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Abstract Background Venoms have repeatedly evolved over 100 occasions throughout the animal tree of life, making them excellent systems for exploring convergent evolutionary novelty. Growing evidence supports that venom evolution is predominantly driven by prey or host-related selection pressures, and the expression patterns of venom glands reflect adaptive evolution. However, it remains elusive whether the evolution of expression patterns in venom glands is likewise a convergent evolution driven by their prey/host species. Results We utilized parasitoid wasps that had independently adapted to Drosophila hosts as models to investigate the convergent evolution of venom gland transcriptomes in 19 hymenopteran species spanning ~ 200 million years of evolution. Comparative transcriptome analysis reveals that the global expression patterns among the venom glands of Drosophila parasitoid wasps do not achieve higher similarity compared to non-Drosophila parasitoid wasps. Further evolutionary analyses of expression patterns at the single gene, orthogroup, and Gene Ontology (GO) term levels indicate that some orthogroups/GO terms show correlation with the Drosophila parasitoid wasps. However, these groups rarely include genes highly expressed in venom glands or putative venom genes in the Drosophila parasitoid wasps. Conclusions Our study suggests that convergent evolution may not play a predominant force shaping gene expression levels in the venom gland of the Drosophila parasitoid wasps, offering novel insights into the co-evolution between venom and prey/host.

Abstract Type 2 diabetes mellitus combined with metabolic dysfunction-associated steatotic liver disease (MASLD) leads to an increasing incidence of liver injury year by year, and patients are at a significantly higher risk of developing cirrhosis or even liver failure. No drugs have emerged to specifically treat this disease. The aim of this study is to investigate the mechanisms and causative hub genes of type 2 diabetes combined with MASLD. The data were obtained through the GEO platform for bioinformatics analysis and validated by in vitro experiments to find the causative targets of type 2 diabetes mellitus combined with MASLD, which will provide some theoretical basis for the development of future therapeutic drugs. GSE23343 and GSE49541 were downloaded from the Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs) in type 2 diabetes mellitus combined with MASLD for functional enrichment analysis. And STRING database and Cytoscape software were used to construct Protein–Protein Interaction (PPI) and hub gene networks. And GO (gene ontology, GO) analysis and KEGG (Kyoto encyclopedia of genes and genomes, KEGG) enrichment analysis were performed on target genes. A total of 185 co-expressed DEGs were obtained by differential analysis, and 20 key genes involved in the development and progression of type 2 diabetes were finally screened. These 20 key genes were involved in 529 GO enrichment results and 20 KEGG enrichment results, and were mainly associated with ECM–receptor interaction, Focal adhesion, Human papillomavirus infection, PI3K-Akt signaling pathway, and the Toll-like receptor signaling pathway. A total of two target genes (SPP1, collagen IV) were found to be highly correlated with type 2 diabetes mellitus combined with MASLD. Real time PCR results showed that there was a significant difference in SPP1 and collagen IV mRNA expression among the three groups (P

Abstract Pyroptosis, a novel type of programmed cell death (PCD), which provides a feasible therapeutic option for the treatment of tumors. However, due to the hypermethylation of the promoter, the critical protein Gasdermin E (GSDME) is lacking in the majority of cancer cells, which cannot start the pyroptosis process and leads to dissatisfactory therapeutic effects. Additionally, the quick clearance, systemic side effects, and low concentration at the tumor site of conventional pyroptosis reagents restrict their use in clinical cancer therapy. Here, we described a combination therapy that induces tumor cell pyroptosis via the use of ultrasound-targeted microbubble destruction (UTMD) in combination with DNA demethylation. The combined application of UTMD and hydralazine-loaded nanodroplets (HYD-NDs) can lead to the rapid release of HYD (a demethylation drug), which can cause the up-regulation of GSDME expression, and produce reactive oxygen species (ROS) by UTMD to cleave up-regulated GSDME, thereby inducing pyroptosis. HYD-NDs combined with ultrasound (US) group had the strongest tumor inhibition effect, and the tumor inhibition rate was 87.15% (HYD-NDs group: 51.41 ± 3.61%, NDs + US group: 32.73%±7.72%), indicating that the strategy had a more significant synergistic anti-tumor effect. In addition, as a new drug delivery carrier, HYD-NDs have great biosafety, tumor targeting, and ultrasound imaging performance. According to the results, the combined therapy reasonably regulated the process of tumor cell pyroptosis, which offered a new strategy for optimizing the therapy of GSDME-silenced solid tumors.

Background Impaired ventilatory efficiency during exercise is a predictor of mortality in chronic obstructive pulmonary disease. However, little is known about the clinical features and associated factors of impaired ventilatory efficiency in China.Methods We conducted a cross-sectional community-based study in China and collected demographic and clinical information, cardiopulmonary exercise testing, spirometry, and CT data. Impaired ventilatory efficiency was defined by a nadir ventilatory equivalent for CO2 production above the upper limit of normal. Multivariable linear and logistic regression models were used to explore the clinical features and associated factors of impaired ventilatory efficiency.Results The final analyses included 941 subjects, 702 (74.6%) of whom had normal ventilatory efficiency and 239 (25.4%) had impaired ventilatory efficiency. Participants with impaired ventilatory efficiency had more chronic respiratory symptoms, poorer lung function and exercise capacity, and more severe emphysema (natural logarithm transformation of the low-attenuation area of the lung with attenuation values below −950 Hounsfield units, logLAA−950: 0.19±0.65 vs −0.28±0.63, p

AbstractObjective We aim to explore the contributing factors of clinical pregnancy outcomes in PCOS patients undergoing their first FET treatment.Methods A retrospective analysis was conducted on 574 PCOS patients undergoing their first FET treatment at a private fertility center from January 2018 to December 2021.Results During the first FET cycle of PCOS patients, progesterone levels (aOR 0.109, 95% CI 0.018-0.670) and endometrial thickness (EMT) (aOR 1.126, 95% CI 1.043-1.419) on the hCG trigger day were associated with the clinical pregnancy rate. Similarly, progesterone levels (aOR 0.055, 95% CI 0.007-0.420) and EMT (aOR 1.179, 95% CI 1.011-1.376) on the hCG trigger day were associated with the live birth rate. In addition, AFC (aOR 1.179, 95% CI 1.011-1.376) was found to be a risk factor for preterm delivery.Conclusions In women with PCOS undergoing their first FET, lower progesterone levels and higher EMT on hCG trigger day were associated with clinical pregnancy and live birth, and AFC was a risk factor for preterm delivery. During FET treatment, paying attention to the patient’s endocrine indicators and follicle status may have a positive effect on predicting and improving the pregnancy outcome of PCOS patients.

Background There are limited data on the clinical features and longitudinal prognosis of variable obstruction, particularly among never smokers and different variable obstruction types. Therefore, we aimed to evaluate the clinical characteristics of the participants with variable obstruction and determine the relationship between variable obstruction and the development of chronic obstructive pulmonary disease (COPD) and the decline of lung function in a community-dwelling study of Chinese, especially among never smokers and different variable obstruction subtypes.Methods Participants with preserved spirometry (postbronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ≥0.70) at baseline from the Early COPD cohort were included in our analysis. Participants with variable obstruction (prebronchodilator FEV1/FVC

In this study, a new fermented food was developed using pineapple by-products and whey protein (2.6%) as raw materials through the co-fermentation of autochthonous lactic acid bacteria and yeast. To better understand the fermentation mechanism and the impact of microorganisms on the entire fermentation system, we tracked the changes in carbohydrate and amino acid profiles, organoleptic quality and microbial community during the fermentation process. Compared with unfermented samples, dietary fiber and free amino acids increased significantly as fermentation proceeded. The fermented samples were significantly lower in astringency and bitterness and significantly higher in sourness, umami and richness. The fermented products were richer in volatile compounds with floral, cheesy, fruity and other flavors. Relevant analyses showed that the core microbial community was highly correlated with the quality attributes of the fermented products. Microorganisms such as Lactococcus, Weissella, Hanseniaspora, Saccharomyces and Lachancea contributed significantly to the fermented products.

