Search

We have previously reported that Gypenoside LXXV (GP-75), a novel natural PPARγ agonist isolated from Gynostemma pentaphyllum, ameliorated cognitive deficits in db/db mice. In this study, we further investigated the beneficial effects on cognitive impairment in APP/PS1 mice and a mouse model of diabetic AD (APP/PS1xdb/db mice). Interestingly, intragastric administration of GP-75 (40 mg/kg/day) for 3 months significantly attenuated cognitive deficits in APP/PS1 and APP/PS1xdb/db mice. GP-75 treatment markedly reduced the levels of glucose, HbA1c and insulin in serum and improved glucose tolerance and insulin sensitivity in APP/PS1xdb/db mice. Notably, GP-75 treatment decreased the β-amyloid (Aβ) burden, as measured by

The immune profile in primary resected hypopharyngeal squamous cell carcinoma (HPSCC) and its prognostic value remain to be defined.We enrolled 100 patients with HPSCC underwent primary surgical resection at our department. HPSCC samples were examined using immunohistochemistry for the expressions of CD8, Foxp3, CD163, CD66B, programmed death ligand-1 (PD-L1), and interferon (IFN)-γ. The immune pattern of the tumor microenvironment (TME) was discriminated into inflamed and non-inflamed tumors based on the presence or absence of parenchymal CD8We found that 74% of HPSCC cases in our cohort were characterized by an immune-inflamed TME. Immune-inflamed patterns demonstrated an inferior survival with a significantly increased density of CD163The immune-inflamed pattern is the predominant preexisting immune phenotype in HPSCC and demonstrates immunosuppressive immune cell recruitment.

To review and analyse the evidence on the efficacy and safety of non-pharmacological interventions for preterm infants to relieve endotracheal suctioning (ES) pain.A systematic review per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.Six databases were searched with a retrieval strategy. Parallel and crossover randomized controlled trials reporting non-pharmacological interventions for relieving ES pain in preterm infants were identified from inception to 1 September 2021. The protocol was published in PROSPERO (CRD42021276058).Ten studies were retrieved, including nine different non-pharmacological interventions. Seven studies reported that non-pharmacological interventions in relieving pain were more effective than conventional care during ES, and three trials reported its safety. Due to the heterogeneity of pain assessment tools, time of assessment and population, only Facilitated tucking had sufficient evidence that it is a safe and effective non-pharmacological intervention.

Targeting the PPARγ might be a potential therapeutic strategy for diabetes-associated cognitive decline (DACD). In this study, Gypenoside LXXV (GP-75), a dammarane-type triterpene compound isolated from Gynostemma pentaphyllum, was found to be a novel PPARγ agonist using a dual-luciferase reporter assay system. However, whether GP-75 has protective effects against DACD remains unknown. Interestingly, intragastric administration of GP-75 (40 mg/kg/day) for 12 weeks significantly attenuated the cognitive deficit in db/db mice. GP-75 treatment significantly improved the glucose tolerance and lipid metabolism, and suppressed neuroinflammation. Notably, GP-75 treatment dramatically increased the uptake of glucose by the brain, as detected by

Spiro[azetidine-indolines] are important scaffolds in diverse bioactive compounds. Current efforts to synthesize spiro[azetidine-indolines] are limited to chiral spiro[azetidine-2,3'-indolines]. Asymmetric synthesis of structurally similar chiral spiro[azetidine-3,3'-indolines] remains unexplored. In this work, the first copper(I)-catalyzed asymmetric Kinugasa/aryl C-C coupling cascade reaction is described. This provides a straightforward access to densely functionalized chiral spiro[azetidine-3,3'-indoline]-2,2'-diones in good yields and with high enantioselectivity.

