Novel nano-drug delivery system for natural products and their application.

The development of natural products for potential new drugs faces obstacles such as unknown mechanisms, poor solubility, and limited bioavailability, which limit the broadened applicability of natural products. Therefore, there is a need for advanced pharmaceutical formulations of active compounds or natural products. In recent years, novel nano-drug delivery systems (NDDS) for natural products, including nanosuspensions, nanoliposomes, micelle, microemulsions/self-microemulsions, nanocapsules, and solid lipid nanoparticles, have been developed to improve solubility, bioavailability, and tissue distribution as well as for prolonged retention and enhanced permeation. Here, we updated the NDDS delivery systems used for natural products with the potential enhancement in therapeutic efficiency observed with nano-delivery systems.

[Analysis of the Current Application Status for Clinical and Home Monitoring of Obstructive Sleep Apnea-Hypopnea Syndrome].

The study provides an overview of the development status of sleep disorder monitoring devices. Currently, polysomnography (PSG) is the gold standard for diagnosing sleep disorders, necessitating multiple leads and requiring overnight monitoring in a sleep laboratory, which can be cumbersome for patients. Nevertheless, the performance of PSG has been enhanced through research on sleep disorder monitoring and sleep staging optimization. An alternative device is the home sleep apnea testing (HSAT), which enables patients to monitor their sleep at home. However, HSAT does not attain the same level of accuracy in sleep staging as PSG, rendering it inappropriate for screening individuals with asymptomatic or mild obstructive sleep apnea-hypopnea syndrome (OSAHS). The study suggests that establishing a Chinese sleep staging database and developing home sleep disorder monitoring devices that can serve as alternatives to PSG will represent a future development direction.

PRMT5 activates KLF5 by methylation to facilitate lung cancer.

The highly expressed oncogenic factor Krüppel-like factor 5 (KLF5) promotes various cancerous processes, such as cell growth, survival, anti-apoptosis, migration and metastasis, particularly in lung cancer. Nevertheless, the modifications to KLF5 after translation are poorly understood. Protein arginine methyltransferase 5 (PRMT5) is considered as an oncogene known to be involved in different types of carcinomas, including lung cancer. Here, we show that the expression levels of PRMT5 and KLF5 are highly expressed lung cancer. Moreover, PRMT5 interacts with KLF5 and facilitates the dimethylation of KLF5 at Arginine 41 in a manner that depends on methyltransferase activity. Downregulation or pharmaceutical suppression of PRMT5 reduces the expression of KLF5 and its downstream targets both in vitro and in vivo. Mechanistically, the dimethylation of KLF5 by PRMT5 promotes the maintenance and proliferation of lung cancer cells at least partially by stabilising KLF5 via regulation of the Akt/GSK3ß signalling axis. In summary, PRMT5 methylates KLF5 to prevent its degradation, thereby promoting the maintenance and proliferation of lung cancer cells. These results suggest that targeting PRMT5/KLF5 axis may offer a potential therapeutic strategy for lung cancer.

Analysis of cuproptosis-related lncRNA signature for predicting prognosis and tumor immune microenvironment in pancreatic cancer.

Pancreatic cancer (PC) is a highly malignant digestive tract tumor, with a dismal 5-year survival rate. Recently, cuproptosis was found to be copper-dependent cell death. This work aims to establish a cuproptosis-related lncRNA signature which could predict the prognosis of PC patients and help clinical decision-making. Firstly, cuproptosis-related lncRNAs were identified in the TCGA-PAAD database. Next, a cuproptosis-related lncRNA signature based on five lncRNAs was established. Besides, the ICGC cohort and our samples from 30 PC patients served as external validation groups to verify the predictive power of the risk signature. Then, the expression of CASC8 was verified in PC samples, scRNA-seq dataset CRA001160, and PC cell lines. The correlation between CASC8 and cuproptosis-related genes was validated by Real-Time PCR. Additionally, the roles of CASC8 in PC progression and immune microenvironment characterization were explored by loss-of-function assay. As showed in the results, the prognosis of patients with higher risk scores was prominently worse than that with lower risk scores. Real-Time PCR and single cell analysis suggested that CASC8 was highly expressed in pancreatic cancer and related to cuproptosis. Additionally, gene inhibition of CASC8 impacted the proliferation, apoptosis and migration of PC cells. Furthermore, CASC8 was demonstrated to impact the expression of CD274 and several chemokines, and serve as a key indicator in tumor immune microenvironment characterization. In conclusion, the cuproptosis-related lncRNA signature could provide valuable indications for the prognosis of PC patients, and CASC8 was a candidate biomarker for not only predicting the progression of PC patients but also their antitumor immune responses.

