Search

Abstract Background Chinese cancer survivors are not doing well in returning to work. Peer support, as an external coping resource to help cancer survivors return to work, brings together members of the lay community with similar stressors or problems for mutual support. Peer volunteers have not received systematic training, so inappropriate language in the support process can often cause secondary damage to both the peer and the cancer survivor. High-quality narrative support can help both parties gain positive meaning in communication. Therefore, we draw on narrative-related theoretical techniques to construct a model of peer narrative support to facilitate cancer survivors’ return to work. Methods This study is a participatory action research, including three phases: (i) Construction: Construct a peer narrative support model through literature review, theoretical research, and expert meetings. A peer narrative competence training program and a peer narrative support implementation program are constructed on this basis. (ii) Intervention: Firstly, two rounds of training actions will be carried out for 8 weeks. Second, after the peers have passed the training assessment, cancer survivors will be recruited to carry out two rounds of peer narrative support for six months. The model framework will be revised in conjunction with observation and reflection during the action. (iii) Evaluation: A combination of quantitative and qualitative methods will be used to assess the feasibility and scientific validity of the peer narrative support model and to evaluate the effectiveness of the intervention. The research methods used include theoretical research, literature review, expert meeting method, participatory observation method, interview method, and questionnaire survey method. Discussion China currently has cancer rehabilitation associations in most provinces, cities, and counties, and peer volunteers in these organisations use their personal experience to help other cancer patients. Currently, the content of their help is mostly limited to disease recovery and financial condolences, and there is a lack of scientific training for peer volunteers. This study aims to help patients cope with their suffering and eventually return to work by narrating the stories of role models. The narrative support covers three aspects: focusing on recovery, rebuilding effectiveness, and adjusting planning. In addition, this study relies on the methodology of action research to develop a peer narrative support model, training program, and implementation plan, which are more applicable to the national context of peer support for cancer patients in China. This will provide scientific guidance for the Chinese Cancer Rehabilitation Association to develop peer narrative support and guide cancer survivors back to work. Trial registration This study has been registered at the Chinese Clinical Trial Registry (Registration number ChiCTR2300068403) on Feb 17, 2023. (Retrospectively registered) https://www.chictr.org.cn/bin/project/edit?pid=183766 .

Abstract Background Human platelet lysate (hPL) has emerged as a promising serum substitute to enhance the self-renewal and multipotency of human mesenchymal stem cells (MSCs). Despite its potential, the specific biological mechanisms by which hPL influences MSC phenotypes remain inadequately understood. Methods We investigated the biological signaling activated by hPL in two common types of human MSCs: bone marrow-derived MSCs (BMSCs) and adipose-derived MSCs (ASCs). Cell adhesion and cell-matrix interaction were assessed through immunofluorescence staining and western blotting. The impact of hPL on lipid droplet formation in MSCs was thoroughly examined using oil red O/BODIPY staining, semi-quantitative analysis, and qRT-PCR. RNA sequencing and intracellular inhibition assays were also performed to elucidate the mechanisms by which hPL modulates MSC behavior. Results MSCs cultured in hPL medium demonstrated a reduction in cell size, spreading area, and vinculin puncta, while enhancing cell proliferation and lipid droplet accumulation compared to those cultured in control media. Notably, the lipid droplets in hPL-treated MSCs were significantly smaller than those in adipocyte-like cells differentiated from MSCs, highlighting hPL’s distinctive role in lipid production. Gene and protein expression profiles of hPL-treated MSCs differed from those in adipocyte-like cells. An angiogenic factor array revealed that hPL-MSCs had a distinct angiogenic factor profile compared to FBS-MSCs, with VEGF expression closely linked to HIF-1α expression. RNA-seq data identified approximately 1,900 differentially expressed genes (DEGs) between hPL-MSCs and FBS-MSCs, with enrichment in focal adhesion, ECM-receptor interaction, and PI3K-Akt/MAPK signaling pathways. Inhibition of MAPK phosphorylation significantly hampered lipid formation in hPL-MSCs, underscoring the pivotal role of MAPK signaling in hPL-driven adipogenesis. Conclusion This study reveals the biological mechanisms by which hPL infleunces MSC behavior and differentiation, offering new insights into its potential application in regenerative medicine and tissue engineering.

With the extensive development of coal resources in Shaanxi and Mongolia, rock burst phenomenon has gradually become an important problem affecting the safety production of coal mines. Aiming at the problem of uniform pressure relief of hard thick roof of rock burst coal seam, taking 23301 working face of a mine as the engineering background, ABAQUS numerical simulation software is used to simulate the hydraulic fracturing process of directional long drilling. The numerical simulation results show that the fractures mainly expand in the direction of perforation, and there is a dense fracture network around the fractured layer, and a single main fracture tends to form with the increase of the expansion radius, which proves that the fracturing operation can effectively achieve the purpose of roof pressure relief. The target strata were determined according to the theory of key strata and a high-low layout scheme was designed for the roof. The fracturing effect was discussed by focusing on the results of holes 2-1. The application results show that the fractures are mainly horizontal and the fracture network is complex. During fracturing, the injection pressure curve fluctuates zigzag in the fracture expansion zone and the expansion is fully and continuously. Fracturing operation significantly reduces the roadway deformation during mining, realizes the safe and efficient mining of the working face.

Abstract Background Observational studies have shown a link between autoimmune diseases and schizophrenia, with conflicting conclusions. Due to the existence of confounding factors, the causal link between autoimmune diseases and schizophrenia is still unknown. Method We conducted a comprehensive Mendelian randomization (MR) analysis of schizophrenia and ten common autoimmune diseases in individuals of European descent using genome-wide association studies (GWASs). To evaluate the relationships between autoimmune diseases and schizophrenia, inverse variance weighted, MR-RAPS, Bayesian weighted MR, constrained maximum likelihood, debiased IVW, MR-Egger, and weighted median were utilized. Several sensitivity analyses were performed to ensure the reliability of the study's results. Results Our findings reveal that genetically predicted ankylosing spondylitis is related to an increased risk of schizophrenia, whereas celiac disease, type 1 diabetes, and systemic lupus erythematosus are associated with a lower risk of schizophrenia. In the reverse MR analysis, our study indicated that genetically predicted schizophrenia is linked to higher risks of ankylosing spondylitis, Crohn's disease, ulcerative colitis, inflammatory bowel disease, and psoriasis. Neither multiple sclerosis nor rheumatoid arthritis have been linked to schizophrenia, and vice versa. Conclusion Despite contradicting some other observational reports, this study showed support for a causal link between autoimmune diseases and schizophrenia. To gain a better understanding of the mechanisms underlying the development of immune-mediated schizophrenia, additional research is required to identify potential mechanisms identified in observational studies.

Abstract In preclinical studies, p53 loss of function impacts chemotherapy response, but this has not been consistently validated clinically. We trained a TP53-loss phenocopy gene expression signature from pan-cancer clinical samples in the TCGA. In vitro, the TP53-loss phenocopy signature predicted chemotherapy response across cancer types. In a clinical dataset of 3003 breast cancer samples treated with neoadjuvant chemotherapy, the TP53-loss phenocopy samples were 56% more likely to have a pathologic complete response (pCR), with a significant association between TP53-loss phenocopy and pCR in both ER positive and ER negative tumors. In an independent clinical validation in the I-SPY2 trial (N = 987), we confirmed the association with neoadjuvant chemotherapy pCR and found higher rates of chemoimmunotherapy response in TP53-loss phenocopy tumors compared to non-TP53-loss phenocopy tumors (64% vs. 28%). The TP53-loss phenocopy signature predicts chemotherapy response across cancer types in vitro, and in a proof-of-concept clinical validation is associated with neoadjuvant chemotherapy response across multiple clinical breast cancer cohorts.

