Synthesis of Spirooxindole-1,2-oxazinan-5-ones through 2,2,2-Trifluoroethanol Promoted [3 + 3] Cycloaddition of N-Vinyl Oxindole Nitrones and Oxyallyl Cations.

A variety of spirooxindole-1,2-oxazinan-5-one derivatives were prepared in moderate to excellent yields through 2,2,2-trifluoroethanol (TFE)-promoted [3 + 3] cycloaddition of N-vinyl oxindole nitrones with oxyallyl cations generated from α-tosyloxy ketones under mild reaction conditions. Mechanistic studies revealed that [3 + 3] cycloaddition might involve two possible reaction pathways, including direct [3 + 3] cycloaddition of N-vinyl oxindole ntirones with oxyallyl cations, or the addition of TFE to N-vinyl oxindole nitrones, sequential addition to oxyallyl cations, elimination, and cyclization. The present method features mild reaction conditions, broad substrate scope, good functional group tolerance, easy gram scalable preparation, and new applications of TFE.

Comparing the outcomes and effectiveness of robotic-assisted sacrocolpopexy and laparoscopic sacrocolpopexy in the treatment of pelvic organ prolapse.

INTRODUCTION AND HYPOTHESIS: Abdominal sacrocolpopexy is regarded as the gold standard for management of pelvic organ prolapse (POP). Nowadays, minimally invasive surgeries are preferred, and sacrocolpopexy can be performed using either a laparoscopic or robotic-assisted approach. The aim of the current study was to compare the efficacy and safety of robotic-assisted sacrocolpopexy (RASC) and laparoscopic sacrocolpopexy (LSC) through an updated systematic review and meta-analysis. METHODS: We performed a systematic literature review of different databases and related references from their inception until July 2020 without language restrictions. All randomized control trials and comparative studies that compared RASC and LSC for the management of POP were included. RESULTS: A total of 13 studies including 2115 participants were included for the pooled analysis. The pooled results revealed that RASC was associated with a significantly longer operative time (weighted mean difference, 29.53 min; 95% confidence interval [CI], 12.88 to 46.18 min, P = 0.0005), significantly less estimated blood loss (weighted mean difference, -86.52 ml; 95% CI -130.26 to -42.79 ml, P = 0.0001), significantly fewer overall intraoperative complications (odds ratio [OR] 0.6; 95% CI 0.40 to 0.91; P = 0.01) and significantly lower conversion rate (OR 0.39; 95% CI 0.19 to 0.82; P = 0.01) compared with LSC. There were no significant differences between the length of hospital stays, overall postoperative complications, postoperative stress incontinence, mesh erosion and effectiveness between the two groups. CONCLUSION: The current study showed comparable efficacy between RASC and LSC. Though RASC was associated with less blood loss and a lower conversion rate, the differences were not clinically significant. The choice of surgical procedure with either RASC or LSC is according to surgeon discretion and patient preferences.

Synthesis of α-aminooxy amides through [3 + 3] cycloaddition and Sc(OTf)3-catalyzed double C-N bond cleavage in a one-pot reaction.

Various α-aminooxy amides bearing a quaternary carbon at the α-position were prepared in good to excellent yields under mild reaction conditions from N-vinyl nitrones and α-bromohydroxamates. The N-vinyl nitrones tolerate a wide range of N-vinyl fluorenone nitrones and N-vinyl isatin nitrones. Mechanistic studies show that the reaction initially proceeds through [3 + 3] cycloaddition between N-vinyl nitrones and aza-oxyallyl cations generated from α-bromohydroxamates to afford six-membered N,O-heterocycles, followed by double C-N bond cleavage in the presence of the Sc(OTf)3 catalyst. A selective N-O bond cleavage of the obtained α-aminooxy amides is also realized under Fe/NH4Cl conditions. Furthermore, gram-scalable preparations of α-aminooxy amides are easily achieved.

Dezocine Alleviates Morphine-Induced Dependence in Rats.

