Stereoselective Synthesis of Cyclohepta[b]indoles by Visible-Light-Induced [2+2]-Cycloaddition/retro-Mannich-type Reactions.

A novel method for the concise synthesis of cyclohepta[b]indoles in high yields was developed. The method involves a visible-light-induced, photocatalyzed [2+2]-cycloaddition/ retro-Mannich-type reaction of enaminones. Experimental and computational studies suggested that the reaction is a photoredox process initiated by single-electron oxidation of an enaminone moiety, which undergoes subsequent cyclobutane formation and rapidly fragmentation in a radical-cation state to form cyclohepta[b]indoles.

Baicalein attenuates cardiac hypertrophy in mice via suppressing oxidative stress and activating autophagy in cardiomyocytes.

Baicalein is a natural flavonoid extracted from the root of Scutellaria baicalensis that exhibits a variety of pharmacological activities. In this study, we investigated the molecular mechanisms underlying the protective effect of baicalein against cardiac hypertrophy in vivo and in vitro. Cardiac hypertrophy was induced in mice by injection of isoproterenol (ISO, 30 mg·kg-1·d-1) for 15 days. The mice received caudal vein injection of baicalein (25 mg/kg) on 3rd, 6th, 9th, 12th, and 15th days. We showed that baicalein administration significantly attenuated ISO-induced cardiac hypertrophy and restored cardiac function. The protective effect of baicalein against cardiac hypertrophy was also observed in neonatal rat cardiomyocytes treated with ISO (10 µM). In cardiomyocytes, ISO treatment markedly increased reactive oxygen species (ROS) and inhibited autophagy, which were greatly alleviated by pretreatment with baicalein (30 µM). We found that baicalein pretreatment increased the expression of catalase and the mitophagy receptor FUN14 domain containing 1 (FUNDC1) to clear ROS and promote autophagy, thus attenuated ISO-induced cardiac hypertrophy. Furthermore, we revealed that baicalein bound to the transcription factor FOXO3a directly, promoting its transcription activity, and transactivated catalase and FUNDC1. In summary, our data provide new evidence for baicalein and FOXO3a in the regulation of ISO-induced cardiac hypertrophy. Baicalein has great potential for the treatment of cardiac hypertrophy.

High repetitive arginine in the anterior of PCV3 capsid protein is a severe obstacle for its expression in E. coli.

Porcine circovirus type 3 (PCV3) is a novel circovirus identified in sows with PDNS-like clinical signs and reproductive failure. The capsid protein (CAP) of PCV3 is expected to be an effective vaccine candidate. Here, we expressed the original capsid protein, truncated capsid protein without anterior highly repetitive arginine (ΔCAP) and their codon-optimized counterparts in E. coli. These results showed that lots of repeated arginine could severely lower the expression of PCV3 capsid protein in E. coli. At the same time, the recombined truncated PCV3 capsid protein forms typic virions. The efficient expression of capsid protein is expected to serve the development of PCV3 vaccines and other studies of PCV3 capsid protein.

Underlying IgM heavy chain amyloidosis in treatment-refractory IgA nephropathy: A case report.

BACKGROUND: Monoclonal immunoglobulin can cause renal damage, with a wide spectrum of pathological changes and clinical manifestations without hematological evidence of malignancy. These disorders can be missed, especially when combined with other kidney diseases. CASE SUMMARY: A 61-year-old woman presented with moderate proteinuria with normal renal function. She was diagnosed with IgA nephropathy combined with monoclonal gammopathy of undetermined significance after the first renal biopsy. Although having received immunosuppressive treatment for 3 years, the patient developed nephrotic syndrome. Repeated renal biopsy and laser microdissection/mass spectrometry analysis confirmed heavy chain amyloidosis. After nine cycles of bortezomib, cyclophosphamide and dexamethasone, she achieved very good partial hematological and kidney responses. CONCLUSION: Renal injury should be monitored closely in monoclonal gammopathy patients without obvious hematological malignancy, especially in patients with other pre-existing renal diseases.

Predictors of Short-term Outcomes of Patients with Peritoneal Dialysis-associated Peritonitis.

