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Abstract Background In locally advanced, operable esophageal squamous cell carcinoma (ESCC), neoadjuvant immunochemotherapy (nICT) has shown results that are somewhat comparable to those of standard neoadjuvant chemoradiotherapy (nCRT). The impact of these neoadjuvant treatments on survival outcomes, however, has yet to be elucidated. Methods This study included 489 patients with locally advanced ESCC who underwent surgery at Sichuan Cancer Hospital after receiving neoadjuvant treatment between June 2017 and September 2023. Patients were categorized into nCRT and nICT groups based on whether they received neoadjuvant treatment. To mitigate potential biases and balance covariates between the two cohorts, 1:2 propensity score matching (PSM) was conducted using a caliper width of 0.05. Results After PSM, the baseline characteristics of the 360 patients remained balanced between the two groups. The findings indicated a superior pathological response in the nCRT group, as evidenced by significantly greater rates of complete response (32.87% vs 14.58%, P

Abstract The anterior cingulate cortex (ACC) is one of the critical brain areas for processing noxious information. Previous studies showed that peripheral nerve injury induced broad changes in the ACC, contributing to pain hypersensitivity. The neurons in layer 3 (L3) of the ACC receive the inputs from the mediodorsal thalamus (MD) and form the feedforward inhibition (FFI) microcircuits. The effects of peripheral nerve injury on the MD-driven FFI in L3 of ACC are unknown. In our study, we record the enhanced excitatory synaptic transmissions from the MD to L3 of the ACC in mice with common peroneal nerve ligation, affecting FFI. Chemogenetically activating the MD-to-ACC projections induces pain sensitivity and place aversion in naive mice. Furthermore, chemogenetically inactivating MD-to-ACC projections decreases pain sensitivity and promotes place preference in nerve-injured mice. Our results indicate that the peripheral nerve injury changes the MD-to-ACC projections, contributing to pain hypersensitivity and aversion.

Abstract Background Sarcopenia is an important indicator of ill health and is linked to increased mortality and a reduced quality of life. Age‐associated muscle mass indices provide a critical tool to help understand the development of sarcopenia. This study aimed to develop sex‐ and age‐specific percentiles for muscle mass indices in a Chinese population and to compare those indices with those from other ethnicities using the National Health and Nutrition Examination Survey (NHANES) data. Methods Whole‐body and regional muscle mass was measured by dual‐energy X‐ray absorptiometry (DXA) in participants of the China Body Composition Life‐course (BCL) study (17 203 healthy Chinese aged 3–60 years, male 48.9%) and NHANES (12 663 healthy Americans aged 8–59 years, male 50.4%). Age‐ and sex‐specific percentile curves were generated for whole‐body muscle mass and appendicular skeletal muscle mass using the Generalized Additive Model for Location Scale and Shape statistical method. Results Values of upper and lower muscle mass across ages had three periods: an increase from age 3 to a peak at age 25 in males (with the 5th and 95th values of 41.5 and 66.4 kg, respectively) and age 23 in females (with the 5th and 95th values of 28.4 and 45.1 kg, respectively), a plateau through midlife (30s–50s) and then a decline after their early 50s. The age at which muscle mass began to decline was 52 years in men with the 5th and 95th percentile values of 43.5 and 64.6 kg, and 51 years in women with the 5th and 95th percentile values of 31.6 and 46.9 kg. Appendicular skeletal muscle mass decreased earlier than whole body muscle mass, especially leg skeletal muscle mass, which decreased slightly after age 49 years in both sexes. In comparison with their US counterparts in the NHANES, the Chinese participants had lower muscle mass indices (all P

Abstract Inflammation plays an important role in depression, and the neutrophil-to-albumin ratio (NPAR) is a cost-effective and readily available novel biomarker of inflammation. The association between NPAR and depression is unclear; therefore, to assess the relationship between NPAR and depression, we conducted a cross-sectional study of 33,768 participants ≥ 18 years of age from the 2005–2018 NHANES database. NPAR was calculated as Neutrophil percentage (in total WBC count) (%) × 100/Albumin (g/dL). Multivariate logistic regression models were used to test the independent association between NPAR and depression, adjusting for demographic factors, education, smoking status, alcohol consumption, hypertension, diabetes mellitus, body mass index, the ratio of income to poverty, and history of cardiovascular disease. Results showed that NPAR was significantly and positively associated with depression. When NPAR were analyzed as a categorical variable, there was a 20% increase in the prevalence of depression in the quartile with the highest NPAR compared to the quartile with the lowest NPAR (OR 1.20[95% CI 1.06, 1.36]). Smoothed curve fitting and threshold effect analyses also showed a positive association between NPAR and depression, with an inflection point for threshold and saturation effects of 12.65. NPAR was positively associated with the likelihood of developing depression when NPAR > 12.65 (OR 1.06[95% CI 1.04, 1.09]). The results of subgroup analyses and interaction tests indicated that smoking status had a significant effect on the relationship between NPAR and depression (P

Abstract Background The reference values of eNO have certain differences among people of different countries and races. We aimed to obtain the reference value of eNO in healthy children and adolescents (6–18 years old) in China and to explore the associations between the reference values with ages, gender, heights, BMI, and regions. Methods We measured FeNO50 levels in 5949 healthy Chinese children and adolescents, FeNO200 and CaNO levels in 658 participants from 16 provinces of 7 administrative areas in China aged 6–18. All persons were studied after obtaining informed consent from children and their parents. Results The mean FeNO50 of 5949 Chinese children and adolescents aged 6–18 years was 14.1 ppb, with a 95% confidence interval of 1-38.1 ppb. The mean FeNO200 of 658 persons was 6.9 ppb with a 95% upper confidence interval of 15.0 ppb, and the mean CaNO was 3.0 ppb with a 95% upper confidence interval of 11.2 ppb. In the 6–11 age group, age and height were correlated with the logarithm of FeNO50 (P 0.05). The logarithm of CaNO was correlated with gender (P

Abstract Background Rapid sequence intubation (RSI) is a crucial step in the resuscitation process for critically ill patients, and the judicious use of sedative drugs during RSI significantly influences the clinical outcomes of patients. Ketamine is a commonly used anesthetic sedative; however, its impact on the mortality of patients undergoing RSI has yielded inconsistent findings. Therefore, we conducted a systematic review and meta-analysis investigating ketamine’s role in RSI to provide insights into selecting appropriate sedatives for critically ill patients. Methods In this systematic review and meta-analysis, we conducted a systematic search on MEDLINE (PubMed), Embase, and Cochrane Central Register of Controlled Trials, without restricting to randomized controlled trials (RCTs) or cohort studies. The search was performed from inception until Dec 12, 2023, with no language restrictions. All studies comparing the use of sedatives, including ketamine, and documenting in-hospital mortality were included in this study. Results A total of 991 studies were identified, out of which 15 studies (5 RCTs and 10 cohort studies) involving 16,807 participants fulfilled the inclusion criteria. No significant impact on in-hospital mortality was observed with the use of ketamine compared to other drugs during RSI (OR 0.90, 95%CI 0.72 to 1.12). Low-quality evidence suggested that ketamine might reduce mortality within the first seven days of hospitalization (OR 0.42, 95%CI 0.19 to 0.93), but it may also have a potential effect on prolonging ICU-free days at day 28 (MD -0.71, 95%CI -1.38 to -0.05). There were no significant differences in the results of the other RSI-related outcomes, such as physiological function and adverse events. Conclusions Based on existing studies, ketamine showed no significant difference compared to other sedatives in terms of in-hospital mortality, physiological impact, and side effects following RSI. However, it may reduce mortality within 7 days while probably prolong the length of stay in the ICU. Trial registration CRD42023478020.

