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Abstract Fundus fluorescein angiography (FFA) is a crucial diagnostic tool for chorioretinal diseases, but its interpretation requires significant expertise and time. Prior studies have used Artificial Intelligence (AI)-based systems to assist FFA interpretation, but these systems lack user interaction and comprehensive evaluation by ophthalmologists. Here, we used large language models (LLMs) to develop an automated interpretation pipeline for both report generation and medical question-answering (QA) for FFA images. The pipeline comprises two parts: an image-text alignment module (Bootstrapping Language-Image Pre-training) for report generation and an LLM (Llama 2) for interactive QA. The model was developed using 654,343 FFA images with 9392 reports. It was evaluated both automatically, using language-based and classification-based metrics, and manually by three experienced ophthalmologists. The automatic evaluation of the generated reports demonstrated that the system can generate coherent and comprehensible free-text reports, achieving a BERTScore of 0.70 and F1 scores ranging from 0.64 to 0.82 for detecting top-5 retinal conditions. The manual evaluation revealed acceptable accuracy (68.3%, Kappa 0.746) and completeness (62.3%, Kappa 0.739) of the generated reports. The generated free-form answers were evaluated manually, with the majority meeting the ophthalmologists’ criteria (error-free: 70.7%, complete: 84.0%, harmless: 93.7%, satisfied: 65.3%, Kappa: 0.762–0.834). This study introduces an innovative framework that combines multi-modal transformers and LLMs, enhancing ophthalmic image interpretation, and facilitating interactive communications during medical consultation.

Abstract Strategies to improve T cell therapy efficacy in solid tumors such as hepatocellular carcinoma (HCC) are urgently needed. The common cytokine receptor γ chain (γc) family cytokines such as IL-2, IL-7, IL-15 and IL-21 play fundamental roles in T cell development, differentiation and effector phases. This study aims to determine the combination effects of IL-21 in T cell therapy against HCC and investigate optimized strategies to utilize the effect of IL-21 signal in T cell therapy. The antitumor function of AFP-specific T cell receptor-engineered T cells (TCR-T) was augmented by exogenous IL-21 in vitro and in vivo. IL-21 enhanced proliferation capacity, promoted memory differentiation, downregulated PD-1 expression and alleviated apoptosis in TCR-T after activation. A novel engineered IL-21 receptor was established, and TCR-T armed with the novel engineered IL-21 receptors (IL-21R-TCR-T) showed upregulated phosphorylated STAT3 expression without exogenous IL-21 ligand. IL-21R-TCR-T showed better proliferation upon activation and superior antitumor function in vitro and in vivo. IL-21R-TCR-T exhibited a less differentiated, exhausted and apoptotic phenotype than conventional TCR-T upon repetitive tumor antigen stimulation. The novel IL-21 receptor in our study programs powerful TCR-T and can avoid side effects induced by IL-21 systemic utilization. The novel IL-21 receptor creates new opportunities for next-generation TCR-T against HCC.

BackgroundConventional daytime monitoring in a single day may be influenced by factors such as motion artifacts and emotions, and continuous monitoring of nighttime heart rate variability (HRV) and respiration to assist in chronic obstructive pulmonary disease (COPD) diagnosis has not been reported yet. ObjectiveThe aim of this study was to explore and compare the effects of continuously monitored HRV, heart rate (HR), and respiration during night sleep on the remote diagnosis of COPD. MethodsWe recruited patients with different severities of COPD and healthy controls between January 2021 and November 2022. Vital signs such as HRV, HR, and respiration were recorded using noncontact bed sensors from 10 PM to 8 AM of the following day, and the recordings of each patient lasted for at least 30 days. We obtained statistical means of HRV, HR, and respiration over time periods of 7, 14, and 30 days by continuous monitoring. Additionally, the effects that the statistical means of HRV, HR, and respiration had on COPD diagnosis were evaluated at different times of recordings. ResultsIn this study, 146 individuals were enrolled: 37 patients with COPD in the case group and 109 participants in the control group. The median number of continuous night-sleep monitoring days per person was 56.5 (IQR 32.0-113.0) days. Using the features regarding the statistical means of HRV, HR, and respiration over 1, 7, 14, and 30 days, binary logistic regression classification of COPD yielded an accuracy, Youden index, and area under the receiver operating characteristic curve of 0.958, 0.904, and 0.989, respectively. The classification performance for COPD diagnosis was directionally proportional to the monitoring duration of vital signs at night. The importance of the features for diagnosis was determined by the statistical means of respiration, HRV, and HR, which followed the order of respiration > HRV > HR. Specifically, the statistical means of the duration of respiration rate faster than 21 times/min (RRF), high frequency band power of 0.15-0.40 Hz (HF), and respiration rate (RR) were identified as the top 3 most significant features for classification, corresponding to cutoff values of 0.1 minute, 1316.3 nU, and 16.3 times/min, respectively. ConclusionsContinuous monitoring of nocturnal vital signs has significant potential for the remote diagnosis of COPD. As the duration of night-sleep monitoring increased from 1 to 30 days, the statistical means of HRV, HR, and respiration showed a better reflection of an individual's health condition compared to monitoring the vital signs in a single day or night, and better was the classification performance for COPD diagnosis. Further, the statistical means of RRF, HF, and RR are crucial features for diagnosing COPD, demonstrating the importance of monitoring HRV and respiration during night sleep.

Abstract Radionuclides internal radiotherapy (RIT) is a clinically powerful method for cancer treatment, but still poses unsatisfactory therapeutic outcomes due to the hypoxic characteristic of tumor microenvironment (TME). Catalase (CAT) or CAT-like nanomaterials can be used to enzymatically decompose TME endogenous H2O2 to boost TME oxygenation and thus alleviate the hypoxic level within tumors, but their effectiveness is still hindered by the short-lasting of hypoxia relief owing to their poor stability or degradability, thereby failing to match the long therapeutic duration of RIT. Herein, we proposed an innovative strategy of using facet-dependent CAT-like Pd-based two-dimensional (2D) nanoplatforms to continuously enhance RIT. Specifically, rationally designed 2D Pd@Au nanosheets (NSs) enable consistent enzymatic conversion of endogenous H2O2 into O2 to overcome hypoxia-induced RIT resistance. Furthermore, partially coated Au layer afford NIR-II responsiveness and moderate photothermal treatment that augmenting their enzymatic functionality. This approach with dual-effect paves the way for reshaping TME and consequently facilitating the brachytherapy ablation of cancer. Our work offers a significant advancement in the integration of catalytic nanomedicine and nuclear medicine, with the overarching goal of amplifying the clinical benefits of RIT-treated patients. Graphical abstract

BackgroundType 1 diabetes mellitus (T1DM) is frequently associated with various infections, including mycoses; however, the direct link between T1DM and fungal infections remains under-researched. This study utilizes a Mendelian randomization (MR) approach to investigate the potential causal relationship between T1DM and mycoses.MethodsGenetic variants associated with T1DM were sourced from the European Bioinformatics Institute database, while those related to fungal infections such as candidiasis, pneumocystosis, and aspergillosis were obtained from the Finngen database, focusing on European populations. The primary analysis was conducted using the inverse variance weighted (IVW) method, with additional insight from Mendelian randomization Egger regression (MR-Egger). Extensive sensitivity analyses assessed the robustness, diversity, and potential horizontal pleiotropy of our findings. Multivariable Mendelian randomization (MVMR) was employed to adjust for confounders, using both MVMR-IVW and MVMR-Egger to evaluate heterogeneity and pleiotropy.ResultsGenetically, the odds of developing candidiasis increased by 5% in individuals with T1DM, as determined by the IVW method (OR = 1.05; 95% CI 1.02–1.07, p = 0.0001), with a Bonferroni-adjusted p-value of 0.008. Sensitivity analyses indicated no significant issues with heterogeneity or pleiotropy. Adjustments for confounders such as body mass index, glycated hemoglobin levels, and white blood cell counts further supported these findings (OR = 1.08; 95% CI:1.03–1.13, p = 0.0006). Additional adjustments for immune cell counts, including CD4 and CD8 T cells and natural killer cells, also demonstrated significant results (OR = 1.04; 95% CI: 1.02–1.06, p = 0.0002). No causal associations were found between T1DM and other fungal infections like aspergillosis or pneumocystosis.ConclusionThis MR study suggests a genetic predisposition for increased susceptibility to candidiasis in individuals with T1DM. However, no causal links were established between T1DM and other mycoses, including aspergillosis and pneumocystosis.

