Synthesis of 1-Benzyl-2,4-diarylimidazole through I2/CuI-Catalyzed Cyclization of Benzylamine and Hydrazone.

In this paper, we report an innovative method for synthesizing 1-benzyl-2,4-diarylimidazole utilizing 1-phenylethanone-2-(2-pyridinyl) hydrazine and benzylamine, catalyzed by an I2/CuI system. This approach represents a significant departure from traditional methods for synthesizing polysubstituted imidazoles; it employs the I2/CuI catalyst to replace rare metal catalysts, thereby achieving high yields of substitution products (≤85%). This method for the generation of 1,2,4-triimidazole derivatives is characterized by its exceptional chemical selectivity and extensive substrate compatibility.

Intercross population study reveals that co-mutation of mitfa genes in two subgenomes induces red skin color in common carp ( Cyprinus carpio wuyuanensis).

Common carp are among the oldest domesticated fish in the world. As such, there are many food and ornamental carp strains with abundant phenotypic variations due to natural and artificial selection. Hebao red carp (HB, Cyprinus carpio wuyuanensis), an indigenous strain in China, is renowned for its unique body morphology and reddish skin. To reveal the genetic basis underlying the distinct skin color of HB, we constructed an improved high-fidelity (HiFi) HB genome with good contiguity, completeness, and correctness. Genome structure comparison was conducted between HB and a representative wild strain, Yellow River carp (YR, C. carpio haematopterus), to identify structural variants and genes under positive selection. Signatures of artificial selection during domestication were identified in HB and YR populations, while phenotype mapping was performed in a segregating population generated by HB×YR crosses. Body color in HB was associated with regions with fixed mutations. The simultaneous mutation and superposition of a pair of homologous genes ( mitfa) in chromosomes A06 and B06 conferred the reddish color in domesticated HB. Transcriptome analysis of common carp with different alleles of the mitfa mutation confirmed that gene duplication can buffer the deleterious effects of mutation in allotetraploids. This study provides new insights into genotype-phenotype associations in allotetraploid species and lays a foundation for future breeding of common carp.

[Nuclear magnetic resonance-based metabolomics revealed metabolite profiles participate in intervention effect of refined moxibustion in gastric ulcer model rats].

OBJECTIVE: To investigate the effect of refined moxibustion on expression of gastric mucosal epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF), and changes of metabolite profiles in gastric ulcer (GU) rats, so as to analyze its mechanism underlying improvement of GU. METHODS: Male SD rats were randomized into control, model, acupoint moxibustion groups (n=6 per group). The GU model was induced by cold-restraint stress. The ignited refined moxa was applied to bilateral "Liangmen" (ST21) and "Zusanli" (ST36) for 3 cones/acupoint, once daily for 7 days. Then, we employed 1H NMR-based metabolomics approach to analyze the metabolic profiles of serum and stomach tissue samples. The conventional histopathological changes of the gastric mucosa were observed by H.E. stain and the expressions of EGFR and VEGF in the gastric mucosa were detected by immunohistochemistry. RESULTS: Compared to the control group, the expression levels of EGFR and VEGF were significantly increased in the model group (P<0.01, P<0.05), and further notably up-regulated in the acupoint moxibustion group (P<0.001, P<0.01). Results of H.E. staining showed damage of the folds of gastric mucosa, disordered arrangement of the glands, infiltration of inflammatory cells and unclear structure of gastric mucosa in the model group, which was relatively milder in the acupoint moxibustion group. 1H-NMR technical analysis showed that in comparison with the control group, 11 and 11 metabolites in the stomach extract and plasma were increased, 10 in the gastric tissue and 3 in the plasma were decreased in the GU model group; while in comparison with the model group, 17 differently expressed metabolites in the gastric extract and 10 metabolites in the plasma restored to their levels of control group after the acupoint moxibustion intervention. These metabolites participate in 12 metabolic pathways including glycine, serine and threonine metabolism, glutathione metabolism, glycine metabolism, alanine, aspartic acid and glutamic acid metabolism, purine metabolism, glyoxylic acid and digarboxylic acid metabolism, biosynthesis of aminoacyl-tRNA, amino sugar and nucleotide sugar metabolism, cysteine and methionine metabolism, citrate cycle, pyruvate metabolism, and the mutual conversion of pentose and glucuronate，suggesting their involvement in moxibustion-induced improvement of GU. CONCLUSION: Refined moxibustion at ST21 and ST36 can up-regulate the expression of EGFR and VEGF in the gastric mucosa and lessen gastric mucosal injury, which may be related to its effects in reducing GU-induced metabolic disorders, including sugar, purine, amino acid, and phospholipid metabolism and antioxidant defense system.

