Selective and controllable amination and defluoroamidation of α-trifluoromethylstyrene.

We present a blueprint for the amination and defluoroamidation of α-trifluoromethylstyrene. This practical protocol presents a general method for the diversity-oriented synthesis of vicinal trifluoromethyl amines and gem-difluoro alkenes from α-trifluoromethylstyrene maintaining excellent chemoselectivity. The synthetic strategy features outstanding atom economy and wide functional group tolerance under mild reaction conditions.

[Screening of Amendments for Simultaneous Cd and As Immobilization in Soil].

Simultaneously reducing the availability of Cd and As is difficult owing to converse chemical behaviors of Cd and As in soil. In this study, amendments that can simultaneously immobilize Cd and As in soil were determined by an pure soil culture experiment in which flooding and wetting were performed for 30 d each. The effects of sepiolite (Sep), modified sepiolite (IMS and Sep-FM), steel slag (SS), and iron modified biochar (Fe-Bio) on soil pH, Eh, Cd, and As concentrations in pore water, and Cd and As fractions in soil were investigated. It showed that Sep (1%, 2.5%), IMS (1%, 2.5%), Sep-FM (1%, 2.5%), and SS (1%, 5%) treatments increased soil pH value and decreased Eh value and Cd concentrations in soil solution. In addition, As concentrations in soil solution treated with high doses of IMS (2.5%) and SS (5%) were lower than that of CK treatment during the whole incubation period. However, Fe-bio treatment decreased soil pH and increased Eh value and only decreased Cd and As concentrations in soil solution under wet conditions. Compared with the control, the application of the above amendments promoted the transformation of Cd fraction from exchangeable to reducible, oxidizable, and residual. High application rates of IMS (2.5%), Sep-FM (2.5%), and SS (5%) also reduced available As fraction (non-specifically sorbed and specifically-sorbed As fraction), and increased amorphous and poorly-crystalline hydrated Fe and Al oxide-bound As. On the contrary, Fe-bio treatment increased the fractions of non-specifically sorbed, specifically sorbed and residual As in soil. In short, IMS, Sep-FM, and SS are potential materials for remediation of Cd and As contaminated soil. They can effectively immobilize soil Cd and As and promote their transformation to the fractions that plants are difficult to uptake.

The role of advanced glycation end products in human infertility.

Advanced glycation end products (AGEs) are heterogeneous products of the non-enzymatic interaction between proteins and reducing sugars. Numerous studies have shown that AGEs are associated with senescence, diabetes, vascular disease, aging and kidney disease. Infertility has been affected approximately 10 to15% of couples of reproductive ages. AGEs accumulation has been shown to play a crucial role in pathogenesis of infertility-related diseases. The present review provides the generation process, mechanism and pathological significance of AGEs and the novel treatment targeting AGEs for infertility.

Deep Learning-Based Recognizing COVID-19 and other Common Infectious Diseases of the Lung by Chest CT Scan Images

PurposeCOVID-19 has become global threaten. CT acts as an important method of diagnosis. However, human-based interpretation of CT imaging is time consuming. More than that, substantial inter-observer-variation cannot be ignored. We aim at developing a diagnostic tool for artificial intelligence (AI)-based classification of CT images for recognizing COVID-19 and other common infectious diseases of the lung. Experimental DesignIn this study, images were retrospectively collected and prospectively analyzed using machine learning. CT scan images of the lung that show or do not show COVID-19 were used to train and validate a classification framework based on convolutional neural network. Five conditions including COVID-19 pneumonia, non-COVID-19 viral pneumonia, bacterial pneumonia, pulmonary tuberculosis, and normal lung were evaluated. Training and validation set of images were collected from Wuhan Jin Yin-Tan Hospital whereas test set of images were collected from Zhongshan Hospital Xiamen University and the fifth Hospital of Wuhan. ResultsAccuracy, sensitivity, and specificity of the AI framework were reported. For test dataset, accuracies for recognizing normal lung, COVID-19 pneumonia, non-COVID-19 viral pneumonia, bacterial pneumonia, and pulmonary tuberculosis were 99.4%, 98.8%, 98.5%, 98.3%, and 98.6%, respectively. For the test dataset, accuracy, sensitivity, specificity, PPV, and NPV of recognizing COVID-19 were 98.8%, 98.2%, 98.9%, 94.5%, and 99.7%, respectively. ConclusionsThe performance of the proposed AI framework has excellent performance of recognizing COVID-19 and other common infectious diseases of the lung, which also has balanced sensitivity and specificity.

