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Deconvolution is a commonly employed technique for enhancing image quality in optical imaging methods. Unfortunately, its application in optical coherence tomography (OCT) is often hindered by sensitivity to noise, which leads to additive ringing artifacts. These artifacts considerably degrade the quality of deconvolved images, thereby limiting its effectiveness in OCT imaging. In this study, we propose a framework that integrates numerical random phase masks into the deconvolution process, effectively eliminating these artifacts and enhancing image clarity. The optimized joint operation of an iterative Richardson-Lucy deconvolution and numerical synthesis of random phase masks (RPM), termed as Deconv-RPM, enables a 2.5-fold reduction in full width at half-maximum (FWHM). We demonstrate that the Deconv-RPM method significantly enhances image clarity, allowing for the discernment of previously unresolved cellular-level details in nonkeratinized epithelial cells ex vivo and moving blood cells in vivo.

Abstract Background To compare the early clinical efficacy of percutaneous endoscopic posterior lumbar interbody fusion (PE-PLIF) and modified posterior lumbar interbody fusion (MPLIF) in the treatment of lumbar degenerative disease (LDD). Methods A total of 37 patients who underwent PE-PLIF and 58 patients who underwent MPLIF from March 2019 to January 2022 were retrospectively reviewed. The operation time, intraoperative blood loss, post-operative hospitalization time, and post-operative bedrest time were recorded. The visual analogue scale (VAS) scores of leg pain and low back pain, Japanese Orthopaedic Association (JOA) scores, and the Oswestry Disability Index (ODI) scores were evaluated and compared before the operation, 3 days after the operation, 1 week after the operation, 1 month after the operation, 6 months after the operation and at the last follow-up. The modified MacNab’s criteria were applied at the last follow-up. The fusion rate and surgical-related complications during follow-up were recorded. Results The average operation time in the PE-PLIF group was highly significant longer than that in the MPLIF group (P

To investigate the impact of sulfate corrosion on the performance of shaft lining concrete under sustained compressive loads, this study immersed samples in a 10 % sodium sulfate solution after subjecting to sustained compressive loads of 0.2fcand 0.4fc. The variation in compressive strength, ultrasonic velocity, and dynamic elasticity modulus with corrosion age were examined. The corrosion mechanisms were analyzed using field emission scanning electron microscope and energy dispersive spectrometer. The impact tendency of concrete was also evaluated. The results indicated that under sustained compressive loads of 0.2fcand 0.4fc, the compressive strength, ultrasonic velocity, and dynamic elasticity modulus are all increased with age, in the order of 0.2fc> 0.4fc>no-load. When exposed to a 10 % sodium sulfate solution under sustained compressive loads, these properties initially increased and then decreased, peaking at 90 days of corrosion age, and the order was 0.2fc> no-load > 0.4fc when the corrosion age was longer than 240 days.The shaft lining concrete exhibited weak impact tendency, with the brittleness index increasing as the corrosion age progressed. The outcome of this work might provide a reference for the further research on the design of shaft lining concrete materials.

Backgroud Bronchopulmonary dysplasia (BPD) is one of the most important complications plaguing neonates and can lead to a variety of sequelae. the ability of the HIF-1α/VEGF signaling pathway to promote angiogenesis has an important role in neonatal lung development.Method Newborn rats were exposed to 85% oxygen. The effects of hyperoxia exposure on Pleomorphic Adenoma Gene like-2 (PLAGL2) and the HIF-1α/VEGF pathway in rats lung tissue were assessed through immunofluorescence and Western Blot analysis. In cell experiments, PLAGL2 was upregulated, and the effects of hyperoxia and PLAGL2 on cell viability were evaluated using scratch assays, CCK-8 assays, and EDU staining. The role of upregulated PLAGL2 in the HIF-1α/VEGF pathway was determined by Western Blot and RT–PCR. Apoptosis and ferroptosis effects were determined through flow cytometry and viability assays.Results Compared with the control group, the expression levels of PLAGL2, HIF-1α, VEGF, and SPC in lung tissues after 3, 7, and 14 days of hyperoxia exposure were all decreased. Furthermore, hyperoxia also inhibited the proliferation and motility of type II alveolar epithelial cells (AECII) and induced apoptosis in AECII. Upregulation of PLAGL2 restored the proliferation and motility of AECII and suppressed cell apoptosis and ferroptosis, while the HIF-1α/VEGF signaling pathway was also revived.Conclusions We confirmed the positive role of PLAGL2 and HIF-1α/VEGF signaling pathway in promoting BPD in hyperoxia conditions, and provided a promising therapeutic targets.

CagA is a significant oncogenic factor injected into host cells by Helicobacter pylori, which is divided into two subtypes: East Asian type (CagAE), characterized by the EPIYA-D motif, and western type (CagAW), harboring the EPIYA-C motif. CagAE has been reported to have higher carcinogenicity than CagAW, although the underlying reason is not fully understood. SHIP2 is an intracellular phosphatase that can be recruited by CagA to perturb the homeostasis of intracellular signaling pathways. In this study, we found that SHIP2 contributes to the higher oncogenicity of CagAE. Co-Immunoprecipitation and Pull-down assays showed that CagAE bind more SHIP2 than CagAW. Immunofluorescence staining showed that a higher amount of SHIP2 recruited by CagAE to the plasma membrane catalyzes the conversion of PI(3,4,5)P3 into PI(3,4)P2. This alteration causes higher activation of Akt signaling, which results in enhanced IL-8 secretion, migration, and invasion of the infected cells. SPR analysis showed that this stronger interaction between CagAE and SHIP2 stems from the higher affinity between the EPIYA-D motif of CagAE and the SH2 domain of SHIP2. Structural analysis revealed the crucial role of the Phe residue at the Y + 5 position in EPIYA-D. After mutating Phe of CagAE into Asp (the corresponding residue in the EPIYA-C motif) or Ala, the activation of downstream Akt signaling was reduced and the malignant transformation of infected cells was alleviated. These findings revealed that CagAE hijacks SHIP2 through its EPIYA-D motif to enhance its carcinogenicity, which provides a better understanding of the higher oncogenic risk of H. pylori CagAE.

Background The M-type phospholipase A2 receptor (PLA2R)-associated primary membranous nephropathy (PMN) is an immune-related disease in adults with increasing morbidity and variable treatment response, in which inflammation may contribute to the multifactorial immunopathogenesis. The relationship between fibrinogen-albumin ratio (FAR), serving as a novel inflammatory biomarker, and PMN is still unclear. Therefore, this study aims to clarify the association between FAR and disease activity and therapy response of PMN.Methods 110 biopsy-proven phospholipase A2 receptor (PLA2R) -associated PMN participants with nephrotic syndrome from January 2017 to December 2021 were recruited in the First Affiliated Hospital of Nanjing Medical University. The independent risk factors of non-remission (NR) and the predictive ability of FAR were explored by Cox regression and receiver-operating characteristic (ROC) curve analysis. According to the optimal cutoff value, study patients were categorized into the low-FAR group (≤the cutoff value) and the high-FAR group (>the cutoff value). Spearman’s correlations were used to examine the associations between FAR and baseline clinicopathological characteristics. Kaplan-Meier method was used to assess the effects of FAR on remission.Results In the entire study cohort, 78 (70.9%) patients reached complete or partial remission (CR or PR). The optimal cutoff value of FAR for predicting the remission outcome (CR + PR) was 0.233. The Kaplan-Meier survival analysis demonstrated that the high-FAR group (>0.233) had a significantly lower probability to achieve CR or PR compared to the low-FAR group (≤0.233) (Log Rank test, p = 0.021). Higher levels of FAR were identified as an independent risk factor for NR, and the high-FAR group was associated with a 2.27 times higher likelihood of NR than the low-FAR group (HR 2.27, 95% CI 1.01, 5.13, p = 0.048). These relationships remained robust with further analysis among calcineurin inhibitors (CNIs)-receivers. In the multivariate Cox regression model, the incidence of NR was 4.00 times higher in the high-FAR group than in the low-FAR group (HR 4.00, 95% CI 1.41, 11.31, p = 0.009). Moreover, ROC analysis revealed the predictive value of FAR for CR or PR with a 0.738 area under curve (AUC), and the AUC of anti-PLA2R Ab was 0.675. When combining FAR and anti-PLA2R Ab, the AUC was boosted to 0.766.Conclusions FAR was significantly correlated with proteinuria and anti-PLA2R Ab in PMN. As an independent risk factor for NR, FAR might serve as a potential inflammation-based prognostic tool for identifying cases with poor treatment response, and the best predictive cutoff value for outcomes was 0.233.

