Search

The adipose tissue surrounding blood vessels is known as perivascular adipose tissue (PVAT), which represents a distinct ectopic fat depot that adheres to the majority of the vasculature. In recent years, owing to its unique location and function, PVAT has been regarded as a new type of adipose tissue distinct from traditional visceral fat. It releases adipokines with vasoconstrictive functions, which regulate vascular function through paracrine and endocrine mechanisms. Interestingly, PVAT can be categorized as white, brown or a mixture of both depending on its anatomical location. Brown adipose tissue (BAT) is located adjacent to the thoracic aorta in rodents, while a mix of brown and white tissue surrounds the abdominal aorta. PVAT exhibits regional phenotypic differences in different parts of the vasculature bed, which may lead to heterogeneity in the secretion profiles and norepinephrine (NE) content in regional PVAT and subsequently affect the regulation of specific adipokine signaling pathways in regional PVAT, resulting in differences in the regulation of vascular function. The aim of this review was to explore the potential factors that influence the anticontractile function of regional PVAT in the vasculature, including the heterogeneity of regional PVAT, the anticontractile function mediated by endothelial nitric oxide synthase (eNOS) in regional PVAT, the activity of the adiponectin-eNOS pathway in regional PVAT adipocytes, and the concentration of the sympathetic neurotransmitter NE in regional PVAT.

BackgroundAt present, the available evidence regarding the relationship between duration of phenoxybenzamine use and postoperative delirium is inadequate in suspected adrenal pheochromocytoma.ObjectiveTo understand how changes in the duration of phenoxybenzamine use may affect postoperative delirium. The secondary objective of this study is to explore how the duration of phenoxybenzamine use may jointly influence postoperative delirium together with other interacting variables.MethodsWe conducted a retrospective cohort study involving 527 participants with a preoperative diagnosis of suspected pheochromocytoma. CT characteristics, preoperative preparation, intraoperative infusion, estimated bleeding, use of intraoperative vasoactive drugs, and outcomes were obtained from all participants. Logistic regression and interaction effects were utilized to substantiate the research objectives.ResultsA total of 108 (20.5%) developed postoperative delirium, which was seen in 37 (18.0%) in the pheochromocytoma group and 71 (22.0%) in the non-pheochromocytoma group. The incidence of postoperative delirium showed no statistically significant differences in the two groups. A positive association between the duration of phenoxybenzamine use and the risk of postoperative delirium was observed (OR = 1.05, 95%CI = 1.03–1.08, p

ObjectiveTo investigate how Chinese residents perceived changes in their protective behaviors in the early stage after the lifting of the dynamic zero-COVID policy, and to explore the associations between the overall perceived change and factors such as demographic and health-related information, COVID-19 related perceptions, negative emotions, and coping styles.MethodsThis cross-sectional study involved 798 Chinese residents who completed an online questionnaire between 16 and 25 December 2022. The questionnaire covered demographic and health-related information, COVID-19 related perceptions, negative emotions, coping styles, and perceived changes in protective behaviors. Multiple linear stepwise regression analysis was used to determine the factors associated with the overall perceived change in protective behaviors.ResultsThe mean score for perceived protective behavioral change among participants was 61.38 (SD = 10.20), which was significantly higher than the hypothesized no-change value of 49 (p

The chestnut tree exhibits self-incompatibility, where the selection of the male parent (pollen xenia) significantly affects seed starch metabolism, as well as fruit yield and quality. Despite its importance, the molecular mechanisms underlying pollen xenia remains largely unknown. In this study, we utilized the ‘Lan You’ variety of C. mollissima to construct a high-quality reference genome. As a result, a first Telomere-to-telomere (T2T) gap-free genome for this species was successfully assembled. A total of 560 transcription factors and 22 structural genes were identified as consistent across the TO-GCNs, indicating a consistent regulation pattern in the co-expression of genes involved in starch accumulation. These networks were further divided into three sub-networks: T1, T2, and T3. Among these, the T1 and T2 sub-networks exhibited a higher number of structural genes with consistent regulation patterns and were closely associated with sugar biosynthesis. The gene SBE (Camol08G0254600) was identified as the hub gene with the highest degree of connectivity, encoding a key rate-limiting enzyme in the amylopectin biosynthesis pathway. This study provides a foundation for further research on C. mollissima population genetics, genetic improvement, and strategies aimed at enhancing yield and quality.

ObjectivesThis study describes the detection and tracking of emergency neurosurgical cross-transmission infections with carbapenem-resistant Klebsiella oxytoca (CRKO).MethodsWe conducted an epidemiological investigation and a rapid screening of 66 surveillance samples using the chromogenic selective medium. Two CRKO isolates from infected patients and three from the preoperative shaving razors had similar resistance profiles identified by the clinical laboratory.ResultsThe whole genome sequencing (WGS) results identified all isolates as Klebsiella michiganensis (a species in the K. oxytoca complex) with sequence type 29 (ST29) and carrying resistance genes blaKPC-2 and blaOXY-5, as well as IncF plasmids. The pairwise average nucleotide identity values of 5 isolates ranged from 99.993% to 99.999%. Moreover, these isolates displayed a maximum genetic difference of 3 among 5,229 targets in the core genome multilocus sequence typing scheme, and the razors were confirmed as the contamination source. After the implementation of controls and standardized shaving procedures, no new CRKO infections occurred.ConclusionContaminated razors can be sources of neurosurgical site infections with CRKO, and standard shaving procedures need to be established. Chromogenic selective medium can help rapidly identify targeted pathogens, and WGS technologies are effective mean in tracking the transmission source in an epidemic or outbreak investigation. Our findings increase the understanding of microbial transmission in surgery to improve patient care quality.

BackgroundThe modified Glasgow Prognosis Score (mGPS), which considers both inflammatory response and nutritional status, has been linked to the prognosis of various tumors. The relationship between mGPS and non-small cell lung cancer (NSCLC) patients receiving immune checkpoint inhibitors (ICIs) is still a subject of debate. This meta-analysis aims to comprehensively assess the association between mGPS and survival in NSCLC treated with ICIs.MethodsA thorough review of studies from PubMed, Web of Science, Scopus, and Embase was conducted up to June 4, 2024. Fixed-effect or random-effect models were employed, combining hazard ratios (HRs) and 95% confidence intervals (CI), to assess the prognostic value of mGPS for OS and PFS in patients with NSCLC receiving immunotherapy.ResultsA total of 1,022 patients from 11 studies were recruited. Combined results showed that mGPS elevation was significantly associated with poor OS (HR = 1.63, 95%CI: 1.42-1.87, P < 0.01) and PFS (HR = 1.71, 95%CI: 1.31-2.24, P < 0.01). Subgroup analysis and sensitivity analysis further determined the predictive effect of elevated mGPS on OS and PFS deterioration in NSCLC patients receiving immunotherapy.ConclusionmGPS can be used as a good noninvasive biomarker to demonstrate prognostic and clinical significance in patients with NSCLC undergoing immunotherapy.Systematic review registrationhttp://www.crd.york.ac.uk/prospero/ PROSPERO, identifier CRD42023432661.

BackgroundAnxiety disorders are a significant global mental health concern, contributing to substantial disability-adjusted life years (DALYs) and imposing considerable social and economic burdens. Understanding the epidemiology of anxiety disorders within the BRICS nations (Brazil, Russian Federation, India, China, and South Africa) is essential due to their unique socio-economic landscapes and ongoing transformations.MethodsThis study utilized data from the Global Burden of Disease (GBD) 2021 database to evaluate anxiety disorder incidence trends in BRICS countries from 1992 to 2021. The Age-Period-Cohort (APC) model with an intrinsic estimator (IE) algorithm was employed to disentangle the effects of age, period, and cohort on incidence rates. Data were categorized into 5-year age groups, and 95% uncertainty intervals (UIs) were calculated to account for data variability.ResultsFrom 1992 to 2021, the global number of anxiety disorders cases increased by 73.44%, with age-standardized incidence rates rising by 21.17%. Among BRICS nations, India experienced the largest increase in cases (113.30%), while China had the smallest increase (2.79%). Globally, young (15–49 years) and oldest (80–94 years) age groups showed predominantly positive local drift values, indicating rising incidence rates. Brazil and India mirrored this trend, while China and South Africa mostly exhibited negative local drift values. Russia Federation had mixed trends with younger groups showing negative and older groups positive local drift values. The incidence of anxiety disorders exhibited an “M-shaped” age pattern with peaks at 10–14 and 35–39 years. Period effects were stable globally but varied in BRICS countries, with Brazil showing a decline and India an increase. Cohort effects were stable globally but showed increasing trends in Brazil and India post-1955–1959 cohort.ConclusionThis study highlights a significant increase in anxiety disorders incidence globally and within BRICS nations over the past three decades, with marked variations across countries. The distinct trends observed in age, period, and cohort effects call for age-specific and gender-sensitive mental health policies. Continuous monitoring, research, and tailored public health strategies are essential to address the rising burden of anxiety disorders and improve mental health outcomes in these rapidly evolving regions.

