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Parkinson’s disease (PD) is a common neurodegenerative disease characterized by neuronal loss in the substantia nigra. The p75 neurotrophin receptor (p75NTR, encoded by NGFR) was found to play an important role in the selective neuronal death of dopamine neurons in the substantia nigra, as well as the pathogenesis and development of PD. To assess the association between NGFR gene polymorphism and the susceptibility of PD, this case-control study consisting of 414 PD patients and 623 age- and sex-matched controls in a Chinese Han cohort was conducted. Twelve tag-single nucleotide polymorphisms (tag-SNPs) were selected from the NGFR gene through the construction of linkage disequilibrium blocks. One tag-SNP from the ADAM17 gene was also selected owing to its function of encoding tumor necrosis factor α-converting enzyme, which is responsible for the shedding of the extracellular domain of p75NTR. A multiplex polymerase chain reaction-ligase detection reaction (PCR-LDR) method was applied for genotyping. The associations between tag-SNPs and the risk of PD with the adjustment for age and sex were analyzed by unconditional logistic regression, and five genetic models including codominant, dominant, recessive, over-dominant, and additive models were applied. The results showed that among the 13 tag-SNPs, rs741073 was associated with a reduced risk of PD in the codominant (OR = 0.71, 95% CI = 0.54–0.93, P = 0.037), dominant (OR = 0.76, 95% CI = 0.58–0.98, P = 0.033), and over-dominant models (OR = 0.71, 95% CI = 0.54–0.92, P = 0.010), and rs1804011 was also associated with a reduced risk of PD in the codominant (OR = 0.69, 95% CI = 0.50–0.95, P = 0.049), dominant (OR = 0.69, 95% CI = 0.50–0.93, P = 0.014), over-dominant (OR = 0.70, 95% CI = 0.51–0.96, P = 0.025), and additive models (OR = 0.72, 95% CI = 0.54–0.94, P = 0.016). However, these associations did not retain after Bonferroni correction. Conclusively, our study failed to reveal the association between the selected tag-SNPs within NGFR, ADAM17, and the susceptibility of PD. The role of p75NTR and its gene polymorphisms in the pathogenesis of PD needs to be further studied.

Composite hemangioendothelioma (CHE) is a rare vascular neoplasm of intermediate malignant potential. Only 52 cases have been reported in the English literature, and one case previously reported occurred in the spleen. The purpose of our study was to report a 65-year-old man diagnosed as CHE primary arising from the spleen with multiple metastases.Clinical and imaging features, laboratory tests, and pathological results about CHE were described in detail in this study.The patient presented with multiple lesions in bilateral lungs and spleen that had been incidentally detected by computed tomography (CT). Except for thrombocytopenia, other laboratory tests were not significant. The CT scan of the abdomen revealed multiple round-like and irregularly mixed density masses with unclear borders in enlarged spleen. And contrast enhancement showed mild heterogeneous enhancement. CT scan also showed widespread liver, ribs, lungs, and vertebral bodies metastases. This diagnosis was confirmed by histopathological examination. The patient underwent splenectomy and still survives with tumors after six months followed-up.Due to the lack of specificity of clinical features and laboratory tests, it is necessary to combine imaging features and pathological findings to make a correct diagnosis.

Purpose To discuss the value of caudate lobectomy in hilar cholangiocarcinoma (HCCA) treatment. Methods A systematic review was performed in PubMed, MEDLINE database, EMBASE, and Cochrane Library for trials comparing combined caudate lobectomy with controls from January 1, 1990 to December 2, 2020. The outcomes were postoperative radical cure information, survival condition, morbidity, and mortality. Result Ten studies were included. No difference was observed in the morbidity (odd ratio (OR) 0.93, 95% confidence interval (CI) 0.65-1.33) and mortality (OR 1.16, 95% CI 0.55-2.42) between the combined caudate lobectomy and control groups. Hepatectomy combined with caudate lobectomy was associated with higher incidence of radical resection (OR 3.88, 95% CI 2.18-6.90) and longer survival (hazard ratio 0.45, 95% CI 0.38-0.55). Conclusion Combining caudate lobectomy can significantly increase the incidence of radical resection of HCCA and the postoperative survival time. The morbidity and mortality were not increased after the operation. Thus, caudate lobectomy should be included when performing partial hepatectomy for HCCA.

To investigate the relationship between tissue distributions of modified Wuzi Yanzong prescription (加味五子衍宗方, MWP) in rats and meridian tropism theory. A high-performance liquid chromatography with Fourier transform-mass spectrometry (HPLC-FT) method was used to identify the metabolites of MWP in different tissues of rats after continued oral administration of MWP for 7 days. The relationship between MWP and meridian tropism theory was studied according to the tissue distributions of the metabolites of MWP in rats and the relevant literature. Nineteen metabolites, mainly flavanoid compounds, were detected in the different rat tissues and classified to each herb in MWP. Further, it was able to establish that the tissue distributions of the metabolites of MWP were consistent with the descriptions of meridian tropism of MWP available in literature, this result might be useful in clarifying the mechanism of MWP on meridian tropism. In the long run, these data might provide scientific evidence of the meridian tropism theory to further promote the reasonable, effective utilization, and modernization of Chinese medicine. The tissue distributions of MWP in vivo were consistent with the descriptions of meridian tropism of MWP.

Objective: To study the effect of sevoflurane and propofol on cerebral oxygen metabolism in cardiopulmonary bypass (CPB) and postoperative neurological function injury. Methods: A total of 48 cases of patients who received mitral valve replacement under CPB in our hospital were selected and randomly divided into sevoflurane group (S group) and propofol group (P group) who received sevoflurane-based intravenous inhalational anesthesia and propofol-based total intravenous anesthesia respectively, cerebral oxygen metabolism indexes were determined before CPB started (T0), when nasopharyngeal temperature fell to a constant low temperature (T1), when CPB ended (T2) and 1 h after CPB ended (T3) respectively during operation, and serum neurological function, cardiac function and liver function injury molecules were determined after operation. Results: Intraoperative SjvO2, AVDO2, O2ER and rSO2 were not significantly different between two groups, SjvO2 at T1 significantly increased, AVDO2 and O2ER significantly decreased and rSO2 didn’t change significantly, SjvO2 at T2 significantly decreased, AVDO2 and O2ER significantly increased and rSO2 didn’t change significantly; postoperative serum NSE, S100β, Aβ, Glu, Asp and Gly levels of S group were significantly lower than those of P group, and CK-MB, LDH, cTnI, ALT and AST levels were not significantly different from those of P group. Conclusion: Both sevoflurane and propofol can maintain the balance of cerebral oxygen metabolism in mitral valve replacement under CPB and protect the cardiac function and liver function, but sevoflurane has more ideal protective effect on postoperative neurological function.

Increasing evidence suggests that low to moderate ethanol ingestion protects against the deleterious effects of subsequent ischemia/reperfusion; however, the underlying mechanism has not been elucidated. In the present study, we showed that expression of the neuronal large-conductance, Ca2+-activated K+ channel (BKCa) α-subunit was upregulated in cultured neurons exposed to oxygen-glucose deprivation/reoxygenation (OGD/R) compared with controls. Preconditioning with low-dose ethanol (10 mmol/L) increased cell survival rate in neurons subjected to OGD/R, attenuated the OGD/R-induced elevation of cytosolic Ca2+ levels, and reduced the number of apoptotic neurons. Western blots revealed that ethanol preconditioning upregulated expression of the anti-apoptotic protein Bcl-2 and downregulated the pro-apoptotic protein Bax. The protective effect of ethanol preconditioning was antagonized by a BKCa channel inhibitor, paxilline. Inside-out patches in primary neurons also demonstrated the direct activation of the BKCa channel by 10 mmol/L ethanol. The above results indicated that low-dose ethanol preconditioning exerts its neuroprotective effects by attenuating the elevation of cytosolic Ca2+ and preventing neuronal apoptosis, and this is mediated by BKCa channel activation.

