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Radiotherapy is the primary treatment for nasopharyngeal carcinoma while radioresistance can hinder efficient treatment. To explore the role of annexin A1 and its potential mechanisms in radioresistance of nasopharyngeal carcinoma, human nasopharyngeal carcinoma cell line CNE2-sh annexin A1 (knockdown of annexin A1) and the control cell line CNE2-pLKO.1 were constituted and CNE2-sh annexin A1 xenograft mouse model was generated. The effect of annexin A1 knockdown on the growth of xenograft tumor after irradiation and radiation-induced DNA damage and repair was analyzed. The results of immunohistochemistry assays and Western blotting showed that the level of annexin A1 was significantly downregulated in the radioresistant nasopharyngeal carcinoma tissues or cell line compared to the radiosensitive nasopharyngeal carcinoma tissues or cell line. Knockdown of annexin A1 significantly promoted CNE2-sh annexin A1 xenograft tumor growth compared to the control groups after irradiation. Moreover, the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assays revealed that knockdown of annexin A1 significantly inhibited apoptosis in vivo compared to the control groups. We assessed the intracellular reactive oxygen species levels and the extent of radiation-induced DNA damage and repair using reactive oxygen species assay, comet assays, and immunohistochemistry assay. The results showed that knockdown of annexin A1 remarkedly reduced the intracellular reactive oxygen species levels, level of DNA double-strand breaks, and the phosphorylation level of H2AX and increased the accumulation of DNA-dependent protein kinase in nasopharyngeal carcinoma cells after irradiation. The findings suggest that knockdown of annexin A1 inhibits DNA damage via decreasing the generation of intracellular reactive oxygen species and the formation of γ-H2AX and promotes DNA repair via increasing DNA-dependent protein kinase activity and therefore improves the radioresistance in nasopharyngeal carcinoma cells. Together, our findings suggest that knockdown of annexin A1 promotes radioresistance in nasopharyngeal carcinoma and provides insights into therapeutic targets for nasopharyngeal carcinoma radiotherapy.

Objective: To investigate the presence of colistin resistance gene mcr in gut bacteria from patients with acute diarrhea. Methods: Fresh stool samples were collected from 150 outpatients with acute diarrhea in the intestinal clinic of Henan Provincial People's Hospital, and were directly detected for the presence of mcr by PCR after enrichment in the broth.The mcr-producing bacteria were further isolated and identified by MALDI-TOF MS (Bruker Biotyper). Antimicrobial susceptibility of these isolates was conducted by micro-broth dilution method.The presence of other antimicrobial genes were investigated by PCR and sequencing. Results: Among the 150 cases of acute diarrhea, 4 patients(2.7%) were positive for mcr-1 gene, and only 1(0.7%) contained both mcr-1 and mcr-3.Four isolates of Escherichia coli and one isolate of Aeromonas veronii were obtained from the mcr positive cases.The presence of mcr-1 gene was found in all of the E . coli isolates, and the mcr-3 gene was identified in A . veronii . Conclusions: Our study demonstrated the relatively low prevalence of colistin resistant gene in the faeces of acute diarrhea outpatients, and mcr-1 is the dominant colistin resistant gene.The presence of mcr-3 gene was also found in the clinical sample, and it indicats the coexistence of mcr-1 and mcr-3 in the intestinal tract of diarrhea patient.We should pay attention to the potential transmission of these resistance genes and further investigations are urgently needed.

Antipsychotic agents have been reported to promote hippocampal neurogenesis and improve cognitive deficits; yet, the molecular mechanisms underlying these actions remain unclear. In the present study, we used a murine model of schizophrenia induced by 5-day intraperitoneal injection with the non-competitive N-methyl-d-aspartate receptor antagonist MK801 (0.3mg/kg/day) to assess cognitive behavioral deficits, changes in Notch signaling, and cellular proliferation in the hippocampus of adult male C57BL/6 mice after 2-week administration of risperidone (Rip, 0.2mg/kg/day) or vehicle. We then utilized in vivo stereotaxic injections of a lentivirus expressing a short hairpin RNA (shRNA) for Notch1 into the dentate gyrus to examine the role of Notch1 in the observed actions of Rip. We found that Rip ameliorated cognitive deficits and restored cell proliferation in MK801-treated mice in a manner associated with the up-regulation of Notch signaling molecules, including Notch1, Hes1, and Hes5. Moreover, these effects were abolished by pretreatment with Notch1 shRNA. Our results suggest that the ability of Rip to improve cognitive function in schizophrenia is mediated in part by Notch signaling., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Enamelin (ENAM) has three putative phosphoserines (pSers) phosphorylated by a Golgi-associated secretory pathway kinase (FAM20C) based on their distinctive Ser-x-Glu (S-x-E) motifs. Fam20C-knockout mice show severe enamel defects similar to those in the Enam-knockout mice, implying an important role of the pSers in ENAM. To determine the role of pSer 55 in ENAM, we characterized ENAM Rgsc514 mice, in which Ser 55 cannot be phosphorylated by FAM20C due to an E 57 >G 57 mutation in the S-x-E motif. The enamel microstructure of 4-week-old mice was examined by scanning electron microscopy. The teeth of 6-day-old mice were characterized by histology and immunohistochemistry. The protein lysates of the first lower molars of 4-day-old mice were analyzed by Western immunoblotting using antibodies against ENAM, ameloblastin and amelogenin. ENAM Rgsc514 heterozygotes showed a disorganized enamel microstructure, while the homozygotes had no enamel on the dentin surface. The N-terminal fragments of ENAM in the heterozygotes were detained in the ameloblasts and localized in the mineralization front of enamel matrix, while those in the WT mice were secreted out of ameloblasts and distributed evenly in the outer 1/2 of enamel matrix. Surprisingly, the ~15  kDa C-terminal fragments of ameloblastin were not detected in the molar lysates of the homozygotes. These results suggest that the phosphorylation of Ser 55 may be an essential posttranslational modification of ENAM and is required for the interaction with other enamel matrix molecules such as ameloblastin in mediating the structural organization of enamel matrix and protein-mineral interactions during enamel formation.International Journal of Oral Science (2017) 9;e4; doi:10.1038/ijos.2017.41; published online 29 November 2017.

Objective: To analyze the influence of growing experience on non-heterosexual orientation among male college students. Methods: From October to November in 2015, a total of 2 535 male students from 96 classes in 14 colleges/departments were recruited from two colleges that participated in the experimental work of AIDS prevention by cluster random sampling method. A structured questionnaire was administered in this study, including general demographic information, growing experience and Kinsey scale (to evaluate sexual orientation). Out of 2 500 questionnaires distributed in this study, 2 332 effective copies were withdrew, with the effective rate at 93.3%. Chi square test was used to analyze the differences of non-heterosexual orientation among the individuals with different social demographic characteristics. Multivariate logistic regression model was used to analyze the influencing factors of non-heterosexual orientation. Results: Among the 2 332 individuals, the proportion of self-reported non-heterosexual was 6.2% (144).The proportions of male students who identify as non-heterosexual from freshman to junior year were 5.2%(63/1216),6.9%(65/941),11.7%(13/111) and 4.7%(3/64), respectively (χ(2)=9.06, P= 0.029). Compared with the individuals of very good relationship with parents, those with bad relationship ( OR= 3.3, 95 %CI: 1.7-6.5) and general relationship ( OR= 1.7, 95 %CI: 1.0-2.9) with parents had a higher risk of non-heterosexual orientation, respectively. Those encountered sexual assault had a higher risk of non-heterosexual orientation than those without encountered sexual assault ( OR= 5.9, 95 %CI: 3.2-10.9). Conclusions: This study reported a high proportion of self-reported non-heterosexual among college male students in Nanjing, and highlighted the importance of targeting students with poor parental relationships and who subjected to sexually abused.

