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Objective Rare study of the non-coding and regulatory regions of the genome limits our ability to decode the mechanisms of fatty liver hemorrhage syndrome (FLHS) in chickens. Methods Herein, we constructed the high-fat diet-induced FLHS chicken model to investigate the genome-wide active enhancers and transcriptome by H3K27ac target chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-Seq) profiles of normal and FLHS liver tissues. Concurrently, an integrative analysis combining ChIP-seq with RNA-Seq and a comparative analysis with chicken FLHS, rat non-alcoholic fatty liver disease (NAFLD) and human NAFLD at the transcriptome level revealed the enhancer and super enhancer target genes and conservative genes involved in metabolic processes. Results In total, 56 and 199 peak-genes were identified in upregulated peak-genes positively regulated by H3K27ac (Cor (peak-gene correlation) ≥0.5 and log2(FoldChange) ≥1) (PP) and downregulated peak-genes positively regulated by H3K27ac (Cor (peak-gene correlation) ≥0.5 and log2(FoldChange)≤−1) (PN), respectively; then we screened key regulatory targets mainly distributing in lipid metabolism (PCK1, APOA4, APOA1, INHBE) and apoptosis (KIT, NTRK2) together with MAPK and PPAR signaling pathway in FLHS. Intriguingly, PCK1 was also significantly covered in up-regulated super-enhancers (SEs), which further implied the vital role of PCK1 during the development of FLHS. Conclusion Together, our studies have identified potential therapeutic biomarkers of PCK1 and elucidated novel insights into the pathogenesis of FLHS, especially for the epigenetic perspective.

N-glycosylation can have a profound effect on the quality of mAb therapeutics. In biomanufacturing, one of the ways to influence N-glycosylation patterns is by altering the media used to grow mAb cell expression systems. Here, we explore the potential of machine learning (ML) to forecast the abundances of N-glycan types based on variables related to the growth media. The ML models exploit a dataset consisting of detailed glycomic characterisation of Anti-HER fed-batch bioreactor cell cultures measured daily under 12 different culture conditions, such as changes in levels of dissolved oxygen, pH, temperature, and the use of two different commercially available media. By performing spent media quantitation and subsequent calculation of pseudo cell consumption rates (termed media markers) as inputs to the ML model, we were able to demonstrate a small subset of media markers (18 selected out of 167 mass spectrometry peaks) in a Chinese Hamster Ovary (CHO) cell cultures are important to model N-glycan relative abundances (Regression - correlations between 0.80–0.92; Classification - AUC between 75.0–97.2). The performances suggest the ML models can infer N-glycan critical quality attributes from extracellular media as a proxy. Given its accuracy, we envisage its potential applications in biomaufactucuring, especially in areas of process development, downstream and upstream bioprocessing.

Abstract Antibody–drug conjugates (ADC) payloads are cleavable drugs that act as the warhead to exert an ADC’s cytotoxic effects on cancer cells intracellularly. A simple and highly sensitive workflow is developed and validated for the simultaneous quantification of six ADC payloads, namely SN-38, MTX, DXd, MMAE, MMAF and Calicheamicin (CM). The workflow consists of a short and simple sample extraction using a methanol-ethanol mixture, followed by a fast liquid chromatography tandem mass spectrometry (LC–MS/MS) analysis. The results showed that well-validated linear response ranges of 0.4–100 nM for SN38, MTX and DXd, 0.04–100 nM for MMAE and MMAF, 0.4–1000 nM for CM were achieved in mouse serum. Recoveries for all six payloads at three different concentrations (low, medium and high) were more than 85%. An ultra-low sample volume of only 5 µL of serum is required due to the high sensitivity of the method. This validated method was successfully applied to a pharmacokinetic study to quantify MMAE in mouse serum samples.

Abstract Interstitial fluid (ISF), a biological fluid rich in diverse biomarkers and analytes and similar to blood composition, has garnered significant attention as a valuable source of clinically relevant information. Consequently, ISF-based wearable biosensors are emerging as powerful tools for non-invasive and minimally invasive disease diagnosis, personalized medicine, and other healthcare and biomedical applications. This review provides a comprehensive overview of recent advancements in ISF-based biosensors, with a particular focus on wearable ISF sensors. We first offer insights into ISF biomarkers and sampling techniques and discuss recent ISF sensing strategies that encompass materials, fabrication methods, and sensing mechanisms. Then, we present a comprehensive overview of their applications. Finally, we address the challenges faced in this field and offer a forward-looking perspective on promising future directions.

