Pyridine-borane complex-catalysed thioesterification: the direct conversion of carboxylic acids to thioesters.

Thioesters are a common class of biologically active fragments and synthetically useful building blocks. An attractive synthetic approach would be to use simple and bench-stable carboxylic acids as a coupling partner. Herein, we present a 4-bromo pyridine-borane complex as a catalyst for the direct coupling of carboxylic acids with thiols. A wide range of thioesters with good functional group compatibility could be prepared via this metal-free approach. The merit of this strategy is exemplified by the modification of carboxylic acid-containing drugs.

Inflammation and Connexin 43 profiles in the prefrontal cortex are relevant to stress susceptibility and resilience in mice.

Depression is a major chronic mental illness worldwide, characterized by anhedonia and pessimism. Exposed to the same stressful stimuli, some people behave normally, while others exhibit negative behaviors and psychology. The exact molecular mechanisms linking stress-induced depressive susceptibility and resilience remain unclear. Connexin 43 (Cx43) forms gap junction channels between the astrocytes, acting as a crucial role in the pathogenesis of depression. Cx43 dysfunction could lead to depressive behaviors, and depression down-regulates the expression of Cx43 in the prefrontal cortex (PFC). Besides, accumulating evidence indicates that inflammation is one of the most common pathological features of the central nervous system dysfunction. However, the roles of Cx43 and peripheral inflammation in stress-susceptible and stress-resilient individuals have rarely been investigated. Thus, animals were classified into the chronic unpredictable stress (CUS)-susceptible group and the CUS-resilient group based on the performance of behavioral tests following the CUS protocol in this study. The protein expression of Cx43 in the PFC, the Cx43 functional changes in the PFC, and the expression levels including interleukin (IL)-1ß, tumor necrosis factor-α, IL-6, IL-2, IL-10, and IL-18 in the peripheral serum were detected. Here, we found that stress exposure triggered a significant reduction in Cx43 protein expression in the CUS-susceptible mice but not in the CUS-resilient mice accompanied by various Cx43 phosphorylation expression and the changes of inflammatory signals. Stress resilience is associated with Cx43 in the PFC and fluctuation in inflammatory signaling, showing that therapeutic targeting of these pathways might promote stress resilience.

Reorganization of intrinsic functional connectivity in early-stage Parkinson's disease patients with probable REM sleep behavior disorder.

REM sleep behavior disorder (RBD) symptoms in Parkinson's disease (PD) suggest both a clinically and pathologically malignant subtype. However, whether RBD symptoms are associated with alterations in the organization of whole-brain intrinsic functional networks in PD, especially at early disease stages, remains unclear. Here we use resting-state functional MRI, coupled with graph-theoretical approaches and network-based statistics analyses, and validated with large-scale network analyses, to characterize functional brain networks and their relationship with clinical measures in early PD patients with probable RBD (PD+pRBD), early PD patients without probable RBD (PD-pRBD) and healthy controls. Thirty-six PD+pRBD, 57 PD-pRBD and 71 healthy controls were included in the final analyses. The PD+pRBD group demonstrated decreased global efficiency (t = -2.036, P = 0.0432) compared to PD-pRBD, and decreased network efficiency, as well as comprehensively disrupted nodal efficiency and whole-brain networks (all eight networks, but especially in the sensorimotor, default mode and visual networks) compared to healthy controls. The PD-pRBD group showed decreased nodal degree in right ventral frontal cortex and more affected edges in the frontoparietal and ventral attention networks compared to healthy controls. Furthermore, the assortativity coefficient was negatively correlated with Montreal cognitive assessment scores in the PD+pRBD group (r = -0.365, P = 0.026, d = 0.154). The observation of altered whole-brain functional networks and its correlation with cognitive function in PD+pRBD suggest reorganization of the intrinsic functional connectivity to maintain the brain function in the early stage of the disease. Future longitudinal studies following these alterations along disease progression are warranted.

Mitochondrial stress induces hepatic stellate cell activation in response to the ATF4/TRIB3 pathway stimulation.

