Guided by molecular networking, nine novel curvularin derivatives (1-9) and 16 known analogs (10-25) were isolated from the hydrothermal vent sediment fungus Penicillium sp. HL-50. Notably, compounds 5-7 represented a hybrid of curvularin and purine. The structures and absolute configurations of compounds 1-9 were elucidated via nuclear magnetic resonance (NMR) spectroscopy, X-ray diffraction, electronic circular dichroism (ECD) calculations, ¹³C NMR calculation, modified Mosher's method, and chemical derivatization. Investigation of anti-inflammatory activities revealed that compounds 7-9, 11, 12, 14, 15, and 18 exhibited significant suppressive effects against lipopolysaccharide (LPS)-induced nitric oxide (NO) production in murine macrophage RAW264.7 cells, with IC₅₀ values ranging from 0.44 to 4.40 μmol·L^-1. Furthermore, these bioactive compounds were found to suppress the expression of inflammation-related proteins, including inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), NLR family pyrin domain-containing protein 3 (NLRP3), and nuclear factor kappa-B (NF-κB). Additional studies demonstrated that the novel compound 7 possessed potent anti-inflammatory activity by inhibiting the transcription of inflammation-related genes, downregulating the expression of inflammation-related proteins, and inhibiting the release of inflammatory cytokines, indicating its potential application in the treatment of inflammatory diseases.
Penicillium/chemistry* ; Mice ; Animals ; Anti-Inflammatory Agents/isolation & purification* ; RAW 264.7 Cells ; Nitric Oxide/metabolism* ; Hydrothermal Vents/microbiology* ; Macrophages/immunology* ; Molecular Structure ; Nitric Oxide Synthase Type II/immunology* ; Cyclooxygenase 2/immunology* ; Geologic Sediments/microbiology* ; NF-kappa B/immunology* ; NLR Family, Pyrin Domain-Containing 3 Protein/immunology*

Objective To develop an ultra high performance liquid chromatography-mass spectrometry(UPLC-MS)method for quantifying serum levels of norepinephrine(NE)and 5-hydroxytryptamine(5-HT),and to monitor the dynamic changes in these neurotransmitters during the process of establishing a model of acute reserpine-induced depression-like mice.Methods By evaluating matrix effect,recovery,precision,and accuracy efficiency,an UPLC-MS method for determining the concentrations of NE and 5-HT in serum was established.Forty-eight C57 mice were randomly divided into normal control and model groups,which were intraperitoneally injected with physiological saline(10 mL/kg)and reserpine(2.5 mg/kg),respectively.At various time points after intraperitoneal injection,the degree of ptosis and decreases in body temperature of the mice were observed before orbital blood was sample for the determination of NE and 5-HT levels.Results The concentrations of NE and 5-HT showed good linearity within the range of 15.63 to 2000.00 ng/mL,with R2 values greater than 0.999.The results of methodological validation met the requirements for the analysis of biological samples,with a lower limit of quantification of 15.63 ng/mg.After intraperitoneal injection of reserpine,the model mice exhibited varying body temperature decreases and ptosis.At 1 and 2 h post-administration,the depression-like symptoms in the model group were significantly different from those of the normal control group(P＜0.01).The body temperature of mice in the model group was significantly lower than that of mice in the normal control group(P＜0.01),while the score of the eyelid ptosis was significantly higher(P＜0.001).The levels of NE and 5-HT in the serum of model mice were also significantly depleted,and were significantly different from those of the normal control group at 0.5,1 and 2 h(P＜0.05).Conclusion The study process of established a rapid and accurate method for dynamically observing the changes in NE and 5-HT levels during the process of establishing a model of acute reserpine-induced depression-like mice,which might contribute to the study of the pathogenesis of depression and the development of new antidepressant drugs.