Role of TLR4/NF-κB Signalling Pathway in Pulmonary Arterial Hypertension in Patients with Chronic Obstructive Pulmonary Disease.

OBJECTIVE: To determine the role of toll-like receptor 4 (TLR4)/ nuclear factor kappa B (NF-κB) signalling pathway in pulmonary arterial hypertension (PAH) in patients with chronic obstructive pulmonary disease (COPD). STUDY DESIGN: An experimental study. PLACE AND DURATION OF STUDY: Department of Respiratory Disease, The Hospital Affiliated to Jiangnan University, Wuxi, Jiangsu, China, from June 2018 to December 2019. METHODOLOGY: Subjects included 98 COPD patients and 22 healthy individuals (control group). COPD patients were divided into two groups as PAH group (PAH group, n=57) and normal pulmonary arterial pressure group (nPAP group, n=41). TLR4 and NF-κB in peripheral blood mononuclear cells (PBMC) were measured by real-time polymerase chain reaction (RT-PCR); and inflammatory cytokine of IL-6 and TNF-α were estimated by enzyme-linked immunosorbent assay (ELISA) of three groups. RESULTS: The levels of TLR4, NF-κB and inflammatory cytokine of IL-6 and TNF-α of PAH group were higher than those in nPAP group and controls (all p<0.05); and controls had a lower levels of TLR4, NF-κB and TNF-α than those n PAP group patients (all p<0.05) except for PAP and IL-6 (p=0.121 and p=0.304, respectively). The expression levels of TLR4 and NF-κB in PBMC were positively related to that PAP and inflammatory cytokine of IL-6 and TNF-α in PAH patients with COPD (all p<0.05), but the positive correlation betweenIL-6 and TNF-α expression level was not established (p=0.170). All parameters in the nPAP group had no significant correlation to each other, it is the same in control (all p>0.05). CONCLUSIONS: Inflammatory mechanisms play an important role in the development of PAH in patients with COPD. TLR4/NF-κB signal transduction pathway is involved in the pathogenesis of PAH, and the expression levels of TLR4/NF-κB may reflect the severity of PAH in patients with COPD. Key Words: Toll-like receptor 4, Nuclear factor kappa B, Pulmonary arterial hypertension, Chronic obstructive pulmonary disease, Inflammatory cytokine.

Ultrasound-guided percutaneous microwave ablation for 755 benign breast lesions: a prospective multicenter study.

