Melittin exhibits high antibacterial potency against drug-resistant bacteria. However, the clinical utility of melittin is limited by its serious hemolytic activity. Thus, the need for developing novel melittin analogues with high antimicrobial activity and low hemolytic activity has grown. We designed, synthesized, and evaluated 20 novel melittin analogues with varying hydrophobic, polar or positively charged amino acids. The results showed that 8 compounds had antimicrobial activity (MIC: 1-4 μg·mL^-1) against gram-positive pathogens equal to or better than that of melittin, and 16 compounds had low hemolytic activity (HC₅₀ ≥ 11.9 μg·mL^-1). Compounds 13 (MIC: 2-4 μg·mL^-1) and 15 (MIC: 1-2 μg·mL^-1) showed equal or better antimicrobial activity against both susceptible and resistant strains of Staphylococcus aureus and Enterococcus faecium compared to melittin (MIC: 4 μg·mL^-1). Compound 13 (HC₅₀: 24.0 ± 4.3 μg·mL^-1) displayed noticeably decreased hemolytic activity compared to melittin (HC₅₀: 5.3 ± 0.4 μg·mL^-1). This work established a base for further study on the structure-activity relationships and structure-toxicity relationships of melittin.

Autistic traits including social reciprocal deficits, communication deficits and stereotyped behaviors, are manifested not only in patients with autism spectrum disorders (ASD) and their families, but also in general population. In recent years, there has much research related to autistic traits. This article summarizes research advance of autistic traits in ASD relations and general population.
Child Development Disorders, Pervasive ; diagnosis ; Humans ; Magnetic Resonance Imaging ; Phenotype ; Severity of Illness Index ; Surveys and Questionnaires

OBJECTIVETo establish a nasopharyngeal carcinoma (NPC) cell line with stable EIF4G1 gene silencing induced by small interfering RNA (siRNA).

METHODSThe EIF4G1 mRNA levels in 8 NPC cell lines including 5-8F, 6-10B, C666-1, CNE1, CNE2, HNE1, HONE1, and SUNE1 were detected by fluorescence quantitative RT-PCR (QRT-PCR). The recombinant lentivirus shRNA expression plasmid targeting EIF4G1 gene was packaged into mature lentivirus by 293FT cells and used to infect 5-8F cells. After blasticidin selection of NPC cells with constant expression of the EIF4G1-siRNA, the efficiency of EIF4G1 mRNA expression interference was determined using QRT-PCR.

RESULTSThe 8 NPC cell lines showed differential expression of EIF4G1 mRNA, among which 5-8F cells had the highest EIF4G1 expression. The recombinant lentivirus plasmid pLenti6/BLOCK-iT-DEST/EIF4G1-shRNA was successfully constructed and verified by PCR and sequencing. The EIF4G1 mRNA level of 5-8F cells infected with shRNA-EIF4G1 lentivirus was significantly reduced as compared with the negative control and the blank control cells.

CONCLUSIONThe recombinant lentivirus vector pLenti6/BLOCK- iT-DEST/EIF4G1-shRNA we constructed results in marked downregulation of EIF4G1 mRNA expression and constant expression of EIF4G1-siRNA after infection of 5-8F cells.

Cell Line, Tumor ; Eukaryotic Initiation Factor-4G ; biosynthesis ; genetics ; Genetic Vectors ; genetics ; Humans ; Lentivirus ; genetics ; metabolism ; Nasopharyngeal Neoplasms ; genetics ; metabolism ; RNA Interference ; RNA, Messenger ; biosynthesis ; genetics ; RNA, Small Interfering ; genetics ; Transfection

Aim To investigate the effect of broneol on acute lung injury(ALI) induced by lipopolysaccharide (LPS). Methods Male C57 mice were randomly di-vided into saline group, model group, broneol group and dexamethasone group, then the ALI mouse model was induced by instilling intratracheally with LPS. The levels of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),interleukin-6(IL-6) and keratinocyte-de-rived cytokine (KC) were measured at 6h, 12h and 24h after instillation of LPS, and the pathological changes of lung were observed. Mice alveolar macro-phages (MHS) and epithelial cells (MLE-12) were stimulated by LPS. After the stimulation of 1h, 3h, 6h,9h, 12h, 24h, the levels of TNF-α and IL-6 in MHS cells and the contents of KC and macrophage in-flammatory protein-2 (MIP-2) in MLE-12 cells were measured. Results Broneol could inhibit the secre-tion of TNF-α,KC and IL-1β;the early effect of bro-neol on IL-6 was not obvious,but the later effect after the treatment of 24 hours was obvious. After LPS instil-lation 6h and 12h,Broneol could significantly improve lung tissue pathological changes. Broneol had no effect on TNF-α secretion of MHS cells, but it obviously af-fected IL-6 secretion in the later stage. In addition, broneol significantly inhibited KC and MIP2 secretion in MLE-12 cells at the later stage of LPS stimulation. Conclusions Broneol can protect LPS-induced acute lung injury. The mechanism may be related to the inhi-bition of the release of inflammatory factors,the activa-tion of inflammatory cells and the aggregation of neutro-phils.