In this study, casein peptides were obtained by alcalase hydrolyzation and Lactobacilus fermentation to prepare the casein peptide-zinc chelates, which are a kind of efficient and well-absorbed zinc supplement. The structure of casein peptide-zinc chelates was characterized by spectroscopic instruments. The digestive stability and safety were also assayed using in vitro digestive model and Caco-2 cell experiment. The results indicated that the optimal conditions for preparing casein peptides were as follows: Volume of alcalase was 0.3% (w/v), pH of reaction system was 9.0, Lactobacilus fermentation time was 12 h. Under this condition, the peptide content was 142.39±0.95 mg/g, and the zinc chelation rate was 31.41%±0.97%. The chelation with zinc destroyed the structure of casein peptides leading to a loose surface structure. Spectroscopic analysis showed that Zn2+ can bind to the reactive groups on casein peptides, with the chelating sites being carboxyl oxygen, hydroxyl oxygen and amino groups. The results of in vitro digestion showed that casein peptide-zinc chelates possessed better solubility than that of zinc sulfate. After gastrointestinal digestion, the DPPH and ABTS+ scavenging ability of casein peptide-zinc chelates increased by 26.19%±3.30% and 71.96%±7.06%, respectively. However, the ferric ion reducing power of the casein peptide-zinc chelates decreased by 36.26%±2.80%. At the same time, the β-turn and random coil content of the casein peptide-zinc chelate decreases during digestion, the β-sheet structure increases and Zn2+ play a role in maintaining the peptide structure. Furthermore, the cytotoxicity test indicated that casein peptide-zinc chelates gastrointestinal digest were toxic to Caco-2 cells when the concentration exceeded 0.4 mg/mL. Finally, 15 and 13 dairy-derived peptides were identified from casein hydrolysate and casein peptide-zinc chelates, respectively, using mass spectrometry. These results will provide scientific evidence for the development and application of efficient casein peptide-zinc chelates.

BackgroundDuring aging, chronic inflammation can promote tumor development and metastasis. Patients with chronic inflammatory bowel diseases (IBD) are at an increased risk of developing colorectal cancer (CRC). However, the molecular mechanism underlying is still unclear.MethodsWe conducted a large-scale single-cell sequencing analysis comprising 432,314 single cells from 92 CRC and 24 IBD patients. The analysis focused on the heterogeneity and commonality of CRC and IBD with respect to immune cell landscape, cellular communication, aging and inflammatory response, and Meta programs.ResultsThe CRC and IBD had significantly different propensities in terms of cell proportions, differential genes and their functions, and cellular communication. The progression of CRC was mainly associated with epithelial cells, fibroblasts, and monocyte-macrophages, which displayed pronounced metabolic functions. In particular, monocyte-macrophages were enriched for the aging and inflammation-associated NF-κB pathway. And IBD was enriched in immune-related functions with B cells and T cells. Cellular communication analysis in CRC samples displayed an increase in MIF signaling from epithelial cells to T cells, and an increase in the efferent signal of senescence-associated SPP1 signaling from monocyte-macrophages. Notably, we also found some commonalities between CRC and IBD. The efferent and afferent signals showed that the pro-inflammatory cytokine played an important role. And the activity of aging and inflammatory response with AUCell analysis also showed a high degree of commonality. Furthermore, using the Meta programs (MPs) with the NMF algorithm, we found that the CRC non-malignant cells shared a substantial proportion of the MP genes with CRC malignant cells (68% overlap) and IBD epithelial cells (52% overlap), respectively. And it was extensively involved in functions of cell cycle and immune response, revealing its dual properties of inflammation and cancer. In addition, CRC malignant and non-malignant cells were enriched for the senescence-related cell cycle G2M phase transition and the p53 signaling pathway.ConclusionOur study highlights the characteristics of aging, inflammation and tumor in CRC and IBD at the single-cell level, and the dual property of inflammation-cancer in CRC non-malignant cells may provide a more up-to-date understanding of disease transformation.

Thus far, little is known about whether jackfruit flake, a byproduct of jackfruit, can be used as a fermentation substrate to obtain value-added products through microbial fermentation. Here, jackfruit flake puree was fermented by three different ways: spontaneous fermentation (JF), inoculated with LAB (JFL), inoculated co-fermentation with LAB and yeast (JFC). In contrast to JF, the total polyphenol and flavonoid content and syndrome-associated enzyme inhibition are significantly increased in JFC at the end of fermentation. Electronic tongue analysis revealed that the JFC was significantly lower in astringency and higher in bitterness. 41 volatile compounds were identified during fermentation by HS-SPME-GC–MS, and JFC was richer in honey, rose, and fruity flavors. A total of 290 compounds were screened for discriminative pre- and post-fermentation differential metabolites by non-target metabolomics analysis. These results provide a potential reference for the conversion of jackfruit waste into functional products using fermentation.

Summary: Insects are susceptible to elevated temperatures, resulting in impaired fertility, and shortened lifespan. This study investigated the genetic mechanisms underlying heat stress effects. We conducted RNA sequencing on Pteromalus puparum exposed to 25°C and 35°C, revealing transcriptional signatures. Weighted Gene Co-expression Network Analysis uncovered heat stress-associated modules, forming a regulatory network of 113 genes. The network is naturally divided into two subgroups, one linked to acute heat stress, including heat shock proteins (HSPs), and the other to chronic heat stress, involving lipogenesis genes. We identified an Xap5 Heat Shock Regulator (XHSR) gene as a crucial network component, validated through RNA interference and quantitative PCR assays. XHSR knockdown reduced wasps’ lifespan while directly inducing HSPs and mediating lipogenesis gene induction. CRISPR/Cas9-mediated knockout of the Drosophila XHSR homolog reduced mutants’ survival, highlighting its conserved role. This research sheds light on thermal tolerance mechanisms, offering potential applications in pest control amid global warming.

Abstract Despite rapid advances in metabolic therapies over the past decade, their efficacy in melanoma has been modest, largely due to the interaction between cancer-associated fibroblasts (CAFs) and cancer cells to promote cancer growth. Altering the tumor microenvironment (TME) is challenging and elusive. CAFs is critical for glutamine deprivation survival in melanoma. In this research, we assembled a CAFs-targeted, controlled-release nanodroplets for the combined delivery of the amino acid transporter ASCT2 (SLC1A5) inhibitor V9302 and GLULsiRNA (siGLUL). The application of ultrasound-targeted microbubble disruption (UTMD) allows for rapid release of V9302 and siGLUL, jointly breaking the glutamine metabolism interaction between CAFs and cancer cells on one hand, on the other hand, blocking activated CAFs and reducing the expression of extracellular matrix (ECM) to facilitate drug penetration. In addition, ultrasound stimulation made siGLUL more accessible to tumor cells and CAFs, downregulating GLUL expression in both cell types. FH-V9302-siGLUL-NDs also serve as contrast-enhanced ultrasound imaging agents for tumor imaging. Our study developed and reported FH-NDs as nanocarriers for V9302 and siGLUL, demonstrating that FH-V9302-siGLUL-NDs have potential bright future applications for integrated diagnostic therapy. Graphical Abstract