The STING (Stimulator of Interferon Genes) pathway is pivotal in activating innate immunity, making it a promising target for cancer immunotherapy. STING agonists have shown potential in enhancing immune responses, particularly in tumors resistant to traditional therapies. This scholarly review examines the diverse categories of STING agonists, encompassing CDN analogues, non-CDN chemotypes, CDN-infused exosomes, engineered bacterial vectors, and hybrid structures of small molecules-nucleic acids. We highlight their mechanisms, clinical trial progress, and therapeutic outcomes. While these agents offer significant promise, challenges such as toxicity, tumor heterogeneity, and delivery methods remain obstacles to their broader clinical use. Ongoing research and innovation are essential to overcoming these hurdles. STING agonists could play a transformative role in cancer treatment, particularly for patients with hard-to-treat malignancies, by harnessing the body’s immune system to target and eliminate cancer cells.

Suicidal ideation is a desire, thought, or conception that is closely associated with suicide, which is an important risk factor for suicidal behavior. Negative life events may impact college students’ suicidal ideation. According to the suicide susceptibility-stress model, the interaction between susceptibility factors and stressors may influence college students’ suicidal ideation. The present study investigated the role of entity theory and meaning in life in the influence of negative life events on suicidal ideation among college students. A nationwide questionnaire survey was conducted among 938 college students. The Beck Scale for Suicide Ideation, the Implicit Personality Theory Questionnaire, the Adolescent Life Events Scale, and the Meaning in Life Questionnaire were used. The results showed that negative life events were positively correlated with suicidal ideation, entity theory played a mediating role, and meaning in life moderated the mediation of entity theory. Finally, meaning in life and entity theory may bring some benefits to college students; that is, when faced with negative life events, meaning in life and entity theory may attenuate students’ suicidal ideation.

The treatment of the sequelae of severe foot injuries caused by motorcycle spoke injury, especially in pediatric patients, allows for new options and surgical protocols. The tarsometatarsal joint and the first metatarsal were reconstructed by precise preoperative design using the TSF space external fixation technique in one stage to correct the foot deformity and restore the volume and length, and free grafting of the fibular head with epiphysis in the second stage. This method is the first of its kind reported. The patient’s foot deformity was corrected, walking, walking up and down stairs, and running functions were achieved, and the bone quality could grow with age. The combination of TSF six-axis spatial external fixation technique and microscopic technique can maximize the patient’s appearance and function and is worth promoting.

Although the data-driven static voltage stability problems have been widely studied, most of the classical algorithms focus more on improving the accuracy of the system prediction, ignoring the error classification errors generated during the prediction process. Furthermore, current research ignores the utilization of data-driven voltage stability assessment of energy storage systems. Therefore, this paper proposes a static voltage stability assessment method for photovoltaic energy storage systems based on considering the error classification constraint algorithm using Neyman-Pearson umbrella algorithms. Firstly, the Spearman Correlation Coefficient is employed in the feature selection phase. Secondly, an updated voltage stability assessment (VSA) model is proposed. Compared with the existing data-driven prediction of system static voltage stability in the literature, it can realize voltage stability assessment more quickly. Furthermore, on the basis of rapid voltage stability assessment, the umbrella NP classifier can also effectively limit the first-class error and attenuate the effect of error classification by mirroring the control of the number of cycle splits and the type I classification error threshold. Finally, the simulation and experimental results show that the effectiveness and robustness of the scheme proposed in this paper in grid-connected photovoltaic energy farms.

BackgroundHigh-risk double-expressor diffuse large B-cell lymphoma has an inferior prognosis following standard first-line therapy. After failure of second-line therapy, treatment options are limited if accompanied by localized compressive symptoms. Chimeric Antigen Receptor T cell (CAR-T) therapy preceded by bridging radiotherapy may be an effective emerging therapy.Case presentationWe report a 66-year-old female patient diagnosed with stage IV double-expressor diffuse large B-cell lymphoma. The patient achieved progressive disease after two cycles of rituximab, cyclophosphamide, liposomal doxorubicin, vincristine, and prednisone and continued to develop cervical lymph node recurrence after second-line therapy. The patient was infused with CAR-T cells after receiving focal bridging radiotherapy and remained in complete response more than 9 months after treatment. In addition, the patients did not experience serious adverse reactions related to radiotherapy as well as CAR-T cell therapy.ConclusionsIn this article, we describe a patient with double-expressor diffuse large B-cell lymphoma with localized compression symptoms after second-line treatment failure who benefited from CAR-T combined with focal bridging radiotherapy.

Extraskeletal Ewing’s sarcoma (ES) has been reported to originate from various sites. Primary endobronchial ES is an extremely rare bronchial tumor, especially multifocal lesions. This report describes a rare presentation of primary bronchial ES in a 31-year-old female who was referred to the emergency department of our hospital due to suspicion of a foreign body in the bronchus. Computed tomography and bronchoscopy revealed multiple polypoid nodules in the middle bronchus of her right lung, thus excluding the initial diagnosis. Infection-related laboratory tests and serum tumor markers were normal. The bronchial sleeve resection was performed to remove the tumor completely and the patient’s clinical symptoms obviously improved. Subsequent imaging, histopathological, immunohistochemical and genetic analyses made a conclusive diagnosis of primary endobronchial ES. To our knowledge, this is the eighth case of primary bronchial ES reported in medical literature.

The lungs, as vital organs in the human body, continuously engage in gas exchange with the external environment. The lung microbiota, a critical component in maintaining internal homeostasis, significantly influences the onset and progression of diseases. Beneficial interactions between the host and its microbial community are essential for preserving the host’s health, whereas disease development is often linked to dysbiosis or alterations in the microbial community. Evidence has demonstrated that changes in lung microbiota contribute to the development of major chronic lung diseases, including chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), asthma, and lung cancer. However, in-depth mechanistic studies are constrained by the small scale of the lung microbiota and its susceptibility to environmental pollutants and other factors, leaving many questions unanswered. This review examines recent research on the lung microbiota and lung diseases, as well as methodological advancements in studying lung microbiota, summarizing the ways in which lung microbiota impacts lung diseases and introducing research methods for investigating lung microbiota.

BackgroundStatins, being the primary pharmacological intervention for hypercholesterolemia, exhibit a notable degree of interpatient variability in their effectiveness, which may be associated with gut microbiota. This study sought to identify the biomarkers for evaluating differences in statin efficacy.MethodsA quasi case-control study was conducted among participants with hypercholesterolemia and coronary heart disease taking rosuvastatin essential. According to the level of low density lipoprotein cholesterol (LDL-C), participants was divided into the “Up to standard” (US) group and the “Below standard” (BS) group. 16S rDNA sequencing and untargeted metabolomics were applied to detected the information of gut microbiota and related metabolites.ResultsA total of 8 US and 8 BS group matched by age and sex were included in the final analysis. 16S rDNA sequencing results indicated that the characteristic strains of the US group were f-Eubacterium_coprostanoligenes and g-Papillibacter, while the characteristic flora of the BS group were o-C0119, g-Pseudolabrys, s-Dyella-Marensis and f-Xanthobacaceae. Metabolomic results suggested that the levels of chenodeoxycholic acid-3-β-D-glucuronide, 1-methylnicotinamide and acetoacetate in stool samples of the US group were significantly higher than those of the BS group. By identifying the differentially abundant bacterial taxa, the gut microbiota could modulate the efficacy of statins through producing enzymes involved in cholesterol metabolism.ConclusionsThe findings suggest that the difference in statin efficacy may be related to gut microbiota strains that can produce short-chain fatty acids and secondary bile acids and affect the efficacy of statins by regulating the activities of cholesterol metabolite-related proteins. Metabolites related to short-chain fatty acids and secondary bile acids in the gut are expected to be biomarkers indicating the efficacy of statins.

