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Background: Esophageal cancer (EC), including esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC), is a highly prevalent malignancy that occurs predominantly in the Asian region and is related to ethnicity, genetics, diet, and lifestyle. The nuclear receptor (NR) superfamily consists of 48 members of the human body. It is a collection of a large class of transcription factors, including Peroxisome proliferator-activated receptors (PPARs), Farnesol X receptor (FXR), Vitamin D receptor (VDR), Retinoic acid receptor (RAR), Pregnane X receptor (PXR), Androgen receptor (AR) and so on. Several NRs have been detected as oncogenes or tumor suppressors in EC progression. Objectives: NRs are associated with the progression of many cancers, including EC. Some NRs, such as PPARs and FXR, play an important role in EC. Studying the molecular mechanism of NRs in EC is helpful for further understanding the development of EC. Preclinical research and development of small molecule compound drugs targeting NRs have provided new ideas for the potential targeted therapy of EC. Methods: This review summarizes the studies on NRs in EC in recent years, mainly including in vitro cell experiments and in vivo animal experiments. Results: NRs influence EC progress in a variety of ways. They mainly affect the proliferation, migration and drug resistance of EC cells by affecting key cancer cell signaling pathways. Activation or inhibition of NRs inhibits or promotes EC progression, depending on EC types and tumor stages. Preclinical studies mainly focus on the development of small molecule drugs for targeting NRs (such as PPARγ agonists, PPARδ inhibitors, and FXR agonists), and agonists or inhibitors of NRs will become a potential therapeutic regimen for EC. Conclusion: The studies on the roles of NRs in EC have provided a theoretical basis for us to further understand the pathogenesis of EC and develop potential therapeutic drugs targeting NRs for the treatment of different diseases.

Cranes are widely employed for transportation in many industrial fields. However, strong couplings and high nonlinearities increase difficulty of designing effective control methods for crane systems. Additionally, complex environments may bring uncertainties and unfavorable factors for the control problem. In this paper, we design an effective tracking approach for double pendulum cranes considering variable rope lengths problem by using sliding mode technique, to further improve the robustness and achieve the control objectives of accurate tracking, while effective suppression for double pendulum swing is also ensured. We design a proper sliding mode surface containing all state variables, which effectively suppresses swing angles of the payload and the hook. Then, the time delay estimator technique is used to estimate parameter uncertainty-related terms and the estimation errors are effectively tackled by using sliding mode technique. The effectiveness is rigorously proved by Lyapunov stability theory. At last, comprehensive simulations are implemented to show the proper performance.

Ying Cao,1,&ast; Heng Zhang,2,&ast; Gui-Lan Tu,3 Ye Tian,2 Xiao-Hu Tang,2 Lei Tang,1 Mu-Xia Luo,1 Yan-Dong Wang,2 Zhen Wang,2 Shu-Jie Xia,4 Guang-Heng Luo2 1Guizhou University Medical College, Guiyang, 550025, People’s Republic of China; 2Department of Urology, Guizhou Provincial People’s Hospital, Guiyang, 550002, People’s Republic of China; 3Department of Pathology, Guizhou Provincial People’s Hospital, Guiyang, 550002, People’s Republic of China; 4Department of Urology, Shanghai First People’s Hospital, Shanghai Jiaotong University, Shanghai, 200080, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guang-Heng Luo, Email luoguangheng1975@126.comObjective: The aim of the present study was to observe the effect of the stroma proportion in hyperplasia nodules on the clinical symptoms of benign prostatic hyperplasia (BPH) patients and to identify the different genes and pathways in prostatic hyperplasia nodules between patients with epithelial-dominated hyperplasia (EDH) and stromal-dominated hyperplasia (SDH) nodules.Methods: Sixty-seven BPH patient samples underwent transurethral resection of the prostate (TURP) were collected and retrospectively analyzed. The differences in clinical parameters between the EDH and SDH groups were investigated. Collagen fiber percentage was assessed, and the correlation with clinical parameters was evaluated. mRNA sequencing in hyperplasia nodules of 8 BPH patients was performed, and differentially expressed genes (DEGs) between the EDH and SDH groups were screened. These DEGs were analyzed using GO, KEGG and PPI analysis.Results: The results showed the IPSS was significantly higher in the SDH group than in the EDH group (p < 0.01). The collagen fiber percentage of BPH nodules was higher in the SDH group than in the EDH group (p < 0.05), and the collagen fiber percentage was positively correlated with the IPSS (r = 0.4058, p = 0.0007). A total of 172 DEGs were obtained, including 63 up-regulated genes and 109 down-regulated genes. GO and KEGG pathway enrichment analyses showed DEGs were mainly enriched in extracellular matrix structural constituents. The top 10 hub genes were associated to the components of extracellular matrix and fibrosis.Conclusion: These results suggested that the symptoms of BPH patients with SDH nodules may be associated with prostate fibrosis and fibrosis may be a significant contributing factor in BPH/LUTS patients with SDH nodules.Keywords: benign prostate hyperplasia, lower urinary tract symptoms, prostate fibrosis, stroma, pathology

