Capturing acyl-enzyme intermediates with genetically encoded 2,3-diaminopropionic acid for hydrolase substrate identification.

Catalytic mechanism-based, light-activated traps have recently been developed to identify the substrates of cysteine or serine hydrolases. These traps are hydrolase mutants whose catalytic cysteine or serine are replaced with genetically encoded 2,3-diaminopropionic acid (DAP). DAP-containing hydrolases specifically capture the transient thioester- or ester-linked acyl-enzyme intermediates resulting from the first step of the proteolytic reaction as their stable amide analogs. The trapped substrate fragments allow the downstream identification of hydrolase substrates by mass spectrometry and immunoblotting. In this protocol, we provide a detailed step-by-step guide for substrate capture and identification of the peptidase domain of the large tegument protein deneddylase (UL36USP) from human herpesvirus 1, both in mammalian cell lysate and live mammalian cells. Four procedures are included: Procedure 1, DAP-mediated substrate trapping in mammalian cell lysate (~8 d); Procedure 2, DAP-mediated substrate trapping in adherent mammalian cells (~6 d); Procedure 3, DAP-mediated substrate trapping in suspension mammalian cells (~5 d); and Procedure 4, substrate identification and validation (~12-13 d). Basic skills to perform protein expression in bacteria or mammalian cells, affinity enrichment and proteomic analysis are required to implement the protocol. This protocol will be a practical guide for identifying substrates of serine or cysteine hydrolases either in a complex mixture, where genetic manipulation is challenging, or in live cells such as bacteria, yeasts and mammalian cells.

Differentiation of bone marrow mesenchymal stem cells into Leydig-like cells with testicular extract liquid in vitro.

Differentiation of Leydig cells plays a key role in male reproductive function. Bone marrow mesenchymal stem cells (BMSCs) have emerged as a potential cell source for generating Leydig-like cells due to their multipotent differentiation capacity and accessibility. This study aimed to investigate the morphological and genetic expression changes of BMSCs during differentiation into Leydig-like cells. Testicular extract liquid, which simulates the microenvironment in vivo, induced the third passage BMSCs differentiated into Leydig-like cells. Changes in cell morphology were observed by microscopy, the formation of lipid droplets of androgen precursor was identified by Oil Red Staining, and the expression of testicular specific genes 3ß-HSD and SF-1 in testicular stromal cells was detected by RT-qPCR. BMSCs isolated from the bone marrow of Sprague-Dawley (SD) rats were cultured for 3 generations and identified as qualified BMSCs in terms of morphology and cell surface markers. After 14 days of induction with testicular tissue lysate, lipid droplets appeared in the cytoplasm of P3 BMSCs by Oil Red O staining. RT-qPCR detection was performed on BMSCs on the 3rd, 7th, 14th, and 21st day after induction. Relative expression levels of 3ß-HSD mRNA significantly increased after 14 days of induction, while the relative expression of SF-1 mRNA increased after 14 days of induction but was not significant. BMSCs can differentiate into testicular interstitial cells with reserve androgen precursor lipid droplets after induction by testicular tissue lysate. The differentiation ability of BMSCs provides the potential to reconstruct the testicular microenvironment and is expected to fundamentally improve testicular function and provide new treatment options for abnormal spermatogenesis diseases.

Establishing a carcinoembryonic antigen-associated competitive endogenous RNA network and forecasting an important regulatory axis in colon adenocarcinoma patients.