BACKGROUND: Opioid dependence is a major public health issue without optimal therapeutics. This study investigates the potential therapeutic effect of dezocine, a nonaddictive opioid, in opioid dependence in rat models. METHODS: Dezocine was administered intraperitoneally to a morphine-dependent rat model to investigate its effect on withdrawal and conditioned place preference (CPP). Effect of dezocine on morphine withdrawal syndrome and CPP was analyzed using 2-way analysis of variance (ANOVA) followed by Tukey's post hoc test. Buprenorphine and vehicle solution containing 20% (v/v) dimethyl sulfoxide were used for positive and negative control, respectively. The astrocytes activation in nucleus accumbens was assessed by immunofluorescence assay of glial fibrillary acidic protein. Effect of dezocine and buprenorphine on the internalization of κ opioid receptor (KOR) was investigated using Neuro2A expressing KOR fused to red fluorescent protein tdTomato (KOR-tdT). Buprenorphine and dezocine were screened against 44 G-protein-coupled receptors, ion channels, and transporter proteins using radioligand-binding assay to compare the molecular targets. RESULTS: The mean withdrawal score was reduced in rats treated with 1.25 mg·kg dezocine compared to vehicle-treated control animals starting from the day 1 (mean difference: 7.8; 95% confidence interval [CI], 6.35-9.25; P < .0001 by 2-way ANOVA). Significance was observed at all treatment days, including day 7 (mean difference: 2.13; 95% CI, 0.68-3.58; P < .001 by 2-way ANOVA). Furthermore, dezocine inhibited the reinstatement of morphine-induced CPP (mean difference: 314; 95% CI, 197.9-430.1; P < .0001 by 2-way ANOVA) compared to the control group. Chronic morphine administration induced astrocytes activation in nucleus accumbens, which was attenuated by dezocine. Dezocine blocked the agonist-induced KOR internalization in vitro, 1 of the mechanisms involved in the downstream signaling and development of opioid dependence. Dezocine had affinity to norepinephrine and serotonin transporters and sigma-1 receptor, whereas buprenorphine showed no activity against these targets. CONCLUSIONS: Dezocine could potentially be used to alleviate opioid dependence. Due to the unique molecular target profile different from buprenorphine, it might have important value in studying the mechanisms of morphine dependence and developing novel therapeutic approaches.

Evolution of drug-resistant mutations in HBV genomes in patients with treatment failure during the past seven years (2010-2016).

The objective of this study was to analyze the prevalence of drug-resistant HBV mutants in patients with treatment failure during the past seven years (2010-2016). 4055 HBV-infected patients who underwent HBV polymerase gene mutation test from 2010 to 2016 were enrolled. The nucleos(t)ide analogues (NAs) resistance mutation positions, including rtL180, rtA181, rtT184, rtS202, rtM204, rtI233, rtN236, rtI169, rtV173, and rtM250 were analyzed. Genotypic resistance mutations were detected in 30.8% (1248/4055) of the patients with treatment failure. Rates of drug-resistant mutations associated with LAM, ADV, ETV, and multidrug were 27.23% (1104/4055), 9.67% (392/4055), 3.69% (150/4055), and 0.79% (32/4055). Among the primary NA-resistant mutations, rtM204I (13.44%, 545/4055) occurred more frequently, followed by rtM204V, rtN236T, rtA181T, and rtA181V. For single-base mutations, rtL180M and rtA181V increased gradually during the past seven years, while rtM204I/V and rtN236T decreased after 2015. The development of drug-resistant mutations positively correlated with the consumption of ETV (r = 0.964, P = 0.002), and weakly correlated with that of LAM (r = 0.679, P = 0.109) and ADV (r = 0.429, P = 0.354). Moreover, single-base mutation rtA181V and multi-base mutations (rtL180M + M204I and rtL180M + M204V + M204I) were more common in HBV genotype C than those in genotype B (1.94% vs. 0.66%, 1.84% vs. 0.16%, 1.02% vs. 0.16%, respectively). NA-related mutations in HBV RT region increased in the past seven years, especially for LAM. Frequencies of rtL180M and rtA181T/V increased gradually in the past seven years, to which we should pay more attention.

Copper-Catalyzed Selective N-Vinylation of 3-(Hydroxyimino)indolin-2-ones with Alkenyl Boronic Acids: Synthesis of N-Vinyl Nitrones and Spirooxindoles.

A copper-catalyzed selective cross-coupling reaction of 3-(hydroxyimino)indolin-2-ones with alkenyl boronic acids to access (E)-N-vinyl oxindole nitrones has been achieved under mild conditions. The studies showed that catalytic copper salt selectively gave mono N-vinylation products, while 2.0 equiv of copper salt provided double N-vinylation products. The control experiments revealed that the carbonyl group in 3-(hydroxyimino)indolin-2-one played important roles on N-vinylation. Furthermore, the prepared N-vinyl oxindole nitrones could be converted to spirooxindoles in good yields under thermal conditions.

Cycloaddition of Fluorenone N-Aryl Nitrones with Methylenecyclopropanes and Sequential 1,3-Rearrangement: An Entry to Synthesis of Spirofluorenylpiperidin-4-ones.

