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Abstract Background Sepsis is a potentially fatal systemic inflammatory response syndrome (SIRS) that threatens millions of lives worldwide. Echinococcus granulosus antigen B (EgAgB) is a protein released by the larvae of the tapeworm. This protein has been shown to play an important role in modulating host immune response. In this study we expressed EgAgB as soluble recombinant protein in E. coli (rEgAgB) and explored its protective effect on sepsis. Methods The sepsis model was established by cecal ligation and puncture (CLP) procedure in BALB/c mice. The therapeutic effect of rEgAgB on sepsis was performed by interperitoneally injecting 5 µg rEgAgB in mice with CLP-induced sepsis and observing the 72 h survival rate after onset of sepsis. The proinflammatory cytokines [tumor necrosis factor (TNF)-α, interleukin (IL)-6] and regulatory cytokines [IL-10, transforming growth factor beta (TGF-β)] were measured in sera, and the histopathological change was observed in livers, kidneys, and lungs of septic mice treated with rEgAgB compared with untreated mice. The effect of rEgAgB on the macrophage polarization was performed in vitro by incubating rEgAgB with peritoneal macrophages. The levels of TLR2 and MyD88 were measured in these tissues to determine the involvement of TLR-2/MyD88 in the sepsis-induced inflammatory signaling pathway. Results In vivo, we observed that treatment with rEgAgB significantly increased the survival rate of mice with CLP-induced sepsis up to 72 h while all mice without treatment died within the same period. The increased survival was associated with reduced pathological damage in key organs such as liver, lung, and kidneys. It was supported by the reduced proinflammatory cytokine levels and increased regulatory cytokine expression in peripheral blood and key organ tissues. Further study identified that treatment with rEgAgB promoted macrophage polarization from classically activated macrophage (M1) to regulatory M2-like macrophage via inhibiting TLR2/MyD88 signal pathway. Conclusions The therapeutic effects of rEgAgB on mice with sepsis was observed in a mice model that was associated with reduced inflammatory responses and increased regulatory responses, possibly through inducing polarization of macrophages from proinflammatory M1 to regulatory M2 phenotype through inhibiting TLR2/MyD88 inflammatory pathway. Graphical Abstract

Abstract Aims To investigate (1) the association between maternal dietary choices during the first and second trimesters and the diagnosis of gestational diabetes mellitus (GDM), (2) the association between a GDM diagnosis and dietary choices during pregnancy, and (3) the differences in pregnancy outcomes between individuals with and without GDM. Methods A prospective cohort study. Pregnant individuals with singleton pregnancy aged 19 ∼ 44 years, without severe pregnancy complications were enrolled in the study. Dietary data were collected at three time points during routine antenatal appointments: 8 ∼ 12 weeks gestation(n = 993), 20 ∼ 24 weeks gestation(n = 732), and 32 ∼ 36 weeks gestation(n = 536). GDM diagnosis and pregnancy outcomes were collected during follow-up from the electronic medical record (EMR). Results A total of 93 participants (12.9%) were diagnosed with GDM. Livestock and poultry meat intake during the second trimester were associated with an increased risk of developing GDM (aOR 1.371, 95%CI 1.070–1.756, P = 0.013), and a GDM diagnosis may lead to decreased intake of cereals and its products (P = 0.001), potatoes and its products (P

Abstract Land hermit crabs are a group of shell-carrying crabs that have evolved remarkable terrestrial adaptations in behavior, morphology, physiology, and biochemistry. However, the genetic mechanisms underlying these adaptations remain unclear. In addition, usually it is very difficult to get good genome assemblies for crustaceans. In this study, we managed to assemble the first chromosome-level genome for a land hermit crab (Coenobita brevimanus) with careful manual curation. The final assembly spans 4.74 Gb, with the contig N50 of 1.75 Mb and scaffold N50 of 42.95 Mb, encompassing 117 chromosomes that account for 96.54% of the genome. The evaluations including genome BUSCO (95.26%), Merqury qv (35.88) and the mapping ratio of pair-end short reads (99.48%) showed the high-continuity of C. brevimanus genome assembly, making it the genome with the highest quality in crustaceans with genome size bigger than 3 Gb. The availability of this chromosome-scale genome of crustaceans represents a valuable resource for the land hermit crab, which represents an independent water-to-land transition evolutionary event in the animal kingdom.

Abstract To assess the psychological and physiological benefits of early exercise rehabilitation in patients with acute coronary syndrome (ACS). Among 559 ACS-diagnosed patients at Fuzhou University Affiliated Provincial Hospital from January to December 2021, 200 eligible participants were assigned to two groups. The control group received standard care, while the experimental group received early exercise rehabilitation in addition to standard care. The outcomes measured included changes in depression levels (PHQ-9), fasting blood glucose, and troponin I (TnI) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels. Data were analyzed using SPSS, with t tests and chi-square tests for group comparisons. In comparison to the control group, the experimental group demonstrated significant improvements in PHQ-9 scores (P 0.05). Subgroup analysis revealed enhanced outcomes in the intervention group for ACS patients without smoking or drinking history and no heart failure (P = 0.025,P = 0.014,P = 0.018). Early exercise rehabilitation has notable benefits for ACS patients, including reduced depression, improved blood glucose control, and enhanced myocardial protection, especially in nondiabetic NSTEMI patients aged 60 and above.

Abstract Necroptosis and ferroptosis are two distinct forms of necrotic-like cell death in terms of their morphological features and regulatory mechanisms. These two types of cell death can coexist in disease and contribute to pathological processes. Inhibition of both necroptosis and ferroptosis has been shown to enhance therapeutic effects in treating complex necrosis-related diseases. However, targeting both necroptosis and ferroptosis by a single compound can be challenging, as these two forms of cell death involve distinct molecular pathways. In this study, we discovered that KW-2449, a previously described necroptosis inhibitor, also prevented ferroptosis both in vitro and in vivo. Mechanistically, KW-2449 inhibited ferroptosis by targeting the autophagy pathway. We further identified that KW-2449 functioned as a ULK1 (Unc-51-like kinase 1) inhibitor to block ULK1 kinase activity in autophagy. Remarkably, we found that Necrostatin-1, a classic necroptosis inhibitor that has been shown to prevent ferroptosis, also targets the autophagy pathway to suppress ferroptosis. This study provides the first understanding of how necroptosis inhibitors can prevent ferroptosis and suggests that autophagy is a targetable pathway for necroptosis inhibitors to prevent ferroptosis. Therefore, the identification and design of pharmaceutical molecules that target the autophagy pathway from necroptosis inhibitors is a promising strategy to develop dual inhibitors of necroptosis and ferroptosis in clinical application.