Background: Colorectal cancer is one of the top five malignant tumors in the world in terms of morbidity and mortality. Numerous long non-coding RNAs (lncRNAs) are specifically expressed in tumours and can affect various types of human cancer by participating in competitive endogenous RNA (ceRNA) regulatory networks. However, the specific mechanisms and complex networks of ceRNA regulatory patterns in colon adenocarcinoma (COAD) remain unclear. Methods: Using The Cancer Genome Atlas (TCGA) database, we identified the differentially expressed lncRNA, microRNA (miRNA), and messenger RNA (mRNA) between colon cancer and normal tissues, as well as between groups with high and low CEACAM5 expression. Then, we constructed CEACAM5-related ceRNA networks, established the key lncRNA-miRNA-mRNA regulatory axis, and explored the biological mechanisms of this axis and its clinical significance in colon cancer from multiomic aspects. Results: We constructed a ceRNA network of 18 lncRNAs, 177 miRNAs, and 25 mRNAs associated with CEACAM5 and finally established the key LCMT1-AS2/miR-454-3p/ribosomal protein S6 kinase A5 (RPS6KA5) axis associated with overall survival. Subsequent investigations have indicated that this regulatory axis could potentially participate in the progression of COAD and exert influence on the therapeutic outcomes of chemotherapy and immunotherapy. It may be involved in the PI3K-Akt signaling pathway and may modify the tumor immune microenvironment and influence the course of COAD. Additionally, it may be related to ferroptosis, N6-methyladenosine (m6A) methylation, and tumor stemness and interfere with the sensitivity of tumor cells to 5-fluorouracil and immunotherapy. Conclusions: The LCMT1-AS2/RPS6KA5 axis may be instrumental in tumor progression, potentially acting as a prognostic biomarker and therapeutic target.

A single-cell atlas of immunocytes in the spleen of a mouse model of Wiskott-Aldrich syndrome.

Wiskott-Aldrich syndrome (WAS) is a disorder characterized by rare X-linked genetic immune deficiency with mutations in the Was gene, which is specifically expressed in hematopoietic cells. The spleen plays a major role in hematopoiesis and red blood cell clearance. However, to date, comprehensive analyses of the spleen in wild-type (WT) and WASp-deficient (WAS-KO) mice, especially at the transcriptome level, have not been reported. In this study, single-cell RNA sequencing (scRNA-seq) was adopted to identify various types of immune cells and investigate the mechanisms underlying immune deficiency. We identified 30 clusters and 10 major cell subtypes among 11,269 cells; these cell types included B cells, T cells, dendritic cells (DCs), natural killer (NK) cells, monocytes, macrophages, granulocytes, stem cells and erythrocytes. Moreover, we evaluated gene expression differences among cell subtypes, identified differentially expressed genes (DEGs), and performed enrichment analyses to identify the reasons for the dysfunction in these different cell populations in WAS. Furthermore, some key genes were identified based on a comparison of the DEGs in each cell type involved in specific and nonspecific immune responses, and further analysis showed that these key genes were previously undiscovered pathology-related genes in WAS-KO mice. In summary, we present a landscape of immune cells in the spleen of WAS-KO mice based on detailed data obtained at single-cell resolution. These unprecedented data revealed the transcriptional characteristics of specific and nonspecific immune cells, and the key genes were identified, laying a foundation for future studies of WAS, especially studies into novel and underexplored mechanisms that may improve gene therapies for WAS.

Leptin Receptor Gln223Arg Polymorphism of Human Spermatozoa Associated with Male Infertility in a Chinese Population.

Background: Leptin (LEP) is believed to play a crucial role in male reproduction, while the molecular mechanisms through which LEP affects the male reproductive system are unclear. LEP acts by binding to a leptin receptor (LEPR) which mediates its physiological action, but there are only limited studies on the function of LEPR in human sperm. Purpose: This study aimed to determine the Gln223Arg polymorphisms of the LEPR gene in human spermatozoa and evaluate their possible relationship with semen variables. Methods: The study was performed on Chinese men: 115 healthy subjects and 108 patients with primary and 98 with secondary infertility. Semen samples were obtained from all patients, and semen variables were analyzed. The genotypic and allelic frequencies of Gln223Arg polymorphism in spermatozoa were determined by PCR and restriction fragment length polymorphism (RFLP) analyses. Statistical analyses were performed using the chi-square test, the Kruskal-Wallis test, and the Mann-Whitney test. Results: There were no significant differences in genotypic or allelic frequency distributions of Gln223Arg polymorphism among men with primary infertility, secondary infertility, and controls. Similarly, semen volume and sperm concentration did not differ with the different genotypes in all groups of men. The percentages of motile sperm for AA + AG genotypes in men with primary infertility (31.98%) were significantly lower than those in secondary infertility, and control men with GG genotypes were 34.41% and 59.36%, respectively. At the same time, the percentages of normal morphology sperm for AA + AG genotypes in men with primary infertility (2.93%) were significantly lower than those in secondary infertility and control men with GG genotypes 3.71% and 6.54%, respectively. Conclusion: This study reveals a possible association between the Gln223Arg polymorphism of the LEPR gene in spermatozoa affecting spermatozoal membrane integrity and having a direct role in sperm motility.