The advantages of urgent-start peritoneal dialysis (PD) vis-a-vis urgent-start hemodialysis (HD) are not clear. We performed a systematic review and meta-analysis of studies comparing the two modalities. Databases of PubMed, Embase, Ovoid, and Google Scholar were searched up to November 1, 2020. The primary outcome was mortality, and secondary outcomes were dialysis-related infectious complications and mechanical complications. Risk ratios (RRs) were calculated for all outcomes. Seven studies were included. The pooled analysis revealed a statistically significant reduced risk of all-cause mortality in patients undergoing urgent-start PD as compared to urgent-start HD (RR: 0.61, 95% confidence interval [CI] [0.40, 0.94], I2 = 56.34%). A meta-analysis of dialysis-related infectious complications indicated no statistically significant difference between the two modalities (RR: 0.66, 95% CI [0.29, 1.50], I2 = 69.62%). Our analysis revealed a statistically significant reduced risk of mechanical complications in patients undergoing urgent-start PD (RR: 0.54, 95% CI [0.40, 0.73], I2 = 0%). To conclude, unadjusted data from observational studies are indicative of lower mortality and lower risk of mechanical complications with urgent-start PD versus urgent-start HD. The risk of infectious complications was not different between the two groups. Further studies with a larger sample size using propensity-matched cohorts are needed to strengthen current evidence.

Background The histological grade of bladder cancer (BCa) is an important factor associated with the treatment and prognosis. However, accurate determination of the preoperative histological grade of BCa remains a challenge. Purpose To investigate the diagnostic potential of synthetic MRI (SyMRI) in evaluating the histological grade of BCa. Study type Prospective. Subjects Sixty patients (48 men and 12 women; mean age, 65 ± 11 years) with pathologically confirmed BCa (33 with high-grade BCa and 27 with low-grade BCa) were enrolled. Field strength/sequence Diffusion-weighted imaging (DWI) acquired by a single-shot echo-planar sequence and SyMRI acquired by a multidynamic multiecho (MDME) sequence at 3.0 T. Assessment Preoperative quantitative longitudinal relaxation time (T1 ), transverse relaxation time (T2 ), proton density (PD), and apparent diffusion coefficient (ADC) values of BCa were independently measured by two radiologists. Statistical tests Interclass correlation coefficient (ICC), independent sample t-test, Mann-Whitney U test, Delong test, and receiver operating characteristic curve (ROC) analysis were used. Results Significant differences were found in the mean of all the T1 , T2 , PD, and ADC values between high- and low-grade BCa. The best diagnostic performance was found for the mean ADC value with an area under the ROC curve (AUC) of 0.869, while the AUC values of the mean PD, T1 , and T2 values were 0.755, 0.740, and 0.723, respectively. Data conclusion SyMRI may be a potential noninvasive technique for evaluating the histological grade of BCa. However, the overall diagnostic performance of SyMRI-derived parameters was inferior to the ADC value. Levels of evidence 2. Technical efficacy stage 2.

Obstructive sleep apnea (OSA) has a high incidence and is harmful to health. It is characterized by repeated collapse of the upper airway. However, the mechanism underlying upper airway collapse is unclear.Patients with OSA and chronic tonsillitis were studied. Pathological changes in palatopharyngeus muscle were detected. The expression of peroxisome proliferator-activated receptor-γ co-activator-1α (PGC-1α) and nuclear respiratory factor-1 (NRF-1) in muscles was detected by PCR and Western blotting. Immunofluorescence staining was used to detect the expression of type I and type II myofibril.The structure of the palatopharyngeus muscle was changed, and the expression of PGC-1α and NRF-1 was decreased in the OSA group compared with that in the control group. The expression of PGC-1α, NRF-1, and type I myofibril in C2C12 myoblasts was decreased by intermittent hypoxia exposure. The expression of type I myofibril was decreased when knocking down PGC-1α.OSA patients exhibited pathological damage in palatopharyngeus muscle. PGC-1α was involved in the fiber type conversion in palatopharyngeus muscle caused by intermittent hypoxia.