Abstract Background The development of modern agriculture has significantly contributed to improving global food security and safety, alleviating poverty, and enhancing human health and livelihoods. However, the rapid advancement of modern agriculture has also brought about various challenges that limit its sustainable development. This commentary aims to discuss these issues through the One Health lens, and provide valuable insights for balancing modern agricultural activities with the need to protect and promote the health of all the sectors. Main text This commentary explores the multifaceted impacts of modern agriculture on social development, as well as the associated various health challenges and environmental impacts within the One Health framework. Key issues include ecosystem degradation, increased risk of interspecies disease transmission like zoonoses, reverse zoonoses, and vector-borne diseases, and the escalated threat of antimicrobial resistance due to intensified agricultural production and increased antimicrobial use. To address these challenges, this commentary outlines potential solutions anchored in the development and implementation of modern technologies and good agricultural practices, such as precision farming, integrated pest management, biosecurity measures, vaccination programs, as well as surveillance and early detection of health risks. Conclusions Good agricultural practices supported by scientific and technological advancements are essential for aligning productivity with the One Health vision, ensuring the health and resilience of all the sectors. Enhancing stakeholder education, strengthening regulatory frameworks, and providing supportive policies and infrastructure for farmers to adopt sustainable practices are crucial for the long-term viability of agrifood systems. The Food and Agriculture Organization of the United Nations plays a pivotal role in guiding this sustainable transformation through the One Health approach.

Abstract Background Congenital optic disc pit (ODP) is a relatively uncommon congenital anomaly of the optic disc, which seriously affects the patient’s vision when combined with optic disc pit maculopathy(ODP-M). Currently, the treatment of ODP-M remains a clinical challenge and a focus of research. Case presentation A boy had a pit in the inferotemporal segment of the optic disc with ODP-M. Optical Coherence Tomography(OCT) showed ODP and serous retinal detachment. He was treated with pars plana vitrectomy(PPV), followed by Corneal Stromal Lenticule (CSL) sealing and C3F8 tamponade. In the end, significant anatomical improvement was achieved, and the Best Corrected Visual Acuity(BCVA) was improved. Conclusions The CSL transplantation may be a viable therapeutic option for improving ODP-M with stable anatomical and functional result. However, more cases and longer follow-up are needed to confirm the safety and effectiveness of the technology.

Purpose: Explore the causal relationship between the gut microbiota and erectile dysfunction (ED) at phylum, class, order, family, and genus levels, and identify specific pathogenic bacteria that may be associated with the onset and progression of ED. Materials and Methods: The genetic variation data of 196 human gut microbiota incorporated in our study came from the human gut microbiome Genome Wide Association Studies (GWAS) dataset released by the MiBioGen Consortium. The GWAS statistics for ED were extracted from one study by Bovijn et al., which included 223,805 participants of European ancestry, of whom 6,175 were diagnosed with ED. Subsequently, Mendelian randomization (MR) analysis was carried out to explore whether a causal relationship exists between the gut microbiota and ED. Additionally, bidirectional MR analysis was performed to examine the directionality of the causal relationship. Results: Through MR analysis, we found that family Lachnospiraceae (odds ratio [OR]: 1.27, 95% confidence interval [CI]: 1.05–1.52, p=0.01) and its subclass genus LachnospiraceaeNC2004 group (OR: 1.17, 95% CI: 1.01–1.37, p=0.04) are associated with a higher risk of ED. In addition, genus Oscillibacter (OR: 1.17, 95% CI: 1.02–1.35, p=0.03), genus Senegalimassilia (OR: 1.32, 95% CI: 1.06–1.64, p=0.01) and genus Tyzzerella3 (OR: 1.14, 95% CI: 1.02–1.27, p=0.02) also increase the risk of ED. In contrast, the inverse variance weighted estimate of genus RuminococcaceaeUCG013 (OR: 0.77, 95% CI: 0.61–0.96, p=0.02) suggests that it has a protective effect against the occurrence of ED. Conclusions: This study preliminarily identified 6 bacterial taxa that may have a causal relationship with ED, including family Lachnospiraceae, genus Lachnospiraceae NC2004 group, Oscillibacter, Senegalimassilia, Tyzzerella 3 and Ruminococcaceae UCG013. These identified important bacterial taxa may serve as candidates for microbiome intervention in future ED clinical trials.

Verticillium dahliae is an important fungal pathogen affecting cotton yield and quality. Therefore, the mining of V. dahlia-resistance genes is urgently needed. Proteases and protease inhibitors play crucial roles in plant defense responses. However, the functions and regulatory mechanisms of the protease inhibitor PR6 gene family remain largely unknown. This study provides a comprehensive analysis of the PR6 gene family in the cotton genome. We performed genome-wide identification and functional characterization of the cotton GhPR6 gene family, which belongs to the potato protease inhibitor I family of inhibitors. Thirty-nine PR6s were identified in Gossypium arboreum, G. raimondii, G. barbadense, and G. hirsutum, and they were clustered into four groups. Based on the analysis of pathogen-induced and Ghlmm transcriptome data, GhPR6-5b was identified as the key gene for V. dahliae resistance. Virus-induced gene silencing experiments revealed that cotton was more sensitive to V. dahliae V991 after PR6-5b silencing. The present study established that GhWRKY75 plays an important role in resistance to Verticillium wilt in cotton by positively regulating GhPR6-5b expression by directly binding to the W-box TTGAC(T/C). Our findings established that GhWRKY75 is a potential candidate for improving cotton resistance to V. dahliae, and provide primary information for further investigations and the development of specific strategies to bolster the defense mechanisms of cotton against V. dahliae.

In this study, the effect of Bangia fusco-purpurea polysaccharide (BFP) on Escherichia coli adhesion to Caco-2 monolayers and its potential mechanism was studied using an in vitro human colon adenocarcinoma cell (Caco-2) monolayer model. The effect of BFP on the adhesion of E. coli to Caco-2 monolayers was analyzed by fluorescence labeling with carboxyfluorescein diacetate and succinimidyl ester (CFDA-SE), and its effect on the gene expression of integrin β1 in Caco-2 cells, the adhesin FimH in E. coli, and inflammatory factors (IL-1β, IL-8 and TNF-α) induced by E. coli adhesion to Caco-2 cells and the tight junction proteins zonula occludens 1 (ZO-1) and occludin were analyzed using real-time polymerase chain reaction (real-time PCR). Also, the protein expression of ZO-1 and occludin in Caco-2 monolayers was detected using Western Blot analysis. Our results showed that BFP at concentrations of 400–800 μg/mL significantly inhibited the adhesion of E. coli to Caco-2 monolayers mainly by down-regulating the gene expression of integrin β1 in Caco-2 cells and FimH in E. coli. In addition, BFP significantly inhibited the up-regulation of inflammatory cytokine gene expression and the down-regulation of ZO-1 and occludin protein and gene expression induced by in Caco-2 cells induced by E. coli and its culture supernatant. In conclusion, BFP inhibited the adhesion of E. coli to Caco-2 cell monolayers, which will lay a scientific basis for the development of novel antimicrobial products and the high-value utilization and deep processing of BFP.

In this study, the complete mitochondrial genome (mitogenome) of Cotylorhiza tuberculata (Scyphozoa; Rhizostomeae; Cepheidae) was assembled by the next-generation sequencing data. The complete mitogenome spanned 16,590 bp and contained 14 protein-coding genes, two transfer RNA genes, and two ribosomal RNA genes. Total AT% content was 67.7%, comprising A 30.22%, C 16.16%, G 17.05%, and T 36.56%. The gene arrangement exhibited consistency with the known mitogenomes of other jellyfish species. Furthermore, the phylogenetic relationship of C. tuberculata was investigated based on analysis of the 13 common protein-coding genes. Results indicated a close relationship between C. tuberculata and both Cassiopea xamachana and Cassiopea andromeda. These findings provide a valuable reference for advancing understanding of the phylogenetic relationships, taxonomic classification, and phylogeography of jellyfish species.

