Search

Background The associations between cardiovascular disease (CVD) and multiple psychiatric disorders and suicide attempt, and whether different genetic susceptibilities affect such links, have not been investigated clearly. Methods and Results Based on the UK Biobank, we conducted a matched cohort study involving 63 923 patients who were first hospitalized with a CVD diagnosis between 1997 and 2020, and their 127 845 matched unexposed individuals. Cox models were used to examine the subsequent risk of psychiatric disorders and suicide attempt (ie, anxiety, depression, stress‐related disorder, substance misuse, psychotic disorder, and suicide behaviors) following CVD. We further performed stratified analyses by polygenic risk score for each studied psychiatric condition to detect the possible effects of genetic susceptibility on the observed associations. We found an increased risk of any psychiatric disorders and suicide attempt among CVD patients, compared with matched unexposed individuals, particularly within 1 year following the CVD (fully adjusted hazard ratio [HR] within 1 year, 1.83 [95% CI, 1.58–2.12]; HR after 1 year, 1.24 [95% CI, 1.16–1.32]). By subtype, the risk elevations existed for any psychiatric disorders and suicide attempt following most categories of CVDs. Analyses stratified by polygenic risk score revealed little impact of genetic predisposition to studied psychiatric conditions on these observed links. Conclusions Patients hospitalized for CVD were at increased subsequent risk of multiple types of psychiatric disorders and suicide attempt, especially in the first year after hospitalization, irrespective of their genetic susceptibilities to studied psychiatric conditions, and these findings underscore the necessity of developing timely psychological interventions for this vulnerable population.

AlkB homolog 1 (ALKBH1) is a member of the AlkB family of dioxygenases that are dependent on Fe(II) and α-ketoglutarate. Mounting evidence demonstrates that ALKBH1 exhibits enzymatic activity against various substrates, including N6-methyladenosine (m6A), N1-methyladenosine (m1A), N3-methylcytidine (m3C), 5-methylcytosine (m5C), N6-methyladenine (N6-mA, 6mA), and H2A, indicating its dual roles in different biological processes and involvement in human diseases. Up to the present, there is ongoing debate regarding ALKBH1's enzymatic activity. In this review, we present a comprehensive summary of recent research on ALKBH1, including its substrate diversity and pathological roles in a wide range of human disorders, the underlying mechanisms of its functions, and its dysregulation. We also explored the potential of ALKBH1 as a prognostic target.

Abstract Background Nucleotide-binding oligomerization domain-containing protein 1 (NOD1) plays a pivotal role in inducing metabolic inflammation in diabetes. Additionally, the NOD1 ligand disrupts the equilibrium of bone marrow-derived hematopoietic stem/progenitor cells, a process that has immense significance in the development of diabetic retinopathy (DR). We hypothesized that NOD1 depletion impedes the advancement of DR by resolving bone marrow dysfunction. Methods We generated NOD1−/−-Akita double-mutant mice and chimeric mice with hematopoietic-specific NOD1 depletion to study the role of NOD1 in the bone marrow–retina axis. Results Elevated circulating NOD1 activators were observed in Akita mice after 6 months of diabetes. NOD1 depletion partially restored diabetes-induced structural changes and retinal electrical responses in NOD1−/−-Akita mice. Loss of NOD1 significantly ameliorated the progression of diabetic retinal vascular degeneration, as determined by acellular capillary quantification. The preventive effect of NOD1 depletion on DR is linked to bone marrow phenotype alterations, including a restored HSC pool and a shift in hematopoiesis toward myelopoiesis. We also generated chimeric mice with hematopoietic-specific NOD1 ablation, and the results further indicated that NOD1 had a protective effect against DR. Mechanistically, loss of hematopoietic NOD1 resulted in reduced bone marrow-derived macrophage infiltration and decreased CXCL1 and CXCL2 secretion within the retina, subsequently leading to diminished neutrophil chemoattraction and NETosis. Conclusions The results of our study unveil, for the first time, the critical role of NOD1 as a trigger for a hematopoietic imbalance toward myelopoiesis and local retinal inflammation, culminating in DR progression. Targeting NOD1 in bone marrow may be a potential strategy for the prevention and treatment of DR.

Abstract Anxiety/stress-related disorders have been associated with multiple diseases, whereas a comprehensive assessment of the structure and interplay of subsequent associated diseases and their genetic underpinnings is lacking. Here, we first identify 136, out of 454 tested, medical conditions associated with incident anxiety/stress-related disorders attended in specialized care using a population-based cohort from the nationwide Swedish Patient Register, comprising 70,026 patients with anxiety/stress-related disorders and 1:10 birth year- and sex-matched unaffected individuals. By combining findings from the comorbidity network and disease trajectory analyses, we identify five robust disease clusters to be associated with a prior diagnosis of anxiety/stress-related disorders, featured by predominance of psychiatric disorders, eye diseases, ear diseases, cardiovascular diseases, and skin and genitourinary diseases. These five clusters and their featured diseases are largely validated in the UK Biobank. GWAS analyses based on the UK Biobank identify 3, 33, 40, 4, and 16 significantly independent single nucleotide polymorphisms for the link to the five disease clusters, respectively, which are mapped to several distinct risk genes and biological pathways. These findings motivate further mechanistic explorations and aid early risk assessment for cluster-based disease prevention among patients with newly diagnosed anxiety/stress-related disorders in specialized care.

Background Stroke patients with coexisting intracranial artery stenosis (ICAS) and white matter lesions (WML) usually have a poor outcome. However, how WML affects stroke prognosis has not been determined. Objective To investigate the quantitative forward flow at the middle cerebral artery in ICAS patients with different degrees of WML using 4D flow. Design Single-center cross-sectional cohort study. Methods Ischemic stroke patients with symptomatic middle cerebral artery (MCA) atherosclerosis were included, and they were divided into 2 groups based on Fazekas scale on Flair image (mild group = Fazekas 0-2, and severe group = Fazekas >2), TOF-MRA and 4D flow were performed to quantify the stenosis degree and forward flow at the proximal of stenosis. The flow parameters were compared between different white matter hyperintensity (WMH) groups, as well as in different MCA stenosis groups, logistic regression was used to validate the association between forward flow and WMH. Results A total of 66 patients were included in this study (mean age 56 years old, 68.2% male). 77.3% of them presented with WMH (Fazekas 1-5). Comparison of flow index between mild and severe WMH groups found a significantly lower forward flow (2.34 ± 1.09 vs 3.04 ± 1.35), higher PI (0.75 ± 0.43 vs 0.66 ± 0.32), and RI (0.49 ± 0.19 vs 0.46 ± 0.15) at ipsilateral infarction MCA in the severe WMH group, all P -values

BackgroundOxidative Balance Score (OBS) is a tool for assessing the oxidative stress-related exposures of diet and lifestyle. The study aimed to investigate the association between OBS and low muscle mass.MethodsOverall, 6,307 individuals over the age of 18 were assessed using data from the 2011 to 2018 National Health and Nutrition Examination Survey (NHANES). Weighted logistic regression and models were used, together with adjusted models.ResultsThere was a negative relationship between OBS and low muscle mass [odds ratio (OR): 0.96, 95% confidence interval (CI): 0.94–0.97, p< 0.0001] using the first OBS level as reference. The values (all 95% CI) were 0.745 (0.527–1.054) for the second level, 0.650 (0.456–0.927) for the third level, and 0.326 (0.206–0.514) for the fourth level (P for trend

