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Abstract Background Currently, most elderly chronic heart failure (CHF) patients go home for rehabilitation after certain treatment in hospitals. However, the results of their rehabilitation at home are not satisfactory. According to studies, dyadic treatments can increase the efficiency of home rehabilitation, enhance both partners' quality of life, lessen the caregiver's load of care, and alleviate the strain of medical resources. Thus, the aim of our research is to design a study protocol that included elderly CHF patients and their informal caregivers as an intervention unit and to explore the impact of the protocol on their health and physical outcomes. Methods This is a prospective randomized controlled trial conducted in a triple-A hospital. In total, 80 elderly CHF patients and informal caregivers (80 dyads) will be recruited with informed consent. Based on the randomized numbers, they are divided into a control group (40 dyads) and an intervention group (40 dyads), subjects in the control group will receive usual care, and subjects in the intervention group will receive a home-based disease management program based on the Theory of Dyadic Illness Management on the basis of the control group. The duration of the intervention is 3 months, and the follow-up is 6 months. Data is collected at enrolment, 3 months after the intervention, and 3 months after the end of the intervention. The primary outcome is patients’ quality of life and readmission. Secondary outcomes include patients’ self-management behaviors, anxiety, and depression and caregivers’ quality of life and care burden. Discussion This study focuses on whether this home-based disease management program can improve the quality of life of elderly patients with CHF, reduce the readmission rate, enhance their self-management capacity, reduce negative emotions, and reduce the burden of informal caregivers. It can provide a new perspective on home management and cardiac rehabilitation of heart failure disease in the elderly, as well as alleviate problems such as the burden of healthcare resources. Trial registration Chinese Clinical Trials Registry ChiCRT2300068026. Registered on 3 February 2023, manuscript Version: 1.0, https://www.chictr.org.cn/ .

Osteoarthritis (OA) is a highly incident total joint degenerative disease with cartilage degeneration as the primary pathogenesis. The cartilage matrix is mainly composed of collagen, a matrix protein with a hallmark triple-helix structure, which unfolds with collagen degradation on the cartilage surface. A collagen hybridizing peptide (CHP) is a synthetic peptide that binds the denatured collagen triple helix, conferring a potential disease-targeting possibility for early-stage OA. Here, we constructed an albumin nanoparticle (An) conjugated with CHP, loaded with a chondrogenesis-promoting small molecule drug, kartogenin (KGN). The CHP-KGN-An particle exhibited sustained release of KGN in vitro and prolonged in vivo retention selectively within the degenerated cartilage in the knee joints of model mice with early-stage OA. Compared to treatment with KGN alone, CHP-KGN-An robustly attenuated cartilage degradation, synovitis, osteophyte formation, and subchondral bone sclerosis in OA model mice and exhibited a more prominent effect on physical activity improvement and pain alleviation. Our study showcases that targeting the degenerated cartilage by collagen hybridization can remarkably promote the efficacy of small molecule drugs and may provide a novel delivery strategy for early-stage OA therapeutics.

Abstract Recent evidence has demonstrated that abnormal expression and regulation of circular RNA (circRNAs) are implicated in the development and progression of various tumors. The aim of this study was to investigate the effects of circ_SMA4 in Gastrointestinal Stromal Tumors (GISTs) malignant progression. Human circRNAs microarray analysis was conducted to identify differentially expressed (DE) circRNAs in GISTs. The effect of circ_SMA4 on cell proliferation, invasion, migration, and apoptosis was assessed in both in vitro and in vivo settings. Dual-luciferase reporter assay, RT-qPCR, Western-blot, and rescue assay were employed to confirm the interaction between circ_SMA4/miR-494-3p/ KIT axis. The results revealed that circ_SMA4 was significantly upregulated in GISTs, and exhibited high diagnostic efficiency with an AUC of 0.9824 (P

Abstract Oxidative stress and neuroinflammation contribute to schizophrenia (SCZ) pathology and may influence treatment efficacy. Matrix metalloproteinase 9 (MMP9) is a critical molecular node mediating the interaction between oxidative stress and inflammation, and so may influence treatment efficacy. Here we examined the associations of plasma MMP9 concentration with antipsychotic drug responses, clinical symptoms, and brain structure. A total of 129 healthy controls and 124 patients with SCZ were included in this study. Patients were monitored clinically during 8 weeks of antipsychotic treatment and classified as poor responders (n = 49) or good responders (n = 75). We then compared plasma MMP9 concentrations in healthy controls at baseline and both SCZ responder groups at baseline and after the 8-week antipsychotic treatment regimen. Cognitive function was also examined using the MATRICS Consensus Cognitive Battery. In addition, we extracted regional white matter density from magnetic resonance images of patients. Compared to healthy controls, plasma MMP9 levels were significantly elevated in poor responders at baseline and negatively correlated with both white matter density in the right superior temporal gyrus and the change in cognitive symptoms after treatment. Conversely, there was no significant difference in plasma MMP9 between good responders and healthy controls, and no associations of plasma MMP9 with cognitive symptoms or regional white matter density among good responders. Elevated plasma MMP9 is associated with poor antipsychotic drug efficacy and white matter deficits in SCZ patients, and so may be a useful biomarker to guide personalized treatment.

Abstract The Sox gene family, a collection of transcription factors widely distributed throughout the animal kingdom, plays a crucial role in numerous developmental processes. Echinoderms occupy a pivotal position in many research fields, such as neuroscience, sex determination and differentiation, and embryonic development. However, to date, no comprehensive study has been conducted to characterize and analyze Sox genes in echinoderms. In the present study, the evolution and expression of Sox family genes across 11 echinoderms were analyzed using bioinformatics methods. The results revealed a total of 70 Sox genes, with counts ranging from 5 to 8 across different echinoderms. Phylogenetic analysis revealed that the identified Sox genes could be categorized into seven distinct classes: the SoxB1 class, SoxB2 class, SoxC class, SoxD class, SoxE class, SoxF class and SoxH class. Notably, the SoxB1, SoxB2, and SoxF genes were ubiquitously present in all the echinoderms studied, which suggests that these genes may be conserved in echinoderms. The spatiotemporal expression patterns observed for Sox genes in the three echinoderms indicated that various Sox members perform distinct functional roles. Notably, SoxB1 is likely involved in echinoderm ovary development, while SoxH may play a crucial role in testis development in starfish and sea cucumber. In general, the present investigation provides a molecular foundation for exploring the Sox gene in echinoderms, providing a valuable resource for future phylogenetic and genomic studies.

Abstract Invasive candidiasis (IC) is a notable healthcare-associated fungal infection, characterized by high morbidity, mortality, and substantial treatment costs. Candida albicans emerges as a principal pathogen in this context. Recent academic advancements have shed light on the critical role of exosomes in key biological processes, such as immune responses and antigen presentation. This burgeoning body of research underscores the potential of exosomes in the realm of medical diagnostics and therapeutics, particularly in relation to fungal infections like IC. The exploration of exosomal functions in the pathophysiology of IC not only enhances our understanding of the disease but also opens new avenues for innovative therapeutic interventions. In this investigation, we focus on exosomes (Exos) secreted by macrophages, both uninfected and those infected with C. albicans. Our objective is to extract and analyze these exosomes, delving into the nuances of their protein compositions and subgroups. To achieve this, we employ an innovative technique known as Proximity Barcoding Assay (PBA). This methodology is pivotal in our quest to identify novel biological targets, which could significantly enhance the diagnostic and therapeutic approaches for C. albicans infection. The comparative analysis of exosomal contents from these two distinct cellular states promises to yield insightful data, potentially leading to breakthroughs in understanding and treating this invasive fungal infection. In our study, we analyzed differentially expressed proteins in exosomes from macrophages and C. albicans -infected macrophages, focusing on proteins such as ACE2, CD36, CAV1, LAMP2, CD27, and MPO. We also examined exosome subpopulations, finding a dominant expression of MPO in the most prevalent subgroup, and a distinct expression of CD36 in cluster14. These findings are crucial for understanding the host response to C. albicans and may inform targeted diagnostic and therapeutic approaches. Our study leads us to infer that MPO and CD36 proteins may play roles in the immune escape mechanisms of C. albicans. Additionally, the CD36 exosome subpopulations, identified through our analysis, could serve as potential biomarkers and therapeutic targets for C. albicans infection. This insight opens new avenues for understanding the infection's pathology and developing targeted treatments.