Walnut is an important economic tree species that is susceptible to osmotic stress. Scientific cultivation management is an important way to improve the yield and quality of walnuts, which requires understanding the regulatory mechanisms in response to osmotic stress. Therefore, in this study, 15 protein phosphatase 2A (PP2A) genes were identified from the walnut transcriptome (named JrPP2A01~15) and their potential function responses to osmotic stress were elucidated. The open reading frame (ORF) of JrPP2A01~15 ranges from 651 to 1,764 bp in length, the molecular weight of the encoded proteins are 24.15−65.61 kDa, and the theoretical isoelectric points are 4.80−8.37. These JrPP2As were unevenly distributed on 10 chromosomes and divided into five groups based on the composition of conserved domains, motifs, and exon/intron organizations. The five groups are JrPP2AAs, JrPP2AB's, JrPP2AB''s, JrPP2AB55s, and JrPP2ACs, including 1, 5, 2, 3, and 4 members, accordingly. The cis-elements in JrPP2As' promoters were involved in responses to hormone and abiotic stress. Most JrPP2A genes, excluding JrPP2A01, JrPP2A02, JrPP2A05, JrPP2A06, and JrPP2A13, could be induced significantly by PEG6000, NaCl, CaCl2 and ABA. JrPP2A02, JrPP2A05, JrPP2A07, JrPP2A09, and JrPP2A14, could independently interact with a bZIP transcription factor JrVIP1. Moreover, overexpression of JrPP2A07, JrPP2A09, and JrPP2A14 could significantly decrease ROS accumulation while increasing calcium (Ca) uptake exposed to PEG6000 and NaCl stresses, which was mediated by exogenous CaCl2 and ABA. These results suggested that JrPP2A genes play potential key roles in walnut response to drought and salt-inducing osmotic stress involving Ca- and ABA-dependent signaling pathways.

Aromaticity, in general, can promote a given reaction by stabilizing a transition state or a product via a mobility of π electrons in a cyclic structure. Similarly, such a promotion could be also achieved by destabilizing an antiaromatic reactant. However, both aromaticity and transition states cannot be directly measured in experiment. Thus, computational chemistry has been becoming a key tool to understand the aromaticity-driven reaction mechanisms. In this review, we will analyze the relationship between aromaticity and reaction mechanism to highlight the importance of density functional theory calculations and present it according to an approach via either aromatizing a transition state/product or destabilizing a reactant by antiaromaticity. Specifically, we will start with a particularly challenging example of dinitrogen activation followed by other small-molecule activation, CF bond activation, rearrangement, as well as metathesis reactions. In addition, antiaromaticity-promoted dihydrogen activation, CO2 capture, and oxygen reduction reactions will be also briefly discussed. Finally, caution must be cast as the magnitude of the aromaticity in the transition states is not particularly high in most cases. Thus, a proof of an adequate electron delocalization rather than a complete ring current is recommended to support the relatively weak aromaticity in these transition states.

Abstract Background Accumulating observational studies have identified associations between type 1 diabetes (T1D) and polycystic ovary syndrome (PCOS). Still, the evidence about the causal effect of this association is uncertain. Methods We performed a two-sample Mendelian randomization (MR) analysis to test for the causal association between T1D and PCOS using data from a large-scale biopsy-confirmed genome-wide association study (GWAS) in European ancestries. We innovatively divided T1D into nine subgroups to be analyzed separately, including: type1 diabetes wide definition, type1 diabetes early onset, type 1 diabetes with coma, type 1 diabetes with ketoacidosis, type 1 diabetes with neurological complications, type 1 diabetes with ophthalmic complications, type 1 diabetes with peripheral circulatory complications, type 1 diabetes with renal complications, and type 1 diabetes with other specified/multiple/unspecified complications. GWAS data for PCOS were obtained from a large-scale GWAS (10,074 cases and 103,164 controls) for primary analysis and the IEU consortium for replication and meta-analysis. Sensitivity analyses were conducted to evaluate heterogeneity and pleiotropy. Results Following rigorous instrument selection steps, the number of SNPs finally used for T1D nine subgroups varying from 6 to 36 was retained in MR estimation. However, we did not observe evidence of causal association between type 1 diabetes nine subgroups and PCOS using the IVW analysis, MR-Egger regression, and weighted median approaches, and all P values were > 0.05 with ORs near 1. Subsequent replicates and meta-analyses also yielded consistent results. A number of sensitivity analyses also did not reveal heterogeneity and pleiotropy, including Cochran’s Q test, MR-Egger intercept test, MR-PRESSO global test, leave-one-out analysis, and funnel plot analysis. Conclusion This is the first MR study to investigate the causal relationship between type 1 diabetes and PCOS. Our findings failed to find substantial causal effect of type 1 diabetes on risk of PCOS. Further randomized controlled studies and MR studies are necessary.

2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane (CL-20) is one of the high-energy oxidants, but has limited application due to its high sensitivity. In this work, polyvinylidene fluoride (PVDF) was used as a co-oxidizer, which is expected to increase the safety of CL-20. One kind of novel graphene-based carbohydrazide complex (GCCo and GCNi) was employed to modify the properties of dual-oxidant CL-20@PVDF composites by the spray drying method and compared with traditional nanocarbon materials (CNTs and GO). The properties of these composites were investigated using the TGA/DSC technique and impact test. The results show that GCCo and GCNi could increase the activation energy (Ea) of CL-20@PVDF composites, and change the physical model of CL-20@PVDF, which followed the random chain scission model and then the first-order reaction model. In addition, these nanocarbon materials could reduce the impact sensitivity of CL-20@PVDF by their unique structure. Besides that, a dual-oxidant CL-20@PVDF system was used to improve the combustion property of Boron. GCCo and GCNi with the synergetic effect could increase the flame temperature and control the burn rate of CL-20@PVDF@B compared with CNTs and GO. The energetic nanocarbon catalyst-modified oxidant provides a facile method for stabilizing high-energy but sensitive materials to broaden their application.

