Search

Abstract Background N6-Methyladenosine (m6A) methylation, a common form of RNA modification, play an important role in the pathogenesis of various diseases and in the ontogeny of organisms. Nevertheless, the precise function of m6A methylation in photoaging remains unknown. Objectives This study aims to investigate the biological role and underlying mechanism of m6A methylation in photoaging. Methods m6A dot blot, Real-time quantitative PCR (RT-qPCR), western blot and immunohistochemical (IHC) assays were employed to detect the m6A level and specific m6A methylase in ultraviolet ray (UVR)-induced photoaging tissue. The profile of m6A-tagged mRNA was identified by methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA-seq analysis. Finally, we investigated the regulatory mechanism of KIAA1429 by MeRIP-qPCR, RNA knockdown and immunofluorescence assay. Results m6A levels were increased in photoaging and were closely associated with the upregulation of KIAA1429 expression. 1331 differentially m6A methylated genes were identified in the UVR group compared with the control group, of which 1192 (90%) were hypermethylated. Gene ontology analysis showed that genes with m6A hypermethylation and mRNA downregulation were mainly involved in extracellular matrix metabolism and collagen metabolism-related processes. Furthermore, KIAA1429 knockdown abolished the downregulation of TGF-bRII and upregulation of MMP1 in UVR-irradiated human dermal fibroblasts (HDFs). Mechanically, we identified MFAP4 as a target of KIAA1429-mediated m6A modification and KIAA1429 might suppress collagen synthesis through an m6A-MFAP4-mediated process. Conclusions The increased expression of KIAA1429 hinders collagen synthesis during UVR-induced photoaging, suggesting that KIAA1429 represents a potential candidate for targeted therapy to mitigate UVR-driven photoaging.

Abstract The family of coinage-metal-based cyclic trinuclear complexes exhibits abundant photophysical properties, promising for diverse applications. However, their utility in biochemistry is often hindered by large particle size and strong hydrophobicity. Meanwhile, the investigation into multi-photon excited luminescence within this family remained undocumented, limiting their potential in bio-imaging. Herein, we unveil the multi-photon excited luminescent properties of pyrazolate-based trinuclear gold(I) clusters, facilitated by excimeric gold(I)···gold(I) interactions, revealing a nonlinear optical phenomenon within this family. Furthermore, to address issues of poor biocompatibility, we employ electrospinning coupled with hydroxypropyl-beta-cyclodextrin as the matrix to fabricate a flexible, durable, transparent, and red emissive film with a photoluminescence quantum yield as high as 88.3%. This strategy not only produces the film with sufficient hydrophilicity and stability, but also achieves the downsizing of trinuclear gold(I) clusters from microscale to nanoscale. Following the instantaneous dissolution of the film in the media, the released trinuclear gold(I) nanoparticles have illuminated cells and bacteria through a real-time, non-toxic, multi-photon bio-imaging approach. This achievement offers a fresh approach for utilizing coinage-metal-based cyclic trinuclear complexes in biochemical fields.

IntroductionGeneralized anxiety disorder (GAD) is a common mental disorder that often begins in adolescence or early adulthood and is characterized by widespread and persistent anxiety. Partial sleep deprivation (PSD) is an important risk factor for GAD development and a common comorbidity. Adolescence is a period of rapid brain and nervous system development, and during this time, the occurrence of GAD can lead to neurocognitive deficits, such as impaired attention, cognitive control, and attention bias, that significantly affect cognitive function. However, relatively little research has been conducted on GAD comorbid with PSD in early adulthood compared with other psychiatric disorders. Clinical studies have demonstrated the effectiveness of acupuncture in treating GAD and sleep disorders, but the mechanism of how acupuncture modulates neurocognitive processing in patients with GAD comorbid with PSD has not been clarified.Methods/designIn this randomized clinical trial, a total of 56 participants diagnosed with GAD comorbid with naturally occurring PSD and 28 healthy controls (HCs) will be recruited. The participants diagnosed with GAD comorbid with PSD will be randomly assigned to either the acupuncture group or the sham acupuncture group at a 1:1 ratio. The primary outcome measure is the Hamilton Anxiety Rating Scale (HAMA). Secondary outcome measures are the Sleep Deprivation Index (SDI), the Self-Assessment Scale for Anxiety (SAS), the Epworth Sleepiness Scale (ESS), and the State-Trait Anxiety Inventory (STAI). Additionally, three psychological paradigms (the attentional network test, psychomotor vigilance test, and emotional face Go/No-go) and event-related potential (ERP) data. Healthy volunteers will not undergo acupuncture but will instead participate in baseline assessments for the scales, mental paradigms, and ERP data. Acupuncture and sham acupuncture interventions will be conducted for 30 min, three times a week, over a 2-week period. Evaluations will be performed at zero weeks (baseline), 1 week, and 2 weeks, with the data enumerator, outcome assessor, and participant blinded to the treatment assignment.DiscussionThis study contributes to the exploration of the effects of acupuncture on improving anxiety symptoms and cognitive functions in individuals with comorbid GAD and PSD.Trial registrationClinicalTrials.gov, ChiCTR2400082221. Registered March 25, 2024.

IntroductionPost-stroke depression (PSD) is the most common complication following a stroke, significantly hindering recovery and rehabilitation in affected patients. Despite its prevalence, the pathogenesis of PSD remains poorly understood. Electroacupuncture (EA) has shown antidepressant effects, yet its neuroprotective properties are not well defined. Ferroptosis, a recently identified form of cell death, is implicated in the pathological processes of stroke and is associated with the development of depression-like behaviors. So we aimed to investigate whether PSD induces ferroptosis, identify potential therapeutic targets within these pathways, and elucidate the underlying mechanisms in this study.MethodsMale Sprague-Dawley rats were subjected to middle carotid artery occlusion and chronic unpredictable mild stress to model PSD. To explore the role of ferroptosis in the effects of EA, the ferroptosis inducer erastin was administered into the rats’ lateral ventricles, followed by 14 days of EA treatment, with sessions lasting 30 minutes per day. The Zea-Longa score was used to assess neurological deficits, while the sucrose preference test, elevated plus maze test, and open-field test were employed to evaluate depression-like behaviors in the rats. Hematoxylin-eosin, Nissl, and Perl’s staining were used to observe the morphological changes and iron deposition in the prefrontal neurons. Transmission electron microscopy provided detailed observations of mitochondrial morphological changes in neurons. We utilized activity assay kits, enzyme-linked immunosorbent assay (ELISA), and Western blotting to explore potential molecular mechanisms underlying the effects of EA.ResultsEA can reduce neurological deficits and enhance the spontaneous activity and exploration behavior of rats. In addition, EA could inhibit prefrontal cortex neuronal ferroptosis by reducing iron deposition, decreasing lipid peroxidation, and enhancing antioxidation.DiscussionEA improved depression-like behaviors, mitigated mitochondrial damage, and inhibited ferroptosis in prefrontal cortex neurons. Notably, the administration of erastin further enhanced these effects. In conclusion, EA appears to improve PSD by inhibiting ferroptosis in the prefrontal cortex.

Background Symptom networks offer a theoretical basis for developing personalised and precise symptom management strategies. However, symptom networks in lymphoma patients during chemotherapy have been rarely reported. This study intends to establish contemporaneous symptom networks in lymphoma patients during chemotherapy and explore the centrality indices and density in these symptom networks.Methods and analysis This is a single-centre prospective cross-sectional study. A total of 315 lymphoma patients admitted to the Lymphoma Department of Shanxi Bethune Hospital since 1 June 2024 will be selected as the study subjects. The patient-reported outcome measures of General Data Questionnaire and Lymphoma Symptom Assessment Scale will be assessed. R package will be used to construct a contemporaneous symptom network, explore the relationship between core and analysed symptoms and analyse the predictive role of network density on patient prognosis.Ethics and dissemination This study adheres to the principles of the Declaration of Helsinki and relevant ethical guidelines. Ethical approval has been obtained from Shanxi Bethune Hospital Ethics Committee (approval number: YXLL-2023-186). The final outcomes will be published in a peer-reviewed journal and disseminated through a conference.

Background: Oxidative stress and cellular senescence (OSCS) have great impacts on the occurrence and progression of triple-negative breast cancer (TNBC). This study was intended to construct a prognostic model based on oxidative stress and cellular senescence related difference expression genes (OSCSRDEGs) for TNBC. Methods: The Cancer Genome Atlas (TCGA) databases and two Gene Expression Omnibus (GEO) databases were used to identify OSCSRDEGs. The relationship between OSCSRDEGs and immune infiltration was examined using single-sample gene-set enrichment analysis (ssGSEA), ESTIMATE, and the CIBERSORT algorithm. Least absolute shrinkage and selection operator (LASSO) regression analyses, Cox regression and Kaplan-Meier analysis were employed to construct a prognostic model. Receiver operating characteristic (ROC) curves, nomograms, and decision curve analysis (DCA) were used to evaluate the prognostic efficacy. Gene Set Enrichment Analysis (GSEA) Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) were utilized to explore the potential functions and mechanism. Results: A comprehensive analysis identified a total of 27 OSCSRDEGs, out of which 15 genes selected for development of a prognostic model. A high degree of statistical significance was observed for the riskscores derived from this model to accurately predict TNBC Overall survival. The decision curve analysis (DCA) and ROC curve analysis further confirmed the superior accuracy of the OSCSRDEGs prognostic model in predicting efficacy. Notably, the nomogram analysis highlighted that DMD exhibited the highest utility within the model. In comparison between high and low OSCScore groups, the infiltration abundance of immune cells was statistically different in the TCGA-TNBC dataset. Conclusion: These studies have effectively identified four essential OSCSRDEGs (CFI, DMD, NDRG2, and NRP1) and meticulously developed an OSCS-associated prognostic model for individuals diagnosed with TNBC. These discoveries have the potential to significantly contribute to the comprehension of the involvement of OSCS in TNBC.

