Chirality is not only a natural phenomenon but also a bridge between chemistry and life sciences.An effective way to obtain a single enantiomer is through racemates resolution.Recent literature shows that chiral metal-organic frameworks(CMOFs)have many applications in various fields because of their diverse topologies and functionalities.This review outlines the design idea and summarizes the latest synthesis strategies and applications of CMOFs.It highlights key advances and issues in the separation domain.In conclusion,the review provides perspectives on the challenges and prospective advance-ments of CMOFs materials and CMOFs-based separation technologies.

Objective To investigate the effect and mechanism of nodakenin(Nod)in neuropathic pain(NP).Methods Differential expression genes in the primary somatsensory cortex(S1)of NP data and overlapping genes between the dataset and mitochondrial data were screened and analyzed.Overlapping gene interaction networks were overlapped and core genes were screened.A total of 27 mice were randomly divided into the sham operation group,the model group and the drug administration group(9 mice/group).The chronic compression injury model of sciatic nerve was constructed in the model group and the drug administration group.Nod 10 mg/kg was intraperitoneally injected into the drug administration group for 1 week.Changes of pain behavior and motor ability in mice were detected.HE staining and Nissl staining were used to detect effects of nerve injury and inflammation on brain tissue of S1 region of mice.The expression levels of interleukin-1β,early gene(c-Fos),panthenol-cytochrome c reductase complex III subunit(Uqcrq)and ubiquinone oxidoreductase subunit(Nduf)b5 in S1 brain region were analyzed by Western blot assay.Molecular docking was used to study the target of Nod.PC12 cells were divided into the control group,the IL-1β group(1 μmol/L IL-1β treatment)and the IL-1β+Nod group(1 μmol/L IL-1β+1 μmol/L Nod treatment),and mitochondrial membrane potential was detected in each group.Results In the NP dataset GSE180627,S1 brain region contained 293 differentially expressed genes,and the mitochondrial data contained 1 082 genes.There were 34 overlapping genes,and genes related to oxidative phosphorylation and electron transport chain were enriched.The protein interaction network showed that core genes included electron transport chain related proteins Ndufb5,Uqcrq,Ndufs8,Ndufa7,Ndufa3,Cox6b1 and Mrps33.Compared with the model group,the mechanical foot shrinkage threshold,thermal foot shrinkage reflex latency and rod rotation residence time of mice were increased in the drug administration group,the number of inflammatory infiltrating cells in S1 tissue and the number of Nislet bodies in neurons,expression levels of c-Fos and IL-1β in neurons were decreased,and expression levels of Uqcrq and Ndufb5 were increased(P＜0.05).Molecular docking showed that Nod could bind Uqcrq and Ndufb5.Compared with the IL-1β group,the fluorescence signal of mitochondrial membrane potential was enhanced in the IL-1β+Nod group(P＜0.05).Conclusion Nodakenin can improve pain behavior in mice,and its mechanism involves ameliorating mitochondrial damage in S1.