Objective To investigate the risk factors predicting the short-term outcomes of patients with peritoneal dialysis(PD)-associated peritonitis (PDAP). Methods In this retrospective cohort study,the clinical data at baseline and 0-3 months before peritonitis onset (peritonitis-free period) were collected from end-stage renal disease patients who started PD and suffered from PDAP between January 1,2004 and March 31,2017 in Peking Union Medical College Hospital. After 4 weeks of follow-up,these patients were divided into two groups according to the clinical outcomes,namely poor outcome group and good outcome group. Characteristics at baseline and before peritonitis were compared. Risk factors associated with short-term outcomes were also analyzed. Results Totally 162 PDAP patients were enrolled,among whom 55 (34.0%) experienced adverse outcomes and 107 (66.0%) had good outcome. At baseline,the proportion of clinical atherosclerotic vascular disease was significantly higher in poor outcome group than in good outcome group (49.1% vs. 31.8%;χ2=4.639,P=0.031),whereas indicators were comparable (all P>0.05). During the peritonitis-free period,significantly higher level of high-sensitivity C-reactive protein (hsCRP) [9.3(2.2,16.3)mg/dl vs. 3.6(1.4,9.5)mg/dl,Z=-2.879,P=0.004],higher proportion of low transport type of peritoneum function (8.7% vs. 1.0%;Z=4.879,P=0.027),and lower creatinine clearance rate [56.7 (45.7,71.1) ml/(min·w·1.73 m2)vs. 61.4 (54.5,76.4) ml/(min·w·1.73 m2);Z=-2.084,P=0.037] were observed in poor outcome group. Univariate Logistic regression analysis showed the combination of clinical atherosclerotic vascular disease (OR=2.070,95%CI:1.062-4.034,P=0.033) and higher hsCRP before peritonitis (OR=1.032,95%CI:1.001-1.059,P=0.015) were the risk factors of short-term poor outcome in PDAP patients. Multivariate Logistic regression analysis showed that,after the gender,age at peritonitis,PD duration,diabetes,and serum albumin before peritonitis were adjusted,higher hsCRP before peritonitis (OR=1.026,95%CI:1.000-1.052,P=0.046) and comorbidity of clinical atherosclerotic vascular disease (OR=2.105,95% CI:1.014-4.367,P=0.046) were the independent risk factors for the poor outcomes in PDAP patients. Conclusion Higher pre-peritonitis hsCRP and comorbidity of clinical atherosclerotic vascular disease at baseline may predict poor short-term outcomes in PDAP patients.

Effectiveness of Peritoneal Dialysis in Treating Adult End Stage Renal Disease Patients with Polycystic Kidney Disease.

Objective To observe the clinical characteristics,dialysis modalities,and outcomes of end stage renal disease(ESRD)patients with polycystic kidney disease(PKD)and to evaluate the feasibility of peritoneal dialysis in these population. Methods The clinical data of ESRD patient whose primary diagnosis was PKD in Peking Union Medical College Hospital were retrospectively collected from January 1993 to December 2015.PKD patients were divided into two groups according to dialysis modality,namely peritoneal dialysis group(PKD-PD)group and hemodialysis(PKD-HD)group.In addition,we randomly chose non-PKD patients from 622 peritoneal dialysis patients who were matched with PKD-PD patients in age,gender and dialysis time.The primary end point was death.The survival rate was calculated by Kaplan-Meier analysis and the risk factors for suivival were analyzed by Cox regression model. Results Totally 47 PKD patients were enrolled,including 33 patients in PKD-PD group and 14 patients in PKD-HD group,and 42 non-PKD patients as the control group.The average age of PKD patients was(53±11)years,of which 38.3% were women.When compared with PKD-HD group,no significant difference in age,gender,comorbidities,kidney size,and residual glomerular filtration rate were observed in PKD-PD patients at baseline(all P>0.05).The average time on dialysis of PKD-PD patients was(36.2±33.1)months.The weekly urea clearance index(Kt/V)and weekly creatinine clearance were similar to non-PKD-PD group at 3 months,1 year,3 years,and 5 years(all P>0.05).The peritonitis rate was 1 episode/84.5 months.The survival rates at 1 year,3 years,and 5 years of PKD-PD group were 85.7%,78.6%,and 78.6%,which were similar to non-PKD-PD group and PKD-HD group respectively(all P>0.05).Multivariate Cox regression analysis showed that neither PKD nor PD independently predicted the mortality. Conclusion PD can be an option for ESRD patients with PKD.

Pedobacter zeae sp. nov., an endophytic bacterium isolated from maize root.