Abstract There are increasing concerns regarding the rapid expansion of polystyrene nanoplastics (PS-NPs), which could impact human health. Previous studies have shown that nanoplastics can be transferred from mothers to offspring through the placenta and breast milk, resulting in cognitive deficits in offspring. However, the neurotoxic effects of maternal exposure on offspring and its mechanisms remain unclear. In this study, PS-NPs (50 nm) were gavaged to female rats throughout gestation and lactation to establish an offspring exposure model to study the neurotoxicity and behavioral changes caused by PS-NPs on offspring. Neonatal rat hippocampal neuronal cells were used to investigate the pathways through which NPs induce neurodevelopmental toxicity in offspring rats, using iron inhibitors, autophagy inhibitors, reactive oxygen species (ROS) scroungers, P53 inhibitors, and NCOA4 inhibitors. We found that low PS-NPs dosages can cause ferroptosis in the hippocampus of the offspring, resulting in a decline in the cognitive, learning, and memory abilities of the offspring. PS-NPs induced NOCA4-mediated ferritinophagy and promoted ferroptosis by inciting ROS production to activate P53-mediated ferritinophagy. Furthermore, the levels of the antioxidant factors glutathione peroxidase 4 (GPX4) and glutathione (GSH), responsible for ferroptosis, were reduced. In summary, this study revealed that consumption of PS-NPs during gestation and lactation can cause ferroptosis and damage the hippocampus of offspring. Our results can serve as a basis for further research into the neurodevelopmental effects of nanoplastics in offspring. Graphical Abstract

ObjectiveThe Charlson Comorbidity Index (CCI) is a widely utilized assessment tool for evaluating the mortality rate among patients with chronic diseases and tumors. Currently, there is a dearth of research investigating the correlation between CCI and survival rates in advanced pancreatic cancer patients received immunotherapy. Therefore, this study aims to elucidate the association between CCI and survival rates in real-world settings for pancreatic cancer patients received immunotherapy.MethodsA total of 104 patients with advanced pancreatic cancer who received immunotherapy at the General Hospital of the People’s Liberation Army between September 2015 and September 2020 were included in this study. The patients were categorized into two groups based on their Charlson Comorbidity Index (CCI) scores: low CCI group (CCI

Aging is a complex biological process characterized by increased inflammation and susceptibility to various age-related diseases, including cognitive decline, osteoporosis, and type 2 diabetes. Exercise has been shown to modulate mitochondrial function, immune responses, and inflammatory pathways, thereby attenuating aging through the regulation of exerkines secreted by diverse tissues and organs. These bioactive molecules, which include hepatokines, myokines, adipokines, osteokines, and neurokines, act both locally and systemically to exert protective effects against the detrimental aspects of aging. This review provides a comprehensive summary of different forms of exercise for older adults and the multifaceted role of exercise in anti-aging, focusing on the biological functions and sources of these exerkines. We further explore how exerkines combat aging-related diseases, such as type 2 diabetes and osteoporosis. By stimulating the secretion of these exerkines, exercise supports healthy longevity by promoting tissue homeostasis and metabolic balance. Additionally, the integration of exercise-induced exerkines into therapeutic strategies represents a promising approach to mitigating age-related pathologies at the molecular level. As our understanding deepens, it may pave the way for personalized interventions leveraging physical activity to enhance healthspan and improve quality of life.

BackgroundWith the increasing utilization of anticoagulants, the selection of appropriate anticoagulants has emerged as a significant quandary. The objective of this study was to evaluate recent trend in the utilization and expenditure of anticoagulants within a specific region, aiming to provide valuable insights into the optimal choice of anticoagulants across other healthcare facilities.MethodsThe utilization of anticoagulants was retrospectively analyzed. The data on anticoagulant utilizations in tertiary-care hospitals within a district were collected from January 2019 to December 2023. The expenditure, defined daily doses (DDDs), and defined daily cost (DDC) were calculated. The trends in the utilization and expenditure of anticoagulants were examined using linear regression analysis.ResultsFrom 2019 to 2023, the DDDs of rivaroxaban demonstrated a significant annual increase in most hospitals (p < 0.05). Only a few hospitals exhibited a gradual rise in the consumption of low molecular weight heparin (LMWH) over the same period (p < 0.05). The trend of heparin sodium and warfarin varied across different hospitals. The implementation of the centralized procurement policy, however, resulted in a decline in the consumption of rivaroxaban and LMWH in 2021 and 2022 respectively. The DDC value of rivaroxaban experienced a substantial decrease over the past five years (p = 0.020), declining from 55.20 Chinese Yuan (CNY) in 2019 to 4.28 CNY in 2023. Conversely, there was a slight increase noted in the DDC of heparin sodium during this time frame (p = 0.042).ConclusionOver the past five years (2019-2023), there has been an increase in the utilization of rivaroxaban and LMWH. However, their expenditure has decreased. In addition, the utilization and expenditure of warfarin and heparin sodium remained relatively stable. The application prospects of rivaroxaban and LMWH are promising.

On some islands, the main source of residential water is groundwater, whose quality is seriously threatened by continuous industrial construction in island areas. However, there are few studies on the multivariate and spatiotemporal evaluation of the risk of island industrial construction to human health by threatening groundwater quality. Using an industrial park in Hainan as the study area, a model incorporating remote sensing cloud computing, the DRCSTLV model, the human health risk assessment (HHRA) model, and MODFLOW + MT3DMS + RT3D was established to provide a comprehensive assessment of health risks in the area from 2015 to 2022. The DRCSTLV model, which includes seven indicators along with associated potential health risks, is based on groundwater flow fields and pollutant transport models. The results of the comprehensive groundwater health risk assessment from 2015 to 2022 revealed that the annual maximum normalized health risk of groundwater in the study area show an overall fluctuating upward trend. The highest health risk values were stabilized by 2020, and the evaluation results for 2021 and 2022 increased slightly. However, the health risk in the center of the park reached Level 1 and above, and the risk area of Level 2 and above covered an area of up to 94,613 m2, accounting for 0.0039 of the entire study area. Finally, Monte Carlo simulations were used to conduct uncertainty and sensitivity analyses to reflect the objective reality of groundwater health risks under the combined influence of various uncertainty factors. The analysis revealed that the contributions of indicators D and L to the uncertainty were the highest. In addition, the diffusion of chemical oxygen demand in the vicinity of pollution sources has a significant impact on uncertainty. These findings provide valuable guidance for the prevention and control of groundwater pollution in island regions.

IntroductionSalvia miltiorrhiza radix et rhizoma (Danshen) is a crucial medicinal material for treating cardiovascular and cerebrovascular diseases. However, the presence of adulterants and intraspecific variability poses challenges to its clinical safety.MethodsThis study collected samples of S. miltiorrhiza from various regions and commonly encountered adulterants. The composition differences of S. miltiorrhiza radix and its adulterants were analyzed by fingerprint and broad-target metabolomics. Chloroplast genome was used to distinguish intra-genus species and DNA barcoding was used to identify germplasm sources.ResultsThe fingerprinting analysis proved that there is no chemical composition consistency between S. miltiorrhiza radix and its adulterants. Broad-targeted metabolomics can distinguish S. miltiorrhiza radix from Salvia yunnanensis radix, Dipsacus asperoides radix, and Arctium lappa radix. Additionally, comparative chloroplast genome analysis indicated that atpF and rps4-trnT-UGU were the potential DNA barcodes for S. miltiorrhiza. 259 samples from 13 provinces and 21 origins were amplified and sequenced, resulting in the identification of 62 haplotypes. The unique haplotypes found in Shanxi Luoyang, Shandong Qingdao and other places can be used as molecular geographic markers for the identification of the germplasm source of S. miltiorrhiza.DiscussionThis study systematically differentiates S. miltiorrhiza from its adulterants and highlights the potential of unique haplotypes as markers for sourcing. The findings provide strong scientific evidence for the clinical safety of S. miltiorrhiza, emphasizing the importance of proper cultivation, selection, and breeding of varieties.

IntroductionThis study aims to utilize proteomics, bioinformatics, and machine learning algorithms to identify diagnostic biomarkers in the serum of patients with acute and chronic brucellosisMethodsProteomic analysis was conducted on serum samples from patients with acute and chronic brucellosis, as well as from healthy controls. Differential expression analysis was performed to identify proteins with altered expression, while Weighted Gene Co-expression Network Analysis (WGCNA) was applied to detect co-expression modules associated with clinical features of brucellosis. Machine learning algorithms were subsequently used to identify the optimal combination of diagnostic biomarkers. Finally, ELISA was employed to validate the identified proteins.ResultsA total of 1,494 differentially expressed proteins were identified, revealing two co-expression modules significantly associated with the clinical characteristics of brucellosis. The Gaussian Mixture Model (GMM) algorithm identified six proteins that were concurrently present in both the differentially expressed and co-expression modules, demonstrating promising diagnostic potential. After ELISA validation, five proteins were ultimately selected.DiscussionThese five proteins are implicated in the innate immune processes of brucellosis, potentially associated with its pathogenic mechanisms and chronicity. Furthermore, we highlighted their potential as diagnostic biomarkers for brucellosis. This study further enhances our understanding of brucellosis at the protein level, paving the way for future research endeavors.