Grain albumin is highly nutritious and closely related to the processing quality of wheat. However, few studies have explored the grain albumin content (GAC) in wheat. This study aims to uncover quantitative trait loci (QTLs) linked to wheat GAC by analyzing a doubled haploid (DH) population derived from common wheat cultivars ShanNong23 and ZhouMai17. We detected six QTLs controlling GAC on chromosomes 1B, 5A, and 6D, with individual QTL explaining 5.78% to 22.29% of the GAC variation. The effect of QGac.cau-1B.1 on GAC is attributed to the presence of the 1BL/1RS translocation, indicating that the 1BL/1RS translocation increase of GAC compared with the non-1BL/1RS translocation lines. The higher GAC observed in 1BL/1RS lines could be primarily attributed to the increased accumulation of omega-secalin, omega-gliadin, low molecular weight glutenin subunit and ribosomal protein content. Additionally, we also found that the SDS-sedimentation value of whole wheat flour was decreased by adding albumin solution. These results advance our understanding of the genetic basis of GAC and offer novel perspectives for enhancing wheat quality through genetic enhancements.

IntroductionSalinity and droughts are severe abiotic stress factors that limit plant growth and development. However, the differences and similarities of non-structural carbohydrates (NSCs) responses patterns of trees under the two stress conditions remain unclear.MethodsWe determined and compared the growth, physiology, and NSCs response patterns and tested the relationships between growth and NSCs concentrations (or pool size) of Eucommia ulmoides seedlings planted in field under drought and salt stress with different intensities and durations.Results and discussionWe found that drought and salt stress can inhibit the growth of E. ulmoides, and E. ulmoides tended to enhance its stress resistance by increasing proline concentration and leaf thickness or density but decreasing investment in belowground biomass in short-term stress. During short-term drought and salt stress, the aboveground organs showed different NSCs response characteristics, while belowground organs showed similar change characteristics: the starch (ST) and NSCs concentrations in the coarse roots decreased, while the ST and soluble sugar (SS) concentrations in the fine roots increased to enhance stress resistance and maintain water absorption function. As salt and drought stress prolonged, the belowground organs represented different NSCs response patterns: the concentrations of ST and SS in fine roots decreased as salt stress prolonged; while ST in fine roots could still be converted into SS to maintain water absorption as drought prolonged, resulting in an increase of SS and a decrease of ST. Significant positive relationships were found between growth and the SS and total NSCs concentrations in leaves and branches, however, no significant correlations were found between growth and below-ground organs. Moreover, relationships between growth and NSCs pool size across organs could be contrast.ConclusionOur results provide important insights into the mechanisms of carbon balance and carbon starvation and the relationship between tree growth and carbon storage under stress, which were of great significance in guiding for the management of artificial forest ecosystem under the context of global change.

Phosphorus (P) is a crucial macronutrient for plant growth and development, and low-Pi stress poses a significant limitation to maize production. While the role of the SPX domain in encoding proteins involved in phosphate (Pi) homeostasis and signaling transduction has been extensively studied in other model plants, the molecular and functional characteristics of the SPX gene family members in maize remain largely unexplored. In this study, we identified six SPX members, and the phylogenetic analysis of ZmSPXs revealed a close relationship with SPX genes in rice. The promoter regions of ZmSPXs were abundant in biotic and abiotic stress-related elements, particularly associated with various hormone signaling pathways, indicating potential intersections between Pi signaling and hormone signaling pathways. Additionally, ZmSPXs displayed tissue-specific expression patterns, with significant and differential induction in anthers and roots, and were localized to the nucleus and cytoplasm. The interaction between ZmSPXs and ZmPHRs was established via yeast two-hybrid assays. Furthermore, overexpression of ZmSPX1 enhanced root sensitivity to Pi deficiency and high-Pi conditions in Arabidopsis thaliana. Phenotypic identification of the maize transgenic lines demonstrated the negative regulatory effect on the P concentration of stems and leaves as well as yield. Notably, polymorphic sites including 34 single-nucleotide polymorphisms (SNPs) and seven insertions/deletions (InDels) in ZmSPX1 were significantly associated with 16 traits of low-Pi tolerance index. Furthermore, significant sites were classified into five haplotypes, and haplotype5 can enhance biomass production by promoting root development. Taken together, our results suggested that ZmSPX family members possibly play a pivotal role in Pi stress signaling in plants by interacting with ZmPHRs. Significantly, ZmSPX1 was involved in the Pi-deficiency response verified in transgenic Arabidopsis and can affect the Pi concentration of maize tissues and yield. This work lays the groundwork for deeper exploration of the maize SPX family and could inform the development of maize varieties with improved Pi efficiency.

ObjectiveAcute unilateral vestibulopathy (AUVP) is the second leading cause of peripheral vestibular vertigo. Full recovery of AUVP is related to sufficient central vestibular compensation. It has been confirmed that the vestibular nucleus and vestibular cortex are involved in the process of vestibular compensatory in AUVP patients. However, few studies have focused on the functional compensation of thalamus in patients with AUVP. This study aimed to explore the alterations of resting-state functional connectivity (FC) focused on thalamus using functional magnetic resonance imaging (fMRI) in AUVP patients.MethodsData of 3D-T1 and resting-state fMRI were collected from 40 AUVP patients and 35 healthy controls (HC). Seeds-based (bilateral thalamus) FC was analyzed to investigate the changes in FC between the two groups. Furthermore, we evaluated the associations between altered thalamus FC and clinical features in AUVP patients using Pearson’s partial correlation.ResultsCompared with HC, AUVP patients showed decreased FC between bilateral thalamus and left insula. We also observed decreased FC between right thalamus and left supramarginal gyrus. Additionally, we found increased FC between left thalamus and right postcentral gyrus (PCG), as well as increased FC between right thalamus and regions of bilateral PCG, right middle frontal gyrus and right middle occipital gyrus in AUVP patients. Furthermore, the FC between left thalamus and left insula was negatively correlated with values of canal paresis in patients with AUVP (p = 0.010, r = −0.434).ConclusionOur results provided first evidence for the decreased thalamo-vestibular cortex pathway, as well as increased thalamo-somatosensory and thalamo-visual cortex pathway in AUVP patients. These findings help us better understand the underlying mechanisms of central dynamic compensatory following an acute unilateral peripheral vestibular damage.

BackgroundPolatuzumab vedotin, the first FDA-approved antibody-drug conjugate (ADC) targeting CD79b, is utilized in the treatment of previously untreated diffuse large B-cell lymphoma (DLBCL) or high-grade B-cell lymphoma (HGBL), as well as relapsed or refractory (R/R) DLBCL. Despite its approval, concerns persist regarding the long-term safety profile of polatuzumab vedotin. This study aims to evaluate the adverse events (AEs) associated with polatuzumab vedotin since its approval in 2019, utilizing data mining strategies applied to the FDA Adverse Event Reporting System (FAERS).MethodsSignal detection employed four methodologies, including reporting odds ratio (ROR), proportional reporting ratio (PRR), bayesian confidence propagation neural network (BCPNN), and multi-item gamma poisson shrinker (MGPS), to evaluate and quantify the signals of polatuzumab vedotin-associated AEs. Additionally, subgroup analyses based on patients age, gender, and fatal cases were conducted to investigate AEs occurrences in specific subpopulations.ResultsA total of 1,521 reports listing polatuzumab vedotin as a “principal suspect (PS)” drug were collected from the FAERS database. Through concurrent compliance with four algorithms, 19 significant Standardized MedDRA Query (SMQ) AEs and 92 significant Preferred Term (PT) AEs were detected. Subgroup analyses revealed a higher incidence of PTs in male patients compared to female patients, increased likelihood of polatuzumab vedotin-associated AEs in elder patients (>65 years), and AEs with a high risk of fatal cases include: blood lactate dehydrogenase increased, cytopenia, and hydronephrosis. The median time to AEs occurrence following polatuzumab vedotin initiation was 18.5 (5∼57.75) days, with 95% of AEs occurred within 162 days.ConclusionThis study identified various AEs associated with polatuzumab vedotin, offering critical insights for clinical monitoring and risk identification in patients receiving polatuzumab vedotin therapy.

