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Sperm gain fertilization ability and forward movement characteristics during epididymal transport. Sperm maturation is inseparable from the processing of the epididymis. Compared with other reproductive organs, relatively little is known about the epididymis. However, with the development of molecular biology and the improvement of single-cell sequence technology, we gradually realized that we should re-examine the importance of the epididymis for sperm mat-uration and for the entire male reproductive system. Recently, epididymis related reports have tended to be more regionalized and more refined. We can understand cell distribution and gene expression from the perspective of a single cell. It has been reported that different regions of the epididymis have different functions and different cell compositions, which may be determined by gene expression. Here, we comprehensively reviewed the epididymal studies. From the ana-tomical structure of the epididymis to the division of its regions, we focused on the cell compo-sition and region-specific genes differentially expressed in the epididymis. The gene expression of the epididymis extends to a series of biological processes of sperm in the epididymal cavity, and the serious effects of epididymal diseases on reproduction are discussed. Therefore, the importance of the epididymis in male reproduction is emphasized. With the maturity of single-cell spatial transcriptomics, it is hoped that the technology can be applied to epididymal research and bring about the spatiotemporal landscape of the epididymis at the single-cell level.

Dysregulation of RNA-binding proteins (RBPs) is one of the characteristics of cancer. Investigating the biological functions and molecular mechanisms of abnormal RBPs can help uncover new cancer biomarkers and treatment strategies. To identify oncogenic RBPs in triple-negative breast cancer (TNBC), we employed an in vivo CRISPR screen and a TNBC progression model, which revealed small nuclear ribonucleoprotein polypeptide C (SNRPC), a subunit of the U1 small nuclear ribonucleoprotein particle (U1 snRNP), as a key modulator of TNBC progression. SNRPC was frequently upregulated, which corresponded to poor prognosis in TNBC patients. SNRPC ablation significantly impaired the proliferation, migration and invasion of TNBC cells in vitro and in vivo. In addition, SNRPC was essential for the stability of U1 snRNP and contributed to the RNA Pol II-controlled transcriptional program. Knockdown of SNRPC decreased RNA Pol II enrichment on a subset of oncogenes (TNFAIP2, E2F2 and CDK4) and reduced their expression levels. Furthermore, SNRPC deletion was confirmed to inhibit TNBC progression partially through regulation of the TNFAIP2-Rac1-β-catenin signaling pathway. Taken together, this data suggests that SNRPC plays an oncogenic role in TNBC, is a marker of poor prognosis, and may be a valuable therapeutic target for patients with intractable TNBC.

Brown adipose tissue (BAT) plays a key role in thermogenesis during acute cold exposure. However, it remains unclear how BAT is prepared to rapidly turn on thermogenic genes. Here, we show that damage-specific DNA binding protein 1 (DDB1) mediates the rapid transcription of thermogenic genes upon acute cold exposure. Adipose- or BAT-specific Ddb1 knockout mice show severely whitened BAT and significantly decreased expression of thermogenic genes. These mice develop hypothermia when subjected to acute cold exposure at 4 °C and partial lipodystrophy on a high-fat diet due to deficiency in fatty acid oxidation. Mechanistically, DDB1 binds the promoters of Ucp1 and Ppargc1a and recruits positive transcriptional elongation factor b (P-TEFb) to release promoter-proximally paused RNA polymerase II (Pol II), thereby enabling rapid and synchronized transcription of thermogenic genes upon acute cold exposure. Our findings have thus provided a regulatory mechanism of how BAT is prepared to respond to acute cold challenge.

Background:. Endotoxin tolerance (ET) is a protective phenomenon in which pre-treatment with a tolerance dose of lipopolysaccharide (LPS) leads to dramatically elevated survival. Accumulating evidence has shown that peripheral T cells contribute to the induction of ET. However, what happens to T cell development in the thymus under ET conditions remains unclear. The purpose of this study was to analyze the alterations in thymocyte populations (double-positive [DP] and single-positive [SP] cells) under ET conditions. Methods:. Mice were intraperitoneally injected with LPS at a concentration of 5 mg/kg to establish an LPS tolerance model and were divided into two groups: a group examined 72 h after LPS injection (72-h group) and a group examined 8 days after LPS injection (8-day group). Injection of phosphate-buffered saline was used as a control (control group). Changes in thymus weight, cell counts, and morphology were detected in the three groups. Moreover, surface molecules such as CD4, CD8, CD44, CD69, and CD62L were analyzed using flow cytometry. Furthermore, proliferation, apoptosis, cytokine production, and extracellular signal-regulated kinase (ERK) pathway signaling were analyzed in thymocyte populations. The polymorphism and length of the T-cell receptor (TCR) β chain complementarity-determining region 3 (CDR3) were analyzed using capillary electrophoresis DNA laser scanning analysis (ABI 3730). Results:. Thymus weight and cell counts were decreased in the early stage but recovered by the late stage in a murine model of LPS-induced ET. Moreover, the proportions of DP cells (control: 72.130 ± 4.074, 72-h: 10.600 ± 3.517, 8-day: 84.770 ± 2.228), CD4+ SP cells (control: 15.770 ± 4.419, 72-h: 44.670 ± 3.089, 8-day: 6.367 ± 0.513), and CD8+ SP cells (control: 7.000 ± 1.916, 72-h: 34.030 ± 3.850, 8-day: 5.133 ± 0.647) were obviously different at different stages of ET. The polymorphism and length of TCR β chain CDR3 also changed obviously, indicating the occurrence of TCR rearrangement and thymocyte diversification. Further analysis showed that the expression of surface molecules, including CD44, CD69, and CD62L, on thymocyte populations (DP and SP cells) were changed to different degrees. Finally, the proliferation, apoptosis, cytokine production, and ERK pathway signaling of thymocyte populations were changed significantly. Conclusion:. These data reveal that alterations in thymocyte populations might contribute to the establishment of ET.

