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Abstract Objectives This study aims to investigate the links between the clinical, demographic, and psychosocial factors and cancer-related worry in patients with early-stage lung cancer after surgery. Methods The study utilized a descriptive cross-sectional design. Questionnaires, including assessments of cancer-related worry, symptom burden, illness perception, psychological resilience, coping modes, social support and participant characteristics, were distributed to 302 individuals in early-stage lung cancer patients after surgery. The data collection period spanned from January and October 2023. Analytical procedures encompassed descriptive statistics, independent Wilcoxon Rank Sum test, Kruskal-Wallis- H- test, Spearman correlation analysis, and hierarchical multiple regression. Results After surgery, 89.07% had cancer-related worries, with a median (interquartile range, IQR) CRW score of 380.00 (130.00, 720.00). The most frequently cited concern was the cancer itself (80.46%), while sexual issues were the least worrisome (44.37%). Regression analyses controlling for demographic variables showed that higher levels of cancer-related worry (CRW) were associated with increased symptom burden, illness perceptions, and acceptance-rejection coping modes, whereas they had lower levels of psychological resilience, social support and confrontation coping modes, and were more willing to obtain information about the disease from the Internet or applications. Among these factors, the greatest explanatory power in the regression was observed for symptom burden, illness perceptions, social support, and sources of illness information (from the Internet or applications), which collectively explained 52.00% of the variance. Conclusions Healthcare providers should be aware that worry is a common issue for early stage lung cancer survivors with a favorable prognosis. During post-operative recovery, physicians should identify patient concerns and address unmet needs to improve patients’ emotional state and quality of life through psychological support and disease education.

Abstract Autism Spectrum Disorder (ASD) is a neurodevelopmental condition that affects an individual's behavior, speech, and social interaction. Early and accurate diagnosis of ASD is pivotal for successful intervention. The limited availability of large datasets for neuroimaging investigations, however, poses a significant challenge to the timely and precise identification of ASD. To address this problem, we propose a breakthrough approach, GARL, for ASD diagnosis using neuroimaging data. GARL innovatively integrates the power of GANs and Deep Q-Learning to augment limited datasets and enhance diagnostic precision. We utilized the Autistic Brain Imaging Data Exchange (ABIDE) I and II datasets and employed a GAN to expand these datasets, creating a more robust and diversified dataset for analysis. This approach not only captures the underlying sample distribution within ABIDE I and II but also employs deep reinforcement learning for continuous self-improvement, significantly enhancing the capability of the model to generalize and adapt. Our experimental results confirmed that GAN-based data augmentation effectively improved the performance of all prediction models on both datasets, with the combination of InfoGAN and DQN's GARL yielding the most notable improvement.

Burkholderia semiarida was previously identified solely as a plant pathogen within the Burkholderia cepacia complex. We present a case in China involving recurrent pneumonia attributed to B. semiarida infection. Of note, the infection manifested in an immunocompetent patient with no associated primary diseases and endured for >3 years.

Abstract Background It remains unknown how the patterns of change of social isolation and loneliness are associated with the onset of cardiovascular disease (CVD) and mortality. We aimed to investigate the longitudinal association of changes in social isolation and loneliness with incident CVD, all-cause mortality, CVD mortality and subsequent cardiac function. Methods This prospective cohort study included 18,258 participants aged 38–73 years who participated in visit 0 (2006–2010) and visit 1 (2012–2013) using UK Biobank (mean age 57.1, standard deviation [SD] 7.4; 48.7% males). Social isolation or loneliness was categorized into four patterns: never, transient, incident, and persistent. Incident CVD, all-cause and CVD mortality were ascertained through linkage data. Cardiac function was assessed by cardiovascular magnetic resonance imaging in a subsample (N = 5188; visit 2, since 2014). Results Over a median follow-up of 8.3 (interquartile range [IQR] 8.1–8.6) years, compared with never social isolation, persistent social isolation was associated with the higher risk of incident CVD (hazard ratio [HR] 1.17, 95% confidence interval [CI] 1.03–1.33), all-cause (1.42, 1.12–1.81) and CVD (1.53, 1.05–2.23) mortality. Likewise, persistent loneliness was strongly associated with the greater risk of incident CVD (1.13, 1.00–1.27), all-cause (1.28, 1.02–1.61) and CVD mortality (1.52, 1.06–2.18). Conclusions Persistent social isolation and loneliness posed a substantially higher risk for incident CVD, all-cause and CVD mortality, and cardiac dysfunction than other patterns. Persistent social isolation and loneliness, along with an increasing cumulative score, are associated with lower cardiac function. Graphical Abstract