Objective: To analyze the protective effect of dexmedetomidine combined with ulinastatin on cardiopulmonary function impairment caused by cardiopulmonary bypass surgery. Methods: A total of 78 patients who received valve replacement under cardiopulmonary bypass were divided into observation group and control group (n=39) according to random number table. Control group received intraoperative ulinastatin intervention and observation group received intraoperative dexmedetomidine combined with ulinastatin intervention. Differences in the levels of cardiac function indexes, myocardial injury markers, pulmonary function parameters, inflammatory indexes and so on were compared between two groups of patients 24 hours after operation. Results: Cardiac function parameters LSV, RSV and RVEF values of observation group 24 hours after operation were higher than those of control group while PAP value was lower than that of control group; serum myocardial injury markers H-FABP, cTn-T, CKMB, cTnⅠ and NT-proBNP levels were lower than those of control group; lung function parameters Cs and Cd values were higher than those of control group while RI, R5-R20, X5 and Fres values were lower than those of control group; serum pro-inflammatory factors IL-6 and TNF-α levels were lower than those of control group while anti-inflammatory factors sTNF-RI, IL-4 and IL-10 levels were higher than those of control group. Conclusions: Dexmedetomidine combined with ulinastatin can protect the cardiopulmonary function in patients with cardiopulmonary bypass, and help to reduce the occurrence of postoperative cardiopulmonary dysfunction and other severe complications.

BackgroundThe purpose of this study is to determine the prognostic significance of pelvic lymph node (PLN) characteristics and perform risk stratification in patients undergoing concurrent chemoradiotherapy for locally advanced cervical squamous cell carcinoma.MethodsWe retrospectively reviewed the records of 609 patients with Federation Internationale de Gynecologie et d’Obstetrique (FIGO) stage II to IVa who underwent concurrent chemoradiotherapy, compared overall survival (OS), distant metastasis-free survival (DMFS), and pelvic recurrence-free survival between patients with or without PLN involvement. We further analyzed prognostic factors for OS and DMFS including FIGO stage, tumor volume, and lymph node (LN) characteristics in 300 patients with PLN involvement.ResultsThe 3-year OS rate was 81.7% versus 92.8% (P = 0.002) and the 3-year DMFS rate was 79.3% versus 92.7% (P = 0.006) in patients with or without PLN involvement, respectively. With univariable analysis, FIGO stage, LN-volume, LN-number, LN-diameter, and matted/necrotic LN affected both OS and DMFS. Based on multivariable analysis, we created a risk stratification model. For OS, the independent risk factors were FIGO stage III or IVa, LN-volume of 3 cm3 or more, LN-diameter of 1.5 cm or more, and matted/necrotic LN. The low-risk group (no risk factors), mid-risk group (1 or 2 risk factors), and high-risk group (3 or 4 risk factors) had a 3-year OS of 96.6%, 84.9%, and 64.7%, respectively (P = 0.005). For DMFS, LN-diameter of 1.5 cm or more, LN-number of 3 or more, and matted/necrotic LN were the independent risk factors. The subgroups for DMFS were the low-risk group (no risk factors), the mid-risk group (1 risk factor), and the high-risk group (2 or 3 risk factors), and the 3-year DMFS was 92.4%, 76.2%, and 64.6%, respectively (P = 0.001).ConclusionsThe prognosis was significantly poorer for patients with high-risk lymph node characteristics. Using this risk stratification, we should select the most appropriate and individualized treatment modality to improve outcomes in those patients with a poorer prognosis.

Melanization mediated by prophenoloxidase (proPO) activating system play an essential role in killing invading microorganisms in invertebrates. Lipopolysaccharide and β-1, 3-glucan binding protein (LGBP) as a pattern recognition protein have been demonstrated to active the proPO cascade in insect and shrimp. In this study, we investigated the role of LGBP in prophenoloxidase cascade-induced melanization in Chinese mitten crab (Eriocheir sinensis). By RT-PCR analysis, EsLGBP was detected in all tested tissues, and showed highest expression in hemocytes, gill, intestine and brain. The expression of EsLGBP was up-regulated in the hemocytes following injections of LPS and β-1, 3-glucan. The recombinant EsLGBP protein (rEsLGBP) was produced via prokaryotic expression system and affinity chromatography. By western blotting, rEsLGBP was discovered to exhibit the ability to bind to all tested microorganisms, including Gram-negative bacteria, Gram-positive bacteria and yeast (Pichia pastoris). Meanwhile we found rEsLGBP has a high binding activity towards microbial immune elicitors such as LPS and β-1, 3-glucan whereas no binding activity is detected with peptidoglycan. Moreover, the effects of RNAi-mediated blockade of EsLGBP were investigated on bacterial counts in the hemolymph and cumulative mortality rate of crabs infected with Vibrio parahaemolyticus in vivo. Further experiments demonstrate that rEsLGBP can trigger the whole hemolymph dependent melanization and stimulate to proPO cascade in vitro. Taken together, these results provide experimental evidence for role of LGBP in innate immunity, especially in the activation of prophenoloxidase activating system.

C-type lectins (CTLs) are pattern recognition proteins that play significant roles in the innate immune system by identifying and eliminating pathogens. Here, we have reported a CTL (EsLecH) from the Chinese mitten crab that can bind to microorganisms and regulate antimicrobial peptide (AMP) expression via the c-Jun N-terminal kinase (JNK) pathway. EsLecH was found to have an N-terminal signal peptide and a single carbohydrate recognition domain. The EsLecH transcript was detected abundantly in various tissues, and it was significantly upregulated in hemocytes after challenging with lipopolysaccharides and bacteria. Recombinant (r)EsLecH could bind to microorganisms, but at different levels. Ca(2+) significantly increased rEsLecH binding affinity to microorganisms. Furthermore, growth inhibition by rEsLecH increased with increasing rEsLecH levels. Knockdown of EsLecH was accompanied by a significant reduction in AMP expression and JNK phosphorylation; AMP expression was reduced with JNK silencing and can not rescued by rEsLecH when absence of JNK. These results indicate that EsLecH could regulate AMPs via JNK signaling.

Melanoma is a type of cancer arising from the melanocytes, which are the cells that make up the pigment melanin and are derived from the neural crest. There is no particularly effective therapy once the disease is metastatic, highlighting the need for discovery of novel potent agents. In this investigation, we adopted a zebrafish embryonic pigmentation model to identify antimelanoma agents by screening an in-house small molecule library. With this assay, we found that a small molecule compound, SKLB226, blocked zebrafish pigmentation and pigment cell migration. Mechanism of action studies showed that SKLB226 downregulated MITF mRNA level in both zebrafish embryos and mammalian melanoma cells. Further studies showed that it could efficiently suppress the viability and migration of mammalian melanoma cells. In summary, SKLB226 can be used as a chemical tool to study melanocyte development as well as an antimelanoma lead compound that should be subjected to further structural optimization.

