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For improving the dynamic management performance of construction cost, the dynamic control model of cost of construction based on fuzzy neural network is studied. Consider the effect of resource allocation, construction progress and construction quality on the cost of project in construction stage, and build the cost control index for the project in stage of construction. The fuzzy logic model is used in selecting the main cost related indicators from project cost control index system at the construction stage as input neurons of the BP NN, and the BP neural network is employed to output the results of prediction of cost at the construction stage. The project cost prediction results are set as the data basis for the dynamic control of the project cost, determine the most optimistic cost, the most probable cost and the most pessimistic cost of project cost in stage of construction through key chain method, and set buffers to realize dynamic control of project cost in stages of construction. The evaluation results prove that the developed method will be able to accurately predict the project cost in stages of construction, and the cost saved in the construction phase of the project is more than 300000 yuan.

Abstract The pursuit of innovative therapeutic strategies in oncology remains imperative, given the persistent global impact of cancer as a leading cause of mortality. Immunotherapy is regarded as one of the most promising techniques for systemic cancer therapies among the several therapeutic options available. Nevertheless, limited immune response rates and immune resistance urge us on an augmentation for therapeutic efficacy rather than sticking to conventional approaches. Ferroptosis, a novel reprogrammed cell death, is tightly correlated with the tumor immune environment and interferes with cancer progression. Highly mutant or metastasis-prone tumor cells are more susceptible to iron-dependent nonapoptotic cell death. Consequently, ferroptosis-induction therapies hold the promise of overcoming resistance to conventional treatments. The most prevalent post-transcriptional modification, RNA m6A modification, regulates the metabolic processes of targeted RNAs and is involved in numerous physiological and pathological processes. Aberrant m6A modification influences cell susceptibility to ferroptosis, as well as the expression of immune checkpoints. Clarifying the regulation of m6A modification on ferroptosis and its significance in tumor cell response will provide a distinct method for finding potential targets to enhance the effectiveness of immunotherapy. In this review, we comprehensively summarized regulatory characteristics of RNA m6A modification on ferroptosis and discussed the role of RNA m6A-mediated ferroptosis on immunotherapy, aiming to enhance the effectiveness of ferroptosis-sensitive immunotherapy as a treatment for immune-resistant malignancies.

Abstract Stereotactic radiation therapy (SBRT) has emerged as a promising treatment modality for locally advanced pancreatic cancer. The aim of this study is to assess the dosimetric efficacy of online adaptive radiotherapy (ART) in comparison to image-guided radiation therapy (IGRT) for pancreatic cancer. We conducted a retrospective analysis involving 8 patients diagnosed with locally advanced pancreatic cancer. The gross tumor volume (GTV) delineates the visible extent of the tumor on imaging, while the planning tumor volume (PTV) was generated by expanding 5 mm from the GTV and ensuring a 3 mm distance from the small intestine, duodenum, and stomach simultaneously. Treatment planning was executed using the United Imaging Healthcare Treatment Planning System workstation. The control group underwent evaluation based on daily validated fan-beam CT (FBCT) scans, assessing both the dose delivered to actual organs at risk (OARs) and the target volume. Radiotherapy plans were developed utilizing simulation CT, and conventional radiotherapy with daily image-guided radiation therapy (IGRT) was administered using FBCT-Linac. Conversely, patients in the study group received daily validated FBCT-guided adaptive radiotherapy plans, with a focus on mean dose assessment of both the target volume and OARs. Subsequently, we compared the average outcomes of each treatment fraction between IGRT and online adaptive radiotherapy (ART). Comparison between ART and IGRT treatment plans revealed significant differences in various dosimetric parameters: For PTV: V98%: ART (96.28%) vs IGRT (89.73%), p = 0.000, V95%: ART (96.28%) vs IGRT (89.73%), p = 0.031, V90%: ART (98.58%) vs IGRT (93.65%), p = 0.000, Dmean: ART (4912.91) vs IGRT (4804.11), p = 0.000. For GTV: V100%: ART (97.96%) vs IGRT (94.85%), p = 0.314, V98%: ART (100.00%) vs IGRT (96.83%), p = 0.000, V90%: ART (100.00%) vs IGRT (97.75%), p = 0.000, Dmean: ART (4972.17) vs IGRT (4907.23), p = 0.000. For the duodenum: D0.5cc: ART (2883.92) vs IGRT (3359.35), p = 0.000, D1cc: ART (2726.32) vs IGRT (3128.66), p = 0.001, D5cc: ART (2051.96) vs IGRT (2273.93), p = 0.015, D10cc: ART (1650.73) vs IGRT (1731.74), p = 0.211. For the small bowel: D0.5cc: ART (3022.3) vs IGRT (3142.64), p = 0.037. D5cc: ART (2151.09) vs IGRT (2389.15), p = 0.043, D10cc: ART (1775.20) vs IGRT (1942.00), p = 0.079. For the stomach: D0.5cc: ART (3353.92) vs IGRT (4117.85), p = 0.000, D5cc: ART (2860.20) vs IGRT (3235.41), p = 0.000, D10cc: ART (2553.72) vs IGRT (2836.73), p = 0.000. For the Dmean of the left kidney and right kidney: Left kidney: ART (248.28) vs IGRT (239.65), p = 0.100. Right kidney: ART (314.55) vs IGRT (307.17), p = 0.345. These results suggest significant improvements in PTV coverage and sparing of OARs with ART compared to IGRT, indicating the potential of ART in optimizing treatment outcomes for pancreatic cancer patients. Compared to conventional IGRT-guided SBRT programs, ART-based SBRT for pancreatic cancer not only enhances the dose distribution to the target volume but also mitigates the radiation exposure to critical organs-at-risk (OARs) such as the duodenum, small intestine, and stomach. This approach may offer a more favorable safety profile while concurrently enhancing treatment efficacy.

Abstract High-grade B-cell lymphoma with 11q aberration (HGBL-11q) is a distinct lymphoma entity according to the 5th edition of the WHO classification of hematolymphoid tumors. It lacks MYC translocation but carries proximal gains and/or telomeric losses of chromosome 11q. This rare type of B-cell lymphoma is less frequently reported in people living with HIV (PLWH), and its exact frequency remains unclear. Our goal was to retrospectively analyze its frequency in a cohort of aggressive B-cell lymphomas in PLWH, including Burkitt lymphoma (BL, n = 35), diffuse large B-cell lymphoma (DLBCL, n = 48), high-grade B-cell lymphoma, not otherwise specified (HGBL-NOS, n = 13), which was diagnosed as AIDS-related lymphoma (ARL) at our institution. In total, 10/96 (10.4%) cases harbored the typical 11q aberration pattern, predominantly those that had been classified as BL (6/35, 17.1%), DLBCL (2/48, 4.2%), and HGBL, NOS (2/13, 15.4%). We also evaluated 7 cases of AIDS-related HGBL-11q (AR-HGBL-11q) reported in the literature. The median age of our cohort was 35 years, and all the patients were male. Most cases (70%) had a history of HIV infection for over 1 year, and all were involved in lymph nodes (100%), frequently involved extranodal sites (60%), and Ann Arbor stage III/IV. In histomorphology, the cases exhibited diverse cytological features, reminiscent of BL (6 cases), DLBCL (2 cases), and HGBL (2 cases). A comparison of the combined cohort of 17 AR-HGBL-11q cases with 11 ARL cases that lacked both MYC rearrangement and 11q aberration at our institution showed that HGBL-11q cases were characterized by strikingly coarse apoptotic debris (P