Extensive research has been conducted to investigate the impact of capsaicin (CAP) on lipid metabolism, focusing specifically on its interaction with the vanilloid subtype 1 (TRPV1) ion channel. Additionally, studies have illuminated the role of Akkermansia muciniphila (A. muciniphila), a specific strain of intestinal microbiota, in lipid metabolism. In this study, a model utilizing resiniferatoxin (RTX) was employed to deactivate TRPV1 ion channels in germ-free mice, followed by the administration of A. muciniphila via gavage. Following the collection of intestinal tissues for a comprehensive analysis, employing histopathology, qPCR, and ELISA techniques, our findings revealed a significant upregulation of MUC2 and MUC3 expression induced by CAP. This upregulation resulted in the thickening of the colonic mucus layers. Notably, this effect was absent when TRPV1 was selectively inhibited. Moreover, there was no discernible impact on goblet cells. The findings strongly indicate that CAP influences the system by activating the TRPV1 ion channel, thereby enhancing the expression of mucin MUC2 and promoting an augmentation in the thickness of the mucous layer. This activation, in turn, supplies A. muciniphila with an ample source of carbon and nitrogen. This insight potentially clarify the underlying mechanism through which CAP facilitates the increase in A. muciniphila abundance.

Abstract Schizophrenia is a mental health disorder characterized by functional dysconnectivity. Eigenvector centrality mapping (ECM) has been employed to investigate alterations in functional connectivity in schizophrenia, yet the results lack consistency, and the genetic mechanisms underlying these changes remain unclear. In this study, whole-brain voxel-wise ECM analyses were conducted on resting-state functional magnetic resonance imaging data. A cohort of 91 patients with schizophrenia and 91 matched healthy controls were included during the discovery stage. Additionally, in the replication stage, 153 individuals with schizophrenia and 182 healthy individuals participated. Subsequently, a comprehensive analysis was performed using an independent transcriptional database derived from six postmortem healthy adult brains to explore potential genetic factors influencing the observed functional dysconnectivity, and to investigate the roles of identified genes in neural processes and pathways. The results revealed significant and reliable alterations in the ECM across multiple brain regions in schizophrenia. Specifically, there was a significant decrease in ECM in the bilateral superior and middle temporal gyrus, and an increase in the bilateral thalamus in both the discovery and replication stages. Furthermore, transcriptional analysis revealed 420 genes whose expression patterns were related to changes in ECM, and these genes were enriched mainly in biological processes associated with synaptic signaling and transmission. Together, this study enhances our knowledge of the neural processes and pathways involved in schizophrenia, shedding light on the genetic factors that may be linked to functional dysconnectivity in this disorder.

Background: Emerging evidence has linked childhood maltreatment with cardiovascular disease risk; however, the association between childhood maltreatment and cardiac arrhythmias remains unclear. Moreover, any genetic predispositions to atrial fibrillation (AF), a common cardiac arrhythmia associated with an elevated risk of stroke, heart failure, and mortality, that modify such associations have been undocumented.Purpose: To examine the associations between childhood maltreatment and incident arrhythmias, and whether a genetic predisposition to arrhythmias modifies these associations.Methods: This prospective analysis included 151,741 participants from the UK Biobank (mean age 55.8 years, 43.4% male). Childhood maltreatment, including five types, was measured using the Childhood Trauma Screener (CTS). Incident arrhythmias (AF, ventricular arrhythmias [VA], and bradyarrhythmia [BA]) were documented through linked hospital admission and death registry. Weighted AF genetic risk score was calculated. Cox proportional hazard models were conducted to test for associations between childhood maltreatment and incident arrhythmias.Results: During a median follow-up of 12.21 years (interquartile range, 11.49–12.90 years), 6,588 AF, 2,093 BA, and 742 VA events occurred. Compared with the absence of childhood maltreatment, having 3–5 types of childhood maltreatment was associated with an increased risk of incident AF (HR, 1.23; 95%CI 1.09–1.37), VA (HR, 1.39; 95%CI 1.03–1.89), and BA (HR, 1.32; 95%CI 1.09–1.61) after adjusting demographic, socioeconomic and lifestyle factors. The associations between cumulative type of childhood maltreatment and the risk of AF (Poverall

Abstract Background Gastric cancer (GC) is a common malignancy and a leading cause of cancer-related death with high morbidity and mortality. Methyl-CpG binding domain protein 3 (MBD3), a key epigenetic regulator, is abnormally expressed in several cancers, participating in progression and metastasis. However, the role of MBD3 in GC remains unknown. Methods MBD3 expression was assessed via public databases and validated by western blotting and quantitative real-time polymerase chain reaction (qRT-PCR). The prognosis of MBD3 was analysed via bioinformatics based on the TCGA dataset. The migration, invasion and proliferation of GC cells were examined by transwell, wound healing, cell counting kit (CCK)-8, colony-formation and xenograft mouse models. Epithelial-mesenchymal transition (EMT) and phosphatidylinositide 3-kinases/ protein Kinase B (PI3K/AKT) pathway markers were evaluated by Western blotting. RNA sequencing was used to identify the target of MBD3. Results MBD3 expression was higher in GC tissues and cells than in normal tissues and cells. Additionally, high MBD3 levels were associated with poor prognosis in GC patients. Subsequently, we proved that MBD3 enhanced the migration, invasion and proliferation abilities of GC cells. Moreover, western blot results showed that MBD3 promoted EMT and activated the PI3K/AKT pathway. RNA sequencing analysis showed that MBD3 may increase actin γ1 (ACTG1) expression to promote migration and proliferation in GC cells. Conclusion MBD3 promoted migration, invasion, proliferation and EMT by upregulating ACTG1 via PI3K/AKT signaling activation in GC cells and may be a potential diagnostic and prognostic target.