Effects of organic zinc on production performance, meat quality, apparent nutrient digestibility and gut microbiota of broilers fed low-protein diets.

The high cost of feed and nitrogen pollution caused by high-protein diets have become major challenges restricting sustainable development in China's animal husbandry sector. Properly reducing protein levels and improving protein utilization in feed are effective approaches to solving this problem. To determine the optimal dose of methionine hydroxyl analogue chelated zinc (MHA-Zn) in broiler diets with a 1.5% reduction in crude protein (CP), a total of 216 1-day-old broilers were randomly assigned into 4 groups (each group consisted of 3 replications with 18 broilers per replicate), and growth and development indexes were assessed after 42 days. The broilers in control group were fed a basic diet, whereas those in the three test groups were fed diets with a 1.5% reduction in CP. The results showed no significant difference in the edible parts of broilers between low-protein (LP) diet group (90 mg/kg MHA-Zn) and normal diet group (p > 0.05), and adding 90 mg/kg MHA-Zn to LP diet significantly improved ileum morphology and apparent total tract digestibility (ATTD) of nutrient (p < 0.01; p < 0.05). A 16S rRNA sequencing analysis indicated that supplementing the LP diet with 90 mg/kg MHA-Zn was adequate for production performance of broilers and promoted beneficial bacteria in the cecum (Lactobacillus, Butyricoccus, Oscillospira, etc.) (p < 0.01). In summary, adding an optimal dose of organic zinc (90 mg/kg MHA-Zn) in low protein diets led to enhanced production performance of broilers and optimized cecum microbiota. Additionally, the reduction of crude protein consumption in broiler production proved to be a cost-effective measure, while also mitigated nitrogen pollutant emissions in the environment.

Association of vitamin D in individuals with periodontitis: an updated systematic review and meta-analysis.

BACKGROUND: There are differences in vitamin D levels between periodontitis and healthy individuals, but the effect of vitamin D on periodontitis is controversial. The purpose of this Meta-analysis is twofold: (1) compare vitamin D levels in individuals with or without periodontitis; (2) assess the effects of vitamin D supplementation during scaling and root planing (SRP) on periodontal clinical parameters in individuals with periodontitis. METHODS: A systematic search was conducted in five databases (PubMed, Web of Science, MEDLINE, EMBASE, and Cochrane library), published from the database inception to 12 September 2022. The Cochrane Collaboration Risk of bias (ROB) assessment tool, the risk of bias in non-randomized studies of intervention (ROBINS-I) tool, the Newcastle-Ottawa Quality Assessment Scale (NOS), and Agency for Healthcare Quality and Research (AHRQ) were used to evaluate randomized controlled trial (RCT), non-RCT, case-control study, and cross-sectional study, respectively. Statistical analysis was performed using RevMan 5.3 and Stata 14.0 software, with weighted mean difference (WMD), standardized mean difference (SMD) and 95% confidence intervals (CI) as the effect measures, and heterogeneity was tested by subgroup analysis, sensitivity analysis, Meta-regression. RESULTS: A total of 16 articles were included. The results of Meta-analysis showed that periodontitis was associated with lower serum vitamin D levels compared to normal population (SMD = -0.88, 95%CI -1.75 ~ -0.01, P = 0.048), while there was no significant difference in serum or saliva 25(OH)D levels between periodontitis and normal population. Additionally, the Meta-analysis showed that SRP + vitamin D and SRP alone had a statistically significant effect on serum vitamin D levels in individuals with periodontitis (SMD = 23.67, 95%CI 8.05 ~ 32.29, P = 0.003; SMD = 1.57, 95%CI 1.08 ~ 2.06, P < 0.01). And SRP + vitamin D could significantly reduce clinical attachment level compared to SRP alone (WMD = -0.13, 95%CI -0.19 ~ -0.06, P < 0.01), but had no meaningful effect on probing depth, gingival index, bleeding index, respectively. CONCLUSION: The evidence from this Meta-analysis suggests that the serum vitamin D concentration of individuals with periodontitis is lower than that of normal people, and SRP along with vitamin D supplementation has been shown to play a significant role in improving periodontal clinical parameters. Therefore, vitamin D supplementation as an adjuvant to nonsurgical periodontal therapy has a positive impact on the prevention and treatment of periodontal disease in clinical practice.