Abstract Background Dermatomyositis (DM) is an infrequent disease subgroup of idiopathic inflammatory myopathies characterized by distinct skin lesions. However, high heterogeneity makes clinical diagnosis and treatment of DM very challenging. Objectives Unsupervised classification in DM patients and analysis of key factors related to clinical outcomes. Methods This retrospective study was conducted between 2017 and 2022 at the Department of Rheumatology, Xiangya Hospital, Central South University. 162 DM patients were enrolled for unsupervised hierarchical cluster analysis. In addition, we divided the clinical outcomes of DM patients into four subgroups: withdrawal, stabilization, aggravation, and death, and compared the clinical profiles amongst the subgroups. Results Out of 162 DM patients, three clusters were defined. Cluster 1 (n = 40) was mainly grouped by patients with prominent muscular involvement and mild Interstitial Lung Disease (ILD). Cluster 2 (n = 72) grouped patients with skin rash, anti-Melanoma Differentiation Associated protein 5 positive (anti-MDA5+), and Rapid Progressive Interstitial Lung Disease (RP-ILD). Cluster 3 (n = 50) grouped patients with the mildest symptoms. The proportion of death increased across the three clusters (cluster 3 < cluster 1 < cluster 2). Study limitations The number of cases was limited for the subsequent construction and validation of predictive models. We did not review all skin symptoms or pathological changes in detail. Conclusions We reclassified DM into three clusters with different risks for poor outcome based on diverse clinical profiles. Clinical serological testing and cluster analysis are necessary to help clinicians evaluate patients during follow-up and conduct phenotype-based personalized care in DM.

Abstract Background Understanding the intricate influences of risk factors contributing to suicide among young individuals remains a challenge. The current study employed interpretable machine learning and network analysis to unravel critical suicide-associated factors in Chinese university students. Methods A total of 68,071 students were recruited between Sep 2016 and Sep 2020 in China. Students reported their lifetime experiences with suicidal thoughts and behaviors, categorized as suicide ideation (SI), suicide plan (SP), and suicide attempt (SA). We assessed 36 suicide-associated factors including psychopathology, family environment, life events, and stigma. Local interpretations were provided using Shapley additive explanation (SHAP) interaction values, while a mixed graphical model facilitated a global understanding of their interplay. Results Local explanations based on SHAP interaction values suggested that psychoticism and depression severity emerged as pivotal factors for SI, while paranoid ideation strongly correlated with SP and SA. In addition, childhood neglect significantly predicted SA. Regarding the mixed graphical model, a hierarchical structure emerged, suggesting that family factors preceded proximal psychopathological factors, with abuse and neglect retaining unique effects. Centrality indices derived from the network highlighted the importance of subjective socioeconomic status and education in connecting various risk factors. Conclusions The proximity of psychopathological factors to suicidality underscores their significance. The global structures of the network suggested that co-occurring factors influence suicidal behavior in a hierarchical manner. Therefore, prospective prevention strategies should take into account the hierarchical structure and unique trajectories of factors.

Abstract Introduction Dysnatremia is strongly associated with poor prognosis in acute kidney injury (AKI); however, the impact of sodium trajectories on the prognosis of patients with AKI has not yet been well elucidated. This study aimed to assess the association between sodium trajectories in patients with AKI and mortality at 30-day and 1-year follow-up. Methods This retrospective cohort study used data from Medical Information Mart for Intensive Care (MIMIC)-IV database, and patients diagnosed with AKI within 48 h after admission were enrolled. Group-based trajectory models (GBTM) were applied to map the developmental course of the serum sodium fluctuations. Kaplan–Meier survival curve was used to compare differences in mortality in AKI patients with distinct serum sodium trajectories. Hazard ratios (HRs) were calculated to determine the association between trajectories and prognosis using Cox proportional hazard models. Results A total of 9,314 AKI patients were enrolled. Three distinct sodium trajectories were identified including: (i) stable group (ST, in which the serum sodium levels remained relatively stable, n = 4,935; 53.0%), (ii) descending group (DS, in which the serum sodium levels declined, n = 2,994; 32.15%) and (iii) ascending group (AS, in which the serum sodium levels were elevated, n = 1,383; 14.85%). There was no significant difference in age and gender distribution among the groups. The 30-day mortality rates were 7.9% in ST, 9.5% in DS and 16.6% in AS (p

Background The process of aging often accompanies a decline in cognitive function, postural control, and gait stability, consequently increasing the susceptibility to falls among older individuals. In response to these challenges, motor-cognitive training has emerged as a potential intervention to mitigate age-related declines. Objective This study aims to assess the acute effects of two distinct motor-cognitive training modalities, treadmill dual-task training (TMDT) and interactive motor-cognitive training (IMCT), on cognitive function, postural control, walking ability, and dual-task performance in the elderly population. Method In this randomized crossover study, 35 healthy elderly individuals (aged 60–75) participated in three acute training sessions involving TMDT, IMCT, and a control reading condition. Assessments of executive function, postural control, gait performance, and cognitive accuracy were conducted both before and after each session. Results Both TMDT and IMCT improved executive functions. Notably, IMCT resulted in a significant enhancement in correct response rates and a reduction in reaction times in the Stroop task (p < 0.05) compared to TMDT and the control condition. IMCT also led to an increase in dual-task gait speed (p < 0.001) and showed a trend towards improved cognitive accuracy (p = 0.07). Conversely, TMDT increased postural sway with eyes open (p = 0.013), indicating a potential detriment to postural control. Conclusion The findings suggest that IMCT holds greater immediate efficacy in enhancing cognitive function and gait stability among older adults compared to TMDT, with a lesser adverse impact on postural control. This underscores the potential of IMCT as a preferred approach for mitigating fall risk and enhancing both cognitive and physical functions in the elderly population.

ObjectiveCognitive impairment represents a notable feature of depressive disorders. Comprehending its characteristics and influencing factors is vital for patient rehabilitation.MethodsThis study is based on the 2015 Shandong Province epidemiological survey of mental disorders, from which 871 individuals meeting DSM-IV criteria for depressive disorders were selected as the research group. Using 1:1:1 matching by sex, age, and residence, we randomly selected 825 individuals with no DSM-IV diagnosis but positive on GHQ-12 and additional risk assessments as the elevated risk control group, and 825 with negative screenings as the minimal risk control group. In 2020, a follow-up survey was conducted, resulting in a final analysis of 1,855 cases. The survey included demographic data, various clinical information, and a series of screening and questionnaire assessments.ResultsThe current depressive group scored lower on the MoCA than the non-depressive group (t=8.86, P

The arena of exosomal research presents substantial emerging prospects for clinical dermatology applications. This investigation conducts a thorough analysis of the contemporary global research landscape regarding exosomes and their implications for dermatological applications over the preceding decade. Employing bibliometric methodologies, this study meticulously dissects the knowledge framework and identifies dynamic trends within this specialized field. Contemporary scholarly literature spanning the last decade was sourced from the Web of Science Core Collection (WoSCC) database. Subsequent to retrieval, both quantitative and visual analyses of the pertinent publications were performed utilizing the analytical software tools VOSviewer and Citespace. A comprehensive retrieval yielded 545 scholarly articles dated from January 1, 2014, to December 31, 2023. Leading the research forefront are institutions such as Shanghai Jiao Tong University, The Fourth Military Medical University, and Sun Yat-sen University. The most prolific contributors on a national scale are China, the United States, and South Korea. Among the authors, Zhang Bin, Zhang Wei, and Zhang Yan emerge as the most published, with Zhang Bin also achieving the distinction of being the most cited. The International Journal of Molecular Sciences leads in article publications, whereas Stem Cell Research & Therapy holds the pinnacle in citation rankings. Theranostics boasts the highest impact factor among the periodicals. Current research hotspots in this area include Adipose mesenchymal stem cell-derived exosomes(ADSC-Exos), diabetic skin wounds, cutaneous angiogenesis, and the combination of biomaterials and exosomes. This manuscript constitutes the inaugural comprehensive bibliometric analysis that delineates the prevailing research trends and advancements in the clinical application of exosomes in dermatology. These analyses illuminate the contemporary research focal points and trajectories, providing invaluable insights that will inform further exploration within this domain.

