Renal protective effect and clinical analysis of vitamin B6 in patients with sepsis.

OBJECTIVE: To investigate the protective effect and possible mechanisms of vitamin B6 against renal injury in patients with sepsis. METHODS: A total of 128 patients with sepsis who met the entry criteria in multiple centres were randomly divided into experimental (intravenous vitamin B6 therapy) and control (intravenous 0.9% sodium chloride therapy) groups based on usual care. Clinical data, the inflammatory response indicators interleukin 6 (IL-6), interleukin 8 (IL-8), tumour necrosis factor (TNF-α) and endothelin-1 (ET-1), the oxidative stress response indicators superoxide dismutase, glutathione and malondialdehyde, and renal function (assessed by blood urea nitrogen [BUN], serum creatinine [SCr] and renal resistance index [RRI] monitored by ultrasound) were compared between the two groups. RESULTS: After 7 d of treatment, the IL-6, IL-8, TNF-α and ET-1 levels in the experimental group were significantly lower than those in the control group, the oxidative stress response indicators were significantly improved in the experimental group and the BUN, SCr and RRI values in the experimental group were significantly lower than those in the control group (p < 0.05). There was no statistical difference between the two groups in the rate of renal replacement therapy and 28 d mortality (p > 0.05). However, the ICU length of stay and the total hospitalisation expenses in the experimental group were significantly lower than those in the control group (p < 0.05). CONCLUSION: The administration of vitamin B6 in the treatment of patients with sepsis attenuates renal injury, and the mechanism may be related to pyridoxine decreasing the levels of inflammatory mediators and their regulation by redox stress.Clinical trial registration: ClinicalTrials.gov Identifier: NCT06008223.

COVID-19 vaccination affects short-term anti-coagulation levels in warfarin treatment.

Vaccines against SARS-CoV-2 have been recommended across the world, yet no study has investigated whether COVID-19 vaccination influences short-term warfarin anti-coagulation levels. Patients on stable warfarin treatment who received anti-SARS-CoV-2 vaccination were prospectively enrolled and followed up for three months. INR values less than 10 days before vaccination (baseline), 3-5 days (short-term) and 6-14 days (medium-term) after vaccination were recorded as INR0, INR1, and INR2, respectively. The variations of INR values within individuals were compared, and the linear mixed effect model was used to evaluate the variations of INR values at different time points. Logistic regression analysis was performed to determine covariates related to INR variations after COVID-19 vaccination. Vaccination safety was also monitored. There was a significant difference in INR values between INR0 and INR1 (2.15 vs. 2.26, p = 0.003), yet no marked difference was found between INR0 and INR2. The linear mixed effect model also demonstrated that INR variation was significant in short-term but not in medium-term or long-term period after vaccination. Logistic regression analysis showed that no investigated covariates, including age, vaccine dose, genetic polymorphisms of VKORC1 and CYP2C9 etc., were associated with short-term INR variations. Two patients (2.11%) reported gingival hemorrhage in the short-term due to increased INR values. The overall safety of COVID-19 vaccines for patients on warfarin was satisfying. COVID-19 vaccines may significantly influence warfarin anticoagulation levels 3-5 days after vaccination. We recommend patients on warfarin to perform at least one INR monitoring within the first week after COVID-19 vaccination.

Epigenetic modification: A novel insight into diabetic wound healing.

Wound healing is an intricate and fine regulatory process. In diabetic patients, advanced glycation end products (AGEs), excessive reactive oxygen species (ROS), biofilm formation, persistent inflammation, and angiogenesis regression contribute to delayed wound healing. Epigenetics, the fast-moving science in the 21st century, has been up to date and associated with diabetic wound repair. In this review, we go over the functions of epigenetics in diabetic wound repair in retrospect, covering transcriptional and posttranscriptional regulation. Among these, we found that histone modification is widely involved in inflammation and angiogenesis by affecting macrophages and endothelial cells. DNA methylation is involved in factors regulation in wound repair but also affects the differentiation phenotype of cells in hyperglycemia. In addition, noncodingRNA regulation and RNA modification in diabetic wound repair were also generalized. The future prospects for epigenetic applications are discussed in the end. In conclusion, the study suggests that epigenetics is an integral regulatory mechanism in diabetic wound healing.

Directed Evolution of Escherichia coli Nissle 1917 to Utilize Allulose as Sole Carbon Source.

