Bifunctional Supertetrahedral Chalcogenolate Cluster-Based Assembly Materials Constructed by a Photoactive Ligand.

The assembly of supertetrahedral chalcogenolate clusters (SCCs) and multifunctional organic linkers could lead to the formation of tunable structures and synergistic properties. Two SCC-based assembled materials (SCCAM-1 and -2) constructed by a triangular chromophore ligand, tris(4-pyridylphenyl)amine, were successfully synthesized and characterized. The SCCAMs demonstrate unusually long-lived afterglow at low temperatures (83 K) and efficient activities for the photocatalytic degradation of organic dye in water.

Analysis of Pediatric Surgical Disease Spectrum in a Tertiary Hospital.

Objective: To analyze the main disease composition of children hospitalized in pediatric surgery, explore the correlation between disease types and gender, and provide a reference for hospital management and pediatric disease prevention. Methods: Using ICD-10 codes as the classification standard for disease diagnosis, a statistical analysis was conducted on the disease composition of children hospitalized in the Pediatric Surgery Department of the Second Affiliated Hospital of Xi'an Jiaotong University from January 1, 2015, to December 31, 2015, followed by the establishment of a clinical database. A total of 1647 male patients and 817 female patients were enrolled in the study, resulting in a male-to-female ratio of 2:1. The age range of the patients spanned from 0 to 18 years, with a marked imbalance in patient distribution among the various age groups. Statistical analysis was conducted using SPSS version 18.0 software. A chi-square test was performed to analyze the differences in the composition of disease systems and the composition of major diseases in terms of sex and age. Results: Pediatric patients were admitted with complex and diverse diseases in 2015, involving 15 systems of the human body and 400 diseases. Digestive system diseases, tumors, congenital malformations, and genitourinary system diseases were the top four diseases accounting for 83.5% of all pediatric cases. 561 patients were aged 0 years, accounting for 22.3% of all cases, while 1,801 patients fell within the 0-5 years age group, constituting 73.1% of the total. The differences in disease system composition among different sex and age groups of pediatric surgical inpatients were statistically significant (P = .001). There are statistically significant differences in the length of hospital stay and hospitalization costs among pediatric surgical inpatients in different age groups (P = .001). Conclusion: To strengthen the diagnosis and treatment of pediatric surgical diseases, we should strengthen the construction of key departments, optimize the consultation process according to the characteristics of children's disease spectrum, and improve the level of diagnosis and treatment of pediatric surgical diseases.

Study on the relationship between SLCO1B1 and ApoE gene polymorphisms and the risk of coronary heart disease in the Mongolian population.

Objective This study aimed to analyze the influence of SLCO1B1 and APOE gene polymorphisms on coronary heart disease in Mongolian population who living in Ordos area. Methods From January 2019 to June 2020, 200 Mongolian patients with coronary heart disease admitted to our hospital and other banner hospitals were selected as the case group. At the same time, 150 randomly selected healthy Mongolian people from medical examination centers comprised the control group. The polymorphisms of SLCO1B1 (388A>G, 521 T > C) and ApoE (388 T > C, 526 C > t) were detected by real-time polymerase chain reaction. Combined with environmental data, the effect of gene polymorphism on coronary heart disease was explored. Results Both SLCO1B1 and ApoE polymorphisms satisfied Hardy-Weinberg equilibrium. The SLCO1B1 genotype *1a/*1b showed the highest frequency in the case group, accounting for 35.0%, while The SLCO1B1 genotype *1b/*1b showed the highest frequency in the control group, accounting for 32.0%. Allele *1b was the most commonly seen allele in both the case group and control group (57.8% and 53.7%, respectively). Meanwhile, The difference in the distribution of SLCO1B1 *1a/*15 genotype between the two groups was statistically significant (P < .05). Conclusion The results showed that the SLCO1B *1a/*15 genotype, ApoE ε3 /ε3 genotype, and ε3 allele reduced the risk of coronary disease in the Mongolian population, making them protective genes against this disease, while the ApoE ε4 allele increased the risk of coronary disease, making it a coronary disease risk factor.

Upregulation of miR-219a-5p Decreases Cerebral Ischemia/Reperfusion Injury In Vitro by Targeting Pde4d.