Nectin-4 is a Ca2+-independent immunoglobulin-like protein that exhibits significantly elevated expression in malignant tumors while maintaining extremely low levels in healthy adult tissues. In recent years, overexpression of Nectin-4 has been implicated in tumor occurrence and development of various cancers, including breast cancer, urothelial cancer, and lung cancer. In 2019, the Food and Drug Administration approved enfortumab vedotin, the first antibody–drug conjugate targeting Nectin-4, for the treatment of urothelial carcinoma. This has emphasized the value of Nectin-4 in tumor targeted therapy and promoted the implementation of more clinical trials of enfortumab vedotin. In addition, many new drugs targeting Nectin-4 for the treatment of malignant tumors have entered clinical trials, with the aim of exploring potential new indications. However, the exact mechanisms by which Nectin-4 affects tumorigenesis and progression are still unclear, and the emergence of drug resistance and treatment-related adverse reactions poses challenges. This article reviews the diagnostic potential, prognostic significance, and molecular role of Nectin-4 in tumors, with a focus on clinical trials in the field of Nectin-4-related tumor treatment and the development of new drugs targeting Nectin-4.

Primary pancreatic lymphoma (PPL) is a rare malignancy, which is defined as a mass centered in pancreas with involvement of contiguous lymph nodes and distant spread may exist. Accurate diagnosis of PPL prior to pathological confirmation remains challenging, underscoring the critical significance of preoperative imaging assessments. This case report collected two instances of PPL that underwent initial evaluation via 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) between August 2021 and July 2022. Correspondingly, pertinent literature encompassing 18F-FDG PET/CT data related to PPL was meticulously reviewed. Including our aforementioned pair of cases, a cumulative total of 25 instances of PPL were assembled. The distinctive profile of 18F-FDG PET/CT images of PPL predominantly manifests as hypermetabolic lesions with diminished density. Primarily characterized by singular lesions and comparatively substantial volumetric dimensions, a total of eleven cases revealed contiguous lymph node engagement, with five instances displaying distant dissemination encompassing lymph nodes in multiple locations. Amongst these, ten patients underwent sequential 18F-FDG PET/CT follow-up post-intervention. In comparison to pancreatic carcinoma, PPL lesions exhibited heightened hypermetabolism, augmented volumetric proportions, and distinct patterns of distant metastasis. This study indicates that the pivotal role of 18F-FDG PET/CT in the diagnosis and assessment of therapeutic efficacy in PPL is unequivocal. Combined with the clinical attributes of patients, the integration of 18F-FDG PET/CT augments the differential diagnostic capacity differentiating PPL from pancreatic carcinoma.

Background: Functional Magnetic Resonance Imaging (fMRI) has shown brain activity alterations in individuals with a history of attempted suicide (SA) who are diagnosed with depression disorder (DD) or bipolar disorder (BD). However, patterns of spontaneous brain activity and their genetic correlations need further investigation. Methods: A voxel-based meta-analysis of 19 studies including 26 datasets, involving 742 patients with a history of SA and 978 controls (both nonsuicidal patients and healthy controls) was conducted. We examined fMRI changes in SA patients and analyzed the association between these changes and gene expression profiles using data from the Allen Human Brain Atlas by partial least squares regression analysis. Results: SA patients demonstrated increased spontaneous brain activity in several brain regions including the bilateral inferior temporal gyrus, hippocampus, fusiform gyrus, and right insula, and decreased activity in areas like the bilateral paracentral lobule and inferior frontal gyrus. Additionally, 5,077 genes were identified, exhibiting expression patterns associated with SA-related fMRI alterations. Functional enrichment analyses demonstrated that these SA-related genes were enriched for biological functions including glutamatergic synapse and mitochondrial structure. Concurrently, specific expression analyses showed that these genes were specifically expressed in the brain tissue, in neurons cells, and during early developmental periods. Conclusion: Our findings suggest a neurobiological basis for fMRI abnormalities in SA patients with DD or BD, potentially guiding future genetic and therapeutic research.

In this paper, we present a novel multi-target feature selection algorithm that incorporates adaptive graph learning and target correlations. Specifically, our proposed approach introduces the low-rank constraint on the regression matrix, allowing us to model both inter-target and input–output relationships within a unified framework. To preserve the similarity structure of the samples and mitigate the influence of noise and outliers, we learn a graph matrix that captures the induced sample similarity. Furthermore, we introduce a manifold regularizer to maintain the global target correlations, ensuring the preservation of the overall target relationship during subsequent learning processes. To solve the final objective function, we also propose an optimization algorithm. Through extensive experiments on eight real-world datasets, we demonstrate that our proposed method outperforms state-of-the-art multi-target feature selection techniques.