A main biochemical property of cancer cells, compared with normal cells, is altered redox status including increased levels of copper to maintain their malignant phenotypes. Thus, increasing copper accumulation, by using ionophores, to disrupt abnormal redox homeostasis of cancer cells may be an important anticancer strategy. Naturally occurring molecules with extraordinarily diverse chemical scaffolds are an important source of inspiration for developing copper ionophores. Dietary flavonoids are well-characterized copper chelators and show cancer chemopreventive potential, but their ionophoric role for redox-active copper and the related biological implications have remained unknown. This study reports, for the first time, the structural basis, chemical driving forces and biological implications of flavones (a widely distributed subgroup of flavonoids) as Cu(II) ionophores, and also provides new insights into cancer chemopreventive mechanism of flavones bearing 3(or 5)-hydroxy-4-keto group. 3-Hydroxyflavone surfaced as a potent Cu(II) ionophore to induce the mitochondria-dependent apoptosis of cancer cells in a redox intervention fashion via sequential proton-loss Cu(II) chelation, GSH-driving releasing of copper and protonation-dependent efflux of the neutral ligand., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The present study was designed to investigate the chemical constituents of the roots of Cyathula officinalis. Compounds were isolated by silica gel, Sephadex LH-20, ODS column chromatography, and preparative HPLC. Their structures were determined on the basis of 1D and 2D NMR techniques, mass spectrometry, and chemical methods. One new oleanane-type triterpenoid saponin, 28-O-[α-L-rhamnopyranosyl-(1→3)-β-D-glucuronopyranosyl-(1→3)-β-D-glucopyranosyl] hederagenin (1), was isolated from the roots of Cyathula officinalis. The anti-inflammatory activities of the isolates were evaluated for their inhibitory effects against LPS-induced nitric oxide (NO) production in RAW 264.7 macrophages cells. Compounds 2, 4, and 6 exhibited moderate anti-inflammatory activities., (Copyright © 2017 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

The awareness of facial expressions allows one to better understand, predict, and regulate his/her states to adapt to different social situations. The present research investigated individuals' awareness of their own facial expressions and the influence of the duration and intensity of expressions in two self-reference modalities, a real-time condition and a video-review condition. The participants were instructed to respond as soon as they became aware of any facial movements. The results revealed that awareness rates were 57.79% in the real-time condition and 75.92% in the video-review condition. The awareness rate was influenced by the intensity and (or) the duration. The intensity thresholds for individuals to become aware of their own facial expressions were calculated using logistic regression models. The results of Generalized Estimating Equations (GEE) revealed that video-review awareness was a significant predictor of real-time awareness. These findings extend understandings of human facial expression self-awareness in two modalities.

Objective: To identify the functions of the proteins containing the GGDEF or EAL domain in Lactobacillus acidophilus for investigation of the regulatory mechanism of c-di-GMP in this strain., Methods: The DNA fragments of NH13_07045-GGDEF, NH13_07050 and NH13_07055 from Lactobacillus acidophilus ATCC4356 were amplified by PCR and cloned into the expression vector pMAL-His-c2. After sequencing, the recombinant plasmids were transformed into competent Escherichia coli cells, which were induced by IPTG to express the recombinant proteins fused with maltose binding protein (MBP). The fusion proteins were purified using amylose resin column for diguanylate cyclase (DGC) or phosphodiesterase (PDE) activity assays in vitro followed by analysis with high-performance liquid chromatography (HPLC)., Results: The target DNA fragments were obtained by PCR, and their sequences were all identical to that in GenBank. The purified and concentrated fusion proteins, which were identified by SDS-PAGE and Western blotting, had relative molecular masses of 59 kD, 67 kD and 72 kD. HPLC analysis showed no DGC activity in NH13_07045-GGDEF, while PDE activity was found in NH13_07050 but not in NH13_07055., Conclusion: We obtained the protein encoded by NH13_07050 that possesses PDE activity in vitro. This protein may facilitate the evaluation of the regulatory function of c-di-GMP in Lactobacillus acidophilus.

Objective: The objective of the present study was to observe the relation between blood pressure variability (BPV) and early renal damage in hypertensive patients., Patients and Methods: A total of 118 hypertensive patients were consecutively selected. General parameters including sex, age, duration, and grade of hypertension, antihypertensive drugs taken, smoking status, blood sugar, blood lipid level, body mass index, indexes of 24-h ambulatory blood pressure monitoring and renal function including cystatin C (CysC), serum creatinine (SCr), angiotensin II (Ang II), microalbuminuria (mALb), and urine creatinine (UCr) were measured. Glomerular filtration rate (eGFR), endogenous creatinine clearance rate (Ccr), and urine albumin/creatinine ratio (UACR) were calculated by CysC level, SCr level, and mALb and UCr level respectively. The 24-h ambulatory blood pressure monitoring indexes included 24-h mean systolic blood pressure variability (24h-SBPV), 24-h mean diastolic blood pressure variability (24h-DBPV), day mean systolic blood pressure variability (d-SBPV), day mean diastolic blood pressure variability (d-DBPV), night mean systolic blood pressure variability (n-SBPV), and night mean diastolic blood pressure variability (n-DBPV)., Results: Sixty-four hypertensive patients (54.24%) were non-dipper, and the baseline data of the two groups were comparable. The 24h-SBPV, 24h-DBPV, d-DBPV, n-SBPV and SCr, eGFR, and Ccr of the two groups showed no significant differences. The d-SBPV, n-DBPV, CysC, and Ang II of the non-dipper group were significantly higher than those of the dipper group (p<0.05). The mALb in both groups increased and was more obvious in the non-dipper group. UACR of the non-dipper group was significantly higher than that of dipper group (p<0.05), while UCr showed no difference. By Pearson correlation, d-SBPV and n-DBPV correlated positively (p<0.05) with CysC, Ang II, mALb, and UACR., Conclusions: BPV of hypersensitive patients, especially the d-SBPV and n-DBPV, was closely related to indexes of early renal damage including CysC, Ang II, mALb, and UACR.

B-cell CLL/lymphoma 9 protein (BCL-9), a multi-functional co-factor in Wnt signaling, induced carcinogenesis as well as promoting tumor progression, metastasis and chemo-resistance in colorectal cancer (CRC). However, the mechanisms for increased BCL-9 expression in CRC were not well understood. Here, we report that hypoxia, a hallmark of solid tumors, induced BCL-9 mRNA expression in human CRC cells. Analysis of BCL-9 promoter revealed two functional hypoxia-responsive elements (HRE-B and HRE-C) that can be specifically bound with and be transactivated by hypoxia inducible factors (HIF) -1α but not HIF-2α. Consistently, ectopic expression of HIF-1α but not HIF-2α transcriptionally induced BCL-9 expression levels in cells. Knockdown of endogenous HIF-1α but not HIF-2α by siRNA largely abolished the induction of HIF by hypoxia. Furthermore, there was a strong association of HIF-1α expression with BCL-9 expression in human CRC specimens. In summary, results from this study demonstrated that hypoxia induced BCL-9 expression in human CRC cells mainly through HIF-1α, which could be an important underlying mechanism for increased BCL-9 expression in CRC.

With the development of urbanization, the effect of urban heat island has become increasingly evident. As an essential component of the urban natural landscapes, urban green space plays an important role in mitigating the effect of urban heat island. However, facing the rapid urbanization and changing environment, how to rationally plan and design the green space and realize its best cooling effect which can improve the urban environment and microclimate is still an urgent problem to be solved. So there is a strong need for mulitiscale researches on the cooling effect of urban green space. This paper systematically gave a review on the cooling effect of urban green space based on field measurement of air temperature, the main factors that influenced the cooling effect of green space were explored from three aspects including the area and shape characteristics of urban green space, the structure characteristics of vegetation and the external factors which affected the cooling effect, and the characteristics of the cooling effect of the green space were summarized from the aspect of time variation and distance decay. Then, the main problems and future research prospects of urban green space cooling effect were put forward.