In our previous study, a new fermented food (PWF) created by utilizing pineapple by-products and whey proteins as a matrix via co-fermentation with lactic acid bacteria and yeast was developed, and, in the current study, we examined the impact of a pineapple–whey protein fermentation product on a cefixime-induced dysbiosis model in mice using 16S sequencing and untargeted metabolomics techniques. The results indicated that the pineapple–whey protein fermentation product played a positive role in restoring the intestinal flora. In this study, cefixime reduced the overall abundance of intestinal flora and decreased the relative abundance of probiotics in the gut, while also inhibiting amino acid metabolism. The addition of PWF normalized the intestinal flora to a steady state, significantly increasing the populations of Weissella, Lactococcus, Faecalibaculum, and Bacteroides acidophilus, while decreasing the numbers of Akkermansia and Escherichia-Shigella. Additionally, PWF modulated microbial metabolites, such as L-glutamate and L-threonine, and upregulated amino-acid-related metabolic pathways, including those involving glycine, serine, and threonine. In conclusion, PWF can alleviate intestinal flora dysbiosis and metabolic disturbances induced by antibiotic interventions. It is suggested that PWF could be a potential dietary strategy for patients with antibiotic-associated diarrhea.

In this study, we developed an ultrasound-assisted alkaline method for extracting black soldier fly larvae protein (BSFLP). The effects of ultrasound-assisted extraction on the nutritional value, structural characteristics, and techno-functional properties of BSFLP were compared with those using the conventional hot alkali method. The results showed that ultrasound-assisted extraction significantly increased the extraction ratio of BSFLP from 55.40% to 80.37%, but reduced the purity from 84.19% to 80.75%. The BSFLP extracted by ultrasound-assisted extraction met the amino acid requirements for humans proposed by the Food and Agriculture Organization in 2013, and ultrasound-assisted extraction did not alter the limiting amino acids of the BSFLP. The ultrasound-assisted extraction increased the in vitro protein digestibility from 82.97% to 99.79%. Moreover, ultrasound-assisted extraction obtained BSFLP with a more ordered secondary structure and more loosely porous surface morphology, without breaking the peptide bonds. By contrast, the conventional hot alkaline method hydrolyzed BSFLP into smaller fragments. The effect of ultrasound-assisted extraction on the structure of BSFLP improved the solubility and emulsion capacity of BSFLP, but reduced its foaming properties. In conclusion, the results of this study suggest that ultrasound-assisted alkaline extraction could be a suitable method for extracting BSFLP and improving its nutritional value, and structural and functional properties. The findings obtained in this study could promote the wider application of BSFLP in food industry.

Background The inter-relationships among neutrophilic airway inflammation, air trapping and future exacerbation in chronic obstructive pulmonary disease (COPD) remain unclear.Objective To evaluate the associations between sputum neutrophil proportions and future exacerbation in COPD and to determine whether these associations are modified by significant air trapping.Methods Participants with completed data were included and followed up to the first year in the Early Chronic Obstructive Pulmonary Disease study (n=582). Sputum neutrophil proportions and high-resolution CT-related markers were measured at baseline. Sputum neutrophil proportions were dichotomised based on their median (86.2%) to low and high levels. In addition, subjects were divided into the air trapping or non-air trapping group. Outcomes of interest included COPD exacerbation (separately any, severe and frequent exacerbation, occurring in the first year of follow-up). Multivariable logistic regressions were performed to examine the risk of severe exacerbation and frequent exacerbation with either neutrophilic airway inflammation groups or air trapping groups.Results There was no significant difference between high and low levels of sputum neutrophil proportions in the exacerbation in the preceding year. After the first year of follow-up, subjects with high sputum neutrophil proportions had increased risks of severe exacerbation (OR=1.68, 95% CI: 1.09 to 2.62, p=0.020). Subjects with high sputum neutrophil proportions and significant air trapping had increased odds of having frequent exacerbation (OR=3.29, 95% CI: 1.30 to 9.37, p=0.017) and having severe exacerbation (OR=2.72, 95% CI: 1.42 to 5.43, p=0.003) when compared with those who had low sputum neutrophil proportions and non-air trapping.Conclusions We found that subjects with high sputum neutrophil proportions and significant air trapping are prone to future exacerbation of COPD. It may be a helpful predictor of future exacerbation.

Background Evidence regarding clinical features and outcomes of individuals with non-obstructive chronic bronchitis (NOCB) remains scarce, especially in never-smokers. We aimed to investigate the clinical features and 1-year outcomes of individuals with NOCB in the Chinese population.Methods We obtained data on participants in the Early Chronic Obstructive Pulmonary Disease Study who had normal spirometry (post-bronchodilator forced expiratory volume in 1 s/forced vital capacity ≥0.70). NOCB was defined as chronic cough and sputum production for at least 3 months for two consecutive years or more at baseline in participants with normal spirometry. We assessed the differences in demographics, risk factors, lung function, impulse oscillometry, CT imaging and frequency of acute respiratory events between participants with and without NOCB.Results NOCB was present in 13.1% (149/1140) of participants with normal spirometry at baseline. Compared with participants without NOCB, those with NOCB had a higher proportion of men and participants with smoke exposure, occupational exposure, family history of respiratory diseases and worse respiratory symptoms (all p

Background The relationship between airway inflammation in chronic obstructive pulmonary disease (COPD) and clinical characteristics remains unclear. This study aimed to investigate the airway inflammatory phenotypes in COPD and their association with clinical characteristics.Methods 895 patients with COPD were recruited from Guangdong Province, China in this study. Each patient underwent questionnaire interviews, spirometry testing, CT scans and induced sputum examination. Classification of airway inflammation phenotypes was based on sputum inflammatory cell counts. Covariance analysis was applied to assess associations with airway inflammation phenotypes.Results In this study, we found that neutrophilic phenotype (NP, 58.0%) was the most common airway inflammation phenotype in patients with COPD, followed by mixed granulocytic phenotype (MGP, 32.6%), eosinophilic phenotype (EP, 5.4%) and paucigranulocytic phenotype (PP, 4.0%). Compared with NP patients, those with MGP exhibited more frequent chronic respiratory symptoms, and a higher proportion of individuals classified under Global Initiative for Chronic Obstructive Lung Disease stages 3 and 4. After adjusting for confounding factors, MGP patients had lower lung function, and more severe emphysema and air trapping. On the contrary, patients with PP had the best pulmonary function and less emphysema and air trapping.Conclusions NP was the most common airway inflammation phenotype in patients with COPD. Patients with MGP had more respiratory symptoms, greater loss of lung function, and more severe emphysema and gas trapping compared with those with NP. Meanwhile, PP may be a phenotype of mild damage to lung structure in patients with COPD.

Abstract The ectoparasitoid wasp Theocolax elegans is a cosmopolitan and generalist pteromalid parasitoid of several major storage insect pests, and can effectively suppress a host population in warehouses. However, little molecular information about this wasp is currently available. In this study, we assembled the genome of T. elegans using PacBio long-read sequencing, Illumina sequencing, and Hi-C methods. The genome assembly is 662.73 Mb in length with contig and scaffold N50 values of 1.15 Mb and 88.8 Mb, respectively. The genome contains 56.4% repeat sequences and 23,212 protein-coding genes were annotated. Phylogenomic analyses revealed that T. elegans diverged from the lineage leading to subfamily Pteromalinae (Nasonia vitripennis and Pteromalus puparum) approximately 110.5 million years ago. We identified 130 significantly expanded gene families, 34 contracted families, 248 fast-evolving genes, and 365 positively selected genes in T. elegans. Additionally, 260 olfactory receptors and 285 venom proteins were identified. This genome assembly provides valuable genetic bases for future investigations on evolution, molecular biology and application of T. elegans.