Mitochondrial Dysfunction in Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is one of the most common female reproductive metabolisms. It is an endocrine disease that affects reproductive women and often exhibits with hyperandrogenemia, insulin resistance (IR), low inflammation, and an increased risk of type 2 diabetes mellitus, metabolic syndrome, and cardiovascular events such as hypertension and dyslipidemia in patients. However, the molecular mechanism of PCOS is still unclear. Recently, an increasing number of studies have shown that the oxidative stress induced by mitochondrial dysfunction has negative effects on IR, lipid metabolism, and follicular development, suggesting that mitochondrial dysfunction plays an essential role in the development of PCOS. Abnormal mitochondrial DNA copy number in patients with PCOS, and mitochondrial gene mutations, has been the focus of research in recent years, and functional mitochondrial diseases have been gradually accepted as a related factor in PCOS. This review is intended to summarize and discuss previous and recent studies and findings on the connections between mitochondrial dysfunction and PCOS.

Polycystic ovarian syndrome: Correlation between hyperandrogenism, insulin resistance and obesity.

Polycystic ovary syndrome (PCOS) is a complex and heterogeneous endocrine disease characterized by clinical or laboratorial hyperandrogenism, oligo-anovulation and metabolic abnormalities, including insulin resistance, excessive weight or obesity, type II diabetes, dyslipidemia and an increased risk of cardiovascular disease. The most significant clinical manifestation of PCOS is hyperandrogenism. Excess androgen profoundly affects granulosa cell function and follicular development via complex mechanisms that lead to obesity and insulin resistance. Most PCOS patients with hyperandrogenism have steroid secretion defects that result in abnormal folliculogenesis and failed dominant follicle selection. Hyperandrogenism induces obesity, hairy, acne, and androgenetic alopecia. These symptoms can bring great psychological stress to women. Drugs such as combined oral contraceptive pills, metformin, pioglitazone and low-dose spironolactone help improve pregnancy rates by decreasing androgen levels in vivo. Notably, PCOS is heterogeneous, and hyperandrogenism is not the only pathogenic factor. Obesity and insulin resistance aggravate the symptoms of hyperandrogenism, forming a vicious cycle that promotes PCOS development. Although numerous studies have been conducted, the definitive pathogenic mechanisms of PCOS remain uncertain. This review summarizes and discusses previous and recent findings regarding the relationship between hyperandrogenism, insulin resistance, obesity and PCOS.

Sex hormone-binding globulin and polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS), one of the most common endocrine diseases that causes infertility in reproductive women, is characterized by hyperandrogenemia, chronic anovulation, and polycystic ovary morphology (PCOM), and most women with PCOS have metabolic abnormalities. A reduction in plasma sex hormone-binding globulin (SHBG), a transport carrier that binds estrogen and androgens and regulates their biological activities, is often used as an indicator of hyperandrogenism in women with PCOS. Low serum SHBG levels are considered a biomarker of abnormal metabolism and are related to insulin resistance (IR), compensatory hyperinsulinemia and abnormalities in glucose and lipid metabolism in PCOS patients. SHBG is also associated with the long-term prognosis of PCOS. SHBG gene polymorphism is correlated with the risk of PCOS. As SHBG plays a vital role in the occurrence and development of PCOS, knowledge regarding its role in PCOS is helpful for further understanding the molecular mechanism of SHBG in PCOS development and providing new ideas for the treatment of female infertility. Hepatocyte nuclear factor-4α (HNF-4α) is a vital transcription factor in the SHBG synthesis process. HNF-4α binds to the cis-type element DR1 in the SHBG promoter to initiate transcription and regulates hepatic SHBG levels by modulating glucose and lipid metabolism and inflammatory factors. However, it remains unclear whether HNF-4α is indirectly involved in the pathogenesis of PCOS via regulation of hepatic SHBG synthesis. Therefore, this review discusses the interaction between SHBG and the various complications of PCOS as well as the regulatory effect of HNF-4α on SHBG expression.

