Enantioselective synthesis of chiral α,α-dialkyl indoles and related azoles by cobalt-catalyzed hydroalkylation and regioselectivity switch.

General, catalytic and enantioselective construction of chiral α,α-dialkyl indoles represents an important yet challenging objective to be developed. Herein we describe a cobalt catalyzed enantioselective anti-Markovnikov alkene hydroalkylation via the remote stereocontrol for the synthesis of α,α-dialkyl indoles and other N-heterocycles. This asymmetric C(sp3)-C(sp3) coupling features high flexibility in introducing a diverse set of alkyl groups at the α-position of chiral N-heterocycles. The utility of this methodology has been demonstrated by late-stage functionalization of drug molecules, asymmetric synthesis of bioactive molecules, natural products and functional materials, and identification of a class of molecules exhibiting anti-apoptosis activities in UVB-irradiated HaCaT cells. Ligands play a vital role in controlling the reaction regioselectivity. Changing the ligand from bi-dentate L6 to tridentate L12 enables CoH-catalyzed Markovnikov hydroalkylation. Mechanistic studies disclose that the anti-Markovnikov hydroalkylation involves a migratory insertion process while the Markovnikov hydroalkylation involves a MHAT process.

Circular RNA hsa_circ_0001846 facilitates the malignant behaviors of pancreatic cancer by sponging miR-204-3p and upregulating KRAS expression.

Pancreatic cancer (PC) is mainly derived from the exocrine pancreatic ductal epithelial cells, and it is strongly aggressive malignant tumor. Due to its insidious onset and the lack of effective diagnostic biomarkers, PC currently remains one of the main causes of cancer-related mortality worldwide. Recent studies have found that hsa_circ_0001846 is involved in the progression of multiple cancers and has the potential to become biomarkers, but its function and mechanism in PC remains unclear. We found by qRT-PCR experiments that hsa_circ_0001846 was upregulated in PC cells and tissues, while circBase, Sanger sequencing, agarose gel electrophoresis and FISH experiments identified the splicing site, ring structure and cellular localization of hsa_circ_0001846. Various functional experiments by using the construction of small interfering RNA targeting hsa_circ_0001846 and overexpression plasmid demonstrated that hsa_circ_0001846 promoted the proliferation, migration and invasion of PC cells. Moreover, the tumor weight and volume of nude mice were significantly reduced after the stable knockdown of hsa_circ_0001846. In the mechanism exploration, RNA pull-down experiments and dual-luciferase experiments helped us to determine that hsa_circ_0001846 regulated the KRAS expression by sponging miR-204-3p in PC, thus playing a pro-cancer role. In this study, the effect of miR-204-3p on PC was also explored for the first time, and we found that knockdown of miR-204-3p reversed the tumor suppressive effect caused by silencing hsa_circ_0001846, and silencing KRAS also rescued the pro-cancer effect caused by overexpression of hsa_circ_0001846. In conclusion, our study revealed the pro-cancer role of hsa_circ_0001846 in PC, and for the first time identified the mechanism that hsa_circ_0001846 regulated KRAS by sponging miR-204-3p to promote PC progression and had the potential to become a cancer biomarker.

Stevens-Johnson syndrome secondary to massive inflammatory hyperplasia of bilateral lingual margins: a case report and literature review.

Stevens-Johnson syndrome (SJS), also known as the multifactorial erythematous drug eruption, is a class of adverse reactions of the skin and mucous membranes primarily caused by drug allergy often involving the oral cavity, eyes, and external genital mucosa, generally accompanied by fever, and can be life-threatening in severe cases. In February 2022, the Department of Stomatology, the First Affiliated Hospital of Zhengzhou University admitted a patient with huge inflammatory hyperplasia of bilateral lingual margins secondary to SJS. Upon admission, no other obvious symptoms were observed except for tongue hyperplasia. The patient suffered from a severe adverse drug reaction caused by acetaminophen 2 months ago and was complicated by liver dysfunction and pulmonary infection. After 1 month of treatment and rehabilitation, he developed a secondary tongue mass and was subsequently admitted to Dept. of Oral and Maxillofacial Surgery Ward 2, the First Affiliated Hospital of Zhengzhou University. After completing the examination, the tongue mass was surgically removed. After a follow-up of 11 months, the patient's condition was satisfactory and no temporary discomfort was observed. The case of tongue mass secondary to SJS is extremely rare. If a stomatologist encounters a similar case, we should carefully inquire about the drug allergy history and recent medication history, and be alert to whether or not they had adverse drug reactions recently.

Radical-Based Convergent Paired Electrolysis.