Objective: To explore the effects and possible mechanisms of the drug pair Cornus officinalis and Radix achyranthis bidentatae (SYR-NX) on improving hypertensive kidney damage. Method: SYR-NX, a formulation of Cornus officinalis and Radix Achyranthis Bidentatae with a dose ratio 1:2.5, was used in this experiment. We investigated the effects of SYR-NX on spontaneously hypertensive rats (SHR) fed with a high-salt diet and Human Kidney-2 (HK2) cells exposed to hypoxia. After 8 weeks of treatment with SYR-NX, blood pressure was tested, and β 2-Microglobulin(β2-MG), blood creatinine (S-cr), endothelial nitric oxide synthase (eNOS), nicotinamide adenine dinucleotide phosphate (NADPH), M2 pyruvate kinase (PKM2), adenosine triphosphate (ATP), pyruvate, lactate, connective tissue growth factor (CTGF) and tumor necrosis factor-α (TNF-α)were measured. HK2 cells pre-treated with SYR-NX were cultured in a three-gas hypoxic incubator chamber (5 % CO2, 1 % O2, 94 % N2) for 12 h, and then eNOS, PKM2, NADPH, ATP, pyruvate, lactate, CTGF and TNF-α were assessed. Results: SYR-NX significantly reduced SBP, DBP, β2-MG, S-cr, PKM2, pyruvate, lactate, CTGF and TNF-α, and increased eNOS, NADPH, and ATP. Conclusion: SYR-NX can regulate metabolic reprogramming through eNOS and improves hypertensive kidney injury.

ObjectiveTo examine the dose–response relationship between specific types of exercise for alleviating Timed up and Go (TUG) in Parkinson’s disease PD.DesignSystematic review and Bayesian network meta-analysis.Data sourcesPubMed, Medline, Embase, PsycINFO, Cochrane Library, and Web of Science were searched from inception until February 5th, 2024.Study analysisData analysis was conducted using R software with the MBNMA package. Effect sizes of outcome indicators were expressed as mean deviation (MD) and 95% confidence intervals (95% CrI). The risk of bias in the network was evaluated independently by two reviewers using ROB2.ResultsA total of 73 studies involving 3,354 PD patients. The text discusses dose–response relationships in improving TUG performance among PD patients across various exercise types. Notably, Aquatic (AQE), Mix Exercise (Mul_C), Sensory Exercise (SE), and Resistance Training (RT) demonstrate effective dose ranges, with AQE optimal at 1500 METs-min/week (MD: −8.359, 95% CI: −1.398 to −2.648), Mul_C at 1000 METs-min/week (MD: −4.551, 95% CI: −8.083 to −0.946), SE at 1200 METs-min/week (MD: −5.145, 95% CI: −9.643 to −0.472), and RT at 610 METs-min/week (MD: −2.187, 95% CI: −3.161 to −1.278), respectively. However, no effective doses are found for Aerobic Exercise (AE), Balance Gait Training (BGT), Dance, and Treadmill Training (TT). Mind–body exercise (MBE) shows promise with an effective range of 130 to 750 METs-min/week and an optimal dose of 750 METs-min/week (MD: −2.822, 95% CI: −4.604 to −0.996). According to the GRADE system, the included studies’ overall quality of the evidence was identified moderate level.ConclusionThis study identifies specific exercise modalities and dosages that significantly enhance TUG performance in PD patients. AQE emerges as the most effective modality, with an optimal dosage of 1,500 METs-min/week. MBE shows significant benefits at lower dosages, catering to patients with varying exercise capacities. RT exhibits a nuanced “U-shaped” dose–response relationship, suggesting an optimal range balancing efficacy and the risk of overtraining. These findings advocate for tailored exercise programs in PD management, emphasizing personalized prescriptions to maximize outcomes.Systematic Review Registration: International Prospective Register of Systematic Reviews (PROSPERO) (CRD42024506968).

BackgroundExtensive research has been conducted on the correlation between adipose tissue and the risk of malignant lymphoma. Despite numerous observational studies exploring this connection, uncertainty remains regarding a causal relationship between adipose tissue and malignant lymphoma.MethodsThe increase or decrease in adipose tissue was represented by the height of BMI. The BMI and malignant lymphoma genome-wide association studies (GWAS) used a summary dataset from the OPEN GWAS website. Single-nucleotide polymorphisms (SNPs) that met the criteria of P 0.8 were identified, while palindromic and outlier SNPs were excluded. Mendelian randomization (MR) analysis used five methods, including inverse-variance weighted (IVW) model, weighted median (WM), MR-Egger, simple mode, and weighted mode. Sensitivity assessments included Cochran’s Q test, MR-Egger intercept test, and leave-one-out analysis. Participants randomly selected by the National Center for Health Statistics (NHANSE) and newly diagnosed HL patients at Fujian Medical University Union Hospital were used for external validation.ResultsThe results of the MR analysis strongly supported the causal link between BMI and Hodgkin’s lymphoma (HL). The research demonstrated that individuals with lower BMI face a significantly increased risk of developing HL, with a 91.65% higher risk (ORIVW = 0.0835, 95% CI 0.0147 – 0.4733, P = 0.005). No signs of horizontal or directional pleiotropy were observed in the MR studies. The validation results aligned with the results from the MR analysis (OR = 0.871, 95% CI 0.826 – 0.918, P< 0.001). And there was no causal relationship between BMI and non-Hodgkin’s lymphoma (NHL).ConclusionsThe MR analysis study demonstrated a direct correlation between lower BMI and HL. This suggested that a decrease in adipose tissue increases the risk of developing HL. Nevertheless, further research is essential to grasp the underlying mechanism of this causal association comprehensively.

Background Cell division cycle protein 45 (CDC45) has been demonstrated to play vital roles in the progression of various malignancies. However, the clinical significance of CDC45 in gastric cancer (GC) remains unreported. Method In this study, we employed the TCGA database and the TCGA & GTEx dataset to compare the mRNA expression levels of CDC45 between gastric cancer tissues and adjacent or normal tissues (p < 0.05 was considered statistically significant), which was further validated in multiple datasets including GSE13911, GSE29272, GSE118916, GSE66229, as well as RT-qPCR. Furthermore, we harnessed the Human Protein Atlas (HPA) to evaluate the protein expression of CDC45, which was subsequently verified through immunohistochemistry (IHC). To ascertain the diagnostic utility of CDC45, receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC) were calculated in TCGA database, and further validated it in TCGA & GTEx and GSE66229 datasets. The Kaplan–Meier method was used to reveal the prognostic importance of CDC45 in The Cancer Genome Atlas (TCGA) database and authenticated through the GSE66229, GSE84433, and GSE84437 datasets. Through cBioPortal, we identified co-expressed genes of CDC45, and pursued enrichment analysis. Additionally, we availed gene set enrichment analysis (GSEA) to annotate the biological functions of CDC45. Results Differential expression analysis revealed that CDC45 was significantly upregulated at both the mRNA and protein levels in GC (all p < 0.05). Remarkably, CDC45 emerged as a promising prognostic indicator and a novel diagnostic biomarker for GC. In a comprehensive the drug susceptibility analysis, we found that patients with high expression of CDC45 had high sensitivity to various chemotherapeutic agents, among which 5-fluorouracil, docetaxel, cisplatin, and elesclomol were most evident. Furthermore, our findings suggested a plausible association between CDC45 and immune cell infiltration. Enrichment analysis revealed that CDC45 and its associated genes may play crucial roles in muscle biofunction, whereas GSEA demonstrated significant enrichment of gene sets pertaining to G protein-coupled receptor ligand binding and G alpha (i) signaling events. Conclusion Our study elucidates that upregulation of CDC45 is intricately associated with immune cell infiltration and holds promising potential as a favorable prognostic marker and a novel diagnostic biomarker for GC.