Abstract Although the critical path method (CPM) is effective for the integrated scheduling of small-batch orders, its overemphasis on vertical process relationships and neglect of horizontal parallel relationships have imposed limitations on scheduling, often leading to suboptimal outcomes in terms of the total product completion time. This study introduces an innovative algorithm designed to overcome these limitations and further optimize the total processing time of products. We propose a strategy of "exchanging adjacent processes on the same device", which operates based on the scheduling results of the CPM. By swapping adjacent and interchangeable processes within the constraints of the problem, this algorithm generates multiple new scheduling schemes, effectively expanding the solution space. This expansion enables the discovery of optimized solutions that leverage "horizontal parallel relationships", which is crucial for reducing the "total processing time of products". Finally, the effectiveness of the proposed algorithm is verified through experiments.

AIM: To evaluate the clinical effect of a new surgery technique (covering corneal stromal lenticule, CSL) for macular hole (MH) in pathological myopia. METHODS: This was a prospective non-randomized series case study. Fourteen eyes of 14 patients whose axial length were more than 29 mm and suffered from MH and macular hole retinal detachment (MHRD) were included in this study. All cases were treated with 25-gauge pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peeling, covering CSL and C3F8 gas tamponade. These cases were followed for 6mo, and the best-corrected visual acuity (BCVA), healing status of MH, the reattached rate of retinal detachment (RD), and reoperation rate were analyzed. RESULTS: All cases were successfully performed the surgery and the postoperative follow-up was completed. After surgery, MHs were healed in all 14 eyes (100%, 14/14) after assessed by optical coherence tomography. The reattachment of retina was achieved in all 6 eyes (100%, 6/6) with MHRD. BCVA was improved in 12 eyes (85.71%, 12/14), and had no significant change in 2 eyes (14.29%, 2/14). The overall mean BCVA was improved from 1.80±0.77 to 0.82±0.46 logMAR (F=10.46, P

Background: Soil salinization is one of the key factors restricting the production of cropland. Once rice is subjected to alkali stress at the bud burst stage, the yield will suffer irreparable serious loss. Compared with salt tolerance, studies on QTL mapping and candidate gene analysis of rice alkali tolerance are limited. Results: In this study, we used the F2:3 population derived from the alkali-tolerant cultivar LD21 and the alkali-sensitive cultivar WL138 to construct an alkali-tolerant DNA mixing pool, and the BSA (Bulked Segregation Analysis) method was used for re-sequencing. The main QTL qRSLB9 controlling the relative shoot length of rice under alkali stress was mapped by QTL-seq. The candidate interval was narrowed to 346.5 kb by regional linkage mapping, which containing 6 DEGs screened through transcriptome sequencing. The qRT-PCR and candidate gene sequencing showed that LOC_Os09g24260 was most likely to control relative shoot length (RSL) in rice as a major gene who encodes the WD domain, G-beta repeat domain-containing protein. Conclusions: Based on these results, LOC_Os09g24260 was the candidate gene of qRSLB9 conferring alkalinity tolerance to rice at the bud burst stage. Our study provides valuable genetic information and materials for breeding new rice varieties with alkalinity tolerance.How to cite: Wang J, Bian J, Liu L, et al. Screening and analysis of candidate genes conferring alkalinity tolerance in rice (Oryza sativa L.) at the bud burst stage based on QTL-seq and RNA-seq. Electron J Biotechnol 2024;71. https://doi.org/10.1016/j.ejbt.2024.07.002.

Abstract Brucella spp. are facultative intracellular pathogens that cause zoonosis- brucellosis worldwide. There has been a trend of the re-emergence of brucellosis worldwide in recent years. The epidemic situation of brucellosis is serious in Xinjiang. To analyze the epidemic situation of Brucella spp. in Xinjiang among humans and animals, this study identified 144 Brucella isolates from Xinjiang using classical identification and 16 S rRNA sequencing. MLVA, drug resistance testing, and wgSNP detection were also performed. At the same time, analysis was conducted based on the published data of Brucella isolates worldwide. The results showed that the dominant species was B. melitensis biovar 3, which belonged to GT42 (MLVA-8 typing) and the East Mediterranean lineage. The correlation among isolates was high both in humans or animals. The isolates in Xinjiang exhibited higher polymorphism compared to other locations in China, with polymorphism increasing each year since 2010. No amikacin/kanamycin-resistant strains were detected, but six rifampicin-intermediate isolates were identified without rpoB gene variation. The NJ tree of the wgSNP results indicated that there were three main complexes of the B. melitensis epidemic in Xinjiang. Based on the results of this study, the prevention and control of brucellosis in Xinjiang should focus on B. melitensis, particularly strains belonging to B. melitensis bv.3 GT42 (MLVA-8 typing) and East Mediterranean lineage. Additionally, the rifampicin- and trimethoprim-sulfamethoxazole- resistance of isolates in Xinjiang should be closely monitored to avoid compromising the therapeutic efficacy and causing greater losses. These results provide essential data for the prevention and control of brucellosis in Xinjiang and China. Although the isolates from Xinjiang have significant characteristics among Chinese isolates and can reflect the epidemiological situation of brucellosis in China to some extent, this study cannot represent the characteristics of isolates from other regions.

Abstract One of the main drivers of autism spectrum disorder is risk alleles within hundreds of genes, which may interact within shared but unknown protein complexes. Here we develop a scalable genome-editing-mediated approach to target 14 high-confidence autism risk genes within the mouse brain for proximity-based endogenous proteomics, achieving the identification of high-specificity spatial proteomes. The resulting native proximity proteomes are enriched for human genes dysregulated in the brain of autistic individuals, and reveal proximity interactions between proteins from high-confidence risk genes with those of lower-confidence that may provide new avenues to prioritize genetic risk. Importantly, the datasets are enriched for shared cellular functions and genetic interactions that may underlie the condition. We test this notion by spatial proteomics and CRISPR-based regulation of expression in two autism models, demonstrating functional interactions that modulate mechanisms of their dysregulation. Together, these results reveal native proteome networks in vivo relevant to autism, providing new inroads for understanding and manipulating the cellular drivers underpinning its etiology.