BackgroundPoor nutritional status may affect outcomes after coronary revascularization, but the association between nutritional status and outcomes in patients undergoing coronary revascularization has not been fully evaluated. This study was based on the MIMIC-IV database to analyze the impact of baseline nutritional status on poor outcomes in patients with coronary revascularization.MethodsPatients with coronary revascularization were screened from the MIMIC-IV database. A geriatric nutritional risk index (GNRI) was calculated and used to divide patients into 4 groups: no malnutrition (Q4: ≥96.79), mild malnutrition (Q3: 90.85–96.78), moderate malnutrition (Q2: 86.37–90.84), and severe malnutrition (Q1: 86.37). The primary outcome measure was 28-day mortality, and the secondary outcome measures were AKI and length of hospital stay. Cox proportional hazards model, Kaplan-Meier survival analysis, restricted cubic spline (RCS), and multiple linear regression model were used for statistical analysis, respectively, to ensure the robustness of study results.ResultsA total of 1,168 patients with coronary revascularization were included. The GNRI demonstrated a significant association with 28-day mortality in patients undergoing coronary revascularization. As a continuous variable, the GNRI exhibited a notable inverse correlation with mortality across unadjusted, partially adjusted, and fully adjusted Cox regression models [hazard ratios (HRs): 0.93, 0.94, 0.96, respectively; all P

Researchers have been widely attracted by the lining block falling accident of Fukuoka tunnel in Japan, with the main reason that the cold joints have cause the lining blocks falling. This article constructs a numerical calculation model of the Fukuoka tunnel lining, which is based on cohesive fatigue damage units. It analyzes the damage and deformation of lining blocks with cold joints under aerodynamic fatigue loads. The study also explores the extents of aerodynamic load amplitude, pouring intervals, and block positioning on the damage to cold joint units. The study shows that this method is suitable for analyzing the damage process of lining blocks with cold joints under aerodynamic fatigue loads. The discrepancy between the predicted detachment time (40 years) and the actual time (25 years) is attributed to unclear design parameters, the exclusion of train vibration loads, and the deterioration of concrete performance. The timing of cohesive unit damage is accelerated with increasing aerodynamic load amplitude and pouring intervals, while it is delayed when the block position is lower. The greater the normal force on the lining block with cold joints, the more likely the cold joint interface elements are to be damaged.

Abstract Background The purpose of this in vitro study was to compare and evaluate the stress distribution of maxillary first premolar residual crowns restored with post-core crowns, endocrowns and inlay crowns after deep margin elevation, to explore the fitting restoration for residual crowns using finite element analysis. Methods A healthy complete right maxillary first premolar from a male adult was scanned by cone beam computed tomography (CBCT). The finite element model of the tooth was established by reverse engineering software such as Mimics, Geomagic and Hypermesh. On this basis, the residual crown model after deep margin elevation was made, and the experimental group models were divided into three groups, those restored with post core crowns, endocrowns and inlay crowns. Vertical and oblique static loads were applied to the experimental models to simulate the force on the tooth during mastication (the loading position was located in the central fossa of the occipital surface, and the load was 100 N) using Abaqus software. Results The peak value and distribution of von Mises stress in each part of the experimental model were observed. After deep margin elevation, the peak dentin von Mises stresses were lower than the tensile strength of normal dentin in the post-core crown, endocrown, and inlay crown groups; the lowest stress results were found in the post-core crown group for the dentin, restoration, enamel, and deep margin elevation (DME) layers under vertical and oblique loading. In terms of stress distribution clouds, the peak stresses in the dentin tissue were located in the apical 1/3 of the root after postcore crown restorations for both loads, while stress concentrations were evident in the cervical and root areas after endocrown and inlay crown restorations; regardless of the load and restoration method, the corresponding stress concentration areas appeared at the junction of the DME and dentin tissue at the loading site of the restorations; Conclusions Post-core crowns, endocrowns and inlay crowns can be used to restore residual crowns after deep margin elevation, and post-core crowns can better protect the residual tooth tissue.

Abstract The trail making test (TMT) is a commonly used tool for evaluating executive functions, and the activation of cerebral oxygenation in the prefrontal cortex (PFC) during the test can reflect the participation of executive function. This study aimed to compare the differences in cerebral oxygenation in the PFC between the computer- and paper-based versions of the TMT and provide a theoretical basis for the optimization and clinical application of the computer-based version. A total of 32 healthy adult participants completed the computer- and paper-based TMT Types A and B. Cerebral oxygenation changes in the PFC were monitored during the experiment using near-infrared spectroscopy. Moreover, average changes in oxyhemoglobin (Δoxy-Hb) levels at the baseline and during activation periods in different types of testing were compared and analyzed. The number of correct connections in the computer-based version Type B was less than that in the paper-based version Type B (p

Abstract Background The interrelation between metabolic syndrome (MetS) and Parkinson’s disease (PD) likely arises from shared pathological mechanisms. This study thus aims to examine the impact of MetS and its components on PD. Methods This study utilized data extracted from the National Health and Nutrition Examination Survey database spanning 1999 to 2020. The random forest algorithm was applied to fill in the missing data. Propensity score optimal full matching was conducted. The data were adjusted by total weights derived from both sampling and matching weights. The weighted data were utilized to create multifactor logistic regression models. Odds ratios (ORs) and average marginal effects, along with their corresponding 95% confidence intervals (CIs), were calculated. Results MetS did not significantly affect the risk of PD (OR: 1.01; 95% CI: 0.77, 1.34; P = 0.92). Hypertension elevated the risk of PD (OR: 1.33; 95% CI: 1.01, 1.76; P = 0.045), accompanied by a 0.26% increased probability of PD occurrence (95% CI: 0.01%, 0.52%; P = 0.04). Diabetes mellitus (DM) had a 1.38 times greater likelihood of developing PD (OR:1.38; 95% CI: 1.004, 1.89; P = 0.046), corresponding to a 0.32% increased probability of PD occurrence (95% CI: -0.03%, 0.67%; P = 0.07). Nevertheless, no correlation was observed between hyperlipidemia, waist circumference and PD. Conclusion MetS does not affect PD; however, hypertension and DM significantly increase the risk of PD.

Engaging in exercise in an ozone (O3)-polluted environment can lead to lung damage, respiratory inflammation, and deterioration in performance, however, the effects on the heart are undefined. Herein, we report that rats performing moderate-intensity exercise under O3-polluted air evoked pathological myocardial hypertrophy (MH). O3 exposure increased serum levels of MH-promoting factors (angiotensin II [AngII], endothelin-1 [ET-1], and cyclophilin A [CyPA]), and decreased expression of MH-inhibiting factors (adiponectin [ADPN], follistatin-like protein 1 [FSTL1], and apelin). O3 exposure also increased the expression levels of cardiac hypertrophy markers (ANP, BNP, and β-MHC) in the heart, elicited myocardial hypertrophy and cardiac inflammation. Mechanistically, we identified lncRNA EYA4-au1 overexpression in the above myocardial tissues with pathological hypertrophy. In an AngII-elicited in vitro model, EYA4-au1 was shown to mediate cardiomyocyte hypertrophy. AngII induces nuclear translocation of SP1, leading to high expression of EYA4-au1; And inhibits the expression of ELAVL1, resulting in nuclear retention of EYA4-au1. Nuclear EYA4-au1 recruits Med11 to EYA4 promoter for transcriptional activation, subsequently unleashing the EYA4/p27kip1/CK2α/HDAC2 cascade that signals cardiomyocyte hypertrophy. In summary, O3 exposure is an important factor in pathological MH, mediated by EYA4-au1 that motivates the MH-driving EYA4 pathway. Our findings define the effects of exercise on the heart in an O3-polluted environment and offer a novel mechanistic route for the onset of MH.

To synthesize superheavy element 119 is becoming a highly concerned issue as several experimental projects in major laboratories are being pursued. This work studied the survival probabilities of compound superheavy nuclei after multiple neutron emissions based on microscopic energy dependent fission barriers, demonstrating a significant role of triaxial deformation in decreasing the first fission barriers in the heaviest region. Together with the fusion cross sections by the dinuclear system model, the optimal energy and the residual cross section of 243Am(48Ca, 3n)288Mc are reproduced. Finally the cross sections and optimal beam energies of 54Cr+243Am and 50Ti+249Bk reactions are estimated, providing clues for the synthesis of new elements.