Sugar substitutes are popular due to their akin taste and low calories. However, excessive use of aspartame and erythritol can have varying effects. While D-allulose is presently deemed a secure alternative to sugar, its excessive consumption is not devoid of cellular stress implications. In this study, the evolution of Escherichia coli Nissle 1917 (EcN) is directed to utilize allulose as sole carbon source through a combination of adaptive laboratory evolution (ALE) and fluorescence-activated droplet sorting (FADS) techniques. Employing whole genome sequencing (WGS) and clustered regularly interspaced short palindromic repeats interference (CRISPRi) in conjunction with compensatory expression displayed those genetic mutations in sugar and amino acid metabolic pathways, including glnP, glpF, gmpA, nagE, pgmB, ybaN, etc., increased allulose assimilation. Enzyme-substrate dynamics simulations and deep learning predict enhanced substrate specificity and catalytic efficiency in nagE A247E and pgmB G12R mutants. The findings evince that these mutations hold considerable promise in enhancing allulose uptake and facilitating its conversion into glycolysis, thus signifying the emergence of a novel metabolic pathway for allulose utilization. These revelations bear immense potential for the sustainable utilization of D-allulose in promoting health and well-being.

Cordythiazole A, the first member of thiazole alkaloids from Chinese cordyceps, with α-glucosidase inhibitory activity.

Chinese cordyceps, also known as Dong-Chong-Xia-Cao, is widely recognized as a famous precious tonic herb, and used as traditional Chinese medicine for centuries. It is mainly used for regulating the immune system and improving functions of the lung and kidney, with anti-tumor, anti-inflammatory, and anti-diabetic activities. Due to its rarity and preciousness, a few chemical components are isolated and identified. Moreover, most of them are common chemical components and widely distributed in other natural resources, such as nucleosides, sterols, fatty acids, sugar alcohols, and peptides. Therefore, a large number of active substances of Chinese cordyceps is still unclear. During our search for chemical constituents of Chinese cordyceps, a new thiazole alkaloid, cordythiazole A (1), was isolated and identified. Its structure was elucidated by comprehensive spectroscopic analysis and single-crystal X-ray diffraction analysis. This is the first report of the presence of thiazole alkaloid in Chinese cordyceps, which adds a new class of metabolite of Chinese cordyceps. Furthermore, a putative biosynthesis pathway of cordythiazole A was proposed based on possible biogenic precursor, genes, and literatures. In addition, it showed α-glucosidase inhibitory activity with potency close to that of acarbose. The discovery of cordythiazole A with α-glucosidase inhibitory activity adds a new class of potential anti-diabetes ingredient in Chinese cordyceps.

[Effect of Sparganii Rhizoma-Curcumae Rhizoma-medicated serum on proliferation, apoptosis, and migration of human ectopic endometrial stromal cells: based on JAK2/STAT3 signaling pathway].

Based on the Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3) signaling pathway, this study investigated the effect of medicated serum of Sparganii Rhizoma(SR) and Curcumae Rhizoma(CR) on the proliferation, apoptosis, migration, and secretion of inflammatory factors of ectopic endometrial stromal cells(ESCs). Specifically, human ESCs were primary-cultured. The effect of different concentration(5%, 10%, 20%) of SR-, CR-, and SR-CR combination-medicated serum, and AG490 solution(50 µmol·L~(-1)) on the proliferation of ESCs was detected by methyl thiazolyl tetrazolium(MTT) assay, and the optimal dose was selected accordingly for further experiment. The cells were classified into normal serum(NS) group, SR group(10%), CR group(10%), combination(CM) group(10%), and AG490 group. The apoptosis level of ESCs was detected by flow cytometry, and the migration ability was examined by wound healing assay. The secretion of interleukin(IL)-1ß, IL-6, and tumor necrosis factor(TNF)-α was determined by enzyme-linked immunosorbent assay(ELISA). The protein levels of cysteinyl aspartate specific protei-nase-3(caspase-3), B-cell lymphoma(Bcl-2), and Bcl-2-associated X protein(Bax) and the levels of phosphorylated(p)-JAK2 and p-STAT3 were detected by Western blot. The results showed that the viability of ESCs cells was lowered in the administration groups compared with the blank serum group(P<0.01), especially the 10% drug-medicated serum, which was selected for further experiment. The 10% SR-medicated serum, 10% CR-medicated serum, and 10% CM-medicated serum could increase the apoptosis rate(P<0.01), up-regulate the protein expression of caspase-3 and Bax in cells(P<0.05 or P<0.01), down-regulate the expression of Bcl-2(P<0.01), decrease the cell migration rate(P<0.05 or P<0.01), and reduce the secretion levels of IL-1ß, IL-6, and TNF-α(P<0.05 or P<0.01), and levels of p-JAK2 and p-STAT3(P<0.05 or P<0.01). Compared with the SR and CR groups, CM group showed low cell viability(P<0.01), high protein expression of caspase-3 and Bax(P<0.05 or P<0.01), and low protein expression of Bcl-2 and p-JAK2(P<0.05). After incubation with CM, the apoptosis rate was higher(P<0.05) and the migration rate was lower(P<0.01) than that of the CR group. The p-STAT3 protein level of CM group was lower than that of the RS group(P<0.05). The mechanism of SR, CR, and the combination underlying the improvement of endometriosis may be that they blocked JAK2/STAT3 signaling pathway, inhibited ESC proliferation, promoted apoptosis, weakened cell migration, and reduced the secretion of inflammatory factors. The effect of the combination was better than that of RS alone and CR alone.