Transcriptomic insights into the role of the spleen in a mouse model of Wiskott­Aldrich syndrome.

Wiskott-Aldrich syndrome (WAS) is a rare X-linked primary immunodeficiency characterized by microthrombocytopenia, eczema, recurrent infection and increased incidence of autoimmune disorders and malignancy. WAS is caused by mutations in the was gene, which is expressed exclusively in hematopoietic cells; the spleen serves an important role in hematopoiesis and red blood cell clearance. However, to the best of our knowledge, detailed comparative analysis of the spleen between WASp-knockout (WAS-KO) and wild-type (WT) mice, particularly at the transcriptomic level, have not been reported. The present study investigated the differences in the transcriptomes of spleen tissue of 10-week-old WAS-KO mice. Comparison of the gene expression profiles of WAS-KO and WT mice revealed 1,964 differentially expressed genes (DEGs). Among these genes, 996 DEGs were upregulated and 968 were downregulated in WAS-KO mice. To determine the functions of DEGs, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed for significantly upregulated and downregulated DEGs. The results showed that the levels of cell senescence and apoptosis-associated genes were increased, antigen processing and presentation mechanisms involved in the immune response were damaged and signal transduction processes were impaired in the spleen of WAS-KO mice. Thus, was gene deletion may lead to anemia and hemolysis-associated disease, primarily due to increased osmotic fragility of red blood cells, low hemoglobin and increased bilirubin levels and serum ferritin. These results indicated that senescence and apoptosis of blood cells also play an important role in the occurrence of WAS. Therefore, the present findings provide a theoretical basis for further study to improve the treatment of WAS.

There is a Good Consistency Between Reflux Symptom Score-12 and Reflux Symptom Index in Chinese Population.

OBJECTIVE: To investigate the consistency between the Reflux Symptom Score-12 (RSS-12) and Reflux Symptom Index (RSI) in Chinese people. METHODS: Patients with symptoms of LPR from the outpatient otorhinolaryngology-head and neck surgery clinic were included. All included patients completed the RSS-12 and RSI. The patient with RSS-12>11 or RSI>13 suggested possible LPR. For the patients with RSI >13 or RSS-12>11, they were treated using diet recommendations and were prescribed a twice-daily pantoprazole for 12 weeks. The consistency between the RSS-12 and RSI was compared with the weighted Cohen's kappa statistic. RESULTS: A total of 258 patients were included. The mean scores for RSS-12 and RSI were 13.21±17.31 and 12.86±6.15, respectively. The positive rate of LPR was 17.44% based on the RSI, and 24.42% based on the RSS-12. The kappa value between the RSS-12 and RSI was 0.736 (P < 0.001). Following 12 weeks of treatment, there was a significant reduction in both RSI and RSS-12. Based on the RSI, 73% of patients had a good treatment response, whereas according to the RSS-12, 85% of patients had a good treatment response. CONCLUSION: There is a good consistency between RSS-12 and RSI, meaning that the RSS-12 is a feasible LPR initial screening tool. The RSS-12 provides a more comprehensive evaluation of reflux symptoms and treatment effect than RSI in patients with LPR.

Prevalence and treatment of venous thromboembolism in patients with solid tumors.

