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AIM: To investigate systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) levels in patients with type 2 diabetes at different stages of diabetic retinopathy (DR). METHODS: This retrospective study included 141 patients with type 2 diabetes mellitus (DM): 45 without diabetic retinopathy (NDR), 47 with non-proliferative diabetic retinopathy (NPDR), and 49 with proliferative diabetic retinopathy (PDR). Complete blood counts were obtained, and NLR, PLR, and SII were calculated. The study analysed the ability of inflammatory markers to predict DR using receiver operating characteristic (ROC) curves. The relationships between DR stages and SII, PLR, and NLP were assessed using multivariate logistic regression. RESULTS: The average NLR, PLR, and SII were higher in the PDR group than in the NPDR group (P=0.011, 0.043, 0.009, respectively); higher in the NPDR group than in the NDR group (P

Abstract Background An idiopathic macular hole (IMH) is a full-thickness anatomic defect extending from the internal limiting membrane to the photoreceptor layer of the macula without any known cause. Recently, clinical laboratory markers of systemic inflammatory status derived from complete blood counts have been evaluated in ocular diseases. This study aimed to explore whether they could predict the development and progression of IMHs. Methods A retrospective review of 36 patients with IMH and 36 sex-and-age-matched patients with cataracts was conducted. We collected complete blood counts of all participating individuals and calculated systemic immunoinflammatory indicators. The maximum base diameter of the IMH (BD), minimum diameter of the IMH (MIN), height of the IMH (H), area of the intraretinal cyst (IRC), and curve lengths of the detached photoreceptor arms were measured on optical coherence tomography (OCT) images. We used these values to calculate the macular hole index (MHI), tractional hole index (THI), diameter hole index (DHI), hole form factor (HFF), and macular hole closure index (MHCI). We performed a receiver operating characteristic (ROC) curve analysis of 30 patients with IMH who were followed up 1 month after surgery. Results Lymphocyte counts were significantly higher in the IMH group. No other significant differences were observed between the IMH and control groups. Lymphocyte counts in the IMH group were significantly negatively correlated with MIN and BD and were significantly positively correlated with MHI, THI, and MHCI. However, lymphocyte counts were not significantly correlated with H, IRC, DHI, and HFF. In the ROC analysis, BD, MIN, MHI, THI, and MHCI were significant predictors of anatomical outcomes. According to the cut-off points of the ROC analysis, lymphocyte counts were compared between the above-cut-off and below-cut-off groups. Lymphocyte counts were significantly higher in the MIN ≤ 499.61 μm, MHI ≥ 0.47, THI ≥ 1.2, and MHCI ≥ 0.81 groups. There were no significant differences between the above-cut-off and below-cut-off BD groups. Conclusions Although inflammation may not be an initiating factor, it may be involved in IMH formation. Lymphocytes may play a relatively important role in tissue repair during the developmental and postoperative recovery phases of IMH.

Abstract Evidence from Europe shows that perioperative chemotherapy may be beneficial for the treatment of locally advanced gastric cancer, but reliable and robust data is lacking. To rectify this, the phase 3 RESONANCE trial investigated the efficacy and safety of S-1 plus oxaliplatin (SOX) as a perioperative chemotherapy regimen for gastric cancer. This randomized, open-label trial enrolled patients from 19 medical centers with stage II/III resectable gastric cancer who were centrally randomly assigned to either perioperative chemotherapy (PC) arm or adjuvant chemotherapy (AC) arm. Patients in the PC arm received two to four cycles of SOX followed by surgery and four to six cycles of SOX. Patients in the AC arm received upfront surgery and eight cycles of SOX. 386 patients in each group were enrolled and 756 (382 in PC and 374 in AC) were included in the mITT population. The three-year DFS rate was 61.7% in the PC arm and 53.8% in the AC arm (log-rank p = 0.019). The R0 resection rate in the PC arm was significantly higher than that in the AC arm (94.9% vs. 83.7%, p

BackgroundChidamide is subtype-selective histone deacetylase (HDAC) inhibitor that showed promising result in clinical trials to improve prognosis of angioimmunoblastic T-cell lymphoma (AITL) patients. However, in real world settings, contradictory reports existed as to whether chidamide improve overall survival (OS). Therefore, we aimed to develop an interpretable machine learning (Machine learning)–based model to predict the 2-year overall survival of AITL patients based on chidamide usage and baseline features.MethodsA total of 183 patients with AITL were randomly divided into training set and testing set. We used 5 ML algorithms to build predictive models. Recursive feature elimination (RFE) method was used to filter for the most important features. The ML models were interpreted and the relevance of the selected features was determined using the Shapley additive explanations (SHAP) method and the local interpretable model–agnostic explanationalgorithm.ResultsA total of 183 patients with newly diagnosed AITL from 2012 to 2022 from 3 centers in China were enrolled in our study. Seventy-one patients were dead within 2 years after diagnosis. Five ML algorithms were built based on chidamide usage and 16 baseline features to predict 2-year OS. Catboost model presented to be the best predictive model. After RFE screening, 12 variables demonstrated the best performance (AUC = 0.8651). Using chidamide ranked third among all the variables that correlated with 2-year OS.ConclusionThis study demonstrated that the Catboost model with 12 variables could effectively predict the 2-year OS of AITL patients. Combining chidamide in the treatment therapy was positively correlated with longer OS of AITL patients.

Lactylation is a novel post-translational modification (PTM) involving proteins that is induced by lactate accumulation. Histone lysine lactylation alters chromatin spatial configuration, influencing gene transcription and regulating the expression of associated genes. This modification plays a crucial role as an epigenetic regulatory factor in the progression of various diseases. Glycolytic reprogramming is one of the most extensively studied forms of metabolic reprogramming, recognized as a key hallmark of cancer cells. It is characterized by an increase in glycolysis and the inhibition of the tricarboxylic acid (TCA) cycle, accompanied by significant lactate production and accumulation. The two processes are closely linked by lactate, which interacts in various physiological and pathological processes. On the one hand, lactylation levels generally correlate positively with the extent of glycolytic reprogramming, being directly influenced by the lactate concentration produced during glycolytic reprogramming. On the other hand, lactylation can also regulate glycolytic pathways by affecting the transcription and structural functions of essential glycolytic enzymes. This review comprehensively outlines the mechanisms of lactylation and glycolytic reprogramming and their interactions in tumor progression, immunity, and inflammation, with the aim of elucidating the relationship between glycolytic reprogramming and lactylation.

Summary: The nexus between environmental pollution (EP) and technological innovation is crucial for achieving sustainable development. However, existing literature has paid less attention to the new form of high-quality innovation (HI) in environmental management. This paper uses panel data from 31 Chinese provinces from 2008 to 2020, employing the two-stage least squares method to investigate the relationship between HI and EP. The empirical results reveal that HI can effectively reduce the EP, which holds after multiple robustness tests, and this effect is more obvious in southern China. Meanwhile, HI drives clean and efficient energy transition and decreases EP. Moreover, increased environmental regulation weakens the influence of HI on EP. The major contributions of this study are constructing an HI index including innovation, human capital, and government support and examining its influence on EP in China. The findings encourage government to implement policies of innovation-driven transformation, energy conservation and emissions reduction.