Background: Exposed, infected and necrotic tendons often occur in the middle and late stages of diabetic foot ulcers (DFUs). The exposed tendon is both a potential source and route of infection, which prolongs the treatment period and affects recovery, leading to amputation and even death. Therefore, management of the exposed tendon in patients with DFU is the key to treatment. This study aimed to evaluate the clinical efficacy of Shengji ointment combined with bromelain in the treatment of DFU with tendon exposure and to provide clinical treatment options and evidence-based medicine. Methods: This study was a multicenter, nonblinded, randomized, positive controlled clinical trial involving 180 patients with DFU with tendon exposure at four tertiary-grade A-class hospitals. The included patients were randomly assigned 1:1 to an observation group (n = 90) that received Shengji ointment combined with bromelain and a control group (n = 90) that received hydrocolloid dressing, with dressing changes once daily for 4 weeks. Patients in both groups continued with conventional treatments, such as blood glucose and blood pressure medication, lipid regulation, and antiplatelets. The primary outcome measure was wound coverage with granulation tissue. The secondary outcome measures included the wound healing rate, time to granulation, Maryland foot score, time to debridement of necrotic tendon tissue, and granulation tissue score. We performed measurements before enrollment and after the end of treatment for comparison. Results: There was no significant difference in the baseline data between the two groups before treatment (P > 0.05). After treatment, the primary outcome indicators of the two groups were compared, and the wound granulation tissue coverage rate of the treatment group was greater than that of the control group (P = 0.003). For the secondary outcome outcomes, the wound healing rate, time to granulation, Maryland foot function score, time to debridement of necrotic tendon tissue, and granulation tissue score in the treatment group were significantly better than those in the control group (P

Parkinson’s disease (PD) is a neurodegenerative disease characterized by the gradual loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc), abnormal accumulation of α-synuclein (α-syn), and activation of microglia leading to neuroinflammation. Disturbances in circadian rhythm play a significant role in PD, with most non-motor symptoms associated with disruptions in circadian rhythm. These disturbances can be observed years before motor symptoms appear and are marked by the emergence of non-motor symptoms related to PD, such as rapid eye movement sleep behavior disorder (RBD), restless leg syndrome (RLS), excessive daytime sleepiness (EDS), depression and anxiety, changes in blood pressure, gastrointestinal dysfunction, and urinary problems. Circadian rhythm disruption precedes the onset of motor symptoms and contributes to the progression of PD. In brief, this article outlines the role of circadian rhythm disruption in triggering PD at cellular and molecular levels, as well as its clinical manifestations. It also explores how circadian rhythm research can contribute to preventing the onset and progression of PD from current and future perspectives.

ObjectiveTo study and predict the risk of ovarian metastasis (OM) in patients with cervical adenocarcinoma (ADC).MethodsPatients with ADC who received surgical treatment from January 2015 to December 2022 in the Obstetrics and Gynecology Hospital of Fudan University were included in the study. Patients were further divided into OP (ovaries were preserved in surgery) and BSO (bilateral salpingo-oophorectomy) groups. For the patients who accepted BSO, 60% of the patients were randomly grouped into a training cohort, and predictive prognostic models were constructed with 10-fold cross-validation through random forest, LASSO, stepwise, and optimum subset analysis. The model with the highest area under receiver operator curve (AUC) was screened out in the testing cohort. The nomogram and its calibration curve presented the possibility of OM in future patients. The prognoses between the different populations were compared using Kaplan–Meier analysis. All data processing was carried out in R 4.2.0 software.ResultsA total of 934 patients were enrolled in our cohort; 266 patients had their ovaries preserved and 668 patients had BSO according to the previous criteria reported The clinical safety with these criteria was secured, while the 5-year overall survival had no significant difference between the BSO and OP groups (p = 0.069), which suggested that the current criteria could be extended and are more precise. Four predictive models for ovarian metastasis by machine learning were constructed in our study, and the random forest model that obtained the highest AUC in both training and testing sets (0.971 for training and 0.962 for testing set) was taken as the best model. The optimal cut-off point of the ROC curve (specificity 99.5% and 90% sensitivity) was utilized to stratify the patients into high- and low-risk OM. Further comparing the survival curves of the high and low-OM risk groups, it was found that both DFS and OS were significantly prolonged in the low-risk group (p < 0.01). On the basis of this random forest model, a nomogram was used to calculate the OM risk, and the results were validated with calibration. The predictive model was further applied to the whole cohort (934 patients), and we identified the OM low-risk population (n = 822) and the patients with high risk who should be recommended for BSO (n = 112). No significant difference was found in the 5-year survival between the low-risk group with our model and the patients who already had ovaries preserved according to the previous criteria (n = 266).ConclusionThe predictive model constructed in our study could identify the low-risk population of OM in patients with ADC, which remarkably extended the number with the previous criteria, for whom we could potentially preserve ovaries to help improve their life quality.

Pullulan is a kind of natural polymer, which is widely used in medicine and food because of its solubility, plasticity, edible, non-toxicity and good biocompatibility. It is of great significance to improve the yield of pullulan by genetic modification of microorganisms. It was previously reported that Aureobasidium melanogenum TN3-1 isolated from honey-comb could produce high-yield of pullulan, but the molecular mechanisms of its production of pullulan had not been completely solved. In this study, the reported strains of Aureobasidium spp. were further compared and analyzed at genome level. It was found that genome duplication and genome genetic variations might be the crucial factors for the high yield of pullulan and stress resistance. This particular phenotype may be the result of adaptive evolution, which can adapt to its environment through genetic variation and adaptive selection. In addition, the TN3-1 strain has a large genome, and the special regulatory sequences of its specific genes and promoters may ensure a unique characteristics. This study is a supplement of the previous studies, and provides basic data for the research of microbial genome modification in food and healthcare applications.

Abstract Glioma, particularly glioblastomas (GBM), is incurable brain tumor. The most targeted receptor tyrosine kinase (RTKs) drugs did not bring benefit to GBM patients. The mechanism of glioma growth continues to be explored to find more effective treatment. Here, we reported that Ser/Thr protein kinase YANK2 (yet another kinase 2) is upregulated in glioma tissues and promotes the growth and proliferation of glioma in vitro and in vivo. Further, we confirmed that oncogene Fyn directly activated YANK2 through phosphorylation its Y110, and Fyn-mediated YANK2 phosphorylation at Y110 site promotes glioma growth by increasing its stability. Finally, YANK2 was proved to be a novel upstream kinase of p70S6K and promotes glioma growth by directly phosphorylating p70S6K at T389. Taken together, we found a new mTOR-independent p70S6K activation pathway, Fyn-YANK2-p70S6K, which promotes glioma growth, and YANK2 is a potential oncogene and serves as a novel therapeutic target for glioma.

Abstract Background Adolescents with depression who engage in non-suicidal self harming behaviors are more likely to adopt negative coping strategies when faced with negative events. Therefore, these patients should be introduced to positive coping strategies. Evidences have showed that mindfulness-based interventions can positively impact the psychology of patients with mental disorders. This study was to explore the impact of a combination of mindfulness therapy and mentalization-based family therapy (MBFT) on suicidal ideation in adolescents with depressive disorder. Methods Eighty adolescent patients with depression and suicidal ideation admitted to our hospital from September 2021 to February 2022 were selected as subjects. They were divided into a control group and a study group using the random number table method, with each group comprising 40 subjects. The control group received MBFT, whereas the study group received both mindfulness therapy and MBFT. The psychological status and suicidal ideations of the two groups were compared before and after the intervention. Results The psychological health scores of both groups of patients were lower after the intervention, with the scores of the study group being lower than those of the control group (P

Abstract Objectives To explore the effects of a ‘Rebuilding Myself’ intervention on enhancing the adaptability of cancer patients to return to work. Methods A single-center, single-blind, randomized controlled trial design was used. Eligible patients who were receiving routine hospital treatment were recruited from the university-affiliated hospital in our city. Patients in the control group only received usual care, while patients in the intervention group received additional ‘Rebuilding Myself’ intervention. Adaptability to return to work, self-efficacy of returning to work, mental resilience, quality of life and work ability were measured at baseline, the 6th and 12th of the intervention. The general estimation equations were used to compare the overall changes of each outcome index between the two groups at different time points. Considering that there may be patient shedding and rejection, Per-Protocol and Intention-to-Treat analysis were used to analyze the data in this study. Results There were statistically significant differences between the two groups of patients in the cancer patients’ adaptability to return to work, self-efficacy to return to work, mental resilience, work abilities, the physical, emotional, cognitive function, fatigue, insomnia and overall health status dimensions of quality of life (P 0.05). The group effect, time effect, and interaction effect of patients’ return to work adaptability and return to work self-efficacy were statistically significant in both groups (P