Abstract Nanosized drug delivery systems have rapidly emerged as a promising approach to tumor therapy, which still have many challenges in clinical application. In this study, doxorubicin-loaded O-carboxymethyl chitosan/perfluorohexane nanodroplets (O-CS-DOX NDs) were synthesized and functionally tested as an effective drug delivery system in vitro and in vivo. O-CS-DOX NDs with small size (159.6 nm) and good doxorubicin encapsuling ability showed pH- and ultrasound-dependent drug release profile and satisfying ultrasound imaging performance. With high biocompatibility and biosafety, these nanodroplets could accumulate in the tumor sites and exhibit high efficiency in inhibiting tumor growth with ultrasound irradiation. These stable, safe and smart O-CS-DOX NDs showed promising potential as a smart dual-responsive bomb for tumor ultrasonic imaging and treatment.

Abstract Background The role of airway impairment assessed by impulse oscillometry (IOS) in patients with chronic obstructive pulmonary disease (COPD) remains unclear. Therefore, this study aimed to analyze the proportion and clinical characteristics of airway impairment assessed by IOS across COPD severities, and explore whether airway impairment is a subtype of COPD. Methods This study was based on cross-sectional data from the ECOPD cohort in Guangdong, China. Subjects were consecutively recruited from July 2019 to August 2021. They filled out questionnaires and underwent lung function tests, IOS and computed tomography (CT). COPD was defined as post-bronchodilator forced expiratory volume in one second/forced vital capacity upper limit of normal or

We have previously shown that healthy subjects can transfer coordination skills to the unpracticed hand by performing a unimanual task with the other hand and visualizing a bimanual action using a game-like interactive system. However, whether this system could be used to transfer coordination skills to the paretic hand after stroke and its underlying neural mechanism remain unknown. Here, using a game-like interactive system for visualization during physical practice in an immersive virtual reality environment, we examined coordination skill improvement in the unpracticed/paretic hand after training in 10 healthy subjects and 13 chronic and sub-acute stroke patients. The bimanual movement task was defined as simultaneously drawing non-symmetric three-sided squares (e.g., U and C), while the training strategy was performing a unimanual task with the right/nonparetic hand and visualizing a bimanual action. We found large decreases in the intra-hand temporal and spatial measures for movement in the unpracticed/paretic hand after training. Furthermore, a substantial reduction in the inter-hand temporal and spatial interference was observed after training. Additionally, we examined the related cortical network evolution using EEG in both the healthy subjects and stroke patients. Our studies show that the cortical network became more efficient after training in the healthy subjects and stroke patients. These results demonstrate that our proposed method could contribute to the transference of coordination skill to the paretic/unpracticed hand by promoting the efficiency of cortical networks.

In order to rapidly determine deoxynivalenol (DON) and Zearalenone (ZEN) in maize, a rapid quantitative immunofluorescence assay based on superconductor coating was used to detect multiple maize samples. Combined with the recovery rate, stability, detection limit, precision and other indexes, the applicability of the method was evaluated and compared with the results of liquid chromatography. The results showed that the superconductor coated immunofluorescence diaper method had the good linearity in the range of 100 ng/mL~2 500 ng/mL for DON and 5~200 µg/kg for ZEN. The recoveries of DON were 103.72%~108.17% in the range of 500~2 000 µg/kg, and 97.81%~111.27% in the range of ZEN 50~150 µg/kg. Compared with the results of liquid chromatography, the superconductor coated immunofluorescence diaper method is an effective, practical, rapid and quantitative analysis method within the allowable deviation range, which can meet the requirements of simultaneous detection of DON and ZEN in maize.

Abstract Immunotherapy had demonstrated inspiring effects in tumor treatment, but only a minority of people could benefit owing to the hypoxic and immune-suppressed tumor microenvironment (TME). Therefore, there was an urgent need for a strategy that could relieve hypoxia and increase infiltration of tumor lymphocytes simultaneously. In this study, a novel acidity-responsive nanoscale ultrasound contrast agent (L-Arg@PTX nanodroplets) was constructed to co-deliver paclitaxel (PTX) and L-arginine (L-Arg) using the homogenization/emulsification method. The L-Arg@PTX nanodroplets with uniform size of about 300 nm and high drug loading efficiency displayed good ultrasound diagnostic imaging capability, improved tumor aggregation and achieved ultrasound-triggered drug release, which could prevent the premature leakage of drugs and thus improve biosafety. More critically, L-Arg@PTX nanodroplets in combination with ultrasound targeted microbubble destruction (UTMD) could increase cellular reactive oxygen species (ROS), which exerted an oxidizing effect that converted L-Arg into nitric oxide (NO), thus alleviating hypoxia, sensitizing chemotherapy and increasing the CD8 + cytotoxic T lymphocytes (CTLs) infiltration. Combined with the chemotherapeutic drug PTX-induced immunogenic cell death (ICD), this promising strategy could enhance immunotherapy synergistically and realize powerful tumor treatment effect. Taken together, L-Arg@PTX nanodroplets was a very hopeful vehicle that integrated drug delivery, diagnostic imaging, and chemoimmunotherapy. Graphical Abstract

In some countries, yeasts are still not allowed in the production of commercially fermented sausages. Therefore, further research is needed on producing fermented meat products using different strains of yeasts. In this study, two strains of Debaryomyces hansenii (D. hansenii Y61 and Y67) were inoculated in fermented sausages to study their effects as starter cultures. The inoculation of D. hansenii strains affected ripening by decreasing the pH and aw. The sausages inoculated with Y61 and Y67 exhibited decreases in lipid oxidation of 40.70% and 36.04%, respectively, and Enterobacteriaceae counts of 50% and 100%, respectively. The inoculating yeasts Y61 and Y67 increased the lightness (L*) and redness (a*) of fermented sausages. The D. hansenii-inoculated sausages had higher levels of free amino acids and fatty acids, which improved the digestibility, sensory value, and safety of these sausages. Moreover, the total amount of ester compounds increased by 87.14% and 83.31% in the Y61- and Y67-inoculated groups, respectively, which contributed to the aroma. Better sensory attributes were also found in the sausages inoculated with Y61 and Y67 D. hansenii. Native D. hansenii Y61 and Y67 are, therefore, good starter cultures for fermented sausage production. Together, the results provide data supporting future research and the use of yeast-fermented sausages.

Alternative splicing (AS) is a major source of protein diversity in eukaryotes, but less is known about its evolution compared to gene duplication (GD). How AS and GD interact is also largely understudied. By constructing the evolutionary trajectory of the serpin gene PpSerpin-1 (Pteromalus puparum serpin 1) in parasitoids and other insects, we found that both AS and GD jointly contribute to serpin protein diversity. These two processes are negatively correlated and show divergent features in both protein and regulatory sequences. Parasitoid wasps exhibit higher numbers of serpin protein/domains than nonparasitoids, resulting from more GD but less AS in parasitoids. The potential roles of AS and GD in the evolution of parasitoid host-effector genes are discussed. Furthermore, we find that PpSerpin-1 shows an exon expansion of AS compared to other parasitoids, and that several isoforms are involved in the wasp immune response, have been recruited to both wasp venom and larval saliva, and suppress host immunity. Overall, our study provides an example of how a parasitoid serpin gene adapts to parasitism through AS, and sheds light on the differential features of AS and GD in the evolution of insect serpins and their associations with the parasitic life strategy.