Abstract Background Although oral hygiene is closely related to various diseases, it is sub-optimal in the Intensive Care Unit (ICU). Oral care in the ICU is challenged by nursing workloads, low staffing, and higher acuity patients, there are few policies and written guidelines for oral care. Nurses often delegate oral care to nursing assistants (NAs) whose role is overlooked. This study is to explore the perspectives, obstacles, and challenges of NAs in the oral care of the ICU. Methods A qualitative study and semi-structured interviews were conducted with NAs in three ICU units, and Colaizzi’s phenomenological method was used to analyze the records. Results Initially, 13 NAs met the inclusion criteria, and two did not participate in this study as they refused to be recorded. Finally, 11 ICU NAs were interviewed, with three receiving face-to-face interviews and eight receiving telephone interviews. Using Colaizzi’s phenomenological method, two themes and eight subthemes emerged from the data, we examined the self-perception, barriers and challenges of NAs regarding oral care and identified the subthemes: (1) The target audience, frequency, and importance; (2) Role; (3) Evaluation; (4) Patient-related factors; (5) Oral care tools; (6) Psychology of NAs; (7) Lack of education and training; (8) Lack of team support. Conclusion Nursing assistants whose roles are overlooked by the nursing team are important members of the ICU team. Though oral care is closely related to disease prevention, it is rarely considered an essential task. Major barriers to implementing oral care in the ICU environment and patients include the psychological quality of participants, non-standard education and training, and inadequate team support. The expectation is that medical personnel will prioritize oral hygiene and recognize the significance of NAs in nursing work. Furthermore, future ICU oral care should investigate suitable tools and mouthwashes, simplified and standardized processes, standardized training, and multidisciplinary team collaboration.

Abstract Objective This study assessed the predictive value of electrical activity of the diaphragm (EAdi) and the EAdi-derived monitoring index in the prognosis of patients with severe cerebral hemorrhage. Methods Ninety patients with severe cerebral hemorrhage were admitted to the Neurosurgery Intensive Care Unit of Yijishan Hospital from April 2019 to June 2021 and were divided into the good prognosis group (Glasgow Outcome Scale [GOS] ≥ 4) and poor prognosis group (GOS ≤ 3). The receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to evaluate prediction accuracy. Results EAdi, neuro-ventilatory efficiency (NVE), and neuro-muscular efficiency (NME) in patients with good prognosis were significantly higher than those in patients with poor prognosis (4.707 µV vs 2.80 µV, P

Abstract At present, the separation technology of fluorite and calcite is still immature, and the research in this paper can promote the improvement of the separation technology of fluorite and calcite. The selective inhibition mechanism of tannin and humate sodium on calcite was studied by means of actual ore flotation test, single mineral flotation test, Zeta potential measurement and FT-IR spectroscopy. The results show that the mixture of tannin and sodium humate inhibitor has a good inhibitory effect on carbonate under weak alkaline condition. The reaction products of sodium humate, tannin and calcium ions in solution interact with organic compounds adsorbed on the surface of calcite, forming multilayer adsorption on the surface of calcite, making calcite more hydrophilic. Based on density functional theory, Materials Studio (MS) was used to calculate the relevant adsorption energy, and the result was as follows: (a) compared with fluorite, tannin and humate sodium molecules are more easily adsorbed on the surface of calcite. (b) Compared with calcite alone adsorption of tannin molecules or sodium humate molecules, the adsorption state will be more stable, and the effect of tannin and sodium humate synergistic inhibition of calcite is better than the effect of inhibition alone. Therefore, using tannin and sodium humate as a combination inhibitor can effectively separate fluorite and calcite, which will promote the development and utilization of fluorite ore in industry.

Abstract Evaluation of chemical drug-likeness is essential for the discovery of high-quality drug candidates while avoiding unwarranted biological and clinical trial costs. A high-quality drug candidate should have promising drug-like properties, including pharmacological activity, suitable physicochemical and ADMET properties. Hence, in silico prediction of chemical drug-likeness has been proposed while being a challenging task. Although several prediction models have been developed to assess chemical drug-likeness, they have such drawbacks as sample dependence and poor interpretability. In this study, we developed a novel strategy, named DBPP-Predictor, to predict chemical drug-likeness based on property profile representation by integrating physicochemical and ADMET properties. The results demonstrated that DBPP-Predictor exhibited considerable generalization capability with AUC (area under the curve) values from 0.817 to 0.913 on external validation sets. In terms of application feasibility analysis, the results indicated that DBPP-Predictor not only demonstrated consistent and reasonable scoring performance on different data sets, but also was able to guide structural optimization. Moreover, it offered a new drug-likeness assessment perspective, without significant linear correlation with existing methods. We also developed a free standalone software for users to make drug-likeness prediction and property profile visualization for their compounds of interest. In summary, our DBPP-Predictor provided a valuable tool for the prediction of chemical drug-likeness, helping to identify appropriate drug candidates for further development.

Image stitching is one of the research hotspots in the fields of computer vision and image processing. Existing methods typically use traditional algorithms or deep learning-based algorithms to achieve this task. However, traditional image stitching algorithms perform poorly in images with weak textures, dark light and multiple noises. And the convolutional neural network (CNN) used by deep learning image stitching algorithms is difficult to capture the global contextual information of an image, resulting in limited accuracy. To address this issue, we designed a Multi-Grid Homography Estimation Network (MGHE-Net) based on Transformers. This network consists of cross-image integration feature extraction module, image matching module, and offset refinement module. The powerful global modeling capability of the Transformer is used to achieve multi-grid homography estimation from coarse to fine, improving the accuracy of image stitching. Experimental results demonstrate that our network not only achieves better stitching results in images with weak textures and dark light, but also reduces errors by 75.3% and 65.1%, respectively, compared to traditional algorithms and CNN-based algorithms on datasets with large parallax. Furthermore, our network improves the efficiency of image stitching.

Abstract In order to facilitate the analysis and processing of optical signals, an FPGA-based CCD signal acquisition and data transmission system is designed in this work. The system uses an FPGA as the main control device, the TCD1304DG/AP chip as the optical signal detector, and the CYUSB3KIT-003 development board product by Cypress for data transmission. Verilog and Python languages are employed for modular design and on-board verification. Through the coordination of each module, the system successfully achieves CCD signal data acquisition and transmission.

Angiogenesis is the growth of new blood vessels on preexisting ones. It is the outcome of a multifactorial effect involving several cells, which can be brought on by different stress reactions.The accumulation of unfolded proteins in the endoplasmic reticulum occurs when cells are stressed due to environmental changes, where physical or chemical stimuli induce endoplasmic reticulum stress, thereby activating the unfolded protein response (UPR), a homeostasis response designed to re-establish protein balance. Ferroptosis is a planned death of lipid peroxidation and anomalies in metabolism that is dependent on iron. Large concentrations of iron ions accumulate there, along with high concentrations of lipid peroxides and reactive oxygen species, all of which can contribute to the development of several diseases. Through the production of growth factors, adhesion factors, and inflammatory factors that trigger the start of angiogenesis, both UPR and Ferroptosis can be implicated in angiogenesis.To set the stage for further research on angiogenesis, this work concentrated on the effects of Ferroptosis and UPR on angiogenesis, respectively.

