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Abstract Background Investigating the trend of changes in the occurrence of necrotizing enterocolitis (NEC) in preterm infants during 9 years and analyzing the risk factors of NEC with the purpose of providing reference for clinical diagnosis and treatment of NEC. Methods Clinical data of NEC in preterm infants with Bell’s stage ≥ II from January 2013 to December 2021 in the Neonatology Department of the Third Affiliated Hospital of Zunyi Medical University was retrospectively analyzed. Trends in the occurrence of NEC in preterm infants were analyzed by the trend chi-square test. Subsequently, the general data (sex, gestational age, singleton or multiple births, birth weight, serum albumin, alkaline phosphatase, sepsis, blood transfusion, mechanical ventilation, RDS, arterial catheterization) and perinatal data (intrauterine distress, turbid amniotic fluid, premature rupture of membranes, mode of delivery, fetal heart abnormalities, diabetes mellitus) were collected; then, the risk factors for NEC were analyzed by univariate and multivariate logistic-regression analysis. Results In the past 9 years, 77 cases of NEC occurred, with the incidence rate of 1.95%, and the incidence of NEC in preterm infants has been increasing year by year (P

Abstract Background The aim of this study was to evaluate the psychological distress pre-operatively, at 3, 6, and 12 months in patients who underwent lumbar spine fusion surgery. Methods A total of 440 patients received instrumented lumbar spine fusion were enrolled. Psychological distress was evaluated using the Modified Somatic Perception Questionnaire (MSPQ) and the Modified Zung Depressive Index (ZDI). The results of lumbar fusion surgery were evaluated using the Oswestry Disability Index (ODI), the Japanese Orthopedic Association (JOA-29), and the visual analog scale (VAS). Results Psychological distress was reported among 23% of patients and 7, 5.5, and 4.0% of the patients preoperatively, at 3, 6, and 12 months after lumbar surgery, respectively. The mean MSPQ score decreased from 8.78 (before surgery) to 4.30, 3.52, and 3.43 at 3, 6 and 12 months in after surgery, respectively, in patients with psychological distress patients (p

Summary: The “innate-like” T cell compartment, known as Tinn, represents a diverse group of T cells that straddle the boundary between innate and adaptive immunity. We explore the transcriptional landscape of Tinn compared to conventional T cells (Tconv) in the human thymus and blood using single-cell RNA sequencing (scRNA-seq) and flow cytometry. In human blood, the majority of Tinn cells share an effector program driven by specific transcription factors, distinct from those governing Tconv cells. Conversely, only a fraction of thymic Tinn cells displays an effector phenotype, while others share transcriptional features with developing Tconv cells, indicating potential divergent developmental pathways. Unlike the mouse, human Tinn cells do not differentiate into multiple effector subsets but develop a mixed type 1/type 17 effector potential. Cross-species analysis uncovers species-specific distinctions, including the absence of type 2 Tinn cells in humans, which implies distinct immune regulatory mechanisms across species.

Introduction: Anti-programmed cell death 1 (PD-1) immunotherapy is the standard of care for metastatic NSCLC but many tumors develop resistance. We hypothesized that combining a T-cell agonist such as varlilumab (anti-CD27 antibody) with checkpoint inhibition may be synergistic and this synergy may be potentiated further by using targeted radiation (RT). Methods: We conducted an open-label, single-center, phase I trial (NCT04081688) to determine the safety and clinical benefit of the atezolizumab and varlilumab in combination with palliative RT in patients with advanced or metastatic NSCLC with progression on prior programmed cell death ligand 1therapy. On day 1 of each 21-day cycle, patients received varlilumab followed by atezolizumab on day 2. RT to a lung lesion was administered between cycle 1 and cycle 2. Results: A total of 15 patients were enrolled (one patient did not start treatment). The median age was 64 years; 10 patients were female. Eight patients (57%) had at least one treatment-related adverse event (AE) and 7 (50%) had at least one grade III or worse treatment-related AE. There was only one grade III immune-related AE requiring steroids (1 diarrhea and colitis); there were no treatment-related deaths. Of the 12 patients evaluable for efficacy, three patients had stable disease (2 with stable disease > 4 mo) and the clinical benefit rate was 25%. The median progression-free survival was two months and the median overall survival was 6.4 months. Conclusions: Varlilumab in combination with atezolizumab and RT was safe and well tolerated; no additional signal was identified for toxicity. Clinical activity for the combination was modest with 25% of patients with stable disease as the best response.

Obesity, characterized by its complexity and heterogeneity, has emerged as a significant public health concern. Its association with increased incidence and mortality of cardiovascular diseases stems not only from its complications and comorbidities but also from the endocrine effects of adipose tissue. Abdominal aortic aneurysm (AAA), a chronic inflammatory condition, has been closely linked to obesity. Intriguingly, mild obesity appears to confer a protective effect against AAA mortality, whereas severe obesity and being underweight do not, giving rise to the concept of the “obesity paradox”. This review aims to provide an overview of obesity and its paradoxical relationship with AAA, elucidate its underlying mechanisms, and discuss the importance of preoperative weight loss in severely obese patients with AAA.

BackgroundYoung adults engage in behaviors that place them at risk for skin cancer. Dissemination of digital health promotion interventions via social media is a potentially promising strategy to modify skin cancer risk behaviors by increasing UV radiation (UVR) protection and skin cancer examinations. ObjectiveThis study aimed to compare 3 digital interventions designed to modify UVR exposure, sun protection, and skin cancer detection behaviors among young adults at moderate to high risk of skin cancer. MethodsThis study was a hybrid type II effectiveness-implementation randomized controlled trial of 2 active interventions, a digital skin cancer risk reduction intervention (UV4.me [basic]) compared with an enhanced version (UV4.me2 [enhanced]), and an electronic pamphlet (e-pamphlet). Intervention effects were assessed over the course of a year among 1369 US young adults recruited primarily via Facebook and Instagram. Enhancements to encourage intervention engagement and behavior change included more comprehensive goal-setting activities, ongoing proactive messaging related to previously established mediators (eg, self-efficacy) of UVR exposure and protection, embedded incentives for module completion, and ongoing news and video updates. Primary outcome effects assessed via linear regression were UVR exposure and sun protection and protection habits. Secondary outcome effects assessed via logistic regression were skin self-exams, physician skin exams, sunscreen use, indoor tanning, and sunburn. ResultsThe active interventions increased sun protection (basic: P=.02; enhanced: P

Cognitive impairment is a decline in people’s ability to think, learn, and remember, and so forth. Cognitive impairment is a global health challenge that affects the quality of life of thousands of people. The condition covers a wide range from mild cognitive impairment to severe dementia, which includes Alzheimer’s disease (AD) and Parkinson’s disease (PD), among others. While the etiology of cognitive impairment is diverse, the role of chemokines is increasingly evident, especially in the presence of chronic inflammation and neuroinflammation. Although inflammatory chemokines have been linked to cognitive impairment, cognitive impairment is usually multifactorial. Researchers are exploring the role of chemokines and other inflammatory mediators in cognitive dysfunction and trying to develop therapeutic strategies to mitigate their effects. The pathogenesis of cognitive disorders is very complex, their underlying causative mechanisms have not been clarified, and their treatment is always one of the challenges in the field of medicine. Therefore, exploring its pathogenesis and treatment has important socioeconomic value. Chemokines are a growing family of structurally and functionally related small (8–10 kDa) proteins, and there is growing evidence that pro-inflammatory chemokines are associated with many neurobiological processes that may be relevant to neurological disorders beyond their classical chemotactic function and play a crucial role in the pathogenesis and progression of cognitive disorders. In this paper, we review the roles and regulatory mechanisms of pro-inflammatory chemokines (CCL2, CCL3, CCL4, CCL5, CCL11, CCL20, and CXCL8) in cognitive impairment. We also discuss the intrinsic relationship between the two, hoping to provide some valuable references for the treatment of cognitive impairment.

