The dysfunction of CD8+ T cells triggered by endometriotic stromal cells promotes the immune survival of endometriosis.

Endometriosis is defined as an oestrogen-dependent and inflammatory gynaecological disease of which the pathogenesis remains unclear. This study aimed to investigate the cellular heterogeneity and reveal the effect of CD8+ T cells on the progress of endometriosis. Three ovarian endometriosis patients were collected, and single-cell RNA sequencing (scRNA-seq) progressed and delineated the cellular landscape of endometriosis containing five cell clusters. The endometrial cells (EMCs) were the major component, of which the mesenchymal cells were preponderant and characterized with increased inflammation and oestrogen synthesis in endometriosis. The proportion of T cells, mainly CD8+ T cells rather than CD4+, was reduced in endometriotic lesions, and the cytokines and cytotoxicity of ectopic T cells were depressed. CD8+ T cells depressed the proliferation of ESCs through inhibiting CDK1/CCNB1 pathway to arrest the cell cycle and triggered inflammation through activating STAT1 pathway. Correspondingly, the coculture with ESCs resulted in the dysfunction of CD8+ T cells through upregulating STAT1/PDCD1 pathway and glycolysis-promoted metabolism reprogramming. The endometriotic lesions were larger in nude mouse models with T-cell deficiency than the normal mouse models. The inhibition of T cells via CD90.2 or CD8A antibody increased the endometriotic lesions in mouse models, and the supplement of T cells to nude mouse models diminished the lesion sizes. In conclusion, this study revealed the global cellular variation of endometriosis among which the cellular count and physiology of EMCs and T cells were significantly changed. The depressed cytotoxicity and aberrant metabolism of CD8+ T cells were induced by ESCs with the activation of STAT1/PDCD1 pathway resulting in immune survival to promote endometriosis.

Tumor Microenvironment Specific Regulation Ca-Fe-Nanospheres for Ferroptosis-Promoted Domino Synergistic Therapy and Tumor Immune Response.

Reactive oxygen species (ROS)-mediated emerging treatments exhibit unique advantages in cancer therapy in recent years. While the efficacy of ROS-involved tumor therapy is greatly restricted by complex tumor microenvironment (TME). Herein, a dual-metal CaO2@CDs-Fe (CCF) nanosphere, with TME response and regulation capabilities, are proposed to improve ROS lethal power by a multiple cascade synergistic therapeutic strategy with domino effect. In response to weak acidic TME, CCF will decompose, accompanied with intracellular Ca2+ upregulated and abundant H2O2 and O2 produced to reverse antitherapeutic TME. Then the exposed CF cores can act as both Fenton agent and sonosensitizer to generate excessive ROS in the regulated TME for enhanced synergistic CDT/SDT. In combination with calcium overloading, the augmented ROS induced oxidative stress will cause more severe mitochondrial damage and cellular apoptosis. Furthermore, CCF can also reduce GPX4 expression and enlarge the lipid peroxidation, causing ferroptosis and apoptosis in parallel. These signals of damage will finally initiate damage-associated molecular patterns to activate immune response and to realize excellent antitumor effect. This outstanding domino ROS/calcium loading synergistic effect endows CCF with excellent anticancer effect to efficiently eliminate tumor by apoptosis/ferroptosis/ICD both in vitro and in vivo.

Localized High-Concentration Sulfone Electrolytes with High-Voltage Stability and Flame Retardancy for Ni-Rich Lithium Metal Batteries.

