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Given the association of Epstein-Barr virus (EBV) with subjective perception of fatigue and demyelination in clinical conditions, the question about potential subclinical effects in the adult general population remains open. We investigate the association between individuals’ EBV immune response and perceived fatigue in a community dwelling cohort (n = 864, age 62 ± 10 years old; 49% women) while monitoring brain tissue properties. Fatigue levels are assessed with the established fatigue severity scale, the EBNA-1 and VCA p18 immunoglobulin G (IgG) chronic response – with multiplex serology and the estimates of local brain volume, myelin content, and axonal density - using relaxometry- and multi-shell diffusion-based magnetic resonance imaging (MRI). In our analysis we adjust for the effects of demographic and cardiovascular risk factors, sleep apnea, depression, and polygenic risk score for multiple sclerosis. We demonstrate that EBNA-1 IgG levels are positively associated with perceived levels of fatigue, whilst VCA p18 IgG levels show a positive correlation with myelin content and a negative one with an estimate of axonal g-ratio in male participants. In the context of EBVs immune response, the polygenic risk for multiple sclerosis is not associated with increased fatigue levels, brain myelination or atrophy. Our findings bring empirical evidence about the potential role of EBVs chronic immune response in perceived fatigue and hint towards a protective role of myelination specific for men. They underscore the added value of advanced assessment of brain tissue microstructure in uncovering the mechanisms behind frequent fatigue complaints associated with EBV infection and multiple sclerosis.

Hydrochlorothiazide (HCTZ) is a widely utilized diuretic for the treatment of hypertension. The photosensitivity of HCTZ has been recognized for six decades, with UVA being considered the primary culprit. However, the precise molecular mechanism of HCTZ sensitizing skin to UV radiation remains unknown. In this study, we demonstrate that HCTZ exacerbates UVB-induced photosensitivity in normal skin by disrupting the DNA damage response, a crucial network responsible for maintaining epidermal homeostasis. Here, we found that HCTZ aggravates UVB-induced mouse skin damage. Through transcriptomic and proteomic profiling, we have found that the cell cycle and p53 signaling pathway may contribute to the photosensitivity caused by HCTZ. In keratinocytes, HCTZ promotes the transition from G1 to S phase and inhibits the p53 signaling pathway after exposure to UV radiation. We have found that HCTZ enhances the accumulation of DNA damage induced by UVB and impairs nucleotide excision repair (NER), which is responsible for repairing UVB-induced DNA lesions, by inhibiting the expression of NER-related genes and shortening the duration of G1 phase. Furthermore, pharmacologically inducing G1 arrest eliminates HCTZ-induced accumulation of damaged DNA. These findings unveil an unknown mechanism through which HCTZ impairs NER and interferes with UVB-induced cell cycle arrest, ultimately leading to improper response towards DNA damage and increased skin sensitivity.

Objective: This study aimed to accurately segment teeth under complex oral conditions, including complex structural interference among adjacent teeth or malocclusion conditions, such as tooth rotation and displacement caused by dental crowding. Study design: Cone-beam computed tomography (CBCT) images were obtained from 19 patients with complex oral conditions, and a three-step solution was proposed. This study used a global convex level-set model to extract bony tissue and developed a flexible curve extraction method for separating neighbouring teeth under complex structural interference. In addition, a local level-set model with adaptive edge feature enhancement was proposed to segment individual teeth precisely. This model adaptively enhances edge features based on the structure of the root boundary and accurately distinguishes between the close-contact root and alveolar bone resulting from tooth rotation or displacement. Results: The experimental results showed that the average Dice similarity coefficient values for incisors, canines, premolars, and molars were 93.30%, 93.47%, 93.24%, and 93.89%, respectively, and the average tooth centroid distances were 0.66, 0.61, 0.87, and 0.80 mm, respectively. Conclusion: The proposed method can effectively segment teeth without relying on highly precise annotated datasets, yielding satisfactory results even under complex structural interference between adjacent teeth or tooth rotation and displacement caused by dental crowding. It is more robust than the other methods and provides valuable data for further research and clinical practice.

The reinforced concrete (RC) wall coupled with steel side columns (SSC) using steel coupling beams were studied both experimentally and numerically. A 1/4 scaled 5-story test model was constructed and tested to failure under reversed lateral cyclic and constant axial loads. Test results proved that the coupling mechanism can be effectively realized in this unique coupled structural system involving only one wall pier. In order to reveal more seismic response characteristics in addition to the test results, numerical parametric studies were conducted based on the validated finite element modeling techniques. Results indicate the medium levels of axial load ratio and span-to-depth ratio of the steel coupling beam, or low level of wall aspect ratio, can lead to acceptable lateral load capacity and displacement ductility of the RC wall and SSC coupled structural system.