Porcine reproductive and respiratory syndrome virus (PRRSV)-1 and PRRSV-2 have long been cocirculating in China. To date, all PRRSV-1 strains in China have been classified as subtype 1. We investigated the prevalence of PRRSV-1 in several areas of China from 2016 to 2022 and found that BJEU06-1-like strains comprised the main epidemic branch of PRRSV-1. Pathogenicity data for this subgroup are currently lacking. In this study, the Chinese BJEU06-1-like PRRSV-1 strain ZD-1 was isolated from primary alveolar macrophages (PAMs). ZD-1 has undergone no recombination and has a 5-aa discontinuous deletion in the Nsp2 protein, similar to other BJEU06-1-like strains; additionally, ZD-1 has a 26 aa C-terminal truncation in the GP3 gene. Pathogenicity studies revealed that ZD-1 causes obvious clinical symptoms: prolonged fever; reduced body weight; alveolar epithelial proliferation and moderate alveolar diaphragm widening in the lungs; diffuse lymphocytic hyperplasia in the lymph nodes; high levels of viremia in the serum; and elevated viral loads in the lungs, lymph nodes, and tonsils. These results suggested that the BJEU06-1-like PRRSV-1 strain ZD-1 is moderately pathogenic to piglets. This is the first study to evaluate the pathogenicity of the BJEU06-1-like branch in China, enriching the understanding of PRRSV-1 in China.

Over the course of chronic drug use, brain transcriptional neuroadaptation is thought to contribute to a change in drug use behavior over time. The function of the transcription factor CREB (cAMP response element binding protein) within the nucleus accumbens (NAc) has been well documented in opposing the rewarding properties of many classes of drugs, yet the gene targets through which CREB causally manifests these lasting neuroadaptations remain unknown. Here, we identify zinc finger protein 189 (Zfp189) as a CREB target gene that is transcriptionally responsive to acute and chronic cocaine use within the NAc of mice.To investigate the role of the CREB-Zfp189 interaction in cocaine use, we virally delivered modified clustered regularly interspaced short palindromic repeats (CRISPR)/dCas9 constructs capable of selectively localizing CREB to the Zfp189 gene promoter in the NAc of mice.We observed that CREB binding to the Zfp189 promoter increased Zfp189 expression and diminished the reinforcing responses to cocaine. Furthermore, we showed that NAc Zfp189 expression increased within D1 medium spiny neurons in response to acute cocaine but increased in both D1- and D2-expressing medium spiny neurons in response to chronic cocaine. CREB-mediated induction of Zfp189 potentiated electrophysiological activity of D1- and D2-expressing medium spiny neurons, recapitulating the known effect of CREB on these neurons. Finally, targeting CREB to the Zfp189 promoter within NAc Drd2-expressing neurons, but not Drd1-expressing neurons, was sufficient to diminish cocaine-conditioned behaviors.Together, these findings point to the CREB-Zfp189 interaction within the NAc Drd2+ neurons as a molecular signature of chronic cocaine use that is causal in counteracting the reinforcing effects of cocaine.