BRAFV600E is the most common mutated gene in thyroid cancer and is most closely related to papillary thyroid carcinoma(PTC). We investigated the value of elasticity and grayscale ultrasonography for predicting BRAFV600E mutations in PTC.Methods138 patients with PTC who underwent preoperative ultrasound between January 2014 and 2021 were retrospectively examined. Patients were divided into BRAFV600E mutation-free group (n=75) and BRAFV600E mutation group (n=63). Patients were randomly divided into training (n=96) and test (n=42) groups. A total of 479 radiomic features were extracted from the grayscale and elasticity ultra-sonograms. Regression analysis was done to select the features that provided the most information. Then, 10-fold cross-validation was used to compare the performance of different classification algorithms. Logistic regression was used to predict BRAFV600E mutations.ResultsEight radiomics features were extracted from the grayscale ultrasonogram, and five radiomics features were extracted from the elasticity ultrasonogram. Three models were developed using these radiomic features. The models were derived from elasticity ultrasound, grayscale ultrasound, and a combination of grayscale and elasticity ultrasound, with areas under the curve (AUC) 0.952 [95% confidence interval (CI), 0.914−0.990], AUC 0.792 [95% CI, 0.703−0.882], and AUC 0.985 [95% CI, 0.965−1.000] in the training dataset, AUC 0.931 [95% CI, 0.841−1.000], AUC 0. 725 [95% CI, 0.569−0.880], and AUC 0.938 [95% CI, 0.851−1.000] in the test dataset, respectively.ConclusionThe radiomic model based on grayscale and elasticity ultrasound had a good predictive value for BRAFV600E gene mutations in patients with PTC.

Background Suppurative oesophagitis is a diffuse inflammation of the oesophagus characterized by suppurative exudate or pus formation. Suppurative infections can affect any part of the gastrointestinal tract, most commonly the stomach, with inflammation involving the entire gastric cavity. However, cases extending beyond the cardia or pylorus and involving the oesophagus, small intestine, and colon are rare. Usually such cases are discovered during surgery or autopsy. Case summary We report a rare case of acute suppurative oesophagitis. A 57-year-old man presented at the Emergency Department of our hospital with fever and productive cough. The patient had a significant history of lower oesophageal mucosal frostbite. He was successfully diagnosed and treated with repeated gastroscopy, appropriate antibiotics, and innovative symptomatic treatment. Conclusion Early diagnosis and appropriate treatment of acute suppurative oesophagitis are critical. Nutritional support, postural drainage, and other symptomatic treatments must be considered.

BRAF138 patients with PTC who underwent preoperative ultrasound between January 2014 and 2021 were retrospectively examined. Patients were divided into BRAFEight radiomics features were extracted from the grayscale ultrasonogram, and five radiomics features were extracted from the elasticity ultrasonogram. Three models were developed using these radiomic features. The models were derived from elasticity ultrasound, grayscale ultrasound, and a combination of grayscale and elasticity ultrasound, with areas under the curve (AUC) 0.952 [95% confidence interval (CI), 0.914-0.990], AUC 0.792 [95% CI, 0.703-0.882], and AUC 0.985 [95% CI, 0.965-1.000] in the training dataset, AUC 0.931 [95% CI, 0.841-1.000], AUC 0. 725 [95% CI, 0.569-0.880], and AUC 0.938 [95% CI, 0.851-1.000] in the test dataset, respectively.The radiomic model based on grayscale and elasticity ultrasound had a good predictive value for BRAF

Wheat stripe rust, due to infection by Puccinia striiformis f. sp. tritici (Pst), is a devastating disease that causes significant global grain yield losses. Yr36, which encodes Wheat Kinase START1 (WKS1), is an effective high-temperature adult-plant resistance gene and confers resistance to a broad spectrum of Pst races. We previously showed that WKS1 phosphorylates the thylakoid ascorbate peroxidase protein and reduces its ability to detoxify peroxides, which may contribute to the accumulation of reactive oxygen species (ROS). WKS1-mediated Pst resistance is accompanied by leaf chlorosis in Pst-infected regions, but the underlying mechanisms remain elusive. Here, we show that WKS1 interacts with and phosphorylates PsbO, an extrinsic member of photosystem II (PSII), to reduce photosynthesis, regulate leaf chlorosis, and confer Pst resistance. A point mutation in PsbO-A1 or reduction in its transcript levels by RNA interference resulted in chlorosis and reduced Pst sporulation. Biochemical analyses revealed that WKS1 phosphorylates PsbO at two conserved amino acids involved in physical interactions with PSII and reduces the binding affinity of PsbO with PSII. Presumably, phosphorylated PsbO proteins dissociate from the PSII complex and then undergo rapid degradation by cysteine and aspartic proteases. Taken together, these results demonstrate that perturbations of wheat PsbO by point mutation or phosphorylation by WKS1 reduce the rate of photosynthesis and delay the growth of Pst pathogen before the induction of ROS.

Submucosal tunneling endoscopic septum division (STESD) is an endoscopic minimally invasive technique for treating esophageal diverticulum. The objectives of this study were to evaluate the safety and efficacy of STESD and its impact on patients' quality of life.This study included consecutive patients who underwent STESD for esophageal diverticulum from April 2016 to August 2020 in 2 centers (Zhongshan Hospital, Fudan University and Tianjin First Central Hospital). Esophagogram and endoscopic examination were performed before STESD and 30 days after STESD. Patients completed the 36-item Short Form survey (SF-36) before STESD and 1 year after surgery. Clinical symptoms were assessed via telehealth every 6 months until August 2021. Costamagna and Eckardt scores were used to evaluate changes in symptoms.Twenty-one patients were included. Mucosal injury 1 to 2 cm below the septum occurred in 2 patients. No severe surgical adverse events were observed. Median duration of follow-up was 39 months (range, 12-63). Total SF-36 scores increased from 118.7 ± 18.6 before STESD to 132.4 ± 9.1 at 1 year after the procedure (P = .007). SF-36 subscales of general health (P = .002), vitality (P = .004), social functioning (P = .030), and mental health (P = .020) improved significantly after STESD. The mean Costamagna score decreased from 3.83 ± 1.33 to 1.67 ± 1.51 (P = .010), whereas the mean Eckardt score decreased from 3.50 ± .90 to 1.25 ± 1.76 (P = .002). One patient developed symptom recurrence at 10 months after STESD.STESD is a safe and valid endoscopic minimally invasive surgery for esophageal diverticulum, which can reduce symptoms and improve quality of life.