To external validate the risk assessment model (RAM) of venous thromboembolism (VTE) in multicenter internal medicine inpatients. We prospectively collected 595 internal medical patients (310 with VTE patients, 285 non-VTE patients) were from Beijing Shijitan Hospital, Beijing Chaoyang Hospital, and the respiratory department of Beijing Tsinghua Changgeng Hospital from January 2022 to December 2022 for multicenter external validation. The prediction ability of Caprini RAM, Padua RAM, The International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) RAM, and Shijitan (SJT) RAM were compared. This study included a total of 595 internal medicine inpatients, including 242 (40.67%) in the respiratory department, 17 (2.86%) in the respiratory intensive care unit, 49 (8.24%) in the neurology department, 34 (5.71%) in the intensive care unit, 26 (4.37%) in the geriatric department, 22 (3.70%) in the emergency department, 71 (11.93%) in the nephrology department, 63 (10.59%) in the cardiology department, 24 (4.03%) in the hematology department, 6 (1.01%) in the traditional Chinese medicine department, 9 (1.51%) cases in the rheumatology department, 7 (1.18%) in the endocrinology department, 14 (2.35%) in the oncology department, and 11 (1.85%) in the gastroenterology department. Multivariate logistic regression analysis showed that among internal medicine inpatients, age > 60 years old, heart failure, nephrotic syndrome, tumors, history of VTE, and elevated D-dimer were significantly correlated with the occurrence of VTE ( P .05). The SJT RAM derived from general hospitalized Chinese patients has effective and better predictive ability for internal medicine inpatients at risk of VTE.

Purpose: To explore the association between the cause of amblyopia and pre-treatment contrast sensitivity, stereoacuity, fixation and nystagmus. Design: Retrospective cohort study. Methods: A retrospective review was conducted for 3408 patients with amblyopia who had not yet started amblyopia treatment utilizing a large amblyopia patient database maintained at Zhongshan Ophthalmic Centre. Six amblyogenic factor subtypes were identified: anisometropia, isoametropia, strabismus, anisometropia and strabismus, monocular visual deprivation, and binocular visual deprivation amblyopia. Monocular best corrected visual acuity (BCVA), the contrast sensitivity function (CSF), fixation, and stereopsis were compared between the subtypes before and after propensity score matching (PSM) for age and sex. Results: The two deprivation groups had poorer BCVA and CSF than the other groups. There were no systematic differences in CSF between the non-deprivation groups. Nystagmus was more common in the bilateral amblyopia groups compared to the monocular amblyopia groups. Eccentric fixation was uncommon with the exception of the anisometropia and strabismus group which had an eccentric fixation rate of 20%. Distance stereoacuity measured without monocular cues was absent for almost all patients. The results were consistent when analyzed using PSM. Conclusion: Visual deprivation causes more severe amblyopia than other amblyogenic factors. For non-deprivation amblyopia subtypes, individual differences such as variation in the severity of the amblyogenic factor might be more important in determining pre-treatment vision than whether amblyopia was caused by refractive error, strabismus or both.

Anhydrous hydrogen fluoride (AHF), a critical raw material for industries such as aluminum, pharmaceuticals, and petroleum, has traditionally been sourced from fluorite—a non-renewable mineral. The unsustainable reliance on fluorite has catalyzed the search for alternative AHF production methods. A promising substitute is fluorosilicic acid (FSA), a byproduct of the phosphate fertilizer industry previously deemed waste. Transforming fluorosilicic acid into AHF not only yields a valuable resource but also addresses the environmental and economic challenges associated with waste management. The innovative practice of producing AHF from fluorosilicic acid signals a shift towards sustainable chemical production by capitalizing on waste, potentially diminishing reliance on fluorite and reducing the industry’s environmental impact. This review thoroughly dissects the AHF synthesis process from fluorosilicic acid. Despite the acknowledged importance of fluorinated compounds in numerous industrial applications, research on their synthesis from fluorosilicic acid is limited and fragmented. This review seeks to amalgamate this scattered information by closely scrutinizing diverse industrial processing methods. Additionally, it explores the current and future landscape, economic feasibility, and strategies to navigate the obstacles inherent in synthesizing AHF from fluorosilicic acid. It also assesses the environmental impact of these methods, thereby contributing to the dialogue in this emerging field. The primary aim of this manuscript is to foster further research and promote the industrial uptake of this sustainable process. Highlighting the challenges and proposing potential improvements, the review supports the responsible reuse of waste and advocates for advancements in industrial practices.

Localization is a key technology in wireless sensor network (WSN) applications. The use of mobile anchor nodes (MANs) to assist in sensor localization is a feasible solution for reducing deployment costs and overcoming geographical limitations. However, real-world environments often contain obstacles with signal-blocking characteristics. Random collision methods cannot guarantee that sensors receive sufficient localization information, resulting in the generation of many redundant beacon points by MANs. To achieve complete localization coverage and improve localization accuracy, we propose a path planning and optimization algorithm called M-ANCHORO. The proposed algorithm divides subregions based on obstacle distribution information and deploys beacon points in equilateral triangles. It then uses the SCAN method to plan a fully localized coverage path and optimizes the number of beacon points using a path simplification procedure to establish a trajectory for full localization coverage. Experimental results showed that M-ANCHORO outperformed Z-curve, SLMAT, and SCAN in terms of localization accuracy and coverage.

Collaborative efforts to reduce pollution and carbon emissions are a notable feature of the current era. Achieving the “pollution reduction” and “carbon reduction” dual-driven new development model is the inevitable requirement and significant practical measure for building a new development pattern and realizing a comprehensive green transformation of economic and social development. The synergistic effects between pollution reduction and carbon reduction (PRCR) have been demonstrated. However, the measurement and quantitative analysis of the coupling coordination degree (CCD) of PRCR have not received enough attention. Therefore, the evaluation index system was constructed based on the scientific connotation of PRCR, and the CCD of PRCR in cities along the Yellow River Basin (YRB) from 2009 to 2018 was measured quantitatively by constructing the coupling coordination model in this paper. In addition, we comprehensively investigated its spatial pattern, distribution characteristics, and evolution trend using ESDA, Kernel density estimation, and Markov chain. The primary findings can be summarized as: (1) PRCR levels and their CCD fluctuated and increased in the YRB, with “east-high and west-low” spatial differentiation characteristics, and the coupling phenomenon of “pollution reduction is hindered and carbon reduction is lagging”. (2) There is a phenomenon of “spatial club” clustering in the coordination degree of PRCR in the YRB, with most cities in the downstream areas belonging to the type of high-high clustering, while the middle and upstream areas had the opposite type. (3) The CCD of PRCR in the whole and upper reaches of the YRB have transformed from low-level divergence to high-level convergence. (4) Spatial geographic factors have a significant spillover effect on the evolution of the CCD of PRCR, and there is a phenomenon of the “Matthew effect”. This paper provides a comprehensive framework for analyzing the synergistic effects between PRCR, and the research findings can also provide insights for other regions.

Abstract Kidney fibrosis is the common final pathway of chronic kidney disease (CKD), and it is distinguished by inflammation, mesenchymal transition with myofibroblast formation, and epithelial‐to‐mesenchymal transition (EMT). Macrophages are protuberant inflammatory cells in the kidney, and their roles are dependent on their phenotypes. However, it remains unclear whether tubular epithelial cells (TECs) undergoing EMT can influence the phenotypes of macrophages and the underlying mechanisms during the development of kidney fibrosis. Here, we investigated the characteristics of TECs and macrophages during kidney fibrosis with a focus on EMT and inflammation. We found that the coculture of exosomes from transforming growth factor‐beta (TGF‐β)‐induced TECs with macrophages induced macrophage M1 polarization, while exosomes from TECs without TGF‐β stimulation or stimulation with TGF‐β alone did not induce an increase in M1 macrophage‐related markers. Notably, TECs induced to undergo EMT by TGF‐β treatment released more exosomes than the other groups. Furthermore, it is noteworthy that when we injected exosomes from TECs undergoing EMT into mice, in addition to the high level of inflammatory response and the activation of M1 macrophages, the indicators of EMT and renal fibrosis in mouse kidney tissue were correspondingly elevated. In summary, exosomes from TECs undergoing EMT by TGF‐β treatment induced M1 polarization and led to a positive feedback effect for further EMT and the development of renal fibrosis. Therefore, the obstacle to the release of such exosomes may be a novel therapeutic strategy for CKD.