Abstract Paternal abuse of drugs, such as methamphetamine (METH), elevates the risk of developing addiction in subsequent generations, however, its underlying molecular mechanism remains poorly understood. Male adult mice (F0) were exposed to METH for 30 days, followed by mating with naïve female mice to create the first-generation mice (F1). When growing to adulthood, F1 were subjected to conditioned place preference (CPP) test. Subthreshold dose of METH (sd-METH), insufficient to induce CPP normally, were used in F1. Selective antagonist (betaxolol) for β1-adrenergic receptor (ADRB1) or its knocking-down virus were administrated into mPFC to regulate ADRB1 function and expression on CaMKII-positive neurons. METH-sired male F1 acquired sd-METH-induced CPP, indicating that paternal METH exposure induce higher sensitivity to METH in male F1. Compared with saline (SAL)-sired male F1, CaMKII-positive neuronal activity was normal without sd-METH, but strongly evoked after sd-METH treatment in METH-sired male F1 during adulthood. METH-sired male F1 had higher ADRB1 levels without sd-METH, which was kept at higher levels after sd-METH treatment in mPFC. Either inhibiting ADRB1 function with betaxolol, or knocking-down ADRB1 level on CaMKII-positive neurons (ADRB1CaMKII) with virus transfection efficiently suppressed sd-METH -evoked mPFC activation, and ultimately blocked sd-METH-induced CPP in METH-sired male F1. In the process, the p-ERK1/2 and ΔFosB may be potential subsequent signals of mPFC ADRB1CaMKII. The mPFC ADRB1CaMKII mediates paternal METH exposure-induced higher sensitivity to drug addiction in male offspring, raising a promising pharmacological target for predicting or treating transgenerational addiction.

This paper explores how the combination of artificial intelligence, simulation, and e-collaborative (AISEC) tools can support accessibility in analytics courses within higher education. In the era of online and blended learning, addressing the diverse needs of students with varying linguistic backgrounds and analytical proficiencies poses a significant challenge. This paper discusses how the combination of AISEC tools can contribute to mitigating barriers to accessibility for students undertaking analytics courses. Through a comprehensive review of existing literature and empirical insights from practical implementations, this paper shows the synergistic benefits of using AISEC tools for facilitating interactive engagement in analytics courses. Furthermore, the manuscript outlines practical strategies and best practices derived from real-world experiences carried out in different universities in Spain, Ireland, and Portugal.

The integration of medical imaging and artificial intelligence (AI) has revolutionized interventional therapy of valvular heart diseases (VHD), owing to rapid development in multimodality imaging and healthcare big data. Medical imaging techniques, such as echocardiography, cardiovascular magnetic resonance (CMR) and computed tomography (CT), play an irreplaceable role in the whole process of pre-, intra- and post-procedural intervention of VHD. Different imaging techniques have unique advantages in different stages of interventional therapy. Therefore, single imaging technique can’t fully meet the requirements of complicated clinical scenarios. More importantly, a single intraoperative image provides only limited vision of the surgical field, which could be a potential source for unsatisfactory prognosis. Besides, the non-negligible inter- and intra-observer variability limits the precise quantification of heart valve structure and function in daily clinical practice. With the help of analysis clustered and regressed by big data and exponential growth in computing power, AI broken grounds in the interventional therapy of VHD, including preoperative planning, intraoperative navigation, and postoperative follow-up. This article reviews the state-of-the-art progress and directions in the application of AI for medical imaging in the interventional therapy of VHD.

Abstract Background Metabolic dysfunction associated with fatty liver disease (MAFLD) is often correlated with obesity and hyperuricemia. The present study aimed to determine the association between serum uric acid (SUA) and central fat distribution in patients with MAFLD. Methods A total of 485 patients were classified into the following groups: (1) controls without MAFLD and hyperuricemia (HUA), (2) MAFLD with normal SUA, and (3) MAFLD with HUA. DUALSCAN HDS-2000 was used to measure visceral fat (VAT) and subcutaneous fat (SAT). Dual-energy X-ray absorptiometry (DEXA) was used to measure body fat distribution. Results MAFLD patients with HUA had remarkably higher BMI, fasting insulin, OGIRT AUC, ALT, AST, TG, VAT, SAT, Adipo-IR, trunk fat mass, android fat, and total body fat than MAFLD patients with normal SUA (all p

Abstract Background Distant metastasis is the main cause of mortality in colorectal cancer (CRC) patients. N1‐methyladenosine (m1A) is a type of epitranscriptome modification. While its regulatory effect on mRNA and its role in CRC metastasis remain unclear. Methods The m1A methylation profile of mRNAs in CRC was revealed by m1A methylated RNA immunoprecipitation sequencing. The expression of MFAP2 in tumor tissues was measured by immunohistochemistry and then correlated with the clinical characteristics and prognosis of CRC patients. The role of MFAP2 in the invasiveness of CRC cells was evaluated by transwell assays and peritoneal metastatic model in nude mice. The downstream targets of MFAP2 was screened by mass spectrometry analysis. Then the role of MFAP2‐CLK3 signaling axis was verified by cotransfecting MFAP2 siRNA and CLK3 plasmid in CRC cells. Results Microfibril associated protein 2 (MFAP2) mRNA was overexpressed and m1A‐hypermethylated in CRC. High expression of MFAP2 was closely related to lymph node metastasis and distant metastasis, leading to poor prognosis in patients with CRC. In vivo and in vitro studies showed that silencing of MFAP2 inhibited the migration, invasion and metastasis of CRC cells. CDC Like Kinase 3 (CLK3) was a potential downstream target of MFAP2. Further studies showed that MFAP2 depletion might induce autophagic degradation of CLK3, and the role of MFAP2 in the invasiveness of CRC cells was dependent on CLK3. Conclusions Our results uncover a newly identified MFAP2‐CLK3 signaling axis, which is a potential therapeutic target for CRC metastasis.

The approach combining ultra-high performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS) for determining hyaluronic acid in dairy products was proposed in this study. The samples were degraded by hyaluronidase, diluted with acetonitrile, and then purified by PRIME HLB cartridge. The analysis was conducted on a BEH Amide column (2.1 mm×100 mm, 1.7 μm) by gradient elution using 0.2% concentration of aqueous ammonia solution and acetonitrile (containing 0.2% ammonia) as mobile phases. Qualification was achieved by negative electrospray ionization with multiple reaction monitoring (MRM). Meanwhile, the external standard method for quantitation was applied. In accordance with the results, the recoveries of hyaluronic acid in dairy products were 91.4%~106.2%, and RSDs were 2.3%~6.7% at the addition levels of 0.5~200 mg/kg. Presumably, with a limit of quantification of 0.5 mg/kg, the demonstrated method was easy and feasible for quantifying the hyaluronic acid in dairy products. This method was used to detect commercially dairy products, and the tested samples meet the standard requirements.

Garden waste, one type of lignocellulosic biomass, holds significant potential for the production of volatile fatty acids (VFAs) through anaerobic fermentation. However, the hydrolysis efficiency of garden waste is limited by the inherent recalcitrance, which further influences VFA production. Granular activated carbon (GAC) could promote hydrolysis and acidogenesis efficiency during anaerobic fermentation. This study developed a strategy to use GAC to enhance the anaerobic fermentation of garden waste without any complex pretreatments and extra enzymes. The results showed that GAC addition could improve VFA production, especially acetate, and reach the maximum total VFA yield of 191.55 mg/g VSadded, which increased by 27.35% compared to the control group. The highest VFA/sCOD value of 70.01% was attained in the GAC-amended group, whereas the control group only reached 49.35%, indicating a better hydrolysis and acidogenesis capacity attributed to the addition of GAC. Microbial community results revealed that GAC addition promoted the enrichment of Caproiciproducens and Clostridium, which are crucial for anaerobic VFA production. In addition, only the GAC-amended group showed the presence of Sphaerochaeta and Oscillibacter genera, which are associated with electron transfer processes. Metagenomics analysis indicated that GAC addition improved the abundance of glycoside hydrolases (GHs) and key functional enzymes related to hydrolysis and acidogenesis. Furthermore, the assessment of major genera influencing functional genes in both groups indicated that Sphaerochaeta, Clostridium, and Caproicibacter were the primary contributors to upregulated genes. These findings underscored the significance of employing GAC to enhance the anaerobic fermentation of garden waste, offering a promising approach for sustainable biomass conversion and VFA production.

