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Soybean mosaic virus (SMV), an RNA virus, is the most common and destructive pathogenic virus in soybean fields. The newly developed CRISPR/Cas immune system has provided a novel strategy for improving plant resistance to viruses; hence, this study aimed to engineer SMV resistance in soybean using this system. Specifically, multiple sgRNAs were designed to target positive- and/or negative-sense strands of the SMV HC-Pro gene. Subsequently, the corresponding CRISPR/CasRx vectors were constructed and transformed into soybeans. After inoculation with SMV, 39.02%, 35.77%, and 18.70% of T1 plants were confirmed to be highly resistant (HR), resistant (R), and mildly resistant (MR) to SMV, respectively, whereas only 6.50% were identified as susceptible (S). Additionally, qRT-PCR and DAS-ELISA showed that, both at 15 and 30 d post-inoculation (dpi), SMV accumulation significantly decreased or was even undetectable in HR and R plants, followed by MR and S plants. Additionally, the expression level of the CasRx gene varied in almost all T1 plants with different resistance level, both at 15 and 30 dpi. Furthermore, when SMV resistance was evaluated in the T2 generation, the results were similar to those recorded for the T1 generation. These findings provide new insights into the application of the CRISPR/CasRx system for soybean improvement and offer a promising alternative strategy for breeding for resistance to biotic stress that will contribute to the development of SMV-immune soybean germplasm to accelerate progress towards greater soybean crop productivity. [ABSTRACT FROM AUTHOR]

Background: The relation between mental disorders (MDs) and infertility can be reciprocal. But exactly which MD affects infertility remains controversial. Our aim was to use Mendelian randomization (MR) to explore bidirectional causality between 15 MDs and male infertility and female infertility. Methods: The data of MDs, male infertility, and female infertility were derived from published genome-wide association studies (GWAS). The inverse variance weighted method was considered to be the main analytical approach. Sensitivity analysis was performed using MR-Egger, Cochran's Q, radial MR, and MRPRESSO tests. Results: Our results found that mood disorders (OR, 1.4497; 95% CI, 1.0093 -- 2.0823; P = 0.0444) and attention deficit hyperactivity disorder (OR, 1.3921; 95% CI, 1.0943 -- 1.7709; P = 0.0071) were positively correlated with male infertility, but obsessive-compulsive disorder (OR, 0.8208; 95% CI, 0.7146 -- 0.9429; P = 0.0052) was negatively associated with male infertility. For females, anorexia nervosa (OR, 1.0898; 95% CI, 1.0070 -- 1.1794; P = 0.0329), attention deficit hyperactivity disorder (OR, 1.1013; 95% CI, 1.0041 -- 1.2079; P = 0.0406), and major depressive disorder (OR, 1.1423; 95% CI, 1.0213 -- 1.2778; P = 0.0199) increased risk of infertility. In reverse relationship, female infertility increased the incidence of bipolar disorder (OR, 1.0009; 95% CI, 1.0001 -- 1.0017; P = 0.0281). Conclusion: We demonstrated the association between five MDs and male or female infertility. Female infertility was also found to be associated with an increased risk of one MD. We look forward to better designed epidemiological studies to support our results. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of cetagliptin (CAS number:2243737-33-7) in Chinese patients with type 2 diabetes mellitus (T2DM). A population PK/PD model was developed to quantify the PK and PD characteristics of cetagliptin in patients. Materials and methods: 32 Chinese adults with T2DM were enrolled in this study. The subjects were randomly assigned to receive either cetagliptin (50 mg or 100 mg), placebo, or sitagliptin (100 mg) once daily for 14 days. Blood samples were collected for PK and PD analysis. Effects on glucose, insulin, C-peptide, and glucagon were evaluated following an oral glucose tolerance test (OGTT) (day15). Effects on HbA1c and glycated albumin (GA), and safety assessments were also conducted. Meanwhile, a population PK/PD model was developed by a sequential two-step analysis approach using Phoenix. Results: Following multiple oral doses, cetagliptin was rapidly absorbed and the mean half-life were 34.9-41.9 h. Steady-state conditions were achieved after 1 week of daily dosing and the accumulation was modest. The intensity and duration of DPP-4 inhibition induced by 50 mg cetagliptin were comparable with those induced by sitagliptin, and 100 mg cetagliptin showed a much longer sustained DPP-4 inhibition (≥80%) than sitagliptin. Compared with placebo group, plasma active GLP-1 AUEC0-24h increased by 2.20- and 3.36-fold in the 50 mg and 100 mg cetagliptin groups. A decrease of plasma glucose and increase of insulin and C-peptide were observed following OGTT in cetagliptin groups. Meanwhile, a tendency of reduced GA was observed, whereas no decreasing trend was observed in HbA1c. All adverse events related to cetagliptin and sitagliptin were assessed as mild. A population PK/PD model was successfully established. The two-compartment model and Sigmoid-Emax model could fit the observed data well. Total bilirubin (TBIL) was a covariate of volume of peripheral compartment distribution (V2), and V2 increased with the increase of TBIL. Conclusions: Cetagliptin was well tolerated, inhibited plasma DPP-4 activity, increased plasma active GLP-1 levels, and exhibited a certain trend of glucoselowering effect in patients with T2DM. The established population PK/PD model adequately described the PK and PD characteristics of cetagliptin. [ABSTRACT FROM AUTHOR]