By employment of an amide-functionalized tetracarboxylic ligand 5,5′-(carbonylbis(azanediyl))-diisophthalic acid (H4cbab), a new polyhedral metal–organic framework (MOF) with the chemical formula of {[InZn2(cbda)2(H2O)2](NMF)3}n (1, NMF = N-methylformamide) has been synthesized under the solvothermal reaction condition. The structural feature was studied via the single crystal X-ray diffraction along with ultimate analysis. This as-prepared MOF shows excellent luminescence performance which can be able to detect Al3+ ions selectively. In aqueous solutions, the detection limitation for Al3+ ion is 0.56 µM, which is significantly below the highest standard of 7.41 µM for Al3+ ion in drinking water that is defined by the World Health Organization (WHO). The protective effect of compound against periodontitis was further explored. The viable cell counts (CFU) number was counted to evaluate the inhibitory effect of compound on bacterial growth. The enzyme linked immunosorbent assay (ELISA) was carried on in order to measure accurately the proportion of inflammatory cytokines in gingival fluid around the implant. The potential binding modes of the synthesized compounds as well as the targeted protein was explored by calculating docking with high accuracy as well as pose scoring process.

Cytochrome P450 2D6 (CYP2D6) and endothelial nitric oxide synthase (eNOS) are important in the cardiovascular disease susceptibility and drug response. The methylation of cytosine in the promoter of genes could influence expression. The interindividual differences of drug response could only be explained partly by the polymorphisms of drug disposition genes. This study was aimed to investigate the genetic and epigenetic polymorphisms of CYP2D6 and eNOS in Chinese Tibetan, Mongolian, Uygur, and Han volunteers. Blood samples were collected from 842 unrelated Chinese healthy subjects (323 Tibetan, 134 Mongolian, 162 Uygur, and 223 Han) for genotyping and part of the DNA samples were subjected to cytosine methylation analysis. Significant genetic and epigenetic interethnic polymorphisms of eNOS and CYP2D6 were found in the four Chinese groups. The 4b-G-T wild-type haplotype of eNOS was the most common in Chinese Tibetan (87.1%), Mongolian (79.9%), Uygur (76.4%), and Han (79.5%), respectively. eNOS T-786C creates a new CpG site and a significantly higher methylation level was found in −786CC than that in −786TC in Chinese Han (P = 0.0485) and total Chinese (P = 0.0104). CYP2D6 A-678 (rs28633410) makes the symmetrical CpG site changed to be an asymmetrical CpA site, and the methylation level of cytosine in the CpG context of G-678A was significantly higher than that in the CpA. The results of the present study could be useful for understanding the interindividual disparity of cardiovascular disease susceptibility and drug response among different Chinese ethnic groups and would provide more evidences for the precise medication of Chinese.

The previous cancer studies were difficult to reproduce since the tumor tissues were analyzed directly. But the tumor tissues were actually a mixture of different cancer cells. The transcriptome of single-cell was much robust than the transcriptome of a mixed tissue. The single-cell transcriptome had much smaller variance. In this study, we analyzed the single-cell transcriptome of 272 colorectal cancer (CRC) epithelial cells and 160 normal epithelial cells and identified 342 discriminative transcripts using advanced machine learning methods. The most discriminative transcripts were LGALS4, PHGR1, C15orf48, HEPACAM2, PERP, FABP1, FCGBP, MT1G, TSPAN1 and CKB. We further clustered the 342 transcripts into two categories. The upregulated transcripts in CRC epithelial cells were significantly enriched in Ribosome, Protein processing in endoplasmic reticulum, Antigen processing and presentation and p53 signaling pathway. The downregulated transcripts in CRC epithelial cells were significantly enriched in Mineral absorption, Aldosterone-regulated sodium reabsorption and Oxidative phosphorylation pathways. The biological analysis of the discriminative transcripts revealed the possible mechanism of colorectal cancer.

Cellular retinoic acid binding protein 2 (CRABP2) is essential to myoblast differentiation. However, there was no report about the function of CRABP2 gene in cattle. This study explored the association of CRABP2 gene polymorphisms with growth traits in cattle breeds by several methods, such as DNA sequencing, PCR, PCR-RFLP and forced PCR-RFLP. Two sequence variants were determined. There were 621 individuals in six cattle breeds from China for the experiment, and three breeds were used to test validation of polymorphisms and extent of linkage disequilibrium (LD). The results showed that both SNPs (SNP1, g.2458 G > T, SNP2, g.3878 G > A) were in intron1. Two SNPs were in low linkage disequilibrium. Association analysis suggested that SNP1 had the significant difference on growth traits with body height, height at hip cross and body slanting length (P < .05), while SNP2 showed a significant difference in growth traits with body height, height at hip cross and body slanting length(P < .05). The results of this investigation displayed that the CRABP2 gene is an available candidate gene and may be used for breed selection and conservation.

A concise strategy for the synthesis of vinylsilanes from an iron-catalyzed regio- and stereoselective hydrosilylation of terminal alkynes has been developed. The catalyst and reagents are commercially available and easy to handle, providing a simple and practical method for iron-catalyzed anti-Markovnikov hydrosilylation with a good functional group tolerance.

Deoxynivalenol (DON) and zearalenone (ZEA), which are commonly found in feed products, exhibit serious negative effects on the reproductive systems of domestic animals. However, the toxicity of mycotoxins on the uterine function of donkey (Equus asinus) remains unclear. This study investigated the biological effects of DON and ZEA exposure on donkey endometrial epithelial cells (EECs). It was administered 10 μM and 30 μM DON and ZEA to cells cultured in vitro. The results showed that 10 μM DON exposure markedly changed the expression levels of pyroptosis-associated genes and that 30 μM ZEA exposure changed the expression levels of inflammation-associated genes in EECs. The mRNA expression of cancer-promoting genes was markedly upregulated in cells exposed to DON and 30 μM ZEA; in particular, 10 μM and 30 μM DON and ZEA markedly disturbed the expression of androgen and estrogen secretion-related genes. Furthermore, Q-PCR, Western blot, and immunofluorescence analyses verified the different expression patterns of related genes in DON- and ZEA-exposed EECs. Collectively, these results illustrated the impact of exposure to different toxins and concrete toxicity on the mRNA expression of EECs from donkey in vitro.

