Density functional theory study of mechanism of forming a spiro-Si-heterocyclic ring compound from Me2SiSi: and acetaldehyde

AbstractThe H2SiSi: and its derivatives (X2SiSi:, X=H, Me, F, Cl, Br, Ph, Ar…) is a new species. Its cycloaddition reaction is a new area for the study of silylene chemistry. The mechanism of the cycloaddition reaction between singlet Me2SiSi: and acetaldehyde has been investigated with the B3LYP/6-31G∗ method in article. From the potential energy profile, it could be predicted that the reaction has one dominant reaction pathway. The reaction rule presented is that the two reactants firstly form a four-membered Si-heterocyclic ring silylene through the [2+2] cycloaddition reaction. Because of the 3p unoccupied orbital of Si: atom in the four-membered Si-heterocyclic ring silylene and the π orbital of acetaldehyde forming a π→p donor–acceptor bond, the four-membered Si-heterocyclic ring silylene further combines with acetaldehyde to form an intermediate. Because the Si atom in intermediate happens sp3 hybridization after transition state, then, intermediate isomerizes to a spiro-Si-heterocyclic ring compound via a transition state

Quercetin and Bornyl Acetate Regulate T-Lymphocyte Subsets and INF-γ/IL-4 Ratio In Utero in Pregnant Mice

The objective of this study is to investigate the antiabortive effects of Quercetin and Bornvl Acetate and their immunological modulation at maternal-fetal interface. Lipopolysaccharide (LPS) was injected via tail vein to induce abortion in mice which received Quercetin and Bornvl Acetate at days 4–7 of gestation. Uterine CD4+/CD8+ T lymphocytes and IFN-γ/IL-4 of each group (n = 10) were detected by immunohistochemistry and enzyme-linked immunosorbent assay, respectively. The ratio of CD4+/CD8+ increased significantly (P < .01) in the uterus of LPS-induced abortion mice. In the Quercetin and Bornvl Acetate pretreated mice followed by LPS administration, the ratio of CD4+/CD8+ dropped to 0.562 ± 0.021, lower than that of LPS-abortion group (P < .01). The mean value of IFN-γ/IL-4 in LPS-treated mice was 0.310 ± 0.066, higher than that of Quercetin and Bornyl Acetate group. The results indicate that Quercetin and Bornyl Acetate have an antiabortive effect through modulation of immunological balance at maternal-fetal interface

ADJUVANT EFFECTS OF SIJUNZI DECOCTION IN CHICKENS ORALLY VACCINATED WITH ATTENUATED NEWCASTLE-DISEASE VACCINE

Many Chinese Herbal medicines (CHMs) and their components have been reported to enhance immunity. In this study, the capacity for the Chinese herbal medicine, oral administration Sijunzi Decoction (SJZD) in stimulating Newcastle disease virus(NDV) immunity in chickens was examined. Serum was sampled on days 20,30,40,50 and 60 and tissues were collected on days 20, 40 and 60, respectively. The immune responses were determined by means of hemagglutination inhibition test, immunohistochemistry examination and semi-quantitative RT–PCR. The results showed that SJZD could increase the antibody titers and the area coefficient of IgA secreting cells, promote the expression of IL-2 mRNA in the whole immune period and IFN-γ mRNA was increased in the initial stage. The SJZD used was safe with no adverse effects on chicken weight or survival, providing evidence for the use of SJZD as an oral adjuvant

Acetyl-Coenzyme A Synthetase 2 Potentiates Macropinocytosis and Muscle Wasting Through Metabolic Reprogramming in Pancreatic Cancer