Angiotensin-converting enzyme 2 (ACE2) is considered a potential therapeutic target of the renin-angiotensin system (RAS) for the treatment of cardiovascular diseases. We aimed to explore the effects of ACE2 overexpression on doxorubicin-induced cardiomyopathy in rats. Rats were randomly divided into treatment and control groups. The rats of treatment group were injected intraperitoneally with 6 doses of doxorubicin (2.5 mg/kg) within a period of two weeks. Two weeks after the initial injection of doxorubicin, these rats were randomly divided into Mock, Ad-EGFP, Ad-ACE2, and Cilazapril groups. The rats of Ad-EGFP and Ad-ACE2 groups received intramyocardial injection of Ad-EGFP and Ad-ACE2, respectively. The rats of Cilazapril group received cilazapril (10 mg/kg/day) via intragastric intubation. Apoptosis, inflammation, oxidative stress, cardiac function, the extent of myocardial fibrosis, and levels of ACE2, ACE, angiotensin II (AngII), and angiotensin (1-7) were evaluated. Four weeks after ACE2 gene transfer, the Ad-ACE2 group showed not only reduced apoptosis, inflammatory response, oxidative stress, left ventricular (LV) volume, extent of myocardial fibrosis and mortality of rats, but also increased LV ejection fraction and ACE2 expression level compared with the Mock and Ad-EGFP groups. ACE2 overexpression was superior to cilazapril in improving doxorubicin-induced cardiomyopathy. The putative mechanisms may involve activation of the AMPK and PI3K-AKT pathways, inhibition of the ERK pathway, decrease of TGF-β1 expression, and interactions of shifting RAS components, such as decreased myocardium AngII levels, increased myocardium Ang (1-7) levels, and reduced ACE expression. Thus, ACE2 may be a novel therapeutic approach to prevent and treat doxorubicin-induced cardiomyopathy.

Glycolysis is a typical conduit for energy metabolism in pancreatic cancer (PC) due to the hypoxic microenviroment. Lactate dehydrogenase A (LDHA) catalyzes the conversion of pyruvate to lactate and is considered to be a key checkpoint of anaerobic glycolysis. The aim of the present study was to explore the mechanism of interactions between hypoxia, HIF-1/2α and LDHA, and the function of LDHA on PC cells by analyzing 244 PC and paratumor specimens. It was found that LDHA was over-expressed and related to tumor stages. The result of in vitro study demonstrated that hypoxia induced LDHA expression. To explore the relationship between HIF and LDHA, chromatin immunoprecipitation assay and luciferase assay were performed. The result showed that HIF-1/2α bound to LDHA at 89bp under the hypoxic condition. Furthermore, knockdown of endogenous HIF-1α and HIF-2α decreased the LDHA expression even in the hypoxic condition, which was accompanied with a significant decrease in lactate production and glucose utilization (p < 0.01). Immunofluorescence in the 244 specimens showed that HIF-1/2α was over-expressed and associated with LDHA over-expression (p < 0.0001). Forced expression of LDHA promoted the growth and migration of PC cells, while knocking down the expression of LDHA inhibited the cell growth and migration markedly. In summary, the present study proved that HIF1/2α could activate LDHA expression in human PC cells, and high expression of LDHA promoted the growth and migration of PC cells.

Autophagy is an evolutionarily conserved process that plays a crucial role in maintaining a series of cellular functions. It has been found that autophagy is closely involved in the physiological process of spermatogenesis and the regulation of sperm survival and motility. However, the role of autophagy in high-fat diet (HFD)-induced impaired spermatogenesis remains unknown. This study was designed to investigate the role of autophagy in HFD-induced spermatogenesis deficiency and employed chloroquine (CQ) to inhibit autophagy and rapamycin (RAP) to induce autophagy. 3-methyladenine (3-MA) and CQ were administered via intratesticular injection in vivo. The effects of CQ and 3-MA on the parameters of spermatozoa co-cultured with palmitic acid (PA) in vitro were also investigated. Human semen samples from obese, subfertile male patients were also collected to examine the level of autophagy. The results suggested that HFD mice subjected to CQ showed improved spermatogenesis. Inhibiting autophagy with CQ improved the decreased fertility of HFD male mice. Moreover, the in vivo and in vitro results indicated that both CQ and 3-MA could suppress the pathological changes in spermatozoa caused by HFD or PA treatment. Additionally, the excessive activation of autophagy was also observed in sperm samples from obese, subfertile male patients.

Aim: To compare of lens oxidative damage induced by vitrectomy and/or hyperoxia in rabbit., Methods: Sixteen New Zealand rabbits (2.4-2.5 kg) were randomly divided into two groups (Group A, n =12; Group B, n =4). In Group A, the right eyes were treated with vitrectomy and systemic hyperoxia (oxygen concentration: 80%-85%, 1 ATA, 4h/d) (Group A-right), and the left eyes were treated with hyperoxia without vitrectomy surgery (Group A-left). Four rabbits in group B (eight eyes) were untreated as the controls. Lens transparency was monitored with a slit lamp and recorded before and after vitrectomy. After hyperoxic treatment for 6mo, the eyeballs were removed and the lens cortices (containing the capsules) and nuclei were separated for further morphological and biochemical evaluation., Results: Six months after treatments, there were no significant morphological changes in the lenses in any experimental group when observed with a slit lamp. However, the levels of water-soluble proteins and ascorbate, and the activities of catalase and Na + -K + -ATPase were significantly reduced, whereas the levels of malondialdehyde and transforming growth factor β2 (TGF-β2) were significantly elevated, in both the cortices and nuclei of eyes treated with vitrectomy and hyperoxia. The increase in protein-glutathione mixed disulfides and the reduction in water-soluble proteins were more obvious in the lens nuclei. The levels of ascorbate in the vitreous fluid were also reduced after vitrectomy, whereas TGF-β2 increased after vitrectomy and hyperoxia. Systemic hyperoxia exposure increased these effects., Conclusion: Removal of the intact vitreous gel with vitrectomy and exposing the lens to increased oxygen from the retina induce lens oxidation and aggregation. Thus, an intact vitreous gel structure may protect the lens from oxidative insult and maintain lens transparency.

Objective: Plasma adiponectin (APN) levels are decreased in diabetic patients. Dysfunctional mitochondrial biogenesis is involved in type 2 diabetes (T2DM) pathogenesis, by unclear mechanisms. The present study determined (1) whether myocardial mitochondrial biogenesis was impaired in cardiomyocytes exposed to a high glucose/high fat (HGHF) medium (a T2DM in vitro model), (2) the effects of APN administration upon mitochondrial biogenesis in cardiomyocytes affected by HGHF incubation, and 3) the involved underlying mechanisms., Materials and Methods: Neonatal rat ventricular myocytes (NRVMs) were isolated and incubated in HGHF medium. Mitochondrial function was assessed by ATP content, and fluorescent microscopic analysis of myocardial apoptosis was determined by TUNEL staining and caspase-3 activity., Results: HGHF treatment reduced mitochondrial biogenesis, altered mitochondrial structure, and induced mitochondrial dysfunction in NRVMs. Administration of APN partially rescued these effects. However, siRNA-mediated knockdown of peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1α) significantly blocked the beneficial effects of APN in mitochondria and cardiomyocytes subjected to hypoxia/reoxygenation injury., Conclusions: In the current study, we have provided the direct in vitro evidence that APN partially rescues HGHF-induced impairment of mitochondrial biogenesis and function via PGC-1α-mediated signaling.

Endometriosis is a common, complicated, and highly heterogeneous endocrine disease. Many genetic factors could affect the development of endometriosis. We performed a case-control study to evaluate the association between polymorphisms in CYP19A1 rs2899470, GSTM1, GSTT1, and GSTP1 rs1695 and the development of endometriosis in a Chinese population. Between March 2014 and October 2015, 262 endometriosis patients and 275 control subjects were recruited from the Inner Mongolia Medical University. Genotyping was conducted using polymerase chain reaction-coupled with restriction fragment length polymorphism. Individuals carrying the TT genotype of CYP19A1 rs2899470 expressed a higher risk of endometriosis than those carrying the GG genotype, and the adjusted ORs (95%CI) was 2.33 (1.27-4.33). Moreover, those with the TG + TT genotype were correlated with an elevated risk of endometriosis, compared to those with the GG genotype (OR = 1.48, 95%CI = 1.03-2.13). However, GSTM1, GSTT1, and GSTP1 rs1695 polymorphisms did not affect the pathogenesis of endometriosis. In conclusion, our results suggested that CYP19A1 rs2899470 polymorphism is associated with risk for endometriosis in the Chinese population.