BACKGROUND: The activation of hepatic stellate cells (HSCs) is the key step in the pathogenesis of liver fibrosis, which directly leads to fibrotic pathological changes in the hepatic tissue. Mitochondrial stress exacerbates inflammatory diseases by inducing pathogenic shifts in normal cells. However, the role of mitochondrial stress in HSC activation remains to be elucidated.  METHODS: We analyzed the effect of mitochondrial stress on HSC activation. An in vivo hepatic fibrosis model was established by intraperitoneal injection of 40% carbon tetrachloride (CCl4) for 12 weeks. Additionally, using in vitro approach, HSC-T6 cells were treated with 10 ng/mL platelet-derived growth factor-BB (PDGF-BB) for 24 h. RESULTS: Transcriptional activator 4 (ATF4) is highly expressed in fibrotic liver tissue samples and activated HSCs. We found that AAV8-shRNA-Atf4 alleviated liver fibrosis in rats. ATF4 promoted the activation of HSCs, which was induced by mitochondrial stress. The mechanisms involved ATF4 binding to a specific region of the tribble homologue 3 (TRIB3) promoter. Further, TRIB3 promoted HSCs activation mediated by mitochondrial stress. CONCLUSIONS: ATF4 induces mitochondrial stress by upregulating TRIB3, leading to the activation of HSCs. Therefore, the inhibition of ATF4 during mitochondrial stress may be a promising therapeutic target for liver fibrosis.

Identification of Human Body Fluid Stains and Non-Biological Stains by Three-Dimensional Fluorescence Spectroscopy.

OBJECTIVES: To establish a rapid and nondestructive identification method for human body fluid stains and non-biological stains using three-dimensional fluorescence spectroscopy. METHODS: The collected three-dimensional fluorescence spectrum data of human saliva, 3% blood, coffee and Fanta® stains were processed with dimensionality reduction. After wavelet transform, spectral denoising and feature extraction, the classification formula was established. The Fisher discriminant was used for spectrum matching and recognition to establish the analysis method to distinguish stain types. RESULTS: According to the results of data training and comparison, all the recognition accuracies of Fanta®, coffee, saliva and blood were more than 91.39%. Among them, saliva reached 100% recognition accuracy. CONCLUSIONS: Three-dimensional fluorescence spectroscopy is a potential method for rapid and nondestructive identification of biological and non-biological stains.

Application of transcriptome in time analysis and donor characterization in blood samples.

As an effective supplement to the current forensic DNA typing and one of the research hotpots in forensic science, the in-depth mining and characterization of biological evidence can provide rich and reliable clues for case investigation. In this study, the time-dependent variations of transcriptome were confirmed in in vitro blood samples within 0-168 days and a random forest model was established to realize the classification of blood samples with different TSD (time since deposition). Meanwhile, significant differences were observed in the transcripts of blood samples with different smoking habits and genders within a certain time period. HLA-DRB1, HLA-DQB1 and HLA-DQA2 were identified as markers for smoking habit identification, while the transcripts for RPS4Y1 and EIF1AY from the non-recombining region of the Y chromosome (NRY) were identified as markers for male sex identification. Thus, this study provides a theoretical foundation and experimental strategy for establishing a transcriptome-based method for characterizing blood sample retention time and donor characteristics in the field of forensic investigation.

[Quality standard and quality value transfer of reference samples of classical prescription Huagan Decoction].

The detection method of characteristic spectrum for reference samples was established by preparing 15 batches of the reference samples of Huagan Decoction, and the peak attribution and the similarity range in the characteristic spectrum were clarified. The ranges of paste-forming rate, content, and transfer rate of the index components including geniposide, paeonol, and paeoniflorin were analyzed. The key quality attribute of the reference samples of Huagan Decoction was defined. The results showed that the 15 batches of the reference samples of Huagan Decoction had good similarities in the characteristic spectrum, which were all higher than 0.9. According to the information of characteristic peak, there were 18 characteristic peaks in the whole prescription, including seven common characteristic peaks from green tangerine peel and dried tangerine peel, four characteristic peaks from tree peony root bark(three of them were common characteristic peaks from tree peony root bark and red peony root), five characteristic peaks from cape jasmine fruit, one characteristic peak from paniculate bolbostemma, and one characteristic peak from oriental waterplantain rhizome.The paste-forming rate of the 15 batches of reference samples was 14.73%-18.83%. The content of geniposide was 1.68%-2.87%, with the average transfer rate of 70.05%±11.13%. The content of paeonol was 0.10%-0.16%, with the average transfer rate of 9.38%±1.78%. The content of paeoniflorin was 1.94%-2.74%, with the average transfer rate of 36.69%±4.63%. This study analyzed the quality value transfer of the reference samples of Huagan Decoction by the evaluation mode of combining the characteristic spectrum, the paste-forming rate, and the content of index components. The findings of this study initially established a stable and feasible standard decoction evaluation method and provided references for the quality control and the subsequent development of relevant preparations of Huagan Decoction.