Direct moxibustion (DM) is reported to be useful for cervical spondylotic radiculopathy (CSR), but the analgesic mechanism remains unknown. Autophagy plays a protective role in neuronal apoptosis, Act A/Smads signaling pathway has been confirmed to be associated with the activation of autophagy. The study aimed to explore the effect of DM on autophagy in rats with CSR and the involvement of Act A/Smads signaling pathway.Rats were randomly divided into Sham, CSR, CSR + DM, CSR + DM + 3-MA (PI3K inhibitor), and CSR + DM + SB (Act A inhibitor) group. Three days after establishment of CSR model with a fish line inserted under the axilla of the nerve roots, DM at Dazhui (GV14) was performed six times once for seven consecutive days. Western blot and immunofluorescence staining were used to observe the expression of the neuronal autophagy molecule LC3II/I, Atg7, and Act A/Smads signaling molecule Act A, p-Smad2, and p-Smad3. Bcl-2/Bax mRNA expression was measured by real time PCR.DM improved the pain threshold and motor function of CSR rats and promoted the expression of Act A, p-Smad2, p-Smad3, LC3II/I, and Atg7 in the entrapped-nerve root spinal dorsal horn. DM reduced the expression of Bax mRNA and decreased the number of apoptotic neurons. 3-MA and Act A inhibitor SB suppressed the expression of above-mentioned proteins and reduced the protective effect of DM on apoptotic neurons.DM exerts analgesic effects by regulating the autophagy to reduce cell apoptosis and repair nerve injury, and this feature may be related to the Act A/Smads signaling pathway.

The platysma skin flap was used for laryngeal reconstruction after vertical partial laryngectomy to improve the postoperative voice quality of patients with T2 and T3 glottic laryngeal carcinoma. Sixty-nine patients with unilateral T2 and T3 glottic laryngeal carcinoma were included. Forty-six patients received vertical partial laryngectomy, and a platysma skin flap was used for laryngeal reconstruction. The other 23 patients underwent transoral laser microsurgery. Subjective and objective examinations were performed to evaluate laryngeal morphology after the surgery. Acceptable voice quality was achieved for 46 patients who underwent vertical partial laryngectomy. Flap vibrational waves occurred in 19 cases (41.3%). The platysma skin flap is an ideal tissue for the reconstruction of articulation structure in open surgery of T2 and T3 unilateral glottic laryngeal carcinoma.

Tumor complexity makes the development of highly sensitive tumor imaging probes an arduous task. Here, we construct a peptide-based near-infrared probe that is responsive to fibroblast activation protein-α (FAP-α), and specifically forms nanofibers on the surface of cancer-associated fibroblasts (CAFs) in situ. The assembly/aggregation-induced retention (AIR) effect results in enhanced accumulation and retention of the probe around the tumor, resulting in a 5.5-fold signal enhancement in the tumor 48 h after administration compared to that of a control molecule that does not aggregate. The probe provides a prolonged detectable window of 48 h for tumor diagnosis. The selective assembly of the probe results in a signal intensity over four- and fivefold higher in tumor than in the liver and kidney, respectively. With enhanced tumor imaging capability, this probe can visualize small tumors around 2 mm in diameter.

Background To investigate whether the relative computed tomography (CT) value (rCT) of adjacent pancreatic parenchyma can distinguish focal‐type autoimmune pancreatitis (fAIP) from pancreatic ductal adenocarcinoma (PDAC). Methods A total of 13 patients with fAIP and 20 patients with PDAC were included in this study. The rCT was calculated as the ratio of the CT value of adjacent pancreatic parenchyma to that of muscle. The diagnostic performance of rCT for discriminating fAIP from PDAC was evaluated using receiver operating characteristic (ROC) analysis. Results Both fAIP and PDAC presented hyper‐fibrosis histologically and delayed enhancement on CT examination. Moreover, the pancreatic parenchyma of fAIP presented serious inflammation. The mean rCT of the parenchyma was significantly lower in fAIP than in PDAC in all phases. The best diagnostic performance of the rCT value was found in the pancreatic phase, with an area under the ROC curve of 0.912, while the areas under the ROC curve of the portal and delayed phases were 0.812 and 0.754, respectively. The optimal cut‐off value for distinguishing fAIP from PDAC was 1.62 in the pancreatic phase. Conclusions The rCT of the pancreatic parenchyma during the pancreatic phase may be a feasible CT feature for differentiating fAIP from PDAC., Similar imaging features such as regional enlargement of the pancreas and delayed enhancement became a big challenge to differentiate focal‐type autoimmune pancreatitis (fAIP) from PDAC. In this study, we found that the pancreatic parenchyma of fAIP presented severe inflammation. Moreover, the mean relative computed tomography values of the pancreatic parenchyma were lower in fAIP than that in PDAC in all phases.