Cancer-associated venous thromboembolism (VTE) has exhibited a rising incidence rate. Research focusing on cancer-associated VTE and current anticoagulation therapy strategies is limited. The present study aimed to investigate the prevalence, characteristics and anticoagulation therapy strategies of cancer-associated VTE. The study was performed on patients with major solid tumors who were admitted to The First Affiliated Hospital of Guangxi Medical University (Nanning, China) between January 2020 and December 2020. The medical records of the patients' demographic characteristics, disease and treatment were extracted from the medical record data system and reviewed. The prevalence of cancer-associated VTE was calculated, followed by statistical analysis. Patients who received anticoagulation therapy for cancer-associated VTE were followed up for 1 year. The characteristics and efficacy of anticoagulation therapy strategies were compared and analyzed. A total of 4,926 patients with major solid tumors (mean age, 55.86±11.97 years) were included in the analysis, of which 117 (2.4%; 117/4,926) were diagnosed with cancer-associated VTE. Patients with pancreatic cancer exhibited the highest prevalence of VTE (10.2%; 5/49), followed by patients with ovarian cancer (5.8%; 9/156) and lung cancer (3.3; 73/2,237). Multivariate analysis identified hypertension comorbidity [odds ratio (OR), 1.661; 95% CI, 1.031-2.674; P=0.037)] and cancer stage (OR, 1.266; 95% CI, 1.079-1.486; P=0.004) as independent risk factors for cancer-associated VTE. Deep vein thrombosis (DVT) of the lower extremity accounted for 62.0%; 62/100) of all DVTs. Moreover, pulmonary embolism (PE) with lower extremity DVT accounted for 53.5% (23/43) of all PE cases. The majority of cancer-associated VTE cases (63.2%; 74/117) developed 30 days before or after a cancer diagnosis. In addition, cancer-associated VTE was dominated by symptomatic VTE (59.8%; 70/117). Only 74.4% (87/117) of patients with VTE received anticoagulant treatment, with a median duration of 79 days. The most common anticoagulant treatment strategies were heparin during hospitalization and direct oral anticoagulants (rivaroxaban) after discharge. The anticoagulants associated with bleeding events were rivaroxaban (4.2%; 3/72) and enoxaparin (1.9%; 1/54). In total, 62.1% (36/58) of the patients received anticoagulant treatment for <90 days. In conclusion, the results indicated that the prevalence of cancer-associated VTE is common and exhibits numerous characteristics. Rivaroxaban has been widely used in cancer-associated VTE treatment. However, compliance with long-term anticoagulant treatment is not adequate at present, while the efficacy and safety of rivaroxaban must be evaluated to improve long-term medication monitoring and follow-up among patients with cancer-associated VTE.

Leptin Levels in Serum or Semen and Its Association with Male Infertility: A Meta-Analysis with 1138 Cases.

Background: Leptin has an association with male infertility. However, only sporadic studies inconsistently reported the results. Aim and Objective. In this study, we aimed to perform a meta-analysis to investigate the relationship between leptin and male infertility. Methods: This study was performed based on published articles related to leptin and infertile males. PubMed, Web of Science, Google Scholar, Ovid + Cochrane Central Register of Controlled Trials, Wiley Online Library, Chinese CNKI, Chinese Chong Qing VIP, Chinese Wan Fang, and China Biology Medicine databases were searched to identify all relevant studies. All eligible works of literature were analyzed by the "meta" or "metan" command in STATA version 12.0 software. The standardized mean difference (SMD) of leptin concentration in serum or semen and 95% confidence intervals (CIs) were estimated for all studies. The heterogeneity was described with I2. The sources of heterogeneity were explored via metaregression, and stratified analyses, sensitivity analyses, and publication bias were performed. Results: Nineteen studies were included in the current meta-analysis, involving 1138 cases of infertile men and 756 controls. The SMD of leptin concentration in serum was 2.002 (95% CI: 1.086, 2.918), Z-test (z) z = 4.29; p < 0.001, and I2 was 97.3%, p < 0.001. The SMD of leptin concentration in semen was 3.274 (95% CI: 2.137, 4.411), z = 5.64; p < 0.001, and I2 was 98.2%, p < 0.001. Notably, serum follicle-stimulating hormone (FSH) was slightly higher in infertile men (SMD = 3.695, z = 2.33, p = 0.020, I2 = 98.8%, p < 0.001). Other hormones, such as luteinizing hormone (LH) and testosterone, were also slightly higher, but the results were not statistically significant. In addition, sperm count (SMD = -4.533, 95% CI: -6.565, -2.501) and sperm motility (SMD = -7.894, 95% CI: -10.616, -5.172) inversely correlated with leptin levels in infertile males. Sperm abnormal forms did not show a statistically significant SMD of -0.076 (95% CI: -3.410, 3.258). Conclusion: Leptin plays a potential role in association with male infertility. This study may effectively reveal the relationship between leptin together with other hormones and its association with male infertility. These results may also provide opinions on precautionary measures.