A Facile Microwave Hydrothermal Method for Fabricating SnO2@C/Graphene Composite With Enhanced Lithium Ion Storage Properties.

SnO2@C/graphene ternary composite material has been prepared via a double-layer modified strategy of carbon layer and graphene sheets. The size, dispersity, and coating layer of SnO2@C are uniform. The SnO2@C/graphene has a typical porous structure. The discharge and charge capacities of the initial cycle for SnO2@C/graphene are 2,210 mAh g-1 and 1,285 mAh g-1, respectively, at a current density of 1,000 mA g-1. The Coulombic efficiency is 58.60%. The reversible specific capacity of the SnO2@C/graphene anode is 955 mAh g-1 after 300 cycles. The average reversible specific capacity still maintains 572 mAh g-1 even at the high current density of 5 A g-1. In addition, cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) are performed to further investigate the prepared SnO2@C/graphene composite material by a microwave hydrothermal method. As a result, SnO2@C/graphene has demonstrated a better electrochemical performance.

Association between HLA alleles and sub-phenotype of childhood steroid-sensitive nephrotic syndrome.

BACKGROUND: Few studies have addressed the effects of human leukocyte antigen (HLA) alleles on different clinical sub-phenotypes in childhood steroid-sensitive nephrotic syndrome (SSNS), including SSNS without recurrence (SSNSWR) and steroid-dependent nephrotic syndrome/frequently relapse nephrotic syndrome (SDNS/FRNS). In this study, we investigated the relationship between HLA system and children with SSNSWR and SDNS/FRNS and clarified the value of HLA allele detection for precise typing of childhood SSNS. METHODS: A total of 241 Chinese Han individuals with SSNS were genotyped using GenCap-WES Capture Kit, and four-digit resolution HLA alleles were imputed from available Genome Wide Association data. The distribution and carrying frequency of HLA alleles in SSNSWR and SDNS/FRNS were investigated. Additionally, logistic regression and mediating effects were used to examine the relationship between risk factors for disease process and HLA system. RESULTS: Compared with SSNSWR, significantly decreased serum levels of complement 3 (C3) and complement 4 (C4) at onset were detected in SDNS/FRNS (C3, P < 0.001; C4, P = 0.018). The average time to remission after sufficient initial steroid treatment in SDNS/FRNS was significantly longer than that in SSNSWR (P = 0.0001). Low level of C4 was further identified as an independent risk factor for SDNS/FRNS (P = 0.008, odds ratio = 0.174, 95% confidence interval 0.048-0.630). The HLA-A*11:01 allele was independently associated with SSNSWR and SDNS/FRNS (P = 0.0012 and P = 0.0006, respectively). No significant HLA alleles were detected between SSNSWR and SDNS/FRNS. In addition, a mediating effect among HLA-I alleles (HLA-B*15:11, HLA-B*44:03 and HLA-C*07:06), C4 level and SDNS/FRNS was identified. CONCLUSIONS: HLA-I alleles provide novel genetic markers for SSNSWR and SDNS/FRNS. HLA-I antigens may be involved in steroid dependent or frequent relapse in children with SSNS as mediators of immunoregulation.

Localization of subcentimeter pulmonary nodules using an indocyanine green near-infrared imaging system during uniportal video-assisted thoracoscopic surgery.