Abstract Background This study aimed to evaluate the predictive value of the initial screening characteristics of women with anovulatory polycystic ovary syndrome (PCOS) who did or did not respond to 2.5 mg letrozole (LET). Methods The clinical and laboratory characteristics of women with PCOS who underwent LET treatment were evaluated. Women with PCOS were stratified according to their responses to LET (2.5 mg). The potential predictors of their responses to LET were estimated using logistic regression analysis. Results Our retrospective study included 214 eligible patients with a response to 2.5 mg LET (n = 131) or no response to 2.5 mg LET (n = 83). PCOS patients who responded to 2.5 mg LET showed better outcomes than those who did not (2.5 mg LET) for pregnancy rate, live birth rate, pregnancy rate per patient, and live birth rate per patient. Logistic regression analyses showed that late menarche (odds ratio [OR], 1.79 [95% confidence intervals (CI), 1.22–2.64], P = 0.003), and increased anti-müllerian hormone (AMH) (OR, 1.12 [95% CI, 1.02–1.23], P = 0.02), baseline luteinizing hormone (LH)/ follicle stimulating hormone (FSH) (OR, 3.73 [95% CI, 2.12–6.64], P

Abstract Background To assess the correlation between clinical and biochemical hyperandrogenism parameters in polycystic ovary syndrome (PCOS) according to age. Methods This prospective study included 256 PCOS patients diagnosed according to the Rotterdam criteria in a university-based hospital. Androgen levels were measured using liquid chromatography-tandem mass spectrometry. Hirsutism, acne, and alopecia were assessed using the modified Ferriman-Gallwey (mF-G) score, Comprehensive Acne Severity Scale (CASS), and the Ludwig scale, respectively. The correlation between biochemical and clinical hyperandrogenism parameters was assessed in younger and older women with PCOS. Results The 256 PCOS patients were classified by age into two groups: age 18–29 years (n = 151) and age 30–40 years (n = 84). In women with PCOS, mF-G was significantly positively correlated with the free androgen index (FAI), dehydroepiandrosterone (DHEA), and DHEA sulfate (DHEA-S). CASS had a significant positive correlation with DHEA. mF-G was positively correlated with FAI in those aged 18–29 years, but the correlations were not significant in those aged 30–40 years. The positive correlation between specific body regions of clinical hyperandrogenism, especially mF-G of chin, lower abdomen, and thighs, and testosterone, as well as with FAI, was highest in those aged 18–29 years. In those aged 30–40 years clinical hyperandrogenism was mainly affected by DHEA, DHEA-S, and dihydrotestosterone. Conclusion The correlation between biochemical and clinical hyperandrogenism parameters varied with age in our East Asian population. Clinical hyperandrogenism was positively correlated with FAI in younger women with PCOS. The correlation between biochemical and clinical hyperandrogenism was not significant in older women with PCOS.

Abstract Polycystic ovary syndrome (PCOS) is a prevalent reproductive endocrine disorder, with metabolic abnormalities and ovulation disorders. The post‐translational modifications (PTMs) are functionally relevant and strengthen the link between metabolism and cellular functions. Lysine crotonylation is a newly identified PTM, the function of which in PCOS has not yet been reported. To explore the molecular mechanisms of crotonylation involved in the abnormalities of metabolic homeostasis and oocyte maturation in PCOS, by using liquid chromatography‐tandem mass spectrometry analysis, we constructed a comprehensive map of crotonylation modifications in ovarian tissue of PCOS‐like mouse model established by dehydroepiandrosterone induction. The crotonylation levels of proteins involved in metabolic processes were significantly decreased in PCOS ovaries compared to control samples. Further investigation showed that decrotonylation of Lon protease 1 (LONP1) at lysine 390 was associated with mitochondrial dysfunction in PCOS. Moreover, LONP1 crotonylation levels in PCOS were correlated with ovarian tissue oxidative stress levels, androgen levels, and oocyte development. Consistently, down‐regulation of LONP1 and LONP1 crotonylation levels were also observed in the blood samples of PCOS patients. Collectively, our study revealed a mechanism by which the decrotonylation of LONP1 may attenuate its activity and alter follicular microenvironment to affect oocyte maturation in PCOS.

Abstract Chronic diseases are currently posing a major challenge not only to our life expectancy and healthspan but also to the healthcare system, as patients will need continual monitoring, treatment, and care to mitigate some of the severe health complications that may arise. Merely frequent visits to medical facilities and clinics may not be sufficient. Home‐based point‐of‐care diagnosis and monitoring may be needed for the prevention and/or management of long‐term complications. Recent advances in materials, fabrication methods, and bioelectronics have led to some epidermal systems that can measure critical physiological parameters and provide long‐term monitoring of several chronic diseases. In this review, it is systematically outlined the progress of epidermal bioelectronics aimed at managing common chronic diseases, such as cardiovascular diseases, diabetes, and chronic wounds. Flexible and stretchable materials with related engineering approaches that render wearability are also discussed. Finally, a list of current challenges, future perspectives as well as potential research directions with the aim towards better translation in bringing these wearable technologies from the laboratory to the clinic and market are presented.