How to handle a delayed or missed dose of edoxaban in patients with non-valvular atrial fibrillation? A model-informed remedial strategy.

AIMS: Edoxaban is a non-vitamin K antagonist oral anticoagulant (NOAC) widely used for the long-term prevention of stroke in patients with non-valvular atrial fibrillation (NVAF). Adherence to NOAC therapy has been unsatisfactory and decreases over time. Remedial strategies are currently used to address the non-adherence events. Current recommendations, however, are generic and not well supported by evidence. The aim of this study was to explore appropriate remedial dosing regimens for non-adherent edoxaban-treated NVAF patients through Monte Carlo simulation. METHODS: Six regimens were compared with the current recommendations of the European Heart Rhythm Association (EHRA) guide based on total deviation time. Both edoxaban plasma concentration and intrinsic Factor Xa activity were considered. Monte Carlo simulations were performed using RxODE based on a published population pharmacokinetic/pharmacodynamic (PK/PD) model. RESULTS: The proposed remedial strategies were different than the EHRA recommendations and were related to the delay time. However, it was found that the missed dose can be administered immediately if the delay time is within 11 h. When the delay is between 12 and 19 h, a half dose followed by a regular dosing schedule is recommended. When the delay time exceeds 19 h, a full dose followed by a half dose is preferred. CONCLUSION: PK/PD modelling and simulation are effective in developing and evaluating the remedial strategies of edoxaban, which can help maximise its therapeutic effect.

Sinomenine ameliorates collagen-induced arthritis in mice by targeting GBP5 and regulating the P2X7 receptor to suppress NLRP3-related signaling pathways.

Sinomenine (SIN) is an isoquinoline alkaloid isolated from Sinomenii Caulis, a traditional Chinese medicine used to treat rheumatoid arthritis (RA). Clinical trials have shown that SIN has comparable efficacy to methotrexate in treating patients with RA but with fewer adverse effects. In this study, we explored the anti-inflammatory effects and therapeutic targets of SIN in LPS-induced RAW264.7 cells and in collagen-induced arthritis (CIA) mice. LPS-induced RAW264.7 cells were pretreated with SIN (160, 320, 640 µM); and CIA mice were administered SIN (25, 50 and 100 mg·kg-1·d-1, i.p.) for 30 days. We first conducted a solvent-induced protein precipitation (SIP) assay in LPS-stimulated RAW264.7 cells and found positive evidence for the direct binding of SIN to guanylate-binding protein 5 (GBP5), which was supported by molecular simulation docking, proteomics, and binding affinity assays (KD = 3.486 µM). More importantly, SIN treatment markedly decreased the expression levels of proteins involved in the GBP5/P2X7R-NLRP3 pathways in both LPS-induced RAW264.7 cells and the paw tissue of CIA mice. Moreover, the levels of IL-1ß, IL-18, IL-6, and TNF-α in both the supernatant of inflammatory cells and the serum of CIA mice were significantly reduced. This study illustrates a novel anti-inflammatory mechanism of SIN; SIN suppresses the activity of NLRP3-related pathways by competitively binding GBP5 and downregulating P2X7R protein expression, which ultimately contributes to the reduction of IL-1ß and IL-18 production. The binding specificity of SIN to GBP5 and its inhibitory effect on GBP5 activity suggest that SIN has great potential as a specific GBP5 antagonist.

[Clinical management of skin necrosis after penis lengthening surgery: Report of 12 cases].