The localized high-concentration electrolyte (LHCE) propels the advanced high-voltage battery system. Sulfone-based LHCE is a transformative direction compatible with high energy density and high safety. In this work, the application of lithium bis(trifluoromethanesulphonyl)imide and lithium bis(fluorosulfonyl)imide (LiFSI) in the LHCE system constructed from sulfolane and 1,1,2,2-tetrafluoroethyl-2,2,3,3-tetrafluoropropyl ether (TTE) is investigated. The addition of diluent causes an increase of contact ion pairs and ionic aggregates in the solvation cluster and an acceptable quantity of free solvent molecules. A small amount of LiFSI as an additive can synergistically decompose with TTE on the cathode and participate in the construction of both electrode interfaces. The designed electrolyte helps the Ni-rich system to cycle firmly at a high voltage of 4.5 V. Even with high mass load and lean electrolyte, it can keep a reversible specific capacity of 91.5% after 50 cycles. The constructed sulfone-based electrolyte system exhibits excellent thermal stability far beyond the commercial electrolytes. Further exploration of in-situ gelation has led to a quick conversion of the designed liquid electrolyte to the gel state, accompanied by preserved stability, which provides a direction for the synergistic development of LHCE with gel electrolytes.

Parallel evolution of morphological and genomic selfing syndromes accompany the breakdown of heterostyly.

Evolutionary transitions from outcrossing to selfing in flowering plants have convergent morphological and genomic signatures and can involve parallel evolution within related lineages. Adaptive evolution of morphological traits is often assumed to evolve faster than nonadaptive features of the genomic selfing syndrome. We investigated phenotypic and genomic changes associated with transitions from distyly to homostyly in the Primula oreodoxa complex. We determined whether the transition to selfing occurred more than once and investigated stages in the evolution of morphological and genomic selfing syndromes using 22 floral traits and both nuclear and plastid genomic data from 25 populations. Two independent transitions were detected representing an earlier and a more recently derived selfing lineage. The older lineage exhibited classic features of the morphological and genomic selfing syndrome. Although features of both selfing syndromes were less developed in the younger selfing lineage, they exhibited parallel development with the older selfing lineage. This finding contrasts with the prediction that some genomic changes should lag behind adaptive changes to morphological traits. Our findings highlight the value of comparative studies on the timing and extent of transitions from outcrossing to selfing between related lineages for investigating the tempo of morphological and molecular evolution.

Pectin demethylation-mediated cell wall Na+ retention positively regulates salt stress tolerance in oilseed rape.

KEY MESSAGE: Integrated phenomics, ionomics, genomics, transcriptomics, and functional analyses present novel insights into the role of pectin demethylation-mediated cell wall Na+ retention in positively regulating salt tolerance in oilseed rape. Genetic variations in salt stress tolerance identified in rapeseed genotypes highlight the complicated regulatory mechanisms. Westar is ubiquitously used as a transgenic receptor cultivar, while ZS11 is widely grown as a high-production and good-quality cultivar. In this study, Westar was found to outperform ZS11 under salt stress. Through cell component isolation, non-invasive micro-test, X-ray energy spectrum analysis, and ionomic profile characterization, pectin demethylation-mediated cell wall Na+ retention was proposed to be a major regulator responsible for differential salt tolerance between Westar and ZS11. Integrated analyses of genome-wide DNA variations, differential expression profiling, and gene co-expression networks identified BnaC9.PME47, encoding a pectin methylesterase, as a positive regulator conferring salt tolerance in rapeseed. BnaC9.PME47, located in two reported QTL regions for salt tolerance, was strongly induced by salt stress and localized on the cell wall. Natural variation of the promoter regions conferred higher expression of BnaC9.PME47 in Westar than in several salt-sensitive rapeseed genotypes. Loss of function of AtPME47 resulted in the hypersensitivity of Arabidopsis plants to salt stress. The integrated multiomics analyses revealed novel insights into pectin demethylation-mediated cell wall Na+ retention in regulating differential salt tolerance in allotetraploid rapeseed genotypes. Furthermore, these analyses have provided key information regarding the rapid dissection of quantitative trait genes responsible for nutrient stress tolerance in plant species with complex genomes.

Obesity and lipid indices as predictors of depressive symptoms in middle-aged and elderly Chinese: insights from a nationwide cohort study.

