Influence of meteorological factors on open biomass burning at a background site in Northeast China.

Biomass burning (BB) is a very important emission source that significantly adversely impacts regional air quality. BB produces a large number of primary organic aerosol (POA) and black carbon (BC). Besides, BB also provides many precursors for secondary organic aerosol (SOA) generation. In this work, the ratio of levoglucosan (LG) to organic carbon (OC) and the fire hotspots map was used to identify the open biomass burning (OBB) events, which occurred in two representative episodes, October 13 to November 30, 2020, and April 1 to April 30, 2021. The ratio of organic aerosol (OA) to reconstructed PM2.5 concentration (PM2.5*) increased with the increase of LG/OC. When LG/OC ratio is higher than 0.03, the highest OA/PM2.5* ratio can reach 80%, which means the contribution of OBB to OA is crucial. According to the ratio of LG to K+, LG to mannosan (MN) and the regional characteristics of Longfengshan, it can be determined that the crop residuals are the main fuel. The occurrence of OBB coincides with farmers' preferred choices, i.e., burning biomass in "bright weather". The "bright weather" refers to the meteorological conditions with high temperature, low humidity, and without rain. Meteorological factors indirectly affect regional biomass combustion pollution by influencing farmers' active choices.

Tailoring the Growth and Morphology of Lithium Peroxide: Nickel Sulfide/Nickel Phosphate Nanotubes with Optimized Electronic Structure for Lithium-Oxygen Batteries.

Heterogeneous crystalline-amorphous structures, with tunable electronic structures and morphology, hold immense promise as catalysts for lithium-oxygen batteries (LOBs). Herein, a nanotube network constructed by crystalline nickel sulfide/amorphous nickel phosphate (NiS/NiPO) heterostructure is prepared on Ni foam through the sulfurization of the precursor generated hydrothermally. Used as cathodes, the NiS/NiPO nanotubes with optimized electronic structure can induce the deposition of the highly porous and interconnected structure of Li2 O2 with rich Li2 O2 -electrolyte interfaces. Abundant active sites can be created on NiS/NiPO through the charge redistribution for the uniform nucleation and growth of Li2 O2 . Moreover, nanotube networks endow cathodes with efficient transport channels and sufficient space for the accommodation of Li2 O2 . A high discharge capacity of 27 003.6 mAh g-1 and a low charge overpotential of 0.58 V at 1000 mAh g-1 can be achieved at 200 mA g-1 . This work provides valuable insight into the unique role of the electronic structure and morphology of catalysts in the formation mechanisms of Li2 O2 and the performances of LOBs.

Effects of Using Different Indirect Techniques on the Calculation of Reference Intervals: Observational Study.

BACKGROUND: Reference intervals (RIs) play an important role in clinical decision-making. However, due to the time, labor, and financial costs involved in establishing RIs using direct means, the use of indirect methods, based on big data previously obtained from clinical laboratories, is getting increasing attention. Different indirect techniques combined with different data transformation methods and outlier removal might cause differences in the calculation of RIs. However, there are few systematic evaluations of this. OBJECTIVE: This study used data derived from direct methods as reference standards and evaluated the accuracy of combinations of different data transformation, outlier removal, and indirect techniques in establishing complete blood count (CBC) RIs for large-scale data. METHODS: The CBC data of populations aged ≥18 years undergoing physical examination from January 2010 to December 2011 were retrieved from the First Affiliated Hospital of China Medical University in northern China. After exclusion of repeated individuals, we performed parametric, nonparametric, Hoffmann, Bhattacharya, and truncation points and Kolmogorov-Smirnov distance (kosmic) indirect methods, combined with log or BoxCox transformation, and Reed-Dixon, Tukey, and iterative mean (3SD) outlier removal methods in order to derive the RIs of 8 CBC parameters and compared the results with those directly and previously established. Furthermore, bias ratios (BRs) were calculated to assess which combination of indirect technique, data transformation pattern, and outlier removal method is preferrable. RESULTS: Raw data showed that the degrees of skewness of the white blood cell (WBC) count, platelet (PLT) count, mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and mean corpuscular volume (MCV) were much more obvious than those of other CBC parameters. After log or BoxCox transformation combined with Tukey or iterative mean (3SD) processing, the distribution types of these data were close to Gaussian distribution. Tukey-based outlier removal yielded the maximum number of outliers. The lower-limit bias of WBC (male), PLT (male), hemoglobin (HGB; male), MCH (male/female), and MCV (female) was greater than that of the corresponding upper limit for more than half of 30 indirect methods. Computational indirect choices of CBC parameters for males and females were inconsistent. The RIs of MCHC established by the direct method for females were narrow. For this, the kosmic method was markedly superior, which contrasted with the RI calculation of CBC parameters with high |BR| qualification rates for males. Among the top 10 methodologies for the WBC count, PLT count, HGB, MCV, and MCHC with a high-BR qualification rate among males, the Bhattacharya, Hoffmann, and parametric methods were superior to the other 2 indirect methods. CONCLUSIONS: Compared to results derived by the direct method, outlier removal methods and indirect techniques markedly influence the final RIs, whereas data transformation has negligible effects, except for obviously skewed data. Specifically, the outlier removal efficiency of Tukey and iterative mean (3SD) methods is almost equivalent. Furthermore, the choice of indirect techniques depends more on the characteristics of the studied analyte itself. This study provides scientific evidence for clinical laboratories to use their previous data sets to establish RIs.

