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Abstract NAD-dependent deacetylase Sirt2 is involved in mammalian metabolic activities, matching energy demand with energy production and expenditure, and is relevant to a variety of metabolic diseases. Here, we constructed Sirt2 knockout and adeno-associated virus overexpression mice and found that deletion of hepatic Sirt2 accelerated primary obesity and insulin resistance in mice with concomitant hepatic metabolic dysfunction. However, the key targets of Sirt2 are unknown. We identified the M2 isoform of pyruvate kinase (PKM2) as a key Sirt2 target involved in glycolysis in metabolic stress. Through yeast two-hybrid and mass spectrometry combined with multi-omics analysis, we identified candidate acetylation modification targets of Sirt2 on PKM2 lysine 135 (K135). The Sirt2-mediated deacetylation-ubiquitination switch of PKM2 regulated the development of glycolysis. Here, we found that Sirt2 deficiency led to impaired glucose tolerance and insulin resistance and induced primary obesity. Sirt2 severely disrupted liver function in mice under metabolic stress, exacerbated the metabolic burden on the liver, and affected glucose metabolism. Sirt2 underwent acetylation modification of lysine 135 of PKM2 through a histidine 187 enzyme active site-dependent effect and reduced ubiquitination of the K48 ubiquitin chain of PKM2. Our findings reveal that the hepatic glucose metabolism links nutrient state to whole-body energetics through the rhythmic regulation of Sirt2.

The effects of different dietary lipid levels on lipid accumulation, inflammatory response, serum bio-chemical index and histological features of intestine and hepatopancreas of O. macrolepis was experimentally evaluated in an eight-weeks study. Fish (initial weight 50.11 ± 2.86 g) were fed with five iso-nitrogenous diets (around 390 g/kg protein) varying with lipid level (5%, 7%, 9%, 11%, 13%, being LL5, LL7, LL9, LL11, and LL13 respectively) in triplicates. Results showed that the content of crude lipid in carcass and hepatopancreas were not affected by dietary lipid levels (P > 0.05). Serum ALT, TP, HDL-c and MDA, etc., were not significantly affected by diets (P > 0.05), while serum total antioxidant capacity in LL9 and LL11 groups were significantly higher than the other groups (P 0.05), while the height of intestine villus showed the higher trend in LL9 compared with other groups. The relative expression of lipid metabolism related genes (ppar α, cpt-1α, fas, and hsl) and immune response related genes (tlr 22, nrf 2, tnfα, and il-γ) in the hepatopancreas of fish fed diets differing in their crude lipid levels were not significantly different (P > 0.05). The results suggested that a proper dietary lipid level of 9%–11% could maintain higher antioxidant and health status of adult O.macrolepis.

Abstract Background The aim of the study was to evaluate the prognostic value of postoperative folate receptor‐positive circulating tumor cell (FR + CTC) detection in patients with stage I–III invasive adenocarcinoma (IAC) treated with surgery. Methods Patients with lung adenocarcinoma (LUAD) who underwent surgical resection in Peking University Cancer Hospital and received postoperative FR + CTC analysis from July 2016 to January 2021 were retrospectively collected. Comparisons between or among groups were made using the Kruskal‐Wallis or Mann–Whitney U tests. Survival curves were estimated using the Kaplan–Meier method and compared using the log‐rank test. Cox proportional hazard regression analyses were performed to explore the factors predicting recurrence and survival. Results There were significant differences between the high and low groups in terms of age (p = 0.002), postoperative CA199 (p = 0.038), and postoperative SCC (p = 0.024). There were no significant differences in the other indicators (all p>0.05). N stage 1, N stage 2, and neoadjuvant therapy (NAT) were independent risk factors for disease recurrence and death; pleural invasion (PI), and nerve invasion were independent risk factors for death. The Kaplan–Meier curve showed a notable trend for a worse disease‐free survival (DFS) or overall survival (OS) for patients with high levels of FR + CTCs in our study, but none of these were statistically significant. Conclusion The detection of FR + CTCs postoperatively was an independent predictor of recurrence in patients treated for stage I–III IAC. Standardized detection methods and optimal time points for assessment should be established in future studies.

Abstract Urban green space is a direct way to improve the carbon sink capacity of urban ecosystems. The carbon storage assessment of megacity green spaces is of great significance to the service function of urban ecosystems and the management of urban carbon zoning in the future. Based on multi-period remote sensing image data, this paper used the CASA model and the InVEST model to analyze the spatio-temporal variation and driving mechanism of carbon storage in Shenzhen green space and discussed the applicability of the two models to the estimation of carbon storage in urban green space. The research results showed that, from 2008 to 2022, in addition to the rapid expansion of construction land, the area of green space and other land types in Shenzhen showed a significant decrease trend. The estimation results of the carbon storage model showed that the carbon storage of green space shows a significant trend of reduction from 2008 to 2022, and the reduction amounts are 0.8 × 106 t (CASA model) and 0.64 × 106 t (InVEST model), respectively. The evaluation results of the model show that, in megacities, the spatial applicability of InVEST model is lower than that of CASA model, and the CASA model is more accurate in estimating the carbon storage of urban green space. The research results can provide a scientific basis for the assessment of the carbon sink capacity of megacity ecosystems with the goal of "dual carbon".

The production of selenium-enriched fish can contribute to alleviating selenium deficiency in human diets. However, it is still unclear which selenium source, as an additive, can efficiently and cost-effectively produce high-quality selenium-enriched fish. This study evaluated the effects of selenium nanoparticles (SeNP), selenite, and selenomethionine (SeMet) on the growth, antioxidant capacity, selenium content, selenium speciation, and meat quality of grass carp. Ten diets were prepared, including a basal diet (BD) and three concentrations (0.1, 0.3, and 0.9 mg/kg) of SeNP, selenite, and SeMet. A total of 600 fish (250.79 ± 1.57 g) were randomly assigned to 30 tanks (3 tanks/group). Fish were fed the experimental diet three times daily for 60 d. In this study, SeNP most significantly promoted the growth and antioxidant capacity of grass carp, with 0.3 mg/kg SeNP identified as the optimal additive concentration. Additionally, SeNP demonstrated equally excellent bioavailability as SeMet and significantly increased the content of SeMet in grass carp (Ctenopharyngodon idella) muscle. Furthermore, compared to SeMet and selenite, dietary SeNP could more significantly enhance the content of selenocysteine (SeCys2) and methylselenocysteine (MeSeCys) in grass carp muscle tissue. In addition, we have demonstrated that SeCys2 and MeSeCys promote apoptosis of cancer cells (HeLa) through the mitochondrial apoptotic pathway (involving Bax and Bcl-2). Furthermore, as an additive, 0.3 mg/kg SeNP significantly improved the flesh quality of grass carp by reducing crude fat and heavy metal content, as well as increasing the levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and the ratio of n-3/n-6 polyunsaturated fatty acid (PUFA). In summary, SeNP is the most suitable additive for producing selenium-enriched fish.