Abstract Background Spinal cord injury (SCI) is characterized by extensive demyelination and inflammatory responses. Facilitating the clearance of lipid droplets (LDs) within microglia contributes to creating a microenvironment that favors neural recovery and provides essential materials for subsequent remyelination. Therefore, investigating MicroRNAs (miRNAs) that regulate lipid homeostasis after SCI and elucidating their potential mechanisms in promoting LDs clearance in microglia have become focal points of SCI research. Methods We established a subacute C5 hemicontusion SCI model in mice and performed transcriptomic sequencing on the injury epicenter to identify differentially expressed genes and associated pathways. Confocal imaging was employed to observe LDs accumulation. Multi-omics analyses were conducted to identify differentially expressed mRNA and miRNA post-SCI. Pathway enrichment analysis and protein-protein interaction network construction were performed using bioinformatics methods, revealing miR-223-Abca1 as a crucial miRNA-mRNA pair in lipid metabolism regulation. BV2 microglia cell lines overexpressing miR-223 were engineered, and immunofluorescence staining, western blot, and other techniques were employed to assess LDs accumulation, relevant targets, and inflammatory factor expression, confirming its role in regulating lipid homeostasis in microglia. Results Histopathological results of our hemicontusion SCI model confirmed LDs aggregation at the injury epicenter, predominantly within microglia. Our transcriptomic analysis during the subacute phase of SCI in mice implicated ATP-binding cassette transporter A1 (Abca1) as a pivotal gene in lipid homeostasis, cholesterol efflux and microglial activation. Integrative mRNA-miRNA multi-omics analysis highlighted the crucial role of miR-223 in the neuroinflammation process following SCI, potentially through the regulation of lipid metabolism via Abca1. In vitro experiments using BV2 cells overexpressing miR-223 demonstrated that elevated levels of miR-223 enhance ABCA1 expression in myelin debris and LPS-induced BV2 cells. This promotes myelin debris degradation and LDs clearance, and induces a shift toward an anti-inflammatory M2 phenotype. Conclusions In summary, our study unveils the critical regulatory role of miR-223 in lipid homeostasis following SCI. The mechanism by which this occurs involves the upregulation of ABCA1 expression, which facilitates LDs clearance and myelin debris degradation, consequently alleviating the lipid burden, and inhibiting inflammatory polarization of microglia. These findings suggest that strategies to enhance miR-223 expression and target ABCA1, thereby augmenting LDs clearance, may emerge as appealing new clinical targets for SCI treatment.

Abstract Background Although men with premature ejaculation (PE) always show more negative emotions, including embarrassment, guilt and worry, this may be related to the stigma of PE. To investigated stigma and its associations with self-confidence and sexual relations in 4 PE syndromes, a survey was conducted in our hospital from December 2018 to December 2019 among 350 men with self-reported PE and 252 men without self-reported PE. The stigma, self-confidence and sexual relations were assessed by the Social Impact Scale (SIS) and Self-Esteem and Relationship questionnaire (SEAR), respectively. Ejaculation control, sexual life satisfaction and distress caused by PE were evaluated by the Index of PE. Results Men with self-reported PE had higher internalized shame and social isolation scores and lower SEAR scores than control subjects. The highest score of internalized shame and social isolation and the lowest score of SEAR appeared in men with lifelong PE (LPE). After age adjustment, the positive relationships were stronger between distress about PE and internalized shame. Whereas, the stronger negative associations were found between social isolation and sexual satisfaction. The strongest association was observed between social isolation and sexual relationship. Therefore, the stigma associated with PE adversely affects the self-confidence, self-esteem, and sexual relationships of men with PE. Conclusion Men with PE, especially LPE, have a high level of stigma and disharmonious sexual relations, and often lack self-confidence and self-esteem, which have a certain negative impact on their physical and mental health and life. These will be the key issues to be considered when we formulate a personalized treatment plan for PE.

Abstract There is a growing body of evidence suggesting that Hashimoto’s thyroiditis (HT) may contribute to an increased risk of papillary thyroid carcinoma (PTC). However, the exact relationship between HT and PTC is still not fully understood. The objective of this study was to identify potential common biomarkers that may be associated with both PTC and HT. Three microarray datasets from the GEO database and RNA-seq dataset from TCGA database were collected to identify shared differentially expressed genes (DEGs) between HT and PTC. A total of 101 genes was identified as common DEGs, primarily enriched inflammation- and immune-related pathways through GO and KEGG analysis. We performed protein–protein interaction analysis and identified six significant modules comprising a total of 29 genes. Subsequently, tree hub genes (CD53, FCER1G, TYROBP) were selected using random forest (RF) algorithms for the development of three diagnostic models. The artificial neural network (ANN) model demonstrates superior performance. Notably, CD53 exerted the greatest influence on the ANN model output. We analyzed the protein expressions of the three genes using the Human Protein Atlas database. Moreover, we observed various dysregulated immune cells that were significantly associated with the hub genes through immune infiltration analysis. Immunofluorescence staining confirmed the differential expression of CD53, FCER1G, and TYROBP, as well as the results of immune infiltration analysis. Lastly, we hypothesise that benzylpenicilloyl polylysine and aspirinmay be effective in the treatment of HT and PTC and may prevent HT carcinogenesis. This study indicates that CD53, FCER1G, and TYROBP play a role in the development of HT and PTC, and may contribute to the progression of HT to PTC. These hub genes could potentially serve as diagnostic markers and therapeutic targets for PTC and HT.

Abstract Objective Shift work and Shift Work Sleep Disorder (SWSD) are known to affect the secretion of several neurotransmitters and hormones associated with premature ejaculation (PE). However, their specific influence on the regulation of male ejaculation remains unclear. This study explores the relationship between shift work, SWSD, and PE. Methods From April to October 2023, a cross-sectional survey was conducted across five regions of China to explore the work schedules, sleep quality, and sexual function of male workers. Participants' sleep quality was evaluated using a validated SWSD questionnaire, and their erectile function and ejaculatory control were assessed with the International Inventory of Erectile Function (IIEF-5) scores and Premature Ejaculation Diagnostic Tool (PEDT) scores, respectively. Univariate and multivariate linear regression analyses were employed to identify risk factors associated with PE. Confounders were controlled using multiple regression models, and clinical prediction models were developed to predict PE onset and assess the contribution of risk factors. Results The study included 1239 eligible participants, comprising 840 non-shift workers and 399 shift workers (148 with SWSD and 251 without SWSD). Compared to non-shift working males, those involved in shift work (β 1.58, 95% CI 0.75 – 2.42, p