IntroductionKefir grains with efficient proteolytic system is an excellent starter culture for the production of bioactive peptides and milk products. This study explores the casein peptides derived from fermented bovine milk by kefir grains using the peptidomics approaches. The angiotensin converting enzyme (ACE) inhibitory activity of these peptides were also investigated.MethodsAfter fermentation, peptidomics based on the LC-MS/MS was used to investigate the dynamic profile and the structure specificity of generated peptides. The ACE inhibitory activity of peptides was determined by measuring the amount of hippuric acid (HA) by a spectrophotometer at 228 nm.ResultsThe results indicated that the cell envelope proteinases (CEPs) were the PI-/PIII-type. A total of 122 peptides were identified. The β-casein was preferentially hydrolyzed by kefir grains, and the main hydrolysis regions were f57-93, f132-160 and f192-209. The αs1-, and κ-casein were also hydrolyzed by a weaker degree. In the process of fermentation, the accumulated peptides increased with the fermentation time. The fermentation products exhibited ACE inhibitory activity, and this bioactivity remained 63% after simulated gastrointestinal (GI) digestion in vitro. Additionally, 14 Pro-containing peptides with ACE inhibitory activity were also identified.ConclusionThese results provide new insights and evidence to investigate the bioactive milk peptides generated by kefir grains fermentation, as well as a reference for the development of functional foods.

Chloride intracellular channel (CLIC) is a member of the chloride channel protein family for which growing evidence supports a pivotal role in fundamental cellular events. However, the physiological function of CLIC in insects is still rarely uncovered. The ovary-derived High Five (Hi-5) cell line isolated from the cabbage looper (Trichoplusia ni) is widely used in laboratories. Here, we studied both characteristics and functions of CLIC in Hi-5 cells (TnCLIC). We identified the TnCLIC gene in Hi-5 cells and annotated highly conserved CLIC proteins in most insect species. After RNA interference of TnCLIC, the phenomenon of significantly increased cell death suggests that the TnCLIC protein is essential for the survival of Hi-5 cells. The same lethal effect was also observed in Spodoptera frugiperda 9 and Drosophila melanogaster Schneider 2 cells after CLIC knockdown. Furthermore, we found that this kind of cell death was accompanied by increases in intracellular calcium ions after TnCLIC knockdown with the transcriptomic analyses and the detection of calcium levels. Our results provide insights into insect CLIC as a key factor for cell survival and lay the foundation for the cell death mechanism.

Abstract Background: Preserved ratio impaired spirometry (PRISm) refers to decreased forced expiratory volume in 1 s (FEV1) in the setting of preserved ratio. Little is known about the role of PRISm and its complex relation with small airway dysfunction (SAD) and lung volume. Therefore, we aimed to investigate the associations between PRISm and SAD and lung volume. Methods: We conducted a cross-sectional community-dwelling study in China. Demographic data, standard respiratory epidemiology questionnaire, spirometry, impulse oscillometry (IOS) and computed tomography (CT) data were collected. PRISm was defined as post-bronchodilator FEV1/FVC ≥ 0.70 and FEV1 0.07 kPa/L/s and LAA− 856>20%, respectively. Analysis of covariance and logistic regression were used to determine associations between PRISm and SAD and lung volume. We then repeated the analysis with a lower limit of normal definition of spirometry criteria and FVC definition of PRISm. Moreover, we also performed subgroup analyses in ever smoker, never smoker, subjects without airway reversibility or self-reported diagnosed asthma, and subjects with CT-measured total lung capacity ≥70% of predicted. Results: The final analysis included 1439 subjects. PRISm had higher odds and more severity in spirometry-defined SAD (pre-bronchodilator: odds ratio [OR]: 5.99, 95% confidence interval [95%CI]: 3.87–9.27, P

Parasitoid wasps are rapidly developing as a model for evolutionary biology. Here, the authors analyze the genomes of two Anastatus wasps, revealing genomic innovations related to maintenance of genomic stability, and rapid turnover of venom genes.

Abstract Background Aging has been evidenced to bring about some structural and functional lung changes, especially in COPD. However, whether aging affects SAD, a possible precursor of COPD, has not been well characterized. Objective We aimed to comprehensively assess the relationship between aging and SAD from computed tomography, impulse oscillometry, and spirometry perspectives in Chinese. Methods We included 1859 participants from ECOPD, and used a linear-by-linear association test for evaluating the prevalence of SAD across various age subgroups, and multivariate regression models for determining the impact of age on the risk and severity of SAD. We then repeated the analyses in these subjects stratified by airflow limitation. Results The prevalence of SAD increases over aging regardless of definitional methods. After adjustment for other confounding factors, per 10-yrs increase in age was significantly associated with the risk of CT-defined SAD (OR 2.57, 95% CI 2.13 to 3.10) and the increase in the severity of air trapping (β 2.09, 95% CI − 0.06 to 4.25 for LAA-856), airway reactance (β − 0.02, 95% CI − 0.04 to − 0.01 for X5; β 0.30, 95% CI 0.13 to 0.47 for AX; β 1.75, 95% CI 0.85 to 2.66 for Fres), as well as the decrease in expiratory flow rates (β − 3.95, 95% CI − 6.19 to − 1.71 for MMEF%predicted; β − 5.42, 95% CI − 7.88 to − 2.95 for FEF50%predicted) for SAD. All these associations were generally maintained in SAD defined by IOS or spirometry. After stratification of airflow limitation, we further found that the effect of age on LAA-856 was the most significant among almost all subgroups. Conclusions Aging is significantly associated with the prevalence, increased risk, as well as worse severity of SAD. CT may be a more optimal measure to assess aging-related SAD. The molecular mechanisms for the role of aging in SAD need to be explored in the future. Trial registration Chinese Clinical Trial Registry ChiCTR1900024643. Registered on 19 July 2019

Abstract Precision medicine in hepatocellular carcinoma (HCC) relies on validated biomarkers that help subgroup patients for targeted treatment. Here, we identified a novel candidate oncogene, ribosomal protein L22-like1 (RPL22L1), which was markedly elevated in HCC, contributed to HCC malignancy and adverse patient survival. Functional studies indicated RPL22L1 overexpression accelerated cell proliferation, migration, invasion and sorafenib resistance. Mechanism studies revealed that RPL22L1 activated ERK to induce atypical epithelial-to-mesenchymal transition (EMT) progress. Importantly, the ERK inhibitor (ERKi) could potentiate sorafenib efficiency in RPL22L1-high HCC cells. In summary, these data uncover RPL22L1 is a potential marker to guide precision therapy for utilizing ERKi to enhance the sorafenib efficacy in RPL22L1-high HCC patients.

The linker histone H1 binds to the nucleosome core particle at the site where DNA enters and exits, and facilitates folding of the nucleosomes into a higher-order chromatin structure in eukaryotes. Additionally, some variant H1s promote specialized chromatin functions in cellular processes. Germline-specific H1 variants have been reported in some model species with diverse roles in chromatin structure changes during gametogenesis. In insects, the current understanding of germline-specific H1 variants comes mainly from the studies in Drosophila melanogaster, and the information on this set of genes in other non-model insects remains largely unknown. Here, we identify two H1 variants (PpH1V1 and PpH1V2) that are specifically predominantly expressed in the testis of the parasitoid wasp Pteromalus puparum. Evolutionary analyses suggest that these H1 variant genes evolve rapidly, and are generally maintained as a single copy in Hymenoptera. Disruption of PpH1V1 function in the late larval stage male by RNA interference experiments has no phenotype on spermatogenesis in the pupal testis, but results in abnormal chromatin structure and low sperm fertility in the adult seminal vesicle. In addition, PpH1V2 knockdown has no detectable effect on spermatogenesis or male fertility. Collectively, our discovery indicates distinct functions of male germline-enriched H1 variants between parasitoid wasp Pteromalus and Drosophila, providing new insights into the role of insect H1 variants in gametogenesis. This study also highlights the functional complexity of germline-specific H1s in animals.