Background The number of patients undergoing joint replacement procedures is continuously increasing. Tele-equipment is progressively being employed for postrehabilitation of total hip and knee replacements. Gaining a comprehensive understanding of the experiences and requirements of patients undergoing total hip and knee arthroplasty who participate in telerehabilitation can contribute to the enhancement of telerehabilitation programs and the overall rehabilitation and care provided to this specific population. Objective To explore the needs and experiences of total hip and knee arthroplasty patients with telerehabilitation. Design Systematic review and qualitative synthesis. Methods Electronic databases PubMed, Web of Science, The Cochrane Library, Embase, CINAHL, Scopus, ProQuest, CNKI, Wanfang Data, VIP, and SinoMed were systematically searched for information on the needs and experiences of telerehabilitation for patients with total hip arthroplasty and total knee arthroplasty in qualitative studies. The search period was from the creation of the database to March 2024. Literature quality was assessed using the 2016 edition of the Australian Joanna Briggs Institute Centre for Evidence-Based Health Care Quality Assessment Criteria for Qualitative Research. A pooled integration approach was used to integrate the findings inductively. Results A total of 11 studies were included and 4 themes were identified: the desire to communicate and the need to acquire knowledge; accessible, high-quality rehabilitation services; positive psychological experiences; the dilemmas of participating in telerehabilitation. Conclusions This study's findings emphasize that the practical needs and challenges of total hip and knee arthroplasty patients’ participation in telerehabilitation should be continuously focused on, and the advantages of telerehabilitation should be continuously strengthened to guarantee the continuity of patients’ postoperative rehabilitation and to promote their postoperative recovery.

Abstract Galectin-3 levels have been studied as a potential biomarker for predicting cardiovascular (CV) risk and mortality in hemodialysis (HD) patients. Recently, a close relationship between galectin-3 and vascular calcification (VC) has been reported. Here, we investigated the role of VC as a mediating factor in the association between galectin-3 and mortality. Serum galectin-3 and baseline aortic arch calcification (AoAC) score were measured in 477 incident HD patients. Mortality data were obtained at a median follow-up of 40 months. Causal mediation analysis was performed to examine the effect of vascular risk factors on galectin-3-related mortality. The prevalence of AoAC in HD patients was 57% (n = 272), and elevated galectin-3 levels were associated with a significantly increased risk of AoAC. When the galectin-3 level was divided by the median level of 37 ng/mL, a higher galectin group increased the risk of all-cause mortality by 1.71-fold (95% CI 1.02–2.92, p = 0.048), even after adjustment for multiple CV risk factors. Mediation analysis showed that both the direct effect of the galectin-3 on mortality (β = 0.0368, bootstrapped 95% CI [0.0113–0.0622]) and the indirect effects were significant. AoAC score and high-sensitivity CRP levels significantly mediated the association between galectin-3 and mortality (total indirect effects: β = 0.0188, bootstrapped 95% CI [0.0066–0.0352]). This study suggests that the association between high galectin-3 and mortality may be partially mediated by higher VC and inflammatory state in HD patients.

It has been reported that selenium (Se) can reduce hepatopancreas lipid accumulation induced by high-fat diet. However, its mechanism is still unknown. This study aims to investigate the specific mechanisms by which Se alleviates high-fat diet-induced lipid accumulation. Grass carp were fed control diet (4.8% lipid, Con), high-fat diet (8.8% lipid, HFD) or HFD supplemented with 0.3 mg/kg nano-Se (HSe0.3) for 10 weeks. Growth performance, Se deposition, lipid accumulation, hepatic ultrastructure, and gene and protein expression levels associated with autophagy were examined. Furthermore, oleic acid (OA) was used to incubate the grass carp hepatocytes (L8824) for 24 h, and then the L8824 were incubated with sodium selenite in presence or absence of an autophagy inhibitor for 24 h. L8824 was analyzed for triglyceride concentration, immunofluorescence, and gene and protein expression levels associated with autophagy. We found that dietary nano-Se improved the growth of fish fed HFD and also decreased hepatosomatic index and intraperitoneal fat ratio of fish fed HFD (P

ABSTRACTZiziphus jujuba cv. Yulingdang (YLD) is a jujube cultivar that has been approved as a new plant cultivar by the State Forestry Administration of China. The physicochemical properties and antioxidant activity of YLD fruit were evaluated at seven stages of maturation, ranging from fruit setting to red ripe. The antioxidant activity of YLD fruit was assessed through total phenolics, total flavonoids, and methods including the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging rate, β-carotene-linoleic acid emulsification method, and reducing power. These measures were observed to decrease gradually as maturation progressed. The study also indicated an increase in total sugar and total acid levels, along with a decrease in moisture, soluble protein, and the sugar-acid ratio during maturation. Understanding this information is essential to fully exploit the commercial potential of YLD fruit.

The production of selenium-enriched fish contributes to alleviating selenium deficiency for humans. In this study, selenium nanoparticles (SeNPs) comparable in bioavailability to selenomethionine (SeMet), increased SeMet content in O. macrolepis (Onychostoma macrolepis) muscle. Additionally, dietary SeNPs significantly enhanced selenocysteine (SeCys2) and methylselenocysteine (MeSeCys) levels in O. macrolepis muscle. The effect of SeNPs on selenium speciation in grass carp muscle was consistent with O. macrolepis results. SeCys2 and MeSeCys showed antioxidant capacity in HEK293T cells, indicating enhanced health benefits of Se-enriched fish produced using SeNPs. Furthermore, the addition of 0.3 mg/kg SeNPs significantly improved the flesh quality of O. macrolepis by reducing the content of crude fat and heavy metals, as well as increasing the levels of crude protein, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and the ratio of n-3/n-6 polyunsaturated fatty acids (PUFAs). Therefore, selenium-enriched fish produced from SeNPs is a good source for improving human dietary selenium intake.

Abstract Emerging infectious diseases are a critical public health challenge in the twenty-first century. The recent proliferation of such diseases has raised major social and economic concerns. Therefore, early detection of emerging infectious diseases is essential. Subjects from five medical institutions in Beijing, China, which met the spatial-specific requirements, were analyzed. A quality control process was used to select 37,422 medical records of infectious diseases and 56,133 cases of non-infectious diseases. An emerging infectious disease detection model (EIDDM), a two-layer model that divides the problem into two sub-problems, i.e., whether a case is an infectious disease, and if so, whether it is a known infectious disease, was proposed. The first layer model adopts the binary classification model TextCNN-Attention. The second layer is a multi-classification model of LightGBM based on the one-vs-rest strategy. Based on the experimental results, a threshold of 0.5 is selected. The model results were compared with those of other models such as XGBoost and Random Forest using the following evaluation indicators: accuracy, sensitivity, specificity, positive predictive value, and negative predictive value. The prediction performance of the first-layer TextCNN is better than that of other comparison models. Its average specificity for non-infectious diseases is 97.57%, with an average negative predictive value of 82.63%, indicating a low risk of misdiagnosing non-infectious diseases as infectious (i.e., a low false positive rate). Its average positive predictive value for eight selected infectious diseases is 95.07%, demonstrating the model's ability to avoid misdiagnoses. The overall average accuracy of the model is 86.11%. The average prediction accuracy of the second-layer LightGBM model for emerging infectious diseases reaches 90.44%. Furthermore, the response time of a single online reasoning using the LightGBM model is approximately 27 ms, which makes it suitable for analyzing clinical records in real time. Using the Knox method, we found that all the infectious diseases were within 2000 m in our case, and a clustering feature of spatiotemporal interactions (P