Abstract Background The triglyceride glucose (TyG) index is a novel and reliable alternative marker for insulin resistance. Previous studies have shown that TyG index is closely associated with cardiovascular outcomes in cardiovascular diseases and coronary revascularization. However, the relationship between TyG index and renal outcomes of coronary revascularization is unclear. The purpose of this study was to investigate the correlation between TyG index and the risk of acute kidney injury (AKI) in patients with coronary revascularization. Methods A retrospective cohort study was conducted to select eligible patients with coronary revascularization admitted to ICU in the medical information mart for intensive care IV (MIMIC-IV). According to the TyG index quartile, these patients were divided into four groups (Q1-Q4). The primary endpoint was the incidence of AKI, and secondary endpoints included 28-day mortality and the rate of renal replacement therapy (RRT) use in the AKI population. Multivariate Cox regression analysis and restricted cubic splines (RCS) were used to analyze TyG index association with AKI risk. Kaplan-Meier survival analysis was performed to assess the incidence of endpoints in the four groups. Results In this study, 790 patients who underwent coronary revascularization surgery were included, and the incidence of AKI was 30.13%. Kaplan-Meier analysis showed that patients with a high TyG index had a significantly increased incidence of AKI (Log-rank P = 0.0045). Multivariate Cox regression analysis showed that whether TyG index was a continuous variable (HR 1.42, 95% CI 1.06–1.92, P = 0.018) or a categorical variable (Q4: HR 1.89, 95% CI 1.12–3.17, P = 0.017), and there was an independent association between TyG index and AKI in patients with coronary revascularization. The RCS curve showed a linear relationship between higher TyG index and AKI in this particular population (P = 0.078). In addition, Kaplan-Meier analysis showed a significantly increased risk of RRT application in a subset of AKI patients based on quartiles of TyG index (P = 0.029). Conclusion TyG index was significantly associated with increased risk of AKI and adverse renal outcomes in patients with coronary revascularization. This finding suggests that the TyG index may be useful in identifying people at high risk for AKI and poor renal outcomes in patients with coronary revascularization.

Abstract Background Atrial fibrillation (AF) is the most common cardiac arrhythmia worldwide. Catheter ablation has become a crucial treatment for AF. However, there is a possibility of atrial fibrillation recurrence after catheter ablation. Our study sought to elucidate the role of lncRNA‒mRNA regulatory networks in late AF recurrence after catheter ablation. Methods We conducted RNA sequencing to profile the transcriptomes of 5 samples from the presence of recurrence after AF ablation (P-RAF) and 5 samples from the absence of recurrence after AF ablation (A-RAF). Differentially expressed genes (DEGs) and long noncoding RNAs (DE-lncRNAs) were analyzed using the DESeq2 R package. The functional correlations of the DEGs were assessed through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. A protein‒protein interaction (PPI) network was constructed using STRING and Cytoscape. We also established a lncRNA‒mRNA regulatory network between DE-lncRNAs and DEGs using BEDTools v2.1.2 software and the Pearson correlation coefficient method. To validate the high-throughput sequencing results of the hub genes, we conducted quantitative real-time polymerase chain reaction (qRT‒PCR) experiments. Results A total of 28,528 mRNAs and 42,333 lncRNAs were detected. A total of 96 DEGs and 203 DE-lncRNAs were identified between the two groups. GO analysis revealed that the DEGs were enriched in the biological processes (BPs) of “regulation of immune response” and “regulation of immune system process”, the cellular components (CCs) of “extracellular matrix” and “cell‒cell junction”, and the molecular functions (MFs) of “signaling adaptor activity” and “protein–macromolecule adaptor activity”. According to the KEGG analysis, the DEGs were associated with the “PI3K–Akt signaling pathway” and “MAPK signaling pathway.” Nine hub genes (MMP9, IGF2, FGFR1, HSPG2, GZMB, PEG10, GNLY, COL6A1, and KCNE3) were identified through the PPI network. lncRNA-TMEM51-AS1-201 was identified as a core regulator in the lncRNA‒mRNA regulatory network, suggesting its potential impact on the recurrence of AF after catheter ablation through the regulation of COL6A1, FGFR1, HSPG2, and IGF2. Conclusions The recurrence of atrial fibrillation after catheter ablation may be associated with immune responses and fibrosis, with the extracellular matrix playing a crucial role. TMEM51-AS1-201 has been identified as a potential key target for AF recurrence after catheter ablation.

Abstract Background Antral follicles consist of an oocyte cumulus complex surrounding by somatic cells, including mural granulosa cells as the inner layer and theca cells as the outsider layer. The communications between oocytes and granulosa cells have been extensively explored in in vitro studies, however, the role of oocyte-derived factor GDF9 on in vivo antral follicle development remains elusive due to lack of an appropriate animal model. Clinically, the phenotype of GDF9 variants needs to be determined. Methods Whole-exome sequencing (WES) was performed on two unrelated infertile women characterized by an early rise of estradiol level and defect in follicle enlargement. Besides, WES data on 1,039 women undergoing ART treatment were collected. A Gdf9 Q308X/S415T mouse model was generated based on the variant found in one of the patients. Results Two probands with bi-allelic GDF9 variants (GDF9 His209GlnfsTer6/S428T , GDF9 Q321X/S428T ) and eight GDF9 S428T heterozygotes with normal ovarian response were identified. In vitro experiments confirmed that these variants caused reduction of GDF9 secretion, and/or alleviation in BMP15 binding. Gdf9 Q308X/S415T mouse model was constructed, which recapitulated the phenotypes in probands with abnormal estrogen secretion and defected follicle enlargement. Further experiments in mouse model showed an earlier expression of STAR in small antral follicles and decreased proliferative capacity in large antral follicles. In addition, RNA sequencing of granulosa cells revealed the transcriptomic profiles related to defective follicle enlargement in the Gdf9 Q308X/S415T group. One of the downregulated genes, P4HA2 (a collagen related gene), was found to be stimulated by GDF9 protein, which partly explained the phenotype of defective follicle enlargement. Conclusions GDF9 bi-allelic variants contributed to the defect in antral follicle development. Oocyte itself participated in the regulation of follicle development through GDF9 paracrine effect, highlighting the essential role of oocyte-derived factors on ovarian response.

Abstract Background Helicobacter pylori (H. pylori), according to a number of recent observational studies, is connected to atherosclerosis (AS). However, the link between H. pylori and AS is debatable. Methods In order to calculate the causal relationship between H. pylori and AS, we employed a two-sample Mendelian randomization (MR) analysis. The data for H. pylori were obtained from the IEU GWAS database ( https://gwas.mrcieu.ac.uk/datasets/ ) and the data for AS were obtained from the Finngen GWAS database ( https://r5.finngen.fi/ ). We selected single nucleotide polymorphisms with a threshold of 5 × 10–6 from earlier genome-wide association studies. MR was performed mainly using the inverse variance weighted (IVW) method. To ensure the reliability of the findings, We performed a leave-one-out sensitivity analysis to test for sensitivity. F-value was used to test weak instrument. Results A positive causal relationship between H. pylori OMP antibody levels and peripheral atherosclerosis was shown by our two-sample MR analysis (odds ratio (OR) = 1.33, 95% confidence interval (CI) = 1.14–1.54, P = 0.26E-03) using IVW. Additionally, there was a causative link between coronary atherosclerosis and H. pylori VacA antibody levels (IVW OR = 1.06, 95% CI = 1.01–1.10, P = 0.016). All the F-values were above 10. Conclusions This MR study discovered a causal link between H. pylori and AS. Different antibodies have different effects, so future researches are needed to figure out the exact mechanisms behind this link.