Objective To investigate the effect of paraquat (PQ) exposure on gene expression in neural stem cells as well as structures and functions of vascular endothelial cells. Methods RNA-Seq was used to explore the differentially expressed genes in human umbilical cord blood-neural stem cells (HUCB-NSCs) at different stages (eg, proliferation, early and late differentiation) in the presence of PQ. The effects of PQ on human umbilical vein endothelial cells (HUVECs), including cell proliferation, apoptosis, cytokines secretion, and expression of tight junction proteins, were assessed with CCK-8, flow cytometry, ELISA, and western blot analysis, individually. Results A total of 53 genes were up-regulated and 61 genes were down-regulated in PQ treated HUCB-NSCs, including seven genes associated with the differentiation of neural stem cells, for example, Gfap, S100B, Oct4, Gdf3, Sox1, Pax6, and Ngn1. PQ treatment significantly reduced the proliferation of HUVECs, inhibited cytokines secretion (VEGF, BFGF) and expressions of tight junction-associated protein (Claudin 1, Occludin, ZO-1), as well as induced significant apoptosis. Conclusion Our study suggests that PQ impairs the development of nervous system by regulating the expression of genes associated with neural stem cell differentiation, as well as the structure and function of vascular endothelial cells, which together lead to abnormality in the nervous system.

Background Thyroglossal duct cysts (TDCs) are usually resected through an incision over the entire protruding zone. The resulting scar is aesthetically displeasing, so we explored the use of endoscope-assisted excision of TDCs via a submaxillary vestibular approach. The purpose of this study was to demonstrate the feasibility, validity, and safety of this approach and to evaluate the follow-up results. Methods From January 2007 to August 2015, 16 patients with TDCs underwent surgical resection using a submaxillary vestibular approach. Results All procedures were successfully performed using endoscope-assisted surgery via a submaxillary vestibular approach. There were no postoperative complications and no conversions of the operation. The average follow-up period was 73 months (range 14-117 months) without recurrence. All patients and their families were satisfied with the cosmetic results. Conclusion Endoscope-assisted excision of TDCs using a submaxillary vestibular approach is feasible and can be applied effectively and safely with good cosmetic results. Therefore, this method should be considered a viable alternative approach for these patients.

An efficient and practical approach to 3a-azidofuroindolines and -pyrroloindolines involving an iodine-catalyzed azidation/cyclization cascade of tryptophols and tryptamines with NaN3 was developed. Further transformation of the C3-azidated product provided a key intermediate for the total synthesis of psychotriasine.

Angioimmunoblastic T-cell lymphomas (AITLs) frequently carry mutations in the TET2 and IDH2 genes. TET2 mutations represent early genetic lesions as they had already been detected in haematopoietic precursor cells of AITL patients. We show by analysis of whole-tissue sections and microdissected PD1+ cells that the frequency of TET2-mutated AITL is presumably even higher than reported (12/13 cases in our collection; 92%). In two-thirds of informative AITLs (6/9), a fraction of B cells was also TET2-mutated. Investigation of four AITLs by TET2 and IGHV gene sequencing of single microdissected B cells showed that between 10% and 60% of polyclonal B cells in AITL lymph nodes harboured the identical TET2 mutations of the respective T-cell lymphoma clone. Thus, TET2-mutated haematopoietic precursor cells in AITL patients not only give rise to the T-cell lymphoma but also generate a large population of mutated mature B cells. Future studies will show whether this is a reason why AITL patients frequently also develop B-cell lymphomas. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

