Electrophotocatalytic Tellurosulfonylation of Alkynes for the Synthesis of ß-(Telluro)vinyl Sulfones.

Difunctionalization of alkynes has gained a lot of interest in current organic chemistry. Herein, we developed an electrophotocatalytic multicomponent cascade reaction of alkynes and indoles with sulfinic acid sodium salts using elemental tellurium as the tellurium source. Using synergistic anodic oxidation and visible-light irradiation, various ß-(telluro)vinyl sulfones have been prepared. This strategy features mild reaction conditions, excellent substrate scope, readily available starting materials, and great functional group tolerance.

Impaired Indole Acetic Acid and Reduced Indole-Producing Bacteria Contribute to Swainsonine-Induced Liver Inflammation.

Liver inflammation could be elicited by swainsonine in livestock, affecting the development of agriculture and animal husbandry. Our previous study showed an important role of bile acids (BAs) in swainsonine-induced hepatic inflammation. However, its pathogenesis, particularly the roles of a comprehensive profile of liver and serum metabolites and microbial-derived indole metabolites, has not been clarified. This study aimed to demonstrate the mechanisms linking the indole-producing bacteria and indole metabolites to swainsonine-induced hepatic inflammation by combining Targeted 500 metabolomics and quantitative analysis of indole metabolites. Swainsonine significantly disturbed the liver and serum metabolomes in mice. Genus Akkermansia alleviating inflammation and genus Lactobacillus producing indole metabolites were significantly declined. Indole acetic acid (IAA) was the only reduced aryl hydrocarbon receptor (AHR) ligand in this study. Analogously, some bacteria causing liver damage markedly increased. These findings suggested that indole-producing bacteria and indole metabolites may be potential triggers of swainsonine-induced hepatic inflammation.

Antisense oligodeoxynucleotides against dynamin-related protein 1 reduce remifentanil-induced hyperalgesia by modulating spinal N-methyl-D-aspartate receptor expression in rats.

Background: Spinal N-methyl-D-aspartate (NMDA) receptor activation is attributed to remifentanil-induced hyperalgesia (RIH). However, the specific mechanism and subsequent treatment is still unknown. Previous studies have shown that the dynamin-related protein 1 (DRP1)-mitochondria-reactive oxygen species (ROS) pathway plays an important role in neuropathic pain. This study examined whether antisense oligodeoxynucleotides against DRP1 (AS-DRP1) could reverse RIH. Methods: The authors first measured changes in paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) at 24 hours before remifentanil infusion and 4, 8, 24, and 48 hours after infusion. The expression levels of DRP1 and NR2B were measured after behavioral testing using Western blotting. In addition, DRP1 expression was knocked down by intrathecal administration of AS-DRP1 to investigate the effects of DRP1 on RIH. The behavioral testing, the expression levels of spinal DRP1 and NR2B, and dorsal mitochondrial superoxide were measured. Changes in mitochondrial morphology were assessed using electron microscopy. Results: After remifentanil exposure, upregulation of spinal DRP1 and NR2B was observed along with a reduction in PWMT and PWTL. In addition, AS-DRP1 improved RIH-induced PWTL and PWMT (P < 0.001 and P < 0.001) and reduced remifentanil-mediated enhancement of spinal DRP1 and NR2B expression (P = 0.020 and P = 0.022). More importantly, AS-DRP1 reversed RIH-induced mitochondrial fission (P = 0.020) and mitochondrial superoxide upregulation (P = 0.031). Conclusions: These results indicate that AS-DRP1 could modulate NMDA receptor expression to prevent RIH through the DRP1-mitochondria-ROS pathway.

An electrocatalytic three-component reaction for the synthesis of phosphoroselenoates.

Phosphoroselenoates are important organic molecules because they have found widespread applications in many fields. Herein, an efficient electrochemical dehydrogenative approach to prepare phosphoroselenoates from (hetero)arenes and phosphonates using elemental selenium as the selenium source is reported. This approach is compatible with various functional groups and can be easily scaled up. Our control experiments revealed that electricity plays an important role in this transformation.

