Observation of Chiral Channels in Helical Covalent Organic Frameworks.

Unraveling the mechanism of chirality transfer across length scales is crucial to the rational development of functional materials with hierarchical chirality. The key obstacle is the lack of structural information, especially at the mesoscopic level. We report herein the structural identification of helical covalent organic frameworks (heliCOFs) with hierarchical chirality, which integrate molecular chirality, channel chirality, and morphology chirality into one crystalline entity. Specifically, benefiting from the highly ordered structure of heliCOFs, the existence of chiral channels at the mesoscopic level has been confirmed by electron crystallography, and the handedness of these chiral channels has been directly determined through the stereopair imaging technique. Accordingly, the chirality transfer in heliCOFs from microscopic to macroscopic levels could be rationalized with a layer-rotating model that has been supported by both crystal structure analysis and theoretical calculations. Observation of chiral channels in heliCOFs not only provides unprecedented data for the understanding of the chirality transfer process but also sheds new light on the rational construction of highly ordered polymeric materials with hierarchical chirality.

Cu-Catalyzed Regioselective C-H Amination of 2H-Indazoles for the Synthesis of Indazole-Containing Indazol-3(2H)-ones.

A copper-catalyzed C3 amination of 2H-indazoles with 2H-indazoles and indazol-3(2H)-ones under mild conditions was developed. A series of indazole-containing indazol-3(2H)-one derivatives were produced in moderate to excellent yields. The mechanistic studies suggest that the reactions probably proceed through a radical pathway.

Deoxyhypusine hydroxylase as a novel pharmacological target for ischemic stroke via inducing a unique post-translational hypusination modification.

Ischemic stroke remains one of the leading causes of death worldwide, thereby highlighting the urgent necessary to identify new therapeutic targets. Deoxyhypusine hydroxylase (DOHH) is a fundamental enzyme catalyzing a unique posttranslational hypusination modification of eukaryotic translation initiation factor 5A (eIF5A) and is highly involved in the progression of several human diseases, including HIV-1 infection, cancer, malaria, and diabetes. However, the potential therapeutic role of pharmacological regulation of DOHH in ischemic stroke is still poorly understood. Our study first discovered a natural small-molecule brazilin (BZ) with an obvious neuroprotective effect against oxygen-glucose deprivation/reperfusion insult. Then, DOHH was identified as a crucial cellular target of BZ using HuProt™ human proteome microarray. By selectively binding to the Cys232 residue, BZ induced a previously undisclosed allosteric effect to significantly increase DOHH catalytic activity. Furthermore, BZ-mediated DOHH activation amplified mitophagy for mitochondrial function and morphology maintenance via DOHH/eIF5A hypusination signaling pathway, thereby protecting against ischemic neuronal injury in vitro and in vivo. Collectively, our study first identified DOHH as a previously unreported therapeutic target for ischemic stroke, and provided a future drug design direction for DOHH allosteric activators using BZ as a novel molecular template.

Rutaecarpine Prevents High Glucose-Induced Endothelial Cell Senescence Through Transient Receptor Potential Vanilloid Subtype 1/ SIRT1 Pathway.

ABSTRACT: SIRT1 functions as a longevity factor to counteract vascular aging induced by high glucose. Our previous study revealed that rutaecarpine, the natural agonist of transient receptor potential vanilloid subtype 1 (TRPV1), prevented high glucose-induced endothelial dysfunction. The present study aims to evaluate the effects of rutaecarpine on endothelial cell senescence induced by high glucose, and focus on the regulatory effect on SIRT1 expression. In cultured human umbilical vein endothelial cell (HUVEC), exposure to 33 mM high glucose for 72 hours induced cellular senescence, demonstrated as cell cycle arrest at G0/G1 phase, decreased cell viability, and increased number of senescence-associated ß-galactosidase positive senescence cells and ROS production, which were effectively attenuated by treatment with rutaecarpine (0.3, 1, and 3 µM). Furthermore, rutaecarpine upregulated longevity protein SIRT1 expression in HUVECs, accompanied by decreased level of senescence marker p21. In addition, rutaecarpine increased intracellular calcium level in HUVECs, and pretreatment with TRPV1 antagonist capsazepine, intracellular Ca2+ chelator BAPTA-AM or CaM antagonist W-7 abolished the effects of rutaecarpine on SIRT1 expression. In summary, this study shows that rutaecarpine upregulates SIRT1 expression and prevents high glucose-induced endothelial cell senescence, which is related to activation of TRPV1/[Ca2+]i/CaM signal pathway. Our findings provide evidence that rutaecarpine may be a promising candidate with a novel mechanism in prevention vascular aging in diabetes.