Abstract PANoptosis is engaged in the program of immune response and carcinogenicity. Nonetheless, the actual impacts of PANoptosis on clinical management and oncology immunity in hepatocellular carcinoma (HCC) are not fully grasped. RNA-seq-derived computations were conducted to sort out the molecular subtypes and elucidate the disparities based on PANoptosis molecules. Single-cell sequencing (scRNA-seq) tools including Cytotrace and Addmodulescore were extracted to characterize diversification potency and quantify the PANoptosis motion. Transcriptional factors were inferred by the pySCENIC package and Cellchat program scrutinized the intercellular exchange across cell compartments. The PANoptosis score system originated by incorporating 10 machine learning algorithms and 101 compositions to project clinical results and deteriorate tendencies. Circulatory PANoptosis-associated protein HSP90AA1 was determined by enzyme-linked immunosorbent assay (ELISA). HCC individuals could be categorized into low- and high-PANoptosis groups with diverse biogenic and pharmacotherapy heterogeneity. Individuals in the elevated PANoptosis subtype were characterized as “hot tumor” conveying the increased presence of immunogenicity while reiterating an explicit negative connection with tumor stemness. Compared to immune and stromal cells, cancerous cells showcased decreased PANoptosis and heightened PANoptosis malignant cell subgroups might be tied to a substantial level of genomic expression of SREBF2, JUND, GATAD1, ZBTB20, SMAD5 and implied a more aggressive potential. The PANoptosis index, derived from machine learning, has been established to provide succinct frameworks for predicting outcomes and clarified the noteworthy utility of conventional regimens, as the differentiated power of HCC occurred together with vascular invasion and hepatocellular adenoma (HCA). The experiment confirmed that the circulating HSP90AA1 was aberrantly augmented in HCC patients, thus demonstrating its potential as a discriminatory biomarker. We systematically deciphered the molecular and immune ecosystem traits of PANoptosis in bulk and scRNA-seq degrees, which may deliver advantageous insights for customized treatment, awareness of the pathological process and prognosis scrutiny for HCC patients.

Abstract In this study, pure V6O13 and nickel ion-doped V6O13 powders were synthesized by a simple hydrothermal-calcination method, and their broad-spectrum antimicrobial properties and mechanisms were investigated. The crystal structure, morphology, and chemical state of the powders were thoroughly analyzed by XRD, SEM, TEM, XPS, and UV–Vis. Their antimicrobial properties and mechanisms were evaluated by the ring of inhibition, bio-SEM, live-dead cell staining, ROS detection, and protein leakage experiments. The results showed that nickel ion doping modulated the oxygen defects of V6O13, generating more reactive oxygen species and leading to more severe oxidative stress, resulting in a broad-spectrum and highly efficient antimicrobial effect. This study also revealed the antimicrobial mechanism based on oxygen defect -induced ROS production, which caused cellular oxidative stress damage, leading to leakage of intracellular substances and cell death. This study not only demonstrates the potential of V6O13 as an efficient antimicrobial agent but also provides a strong experimental basis and theoretical support for the engineering design and optimization of novel antimicrobial materials by modulating material defects through ion doping.

Abstract Background Several abdominal obesity indices including waist circumference (WC), waist–hip ratio (WHR), visceral adiposity index (VAI), lipid accumulation product (LAP), and Chinese visceral adiposity index (CVAI) were considered effective and useful predictive markers for cardiovascular disease (CVD) in general populations or diabetic populations. However, studies investigating the associations between these indices among postmenopausal women are limited. Our study aimed to investigate the associations of the five indices with incident CVD and compare the predictive performance of CVAI with other abdominal obesity indices among postmenopausal women. Methods A total of 1252 postmenopausal women without CVD at baseline were analyzed in our investigation based on a 10-year follow-up prospective cohort study. Link of each abdominal obesity index with CVD were assessed by the Cox regression analysis and the Kaplan–Meier curve. The receiver operating characteristic (ROC) curves were drawn to compare the predictive ability for CVD. Results During the median follow-up of 120.53 months, 121 participants newly developed CVD. Compared to quartile 1 of LAP and CVAI, quartile 4 had increased risk to develop CVD after fully adjusted among postmenopausal women. When WC, VAI and CVAI considered as continuous variables, significant increased hazard ratios (HRs) for developing CVD were observed. The areas under the curve (AUC) of CVAI (0.632) was greatly higher than other indices (WC: 0.580, WHR: 0.538, LAP: 0.573, VAI: 0.540 respectively). Conclusions This study suggested that the abdominal obesity indices were associated with the risk of CVD excluded WHR and highlighted that CVAI might be the most valuable abdominal obesity indicator for identifying the high risk of CVD in Chinese postmenopausal women.

Background The incidence density of metabolic dysfunction-associated fatty liver disease (MAFLD) and the effect of a healthy lifestyle on the risk of MAFLD remain unknown. We evaluated the prevalence and incidence density of MAFLD and investigated the association between healthy lifestyle and the risk of MAFLD. Methods A cross-sectional analysis was conducted on 37,422 participants to explore the prevalence of MAFLD. A cohort analysis of 18,964 individuals was conducted to identify the incidence of MAFLD, as well as the association between healthy lifestyle and MAFLD. Cox proportional hazards regression was used to calculate the hazard ratio (HR) and 95% confidence interval (CI) with adjustments for confounding factors. Results The prevalence of MAFLD, non-alcoholic fatty liver disease, and their comorbidities were 30.38%, 28.09%, and 26.13%, respectively. After approximately 70 thousand person-years of follow-up, the incidence densities of the three conditions were 61.03, 55.49, and 51.64 per 1,000 person-years, respectively. Adherence to an overall healthy lifestyle was associated with a 19% decreased risk of MAFLD (HR, 0.81; 95% CI, 0.72 to 0.92), and the effects were modified by baseline age, sex, and body mass index (BMI). Subgroup analyses revealed that younger participants, men, and those with a lower BMI experienced more significant beneficial effects from healthy lifestyle. Conclusion Our results highlight the beneficial effect of adherence to a healthy lifestyle on the prevention of MAFLD. Health management for improving dietary intake, physical activity, and smoking and drinking habits are critical to improving MAFLD.

Abstract Background Saccharomyces cerevisiae has been considered a harmless yeast, but in recent years, increasing evidence has shown that it can cause disease in humans, especially invasive infections in infants/children and vulvovaginal infections in women. This study aimed to investigate the clinical information and antifungal susceptibility of clinical cases with S. cerevisiae and establish a foundation for the prevention and treatment of fungal infections. Methods This study was conducted from May 2018 to May 2023 at a national regional medical center in Southwest China for women and children. The demographic and clinical characteristics of patients isolated with S. cerevisiae were collected and analyzed. All the isolates were cultured on Sabouraud medium plates and identified by MALDI-TOF MS. The antifungal susceptibility of S. cerevisiae to 10 agents (amphotericin B, fluconazole, itraconazole, voriconazole, micafungin, caspofungin, terbinafine and 5-flucytosine) was determined via the microdilution broth method to determine the minimum inhibitory concentrations (MICs). Results A total of 75 cases of S. cerevisiae isolated from patients with vulvovaginal candidiasis (VVC, 44 cases), pneumonia (13 cases), or diarrhea (18 cases) were included after data review. The MICs of voriconazole and flucytosine for S. cerevisiae isolated from different body sites differed, with higher resistance in intestinal isolates. In this study, S. cerevisiae caused VVC, but there was no clear evidence that it was involved in pneumonia or diarrhea. Compared with those of Candida albicans, the primary pathogen of VVC, the MICs of fluconazole (11.96 ± 5.78 µg/mL vs. 67.64 ± 16.62 µg/mL, p = 0.002), itraconazole (0.77 ± 0.19 µg/mL vs. 2.31 ± 0.53 µg/mL, p = 0.008), voriconazole (0.22 ± 0.09 µg/mL vs. 5.02 ± 1.09 µg/mL, p