BACKGROUND: Ischemic stroke is the leading cause of disability and death globally. Micro-RNAs (miRNAs) have been reported to play important roles in the development and pathogenesis of the nervous system. However, the exact function and mechanism of miRNAs have not been fully elucidated about brain damage caused by cerebral ischemia/reperfusion (I/R). METHODS: In this study, we explored the neuroprotective effects of miR-219a-5p on brain using an in vitro ischemia model (mouse neuroblastoma N2a cells treated with oxyglucose deprivation and reperfusion), and in vivo cerebral I/R model in mice. Western blot assay and Reverse Transcription-Polymerase Chain Reaction were used to check the expression of molecules involved. Flow cytometry and cholecystokinin were used to examine cell apoptosis, respectively. RESULTS: Our research shows that miR-219a-5p gradually decreases in cerebral I/R models in vivo and in vitro. In vitro I/R, we find that miR-219a-5p mimics provided evidently protection for cerebral I/R damage, as shown by increased cell viability and decreased the release of LDH and cell apoptosis. Mechanically, our findings indicate that miR-219a-5p binds to cAMP specific 3', 5'-cyclic phosphodiesterase 4D (PDE4D) mRNA in the 3'-UTR region, which subsequently leads to a decrease in Pde4d expression in I/R N2a cells. CONCLUSIONS: Our results provide new ideas for the study of the mechanism of cerebral ischemia/reperfusion injury, and lay the foundation for further research on the treatment of brain I/R injury. Upregulation of miR-219a-5p decreases cerebral ischemia/reperfusion injury by targeting Pde4d in vitro.

[Research progress on effect of AP2/ERF transcription factors in regulating secondary metabolite biosynthesis].

AP2/ERF transcription factor is a kind of transcription factors widely existing in plants, and contains at least a conserved AP2/ERF domain composed of about 60-70 amino acids. AP2/ERF transcription factors are widely involved in a variety of physiological processes in plants, including plant development, fruit ripening, flower development and other plant development processes, as well as such stress response processes as damage, pathogen defense, high-salt condition and drought. In recent years, secondary metabolic engineering that takes transcription factors as genetic manipulation targets has developed rapidly in improving the content of active ingredients and the quality of medicinal plants. This paper reviews the recent progress in the regulation of secondary metabolites biosynthesis with AP2/ERF transcription factors, and provides theoretical basis for the exploration of efficient regulatory targets, the regulation of secondary metabolites in medicinal plants, the targeted improvement of the content of active ingredients in traditional Chinese medicine, and the sustainable supply of high-quality traditional Chinese medicines.

The immunomodulatory functions and molecular mechanism of a new bursal heptapeptide (BP7) in immune responses and immature B cells.

The bursa of Fabricius (BF) is the acknowledged central humoural immune organ unique to birds and plays a vital role in B lymphocyte development. In addition, the unique molecular immune features of bursal-derived biological peptides involved in B cell development are rarely reported. In this paper, a novel bursal heptapeptide (BP7) with the sequence GGCDGAA was isolated from the BF and was shown to enhance the monoclonal antibody production of a hybridoma. A mouse immunization experiment showed that mice immunized with an AIV antigen and BP7 produced strong antibody responses and cell-mediated immune responses. Additionally, BP7 stimulated increased mRNA levels of sIgM in immature mouse WEHI-231 B cells. Gene microarray results confirmed that BP7 regulated 2465 differentially expressed genes in BP7-treated WEHI-231 cells and induced 13 signalling pathways and various immune-related functional processes. Furthermore, we found that BP7 stimulated WEHI-231 cell autophagy and AMPK-ULK1 phosphorylation and regulated Bcl-2 protein expression. Finally, chicken immunization showed that BP7 enhanced the potential antibody and cytokine responses to the AIV antigen. These results suggested that BP7 might be an active biological factor that functions as a potential immunopotentiator, which provided some novel insights into the molecular mechanisms of the effects of bursal peptides on immune functions and B cell differentiation.

Glutathione S-Transferase Pi is Involved in the Growth of Mice.