Comparing the outcomes of bedside percutaneous VA-ECMO decannulation by ProGlide and Manta in a high-ECMO-volume center in Hong Kong.

BACKGROUND: The use of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) decannulation with different percutaneous closure devices has been increasing. At our center, ProGlide devices have been used since November 2018, and Manta devices became an alternative since March 2020. This study aimed to compare the success and complication rates and the clinical outcomes of ProGlide and Manta devices for VA-ECMO decannulation after arteriotomy wound closure. METHODS: We retrospectively reviewed the results of bedside VA-ECMO decannulation between November 2018 and June 2021. Patients with VA-ECMO who could be bridged to recovery were recruited and divided into the ProGlide or Manta group based on the closure device used. Procedure time, amount of blood loss, amount of blood products transfused, and use of vasoactive medications during the procedure were documented. Clinical examination and Doppler ultrasound were performed to detect any complications. RESULTS: After the closure technique, ProGlide was used in 44 patients and Manta was used in 13. There was no significant difference in the success rate between the ProGlide and Manta groups (86.4% vs. 100%). Amount of blood loss was greater in the ProGlide group than in the Manta group (290 [100-400] ml vs. 50 [50-100] ml), and more patients in the ProGlide group required an increased dose of inotropes during the procedure (59.1% vs. 15.4%), but the transfusion requirement was similar between the two groups. CONCLUSIONS: The success rate of hemostasis using arteriotomy wound closure during VA-ECMO decannulation was similar between the two devices.

Prothioconazole and prothioconazole-desthio induced different hepatotoxicities via interfering with glycolipid metabolism in mice.

Prothioconazole (PTA), a new triazole fungicide, has been widely used worldwide. A recent study has confirmed that PTA and its main metabolite prothioconazole-desthio (dPTA) interfere with the liver metabolism in reptiles. However, little is known about liver toxicity of these two pollutants in mammals. Here, female mice were orally exposed to PTA (1.5 mg/kg body weight/day) and dPTA (1.5 mg/kg body weight/day) for 30 days. Additionally, growth phenotype and indexes related to serum and liver function were examined. Using metabolomics and gene expression analysis, PTA- and dPTA-induced hepatotoxicity was studied to clarify its potential underlying mechanism of action. Together, the results indicated that PTA and dPTA exposure caused changes in growth phenotypes, including elevated blood glucose levels, triglyceride accumulation, and damage of liver function. Additionally, exposure to PTA and dPTA caused changes in genes and metabolites related to glycolipid metabolism in female mice, thereby interfering with the pyruvate metabolism and glycolysis/gluconeogenesis pathways, ultimately leading to hepatic metabolism disorders. In particular, the effect of dPTA on hepatotoxicity has been proven to be more significant than that of PTA. Thus, these findings help us understand the underlying mechanism of action of PTA and dPTA exposure-induced hepatotoxicity in mammals and possibly humans.

[Biomechanical Study of New Biodegradable Esophageal Stent].