Abstract One-dimensional (1D) nanomaterials have sparked widespread research interest owing to their fascinating physicochemical properties, however, the direct self-assembly of 1D porous nanomaterials and control over their porosity still presents a grand challenge. Herein, we report a monomicelle oriented self-assembly approach to fabricate 1D mesoporous nanostructures with uniform diameter, high aspect ratio and ordered mesostructure. This strategy features the introduction of hexamethylenetetramine as a curing agent, which can subtly control the monomicelle self-assembly kinetics, thus enabling formation of high-quality 1D ordered mesostructures. Meanwhile, the micellar structure can be precisely manipulated by changing the reactant stoichiometric ratio, resulting in tailorable mesophases from 3D cubic (Im-3m) to 2D hexagonal (p6mm) symmetries. More interestingly, the resultant mesoporous nanofibers can be assembled into 3D hierarchical cryogels on a large scale. The 1D nanoscale of the mesoporous nanofibers, in combination with small diameter (~65 nm), high aspect ratio (~154), large surface area (~452 m2 g−1), and 3D open mesopores (~6 nm), endows them with excellent performances for sodium ion storage and water purification. Our methodology opens up an exciting way to develop next-generation ordered mesoporous materials for various applications.

Abstract Objectives Ultrasound (US) technology has recently made advances that have led to the development of modalities including elastography and contrast-enhanced ultrasound. The use of different US modalities in combination may increase the accuracy of PCa diagnosis. This study aims to assess the diagnostic accuracy of multiparametric ultrasound (mpUS) in the PCa diagnosis. Methods Through September 2023, we searched through Cochrane CENTRAL, PubMed, Embase, Scopus, Web of Science, ClinicalTrial.gov, and Google Scholar for relevant studies. We used standard methods recommended for meta-analyses of diagnostic evaluation. We plot the SROC curve, which stands for summary receiver operating characteristic. To determine how confounding factors affected the results, meta-regression analysis was used. Results Finally, 1004 patients from 8 studies that were included in this research were examined. The diagnostic odds ratio for PCa was 20 (95% confidence interval (CI), 8–49) and the pooled estimates of mpUS for diagnosis were as follows: sensitivity, 0.88 (95% CI, 0.81–0.93); specificity, 0.72 (95% CI, 0.59–0.83); positive predictive value, 0.75 (95% CI, 0.63–0.87); and negative predictive value, 0.82 (95% CI, 0.71–0.93). The area under the SROC curve was 0.89 (95% CI, 0.86–0.92). There was a significant heterogeneity among the studies (p

Ammonium inhibition is a key limiting factor for anaerobic digestion when using chicken manure as the main substrate, especially in a digestion system with biogas slurry reflux. Air stripping is usually used as a recycled biogas slurry treatment. In this study, we carried out the anaerobic co-digestion of chicken manure and corn straw. The fermentation performance was investigated with and without air stripping at different biogas slurry reflux ratios and with an increasing organic loading rate. The results show that air stripping enhanced biogas production, system stability, and volatile solid removal efficiency via the mitigation control of ammonium inhibition. The total ammonium nitrogen in the digesters with air stripping was 20.24–46.40% lower than in those without air stripping. The highest specific biogas production and volatile solid removal efficiency values were obtained in the digesters at an organic loading rate of 3.3 g volatile solid (VS)/(L·d) and a reflux ratio of 75% with air stripping, reaching 480.43 mL/gVSadd and 63.36%, respectively. Moreover, air stripping also improved the organic loading rate and reflux ratio. Stable operation was achieved at an organic loading rate of 5.3 gVS/(L·d) and a reflux ratio of 75%, with specific biogas production of 392.35 mL/gVSadd and a volatile solid removal efficiency of 50.33%. The fermentation performance deteriorated when the organic loading rate was increased to 8.0 gVS/(L·d) at a reflux ratio of 75%, even when air stripping was conducted, indicating that a slighter lower reflux ratio (50%) could be more feasible at a higher organic loading rate (8.0 gVS/(L·d). Additionally, the methanogen community structure varied according to the use of air stripping, with a shift in the methanogenic pathway from hydrogenotrophic to acetoclastic methanogens. Overall, our findings support the adoption of air stripping for ammonium mitigation in anaerobic digestion with biogas slurry reflux.

Ubiquitination, a post-translational modification, refers to the covalent attachment of ubiquitin molecules to substrates. This modification plays a critical role in diverse cellular processes such as protein degradation. The specificity of ubiquitination for substrates is regulated by E3 ubiquitin ligases. Dysregulation of ubiquitination has been associated with numerous diseases, including cancers. In our study, we first investigated the protein expression patterns of E3 ligases across 12 cancer types. Our findings indicated that E3 ligases tend to be up-regulated and exhibit reduced tissue specificity in tumors. Moreover, the correlation of protein expression between E3 ligases and substrates demonstrated significant changes in cancers, suggesting that E3-substrate specificity alters in tumors compared to normal tissues. By integrating transcriptome, proteome, and ubiquitylome data, we further characterized the E3-substrate regulatory patterns in lung squamous cell carcinoma. Our analysis revealed that the upregulation of the SKP2 E3 ligase leads to excessive degradation of BRCA2, potentially promoting tumor cell proliferation and metastasis. Furthermore, the upregulation of E3 ubiquitin–protein ligase TRIM33 was identified as a biomarker associated with a favorable prognosis by inhibiting the cell cycle. This work exemplifies how leveraging multi-omics data to analyze E3 ligases across various cancers can unveil prognosis biomarkers and facilitate the identification of potential drug targets for cancer therapy.

Background:Previous studies have shown that the lateral femoral condyle ratio (LFCR) measured by X-ray has a significant relationship with the anterior cruciate ligament (ACL) injury. However, few relevant studies have been performed on LFCR measured by magnetic resonance imaging (MRI).Purpose:(1) To evaluate the relationship between LFCR measured by MRI and ACL injury or rerupture. (2) To compare the LFCR measured by MRI with existing bony morphological risk factors and screen out the most predictive risk factors for primary ACL injury or rerupture.Study Design:Cohort study; Level of evidence, 3.Methods:Totally 147 patients who underwent knee arthroscopic surgery from 2015 to 2019 with minimum follow-up of 48 months were retrospectively evaluated. Patients were placed into three groups: 1) the control group of patients with simple meniscus tears without ligament injury; 2) the primary noncontact ACL injury group; 3) ACL rerupture group (ACL reconstruction failure). The LFCR measured by MRI and other previous known risk factors associated with MRI (notch width index, medial tibial slope, lateral tibial slope, medial tibial depth, lateral tibial height) were performed to evaluate their predictive value for ACL injury and rerupture. All the risk factors with p < 0.01 according to univariate analysis were included in the logistic regression models. Receiver operating characteristic (ROC) curves were analyzed for sensitivity, specificity, cut-off, and area under the curve (AUC). Z tests were used to compare the AUC values.Results:The LFCR measured by MRI was obviously higher in primary ACL injury group (0.628 ± 0.020) and in ACL rerupture group (0.625 ± 0.021) than that in the control group (0.593 ± 0.030). The best risk factor was the LFCR with a cut-off of 0.602 (AUC, 0.818; 95% CI, 0.748–0.878; sensitivity, 90%; specificity, 66%). When combined with lateral tibial slope (cutoff, 7°) and lateral tibial height (cutoff, 3.6 mm), the diagnostic performance was improved significantly (AUC, 0.896; 95% CI, 0.890–0.950; sensitivity, 87%; specificity, 80%).Conclusion:The increased LFCR measured by MRI was associated with a significantly higher risk for ACL injury or rerupture. The combination of LFCR, lateral tibial slope and lateral tibial height were the most predictive risk factors. This may help clinicians identify susceptible individuals and allow precision approaches for better prevention, treatment and management of this disease.