Abstract Ginsenoside Rb1 exhibits a wide range of biological activities, and gut microbiota is considered the main metabolic site for Rb1. However, the impact of gut microbiota on the pharmacokinetics of Rb1 are still uncertain. In this study, we investigated the gut microbiome changes and the pharmacokinetics after a 30 d Rb1 intervention. Results reveal that the systemic exposure and metabolic clearance rate of Rb1 and Rd were substantially affected after orally supplementing Rb1 (60 mg/kg) to rats. Significant increase in the relative abundance of Bacteroides cellulosilyticus in gut microbiota and specific glycoside hydrolase (GH) families, such as GH2, GH92, and GH20 were observed based on microbiome and metagenomic analysis. Moreover, a robust association was identified between the pharmacokinetic parameters of Rb1 and the relative abundance of specific Bacteroides species, and glycoside hydrolase families. Our study demonstrates that Rb1 administration significantly affects the gut microbiome, revealing a complex relationship between B. cellulosilyticus, key GH families, and Rb1 pharmacokinetics.

Abstract Background The association between red blood cell distribution width (RDW) to albumin ratio (RAR) and prognosis in patients with acute respiratory failure (ARF) admitted to the Intensive Care Unit (ICU) remains unclear. This retrospective cohort study aims to investigate this association. Methods Clinical information of ARF patients was collected from the Medical Information Mart for Intensive Care IV (MIMIC-IV) version 2.0 database. The primary outcome was, in-hospital mortality and secondary outcomes included 28-day mortality, 60-day mortality, length of hospital stay, and length of ICU stay. Cox regression models and subgroup analyses were conducted to explore the relationship between RAR and mortality. Results A total of 4547 patients with acute respiratory failure were enrolled, with 2277 in the low ratio group (RAR = 4.83). Kaplan-Meier survival analysis demonstrated a significant difference in survival probability between the two groups. After adjusting for confounding factors, the Cox regression analysis showed that the high RAR ratio had a higher hazard ratio (HR) for in-hospital mortality (HR 1.22, 95% CI 1.07–1.40; P = 0.003), as well as for 28-day mortality and 60-day mortality. Propensity score-matched (PSM) analysis further supported the finding that high RAR was an independent risk factor for ARF. Conclusion This study reveals that RAR is an independent risk factor for poor clinical prognosis in patients with ARF admitted to the ICU. Higher RAR levels were associated with increased in-hospital, 28-day and 60-day mortality rates.

Abstract Background Accumulating evidence shows that free fatty acids (FFA) are associated with gestational diabetes mellitus (GDM). However, most of the studies focus on a few specific types of FFA, such as α-linolenic acid (C18:3n3) and Arachidonic acid (C20:4n6) or a total level of FFA. Objective This study aimed to test the association between a variety of FFAs during the first trimester and the risk of GDM. Methods The participants came from the Zhoushan Pregnant Women Cohort (ZWPC). A 1:2 nested case-control study was conducted: fifty mothers with GDM were matched with 100 mothers without GDM by age, pre-pregnancy body mass index (BMI), month of oral glucose tolerance test (OGTT) and parity. Thirty-seven FFAs (including 17 saturated fatty acids (SFA), 8 monounsaturated fatty acids (MUFA), 10 polyunsaturated fatty acids (PUFA) and 2 trans fatty acids (TFA)) in maternal plasma during the first trimester were tested by Gas Chromatography–Mass Spectrometry (GC-MS). Conditional logistic regression models were performed to assess the associations of FFA with the risk of GDM. Results Nine FFAs were respectively associated with an increased risk of GDM (P

Abstract Background High-density lipoprotein cholesterol (HDL-C) is widely recognized for its protective effects against cognitive decline. However, recent studies have presented conflicting results, with some suggesting no significant cognitive benefits or even an increased risk of dementia associated with high HDL-C levels. For those who suffer from depression, the cognitive benefits of HDL-C may be diminished or reversed. The purpose of this study is to investigate the associations between HDL-C, cognitive ability, and depressive symptoms in middle-aged and older Chinese adults. Methods The datasets utilized were sourced from the China Health and Retirement Longitudinal Study (CHARLS) for the years 2011 and 2015, comprising 4,302 participants. Cross-lagged models were employed to explore the temporal sequence between cognitive performance and HDL-C levels, and to examine the interplay among depression, cognition, and HDL-C. Confounding factors such as sociodemographic characteristics, sleep conditions, and history of chronic diseases were controlled for. Results The analysis revealed unidirectional effects of baseline impaired cognition and greater severity of depression on increased HDL-C levels at follow-up (β = − 0.036 and β = 0.028, respectively, P 0.05). Depressive symptoms and cognition were found to have a significant bidirectional association (β = − 0.026 and β = − 0.053, respectively, P

Thyroid storm is a rare but life-threatening condition mainly triggered by infection and abrupt discontinuation of antithyroid drug therapy for Graves’ disease. Pancytopenia is a rare adverse reaction to antithyroid drugs. We present a 13-year-old girl with thyroid storm and pancytopenia with symptoms similar to those of methimazole-induced pancytopenia. Although in this context the use of methimazole is still under debate, due to multiple normal complete blood counts (CBC) monitored during fever, sepsis-induced pancytopenia with thyroid storm was considered, and methimazole treatment combined with methylprednisolone and meropenem was able to resolve both pancytopenia and thyroid storm. During the period of infection and antithyroid drug therapy, close monitoring of CBC may help differentiate the aetiology of pancytopenia. This is the first paediatric case report that outlines the use of methimazole in the management of thyroid storm with pancytopenia.

Abstract Background The study assessed the association between COVID-19 and new-onset obstructive airway diseases, including asthma, chronic obstructive pulmonary disease, and bronchiectasis among vaccinated individuals recovering from COVID-19 during the Omicron wave. Methods This multicenter retrospective cohort study comprised 549,606 individuals from the U.S. Collaborative Network of TriNetX database, from January 8, 2022, to January 17, 2024. The hazard of new-onset obstructive airway diseases between COVID-19 and no-COVID-19 groups were compared following propensity score matching using the Kaplan–Meier method and Cox proportional hazards model. Results After propensity score matching, each group contained 274,803 participants. Patients with COVID-19 exhibited a higher risk of developing new-onset asthma than that of individuals without COVID-19 (adjusted hazard ratio (aHR), 1.27; 95% CI, 1.22–1.33; p

Abstract Background This study aimed to establish a consensus on the delineation of target volumes for neoadjuvant radiation therapy (nRT) in esophageal squamous cell carcinoma (ESCC) within China. Methods From February 2020 to June 2021, nine ESCC patients who received nRT were retrospectively selected from Sun Yat-sen University Cancer Center and Shandong Cancer Hospital. A panel from eight cancer radiotherapy centers performed two rounds of nRT target volume delineation for these patients: the first round for cases 1–6 and the second for cases 7–9. Online meetings were held after each delineation round to discuss findings. The consistency of delineations across centers was compared using mean undirected Hausdorff distances (Hmean), dice similarity coefficients (DSC), and total volumes, analyzed with the Mann-Whitney U test. Results The second round of delineations showed improved consistency across centers (total clinical target volume (CTVtotal): mean DSC = 0.76–0.81; mean Hmean = 2.11–3.14 cm) compared to the first round (CTVtotal: mean DSC = 0.63–0.64; mean Hmean = 5.66–7.34 cm; DSC and Hmean: P