The radial force of the degradable esophageal stent before and after degradation is one of the important indicators for effective treatment of esophageal stricture. Based on a combination of in vitro experiments and finite element analysis, this paper studies and verifies the biomechanical properties of a new type of degradable esophageal stent under different esophageal stricture conditions. Under radial extrusion conditions, the maximum stress at the port of the stent is 65.25 MPa, and the maximum strain is 1.98%; The peak values of stress and strain under local extrusion and plane extrusion conditions both appear in the extrusion area and the compression expansion area at both ends, which are respectively 48.68 MPa, 46.40 MPa, 0.49%, 1.13%. The maximum radial force of the undegraded stent was 11.22 N, and 97% and 51% of the maximum radial force were maintained after 3 months and 6 months of degradation, respectively. The research results verify the safety and effectiveness of the radial force of the new degradable esophageal stent, and provide a theoretical basis for the clinical treatment of esophageal stricture.

Lowering the Contact Barriers of 2D Organic F16 CuPc Field-Effect Transistors by Introducing Van der Waals Contacts.

2D organic crystals exhibit efficient charge transport and field-effect characteristics, making them promising candidates for high-performance nanoelectronics. However, the strong Fermi level pinning (FLP) effect and large Schottky barrier between organic semiconductors and metals largely limit device performance. Herein, by carrying out temperature-dependent transport and Kelvin probe force microscopy measurements, it is demonstrated that the introducing of 2D metallic 1T-TaSe2 with matched band-alignment as electrodes for F16 CuPc nanoflake filed-effect transistors leads to enhanced field-effect characteristics, especially lowered Schottky barrier height and contact resistance at the contact and highly efficient charge transport within the channel, which are attributed to the significantly suppressed FLP effect and appropriate band alignment at the nonbonding van der Waals (vdW) hetero-interface. Moreover, by taking advantage of the improved contact behavior with 1T-TaSe2 contact, the optoelectronic performance of F16 CuPc nanoflake-based phototransistor is drastically improved, with a maximum photoresponsivity of 387 A W-1 and detectivity of 3.7 × 1014 Jones at quite a low Vds of 1 V, which is more competitive than those of the reported organic photodetectors and phototransistors. The work provides an avenue to improve the electrical and optoelectronic properties of 2D organic devices by introducing 2D metals with appropriate work function for vdW contacts.

[Total flavonoids of Drynariae Rhizoma regulates ER-p38 MAPK signaling pathway to improve scopolamine-induced learning and memory impairments in model mice].

This study intended to explore the effect and mechanism of total flavonoids of Drynariae Rhizoma in improving scopola-mine-induced learning and memory impairments in model mice. Ninety four-month-old Kunming(KM) mice were randomly divided into six groups. The ones in the model group and blank group were treated with intragastric administration of normal saline, while those in the medication groups separately received the total flavonoids of Drynariae Rhizoma, Kangnaoshuai Capsules, donepezil, as well as total flavonoids of Rhizoma Drynariae plus estrogen receptor(ER) blocker by gavage. The mouse model of learning and memory impairments was established via intraperitoneal injection of scopolamine. Following the measurement of mouse learning and memory abilities in Morris water maze test, the hippocampal ERß expression was detected by immunohistochemistry, and the expression levels of ERß and phosphorylated p38(p-p38) in the hippocampus and B-cell lymphoma 2(Bcl-2), Bcl-2-associated death promoter(Bad), and cysteinyl aspartate-specific protease-3(caspase-3) in the apoptotic system were assayed by Western blot. The contents of malondia-ldehyde(MDA), superoxide dismutase(SOD), and nitric oxide(NO) in the hippocampus were then determined using corresponding kits. Compared with the control group, the model group exhibited significantly prolonged incubation period, reduced frequency of cros-sing the platform, shortened residence time in the target quadrant, lowered ERß, Bcl-2 and SOD activity in the hippocampus, and increased p-p38/p38, Bad, caspase-3, MDA, and NO. Compared with the model group, the total flavonoids of Rhizoma Drynariae increased the expression of ERß and SOD in the hippocampus, down-regulated the expression of neuronal pro-apoptotic proteins, up-re-gulated the expression of anti-apoptotic proteins, and reduced p-p38/p38, MDA, and NO. The effects of total flavonoids of Drynariae Rhizoma on the above indexes were reversed by ER blocker. It has been proved that the total flavonoids of Drynariae Rhizoma obviously alleviate scopolamine-induced learning and memory impairments in mice, which may be achieved by regulating the neuronal apoptotic system and oxidative stress via the ER-p38 mitogen-activated protein kinase(ER-p38 MAPK) signaling pathway.