OBJECTIVE: To analyze the causes of skin necrosis after penis lengthening surgery and corresponding treatment measures, and observe the clinical effect of free skin graft repair in the treatment of penile skin defects. METHODS: We retrospectively analyzed the clinical data on 12 cases of extensive penile skin necrosis and defect after penis lengthening surgery performed in our department from January 2017 to January 2022. The patients underwent free skin graft repair with medium- or full-thickness skin grafts from the thigh after wound preparation. RESULTS: The skin grafts survived well in all the 12 patients and the incisions healed in the first stage without any complications. At 6 months after surgery, skin sensation was mostly recovered in the area of penis skin grafting, no obvious skin ulceration or edema was observed, and the appearance of the penis was satisfactory. The IIEF-5 scores, Erectile Hardness Scale (EHS) scores, and the results of penile hardness tests of the patients all indicated normal erectile function. CONCLUSION: Free skin graft repair with autologous medium- or full-thickness skin grafts is a safe and effective surgical option for extensive penile skin necrosis after penis lengthening surgery.

A van der Waals Integrated Damage-Free Memristor Based on Layered 2D Hexagonal Boron Nitride.

2D materials with intriguing properties have been widely used in optoelectronics. However, electronic devices suffered from structural damage due to the ultrathin materials and uncontrolled defects at interfaces upon metallization, which hindered the development of reliable devices. Here, a damage-free Au/h-BN/Au memristor is reported using a clean, water-assisted metal transfer approach by physically assembling Au electrodes onto the layered h-BN which minimized the structural damage and undesired interfacial defects. The memristors demonstrate significantly improved performance with the coexistence of nonpolar and threshold switching as well as tunable current levels by controlling the compliance current, compared with devices with evaporated contacts. The devices integrated into an array show suppressed sneak path current and can work as both logic gates and latches to implement logic operations allowing in-memory computing. Cross-sectional scanning transmission electron microscopy analysis validates the feasibility of this nondestructive metal integration approach, the crucial role of high-quality atomically sharp interface in resistive switching, and a direct observation of percolation path. The underlying mechanism of boron vacancies-assisted transport is further supported experimentally by conductive atomic force microscopy free from process-induced damage, and theoretically by ab initio simulations.

Orelabrutinib-bruton tyrosine kinase inhibitor-based regimens in the treatment of central nervous system lymphoma: a retrospective study.

BACKGROUND: Central nervous system lymphoma (CNSL) is an aggressive lymphoma. Orelabrutinib, an oral Bruton tyrosine kinase inhibitor, is a new treatment strategy for CNSL. This study aims to evaluate the efficacy and safety of orelabrutinib-based regimens in the treatment of patients with CNSL. METHODS: Twenty-three patients with CNSL were included in this retrospective study. All patients received the orelabrutinib-based regimen. Efficacy was evaluated based on investigators' assessment of overall response rate (ORR), complete response/unconfirmed complete response (CR/CRu), partial response (PR), stable disease (SD), progressive disease (PD), duration of response (DOR), progression-free survival (PFS) and overall survival (OS). The safety of orelabrutinib-based regimens has also been evaluated. RESULTS: A total of 17.39% of patients received orelabrutinib-based regimens for consolidation therapy, and 82.61% of patients for induction therapy (4 newly diagnosed CNSL, 15 relapsed/refractory CNSL). In the newly diagnosed CNSL group, the ORR was 100% (1 CR, 1 CRu, 2 PR). The 6-month DOR rate, 6-month PFS rate, and 6-month OS rate were 100%, 100%, and 100%, respectively. Of the 15 relapsed/refractory CNSL patients, five therapy regimens were applied (orelabrutinib, n = 3; orelabrutinib/immunotherapy, n = 3; orelabrutinib/chemotherapy, n = 2; orelabrutinib/immunochemotherapy, n = 6; orelabrutinib/radiotherapy, n = 1). The ORR was 60.00% (4 CR, 5 PR). The 6-month DOR rate, 6-month PFS rate, and 6-month OS rate were 92.30%, 67.70%, and 70.00%, respectively. Twenty-one patients reported adverse events (AEs), and 6 patients experienced grade ≥ 3 AEs. CONCLUSION: Orelabrutinib-based regimens were efficacious and well-tolerated in patients with CNSL. These combined therapies offer a new potential therapeutic strategy for patients with CNSL.