Abstract Background Central obesity was considered as a risk factor for falls among the older population. Waist circumference (WC), lipid accumulation product (LAP), visceral adiposity index (VAI), and the Chinese visceral adiposity index (CVAI) are considered as surrogate markers for abdominal fat deposition in increasing studies. Nevertheless, the longitudinal relationship between these indices and falls among the older population remains indistinct. This study aimed to explore the association between abdominal obesity indices and falls among older community-dwellers. Methods Our study included 3501 individuals aged ≥ 65 years from the Guangzhou Falls and Health Status Tracking Cohort at baseline in 2021 and then prospectively followed up in 2022. The outcome of interest was the occurrence of falls. The Kaplan-Meier curves and multivariable Cox regression analysis were used to explore the associations between abdominal obesity indices and falls. Moreover, the restricted cubic spline analysis (RCS) was conducted to test the non-linear relationships between abdominal obesity indices and hazards of falls incident. Results After a median follow-up period of 551 days, a total of 1022 participants experienced falls. The cumulative incidence rate of falls was observed to be higher among individuals with central obesity and those falling within the fourth quartile (Q4) of LAP, VAI, and CVAI. Participants with central obesity and those in Q4 of LAP, VAI, and CVAI were associated with higher risk of falls, with hazard ratios (HRs) of 1.422 (HR 95%CI: 1.255–1.611), 1.346 (1.176–1.541), 1.270 (1.108–1.457), 1.322 (1.154–1.514), respectively. Each 1-SD increment in WC, LAP, VAI, and CVAI was a significant increased risk of falls among participants. Subgroup analysis further revealed these results were basically stable and appeared to be significantly stronger among those females, aged 65–69 years, and with body mass index (BMI) ≥ 28 kg/m2. Additionally, RCS curves showed an overall upward trend in the risk of falls as the abdominal indices increased. Conclusions Abdominal obesity indices, as WC, LAP, VAI, and CVAI were significantly associated with falls among older community-dwellers. Reduction of abdominal obesity indices might be suggested as the strategy of falls prevention.

Purpose: The purpose of our study is to explore the influence of Metaverse on FinTech industry and identify the mediators between them. Design/methodology/approach: To achieve the purpose, we conducted words frequency analysis, network analysis, and association rules analysis, based on 68,957 Metaverse-related and 23,902 FinTech-related news articles from January 1, 2021, to September 31, 2023. Findings: The results from the analysis indicate that the five most frequently shown words are 'Metaverse', 'Fintech', 'Technology', 'Investment', and 'Platform'. Additionally, the outcomes of association rules analysis highlight relationships between the Metaverse and FinTech through terms like 'Service', 'Platform', 'Digital' and 'Information'. Research limitations/implications: Our findings emphasize the crucial significance of Metaverse in FinTech Industry, providing insights for related investors or stakeholders. The reliance on news data only may have constrained the depth of insights ion the dynamics between the Metaverse and FinTech, thereby future study could benefit from video content, industry reports or white papers. Originality/value: While many studies on the Metaverse and FinTech focus on exploratory or theoretical discussions, this study performed an in-depth textual analysis of the collected text data on these topics. This study not only provides understanding of the relationship between the Metaverse and FinTech but also suggests future applications in other fields.

Abstract Lightweight thin-walled parts are widely used in the aviation and aerospace industries, and with the further increase in the complexity of their features, the traditional manufacturing process can no longer fully meet the high requirements of industrial component manufacturing. In this work, thin-walled parts are processed by Laser based powder bed fusion of metals (PBF-LB/M), and the effects of process parameters on residual stress, hardness, mechanical properties and microstructure of thin-walled parts are systematically investigated. The simulation results show that the maximum equivalent residual stresses are distributed in the combination of the solid and the substrate, and the minimum equivalent residual stresses are mainly distributed in the top two ends and the middle part of the solid, and the stress distribution is symmetrical. In addition, the maximum equivalent residual stress increases with the increase of laser power, and decreases with the increase of scanning spacing or scanning speed. The experimental results show that with the increase of laser energy density, the tensile strength and yield strength of thin-walled parts show a tendency of increasing first and then decreasing. Finally, high-quality thin-walled parts were successfully fabricated by the optimized process parameters, and their tensile and yield strengths were increased by 6.1% and 15.9%, respectively.

Abstract Background Several studies have demonstrated that older adults with type 2 diabetes mellitus (T2DM) have a higher risk of falls compared to those without T2DM, which may lead to disability and a lower quality of life. While, limited prospective studies have quantified the associations in southern China. We conducted a longitudinal cohort study to quantify the associations between T2DM and falls and investigate the risk factors of falls among community-dwelling elderly people in Guangzhou, China. Methods The population-based study included 8800 residents aged 65 and over in 11 counties of Guangzhou at baseline in 2020 and then prospectively followed up through 2022. Of 6169 participants had complete follow-up and were included in the present study. A fall event was identified by self-reported. The Cox regression was applied to quantify the associations between T2DM and falls, and hazard ratios (HRs) were calculated to the factors associated with falls among participants. Results The median follow-up time for participants was 2.42 years. During the follow-up period, the incidence of falls among all participants was 21.96%. After adjusting for covariates in Cox regression models, T2DM remained a significant risk factor for falls, with HR of 1.781 (95% CI: 1.600-1.983) in the unadjusted covariates model and 1.757 (1.577–1.957) in the adjusted covariates model. Female (1.286, 1.136–1.457), older age (≥ 80: 1.448, 1.214–1.729), single marital status (1.239, 1.039–1.477), lower education level (primary school and below: 1.619, 1.004–1.361), hypertension (1.149, 1.026–1.286) and stroke (1.619, 1.176–2.228) were associated with a higher risk of falls, whereas everyday physical exercise (0.793, 0.686–0.918) was associated with a lower risk of falls. Conclusion Falls are common, with risks between T2DM and falls quantified and several factors investigated in the longitudinal cohort study among community-dwelling elderly people in Guangzhou, China. Targeted action on the risk factors may reduce the burden of falls in elderly people with T2DM in the future.