Prevalence and Clinical Significance of Portal Vein Thrombosis in Patients With Cirrhosis and Acute Decompensation.

BACKGROUND & AIMS: Portal vein thrombosis (PVT) is a common and serious complication in patients with cirrhosis. However, little is known about PVT in patients with cirrhosis and acute decompensation (AD). We investigated the prevalence and clinical significance of PVT in nonmalignant patients with cirrhosis and AD. METHODS: We performed a retrospective study of 2 cohorts of patients with acute exacerbation of chronic liver disease who participated in the Chinese AcuTe on CHronic LIver FailurE study, established by the Chinese Chronic Liver Failure Consortium, from January 2015 through December 2016 (n = 2600 patients) and July 2018 through January 2019 (n = 1370 patients). We analyzed data on the prevalence, clinical manifestations, and risk factors of PVT from 2826 patients with cirrhosis, with and without AD. RESULTS: The prevalence of PVT in patients with cirrhosis and AD was 9.36%, which was significantly higher than in patients with cirrhosis without AD (5.24%) (P = .04). Among patients with cirrhosis and AD, 63.37% developed PVT recently (the first detected PVT with no indication of chronic PVT). Compared with patients without PVT, a significantly higher proportion of patients with PVT had variceal bleeding (47.33% vs 19.63%; P < .001) and patients with PVT had a significantly higher median serum level of D-dimer (2.07 vs 1.25; P < .001). Splenectomy and endoscopic sclerotherapy were independent risk factors for PVT in patients with cirrhosis and AD. The 1-year mortality rate did not differ significantly between patients with vs without PVT. CONCLUSIONS: In an analysis of data from 2826 patients with cirrhosis, a significantly higher proportion of those with AD had PVT than those without AD. PVT was associated with increased variceal bleeding, which would increase the risk for AD. Strategies are needed to prevent PVT in patients with cirrhosis, through regular screening, to reduce portal hypertension. ClinicalTrials.gov no: NCT02457637 and NCT03641872.

Isosibiricin inhibits microglial activation by targeting the dopamine D1/D2 receptor-dependent NLRP3/caspase-1 inflammasome pathway.

Microglia-mediated neuroinflammation is a crucial risk factor for neurological disorders. Recently, dopamine receptors have been found to be involved in multiple immunopathological processes and considered as valuable therapeutic targets for inflammation-associated neurologic diseases. In this study we investigated the anti-neuroinflammation effect of isosibiricin, a natural coumarin compound isolated from medicinal plant Murraya exotica. We showed that isosibiricin (10-50 µM) dose-dependently inhibited lipopolysaccharide (LPS)-induced BV-2 microglia activation, evidenced by the decreased expression of inflammatory mediators, including nitrite oxide (NO), tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1ß (IL-1ß) and interleukin-18 (IL-18). By using transcriptomics coupled with bioinformatics analysis, we revealed that isosibiricin treatment mainly affect dopamine receptor signalling pathway. We further demonstrated that isosibiricin upregulated the expression of dopamine D1/2 receptors in LPS-treated BV-2 cells, resulting in inhibitory effect on nucleotide binding domain-like receptor protein 3 (NLRP3)/caspase-1 inflammasome pathway. Treatment with dopamine D1/2 receptor antagonists SCH 23390 (1 µM) or sultopride (1 µM) could reverse the inhibitory effects of isosibiricin on NLRP3 expression as well as the cleavages of caspase-1 and IL-1ß. Collectively, this study demonstrates a promising therapeutic strategy for neuroinflammation by targeting dopamine D1/2 receptors.