Abstract Background Autism Spectrum Disorder (ASD) is a group of neurodevelopmental disorders with higher incidence in males and is characterized by atypical verbal/nonverbal communication, restricted interests that can be accompanied by repetitive behavior, and disturbances in social behavior. This study investigated brain mechanisms that contribute to sociability deficits and sex differences in an ASD animal model. Methods Sociability was measured in C58/J and C57BL/6J mice using the 3-chamber social choice test. Bulk RNA-Seq and snRNA-Seq identified transcriptional changes in C58/J and C57BL/6J amygdala within which DMRseq was used to measure differentially methylated regions in amygdala. Results C58/J mice displayed divergent social strata in the 3-chamber test. Transcriptional and pathway signatures revealed immune-related biological processes differ between C58/J and C57BL/6J amygdala. Hypermethylated and hypomethylated genes were identified in C58/J versus C57BL/6J amygdala. snRNA-Seq data in C58/J amygdala identified differential transcriptional signatures within oligodendrocytes and microglia characterized by increased ASD risk gene expression and predicted impaired myelination that was dependent on sex and sociability. RNA velocity, gene regulatory network, and cell communication analysis showed diminished oligodendrocyte/microglia differentiation. Findings were verified using Bulk RNA-Seq and demonstrated oxytocin’s beneficial effects on myelin gene expression. Limitations Our findings are significant. However, limitations can be noted. The cellular mechanisms linking reduced oligodendrocyte differentiation and reduced myelination to an ASD phenotype in C58/J mice need further investigation. Additional snRNA-Seq and spatial studies would determine if effects in oligodendrocytes/microglia are unique to amygdala or if this occurs in other brain regions. Oxytocin’s effects need further examination to understand its’ potential as an ASD therapeutic. Conclusions Our work demonstrates the C58/J mouse model’s utility in evaluating the influence of sex and sociability on the transcriptome in concomitant brain regions involved in ASD. Our single-nucleus transcriptome analysis elucidates potential pathological roles of oligodendrocytes and microglia in ASD. This investigation provides details regarding regulatory features disrupted in these cell types, including transcriptional gene dysregulation, aberrant cell differentiation, altered gene regulatory networks, and changes to key pathways that promote microglia/oligodendrocyte differentiation. Our studies provide insight into interactions between genetic risk and epigenetic processes associated with divergent affiliative behavior and lack of positive sociability.

Abstract Background Lipid droplet (LD)-laden microglia is a key pathological hallmark of multiple sclerosis. The recent discovery of this novel microglial subtype, lipid-droplet-accumulating microglia (LDAM), is notable for increased inflammatory factor secretion and diminished phagocytic capability. Lipophagy, the autophagy-mediated selective degradation of LDs, plays a critical role in this context. This study investigated the involvement of microRNAs (miRNAs) in lipophagy during demyelinating diseases, assessed their capacity to modulate LDAM subtypes, and elucidated the potential underlying mechanisms involved. Methods C57BL/6 mice were used for in vivo experiments. Two weeks post demyelination induction at cervical level 4 (C4), histological assessments and confocal imaging were performed to examine LD accumulation in microglia within the lesion site. Autophagic changes were observed using transmission electron microscopy. miRNA and mRNA multi-omics analyses identified differentially expressed miRNAs and mRNAs under demyelinating conditions and the related autophagy target genes. The role of miR-223 in lipophagy under these conditions was specifically explored. In vitro studies, including miR-223 upregulation in BV2 cells via lentiviral infection, validated the bioinformatics findings. Immunofluorescence staining was used to measure LD accumulation, autophagy levels, target gene expression, and inflammatory mediator levels to elucidate the mechanisms of action of miR-223 in LDAM. Results Oil Red O staining and confocal imaging revealed substantial LD accumulation in the demyelinated spinal cord. Transmission electron microscopy revealed increased numbers of autophagic vacuoles at the injury site. Multi-omics analysis revealed miR-223 as a crucial regulatory gene in lipophagy during demyelination. It was identified that cathepsin B (CTSB) targets miR-223 in autophagy to integrate miRNA, mRNA, and autophagy gene databases. In vitro, miR-223 upregulation suppressed CTSB expression in BV2 cells, augmented autophagy, alleviated LD accumulation, and decreased the expression of the inflammatory mediator IL-1β. Conclusion These findings indicate that miR-223 plays a pivotal role in lipophagy under demyelinating conditions. By inhibiting CTSB, miR-223 promotes selective LD degradation, thereby reducing the lipid burden and inflammatory phenotype in LDAM. This study broadens the understanding of the molecular mechanisms of lipophagy and proposes lipophagy induction as a potential therapeutic approach to mitigate inflammatory responses in demyelinating diseases.

Abstract The development and aging of the brain constitute a lifelong dynamic process, marked by structural and functional changes that entail highly coordinated cellular differentiation and epigenetic regulatory mechanisms. Chromatin accessibility serves as the foundational basis for genetic activity. However, the holistic and dynamic chromatin landscape that spans various brain regions throughout development and ageing remains predominantly unexplored. In this study, we employed single-nucleus ATAC-seq to generate comprehensive chromatin accessibility maps, incorporating data from 69,178 cells obtained from four distinct brain regions – namely, the olfactory bulb (OB), cerebellum (CB), prefrontal cortex (PFC), and hippocampus (HP) – across key developmental time points at 7 P, 3 M, 12 M, and 18 M. We delineated the distribution of cell types across different age stages and brain regions, providing insight into chromatin accessible regions and key transcription factors specific to different cell types. Our data contribute to understanding the epigenetic basis of the formation of different brain regions, providing a dynamic landscape and comprehensive resource for revealing gene regulatory programs during brain development and aging.

IntroductionIn the pursuit of agricultural sustainability and food security, the stability of livestock production under large-scale operations plays a pivotal role.MethodsBased on panel data from 26 provinces in China spanning the years 2007 to 2020, this study employs a two-way panel fixed effects model to examine the stabilizing effect of scale breeding on swine production volatility in China. Additionally, it utilizes the moderating effect model to examine the moderating effect of epidemic risk and policy intervention, and uses the threshold effect model to test the threshold effect of marketization level.ResultsEmpirical evidence indicates that moderate-scale breeding exerts a stabilizing effect on swine production volatility, with this effect displaying regional disparities. From the external situation, the higher the risk of epidemic disease, the stronger the stable effect of scale breeding on the fluctuation of swine production, while the enhancement of policy intervention cannot promote the stability of scale breeding on swine production volatility. There is a single threshold effect on the impact of scale breeding on swine production volatility. When the degree of marketization reaches a certain level, the stabilizing effect of scale breeding on swine production volatility is enhanced.DiscussionTherefore, it is recommended to promote the moderately scaled swine breeding, enhance epidemic monitoring and information disclosure systems, reduce excessive policy intervention, and fully leverage the self-regulating role of the market.

Summary: Group 2 innate lymphoid cells (ILC2s) are key players in type 2 immunity, but whether they can be directly activated by microbial ligands remain uncertain. In this study, we observed a positive correlation between blood endotoxin (LPS) levels and circulating ILC2s in allergic patients. In vitro, LPS robustly induced ILC2 proliferation and production of type 2 effector cytokines. RNA-seq revealed a type 2 immune-responsive profile in LPS-stimulated ILC2s. Notably, ILC2s lost their LPS-mediated growth and activation capacity when treated with TLR4 receptor antagonists and inhibitors of the NF-κB and JAK pathways, though this effect was not observed with IL-33 receptor blocking antibodies. Genetically, ILC2s from TLR4 knockout (KO) mice, but not from ST2 KO mice, were unresponsive to LPS. Collectively, these findings suggest a direct, non-canonical activation mechanism of ILC2s via the LPS-TLR4-NF-κB/JAK signaling axis.

