater treatment.

Mapping resistance to Phytophthora root rot identifies independent loci from cultivated (Cicer arietinum L.) and wild (Cicer echinospermum P.H. Davis) chickpea.

KEY MESSAGE: Major QTL for Phytophthora root rot resistance have been identified in three mapping populations with independent sources of resistance contributed by C. echinospermum and C. arietinum. Phytophthora root rot (PRR) caused by the oomycete Phytophthora medicaginis is a major soil-borne disease of chickpea in Australia. With no economic in-crop control of PRR, a genetic approach to improve resistance is the most practical management option. Moderate field resistance has been incorporated in the cultivated C. arietinum variety, Yorker, and a higher level of resistance has been identified in a derivative of wild chickpea (C. echinospermum, interspecific breeding line 04067-81-2-1-1). These genotypes and two other released varieties were used to develop one intra-specific and two interspecific F6-derived recombinant inbred line mapping populations for genetic analysis of resistance. The Yorker × Genesis114 (YG), Rupali × 04067-81-2-1-1 (RB) and Yorker × 04067-81-2-1-1 (YB) populations were genotyped using genotyping-by-sequencing and phenotyped for PRR under three field environments with a mixture of 10 P. medicaginis isolates. Whole-genome QTL analysis identified major QTL QRBprrsi01, QYBprrsi01, QRBprrsi03 and QYBprrsi02 for PRR resistance on chromosomes 3 and 6, in RB and YB populations, respectively, with the resistance source derived from the wild Cicer species. QTL QYGprrsi02 and QYGprrsi03 were also identified on chromosomes 5 and 6 in YG population from C. arietinum. Aligning QTL regions to the corresponding chickpea reference genome suggested that the resistance source from C. arietinum and C. echinospermum may be different. The findings from this study provide tools for marker-assisted selection in chickpea breeding and information to assist the development of populations suitable for fine-mapping of resistance loci to determine the molecular basis for PRR resistance in chickpea.

THE ASSOCIATION BETWEEN BODY MASS INDEX AND SUBCLINICAL THYROID DYSFUNCTION IN DIFFERENT SEXES OF CHINESE.

Objective: To study subclinical thyroid dysfunction (SCTD)-subclinical hyperthyroidism and subclinical hypothyroidism-in Chinese patients in relation to body mass index (BMI) and to determine whether a difference between sexes exists. Methods: This cross-sectional study recruited 13,503 healthy participants (8,345 male, 5,158 female) who participated in a health examination. Clinical data, including anthropometric measurements and serum parameters, were collected. The association between SCTD and the BMI of each sex was analyzed separately by stratifying the data by SCTD type and regarding BMI as a categorical or as a continuous variable in different models. The odds ratio of SCTD was calculated from binary logistic regression models. Results: The prevalence of both subclinical hyperthyroidism and subclinical hypothyroidism was significantly lower in males compared to females. For subclinical hypothyroidism, we found no significant association with BMI in females. In males, there was a significant negative relationship between BMI and subclinical hypothyroidism. For subclinical hyperthyroidism, we did not find any significant relationship with BMI in either sex after stratifying the data and treating BMI as a categorical or as a continuous variable. Conclusion: For subclinical hyperthyroidism, no significant effect was found in either sex. For subclinical hypothyroidism, high BMI was associated with lower rates of subclinical hypothyroidism in males, and no significant correlation was found in females. The mechanism of this sex-specific association between BMI and SCTD needs more verification. Abbreviations: ALT = alanine aminotransferase; AST = aspartate aminotransferase; BMI = body mass index; BUN = blood urea nitrogen; CI = confidence interval; Cr = creatinine; DBP = diastolic blood pressure; FG = fasting glucose; FT3 = free triiodothyronine; FT4 = free thyroxine; HDL = high-density lipoprotein; LDL = low-density lipoprotein; OR = odds ratio; SBP = systolic blood pressure; SCTD = subclinical thyroid dysfunction; TBIL = total bilirubin; TC = total cholesterol; TG = triglyceride; TSH = thyroid-stimulating hormone; UA = uric acid; WBC = white blood cell; WC = waist circumference.

PTEN-Induced Putative Kinase 1 (PINK1)/Parkin-Mediated Mitophagy Protects PC12 Cells Against Cisplatin-Induced Neurotoxicity.

BACKGROUND The pathogenesis of chemotherapy-induced neuropathy, a dose-dependent adverse effect of cisplatin, involves mitochondrial dysfunction. PTEN-induced putative kinase 1 (PINK1)/Parkin-mediated mitophagy removes damaged mitochondria under various pathological conditions. The objective of this study was to determine mitophagy status and its effects on mitochondrial function and neuronal cell damage after cisplatin treatment using an in vitro model of cisplatin-induced neurotoxicity. MATERIAL AND METHODS PC12 cells were transfected with Parkin or Parkin siRNA using lentiviral particles and Lipofectamine 3000™, respectively, and then were exposed to 10 µM cisplatin. The expression of autophagic proteins was measured by Western blot analysis. Mitophagy in PC12 cells was detected by confocal microscopy analysis of mitochondria-lysosomes colocalization and autophagic flux. The effects of PINK1/Parkin-mediated mitophagy on cisplatin-induced neurotoxicity were assessed via mitochondrial function, neuritic length, nuclear diameter, and apoptosis. RESULTS Cisplatin activated PINK1/Parkin-mediated mitophagy in PC12 cells. Autophagic flux analysis revealed that cisplatin inhibits the late stage of the autophagic process. The knockdown of Parkin suppressed cisplatin-induced mitophagy, aggravating cisplatin-induced depolarization of mitochondria, cellular ATP deficits, reactive oxygen species outburst, neuritic shortening, nuclear diameter reduction, and apoptosis, while Parkin overexpression enhanced mitophagy and reversed these effects. CONCLUSIONS PINK1/Parkin-regulated mitophagy can protect against cisplatin-related neurotoxicity, suggesting therapeutic enhancement of mitophagy as a potential intervention for cisplatin-induced peripheral neuropathies. The interference of cisplatin with autophagosome-lysosome fusion may be partly responsible for cisplatin-induced neurotoxicity.

The Construction of Sustained-Release Systems of Tanshinone IIA and Sodium Tanshinone IIA Sulfonate by SBA-15 Mesoporous Material.

The basic problems of the low dissolution rate of Tanshinone IIA (TSN) and the instability and precipitation of sodium tanshinone IIA sulfonate (STS) injection limit their usage in clinical. For these facts, the study aims to improve the dissolution rate of TSN and to enhance the sustained release effects of TSN and STS by using SBA-15 mesoporous molecular sieve as a drug carrier. Furthermore, controlling the pore size of SBA-15 and using different loaded methods to achieve expectations and provide a novel scheme for existing Danshen formulations. The effect of loading methods on drug loading efficiency (DL%), as well as the influence of the pore size of SBA-15s, the drug polarities and release mediums on drug loading and release behaviors were analyzed. It was found that the DL% was enhanced with the enlargement of the pore size, and was higher of TSN than STS. The in vitro tests of drug-loaded SBA-15s confirmed that the dissolution rate of TSN was improved obviously as compared with pure TSN. Moreover, SBA-15s prolonged the release times up to 12 h of TSN and 60 h of STS and promoted the sustained-release behaviors by decreasing the pore size. To ascertain the kinetic mechanisms of these samples, the Korsmeyer-Peppas release model was employed and the fitted results indicated that TSN/SBA-15s followed Fickian diffusion and non-Fickian transport was the predominant kinetic release mechanisms for STS/SBA-15s.