Abstract Background The study aims to investigate the relationship between the volume-accumulated reflectivity (termed “integral”) on spectral domain optical coherence tomography (SD-OCT) and cone density on adaptive optics (AO) imaging. Methods In this cross-sectional study, both eyes of 32 healthy subjects and 5 patients with inherited retinal diseases (IRD) were studied. The parameter, integral, was defined as the volume-accumulated reflectivity values in a selected region on OCT images; integrals of the ellipsoid zone (EZ) and interdigitation zone (IZ) were measured at 2°, 3°, 4°, 5°and 6° eccentricity along the four meridians on fovea-centered OCT B-scans. Cone density in the same region was measured using a flood illumination adaptive optics camera RTX1. Results Integrals of EZ, IZ and cone density shared similar distribution patterns. Integral of the IZ was better correlated with cone density in both healthy people (r = 0.968, p

Colorectal cancer (CRC) is one of the most common malignancies, and the main cause of death from CRC is tumor metastasis. m1A RNA modification plays critical role in many biological processes. However, the role of m1A modification in CRC remains unclear. Here, we find that the m1A demethylase alkB homolog 1, histone H2A dioxygenase (ALKBH1) is overexpressed in CRC and is associated with metastasis and poor prognosis. Upregulation of ALKBH1 expression promotes CRC metastasis in vitro and in vivo. Mechanistically, knockdown of ALKBH1 results in a decrease in methyltransferase 3, N6‐adenosine‐methyltransferase complex catalytic subunit (METTL3) expression, probably due to m1A modification of METTL3 mRNA, followed by m6A demethylation of SMAD family member 7 (SMAD7) mRNA. In addition, downregulation of SMAD7 establishes an aggressive phenotype. More importantly, the cell migration and invasion defects caused by ALKBH1 depletion or METTL3 depletion are significantly reversed by SMAD7 silencing. Considering these results collectively, we propose that ALKBH1 promotes CRC metastasis by destabilizing SMAD7 through METTL3.

Abstract Vascular endothelial barrier dysfunction is the most prominent manifestation and important cause of mortality in infectious acute lung injury (ALI). Exogenous apelin is effective in ameliorating lipopolysaccharide (LPS)-induced inflammatory response in ALI lungs, reducing exudation of lung tissue and decreasing mortality. This study set out to investigate the association between apelin and Friend leukemia integration-1 (Fli-1) in the prevention and treatment of ALI, and to elucidate the molecular mechanism by which apelin protects the permeability of the vascular endothelial barrier. At the vivo functional level, lung wet/dry weight ratio was used to detect whole lung permeability, evans blue assay and dual fluorescent protein tracking assay were used to detect lung vascular endothelial permeability, HE staining to observe the inflammatory status of lung tissue, and immunofluorescence staining for VE-cadherin expression levels in blood vessels. The changes in inflammatory factors in bronchoalveolar lavage fluid (BALF) were detected by ELASA. Western blot was used to detect the expression level of proteins. qRT-PCR was performed to detect changes in mRNA expression of Fli-1 and adherent junction-related proteins. The correlation analysis of Fli-1 with vascular endothelial permeability and SRC showed that Fli-1 participated in the process of ALI. After preventive and therapeutic treatment of ALI mice with exogenous apelin, Fli-1, APJ, VE-cadherin, phosphorylated-VE-cadherin (p-VE-cadherin) and β-catenin were up-regulated, while SRC, phosphorylated-SRC (p-SRC), VEGF and VEGF-R were down-regulated, which indicated that the stability of vascular endothelial barrier was enhanced. With the use of Fli-1 inhibitor irinotecan, the protective effect of apelin was weakened in various functional indexes, genes and proteins. The lung was maintained at the level of the injury. Our research shows that Fli-1 is involved in the LPS-induced ALI process. The molecular mechanism for apelin in preventing endothelial barrier dysfunction in ALI is through up-regulating Fli-1, thus regulating adherens junction-related proteins, and finally recovering the endothelial barrier function.

BackgroundA model to predict preoperative outcomes after percutaneous nephrolithotomy (PCNL) with renal staghorn stones is developed to be an essential preoperative consultation tool.ObjectiveIn this study, we constructed a predictive model for one-time stone clearance after PCNL for renal staghorn calculi, so as to predict the stone clearance rate of patients in one operation, and provide a reference direction for patients and clinicians.MethodsAccording to the 175 patients with renal staghorn stones undergoing PCNL at two centers, preoperative/postoperative variables were collected. After identifying characteristic variables using PCA analysis to avoid overfitting. A predictive model was developed for preoperative outcomes after PCNL in patients with renal staghorn stones. In addition, we repeatedly cross-validated their model’s predictive efficacy and clinical application using data from two different centers.ResultsThe study included 175 patients from two centers treated with PCNL. We used a training set and an external validation set. Radionics characteristics, deep migration learning, clinical characteristics, and DTL+Rad-signature were successfully constructed using machine learning based on patients’ pre/postoperative imaging characteristics and clinical variables using minimum absolute shrinkage and selection operator algorithms. In this study, DTL-Rad signal was found to be the outstanding predictor of stone clearance in patients with renal deer antler-like stones treated by PCNL. The DTL+Rad signature showed good discriminatory ability in both the training and external validation groups with AUC values of 0.871 (95% CI, 0.800-0.942) and 0.744 (95% CI, 0.617-0.871). The decision curve demonstrated the radiographic model’s clinical utility and illustrated specificities of 0.935 and 0.806, respectively.ConclusionWe found a prediction model combining imaging characteristics, neural networks, and clinical characteristics can be used as an effective preoperative prediction method.

2D III-VI semiconductors have emerged as promising materials for optoelectronic devices due to their tunable bandgaps, efficient light absorption and high carrier mobility. Among III-VI group, 2D indium telluride (InTe) has been studied very little compared with its well-known congeners such as InSe and GaSe. Although InTe possesses remarkable electrical and optical properties, the investigation of its device applications is greatly hindered due to the shortage of scalable synthesis method. Here, we synthesized centimeter-scale 2D InTe films via a pulsed laser deposition method. The structure of as-grown InTe films was systematically studied, exhibiting good continuity, uniformity and high degree of crystallinity. Meanwhile, layer-dependent bandgaps (1.21∼1.65 eV) were observed from the optical characterization. The InTe based photodetectors show a broadband photoresponse from ultraviolet (370 nm) to near-infrared region (980 nm). The photoresponsivity and detectivity of the InTe photodetectors can achieve 6.35 A/W and 1.55×1011 under 370 nm illumination, respectively, which outperform many photodetectors based on large-area 2D materials. Notably, InTe photodetectors also demonstrate strong layer-dependent photoresponse from 2 L to 10 L upon different wavelength illumination. Our work will inspire the research interests to further develop the practical applications of 2D InTe in the field of photodetection devices.

