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Objective To explore the effect of active vitamin D on renin, (pro) renin receptor (PRR) and NF-κB in rat renal tubular epithelial (NRK-52E) cells in high glucose conditions and elucidate the role of NF-κB. Methods NRK-52E cells were cultured in vitro and divided into 7 groups of control, high glucose, high glucose + PDTC (pyrrolidinedithiocarbamate ammonium) and high glucose + 0.1/1/10/100 nM paricalcitol. mRNA and protein expression of renin, PRR and NF-κB p65 in each group were detected by quantitative polymerase chain reaction (qPCR) and Western blot. ChIP-qPCR was utilized for detecting the relationship between NF-κB p65 and the promoter of renin. Results The expressions of renin, PRR and NF-κB spiked in high-glucose group as compared with control group (P

Objective To lay the groundwork for formulating novel immunotherapies through understanding the regulatory role of ferroptosis and its function in immune microenvironment in ANCA-associated vasculitis (AAV) with renal injury. Methods Kidney data sets on AAV were downloaded from the database of Gene Expression Omnibus (GEO). Based upon the results of differential expression, consensus clustering algorithm was employed for identifying the subtypes of iron mortality. Single sample gene set enrichment analysis (ssGSEA) and gene set variation analysis (GSVA) were performed for evaluating the immune invasion and signaling pathways of subtypes. Key ferroptosis-related genes (FRGs) were further screened by LASSO and SVM-RFE algorithms and verified by independent data sets. CIBERSORT was utilized for assessing the abundance of infiltrating immune cells for FRGs. Finally a clinical diagnostic model of FRGs was constructed by rsm package. And the correlation between FRGs and renal function was examined by Nephroseq V5 database. Results Twenty-four ferroptosis related genes were significantly differentially expressed in AAV with kidney injury. Unsupervised cluster analysis revealed the regulatory patterns of two different ferroptosis subtypes with significant differences in gene expression, immune infiltration and biological functional pathways. A set of FRGs composed of ALOX5, CD44, CRYAB, TP53, and FTH1 was selected by two machine learning algorithms. It could effectively distinguish AAV with kidney injury from normal control group. CCR, macrophage and HLA were correlated positively with FRGs. Area under ROC curve of clinical diagnostic model constructed by FRGs was 0. 961. FRGs were correlated negatively with glomerular filtration rate (GFR). However, except for CRYAB and FTH1, other FRGs were correlated positively with serum creatinine (Scr). It implicated their potential relevance to renal injury in ANCA-associated vasculitis (AAV) and their potential as prognostic biomarkers. Conclusions Ferroptosis in AAV with kidney injury is correlated closely with immune microenvironment. It provides rationales for devising new treatments for AAV with kidney injury through a better understanding the pattern of ferroptosis.

Fusarium wilt in Cymbidium ensifolium, caused by Fusarium oxysporum, is highly contagious and poses a severe hazard. It significantly reduces the ornamental value of C. ensifolium and causes substantial economic losses in agricultural production. Nucleotide-binding site–leucine-rich repeat (NBS-LRR) genes are key regulatory factors in plant disease resistance responses, playing vital roles in defending against pathogen invasions. In our study, we conducted a comprehensive analysis of the NBS-LRR gene family in the genome of Cymbidium ensifolium. Phylogenetic analysis identified a total of 31 NBS-LRR genes encoding NB-ARC proteins, which were categorized into five classes (CNL, CN, NL, N, RNL) based on their protein structural domains. These genes were found to be unevenly distributed across eight chromosomes. Physicochemical analysis revealed significant variances in molecular weight and sequence length among the family members. Subcellular localization results indicated that most genes primarily reside in the cytoplasm and cell membrane, suggesting that the primary sites of disease resistance responses may be the cell membrane and cyto-plasm. Furthermore, noticeable disparities were observed in gene structures and conserved motifs among different categories of family genes. Promoter analysis indicated that cis-regulatory elements are mainly associated with plant stress, jasmonic acid, gibberellin, and other development-related factors, suggesting that CeNBS-LRR genes mainly resist external stress through hormones such as abscisic acid and jasmonic acid. We characterized twenty-seven CeNBS-LRR gene expression patterns of healthy C. ensifolium at different periods after Fusarium wilt infection, and found that those genes exhibit a temporospatial expression pattern, and that their expression is also responsive to Fusarium wilt infection. By analyzing the expression pattern via transcriptome and qRT-PCR, we speculated that JL006442 and JL014305 may play key roles in resisting Fusarium wilt. This study lays the groundwork and holds considerable significance as a reference for identifying disease-resistant genes and facilitating genetic breeding in C. ensifolium.