Abstract Background Effective pain management is closely related to nurses’ knowledge, attitudes and empathy regarding pain. Nursing educators and managers should understand the relationship between nurses’ pain management knowledge, attitudes and empathy level, and take targeted measures accordingly. Currently, there is limited study exploring the relationship between pain empathy and pain knowledge and attitudes among nurses in North China. Objectives The purpose of this study was to investigate the level of nurses’ pain management knowledge and attitudes and pain empathy, to analyze the factors influencing pain empathy, and to explore the relationship between these two variables. Design This study was a quantitative, descriptive-correlation design. Setting and participants The study population was registered nurses in North China, the sample included 177 registered nurses in North China. Methods Data were collected with the “General data questionnaire”, “Knowledge and attitudes survey regarding pain” (KASRP) and the “Empathy for pain scale” (EPS) via Wechat mini program “Questionnaire Star”. Results The 177 registered nurses completed the survey. The averege correct rate for KASRP was (51.94 ± 9.44)%, and none of the respondents achieved a percentage score of >80%. The mean score for pain empathy was (2.78 ± 0.78), the empathy reactions dimension was (2.99 ± 0.77), and the body and mind discomfort dimension was (2.71 ± 0.80). The results of multiple stepwise linear regression showed that whether they had received empathy training, whether they had greater trauma or severe pain and whether they had negative emotions were independent influencing factors for EPS scores. Pearson correlation analysis showed that KASRP scores were positively correlated with EPS scores (r = 0.242, P

Abstract Background Exploration of the relationship between individual work immersion and perceived stress is critical for clinical nurses’ effective psychological interventions and human resource management, as well as to alleviate nursing staff shortages. In order to further dissect the influencing factors of perceived stress among nursing staff, our study introduces the concepts of perfectionism and social connectedness to analyze the specific pathways that influence perceived stress in terms of an individual’s intrinsic and external personality traits. This study provides relevant recommendations for the development of stress management measures for nursing staff. Methods This was a cross-sectional survey. 993 registered clinical nurses were included from four hospitals in Guangzhou through a convenience sampling method. Clinical nurses’ work immersion, perceived stress, perfectionism, and social connectedness were investigated using questionnaires based on latent profile analysis. The relationships between variables were analyzed using t-tests, analysis of variance, Pearson’s correlation analysis, latent profile analysis, and moderated mediation analysis. Results The results showed that (1) general influences on nurses’ perceived stress included only child, labor relationship, labor allowance, and family support; (2) nurses’ work immersion contained four subgroups: lowest (12.6%), medium-low (39.8%), medium-high (39.9%), and highest (7.7%); (3) positive and negative perfectionism played a mediating role between the association of work immersion and perceived stress; (4) social connectedness played a moderating role in the mediation model of perceived stress. Conclusions Work immersion, perfectionism, and social connectedness have an important impact on clinical nurses’ perceived stress. Nursing managers or leaders should pay attention to the differences of individual work immersion status, adopt reasonable stress management strategies, accurately identify positive perfectionist groups and strengthen the relationship between groups, so as to ensure the quality of nursing care, and reduce nursing turnover and alleviate the problem of staff shortage.

Specular highlight removal is a challenging task in the field of image enhancement, while it can significantly improve the quality of image in highlight regions. Recently, deep learning-based methods have been widely adopted in this task, demonstrating excellent performance by training on either massive paired data, wherein both the highlighted and highlight-free versions of the same image are available, or unpaired datasets where the one-to-one correspondence is inapplicable. However, it is difficult to obtain the corresponding highlight-free version of a highlight image, as the latter has already been produced under specific lighting conditions. In this paper, we propose a method for weakly supervised specular highlight removal that only requires highlight images. This method involves generating highlight-free images from highlight images with the guidance of masks estimated using non-negative matrix factorization (NMF). These highlight-free images are then fed consecutively into a series of modules derived from a Cycle Generative Adversarial Network (Cycle-GAN)-style network, namely the highlight generation, highlight removal, and reconstruction modules in sequential order. These modules are trained jointly, resulting in a highly effective highlight removal module during the verification. On the specular highlight image quadruples (SHIQ) and the LIME datasets, our method achieves an accuracy of 0.90 and a balance error rate (BER) of 8.6 on SHIQ, and an accuracy of 0.89 and a BER of 9.1 on LIME, outperforming existing methods and demonstrating its potential for improving image quality in various applications.

TiO2 nanotube (TNT) morphology is crucial for applications in a variety of fields. In this paper, response surface methodology (RSM) has been utilized to optimize the anodizing parameters i.e., electrolyte concentration (C), anodization voltage (V), and time (t) for morphology (e.g., nanotube diameter and length) of TNTs. Ethylene glycol (EG) based electrolyte has been used for anodization employing ammonium fluoride (NH4F) as a source of fluoride ion (F–) with 2.5 vol% H2O. Reliable regression models have been developed between the input variables and the corresponding responses, namely tube diameter and length with multiple regression coefficients of 0.9649 and 0.9253, respectively, revealing a trustworthy association between the actual and those predicted values using the quadratic model. The predicted values of C (0.31 wt%), V (38.44 V), and t (69.37 min) were found to be the optimum anodization condition preceding a TiO2 nanotubes diameter of 99.31 nm and length of 4572.64 nm. It was observed that the nanotubes diameter and length are more affected by anodizing voltage and time, and less sensitive to NH4F concentration. Therefore, RMS could be an appropriate technique to optimize anodizing parameters for producing TiO2 nanotubes with good morphology.

Abstract Background SCT510 is a recombinant humanized monoclonal antibody targeting vascular endothelial growth factor (VEGF), which is intended as a candidate biosimilar of bevacizumab that is approved for various metastatic cancers.Please confirm change in wording to match definition for VEGF belowYes. Objective This study aimed to compare the pharmacokinetics profiles, safety, and immunogenicity of SCT510 to bevacizumab (Avastin®) in healthy Chinese males. Methods This was a single-center, double-blind, parallel-group phase I study. A total of 84 participants were randomly assigned (1:1) to receive a single 3 mg/kg infusion of either SCT510 or bevacizumab and followed up for 99 days. Primary endpoints were area under the serum concentration–time curve from time 0 extrapolated to infinity (AUC0–∞), area under the serum concentration–time curve from time 0 to last quantifiable concentration (AUC0–t), and the maximum observed concentration (Cmax). Secondary endpoints included safety and immunogenicity.Kindly check and confirm the edit made in the article title.Yes. Results A total of 82 subjects completed the study. Geometric means ratios (GMR) for AUC0–∞, AUC0–t, and Cmax were 0.88, 0.89, and 0.97, respectively, for SCT510 versus bevacizumab (USA). The 90% confidence intervals for GMRs of AUC0–∞, AUC0–t, and Cmax were all within the prespecified criteria (80–125%). No adverse events (AEs) led to study termination, and no serious adverse events (SAEs) were reported. None of the anti-drug antibodies (ADAs) identified were found to be neutralizing antibodies (NAbs), and only one subject from the SCT510 group tested positive for the ADA at the day 99 visit. Conclusion This study demonstrated that the pharmacokinetics, safety, and immunogenicity of SCT510 were equivalent to bevacizumab (Avastin®). As a proposed biosimilar drug to bevacizumab, SCT510 was well tolerated in healthy Chinese males. Clinical Trials Registration NCT05113511.

Two experiments were conducted in this research. Experiment 1 investigated the spatial expression characteristics of calcium (Ca) and phosphorus (P) transporters in the duodenum, jejunum, and ileum of 21-day-old broilers provided with adequate nutrient feed. Experiment 2 evaluated the effects of dietary vitamin D3 (VD3) concentration (0, 125, 250, 500, 1,000, and 2,000 IU/kg) on growth performance, bone development, and gene expression levels of intestinal Ca and P transporters in 1–21-day-old broilers provided with the negative control diet without supplemental VD3. Results in experiment 1 showed that the mRNA levels of calcium-binding protein 28-kDa (CaBP-D28k), sodium-calcium exchanger 1 (NCX1), plasma membrane calcium ATPase 1b (PMCA1b), and IIb sodium-phosphate cotransporter (NaPi-IIb) were the highest in the broiler duodenum. By contrast, the mRNA levels of inorganic phosphate transporter 1 (PiT-1) and 2 (PiT-2) were the highest in the ileum. Results in experiment 2 showed that adding 125 IU/kg VD3 increased body weight gain (BWG), feed intake (FI), bone weight, and percentage and weight of Ca and P in the tibia and femur of 1–21-day-old broilers compared with the negative control diet (p < 0.05). The rise in dietary VD3 levels from 125 to 1,000 IU/kg further increased the BWG, FI, and weights of the bone, ash, Ca, and P (p < 0.05). No difference in growth rate and leg bone quality was noted in the broilers provided with 1,000 and 2,000 IU/kg VD3 (p > 0.05). Supplementation with 125–2,000 IU/kg VD3 increased the mRNA abundances of intestinal Ca and P transporters to varying degrees. The mRNA level of CaBP-D28k increased by 536, 1,161, and 28 folds in the duodenum, jejunum, and ileum, respectively, after adding 1,000 IU/kg VD3. The mRNA levels of other Ca and P transporters (PMCA1b, NCX1, NaPi-IIb, PiT-1, and PiT-2) increased by 0.57–1.74 folds by adding 1,000–2,000 IU/kg VD3. These data suggest that intestinal Ca and P transporters are mainly expressed in the duodenum of broilers. Moreover, the addition of VD3 stimulates the two mineral transporter transcription in broiler intestines.