COVID-19’s global spread had numerous negative consequences for the industry. At present, many antivirus products and technologies have been proposed, among which ultraviolet antivirus has been proven effective and does not pollute the environment. Most ultraviolet disinfection devices use fixed-point methods for disinfection, which is very labor-intensive and inflexible. Mobile ultraviolet disinfection robots are often not optimized because the movement trajectory of the robot is not optimized, resulting in insufficient disinfection areas. This study proposes a heuristic self-optimizing path planning algorithm called UV $^{\ast} $ . UV $^{\ast} $ generates a path trajectory based on the Boustrophedon pattern path planning to achieve full area coverage and then optimizes the path length of the robot’s movement trajectory through the path optimization procedure. This study compares the UV $^{\ast} $ algorithm, the Random method, the Boustrophedon pattern algorithm, the CIRCLES algorithm, and the genetic algorithm (GA). In UV $^{\ast} $ , we proposed a path optimization procedure that can optimize the existing path planning algorithms. The experimental results show that the UV $^{\ast} $ path planning algorithm can reach the goal of full coverage, and the total path length is shorter than that of the Random, CIRCLES, GA, and Boustrophedon pattern path planning algorithms.

In order to evaluate the effect of RRE on reducing blood lipid and protecting liver, a model of nonalcoholic fatty liver disease (NAFLD) mice induced by high-fat diet was used, and then the body weight, liver weight and liver coefficient of each group were calculated, and the TC、TG、HDL-C、LDL-C、AST、ALT、AKP were checked by sample test. The liver tissue was stained with HE and oil Red O for pathological observation and fat particles observation; Animal experiment results showed that RRE intervention could effectively improve the process of liver pathological changes, alleviate inflammatory injury and reduce the accumulation of liver fat particles in NAFLD mice; both high and medium doses of RRE could significantly reduce the levels of TC, TG and LDL-C in serum of NAFLD mice (P0.05); Through network pharmacology, the intersection of Rhinacanthus nasutus and NAFLD disease-related targets was carried out, and the effective active substances and action mechanism of RRE were predicted combined with molecular docking technology, which showed that rhinacanthin-C had good binding potential with the intersection targets. The experimental results showed that the RRE could reduce blood lipid, improved liver lipid deposition and inflammatory injury in NAFLD mice, so as to protect the liver. Its mechanism may be that the active substance rhinacanthin-C can improve liver lipid deposition and metabolic disorder through AMPK-SREBP1c-SIRT1 signal pathway. The experimental results can provide a scientific basis for the development of Zhuang medicine Rhinacanthus nasutus as a national drug for reducing blood lipid and improving fatty liver.

Orychophragmus violaceus (L.) O. E. Schulz (Brassicaceae) is widely distributed and plentiful in China and has been widely used for its application in ornamental, oil, ecology, foraging, and food. Recent studies have revealed that the main components of Orychophragmus violaceus include flavonoids, alkaloids, phenylpropanoids, phenolic acids, terpenoids, etc., which have pharmacological activities such as antioxidation, antiradiation, antitumor, hepatic protection, antiferroptosis, anti-inflammatory, and antibacterial. In this paper, the nutritional value, chemical compositions, pharmacological activity, and application value of Orychophragmus violaceus are summarized by referring to the relevant domestic and international literature to provide a reference for further research, development, and utilization of Orychophragmus violaceus in the future.

Paulownia tomentosa flower polysaccharide (PTFP) from dried cultured P. tomentosa flowers, is widely known for its immunomodulatory activities. Here, PTFP was extracted from Paulownia tomentosa flower using hot water extraction, followed by ethanol precipitation methods. Structural characterization of PTFP was revealed by scanning electron microscope, high-performance anion-exchange chromatography, gel chromatography, ultraviolet and infrared spectral. Meanwhile, adjuvant action of PTFT on the immune responses to classical swine fever vaccine in mice was evaluated to further proclaim the immune regulatory effect of PTFP. The results showed that PTFP was a type of heteropolysaccharide with a dense, rough surface and high molecular weight (667.02 kDa), mainly composed of glucose (30.93%), rhamnose (29.99%), galactose (15.66%), arabinose (6.95%), mannose (5.52%), and xylose (4.80%). The results of gel chromatography suggested that the molecular configuration of PTFP may be a spherical structure. The infrared spectrum results confirmed that the functional groups and chemical bond of PTFP contained -OH, O-H, C-H, C=O, C-O, etc. Moreover, PTFP exhibited obvious immune enhancement effect by improving concanavalin A (ConA), lipopolysaccharide (LPS), and CSFV E2-stimulated splenocyte growth and natural killer cell activity in CSFV-immunized mice. Similarly, the titers of CSFV E2-specific IgG, IgG1, IgG2a, and IgG2b antibodies and IFN-γ and IL-10 levels in CSFV-immunized mice were distinctly increased by PTFP treatment. Overall, PTFP was a macromolecular heteropolysaccharide primarily containing glucose and rhamnose, and possessed the auxiliary effect of immune enhancement on the immune responses to classical swine fever vaccine.

Staphylococcus aureus is a zoonotic opportunistic pathogen that represents a significant threat to public health. Previous studies have shown that tannic acid (TA) has an inhibitory effect on a variety of bacteria. In this study, the proteome and transcriptome of S. aureus were analyzed to comprehensively assess changes in genes and proteins induced by TA. Initial observations of morphological changes revealed that TA damaged the integrity of the cell membrane. Next, proteomic and genetic analyses showed that exposure to TA altered the expression levels of 651 differentially expressed proteins (DEPs, 283 upregulated and 368 downregulated) and 503 differentially expressed genes (DEGs, 191 upregulated and 312 downregulated). Analysis of the identified DEPs and DEGs suggested that TA damages the integrity of the cell envelope by decreasing the expression and protein abundance of enzymes involved in the synthesis of peptidoglycans, teichoic acids and fatty acids, such as murB, murQ, murG, fmhX and tagA. After treatment with TA, the assembly of ribosomes in S. aureus was severely impaired by significant reductions in available ribosome components, and thus protein synthesis was hindered. The levels of genes and proteins associated with amino acids and purine synthesis were remarkably decreased, which further reduced bacterial viability. In addition, ABC transporters, which are involved in amino acid and ion transport, were also badly affected. Our results reveal the molecular mechanisms underlying the effects of TA on S. aureus and provide a theoretical basis for the application of TA as an antibacterial chemotherapeutic agent.

ObjectiveTo analyze and evaluate the role of the High-throughput Drug Sensitivity (HDS) screening strategy in identifying highly sensitive drugs against esophageal squamous cell carcinoma (ESCC).MethodsA total of 80 patients with progressive ESCC were randomly divided into the observation (40 cases) and the control groups (40 cases). In the observation group, primary ESCC cells were isolated from the tumor tissues with a gastroscope, and drug sensitivity screening was performed on cells derived from the 40 ESCC cases using the HDS method, followed by verification in a patient-derived tumor xenograft (PDX) mouse model. Finally, the differences in the therapeutic efficacy (levels of CEA, CYFRA21-1, SCCA after chemotherapy and the rates of overall survival, local progression, and distant metastasis at 12 months and 18 months time points after chemotherapy) were compared between the observation group (Screened drug-treated) and the control group (Paclitaxel combined with cisplatin regimen-treated).ResultsForty ESCC patients were screened for nine different high-sensitive chemotherapeutics, with the majority showing sensitivity to Bortezomib. Experiments on animal models revealed that the tumor tissue mass of PDX mice treated with the HDS-screened drug was significantly lower than that of the Paclitaxel-treated mice (p