BACKGROUND: Depressive symptoms are one of the most common psychiatric disorders, with a high lifetime prevalence rate among middle-aged and elderly Chinese. Obesity may be one of the risk factors for depressive symptoms, but there is currently no consensus on this view. Therefore, we investigate the relationship and predictive ability of 13 obesity- and lipid-related indices with depressive symptoms among middle-aged and elderly Chinese. METHODS: The data were obtained from The China Health and Retirement Longitudinal Study (CHARLS). Our analysis includes individuals who did not have depressive symptoms at the baseline of the CHARLS Wave 2011 study and were successfully follow-up in 2013 and 2015. Finally, 3790 participants were included in the short-term (from 2011 to 2013), and 3660 participants were included in the long-term (from 2011 to 2015). The average age of participants in short-term and long-term was 58.47 years and 57.88 years. The anthropometric indicators used in this analysis included non-invasive [e.g. waist circumference (WC), body mass index (BMI), and a body mass index (ABSI)], and invasive anthropometric indicators [e.g. lipid accumulation product (LAP), triglyceride glucose index (TyG index), and its-related indices (e.g. TyG-BMI, and TyG-WC)]. Receiver operating characteristic (ROC) analysis was used to examine the predictive ability of various indicators for depressive symptoms. The association of depressive symptoms with various indicators was calculated using binary logistic regression. RESULTS: The overall incidence of depressive symptoms was 20.79% in the short-term and 27.43% in the long-term. In males, WC [AUC = 0.452], LAP [AUC = 0.450], and TyG-WC [AUC = 0.451] were weak predictors of depressive symptoms during the short-term (P < 0.05). In females, BMI [AUC = 0.468], LAP [AUC = 0.468], and TyG index [AUC = 0.466] were weak predictors of depressive symptoms during the long-term (P < 0.05). However, ABSI cannot predict depressive symptoms in males and females during both periods (P > 0.05). CONCLUSION: The research indicates that in the middle-aged and elderly Chinese, most obesity- and lipid-related indices have statistical significance in predicting depressive symptoms, but the accuracy of these indicators in prediction is relatively low and may not be practical predictors.

Umbilical artery thrombosis risk factors and perinatal outcomes.

PURPOSE: The purpose of this study was to investigate the risk factors for umbilical artery thrombosis (UAT) and the relationship between umbilical artery thrombosis and perinatal outcomes. METHODS: This was a retrospective study that enrolled singleton pregnant women who were diagnosed with umbilical artery thrombosis. The control group recruited pregnant woman with three umbilical vessels or those with isolated single umbilical artery (iSUA) who were matched with umbilical artery thrombosis group. The risk factors and perinatal outcomes were compared between the groups. RESULTS: Preconception BMI (OR [95%CI]: 1.212 [1.038-1.416]), abnormal umbilical cord insertion (OR [95%CI]: 16.695 [1.333-209.177]) and thrombophilia (OR [95%CI]: 15.840 [1.112-223.699]) were statistically significant risk factors for umbilical artery thrombosis. An elongated prothrombin time (OR [95%CI]: 2.069[1.091-3.924]) was strongly associated with the occurrence of UAT. The risks of cesarean delivery, preterm birth, fetal growth restriction, neonatal asphyxia, and intraamniotic infection were higher in pregnancies with UAT than in pregnancies with three umbilical vessels or isolated single umbilical artery (P<0.05). Additionally, the incidence of thrombophilia was higher in pregnant women with umbilical artery thrombosis than those with isolated single umbilical artery (P = 0.032). Abnormal umbilical cord insertion was also found to be associated with an elevated risk of iSUA (OR [95%CI]: 15.043[1.750-129.334]). CONCLUSIONS: Abnormal umbilical cord insertion was the risk factor for both umbilical artery thrombosis and isolated single umbilical artery. The pregnancies with umbilical artery thrombosis had a higher risk of the adverse perinatal outcomes.

Obesity-and lipid-related indices as a risk factor of hypertension in mid-aged and elderly Chinese: a cross-sectional study.