Comprehensive assessment of deceased donor kidneys with clinical characteristics, pre-implant biopsy histopathology and hypothermic mechanical perfusion parameters is highly predictive of delayed graft function.

Background: Due to the current high demand for transplant tissue, an increasing proportion of kidney donors are considered extended criteria donors, which results in a higher incidence of delayed graft function (DGF) in organ recipients. Therefore, it is important to fully investigate the risk factors of DGF, and establish a prediction system to assess donor kidney quality before transplantation.Methods: A total of 333 donation after cardiac death kidney transplant recipients were included in this retrospective study. Both univariate and multivariate analyses were used to analyze the risk factors of DGF occurrence. Receiver operating characteristic (ROC) curves were used to analyze the predictive value of variables on DGF posttransplant.Results: The donor clinical scores, kidney histopathologic Remuzzi scores and hypothermic mechanical perfusion (HMP) parameters (flow and resistance index) were all correlated. 46 recipients developed DGF postoperatively, with an incidence of 13.8% (46/333). Multivariate logistic regression analysis of the kidney transplants revealed that the independent risk factors of DGF occurrence post-transplantation included donor score (OR = 1.12, 95% CI 1.06-1.19, p < 0.001), Remuzzi score (OR = 1.21, 95% CI 1.02-1.43, p = 0.029) and acute tubular injury (ATI) score (OR = 4.72, 95% CI 2.32-9.60, p < 0.001). Prediction of DGF with ROC curve showed that the area under the curve was increased to 0.89 when all variables (donor score, Remuzzi score, ATI score and HMP resistance index) were considered together.Conclusions: Combination of donor clinical information, kidney pre-implant histopathology and HMP parameters provide a more accurate prediction of DGF occurrence post-transplantation than any of the measures alone.

[Regulatory effect of Jinkui Shenqi Pills on the gene expression of the Nrf2 signaling pathway in cyclophosphamide-induced testis injury in mice].