Summary: Background: Comorbidity, frailty, and decreased cognitive function lead to a higher risk of death in elderly patients (more than 65 years of age) during acute medical events. Early and accurate illness severity assessment can support appropriate decision making for clinicians caring for these patients. We aimed to develop ELDER-ICU, a machine learning model to assess the illness severity of older adults admitted to the intensive care unit (ICU) with cohort-specific calibration and evaluation for potential model bias. Methods: In this retrospective, international multicentre study, the ELDER-ICU model was developed using data from 14 US hospitals, and validated in 171 hospitals from the USA and Netherlands. Data were extracted from the Medical Information Mart for Intensive Care database, electronic ICU Collaborative Research Database, and Amsterdam University Medical Centers Database. We used six categories of data as predictors, including demographics and comorbidities, physical frailty, laboratory tests, vital signs, treatments, and urine output. Patient data from the first day of ICU stay were used to predict in-hospital mortality. We used the eXtreme Gradient Boosting algorithm (XGBoost) to develop models and the SHapley Additive exPlanations method to explain model prediction. The trained model was calibrated before internal, external, and temporal validation. The final XGBoost model was compared against three other machine learning algorithms and five clinical scores. We performed subgroup analysis based on age, sex, and race. We assessed the discrimination and calibration of models using the area under receiver operating characteristic (AUROC) and standardised mortality ratio (SMR) with 95% CIs. Findings: Using the development dataset (n=50 366) and predictive model building process, the XGBoost algorithm performed the best in all types of validations compared with other machine learning algorithms and clinical scores (internal validation with 5037 patients from 14 US hospitals, AUROC=0·866 [95% CI 0·851–0·880]; external validation in the US population with 20 541 patients from 169 hospitals, AUROC=0·838 [0·829–0·847]; external validation in European population with 2411 patients from one hospital, AUROC=0·833 [0·812–0·853]; temporal validation with 4311 patients from one hospital, AUROC=0·884 [0·869–0·897]). In the external validation set (US population), the median AUROCs of bias evaluations covering eight subgroups were above 0·81, and the overall SMR was 0·99 (0·96–1·03). The top ten risk predictors were the minimum Glasgow Coma Scale score, total urine output, average respiratory rate, mechanical ventilation use, best state of activity, Charlson Comorbidity Index score, geriatric nutritional risk index, code status, age, and maximum blood urea nitrogen. A simplified model containing only the top 20 features (ELDER-ICU-20) had similar predictive performance to the full model. Interpretation: The ELDER-ICU model reliably predicts the risk of in-hospital mortality using routinely collected clinical features. The predictions could inform clinicians about patients who are at elevated risk of deterioration. Prospective validation of this model in clinical practice and a process for continuous performance monitoring and model recalibration are needed. Funding: National Institutes of Health, National Natural Science Foundation of China, National Special Health Science Program, Health Science and Technology Plan of Zhejiang Province, Fundamental Research Funds for the Central Universities, Drug Clinical Evaluate Research of Chinese Pharmaceutical Association, and National Key R&D Program of China.

Summary: Background: Dementia is a serious complication in patients with diabetes-associated cognitive dysfunction (DACD). In this study, we aim to explore the protective effect of exercise on DACD in diabetic mice, and the role of NDRG2 as a potential guarder for reversing the pathological structure of neuronal synapses. Methods: Seven weeks of standardized exercise at moderate intensity was carried out using an animal treadmill in the vehicle + Run and STZ + Run groups. Based on quantitative transcriptome and tandem mass tag (TMT) proteome sequencing, weighted gene co-expression analysis (WGCNA) and gene set enrichment analysis (GSEA) were used to investigate the activation of complement cascades to injury neuronal synaptic plasticity. Golgi staining, Western blotting, immunofluorescence staining, and electrophysiology were used to verify the reliability of sequencing data. The role of NDRG2 was assessed by overexpressing or inhibiting the NDRG2 gene in vivo. Moreover, we estimated the cognitive function in diabetic or normal patients using DSST scores. Findings: Exercise reversed the injury of neuronal synaptic plasticity and the downregulation of astrocytic NDRG2 in diabetic mice, which succeeded in attenuating DACD. The deficiency of NDRG2 aggravated the activation of complement C3 by accelerating the phosphorylation of NF-κB, ultimately leading to synaptic injury and cognitive dysfunction. Conversely, the overexpression of NDRG2 promoted astrocytic remodeling by inhibiting complement C3, thus attenuating synaptic injury and cognitive dysfunction. Meanwhile, C3aR blockade rescued dendritic spines loss and cognitive deficits in diabetic mice. Moreover, the average DSST score of diabetic patients was significantly lower than that of non-diabetic peers. Levels of complement C3 in human serum were elevated in diabetic patients compared to those in non-diabetic patients. Interpretation: Our findings illustrate the effectiveness and integrative mechanism of NDRG2-induced improvement of cognition from a multi-omics perspective. Additionally, they confirm that the expression of NDRG2 is closely related to cognitive function in diabetic mice and the activation of complement cascades accelerated impairment of neuronal synaptic plasticity. NDRG2 acts as a regulator of astrocytic-neuronal interaction via NF-κB/C3/C3aR signaling to restore synaptic function in diabetic mice. Funding: This study was supported by the National Natural Science Foundation of China (No. 81974540, 81801899, 81971290), the Key Research and Development Program of Shaanxi (Program No. 2022ZDLSF02-09) and Fundamental Research Funds for the Central Universities (Grant No. xzy022019020).

Summary: Genome-wide association studies (GWASs) have demonstrated that most common diseases have a strong genetic component from many genetic variants each with a small effect size. GWAS summary statistics have allowed the construction of polygenic scores (PGSs) estimating part of the individual risk for common diseases. Here, we propose to improve PGS-based risk estimation by incorporating genetic ancestry derived from genome-wide genotyping data. Our method involves three cohorts: a base (or discovery) for association studies, a target for phenotype/risk prediction, and a map for ancestry mapping; successively, (1) it generates for each individual in the base and target cohorts a set of principal components based on the map cohort—called mapped PCs, (2) it associates in the base cohort the phenotype with the mapped-PCs, and (3) it uses the mapped PCs in the target cohort to generate a phenotypic predictor called the ancestry score. We evaluated the ancestry score by comparing a predictive model using a PGS with one combining a PGS and an ancestry score. First, we performed simulations and found that the ancestry score has a greater impact on traits that correlate with ancestry-specific variants. Second, we showed, using UK Biobank data, that the ancestry score improves genetic prediction for our nine phenotypes to very different degrees. Third, we performed simulations and found that the more heterogeneous the base and target cohorts, the more beneficial the ancestry score is. Finally, we validated our approach under realistic conditions with UK Biobank as the base cohort and Swiss individuals from the CoLaus|PsyCoLaus study as the target cohort.