As an important hydrological ecosystem component, the glacier basin has great significance for climate and environment, and it is also linked to regional water sustainability. In this paper, the sampling and isotope analysis of glacial ice, ice-melt water, river water (river midstream and river downstream), groundwater (spring), and precipitation were carried out in a hydrological year of the Mingyong Glacier basin, which is located at the Meili Snow Mountains, Southeastern Tibetan Plateau. At the same time, the hydrograph separation of the recharge sources of the lower mountain pass is studied. The results show that the range of δD, δ18O, and d-excess (deuterium excess) in natural water bodies are significantly different, and the precipitation is the most obvious. The high values of δD and δ18O in the water samples all appeared in spring and summer, and the low values appeared in autumn and winter, while glacial ice showed opposite trends. Meanwhile, the local meteoric water line (LMWL) of the Mingyong Glacier basin is δD = 8.04δ18O + 13.06. The End-Member Mixing Analysis (EMMA) was adopted to determine the sources proportion of river water (river downstream) according to the δD, δ18O, and d-excess ratio relationships. The results showed that the proportion of ice-melt water, groundwater, and precipitation in the ablation period was 80.6%, 17.2%, and 2.2% as well as 19.2%, 73.1%, and 7.7% in the accumulation period, respectively. Ice-melt water has a higher conversion recharge rate to groundwater and indirectly recharges river water, especially in nonmonsoon seasons. In other words, the main recharge source of river water in the lower reaches of the Mingyong Glacier basin during the ablation period is ice-melt water. In the accumulation period, the main recharge source of river water in the lower reaches of the Mingyong Glacier basin is groundwater, while nearly half of the recharge of groundwater comes from ice-melt water. Therefore, regardless of the ablation period or the accumulation period, ice-melt water is sustainable and important to this region.

Aberrant glycolytic reprogramming is involved in lung cancer progression by promoting the proliferation of non-small cell lung cancer cells. Paeonol, as a traditional Chinese medicine, plays a critical role in multiple cancer cell proliferation and inflammation. Acyl-CoA dehydrogenase (ACADM) is involved in the development of metabolic diseases. N6-methyladenosine (m6A) modification is important for the regulation of messenger RNA stability, splicing, and translation. Here, we investigated whether paeonol regulates the proliferation and glycolytic reprogramming via ACADM with m6A modification in A549 cells (human non-small cell lung cancer cells). Cell counting kit 8, 5-Bromo-2-deoxyuridine, 5-ethynyl-2'-deoxyuridine (EdU) incorporation, flow cytometry analysis, western blotting and seahorse XFe24 extracellular flux analyzer assays showed that paeonol had a significant inhibitory effect against A549 cell proliferation and glycolysis. Mechanistically, ACADM was a functional target of paeonol. We also showed that the m6A reader YTH domain containing 1 plays an important role in m6A-modified ACADM expression, which is negatively regulated by paeonol, and is involved in A549 cell proliferation and glycolytic reprogramming. These results indicated the central function of paeonol in regulating A549 cell glycolytic reprogramming and proliferation via m6A modification of ACADM.

Given the increasing need of avionics communications and ship electromechanical communications for reliability and real-time transmission, current scheduling schemes waste bandwidth resources. They increase delay because of the low concurrency and the inefficiency of data transmissions in FC-AE-1553 multi-level switching networks. In this study, we first analyze the characteristics of different tasks in the field of avionics communication and establish the FC-AE-1553 network model. We then propose a multi-task hybrid scheduling scheme that includes a static scheduling scheme based on the flow and common divisors of the periods to improve the utilization of bandwidth while ensuring the periodic transmission of deterministic tasks. Further, we exhibit a dynamic bandwidth allocation scheme based on flow and credit ranking to increase throughput and fairness while decreasing the delay of burst tasks. Specifically, to ensure the periodic transmission of deterministic tasks, we divide the transmission time slots according to the common divisor of the period and schedule them in ascending order of period and flow. We update the weights of the credit ranking and flow online, and schedule them in descending order of weight size. The experimental results show that our schemes improve the bandwidth utilization of deterministic tasks by 10% and can balance the throughput and delay of the network. By improving the bandwidth utilization of deterministic tasks, we can provide a better quality of service for burst tasks. When the network can balance its throughput and delay, this shows that the network is efficient and stable.

Objective This research aimed to evaluate the effects of age on growth, tibia development, and intestinal calcium (Ca) and phosphorus (P) transporter gene expressions in broiler chickens. Methods A total of 224 male Arbor Acres broilers were fed with nutrient-adequate diets and reared in eight cages (28 broilers per cage). Eight broilers (one broiler per cage) were selected and killed at 5, 10, 15, 20, 25, 30, 35, and 40 days of age, respectively. Results Body weight continuously increased with age of broiler chickens from 5 to 40 days. The bone weight, ash weight, diameter, and length of the tibia also increased with broiler age. By contrast, the tibia ash, Ca, and P percentages quadratically changed with age (p

Abstract Background Lower back pain and stiffness are the typical symptoms of ankylosing spondylitis (AS). In this study, muscle mass was assessed by muscle density, mechanical elasticity, and area. We investigated the characteristics of lumbar paraspinal-muscle (PSM) mass using muscle ultrasound shear-wave elastography (SWE), as well as the validity of this method for identifying patients with AS. Methods We recruited a representative cohort of 30 AS patients, and 27 healthy volunteers who were age- and sex-matched to the patient study group, investigated the Young’s modulus (YM), cross-sectional area (CSA) and thickness of lumbar multifidus (LM) muscle using SWE. This study did not need to be randomized. Data were collected at the department of ultrasonography of Guangdong Provincial Hospital of Chinese Medicine. We analyzed the data using SPSS version 18.0 (IBM Corp, Armonk, NY, USA). Normal distribution was evaluated by the Shapiro–Wilk test and Q–Q plots. Demographic and baseline data will be analyzed with standard descriptive statistics. Data will be presented as the mean ± standard deviation (SD). Non-normally distributed data are presented as medians with interquartile ranges (IQR). Results Young’s modulus (YM) of SWE in AS patients was significantly higher than that in volunteers. Percentage change in lumbar multifidus (LM) muscle cross-sectional area (CSA) and thickness were significantly lower in AS patients than in healthy volunteers on the left side of the body. Correlation analysis showed a positive correlation between percentage change in CSA and thickness in both volunteers and AS patients. In AS patients, YM was negatively correlated with percentage change of CSA and thickness on the right side, while increased disease duration in AS was associated with increased YM on the left. Conclusion AS patients showed reductions in LM muscle mass and function as the disease progressed, SWE could reflect these changes well. Trial registration. Chinese Clinical Trial Registry, ChiCTR2000031476. Registered 02/04/2020. http://www.chictr.org.cn/index.aspx .

IntroductionFull-thickness skin wound healing remains a serious undertaking for patients. While stem cell-derived exosomes have been proposed as a potential therapeutic approach, the underlying mechanism of action has yet to be fully elucidated. The current study aimed to investigate the impact of exosomes derived from human umbilical cord mesenchymal stem cells (hucMSC-Exosomes) on the single-cell transcriptome of neutrophils and macrophages in the context of wound healing.MethodsUtilizing single-cell RNA sequencing, the transcriptomic diversity of neutrophils and macrophages was analyzed in order to predict the cellular fate of these immune cells under the influence of hucMSC-Exosomes and to identify alterations of ligand-receptor interactions that may influence the wound microenvironment. The validity of the findings obtained from this analysis was subsequently corroborated by immunofluorescence, ELISA, and qRT-PCR. Neutrophil origins were characterized based on RNA velocity profiles.ResultsThe expression of RETNLG and SLC2A3 was associated with migrating neutrophils, while BCL2A1B was linked to proliferating neutrophils. The hucMSC-Exosomes group exhibited significantly higher levels of M1 macrophages (215 vs 76, p < 0.00001), M2 macrophages (1231 vs 670, p < 0.00001), and neutrophils (930 vs 157, p < 0.00001) when compared to control group. Additionally, it was observed that hucMSC-Exosomes elicit alterations in the differentiation trajectories of macrophages towards more anti-inflammatory phenotypes, concomitant with changes in ligand-receptor interactions, thereby facilitating healing.DiscussionThis study has revealed the transcriptomic heterogeneity of neutrophils and macrophages in the context of skin wound repair following hucMSC-Exosomes interventions, providing a deeper understanding of cellular responses to hucMSC-Exosomes, a rising target of wound healing intervention.

1,25-Dihydroxycholecalciferol (1,25-(OH)2-D3) is the final active product of vitamin D. This study aimed to investigate the effects of 1,25-(OH)2-D3 on growth performance, bone development, and calcium (Ca) transporter gene expression levels in the small intestine of broiler chickens. On the day of hatching, 140 female Ross 308 broilers were randomly allotted into two treatments with five replicates (14 birds per replicate). Two levels of 1,25-(OH)2-D3 (0 and 1.25 µg/kg) were added to the basal diet without vitamin D. Results showed that the addition of 1.25 µg/kg 1,25-(OH)2-D3 increased the average daily feed intake and the average daily gain and decreased the feed conversion ratio and mortality in 1- to 19-day-old broiler chickens compared with the basal diet without vitamin D (P0.05). These data indicate that 1,25-(OH)2-D3 upregulated Ca transporter gene transcription and promoted Ca2+ absorption in the small intestine, especially in the proximal intestine (duodenum and jejunum), thereby improving growth performance and bone mineralization in broiler chickens.