The Eocene was a typical greenhouse climate period in the history of the Earth, with a high global sea level and extensive carbonate deposits developed in Tethys. During the Eocene, a carbonate platform was deposited in the western Tarim Basin, which belongs to the easternmost Tethys. However, the details of this carbonate platform and its complications for paleoecology and paleoclimate are still unclear. This research focuses on the bivalve-bearing carbonates of the Kalataer Formation in the western Tarim Basin, and detailed analyses of microfacies, biostratigraphy, paleoecology, and sea-level change were carried out. The bivalves of the Kalataer Formation are dominated by the Ostrea (Turkostrea) strictiplicata, Ostrea (Turkostrea) cizancourti, Ostrea (Turkostrea) strictiplicata, Ostrea (Turkostrea) strictiplicata, and Sokolowia buhsii, and the age is middle Lutetian of the Eocene. The biota of the Kalataer Formation mainly lives in open shallow sea environments, with medium to low energy and rich nutrients and oxygen, representing a typical shallow marine ecosystem of the carbonate platform. Microfacies and paleoecology indicate a large marine transgression event occurred in the western Tarim Basin during the middle Eocene.

IntroductionTo analyze the influencing factors for progression from newly diagnosed prediabetes (PreDM) to diabetes within 3 years and establish a prediction model to assess the 3-year risk of developing diabetes in patients with PreDM.MethodsSubjects who were diagnosed with new-onset PreDM at the Physical Examination Center of the First Affiliated Hospital of Soochow University from October 1, 2015 to May 31, 2023 and completed the 3-year follow-up were selected as the study population. Data on gender, age, body mass index (BMI), waist circumference, etc. were collected. After 3 years of follow-up, subjects were divided into a diabetes group and a non-diabetes group. Baseline data between the two groups were compared. A prediction model based on logistic regression was established with nomogram drawn. The calibration was also depicted.ResultsComparison between diabetes group and non-diabetes group: Differences in 24 indicators including gender, age, history of hypertension, fatty liver, BMI, waist circumference, systolic blood pressure, diastolic blood pressure, fasting blood glucose, HbA1c, etc. were statistically significant between the two groups (P0.05). Logistic regression analysis showed that ageing, elevated BMI, male gender, high fasting blood glucose, increased LDL-C, fatty liver, liver dysfunction were risk factors for progression from PreDM to diabetes within 3 years (P

IntroductionHospital affiliated green spaces can help patients recover and recover their physical functions, promote physical and mental relaxation, enhance health awareness, and improve overall health. However, there are still significant questions about how to scientifically construct hospital affiliated green spaces. This study examines the impact of hospital green spaces on patient rehabilitation through scientific evaluation methods, providing reference for the scientific construction of hospital affiliated green spaces. Applicability evaluation was conducted on the affiliated green spaces of three hospitals in Harbin. An evaluation system covering plants, space, accessibility, rehabilitation functions, and promotional and educational functions has been constructed. The entropy weight method is used to determine the weight of indicators, and the grey correlation analysis method is used to evaluate the suitability of green space for patient rehabilitation.MethodsThe experimental results showed that the landscape accessibility index had the highest weight (0.3005) and the plant index had the lowest weight (0.1628), indicating that caring for special needs is the foundation of hospital landscapes, and plants have subtle and long-term effects on physical and mental health. In the evaluation of the rehabilitation applicability of the affiliated green spaces of various hospitals, the second hospital has the highest grey correlation degree (0.8525), followed by the tumor hospital (0.5306) and the fifth hospital (0.4846). It can be seen that the green space of the second hospital has high applicability for patient rehabilitation, but the green space of the tumor hospital and the fifth hospital needs to be improved and developed.Results and discussionThe evaluation criteria used in this study are comprehensive. The landscaping at the Third Hospital is well-planned with good plant configuration and reasonable spatial layout. However, there is insufficient consideration for accessibility in the landscape design, and the details are lacking. The rehabilitation and educational functions of the landscape are inadequate, with limited outdoor activities and low road safety. The hospital′s affiliated green spaces should adhere to the principle of “appropriate scale, comprehensive functionality, and educational leisure,” integrating rehabilitation and educational functions while increasing the variety of outdoor activities. In the future, emphasis should be placed on exploring the integration of landscape and rehabilitation to provide a functional site that is convenient for visiting, with improved rehabilitation facilities and an educational and enjoyable environment. The design should incorporate elements that contribute to a sense of well-being, including roads and

This study aimed to develop and validate a bone marrow edema model using a magnetic resonance imaging-based radiomics nomogram for the diagnosis of osteoarthritis. Clinical and magnetic resonance imaging (MRI) data of 302 patients with and without osteoarthritis were retrospectively collected from April 2022 to October 2023 at Longhua Hospital affiliated with the Shanghai University of Traditional Chinese Medicine. The participants were randomly divided into two groups (a training group, n = 211 and a testing group, n = 91). We used logistic regression to analyze clinical characteristics and established a clinical model. Radiomics signatures were developed by extracting radiomic features from the bone marrow edema area using MRI. A nomogram was developed based on the rad-score and clinical characteristics. The diagnostic performance of the three models was compared using the receiver operating characteristic curve and Delong’s test. The accuracy and clinical application value of the nomogram were evaluated using calibration curve and decision curve analysis. Clinical characteristics such as age, radiographic grading, Western Ontario and McMaster Universities Arthritis Index score, and radiological features were significantly correlated with the diagnosis of osteoarthritis. The Rad score was constructed from 11 radiological features. A clinical model was developed to diagnose osteoarthritis (training group: area under the curve [AUC], 0.819; testing group: AUC, 0.815). Radiomics models were used to effectively diagnose osteoarthritis (training group,: AUC, 0.901; testing group: AUC, 0.841). The nomogram model composed of Rad score and clinical characteristics had better diagnostic performance than a simple clinical model (training group: AUC, 0.906; testing group: AUC, 0.845; p < 0.01). Based on DCA, the nomogram model can provide better diagnostic performance in most cases. In conclusion, the MRI-bone marrow edema-based radiomics-clinical nomogram model showed good performance in diagnosing early osteoarthritis.

BackgroundThe current clinical practice lacks sufficient objective indicators for evaluating thyroid-associated ophthalmopathy (TAO). This study aims to quantitatively assess TAO by evaluating levator palpebrae superioris (LPS) using Dixon-T2WI.MethodsThe retrospective study included 231 eyes (119 patients) in the TAO group and 78 eyes (39 volunteers) in the normal group. Dixon-T2WI provided data on maximum thickness of LPS (LPS_T) and signal intensity ratio (LPS_SIR) between the muscle and ipsilateral brain white matter. TAO diagnosis and assessment of its activity and severity were quantitatively determined using LPS_T and LPS_SIR.ResultsIn the TAO group, LPS_T and LPS_SIR were higher than those in the normal group (p < 2.2e-16). The upper lid retraction (ULR) ≥ 2 mm group exhibited higher LPS_T and LPS_SIR compared to the ULR < 2 mm and normal groups. Optimal diagnostic performance was achieved with an AUC of 0.91 for LPS_T (cutoff: 1.505 mm) and 0.81 for LPS_SIR (cutoff: 1.170). LPS_T (p = 2.8e-07) and LPS_SIR (p = 3.9e-12) in the active phase were higher than in the inactive phase. LPS_T and LPS_SIR showed differences among the mild, moderate-to-severe, and sight-threatening groups (p < 0.05). ROC showed an AUC of 0.70 for LPS_T (cutoff: 2.095 mm) in judging the active phase, and 0.78 for LPS_SIR (cutoff: 1.129). For judging the moderate-to-severe and above, AUC was 0.76 for LPS_T (cutoff: 2.095 mm) and 0.78 for LPS_SIR (cutoff: 1.197).ConclusionThe maximum thickness and SIR of LPS provide imaging indicators for assisting in the diagnosis and quantitative evaluation of TAO.