Abstract Background Casein kinase 1α (CK1α), expressed in both ovarian germ and somatic cells, is involved in the initial meiosis and primordial follicle formation of mouse oocytes. Using in vitro and in vivo experiments in this study, we explored the function and mechanism of CK1α in estrogen synthesis in mice ovarian granulosa cells. Methods A CK1α knockout (cKO) mouse model, targeted specifically to ovarian granulosa cells (GCs), was employed to establish the influence of CK1α on in vivo estrogen synthesis. The influence of CK1α deficiency on GCs was determined in vivo and in vitro by immunofluorescence analysis and Western blot assay. Transcriptome profiling, differentially expressed genes and gene functional enrichment analyses, and computation protein–protein docking, were further employed to assess the CK1α pathway. Furthermore, wild-type female mice were treated with the CK1α antagonist D4476 to elucidate the CK1α's role in estrogen regulation. Results Ovarian GCs CK1α deficiency impaired fertility and superovulation of female mice; also, the average litter size and the estradiol (E2) level in the serum of cKO female mice were decreased by 57.3% and 87.4% vs. control mice, respectively. This deficiency disrupted the estrous cycle and enhanced the apoptosis in the GCs. We observed that CK1α mediated the secretion of estradiol in mouse ovarian GCs via the cytochrome P450 subfamily 19 member 1 (CYP19A1). Conclusions These findings improve the existing understanding of the regulation mechanism of female reproduction and estrogen synthesis. Trial registration Not applicable.

Abstract Background Distal tibial fractures represent common lower limb injuries, frequently accompanied by significant soft tissue damage. The optimal surgical approach for managing these fractures remains a topic of considerable debate. The aim of this study was to perform a comparative analysis of the outcomes associated with retrograde intramedullary tibial nails (RTN) and minimally invasive plate osteosynthesis (MIPO) in the context of treating extra-articular distal tibial fractures. Methods A retrospective review was conducted on a cohort of 48 patients who sustained extra-articular distal tibial fractures between December 2019 and December 2021. Patients underwent either RTN or MIPO procedures. Various parameters, including operative duration, intraoperative fluoroscopy exposure, time to union, duration until full weight-bearing, American Orthopedic Foot and Ankle Society (AOFAS) scores, and complications, were recorded and compared between the two treatment groups. Results No statistically significant differences were observed in operative duration, time to union, angulation of the distal tibial coronal plane, or AOFAS scores between the RTN and MIPO groups. However, the RTN group had a higher average number of intraoperative fluoroscopy images (8.2 ± 2.3) compared to the MIPO group (4.1 ± 2.0). The RTN group demonstrated shorter average hospital stays (7.1 ± 1.4 days) and a quicker return to full weight-bearing (9.9 ± 1.3 weeks), which were significantly superior to the MIPO group (9.0 ± 2.0 days and 11.5 ± 1.5 weeks, respectively). In terms of complications, the RTN group had one case of superficial infection, whereas the MIPO group exhibited two cases of delayed union and nonunion, two occurrences of deep infection, and an additional three cases of superficial infection. Conclusions Both RTN and MIPO are effective treatment options for extra-articular distal tibial fractures. However, RTN may offer superior outcomes in terms of decreased inpatient needs, faster return to full weight-bearing capacity, and a lower rate of complications.

Abstract Background This study aimed to clarify medical-nonmedical difference on the relationship between social capital, mental health and digital health literacy of university students in China, and furtherly provide evidence-based suggestions on the improvement of the digital health literacy for the university students. Methods The snowball sampling method was used to collect data from the university students (including medical students and nonmedical students) through online questionnaires, and finally 1472 university students were included for the data analysis, of whom, 665 (45.18%) were medical students, 807 (54.82%) were nonmedical students; 462 (31.39%) were male, 1010 (68.61%) were female. Mean value of the age was 21.34 ± 2.33 for medical students vs. 20.96 ± 2.16 for nonmedical students. Descriptive analysis, chi-square test analysis, one-way Analysis of Variance (conducted by SPSS) and structural equation modeling (conducted by AMOS) were employed to explore the difference on the relationship between social capital, mental health and digital health literacy between the medical students and nonmedical students. Results The mean value of the digital health literacy was 36.27 (37.33 for medical students vs. 35.39 for nonmedical students). The SEM analysis showed that there was a statistically positive correlation between social capital and digital health literacy (stronger among the nonmedical students (0.317) than medical students (0.184)). Mental health had a statistically positive impact on the digital health literacy among medical students (0.242), but statistically significant correlation was not observed in nonmedical students (0.017). Social capital was negatively correlated with the mental health for both medical students and NMS (stronger among the nonmedical students (0.366) than medical students (0.255)). And the fitness indices of SEM were same between medical students and nonmedical students (GFI = 0.911, AGFI = 0.859, CFI = 0.922, RMSEA = 0.074). Conclusion The digital health literacy of the university student was relatively high. Both social capital and mental health could exert a positive effect on digital health literacy, while social capital was found to be positively associated with mental health. Statistical difference was found between medical students and nonmedical students on the above correlations. Implications were given on the improvement of the digital health literacy among university students in China.

Abstract Previous studies have shown that the heterogeneity of tumor-associated fibroblasts (CAFs) in the tumor microenvironment may play a critical role in tumorigenesis; however, the biological function of CAFs in pancreatic cancer is still controversial. In this study, we found that CD105-positive (CD105+) CAF-derived exosomes significantly promoted the proliferative and invasive metastatic abilities of pancreatic cancer cells. Furthermore, RNA-seq and qRT‒PCR experiments revealed circAMPK1 as a key molecule in exosomes from CD105+ CAFs that mediates the malignant progression of pancreatic cancer. Furthermore, we demonstrated that circAMPK1 encodes a novel protein (AMPK1-360aa) in pancreatic cancer cells. This protein competes with AMPK1 to bind to the ubiquitination ligase NEDD4, which inhibits AMPK1 protein degradation and ubiquitination and thereby increases AMPK1 levels. Finally, we demonstrated that AMPK1-360aa induces cellular autophagy via NEDD4/AMPK1 to promote the proliferation and invasion of pancreatic cancer cells. In summary, circAMPK1 in CD105+ CAF-derived exosomes may mediate pancreatic cancer cell proliferation and invasive metastasis by inducing autophagy in target cells. Moreover, circAMPK1 may competitively bind to ubiquitinating enzymes through the encoded protein AMPK1-360aa, which in turn inhibits the ubiquitination-mediated degradation of AMPK1 and contributes to the upregulation of AMPK1 expression, thus inducing cellular autophagy to mediate the malignant progression of pancreatic cancer.

Abstract Background A cross-sectional population-based survey in the Beichen district of Tianjin was conducted to estimate the prevalence of dry eye disease (DED) among the population over 50 years old with Dry Eye Workshop (DEWS) II and Chinese expert consensus (CEC) criteria. Methods A total of 5791 subjects over 50 years old were enrolled. Ocular surface disease index (OSDI) questionnaire, lipid layer thickness (LLT), partial blink ratio (PBR), fluorescein tear film breakup time (FBUT), Schirmer I test (SIT), fluorescein staining, meibomian gland dropout, meibomian gland expression scores (MES) and quantity scores (MQS) was assessed. Additionally, basic information, weight, disease history, living habits, anxiety, and depression condition were collected. Results According to the CEC, the prevalence of DED was 39.0%, whereas 44.0% based on DEWS II. The prevalence of DED increased with age and was substantially greater among women (41.1%, 95% CI, 39.5-42.6%) than males (35.1%, 95% CI, 33.1 -37.2%) (p