Electrochemistry offers a sustainable platform for discovering reactions involving single-electron transfer (SET) that generates highly reactive and synthetically versatile radical species. Compared with photochemistry similarly specializing in SET which requires expensive photocatalysts, electrochemistry employs low-cost electricity to drive the electron flow. Paired electrolysis makes use of both half-reactions, thus obviating the need for sacrificial reactions and maximizing the atom and energy economy. In convergent paired electrolysis, anodic oxidation and cathodic reduction occur simultaneously to generate two intermediates, which are then coupled to furnish the product. It represents a distinctive approach to challenging redox-neutral reactions. However, the gap between the two electrodes makes it hard for a reactive intermediate to come across the other coupling partner. This concept article summarizes recent state-of-the-art advances on radical-based convergent paired electrolysis, which adopted different strategies to overcome the difficulty.

Diterpenoids inhibit ox-LDL-induced foam cell formation in RAW264.7 cells by promoting ABCA1 mediated cholesterol efflux.

Introduction: Atherosclerosis is the main cause of many cardiovascular diseases and contributes to morbidity and mortality worldwide. The formation of macrophage-derived foam cells plays a critical role in the early stage of atherosclerosis pathogenesis. Diterpenoids found in the flowers of Callicarpa rubella Lindl., a traditional Chinese medicine, have been reported to have anti-inflammatory activity. However, little is known about the effects of these diterpenoids on macrophage foam cell formation. Methods: A macrophage-derived foam cell formation model was established by treating RAW264.7 cells with oxidized low-density lipoprotein (ox-LDL) for 24 h. Oil red O staining were used to detect the intracellular lipids. The cholesterol efflux capacity was assayed by labeling cells with 22-NBD-cholesterol. Western blots and real-time PCRs were performed to quantify protein and mRNA expressions. Results: Two diterpenoid molecules, 14α-hydroxyisopimaric acid (C069002) and isopimaric acid (C069004), extracted from the flowers of Callicarpa rubella Lindl., significantly attenuated ox-LDL-induced foam cell formation in RAW264.7 macrophages. Further investigation showed that these two diterpenoids could promote cholesterol efflux from RAW264.7 macrophages to apolipoprotein A-I or high-density lipoproteins, which was associated with upregulated expression of ATP-binding cassette A1/G1 (ABCA1/G1), liver X receptor-α (LXRα), and peroxisome proliferator-activated receptor-γ (PPARγ). Unexpectedly, the diterpenoids C069002 and C069004 failed to enhance the mRNA transcription of the ABCG1 gene in macrophage-derived foam cells induced by ox-LDL. To evaluate the effects of diterpenoids on macrophage foam cell formation and determine the underlying mechanism, two drugs (lovastatin and rosiglitazone) were used as positive controls. Although both drugs could reduce macrophage foam cell formation and promote cholesterol efflux, they each had distinctive abilities to modulate the expression of cholesterol efflux-related genes. In contrast to lovastatin, rosiglitazone showed a similar influence on the expression of cholesterol efflux-related genes (including ABCA1, LXRα, and PPARγ) as the diterpenoids regardless of the presence or absence of ox-LDL, implying a similar mechanism by which they may exert atheroprotective effects. Conclusion: Our research indicates that diterpenoids effectively inhibit ox-LDL-induced macrophage foam cell formation by promoting cholesterol efflux from macrophages via the PPARγ-LXRα-ABCA1 pathway. Further investigation of diterpenoids as potential drugs for the treatment of atherosclerosis is warranted.

Genome-wide association studies of peduncle length in wheat under rain-fed and irrigating field conditions.

Drought is one of the most destructive environmental factors limiting wheat production and food security globally. Peduncle length (PLE) is an important morphological trait to determine plant architecture, photosynthate transport, and yield formation, which is also considered a useful index for drought tolerance in wheat. However, the genetic basis of wheat PLE is not well studied at present. Here, a large-scale genome-wide association study (GWAS) of PLE was performed using a panel of 282 wheat accessions with the Wheat 660K SNP array genotyping under rain-fed and irrigating field conditions. Totally, 1,301 significant marker-trait associations (MTAs) were identified using the threshold of p-value < 4.16 × 10-4, five of which were high-confidence. Furthermore, combining GWAS intervals, previously reported QTLs, expression levels, homologous genes, and selected sweep analysis, a total of 5 candidate genes were detected to associate with drought stress. Moreover, the expression levels of TraesCS2A02G082100 were significantly up-regulated under drought conditions and co-localized in the selected sweep region, suggesting it is a drought-responsive gene. Our results shed light on the genetic basis underlying wheat drought tolerance, which accelerates the marker-assistant selection and genetic improvement through genomic breeding in wheat.

Circular RNA hsa_circ_0007367 promotes the progression of pancreatic ductal adenocarcinoma by sponging miR-6820-3p and upregulating YAP1 expression.