OBJECTIVE: Hypertension refers to the persistent elevation of blood pressure above the established normal range, resulting in increased pressure exerted by blood on the walls of blood vessels during its circulation. Recent studies have identified significant associations between obesity and lipid-related indices, as well as hypertension. Nevertheless, these studies have yet to comprehensively examine the correlation between the two variables. Our objective is to identify the fat and lipid-related indices that have the strongest correlation with hypertension. METHOD: There was a total of 9488 elderly and middle-aged Chinese citizens who participated in this investigation. The participants in this research were separated into distinct gender cohorts. The participants were classified into normal and hypertensive categories according to their gender, with hypertension defined as a blood pressure level of 140/90 mmHg or higher, or a history of hypertension. Through the utilization of binary logistic regression analyses and the receiver operator curve (ROC), the optimal among fourteen indicators associated with obesity and lipids were identified. RESULTS: After adjusting for variables, statistical analysis showed that all 14 measures of obesity and lipid were risk factors for hypertension. The receiver operating characteristic (ROC) curve analysis reveals that the Chinese visceral adiposity index (CVAI) has the highest degree of relationship to hypertension. Simultaneously, a statistically significant association between hypertension and these 14 variables was observed in both males and females. CONCLUSION: There was a significant independent association between various parameters related to obesity and lipid-related index and the presence of hypertension, indicating that these factors can be considered risk factors for hypertension. CVAI and WHtR (waist height ratio) can be used to screen the high-risk groups of hypertensions in middle-aged and elderly people in China, and then take individualized health care measures to reduce the harm of hypertension.

Methodologic Quality and Pharmacotherapy Recommendations for Patient Blood Management Guidelines for Cardiac Surgery on Cardiopulmonary Bypass.

Patient blood management (PBM) guidelines for patients undergoing cardiac surgery under cardiopulmonary bypass (CPB) have increased during the past decade, and pharmacotherapy plays an important role in PBM. In the face of the undefined consistency in the methodologic quality and pharmacotherapy recommendations across multiple guidelines, this study exclusively evaluated methodologies of the related guideline development process, and compiled medication recommendations of PBM for cardiac surgery patients. PBM guidelines for cardiac surgery under CPB were searched through some mainstream literature and guideline databases from database establishment to May 15, 2023. Nine guidelines meeting inclusion criteria were included in this study. The quality of the guidelines was evaluated using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool. "Stakeholder involvement" received the lowest mean score of 49.38% in the AGREE II scoring among the guidelines. PBM for cardiac surgery patients spans the perioperative phase. Drug therapy strategies of PBM for cardiac surgery patients involve anemia therapy, perioperative administration of antithrombotic drugs, intraoperative anticoagulation, and the use of hemostatic drugs. Unlike for adults, there is less evidence about the management of antithrombotic drugs and hemostatic drugs for pediatric cardiac surgery patients. Recombinant activated factor VII (rFVIIa) and desmopressin (DDAVP) are not recommended after pediatric cardiac surgery, whereas prothrombin complex concentrate could be considered in clinical trials. As for the controversies regarding the administration of rFVIIa and DDAVP after adult cardiac surgery by different societies, clinicians should exercise their clinical judgment based on individual patient features.

Novel PATL2 variants cause female infertility with oocyte maturation defect.