Yunnan snub-nosed monkeys (Rhinopithecus bieti) are the highest elevation lived non-human primate, and their survival has been threatened for decades. To promote their population growth, a reserve provides a typical monkey population with supplemental food. However, the influences of this food provisioning on their gut microbiota and antibiotic resistance genes (ARGs) were unknown. Therefore, we investigated the gut microbiota and ARGs of the food-provisioned monkey population compared with another wild foraging population. We found that food provisioning significantly increased the gut microbiota diversity and changed the community composition, particularly increased both the Firmicutes abundance and Firmicutes/Bacteroidetes ratio. Meanwhile, the food provisioning decreased the complex and stable gut microbiota network. KEGG functions were also influenced by food provisioning, with wild foraging monkeys showing higher functions of metabolism and genetic information processing, especially the carbohydrate metabolism, while food-provisioned monkeys exhibited increased environmental information processing, cellular processes, and organismal systems, including valine, leucine, and isoleucine degradation. In addition, food provisioning increased the abundance of ARGs in the gut microbiota, with most increasing the abundance of bacA gene and changing the correlations between specific ARGs and bacterial phyla in each population. Our study highlights that even food provisioning could promote wildlife nutrient intake, and it is necessary to pay attention to the increased ARGs and potential effects on gut microbiota stability and functions for this human conservation measure.

Morphological control is an effective approach to enhance the rate performance of nanostructured electrode materials, offering a promising solution for alleviating energy concerns. We have utilized a seed-mediated growth method to synthesize hexagonal djurleite (Cu1.94S) nanoplates and nanoflowers under N2 and air, respectively. The influence of the morphology on the ion interaction has been investigated in the storage process through half-cell electrochemical energy storage. Cu1.94S nanoplates performed a higher specific capacity of 193 mAh g−1 at a high rate of 8 A g−1 than nanoflowers and showed excellent cycle stability over 4,000 cycles with capacity retention of 80.8%. The relationship between morphology and electrochemical performance was explored through further electrochemical characterization. It is found that the stacking of hexagonal surfaces of nanoplates increases the contact area of the electrode material and reduced resistance, leading to faster ion migration and a more complete redox process, ultimately contributing to a higher specific capacity. Our study has enhanced the understanding of structure–property relationships for electrode material, providing an insightful approach for the preparation of electrode materials suitable for ultrafast charge and discharge.

Abstract Background Chinese nurses working with immense stress may have issues with burnout during COVID-19 regular prevention and control. There were a few studies investigating status of burnout and associated factors among Chinese nurses. However, the relationships remained unclear. Objectives To investigate status and associated factors of nurses’ burnout during COVID-19 regular prevention and control. Methods 784 nurses completed questionnaires including demographics, Generalized Anxiety Disorder-7, Patient Health Questionnaire-9, Insomnia Severity Index, Impact of Event Scale-revised, Perceived Social Support Scale, Connor–Davidson Resilience Scale, General Self-efficacy Scale and Maslach Burnout Inventory. Results 310 (39.5%), 393 (50.1%) and 576 (73.5%) of respondents were at high risk of emotional exhaustion (EE), depersonalization (DP) and reduced personal accomplishment (PA). The risk of EE, DP and reduced PA were moderate, high and high. Nurses with intermediate and senior professional rank and title and worked >40 h every week had lower scores in EE. Those worked in low-risk department reported lower scores in PA. Anxiety, post-traumatic stress disorder (PTSD), self-efficacy and social support were influencing factors of EE and DP, while social support and resilience were associated factors of PA. Conclusion Chinese nurses’ burnout during COVID-19 regular prevention and control was serious. Professional rank and title, working unit, weekly working hours, anxiety, PTSD, self-efficacy, social support and resilience were associated factors of burnout.

Background Strain analysis is a sensitive method for the assessment of ventricular structural or functional alterations. The authors aimed to determine whether right ventricular (RV) strain parameters can discriminate patients with revised Task Force Criteria–diagnosed arrhythmogenic RV cardiomyopathy (ARVC) incremental to the existing cardiovascular magnetic resonance (CMR) criteria, thus improving the diagnostic yield of CMR in ARVC. Methods and Results A total of 74 patients with revised Task Force Criteria–diagnosed ARVC (37 borderline and 37 definite) and 37 controls were retrospectively enrolled for analysis. Using CMR feature tracking, RV global longitudinal (GLS), circumferential, and radial strain of all participants were evaluated. Compared with controls, the study patients demonstrated significantly impaired global biventricular strain in all 3 directions (all P50% presenting with impaired RV GLS. When both conventional criteria and RV GLS were considered together, this new diagnostic method demonstrated an overall diagnostic accuracy of 90%. The likelihood ratio test showed a significant incremental diagnostic value of RV GLS (P=0.02) over the existing CMR major criteria. Conclusions The current study showed an improved diagnostic accuracy when both RV GLS and the existing CMR criteria were considered together, especially for patients with borderline diagnosis, suggesting the incremental value of strain analysis to the initial assessment of ARVC.

Objective Electroacupuncture (EA) has a definite effect on the treatment of spinal cord injuries (SCIs), but its underlying molecular mechanism remains unclear. Meanwhile, MiR-106b-5p is an autophagy- and apoptosis-related microribonucleic acid, but whether it regulates the progression of autophagy and apoptosis in SCIs is yet undetermined. As such, this study aimed to elucidate the involvement of miR-106b-5p in the EA treatment of an SCI. Methods The miR-106b-5p level was detected by quantitative real-time polymerase chain reaction. In vitro, SH-SY5Y cells were transfected with miR-106b-5p mimics or inhibitors to regulate the miR-106b-5p expression, while in vivo, SCI rats were treated with EA for 7 days at the bilateral Zusanli (ST36) and Jiaji (EX-B2) acupoints. The motor function was evaluated using the Basso-Beattie-Bresnahan (BBB) criteria. Further, autophagic vacuoles, pathological damage, and neuronal cell morphology were observed by transmission electron microscopy, as well as by hematoxylin and eosin and Nissl staining, respectively. Results The miR-106b-5p level, which can interact directly with Beclin-1 by influencing its expression, as well as the expressions of P62, Caspase-3, and Bax, was upregulated after an SCI, but it decreased after EA. Moreover, the ratio of LC3-II to LC3-I was upregulated after EA. EA can enhance autophagy, reduce neuronal apoptosis, and minimize motor dysfunction and histopathological deficits after an SCI. More importantly, however, all the above effects induced by EA can be reversed after an injection of miR-106-5p agomir to produce an overexpression of miR-106b-5p. Conclusion EA treatment could downregulate miR-106b-5p to alleviate SCI-mediated injuries by promoting autophagy and inhibiting apoptosis.