Abstract In type-II Weyl semimetals (WSMs), the tilting of the Weyl cones leads to the coexistence of electron and hole pockets that touch at the Weyl nodes. These electrons and holes experience the Berry curvature generated by the Weyl nodes, leading to an anomalous Hall effect that is highly sensitive to the Fermi level position. Here we have identified field-induced ferromagnetic MnBi2-xSbxTe4 as an ideal type-II WSM with a single pair of Weyl nodes. By employing a combination of quantum oscillations and high-field Hall measurements, we have resolved the evolution of Fermi-surface sections as the Fermi level is tuned across the charge neutrality point, precisely matching the band structure of an ideal type-II WSM. Furthermore, the anomalous Hall conductivity exhibits a heartbeat-like behavior as the Fermi level is tuned across the Weyl nodes, a feature of type-II WSMs that was long predicted by theory. Our work uncovers a large free carrier contribution to the anomalous Hall effect resulting from the unique interplay between the Fermi surface and diverging Berry curvature in magnetic type-II WSMs.

Abstract Histopathologic diagnosis and classification of cancer plays a critical role in guiding treatment. Advances in next-generation sequencing have ushered in new complementary molecular frameworks. However, existing approaches do not independently assess both site-of-origin (e.g. prostate) and lineage (e.g. adenocarcinoma) and have minimal validation in metastatic disease, where classification is more difficult. Utilizing gradient-boosted machine learning, we developed ATLAS, a pair of separate AI Tumor Lineage and Site-of-origin models from RNA expression data on 8249 tumor samples. We assessed performance independently in 10,376 total tumor samples, including 1490 metastatic samples, achieving an accuracy of 91.4% for cancer site-of-origin and 97.1% for cancer lineage. High confidence predictions (encompassing the majority of cases) were accurate 98–99% of the time in both localized and remarkably even in metastatic samples. We also identified emergent properties of our lineage scores for tumor types on which the model was never trained (zero-shot learning). Adenocarcinoma/sarcoma lineage scores differentiated epithelioid from biphasic/sarcomatoid mesothelioma. Also, predicted lineage de-differentiation identified neuroendocrine/small cell tumors and was associated with poor outcomes across tumor types. Our platform-independent single-sample approach can be easily translated to existing RNA-seq platforms. ATLAS can complement and guide traditional histopathologic assessment in challenging situations and tumors of unknown primary.

Abstract Non-volatile phase-change memory devices utilize local heating to toggle between crystalline and amorphous states with distinct electrical properties. Expanding on this kind of switching to two topologically distinct phases requires controlled non-volatile switching between two crystalline phases with distinct symmetries. Here, we report the observation of reversible and non-volatile switching between two stable and closely related crystal structures, with remarkably distinct electronic structures, in the near-room-temperature van der Waals ferromagnet Fe5−δ GeTe2. We show that the switching is enabled by the ordering and disordering of Fe site vacancies that results in distinct crystalline symmetries of the two phases, which can be controlled by a thermal annealing and quenching method. The two phases are distinguished by the presence of topological nodal lines due to the preserved global inversion symmetry in the site-disordered phase, flat bands resulting from quantum destructive interference on a bipartite lattice, and broken inversion symmetry in the site-ordered phase.

Background Gross motor coordination (GMC) plays a crucial factor in children’s motor development and daily activities. It encompasses various sub-capacities, such as spatial orientation, rhythm, and motor reaction, collectively referred to as basic coordination capacities (BCC). However, children who are overweight and obese (OW/OB) often display poorer GMC. This study aims to examine the impact of gender and weight status (BMI categories) on children’s GMC and BCC. It also seeks to investigate the impact of BCC and BMI on GMC. Method The study involved 266 participants, 135 in the NW group (boys: n = 75; girls: n = 60) and 131 in the OW/OB group (boys: n = 68; girls: n = 63). An NW status is defined by a BMI z-score between ≥−2SD to ≤1SD, while an OW/OB status corresponds to a BMI z-score > 1SD. Physical activity was assessed using the Physical Activity Questionnaire for Children, developed by the University of Saskatchewan, Canada. We used six field tests to evaluate BCC, including single leg standing test (static balance), YBT (dynamic balance), rhythmic sprint test (rhythm), reaction time test (motor reaction), target standing broad test (kinesthetic differentiation), and numbered medicine ball running test (spatial orientation). GMC was evaluated with Kiphard-Schilling’s Body Coordination Test (KTK). Result The motor quotient (MQ) was primarily affected by weight status (F = 516.599, p < 0.001; gender: F = 6.694, p = 0.01), with no significant interaction effect (F = 0.062, p = 0.803). In BCC, gender had a significant main effect on rhythm capacity (F = 29.611, p < 0.001) and static balance (F = 11.257, p = 0.001) but did not significant influence other sub-capacities (p > 0.05). Weight status impacted dynamic balance (F = 11.164, p = 0.001). The interaction of gender and weight status significantly impacted motor reaction (F = 1.471, p = 0.024) and kinesthetic differentiation (F = 5.454, p = 0.02), but did not affect other sub-capacities (p > 0.05). The physical activity was not significant affected by gender (F = 0.099, p = 0.753), weight status (F = 0.171, p = 0.679) and the interactions of two variables (F = 0.06, p = 0.806). In the regression analysis, except motor reaction (p > 0.05), other BCC sub-capacities influenced GMC to varying extents (β = −0.103–0.189, p < 0.05). Nonetheless, only two types of balance significantly mediated the relationship between BMI and GMC (BMI→MQ: β = −0.543, p < 0.001; BMI→YBT: β = −0.315, p < 0.001; BMI→SLS: β = −0.282, p < 0.001; SLS→MQ: β = 0.189, p < 0.001; YBT→MQ: β = 0.182, p < 0.001). Conclusion Compared to gender, the main effect of weight status on most GMC and BCC’s sub-capacities was more pronounced. OW/OB children exhibited poorer GMC, which is related to their reduced static and dynamic balance due to excess weight. Kinesthetic differentiation, spatial orientation, and rhythm capacity are not significantly associated with BMI, but these sub-capacities positively influence gross motor coordination (GMC), except for hand-eye motor reaction.

Small nucleolar RNAs (snoRNAs) have robust potential functions and therapeutic value in breast cancer. Herein, we investigated the role SNORA5A in breast cancer. Samples from The Cancer Genome Atlas (TCGA) were reviewed. The transcription matrix and clinical information were analyzed using R software and validated in clinical tissue samples. SNORA5A was significantly down-regulated in breast cancer, and high expression of SNORA5A correlated with a favorable prognosis. High expression of SNORA5A induced a high concentration of tumor-associated macrophages M1 and a low concentration of tumor-associated macrophages M2. Moreover, SNORA5A were clustered in terms related to cancer and immune functions. Possible downstream molecules of SNORA5A were identified, among which TRAF3IP3 was positively correlated with M1 and negatively correlated with M2. The function of TRAF3IP3 in tumor inhibition and its relationship with macrophages in clinical tissue samples were in accordance with bioinformatics analysis results. SNORA5A could regulate macrophage phenotypes through TRAF3IP3 and serves as a potential prognostic marker for breast cancer patients.

ObjectiveTubo-ovarian carcinosarcomas are rare, extremely aggressive malignant tumors that contain both carcinomatous and sarcomatous components. Due to the disease’s rarity, developing an effective treatment strategy for ovarian carcinosarcomas has been challenging. A study was conducted to investigate the clinicopathologic and molecular features of this rare disease.MethodsWe enrolled all patients diagnosed with tubo-ovarian carcinosarcomas from January 2007 to December 2022. The clinical and pathological data were gathered from medical records. Kaplan–Meier curves were plotted to calculate OS and PFS. The Log-rank test and Cox regression model were utilized to explore the relationship between clinicopathological parameters and survival. Patients with cancer tissues available had sequencing with a 242-gene panel done to investigate the mutational landscape and signature of the disease.ResultsIn total, 65% of the patients were diagnosed with advanced-stage cancer. The median PFS and OS of this cohort were 27 and 40 months, respectively, and there was no significant difference in survival between the homologous and heterologous components of sarcoma. Unexpectedly, staging did not have effects on prognosis. All patients had surgical attempts, and suboptimal debulking status was correlated with poorer PFS and OS. MSI was identified in 0% with low Tumor mutation burden (TMB) indicating a poor response to immunotherapy. Low HER2 expression is controversial, according to previous reports, and gives us limited choices with this rare and aggressive disease. We surprisingly found the homologous recombination deficiency (HRD)-positive status was identified in 64% of OCS, which is significantly higher than UCS and other types of epithelial ovarian cancer. The fact that all patients in our cohort who received olaparib as maintenance therapy had survived over 30 months and two had no evidence of recurrence at the latest follow-up might further validate the role of poly (ADP-ribose) polymerase inhibitors (PARPi) in the management of OCS.ConclusionOCS patients seemed to respond to carboplatin/paclitaxel with optimal PFS and OS. Cytoreduction with no residuals proved to be the sole independent prognostic factor. WES should be done to assess the prognosis and assist with the targeted therapy, especially the HRD test, which might help select potential patients who benefit from PARPi.

