Enhancing alfalfa photosynthetic performance through arbuscular mycorrhizal fungi inoculation across varied phosphorus application levels.

This study evaluated the effects of arbuscular mycorrhizal fungi inoculation on the growth and photosynthetic performance of alfalfa under different phosphorus application levels. This experiment adopts two-factors completely random design, and sets four levels of fungi application: single inoculation with Funneliformis mosseae (Fm, T1), single inoculation with Glomus etunicatum (Ge, T2) and mixed inoculation with Funneliformis mosseae × Glomus etunicatum (Fm×Ge, T3) and treatment uninfected fungus (CK, T0). Four phosphorus application levels were set under the fungi application level: P2O5 0 (P0), 50 (P1), 100 (P2) and 150 (P3) mg·kg-1. There were 16 treatments for fungus phosphorus interaction. The strain was placed 5 cm below the surface of the flowerpot soil, and the phosphate fertilizer was dissolved in water and applied at one time. The results showed that the intercellular CO2 concentration (Ci) of alfalfa decreased at first and then increased with the increase of phosphorus application, except for light use efficiency (LUE) and leaf instantaneous water use efficiency (WUE), other indicators showed the opposite trend. The effect of mixed inoculation (T3) was significantly better than that of non-inoculation (T0) (p < 0.05). Pearson correlation analysis showed that Ci was significantly negatively correlated with alfalfa leaf transpiration rate (Tr) and WUE (p < 0.05), and was extremely significantly negatively correlated with other indicators (p < 0.01). The other indexes were positively correlated (p < 0.05). This may be mainly because the factors affecting plant photosynthesis are non-stomatal factors. Through the comprehensive analysis of membership function, the indexes of alfalfa under different treatments were comprehensively ranked, and the top three were: T3P2>T3P1>T1P2. Therefore, when the phosphorus treatment was 100 mg·kg-1, the mixed inoculation of Funneliformis mosseae and Glomus etunicatum had the best effect, which was conducive to improving the photosynthetic efficiency of alfalfa, increasing the dry matter yield, and improving the economic benefits of local alfalfa in Xinjiang. In future studies, the anatomical structure and photosynthetic performance of alfalfa leaves and stems should be combined to clarify the synergistic mechanism of the anatomical structure and photosynthetic performance of alfalfa.

Analysis and validation of diagnostic biomarkers and immune cell infiltration characteristics in pediatric sepsis by integrating bioinformatics and machine learning.

BACKGROUND: Pediatric sepsis is a complicated condition characterized by life-threatening organ failure resulting from a dysregulated host response to infection in children. It is associated with high rates of morbidity and mortality, and rapid detection and administration of antimicrobials have been emphasized. The objective of this study was to evaluate the diagnostic biomarkers of pediatric sepsis and the function of immune cell infiltration in the development of this illness. METHODS: Three gene expression datasets were available from the Gene Expression Omnibus collection. First, the differentially expressed genes (DEGs) were found with the use of the R program, and then gene set enrichment analysis was carried out. Subsequently, the DEGs were combined with the major module genes chosen using the weighted gene co-expression network. The hub genes were identified by the use of three machine-learning algorithms: random forest, support vector machine-recursive feature elimination, and least absolute shrinkage and selection operator. The receiver operating characteristic curve and nomogram model were used to verify the discrimination and efficacy of the hub genes. In addition, the inflammatory and immune status of pediatric sepsis was assessed using cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT). The relationship between the diagnostic markers and infiltrating immune cells was further studied. RESULTS: Overall, after overlapping key module genes and DEGs, we detected 402 overlapping genes. As pediatric sepsis diagnostic indicators, CYSTM1 (AUC = 0.988), MMP8 (AUC = 0.973), and CD177 (AUC = 0.986) were investigated and demonstrated statistically significant differences (P < 0.05) and diagnostic efficacy in the validation set. As indicated by the immune cell infiltration analysis, multiple immune cells may be involved in the development of pediatric sepsis. Additionally, all diagnostic characteristics may correlate with immune cells to varying degrees. CONCLUSIONS: The candidate hub genes (CD177, CYSTM1, and MMP8) were identified, and the nomogram was constructed for pediatric sepsis diagnosis. Our study could provide potential peripheral blood diagnostic candidate genes for pediatric sepsis patients.