Protein tyrosine kinase 6 (PTK6), also known as breast tumor kinase (BRK), serves as a non-receptor intracellular tyrosine kinase within the Src kinases family. Structurally resembling other Src kinases, PTK6 possesses an Src homology 3 (SH3) domain, an Src homology 2 (SH2) domain, and a tyrosine kinase domain (SH1). While considerable efforts have been dedicated to designing PTK6 inhibitors targeting the SH1 domain, which is responsible for kinase activity in various pathways, it has been observed that solely inhibiting the SH1 domain does not effectively suppress PTK6 activity. Subsequent investigations have revealed the involvement of SH2 and SH3 domains in intramolecular and substrate binding interactions, which are crucial for PTK6 function. Consequently, the identification of PTK6 inhibitors targeting not only the SH1 domain but also the SH2 and SH3 domains becomes imperative. Through an in silico structural-based virtual screening approach, incorporating drug repurposing and a consensus docking approach, we have successfully identified four potential ligands capable of concurrently inhibiting the tyrosine kinase domain and SH2/SH3 domains of PT6K simultaneously. This finding suggests potential pathways for therapeutic interventions in PTK6 inhibition.

Objective: Meta-analysis of safety of Olaparib in the treatment of different indications.Methods: The databases of PubMed, The Cochrane Library, EMbase, CNKI, WanFang Data and VIP were searched by computer to collect the research on the indications and the incidence of adverse reactions caused by Olaparib for different cancer types. The search time was from the establishment of the database to May 2022. After two researchers independently screened the literature, extracted the data and evaluated the bias risk included in the study, we used RevMan 5.4 software for meta-analysis.Results: A total of 14 studies were included, with a total sample size of 5119 cases. By meta-analysis, the adverse reactions of Olaparib in the treatment of pancreatic cancer, breast cancer and ovarian cancer were compared. In adverse reactions of any grade, the results showed that fatigue (RR = 1.58, 95% CI [1.20–2.07], p = 0.001) was the most serious in the treatment of pancreatic cancer with Olaparib. Anemia (RR = 2.94, 95% CI [1.97–4.39], p < 0.00001), neutropenia (RR = 1.37, 95% CI [0.80–2.33], p = 0.25), nausea (RR = 1.93, 95% CI [1.61–2.32], p < 0.00001) and vomiting (RR = 1.96, 95% CI [1.59–2.41], p < 0.00001) were the most severe in ovarian cancer. In adverse reactions of grade 3 or above, fatigue (RR = 3.44, 95% CI [1.48–7.98], p = 0.004) and vomiting (RR = 1.09, 95% CI [0.42–2.81], p = 0.86) were the most serious adverse reactions in the treatment of breast cancer with Olaparib. Anemia (RR = 9.74, 95% CI [2.75–34.47], p = 0.0004), neutropenia (RR = 1.33, 95% CI [0.87–2.02], p = 0.19) and nausea (RR = 2.94, 95% CI [1.18–7.32], p = 0.02) were the most severe in ovarian cancer. In addition, the incidence of decreased white blood cell count and hepatotoxicity in the treatment of breast cancer, and the incidence of decreased platelet count, constipation and abdominal pain in the treatment of ovarian cancer were higher than those in pancreatic cancer.Conclusion: Current evidence showed that the risk of adverse reactions of Olaparib in the treatment of different indications is different, and specific analysis and treatment should be carried out for different cancer types. Due to the limitation of the quantity and quality of the included studies, the above conclusions need to be verified by more high-quality studies.

Objective To explore the condiment consumption for restaurant customers in Chinese, and provide basic data for risk assessment of hazards and nutrients in condiment. Methods Weighing method and three-day record method were used to investigate the condiment usage of 126 restaurants in 7 provinces/cities of Beijing, Chongqing, Liaoning, Shandong, Guangdong, Jiangsu and Shaanxi. Meanwhile, the number of people eating in each restaurant every day was recorded to estimate the average consumption. Results The median consumption of condiments per person-time in Chinese restaurants was 3.52 g of salt and substitutes, 1.33 g of flavor enhancer and freshener, 3.63 g of vinegar, 5.18 g of soy sauce, 1.78 g of sauce and its products, 0.25 g of cooking wine and its products,1.54 g of spices, 3.64 g of compound condiments and 0.00 g of other condiments. The difference of condiments consumption among restaurant customers in each province and city was statistically significant(P