PURPOSE: Oocyte maturation defect (OOMD) is a rare cause of in vitro fertilization failure characterized by the production of immature oocytes. Compound heterozygous or homozygous PATL2 mutations have been associated with oocyte arrest at the germinal vesicle (GV), metaphase I (MI), and metaphase II (MII) stages, as well as morphological changes. METHODS: In this study, we recruited three OOMD cases and conducted a comprehensive multiplatform laboratory investigation. RESULTS: Whole exome sequence (WES) revealed four diagnostic variants in PATL2, nonsense mutation c.709C > T (p.R237*) and frameshift mutation c.1486_1487delinsT (p.A496Sfs*4) were novel mutations that have not been reported previously. Furthermore, the pathogenicity of these variants was predicted using in silico analysis, which indicated detrimental effects. Molecular dynamic analysis suggested that the A496S variant disrupted the hydrophobic segment, leading to structural changes that affected the overall protein folding and stability. Additionally, biochemical and molecular experiments were conducted on cells transfected with wild-type (WT) or mutant PATL2 (p.R237* and p.A496Sfs*4) plasmid vectors. CONCLUSIONS: The results demonstrated that PATL2A496Sfs*4 and PATL2R237* had impacts on protein size and expression level. Interestingly, expression levels of specific genes involved in oocyte maturation and early embryonic development were found to be simultaneously deregulated. The findings in our study expand the variation spectrum of the PATL2 gene, provide solid evidence for counseling on future pregnancies in affected families, strongly support the application of in the diagnosis of OOMD, and contribute to the understanding of PATL2 function.

[Clinical and genetic analysis of a patient with Baraitser-Winter syndrome due to variant of ACTG1 gene].

OBJECTIVE: To explore the clinical features and genetic etiology of a child with Baraitser-Winter syndrome (BWS). METHODS: A BWS child who had sought medical attention at the Linyi People's Hospital on April 8, 2022 was selected as the study subject. Clinical data of the child was collected, and peripheral blood samples were obtained from the child and his parents. Whole exome sequencing (WES) was carried out, and candidate variant was verified by Sanger sequencing and bioinformatic analysis. RESULTS: The child, a 5-year-and-6-month-old male, had typical clinical features of BWS including congenital non-myogenic ptosis, arched eyebrows, wide philtrum, and pointed chin. Neurological symptoms included microcephaly, developmental delay, epilepsy, and deafness. Cranial MRI revealed enlarged frontal lobes, decreased white matter, and hydrocephalus. WES has identified a heterozygous c.430G>A (p.Asn144Tyr) missense variant in the ACTG1 gene. Sanger sequencing confirmed that neither of his parents has carried the same variant. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as likely pathogenic (PS2+PM2_Supporting+PP3_Moderate+PP4). CONCLUSION: The heterozygous c.430G>A (p.Asn144Tyr) missense variant of the ACTG1 gene probably underlay the pathogenesis of BWS in this child. Above finding has enriched the mutation spectrum of BWS-related genes and provided a basis for clinical diagnosis and genetic counseling.

Role of toll-like receptors in the pathogenesis of COVID-19: Current and future perspectives.

The coronavirus disease 2019 (COVID-19) pandemic underlines a persistent threat of respiratory tract infectious diseases and warrants preparedness for a rapid response. At present, COVID-19 has had a serious social impact and imposed a heavy global burden on public health. The exact pathogenesis of COVID-19 has not been fully elucidated. Since the outbreak of COVID-19, a renewed attention has been brought to Toll-like receptors (TLRs). Available data and new findings have demonstrated that the interaction of human TLRs and SARS-CoV-2 is a vital mediator of COVID-19 immunopathogenesis. TLRs such as TLR2, 4, 7 and 8 are potentially important in viral combat and activation of immunity in patients with COVID-19. Therapeutics targeting TLRs are currently considered promising options against the pandemic. A number of TLR-targeting immunotherapeutics are now being investigated in preclinical studies and different phases of clinical trials. In addition, innovative vaccines based on TLRs under development could be a promising approach for building a new generation of vaccines to solve the current challenges. In this review, we summarize recent progress in the role of TLRs in COVID-19, focusing the new candidate drugs targeting TLRs, the current technology and potential paths forward for employing TLR agonists as vaccine adjuvants.

Metatranscriptomics revealed the molecular characterization of circulating enterovirus strains causing aseptic meningitis in children in Wuxi, China.