Aims/introduction: Type 2 diabetes is a worldwide disease that is associated with increased rates of obesity and reduced physical activity. Obesity-associated insulin resistance in type 2 diabetes is a disorder in the balance between pro-inflammatory and anti-inflammatory signals. T cell immunoglobulin and mucin domain-containing molecule 3 (Tim-3) has been reported as an important regulatory inflammation molecule, and plays a pivotal role in several inflammation-related diseases., Materials and Methods: Peripheral blood mononuclear cells were obtained from type 2 diabetes patients (n = 31) and healthy donors (n = 18), and Tim-3 expression on peripheral blood mononuclear cells was evaluated by flow cytometry., Results: We showed the downregulated expression of Tim-3 on CD14 + monocytes from type 2 diabetes patients. In addition, the upregulated expression of Tim-3 on peripheral CD4 + T cells and CD8 + T cells was observed in the present study. The correlation analysis between Tim-3 expression on CD14 + monocytes and diabetes duration showed the longer diabetes duration time, the lower Tim-3 expression on CD14 monocytes., Conclusions: The present results suggest that Tim-3 might participate in the progression of type 2 diabetes by its negative regulation on these immune cells, and Tim-3 on CD14 + monocytes serves as a novel biological marker for diabetes duration in type 2 diabetes patients., (© 2016 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Curcumin, a type of natural active ingredient, is derived from rhizoma of Curcuma, which possesses antioxidant, antitumorigenic and anti‑inflammatory activities. The present study aimed to investigate whether treatment with curcumin reduced high‑fat diet (HFD)‑induced spermatogenesis dysfunction. Sprague‑Dawley rats fed a HFD were treated with or without curcumin for 8 weeks. The testis/body weight, histological analysis and serum hormone levels were used to evaluate the effects of curcumin treatment on spermatogenesis dysfunction induced by the HFD. In addition, the expression levels of apoptosis associated proteins, Fas, B‑cell lymphoma (Bcl)‑xl, Bcl‑associated X protein (Bax) and cleaved‑caspase 3, were determined in the testis. The results of the present study suggested that curcumin treatment attenuated decreased testis/body weight and abnormal hormone levels. Morphological changes induced by a HFD were characterized as atrophied seminiferous tubules, decreased spermatogenetic cells and interstitial cells were improved by curcumin treatment. In addition, curcumin treatment reduced apoptosis in the testis, and decreased expression of Fas, Bax and cleaved‑caspase 3, as well as increased expression of Bcl‑xl. In conclusion, the present study revealed that curcumin treatment reduced HFD‑induced spermatogenesis dysfunction in male rats.

Sirtuin 1 (Sirt1) is a class III histone deacetylase involved in neuroprotection induced by hyperbaric oxygen preconditioning (HBO-PC) in animal models of ischemia. However, the underlying mechanisms remain to be illustrated. In the present study, rats exposed to middle cerebral artery occlusion (MCAO) were used to establish an ischemic stroke model. The infarct volume ratio, neurobehavioral score, and expressions of Sirt1, nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), and superoxide dismutase 1 (SOD1) were evaluated at 7 days after reperfusion, and the level of malondialdehyde (MDA) was used to assess oxidative stress. HBO-PC increased the expression of Sirt1 and reduced infarct volume ratio and neurobehavioral deficit in MCAO rats. Meanwhile, HBO-PC also increased expression of Nrf2, HO-1, and SOD1 and decreased MDA content. Furthermore, either Sirt1 or Nrf2 knockdown by short interfering RNA (siRNA) inhibited the expression of Nrf2, HO-1, and SOD1 and eliminated the neuroprotective effects of HBO-PC. Taken together, the results suggest that the Nrf2/antioxidant defense pathway is involved in the long lasting neuroprotective effects of Sirt1 induced by HBO-PC against transient focal cerebral ischemia., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Piperlongumine (PL), a natural electrophilic alkaloid bearing two α, β-unsaturated imides, is a promising anticancer molecule by targeting the stress response to reactive oxygen species (ROS). Considering that ROS generation depends on electrophilicity of PL, PL-CL was designed as its analog by introducing the α-substituent chlorine on the lactam ring to increase moderately its electrophilicity. In comparison with the parent molecule, this molecule was identified as a stronger ROS (O2(∙-) and H2O2) inducer and cytotoxic agent, and manifested more than 15-fold selectivity toward A549 cells over normal WI-38 cells. Mechanistic study uncovers for the first time that the selenoprotein thioredoxin reductase (TrxR) is one of the targets by which PL-CL promotes the ROS generation. Stronger intracellular TrxR inhibition and higher accumulation of ROS (O2(∙-) and H2O2) are responsible for more effective S-phase arrest and mitochondria-mediated apoptotic induction of A549 cells by PL-CL than PLvia p53-p21-cyclinA/CDK2 and ASK1-JNK/p38 signaling cascade pathways, respectively. This work provides an example of successfully designing PL-directed anticancer agent by an electrophilicity-based prooxidant (ROS-generating agent) strategy and gives added confidence for extending this strategy to other natural products., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: To investigate the feasibility and safety of en bloc resection of cervical primary malignant bone tumors by a combined anterior and posterior approach based on a three-dimensional (3-D) printing model., Methods: Five patients with primary malignant bone tumors of the cervical spine underwent en bloc resection via a one-stage combined anteroposterior approach in our hospital from March 2013 to June 2014. They comprised three men and two women of mean age 47.2 years (range, 26-67 years). Three of the tumors were chondrosarcomas and two chordomas. Preoperative 3-D printing models were created by 3-D printing technology. Sagittal en bloc resections were planned based on these models and successfully performed. A 360° reconstruction was performed by spinal instrumentation in all cases. Surgical margins, perioperative complications, local control rate and survival rate were assessed., Results: All patients underwent en bloc excision via a combined posterior and anterior approach in one stage. Mean operative time and estimated blood loss were 465 minutes and 1290 mL, respectively. Mean follow-up was 21 months. Wide surgical margins were achieved in two patients and marginal resection in three; these three patients underwent postoperative adjuvant radiation therapy. One vertebral artery was ligated and sacrificed in each of three patients. Nerve root involved by tumor was sacrificed in three patients with preoperative upper extremity weakness. One patient (Case 3) had significant transient radiculopathy with paresis postoperatively. Another (Case 4) with C 4 and C 5 chordoma had respiratory difficulties and pneumonia after surgery postoperatively. He recovered completely after 2 weeks' management with a tracheotomy tube and antibiotics in the intensive care unit. No cerebrovascular complications and wound infection were observed. No local recurrence or instrumentation failure were detected during follow-up., Conclusion: Though technically challenging, it is feasible and safe to perform en bloc resection of cervical primary bone tumors. This is the most effective means of managing cervical spine tumors. Preoperative 3-D printing modelling enables better anatomical understanding of the relationship between the tumor and cervical spine and can assist in planning the surgical procedure., (© 2016 Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.)

Cleidocranial dysplasia (CCD), a skeletal disorder characterized by delayed permanent tooth eruption and other dental abnormalities, is caused by heterozygous RUNX2 mutations. As an osteoblast-specific transcription factor, RUNX2 plays a role in bone remodeling, tooth formation and tooth eruption. To investigate the crosstalk between RUNX2 and 1α,25-dihydroxyvitamin D3 (1α,25-(OH)2D3) in human dental follicle cells (hDFCs) during osteoclast formation, we established a co-culture system of hDFCs from CCD patient and healthy donors with peripheral blood mononuclear cells (PBMCs). Expression of the osteoclast-associated genes and the number of TRAP(+) cells were reduced in CCD hDFCs, indicating its suppressed osteoclast-inductive ability, which was reflected by the downregulated RANKL/OPG ratio. In addition, 1α,25-(OH)2D3-stimulation elevated the expression of osteoclast-related genes, as well as RANKL mRNA levels and RANKL/OPG ratios in control hDFCs. Conversely, RUNX2 mutation abolished this 1α,25-(OH)2D3-induced RANKL gene activation and osteoclast formation in CCD hDFCs. Therefore, RUNX2 haploinsufficiency impairs dental follicle-induced osteoclast formation capacity through RANKL/OPG signaling, which may be partially responsible for delayed permanent tooth eruption in CCD patients. Furthermore, this abnormality was not rescued by 1α,25-(OH)2D3 application because 1α,25-(OH)2D3-induced RANKL activation in hDFCs is mediated principally via the RUNX2-dependent pathway.