Eukaryotic initiation factor 5A2 mediates hypoxia-induced autophagy and cisplatin resistance.

Hypoxia-induced cisplatin resistance is a major challenge during non-small cell lung cancer (NSCLC) treatment. Based on previous studies, we further explored the effect of eukaryotic initiation factor 5A2 (eIF5A2) in hypoxia-induced cisplatin resistance. In this study, we found that autophagy and cisplatin resistance were increased under hypoxic conditions in three different NSCLC cell lines. Compared with that under normoxic conditions, dramatic upregulation of eIF5A2 and hypoxia inducible factor 1 subunit alpha (HIF-1α) levels were detected under hypoxia exposure. Small interfering RNA silencing of HIF-1α resulted in decreased expression of eIF5A2, indicating that eIF5A2 acts downstream of HIF-1α. In addition, the expression of eIF5A2 was significantly higher in NSCLC tumors compared with that in normal tissues. RNA silencing-mediated downregulation of eIF5A2 decreased hypoxia-induced autophagy, thereby reducing hypoxia-induced cisplatin resistance in NSCLC cells. The roles of eIF5A2 in cisplatin resistance were further validated in vivo. Combined treatment using eIF5A2-targeted downregulation together with cisplatin significantly inhibited tumor growth compared with cisplatin alone in the subcutaneous mouse model. In conclusions, eIF5A2 overexpression is involved in hypoxia-induced autophagy during cisplatin resistance. We suggest that a combination of eIF5A2 targeted therapy and cisplatin chemotherapy is probably an effective strategy to reverse hypoxia-induced cisplatin resistance and inhibit NSCLC development.

Effect and Safety of ALA-PDT Combined with 1550 nm Fractional Therapy Laser in Treating Rosacea.

Objective: To explore the clinical effect and safety of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) combined with 1550 nm fractional laser therapy in the treatment of rosacea. Methods: 114 patients with type I and type II rosacea treated in our hospital from March 2018 to April 2020 were recruited. They were randomly assigned (1 : 1 : 1) to receive ALA-PDT (photodynamic group), 1550 nm fractional laser (laser group), or ALA-PDT and 1550 nm fractional laser therapy (combination group). Outcome measures included skin lesion scores, efficacy, and adverse reactions. Results: After treatment, patients in the three groups showed lower skin lesion scores than before treatment, and the combination group showed significantly lower results than the other groups (P < 0.05). There was no significant difference in the total efficacy among the three groups (P > 0.05), but the combination group outperformed the other groups in the comparison of the efficacy levels (P < 0.05). Edema with lupus erythematosus, pain, and burning sensation was found in some cases but disappeared within 2 to 4 days after symptomatic treatment without interference with subsequent treatment. No patients had pigmentation, hypopigmentation, scars, or other serious adverse reactions. Conclusion: In the treatment of rosacea, ALA-PDT combined with a 1550 nm fractional laser can reduce redness and facilitate skin remodeling, with high efficacy and safety, so it is worthy of clinical promotion and application.

Clinical characteristics and prognosis of 196 Chinese patients with colon cancer.

Aims: To analyze the clinical characteristics and prognostic factors of Chinese patients with colon cancer. Methods: A retrospective analysis of the records of patients with colon cancer underwent surgery between 2014 and 2017 was performed. Univariate analysis in combination with Cox proportional hazard regression model was used to analyze the survival data, so as to reveal the prognostic factors of colon cancer. Data record was based on a standard data form. SPSS version 26.0 was used for data analysis (SPSS, Chicago, IL, United States). Results: The 3-year survival rate and the 5-year survival rate was 79.3% and 68.2%, respectively. Univariate analysis showed that radical surgery, laparoscopic surgery, ascites, swollen lymph nodes at the root of the mesentery, liver metastases, nerve invasion, vascular invasion, tumor node metastasis (TNM) staging, positive level of carbohydrate antigen (CA) 19-9, CA125, CA72-4 and combined detection were positive factors in the prognosis of colon cancer (P < 0.05). Multivariate analysis showed that radical surgery and TNM staging were independent factors affecting the prognosis of patients with colon cancer (P < 0.05). Conclusion: Radical surgery and TNM staging have a significant impact on the prognosis of patients with colon cancer.