BACKGROUND & AIMS: Rapid deconditioning, also called cachexia, and metabolic reprogramming are two hallmarks of pancreatic cancer. Acetyl-coenzyme A synthetase short-chain family member 2 (ACSS2) is an acetyl-enzyme A synthetase that contributes to lipid synthesis and epigenetic reprogramming. However, the role of ACSS2 on the nonselective macropinocytosis and cancer cachexia in pancreatic cancer remains elusive. In this study, we demonstrate that ACSS2 potentiates macropinocytosis and muscle wasting through metabolic reprogramming in pancreatic cancer. METHODS: Clinical significance of ACSS2 was analyzed using samples from patients with pancreatic cancer. ACSS2-knockout cells were established using the clustered regularly interspaced short palindromic repeats-associated protein 9 system. Single-cell RNA sequencing data from genetically engineered mouse models was analyzed. The macropinocytotic index was evaluated by dextran uptake assay. Chromatin immunoprecipitation assay was performed to validate transcriptional activation. ACSS2-mediated tumor progression and muscle wasting were examined in orthotopic xenograft models. RESULTS: Metabolic stress induced ACSS2 expression, which is associated with worse prognosis in pancreatic cancer. ACSS2 knockout significantly suppressed cell proliferation in 2-dimensional and 3-dimensional models. Macropinocytosis-associated genes are upregulated in tumor tissues and are correlated with worse prognosis. ACSS2 knockout inhibited macropinocytosis. We identified Zrt- and Irt-like protein 4 (ZIP4) as a downstream target of ACSS2, and knockdown of ZIP4 reversed ACSS2-induced macropinocytosis. ACSS2 upregulated ZIP4 through ETV4-mediated transcriptional activation. ZIP4 induces macropinocytosis through cyclic adenosine monophosphate response element-binding protein-activated syndecan 1 (SDC1) and dynamin 2 (DNM2). Meanwhile, ZIP4 drives muscle wasting and cachexia via glycogen synthase kinase-β (GSK3β)-mediated secretion of tumor necrosis factor superfamily member 10 (TRAIL or TNFSF10). ACSS2 knockout attenuated muscle wasting and extended survival in orthotopic mouse models. CONCLUSIONS: ACSS2-mediated metabolic reprogramming activates the ZIP4 pathway, and promotes macropinocytosis via SDC1/DNM2 and drives muscle wasting through the GSK3β/TRAIL axis, which potentially provides additional nutrients for macropinocytosis in pancreatic cancer

Improving the Efficacy of Conventional Therapy by Adding Andrographolide Sulfonate in the Treatment of Severe Hand, Foot, and Mouth Disease: A Randomized Controlled Trial

Background. Herb-derived compound andrographolide sulfonate (called Xiyanping injection) recommended control measure for severe hand, foot, and mouth disease (HFMD) by the Ministry of Health (China) during the 2010 epidemic. However, there is a lack of good quality evidence directly comparing the efficacy of Andrographolide Sulfonate combination therapy with conventional therapy. Methods. 230 patients were randomly assigned to 7–10 days of Andrographolide Sulfonate 5–10 mg/Kg/day and conventional therapy, or conventional therapy alone. Results. The major complications occurred less often after Andrographolide Sulfonate (2.6% versus 12.1%; risk difference [RD], 0.94; 95% CI, 0.28–1.61; P=0.006). Median fever clearance times were 96 hours (CI, 80 to 126) for conventional therapy recipients and 48 hours (CI, 36 to 54) for Andrographolide Sulfonate combination-treated patients (χ2=16.57, P<0.001). The two groups did not differ in terms of HFMD-cause mortality (P=1.00) and duration of hospitalization (P=0.70). There was one death in conventional therapy group. No important adverse event was found in Andrographolide Sulfonate combination therapy group. Conclusions. The addition of Andrographolide Sulfonate to conventional therapy reduced the occurrence of major complications, fever clearance time, and the healing time of typical skin or oral mucosa lesions in children with severe HFMD

GJB2 mutation spectrum in 2063 Chinese patients with nonsyndromic hearing impairment

Background: Mutations in GJB2 are the most common molecular defects responsible for autosomal recessive nonsyndromic hearing impairment (NSHI). The mutation spectra of this gene vary among different ethnic groups. Methods: In order to understand the spectrum and frequency of GJB2 mutations in the Chinese population, the coding region of the GJB2 gene from 2063 unrelated patients with NSHI was PCR amplified and sequenced. Results: A total of 23 pathogenic mutations were identified. Among them, five (p.W3X, c.99delT, c.155_c.158delTCTG, c.512_c.513insAACG, and p.Y152X) are novel. Three hundred and seven patients carry two confirmed pathogenic mutations, including 178 homozygotes and 129 compound heterozygotes. One hundred twenty five patients carry only one mutant allele. Thus, GJB2 mutations account for 17.9% of the mutant alleles in 2063 NSHI patients. Overall, 92.6% (684/739) of the pathogenic mutations are frame-shift truncation or nonsense mutations. The four prevalent mutations; c.235delC, c.299_c.300delAT, c.176_c.191del16, and c.35delG, account for 88.0% of all mutantalleles identified. The frequency of GJB2 mutations (alleles) varies from 4% to 30.4% among different regions of China. It also varies among different sub-ethnic groups. Conclusion: In some regions of China, testing of the three most common mutations can identify at least one GJB2 mutant allele in all patients. In other regions such as Tibet, the three most common mutations account for only 16% the GJB2 mutant alleles. Thus, in this region, sequencing of GJB2 would be recommended. In addition, the etiology of more than 80% of the mutant alleles for NSHI in China remains to be identified. Analysis of other NSHI related genes will be necessary