OBJECTIVES: To evaluate the clinical efficacy of microwave ablation (MWA) of benign breast lesions (BBLs) and compare the learning curves of international radiologists (IRs) and surgeons. METHODS: In total, 440 patients with 755 clinicopathologically confirmed BBLs from 5 centers were prospectively enrolled from February 2014 to July 2018. Technical success, complications, volume reduction ratio (VRR), palpability, and cosmetic satisfaction after ablation were analyzed. In addition, the ablation time (AT) and energy (AE) with the number of procedures were analyzed for learning curve evaluation. RESULTS: The mean maximum diameter was 1.7 ± 0.6 cm. The complete ablation rate reached 100%, including 45.8% lesions adjacent to the skin, pectoralis, or areola. After a median follow-up of 13.7 months, the 12-month VRR of all lesions was 97.9%, and that for 1.0- to 2.0-cm and ≥ 2.0-cm lesions was 98.6% and 96.9%, respectively. A total of 55.9% of BBLs became nonpalpable (palpable in 85.7% of cases before MWA) by both the clinician and patient. The cosmetic and minimally invasive satisfaction rates were good or excellent in 98.4% and 94.5% of patients, respectively. The median AT/cm3 and AE/cm3 decreased as experience increased. The AE/cm3 of the IR with 5 years of experience was lower than that of the IR with 1 year of experience and the surgeons, while the AT/cm3 of surgeons was comparable with that of the IR with 5 years of experience at relatively mature phase. CONCLUSIONS: Ultrasound-guided percutaneous MWA is a valuable technique for the treatment of BBLs. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02860104) KEY POINTS: • Ultrasound-guided percutaneous microwave ablation has the potential to become a valuable technique for the treatment of benign breast lesions. • A skilled interventional radiologist shows a rapid improvement in mastering the technique.

Effect of Moxibustion on Intestinal Microbiome in Acute Gastric Ulcer Rats.

In Traditional Chinese Medicine (TCM), moxibustion had been used for thousands of years. Many clinical case reports and scientific studies had proved that moxibustion had a good effect in treating acute gastric ulcer (AGU). Some studies had shown that the relative content and species of bacteria in the intestinal would be changed when gastric mucosal injury happened. However, there was little research on the effect of intestinal microbiome with AGU rats that were treating by moxibustion. This study is aimed at analyzing the effect of fecal microbiome in rats with AGU by the 16S rDNA sequencing technology. Male SD rats were established by orally feeding once with 70% ethanol at 4 ml/kg except the control group, then treated by moxibustion in the stomach meridian group ("Liangmen," "Zusanli") and the gallbladder meridian group ("Riyue," "Yanglingquan") for 5 days. The 16S rDNA sequencing technology analysis of feces combined with histopathological methods and molecular biological detection methods was used to evaluate the therapeutic mechanism of moxibustion on AGU. AGU brought cause changes in the number and species of intestinal bacteria. Moxibustion on stomach meridian group could reduce the area of gastric mucosal injury and regulate the relative content of GAS and EGF. Moreover, moxibustion on the stomach meridian group could increase the relative content and species of beneficial bacteria in the intestine of rats with AGU. The relative abundance of intestinal probiotics was significantly upregulated in Alphaproteobacteria, Actinomycetales, and Bacillales. In addition, moxibustion might promote the repair of gastric mucosal injury by increasing the number and species of beneficial bacteria in the intestine.

Population genetic analysis of aquaculture salmonid populations in China using a 57K rainbow trout SNP array.

Various salmonid species are cultivated in cold water aquaculture. However, due to limited genomic data resources, specific high-throughput genotyping tools are not available to many of the salmonid species. In this study, a 57K single nucleotide polymorphism (SNP) array for rainbow trout (Oncorhynchus mykiss) was utilized to detect polymorphisms in seven salmonid species, including Hucho taimen, Oncorhynchus masou, Salvelinus fontinalis, Brachymystax lenok, Salvelinus leucomaenis, O. kisutch, and O. mykiss. The number of polymorphic markers per population ranged from 3,844 (O. kisutch) to 53,734 (O. mykiss), indicating that the rainbow trout SNP array was applicable as a universal genotyping tool for other salmonid species. Among the six other salmonid populations from four genera, 28,882 SNPs were shared, whereas 525 SNPs were polymorphic in all four genera. The genetic diversity and population relationships of the seven salmonid species were studied by principal component analysis (PCA). The phylogenetic relationships among populations were analyzed using the maximum likelihood method, which indicated that the shared SNP markers provide reliable genomic information for population genetic analyses in common aquaculture salmonid fishes. Furthermore, this obtained genomic information may be applicable for population genetic evaluation, marker-assisted breeding, and propagative parent selection in fry production.

Ultrasound guided percutaneous microwave ablation of benign breast lesions.