Abstract Objectives To apply cardiac magnetic resonance imaging (CMR) for detailed myocardial characterization in uremic cardiomyopathy (UC), hypertensive cardiomyopathy (HTN), and hypertrophic cardiomyopathy (HCM) aiming to enrich the understanding of UC’s etiology and further support the development of therapeutic strategies. Methods A total of 152 patients (age: 49.2 ± 9.9 years; 65.8% male) underwent routine CMR from June 2016 to March 2023. Retrospectively, 53 patients with UC, 39 patients with HTN, 30 patients with HCM, and 30 healthy controls were included. Functional analysis, feature tracking of the left ventricle and left atrium, and myocardial T1, T2, and T2* mapping were performed. Statistical analysis included Pearson correlation and ROC analysis to define correlations and discriminators between groups. Results UC patients demonstrated significantly higher native T1 (p

Abstract Background The fruit of Phyllanthus emblica L., a traditional medicine in China and India, is used to treat diabetes mellitus. Its water extract (WEPE) has demonstrated hypoglycemic effects in diabetic rats, but its mechanisms on glucose utilization and insulin resistance in skeletal muscle remain unclear. Therefore, this study aims to investigate the effects and underlying mechanisms of WEPE on glucose utilization and insulin resistance using C2C12 myotubes. Methods Effects of WEPE on glucose uptake, GLUT4 translocation, and AMPK and AKT phosphorylation were investigated in C2C12 myotubes and palmitate-treated myotubes. An AMPK inhibitor and siRNA were used to explore the mechanisms of WEPE. Glucose uptake was determined using a 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino)-2-deoxyglucose (2-NBDG) uptake assay, and protein expression and GLUT4 translocation were assessed via western blotting. Results In normal myotubes, WEPE significantly stimulated glucose uptake and GLUT4 translocation to the plasma membrane at concentrations of 125 and 250 µg/mL. This was accompanied by an increase in the phosphorylation of AMPK and its downstream targets. However, both compound C and AMPK siRNA blocked the WEPE-induced GLUT4 translocation and glucose uptake. Moreover, pretreatment with STO-609, a calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ) inhibitor, inhibited WEPE-induced AMPK phosphorylation and attenuated the WEPE-stimulated glucose uptake and GLUT4 translocation. In myotubes treated with palmitate, WEPE prevented palmitate-induced insulin resistance by enhancing insulin-mediated glucose uptake and AKT phosphorylation. It also restored the insulin-mediated translocation of GLUT4 from cytoplasm to membrane. However, these effects of WEPE on glucose uptake and GLUT4 translocation were blocked by pretreatment with compound C. Conclusions WEPE significantly stimulated basal glucose uptake though CaMKKβ/AMPK pathway and markedly ameliorated palmitate-induced insulin resistance by activating the AMPK pathway in C2C12 myotubes.

Considering the significance of lifelong learning in advancing active aging in aging societies, the ability to engage in self-directed learning plays a crucial role for adults. There are many self-directed learning (SDL) tools available that measure the SDL abilities of nursing students and healthcare professionals. However, fewer SDL tools specifically designed for middle-aged and older adults have been developed. The purpose of this research was to examine and confirm the factor structure and the internal consistency of the SRSSDL-adult scale, specifically for middle-aged and older adult learners enrolled in senior learning centers. A cross-sectional method was adopted. Both Exploratory Factor Analysis and Confirmatory Factor Analysis were conducted to assess the structural validity of the scale. The internal consistency was determined using the Cronbach's Alpha coefficient. The results indicated that the five factors -- learning needs assessment skills, learning planning skills, learning execution skills, self-assessment skills, and interpersonal skills -- showed acceptable levels of reliability. The revised 25-item SRSSDL-adult scale was found to be a valid measure of middle-aged and older adults' self-directed learning abilities in the context of senior education programs. The findings of this study have the potential to be utilized by educational institutions and educators involved in senior education programs.

Mycobacteria are causative agents of tuberculosis (TB), which is a global health concern. Drug-resistant TB strains are rapidly emerging, thereby necessitating the urgent development of new drugs. Two-component signal transduction systems (TCSs) are signaling pathways involved in the regulation of various bacterial behaviors and responses to environmental stimuli. Applying specific inhibitors of TCSs can disrupt bacterial signaling, growth, and virulence, and can help combat drug-resistant TB. We conducted a comprehensive pharmacophore-based inhibitor screening and biochemical and biophysical examinations to identify, characterize, and validate potential inhibitors targeting the response regulators PhoP and MtrA of mycobacteria. The constructed pharmacophore model Phar-PR-n4 identified effective inhibitors of formation of the PhoP–DNA complex: ST132 (IC50 = 29 ± 1.6 µM) and ST166 (IC50 = 18 ± 1.3 µM). ST166 (KD = 18.4 ± 4.3 μM) and ST132 (KD = 14.5 ± 0.1 μM) strongly targeted PhoP in a slow-on, slow-off manner. The inhibitory potency and binding affinity of ST166 and ST132 for MtrAC were comparable to those of PhoP. Structural analyses and molecular dynamics simulations revealed that ST166 and ST132 mainly interact with the α8-helix and C-terminal β-hairpin of PhoP, with functionally essential residue hotspots for structure-based inhibitor optimization. Moreover, ST166 has in vitro antibacterial activity against Macrobacterium marinum. Thus, ST166, with its characteristic 1,2,5,6-tetrathiocane and terminal sulphonic groups, has excellent potential as a candidate for the development of novel antimicrobial agents to combat pathogenic mycobacteria.

CRISPR-Cas9 systems constitute bacterial adaptive immune systems that protect against phage infections. Bacteriophages encode anti-CRISPR proteins (Acrs) that mitigate the bacterial immune response. However, the structural basis for their inhibitory actions from a molecular perspective remains elusive. In this study, through microsecond atomistic molecular dynamics simulations, we demonstrated the remarkable flexibility of Streptococcus pyogenes Cas9 (SpyCas9) and its conformational adaptability during interactions with AcrIIA4 and AcrIIA2. Specifically, we demonstrated that the binding of AcrIIA4 and AcrIIA2 to SpyCas9 induces a conformational rearrangement that causes spatial separation between the nuclease and cleavage sites, thus making the endonuclease inactive. This separation disrupts the transmission of signals between the protospacer adjacent motif recognition and nuclease domains, thereby impeding the efficient processing of double-stranded DNA. The simulation also reveals that AcrIIA4 and AcrIIA2 cause different structural variations of SpyCas9. Our research illuminates the precise mechanisms underlying the suppression of SpyCas9 by AcrIIA4 and AcrIIA2, thus presenting new possibilities for controlling genome editing with higher accuracy.

A detrimental feedback loop between hypoxia and oxidative stress consistently drives macrophage polarization toward a pro-inflammatory M1 phenotype, thus persistently aggravating rheumatoid arthritis (RA) progression. Herein, an enzyme-catalyzed nanoplatform with synergistic hypoxia-relieving and reactive oxygen species (ROS)-scavenging properties was developed using bovine serum albumin-bilirubin-platinum nanoparticles (BSA-BR-Pt NPs). Bilirubin was employed to eliminate ROS, while platinum exhibited a synergistic effect in scavenging ROS and simultaneously generated oxygen. In mice RA model, BSA-BR-Pt NPs treatment exhibited superior effects, resulting in significant improvements in joint inflammation, cartilage damage, and bone erosion, compared to methotrexate, the most widely used antirheumatic drug. Mechanistically, RNA-sequencing data and experimental results elucidated that BSA-BR-Pt NPs induced a re-polarization of hypoxic M1 macrophages to M2 macrophages via switching glycolysis to oxidative phosphorylation through the inhibition of HIF-1α pathway. Collectively, this research for the first time elaborated the underlying mechanism of enzyme-catalyzed nanoplatform in orchestrating macrophage polarization, and identified a novel therapeutic strategy for RA and other inflammatory disorders.