Nogo­B receptor in relevant carcinoma: Current achievements, challenges and aims (Review).

The novel neurite outgrowth inhibitor B (Nogo­B) receptor (NgBR) is specific for Nogo­B, which is highly expressed in various human organs and cells, including the lung, liver, kidney, smooth muscle cells, blood vessel endothelial cells and inflammatory cells. Previous studies have indicated that NgBR directly interacts with Nogo­B and is able to independently influence lipid and cholesterol homeostasis, angiogenesis, N­glycosylation, the epithelial-mesenchymal transition, the chemotaxis of endothelial cells and cellular proliferation and apoptosis. These multiple functions and actions of this receptor provide an understanding of the important roles of NgBR in various conditions, including fatty liver, atherosclerosis, intracranial microaneurysms, retinitis pigmentosa and severe neurological impairment. Furthermore, NgBR has been demonstrated to exert protean, multifunctional and enigmatic effects in cancer. The present review summarizes the latest knowledge on the suppressing and activating effects of NgBR, emphasizing its function in cancer. Further basic and medical research on this receptor may provide novel insight into its clinical implications on the prognosis of relevant human cancer types.

Neurite Outgrowth Inhibitor B Receptor: A Versatile Receptor with Multiple Functions and Actions.

Members of the reticulon protein family are predominantly distributed within the endoplasmic reticulum. The neurite outgrowth inhibitor (Nogo) has three subtypes, including Nogo-A (200 kDa), Nogo-B (55 kDa), and Nogo-C (25 kDa). Nogo-A and Nogo-C are potent Nogos that are predominantly expressed in the central nervous system. Nogo-B, the splice variant of reticulon-4, is expressed widely in multiple human organ systems, including the liver, lung, kidney, blood vessels, and inflammatory cells. Moreover, the Nogo-B receptor (NgBR) can interact with Nogo-B and can independently affect nervous system regeneration, the chemotaxis of endothelial cells, proliferation, and apoptosis. In recent years, it has been demonstrated that NgBR plays an important role in human pathophysiological processes, including lipid metabolism, angiogenesis, N-glycosylation, cell apoptosis, chemoresistance in human hepatocellular carcinoma, and epithelial-mesenchymal transition. The pathophysiologic effects of NgBR have garnered increased attention, and the detection and enhancement of NgBR expression may be a novel approach to monitor the development and to improve the prognosis of relevant human clinical diseases.

Association between interleukin-17 gene polymorphisms and risk of coronary artery disease.

We conducted a case-control study to estimate the association between IL-17A rs2275913, rs3819025 and rs3748067 polymorphisms and development of coronary artery disease. A total of 415 patients with coronary artery disease and 448 health controls were recruited during the period of March 2013 and October 2014. Genotyping of IL-17A rs2275913, rs3819025 and rs3748067 were analyzed by polymerase chain reaction coupled with restriction fragment length polymorphism. By logistic regression analysis, we found that individuals with the AA genotype (OR, 2.18; 95% CI, 1.35-3.56) and the GA+AA genotype (OR, 1.39, 95% CI, 1.06-1.84) of rs2275913 were associated with an increased risk of coronary artery disease when compared with the GG genotype. Individuals carrying the GA+AA genotype of rs2275913 were more likely to have a higher risk of coronary artery disease in those with hypertension and smoking habit, and the adjusted ORs (95% CI) were 3.92 (2.13-6.82) and 2.74 (1.71-4.40). In conclusion, we suggest that individuals with the AA genotype and the GA+AA genotype of rs2275913 are associated with an increased risk of coronary artery disease, especially in those with hypertension and smoking habit.