Myasthenia gravis (MG) is an antibody-mediated autoimmune disease with a prevalence of 150–250 cases per million individuals. Autoantibodies include long-lived antibodies against the acetylcholine receptor (AChR), mainly of the IgG1 subclass, and IgG4, produced almost exclusively by short-lived plasmablasts, which are prevalent in muscle-specific tyrosine kinase (MuSK) myasthenia gravis. Numerous investigations have demonstrated that MG patients receiving conventional medication today still do not possess satisfactory symptom control, indicating a substantial disease burden. Subsequently, based on the type of the autoantibody and the pathogenesis, we synthesized the published material to date and reached a conclusion regarding the literature related to personalized targeted therapy for MG. Novel agents for AChR MG have shown their efficacy in clinical research, such as complement inhibitors, FcRn receptor antagonists, and B-cell activating factor (BAFF) inhibitors. Rituximab, a representative drug of anti-CD20 therapy, has demonstrated benefits in treatment of MuSK MG patients. Due to the existence of low-affinity antibodies or unidentified antibodies that are inaccessible by existing methods, the treatment for seronegative MG remains complicated; thus, special testing and therapy considerations are necessary. It may be advantageous to initiate the application of novel biologicals at an early stage of the disease. Currently, therapies can also be combined and individualized according to different types of antibodies. With such a wide range of drugs, how to tailor treatment strategies to patients with various conditions and find the most suitable solution for each MG profile are our necessary and urgent aims.

In high-altitude environments characterized by low pressure and oxygen levels, the intestinal microbiota undergoes significant alterations. Whether individuals are subjected to prolonged exposure or acute altitude changes, these conditions lead to shifts in both the diversity and abundance of intestinal microbiota and changes in their composition. While these alterations represent adaptations to high-altitude conditions, they may also pose health risks through certain mechanisms. Changes in the intestinal microbiota induced by high altitudes can compromise the integrity of the intestinal mucosal barrier, resulting in gastrointestinal dysfunction and an increased susceptibility to acute mountain sickness (AMS). Moreover, alterations in the intestinal microbiota have been implicated in the induction or exacerbation of chronic heart failure. Targeted modulation of the intestinal microbiota holds promise in mitigating high-altitude-related cardiac damage. Dietary interventions, such as adopting a high-carbohydrate, high-fiber, low-protein, and low-fat diet, can help regulate the effects of intestinal microbiota and their metabolic byproducts on intestinal health. Additionally, supplementation with probiotics, either through dietary sources or medications, offers a means of modulating the composition of the intestinal microbiota. These interventions may offer beneficial effects in preventing and alleviating AMS following acute exposure to high altitudes.

Owning to their extreme environmental conditions, lakes on the Qinghai-Tibet Plateau have typically displayed a simplistic food web structure, rendering them more vulnerable to climate change compared to lakes in plains. Phytoplankton, undergoing a changing aquatic environment, play a crucial role in the material cycle and energy flow of the food chain, particularly important for the unique fish species of the Tibetan Plateau. To identify the changing environment indexes and determine the response of phytoplankton composition to the environment change in alpine lakes, three lakes—Lake Qinghai, Lake Keluke and Lake Tuosu—were selected as study areas. Seasonal sampling surveys were conducted in spring and summer annually from 2018 to 2020. Our findings revealed there were significant changes in physicochemical parameters and phytoplankton in the three lakes. Bacillariophyta was the predominant phytoplankton in Lake Qinghai from 2018 to 2020, with the genera Synedra sp., Navicula sp., Cymbella sp. and Achnanthidium sp. predominated alternately. Lake Keluke alternated between being dominated by Bacillariophyta and cyanobacteria during the same period. Dolichospermum sp., a cyanobacteria, was prevalent in the summer of 2018 and 2019 and in the spring of 2020. In Lake Tuosu, Bacillariophyta was the predominant phytoplankton from 2018 to 2020, except in the summer of 2019, which was dominated by cyanobacteria. Synedra sp., Oscillatoria sp., Pseudoanabaena sp., Chromulina sp. and Achnanthidium sp. appeared successively as the dominant genera. Analysis revealed that all three lakes exhibited higher phytoplankton abundance in 2018 that in 2019 and 2020. Concurrently, they experienced higher average temperatures in 2018 than in the subsequent years. The cyanobacteria, Bacillariophyta, Chlorophyta and overall phytoplankton increased with temperature and decreased with salinity and NH4-N. Besides, the ratios of cyanobacteria, and the ratios of Bacillariophyta accounted in total phytoplankton increased with temperature. These findings suggest that cyanobacteria and phytoplankton abundance, especially Bacillariophyta, may have an increase tendency in the three alpine lakes under warm and wet climate.

Williams syndrome (WS) is characterized by a range of clinical features, including cardiovascular disease, distinctive facial traits, neurobehavioral disorders, and a condition known as transient infantile hypercalcemia. Among these, endocardial calcification represents a non-specific response to severe, etiologically diverse myocardial injuries. In this report, we document a unique case involving an infant with WS who exhibited rapidly progressive arterial stenosis and left ventricular endocardial calcification, associated with a novel heterozygous deletion. While arterial stenosis is the most frequently observed cardiovascular issue in WS, instances of endocardial calcification during infancy are exceedingly rare and have not previously been reported in the context of WS.

BackgroundFood safety has always been a major concern for people, and frequent food safety incidents pose a serious threat to people’s health and safety. To identify high-risk patterns in the field of food safety and assist regulatory authorities in scientifically managing food safety risks, this study aims to evaluate food safety risks from multiple dimensions and provide a scientific basis for formulating targeted food safety management measures.MethodsThe risk matrix method, along with the Borda method, is used to evaluate food safety risks. Based on the constructed food safety incident database, the risk matrix method is applied for static risk assessment from seven aspects: food categories, years, provinces, incident entities, causes, pollution sources, and links, and for dynamic risk assessment in different provinces.ResultsThe top five food categories in risk ranking are meat and meat products, fruits and vegetables, grain and grain products, other category, and aquatic products. Food safety risks show an increasing trend year by year, with the years 2006, 2012-2015 and 2019 having higher risk rankings. The top three provinces in risk ranking are Hunan, Guangdong, and Shaanxi. The top four entities in risk ranking are restaurants, enterprises, households, and canteens. The top four causes in risk ranking are human intention, human error, mismanagement, and production and social environment. The top four pollution sources in risk ranking include chemical pollution, other pollution, biological pollution, and food additives. The top three links in risk ranking include production and processing link, catering link, and agricultural production link. Across provinces, food safety risks in the years 2012-2015 are generally higher compared to other years, with the highest number of high-risk provinces in 2014.ImplicationThe findings of this study have significant implications for food safety management in China. By implementing food safety risk prevention and control countermeasures proposed, China can strengthen its food safety management framework, reduce the incidence of food safety incidents, and safeguard the health and well-being of its population.

Myasthenia gravis (MG) stands as a perplexing autoimmune disorder affecting the neuromuscular junction, driven by a multitude of antibodies targeting postsynaptic elements. However, the mystery of MG pathogenesis has yet to be completely uncovered, and its heterogeneity also challenges diagnosis and treatment. Growing evidence shows the differential expression of non-coding RNAs (ncRNAs) in MG has played an essential role in the development of MG in recent years. Remarkably, these aberrantly expressed ncRNAs exhibit distinct profiles within diverse clinical subgroups and among patients harboring various antibody types. Furthermore, they have been implicated in orchestrating the production of inflammatory cytokines, perturbing the equilibrium of T helper 1 cells (Th1), T helper 17 cells (Th17), and regulatory T cells (Tregs), and inciting B cells to generate antibodies. Studies have elucidated that certain ncRNAs mirror the clinical severity of MG, while others may hold therapeutic significance, showcasing a propensity to return to normal levels following appropriate treatments or potentially foretelling the responsiveness to immunosuppressive therapies. Notably, the intricate interplay among these ncRNAs does not follow a linear trajectory but rather assembles into a complex network, with competing endogenous RNA (ceRNA) emerging as a prominent hub in some cases. This comprehensive review consolidates the landscape of dysregulated ncRNAs in MG, briefly delineating their pivotal role in MG pathogenesis. Furthermore, it explores their promise as prospective biomarkers, aiding in the elucidation of disease subtypes, assessment of disease severity, monitoring therapeutic responses, and as novel therapeutic targets.