Prevalence of mental health problems in Chinese schoolchildren: The influence of measuring impact score and combining information from multiple informants.

BACKGROUND: To measure the effects of using different combinations of multiple informants and the impact score on the estimated prevalence of mental health problems in Chinese schoolchildren. METHODS: Complete information on the Strengths and Difficulties Questionnaire (SDQ) were obtained from students (S), parents (P), and teachers (T) for 4986 schoolchildren (11-17 years-old). We used 3 criteria to determine the prevalence of mental health problems: SDQ cut-off value (previously established in the United Kingdom), SDQ cut-off value plus an impact score of 1 or more, or plus an impact score of 2 or more. A student was defined as having a mental health problem if any informant (S, P, or T) classified the child as 'abnormal'. We compared the prevalence of mental health problems determined from 1 informant, 2 informants, and 3 informants. RESULTS: The prevalence of overall mental health problems increased with rising number of informants, but decreased with increasing impact score. When the impact score was not considered, the prevalence was 8.2% to 14.2% when rated by 1 informant, 18.8% to 24.7% when rated by 2 informants, and 28.3% when rated by all 3 informants. Failure to measure the impact score led to a two to threefold greater estimate of the prevalence of mental health problems. CONCLUSIONS: The types, number, and combinations of multiple informants and use of the impact score must be considered when comparing the results of different studies. It is preferable to use multiple informants and have the impact score taken the impact into account to reflect the real burden of mental health burden in children and adolescent.

First Report of Alternaria alternata causing fruit Rot on Tetradium ruticarpum in China.

Tetradium ruticarpum, previously and commonly known as Evodia rutaecarpa, is a tree that produces a fruit which is one of the most important traditional Chinese medicine herbs in China (Zhao et al. 2015). In July 2019, an investigation of diseases of T. ruticarpum was conducted in the farmland of Ruichang County (29.68° N, 115.65° E), Jiujiang City, China. An unknown fruit rot disease was observed and the incidence rate was estimated to be 60% to 70% within a 5,000 m2 area. The early symptoms appeared as small circular to irregular dark brown or black spots on the fruit, which gradually coalesced to a light brown-to-black discoloration and caused fruit rot. To identify the causal agent of the disease, 10 diseased fruits were collected and surface disinfected with 2% sodium hypochlorite for 2 min, 70% ethanol for 30 s, rinsed in sterile water and dried on filter paper. Tissues from non-symptomatic tissue as well as from the margin between healthy and affected edge were incubated on potato dextrose agar (PDA) at 25±1°C (12 h light/dark) with 90% relative humidity for 5 days. The colonies were brown to black with abundant whitish margins. Conidiophores were brown and measured 20.40 - 43.10×1.30 - 4.20 µm (25.47 × 2.35 µm on average, n=50). Conidia produced in single or branched chains, were obclavate or ovoid, approximately 9.90 - 32.80×6.50 - 14.50 µm (28.75×12.57 µm on average, n=50) with 2 to 5 transverse septa and 0 to 3 longitudinal septa. The colonies were consistent with Alternaria alternata (Simmons 2007). For molecular identification, the f partial internal transcribed spacer (ITS) regions, Glyceraldehyde-3-phosphate dehydrogenase (gapdh) genes, translation elongation factor 1-alpha (TEF) and Alternaria major allergen (Alt a1) gene of the isolate were amplified using primers ITS1/ITS4 (White et al. 1990), GDF/GDR (Templeton et al. 1992), EF1-728F/EF1-986R (Carbone and Kohn 1999) and Alt-for/Alt-rev (Hong et al. 2005). Sequence data showed 100% homology to A. alternata (GenBank accessions No.MN625176.1 (570/570 bp), MK683866.1 (618/618 bp), MK637432.1 (281/281 bp), KT315515.1 (488/488 bp)), respectively and the sequence data were deposited into GenBank with accession numbers MN897753 (ITS), MT041998 (gapdh), MT041999 (TEF), and MT042000 (Alt a1). Based on both morphological and molecular characteristics, the pathogen was identified as A. alternata. To confirm pathogenicity, 10 µl of a spore suspension (1.0 × 106 conidia/ml) obtained from 5-day-old PDA cultures of the strain were inoculated on 20 wounded (using sterile needle) and 20 nonwounded healthy T. ruticarpum fruits previously disinfected in 75% ethanol. Control fruits including 20 wounded fruits and 20 nonwounded fruits were inoculated with sterilized water. All fruits were incubated at 25±1°C (12 h light/dark) with 90% relative humidity. Four days later, all the wounded and non-wounded fruits showed the initial symptoms of black rot which was similar to that observed in the field, while the wounded and nonwounded fruits treated with sterile water remained healthy. The same pathogen was again isolated from the inoculated fruits. The pathogenicity experiment was repeated three times with the same results. As far as we know, this is the first report of A. alternata causing fruits rot on T. ruticarpum in China, and the identification of the pathogen will provide useful information for developing effective control strategies.