Retinal ischemia is an ophthalmic emergency often caused by cardiovascular diseases, leading to irreversible vision loss and even blindness. Innovative retinal ischemia treatments are needed due to limited options. The pathological mechanisms involve retinal cell apoptosis and microglial activation. The pituitary adenylate cyclase-activating polypeptide (PACAP) is a well distributed neuropeptide found in both central nervous system and peripheral organs. Though it shows great anti-apoptosis and anti-microglia activation properties, it is rapidly cleared by intravitreal injection. Herein, we established a novel poly(ethylene glycol) (PEG) hydrogel system by cross-linking 4arm-PEG-NHS and 4arm-PEG-NH2 to load PACAP (PACAP@Gel-PEG), which exhibited great fluidity, injectability, structural recovery ability, moderate swelling ratio and drug release ability that were appropriate for drug delivery. Then the safety and effectiveness of the PACAP@Gel-PEG were evaluated in vitro in three retinal cell lines (ARPE-19, 661 W and rRMC) and in vivo using the unilateral common carotid artery occlusion (UCCAO) mice model. The CCK-8 test and live/dead staining demonstrated that PACAP@Gel-PEG exhibited excellent biocompatibility in three retinal cell lines. Furthermore, after PACAP@Gel-PEG treatment, a great anti-apoptotic effect was observed in cells treated by CoCl2. Application of PACAP@Gel-PEG greatly improved the therapeutic efficacy of PACAP in restoring retinal function, maintaining retinal integrity, and suppressing apoptosis and microglia activation in retinal tissues. Moreover, in mice, the biosafety of PACAP@Gel-PEG was confirmed by H&E staining of systemic organs. Taken together, our results demonstrated PACAP@Gel-PEG as a promising therapeutic option for retinal ischemia, providing new strategies for vision restoration.

IntroductionThis paper constructs a revenue model for an independent electrochemical energy storage (EES) power station with the aim of analyzing its full life-cycle economic benefits under the electricity spot market.MethodsThe model integrates the marginal degradation cost (MDC), energy arbitrage, ancillary services, and annual operation and maintenance (O&M) costs to calculate the net profits of the EES power station. Using an iterative optimization approach, we determine the optimal MDC and analyze the economic end of life (EOL) for different types of EES power stations.ResultsBy examining real-world examples from the California energy market, we find that the full life-cycle benefits of an EES power station peak when its MDC is optimal, at $45/MWh-throughput. Under these conditions, the economic and physical EOL of commercial/industrial EES power station is 9 years, while the economic EOL of residential-grade EES power station is 8 years, which is shorter than their physical EOL of 9 years.DiscussionThe study further indicates that the economic life of an EES power station is influenced by multiple factors, and operators need to determine the optimal economic EOL to maximize revenue based on battery degradation characteristics, market conditions and operational strategy.

PurposeAccurate preoperative identification of Human epidermal growth factor receptor 2 (HER2) low expression breast cancer (BC) is critical for clinical decision-making. Our aim was to use machine learning methods to develop and validate an ultrasound-based radiomics nomogram for predicting HER2-low expression in BC.MethodsIn this retrospective study, 222 patients (108 HER2-0 expression and 114 HER2-low expression) with BC were included. The enrolled patients were randomly divided into a training cohort and a test cohort with a ratio of 8:2. The tumor region of interest was manually delineated from ultrasound image, and radiomics features were subsequently extracted. The features underwent dimension reduction using the least absolute shrinkage and selection operator (LASSO) algorithm, and rad-score were calculated. Five machine learning algorithms were applied for training, and the algorithm demonstrating the best performance was selected to construct a radiomics (USR) model. Clinical risk factors were integrated with rad-score to construct the prediction model, and a nomogram was plotted. The performance of the nomogram was assessed using receiver operating characteristic curve and decision curve analysis.ResultsA total of 480 radiomics features were extracted, out of which 11 were screened out. The majority of the extracted features were wavelet features. Subsequently, the USR model was established, and rad-scores were computed. The nomogram, incorporating rad-score, tumor shape, border, and microcalcification, achieved the best performance in both the training cohort (AUC 0.89; 95%CI 0.836-0.936) and the test cohort (AUC 0.84; 95%CI 0.722-0.958), outperforming both the USR model and clinical model. The calibration curves showed satisfactory consistency, and DCA confirmed the clinical utility of the nomogram.ConclusionThe nomogram model based on ultrasound radiomics exhibited high prediction value for HER2-low BC.

BackgroundDespite its excellent therapeutic efficacy, albumin-bound paclitaxel often leads to peripheral neurotoxicity, significantly affecting patients’ quality of life. This study reported a case of non-small cell lung cancer (NSCLC) with peripheral neurotoxicity induced by albumin-bound paclitaxel.Case presentationA 70-year-old male was admitted to the Hubei Cancer Hospital complaining of left-side limb weakness and numbness for one month following the first cycle of albumin paclitaxel plus cisplatin plus tislelizumab regimen for the right-side NSCLC in December 2021. Chest CT displayed a soft tissue density mass in the apical segment of the right upper lung lobe (5.5×4.9 cm2). Immunohistochemistry results and CT-guided percutaneous lung biopsy confirmed NSCLC stage cT3NXMX. The pain and numbness in both feet were alleviated after the first cycle of this regimen of liposomal paclitaxel 240 mg plus cisplatin 90 mg plus tislelizumab 200 mg. After four treatment cycles, the tumor treatment was evaluated as partial response (PR), and the tumor lesion became 2.9×2.7 cm2.ConclusionThe regimen containing liposomal paclitaxel, cisplatin, and tislelizumab alleviated the symptoms of peripheral neurotoxicity induced by albumin-bound paclitaxel in an NSCLC case, which may be a potential therapeutic option.

Objective Adolescents face various health challenges due to academic pressures and sedentary lifestyles. Establishing healthy habits during this critical period is essential for long-term well-being. With the widespread use of fitness apps, understanding their impact on adolescent health behaviors and the underlying mechanisms is crucial. Guided by social support theory and social comparison theory, this study examined the influence of WeRun, a fitness app within WeChat, on adolescents’ adoption of healthy lifestyles. It investigated the correlation between WeRun usage and healthy behaviors, as well as the underlying mechanisms driving this relationship. Methods A cross-sectional survey was conducted across 31 provinces and metropolitans in China, utilizing a random cluster sampling approach targeting high school and freshman students aged 15–24 ( N = 1312). A parallel mediation model was employed to test the hypotheses. Results The analysis showed that WeRun use positively predicted both social support and social comparison. Meanwhile, both social support and social comparison were positively associated with healthy lifestyles. Additionally, WeRun use could not directly predict healthy lifestyles. However, WeRun use indirectly predicted healthy lifestyles via social support and social comparison. Conclusions The study's findings revealed the pivotal roles of social support and social comparison as mediating variables in the relationship between adolescents’ WeRun usage and adoption of healthy lifestyles. The results contributed to the current comprehension of the mechanisms linking app utilization to health-promoting behaviors. Furthermore, it provided valuable insights for promoting adolescent health and informed improved design strategies for fitness apps.