// Weijun Jiang 1 , Jing Zhang 1 , Qing Zhou 1 , Shuaimei Liu 1 , Mengxia Ni 1 , Peiran Zhu 1 , Qiuyue Wu 1 , Weiwei Li 1 , Mingchao Zhang 1 , Xinyi Xia 1 1 Department of Reproduction and Genetics, Institute of Laboratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, P.R. China Correspondence to: Xinyi Xia, e-mail: xiaxynju@163.com Keywords: androgen receptor, GGN repeat, CAG repeat, testicular cancer, polymorphism Received: October 22, 2015 Accepted: January 29, 2016 Published: February 12, 2016 ABSTRACT The risk of testicular cancer (TC) is markedly increased in subjects with androgen insensitivity, and previous studies have proposed that GGN and CAG repeats in androgen receptors ( AR ) could be related to the risk of TC. To evaluate the association between the length of GGN and CAG repeats in AR and TC, a meta-analysis involving 3255 TC cases and 2804 controls was performed. The results suggested that long GGN repeats are associated with an increased risk of TC compared with those 200, and in the mid-latitude, and seminoma subgroups. The subgroup analysis based on populations, high-latitude, and seminomas/non-seminomas suggested that AR CAG repeat polymorphisms with > 25 and 25 repeats might confer a protective effect to the patients with TC (in the high-latitude subgroup analysis, for > 25 vs . 21–25: OR = 0.54, 95% CI = 0.41–0.70). In contrast, an increased risk of TC was observed for AR CAG repeat polymorphisms with > 25 and 25 repeats in the mid-latitude subgroup (for > 25 vs . 21–25: OR = 1.65, 95% CI = 1.09–2.50). In addition, no associations between the remaining subgroups and male infertility were observed. In short, this meta-analysis suggested that AR GGN and CAG repeat polymorphisms may be involved in the etiology of TC.

Flavonol derivatives are a group of flavonoids benefiting human health. Their abundant presence in tea is associated with astringent taste. To date, mechanism pertaining to the biosynthesis of flavonols in tea plants remains unknown. In this study, we used bioinformatic analysis mining the tea genome and obtained three cDNAs that were annotated to encode flavonol synthases (FLS). Three cDNAs, namely CsFLSa, b, and c, were heterogenously expressed in E. coli to induce recombinant proteins, which were further used to incubate with three substrates, dihydrokampferol (DHK), dihydroquercetin (DHQ), and dihydromyricetin (DHM). The resulting data showed that three rCsFLSs preferred to catalyze (DHK). Overexpression of each cDNA in tobacco led to the increase of kampferol and the reduction of anthocyanins in flowers. Further metabolic profiling of flavan-3-ols in young tea shoots characterized that kaempferol derivatives were the most abundant, followed by quercetin and then myricetin derivatives. Taken together, these data characterized the key step committed to the biosynthesis of flavonols in tea leaves. Moreover, these data enhance understanding the metabolic accumulation relevance between flavonols and other main flavonoids such as flavan-3-ols in tea leaves.

Diabetic encephalopathy (DE) is a serious complication caused by long-term cognitive impairment in diabetic patients. At present, there is no effective treatment for DE. Icariin (ICA) is a bioactive ingredient isolated from Epimedium. Previous research indicated that ICA was neuroprotective against Aβ-induced PC12 cell insult; however, the effect of ICA on an advanced glycosylation end product- (AGE-) induced neural injury model has not been studied. In this study, we investigated the neuroprotective effects of ICA on AGE-induced injury in PC12 cells. Our findings revealed that ICA could effectively protect PC12 cells from AGE-induced cell apoptosis by suppressing oxidative stress. Moreover, we observed that ICA could significantly protect against mitochondrial depolarization following AGE stimulation and inactivate the mitochondria-dependent caspase-9/3 apoptosis pathway. Most notably, we identified the direct target protein of ICA as apoptosis regulator Bax by a pulldown assay. We found that ICA could specifically target Bax protein and inhibit Bax dimer formation and migration to mitochondria. Furthermore, a siRNA knockdown experiment revealed that ICA could inhibit PC12 cell apoptosis and oxidative stress through targeting Bax. Taken together, our findings demonstrated that ICA could attenuate AGE-induced oxidative stress and mitochondrial apoptosis by specifically targeting Bax and further regulating the biological function of Bax on mitochondria.

Granular computing serves as a general framework for complex problem solving in broad scopes and at various levels. The granularity was constructed via many ways, however, for complex systems there remain two challenges including determining a reasonable granularity and extracting the hierarchical information. In this paper, a new method is presented for constructing the optimal hierarchical structure based on fuzzy granular space. Firstly, the inter-class deviations and intra-class deviations were introduced, whose properties were investigated in depth and approved mathematically. Secondly, the fuzzy hierarchical evaluation index is developed, followed with a novel model for extracting the global optimal hierarchical structure established. An algorithm is then proposed, which reliably constructs the multi-level structure of complex system. Finally, to reduce the complexity, the granular signatures are extracted according to the nearest-to-center principle; with the use of the signatures, a classifier is designed for verifying our method. The validation of this method is approved by an application to the H1N1 influenza virus system. The theories and methodologies on granular computing presented here are helpful for capturing the structural information of complex system, especially for data mining and knowledge discovery.

Iron homeostasis is vital to organismal health; it is maintained by the iron regulatory protein (IRP)-iron-responsive element (IRE) signaling pathway. In the Chinese mitten crab Eriocheir sinensis, EsFer-1 and EsFer-2 reportedly have a putative IRE, but an IRP has not yet been identified. In this study, we successfully amplified the full-length cDNA of EsIRP using gene cloning and rapid amplification of cDNA ends techniques. The length of this cDNA was 4474 bp, and it included a 2682-bp open reading frame encoding 893 amino acids. Using quantitative real-time PCR, mRNA transcripts of EsIRP were detected in various tissues. The highest and lowest expression level was detected in the muscle and gills, respectively. In response to Staphylococcus aureus and Vibrio parahaemolyticus challenge, the transcription level of EsIRP was downregulated and that of EsFer-1 and EsFer-2 was upregulated in hemocytes. EsIRP knockdown resulted in increased expression of both EsFer-1 and EsFer-2. After EsFer-1 and EsFer-2 knockdown, the bacterial clearance ability of E. sinensis against S. aureus and V. parahaemolyticus was impaired. In conclusion, our results suggest that the IRP-IRE signaling pathway plays an important role in the innate immune system response in E. sinensis.

The aim of this study was to investigate the effect of miR-4778-3p on the radiosensitivity of cervical cancer cells and to elucidate the underlying mechanism. Tissue samples were collected from eight patients with cervical cancer prior to chemoradiotherapy. MicroRNA chip analyses, RT-PCR, gene transfection, CCK8, wound healing and Transwell assays, colony-forming assay, western blot, and the Dual-Luciferase Reporter Assay System were used to evaluate the role of miR-4778-3p in cervical cancer radiosensitivity and its relationships with target molecules NR2C2 and Med19. Thirty-two differentially expressed miRNA molecules (fold-change 2; p 0.05) associated with cervical cancer radioresistance were identified. The expression of miR-4778-3p was significantly lower in recurrent or metastatic patients than in control subjects. In vitro studies using radioresistant HeLa and SiHa cervical cancer cell lines showed that miR-4778-3p upregulation significantly inhibited cell proliferation, invasiveness, and migration after irradiation. There was also a significant increase in apoptosis and a significant decrease in the proportion of cells at the G2/M phase. Further, miR-4778-3p upregulation led to increased expression of apoptosis-related molecules, such as Bax, Caspase-3, Caspase-8, and Caspase-9. Reporter gene assays showed that miR-4778-3p bound specifically to NR2C2 and Med19 and negatively regulated their expression. Thus, miR-4778-3p reduces the vitality, proliferation, and migration of radioresistant cervical cancer cells and may regulate the radiosensitivity of cervical cancer by targeting and regulating NR2C2 and Med19 expression.