IntroductionTriptolide (TPL) is a promising plant-derived compound for clinical therapy of multiple human diseases; however, its application was limited considering its toxicity.MethodsTo explore the underlying molecular mechanism of TPL nephrotoxicity, a network pharmacology based approach was utilized to predict candidate targets related with TPL toxicity, followed by deep RNA-seq analysis to characterize the features of three transcriptional elements include protein coding genes (PCGs), long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) as well as their associations with nephrotoxicity in rats with TPL treatment.Results & DiscussionAlthough the deeper mechanisms of TPL nephrotoxcity remain further exploration, our results suggested that c-Jun is a potential target of TPL and Per1 related circadian rhythm signaling is involved in TPL induced renal toxicity.

Improved knowledge on the regulation of reproductive diapause in Coccinella septempunctata, an important predator of aphids, is crucial for improving shelf-life and mass production of the ladybeetles. In many insects, the absence of juvenile hormone (JH) is a central regulator of reproductive diapause. JH is principally degraded by JH esterase (JHE) and JH epoxide hydrolase (JHEH). Previous studies have shown that genes encoding these enzymes were upregulated in early diapause of C. septempunctata, but whether increased JH degradation contributes to the reduction of JH levels and facilitates reproductive diapause remains unknown. Here, we investigate the role of JH and JH degradation genes during reproductive diapause in C. septempunctata females. Applying methoprene, a JH analogue, to the diapause preparation females clearly elevated JH signaling and reversed diapause program, suggesting that a lower level of JH is critical for the induction of reproductive diapause in the ladybeetle. Full-length cDNA sequences of JHE and JHEH were cloned and characterized, and their deduced proteins contain all the conserved active domains and typical motifs as identified in other insects. The expressions of JHE and JHEH were both significantly increased in diapause preparation and remained at a high level for a period throughout diapause, and then decreased after the termination of diapause. Knocking down these JH degradation genes clearly increased the expression levels of JH-inducible genes Krüppel-homolog 1 (Kr-h1) and vitellogenin (Vg), indicating an elevated JH level. Simultaneously, silencing JH degradation genes distinctly reduced diapause-related features and promotes reproduction, indicated by accelerated ovary growth, yolk deposition, and suppressed lipid accumulation. These results indicate that the enhanced JH degradation plays a critical role in regulating reproductive diapause of C. septempunctata.

Fall armyworm, Spodoptera frugiperda (J. E. Smith, 1797), a crop pest native to tropical and subtropical regions of America, has invaded and spread into most regions in China, posing a severe threat to China's agriculture. The cold hardiness directly determines its geographic distribution through adapting to winter temperatures of different regions. Here, we measured supercooling points and lethal time (LT) at low temperatures of S. frugiperda. The supercooling points for developmental stages in increasing order were: adults (−15.05°C)

An experimental study was carried out to investigate the flame propagation and thermal hazard of the premixed N2O/fuel mixtures, including NH3, C3H8 and C2H4. The study provided the high speed video images and data about the flame locations, propagation patterns, overpressures and the quenching diameters during the course of combustion in different channels to elucidate the dynamics of various combustion processes. The onset decomposition temperature was determined using high-performance adiabatic calorimetry. It was shown that the order of the flame acceleration rate and thermal hazard was N2O/C2H4>N2O/C3H8>N2O/NH3.

The ladybird Coccinella septempunctata L., a predatory insect, serves as an excellent biological control agent against common agricultural pests. It undergoes a diapause phenomenon, during which a large amount of fat accumulates in the abdomen. A comprehensive analysis of this lipid accumulation can reveal the molecular mechanisms underlying diapause regulation, which can be exploited to improve the shipping and transport of the insect for agricultural applications. In this study, we compared the transcriptome of C. septempunctata during non-diapause, diapause, and post-diapause and screened four key genes related to lipid metabolism. The cDNA of these four relevant enzymes, acetyl-CoA carboxylase (ACC), long-chain fatty acid-CoA ligase (ACSL), elongase of very-long-chain fatty acids (ELO), and very-long-chain 3-oxoacyl-CoA reductase (KAR), were cloned using reverse transcription-polymerase chain reaction and rapid amplification of cDNA ends. Their expression profiles were analyzed during the preparation and maintenance phases of diapause and the post-diapause phase. The functions of these four key enzymes in diapause were further verified using RNA interference. All four genes were most closely related to the homeotic gene from Tribolium castaneum. The expression profiles of these four genes were significantly affected under diapause-inducing conditions; their expression level was the highest in the diapause preparation phase, and it gradually decreased with the diapause induction time. RNA interference showed that the target genes play important roles in fat storage during early diapause, and the decrease in their expression leads to a decrease in lipid content in C. septempunctata. These results indicate an important role of ACC, ACSL, ELO, and KAR in lipid accumulation. Our findings could help elucidate the production and accumulation of lipids by insects during the preparation for diapause and improve biological control.