Synthesis of the C19-truncated maltepolide E has been accomplished via a diene–ene RCM strategy without damage to the C11–C14 alkenyl epoxy unit. Upon release of the C17-OH group, it attacked at the C14 position with double bond migration and epoxide ring-opening to furnish the C19-truncated maltepolide A and B as proposed for the biosynthesis of maltepolides. Preliminary cytotoxicity data of the synthesized C19-truncated maltepolides against L929 mouse fibroblast cell line suggest irrelevance of the vinyl epoxide and importance of the conjugated dienyl keto unit for the observed anticancer activity.

Bullying is a growing concern worldwide. However, there is insufficient research on the prevalence and factors associated with different forms of bullying in a large sample of Chinese adolescents. This study aims to investigate the prevalence and associated factors of bullying victimization among Chinese high school students.Data from the 2020-2021 cross-sectional survey of the DYH program were used. A total of 8203 high school students were randomly selected from all 17 cities in Shandong Province, China. Bullying victimization was measured using two separate questions and identified into three types: school bullying victims, cyberbullying victims, and combined bullying victims. The multinomial logit model was used to explore the factors related to bullying victimization.The prevalence of bullying victimization was 11.59 %, with 4.04 % of school bullying, 3.37 % of cyberbullying, and 4.18 % of combined bullying. Smoking was negatively associated with bullying victimizations. Male, physical exercise, peer relationships, and obsessive-compulsive symptoms were significantly associated with school bullying victims and combined victims. Watching TV was an influencing factor for school bullying victims and cyberbullying victims. Single-child households, family economic status, drinking alcohol, parent-child relationships, and paranoia were correlated with different types of bullying victimization.The cross-sectional design limited the examination of causal inferences.We should pay more attention to cyberbullying victimization, which has become as common as school bullying victimization among high school students. The associated factors explored in this study may contribute to understanding bullying victimizations and designing bullying intervention strategies among high school students in China.

The changed phenolic acids (PAs) allelochemicals exuded by the roots induced by interspecific interactions is related to intercropping alleviates soil-borne disease. However, the presence of PAs in roots and root exudations and their rhizodeposition under intercropping are still unclear. Hydroponic and soil experiments of wheat, faba bean, and wheat intercropped with faba bean were conducted, and the major compositions and contents of PAs in roots, root exudations, and rhizospheric soil were determined. The results showed that ρ-hydroxybenzoic, vanillic, and syringic acids were the major components of PAs in roots, root exudations, and rhizospheric soil in a wheat and faba bean intercropping system. The compositions and percentages of PAs in roots of faba bean were altered when faba bean intercropped with wheat. The total exudation rate of PAs in root exudations was decreased by 30%–60% under the wheat and faba bean intercropping (W//F) system as compared to mono-cropped faba bean (MF). ρ-hydroxybenzoic acid was identified in the root exudation of both MF and mono-cropped wheat (MW), but not detected in the intercropping on 60 days after transplanting. Vanillic acid was only detected in the root exudation of MF on 30 days after transplanting. The rhizodepostion of vanillic and cumaric acid were decreased at both branching and pod setting stages in W//F as compared to MF. In conclusion, interspecific interaction changed the compositions and contents of PAs in faba bean roots and root exudations. W//F constrained vanillic acid exuded by roots and decreased vanillic and coumaric acid rhizodeposition by faba bean, which provides insight into root-soil interactions in the intercropping systems.