A strategy for optimizing the rolling resistance, wet skid and cut resistance of reinforced rubber simultaneously using a supramolecular filler is demonstrated. A β-alanine trimer-grafted Styrene Butadiene Rubber (A3-SBR) pristine polymer was designed and mechanically mixed with commercially available styrene butadiene rubber to help the dispersion of a β-alanine trimer (A3) supramolecular filler in the rubber matrix. To increase the miscibility of A3-SBR with other rubber components during mechanical mixing, the pristine polymer was saturated with ethanol before mixing. The mixture was vulcanized using a conventional rubber processing method. The morphology of the assembles of the A3 supramolecular filler in the rubber matrix was studied by Differential Scanning Calorimetry (DSC) and Transmission Electron Microscopy (TEM). The Differential Scanning Calorimetry study showed that the melting temperature of β-sheet crystals in the vulcanizates was around 179 °C and was broad. The melting temperature was similar to that of the pristine polymer, and the broad melting peak likely suggests that the size of the crystals is not uniform. The Transmission Electron Microscopy study revealed that after mixing the pristine polymer with SBR, some β-sheet crystals were rod-like with several tens of nanometers and some β-sheet crystals were particulate with low aspect ratios. Tensile testing with pre-cut specimens showed that the vulcanizate containing A3-SBR was more cut-resistant than the one that did not contain A3-SBR, especially at a large cut size. The rolling resistance and wet skid were predicted by dynamic mechanical analysis (DMA). DMA tests showed that the vulcanizates containing A3-SBR were significantly less hysteretic at 60 °C and more hysteretic at 0 °C based on loss factor. Overall, the “magic triangle” was expanded by optimizing the rolling resistance, wet-skid, and cut resistance simultaneously using a β-alanine trimer supramolecular filler. The Payne effect also became less severe after introducing the β-alanine trimer supramolecular filler into the system.

Lead poisoning caused by lead pollution seriously affects people's health. Lactic acid bacteria has been shown to be useful for biological scavenging of lead. In this experiment, Sprague-Dawley (SD) rats were treated with 200 mg/L of lead acetate solution daily to induce chronic lead poisoning, and oral Limosilactobacillus fermentum (L. fermentum) SCHY34 to study its mitigation effects and mechanisms on rat neurotoxicity. The L. fermentum SCHY34 showed competent results on in vitro survival rate and the lead ion adsorption rate. Animal experiments showed that L. fermentum SCHY34 maintained the morphology of rat liver, kidney, and hippocampi, reduced the accumulation of lead in the blood, liver, kidney, and brain tissue. Further, L. fermentum SCHY34 alleviated the lead-induced decline in spatial memory and response capacity of SD rats, and also regulated the secretion of neurotransmitters and related enzyme activities in the brain tissue of rats, such as glutamate (Glu), monoamine oxidase (MAO), acetylcholinesterase (AchE), cyclic adenosine monophosphate (cAMP), and adenylate cyclase (AC). In addition, the expression of genes related to cognitive capacity, antioxidation, and anti-apoptotic in rat brain tissues were increased L. fermentum SCHY34 treatment, such as brain-derived neurotrophic factor (BDNF), c-fos, c-jun, superoxide dismutase (SOD)1/2, Nuclear factor erythroid 2-related factor 2 (Nrf2), and B-cell lymphoma 2 (Bcl-2), and so on. L. fermentum SCHY34 showed a great biological scavenging and potential effect on alleviating the toxicity of lead ions.

Abstract Breast cancer, a malignant tumor originating from mammary epithelial tissue, is the most common cancer among women worldwide. Challenges facing the diagnosis and treatment of breast cancer necessitate the search for new mechanisms and drugs to improve outcomes. Estrogen receptor (ER) is considered to be important for determining the diagnosis and treatment strategy. The discovery of the second estrogen receptor, ERβ, provides an opportunity to understand estrogen action. The emergence of ERβ can be traced back to 1996. Over the past 20 years, an increasing body of evidence has implicated the vital effect of ERβ in breast cancer. Although there is controversy among scholars, ERβ is generally thought to have antiproliferative effects in disease progression. This review summarizes available evidence regarding the involvement of ERβ in the clinical treatment and prognosis of breast cancer and describes signaling pathways associated with ERβ. We hope to highlight the potential of ERβ as a therapeutic target.

Objective. To observe the feasibility and safety of rapid rehabilitation nursing in the perioperative period of thoracoscopic treatment of lung cancer patients. Rapid rehabilitation nursing was compared with conventional perioperative nursing to explore its clinical efficacy, i.e., its advantages in improving postoperative comfort, postoperative rehabilitation efficiency, and hospitalization cost of patients undergoing thoracoscopic lung cancer resection. Methods. We carried out a retrospective analysis of 337 lung cancer patients who underwent lobectomy in our thoracic surgery department from July 2019 to June 2021, of which 168 lung cancer patients whose perioperative care method was traditional rehabilitation care were classified as A and 169 lung cancer patients who started to implement the intelligent medical intervention method in the department in September were classified as intelligent medical B. By reviewing patient cases and departmental statistics, general information, length of stay, hospitalization cost, complication rate, pain score, bowel movement recovery time, and pulmonary function index of the two groups A and B were compared. Nursing satisfaction was investigated by using a questionnaire. All the data in the study were processed and analyzed using SPSS 17.0 software. Results. There were no differences in preoperative general data, pathological findings, preoperative underlying diseases, lesion involvement sites, and postoperative TNM stages (P>0.05), which were comparable; the incidence of postoperative pulmonary infection and atelectasis complications, postoperative hospitalization time, and hospitalization cost were lower in group B than in group A; the postoperative chest tube drain placement time was shorter in group B than in group A, and the difference between the two groups was statistically significant (P