Abstract Background It is uncertain whether the weekend warrior pattern is associated with all-cause mortality among adults living with type 2 diabetes. This study explored how the ‘weekend warrior’ physical activity (PA) pattern was associated with all-cause mortality among adults living with type 2 diabetes. Methods This prospective cohort study investigated US adults living with type 2 diabetes in the National Health and Nutrition Examination Survey (NHANES). Mortality data was linked to the National Death Index. Based on self-reported leisure-time and occupational moderate-to-vigorous PA (MVPA), participants were categorized into 3 groups: physically inactive (

Abstract The combination of ASC22, an anti-PD-L1 antibody potentially enhancing HIV-specific immunity and chidamide, a HIV latency reversal agent, may serve as a strategy for antiretroviral therapy-free virological control for HIV. People living with HIV, having achieved virological suppression, were enrolled to receive ASC22 and chidamide treatment in addition to their antiretroviral therapy. Participants were monitored over 24 weeks to measure changes in viral dynamics and the function of HIV-specific CD8+ T cells (NCT05129189). 15 participants completed the study. At week 8, CA HIV RNA levels showed a significant increase from baseline, and the values returned to baseline after discontinuing ASC22 and chidamide. The total HIV DNA was only transiently increased at week 4 (P = 0.014). In contrast, integrated HIV DNA did not significantly differ from baseline. Increases in the proportions of effector memory CD4+ and CD8+ T cells (TEM) were observed from baseline to week 24 (P = 0.034 and P = 0.002, respectively). The combination treatment did not succeed in enhancing the function of HIV Gag/Pol- specific CD8+ T cells. Nevertheless, at week 8, a negative correlation was identified between the proportions of HIV Gag-specific TEM cells and alterations in integrated DNA in the T cell function improved group (P = 0.042 and P = 0.034, respectively). Nine adverse events were solicited, all of which were graded 1 and resolved spontaneously. The combined treatment of ASC22 and chidamide was demonstrated to be well-tolerated and effective in activating latent HIV reservoirs. Further investigations are warranted in the context of analytic treatment interruption.

Using Taraxacum kok-saghyz Rodin (TKS) roots as the raw material, the liquid-solid ratio, ultrasonic power, extraction temperature, and extraction time were selected as experimental factors. On the basis of single factor experiments, the response surface methodology was used to optimize the ultrasonic-assisted extraction process of polyphenols from the TKS roots. The in vitro antioxidant and hypoglycemic activity of the polyphenols extracted from TKS roots were measured. The results showed that the optimal extraction conditions were liquid-solid ratio of 33:1 mL/g, ultrasonic power of 270 W, extraction temperature of 61 ℃, and extraction time of 31 min. Under these conditions, the yield of polyphenols from TKS roots was 1.46%±0.03%. The in vitro activity test showed that the half inhibitory concentrations (IC50) of polyphenol extracts on DPPH and ABTS+ radicals were 54.06 and 39.27 µg/mL, respectively, the IC50 values for α-amylase and α-glucosidase were 133.26 and 50.22 µg/mL, respectively. This indicated that the polyphenols from TKS roots had strong antioxidant and hypoglycemic activities in vitro. This study can provide theoretical basis for the comprehensive development and utilization of TKS.

Marine unbonded flexible pipes serve as the most essential equipment in offshore oil and gas exploration and exploitation. Axial compressive loads during installation or in service in the complex marine environment usually lead to buckling failure. A flexible pipe is a composite structure with multiple functional layers, of which the tensile armor layer plays a key role with regard to the response of the pipe subjected to axial loads. In this paper, a simplified three-dimensional finite element model is developed, focusing on the tensile layer and replacing the carcass layer, pressure sheath layer, and pressure armor layer by a cylindrical rigid body to reduce computational expense. By using this model, the buckling failure modes of the tensile armor layer (in particular the birdcaging phenomenon) are analyzed. Several key parameters that affect the stability of the flexible pipe under axial compression and torsion are emphasized, and their effects on its axial and torsional stiffness are compared and discussed. The results show that both the lay angle of the steel wires and the interlayer friction coefficient have a significant influence on the axial and torsional stiffness of the pipe, whereas the damaged length of the outer sheath has virtually no effect.

The natural bone structure exhibits a radial gradient with dense cortical bone externally and porous cancellous bone internally. However, previous studies proposing scaffold designs have predominantly focused on homogeneous porous structures. Moreover, no consensus exists on the optimal structure for gradient porous scaffolds. Our scaffold closely imitated the natural bone structure by incorporating a gradient of pillar diameters. Additionally, we introduced a inverse gradient structure and three uniform diameter pillar structures (400 μm, 600 μm, and 1000 μm) for comparative analysis. Mechanical testing revealed that the compressive strength and elastic modulus of the Ti6Al4V porous scaffolds gradually increased with an increase in pillar diameter. In vitro experiments demonstrated that both the biomimetic gradient and inverse gradient scaffolds promoted osteogenic differentiation, with higher ALP activity (alkaline phosphatase) and osteogenesis-related gene expression compared to the uniform pillar structure scaffolds. The in vivo experiments confirmed these results, highlighting the superior ability of the biomimetic gradient Ti6Al4V porous scaffold to induce new bone formation. Based on our findings, we suggest that the optimal porous structure should have fine-diameter pillars (approximately 400 μm) internally to enhance cell penetration, while coarse-diameter pillars (approximately 800 μm) should be used externally to increase the cell attachment area and enhance mechanical strength. Overall, our study contributes to the field of bone tissue engineering by providing a biomimetic scaffold design that closely imitates the structure of natural bone and promotes osteogenic activity.

ObjectivesPyrophyllite, as a sealed pressure medium, has been widely used in high-pressure research for laboratories and industrial synthesis. A highly efficient pressure transfer medium can generate higher cell pressure at the same loading force. The use of a highly efficient pressure transfer medium reduces the risk of anvil rupture and production costs. Therefore, it is important to develop a suitable and efficient pressure-transmitting pyrophyllite.MethodsThe pressure calibration of four pyrophyllites from different localities at room temperature was conducted in a 6 × 8 MN multi-anvil large-volume press. The relationship between loading force and cell pressure at room temperature was established. The influence of mineral composition changes in pyrophyllite on pressure-transmitting efficiency was studied using X-ray diffraction.ResultsBy investigating the influence of mineral composition changes in pyrophyllite on pressure-transmitting efficiency, the results are as follows: (1) When achieving the same cell pressure, the required loading force for Pyrophyllite 4 is 10% lower than those for the other three pyrophyllites, indicating that Pyrophyllite 4 has the best pressure-transmitting efficiency. (2) As cell pressure increases, the relationship between cell pressure and loading force begins to deviate from linearity, and the pressure-transmitting efficiency of pyrophyllite gradually decreases. When the cell pressure exceeds 5.00 GPa, applying higher loading force does not significantly increase the cell pressure. (3) Higher hardness minerals (such as Diaspore, Boehmite) in pyrophyllite can effectively improve pressure-transmitting efficiency in the low-pressure stage (cell pressure 2.55-3.68 GPa). When the minerals in pyrophyllite undergo phase transformation to form new minerals with higher hardness (such as Muscovite and Kaolinite) in the high-pressure stage (cell pressure of 5.50 GPa), pressure-transmitting efficiency can be effectively improved.ConclusionsPyrophyllite 4 has better pressure-transmitting efficiency than Pyrophyllite 2 does in the high-pressure stage, but it is prone to failure in sealing due to the changes in mineral composition. However, Pyrophyllite 2 shows good elastic recovery effect and sealing performance and can stably complete compression and decompression work. Considering both pressure-transmitting efficiency and sealing effect, Pyrophyllite 2 has better application value and economic benefits.