Objective To investigate the predicting value of cardiac magnetic resonance feature tracking(CMR-FT)for adverse left ventricular remodeling(ALVR)in patients with acute anterior wall ST-segment elevation myocardial infarction(STEMI).Methods The clinical data and cardiac magnetic resonance(CMR)images of 161 acute anterior wall STEMI patients within 1 week and 6 months after emergency percutaneous coronary intervention(PCI)were retrospectively analyzed.ALVR was defined as an increase of left ventricular end-diastolic volume(LVEDV)over 20％at the second CMR examination compared to the baseline.The CMR parame-ters were analyzed by CVI42 post-processing software.The logistic regression analysis was used to screen the independent predictors of ALVR,and the receiver operating characteristic(ROC)curve was used to evaluate the predictive efficiency of ALVR.Results The incidence of ALVR at 6 months was 21.7％(35/161).The logistic regression analysis showed that the left ventricular global circumferential strain(LVGCS)and right ventricular global longitudinal strain(RVGLS)at baseline were independent predictors for ALVR(P＜0.001).When LVGCS was-13.89％and RVGLS was-15.07％at baseline,the sensitivity of predicting ALVR was 0.714 and 0.743,the specificity was 0.833 and 0.810,and the area under the curve(AUC)was 0.806 and 0.835,respectively.The sensitivity of LVGCS combined with RVGLS in predicting ALVR was 0.802,the specificity was 0.952,and the AUC was 0.888.The DeLong test showed that the AUC of LVGCS com-bined with RVGLS in predicting ALVR was significantly higher than that of individuals,and the difference was statistically significant(P＜0.05).Conclusion The LVGCS and RVGLS at baseline are independent predictors for ALVR in patients with acute anterior wall STEMI,their combination can significantly improve the pre-dictive efficiency of ALVR in these patients.

Objective To investigate the predicting value of cardiac magnetic resonance feature tracking(CMR-FT)for adverse left ventricular remodeling(ALVR)in patients with acute anterior wall ST-segment elevation myocardial infarction(STEMI).Methods The clinical data and cardiac magnetic resonance(CMR)images of 161 acute anterior wall STEMI patients within 1 week and 6 months after emergency percutaneous coronary intervention(PCI)were retrospectively analyzed.ALVR was defined as an increase of left ventricular end-diastolic volume(LVEDV)over 20％at the second CMR examination compared to the baseline.The CMR parame-ters were analyzed by CVI42 post-processing software.The logistic regression analysis was used to screen the independent predictors of ALVR,and the receiver operating characteristic(ROC)curve was used to evaluate the predictive efficiency of ALVR.Results The incidence of ALVR at 6 months was 21.7％(35/161).The logistic regression analysis showed that the left ventricular global circumferential strain(LVGCS)and right ventricular global longitudinal strain(RVGLS)at baseline were independent predictors for ALVR(P＜0.001).When LVGCS was-13.89％and RVGLS was-15.07％at baseline,the sensitivity of predicting ALVR was 0.714 and 0.743,the specificity was 0.833 and 0.810,and the area under the curve(AUC)was 0.806 and 0.835,respectively.The sensitivity of LVGCS combined with RVGLS in predicting ALVR was 0.802,the specificity was 0.952,and the AUC was 0.888.The DeLong test showed that the AUC of LVGCS com-bined with RVGLS in predicting ALVR was significantly higher than that of individuals,and the difference was statistically significant(P＜0.05).Conclusion The LVGCS and RVGLS at baseline are independent predictors for ALVR in patients with acute anterior wall STEMI,their combination can significantly improve the pre-dictive efficiency of ALVR in these patients.