AbstractMicrofluidic technology has emerged as a powerful tool in studying arterial thrombosis, allowing researchers to construct artificial blood vessels and replicate the hemodynamics of blood flow. This technology has led to significant advancements in understanding thrombosis and platelet adhesion and aggregation. Microfluidic models have various types and functions, and by studying the fabrication methods and working principles of microfluidic chips, applicable methods can be selected according to specific needs. The rapid development of microfluidic integrated system and modular microfluidic system makes arterial thrombosis research more diversified and automated, but its standardization still needs to be solved urgently. One key advantage of microfluidic technology is the ability to precisely control fluid flow in microchannels and to analyze platelet behavior under different shear forces and flow rates. This allows researchers to study the physiological and pathological processes of blood flow, shedding light on the underlying mechanisms of arterial thrombosis. In conclusion, microfluidic technology has revolutionized the study of arterial thrombosis by enabling the construction of artificial blood vessels and accurately reproducing hemodynamics. In the future, microfluidics will place greater emphasis on versatility and automation, holding great promise for advancing antithrombotic therapeutic and prophylactic measures.

Abstract Migrasomes represent a recently uncovered category of extracellular microvesicles, spanning a diameter range of 500 to 3000 nm. They are emitted by migrating cells and harbour a diverse array of RNAs and proteins. Migrasomes can be readily identified in bodily fluids like serum and urine, rendering them a valuable non‐invasive source for disease diagnosis through liquid biopsy. In this investigation, we introduce a streamlined and effective approach for the capture and quantitative assessment of migrasomes, employing wheat germ agglutinin (WGA)‐coated magnetic beads and flow cytometry (referred to as WBFC). Subsequently, we examined the levels of migrasomes in the urine of kidney disease (KD) patients with podocyte injury and healthy volunteers using WBFC. The outcomes unveiled a substantial increase in urinary podocyte‐derived migrasome concentrations among individuals with KD with podocyte injury compared to the healthy counterparts. Notably, the urinary podocyte‐derived migrasomes were found to express an abundant quantity of phospholipase A2 receptor (PLA2R) proteins. The presence of PLA2R proteins in these migrasomes holds promise for serving as a natural antigen for the quantification of autoantibodies against PLA2R in the serum of patients afflicted by membranous nephropathy. Consequently, our study not only pioneers a novel technique for the isolation and quantification of migrasomes but also underscores the potential of urinary migrasomes as a promising biomarker for the early diagnosis of KD with podocyte injury.

The increasingly frequent occurrence of urban heatwaves has become a significant threat to human health. To quantitatively analyze changes in heatwave characteristics and to investigate the return periods of future heatwaves in Wuhan City, China, this study extracted 9 heatwave definitions and divided them into 3 mortality risk levels to identify and analyze historical observations and future projections of heatwaves. The copula functions were employed to derive the joint distribution of heatwave severity and duration and to analyze the co-occurrence return periods. The results demonstrate the following. (1) As the concentration of greenhouse gas emissions increases, the severity of heatwaves intensifies, and the occurrence of heatwaves increases significantly; moreover, a longer duration of heatwaves correlated with higher risk levels in each emission scenario. (2) Increasing concentrations of greenhouse gas emissions result in significantly shorter heatwave co-occurrence return periods at each level of risk. (3) In the 3 risk levels under each emission scenario, the co-occurrence return periods for heatwaves become longer as heatwave severity intensifies and duration increases. Under the influence of climate change, regional-specific early warning systems for heatwaves are necessary and crucial for policymakers to reduce heat-related mortality risks in the population, especially among vulnerable groups.

Preservation of cultural relics is crucial for cultural sustainability, particularly in the case of cave temples, which are a unique and immovable part of our heritage, nested within mountains. These structures bear immense historical significance and possess considerable economic value, making them vulnerable to criminal activities, notably theft. Establishing a robust physical protection system (PPS) is imperative to safeguard these relics from potential damage. This paper proposes a novel approach for assessing the vulnerability of cave temples' PPS. Based on the fuzzy Petri net (FPN) principle, a comprehensive vulnerability assessment index system was developed within the PPS framework, considering the unique characteristics of cave temples. This study refines the formal definition of the FPN, enhancing its precision and effectiveness for vulnerability assessment. The practicality and effectiveness of the proposed method are verified through simulation experiments. An illustrative example is provided to demonstrate this approach.

Introduction: Ilex pubescens (IPES), a traditional Chinese herb widely used in cardiovascular diseases, has shown potential anti-inflammatory capabilities in myocardial infarction. Reactive Oxygen Species (ROS) and the NOD-like Receptor Protein 3 (NLRP3) pathway are significant contributors to aseptic inflammation in heart diseases. This study aims to elucidate the primary mechanism by which IPES inhibits pyroptosis post-myocardial infarction. Methods: By ligating the left coronary artery in C57BL/6 mice, a myocardial infarction model was established to be conducted in vivo. To establish pyroptosis in vitro, primary neonatal cardiomyocytes, extracted from the hearts of Sprague-Dawley rats, were treated in an oxygen-glucose deprivation way. ROS scavenger, NLRP3 inhibitor, and NLRP3 was overexpressed by adenovirus to confirm IPES inhibiting myocardial pyroptosis through the ROS/NLRP3 pathway. Results: In vivo, IPES exerted significant cardioprotective effects, as evidenced by reducing heart injury, improving cardiac function, and decreasing serum markers of cardiac damage. Furthermore, IPES treatment significantly inhibits ROS generation and reduces the expression levels of NLRP3 and its downstream pyroptosis-related proteins. In vitro, IPES therapy significantly decreased cell damage and pyroptosis in a concentration-dependent manner in an oxygen-glucose deprivation/re-oxygenation (OGD/R) cell model. Additionally, IPES demonstrates synergistic cardiomyocyte protection with the ROS scavenger NAC, whereas its inhibition of pyroptosis is not significantly different from that of the NLRP3 inhibitor. More importantly, the inhibitory impacts of IPES on pyroptosis were partially reversed by NLRP3 overexpression. The active components of IPES exhibit the ability to stably and efficiently bind with NLRP3. Discussion: These results demonstrate that IPES inhibit pyroptosis post-MI by suppressing the ROS/NLRP3 pathway, providing a new insight into its potential application in treating MI.

IntroductionInfection with SARS-CoV-2 begins in the upper respiratory tract and can trigger the production of mucosal spike-specific secretory IgA (sIgA), which provides protection against reinfection. It has been recognized that individuals with high level of nasal spike-specific IgA have a lower risk of reinfection. However, mucosal spike-specific sIgA wanes over time, and different individuals may have various level of spike-specific sIgA and descending kinetics, leading to individual differences in susceptibility to reinfection. A method for detecting spike-specific sIgA in the nasal passage would be valuable for predicting the risk of reinfection so that people at risk can have better preparedness.MethodsIn this study, we describe the development of a colloidal gold-based immunochromatographic (ICT) strip for detecting SARS-CoV-2 Omicron spike-specific sIgA in nasal mucosal lining fluids (NMLFs).ResultsThe ICT strip was designed to detect 0.125 μg or more spike-specific sIgA in 80 μL of NMLFs collected using a nasal swab. Purified nasal sIgA samples from individuals who recently recovered from an Omicron BA.5 infection were used to demonstrate that this ICT strip can specifically detect spike-specific sIgA. The signal levels positively correlated with neutralizing activities against XBB. Subsequent analysis revealed that people with low or undetectable levels of spike-specific sIgA in the nasal passage were more susceptible to SARS-CoV-2 reinfection.ConclusionsThis nasal spike-specific sIgA ICT strip provides a non-invasive, rapid, and convenient method to assess the risk of reinfection for achieving precision preparedness.