POEMS syndrome is a rare plasma cell dyscrasia. Serum concentrations of the monoclonal protein in this disorder are typically low, and inapplicable to monitor disease activity in most cases, resulting in limited practical and prognostic values. Novel immunoassays measuring isotype-specific heavy/light chain (HLC) pairs showed its utility in disease monitoring and outcome prediction in several plasma cell dyscrasias. We report results of HLC measurements in 90 patients with POEMS syndrome. Sixty-six patients (73%; 95% confidence interval, 63-82%) had an abnormal HLC ratio at baseline. It could stratify the risk of disease relapse and was strongly associated with worse progression-free survival in a multivariate analysis (P = 0.021; hazard ratio [HR] 6.89, 95% CI 1.34-35.43). After therapy, HLC ratios improved, with 43 patients (48%) remaining abnormal. The post-therapeutic HLC ratio, if abnormal, also remained as an independent prognostic factor associated with worse progression-free survival (P = 0.019; HR 4.30, 95% CI 1.27-14.56). These results suggest the prognostic utility of HLC ratios in clinical management of POEMS patients.

Nanomaterial-based generators are a highly promising power supply for micro/nanoscale devices, capable of directly harvesting energy from ambient sources without the need for batteries. These generators have been designed within four main types: piezoelectric, triboelectric, thermoelectric, and electret effects, and consist of ZnO-based, silicon-based, ferroelectric-material-based, polymer-based, and graphene-based examples. The representative achievements, current challenges, and future prospects of these nanogenerators are discussed.

Spirobicyclic structures are versatile building blocks for functional chiral molecules. An enantioselective synthesis of chiral spirobilactams via a copper-catalyzed double N-arylation was developed. Amplification of solution ee by in situ precipitation of the racemate was observed with this method and enantioenriched spirobilactams were obtained with excellent ee values through simple solid-solution phase separation.

O-Heterocyclic structures such as 2,3-dihydrobenzofurans are key motifs in many natural compounds and pharmaceuticals. Enantioselective formation of chiral dihydrobenzofurans and analogues was achieved through a copper-catalyzed desymmetrization strategy with a chiral cyclic 1,2-diamine. A broad range of substrates are compatible with this Cu(I)-diamine catalytic system and afford the desired coupling products with chiral tertiary or quaternary carbon centers in high yields and good to excellent enantioselectivities under mild conditions.

Epithelial-mesenchymal transition (EMT) is believed to be involved in lung fibrosis process induced by paraquat (PQ); however, the molecular mechanism of this process has not been clearly established. The present study investigated the potential involvement of EMT after PQ poisoning. The expressions of EMT markers, such as E-cadherin and α-smooth muscle actin (α-SMA), at multiple time points after exposure to different concentrations of PQ were evaluated by western blot analysis. Following PQ treatment, EMT induction was observed under microscopy. Related fibrosis genes, including Matrix metalloproteinase 2 (MMP-2), Matrix metalloproteinase 9 (MMP-9), collagens type I (COL I), and type III (COL III), were also evaluated by measuring their mRNA levels using RT-PCR analysis. Signaling pathways were analyzed using selective pharmacological inhibitors for MAPK. Cell migration ability was evaluated by scratch wound and Transwell assays. The data showed that PQ-induced epithelial RLE-6NT cells to develop mesenchymal cell characteristics, as indicated by a significant decrease in the epithelial marker E-cadherin and a significant increase in the extracellular matrix (ECM) marker α-smooth muscle actin in a dose and time-dependent manner. Moreover, PQ-treated RLE-6NT cells had an EMT-like phenotype with elevated expression of MMP-2, MMP-9, and COL I and COL III and enhanced migration ability. Signal pathway analysis revealed that PQ-induced EMT led to ERK-1 and Smad2 phosphorylation through activation of the MAPK pathway. The results of the current study indicate that PQ-induced pulmonary fibrosis occurs via EMT, which is mediated by the MAPK pathway. This implies that the MAPK pathway is a promising therapeutic target in alveolar epithelial cells. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1407-1414, 2016.

