CHEMICAL MODIFICATION AND BIOLOGICAL ACTIVITY EXPLORATION OF THE NATURAL PRODUCT-GOSSYPOL

Gossypol is a naturally occurring, highly colored yellow pigment indigenous to the small intercellular pigment glands of the cotton plant genus Gossypium, which is proposed to be part of plant\u27s defense system. Gossypol is characterized by wide contraceptive, antiviral, anticancer and antifungal properties. However, the relatively high toxicity of gossypol precludes its application in medical therapy. For this reason the syntheses and tests of gossypol derivatives, have been tried to enable their application as drugs. In our study, gossypol based methylation, glycosylation and nanoconjugate reactions were explored. The gossypol derivatives were all fully characterized by NMR, MS, FT-IR, UV spectrometry, HPLC and X-ray crystallography. Firstly, hexamethyl ethers of gossypol were synthesized, particularly, existence of four tautomers of gossypol tetramethyl ethers were chromatographically separated and confirmed. Gossypol exhibited the strongest antioxidant activity, while its ethers only remained partial antioxidant activity due to their conjugated naphthalene structure preserved in the derivatives. The result of alpha-amylase inhibitory activities of gossypol and its methylated ethers showed that the gossypol\u27s methylated ethers were the alpha-amylase inhibitors, while gossypol was the alpha-amylase activator. Furthermore, it was found that anticancer activity of the gossypol and its methylated ethers depended on the degree of methylation level of gossypol. Secondly, novel glycosidic gossypol analogues were obtained by the ultrasound-assisted reaction of potassium salt of gossypol with 3, 4, 6-tetra-O-acetyl-α-D-glucopyranosyl bromide under phase transfer catalytic condition. The evaluation of anticancer, antitrypanosomal activities as well as cytotoxicity of those novel glycosidic gossypol derivatives implied that 6, 7\u27-gossypol diglycosidic tetraacetate (compound 8) could be developed into a potential pharmaceutical candidate in the treatment of cancer since it exhibited powerful cancer cells inhibition with significantly low cytotoxicity. In addition, 7, 7\u27-gossypol diglycosidic tetraacetate (compound 7) and 6, 7\u27- gossypol diglycosidic tetraacetate (compound 8) possess antitrypanosomal activity with LD50 value of 2.12 and 2.44 µM, respectively. Finally, gossypol reacted with fullerene [60] in the presence of sarcosine through the Prato reaction, resulting in some unexpected N-methylfulleropyrrolidines, and different products in variable yields were obtained when choosing toluene or chlorobenzene as reaction medium. During the reaction, gossypol decomposed into benzaldehyde which was successfully detected as a new intermediate. In an in vitro assay of NO radical induced apoptosis in 3T3L1 cells for the N-methyl-2, 2-dimethylfulleropyrrolidine (compound 14) showed dose dependent and stronger radical scavenging activities than the parent fullerene

A Network DEA Model with Super Efficiency and Undesirable Outputs: An Application to Bank Efficiency in China

There are two typical subprocesses in bank production—deposit generation and loan generation. Aiming to open the black box of input-output production of banks and provide comprehensive and accurate assessment on the efficiency of each stage, this paper proposes a two-stage network model with bad outputs and supper efficiency (US-NSBM). Empirical comparisons show that the US-NSBM may be promising and practical for taking the nonperforming loans into account and being able to rank all samples. Applying it to measure the efficiency of Chinese commercial banks from 2008 to 2012, this paper explores the characteristics of overall and divisional efficiency, as well as the determinants of them. Some interesting results are discovered. The polarization of efficiency occurs in the bank level and deposit generation, yet does not in the loan generation. Five hypotheses work as expected in the bank level, but not all of them are supported in the stage level. Our results extend and complement some earlier empirical publications in the bank level

Analysis of Chemical Constituents Changing in Physical Process and Nutritional Components of Malus halliana

This study aimed to establish a HPLC method for simultaneous determination of the changing of quercitrin, 3-hydroxyphloridzin, and phloridzin in physical process of M. halliana tea. Meanwhile, the nutritional compositions were determined, using anthrone-sulfuric acid colorimetry and direct titration determination of total sugar and reducing sugar, respectively, in order to provide theoretical basis for quality control and tea production. The results showed that the regression equations for quercitrin, 3-hydroxyphloridzin, and phloridzin were linear in the range of 0.0972–12.15 μg (r=0.999 8), 0.0932~11.65 μg (r=0.999 1), and 0.9~112.5 μg (r=0.999 6), respectively. The average recoveries ranged from 98.19% to 99.35%. The contents of crude protein and the crude fat were measured by spectrophotometric detection and soxhlet extraction detection, respectively. The contents of total sugar, reducing sugar, the fat, and protein were 6.8 g/100 g, 8.5 mg/100 g, 2.399 g/100 g, and 4.362 g/100 g, respectively, in M. halliana tea

In vitro study on human cytomegalovirus affecting early pregnancy villous EVT's invasion function