Breast cancer is one of the most commonly occurring female malignant tumors. According to the 2012 GLOBOCAN statistics, produced by the International Agency for Research On Cancer ('IARC'), nearly 1.7 million women were diagnosed with breast cancer, with 522,000 related deaths: An increase in the incidence of breast cancer and associated mortality by nearly 18% from 2008. Metastasis is the final step in breast cancer progression, and represents the most common cause of mortality in patients with breast cancer. Therefore, a search for low-toxicity, safe and effective anti-breast cancer drugs in the form of natural compounds has become an intense focus of research. Baicalein, a widely used Chinese herbal medicine, has extensive antitumor activity. The present review briefly describes the research that has been performed on the association between baicalein and breast cancer metastasis, and further illustrates the influence of baicalein on the underlying mechanisms of breast cancer metastasis, adding a novel theory basis for baicalein antitumor research. In conclusion, baicalein may represent a promising target for the prevention and therapy of breast cancer.

Selection of independent variable is a hotspot in the field of quantitative spectral analysis. Efficient and easy-to-use method for wavelength selection can not only reduce the computation and improve the accuracy of analysis, but also can reduce dependency on the spectral resolution of instruments and cut cost. Wavelength selection is also an important part of the research about noninvasive measurement of blood components by spectrum technology. Dynamic Spectrum theory provides excellent ideas for researchers, but only broadband light source and high-resolution spectrograph were used in correlational studies for a long time. The large number of wavelengths needed for analysis limits the further development of Dynamic Spectrum method. In order to remove redundancy information and make the devices low-cost and integrated, the method of Wavelength selection on the basis of Variable Importance in Projection (VIP) analysis was proposed. Variables with less importance were removed and wavelengths with great explanation power were retained after VIP analysis the number of wavelengths was reduced from 586 to 64. PLS model with 64 wavelengths get a satisfactory predict result that the MREP is 1.82%. The significance test through Bootstrap method validate the selected wavelengths’ explanation power. Moreover, the study pointed out the sensitive wavelengths in Dynamic Spectrum method for the first time. Study also took the first step toward the practical application of Dynamic Spectrum and laid the foundation of low-cost on-line analysis, and it also provided valuable references and new ideas for spectral analysis in other areas.

Bletilla striata has been used as traditional Chinese medicine for several centuries. In recent years, the quality and quantity of wild B. striata plants have declined sharply due to habitat deterioration and human over-exploitation. Therefore, it is of great urgency to evaluate and protect B. striata wild plant resource. In this study, sequence-related amplified polymorphism (SRAP) markers were applied to assess the level and pattern of genetic diversity in twelve populations of B. striata. The results showed a high level of genetic diversity (PPB = 90.48%, H = 0.349 4, I = 0.509 6) and moderate genetic differentiation among populations (G(st) = 0.260 9). Based on the unweighted pair-group method with arithmetic average (UPGMA), twelve populations gathered in three clusters. The cluster 1 included four populations. There are Nanjing, Zhenjiang, Xuancheng and Hangzhou. The seven populations which come from Hubei Province, Hunan Province, Jiangxi Province and Guizhou Province belonged to the cluster 2. The cluster 3 only contained Wenshan population. Moreover, Mantel test revealed significant positive correlation between genetic distances and geographic distances (r = 0.632 9; P < 0.000 1). According to the results, we proposed a series of conservation consideration for B. striata.

Micro-expressions are brief involuntary facial expressions that reveal genuine emotions and, thus, help detect lies. Because of their many promising applications, they have attracted the attention of researchers from various fields. Recent research reveals that two perceptual color spaces (CIELab and CIELuv) provide useful information for expression recognition. This paper is an extended version of our International Conference on Pattern Recognition paper, in which we propose a novel color space model, tensor independent color space (TICS), to help recognize micro-expressions. In this paper, we further show that CIELab and CIELuv are also helpful in recognizing micro-expressions, and we indicate why these three color spaces achieve better performance. A micro-expression color video clip is treated as a fourth-order tensor, i.e., a four-dimension array. The first two dimensions are the spatial information, the third is the temporal information, and the fourth is the color information. We transform the fourth dimension from RGB into TICS, in which the color components are as independent as possible. The combination of dynamic texture and independent color components achieves a higher accuracy than does that of RGB. In addition, we define a set of regions of interests (ROIs) based on the facial action coding system and calculated the dynamic texture histograms for each ROI. Experiments are conducted on two micro-expression databases, CASME and CASME 2, and the results show that the performances for TICS, CIELab, and CIELuv are better than those for RGB or gray.

Rheumatoid arthritis is an autoimmune disease characterized as joint synovial inflammation. MicroRNA is a group of small noncoding RNA molecules discovered in recent years that can posttranscriptional regulate mRNA expression and involved in a variety processes of immune cell activation and differentiation. There is still lack of study about the role of miR-451 in rheumatoid arthritis. Synovial fibroblasts isolated from rheumatoid arthritis patients were cultured in vitro. Chemical synthesized miR-451 was lipo-transfected, real-time RT-PCR was applied to detect miR-451 expression level, and MTT method was used to detect the effect of miR-451 on synovial fibroblasts proliferation. Enzyme-linked immunosorbent assay was used to detect tumor necrosis factor TNF-α, IL-1β, and IL-6 level in the supernatant. Western blot was applied to test target protein p38 MAPK expression level. Our study found that synovial fibroblasts expressed higher miR-451 mRNA level in miR-451 treatment group. MiR-451 treatment significantly decreased cell proliferation ability (P < 0.05). Compared with the control, p38 MAPK protein expression reduced obviously in the miR-451 treatment group (P < 0.05). MiR-451 transfected synovial fibroblasts secreted lower levels of TNF-α (198 ± 12 pg/ml vs 124 ± 13 pg/ml, P < 0.01), IL-1β (352 ± 43 pg/ml vs 165 ± 87 pg/ml, P < 0.01), and IL-6 (487 ± 84 pg/ml vs 257 ± 92 pg/ml, P < 0.01). The results proved that miR-451 can down-regulate p38 MAPK protein expression, and reduce synovial fibroblasts proliferation and cytokine expression level.

The interferon-inducible transmembrane protein 3 (IFITM3), as one of the key genes involved in the interferon pathway, is critical for defending the host against influenza virus, and the rs12252 T>C variant in IFITM3 might be associated with susceptibility to severe influenza. Owing to contradictory and inconclusive results, we performed a meta-analysis to assess the association between rs12252 T>C polymorphism and severe influenza risk. A comprehensive literature search up to 1 August 2014 was conducted in EMBASE, Pubmed, Web of Science, VIP, Wanfang and CNKI databases. Four eligible studies with a total of 445 influenza patients and 3396 controls were included in this meta-analysis. Overall, our results demonstrated a significant association between the IFITM3 rs12252 T>C polymorphism and influenza risk [C vs. T: odds ratio (OR) 1·68, 95% confidence interval (CI) 1·32-2·13; CC vs. CT+TT: OR 2·38, 95% CI 1·52-3·73; CC+CT vs. TT: OR 1·62, 95% CI 1·18-2·22]. Stratification by ethnicity indicated that the variant C allele was associated with an 88% increased risk of influenza in Asians (C vs. T: OR 1·88, 95% CI 1·34-2·62). Moreover, subjects carrying the variant C allele had an increased risk of developing severe illness upon influenza infection (C vs. T: OR 2·70, 95% CI 1·86-3·94). However, no significant association was observed in patients with mild infection (C vs. T: OR 1·26, 95% CI 0·93-1·71). Our meta-analysis suggests that IFITM3 rs12252 T>C polymorphism is significantly associated with increased risk of severe influenza but not with the chance of initial virus infection.