Abstract Background Teriparatide (TPTD) is a widely used anabolic agent for the treatment of osteoporosis. Several factors have been identified to be related to bone mineral density (BMD) increase in anti-osteoporosis treatment with other agents; however, there has been no systematic analysis to summarize the associated determinants of BMD reaction to daily teriparatide treatment. Methods In this retrospective study, we performed a comprehensive investigation involving not only clinical data but also several relevant lifestyle factors to be examined for their potential contribution to BMD response. This post-hoc analysis included 258 post-menopaused patients with osteoporosis who received TPTD at 20 µg/day for 12 months. Univariate and multivariate analyses were conducted to distinguish the response variables of lumbar spine (LS) BMD transformation, the principal outcome measure of efficacy, from the baseline at 12 months. Results Twelve months of TPTD treatment resulted in an absolute 0.39 ± 0.37 increase in T-score of LS BMD. Gastrointestinal disease, prior bisphosphonate or glucocorticoid treatment, no vitamin K2 supplementation, low levels of serum 25(OH)D and PINP, weak increment of PINP and β-CTX at 3 months, unhealthy lifestyle (excessive smoking, tea, coffee, and drinking), vegetarian diet pattern, low ALT level, and high BMD at baseline were determined by univariate analyses to be related to the weak reaction of TPTD treatment (P

Abstract Background Targeting receptor-interacting serine/threonine protein kinase 1 could mitigate the devastating sequelae of the hyperinflammatory state observed in severe cases of COVID-19. This study explored the immunomodulatory and clinical effects of the receptor-interacting serine/threonine protein kinase 1 inhibitor SAR443122 (eclitasertib) in patients with severe COVID-19. Methods In this Phase 1b, double-blinded, placebo-controlled study (NCT04469621) a total of 82 patients were screened, of whom 68 patients were eligible and randomized (2:1) to receive eclitasertib 600 mg (300 mg twice daily) or placebo up to 14 days. Primary outcome was relative change in C-reactive protein from baseline to Day 7. Time to clinical improvement using 7-point ordinal scale, ventilator/respiratory failure-free days, change in SpO2/FiO2 ratio, and biomarkers of severe COVID-19 were explored. Results Geometric mean ratio (point estimate [90% confidence interval]) of the relative change from baseline in C-reactive protein with eclitasertib vs. placebo on Day 7 was 0.85 (0.49–1.45; p = 0.30). Median time to 50% decrease in C-reactive protein from baseline was 3 days vs. 5 days (p = 0.056) with eclitasertib vs. placebo. Median time to ≥ 2-point improvement on 7-point clinical symptoms scale was 8 days vs. 10 days with eclitasertib vs. placebo (p = 0.38). Mean ventilator/respiratory failure-free days, change in baseline-adjusted SpO2/FiO2 ratio, and clinical biomarkers showed consistent numerical improvements with eclitasertib vs. placebo. The most frequently reported treatment-emergent adverse events were gastrointestinal disorders and condition aggravated/worsened COVID-19 pneumonia. Conclusions Eclitasertib was well tolerated with consistent trends toward more rapid resolution of inflammatory biomarkers and clinical improvement in severe COVID-19 patients than placebo. ClinicalTrials.gov identifier NCT04469621, first posted on clinicaltrials.gov on July 14, 2020.

Abstract The capacity to identify small amounts of pathogens in real samples is extremely useful. Herein, we proposed a sensitive platform for detecting pathogens using cyclic DNA nanostructure@AuNP tags (CDNA) and a cascade primer exchange reaction (cPER). This platform employs wheat germ agglutinin-modified Fe3O4@Au magnetic nanoparticles (WMRs) to bind the E. coli O157:H7, and then triggers the cPER to generate branched DNA products for CDNA tag hybridization with high stability and amplified SERS signals. It can identify target pathogens as low as 1.91 CFU/mL and discriminate E. coli O157:H7 in complex samples such as water, milk, and serum, demonstrating comparable or greater sensitivity and accuracy than traditional qPCR. Moreover, the developed platform can detect low levels of E. coli O157:H7 in mouse serum, allowing the discrimination of mice with early-stage infection. Thus, this platform holds promise for food analysis and early infection diagnosis.

Abstract Wireless and battery-free radio-frequency (RF) sensors can be used to create physical spaces that ambiently sense and respond to human activities. Making such sensors ultra-flexible and transparent is important to preserve the aesthetics of living environments, accommodate daily activities, and functionally integrate with objects. However, existing RF sensors are unable to simultaneously achieve high transparency, flexibility, and the electrical conductivity required for remote room-scale operation. Here, we report 4.5 µm RF tag sensors achieving transparency exceeding 90% that provide capabilities in room-scale ambient wireless sensing. We develop a laser-assisted water-based adhesion-reversion process to digitally realize computer-aided RF design at scale. By individually tagging multiple objects and regions of the human body, we demonstrate multiplexed wireless tracking of human-environment interactions and physiological signals at a range of up to 8 m. These radio-frequency identification sensors open opportunities for non-intrusive wireless sensing of daily living spaces for applications in health monitoring and elderly care.

Abstract Total neointima implantation (patch neointima technique + triple‐branched stent graft placement) has been performed in proximal aortic repair for acute type A aortic dissection (ATAAD) for more than 10 years at a center. However, there is no report on the mid‐term outcomes with a control group of the surgical procedure. Consequently, the authors aimed to evaluate the safety and efficacy of this technique in this study. Patients who underwent the total neointima implantation were classified as Group A, and those who underwent the conventional aortic root reconstruction with the “sandwich” technique and the total aortic arch replacement were classified as Group B. Furthermore, the authors described the preoperative characteristics, operative data, and patient outcomes. Group A patients experienced a shorter surgery duration, lower volumes of perioperative bleeding, and fewer red blood cell transfusions. The incidence of neurological complications was significantly reduced in Group A. All patients maintained a normal range of proximal aortic sizes after surgery. Kaplan–Meier analysis revealed no significant differences between the patients in the two groups regarding cumulative mortality and the incidence of moderate‐to‐severe aortic insufficiency. In well‐selected patients, total neointima implantation is an alternative procedure for the surgical repair of ATAAD.

Background: Pneumococcus serotyping is important for monitoring serotype epidemiology, vaccine-induced serotypes replacement and emerging pathogenic serotypes. However, the lack of high-resolution serotyping tools has hindered its widespread implementation. Methods: We devised a single-step, multiplex real-time polymerase chain reaction (PCR)-based MeltArray approach termed PneumoSero that can identify 92 serotypes with individual recognition of 54 serotypes, including all 24 currently available vaccine types. The limit of detection (LOD) and the ability to coexisting serotypes were studied, followed by analytical evaluation using 92 reference pneumococcal strains and 125 non-pneumococcal strains, and clinical evaluation using 471 pneumococcus isolates and 46 pneumococcus-positive clinical samples. Results: The LODs varied with serotypes from 50 to 100 copies per reaction and 10 % of the minor serotypes were detectable in samples containing two mixed serotypes. Analytical evaluation presented 100 % accuracy in both 92 reference pneumococcal strains and 125 non-pneumococcal strains. Clinical evaluation of 471 pneumococcus isolates displayed full concordance with Sanger sequencing results. The 46 clinical specimens yielded 45 typeable results and one untypeable result. Of the 45 typeable samples, 41 were of a single serotype and four were of mixed serotypes, all of which were confirmed by Sanger sequencing or separate PCR assays. Conclusion: We conclude that the PneumoSero assay can be implemented as a routine tool for pneumococcal serotyping in standard microbiology laboratories and even in clinical settings.