Abstract Li metal batteries have been widely expected to break the energy‐density limits of current Li‐ion batteries, showing impressive prospects for the next‐generation electrochemical energy storage system. Although much progress has been achieved in stabilizing the Li metal anode, the current Li electrode still lacks efficiency and safety. Moreover, a practical Li metal battery requires a thickness‐controllable Li electrode to maximally balance the energy density and stability. However, due to the stickiness and fragile nature of Li metal, manufacturing Li ingot into thin electrodes from conventional approaches has historically remained challenging, limiting the sufficient utilization of energy density in Li metal batteries. Aiming at the practical application of Li metal anode, the current issues and their initiation mechanism are comprehensively summarized from the stability and processability perspectives. Recent advances in robust and ultra‐thin Li metal anode are outlined from methodology innovation to provide an overall insight. Finally, challenges and prospective developments regarding this burgeoning field are critically discussed to afford future outlooks. With the development of advanced processing and modification technology, we are optimistic that a truly great leap will be achieved in the foreseeable future toward the industrial application of Li metal batteries.

Abstract Background The undergraduate tutorial system (UTS) is a crucial measure in China for adhering to the principle of prioritizing foundational education, innovating the undergraduate talent training mode, and building a powerful country of higher education. This study investigated undergraduate students’ satisfaction with UTS and the influencing factors, aiming to promote the healthy and sustainable development of UTS and provide practical implications and suggestions for universities. Methods Based on relevant theories, we conducted a survey study and leveraged structural equation modeling to assess students’ satisfaction with UTS and explore the influencing factors. Results Our Pearson correlation analysis showed that students’ satisfaction with mentors was positively correlated with dimensions such as humanistic care (r = 0.844, P

Abstract Background Compared with moderate-intensity continuous training (MICT), high-intensity interval training (HIIT) has at least a comparable effect on inhibiting an increase in fat. However, few studies have been conducted to examine the effects of detraining on body fat in rats fed a high-fat diet. The present study aimed to compare the effects of 10 weeks of HIIT or MICT as well as 6 weeks of detraining on body fat in rats fed a high-fat diet. Methods After being fed a high-fat diet for 8 weeks, 54 female rats were randomly assigned to six groups: (1) CON-10, sedentary control for 10 weeks; (2) MICT-10, 10 weeks of MICT; (3) HIIT-10, 10 weeks of HIIT; (4) CON-16, sedentary control for 16 weeks; (5) MICT-16, 10 weeks of MICT followed by 6 weeks of training cessation; and (6) HIIT-16, 10 weeks of HIIT followed by 6 weeks of training cessation. The training was performed 5 days/week. The subcutaneous adipose tissue (inguinal; SCAT), visceral adipose tissue (periuterine; VAT) and serum lipid profile were analysed after 10 or 16 weeks. Adipose tissue triglyceride lipase (ATGL) protein expression in VAT was assessed by western blotting. Results HIIT-10 and MICT-10 prevented the increase in SCAT, VAT and serum lipid levels seen in the CON group. During the 6-week detraining period, HIIT continued to prevent the increase in adipose tissue mass observed in the CON group, whereas MICT at least maintained this inhibition. The inhibition of fat mass increase was mainly the result of preventing adipocyte hypertrophy. The HIIT-10 and HIIT-16 groups showed the highest ATGL protein expression. Conclusions HIIT has a comparable effect to MICT on inhibiting fat accumulation in female rats; however, the inhibition of SCAT and VAT increase by HIIT is superior to MICT after short-term training cessation. Graphical Abstract

Abstract Background Given the significant role of immune-related genes in uterine corpus endometrial carcinoma (UCEC) and the long-term outcomes of patients, our objective was to develop a prognostic risk prediction model using immune-related genes to improve the accuracy of UCEC prognosis prediction. Methods The Limma, ESTIMATE, and CIBERSORT methods were used for cluster analysis, immune score calculation, and estimation of immune cell proportions. Univariate and multivariate analyses were utilized to develop a prognostic risk model for UCEC. Risk model scores and nomograms were used to evaluate the models. String constructs a protein-protein interaction (PPI) network of genes. The qRT-PCR, immunofluorescence, and immunohistochemistry (IHC) all confirmed the genes. Results Cluster analysis divided the immune-related genes into four subtypes. 33 immune-related genes were used to independently predict the prognosis of UCEC and construct the prognosis model and risk score. The analysis of the survival nomogram indicated that the model has excellent predictive ability and strong reliability for predicting the survival of patients with UCEC. The protein-protein interaction network analysis of key genes indicates that four genes play a pivotal role in interactions: GZMK, IL7, GIMAP, and UBD. The quantitative real-time polymerase chain reaction (qRT-PCR), immunofluorescence, and immunohistochemistry (IHC) all confirmed the expression of the aforementioned genes and their correlation with immune cell levels. This further revealed that GZMK, IL7, GIMAP, and UBD could potentially serve as biomarkers associated with immune levels in endometrial cancer. Conclusion The study identified genes related to immune response in UCEC, including GZMK, IL7, GIMAP, and UBD, which may serve as new biomarkers and therapeutic targets for evaluating immune levels in the future.

Didymocarpus pingyuanensis, endemic to the Danxia landscape in Pingyuan County, Guangdong, China, is described and illustrated here. This species can be distinguished from other members of Didymocarpus sect. Heteroboea by its calyx deeply 5-lobed to about three quarters of its length. The phylogenetic position of the new species within Didymocarpus was examined using nuclear ribosomal internal transcribed spacer (ITS) sequences. Based on phylogenetics analysis and morphological evidence, we propose two new combinations, elevating the two varieties to species level, namely D. yinzhengii and D. gamosepalus.

High-precision positioning and navigation are necessary for autonomous driving. GNSS RTK and INS integrated system is commonly used in vehicular navigation. But it suffers from severe signal reflections and blockages of GNSS signals and error accumulation of INS with MEMS-IMU in GNSS-challenging environment. In addition, high-definition (HD) maps in vector format and light detection and ranging (LiDAR) are two common options for intelligent vehicles. A tightly coupled localization method with vector HD map, LiDAR, GNSS RTK, and INS is proposed to take advantage of their complementary characteristics to accurately navigate a vehicle in a GNSS-challenging environment. The method is based on a particle filter (PF) framework. Lateral positions of particles are constrained by LiDAR measurements and lane information in the vector HD map. A constrained and damped LAMBDA searching method is proposed to update particle weights, aiming to find accurate longitudinal localization. Experimental results prove that our method can maintain sub-meter level horizontal positioning accuracy in GNSS-challenging environment, with improvements of (77%, 75%, 64% and 65%), regarding to three-dimensional position and yaw, compared to traditional GNSS-RTK/INS integration, while the improvement of the popular GNSS-RTK/INS/LiDAR integrated framework LIO-SAM is (16%, 53%, 48% and 51%).