Enteroviruses are major etiological agents of aseptic meningitis globally, however information on circulating enterovirus types associated with this disease in Wuxi, China is limited. In this study, cerebrospinal fluid samples were collected from 20 pediatric aseptic meningitis cases in a Wuxi hospital in 2020 and subjected to metagenomic analysis to detect pathogens. Enterovirus B was detected in 9 cases, including 7 echovirus 18 (E18) and 2 echovirus 11 (E11) strains. The E18 strains exhibited 87.5-98.2% nucleotide identity and phylogenetically clustered with other China E18 strains, while the E11 strains showed 97.59% identity and clustered within the D5 subgroup along with other China E11 strains. One E18 strain was identified as a novel recombinants with a distinct recombination breakpoint within 3D gene. These findings expand knowledge on enteroviruses associated with pediatric aseptic meningitis in Wuxi, and highlight the circulation of genetically diverse E18 and E11 strains, including novel E18 recombinants. Characterization of enterovirus diversity by metagenomic analysis is important for molecular diagnosis and epidemiological tracking of aseptic meningitis cases. Continued surveillance of circulating enterovirus strains in Wuxi that may cause future outbreaks is warranted.

Satisfactory outcomes from the double-row fixation procedure for ankle lateral ligaments injury with os subfibulare.

Background: Ossicles of avulsed fractures of the lateral malleolus can result in pain or chronic ankle instability. The purpose of this study was to evaluate and compare the arthroscopic double-row fixation procedure with anatomic ankle lateral ligaments reconstruction for the treatment of ankle lateral ligaments injury with os subfibulare. Methods: This retrospective study included 38 patients with ankle lateral ligaments injury with concomitant os subfibulare who were treated between July 2016 and November 2021. The patients were divided into a double-row fixation group (n = 19) and an ankle lateral ligaments reconstruction group (n = 19). The Karlsson and Peterson Scoring System for Ankle Function (KAFS), American Orthopedic Foot and Ankle Society (AOFAS) score, Tegner score, visual analog scale (VAS), and anterior drawer test (ADT) were obtained preoperatively and at the last post-operative follow-up. Magnetic resonance imaging (MRI) was also performed at the last post-operative follow-up. Results: The KAFS, AOFAS, VAS, and Tegner scores increased significantly after the surgery. Furthermore, the pre- and post-operative functional scores were comparable between the two groups. The ADT was negative in all participants post-operatively. There were no significant differences between the double-row fixation and ligaments reconstruction groups regarding the proportions of patients who achieved a minimally clinically important difference (MCID) in KAFS, AOFAS, and Tegner scores. There was no significant difference in T2 mapping values for the tibial and talar side post-operatively between the two groups. Moreover, there were no significant differences in functional scores post-operatively between bony fusion and non-fusion patients in the double fixation group. Conclusion: The double-row fixation procedure provided similar satisfactory clinical outcomes when compared with lateral ligaments reconstruction for the treatment of ankle lateral ligaments injury with os subfibulare over a short follow-up duration.

A biomechanical comparison of the double-row suture fixation and compression screw techniques in the treatment of lateral malleolar avulsion fracture.

Background: Avulsion fractures of fibula occur with ankle sprains. The purpose of this study was to compare the biomechanical characteristics of double-row suture versus compression screw techniques in treatment of lateral malleolar avulsion fracturelarger than 10 mm in size, which is typically not associated with an anterior talofibular ligament injury. Methods: We simulated lateral malleolus avulsion fractures in six matched pairs of 12 human cadaveric ankles. These were then randomly divided into two groups: a double-row fixation group and a compression screw group. Biomechanical testing was performed after surgical fixation. The foot was rotated from the neutral position toward inversion at a rate of 1°/s until 12.5 N-m or structural failure was reached. The final rotation torque, rotation angle, stiffness, and displacement of the ossicles were recorded. Results: No significant difference was found in the final rotation torque (7.60 ± 3.70 vs 7.23 ± 2.06 N-m, p = 0.87), rotation angle (43.61 ± 14.77° vs 40.93 ± 10.94°, p = 0.56), stiffness (0.19 ± 0.08 vs 0.13 ± 0.07, p = 0.33), or displacement (6.11 ± 5.23 vs 7.09 ± 5.93 mm, p = 0.77) between the two groups. Conclusions: The stability of the double-row suture fixation was equivalent to compression screw fixation in treating a lateral malleolar avulsion fracture larger than 10 mm in size with ligament injury, as determined by our biomechanical testing.