Abstract Introduction Poststroke depression (PSD) is the most common mental complication after stroke and has a serious impact on functional outcomes and quality of life. Antidepressants are the first-line treatment for PSD, but many reported side effects remain. Clinical research has shown that acupuncture has a positive effect on PSD. This trial aims to study the efficacy and safety of acupuncture for PSD and to explore its effect on cognitive function. It is hypothesized that acupuncture treatment improves depressive symptoms, cognitive behavior, and negative emotion processing bias in PSD. Methods In this randomized, placebo-controlled, single-blinded trial, fifty-six people with PSD will be randomly allocated into the intervention (n=28) or control (n=28) groups. The intervention group will receive acupuncture treatment, and the control group will receive sham acupuncture treatment, in 20 sessions over 4 weeks. The primary outcome is the change from baseline in the Hamilton Depression Scale-17 (HAMD-17) scores at week 4. Secondary outcomes include the Wisconsin Card Sorting Test (WCST) and latency and amplitude of P1, N170, and P3 of the event-related potentials (ERPs) components to assess the changes in cognitive function and electroencephalography. Outcomes are assessed at baseline and post intervention. Discussion Acupuncture therapy could become an alternative treatment for PSD, and it is expected that this trial will provide reliable clinical evidence for the future use of acupuncture for the treatment of PSD. Trial registration Chinese Clinical Trial Registry ChiCTR1900026948 . Registered on 27 October 2019.

Objective To explore the epidemiological characteristics of patients with lymphoepithelial carcinoma (LEC) of the head and neck and the prognostic factors. Methods We conducted a retrospective cohort study of cases of head and neck LEC retrieved from the Surveillance, Epidemiology and End Results database. Kaplan–Meier survival analysis and the log-rank test were employed to assess overall survival (OS) and cancer-specific survival (CSS). Univariate and multivariate analyses were used to construct Cox regression models. We established nomograms to predict OS and CSS among patients with nasopharyngeal LEC, who were divided into high- and low-risk groups based on the OS nomograms to compare the effects of treatment using the restricted mean survival time (RMST). Results The 5-year OS and CSS rates of the cohort were 70.8% and 74.8%, respectively. Advanced age, unmarried status, black race, distant metastasis, and the absence of surgical treatment were significantly associated with decreased survival rates. RMST did not differ between the combined treatment (radiotherapy and chemotherapy) and radiotherapy monotherapy groups, but chemotherapy alone displayed poor efficacy. Conclusions Head and neck LEC is associated with a favorable prognosis. Radiotherapy plays a significant role in managing patients with nasopharyngeal LEC, which is influenced by multiple prognostic factors.

Photocatalytic conversion of CO2 by using sunlight and TiO2 photocatalysts is a promising approach which produce hydrocarbon fuels to meet the future energy demands with hardly affecting the environment. This systematic review aims to provide rigorous overview of recent progress in TiO2-based CO2 photoreduction to produce hydrocarbon fuels along with future challenges. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method was adopted to perform this systematic review. It uses explicit systematic approaches that are chosen to prevent bias, resulting in accurate data collection which helps to draw reliable conclusions. Peer-reviewed articles published in English language between year 2018–2022 were chosen from two main databases, namely Web of Science and Scopus. Depending on the search criteria 62 articles were selected for reviewing critically. Literature suggests that TiO2-based photocatalysts have been increasingly used for reducing CO2 to hydrocarbon fuels. Morphological alterations and surface modification techniques have been widely utilized to improve the photocatalytic performance and minimize limitations of pure TiO2. Despite extensible efforts in this field, the utilization of hydrocarbon fuels still far away from practical applications. There are some challenges need to be addressed like environment friendly low-cost synthesis and modification method development, maximum visible light utilization, design of photoreactor with suitable product selectivity and kinetic model development for CO2 reduction. This study portrays increased clarity regarding the advances and way forwards of crucial topics TiO2-based CO2 photoreduction. Such systematic review is crucial for researchers and academicians for setting future planning.

Background: To report detailed knowledge about the clinical manifestations, genetic spectrum as well as physical, language, neurodevelopment features and genotype-phenotype correlations of Chinese patients with Mowat-Wilson syndrome (MWS).Methods: We retrospectively collected and analyzed clinical data for twenty-two patients with molecularly confirmed diagnoses. We used Gesell Developmental Schedules (GDS) to assess their neurodevelopment and the Diagnostic Receptive and Expressive Assessment of Mandarin-Infant & Toddler (DREAM-IT) to evaluate their language ability and compared the data with the two types of underlying pathogenic variations.Results: The height and weight of all patients were below the 75th percentile, and microcephaly was observed in 16 of 22 patients (72.7%). Four patients carrying chromosome deletions encompassing the ZEB2 gene were more severely affected. All MWS patients exhibited better performance in cognitive play and social communication than in receptive and expressive language. In the receptive language area, the types of words that children with MWS understood most were nouns, followed by adjectives and verbs.Conclusion: This study delineated the phenotypic spectrum of the largest MWS cohort in China and provided comprehensive profiling of their physical, language, neurodevelopment features and genotype-phenotype correlations.

Introduction: Tislelizumab (anti-programmed cell death protein 1 antibody) showed preliminary antitumor activity and tolerability in patients with advanced solid tumors, including hepatocellular carcinoma (HCC). This study aimed to assess the efficacy and safety of tislelizumab in patients with previously treated advanced HCC. Methods: The multi-regional phase 2 study, RATIONALE-208, examined single-agent tislelizumab (200 mg intravenously every three weeks) in patients with advanced HCC with Child-Pugh A, Barcelona Clinic Liver Cancer stage B or C, and who had received one or more prior lines of systemic therapy. The primary endpoint was objective response rate (ORR), radiologically confirmed per Response Evaluation Criteria in Solid Tumors version 1.1 by Independent Review Committee. Safety was assessed in patients who received ≥1 dose of tislelizumab. Results: Between April 9, 2018 and February 27, 2019, 249 eligible patients were enrolled and treated. After a median study follow-up of 12.7 months, ORR was 13% (n = 32/249; 95% confidence interval [CI], 9–18), including five complete and 27 partial responses. Number of prior lines of therapy did not impact ORR (one prior line, 13% [95% CI, 8–20]; two or more prior lines, 13% [95% CI, 7–20]). Median duration of response was not reached. Disease control rate was 53% and median overall survival was 13.2 months. Of the 249 total patients, grade ≥3 treatment-related adverse events were reported in 38 (15%) patients; the most common was liver transaminase elevations in 10 (4%) patients. Treatment-related adverse events led to treatment discontinuation in 13 (5%) patients or dose delay in 46 (19%) patients. No deaths were attributed to the treatment per investigator assessment. Conclusion: Tislelizumab demonstrated durable objective responses, regardless of the number of prior lines of therapy, and acceptable tolerability in patients with previously treated advanced HCC.

Abstract Background Ankylosing spondylitis (AS) is a high-incidence disease in young men that interferes with patients’ physical and mental wellbeing and overall quality of life (QoL). It is often accompanied by arthralgia, stiffness, and limited lumbar flexibility. Acupuncture is safe and effective for reducing the symptoms of AS, but the underlying mechanisms by which it does so are not fully understood. Therefore, to objectively assess acupuncture efficacy, which is critical for patients making informed decisions about appropriate treatments, we will use shear-wave elastography (SWE) and superb microvascular imaging (SMI) ultrasound techniques to evaluate elasticity of lumbar paraspinal muscles and blood flow to the sacroiliac joint (SIJ) in AS. Methods We will recruit a total of 60 participants diagnosed with AS and 30 healthy subjects. Participants will be randomly allocated 1:1 to either an acupuncture group or a sham control acupuncture group. Primary-outcome measures will be musculoskeletal ultrasound, Ankylosing Spondylitis Quality of Life Scale (ASQoL), Bath Ankylosing Spondylitis Metrology Index (BASMI), and the Visual Analogue Scale (VAS) for pain. Secondary outcome measures will be the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Function Index (BASFI), and Fatigue Scale-14 (FS-14). We will monitor the effect of acupuncture or sham acupuncture on blood flow and SIJ inflammation using SMI, lumbar-muscle stiffness using SWE and the lumbar paraspinal-muscle cross-sectional area (CSA) using a two-dimensional (2D) grayscale imaging. QoL, physical function, and fatigue will be assessed using an evaluation scale or questionnaire developed for this study, with outcomes measured by the ASQoL, BASMI, BASDAI, BASFI, and FS-14. Healthy subjects will not receive acupuncture but undergo only musculoskeletal ultrasound at baseline. Acupuncture and sham control acupuncture interventions will be conducted for 30 min, 2–3 times/week for 12 weeks. Musculoskeletal ultrasound will be conducted at baseline and post-intervention, while other outcomes will be measured at baseline, 6 weeks, and post-intervention. The statistician, outcome assessor, and participants will be blinded to treatment allocation. Discussion The results of this single-blinded, randomized trial with sham controls could help demonstrate the efficacy of acupuncture and clarify whether musculoskeletal ultrasound could be used to evaluate AS. Trial registration ClinicalTrials.gov ChiCTR2000031476 . Registered 3 April 2020.