BACKGROUND: To investigate the feasibility of indocyanine green (ICG) use in localizing subcentimeter pulmonary nodules during uniportal video-assisted thoracoscopic surgery. METHODS: This study was a retrospective analysis of 32 patients who underwent surgery due to pulmonary nodules using ICG localization from September 2019 to March 2020 in the Department of Thoracic Surgery, The Fourth Affiliated Hospital of China Medical University. Laser positioning and large-aperture spiral CT simulation were performed preoperatively. ICG was injected into the lung (2.5 mg/ml). The clinical characteristics and postoperative indicators were recorded. RESULTS: A total of 33 subcentimeter pulmonary nodules were successfully localized in 32 patients. Twenty-three patients underwent lobectomy, with an average surgical time of 45.3 min and an average tube retention time of 2 days. Non-small cell lung cancer was confirmed intraoperatively in 9 patients, among whom the longest surgical time was 120 min, and the shortest hospital stay was 7 days. No patient was converted to thoracotomy or developed serious complications. CONCLUSIONS: ICG imaging is a safe and effective technique for localization of pulmonary nodules. Due to the widespread application of near-infrared devices, fluorescent localization and imaging technology will be more widely used in thoracic surgery.

Bénard-von Kármán vortex street in a spin-orbit-coupled Bose-Einstein condensate.

The dynamics of pseudo-spin-1/2 Bose-Einstein condensates with weak spin-orbit coupling through a moving obstacle potential are studied numerically. Four types of wakes are observed and the phase diagrams are determined for different spin-orbit coupling strengths. The conditions to form Bénard-von Kármán vortex street are rather rigorous, and we investigate in detail the dynamical characteristics of the vortex streets. The two point vortices in a pair rotate around their center, and the angular velocity and their distance oscillate periodically. The oscillation intensifies with increasing spin-orbit coupling strengths, and it makes part of the vortex pairs dissociate into separate vortices or combine into single ones and destroys the vortex street in the end. The width b of the street and the distance l between two consecutive vortex pairs of the same circulation are determined by the potential radius and its moving velocity, respectively. The b/l ratios are independent of the spin-orbit coupling strength and fall in the range 0.19-0.27, which is a little smaller than the stability criterion 0.28 for classical fluids. Proper b/l ratios are necessary to form Bénard-von Kármán vortex street, but the spin-orbit coupling strength affects the stability of the street patterns. Finally, we propose a protocol to experimentally realize the vortex street in ^{87}Rb spin-orbit-coupling Bose-Einstein condensates.

Combined use of transversus abdominis plane block and laryngeal mask airway during implementing ERAS programs for patients with primary liver cancer: a randomized controlled trial.

The incidence and mortality of primary liver cancer are very high and resection of tumor is the most crucial treatment for it. We aimed to assess the efficacy and safety of combined use of transversus abdominis plane (TAP) block and laryngeal mask airway (LMA) during implementing Enhanced Recovery After Surgery (ERAS) programs for patients with primary liver cancer. This was a prospective, evaluator-blinded, randomized, controlled parallel-arm trial. A total of 96 patients were enrolled (48 in each group). Patients in the control group received general anesthesia with endotracheal intubation, while patients in the TAP + LMA group received general anesthesia with LMA and an ultrasound-guided subcostal TAP block. The primary end-point was postoperative time of readiness for discharge. The secondary end-points were postoperative pain intensity, time to first flatus, quality of recovery (QoR), complications and overall medical cost. Postoperative time of readiness for discharge in the TAP + LMA group [7 (5-11) days] was shorter than that of the control group [8 (5-13) days, P = 0.004]. The postoperative apioid requirement and time to first flatus was lower in the TAP + LMA group [(102.8 ± 12.4) µg, (32.7 ± 5.8) h, respectively] than the control group [(135.7 ± 20.1) µg, P = 0.000; (47.2 ± 7.6) h, P = 0.000; respectively]. The QoR scores were significantly higher in the TAP + LMA group than the control group. The total cost for treatment in the TAP + LMA group [(66,608.4 ± 6,268.4) CNY] was lower than that of the control group [(84,434.0 ± 9,436.2) CNY, P = 0.000]. There was no difference in complications between these two groups. The combined usage of a TAP block and LMA is a simple, safe anesthesia method during implementing ERAS programs for patients with primary liver cancer. It can alleviate surgical stress, accelerate recovery and reduce medical cost.

A 4-gene prognostic signature predicting survival in hepatocellular carcinoma.