Parkinson’s disease (PD) is a prevalent neurodegenerative disorder that affects the central nervous system (CNS). Neuroinflammation is a crucial factor in the pathological advancement of PD. PD is characterized by the presence of activated microglia and increased levels of proinflammatory factors, which play a crucial role in its pathology. During the immune response of PD, microglia regulation is significantly influenced by microRNA (miRNA). The excessive activation of microglia, persistent neuroinflammation, and abnormal polarization of macrophages in the brain can be attributed to the dysregulation of certain miRNAs. Additionally, there are miRNAs that possess the ability to inhibit neuroinflammation. miRNAs, which are small non-coding epigenetic regulators, have the ability to modulate microglial activity in both normal and abnormal conditions. They also have a significant impact on promoting communication between neurons and microglia.

Micro(nano)plastic, as a new type of environmental pollutant, have become a potential threat to the life and health of various stages of biology. However, it is not yet clear whether they will affect brain development in the fetal stage. Therefore, this study aims to explore the potential effects of nanoplastics on the development of fetal rat brains. To assess the allocation of NPs (25 nm and 50 nm) in various regions of the fetal brain, pregnant rats were exposed to concentrations (50, 10, 2.5, and 0.5 mg/kg) of PS-NPs. Our results provided evidence of the transplacental transfer of PS-NPs to the fetal brain, with a prominent presence observed in several cerebral regions, notably the cerebellum, hippocampus, striatum, and prefrontal cortex. This distribution bias might be linked to the developmental sequence of each brain region. Additionally, we explored the influence of prenatal exposure on the myelin development of the cerebellum, given its the highest PS-NP accumulation in offspring. Compared with control rats, PS-NPs exposure caused a significant reduction in myelin basic protein (MBP) and myelin oligodendrocyte glycoprotein (MOG) expression, a decrease in myelin thickness, an increase in cell apoptosis, and a decline in the oligodendrocyte population. These effects gave rise to motor deficits. In conclusion, our results identified the specific distribution of NPs in the fetal brain following prenatal exposure and revealed that prenatal exposure to PS-NPs can suppress myelin formation in the cerebellum of the fetus.

We investigated the potential of ferric iron-modified biochar to lessen autotrophic nitrification and lower nitrous oxide (N2O) emissions in paddy soils. A 15N tracing incubation was conducted to investigate the changes in soil gross nitrogen (N) transformations under various biochar amendments (control, unmodified biochar, and Fe-modified biochar). Acetylene and 1-octyne were used to assess the relative contributions of ammonia-oxidizing bacteria (AOB) and ammonia-oxidizing archaea (AOA) to N2O emission from paddy soil. The Fe-modified biochar increased the rate of NH4+ immobilization by 26 % and 383 % compared to the control and unmodified biochar treatments, respectively. The gross rate of autotrophic nitrification was reduced to 5.43 μg N g−1 d−1 in the Fe-modified biochar treatment, compared to 6.74 μg N g−1 d−1 in the control treatment and 9.38 μg N g−1 d−1 in the unmodified biochar treatment. Soil pH had varying effects on N2O emissions involving AOB and AOA. The N2O yields of AOA were more sensitive to Fe-modified biochar applications. AOB, specifically the Nitrosopira-AOB genus, dominated N2O production in all treatments. Overall, this study suggests that Fe-modified biochar holds greater potential than unmodified biochar in reducing N2O emissions from paddy soils by stimulating NH4+ adsorption, restraining autotrophic nitrification rates, and AOB-dominant N2O production pathways.

Objectives: We aimed to investigate the continuous changes in respiratory virus epidemics in hospitalized children with lower respiratory tract infections (LRTIs) persisting from January 2019 to December 2022 in Wuhan, China. Methods: We retrospectively enrolled children with LRTIs admitted to the Wuhan Children's Hospital. Specimens were nasopharyngeal aspirates which had been collected and detected the following microorganisms with direct immunofluorescence: influenza virus types A and B, respiratory syncytial virus, parainfluenza virus types 1-3, and adenovirus. We also analyzed demographic data and laboratory test results. Results: A total of 22,660 patients were enrolled. The total virus detection rate in 2019, 2021, and 2022 significantly declined gradually (36.96% vs 29.47% vs 22.62%, P value < 0.001). All the detected viruses did not follow previously observed seasonal patterns during the COVID-19 pandemic. Children hospitalized for LRTIs were older during the COVID-19 pandemic in contrast to the pre-period, particularly notable in cases attributed to respiratory syncytial virus and parainfluenza virus type 3 infections. Conclusions: This work adds to our knowledge of the epidemiology characteristics of respiratory viruses spanning the COVID-19 pandemic among children with LRTIs. The circulation of respiratory viruses changed consistently, and active LRTI surveillance in children remains critical for defining the healthcare burden of respiratory viruses.

Abstract Background There is mounting proof that rheumatoid arthritis (RA) and cognitive decline are related. These studies, however, have not all been uniform, and others have not discovered such a correlation. It is essential to investigate the link between RA and cognitive decline. Method We conducted a Mendelian randomization analysis utilizing three different publicly accessible RA GWAS summary datasets and a variety of meticulously verified instrumental variables. We mostly used inverse variance weighting (IVW), as well as MR-Egger, weighted median, MR-PRESSO, and several sensitivity analyses, to figure out the link between RA and cognitive impairment (CI). Results Our MR study identified the causality between RA and declining cognitive performance (β = − 0.010, 95% CI of − 0.017 to − 0.003, P = 4.33E−03) and cognitive function (β = − 0.029, 95% CI of − 0.053 to − 0.005, P = 1.93E−02). The consistent direction of the connection is revealed by sensitivity analysis utilizing the weighted median and the MR-Egger method. Furthermore, we reproduced our findings across two additional RA datasets and found identical outcomes, strengthening the validity of our findings. Conclusion This study offers proof of causality between RA and an increased risk of CI. Our findings highlight the importance of examining RA patients for cognitive ability, which may open up fresh ideas for the prevention of CI.

Abstract Background and objective Numerous previous studies have assessed the prognostic role of 18F-fluorodeoxyglucose positron-emission tomography (18F FDG PET) in patients with biliary tract cancer (BTC), but those results were inconsistent. The present study aims to determine the predictive value of 18F FDG PET in BTC patients via a meta-analysis. Methods The underlying studies related to 18F FDG PET and BTC patients` outcomes were searched and identified in the online databases. The interested parameters include total lesion glycolysis (TLG), metabolic tumor volume (MTV), primary tumor and metastatic lymph node (LN) maximum standardized uptake value (SUVmax), as well as change of SUVmax (ΔSUVmax) during treatment. Overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS) were considered as the primary endpoints. Hazard ratio (HR) and corresponding 95% confidence intervals (CIs) were defined as the effective measure and calculated by a pooled analysis. Publication bias was assessed by funnel plot, Bagg’s and Egger’s tests. Results Totally, 23 studies involving 1478 patients were included in the present meta-analysis. After a pooled analysis, it revealed that a high SUVmax was significantly associated with a poor OS (HR:2.07, 95%CI: 1.74–2.46, P = 0.000) and DFS (HR: 2.28, 95%CI: 1.53–3.41, P = 0.000). In addition, an increased TLG level contributed to a shorter OS (HR:1.91, 95%CI: 1.26–2.90, P = 0.002) and DFS (HR: 4.34, 95%CI: 1.42–13.27, P = 0.01). Moreover, we confirmed that an elevated MTV was significantly associated with increased mortality (HR:2.04, 95%CI:1.26–3.31, P = 0.004) and disease relapse (HR: 3.88, 95%CI:1.25–12.09, P = 0.019) risks. Besides, the present study uncovered that increased ΔSUVmax could predict poor OS (HR:1.26, 95%CI:1.06–1.50, P = 0.008) instead of PFS (HR: 1.96, 95%CI: 0.82–4.72, P = 0.280). Lastly, we found that LN SUVmax did not link to OS (HR: 1.49, 95%CI: 0.83–2.68, P = 0.178). No obvious publication bias was detected in the present study. Conclusion 18F FDG PET parameters, including SUVmax, TLG, MTV, and ΔSUVmax, could be applied as convenient and reliable factors for predicting BTC patients` outcomes.