Glutathione S-transferase Pi (GSTpi) is the most important subtribe of GSTs protein superfamily, and plays an important role in the process of detoxification, antioxidant and antiinflammation. Here we use a GSTpi inhibitor, 6-(7-nitro-2, 1, 3-benzoxadiazol-4-ylthio) hexanol (NBDHEX), to evaluate the effect of GSTpi on the growth of mice. Mice treated with NBDHEX have heavier weight and longer length. But there is no significant difference in ratios of the weights of brain, kidney, lung, spleen, liver and heart to the whole body weight and Lee's index between NBDHEX and control mice. These data suggested that GSTpi might inhibit mouse growth. Enzyme-linked immunosorbent assay (ELISA) showed that GSTpi inhibition induced a significant increase of growth hormone (GH) levels in blood and pituitary and insulin-like growth factor (IGF-1) levels in liver and blood in mice. Further observation demonstrated that GSTpi negatively regulated GHJanus Kinase 2 (JAK2)-signal transducer and activator of transcription 5 (STAT5) axis through inhibiting STAT5 phosphorylation, and as a result of GSTpi decreased the expression of IGF-1.

[Bioinformation analysis of chorismate synthase in Baphicacantus cusia and other 78 species of plants].

Chorismate synthase(CS, EC:4.2.3.5) catalyses 5-enolpyruvy-shikimate-3-phosphate to form chorismate, which is the essential enzyme for chorismate biosynthesis in organisms. The amino acid sequences of CS from 79 species of higher plants were reported in GenBank at present. 125 amino acid sequences of CS from Baphicacanthus cusia and other 78 species of plants were predicted and analyzed by using various bioinformatics software, including the composition of amino acid sequences, signal peptide, leader peptide, hydrophobic/hydrophilic, transmembrane structure, coiled-coil domain, protein secondary structure, tertiary structure and functional domains. The phylogenetic tree of CS protein family was constructed and divided into eight groups by phylogenetic analysis. The homology comparison indicated that B. cusia shared a high homology with several plants such as Sesamum indicum, Nicotiana tabacum, Solanum tuberosum and so on. The open reading frame(ORF) of all samples is about 1 300 bp, the molecular weight is about 50 kDa, the isoelectric point(pI) is 5.0-8.0 which illustrated that CS protein is slightly basic. The ORF of CS we cloned in B. cusia is 1 326 bp, the amino acid residues are 442, the molecular weight is 47 kDa and pI is 8.11. The CS in B.cusia showed obvious hydrophobicity area and hydrophilicity area, no signal peptide, and may exists transmembrane structure areas. The main secondary structures of CS protein are random coil and Alpha helix, also contain three main structural domains which are an active structural domain, a PLN02754 conserved domain and a FMN binding site. The acquired information in this study would provide certain scientific basis for further study on structure-activity relationship and structure modification of CS in plants in the future.

Omega-3 polyunsaturated fatty acids ameliorate ethanol-induced adipose hyperlipolysis: A mechanism for hepatoprotective effect against alcoholic liver disease.

Alcohol exposure induces adipose hyperlipolysis and causes excess fatty acid influx into the liver, leading to alcoholic steatosis. The impacts of omega-3 polyunsaturated fatty acids (n-3 PUFA) on ethanol-induced fatty liver are well documented. However, the role of n-3 PUFA in ethanol-induced adipose lipolysis has not been sufficiently addressed. In this study, the fat-1 transgenic mice that synthesizes endogenous n-3 from n-6 PUFA and their wild type littermates with an exogenous n-3 PUFA enriched diet were subjected to a chronic ethanol feeding plus a single binge as model to induce liver injury with adipose lipolysis. Additionally, the differentiated adipocytes from 3T3-L1 cells were treated with docosahexaenoic acid or eicosapentaenoic acid for mechanism studies. Our results demonstrated that endogenous and exogenous n-3 PUFA enrichment ameliorates ethanol-stimulated adipose lipolysis by increasing PDE3B activity and reducing cAMP accumulation in adipocyte, which was associated with activation of GPR120 and regulation of Ca2+/CaMKKß/AMPK signaling, resultantly blocking fatty acid trafficking from adipose tissue to the liver, which contributing to ameliorating ethanol-induced adipose dysfunction and liver injury. Our findings identify that endogenous and exogenous n-3 PUFA enrichment ameliorated alcoholic liver injury by activation of GPR120 to suppress ethanol-stimulated adipose lipolysis, which provides the new insight to the hepatoprotective effect of n-3 PUFA against alcoholic liver disease.