In this study, the Pogostemon cablin polysaccharides (PCPs) were heteropolysaccharides with molecular weights of 63.17 kDa and 8.99 kDa, and their total carbohydrate content was 76.17 ± 0.23%, uronic acid content was 19.92 ± 0.42%, and protein content was 1.24 ± 0.07%. PCP is composed of arabinose, galactose, glucose, and glucuronic acid, with a molar ratio of 0.196:0.249:0.451:0.104. In addition, we further investigated the effects of the diet supplemented with different doses of PCP on growth performance, meat quality, and anti-oxidant capacity in Chongren Partridge chickens. A total of 200 chickens were randomly allocated into 4 treatments, and fed with a basal diet of 0 (CON), 200 (LPCP), 400 (MPCP), and 800 (HPCP) mg/kg PCP for a 14-day prefeeding period and a formal experimental period of 56 days. Results showed that dietary PCP significantly increased final body weight (BW), average daily gain (ADG), and decreased feed-to-gain ratio (F/G) from days 1 to 56. Meanwhile, dietary PCP reduced yellowness (b∗) values and increased redness (a∗) values at 24 h in breast muscles (p

Galectins-8 (Gal-8), the tandem repeat sequences of the galectin family, can influence the pathophysiologic processes in neurological disorders. However, its effect on intracerebral hemorrhage and related mechanisms remains nebulous. Using collagenase VII-S-induced ICH in the left striatum of mice, we investigated the effects of Gal-8 on cellular and molecular immune inflammatory responses in hemorrhagic brain and evaluated the severity of short- and long-term brain injury. Our results showed that activated microglia in the periphery of hematoma in mice with intracerebral hemorrhage expressed Gal-8, while Gal-8 could regulate the expression of cytokines, such as HMGB-1 (P = 0.0032), TNF-α (P = 0.0158), and IL-10 (P = 0.0379). Inhibition of the glucose-binding activity of Gal-8 by thiogalactoside (TDG) significantly reduced the volume of cerebral hematoma (P = 0.0241) and hydrocephalus (P = 0.0112) during the acute phase of cerebral hemorrhage and improved the long-term prognosis. TDG can reduce acute-phase brain tissue injury and improve the prognosis by inhibiting the activation of immune-inflammatory cells in the periphery of hematoma and reducing the release of pro-inflammatory factors.

BackgroundRecent studies have indicated an association between sedentary behavior (SB), particularly patterns of SB, and bone health. However, it remains uncertain how different patterns of SB in overweight/obesity older women impact their bone health. This study aimed to investigate the association between objectively measured SB patterns and bone health in Chinese community-dwelling overweight/obesity older women.MethodsCross-sectional data were obtained from a baseline survey of Physical Activity and Health in Older Women Study. Quantitative ultrasound was used to measure speed of sound (SOS), broadband ultrasound attenuation (BUA), bone quality index (BQI) and T value to evaluate bone health. SB patterns were measured using triaxial accelerometers, including sedentary time in SB bouts of ≥ 10, 30, and 60 min, number of SB bouts ≥ 10, 30, and 60 min. Multiple linear regression was used to examine the associations of different SB patterns with bone health.ResultsAfter adjusting for confounders, sedentary time in SB bouts ≥ 60 min, number of SB bouts ≥ 60 min were significantly associated with bone health, with a lower SOS [β = −2.75, 95% confidence interval (CI): −4.96 to −0.53, P = 0.015], BUA (β = −1.20, 95% CI: −2.14 to −0.26, P = 0.013), BQI (β = −1.56, 95% CI: −2.63 to −0.49, P = 0.004), T value (β = −0.08, 95% CI: −0.14 to −0.03, P = 0.004) per 60 min increase of sedentary time in SB bouts ≥ 60 min, and a lower SOS (β = −3.97, 95% CI: −7.54 to −0.40, P = 0.029), BUA (β = −1.80, 95% CI: −3.44 to −0.16, P = 0.031), BQI (β = −2.28, 95% CI: −4.08 to −0.47, P = 0.014) and T value (β = −0.12, 95% CI: −0.22 to −0.03, P = 0.013) per bout increase of SB bouts ≥ 60 min, respectively.ConclusionLimiting the duration of prolonged sedentary bouts and minimizing the occurrence of number of SB bouts ≥ 60 min could be essential in bone health management, especially for those older people who are overweight/obesity.

Background Despite the well-established health benefits of physical activity, a large population of older adults still maintain sedentary life style or physical inactivity. This network meta-analysis (NMA) aimed to compare the effectiveness of wearable activity tracker-based intervention (WAT), electronic and mobile health intervention (E&MH), structured exercise program intervention (SEP), financial incentive intervention (FI) on promoting physical activity and reducing sedentary time in older adults. Methods The systematic review based on PRISMA guidelines, a systematic literature search of PubMed, Web of Science, Google Scholar, EMbase, Cochrane Library, Scopus were searched from inception to December 10 th 2022. The randomized controlled trials (RCT) were included. Two reviewers independently conducted study selection, data extraction, risk of bias and certainty of evidence assessment. The effect measures were standard mean differences (SMD) and 95% confidence interval (CI) in daily steps, moderate-to-vigorous physical activity (MVPA) and sedentary time. Results A total of 69 studies with 14,120 participants were included in the NMA. Among these included studies, the results of daily steps, MVPA and sedentary time was reported by 55, 25 and 15 studies, respectively. The NMA consistency model analysis suggested that the following interventions had the highest probability (surface under the cumulative ranking, SUCRA) of being the best when compared with control: FI + WAT for daily steps (SUCRA = 96.6%; SMD = 1.32, 95% CI:0.77, 1.86), WAT + E&MH + SEP for MVPA (SUCRA = 91.2%; SMD = 0.94, 95% CI: 0.36, 1.52) and WAT + E&MH + SEP for sedentary time (SUCRA = 80.3%; SMD = −0.50, 95% CI: −0.87, −0.14). The quality of the evidences of daily steps, MVPA and sedentary time was evaluated by very low, very low and low, respectively. Conclusions In this NMA, there's low quality evidence that financial incentive combined with wearable activity tracker is the most effective intervention for increasing daily steps of older adults, wearable activity tracker combined with electronic and mobile health and structured exercise program is the most effective intervention to help older adults to increase MVPA and reduce sedentary time.

Autolysins are endogenous cell wall degrading enzymes (CWDEs) in bacteria that remodel the peptidoglycan layer of its own cell wall. In the Bacillus subtilis genome, at least 35 autolysin genes have been identified. However, the study of their roles in bacterial physiology has been hampered by their complexity and functional redundancy. B. subtilis GLB191 is an effective biocontrol strain against grape downy mildew disease, the biocontrol effect of which results from both direct effect against the pathogen and stimulation of the plant defense. In this study, we show that the autolysin N-acetylglucosaminidase LytD, a major autolysin of vegetative growth in B. subtilis, plays an important role in its biocontrol activity against grape downy mildew. Disruption of lytD resulted in reduced suppression of the pathogen Plasmopara viticola and stimulation of the plant defense. LytD is also shown to affect the biofilm formation and colonization of B. subtilis on grape leaves. This is the first report that demonstrates the role of an endogenous CWDE in suppressing plant disease infection of a biological control microorganism. These findings not only expand our knowledge on the biological function of autolysins but also provide a new target to promote the biocontrol activity of B. subtilis.

With the aging of the population, the quality of life and happiness of the elderly are increasingly becoming concerns of society. Smart senior care (SSC) products are an important tool to improve the quality of life of the elderly, and their application has been widely discussed. However, due to differences in cognitive characteristics and habits of the elderly, they may face difficulties when using smart products. Therefore, how to design a suitable SSC product APP interface for the elderly has become an urgent problem to be solved. The rapid development of deep learning (DL) provides a new way to deal with this problem. This paper aims to optimize the APP interface design of SSC products suitable for the elderly by using DL technology. Specifically, this paper designs a model based on a deep-Q-network (DQN) algorithm, which can better adapt to the usage habits and needs of the elderly through training and optimization. At the same time, the proposed model is evaluated comprehensively to verify its performance and superiority. To achieve the above goals, this paper first summarizes the existing SSC technology and the design suitable for the elderly. On this basis, a model based on the DQN algorithm is designed, and four datasets are used for training and testing. In the design of the model, this paper pays special attention to how to make the interface more friendly and easy to operate to meet the specific demands and preferences of the elderly. After a comprehensive evaluation, it is found that the proposed DQN algorithm model has achieved remarkable improvement in performance. This model has an average return of about 8.8 and 3.9 compared to other models, which have an average return of about 0.9 and 0.2, respectively. This shows that the model designed in this paper performs well in terms of accuracy and average return and performs better than other algorithms. The results of this paper reveal that optimizing the age-appropriate design of the SSC product APP interface through DL technology can notably enhance the user experience and satisfaction of the elderly. This not only helps the elderly to make better use of smart products and improve their quality of life but also provides useful inspiration and guidance for research and practice in related fields.