To observe the effect of electroacupuncture (EA) intervention on hyperplastic mammary glands, serum estradiol (ESixty female SD rats were randomly divided into control, model, EA, EA＋ovariectomy(OVX) and EA＋sham-OVX groups (The height of nipples, serum EEA intervention can improve hyperplastic mammary glands by down-regulating serum E

A sequencing batch reactor (SBR) with alternating anaerobic/oxic (An/O) operation was employed to investigate nitrogen and phosphorus removal performance and corresponding phosphate recovery effect of an enhanced biological phosphorus removal (EBPR) system when extracting side stream ratios of 0, 1/4, 1/3, 1/2 anaerobic phosphorus supernatant. The operation involved three runs within 310 days. Removal efficiencies of COD and NH

In this study, a sequencing batch reactor (SBR) was operated to investigate the inhibitory kinetics of free ammonia (FA) on ammonia-oxidizing bacteria (AOB). At the beginning of the experiment, FA concentrations in influent were altered to achieve stable short-cut nitrification and enrich AOB. Nitritation sludge was then employed to study variations in the specific nitrite production rate (SNiPR) during the ammonia oxidation process of batch tests. Furthermore, a kinetic model of FA inhibition on AOB activity was fitted for statistical analysis. Results showed that SNiPR increased rapidly with increase in FA concentration (0.7 mg·L

To investigate the correlation between the single nucleotide polymorphism (SNP) rs662 of the paraoxonase 1 gene (PON1) and the risk of male infertility.This case-control study included 403 male idiopathic infertility patients aged 29.00 ± 4.48 years in the case group and 329 normal fertile men aged 28.28 ± 4.08 years as healthy controls. We obtained DNA from the peripheral venous blood of the subjects, genotyped the SNP rs662 of PON1 by Sequenom MassArray, and analyzed the association between different genotypes of PON1 rs662 and male infertility using the logistic regression model.Compared with the normal controls, the infertility patients showed a significantly increased level of follicle-stimulating hormone (FSH) (［16.30 ± 17.76］ vs ［4.72 ± 2.51］ U/L, P0.01) but a decreased percentage of progressively motile sperm (PMS) (［7.40 ± 14.17］ % vs ［41.93 ± 9.06］ %, P0.01) and sperm concentration (［2.74 ± 3.64］ vs ［75.83 ± 63.66］ ×10⁶/ml, P0.01). Statistically significant differences were not found in the other parameters between the two groups of subjects, nor in the correlation of male infertility with the heterozygous genotype GA versus the wild homozygous genotype GG (OR = 0.98, 95% CI: 0.63－1.53, P = 0.923) or the homozygous genotype AA versus the wild homozygous genotype GG (OR = 0.87, 95% CI: 0.56－1.34, P = 0.525).The SNP rs662 of PON1 was not correlated with male infertility, which, however, needs to be confirmed by further studies with larger samples from a larger area.目的： 探讨对氧磷酶1（PON1）基因rs662(c.575AG)位点单核苷酸多态性与男性不育发病风险之间的相关性。方法： 采用病例-对照研究的方法，选取403例特发性男性不育患者作为病例组，329例正常生育的男性作为对照组。病例组年龄为(29.00 ± 4.48)岁，对照组年龄为(28.28± 4.08)岁。取外周静脉血，并用DNA试剂盒提取DNA，随后用Sequenom MassArray技术对PON1 rs662位点进行基因分型，分析PON1 rs662位点不同基因型与男性不育发病风险之间的相关性。 结果： 病例组与对照组相比，卵泡刺激素［ (16.30±17.76) U/L vs (4.72±2.51) U/L］、前向运动精子百分率［(7.40±14.17) % vs (41.93±9.06) %］、精子浓度［ (2.74±3.64) ×10⁶/ml vs (75.83±63.66) ×10⁶/ml］ 存在明显差异且具有统计学意义（P0.01），其他参数无统计学意义的差异。杂合突变型GA与野生型纯合GG相比较：OR=0.98，95%CI：0.63~1.53，P=0.923，纯合突变型AA与野生型纯合GG相比较：OR=0.87，95%CI：0.56~1.34，P=0.525。两组结果均显示PON1 rs662位点与男性不育发病风险之间无相关性，各亚组分析显示该基因多态性位点与男性不育发病风险之间不存在相关性。结论： PON1 rs662位点基因多态性与男性不育发病风险之间不存在相关性，但是由于实验样本条件的限制，需要更大的样本量以及样本选取范围进行进一步研究。

HLA-A*01:127 has one nucleotide change from HLA-A*01:25 where 158 Valine is changed to Alanine.

The Janus kinase/signal transducers and activators of transcription (JAK/STAT) signalling pathway plays a significant role in immune responses to pathogens. In invertebrates, three core components (Domeless, Hopscotch and STAT92E) of the JAK/STAT pathway were first identified in Drosophila melanogaster. In the present study, we report the cloning and characterisation of DOME, JAK and STAT from Eriocheir sinensis. EsDOME, EsJAK and EsSTAT are 1299, 1110 and 794 amino acid proteins encoded by 4200, 3333 and 2385 bp open reading frames, respectively. Bioinformatics analysis revealed that all three share specific domains with corresponding functions. Quantitative real-time PCR showed that all three components were highly expressed in various tissues including the gill, hepatopancreas and hemocytes. Moreover, EsDOME, EsJAK and EsSTAT were upregulated significantly in hemocytes after bacterial challenge. In addition, the JAK/STAT signalling pathway positively regulates antimicrobial peptide expression during the antibacterial immune response. Thus, the JAK/STAT pathway plays a critical role in bacterial immune responses in E. sinensis.

The ubiquitin-proteasome system is involved in numerous cellular processes, such as signal transduction, autophagy, cell cycle control, embryogenesis, and regulation of immune response. Neural precursor cell expressed developmentally downregulated 8 (NEDD8) is a ubiquitin-like protein that activates Cullin-RING ligases and modifies substrates via neddylation. However, there is limited information on how neddylation regulates innate immunity in crustaceans. In the present study, we identified the evolutionarily conserved NEDD8 with the ubiquitin homologue domain in the Chinese mitten crab (Eriocheir sinensis), named it EsNEDD8. Then, we analyzed the expression patterns and cellular location of its substrate, EsCullin4. qRT-PCR showed that both EsNEDD8 and EsCullin4 were widely expressed in all the selected tissues, and EsCullin4 was significantly upregulated in hemocytes after bacterial stimulation. Moreover, silencing of EsCullin4 significantly suppressed the expression of antimicrobial peptides (AMPs) in the hemocytes after bacterial stimulation, and inhibition of EsCullin4 neddylation by treatment with the NEDD8-activating enzyme inhibitor MLN4924 significantly inhibited the expression of the AMPs. Thus, the results show that EsNEDD8-modified EsCullin4 could control antimicrobial activities via regulation of AMPs expression in the Chinese mitten crab.

Alzheimer’s disease (AD), the most common type of dementia, is becoming a major challenge for global health and social care. However, the current understanding of AD pathogenesis is limited, and no early diagnosis and disease-modifying therapy are currently available. During the past year, significant progress has been made in clinical research on the diagnosis, prevention, and treatment of AD. In this review, we summarize the latest achievements, including diagnostic biomarkers, polygenic hazard score, amyloid and tau PET imaging, clinical trials targeting amyloid-beta (Aβ), tau, and neurotransmitters, early intervention, and primary prevention and systemic intervention approaches, and provide novel perspectives for further efforts to understand and cure the disease.