Resemblance and clustering of mother's and father's psychopathology levels among Chinese parents of schoolchildren with psychiatric disorders.

BACKGROUND: Few studies have assessed the characteristics of spousal psychopathologies among parents of schoolchildren with and without psychological disorders (PD) in China. METHODS: Parental symptoms were measured using the General Health Questionnaire (GHQ) in 275 mothers and 278 fathers of 298 schoolchildren with PDs diagnosed in a population survey and in 825 mothers and 834 fathers of 894 schoolchildren without PDs as a 1:3 matched comparison group. Spousal GHQ scores were compared. Childhood PD type, presence of childhood comorbidities, and multiple parental and family characteristics were examined as predictors for parental GHQ scores by multiple linear regression analyses. RESULTS: The GHQ scores were significantly higher among mothers and fathers of children with any PD. Maternal GHQ scores were higher than paternal scores and significantly correlated with paternal GHQ scores in both groups. Spousal GHQ, personal PD history, and childhood PD comorbidity were significant independent predictors of both parents' GHQ scores. There were also significant associations among parental chronic disease, low family income, and paternal and maternal GHQ score, as well as among low maternal education, less common disorder (LCD) prevalence in children and maternal GHQ score. The rate of GHQ score ≥3 for both parents was significantly higher in the study group than the control group (15.1 vs.7.0%). CONCLUSIONS: Parents of children with any PD type demonstrate significantly elevated psychopathologies, and psychopathology tends to occur concomitantly and resemble that of the other spouse. Screening and treatment of parental psychiatric symptoms will benefit all family members.

LncRNA Hoxaas3 promotes lung fibroblast activation and fibrosis by targeting miR-450b-5p to regulate Runx1.

Long noncoding RNAs (lncRNAs) participate in organ fibrosis and various pulmonary diseases, but its role in idiopathic pulmonary fibrosis (IPF) is not fully understood. In this study, we found lncRNA Hoxaas3 (Hoxaas3) was up-regulated in the mice model of BLM-induced PF and TGF-ß1-induced fibrogenesis in lung fibroblasts (LF). Overexpression of Hoxaas3 promoted fibrogenesis, whereas Hoxaas3 inhibition attenuated lung fibrosis both in vitro and in vivo, through regulation of miR-450b-5p. Furthermore, miR-450b-5p inhibition stimulated fibrogenesis by regulating runt-related transcription factor 1 (Runx1), whereas up-regulation of miR-450b-5p alleviated fibrogenesis in LF. Mechanistically, our study showed that Hoxaas3 regulated lung fibroblast activation and fibrogenesis by acting as a competing endogenous RNA for miR-450b-5p: Hoxaas3 decreased the expression of miR-450b-5p to stimulate level and activity of Runx1 and induced fibrotic LF, whereas Runx1 inhibition alleviated the pro-fibrotic effect of Hoxaas3. In addition, Hoxaas3 was regulated by TGF-ß1/Smad4 pathway as its transcriptional target. In conclusion, our study showed the role and mechanism of the TGF-ß1/Smad4- Hoxaas3-miR-450b-5p-Runx1 axis for a better understanding of PF, demonstrated Hoxaas3 maybe a new diagnostic biomarker or potential therapeutic target for IPF.

Astragalus polysaccharides attenuate pulmonary fibrosis by inhibiting the epithelial-mesenchymal transition and NF-κB pathway activation.