Objectives Amblyopia is the most common cause of unilateral visual impairment in children and requires long-term treatment. This study aimed to quantify the impact of pandemic control measures on amblyopia management.Design and setting This was a retrospective cohort study of data from a large amblyopia management database at a major tertiary eye care centre in China.Participants Outpatients with amblyopia who visited the hospital from 1 June 2019, through 28 February 2022.Primary and secondary outcome measures The primary outcome was the number of first and follow-up in-person visits to the hospital for amblyopia treatment. Secondary outcomes included the time interval between consecutive visits and improvement of vision (visual acuity, contrast sensitivity and stereopsis). Patient records were grouped into prepandemic and during pandemic periods.Results A total of 10 060 face-to-face visits for 5361 patients (median age 6.7 years, IQR 5.4, 8.9) that spanned two lockdown periods were included in the analysis, of which 28% were follow-up visits. Pandemic control measures caused a sharp decline in the number of outpatient visits (3% and 30% of prepandemic levels in the months directly after the start of the first (2020) and second (2021) periods of pandemic control measures, respectively). However, these drops were followed by pronounced rebounds in visits that exceeded prepandemic levels by 51.1% and 108.5%, respectively. The interval between consecutive visits increased significantly during the pandemic from a median (IQR) of 120 (112, 127) days in 2019 to 197 (179, 224) in 2020 (p

Monocular perceptual learning has shown promising performance in restoring visual function in amblyopes beyond the critical period in the laboratory. However, the treatment outcome is variable and indeterminate in actual clinical and neuroscientific practice. We aimed to explore the efficacy of monocular perceptual learning in the clinical setting. By combining continuous monitoring of perceptual learning and clinical measurements, we evaluated the efficacy and characteristics of visual acuity and contrast sensitivity function improvement and further explored the individualized effect after perceptual learning. Amblyopes (average age:17 ± 7 years old) were trained in a monocular two-alternative forced choice identification task at the 50% contrast threshold of the amblyopic eye for 10–15 days. We found that monocular perceptual learning improves both visual acuity and contrast sensitivity function in amblyopia. The broader activation of spatial contrast sensitivity, with a significant improvement in lower spatial frequencies, contributed to improving visual acuity. Visual acuity changes in the early stage can predict the endpoint treatment outcomes. Our results confirm the efficacy of monocular perceptual learning and suggest potential predictors of training outcomes to assist in the future management of clinical intervention and vision neuroscience research in amblyopia beyond the critical period of visual plasticity.

Objective: To investigate the dominant metabolic enzymes of six effective components (astragaloside IV, glycyrrhizic acid, calycosin-glucuronide, formononetin, ononin, calycosin-7-O-β-D- glucoside) of Huangqi Liuyi decoction extract (HQD).Methods: Mouse liver microsomes were prepared. The effects of specific inhibitors of CYP450 enzymes on the metabolism of six effective components of HQD were studied using liver microsomal incubation in vitro.Results: The chemical inhibitors of CYP2C37 inhibit the metabolism of glycyrrhizic acid and astragaloside IV. Formononetin and astragaloside IV metabolism is inhibited by the chemical inhibitors of CYP2C11. The chemical inhibitors of CYP2E1 and CYP1A2 inhibit the metabolism of calycosin-glucuronide. Chemical CYP3A11 inhibitors prevent formononetin and glycyrrhizic acid from being metabolized. However, no inhibitor significantly affected the metabolism of ononin and calycosin-7-O-β-D-glucoside.Conclusion: CYP2C37 may be involved in the metabolism of astragaloside IV and glycyrrhizic acid, the metabolism of astragaloside IV and formononetin may be related to CYP2C11, the metabolism of calycosin-glucuronide may be related to CYP1A2 and CYP2E1, and CYP3A11 may be involved in the metabolism of glycyrrhizic acid and formononetin. This research provides an experimental basis for exploring the pharmacokinetic differences caused by metabolic enzymes.

Using thermal storage materials with excellent thermal properties in the energy utilization system enables efficient use of renewable energy sources. Organic phase change materials (PCMs) have the advantages of high heat storage density, no corrosion, and low cost, but low thermal conductivity and insufficient heat transfer capacity have always been the bottlenecks in their application. In this paper, melamine foam@ reduction graphene oxide (MF@rGO) and carbon foam@ reduction graphene oxide (CF@rGO) composite foams with double carbon networks were prepared by self-assembly method and further employed in 1-octadecinal (OD) PCMs. The microstructure, chemical composition, phase change behavior, thermal conductivity, and photothermal conversion performance of MF@rGO/OD and CF@rGO/OD were studied in detail using SEM, FTIR, Raman DSC, and LFA. The melting and solidification enthalpies of CF@rGO/OD composite PCMs were 208.3 J/g and 191.4 J/g, respectively, its thermal conductivity increased to 1.54 W/m·K, which is 6.42 times that of pure OD. The porous structure and high thermal conductivity of the double carbon network substantially enhance the efficiency of energy storage and release in composite PCMs. CF@rGO/OD composite PCMs have excellent heat storage performance and heat transfer capacity, and a wide range of application prospects in the fields of low-temperature solar heat storage, precision instrument temperature control, and intelligent buildings.

The Poirier-Bienvenu neurodevelopmental syndrome (POBINDS) is a rare disease caused by mutations in the CSNK2B gene, which is characterized by intellectual disability and early-onset epilepsy. Mosaicism has not been previously reported in CSNK2B gene. POBINDS is autosomal dominant and almost all reported cases were de novo variants. Here, we report two patients were diagnosed with POBINDS. Using Whole Exome Sequencing (WES), we detected two novel CSNK2B variants in the two unrelated individuals: c.634_635del (p.Lys212AspfsTer33) and c.142C > T (p.Gln48Ter) respectively. Both of them showed mild developmental delay with early-onset and clustered seizures. The patient with c.634_635del(p.Lys212AspfsTer33) variant was mutant mosaicism, and the proportion of alleles in peripheral blood DNA was 28%. Further, the literature of patients with a de novo mutation of the CSNK2B gene was reviewed, particularly seizure semiology and genotype-phenotype correlations.

Sediment transport modeling for flows with cylinders is very challenging owing to the complicated flow–cylinder–sediment interactions, especially under the combined wave-current flows. In this paper, an improved formulation for incipient sediment suspension considering the effect of cylinder density (i.e., solid volume fraction) is employed to simulate the bottom sediment flux in the flow with cylinders. The proposed model is calibrated and validated using laboratory measurements under unidirectional and combined wave-current flows in previous studies. It is proved that the effects of cylinders on sediment suspension can be accounted for through a modified critical Shields number, and the proposed model is capable of simulating sediment suspension under both unidirectional and combined wave–current flows reasonably well with the average the coefficients of determination and model skills greater than 0.8 and 0.64.

Because of the lack of hydrological monitoring facilities and methods in many areas, basic hydrological elements cannot be obtained directly. In that case, the reverse flow routing method is frequently used, which allows for the simulation of hydraulic elements upstream using downstream data, and is of great significance for river and reservoir joint regulation, flood disaster management, flood control evaluation, and flood forecasting. The hydrological and hydrodynamic methods are the two main approaches to reverse flow routing. The hydrological method is mainly realized by constructing a distributed or lumped hydrological model based on rainfall, soil type, terrain slope, and other data. A distributed hydrological model focuses on the physical mechanism of runoff yield and flow concentration, the spatial variability of model input, and the hydraulic connection between different units. The solution of the hydrological method is relatively simple, but it requires a large amount of measured data, which limits the applicability of this method. The other method builds a hydrodynamic model by solving shallow water equations for reverse flow routing. This method has definite physical significance, higher accuracy, and obvious advantages of simple and fast calculations. It can not only simulate one-dimensional but also two-dimensional flood routing processes. In addition, the slope-area method is frequently used for flood reverse routing in many areas in China without relevant hydrological data, and can calculate the peak discharge, maximum water level, flood recurrence interval, and other information by the hydrodynamic formula, along with the cross-section and the measured flood mark water level. Due to the influence of extreme weather, a heavy rainstorm and flood occurred in the Luxi river basin in China on 16 August 2020, resulting in severe flood disasters in this area and causing significant economic losses. Moreover, due to the lack and damage of hydrological monitoring equipment, hydrological information such as flood hydrographs and peak discharges of this flood could not be recorded. To reduce the uncertainty of a single method for reverse flow routing, we integrated and applied the hydrodynamic, hydrological, and slope-area methods to reverse flow routing in the Luxi river basin on 16 August 2020. The simulation accuracy of the three methods was verified in terms of the measured flood mark water level, and the simulation results of the three methods were analyzed and compared. The results are as follows: 1) The hydrological method can better simulate flood hydrographs and durations, especially for flood hydrographs with multiple peaks, and is more applicable than the other two methods. However, the hydrodynamic and slope-area methods have better accuracy in the reverse simulation of flood peaks. Therefore, through the comprehensive comparative analysis of these three methods, flood elements such as flood hydrographs, peak discharges, and durations can be simulated more accurately, and the problem of large errors caused by a single method can be avoided; 2) The simulation results of the hydrodynamic and slope-area methods are similar, and the maximum error of the peak discharge calculated using the two methods is within 10%. According to the simulation results, the peak discharge reached 2,920 m3/s downstream of Luxi river basin, which is a flood having more than 100-year recurrence interval; 3) The simulation results of the hydrological method show that the flow hydrograph is a double-peak, and the two peaks occurred at 17:00 on August 16 and 6:00 on 17 August 2020, respectively.