In this paper, a double association-based evolutionary algorithm (denoted as DAEA) is proposed to solve many-objective optimization problems. In the proposed DAEA, a double association strategy is designed to associate solutions with each subspace. Different from the existing association methods, the double association strategy takes the empty subspace into account and associates it with a promising solution, which can facilitate the exploration of unknown areas. Besides, a new quality evaluation scheme is developed to evaluate the quality of each solution in subspace, where the convergence and diversity of each solution is first measured, and in order to evaluate the diversity of solutions more finely, the global diversity and local diversity is designed to measure the diversity of each solution. Then, a dynamic penalty coefficient is designed to balance the convergence and diversity by penalizing the global diversity distribution of solutions. The performance of DAEA is validated by comparing with five state-of-the-art many-objective evolutionary algorithms on a number of well-known benchmark problems with up to 20 objectives. Experimental results show that our DAEA has high competitiveness in solving many-objective optimizatiopn problems compared with the other compared algorithms.

A 90-day feeding trial was conducted to assess the effects of black soldier fly larvae meal (BSFLM) as a replacement for soybean meal (SM) on growth performance and flesh quality of grass carp. A total of 420 grass carp (299.93 ± 0.85 g) were randomly divided into 7 groups (triplicate) and fed 7 diets with SM substitution of 0% (SM, control), 15% (BSFLM15), 30% (BSFLM30), 45% (BSFLM45), 60% (BSFLM60), 75% (BSFLM75) and 100% (BSFLM100) by BSFLM. The growth performance of grass carp in the BSFLM75 and BSFLM100 groups were significantly lower compared to other groups (P

Focused on the unsteady property of a cavitating water jet issuing from an orifice nozzle in a submerged condition, this paper presents a fundamental investigation of the periodicity of cloud shedding and the mechanism of cavitation cloud formation and release by combining the use of high-speed camera observation and flow simulation methods. The pattern of cavitation cloud shedding is evaluated by analyzing sequence images from a high-speed camera, and the mechanism of cloud formation and release is further examined by comparing the results of flow visualization and numerical simulation. It is revealed that one pair of ring-like clouds consisting of a leading cloud and a subsequent cloud is successively shed downstream, and this process is periodically repeated. The leading cloud is principally split by a shear vortex flow along the nozzle exit wall, and the subsequent cloud is detached by a re-entrant jet generated while a fully extended cavity breaks off. The subsequent cavitation cloud catches the leading one, and they coalesce over the range of x/d≈1.8~2.5. Cavitation clouds shed downstream from the nozzle at two dominant frequencies. The Strouhal number of the leading cavitation cloud shedding varies from 0.21 to 0.29, corresponding to the injection pressure. The mass flow rate coefficient fluctuates within the range of 0.59~0.66 at the same frequency as the leading cloud shedding under the effect of cavitation.

Background: In recent years, global concern over increasing multidrug resistance (MDR) among various Salmonella serotypes has grown significantly. However, reports on MDR Salmonella Paratyphi B remain scarce, let alone the extensively drug-resistant (XDR) strains. Methods: In this retrospective study, we investigated the isolates of Salmonella Paratyphi B in Jiangsu Province over the past decade and carried out antimicrobial susceptibility tests, then the strains were sequenced and bioinformatics analyses were performed. Results: 27 Salmonella Paratyphi B strains were identified, of which the predominant STs were ST42 (11), ST86 (10), and ST2814 (5). Among these strains, we uncovered four concerning XDR Salmonella Paratyphi B ST2814 strains (4/5) which were previously unreported. These alarmingly resistant isolates showed resistance to all three major antibiotic classes for Salmonella treatment and even the last resort treatment tigecycline. Bioinformatics analysis revealed high similarity between the plasmids harbored by these XDR strains and diverse Salmonella serotypes and Escherichia coli from China and neighboring regions. Notably, these four plasmids carried the ramAp gene responsible for multiple antibiotic resistance by regulating the AcrAB-TolC pump, predominantly originating from China. Additionally, a distinct MDR ST42(1/11) strain with an ICE on chromosome was also identified. Furthermore, phylogenetic analysis of global ST42/ST2814 isolates highlighted the regional specificity of these strains, with Jiangsu isolates clustering together with domestic isolates and XDR ST2814 forming a distinct branch, suggesting adaptation to local antibiotic pressures. Conclusions: This research underscores the pressing need for closely monitoring the MDR/XDR Salmonella Paratyphi B, particularly the emerging ST2814 strains in Jiangsu Province, to effectively curb its spread and protect public health. Moreover, surveillance should be strengthened across different ecological niches and genera to track resistance genes and horizontal gene transfer elements under the concept of “ONE HEALTH”.

In the present study, our aim was to assess the effect of dietary black soldier fly oil (BSFO) with different lipid contents on the growth performance, body composition, lipid metabolism, and related gene expression in juvenile mirror carp (Cyprinus carpio var. specularis). An 8-week feeding trial was conducted using four isonitrogenous diets (32.0% crude protein) containing two lipid levels: 6% (control (CT) group) and 9% (high lipid (HL) group), both using soybean oil as the oil source. The other two diets contained BSFO on the basis of 6% and 9% lipid, referred to as (CT + BSFO) and (HL + BSFO) groups. The results showed that final body weight, weight gain rate, specific growth rate, protein retention ratio, and feed utilization were significantly increased by using higher dietary lipid levels (P

Abstract Poyang Lake is an essential natural wetland in the Yangtze River basin and plays a vital role in maintaining the ecosystem function and ecological security in the middle and lower reaches of the Yangtze River. However, the relative importance and spatial heterogeneity of the impacts of human activities and land use changes on ecological security needs to be further explored. Here, we analyzed the habitat quality level around Poyang Lake in 2022 and explored the factors of habitat quality change from a geographical perspective. The land use structure changes around the Poyang Lake basin from 2000 to 2022 were quantitatively analyzed, and then the relative importance and spatial heterogeneity of each factor on ecological security changes were investigated using geographic probes. The results show that (1) The worst quality habitat (0–0.1) consists mainly of construction land (1624.9 km2) with an area of 1634.64 km2; (2) Construction land continues to increase with the most significant change, and the dynamic land use attitude is 0.47. Grassland and mudflats have the greatest decrease. The increase in cultivated land in different periods is mainly due to the shift of water surface and forest land; (3) The drivers of habitat quality in Poyang Lake were significantly influenced by the interaction of socioeconomic factors. The explanatory power of population density interacting with the total year‐end population and population density interacting with administrative area exceeded 0.84. These values were higher than the explanatory power of each individual factor, indicating that habitat quality was primarily associated with population density, total year‐end population, and administrative area. These results suggest that human activities contribute to the degradation of wetlands around Poyang Lake. This study has significant reference value for coordinating human–land relationships in Poyang Lake, optimizing land management policy, and improving the sustainable development of cities.