Subclinical hypothyroidism (SCH) is closely related to insulin resistance, and thyroid-stimulating hormone (TSH) level is an independent factor for insulin resistance associated with subclinical hypothyroidism. This study aims to explore the effects of TSH levels on insulin signal transduction in adipocytes and to establish the role of endoplasmic reticulum (ER) stress in this process. In this study, the SCH mouse model was established, and 3T3-L1 adipocytes were treated with TSH or tunicamycin (TM), with or without 4-phenylbutyric acid (4-PBA), an inhibitor of ER stress. Subclinical hypothyroidism mice exhibited impaired glucose tolerance, inactivation of the IRS-1/AKT pathway, and activation of the IRE1/JNK pathway in adipose tissue, which can all be alleviated by 4-PBA. Supplementation with levothyroxine restored the TSH to normal, alongside alleviated ER stress and insulin resistance in SCH mice, which is characterized by improved glucose tolerance, decreased mRNA expression of IRE1, and decreased phosphorylation of JNK in adipose tissue. In 3T3-L1 adipocytes, TSH induces insulin resistance, leading to a decrease in glucose uptake. This effect is mediated by the downregulation of IRS-1 tyrosine phosphorylation, reduced AKT phosphorylation, and inhibited GLUT4 protein expression. Notably, all these effects can be effectively reversed by 4-PBA. Moreover, TSH induced TNF-α and IL-6 production and upregulated the expression of ER stress markers. Similarly, these changes can be recovered by 4-PBA. These findings indicate that TSH has the capability to induce insulin resistance in adipocytes. The mechanism through which TSH disrupts insulin signal transduction appears to involve the ER stress–JNK pathway.

Abstract Alzheimer's disease (AD) is a neurodegenerative disorder characterized primarily by cognitive impairment. The motivation of this paper is to explore the impact of the visual information transmission pathway (V–H pathway) on AD, and the following feature were observed: Hemoglobin expression on the V–H pathway becomes dysregulated as AD occurs so as to the pathway becomes dysfunctional. According to the feature, the following conclusion was proposed: As AD occurs, abnormal tau proteins penetrate bloodstream and arrive at the brain regions of the pathway. Then the tau proteins or other toxic substances attack hemoglobin molecules. Under the attack, hemoglobin expression becomes more dysregulated. The dysfunction of V–H pathway has an impact on early symptoms of AD, such as spatial recognition disorder and face recognition disorder.

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

Background : Triglyceride glucose (TyG) and TyG-body mass index (TyG-BMI) are reliable surrogate indices of insulin resistance and used for risk stratification and outcome prediction in patients with atherosclerotic cardiovascular disease (ASCVD). Here, we inserted estimated average glucose (eAG) into the TyG (TyAG) and TyG-BMI (TyAG-BMI) as derived parameters and explored their clinical significance in cardiovascular risk prediction. Methods : This was a population-based cohort study of 9,944 Chinese patients with ASCVD. The baseline admission fasting glucose and A1C-derived eAG values were recorded. Cardiovascular events (CVEs) that occurred during an average of 38.5 months of follow-up were recorded. We stratified the patients into four groups by quartiles of the parameters. Baseline data and outcomes were analyzed. Results : Distribution of the TyAG and TyAG-BMI indices shifted slightly toward higher values (the right side) compared with TyG and TyG-BMI, respectively. The baseline levels of cardiovascular risk factors and coronary severity increased with quartile of TyG, TyAG, TyG-BMI, and TyAG-BMI (all P

Abstract Background Ankylosing spondylitis (AS) with radiographic damage is more prevalent in men than in women. IL-17, which is mainly secreted from peripheral blood mononuclear cells (PBMCs), plays an important role in the development of AS. Its expression is different between male and female. However, it is still unclear whether sex dimorphism of IL-17 contribute to sex differences in AS. Methods GSE221786, GSE73754, GSE25101, GSE181364 and GSE205812 datasets were collected from the Gene Expression Omnibus (GEO) database. Differential expressed genes (DEGs) were analyzed with the Gene Set Enrichment Analysis (GSEA), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) methods. CIBERSORTx and EcoTyper algorithms were used for immune infiltration analyses. Machine learning based on the XGBoost algorithm model was used to identify the impact of DEGs. The Connectivity Map (CMAP) database was used as a drug discovery tool for exploring potential drugs based on the DEGs. Results According to immune infiltration analyses, T cells accounted for the largest proportion of IL-17-secreting PBMCs, and KEGG analyses suggested an enhanced activation of mast cells among male AS patients, whereas the expression of TNF was higher in female AS patients. Other signaling pathways, including those involving metastasis-associated 1 family member 3 (MAT3) or proteasome, were found to be more activated in male AS patients. Regarding metabolic patterns, oxidative phosphorylation pathways and lipid oxidation were significantly upregulated in male AS patients. In XGBoost algorithm model, DEGs including METRN and TMC4 played important roles in the disease process. we integrated the CMAP database for systematic analyses of polypharmacology and drug repurposing, which indicated that atorvastatin, famciclocir, ATN-161 and taselisib may be applicable to the treatment of AS. Conclusions We analyzed the sex dimorphism of IL-17-secreting PBMCs in AS. The results showed that mast cell activation was stronger in males, while the expression of TNF was higher in females. In addition, through machine learning and the CMAP database, we found that genes such as METRN and TMC4 may promote the development of AS, and drugs such as atorvastatin potentially could be used for AS treatment.

It is known that sialyllactose (SL) in mammalians is a major source of sialic acid (Sia), which can further form cytidine monophosphate sialic acid (CMP-Sia), and the final product is polysialic acid (polySia) using polysialyltransferases (polySTs) on the neural cell adhesion molecule (NCAM). This process is called NCAM polysialylation. The overexpression of polysialylation is strongly related to cancer cell migration, invasion, and metastasis. In order to inhibit the overexpression of polysialylation, in this study, SL was selected as an inhibitor to test whether polysialylation could be inhibited. Our results suggest that the interactions between the polysialyltransferase domain (PSTD) in polyST and CMP-Siaand the PSTD and polySia could be inhibited when the 3′-sialyllactose (3′-SL) or 6′-sialyllactose (6′-SL) concentration is about 0.5 mM or 6′-SL and 3 mM, respectively. The results also show that SLs (particularly for 3′-SL) are the ideal inhibitors compared with another two inhibitors, low-molecular-weight heparin (LMWH) and cytidine monophosphate (CMP), because 3’-SL can not only be used to inhibit NCAM polysialylation, but is also one of the best supplements for infant formula and the gut health system.

Lappula effusa D.H.Liu & W.J.Li, a new species of Boraginaceae from Xinjiang, China, is described and illustrated in this study. The new species is morphologically similar to Lappula himalayensis and L. tadshikorum. However, it can be distinguished from the compared species by several characteristics, such as: stem single, erect, frequently branched at middle and above, densely spreading hispid, hairs discoid at base; corolla white or blue; fruit compressed, heteromorphic nutlets with two rows of marginal glochids, nutlets acute ovoid, disc narrowly ovate-triangular. The diagnosis of the new species is supported with comprehensive investigation including photographs, detailed description, notes on etymology, distribution and habitat, conservation status, as well as comparisons with morphologically similar species.