To detect the level of vascular endothelial growth factor (VEGF) in bone marrow of patients with non-M3 acute leukemia (AL), and estimate its relationship with prognosis.From January 2016 to December 2019, 114 patients with AL in department of Hematology, Wuwei People's Hospital were selected as study group, and 25 healthy volunteers were enrolled as control group. The concentration of VEGF in bone marrow was detected by ELISA. The patients were divided into high and low concentration group according to the level of VEGF. The overall survival (OS) and event-free survival (EFS) were compared among different groups.The level of VEGF in patients with AL was significantly higher than that in the control group. The median OS and EFS in the low concentration group was 34.5 and 32 months, respectively, while, in the high concentration group was 30 and 26 months, respectively. The differences between the two groups were statistically significant (P=0.010). There were significant differences in OS rate (P=0.035) and EFS rate (P=0.026) between low and high concentration group. Multivariate analysis showed that high VEGF concentration was an independent risk factor affecting OS (HR=2.619, 95%CI 1.070-6.406, P=0.035) and EFS (HR=2.221, 95%CI 1.074-4.552, P=0.031) in AL patients.VEGF highly expresses in the bone marrow of patients with AL at initial diagnosis and relapse, and shows adverse effects on the prognosis.急性白血病患者骨髓VEGF高表达及其与预后的相关性分析.检测非M3型急性白血病（AL）患者的骨髓血管内皮生长因子（VEGF）水平，探讨VEGF的表达水平与预后的关系.选取2016年1月至2019年12月在武威市人民医院血液内科住院的AL患者共114例，以本课题组25名健康志愿者为对照组，用ELISA方法分别检测骨髓VEGF的浓度，依据VEGF表达水平进行分组，比较不同组间总生存期（OS）和无事件生存期（EFS）的差异.AL患者VEGF的表达水平明显高于对照组。VEGF低浓度组的中位OS和EFS分别为34.5和32个月，高浓度组分别为30和26个月，比较差异有统计学意义（P=0.010）。VEGF低浓度组与高浓度组的OS率与EFS率比较，差异均有统计学意义（P=0.035，P=0.026）。多因素分析显示，高浓度VEGF是影响患者OS（HR=2.619，95%CI 1.070-6.406，P=0.035）和EFS（HR=2.221，95%CI 1.074-4.552，P=0.031）的独立危险因素.AL患者初诊及复发时骨髓高表达VEGF，并对患者预后产生不良影响.

To explore the regulation effect of myeloid leukemia No.1 Chinese herb medicine prescription combined with chemotherapy on Th17 cells in bone marrow fluid of AML patients, so as to provide guidance for improving AML treatment effect and patients' long-term survival.Seventy patients with AML who were hospitalized in Department of Hematology, Wuwei People's Hospital from April 2017 to August 2019 were selected and enrolled in AML group, 25 healthy volunteers were selected and enrolled in control group; then according to therapeutic regimen, AML patients were divided into 2 groups: combined therapy group (myeloid leukemia NO.1 Chinese herb medicine prescription combined with chemotherapy) and non-combined therapy group (chemotherapy alone). Flow cytometry was used to detect the ratio of CD3The ratio of CD3Th17 cells expression in bone marrow of newly diagnoses and relapsed AML patients significantly increase, and decrease significantly after treatment. Myeloid leukemia No.1 Chinese herb prescription combined with chemotherapy can significantly increase the CR rate and reduce the RL rate for AML.髓白1号方联合化疗对急性髓系白血病患者骨髓中Th17细胞的调控作用研究.探索髓白1号方联合化疗对AML患者骨髓液中Th17细胞的调控作用，为提高AML患者治疗效果与长期生存提供指导.选取2017年4月- 2019年8月在武威市人民医院血液科住院的AML患者70例，并以25名健康志愿者纳入对照组；然后AML患者根据治疗方案分为联合治疗组（髓白1号方联合化疗）和非联合治疗组（单纯化疗）。采用流式细胞术检测骨髓液中CD3初诊及复发的AML患者CD3初诊及复发的AML患者骨髓中Th17细胞的表达水平明显升高，治疗后显著减低。髓白1号方联合化疗治疗AML可明显提高CR率，降低复发率.

Focusing on the problems of low utilization rate and high cost of laser cladding material, recycled turning machining scrap were used as cladding material to prepare 30CrMnSi laser cladding layer on the surface of 30CrMnSi substrate. The microstructure, hardness, corrosion resistance and wear resistance of 30CrMnSi cladding layer and 30CrMnSi substrate were investigated. Results show that the microstructure of 30CrMnSi cladding layer and 30CrMnSi substrate is mainly dendritic structure and martensite structure respectively, meanwhile, the substrate material presents more pores. The hardness of the laser cladding layer is higher than that of the substrate material due to the fast heating and fast cooling characteristics, and the corrosion resistance of the laser cladding layer is higher than that of the substrate material due to the higher hardness and lower porosity. Therefore, the method adopted in this paper perfectly meets the requirements of green manufacturing and saving resources.

Obesity has become a global pandemic. Identification of key factors in adipogenesis helps to tackle obesity and related metabolic diseases. Here, we show that DDB1 binds the histone reader BRWD3 to promote adipogenesis and diet-induced obesity. Although typically recognized as a component of the CUL4-RING E3 ubiquitin ligase complex, DDB1 stimulates adipogenesis independently of CUL4. A DDB1 mutant that does not bind CUL4A or CUL4B fully restores adipogenesis in DDB1-deficient cells. Ddb1+/- mice show delayed postnatal development of white adipose tissues and are protected from diet-induced obesity. Mechanistically, by interacting with BRWD3, DDB1 is recruited to acetylated histones in the proximal promoters of ELK1 downstream immediate early response genes and facilitates the release of paused RNA polymerase II, thereby activating the transcriptional cascade in adipogenesis. Our findings have uncovered a CUL4-independent function of DDB1 in promoting the transcriptional cascade of adipogenesis, development of adipose tissues, and onset of obesity.