[Clinical Application of Improved Contrast Examination of Upper Gastrointestinal Tract].

Objective: To observe the effect of modified method of contrast examination of upper gastrointestinal tract, and explore the application value. Methods: 100 patients were examined with modified upper gastrointestinal barium radiography. Then compare it with conventional contrast. Results: The excellent rate of improved uppers gastrointestinal barium radiography was 87%, while the excellen rate of conventional contrast was 66%. The differences was statistically significant. Compared with the control group, improved upper gastrointestinal barium radiography provides high-resolution and high-contrast images. Conclusion: The improved upper gastrointestinal barium double contrast radiography is provided with simple operation, and the structure of gastrointestinal tissue is clearly shown improving the definitive diagnosis rate of diseases.

[Efficacy of glucocorticoids combined with immunoglobulin in initial treatment of Kawasaki disease: a Meta analysis].

OBJECTIVE: To systematically investigate the efficacy and safety of glucocorticoids (GCs) combined with intravenous injection of immunoglobulin (IVIG) in the initial treatment of Kawasaki disease (KD). METHODS: EDLINE Database, PubMed Database, CNKI, Wanfang Data, and VIP Database were searched to collect prospective or retrospective controlled studies on the combination of GCs and IVIG as the initial treatment of KD, which were published up to March 2016. Two investigators independently screened the literature, extracted data, and assessed the quality of the articles included. Then, a Meta analysis was performed using RevMan 5.2 software. RESULTS: A total of 11 articles in English were included, with 7 prospective studies and 4 retrospective studies. The results of the Meta analysis showed that compared with the group using IVIG alone, the combination group had a significantly lower incidence rate of coronary artery lesion (CAL) (OR=0.44, 95%CI 0.23-0.86, P=0.02) and a significantly shorter duration of fever (MD=-1.66, 95%CI -2.32 to -1.01, P<0.00001). The combination group had a significantly lower rate of no response to initial treatment than the IVIG alone group (OR=0.37, 95%CI 0.27-0.51, P<0.00001). The recurrence rate of KD and the incidence rate of adverse events showed no significant differences between the two groups. CONCLUSIONS: GCs combined with IVIG as the initial treatment for KD can reduce the incidence rate of CAL and the rate of no response to initial treatment and shorten the duration of fever, and does not increase the recurrence rate of KD and the incidence rate of adverse events.

GSTpi protects against angiotensin II-induced proliferation and migration of vascular smooth muscle cells by preventing signal transducer and activator of transcription 3 activation.

Angiotensin II (Ang II)-elicited excessive proliferation, hypertrophy and migration of vascular smooth muscle cells (VSMCs) are vital to the pathogenesis of atheroclerosis. Glutathione S-transferase pi (GSTpi) exists extensively in various kinds of cells and protects cells against different stresses. However, knowledge remains limited about what GSTpi acts in VSMCs. We investigated the effect of GSTpi on Ang II-induced VSMC proliferation, hypertrophy and migration and its latent mechanism. Overexpression and RNAi experiments demonstrated that GSTpi inhibited Ang II-induced proliferation, hypertrophy and migration of VSMCs and arrested progression of cell cycle from G0/G1 to S phase. Immunoprecipitation, mass spectrometry and confocal microscopy analyses showed that GSTpi directly associated with signal transducer and activator of transcription 3 (STAT3) to prevent Ang II-triggered binding of Src to STAT3 and thus suppressed Ang II-stimulated phosphorylation and nuclear translocation of STAT3, as well as cyclin D1 expression. In contrast, GSTpi didn't affect Ang II-activated extracellular signal-regulated kinase (ERK1/2). GSTpi acts as a negative regulator to prevent Ang II-triggered proliferative signaling in VSMCs, suggesting that it may protect vessels against the stresses associated with atherosclerosis formation.

Luteolin exhibits anti-inflammatory effects by blocking the activity of heat shock protein 90 in macrophages.