The benign breast lesions (BBLs) share a high incidence for women and therapy methods with minimal invasion and better cosmetic outcome are thirsted for. In this study, 122 patients with 198 biopsy-proved BBLs were enrolled. Ultrasound (US)-guided microwave ablation (MWA) was performed with local anesthesia from November, 2013 to April, 2016. The mean longest tumor size assessed was 1.6±0.7 cm (ranging 0.7-4.9 cm). MWA was successfully performed in all cases including 85 lesions adjacent to the skin, pectoralis and areola. The mean ablation time was 3.2mins (ranging 0.5-18.3 mins). 99.5% of BBLs showed complete ablation when assessed by magnetic resonance imaging and 100% of them by US. At the median 14-month follow-up, the BBLs were not palpable in 45.9 % of the cases (palpable in 90.2 % of the cases before MWA) and the mean volume reduction ratio was 78.4±33.5% for total lesions and 89.3±20.8%, 84.7±27.6% and 55.9±32.9% for ≤1.0 cm, 1.1-2.0cm and >2.0 cm lesions in 12-month follow-up, respectively. Cosmesis were reported as good or excellent in 100 % by physician and patients. No side effect was found. The MWA of the BBLs proved feasible and effective, while showing meaningful reduction in volume, palpability and cosmetic satisfying outcomes.

Synthesis, Characterization and Antifungal Evaluation of Novel Thiochromanone Derivatives Containing Indole Skeleton.

Invasive fungal disease constitutes a growing health problem and development of novel antifungal drugs with high potency and selectivity against new fungal molecular targets are urgently needed. In order to develop potent antifungal agents, a novel series of 6-alkyl-indolo[3,2-c]-2H-thiochroman derivatives were synthesized. Microdilution broth method was used to investigate antifungal activity of these compounds. Most of them showed good antifungal activity in vitro. Compound 4o showed the best antifungal activity, which (inhibition of Candida albicans and Cryptococcus neoformans) can be achieved at the concentration of 4 µg/mL. Compounds 4b (inhibition of Cryptococcus neoformans), 4j (inhibition of Cryptococcus neoformans), 4d (inhibition of Candida albicans) and 4h (inhibition of Candida albicans) also showed the best antifungal activity at the concentrations of 4 µg/mL. The molecular interactions between 4o and the N-myristoyltransferase of Candida albicans (PDB ID: 1IYL) were finally investigated through molecular docking. The results indicated that these thiochromanone derivatives containing indole skeleton could serve as promising leads for further optimization as novel antifungal agents.

[Studies on chemical constituents of Valeriana plants and their biological activities].

The recent progresses on chemical components and pharmacological activities of the genus Valerianawere summarized.Besides-essential oil, the chemical composition of Valerianais mainly focused on monoterpenoids,sesquiterpenoids,lignans, flavonoids, alkaloids, etc. Iridoids are the main chemical components ofmonoterpenoids. There are two types ofiridoidson the basis of the cyclopentane open or not. The Valerianahas been drawmuch attention for their significant sedation,spasmolysis,antidepression,antitumor, against adenosine A1 receptors and cytotoxicityactivity,and had certain function for cardiovascular disease treatment. Given to the fact of the lack of systematic review and summary of studies on the Valeriana, we summarized and analyze the study literatures on the pharmacological activity of Valerianain recent years, and providedsome basisfor further study.

Hand-assisted laparoscopic versus open radical resection of gastric remnant cancer: a clinical comparison.