Astragalus polysaccharides (APS), the active ingredients isolated from the plant Astragalus, have been reported to have numerous biological activities, including anti­inflammatory and antitumor activities. However, the effect of APS on pulmonary fibrosis (PF) remains unknown. The present study aimed to evaluate the protective effect of APS against PF and to explore its underlying mechanisms by using in vivo and in vitro models. A mouse in vivo model of bleomycin­induced PF and an in vitro model of transforming growth factor ß1 (TGF­ß1)­stimulated human lung epithelial A549 cells were established. Histopathologic examination and collagen deposition were investigated by hematoxylin and eosin staining and Masson staining, and by detecting the hydroxyproline content. The expression of related genes was analyzed by western blotting, reverse transcription­quantitative (RT­q) PCR, immunofluorescence and immunohistochemistry. The results from the in vivo mouse model demonstrated that treatment with APS could ameliorate collagen deposition and reduce fibrotic area and hydroxyproline content in the matrix. Furthermore, APS significantly inhibited the epithelial­mesenchymal transition (EMT), as evidenced by an increased level of E­cadherin and a decreased expression of vimentin and alpha smooth muscle actin. Furthermore, APS treatment significantly decreased TGF­ß1­induced EMT and NF­κB pathway activation in vitro. The results from the present study provided new insights on PF regression via the anti­fibrotic effects of APS.

LncRNA HOXA-AS3 confers cisplatin resistance by interacting with HOXA3 in non-small-cell lung carcinoma cells.

Many studies have indicated that the aberrant expression of long noncoding RNAs (lncRNAs) is responsible for drug resistance, which represents a substantial obstacle for cancer therapy. In the present study, we aimed to investigate the role of the lncRNA HOXA-AS3 in drug resistance and elucidate its underlying mechanisms in non-small-cell lung carcinoma (NSCLC) cells. The role of HOXA-AS3 in drug resistance was demonstrated by the cell counting kit-8 assay (CCK-8), ethynyldeoxyuridine (EDU) assay, and flow cytometry analysis. Tumor xenografts in nude mice were established to evaluate the antitumor effects of HOXA-AS3 knockdown in vivo. Western blotting and quantitative real-time PCR were used to evaluate protein and RNA expression. RNA pull-down assays, mass spectrometry, and RNA immunoprecipitation were performed to confirm the molecular mechanism of HOXA-AS3 in the cisplatin resistance of NSCLC cells. We found that HOXA-AS3 levels increased with cisplatin treatment and knockdown of HOXA-AS3 enhance the efficacy of cisplatin in vitro and in vivo. Mechanistic investigations showed that HOXA-AS3 conferred cisplatin resistance by down-regulating homeobox A3 (HOXA3) expression. Moreover, HOXA-AS3 was demonstrated to interact with both the mRNA and protein forms of HOXA3. In addition, HOXA3 knockdown increased cisplatin resistance and induced epithelial-mesenchymal transition (EMT). Taken together, our findings suggested that additional research into HOXA-AS3 might provide a better understanding of the mechanisms of drug resistance and promote the development of a novel and efficient strategy to treat NSCLC.

Meta-Analysis of Astragalus-Containing Traditional Chinese Medicine Combined With Chemotherapy for Colorectal Cancer: Efficacy and Safety to Tumor Response.

This meta analysis evaluated the comparative safety and efficacy for the addition of Astragalus-based Chinese medicines combined with chemotherapy and chemotherapy alone for colorectal cancer (CRC) treatment. Systematic literature search was performed by PubMed, EMBSAE, Ovid, Web of Science, Cochrane Library, Chinese Science and Technology Journals (CQVIP), China Academic Journals (CNKI), and Chinese Biomedical Literature database. A total of 22 studies which reported on 1,409 subjects were identified. This meta-analysis indicated that the combination of Astragalus-based Chinese medicines and chemotherapy may increase the efficiency of tumor response rate (TRR) for the treatment of CRC patients (RR: 1.52; 95% CI: 1.24-1.87; p < 0.0001), improve their life quality based on KPS (RR: 2.51; 95% CI: 1.85-3.42; p < 0.00001 and WMD: 10.96; 95% CI: 9.45-12.47; p < 0.00001), and reduce the adverse reactions, including neutropenia (RR: 0.52; 95% CI: 0.44-0.62; p < 0.00001), anemia (RR: 0.49; 95% CI: 0.34-0.70; p < 0.0001), thrombocytopenia (RR: 0.59; 95% CI: 0.46-0.77; p = 0.0001), nausea and vomiting (RR: 0.56; 95% CI: 0.46-0.68; p < 0.00001), diarrhea (RR: 0.55; 95% CI: 0.40-0.75; p = 0.0001), and neurotoxicity (RR: 0.56; 95% CI: 0.49-0.65; p < 0.00001). Hepatic dysfunction (RR: 0.76; 95% CI: 0.53-1.09; p = 0.13) and renal dysfunction (RR: 0.95; 95% CI: 0.51-1.76; p = 0.87) were similar between two groups. The results showed that Astragalus-based Chinese medicines combined with chemotherapy in the treatment of CRC may increase the efficiency of TRR, reduce chemotherapeutic agents-associated adverse reactions, and improve their life quality when compared with chemotherapy alone, but further randomized studies are warranted.