Due to the wide usage of high-carbohydrate diets in aquaculture, improving the ability of fish to utilize high-carbohydrate diets is one of the important issues in aquaculture. Adipose tissue is an essential organ for storing energy and plays a vital role in glucose homeostasis. In this study, RNA sequencing reveals that docosahexaenoic acid (DHA) promoted the expression of the glucose metabolism related-genes in grass carp adipocytes, raising the hypothesis that DHA may attenuate the adverse effect of high-carbohydrate diets on fish via promoting glucose metabolism in adipose tissue. To verify this hypothesis, a total of 180 juvenile grass carp (14.24 ± 0.43 g) and a total of 180 largemouth bass (40.03 ± 0.12 g) were randomly distributed into 18 tanks (200 L), respectively, and fed with high-carbohydrate diets containing DHA. The results showed that high-carbohydrate diets promoted glycolysis and inhibited lipolysis and fatty acid β-oxidation, leading to the excessive accumulation of abdominal fat and adipose tissue inflammation. After feeding high-carbohydrate diets supplementation with DHA, glucose transporter type 4 (GLUT4) mediated-glucose uptake was increased in adipose tissue, resulting in significantly decreased blood glucose in grass carp and largemouth bass (P

Abstract To improve the hospital's ability to proactively detect infectious diseases, a knowledge-based infectious disease monitoring and decision support system was established based on real medical records and knowledge rules. The effectiveness of the system was evaluated using interrupted time series analysis. In the system, a monitoring and alert rule library for infectious diseases was generated by combining infectious disease diagnosis guidelines with literature and a real medical record knowledge map. The system was integrated with the electronic medical record system, and doctors were provided with various types of real-time warning prompts when writing medical records. The effectiveness of the system's alerts was analyzed from the perspectives of false positive rates, rule accuracy, alert effectiveness, and missed case rates using interrupted time series analysis. Over a period of 12 months, the system analyzed 4,497,091 medical records, triggering a total of 12,027 monitoring alerts. Of these, 98.43% were clinically effective, while 1.56% were invalid alerts, mainly owing to the relatively rough rules generated by the guidelines leading to several false alarms. In addition, the effectiveness of the system's alerts, distribution of diagnosis times, and reporting efficiency of doctors were analyzed. 89.26% of infectious disease cases could be confirmed and reported by doctors within 5 min of receiving the alert, and 77.6% of doctors could complete the filling of 33 items of information within 2 min, which is a reduction in time compared to the past. The timely reminders from the system reduced the rate of missed cases by doctors; the analysis using interrupted time series method showed an average reduction of 4.4037% in the missed-case rate. This study proposed a knowledge-based infectious disease decision support system based on real medical records and knowledge rules, and its effectiveness was verified. The system improved the management of infectious diseases, increased the reliability of decision-making, and reduced the rate of underreporting.

Abstract Nirsevimab is a monoclonal antibody that binds to the respiratory syncytial virus (RSV) fusion protein. During the Phase 2b (NCT02878330) and MELODY (NCT03979313) clinical trials, infants received one dose of nirsevimab or placebo before their first RSV season. In this pre-specified analysis, isolates from RSV infections were subtyped, sequenced and analyzed for nirsevimab binding site substitutions; subsequently, recombinant RSVs were engineered for microneutralization susceptibility testing. Here we show that the frequency of infections caused by subtypes A and B is similar across and within the two trials. In addition, RSV A had one and RSV B had 10 fusion protein substitutions occurring at >5% frequency. Notably, RSV B binding site substitutions were rare, except for the highly prevalent I206M:Q209R, which increases nirsevimab susceptibility; RSV B isolates from two participants had binding site substitutions that reduce nirsevimab susceptibility. Overall, >99% of isolates from the Phase 2b and MELODY trials retained susceptibility to nirsevimab.

Abstract Aim To explore relationships among disease knowledge, social support, anxiety and self‐efficacy in patients after total knee arthroplasty (TKA) through a chain mediating model. Design A cross‐sectional study. Methods A total of 282 post‐TKA patients from three tertiary hospitals in Jinan, Shandong Province are conveniently chosen as the subjects of this study. We use established scales to assess relevant variables and apply the PROCESS 3.5 software of SPSS to construct a chain mediating effect. Results The results of this study found that disease knowledge can directly affect patients' self‐efficacy (β = 0.466, t = 5.227, p

Abstract Rumination is a cognitive style characterized by repetitive thoughts about one’s negative internal states and is a common symptom of depression. Previous studies have linked trait rumination to alterations in the default mode network, but predictive brain markers of rumination are lacking. Here, we adopt a predictive modeling approach to develop a neuroimaging marker of rumination based on the variance of dynamic resting-state functional connectivity and test it across 5 diverse subclinical and clinical samples (total n = 288). A whole-brain marker based on dynamic connectivity with the dorsomedial prefrontal cortex (dmPFC) emerges as generalizable across the subclinical datasets. A refined marker consisting of the most important features from a virtual lesion analysis further predicts depression scores of adults with major depressive disorder (n = 35). This study highlights the role of the dmPFC in trait rumination and provides a dynamic functional connectivity marker for rumination.

Docosahexaenoic acid (DHA) is a biologically active fatty acid that reduces the accumulation of lipids. However, the molecular mechanism underlying this process, particularly in fish, is not well understood. Recent studies show that endoplasmic reticulum (ER) stress triggers the activation of the unfolded protein response, which has been revealed to play an essential role in lipid metabolism. In this study, we explored the effect of DHA on ER stress and investigated the potential molecular mechanisms underlying DHA-induced adipocyte lipolysis in grass carp (Ctenopharyngodon idella) both in vivo and in vitro. We found that DHA remarkably reduced the triglyceride content, increased the secretion of glycerol, promoted lipolysis in adipocytes and evoked ER stress, whereas inhibiting ER stress using 4-phenyl butyric acid (4-PBA) inhibited the effects of DHA (P

OBJECTIVES/GOALS: Hypertension is a major risk factor for coronavirus disease 2019 (COVID-19) severity. Our goal was to determine if hypertension worsens lung pathology induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in hamsters. METHODS/STUDY POPULATION: Male hamsters (7-8 weeks old) were infused with angiotensin II (AII; 200 ng/kg/min via osmotic minipump) for 4 weeks to induce hypertension. During the last week of the infusion, the hamsters were inoculated intranasally with vehicle (V) or SARS-CoV-2 (S; 1 x 105 plaque forming units/ml). Half of the hamsters were sacrificed 1 day post-inoculation (dpi-1) and the other half on dpi-6. Two scoring systems were applied to lung tissue sections stained with hematoxylin and eosin to determine the degree and severity of lung pathology: the first system assessed all pertinent alterations in the lungs, while the second system only assessed the pathology related to the pulmonary vasculature. Lung histopathology scores were calculated as the sum of the airway and lung alveolar scores in arbitrary units (AU). RESULTS/ANTICIPATED RESULTS: Studies revealed that the SARS-CoV-2-infected hamsters exhibited a 76-fold higher total airway score compared to vehicle controls [(AU): V, 0.25 ± 0.1; S, 19.00 ±1.35; p