Knockdown of the long non­coding RNA MALAT1 ameliorates TNF­α­mediated endothelial cell pyroptosis via the miR­30c­5p/Cx43 axis.

Long noncoding RNAs (lncRNAs) are related to the development of atherosclerosis (AS). However, the role of lncRNA metastasis associated lung adenocarcinoma transcript 1 (MALAT1) in tumor necrosis factor­α (TNF­α)­induced rat aortic endothelial cell (RAOEC) pyroptosis, as well as the underlying mechanisms, remain unclear. RAOEC morphology was assessed using an inverted microscope. The mRNA and/or protein expression levels of MALAT1, microRNA(miR)­30c­5p and connexin 43 (Cx43) were assessed using reverse transcription­quantitative PCR (RT­qPCR) and/or western blotting, respectively. The relationships among these molecules were validated by dual­luciferase reporter assays. Biological functions, such as LDH release, pyroptosis­associated protein levels and the proportion of PI­positive cells, were evaluated using a LDH assay kit, western blotting and Hoechst 33342/PI staining, respectively. The present study demonstrated that compared with the control group, the mRNA expression levels of MALAT1 and protein expression levels of Cx43 were significantly up­regulated, whereas miR­30c­5p mRNA expressions levels were significantly decreased in TNF­α­treated RAOEC pyroptosis. Knockdown of MALAT1 or Cx43 significantly attenuated the increase in LDH release, pyroptosis­associated protein expression and PI­positive cell numbers among RAOEC treated using TNF­α, whereas an miR­30c­5p mimic exerted the opposite effect. Furthermore, miR­30c­5p was demonstrated to be a negative regulator of MALAT1 and could also target Cx43. Finally, co­transfection with siMALAT1 and miR­30c­5p inhibitor could attenuate the protective effect of MALAT1 knockdown against TNF­α­mediated RAOEC pyroptosis by upregulation of Cx43 expression. In conclusion, MALAT1 might serve an important role in TNF­α­mediated RAOEC pyroptosis by regulating the miR­30c­5p/Cx43 axis, which would provide a potential novel diagnostic and therapeutic target for AS.

Circular RNA hsa_circ_0002938 (circCRIM1) promotes the progression of esophageal squamous cell carcinoma by upregulating transcription factor 12.

Growing evidence has indicated that circular RNAs (circRNAs) play crucial roles in the tumorigenesis and progression of diverse malignancies. However, the majority of circRNAs involved in esophageal squamous cell carcinoma (ESCC) remain undefined and the exact functions and underlying mechanisms of circRNAs in ESCC still need further exploration. In this study, we identified a novel onco-circRNA hsa_circ_0002938, derived from the exons of cysteine-rich transmembrane BMP regulator 1 (CRIM1) pre-mRNA, referred to as circCRIM1. We found that the expression of circCRIM1 was higher in ESCC tissues, compared to para-carcinoma tissues. Increased expression of circCRIM1 was positively correlated with clinical parameters of ESCC patients including tumor-node-metastasis (TNM) stage, tumor invasion range, and lymph node metastasis. Functionally, the results from the experiments in vitro showed that the knockdown of circCRIM1 suppressed proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) in ESCC cells. By conducting bioinformatics algorithms analyses and microRNA (miRNA) rescue experiments, we found that circCRIM1 could act as a competing endogenous RNA (ceRNA) to sponge miR-342-3p in ESCC cells, and thereby upregulated the expression of transcription factor 12 (TCF12), a key regulator promoting the EMT process. Taken together, circCRIM1 facilitates the progression of ESCC by sponging miR-342-3p to regulate TCF12 and promote EMT, and the circCRIM1/miR-342-3p/TCF12 axis may be regarded as a potential predictive biomarker and therapeutic target for treating ESCC.