BackgroundNowadays, social media plays a crucial role in disseminating information about cancer prevention and treatment. A growing body of research has focused on assessing access and communication effects of cancer information on social media. However, there remains a limited understanding of the comprehensive presentation of cancer prevention and treatment methods across social media platforms. Furthermore, research comparing the differences between medical social media (MSM) and common social media (CSM) is also lacking. ObjectiveUsing big data analytics, this study aims to comprehensively map the characteristics of cancer treatment and prevention information on MSM and CSM. This approach promises to enhance cancer coverage and assist patients in making informed treatment decisions. MethodsWe collected all posts (N=60,843) from 4 medical WeChat official accounts (accounts with professional medical backgrounds, classified as MSM in this paper) and 5 health and lifestyle WeChat official accounts (accounts with nonprofessional medical backgrounds, classified as CSM in this paper). We applied latent Dirichlet allocation topic modeling to extract cancer-related posts (N=8427) and identified 6 cancer themes separately in CSM and MSM. After manually labeling posts according to our codebook, we used a neural-based method for automated labeling. Specifically, we framed our task as a multilabel task and utilized different pretrained models, such as Bidirectional Encoder Representations from Transformers (BERT) and Global Vectors for Word Representation (GloVe), to learn document-level semantic representations for labeling. ResultsWe analyzed a total of 4479 articles from MSM and 3948 articles from CSM related to cancer. Among these, 35.52% (2993/8427) contained prevention information and 44.43% (3744/8427) contained treatment information. Themes in CSM were predominantly related to lifestyle, whereas MSM focused more on medical aspects. The most frequently mentioned prevention measures were early screening and testing, healthy diet, and physical exercise. MSM mentioned vaccinations for cancer prevention more frequently compared with CSM. Both types of media provided limited coverage of radiation prevention (including sun protection) and breastfeeding. The most mentioned treatment measures were surgery, chemotherapy, and radiotherapy. Compared with MSM (1137/8427, 13.49%), CSM (2993/8427, 35.52%) focused more on prevention. ConclusionsThe information about cancer prevention and treatment on social media revealed a lack of balance. The focus was primarily limited to a few aspects, indicating a need for broader coverage of prevention measures and treatments in social media. Additionally, the study’s findings underscored the potential of applying machine learning to content analysis as a promising research approach for mapping key dimensions of cancer information on social media. These findings hold methodological and practical significance for future studies and health promotion.

Objectives: This research aims to establish a copper homeostasis-related gene signature for predicting the prognosis of epithelial ovarian cancer and to investigate its underlying mechanisms. Methods: We mainly constructed the copper homeostasis-related gene signature by LASSO regression analysis. Then multiple methods were used to evaluate the independent predictive ability of the model and explored the mechanisms. Results: The 15-copper homeostasis-related gene (15-CHRG) signature was successfully established. Utilizing an optimal cut-off value of 0.35, we divided the training dataset into high-risk and low-risk subgroups. Kaplan-Meier analysis revealed that survival times for the high-risk subgroup were significantly shorter than those in the low-risk group (P

With the widespread use of tetracycline antibiotics (TCs) and the application of manure fertilizer in farmland, TCs and their metabolites especially 4-epimers have been heavily detected in agricultural soil. However, existing studies have focused on the residual and environmental behavior of maternal TCs, and few studies have looked at the ecotoxicity of their 4-epimers in soil. In this study, the degradation and interconversion of tetracycline (TC), oxytetracycline (OTC) and their 4-epimers (4-epitetracycline, ETC; 4-epioxytetracycline, OTC) were revealed. Their effects on antibiotic resistance genes (ARGs), mobile genetic elements (MGEs) and bacterial community in soil were also investigated in comparison. The results showed that the 4-epimers could be substantially transformed to their parents and degraded as a whole. The degradation rates of four selected pollutants are followed: TC > OTC > ETC > EOTC. This indicated that when TCs entered the soil, part of TCs transformed into slower-degraded 4-epimers, and these 4-epimers could also be converted back to their antibiotic parents, causing the long-term residue of TCs in soil. When added to the soil alone, TC and OTC significantly promoted the proliferation of most ARGs and MGEs, among them, trb-C, IS1247 and IS1111 were the top three genes in abundance. ETC and EOTC had little effect at the beginning. However, as the 4-epimers continuously converted into their parents after one month of cultivation, ETC and EOTC treatments showed similar promoting effect on ARGs and MGEs, indicating that the effect of ETC and EOTC on soil resistome was lagged and mainly caused by their transformed parents. Nocardioides, unclassified_Rhizobiaceae, norank_Sericytochromatia, Microlunatus, Solirubrobacter and norank_67-14 were the most frequent hosts of ARGs, Most of which belong to the phylum Actinobacteria. Due to their large transformation to TCs, slow degradation rate and potential effects on soil microbes and ARGs, the harm of TCs’ 4-epimers on soil ecosystem cannot be ignored.

Mesoporous bioactive glasses (MBGs), which belong to the category of modern porous nanomaterials, have garnered significant attention due to their impressive biological activities, appealing physicochemical properties, and desirable morphological features. They hold immense potential for utilization in diverse fields, including adsorption, separation, catalysis, bioengineering, and medicine. Despite possessing interior porous structures, excellent morphological characteristics, and superior biocompatibility, primitive MBGs face challenges related to weak encapsulation efficiency, drug loading, and mechanical strength when applied in biomedical fields. It is important to note that the advantageous attributes of MBGs can be effectively preserved by incorporating supramolecular assemblies, miscellaneous metal species, and their conjugates into the material surfaces or intrinsic mesoporous networks. The innovative advancements in these modified colloidal inorganic nanocarriers inspire researchers to explore novel applications, such as stimuli-responsive drug delivery, with exceptional in-vivo performances. In view of the above, we outline the fabrication process of calcium-silicon-phosphorus based MBGs, followed by discussions on their significant progress in various engineered strategies involving surface functionalization, nanostructures, and network modification. Furthermore, we emphasize the recent advancements in the textural and physicochemical properties of MBGs, along with their theranostic potentials in multiple cancerous and non-cancerous diseases. Lastly, we recapitulate compelling viewpoints, with specific considerations given from bench to bedside.

Abstract The voltage-gated calcium channel CaV1.2 is essential for cardiac and vessel smooth muscle contractility and brain function. Accumulating evidence demonstrates that malfunctions of CaV1.2 are involved in brain and heart diseases. Pharmacological inhibition of CaV1.2 is therefore of therapeutic value. Here, we report cryo-EM structures of CaV1.2 in the absence or presence of the antirheumatic drug tetrandrine or antihypertensive drug benidipine. Tetrandrine acts as a pore blocker in a pocket composed of S6II, S6III, and S6IV helices and forms extensive hydrophobic interactions with CaV1.2. Our structure elucidates that benidipine is located in the DIII-DIV fenestration site. Its hydrophobic sidechain, phenylpiperidine, is positioned at the exterior of the pore domain and cradled within a hydrophobic pocket formed by S5DIII, S6DIII, and S6DIV helices, providing additional interactions to exert inhibitory effects on both L-type and T-type voltage gated calcium channels. These findings provide the structural foundation for the rational design and optimization of therapeutic inhibitors of voltage-gated calcium channels.

Abstract Background This study seeks to investigate the impacts of Lactobacillus reuteri (L. reuteri) on hepatic ischemia-reperfusion (I/R) injury and uncover the mechanisms involved. Methods Mice in the I/R groups were orally administered low and high doses of L.reuteri (L.reuteri-low and L. reuteri-hi; 1 × 1010 CFU/d and 1 × 1011 CFU/d), for 4 weeks prior to surgery. Following this, mice in the model group were treated with an Nrf2 inhibitor (ML-385), palmitoylcarnitine, or a combination of both. Results After treatment with L. reuteri, mice exhibited reduced levels of serum aminotransferase (ALT), aspartate aminotransferase (AST), and myeloperoxidase (MPO) activity, as well as a lower Suzuki score and apoptosis rate. L. reuteri effectively reversed the I/R-induced decrease in Bcl2 expression, and the significant increases in the levels of Bax, cleaved-Caspase3, p-p65/p65, p-IκB/IκB, p-p38/p38, p-JNK/JNK, and p-ERK/ERK. Furthermore, the administration of L. reuteri markedly reduced the inflammatory response and oxidative stress triggered by I/R. This treatment also facilitated the activation of the Nrf2/HO-1 pathway. L. reuteri effectively counteracted the decrease in levels of beneficial gut microbiota species (such as Blautia, Lachnospiraceae NK4A136, and Muribaculum) and metabolites (including palmitoylcarnitine) induced by I/R. Likewise, the introduction of exogenous palmitoylcarnitine demonstrated a beneficial impact in mitigating hepatic injury induced by I/R. However, when ML-385 was administered prior to palmitoylcarnitine treatment, the previously observed effects were reversed. Conclusion L. reuteri exerts protective effects against I/R-induced hepatic injury, and its mechanism may be related to the promotion of probiotic enrichment, differential metabolite homeostasis, and the Nrf2/HO-1 pathway, laying the foundation for future clinical applications.