Perovskite oxide heterostructures exhibit a series of correlated electronic functionalities, associated with the coupling among the lattice, charge, spin and orbital orderings. As a fundamental thermodynamic parameter, temperature measurement is critical to both fundamental research and practical devices. To date, most of temperature sensing for heterostructures are based on electrical resistance-based thermometry. However, they are sensitive to environmental conditions as well as electromagnetic interference, and are impractical in harsh environments or close systems due to the direct contact operation mode. Contactless optical thermometry based on lanthanide luminescence appears as a promising alternative technique, and aims to bypass abovementioned limitations. Herein, we propose a reliable fluorescence intensity ratio-type optical thermometer based on the thermally coupled energy levels of Er3+, which allows remote probing the temperature variation in a series of perovskite heterostructures. Especially, the proposed optical thermometry also enables in-situ characterization of phase transition occurred in the perovskite heterostructures. Our work demonstrates the great potential of optical thermometry in the exploration of thermal phenomena in perovskite oxide heterostructures.

Abstract The Bower's Berylmys (Berylmys bowersi) is one of the largest rodent species with a wide distribution range in southern China and the Indochinese Peninsula. The taxonomy and evolutionary history of the B. bowersi is still controversial and confusing. In this study, we used two mitochondrial (Cyt b and COI) and three nuclear (GHR, IRBP, and RAG1) genes to estimate the phylogeny, divergence times, and biogeographic history of B. bowersi. We also explored morphological variations among the specimens collected across China. Our phylogenetic analyses indicated that the traditional B. bowersi contains at least two species: B. bowersi and B. latouchei. Berylmys latouchei was considered a junior synonym of B. bowersi distributed in eastern China, which is confirmed to be distinguishable at specific level because of its larger size, relatively larger and whiter hind feet, and several cranial traits. The estimated split of B. bowersi and B. latouchei was at the early Pleistocene (ca. 2.00 Mya), which might be the outcome of the combined effects of climate change in the early Pleistocene and isolation by the Minjiang River. Our results highlight the Wuyi Mountains in northern Fujian, China, as a glacial refugia during the Pleistocene and call for more intensive surveys and systematic revisions of small mammals in eastern China.

Abstract Background More information about the impacts of comprehensive pharmaceutical care program (CPCP) on the identification and resolution of drug-related problems (DRPs) is needed. This study aimed at researching the characteristics of DRPs in osteoporosis patients and evaluating the effect of CPCP in identifying and addressing DRPs. Methods We performed a prospective interventional study in a teaching hospital. CPCP was established and conducted to identify and resolve DRPs by a multidisciplinary team (MDT) based on the Pharmaceutical Care Network Europe (PCNE) classification V9.0. Six pharmacists and one doctor worked directly in the study. All data was obtained from electronic medical records, direct observation and visits. The statistical analyses were performed using the SPSS Statistics software version 26.0. Results Two hundred nineteen patients with osteoporosis were included in the final analysis. A total of 343 DRPs were identified, with an average of 1.57 DRPs per patient. The most common DRPs identified were “treatment safety P2” (66.8%; 229/343), followed by “other P3” (21.0%; 72/343) and “treatment effectiveness, P1” (12.2%; 42/343). The primary causes of DRPs were “dose selection C3” (35.9%; 211/588), followed by “drug use process C6” (28.9%; 170/588) and “drug selection C1” (12.6%; 74/588). Seven hundred eleven interventions were proposed to address the 343 DRPs, with an average of 2.1 interventions per DRP. The acceptance rate reached 95.9, and 91.0% of these accepted interventions were fully implemented. As a result, only 30 DRPs were unsolved before discharge. Additionally, the number of drugs was found to be associated with the number of DRPs significantly (p = 0.023). Conclusion DRPs frequently occurred in hospitalized osteoporosis patients. CPCP could be an effect option to solve and reduce DRPs for osteoporosis patients and should be implemented widely to increase patient safety.

Abstract Background Emerging evidence have revealed that circRNAs exert important biological effects in the development and progression of various diseases, including cancer. Our study aimed to elaborated the biological effects of hsa-circ_0003570 in hepatocellular carcinoma (HCC) development at the molecular level. Results The results of functional experiments showed that knockdown of circ_0003570 induced HCC cell growth, migration and invasion, whereas overexpression of circ_0003570 presented the opposite effects. In vivo experiments, xenograft tumors grown from circ-overexpressed cells had smaller tumor volume and weight than the control group. Further investigations suggested that circ_0003570 may function as a competing endogenous RNA via competitively binding miR-182-5p and thereby regulating the repression of downstream target gene STARD13, which were demonstrated by dual luciferase reporter assay and functional rescued experiments. Conclusions Taken together, circ_0003570 suppresses the development of HCC by modulating miR-182-5p/STARD13 axis.

The emotion recognition of medium audio/video in affective computing has important application value for deep cognition in human-computer interaction (HCI)/brain-computer interaction (BCI) and other fields. Especially in the modern distance education, music emotion analysis can be used as one of the important techniques for real-time evaluation of teaching process. In complex dance scenes, the accuracy of music emotion analysis with traditional methods is not high. Therefore, this paper proposes a novel long short-term memory (LSTM) network model for multimodal music emotion analysis in affective computing. Dual-channel LSTM is used to simulate human auditory and visual processing pathways respectively to process the emotional information of music and facial expressions. Then, we train and test the model on an open bi-modal music dataset. Based on the LSTM model, the analytic hierarchy process (AHP) is introduced to fuse weighted feature at decision level. Finally, experiments show that the proposed method can effectively improve the recognition rate, and save a lot of training time.

Abstract Background Whether a genetic predisposition to psychiatric disorders is associated with coronavirus disease 2019 (COVID-19) is unknown. Methods Our analytic sample consisted of 287,123 white British participants in UK Biobank who were alive on 31 January 2020. We performed a genome-wide association study (GWAS) analysis for each psychiatric disorder (substance misuse, depression, anxiety, psychotic disorder, and stress-related disorders) in a randomly selected half of the study population (“base dataset”). For the other half (“target dataset”), the polygenic risk score (PRS) was calculated as a proxy of individuals’ genetic predisposition to a given psychiatric phenotype using discovered genetic variants from the base dataset. Ascertainment of COVID-19 was based on the Public Health England dataset, inpatient hospital data, or death registers in UK Biobank. COVID-19 cases from hospitalization records or death records were considered “severe cases.” The association between the PRS for psychiatric disorders and COVID-19 risk was examined using logistic regression. We also repeated PRS analyses based on publicly available GWAS summary statistics. Results A total of 143,562 participants (including 10,868 COVID-19 cases) were used for PRS analyses. A higher genetic predisposition to psychiatric disorders was associated with an increased risk of any COVID-19 and severe COVID-19. The adjusted odds ratio (OR) for any COVID-19 was 1.07 (95% confidence interval [CI] 1.02–1.13) and 1.06 (95% CI 1.01–1.11) among individuals with a high genetic risk (above the upper tertile of the PRS) for substance misuse and depression, respectively, compared with individuals with a low genetic risk (below the lower tertile). Slightly higher ORs were noted for severe COVID-19, and similar result patterns were obtained in analyses based on publicly available GWAS summary statistics. Conclusions Our findings suggest a potential role of genetic factors in the observed phenotypic association between psychiatric disorders and COVID-19. Our data underscore the need for increased medical surveillance for this vulnerable population during the COVID-19 pandemic.