A facile synthesis of various spirofluorenylpiperidin-4-ones has been achieved in good yields from fluorenone N-aryl nitrones and methylenecyclopropanes. This method involved an initial cycloaddition to form a 5-spirocyclopropane-isoxazoline, which underwent a highly selective 1,3-rearrangement to give the desired product. The stereochemistry of the spirofluorenylpiperidin-4-one could be controlled by the cycloaddition and sequential rearrangement strategy. Furthermore, the spirofluorenylpiperidin-4-ones could be not only prepared in one-pot procedure but also converted to useful scaffolds by reduction or oxidation conditions.

Iron(III) and BF3·OEt2-Promoted O-Transfer Reaction of N-Aryl-α,ß-Unsaturated Nitrones to Prepare Difluoroboron ß-Ketoiminates.

We described an iron(III) and BF3·OEt2-promoted oxygen transfer reaction of N-aryl-α,ß-unsaturated nitrones to prepare various N,O-difluoroboron ß-ketoiminates in good yields ranging from 24% to 87%. Control experiments revealed that the enaminone was the vital intermediate for the formation of N,O-difluoroboron ß-ketoiminates, and iron(III) combined with BF3·OEt2 played as cocatalyst to promote the oxygen transfer reaction through intramolecular cyclization and N-O bond cleavage. More importantly, an estrone-derived N,O-difluoroboron ß-ketoiminate was easily prepared in 40% yield from estrone in four steps.

Facile growth of thermochromic VO2 nanostructures with greatly varied phases and morphologies.

We have successfully and reproducibly synthesized a variety of novel vanadium dioxide (VO2) nanostructures, including metastable monoclinic VO2(B) nanoneedles and nanocorals, orthorhombic VO2(O) nanoparticles, and monoclinic VO2(M) nanofacets by manipulating the aging time of a facile sol-gel approach and the subsequent postannealing conditions. We envision that this previously unreported highly controlled synthesis and the resulting distinct morphologies of VO2 will not only provide a promising route for reliably selecting the phase, size, and morphology of these nanostructures, as well as achieving a fundamental understanding of their unusual temperature-dependent optical transmittance, but also facilitate the synthesis of functional VO2 nanostructures for a number of novel applications.

Advances in the study of the structures and bioactivities of metabolites isolated from mangrove-derived fungi in the South China Sea.

Many metabolites with novel structures and biological activities have been isolated from the mangrove fungi in the South China Sea, such as anthracenediones, xyloketals, sesquiterpenoids, chromones, lactones, coumarins and isocoumarin derivatives, xanthones, and peroxides. Some compounds have anticancer, antibacterial, antifungal and antiviral properties, but the biosynthesis of these compounds is still limited. This review summarizes the advances in the study of secondary metabolites from the mangrove-derived fungi in the South China Sea, and their biological activities reported between 2008 and mid-2013.

[Current progress in cryopreservation of small numbers of sperm].

Human sperm cryopreservation is an increasingly mature technique in assisted reproduction. However, conventional sperm cryopreservation is not suitable for the cryopreservation of small numbers of sperm. The solution to the cryopreservation of small numbers of sperm may contribute a lot to the clinical treatment of asthenospermia, oligospermia and azoospermatism. Recently, many researchers focus on searching for appropriate carriers for the cryopreservation of small numbers of sperm. This article outlines the effects of current cryopreservation methods including empty zona pellucida, microdrops, other mocrocarriers, testicular tissue cryopreservation and testicular sperm and epididymal sperm refrigeration.

Interpenetration Networked Polyimide-Epoxy Copolymer under Kinetic and Thermodynamic Control for Anticorrosion Coating.

Epoxy (EP) was copolymerized with polyamic acid (PAA, precursor of polyimide (PI)) with termanil monomers of (1) 4,4'-Oxydianiline (ODA) and (2) pyromellitic dianhydride (PMDA) individually to form (PI-O-EP) and (PI-P-EP) copolymers. The FTIR spectrum of PI-O-EP copolymerization intermediates shows that some amide-EP linkages were formed at low temperature and were broken at higher temperature; in additoin, the released amide was available for subsequent imidization to form PI. The curing and imidization of the amide groups on PAA were determined by reaction temperature (kinetic vs. thermodynamic control). In PI-P-EP, the released amide group was very short-lived (fast imidization) and was not observed on FTIR spectra. Formation and breakage of the amide-EP linkages is the key step for EP homopolymerization and formation of the interpenetration network. PI contributed in improving thermal durability and mechanical strength without compromising EP's adhesion strength. Microphase separations were minimal at PI content less than 10 wt%. The copolymerization reaction in this study followed the "kinetic vs. thermodynamic control" principle. The copolymer has high potential for application in the field of higher-temperature anticorrosion.