OBJECTIVE: To develop an independent prognostic signature for patients with hepatocellular carcinoma (HCC). METHODS: HCC gene expression profile the cancer genome atlas-liver hepatocellular carcinoma and GSE14520 were used as discovery and test set, respectively. Differentially expressed genes (DEGs) were identified between HCC tissues and adjacent normal liver tissues. Univariate Cox proportional hazards regression analysis was performed to identify DEGs correlated with survival of HCC patients. A 4-gene-based signature was constructed based on a least absolute shrinkage and selection operator Cox penalized regression model. The predictive value of the signature was analyzed and validated. RESULTS: Two hundred sixty-three DEGs were identified between HCC and adjacent liver tissues. After univariate survival analysis, 90 DEGs were found to be significantly correlated with the overall survival (OS) of HCC patients, of which 4 genes (KPNA2, CDC20, SPP1, and TOP2A) with non-zero coefficient were used to construct a prognostic signature. The 4-gene signature was significantly associated with the age (P = 0.046), grade ( P = 0.022), and T stage ( P = 0.023) of HCC patients in the discovery set and it also significantly associated with TNM stage ( P = 0.033), and serum alpha-fetoprotein lever ( P = 0.034). Patients in the 4-gene low-risk group were associated with better OS and recurrence-free survival (RFS) than those in the high-risk group in the discovery and test set. Meanwhile, the 4-gene signature is an independent prognostic factor regarding OS and RFS in the discovery and test set. CONCLUSION: We developed a 4-gene-based signature, which could be a candidate prognostic factor for patients with HCC.

Elevation of the Chemokine Pair CXCL10/CXCR3 Initiates Sequential Glial Activation and Crosstalk During the Development of Bimodal Inflammatory Pain after Spinal Cord Ischemia Reperfusion.

BACKGROUND/AIMS: Spinal microglia and astrocytes are the main responders to the inflammatory cascade and process pain through various neural interactions. CXCL10 is a late-phase protein that accelerates arteriogenesis during reperfusion through CXCR3. However, the early-phase expression (within 72 h postoperatively) of CXCL10 and CXCR3 during the development of ischemia-reperfusion (IR)-induced inflammatory pain remains unclear. We investigated whether this chemokine pair participates in glial interactions during early-phase IR injury. METHODS: A rat model was induced by an 8-min occlusion of the aortic arch. Temporal assessments of mechanical and thermal allodynia and the protein levels of CXCL10 and CXCR3 were determined through measurements of paw withdrawal thresholds (PWTs) and paw withdrawal latencies (PWLs) and Western blotting assays. The co-localization of various cells with glial cells was detected by double immunofluorescence. The effects of CXCL10/CXCR3 on glial interactions were explored by intrathecal treatment with specific inhibitors (AMD487, minocycline and fluorocitrate) and recombinant CXCL10, and subsequent release of cytokines was assessed by ELISAs. RESULTS: The IR injury initiated bimodal allodynia within 72 h of reperfusion, as illustrated by two W-shape trends in the PWTs and PWLs with two minima at 12 and 48 h post-IR. Allodynia was highly correlated with overexpression of CXCL10 and CXCR3, which were expressed in microglia at the early stage and in both microglia and astrocytes at the late stage, as shown by increased CXCL10 and CXCR3 immunoreactivities and double-labeled cells. AMD487 and minocycline injections exerted comparable inhibitory effects on CXCR3 and Iba-1 and on GFAP immunoreactivity at 12 and 48 h post-IR, and these inhibitory effects were only observed at 48 h following fluorocitrate injection. The levels of TNF-α and IL-6 showed variations in concert with the changes in Iba-1 and GFAP immunoreactivities. Recombinant CXCL10 injection reversed the abovementioned effects. CONCLUSION: The results showed that CXCL10/CXCR3 are involved in bimodal inflammatory pain during early-phase IR injury. The sequential activation of and crosstalk between microglia and astrocytes mediated through CXCR3 upregulation suggested that treatments targeting specific cell types are important in post-IR allodynia.

Effects of the ultra-high pressure on structure and α-glucosidase inhibition of polysaccharide from Astragalus.