A novel Gram-staining-negative, aerobic, non-motile by gliding and rod-shaped strain, designated 22T, was isolated from surface-sterilized root tissue of maize planted in the Fangshan District of Beijing, PR China. The highest levels of 16S rRNA gene sequence similarity were found with respect to Pedobacter suwonensis 15-52T (97.5 %), Pedobacter terrae DS-57T (97.1 %) and Pedobacter alluvionis NWER-II11T (97.0 %). Phylogenetic analysis based on 16S rRNA gene sequence data indicated that strain 22T is a member of the genus Pedobacter. The isolate exhibited relatively low levels of DNA-DNA relatedness with respect to P. suwonensis DSM 18130T (21.3±2.0 %), P. alluvionis DSM 19624T (38.1±1.8 %) and P. terrae DSM 17933T (17.1±1.4 %). The DNA G+C content was 41.2±0.5 mol%. The major isoprenoid quinone was menaquinone-7 (MK-7). The major component in the polyamine pattern was sym-homospermidine. The major polar lipids consisted of phosphatidylethanolamine, three unidentified aminolipids and one unidentified lipid. The major fatty acids were identified as iso-C15 : 0 and summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c). The results of the physiological and biochemical tests and minor differences in the fatty acid profiles allowed a clear phenotypic differentiation of strain 22T from the related species with high 16S rRNA gene sequence similarity, P. suwonensis DSM 18130T, P. alluvionis DSM 19624T and P. terrae DSM 17933T. Strain 22T represents a novel species within the genus Pedobacter, for which the name Pedobacter zeae sp. nov. is proposed, with the type strain 22T (=CGMCC 1.15287T=DSM 100774T).

[Study on Total Triterpenoids Content of Enrichment Mineral Elements of Inonotus Obliquus].

Objective: To study the influence of different mineral elements enrichment of calcium, iron, and zinc on the growth of the mycelium from Inonotus obliquus, to explore the influence on total triterpenoids content of Inonotus obliquus. Methods: Mineral elements were enriched on Inonotus obliquus, total triterpenoids extraction methods and determination methods were optimized, and total triterpenoids content of Inonotus obliquus were compared through different mineral elements enrichment. Results: The mycelial growth and yield were promoted obviously when 1 000 mg/L Ca(NO3)2 was added in the culture medium, and the calcium enrichment rate could reach to 0.07%. The most appropriate iron source was Fe2(SO4)3, and the iron enrichment rate could reach to 0.29% when 300 mg/L Fe2(SO4)3 was added. 175 mg/L Zn SO4 led to the strongest mycelium growth vigor, and the zinc enrichment rate could reach to 0.57%. The total triterpenoids content of Inonotus obliquus was the highest (0.058 mg/mL) as enrichment of calcium element, the total triterpenoids content of Inonotus obliquus was the least (0.04 mg/mL) as enrichment of iron elements. Conclusion: The total triterpenoids content of Inonotus obliquus was the highest when calcium element was enriched. This study provides a new method and basic data for the factory production of Inonotus obliquus.

MicroRNA-29a Promotes Pancreatic Cancer Growth by Inhibiting Tristetraprolin.

BACKGROUND/AIMS: The microRNA (miR) 29 family has been studied extensively for its involvement in several diseases, and aberrant expression of its members is associated with tumorigenesis and cancer progression. Here, we examined the role of miR-29a in pancreatic cancer and the involvement of tristetraprolin (TTP). METHODS: We monitored miR-29a and TTP expression in pancreatic cancer by qRT-PCR and western blotting. The effect of miR-29a on pancreatic cancer was determined through MTT assay and migration assay. The results were validated in the tumorigenesis model. RESULTS: We found that miR-29a was up regulated in pancreatic tumor tissues and cell lines and positively correlated with metastasis. Ectopic expression of miR-29a increased the expression of pro-inflammatory factors and epithelial-mesenchymal transition (EMT) markers, through down regulating TTP. TTP was down regulated in tumor tissues, and its ectopic expression decreased cell viability and migration in vitro, inhibited tumor growth and the EMT phenotype in vivo, and reversed the effect of miR-29a on tumor cell proliferation and invasion in vitro and in vivo. CONCLUSION: Our results suggest that miR-29a acts as an oncogene by down regulating TTP and provide the basis for further studies exploring the potential of miR-29a and TTP as biomarkers and targets for the treatment of pancreatic cancer.