Objective To evaluate the protective effect of epigallocatechin-3-gallate(EGCG)on cisplatin(CIS)-induced acute kidney injury(AKI)in rats based on network pharmacology and in vivo animal model experiments.Methods Targets of EGCG and AKI were collected from the TCMSP,Gene Cards,and OMIM websites,and a protein-protein interaction network was constructed based on the intersection.The intersection targets were analyzed visually using Cytoscape 3.9.1 and the key targets were screened out.Kyoto Encyclopedia and of Genes and Genomes and Gene Ontology enrichment analyses were carried out using the DAVID database.Thirty-two male Wistar rats were divided randomly into four groups:CON group,EGCG group,CIS group,and CIS+EGCG group.Rats in the control and CIS groups were given normal saline every day,rats in the EGCG and CIS+EGCG groups were given EGCG(40 mg/kg)every day for 28 d,and rats in the CIS and CIS+EGCG groups received an intraperitoneal injection of CIS(7 mg/kg)on the 26th day.Blood and tissue samples were obtained on the 29th day.Serum urea nitrogen and creatinine levels were detected,renal pathology was observed by HE staining,and apoptosis in renal tissue was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling.Western Blot,qRT-PCR,and immunohistochemistry were used to verify the result.Results Eighty-seven genes intersecting EGCG and AKI and 25 core targets were screened from network pharmacology,which influenced the development of AKI via signal pathways such as PI3K/Akt and various biological processes.EGCG pretreatment significantly reduced serum levels of serum urea nitrogen and creatinine,improved the renal pathology,and reduced renal tissue apoptosis in AKI rats.Western Blot,qRT-PCR and immunohistochemistry showed that pretreatment with EGCG activated the PI3K/Akt pathway.Conclusions EGCG alleviates CIS-induced AKI in rats via the PI3K/Akt signaling pathway.

BACKGROUND: There have been many significant advances in the diagnosis and treatment of non-small cell lung cancer (NSCLC). However, the mechanism underlying the progression of NSCLC is still not clear. Plant homodomain finger-like domain-containing protein 5A (PHF5A) plays an important role in processes of chromatin remodeling, morphological development of tissues and organs and maintenance of stem cell pluripotency. This study aims to investigate the role of PHF5A in the proliferation and migration of NSCLC. METHODS: A549 and PC-9 PHF5A overexpression cell lines were constructed. PHF5A expression was decreased in H292 and H1299 cells by using siRNA. Flow cytometry was used to detect the cell cycle. MTT assay and clone formation assay were used to examine the proliferative ability of NSCLC, while migration assay and wound healing assay were performed to evaluate the ability of migration. Western blot analysis was used to measure the expressions of PI3K, p-AKT and the associated downstream factors. RESULTS: Up-regulation of PHF5A in A549 and PC-9 cells increased the proliferation rate, while down-regulation of PHF5A in H292 and H1299 cells inhibited the proliferation rate at 24 h, 48 h and 72 h (P<0.05). The metastatic ability was elevated in the PHF5A-overexpresion groups, while reduced in the PHF5A-down-regulation group (P<0.05). In addition, reduced expression of PHF5A induced cell cycle arrest at G1/S phase (P<0.05). Furthermore, decreased expression of PHF5A reduced the expression levels of PI3K, phosphorylation of AKT, c-Myc (P<0.05) and elevated the expression of p21 (P<0.05). CONCLUSIONS These results demonstrated that PHF5A may play an important role in progression of NSCLC by regulating the PI3K/AKT signaling pathway.
Humans ; Carcinoma, Non-Small-Cell Lung/pathology* ; Lung Neoplasms/pathology* ; Proto-Oncogene Proteins c-akt/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Cell Line, Tumor ; Cell Proliferation/genetics* ; Cell Movement/genetics* ; Gene Expression Regulation, Neoplastic ; Trans-Activators/genetics* ; RNA-Binding Proteins/metabolism*