Aim To develop and validate a risk assessment model (RAM) of venous thromboembolism (VTE) in hospitalized Chinese patients. Methods We reviewed data from 300 patients with VTE and 300 non-VTE patients at Beijing Shijitan Hospital. The risk factors related to VTE were analyzed, and the VTE RAM (Shijitan (SJT) version) was developed according to the weight of each risk factor. A total of 407 patients with VTE and 533 non-VTE patients were enrolled for external validation. The sensitivity, specificity, Youden index, receiver operating curve (ROC), and area under the ROC curve (AUC) were used to evaluate the performance of VTE RAM (SJT version) compared with Caprini RAM and Padua RAM. Results The VTE RAM (SJT version) contained six risk factors (age >60 years, lower limb edema, chronic obstructive pulmonary disease (COPD), central venous catheterization (CVC), VTE history, and D dimer). In the external validation group, for medical patients, the AUC value of SJT RAM (0.82 ± 0.03) is significantly higher than Caprini RAM (0.76 ± 0.04; P 0.05). For surgical patients, the AUC value of SJT RAM (0.72 ± 0.04) is significantly higher than the value of Padua RAM (0.66 ± 0.04; P 0.05). Conclusion The SJT RAM derived from general hospitalized Chinese patients will be time-saving for physicians and has a better predictive ability for patients at risk of VTE.

Abstract Renal fibrosis is the pathological outcome of most end‐stage renal diseases, yet there are still limited therapeutic options for it. In recent years, bone marrow mesenchymal stem cell‐derived exosomes (BM‐MSCs) have received much attention. Here, we investigate the therapeutic effect of BM‐MSCs on unilateral ureteral occlusion (UUO)‐induced interstitial fibrosis in the kidney by modulating prostaglandin E2 receptor 2 (EP2). Renal pathological changes were evident in the UUO group compared to the control group, with significantly increased expression of α‐smooth muscle actin (α‐SMA), fibronectin, Ep2 and F4/80+CD86+ and F4/80+CD206+ cells in the UUO group (p< 0.05). Pathological changes were alleviated and F4/80+CD86+ and F480/+CD206+ cells were reduced after exosome or EP2 agonist intervention compared to the UUO group. These data were further confirmed in vitro. Compared to the lipopolysaccharide (LPS) group and the LPS + exosome + Ah6809 group, the lipopolysaccharide (LPS) + exosome group and the LPS + butaprost group showed a significant decrease in α‐SMA expression, a decrease in the number of F4/80+CD86+ and F4/80+CD206+ cells, a decrease in interleukin (IL)‐6 and an increase in IL‐10 levels. Therefore, we conclude that BM‐MSCs can reduce the polarization of M1 and M2 macrophages by activating EP2 receptors, thereby ameliorating renal fibrosis.

IntroductionHere, we report the case of an infant suffering from Alagille syndrome (ALGS), manifesting with the atypical clinical manifestations of prenatal oligohydramnios and renal lesions. To the best of our knowledge, this is the first case of ALGS presenting as prenatal oligohydramnios and renal lesions caused by a de novo variant of the NOTCH2 gene.Case presentationA 3-month-old male infant was hospitalized for severe malnutrition. He presented with prenatal oligohydramnios from 28+4 weeks of gestation. After birth, he failed to thrive and suffered from impaired motor development, thermoregulation disorders, congenital bilateral renal hypodysplasia, which initially manifested as stage 5 before improving to stage 3 chronic renal impairment, slightly elevated levels of transaminases, cholestasis, and dysmorphic facial features. We used a diagnostic screening panel of 4,047 pathogenic genes and whole exome sequencing (WES) to analyze the proband and his parents (who had normal kidneys). We found that the proband carried a de novo heterozygous splicing variant (c.5930-2A > G) in intron 33 of the NOTCH2 gene. Transcriptome sequencing confirmed that the mutation of this gene site would affect the splicing of NOTCH2 mRNA and lead to exon 33 skipping.ConclusionsOur case expands the spectrum of pathogenic variants of the NOTCH2 gene that are known to be associated with ALGS and characterized by prenatal oligohydramnios and renal lesions. It also reminds us of the necessity to monitor the liver and kidney function of the infant if a mother has oligohydramnios during pregnancy and we recommend ALGS as an additional differential diagnosis in prenatal renal abnormalities.

Avian coccidiosis is a common enzootic disease caused by infection of Eimeria species parasites. It causes huge economic losses in the global poultry industry. Current control using anticoccidial drugs or vaccination is limited due to drug resistance and the relatively high cost of vaccines. Improving host genetic resistance to Eimeria species is considered an effective strategy for improved control of coccidiosis. Circular RNAs (circRNAs) have been found to function as biomarkers or diagnoses of various kinds of diseases. The molecular biological functions of circRNAs, miRNAs, and mRNAs related to Sasso chicken have not yet been described during Eimeria species challenge. In this study, RNA-seq was used to profile the expression pattern of circRNAs, miRNAs, and mRNAs in spleens from Eimeria tenella-infected and non-infected commercial dual-purpose Sasso T445 breed chickens. Results showed a total of 40 differentially expressed circRNAs (DEcircRNAs), 31 differentially expressed miRNAs (DEmiRNAs), and 820 differentially expressed genes (DEmRNAs) between infected and non-infected chickens. Regulatory networks were constructed between differentially expressed circRNAs, miRNAs, and mRNAs to offer insights into the interaction mechanisms between chickens and Eimeria spp. Functional validation of a significantly differentially expressed circRNA, circMGAT5, revealed that circMGAT5 could sponge miR-132c-5p to promote the expression of the miR-132c-5p target gene monocyte to macrophage differentiation-associated (MMD) during the infection of E. tenella sporozoites or LPS stimulation. Pathologically, knockdown of circMGAT5 significantly upregulated the expression of macrophage surface markers and the macrophage activation marker, F4/80 and MHC-II, which indicated that circMGAT5 might inhibit the activation of macrophage. miR-132c-5p markedly facilitated the expression of F4/80 and MHC-II while circMGAT5 could attenuate the increase of F4/80 and MHC-II induced by miR-132c-5p, indicating that circMGAT5 exhibited function through the circMGAT5-miR-132c-5p-MMD axis. Together, our results indicate that circRNAs exhibit their resistance or susceptive roles during E. tenella infection. Among these, circMGAT5 may inhibit the activation of macrophages through the circMGAT5-miR-132c-5p-MMD axis to participate in the immune response induced by Eimeria infection.

The gaseous molecule carbon monoxide (CO) can freely pass through the cell membrane and participate in signal transduction in the cell to regulate physiological activities in plants. Here, we report that CO has a positive regulatory role in stomatal development. Exogenous CO donor CORM-2 [Tricarbonyldichlororuthenium (II) dimer] treatment resulted in an increase of stomatal index (SI) on the abaxial epidermis of cotyledons in wild-type, which can be reversed by the addition of the CO biosynthesis inhibitor ZnPPIX [Protoporphyrin IX zinc (II)]. Consistent with this result, mutation of the CO biosynthesis gene HY1 resulted in a decrease of SI in hy1-100 plants, while overexpression of HY1 led to an increase of SI. Further investigation revealed that CO acts upstream of SPCH and YDA in the stomatal development pathway, since the loss of function mutants spch-1 and yda-2 were insensitive to CORM-2. The expression of EPF2 was inhibited by CORM-2 treatment in wild type and is lower in hy1 than in wild-type plants. In contrast, the expression of STOMAGEN was promoted by CORM-2 treatment and is higher in HY1-overexpression lines. Loss of function mutants of both epf2 and stomagen are insensitive to CORM-2 treatment. These results indicated that CO positively regulates stomatal initiation and distribution by modulating the expression of EPF2 and STOMAGEN.