AIM: To investigate the role and mechanism of N6-methyladenosine(m6A)methyltransferase 3(METTL3)in the pathogenesis of diabetic cataract.METHODS: We cultured SRA01/04 cells in low and high sugar media for 24h and measured changes in epithelial-mesenchymal transition(EMT)indicators(E-Cadherin, N-Cadherin, ZO-1 and α-SMA)using RT-qPCR and Western blot assays. Cell migration was also assessed using transwell and scratch assays. To investigate the expression level and localization of METTL3 in human lens anterior capsules tissues. Additionally, we used m6A dot blot assay to detect the m6A methylation level of cells cultured in low and high glucose media for 24h, and employed RT-qPCR and Western blot experiments to detect RNA and protein expression of METTL3 in cells. We then treated the cells with METTL3 inhibitor and measured changes in EMT markers by RT-qPCR and Western blot; m6A methylation level was detected by m6A dot blot test; cell migration was detected by Transwell. Finally, the expression of transforming growth factor-β(TGFβ1)in cultured cells was assessed by immunofluorescence staining and the expression levels of TGFβ1 and SNAIL in cells were determined using RT-qPCR and Western blot.RESULTS: Under high glucose conditions, the expression of EMT markers, METTL3, and m6A methylation levels were significantly increased in cells(P

Objective: The content of starch was closely related to the derivative products of sorghum. It was very important to determination of the content of starch, including amylose (Am) and amylopectin (Ap) in sorghum. In this study, the content of Am and Ap was determined by the iodine colorimetry. And conditions of pretreatment and determination were optimized. Method: Using Am and Ap in sorghum as the main object, the content of starch was measured by the iodine colorimetry with different detection methods, including the single wavelength mixed standard method (I), the dual wavelength single standard method (II), and the dual wavelength mixed standard method (III). A series of methodological verifications, such as the precision, detection limit and quantification limit, were compared. And the conditions of pretreatment, such as NaOH and KOH dispersant, gelatinization temperature and time, acetic acid and hydrochloric acid pH regulator, dosage of iodine reagent and color rendering time were optimized. The repeatability verification recovery rate and the determination of common grain samples of the obtained method was also tested, which verified the accuracy of the method. Result: The detection limits and quantification limits of the three methods could meet the requirements of the actual sample measurement range, with detection limits of Am≤0.55 mg/L, Ap≤2.75 mg/L, quantification limits of Am≤1.65 mg/L, Ap≤8.33 mg/L. The absolute error of the accuracy experiments was 0.13% from the mixed standard solution calibration curve, the single standard solution calibration curve error was relatively large (7.47%), thus the mixed standard solution was better to prepare the calibration curve. The optimal preprocessing of sorghum: Using NaOH as the dispersant, the gelatinization temperature at 70 ℃ for 10~20 min, with acetic acid or hydrochloric acid as pH regulator, using standard iodine reagent concentration, controlling the coloring time at 20~30 min, the determination results were relatively stable and accurate. The total content of starch was consistent with the starch content in theory, and it had a good repeatability and recovery (80%~120%). Conclusion: In summary, the dual wavelength mixed standard method of iodine colorimetry was a best method for measuring the content of Am and Ap in sorghum, and it was more suitable for the determination of actual samples in crops.

Cardiac magnetic resonance (CMR), a non-radiation based type of examination, can achieve the simultaneous comprehensive multi-parameter, multi-plane, and multi-sequence evaluation of the anatomical structure of the heart; and at the same time, determine systolic and diastolic function, and blood perfusion and tissue characteristics. Traditional late gadolinium enhancement imaging based on CMR reflects focal replacement fibrosis, in contrast to normal myocardial signal intensity, but cannot effectively identify diffuse myocardial fibrosis. T1 mapping and its derived extracellular volume fraction can be used to quantitatively analyze the extracellular space in myocardial tissue and evaluate diffuse myocardial interstitial fibrosis that is invisible to the naked eye. Diffusion tensor imaging reveals the direction of cardiomyocyte aggregates by quantifying the anisotropy of water molecule diffusion, and can be applied to evaluate the integrity of myocardial tissue and arrangement structure of myocardial microstructural characteristics. On the basis of the micro-motion of myocardial tissue, feature tracking analysis decomposes myocardial deformation into three dimensions of micro-mechanical changes, and can identify early systolic and diastolic dysfunction before heart enlargement or ejection fraction reduction. This Commentary discusses current research advances in these new techniques, as well as their clinical application prospects and limitations for non-ischemic cardiomyopathies.

To enhance the accuracy of identifying fresh meat varieties using laser-induced breakdown spectroscopy (LIBS), we utilized the LightGBM model in combination with the Optuna algorithm. The procedure involved flattening fresh meat slices with glass slides and collecting spectral data of the plasma from the surfaces of the fresh meat tissues (pork, beef, and chicken) using LIBS technology. A total of 900 spectra were collected. Initially, we established LightGBM and SVM (support vector machine) models for the collected spectra. Subsequently, we applied information gain and peak extraction algorithms to select the features for each model. We then employed Optuna to optimize the hyperparameters of the LightGBM model, while a 10-fold cross-validation was conducted to determine the optimal parameters for SVM. Ultimately, the LightGBM model achieved higher accuracy, macro-F1, and Cohen’s kappa coefficient (kappa coefficient) values of 0.9370, 0.9364, and 0.9244, respectively, compared to the SVM model’s values of 0.8888, 0.8881, and 0.8666. This study provides a novel method for the rapid classification of fresh meat varieties using LIBS.

Abstract Background Herbal medicine Sanqi (SQ), the dried root or stem of Panax notoginseng (PNS), has been reported to have anti-diabetic and anti-obesity effects and is usually administered as a decoction for Chinese medicine. Alternative to utilizing PNS pure compound for treatment, we are motivated to propose an unconventional scheme to investigate the functions of PNS mixture. However, studies providing a detailed overview of the transcriptomics-based signaling network in response to PNS are seldom available. Methods To explore the reasoning of PNS in treating metabolic disorders such as insulin resistance, we implemented a systems biology-based approach with RNA sequencing (RNA-seq) and miRNA sequencing data to elucidate key pathways, genes and miRNAs involved. Results Functional enrichment analysis revealed PNS up-regulating oxidative stress-related pathways and down-regulating insulin and fatty acid metabolism. Superoxide dismutase 1 (SOD1), peroxiredoxin 1 (PRDX1), heme oxygenase-1 (Hmox1) and glutamate cysteine ligase (GCLc) mRNA and protein levels, as well as related miRNA levels, were measured in PNS treated rat pancreatic β cells (INS-1). PNS treatment up-regulated Hmox1, SOD1 and GCLc expression while down-regulating miR-24-3p and miR-139-5p to suppress oxidative stress. Furthermore, we verified the novel interactions between miR-139-5p and miR-24-3p with GCLc and SOD1. Conclusion This work has demonstrated the mechanism of how PNS regulates cellular molecules in metabolic disorders. Therefore, combining omics data with a systems biology strategy could be a practical means to explore the potential function and molecular mechanisms of Chinese herbal medicine in the treatment of metabolic disorders.