Background Gastroesophageal reflux disease (GERD) is strongly associated with sleep disturbances. Proton pump inhibitors (PPIs) are the main treatment to improve the symptom of GERD. This study was to investigate the efficacy of PPIs on nighttime GERD symptoms and associated sleep disturbances in general Chinese GERD population. Methods Adult patients with mild or more serious nighttime GERD symptoms were included. The efficacy was evaluated by the relief rate of nighttime GERD symptoms and GERD-related sleep disturbances after 4 weeks PPIs treatment. Sleep quality was evaluated using the Pittsburgh Sleep Quality Index Score (PSQI). Results A total of 750 patients were included in the final analysis. Overall, 51.3% of the patients had achieved a relief of nighttime GERD symptoms after 4 weeks of PPIs treatment. By week 4, the percentages of patients with completely resolved nighttime GERD symptoms and GERD-related sleep disturbances were 32.5% and 51.5%, respectively. PSQI score was significantly improved from 6.82 ± 0.12 at baseline to 4.56 ± 0.09 at 4 weeks (P༜0.001). Conclusion PPIs treatment can provide an effective relief of nighttime GERD symptoms and associated sleep disturbances, improving sleep quality of general GERD patients in northern China. Trial registration: Trial registration: CHiCTR, ChiCTR1800017652. Registered 08 August 2018, http://chictr.org.cn/index.aspx

To explore the anatomical features of the external branch of the superior laryngeal nerve (EBSLN) and determine an effective approach for its preservation during endoscopic thyroidectomy (ET).From January 2017 to December 2018, a total of 405 consecutive patients with thyroid disease were retrospectively analyzed. These patients were divided into the ET group and the open thyroidectomy (OT) group according to the surgical approaches. There were 195 cases in the ET group including 43 males and 152 females, and 210 cases in the OT group including 65 males and 145 females. The dissection process of EBSLN, detection rate, distribution of identification methods of the EBSLN and rate of voice change were recorded.There were 205 EBSLNs detected under direct vision in ET group for a detection rate of 88.0%, while 158 EBSLNs were detected under direct vision in OT group for a detection rate of 58.1%. But with the assistant of intraoperative neuromonitoring (IONM), the number of EBSLNs detected visually reached up to 220 in ET group and 226 in OT group, respectively, for a visual detection rate of 94.4% and 83.1%, respectively. There were significant difference in the rate of direct visual identification, total visual identification with IONM. Stratified risk estimation indicated that the tumor size and location were risk factors for the direct visual dissection of EBSLN. Stratified analysis by tumor size indicated that when tumor diameter was ≤ 4 cm, the incidence of vocal cord fatigue and total vocal changes in ET group was significantly lower than that in OT group.Recognition and exposure of the EBSLN can be facilitated by the magnification and focusing function of high-definition endoscopy and the advantage of a 30° variable angle. Full exposure of the sternothyroid-laryngeal triangle and fine dissection along the superior thyroid vessels is beneficial for recognizing the EBSLN.

A convenient and efficient Pd(acac)2/Xantphos-catalyzed regioselective hydrosilylation of allenes has been developed. This convenient catalyst proved to be suitable for a broad range of allenes, offering a general and efficient route to branched allylsilanes in high yields with exceptional regioselectivity. A Pd(0) species involved mechanism is proposed.

A porous organic polymer (POL-Xantphos) was synthesized and employed as a heterogeneous ligand for selective hydrosilylation of alkynes. It exhibits high selectivity and catalytic efficiency toward a broad range of alkynes. Owing to the confinement effect of the micropore structure, POL-Xantphos was far superior to the monomeric Xantphos ligands in controlling the selectivity. By performing hydrosilylation in a flow reactor system, separation and regeneration of the Ni/POL-Xantphos catalyst are easily achieved without any loss in selectivity or activity.

A Co(acac)2 /POL-Xantphos@10PPh3 -catalyzed hydrosilylation of unsymmetrical internal alkynes with Ph2 SiH2 has been developed for the synthesis of highly selective syn-α-vinylsilane products. Furthermore, terminal alkynes were also used and gave the products with excellent regioselectivity and a wide functional group tolerance. Because this porous organic polymer combines the selectivity and activity merits of Xantphos with the stability advantage derived from the high concentration of PPh3 , the Co(acac)2 /POL-Xantphos@10PPh3 can be recycled multiple times without loss of activity and selectivity. This heterogeneous catalyst is expected to find promising applications in industrial synthesis.

RNA interference (RNAi) has been developed for plant pest control. In this study, hairpin-type double-stranded RNA (dsRNA) targeting the juvenile hormone (JH) acid methyltransferase ( JHAMT) gene ( dsJHAMT) was introduced in potato plants via Agrobacterium-mediated transformation. The results indicated that the transcriptional RNA of dsJHAMT accumulated in the transgenic plants. The transcripts and proteins of the L. decemlineata JHAMT gene were significantly reduced in larvae feeding on dsJHAMT transgenic foliage. The dsJHAMT had a significant negative effect on the growth and development of L. decemlineata, especially resulting in less oviposition. Importantly, in the field trials, transgenic plants are high-efficiently protected from insect damage mainly because surviving insects laid fewer or no eggs. Even full protection from beetle damage can be acquired by continuously lowering insect population size at large scale in the field over the years. Therefore, the transgenic plants expressing dsJHAMT successfully provided an additional option for plant pest control.

Zearalenone (ZEA) is one of mycotoxins which are from corn, sorghum and wheat. As an estrogenic compound, ZEA mainly affects animal growth and reproduction with causing abnormal reproduction capability. Previous studies have shown that ZEA poses adverse effects on follicular development, but the mechanism of genetic toxicity of ZEA is not understood. The purpose of this study was to explore the effects of ZEA exposure on granulosa cells which play vital roles during follicular development. Mouse granulosa cells were exposed to 10 μM or 30 μM ZEA for 72 h in vitro, and the differences in gene expression patterns between control and ZEA exposures were analyzed by RNA-seq. The data demonstrated that 30 μM ZEA had a significant effect on the gene expression, especially ZEA exposure increased the expression of many genes related to different kinds of cancers and cancer related pathways like Hippo signaling pathway and the related genes, such as Ccnd1, Smad3, Tead3, Yap1 and Wwtr1. Furthermore, immunohistochemistry confirmed the increase in the protein levels of YAP1, WWTR1 and CCND1 in 30 μM ZEA exposure group. Collectively, this investigation indicated that ZEA exposure promoted the expression of tumorigenesis genes in mouse granulosa cells to.