Effect of season on slaughter performance, meat quality, muscle amino acid and fatty acid composition, and metabolism of pheasants (Phasianus colchicus).

This study aimed to investigate the effect of summer and winter on slaughter performance, muscle quality, flavor-related substance content, and gene expression levels related to the fat metabolism of pheasants. One-hundred 1-day-old pheasants were fed for 5 months starting in March and July and then, respectively, slaughtered in summer (August) and winter (December). The results revealed that compared with summer, winter not only increased pheasant live weight, dressed percentage, full-eviscerated yield, and muscle yield (p < 0.05) but also enhanced the activities of SOD and CAT in serum (p < 0.05). Winter significantly increased meat color, the contents of inosinic acid, and flavor amino acid in muscle. Amino acid contents in leg muscles of pheasants in winter were significantly higher than in summer except for histidine (p < 0.05). Winter increased the contents of muscle mono-unsaturated fatty acid, reducing saturated fatty acid. Summer improved fat synthesis in liver, promoted the deposition of triglycerides and cholesterol, and reduced the expression levels of fat metabolism-related genes in muscle, while winter increased the expression levels of genes related to muscle fat metabolism to provide energy for body and affect muscle fatty acid profile. Overall, pheasants fed in winter had better sensory quality and flavor than summer.

Long non-coding RNA small nucleolar RNA host gene 1 alleviates the progression of recurrent spontaneous abortion via the microRNA-183-5p/ZEB2 axis.

Long non-coding RNAs (lncRNAs) have been elucidated to play vital roles in the phenotype of trophoblast cells. Nevertheless, the effect of SNHG1 has not been investigated on trophoblast cells in recurrent spontaneous abortion (RSA). We aim to investigate the effect of SNHG1 on the phenotype of trophoblast cells during RSA. The RSA mice were established by mating female CBA/J mice with male DBA/2 mice. Microarray analysis was applied in RSA mice, and SNHG1 was identified as a significantly downregulated lncRNA. SNHG1 improved pregnancy outcome and reduced embryo resorption in RSA mice. Trophoblast cell proliferation, apoptosis, migration, and invasion were investigated by CCK8, EdU, TUNEL, wound healing, and Transwell assays. SNHG1 promoted proliferation, migration, and invasion of trophoblast cells, and reduced apoptosis. Mechanistically, SNHG1 bound to miR-183-5p in trophoblast cells. Moreover, miR-183-5p directly targeted ZEB2. Rescue experiment showed that ZEB2 silencing reversed the ameliorative effect of SNHG1 on pregnancy outcome and the promotion of trophoblast activity in RSA mice by impaired the Wnt/ß-catenin pathway. In conclusion, we found that SNHG1 plays a critical role in the progression of RSA via miR-183-5p/ZEB2 and Wnt/ß-catenin signaling. It has potential to be a therapeutic marker of RSA.

Microwave ablation versus laparoscopic resection as first-line therapy for solitary 3-5-cm HCC.