IntroductionPlant bacterial wilt is an important worldwide disease caused by Ralstonia solanacearum which is a complex of species.MethodsIn this study, we identified and sequenced the genome of R. solanacearum strain gd-2 isolated from tobacco.ResultsStrain gd-2 was identified as R. solanacearum species complex (RSSC) phylotype I sequevar 15 and exhibited strong pathogenicity to tobacco. The genome size of gd-2 was 5.93 Mb, including the chromosomes (3.83 Mb) and the megaplasmid (2.10 Mb). Gene prediction results showed that 3,434 and 1,640 genes were identified in the chromosomes and plasmids, respectively. Comparative genomic analysis showed that gd-2 exhibited high conservation with ten highly similar strain genomes and the differences between gd-2 and other genomes were mainly located at positions GI12-GI14. 72 type III effectors (T3Es) were identified and RipAZ2 was a T3E specific to gd-2 compared with other eight sequenced strain.DiscussionOur study provides a new basis and evidence for studying the pathogenic mechanism of R. solanacearum.

IntroductionAnaplastic lymphoma kinase (ALK)-positive large B-cell lymphoma (LBCL) is a rare subtype of diffuse large B-cell lymphoma (DLBCL). Patients with ALK+ LBCLs have poor response and survival outcomes when treated with traditional chemotherapy regiments. The efficacy of second- and third-generation ALK inhibitors has been reported in treating ALK+ LBCLs. Additionally, owing to the plasmablastic morphology and immune features observed in ALK+ LBCLs, plasma cell tumor therapies may be effective for this patient population. In this case report, we utilized a myeloma-like therapy combined with a third-generation ALK inhibitor for a newly diagnosed ALK+ LBCL patient.Case presentationWe reported a 32-year-old male patient diagnosed with ALK+ LBCL. Immunohistochemistry (IHC) analysis revealed a plasma cell immunophenotype characterized by CD138 positivity but negativity for mature B lymphocyte markers. The patient received six cycles of VRD (bortezomib 1.3 mg/m2 d1, 4, 8, and 11; lenalidomide 25 mg qd d1–14; dexamethasone 20 mg d1–2, d4–5, d8–9, and d11–12) and cyclophosphamide (1.0 g q3w) treatment. Lorlatinib (100 mg once daily) was added starting from the second cycle of treatment onwards. After four cycles of treatment, the patient achieved complete remission, which was maintained for more than 6 months after completing chemotherapy, without any significant safety concerns.ConclusionVRD and cyclophosphamide combined with a third-generation ALK inhibitor resulted in durable complete remission for an individual with ALK+ LBCL, suggesting it as a therapeutic option for patients with this subtype.

With the advancement of low-carbon distribution networks, the heightened stochasticity introduced by a multitude of renewable energy sources in the power grid has significantly augmented the regulatory challenges faced by the power grid. Dispatching distributed resources emerges as an effective solution to this issue. However, these resources often lack observability and controllability, hindering their participation in power regulation services. To establish a reliable interaction between distributed resources and power grids, the deployment of numerous edge sensing terminals becomes essential, albeit incurring high costs. In light of this, our paper proposes a dynamic network planning method for edge sensing terminals based on node differentiation and resource observability criteria, aiming to facilitate real-time and dependable observation of distributed resources. Initially, the node weight, a metric to gauge the disparity among nodes, is computed, considering communication quality deviation, resource development synergy, and the distribution of distributed resources. Subsequently, an optimal configuration method is introduced, accounting for the terminal’s reliability under faults. Lastly, a method for dynamic terminal networking planning is presented, gradually reducing the depth of unobservable resources. An enhanced genetic algorithm is employed to address this challenge. This method was validated using an IEEE 33 node system and a 91 node actual system, demonstrating significant effectiveness in reducing terminal configuration costs.

ObjectiveTo assess changes in static and dynamic functional network connectivity (sFNC and dFNC) and explore their correlations with clinical features in benign paroxysmal positional vertigo (BPPV) patients with residual dizziness (RD) after successful canalith repositioning maneuvers (CRM) using resting-state fMRI.MethodsWe studied resting-state fMRI data from 39 BPPV patients with RD compared to 38 BPPV patients without RD after successful CRM. Independent component analysis and methods of sliding window and k-means clustering were adopted to investigate the changes in dFNC and sFNC between the two groups. Additionally, temporal features and meta-states were compared between the two groups. Furthermore, the associations between fMRI results and clinical characteristics were analyzed using Pearson’s partial correlation analysis.ResultsCompared with BPPV patients without RD, patients with RD had longer duration of BPPV and higher scores of dizziness handicap inventory (DHI) before successful CRM. BPPV patients with RD displayed no obvious abnormal sFNC compared to patients without RD. In the dFNC analysis, patients with RD showed increased FNC between default mode network (DMN) and visual network (VN) in state 4, the FNC between DMN and VN was positively correlated with the duration of RD. Furthermore, we found increased mean dwell time (MDT) and fractional windows (FW) in state 1 but decreased MDT and FW in state 3 in BPPV patients with RD. The FW of state 1 was positively correlated with DHI score before CRM, the MDT and FW of state 3 were negatively correlated with the duration of BPPV before CRM in patients with RD. Additionally, compared with patients without RD, patients with RD showed decreased number of states and state span.ConclusionThe occurrence of RD might be associated with increased FNC between DMN and VN, and the increased FNC between DMN and VN might potentially correlate with the duration of RD symptoms. In addition, we found BPPV patients with RD showed altered global meta-states and temporal features. These findings are helpful for us to better understand the underlying neural mechanisms of RD and potentially contribute to intervention development for BPPV patients with RD.

Seasonal environmental shifts and improper eating habits are the important causes of diarrhea in children and growing animals. Whether adjusting feeding time at varying temperatures can modify cecal bacterial structure and improve diarrhea remains unknown. Three batches growing rabbits with two groups per batch were raised under different feeding regimens (fed at daytime vs. nighttime) in spring, summer and winter separately, and contents were collected at six time points in 1 day and used 16S rRNA sequencing to investigate the effects of feeding regimens and season on the composition and circadian rhythms of cecum bacteria. Randomized forest regression screened 12 genera that were significantly associated with seasonal ambient temperature changes. Nighttime feeding reduced the abundance of the conditionally pathogenic bacteria Desulfovibrio and Alistipes in summer and Campylobacter in winter. And also increases the circadian rhythmic Amplicon Sequence Variants in the cecum, enhancing the rhythm of bacterial metabolic activity. This rhythmic metabolic profile of cecum bacteria may be conducive to the digestion and absorption of nutrients in the host cecum. In addition, this study has identified 9 genera that were affected by the combination of seasons and feeding time. In general, we found that seasons and feeding time and their combinations affect cecum composition and circadian rhythms, and that daytime feeding during summer and winter disrupts the balance of cecum bacteria of growing rabbits, which may adversely affect cecum health and induce diarrhea risk.