AIM: To investigate the role and mechanism of methyltransferase-like 3(METTL3)-mediated N6-methyladenosine(m6A)methylation modification in regulating biological activity of vascular endothelial cells in the pathogenesis of choroidal neovascularization.METHODS: Human umbilical vein endothelial cells(HUVEC)cultured in vitro were divided into the following groups: control group(normal culture), low density lipoprotein(LDL)group, fluorescence-labelled LDL(Dil-LDL)group, 12.5μg/mL and 25μg/mL oxidized LDL(ox-LDL)groups, 12.5μg/mL and 25μg/mL fluorescence-labelled ox-LDL(Dil-ox-LDL)groups, DMSO group, STM2457(METTL3 inhibitor)group, DAPT group; and monkey retina-choroidal endothelial cells(RF/6A)cultured in vitro were divided into control group, DMSO group, 12.5 μg/mL ox-LDL group, and DAPT group. Endocytosed lipoprotein level was examined through fluorescence microscopy. RNA m6A methylation level was detected through a dot blot assay. Protein and RNA levels of METTL3 or angiogenesis-related markers were measured through Western blot assays and real-time quantitative polymerase chain reaction(RT-qPCR), respectively. METTL3 expression and localization were investigated through immunofluorescence. Cell migratory and tube formation capacities were assessed through transwell migration and tube formation assays, respectively.RESULTS: Endocytosed lipoprotein levels in HUVECs exposed to Dil-LDL, 12.5μg/mL and 25μg/mL Dil-ox-LDL groups were significantly higher than those in the control group. 12.5μg/mL and 25μg/mL ox-LDL groups significantly increased m6A methylation(all P0.05). The expression of VEGF and NICD(all P

Ferroptosis is a type of programmed cell death that pathogens can leverage to enhance their replication, transmission, and pathogenicity. Hosts typically combat pathogenic infections by utilizing oxidative stress as a defense mechanism. Nonetheless, some pathogens can trigger considerable oxidative stress while infecting, inducing an intense inflammatory response in the host’s immune system and activating cell death. The process of ferroptosis is closely linked to oxidative stress, with their interaction exerting a substantial impact on the outcome of infectious diseases. This article presents an overview of the interrelated mechanisms of both Ferroptosis and oxidative stress in infectious diseases, identifying potential targets for treating such diseases in the context of their interaction.

AbstractObjective The pathogenesis of renal osteopathy and cardiovascular disease suggests the disordered bone–vessel axis in chronic kidney disease–mineral bone disorder (CKD–MBD). However, the mechanism of the bone–vessel axis in CKD–MBD remains unclear.Methods We established a CKD–MBD rat model to observe the pathophysiological phenotype of the bone–vessel axis and performed RNA sequencing of aortas to identify novel targets of the bone–vessel axis in CKD–MBD.Results The microarchitecture of the femoral trabecular bone deteriorated and alveolar bone loss was aggravated in CKD–MBD rats. The intact parathyroid hormone and alkaline phosphatase levels increased, 1,25-dihydroxyvitamin D3 levels decreased, and intact fibroblast growth factor-23 levels did not increase in CKD–MBD rats at 16 weeks; other bone metabolic parameters in the serum demonstrated dynamic characteristics. With calcium deposition in the abdominal aortas of CKD–MBD rats, RNA sequencing of the aortas revealed a significant decrease in inositol 1,4,5-trisphosphate receptor type 2 (ITPR2) gene levels in CKD–MBD rats. A similar trend was observed in rat aortic smooth muscle cells. As a secretory protein, ITPR2 serum levels decreased at 4 weeks and slightly increased without statistical differences at 16 weeks in CKD–MBD rats. ITPR2 serum levels were significantly increased in patients with vascular calcification, negatively correlated with blood urea nitrogen levels, and positively correlated with serum tartrate-resistant acid phosphatase 5b levels.Conclusion These findings provide preliminary insights into the role of ITPR2 in the bone–vessel axis in CKD–MBD. Thus, ITPR2 may be a potential target of the bone–vessel axis in CKD–MBD.

We evaluated clinical implication of neutrophil-lymphocyte ratio (NLR) for severe heatstroke and predictive value of combined acute physiology and chronic health evaluation (APACHEII) score for prognosis of severe heatstroke. Retrospectively, we studied 185 individuals that have been admitted at emergency department for severe heatstroke. On the basis of their prognosis, we sorted the patients into two categories, namely non-survival (n = 43) and survival groups (n = 142). The primary outcome was 30-day mortality. A considerably higher NLR was observed among the non-survivors compared to survivors (P

Abstract Chemical mutagenicity is a serious issue that needs to be addressed in early drug discovery. Over a long period of time, medicinal chemists have manually summarized a series of empirical rules for the optimization of chemical mutagenicity. However, given the rising amount of data, it is getting more difficult for medicinal chemists to identify more comprehensive chemical rules behind the biochemical data. Herein, we integrated a large Ames mutagenicity data set with 8576 compounds to derive mutagenicity transformation rules for reversing Ames mutagenicity via matched molecular pairs analysis. A well-trained consensus model with a reasonable applicability domain was constructed, which showed favorable performance in the external validation set with an accuracy of 0.815. The model was used to assess the generalizability and validity of these mutagenicity transformation rules. The results demonstrated that these rules were of great value and could provide inspiration for the structural modifications of compounds with potential mutagenic effects. We also found that the local chemical environment of the attachment points of rules was critical for successful transformation. To facilitate the use of these mutagenicity transformation rules, we integrated them into ADMETopt2 ( http://lmmd.ecust.edu.cn/admetsar2/admetopt2/ ), a free web server for optimization of chemical ADMET properties. The above-mentioned approach would be extended to the optimization of other toxicity endpoints. Graphical Abstract

The current target detection network in deep learning has been widely used in plant growth state detection. However, with the development of deep learning, within the field of plant growth state detection, the performance of the detection network is no longer the primary factor limiting the detection accuracy and model generalization ability. The construction of high-quality and large-scale plant datasets is more significant for the improvement of model detection accuracy and generalization ability. However, traditional methods for building deep learning datasets for plants have a large time span and low efficiency. And it is difficult to construct and expand the dataset for plants with complex growth environments and difficult image acquisition by existing methods. To address this problem, this paper proposes a method for constructing plant datasets based on augmented reality techniques. The method proposed in this paper allows for the rapid and efficient construction of large-scale field datasets that match the actual inspection environment in the lack of data. Meanwhile, this paper proposes an automatic annotation method for datasets in conjunction with the imaging environment in virtual space. In this paper, we experimentally compare the proposed method with the method of expanding the dataset using GAN networks. Using the virtual dataset constructed by the method proposed in this paper as the training set, the trained YOLOv5 model achieves an average accuracy (@0.5:0.95) of 0.71 for the three detection categories on the test set. The detection accuracy of the six mixed datasets constructed using the two data expansion methods on the test set was experimentally tested. The proposed method in this paper improved the accuracy by 2.2%, 3.1%, and 7.0%, respectively. The smaller the percentage of real images, the greater the accuracy improvement. Experiments show that the method proposed in this paper can well solve the problems faced in the field of plant growth state detection, such as the lack of data, and provides a new idea for the production and expansion of datasets in plant detection tasks.

With advances in force fields and algorithms, robust tools have been developed for molecular simulation of three-dimensional structures of nucleic acids and investigation of aptamer-target interactions. The traditional aptamer discovery technique, Systematic Evolution of Ligands by EXponential enrichment (SELEX), continues to suffer from high investment and low return, while in vitro screening by simulated SELEX remains a challenging task, where more accurate structural modeling and enhanced sampling limit the large-scale application of the method. Here, we proposed a modified aptamer enhanced library design strategy to facilitate the screening of target-binding aptamers. In this strategy, a comprehensive analysis of the original complexes and the target secondary structure were used to construct an enhanced initial library for screening. Our enhanced sequence library design strategy based on the target secondary structure explored a certain sequence space while ensuring the accuracy of the structural conformation and the calculation method. In an enhanced library of only a few dozen sequences, four sequences showed a similar or better binding free energy than the original aptamer, with consistently high binding stability over three rounds of multi-timescale simulations, ranging from − 30.27 to − 32.25 kcal/mol. Consequently, the enhanced library strategy based on the target secondary structure is shown to have very significant potential as a new aptamer design and optimization strategy.