Electrochemical Oxidative C-C Bond Cleavage of Ketones for C-N Bond Formation: A Route to Amides.

Herein, we report an efficient electrochemical activation of the C-C bond of aryl ketones for the preparation of amides under catalyst- and external-oxidant-free conditions using aliphatic amines as the N source. Under environmentally benign electrolysis conditions, a series of amides were synthesized in good yield. Our control experiments revealed that electricity plays an important role in this transformation.

Analysis of risk factors for a poor functional prognosis and relapse in patients with autoimmune encephalitis.

This retrospective study analyzed the clinical characteristics of autoimmune encephalitis (AE) patients to explore the predictors of poor prognosis. According to the modified Rankin scale score at the last follow-up, the functional prognosis of the patients was reflected. And the prognosis of the patients was comprehensively evaluated by the functional prognosis and the relapse of the patients. The results showed that disturbance of consciousness and delayed first-line immunotherapy were independent risk factors for the poor functional prognosis of AE. In addition, patients with psychiatric symptoms, should be alert for relapse.

Understanding autism spectrum disorders with animal models: applications, insights, and perspectives.

Autism spectrum disorder (ASD) is typically characterized by common deficits in social skills and repetitive/stereotyped behaviors. It is widely accepted that genetic and environmental factors solely or in combination cause ASD. However, the underlying pathogenic mechanism is unclear due to its highly heterogeneous nature. To better understand the pathogenesis of ASD, various animal models have been generated, which can be generally divided into genetic, environment-induced, and idiopathic animal models. In this review, we summarize the common animals used for ASD study and then discuss the applications, clinical insights, as well as challenges and prospects of current ASD animal models.

Correction: Liu et al. Epichloë gansuensis Increases the Tolerance of Achnatheruminebrians to Low-P Stress by Modulating Amino Acids Metabolism and Phosphorus Utilization Efficiency. J. Fungi 2021, 7, 390.

Error in Figure [...].

Epichloë gansuensis Increases the Tolerance of Achnatherum inebrians to Low-P Stress by Modulating Amino Acids Metabolism and Phosphorus Utilization Efficiency.

In the long-term evolutionary process, Achnatherum inebrians and seed-borne endophytic fungi, Epichloë gansuensis, formed a mutually beneficial symbiosis relationship, and Epichloë gansuensis has an important biological role in improving the tolerance of host grasses to abiotic stress. In this work, we first assessed the effects of Epichloë gansuensis on dry weight, the content of C, N, P and metal ions, and metabolic pathway of amino acids, and phosphorus utilization efficiency (PUE) of Achnatherum inebrians at low P stress. Our results showed that the dry weights, the content of alanine, arginine, aspartic acid, glycine, glutamine, glutamic acid, L-asparagine, lysine, phenylalanine, proline, serine, threonine, and tryptophan were higher in leaves of Epichloë gansuensis-infected (E+) Achnatherum inebrians than Epichloë gansuensis-uninfected (E-) Achnatherum inebrians at low P stress. Further, Epichloë gansuensis increased C content of roots compared to the root of E- plant at 0.01 mM P and 0.5 mM P; Epichloëgansuensis increased K content of leaves compared to the leaf of E- plant at 0.01 mM P and 0.5 mM P. Epichloëgansuensis reduced Ca content of roots compared to the root of E- plant at 0.01 mM P and 0.5 mM P; Epichloë gansuensis reduced the content of Mg and Fe in leaves compared to the leaf of E- plant at 0.01 mM P and 0.5 mM P. In addition, at low P stress, Epichloë gansuensis most probably influenced aspartate and glutamate metabolism; valine, leucine, and isoleucine biosynthesis in leaves; and arginine and proline metabolism; alanine, aspartate, and glutamate metabolism in roots. Epichloë gansuensis also affected the content of organic acid and stress-related metabolites at low P stress. In conclusion, Epichloë gansuensis improves Achnatherum inebrians growth at low P stress by regulating the metabolic pathway of amino acids, amino acids content, organic acid content, and increasing PUE.

Wnt3a Inhibitor Attenuates Remifentanil-Induced Hyperalgesia via Downregulating Spinal NMDA Receptor in Rats.