Fine valence regulation of hydrated vanadium oxide as a novel cathode for stable potassium-ion storage.

Layered V10O24·nH2O with a large interlayer spacing of 14 Å is hydrothermally synthesized and used as a cathode for potassium-ion batteries. It exhibits a capacity of 110 mA h g-1 with a capacity retention of 99.2% over 700 cycles. Its storage mechanism is identified as pseudo-capacitive intercalation.

Knowledge graph of wastewater-based epidemiology development: A data-driven analysis based on research topics and trends.

Wastewater-based epidemiology (WBE) has contributed significantly to the monitoring of drug use and transmission of viruses that has been published in numerous research papers. In this paper, we used LitStraw, a self-developed text extraction tool, to extract, analyze, and construct knowledge graphs from nearly 900 related papers in PDF format collected in Web of Science from 2000 to 2021 to analyze the research hotspots and development trends of WBE. The results showed a growing number of WBE publications in multidisciplinary cross-collaboration, with more publications and close collaboration between the USA, Australia, China, and European countries. The keywords of illicit drugs and pharmaceuticals still maintain research hotness, but the specific research hotspots change significantly, among which the research hotspots of new psychoactive substances, biomarkers, and stability show an increasing trend. In addition, judging the spread of COVID-19 by the presence of SARS-CoV-2 RNA in sewage has become the focus since 2020. This work can show the development of WBE more clearly by constructing a knowledge graph and also provide new ideas for the paper mining analysis methods in different fields.

Effectiveness of various treatment modalities in children with vesicoureteral reflux grades II-IV: a systematic review and network meta-analysis.

BACKGROUND: Vesicoureteral reflux (VUR) is one of the most common risk factors of urinary tract infection (UTI) among children. Various treatment modalities including antibiotic prophylaxis, surgical or endoscopic corrections and conservative treatment were used depending on the severity of VUR. The aim of this study is to compare the effectiveness of these treatment modalities in children with VUR grades II-IV by conducting a systematic review and network meta-analysis. METHODS: A systematic search from different databases was performed from their earliest records to December 2022 without any language restriction. Only randomised controlled trials were included in this study. Effectiveness of treatment modalities was mainly compared by UTI. Other outcomes for renal scarring and resolution by renal units were also measured between treatments. RESULTS: A total of 11 studies with 1447 children were included in this study. While comparing with antibiotic prophylaxis in network meta-analysis for UTI recurrence, surgical treatment probably lowers the rate of UTI recurrence (Log OR -0.26, 95% CI -0.54 to 0.02, high quality). However, endoscopic treatment (Log OR 0.2, 95% CI -1.41 to 1.81, high quality) and conservative treatment (Log OR 0.15, 95% CI -0.45 to 0.75, high quality) revealed probably inferior to antibiotic treatment. CONCLUSION: Both pairwise and network meta-analytic results probably showed no difference between the treatments in terms of their impact on UTI recurrence, progression of previous renal scars, or formation of new renal scars in children with VUR grades II-IV. These findings may offer a better understanding of each treatment and evidence-based suggestions for the choice of treatment, which should be individualised and based on the patient's risk factors.

Tea polyphenol and epigallocatechin gallate ameliorate hyperlipidemia via regulating liver metabolism and remodeling gut microbiota.

Hyperlipidemia can directly cause metabolic diseases that seriously endanger disorder and metabolism and gut health. Tea polyphenol (TP) and epigallocatechin gallate (EGCG) was found to improve blood lipid levels and gut microbiota. This study aimed to investigate the effects of TP and EGCG on alleviating hyperlipidemia and liver fat accumulation with physiology, genomics, and metabolomics. Results showed that both TP and EGCG reduced body weight, and TP showed advantages in the decrease of serum cholesterol and triglycerides in hyperlipidemic rats induced by the high-fat diet. Moreover, EGCG may protect liver function via reducing the glycerophospholipids increased by high-fat diet intervention. TP remodeled the gut microbiota composition and enriched the abundance of beneficial bacteria (Bacteroides, Faecalibacterium, Parabacteroides, Akkermansia), and EGCG may improve gut health via promoting the acid-producing bacteria (such as Butyricimonas, Desulfovibrio). The above results provided new insights into the hypolipidemic mechanism of TP and EGCG.

The protective effect of Cerebralcare Granule® on brain edema, cerebral microcirculatory disturbance, and neuron injury in a focal cerebral ischemia rat model.