Background: Sepsis remains an unacceptably high mortality due to the lack of biomarkers for predicting septic outcomes in the early period. Mitochondrial redox states play a pivotal role in this condition and are disturbed early in the development of sepsis. Here, we hypothesized that visualizing mitochondrial redox states via resonance Raman spectroscopy (RRS) could identify septic outcomes at an early time point. Sepsis was induced by cecal ligation and puncture (CLP). We applied RRS analysis at baseline and 30 min, 1 h, 2 h, 4 h, and 6 h after CLP, and the mitochondrial redox states were identified. The levels of blood lactate as a predictor in sepsis were assessed. Our study is the first to reveal the possibility of in vivo detection of the mitochondrial redox state by using RRS in septic mice. The peak area for the Raman reduced mitochondrial fraction, the indicator of mitochondrial redox states, fluctuated significantly at 2 h after CLP. This fluctuation occurred earlier than the change in lactate level. Moreover, this fluctuation had higher prognostic accuracy for mortality than the lactate level during sepsis and could be a novel diagnostic marker for predicting septic outcomes according to the cutoff value of 1.059, which had a sensitivity of 80% and a specificity of 90%. Objectives: To explore an effective indicator concerning mitochondrial redox states in the early stage of sepsis and to predict septic outcomes accurately in vivo using non-invasive and label-free Resonance Raman spectroscopy (RRS) analysis. Methods: Mitochondria, primary skeletal muscle cells andex-vivo muscles harvested from gastrocnemius were detected mitochondrial redox states respectively by using RRS. Sepsis was induced by cecal ligation and puncture (CLP). We applied RRS analysis at baseline and 30 min, 1 h, 2 h, 4 h, and 6 h after CLP, and the mitochondrial redox states were identified. The levels of blood lactate as a predictor in sepsis were assessed. The predictive correlation of mitochondrial redox states on mortality, inflammation and organ dysfunction was further assessed. Results: Mitochondrial redox states were clearly recognized in ex-vivo gastrocnemius muscles as well as purified mitochondria and primary skeletal muscle cells by using RRS. The peak area for the Raman reduced mitochondrial fraction, the indicator of mitochondrial redox states, fluctuated significantly at 2 h after CLP. This fluctuation occurred earlier than the change in lactate level. Moreover, this fluctuation had higher prognostic accuracy for mortality than the lactate level during sepsis and could be a novel diagnostic marker for predicting septic outcomes according to the cutoff value of 1.059, which had a sensitivity of 80% and a specificity of 90%. Conclusions: This study demonstrated that monitoring mitochondrial redox states using RRS as early as 2 h could indicate outcomes in septic mice. These data may contribute to developing a non-invasive clinical device concerning mitochondrial redox states by using bedside-RRS.

Most of the existing methods neglect their complementary relation and only use welding pool images to detect welding defects. Therefore, a new triple pseudo-siamese network to improve identification performance using their complementarity is proposed in this paper. The network consists of three branches that extract the effective features of welding pool image, sound, current and voltage, respectively. Moreover, we employ a convolutional block attention module (CBAM) and propose cross-modal attention (CMA) to focus on the vital regions of the welding pool image. To train our model, the experimental setup was first designed. Then, it was deployed in an actual body production workshop of high-speed train to collect welding pool images, as well as sound and current and voltage data. Hence, a new dataset for detecting welding defects is presented. Experimental results on the dataset indicate that the proposed model can effectively detect different defects and actions. Furthermore, when the output of the shallow layer, the layer near the input layer, is fed into the CBAM and the output of the deep layer, the layer near the output layer, is fed into the CMA. In addition, they are highly complementary to each other.

Emerging base editing technology exploits CRISPR RNA-guided DNA modification effects for highly specific C > T conversion, which has been used to efficiently disrupt gene expression. These tools can enhance synthetic T cell immunity by restricting specificity, addressing histocompatibility leukocyte antigen (HLA) barriers, and promoting persistence. We report lentiviral delivery of a hepatitis B-virus (HBV)-specific recombinant T cell receptor (rTCR) and a linked CRISPR single-guide RNA for simultaneous disruption of endogenous TCRs (eTCRs) when combined with transient cytosine deamination. Discriminatory depletion of eTCR and coupled expression of rTCR resulted in enrichment of HBV-specific populations from 55% (SEM, ±2.4%) to 95% (SEM, ±0.5%). Intensity of rTCR expression increased 1.8- to 2.9-fold compared to that in cells retaining their competing eTCR, and increased cytokine production and killing of HBV antigen-expressing hepatoma cells in a 3D microfluidic model were exhibited. Molecular signatures confirmed that seamless conversion of C > T (G > A) had created a premature stop codon in TCR beta constant 1/2 loci, with no notable activity at predicted off-target sites. Thus, targeted disruption of eTCR by cytosine deamination and discriminatory enrichment of antigen-specific T cells offers the prospect of enhanced, more specific T cell therapies against HBV-associated hepatocellular carcinoma (HCC) as well as other viral and tumor antigens.