Glycosylation Contributes to Thermostability and Proteolytic Resistance of rFIP-nha (Nectria haematococca).

Glycosylation is an important post-translational modification of proteins, contributing to protein function, stability and subcellular localization. Fungal immunomodulatory proteins (FIPs) are a group of small proteins with notable immunomodulatory activity, some of which are glycoproteins. In this study, the impact of glycosylation on the bioactivity and biochemical characteristics of FIP-nha (from Nectria haematococca) is described. Three rFIP-nha glycan mutants (N5A, N39A, N5+39A) were constructed and expressed in Pichia pastoris to study the functionality of the specific N-glycosylation on amino acid N5 and N39. Their protein characteristics, structure, stability and activity were tested. WT and mutants all formed tetramers, with no obvious difference in crystal structures. Their melting temperatures were 82.2 °C (WT), 81.4 °C (N5A), 80.7 °C (N39A) and 80.1 °C (N5+39A), indicating that glycosylation improves thermostability of rFIP-nha. Digestion assays showed that glycosylation on either site improved pepsin resistance, while 39N-glycosylation was important for trypsin resistance. Based on the 3D structure and analysis of enzyme cleavage sites, we conclude that glycosylation might interfere with hydrolysis via increasing steric hindrance. WT and mutants exerted similar bioactivity on tumor cell metabolism and red blood cells hemagglutination. Taken together, these findings indicate that glycosylation of FIP-nha impacts its thermostability and digestion resistance.

[Saikosaponin D regulates apoptosis and autophagy of pancreatic cancer Panc-1 cells via Akt/mTOR pathway].

This study aims to investigate the effect and mechanism of saikosaponin D on the proliferation, apoptosis, and autophagy of pancreatic cancer Panc-1 cells. The cell counting kit(CCK-8) was used to examine the effects of 7, 10, 13, 16, 19, 22, 25, and 28 µmol·L~(-1) saikosaponin D on the proliferation of Panc-1 cells. Three groups including the control(0 µmol·L~(-1)), low-concentration(10 µmol·L~(-1)) saikosaponin D, and high-concentration(16 µmol·L~(-1)) saikosaponin D groups were designed. The colony formation assay was employed to measure the effect of saikosaponin D on the colony formation rate of Panc-1 cells. The cells treated with saikosaponin D were stained with hematoxylin-eosin(HE), and the changes of cell morphology were observed. Hoechst 33258 fluorescent staining was used to detect the effect of saikosaponin D on the cell apoptosis. The autophagy staining assay kit with MDC was used to examine the effect of saikosaponin D on the autophagy of Panc-1 cells. Western blot and immunocytochemistry(ICC) were employed to examine the effect of saikosaponin D on the expression levels and distribution of B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), cysteine-aspartic acid protease-3(caspase-3), cleaved caspase-3, autophagy-associated protein Beclin1, microtubule-associated protein light chain 3(LC3), protein kinase B(Akt), phosphorylated protein kinase B(p-Akt), mammalian target of rapamycin(mTOR), and phosphorylated mammalian target of rapamycin(p-mTOR). The results showed that compared with the control group, saikosaponin D decreased the proliferation rate of Panc-1 cells in a dose-dependent and time-dependent manner. The colony formation rate of the cells significantly decreased after saikosaponin D treatment. Compared with the control group, the cells treated with saikosaponin D became small, accompanied by the formation of apoptotic bodies. The saikosaponin D groups showed increased apoptosis rate and autophagic vesicle accumulation. Compared with the control group, saikosaponin D up-regulated the expression of Bax, cleaved caspase3, Beclin1, LC3Ⅱ/LC3Ⅰ and down-regulated the expression of Bcl-2, caspase-3, p-Akt/Akt, and p-mTOR/mTOR. In addition, these proteins mainly existed in the cytoplasm. In conclusion, saikosaponin D can inhibit the proliferation and induce the apoptosis and autophagy of Panc-1 cells via inhibiting the Akt/mTOR pathway.