Objective: This large-scale cross-sectional study aims to identify the characteristics of and risk factors associated with sexual repression among internal migrants in China. Methods: Between August 2013 and August 2015, a total of 8,669 internal migrants from four major cities in China (Beijing, Shanghai, Chengdu, and Chongqing) voluntarily participated in our study. They were interviewed, and the data on their demographic information, occupation, and sexual activities were collected. The Chi-square test and multiple logistic regressions were conducted to identify significant associations. A stepwise method was adopted for the selection of variables. Results: There were 3,597 (41.49%) males and 5,072 (58.51%) females in total. A higher percentage of males reported that they felt sexual repression compared to females (14.43% vs. 9.21%). After adjusting for other covariates, the consequence was showed that male migrants working for more than 5 days were more likely to report sexual repression (odds ratio [OR] = 1.40, P < 0.05). Living in a collective dormitory with others was also a risk factor for male migrants. The longer males spent with their partners, the less sexual repression occurred (OR= 0.94, P < 0.05). Similarly, agricultural household registration status and working for more than 5 days increased the risk for sexual repression among female migrants (OR= 1.41 and OR = 1.46, respectively, P < 0.05). Frequent and constructive communication also protected females against sexual repression (P < 0.05). Well-educated females experienced relatively less sexual repression when compared to their counterparts with less education (P < 0.05). Conclusions: Sexual repression was significantly associated with a few demographic, occupational, and sexual risk factors. Meaningful differences have been identified between male and female migrants. More effective intervention programs such as safeguard measures and welfare policies should be designed and implemented for a majority of female migrants and for those with agricultural household registration status.

Lack of the zona pellucida (ZP) is one of the manifestations of an oocyte maturation disorder. In recent years, genetic factors have attracted much attention as a possible cause of ZP anomalies. In this study, we report a form of primary infertility characterized by abnormal eggs that lack the ZP, which resulted from a compound heterozygous autosomal recessive mutation in ZP1. This compound heterozygous mutation has been reported for the first time, and our results may expand the spectrum of known mutations in ZP genes and provide evidence of oocyte maturation disorders during genetic counseling.

Aphidius gifuensis Ashmead (Hymenoptera: Aphidiidae) is a solitary endoparasitoid used in the biological control of various aphids. Diapause plays an important role in the successful production and deployment of A. gifuensis. Diapause can effectively extend the shelf life of biological control agents and solve several practical production problems like long production cycles, short retention periods, and discontinuities between supply and demand. In recent years, studies have been conducted on the environmental regulation and physiological and biochemical mechanisms of diapause in A. gifuensis. Nevertheless, the molecular mechanism of diapause in this species remains unclear. In this study, we compared the transcriptomes and proteomes of diapause and non-diapause A. gifuensis to identify the genes and proteins associated with this process. A total of 557 transcripts and 568 proteins were differentially expressed between the two groups. Among them, (1) genes involved in trehalose synthesis such as glycogen synthase, glycogen phosphorylase, and trehalose 6-phosphate synthase were upregulated in diapause at mRNA or protein level while glycolysis and gluconeogenesis-related genes were downregulated, suggesting that A. gifuensis stores trehalose as an energy resource and cryoprotectant; (2) the expression of immune-related genes like C-type lectins, hemocyanin, and phenoloxidase was increased, which helps to maintain immunity during diapause; (3) a chitin synthase and several cuticular protein genes were upregulated to harden the cuticle of diapausing A. gifuensis larval. These findings improve our understanding of A. gifuensis. diapause and provide the foundation for further pertinent studies.

Paprika was soaked in n-hexane to extract paprika pigment by using ultrasonic and microwave assisted extraction (UMAE). The effects of different operating variables were investigated and the extraction condition was optimized through orthogonal design: ultrasonic power of 50 w, microwave power of 240 w, powder-solvent ratio of 1: 25 (g/mL), microwave time of 600 s, paprika particle size of 60 mesh. At these conditions, the color value of 147 of paprika pigment was reached. Compared with the conventional water bath extraction method, UMAE has the advantages of shorter extraction time and higher efficiency, which may be related to the effect of UMAE on destroying the cellular structure of paprika.

Antibody–drug conjugates (ADCs), constructed with monoclonal antibodies (mAbs), linkers, and natural cytotoxins, are innovative drugs developed for oncotherapy. Owing to the distinctive advantages of both chemotherapy drugs and antibody drugs, ADCs have obtained enormous success during the past several years. The development of highly specific antibodies, novel marine toxins’ applications, and innovative linker technologies all accelerate the rapid R&D of ADCs. Meanwhile, some challenges remain to be solved for future ADCs. For instance, varieties of site-specific conjugation have been proposed for solving the inhomogeneity of DARs (Drug Antibody Ratios). In this review, the usages of various natural toxins, especially marine cytotoxins, and the development strategies for ADCs in the past decade are summarized. Representative ADCs with marine cytotoxins in the pipeline are introduced and characterized with their new features, while perspective comments for future ADCs are proposed.