Association of LIG4 and XRCC4 gene polymorphisms with the risk of human glioma in a Chinese population.

We conducted a case-control study to assess the LIG4 and XRCC4 genes polymorphisms and development of glioma. A case-control study including 162 glioma cases and 324 controls was conducted in a Chinese population. Genotypes of rs10131 and rs1805388 in LIG4 and rs2075685 and rs1805377 in XRCC4 were conducted by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assay. Conditional logistic regression analysis showed that subjects carrying AA genotype of LIG4 rs10131 was associated with increased risk of glioma when compared with GG genotype, and the OR (95% CI) was 3.26 (1.50-7.23). We found that GA+AA of LIG4 rs10131 was associated with increased risk of glioma in those without family history of cancer, and the OR (95% CI) was 1.78 (1.12-2.83). However, no association was found between variants of LIG4 rs1805388, XRCC4 rs2075685 and XRCC4 rs1805377 and development of glioma. In conclusion, our results suggest that LIG4 rs10131 polymorphism in the DNA repair pathways plays an important role in the risk of glioma in a Chinese population.

Chemical constituents from the fibrous root of Ophiopogon japonicus, and their effect on tube formation in human myocardial microvascular endothelial cells.

In an effort to identify novel active constituents on the cardiovascular system, a systematic study on macroporous resin adsorption of extracts from the fibrous root of Ophiopogon japonicus was performed in a human myocardial microvascular endothelial cell line (HMMEC) based assay. One novel spirostan, named ophiogenin (1), together with six known spirostans (4-8, 10), and one new sesquiterpene glycoside, named ophioside A (2), together with one known monoterpene glycoside (9) were isolated from the active fractions, and the aglycone of compound 2 that was a new natural compound was obtained from the acid hydrolysis of 2, named ophiopogonol (3). Their structures were determined by spectral and chemical analyses. Furthermore, their effect on HMMEC tube formation was also determined. Our results indicated that compounds 4 and 8 could significantly improve the tube formation and 2 showed moderate increasing effect, while compound 5 exhibited potent inhibitory effect.

2-, 3-, and 4-(1-Oxo-1H-2,3-dihydroisoindol-2-yl)benzoic acids and their corresponding organotin carboxylates: synthesis, characterization, fluorescent, and biological activities.

Three novel organotin complexes with general formula Sn(OH)(bz)(2)L (bz = benzyl, HL = 2-, 3-, or 4-(1-oxo-1H-2,3-dihydroisoindol-2-yl)benzoic acid) and one of their ligands were prepared and characterized. In vitro antifungal and antibacterial activities of these complexes and ligands were investigated with the representative strains of Candida albicans, Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. Their fluorescence properties have also been discussed.

cis-Dichloridobis(1,10-phenanthroline)cobalt(II) dimethyl-formamide solvate.

In the title complex, [CoCl(2)(C(12)H(8)N(2))(2)]·C(3)H(7)NO, which has twofold rotation symmetry, the Co(II) cation is coordinated by two 1,10-phenanthroline (phen) mol-ecules and two chloride ligands in a distorted octa-hedral geometry. In the crystal structure, a cavity is created by six complex mol-ecules connected by C-H⋯π inter-actions and non-classical C-H⋯Cl hydrogen bonds. The cavities are occupied by the disordered dimethyl-formamide solvent mol-ecule. The C and N atoms of the C-N bond in the solvent mol-ecule also lie on a crystallographic twofold rotation axis; the remaining atoms of the solvent are statistically disordered (ratio 0.5:0.5) about this axis.

Sexual differences of the inhibitory effect of ethanol on gastrointestinal motility: in vivo and in vitro studies.