The Establishment of China Bronchiectasis Registry and Research Collaboration (BE-China): Protocol of a prospective multicenter observational study.

BACKGROUND: Bronchiectasis is a highly heterogeneous chronic airway disease with marked geographic and ethnic variations. Most influential cohort studies to date have been performed in Europe and USA, which serve as the examples for developing a cohort study in China where there is a high burden of bronchiectasis. The Establishment of China Bronchiectasis Registry and Research Collaboration (BE-China) is designed to: (1) describe the clinical characteristics and natural history of bronchiectasis in China and identify the differences of bronchiectasis between the western countries and China; (2) identify the risk factors associated with disease progression in Chinese population; (3) elucidate the phenotype and endotype of bronchiectasis by integrating the genome, microbiome, proteome, and transcriptome with detailed clinical data; (4) facilitate large randomized controlled trials in China. METHODS: The BE-China is an ongoing prospective, longitudinal, multi-center, observational cohort study aiming to recruit a minimum of 10,000 patients, which was initiated in January 2020 in China. Comprehensive data, including medical history, aetiological testing, lung function, microbiological profiles, radiological scores, comorbidities, mental status, and quality of life (QoL), will be collected at baseline. Patients will be followed up annually for up to 10 years to record longitudinal data on outcomes, treatment patterns and QoL. Biospecimens, if possible, will be collected and stored at - 80 °C for further research. Up to October 2021, the BE-China has enrolled 3758 patients, and collected 666 blood samples and 196 sputum samples from 91 medical centers. The study protocol has been approved by the Shanghai Pulmonary Hospital ethics committee, and all collaborating centers have received approvals from their local ethics committee. All patients will be required to provide written informed consent to their participation. CONCLUSIONS: Findings of the BE-China will be crucial to reveal the clinical characteristics and natural history of bronchiectasis and facilitate evidence-based clinical practice in China. Trial registration Registration Number in ClinicalTrials.gov: NCT03643653.

Modification of Pyrrolo[2,1-a]isoquinolines and Pyrrolo[1,2-a]quinolines with Ammonium Acetate and Dimethyl Sulfoxide via Methylthiomethylation.

An efficient methylthiomethylation of pyrroloisoquinolines and pyrroloquinolines has been reached by the use of ammonium acetate and dimethyl sulfoxide. Methylthiomethylated heterocycles can be obtained in moderate to good yields in most cases, while trace amounts to good yields of methylene-bridged products can be observed. Choice of DMSO activator and its amount have a great influence on the chemoselectivity of this process. It is worth noting that this process can also be scalable. Another feature of this process is that the product can be transformed to sulfone and sulfoxide easily.

[Seminal vesiculoscopy: Safe and effective for the treatment of refractory hemospermia].

OBJECTIVE: To investigate the clinical effect and safety of transutricular seminal vesiculoscopy in the treatment of refractory hemospermia. METHODS: Using 6Fr ureteroscopy through the prostatic utricle, we treated 103 cases of refractory hemospermia with distal seminal duct obstructive lesions, including 12 cases complicated by distal seminal duct cyst. We rinsed the seminal duct cavity, cleaned out the stones, removed the cyst wall with holmium laser and followed up the patients for 12 months postoperatively. RESULTS: The operations were successfully completed in all the cases but 1 (0.9%), in which the ureteroscope failed to enter the bilateral seminal vesicles. The operation time was (47 ± 9) min. No rectal injury or acute epididymitis occurred intraoperatively, nor fever, long-term dysuria or long-term hematuria after surgery. Postoperative follow-up showed that bloody semen symptoms vanished in 93 (90.3%) of the cases, improved significantly in 4 (3.9%) and not significantly in 2 (1.9%), and 3 cases of recurrence (2.9%) were all relieved after reoperation. CONCLUSION: Transutricular seminal vesiculoscopy has the advantages of clear anatomic vision, minor invasiveness and significant effectiveness in the treatment of refractory hemospermia. What's more, holmium laser is better than plasmakinetic resection in removal of the cyst wall.