Septic diseases represent the prevalent complications in intensive care units. Luteolin, a plant flavonoid, has potent anti-inflammatory properties; however, the molecular mechanism beneath luteolin mediated immune modulation remains unclear. Here in vitro investigations showed that luteolin dose-dependently inhibited LPS-triggered secretion and relocation of high mobility group B-1 (HMGB1) and LPS-induced production of tumor necrosis factor alpha (TNF-α) and nitric oxide (NO) in macrophages. The mechanism analysis demonstrated that luteolin reduced the release of HMGB1 through destabilizing c-Jun and suppressed HMGB1-induced aggravation of inflammatory cascade through reducing Akt protein level. As an inhibitor of Hsp90, luteolin destabilized Hsp90 client protein c-Jun and Akt. In vivo investigations showed that luteolin effectively protected mice from lipopolysaccharide (LPS)-induced lethality. In conclusion, the present study suggested that luteolin may act as a potential therapeutic reagent for treating septic diseases.

BP5 regulated B cell development promoting anti-oxidant defence.

Bursa of Fabricius is the humoral immune system for B cell differentiation and antibody production. Bursopentine (BP5) is a novel immunomodulatory peptide and significantly stimulated an antigen-specific immune response in mice. BP5 was also found to protect LPS-activated murine peritoneal macrophages from oxidative stress. In this study, the effects of BP5 on B cell development were examined. The results suggested that BP5 markedly promoted B cell development by increasing CFU-pre B, and affected the redox homeostasis regulation of B cells. To study the molecular mechanism of effect of bursal-derived BP5, this research utilized 2D-E and MALDI-TOF/TOF to analyze the differentially expressed proteins of BP5-treated WEHI-231 cells. The results showed that BP5 affected the redox homeostasis regulation of WEHI-231 cells and induced alterations in the protein expression profiles related to the oxidoreduction coenzyme metabolic process, precursor metabolites and energy, proteolysis, RNA splicing and translation and cellular process, respectively. BP5 also induced glucose-6-phosphate dehydrogenase (G6PD) activity, an essential anti-oxidant cofactor. We found that the redox homeostasis regulation effect of BP5 was reduced in G6PD-deficient cells. These data suggested that BP5 affected the redox balance toward reducing conditions by promoting the expression of G6PD, which in turn regulated the glutathione redox cycle and other processes.

BP8, a novel peptide from avian immune system, modulates B cell developments.

The bursa of Fabricius (BF) is the key humoral immune organ unique to birds, and is critical for early B-lymphocyte proliferation and differentiation. However, the molecular basis and mechanisms through which the BF regulates B cell development are not fully understood. In this study, we isolated and identified a new bursal peptide (BP8, AGHTKKAP) by RP-HPLC and MALDI-TOF-MS. BP8 promoted colony-forming pre-B formation, bound B cell precursor, regulated B cell development in vitro as well as in vivo, upstream of the EBF-E2A-Pax5 regulatory complex and increased immunoglobulin secretion. These data revealed a bursal-derived multifunctional factor BP8 as a novel biomaterial which is essential for the development of the immune system. This study elucidates further the mechanisms involved in humoral immune system and has implications in treating human diseases.

Triterpenoid saponins from the roots of Clematis uncinata.

Eight new bisdesmosidic triterpenoid saponins, clematiunicinosides A-H (1-8), along with eleven known ones (9-19), were isolated from the roots of Clematis uncinata. Their structures were elucidated on the basis of spectroscopic analysis and chemical evidence. All the isolated saponins were tested for their cytotoxic activities on human caski cervical cancer (Caski) cells, and compounds 13, 17 and 19 exhibited inhibitory effect on Caski cells.

RBM25 is required to restrain inflammation via ACLY RNA splicing-dependent metabolism rewiring.