Objective: To investigate the mechanism of in alleviating colonic mucosal inflammation in ten-eleven translocation (TET) protein 2 gene knockout (TET2-/-) mice with ulcerative colitis (UC) by regulating DNA methyltransferase (DNMT) and DNA hydroxymethylase. Methods: Male specific pathogen-free (SPF) grade C57BL/6J wild-type (WT) mice (n = 8) and TET2-/- mice (n = 20) were used to establish UC models by freely drinking 3% dextran sulfate sodium solution for 7 d. After UC model validation through histopathological examination in two mice from each type, the remaining mice were divided into four groups (n = 6 in each group): WT model (WT + UC), TET2-/- model (TET2-/- + UC), TET2-/- mild moxibustion (TET2-/- + MM), and TET2-/- electroacupuncture (TET2-/- + EA) groups. TET2-/- + MM group received mild moxibustion on Tianshu (ST25) and Qihai (CV6) for 10 min daily for 7 d. The TET2-/- + EA group also applied electroacupuncture (1 mA, 2/100 Hz) at the same acupoints for 10 min daily for 7 d. The disease activity index (DAI) scores of each group of mice were accessed daily. The colon lengths of mice in groups were measured following intervention. The pathological changes in the colon tissues were observed with hematoxylin and eosin (HE) staining. The concentrations of interleukin (IL)-6, C-C motif chemokine 17 (CCL17), and C-X-C motif chemokine ligand 10 (CXCL10) in serum were detected by enzyme-linked immunosorbent assay (ELISA). The expression of DNMT proteins (DNMT1, DNMT3A, and DNMT3B) in the colon tissues was detected by immunohistochemistry. The expression of 5-methylcytosine (5-mC), 5-hydroxymethylcytosine (5-hmC), histone deacetylase 2 (HDAC2), and DNA hydroxymethylase family proteins (TET 1 and TET3) was detected using immunofluorescence, which also determined the co-localization of TET1 and IL-6 protein. Results: Compared with WT + UC group, TET2-/- + UC group exhibited significantly higher DAI scores and shorter colon lengths (P < 0.01). Both mild moxibustion and electroacupuncture significantly decreased DAI scores and ameliorated colon shortening in TET2-/- mice (P < 0.001). Histopathological scores of TET2-/- + UC mice were significantly higher than those of WT + UC group (P < 0.001) and were significantly reduced after both mild moxibustion and electroacupuncture interventions (P < 0.001). Serum levels of IL-6, CCL17, and CXCL10 were significantly elevated in TET2-/- + UC group compared with WT + UC group (P < 0.001). Mild moxibustion significantly reduced IL-6, CCL17, and CXCL10 levels (P < 0.001, P < 0.001, and P < 0.01, respectively), while electroacupuncture also significantly reduced IL-6, CCL17, and CXCL10 levels (P < 0.05, P < 0.01, and P < 0.01, respectively). TET2-/- + UC mice showed increased expression levels of DNMT1, DNMT3A , DNMT3B, and 5-mC (P < 0.05, P < 0.01 and P < 0.001, respectively), with decreased expression levels of TET1, TET3, 5-hmC, and HDAC2 (P < 0.001). Mild moxibustion significantly reduced DNMT1, DNMT3B, and 5-mC levels (P < 0.05, P < 0.01, and P < 0.001, respectively), while increasing expression levels of TET1, TET3, 5-hmC, and HDAC2 (P < 0.001, P < 0.001, P < 0.05, and P < 0.001, respectively). Electroacupuncture significantly decreased 5-mC and DNMT3B levels (P < 0.001 and P < 0.01, respectively) and increased 5-hmC and HDAC2 levels (P < 0.05 and P < 0.001, respectively), but did not significantly affect TET1 and TET3 expression (P > 0.05). Compared with TET2-/- + MM group, TET2-/- + EA group showed significantly higher 5-mC expression (P < 0.001). TET2-/- + UC group exhibited markedly increased IL-6 expression and higher co-localization of TET1 and IL-6 in mucosal epithelium, whereas minimal IL-6 expression was observed in the other groups. Conclusion Mild moxibustion and electroacupuncture significantly ameliorate colonic inflammation exacerbated by TET2 deficiency in UC mice via epigenetic modulation. Distinct mechanisms exist between the two interventions: mild moxibustion regulates both DNMT and hydroxymethylase, whereas electroacupuncture primarily affects DNMT.

Chirality is not only a natural phenomenon but also a bridge between chemistry and life sciences. An effective way to obtain a single enantiomer is through racemates resolution. Recent literature shows that chiral metal-organic frameworks (CMOFs) have many applications in various fields because of their diverse topologies and functionalities. This review outlines the design idea and summarizes the latest synthesis strategies and applications of CMOFs. It highlights key advances and issues in the separation domain. In conclusion, the review provides perspectives on the challenges and prospective advancements of CMOFs materials and CMOFs-based separation technologies.

Allergen-associated proteases, pollutants, viral and fungal pathogens disrupted epithelial barrier integrity and promoted airway epithelial release of alarmins.Epithelial-derived Alarmins include thymic stromal lymphopoietin (TSLP), interleukin 33 (IL-33), and interleukin 25 (IL-25), which acted on a variety of effector cells such as dendritic cells (DCs), T-lymphocytes, innate lymphocyte cells (ILC2), B-lymphocytes, eosinophils, mast cells, basophils, and macrophages. T-lymphocytes, innate lymphocyte cell type 2 (ILC2), B-lymphocytes, eosinophils, mast cells, basophils and macrophages are the effector cells. By affecting the physiological and biochemical functions of target cells, such as proliferation and differentiation, survival and recruitment, and material metabolism, the alarmins had activated the intrinsic and adaptive immunity, and played a key role in allergic diseases such as bronchial asthma, atopic dermatitis, allergic rhinitis, and urticaria. A variety of monoclonal antibodies targeting epithelial-derived alarm factors have been developed for the above allergic diseases, and some of these products are already put into clinical use. As epidemiological studies showed that skin allergy closely related to airway allergy, allergic co-morbidities has imposed a heavy economic and psychological burden to patients. In-depth understanding the mechanism of alarmins will help to understand the developing and progression of allergic diseases, and develop more effective diagnostic and therapeutic strategies for allergic co-morbidities. This article reviews the mechanism and recent research advances of epithelial-derived alarmins in a variety of allergic diseases.