Formylation and Bromination of Pyrrolo[2,1-a]isoquinoline Derivatives with Bromoisobutyrate and Dimethyl Sulfoxide.

We have developed an efficient formylation of pyrroloisoquinolines using bromoisobutyrate and dimethyl sulfoxide as carbonyl reagent. Various formylated pyrroloisoquinolines could be prepared in good yields (up to 94%). This formylation process can be easily scaled up to gram scale with good yield. In most cases of pyrroloisoquinolines without methoxy groups, the combination of bromoisobutyrate and dimethyl sulfoxide could act as a bromination reagent, delivering brominated pyrroloisoquinolines in acceptable to good yields (up to 82%).

The relationship among social capital, eHealth literacy and health behaviours in Chinese elderly people: a cross-sectional study.

BACKGROUND: Social capital has been linked to health behaviours, but the underlying mechanism is unclear. Previous studies have found that health literacy played the role of a mediator in the relationships among social capital, individual physical activity and nutrition. But it is not clear whether eHealth literacy mediates the impact of social capital on health behaviours. Therefore, our research aimed to explore the relationships among social capital (structural and cognitive social capital), eHealth literacy, and the health behaviours of elderly people, and to analyse the mediating effect of eHealth literacy, while providing a theoretical basis for a health behaviour intervention for elderly people. METHODS: From January to February 2019, we conducted a cross-sectional survey of 1201 Chinese people aged over 60 years using the Chinese Shortened Social Capital Scale (contains two subscales of structural social capital and cognitive social capital), eHealth Literacy Scale, and Health-Promoting Lifestyle Profile. We used structural equation modelling to test a hypothetical mediation model. RESULTS: The mean scores of social capital was 72.07 (SD = 13.03), 17.24 (SD = 9.34) for eHealth literacy, and 112.23 (SD = 23.25) for health behaviours. Social capital and eHealth literacy were significantly correlated with health behaviours, and social capital and structural social capital were significantly correlated with eHealth literacy. Lastly, eHealth literacy mediated the relationship between structural social capital and health behaviours. CONCLUSIONS: eHealth literacy was an important mediating factor for elderly people's structural social capital and health behaviours. Therefore, social capital and eHealth literacy must be considered when designing and implementing health behaviour intervention programmes for elderly people.

Type-I Core-Shell ZnSe/ZnS Quantum Dot-Based Resistive Switching for Implementing Algorithm.

Core-shell semiconductor quantum dots (QDs) are one of the biggest nanotechnology successes so far. In particular, type-I QDs with straddling band offset possess the ability to enhance the charge carriers capturing which is useful for memory application. Here, the type-I core-shell QD-based bipolar resistive switching (RS) memory with anomalous multiple SET and RESET processes was demonstrated. The synergy and competition between space charge limited current conduction (arising from charge trapping in potential well of type-I QDs) and electrochemical metallization (ECM, originating from redox reaction of Ag electrode) process were employed for modulating the RS behavior. Through utilizing stochastic RS mechanisms in QD-based devices, four situations of RS behaviors can be classified into three states in Markov chain for implementing the application of a true random number generator. Furthermore, a 6 × 6 cross-bar array was demonstrated to realize the generation of random letters with case distinction.

Characteristics of Chinese Families in Which Children and Both Parents Are Diagnosed with Malignant Tumors: A Retrospective Study.