OBJECTIVES/GOALS: In the U.S., over 4 million people including children experience transient periods of undernutrition annually. Cardio-metabolic and renal diseases are more prevalent in this population. We are investigating therapeutic strategies to reverse the long-term risk of these diseases in a rat model of transient undernutrition followed by refeeding. METHODS/STUDY POPULATION: Thirty six female Fischer rats (3-months of age) were initially divided into 2 groups. Half were fed regular chow (CT) while the other half were severely food restricted (sFR) by 60% from 0-2 weeks (wks) followed by refeeding from 2-14 wks (sFR-Refed). These 2 groups were then subdivided and treated ± metformin (Met) from wk 7 to wk 12 (n=9/group). High precision ultrasound was conducted on live rats to assess heart and kidney function immediately after the sFR period ended (wk 2) and at the end of the study (wk 14). At the conclusion of the experiment, the rats were sacrificed and the histology of the kidney and heart tissues were analyzed in hematoxylin and eosin-stained sections. The protein to DNA ratio was also calculated in homogenates from these tissues. RESULTS/ANTICIPATED RESULTS: In sFR-Refed rats, cardiac output (CO), heart rate (HR) and renal artery blood flow (RBF) were decreased by 11 ± 1.5%#, 7.0 ± 6.0% and 22 ± 0.6%#, respectively, compared to control (CT) rats; #p

Cold exposure exerts negative effects on hippocampal nerve development in adolescent mice, but the underlying mechanisms are not fully understood. Given that ubiquitination is essential for neurodevelopmental processes, we attempted to investigate the effects of cold exposure on the hippocampus from the perspective of ubiquitination. By conducting a ubiquitinome analysis, we found that cold exposure caused changes in the ubiquitination levels of a variety of synaptic-associated proteins. We validated changes in postsynaptic density-95 (PSD-95) ubiquitination levels by immunoprecipitation, revealing reductions in both the K48 and K63 polyubiquitination levels of PSD-95. Golgi staining further demonstrated that cold exposure decreased the dendritic-spine density in the CA1 and CA3 regions of the hippocampus. Additionally, bioinformatics analysis revealed that differentially ubiquitinated proteins were enriched in the glycolytic, hypoxia-inducible factor-1 (HIF-1), and 5‘-monophosphate (AMP)-activated protein kinase (AMPK) pathways. Protein expression analysis confirmed that cold exposure activated the mammalian target of rapamycin (mTOR)/HIF-1α pathway. We also observed suppression of pyruvate kinase M2 (PKM2) protein levels and the pyruvate kinase (PK) activity induced by cold exposure. Regarding oxidative phosphorylation, a dramatic decrease in mitochondrial respiratory-complex I activity was observed, along with reduced gene expression of the key subunits NADH: ubiquinone oxidoreductase core subunit V1 (Ndufv1) and Ndufv2. In summary, cold exposure negatively affects hippocampal neurodevelopment and causes abnormalities in energy homeostasis within the hippocampus.

Abstract The 2022 Winter Olympics were held in the three competition zones of Beijing, Yanqing and Zhangjiakou, China. The venues of this Winter Olympics were scattered and the terrain was complex. Moreover, the medical resources of Hebei and Beijing were relatively unbalanced. In the medical security of major events, the connection between first aid and in-hospital processes is of the utmost importance to rescue quality. 5th generation mobile network (5G) applications in medical scenarios are on the rise. It would be of great relevance to fully use 5G’s low-latency and high-speed features to share the process information of patients, ambulance personnel, and the destination hospital’s rescue team at emergency scenes and in transportation, improving rescue efficiency. This paper proposes a system scheme of cross-institutional emergency health information sharing based on 5G and augmented reality wearable devices. It also integrates the construction method of monitoring and other sign data sharing, in addition to testing the proposed scheme’s service quality in 5G environments. In the deployment area of the 5G emergency medical rescue information sharing scheme for the Beijing Winter Olympic Games, we selected two designated medical support institutions for testing. The test adopted a combination of fixed-point and driving tests to experiment on the service data, voice service, and streaming media indicators. The 5G signal's coverage rate was close to 100%, the standalone connection's success rate was 100%, and the drop rate was 0. The average downlink rate of multiple scenarios was 620mbps, and the average uplink rate of 5G was over 71.8mbps, which is higher than the average 5G level in China. The downlink rate was more than 20 times larger than the 4th generation mobile network (4G) rate. This study’s proposed scheme demonstrates the importance of 5G applications in emergency response and support, in addition to providing a suitable scheme for the integration of 5G networks in the medical scene.

Abstract Background Tuberculosis is a dangerous infectious disease with the largest number of reported cases in China every year. Preventing missed diagnosis has an important impact on the prevention, treatment, and recovery of tuberculosis. The earliest pulmonary tuberculosis prediction models mainly used traditional image data combined with neural network models. However, a single data source tends to miss important information, such as primary symptoms and laboratory test results, that is available in multi-source data like medical records and tests. In this study, we propose a multi-stream integrated pulmonary tuberculosis diagnosis model based on structured and unstructured multi-source data from electronic health records. With the limited number of lung specialists and the high prevalence of tuberculosis, the application of this auxiliary diagnosis model can make substantial contributions to clinical settings. Methods The subjects were patients at the respiratory department and infectious cases department of a large comprehensive hospital in China between 2015 to 2020. A total of 95,294 medical records were selected through a quality control process. Each record contains structured and unstructured data. First, numerical expressions of features for structured data were created. Then, feature engineering was performed through decision tree model, random forest, and GBDT. Features were included in the feature exclusion set as per their weights in descending order. When the importance of the set was higher than 0.7, this process was concluded. Finally, the contained features were used for model training. In addition, the unstructured free-text data was segmented at the character level and input into the model after indexing. Tuberculosis prediction was conducted through a multi-stream integration tuberculosis diagnosis model (MSI-PTDM), and the evaluation indices of accuracy, AUC, sensitivity, and specificity were compared against the prediction results of XGBoost, Text-CNN, Random Forest, SVM, and so on. Results Through a variety of characteristic engineering methods, 20 characteristic factors, such as main complaint hemoptysis, cough, and test erythrocyte sedimentation rate, were selected, and the influencing factors were analyzed using the Chinese diagnostic standard of pulmonary tuberculosis. The area under the curve values for MSI-PTDM, XGBoost, Text-CNN, RF, and SVM were 0.9858, 0.9571, 0.9486, 0.9428, and 0.9429, respectively. The sensitivity, specificity, and accuracy of MSI-PTDM were 93.18%, 96.96%, and 96.96%, respectively. The MSI-PTDM prediction model was installed at a doctor workstation and operated in a real clinic environment for 4 months. A total of 692,949 patients were monitored, including 484 patients with confirmed pulmonary tuberculosis. The model predicted 440 cases of pulmonary tuberculosis. The positive sample recognition rate was 90.91%, the false-positive rate was 9.09%, the negative sample recognition rate was 96.17%, and the false-negative rate was 3.83%. Conclusions MSI-PTDM can process sparse data, dense data, and unstructured text data concurrently. The model adds a feature domain vector embedding the medical sparse features, and the single-valued sparse vectors are represented by multi-dimensional dense hidden vectors, which not only enhances the feature expression but also alleviates the side effects of sparsity on the model training. However, there may be information loss when features are extracted from text, and adding the processing of original unstructured text makes up for the error within the above process to a certain extent, so that the model can learn data more comprehensively and effectively. In addition, MSI-PTDM also allows interaction between features, considers the combination effect between patient features, adds more complex nonlinear calculation considerations, and improves the learning ability of the model. It has been verified using a test set and via deployment within an actual outpatient environment.