IntroductionObstructive sleep apnea (OSA) is a common sleep-related breathing disorder, and has become a serious threat to public health. Intermittent hypoxia caused by OSA results in a low-grade inflammatory response that leads to impaired mucosal barrier function. Claudin (CLDN) molecules are important for the permeability of the mucosal epithelium. This study aimed to explore whether CLDN molecules can be a potential biomarker of OSA.MethodsA total of 37 healthy controls and 40 OSA patients underwent a physical assessment for OSA and filled out the STOP-Bang Questionnaire (SBQ) and Epworth Sleepiness Scale (ESS). Clinical specimens of plasma and urine were obtained to observe the difference between OSA patients and healthy controls and diagnostic accuracy of CLDN molecules for OSA.ResultsCLDN1, CLDN2, and CLDN3 molecules in plasma and urine decreased in OSA patients (both p < 0.05). The areas under the receiver operating characteristic curve (AUCs) of urinary CLDN1, plasma CLDN1, urinary CLDN2, plasma CLDN2, urinary CLDN3, and plasma CLDN3 were 0.887, 0.724, 0.779, 0.676, 0.828, and 0.665, respectively. The AUC of urinary CLDN1 + CLDN2 + CLDN3 was 0.906 (95% confidence interval (CI), 0.831–0.981). The AUC of plasma CLDN1 + CLDN2 + CLDN3 was 0.776 (95% CI, 0.645–0.878). The AUC of urinary CLDN3 + SBQ was 0.899 (95% CI, 0.832–0.967). The AUC of urinary CLDN3 + ESS was 0.896 (95% CI, 0.826–0.966). In addition, Urinary CLDN-3 was negative associated with the severity of OSA.ConclusionCLDN molecules are promising as useful biomarkers for OSA, which may be related to the impaired barrier function related to OSA.

Background: Emerging evidence points to the exceptional importance and value of m7G alteration in the diagnosis and prognosis of cancers. Nonetheless, a biomarker for precise screening of various cancer types has not yet been developed based on serum m7G-harboring miRNAs.Methods: A total of 20,702 serum samples, covering 12 cancer types and consisting of 7,768 cancer samples and 12,934 cancer-free samples were used in this study. A m7G target miRNA diagnostic signature (m7G-miRDS) was established through the least absolute shrinkage and selection operator (LASSO) analyses in a training dataset (n = 10,351), and validated in a validation dataset (n = 10,351).Results: The m7G-miRDS model, a 12 m7G-target-miRNAs signature, demonstrated high accuracy and was qualified for cancer detection. In the training and validation cohort, the area under the curve (AUC) reached 0.974 (95% CI 0.971–0.977) and 0.972 (95% CI 0.969–0.975), respectively. The m7G-miRDS showed superior sensitivity in each cancer type and had a satisfactory AUC in identifying bladder cancer, lung cancer and esophageal cancer. Additionally, the diagnostic performance of m7G-miRDS was not interfered by the gender, age and benign disease.Conclusion: Our results greatly extended the value of serum circulating miRNAs and m7G in cancer detection, and provided a new direction and strategy for the development of novel biomarkers with high accuracy, low cost and less invasiveness for mass cancer screening, such as ncRNA modification.

Preeclampsia is one of the leading causes of maternal and fetal morbidity and mortality worldwide. Preeclampsia is linked to mitochondrial dysfunction as a contributing factor in its progression. This study aimed to develop a novel diagnostic model based on mitochondria-related genes(MRGs) for preeclampsia using machine learning and further investigate the association of the MRGs and immune infiltration landscape in preeclampsia. In this research, we analyzed GSE75010 database and screened 552 DE-MRGs between preeclampsia samples and normal samples. Enrichment assays indicated that 552 DE-MRGs were mainly related to energy metabolism pathway and several different diseases. Then, we performed LASSO and SVM-RFE and identified three critical diagnostic genes for preeclampsia, including CPOX, DEGS1 and SH3BP5. In addition, we developed a novel diagnostic model using the above three genes and its diagnostic value was confirmed in GSE44711, GSE75010 datasets and our cohorts. Importantly, the results of RT-PCR confirmed the expressions of CPOX, DEGS1 and SH3BP5 were distinctly increased in preeclampsia samples compared with normal samples. The results of the CIBERSORT algorithm revealed a striking dissimilarity between the immune cells found in preeclampsia samples and those found in normal samples. In addition, we found that the levels of SH3BP5 were closely associated with several immune cells, highlighting its potential involved in immune microenvironment of preeclampsia. Overall, this study has provided a novel diagnostic model and diagnostic genes for preeclampsia while also revealing the association between MRGs and immune infiltration. These findings offer valuable insights for further research and treatment of preeclampsia.

Sepsis is a global health concern accounting for more than 1 in 5 deaths worldwide. Sepsis is now defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Sepsis can develop from bacterial (gram negative or gram positive), fungal or viral (such as COVID) infections. However, therapeutics developed in animal models and traditional in vitro sepsis models have had little success in clinical trials, as these models have failed to fully replicate the underlying pathophysiology and heterogeneity of the disease. The current understanding is that the host response to sepsis is highly diverse among patients, and this heterogeneity impacts immune function and response to infection. Phenotyping immune function and classifying sepsis patients into specific endotypes is needed to develop a personalized treatment approach. Neutrophil-endothelium interactions play a critical role in sepsis progression, and increased neutrophil influx and endothelial barrier disruption have important roles in the early course of organ damage. Understanding the mechanism of neutrophil-endothelium interactions and how immune function impacts this interaction can help us better manage the disease and lead to the discovery of new diagnostic and prognosis tools for effective treatments. In this review, we will discuss the latest research exploring how in silico modeling of a synergistic combination of new organ-on-chip models incorporating human cells/tissue, omics analysis and clinical data from sepsis patients will allow us to identify relevant signaling pathways and characterize specific immune phenotypes in patients. Emerging technologies such as machine learning can then be leveraged to identify druggable therapeutic targets and relate them to immune phenotypes and underlying infectious agents. This synergistic approach can lead to the development of new therapeutics and the identification of FDA approved drugs that can be repurposed for the treatment of sepsis.

A virtual synchronous generator (VSG) strategy can introduce the rotational inertia and damping characteristics of the synchronous generator to the static inverter, e.g., PV, wind generation, and ESS, which are used to enhance the system frequency support characteristics of the micro-grid. However, under various operations of the VSG, the inertia and damping support capabilities are different, and the conventional VSG strategy with a fixed control coefficient sacrifices a certain degree of dynamic regulation performance with less robustness. This research proposes an improved VSG strategy with adaptive inertia and damping coefficients to increase the flexibility of VSG. To this end, a mathematical model is first established to analyze the impact of various parameters on the characteristics of VSG, and then the root trajectory is used to explore the impacts of various rotational inertia and damping coefficients on the stability of the VSG system. Second, an improved control strategy with adaptive inertia and damping coefficients is proposed based on the characteristics of the second-order system and the system frequency deviations. Finally, a simulation system with the VSG is constructed based on MATLAB/Simulink. The effectiveness of the proposed control strategy is verified by comparing the simulation results to the conventional control strategy with the fixed control coefficients under over-frequency and under-frequency disturbances.

The prevalence of unsafe food poses a widespread challenge across numerous nations. Despite the continuous investments by the Chinese government in food safety regulation, the condition of food safety in China is still not ideal and requires substantial enhancements. Cost-effective, information-based strategies are essential for the effective management of food safety hazards. In this research, we established an extensive database of food enterprises with documented violations and carried out a randomized intervention trial to assess the effects of regulatory information interventions on the decrease of production violations in these enterprises. The findings reveal that interventions based on food safety regulatory information were instrumental in diminishing production violations among food enterprises and had spillover effects within a given geographic area. It is important to note that the impact of the intervention was delayed, with noticeable results on production violations becoming apparent 6 months post-intervention. Additionally, the degree of information communication and the degree of information concern can positively moderate the reduction of food enterprises’ production violation behavior by food safety regulatory information intervention.

S-palmitoylation is a reversible posttranslational modification, and the palmitoylation reaction in human-derived cells is mediated by the zDHHC family, which is composed of S-acyltransferase enzymes that possess the DHHC (Asp-His-His-Cys) structural domain. zDHHC proteins form an autoacylation intermediate, which then attaches the fatty acid to cysteine a residue in the target protein. zDHHC proteins sublocalize in different neuronal structures and exert dif-ferential effects on neurons. In humans, many zDHHC proteins are closely related to human neu-rological disor-ders. This review focuses on a variety of neurological disorders, such as AD (Alz-heimer’s disease), HD (Huntington’s disease), SCZ (schizophrenia), XLID (X-linked intellectual disability), attention deficit hyperactivity disorder and glioma. In this paper, we will discuss and summarize the research progress regarding the role of zDHHC proteins in these neu-rological disorders.