[Storage and allocation of carbon and nitrogen in Pinus tabuliformis plantations on the south slope of the East Qinling Mountains, China].

The objective of this study was to study carbon and nitrogen storages and distributions in Pinus tabuliformis plantations along an age chronosequence of 8-, 25-, 35-, 42- and 61-year-old on the south slope of the East Qinling Mountains; China. Results showed that the carbon content and nitrogen contents ranged from 441.40 to 526.21 g . kg-1 and from 3.13 to 3.99 g . kg-1 in arbor layer, from 426.06 to 447.25 g . kg-1 and from 10.62 to 12.45 g . kg-1 in shrub layer, from 301.37 to 401.52 g . kg-1 and from 10.35 to 13.33 g kg-1 in herb layer, from 382.83 to 424.71 g . kg-1, and from 8.69 to 11.90 g . kg-1 in litter layer, and from 1.51 to 18.17 g . kg-1 and from 0.29 to 1.45 g . kg-1 in soil layer (0-100 cm) , respectively. The largest carbon and nitrogen storages in arbor layer were trunks and branches, which made up 48.5% to 62.7% and 39.2% to 48.4% of the total storage, respectively. Carbon and nitrogen storages of P. tabuliformis plantations were obviously age-dependent. Carbon storage at first increased with stand Age before the stand was ripe. It was the highest (146.06 t . hm-2) when the stand was 35 year-old, after which the carbon storage de- creased. The nitrogen storage reached the peak value of 10.99 t . hm-2 at 25 year-old. The average carbon and nitrogen storages were 45.33 t . hm-2 and 568.55 kg . hm-2 in the plant layer and, 73.12 and 8.57 t . hm-2 in soil layer, respectively. Moreover, carbon and nitrogen were accumulated at higher levels in the surface soil layer. In addition, the storages of carbon and nitrogen were mainly distributed in soil layer and arbor layer in this region. The average carbon storage in different components followed an order as soil layer (64.1%) > arbor layer (30.0%) > shrub-herb and litter layers (5.9%), while the nitrogen storage followed as: soil layer (93.2%) > arbor layer (5.3%) > shrub-herb and litter layers (1.5%).

Percutaneous needle decompression in treatment of malignant small bowel obstruction.

AIM: To investigate the efficacy and safety of percutaneous needle decompression in the treatment of malignant small bowel obstruction (MSBO). METHODS: A prospective analysis of the clinical data of 52 MSBO patients undergoing percutaneous needle decompression was performed. RESULTS: Percutaneous needle decompression was successful in all 52 patients. Statistically significant differences were observed in symptoms such as vomiting, abdominal distension and abdominal pain before and after treatment (81.6% vs 26.5%, 100% vs 8.2%, and 85.7% vs 46.9%, respectively; all P < 0.05). The overall significantly improved rate was 19.2% (11/52) and the response rate was 94.2% (49/52) using decompression combined with nasal tube placement, local arterial infusion of chemotherapy and nutritional support. During the one-month follow-up period, puncture-related complications were acceptable. CONCLUSION: Percutaneous needle intestinal decompression is a safe and effective palliative treatment for MSBO.

[Risk factors of post-renal biopsy bleeding].

OBJECTIVE: To evaluate the risk factors of post-renal biopsy bleeding (PBB). METHODS: We retrospectively analyzed the clinical data of 1 262 patients who received ultrasound-guided biopsy of native kidney at our hospital from January 2005 to December 2006. RESULTS: The overall incidence of PBB was 30.3% (383/1,262), among which the incidence of hematoma was 29.4% (371/1,262) (the percentages of less and more than 5cm were 73.9% and 26.1%, respectively) while that of gross hematuria was only 1.3% (17/1,262). The incidences of minor, intermediate, and major bleeding complications were 21.4% (270/1,262), 8.4% (106/1,262), and 0.6% (7/1,262), respectively. In seven patients with major bleeding complications, six had renal disease secondary to rheumatic disease (lupus nephritis, n = 5; scleroderma crisis, n = 1), while the other one had IgA nephropathy (Lee's classification V). The risk of PBB was relatively higher in women and younger patients. CONCLUSIONS: Patients with chronic connective tissue diseases are vulnerable to severe PBB complications. A close monitoring of these patients is necessary.