Cyprinus carpio var. Quanzhounensis, native to Quanzhou County, Guilin City, Guangxi, has a dark brown body color, translucent gill cover, and abdominal skin, and is an important farmed species in the local integrated rice-fishery industry. A comparative study on the skin of Cyprinus carpio var. Quanzhounensis revealed a lack of reflective guanine crystals on the body surface and a significantly higher melanin content than that of C. carpio var. Jian, which was tentatively considered the direct cause of variations in body color of this group. Iridocytes are a pigment cell species that contain regularly arranged guanine crystals, which are the key material basis for the metallic luster of the fish body surface. In species such as medaka (Oryzias latipes) and zebrafish (Danio rerio), the absence of guanine crystals is considered a manifestation of the absence of iridocyte differentiation and therefore is ideal for studying the mechanism of pigment cell differentiation. The pnp4a, Gbx2, sox10, tfec genes and other iridocyte-related genes have been mined using mutant materials, and we have uncovered the differentiation mechanism that regulates the formation of iridescent cells. C. carpio var. color has abundant genetic variation in body color and is a good material for studying the mechanism of body color determination in fish. The roles of ASIP and MC1R in the aggregation and distribution of melanin and formation of black spots in C. carpio var. color were verified. The guanine crystalline deletion trait of C. carpio var. Quanzhounensis may be loaded with regulatory mechanism diversity and mutation loci related to guanine crystal formation or iridescent cell differentiation. In addition, as a rice-fish culture species, the living environment of C. carpio var. Quanzhounensis harvestmen differ significantly from pond and net-pen culture species, requiring high resistance to disease, adversity, and transport. It is unclear whether the absence of guanine crystals in their skin leads to changes in their basal physiological state, and in-depth studies are beneficial for accurate assessment of culture performance. To reveal the structural basis and transcriptomic characteristics of guanine crystalline deficiency traits in the skin of C. carpio var. Quanzhounensis in this study, we selected the subscale tissues with the most significant differences in guanine crystalline distribution as the control material, and transmission electron microscopy was used to observe the tissue structure and full-length transcriptome sequencing to understand the structural and transcriptomic characteristics of guanine crystalline deficiency in the skin of C. carpio var. Quanzhounensis. The results of this study provide information for the analysis of body color traits, identification of economic traits, and utilization of germplasm resources. Transmission electron microscopy of the subscale tissue sections revealed two significant differences in the histological structure of C. carpio var. Quanzhounensis, and C. carpio var. Jian. First, guanine crystals were absent in C. carpio var. Quanzhounensis, whereas guanine crystals were widely present in the tissues of C. carpio var. Jian and cascading cavities were observed in the sections after guanine crystals were dislodged. Second, the number and density of melanin particles in the tissues of C. carpio var. Quanzhounensis harvestmen were significantly higher than those of C. carpio var. Jian, showing smaller, darker, and more numerous particles, which is consistent with the darker color and lack of silvery reflective material on the body surface of C. carpio var. Quanzhounensis harvestmen. The transcriptome characteristics were analyzed using Oxford Nanopore (ONT) sequencing technology, and 2.88~3.26 Gb of high-quality data were obtained for each sample. The number of full-length sequences after filtering ribosomal RNA for all sample data was 2 203 826~2 412 500, and the proportion of full-length sequences for each sample was 87.06%~88.57%. The comparison rate was 90.35%~92.46%. Variable splicing events in the transcripts were counted; 3 075 variable splicing events and 57 624 variable polyadenylation events were detected; and 15 615 new coding region sequences and 771 long-stranded non-coding RNAs were predicted. The number of exon jumps and intron retention in variable splicing events differed significantly (P

This study delves deeply into the traffic light intersection control issue for connected autonomous vehicles (CAVs). First, we employed the vehicle dynamics simulation software, CarSim, to model the vehicle and utilized the intelligent driving simulation software, PreScan, to establish a road environment model. Subsequently, we designed a rule-based traffic light crossing controller (RB-TLCC) for CAVs in MATLAB/Simulink and implemented a co-simulation using CarSim and PreScan. Furthermore, we conducted driver-in-the-loop studies using the Logitech G27 driving simulator kit and compared the experimental results with those from the RB-TLCC. Our findings indicate that RB-TLCC enhances the regenerative braking energy by 23.5%, improves traffic efficiency by 17.9%, and increases driving smoothness by 50.7%. Additionally, based on Markov Chain theory, we proposed a multi-objective optimization model (MO-OM) for CAVs traffic light intersection crossing using the Proximal Policy Optimization algorithm (PPO). A comparison was conducted under two different operating conditions between RB-TLCC and dynamic programming algorithms (DP). The results indicated that the MO-OM proposed in this study exhibited the best comprehensive control performance among the three control methods. While adhering to traffic regulations, it enhances the recuperation of braking energy, efficiency of vehicle passage, and smoothness of travel at traffic light intersections. This study offers effective methodologies for enhancing the performance of CAVs in traffic light intersection control and holds significant reference value for the advancement of future intelligent transportation systems (ITS).

Highlights Nanocomposite/hydrogel hybrid electrodes are created with high interfacial toughness by introducing soft microfoams as the mechanically interlocking layer. In the hybrid electrodes, silver nanowires and hydrogels are electrically connected through the porous microfoams, achieving high conductivity and low contact impedance for high-quality biopotential recordings. The microfoam-enabled bonding strategy is generally applicable to diverse polymer substrates.

Summary: Background: The HVTN 705 Imbokodo trial of 2636 people without HIV and assigned female sex at birth, conducted in southern Africa, evaluated a heterologous HIV-1 vaccine regimen: mosaic adenovirus 26-based vaccine (Ad26.Mos4.HIV) at Months 0, 3, 6, 12 and alum-adjuvanted clade C gp140 at Months 6, 12. Per-protocol vaccine efficacy (VE) against HIV-1 diagnosis from seven to 24 months was 14.1% (95% CI: −22.0% to 39.5%). Immune correlates analysis was performed for markers selected based on prior evidence in efficacy trials and/or nonhuman primate models. Methods: Humoral and cellular immune response markers at Month 7 were evaluated as immune correlates of risk and of protection in a breakthrough case–control cohort (n = 52 cases, 246 non-cases). Primary markers were IgG binding to vaccine-strain gp140, IgG3 binding to diverse Env antigens (IgG3 Env breadth), IgG3 binding to diverse V1V2 antigens (IgG3 V1V2 breadth), antibody-dependent phagocytosis against the vaccine-strain gp140, Env-specific CD4+ and CD8+ T-cell responses, and multi-epitope functions. Findings: No immune markers were statistically significant correlates of risk. IgG3 V1V2 breadth trended toward an inverse association: hazard ratio 0.70 (95% CI: 0.36 to 1.35; p = 0.29) per 10-fold increase and 0.51 (95% CI: 0.21 to 1.24; p = 0.14) in a Cox model with all primary markers. The VE estimate was 11.8% (95% CI: −17.9% to 34.0%) at all IgG3 V1V2 breadth values below 667 weighted geometric mean net MFI; just above this value, the VE estimate sharply increased to 62.6% (95% CI: −17.9% to 89.6%), and further increased to 80.9% (95% CI: −17.9% to 99.5%) at 1471 MFI, the 95th percentile of the marker distribution. Mediation analysis yielded a VE of 35.7% (95% CI: 15.0% to 51.3%) attributable to the vaccine's impact on this marker. Interpretation: The trend in association of greater IgG3 V1V2 antibody breadth with lower likelihood of HIV acquisition is consistent with the identification of antibodies against V1V2 as immune correlates in three other HIV vaccine efficacy trials and suggests that a greater emphasis should be placed on studying this region in the HIV-1 envelope as a vaccine immunogen. Funding: National Institute of Allergy and Infectious Diseases and Janssen Vaccines & Prevention BV.

IntroductionBorderline Personality Disorder (BPD) traits play a crucial role in the prognosis of psychiatric disorders, as well as in assessing risks associated with negativity and impulsivity. However, there is a lack of data regarding the distribution characteristics of BPD traits and symptoms within clinical populations.MethodsA total of 3015 participants (1321 males, 1694 females) were consecutively sampled from outpatients at the psychiatric and psycho-counseling clinics at the Shanghai Mental Health Center. BPD symptoms were assessed using a self-reported personality diagnostic questionnaire. Having BPD traits is defined as having five or more positive items in self-reported BPD characteristics. Participants were stratified into male and female groups, age groups, and diagnostic groups (schizophrenia, mood disorders, anxiety disorders). Exploratory factor analysis using principal components analysis was conducted. Three factors were identified: “F1: Affective Instability and Impulsivity”, “F2: Interpersonal Unstable and Extreme Reactions”, and “F3: Identity Disturbance”.ResultsAmong 3015 participants, 45.9% of the patients self-reported BPD traits. Comparing of male and female patients, there was no statistically significant difference in the occurrence rate of BPD traits (χ2 = 1.835, p=0.176). However, in terms of symptoms, female patients reported more symptoms than male patients. Female patients also exhibited more pronounced features on F2 compared to male patients (t =-1.972, p=0.049). There is a general decrease in BPD traits, symptoms, and factors with increasing age. Specifically, the proportion of positive BPD traits is approximately halved before the age of 30 and decreases to around one-third after the age of 30. BPD traits were most common in the Mood Disorders group at 55.7%, followed by the Anxiety Disorders group at 44.4%, and Schizophrenia group at 41.5% (χ2 = 38.084, p

Esophageal squamous cell carcinoma (ESCC), the most common pathological type of esophageal cancer, is one of the leading causes of cancer death worldwide, but an effective therapeutic avenue is still absent. This study was to evaluate the therapeutic effect of Agaricus blazei Murrill polysaccharides (ABP) and Enteromorpha prolifera polysaccharides (EP) on ESCC. The results showed that both ABP and EP have therapeutic effects on multiple malignant processes of ESCC, such as proliferation, migration, invasion, and apoptosis, in vitro. Moreover, both ABP and EP retard tumor growth in vivo and the growth of ESCC-derived organoids. A series of genes and proteins changed upon treatments with ABP and EP after RNA sequencing and proteomics analysis. Autophagy, mitophagy and ferroptosis were enriched after treatments with these two polysaccharides, suggesting that the consumption of ABP and EP may represent a promising dietary supplement for ESCC therapy.