The severe conditions at high altitudes, where yaks inhabit, contribute to delayed muscular growth and compromised tenderness of their muscle tissue. Myosatellite cells are responsible for the growth and regeneration of skeletal muscle after birth and have the potential to proliferate and differentiate, its development is closely related to meat quality, and the nuclear receptor gene NR1D1 is involved in muscle formation and skeletal muscle regulation. Therefore, in order to understand the effect of NR1D1 on muscle satellite cells, we identified the mRNA expression levels of marker genes specifically expressed in muscle satellite cells at different stages to determine the type of cells isolated. Eventually, we successfully constructed a primary cell line of yak muscle satellite cells. Then we constructed NR1D1 overexpression vector and interference RNA, and introduced them into isolated yak skeletal muscle satellite cells. We performed qPCR, CCK8, and fluorescence-specific to detect the expression of genes or abundance of proteins as markers of cell proliferation and differentiation. Compared with those in the control group, the expression levels of proliferation marker genes KI-67, CYCLIND1, and CYCLINA were significantly inhibited after NR1D1 overexpression, which was also supported by the CCK-8 test, whereas differentiation marker genes MYOD, MYOG, and MYF5 were significantly inhibited. Fluorescence-specific staining showed that KI-67 protein abundance and the number of microfilaments both decreased, while the opposite trend was observed after NR1D1 interference. In conclusion, we confirmed that NR1D1 inhibited the proliferation and differentiation of yak skeletal muscle satellite cells, which provides a theoretical basis for further research on the effect of NR1D1 on improving meat quality traits and meat production performance of yaks.

The purpose of this study was to develop a nomogram using hemogram inflammatory markers to predict the risk of infertility in patients with varicocele (VC). Patients with VC from March 2022 to June 2024 were retrospectively investigated. We divided the patients into two groups based on their fertility status. A total of 162 patients were enrolled: 81 in the infertile group and 81 in the fertile group. Statistical differences were observed between the two groups in lymphocyte, monocyte, erythrocyte, red cell distribution width (RDW), mean erythrocyte volume (MCV), mean platelet volume (MPV), platelet distribution width (PDW), neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), MPV/platelet ratio (MPVPR), and systemic inflammation response index (SIRI) ( p < .05). The 162 patients were divided into a modeling cohort and a validation cohort in a 7:3 ratio. A predictive nomogram was constructed based on independent influencing factors identified through univariate and multivariate logistic regression analyses. Receiver operating characteristic curve analysis, calibration curve, and decision curve analysis were used to assess the model’s performance. Multivariate logistic regression analysis indicated that erythrocyte count, PDW, NLR, and SIRI were independent influencing factors. The area under the curve for the nomogram predicting the risk of infertility in patients with VC was 0.869 in the validation cohort. The nomogram demonstrated good predictive performance. In this study, we developed an effective predictive nomogram for assessing the risk of infertility in VC patients using inflammatory markers. However, further external validation is crucial.

Ejaculatory duct obstruction (EDO) is a rare but treatable cause of male infertility. This case report describes a 28-year-old male with obstructive azoospermia. The patient came to our hospital after a fertility check-up revealed azoospermia. A subsequent semen analysis confirmed azoospermia. Transrectal ultrasonography (TRUS) and magnetic resonance imaging (MRI) revealed bilaterally enlarged seminal vesicles and thickened, calcified ejaculatory duct walls. The patient underwent transurethral seminal vesiculoscopy and transurethral resection of the ejaculatory ducts (TURED) for presumed partial EDO. Despite two transurethral seminal vesiculoscopy and TURED procedures, postoperative semen analysis still showed azoospermia. TRUS indicated non-contractile seminal vesicles and an unobstructed ejaculatory duct. The patient ultimately underwent percutaneous epididymal sperm aspiration for assisted reproductive technology and his spouse got pregnant. We identified a case of azoospermia caused by a rare combination of partial and functional ejaculatory duct obstruction. There are currently no reports of similar cases. This case report aims to provide valuable insights for diagnosing and treating EDO.

Summary: Background: While microplastics are widely found in various human organs and tissues, the relationship between microplastics and human health, especially prostate health, remains unclear. This study aims to identify and quantify the properties, types, and abundance of microplastics in paired para-tumor and tumor tissues of human prostate. Additionally, the potential correlation between microplastics abundance and prostate cancer are investigated. Methods: Paired para-tumor and tumor samples of the prostate were collected from 22 patients who underwent robot-assisted radical prostatectomy. A combination of laser direct infrared spectroscopy, scanning electron microscopy and pyrolysis-gas chromatography-mass spectrometry was utilized to analyse the properties, type and abundance of microplastics. Correlations between microplastics abundance, demographic characteristics and clinical features of patients were also examined. Findings: Laser direct infrared analysis revealed the presence of microplastics, including polyamide, polyethylene terephthalate, and polyvinyl chloride, in both para-tumor and tumor tissues of human prostate. However, polystyrene was exclusively detected in tumor tissues. The particle size distribution in the prostate tissue mainly ranged from 20 to 100 μm. Approximately 31.58% of para-tumor samples exhibited sizes between 20 and 30 μm, while 35.21% of tumor samples displayed sizes between 50 and 100 μm. The shapes of these microplastics varied considerably with irregular forms being predominant. Additionally, microplastics were detected by pyrolysis–gas chromatography-mass spectrometry in 20 paired prostate tissues. The mean abundance of microplastics was found to be 181.0 μg/g and 290.3 μg/g in para-tumor and tumor of human prostate samples, respectively. Among the 11 target types microplastics polymers, only polystyrene, polypropylene, polyethylene, and polyvinyl chloride were detected. Notably, polystyrene, polyethylene, and polyvinyl chloride, except for polypropylene, demonstrated significantly higher abundance in tumor tissues compared to their respective paired para-tumor. Furthermore, a positive correlation was observed between polystyrene abundance in the tumor samples of human prostate and frequency of take-out food consumption. Interpretation: This research provides both qualitative and quantitative evidence of the microplastics presence as well as their properties, types, and abundance in paired para-tumor and tumor samples of human prostate. Correlations between microplastics abundance, demographics, and clinical characteristics of patients need to be further validated in future studies with a larger sample size. Funding: This work was supported by the National Key Research and Development Program of China (2022YFC2702600) and the National Natural Science Foundation of China (Grant No. 82071698, No. 82101676, and No. 82271630).

Varicocele (VC) is the most frequent and reversible cause of male infertility. One of the preferred management strategies to alleviate this problem is varicocelectomy. However, there are no researchers who have explored the relationship between better timing and postoperative sperm DNA fragmentation index (DFI) improvement in patients. We conducted this meta-analysis by enrolling published studies to find out the best waiting time after varicocelectomy to wait for better improvement of sperm DFI. A literature search was conducted using PubMed, Embase, Scopus, Web of Science, and Cochrane Library databases. The data from the pooled analysis were presented as mean difference (MD) along with a 95% confidence interval (CI). Heterogeneity was evaluated using I 2 . Four studies were included after screening relevant literature. Statistical analysis revealed that after varicocelectomy, follow-up results within 3 months showed a significant improvement in sperm DFI compared with the preoperative period (MD: –3.66, 95% CI = [–5.17, –2.14], p < .00001), and follow-up results with 6 months showed a significant improvement in sperm DFI compared with the postoperative 3 months as well (MD: –1.51, 95% CI = [–2.73, –0.29], p = .02). Notably, no further improvement in sperm DFI was observed when the follow-up period reached 12 months (MD: –1.59, 95% CI = [–3.22, 0.05], p = .06). Six months after varicocelectomy may be the optimal time for sperm DFI compared with 12 months or even longer, which means it is also the preferable time for conception. However, more well-designed prospective studies are needed in the future to validate our conclusion.