Most plants belonging to the widely distributed genus Dianthus are used for gardening. Interspecific hybridization of different Dianthus species leads to blurred genetic backgrounds. To obtain more genomic resources and understand the phylogenetic relationships among Dianthus species, the chloroplast genomes of 12 Dianthus species, including nine Dianthus gratianopolitanus varieties, were analyzed. The chloroplast genomes of these 12 species exhibited similar sizes (149,474–149,735 bp), with Dianthus caryophyllus having a chloroplast genome size of 149,604 bp marked by a significant contraction in inverted repeats. In the chloroplast genome of Dianthus, we identified 124–126 annotated genes, including 83–84 protein-coding genes. Notably, D. caryophyllus had 83 protein-coding genes but lacked rpl2. The repeat sequences of the chloroplast genome were consistent among species, and variations in the sequence were limited and not prominent. However, notable gene replacements were observed in the boundary region. Phylogenetic analysis of Dianthus indicated that D. caryophyllus and D. gratianopolitanus were most closely related, suggesting that the degree of variation within nine Dianthus varieties was no less than the variation observed between species. These differences provide a theoretical foundation for a more comprehensive understanding of the diversity within Dianthus species.

Graphene-based carbohydrazide coordination polymers are beneficial for improving solid propellants’ energy level and safety, so the study of their thermal decomposition mechanism is promoted for their wide application. In this paper, graphene oxide (GO) intercalated transition metal (Cu2+, Co2+, and Ni2+) complexes of carbohydrazide (CHZ) have been evaluated by using DSC/TGA apparatus and the TG-FTIR technique. Both isoconversional and combined kinetic methods were employed to calculate the kinetic parameters. The components inside GOCHZ-M would react with each other to cause a large mass loss rate and lead to a larger heat-releasing value than pure GO. The types of metal ions could affect their reaction model. Compared with GO, G-CHZ-Co shows a two-sided effect (stabilization and catalytic) on its decomposition. For G-CHZ-Co, the reaction model of each peak is close to the random 2d nucleation and nucleus growth model.

Abstract Walnut (Juglans regia L.) is an important woody oil plant and will be affected by abiotic and biological stress during its growth and development. The WD‐repeat (WD40) protein is widely involved in plant growth, development, metabolism, and abiotic stress response. To explore the stress response mechanism of walnut, based on the complete sequencing results of the walnut genome, this study identified and analyzed the physiological, biochemical, genetic structure, and conservative protein motifs of 42 JrWD40 genes, whose expression to abnormal temperature were tested to predict the potential biological function. The results showed that the open reading frame (ORF) of theseWD40 genes were 807–2,460 bp, encoding peptides were 29,610.55–90,387.98 Da covering 268–819 amino acids, as well as 12–112 phosphorylation sites. JrWD40 proteins were highly conserved with four to five WD40 domains and shared certain similarity to WD40 proteins from Arabidopsis thaliana (L.) Heynh. JrWD40 genes can be induced to varying degrees by low and high temperature treatments. JrWD40‐32, JrWD40‐27, JrWD40‐35, and JrWD40‐21 are affected by high temperature more seriously and their expression levels are higher; while JrWD40‐37, JrWD40‐26, JrWD40‐20, JrWD40‐24, and other genes are inhibited under low temperature stress. JrWD40‐40, JrWD40‐28, and JrWD40‐18 were first suppressed with low expression, while as the treatment time prolonging, the expression level was increased under cold condition. JrWD40‐14, JrWD40‐18, JrWD40‐34, and JrWD40‐3 displayed strong transcriptions response to both heat and cold stress. These results indicated that JrWD40 genes can participate in walnut adaptation to adversity and can be used as important candidates for walnut resistance molecular breeding.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of systemic autoimmune diseases, which is typified by inflammatory necrosis predominantly affecting the small vessels and often accompanied by positive ANCA. Clinically, AAV primarily includes microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA), and eosinophilic granulomatosis with polyangiitis (EGPA). It has been found that in AAV pathogenesis, both innate and adaptive immunity are related to neutrophil function mutually. Many proteins, such as myeloperoxidase (MPO) and proteinase 3 (PR3), in neutrophil cytoplasm lead to the production of proteins such as MPO-ANCA and PR3-ANCA by activating adaptive immunity. In addition, through the process of neutrophil extracellular trap (NET) formation, activation of an alternative complement pathway and the respiratory burst can stimulate the neutrophils close to vascular endothelial cells and will participate the vessel inflammation. This review aims to reveal the potential mechanisms regulating the association between the neutrophils and various types of AAVs and to emphasize the results of recent findings on these interactions. Moreover, multiple underlying signaling pathways involved in the regulation of neutrophils during AAV processes have also been discussed. The ultimate goal of this review is to identify novel biomarkers and therapeutic targets for AAV management in the future.

Abstract Background CIMP (CpG island methylator phenotype) is an epigenetic molecular subtype, observed in multiple malignancies and associated with the epigenetic silencing of tumor suppressors. Currently, for most cancers including gastric cancer (GC), mechanisms underlying CIMP remain poorly understood. We sought to discover molecular contributors to CIMP in GC, by performing global DNA methylation, gene expression, and proteomics profiling across 14 gastric cell lines, followed by similar integrative analysis in 50 GC cell lines and 467 primary GCs. Results We identify the cystathionine beta-synthase enzyme (CBS) as a highly recurrent target of epigenetic silencing in CIMP GC. Likewise, we show that CBS epimutations are significantly associated with CIMP in various other cancers, occurring even in premalignant gastroesophageal conditions and longitudinally linked to clinical persistence. Of note, CRISPR deletion of CBS in normal gastric epithelial cells induces widespread DNA methylation changes that overlap with primary GC CIMP patterns. Reflecting its metabolic role as a gatekeeper interlinking the methionine and homocysteine cycles, CBS loss in vitro also causes reductions in the anti-inflammatory gasotransmitter hydrogen sulfide (H2S), with concomitant increase in NF-κB activity. In a murine genetic model of CBS deficiency, preliminary data indicate upregulated immune-mediated transcriptional signatures in the stomach. Conclusions Our results implicate CBS as a bi-faceted modifier of aberrant DNA methylation and inflammation in GC and highlights H2S donors as a potential new therapy for CBS-silenced lesions.

