Organocatalytic Enantioselective Synthesis of Axially Chiral N,N'-Bisindoles.

This study establishes the first organocatalytic enantioselective synthesis of axially chiral N,N'-bisindoles via chiral phosphoric acid-catalyzed formal (3+2) cycloadditions of indole-based enaminones as novel platform molecules with 2,3-diketoesters, where de novo indole-ring formation is involved. Using this new strategy, various axially chiral N,N'-bisindoles were synthesized in good yields and with excellent enantioselectivities (up to 87 % yield and 96 % ee). More importantly, this class of axially chiral N,N'-bisindoles exhibited some degree of cytotoxicity toward cancer cells and was derived into axially chiral phosphine ligands with high catalytic activity. This study provides a new strategy for enantioselective synthesis of axially chiral N,N'-bisindoles using asymmetric organocatalysis and is the first to realize the applications of such scaffolds in medicinal chemistry and asymmetric catalysis.

Correlation analysis of self-directed learning ability, self-efficacy and academic burnout of junior nursing college students in closed management colleges.

AIMS: To understand the status quo of self-directed learning ability, self-efficacy and academic burnout of junior nursing college students, since the closed management mode was implemented during COVID-19 pandemic disease. DESIGN: Cross-sectional study. METHODS: Participants came from 3,051 junior nursing college students of a college in Zhengzhou City, Henan Province, China. Data were collected by online questionnaire and analysed by SPSS25.0 (a statistical package for social science) and AMOS24.0 software. RESULTS: High self-directed learning ability and self-efficacy were related to low levels of academic burnout (p < .01). In addition, the analysis of mediation effect indicated that the influence of self-directed learning ability on academic burnout was not mediated by self-efficacy.

[Visual analysis of research hotspots and frontiers on randomized controlled trials of acupuncture and moxibustion in the past 10 years].

Retrieved the literature on randomized controlled trials (RCT) of acupuncture and moxibustion from 2011 to 2020 in the Web of Science (WOS) database, and explored research hotspots and frontiers in the field of acupuncture and moxibustion by visually analyze to countries, institutions, authors, keywords, cited literature, etc. using CiteSpace V5.6.R2. A total of 1147 articles were included. China has the largest number of publications, and the top 3 publications are Beijing University of Chinese Medicine, Capital Medical University and Kyung Hee University. The hot research interventions in acupuncture and moxibustion include acupuncture, electroacupuncture, and bee acupuncture. The hot research topics include nerve regeneration, spasms, nausea, pain, obesity, cancer, etc. The research frontiers include acupuncture analgesia, diversification of acupuncture and its clinical effects, brain effects of acupuncture and acupuncture clinical mechanisms. It is believed that the cooperation between countries and institutions should be strengthened in the future, and deeper research should be carried out on the research content that is both hot spot and frontier.

Organocatalytic Atroposelective Synthesis of N-N Axially Chiral Indoles and Pyrroles by De Novo Ring Formation.

The first highly atroposelective construction of N-N axially chiral indole scaffolds was established via a new strategy of de novo ring formation. This strategy makes use of the organocatalytic asymmetric Paal-Knorr reaction of well-designed N-aminoindoles with 1,4-diketones, thus affording N-pyrrolylindoles in high yields and with excellent atroposelectivities (up to 98 % yield, 96 % ee). In addition, this strategy is applicable for the atroposelective synthesis of N-N axially chiral bispyrroles (up to 98 % yield, 97 % ee). More importantly, such N-N axially chiral heterocycles can be converted into chiral organocatalysts with applications in asymmetric catalysis, and some molecules display potent anticancer activity. This work not only provides a new strategy for the atroposelective synthesis of N-N axially chiral molecules but also offers new members of the N-N atropisomer family with promising applications in synthetic and medicinal chemistry.

Rational Design of Axially Chiral Styrene-Based Organocatalysts and Their Application in Catalytic Asymmetric (2+4) Cyclizations.

A new class of axially chiral styrene-based thiourea tertiary amine catalysts, which have unique characteristics such as an efficient synthetic route, multiple chiral elements, and multiple activating groups, has been rationally designed. These new chiral catalysts have proven to be efficient organocatalysts, enabling the chemo-, diastereo-, and enantioselective (2+4) cyclization of 2-benzothiazolimines with homophthalic anhydrides in good yields (up to 96 %) with excellent stereoselectivities (all >95:5 dr, up to 98 % ee). More importantly, theoretical calculations elucidated the important role of an axially chiral styrene moiety in controlling both the reactivity and enantioselectivity. This work not only represents the first design of styrene-based chiral thiourea tertiary amine catalysts and the first catalytic asymmetric (2+4) cyclization of 2-benzothiazolimines, but also gives an in-depth understanding of axially chiral styrene-based organocatalysts.

Epigallocatechin gallate regulates inflammatory responses and new bone formation through Wnt/ß-Catenin/COX-2 pathway in spondyloarthritis.