OBJECTIVE: To investigate the protective effect of Jinkui Shenqi Pills (JSP) against cyclophosphamide-induced testis injury (TI) and its anti-oxidation mechanism in mice. METHODS: Thirty male mice were equally divided into a blank control, a TI model control and a JSP treatment group. The mice in the JSP treatment group were treated intragastrically with JSP and the blank controls with normal saline at 1.2 g/kg qd for 7 days, and then the animals in both the TI model control and JSP treatment groups were injected intraperitoneally with cyclophosphamide at 50 mg/kg, once a week, for 35 days, to induce testis injury. After modeling, all the mice were weighed and sacrificed, followed by detection of the serum T content, measurement of the testis weight, examination of semen parameters in the caudad epididymis, and determination of the levels of super oxide dismutase (SOD) and malondialdehyde (MDA) in the testis tissue and the expressions of relevant genes by qRT-PCR. RESULTS: The mice of the TI model control group, compared with the blank controls, showed significant decreases in the body weight (ï¼»34.63 ± 1.92ï¼½ vs ï¼»48.32 ± 1.64ï¼½ g, P<0.05), testis weight (ï¼»80.00 ± 3.90ï¼½ vs ï¼»140.00 ± 6.10ï¼½ mg, P<0.05), testicular organ coefficient (ï¼»0.22 ± 0.01ï¼½ vs ï¼»0.31 ±0.03ï¼½%, P<0.05), sperm motility (ï¼»48.66 ± 8.08ï¼½% vs ï¼»89.33 ± 4.04ï¼½%, P<0.05), sperm concentration (ï¼»28.42 ± 5.26ï¼½ vs ï¼»77.67 ± 8.73ï¼½ ×106/ml, P<0.05), and levels of serum T (ï¼»8.75 ± 0.96ï¼½ vs ï¼»21.75 ± 1.71ï¼½ pg/ml, P<0.05) and SOD (ï¼»140.82 ± 10.08ï¼½ vs ï¼»358.52 ± 40.41ï¼½ U/mg prot, P<0.05), but remarkable increases in the sperm deformity rate (ï¼»37.33 ± 2.08ï¼½ vs ï¼»15.33±1.53ï¼½%, P<0.05) and MDA level (ï¼»54.89±6.09ï¼½ vs ï¼»30.21±2.17ï¼½ nmol/ng prot, P<0.05). The mice of the JSP treatment group, in comparison with the TI model controls, exhibited markedly increased body weight (ï¼»39.80±2.89ï¼½ vs ï¼»34.63±1.92ï¼½g, P<0.05), testis weight (ï¼»130.00 ± 11.00ï¼½ vs ï¼»80.00 ± 3.90ï¼½ mg, P<0.05), testicular organ coefficient (ï¼»0.28 ± 0.01ï¼½ vs ï¼»0.22 ± 0.01ï¼½%, P<0.05), sperm motility (ï¼»76.00 ± 5.29ï¼½% vs ï¼»48.66 ± 8.08ï¼½%, P<0.05), sperm concentration (ï¼»56.08 ± 4.29ï¼½ vs ï¼»28.42 ± 5.26ï¼½ ×106/ml, P<0.05), and levels of serum T (ï¼»15.50 ± 1.29ï¼½ vs ï¼»8.75 ± 0.96ï¼½ pg/ml, P<0.05) and SOD (ï¼»206.59 ± 16.38ï¼½ vs ï¼»140.82 ± 10.08ï¼½ U/mg prot, P<0.05), but decreased sperm deformity rate (ï¼»25.01 ± 2.99ï¼½% vs ï¼»37.33 ± 2.08ï¼½%, P<0.05) and MDA level (ï¼»35.84 ± 3.61ï¼½ vs ï¼»54.89 ± 6.09ï¼½ nmol/ng prot, P<0.05). The mRNA expressions of NOQ-1, Nrf2 and HO-1 in the testis tissue were significantly lower and that of Caspase-3 remarkably higher in the TI model control than in the blank control group (P<0.05), while those of Nrf2 and HO-1 significantly higher and that of Caspase-3 markedly lower in the JSP treatment group than in the TI model controls (P<0.05). Histopathological images displayed reduced layers of spermatogenic cells in the seminiferous tubules, complete exfoliation of the spermatogenic cells in some of the tubules and decreased number of sperm cells in the TI model controls, which were all found normal in the JSP treatment group. CONCLUSIONS: Jinkui Shenqi Pills can effectively inhibit cyclophosphamide-induced testis injury, which may be related to its effect of regulating the gene expression of the Nrf2 signaling pathway and enhancing the activity of antioxidant enzymes.

[Method for active ingredients' in vivo target identification of traditional Chinese medicine using magnetic nanoparticles].

Target identification is an important prerequisite for the study of medicine action mechanism. Currently,drug target identification is mostly based on various cell models in vitro. However,the growth microenvironment,nutrition metabolism,biological properties as well as functions are quite different between in vitro cell culture and physiological environment in vivo; wherefore,it is a challenging scientific issue to establish an effective method for identifying drug targets in vivo condition. In this study,we successfully prepared a kind of magnetic nanoparticles( MNPs) which can be chemically modified by the hydroxyl structure of natural bioactive compound echinacoside( ECH) via the epoxy group label on the surface of MNPs. Therefore,organ-selective and recoverable nanoscale target-recognizing particles were prepared. We then intravenously injected the ECH-binding MNPs into rats and distributed them to specific organs in vivo. After cell endocytosis,ECH-binding MNPs captured target proteins in situ for further analysis. Based on this method,we discovered several potential target proteins in the spleen lysates for ECH,and preliminarily clarified the immuno-regulation mechanism of ECH. Collectively,our strategy developed a proof-of-concept technology using nanoparticles for in vivo target identification,and also provided a feasible approach for drug target prediction and pharmacological mechanism exploration.

Acute-on-Chronic Liver Failure in China: Rationale for Developing a Patient Registry and Baseline Characteristics.