Abstract Background The compromised gut microbiome that results from C-section birth has been hypothesized as a risk factor for the development of non-communicable diseases (NCD). In a double-blind randomized controlled study, 153 infants born by elective C-section received an infant formula supplemented with either synbiotic, prebiotics, or unsupplemented from birth until 4 months old. Vaginally born infants were included as a reference group. Stool samples were collected from day 3 till week 22. Multi-omics were deployed to investigate the impact of mode of delivery and nutrition on the development of the infant gut microbiome, and uncover putative biological mechanisms underlying the role of a compromised microbiome as a risk factor for NCD. Results As early as day 3, infants born vaginally presented a hypoxic and acidic gut environment characterized by an enrichment of strict anaerobes (Bifidobacteriaceae). Infants born by C-section presented the hallmark of a compromised microbiome driven by an enrichment of Enterobacteriaceae. This was associated with meta-omics signatures characteristic of a microbiome adapted to a more oxygen-rich gut environment, enriched with genes associated with reactive oxygen species metabolism and lipopolysaccharide biosynthesis, and depleted in genes involved in the metabolism of milk carbohydrates. The synbiotic formula modulated expression of microbial genes involved in (oligo)saccharide metabolism, which emulates the eco-physiological gut environment observed in vaginally born infants. The resulting hypoxic and acidic milieu prevented the establishment of a compromised microbiome. Conclusions This study deciphers the putative functional hallmarks of a compromised microbiome acquired during C-section birth, and the impact of nutrition that may counteract disturbed microbiome development. Trial registration The study was registered in the Dutch Trial Register (Number: 2838 ) on 4th April 2011.

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Emerging evidence suggests that prenatal exposure to ambient SO2 or NO2 induces fetal brain-damage. However, effects of prenatal exposure to SO2 or NO2 on toddler neurodevelopment and the effect-modification by ambient temperature remain unclear. Therefore, a prospective birth-cohort study was conducted from 2010 to 2012 in Shanghai, and 225 mother-child pairs were followed-up from mid-to-late pregnancy until 24–36 months postpartum. During the whole pregnancy, daily SO2/NO2 and temperature levels were obtained for each woman. Gesell-Development-Schedule was used to assess toddler neurodevelopment in the domains of gross-motor, fine-motor, adaptive-behavior, language and social-behavior. Distributed-lag-nonlinear-models simultaneously accounting for exposure-response and lag-response associations were applied to assess the impacts of prenatal SO2/NO2 exposure on neurodevelopment. Each 10-μg/m3 increase in weekly average SO2 concentrations had adverse associations with gross-motor in gestational-weeks 1–6, with adaptive-behavior in weeks 26–30, and with language in weeks 30–36 (developmental-quotient changes: − 1.17% to − 0.12%, P-values

Juglans regia is a world-famous woody oil plant, whose yield and quality are affected by drought stress. Ethylene-responsive factors (ERFs) play vital role in plant stress response. In current study, to comprehend the walnut molecular mechanism of drought stress response, an ERF transcription factor was clarified from J. regia (JrERF2–2) and its potential function mechanism to drought was clarified. The results showed that JrERF2–2 could be induced significantly by drought. The transgenic Arabidopsis over-expression of JrERF2–2 displayed enhanced growth, antioxidant enzyme vitalities, reactive oxygen species scavenging and proline produce under drought stress. Especial the glutathione-S-transferase (GST) activity and most GST genes’ transcription were elevated obviously. Yeast one-hybrid (Y1H) and co-transient expression (CTE) methods revealed that JrERF2–2 could recognize JrGST4, JrGST6, JrGST7, JrGST8, and JrGSTF8 by binding to GCC-box, and recognize JrGST11, JrGST12, and JrGSTN2 by binding to DRE motif. Meanwhile, the binding activity was strengthened by drought stress. Moreover, JrERF2–2 could interact with JrWRKY7 to promote plant drought tolerance; JrWRKY7 could also distinguish JrGST4, JrGST7, JrGST8, JrGST11, JrGST12, and JrGSTF8 via binding to W-Box motif. These results suggested that JrERF2–2 could effectively improve plant drought tolerance through interacting with JrWRKY7 to control the expression of GSTs. JrERF2–2 is a useful plant representative gene for drought response in molecular breeding.