ObjectiveTo identify factors associated with visual acuity regression following successful treatment of anisometropic amblyopia.Design and methodThis was a retrospective cohort study. Database records for 100 and 61 children with anisometropic amblyopia who met at least one criterion for successful treatment proposed by the Pediatric Eye Disease Investigator Group (PEDIG) and had at least 1 year of follow-up data available after the criterion was met were analyzed. The study sample was split into two groups, those who regressed within 1 year of successful treatment (no longer met any of the PEDIG criteria for successful treatment) and those who did not. A two-step analysis involving a least absolute shrinkage and selection operator (LASSO) regression and a logistic regression were used to identify predictor variables for increased risk of regression. A broad range of clinical, perceptual, and demographic variables were included in the analyses.ResultsSixty-eight (42.5%) children regressed within 1 year of successful treatment. Among the 27 predictor variables considered within the statistical modeling process, the three most important for predicting treatment regression were the extent of amblyopic eye visual acuity improvement, age at first hospital visit and sex. Specifically, lower risk of regression was associated with larger amblyopic eye visual acuity improvement with treatment, younger age at initiation of treatment and female sex.ConclusionPatients who received treatment at a younger age and responded well to treatment had a lower risk of treatment regression. This pattern of results suggests that early detection of amblyopia and strategies that enhance treatment adherence may reduce the risk of treatment regression. The higher risk of regression in boys than girls that we observed may reflect known sex differences in brain development and /or sex differences in environment within our sample of children from South China.

As an alternative chitosan source, edible insects have been proposed as an unconventional but viable option. Taking fly pupae as an example, this work performed chitosan extraction through a traditional chemical method with some modifications, and investigated its physicochemical properties and antimicrobial activity. The results showed that adding 0.5% sodium sulfite (Na2SO3, w/w, Na2SO3/fly pupae) synergized with sodium hydroxide (NaOH) for deproteinization was more effective than lye alone. Acid leaching was applied for desalination, and the optimal concentration of hydrochloric acid (HCl) was determined as 2 mol/L by ash content. For decoloration, the optimal decolorization oxidant was sodium hypochlorite (NaClO) with a concentration of 1.0%. For the deacetylation of chitin to chitosan, both the yield and degree of deacetylation (DD) using segmented treatment with alkali-NaOH were higher than those of traditional one-time deacetylation. The established physicochemical properties corresponded with the typical characteristics of chitosan. The determination of antimicrobial activity of chitosan by the turbidimetric method showed that chitosan exhibited notable activity in the order of Staphylococcus aureus > Escherichia coli > Saccharomyces cerevisiae, and this effect decreased with the increase in viscosity-average molecular weight (Mη). These results proved the viability of our improved method for the preparation of chitosan, a valuable antimicrobial agent, using an alternative natural source.

Coccidiosis is an economically significant protozoan disease and an intracellular parasite that significantly impacts poultry production. The gastrointestinal tract microbiota plays a central role in host health and metabolism, and these microbes enhance chickens’ immune systems and nutrient absorption. In this study, we analyzed the abundance and diversity of microbiota of the jejunum and cecum of a dual-purpose indigenous Horro chicken following Eimeria maxima infection. We compared microbial abundance, composition, and diversity at the 4- and 7- days post-infection using 16S rRNA gene sequencing. We obtained, on average, 147,742 and 132,986 high-quality sequences per sample for jejunum and cecum content, respectively. Firmicutes, Proteobacteria, Campilobacterota and Bacteroidota were the major microbial phylum detected in the jejunum content. Firmicutes were the dominant phylum for 4- and 7-days jejunum control groups accounting for (>60% of the sequences). In the infected group Campilobacterota was the dominant phylum in the jejunum (> 24% of sequences) at 4-and 7-days post-infection groups, while Proteobacteria was predominant at 4- and 7-days post-infection of the cecum (> 40% of the sequences). The microbial genus Lactobacillus and Helicobacter were found in the jejunum, while Alistipes, Barnesiella and Faecalibacterium were detected in the cecum. In the jejunum, Helicobacter was dominant at 4 -and-7 days post-infection (≥24%), and Lactobacillus was dominant at 4 -and 7- days in the control group (> 50%). In 4- and 7-days post-infection, Alistipes genus was the more prevalent (> 38%) in the cecum. Thus, clear differences were observed in the bacterial microbiota distribution and abundance between the jejunum and cecum, as well as between infected and control groups for both tissues. The results indicate that chicken intestinal microbial imbalance (dysbiosis) is associated with Eimeria parasite infection and will likely affect the host-microbial non-pathogenic and pathogenic molecular interactions.

Background: Several observational studies have demonstrated that significantly rising circulating adipokine levels are pervasive in preeclampsia or eclampsia disorder (or preeclampsia toxemia (PET)). However, it remains unclear whether this relationship is causal. In this study, we sought to elucidate the causal effects of circulating adipokine levels on PET.Methods: Summary-level data and independent genetic variants strongly associated with common adipokine molecule (adiponectin, leptin, resistin, sOB-R, and PAI-1) levels were drawn from public genome-wide association study (GWASs). Additionally, the corresponding effects between instrumental variables and PET outcomes were acquired from the FinnGen consortium, including 4,743 cases and 136,325 controls of European ancestry. Subsequently, an inverse-variance weighted (IVW) approach was applied for the principal two-sample Mendelian randomization (MR) and multivariable MR (MVMR) analyses. Various complementary sensitivity analyses were then carried out to determine the robustness of our models.Results: The results of the IVW method did not reveal any causal relationship shared across genetically predisposed adipokine levels and PET risk (for adiponectin, OR = 0.86, 95% CI: 0.65–1.13, p = 0.274). Additionally, no significant associations were identified after taking into account five circulating adipokines in MVMR research. Complementary sensitivity analysis also supported no significant associations between them. In the reverse MR analysis, genetically predicted PET risk showed a suggestive association with elevating PAI-1 levels by the IVW method (Beta = 0.120, 95% CI: 0.014, 0.227, p = 0.026). Furthermore, there were no strong correlations between genetic liability to PET and other adipokine levels (p > 0.05).Conclusion: Our MR study did not provide robust evidence supporting the causal role of common circulating adipokine levels in PET, whereas genetically predicted PET may instrumentally affect PAI-1 levels. These findings suggest that PAI-1 may be a useful biomarker for monitoring the diagnosis or therapy of PET rather than a therapeutic target for PET.

Abstract Background Nucleosome organization is involved in many regulatory activities in various organisms. However, studies integrating nucleosome organization in mammalian genomes are very limited mainly due to the lack of comprehensive data quality control (QC) assessment and uneven data quality of public data sets. Results The NUCOME is a database focused on filtering qualified nucleosome organization referenced landscapes covering various cell types in human and mouse based on QC metrics. The filtering strategy guarantees the quality of nucleosome organization referenced landscapes and exempts users from redundant data set selection and processing. The NUCOME database provides standardized, qualified data source and informative nucleosome organization features at a whole-genome scale and on the level of individual loci. Conclusions The NUCOME provides valuable data resources for integrative analyses focus on nucleosome organization. The NUCOME is freely available at http://compbio-zhanglab.org/NUCOME .

The purpose of this study was to investigate the effects of Huangqi Liuyi decoction extract (HQD) on diabetic nephropathy (DN), and the tissue distribution difference of six main active ingredients of HQD between normal and DN mouse models. DN mice were administered HQD for 12 weeks to investigate its efficacy in the treatment of DN. Liquid chromatography-tandem mass-spectrometry (HPLC-MS/MS) was used to analyze the tissue distribution of the six active ingredients of HQD in normal and DN mice, including astragaloside IV, calycosin-7-O-β-D-glucoside, calycosin glucuronide, ononin, formononetin, and glycyrrhizic acid. DN mice treated with HQD showed significantly decreased fasting blood glucose (FBG), 24-h urinary protein (24 h U-Alb), blood urea nitrogen (BUN), serum creatinine (Scr), and triglyceride levels (TG) (p < 0.05). Moreover, there were no significant differences in pharmacodynamics between HQD and Huangqi Liuyi decoction. Treated mice also had decreased expression of collagen I, ɑ–smooth muscle actin (ɑ-SMA), and vimentin; and upregulated expression of E-cadherin in their kidneys. Compared to normal mice, distributions of the six ingredients in the liver, heart, spleen, lungs, kidneys, stomach, small intestine, brain, and muscle of DN mice were different. The results indicated that the HQD could be used for the treatment of DN and to improve renal function. The pathological state of diabetic nephropathy may affect tissue distribution of HQD active ingredients in mice.