To assess the optimal dietary protein requirement of adult red swamp crayfish (Procambarus clarkii) farming in the rice field, six isoenergetic and isolipid diets were formulated to contain graded levels of 28%, 31%, 34%, 37%, 40% and 43% crude protein (called Diet 28–43 group). Each diet was assigned to a triplicate of 20 experimental crayfish with the average initial body weight of (15.17 ± 0.23) g for 42 days. Our results showed that the final body weight, weight gain rate and specific growth rate of red swamp crayfish adult in the Diet 34, Diet 37, Diet 40 and Diet 43 groups were significantly higher than those of other groups (P 0.05). Activities of trypsin and lipase in the intestine were significantly affected by dietary protein levels (P 0.05). Moreover, higher dietary protein significantly increased the antioxidant and non-specific immunity enzyme activity. Broken-line regression analysis based on weight gain rate and specific growth rate showed that the optimal dietary protein level for maximum growth performance of crayfish was 32.68%. According to the present study on the growth performance, the muscle of Diet 28 group (SM) and Diet 34 group (LM) individuals were selected for transcriptome sequencing. The results showed that there were 444 differential genes in SM and LM, of which 282 genes were up-regulated and 162 genes were down-regulated. DEGs of SM and LM groups differential genes were mainly enriched in citrate cycle, pyruvate cycle, glycolysis/gluconeogenesis, etc. Beyond that, transcriptomic results also hinted that glycolysis/gluconeogenesis and citrate cycle signaling pathways might be its growth change mechanisms. In addition, the aldo, eno, pk, pdhb, adh, sdha, fh, mdh2, cs were also identified as the key factors involved in glycolysis/gluconeogenesis and citrate cycle pathways. In conclusion, combining growth performance and transcriptome data, we recommended that diets with 32.68%− 34.00% protein were optimal for red swamp crayfish in the rice-shrimp farming pattern.

Polycystic ovary syndrome (PCOS) is a common systemic disorder related to endocrine disorders, affecting the fertility of women of childbearing age. It is associated with glucose and lipid metabolism disorders, altered gut microbiota, and insulin resistance. Modern treatments like pioglitazone, metformin, and spironolactone target specific symptoms of PCOS, while in Chinese medicine, moxibustion is a common treatment. This study explores moxibustion’s impact on PCOS by establishing a dehydroepiandrosterone (DHEA)-induced PCOS rat model. Thirty-six specific pathogen-free female Sprague-Dawley rats were divided into four groups: a normal control group (CTRL), a PCOS model group (PCOS), a moxibustion treatment group (MBT), and a metformin treatment group (MET). The MBT rats received moxibustion, and the MET rats underwent metformin gavage for two weeks. We evaluated ovarian tissue changes, serum testosterone, fasting blood glucose (FBG), and fasting insulin levels. Additionally, we calculated the insulin sensitivity index (ISI) and the homeostasis model assessment of insulin resistance index (HOMA-IR). We used 16S rDNA sequencing for assessing the gut microbiota, 1H NMR spectroscopy for evaluating metabolic changes, and Spearman correlation analysis for investigating the associations between metabolites and gut microbiota composition. The results indicate that moxibustion therapy significantly ameliorated ovarian dysfunction and insulin resistance in DHEA-induced PCOS rats. We observed marked differences in the composition of gut microbiota and the spectrum of fecal metabolic products between CTRL and PCOS rats. Intriguingly, following moxibustion intervention, these differences were largely diminished, demonstrating the regulatory effect of moxibustion on gut microbiota. Specifically, moxibustion altered the gut microbiota by increasing the abundance of UCG-005 and Turicibacter, as well as decreasing the abundance of Desulfovibrio. Concurrently, we also noted that moxibustion promoted an increase in levels of short-chain fatty acids (including acetate, propionate, and butyrate) associated with the gut microbiota of PCOS rats, further emphasizing its positive impact on gut microbes. Additionally, moxibustion also exhibited effects in lowering FBG, testosterone, and fasting insulin levels, which are key biochemical indicators associated with PCOS and insulin resistance. Therefore, these findings suggest that moxibustion could alleviate DHEA-induced PCOS by regulating metabolic levels, restoring balance in gut microbiota, and modulating interactions between gut microbiota and host metabolites.

Abstract Emerging evidence indicates that SOX2 is an oncogene for esophageal squamous cell carcinoma (ESCC). However, direct targeting of SOX2 is not feasible given that this transcription factor plays important roles in the maintenance of tissues such as the brain. Here, we identified CDP (Homeobox protein cut-like 1 or CASP) as a unique SOX2 binding partner enriched in ESCC with Duolink proximity ligation assay, bimolecular fluorescence complementation (BiFc) and immunoprecipitation. We then screened a peptide aptamer library using BiFc and immunoprecipitation and identified several peptide aptamers, including P58, that blocked the CDP/SOX2 interaction, leading to the inhibition of ESCC progress in vitro and in vivo. Upon administration, synthetic peptide P58, containing the YGRKKRRQRRR cell-penetrating peptide and the fluorophore TAMRA, also blocked the growth and metastasis of ESCC in both mice and zebrafish. Therefore, targeting the SOX2 binding partner CDP with peptide P58 offers an alternative avenue to treat ESCC with increased SOX2 levels.

Abstract Background Giant cell arteritis (GCA) is primarily treated with glucocorticoids (GCs), which have substantial toxicity. Tocilizumab, an interleukin-6-receptor inhibitor (IL-6Ri), showed beneficial effects in GCA, leading to its approval. This study investigated the efficacy and safety of sarilumab (another IL-6Ri) in GCA. Methods This Phase 3, double-blind study comprised a 52-week treatment period and a 24-week follow-up phase. Eligible GCA patients were randomized to receive sarilumab 200 mg (SAR200 + 26W) or 150 mg (SAR150 + 26W) with a 26-week GC taper, or placebo with a 52-week (PBO + 52W) or 26-week (PBO + 26W) GC taper. The primary efficacy endpoint was sustained remission (SR) at week 52. Additional endpoints were SR at week 24, cumulative GC dose, and safety. The study was discontinued prematurely due to protracted recruitment timelines, because of the impact of COVID-19. Therefore, only descriptive statistics were summarized. Results Of the planned 360 subjects, only 83 were randomized and 36 were included in the week 52 analysis. At week 52, 46% (n = 6/13) of patients in SAR200 + 26W, 43% (n = 3/7) in SAR150 + 26W, 30% (n = 3/10) in PBO + 52W, and 0 (n = 0/6) in PBO + 26W taper groups achieved SR. Sensitivity analyses, excluding acute-phase reactants from the SR definition, showed similar results for SAR groups, but 60% (n = 6/10) in PBO + 52W and 17% (n = 1/6) in PBO + 26W taper groups achieved SR at week 52. Similar findings were noted at week 24. The proportions of patients who adhered to GC taper from week 12 through week 52 in each group were as follows: 46% (n = 6/13, SAR200 + 26W), 43% (n = 3/7, SAR150 + 26W), 60% (n = 6/10, PBO + 52W), and 33% (n = 2/6, PBO + 26W). The median actual cumulative GC dose received in the SAR200 + 26W group was lower than other groups. Most patients (80–100%) experienced treatment-emergent adverse events, with similar incidences reported across groups. Conclusions Owing to the small sample size due to the early termination, it is difficult to draw clear conclusions from this study. There were no unexpected safety findings. Trial registration ClinicalTrials.gov NCT03600805. Registered on July 26, 2018.