Mechanically strong magnesium-doped Ca-silicate bioceramic scaffolds have many advantages in repairing large segmental bone defects. Herein we combine β-TCP with 6 mol% magnesium-doped calcium silicate (Mg6) at three different ratios (TCP, TCP + 15 %Mg6, TCP + 85 %Mg6) to find an appropriate ratio which can exert considerable influence on bone regeneration. In this study, the bioceramic scaffolds were assessed for mechanical strength, bioactive ion release, biocompatibility, and osteogenic capacity through in vitro testing. Additionally, the potential for promoting bone regeneration was investigated through in vivo implantation of porous tube-like scaffolds. The results showed that the compressive strength increased with the augmentation of Mg6 component. Especially the compressive strength of the TCP + 85 %Mg6 group reached 38.1 ± 3.8 MPa, three times that of the other two groups. Furthermore, extensive in vivo investigations revealed that the TCP + 85 %Mg6 bioceramic scaffolds were particularly beneficial for the osteogenic capacity of critical-sized femoral defects (20 mm in length). Altogether, magnesium doping in bioceramic implants is a promising strategy to provide stronger mechanical support and enhance osteogenesis to accelerate the repair of large defects. [ABSTRACT FROM AUTHOR]

Background: Although immune checkpoint inhibitors (ICIs) show a significant overall survival advantage over standard advanced renal cell carcinoma (aRCC) therapies, tumor response to these agents remains poor. Some studies have shown that combination therapy including an ICI appears to be the best treatment; however, the overall benefit in terms of efficacy and toxicity still needs to be assessed. Thus, we performed a network meta-analysis to evaluate the differences in the efficacy of several combinations that include an ICI to provide a basis for clinical treatment selection. Methods: We conducted a thorough search of PubMed, EMBASE, and the Cochrane Library for articles from January 2010 to June 2023. R 4.4.2 and STATA 16.0 were used to analyze data; hazard ratio (HR) and odds ratio (OR) with 95% confidence intervals (CI) were used to assess the results. Results: An indirect comparison showed that nivolumab plus cabozantinib and pembrolizumab plus lenvatinib were the most effective treatments for progression-free survival (PFS), with no significant differences between the two interventions (HR, 1.31; 95% CI, 0.96-1.78; P=0.08); rank probability showed that pembrolizumab plus lenvatinib had a 57.1% chance of being the preferred treatment. In the absence of indirect comparisons between pembrolizumab plus axitinib, nivolumab plus ipilimumab, avelumab plus axitinib, nivolumab plus cabozantinib, and pembrolizumab plus lenvatinib, pembrolizumab plus axitinib (40.2%) was the best treatment option for overall survival (OS). Compared to pembrolizumab plus lenvatinib, nivolumab plus ipilimumab (OR, 0.07; 95% CI, 0.01-0.65; P=0.02) and pembrolizumab plus axitinib (OR, 0.05; 95% CI, 0.00-0.78; P<0.001) had a lower incidence of overall adverse events (AEs). Conclusion: Pembrolizumab plus lenvatinib and pembrolizumab plus axitinib resulted in the highest PFS and OS rates, respectively. Pembrolizumab plus axitinib may be the best option when AEs are a concern. [ABSTRACT FROM AUTHOR]