During a screening program for new agrochemicals from Chinese medicinal herbs and local wild plants, the petroleum ether (PE) extract of Atractylodes lancea (Thunb.) rhizomes was found to possess repellent and contact activities against Tribolium castaneum adults. Bioactivity-directed chromatographic separation of PE extract on repeated silica-gel columns led to the isolation of two polyacetylenes, atractylodin and atractylodinol (1 and 2, resp.), and two lactones, atractylenolides II and III (3 and 4, resp.). The structures of the compounds were elucidated based on NMR spectra. The four isolated compounds were evaluated for their insecticidal and repellent activities against T. castaneum. Atractylodin exhibited strong contact activity against T. castaneum adults with a LD50 value of 1.83 μg/adult. Atractylodin and atractylenolide II also possessed strong repellenct activities against T. castaneum adults. After 4-h exposure,90% repellency was achieved with atractylodin at a low concentration of 0.63 μg/cm(2) . The results indicated that atractylodin (1) and atractylenolide II (3) have a good potential as a source for natural repellents, and 1 has the potential to be developed as natural insecticide.

An asymmetric synthesis of N-aryl sulfinamides was achieved through copper-catalyzed coupling reactions of aryl iodides with sulfinamides. Such a kinetic resolution process provided the desired coupling products in moderate to good yields and with moderate enantioselectivities.

Transition metal catalyzed coupling reactions of aryl halides with nucleophiles are valuable methods for the formation of aryl carbon–carbon or aryl carbon–heteroatom bonds. However, little attention has been focused on the asymmetric versions of such couplings. Besides direct coupling for the formation of axial chirality, asymmetric desymmetrization and kinetic resolution are two important strategies for achieving enantioselectivity in transition metal catalyzed aryl carbon–heteroatom couplings. This account summarizes recent progress made in our group on copper- or palladium-catalyzed asymmetric aryl carbon–nitrogen/oxygen coupling reactions using asymmetric desymmetrization or kinetic resolution strategies. 1 Introduction 2 Copper-Catalyzed Asymmetric N-Arylation 2.1 N-Arylation via Asymmetric Desymmetrization 2.1.1 First Type of Desymmetric N-Arylation 2.1.2 Second Type of Desymmetric N-Arylation 2.1.3 Double N-Arylation for Spirobilactams 2.2 N-Arylation via Kinetic Resolution 3 Asymmetric O-Arylation 3.1 Palladium/Spirocyclic Diphosphine Ligand System for O-Aryl­ation via Asymmetric Desymmetrization 3.2 Palladium/Spirocyclic Diphosphine Monoxide Ligand System for O-Arylation via Asymmetric Desymmetrization 3.3 Copper/Diamine System for O-Arylation via Asymmetric Desymmetrization 4 Summary and Outlook

Copper-catalyzed (or -mediated) asymmetric coupling reactions have received significant attention over the past few years. Especially the coupling reactions of aryl or alkyl halides with nucleophiles became a very powerful tool for the formation of C–C, C–N, C–O and other carbon–heteroatom bonds as well as for the construction of heteroatom-containing ring systems. This review summarizes the recent progress in copper-catalyzed asymmetric coupling reactions for the formation of C–C and carbon–heteroatom bonds.

A copper-catalyzed enantioselective N-arylation for the formation of cyano-bearing all-carbon quaternary stereocenters was developed via kinetic resolution of racemic 3-amino-2-(2-iodobenzyl)propanenitriles. The reaction afforded the desired coupling products in moderate enantioselectivity under catalysis by CuI and a BINOL-derived ligand.

A series of title compounds is prepared as building blocks for functional chiral molecules.