Objective: To understand the epidemiological characteristics of outbreaks and analyze the genetic characteristics of the whole genome of influenza H3N2 virus among avian-human-swine, and to elaborate the source of influenza virus. Methods: The epidemic information was collected using the case investigation, the pharyngeal swab samples from influenza-like-illness cases were detected by real-time PCR and virus isolation. The phylogeny and molecular features of whole-genome were analyzed with EditSeq and MEGA 5.05 software. Results: The prevalence rate of this outbreak was 34.88%, 15 samples of throat swabs were collected, the positive rate of nucleic acid detection was 73.33%, 5 strains of seasonal influenza A (H3N2) influenza viruses were isolated. The phylogenetic analysis showed the eight gene segments of the isolated influenza viruses belonged to the same cluster with 2015-2016 influenza vaccine strain A/Switzerland/9715293/2013(H3N2), and no recombination was found. Compared with vaccine strain, 14 variant amino acids of protein of HA were identified, and 8 of them were located in antigenic sites. All strains were sensitive to neuraminidase inhibitors while they showed resistance to blockers of M2 ion channel. The glycosylation sites analysis showed that two new glycosylation sites NRT151-153 and NAT245-247were added. Conclusions The outbreak was caused by seasonal influenza A (H3N2) virus which had an antigenic drift and no genetic avian-human-swine recombination was found.

Quantitative calibration strategy as an essential issue in laser ablation ICP-MS plays an important role for the guarantee of analytical accuracy.In this study, uncertainties of reference values in current available glass certified reference materials (NIST, MPI-DING and USGS) as well as the matrix effect among them were systematically evaluated.The results illustrated that NIST610 was better than other reference materials from aspect of reference value uncertainty.The matrix effect among NIST, MPI-DING and USGS reference materials was insignificant under our experimental conditions.A quantification strategy based on two reference materials (NIST610 and StHs6/80-G) and normalization to 100% (w/w) was proposed to avoid the insufficiency of single reference material strategy, which suffered the very low content and large uncertainty for some elements.The comparision of ML3B-G results obtained from three quantification strategies (single reference material NIST610, single reference material StHs6/80-G and two refterence materials) illustrated that the proposed strategy improved the analytical accuracy.Three reference materials (BCR-2G, CGSG-2 and KL-2G) were quantified with the proposed strategy, and almost all data matched well with reference value, meanwhile the data reported here could supplement the reference value database.

Objective: To explore the relationship between fathers′ nursing time and maternal parenting stress of children with autism spectrum disorder(ASD). Method: Mothers of 98 ASD children who were first diagnosed in the department of Child Health Care, Children′s Hospital of Fudan University during June 2015 to January 2016 were included in the ASD group, with mothers of 92 typical children from a Community Maternal and Child Health Hospital and a kindergarten in the control group. The evaluation of parenting stress, parents′ nursing time and other related factors were cross-sectionally analyzed. Interview was conducted with the following tools: Parental Stress Index-Short Form(PSI-SF)for maternal parenting stress, and self-made General Parenting Information Questionnaire for nursing time of both parents and other related factors. The relationships were analyzed by Multiple Linear Regression analysis and Wilcoxon Rank-Sum test. Result: Maternal parenting stress of ASD children had a significant negative correlation with father′s nursing time in total score of parenting stress, PCDI domain and PD domain (t=-2.76, -2.98, -2.79; P=0.007, 0.004, 0.006), within which PD domain also included family annual income and mothers′ nursing time (R²=0.22, 0.24, 0.25); while no such correlation was found in control group in terms of father′s nursing time(P=0.22, 0.42, 0.06). Wilcoxon Rank-Sum test showed that in 62 (63.3%) double-income ASD families and 72(78.3%) double-income typical families, there were significant differences between ASD fathers′ and ASD mothers′and typical fathers′nursing time(2.0(0.5, 2.1)vs. 3.5(2.4, 6.0)vs. 3.0(2.0, 4.7)h, t=-86.32、-49.65, all P<0.01). Conclusion Lack of fathers′ involvements was common in ASD children′s families. Increasing these fathers′ nursing time, as well as their enthusiasm and initiative in the family intervention could relieve maternal parenting stress and improve the intervention pattern of ASD children.

The population of the very elderly is growing steeply with prolonged life expectancy.Age is an independent risk factor for stroke.Naturally,the very elderly become the high risky population.Hypertension is the most common and modifiable risk factor of stoke in the very elderly.Results of studies conducted during these 20 years have been reported to explore and investigate the relationship between stroke primary prevention and antihypertensive treatment,some of which are regarded as landmarks trials,providing essential evidences for blood pressure management in the very elderly.