Summary: Cryptorchidism, commonly known as undescended testis, affects 1%–9% of male newborns, posing infertility and testis tumor risks. Despite its prevalence, the detailed pathophysiology underlying male infertility within cryptorchidism remains unclear. Here, we profile and analyze 46,644 single-cell transcriptomes from individual testicular cells obtained from adult males diagnosed with cryptorchidism and healthy controls. Spermatogenesis compromise in cryptorchidism links primarily to spermatogonium self-renewal and differentiation dysfunctions. We illuminate the involvement of testicular somatic cells, including immune cells, thereby unveiling the activation and degranulation of mast cells in cryptorchidism. Mast cells are identified as contributors to interstitial fibrosis via transforming growth factor β1 (TGF-β1) and cathepsin G secretion. Furthermore, significantly increased levels of secretory proteins indicate mast cell activation and testicular fibrosis in the seminal plasma of individuals with cryptorchidism compared to controls. These insights serve as valuable translational references, enriching our comprehension of testicular pathogenesis and informing more precise diagnosis and targeted therapeutic strategies for cryptorchidism.

Pelvic fracture is a serious injury, which has a profound impact on sexual function due to concurrent nervous and urethral injuries. In this case report, we describe a 29-year-old single man who had retrograde ejaculation as a result of a pelvic fracture-related posterior urethral stricture. The patient wanted to improve his ejaculatory ability after experiencing urethral stricture for 8 years and retrograde ejaculation for 3 years following the pelvic fracture. We precisely located and measured the patient’s urethral stricture using a retrograde urethrogram, and we used transrectal color Doppler ultrasound to track the patient’s ejaculation process in real time. Next, we used urethral balloon dilatation to relieve the urethral stricture. Urinary obstruction symptoms have completely resolved, and the patient was able to urinate without any obstructions. Meanwhile, the real-time transrectal color Doppler ultrasound result showed that some semen might ejaculate externally by passing through the initial stricture area, while some semen continued to flow retrogradely into the bladder.

AimThis study aimed to evaluate the operational efficiency of traditional Chinese medicine (TCM) hospitals in China.MethodsPearson’s analysis was used to test the correlation between the input and output variables. Data envelopment analysis (DEA) was utilized to analyze the input and output variables of 16 TCM hospitals, and each hospital efficiency score was computed by Deap 2.1, assuming variable return to scale (VRS), which is an input-oriented model. t tests were conducted to confirm the significant difference of efficiency scores at the hospital level and by hospital type, and ANOVA was used to test for significant differences in efficiency scores according to hospitals’ size.ResultsThe correlation coefficient of the input and output indicators was between 0.613 and 0.956 (p 0.05).ConclusionThis study revealed that tertiary TCM hospitals had a greater level of efficiency than secondary TCM hospitals. In our study, 50% of TCM hospitals had inefficient management. Therefore, to activate the new development power of TCM hospitals, it is necessary to reform and improve the management system and mechanism of TCM hospitals, optimize the development environment of TCM hospitals and formulate development plans and measures based on local conditions.

BackgroundAs a novel indicator of inflammation, the relationship between the systemic immune-inflammation index (SIRI) and mortality in patients with asthma remains uncertain. Our study aimed to explore the association between SIRI and mortality in asthma patients.MethodsData from the National Health and Nutrition Examination Survey (NHANES) for US adults from 2001 to 2018 were included in this study. Then, we divided all patients into three groups based on SIRI tertiles and used multivariable weighted Cox regression analysis, smoothing curve fitting, survival curve analysis, and subgroup analysis to investigate the relationship between SIRI and asthma.ResultsA total of 6,156 participants were included in the study, with each SIRI tertile consisting of 2052 individuals. Asthma patients with higher SIRI levels were older, had a higher level of education, were more likely to be married, and had a higher chance of being smokers. In Cox proportional-hazards models, the highest SIRI group showed higher hazard ratios (HRs) for all-cause mortality in individuals with asthma after adjusting for potential confounders. The restricted cubic spline analysis indicated a non-linear relationship between SIRI and all-cause mortality. The Kaplan–Meier survival curves showed that patients with higher SIRI levels had a higher risk of all-cause mortality. Subgroup analyses revealed SIRI’s association with all-cause mortality across various demographics, including age, sex, race, education levels, smoking status, and marital status.ConclusionOur study provides evidence for the relationship between SIRI and mortality in asthma patients. SIRI may potentially serve as a predictive tool for evaluating asthma mortality rates.

The long-term safety and effectiveness of once-daily tadalafil is crucial, but limited data are available in Chinese patients with erectile dysfunction (ED). In this post-marketing, multicenter, randomized, open-label trial with 2-year follow-up, 635 ED cases were randomized to receive daily oral tadalafil 2.5 mg or 5 mg for 3 months, of whom 580 continued once-daily tadalafil 5 mg for 21 months. Treatment-emergent adverse events in the 12-month and 24-month period were similar, with the most common being viral upper respiratory tract infection, upper respiratory tract infection, and headache. Significant improvement from baseline in the International Index of Erectile Function-Erectile Function (IIEF-EF) score was detected at month 12 (least squares mean [LSM] change: 7.9, 95% confidence interval [CI]: 7.5–8.4, P < 0.001) and was maintained to month 24 (LSM change: 8.6, 95% CI: 8.1–9.0, P < 0.001). The proportions of patients regaining normal erectile function (IIEF-EF score ≥26) were 43.7% and 48.0% at months 12 and 24, respectively. Global Assessment Questionnaire results showed improved erection function in 97.5% of patients and improved ability to engage in sexual activity in 95.9% of patients at month 12; these values were 96.1% and 95.0% at month 24, respectively. The quality of sexual life score based on the Sexual Life Quality Questionnaire (SLQQ) was increased by 52.2% at month 12 and by 55.3% at month 24 (both P < 0.001). The treatment satisfaction score determined by SLQQ (mean ± standard deviation) was 62.4 ± 21.0 at month 12 versus 65.9 ± 20.2 at month 24. Two-year daily application of tadalafil 5 mg in Chinese men with ED showed a favorable safety profile and durable improvement in sexual performance and satisfaction.