Human coronaviruses (HCoVs), including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have been resulting in global epidemics with heavy morbidity and mortality. Unfortunately, there are currently no specific medicines that can better treat these coronaviruses. Drug repurposing is an effective and economical strategy for drug discovery from existing drugs, natural products, and synthetic compounds. In this review, the broad-spectrum antiviral activity of valinomycin (VAL), especially its activity against coronaviruses such as SARS-CoV, MERS-CoV, human coronavirus OC43 (HCoV-OC43), were summarized, it highlights that VAL has tremendous potential for use as a novel antiviral agent against SARS-CoV-2.

Background: Oxidative stress-induced cardiomyocytes apoptosis is a key pathological process in ischemic heart disease. Glutathione reductase (GR) reduces glutathione disulfide to glutathione (GSH) to alleviate oxidative stress. Ginsenoside Rb1 (GRb1) prevents the apoptosis of cardiomyocytes; however, the role of GR in this process is unclear. Therefore, the effects of GRb1 on GR were investigated in this study. Methods: The antiapoptotic effects of GRb1 were evaluated in H9C2 cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, annexin V/propidium iodide staining, and Western blotting. The antioxidative effects were measured by a reactive oxygen species assay, and GSH levels and GR activity were examined in the presence and absence of the GR inhibitor 1,3-bis-(2-chloroethyl)-1-nitrosourea. Molecular docking and molecular dynamics simulations were used to investigate the binding of GRb1 to GR. The direct influence of GRb1 on GR was confirmed by recombinant human GR protein. Results: GRb1 pretreatment caused dose-dependent inhibition of tert-butyl hydroperoxide-induced cell apoptosis, at a level comparable to that of the positive control N-acetyl-L-cysteine. The binding energy between GRb1 and GR was positive (−6.426 kcal/mol), and the binding was stable. GRb1 significantly reduced reactive oxygen species production and increased GSH level and GR activity without altering GR protein expression in H9C2 cells. Moreover, GRb1 enhanced the recombinant human GR protein activity in vitro, with a half-maximal effective concentration of ≈2.317 μM. Conversely, 1,3-bis-(2-chloroethyl)-1-nitrosourea co-treatment significantly abolished the GRb1's apoptotic and antioxidative effects of GRb1 in H9C2 cells. Conclusion: GRb1 is a potential natural GR agonist that protects against oxidative stress–induced apoptosis of H9C2 cells. Keywords: Apoptosis, Ginsenoside Rb1, Glutathione reductase, H9C2, Oxidative stress

The effect of manure application on the distribution and accumulation of antibiotic resistance genes (ARGs) in tissue of root vegetables remains unclear, which poses a bottleneck in assessing the health risks from root vegetables due to application of manure. Towards this goal, experiments were conducted in pots to investigate the distribution and bioaccumulation of ARGs in carrot tissues due to application of pig manure. The 144 ARGs targeting nine types of antibiotics were quantified by high throughput qPCR in the soil and plant samples. The rhizosphere was a hot spot for ARGs enrichment in the manured soil. The abundance, diversity, and bioaccumulation factors of ARGs in the phyllosphere were significantly higher than those of carrot root skin and tuber. Manure application increased bioaccumulation of 12 ARGs and 2 MGEs in carrot tuber with 124 the highest factor. The application of manure increased transfer of 10 ARGs and 3 MGEs from carrot skin to inner tuber by factors of 0.1–11.8. The average gene copy number of ARGs of per gram carrot root was about 4.8 × 104 and 1.1 × 106 in the control and the manured treatment, respectively. Children and adults may co-ingest 2.7 × 107 and 3.2 × 107 of ARGs copies/d from carrots grown with pig manure, using estimated human intake values. However, peeling may reduce the intake of ARGs by 28–91% and of MGEs by 46–59%. In conclusion, the application of pig manure increased the accumulation of ARGs in the skin of carrots, whereas peeling was an effective strategy to reduce the risk.

With the development of manufacturing industry, more and more torque tools are used in various industrial fields, such as torque wrench, torque multiplier, hydraulic torque wrench, electric torque wrench, various torque sensors, etc. The calibration of these tools is related to the quality of manufacturing products. National institute of metrology of China has established several torque standard devices and carried out calibration of various torque tools. This paper introduces the related work.

A zero-valent iron/rectorite nanocomposite (NZVI/rectorite) was developed as a heterogeneous H2O2 catalyst for P-chlorophenol degradation. The physicochemical properties of NZVI/rectorite were characterized by various techniques including X-ray diffraction, scanning electron microscopy, transmission electron microscopy, energy-dispersive spectrometry, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and Brunauer–Emmett–Teller analysis. Results showed that NZVI sphere nanoparticles were successfully loaded on the rectorite surface with less aggregation and good dispersion. Moreover, compared with acid-leached rectorite (30.91 m2/g), the NZVI/rectorite appeared to have larger surface area (50.75 m2/g). In addition, the effects of pH, reaction time, initial P-chlorophenol concentration, catalyst amount, and H2O2 dosage on the P-chlorophenol degradation were systematically investigated. Results showed that NZVI/rectorite presents better properties for the degradation and mineralization of P-chlorophenol compared with pristine NZVI due to the large surface area, low aggregation, and good dispersion of the former. The degradation mechanisms of P-chlorophenol by NZVI/rectorite were adsorption and reduction coupled with a Fenton-like reaction. Four successive runs of the stability and regeneration study also showed that the NZVI/rectorite were unchanged even after 100% of P-chlorophenol degradation ratio. This study has extended the application of NZVI/rectorite as environment function material for the removal of P-chlorophenol from the environment. Keywords: Nano zero-valent iron, Rectorite, Heterogeneous Fenton oxidation, P-chlorophenol degradation