Previous studies suggest that gut microbiota is associated with neuropsychiatric disorders, such as Parkinson's disease, amyotrophic lateral sclerosis, and depression. However, whether the composition and diversity of gut microbiota is altered in patients with Alzheimer's disease (AD) remains largely unknown. In the present study, we collected fecal samples from 43 AD patients and 43 age- and gender-matched cognitively normal controls. 16S ribosomal RNA sequencing technique was used to analyze the microbiota composition in feces. The composition of gut microbiota was different between the two groups. Several bacteria taxa in AD patients were different from those in controls at taxonomic levels, such as Bacteroides, Actinobacteria, Ruminococcus, Lachnospiraceae, and Selenomonadales. Our findings suggest that gut microbiota is altered in AD patients and may be involved in the pathogenesis of AD.

The transcription factor SOX10, as a major actor in the development of the neural crest, plays a key role in the maintenance of progenitor cell multipotency, lineage specification, and cell differentiation. Abnormalities of neural crest development in humans lead to a number of genetic diseases known as neurocristopathies or neural crest disorders. The mutation of SOX10 can cause Kallmann syndrome (KS), which is a clinically and genetically heterogeneous condition and defined by the association between anosmia and hypogonadotropic hypogonadism due to incomplete migration of neuroendocrine gonadotropin-releasing hormone (GnRH) cells along the olfactory, vomeronasal, and terminal nerves. Since then, there have been a number of related reports that mutation of SOX10 will lead to KS with deafness. This review focuses on the SOX10 gene and the advances in the diagnosis and genetic studies of KS with deafness caused by the mutatuin of SOX10.SOX10是神经嵴发育中的关键转录因子，在维持祖细胞多能性、细胞系谱专向分化和神经嵴细胞的发育中发挥着重要作用。研究指出，SOX10基因突变使神经嵴细胞发育不良而导致相应细胞、组织发生病变，包括内分泌系统、周围神经系统、循环系统和骨骼肌系统，所导致的疾病统称为神经嵴病。同时，SOX10基因突变会导致合并耳聋的Kallmann综合征（KS），KS是一种先天性性腺功能低下和嗅觉减退或缺失联合的遗传病，是特发性低促性腺激素性性腺功能减退症（IHH）中常见的类型。因先天性下丘脑促性腺激素释放激素（GnRH）神经元的不完全迁移导致，具有临床和遗传异质性。本文就SOX10基因及其在合并耳聋的KS发病中作用的研究进展展开综述。.

To investigate the correlation of the single nucleotide polymorphism (SNP) rs1042522 of the tumor protein p53 (TP53) gene with the risk of male infertility.This casecontrol study included 380 male patients with idiopathic infertility and 398 normal fertile men as controls from the Nanjing area. We genotyped the SNP rs1042522 of the TP53 gene by Sequence Mass Array and analyzed the correlation of the SNP with male infertility using the logistic regression model.Compared with the normal controls, the patients with idiopathic infertility showed significantly decreased sperm concentration (［77.34±49.24］ vs ［13.13±24.96］ ×106/ml), percentage of progressively motile sperm (［42.55±9.57］ vs ［10.38±5.57］%), serum testosterone level (［14.07±5.36］ vs ［11.89±4.50］ nmol/L), and folliclestimulating hormone level (［16.80±18.20］ vs ［4.55±7.17］ U/L) (P0.05) but no statistically significant differences in other parameters. No correlation was observed between the SNP frequencies and male infertility and similar results were found in the subgroups of the cases.SNP rs1042522 of the TP53 gene is not significantly correlated with the risk of male infertility.目的： 探讨肿瘤蛋白p53(TP53)基因rs1042522位点单核苷酸多态性与男性不育的关系。方法： 采用病例对照研究，收集南京地区特发性男性不育患者380例（病例组）,有生育史的健康男性398例（对照组）；并将病例组分为无精子症组(n=140)和少精子症组(n=240)。用Sequence MassArray技术检测TP53基因rs1042522位点的基因型，通过Logistic回归分析该位点多态性与男性不育的相关性。 结果： 病例组与对照组前向运动精子百分率［(10.38 ± 5.57)% vs (42.55 ± 9.57)%］、精子浓度［(13.13 ± 24.96)×10⁶/mlvs (77.34 ± 49.24)×106/ml］、T［(14.07 ± 5.36) nmol/L vs (11.89 ± 4.50) nmol/L］、FSH［(16.80 ± 18.20) U/L vs (4.55 ± 7.17) U/L］存在显著性差异（P0.05）。经Logistic回归分析，未发现各基因型与男性不育有统计学意义的相关性，亚组分析也未发现相关性。 结论： TP53基因rs1042522位点的单核苷酸多态性与男性不育无显著相关性。.

To investigate the correlation of the single nucleotide polymorphism (SNP) rs4880 of the superoxide dismutase 2 (SOD2) gene with the risk of male infertility.This casecontrol study included 519 male patients with idiopathic infertility (aged 19－40 ［28.93±4.93］ years) in the case group and 338 fertile men (aged 19－40 ［28.40±4.25］ years) in the control group. We collected the clinical data, genotyped the SNP rs4880 of the SOD2 gene by Sequenom Mass Array, and analyzed the association of different genotypes with male infertility using the logistic regression model.Statically significant differences were observed between the case and control groups in the level of folliclestimulating hormone (FSH) (［4.72±2.51］ vs ［15.65±17.24］ U/L, P0.01), the percentage of progressively mobile sperm (［9.12±13.5］ vs ［41.95±9.03］%, P0.01), and sperm concentration (［12.95±24.38］ vs ［72.88±45.60］ ×106/ml, P0.01), but not in other parameters. No correlation was found between male infertility and the heterozygous genotype TC (OR = 0.90, 95% CI: 0.65－1.25, P = 0.516) or the homozygous genotype CC (OR=1.49, 95% CI: 0.38－5.81, P = 0.566) as compared with the wild genotype TT, and similar results were obtained in the analysis of the subgroups.The SNP rs4880 of the SOD2 gene was not correlated with male infertility, which, however, is to be supported by further studies with larger samples from more areas.目的： 探讨超氧化物歧化酶2（SOD2）基因rs4880位点单核苷酸多态性与男性不育发病风险的相关性。 方法： 采用病例对照研究的方法，选取519例特发性男性不育患者作为病例组，年龄19~40（28.92 ± 4.37）岁，并按精子浓度和前向运动（PR）精子百分率分为无精子症组（n=143）、严重少精子症组（n=175）、少精子症组（n=89）和弱精子症组（n=112）4个亚组；以338例正常生育的男性作为对照组，年龄19~40（28.40 ± 4.25）岁，进行临床数据的采集。用Sequenom MassArray技术对SOD2 rs4880位点进行基因分型，用Logistic回归模型分析SOD2 rs4880位点不同基因型与男性不育之间的关系。 结果： 病例组与正常对照组FSH、PR精子百分率、精子浓度存在显著差异（P0.01）。与野生型纯合TT比较，杂合突变型TC（OR=0.90，95%CI：0.65~1.25，P=0.516）与纯合突变型CC（OR=1.49，95%CI：0.38~5.81，P=0.566）均显示与男性不育无相关性；亚组分析中均显示该基因位点与男性不育不存在相关性：无精子症组中，TC/TT(OR=0.99.95%CI:0.62~1.58，P=0.967),CC/TT(OR=1.58,95%CI:0.26~9.59，P=0.619；严重少精子症组中，TC/TT(OR=1.07.95%CI:0.70~1.64，P=0.750),CC/TT(OR=1.31,95%CI:0.22~7.96，P=0.767；少精子症组中，TC/TT(OR=0.83.95%CI:0.47~1.48，P=0.535),CC/TT(OR=1.22,95%CI:0.13~11.90，P=0.865)；弱精子症组中，TC/TT(OR=0.59.95%CI:0.33~1.05，P=0.074),CC/TT(OR=1.84,95%CI:0.30~11.16，P=0.510)。结论： SOD2 rs4880位点基因多态性与男性不育不存在相关性，但是由于实验样本条件的限制，需要更大的样本量以及样本选取范围来进一步研究验证。.