OBJECTIVE: To compare the perioperative clinical data between hand-assisted laparoscopic and open radical resection of gastric remnant cancer, and analyze the feasibility and advantages of hand-assisted laparoscopic resection of gastric remnant cancer. METHODS: The clinical data of 18 patients with gastric remnant cancer who underwent hand-assisted laparoscopic (n=9) or open surgery (n=9) were retrospectively analyzed to compare the perioperative outcomes and recovery between December 2007 and October 2014. RESULTS: All 18 patients underwent surgery without post-operative complications. In the hand-assisted laparoscopy group, none required conversion to open surgery, and no intraoperative auxiliary injury occurred. The incision length was (8.78±0.62) cm in the hand-assisted laparoscopy group, and (14.06±0.81) cm in the open surgery group (t=15.565, P=0.000). The duration of the operation averaged (221.11±19.48) min in the hand-assisted laparoscopy group, and (212.89±14.30) min in the open surgery group (t=-1.021, P=0.323). The intraoperative blood loss was (105.56±35.04) ml in the hand-assisted laparoscopy group, and (147.78±41.92) ml in the open surgery group (t=2.319, P=0.034). The number of lymph nodes scavenged was (16.22±2.99) and 16.67±3.28 in the hand-assisted laparoscopy group and in the open surgery group, respectively (t=-.300, P=0.768). The postoperative time to passage of gas by anus was (68.67±10.00) hr in the hand-assisted laparoscopy group, and (79.78±9.16) hr in the open surgery group (t=2.458, P=0.026). Mild postoperative hemorrhage occurred at the anastomotic site in one patient in each surgery group. These complications resolved after treatment. And no serious perioperative complications, such as anastomotic site fistula, massive hemorrhage in the peritoneal cavity or digestive tract or death occurred in either group. CONCLUSIONS: Hand-assisted laparoscopic radical resection of gastric remnant cancer is feasible, is of comparable efficacy to open surgery, and offers several advantages including small incisions, mild intraoperative hemorrhage, rapid postoperative recovery, and few postoperative complications.

Efficient synthesis of 2,3-disubstituted-2,3-dihydroquinazolin-4(1H)-ones catalyzed by dodecylbenzenesulfonic acid in aqueous media under ultrasound irradiation.

Synthesis of 2,3-disubstituted-2,3-dihydroquinazolin-4(1H)-one derivatives catalyzed by dodecylbenzenesulfonic acid was carried out in 80-92% yields at 40-42 °C within 1-2 h in aqueous media via one-pot three-component condensation of isatoic anhydride, aromatic aldehyde and amine under ultrasound irradiation. Convenient work-up procedures, mild reaction conditions, avoiding the use of organic solvents, and friendly to environment are the salient features of this protocol.

Synthesis of multisubstituted imidazoles via copper-catalyzed [3 + 2] cycloadditions.

A simple route for the synthesis of imidazole derivatives via copper-catalyzed [3 + 2] cycloaddition reaction is described. This strategy has achieved high regioselectivity and used oxygen as an oxidant without the addition of expensive catalysts to provide moderate to good yields.

An efficient synthesis of 2-substituted benzothiazoles in the presence of FeCl3/Montmorillonite K-10 under ultrasound irradiation.

2-Substituted benzothiazoles have been synthesized via one-pot reaction from aromatic aldehydes and o-aminothiophenol in the presence of FeCl(3)/Montmorillonite K-10 in absolute methanol at 25-30°C under ultrasound irradiation. The remarkable advantages are an inexpensive and easily available reagent, a simple procedure, mild conditions, short reaction times and moderate to good yields.

Dynamic changes of matrix metalloproteinases in rat liver during the development of diethylnitrosamine-induced hepatocarcinoma.

OBJECTIVE: To study the dynamic changes of matrix metalloproteinases (MMPs) in the liver of rat during experimental hepatocarcinogenesis. METHODS: Immunohistochemistry, gelatin zymography, and reverse transcriptase-PCR were used for detection of latent and active forms and mRNA of MMPs in each phases of carcinogenic stages. RESULTS: MMPs expression was detected in normal and cirrhotic liver, which was most obvious in the cancer cells after the development of hepatic carcinoma. Normal tissue showed only low levels of MMPs expression, which kept increasing in the course of hepatocarcinogenesis, as was also the case with the corresponding mRNA. CONCLUSION: Transcription and expression of MMPs keep increasing throughout the the process of hepatocarcinogenesis.