Background: Ovarian stimulation in IVF cycle results in luteal supraphysiological steroid concentrations especially for high response patients. The aim of this study was to evaluate the efficacy of ovarian steroid hormone suppression in luteal phase after oocyte retrieval for preventing severe ovarian hyperstimulation syndrome (OHSS) in high-risk patients with embryo cryopreservation., Methods: 281 patients with high risk of OHSS were enrolled in this study among 4735 infertile women undergoing their first IVF treatment. The subjects were allocated into treatment and control group. The treatment group (n = 161) received letrozole (n = 43), mifepristone (n = 51), cetrotide (n = 39) and three-drug combinations (n = 28) during the luteal phase after oocyte retrieval, respectively. The control group (n = 120) received no medicine. Fertilization rate, good embryo rate, serum steroid concentration, clinical outcome, and incidence of severe OHSS were compared between the two groups., Results: On days 2, 5 and 8 after oocyte retrieval, serum estradiol levels in the letrozole and three-drug combination therapy group were significantly lower than in the other three groups at the same time (P < 0.001, respectively). There were no significantly difference of serum luteinizing hormone concentration on days 2, 5 and 8 and progesterone concentration on day 8 after oocyte retrieval among the five groups (P > 0.05, respectively). Compared with the control group, the incidence of severe OHSS, the paracentesis rate, the duration of hospitalization and the days of luteal phase in each subgroup of treatment groups was not significantly decreased (P > 0.05, respectively)., Conclusions: Our findings indicate that steroidal ovarian suppression in luteal phase after oocyte retrieval seems to be unable to prevent severe OHSS in high-risk patients with embryo cryopreservation.

Curcumin, derived from the dietary spice turmeric, holds promise for cancer prevention. This prompts much interest in investigating the action mechanisms of curcumin and its analogues. Two symmetrical hexamethoxy-diarylpentadienones (1 and 2) as cucumin analogues were reported to possess significantly enhanced cytotoxicity compared with the parent molecule. However, the detailed mechanisms remain unclear. In this study, compounds 1 and 2 were identified as the G2/M cell cycle arrest agents to mediate the cytotoxicity toward NCI-H460 cells via Michael acceptor-dependent redox intervention. Compared with curcumin, they could more easily induce a burst of reactive oxygen species (ROS) and collapse of the redox buffering system. One possible reason is that they could more effectively target intracellular TrxR to convert this antioxidant enzyme into a ROS promoter. Additionally, they caused up-regulation of p53 and p21 and down-regulation of redox-sensitive Cdc25C along with cyclin B1/Cdk1 in a Michael acceptor- and ROS-dependent fashion. Interestingly, in comparison with compound 2, compound 1 displayed a relatively weak ability to generate ROS but increased cell cycle arrest activity and cytotoxicity probably due to its Michael acceptor-dependent microtubule-destabilizing effect and greater GST-inhibitory activity, as well as its enhanced cellular uptake. This work provides useful information for understanding Michael acceptor-dependent and redox-mediated cytotoxic mechanisms of curcumin and its active analogues.

Objective: Studies in animal models have indicated that Pellino 1 is involved in inflammatory and autoimmune diseases, such as systemic lupus erythematosus (SLE). The current study was designed to determine whether PELI1 confers genetic susceptibility to SLE in humans, as assessed in a Chinese Han population., Methods: Blood samples were drawn from patients diagnosed with SLE and healthy volunteers. Three single nucleotide polymorphism (SNP) loci with a minor allele frequency of at least 0.05 were chosen to evaluate the correlation between PELI1 genotype and the incidence of SLE., Results: There was a significant difference in the frequency distribution of the rs329497 allele between the SLE patients and the healthy controls (A vs. G; Bonferroni corrected p = 0.036, odds ratio = 0.75, 95% confidence interval = 0.60-0.94). No differences in the genotype and allele frequencies of other SNP loci were observed between the two groups. Furthermore, the alleles and genotypes of the three SNPs were not associated with lupus nephritis., Conclusion: In the Chinese Han population, PELI1 SNPs may be associated with SLE susceptibility., (© The Author(s) 2015.)

Developing anticancer agents by a prooxidant strategy has attracted increasing attention in recent years, although it is not conventional in medicinal chemistry and is completely opposite to antioxidant therapy. In this work, a panel of diarylpentanoids as the curcumin mono-carbonyl analogs were designed and synthesized, and their cytotoxic and proapoptotic mechanisms against human lung cancer A549 cells were investigated at the frontiers of chemistry and biology. It was found that compared with curcumin, the compounds (A1, B1, and C1) bearing two ortho substituents on the aromatic rings, especially A1, exhibit significantly increased cytotoxic and proapoptotic activities through a Michael acceptor unit-dependent prooxidant-mediated mechanism. The prooxidative ability is governed not only by their electrophilicity but also by their geometry, cellular uptake and metabolic stability, and TrxR-inhibitory activity. Mechanistic investigation reveals that the compound A1 could effectively and irreversibly modify the TrxR by virtue of the above optimal biochemical parameters, and convert this antioxidant enzyme into a reactive oxygen species (ROS) promoter, resulting in a burst of the intracellular ROS including H2O2 and O2(-)•. The ROS generation is associated with falling apart in the redox buffering system, and subsequently induces increases in Ca(2+) influx and oxidative stress, collapse of mitochondrial membrane potential, and activation of caspase-9 and caspase-3, ultimately leading to cell apoptosis. This work highlights the feasibility in designing curcumin-inspired anticancer agents by a prooxidant strategy, and gives us useful information on how to design them., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: To discuss early efficacy of the cardiac patient with giant left ventricle underwent valve replacement., Patients and Methods: Fifty-five patients, who are suffering cardiac valve disease with giant left ventricle, underwent valve replacement. Among them, sixteen patients underwent aortic valve replacement; thirty patients underwent mitral valve replacement; nine patients underwent double valve replacement. All of them use mechanical heart valve., Results: The number of early death after operation was five. Two patients died of malignant arrhythmia; two died of intractable low cardiac output syndrome; the last one's mechanical valve lost its ability to function after operation and died of respiration-circulation failure after an emergency operation. The death rate was 9%. The remaining 55 patients were cured and their cardiac function was significantly improved., Conclusions: The definite effective myocardial protection and perfect and detailed preoperative treatment can reduce the possibility of operative complications and death rate of this kind of patients.

Purpose: The goal of this study was to quantitatively identify the differentially expressed proteins in nuclear cataracts of different ages and normal lens nuclei in humans., Experimental Design: Forty-eight human lens nucleus samples with hardness grades III, IV were obtained during cataract surgery by extracapsular cataract extraction. Seven normal transparent human lens nuclei were obtained from fresh normal cadaver eyes during corneal transplantation surgery. Lens nuclei were divided into seven groups according to age and optic axis: Group A (average age 80.8 ± 1.2 years), Group B (average age 57.0 ± 4.0 years), Group C average age 80.3 ± 4.5 years), Group D (average age 56.9 ± 4.2 years), Group E (average age 78.1 ± 2.5 years), Group F (average age 57.6 ± 3.3 years) and Group G (seven normal transparent human lenses from normal cadaver eyes, average age 34.7 ± 4.2 years). Water-soluble, water-insoluble, and water-insoluble-urea-soluble protein fractions were extracted from samples. The three-part protein fractions from the individual lenses were combined to form the total proteins of each sample. The proteomic profiles of each group were further analyzed using 8-plex iTRAQ labeling combined with 2D-LC-MS/MS. The data were analyzed with the ProteinPilot software for peptide matching, protein identification, and quantification. Differentially expressed proteins were validated by Western blotting., Results: We employed biological and technical replicates and selected the intersection of the two results, which included 80 proteins. Nine proteins were differentially expressed among the 80 proteins identified using proteomic techniques. In age-related nuclear cataracts (ARNC), the expression levels of fatty acid-binding protein and pterin-4-alpha-carbinolamine dehydratase were upregulated, whereas the levels of alpha-crystallin B chain (CRYAB), GSH synthetase, phakinin, gamma-crystallin C, phosphoglycerate kinase 1, betaine-homocysteine S-methyltransferase 1 (BHMT1), and spectrin beta chain were downregulated. These proteins may be associated with abnormal protein aggregation and oxidative stress. GSH synthetase and CRYAB expression levels in the nuclear cataract decreased with age. The mass spectrometric analysis results were consistent with the Western blot validation., Conclusion and Clinical Relevance: The results indicate that CRYAB and GSH synthetase may be involved in ARNC pathogenesis. iTRAQ combined with 2D-LC-MS/MS provides new methods for future studies of pathological mechanisms and protective drug development for ARNC., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Purpose: The study aims to elucidate the changes in testicular spermatogenic function in high-fat diet (HFD)-induced obese rats and to evaluate the protective effects of metformin intervention., Methods: Male Sprague-Dawley rats (n = 18) were randomly divided into a control group (standard diet), an HFD group, and a metformin group (HFD + metformin at 100 mg/kg, once daily by oral gavage). After 8 weeks, rats were euthanized, and the weights of body and testes were measured. Testis and epididymis were dissected and hematoxylin-eosin-stained for histopathological examination and semen parameter analysis. Blood samples were collected for assessment of sex hormones and metabolic parameters (serum glucose, insulin, and leptin). Spermatogenic cell apoptosis was accessed by TUNEL., Results: Compared with the control group, the final body weight and weight gain were significantly higher in HFD rats, while the testicle weight and coefficients were lower. In HFD rats, metformin treatment induced weight loss and increased testicle weight (P < 0.05). In HFD rats, obvious pathological changes in the testicular tissue were characterized by small, atrophic, and distorted seminiferous tubules and destroyed basement membrane. Metformin treatment protected against the HFD-induced decrease in the number of spermatogonia, Sertoli cells, and Leydig cells (P < 0.05); ameliorated the HFD-induced increases in serum glucose, insulin, leptin, and estrogen; and decreased serum testosterone (P < 0.05) and reduced the rate of testicular cell apoptosis in obese male rats. Finally, metformin significantly improved semen parameters (including concentration, viability, motility, and normal morphology) in HFD rats (P < 0.05)., Conclusions: HFD-induced obesity in rats results in detrimental effects on spermatogenesis, semen quality, endogenous hormones, and testicular cell apoptosis. Metformin intervention improved the semen parameters, possibly due to its effects on weight loss, increased testicular weight, reduced testicular cell apoptosis, and resulted in restoration of hormonal homeostasis and correction of metabolic disorder.