Objective: This network meta-analysis (NMA) was conducted to compare and rank the effects of training interventions including aerobic exercise (AE), resistance training (RT), combined aerobic and resistance training (CT), and high-intensity interval training (HIIT) on vital metabolic indicators in adults with overweight and obesity. Methods: PubMed, Cochrane, Embase, and Web of Science were searched from 1990 to February 2023. Articles were included if they described randomized controlled trials (RCTs) examining the effects of exercise training on anthropometry parameters, lipid profiles, glucose metabolism, blood pressure, and cardiorespiratory fitness in adults with overweight and obesity. Weighted mean difference with 95% CI was calculated. Results: A total of 28 studies with 1,620 patients were included. Results revealed that AE exerts best effects on weight loss (−2.35 [−4.05, −0.64]) and body mass index (−0.9 [−1.38, −0.42]), while HIIT is the most effective in reducing waist circumference (−5.93 [10.71, −1.15]), percentage body fat (−3.93 [−5.73, −2.12]), serum triglycerides (−20.55 [−37.20, −3.91]), and fasting blood glucose (−14.31 [−22.47, −6.16]) and improving VO2 max (7.41 [4.37, 10.45]). However, no significant benefit was observed in terms of total cholesterol and blood pressure. Conclusions: AE is the optimal exercise type for reducing body weight and BMI, while HIIT exerts the most beneficial effects on improving body composition, cardiorespiratory fitness, and metabolic abnormalities in adults with overweight and obesity [ABSTRACT FROM AUTHOR]

Background: Studies using novel antiandrogens (NAA) in patients with metastatic castration-resistant prostate cancer (mCRPC) have shown overall survival benefit. As patients develop resistance to NAA therapy, the poly(ADP-ribose) polymerase inhibitor (PARPi) olaparib in combination with NAA may become a promising therapy. However the overall benefit of olaparib monotherapy or combination therapy still needs to be evaluated. Therefore, we performed a network meta-analysis to assess the efficacy and toxicity between olaparib, olaparib combined with abiraterone and NAA. Methods: We searched PubMed, EMBASE, the Cochrane Library and American Society of Clinical Oncology (ASCO) University Meeting abstracts for randomized controlled trials reporting olaparib and NAA from 2010 up to March, 2023. Network meta-analysis using Stata 16.0 and R 4.4.2, hazard ratios (HR) with 95% confidence intervals (CI) were used to assess the results. Results: Four trials reported olaparib, olaparib plus abiraterone and apalutamide plus abiraterone. radiographic progression-free survival (rPFS) was significantly lower in patients on apalutamide plus abiraterone compared to olaparib (HR, 1.43; 95% CI, 1.06-1.93). rPFS was similar for olaparib plus abiraterone and olaparib (HR, 1.35; 95% CI, 0.99-1.84); likewise, olaparib plus abiraterone and apalutamide plus abiraterone were similar (HR, 1.06; 95% CI, 0.83-1.35). In addition, there was no significant difference between the three interventions for OS. But olaparib has the highest probability of being a preferred treatment for improving rPFS and OS. Conclusion: rPFS was in favor of olaparib compared with apalutamide plus abiraterone. But there were no difference between olaparib plus abiraterone and either olaparib or apalutamide plus abiraterone. Apalutamide plus abiraterone might be the most preferred intervention in cases where AEs are involved. [ABSTRACT FROM AUTHOR]

Introduction: Brown adipose tissue (BAT) is mainly responsible for mammalian non-shivering thermogenesis and promotes energy expenditure. Meanwhile, similar to white adipose tissue (WAT), BAT also secretes a variety of adipokines to regulate metabolism through paracrine, autocrine, or endocrine ways. The chemokine C-X-C motif chemokine ligand-13 (CXCL13), a canonical B cell chemokine, functions in inflammation and tumor-related diseases. However, the role of CXCL13 in the adipose tissues is unclear. Methods: The expression of CXCL13 in BAT and subcutaneous white adipose tissue (SWAT) of mice under cold stimulation were detected. Local injection of CXCL13 into BAT of normal-diet and high-fat-diet induced obese mice was used to detect thermogenesis and determine cold tolerance. The brown adipocytes were treated with CXCL13 alone or in the presence of macrophages to determine the effects of CXCL13 on thermogenic and inflammation related genes expression in vitro. Results: In this study, we discovered that the expression of CXCL13 in the stromal cells of brown adipose tissue significantly elevated under cold stimulation. Overexpression of CXCL13 in the BAT via local injection could increase energy expenditure and promote thermogenesis in obese mice. Mechanically, CXCL13 could promote thermogenesis via recruiting M2 macrophages in the BAT and, in the meantime, inhibiting pro-inflammatory factor TNFα level. Discussion: This study revealed the novel role of adipose chemokine CXCL13 in the regulation of BAT activity and thermogenesis. [ABSTRACT FROM AUTHOR]