In order to find viable alternative protein sources for aquaculture, we evaluated the effect of partial or complete replacement of dietary soybean meal with yellow mealworm (TM) on the flesh quality of grass carp. In this study, 180 grass carp (511.85 ± 0.25 g) were fed 3 experimental diets in which 0% (CN), 30% (YM30) and 100% (YM100) dietary soybean meal was replaced by TM for 90 d. The results showed that growth performance, biological parameters and serum antioxidant capacity of grass carp were not affected by dietary TM (P > 0.05). Both muscle and whole body crude protein were obviously promoted with the increase of dietary TM (P 0.05), indicating that food safety was not influenced by TM. Dietary TM improved muscle textural characteristics by elevating adhesiveness, springiness and chewiness in YM100 (P

IntroductionNirsevimab is an extended half-life (M252Y/S254T/T256E [YTE]-modified) monoclonal antibody to the pre-fusion conformation of the respiratory syncytial virus (RSV) Fusion protein, with established efficacy in preventing RSV-associated lower respiratory tract infection in infants for the duration of a typical RSV season. Previous studies suggest that nirsevimab confers protection via direct virus neutralization. Here we use preclinical models to explore whether fragment crystallizable (Fc)-mediated effector functions contribute to nirsevimab-mediated protection.MethodsNirsevimab, MEDI8897* (i.e., nirsevimab without the YTE modification), and MEDI8897*-TM (i.e., MEDI8897* without Fc effector functions) binding to Fc γ receptors (FcγRs) was evaluated using surface plasmon resonance. Antibody-dependent neutrophil phagocytosis (ADNP), antibody-dependent cellular phagocytosis (ADCP), antibody-dependent complement deposition (ADCD), and antibody-dependent cellular cytotoxicity (ADCC) were assessed through in vitro and ex vivo serological analyses. A cotton rat challenge study was performed with MEDI8897* and MEDI8897*-TM to explore whether Fc effector functions contribute to protection from RSV.ResultsNirsevimab and MEDI8897* exhibited binding to a range of FcγRs, with expected reductions in FcγR binding affinities observed for MEDI8897*-TM. Nirsevimab exhibited in vitro ADNP, ADCP, ADCD, and ADCC activity above background levels, and similar ADNP, ADCP, and ADCD activity to palivizumab. Nirsevimab administration increased ex vivo ADNP, ADCP, and ADCD activity in participant serum from the MELODY study (NCT03979313). However, ADCC levels remained similar between nirsevimab and placebo. MEDI8897* and MEDI8897*-TM exhibited similar dose-dependent reduction in lung and nasal turbinate RSV titers in the cotton rat model.ConclusionNirsevimab possesses Fc effector activity comparable with the current standard of care, palivizumab. However, despite possessing the capacity for Fc effector activity, data from RSV challenge experiments illustrate that nirsevimab-mediated protection is primarily dependent on direct virus neutralization.

This paper investigates the selection of voxels for functional Magnetic Resonance Imaging (fMRI) brain data. We aim to identify a comprehensive set of discriminative voxels associated with human learning when exposed to a neutral visual stimulus that predicts an aversive outcome. However, due to the nature of the unconditioned stimuli (typically a noxious stimulus), it is challenging to obtain sufficient sample sizes for psychological experiments, given the tolerability of the subjects and ethical considerations. We propose a stable hierarchical voting (SHV) mechanism based on stability selection to address this challenge. This mechanism enables us to evaluate the quality of spatial random sampling and minimizes the risk of false and missed detections. We assess the performance of the proposed algorithm using simulated and publicly available datasets. The experiments demonstrate that the regularization strategy choice significantly affects the results' interpretability. When applying our algorithm to our collected fMRI dataset, it successfully identifies sparse and closely related patterns across subjects and displays stable weight maps for three experimental phases under the fear conditioning paradigm. These findings strongly support the causal role of aversive conditioning in altering visual-cortical activity.

Abstract Background Sturge Weber syndrome (SWS), can cause extensive capillary malformations on the face, head, trunk, and other parts of the body, and the eyes can also suffer optic nerve injury. Secondary glaucoma can cause blindness, which has the characteristics of a relatively hidden onset and unclear pathogenesis. The treatment of SWS secondary glaucoma has always been difficult, and due to the characteristics of the disease, there is uncertainty about the long-term efficacy and safety of various treatment methods for such patients. Methods A total of 105 parents of children with SWS completed a self-designed general information questionnaire, a generalized anxiety questionnaire (GAD-7), a patient health questionnaire (PHQ-2), a stress perception scale (PSS-4), a simple coping scale (SCSQ) and a disease-uncertainty scale (PPUS). Results The total uncertainty score of parents of children with SWS was 79.07 ± 13.24, and the average item score was 2.82 ± 0.47. Multiple linear regression analysis revealed that anxiety and simple coping were the main influencing factors of disease uncertainty among parents of children with SWS (P

Sarcopenia is defined as an age-related decline in muscle mass, muscle strength, and physical performance. Eating alone has been linked to various health issues in older adults. This study investigated the relationship between eating alone and handgrip strength (HGS) in older adults using data from 7278 individuals (≥65 years) who participated in the 2014–2019 Korea National Health and Nutrition Examination Survey. HGS was measured using a digital grip strength dynamometer, relative HGS was calculated by dividing HGS by body mass index, and dynapenia was defined as an HGS < 28 kg for men and

The early prediction of epileptic seizures holds paramount significance in patient care and medical research. Extracting useful spatial-temporal features to facilitate seizure prediction represents a primary challenge in this field. This study proposes GAMRNN, a novel methodology integrating a dual-layer gated recurrent unit (GRU) model with a convolutional attention module. GAMRNN aims to capture intricate spatial-temporal characteristics by highlighting informative feature channels and spatial pattern dynamics. We employ the Lion optimization algorithm to enhance the model's generalization capability and predictive accuracy. Our evaluation of GAMRNN on the widely utilized CHB-MIT EEG dataset demonstrates its effectiveness in seizure prediction. The results include an impressive average classification accuracy of 91.73%, sensitivity of 88.09%, specificity of 92.09%, and a low false positive rate of 0.053/h. Notably, GAMRNN enables early seizure prediction with a lead time ranging from 5 to 35 min, exhibiting remarkable performance improvements compared to similar prediction models.