KASP genotyping and semi-quantitation of G275E mutation in the α6 subunit of Thrips palmi nAChR gene conferring spinetoram resistance.

BACKGROUND: Pesticide resistance is a long-standing and growing problem in the chemical control of invertebrate pests. Molecular diagnostic methods can facilitate pesticide resistance management by accurately and efficiently detecting resistant mutations and their frequency. In this study, the kompetitive allele specific PCR (KASP) approach, a technology for high-throughput single nucleotide polymorphism (SNP) genotyping, is validated as a useful method for characterizing genotypes at a pesticide-resistance locus for the first time. We focus on the spinetoram resistance mutation of G275E in the nicotinic acetylcholine receptor alpha 6 (nAChR α6) subunit gene of Thrips palmi. RESULTS: Of the 341 individuals of Thrips palmi tested, 98.24% were successfully genotyped, with 100% concordance with Sanger sequencing results. We then quantitatively mixed genomic DNA of known genotypes to establish 21 DNA mixtures with a resistant allele frequency ranging from 0 to 100% at steps of 5%. The linear discriminant analysis (LDA) showed that 75.8% of original grouped cases were correctly classified; six groups had no overlap in membership (resistant allele frequency: 0%, 5%, 10-75%, 80-85%, 90-95%, and 100%). When we chose 11 pooled samples with 10% steps for LDA, 84.4% of original grouped cases were correctly classified; seven groups had no overlap in membership (0%, 10%, 20-30%, 40-70%, 80%, 90%, 100%). The results indicated that KASP applied to pooled samples may provide a semi-quantitative estimate of resistance. CONCLUSIONS: Our study points to the suitability of KASP for high-throughput genotyping of genotypes affecting pesticide resistance and semi-quantitative assessments of resistance allele frequencies in populations. © 2023 Society of Chemical Industry.

Comparison of involved-field intensity-modulated radiotherapy combined with S-1 vs radiotherapy alone for elderly patients with esophageal cancer.

BACKGROUND: It is estimated that about 30% of esophageal cancer (EC) patients are over 70 years old. Therefore, there is less evidence on the diagnosis and management of elderly EC patients. It is important to explore how elderly EC patients benefit from radical radiochemotherapy regimens, including the target area of radiotherapy (RT), radiation dose and fraction, and choice of chemotherapy drugs. AIM: To compare the efficacy of involved-field intensity-modulated RT (IF-IMRT) combined with S-1 vs RT alone in the treatment of elderly EC patients in terms of safety, short-term response, and survival. METHODS: Thirty-four EC patients aged > 70 years were prospectively enrolled between December 2017 and December 2019. Based on the random number table, they were divided into an IF-IMRT + S-1 group and an IF-IMRT alone group, with 17 patients in each group. All patients were treated with IF-IMRT at a dose of 50.4-56 Gy in 28-30 fractions (1.8-2 Gy/fraction, 5 fractions/wk). Oral S-1 was administered concomitantly in the IF-IMRT + S-1 group for 14 consecutive days, and a second cycle was started 7 d after drug withdrawal. After RT, 4 cycles of S-1 treatment were offered as the consolidation chemotherapy. The safety, short-term response, and survival were observed after the treatment. RESULTS: As of April 2022, these 34 patients had been followed up for 15.2-32.5 mo, with a median follow-up period of 24.5 mo. Complete efficacy indicators were obtained from all the patients. The objective response rate was 88.2% vs 76.5%, respectively, in the IF-IMRT + S-1 group and the RT alone group, where as the disease control rate was 100% vs 82.4%, respectively. The incidence of adverse events including grade 1-2 fatigue, granulocytopenia, thrombocytopenia, anemia, radiation esophagitis, radiation-induced skin injury, and radiation-induced lung injury was not significantly different between these two groups, so was the incidence of the grade 3 radiation esophagitis (0% vs 5.7%). The rate of progressive disease (PD) was 52.9% (n = 9) in the IF-IMRT + S-1 group and 64.7% (n = 11) in the RT alone group. The median progression-free survival (PFS) was 23.4 mo vs 16.3 mo, and the 2-year PFS rate was 42% vs 41.2%. The median overall survival (OS) was 27.0 mo vs 23.0 mo, and the 2-year OS rate was 58.8% vs 47.1%. Multivariate analysis showed that age was a significant prognostic factor (P = 0.0019); patients aged < 75 years had a significant survival advantage over patients aged ≥ 75 years. The locations of EC also affected the prognosis. In the IF-IMRT + S-1 group, the number of chemotherapy cycles was a significant prognostic factor (P = 0.0125), and the risk of PD was significantly lower in EC patients who had received 6 cycles of chemotherapy than those who had received 2-5 cycles of chemotherapy. CONCLUSION: Compared with IF-IMRT alone, IF-IMRT + S-1 shows the benefits of preventing PD and prolonging survival without increasing adverse reactions. Therefore, this concurrent radiochemotherapy deserves clinical application.