Zearalenone (ZEA), a natural contaminant found in feed, has been shown to have a negative impact on domestic animal reproduction, particularly in pigs. There are species-specific differences in the ZEA-induced toxicity pattern. Here, we investigated the different biological effects of ZEA exposure on porcine and mouse granulosa cells, using RNA-seq analysis. We treated murine and porcine granulosa cells with 10 μM and 30 μM ZEA during 72 h of culturing, in vitro. The results showed that 10 μM ZEA exposure significantly altered mitosis associated genes in porcine granulosa cells, while the same treatment significantly altered the steroidogenesis associated genes in mouse granulosa cells. Exposure to 30 μM ZEA resulted in significantly up-regulated expression of inflammatory related genes in porcine granulosa cells as well as the cancer related genes in mouse granulosa cells. Similarly, 30 μM ZEA exposure significantly decreased the expression of tumor suppressor factors in the mouse granulosa cells. Furthermore, immunofluorescence, RT-qPCR as well as western-blot analysis verified the different expression of related genes in ZEA exposed porcine and mouse granulosa cells. Collectively, these results illustrate the presence of species differences with regards to ZEA effects between porcine and mouse ovarian granulosa cells, in vitro.

Mizolastine is a selective histamine H1 receptor antagonist for chronic urticaria or allergic rhinitis. We investigated whether the variant genotypes of metabolic enzymes UGT1A1, CYP3A5 and transporter ABCB1 influence pharmacokinetic phenotype of substrate mizolastine in Chinese volunteers. Genotyping of single nucleotide polymorphisms in UGT1A1*6 (G211A), CYP3A5*3 (A6986G) and ABCB1 (C3435T) was determined by the pyrosequencing method. After a single oral dose of 10 mg mizolastine, the plasma concentrations were measured using validated high-performance liquid chromatography in 24 Chinese healthy volunteers. The results showed that the distributions of wild-type homozygotes and variant allele carriers (the sum of variant heterozygotes and variant homozygotes) were as follows: 17 cases (70.8%) versus seven cases (29.2%) in UGT1A1*6 genotypes, five cases (20.8%) versus 19 cases (79.2%) in CYP3A5*3 genotypes and seven cases (29.2%) versus 17 cases (70.8%) in ABCB1 3435T genotypes, respectively. There were no significant differences in pharmacokinetic parameters of mizolastine between the variant allele UGT1A1*6, CYP3A5*3 and ABCB1 3435T carriers and the wild-type homozygotes, and the ratios were as follows: Cmax was 101.03%, 86.02% and 105.78%; Tmax was 162.35%, 98.98% and 144.90%; AUC0-28 was 113.04%, 77.35% and 112.71%; and t1/2 was 95.77%, 72.40% and 100.97%, respectively. In conclusion, these results suggested that the UGT1A1, CYP3A5 and ABCB1 genetic polymorphisms might be not contributed to the interindividual variation of mizolastine pharmacokinetic phenotype in the Chinese population.

Despite numerous experimental studies of the NOx emission of coke combustion, there is no good computational model for NOx emission of the coke combustion. In this study, experimental studies of exhaust emissions of coke combustion were conducted by using micro-sinter equipment. Unreacted-core model was applied to kinetic analysis. The calculated NOx content curve described the measured data well, and the peak and integral total NOx difference values between the calculated and experimental data were 2.7 ppm and 0.15 mL, respectively, which illustrated successful application of unreacted-core model for the NOx emission of coke combustion. The equation also illustrated that particle size of coke breeze and O2 concentration had a great influence on the NOx emission of coke combustion.

(1) Background: Deoxynivalenol (DON) and zearalenone (ZEA) are type B trichothecene mycotoxins that exert serious toxic effects on the reproduction of domestic animals. However, there is little information about the toxicity of mycotoxins on testis development in Equus asinus. This study investigated the biological effects of DON and ZEA exposure on Sertoli cells (SCs) of Equus asinus, (2) Methods: We administered 10 μM and 30 μM DON and ZEA to cells cultured in vitro, (3) Results: The results showed that 10 μM DON exposure remarkably changed pyroptosis-associated genes and that 30 μM ZEA exposure changed inflammation-associated genes in SCs. The mRNA expression of cancer-promoting genes was remarkably upregulated in the cells exposed to DON or 30 μM ZEA, in particular, DON and ZEA remarkably disturbed the expression of androgen and oestrogen secretion-related genes. Furthermore, quantitative RT-PCR, Western blot, and immunofluorescence analyses verified the different expression patterns of related genes in DON- and ZEA-exposed SCs, (4) Conclusions: Collectively, these results illustrated the impact of exposure to different toxins and concrete toxicity on the mRNA expression of SCs from Equus asinus in vitro.

The wetting behavior of sprayed droplets on textured surfaces is the key factor that determines the adhesion strength of sprayed coatings. The 3-D roughness parameter could be used to describe the textured surface and build the relationship with the wettability of sprayed droplets. Micro and nano sale 3-D roughness parameter of surface texture could be acquired separately through the classification extraction due to the micro-nano multiscale roughness feature of laser textured surface. The contact angle of the sprayed droplets at high temperature on a textured surface with different patterns was studied. The results show that the contact angle of the sprayed droplets increases with increases in the amplitude parameter Ssk and the spatial parameter Str, while it decreases with increases in the amplitude parameter Sku and spatial parameter Sal. The nanoscale debris of the laser textured surface are beneficial for improving the amplitude parameter Sku, which can increase the wettability of sprayed particles with the substrates.

Three methods to calculate distribution of internal load in tapered roller bearing are introduced in the present paper. Distributions of internal load in tapered roller bearing used in axle box of High Speed Train have been calculated by continuous function model (conventional method), discrete function model method and finite element method according to the internal load distribution theory of rolling bearing. The results of three methods show that the pattern of the internal load distributions is same, but the accuracy is not same. The accuracy of radial load of the bearing with finite element method is highest, the accuracy with discrete model method is higher and the accuracy with discrete model method is lowest. The discrete function model is not only with the higher accuracy but also convenient to be used widely in practice through the program of dichotomie numerical method.