A 9-week feeding trial was performed to investigate the effects of substituting fish meal (FM) with defatted mealworm Tenebrio molitor meal (TM) on the growth, body composition, serum immune index, as well as histology, barrier functions, digestive enzymatic activities, and microbial communities of the intestine of spotted seabass (Lateolabrax maculatus). In this study, the basal diet was formulated to contain 30% FM, and five experimental diets were formulated by replacing FM with TM at different levels: 0 (TM 0), 5% (5% TM), 10% (10% TM), 15% (15% TM), and 20% (20% TM). Juvenile spotted seabass (2.83±0.02) g were randomly assigned to five treatments with three replicates and 20 fish per replicate. The results showed that the weight gain rate, specific growth rate, and protein productive value of spotted seabass first increased and then decreased with an increase in TM. Among the treatments, there were no difference in the feed efficiency, feeding rate, survival, hepatosomatic index, abdominal fat ratio, or body composition (P > 0.05), but the viscerosomatic index was higher in the 5% TM treatment than that in the 20% TM treatment (P < 0.05). The serum lysozyme activity was induced in the 5% TM treatment compared to that in other TM treatments (P > 0.05). Intestinal histomorphology of spotted seabass was altered with increased dietary TM levels. Compared with the FM treatment, the intestinal villus width, villus height, and muscular thickness were increased significantly in the 5% TM treatment, while all three indices were decreased significantly in the 20% TM treatment (P < 0.05). Meanwhile, the expression of the pro-inflammatory gene IL-1β was significantly down-regulated in 5%–15% TM treatments compared to that in the FM and 20% TM treatments (P < 0.05). A similar pattern was observed in the expression of the anti-inflammatory gene IL-4. The transcripts of genes associated with barrier functions (ZO-1 and Ocln) were significantly up-regulated in the 5% TM treatment (P < 0.05). However, the activity of digestive enzymes (protease and lipase) was not different among all treatments (P > 0.05). Furthermore, the alteration of intestinal microbial communities was observed with increasing dietary TM levels. Higher genus abundance of Bacillus was observed in the TM treatments compared to that in the FM treatment (P < 0.05), and the relative abundance of Plesiomonas tended to decrease in the 5% TM and 10% TM treatments. In conclusion, substituting fish meal with 5% TM can improve the growth and intestinal health of spotted seabass, while 15% TM had no negative effects on fish. However, excess dietary TM (20%) inhibits growth, causes histopathological damage, and alters the composition of intestinal microbial community in L. maculatus. According to the results of the quadratic regression model, the level of fishmeal substitution by TM in the diet of spotted seabass should not be greater than 7.31%.

Recently, research has confirmed that jasmine tea may help improve the depressive symptoms that are associated with psychiatric disorders. Our team previously found that jasmine tea improved the depressive-like behavior that is induced by chronic unpredictable mild stress (CUMS) in Sprague Dawley (SD) rats. We hypothesized that the metabolic disorder component of depression may be related to the gut microbiota, which may be reflected in the metabolome in plasma. The influence of jasmine tea on gut microbiota composition and the association with depressive-related indexes were explored. Furthermore, the metabolites in plasma that are related to the gut microbiota were identified. SD rats were treated with control or CUMS and administrated jasmine tea for 8 weeks. The 16S rRNA gene amplicon sequencing was used to analyze the gut microbiota in feces samples, and untargeted metabolomics was used to analyze the metabolites in plasma. The results found that jasmine tea significantly ameliorated the depressive behavior induced by CUMS, significantly improved the neurotransmitter concentration (BDNF and 5-HT), and decreased the pro-inflammation levels (TNF-α and NF-κB). The intervention of jasmine tea also alleviated the dysbiosis caused by CUMS; increased the relative abundance of Bacteroides, Blautia, Clostridium, and Lactobacillus; and decreased Ruminococcus and Butyrivibrio in the CUMS-treated rats. Furthermore, the serum metabolites of the CUMS-treated rats were reversed after the jasmine tea intervention, i.e., 22 were up-regulated and 18 were down-regulated, which may have a close relationship with glycerophospholipid metabolism pathways, glycine serine and threonine metabolism pathways, and nicotinate and nicotinamide metabolism pathways. Finally, there were 30 genera of gut microbiota related to the depressive-related indexes, and 30 metabolites in the plasma had a strong predictive ability for depressive behavior. Potentially, our research implies that the intervention of jasmine tea can ameliorate the depression induced by CUMS via controlling the gut flora and the host’s metabolism, which is an innovative approach for the prevention and management of depression.

In this paper, the singular transmission properties of electromagnetic waves in one-dimensional PT-symmetric triangular finite periodic optical waveguide networks are investigated. We find that the transmission properties of electromagnetic waves differ significantly depending on whether the imaginary part of the system’s Bloch phase is zero or non-zero. Based on this, the generalized passbands and bandgaps of the PT-symmetric optical waveguide network are defined, and its generalized band structure is presented. Furthermore, we discover that electromagnetic waves incident within the frequency range of generalized bandgaps, where transmittance approaches zero, exhibit a reciprocal relationship between left and right reflectance. The system can generate interesting phenomena such as bidirectional total reflection, unidirectional super reflection, and unidirectional no reflection at these frequencies. It is also demonstrated that the frequency positions of these phenomena can be flexibly controlled by adjusting the length of the PT-symmetric waveguide and the imaginary part of its refractive index. These research findings offer a scientific basis for developing highly sensitive and multifunctional optical filters and laser reflectors.

Objective: The purpose of our study was to examine risk factors for venous thromboembolism (VTE) and VTE associated mortality in elderly acute lymphocytic leukemia (ALL) patients receiving different treatment options. Methods: We analyzed data from the United States SEER-Medicare database (2007–2015) for patients ≥65 years diagnosed with ALL. Data were stratified by treatment options into three groups as chemotherapy: the use of antimetabolites, anthracyclines, alkylating agents or vinca alkaloids; other treatment: the use of corticosteroids/tyrosine kinase inhibitors without chemotherapy; and no treatment. Logistic regression was used to examine risk factors for VTE and Cox proportional regression was used to evaluate Hazard Ratios (HRs) for the effect of VTE on mortality in ALL patients. Results: In a cohort of 1088 elderly ALL patients, 17.4 % patients had a diagnosis of VTE. VTE was diagnosed in 27.7 % of 159 patients who received chemotherapy, 16.2 % of 328 patients who received other treatment, and 15.3 % of 601 patients who did not receive any treatment (p

ABSTRACT: This study aimed to investigate the effect of stevia residue (STER) on the production performance, egg quality and nutrition, antioxidant ability, immune responses, gut morphology and microbiota of laying hens during the peak laying period. A total of 270 Yikoujingfen NO. 8 laying hens (35 wk of age) were randomly divided into 5 treatments. The control group fed a basal diet and groups supplemented with 2, 4, 6, and 8% STER. The results showed that STER significantly increased egg production, the content of amino acids (alanine, proline, valine, ornithine, asparagine, aspartic acid, and cysteine) in egg whites, and decreased the yolk color (P < 0.05). Additionally, STER significantly increased acetate, HOMOγ linolenic acid and cis-13, 16-docosadienoic acid levels in egg yolk (P < 0.05). IL-2, IL-4, and IL-10 levels in serum significantly increased by STER (P < 0.05), while IL-1β significantly decreased (P < 0.05). STER also increased total antioxidant activity (T-AOC) in the liver and estradiol level in the oviduct (P < 0.05), but decreased the cortisol level in the oviduct (P < 0.05). For the intestinal morphology, the jejunal villus height and crypt-to-villus (V:C) significantly increased by STER (P < 0.05). STER increased the relative abundance of Actinobacteriota (P < 0.05), while deceased Proteobacteria, Desulfobacterota, and Synergistota (P < 0.05). In conclusion, STER improved egg production, quality and nutrition, improved the immune responses, antioxidant capabilities, estrogen level, gut morphology, and increased the relative abundance of beneficial bacteria while decreased the harmful bacteria. Among all treatments, 4 and 6% STER supplementation yielded the most favorable results in terms of enhancing production performance, egg nutrition, gut health, and immune capabilities in laying hens.

Bellamya purificata is an important medicinal value and economically farmed species in China. However, because little is known about the genetic characteristics of this species, the utilization of high-quality germplasm resources is hindered. The study examined the genetic differentiation between, and the structure of 12 B. purificata populations in Guangxi using 7 microsatellite DNA markers. High genetic diversity occurred in each population, with mean observed heterozygosity 0.655 and a mean expected heterozygosity 0.832. Analysis of molecular variance reveals genetic diversity to be greater within (95.2%) than among populations (4.8%). Genetic differentiation between populations is weak (Fst = 0.048, P < 0.001), with mixing of genetic clusters prevalent at the level of the individual. Genetic flow exists between populations (Nm = 3.084-11.778), with Longshui and Guilin populations exchanging frequently. A Mantel test reveals a low correlation between geographic and genetic distances (r = 0.2482, P < 0.071), suggesting that dispersal between neighboring populations facilitates population exchange. No significant heterozygosity excess was observed for any population (P > 0.05), indicating a lack of recent genetic bottlenecks. The results provide important genetic information for B. purificata, and data for potential germplasm discovery and aquaculture development.