Abstract Background Periodontal tissue loss is the main reason for tooth mobility and loss caused by periodontal disease. Dental follicle stem cells (DFSCs) have significant therapeutic potential in periodontal regeneration, which maybe mainly depends on their potent immunomodulatory capacity. Consequently, this study aims to elucidate the impact of implanted xenogenous DFSCs on innate immune responses during early and late stages in the periodontal defect repair period. Methods To trace and investigate the immunomodulation mechanisms of DFSCs in vivo, DFSCs were engineered (E-DFSCs) using lentiviral vectors expressing CD63-enhanced green fluorescent protein (CD63-EGFP) and β-Actin-mCherry protein (ACTB-mCherry) to exhibit green and red fluorescence. The biological characteristics and functions of E-DFSCs were verified by proliferation, differentiation, and co-culture experiments in vitro. In vivo, the periodontal regeneration capacity of E-DFSCs was detected by implantation of murine periodontal defect model, and the response of innate immune cells was detected at the 1st, 3rd, and 5th days (early stage) and 4th week (late stage) after implantation. Results In vitro assessments showed that E-DFSCs retain similar properties to their non-engineered counterparts but exhibit enhanced macrophage immunomodulation capability. In mice models, four-week micro-CT and histological evaluations indicated that E-DFSCs have equivalent efficiency to DFSCs in periodontal defect regeneration. At the early stage of repair in mice periodontal defect, fluorescence tracking showed that implanted E-DFSCs might primarily activate endogenous cells through direct contact and indirect actions, and most of these cells are myeloperoxidase-positive neutrophils. Additionally, compared with the control group, the neutrophilic infiltration and conversion of N2-type were significantly increased in the E-DFSC group. At the late stage of defect regeneration, more M2-type macrophages, fewer TRAP + osteoclasts, and an upregulated OPG/RANKL ratio were detected in the E-DFSC group compared to the control group, which indicated that immune balance tilts towards healing and bone formation. Conclusion The xenogenous implanted DFSCs can induce the N2 phenotype of neutrophils in the early stage, which can activate the innate immune mechanism of the host to promote periodontal tissue regeneration.

Abstract Purpose To summarize the abdominal computed tomography (CT) imaging and clinicopathological data of patients with SPNs of the pancreas and analyze the accuracy of preoperative CT diagnosis and features. Materials and methods Between June 2006 and June 2023, CT images of 120 histopathologically proven SPNs in the pancreas were retrospectively reviewed. Fifteen features, including age, sex, and CT-determined features, were included in a multiple stepwise regression analysis. The correlations between features and SPNs, including odds ratios (ORs) and 95% confidence intervals (CIs), were evaluated. Results Among the 120 patients, the diagnostic accuracy of CT was 43.3%. The baseline CT results of patients with a correct diagnosis and misdiagnosis revealed significant differences in sex (P = 0.043), age (P = 0.004), boundary (P = 0.037) and encapsulation (P = 0.002) between the two groups. The preoperative imaging diagnostic accuracy was significantly greater in females than in males (47.9% vs. 25.0%, P = 0.043). The immunohistochemical indices did not significantly differ between the two groups. The results of univariate analysis revealed significant differences in sex (P = 0.048), age (P = 0.014), tumor length (P = 0.023), tumor boundaries (P = 0.039) and capsule type (P = 0.003). The results of multivariate analysis revealed that encapsulation was closely related to the diagnostic accuracy of CT (P = 0.04). Conclusions The accuracy of CT in the diagnosis of SPNs is low, but a length‒diameter ratio of the tumor approaching 1.0, encapsulation and clear boundaries are important CT-determined features. The capsule is an independent CT predictor in the diagnosis of SPNs.

Abstract Backgroup The pathogenesis of shoulder impingement syndrome (SIS) is still unclear, and its questionable causal relationship with rotator cuff (RC) injury has led to confusion in treatment. The purpose of this study was to explore the bidirectional causal relationship between SIS and RC injury. Methods SIS and RC injury datasets downloaded from the IEU Open GWAS project and GWAS catalog databases. Inverse variance weighted (IVW), MR Egger, Weighted median, and Weighted mode were used in this Mendelian randomization (MR) analysis. Cochran’s Q test, leave-one-out, and funnel plot method were used to evaluate heterogeneity between single nucleotide polymorphisms (SNPs). MR-Egger regression was used to test the horizontal pleiotropy of this study. Results The IVW method (OR = 1.189, P = 0.0059) suggest the putative causal effect of RC injury on SIS. The results of MR Egger method (OR = 1.236, P = 0.2013), weighted median method (OR = 1.097, P = 0.2428) and weighted mode method (OR = 1.013, P = 0.930) showed no statistically significant (OR = 1.069071, P = 0.6173). Heterogeneity test and horizontal pleiotropy analysis suggested that there was no significant heterogeneity and horizontal pleiotropy in the results of this MR analysis. The reverse MR analysis showed heterogeneity, and the conclusion needs to be further explored. Conclusions The results of MR analysis support that RC injury may be causally associated with SIS.

Abstract Background The aim of this study was to describe our preliminary experience in the procedure of laparoscopic radical resection of hilar cholangiocarcinoma and to evaluate its feasibility, safety, and clinical efficacy. Methods A retrospective analysis was conducted on 44 patients with hilar cholangiocarcinoma who underwent laparoscopic surgery at our hospital from August 2019 to September 2023. Clinical data were collected from these patients, including 13 cases of Bismuth type I, 17 cases of Bismuth type II, 5 cases of Bismuth type IIIa, and 9 cases of Bismuth type IIIb. Results Laparoscopic radical resection of hilar cholangiocarcinoma was successfully performed in 38 patients (86.3%). Among the remaining patients, 3 required vascular reconstruction to complete radical surgery and were converted to laparotomies, while 3 others underwent T-tube drainage only due to unresectable metastases. The median operation time was 285 min (range, 190–450), and the median estimated blood loss was 360 mL (range, 260–1200). The postoperative hospital stay duration was 14.3 ± 3.6 days. No perioperative mortality was observed. Postoperative pathological examination revealed negative microscopic margins (R0) in 39 cases and positive microscopic margins (R1) in 2 cases. Postoperative complications occurred in 8 patients (18.1%), with 4 cases (9.0%) of Grade I, 3 cases (6.8%) of Grade II, 1 case (2.2%) of Grade IIIa, and no Grade IIIb or IV complications. The median overall survival for patients who underwent radical R0 resection was 30.4 months (range, 5.3–43.6). The Disease-free survival rates were 73.6% at 1 year, 61.2% at 2 years, and 40.1% at 3 years. Conclusion Total laparoscopic radical resection of hilar cholangiocarcinoma can be performed safely, feasibly, and effectively by experienced surgeons after an accurate preoperative evaluation.