Submarine landslides, one of the hotspots in marine geoscience research, are one of the most harmful marine geological disasters. To understand the research status and further research directions of submarine landslides, this paper analyzed the global submarine landslide-related work during the period from 2001 to 2020. To achieve this objective, Science Citation Index Expand and the Social Sciences Citation Index, belonging to the WoS Core Collection, were the two bibliographic databases selected as a reference. In this study, we focused on document types, publishing languages, subject categories, journals’ productivity, countries and author, and co-occurrence keywords network. Geoscience multidisciplinary, Geochemistry Geophysics, Oceanography, Environmental Sciences, and Materials Science Multidisciplinary have been the most commonly used science categories in the past two decades. Marine Geology, Marine and Petroleum Geology, Journal of Volcanology, and Geothermal Research are the three most productive journals on submarine landslides. Marine Geology is the most active journal among all the journals. The United States, the United Kingdom, China, Germany, and France are the five most productive countries. At the institutional level, the Centre National De la Recherche Scientifique (France) is the most active institution, followed by the Chinese Academy of Sciences (China) and Helmholtz Association (Germany). Masson DG and Talling PJ from the United Kingdom contribute to the most high-quality submarine landslide-related publications. Analyzing by CiteSpace, the five largest clusters in the submarine landslide field are “gas hydrate,” “turbidity current,” “thin film,” “debris avalanche,” and “submarine canyon.” Active further research directions of submarine landslides are “south china sea,” “slump,” and “submarine mass failure.”

Immunotherapy is a hot area in cancer treatment, and one of the keys to this therapy is the identification of the right tumour-associated or tumour-specific antigen. Cluster of differentiation 24 (CD24) is an emerging tumour-associated antigen that is commonly and highly expressed in various tumours. In addition, CD24 is associated with several cancer-related signalling pathways and closely interacts with other molecules and immune cells to influence tumour progression. Monoclonal antibodies, antibody–drug conjugates (ADCs), chimeric antigen receptor (CAR) T-cell therapy, and CAR-NK cell therapy are currently available for the treatment of CD24. In this review, we summarise the existing therapeutic approaches and possible future directions targeting CD24.

Background: Patients with type 2 diabetes mellitus have a higher susceptibility for colorectal cancer and poorer prognosis, but the mechanism is still unknown. Here, we investigated the effect of ADP-ribosyltransferase 1 (ART1) on the growth of colorectal cancer in an animal model of diabetes with high norepinephrine status, as well as the potential mechanism. Methods: We evaluated the size and weight of transplanted CT26 cell tumors with different ART1 expression levels in a mouse model of diabetes, as well as the survival time. CCK8 and flow cytometry were used to evaluate the growth of CT26 cells in vitro. Western blot was performed to analyze differentially expressed proteins in the ART1-modulated pathway. Results: High levels of norepinephrine and ART1 favored the proliferation of CT26 cells in vitro and in vivo. Moreover, inhibition of norepinephrine-dependent proliferation was observed in ART1-silenced CT26 cells compared to those with normal ART1 expression. Following reduction of the serum norepinephrine level by surgery, the size and weight of transplanted CT26 cell tumors was significantly reduced compared to non-operated and sham-operated mice. Furthermore, the expression of ART1, mTOR, STAT3, and p-AKT protein in the tumor tissue of diabetic mice was higher than in non-diabetic mice. Following reduction of the norepinephrine level by renal denervation (RD), expression of the proliferation-related proteins mTOR, STAT3, p-AKT protein decreased, but no change was seen for ART1 expression. At the same concentration of norepinephrine, ART1 induced the expression of p-AKT, mTOR, STAT3, CyclinD1 and c-myc in CT26 cells in vitro. Conclusions: We conclude that faster growth of colorectal cancer in high norepinephrine conditions requires the expression of ART1, and that high ART1 expression may be a novel target for the treatment of diabetes-associated colorectal cancer.

In this study, the complete mitogenome of Grapsus albolineatus (Lamarck, 1818) (Crustacea: Grapsoidea) was sequenced. The mitogenome of G. albolineatus was a circular molecule with 15,578 bp length. Its nucleotide composition was 26.81% A, 16.37% G, 34.51% T, and 22.31% C. It comprised 13 protein-coding genes (PCGs), 22 transfer RNA (tRNA), and two ribosomal RNA (rRNA). All PCGs were initiated by ATN codons, except for the atp8 and nad1 genes. Ten PCGs used a common stop codon of TAA or TAG, and the other three ended with a truncated stop codon (a single stop nucleotide T). Phylogenetic analysis revealed that G. albolineatus was closely related to species from the genera Pachygrapsus and Metopograpsus.

Abstract. Background:. The risk for chronic kidney disease (CKD) is influenced by genetic predisposition, sex, and lifestyle. Previous research indicates that coffee is a potentially protective factor in CKD. The current study aims to investigate whether sex disparity exists in the coffee–CKD association, and whether genetic risk of CKD or genetic polymorphisms of caffeine metabolism affect this association. Methods:. A total of 359,906 participants from the UK Biobank who were enrolled between 2006 and 2010 were included in this prospective cohort study, which aimed to estimate the hazard ratios for coffee intake and incident CKD using a Cox proportional hazard model. Allele scores of CKD and caffeine metabolism were additionally adjusted for in a subsample with qualified genetic data (n = 255,343). Analyses stratified by genetic predisposition, comorbidities, and sex hormones were performed. Tests based on Bayesian model averaging were conducted to ascertain the robustness of the results. Results:. Coffee was inversely associated with CKD in a dose-dependent manner. The effects of coffee did not differ across different strata of genetic risk for CKD, but were more evident among slower genetically predicted caffeine metabolizers. Significant sex disparity was observed (P value for interaction = 0.013), in that coffee drinking was only associated with the risk reduction of CKD in females. Subgroup analysis revealed that testosterone and sex hormone-binding globulin (SHBG), but not estradiol, modified the coffee–CKD association. Conclusions:. In addition to the overall inverse coffee–CKD association that was observed in the general population, we could also establish that a sex disparity existed, in that females were more likely to experience the benefit of the association. Testosterone and SHBG may partly account for the sex disparity.

BackgroundData about real-world effects of combined therapy with sacubitril/valsartan plus dapagliflozin in patients affected by heart failure (HF) with reduced ejection fraction (HFrEF) has not been widely reported. In this article, the benefits of dapagliflozin and sacubitril/valsartan respect to improvements of cardiac function in patients with HFrEF would be investigated.MethodsHF patients prescribed sacubitril/valsartan between January 2020 and January 2022 in a tertiary teaching hospital were selected using the Computerized Patient Record System. Patients were divided into two groups according to whether they were taking dapagliflozin. Clinical parameters at baseline and during follow-up were retrospectively collected and analyzed.ResultsTotal of 136 consecutive patients were recruited for this study. 72 patients treated with sacubitril/valsartan and dapagliflozin were assigned to Group A, and another 64 patients receiving sacubitril/valsartan monotherapy were assigned to Group B. After treatment with sacubitril/valsartan plus dapagliflozin for a median follow-up period of 189 days (IQR, 180–276), significant improvements of cardiac function were achieved in Group A. Median N-terminal pro-B-type natriuretic peptide (NT-proBNP) level was significantly decreased from 2585 pg/ml (1014–3702.5) to 1260.5 pg/ml (439.8–2214.3) (P

The production of coalbed methane resources is greatly dependent on the reservoir depletion process. To improve the depressurization efficiency of deep coalbed methane (DCBM) reservoirs, the fluid production characteristics and implications of in situ stress and reservoir pressure for reservoir depletion in the eastern margin of the Ordos Basin are analyzed. The results indicate that the duration of the single-phase water production stage is overall long, with the gas declining stage occurring too early. The daily gas production volume of DCBM wells is only a few hundred m3. For DCBM reservoirs, it is considered that in situ stress, initial reservoir pressure, and critical desorption pressure significantly affect the fluid production and depressurization process. A high in situ stress in deep coal seams is likely to damage the flow conductivity of fracture systems due to the increase in effective stress during reservoir depletion. Based on the in situ stress characteristics of deep coal seams and their implications for reservoir depletion, we propose that the depressurization of DCBM reservoirs during gas production can be promoted via a new method of stress release. Slots or cavities created in coal seams by high-pressure hydraulic jet can provide space for stress release. This novel depressurization method could help improve the gas production efficiency of DCBM reservoirs.