The Down syndrome cell adhesion molecule (Dscam) gene is an extraordinary example of diversity that can produce thousands of isoforms and has so far been found only in insects and crustaceans. Cumulative evidence indicates that Dscam may contribute to the mechanistic foundations of specific immune responses in insects. However, the mechanism and functions of Dscam in relation to pathogens and immunity remain largely unknown. In this study, we identified the genome organization and alternative Dscam exons from Chinese mitten crab, Eriocheir sinensis. These variants, designated EsDscam, potentially produce 30,600 isoforms due to three alternatively spliced immunoglobulin (Ig) domains and a transmembrane domain. EsDscam was significantly upregulated after bacterial challenge at both mRNA and protein levels. Moreover, bacterial specific EsDscam isoforms were found to bind specifically with the original bacteria to facilitate efficient clearance. Furthermore, bacteria-specific binding of soluble EsDscam via the complete Ig1-Ig4 domain significantly enhanced elimination of the original bacteria via phagocytosis by hemocytes; this function was abolished by partial Ig1-Ig4 domain truncation. Further studies showed that knockdown of membrane-bound EsDscam inhibited the ability of EsDscam with the same extracellular region to promote bacterial phagocytosis. Immunocytochemistry indicated colocalization of the soluble and membrane-bound forms of EsDscam at the hemocyte surface. Far-Western and coimmunoprecipitation assays demonstrated homotypic interactions between EsDscam isoforms. This study provides insights into a mechanism by which soluble Dscam regulates hemocyte phagocytosis via bacteria-specific binding and specific interactions with membrane-bound Dscam as a phagocytic receptor.

Neonatal cholestatic disorders are a group of hepatobiliary diseases occurring in the first 3 months of life. The most common causes of neonatal cholestasis are infantile hepatitis syndrome (IHS) and biliary atresia (BA). The clinical manifestations of the two diseases are too similar to distinguish them. However, early detection is very important in improving the clinical outcome of BA. Currently, a liver biopsy is the only proven and effective method used to differentially diagnose these two similar diseases in the clinic. However, this method is invasive. Therefore, sensitive and non-invasive biomarkers are needed to effectively differentiate between BA and IHS. We hypothesized that urinary metabolomics can produce unique metabolite profiles for BA and IHS. The aim of this study was to characterize urinary metabolomic profiles in infants with BA and IHS, and to identify differences among infants with BA, IHS, and normal controls (NC). Urine samples along with patient characteristics were obtained from 25 BA, 38 IHS, and 38 NC infants. A non-targeted gas chromatography–mass spectrometry (GC–MS) metabolomics method was used in conjunction with orthogonal partial least squares discriminant analysis (OPLS-DA) to explore the metabolomic profiles of BA, IHS, and NC infants. In total, 41 differentially expressed metabolites between BA vs. NC, IHS vs. NC, and BA vs. IHS were identified. N-acetyl-d-mannosamine and alpha-aminoadipic acid were found to be highly accurate at distinguishing between BA and IHS. BA and IHS infants have specific urinary metabolomic profiles. The results of our study underscore the clinical potential of metabolomic profiling to uncover metabolic changes that could be used to discriminate BA from IHS.

CAG-repeat in the polymerase γ (POLG) gene encoding polymerase γ for mitochondria is important to spermatogenesis. Compared with a few researchers who raised alteration of CAG-repeat-affected male reproductive ability, others did not find the association between CAG-repeat polymorphisms and male infertility. Therefore, a comprehensive meta-analysis is necessary to determine the association; 13 case-control studies were screened out using keywords search. From these studies, characteristics were extracted for conducting meta-analysis. Odds ratio (OR) and 95% confidence interval (CI) were used to describe the results; the results indicated that CAG-repeat allele was not a risk factor to male infertility (pooled OR = 1.03, 95% CI: 0.79-1.34, P = 0.828). Four different genetic comparisons also demonstrated a negative result: heterozygote comparison (not 10/10 versus 10/10. Pooled OR = 0.99, 95% CI: 0.77-1.27, P = 0.948), homozygote comparison (not 10/not 10 versus 10/10. Pooled OR = 1.08, 95% CI: 0.56-2.06, P = 0.816), the recessive genetic comparison (not 10/not 10 versus not 10/10 + 10/10. Pooled OR = 1.07, 95% CI: 0.58-1.95, P = 0.829) and the dominant genetic comparison (not 10/not 10 + not 10/10 versus 10/10. Pooled OR = 0.97, 95% CI: 0.72-1.29, P = 0.804); based on current researches, this meta-analysis demonstrated no apparent association between POLG-CAG-repeat and male infertility. Similarly, CAG-repeat was not a sensitive site to male infertility.

How to provide effective prevention and treatment of myocardial ischemia/reperfusion (I/R) injury and study of the mechanism underlying I/R injury are hotspots of current research. This study aimed to elucidate the effect and cardioprotective mechanism of vitamin C (VC) on myocardial I/R injury. Our study introduced two different I/R models: I/R in vitro and oxygen-glucose deprivation/recovery (OGD/R) in primary neonatal rat cardiac myocytes. We used the mitochondrial permeability transition pore (mPTP) opener lonidamine (LND) and the mitochondrial KATP (mitoKATP) channel inhibitor 5-hydroxydecanoate (5-HD) to analyze the underlying mechanisms. We found that post-treatment with VC decreased I/R injury in our models. Post-treatment with VC significantly decreased I/R-induced injury, attenuated apoptosis, and maintained the functional integrity of mitochondria via alleviation of Ca(2+) overload, reactive oxygen species burst, inhibition of the opening of mPTP, and prevention of mitochondrial membrane potential (ΔΨm) depolarization. VC post-treatment increased the phosphorylation of Akt and glycogen synthase kinase (GSK)-3β. The present results demonstrate that VC might protect the myocardium from I/R-induced injury by inhibiting the mPTP opening via activation of mitoKATP channels. VC mediates cardioprotection via activation of the phosphatidyl inositol 3-kinase (PI3K)-Akt signaling pathway. These findings may contribute toward the development of novel strategies for clinical cardioprotection against I/R injury.

Topic model is a powerful tool for the basic document or image processing tasks. In this study we introduce a novel image topic model, called Latent Patch Model (LPM), which is a generative Bayesian model and assumes that the image and pixels are connected by a latent patch layer. Based on the LPM, we further propose an image denoising algorithm namely multiple estimate LPM (MELPM). Unlike other works, the proposed denoising framework is totally implemented on the latent patch layer, and it is effective for both Gaussian white noises and impulse noises. Experimental results demonstrate that LPM performs well in representing images. And its application in image denoising achieves competitive PSNR and visual quality with conventional algorithms.