PURPOSE: The upregulation of spinal NMDA receptor is a crucial mechanism in remifentanil-induced hyperalgesia (RIH). Wnt3a/ß-catenin pathway plays an important role in neuropathic pain. We hypothesized that wnt3a inhibitor (iwp-2) could downregulate the expression of NR2B subunit in NMDA receptor, in order to relieve RIH. MATERIALS AND METHODS: The study has 2 phases. The phase 1 study is designed by different doses of iwp-2 groups to create an appropriate iwp-2 dose used in RIH alleviation. The phase 2 study is designed to prove that the wnt3a inhibitor could downregulate the activation of the NR2B to inhibit RIH in rats. Thermal hyperalgesia (PWTL) and mechanical allodynia (PWMT) were evaluated after RIH. The area under the PWTL and PWMT curves (AUC) were calculated. The amount of activated NR2B subunit, c-fos, NF-κB, ß-catenin, wnt3a and p-GSK-3ß (Ser9) were detected in the lumbar spinal cord. RESULTS: Remifentanil infusion could induce overexpression of ß-catenin and wnt3a in rats. Iwp-2 (60µM, 120µM, 180µM) could dose-dependently inhibit thermal hyperalgesia and mechanical allodynia in rats. In phase 2 study, both NR2B subunit antagonist Ro25-6981 and iwp-2 decreased the amount of activated NR2B, enhanced p-GSK-3ß (Ser9), reduced ß-catenin, c-fos and NF-κB in the lumbar spinal cord (p < 0.001). In comparison with the group iwp-2, the group of Ro25-6981 had more benefit in reversing hyperalgesia, including higher AUC value of PWTL (p = 0.022) and PWMT (p = 0.035). CONCLUSION: Remifentanil exposure could induce overexpression of wnt3a and enhance the production of ß-catenin in the spinal dorsal horn. Inhibition of wnt3a response was capable of attenuating RIH in alleviating hyperalgesia-related behavioral parameters, as well as reducing overexpression of c-fos, NF-κB, NR2B in spinal dorsal horn.

CO2/Photoredox-Cocatalyzed Tandem Oxidative Cyclization of α-Bromo Ketones and Amines To Construct Substituted Oxazoles.

CO2/photoredox-cocatalyzed tandem oxidative cyclization of α-bromo ketones and amines for the preparation of substituted oxazoles has been achieved. The avoidance of using both transition-metal catalysts and peroxides makes this method more sustainable and renewable.

Combined treatment with vitamin K2 and PTH enhanced bone formation in ovariectomized rats and increased differentiation of osteoblast in vitro.

Osteoporosis is accompanied by insufficient osteogenic capacity. Several lines of evidence suggested that solutions to enhance osteoblastogenesis were important strategies for osteoporotic bone defect repair. This study investigated the effect of combined treatment with vitamin K2 and PTH on bone formation in calvarial bone defect in osteoporotic rats and its influence on osteoblast in vitro. Bilateral ovariectomy was used in SPF Sprague Dawley rats to generate an osteoporosis model. Subsequently, a calvarial defect model was established and all osteoporotic rats were randomly assigned to the following groups: control, VK (vitamin K2, 30 mg/kg everyday), PTH (recombinant human PTH (1-34), 60 µg/kg, three times a week) or VK + PTH (vitamin K2, 30 mg/kg everyday plus PTH, 60 µg/kg three times a week) for 8 weeks. In vitro, bone marrow-derived stem cells (BMSCs) were cultured and treated with vitamin K2, PTH or vitamin K2+PTH. ALP staining and western blot were performed to observe the influence of combined treatment on BMSCs. Bone formation within calvarial defect were assessed by serum γ-carboxylated osteocalcin (Gla-OC), micro-CT, histological and immunofluorescent labeling. In this study, combined treatment of PTH and vitamin K2 showed positive effects on preventing bone loss in femurs in OVX rats. Combined treatment increased serum Gla-OC and promoted bone formation in osteoporotic calvarial bone defects. Immunohistochemistry showed that OCN and RUNX2 were more highly expressed in the VK + PTH group than in the control groups. In vitro studies results suggested that combined treatment with PTH and vitamin K2 increased expression of ALP, BMP2 and RUNX2 in BMSCs. Our data suggested that the combination of vitamin K2 and PTH increased differentiation of osteoblast and had a synergistic effect on bone formation in osteoporotic calvarial bone defect.