Abstract Rapid identification of pathogens is critical for early and appropriate treatment of bloodstream infections. The various culture‐independent assays that have been developed often have long turnaround times, low sensitivity and narrow pathogen coverage. Here, we propose a new multiplex PCR assay, MeltArray, which uses intact microbial cells as the source of genomic DNA (gDNA). The successive steps of the MeltArray assay, including selective lysis of human cells, microbial cell sedimentation, microbial cellular DNA extraction, target‐specific pre‐amplification and multiplex PCR detection, allowed the detection of 35 major bloodstream infectious pathogens in whole blood within 5.5 h. The limits of detection varied depending on the pathogen and ranged from 1 to 5 CFU/mL. Of 443 blood culture samples, including 373 positive blood culture samples and 70 negative blood culture samples, the MeltArray assay showed a sensitivity of 93.8% (350/373, 95% confidence interval [CI] = 90.7%–96.0%), specificity of 98.6% (69/70, 95% CI = 91.2%–99.9%), positive predictive value of 99.7% (95% CI = 98.1%–99.9%), and negative predictive value of 75.0% (95% CI = 64.7%–83.2%). The MeltArray detection results of 16 samples differed from MALDI–TOF and were confirmed by Sanger sequencing. Further testing of 110 whole blood samples from patients with suspected bloodstream infections using blood culture results revealed that the MeltArray assay had a clinical sensitivity of 100% (9/9, 95% CI = 62.8%–100.0%), clinical specificity of 74.5% (70/94, 95% CI = 64.2%–82.7%), positive predictive value of 27.3% (95% CI = 13.9%–45.8%), and negative predictive value of 100.0% (95% CI = 93.5%–100.0%). Compared with metagenomic next‐generation sequencing, the MeltArray assay displayed a positive agreement of 85.7% (6/7, 95% CI = 42.0%–99.2%) and negative agreement of 100.0% (4/4, 95% CI = 39.6%–100.0%). We conclude that the MeltArray assay can be used as a rapid and reliable tool for direct identification of pathogens in bloodstream infections.

Rice flower carp (Cyprinus carpio rubrofuscus) has high economic value because of its tender meat. However, a comprehensive scientific evaluation of the meat quality and nutritional value of rice flower carp is still needed. At the same time, because of its fast growth and strong disease resistance, rice flower carp is widely popularized in rice field culture but without any research comparing its quality with the pond culture method. Although rice farming has high ecological value, the fish yield is low and its specifications are abnormal, which cannot guarantee the stability and safety of the commercial fish supply and limit the potential rice flower carp industrial benefits. In addition, some studies have shown that fish muscle quality can be affected by environmental conditions. This study aimed to comprehensively evaluate the muscle quality and nutritional value of the rice flower carp and investigate the relationships between the nutritional values and its culture conditions, providing data to increase the rice flower carp yield, economic efficiency, and farmed varieties available. Therefore, 6 000 Quanzhou rice flower carp (2.35±0.08 g) were randomly divided into ponds and rice field groups for the experiment (three replicates per group, with a density of 15 000/hm2). The pond culture group was fed with 3% of the commercially established everyday food per fish weight, while the rice field group was not fed. After 12 weeks, the fish were submitted to a 24 h period without food and anesthetized using MS-222 (USA, Sigma). The length and weight of 100 fish were measured for each treatment. For the rice field group and pond group, respectively, the lengths were (13.56±0.49) cm and (14.10±0.23) cm, and the weights were (73.19±7.02) g and (101.20±4.57) g. The muscle quality of 30 fish from each treatment was measured, including basic nutritional components, texture characteristics, and amino acid and fatty acid compositions. The nutritional level was compared between the pond and rice field groups using the FAO/WHO amino acid score, whole egg protein comparison, protein amino acid score (AAS), chemical score (CS), and essential amino acid index (EAAI). Moreover, no significant differences between the two culture methods were observed in relation to the total ash (P > 0.05). The crude protein and crude fat contents in the rice field group were significantly lower than in the pond group (P < 0.05), while moisture was significantly higher (P < 0.05). The viscosity of the rice field group was significantly lower than that of the pond group (P < 0.05), but the cohesion and shear force were significantly higher than those of the pond group (P < 0.05). There was no significant difference in the other texture indexes (P > 0.05). Essential amino acids (EAA) in both groups met the FAO/WHO standard. Among the 18 amino acids measured, the total amino acids (TAA), delicious amino acids (DAA), essential and nonessential amino acids (NEAA) were significantly lower in rice field conditions than in pond (P < 0.05), while the EAA/TAA and EAA/NEAA ratios were significantly lower in the pond group (P < 0.05). According to the amino acid score (AAS) and chemical score (CS), glutamic acid (Glu) was the most common amino acid in both groups, while the first and second limiting amino acids were tryptophan (Trp) and valine (Val). Among the 22 fatty acids observed, the contents of tridecanoic, pentadecanoic, palmitoleic, heptadecanoic, and docosatetraenoic acids were not significantly different between the two groups (P > 0.05). In contrast, the contents of linoleic, linolenic, and arachidonic acids in the pond group were significantly higher than those in the rice field group (P < 0.05), while 14 other fatty acids showed significantly lower contents in the pond group (P < 0.05). The monounsaturated fatty acid (MUFA) contents in the pond group were significantly higher (P < 0.05), while the EPA+DHA and n-3PUFA/n-6PUFA were significantly lower than those in the rice field group (P < 0.05). Overall, the contents of four main flavor amino acids (glutamic acid, glycine, alanine, and aspartic acid) in the rice field group were significantly lower than those in the pond group (P < 0.05). In conclusion, rice flower carp reared in both pond and rice field is a high-quality protein source. However, different cultural environments significantly influence the rice flower carp muscle nutritional value and quality, wherein a higher nutrient composition and amino acid score were observed in the pond environment. Concerning the fatty acids content, the muscle of rice flower carp reared in rice fields had higher EPA+DHA content and N-3/N-6 polyunsaturated fatty acid ratio, which is more suitable for people with hyperlipidemia and cardiovascular diseases. In addition, in terms of texture, the muscle of rice flower carp is chewier under the rice field rearing condition. Nevertheless, N-3PUFA shortages were observed in both culture conditions. Besides, fish in the pond group had better muscle nutrition than the rice field group. Different culture conditions can change rice flower carp's fatty acid composition and content to a certain extent, but none of the two conditions tested here could completely allay the lower N-3PUFA problem. Therefore, increasing the N-3PUFA content of rice flower carp is the key to improving its nutritional value, and pond culture conditions make this process easier to be manually controlled.

In order to understand the changes of fungal community and metabolites in mildew Liupao tea, the fungal diversity of mildew Liupao tea samples (GGZ) and normal Liupao tea samples stored in bamboo basket (BDL) were analyzed by Illumina high-throughput sequencing technology, and ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to analyze the metabolites in these samples. Further, pathway enrichment analysis was performed on the significantly differential metabolites, and the correlation between the differential metabolites and the differential microorganisms was calculated. The results showed that the most abundant fungi in mildew Liupao tea were Ascomycota and Basidiomycota in phylum level, Aspergillus and Wallemia in genus level. Aspergillus and Penicillium belonging to Ascomycota were more abundant in BDL. Two of the dominant fungi related to mildew in Liupao tea, A. Ruber and W. sebi, showed significantly (P

Electric power resources are the core energy for a country’s economic development and growth. China is at the peak of electric energy consumption at this stage. Improving the accuracy and integrity of electric energy metering technology is of great significance for evaluating the use and consumption of resources in China. Under the background of artificial intelligence, this research analyzes and studies the integrated module, demand status, performance optimization, and coupling degree of the electric energy metering system (hereinafter referred to as EES) through the application of two different types of sensors. The results show that the application of intelligent sensors has a better integration effect with the system management of electric energy metering, which plays a very important role in promoting the sustainable development of automation and informatization of the EES.