Buffalo meat is gaining popularity for its nutritional properties, such as its low fat and cholesterol content. However, it is often unsatisfactory to consumers due to its dark color and low tenderness. There is currently limited research on the regulatory mechanisms of buffalo meat quality. Xinglong buffalo are raised in the tropical Hainan region and are undergoing genetic improvement from draught to meat production. For the first time, we evaluated the meat quality traits of Xinglong buffalo using the longissimus dorsi muscle and compared them to Hainan cattle. Furthermore, we utilized a multi-omics approach combining transcriptomics and metabolomics to explore the underlying molecular mechanism regulating meat quality traits. We found that the Xinglong buffalo had significantly higher meat color redness but lower amino acid content and higher shear force compared to Hainan cattle. Differentially expressed genes (DEGs) and differentially accumulated metabolites (DAMs) were identified, with them being significantly enriched in nicotinic acid and nicotinamide metabolic and glycine, serine, and threonine metabolic pathways. The correlation analysis revealed that those genes and metabolites (such as: GAMT, GCSH, PNP, L-aspartic acid, NADP+, and glutathione) are significantly associated with meat color, tenderness, and amino acid content, indicating their potential as candidate genes and biological indicators associated with meat quality. This study contributes to the breed genetic improvement and enhancement of buffalo meat quality.

Age-related sarcopenia places a tremendous burden on healthcare providers and patients' families. Blood flow restriction (BFR) training may be a promising treatment to bring sarcopenia down, and it offers numerous advantages over traditional resistance training. The purpose of this review was to compare the effects of BFR training and conventional resistance training on clinically delayed sarcopenia in the elderly. Databases such as PubMed, Web of Science, Embase, and Science Direct were searched to identify eligible studies; blinded data extraction was performed to assess study quality, and conflicts were submitted to third parties. Someone made the decision. One author used Review Manager (RevMan) 5.4 and compared it with data obtained by another author for this purpose. A total of 14 studies met the inclusion criteria for this review. The funnel plots of the studies did not show any substantial publication bias. Low-load blood flow restriction (LL-BFR) had no significant effect on muscle mass compared with high-load resistance training (HL-RT) (p ​= ​0.74, SMD ​= ​0.07, 95% CI: 0.33 to 0. 46) and LL-BFR had a significant effect on muscle strength compared with HL-RT (p ​= ​0.03, Z ​= ​2.16, SMD ​= ​-0.34, 95% CI: 0.65 to -0.03). LL-BFR showed a slight effect on mass compared to LL-RT (p ​= ​0.26, SMD ​= ​0.25, 95% CI: 0.19 to 0.69). Sensitivity analysis produced a nonsignificant change, suggesting that the results of this study are reasonable. In conclusion, the data suggest the possibility that BFR training improves age-related sarcopenia.

Abstract Siamese networks have attracted wide attention in visual tracking due to their competitive accuracy and speed. However, the existing Siamese trackers usually leverage a fixed linear aggregation of feature maps, which does not effectively fuse the different layers of features with attention. Besides, most of Siamese trackers calculate the similarity between the template and the search region through a cross‐correlation operation between the features of the last blocks from the two branches, which might introduce the redundant noise information. In order to solve these problems, this study proposes a novel Siamese visual tracking method via cross‐layer calibration fusion, termed SiamCCF. An attention‐based feature fusion module is employed using local attention and non‐local attention to fuse the features from the deep and shallow layers, so as to capture both local details and high‐level semantic information. Moreover, a cross‐layer calibration module can use the fused features to calibrate the features of the last network blocks and build the cross‐layer long‐range spatial and inter‐channel dependencies around each spatial location. Extensive experiments demonstrate that the proposed method has achieved competitive tracking performance compared with state‐of‐the‐art trackers on challenging benchmarks, including OTB100, OTB2013, UAV123, UAV20L, and LaSOT.

Abstract This study examined the associations between emerging lipid biomarkers (small dense low‐density lipoprotein cholesterol [sdLDL‐C), lipoprotein(a) [Lp(a)], and free fatty acids [FFA]), two ratios (sdLDL‐C/LDL‐C and the triglyceride–glucose [TyG) index), and the Gensini score (GS) in patients with premature coronary artery disease (PCAD) in relation to the extent of coronary stenosis. The authors evaluated a cohort of 2952 individuals undergoing coronary angiography (CAG), encompassing those with PCAD (n = 1749), late‐onset coronary artery disease (LCAD; n = 328), and non‐coronary artery disease (non‐CAD; n = 575). Noteworthy differences were observed in the levels of the novel lipid biomarkers and ratio indexes among the PCAD, LCAD, and non‐CAD groups (p 40) in PCAD patients, as evidenced by the ROC analysis. In conclusion, sdLDL‐C, Lp(a), FFA, and the sdLDL‐C/LDL‐C and TyG indexes have considerable potential as risk and diagnostic markers for coronary artery stenosis in individuals afflicted with PCAD.

Obesity-induced type 2 diabetes is mainly due to excessive free fatty acids leading to insulin resistance. Increasing thermogenesis is regarded as an effective strategy for hypolipidemia and hypoglycemia. Ginsenoside is a natural active component in Panax ginseng C.A. Meyer, and some of them enhance thermogenesis. However, there are few studies on the mechanism and target of ginsenosides enhancing thermogenesis. Using thermogenic protein uncoupling protein 1 (UCP1)-luciferase reporter assay, we identified ginsenoside F1 as a novel UCP1 activator in the ginsenosides library. Using pull down assay and inhibitor interference, we found F1 binds to β3-adrenergic receptors (β3-AR) to enhance UCP1 expression via cAMP/PKA/CREB pathway. We also investigated the ability of F1 on energy metabolism in obesity-induced diabetic mice, including body weight, body composition and energy expenditure. The results of proteomics showed that F1 significantly up-regulated thermogenesis proteins and lipolytic proteins, but down-regulated fatty acid synthesis proteins. Ginsenoside F1 increased thermogenesis and ameliorated insulin resistance specifically by promoting the browning of white adipose tissue in obese mice. Additionally, ginsenoside F1 improves norepinephrine-induced insulin resistance in adipocytes and hepatocytes, and shows a stronger mitochondria respiration ability than norepinephrine. These findings suggest that ginsenoside F1 is a promising lead compound in the improvement of insulin resistance.

Abstract Psoriasis is a common inflammatory disease of especially high recurrence rate (90%) which is suffered by approximately 3% of the world population. The overexpression of reactive oxygen species (ROS) plays a critical role in psoriasis progress. Here we show that biomimetic iron single-atom catalysts (FeN4O2-SACs) with broad-spectrum ROS scavenging capability can be used for psoriasis treatment and relapse prevention via related gene restoration. FeN4O2-SACs demonstrate attractive multiple enzyme-mimicking activities based on atomically dispersed Fe active structures, which are analogous to those of natural antioxidant enzymes, iron superoxide dismutase, human erythrocyte catalase, and ascorbate peroxidase. Further, in vitro and in vivo experiments show that FeN4O2-SACs can effectively ameliorate psoriasis-like symptoms and prevent the relapse with augmented efficacy compared with the clinical drug calcipotriol. Mechanistically, estrogen receptor 1 (ESR1) is identified as the core protein upregulated in psoriasis treatment through RNA sequencing and bioinformatic analysis. Together, this study provides a proof of concept of psoriasis catalytic therapy (PCT) and multienzyme-inspired bionics (MIB).