BackgroundCoronaVac has been authorized worldwide for preventing coronavirus disease 2019. Information on the safety, immunogenicity and consistency of different lots and workshops of CoronaVac is presented here.MethodsIn this randomized, double-blind, phase IV clinical trial in healthy children and adolescents aged 3-17 years, we aimed to assess the lot-to-lot and workshop-to-workshop consistency, as well as immunogenicity and safety of seven lots of commercial-scale CoronaVac from three workshops. Eligible participants were enrolled into three age cohorts (3-5, 6-11 and 12-17 years). Within each cohort, participants were randomly assigned to seven groups to receive two doses of CoronaVac, with four weeks apart. Serum samples were collected before the first dose and 28 days after the second dose for neutralizing antibody testing. The primary objective was to evaluate the consistency of immune response among different lots within workshop 2 or 3, as well as among different workshops. The primary endpoint was geometric mean titer (GMT) of neutralizing antibody at 28 days after full-course vaccination.ResultsBetween July 27th and November 19th, 2021, a total of 2,520 eligible participants were enrolled. Results showed that 95% confidence intervals (CIs) of GMT ratios for all comparative groups among different lots or workshops were within the equivalence criteria of [0.67, 1.5]. The GMT and seroconversion rate for all participants were 126.42 (95%CI: 121.82, 131.19) and 99.86% (95%CI: 99.59%, 99.97%) at 28 days after two-dose vaccination. The incidences of adverse reactions were similar among seven lots, and most adverse reactions were mild in Grade 1, with no serious adverse event.ConclusionCoronaVac is well-tolerated and can elicit a good immune response among children and adolescents. Lot-to-lot consistency results indicate stable manufacturing of commercial-scale CoronaVac.

Because of the crucial role of epidermal permeability barrier in regulation of cutaneous and extracutaneous functions, great efforts have been made to identify and develop the regimens that can improve epidermal permeability barrier function. Studies have demonstrated that oral administration of natural ingredients can improve epidermal permeability barrier in various skin conditions, including inflammatory dermatoses and UV-irradiation. Moreover, topical applications of some natural ingredients can also accelerate the repair of epidermal permeability barrier after acute barrier disruption and lower transepidermal water loss in the intact skin. Natural ingredient-induced improvements in epidermal permeability barrier function can be attributable to upregulation of keratinocyte differentiation, lipid production, antioxidant, hyaluronic acid production, expression of aquaporin 3 and sodium-hydrogen exchanger 1. In this review, we summarize the benefits of topical natural ingredients in epidermal permeability barrier in normal skin with or without acute barrier disruption and the underlying mechanisms.

BackgroundLysosomes are instrumental in intracellular degradation and recycling, with their functional alterations holding significance in tumor growth. Nevertheless, the precise role of lysosome-related genes (LRGs) in breast cancer (BC) remains elucidated. This study aimed to establish a prognostic model for BC based on LRGs.MethodsEmploying The Cancer Genome Atlas (TCGA) BC cohort as a training dataset, this study identified differentially expressed lysosome-related genes (DLRGs) through intersecting LRGs with differential expression genes (DEGs) between tumor and normal samples. A prognostic model of BC was subsequently developed using Cox regression analysis and validated within two Gene Expression Omnibus (GEO) external validation sets. Further analyses explored functional pathways, the immune microenvironment, immunotherapeutic responses, and sensitivity to chemotherapeutic drugs in different risk groups. Additionally, the mRNA and protein expression levels of genes within the risk model were examined by utilizing the Gene Expression Profiling Interactive Analysis (GEPIA) and Human Protein Atlas (HPA) databases. Clinical tissue specimens obtained from patients were gathered to validate the expression of the model genes via Real-Time Polymerase Chain Reaction (RT-PCR).ResultsWe developed a risk model of BC based on five specific genes (ATP6AP1, SLC7A5, EPDR1, SDC1, and PIGR). The model was validated for overall survival (OS) in two GEO validation sets (p=0.00034 for GSE20685 and p=0.0095 for GSE58812). In addition, the nomogram incorporating clinical factors showed better predictive performance. Compared to the low-risk group, the high-risk group had a higher level of certain immune cell infiltration, including regulatory T cells (Tregs) and type 2 T helper cells (Th2). The high-risk patients appeared to respond less well to general immunotherapy and chemotherapeutic drugs, according to the Tumor Immune Dysfunction and Exclusion (TIDE), Immunophenotype Score (IPS), and drug sensitivity scores. The RT-PCR results validated the expression trends of some prognostic-related genes in agreement with the previous differential expression analysis.ConclusionOur innovative lysosome-associated signature can predict the prognosis for BC patients, offering insights for guiding subsequent immunotherapeutic and chemotherapeutic interventions. Furthermore, it has the potential to provide a scientific foundation for identifying prospective therapeutic targets.

A previous metabolomic and genome-wide association analysis of maize screened a glucose-6-phosphate 1-epimerase (ZmG6PE) gene, which responds to low-phosphorus (LP) stress and regulates yield in maize’s recombinant inbred lines (RILs). However, the relationship of ZmG6PE with phosphorus and yield remained elusive. This study aimed to elucidate the underlying response mechanism of the ZmG6PE gene to LP stress and its consequential impact on maize yield. The analysis indicated that ZmG6PE required the Aldose_epim conserved domain to maintain enzyme activity and localized in the nucleus and cell membrane. The zmg6pe mutants showed decreased biomass and sugar contents but had increased starch content in leaves under LP stress conditions. Combined transcriptome and metabolome analysis showed that LP stress activated plant immune regulation in response to the LP stress through carbon metabolism, amino acid metabolism, and fatty acid metabolism. Notably, LP stress significantly reduced the synthesis of glucose-1-phosphate, mannose-6-phosphate, and β-alanine-related metabolites and changed the expression of related genes. ZmG6PE regulates LP stress by mediating the expression of ZmSPX6 and ZmPHT1.13. Overall, this study revealed that ZmG6PE affected the number of grains per ear, ear thickness, and ear weight under LP stress, indicating that ZmG6PE participates in the phosphate signaling pathway and affects maize yield-related traits through balancing carbohydrates homeostasis.

Single-cell manipulation is the key foundation of life exploration at individual cell resolution. Constructing easy-to-use, high-throughput, and biomimetic manipulative tools for efficient single-cell operation is quite necessary. In this study, a facile and efficient encapsulation of single cells relying on the massive and controllable production of droplets and collagen–alginate microgels using a microfluidic device is presented. High monodispersity and geometric homogeneity of both droplet and microgel generation were experimentally demonstrated based on the well-investigated microfluidic fabricating procedure. The reliability of the microfluidic platform for controllable, high-throughput, and improved single-cell encapsulation in monodisperse droplets and microgels was also confirmed. A single-cell encapsulation rate of up to 33.6% was achieved based on the established microfluidic operation. The introduction of stromal material in droplets/microgels for encapsulation provided single cells an in vivo simulated microenvironment. The single-cell operation achievement offers a methodological approach for developing simple and miniaturized devices to perform single-cell manipulation and analysis in a high-throughput and microenvironment-biomimetic manner. We believe that it holds great potential for applications in precision medicine, cell microengineering, drug discovery, and biosensing.

Objective: While several drugs have been linked to acute pancreatitis (AP), the AP-related risk of most drugs remains unclear. This study investigated the risk factors for drug-induced AP by analyzing a large dataset from the FDA Adverse Event Reporting System (FAERS).Methods: The reporting odds ratios (ROR) were used to assess the reports of drug-induced AP from the first quarter of 2004 to the second quarter of 2022. Single-factor, LASSO, and multi-factor regression analysis were performed to explore drug-related AP-related risk factors. Bonferroni correction was applied for the multiple comparisons performed.Results: A total of 264 drugs associated with AP, including antineoplastic drugs (35/264), antidiabetic drugs (28/264), antibacterial drugs (24/264), immunomodulatory drugs (11/264), antipsychotic drugs (6/264), and other drugs (160/264) were retrieved. Multi-factor analysis showed that males, age 41–54 years old, and 36 drugs, including Tigecycline, were risk factors for drug-related AP. The median time to drug-related AP onset was 31 days (interquartile range [IQR] 7–102 days) and about 75% of adverse events occurred within 100 days.Conclusion: These findings may help clinicians to identify drug-related AP at the early stage and can be used to inform future studies of drug-related AP pathogenesis.