A novel homogeneous polysaccharide fraction (APS) was extracted from Astragalus by hot water and purified by Sephadex G-100 and G-75 column. Its molecular weight was 693kDa. APS and APS with ultra-high pressure treatment exhibited significant inhibitory abilities on a-glucosidase, inhibition rate from high to low in order was 400MPa-APS, 300MPa-APS, 500MPa-APS and APS. The inhibition ​percentage of 400MPa-APS (1.5mg/mL) was 49% (max.). This suggested that the inhibitory activity of APS on a-glucosidase was improved by ultra-high pressure treatment. FT-IR, SEM, CD spectra, atomic force microscope and Congo red test analysis of APS and 400MPa-APS showed ultra-high pressure treatment didn't change the preliminary structure but had an effect on its advanced structure.

Structural characterization and anti-tumor activity of polysaccharide produced by Hirsutella sinensis.

HSP-III, a novel homogeneous polysaccharide with 513.89 kDa molecular weight, was fractionated from submerged cultures of Hirsutella sinensis by Sevag and chromatography on Sephadex G-100 column. The total sugar content of HSP-III was amounted to 89.87%. Based on the results of high performance gel permeation chromatogram (HPGPC), FT-IR, NMR spectroscopy, GC, periodate oxidation-smith degradation and methylation analysis, it showed that HSP-III was mainly composed of mannose and galactose, and a small amount of rhamnose, arabinose, xylose, and glucose. The molar ratio of Rha:Ara:Xyl:Man:Glu:Gal was 1.00:2.44:13.11:74.13:13.80:54.39. The main chain of HSP-III was majorly composed of (1→3) glucose. The tumor inhibition ratio on H22 cell was 79.04% at 100 µg/mL of HSP-III.

The metabolism of trifluoperazine (TFP) exhibits atypical kinetic behavior in both human liver microsomes (HLMs) and monkey liver microsomes (MyLM).

Glucuronidation reaction of trifluoperazine (TFP) is a typical probe reaction to phenotype the activity of UDP-glucuronosyltransferase 1A4. The present study aims to compare the metabolic behavior of TFP in the liver microsomes from human and cynomolgus monkey, including the kinetic type and parameters. In vitro human liver microsome incubation system was used. The Eadie-Hofstee plot was used to determine the kinetic type. The results showed that the data for human liver microsomes (HLMs) and monkey liver microsomes (MyLMs)-catalyzed glucuronidation were best fit to the substrate inhibition model. For the metabolism of TFP in HLMs, the kinetic parameters were calculated to be 40 ± 5 and 140 ± 20 µM for K m and K si values, respectively. For the MyLM-mediated metabolism of TFP, the K m and K si values were calculated to be 108 ± 10 and 250 ± 30 µM, respectively. The same metabolic kinetic type and different kinetic parameters were demonstrated for the metabolism of TFP between HLMs and MyLMs. All these data were helpful for understanding the metabolism difference of TFP between human and monkey.

[Economic analysis of health promotion conducted in an enterprise].

OBJECTIVE: To take intervention measures for health promotion after investigation of occupational health needs among employees, to analyze the economic input and output of the intervention measures, and to analyze the feasibility of health promotion through cost-effectiveness analysis and cost-benefit analysis. METHODS: A survey was conducted in an enterprise using a self-designed questionnaire to investigate the general information on enterprise, occupational history of each employee, awareness of occupational health knowledge, awareness of general health knowledge, awareness of hypertension, acquired immune deficiency syndrome, etc., lifestyle, and needs for health knowledge. Intervention measures were taken in the enterprise according to the investigation results, and then investigation and economic analysis of investment in health promotion, economic benefit, and absence of employees were performed using the questionnaire. RESULTS: After intervention, the awareness rate of the Code of Occupational Disease Prevention increased from 4.5% to 15.3%, the awareness rate of the definition of occupational diseases increased from 4.5% to 73.5%, and the awareness rate of the prevention and control measures for occupational diseases increased from 38.4% to 85.8%. Before intervention, 25.4%of all employees thought salt intake needed to be reduced, and this proportion increased to 92.5% after intervention. After the control strategy for health promotion, the benefit of health promotion that results from avoiding absence of employees and preventing occupational diseases was more than ten times the investment in health promotion, suggesting a significant benefit of health promotion conducted in the enterprise. CONCLUSION: The return on health promotion's investment for enterprise is worth. Health promotion really not just contribute to improve hygienic knowledge but increase the economic benefit.