This study collected summer meltwater runoff samples from several glacier watersheds of the northeast Tibetan Plateau during June-July 2017, and measured the concentrations of 17 trace elements (Li, Be, Sc, V, Cr, Co, Ni, Cu, Zn, Ga, Rb, Mo, Cd, In, Sb, Cs, Ba) in meltwater suspended particulate matter (SPM), in order to reveal the elemental concentration, spatial distribution, and water quality in remote glacier watershed under regional anthropogenic activities. Results showed that, the concentration of heavy metal elements was relatively high in Yuzhufeng Glacier basin, ranging from 0.57 μg/L (In) to 1,551.6 μg/L (Ba), whereas in Qiyi Glacier basin it was the lowest, ranging from 0.02 to 85.05 μg/L; and relatively medium in other glacier watersheds, with total elemental concentration varying from 1,503.9 to 1726.2 μg/L. Moreover, enrichment factors (EFs) of SPM heavy metals showed significantly higher value in the downstream than that of upper glacier region of the watershed. Most heavy metals with low EFs mainly originated from crust dust, while others with higher EFs (e.g., Cd, Sb) probably originated from anthropogenic sources. Spatially, the EFs of heavy metals were higher in Yuzhufeng and Laohugou Glacier basins; while in other regions the EFs were relatively low, which may be caused by regional land-surface and atmospheric environmental differences surrounding the various glacier watersheds. Compared with other remote locations in global range, heavy metals level (e.g., Cu, Ni, and Zn) in this region is relatively higher. Meanwhile, we find that, though the water quality of the glacier basin in northeast Tibetan Plateau was relatively clean and pollution-free, it is still obviously affected by regional anthropogenic activities. Mining activities, transportation and natural weathering and erosion processes in the study areas have important effects on the content of heavy metal pollutants of river-water SPM in the glacier watershed. Moreover, backward air-mass trajectories demonstrated the potential atmospheric pollutants transport from the surrounding cities and suburbs, to deposit in the snowpack and glaciers, and then melted out and released into meltwater runoff. This study provides a new perspective on more complete view of heavy metals distribution in glacier watershed, and new understanding for the cryosphere water environment evaluation in the Tibetan Plateau region.

Abstract Wnt signaling plays a major role in early neural development. An aberrant activation in Wnt/β-catenin pathway causes defective anteroposterior patterning, which results in neural tube closure defects (NTDs). Changes in folate metabolism may participate in early embryo fate determination. We have identified that folate deficiency activated Wnt/β-catenin pathway by upregulating a chorion-specific transcription factor Gcm1. Specifically, folate deficiency promoted formation of the Gcm1/β-catenin/T-cell factor (TCF4) complex formation to regulate the Wnt targeted gene transactivation through Wnt-responsive elements. Moreover, the transcription factor Nanog upregulated Gcm1 transcription in mESCs under folate deficiency. Lastly, in NTDs mouse models and low-folate NTDs human brain samples, Gcm1 and Wnt/β-catenin targeted genes related to neural tube closure are specifically overexpressed. These results indicated that low-folate level promoted Wnt/β-catenin signaling via activating Gcm1, and thus leaded into aberrant vertebrate neural development.

The trends exhibited by the parameters that describe the mechanical behaviour of major ampullate gland silk fibers spun by Argiope bruennichi spiders is explored by performing a series of loading-unloading tests at increasing values of strain, and by the subsequent analysis of the true stress-true strain curves obtained from these cycles. The elastic modulus, yields stress, energy absorbed, and energy dissipated in each cycle are computed in order to evaluate the evolution of these mechanical parameters with this cyclic straining. The elastic modulus is observed to increase steadily under these loading conditions, while only a moderate variation is found in the yield stress. It is also observed that a significant proportion of the energy initially absorbed in each cycle is not only dissipated, but that the material may recover partially from the associated irreversible deformation. This variation in the mechanical performance of spider silk is accounted for through a combination of irreversible and reversible deformation micromechanisms in which the viscoelasticity of the material plays a leading role.

Abstract Acute leukemias of ambiguous lineage, not otherwise specified (ALAL-NOS) is a rare type of acute leukemia. Management of relapse/refractory (R/R) patients is still challenging.traditional chemotherapy treatment is not effective. In this paper, we reported 6 R/R patients diagnosed as ALAL-NOS in our hospital, who were treated with venetoclax based treatment (venetoclax combining with azacitidine or chemotherapy). All 6 patients achieved CR. Five of the six patients received allo-HSCT, four patients were still alive in CR until the follow-up day. Our data provide preliminary evidence and show that venetoclax based regimens are effective and safety in patients with R/R ALAL-NOS.

Background: Recent studies highlight the carcinogenesis role of SHC-adaptor protein 1 (SHC1) in cancer initiation, development, and progression. However, its aberrant expression, diagnostic and prognostic value remain unknown in a variety of tumors.Methods: The SHC1 expression profiles were analyzed using GTEx database, TCGA database, Oncomine and CPTAC database. The survival analysis was conducted using GEPIA2, Kaplan-Meier Plotter, UALCAN, and PrognoScan. The diagnostic values of SHC1 were calculated with the “pROC” package in R software. The genetic alteration of SHC1 and mutations were analyzed using cBioPortal. TIMER2 was employed to estimate the correlations between SHC1 expression and tumor-infiltrating immune cells in the TCGA cohort. Enrichment analysis of SHC1 was conducted using the R package “clusterProfiler.”Results: SHC1 was ubiquitously highly expressed and closely associated with worse prognosis of multiple major cancer types (all p < 0.05). Further, SHC1 gene mutations were strongly linked to poor OS and DFS in SKCM (all p < 0.05). An enhanced phosphorylation level of SHC1 at the S139 site was observed in clear cell RCC. Additionally, the results revealed SHC1 expression was strongly linked to TMB, MMRs, MSI, TAMs, DNA methylation, m6A RNA methylation, tumor-associated immune infiltration, and immune checkpoints in multiple cancers (all p < 0.05). In addition, the results of the ROC analysis indicated the SHC1 exhibited strong diagnostic capability for KICH (AUC = 0.92), LIHC (AUC = 0.95), and PAAD (AUC = 0.95). Finally, enrichment analysis indicated that SHC1 may potentially involve in the regulation of numerous signaling pathways in cancer metabolism and protein phosphorylation-related functions.Conclusions: These findings highlight that SHC1 plays an important role in the tumor immune microenvironment, and SHC1 has been identified to have prognostic and diagnostic value in multiple cancers. Thus, SHC1 is a potential target for cancer immunotherapy and effective prognostic and diagnostic biomarker.

IntroductionAntidepressants are the front-line treatments for major depressive disorder (MDD), but remain unsatisfactory in outcome. An increasing number of patients are interested in acupuncture and moxibustion treatment as complementary therapies. This study aims to evaluate the efficacy and safety of integrative acupuncture and moxibustion (iAM) treatment in patients with MDD.Methods and AnalysisThis multicenter, single-blind, 2 × 2 factorial randomized trial will enroll 592 patients with MDD of moderate severity from nine hospitals. All patients will be randomized, in a ratio of 2:2:2:1, through a computerized central randomization system, into four groups (the combined, iAM-only, sertraline-only, and placebo groups). Participants will undergo a 12-week intervention with either 50 mg of sertraline or a placebo once a day and active/sham iAM treatment three times per week. The primary outcome is depression severity, assessed using the Hamilton Depression Scale-17. The secondary outcomes include self-rated depression severity, anxiety, and sleep quality. The primary and secondary outcomes will be measured at weeks 0, 4, 8, 12, and the 8th week posttreatment. Safety will be evaluated through liver and kidney function tests conducted before and after treatment and through monitoring of daily adverse events. An intent-to-treat principle will be followed for the outcome analyses.ConclusionThis trial will provide sufficient evidence to ascertain whether iAM is effective and safe for treating MDD and provides a suitable combination strategy for treating MDD.Clinical Trial Registration[www.chictr.org.cn], identifier [ChiCTR2100042841].