A [(M2)6L8] metal-organic polyhedron with high CO2 uptake and efficient chemical conversion of CO2 under ambient conditions.

A new metal-organic polyhedron with a high surface area of 407 m2 g-1, possessing high CO2 uptake, is reported, which is synthesized using 4-connected Cu2(CO2)4 paddle-wheel moieties and 3-connected semi-rigid tripodal carboxylates. This material possesses a high density of Cu(II) Lewis acidic sites and demonstrates excellent performance as a heterogeneous catalyst for the chemical fixation of CO2 into cyclic carbonates under ambient conditions.

JPHYD Inhibits miR-21-5p/Smad7-Mediated Epithelial-Mesenchymal Transition of Hepatocellular Carcinoma Cells.

Background: Studies have shown that Jianpi Huayu Decoction (JPHYD) can inhibit the growth of hepatocellular carcinoma cells, but the mechanism of its effect was not clear at present. Methods: We assessed the effect of JPHYD using liver cancer cells as in vitro cell model and xenograft tumor as in vivo model. CCK8, EdU, wound-healing, and transwell assays were performed to assess the cell growth, migration, and invasion of hepatocellular carcinoma (HCC) cell lines HepG2 and MHCC97H. Western blot assay was performed to observe the protein level of E-cadherin, Smad7, N-cadherin, Snail, Smad3, Vimentin, and Zeb1. qRT-PCR assay was used to observe the expression of miR-21-5p in clinical liver cancer tissue samples and in HepG2 and MHCC97H cells. Animal tumorigenesis experiments and in vivo imaging experiments were performed to assess the results of in vitro experiments. Results: We found that JPHYD could inhibit the proliferation, invasion, and migration of hepatocellular carcinoma cells and JPHYD decreased the level of N-cadherin, Snail, Vimentin, Smad3, and Zeb1 and increased E-cadherin and Smad7 proteins. The expression of miR-21-5p was increased while that protein of Smad7 was decreased in HCC tissues. The vivo experiments also showed that miR-21-5p could promote the migration of HCC cells. JPHYD decreased miR-21-5p expression. The same results have been found in animal studies. Conclusion: Our results indicated that JPHYD inhibited epithelial-mesenchymal transition by increasing Smad7 expression and inhibiting miR-21-5p. Therefore, blocking the occurrence and development of EMT may be a new mechanism of JPHYD's anti-liver cancer effect.

Reliability and Repeatability of the China-Japan Friendship Hospital Typing Classification for Nontraumatic Osteonecrosis of the Femoral Head.