Abstract Background Deep vein thrombosis (DVT) of lower extremity is a common complications after total knee arthroplasty (TKA). The purpose of this study was to evaluate the risk factors for DVT after TKA and analyze the expression of miR-199b-5p and nitric oxide (NO) before and after TKA, as well as their predictive value for DVT. Methods Basic clinical information of 121 patients with TKA was analyzed retrospectively. RT-qPCR was used to detect the relative expression level of miR-199b-5p in patients before and after TKA treatment. Based on the occurrence of DVT, patients were divided into DVT and non-DVT groups. Logistic regression analysis evaluated the risk factors of DVT. The receiver operating characteristic (ROC) curve assessed the predictive value of postoperative miR-199b-5p level, preoperative NO level, and their combination in DVT. The target genes of miR-199b-5p and their functions were predicted and annotated using bioinformatics analysis. Results The level of miR-199b-5p after TKA was upregulated compared with that before TKA (P

Abstract Background Glioblastoma (GB) is recognized as one of the most aggressive brain tumors, with a median survival of 14.6 months. However, there are still some patients whose survival time was greater than 3 years, and the biological reasons behind this clinical phenomenon arouse our research interests. By conducting proteomic analysis on tumor tissues obtained from GB patients who survived over 3 years compared to those who survived less than 1 year, we identified a significant upregulation of SelK in patients with shorter survival times. Therefore, we hypothesized that SelK may be an important indicator related to the occurrence and progression of GBM. Methods Proteomics and immunohistochemistry from GB patients were analyzed to investigate the correlation between SelK and clinical prognosis. Cellular phenotypes were evaluated by cell cycle analysis, cell viability assays, and xenograft models. Immunoblots and co-immunoprecipitation were conducted to verify SelK-mediated ubiquitin-dependent degradation of CDK4. Results SelK was found to be significantly upregulated in GB samples from short-term survivors (≤ 1 year) compared to those from long-term survivors (≥ 3 years), and its expression levels were negatively correlated with clinical prognosis. Knocking down of SelK expression reduced GB cell viability, induced G0/G1 phase arrest, and impaired the growth of transplanted glioma cells in nude mice. Down-regulation of SelK-induced ER stress leads to a reduction in the expression of SKP2 and an up-regulation of β-TrCP1 expression. Up-regulation of β-TrCP1, thereby accelerating the ubiquitin-dependent degradation of CDK4 and ultimately inhibiting the malignant proliferation of the GB cells. Conclusion This study discovered a significant increase in SelK expression in GB patients with poor prognosis, revealing a negative correlation between SelK expression and patient outcomes. Further mechanistic investigations revealed that SelK enhances the proliferation of GB cells by targeting the endoplasmic reticulum stress/SKP2/β-TrCP1/CDK4 axis.

Abstract Background Fatigue affects nurses negatively and may influence life satisfaction. According to the stress process model, active coping might influence the impact of adverse conditions such as fatigue on well-being measures such as life satisfaction. However, no research examined the associations among nurses’ fatigue, coping styles, and life satisfaction. Methods The cross-sectional study was conducted in Liaoning Province, China. 482 effective questionnaires were collected (effective response rate of 80.3%). The questionnaire included Fatigue Scale-14, Simplified Coping Style Questionnaire and Satisfaction with Life Scale. The association among fatigue, coping styles and fatigue × coping styles interaction with life satisfaction was examined by hierarchical multiple regression analysis. The interaction was visualized by simple slope analysis. Results Mean score of life satisfaction was 22.74 ± 6.11. Active coping moderated the relationship between mental fatigue and life satisfaction. The impacts of mental fatigue on life satisfaction gradually decreased in the low (1 SD below the mean, β=-0.400, P

Abstract Childhood leukemia is a prevalent form of pediatric cancer, with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) being the primary manifestations. Timely treatment has significantly enhanced survival rates for children with acute leukemia. This study aimed to develop an early and comprehensive predictor for hematologic malignancies in children by analyzing nutritional biomarkers, key leukemia indicators, and granulocytes in their blood. Using a machine learning algorithm and ten indices, the blood samples of 826 children with ALL and 255 children with AML were compared to a control group of 200 healthy children. The study revealed notable differences, including higher indicators in boys compared to girls and significant variations in most biochemical indicators between leukemia patients and healthy children. Employing a random forest model resulted in an area under the curve (AUC) of 0.950 for predicting leukemia subtypes and an AUC of 0.909 for forecasting AML. This research introduces an efficient diagnostic tool for early screening of childhood blood cancers and underscores the potential of artificial intelligence in modern healthcare.

Abstract CF2-containing compounds hold significant potential in drug discovery, organic synthesis, and materials science. However, synthesizing various CF2-containing building blocks from a single compound remains challenging. Here, we present a Cu-catalyzed, switchable defluoroborylation and hydrodefluorination of trifluoromethylated alkynes, yielding four types of CF2-containing compounds. The chemo- and regio-selective sp2/sp3 1,2-diborylation and sp2 monoborylation of 1-(trifluoromethyl)alkynes are controlled by adjusting the solvent and ligand quantity. Additionally, altering the base allows selective generation of gem-difluoroalkenes or difluoromethylalkenes. Notably, our method prevents over-defluorination of the CF3 group on unsaturated C-C bonds during nucleophilic additions, preserving the pharmaceutically valuable CF2 group. Experimental data and density functional theory (DFT) calculations elucidate the regioselectivities of Cu-Bpin addition and the regulatory role of the ligand in selective deborylation processes.

Abstract Mitochondrial RNA (mtRNA) in the cytosol can trigger the innate immune sensor MDA5, and autoinflammatory disease due to type I IFN. Here, we show that a dominant negative mutation in the gene encoding the mitochondrial exonuclease REXO2 may cause interferonopathy by triggering the MDA5 pathway. A patient characterized by this heterozygous de novo mutation (p.T132A) presented with persistent skin rash featuring hyperkeratosis, parakeratosis and acanthosis, with infiltration of lymphocytes and eosinophils around small blood vessels. In addition, circulating IgE levels and inflammatory cytokines, including IFNα, are found consistently elevated. Transcriptional analysis highlights a type I IFN gene signature in PBMC. Mechanistically, REXO2 (T132A) lacks the ability to cleave RNA and inhibits the activity of wild-type REXO2. This leads to an accumulation of mitochondrial dsRNA in the cytosol, which is recognized by MDA5, leading to the associated type I IFN gene signature. These results demonstrate that in the absence of appropriate regulation by REXO2, aberrant cellular nucleic acids may accumulate and continuously trigger innate sensors, resulting in an inborn error of immunity.

The impact of steaming time on the lipid oxidation and flavor of sturgeon dorsal meat were investigated. The study characterized the degree of lipid oxidation using peroxide value, acid value, malondialdehyde, and conjugated dienes. The effects of changes in fatty acid on volatile compounds and nutritional quality were examined and lipid profile was identified in a non-targeted metabolomics approach. Finally, an oxidation model was established to explore the specific effects of phospholipids on flavor formation. Results showed that the steaming sturgeon dorsal meat for 16 minutes resulted in moderate levels of lipid oxidation, which was conducive to the formation of characteristic flavors and high nutritional value due to the presence of abundant unsaturated fatty acids. The main unsaturated fatty acids found in association with phospholipids were linoleic acid (C18:2), docosahexaenoic acid (C22:6), oleic acid (C18:1), and arachidonic acid (C20:4), while the phospholipids were the primary precursors of volatile flavor compounds. Simulation of steaming conditions showed that the oxidation of phospholipids produced a large amount of pyrazine and furan compounds, providing roasted aromas for sturgeon dorsal meat steamed. In conclusion, moderate levels of lipid oxidation were beneficial for enhancing the flavor and nutritional quality of steamed sturgeon dorsal meat, and phospholipid oxidation had a significant impact on the formation of flavor. This study provides a theoretical basis for improving the flavor of sturgeon meat.