OBJECTIVE: The purpose of the present study was to explore the protective effects of CG on rat cerebral injury after focal cerebral I /R. METHODS: Male Sprague-Dawley rats were subjected to right middle cerebral artery occlusion for 60 minutes followed by reperfusion for 60 minutes or 24 hours. CG (0.4 or 0.8 g/kg) was administrated 90 minutes before ischemia. Brian edema was evaluated by Evan's blue dye extravasations and brain water content, leukocyte adhesion, and albumin leakage were determined with an upright fluorescence microscope, and neuron damage was assessed by 2,3,5-triphenyltetrazolium chloride staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, and immunohistochemistry of caspase-3, p53, p53 upregulated modulator of apoptosis. RESULTS: Focal cerebral I/R elicited a prominent brain edema, an increase in leukocyte adhesion, and albumin leakage, as well as neuron damage. All the insults after focal cerebral I/R were significantly attenuated by pretreatment with CG. CONCLUSIONS: Pretreatment with CG significantly reduced focal cerebral I/R-induced brain edema, cerebral microcirculatory disturbance, and neuron damage, suggesting the potential of CG as a prophylactic strategy for patients in danger of stroke.

Periodic DLC Interlayer-Functionalized Bi-Sb-Te-Based Nanostructures: A Novel Concept for Building Heterogenized Superarchitectures with Enhanced Thermoelectric Performance.

According to the innovative design concept of omnidirectional quasi-order hetero-nanocomposites proposed for potentially realizing high thermoelectric performance, a series of superarchitectures consisting of longitudinally periodic diamond-like carbon (DLC) interlayers in latitudinally well-aligned Bi-Sb-Te (BST)-based nanostructures were successfully demonstrated for the first time using dual-beam pulsed laser deposition. This work confirmed that the periodic appearance of DLC is a practical approach to instantly resetting the BST deposition into another new crystal growth cycle. The optimized Seebeck coefficient of ∼500 µV K-1 and the corresponding power factor of ∼40 µW cm-1 K-2 achieved are comparable to or higher than the reported values for BST or BST-based nanocomposites, which evidently originated from the periodically added DLC, as clarified in the Pisarenko plot. In addition, the DLC additives effectively reduce the thermal transport as qualitatively evidenced by micro-Raman characterizations.

Introducing a Pseudocapacitive Lithium Storage Mechanism into Graphite by Defect Engineering for Fast-Charging Lithium-Ion Batteries.

The extreme fast-charging capability of lithium-ion batteries (LIBs) is very essential for electric vehicles (EVs). However, currently used graphite anode materials cannot satisfy the requirements of fast charging. Herein, we demonstrate that intrinsic lattice defect engineering based on a thermal treatment of graphite in CO2 is an effective method to improve the fast-charging capability of the graphite anode. The activated graphite (AG) exhibits a superior rate capability of 209 mAh g-1 at 10 C (in comparison to 15 mAh g-1 for the pristine graphite), which is attributed to a pseudocapacitive lithium storage behavior. Furthermore, the full cell LiFePO4||AG can achieve SOCs of 82% and 96% within 6 and 15 min, respectively. The intrinsic carbon defect introduced by the CO2 treatment succeeds in improving the kinetics of lithium ion intercalation at the rate-determining step during lithiation, which is identified by the distribution of relaxation times (DRT) and density functional theory (DFT) calculations. Therefore, this study provides a novel strategy for fast-charging LIBs. Moreover, this facile method is also suitable for activating other carbon-based materials.

An updated systematic review and network meta-analysis comparing open, laparoscopic and robotic-assisted sacrocolpopexy for managing pelvic organ prolapse.

Abdominal sacrocolpopexy is considered as the gold standard treatment for pelvic organ prolapse. Sacrocolpopexy can be performed using open (OSC), laparoscopic (LSC), and robotic-assisted (RSC) approaches. The aim of this study is to compare the outcomes between these three approaches for managing pelvic organ prolapse by conducting a systematic review and network meta-analysis. A systematic search was performed in different databases from their earliest records to April 2021 with no restriction on languages. Only randomized controlled trials that compared the outcomes between OSC, LSC, and RSC were included in this study. A total of 6 studies with 486 participants were included in this study. Operative time was significantly shorter in OSC than in RSC and LSC. The probability rank showed less estimated blood loss in RSC and lowest overall postoperative complications in LSC. Probability scores also showed best anatomical outcomes for postoperative points C and Bp in RSC and for point Ba in LSC. Despite significantly longer operative time, RSC and LSC may provide better anatomical outcomes, less estimated blood loss, and less overall postoperative complications than OSC. However, this study did not find significant differences between RSC and LSC in efficacy and safety.