Background Mycoplasma pneumoniae (M. pneumoniae) is an important pathogen of community-acquired pneumonia in children. The factors contributing to the severity of illness caused by M. pneumoniae infection are still under investigation. We aimed to evaluate the sensitivity of common M. pneumoniae detection methods, as well as to analyze the clinical manifestations, genotypes, macrolide resistance, respiratory microenvironment, and their relationship with the severity of illness in children with M. pneumoniae pneumonia in Wuhan. Results Among 1,259 clinical samples, 461 samples were positive for M. pneumoniae via quantitative polymerase chain reaction (qPCR). Furthermore, we found that while serological testing is not highly sensitive in detecting M. pneumoniae infection, but it may serve as an indicator for predicting severe cases. We successfully identified the adhesin P1 (P1) genotypes of 127 samples based on metagenomic and Sanger sequencing, with P1-type 1 (113/127, 88.98%) being the dominant genotype. No significant difference in pathogenicity was observed among different genotypes. The macrolide resistance rate of M. pneumoniae isolates was 96% (48/50) and all mutations were A2063G in domain V of 23S rRNA gene. There was no significant difference between the upper respiratory microbiome of patients with mild and severe symptoms. Conclusions During the period of this study, the main circulating M. pneumoniae was P1-type 1, with a resistance rate of 96%. Key findings include the efficacy of qPCR in detecting M. pneumoniae, the potential of IgM titers exceeding 1:160 as indicators for illness severity, and the lack of a direct correlation between disease severity and genotypic characteristics or respiratory microenvironment. This study is the first to characterize the epidemic and genomic features of M. pneumoniae in Wuhan after the COVID-19 outbreak in 2020, which provides a scientific data basis for monitoring and infection prevention and control of M. pneumoniae in the post-pandemic era.

Fluctuations in the surface water are indicators of climatic and biological environmental variations. The water index method is the predominant approach for water extraction owing to its simplicity of operation and high efficiency. Recognizing the limitations of individual water indices in extracting water over dense time-sequences, this study introduces a combined water index (CWI) frequency method to improve the water extraction results. The research findings indicate the following: 1) CWI demonstrates superior extraction accuracy for various types of water when compared with other water indices, underscoring its higher precision and broader applicability. 2) By integrating CWI with the water frequency method, we propose an effective approach for dynamically monitoring water. This method accurately reflects changes in water under different conditions within dense time-sequence images. 3) Our results highlight the method's ability to precisely monitor dynamic water changes, efficiently extract various water types from Sentinel-2 data, and its potential for large-scale surface water mapping applications.

Abstract To explore whether ferroptosis is involved in focal segmental glomerulosclerosis (FSGS) and its mechanism. The FSGS rat model was constructed by single nephrectomy combined with fractional tail vein injection of doxorubicin. 24-hour urine protein, serum biochemistry, HE, PAS and Masson pathological staining were measured to assess renal injury. Glomerular and morphological changes of ferroptosis were observed by transmission electron microscopy. Iron content in renal tissue was assessed by Prussian blue staining and iron detection. GSH/GSSG kit was used to detect the content and proportion of reduced/oxidized glutathione. Lipid peroxidation related proteins including MDA expression was assessed by colorimetry. The iron metabolism biomarkers such as hepcidin, ferroportin and TFR, ferroptosis biomarkers such as GPX4, ACSL4, and ferritinophagy biomarkers such as LC3II/LC3I, NCOA4, and FTH1 were detected by Western blot. Significant urinary protein, hyperlipidemia, azotemia, increased serum creatinine and hypoproteinemia were observed in FSGS rats. Histology and electron microscopy showed segmental sclerosis of glomeruli, compensatory enlargement of some glomeruli, occlusion of capillary lumen, balloon adhesion, increased mesangial matrix, atrophy of some tubules, and renal interstitial fibrosis in renal tissue of FSGS rats. The morphology of glomerular foot processes disappeared; the foot processes were extensively fused and some foot processes detached. Mitochondria became smaller, membrane density increased, and mitochondrial cristae decreased or disappeared. In addition, iron deposition was observed in renal tissue of FSGS rats. Compared with the control group, the levels of GSH, GSH/GSSG, GPX4, and ferroportin were reduced and the expression of GSSG, MDA, ACSL4, hepcidin, and TFR was increased in the renal tissue of FSGS rats; meanwhile, the expression of LC3II/LC3I and NCOA4 was increased and the expression of FTH1 was decreased. Ferroptosis is involved in the pathological progression of FSGS, which is probably associated with activation of ferritinophagy. This represents a potential therapeutic target for FSGS.

Monolayer nanosheets of zirconium phosphate in aqueous suspension exhibit short-range repulsion and long-range attraction, producing, at overall volume fractions larger than about half a percent, phase separation into higher-concentration liquid crystal and lower-concentration isotropic regions. At high concentrations, this phase separation takes the form of an emulsion of condensed, liquid-crystalline droplets, which anneal to form lens-shaped tactoids. These tactoids provide an opportunity to study the liquid crystal ordering of inorganic nanosheets in the limit of large shape anisotropy (diameter/thickness~400) and high packing fraction (volume fraction ≳ 70%). The internal liquid crystal structure of the tactoids remains nematic even under conditions that would usually favor ordering into lamellar smectics. Local lamellar ordering is suggested by short-range, smectic-like layer correlations, but a full transition into a smectic phase appears to be inhibited by the nanosheet edges, which act as a perturbative population of dislocation loops in the system of layers. Under conditions of thermal equilibrium, the nanoplates organize positionally to enable bend deformation of the director, a hallmark of the nematic phase and its principal distinction from the smectic, where bend must be expelled.

In the field of cement, if the formation cannot be given sufficient pressure to maintain stability during construction, pressure control failure may occur, leading to the leakage of liquids and gasses from the formation to the wellbore. In addition, irregular wellbore diameter and casing eccentricity are important factors that are easily overlooked and affect the prediction of ECD (Equivalent Circulation Density) calculation. This results in major accidents and ecological disasters, further impacting the global environment. This study focuses on a well in the eastern oilfields of China, and based on a rheological experiment of high temperature and high pressure, an irregular eccentric wellbore model is established according to the measured wellbore diameter and eccentricity data to calculate the ECD of the whole cementing process. Then, a data set is constructed and analyzed using the random forest method to quantitatively evaluate influencing factors such as displacement, rheology, density, and eccentricity on the bottomhole and wellbore ECD. Results find that the density of cement slurry and drilling fluid has the most significant impact on the maximum ECD, with the impact reaching 0.3142 and 0.2902, respectively, and the main factors that affect the minimum ECD are the density and rheological changes in the drilling fluid, reaching 0.7014 and 0.2846. These research findings will contribute to the precise control of wellbore pressure during cementing operations, further ensuring the safety of cementing operations, and laying a technical foundation for the automation and intelligentization of subsequent cementing operations.

The functional components known as milk oligosaccharides are crucial in the milk of diverse animals. Increasing evidence of immunomodulatory effects of milk oligosaccharides suggests that they may have some therapeutic potential in allergy. Here, we assess the effect of 3′-sialyllactose (3′-SL) on symptomatology and immune responses in a β-lactoglobulin (β-Lg)-sensitized mouse model of food allergy. Furthermore, 3′-SL mixed with 2′-fucosyllactose (2′-FL) at weight ratios of 1:6 and 1 000:1 to explore whether they had a synergies effect on alleviate sensitization. The results showed that 3′-SL and the mixture of 3′-SL and 2′-FL can regulate immune response and intestinal homeostasis. The intervention of 3′-SL and its mixture with 2′-FL can alleviate the symptoms of dermatitis, significantly reduce the serum specific-immunoglobulin (Ig) E (s-IgE) and specific-IgG1 (s-IgG1) levels (P < 0.05), reduce the accumulation of mast cells in the jejunum and maintain the diversity of the intestinal flora. 3′-SL could alleviate sensitization in a dose-dependent manner, and 3′-SL and 2′-FL have a synergies effect in reducing allergy. This study presented here opens the possibility that 3′-SL and the mixture of 3′-SL and 2′-FL in the form of nutritional ingredients could be used as adjuncts to existing treatment approaches to relieve food allergy in infants.