To investigate the neuroprotective effects of icariin on formaldehyde (FA)-treated human neuroblastoma SH-SY5Y cells and the possible mechanisms involved. SH-SY5Y cells were divided into FA treatment group, FA treatment group with icariin, and the control group. Cell viability, apoptosis, and morphological changes were determined by cell counting kit-8 (CCK 8), flow cytometry, and confocal microscopy, respectively. The phosphorylation of Tau protein was examined by western blotting. FA showed a half lethal dose (LD50) of 0.3 mmol/L in SH-SY5Y cells under the experimental conditions. Icariin (1–10 µmol/L) prevented FA-induced cell death in SH-SY5Y cells in a dose-dependent manner, with the optimal effect observed at 5 µmol/L. After FA treatment, the absorbance in FA group was 1.31±0.05, while in the group of icariin (5 µmol/L) was 1.63±0.05. Examination of cell morphology by confocal microscopy demonstrated that 5 µmol/L icariin significantly attenuated FA-induced cell injury (P

In order to advance immunological research, a modified primary cell culture method for hemocytes from Eriocheir sinensis (Chinese mitten crab) was established using L-15 medium lacking FBS and CO 2 at 28 °C. Under these conditions, cultured cells were stably propagated for 30 days. To evaluate cellular activity, expression levels of certain critical immune-related genes, melanization of the hemocytes, and the phosphorylation status of key molecules in cell signaling pathways were analyzed. mRNA expression level of EsDWD1, EsLecG and EsToll2 was upregulated after LPS, PGN and GLU stimulation. Meanwhile, stimulated by Vibrio parahemolyticus led to the melanization of the hemocytes, and the melanization was more obviously with the increasing concentration of bacteria. Moreover, exposure to V. parahemolyticus significantly induced JNK, ERK and p38 phosphorylation, with the greatest extent of phosphorylation observed 30 min post-induction. Collectively, our results establish a technique for E. sinensis hemocyte primary culture and demonstrate appropriate immunological response, regulation and activity. Statement of relevance We declare that we have no conflict of interest statement.

The 46,XX male disorder of sex development (DSD) is rarely observed in humans. Patients with DSD are all male with testicular tissue differentiation. The mechanism of sex determination and differentiation remains to be elucidated. In the present case report, an 46,XX inv (9) infertile male negative for the sex-determining region of the Y chromosome (SRY) gene was examined. This infertile male was systemically assessed by semen analysis, serum hormone testing and gonadal biopsy. Formalin-fixed and paraffin-embedded gonad tissues were assessed histochemically. The SRY gene was analyzed by fluorescence in situ hybridization (FISH) and polymerase chain reaction (PCR). The other 23 specific loci, including the azoospermia factor region on the Y chromosome and the sequence-targeted sites of the SRY-box 9 (SOX9) gene were analyzed by PCR. The genes RSPO1, DAX1, SOX3, ROCK, DMRT1, SPRY2 and FGF9 were also assessed using sequencing analysis. Affymetrix Cytogenetics Whole Genome 2.7 M Arrays were used for detecting the genomic DNA from the patient and the parents. The patient with the 46,XX inv (9) (p11q13) karyotype exhibited male primary, however, not secondary sexual characteristics. However, the patient's mother with the 46, XX inv (9) karyotype was unaffected. The testicular tissue dysplasia of the patient was confirmed by tissue biopsy and absence of the SRY gene, and the other 23 loci on the Y chromosome were confirmed by FISH and/or PCR. The RSPO1, DAX1, SOX3, ROCK, DMRT1, SPRY2 and FGF9 genes were sequenced and no mutations were detected. A duplication on the 3 M site in the upstream region of SOX9 was identified in the patient as well as in the mother. The patient with the 46,XX testicular DSD and SRY-negative status was found to be infertile. The duplication on the 3 M site in the upstream region of SOX9 was a polymorphism, which indicated that the change was not a cause of 46,XX male SDS. These clinical, molecular and cytogenetic findings suggested that other unidentified genetic or environmental factors are significant in the regulation of SDS.

Herein, we report, for the first time, the synthesis of reduced graphene oxide–DNA–Ag (RGO–DNA–Ag) nanohybrids by ultraviolet (UV) irradiation of aqueous solutions of GO and Ag ions in the presence of DNA. The morphology and microstructure characterizations of the resultant nanohybrids reveal that the proposed method leads to the simultaneous reduction of GO and Ag ions together with efficient dispersion of Ag nanoparticles on the surface of RGO sheets. This simple and fast synthesis route is carried out at ambient conditions without using any additional chemical reducing agents, which has the potential to provide new avenues for the green fabrication of various RGO-based nanomaterials. Additionally, the RGO–DNA–Ag nanohybrids can be utilized as a novel sensing interfacial for direct determination of iodide by simple differential pulse voltammetry (DPV), without requiring any preceding preconcentration of the analyte. Based on the RGO–DNA–Ag nanohybrids modified electrode, a wide linear range of 1 μM–1 mM and a low detection limit of 0.2 μM were obtained. This sensitive and direct method of analysis can be applied successfully to the determination of iodide in real samples.

By analyzing two Polycarboxylate cement admixture of different polymerization process adaptability, the cement paste experiment is carried out to show the influence of Polycarboxylate superplasticizer, slump agent and the cement synthesis process on cement adaptability. Through orthogonal design method, result is drawn from the comparison of the influence of initial liquidity and an hour liquidity under different conditions,which is base on treating Polymeric acid process parameters as effecting factor within a certain range. It is shown that the preferably optimized process parameters of Polycarboxylic acid exist in the same kind of cement.The system error caused by the impact of cement composition is indicated in different kinds of cement.The adaptability of Polycarboxylic acid cement admixture of the mother liquor is available in the process optimization of the parameters.

A very simple and effective approach of fabricating Au-reduced graphene oxide (Au-RGO) nanocomposite is herein reported. The nanocomposite was synthesized through a one-pot in situ reduction of graphene oxide (GO) and HAuCl4 under ultraviolet (UV) irradiation without using any additional chemical reducing agents, capping agents, stabilizer or surfactant. The surface characterization with various techniques such as UV–vis spectroscopy, Fourier transform infrared spectroscopy, Raman spectroscopy and transmission electron microscopy (TEM) showed that GO was effectively reduced and Au nanoparticles with a uniform size were well dispersed on the surface of RGO. This UV light assisted synthesis of Au-RGO nanocomposite is expected to be a universal and clean approach for the formation of various RGO-based nanocomposites. Significantly, the as-prepared nanocomposite possessed high activity in the redox behavior of As (III). Based on the Au-RGO nanocomposite modified electrode, a simple, sensitivity and selective sensing platform for the detection of As (III) was developed. Under optimum conditions, a detection range of 0.3–20 ppb and a low detection limit of 0.1 ppb were obtained, which is found to be well below the World Health Organization (WHO) guidelines of 10 ppb.

Severe traumatic brain injury (TBI) elicits destruction of both gray and white matter, which is exacerbated by secondary proinflammatory responses. Although white matter injury (WMI) is strongly correlated with poor neurological status, the maintenance of white matter integrity is poorly understood, and no current therapies protect both gray and white matter. One candidate approach that may fulfill this role is inhibition of class I/II histone deacetylases (HDACs). Here we demonstrate that the HDAC inhibitor Scriptaid protects white matter up to 35 d after TBI, as shown by reductions in abnormally dephosphorylated neurofilament protein, increases in myelin basic protein, anatomic preservation of myelinated axons, and improved nerve conduction. Furthermore, Scriptaid shifted microglia/macrophage polarization toward the protective M2 phenotype and mitigated inflammation. In primary cocultures of microglia and oligodendrocytes, Scriptaid increased expression of microglial glycogen synthase kinase 3 beta (GSK3β), which phosphorylated and inactivated phosphatase and tensin homologue (PTEN), thereby enhancing phosphatidylinositide 3-kinases (PI3K)/Akt signaling and polarizing microglia toward M2. The increase in GSK3β in microglia and their phenotypic switch to M2 was associated with increased preservation of neighboring oligodendrocytes. These findings are consistent with recent findings that microglial phenotypic switching modulates white matter repair and axonal remyelination and highlight a previously unexplored role for HDAC activity in this process. Furthermore, the functions of GSK3β may be more subtle than previously thought, in that GSK3β can modulate microglial functions via the PTEN/PI3K/Akt signaling pathway and preserve white matter homeostasis. Thus, inhibition of HDACs in microglia is a potential future therapy in TBI and other neurological conditions with white matter destruction.