Upregulated circular RNA circ_0070934 facilitates cutaneous squamous cell carcinoma cell growth and invasion by sponging miR-1238 and miR-1247-5p.

Accumulating studies have appreciated circular RNAs (circRNAs) as novel prognostic biomarkers and therapeutic targets in malignant carcinomas. Here, we aim to investigate the expression of a novel circRNA, circ_0070934. The biological roles and mechanisms of circ_0070934 in cutaneous squamous cell carcinoma (CSCC) were explored. The expression of circ_0070934 in CSCC tissues and cell lines was evaluated by qRT-PCR. Loss-of-function and gain-of-function assays were performed to detect cell proliferation, apoptosis, migration and invasion in vitro. Moreover, the underlying molecular mechanism of circ_0070934 was predicted by online database and luciferase reporter assay. Abnormally overexpression of circ_0070934 was detected in CSCC samples and cell lines. Inhibition of cell proliferation, invasion, migration, and increased apoptosis were observed upon circ_0070934 knockdown. The opposite effect was observed in the circ_0070934 overexpression cells. Circ_0070934 expression was negatively correlated with miR-1238 and miR-1247-5p expression in CSCC and luciferase reporter experiment verified the binding ability between circ_0070934 and miR-1238/miR-1247-5p. Rescue experiments further identified that the oncogenic role of circ_0070934 is attributed to its suppression of miR-1238 and miR-1247-5p. Taken together, our results implicate that circ_0070934 is correlated with tumor aggressiveness by serving as an oncogenic circRNA in CSCC.

High energy closed-loop cycle narrow linewidth optically pumped XeF(C-A) blue laser at a repetition rate of 10 Hz.

We report for the first time on a closed-loop cycle narrow linewidth XeF(C-A) blue laser at a repetition rate of up to 10 Hz with each pulse energy of >1 J. A FWHM linewidth of less than 1.5 nm (minimum to 1.1 nm) with a highly stable wavelength centered at 488.3 nm was achieved by employing a polarization-independent custom-designed narrowband optical filter (NBOF) into the cavity. The pulse energy, as well as the repetition rate, to the best of our knowledge, is the highest ever reported in the narrow linewidth XeF(C-A) blue lasers at repetitively-pulsed mode.

TREM2 inhibits inflammatory responses in mouse microglia by suppressing the PI3K/NF-κB signaling.

This study aimed to investigate the effects of triggering receptor expressed on myeloid cell-2 (TREM2) on the production of pro-inflammatory mediators and cytokines induced by lipopolysaccharide (LPS) in BV2 microglia. TREM2 expression or TREM2-specific siRNA were used to induce TREM2 overexpression or silencing. The BV2 cells were pre-treated with the PI3 K inhibitor of LY294002 for 1 h and stimulated with LPS for 24 h. Then, the cell viability, apoptosis, phagocytosis, nitric oxide (NO), lactate dehydrogenase (LDH), and cytokine production, as well as the activation of AKT and NF-kB were determined, respectively. We found LPS stimulation significantly reduced BV2 cell viability, enhanced BV2 cell phagocytosis and apoptosis compared to the control groups. In addition, LPS stimulation significantly increased the production of NO, LDH, TNF-α, IL-1ß, and the activation of AKT and NF-kB, while decreased the levels of IL-10 and TGF-ß1. However, these pro-inflammatory effects were significantly attenuated by TREM2 overexpression or pre-treatment with LY294002, while enhanced by TREM2 silencing. Thus, we concluded that TREM2 inhibited neuroinflammation by down-regulating PI3 K/AKT and NF-kB signaling in BV2 microglia. Above all, therapeutic enhanced TREM2 expression may be a new strategy for intervention of neuroinflammatory diseases.