IntroductionThe chronological age (CA) cannot precisely reflect the health status. Our study aimed to establish a model of kidney biological age to evaluate kidney function more elaborately.MethodsThe modeling group was used to establish the model, consisting of 1,303 respondents of the China Health and Retirement Longitudinal Study (CHARLS). The biological age of the kidney (BA) was constructed by principal component analysis (PCA) and Klemera and Doubal’s method (KDM) with the 1,303 health respondents.ResultsPCA was chosen as the best method for our research step by step. The test group was used to apply the model. (a) BA of the kidney can distinguish respondents with from without kidney disease. (b) BA of the kidney was significantly different in various levels of kidney function. The BA of the eGFR

Astaxanthin (AST) is a feed additive applied in aquaculture, which has been proved to promote the growth performance, antioxidant capacity and immunity of crayfish (Procambarus clarkii), an important economic fishery species in China. However, the underlying mechanism of improved antioxidant capacity of AST in crayfish remains unknown. In this study, changes of antioxidant activity, transcriptome and metabolome in crayfish hepatopancreas were analyzed after feeding with AST. The results showed that AST could improve the antioxidant capacity of crayfish via increasing antioxidant enzymes activity and reducing malondialdehyde content. Transcriptomic analysis revealed that immune system, cell death and disease, mitochondrial respiration and oxidative phosphorylation pathways were altered with AST feeding. AST significantly increased total cholesterol level indicated the metabolism of crayfish was affected. Metabolomic analysis revealed the alteration of mineral adsorption, carbon and amino acid metabolisms, and fatty acid biosynthesis. Conjoint analysis of transcriptome and metabolome suggested that AST predominantly regulated amino acid and fatty acid metabolisms. Taken together, AST acts on crayfish mainly through improving antioxidant capacity and modulating amino acid and fatty acid metabolisms.

Chronic kidney disease (CKD) is a major complication of diabetes mellitus (DM). Inflammation is an essential component in the process of CKD progression in patients with DM. Diet is a significant determinant of systemic inflammation levels. However, the association between the dietary inflammatory index (DII) and CKD in individuals with DM remains largely unknown; therefore, the aim of this study was to explore whether the DII is linked to the prevalence of CKD in patients with DM. The research method was as follows: first, data from the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2018 were obtained. There were 7,974 participants in our study. These individuals were then classified into three groups according to DII tertiles (T1-T3), with each group consisting of 2,658 participants. Logistic regression analysis was employed to examine whether there was a connection between the DII and CKD. We observed a significant association between the DII and the prevalence of CKD in individuals with DM. After full adjustment for age, sex, ethnicity, smoking, drinking, body mass index (BMI), triglyceride (TG), total cholesterol (TC), metabolic equivalents (METs), energy intake, hypoglycemic medications, hypertension, and cardiovascular disease (CVD), the group with a higher DII had a greater frequency of CKD (T2 group: OR: 1.40; 95% CI: 1.10–1.76; p = 0.006; T3 group: OR: 1.67; 95% CI: 1.29–2.17; p

Chronic hepatitis B virus (HBV) infection remains one of the major global public health concerns, and it develop into liver fibrosis, cirrhosis, and hepatocellular carcinoma. Recent evidence suggests that endosomal and autophagic vesicles are beneficial for HBV replication. However, it has not been well elucidated how HBV exploits such intracellular vesicle systems for its replication. RAB5A, a member of small GTPase family, plays crucial roles in early endosome biogenesis and autophagy initiation. We observed that RAB5A mRNA and protein levels were significantly increased in HBV-expressing hepatoma cell lines as well as in liver tissue samples from chronic HBV-infected patients. Moreover, RAB5A silencing inhibited HBV replication and subviral particle (SVP) expression significantly in HBV-transfected and -infected hepatoma cells, whereas RAB5A overexpression increased them. Mechanistically, RAB5A increases HBV replication through enhancement of early endosome (EE) – late endosome (LE) activation by interacting with EEA1, as well as enhancing autophagy induction by interacting with VPS34. Additionally, HBV infection enhances RAB5A-mediated dual activation of EE-LE system and autophagy. Collectively, our findings highlight that HBV utilizes RAB5A-mediated dual activation of endosomal and autophagic vesicle pathways for its own replication and persistence. Therefore, RAB5A is a potential target for chronic HBV infection treatment.

Objective: To predict COVID-19 severity by building a prediction model based on the clinical manifestations and radiomic features of the thymus in COVID-19 patients. Method: We retrospectively analyzed the clinical and radiological data from 217 confirmed cases of COVID-19 admitted to Xiangyang NO.1 People's Hospital and Jiangsu Hospital of Chinese Medicine from December 2019 to April 2022 (including 118 mild cases and 99 severe cases). The data were split into the training and test sets at a 7:3 ratio. The cases in the training set were compared in terms of clinical data and radiomic parameters of the lasso regression model. Several models for severity prediction were established based on the clinical and radiomic features of the COVID-19 patients. The DeLong test and decision curve analysis (DCA) were used to compare the performances of several models. Finally, the prediction results were verified on the test set. Result: For the training set, the univariate analysis showed that BMI, diarrhea, thymic steatosis, anorexia, headache, findings on the chest CT scan, platelets, LDH, AST and radiomic features of the thymus were significantly different between the two groups of patients (P < 0.05). The combination model based on the clinical and radiomic features of COVID-19 patients had the highest predictive value for COVID-19 severity [AUC: 0.967 (OR 0.0115, 95%CI: 0.925-0.989)] vs. the clinical feature-based model [AUC: 0.772 (OR 0.0387, 95%CI: 0.697-0.836), P < 0.05], laboratory-based model [AUC: 0.687 (OR 0.0423, 95%CI: 0.608-0.760), P < 0.05] and model based on CT radiomics [AUC: 0.895 (OR 0.0261, 95%CI: 0.835-0.938), P < 0.05]. DCA also confirmed the high clinical net benefits of the combination model. The nomogram drawn based on the combination model could help differentiate between the mild and severe cases of COVID-19 at an early stage. The predictions from different models were verified on the test set. Conclusion: Severe cases of COVID-19 had a higher level of thymic involution. The thymic differentiation in radiomic features was related to disease progression. The combination model based on the radiomic features of the thymus could better promote early clinical intervention of COVID-19 and increase the cure rate.

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection‐caused coronavirus disease 2019 (COVID‐19) is a global crisis with no satisfactory therapies. Vitamin D3 (VD3) is considered a potential candidate for COVID‐19 treatment; however, little information is available regarding the exact effects of VD3 on SARS‐CoV‐2 infection and the underlying mechanism. Herein, we confirmed that VD3 reduced SARS‐CoV‐2 nucleocapsid (N) protein‐caused hyperinflammation in human bronchial epithelial (HBE) cells. Meanwhile, VD3 inhibited the NOD‐like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation in N protein‐overexpressed HBE (HBE‐N) cells. Notably, the inhibitors of caspase‐1, NLRP3, and NLRP3 or caspase‐1 small interference RNA (siRNA) enhanced VD3‐induced NLRP3 inflammasome inactivation, with subsequent suppression of interleukin‐6 (IL6) and IL1β release in HBE‐N cells, which were abolished by the NLRP3 agonist. Moreover, VD3 increased NLRP3 ubiquitination (Ub‐NLRP3) expression and the binding of the VDR with NLRP3, with decreased BRCA1/BRCA2‐containing complex subunit 3 (BRCC3) expression and NLRP3‐BRCC3 association. VD3‐induced Ub‐NLRP3 expression, NLRP3 inflammasome inactivation, and hyperinflammation inhibition were improved by the BRCC3 inhibitor or BRCC3 siRNA, which were attenuated by the vitamin D receptor (VDR) antagonist or VDR siRNA in HBE‐N cells. Finally, the results of the in vivo study in AAV‐Lung‐enhanced green fluorescent protein‐N‐infected lungs were consistent with the findings of the in vitro experiment. In conclusion, VD3 attenuated N protein‐caused hyperinflammation by inactivating the NLRP3 inflammasome partially through the VDR‐BRCC3 signaling pathway.

Objective: To collect the clinical, pathological, and computed tomography (CT) data of 143 accepted surgical cases of pancreatic body tail cancer (PBTC) and to model and predict its prognosis. Methods: The clinical, pathological, and CT data of 143 PBTC patients who underwent surgical resection or endoscopic ultrasound biopsy and were pathologically diagnosed in Xiangyang No.1 People's Hospital Hospital from December 2012 to December 2022 were retrospectively analyzed. The Kaplan-Meier method was adopted to make survival curves based on the 1 to 5 years’ follow-up data, and then the log-rank was employed to analyze the survival. According to the median survival of 6 months, the PBTC patients were divided into a group with a good prognosis (survival time ≥ 6 months) and a group with a poor prognosis (survival time

SOX2 is a transcription factor belonging to the SOX gene family, whose activity has been associated with the maintenance of the stemness and self-renewal of embryonic stem cells (ESCs), as well as the induction of differentiated cells into induced pluripotent stem cells (iPSCs). Moreover, accumulating studies have shown that SOX2 is amplified in various cancers, notably in esophageal squamous cell carcinoma (ESCC). In addition, SOX2 expression is linked to multiple malignant processes, including proliferation, migration, invasion, and drug resistance. Taken together, targeting SOX2 might shed light on novel approaches for cancer therapy. In this review, we aim to summarize the current knowledge regarding SOX2 in the development of esophagus and ESCC. We also highlight several therapeutic strategies for targeting SOX2 in different cancer types, which can provide new tools to treat cancers possessing abnormal levels of SOX2 protein.