Female brain is more sensitive to the acute exposure of ethanol. This study aimed to investigate the sexual difference of the ethanol-induced inhibition of gastrointestinal motility. Wistar rats were fasted and allowed drinking water only 12 - 18 h before the experiments. In the in vivo experiments, by using an oral radiochromium motility marker, the liquid gastric emptying and intestinal transit were [corrected] measured 30 min after ethanol treatment. In the in vitro study, strips of stomach and duodenum smooth muscle were suspended in organ baths containing Krebs solution, and their isometric contractions were also examined. Systemic administration of ethanol (2 g/kg, i.p.) significantly inhibited the gastric emptying and intestinal transit, and the effect on female rats turned out to be greater than that on the male rats (P < 0.05). In an in vitro study, ethanol (0.38 x 10(-3) M - 1.34 x 10(-3) M) inhibited the motility of gastric antrum and duodenum in rats of both sexes, but there was no sexual difference in the inhibitory effect of ethanol on muscle strips. We concluded that sexual difference of the ethanol-induced inhibition of gastrointestinal motility was not resulted from the smooth muscle itself.

[Influence of acupunction on NT-4 expression in spared root ganglion and spinal cord].

OBJECTIVE: To explore the changes of the expression of NT-4 in spared dorsal root ganglia (DRG,L6) on both the operation/Acup side and the nonoperation/non-Acup side as well as in the spinal lamina II (L3, L5, L6) and Clarke' nucleus (L3) of the normal adult cats, partial dorsal rhizotomy cats, and Acup spared DRG cats so as to disclose the relation between NT-4 and the plasticity of spinal cord as well as the Acup promoting spinal cord plasticity. METHODS: Twenty-five adult cats were divided into 5 groups; normal control group; unilateral partial root rhizotomy 7 d and 14 d groups (unilateral L1-L5, L7-S2 DRG were transected, but L6 DRG was spared); Acup spared DRG 7 d and 14 d groups (electro-needle stimulation was performed following unilateral partial root rhizotomy). The cats survived for 7 or 14 days after operation respectively. Bilateral L6 dorsal root ganglia and L3, L5, L6 spinal cord of every group were made into 20 microm frozen sections. Then, sections were stained under the same condition using specific NT-4 (1 : 200) antibody by the immunohistochemistry ABC method. The distribution and the number of NT-4 immunoreactive neurons in bilateral spared DRG (L6) on the operation/Acup side and the nonoperation/Acup side as well as in the, spinal lamina II (L3, L5, L6) and Clarke' nucleus (L3) of each cat were oberserved and counted. All data were analyzed by one-way ANOVA, SNK-q test and paired-t test. RESULTS: Partial dorsal root rhizotomy led to continuous declination of total NT-4 immunoreactive neurons in spared ganglia, till the 14 d, while Acup reversed this tendency and made NT-4 immunoreactive neurons decrease firstly and then approach to normal level till the 14 d after Acup. In addition, Acup increased NT-4 expression in L5, L6 spinal lamina II. CONCLUSION: The above finding indicate that NT-4 plays an important role in the mechanism by which Acup promotes spinal cord plasticity. Partial dorsal root rhizotomy and Acup spared DRG may exert effects on the expression of NT-4 in the/non-operrtion non-Acup side of DRG.

[Partial dorsal root rhizotomy increases the anterograde transportation of neunotrophic factors in primary sensory neuron].

OBJECTIVE: To investigate whether partial dorsal root rhizotomy promotes the anterograde Five adult cats were transportation of BDNF, NT-3 and GDNF in the primary sensory neuron. METHODS: Subjected to unilateral spared root rhizotomy (the DRGs of L1-L5 and L7-S2 were removed, but L6 DRG was spared) and bilateral dorsal roots of L6 were ligated at the same time. Three days after operation, dorsal roots were taken out and made into frozen sections 20 microm in thickness. The sections were stained using specific BDNF, NT-3, GDNF antibody (1:1500) by ABC method. The immunoreactive density was observed in a site near DRG and a site near spinal cord. RESULTS: In the control group (with spared L6 DRG), there were no marked differences in NT-3 and GDNF immunoreactivity between the site near DRG and the site near spinal cord, while BDNF immunoreactivity was more intense in the site near DRG than that in the site near spinal cord. In the operation group, the immunoreactivity of each neurotrophin in the site near DRG was stronger than that in the site near spinal cord, and the immunoreactivities of BDNF, NT-3, GDNF in the site near DRG of the operation were stronger than those of the control group respectively. CONCLUSION: The increasing of immunoreactivities of neurotrophins near DRG following partial dorsal root rhizotomy suggests that partial dorsal root rhizotomy can promote their anterograde transportation from spared DRG to the spinal cord.