OBJECTIVES: To explore the casual relationship and the significance of identification among the injury, disease and damage consequence in the disability evaluation of lumbar spondylolysis by the standard for identifying grading of disability caused by work-related injuries. METHODS: The general data, injury manner, clinical treatment and the imaging examination of 32 lumbar spondylolysis cases were collected and retrospectively analyzed. According to the degree of participation in the injury and damage consequence, the identification and assessment of casual relationship was made, and the grading of disability was assessed. RESULTS: For 32 cases, injury had no effect on damage consequence in 7 cases, slight effect in 5 cases, secondary effect in 13 cases, equivalent effect in 4 cases, and complete effect in 3 cases. According to the related items in the standard for identifying grading of disability caused by work-related injuries, 3 cases were rated level 7, 5 cases were level 8, 6 cases were level 9, 11 cases were level 11 among the cases which existed causal relationship. CONCLUSIONS The formation of lumbar spondylolysis is connected to the factors of age, anatomy, occupation and injury manner etc. The degree of disability should be accessed comprehensively after the analysis of the casual relationship among the injury, disease and damage consequence.
Disability Evaluation ; Female ; Humans ; Lumbar Vertebrae/pathology* ; Retrospective Studies ; Spondylolysis/pathology*

Objective: To explore susceptibility genes for autism spectrum disorders (ASD). Methods: Whole-exome sequencing was carried out for 60 family trios affected with sporadic ASD. Genetic variants discovered in over 10% of the patients were selected for genotype-phenotype correlation and pathway enrichment analysis using Phenolyzer software and metascape database. Combining gene-phenotypic scores, pathway-related genes associated with neural and neurite triggering were screened for the candidates. Results: A total of 170 common variants were found to be associated with the ASD phenotype. Among these, there was only one high-confidence gene [SHANK2 (0.8146)] and four medium-confidence genes [ERBB2 (0.1322), LAMC3 (0.1117), PPFIA4 (0.1059), DISC1 (0.1002)]. Twenty-pathways and four biological processes were found to be statistically significant by pathway enrichment analysis, which included neuron projection morphogenesis (GO: 0048812), regulation of neuroblast proliferation (GO: 1902692), modulation of excitatory postsynaptic potential (GO: 0098815), and dendrite morphogenesis (GO: 0048813). Twenty-one genes were found to be closely associated with neurological and neurite triggering, among which only SHANK2, ERBB2, and DISC1 had above-medium confidence correlation scores with the ASD phenotypes. Conclusion Abnormal neuron projection morphogenesis (GO: 0048812) may be closely related to the occurrence of ASD. SHANK2, ERBB2, and DISC1 are susceptibility genes for ASD.

OBJECTIVEThe sex therapy is not yet popularized at present. This study aimed to evaluate the effect of the combination of the improved sex therapy and oral sildenafil on erectile dysfunction (ED).

METHODSA total of 3130 Uigur cases of ED received in Xinjiang Bogda Hospital were divided into a control group (n=625) and a trial group (n=2505), the former treated with oral sildenafil alone, and the latter by the combination of the improved genital therapy and sildenafil, both for 3 months and followed up at 6 and 12 months after the treatment. The therapeutic effects were evaluated and compared using IIEF-5.

RESULTSThe IIEF-5 scores of the control group were 12.80 +/- 3.76 and 18.10 +/- 2.61 before and after the treatment, and 17.35 +/- 2.73 and 16.64 +/- 2.63 at 6 and 12 months, respectively, while those of the trial group were 12.73 +/- 3.52 and 19.06 +/- 4.07 before and af- ter the treatment, and 19.86 +/- 2.42 and 20.47 +/- 2.38 at 6 and 12 months, respectively, with statistically significant differences either between pre- and post-treatment (P < 0.05) or between the control and trial groups at 6 and 12 months (P < 0.05).

CONCLUSIONThe combination of the improved sex therapy and oral sildenafil is superior to sildenafil alone in the treatment of ED, and its efficacy is relatively stable at 12 months.