Based on the scattering characteristic, the comparison of RCS (radar cross-section) at different positions of a target in the same direction of incidence can be obtained first by extruding or deleting part of the entity. A simulation method of aerial&space targets echo characteristics (A&STEC) is proposed that is universal to aerial and space targets. We utilize a fixed-wing UAV (unmanned aerial vehicle) and typical missiles in simulation. The echo signal modulation characteristic parameters are calculated theoretically by the atmospheric attenuation model, the finite element method and a MUMPS solver. The verification simulations show that this method can analyze the influence of the target shape, incident direction, detection position and detection frequency on echo waveform, intensity and energy distribution. The results show that the profile of echo waveform can invert the general shape of the target. The relationship between time and intensity can determine whether the target is moving towards or away from the detector in addition. These conclusions can provide a reference for the ballistic missile target tracking and the defense against UVA intrusion in theory.

Abstract Background The mitochondrial gene MCCC2, a subunit of the heterodimer of 3-methylcrotonyl-CoA carboxylase, plays a pivotal role in catabolism of leucine and isovaleric acid. The molecular mechanisms and prognostic value still need to be explored in the context of specific cancers, including colorectal cancer (CRC). Methods In vitro and in vivo cell-based assays were performed to explore the role of MCCC2 in CRC cell proliferation, invasion, and migration. Mitochondrial morphology, membrane potential, intracellular reactive oxygen species (ROS), telomerase activity, and telomere length were examined and analyzed accordingly. Protein complex formation was detected by co-immunoprecipitation (CO-IP). Mitochondrial morphology was observed by transmission electron microscopy (TEM). The Cancer Genome Atlas (TCGA) CRC cohort analysis, qRT-PCR, and immunohistochemistry (IHC) were used to examine the MCCC2 expression level. The association between MCCC2 expression and various clinical characteristics was analyzed by chi-square tests. CRC patients’ overall survival (OS) was analyzed by Kaplan–Meier analysis. Results Ectopic overexpression of MCCC2 promoted cell proliferation, invasion, and migration, while MCCC2 knockdown (KD) or knockout (KO) inhibited cell proliferation, invasion, and migration. MCCC2 KD or KO resulted in reduced mitochondria numbers, but did not affect the gross ATP production in the cells. Mitochondrial fusion markers MFN1, MFN2, and OPA1 were all upregulated in MCCC2 KD or KO cells, which is in line with a phenomenon of more prominent mitochondrial fusion. Interestingly, telomere lengths of MCCC2 KD or KO cells were reduced more than control cells. Furthermore, we found that MCCC2 could specifically form a complex with telomere binding protein TRF2, and MCCC2 KD or KO did not affect the expression or activity of telomerase reverse transcriptase (TERT). Finally, MCCC2 expression was heightened in CRC, and patients with higher MCCC2 expression had favorable prognosis. Conclusions Together, we identified MCCC2 as a novel mediator between mitochondria and telomeres, and provided an additional biomarker for CRC stratification.

Abstract Background Despite the availability of a wide range of critical thinking instruments, there was no original design for nurses that has been translated into Chinese. However, only instruments designed specifically for the nursing discipline would be reliable. This study aimed to translate, culturally adapt, and validate the Yoon Critical Thinking Disposition Instrument in the Chinese context. Methods A four-step translation process was implemented according to Word Health Organization guidelines, which included forward translation, expert panel review, backward translation, and pre-testing. Experts and nursing students participated in testing the validity and reliability of the Chinese version. Results The translation of the instrument went smoothly. According to a confirmatory factor analysis, there was an acceptable fit for the seven-factor model. Content validity indices ranged from 0.6 to 1 at item level, and 0.94 at scale level. In addition, there was extremely high internal consistency and test-retest reliability in the translated instrument. There was a good fit for the items with both person and item reliabilities greater than 0.6 and a separation index of 2.19, respectively. The item location was identified from the wright map as not covering person ability, but the scale did not have a gender-related differential item functioning. Conclusions In this study, a critical thinking disposition instrument for nursing students was translated into Chinese for the first time. This translated instrument is a reliable tool with satisfactory validity and reliability. It could provide opportunities for building a cross-cultural understanding of critical thinking disposition.

Abstract Aim The dementia population is expanding fast globally, posing a huge challenge to the healthcare system. Improving the level of Alzheimer's disease knowledge (ADK) in nursing staff is the key to providing quality dementia care and improving the patients' quality of life. This study aimed to investigate and classify the ADK level of nursing staff in East China and to identify the factors influencing the nursing staff's ADK level. Design A cross‐sectional study. Methods A cross‐sectional survey was conducted among 1896 nursing staff in East China from September 2022 to December 2022, using a self‐designed general information questionnaire and the Chinese version of the Alzheimer's Disease Knowledge Scale. Latent profile analysis (LPA) was used to classify the nursing staff according to their ADK level, and multinomial logistic regression was used to identify the factors influencing the nursing staff's ADK level. Results Nursing staff could be classified into four latent profiles according to their ADK level (p

Pre-trained language models (PLMs) are proficient at understanding context in plain text but often struggle with the nuanced linguistics of task-oriented dialogues. The information exchanges in dialogues and the dynamic role-shifting of speakers contribute to complex coreference and interlinking phenomena across multi-turn interactions. To address these challenges, we propose Coreference-Enhanced Contrastive Pre-training (CECPT), an innovative pre-training framework specifically designed to enhance dialogue modeling. CECPT utilizes unsupervised dialogue datasets to capture both semantic richness and structural coherence. Our experimental results demonstrate that the CECPT model significantly outperforms established baselines in three critical applications: intent recognition, dialogue act prediction, and dialogue state tracking. These findings suggest that CECPT is more adept at following the information flow within dialogues and accurately linking statuses to their respective references.

The impacts of the growth and linkage of fault segments on sedimentation in a lacustrine rift basin, the Weixinan Depression, the Beibuwan Basin, in the northern South China Sea, which has been demonstrated to have huge petroleum potential, are elucidated on the basis of well-constrained 3D seismic data. Two main fault systems, the No. 1 boundary fault system and the No. 2 fault system, were developed in the Weixinan Depression. The evolution of the lower basement is based on the No. 1 fault system, which controls the distribution of depocenters (ranging from 450–800 m) within the lower structural layer. It includes the five fault segments isolated at the initial stage, the interaction and propagation stage, the linkage stage, and the decline stage. The No. 2 fault system governs the deposition of the upper structural layer with a series of discrete depocenters in the hangingwall. Initially, it comprises several right-order echelon branching faults. Each branch fault rapidly reached the existing length and maintained a constant length while establishing soft links with each other in the subsequent displacement accrual. The development of topographic slopes, transition zones, transverse anticlines, and related fault troughs and gullies related to the activity of the No. 1 boundary fault system is the main controlling factor that induces the differential development of the western, middle, and eastern sections of steep slope fans. The differential subsidence effect along the No. 2 fault system is responsible for the multiple ‘rising-stable’ stage changes in the relative lake level during the development of axial delta deposits. This study will help elucidate the different controls of extensional fault systems on associated sedimentation, as well as rift basin development in the South China Sea and similar areas throughout the world.

B-box (BBX) proteins, a subfamily of zinc-finger transcription factors, are involved in various environmental signaling pathways. In this study, we conducted a comprehensive analysis of BBX family members in Brassica crops. The 482 BBX proteins were divided into five groups based on gene structure, conserved domains, and phylogenetic analysis. An analysis of nonsynonymous substitutions and (Ka)/synonymous substitutions (Ks) revealed that most BBX genes have undergone purifying selection during evolution. An analysis of transcriptome data from rapeseed (Brassica napus) organs suggested that BnaBBX3d might be involved in the development of floral tissue-specific RNA-seq expression. We identified numerous light-responsive elements in the promoter regions of BnaBBX genes, which were suggestive of participation in light signaling pathways. Transcriptomic analysis under shade treatment revealed 77 BnaBBX genes with significant changes in expression before and after shading treatment. Of these, BnaBBX22e showed distinct expression patterns in yellow- vs. black-seeded materials in response to shading. UPLC-HESI-MS/MS analysis revealed that shading influences the accumulation of 54 metabolites, with light response BnaBBX22f expression correlating with the accumulation of the flavonoid metabolites M46 and M51. Additionally, BnaBBX22e and BnaBBX22f interact with BnaA10.HY5. These results suggest that BnaBBXs might function in light-induced pigment accumulation. Overall, our findings elucidate the characteristics of BBX proteins in six Brassica species and reveal a possible connection between light and seed coat color, laying the foundation for further exploring the roles of BnaBBX genes in seed development.