Photocatalytic NO x removal and recovery: progress, challenges and future perspectives.

The excessive production of nitrogen oxides (NO x ) from energy production, agricultural activities, transportation, and other human activities remains a pressing issue in atmospheric environment management. NO x serves both as a significant pollutant and a potential feedstock for energy carriers. Photocatalytic technology for NO x removal and recovery has received widespread attention and has experienced rapid development in recent years owing to its environmental friendliness, mild reaction conditions, and high efficiency. This review systematically summarizes the recent advances in photocatalytic removal, encompassing NO x oxidation removal (including single and synergistic removal and NO3 - decomposition), NO x reduction to N2, and the emergent NO x upcycling into green ammonia. Special focus is given to the molecular understanding of the interfacial nitrogen-associated reaction mechanisms and their regulation pathways. Finally, the status and the challenges of photocatalytic NO x removal and recovery are critically discussed and future outlooks are proposed for their potential practical application.

Prevalence and Characteristics of Plasmid-Encoded Serine Protease EspP in Clinical Shiga Toxin-Producing Escherichia coli Strains from Patients in Sweden.

Shiga toxin-producing Escherichia coli (STEC) infection can cause a broad spectrum of symptoms spanning from asymptomatic shedding to mild and bloody diarrhea (BD) and even life-threatening hemolytic-uremic syndrome (HUS). As a member of the serine protease autotransporters of Enterobacteriaceae (SPATE) family, EspP has the ability to degrade human coagulation factor V, leading to mucosal bleeding, and also plays a role in bacteria adhesion to the surface of host cells. Here, we investigated the prevalence and genetic diversity of espP among clinical STEC isolates from patients with mild diarrhea, BD, and HUS, as well as from asymptomatic individuals, and assessed the presence of espP and its subtypes in correlation to disease severity. We found that 130 out of 239 (54.4%) clinical STEC strains were espP positive, and the presence of espP was significantly associated with BD, HUS, and O157:H7 serotype. Eighteen unique espP genotypes (GTs) were identified and categorized into four espP subtypes, i.e., espPα (119, 91.5%), espPγ (5, 3.8%), espPδ (4, 3.1%), and espPε (2, 1.5%). espPα was widely distributed, especially in strains from patients with BD and HUS, and correlated with serotype O157:H7. Serogroup O26, O145, O121, and O103 strains carried espPα only. Ten GTs were identified in espPα, and espPα/GT2 was significantly associated with severe disease, i.e., BD and HUS. Additionally, espP was strongly linked to the presence of eae gene, and the coexistence of espPα and stx2/stx2a + stx2c was closely related to HUS status. To sum up, our data demonstrated a high prevalence and genetic diversity of the espP gene in clinical STEC strains in Sweden and revealed an association between the presence of espP, espP subtypes, and disease severity. espP, particularly the espPα subtype, was prone to be present in more virulent STEC strains, e.g., "top-six" serotypes strains.

Development of composite functional tissue sheets using hiPSC-CMs and hADSCs to improve the cardiac function after myocardial infarction.

Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have been widely used in therapy of ischemic heart disease. However, there are still remaining issues that limit the therapeutic efficacy, such as immune rejection and low retention of hiPSC-CMs. Human adipose mesenchymal stromal cells (hADSCs) have been reported to be able to regulate the immune response, promote angiogenesis and promote the maturation of hiPSC-CMs. In this study, we co-cultured these two types of cells on fiber scaffold made of biodegradable poly (D,L-lactic-co-glycolic acid) (PLGA) polymer for several days to develop a composited 3D cardiac tissue sheet. As expected, the cells formed 231.00 ± 15.14 µm thickness tissue, with improved organization, alignment, ECM condition, contractile ability, and paracrine function compared to culture hiPSC-CMs only on PLGA fiber. Furthermore, the composited 3D cardiac tissue sheet significantly promoted the engraftment and survival after transplantation. The composited 3D cardiac tissue sheet also increased cardiac function, attenuated ventricular remodeling, decreased fibrosis, and enhanced angiogenesis in rat myocardial infarction model, indicating that this strategy wound be a promising therapeutic option in the clinical scenario.

The mediating effect of resilience and COVID-19 anxiety on the relationship between social support and insomnia among healthcare workers: a cross-sectional study.

Background: Insomnia in healthcare workers has become a topic of concern in the health system. The high infectivity and longevity of the COVID-19 pandemic have resulted in great pressure and a high incidence of insomnia among healthcare workers. Insomnia among healthcare workers has a negative impact on high-quality healthcare services in addition to their health. Thus, it's necessary to explore insomnia's underlying mechanisms. Object: The present research's aims were threefold: explored the association between social support, resilience, COVID-19 anxiety, and insomnia among healthcare workers during the pandemic, elucidated the underlying mechanism of insomnia, and offered recommendations for improving the health of these workers. Materials and methods: A cross-sectional design was adopted. From May 20 to 30, 2022, 1038 healthcare workers were selected to fill out the Oslo 3-item Social Support Scale, the eight-item Athens Insomnia Scale, the Coronavirus Anxiety Scale, and the Brief Resilience Scale. Descriptive statistics and correlations were analyzed by SPSS 25.0. Mediation analysis was conducted by Mplus 8.3 using 5000 bootstrap samples. Results: Of the participating 1038 healthcare workers, the prevalence of insomnia was 41.62% (432/1038). Significant associations were found involving insomnia, resilience, COVID-19 anxiety, and social support. Insomnia was directly affected by social support. Moreover, three indirect pathways explain how social support affected insomnia: resilience's mediating role, COVID-19 anxiety's mediating role, and the chain-mediation role of resilience and COVID-19 anxiety. Conclusion: The results validated our hypotheses and supported the opinion of Spielman et al. 's three-factor model of insomnia. Social support of healthcare workers has an indirect impact on insomnia in addition to its direct one via independent and chain-mediation effects of resilience and COVID-19 anxiety.

Morpho-physiological, Genomic, and Transcriptional Diversities in Response to Potassium Deficiency in Rapeseed (Brassica napus L.) Genotypes.

Variations in the resistance to potassium (K) deficiency among rapeseed genotypes emphasize complicated regulatory mechanisms. In this study, a low-K-sensitivity accession (L49) responded to K deficiency with smaller biomasses, severe leaf chlorosis, weaker photosynthesis ability, and deformed stomata morphology compared to a low-K resistant accession (H280). H280 accumulated more K+ than L49 under low K. Whole-genome resequencing (WGS) revealed a total of 5,538,622 single nucleotide polymorphisms (SNPs) and 859,184 insertions/deletions (InDels) between H280 and L49. RNA-seq identified more differentially expressed K+ transporter genes with higher expression in H280 than in L49 under K deficiency. Based on the K+ profiles, differential expression profiling, weighted gene coexpression network analysis, and WGS data between H280 and L49, BnaC4.AKT1 was proposed to be mainly responsible for root K absorption-mediated low K resistance. BnaC4.AKT1 was expressed preferentially in the roots and localized on the plasma membrane. An SNP and an InDel found in the promoter region of BnaC4.AKT1 were proposed to be responsible for its differential expression between rapeseed genotypes. This study identified a gene resource for improving low-K resistance. It also facilitates an integrated knowledge of the differential physiological and transcriptional responses to K deficiency in rapeseed genotypes.