A landslide inventory is essential for numerous applications, including disaster prevention and mitigation. The emergence of advanced satellite technologies and the proliferation of extensive satellite imagery have greatly enhanced the role of deep learning-based semantic segmentation networks in the development of comprehensive landslide inventories. In deep learning, especially in semantic segmentation tasks, the loss function is crucial to guide the training of neural networks. However, typical loss functions have several challenges and shortcomings, including difficulty in handling objects of different scales and neglecting spatial correlation. These drawbacks hinder semantic segmentation networks from solely concentrating on accurately predicting landslide categories with rich semantic information. The spatial details (e.g. small landslides and precise landslide boundary information) in the segmentation results may be lost, reducing the accuracy of landslide extraction. Most studies only focus on training and detection in the local region. Consequently, detecting new unexplored region and detrimental to emergency response is challenging. This study presents a level set loss-guided semantic segmentation network, which can be integrated with different semantic segmentation networks, to address these issues. Three out of five study areas (e.g. Bijie, Jiuzhaigou, and Taitung) are used for model training and accuracy evaluation, while the rest, which are newly unexplored regions (e.g. Hokkaido and Haiti), are used to test the transferability of the proposed loss function in different regions. The study results validate the effectiveness of the designed level set loss in various semantic segmentation networks and in different study areas for landslide extraction.

Premature ovarian insufficiency (POI) or premature ovarian failure (POF) is a multifactorial disorder occurring in reproductive-age women, characterized by elevated levels of follicle-stimulating hormone (FSH) and irregular or absent menstrual cycles, often accompanied by perimenopausal symptoms and infertility. While assisted reproductive technology can address the reproductive aspirations of some POI-affected women, it is hindered by issues such as exorbitant expenses, substantial risks, and poor rates of conception. Encouragingly, extensive research is exploring novel approaches to enhance fertility, particularly in the realm of stem cell therapy, showcasing both feasibility and significant potential. Human amniotic epithelial cells (hAECs) from discarded placental tissues are crucial in regenerative medicine for their pluripotency, low immunogenicity, non-tumorigenicity, accessibility, and minimal ethical concerns. Preclinical studies highlight the underlying mechanisms and therapeutic effects of hAECs in POI treatment, and current research is focusing on innovative interventions to augment hAECs’ efficacy. However, despite these strides, overcoming application challenges is essential for successful clinical translation. This paper conducted a comprehensive analysis of the aforementioned issues, examining the prospects and challenges of hAECs in POI, with the aim of providing some insights for future research and clinical practice.

Summary: Background: The need for new therapeutics for attention deficit hyperactivity disorder (ADHD) is evident. Brain, cerebrospinal fluid (CSF), and plasma protein biomarkers with causal genetic evidence could represent potential drug targets. However, a comprehensive screen of the proteome has not yet been conducted. Methods: We employed a three-pronged approach using Mendelian Randomization (MR) and Bayesian colocalization analysis. Firstly, we studied 608 brains, 214 CSF, and 612 plasma proteins as potential causal mediators of ADHD using MR analysis. Secondly, we analysed the consistency of the discovered biomarkers across three distinct subtypes of ADHD: childhood, persistent, and late-diagnosed ADHD. Finally, we extended our analysis to examine the correlation between identified biomarkers and Tourette syndrome and pervasive autism spectrum disorder (ASD), conditions often linked with ADHD. To validate the MR findings, we conducted sensitivity analysis. Additionally, we performed cell type analysis on the human brain to identify risk genes that are notably enriched in various brain cell types. Findings: After applying Bonferroni correction, we found that the risk of ADHD was increased by brain proteins GMPPB, NAA80, HYI, CISD2, and HYI, TIE1 in CSF and plasma. Proteins GMPPB, NAA80, ICA1L, CISD2, TIE1, and RMDN1 showed overlapped loci with ADHD risk through Bayesian colocalization. Overexpression of GMPPB protein was linked to an increase in the risk for all three ADHD subtypes. While ICA1L provided protection against both ASD and ADHD, CISD2 increased the probability of both disorders. Cell-specific studies revealed that GMPPB, NAA80, ICA1L, and CISD2 were predominantly present on the surface of excitatory-inhibitory neurons. Interpretation: Our comprehensive MR investigation of the brain, CSF, and plasma proteomes revealed seven proteins with causal connections to ADHD. Particularly, GMPPB and TIE1 emerged as intriguing targets for potential ADHD therapy. Funding: This work was partly funded by the Key R & D Program of Zhejiang (T.L. 2022C03096); the National Natural Science Foundation of China Project (C.Z. 82001413); Postdoctoral Foundation of West China Hospital (C.Z. 2020HXBH163).

Hippo pathway coordinate developmental processes through regulating cell growth, proliferation and programmed death. However, mollusks achieved little focus so far on the role of this significant pathway during larval development. In this study, three core genes, hippo, warts and yorkie, were identified in Haliotis discus hannai. They mainly expressed at trochophore and veliger stages. Positive signals of yorkie occurred near the edge of shell field at the trochophore stage (12 and 15 hpf), then tended to overlap with hippo and warts (18 hpf). In veliger larva after torsion (at 30 hpf), their expression appeared in several non-overlapping areas. These findings suggested their important roles in post-embryonic development. Silencing of yorkie led to 90 % cumulative mortality at 60 h posttreatment, with a 33 %-highest abnormality rate, meanwhile significantly upregulated the relative expression of hippo and warts at 6 h and 12 h posttreatment (P

Background: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment; however, a significant proportion of gastric cancer (GC) patients do not respond to this therapy. Consequently, there is an urgent need to elucidate the mechanisms underlying resistance to ICIs and identify robust biomarkers capable of predicting the response to ICIs at treatment initiation.Methods: In this study, we collected GC tissues from 28 patients prior to the administration of anti-programmed death 1 (PD-1) immunotherapy and conducted protein quantification using high-resolution mass spectrometry (MS). Subsequently, we analyzed differences in protein expression, pathways, and the tumor microenvironment (TME) between responders and non-responders. Furthermore, we explored the potential of these differences as predictive indicators. Finally, using machine learning algorithms, we screened for biomarkers and constructed a predictive model.Results: Our proteomics-based analysis revealed that low activity in the complement and coagulation cascades pathway (CCCP) and a high abundance of activated CD8 T cells are positive signals corresponding to ICIs. By using machine learning, we successfully identified a set of 10 protein biomarkers, and the constructed model demonstrated excellent performance in predicting the response in an independent validation set (N = 14; area under the curve [AUC] = 0.959).Conclusion: In summary, our proteomic analyses unveiled unique potential biomarkers for predicting the response to PD-1 inhibitor immunotherapy in GC patients, which may provide the impetus for precision immunotherapy.

BackgroundSerum lipids were found to be correlated with chronic kidney disease and cardiovascular disease. Here, we aimed to research the potential causal associations between five serum lipid parameters and the risk of diabetic nephropathy using several Mendelian Randomization methods.MethodsGenetic data was obtained from the UK Biobank datasets. Causal effects were estimated using multiple MR methods. Heterogeneity and pleiotropy tests were performed.ResultsMR analysis revealed that HDL-C and TG exhibited causal associations with diabetic nephropathy (P

ObjectiveCandida albicans (C. albicans), an opportunistic pathogen, is implicated in the carcinogenesis of various cancers, thereby significantly impacting human health. This study conducts an in-depth analysis of the prevailing research dynamics concerning the relationship between C. albicans and cancer over the past decade, offering a comprehensive overview of the knowledge structure and emerging focal points in this field through bibliometric scrutiny.MethodsA methodical quantitative and visual scrutiny of pertinent literature from the Web of Science Core Collection (WoSCC) spanning the previous decade was carried out employing VOS Viewer and CiteSpace software.ResultsFrom January 1, 2014, to January 1, 2024, a comprehensive corpus of 1,259 articles was delineated. Prominent research institutions included the Egyptian Knowledge Bank, Cairo University, and King Saud University. The top three prolific countries were the United States, China, and India. Among the authors, Mohamed, Gehad G., Mahmoud, Walaa H., and Netea, Mihai G., emerged as the most prolific, with Pfaller, Ma being distinguished as the most frequently cited author. The journal Molecules published the highest number of articles, while PLoS One had the highest citation count. Nature had the highest impact factor. The research focal points in this field encompassed the interactions between C. albicans and cancer, the correlation with oral cancer, the underlying mechanisms of C. albicans carcinogenic potential, as well as antifungal and anticancer therapies.ConclusionThis investigation constitutes a pioneering bibliometric analysis elucidating the trends and advancements in research regarding the correlation between C. albicans and cancer. Said analyses uncover the prevailing research focal points and trends, offering insightful guidance for subsequent inquiry in this domain.Systematic review registrationhttps://www.webofscience.com/wos/woscc/summary/df33afba-f843-41e8-b932-cb3678eb8243-e92e7316/relevance/1