Mycoplasma capricolum subsp. capricolum (Mcc), a member of the Mycoplasma mycoides cluster, has a negative impact on the goat-breeding industry. However, little is known about the pathogenic mechanism of Mcc. This study infected mice using a previously isolated strain, Mcc HN-B. Hematoxylin and eosin staining, RNA sequencing, bioinformatic analyses, RT-qPCR, and immunohistochemistry were performed on mouse lung tissues. The results showed that 235 differentially expressed genes (DEGs) were identified. GO and KEGG enrichment analyses suggested that the DEGs were mainly associated with immune response, defensive response to bacteria, NF-kappa B signaling pathway, natural killer cell-mediated cytotoxicity, and T cell receptor signaling pathway. RT-qPCR verified the expression of Ccl5, Cd4, Cd28, Il2rb, Lck, Lat, Ptgs2, S100a8, S100a9, and Il-33. The up-regulation of S100A8 and S100A9 at the protein level was confirmed by immunohistochemistry. Moreover, RT-qPCR assays on Mcc HN-B-infected RAW264.7 cells also showed that the expression of S100a8 and S100a9 was elevated. S100A8 and S100A9 not only have diagnostic value in Mcc infection but also hold great significance in clarifying the pathogenic mechanism of Mcc. This study preliminarily elucidates the mechanism of Mcc HN-B-induced lung injury and provides a theoretical basis for further research on Mcc–host interactions.

Groundwater resources is not only important essential water resources but also imperative connectors within the intricate framework of the ecological environment. High nitrate concentrations in groundwater can exerting adverse impacts on human health. It is imperative to accurately delineate the distribution characteristics of groundwater nitrate concentrations. Four different machine learning models (Gradient Boosting Regression (GB), Random Forest Regression (RF), Extreme Gradient Boosting Regression (XG) and Adaptive Boosting Regression (AD)) which combine spatial environmental data and different radius contributing area was developed to predict the distribution of nitrate concentration in groundwater. The models use 595 groundwater samples and included topography, remote sensing, hydrogeological and hydrological, climate, nitrate input, and socio-economic predictor. Gradient Boosting Regression model outperforms the other models (R2 = 0.627, MAE = 0.529, RMSE = 0.705, PICP = 0.924 for test dataset) under 500 m radius contributing area. A high-resolution (1 km) groundwater nitrate concentration distribution map reveal in the majority of the study area, groundwater nitrate concentrations are below 1 mg/L and high nitrate concentration (>10 mg/L) proportion in southeast, northeast and central main urban area karst valley regions is 1.89%, 0.91%, and 0.38% respectively. In study area, hydrogeological conditions, soil parameters, nitrogen input factors, and percentage of arable land are among the most influential explanatory factors. This work, serving as the inaugural application of utilizing effective spatial methods for predicting groundwater nitrate concentrations in Chongqing city, furnish decision-making support for the prevention and control of groundwater pollution, particularly in areas primarily dependent on groundwater for water supply and holds profound significance as a milestone achievement.

Summary: Iron overload is closely associated with metabolic dysfunction. However, the role of iron in the hypothalamus remains unclear. Here, we find that hypothalamic iron levels are increased, particularly in agouti-related peptide (AgRP)-expressing neurons in high-fat-diet-fed mice. Using pharmacological or genetic approaches, we reduce iron overload in AgRP neurons by central deferoxamine administration or transferrin receptor 1 (Tfrc) deletion, ameliorating diet-induced obesity and related metabolic dysfunction. Conversely, Tfrc-mediated iron overload in AgRP neurons leads to overeating and adiposity. Mechanistically, the reduction of iron overload in AgRP neurons inhibits AgRP neuron activity; improves insulin and leptin sensitivity; and inhibits iron-induced oxidative stress, endoplasmic reticulum stress, nuclear factor κB signaling, and suppression of cytokine signaling 3 expression. These results highlight the critical role of hypothalamic iron in obesity development and suggest targets for treating obesity and related metabolic disorders.

Dementia, with homocysteine (Hcy) as an important risk factor, is a severe public health problem in the aging society. Betaine serves as a methyl donor and plays an important role in reducing Hcy. However, the effects and mechanisms of betaine on Hcy-induced cognitive impairment remain unclear. Firstly, SD rats were injected with Hcy (400 μg/kg) through vena caudalis, and betaine (2.5 % w/v) was supplemented via drinking water for 14 days. Betaine supplementation could attenuate Hcy-induced cognitive impairment in the Y maze and novel object recognition tests by repairing brain injury. Meanwhile, microglial activation was observed to be inhibited by betaine supplementation using immunofluorescence and sholl analysis. Secondly, HMC3 cells were treated with betaine, which was found to decrease the ROS level, ameliorate cell membrane rupture, reduce the release of LDH, IL-18 and IL-1β, and attenuate the damage of microglia to neurons. Mechanistically, betaine alleviates cognitive impairment by inhibiting microglial pyroptosis via reducing the expressions of NLRP3, ASC, pro-caspase-1, cleaved-caspase-1, GSDMD, GSDMD-N, IL-18 and IL-1β. Betaine treatment can increase SAM/SAH ratio, confirming its enhancement on methylation capacity. Furthermore, betaine treatment was found to enhance N6-methyladenosine (m6A) modification of NLRP3 mRNA, and reduced the NLRP3 mRNA stability through increasing the expression of the m6A reader YTH N6-methyladenosine RNA binding protein 2 (YTHDF2). Finally, silencing YTHDF2 could reverse the inhibitory effect of betaine on pyroptosis. Our data demonstrated that betaine attenuated Hcy-induced cognitive impairment by suppressing microglia pyroptosis via inhibiting the NLRP3/caspase-1/GSDMD pathway in an m6A-YTHDF2-dependent manner.

Macroalgae cultivation is receiving growing attention as a potential carbon dioxide removal (CDR) strategy. Macroalgae biomass harvesting and/or intentional sinking have been the main focus of research efforts. A significant amount of biomass is naturally lost through erosion and breakage of cultivated or naturally growing seaweed, but the contribution of the resulting particulates to carbon sequestration is relatively unexplored. Here, we use a fully coupled kelp-biogeochemistry model forced by idealized parameters in a closed system to estimate the potential of macroalgal-derived particulate organic carbon (POC) sinking as a CDR pathway. Our model indicates that at a kelp density of 1.1 fronds m−3, macroalgal POC sinking can export 7.4 times more carbon to the deep sea (depths > 500m) and remove 5.2 times more carbon from the atmosphere (equivalent to an additional 336.0 gC m−2 yr−1) compared to the natural biological pump without kelp in our idealized closed system. The results suggest that CDR associated with POC sinking should be explored as a possible benefit of seaweed farming and point to the need for further study on organic carbon partitioning and its bioavailability to quantify the effectiveness and impacts of macroalgal cultivation as a CDR strategy.

Ferroptosis is a novel cell death mechanism that is mediated by iron-dependent lipid peroxidation. It may be involved in atherosclerosis development. Products of phospholipid oxidation play a key role in atherosclerosis. 1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphocholine (PGPC) is a phospholipid oxidation product present in atherosclerotic lesions. It remains unclear whether PGPC causes atherosclerosis by inducing endothelial cell ferroptosis. In this study, human umbilical vein endothelial cells (HUVECs) were treated with PGPC. Intracellular levels of ferrous iron, lipid peroxidation, superoxide anions (O2•−), and glutathione were detected, and expression of fatty acid binding protein-3 (FABP3), glutathione peroxidase 4 (GPX4), and CD36 were measured. Additionally, the mitochondrial membrane potential (MMP) was determined. Aortas from C57BL6 mice were isolated for vasodilation testing. Results showed that PGPC increased ferrous iron levels, the production of lipid peroxidation and O2•−, and FABP3 expression. However, PGPC inhibited the expression of GPX4 and glutathione production and destroyed normal MMP. These effects were also blocked by ferrostatin-1, an inhibitor of ferroptosis. FABP3 silencing significantly reversed the effect of PGPC. Furthermore, PGPC stimulated CD36 expression. Conversely, CD36 silencing reversed the effects of PGPC, including PGPC-induced FABP3 expression. Importantly, E06, a direct inhibitor of the oxidized 1-palmitoyl-2-arachidonoyl-phosphatidylcholine IgM natural antibody, inhibited the effects of PGPC. Finally, PGPC impaired endothelium-dependent vasodilation, ferrostatin-1 or FABP3 inhibitors inhibited this impairment. Our data demonstrate that PGPC impairs endothelial function by inducing endothelial cell ferroptosis through the CD36 receptor to increase FABP3 expression. Our findings provide new insights into the mechanisms of atherosclerosis and a therapeutic target for atherosclerosis.