[The changes of NT-4 expression in spared root ganglion and spinal cord following partial dorsal root rhizotomy].

OBJECTIVE: This study was conducted to detect the expression levels of NT-4 in the spared dorsal root ganglia (DRG, L6) on the operated side and un-operated side, in the spinal lamina II (L3, L5, L6) and Clarke's nucleus (L3) of the normal adult cats and the cats submitted to partial dorsal rhizotomy. The aim was to illuminate the temporospatial changes of NT-4 expression and its possible relation to spinal cord plasticity. METHODS: Fifteen male adult cats were divided into three groups. The cats of two groups were submitted to unilateral partial dorsal root rhizotomy (L1-L5, L7-S2 DRG were sectioned, but L6 was spared) and animals were sacrificed at survived 7 days and 14 days after operation. The sections were stained by the immunohistochemistry ABC method under the same condition, using NT-4 (1:200, Santa Cruz) antibody. The distribution and the number of NT-4 positive neurons in bilateral spared DRG (L6) in the operated/un-operated side, spinal lamina II (L3, L5, L6) and Clarke's nucleus (L3) of each animal were observed and counted. All data were analyzed by one-way ANOVA, SNK-q test and paired-t test. RESULTS: (1) Seven days after partial dorsal root rhizotomy, the number of NT-4 positive neurons in spared DRG in the operated side was significantly less than that of normal group (P<0.05), but significantly more than that of L6 DRG in the unoperated side (P<0.05); the number of NT-4 positive neurons of L6 DRG on the 14th day after partial dorsal root rhizotomy was also less than that of normal group, 7-day group, and the un-operated side (P<0.05). (2) There was no difference in respect to the number of NT-4 positive neuron in L3, L5, L6 spinal lamina II and L3 Clarke's nucleus in the operated side between the normal group, 7-day operation group and 14-day operation group (P>0.05). CONCLUSION: Our results suggest that partial dorsal root rhizotomy can mainly lead to the change of NT-4 expression in the spared root ganglion, and NT-4 in the unoperated side DRG are involved in spinal cord plasticity.

Interaction and relationship between angiotensin converting enzyme gene and environmental factors predisposing to essential hypertension in Mongolian population of China.

OBJECTIVE: To investigate the association of specific functional gene ACE (I/D) variants of the renin-angiotensin system with essential hypertension (EH) and interaction between ACE (I/D) gene and risk factors for EH in a genetically homogenous Mongolia rural population of China. METHODS: Individuals (n=1099) were recruited from general population of Kezuohouqi Banner in Inner Mongolian Autonomous Region. RESULTS: The association was found between ACE genotype DD plus ID and EH, with an interaction between ACE genotype DD plus ID and cigarette smoking in an additive model. Cigarette smoking index and ACE gene showed a low exposure-gene (LEG) effect on EH, with interaction indices from 7.10 to 1.16. Interaction between ACE genotype DD plus ID and alcohol drinking on EH appeared an additive model. Alcohol drinking index and ACE gene showed a low exposure-gene (LEG) effect on EH, with interaction indices from 1.66 to 1.09. BMI and ACE gene showed a low exposure-gene (LEG) effect on EH, with interaction indices from 6.15 to 2.49. Interactions between ACE genotype and WHR on EH showed a multiplicative model. In a short,there was an interaction between ACE gene and cigarette smoking, alcohol drinking and BMI on EH, especially in a low dose-exposure effect CONCLUSION: It is important for individuals who carry ACE D allele gene to prevent EH, and furthermore, to prevent and control coronary heart disease, in a view of population-based prevention.