Rotavirus (RV) is one of the main pathogens that induce infantile diarrhea and by now no effective drugs are available for RV-induced infantile diarrhea. Thus the development of novel models is of vital importance for the pathological research of RV-induced infantile diarrhea, as well as the progress of the associated treatment strategy. Here we introduced for the first time that RV-Wa strain and RV-SA-11 strain could infect 5 dpf(day post fertilization) and 28 dpf larvae, to induce infantile diarrhea model that was highly consistent with the clinical infection of infants. RV infection significantly changed the signs, survival rate and inflammation of larvae. Some important indicators, including the levels of RV antigen VP4 and VP6, the in vivo RV tracking, and the RV particles were also analyzed, which collectively demonstrated that the model was successfully established. More importantly, we also determined the potentials of the proposed RV-infected zebrafish model for anti-viral drug assessment. In conclusion, we established a RV-infected zebrafish model with formulated relevant indicators both larvae and adult fish, which might be served as a high throughput platform for antiviral drug screening.

Functional constipation, which belongs to the functional gastrointestinal disorder (FGID), is a common disease and significantly impacts daily life. FGID patients have been progressively proven with functional and structural alterations in various brain regions, but whether and how functional constipation affects the brain gray matter volume (GMV) remains unclear; besides, which genes are associated with the GMV changes in functional constipation is largely unknown. On account of the structural MRI image from the 30 functional constipation patients and 30 healthy controls (HCs), GMV analysis showed that functional constipation patients had significantly decreased GMV in the right orbital prefrontal cortex (OFC), left precentral gyrus (PreG), and bilateral thalamus (THA). Correlation analysis showed that the self-rating depressive scale, patient assessment of constipation quality of life (PAC-QOL), and Wexner constipation scores were negatively correlated with GMV of the OFC and negative correlations between PAC-QOL score and GMV of the bilateral THA. Based on the Allen Human Brain Atlas, a cross-sample spatial correlation was conducted and found that 18 genes’ expression values showed robust correlations with GMV changes in functional constipation patients. These outcomes highlight our recognition of the transcriptional features related to GMV changes in functional constipation and could be regarded as candidates to detect biological mechanisms of abnormality in functional constipation patients.

Accurately considering the dynamic mechanical properties of rolled thin-walled steel plates (TWSPs) under low and medium strain rates is the basis of numerical simulations of W-beam guardrails subjected to vehicle impact. Uniaxial tensile tests were conducted on specimens extracted from different locations (flat TWSPs without cold rolling treatment, and the cross-sectional centers and slopes of rolled TWSPs) and under different strain rates (ε˙ = 0.00025, 0.01, and 50 s−1). Based on experimental and numerical results, the cross-sectional center of a rolled TWSP is recommended as the representative sampling location for uniaxial tensile tests. Additional uniaxial tensile tests with wider strain rates of 10, 100, and 200 s−1 were also conducted on specimens at the recommended sampling location (cross-sectional center) of rolled TWSPs. It was found that the Cowper–Symonds model with parameters of C = 40 s−1 and p = 5 recommend by Symonds significantly overestimated the strain rate effects of the rolled TWSP material in the low and medium strain-rate region. The model with calibrated parameters of C = 4814 s−1 and p = 2.9 was recommended for considering the influences of strain rate effects on the dynamic mechanical properties of rolled TWSP at low to medium strain rates.

Gastrointestinal (GI) tract graft-versus-host disease (GvHD) is a major cause of post-allo-HSCT (hematopoietic stem cell transplantation) morbidity and mortality. Patients with steroid-refractory GI-GvHD have a poor prognosis and limited therapeutic options. FMT2017002 trial (#NCT03148743) was a non-randomized, open-label, phase I/II clinical study of FMT for treating patients with grade IV steroid-refractory GI-GvHD. A total of 55 patients with steroid-refractory GI-GvHD were enrolled in this study. Forty-one patients with grade IV steroid-refractory GI-GvHD were included in the final statistical analysis. Of them, 23 patients and 18 patients were assigned to the FMT group and the control group, respectively. On days 14 and 21 after FMT, clinical remission was significantly greater in the FMT group than in the control group. Within a follow-up period of 90 days, the FMT group showed a better overall survival (OS). At the end of the study, the median survival time was >539 days in the FMT group and 107 days in the control group (HR=3.51; 95% CI, 1.21–10.17; p=0.021). Both the event-free survival time (EFS) (HR=2.3, 95% CI, 0.99–5.4; p=0.08) and OS (HR=4.4, 95% CI, 1.5–13.04; p=0.008) were higher in the FMT group during the follow-up period. Overall, the mortality rate was lower in the FMT group (HR=3.97; 95% CI, 1.34–11.75; p=0.013). No differences in the occurrence of any other side effects were observed. Our data suggest that the diversity of the intestinal microbiota could be affected by allo-HSCT. Although its effectiveness and safety need further evaluation, FMT may serve as a therapeutic option for grade IV steroid-refractory GI-GvHD.Clinical Trial Registration[ClinicalTrials.gov], identifier [NCT03148743].