BACKGROUND: The purpose of this study was to analyze the interobserver reliability and intraobserver repeatability of the China-Japan Friendship Hospital (CJFH) typing classification system for nontraumatic osteonecrosis of the femoral head (ONFH). METHODS: Image data of 50 hips were randomly selected in 289 patients (433 hips) with ONFH who underwent treatment in the China-Japan Friendship Hospital from 2012 to 2016. Bilateral hip plain radiography, magnetic resonance imaging (MRI), or computerized tomography (CT) were performed in all hips. The assessments were performed by 8 new residents independently, and the repeatability was assessed at 4-week intervals. Evaluation indicators included the size, location, and extent of necrotic lesions. Kappa values were used to determine the reliability and repeatability. RESULTS: According to the CJFH classification system, 2,800 evaluations were performed with an average interobserver Kappa value of 0.711, and 400 assessments were performed with an average intraobserver Kappa value of 0.748. Reliability analysis indicated a higher reliability and repeatability of this classification system. Critical factors affecting the consistency included the accurate selection of the median coronal plane and definitive tri-pillar division of the femoral head. CONCLUSION: The CJFH classification system is a simple and direct evaluation model for ONFH with substantial inter- and intraobserver reliability.

Construction of healthy enterprises in coal industry / 中国职业医学

@#Promoting the construction of healthy enterprises in the China's coal industry will help coal enterprises to fulfill their ， ， legal and social responsibilities contribute to the construction of healthy cities and protect the health of occupational ， ， individuals from various aspects. In recent years the patriotic health campaign the health promotion project of industrial and ， ， ， mining enterprises the construction of standardized management system of coal mine safety the construction of green mines and the construction project of staff quality have laid the foundation for the construction of healthy enterprises in China's coal ， industry. However the development of coal industry in China is unbalanced and insufficient. There are many problems such as a ， general lack of professional talents the exist of a large number of small coal mines and the underprivileged technology of coal ， ， ， mining poor working environment in underground coal mines many occupational hazards in workplace and relatively few special incentive measures for the construction of healthy enterprises in the coal industry. It is recommended that coal ， enterprises with advanced productivity take the lead to demonstrate coal mine industry construction actively promote advanced ， ， and applicable technology and equipment steadily improve the professional level of coal industry workers comprehensively ， ， improve the environment of mining areas strengthen the monitoring and treatment of occupational hazards improve and ， - implement special incentive measures for healthy enterprises and comprehensively promote the high quality development of coal industry and the construction of healthy enterprises. So as to effectively protect the health occupational rights and interests of workers and provide assistance for occupational health work in the new era.

Effects of water-nitrogen coupling on photosynthetic characteristics, yield, water and nitrogen use efficiency for mountain apple trees under surge-root irrigation in Northern Shaanxi area of China.

Taking 7-year-old apple trees (Hanfu) as the test material, an experiment with three irrigation levels including high water (W1, 85%-100%θf, θf was the field water holding capacity), medium water (W2, 70%-85%θf) and low water (W3, 55%-70%θf), and three nitrogen application levels, high (N1, 600 kg·hm-2), medium (N2, 400 kg·hm-2) and low (N3, 200 kg·hm-2), was conducted to investigate the effects of water and nitrogen coupling on photosynthetic characteristics, yield and water and nitrogen utilization of apple trees in mountainous areas under surge-root irrigation (SRI). The results showed that the net photosynthetic rate (Pn), transpiration rate (Tr), stomatal conductance (gs), intercellular CO2 concentration (Ci), leaf instantaneous water use efficiency (WUEi) of apple trees leaves decreased with decreasing nitrogen application rates under the same irrigation amount, but Ci increased. Under the same nitrogen application rate, foliar Pn, Tr, gs and WUEi decreased with decreasing irrigation amount, but Ci increased. The daily average values of Pn and Tr under W1N1 treatment were the largest, while W2N2 treatment had the largest WUEi. Apple yield, irrigation water use efficiency (IWUE) and nitrogen partial productivity (NPFP) were significantly affected by irrigation and nitrogen application. The W2N2 treatment had the highest yield (26761 kg·hm-2). IWUE increased significantly with the decreasing irrigation and the increasing nitrogen application, while NPFP increased significantly with the increases of irrigation and the decreases of nitrogen application. Results of the regression analysis showed that the combination of irrigation and nitrogen application was closest to W2N2 treatment when yield and IWUE got the optimal solution. Therefore, W2N2 treatment was the best combination mode of water and nitrogen application for apple under SRI in Northern Shaanxi mountain area.

Using Integrated Bioinformatics Analysis to Identify Abnormally Methylated Differentially Expressed Genes in Hepatocellular Carcinoma.