Allergen-associated proteases, pollutants, viral and fungal pathogens disrupted epithelial barrier integrity and promoted airway epithelial release of alarmins.Epithelial-derived Alarmins include thymic stromal lymphopoietin (TSLP), interleukin 33 (IL-33), and interleukin 25 (IL-25), which acted on a variety of effector cells such as dendritic cells (DCs), T-lymphocytes, innate lymphocyte cells (ILC2), B-lymphocytes, eosinophils, mast cells, basophils, and macrophages. T-lymphocytes, innate lymphocyte cell type 2 (ILC2), B-lymphocytes, eosinophils, mast cells, basophils and macrophages are the effector cells. By affecting the physiological and biochemical functions of target cells, such as proliferation and differentiation, survival and recruitment, and material metabolism, the alarmins had activated the intrinsic and adaptive immunity, and played a key role in allergic diseases such as bronchial asthma, atopic dermatitis, allergic rhinitis, and urticaria. A variety of monoclonal antibodies targeting epithelial-derived alarm factors have been developed for the above allergic diseases, and some of these products are already put into clinical use. As epidemiological studies showed that skin allergy closely related to airway allergy, allergic co-morbidities has imposed a heavy economic and psychological burden to patients. In-depth understanding the mechanism of alarmins will help to understand the developing and progression of allergic diseases, and develop more effective diagnostic and therapeutic strategies for allergic co-morbidities. This article reviews the mechanism and recent research advances of epithelial-derived alarmins in a variety of allergic diseases.

Objective To investigate the effect and mechanism of nodakenin(Nod)in neuropathic pain(NP).Methods Differential expression genes in the primary somatsensory cortex(S1)of NP data and overlapping genes between the dataset and mitochondrial data were screened and analyzed.Overlapping gene interaction networks were overlapped and core genes were screened.A total of 27 mice were randomly divided into the sham operation group,the model group and the drug administration group(9 mice/group).The chronic compression injury model of sciatic nerve was constructed in the model group and the drug administration group.Nod 10 mg/kg was intraperitoneally injected into the drug administration group for 1 week.Changes of pain behavior and motor ability in mice were detected.HE staining and Nissl staining were used to detect effects of nerve injury and inflammation on brain tissue of S1 region of mice.The expression levels of interleukin-1β,early gene(c-Fos),panthenol-cytochrome c reductase complex III subunit(Uqcrq)and ubiquinone oxidoreductase subunit(Nduf)b5 in S1 brain region were analyzed by Western blot assay.Molecular docking was used to study the target of Nod.PC12 cells were divided into the control group,the IL-1β group(1 μmol/L IL-1β treatment)and the IL-1β+Nod group(1 μmol/L IL-1β+1 μmol/L Nod treatment),and mitochondrial membrane potential was detected in each group.Results In the NP dataset GSE180627,S1 brain region contained 293 differentially expressed genes,and the mitochondrial data contained 1 082 genes.There were 34 overlapping genes,and genes related to oxidative phosphorylation and electron transport chain were enriched.The protein interaction network showed that core genes included electron transport chain related proteins Ndufb5,Uqcrq,Ndufs8,Ndufa7,Ndufa3,Cox6b1 and Mrps33.Compared with the model group,the mechanical foot shrinkage threshold,thermal foot shrinkage reflex latency and rod rotation residence time of mice were increased in the drug administration group,the number of inflammatory infiltrating cells in S1 tissue and the number of Nislet bodies in neurons,expression levels of c-Fos and IL-1β in neurons were decreased,and expression levels of Uqcrq and Ndufb5 were increased(P＜0.05).Molecular docking showed that Nod could bind Uqcrq and Ndufb5.Compared with the IL-1β group,the fluorescence signal of mitochondrial membrane potential was enhanced in the IL-1β+Nod group(P＜0.05).Conclusion Nodakenin can improve pain behavior in mice,and its mechanism involves ameliorating mitochondrial damage in S1.