Objective Putaminal iron deposition is an important feature that helps differentiate multiple system atrophy with predominant parkinsonism (MSA-p) from Parkinson’s disease (PD). Most previous studies used visual inspection or quantitative methods with manual manipulation to perform this differentiation. We investigated the value of a new semiautomated diagnostic algorithm using 3T-MR susceptibility-weighted imaging for MSA-p. Methods This study included 26 MSA-p, 68 PD, and 41 normal control (NC) subjects. The algorithm was developed in 2 steps: 1) determine the image containing the remarkable putaminal margin and 2) calculate the phase-shift values, which reflect the iron concentration. The next step was to identify the best differentiating conditions among several combinations. The highest phase-shift value of each subject was used to assess the most effective diagnostic set. Results The raw phase-shift values were present along the lateral margin of the putamen in each group. It demonstrates an anterior-to-posterior gradient that was identified most frequently in MSA-p. The average of anterior 5 phase shift values were used for normalization. The highest area under the receiver operating characteristic curve (0.874, 80.8% sensitivity, and 86.7% specificity) of MSA-p versus PD was obtained under the combination of 3 or 4 vertical pixels and one dominant side when the normalization methods were applied. In the subanalysis for the MSA-p patients with a longer disease duration, the performance of the algorithm improved. Conclusion This algorithm detected the putaminal lateral margin well, provided insight into the iron distribution of the putaminal rim of MSA-p, and demonstrated good performance in differentiating MSA-p from PD.

Abstract Background A deep convolutional neural network (DCNN) system is proposed to measure the lower limb parameters of the mechanical lateral distal femur angle (mLDFA), medial proximal tibial angle (MPTA), lateral distal tibial angle (LDTA), joint line convergence angle (JLCA), and mechanical axis of the lower limbs. Methods Standing X-rays of 1000 patients’ lower limbs were examined for the DCNN and assigned to training, validation, and test sets. A coarse-to-fine network was employed to locate 20 key landmarks on both limbs that first recognised the regions of hip, knee, and ankle, and subsequently outputted the key points in each sub-region from a full-length X-ray. Finally, information from these key landmark locations was used to calculate the above five parameters. Results The DCNN system showed high consistency (intraclass correlation coefficient > 0.91) for all five lower limb parameters. Additionally, the mean absolute error (MAE) and root mean squared error (RMSE) of all angle predictions were lower than 3° for both the left and right limbs. The MAE of the mechanical axis of the lower limbs was 1.124 mm and 1.416 mm and the RMSE was 1.032 mm and 1.321 mm, for the right and left limbs, respectively. The measurement time of the DCNN system was 1.8 ± 1.3 s, which was significantly shorter than that of experienced radiologists (616.8 ± 48.2 s, t = -180.4, P

Abstract Nasopharyngeal carcinoma (NPC) clinical trials show that antiangiogenic drugs (AADs) fail to achieve the expected efficacy, and combining AAD with chemoradiotherapy does not show superiority over chemoradiotherapy alone. Accumulating evidence suggests the intrinsic AAD resistance in NPC patients with poorly understood molecular mechanisms. Here, we describe NPC-specific FGF-2 expression-triggered, VEGF-independent angiogenesis as a mechanism of AAD resistance. Angiogenic factors screening between AAD-sensitive cancer type and AAD-resistant NPC showed high FGF-2 expression in NPC in both xenograft models and clinical samples. Mechanistically, the FGF-2-FGFR1-MYC axis drove endothelial cell survival and proliferation as an alternative to VEGF-VEGFR2-MYC signaling. Genetic knockdown of FGF-2 in NPC tumor cells reduced tumor angiogenesis, enhanced AAD sensitivity, and reduced pulmonary metastasis. Moreover, lenvatinib, an FDA recently approved multi-kinase inhibitor targeting both VEGFR2 and FGFR1, effectively inhibits the tumor vasculature, and exhibited robust anti-tumor effects in NPC-bearing nude mice and humanized mice compared with an agent equivalent to bevacizumab. These findings provide mechanistic insights on FGF-2 signaling in the modulation of VEGF pathway activation in the NPC microenvironment and propose an effective NPC-targeted therapy by using a clinically available drug.

Composite mantle cell lymphoma and classical Hodgkin lymphoma is very rare and the actual origin of it is still unclear. Here we reported a new case of composite mantle cell lymphoma and classical Hodgkin lymphoma and analyzed its molecular changes. Eight mutations were identified in its Hodgkin component through next-generation sequencing. In addition, we reviewed the published cases of composite mantle cell lymphoma and classical Hodgkin lymphoma and summarized the molecular changes of reported cases as well as the current case to explore the possible pathway of histogenesis.

Coumarin derivatives have diverse structures and show various significant biological activities. Aiming to develop more potent coumarin derivatives for cancer treatment, a series of coumarin acrolein hybrids were designed and synthesized by using molecular hybridization approach, and investigated for their antiproliferative activity against A549, KB, Hela and MCF-7 cancer cells as well as HUVEC and LO2 human normal cells. The results indicated that most of the synthesized compounds displayed remarkable inhibitory activity towards cancer cells but low cytotoxicity on normal cells. Among all the compounds, 5d and 6e were the most promising compounds against different cancer cell lines, especially for A549 and KB cells. The preliminary action mechanism studies suggested that compound 6e, the representative compound, was capable of dose-dependently suppressing migration, invasion and inducing significant apoptosis. Furthermore, the combined results of network pharmacology and validation experiments revealed that compound 6e induced mitochondria dependent apoptosis via the PI3K/AKT-mediated Bcl-2 signaling pathway. In summary, our study indicated compound 6e could inhibit cell proliferation, migration, invasion and promote cell apoptosis through inhibition of PI3K/AKT signaling pathway in human oral epidermoid carcinoma cells. These findings demonstrated the potential of 3-(coumarin-3-yl)-acrolein derivatives as novel anticancer chemotherapeutic candidates, providing ideas for further development of drugs for clinical use.