Introduction: Obesity has arisen as a prominent risk factor for COVID-19 severity and long COVID, potentially owed in part to the obesity-induced proinflammatory state. This study aimed to examine relationships among circulating inflammatory biomarkers and body mass index in nonhospitalized adults recently diagnosed with COVID-19. Methods: This analysis included participants who completed a randomized placebo-controlled trial conducted in October 2020–March 2021. Participants (19–53 years) were unvaccinated and enrolled following COVID-19 diagnosis as allowed by CDC return-to-work guidance. Anthropometrics and biomarkers were assessed at study baseline and week four. We examined the associations between body mass index (BMI) and inflammatory biomarkers via multiple regression models. Results: At study baseline (i.e., the point of enrollment following COVID-19 diagnosis) across all participants (N = 60), a higher BMI was associated with elevations in several inflammatory biomarkers including IL-6 (β = 7.63, 95% CI = 3.54, 11.89, p = 0.0004), ferritin (β = 6.31, 95% CI = 1.97, 10.83, p = 0.0047), high sensitivity C-reactive protein (β = 13.1, 95% CI = 8.03, 18.42, p = < 0.0001), tumor necrosis factor-α (β = 3.23, 95% CI = 0.91, 5.60, p = 0.0069), IL-12p40 (β = 3.69, 95% CI = 0.93, 6.52, p = 0.0094), IL-13 (β = 5.11, 95% CI = 1.00, 9.40, p = 0.0154), and IL-1Ra (β = 7.57, 95% CI = 3.61, 11.70, p = 0.0003). In control group participants (n = 30) after 4 weeks, a higher BMI was associated with elevations in IL-4 (β = 17.8, 95% CI = 0.84, 37.6, p = 0.0397) and sP-selectin (β = 1.16, 95% CI = 0.22, 2.11, p = 0.0182), controlling for baseline and covariates. Conclusions: Here, BMI was positively associated with circulating biomarkers of platelet activation and inflammation in adults recently diagnosed with COVID-19 after 4 weeks. The shift in post-acute COVID-19 inflammatory biomarkers associated with an increasing BMI noted here shares similarities to biomarkers of LC reported in the literature.

Abstract Purpose This study aimed to create and validate robust machine-learning-based prediction models for antipsychotic drug (risperidone) continuation in children and teenagers suffering from mania over one year and to discover potential variables for clinical treatment. Method The study population was collected from the national claims database in China. A total of 4,532 patients aged 4–18 who began risperidone therapy for mania between September 2013 and October 2019 were identified. The data were randomly divided into two datasets: training (80%) and testing (20%). Five regularly used machine learning methods were employed, in addition to the SuperLearner (SL) algorithm, to develop prediction models for the continuation of atypical antipsychotic therapy. The area under the receiver operating characteristic curve (AUC) with a 95% confidence interval (CI) was utilized. Results In terms of discrimination and robustness in predicting risperidone treatment continuation, the generalized linear model (GLM) performed the best (AUC: 0.823, 95% CI: 0.792–0.854, intercept near 0, slope close to 1.0). The SL model (AUC: 0.823, 95% CI: 0.791–0.853, intercept near 0, slope close to 1.0) also exhibited significant performance. Furthermore, the present findings emphasize the significance of several unique clinical and socioeconomic variables, such as the frequency of emergency room visits for nonmental health disorders. Conclusions The GLM and SL models provided accurate predictions regarding risperidone treatment continuation in children and adolescents with episodes of mania and hypomania. Consequently, applying prediction models in atypical antipsychotic medicine may aid in evidence-based decision-making.

AIM: To analyze the distribution of fibrovascular proliferative membranes (FVPMs) in proliferative diabetic retinopathy (PDR) patients that treated with pars plana vitrectomy (PPV), and to evaluate the outcomes separately. METHODS: This was a retrospective and cross-sectional study. Consecutive 25-gauge (25-G) PPV cases operated for PDR from May 2018 to April 2020. According to the FVPMs images outlined after operations, subjects were assigned into three groups: arcade type group, juxtapapillary type group, and central type group. All patients were followed up for over one year. General characteristics, operation-related variables, postoperative parameters and complications were recorded. RESULTS: Among 103 eyes recruited, the FVPMs distribution of nasotemporal and inferiosuperioral was significantly different (both P

Aiming at the specific operation path cruising problem of greenhouse tomato picking robots, this paper designs a laser SLAM (Simultaneous Localization And Mapping)-based autonomous navigation system for greenhouse tomato picking robots.The autonomous navigation system utilizes LiDAR to detect the greenhouse environment, creates an environment map with the Gmapping algorithm employing particle filtering, locates the robot with the AMCL (Adaptive Monte Carlo Localization) algorithm, devises the robot's path for picking tasks with the A* algorithm, and dynamically navigates around obstacles during operations with the DWA (Dynamic Window Approach) algorithm. The greenhouse experiment revealed that the robot's average deviance for both directions (X and Y) is 2.87 and 0.80 centimeters, respectively, when traveling a 320 centimeter path. On the other hand, its average variation across the directions of X and Y is 1.48 versus 1.08 centimeters when it passes through a 40 centimeter zone. The robot exhibits averaged variations of 1.73 and 2.24 millimeters in the X and Y axes, each, when navigating a 40-centimeter-radius turn. Furthermore, the robot exhibits average variations of 1.12 centimeters in the X and 0.78 centimeters in the Y directions when it follows a certain ''S''-shaped course. Based on the fulfillment of prescribed path cruising, the system has a high level of navigation and positioning accuracy, better meeting the requirements for greenhouse tomato harvesting robot direction and placement.

Gene transcription is an essential process involved in all aspects of cellular functions with significant impact on biological traits and diseases. This process is tightly regulated by multiple elements that co-operate to jointly modulate the transcription levels of target genes. To decipher the complicated regulatory network, we present a novel multi-view attention-based deep neural network that models the relationship between genetic, epigenetic, and transcriptional patterns and identifies co-operative regulatory elements (COREs). We applied this new method, named DeepCORE, to predict transcriptomes in various tissues and cell lines, which outperformed the state-of-the-art algorithms. Furthermore, DeepCORE contains an interpreter that extracts the attention values embedded in the deep neural network, maps the attended regions to putative regulatory elements, and infers COREs based on correlated attentions. The identified COREs are significantly enriched with known promoters and enhancers. Novel regulatory elements discovered by DeepCORE showed epigenetic signatures consistent with the status of histone modification marks.

Aims: The metabolic variations between the cartilage of osteoarthritis (OA) and Kashin-Beck disease (KBD) remain largely unknown. Our study aimed to address this by conducting a comparative analysis of the metabolic profiles present in the cartilage of KBD and OA. Methods: Cartilage samples from patients with KBD (n = 10) and patients with OA (n = 10) were collected during total knee arthroplasty surgery. An untargeted metabolomics approach using liquid chromatography coupled with mass spectrometry (LC-MS) was conducted to investigate the metabolomics profiles of KBD and OA. LC-MS raw data files were converted into mzXML format and then processed by the XCMS, CAMERA, and metaX toolbox implemented with R software. The online Kyoto Encyclopedia of Genes and Genomes (KEGG) database was used to annotate the metabolites by matching the exact molecular mass data of samples with those from the database. Results: A total of 807 ion features were identified for KBD and OA, including 577 positive (240 for upregulated and 337 for downregulated) and 230 negative (107 for upregulated and 123 for downregulated) ions. After annotation, LC-MS identified significant expressions of ten upregulated and eight downregulated second-level metabolites, and 183 upregulated and 162 downregulated first-level metabolites between KBD and OA. We identified differentially expressed second-level metabolites that are highly associated with cartilage damage, including dimethyl sulfoxide, uric acid, and betaine. These metabolites exist in sulphur metabolism, purine metabolism, and glycine, serine, and threonine metabolism. Conclusion: This comprehensive comparative analysis of metabolism in OA and KBD cartilage provides new evidence of differences in the pathogenetic mechanisms underlying cartilage damage in these two conditions. Cite this article: Bone Joint Res 2024;13(7):362–371.