Both parasitoids and entomopathogenic fungi are becoming increasingly crucial for managing pest populations. Therefore, it is essential to carefully consider the potential impact of entomopathogenic fungi on parasitoids due to their widespread pathogenicity and the possible overlap between these biological control tools during field applications. However, despite their importance, little research has been conducted on the pathogenicity of entomopathogenic fungi on parasitoids. In our study, we aimed to address this knowledge gap by investigating the interaction between the well-known entomopathogenic fungus Beauveria bassiana, and the pupal endoparasitoid Pteromalus puparum. Our results demonstrated that the presence of B. bassiana significantly affected the survival rates of P. puparum under laboratory conditions. The pathogenicity of B. bassiana on P. puparum was dose- and time-dependent, as determined via through surface spraying or oral ingestion. RNA-Seq analysis revealed that the immune system plays a primary and crucial role in defending against B. bassiana. Notably, several upregulated differentially expressed genes (DEGs) involved in the Toll and IMD pathways, which are key components of the insect immune system, and antimicrobial peptides were rapidly induced during both the early and late stages of infection. In contrast, a majority of genes involved in the activation of prophenoloxidase and antioxidant mechanisms were downregulated. Additionally, we identified downregulated DEGs related to cuticle formation, olfactory mechanisms, and detoxification processes. In summary, our study provides valuable insights into the interactions between P. puparum and B. bassiana, shedding light on the changes in gene expression during fungal infection. These findings have significant implications for the development of more effective and sustainable strategies for pest management in agriculture.

microRNAs (miRNAs) and small interfering RNAs (siRNAs) are small non-coding RNAs (ncRNAs) that trigger RNA interference (RNAi) in eukaryotic organisms. The biogenesis pathways for these ncRNAs are well established in Drosophila melanogaster, Aedes aegypti, Bombyx mori and other insects, but lacking in hymenopteran species, particularly in parasitoid wasps. Pteromalus puparum is a parasitoid of pupal butterflies. This study identified and analyzed two pathways by interrogating the P. puparum genome. All core genes of the two pathways are present in the genome as a single copy, except for two genes in the siRNA pathway, R2D2 (two copies) and Argonaute-2 (three). Conserved domain analyses showed the protein structures in P. puparum were similar to cognate proteins in other insect species. Phylogenetic analyses of hymenopteran Dicer and Argonaute genes suggested that the siRNA pathway-related genes evolved faster than those in the miRNA pathway. The study found a decelerated evolution rate of P. puparum Dicer-2 with respect to Dicer-1, which was contrary to other hymenopterans. Expression analyses revealed high mRNA levels for all miRNA pathway genes in P. puparum adults and the siRNA related genes were expressed in different patterns. The findings add valuable new knowledge of the miRNA and siRNA pathways and their regulatory actions in parasitoid wasps.

Alternative polyadenylation (APA) is a molecular process that generates diversity at the 3’ end of RNA polymerase II transcripts from over 60% of human genes. APA and microRNA regulation are both mechanisms of post-transcriptional regulation of gene expression. As a key molecular mechanism, Alternative polyadenylation often results in mRNA isoforms with the same coding sequence but different lengths of 3’ UTRs, while microRNAs regulate gene expression by binding to specific mRNA 3’ UTRs. Nudix Hydrolase 21 (NUDT21) is a crucial mediator involved in alternative polyadenylation (APA). Different studies have reported a dual role of NUDT21 in cancer (both oncogenic and tumor suppressor). The present review focuses on the functions of APA, miRNA and their interaction and roles in development of different types of tumors.NUDT21 mediated 3’ UTR-APA changes can be used to generate specific signatures that can be used as potential biomarkers in development and disease. Due to the emerging role of NUDT21 as a regulator of the aforementioned RNA processing events, modulation of NUDT21 levels may be a novel viable therapeutic approach.

Abstract Objective The current study was undertaken to investigate the relationship between antimüllerian hormone (AMH) and polycystic ovarian syndrome (PCOS) phenotypes and to determine whether AMH is associated with pregnancy outcomes in infertile women undergoing their first in vitro fertilization (IVF) treatment. Methods We performed a retrospective cohort study of 2973 infertile women, including 418 women with PCOS undergoing their first IVF treatment at a private fertility center from January 2014 to March 2018. Women were stratified into three groups using cutoffs defined by the 25th and 75th percentiles of the serum AMH level: 746 women had AMH ≤ 2.25 ng/mL; 1486 women had AMH between 2.25 to 5.71 ng/mL; and 741 women had AMH > 5.71 ng/mL. Endocrine characteristics, PCOS phenotypes, stimulation outcomes, pregnancy outcomes were compared among these groups. When there were any statistical differences (P

Abstract Background The lack of simple and affordable spirometry has led to the missed and delayed diagnoses of chronic respiratory diseases in communities. The PUS201P is a portable spirometry developed to solve this problem. Objective We aimed to verify the consistency of the PUS201P spirometer with conventional Jaeger spirometer. Methods In this cross-sectional study, we randomly recruited 202 subjects aged > 40 years. Testing with the portable spirometry and conventional spirometry were performed on all participants. We compared forced expiratory volume in one second (FEV1), forced vital capacity (FVC), FEV1/FVC measured by the PUS201P device with the conventional spirometer. Pearson correlation coefficient and Interclass Correlation Coefficient (ICC) were assessed to confirm the consistency of the measures from two instruments. Bland–Altman graph was created to assess the agreement of the measures from two devices. Results 202 participants were included in this study. The ICC on FEV1, FVC, FEV1/FVC measured by the portable spirometer and the conventional spirometer were 0.95 (95% confidence interval [CI]: 0.94–0.96), 0.92 (95% CI: 0.90–0.94], 0.93 (95% CI: 0.91–0.95), respectively. The Bland–Altman plots showed that the mean difference between the measures from two spirometers are always located in the 95% limits of agreement. Conclusions Our results support that the measures from the portable spirometer and the conventional spirometer have a good agreement and reproducibility. And the portable spirometer is a reliable tool to screen and diagnose chronic airway diseases in the primary care settings.

Compared to the construction phase, the assessment of tunnel safety risks during the operational stage has not been thoroughly conducted, and the related research work is relatively lagging. To deepen the research and application of theoretical methods for assessing operational tunnel safety risks, and to improve the level of hazard investigation and prevention in long and large highway tunnels, this paper establishes a tunnel section assessment index system from four perspectives: tunnel condition, traffic characteristics, operational environment, and operational management. A combined qualitative and quantitative approach is employed, and a practical classification standard for the indicators is proposed. Based on the traditional Analytic Hierarchy Process (AHP) and fuzzy analysis theory, a new form of questionnaire survey, known as the expert system analysis method, is introduced to collect expert opinions. A novel approach for determining fuzzy numbers based on expert opinions is proposed. Consequently, a combined model for assessing operational tunnel safety risks in long and large highways is established by integrating the Fuzzy Analytic Hierarchy Process (FAHP) and the Set Pair Analysis (SPA). This model effectively combines subjective weighting with objective evaluation, thereby enhancing the accuracy of operational tunnel safety risk assessment for long and large highways. The safety risks of three long and large tunnels within the G1523 Yongguan Expressway were assessed using the evaluation method proposed in this paper. A comparative analysis was conducted between the results obtained using the proposed Fuzzy Analytic Hierarchy Process (FAHP) and Set Pair Analysis (SPA) method and the traditional Analytic Hierarchy Process (AHP) evaluation. The results indicate that the operational tunnel safety risk assessment method based on FAHP and SPA exhibits greater rationality and accuracy compared to the traditional AHP approach.