When thermoplastic resin-toughened carbon fiber (CF) composites are formed by liquid resin transfer molding (RTM), the conventional methods cannot be used to set the fabric preform, which affects the overall mechanical properties of the composites. To address this challenge, the benzoxazine-based tackifier BT5501A was designed, a preforming–toughening bifunctional CF fabric was fabricated by employing thermoplastic polyaryletherketone (PEK-C), and an aviation RTM-grade bismaleimide (BMI) resin was used as the matrix to study the effect of the benzoxazine-based tackifier on the thermal curing property and heat resistance of the resin matrix. Furthermore, the preforming and toughening effects on the bifunctional CF fabric reinforced the BMI resin composites. The tackifier BT5501A has good process operability. The application of this tackifier can advance the thermal curing temperature of the BMI resin matrix and decrease the glass transition temperature of the resin, compared to that of the pure BMI resin. Furthermore, when the tackifier was added into the CF/PEK-C/BMI composites, the obtained CF/BT5501A/PEK-C/BMI composites had comparable compression strength after impact, pit depth, and damage area, compared to the CF/PEK-C/BMI composites, while the tackifier endowed the fabric preform with an excellent preforming effect.

Genistein (Gen), a kind of natural isoflavone drug monomer with poor water solubility and low oral absorption, was incorporated into oral nanoparticles with a new mesoporous carrier material, NH2-MCM-41, which was synthesized by copolycondensation. When the ratio of Gen to NH2-MCM-41 was 1:0.5, the maximum adsorption capacity of Gen was 13.15%, the maximum drug loading was 12.65%, and the particle size of the whole core–shell structure was in the range of 370 nm–390 nm. The particles were characterized by a Malvern particle size scanning machine, XRD, Fourier transform infrared spectroscopy, scanning electron microscopy, and nitrogen adsorption and desorption. Finally, Gen-NH2-MCM-41 was encapsulated by sodium alginate (SA), and the chimerism of this material, denoted as GEN-NH2-MCM-41@SA, was investigated. In vitro release experiments showed that, after 5 h in artificial colon fluid (pH = 8.0), the cumulative release reached 99.56%. In addition, its anti-rotavirus (RV) effect showed that the maximum inhibition rate was 62.24% at a concentration of 30 μM in RV-infected Caco-2 cells, and it significantly reduced the diarrhea rate and diarrhea index in an RV-infected-neonatal mice model at a dose of 0.3 mg/g, which was better than the results of Gen. Ultimately, Gen-NH2-MCM-41@SA was successfully prepared, which solves the problems of low solubility and poor absorption and provides an experimental basis for the application of Gen in the clinical treatment of RV infection.

The effects of lead as a dietary pollutant remain a global public health concern that needs urgent resolution. Children are highly susceptible to the adverse outcomes of lead pollution, as even low levels of lead may cause irreversible damage to intellectual development. Since several sources of lead exposure are present in the environment, it is necessary to identify the attributable burden of lead-related diseases arising from different exposure sources. In the present study, we used epidemiological data from studies around the nation to estimate the burden of mild intellectual disability (MID) attributed to lead exposure sources by using disability-adjusted life years (DALYs). To this end, a dose-response approach was used and a model comprising three components was established: exposure, dose-response, and DALYs module. In Chinese children aged 0–6 years, blood lead levels (BLLs) of 5.34 ± 3.09 μg/dL resulted in a MID incidence rate of 12.84 cases per 1000 children, with an estimated burden of disease (BoD) of 42.23 DALYs per 1000 children. Owing to dietary lead exposure, 36.64 healthy life years per 1000 children were lost, which was notably higher than the outcomes associated with exposure from other sources. This was consistent with the result that dietary exposure was the main contributor to children’s lead exposure, accounting for 86.76%. According to the regional distribution based on the existing literature, the areas in China with higher BLLs were Heilongjiang, Shanxi, and Jiangxi. Our findings provided the information for lead risk management decisions and policies making. Keywords: Lead, Children, Diet, MID, BoD

Haspin, an atypical serine/threonine protein kinase, is a potential target for cancer therapy. 5-iodotubercidin (5-iTU), an adenosine derivative, has been identified as a potent Haspin inhibitor in vitro. In this paper, quantum chemical calculations and molecular dynamics (MD) simulations were employed to identify and quantitatively confirm the presence of halogen bonding (XB), specifically halogen∙∙∙π (aromatic) interaction between halogenated tubercidin ligands with Haspin. Consistent with previous theoretical finding, the site specificity of the XB binding over the ortho-carbon is identified in all cases. A systematic increase of the interaction energy down Group 17, based on both quantum chemical and MD results, supports the important role of halogen bonding in this series of inhibitors. The observed trend is consistent with the experimental observation of the trend of activity within the halogenated tubercidin ligands (F < Cl < Br < I). Furthermore, non-covalent interaction (NCI) plots show that cooperative non-covalent interactions, namely, hydrogen and halogen bonds, contribute to the binding of tubercidin ligands toward Haspin. The understanding of the role of halogen bonding interaction in the ligand–protein complexes may shed light on rational design of potent ligands in the future.