Abstract Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by hyperglycemia resulting from defects in insulin secretion and/or insulin action. Increasing evidence suggests that inflammation played an important role in the pathogenesis of T2DM. Prospective studies on the link between immunoglobulins concentrations and the risk of T2DM in adults are limited. We developed a cohort study including 7,093 adults without T2DM history. The incidence of T2DM was 16.45 per 1,000 person-years. Compared with the lowest quartiles, the hazard ratios (95% confidence intervals) of T2DM for the highest quartiles of IgG, IgE, IgM and IgA were 0.64 (0.48–0.85), 0.94 (0.72–1.23), 0.68 (0.50–0.92) and 1.62 (1.24–2.11) (P for trend was

Abstract Asthma is a heterogeneous disease, and its development is the result of a combination of factors, including genetic factors, environmental factors, immune dysfunction and other factors. Its specific mechanism has not yet been fully investigated. With the improvement of disease models, research on the pathogenesis of asthma has made great progress. Immunological disorders play an important role in asthma. Previously, we thought that asthma was mainly caused by an imbalance between Th1 and Th2 immune responses, but this theory cannot fully explain the pathogenesis of asthma. Recent studies have shown that T-cell subsets such as Th1 cells, Th2 cells, Th17 cells, Tregs and their cytokines contribute to asthma through different mechanisms. For the purpose of the present study, asthma was classified into distinct phenotypes based on airway inflammatory cells, such as eosinophilic asthma, characterized by predominant eosinophil aggregates, and neutrophilic asthma, characterized by predominant neutrophil aggregates. This paper will examine the immune mechanisms underlying different types of asthma, and will utilize data from animal models and clinical studies targeting specific immune pathways to inform more precise treatments for this condition.

Abstract Peach tree is one of the most important fruit trees in the world, and it has been cultivated for more than 7,500 years. In recent years, the genome and population resequencing of peach trees have been published continuously, which has effectively promoted the research of peach tree genetics and breeding. In order to promote the further mining and utilization of these data, we integrated and constructed a comprehensive peach genome and variation database (PPGV, http://peachtree.work/home ). The PPGV contains 10 sets of published peach tree genome data, as well as genomic variation information for 1,378 peach tree samples (the resequencing data of 1,378 samples were aligned with the high-quality genomes of Lovell, CN14 and Chinesecling, respectively, for mutation detection). A variety of useful and flexible tools, such as BLAST, Gene ID Convert, KEGG/GO Enrichment, Primer Design and Gene function, were also specially designed for searching data and assisting in breeding.

Abstract Respiratory failure, intracranial hemorrhage and infection were more common in hyperleukocytic acute myeloid leukemia patients than in non-hyperleukocytic leukemia patients. Compared with non-apheresis treatment, the white blood cells decreased significantly and the infection rate decreased after apheresis treatment. However, the treatment time of leukapheresis in patients with hyperleukocytic leukemia is very long, while it is more damaging to cells. In this study, which conducted a retrospective analysis on patients with hyperleukocytic acute myeloid leukemia, the process of centrifugation of normal cells and patients’ cells by apheresis machine was simulated in vitro. Through selecting 5 healthy persons and 11 patients with hyperleukocytic acute myeloid leukemia, extracting their blood samples and performing in vitro centrifugation at different speeds or duration, we observed the changes of the numbers and morphology of peripheral blood cells in healthy people and patients, so as to explore the optimal centrifugation parameters during leukapheresis. The cells obtained by the optimal centrifugation parameters were cryopreserved and two groups of mice (10 mice in each group) were used to establish leukemia animal models. Through the research, it is found that when the centrifugal speed is below 6000 rpm, the damage to blood cells in healthy people and in patients with hyperleukocytic leukemia is not obvious. When the centrifugal speed is above 6000 rpm, the platelets will be damaged significantly. The cells obtained under the optimal centrifugation parameters can be successfully cryopreserved and used to establish leukemia animal models. This study is of great significance for improving the efficiency and reducing the side effects of leukapheresis, and is helpful to improve the treatment of white blood cells reduction.

Abstract In recent decades, the atmospheric moisture capacity has increased globally in concert with global warming, with a particularly notable warming trend in Arctic regions. However, due to limited observational data, the variation and causes of polar precipitation, especially large-scale precipitation events associated with Arctic cyclones, remain unclear. In this paper, GPM satellite data are compared with ERA5 reanalysis data to explore the characteristics of summer precipitation at the northern margin of the Eurasian region (NMER) and the influence of cyclone activity on precipitation. It is revealed that high precipitation values in the Arctic region, as indicated by the GPM and ERA5 data, are mainly concentrated at the NMER. However, the GPM data show an overall larger precipitation amount, while the station observations more closely agree with the ERA5 precipitation changes at the NMER. The cyclone identification results indicate that summer cyclones at the NMER are mainly distributed in the Barents, Kara and Laptev Seas, and the precipitation contribution rate of ERA5-derived cyclones is 37.35%, which is significantly higher than that of GPM-derived cyclones (29.47%). Furthermore, high cyclone activity results in more intense precipitation, with the top 5% of the strongest cyclones contributing 60% (GPM) and 40% (ERA5) to the total cyclonic precipitation.

Abstract With the development of science and technology and economy, UAV is used more and more widely. However, the existing UAV trajectory planning methods have the limitations of high cost and low intelligence. In view of this, grey Wolf algorithm is being used to achieve collaborative trajectory optimization of UAV groups. However, it is found that the Grey Wolf optimization algorithm (GWO) has the problem of weak cooperation. In this study, based on the traditional GWO pheromone factor is introduced to improve it.. Aiming at the problem of unstable performance of swarm intelligence optimization algorithm under dynamic threat, deep reinforcement learning is used to optimize the model. An unmanned aerial vehicle swarm trajectory planning model was constructed based on the improved grey wolf algorithm. Through experimental analysis, the optimal fitness value of the improved grey wolf algorithm was lower than 0.43 of the grey wolf algorithm. Compared with other algorithms, the fitness value of this algorithm is significantly reduced and the stability is higher. In complex scenarios, the improved grey wolf algorithm had a trajectory length of 70.51 km and a planning time of 5.92 s, which was clearly superior to other algorithms. The path length planned by the research and design model was 58.476 km, which was significantly smaller than the other three models. The planning time was 5.33 s and the number of path extension points was 46. The indicator values of the Unmanned Aerial Vehicle swarm trajectory planning model designed by this research were all smaller than the other three models. By analyzing the results, the model can achieve low-cost trajectory optimization, providing more reasonable technical support for unmanned aerial vehicle mission execution.

Abstract During the treatment of 89 pediatric patients with Acute Myeloid Leukemia (AML) at the Hematology Department of Kunming Medical University’s Children’s Hospital from 2020 to 2023, three patients were identified to co-express the NUP98-NSD1, FLT3-ITD, and WT1 gene mutations. The bone marrow of these three patients was screened for high-risk genetic mutations using NGS and qPCR at the time of diagnosis. The treatment was administered following the China Children’s Leukemia Group (CCLG)-AML-2019 protocol. All three patients exhibited a fusion of the NUP98 exon 12 with the NSD1 exon 6 and co-expressed the FLT3-ITD and WT1 mutations; two of the patients displayed normal karyotypes, while one presented chromosomal abnormalities. During the induction phase of the CCLG-AML-2019 treatment protocol, the DAH (Daunorubicin, Cytarabine, and Homoharringtonine) and IAH (Idarubicin, Cytarabine, and Homoharringtonine) regimens, in conjunction with targeted drug therapy, did not achieve remission. Subsequently, the patients were shifted to the relapsed/refractory chemotherapy regimen C + HAG (Cladribine, Homoharringtonine, Cytarabine, and G-CSF) for two cycles, which also failed to induce remission. One patient underwent Haploidentical Hematopoietic Stem Cell Transplantation (Haplo-HSCT) and achieved complete molecular remission during a 12-month follow-up period. Regrettably, the other two patients, who did not receive transplantation, passed away. The therapeutic conclusion is that pediatric AML patients with the aforementioned co-expression do not respond to chemotherapy. Non-remission transplantation, supplemented with tailor-made pre- and post-transplant strategies, may enhance treatment outcomes.