Chagan Sag is one of the most significant tectonic unit in the Yin'e Basin. The special component of the organic macerals and biomarkers in the Chagan sag suggests great difference of its hydrocarbon generation process. In this paper, forty samples of source rocks are subjected to carry out on the geochemical characteristics by methods of rock-eval analysis, organic petrology and gas chromatography mass spectrometry (GC-MS) to reveal the origin, depositional environment and maturity of organic matter in Chagan Sag, Yin'e Basin of Inner Mongolia. The total organic matter of the analyzed samples ranges from 0.4 wt%∼3.89 wt% with an average of 1.12 wt%, indicating fair to excellent hydrocarbon generation potential. The rock-eval results show that the S1+S2 and hydrocarbon index range from 0.03 mg/g∼16.34 mg/g (avg.3.6 mg/g) and 6.24–521.32 mg/g (avg. 199.63 mg/g), suggesting most of the kerogen types are type II and III, with small amount of type I. The Tmax ranges from 428 to 496 °C, suggesting low mature to mature stage. The macerals component of morphological macerals presents with certain amount of vitrinite, liptinite and some inertinite. However, the amorphous component takes the dominant part of the macerals with account of 50%–80%. The amorphous components are dominated by sapropelite in the source rock, indicating bacteriolytic amorphous promote the organic generation process. Hopanes and sterane are widely distributed in the source rocks. The biomarker results suggest a mix of planktonic-bacterial and higher plant origins, with wide range of thermal maturity and relatively reducing depositional environment. Abnormal high content of hopanes were observed in the biomarkers, and some special biomarkers such as monomethylalkanes, long-chain-alkyl naphthalenes, aromatized de A-triterpenes, 8,14-seco-triterpenes, and A, B-cyclostane are detected in Chagan Sag. The presence of these compounds suggests that bacterial and microorganisms are of great significance to the generation of hydrocarbon in the source rock in Chagan Sag.

(1) Introduction: Epigenetic changes have been proposed as a biologic link between in-utero exposure to maternal smoking and health outcomes. Therefore, we examined if in-utero exposure to maternal smoking was associated with infant DNA methylation (DNAm) of cytosine-phosphate-guanine dinucleotides (CpG sites) in the arginine vasopressin receptor 1A AVPR1a gene. The AVPR1a gene encodes a receptor that interacts with the arginine vasopressin hormone and may influence physiological stress regulation, blood pressure, and child development. (2) Methods: Fifty-two infants were included in this cohort study. Multivariable linear models were used to examine the effect of in-utero exposure to maternal smoking on the mean DNAm of CpG sites located at AVPR1a. (3) Results: After adjusting the model for substance use, infants with in-utero exposure to maternal smoking had a reduction in DNAm at AVPR1a CpG sites by −0.02 (95% CI −0.03, −0.01) at one month of age. In conclusion, in-utero exposure to tobacco smoke can lead to differential patterns of DNAm of AVPR1a among infants. Conclusions: Future studies are needed to identify how gene expression in response to early environmental exposures contributes to health outcomes.

Abstract Background Modernizing medical education by using artificial intelligence and other new technologies to improve the clinical thinking ability of medical students is an important research topic in recent years. Prominent medical universities are actively conducting research and exploration in this area. In particular, given the shortage of human resources, the need to maintain social distancing to prevent the spread of the epidemics, and the increase in the cost of medical education, it is critical to harness online learning to promote medical education. A virtual case learning system that uses natural language processing technology to process and present a hospital’s real medical records and evaluate student responses can effectively improve medical students’ clinical thinking abilities. Objective The purpose of this study is to develop a virtual case system, AIteach, based on actual complete hospital medical records and natural language processing technology, and achieve clinical thinking ability improvement through a contactless, self-service, trial-and-error system application. Methods Case extraction is performed on a hospital’s case data center and the best-matching cases are produced through natural language processing, word segmentation, synonym conversion, and sorting. A standard clinical questioning data module, virtual case data module, and student learning difficulty module are established to achieve simulation. Students can view the objective examination and inspection data of actual cases, including details of the consultation and physical examination, and automatically provide their learning response via a multi-dimensional evaluation system. In order to assess the changes in students’ clinical thinking after using AIteach, 15 medical graduate students were subjected to two simulation tests before and after learning through the virtual case system. The tests, which included the full-process case examination of cases having the same difficulty level, examined core clinical thinking test points such as consultation, physical examination, and disposal, and generated multi-dimensional evaluation indicators (rigor, logic, system, agility, and knowledge expansion). Thus, a complete and credible evaluation system is developed. Results The AIteach system used an internal and external double-cycle learning model. Students collect case information through online inquiries, physical examinations, and other means, analyze the information for feedback verification, and generate their detailed multi-dimensional clinical thinking after learning. The feedback report can be evaluated and its knowledge gaps analyzed. Such learning based on real cases is in line with traditional methods of disease diagnosis and treatment, and addresses the practical difficulties in reflecting actual disease progression while keeping pace with recent research. Test results regarding short-term learning showed that the average score (P

Background: Understanding the transmissibility and pathogenicity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is crucial for control policies, but evidence remains limited. Methods: We presented a systematic and meta-analytic summary concerning the transmissibility and pathogenicity of COVID-19. Results: A total of 105 studies were identified, with 35042 infected cases and 897912 close contacts. 48.6% (51/105) of studies on secondary transmissions were from China. We estimated a total SIR of 7.8% (95% confidence interval [CI], 6.8%−8.8%), SAR of 6.6% (95% CI, 5.7%−7.5%), and symptomatic infection ratio of 86.9% (95%CI, 83.9%−89.9%) with a disease series interval of 5.84 (95%CI, 4.92–6.94) days. Household contacts had a higher risk of both symptomatic and asymptomatic infection, and transmission was driven between index cases and second-generation cases, with little transmission occurring in second-to-later-generation cases (SIR, 12.4% vs. 3.6%). The symptomatic infection ratio was not significantly different in terms of infection time, generation, type of contact, and index cases. Conclusions: Our results suggest a higher risk of infection among household contacts. Transmissibility decreased with generations during the intervention. Pathogenicity of SARS-CoV-2 varied among territories, but didn’t change over time. Strict isolation and medical observation measures should be implemented.

Highlights What are the long-term effects of a 2-week period of severe food restriction (sFR) on cardiac structure and function months after refeeding (sFR-Refed) in male and female rats? This study shows sex differences exist in cardiac pathology months after refeeding. A majority of cardiomyocytes were atrophied in F-sFR-Refed rats, while in M-sFR-Refed rats, the cardiomyocytes predominantly exhibited hypertrophic remodeling. While there were no differences in the frequency of ventricular arrhythmias induced by ischemia/reperfusion (I/R) in the isolated heart between M-CT and M-sFR-Refed rats, I/R induced twice as many arrhythmias in the F-sFR-Refed rats compared to the controls. Our findings have implications for the long-term risk of developing cardiovascular disease in individuals who have voluntarily or involuntarily experienced periods of sFR earlier in their lives, and that woman may be at greater cardiovascular risk than men.

In recent years, high-fat diet (HFD) has been widely applied in aquaculture, which reduces the intestinal health of cultured fish. The current study evaluated the protective effects of nano-selenium (nano-Se) on intestinal health of juvenile grass carp (Ctenopharyngodon idella) fed with HFD. A total of 135 experimental fish were fed with a regular diet (Con), a HFD (HFD) and a HFD containing nano-Se at 0.6 mg/kg (HSe) for 10 weeks. The results showed that dietary nano-Se significantly improved the survival rate and feed efficiency which were reduced by HFD in juvenile grass carp (P