Abstract Introduction To explore the diagnostic value of high-resolution ultrasound combined with multi-slice computer tomography (MSCT) for pediatric intra-abdominal hernias (IAHs), and to analyze the potential causes for missed diagnosis and misdiagnosis of IAHs in children. Methods A retrospective analysis was conducted on 45 children with surgically confirmed IAHs. The diagnostic rate of IAHs by preoperative high-resolution ultrasound combined with MSCT was compared with that of intraoperative examination, and the potential causes for missed diagnosis and misdiagnosis by the combination method were analyzed. Results Forty-five cases of pediatric IAHs were categorized into primary (25/45, 55.5%) and acquired secondary hernias (20/45, 44.5%). Among children with primary hernias, mesenteric defects were identified as the predominant subtype (40%). Acquired secondary hernias typically resulted from abnormal openings in the abdominal wall or band adhesions due to trauma, surgery, or inflammation. In particular, adhesive band hernias were the major type in children with acquired secondary hernias (40%). The diagnostic rate of high-resolution ultrasound was 77.8%, with “cross sign” as a characteristic ultrasonic feature. Among 10 cases of missed diagnosis or misdiagnosis, 5 were finally diagnosed as IAHs by multi-slice computer tomography (MSCT). Overall, the diagnostic rate of pediatric IAHs by preoperative ultrasound combined with radiological imaging reached 88.9%. Discussion IAHs in children, particularly mesenteric defects, are prone to strangulated intestinal obstruction and necrosis. High-resolution ultrasound combined with MSCT greatly enhances the diagnostic accuracy of pediatric IAHs.

Abstract Background Pretransplant type 2 diabetes mellitus (T2DM) is associated with increased cardiovascular and all-cause mortality after heart transplant (HT), but the underlying causes of this association remain unclear. The purpose of this research was to examine the impact of T2DM on left ventricular (LV) myocardial deformation and myocardial perfusion following heart transplantation using cardiovascular magnetic resonance imaging. Methods We investigated thirty-one HT recipients with pretransplant T2DM [HT(DM+)], thirty-four HT recipients without pretransplant T2DM [HT(DM−)] and thirty-six controls. LV myocardial strains, including the global longitudinal, radial, and circumferential strain (GLS, GRS and GCS, respectively), were calculated and compared among groups, as were resting myocardial perfusion indices, which included time to peak myocardial signal intensity (TTM), maximum signal intensity (MaxSI), and Upslope. The relationships between LV strain parameters or perfusion indices and biochemical indicators were determined through Spearman’s analysis. The impact of T2DM on LV strains in HT recipients was assessed using multivariable linear regression analyses with backward stepwise selection. Results In the HT(DM+) group, the LV GLS, GRS, and GCS exhibited significantly lower magnitudes than those in both the HT(DM−) and control groups. TTM was higher in the HT(DM+) group than in both the HT(DM−) and control groups, while no significant differences were observed among the groups regarding Upslope and MaxSI. There was a negative correlation between glycated hemoglobin and the magnitude of strains (longitudinal, r = − 0.399; radial, r = − 0.362; circumferential, r = − 0.389) (all P

Abstract This study probes the utility of biomarkers for microsatellite instability (MSI) detection and elucidates the molecular dynamics propelling colorectal cancer (CRC) progression. We synthesized a primer panel targeting 725 MSI loci, informed by The Cancer Genome Atlas (TCGA) and ancillary databases, to construct an amplicon library for next-generation sequencing (NGS). K-means clustering facilitated the distillation of 8 prime MSI loci, including activin A receptor type 2A (ACVR2A). Subsequently, we explored ACVR2A’s influence on CRC advancement through in vivo tumor experiments and hematoxylin–eosin (HE) staining. Transwell assays gauged ACVR2A’s role in CRC cell migration and invasion, while colony formation assays appraised cell proliferation. Western blotting illuminated the impact of ACVR2A suppression on CRC’s PI3K/AKT/mTOR pathway protein expressions under hypoxia. Additionally, ACVR2A’s influence on CRC-induced angiogenesis was quantified via angiogenesis assays. K-means clustering of NGS data pinpointed 32 MSI loci specific to tumor and DNA mismatch repair deficiency (dMMR) tissues. ACVR2A emerged as a pivotal biomarker, discerning MSI-H tissues with 90.97% sensitivity. A curated 8-loci set demonstrated 100% sensitivity and specificity for MSI-H detection in CRC. In vitro analyses corroborated ACVR2A’s critical role, revealing its suppression of CRC proliferation, migration, and invasion. Moreover, ACVR2A inhibition under CRC-induced hypoxia markedly escalated MMP3, CyclinA, CyclinD1, and HIF1α protein expressions, alongside angiogenesis, by triggering the PI3K/AKT/mTOR cascade. The 8-loci ensemble stands as the optimal marker for MSI-H identification in CRC. ACVR2A, a central element within this group, deters CRC progression, while its suppression amplifies PI3K/AKT/mTOR signaling and angiogenesis under hypoxic stress.

Abstract Background Endocrine resistance driven by sustained activation of androgen receptor (AR) signaling pathway in advanced prostate cancer (PCa) is fatal. Characterization of mechanisms underlying aberrant AR pathway activation to search for potential therapeutic strategy is particularly important. Rac GTPase-activating protein 1 (RACGAP1) is one of the specific GTPase-activating proteins. As a novel tumor proto-oncogene, overexpression of RACGAP1 was related to the occurrence of various tumors. Methods Bioinformatics methods were used to analyze the relationship of expression level between RACGAP1 and AR as well as AR pathway activation. qRT-PCR and western blotting assays were performed to assess the expression of AR/AR-V7 and RACGAP1 in PCa cells. Immunoprecipitation and immunofluorescence experiments were conducted to detect the interaction and co-localization between RACGAP1 and AR/AR-V7. Gain- and loss-of-function analyses were conducted to investigate the biological roles of RACGAP1 in PCa cells, using MTS and colony formation assays. In vivo experiments were conducted to evaluate the effect of RACGAP1 inhibition on the tumor growth. Results RACGAP1 was a gene activated by AR, which was markedly upregulated in PCa patients with CRPC and enzalutamide resistance. AR transcriptionally activated RACGAP1 expression by binding to its promoter region. Reciprocally, nuclear RACGAP1 bound to the N-terminal domain (NTD) of both AR and AR-V7, blocking their interaction with the E3 ubiquitin ligase MDM2. Consequently, this prevented the degradation of AR/AR-V7 in a ubiquitin-proteasome-dependent pathway. Notably, the positive feedback loop between RACGAP1 and AR/AR-V7 contributed to endocrine therapy resistance of CRPC. Combination of enzalutamide and in vivo cholesterol-conjugated RIG-I siRNA drugs targeting RACGAP1 induced potent inhibition of xenograft tumor growth of PCa. Conclusion In summary, our results reveal that reciprocal regulation between RACGAP1 and AR/AR-V7 contributes to the endocrine resistance in PCa. These findings highlight the therapeutic potential of combined RACGAP1 inhibition and enzalutamide in treatment of advanced PCa.