Background: SHR8554 is a novel μ-opioid receptor-biased agonist. It has analgesic effects by selectively activating the G protein-coupled pathway. Additionally, it can weakly activate the ß-arrestin-2 pathway, resulting in a limited number of side effects, such as gastrointestinal inhibition. Previous studies have shown that SHR8554 has good analgesic effects, safety and tolerability, but the pharmacokinetic characteristics of SHR8554 in humans have not been reported. This study was designed to investigate the pharmacokinetics and safety of SHR8554 in healthy Chinese male subjects. Methods: A single 1 mg/41.3 μCi intravenous dose of [14C]SHR8554 was administered to six healthy male subjects. Blood, urine and faecal samples were collected at continuous time points to analyse SHR8554 parent drug levels and their metabolites. The total radioactivity in blood, plasma, urine and faeces was detected by using a liquid scintillation counter. The dynamic changes of SHR8554 and its metabolite concentration were by liquid chromatographytandem mass spectrometry (LC/MS), and then pharmacokinetic analysis. The safety of the drug on the subjects was also observed after a single intravenous injection. Results: The total recovery of radioactivity in urine and faeces was 99.68% ± 0.79% in 216 h, including 76.22% ± 1.12% in urine and 23.46% ± 1.36% in faeces. Seventeen major metabolites in blood, urine and faeces were analysed and identified. The main metabolic pathways of SHR8554 in the human body involve 1) N-dealkylation; 2) O-deethylation; 3) mono-oxidation; 4) glucuronidation, etc. The primary mechanism of SHR8554 clearance in the human body is through urinary excretion, primarily in its parent drug and metabolite forms. The drug has good safety, and no serious adverse effects were observed. Conclusion: SHR8554 showed favourable pharmacokinetic characteristics and safety profiles in this study. SHR8554 is extensively metabolized in human body. The main metabolic pathways include N-dealkylation and O-deethylation, as well as mono-oxidation and glucuronidation. The main excretion route of SHR8554 and its metabolites is through urine. Clinical Trial Registration: http://www.chinadrugtrials.org.cn/, identifier CTR20220450 [ABSTRACT FROM AUTHOR]

Background: Previous studies have suggested that proton pump inhibitors could impair the antiplatelet effect of clopidogrel. It is uncertain whether ilaprazole affects the antiplatelet effect of clopidogrel. This study aimed to determine the drug-drug interaction between ilaprazole and clopidogrel. Methods: A randomized crossover trial of 40 healthy subjects was performed. Clopidogrel was administered alone or in combination with ilaprazole for 7 days. The maximal platelet aggregation (MPA) to 5 µmol/L adenosine diphosphate was measured by light transmission aggregometry and the platelet reactivity index (PRI) was determined by vasodilator-stimulated phosphoprotein P2Y12 assay. High on-treatment platelet reactivity (HOPR) was defined as a MPA of >40%. The inhibition of platelet aggregation (IPA) and PRI in the two phases were compared between two regimens after the last dosing. Results: IPA was comparable between the two regimens at 0, 10 and 24 h (p > 0.05), but higher at 4 h in the clopidogrel alone regimen compared with that in the combined treatment regimen (75.66 ± 18.44% vs. 70.18 ± 17.67%, p = 0.031). The inhibition of PRI was comparable between the two regimens at 0 and 24 h. There were no significant differences in the area under the time-IPA% curve (AUC) or the incidence of HOPR at all time-points between the two regimens. Conclusion: In healthy subjects, ilaprazole has limited effect on the pharmacodynamics of clopidogrel and it may not be clinically relevant. [ABSTRACT FROM AUTHOR]