ObjectivesThis manuscript undertakes a systematic examination of the research landscape concerning global Cryptococcus species and their dynamism with the host immune system spanning the past decade. It furnishes a detailed survey of leading knowledge institutions and critical focal points in this area, utilizing bibliometric analysis.MethodsVOSviewer and CiteSpace software platforms were employed to systematically analyze and graphically depict the relevant literature indexed in the WoSCC database over the preceding ten years.ResultsIn the interval between October 1, 2013, and October 1, 2023, a corpus of 795 publications was amassed. The primary research institutions involved in this study include Duke University, the University of Minnesota, and the University of Sydney. The leading trio of nations, in terms of publication volume, comprises the United States, China, and Brazil. Among the most prolific authors are Casadevall, Arturo; Wormley, Floyd L., Jr.; and Olszewski, Michal A., with the most highly cited author being Perfect, Jr. The most esteemed journal is Mbio, while Infection and Immunity commands the highest citation frequency, and the Journal of Clinical Microbiology boasts the most significant impact factor. Present research foci encompass the intricate interactions between Cryptococcus pathogenesis and host immunity, alongside immune mechanisms, complications, and immunotherapies.ConclusionThis represents the first exhaustive scholarly review and bibliometric scrutiny of the evolving landscapes in Cryptococcus research and its interactions with the host immune system. The analyses delineated herein provide insights into prevailing research foci and trajectories, thus furnishing critical directions for subsequent inquiries in this domain.

BackgroundWith increased life expectancy, cognitive decline has emerged as a prevalent neurodegenerative disorder.ObjectiveThis study aimed to examine the correlation between concentrations of Plasma long-chain n-3 polyunsaturated fatty acids (LCPUFAs) and cognitive performance in elderly Americans.MethodsData were analyzed from older adults enrolled in two NHANES cycles. Participants completed four cognitive assessments, including the Immediate Recall Test (IRT), Delayed Recall Test (DRT), Animal Fluency Test (AFT), and Digit Symbol Substitution Test (DSST). Linear regression and restricted cubic spline modeling examined associations between plasma LCPUFAs levels and cognitive test outcomes.ResultsThe cohort included 610 adults aged 69 years on average, 300 (49.2%) males and 310 (50.8%) females. The median LCPUFAs concentration was 309.4 μmol/L, with an interquartile range of 244.7–418.9 μmol/L. In unadjusted and adjusted generalized linear regression model analyses, circulating LCPUFAs exhibited significant positive correlations with DRT performance. No relationships were detected among those with chronic conditions (chronic heart failure, stroke, diabetes). A significant association between LCPUFAs levels and DRT scores was evident in males but not females.ConclusionPlasma LCPUFAs concentrations were significantly associated with DRT performance in males free of chronic illnesses, including heart failure, stroke, and diabetes.

ABSTRACT: Qingyuan partridge chicken (QYM) is a highly regarded native breed in China, highly esteemed for its exceptional breeding characteristics. However, the investigation into the selection signatures and its strains remains largely unexplored. In this study, blood sampling, DNA extracting, and high-depth resequencing were performed in 27 QYMs. Integrating the genomic data of 14 chicken (70 individuals) breeds from other researches, to analyze the genetic structure, selection signatures, and effects of selective breeding within QYM and its 3 strains (QYMA, QYMB, and QYMC). Population structure analysis revealed an independent QYM cluster, which exhibited distinct from other breeds, with each of its 3 strains displaying distinct clustering patterns. Linkage disequilibrium analysis highlighted QYMB's notably slower decay rate, potentially influenced by selection pressure from various production indicators. Examination of selection signatures uncovered genes and genetic mechanisms associated with genomic changes resulting from extensive selective breeding within the QYM and its strains. Intriguingly, diacylglycerol kinase beta (DGKB) and catenin alpha 2 (CTNNA2) were identified as commonly selected genes across the 3 QYM strains, linked to energy metabolism, muscle development, and fat metabolism. Our research validates the substantial impact of selective breeding on QYM and its strains, concurrently identifying genomic regions and signaling pathways associated with their distinctive characters. This research also establishes a fundamental framework for advancing yellow-feathered broiler breeding strategies.

Abstract This study aimed to investigate the correlation between serum uric acid (UA) and gestational diabetes mellitus (GDM) during the first trimester and provide a new perspective for the prevention and treatment of GDM. Based on the diagnostic criteria of gestational diabetes of the International Association of Diabetes and Pregnancy Study Groups, 1744 and 4256 patients were enrolled in the GDM and normal glucose tolerance (NGT) groups. Four groups were constituted based on the quartile of first-trimester serum UA (UA) level, and the differences in each indicator between groups were compared. Logistic regression was used to analyze the effects of UA level on GDM risk. The rate of GDM in the UA quartile changed from low to high. Significant differences were also observed in fasting plasma glucose level, 1 h post glucose and 2 h post glucose levels, in all the groups (P

Abstract Background There are very limited reports on anti-metabolic glutamate receptor5 (mGluR5) encephalitis, especially lacking of pediatric research. The disease was mostly accompanied by tumors, mainly Hodgkin's lymphoma. No reports of other tumors, such as gangliocytoma have been reported to associate with anti-mGluR5 encephalitis so far. Case presentation and literature reviews We reported a case of a 12-year-old boy with anti-mGluR5 encephalitis complicated with gangliocytoma. The patient suffered from mental disorders including auditory hallucination, and sleep disorders. His cranial magnetic resonance imaging (MRI) showed an abnormality in the right insular lobe. Autoimmune encephalitis antibodies testing was positive for mGluR5 IgG antibody both in cerebrospinal fluid and serum (1:3.2, 1:100 respectively). Abdominal CT indicated a mass in left retroperitoneal confirmed with gangliocytoma via pathology. The patient underwent resection of gangliocytoma. After first-line immunotherapy (glucocorticoid, gamma globulin), his condition was improved. Furthermore, we provide a summary of 6 pediatric cases of Anti-mGluR5 encephalitis. Most of them complicated with Hodgkin's lymphoma, except the case currently reported comorbid with gangliocytoma. The curative effect is satisfactory. Conclusions We report the first patient with anti-mGlur5 encephalitis complicated with gangliocytoma. It suggests that in addition to paying attention to the common lymphoma associated with anti-mGlur5 encephalitis, we should also screen the possibility of other tumors for early detection of the cause, active treatment and prevention of recurrence.

Abstract The vehicle's power battery is composed of a large number of battery cells series or in parallel. Due to the manufacturing process error and the different use environments, there are differences between the battery cells, and the battery pack will have inconsistency problems, which will increase the safety hazard. Therefore, it is of great practical significance to identify and warn about the inconsistency of power batteries. Based on the data of the internet of vehicles platform, this paper proposes an improved isolated forest power battery abnormal monomer identification and early warning method, which uses the sliding window (SW) to segment the dataset and update the data of the diagnosis model in real‐time. The scores of normal battery cells and abnormal battery cells were analyzed, and then the fault threshold was determined to be 0.75. The results show that the recall ratio and precision ratio of the algorithm are 0.91 and 0.95, respectively, which is more suitable for inconsistent battery cell identification than other methods. If the SW size is 15, the warning effect is the best. Before the vehicle alarm occurs, the algorithm can realize early fault warnings, thus effectively avoiding the safety problems caused by inconsistency faults.