OBJECTIVE: Spondyloarthritis (SpA) is mainly characterized by bone erosion, new bone formation, inflammation and potential disability. Epigallocatechin gallate (EGCG) has been proved to be closely related with the regulation of inflammation and bone metabolism. However, whether EGCG could improve SpA remains unclear. METHODS: SpA animal model was established using proteoglycan. Cell proliferation were measured by CCK-8 assay. The mRNA expression levels of genes were detected using qRT-PCR, protein levels were assessed via western blotting and immunohistochemistry. ELISA assay was performed to examined the inflammatory cytokine release. Lesions in spine cartilage tissues were observed using hematoxylin-eosin (HE) and Safranin O staining. Alkaline phosphatase (ALP) assay and Alizarin Red S staining was used to investigate osteoblast mineralization. RESULTS: We found that EGCG could inhibit inflammation and new bone formation in SpA mice. Besides, inflammatory factor expression and osteogenic differentiation in osteoblasts isolated from SpA mice were also decreased by EGCG. Further, EGCG treatment suppressed the activation of Wnt/ß-Catenin/COX-2 pathway and the activator of this pathway partially reversed the effects of EGCG on inflammation and osteoblast differentiation. CONCLUSIONS: EGCG repressed inflammatory responses and new bone formation, and further improved SpA through Wnt/ß-Catenin/COX-2 pathway. Our findings may provide a new thought for the prevention and treatment of SpA.

[Research status and prospects on adenosine receptor mechanism of acupuncture for myocardial ischemia].

The relationship between adenosine receptor (AdoR) and myocardial ischemia (MI), effect of acupuncture for MI and action mechanism of acupuncture improving MI by regulating AdoR are summarized. The existing researches have preliminarily reflected that the improvement of MI treated with acupuncture may be achieved by influencing the expression of AdoR. However, there are still some limitations, e.g. most of the research regimens are single-acupoint, the research results are not entirely consistent and the interaction of AdoRs are ignored, all these need to be further verified and supplemented.

Effect and Safety of CX-DZ-II Intelligent Electroacupuncture Therapeutic Instrument for Neck Pain Caused by Cervical Spondylos: Study Protocol for A Randomized Controlled Trial.

BACKGROUND: Neck pain caused by cervical spondylosis (CS) is a chronic pain condition, with an increasingly high incidence in the general population. Electroacupuncture is a common analgesic modality that has been widely applied in neck pain treatment. However, current electroacupuncture instruments used in the clinic have low intelligence levels and obscure parameter standards. We here designed this study for assessing the effect and safety of a new, intelligent electroacupuncture instrument, the CX-DZ-II, in treating neck pain. METHODS: The present study is a prospective, two-center, randomized, controlled, open-label, non-inferiority trial for CX-DZ-II on treating neck pain caused by CS. Totally 160 eligible patients will be included in this trial and randomly assigned to an experimental group and a control group in a 1:1 ratio. A semi-standard acupoint selection strategy will be employed. In the experimental group, selected acupoints will be stimulated by CX-DZ-II. Electroacupuncture treatment will be accomplished by a pre-existing electroacupuncture instrument in the control group. The duration of treatment will be 2 weeks. The primary outcome is the change of Visual Analog Scale (VAS) score after one course of treatment. The secondary outcomes include the VAS scores after each treatment, the responder rate, drug-usage rate of non-steroidal antipyretic analgesics, the rate of adverse events occurrence, and the performance of instrument. DISCUSSION: This study will evaluate the effect and safety of the CX-DZ-II intelligent electroacupuncture therapeutic instrument in comparison with a pre-existing non-intelligent instrument in the treatment of neck pain caused by CS. The results will hopefully demonstrate a more optimal electroacupuncture instrument for the treatment of neck pain. (Trial registration No. gov NCT03005301).

[Mechanism of acupoint selection along meridians to improve adenosine receptor of myocardial ischemia based on acupoint specificity].

OBJECTIVE: To explore the action mechanism of acupoint selection along meridians to improve adenosine receptor in myocardial ischemia (MI) rats by comparing the effects of acupoint selection along meridians, acupoint selection at other meridians and non-acupoint on expression of adenosine receptor. METHODS: A total of 120 SD rats were randomly divided into a blank group, a sham operation group, a model group, an acupoint-selection-along-meridians (ASAM) group, an acupoint-selection-at-other-meridians (ASAOM) group and a non-acupoint group, 20 rats in each group. The model of MI was not made in the blank group; the left anterior descending coronary artery was not ligated after thoracotomy in the sham operation group; the model of MI was made but acupuncture was not given in the model group. After the model of MI was made, electroacupuncture (EA) was applied at "Neiguan" (PC 6) in the ASAM group, at "Hegu" (LI 4) in the ASAOM group, and at the area between the third and fourth metatarsal bone in the non-acupoint group. EA was given 20 min per treatment, once a day for 5 days. After treatment, the TTC staining was used to detect myocardial infarction, the Tunel method was used to detect cardiomyocyte apoptosis, and the immunohistochemistry was used to detect the expression of adenosine receptors A1, A2a and A2b. RESULTS: Compared with the blank group and the sham operation group, the percentage of myocardial infarction and apoptotic rate of myocardial cells in the model group were increased significantly (P<0.01). After EA treatment, compared with the model group, the percentage of myocardial infarction and apoptotic rate of myocardial cells in the ASAM group were decreased significantly (P<0.01), and the expression levels of adenosine receptors A1, A2a and A2b were increased significantly (P<0.01). The percentage of myocardial infarction and apoptotic rate of myocardial cells in the ASAM group were significantly lower than those in the ASAOM group and the non-acupoint group (P<0.01), and the expression levels of adenosine receptors A1, A2a and A2b in the ASAM group were significantly higher than those in the ASAOM group and non-acupoint group (P<0.01). CONCLUSION: Compared with acupoint selection at other meridians or non-acupoints, acupoint selection along meridians can effectively regulate the expression of adenosine receptors A1, A2a and A2b, improve the condition of myocardial infarction, inhibit myocardial cell apoptosis, and consequently protect ischemic myocardium.