Background Walnut is an important economic tree species with prominent economic value and ecological functions. However, in recent years, walnuts have become susceptible to drought stress, resulting in a decline in comprehensive benefits. Therefore, it is necessary to identify the regulatory molecular mechanism associated with walnut response to drought. In many plants, ethylene responsive factor (ERF) gene family plays important roles in response to biotic and abiotic stress, especial drought. Therefore, the identification and characterisation of walnut ERF genes will benefit walnut with regard to the clarification of drought response mechanism as well as the management, production, and quality of plantations. Methods ‘ERF’ was compared against the walnut transcriptome, and the JrERFs with a complete open reading frame (ORF) were identified by ORF Finder. The molecular weights, amino acid residues, and theoretical isoelectric point (pI) were predicted by ExPASy. The distribution of JrERFs in chromosome locations was determined based on walnut genome data from NCBI. The intron-exon structures and conserved domains were analysed using Gene Structure Display Server 2.0 and CD-Search, accordingly. Multi-sequence alignment and a phylogenetic tree were constructed by ClustalX2.1 and MEGA7, respectively. The conserved motifs were acquired using MEME. Total RNA was isolated using the cetyltrimethylammonium ammonium bromide (CTAB) method (Yang et al., 2018). Gene expression was determined by using real-time quantitative polymerase chain reaction (qRT-PCR) analysis and calculated according to the 2−ΔΔCT method (Livak & Schmittgen, 2001). Results A total of 44 JrERFs were identified from the walnut transcriptome, whose ORFs were 450–1,239 bp in length. The molecular weights of the JrERF proteins (consisting 149–412 amino acids) were 16.81–43.71 kDa, with pI ranging from 4.8 (JrERF11) to 9.89 (JrERF03). The JrERFs can be divided into six groups (B1–B6), and among the groups, B6 contained the most number of members. Each JrERF contained 1–6 motifs and each motif comprised 9–50 amino acids. Among the motifs, motif1, motif2, and motif3 were the most abundant. More than 40% of JrERFs were up-regulated continuously when subjected to ethephon (ETH), PEG6000, and PEG6000+ETH treatments. Of all the JrERFs, JrERF11 showed the highest expression. Therefore, we conclude that walnut ERF genes are highly conserved and involved in the regulation of drought response in the presence of ETH. JrERFs are possibly important candidate genes for molecular breeding; hence, the findings of this study provides the theoretical basis for further investigation of ERF genes in walnut and other species.

Abstract Polytetrafluoroethylene (PTFE) is a fascinating electret material widely used for energy harvesting and sensing, and an enhancement in the performance could be expected by reducing its size into nanoscale because of a higher surface charge density attained. Hence, the present study demonstrates the use of nanofibrous PTFE for high-performance self-powered wearable sensors. The nanofibrous PTFE is fabricated by electrospinning with a suspension of PTFE particles in dilute polyethylene oxide (PEO) aqueous solution, followed by a thermal treatment at 350 °C to remove the PEO component from the electrospun PTFE-PEO nanofibers. The obtained PTFE nanofibrous membrane exhibits good air permeability with pressure drop comparable to face masks, excellent mechanical property with tensile strength of 3.8 MPa, and stable surface potential of − 270 V. By simply sandwiching the PTFE nanofibrous membrane into two pieces of conducting carbon clothes, a breathable, flexible, and high-performance nanogenerator (NG) device with a peak power of 56.25 μW is constructed. Remarkably, this NG device can be directly used as a wearable self-powered sensor for detecting body motion and physiological signals. Small elbow joint bending of 30°, the rhythm of respiration, and typical cardiac cycle are clearly recorded by the output waveform of the NG device. This study demonstrates the use of electrospun PTFE nanofibrous membrane for the construction of high-performance self-powered wearable sensors.

Summary: B lymphocytes undergo metabolic reprogramming upon activation to meet the bioenergetic demands for proliferation and differentiation. Yet, little is known if and how the fate of naive B cells is metabolically regulated. Here, we specifically delete von Hippel-Lindau protein (VHL) in B cells using CD19-Cre and demonstrate that metabolic balance is essential for naive B cell survival. Loss of VHL disturbs glycolytic and oxidative metabolic balance and causes severe reduction in mature B cells. Mechanistically, the metabolic imbalance in VHL-deficient B cells, arising from over-stabilization of hypoxia-inducible factor-1α (HIF-1α), triggers reductive glutamine metabolism leading to increased Fas palmitoylation and caspase-8-mediated apoptosis. Blockade of reductive glutamine metabolic flux by lactate supplementation and ATP citrate lyase inhibition restores the metabolic balance and rectifies the impaired survival of VHL-deficient B cells. Hence, we unravel that the VHL/HIF-1α pathway is required to maintain the metabolic balance of naive B cells and ensure their survival. : Biological Sciences; Immunology; Cell Biology Subject Areas: Biological Sciences, Immunology, Cell Biology

Among deep learning methods, convolutional neural networks (CNNs) are able to extract features automatically and have increasingly been used in intelligent fault diagnosis studies. However, studies seldomly concentrate on the weakness associated with a highly imbalanced distribution of fault types due to different failure rates and when multiple faults are easily confused with single faults. To solve these problems, this paper developed a stochastic discrete-time series deep convolutional neural network (SDCNN) method based on random oversampling along with a progressive method with multiple SDCNNs to improve the diagnosis performance. To assess the developed method, datasets from three avionics 24-pulse auto-transformer rectifier units (ATRUs), which are secondary electric power supplies in aircraft, were analyzed and compared with other CNN methods.