OBJECTIVE: For the identification of abnormally methylated differentially expressed genes (MDEGs) in hepatocellular carcinoma (HCC), this study integrated four microarray datasets to investigate the fundamental mechanisms of tumorigenesis. METHODS: We obtained the expression (GSE76427, GSE57957) and methylation (GSE89852, GSE54503) profiles from Gene Expression Omnibus (GEO). The abnormally MDEGs were identified by using R software. We used the clusterProfiler package for the functional and pathway enrichment analysis. The String database was used to build the protein-protein interaction (PPI) network and visualize it in Cytoscape. MCODE was employed in the module analysis. Additionally, Gene Expression Profiling Interactive Analysis (GEPIA) and The Cancer Genome Atlas (TCGA) were employed to validate results. Lastly, we used cBioPortal software to examine the hub genetic alterations. RESULTS: We identified 162 hypermethylated, down-regulated genes and 190 hypomethylated, up-regulated genes. Up-regulated genes with low methylation were enriched in biological processes, such as keratinocyte proliferation, and calcium homeostasis. Pathway analysis was enriched in the AMPK and PI3K-Akt signaling pathways. The PPI network identified PTK2, VWF, and ITGA2 as hypomethylated, high-expressing hub genes. Down-regulated genes with high methylation were related to responses to peptide hormones and estradiol, multi-multicellular organism process. Pathway analysis indicated enrichment in camp, oxytocin signaling pathways. The PPI network identified CFTR, ESR1, and CXCL12 as hypermethylated, low-expressing hub genes. Upon verification in TCGA databases, we found that the expression and methylation statuses of the hub genes changed significantly, and it was consistent with our results. CONCLUSION: The novel abnormally MDEGs and pathways in HCC were identified. These results helped us further understand the molecular mechanisms underlying HCC invasion, metastasis, and development. Hub genes can serve as biomarkers for an accurate diagnosis and treatment of HCC, and PTK2, VWF, ITGA2, CFTR, ESR1, and CXCL12 are included.

Exosomal connexin 43 regulates the resistance of glioma cells to temozolomide.

Glioblastoma is the most common and aggressive brain tumor and it is characterized by a high mortality rate. Temozolomide (TMZ) is an effective chemotherapy drug for glioblastoma, but the resistance to TMZ has come to represent a major clinical problem, and its underlying mechanism has yet to be elucidated. In the present study, the role of exosomal connexin 43 (Cx43) in the resistance of glioma cells to TMZ and cell migration was investigated. First, higher expression levels of Cx43 were detected in TMZ­resistant U251 (U251r) cells compared with those in TMZ­sensitive (U251s) cells. Exosomes from U251s or U251r cells (sExo and rExo, respectively) were isolated. It was found that the expression of Cx43 in rExo was notably higher compared with that in sExo, whereas treatment with rExo increased the expression of Cx43 in U251s cells. Additionally, exosomes stained with dioctadecyloxacarbocyanine (Dio) were used to visualized exosome uptake by glioma cells. It was observed that the uptake of Dio­stained rExo in U251s cells was more prominent compared with that of Dio­stained sExo, while 37,43Gap27, a gap junction mimetic peptide directed against Cx43, alleviated the rExo uptake by cells. Moreover, rExo increased the IC50 of U251s to TMZ, colony formation and Bcl­2 expression, but decreased Bax and cleaved caspase­3 expression in U251s cells. 37,43Gap27 efficiently inhibited these effects of rExo on U251s cells. Finally, the results of the wound healing and Transwell assays revealed that rExo significantly enhanced the migration of U251s cells, whereas 37,43Gap27 significantly attenuated rExo­induced cell migration. Taken together, these results indicate the crucial role of exosomal Cx43 in chemotherapy resistance and migration of glioma cells, and suggest that Cx43 may hold promise as a therapeutic target for glioblastoma in the future.

Paeonol exerts anti­tumor activity against colorectal cancer cells by inducing G0/G1 phase arrest and cell apoptosis via inhibiting the Wnt/ß­catenin signaling pathway.