Definitions and descriptions of acute-on-chronic liver failure (ACLF) vary between Western and Eastern types, and alcoholism and hepatitis B virus (HBV) are, respectively, the main etiologies. To determine whether there are unified diagnostic criteria and common treatment programs for different etiologies of ACLF, a multicenter prospective cohort with the same inclusion criteria and disease indicators as those used in the European Consortium Acute-on-Chronic Liver Failure in Cirrhosis Study is urgently needed in Asia, where the prevalence of HBV is high. A multicenter prospective cohort of 2,600 patients was designed, drawing from 14 nationwide liver centers from tertiary university hospitals in China, and 2,600 hospitalized patients with chronic liver disease (both cirrhotic and noncirrhotic) of various etiologies with acute decompensation or acute hepatic injury were continuously recruited from January 2015 to December 2016. Data were collected during hospitalization, and follow-ups were performed once a month, with plans to follow all patients until 36 months after hospital discharge. Of these patients, 1,859 (71.5%) had HBV-related disease, 1,833 had cirrhotic disease, and 767 had noncirrhotic disease. The numbers and proportions of enrolled patients from each participating center and the baseline characteristics of the patients with or without cirrhosis are presented.

Outcomes for primary kidney transplantation from donation after Citizens' death in China: a single center experience of 367 cases.

BACKGROUND: The cases of donation after brain death followed by circulatory death (DBCD) and donation after cardiac death (DCD) have been increased year by year in China. Further research is needed to understand in the outcomes and risk factors of delayed graft function (DGF) in order to minimize the risk of DGF and ameliorate its potential impact on long-term outcomes. This study was to explore the differences in outcomes between DBCD and DCD transplant and the main risk factors for DGF in DBCD. METHODS: Retrospective analysis of the clinical data of 367donations after citizens' death kidney transplant procedures (donors and recipients) between July 2012 and August 2015 at our center. RESULTS: During the study period, the donation success rate was 25.3%. 164 cases of DBCD and 35 cases of DCD had been implemented and 367 kidneys were transplanted. The incidence of DGF in DBCD group were significantly lower than that of DCD group (12.0% vs. 27.0%, p = 0.002). The 1-year percent freedom from acute rejection (AR) was significantly higher in DBCD group compared with it of DCD group (94% vs. 82%, p = 0.036). Multivariate logistic regression analysis of the kidney transplants revealed that the high risk factors for DGF after renal transplantation in DBCD were history of hypertension (Odds Ratio [OR] = 5.88, 95% CI: 1.90 to 18.2, p = 0.002), low blood pressure (BP < 80 mmHg) (OR = 4.86, 95% CI: 1.58 to 14.9, p = 0.006) and serum creatinine of donor (OR = 1.09, 95% CI: 1.03 to 1.16, p = 0.003) before donation. CONCLUSIONS: The outcomes of DBCD could be better than DCD in DGF and AR. The main risk factors for DGF in DBCD kidney transplants are donors with a history of hypertension, low blood pressure, and serum creatinine of donor before donation.

Visible-Light Induced Direct Synthesis of Polysubstituted Furans from Cyclopropyl Ketones.

In this article, a photoredox protocol for the synthesis of furans via oxidative coupling of olefin generated in situ from cyclopropyl ketones with ketonic oxygen atom is presented. Moreover, bromination of furans in the presence of overstoichiometric oxidant has been achieved with high regioselectivity.

Rutaecarpine Reverses the Altered Connexin Expression Pattern Induced by Oxidized Low-density Lipoprotein in Monocytes.