Autoimmune diseases of the nervous system are a group of diseases caused by the body′s immune system attacking its own nervous system, resulting in structural damage and functional impairment of the corresponding tissues. Interventional clearance of pathogenic auto-antibodies has been shown to be effective in reducing immune damage, inhibiting disease progression and improving prognosis through extensive basic research and long-term clinical practice. The neonatal Fc receptor (FcRn)-mediated circulating protection mechanism of IgG contributes to the long half-life and high plasma levels of IgG. FcRn inhibitors are able to target and block the binding of FcRn to IgG, accelerating IgG clearance and reducing IgG levels. Therefore, the use of FcRn inhibitors in the treatment of autoimmune diseases of the nervous system could theoretically help to accelerate the clearance of pathogenic IgG, achieve good clinical efficacy and have promising applications. Research in this area has made considerable progress in recent years and this article will review this.

OBJECTIVE: To assess the value of copy number variation sequencing (CNV-seq) for revealing the genetic etiology of fetuses with isolated ventricular septal defect (VSD). METHODS: From December 2017 to December 2020, 69 fetuses with isolated VSD were identified at the First Affiliated Hospital of Zhengzhou University. Meanwhile, 839 similar prenatal cases were selected from public databases including Wanfang data, Wanfang Medicine, and China National Knowledge Infrastructure (CNKI) by using keywords such as "Ventricular septal defect", "Copy number variation", and "Prenatal". A total of 908 fetuses with isolated VSD were analyzed. CNV-seq was carried out for 69 fetuses. RESULTS: Among the 908 fetuses, 33 (3.63%) were found to harbor pathogenic CNVs, which included 11 chromosomal aneuploidies (1.21%) and 22 pathogenic CNVs (2.42%). The pathogenic CNVs have involved 12 genetic syndromes, with those known to involve the heart development including 5 cases of 22q11.21 deletion syndrome, 2 cases of 4q terminal deletion syndrome, and 1 case of 9q subtelomere deletion syndrome. The outcome of pregnancies for 15 fetuses with pathogenic CNVs was known, of which 12 were terminated, and 3 had spontaneous closure of the ventricular septum after birth, but 1 of them had other abnormalities. CONCLUSION Fetuses with isolated VSD have a relatively high risk for chromosomal abnormalities, for which CNV-seq should be recommended.
Female ; Pregnancy ; Humans ; DNA Copy Number Variations ; Heart Septal Defects, Ventricular/genetics* ; 22q11 Deletion Syndrome ; Fetus

OBJECTIVE To study the regulator y mech anism of glaucocalyxin A （GLA） on autophagy and apoptosis of HCCLM3 hepatocellular carcinoma cells. METHODS HCCLM3 cells were taken ，and control group ，GLA 2.5 μg/mL group，GLA 5 μg/mL group and GLA 10 μg/mL group were mainly set according to different experimental purposes. In control group，only complete medium was added ；in each administration group ，complete medium containing the corresponding final concentration of GLA was added. Cell cycle distribution and apoptosis were detected by flow cytometry ；mitochondrial morphology and autophagy were observed by transmission electron microscope （only control group ，GLA 5 μg/mL group）；JC-1 staining and fluorescence inverted microscope were used to observe and detect the mitochondrial membrane potential of the cells ；Western blot assay was used to detect the protein expression of Bcl- 2， Bax， Beclin1 and cleaved caspase- 3 proteins in the cells ； the co-immunoprecipitation method was used to detect the binding and dissociation of Bcl- 2 and Beclin 1（only GLA 5 μg/mL group， GLA 10 μg/mL group）. RESULTS Compared with control group ，GLA 5 μg/mL and GLA 10 μg/mL could induce a significant arrest of the cell cycle in the G 2-M phase for HCCLM 3，a significant decrease in mitochondrial membrane potential ，an increase in apoptosis as well as significant promotion of the protein expression of Bax ，cleaved caspase- 3 and Beclin 1，and significant inhibition of the protein expression of Bcl- 2（P＜0.01）. GLA 5 μg/mL also significantly changed mitochondrial morphology and increased autophagosomes. The results of co-immunoprecipitation showed that compared with GLA 5 μg/mL，GLA 10 μg/mL could enhance the binding of Bcl- 2 and Beclin 1. CONCLUSIONS GLA can regulate the autophagy and apoptosis of HCCLM 3 cells by Bcl-2/Beclin1 target. The effect is closely related to the dose of GLA.