Catalytic, metal-free alkylheteroarylation of alkenes via distal heteroaryl ipso-migration.

A new direct alkylheteroarylation of alkenes with simple alkylnitriles via distal heteroaryl ipso-migration has been accomplished under metal-free conditions, in which inexpensive alkylnitriles served as radical precursors, which together with ease of operation makes this process a very practical protocol.

Prognostic significance of NF-κB expression in non-small cell lung cancer: A meta-analysis.

Nuclear factor kappa B (NF-κB), a key nuclear transcription factor, is associated with prognosis in a variety of human cancers. However, the clinical value of NF-κB in non-small cell lung cancer (NSCLC) is still controversial. Therefore, the aim of this meta-analysis was to obtain an accurate evaluation of the relationship between NF-κB expression and survival prognosis of NSCLC patients based on published articles. PubMed, EMBASE and Web of Science databases were systematically searched for potential articles. A total of 1159 patients from 7 eligible studies comparing prognostic significance of NF-κB expression levels in NSCLC were included in our meta-analysis. I2 statistic and P value were performed to evaluate heterogeneity. The results of analysis were presented as hazard ratio (HR) or odds ratios (OR) with 95% confidence interval (95% CI). Subgroup analysis based on ethnicity of NSCLC patients and NF-kB cellular localization within cancer cells were conducted to illustrate the potential discrepancy. Significant heterogeneity was considered at I2>50% and P<0.05, and random-effects model was used. The combined results indicated that higher NF-κB expression was associated with shorter overall survival (OS) of NSCLC patients (HR = 2.78, 95% CI = 1.51-5.12, P = 0.001). Moreover, NF-κB expression was closely associated with tumor stage (HR = 0.32, 95% CI = 0.18-0.57, P<0.0001), lymph node metastasis (HR = 0.56, 95% CI = 0.38-0.83, P = 0.004) and 5-year OS for NSCLC patients (OR = 1.83, 95% CI = 1.02-3.31, P = 0.04). We conclude that NF-κB expression may be a potential unfavorable prognostic marker for NSCLC patients.

Factors Associated With Prolonged Viral Shedding in Patients With Avian Influenza A(H7N9) Virus Infection.

Background: Data are limited on the impact of neuraminidase inhibitor (NAI) treatment on avian influenza A(H7N9) virus RNA shedding. Methods: In this multicenter, retrospective study, data were collected from adults hospitalized with A(H7N9) infection during 2013-2017 in China. We compared clinical features and A(H7N9) shedding among patients with different NAI doses and combination therapies and evaluated factors associated with A(H7N9) shedding, using Cox proportional hazards regression. Results: Among 478 patients, the median age was 56 years, 71% were male, and 37% died. The median time from illness onset to NAI treatment initiation was 8 days (interquartile range [IQR], 6-10 days), and the median duration of A(H7N9) RNA detection from onset was 15.5 days (IQR, 12-20 days). A(H7N9) RNA shedding was shorter in survivors than in patients who died (P < .001). Corticosteroid administration (hazard ratio [HR], 0.62 [95% confidence interval {CI}, .50-.77]) and delayed NAI treatment (HR, 0.90 [95% CI, .91-.96]) were independent risk factors for prolonged A(H7N9) shedding. There was no significant difference in A(H7N9) shedding duration between NAI combination treatment and monotherapy (P = .65) or between standard-dose and double-dose oseltamivir treatment (P = .70). Conclusions: Corticosteroid therapy and delayed NAI treatment were associated with prolonged A(H7N9) RNA shedding. NAI combination therapy and double-dose oseltamivir treatment were not associated with a reduced A(H7N9) shedding duration as compared to standard-dose oseltamivir.

Direct alkylheteroarylation of alkenes via photoredox mediated C-H functionalization.