Chinese fir (Cunninghamia lanceolata), which is an important coniferous tree species in China, is mainly planted in acidic soils with toxic aluminum (Al) levels. However, the consequences of Al toxicity and its resistance mechanism in Chinese fir remain largely uncharacterized. In this study, the Al-induced modification and possible role of cell wall in regulating Al tolerance in Chinese fir were investigated by using seedlings with contrasting Al tolerance, namely, Al-sensitive (YX02) and Al-resistant (YX01) genotypes. The results in present work showed that Al treatment resulted in a dose- and time-dependent inhibition of root growth and oxidative damage in both genotypes, but more in YX02 than in YX01. The severe oxidative damage observed in YX02 under Al stress was found to correlate with lower antioxidant enzyme activities as compared with YX01. The greater root growth inhibition observed in YX02 compared with YX01 was associated with a higher accumulation of Al in pectin and hemicllulose 1 (HC1) fraction because of the higher pectin and HC1 contents and the lower degree of pectin demethylation due to enhanced pectin methylesterase activity in YX02, which ultimately enhanced cell wall binding capacity for Al in YX02. Taken together, our results suggested that enhancement of antioxidant enzyme activities and cell wall modification-induced Al exclusion are the two mechanisms responsible for the Al tolerance of Chinese fir.

Abstract Optimizing the induction therapy of acute myeloid leukemia (AML) may improve the remission rate and reduce the risk of relapse, thereby extend survival. Cyclophosphamide (CTX) shows benefit in treating relapsed and refractory AML patients, but it has not been reported in first‐line induction regimens. To assess the efficacy and safety of CTX and moderate‐dosage cytarabine (Ara‐C) as induction chemotherapy in newly diagnosed adult AML, 40 patients were enrolled to receive CTX (20 mg/kg/d) for 4 consecutive days and Ara‐C for 3 (1 g/m2 q12h, CA4+3) or 5 (1 g/m2 qd, CA4+5) days. With one course of induction chemotherapy, the overall response rate and the complete remission rate (CR) was 82.5% (33/40) and 77.5% (31/40), respectively. The expected 5 years overall survival and relapse‐free survival was 64% in patients experienced CR and fulfilled consolidation therapy. The neutrophil and platelet recovery time were 17 (range, 10–20) days and 16.5 (range, 12–30) days in the CA4+3 group, faster than that of 20 (16‐36) days and 20 (14‐36) days in the CA4+5 group (P = .006 and P = .006). The cyclophosphamide and cytarabine (CA) regimen was generally safe and had reversible adverse effects. The patients who failed to respond to the CA regimen did not benefit from a second course of other traditional induction chemotherapy either. In conclusion, the combined regimen of CTX and Ara‐C represents a promising therapeutic approach to induce the first CR of newly diagnosed adult AML.

Background: At present, there are a variety of treatment strategies for percutaneous coronary intervention. The role of drug-coated balloon (DCB) in the treatment of side branch for de novo coronary bifurcated lesions (CBL) is unclear.Objective: To examine the effect of DCB in side branch protection for de novo CBL.Methods: Electronic databases, including Pubmed, Embase, the Web of science, Cochrance library, CNKI, CBM, WanFang Data and VIP were searched for studies that compared DCB with non-drug-coated balloon (NDCB) in side branch protection for de novo CBL from inception through July 7th, 2021. The primary outcome was target lesion revascularization (TLR). Secondary clinical outcomes included myocardial infarction (MI), cardiac death (CD). The angiographic outcomes included side branch late lumen loss (LLL), minimum lumen diameter (MLD), diameter stenosis (DS) and binary restenosis (BR). The target lesion failure (TLF) was also analyzed.Results: A total of 10 studies, including 5 randomized controlled trials and 5 non-randomized observational studies, with 934 patients were included. Meta-analysis results of angiographic outcomes suggested that DCB group had the less LLL, DS and BR and the higher MLD compared with NDCB group at follow-up (P < 0.05). Meta-analysis results of clinical outcomes suggested that the significant difference in the TLR, MI and CD between DCB group and NDCB group has not been found yet (P > 0.05). However, the MACE of DCB group was significantly less than that of NDCB group at 9-month follow-up [OR = 0.21, 95%CI (0.05, 0.84), P = 0.03] and 12-month follow-up [OR = 0.45, 95%CI (0.22, 0.90), P = 0.02]. In addition, there was no significant difference in TLF between DCB group and NDCB group (P > 0.05).Conclusions: DCB had great effect in side branch protection for de novo CBL at short and medium-term follow-up with no reduction in the procedural success rate.Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=267426, PROSPERO [Identifier: CRD42021267426].

Hearing loss (HL) is one of the most common disabilities in the world. In industrialized countries, HL occurs in 1–2/1,000 newborns, and approximately 60% of HL is caused by genetic factors. Next generation sequencing (NGS) has been widely used to identify many candidate genes and variants in patients with HL, but the data are scattered in multitudinous studies. It is a challenge for scientists, clinicians, and biologists to easily obtain and analyze HL genes and variant data from these studies. Thus, we developed a one-stop database of HL-related genes and variants, Gene4HL (http://www.genemed.tech/gene4hl/), making it easy to catalog, search, browse and analyze the genetic data. Gene4HL integrates the detailed genetic and clinical data of 326 HL-related genes from 1,608 published studies, along with 62 popular genetic data sources to provide comprehensive knowledge of candidate genes and variants associated with HL. Additionally, Gene4HL supports the users to analyze their own genetic engineering network data, performs comprehensive annotation, and prioritizes candidate genes and variations using custom parameters. Thus, Gene4HL can help users explain the function of HL genes and the clinical significance of variants by correlating the genotypes and phenotypes in humans.

ObjectivesThis study aimed to determine the prevalence and localization of complement factor C4d in renal biopsies from patients with lupus nephritis (LN), as well as its associations with the disease’s clinico-pathological features. The correlation between arteriolar C4d deposition and renal microvascular lesions (RVLs) was further analyzed.MethodsA total of 325 biopsy-proven LN patients were enrolled, and their clinico-pathological data were collected. C4d staining of renal biopsies was performed by immunohistochemistry. The associations between C4d deposition and the clinico-pathological features were further analyzed.ResultsC4d deposition was present in most (98.8%) renal specimens in our cohort. These deposits were localized in the glomeruli (98.2%), tubular basement membrane (TBM) (43.7%), arterioles (31.4%), and peritubular capillary (33.8%). Patients with TBM C4d staining had higher disease activity (measured with the Systemic Lupus Erythematous Disease Activity Index) and higher National Institutes of Health pathological activity and chronicity indices (all P < 0.01). Patients with arteriolar C4d deposition were more likely to develop RVLs (91.2%) compared to those with no arteriolar C4d deposition (78.0%; P = 0.004), especially with two or more types of RVLs (P < 0.001). During the mean follow-up of 55.8 months, arteriolar C4d was related to worse renal outcomes [hazard ration (HR): 2.074, 95% confidence interval (CI) 1.056–4.075, P = 0.034]. Multivariate Cox hazard analysis showed that co-deposition of arteriolar C4d and C3c was an independent risk factor (HR: 3.681, 95% CI 1.519–8.921, P = 0.004) for predicting renal outcomes.ConclusionsC4d deposition was common in renal tissues from LN patients. TBM C4d deposition was related to the disease activity, and arteriolar C4d deposition was associated with RVLs and worse renal outcomes.

Protection against hypoxia injury is an important therapeutic strategy for treating hypertensive nephropathy. In this study, the effects of Qian Yang Yu Yin granule (QYYY) on spontaneously hypertensive rats fed with high salt diet and HEK293T cells exposed to hypoxia were investigated. After eight weeks’ treatment of QYYY, blood pressure, serum creatinine, serum cystatin C, blood urea nitrogen, urinary β2-microglobulin, urinary N-acetyl-β-glucosaminidase, and urinary microalbumin were assessed. The changes of hypoxia-inducible factor-1α (HIF-1α), pyruvate kinase M2 (PKM2), glucose transport 1 (GLUT1), lactate dehydrogenase A (LDH-A), connective tissue growth factor (CTGF), transforming growth factor-β1 (TGF-β1), ATP, lactate, pyruvate, and pathology were also assessed in vivo. HEK293T cells pre-treated with QYYY and/or HIF-1α over expressing cells were cultured in a three gas hypoxic incubator chamber (5% CO2, 1% O2, 94% N2) for 12 h and then the expressions of HIF-1α, PKM2, GLUT1, LDH-A, CTGF, TGF-β1, ATP, lactate, and pyruvate were detected. Our results showed that QYYY promoted the indicators of renal inflammation and fibrosis mediated by HIF-1α/PKM2 positive feedback loop in vivo and vitro. Our findings indicated that QYYY treated hypertensive nephropathy by regulating metabolic reprogramming mediated by HIF-1α/PKM2 positive feedback loop.