Adhesion of monocytes to the vascular endothelium is crucial in atherosclerosis development. Connexins (Cxs) which form hemichannels or gap junctions, modulate monocyte-endothelium interaction. We previously found that rutaecarpine, an active ingredient of the Chinese herbal medicine Evodia, reversed the altered Cx expression induced by oxidized low-density lipoprotein (ox-LDL) in human umbilical vein endothelial cells, and consequently decreases the adhesive properties of endothelial cells to monocytes. This study further investigated the effect of rutaecarpine on Cx expression in monocytes exposed to ox-LDL. In cultured human monocytic cell line THP-1, ox-LDL rapidly reduced the level of atheroprotective Cx37 but enhanced that of atherogenic Cx43, thereby inhibiting adenosine triphosphate release through hemichannels. Pretreatment with rutaecarpine recovered the expression of Cx37 but inhibited the upregulation of Cx43 induced by ox-LDL, thereby improving adenosine triphosphate-dependent hemichannel activity and preventing monocyte adhesion. These effects of rutaecarpine were attenuated by capsazepine, an antagonist of transient receptor potential vanilloid subtype 1. The antiadhesive effects of rutaecarpine were also attenuated by hemichannel blocker 18α-GA. This study provides additional evidence that rutaecarpine can modulate Cx expression through transient receptor potential vanilloid subtype 1 activation in monocytes, which contributes to the antiadhesive properties of rutaecarpine.

Phenolic Compounds from Clinopodium chinense (Benth.) O. Kuntze and Their Inhibitory Effects on α-Glucosidase and Vascular Endothelial Cells Injury.

Following an in vitro bioactivity-guided fractionation procedure, 14 compounds including eight flavonoids and six phenylpropanoids were isolated and identified from the AcOEt fraction of Clinopodium chinense (Benth.) O. Kuntze. All constituents were tested for α-glucosidase and high glucose-induced injury in human umbilical vein endothelial cells (HUVECs) inhibitory activities. All constituents exhibited varying degrees α-glucosidase inhibitory activity and protective activity on HUVECs. Among them, luteolin (2), eriodictyol (5), ethyl rosmarinate (13), and clinopodic acids B (14) were proved to be potent α-glucosidase inhibitors with IC50 value ranging from 0.6 to 2.0 µm. Additionally, luteolin (2), naringenin (4), eriodictyol (5), ethyl (2R)-3-(3, 4-dihydroxyphenyl)-2-hydroxypropanate (9), caffeic acid (11), ethyl rosmarinate (13), and clinopodic acids B (14) significantly ameliorate HUVECs injury induced by high glucose with an approximate EC50 value of 3 - 36 µm. These results suggest that the 14 bioactive constituents were responsible for hypoglycemic and protective vascular endothelium effect of C. chinense (Benth.) O. Kuntze and their structure-activity relationship was also analyzed briefly. Eriodictyol, luteolin, ethyl rosmarinate, and clinopodic acids B were the potential lead compounds of antidiabetic drugs.

Influence of de novo donor-specific antibody on early renal allograft function recovery.

BACKGROUND: The aim of the present study is to investigate the impact of de novo donor-specific antibodies (dnDSA) on early graft function, to provide objective reference for early clinical diagnosis and reasonable individualized treatment. METHODS: 305 cases of renal transplant patients for the first time were observed in this study. Follow-up time for all recipients was 6 months after operation. HLA antibody, DSA, renal function were monitored after transplant. RESULTS: In total of 305 cases, 66 cases (21.64%) were HLA antibody positive and 21 cases (6.89%) showed acute rejection (AR) in 6 months after transplant. The HLA antibody-positive patients included six cases of dnDSA-positive and 60 cases of dnDSA-negative. The incidence of AR was 2.09% (5/239) in HLA antibody-negative patients, 18.33% (11/60) in HLA antibody positive with DSA-negative patients, and 83.33% (5/6) in HLA antibody-positive patients with DSA-positive. There was a big difference between DSA-negative and DSA-positive patients (p < 0.01). The recovery time of AR patients with DSA-positive were longer than DSA-negative patients, and the recovery graft function of AR patient with DSA-positive were not as good as those with DSA-negative. CONCLUSIONS: The appearance of dnDSA in the early stage of kidney transplantation is a warning sign of AR occurrence. Dynamic monitoring of HLA antibody and DSA could predict the state of graft function, and play an important role in the prevention of AR, timely and effectively.