The direct alkylheteroarylation of alkenes with cyclic and acyclic ethers via distal heteroaryl ipso-migration has been accomplished through the design of a photoredox-mediated C-H functionalization pathway. The use of inexpensive ethers as radical precursors combined with a straightforward method makes this a practical approach.

High-intensity focused ultrasound (HIFU) treatment for uterine fibroids: a meta-analysis.

PURPOSE: High-intensity focused ultrasound (HIFU) is a non-invasive uterine-preserving treatment alternative to hysterectomy for women with fibroids. METHODS: We performed this meta-analysis to evaluate the efficacy of HIFU in the treatment of women with symptomatic fibroids comparing it to other approaches including medical treatment with mifepristone (Mife), traditional surgery with myomectomy or hysterectomy (MYC/HRM), and radiofrequency ablation (RF). 16 studies with 1725 women were included. RESULTS: The pooled data of HIFU comparing it to other methods in terms of complete or partial response rate (CR/PR) was not significantly better, but in subgroup analysis, the response rate was significantly higher than Mife, significantly lower than RF and comparable to MYC/HRM, respectively. For the endpoints of safety, the superiority of HIFU compared to MYC/HMR or Mife was found to be significant in terms of pain/discomfort, fever, transfusion, genital tract, gastrointestinal tract, and anesthesia-related complications, while no superiority was identified for skin burn, urinary tract, and nervous system complications. CONCLUSION: These results suggest that HIFU treatment of uterine leiomyomas leads to clinical improvement with few significant clinical complications and adverse events.

Transition-metal-free, visible-light induced cyclization of arylsulfonyl chlorides with o-azidoarylalkynes: a regiospecific route to unsymmetrical 2,3-disubstituted indoles.

A visible-light-catalyzed synthesis of unsymmetrical 2,3-diaryl-substituted indoles from arylsulfonyl chlorides and o-azidoarylalkynes at room temperature has been discovered. This transformation exhibits excellent substrate scope and functional group tolerance. The use of inexpensive eosin Y as the catalyst with easy operation makes this protocol very practical.

[Stiletto needle and needle-knife for influence of gravity index in treating knee osteoarthritis].

OBJECTIVE: To explore stiletto needle and needle-knife for influence of double sufficient weight in treating knee osteoarthritis patients. METHODS: One hundred and thirteen early and medium term knee osteoarthritis patients were randomly divided into three groups, including stiletto needle group(38 cases), needle-knife group (38 cases) and voltaren group (37 cases). In stiletto needle group, there were 13 males and 25 females with an average of(55.87±7.72) years old, treated by stiletto needle once a week, and 2 weeks were a course; there were 11 males and 27 females in needle-knife group with an average of(57.11±7.07) years old, treated by acupotome once a week, and 2 weeks were a course; there were 12 males and 25 females in voltaren group with an average age of(57.62±8.08) years old, treated by votalin emulsion smearing 3 to 5 cm on painful area of knee joint, three times a day for 2 weeks; 36 patients in normal group, including 11 males and 25 females with a mean age of (55.28±7.55) years old, treated with nothing. Gravitational four lattice used to measure bipedal back and forth load before and after treatment in further observe weight-bearing situation among three groups, d value, which was the distance from center of gravity to original point, was measured as a obvervational index, JOA score was used to evaluate clinical effect. RESULTS: Five patients were fall out, including 2 patients in stiletto needle group, 2 patients in needle-knife group and 1 patient in voltaren group. Other 108 patients were followed-up from 28 to 35 d with an average of 30 d, and without untoward effect. There was significant difference in d value between treatment group and control group at 1 month after treatment(P<0.05); there was significant difference in d value among treatment group at 1 month after treatment(P>0.05), and d value was decreased before treatment than that of after treatment. There was no significant difference in JOA score among treatment group after treatment at 1 month(P<0.05); while had significant difference between groups(P>0.05) after treatment at 1 month. CONCLUSIONS: Stiletto needle, needle-knife and voltaren for the treatment of knee osteoarthritis at early and middle stage, center of gravity is closer to original point, and weight-bearing is improved. It is a easy method of four lattice to measure change of weight-bearing in KOA patients after treatment.