Optimizing the aerodynamic structure of composite insulators can guarantee the safe operation of power systems. In this study, we construct a simulation model for composite insulator contaminant deposition using the COMSOL simulation software, and the rationality of the simulation model and method is verified through wind tunnel experiments. Taking the FXBW4-110/100 composite insulator as an example, we adopt a progressive optimization plan to explore the impacts of shed spacing s, and shed inclination angles α and β on its contaminant deposition characteristics under DC and AC voltages. Based on the numerical simulation results, we analyze the antifouling performance of insulators before and after structural optimization. The results indicate the following: 1) The contaminant deposition of the insulator under AC and DC voltages is negatively correlated with the shed spacing s, but positively correlated with the lower inclination angle β. 2) Under AC voltages, the contaminant deposition of the insulator increases with the upper inclination angle α, while under DC voltages, the contaminant deposition shows an uptrend first, then a downtrend and then an uptrend again with the increase of the upper inclination angle α. 3) Compared with the original model, the AC-optimized model ( α = 6°, β = 2° and s = 98 mm) with a larger shed spacing s, and smaller shed inclination angles α and β showed superior antifouling performance at wind speeds of no less than 2 m/s, and under the typical conditions ( v = 2.5 m/s, d = 20 μm, and ρ = 2 200 kg/m 3), its contaminant deposition is 15% less than that of the original model ( α = 10°, β = 2° and s = 80 mm).

In this work, a novel heterojunction composite Ag2S/KTaxNb1-xO3 was designed and synthesized through a combination of hydrothermal and precipitation procedures. The Ta/Nb ratio of the KTaxNb1-xO3 and the Ag2S content were optimized. The best 0.5% Ag2S/KTa0.5Nb0.5O3 (KTN) sample presents an enhanced photocatalytic performance in ammonia synthesis than KTN and Ag2S. Under simulated sunlight, the NH3 generation rate of 0.5% Ag2S/KTN reaches 2.0 times that of pure KTN. Under visible light, the reaction rate ratio of the two catalysts is 6.0. XRD, XPS, and TEM analysis revealed that Ag2S was intimately decorated on the KTN nanocubes surface, which promoted the electron transfer between the two semiconductors. The band structure investigation indicated that the Ag2S/KTN heterojunction established a type-II band alignment with intimate contact, thus realizing the effective transfer and separation of photogenerated carriers. The change in charge separation was considered as the main reason for the enhanced photocatalytic performance. Interestingly, the Ag2S/KTN composite exhibited higher NH3 generation performance under the combined action of ultrasonic vibration and simulated sunlight. The enhanced piezo-photocatalytic performance can be ascribed that the piezoelectric effect of KTN improved the bulk separation of charge carriers in KTN. This study not only provides a potential catalyst for photocatalytic nitrogen fixation but also shows new ideas for the design of highly efficient catalysts via semiconductor modification and external field coupling.

Abstract Schizophrenia has been linked to polymorphism in genes encoding components of the complement system, and hyperactive complement activity has been linked to immune dysfunction in schizophrenia patients. Whether and how specific complement components influence brain structure and cognition in the disease is unclear. Here we compared 52 drug-naïve patients with first-episode schizophrenia and 52 healthy controls in terms of levels of peripheral complement factors, cortical thickness (CT), logical memory and psychotic symptoms. We also explored the relationship between complement factors with CT, cognition and psychotic symptoms. Patients showed significantly higher levels of C1q, C4, factor B, factor H, and properdin in plasma. Among patients, higher levels of C3 in plasma were associated with worse memory recall, while higher levels of C4, factor B and factor H were associated with thinner sensory cortex. These findings link dysregulation of specific complement components to abnormal brain structure and cognition in schizophrenia.

Abstract Cis-peptide bonds are rare in proteins, and building blocks less favorable to the trans-conformer have been considered destabilizing. Although proline tolerates the cis-conformer modestly among all amino acids, for collagen, the most prevalent proline-abundant protein, all peptide bonds must be trans to form its hallmark triple-helix structure. Here, using host-guest collagen mimetic peptides (CMPs), we discover that surprisingly, even the cis-enforcing peptoid residues (N-substituted glycines) form stable triple-helices. Our interrogations establish that these peptoid residues entropically stabilize the triple-helix by pre-organizing individual peptides into a polyproline-II helix. Moreover, noting that the cis-demanding peptoid residues drastically reduce the folding rate, we design a CMP whose triple-helix formation can be controlled by peptoid cis-trans isomerization, enabling direct targeting of fibrotic remodeling in myocardial infarction in vivo. These findings elucidate the principles of peptoid cis-trans isomerization in protein folding and showcase the exploitation of cis-amide-favoring residues in building programmable and functional peptidomimetics.

Abstract Nonomuraea gerenzanensis (N. gerenzanensis) is known for its ability to biosynthesize A40926, the precursor of the glycopeptide antibiotic (GPA) Dalbavancin. However, challenges and uncertainties related to the genetic manipulation of the rare actinomycetes remain. In order to improve the conjugation transfer of N. gerenzanensis, the crucial factors affecting conjugal transfer were evaluated, including agar medium, mycelial state, donor-recipient ratio, magnesium ion concentration, and antibiotic coverage time firstly. Additionally, γ-butyrolactone (GBL) for quorum sensing (QS) and antibiotics targeting bacterial walls were applied to evaluate their effects on conjugation transfer. As a result, the optimal conditions of 5%TSB of liquid medium, 24 h of the period time, V0.1 of agar medium, 30 mM of magnesium ion, the ratio 10:1 of donor-to-recipient, and 27 h of the overlaying time of antibiotic were determined. Furthermore, the results showed that autoinducer GBL and GPA teicoplanin had a synergetic effect on the conjugation transfer of N. gerenzanensis at a working concentration of 60 µM and 0.5 µg mL−1, respectively. The highest conjugation efficiency could reach about 1.3 depending on the optimal process conditions and the interference of QS and antibiotics.

Abstract Background Soil microbial fuel cells (MFCs) can remove antibiotics and antibiotic resistance genes (ARGs) simultaneously, but their removal mechanism is unclear. In this study, metagenomic analysis was employed to reveal the functional genes involved in degradation, electron transfer and the nitrogen cycle in the soil MFC. Results The results showed that the soil MFC effectively removed tetracycline in the overlapping area of the cathode and anode, which was 64% higher than that of the control. The ARGs abundance increased by 14% after tetracycline was added (54% of the amplified ARGs belonged to efflux pump genes), while the abundance decreased by 17% in the soil MFC. Five potential degraders of tetracycline were identified, especially the species Phenylobacterium zucineum, which could secrete the 4-hydroxyacetophenone monooxygenase encoded by EC 1.14.13.84 to catalyse deacylation or decarboxylation. Bacillus, Geobacter, Anaerolinea, Gemmatirosa kalamazoonesis and Steroidobacter denitrificans since ubiquinone reductase (encoded by EC 1.6.5.3), succinate dehydrogenase (EC 1.3.5.1), Coenzyme Q-cytochrome c reductase (EC 1.10.2.2), cytochrome-c oxidase (EC 1.9.3.1) and electron transfer flavoprotein-ubiquinone oxidoreductase (EC 1.5.5.1) served as complexes I, II, III, IV and ubiquinone, respectively, to accelerate electron transfer. Additionally, nitrogen metabolism-related gene abundance increased by 16% to support the microbial efficacy in the soil MFC, and especially EC 1.7.5.1, and coding the mutual conversion between nitrite and nitrate was obviously improved. Conclusions The soil MFC promoted functional bacterial growth, increased functional gene abundance (including nitrogen cycling, electron transfer, and biodegradation), and facilitated antibiotic and ARG removal. Therefore, soil MFCs have expansive prospects in the remediation of antibiotic-contaminated soil. This study provides insight into the biodegradation mechanism at the gene level in soil bioelectrochemical remediation.