Background. This study is aimed at investigating the repairing effect of mesenchymal stem cells and their exosomes from different sources on ovarian granulosa cells damaged by chemotherapy drugs—phosphoramide mustard (PM). Methods. In this study, we choose bone marrow mesenchymal stem cells (BMSCs) and human placental mesenchymal stem cells (HPMSCs) for research. Then, they were cocultured with human ovarian granulosa cells (SVOG) injured by phosphoramide mustard (PM), respectively. β-Galactosidase staining, flow cytometry, and Western blot were used to detect the changes in the senescence and apoptosis of SVOG cells before and after their coculture with the above two types of MSCs. Subsequently, exosomes from these two types of MSCs were extracted and added to the culture medium of SVOG cells after PM injury to test whether these two types of exosomes played a role similar to that of MSCs in repairing damaged SVOG cells. Results. PM treatment-induced apoptotic SVOG cells were significantly decreased after HPMSCs and BMSCs as compared with control group. After coculturing with these two types of MSCs, PM-treated SVOG cells showed significantly reduced senescence and apoptosis proportions as well as cleaved-Caspase 3 expression, and HPMSCs played a slightly stronger role than BMSCs in repairing SVOG cells in terms of the above three indicators. In addition, the ratios of senescent and apoptotic SVOG cells were also significantly reduced by the two types of exosomes, which played a role similar to that of MSCs in repairing cell damages. Conclusions. The results indicated that BMSCs, HPMSCs, and their exosomes all exerted a certain repair effect on SVOG cells damaged by PM, and consistent repair effect was observed between exosomes and MSCs. The repair effect of exosomes secreted from BMSCs and HPMSCs on the SVOG cells was studied for the first time, and the results fully demonstrated that exosomes are the key carriers for MSCs to play their role.

Niclosamide is an oral anthelmintic drug, approved for use against tapeworm infections. Recent studies suggest however that niclosamide may have broader clinical applications in cancers, spurring increased interest in the functions and mechanisms of niclosamide. Previously, we reported that niclosamide targets a metabolic vulnerability in p53-deficient tumours, providing a basis for patient stratification and personalised treatment strategies. In the present study, we functionally characterised the contribution of the aniline 4′-NO2 group on niclosamide to its cellular activities. We demonstrated that niclosamide induces genome-wide DNA damage that is mechanistically uncoupled from its antitumour effects mediated through mitochondrial uncoupling. Elimination of the nitro group in ND-Nic analogue significantly reduced γH2AX signals and DNA breaks while preserving its antitumour mechanism mediated through a calcium signalling pathway and arachidonic acid metabolism. Lipidomics profiling further revealed that ND-Nic-treated cells retained a metabolite profile characteristic of niclosamide-treated cells. Notably, quantitative scoring of drug sensitivity suggests that elimination of its nitro group enhanced the target selectivity of niclosamide against p53 deficiency. Importantly, the results also raise concern that niclosamide may impose a pleiotropic genotoxic effect, which limits its clinical efficacy and warrants further investigation into alternative drug analogues that may ameliorate any potential unwanted side effects.

Camellia oleifera is one of the four largest woody edible oil plants in the world with high ecological and medicinal values. Due to frequent interspecific hybridization, it was difficult to study its genetics and evolutionary history. This study used C. oleifera that was collected on Hainan Island to conduct our research. The unique island environment makes the quality of tea oil higher than that of other species grown in the mainland. Moreover, a long-term geographic isolation might affect gene structure. In order to better understand the molecular biology of this species, protect excellent germplasm resources, and promote the population genetics and phylogenetic studies of Camellia plants, high-throughput sequencing technology was used to obtain the chloroplast genome sequence of Hainan C. oleifera. The results showed that the whole chloroplast genome of C. oleifera in Hainan was 156,995 bp in length, with a typical quadripartite structure of a large single copy (LSC) region of 86,648 bp, a small single copy (SSC) region of 18,297 bp, and a pair of inverted repeats (IRs) of 26,025 bp. The whole genome encoded a total of 141 genes (115 different genes), including 88 protein-coding genes, 45 tRNA genes, and eight rRNA genes. Among these genes, nine genes contained one intron, two genes contained two introns, and four overlapping genes were also detected. The total GC content of Hainan C. oleifera’s chloroplast genome was 37.29%. The chloroplast genome structure characteristics of Hainan C. oleifera were compared with mainland C. oleifera and those of the other eight closely related Theaceae species; it was found that the contractions and expansions of the IR/LSC and IR/SSC regions affected the length of chloroplast genome. The chloroplast genome sequences of these Theaceae species were highly similar. A comparative analysis indicated that the Theaceae species were conserved in structure and evolution. A total of 51 simple sequence repeat (SSR) loci were detected in the chloroplast genome of Hainan C. oleifera, and all Camellia plants did not have pentanucleotide repeats, which could be used as a good marker in phylogenetic studies. We also detected seven long repeats, the base composition of all repeats was biased toward A/T, which was consistent with the codon bias. It was found that Hainan C. oleifera had a similar evolutionary relationship with C. crapnelliana, through the use of codons and phylogenetic analysis. This study can provide an effective genomic resource for the evolutionary history of Theaceae family.

Unfortunately, we had made some mistakes of the funding and the introduction of section organization in Section 1. These two mistakes had no influence on the discussion and conclusions in the paper. The correct funding and the introduction of chapter arrangement are given here.

Chloroplast genomes are widely used in genetic engineering, molecular marker development, and phylogeny. In order to analyze the complete chloroplast genome of Dianthus caryophyllus, the complete chloroplast genome of D. caryophyllus was sequenced and annotated. On the other hand, phylogenetic analysis of the chloroplast genome of D. caryophyllus was carried out. The results showed that the whole length of the chloroplast genome of D. caryophyllus was 147,604 bp, and had a typical conserved quadripartite structure. The G and C basic content of D. caryophyllus chloroplast was 36.3%. The genome contained 83 protein-coding genes, 34 tRNA genes, and 6 rRNA genes. Among the protein-coding genes, 10 genes contain a single intron and 2 genes contain two introns. The phylogeny of D. caryophyllus indicated that the closest phylogenetic relationship was D. longicalyxanus. This study provides materials for the molecular study of D. caryophyllus may improve the carnation industry.