An ab initio study of the mechanism of formation of a silicic bis-heterocyclic compound from silylenesilylene (H2Si=Si:) and ethene

The mechanism of the cycloaddition reaction between singlet state silylenesilylene (H2Si=Si:) and ethene in which a silicic bisheterocyclic compound is formed was investigated using the CCSD(T)//MP2/6-31

Effects of Huangqi Maxingshigan decoction on infectious laryngotracheitis in chickens

This study was conducted to investigate the effectiveness and possible mechanisms of an herbal prescription, <em>Huangqi Maxingshigan</em> decoction (R<em>adix Astragali, Herba Ephedrae, Almond, Gypsum Fibrosum, Radix Glycytthizae</em>) on infectious laryngotracheitis (ILT) in chickens. One hundred and sixty one-day-old chicks were randomly allocated into four groups, housed in isolated cages of 40 birds each: groupⅠwas Huangqi Maxingshigan decoction treatment group, group II as <em>Ding Chuan San</em> control group, group III as the model group, and group IV as the blank control group. Except for the blank control group, other groups were challenged with infectious laryngotracheitis virus via the intratracheal route on age day 52. Birds in group I were administered <em>Huangqi Maxingshigan </em>decoction at a concentration of 0.4 mL, or with <em>Ding Chuan San</em> in group II for comparison at 48 h post virus challenge (day 54) when they showed clinical signs, 2 times daily for 5 days consecutively. Then, the superoxide dismutases (SOD) activity and malondialdehyde (MDA) contents in serum, the expression of IFN-γ, IL-4 mRNA in spleen, the sIgA contents in tracheal fluid, the sIgA secreting cells in trachea were determined on day 5, day 15, day 25 post infection. The results showed that <em>Huangqi Maxingshigan</em> decoction could correct Th2-dominant Th1/th2 imbalance through up-regulation of IFN-γ, and down-regulation of IL-4 at the transcriptional level, enhance cell-mediated immunity, ease inflammatory responses caused by ILTV. The results also showed that <em>Huangqi Maxingshigan </em>decoction provide an important antioxidant defense in the process of anti-ILT. Furthermore, it could induce the production of sIgA to enhance mucosal immunity

Bisphenol A Exposure during Pregnancy Alters the Mortality and Levels of Reproductive Hormones and Genes in Offspring Mice

The present study investigated the reproductive toxicity of bisphenol A (BPA) exposure to the mother on the offspring mice. BPA was given to pregnant mice at 50 mg/kg, 500 mg/kg, and 2500 mg/kg BW BPA daily by gavage during the whole gestation period. The offspring mice were sacrificed at 8 weeks of age. Results showed that exposure of BPA to the mother increased the mortality (P<0.05). Maternal exposure of BPA reduced the levels of T (♂) and FSH (♀) (P<0.01) and elevated E2 (♀) level in the adult offspring (P<0.01). BPA exposure caused testicular damage as shown by less Leydig cells and ovarian injury as shown by more vacuoles and less corpus granules in the adult offspring mice. Immunohistochemistry revealed that maternal exposure of BPA increased Bax and decreased Bcl-2 at the protein levels in testicular and ovary tissues in the offspring mice. BPA significantly reduced the expression of StAR in male offspring (P<0.05). Interestingly, the mRNA levels of Cyp11a were significantly decreased in 50 mg/kg groups and were increased in 500 mg/kg group in the males. Reduced Kitlg and elevated Amh at the mRNA levels were detected in the female offspring