Evaluation of inhaled recombinant human insulin dry powders: pharmacokinetics, pharmacodynamics and 14-day inhalation.

OBJECTIVES: The present study was designed to assess the pharmacokinetic and pharmacodynamic performance of inhaled recombinant human insulin (rh-insulin) dry powders together with their safety profiles after 14-day inhalation. METHODS: In the pharmacokinetic and pharmacodynamic study, pulmonary surfactant (PS)-loaded and phospholipid hexadecanol tyloxapol (PHT)-loaded rh-insulin dry powders were intratracheally administered to male rats at the dose of 20 U/kg. Novolin R was used as control. Serum glucose and rh-insulin concentrations were determined by glucose oxidase method and human rh-insulin CLIA kit, respectively. For the safety study, rats were exposed to rh-insulin dry powders or air for 14-day by nose-only inhalation chambers. Bronchoalveolar lavage and histopathology examinations were performed after inhalation. KEY FINDINGS: There were no significant differences in the major pharmacokinetic and pharmacodynamic parameters between PS-loaded and PHT-loaded rh-insulin dry powders. The relative bioavailabilities and pharmacodynamic availabilities were 39.9%, 25.6% for PS-loaded dry powders and 30.1%, 23% for PHT-loaded dry powders, respectively. Total protein was the only injury marker that was significantly altered. Histopathology examinations showed the ranking of irritations (from slight to severe) were PHT-loaded rh-insulin, negative air control and PS-loaded rh-insulin. CONCLUSIONS: Both PS- and PHT-loaded rh-insulin dry powders were able to deliver rh-insulin systemically with appropriate pharmacokinetic, pharmacodynamic and safety profiles.

Association of recent gay-related stressful events with depressive symptoms in Chinese men who have sex with men.

BACKGROUND: To assess the association of different gay-related stressful events (GRSEs) with depressive symptoms in Chinese men who have sex with men (MSM). METHOD: A total of 807 MSM were recruited using respondent-driven sampling from four cities in northeastern China. GRSEs were measured using the Gay Related Stressful Life Events Scale, and depressive symptoms were assessed using the Self-Rating Depression Scale (SDS). RESULTS: A total of 26.0% of study participants experienced GRSEs in the past three months, and the average SDS score was lower than the previously reported national average for China. The study participants had significantly elevated risks of depression (SDS score ≥ 53) due to recent troubles with a boss (OR = 4.92, 95% CI = 1.87-12.97) or a workmate (OR = 3.68, 95% CI = 1.52-8.88), loss of a close friend (OR = 2.41, 95% CI = 1.39-4.18), argument with a close friend (OR = 2.07, 95% CI = 1.33-3.22), and being physically assaulted (OR = 2.08, 95% CI = 0.98-4.43). Arguments with family members or classmates had no significant effect on depression. Multiple logistic regression analysis showed that the number of GRSEs, a lower level of education, more advanced age, and HIV infection significantly increased the risk of depression. CONCLUSIONS: There are large differences in the associations of different types of GRSEs with depressive symptoms. Reducing the stigmatization and discrimination toward MSM in all social environments and improving the capability of MSM to cope with different types of GRSEs may improve their emotional wellbeing.

MicroRNA-331 Inhibits Proliferation and Invasion of Melanoma Cells by Targeting Astrocyte-Elevated Gene-1.