Objective: The aim of this study was to reduce or eliminate the stressors to enhance nursing students’ clinical learning experience through implementation of an iterative approach that developed a personalised response to student stress. Methods: A prospective cohort research design was applied to collect data from a sample of undergraduate nursing students across the four study years. An iterative approach was employed to improve students’ learning experience and the Stressors in Nursing Students Scale-Chinese Version (SINS-CN) was used to measure student stress. Key problems encountered by students were identified, refined and the responding solutions were worked out and implemented among this group of students through their first year to fourth year. Results: The overall SINS-CN mean score (2.17–2.82) of students was declined to a moderate level. Conclusions: Having implemented iterative approach to address factors that led to stressful environments encountered by the nursing students, the overall stress score and each sub-dimension score decreased significantly. Therefore, it is recommended that this approach could be adopted by other colleagues in the nursing arena around the world. Keywords: Clinical Clerkship, Nursing, Nursing education, Stressors, Students

The efficacy and safety of normal saline (NS) for fluid therapy in critically ill patients remain controversy. In this review, we summarized the evidence of randomized controlled trials (RCTs) which compared NS with other solutions in critically ill patients. The results showed that when compared with 6% hydroxyethyl starch (HES), NS may reduce the onset of acute kidney injury (AKI). However, there is no significant different in mortality and incidence of AKI when compared with 10% HES, albumin and buffered crystalloid solution. Therefore, it is important to prescribe intravenous fluid for patients according to their individual condition.

The Abernethy malformation is a rare congenital malformation defined by the presence of an extrahepatic portosystemic shunt. Although most patients are asymptomatic, clinical encephalopathy is present in 15% of cases. We present a patient with type 2 Aber-nethy malformation, hyperammonemia, and encephalopathy. Shunt closure was performed successfully using interventional angiography; however, hyperammonemia recurred 3 months later. The diagnosis of Abernethy malformation can be made easily, but the ideal patient management strategy has not yet been established. This is the first reported patient with recurrence of hyperam-monemia after interventional treatment; we discuss the therapeutic options for Abernethy malformation.

Background: Peanut (Arachis hypogaea L.) is an important economic and oilseed crop. Long-term rainless conditions and seasonal droughts can limit peanut yields and were conducive to preharvest aflatoxin contamination. To elucidate the molecular mechanisms by which peanut responds and adapts to water limited conditions, we isolated and characterized several drought-induced genes from peanut roots using a suppression subtractive hybridization (SSH) technique. Results: RNA was extracted from peanut roots subjected to a water stress treatment (45% field capacity) and from control plants (75% field capacity), and used to generate an SSH cDNA library. A total of 111 non-redundant sequences were obtained, with 80 unique transcripts showing homology to known genes and 31 clones with no similarity to either hypothetical or known proteins. GO and KEGG analyses of these differentially expressed ESTs indicated that drought-related responses in peanut could mainly be attributed to genes involved in cellular structure and metabolism. In addition, we examined the expression patterns of seven differentially expressed candidate genes using real-time reverse transcription-PCR (qRT-PCR) and confirmed that all were up-regulated in roots in response to drought stress, but to differing extents. Conclusions: We successfully constructed an SSH cDNA library in peanut roots and identified several drought-related genes. Our results serve as a foundation for future studies into the elucidation of the drought stress response mechanisms of peanut.

The present work describes the development of silk fibroin (SF)/chitosan (CS)-based porous composite anal fistula scaffold (SCAFS) with anti-inflammatory and healing functions. The SCAFS comprises an inner layer made from degummed silk fiber using a vertical braiding machine, and an outer layer created by freeze-drying a mixture of short SF fibers and curcumin (CUR)/5-aminosalicylic acid (5-ASA) loaded SF/CS solution. Results revealed that the SCAFS has high porosity of 42.4 %, remarkable water absorption rate of 370.5 %, robust dry/wet compression resistance of 12.28 ± 2.61 N/3.08 ± 0.43 N. The in vitro & in vivo biocompatibility and anti-inflammatory effect of SCAFS were further examined. The expression of pro-inflammatory cytokine TNF-α, anti-inflammatory cytokine IL-10, CD31 and CD68 was determined by immunohistochemistry (IHC) staining, H&E staining, Immunofluorescence (IF) staining and Masson assay. The results showed that the scaffolds possess a sustainable drug release above 400 h, better biocompatibility and anti-inflammatory effect than the control groups (p < 0.05). Thus, the SCAFS has potential application in the treatment of Crohn's disease., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: To evaluate the evolution and challenges of China's post-acute care (PAC) system over the past 20 years and suggest actionable policy recommendations for its improvement., Design: A retrospective review of policies and initiatives aimed at PAC system development, analyzed alongside unsolved challenges in light of global PAC practices, informed by literature reviews and collaborative discussion., Setting and Participants: PAC in China involves diverse settings such as general hospitals, inpatient rehabilitation centers, skilled nursing facilities, community health centers, and homes. The patients are mainly those discharged from acute hospitals with functional impairment and in need of continuous care., Method: An extensive search of government policy documents, statistical sources, peer-reviewed studies, and the gray literature. The research team conducted literature reviews and discussions regularly to shape the findings., Results: China has strengthened its PAC system through improved rehabilitation and nursing infrastructure, establishment of tiered rehabilitation networks, and adoption of innovative payment methods. However, challenges persist, including a lack of clinical consensus, resource constraints in PAC facilities and among professionals, the need for integrated care coordination, and the unification of PAC assessment tools and payment mechanisms., Conclusions and Implications: Although China has made substantial progress in its PAC system over 2 decades, continued efforts are needed to address its lingering challenges. Elevating awareness of PAC's significance and instituting policy adjustments targeting these challenges are essential for the system's optimization., Competing Interests: Disclosure The authors declare no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