Abstract Background Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes and causes of blindness in developed countries. Our study was designed to identify immune-related genes involved in the progression of proliferative diabetic retinopathy (PDR). Methods The “GSE102485” dataset of neovascular membrane samples (NVMs) from type 1 and 2 diabetes mellitus patients was downloaded from the Gene Expression Omnibus database. Functional enrichment analyses, protein–protein interaction network (PPI) construction, and module analysis of immune pathways in NVMs and controls were conducted via Gene Set Enrichment Analysis and Metascape. Results The significantly upregulated hallmark gene sets in DR2 and DR1 groups were involved in five immune pathways. Only CCR4, CXCR6, C3AR1, LPAR1, C5AR1, and P2RY14 were not previously reported in the context of PDR molecular pathophysiology. Except for P2RY14, all of the above were upregulated in retinal samples from experimental diabetes mouse models and human retina microvascular endothelial cells (HRMECs) treated with high glucose (HG) by quantitative Real Time Polymerase Chain Reaction (qRT-PCR). Conclusion The genes identified herein provide insight into immune-related differential gene expression during DR progression.

Summary: The impact of climate change on economic inequality has attracted increasing attention from both government and academia. Here, we present a protocol for estimating both the impact of climate change on economic growth and economic growth inequality under multiple climate policies. We describe steps for constructing an uncertainty analysis framework, collecting and pre-processing data, and estimating the climate-economic response. We then detail procedures of predicting climate policy impact and calculating inter-country economic growth inequality.For complete details on the use and execution of this protocol, please refer to Tang et al. (2023).1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Background: Remimazolam besylate is a novel ultra-short-acting benzodiazepine that can potentially be a safe and effective sedative in intensive care units. This study aims to assess whether remimazolam besylate is not inferior to propofol in maintaining mild-to-moderate sedation in critically ill patients receiving long-term mechanical ventilation.Methods and analysis: This is a multicenter, randomized, single-blind, propofol-controlled, non-inferiority study. Eligible patients are randomly assigned to receive remimazolam besylate or propofol in a 1:1 ratio to maintain a Richmond Agitation–Sedation Scale score between −3 and 0. When patients are under-sedated, rescue sedation of dexmedetomidine is added. The primary outcome is the percentage of time in the target sedation range. The secondary outcomes are hours free from the invasive ventilator in 7 days, successful extubation in 7 days, and weaning time, the length of intensive care unit stay, the length of hospital stay, and mortality in 28 days. Modified intention-to-treat and safety analysis is performed.Clinical trial registration number:https://clinicaltrials.gov/ct2/show/NCT05555667.

In order to investigate the influence of particle size on the flotation behavior of coal slime, industrial analysis, elementary analysis, and particle size composition analysis were carried out on coal slime. The coal slime is divided into three sizes: −0.5 + 0.25, −0.25 + 0.074, and −0.074 mm, and full −0.5 mm particle sizes. Through contact angle measurement, wetting heat measurement, and step-by-step release test to investigate the hydrophobicity of each particle size; in addition, the flotation kinetics test of different particle sizes coal slime was also carried out. The results show that the particle size has a significant effect on the flotation behavior of fine coal slime. The medium particle size −0.25 + 0.074 mm has the best hydrophobicity, followed by −0.5 + 0.25 mm, again −0.5 mm, and finally −0.074 mm particle sizes. Use Origin software to fit six kinetic models to the test data of coal slime flotation kinetics, and analyze the maximum combustible recovery r ∞ , flotation rate constant (k), and correlation coefficient ( R 2 ) of each particle size, The results show that the first-order model with rectangular distribution of floatabilities can better describe the flotation of coal slime of each particle size.

Abstract Background As known, inhibition of phosphodiesterase 5 (PDE5) has the therapeutic effect on male erectile dysfunction (ED), and the processed folium of Epimedium sagittatum Maxim. (PFES) characterized by 8-isopentenyl flavonoids is a famous herb for treating ED. However, the main flavonoids inhibitory activities, structure–activity relationship (SAR) and signaling pathway have been not systematically studied so that its pharmacodynamic mechanism is unclear. Methods We aimed to initially reveal the PFES efficacy mechanism for treating ED. For the first time, 6 main 8-isopentenyl flavonoids (1–6) from PFES were isolated and identified. Then based on HPLC detection, we proposed a novel method to screen inhibitors among them. We further analyze the three-dimensional quantitative structure–activity relationship (3D-QSAR) for those inhibitors. Results The results were verified by cellular effects of the screened flavonoids. Among 6 compounds, Icariin: (1), 2-Oʹʹrhamnosylicaridide II (2) and Baohuoside I (3) were identified with significant activities (IC50 = 8.275, 3.233, 5.473 μM). Then 3D-QSAR studies showed that the replacement of C8 with bulky steric groups as isopentenyl, C3 with positive charge groups and C4' with a hydrogen bond acceptor substituent could increase inhibitory effects. In contrast, the substitution of C7 with bulky steric groups or hydrophilic groups tended to decrease the efficacies. And compounds 1, 2, 3 could increase cGMP level and decrease cytoplasmic Ca2+ of rat corpus cavernosum smooth muscle cells (CCSMCs)by activating PKG. Conclusion 8-isopentenyl flavonoids could be the main pharmacodynamic substances of PFES in the treatment for ED, and some had significant PDE5A1 inhibitory activities so as to activate cGMP/PKG/Ca2+ signaling pathway in CCSMCs, that was related to the substituents at the key sites such as C8, C3, C4ʹ and C7 in the characteristic compounds.

Abstract Myopia is a leading cause of visual impairment in young people worldwide. It sometimes increases the risk of blindness and reduces life quality. Previous reports have revealed the treatment effects of defocus-incorporated multiple segments (DIMS) and topical atropine (ATP) on myopia control. However, no study has evaluated these two interventions together. In this retrospective study, we aimed to determine whether the combination of DIMS lenses and 0.01% ATP can slow the progression of myopia compared with DIMS lenses or single vision (SV) lenses alone. We included 107 children with myopia who were treated with DIMS and 0.01% ATP combination (DIMS + ATP group), DIMS monotherapy (DIMS group), or a control group (SV group). We compared treatment effects among three groups in axial length and myopia progression. After a 1-year follow-up, the DIMS + ATP group showed a smaller change in axial length and myopia progression than the DIMS and SV groups (P

Chronic kidney disease (CKD) has recently become a serious health and social concern. Vascular calcification, a common complication of CKD, is a risk factor that increases the incidence and mortality of cardiovascular events in patients with CKD. However, there are currently no effective therapeutic targets that can facilitate treatment with fewer side effects for vascular calcification in CKD. To identify potential therapeutic targets, we performed label-free quantification (LFQ) analyses of protein samples from rat aortic vascular smooth muscle cells (RASMCs) after high-phosphorus treatment by nano-UPLC–MS/MS. We determined that ubiquitin-specific protease 47 (USP47) may be associated with CKD vascular calcification by regulating the osteogenic transdifferentiation of the vascular smooth muscle cell (VSMC) phenotype, thus suggesting a novel and potentially effective therapeutic target for CKD vascular calcification. USP47 knockdown significantly reduced the expression of β-transducin repeat-containing protein (BTRC), serine/threonine-protein kinase akt-1 (AKT1), Klotho, fibroblast growth factor (FGF23), and matrix Gla protein (MGP) in RASMCs after high-phosphorus treatment. Consistent with the results of protein–protein interaction (PPI) analyses, USP47 may be involved in regulating osteogenic transdifferentiation markers, such as runt-related transcription factor 2 (RUNX2), Klotho, FGF23, and MGP through the BTRC/AKT1 pathway upon CKD vascular calcification. These data indicate that USP47 may be associated with vascular calcification in CKD by regulating osteogenic differentiation of VSMCs. USP47 may regulate osteogenic transdifferentiation in VSMCs upon CKD vascular calcification through a process involving the BTRC/AKT1 pathway. This study identified a novel potential therapeutic target for the treatment of vascular calcification in CKD.