Objective To characterize Chinese families in which both parents and at least one child are diagnosed with malignant diseases and provide reference for cancer screening or early detection in people whose both parents are diagnosed with cancer. Methods Medical records of all clients to the center of cancer screening and prevention of the National Cancer Center/Cancer Hospital between January 2008 and February 2018 were screened to select families in which both parents and at least one child were diagnosed with malignant diseases. The cancer profiles of fathers, mothers, sons and daughters, their age distribution at diagnosis, and similarity of cancers between two generations were analyzed. The proportions of each cancer in males and females of the cohort were compared with corresponding data from the National Cancer Center Registry of China (NCCRC) in 2013. Results Totally 135 families were identified from records of 33 200 clients. Proportion of lung cancer in fathers (40/135, 29.6%) and in mothers (38/135, 28.1%) were higher than the national data (23.9% in males and 14.9% in females, respectively). The proportion of breast cancer in daughters (35/109, 32.1%) was higher than that of mothers (14/135, 10.4%) and the national data (17.1%). In 71 father-son pairs of cancer, 46.5% (33/71) were of the same systematic disease, and 16.9% (12/71) were of the same cancer. These two indexes were 31.2% (n=34) and 10.1% (n=11), respectively in the 109 father-daughter pairs of cancer, 36.6% (n=26) and 8.5% (n=6) respectively in the 71 mother-son pairs of cancer, and 31.2% (n=34) and 20.2% (n=20) respectively in the 109 mother-daughter pairs of cancer. Sons were more likely to suffer from cancers originated from the same system as father's cancer than daughters (χ 2=4.299, P<0.05), and daughters were more likely to suffer from the same cancer as their mother's cancer than sons (χ 2=4.506, P<0.05). The age (mean ± standard deviation) of the daughters (52.4±12.7) and the sons (59.4±10.9) at diagnosis were significantly younger than the fathers (65.5±12.2) and the mothers (65.7 ±12.5) (all P<0.001). Conclusions For people whose both parents are diagnosed as cancer, screening or early detection examinations should cover a full range of cancers rather than the cancers their father and mother have suffered, or cancers stemmed from the same system as their parent's cancers. We suggest screening or early detection program for these special population start earlier than that for the general population, with emphasis on cancers derived from digestive system for males and women-specific cancers, i.e., breast cancer, ovarian cancer, cervical cancer and uterine cancer for females.

A Modified Technique Using Levator Aponeurosis-Müller Muscle-Reinforced Plication for Blepharoptosis Correction.

BACKGROUND: Blepharoptosis is a common and challenging clinical problem for oculoplastic surgeons, and various surgical techniques have been used to correct ptosis. The aims of this study were to present the clinical results of a modified technique using levator aponeurosis-Müller muscle-reinforced plication for blepharoptosis correction and to demonstrate its advantages over conventional advancement or plication methods. METHODS: This study was conducted in the Plastic Surgery Department of Sir Run Run Shaw Hospital between April 2017 and September 2018. By using this modified technique, the levator-Müller complex was reinforced with a plication suture that pierced under and through the levator-Müller complex, and the posterior and lower part of the levator-Müller complex was advanced to the tarsus, which provided permanent, reliable adhesion. The primary outcome was marginal reflex distance 1 preoperatively and postoperatively. Secondary outcomes were the cosmetic outcome, complications, and operative time. RESULTS: Eighty-six patients (169 eyelids) underwent this modified surgery. Patients' average age was 26 ± 7.6 years, and the median follow-up was 14 months. The preoperative and postoperative mean marginal reflex distance 1 values were 1.72 ± 0.32 and 3.69 ± 0.28 mm, respectively. The amount of plication ranged from 4 to 15 mm. The overall surgical success rate was 88.17%. Some complications were observed including undercorrection (5.92%), asymmetry (4.73%), lagophthalmos (0.59%), and conjunctival prolapse (0.59%). CONCLUSIONS: The modified technique provided good functional and cosmetic outcomes for blepharoptosis correction by avoiding unpredicted adhesion, and it has its advantages including simplicity, easy adjustment of the eyelid height intraoperatively, minimal edema formation, and high success rate.

Fabrication of paper-based SERS substrates by spraying silver and gold nanoparticles for SERS determination of malachite green, methylene blue, and crystal violet in fish.