Paeonol is a simple phenolic compound isolated from herbal root bark, which has been reported to possess numerous biological and pharmacological characteristics, including a desirable anti­tumor effect. To date, the effect of paeonol against colorectal cancer (CRC) cells is yet to be fully elucidated. Therefore, the present study aimed to identify the underlying mechanism via which paeonol exerts its anti­tumor activity on HCT116 cells. After incubation with various concentrations of paeonol (7.8125, 15.625, 31.25, 62.5, 125, 250 and 500 µg/ml), the inhibitory effect of paeonol on cell viability was assessed using a Cell Counting Kit­8 assay. Cell apoptosis and cell cycle distribution were measured using flow cytometry. Moreover, caspase activity was measured using a colorimetric caspase assay. Luciferase assay was also used to determine the ß­catenin­mediated transcriptional activity of T­cell specific transcription factor/lymphoid­enhancer binding factor (TCF/LEF), and western blotting analysis was performed to measure the related expression of proteins. The results indicated that paeonol exhibited a notable effect against HCT116 cells by inducing G0/G1­phase arrest, as demonstrated by downregulation of the cell cycle regulators cyclin­dependent kinase 4 and cyclin D1 and upregulation of p21Cip1 in a dose­dependent manner. Furthermore, paeonol dose­dependently induced cell apoptosis, accompanied by an increase in the Bax/Bcl­2 ratio, release of cytochrome c and further activation of caspases. Paeonol also dose­dependently blocked the activation of the Wnt/ß­catenin signaling pathway by suppressing the expression of ß­catenin, resulting in a decrease in ß­catenin­mediated activity of TCF/LEF and downregulation of downstream target genes, including cyclin D1, survivin and c­Myc. Therefore, the present results suggested that paeonol exerted its anti­tumor effects on CRC cells, including the inhibition of cell proliferation, induction of cell cycle arrest and initiation of apoptosis, at least partly by suppressing the Wnt/ß­catenin pathway, which may offer a promising therapeutic strategy for CRC.

New phenotype of DCTN1-related spectrum: early-onset dHMN plus congenital foot deformity.

OBJECTIVE: To describe the clinical and genetic features of two patients with different phenotypes due to various Dynactin 1 (DCTN1) gene mutations and further explore the phenotype-genotype relationship. METHODS: Patient 1 is a 23-year-old man with congenital foot deformity and life-long distal muscle weakness and atrophy. Patient 2 is a 48-year-old woman with adult-onset progressive weakness, lower limbs atrophy, and pyramid bundle signs. Electrophysiology test showed normal nerve conduction velocity of both patients and neurogenic changes in needle electromyography. Open sural nerve biopsy for Patient 1 showed slight loss of myelinated nerve fibers. Both patients were performed with whole-exome sequencing followed by functional study of identified variants. RESULTS: Two mutations in DCTN1 gene were identified in Patient 1 (c.626dupC) and Patient 2 (c.3823C>T), respectively. In vitro, the wild type mostly located in cytoplasm and colocalized with α-tubulin. However, c.626dupC tended to be trapped into nuclear and the c.3823C>T formed cytoplasmic aggregates, both losing colocalization with α-tubulin. Western blotting showed a truncated mutant with less molecular weight of c.626dupC was expressed. INTERPRETATION: We identify two novel DCTN1 mutations causing different phenotypes: (1) early-onset distal hereditary motor neuropathy plus congenital foot malformation and (2) amyotrophic lateral sclerosis, respectively. We provide the initial evidence that foot developmental deficiency probably arises from subcellular localizing abnormality of Dynactin 1, revealing DCTN1-related spectrum is still expanding.

Recollecting Cross-Cultural Evidences: Are Decision Makers Really Foresighted in Iowa Gambling Task?

The Iowa Gambling Task (IGT) has become a remarkable experimental paradigm of dynamic emotion decision making. In recent years, research has emphasized the "prominent deck B (PDB) phenomenon" among normal (control group) participants, in which they favor "bad" deck B with its high-frequency gain structure-a finding that is incongruent with the original IGT hypothesis concerning foresightedness. Some studies have attributed such performance inconsistencies to cultural differences. In the present review, 86 studies featuring data on individual deck selections were drawn from an initial sample of 958 IGT-related studies published from 1994 to 2017 for further investigation. The PDB phenomenon was found in 67.44% of the studies (58 of 86), and most participants were recorded as having adopted the "gain-stay loss-randomize" strategy to cope with uncertainty. Notably, participants in our sample of studies originated from 16 areas across North America, South America, Europe, Oceania, and Asia, and the findings suggest that the PDB phenomenon may be cross-cultural.