Circular RNAs (circRNAs) play critical regulatory roles in cancer biological processes. Nevertheless, the contributions and underlying mechanisms of circRNAs to pancreatic ductal adenocarcinoma (PDAC) remain largely unexplored. Dysregulated circRNAs between cancerous tissues and matched adjacent normal tissues were identified by circRNA microarray in PDAC. The biological effect of hsa_circ_007367 both in vitro and in vivo was demonstrated by gain- and loss-of-function experiments. Further, dual-luciferase reporter and RNA pull-down assays were performed to confirm the interaction among hsa_circ_007367, miR-6820-3p, and Yes-associated protein 1 (YAP1). The expression of hsa_circ_007367 and YAP1 were detected by in situ hybridization (ISH) and immunohistochemistry (IHC) using tissue microarray (TMA) in 128 PDAC samples. We first identified that a novel circRNA, hsa_circ_0007367, was markedly upregulated in PDAC tissues and cells. Functionally, in vivo and in vitro data indicated that hsa_circ_0007367 promotes the proliferation and metastasis of PDAC. Mechanistically, we confirmed that hsa_circ_0007367 could facilitate the expression of YAP1, a well-known oncogene, by sponging miR-6820-3p, which function as a tumor suppresser in PDAC cells. The results of ISH and IHC demonstrated that hsa_circ_0007367 and YAP1 were upregulated in PDAC tissues. Furthermore, clinical data showed that higher hsa_circ_0007367 expression was correlated with advanced histological grade and lymph node metastasis in PDAC patients. In conclusion, our findings reveal that hsa_circ_0007367 acts as an oncogene via modulating miR-6820-3p/YAP1 axis to promote the progression of PDAC, and suggest that hsa_circ_0007367 may serve as a potential therapeutic target for treatment of PDAC.

Bio-inspired lanthanum-ortho-quinone catalysis for aerobic alcohol oxidation: semi-quinone anionic radical as redox ligand.

Oxidation reactions are fundamental transformations in organic synthesis and chemical industry. With oxygen or air as terminal oxidant, aerobic oxidation catalysis provides the most sustainable and economic oxidation processes. Most aerobic oxidation catalysis employs redox metal as its active center. While nature provides non-redox metal strategy as in pyrroloquinoline quinone (PQQ)-dependent methanol dehydrogenases (MDH), such an effective chemical version is unknown. Inspired by the recently discovered rare earth metal-dependent enzyme Ln-MDH, here we show that an open-shell semi-quinone anionic radical species in complexing with lanthanum could serve as a very efficient aerobic oxidation catalyst under ambient conditions. In this catalyst, the lanthanum(III) ion serves only as a Lewis acid promoter and the redox process occurs exclusively on the semiquinone ligand. The catalysis is initiated by 1e--reduction of lanthanum-activated ortho-quinone to a semiquinone-lanthanum complex La(SQ-.)2, which undergoes a coupled O-H/C-H (PCHT: proton coupled hydride transfer) dehydrogenation for aerobic oxidation of alcohols with up to 330 h-1 TOF.

Deviation Analyses of Computer-Assisted, Template-Guided Mandibular Reconstruction With Combined Osteotomy and Reconstruction Pre-Shaped Plate Position Technology: A Comparative Study.

BACKGROUND: Computer-assisted and template-guided mandibular reconstruction provides higher accuracy and less variation than conventional freehand surgeries. The combined osteotomy and reconstruction pre-shaped plate position (CORPPP) technique is a reliable choice for mandibular reconstruction. This study aimed to evaluate the accuracy of CORPPP-guided fibular flap mandibular reconstruction and analyze the possible causes of the deviations. PATIENTS AND METHODS: From June 2015 to December 2016, 28 patients underwent fibular flap mandibular reconstruction. Virtual planning and personalized CORPPP-guided templates were applied in 15 patients while 13 patients received conventional freehand surgeries. Deviations during mandibulectomy and fibular osteotomy, and overall and triaxial deviation of the corresponding mandibular anatomical landmarks were measured by superimposing the pre- and postoperative virtual models. RESULTS: The deviation of the resection line and resection angle was 1.23 ± 0.98 mm and 4.11° ± 2.60°. The actual length of fibula segments was longer than the designed length in 7 cases (mean: 0.35 ± 0.32 mm) and shorter in 22 cases (mean: 1.53 ± 1.19 mm). In patients without ramus reconstruction, deviations of the ipsilateral condylar head point (Co.), gonion point (Go.), and coracoid process point (Cor.) were 6.71 ± 3.42 mm, 5.38 ± 1.71 mm, and 11.05 ± 3.24 mm in the freehand group and 1.73 ± 1.13 mm, 1.86 ± 0.96 mm, and 2.54 ± 0.50 mm in the CORPPP group, respectively, with significant statistical differences (p < 0.05). In patients with ramus reconstruction, deviations of ipsilateral Co. and Go. were 9.79 ± 4.74 mm vs. 3.57 ± 1.62 mm (p < 0.05), and 15.17 ± 6.53 mm vs. 4.36 ± 1.68 mm (p < 0.05) in the freehand group and CORPPP group, respectively. CONCLUSION: Mandibular reconstructions employing virtual planning and personalized CORPPP-guided templates show significantly higher predictability, convenience, and accuracy of mandibular reconstruction compared with conventional freehand surgeries. However, more clinical cases were required for further dimensional deviation analysis. The application and exploration of clinical practice would also continuously improve the design of templates.