In this paper, we study the micro-motion characteristics of multi-feature targets based on a double pulse coherent system under atmospheric conditions. The theoretical model for echo signal and micro-motion characteristics of a 3D target in double pulse coherent system is deduced. We discuss the influence of micro-motion characteristics, the relative size of light spot and target, target shapes, and incident direction on frequency shift. LRCS (Lidar cross-section), echo waveform, intensity and radiation energy distribution under different conditions are obtained additionally. Simulation results conclude that these parameters are of advantage to the inversion of target shape properties and motion types.

Background: With societal and economic development, the annual incidence of chronic kidney disease (CKD) is increasing. Current treatments for CKD are limited, and once patients progress to the uraemic stage, it places a significant economic burden on families and society. Based on the “gut–kidney axis” theory and real-world research, this study aims to evaluate the clinical efficacy, safety, and potential mechanism of high-position colon dialysis combined with traditional Chinese medicine (TCM) retention enema in treating stage 3–5 chronic kidney disease (non-dialysis). Additionally, it seeks to identify new therapeutic targets and approaches for CKD treatment.Methods: The TCM decoction was analyzed using Ultra-Performance Liquid Chromatography-Quadrupole-Orbitrap-High Resolution Mass Spectrometry (UPLC-Q-Orbitrap-HRMS). Participants meeting the inclusion criteria were divided into a control group (n = 153) and a treatment group (n = 159) based on their preferences and physicians’ recommendations. Both groups adhered to a high-quality low-protein, low-salt, low-phosphorus, and low-fat diet supplemented with essential amino acids, and were monitored for blood pressure, blood glucose, and blood lipids. The treatment group received high-position colon dialysis combined with TCM retention enemas (administered at least 12 times every other day).Results: Thirteen compounds were identified from the herbs by UPLC-Q-Orbitrap-HRMS. The CKD3–5 treatment group exhibited improvements in blood biochemistry and other laboratory indices, with significant enhancements in renal function-related indices for CKD4 and CKD5 stages (p < 0.05). Following treatment, indoxyl sulfate (IS), endotoxin, and D-lactic acid levels decreased to a certain extent in both groups, with a statistically significant difference observed within the treatment group (p < 0.05). The treatment group displayed a significant reduction in aerobic bacterial colonies, an increase in anaerobic bacterial colonies, a decrease in Escherichia coli colonies, and an increase in Bifidobacterium and Lactobacillus colonies (p < 0.05). No significant changes in colony numbers were observed in the control group.Conclusion: High-position colon dialysis combined with TCM retention enema may serve as an adjuvant treatment for CKD4-5 (non-dialysis), and its mechanism may be related to the reduction of uraemic toxins, improvement of intestinal mucosal barrier function, and regulation of intestinal microecology.Clinical Trial Registration:https://www.chictr.org.cn/, identifier ChiCTR2200062852.

The prevalence of infectious diseases in sheep and goats has a significant impact on the development of the sheep and goat industry and public health security. The identification and analysis of pathogens are crucial for infectious disease research; however, existing databases pay little attention to sheep and goat diseases, and pathogen data are relatively scattered. Therefore, the effective integration, analysis and visualization of these data will help us conduct in-depth research on sheep and goat infectious diseases and promote the formulation of disease prevention and control strategies. This article considered the pathogens of 44 infectious diseases in sheep and goats as the main research objects and collected and downloaded relevant scientific literature, pathogen genomes, pathogen transcriptomes, pathogen occurrence records, and other data. The C# programming language and an SQL Server database were used to construct and realize the functions of the Sheep and Goat Pathogen Database (SGPD) within a B/S architecture based on the ASP.NET platform. The SGPD mainly provides an integrated platform for sheep and goat pathogen data retrieval, auxiliary analysis, and user upload, including several functionalities: (1) a Disease Introduction module that queries basic information regarding the 44 recorded sheep and goat infectious diseases, such as epidemiology, clinical characteristics, diagnostic criteria, and prevention and control measures; (2) an Omics Information module that allows users to query and download the genome and transcriptome data related to the pathogens of sheep and goat infectious disease, and provide sequence alignment functionality; (3) a Pathogen Structure module that enables users to view electron micrographs of pathogen structure and tissue sections related to sheep and goat disease from publicly published research; (4) a Literature Search module based on the “Pathogen Dictionary” search strategy that facilitates searches for published research related to pathogens of infectious disease; (5) a Science Popularization module that allows users to view popular science materials related to sheep and goat infectious diseases; and (6) a Public Health module that allows users to query the risk factors of zoonotic disease transmission and the corresponding related literature, and realize the visualization of pathogen distribution. The SGPD is a specialized sheep and goat pathogen information database that provides comprehensive resources and technical support for sheep and goat infectious disease research, prevention, and control.

Meeting the goal of zero emissions in the energy sector by 2050 requires accurate prediction of energy consumption, which is increasingly important. However, conventional bottom-up model-based heat demand forecasting methods are not suitable for large-scale, high-resolution, and fast forecasting due to their complexity and the difficulty in obtaining model parameters. This paper presents an artificial neural network (ANN) model to predict hourly heat demand on a national level, which replaces the traditional bottom-up model based on extensive building simulations and computation. The ANN model significantly reduces prediction time and complexity by reducing the number of model input types through feature selection, making the model more realistic by removing non-essential inputs. The improved model can be trained using fewer meteorological data types and insufficient data, while accurately forecasting the hourly heat demand throughout the year within an acceptable error range. The model provides a framework to obtain accurate heat demand predictions for large-scale areas, which can be used as a reference for stakeholders, especially policymakers, to make informed decisions.

Light is an underappreciated mood manipulator. People are often exposed to electronic equipment, which results in nocturnal blue light exposure in modern society. Light pollution drastically shortens the night phase of the circadian rhythm. Preclinical and clinical studies have reported that nocturnal light exposure can influence mood, such as depressive-like phenotypes. However, the effects of blue light at night (BLAN) on other moods and how it alters mood remain unclear. Here, we explored the impact of BLAN on stress-provoked aggression in male Sprague‒Dawley rats, focusing on its influence on basolateral amygdala (BLA) activity. Resident-intruder tests, extracellular electrophysiological recordings, and enzyme-linked immunosorbent assays were performed. The results indicated that BLAN produces stress-induced heightened aggressive and anxiety-like phenotypes. Moreover, BLAN not only potentiates long-term potentiation and long-term depression in the BLA but also results in stress-induced elevation of brain-derived neurotrophic factor (BDNF), mature BDNF, and phosphorylation of tyrosine receptor kinase B expression in the BLA. Intra-BLA microinfusion of BDNF RNAi, BDNF neutralizing antibody, K252a, and rapamycin blocked stress-induced heightened aggressive behavior in BLAN rats. In addition, intra-BLA application of BDNF and 7,8-DHF caused stress-induced heightened aggressive behavior in naïve rats. Collectively, these results suggest that BLAN results in stress-evoked heightened aggressive phenotypes, which may work by enhancing BLA BDNF signaling and synaptic plasticity. This study reveals that nocturnal blue light exposure may have an impact on stress-provoked aggression. Moreover, this study provides novel insights into the BLA BDNF-dependent mechanism underlying the impact of the BLAN on mood.