Objective The aim of this work was to assess the effect of ergothioneine (ESH)-enriched mushroom extract on oxidative stability, volatile compounds, and sensory quality of emulsified sausage. Methods The ESH content was determined by high performance liquid chromatography. The antioxidant activity of Flammulina velutipes (F. velutipes) extract was determined through radical-scavenging activity of 1,1 diphenyl-2-picryl-hydrazyl, 2,2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) and hydroxyl radicals. Four different groups of emulsified sausage were manufactured: control, no antioxidants; BHA, 0.01% butylated hydroxyanisole; EEME, 0.8% ESH-enriched mushroom (F. velutipes) extract; AE, 0.012% authentic ESH, after storage for 14 days (at 4°C), the quality of sausage including oxidative stability (2-thiobarbituric acid reactive substances and protein carbonyls content), volatile compounds and sensory quality were studied. Results It was demonstrated that adding ESH-enriched F. velutipes extract to sausage could effectively prevent lipid and protein oxidation, and its efficacy was equivalent with 0.01% BHA. During meat processing, the ESH mainly contributed to the antioxidative activity of F. velutipes extract. The flavor and sensory attributes of emulsified sausage were improved through adding ESH-enriched F. velutipes extract. Conclusion Accordingly, the extract of F. velutipes contained high-level of ESH and could be a good antioxidant candidate for processed meat production.

With the rise of global urbanization, the rural built environment has undergone tremendous changes. As such, the rural built environment impacts on residents’ daily travel behavior is getting more researchers’ attention. To date, most of the research focuses on urban areas in developed countries. To understand the state-of-the-art of interplay between the rural built environment and travel behaviors and to identify future research directions, this study adopts a science mapping approach to identify the relevant topics, authors, journals, and countries of the research done. This study proceeds through bibliometric retrieval of articles from 2005, followed by scientometric analysis and qualitative discussion. 37 documents are found to compare urban and rural domains, with 28 on the rural built environment. Research gaps and the research trends are discussed, of which the main themes are multi-dimensional correlation comparison of rural transportation service systems and emerging transportation modes, the influence of rural social and cultural factors on travel behavior, and low-carbon sustainable transportation. This review provides empirical foundation for current state-of-the-art and identifies the future research directions, specifically for rural built environment impact on travel behavior.

Abstract Background Hymenoptera comprise extremely diverse insect species with extensive variation in their life histories. The Dryinidae, a family of solitary wasps of Hymenoptera, have evolved innovations that allow them to hunt using venom and a pair of chelae developed from the fore legs that can grasp prey. Dryinidae larvae are also parasitoids of Auchenorrhyncha, a group including common pests such as planthoppers and leafhoppers. Both of these traits make them effective and valuable for pest control, but little is yet known about the genetic basis of its dual adaptation to parasitism and predation. Results We sequenced and assembled a high-quality genome of the dryinid wasp Gonatopus flavifemur, which at 636.5 Mb is larger than most hymenopterans. The expansion of transposable elements, especially DNA transposons, is a major contributor to the genome size enlargement. Our genome-wide screens reveal a number of positively selected genes and rapidly evolving proteins involved in energy production and motor activity, which may contribute to the predatory adaptation of dryinid wasp. We further show that three female-biased, reproductive-associated yellow genes, in response to the prey feeding behavior, are significantly elevated in adult females, which may facilitate the egg production. Venom is a powerful weapon for dryinid wasp during parasitism and predation. We therefore analyze the transcriptomes of venom glands and describe specific expansions in venom Idgf-like genes and neprilysin-like genes. Furthermore, we find the LWS2-opsin gene is exclusively expressed in male G. flavifemur, which may contribute to partner searching and mating. Conclusions Our results provide new insights into the genome evolution, predatory adaptation, venom evolution, and sex-biased genes in G. flavifemur, and present genomic resources for future in-depth comparative analyses of hymenopterans that may benefit pest control.

BackgroundLymphangioleiomyomatosis (LAM) is a rare low-grade metastatic tumor with an unknown origin that spreads through lymphatic vessels. It is characterized by the proliferation of smooth muscle-like or epithelioid tumor cells in the lung and axial lymphatic system. Extrapulmonary LAM is a localized disease with a low incidence rate, and the location of the related lesions is atypical. It is difficult to diagnose. The LAM of pelvic lymph nodes is hidden. It is usually found through gynecological oncology surgery.Case presentationWe report a 57-year-old postmenopausal woman with a pelvic mass and vaginal bleeding as the main symptoms. The patient had no history of pulmonary LAM, tuberous sclerosis complex (TSC), or renal angiomyolipoma and had not used exogenous hormones. We performed a total hysterectomy, bilateral adnexectomy, greater omentum resection, and pelvic lymphadenectomy under laparoscopy. The postoperative pathology confirmed high-grade serous carcinoma of the left fallopian tube, and four lymph nodes were found in the pelvic lymph nodes, suggesting lymphangiomyomatosis. Immunohistochemical results also showed that these cells could express markers of smooth muscle cells and melanoma cells. The patient was treated with chemotherapy after the operation. Chest CT did not suggest lung LAM during the postoperative follow-up, and there was no tumor recurrence.ConclusionThe diagnosis of this disease is challenging. At the same time, due to insufficient clinical samples, it is still unknown whether there is a potential relationship between pelvic and peritoneal lymph node LAM found in the surgical staging of gynecological tumors and lung LAM and/or TSC. There is no evidence that pelvic and peritoneal lymph node LAM will increase the risk of pulmonary LAM. Therefore, additional clinical data are required to analyze and summarize the relationship between pelvic and peritoneal lymph node LAM, pulmonary LAM, and the source of LAM. We present a case of pelvic lymph node LAM and propose a hypothesis that the pathogenesis of endometriosis can be used for reference in the study of this disease.

The methyltransferase complex of METTL3-METTL14-WTAP is responsible for m6A modification on RNA. Here the authors report that METTL14 arginine 255 (R255) is methylated by PRMT1 and this modification increases interaction of METTL3/METTL14 interaction with WTAP and substrate RNA, promoting m6A methylation activity of the complex.