A growing body of research showed that diet management, such as promoting protein and vitamin intake and food restriction play a crucial role in extending time to morbidity and mortality in patients undergoing hemodialysis. However, the current dietary recommendations in nutrition guidelines lack examination of cultural factors. The study aimed to understand the diet influenced by culture in Chinese patients undergoing hemodialysis. Semi-structured interviews were conducted for 23 patients, aged 23–75 years, undergoing hemodialysis in a local tertiary hospital. Interview questions mainly focused on patients' real experience about diet, and their perceptions and attitudes toward diet. Each interview was digitally recorded, and conventional content analysis was used to attain information. The majority of patients reserved Chinese traditional dietary habits about salt and calcium intake. Although Chinese herbal medicine was not consumed, dietary therapy including brown sugar and dates was included in the participants' diet. Eggs, broth, and seafood were three prominent preferences and taboos profoundly impacted by culture. Additionally, Chinese social culture influenced patients' dietary behavior of eating at home and knowledge attainment. Diet in Chinese patients undergoing hemodialysis was still strongly influenced by culture. Culturally sensitive interventions regarding the improvement of diet intake are urgently needed.

Abstract Background Cryopreservation is an efficient way to store spermatozoa and is closely associated with the quality of sperm after the freeze-thaw process. During freeze-thaw cycling, excessive reactive oxygen species (ROS) are produced, and the effects of ROS on boar sperm during cryopreservation have not been identified. Results In this study, we evaluated the quality of boar spermatozoa in different steps of cryopreservation (extension, cooling, and thawing for 30 min and 240 min) with or without boar-sperm antioxidant (N-acetylcysteine (NAC)). The ROS levels, sperm motility, plasma membrane integrity, mitochondrial activity, sperm chromatin structure, ATP content, and sperm apoptosis were assayed. After thawing, the ROS level and sperm apoptosis were significantly increased, and the sperm motility, plasma membrane integrity, mitochondrial activity, sperm chromatin structure, and ATP content were significantly impaired compared with those at the extension period and cooling period. Moreover, the addition of N-acetyl L-cysteine (NAC) reversed these changes. Conclusion The freeze-thawing of boar spermatozoa impaired their motility, plasma membrane, mitochondrial activity, sperm chromatin structure and apoptosis by producing excessive ROS. Thus, the downregulation of ROS level by antioxidants, especially the NAC, is important for manufacturing frozen pig sperm to increase reproductive cells and livestock propagation, as well as to improve the application of frozen semen in pigs worldwide.

Abstract Sirtuin 1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase belonging to class III histone deacetylases. Previous studies have shown that SIRT1 is involved in kidney physiology regulation and protects the kidney from various pathological factors. However, the underlying mechanisms behind its function have yet to be fully elucidated. In our study, we found that ablation of Sirt1 in renal interstitial cells resulted in more severe renal damage and fibrosis in unilateral ureteral obstruction (UUO) model mice. We also observed that hypoxia-inducible factor (HIF)-2α expression was increased in Sirt1 conditional knockout mice, suggesting that HIF-2α might be a substrate of SIRT1, mediating its renoprotective roles. Therefore, we bred Hif2a deficient mice and subjected them to renal trauma through UUO surgery, ultimately finding that Hif2a ablation attenuated renal fibrogenesis induced by UUO injury. Moreover, in cultured NRK-49F cells, activation of SIRT1 decreased HIF-2α and fibrotic gene expressions, and inhibition of SIRT1 stimulated HIF-2α and fibrotic gene expressions. Co-immunoprecipitation analysis revealed that SIRT1 directly interacted with and deacetylated HIF-2α. Together, our data indicate that SIRT1 plays a protective role in renal damage and fibrosis, which is likely due to inhibition of HIF-2α.

Despite high global vaccination coverage, Newcastle disease (ND) remains a constant threat to poultry producers owing to low antibody levels. Given the respiratory mucosa is the important site for Newcastle disease virus (NDV) vaccination, enhancing respiratory mucosal immunity may help control ND. Our previous study showed that mulberry leaf polysaccharide (MLP) is very promising in delivering a robust balanced immune response, but the effects of it on respiratory immunity in chicks are unknown. In this study, we evaluated the potential of MLP to activate respiratory mucosal immunity and revealed the possible mechanism of MLP as an immunopotentiator for ND vaccines. Chicks were randomly divided into 5 groups: blank control, vaccination control (VC), and low-, middle-, and high-dose MLP (MLP-L, MLP-M, and MLP-H) (n = 30). The serum results of humoral and cell-mediated immune responses showed significant increases in NDV hemagglutination inhibition antibody titer, IgG and IgA antibody levels, and the T-lymphocyte population in the MLP-M group compared with the VC group. Validation of results also indicated remarkable increases in tracheal antibody-mediated immunity and a mucosal immune response in the MLP-M group. Furthermore, the upregulation of TLR7 revealed a possible mechanism. Our findings provided evidence to consider MLP as a potential mucosal vaccine adjuvant candidate against ND in chickens.

Abstract Background Hyperbilirubinemia after heart valve surgery (HVS) with cardiopulmonary bypass is frequently observed and associated with worse outcomes. We investigated the characteristics and prognosis of patients with severe hyperbilirubinemia after HVS for rheumatic heart disease (RHD) to identify the clinical outcomes and potential risk factors. Methods Between 2015 and 2018, patients who underwent HVS in the cardiac surgery intensive care unit of our hospital were retrospectively screened. Risk factors for acute kidney injury (AKI), the requirement for continuous renal replacement therapy (CRRT), and in-hospital and long-term mortality were identified by univariate and multivariate analyses. The patient survival proportion was graphically presented with the Kaplan–Meier method. Results A total of 149 patients who underwent HVS for RHD and had severe postoperative hyperbilirubinemia were included. Of the included patients, 80.5% developed postoperative AKI, and 18.1% required CRRT. The in-hospital mortality was 30.2%. Backward logistic regression analysis showed that the time to peak TB concentration (odds ratio [OR] 1.557, 95% confidence interval [CI] 1.259–1.926; P

Purpose Type B aortic dissection is a rare but life-threatening disease. Thoracic endovascular aortic repair (TEVAR) was widely used for Type B aortic dissection patients in the last decade due to the lower mortality and morbidity compared with open chest surgical repair (OCSR). AKI in type B aortic dissection is a well-recognized complication and indicates poor short-term and long-term outcome. The objective of this concise review was to identify the risk factors and the impact of AKI on type B aortic dissection patients. Methods and results A literature search was performed using PubMed, Embase, MEDLINE, and Cochrane Library with the search terms ‘type B aortic dissection’ and ‘acute kidney injury’ (AKI), and all English-language literatures published in print or available online from inception through August 2020 were thoroughly reviewed. Studies that reported relative AKI risks and outcomes in type B aortic dissection patient were included. Major mechanisms of AKI in type B aortic dissection included renal hypoperfusion, inflammation response, and the use of contrast medium. Type B aortic dissection patients with AKI significantly had increased hospital stay duration, need of renal replacement therapy, and 30-d and 1-year mortality. Conclusions AKI in type B aortic dissection is a well-recognized complication and associated with poor short-term and long-term outcome. Early identification of high-risk patients, early diagnosis of AKI, stabilization of the hemodynamic parameters, avoidance of nephrotoxic drugs, and optimization of the use of contrast agents are the major strategies for the reduction of AKI in type B aortic dissection patients.

Fibrotic diseases account for nearly half of all deaths in the developed world. Despite its importance, the pathogenesis of fibrosis remains poorly understood. Recently, the two mechanosensitive transcription cofactors YAP and TAZ have emerged as important profibrotic regulators in multiple murine tissues. Despite this growing recognition, a number of important questions remain unanswered, including which cell types require YAP/TAZ activation for fibrosis to occur and the time course of this activation. Here, we present a detailed analysis of the role that myofibroblast YAP and TAZ play in organ fibrosis and the kinetics of their activation. Using analyses of cells, as well as multiple murine and human tissues, we demonstrated that myofibroblast YAP and TAZ were activated early after organ injury and that this activation was sustained. We further demonstrated the critical importance of myofibroblast YAP/TAZ in driving progressive scarring in the kidney, lung, and liver, using multiple transgenic models in which YAP and TAZ were either deleted or hyperactivated. Taken together, these data establish the importance of early injury-induced myofibroblast YAP and TAZ activation as a key event driving fibrosis in multiple organs. This information should help guide the development of new antifibrotic YAP/TAZ inhibition strategies.