Abstract Early human brain development can be affected by multiple prenatal factors that involve chemical exposures in utero, maternal health characteristics such as psychiatric disorders, and cancer. Breast cancer is one of the most common cancers worldwide arising pregnancy. However, it is not clear whether the breast cancer might influence the brain development of fetus. Exosomes secreted by breast cancer cells play a critical role in mediating intercellular communication and interplay between different organs. In this work, we engineered human induced pluripotent stem cells (hiPSCs)-derived brain organoids in an array of micropillar chip and probed the influences of breast cancer cell (MCF-7) derived-exosomes on the early neurodevelopment of brain. The formed brain organoids can recapitulate essential features of embryonic human brain at early stages, in terms of neurogenesis, forebrain regionalization, and cortical organization. Treatment with breast cancer cell derived-exosomes, brain organoids exhibited enhanced expression of stemness-related marker OCT4 and forebrain marker PAX6. RNA-seq analysis reflected several activated signaling pathways associated with breast cancer, medulloblastoma and neurogenesis in brain organoids induced by tumor-derived exosomes. These results suggested that breast cancer cell-derived exosomes might lead to the impaired neurodevelopment in the brain organoids and the carcinogenesis of brain organoids. It potentially implies the fetus of pregnant women with breast cancer has the risk of impaired neurodevelopmental disorder after birth.

Abstract Background To elucidate the influence of childhood asthma on adult height after consideration of genetic heterogeneity in height. Methods Based on the UK Biobank, we conducted a matched cohort study, including 13,602 European individuals with asthma diagnosed before 18 years old and 136,008 matched unexposed individuals without such an experience. Ascertainment of asthma was based on self-reported data (97.6%) or clinical diagnosis in healthcare registers (2.4%). We studied three height outcomes, including (1) the attained adult height (in centimeters), (2) the height deviation measured as the difference between a person’s rank of genetically determined height (based on generated polygenetic risk score) and their rank of attained adult height in the study population (deviation in % of height order after standardization), and (3) the presence of height deficit comparing genetically determined and attained height (yes or no). We applied linear mixed-effect models to assess the associations of asthma diagnosed at different ages with attained adult height and height deviation, and conditional logistic regression models to estimate the associations of asthma with the risk of height deficit. Results 40.07% (59,944/149,610) of the study participants were born before 1950, and most of them were men (57.65%). After controlling for multiple covariates, childhood asthma was associated with shorter attained adult height, irrespective of age at asthma diagnosis. However, in the analysis of height deviation (deviation in %), we observed the greatest height deviation among individuals with asthma diagnosed before 4 years of age (− 2.57 [95% CI − 4.14 to − 1.00] and − 2.80 [95% CI − 4.06 to − 1.54] for the age of ≤ 2 and 3–4 years, respectively). The magnitude of height deviation in relation to asthma declined thereafter and became null after age 6. Similarly, there was a statistically significant height deficit in relation to an asthma diagnosis at ages ≤ 2 and 3–4 (odds ratios = 1.21, 95% CI 1.04 to 1.40, and 1.15, 95% CI 1.02 to 1.29) but not thereafter. The result pattern was similar when separately analyzing asthma with or without inhaled glucocorticoid (ICS) use, despite that the estimates were consistently stronger among asthma individuals who used ICS. Conclusions Our results suggest a notable association of childhood asthma, primarily asthma diagnosed at an early age, with adult height, after consideration of genetic heterogeneity in height and use of ICS. This finding highlights the need for surveillance on the growth problems among children with asthma.

Abstract Background An increased susceptibility to COVID-19 has been suggested for individuals with neurodegenerative diseases, but data are scarce from longitudinal studies. Methods In this community-based cohort study, we included 96,275 participants of the UK Biobank who had available SARS-CoV-2 test results in Public Health England. Of these, 2617 had a clinical diagnosis of neurodegenerative diseases in the UK Biobank inpatient hospital data before the outbreak of COVID-19 (defined as January 31st, 2020), while the remaining participants constituted the reference group. We then followed both groups from January 31st, 2020 to June 14th, 2021 for ascertainment of COVID-19 outcomes, including any COVID-19, inpatient care for COVID-19, and COVID-19 related death. Logistic regression was applied to estimate the association between neurogenerative disease and risks of COVID-19 outcomes, adjusted for multiple confounders and somatic comorbidities. Results We observed an elevated risk of COVID-19 outcomes among individuals with a neurodegenerative disease compared with the reference group, corresponding to a fully adjusted odds ratio of 2.47 (95%CI 2.25–2.71) for any COVID-19, 2.18 (95%CI 1.94–2.45) for inpatient COVID-19, and 3.67 (95%CI 3.11–4.34) for COVID-19 related death. Among individuals with a positive test result for SARS-CoV-2, individuals with neurodegenerative diseases had also a higher risk of COVID-19 related death than others (fully adjusted odds ratio 2.08; 95%CI 1.71–2.53). Conclusion Among UK Biobank participants who received at least one test for SARS-CoV-2, a pre-existing diagnosis of neurodegenerative disease was associated with a subsequently increased risk of COVID-19, especially COVID-19 related death.

Introduction: It is urgent to make a rapid screening of infants at the highest risk for bronchopulmonary dysplasia (BPD) via some succinct postnatal biomarkers, such as Ureaplasma Urealyticum (UU) infection and chest radiograph images. Methods: A retrospective study was performed. Moderate to severe BPD or death was set as the main outcome. The association between putative variables and the main outcome were assessed by bivariate analyses and logistic regression. Results: A total of 134 infants were enrolled. Bivariate analyses showed the gestational age, birth weight, appearances of diffuse opacities or grid shadows/interstitial opacities or mass opacities or cystic lucencies on chest radiographic images, a ductal diameter ≥1.5 mm and whether UU infection was associated with BPD. After adjustment by logistic regression, the risk of BPD with gestational age, sex and specific chest-radiographic manifestations remained significant. Conclusions: Chest radiograph images (appearance of diffuse opacities or grid shadows/interstitial opacities or mass opacities or cystic lucencies) could provide a quick prediction of developing BPD in clinical practice, in addition to gestational age and sex. UU infection was not an independent risk factor for BPD.

Introduction: Bronchopulmonary dysplasia (BPD) is a devastating disease in preterm infants concurrent with neurodevelopmental disorders. Chronic hyperoxia exposure might also cause brain injury, but the evidence was insufficient. Methods: Neonatal C57BL/6J mice were exposed to hyperoxia from P0 to induce a BPD disease model. Lung histopathological morphology analyses were performed at P10, P15, and P20. Cerebral myelination was assessed using MBP (myelin basic protein, a major myelin protein), NfH (neurofilament heavy chain, a biomarker of neurofilament heavy chain), and GFAP (glial fibrillary acidic protein, a marker of astrocytes) as biomarkers by western blot and immunofluorescence. Results: Mice exposed to hyperoxia exhibited reduced and enlarged alveoli in lungs. During hyperoxia exposure, MBP declined at P10, but then increased to a comparable level to the air group at P15 and P20. Meanwhile, GFAP elevated significantly at P10, and the elevation sustained to P15 and P20. Conclusion: Neonatal hyperoxia exposure caused an arrest of lung development, as well as an obstacle of myelination process in white matter of the immature brain, with a decline of MBP in the generation period of myelin and persistent astrogliosis.