Mechanistic Studies on Bioinspired Aerobic C-H Oxidation of Amines with an ortho-Quinone Catalyst.

We report herein our mechanistic studies of the ortho-quinone-catalyzed aerobic oxidation of primary, secondary, and tertiary amines. Two different catalytic pathways were discovered for the reductive half reactions: for primary amines, the reaction was found to proceed via a transamination pathway, while the reactions with secondary amines and tertiary amines proceeded via hydride transfer. We also found that the amine substrates could significantly promote the regeneration of the ortho-quinone catalyst in the oxidative half reaction, in which a proton transfer occurs between the amine substrates and catechol derivatives (the reduced form of the ortho-quinone catalyst).

[Retrospective study on incomplete intestinal obstruction treated with the adjuvant therapy of acupuncture and moxibustion].

OBJECTIVE: To evaluate the clinical effects on incomplete intestinal obstruction treated with the adjuvant therapy of acupuncture and moxibustion. METHODS: Using the retrospective analysis, 80 patients of incomplete intestinal obstruction were divided into an observation group and a control group, 40 cases in each one. In the control group, the routine treatment was given, such as fasting, gastrointestinal decompression, parenteral nutrition, infection prevention with antibiotics and enema laxative. In the observation group, on the basis of the treatment as the control group, acupuncture was applied at bilateral Zusanli (ST 36), Shangjuxu (ST 37) and Xiajuxu (ST 39); moxibustion was used at left Yangchi (TE 4), Zhongwan (CV 12), Qihai (CV 6) and Guanyuan (CV 4). The treatment was given once a day, 30 min each time. The average days of treatment, the surgical transfer rate, the time to first flatus, the recovery time of defecation and the time of solid food intake were observed in the patients of the two groups. RESULTS: The average days of treatment in the observation group was obviously less than that in the control group (P<0.05). The surgical transfer rate in the observation group was obviously lower than that in the control group (P<0.05). The time to first flatus, the recovery time of defecation and the time of solid food intake were all obviously earlier than those in the control group (all P<0.05). CONCLUSION: The adjuvant therapy of acupuncture and moxibustion achieves the significant therapeutic effects on incomplete intestinal obstruction, shortens the treatment duration and reduces the surgical transfer rate and the patient's economic burden.

Oxidative Synthesis of Benzimidazoles, Quinoxalines, and Benzoxazoles from Primary Amines by ortho-Quinone Catalysis.

The bioinspired ortho-quinone catalysts have been applied to heterocycles synthesis. Without any metal cocatalysts, a sole ortho-quinone catalyst enables the oxidative synthesis of benzimidazoles, quinoxalines and benzoxazoles from primary amines in high yields under mild conditions with oxygen as the terminal oxidant.

[Canopy interception of sub-alpine dark coniferous communities in western Sichuan, China].

Based on field measurements of throughfall and stemflow in combination with climatic data collected from the meteorological station adjacent to the studied sub-alpine dark coniferous forest in Wolong, Sichuan Province, canopy interception of sub-alpine dark coniferous forests was analyzed and modeled at both stand scale and catchment scale. The results showed that monthly interception rate of Fargesia nitida, Bashania fangiana--Abies faxoniana old-growth ranged from 33% Grass to 72%, with the average of 48%. In growing season, there was a linear or powerful or exponential relationship between rainfall and interception an. a negative exponential relationship between rainfall and interception rate. The mean maximum canopy interception by the vegetation in the catchment of in.44 km was 1.74 ment and the significant differences among the five communities occurred in the following sequence: Moss-Fargesia nitida, Bashan afanglana-A. faxoniana stand > Grass-F. nitida, B. fangiana-A. faxoniana stand > Moss-Rhododendron spp.-A. faxoniana stand > Grass-Rh. spp.-A. faxoniana stand > Rh. spp. shrub. In addition, a close linear relationship existed between leaf area index (LAI) and maximum canopy interception. The simulated value of canopy interception rate, maximum canopy interception rate and addition interception rate of the vegetation in the catchment were 39%, 25% and 14%, respectively. Simulation of the canopy interception model was better at the overall growing season scale, that the mean relative error was 9%-14%.