Delta(9)-tetrahydrocannabinolic acid (THCA) and delta(9)-tetrahydrocannabivarin (THCV) are phytocannabinoids with a similar structure derived from Cannabis sativa and possess a variety of biological activities. However, the relationship between the metabolic characterisation and bioactivity of THCA and THCV remains elusive.To explore the relationship between the metabolism of THCA and THCV and their underlying mechanism of activity, human/mouse liver microsomes and mouse primary hepatocytes were used to compare the metabolic maps between THCA and THCV through comparative metabolomics. A total of 29 metabolites were identified containing 7 previously undescribed THCA metabolites and 10 previously undescribed THCV metabolites. Of these metabolites, THCA was transformed into an active metabolite of delta(9)-tetrahydrocannabinol (THC) in these three systems, while THCV was transformed into THC and CBD.Bioactivity assays indicated that all of these phytocannabinoids exhibited anti-inflammatory activity, but the effects of THCA and THCV were slightly different in macrophages RAW264.7. Prediction of ADMET lab demonstrated that THCV and its metabolites were endowed with the advantage of blood–brain barrier (BBB) penetration compared to THCA.In conclusion, this study highlighted that metabolism plays a critical role in the biological activity of phytocannabinoids. Delta(9)-tetrahydrocannabinolic acid (THCA) and delta(9)-tetrahydrocannabivarin (THCV) are phytocannabinoids with a similar structure derived from Cannabis sativa and possess a variety of biological activities. However, the relationship between the metabolic characterisation and bioactivity of THCA and THCV remains elusive. To explore the relationship between the metabolism of THCA and THCV and their underlying mechanism of activity, human/mouse liver microsomes and mouse primary hepatocytes were used to compare the metabolic maps between THCA and THCV through comparative metabolomics. A total of 29 metabolites were identified containing 7 previously undescribed THCA metabolites and 10 previously undescribed THCV metabolites. Of these metabolites, THCA was transformed into an active metabolite of delta(9)-tetrahydrocannabinol (THC) in these three systems, while THCV was transformed into THC and CBD. Bioactivity assays indicated that all of these phytocannabinoids exhibited anti-inflammatory activity, but the effects of THCA and THCV were slightly different in macrophages RAW264.7. Prediction of ADMET lab demonstrated that THCV and its metabolites were endowed with the advantage of blood–brain barrier (BBB) penetration compared to THCA. In conclusion, this study highlighted that metabolism plays a critical role in the biological activity of phytocannabinoids.

A low-content SnO2 nanodot/N-rGO composite is prepared via a distinctive lattice confinement and delivers satisfactory lithium/sodium storage, due to its high capacitive contribution, as well as low electronic and ionic diffusion resistance.

I2-mediated catabolism and reconstruction of amino acids emerges again to furnish 2-aroyl-3-arylquinolines in a convenient way.

Strain leads to a rich magnetic phase transition in PC3NR, that is, from bandgap-tunable bipolar magnetic semiconductors to spin-gapless semiconductors to ferromagnetic metals or half-metal magnets and ±100% SP over a wide energy interval around EF.

The complex process of wound healing depends on the coordinated interaction between various immunological and biological systems, which can be aided by technology. This present review provides a broad overview of the medical applications of piezoelectric and triboelectric nanogenerators, focusing on their role in the development of wound healing technology. Based on the finding that the damaged epithelial layer of the wound generates an endogenous bioelectric field to regulate the wound healing process, development of technological device for providing an exogenous electric field has therefore been paid attention. Authors of this review focus on the design and application of piezoelectric and triboelectric materials to manufacture self-powered nanogenerators, and conclude with an outlook on the current challenges and future potential in meeting medical needs and commercialization., Grpahical Abstract

The Coma Recovery Scale-Revised (CRS-R) is the gold standard behavioral assessment scale for diagnosis of patients with disorders of consciousness (DOC). The reliability of CRS-R in monitoring the state of consciousness is well established. It is widely used by experts working in the fields of DOC. However, it is complex, time-consuming and difficult to use by non-professionals. Hence, it is imperative to simplify the evaluation to ease clinical workflow and increase work efficiency. In this study we evaluated the accuracy of a simplified scale using only 8 most commonly observed behaviors from the standard 29-item CRS-R scale. To assess the diagnostic accuracy of the simplified evaluation process of CRS-R compared to the standard CRS-R, a total of 150 patients with DOC who were admitted to the Hospital of Zhejiang People's Armed Police between February 2020 and September 2021 were screened in a prospective, observational study. Two trained clinicians used the CRS-R and the simplified CRS-R to evaluate the consciousness level of the enrolled patients, respectively. SPSS 23 was used for statistical analysis. Weighted kappa was used to demonstrate the level of agreement between the two methods. A p-value 0.01 was considered to be statistically significant. Kappa coefficient was 0.952 (95 % CI: 0.905-0.999, p 0.01), which indicated that the difference was statistically significant, thereby suggesting satisfactory level of agreement between the diagnostic outcomes of the CRS-R and simplified CRS-R. The simplified CRS-R could determine the state of consciousness of patients with ease and high accuracy.