Background and objective: Spirometry is commonly used to assess small airway dysfunction (SAD). Impulse oscillometry (IOS) can complement spirometry. However, discordant spirometry and IOS in the diagnosis of SAD were not uncommon. We examined the association between spirometry and IOS within a large cohort of subjects to identify variables that may explain discordant spirometry and IOS findings.Methods: 1,836 subjects from the ECOPD cohort underwent questionnaires, symptom scores, spirometry, and IOS, and 1,318 subjects were examined by CT. We assessed SAD with R5-R20 > the upper limit of normal (ULN) by IOS and two of the three spirometry indexes (maximal mid-expiratory flow (MMEF), forced expiratory flow (FEF)50%, and FEF75%) < 65% predicted. Multivariate regression analysis was used to analyze factors associated with SAD diagnosed by only spirometry but not IOS (spirometry-only SAD) and only IOS but not spirometry (IOS-only SAD), and line regression was used to assess CT imaging differences.Results: There was a slight agreement between spirometry and IOS in the diagnosis of SAD (kappa 0.322, p < 0.001). Smoking status, phlegm, drug treatment, and family history of respiratory disease were factors leading to spirometry-only SAD. Spirometry-only SAD had more severe emphysema and gas-trapping than IOS-only SAD in abnormal lung function. However, in normal lung function subjects, there was no statistical difference in emphysema and gas-trapping between discordant groups. The number of IOS-only SAD was nearly twice than that of spirometry.Conclusion: IOS may be more sensitive than spirometry in the diagnosis of SAD in normal lung function subjects. But in patients with abnormal lung function, spirometry may be more sensitive than IOS to detect SAD patients with clinical symptoms and CT lesions.

The aim of this work was to identify the transcriptomic characteristics of the endometrium in normoweight and overweight/obese polycystic ovary syndrome (PCOS) potentially underlying the pathogenesis. This study included 38 patients undergoing in vitro fertilization: 22 women with PCOS and 16 matched controls. Each of the groups was subdivided into normoweight (body mass index (BMI) < 25 kg/m2) and overweight/obese (BMI ≥25 kg/m2) subgroups. Endometrium samples were collected in the secretory phase from controls or in a modeled secretory phase using daily administration of progesterone from women with PCOS before in vitro fertilization treatment. Transcriptome profiles were assessed by high-throughput RNA sequencing to investigate distinct endometrial gene expression patterns in PCOS. Bioinformatics analyses revealed that the endometrium from PCOS expresses significantly different transcripts encoding endometrial receptivity, inflammatory response, angiogenesis, and energy metabolism. Additionally, our study demonstrated that the differentially expressed genes between normoweight and overweight/obese PCOS are involved in fatty acid metabolism, endometrial decidualization, and immune response. For the first time, we have described the transcriptome characteristics of normoweight and overweight/obese PCOS endometria. Our results indicate different endometrial gene expressions between different subtypes of PCOS and non-PCOS women, which might affect endometrial functions in PCOS patients.

Background: MOBILE and ENHANCE were similarly designed randomized trials of walking-impaired adults with relapsing-remitting or progressive multiple sclerosis (MS) who received placebo or 10 mg prolonged-release (PR)-fampridine twice daily for 24 weeks. Both studies showed sustained and clinically meaningful improvement in broad measures of walking and balance over 24 weeks of PR-fampridine treatment. Objective: To evaluate the functional benefits and safety of PR-fampridine versus placebo using a post hoc integrated efficacy analysis of MOBILE and ENHANCE data. Methods: Data from the intention-to-treat (ITT) populations of MOBILE and ENHANCE studies were pooled in a post hoc analysis based on the following outcome measures: 12-item MS Walking Scale (MSWS-12), Timed Up and Go (TUG) speed, Berg Balance Scale (BBS), MS Impact Scale physical impact subscale (MSIS-29 PHYS), EQ-5D utility index score, visual analogue scale (VAS), and adverse events. The primary analysis was the proportion of people with MS (PwMS) with a mean improvement in MSWS-12 score (⩾8 points) from baseline over 24 weeks. A subgroup analysis based on baseline characteristics was performed. Findings: In the ITT population ( N = 765; PR-fampridine, n = 383; placebo, n = 382), a greater proportion of PR-fampridine–treated PwMS than placebo-treated PwMS achieved a clinically meaningful improvement in the MSWS-12 scale over 24 weeks (44.3% versus 33.0%; p

Abstract Temozolomide (TMZ)-resistance hampers the therapeutic efficacy of this drug for glioblastoma (GBM) treatment in clinic, and emerging evidences suggested that exosomes from GBM-derived stem cells (GSCs) contributed to this process, but the detailed mechanisms are still largely unknown. In the present study, we reported that GSCs derived programmed death-ligand 1 (PD-L1) containing exosomes activated AMPK/ULK1 pathway mediated protective autophagy enhanced TMZ-resistance in GBM in vitro and in vivo. Specifically, we noticed that continuous low-dose TMZ stimulation promoted GSCs generation and PD-L1 containing exosomes (PD-L1-ex) secretion in GBM cells, and that PD-L1-ex inhibited cell apoptosis and promoted cell autophagy to increased TMZ-resistance in GBM cells, which were reversed by co-treating cells with the autophagy inhibitor 3-methyladenine (3-MA). Consistently, upregulation of PD-L1 also increased TMZ-resistance in TS-GBM cells, and silencing of PD-L1 sensitized TR-GBM cells to TMZ. In addition, PD-L1-ex activated AMPK/ULK1 pathway to induce autophagy in TMZ treated GBM cells, and the inhibitors for AMPK (compound C) and ULK1 (SBI-0206965) promoted cell apoptosis in GBM cells co-treated with PD-L1-ex and high-dose TMZ. Finally, we evidenced that PD-L1-ex promoted tumor growth and Ki67 protein expressions to increase TMZ-resistance in GBM in vivo. Collectively, we concluded that GSCs-derived PD-L1-ex activated AMPK1/ULK1 signaling cascade mediated autophagy to increase TMZ-resistance in GBM, and this study provided potential strategies to improve the therapeutic efficacy of TMZ in GBM.

Groundwater is an important source of drinking water, particularly in arid regions. In this study, a total of 66 groundwater samples were collected from the phreatic aquifer in the Shizuishan area, a traditional irrigation region of Ningxia. The results showed that the TDS values were above the drinking water standards for nearly 50% of the groundwater samples. The ions followed the order of Na+ > Ca2+ > Mg2+ > K+ and SO42− > Cl− > HCO3− in the groundwater. There were four dominant factors in controlling groundwater chemistry based on principal component analysis: the salinity factor, alkalinity factor, carbonate factor, and pollution factor. The high concentration of NH4-N in groundwater was attributed to agricultural activities, but the high NO3-N levels were mainly due to sewage or wastewater. F and As were derived from geogenic sources. Based on the result of the WQI assessment, about 40% of the samples in the central part of the study region showed unacceptable water quality for drinking, which was mainly associated with high NH4-N, TDS, and As concentrations. The total non-carcinogenic risks of drinking the groundwater were 0.05–10.62 for adults and 0.09–20.65 for children, respectively. The order of pollutants in the groundwater in terms of their hazard to residents was: As > F− > NO3-N > NH4-N. The carcinogenic risk values of As through oral ingestion for children and adults were 0–7.37 × 10−4 and 0–1.89 × 10−4, respectively. Chronic exposure by oral ingestion presented as the main source of susceptibility to exposure to groundwater contaminants for children.

With increasing consumption of energy and increasing environmental pollution, research on capturing the vibration energy lost during transportation and vehicle driving is growing rapidly. There is a large amount of vibration energy in the automobile exhaust system that can be recycled. This paper proposes a self-powered intelligent device (SPID) using a piezoelectric energy generator. The SPID includes a piezoelectric generator and sensor unit, and the generator is installed at the end of the automobile exhaust system. The generator adopts a parallel structure of four piezoelectric power generation units, and the sensing unit comprises light-emitting diode warning lights or low-power sensors. A simulated excitation experiment verifies the working state and peak power of the piezoelectric generator unit, which can achieve 23.4 μW peak power. The self-power supply and signal monitoring functions of the intelligent device are verified in experiments conducted for driving light-emitting diode lights and low-power sensors. The device is expected to play a crucial role in the field of intelligent driving and automobile intelligence.