ABSTRACTBackground: National guidelines recommend cancer genetic risk assessment (CGRA) (i.e. genetic counseling prior to genetic testing) for women at increased risk for hereditary breast and ovarian cancer (HBOC). Less than one-half of eligible women obtain CGRA, leaving thousands of women and their family members without access to potentially life-saving cancer prevention interventions.Purpose: The Genetic Risk Assessment for Cancer Education and Empowerment Project (GRACE) addressed this translational gap, testing the efficacy of a tailored counseling and navigation (TCN) intervention vs. a targeted print brochure vs. usual care on CGRA intentions. Selected behavioral variables were theorized to mediate CGRA intentions.Methods: Breast and ovarian cancer survivors meeting criteria for guideline-based CGRA were recruited from three state cancer registries (N = 654), completed a baseline survey, and were randomized. TCN and targeted print arms received the brochure; TCN also participated in a tailored, telephone-based decision coaching and navigation session grounded in the Extended Parallel Process Model and Ottawa Decision Support Framework. Participants completed a one-month assessment. Logistic regression was used to compare the rate of CGRA intentions. CGRA intentions and theorized mediator scores (continuous level variables) were calculated using mixed model analysis.Results: CGRA intentions increased for TCN (53.2%) vs. targeted print (26.7%) (OR = 3.129; 95% CI: 2.028, 4.827, p

Abstract Background Implementation of physical activity strategies in older populations may be influenced by underlying psychosocial and gender-based factors to physical activity. We explored associations between these factors and physical activity behaviors and technology among older men and women. Methods Community older adults underwent echocardiography and interviewer administered questionnaires that collected physical activity habits, self-motivation, self-empowerment and smartphone usage patterns associated with physical activity. Aerobic capacity was denoted by VO2max (High VO2 was defined as VO2 > 35 (ml/kg/min) for men or VO2 > 27 (ml/kg/min) for women). Results Among 180 participants (mean age 77 (71–80) years; 43% females), 101 (56.1%) had a low VO2max. Barriers to activity were lack of time (27.8%), tiredness (26.7%), affordability (12.8%) and pain while exercising (12.2%). Compared to participants with high VO2max, those with low VO2max were less likely to report feeling good post-exercise (70.3% vs 86.1%, adjusted p = 0.041) and express barriers to exercise (72.3% vs 88.6%, adjusted p = 0.017). Compared to men, women were more likely to express motivation for exercise if they were guided by an instructor (20.5% vs 1.96%, adjusted p = 0.027), less likely to prefer control over exercise type and difficulty (57.7% vs 82.4%, adjusted p = 0.001), express interest in smartphone apps (7.84% vs 24.4%, adjusted p = 0.01) and participate in apps-guided exercise (10.3% vs 29.4%, adjusted p = 0.001). Major factors that motivated the use of smartphone applications to manage individual health were financial incentives (23.9%) and guidance on exercise routines (21.1%) while the reveal of personal information was a major deterrent (28.3%). Conclusions We observed differences in physical activity motivation, empowerment and technology use based on gender and functional status. Tailoring physical activity strategies, including digital health strategies, that target psychosocial and gender-based factors may improve activity participation in older adults.

Coronavirus disease 2019 (COVID-19) caused by the emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has set off a global pandemic. There is an urgent unmet need for safe, affordable, and effective therapeutics against COVID-19. In this regard, drug repurposing is considered as a promising approach. We assessed the compounds that affect the endosomal acidic environment by applying human angiotensin-converting enzyme 2 (hACE2)- expressing cells infected with a SARS-CoV-2 spike (S) protein-pseudotyped HIV reporter virus and identified that obatoclax resulted in the strongest inhibition of S protein-mediated virus entry. The potent antiviral activity of obatoclax at nanomolar concentrations was confirmed in different human lung and intestinal cells infected with the SARS-CoV-2 pseudotype system as well as clinical virus isolates. Furthermore, we uncovered that obatoclax executes a double-strike against SARS-CoV-2. It prevented SARS-CoV-2 entry by blocking endocytosis of virions through diminished endosomal acidification and the corresponding inhibition of the enzymatic activity of the endosomal cysteine protease cathepsin L. Additionally, obatoclax impaired the SARS-CoV-2 S-mediated membrane fusion by targeting the MCL-1 protein and reducing furin protease activity. In accordance with these overarching mechanisms, obatoclax blocked the virus entry mediated by different S proteins derived from several SARS-CoV-2 variants of concern such as, Alpha (B.1.1.7), Beta (B.1.351), and Delta (B.1.617.2). Taken together, our results identified obatoclax as a novel effective antiviral compound that keeps SARS-CoV-2 at bay by blocking both endocytosis and membrane fusion. Our data suggested that obatoclax should be further explored as a clinical drug for the treatment of COVID-19.

Previous studies have revealed multiple tissue- or cell-specific or enriched miRNA profiles. However, miRNA profiles enriched in hepatic cell types and their effect on HBV replication have not been well elucidated. In this study, primary human hepatocytes (PHHs), Kupffer cells (KCs), liver sinusoidal endothelial cells (LSECs), and hepatic stellate cells (HSCs) were prepared from liver specimens of non-HBV-infected patients. Four hepatic cell type-enriched miRNA profiles were identified from purified liver cells miRNA microarray assay. The results revealed that 12 miRNAs, including miR-122-5p and miR-192-3p were PHH-enriched; 9 miRNAs, including miR-142-5p and miR-155-5p were KC-enriched; 6 miRNAs, including miR-126-3p and miR-222-3p were LSEC-enriched; and 14 miRNAs, including miR-214-3p and miR-199a-3p were HSC-enriched. By testing the effect of 11 PHH-enriched miRNAs on HBV production, we observed that miR-192-3p had the greatest pro-virus effect in hepatic cell lines. Moreover, we further found that miR-192-3p promoted HBV replication and gene expression through inhibiting Akt/mTOR signalling by direct targeting of ZNF143 in HepG2.2.15 cells. Additionally, the serum and hepatic miR-192-3p expression levels were significantly higher in chronic hepatitis B patients than in healthy controls and serum miR-192-3p positively correlated with the serum levels of HBV DNA and HBsAg. Collectively, we identified miRNA profiles enriched in four hepatic cell types and revealed that PHH-enriched miR-192-3p promoted HBV replication through inhibiting Akt/mTOR signalling by direct targeting of ZNF143 in hepatic cell lines. Our study provides a specific perspective for the role of hepatic cell type-enriched miRNA in interaction with viral replication and various liver pathogenesis.

Carbon pool management index (CPMI) can be used to indicate the stability of soil carbon and assess the effect of anthropogenic activities on soil carbon dynamics of different land-use types. The impacts of land-use types on CPMI are usually evaluated through soil organic carbon (SOC) fractions and contents, which are closely related to arbuscular mycorrhizal fungi (AMF) and its secretory product (Glomalin-related soil protein, GRSP). However, most previous studies focused on the effects of GRSP on SOC fractions, and few studies paid attention to the influence of AMF to SOC fractions and CPMI. This study was to investigate the interrelationship between SOC fractions and contents, AMF growth and colonization status, GRSP contents and CPMI at the soil depths from 0 to100 cm among four land-use types (woodland, grassland, farmland, abandoned land) in Songnen Grassland, Northeast China. The results showed that the content of SOC in woodland was 2.35 times higher than that of abandoned land, with an order as follow: woodland > grassland > farmland > abandoned land. The readily oxidizable organic carbon content in soil ranged from 1.12 to 1.31 g kg−1, with a sequence of from high to low: woodland > farmland > grassland > abandoned land. Carbon in GRSP accounted for 4.57–14.91% of SOC in the 0–100 cm soil depths. The structural equation modeling revealed that land-use types had two pathways to affect CPMI through GRSP: (i) directly via total GRSP content; (ii) or indirectly via hyphal length density of AMF. This study demonstrates the effects of land-use on soil organic carbon and carbon pool management index through glomalin related soil protein and other colonization traits of arbuscular mycorrhizal fungi, and suggests the suitable management methods of land use for future carbon-neutral policy in farming-pastoral ecotone area of Northeastern China.