Mycena (Pers.) Roussel (1806) is a large genus of Mycenaceae known for having small to medium-sized basidiomata. It is typified by the species Mycena galericulata (Scop.) Gray. For years, many mycologists have made important contributions to understanding Mycena and several monographs have been published. Three specimens were collected from China that belonged to the genus Mycena. On the basis of morphological analysis and phylogenetic analyses employing DNA sequences, a new species is described.Mycena brunnescens sp. nov. is described as a new species from subtropical areas of China. It is characterised by its brown pileus, whitish lamellae that turns brown when bruised, orange to brown lamellae edges, the absence of pleurocystidia and cheilocystidia with simple or branched excrescences at the apex containing yellowish-brown contents. We performed phylogenetic analyses on a concatenated dataset comprising the internal transcribed spacer and large subunit regions of nuclear ribosomal RNA using Bayesian Inference and Maximum Likelihood methods. The result showed that the new taxon clustered in an independent group and is closely related to M. albiceps and M. flosoides.

Abstract Background Although the inherited risk factors associated with fatty liver disease are well understood, little is known about the genetic background of metabolic dysfunction-associated steatotic liver disease (MASLD) and its related health impacts. Compared to non-alcoholic fatty liver disease (NAFLD), MASLD presents significantly distinct diagnostic criteria, and epidemiological and clinical features, but the related genetic variants are yet to be investigated. Therefore, we conducted this study to assess the genetic background of MASLD and interactions between MASLD-related genetic variants and metabolism-related outcomes. Methods Participants from the UK Biobank were grouped into discovery and replication cohorts for an MASLD genome-wide association study (GWAS), and base and target cohorts for polygenic risk score (PRS) analysis. Autosomal genetic variants associated with NAFLD were compared with the MASLD GWAS results. Kaplan–Meier and Cox regression analyses were used to assess associations between MASLD and metabolism-related outcomes. Results Sixteen single-nucleotide polymorphisms (SNPs) were identified at genome-wide significance levels for MASLD and duplicated in the replication cohort. Differences were found after comparing these SNPs with the results of NAFLD-related genetic variants. MASLD cases with high PRS had a multivariate-adjusted hazard ratio of 3.15 (95% confidence interval, 2.54–3.90) for severe liver disease (SLD), and 2.81 (2.60–3.03) for type 2 diabetes mellitus. The high PRS amplified the impact of MASLD on SLD and extrahepatic outcomes. Conclusions High PRS of MASLD GWAS amplified the impact of MASLD on SLD and metabolism-related outcomes, thereby refining the process of identification of individuals at high risk of MASLD. Supplementation of this process with relevant genetic backgrounds may lead to more effective MASLD prevention and management.

Abstract Background Infertility produces infertility-related stress in both members of infertile couples, especially for infertile women. Some studies verified the negative relationship between infertility-related stress and outcomes of infertility treatments. Effective mental health care during fertility treatment is urgently needed, but there has been a lack of efficient support services. To reduce the infertility-related stress of infertile women, expressive art therapeutic schemes will be organized and implemented by certified international expressive art therapists. Methods This study is a randomized controlled trial. Participants in the intervention group will receive expressive art therapies after the baseline investigation. Expressive art therapies will be led by the certified international expressive art therapist. The interventions include progressive muscle relaxation training, music meditation and drawing therapy. Participants in the control group will receive routine care. The Hospital Anxiety and Depression Scale (HADS) and Fertility Problem Inventory (FPI) will be used to investigate the anxiety, depression, and infertility-related stress of all participants at admission and at discharge. Discussion This study will verify the effectiveness and efficiency of expressive art therapies for infertile women. The results will provide new knowledge on mental health care strategies for infertile women. Trial registration ChiCTR, ChiCTR2300070618. Registered 14 April 2023.

Abstract Background Carotid artery stenosis (CAS) is a major cause of cerebral ischemic events (CIE). The purpose of the research was to reveal the diagnostic accuracy of long non-coding RNA hox transcript antisense intergenic RNA (HOTAIR) in asymptomatic carotid artery stenosis (ACAS) patients and its predictive significance in CIE incidence. Methods 88 patients with ACAS and 80 controls were included. Blood samples were collected and serum HOTAIR levels were detected by qRT-PCR. Logistic regression examined factors associated with the degree of carotid stenosis. The receiver operating characteristic (ROC) curve assessed the diagnostic accuracy of HOTAIR in identifying patients with ACAS. Predictive value of serum HOTAIR levels for the occurrence of CIE was assessed by Kaplan–Meier curves and Cox regression. Results Serum HOTAIR was markedly lower in ACAS patients than in controls (P

Abstract The OVATE gene family plays an important role in regulating the development of plant organs and resisting stress, but its expression characteristics and functions in sorghum have not been revealed. In this study, we identified 26 OVATE genes in the sorghum BTx623 genome, which were divided into four groups and distributed unevenly across 9 chromosomes. Evolutionary analysis showed that after differentiation between sorghum and Arabidopsis, the OVATE gene family may have experienced unique expansion events, and all OVATE family members were negatively selected. Transcriptome sequencing and RT-qPCR results showed that OVATE genes in sorghum showed diverse expression characteristics, such as gene SORBl_3001G468900 and SORBl_3009G173400 were significantly expressed in seeds, while SORBI_3005G042700 and SORBI_3002G417700 were only highly expressed in L1. Meantime, in the promoter region, a large number of hormone-associated cis-acting elements were identified, and these results suggest that members of the OVATE gene family may be involved in regulating specific development of sorghum leaves and seeds. This study improves the understanding of the OVATE gene family of sorghum and provides important clues for further exploration of the function of the OVATE gene family.

Abstract Myelodysplastic syndromes (MDS) are clonal hematopoietic malignancies and seriously threaten people’s health. Current therapies include bone marrow transplantation and several hypomethylating agents. However, many elderly patients cannot benefit from bone marrow transplantation and many patients develop drug resistance to hypomethylating agents, making it urgent to explore novel therapy. RSL3 can effectively induce ferroptosis in various tumors and combination of RSL3 and hypomethylating agents is promising to treat many tumors. However, its effect in MDS was unknown. In this study, we found that RSL3 inhibited MDS cell proliferation through inducing ROS-dependent apoptosis. RSL3 inhibited Bcl-2 expression and increased caspase 3 and PARP cleavage. RNA-seq analysis revealed that MYB may be a potential target of RSL3. Rescue experiments showed that overexpression of MYB can rescue MDS cell proliferation inhibition caused by RSL3. Cellular thermal shift assay showed that RSL3 binds to MYB to exert its function. Furthermore, RSL3 inhibited tumor growth and decreased MYB and Bcl-2 expression in vivo. More importantly, RSL3 decreased the viability of bone marrow mononuclear cells (BMMCs) isolated from MDS patients, and RSL3 had a synergistic effect with DAC in MDS cells. Our studies have uncovered RSL3 as a promising compound and MYB/Bcl-2 signaling pathway as a potential target for MDS treatment.

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