Adult ; Aged ; Asian Continental Ancestry Group ; Erectile Dysfunction ; drug therapy ; ethnology ; Humans ; Male ; Middle Aged ; Piperazines ; therapeutic use ; Purines ; therapeutic use ; Retrospective Studies ; Sildenafil Citrate ; Sulfones ; therapeutic use ; Treatment Outcome ; Young Adult

OBJECTIVE: To explore the effect of acupuncture on oxidative stress and apoptosis-related proteins of liver in obese mice induced by high-fat diet. METHODS: A total of 45 male C57BL/6 mice were randomized into a control group (10 mice) and a model established group (35 mice). Mice in the model established group were fed with high-fat diet for 16 weeks to establish the obesity model. After model established, 30 mice were randomized into a model group, a non-acupoint group and an acupoint group, 10 mice in each one. Acupuncture was applied at "Guanyuan" (CV 4), " Zusanli" (ST 36), "Yishu" (EX-B 3) in the acupoint group and the points of 0.5 cm and 1 cm to the base of tail in the non-acupoint group, 15 min each time, once a day for 8 weeks. Mice in the control group were fed with normal diet, while mice in the other 3 groups were fed with high-fat diet continuously for 8 weeks. The body weight was measured at 0, 4th, 8th, 12th, 16th, 20th, 24th week in each group respectively. After 24-week intervention, the weight of white adipose tissue of epididymis and perirenal and liver was measured; the levels of serum alanine transaminase(ALT) and glutamic oxaloacetic aminotransferase (AST) were detected by automatic biochemical analyzer; liver homogenate was used to detect the level of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD); the liver morphology was observed by HE staining; the expression of apoptosis-related proteins Bax and Bcl-2 were detected by Western blot. RESULTS: Compared with the control group, the body weight of mice in the model group, the acupoint group and the non-acupoint group was decreased on 16th week into experiment (before intervention, <0.05); compared with the model group and the non-acupoint group, the body weight of mice in the acupoint group were decreased after intervention (<0.05). Compared with the control group, the weight of white adipose tissue and liver, the levels of serum ALT and AST, the level of liver MDA, the expression of liver Bax were increased (<0.05); the activity of liver SOD and the expression of liver Bcl-2 were decreased in the model group after intervention (<0.05). Compared with the model group and the non-acupoint group, the weight of white adipose tissue and liver, the levels of serum ALT and AST, the level of liver MDA, the expression of liver Bax were decreased (<0.05); the activity of liver SOD and the expression of liver Bcl-2 were increased in the acupoint group after intervention (<0.05). CONCLUSION Acupuncture at "Guanyuan" (CV 4), "Zusanli" (ST 36) and "Yishu"(EX-B 3) can improve obesity and obesity related hepatic disorder by regulating oxidative stress and inhibiting apoptosis in liver.

Daphnetin is quickly eliminated in rats after dosing, but the mechanism remains unclear. This study was aimed to investigate the in vitro metabolism of daphnetin using rat liver S9 fractions (RLS9). The metabolites formed in RLS9 were identified and the kinetic parameters for different metabolic pathways were determined. HPLC-DAD-MS analysis showed that daphnetin was biotransformed to six metabolites, which were identified as 7 or 8 mono-glucuronide and mono-sulfate, 8-methylate, and 7-suflo-8-methylate. Methylation and glucuronidation of daphnetin exhibited the Michaelis-Menten kinetic characteristics, whereas the substrate inhibition kinetic and the two-site kinetic were observed for 8-sulfate and 7-sulfate formations. Of the 3 conjugation pathways, the intrinsic clearance rate for sulfation was highest, followed by methylation and glucuronidation. By in vitro-in vivo extrapolation of the kinetic data measured in RLS9, the hepatic clearance were estimated to be 54.9 mL·min^-1·kg^-1 which is comparable to the system clearance (58.5 mL·min^-1·kg^-1) observed in rats. In conclusions, the liver might be the main site for daphnetin metabolism in rats. Sulfation, methylation and glucuronidation are important pathways of the hepatic metabolism of daphnetin in rats.

Aim To investigate the expression of Foxos in human umbilical vein endothelial cells(HUVECs)with insulin resistance(IR)induced by high glucose and high fat(HG/HF)stress and its significance.Methods First, the IR model of endothelial cells was established by HG /HF stress.The differential expression of Foxos gene in normal(Ctrl )group and HG /HF group was observed, and the subtypes with the most significant changes in Foxos were screened out, such as Foxo6.Next, Foxo6 was silenced to observe its role in endothelial cell with IR.Finally, whether the mechanism of Foxo6-mediated IR was related to the interaction of NF-κB signaling was investigated.Results The expression increase of Foxo6 was the most significant among Foxos under the IR condition induced by HG/HF.Using a small RNA interference and plasmid transfection technique, we found that the silence effect of the siRNA3 fragments targeting Foxo6 was the most significant among the siRNAs.Moreover, the further study showed that silencing the Foxo6 gene could significantly reverse the endothelial IR induced by HG/HF, and the mechanism of the reversal effect was related to the interaction between the Foxo6 and NF-κB signal.Conclusions Foxo6 mediates the endothelial cell IR induced by the HG /HF stress.The underlying mechanism is that Foxo6 can interact with NF-κBp65 and activate NF-κB signaling pathway.Silencing Foxo6 can improve the IR of vascular endothelial cells induced by HG /HF stress.