Spliceosome dysfunction and aberrant RNA splicing underline unresolved inflammation and immunopathogenesis. Here, we revealed the misregulation of mRNA splicing via the spliceosome in the pathogenesis of rheumatoid arthritis (RA). Among them, decreased expression of RNA binding motif protein 25 (RBM25) was identified as a major pathogenic factor in RA patients and experimental arthritis mice through increased proinflammatory mediator production and increased hyperinflammation in macrophages. Multiomics analyses of macrophages from RBM25-deficient mice revealed that the transcriptional enhancement of proinflammatory genes (including Il1b, Il6, and Cxcl10) was coupled with histone 3 lysine 9 acetylation (H3K9ac) and H3K27ac modifications as well as hypoxia inducible factor-1α (HIF-1α) activity. Furthermore, RBM25 directly bound to and mediated the 14th exon skipping of ATP citrate lyase (Acly) pre-mRNA, resulting in two distinct Acly isoforms, Acly Long (Acly L) and Acly Short (Acly S). In proinflammatory macrophages, Acly L was subjected to protein lactylation on lysine 918/995, whereas Acly S did not, which influenced its affinity for metabolic substrates and subsequent metabolic activity. RBM25 deficiency overwhelmingly increased the expression of the Acly S isoform, enhancing glycolysis and acetyl-CoA production for epigenetic remodeling, macrophage overactivation and tissue inflammatory injury. Finally, macrophage-specific deletion of RBM25 led to inflammaging, including spontaneous arthritis in various joints of mice and inflammation in multiple organs, which could be relieved by pharmacological inhibition of Acly. Overall, targeting the RBM25-Acly splicing axis represents a potential strategy for modulating macrophage responses in autoimmune arthritis and aging-associated inflammation.

Role of Th2, Th17 and Treg Cells and relevant cytokines in pathogenesis of allergic rhinitis.

OBJECTIVE: To explore the role of different cells and molecules in the pathogenesis of allergic rhinitis (AR) with positive Artemisia allergen by detecting their expression levels. METHODS: From January 2021 to December 2022,200 AR patients diagnosed in the Otolaryngology Clinic of Ordos Central Hospital were selected as the AR group, and 50 healthy people who underwent physical examination in the hospital during the same period were randomly selected as the healthy control (HC) group. The levels of GATA-3mRNA, RORγtmRNA and FoxP3mRNA in peripheral blood mononuclear cells were detected by real-time fluorescence quantitative PCR (qRT-PCR). The proportions of Th2, Th17 and Treg cells were detected by flow cytometry. The concentrations of IL-4, IL-5, IL-17 and IL-10 in serum were detected by enzyme-linked immunosorbent assay. The differences of transcription gene level, immune cell ratio and cytokine concentration between the two groups were analyzed. RESULTS: There was no difference in age and gender between the two groups. The levels of GATA-3mRNA and RORγtmRNA transcription genes in peripheral blood mononuclear cells, the percentage of Th2, Th17 and Treg immune cells, the levels of eosinophils and basophils in peripheral blood, the concentrations of IL-4, IL-5, IL-17, IL-10 cytokines and IgE in serum of AR patients were significantly higher than those in HC group (P < 0.05). IL-4 and IL-17 were positively correlated with total IgE level. CONCLUSION: The secretion of immune cells and cytokines in peripheral blood of AR patients is abnormal. Th2, Th17, Treg specific transcription factors and related cells and cytokines are involved in the occurrence and development of allergic rhinitis.

Identification and characterization of novel immunomodulatory bursal-derived pentapeptide-II (BPP-II).

The bursa of Fabricius, the acknowledged central humoral immune organ, plays a vital role in B lymphocyte differentiation. However, there are few reports of the molecular basis of the mechanism on immune induction and potential antitumor activity of bursal-derived peptides. In this paper, a novel bursal-derived pentapeptide-II (BPP-II, MTLTG) was isolated and exerted immunomodulatory functions on antibody responses in vitro. Gene microarray analyses demonstrated that BPP-II regulated expression of 2478 genes in a mouse-derived hybridoma cell line. Immune-related gene ontology functional procedures were employed for further functional analysis. Furthermore, the majority of BPP-II-regulated pathways were associated with immune responses and tumor processes. Moreover, BPP-II exhibited immunomodulatory effects on antigen-specific immune responses in vivo, including enhancement of avian influenza virus (H9N2 subtype)-specific antibody and cytokine production and modification of T cell immunophenotypes and lymphocyte proliferation. Finally, BPP-II triggered p53 expression and stabilization and selectively inhibited tumor cell proliferation. These data identified the multifunctional factor, BPP-II, as a novel biomaterial representing an important linking between the humoral central immune system and immune induction, including antitumor. Information generated in this study elucidates further the mechanisms involved in humoral immune system and represents the potential basis of effective immunotherapeutic strategies for treating human tumors and immune improvement.