The projected increase in temperature and water scarcity represents a challenge for winegrowers due to changing climatic conditions. Although heat and drought often occur concurrently in nature, there is still little known about the effects of water stress (WS) on grapevines in hot environments. This study aimed to assess whether the grapevine’s physiological and spectral responses to WS in hot environments differ from those expected under lower temperatures. Therefore, we propose an integrated approach to assess the physiological, thermal, and spectral response of two grapevine varieties (Vitis vinifera L.), Grenache and Shiraz, to WS in a hot environment. In a controlled environment room (CER), we imposed high-temperature conditions (TMIN 30 °C–TMAX 40 °C) and compared the performance of well-watered (WW) and WS-ed potted own-rooted Shiraz and Grenache grapevines (SH_WW, SH_WS, GR_WW, and GR_WS, respectively). We monitored the vines’ physiological, spectral, and thermal trends from the stress imposition to the recovery after re-watering. Then, we performed a correlation analysis between the physiological parameters and the spectral and thermal vegetation indices (VIs). Finally, we looked for the best-fitting models to predict the physiological parameters based on the spectral VIs. The results showed that GR_WS was more negatively impacted than SH_WS in terms of net photosynthesis (Pn, GR-WS = 1.14 μmol·CO2 m−2·s−1; SH-WS = 3.64 μmol·CO2 m−2·s−1), leaf transpiration rate (E, GR-WS = 1.02 mmol·H2O m−2·s−1; SH-WS = 1.75 mmol·H2O m−2·s−1), and stomatal conductance (gs, GR-WS = 0.04 mol·H2O m−2·s−1; SH-WS = 0.11 mol·H2O m−2·s−1). The intrinsic water-use efficiency (WUEi = Pn/gs) of GR_WS (26.04 μmol·CO2 mol−1 H2O) was lower than SH_WS (34.23 μmol·CO2 mol−1 H2O) and comparable to that of SH_WW (26.31 μmol·CO2 mol−1 H2O). SH_WS was not unaffected by water stress except for E. After stress, Pn, gs, and E of GR_WS did not recover, as they were significantly lower than the other treatments. The correlation analysis showed that the anthocyanin Gitelson (AntGitelson) and the green normalised difference vegetation index (GNDVI) had significant negative correlations with stem water potential (Ψstem), Pn, gs, and E and positive correlation with WUEi. In contrast, the photochemical reflectance index (PRI), the water index (WI), and the normalised difference infrared index (NDII) showed an opposite trend. Finally, the crop water stress (CWSI) had significant negative correlations with the Ψstem in both varieties. Our findings help unravel the behaviour of vines under WS in hot environments and suggest instrumental approaches to help the winegrowers managing abiotic stress.

Aspirin is one of the most commonly prescribed medications. Evidence shows that it can even treat and prevent intestinal tumors. However, it has also caused a great deal of controversy due to its intestinal side effects. We therefore explored whether aspirin was beneficial or harmful to the intestines. We used aspirin continuously interfered with C57BL/6 J mice for 48 weeks, examining their intestinal tissues at 13, 26 and 48 weeks to determine the drug’s effect on the intestines. In addition, we used flow cytometry (FCM) used to detect T cells and expression of T-cell immunoreceptor with immunoglobulin (Ig)– and tyrosine-based inhibitory motif (ITIM) domain (TIGIT) on their surfaces to determine aspirin’s immunomodulatory effects. The results showed that long-term aspirin intervention could reverse damage to the intestines, an effect related to the drug’s significant inhibitory effect on TIGIT. The change in TIGIT level could regulate T-cell subsets, so that counts of Cluster of Differentiation 4 (CD4)+/chemokine (C-X3-C motif) receptor 3 (CXCR3)+ T-helper 1 (Th1) cells and CD4+/interleukin-4 (IL-4)+ Th2 cells increased, while those of CD4+/C-C chemokine receptor type 6 (CCR6)+ Th17 cells and CD4+/CD25+ regulatory T cells (Tregs) decreased. In summary, we demonstrated that long-term aspirin intervention could inhibit TIGIT, regulating T cells to reverse damage to the intestines. Furthermore, aspirin is a potential therapy for diseases related to an increase in TIGIT.

Meckel’s diverticulum (MD) is a relatively common true congenital diverticulum on the ileum. Bleeding caused by polypoid hyperplasia of ectopic gastric mucosa in MD is rare. A 14-year-old Chinese boy presented with intermittent melena and haematochezia for 1 month. Laboratory data showed normocytic anaemia. Gastroscopic findings were normal. The patient underwent exploratory laparotomy without bowel preparation on day 2 because of sudden haematochezia and decreased haemoglobin. Intraoperative colonoscopy revealed inflammatory changes in the terminal ileal mucosa with diffuse haemorrhage. Melena with decreased haemoglobin recurred 20 days after the first operation. Computed tomography (CT) and angiography revealed a tubular lesion that was localised in the right lower abdominal quadrant. Single-photon emission computed tomography/computed tomography (SPECT/CT) fusion imaging with 99m-technetium pertechnetate confirmed moderately increased uptake in the distal ileum. Retrograde double-balloon enteroscopy (DBE) showed a diverticulum with prominent mucosal polypoid hyperplasia at an insertion depth of 100 cm from the anastomotic stoma. Diverticulectomy and end-to-end anastomosis were performed, and MD was confirmed by a histopathological examination. The patient’s postoperative recovery was uneventful during the 2-month follow-up. MD with polypoid hyperplasia of ectopic gastric mucosa is rare. Complementary use of DBE and SPECT/CT can accurately diagnose MD by providing anatomical and functional information.

Zoigê Plateau, China’s largest plateau marsh wetland, has experienced large-scale degradation of the marsh wetland and evolution of the wetland landscape pattern over the past 40 years due to climate warming and human activities. How exactly do the wetland landscape pattern characteristics change? How do climatic change and human activities affect the wetland evolution? These questions are yet to be systematically investigated. In order to investigate changes to the marsh wetland on the Zoigê Plateau, field investigations, spatial and statistical analysis were undertaken. Findings from our study indicate that from 1977–2016, the area of marsh wetland on the Plateau reduced by 56.54%, approximately 66,700 hm2 of marsh wetland has been lost. The centroids of both marsh and marshy meadow migrated and the landscape centroid migration behaviors were also correlated with the distribution and variation of the marsh wetland on different slopes. In addition, the number of marsh landscape patches initially increased before decreasing; the number of marshy meadow landscape patches also recorded an initial increase, followed by a decline before a final increase. As the effects of human activities weakened, the aggregation degrees of both marsh and marshy meadow increased. Overall, the fragmentation degree, diversity and fractal dimension of the marsh wetland all declined. An investigation into the driving factors affecting the Plateau area shows that the increase of annual average temperature was the natural factor while trenching and overgrazing were the main human factors resulting in wetland degradation. Results from this study provide basic data and theoretical foundation for the protection and restoration of marsh wetland in alpine regions.

ObjectiveDanhong Injection (DHI) has been widely used to treat various diseases in China for many years. The objective of this systematic review was to evaluate the efficacy of DHI combined with antihypertensive drugs for treatment of hypertensive nephropathy.MethodsSeven databases were searched from inception to September 21st, 2019. Randomized controlled trials comparing DHI combined with antihypertensive drugs versus antihypertensive drugs alone were extracted. The primary outcome was microalbuminuria (mALB). Secondary outcomes included systolic blood pressure (SBP), diastolic blood pressure (DBP), and serum creatinine (SCr).ResultsFifteen studies were included in the meta-analysis, which indicated that DHI combined with antihypertensive drugs has advantages compared with antihypertensive drugs alone for reducing mALB [weighted mean difference (WMD) = −12.86, 95% confidence interval (CI) (−14.72, −11.0), P < 0.01], lowering SBP [WMD = −2.84, 95% CI (−4.56, −1.12), P = 0.001] and DBP [WMD = −2.38, 95% CI (−4.34, −0.43), P = 0.017], and decreasing SCr [WMD = −40.45, 95% CI (−55.69, −25.21), P < 0.01].ConclusionThe combination of DHI with antihypertensive drugs appears to be more effective than antihypertensive drugs alone for treatment of hypertensive nephropathy. A moderate duration (≤4 weeks) of DHI administration is reasonable, and longer treatment with DHI should be avoided, according to the results of subgroup analysis.

The objective of this paper is to study the variation in the physical and mechanical properties of expanded perlite mortar with environmental factors and analyze its deterioration mechanism. In this paper, the influence of the heat-rain cyclic and natural aging on the physical and mechanical properties of expanded perlite mortar has been studied. The expanded perlite mortar specimens were subjected to 80 heat-rain cycles (the maximum temperature rises to 70 °C, and the spray volume reaches 1 l/(m ^2 min)) and 60-day natural aging tests (the daily average temperature is 23 °C, with the maximum temperature reaching 36 °C). The corresponding mass loss rate, water absorption, and compressive strength of the specimens at every 10 heat-rain cycles and 10 days were determined. The results show that the mass loss rate gradually increases with the increase in heat-rain cycles and the natural aging days. The variation range was found as about 0.2%∼0.7% and −0.4%∼0.2%, respectively. The water absorption rate gradually decreases with the number of heat-rain cycles and natural aging days; however, the decay rate of the water absorption rate differs by orders of magnitude in the two weathering conditions. The compressive strength does not have an obvious change with the number of heat rain cycles, but it first increases and then decreases with the number of natural aging days. Under artificial and natural aging, the deterioration mechanism and aging speed of expanded perlite mortar are much different. The comparative analysis of the physical and mechanical properties of expanded perlite mortar under artificially accelerated and natural aging conditions can further reveal its evolution model and the corresponding relationships under the two conditions and provide a theoretical basis for establishing a more scientific and reasonable aging system.