BACKGROUND AND AIMS: The study objective was to compare the effectiveness of microwave ablation (MWA) and laparoscopic liver resection (LLR) on solitary 3-5-cm HCC over time. APPROACH AND RESULTS: From 2008 to 2019, 1289 patients from 12 hospitals were enrolled in this retrospective study. Diagnosis of all lesions were based on histopathology. Propensity score matching was used to balance all baseline variables between the two groups in 2008-2019 (n = 335 in each group) and 2014-2019 (n = 257 in each group) cohorts, respectively. For cohort 2008-2019, during a median follow-up of 35.8 months, there were no differences in overall survival (OS) between MWA and LLR (HR: 0.88, 95% CI 0.65-1.19, p = 0.420), and MWA was inferior to LLR regarding disease-free survival (DFS) (HR 1.36, 95% CI 1.05-1.75, p = 0.017). For cohort 2014-2019, there was comparable OS (HR 0.85, 95% CI 0.56-1.30, p = 0.460) and approached statistical significance for DFS (HR 1.33, 95% CI 0.98-1.82, p = 0.071) between MWA and LLR. Subgroup analyses showed comparable OS in 3.1-4.0-cm HCCs (HR 0.88, 95% CI 0.53-1.47, p = 0.630) and 4.1-5.0-cm HCCs (HR 0.77, 95% CI 0.37-1.60, p = 0.483) between two modalities. For both cohorts, MWA shared comparable major complications (both p > 0.05), shorter hospitalization, and lower cost to LLR (all p < 0.001). CONCLUSIONS: MWA might be a first-line alternative to LLR for solitary 3-5-cm HCC in selected patients with technical advances, especially for patients unsuitable for LLR.

Evaluation of a new frequency-volume chart for children with primary monosymptomatic nocturnal enuresis: a prospective, comparative study.

INTRODUCTION: To improve compliance with voiding diaries in children with primary monosymptomatic nocturnal enuresis (PMNE), a new modified 3-day weekend frequency-volume chart (FVC) was designed, and the compliance and validity of this modified FVC was evaluated by comparing with the International Children's Continence Society (ICCS) recommended voiding diary. METHODS: A total of 1200 patients with PMNE were enrolled in the study from 13 centers in China and were randomly assigned to record this modified FVC or the ICCS-recommended voiding diary. The primary outcome measure was the compliance, assessed by comparing the completing index and the quality score of diaries between two groups. The secondary outcome measure was the validity, evaluated by comparing the constituent of subtypes, micturition parameters and response rate to desmopressin. RESULTS: Among the 1200 participants enrolled in the study, 447 patients completed the ICCS-recommended voiding diary and 469 completed the modified diary. The diurnal completing index and the quality score of the modified FVC group were better than those of the ICCS group. In addition, there was no significant difference between these two groups in the subtype classification, or in the response rate to desmopressin. CONCLUSIONS: The modified FVC could be applied to obtain the voiding characteristics of children with PMNE as the ICCS-recommended voiding diary does and offers a reasonable and better choice for children with PMNE from the unselected population in the future.

Prognostic factors of patients after liver cancer surgery: Based on Surveillance, Epidemiology, and End Results database.

ABSTRACT: This study aimed to investigate the prognostic factors of patients after liver cancer surgery and evaluate the predictive power of nomogram. Liver cancer patients with the history of surgery in the Surveillance, Epidemiology, and End Results database between 2000 and 2016 were preliminary retrieved. Patients were divided into the survival group (n = 2120, survival ≥5 years) and the death group (n = 2615, survival < 5 years). Single-factor and multi-factor Cox regression were used for analyzing the risk factors of death in patients with liver cancer after surgery. Compared with single patients, married status was the protective factor for death in patients undergoing liver cancer surgery (HR = 0.757, 95%CI: 0.685-0.837, P < .001); the risk of death in Afro-Americans (HR = 1.300, 95%CI: 1.166-1.449, P < .001) was higher than that in Caucasians, while the occurrence of death in Asians (HR = 0.821, 95%CI: 0.1754-0.895, P < .0012) was lower; female patients had a lower incidence of death (HR = 0.875, 95%CI: 0.809-0.947, P < .001); grade II (HR = 1.167, 95%CI: 1.080-1.262, P < .001), III (HR = 1.580, 95%CI: 1.433-1.744, P < .001), and IV (HR = 1.419, 95%CI: 1.145-1.758, P = 0.001) were the risk factors for death in patients with liver cancer. The prognostic factors of liver cancer patients after surgery include the marital status, race, gender, age, grade of cancer and tumor size. The nomogram with good predictive ability can provide the prediction of 5-year survival for clinical development.

Preoperative Predictors of Lymph Node Metastasis in Colon Cancer.