Background and purpose: Long noncoding RNA (lncRNA) can regulate gene transcription, mRNA shear, stabilization and translation, and it is an important regulatory factor in a variety of biological processes. This study aimed to investigate the expression and clinical features of lncRNA FLJ30679 in oral squamous cell carcinoma (OSCC) and its effect on the malignant biological behavior of OSCC. Methods: The expression of FLJ30679 in head and neck squamous cell carcinoma (HNSCC) tissues and normal tissues was analyzed by the UCSC Xena database for expression and prognosis. The expression of FLJ30679 in OSCC cell lines was detected by real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR). The subcellular localization of FLJ30679 in OSCC cells was detected by RNA nuclear-cytoplasmic fractionation assays. FLJ30679 Smart Silencer was used to establish the FLJ30679 knockdown group (SS-FLJ30679), and overexpression plasmid of FLJ30679 was used to establish FLJ30679 overexpression group (FLJ30679). The effects of altered FLJ30679 expression on the proliferative and migration capacity of OSCC cells were examined by cell counting kit-8 (CCK-8) and transwell migration assays. RTFQ-PCR and Western blot were used to determine the effect of altered FLJ30679 expression on the expression of epithelial-mesenchymal transition (EMT)-related genes in OSCC cells. The effects of altered FLJ30679 expression on the phosphoinositide 3-kinase (PI3K)/protein kinase (AKT) pathway were detected by Western blot. Results: Online query of database showed that FLJ30679 expression was higher in HNSCC tissues compared to normal tissues (P

Abstract Background Acute ischemic stroke (AIS) is one of the most common cerebrovascular diseases which accompanied by a disruption of aminothiols homeostasis. To explore the relationship of aminothiols with neurologic impairment severity, we investigated four aminothiols, homocysteine (Hcy), cysteine (Cys), cysteinylglycine (CG) and glutathione (GSH) in plasma and its influence on ischemic stroke severity in AIS patients. Methods A total of 150 clinical samples from AIS patients were selected for our study. The concentrations of free reduced Hcy (Hcy), own oxidized Hcy (HHcy), free reduced Cys (Cys), own oxidized Cys (cysteine, Cyss), free reduced CG (CG) and free reduced GSH (GSH) were measured by our previously developed hollow fiber centrifugal ultrafiltration (HFCF-UF) method coupled with high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The concentration ratio of Hcy to HHcy (Hcy/HHcy), Cys to Cyss (Cys/Cyss) were also calculated. The neurologic impairment severity of AIS was evaluated using National Institutes of Health Stroke Scale (NIHSS). The Spearman correlation coefficient and logistic regression analysis was used to estimate and perform the correlation between Hcy, HHcy, Cys, Cyss, CG, GSH, Hcy/HHcy, Cys/Cyss and total Hcy with NIHSS score. Results The reduced Hcy and Hcy/HHcy was both negatively correlated with NIHSS score in AIS patients with P = 0.008, r=-0.215 and P = 0.002, r=-0.249, respectively. There was no significant correlation of Cys, CG, GSH, HHcy, Cyss, Cys/Cyss and total Hcy with NIHSS score in AIS patients with P value > 0.05. Conclusions The reduced Hcy and Hcy/HHcy, not total Hcy concentration should be used to evaluate neurologic impairment severity of AIS patient.

To characterize the chromosomes of the four species of Polygonatum Miller, 1754, used in traditional Chinese medicine, P. cyrtonema Hua, 1892, P. kingianum Collett et Hemsley, 1890, P. odoratum (Miller, 1768) Druce, 1906, and P. sibiricum Redouté, 1811, and have an insight into the karyotype variation of the genus Polygonatum, fluorescence in situ hybridization (FISH) with 5S and 45S rDNA oligonucleotide probes was applied to analyze the karyotypes of 9 populations of the four species. Detailed molecular cytogenetic karyotypes of the 9 populations were established for the first time using the dataset of chromosome measurements and FISH signals of 5S and 45S rDNA. Four karyotype asymmetry indices, CVCI, CVCL, MCA and Stebbins’ category, were measured to elucidate the asymmetry of the karyotypes and karyological relationships among species. Comparison of their karyotypes revealed distinct variations in the karyotypic parameters and rDNA patterns among and within species. The basic chromosome numbers detected were x = 9, 11 and 13 for P. cyrtonema, x = 15 for P. kingianum, x = 10 and 11 for P. odoratum, and x = 12 for P. sibiricum. The original basic chromosome numbers of the four species were inferred on the basis of the data of this study and previous reports. All the 9 karyotypes were of moderate asymmetry and composed of metacentric, submetacentric and subtelocentric chromosomes or consisted of two of these types of chromosomes. Seven populations have one locus of 5S rDNA and two loci of 45S rDNA, and two populations added one 5S or 45S locus. The karyological relationships among the four species revealed by comparison of rDNA patterns and PCoA based on x, 2n, TCL, CVCI, MCA and CVCL were basically accordant with the phylogenetic relationships revealed by molecular phylogenetic studies. The mechanisms of both intra- and inter-specific dysploidy in Polygonatum were discussed based on the data of this study and literature.

Abstract Background Decitabine (DAC), a DNA methyltransferase inhibitor, has shown efficacy combined with chemotherapy for relapsed or refractory (R/R) acute myeloid leukemia (AML) in adults, but less is known about its efficacy in children. Accordingly, we conducted a study which involved a priming regimen consisting of DAC with cladribine, cytarabine, and granulocyte-stimulating factor (DAC-CLAG) and compared the efficacy and safety of this regimen with CLAG alone. Methods A total of 39 R/R AML children who received the CLAG or DAC-CLAG regimen in Shanghai Children’s Hospital were retrospectively enrolled in this non-randomized study. These regimens were studied sequentially over time. Twenty-two patients received CLAG from 2015, while 17 patients were administered epigenetic priming with DAC before CLAG from 2020. Patients were subsequently bridged to stem cell transplantation (SCT) or consolidation chemotherapy. Complete remission (CR) and adverse effects were analyzed by Fisher’s exact test, and survival was analyzed by the Kaplan–Meier method. Results DAC-CLAG conferred a numerically higher CR compared to CLAG (70.59% vs 63.64%; P = 0.740). High CR rates occurred in patients with good cytogenetics (P = 0.029) and prior induction without cladribine (P = 0.099). The 1-year event-free survival (EFS) was 64.71% ± 11.59% and 63.31% ± 10.35% in the DAC-CLAG and CLAG group (P = 0.595), and 1-year overall survival (OS) was 81.45% ± 9.72% and 77.01% ± 9.04%, respectively (P = 0.265). The 1-year OS and EFS after SCT were higher in the DAC-CLAG than in the CLAG cohort (100% vs 92.31% ± 7.39%, P = 0.072; 92.31% ± 7.39% vs 85.71% ± 9.35%, P = 0.158). Univariate analysis revealed that a good prognosis included good cytogenetics (P = 0.002), non-complex karyotype (P = 0.056), CR on reinduction (P

Abstract Background Patients with immunocompromise were suspected to encounter a high risk for severe coronavirus disease 2019 (COVID-19) infection on early period; however, data is lacking nowadays and immune response remain unclear. Methods In this retrospective study, internet questionnaire survey and medical records were acquired in pediatric hematology oncology patients. Clinical severity, immunological characteristics, and outcomes were analyzed from December 1, 2022 to January 31, 2023 at the 3rd year of pandemic in China. Results A total of 306 patients were included, with 21 patients (6.9%) asymptomatic, 262 (85.6%) mild severity, 17 (5.6%) moderate severity, 5 (1.6%) severe severity, and 1 (0.3%) critical severity. Seventy-eight (25.5%) patients were on intensive chemotherapy, and 32.0% children were on maintenance chemotherapy. Delays in cancer therapy occurred in 86.7% patients. Univariable analysis revealed active chemotherapy (P