The present study used a single-task paradigm in which participants received guidance to focus more attention (waiting for someone) on the temporal intervals in the "waiting" condition and to stay relaxed in the control condition. The reported time was longer in the waiting condition than in the control condition. Functional near-infrared spectroscopy was used to measure simultaneously the activation levels of the dorsolateral prefrontal cortex (DLPFC) for each condition. Greater oxyhemoglobin (oxy-Hb) activation in the waiting condition was observed compared with the control condition, whilst deoxyhemoglobin data showed no difference between the two conditions. The gradual changes in oxy-Hb in the DLPFC in increments of 100 ms yielded further insights into the role of this region in the "watched pot never boils" phenomenon., (© 2014 The Institute of Psychology, Chinese Academy of Sciences and Wiley Publishing Asia Pty Ltd.)

Silibinin, a natural flavonoid antioxidant isolated from extracts of the milk thistle herb, has recently been identified as having anti-hepatotoxic and anticancer properties. In this paper, we investigated the effects of silibinin on behavior and neuroplasticity in mice subjected to chronic unpredictable mild stress (CUMS). After 5 consecutive weeks of CUMS, the mice were treated with silibinin (100 mg/kg, 200 mg/kg and 400 mg/kg by oral gavage) for 3 consecutive weeks. The results showed that silibinin administration significantly alleviated the CUMS-induced depressive-like behavior, including the total number of squares crossed and the frequency of rearing in the open field test, the immobility time in the tail suspension test and the forced swimming test. Furthermore, silibinin treatment increased the levels of brain-derived neurotrophic factor (BDNF), serotonin (5-HT) and norepinephrine (NE) in the prefrontal cortex and hippocampus. Our study provides new insight into the protective effects of silibinin on the depressive status of CUMS mice, specifically by improving neuroplasticity and neurotransmission.

Cleidocranial dysplasia (CCD) is a skeletal dysplasia caused by heterozygous mutations of RUNX2, a gene that is essential for the mineralization of bone and tooth. We isolated primary dental pulp cells from a 10-y-old patient and tested their proliferative capacity, alkaline phosphatase activity, and ability to form mineralized nodules, in comparison with those from 7 healthy children. All these measures were reduced in primary dental pulp cells from the CCD patient. The expression of the osteoblast/odontoblast-associated genes RUNX2, ALP, OCN, and DSPP was also found to be significantly decreased in the primary dental pulp cells of the CCD patient. The osteoclast-related markers TRAP, CTSK, CTR, and MMP9 were decreased in primary dental pulp cells cocultured with human peripheral blood mononuclear cells. Moreover, the expression of RANKL and the ratio of RANKL/OPG were both reduced in the cells from the CCD patient, indicating that the RUNX2 mutation interfered with the bone-remodeling pathway and decreased the capacity of primary dental pulp cells to support osteoclast differentiation. These effects may be partly responsible for the defects in tooth development and the retention of primary teeth that is typical of CCD., (© International & American Associations for Dental Research 2015.)

Objective: To explore the early dental interventional strategies for adolescent patients and a child patient with cleidocranial dysplasia (CCD)., Methods: Surgical exposure using the apically repositioned flap technique combined with orthodontic traction was used in the adolescent patients whose ideal treatment time for initiating treatment was missed. For the child patient whose ideal treatment time for initiating treatment was not missed, the simple surgical exposure method was carried out in order to promote the eruption of the impacted incisors., Results: All the impacted maxillary incisors of the three CCD patients were successfully positioned into a proper alignment either through the two stages of crown exposure and the elastic traction or simple surgical exposure., Conclusion: Crown exposure surgery combined with light force orthodontic traction provides an effective approach to treat the typical dental abnormalities of adolescent CCD patients. Simple surgical exposure was also an effective way for a child CCD patient for whom the most ideal time for initiation of treatment was not missed.

Our goal was to analyze the anatomical parameters of the lumbar spine spinous process for an interspinous stabilization device designed for the Chinese population and to offer an anatomical basis for its clinical application. The posterior lumbar spines (T12-S1) of 52 adult cadavers were used for measuring the following: distance between two adjacent spinous processes (DB), distance across two adjacent spinous processes (DA), thickness of the central spinous processes (TC), thickness of the superior margin of the spinous processes (TS), thickness of the inferior margin of the spinous processes (TI), and height of the spinous processes (H). Variance and correlation analyses were conducted for these data, and the data met the normal distribution and homogeneity of variance. DB decreased gradually from L1-2 to L5-S1. DA increased from T12-L1 to L2-3 and then decreased from L2-3 to L4-5. The largest H in males was noted at L3 (25.45±5.96 mm), whereas for females the largest H was noted at L4 (18.71±4.50 mm). Usually, TS of the adjacent spinous process was lower than TI. Based on the anatomical parameters of the lumbar spinous processes obtained in this study, an "H"-shaped coronal plane (posterior view) was proposed as an interspinous stabilization device for the Chinese population. This study reports morphometric data of the lumbar spinous processes in the Chinese population, which provides an anatomical basis for future clinical applications.

The aim of the present pilot study was to assess the feasibility and efficacy of Cetrotide administration in the early luteal phase in patients at high risk of ovarian hyperstimulation syndrome (OHSS), undergoing embryo cryopreservation following superovulation. A total of 135 patients at high risk of OHSS and undergoing embryo cryopreservation were divided into two groups. In the treatment group (n=39), the patients received daily subcutaneous injections of 0.25 mg Cetrotide between days 1 and 5 following ooctye retrieval, and volume expansion and symptomatic treatment were also provided. In the control group (n=96), the patients received routine treatments, including volume expansion therapy. The serum steroid hormone concentrations of the patients were measured on days 2, 5 and 8 following ooctye retrieval, while the incidence of moderate or severe OHSS, self-evaluated clinical symptoms and various clinical indicators were recorded. The serum estradiol (E 2 ), luteinizing hormone and progesterone levels in the treatment group on days 2, 5 and 8 following oocyte retrieval were not found to differ significantly when compared with the patients in the control group (P>0.05). The incidence of severe OHSS did not differ significantly between the two groups (P>0.05). The average length of hospital stay and length of luteal phase were not found to be significantly different between the treatment and control groups (P>0.05). In conclusion, Cetrotide injections in the early luteal phase did not alter the serum steroid levels of patients at high risk of OHSS undergoing embryo cryopreservation, and were unable to reduce the incidence of severe early OHSS. However, further randomized studies are required to evaluate the effectiveness of Cetrotide in the prevention of OHSS.