In order to obtain candidate strains with strong colonization ability and excellent fermentation performance of goji berry juice, 3 strains of lactic acid bacteria were isolated and screened from human intestinal tract. They were identified by morphological, physiological and biochemical, 16S rDNA sequence analysis and phylogenetic tree construction, and their acid resistance, bile salt resistance, artificial gastric fluid, intestinal fluid resistance and fermentation performance were studied. The results showed that all three strains were identified as Pediococcus lactis, numbered NXU_220218, NXU_220219 and NXU_220220, respectively. The growth rate from 2 to 8 h, the ability of NXU 220218 to produce acid was stronger, and the tolerance to acid, bile salt and artificial gastric juice was better than NXU 220219 and NXU 220220. The survival rate of NXU_220218 was 67% at pH2, 65% in bovine bile salt at 0.3% concentration, 72% tolerance to artificial gastric juice, and 95% tolerance to artificial intestinal juice. Finally, the NXU_220218 strain was inoculated and used in the preparation of fermented goji berry juice. It was found that the reducing sugar content and the free radical scavenging rate in the fermented goji berry juice were significantly reduced and increased, respectively, compared with the unfermented goji berry juice, indicating that the NXU_220218 strain had good fermentation performance for goji berry juice and could be used as a candidate strain of lactic acid bacteria for the fermentation of goji berry juice.

To better understand the effects of agronomic practices on yield–nutrition relationships in wheat (Triticum aestivum L.) grains for Zn biofortification while improving yields simultaneously, effects of different soil fertilization and different drone-based foliar spraying treatments were investigated in calcareous soils. For soil fertilization, the incorporation of Zn or increasing the N/P ratio in compound fertilizers proved to be effective in enhancing grain Zn concentrations and yields. However, the overall effects of soil fertilization are limited, with a maximal yield increase of only 7.0% and a maximal increase of the grain Zn concentration from 19.4 to 27.0 mg/kg, which is far below the target biofortification value of 40–50 mg/kg. Unfortunately, there was a negative side effect, which decreased Fe and Mn concentrations and the Fe bioavailability. Notably, drone-based foliar Zn sprayings increased grain yields from the control 7.5 t/ha to 8.6 t/ha at ZnO treatment by 12.0% and 8.8 t/ha at ZnSO4·7H2O treatment by 17.3%. Meanwhile, grain Zn concentrations were increased from the control 33.5 mg/kg to 41.9 mg/kg at ZnO treatment by 25.1% and 43.6 mg/kg at ZnSO4·7H2O treatment by 30.1%. Treatments with ZnSO4·7H2O increased grain Zn concentrations and accumulation more so than ZnO, indicating the importance of chemical Zn forms in determining the effectiveness of foliar spraying. Moreover, foliar Zn sprayings simultaneously increased grain concentrations and accumulation of Fe, Mn and Cu, demonstrating multiple benefits. There were positive correlations between Zn and Fe, Mn or Cu, indicating synergistic interactions. Compared to micronutrients, concentrations of grain macronutrients (N, P, K, Ca and Mg) were less affected. Thus, a dual-benefit in both grain yields and micronutrient (particularly for Zn) nutrition could be effectively achieved through appropriate soil fertilization and foliar Zn spraying. These findings provide a better understanding of the yield–nutrition relationship among wheat grain yields, Zn and other nutrient elements for a better integrated manipulation to achieve a win–win situation in yield and nutrition.

Background Elevated platelet count (PLTc) is associated with first-episode schizophrenia and adverse outcomes in individuals with precursory psychosis. However, the impact of antipsychotic medications on PLTc and its association with symptom improvement remain unclear.Aims We aimed to investigate changes in PLTc levels following antipsychotic treatment and assess whether PLTc can predict antipsychotic responses and metabolic changes after accounting for other related variables.Methods A total of 2985 patients with schizophrenia were randomised into seven groups. Each group received one of seven antipsychotic treatments and was assessed at 2, 4 and 6 weeks. Clinical symptoms were evaluated using the positive and negative syndrome scale (PANSS). Additionally, we measured blood cell counts and metabolic parameters, such as blood lipids. Repeated measures analysis of variance was used to examine the effect of antipsychotics on PLTc changes, while structural equation modelling was used to assess the predictive value of PLTc on PANSS changes.Results PLTc significantly increased in patients treated with aripiprazole (F=6.00, p=0.003), ziprasidone (F=7.10, p

Previous studies have demonstrated an association between lymphatic vessels and diseases caused by bacterial infections. Listeria monocytogenes (LM) bacterial infection can affect multiple organs, including the intestine, brain, liver and spleen, which can be fatal. However, the impacts of LM infection on morphological and functional changes of lymphatic vessels remain unexplored. In this study, we found that LM infection not only induces meningeal and mesenteric lymphangiogenesis in mice, but also impairs meningeal lymphatic vessels (MLVs)-mediated macromolecules drainage. Interestingly, we found that the genes associated with lymphatic vessel development and function, such as Gata2 and Foxc2, were downregulated, suggesting that LM infection may affect cellular polarization and valve development. On the other hand, photodynamic ablation of MLVs exacerbated inflammation and bacterial load in the brain of mice with LM infection. Overall, our findings indicate that LM infection induces lymphangiogenesis and may affect cell polarization, cavity formation, and valve development during lymphangiogenesis, ultimately impairing MLVs drainage.

The biocurrent generated by soil extracellular electron transfer (EET) partly drives biogeochemical cycles and controls soil quality. However, it is unclear how the soil abiotic and biotic conditions affect the biocurrent conduction. In this study, the response relationship of soil microenvironment and in-situ biocurrent was studied. The results showed that red soil exhibited the optimal electron transfer efficiency, as evidenced by the maximum current density and accumulated charge output, with increments of 56–93 % and 80–2800 %, respectively, compared with the other five types of soils. Soil physicochemical properties were the most important factor on the biocurrent generation, and further the quantity and bioavailability of dissolved organic matter, NH4+-N content, and lower pH were predictive indicators for the exoelectrogenic processes of soils. In addition, the high soil biocurrent was likely determined by a complex synergistic network of the transformation of carbon and nitrogen, electroactive bacteria involving the functions of cell wall/membrane and cytochrome enzyme metabolism and transport related EET process. Overall, we provide an insight into the relationship among soil biocurrent conduction, physicochemical properties, bacteria community and metabolic function, and a support for bioelectrochemical technology application.

ABSTRACT: Waterfowl have a high likelihood of being infected with Riemerella anatipestifer. Although the pathogen is found in domestic ducks, turkeys, geese, and wild birds, there is little information available about the consequences of infection during egg laying and hatching in chickens. Here, we present the first report of a novel sequence type of R. anatipestifer S63 isolated from chickens in China. On the basis of pan-genome analysis, we showed S63′s genome occupies a distinct branch with other R. anatipestifer isolates from other hosts. Galleria mellonella larval tests indicated that S63 is less virulent than R. anatipestifer Ra36 isolated from ducks. Ducks and hens are susceptible to S63 infection. There is no mortality rate for chickens or ducks, but adult chickens experience neurological symptoms that reduce egg production and hatching rates. In chickens, S63 might be passed vertically from parents to offspring, resulting in ''jelly-like'' lifeless embryos. Using quantitative PCR, S63 was detected in the brain, liver, reproductive organs, and embryos. As far as we know, this is the first report of R. anatipestifer in hens, a disease that can reduce egg productivity, lower hatching rates, and produce jelly-like lifeless embryos, and the first report to raise the possibility that hens can be infected by roosters via semen.

PurposeThe purpose of this study is to develop an intelligent diagnosis model based on the LASSO method to predict the severity of COVID-19 patients.MethodsThe study uses the clinical data of 500 COVID-19 patients from a designated hospital in Suzhou, China, and selects eight features, including age, sex, dyspnea, comorbidity, complication, lymphocytes (LYM), CRP, and lung injury score, as the most important predictors of COVID-19 severity. The study applies the LASSO method to perform feature selection and regularization, and compares the LASSO method with other machine learning methods, such as ridge regression, support vector machine, and random forest.ResultsThe study finds that the ridge regression model has the best performance among the four models, with an AUROC of 0.92 in the internal validation and 0.91 in the external validation.ConclusionThe study provides a simple, robust, and interpretable model for the intelligent diagnosis of COVID-19 severity, and a convenient and practical tool for the public and the health care workers to assess COVID-19 severity. However, the study also has some limitations and directions for future research, such as the need for more data from different sources and settings, and from prospective, longitudinal, multi-class classification models. The study hopes to contribute to the prevention and control of COVID-19, and to the improvement of the diagnosis and treatment of COVID-19 patients.