Exercise-induced muscle damage (EIMD) is a common phenomenon resulting from high intensity exercise that impairs subsequent performance. Ischaemic post-conditioning (IPOC) is a simple intervention that has been shown to reduce muscle damage after prolonged ischaemia, a condition mechanistically similar to EIMD. The purpose of this study was to determine whether IPOC could alleviate muscle damage after eccentric exercise. Thirty-two young male participants were randomized into either a sham ( n = 16) or an IPOC ( n = 16) intervention group. Biceps brachii muscle damage was induced by eccentric exercise, with IPOC or sham intervention applied on the dominant arm following exercise (3 cycles of 30 s ischaemia). Visual analogue scale (VAS) pain, arm circumference, muscle thickness, echo intensity, and microvascular function (using near-infrared spectroscopy) were measured bilaterally at baseline, 24, 48, and 72 hours after eccentric exercise. Biceps curl one repetition maximum (1RM) was also measured. 1RM was higher for the IPOC group at 48 and 72 hours (both p < 0.05). On the dominant arm, VAS pain was lower at 72 hours for the IPOC group ( p = 0.039). Muscle thickness was lower at all post-exercise time points for the IPOC group (all p < 0.05). VAS pain, echo-intensity, and arm circumference were elevated on the non-dominant arm in the sham group at 72 hours (all p < 0.05). These parameters all returned to the baseline level for the IPOC group at 72 hours (all p > 0.05IPOC could attenuate the decrease in strength, and alleviate EIMD with both local and remote effects after high-intensity exercise.

Abstract Disentangling the assembly mechanisms controlling community composition, structure, distribution, functions, and dynamics is a central issue in ecology. Although various approaches have been proposed to examine community assembly mechanisms, quantitative characterization is challenging, particularly in microbial ecology. Here, we present a novel approach for quantitatively delineating community assembly mechanisms by combining the consumer–resource model with a neutral model in stochastic differential equations. Using time‐series data from anaerobic bioreactors that target microbial 16S rRNA genes, we tested the applicability of three ecological models: the consumer–resource model, the neutral model, and the combined model. Our results revealed that model performances varied substantially as a function of population abundance and/or process conditions. The combined model performed best for abundant taxa in the treatment bioreactors where process conditions were manipulated. In contrast, the neutral model showed the best performance for rare taxa. Our analysis further indicated that immigration rates decreased with taxa abundance and competitions between taxa were strongly correlated with phylogeny, but within a certain phylogenetic distance only. The determinism underlying taxa and community dynamics were quantitatively assessed, showing greater determinism in the treatment bioreactors that aligned with the subsequent abnormal system functioning. Given its mechanistic basis, the framework developed here is expected to be potentially applicable beyond microbial ecology.

Abstract Background Liposarcoma is a malignant mesenchymal tumor that most commonly involves the retroperitoneum and lower extremities. However, liposarcoma of esophagus has been rarely reported in the literature. Case presentation We report a case of a 46-year-old man with complaint of intermittent dysphagia for 6 years, accompanied with paroxysmal vomiting of pedicled tumor to the mouth. Imaging studies showed a huge mixed density lesion in the middle esophageal lumen. Surgical resection of the tumor was performed through an external cervical approach. Microscopically, the tumor was composed of mature adipocytes in normal adipose tissue prominently intersected by sparsely cellular fibrous septa containing atypical, enlarged spindle cells with hyperchromatic nuclei. Immunohistochemically, the tumor cells were positive for Vimentin, S-100, CD34 and MDM2. Besides, fluorescence in situ hybridization (FISH) analysis indicated the presence of amplification involving MDM2 gene. The patient was diagnosed as having esophageal well-differentiated liposarcoma and recovered well after the operation. Conclusions Esophageal liposarcoma is an extremely rare tumor. Due to the nonspecific clinical manifestation and lack of experience, it is challenging to make a clear diagnosis before operation. Definite diagnosis of esophageal liposarcoma depends on histopathology, immunohistochemistry and molecular analysis.

Abstract Background Previous preliminary work found that Latroeggtoxin-VI (LETX-VI), a proteinaceous neurotoxin from the eggs of spider Latrodectus tredecimguttatus, could promote the synthesis and release of dopamine in PC12 cells. However, the underlying mechanisms have not been fully clear. Here, the effects of LETX-VI on the gene expression profile and dopamine in PC12 cells were analyzed with the differential transcriptome-based strategies. Results After treatment of PC12 cells with LETX-VI for 24 h, a total of 356 differentially expressed transcripts were identified. Of them 165 were up-regulated and 191 down-regulated. Relevant GO analysis indicated that LETX-VI modulated the expression of certain genes and thereby affected multiple biological processes in PC12 cells, including protein metabolism, nucleic acid metabolism, substance transport, signaling, neurotransmitter metabolism and release. When western blot analysis was employed to confirm the abundance levels of synaptojanin 1 and synuclein alpha interacting protein, the representatives of highly up- and down-regulated transcript-encoded proteins that are closely related with dopamine respectively, it was found that the level of synaptojanin 1 in the PC12 cells treated with LETX-VI was increased, whereas that of synuclein alpha interacting protein was not obviously altered, suggesting that synaptojanin 1 may be much more involved in the effects of LETX-VI on dopamine. After synaptojanin 1 level was knocked down using siRNA, the levels of both total and released dopamine were significantly decreased, indicating that synaptojanin 1 is a protein positively modulating the synthesis and secretion of dopamine. When the PC12 cells with knocked down synaptojanin 1 were treated by LETX-VI, the adverse effects of synaptojanin 1 knockdown on dopamine were attenuated, confirming that LETX-VI promotes the synthesis and secretion of dopamine at least partially by enhancing the expression of the gene SYNJ1 encoding synaptojanin 1. Conclusions This work demonstrates that LETX-VI exerts multiple regulatory effects on the cellular processes in PC12 cells by altering the gene expression profile. LETX-VI modulates the expression of the genes closely related to the synthesis, transport and release of neurotransmitters especially dopamine in PC12 cells, with the gene SYNJ1 encoding synaptojanin 1 as a main target.

Stapled peptides with significantly enhanced pharmacological profiles have emerged as promising therapeutic molecules due to their remarkable resistance to proteolysis and performance to penetrate cells. The all-hydrocarbon peptide stapling technique has already widely adopted with great success, yielding numerous potent peptide-based molecules. Based on our prior efforts, we conceived and prepared a double-stapled peptide in this study, termed FRNC-1, which effectively attenuated the bone resorption capacity of mature osteoclasts in vitro through specific inhibition of phosphorylated GSK-3β. The double-stapled peptide FRNC-1 displayed notably improved helical contents and resistance to proteolysis than its linear form. Additionally, FRNC-1 effectively prevented osteoclast activation and improved bone density for ovariectomized (OVX) mice after intravenous injection and importantly, after oral (intragastric) administration. The double-stapled peptide FRNC-1 is the first orally effective peptide that has been validated to date as a therapeutic candidate for postmenopausal osteoporosis (PMOP).

Scope: Circadian disorder and high-fat diet (HFD) can disturb lipid metabolism homeostasis and may promote the development of various metabolic diseases. The relationship between them is of great concern. This study aimed to explore the effects of Per1/Per2 double knockout (DKO) on hepatic lipid metabolism in mice under HFD and HFD with docosahexaenoic acid (DHA) substitution. Methods and results: Both wild type (WT) and DKO male C57BL/6 mice were fed with normal chow diet (CON), HFD, or HFD with DHA substitution (AO) for 15 weeks. At the end of the experiment, mice were sacrificed at zeitgeber time (ZT) 0 (7:00 am) or ZT12 (7:00 pm). Pathological indicators were determined using histological and biochemical methods. Hepatic transcriptome sequencing analysis showed that DKO mice exhibited multiple dysfunctions in diurnal rhythm, drug metabolism, cell cycle, cancer pathways, and lipid metabolism. HFD had greater effects on fatty acid oxidation and cholesterol synthesis and metabolism in Per1-/-Per2-/- mice, which was improved by DHA substitution. Conclusions: Per1/Per2 played an important role in the circadian regulation of hepatic lipid metabolism, and DKO mice were more sensitive to HFD. DHA can improve circadian-related lipid metabolism disruption induced by HFD in mice.