We investigated serum folic acid (FA) levels in patients with erectile dysfunction (ED) and/or premature ejaculation (PE). Fasting serum samples were obtained from 42 patients with ED, 36 with PE, 25 ED patients with PE, and 30 healthy men; the mean intravaginal ejaculation latency time (IELT) was measured during a 4 weeks baseline period. Levels of sex hormones (follicle-stimulating hormone, luteinizing hormone, total testosterone), homocysteine (Hcys), and FA were measured using chemiluminescent immunoassays. The sexual functions of PE patients and normal control men were evaluated using the Chinese Index of Premature Ejaculation (CIPE). The abridged International Index of Erectile Function-5 (IIEF-5) questionnaire was used to gauge erectile quality for ED patients and for normal controls. Serum FA concentrations were lower in ED (7.61 ± 3.97 ng ml⁻¹), PE (9.37 ± 3.40 ng ml⁻¹), and ED/PE (8.84 ± 4.28 ng ml⁻¹) patients than in healthy men (12.23 ± 5.76 ng ml -1 , P < 0.05). No significant differences in sex hormone levels were found between patients with sexual dysfunction and healthy controls (P > 0.05). There were positive correlations between serum FA concentrations and CIPE scores (r = 0.530, P < 0.01), IIEF-5 scores (r = 0.589, P < 0.01), and IELT (r = 0.445, P < 0.01); negative correlations with Hcys concentrations (r = -0.487, P < 0.01) were found in all participants. These findings showed a strong relationship between serum FA levels and sexual dysfunction, possibly due to an effect of FA on the metabolism of nitric oxide, Hcys, and 5-hydroxytryptamine.

Background: Endothelial dysfunction is implicated in the initiation and progression of atherosclerosis. Whether atorvastatin combined with rosiglitazone has synergistic effects on endothelial function improvement in the setting of dyslipidemia is unknown., Methods: Dyslipidemia rat model was produced with high-fat and high-cholesterol diet administration. Thereafter, atorvastatin, rosiglitazone or atorvastatin combined with rosiglitazone were prescribed for 2 weeks. At baseline, 6 weeks of dyslipidemia model production, and 2 weeks of medical intervention, fasting blood was drawn for parameters of interest evaluation. At the end, myocardium was used for 15-deoxy-delta-12,14-PGJ2 (15-d-PGJ2) assessment., Results: Initially, there was no significant difference of parameters between sham and dyslipidemia groups. With 6 weeks' high-fat and high-cholesterol diet administration, as compared to sham group, serum levels of triglyceride (TG), total cholesterol (TC) and low density lipoprotein-cholesterol (LDL-C) were significantly increased. Additionally, nitric oxide (NO) production was reduced and serum levels of malondialdehyde (MDA), C-reactive protein (CRP) and asymmetric dimethylarginine (ADMA) were profoundly elevated in dyslipidemia group. After 2 weeks' medical intervention, lipid profile was slightly improved in atorvastatin and combined groups as compared to control group. Nevertheless, in comparison to control group, NO production was profoundly increased and serum levels of MDA, CRP and ADMA were significantly decreased with atorvastatin or rosiglitazone therapy. 15-d-PGJ2 expression of myocardium was also significantly elevated with atorvastatin or rosiglitazone treatment. Notably, these effects were further enhanced with combined therapy, suggesting that atorvastatin and rosiglitazone had synergistic effects on endothelial protection, and inflammation and oxidation amelioration., Conclusion: Atorvastatin and rosiglitazone therapy had synergistic effects on endothelium protection as well as amelioration of oxidative stress and inflammatory reaction in rats with dyslipidemia.

Tumor necrosis factor-α-inducible protein-1 (TNFAIP1) plays a role in DNA synthesis, DNA repair, cell apoptosis and human diseases including cancer, and may be involved in tumor progression and metastases. However, little is known concerning the function of TNFAIP1 in human osteosarcoma (OS). The aim of the present study was to investigate the function and underlying mechanisms of TNFAIP1 in human OS. The expression of TNFAIP1 was examined by immunohistochemical assay using a tissue microarray procedure. A loss-of-function experiment was performed to explore the effects of lentiviral-mediated TNFAIP1 siRNA (siTNFAIP1) on cell proliferation, invasive potential and apoptosis by MTT and Transwell assays and flow cytometric analysis in OS (MG-63 and U-2 OS) cells. The results showed that the expression of TNFAIP1 protein was significantly increased in OS tissues compared with that in adjacent non-cancerous tissues (ANCTs) (73.3 vs. 48.9%, P=0.018), and was correlated with the distant metastasis of the patients with OS (P=0.029). Knockdown of TNFAIP1 suppressed cell proliferation and invasion, and induced cell apoptosis in the OS cells together with the downregulation of p65 nuclear factor-κB (NF-κB), proliferating cell nuclear antigen (PCNA) and matrix metalloproteinase-2 (MMP-2) and upregulation of caspase-3. Collectively, our findings indicate that high expression of TNFAIP1 is associated with distant metastasis of OS, and knockdown of TNFAIP1 inhibits the growth and invasion, and induces apoptosis in OS cells through inhibition of the NF-κB pathway, suggesting that TNFAIP1 may act as a potential therapeutic target for the treatment of cancer.

Four novel compounds were designed by "tailoring" 3,3'-dihydroxyisorenieratene (a natural carotenoid) based on an isoprene unit retention truncation strategy. Among them, the smallest molecule 1 (2,3,6,2',3',6'-hexamethyl-4,4'-dihydroxy-trans-stilbene) was concisely synthesized in a one-pot Stille-Heck tandem sequence, and surfaced as a promising lead molecule in terms of its selective antiproliferative activity mediated by blocking the NCI-H460 cell cycle in G1 phase. Additionally, theoretical calculations and cell uptake experiments indicate that the unique polymethylation pattern of compound 1 significantly induces a conformational change shift out of planarity and increases its cell uptake and metabolic stability. The observation should be helpful to rationally design resveratrol-inspired antiproliferative agents., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A robust automatic micro-expression recognition system would have broad applications in national safety, police interrogation, and clinical diagnosis. Developing such a system requires high quality databases with sufficient training samples which are currently not available. We reviewed the previously developed micro-expression databases and built an improved one (CASME II), with higher temporal resolution (200 fps) and spatial resolution (about 280×340 pixels on facial area). We elicited participants' facial expressions in a well-controlled laboratory environment and proper illumination (such as removing light flickering). Among nearly 3000 facial movements, 247 micro-expressions were selected for the database with action units (AUs) and emotions labeled. For baseline evaluation, LBP-TOP and SVM were employed respectively for feature extraction and classifier with the leave-one-subject-out cross-validation method. The best performance is 63.41% for 5-class classification.

Objective: To explore the efficiency of using aromatase inhibitors during luteal phase in in vitro fertilization IVF stimulated cycles for patients at high risk for ovarian hyperstimulation syndrome (OHSS)., Methods: A total of 139 infertile women undergoing assisted reproductive technique with high risk for OHSS were enrolled in this clinical trial. In the treatment group 43 patients received five consecutive doses of aromatase inhibitors (letrozole) and support therapy combined with embryo cryopreservation. In the control group 96 patients received support therapy alone. All the patients were evaluated clinically, echographically, hematologically and tested for their steroid hormone., Results: There was significantly lower estrogen level in the treatment group 2, 5 and 8 days after oocyte retrieval compared with the control group (P<0.001), There was no significant difference in luteinizing hormone and progesterone levels 2, 5 and 8 days after oocyte retrieval in the treatment group and control group (P>0.05). There were 7 cases of severe OHSS in the treatment group and 18 cases of severe OHSS in the control group. The rate of severe OHSS was not significantly different in the treatment group and control group (P=0.12). No side effect was reported in either group., Conclusion: Treatment with letrzolein luteal phase decreases serum estrogen levels of patients after oocyte retrieval,but it couldn't reduce the risk of severe OHSS.