Intestinal electrical stimulation (IES) has been proposed for treating diabetes; however, its parameters need to be further systematically optimized. This study aimed to optimize the parameters of IES and investigate its possible mechanisms involving glucagon-like peptide-1 (GLP-1) in diabetic rats.Thirty-six high-fat diet-induced diabetic rats were chronically implanted with a pair of bipolar electrodes at the duodenum for IES. The oral glucose tolerance test (OGTT) was performed in a number of sessions with IES using different parameters and biphasic charge-balanced waveforms to derive the best values for train on-time, pulse frequency, and pulse width. Incretin hormones such as GLP-1 were assessed and the GLP-1 antagonist Exendin 9-39 was used to assess the role of GLP-1 in the ameliorating effect of IES on hyperglycemia.The most effective IES parameters in reducing blood glucose (BG) during the OGTT were derived: 1.2 sec on, 0.3 sec off, 80 Hz, 3 msec. IES with these parameters reduced BG level by at least 29% from 15 min to 180 min (p 0.05 for all points, N = 10). IES with these stimulation parameters increased plasma GLP-1 level at 30 min, 60 min, 90 min and gastric inhibitory peptide (GIP) level at 30 min (N = 8). Exendin 9-39 blocked the inhibitory effect of IES on BG (p 0.05, IES + Exendin 9-39 vs sham-IES, N = 8).IES with the most effective parameters derived in this study improves hyperglycemia in diabetic rats. The ameliorating effect of IES on hyperglycemia is attributed to the enhanced release of GLP-1. IES has great potential for treating diabetes.

Genetic predisposition and disruption of host gut microbiota and immune system can result in inflammatory bowel disease (IBD). Here, we show that miRNA-149-5p (miR-149-5p) and miRNA-149-3p (miR-149-3p) play crucial roles in IBD. Mice lacking miR-149-3p were considerably more susceptible to dextran sulfate sodium (DSS)-induced colitis than wild-type (WT) mice, accompanied by more serious inflammatory symptoms and increased gene expression of certain inflammatory cytokines. Both miR-149-5p and miR-149-3p suppressed colon inflammatory response

A review is provided of various approaches that have been adopted recently to assess the fatigue of ships and offshore structures. The relevant fatigue loading is reviewed first, focusing on the successive loading and unloading of the cargo and the transient loadings. The factors influencing fatigue strength are discussed, including the geometrical parameters, material, residual stress, and ones related to the environment. Different approaches for fatigue analyses of seam-welded joints are covered, i.e., the structural stress or strain approach, the notch stress or strain approach, notch intensity approach, and the crack propagation approach.

Financial inclusion and Fintech have revolutionized the financial sector and fundamentally changed how we store, save, borrow, transfer, and invest money. This paper investigates the impact of financial inclusion and Fintech on income inequality using waves of survey data for 2011, 2014, and 2017 across 39 African countries. By using pooled ordinary least square and two-stage least square (2sls) estimation methods, we obtain three key findings. First, institutional factors such as political stability, control of corruption, and government effectiveness determine Fintech and financial inclusion. Second, Fintech encourages individuals to have a formal bank account, thereby promoting financial inclusion. Third, financial inclusion and Fintech exacerbate income inequality. The direct implication of our findings is that policymakers make tradeoffs whether they seek to achieve higher inclusion and Fintech or to reduce income inequality. We highlight that a pro-poor financial sector development is vital. Easing the bottleneck in obtaining loans, offering agriculture-based Fintech services, and improving digital literacy are important steps to gain the most out of inclusion and Fintech in reducing income inequality.