Vascular calcification is prominent in patients with chronic kidney disease (CKD) and is a strong predictor of cardiovascular mortality in the CKD population. However, the mechanism underlying CKD-associated vascular calcification remains unclear. To identify potential therapeutic targets, a 5/6 nephrectomy rat model was established by feeding of a high-phosphorous diet as the CKD group and compared with sham group rats at 4 and 16 weeks. Sequencing analyses of the rat aorta revealed 643 upregulated and 1023 downregulated genes at 4 weeks, as well as 899 upregulated and 1185 downregulated genes at 16 weeks in the CKD group compared to the sham group. Bioinformatics analyses suggested that SOST (which encodes sclerostin) and Wnt signaling are involved in CKD-associated vascular calcification. Furthermore, protein-protein interactions analysis revealed interactions between SOST, WNT5A, and WNT5B, that involved runt-related transcription factor 2 (RUNX2) and transgelin (TAGLN). SOST was increased in CKD-associated vascular calcification following reduction of the Wnt signaling, including WNT5A and WNT5B, both in vivo and in vitro. TargetScan was used to predict the microRNAs (miRNAs) targeting WNT5A and WNT5B. The expression levels of miR-542-3p, miR-298-3p, miR-376b-5p, and miR-3568 were significantly reduced, whereas that of miR-742-3p was significantly increased in calcified rat aortic vascular smooth muscle cells (VSMCs). In CKD rat aortas, the expression of miR-542-3p, miR-298-3p, miR-376b-5p, miR-3568, miR-742-3p, and miR-22-5p were significantly reduced at both 4 and 16 weeks. Altogether, owing to several assessments, potentially diagnostic and prognostic biomarkers for improving common CKD diagnostic tools were identified in this study. Abbreviations: BUN: blood urea nitrogen; CKD: chronic kidney disease; CKD-MBD: chronic kidney disease-mineral bone disorder; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GO: the Gene Ontology; HE: hematoxylin-eosin; HRP: horseradish peroxidase; KEGG: Kyoto Encyclopedia of Genes and Genomes; MiRNAs: microRNAs; PAS: periodic acid-Schiff; RUNX2: runt-related transcription factor 2; SCr: serum creatinine; STRING: the Search Tool for the Retrieval of Interacting Genes/Proteins; TAGLN: transgelin; VSMC: vascular smooth muscle cell.

Urban Agglomeration (UA) is regarded as an emerging complex urban system in China. The development of UA demands a reasonable scale structure, which can be investigated by Zipf’s law. However, few studies have been conducted to quantify the optimal scale of UA and how its development deviates from the optimal scale. With the continuous urban expansion, the problem of UAs’ scale structure has received increasing attention. In this study, we propose a method based on Zipf’s law for estimating the theoretical optimal scale of UAs in China and assessing the deviation rate from their optimal scales. Twelve typical UAs in China are selected, and their development is assessed via urban impervious surface data from 2000 to 2018. The results show that the average deviation rate of the investigated UAs decreased from 3.40% in 2000 to 2.32% in 2018, demonstrating that these UAs are on a positive evolution trajectory. Furthermore, according to the development stage, we make recommendations on “large cities vs. medium/small-sized cities and promoting vs. restraining” to each UA based on its size. The conceptual and analytical knowledge, as well as the results from this study, are expected to offer valuable insights and new references for regulating and managing UAs’ development in China.

Abstract Objective The aim of this study was to evaluate the efficacy and safety of remimazolam besylate compared with propofol in maintaining mild-to-moderate sedation in patients receiving long-term mechanical ventilation. Methods In this single-centered randomized pilot study, adult patients mechanically ventilated longer than 24 h were randomized to receive remimazolam besylate or propofol. The target sedation range was − 3 to 0 on the Richmond Agitation and Sedation Scale (RASS). The primary outcome was the percentage of time in the target sedation range without rescue sedation. The secondary outcomes were ventilator-free days at day 7, the length of ICU stay and 28-day mortality. Results Thirty patients were assigned to each group. No difference was identified between the remimazolam group and propofol group in median age [60.0 (IQR, 51.5–66.3) years vs. 64.0 (IQR, 55.0–69.3) years, respectively, p = 0.437] or the median duration of study drug infusion [55.0 (IQR, 28.3–102.0) hours vs. 41.0 (IQR, 24.8–74.3) hours, respectively, p = 0.255]. The median percentage of time in the target RASS range without rescue sedation was similar in remimazolam and propofol groups [73.2% (IQR, 41.5–97.3%) vs. 82.8% (IQR, 65.6–100%), p = 0.269]. No differences were identified between the two groups in terms of ventilator-free days at day 7, length of ICU stay, 28-day mortality or adverse events. Conclusions This pilot study suggested that remimazolam besylate was effective and safe for long-term sedation in mechanically ventilated patients compared with propofol.

Abstract UDP-glucuronosyltransferases (UGTs) have gained increasing attention as they play important roles in the phase II metabolism of drugs. Due to the time-consuming process and high cost of experimental approaches to identify the metabolic fate of UGT enzymes, in silico methods have been developed to predict the UGT-mediated metabolism of drug-like molecules. We developed consensus models with the combination of machine learning (ML) and graph neural network (GNN) methods to predict if a drug-like molecule is a potential UGT substrate, and then we applied the Weisfeiler-Lehman Network (WLN) model to identify the sites of metabolism (SOMs) of UGT-catalyzed substrates. For the substrate model, the accuracy of the single substrate prediction model on the test set could reach to 0.835. Compared with the single estimators, the consensus models are more stable and have better generalization ability, and the accuracy on the test set reached to 0.851. For the SOM model, the top-1 accuracy of the SOM model on the test set reached to 0.898, outperforming existing works. Thus, in this study, we proposed a computational framework, named Meta-UGT, which would provide a useful tool for the prediction and optimization of metabolic profiles and drug design. Graphical Abstract

Summary: We aimed to investigate the mechanisms of Brahma related gene 1 (BRG1) in promoting vascular calcification in chronic kidney disease (CKD). The expression of BRG1 was examined in high phosphorus stimulated rat aortic smooth muscle cells (RASMCs) and calcified artery tissues from rat models and hemodialysis patients. Autophagosome formation was measured in high phosphorus stimulated RASMCs with and without BRG1 knock-down. We also detected the coexistence of BGR1 and exosomes, and measured the circulatory levels of BRG1 in the hemodialysis patients. BRG1 promoted the osteogenic transdifferentiation of RASMCs. Silencing BRG1 prevented autophagy from being induced by high phosphorus stimulation in RASMCs. Increased expression of BRG1 was observed in calcified blood vessels. Serum BRG1 level increased in the hemodialysis patients. BRG1 was involved in the development of high phosphorus induced osteogenic phenotype in vitro and in vivo, and its underlying mechanism might be facilitating autophagy.