Melanoma is characterized by aggressive invasion, early metastasis, and resistance to existing chemotherapeutic agents. Accumulated studies have reported that microRNA (miRNA) is a potentially robust molecular tool for developing future therapeutic technologies. Therefore, examining the expression patterns, biological roles, and associated mechanisms of cancer-related miRNAs in melanoma is essential for developing novel therapeutic targets for patients with this disease. In this study, miRNA-331 (miR-331) was underexpressed in melanoma tissues and cell lines. Functional assays revealed that the enforced expression of miR-331 inhibited cell proliferation and invasion. In addition, astrocyte-elevated gene-1 (AEG-1) was identified as a novel target of miR-331 through bioinformatics analysis, reverse transcription quantitative polymerase chain reaction analysis, Western blot analysis, dual-luciferase reporter assay, and Spearman's correlation analysis. Furthermore, reintroduction of AEG-1 partially abrogated the inhibitory effects of miR-331 overexpression on the proliferation and invasion of melanoma cells. Moreover, miR-331 suppressed the activation of the PTEN/AKT signaling pathway in melanoma by inhibiting AEG-1. In short, miR-331 may play tumor-suppressive roles in melanoma by directly targeting AEG-1 and regulating the PTEN/AKT signaling pathway, suggesting that miR-331 could be investigated as a therapeutic strategy for patients with this malignancy.

Association of recent gay-related stressful events and emotional distress with suicidal behaviors over 12 months in Chinese men who have sex with men.

INTRODUCTION: The study was designed to assess the association of gay-related stressful events (GRSEs) and emotional distress with suicidal behaviors over a 12-month period in Chinese men who have sex with men (MSM). METHODS: A total of 807 MSM were recruited using a respondent-driven sampling method from 4 cities in northeastern China. The GRSEs were measured using the Gay-related Stressful Life Events Scale, depression using the Self-rating Depression Scale, and anxiety using the Self-rating Anxiety Scale. RESULTS: A total of 26.0% of study participants experienced GRSEs during the 3 months, and their average Self-rating Depression Scale and Self-rating Anxiety Scale scores were significantly lower than the national norms. Over a 12-month period, the prevalence of suicidal ideation, plan, and attempt was 9.7%, 4.0%, and 3.0%, respectively, each of which is at least 3 to 4 times greater than that of male adults in the general population of China. Multiple logistic regression analysis showed that GRSEs significantly increased the risk of suicidal ideation (odds ratio [OR] = 2.3, 95% confidence interval [CI], 1.4-3.7) and plan (OR = 2.8, 95% CI, 1.3-6.0). Depressive symptoms significantly increased the risk of suicidal ideation (OR = 3.5, 95% CI, 2.1-5.8), plan (OR = 4.4, 95% CI, 2.0-9.6), and attempt (OR = 5.6, 95% CI, 21.94.8). Anxiety symptoms (OR = 3.4, 95% CI, 1.4-8.4) and cohabitation with a same sex partner (OR = 3.0, 95% CI, 1.2-7.9) significantly increased the risk of suicide attempt. DISCUSSION: More efforts to reduce GRSE are worth investigating as a strategy to reduce suicidal thoughts and behaviors in Chinese MSM.

Pretreatment with Oxycodone Simultaneously Reduces Etomidate-Induced Myoclonus and Rocuronium-Induced Withdrawal Movements During Rapid-Sequence Induction.

BACKGROUND Etomidate and rocuronium are often paired in rapid-sequence anesthesia induction. However, the effect of pretreatment with oxycodone on myoclonic and withdrawal movements has not been previously investigated. The aim of this study was to evaluate the effects of oxycodone on the incidence and severity of etomidate-induced myoclonus and rocuronium-induced nociceptive withdrawal movements during rapid-sequence anesthesia induction. MATERIAL AND METHODS We randomly divided 120 patients into the saline group (group S) and the oxycodone group (group O) (n=60 in each group). Patients received 0.05 mg/kg oxycodone or saline intravenously 2 min before administration of 0.3 mg/kg etomidate. The occurrence and severity of myoclonus were assessed after administration of etomidate, then rocuronium was injected, followed by evaluation of withdrawal movements. RESULTS The total frequency of involuntary movements following sequential administration of etomidate and rocuronium was significantly lower in Group O than in Group S (28.3% vs. 90%, p<0.001). The total frequency and grade 3 severity of myoclonus following etomidate injection in Group O was significantly lower than in Group S (25.0% vs. 63.3% for total frequency; 0 vs. 10 for grade 3 severity, P<0.001). The total frequency and grade 3 intensity of withdrawal movements were significantly less in Group O than in Group S (6.7% vs. 73.3% for total frequency; 0 vs. 11 for grade 3 intensity, P<0.001). CONCLUSIONS Oxycodone is effective for simultaneously preventing etomidate-induced myoclonus and rocuronium-induced withdrawal movements during general anesthesia induction.