Pioglitazone is a thiazolidinedione antihyperglycemic drug with insulin-sensitizing properties. We investigated whether the variant genotypes of cytochrome P450 2C8 (CYP2C8), CYP2C9, CYP3A5 and transporter ABCB1 influence the pharmacokinetic phenotype of the substrate pioglitazone in Chinese individuals.Single-nucleotide polymorphisms were determined by the PCR-restriction fragment length polymorphism method in 244 (CYP2C8 and CYP2C9) healthy Chinese Han individuals. After a single oral dose of 30 mg pioglitazone, the plasma concentrations of the parent drug and of two major active metabolites M-III and M-IV were measured using a validated LC-MS/MS in 21 (genotyping CYP3A5 and ABCB1) of these 244 volunteers.The results confirmed that the unique frequencies of CYP2C8*2 (0.0%), CYP2C8*3 (0.0%), and CYP2C9*2 (0.0%) alleles were significantly different from those reported in Whites and Africans, and there were only 10 variant CYP2C9*1/*3 heterozygous (CYP2C9*3 carriers) among 244 Chinese individuals. These results were similar to those reported in Asian ethnic populations, including the Chinese. Unexpectedly, the pioglitazone AUC0-48 in CYP2C9*3 carriers was lower (50.8%), whereas the AUC0-48 ratios of metabolites M-III/pioglitazone and M-IV/pioglitazone increased to 134.3 and 155.8%, respectively, compared with the wild-type CYP2C9*1/*1 homozygous. Moreover, this phenomenon was not observed in individuals with genetic variants of CYP3A5*3 and ABCB1 (C1236T).The present research suggests that the CYP2C8, CYP3A5, and ABCB1 genes play no significant role in the interindividual variation of pioglitazone pharmacokinetics, whereas CYP2C9*3 carriers are likely to accelerate the metabolism of this antidiabetic drug in the Chinese Han ethnic population.

A novel multi-beam folded waveguide (MBFW) circuit, which can enhance the output power and interaction efficiency of sub-terahertz (THz) traveling wave tube (TWT), is presented in the paper. Operating with fundamental mode and multiple electron beams means that a larger beam current can be used for a higher output power. The characteristics of the MBFW structure are analyzed and optimized. Compared with the single-beam folded waveguide (SBFW) TWT, the output power of the MBFW TWT increases from 3.64 W to 25.45 W at 140 GHz and its electronic efficiency increases from 1.06% to 7.4% under the conditions of an input peak power of 10 mW, a beam voltage of 9.55 kV and a current of 12 mA. The optimized MBFW structure can be successfully fabricated by micro milling, with dimension errors below expectation, and the measured transmission characteristics are in good agreement with the design.

To evaluate the effects of a 48-week course of adefovir dipivoxil (ADV) plus Chinese medicine (CM) therapy, namely Tiaogan Jianpi Hexue (调肝健脾和血) and Tiaogan Jiedu Huashi (调肝解毒化湿) fomulae, in hepatitis B e antigen (HBeAg)-positive Chinese patients. A total of 605 HBeAg-positive Chinese CHB patients were screened and 590 eligible participants were randomly assigned to 2 groups in 1:1 ratio including experimental group (EG, received ADV plus CM) and control group (CG, received ADV plus CM-placebo) for 48 weeks. The major study outcomes were the rates of HBeAg and HBV-DNA loss on week 12, 24, 36, 48, respectively. Secondary endpoints including liver functions (enzymes and bilirubin readings) were evaluated every 4 weeks at the beginning of week 24, 36, and 48. Routine blood, urine, and stool analyses in addition to electrocardiogram and abdominal B scan were monitored as safety evaluations. Adverse events (AEs) were documented. The combination therapy demonstrated superior HBeAg loss at 48 weeks, without additional AEs. The full analysis population was 560 and 280 in each group. In the EG, population achieved HBeAg loss on week 12, 24, 36, and 48 were 25 (8.90%), 34 (12.14%), 52 (18.57%), and 83 (29.64%), respectively; the equivalent numbers in the CG were 20 (7.14%), 41 (14.64%), 54 (19.29%), and 50 (17.86%), respectively. There was a statistically significant difference between these group values on week 48 (P

Cellular retinoic acid binding protein 2 (

The regulation of vascular smooth muscle cell (VSMC) proliferation is an important issue due to its major implications for the prevention of pathological vascular conditions. The objective of this work was to assess the function of small ubiquitin-like modifier (SUMO)ylated Krϋppel-like transcription factor 4 (KLF4) in the regulation of VSMC proliferation in cultured cells and in animal models with balloon injury. We found that under basal conditions, binding of non-SUMOylated KLF4 to p300 activated p21 (p21(WAF1/CIP1))transcription, leading to VSMC growth arrest. PDGF-BB promoted the interaction between Ubc9 and KLF4 and the SUMOylation of KLF4, which in turn recruited transcriptional corepressors to the p21 promoter. The reduction in p21 enhanced VSMC proliferation. Additionally, the SUMOylated KLF4 did not affect the expression of KLF4, thereby forming a positive feedback loop enhancing cell proliferation. These results demonstrated that SUMOylated KLF4 plays an important role in cell proliferation by reversing the transactivation action of KLF4 on p21 induced with PDGF-BB.

Cytochrome P450 1A2 (CYP1A2), CYP2B6 and inducible nitric oxide synthase (iNOS) are involved in the metabolism and action of many important therapeutic drugs, and genetic variants have been associated with interethnic differences in response to treatment, including chemotherapy.Eight hundred and forty-two unrelated Chinese healthy subjects (323 Tibetan, 134 Mongolian, 162 Uygur and 223 Han) were recruited for genotyping. Frequencies of CYP1A2 -163CA, CYP2B6 516GT and iNOS -954GC were determined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods.The frequency of CYP1A2-163A was higher in Chinese Mongolian (0·698) than in Chinese Tibetan (0·633), Uygur (0·633) and Han populations (0·608, P0·05), respectively. The frequency of CYP1A2-163A in the Chinese population (total, 0·636) was intermediate between those reported in Caucasians (0·682, P0·05) and Africans (0·549, P0·01). The frequency of CYP2B6 516T in Chinese Uygur (0·287) was significantly higher than those in Chinese Tibetan (0·147, P0·01) and Mongolian (0·179, P0·01), respectively, but was similar to the frequency in Chinese Han (0·226). The frequencies of CYP2B6 516T were in the order of Africans (0·500)Caucasians (0·286)Chinese (0·200). The variant iNOS-954C was rare in Chinese Tibetan (0·005), Mongolian (0·004), Uygur (0·000) and Han (0·007), respectively, but showed higher frequencies in African ethnic groups. The frequencies of iNOS-954C were in the order of Africans (0·098)Chinese (0·004)Caucasians (0·000).This is the first report of the distribution frequencies of functional CYP1A2, CYP2B6 and iNOS genes among mainland Chinese Tibetan, Mongolian, Uygur and Han populations. These results should help inform studies of interethnic differences in disease susceptibility or drug responses.