Huangqi Liuyi decoction is a famous traditional Chinese medicine (TCM) that has been widely used in China for the management of diabetes since the Song Dynasty. Today, it is commonly used for treating diabetic nephropathy (DN). Our previous experimental studies have suggested that the mixture HQD, containing astragalus saponin, astragalus flavone, astragalus polysaccharide, and glycyrrhetinic acid, could be used for the treatment of DN and to improve renal function. The objective of this study was to develop a sensitive and reliable high-performance liquid chromatography-tandem mass spectrometry method for simultaneous quantitation of astragaloside IV, calycosin-7-O-β-D-glucoside, calycosin-glucuronide, ononin, formononetin, and glycyrrhizic acid, which are the main active constituents in HQD, and to compare the pharmacokinetics of these active constituents in control and DN mice orally treated with HQD. The results indicated that the pharmacokinetic parameters of HQD were significantly different between the control and DN mouse groups. The absorption of HQD in the DN mice was greater than that in control mice.

Mycotoxins can accumulate in various feeds and thus may get in duck meat, which may have severe food safety and public health implications. This study examined mycotoxins and veterinary medications in duck meat marketed in eight marketplaces around China. For the determination of mycotoxins, including the mycotoxins aflatoxin B1 (AFB1), aflatoxin B2 (AFB2), aflatoxin M1 (AFM1), T-2 toxin, zearalenone (ZEN), and ochratoxin A (OTA), a liquid-chromatography tandem mass spectrometry (LC-MS/MS) method was validated. Overall, 13 out of 48 samples (27%) presented AFB1, and AFB2 was present in 14 out of 48 samples with positive levels ranging from 0.5 μg/kg (gizzard) to 4.1 μg/kg (lung). Eleven samples were contaminated with AFM1. T-2 was also found in three parts of duck samples (duck gizzard, neck, and lung), and the 5th and 48th samples were contaminated with T-2. ZEN was found in 5 of 48 analyzed samples (10%), and OTA was present in 21 out of 48 samples. The maximum kinds of mycotoxins found simultaneously in duck samples were six in duck lungs. High co-occurrence of mycotoxins was verified in several samples. The detection rate of various veterinary drugs was 0–12.5% in duck meat samples, and the over standard rate was 2.1%. Co-occurrence of veterinary drugs was verified in several samples.

Abstract Background Hyperbilirubinemia is one of the common complications after cardiac surgery and is associated with increased mortality. However, to the best of our knowledge, the reports on clinical significance of postoperative severe hyperbilirubinemia in Stanford type A aortic dissection (AAD) patients were limited. Methods Patients who underwent surgical treatment for AAD in our center between January 2015 and December 2018 were retrospectively screened. In-hospital mortality, long-term mortality, acute kidney injury (AKI), and the requirement of continuous renal replacement therapy (CRRT) were assessed as endpoints. Univariate and multivariate regression models were employed to identify the risk factors of these endpoints. Results After screening, 271 patients were included in our present study. Of the included patients, 222 (81.9%) experienced postoperative AKI, and 50 (18.5%) received CRRT. The in-hospital mortality was 30.3%. The 1-year, 2-year, and 3-year cumulative mortality were 32.9, 33.9, and 35.3%, respectively. Multivariate Logistic regression analysis indicated that age (P

BackgroundIncreased uric acid (UA) levels have been reported to be associated with poor clinical outcomes in several conditions. However, the prognostic value of UA in patients with infective endocarditis (IE) is yet unknown.MethodsA total of 1,117 patients with IE were included and divided into two groups according to the current definition of hyperuricemia (UA>420 μmol/L in men and >360 μmol/L in women): hyperuricemia group (n=336) and normouricemia group (n=781). The association between the UA level and short-term outcomes were examined.ResultsThe in-hospital mortality was 6.2% (69/1117). Patients with hyperuricemia carried a higher risk of in-hospital death (9.8% vs. 4.6%, p=0.001). Hyperuricemia was not an independent risk factor for in-hospital death (adjusted odds ratio [aOR]=1.92, 95% confidence interval [CI]: 0.92-4.02, p=0.084). A U-shaped relationship was found between the UA level and in-hospital death (p400 and 400 μmol/L (adjusted hazard ratio [aHR]=3.54, 95%CI: 1.77-7.07, p

The accurate evaluation method of LID toward the attenuation of urban flood is still a hot issue. This paper focuses on a coupled 1D and 2D hydrodynamic model, investigating the model parameters set in a collapsible loess area, and the changes in the surface runoff, waterlogged area, and drainage network indicators under different rainfall patterns. The results show that the coupled model can effectively simulate the effect of LID facilities under unaltered and retrofitted conditions. It is found that the infiltration parameters in a collapsible loess area are higher than in other eastern cities by calibration and validation. After implementing the LID facilities, the total runoff, peak flood flow, waterlogged area, runoff coefficient, and drainage pressure under different rainfall patterns have all been reduced. With the increases in the rainfall return period, the waterlogging reduction effect of LID facilities would gradually weaken. The rainfall return period has a great impact on the indicators of surface runoff, waterlogged area, and drainage capacity. The coefficient of rainfall peak has a relatively big impact on indicators of pipelines, such as the proportion of overflow nodes, the proportion of fully loaded pipelines, and the average full-load duration. The rainfall duration has a major impact on the total runoff quantity, runoff coefficient, and average full-load duration.

Mulberry leaf polysaccharide (MLP) possess many biological characteristics, such as immunomodulatory and antioxidant properties, but whether MLP can impact the distribution and characteristics of the gut microbiota is not yet clear. In this study, the effects of MLP on diversity- and immune-related factors and short-chain fatty acids (SCFAs) of the gut microbiota in mice were investigated. The results showed that MLP could restore the indexes of the thymus and spleen, the damaged intestinal barrier and levels of inflammatory cytokines in cyclophosphamide (CTX)-treated mice, and alleviate oxidative damage to the liver. Additionally, MLP were associated with a relatively higher abundance of Bacteroidetes but lower levels of Firmicutes, Butyricimonas and Eubacterium in CTX-treated mice. Moreover, MLP restored the levels of acetic acid, propionic acid, and n-butyric acid reduced by CTX. These results indicated that MLP, as a special ingredient, might regulate the immune response by altering the spatial structure of the gut microbiota and the production of SCFAs.

Sichuan Basin is the only successful basin for shale gas exploration in China. In addition to the main shale in the Lower Silurian Longmaxi formation, the lower Cambrian Qiongzhusi shale is an important potential formation. However, it was once considered that shale gas is difficult to enrich because of its poor sealing conditions and hydrocarbon migration to adjacent reservoirs. With the increasing research on hydrocarbon generation and reservoir in shale of Qiongzhusi Formation in recent years, it has become an important exploration target in Sichuan Basin. The enrichment of oil and gas is closely related to fluid activities. Limited by the degree of exploration, there is little analysis of fluid activities in Qiongzhusi Formation, and there is little analysis of shale gas enrichment potential from the perspective of fluid. The hydrocarbon generated from Qiongzhusi shale in the rift could migrate laterally to the uplift area and form a reservoir in Dengying Formation. The fluid activities from source rock to reservoir are basically the same. Therefore, this paper reconstructed the history of hydrocarbon activities in Dengying reservoirs based on fluid inclusion analysis. Then the fluid activity process in Qiongzhusi shale was studied, and its enrichment conditions of shale gas was discussed. The results show that the hydrocarbon activities of Dengying Formation can be divided into three stages: 1) oil charging stage, 2) oil cracking gas generation stage and 3) gas reservoir adjustment stage. The first stage is under normal pressure, and the second and third stages developed overpressure with pressure coefficients of 1.3 and 1.2, respectively. High pressure coefficient is an important indicator of shale gas enrichment. Because the source rock of Qiongzhusi Formation has always been the main source rock of Dengying Formation, it can supply hydrocarbon to Dengying Formation only with overpressure in gas generation stage. Therefore, overpressure in the last two stages of gas generation indeed existed. As long as the sealing condition of shale itself is not particularly poor, shale gas “sweet points” would be formed. Therefore, the thick shale in Deyang-Anyue rift is the focus of shale gas exploration in Qiongzhusi Formation.