A disposable surface-enhanced Raman scattering (SERS) substrate was prepared by successively spraying silver nanoparticles (AgNPs) and gold nanoparticles (AuNPs) onto commercial filter paper using an inexpensive consumer sprayer. The strong surface enhancement of AgNPs and chemical stability of AuNPs can be advantageously combined. The substrate exhibited excellent SERS activity for malachite green (MG), methylene blue (MB), and crystal violet (CV) under 785-nm excitation, with limits of detection (LODs) of 4.3 × 10-9, 2.0 × 10-8, and 8.1 × 10-8 M, respectively. The substrate exhibited long-term stability, and it can be stored under ambient conditions for 4 weeks with a relative standard deviation of less than 3% among peak intensities. The substrate also showed good reproducibility with a relative standard deviation of 7.1% among different substrate peak intensities. The substrates enable on-site determination of residual fishery drugs and distinguish MG, MB, and CV mixtures in spiked fish within 5 min, and the average recoveries in fish scales and fish meat were better 90.1% and 76.9%, respectively. The method exhibited rapidity, simplicity, and high sensitivity and is expected to be used for the screening of additives in food.

Ameliorative effects of the traditional Chinese medicine formula Qing-Mai-Yin on arteriosclerosis obliterans in a rabbit model.

CONTEXT: Qing-Mai-Yin (QMY) is a clinically used herbal formula for treating arteriosclerosis obliterans (ASO). OBJECTIVE: To evaluate the chemical constituents and effects of QMY on ASO rabbit model. MATERIALS AND METHODS: Forty-eight New Zealand rabbits were divided into six groups (n = 8): normal (normal rabbits treated with 0.5% CMC-Na), vehicle (ASO rabbits treated with 0.5% CMC-Na), positive (simvastatin, 1.53 mg/kg), and QMY treatment (300, 600, and 1200 mg/kg). ASO rabbit model was prepared by high fatty feeding, roundly shortening artery, and bovine serum albumin immune injury. QMY (300, 600 and 1200 mg/kg) was orally administered for 8 weeks. The effects and possible mechanisms of QMY on ASO rabbits were evaluated by pathological examination, biochemical assays, and immunohistochemical assays. The compositions of QMY were analysed using HPLC-Q-TOF-MS/MS analysis. RESULTS: Compared to the vehicle rabbit, QMY treatment suppressed plaque formation and intima thickness in aorta, and decreased intima thickness, whereas increased lumen area of femoral artery. Additionally, QMY treatment decreased TC, TG and LDL, decreased CRP and ET, and increased NO and 6-K-PGF1α in serum. Furthermore, the potential mechanisms studied revealed that QMY treatment could suppress expression of TNF-α, IL-6, ICAM-1 and NF-κB in endothelial tissues, and increase IκB. In addition, HPLC analysis showed QMY had abundant anthraquinones, stilbenes, and flavonoids. CONCLUSION: QMY has ameliorative effects on ASO rabbit, and the potential mechanisms are correlated to reducing inflammation and down-regulating NF-κB. Our study provides a scientific basis for the future application and investigation of QMY.

Mechanistic Insights into the Chemo- and Regio-Selective B(C6F5)3 Catalyzed C-H Functionalization of Phenols with Diazoesters.

The Lewis acidic B(C6F5)3 was recently demonstrated to be effective for the C-H alkylation of phenols with diazoesters. The method avoids the general hydroxyl activation in transition-metal catalysis. Ortho-selective C-H alkylation occurs regardless of potential para-selective C-H alkylation and O-H alkylation. In the present study, a theoretical calculation was carried out to elucidate the reaction mechanism and the origin of chemo- and regio-selectivity. It is found that the previously proposed B(C6F5)3/N or B(C6F5)3/C bonding-involved mechanisms are not favorable, and a more favored one involves the B(C6F5)3/C═O bonding, rate-determining N2 elimination, selectivity-determining electrophilic attack, and proton transfer steps. Meanwhile, the new mechanism is consistent with KIE and competition experiments. The facility of the mechanism is attributed to two factors. First, the B(C6F5)3/C═O bonding reduces the steric hindrance during electrophilic attack. Second, the bonding forms the conjugated system by which the LUMO energy is reduced via the electron-withdrawing B(C6F5)3. The ortho-selectivity resulted from the greater ortho-C-C (than para-C-C) interaction and the O-H···O and O-H···F hydrogen-bond interaction during electrophilic attack. The greater C-C (than C-O) interaction and the π-π stacking between the benzene rings of phenol and diazoester concerted contribute to the chemo-selective C-H alkylation.