In algae-bacteria symbiotic wastewater treatment, the excellent settling performance of algae-bacteria aggregates is critical for biomass separation and recovery. Here, the composition of extracellular polymeric substances (EPS), microbial profiles, and functional genes of algae-bacteria aggregates were investigated at different solid retention times (SRTs) (10, 20, and 40 d) during partial nitrification in photo sequencing bioreactors (PSBRs). Results showed that SRTs greatly influenced the nitrogen transformation and the formation and morphological structure of algae-bacteria aggregates. The highest nitrite accumulation, the largest particle size (~1.54 mm) and the best settling performance were observed for the algae-bacteria aggregates in the PSBR with an SRT of 10 d, where the abundant occurrence of filamentous cyanobacteria with the highest ratio of chlorophyll a/b and the lowest EPS amount with the highest protein-to-polysaccharide ratio were observed. In particular, the EPS at 10 d of SRT contained a higher amount of protein-related hydrophobic groups and a lower ratio of α-helix/(β-sheet + random coil), indicating a looser protein structure, which might facilitate the formation and stabilization of algae-bacteria aggregates. Moreover, algal-bacterial aggregation greatly depended on the composition and evolution of filamentous cyanobacteria (unclassified &#95;o&#95;&#95;Oscillatoriales and Phormidium accounted for 56.29 % of the identified algae at SRT 10 d). The metagenomic analysis further revealed that functional genes related to amino acid metabolism (e.g., genes of phenylalanine, tyrosine, and tryptophan biosynthesis) were expressed at high levels within 10 d of SRT. Overall, this study demonstrates the influence of EPS structures and filamentous cyanobacteria on algae-bacteria aggregation and reveals the biological mechanisms driving photogranule structure and function., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Background: Excessive copper (Cu) has risky effect on insulin resistance (IR), oxidative stress and inflammation. Instead, some studies reported serum Cu to be protective for non-alcoholic fatty liver disease (NAFLD). The aim of this study was to reevaluate the evidence for a potential risky correlation of serum Cu to NAFLD in large-scale and non-institutionalized American subjects., Methods: A cross-sectional study of 3211 subjects was from the National Health and Nutrition Examination Survey (NHANES). Logistic regression and cubic spline-based curve-fitting analyses were used to estimate the independent risky effect of Cu to hepatic steatosis index (HSI), US fatty liver index (USFLI) and NAFLD and their dose-effect relationship. Moreover, this association was analyzed in stratification of HOMA-IR, Metabolic syndrome (MetS) and severity of NAFLD, besides age and gender., Results: The average level of serum Cu was 18.67 μmol/L and the prevalence of NAFLD was 54.53% and 32.60%, respectively defined by HSI and USFLI. Generally, the level of Cu was higher in females than males. Serum Cu was positively associated with higher HSI, USFLI index and risk of NAFLD. In fully adjusted models, compared with the lowest quartile, the risk of NAFLD increased 97% in the highest quartile of Cu. Interestingly, stratified analysis showed that the risky effect of Cu to NAFLD was more prominent in the middle-aged, females and subjects with improved status of IR (lower HOMA-IR and non-Mets) compared with their counterparts. Moreover, we further found that circulating copper was correlated to severity of NAFLD only in males., Conclusion: Excess serum Cu is significantly associated with risk of NAFLD, which is prominent in females, middle-aged and subjects with improved status of IR, and seems to be related to the severity of NAFLD, additionally. It is necessary to be cautious of the toxic effect of Cu and prospective cohort and mechanism studies are needed to verify the causal effect of Cu to NAFLD., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

In order to investigate the pollution characteristics of size-segregated particles and metal elements (MEs) after the Chinese Air Pollution Prevention Action Plan was released in 2013, an intensive field campaign was conducted in the suburban area of Chaoyang District, Beijing in winter 2016. The size distributions of particle mass concentrations were bimodal, with the first peak in the fine fraction (0.4-2.1 µm) and the second peak in the coarse fraction (3.3-5.8 µm). Moreover, the proportion of fine particles increased and the proportion of coarse particles decreased as the pollution level was more elevated. It was found that the composition of coarse particles is as important as that of fine particles when pollution of aerosol metals in the atmosphere in 2016 were compared to 2013. In addition, according to the size distribution characteristics, 23 MEs were divided into three groups: (a) Fe, Co, Sr, Al, Ti, Ba, and U, which concentrated in coarse mode; (b) Zn, As, Cd, Tl, and Pb, which concentrated in fine mode; and (c) Na, K, Be, V, Cr, Mn, Ni, Cu, Mo, Ag, and Sn, showing bimodal distribution. Under clean air, slight pollution and moderate pollution conditions, most elements maintained their original size distributions, while under severe pollution, the unimodal distributions of most MEs became bimodal distributions. The factors analysis combined with size distributions indicated that Na, Zn, Mo, Ag, Cd, and Tl, showing the moderate to severe contamination on environment, were significantly influenced by diffuse regional emissions or anthropogenic source emissions (vehicle exhaust emissions and combustion process). The environmental risk assessment revealed that the heavy metal loading in the atmospheric particles collected had a high potential for ecological risk to the environment during sampling period because of the high contribution of Cd, Tl, Zn and Pb., (Copyright © 2021. Published by Elsevier Inc.)