<p>Abstract</p> <p>Background</p> <p>Human cytomegalovirus (HCMV) is the most common pathogen in uterus during pregnancy, which may lead to some serious results such as miscarriage, stillbirth, cerebellar malformation, fetus developmental retardation, but its pathogenesis has not been fully explained. The hypofunction of extravillous cytotrophoblast (EVT) invasion is the essential pathologic base of some complications of pregnancy. c-erbB-2 is a kind of oncogene protein and closely linked with embryogenesis, tissue repair and regeneration. Matrix metalloproteinase (MMP) is one of the key enzymes which affect EVT migration and invasion function. The expression level changes of c-erbB-2, MMP-2 and MMP-9 can reflect the changes of EVT invasion function.</p> <p>Results</p> <p>To explore the influence of HCMV on the invasion function of EVT, we tested the protein expression level changes of c-erbB-2, MMP-2 and MMP-9 in villous explant cultured in vitro infected by HCMV, with the use of immunohistochemistry SP method and western blot. We confirmed that HCMV can reproduce and spread in early pregnancy villus; c-erbB-2 protein mainly expressed in normal early pregnancy villous syncytiotrophoblast (ST) remote plasma membrane and EVT, especially remote EVT cell membrane in villous stem cell column, little expressed in ST proximal end cell membrane and interstitial cells; MMP-2 protein primarily expressed in early pregnancy villous EVT endochylema and rarely in villous trophoblast (VT), ST and interstitial cells; MMP-9 protein largely expressed in early pregnancy villous mesenchyme, EVT and VT endochylema. Compared with control group, the three kinds of protein expression level in early pregnancy villus of virus group significantly decreased (P < 0.05).</p> <p>Conclusion</p> <p>HCMV can infect villus in vitro and cause the decrease of early pregnancy villous EVT's invasion function.</p

Secure Computation for G-Module and its Applications

Secure computation enables two or more parties to jointly evaluate a function without revealing to each other their private input. G-module is an abelian group M, where the group G acts compatibly with the abelian group structure on M. In this work, we present several secure computation protocols for G-module operations in the online/offline mode. We then show how to instantiate those protocols to implement many widely used secure computation primitives in privacy-preserving machine learning and data mining, such as oblivious cyclic shift, one-round shared OT, oblivious permutation, oblivious shuffle, secure comparison, oblivious selection, DReLU, and ReLU, etc. All the proposed protocols are constant-round, and they are 2X - 10X more efficient than the-state-of-the-art constant-round protocols in terms of communication complexity

Murine model for congenital CMV infection and hearing impairment

<p>Abstract</p> <p>Background</p> <p>Congenital cytomegalovirus (CMV) infection is the leading cause of sensorineural hearing loss (SNHL), and SNHL is the most frequent sequela of congenital CMV infection. But the pathogenic mechanism remains unknown, and there is no ideal CMV intrauterine infection animal model to study the mechanisms by which SNHL develops.</p> <p>Methods</p> <p>We established the congenital murine cytomegalovirus (MCMV) infection model by directly injecting the virus into the placenta on day 12.5 of gestation. Then, we observed the development and the MCMV congenital infection rate of the fetuses on the day they were born. Furthermore, we detected the auditory functions, the conditions of the MCMV infection, and the histological change of the inner ears of 28-day-old and 70-day-old offspring.</p> <p>Results</p> <p>Both the fetal loss rate and the teratism rate of offspring whose placentas were inoculated with MCMV increased, and their body length, head circumference, and weight decreased. The hearing level of offspring both decreased at both 28- and 70-days post birth; the 70-day-old mice developed lower hearing levels than did the 28-day old mice. No significant inflammatory changes in the cochleae of the mice were observed. MCMV DNA signals were mainly detected in the spiral ganglion neurons and the endolymph area, but not in the perilymph area. The number of neurons decreased, and their ultrastructures changed. Moreover, with age, the number of neurons dramatically decreased, and the ultrastructural lesions of neurons became much more severe.</p> <p>Conclusions</p> <p>The results suggest that the direct injection of MCMV into the placenta may efficiently cause fetal infection and disturb the intrauterine development of the fetus, and placental inoculation itself has no obvious adverse effects on offspring. The reduction in the number of spiral ganglion neurons and the ultrastructural lesions of the neurons may be the major cause of congenital CMV infection-induced progressive SNHL.</p

Optimized electroacupuncture treatment for female stress urinary incontinence: study protocol for a multi-center randomized controlled trial

BackgroundStress urinary incontinence (SUI) is a common condition that can severely affect women’s life quality. Electroacupuncture (EA) has been proved to be an optional treatment for SUI, but the tolerance of EA becomes a factor affecting efficiency, which should not be ignored and needs to be solved urgently. The purpose of this study is to find out whether the use of alternating acupoints combination can solve this problem or not and provide an optimization of EA treatment for female SUI.MethodsThis multi-center randomized controlled trial will enroll 360 patients with SUI. They will be randomly assigned to one of the three groups—sacral acupoints group (sacral group), abdominal acupoints group (abdominal group), or alternating acupoints group (alternating group)—at a 1:1:1 ratio. The patients will receive 18 sessions of EA treatment and will be followed up for 48 weeks after the treatment. The primary outcome measure of the study is the change of urine leakage at week 6. The secondary outcomes include the incontinence episode frequency (IEF), International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF), severity of SUI, patient self-evaluation of therapeutic effects, weekly usage of urine pads, ultrasonography of pelvic floor, specialty therapies for SUI, evaluation of discomfort during EA treatment, patient acceptability evaluation and adverse events related to intervention.DiscussionThis trial is specifically designed to offer an optimized EA treatment for female SUI, aiming to enhance their quality of life.Clinical trial registration: ClinicalTrials.gov, identifier ID:NCT05635669