Present in many plant foods, biogenic phenolic compounds are important bioactive phytonutrients with high anti-oxidant activity and thereby are praised for their health-promoting properties. However, current food nutrient improvement by high phenolic content in staples is limited by the shortage of genetic resources rich in phenolic compounds. To resolve this obstacle, we developed a non-destructive massive analytical approach to screen wheat phenolic mutants. In grains, multiple mutant lines showed significantly higher contents of flavonoids or cell wall-bound phenolic esters. Moreover, five mutants showed higher anti-oxidant potentials in wall-bound phenolic compounds ranging from 15% to 20%, with the maximal close to natural black wheat. In contrast to black wheat, two mutants accumulated higher phenolic compounds in the endosperm. lrf4 was mapped by BSR to a concentrated genomic region in the short arm of chromosome 1A. The present work represents an efficient high-throughput strategy to increase wheat anti-oxidant potential through traditional mutagenesis.

A Co(acac)

Methyl 3-amino-6-methoxythieno [2,3-b] quinoline-2-carboxylate (PU-48) is a novel diuretic urea transporter inhibitor. The aim of this study is to investigate the profile of plasma pharmacokinetics, tissue distribution, and excretion by oral dosing of PU-48 in rats. Concentrations of PU-48 within biological samples are determined using a validated high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. After oral administration of PU-48 (3, 6, and 12 mg/kg, respectively) in self-nanomicroemulsifying drug delivery system (SNEDDS) formulation, the peak plasma concentrations (Cmax), and the area under the curve (AUC0&ndash, &infin, ) were increased by the dose-dependent and linear manner, but the marked different of plasma half-life (t1/2) were not observed. This suggests that the pharmacokinetic profile of PU-48 prototype was first-order elimination kinetic characteristics within the oral three doses range in rat plasma. Moreover, the prototype of PU-48 was rapidly and extensively distributed into thirteen tissues, especially higher concentrations were detected in stomach, intestine, liver, kidney, and bladder. The total accumulative excretion of PU-48 in the urine, feces, and bile was less than 2%. This research is the first report on disposition via oral administration of PU-48 in rats, and it provides important information for further development of PU-48 as a diuretic drug candidate.

Hand, foot, and mouth disease (HFMD) is a common infectious disease in childhood caused by an enterovirus (EV), and which is principally seen in children under 5 years of age. To promote diagnostic awareness and effective treatments, to further standardize and strengthen the clinical management and to reduce the mortality of HFMD, the guidelines for diagnosis and treatment have been developed. National Health Commission of China assembled an expert committee for a revision of the guidelines. The committee included 33 members who are specialized in diagnosis and treatment of HFMD. Early recognition of severe cases is utmost important in diagnosis and treatment of patients with HFMD. The key to diagnosis and treatment of severe cases lies in the timely and accurate recognition of stages 2 and 3 of HFMD, in order to stop progression to stage 4. Clinicians should particularly pay attention to those EV-A71 cases in children aged less than 3 years, and those with disease duration less than 3 days. The following indicators should alert the clinician of possible deterioration and impending critical disease: (1) persistent hyperthermia; (2) involvement of nervous system; (3) worsening respiratory rate and rhythm; (4) circulatory dysfunction; (5) elevated peripheral WBC count; (6) elevated blood glucose and (7) elevated blood lactic acid. For treatment, most mild cases can be treated as outpatients. Patients should be isolated to avoid cross-infection. Intense treatment modalities should be given for those severe cases. The guidelines can provide systematic guidance on the diagnosis and management of HFMD.

Cenchrus spinifex is an invasive plant found in large areas of northern China. In this study, we focused on analysis of the effects of C. spinifex on soil nitrogen and plant nitrogen pools in Horqin sandy grassland. In addition, a pot experiment with以我国北方大面积发生的入侵植物少花蒺藜草为对象,研究了其对科尔沁沙质草地土壤氮库和地上植物氮库的影响,并在室内条件下,以自然生境中少花蒺藜草伴生牧草披碱草和扁穗冰草为对照,利用

Flaveria bidentis is an invasive plant found in large areas of northern China. This study conducted a separation and screening of the main functional bacteria in the soil of F. bidentis and investigated the change in the community structure. A variety of functional microbes were isolated using selective media and rep-PCR clustering, and a diversity analysis was carried out. In addition, the dominant populations of various functional bacteria were identified using 16S rRNA sequence alignment. The results showed that F. bidentis increased the contents of the major available nutrients in the soil, and the levels of azotobacteria, organic phosphorus bacteria, inorganic phosphorus bacteria, and silicate bacteria in the soil of F. bidentis were significantly higher than those of the native plant Tagetes erecta and the control. rep-PCR analysis indicated that the structure of the four functional bacterial microfloras in the soil of F. bidentis was significantly different from those of the native plant and control. The diversity analysis demonstrated that the diversity of functional microorganisms in the soil of F. bidentis was richer, the community structure was more complex, the predominant microflora comprised a greater proportion of the total population, and the ecological diversity was higher. This was further evidenced by identification of the main functional isolates from the three soil samples. Our findings indicated a mechanism of invasion by F. bidentis.以我国北方大面积发生的入侵植物黄顶菊为研究对象,对黄顶菊根际土壤中可培养的主要功能细菌进行了分离筛选,通过rep-PCR聚类和多样性分析研究了其群落结构的变化,并利用16S rRNA序列比对,对主要优势菌群进行鉴定.结果表明: 相对于本地植物万寿菊和空白对照,黄顶菊显著增加了根际土壤中固氮菌、有机磷细菌、无机磷细菌和钾细菌的数量.rep-PCR分析显示,黄顶菊根际4种功能细菌的种群结构与本地植物和对照相比有显著差异,3种土壤中相同的聚类群极少.多样性分析表明,黄顶菊根际微生物物种多样性更加丰富,群落结构更加复杂,优势种群比较明显,生态多样性较高.对从3种土壤中分离得到的主要优势菌群的鉴定结果也进一步证明了这一结论.研究结果为阐明黄顶菊入侵的微生态机制提供了理论基础.