Context: The annual consumption of opioid analgesics in the U.S. was more than 10 times the world average, whereas that in China was at a moderate level within Asia but much lower than the worldwide average. The opposite situations of opioid use in the U.S. and China revealed totally different problems in the developed versus developing world, that is, overuse versus underuse of opioids., Objectives: This study analyzed the clinical consumption, estimated the needs of pain treatment, and evaluated the adequacy of opioid analgesic consumption in mainland China and its seven regions., Methods: A retrospective analysis of the national and regional consumption of opioid analgesics in mainland China during 2006-2016 was conducted. The adequacy of consumption measure was used to gauge the overall adequacy of opioid analgesic consumption in morphine equivalents (MEs) for the treatment of moderate-to-severe pain in mainland China and compared with international data. Annual per capita consumption was adopted to measure the clinical consumption of opioid analgesics in MEs at a national level and across seven regions of mainland China. Needs of morphine for cancer pain treatment in mainland China and in its seven regions were estimated and compared with the clinical consumption of opioid analgesics in MEs., Results: The adequacy of consumption measure of mainland China ranged from 0.0041 to 0.0088 during 2006-2016, which was less than 1% of that in the reference countries. The poor North East region had only 10.85% of the cancer pain morphine needs fulfilled. The highest fulfillment rate was 36.02% in rich Southern China, which was 25.9% at the national level., Conclusion: The clinical consumption of opioid analgesics for the treatment of moderate-to-severe pain in mainland China was far below the international level. The annual per capita of clinical consumption was lower, and the adequacy of cancer pain treatment was poorer in less developed areas. All these findings call for actions to strengthen pain management., (Copyright © 2019 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

White light-emitting diodes (WLEDs) are of scientific significance in terms of their wide applications, and few uminescent materials based on white-light-emitting polyoxometalate (POM) derivatives have been reported till now. Herein, a series of organic chromophores modified POM derivatives [N(CH 3 ) 4 ] 3 K 2 Ln(C 7 H 5 O 2 )(H 2 O) 2 (α-PW 11 O 39 )]·11H 2 O (Ln 3+  = Eu 3+ (1), Tb 3+ (2), Tm 3+ (3), Lu 3+ (4)) and multicenter-Ln analogues [N(CH 3 ) 4 ] 3 K 2 Eu x Tb y Tm 1-x-y (C 7 H 5 O 2 )(H 2 O) 2 (α-PW 11 O 39 )·11H 2 O (5-11) were synthesized successfully and were characterized by various physico-chemical analysis. The investigations indicate the white-light-emitting behavior can be well tuned by adjusting the molar ratio of Eu 3+ /Tb 3+ /Tm 3+  = 0.06:0.10:0.84 in 9. The energy transfer process from organic benzoic and POM ligands to Eu 3+ , Tb 3+ and Tm 3+ emitting centers were detected through time-resolved emission spectroscopy (TRES) and the comparison of excitation of single-, double-, treble-Ln 3+ mixed, indicating the energy can transfer from the photoexcitation O → M LMCT state of POM components and π → π* transition of organic ligand to sensitize the emissions of Ln 3+ ions via intramolecular energy transition mechanism. The energy transfer between Eu 3+ and Tb 3+ , Tm 3+ and Eu 3+ , Tm 3+ and Tb 3+ ions also have been recorded and carefully studied by TRES and variations of Tm 3+ luminescence lifetime in this context, and the results show a low-effectively process of energy transfer between Tm 3+ /Eu 3+ , Tm 3+ /Tb 3+ ions and a relatively good energy transfer efficiency between Eu 3+ /Tb 3+ ions., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Chemical constitution and construction of functional sites play a crucial part in the chromatographic behavior of stationary phases. We present novel polymeric anion exchangers covalently grafted with linear quaternary ammonium polyelectrolytes via simple one-step epoxy-amine polymerization. In separation of various anionic analytes, the newly developed anion exchangers showed high efficiency (e.g., >30,000 plates m -1 for chloride with hydroxide elution) and peculiar chromatographic behavior as compared to previously reported hyperbranched phases. By adopting different amines as the building unite of linear polyelectrolytes, the two types of model anion exchangers displayed segregated selectivity which in our opinion is associated with charge density, hydrophilicity and low cross-linking of the functionalities., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: The role of adjuvant radiotherapy (ART) in patients with World Health Organization Grade II atypical meningiomas (AMs) remains controversial., Methods: We retrospectively reviewed 149 patients with newly diagnosed resected AMs from 2000 to 2012. Gross total resection (GTR) was defined as Simpson Grades I-III and subtotal resection (STR) as Grades IV and V. Kaplan-Meier analyses of local control (LC), progression-free survival (PFS), and overall survival were performed with the log-rank test, and risk factors for progression/recurrence (P/R) were analyzed with multivariate Cox regression., Results: Median follow-up was 74.2 months. GTR was achieved in 98 patients and STR in 51 patients. Fifty-three (35%) patients received ART. Overall, 46 patients (31%) experienced P/R with a median time to P/R of 32.4 months. ART was associated with a trend toward improved PFS (P = 0.0669) in the GTR subset but significantly improved LC (P = 0.0183) and PFS (P = 0.0034) in the STR subset. Age, tumor size, and STR were significant risk factors for worse PFS, whereas receiving ART was associated with improved PFS on multivariate analyses. Thirty-nine of the 46 progressive/recurrent patients underwent salvage therapy with only 22 patients experiencing long-term control. Five patients experienced transformation to World Health Organization Grade III malignant meningioma., Conclusions: Patients who undergo STR for newly diagnosed AM should receive ART based on improvements in LC and PFS. GTR patients should be considered for ART, but active surveillance is a reasonable management approach with the recognition that progressive/recurrent disease can act aggressively. Prospective, randomized trials are currently underway to evaluate the role of ART., (Published by Elsevier Inc.)