A certain type of engineering environmental management information system (referred to as the system) has been developed for many years, but there are not many construction cases. Domestic and foreign companies and enterprises have little research on this type of engineering system construction plan, and the knowledge base of historical experience and lessons is less. The design analysis of the engineering system construction scheme has practical significance and value. The system construction design adopts large-scale joint control technology to integrate all environmental protection subsystems into an organic whole, realize information sharing and collaborative work, realize remote monitoring and control of process equipment, and realize dynamic and online management of equipment information. Eventually, a certain type of engineering achieve the goals of intelligent control, unmanned duty, and controllable operation.

Transamidation reactions are kinetically and thermodynamically challenging because of the stability of the amide starting materials. Here, the authors show a two-step process—activation of a secondary amide, followed by nickel-catalysed C–N bond cleavage—that allows mild and high yielding transamidation.

With ever-increasing concerns on health and environmental safety, there is a fast-growing interest in new technologies for medical devices and applications. Particularly, wireless power transfer (WPT) technology provides reliable and convenient power charging for implant medical devices without additional surgery. For those WPT medical systems, the width of the human body restricts the charging distance, while the specific absorption rate (SAR) standard limits the intensity of the electromagnetic field. In order to develop a high-efficient charging strategy for medical implants, the key factors of transmission distance, coil structure, resonant frequency, etc. are paid special attention. In this paper, a comprehensive overview of near-field WPT technologies in medical devices is presented and discussed. Also, future development is discussed for the prediction of different devices when embedded in various locations of the human body. Moreover, the key issues including power transfer efficiency and output power are addressed and analyzed. All concerning characteristics of WPT links for medical usage are elaborated and discussed. Thus, this review provides an in-depth investigation and the whole map for WPT technologies applied in medical applications.

Diffusion kurtosis imaging (DKI) is an extension of diffusion tensor imaging (DTI), exhibiting improved sensitivity and specificity in detecting developmental and pathological changes in neural tissues. However, little attention was paid to the performances of DKI and DTI in detecting white matter abnormality in schizophrenia. In this study, DKI and DTI were performed in 94 schizophrenia patients and 91 sex- and age-matched healthy controls. White matter integrity was assessed by fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), mean kurtosis (MK), axial kurtosis (AK) and radial kurtosis (RK) of DKI and FA, MD, AD and RD of DTI. Group differences in these parameters were compared using tract-based spatial statistics (TBSS) (P AK (20%) > RK (3%) and RD (37%) > FA (24%) > MD (21%) for DKI, and RD (43%) > FA (30%) > MD (21%) for DTI. DKI-derived diffusion parameters (RD, FA and MD) were sensitive to detect abnormality in white matter regions (the corpus callosum and anterior limb of internal capsule) with coherent fiber arrangement; however, the kurtosis parameters (MK and AK) were sensitive to reveal abnormality in white matter regions (the juxtacortical white matter and corona radiata) with complex fiber arrangement. In schizophrenia, the decreased AK suggests axonal damage; however, the increased RD indicates myelin impairment. These findings suggest that diffusion and kurtosis parameters could provide complementary information and they should be jointly used to reveal pathological changes in schizophrenia.

Although extensive resting-state functional connectivity (rsFC) changes have been reported in schizophrenia, rsFC changes of the frontal pole (FP) remain unclear. The FP contains several subregions with different connection patterns; however, it is unknown whether the FP subregions are differentially affected in schizophrenia. To explore this possibility, we compared rsFC differences of the FP subregions between schizophrenia patients and healthy controls.One hundred healthy controls and 91 patients with schizophrenia underwent resting-state functional MRI with a sensitivity-encoded spiral-in (SENSE-SPIRAL) imaging sequence to reduced susceptibility-induced signal loss and distortion. The FP was subdivided into the orbital (FPo), medial (FPm), and lateral (FPl) subregions. Mean fMRI time series were extracted for each FP subregion and entered into a seed-based rsFC analysis.The FP subregions exhibited differential rsFC patterns in both healthy controls and schizophrenia patients. Direct comparison between groups revealed reduced rsFCs between the bilateral FPl and several cognitive-related regions, including the dorsolateral prefrontal cortex, medial prefrontal cortex, anterior cingulate cortex, posterior cingulate cortex/precuneus, temporal cortex and inferior parietal lobule in schizophrenia. Although the FPl exhibited obvious atrophy, rsFC changes were unrelated to volumetric atrophy in the FPl, to duration of illness, and to antipsychotic medication dosage. No significant differences were observed in the rsFCs of other FP subregions.These findings suggest a selective (the lateral subregion) functional disconnection of the FP subregions in schizophrenia.