Carbonate bedrock regions represent that 14% of Earth's continental surface and carbon (C) sink in karst water plays an important role in the global C cycle due to the CO2 consumption during carbonate mineral weathering. Intensive agriculture and urbanization have led to the excessive input of nitrogen (N) into aquatic systems, while the high concentrations of inorganic C in the karst water might affect the N cycle. This paper summarized the characteristics of water in karst regions and discussed the N transformation coupled with the C cycle in the condition of high Ca2+ content, high pH, and high C/N ratios. Carbonates can consume more atmospheric and pedologic CO2 than non-carbonates because of their high solubility and high rate of dissolution, resulting in the higher average CO2 sink in karst basins worldwide than that in non-karst basins. Therefore, carbonate mineral weathering and aquatic photosynthesis are the two dominant ways of CO2 absorption, which are termed as coupled carbonate weathering. As the alkalinity and high C/N content of karst water inhibit the denitrification and mineralization processes, the karst aquatic environment is also served as the N sink. HIGHLIGHTS Karst aquatic systems contain high contents of DIC, Ca2+, Mg2+, and high pH.; C–N cycles in the karst aquatic systems are mainly related with DIC and NO3−.; Enhanced nitrification and DIC can promote aquatic communities growth.; Atmospheric CO2 sink in carbonate area is high.;

Abstract Background With the increasing number of people infected with and recovered from coronavirus disease 2019 (COVID-19), the extent of major health consequences of COVID-19 is unclear, including risks of severe secondary infections. Methods Based on 445,845 UK Biobank participants registered in England, we conducted a matched cohort study where 5151 individuals with a positive test result or hospitalized with a diagnosis of COVID-19 were included in the exposed group. We then randomly selected up to 10 matched individuals without COVID-19 diagnosis for each exposed individual (n = 51,402). The life-threatening secondary infections were defined as diagnoses of severe secondary infections with high mortality rates (i.e., sepsis, endocarditis, and central nervous system infections) from the UK Biobank inpatient hospital data, or deaths from these infections from mortality data. The follow-up period was limited to 3 months after the initial COVID-19 diagnosis. Using a similar study design, we additionally constructed a matched cohort where exposed individuals were diagnosed with seasonal influenza from either inpatient hospital or primary care data between 2010 and 2019 (6169 exposed and 61,555 unexposed individuals). After controlling for multiple confounders, Cox models were used to estimate hazard ratios (HRs) of life-threatening secondary infections after COVID-19 or seasonal influenza. Results In the matched cohort for COVID-19, 50.22% of participants were male, and the median age at the index date was 66 years. During a median follow-up of 12.71 weeks, the incidence rate of life-threatening secondary infections was 2.23 (123/55.15) and 0.25 (151/600.55) per 1000 person-weeks for all patients with COVID-19 and their matched individuals, respectively, which corresponded to a fully adjusted HR of 8.19 (95% confidence interval [CI] 6.33–10.59). The corresponding HR of life-threatening secondary infections among all patients with seasonal influenza diagnosis was 4.50, 95% CI 3.34–6.08 (p for difference < 0.01). Also, elevated HRs were observed among hospitalized individuals for life-threatening secondary infections following hospital discharge, both in the COVID-19 (HR = 6.28 [95% CI 4.05–9.75]) and seasonal influenza (6.01 [95% CI 3.53–10.26], p for difference = 0.902) cohorts. Conclusion COVID-19 patients have increased subsequent risks of life-threatening secondary infections, to an equal extent or beyond risk elevations observed for patients with seasonal influenza.

Abstract Background The prognosis of patients with advanced gastric cancer (GC) remains unsatisfactory owing to distant metastasis and resistance to concurrent systemic therapy. Cancer-associated fibroblasts (CAFs), as essential participators in the tumor microenvironment (TME), play a vital role in tumor progression. Thus, CAFs-targeting therapy is appealing for remodeling TME and sensitizing GC to conventional systemic therapy. Methods Amphiphilic SN38 prodrug polymeric micelles (PSN38) and encapsulated the hydrophobic esterase-responsive prodrug of Triptolide (TPL), triptolide-naphthalene sulfonamide (TPL-nsa), were synthesized to form PSN38@TPL-nsa nanoparticles. Then, CAFs were isolated from fresh GC tissues and immortalized. TPL at low dose concentration was used to investigate its effect on CAFs and CAFs-induced GC cells proliferation and migration. The synergistic mechanism and antitumor efficiency of SN38 and TPL co-delivery nanoparticle were investigated both in vitro and in vivo. Results Fibroblast activation protein (FAP), a marker of CAFs, was highly expressed in GC tissues and indicated poorer prognosis. TPL significantly reduced CAFs activity and inhibited CAFs-induced proliferation, migration and chemotherapy resistance of GC cells. In addition, TPL sensitized GC cells to SN38 treatment through attenuated NF-κB activation in both CAFs and GC cells. PSN38@TPL-nsa treatment reduced the expression of collagen, FAP, and α-smooth muscle actin (α-SMA) in tumors. Potent inhibition of primary tumor growth and vigorous anti-metastasis effect were observed after systemic administration of PSN38@TPL-nsa to CAFs-rich peritoneal disseminated tumor and patient-derived xenograft (PDX) model of GC. Conclusion TPL suppressed CAFs activity and CAFs-induced cell proliferation, migration and chemotherapy resistance to SN38 of GC. CAFs-targeted TPL and SN38 co-delivery nanoparticles exhibited potent efficacy of antitumor and reshaping TME, which was a promising strategy to treat advanced GC. Graphical Abstract

Abstract Aims Sacubitril/valsartan significantly reduced heart failure (HF) hospitalization and cardiovascular mortality in a randomized controlled trial. However, little is known about real‐world efficacy and safety of sacubitril/valsartan in Chinese patients with HF with reduced ejection fraction (HFrEF). We aimed to evaluate whether sacubitril/valsartan could improve cardiac function in Chinese patients with HFrEF in a tertiary hospital in China. Methods and results Patients with HFrEF receiving sacubitril/valsartan in our hospital between January 2018 and January 2020 were recruited in the present study. We retrospectively collected and analysed all clinical parameters at baseline and during follow‐up. A total of 100 consecutive patients (73% male) with HFrEF were recruited in the present study. During a median follow‐up period of 365 days [interquartile range (IQR), 346–378], a pronounced improvement of cardiac function was achieved. New York Heart Association classification was significantly improved (P

Near-infrared (NIR)-emitting mechanoluminescence (ML) materials are highly desirable since they are biological transparency and suitable for deep-imaging inside biological tissues. So far, NIR emission can be found in very limited number ML materials. Moreover, reported NIR ML materials suffer from limitations associated with the incompetence in self-reproducibility. Herein, we observe sustainable and self-recoverable NIR ML emission in pulsed laser deposition (PLD) method grown ZnS:Mn film, for the first time. ML emission in ZnS:Mn can be explained by the piezoelectricity-induced detrapping model. Broad ML emission covering both red and NIR ranges arises from the presence of (Mn)n clusters, which facilitates the energy transfer from excited Mn2+ ions to them. During the PLD growth, high laser fluence and deposition rate contribute to the formation of (Mn)n clusters, which was verified by electron paramagnetic resonance EPR and X-ray photoelectron spectroscopy XPS analysis. The device exhibits durable NIR ML over 105 repeated mechanical stresses, suggesting new possibilities aiming for constructing self-recoverable NIR ML materials.