A novel adsorbent based on polyurethane foam (PUF) with high density of amino groups was studied for Pb(II) removal. Polyethyleneimine (PEI) was used as functional reagent to modify the surface of PUF. The PEI modified PUF (PEI-PUF) was characterized by FTIR, SEM, XPS and elementary analysis and used for removal of Pb(II) ion from aqueous solution. The effects of equilibrium time, pH of the solution, initial Pb(II) concentration and temperature were investigated. PEI-PUF-10 and PEI-PUF-30 with different PEI content exhibited superior adsorption performance of Pb(II). Compared with PEI-PUF-10, PEI-PUF-30 has a faster adsorption rate, shorter equilibrium time and higher adsorption capacity, which may be due to the high content of PEI and the easily accessible active sites. The maximum adsorption capacity of Pb(II) on PEI-PUF-10 and PEI-PUF-30 were 98.1 and 183.0 mg g-1, respectively. The adsorption of Pb(II) on PEI-PUF was highly pH dependent and endothermic. After five cycles of adsorption/desorption, the adsorption capacity of Pb(II) on PEI-PUF-30 only showed a slight loss, which indicated that the adsorbents can be regenerated and reused for practical application. [ABSTRACT FROM AUTHOR]

Secretion of granular glands from the skin of amphibians is a fascinating resource of active substances, particularly for cancer therapy in clinical practice of Traditional Chinese Medicine. A variety of anti‑tumor peptides have been isolated from different toads and frogs; however, no anti‑tumor peptides are reported in toad venom of Bufo gargarizans. Firstly, soluble fraction from fresh toad venom (FTV) was compared with that from dried toad venom (DTV), using HPLC analysis. It was revealed that FTV has a different HPLC chromatography compared with DTV. Soluble fraction of FTV is more toxic to SH‑SY5Y cells than that of DTV, as evaluated by MTT assay. Secondly, it was identified that protein components from soluble fractions of FTV and DTV possess different patterns by SDS‑PAGE analysis, and proteins from FTV are also more toxic than that from DTV. Thirdly, an immobilized basic fibroblast growth factor (bFGF) affinity column was used to isolate bFGF‑binding components from soluble fraction of FTV, and it was identified that bFGF‑binding components prohibited bFGF‑dependent neurite growth of SH‑SY5Y cells. Finally, it was identified that bFGF‑binding components activated apoptosis via upregulation of caspase‑3 and caspase‑8 expression in SH‑SY5Y cells. These data suggest that FTV contains active components that interact with bFGF and activate apoptosis in SH‑SY5Y cells. [ABSTRACT FROM AUTHOR]

With the development of society and science technology, the information security becomes more and more important for people and nation. In this paper, we focus on the technology of iris-face fusion in multi-mode sense in order to find an algorithm to get a better recognition performance. Firstly, we introduce the feature extraction of iris and face, and fusion the features using different algorithms. By simulation, we find out the recognition performance with different fusion methods, which provide some new conclusions. In order to improve the performance of recognition system, we classify these features with fisher discriminant analysis again. Then we analyze the security of recognition system from the aspect of influence of leak in biology features. Finally, experiments were designed to demonstrate the effectiveness of the proposed algorithms. [ABSTRACT FROM AUTHOR]

Active shape model (ASM) is an image searching method based on statistical model, which is widely used to extract features. The classical ASM model includes the shape model and the local profile model. The main merit of ASM model is using statistics to contribute model of specific target image, by introducing prior knowledge on awaiting extraction target object, limiting the searching result in the variable range. These characteristics make it suitable for any similar object's feature. Experimental results show that the algorithm can extract facial features rapidly and have higher accuracy. [ABSTRACT FROM AUTHOR]

Agricultural pollution has become the dominant source of water pollution in China and the carbon reduction in agricultural aspect is pressing. Based on list analysis method, the COD, TN and TP in agriculture in 28 provinces in China from 1995 to 2010 were evaluated and compared. By dint of directional distance function, the economics mechanism to reduce carbon emission was discussed. The reduction efficiency and potential of three kinds of pollutants were estimated. The regression indicates that the educational degree, income level and work play a crucial role in carbon emission. [ABSTRACT FROM AUTHOR]

In this paper, a novel cataluminescence (CTL)-based sensor array consisting of nine types of catalytic materials is developed for the recognition of several harmful gases, namely carbon monoxide, acetone, chloroform and toluene. First, the experimental setup is constructed by using sensing nanomaterials, a heating plate, a pneumatic pump, a gas flow meter, a digital temperature device, a camera and a BPCL Ultra Weak Chemiluminescence Analyzer. Then, unique CTL patterns for the four types of harmful gas are obtained from the sensor array. The harmful gases are successful recognized by the PCA method. The optimal conditions are also investigated. Finally, experimental results show high sensitivity, long-term stability and good linearity of the sensor array, which combined with simplicity, make our system a promising application in this field. [ABSTRACT FROM AUTHOR]