BACKGROUND: Lymph node metastasis (LNM) is a well-established prognostic factor for colon cancer. Preoperative LNM evaluation is relevant for planning colon cancer treatment. The aim of this study was to construct and evaluate a nomogram for predicting LNM in primary colon cancer according to pathological features. PATIENTS AND METHODS: Six-hundred patients with clinicopathologically confirmed colon cancer (481 cases in the training set and 119 cases in the validation set) were enrolled in the Affiliated Cancer Hospital of Guangxi Medical University from January 2010 to December 2019. The expression of molecular markers (p53 and ß-catenin) was determined by immunohistochemistry. Multivariate logistic regression was used to screen out independent risk factors, and a nomogram was established. The accuracy and discriminability of the nomogram were evaluated by consistency index and calibration curve. RESULTS: Univariate logistic analysis revealed that LNM in colon cancer is significantly correlated (P <0.05) with tumor size, grading, stage, preoperative carcinoembryonic antigen (CEA) level, and peripheral nerve infiltration (PNI). Multivariate logistic regression analysis confirmed that CEA, grading, and PNI were independent prognostic factors of LNM (P <0.05). The nomogram for predicting LNM risk showed acceptable consistency and calibration capability in the training and validation sets. CONCLUSIONS: Preoperative CEA level, grading, and PNI were independent risk factor for LNM. Based on the present parameters, the constructed prediction model of LNM has potential application value.

Extracellular vesicles in Inter-Kingdom communication in gastrointestinal cancer.

The production and secretion of extracellular vesicles (EVs) are common features of cells (including various normal cells, neoplastic cell lines as well as bacteria) that span all domains of life. Tumor-derived exosomes are enriched with kinds of tumorigenesis mediators which are derived from the cytoplasm of cancer cells and fully reflect the tumor conditions. Indeed, the major topics and challenges on current oncological research are the identification of tumorigenic and metastatic molecules in tumor-cell-derived exosomes as well as elucidating the pathways that guarantee these components to be included in exosomes. The bacterial EVs have also been implicated in the pathogenesis of gastrointestinal (GI) tumors and chronic inflammatory diseases; however, the possible function of outer membrane vesicles (OMVs) in tumorigenesis remains largely underestimated. We suggest that EVs from both eukaryotic cells and different microbes in GI tract act as regulators of intracellular and cross-species communication, thus particularly facilitate tumor cell survival and multi-drug resistance. Therefore, our review introduces comprehensive knowledge on the promising role of EVs (mainly exosomes and OMVs) production of GI cancer development and gut microbiome, as well as its roles in developing novel therapeutic strategies.

PbEIL1 acts upstream of PbCysp1 to regulate ovule senescence in seedless pear.

Numerous environmental and endogenous signals control the highly orchestrated and intricate process of plant senescence. Ethylene, a well-known inducer of senescence, has long been considered a key endogenous regulator of leaf and flower senescence, but the molecular mechanism of ethylene-induced ovule senescence has not yet been elucidated. In this study, we found that blockage of fertilization caused ovule abortion in the pear cultivar '1913'. According to transcriptome and phytohormone content data, ethylene biosynthesis was activated by pollination. At the same time, ethylene overaccumulated in ovules, where cells were sensitive to ethylene signals in the absence of fertilization. We identified a transcription factor in the ethylene signal response, ethylene-insensitive 3-like (EIL1), as a likely participant in ovule senescence. Overexpression of PbEIL1 in tomato caused precocious onset of ovule senescence. We further found that EIL1 could directly bind to the promoter of the SENESCENCE-ASSOCIATED CYSTEINE PROTEINASE 1 (PbCysp1) gene and act upstream of senescence. Yeast one-hybrid and dual-luciferase assays revealed the interaction of the transcription factor and the promoter DNA sequence and demonstrated that PbEIL1 enhanced the action of PbCysp1. Collectively, our results provide new insights into how ethylene promotes the progression of unfertilized ovule senescence.

Correction: Zheng, L., et al. PBN11-8, a Cytotoxic Polypeptide Purified from Marine Bacillus, Suppresses Invasion and Migration of Human Hepatocellular Carcinoma Cells by Targeting Focal Adhesion Kinase Pathways. Polymers 2018, 10, 1043.

The authors wish to make a change to the published paper [...].