The oscillating hydrofoil current generation device utilizes a typical movement type, which can transform energy effectively from current. The study shows that the geometrical profile of blades is the fundamental factor to the efficiency. In order to resolve the problem, this paper adapt the BEM(blade elements momentum) theory, which plays an important role in resolving the turbine blade design. Use the MATLAB to calculate of the constraint equations, then translate the coordinates which has got through the calculation to Solidworks which is a convenient 3D modeling soft. In the end we will give an example which has modeled 3-D hydrofoil BEM theory.

Dyschromatosis symmetrica hereditaria (DSH) is a rare autosomal dominant pigmentary genodermatosis, which is characterized by a mixture of hyperpigmented and hypopigmented macules on the dorsal of the hands and feet, and on the face presented like freckle. Identification of RNA-specific adenosine deaminase 1 (ADAR1) gene results in DSH. This study was mainly to explore the pathogenic mutation of ADAR1 gene and provide genetics counselling and prenatal diagnostic testing for childbearing individuals.Mutational analysis of ADAR1 gene was performed by polymerase chain reaction (PCR) and electrophoretic separation of PCR products by 1.5% agarose gel electrophoresis. The coding exons and intron/exon flanking regions followed by bidirectional sequencing was performed on all participants. In this study, we found that a 28 year-old male patient harbouring a deleterious substitution of Leu1052Pro in the ADAR1 gene in a typical DSH family. His mother suffered from the DSH also owns the same mutation. This mutation, however, is not identified in the unaffected members in this family and those 200 normal controls. In summary, this new mutation Leu1052Pro reported here is pathogenic and detrimental for DSH. Our finding not only enriches mutation database and contributes to dissecting further the correlation between mutation position and phenotypical features of DSH, but also provides genetics counselling and prenatal diagnostic testing for childbearing couple.

Purpose. Recent study shows that blood-derived amyloid-beta (Aβ) can induce cerebral amyloidosis and is involved in the pathogenesis of Alzheimer’s disease (AD). The vast majority of blood Aβ is generated from platelet. Whether blood Aβ levels are associated with the count of platelets remains unknown. Methods. 58 clinically diagnosed AD patients, 18 11C-PIB-PET diagnosed AD patients, and 61 age- and gender-matched cognitively normal controls were included to analyze the correlation of plasma Aβ levels with platelet count. 13 AD patients and 40 controls with cerebrospinal fluid (CSF) samples were included to further analyze the correlation of CSF Aβ levels with platelet count. Aβ40 and Aβ42 levels in plasma and CSF were measured by ELISA kits. Results. The plasma Aβ42 level was positively correlated with platelet count in both AD patients and control group, especially in AD patients with positive PIB-PET, while there was no correlation as to Aβ40. The CSF Aβ levels also had no significant correlation with platelet count. Conclusion. It suggests that platelets may be involved in the pathogenesis of AD and become a potential peripheral biomarker for AD.

To investigate the value of serum inhibin B (InhB) in predicting the results of testicular sperm extraction (TESE) in patients with azoospermia.This study included 191 cases of obstructive azoospermia (OA), 360 cases of nonobstructive azoospermia (NOA), and 100 male controls with normal semen parameters. According to whether sperm was found in TESE, the NOA patients were divided into a sperm-absence group (TESE－, n=127) and a sperm-presence group (TESE+, n=233). Blood samples were collected from the subjects between 8:00 and 10:00 am for measurement of the levels of serum InhB. The specificity and sensitivity of serum InhB predicting TESE outcome were analyzed with receiver operating characteristics curve (ROC).The serum InhB level was significantly lower in the TESE－ group (［19.7±34.8］ pg/ml) than in the OA (［106.8±66.2］ pg/ml), TESE+ (［98.2±62.4］ pg/ml) and normal control group (［108.3±65.0］ pg/ml) (P0.01), but there were no statistically significant differences among the latter three groups (P0.05). Analysis of ROC showed that the best cut-off value of serum InhB was 19.1 pg/ml. Under the cut-off value, AUCROC was 0.88, specificity 84.2%, sensitivity 90.1%, and accuracy 88.1%.The serum InhB level is a good and non-invasively obtained index of spermatogenesis and should be measured for predicting the results of TESE.目的： 探讨血清抑制素 B（INHB）检测在无精子症患者经睾丸抽吸术（TESE）结局预评估中的意义。 方法： 根据研究需要将受试者分为3组：梗阻性无精子症（OA）组（n=191)，非梗阻性无精子症（NOA）组（n=360）,精液参数正常对照组（n=100）。NOA组根据TESE结局分为TESE无精子组(TESE－,n=127)和TESE有精子组(TESE+,n=233)。血液标本均于上午8:00~10:00收集，测定其INHB值。 采用受试者工作特征曲线(ROC)分析评价血清INHB预测TESE结局的敏感性和特异性。 结果： TESE－组的血清INHB水平［(19.7±34.8) pg/ml］显著低于OA组［(106.8±66.2) pg/ml］、TESE+组［(98.2±62.4) pg/ml］及精液参数正常对照组［(108.3±65.0) pg/ml］（P0.01)，TESE+组的血清INHB水平与OA组、精液参数正常对照组无显著性差异（P0.05)。ROC曲线分析显示，血清INHB最佳分割点为19.1 pg/ml，此时ROC曲线下面积(AUCROC)为0.88，敏感性为90.1%，特异性为84.2%，诊断准确性达88.1%。结论： 血清INHB是一种良好的非侵入性的精子生成预测指标，无精子症患者TESE前应该常规行血清INHB检测以评估其TESE结局。.

Human cytomegalovirus (HCMV) infection in infants is a global problem and the liver is a target organ of HCMV invasion. However, the mechanism by which HCMV causes different types of liver injury is unclear, and there are many difficulties in the differential diagnosis of HCMV infantile cholestatic hepatopathy (ICH) and extrahepatic biliary atresia (EHBA). We established a non-targeted gas chromatography-mass spectrometry metabolomics method in conjunction with orthogonal partial least squares-discriminate analysis based on 127 plasma samples from healthy controls, and patients with HCMV infantile hepatitis, HCMV ICH, and HCMV EHBA to explore the metabolite profile of different types of HCMV-induced liver injury. Twenty-nine metabolites related to multiple amino acid metabolism disorder, nitrogen metabolism and energy metabolism were identified. Carbamic acid, glutamate, L-aspartic acid, L-homoserine, and noradrenaline for HCMV ICH vs. HCMV EHBA were screened as potential biomarkers and showed excellent discriminant performance. These results not only revealed the potential pathogenesis of HCMV-induced liver injury, but also provided a feasible diagnostic tool for distinguishing EHBA from ICH.

Congenital cataract, a leading cause of visual impairment, is characterized by opacities of the lens, and in most cases occurred at birth or shortly after. Epidemiologic studies on theprevalence of...