Teamwork is a vital aspect of human life, including a set of concrete behaviors which could be divided into various categories such as task performance, job dedication, backing up behavior, and monitoring. As an essential psychological factor could form team members to adapt to environmental changes, self-regulation has a marked impact on teamwork results. However, why self-regulation could affect results of teamwork in real life and how self-regulation influence the concrete teamwork behaviors remains unclear. This study recorded and extracted participants’ detailed gaming behaviors in Defense of the Ancients 2 (DOTA 2), which is an example of real-life teamwork scenario. The sample consisted of 59 DOTA 2 players with relative low-level self-regulation (93.22% male) and 59 with relative high-level self-regulation (96.61% male). Controlling confounding factors, we explored behavioral differences between the two groups in different types of heroes. Results showed that self-regulation influenced specific gaming behaviors including the categories of task performance, job dedication, and backing up behavior, but not including monitoring. Additionally, these impacts of self-regulation varied by hero type. These results demonstrate the different impacts of self-regulation on different categories of teamwork behaviors, and these impacts are considerably determined by individual’s role in the team. These findings shed light on the mechanism of the teamwork performance improvement caused by self-regulation and provide new insights into understanding the different impact patterns of self-regulation in different real-life tasks and responsibilities.

ObjectiveThe objective of this study was to investigate occupational blood-borne pathogen exposure among dental nurses and their attitudes toward infected patients, as well as the effectiveness of the training course, to provide a scientific basis for improving the quality of safety management in the dental hospital.Materials and methodsThe study was conducted using questionnaires administered from November 2019 to December 2019 in three hospitals in Sichuan Province, China. Frequencies for answers were calculated and presented as percentages.ResultsIn total, 257 valid questionnaires were returned. Most (61.9%) nurses stated that they were involved in occupational exposure. Among them, 154 had experienced sharp injuries, and the syringe needle was the most common instrument for injuries (45.8%). Twenty-two individuals had mucosal exposure, and the proportion of eye exposure was the highest (90.9%). Only associations between training and mucosal membrane exposure were found; however, the relevance was weak (r = 0.141). Of the participants, 86.4% felt morally responsible for taking care of patients with infectious diseases, and most (92.6%) said they would continue with this career.ConclusionOccupational exposure, particularly to sharp injuries, was common in medical care among dental nurses; however, vocational training had little effect on their incidence. As dental nurses still have positive attitudes toward patients with infectious diseases, more effective training should be conducted.

Reflective displays have recently attracted more and more attention because of the advantages of low power consumption and eye protection. Among them, electrowetting display (EWD) is the most potential reflective display technology due to its full color and video speed advantages. However, filling models of oil and polar liquids in EWD fabrication were rarely reported. In this paper, a phase change filling model was proposed, and its related equipment was designed and manufactured. The efficiency of phase change filling model has a significant advantage compared to conventional filling models, which can finish the whole process of filling and coupling for 400*500 mm panel within 270 s while the efficiency of other filling models is over 10 min. Since the process of oil filled into the pixels was released into the air environment, the dosing method was significantly enriched, and dosing accuracy was more controllable. The experimental results showed that, a good response time and a high pixel aperture ratio of 31.78 ms and 68.2% can be obtained, respectively.

BackgroundGeriatric care professionals were forced to rapidly adopt the use of telemedicine technologies to ensure the continuity of care for their older patients in response to the COVID-19 pandemic. However, there is little current literature that describes how telemedicine technologies can best be used to meet the needs of geriatric care professionals in providing care to frail older patients, their caregivers, and their families. ObjectiveThis study aims to identify the benefits and challenges geriatric care professionals face when using telemedicine technologies with frail older patients, their caregivers, and their families and how to maximize the benefits of this method of providing care. MethodsThis was a mixed methods study that recruited geriatric care professionals to complete an online survey regarding their personal demographics and experiences with using telemedicine technologies and participate in a semistructured interview. Interview responses were analyzed using the Consolidated Framework for Implementation Research (CFIR). ResultsQuantitative and qualitative data were obtained from 30 practicing geriatric care professionals (22, 73%, geriatricians, 5, 17%, geriatric psychiatrists, and 3, 10%, geriatric nurse practitioners) recruited from across the Greater Toronto Area. Analysis of interview data identified 5 CFIR contextual barriers (complexity, design quality and packaging, patient needs and resources, readiness for implementation, and culture) and 13 CFIR contextual facilitators (relative advantage, adaptability, tension for change, available resources, access to knowledge, networks and communications, compatibility, knowledge and beliefs, self-efficacy, champions, external agents, executing, and reflecting and evaluating). The CFIR concept of external policy and incentives was found to be a neutral construct. ConclusionsThis is the first known study to use the CFIR to develop a comprehensive narrative to characterize the experiences of Ontario geriatric care professionals using telemedicine technologies in providing care. Overall, telemedicine can significantly enable most of the geriatric care that is traditionally provided in person but is less useful in providing specific aspects of geriatric care to frail older patients, their caregivers, and their families.

Summary: Water technological progress contributes a lot to water conservation. Most studies have overestimated its contribution by ignoring its scale effect on economic growth, leading to the increase in water consumption. To quantify the trade-off of water technological progress, we combine the macroeconomic model with the environmental model to analyze both the scale effect and the intensity effect of water technological progress. Results show that the intensity effect has reduced China’s water consumption by 612.256 × 109 m3 from 2003 to 2020, while the scale effect increases China’s water consumption by 189.911 × 109 m3. The contribution of technological progress varies among regions in China. The industrial structure effect inhibits water consumption, second to the water-saving effect of water technological progress. The input effect increases water consumption owing to the particularly striking promotion of the effect of capital input. Some policy recommendations are given to mitigate the trade-off of water technological progress and regional disparity.

PurposeTo seek novel diagnostic approaches, we improved the workflow of cell-free DNA (cfDNA) sequencing and evaluated its feasibility in vitreoretinal lymphoma (VRL) specimens; the profile of mutations was preliminarily analyzed for potential diagnostic value.MethodsThe study was a diagnostic trial. 23 eyes of 23 patients with VRL and 25 eyes of 25 patients with inflammatory eye diseases were enrolled. Approximate 500μl undiluted vitreous humor and 10ml diluted vitreous fluid was obtained through diagnostic vitrectomy and sent for cytopathological examinations. 500μl of the diluted vitreous fluid was spared for cfDNA sequencing. For cfDNA sequencing, DNA fragmentation procedure was added to the workflow to improve the extraction efficiency; mutations detected were analyzed for potential diagnostic model. The sensitivity and specificity of the cytopathology and cfDNA sequencing were compared. The clinical manifestations were preliminarily analyzed for potential correlations with the genotypes.ResultsCfDNA sequencing was accomplished in 23 eyes with VRL and 20 eyes with inflammatory eye diseases. VRL-related mutated genes included MYD88 (18 eyes, 78%), ETV6 (11 eyes, 48%), PIM1 (11 eyes,48%), BTG2 (7 eyes, 30%), IRF4 (7 eyes, 30%), CD79B (6 eyes, 26%), LRP1B (6 eyes, 26%), etc. Logistic regression based on the mutations of MYD88 and ETV6 was of the potential for the diagnosis of VRL (P

Surface oxygen vacancy (OV) plays a pivotal role in the activation of molecular oxygen and separation of electrons and holes in photocatalysis. Herein, carbonaceous materials-modified MoO2 nanospheres with abundant surface OVs (MoO2/C-OV) were successfully synthesized via glucose hydrothermal processes. In situ introduction of carbonaceous materials triggered a reconstruction of the MoO2 surface, which introduced abundant surface OVs on the MoO2/C composites. The surface oxygen vacancies on the obtained MoO2/C-OV were confirmed via electron spin resonance spectroscopy (ESR) and X-ray photoelectron spectroscopy (XPS). The surface OVs and carbonaceous materials boosted the activation of molecular oxygen to singlet oxygen (1O2) and superoxide anion radical (•O2−) in selectively photocatalytic oxidation of benzylamine to imine. The conversion of benzylamine was 10 times that of pristine MoO2 nanospheres with a high selectivity under visible light irradiation at 1 atm air pressure. These results open an avenue to modify Mo-based materials for visible light-driven photocatalysis.