The covalent modification of polymeric particles has been a challenge due to their chemical inertness. Herein we describe a facile and neat method via thiol-ene reaction to immobilize cysteamine/cysteine onto allylmethacrylate-divinylbenzene (AMA-DVB) and ethylvinylbenzene-divinylbenzene (EVB-DVB). The introduced functionalities were verified by elementary analysis and scanning electron microscope coupled with energy dispersive spectroscopy. This modification enabled the further grafting of hyperbranched condensation polymers (HBCPs), which converted the particles into anion exchangers. The anion exchangers demonstrated good separation with carbonate/bicarbonate eluents and hydroxide eluents for suppressed anion exchange chromatography. In the case of a 3-layered anion exchanger, simultaneous separation of nine model anions was achieved by isocratic elution in 17 min with efficiencies up to 16,100 plates m -1 . High stability and dependable durability was exhibited in long-term tests., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Carbonaceous stationary phases have gained much attention for their peculiar selectivity and robustness. Herein we report the fabrication and application of a graphene-coated polymeric stationary phase for anion exchange chromatography. The graphene-coated particles were fabricated by a facile evaporation-reduction method. These hydrophilic particles were proven appropriate substrates for grafting of hyperbranched condensation polymers (HBCPs) to make pellicular anion exchangers. The new phase was characterized by zeta potentials, Fourier transform infrared spectroscopy, thermogravimetry and scanning electron microscope. Frontal displacement chromatography showed that the capacities of the anion exchangers were tuned by both graphene amount and HBCPs layer count. The chromatographic performance of graphene-coated anion exchangers was demonstrated with separation of inorganic anions, organic acids, carbohydrates and amino acids. Good reproducibility was obtained by consecutive injections, indicating high chemical stability of the coating., (Copyright © 2017. Published by Elsevier B.V.)

Background: Previous studies showed improvement in heart function by injecting bone marrow mesenchymal stem cells (BMSCs) after AMI. Emerging evidence suggested that both the number and function of BMSCs decline with ageing. We designed a randomized, controlled trial to further investigate the safety and efficacy of this treatment., Methods: Patients with ST-elevation AMI undergoing successful reperfusion treatment within 12 hours were randomly assigned to receive an intracoronary infusion of BMSCs (n=21) or standard medical treatment (n=22) (the numbers of patients were limited because of the complication of coronary artery obstruction)., Results: There is a closely positive correlation of the number and function of BMSCs vs. the cardiac function reflected by LVEF at baseline (r=0.679, P=0.001) and at 12-month follow-up (r=0.477, P=0.039). Six months after cell administration, myocardial viability within the infarct area by 18-FDG SPECT was improved in both groups compared with baseline, but no significant difference in the BMSCs compared with control groups (4.0±0.4% 95%CI 3.1-4.9 vs. 3.2±0.5% 95%CI 2.1-4.3, P=0.237). 99mTc-sestamibi SPECT demonstrated that myocardial perfusion within the infarct area in the BMSCs did not differ from the control group (4.4±0.5% 95%CI 3.2-5.5 vs. 3.9±0.6% 95%CI 2.6-5.2, P=0.594). Similarly, LVEF after 12 and 24 months follow-up did not show any difference between the two groups. In the BMSCs group, one patient suffered a serious complication of coronary artery occlusion during the BMSCs injection procedure., Conclusions: The clinical benefits of intracoronary injection of autologous BMSCs in acute STEMI patients need further investigation and reevaluation., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Zinc ribbon domain-containing 1 (ZNRD1), a transcription-associated gene, was recently found to be downregulated in human gastric cancer tissues as compared to the matched adjacent nonneoplastic tissues. In this study, we constructed the siRNA eukaryotic expression vectors of ZNRD1 and transfected them into normal gastric epithelial cells (GES-1). We also introduced the ZNRD1 gene into gastric cancer cells that do (SGC7901) and do not (AGS) express ZNRD1 endogenously. GES-1 cells stably transfected with the ZNRD1-RNAi were found to exhibit significantly quicker proliferation than empty vector transfectants. AGS cells stably transfected with the ZNRD1 cDNA exhibited significantly decreased growth rate as compared to control vector transfectants, whereas SGC7901 cells did not. Furthermore, ZNRD1 suppresses growth of AGS cells in soft agar and tumor formation in athymic nude mice. This study clearly demonstrates that ZNRD1 may play an important role in the control of human gastric cancer development by regulating cell proliferation. These results provide new insights into the function of ZNRD1 and further validate ZNRD1 as a potential therapeutic target in gastric cancer.