A quantitative evaluation method has been developed to study the effects of nanoadditives on thermal decomposition mechanisms of energetic compounds using the conventional thermogravimetry coupled with mass spectrometry (TG/MS) technique. The decomposition of ammonium perchlorate (AP) under the effect of several energetic catalysts has been investigated as a demonstration. In particular, these catalysts are transition metal (Cu2+, Co2+ and Ni2+) complexes of triaminoguanidine (TAG), using graphene oxide (GO) as dopant. They have been well-compared in terms of their catalytic effects on the concentration of the released gaseous products of AP. These detailed quantitative analyses of the gaseous products of AP provide a proof that the proton transfer between ∙O and O2 determines the catalytic decomposition pathways, which largely depend on the type of reactive centers of the catalysts. This quantitative method could be applied to evaluate the catalytic effects of any other additives on the thermal decomposition of various energetic compounds.

Radiationless electromagnetic interference (REI) has been used to achieve focusing below Abbe’s diffraction limit. Here, we demonstrate an approach to REI that uses the Fano resonance of subwavelength slits to achieve subdiffraction focusing. Two main features of the Fano resonance are critical: (1) The Fano resonance suppresses radiation by destructive interference, thereby allowing for REI, and (2) the Fano resonance creates a resonant field enhancement allowing one to overcome evanescent decay, which is different from past approaches to REI. An analytic theory is introduced to explain these results. While the analytic theory is formulated for a perfect electric conductor, comprehensive numerical simulations show the applicability in the visible regime, where losses and plasmonic effects play a role.

Background: Robot-assisted laparoscopic cystectomy with intracorporeal urinary diversion (iRARC) is increasingly being used in recent years. Whether iRARC offers advantages over open radical cystectomy (ORC) remains controversial. This study aimed to compare the difference of perioperative outcomes, oncological outcomes and complications between iRARC and ORC. Methods: The PubMed, Embase, Cochrane Library, Web of Science and CNKI databases were searched in July 2023 according to the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses) statement. Studies were identified to be eligible if they compared perioperative outcomes, oncological outcomes and complications in patients who underwent iRARC with ORC. Results: Twenty-two studies involving 7020 patients were included. Compared to ORC, iRARC was superior for estimated blood loss [estimated blood loss (EBL) weighted mean difference (WMD): -555.52; 95% CI, -681.64 to -429.39; P<0.001], blood transfusion rate [odds ratio (OR): 0.16; 95% CI, 0.09-0.28; P<0.001], length of hospital stay [length of hospital stay (LOS) WMD: -2.05; 95% CI, -2.93 to -1.17; P<0.001], Clavien-Dindo grades =III complication rate [30 days: OR: 0.57; 95% CI 0.44-0.75; P<0.001; 90 days: OR: 0.71; 95% CI 0.60-0.84; P<0.001], and positive surgical margin [positive surgical margin (PSM) OR: 0.65; 95% CI 0.49-0.85; P=0.002]. However, iRARC had a longer operative time [operative time (OT) WMD: 68.54; 95% CI 47.41-89.67; P<0.001] and a higher rate of ureteroenteric stricture [ureteroenteric stricture (UES) OR: 1.56; 95%CI 1.16-2.11; P=0.003]. Time to flatus, time to bowel, time to regular diet, readmission rate, Clavien-Dindo grades less than III complication rate for iRARC were similar to that for ORC. Interestingly, the results of subgroup analysis revealed no difference in EBL between iRARC and ORC when the diversion type was neobladder. When the ileal conduit was selected as the diversion type, the LOS was similar in both procedures. Conclusion: Robot-assisted laparoscopic cystectomy with intracorporeal urinary diversion appears to be superior to open radical cystectomy in terms of effectiveness and safety. However, attention should be paid to the occurrence of ureteroenteric stricture during follow-up. [ABSTRACT FROM AUTHOR]

Aim: This study aims to establish an artificial intelligence model, ThyroidNet, to diagnose thyroid nodules using deep learning techniques accurately. Methods: A novel method, ThyroidNet, is introduced and evaluated based on deep learning for the localization and classification of thyroid nodules. First, we propose the multitask TransUnet, which combines the TransUnet encoder and decoder with multitask learning. Second, we propose the DualLoss function, tailored to the thyroid nodule localization and classification tasks. It balances the learning of the localization and classification tasks to help improve the model's generalization ability. Third, we introduce strategies for augmenting the data. Finally, we submit a novel deep learning model, ThyroidNet, to accurately detect thyroid nodules. Results: ThyroidNet was evaluated on private datasets and was comparable to other existing methods, including U-Net and TransUnet. Experimental results show that ThyroidNet outperformed these methods in localizing and classifying thyroid nodules. It achieved improved accuracy of 3.9% and 1.5%, respectively. Conclusion: ThyroidNet significantly improves the clinical diagnosis of thyroid nodules and supports medical image analysis tasks. Future research directions include optimization of the model structure, expansion of the dataset size, reduction of computational complexity and memory requirements, and exploration of additional applications of ThyroidNet in medical image analysis. [ABSTRACT FROM AUTHOR]