Safety, Tolerability, and Pharmacokinetics of the Novel Hepatitis B Virus Expression Inhibitor GST-HG131 in Healthy Chinese Subjects: a First-in-Human Single- and Multiple-Dose Escalation Trial.

GST-HG131, a novel dihydroquinolizinone (DHQ) compound, has been shown to reduce circulating levels of HBsAg in animals. This first-in-human trial evaluated the safety, tolerability, and pharmacokinetic profile of GST-HG131 in healthy Chinese subjects. This was a double-blind, randomized, placebo-controlled phase Ia clinical trial that was conducted in two parts. Part A was a single-ascending-dose (SAD; GST-HG131 10 30, 60, 100, 150, 200, 250 or 300 mg or placebo) study, which also assessed the food effect of GST-HG131 100 mg. Part B was a multiple-ascending-dose (MAD; GST-HG131 30, 60 or 100 mg or placebo BID) study. Tolerability assessments included adverse events, vital signs, 12-lead electrocardiogram, physical examination, and clinical laboratory tests. PK analyses were conducted in blood, urine, and fecal samples. Single doses of GST-HG131 ≤ 300 mg and multiple doses of GST-HG131 ≤ 60 mg were generally safe and well tolerated; however, multiple dosing was stopped at GST-HG131 100 mg, as pre-defined stopping rules specified in the protocol were met (Grade II drug related AEs of nausea and dizziness in >50% of subjects). In the SAD study, median tmax of GST-HG131 was 1-6 h, and t1/2 ranged from 3.88 h to 14.3 h. PK parameters were proportional to dose. Exposure was reduced after food intake. In the MAD study, steady-state was attained on day 4, and there was no apparent plasma accumulation of GST-HG131 on day 7 (Racc < 1.5). In conclusion, GST-HG131 exhibited an acceptable safety profile in healthy subjects at single doses ranging from 10-300 mg and multiple doses (BID) ranging from 30-60 mg, and the MAD doses (30 mg and 60 mg BID) that potentially meet the therapeutic AUC requirements. These findings imply GST-HG131 has potential as a therapeutic option for CHB infection. (This study has been registered at ClinicalTrials.gov under identifier NCT04499443.).

miR-351-3p promotes rat amniotic fluid-derived mesenchymal stromal cell proliferation via targeting the coding sequence of Abca4.

Amniotic fluid-derived mesenchymal stromal cells (AFMSCs) present different features, depending on the isolation timing and culture conditions. The lack of uniform experimental standards hinders the comparison of results from different studies on AFMSCs. Moreover, understanding the molecular mechanisms that underlie the features of AFMSCs isolated at different embryonic developmental stages might allow the obtention of more viable and highly proliferative AFMSCs through genetic modification. We isolated AFMSCs from pregnant rats at embryonic day (E)12, E15, E18, and E21 and compared their cell proliferation capacity and transcriptome. The cell counting kit-8 assay and RNA sequencing revealed that E12 and E15 AFMSCs showed different characteristics from E18 and E21 AFMSCs. Therefore, AFMSCs were divided into two groups: early (E12 and E15) and late (E18 and E21) pregnancy-stage groups. Next, we screened the gene/microRNA pair Abca4/miR-351-3p that was related to cell proliferation. Abca4 knockdown/overexpression suggested that this gene represses the proliferation of AFMSCs, which is a newly discovered function of this gene. Finally, dual luciferase reporter gene assays confirmed that miR-351-3p targeted the coding sequence of Abca4 and regulated AFMSC proliferation. miR-351-3p promotes AFMSC proliferation via targeting the coding sequence of Abca4. Our findings provide a molecular foundation for further research for obtaining AFMSCs with a higher proliferation capacity.

On the fossil and non-fossil fuel sources of carbonaceous aerosol with radiocarbon and AMS-PMF methods during winter hazy days in a rural area of North China plain.

Regional transport is a key source of carbonaceous aerosol in many Chinese megacities including Beijing. The sources of carbonaceous aerosol in urban areas have been studied extensively but are poorly known in upwind rural areas. This work aims to quantify the contributions of fossil and non-fossil fuel emissions to carbonaceous aerosols at a rural site in North China Plain in winter 2016. We integrated online high resolution-time of flight-aerosol mass spectrometer (HR-TOF-AMS) observations and radiocarbon (14C) measurements of fine particles with Positive Matrix Factorization (PMF) analysis as well as Extended Gelencsér (EG) method. We found that fine particle concentration is much higher at the rural site than in Beijing during the campaign (Dec 7, 2016 to Jan 8, 2017). PMF analysis of the AMS data showed that coal-combustion related organic aerosol (CCOA + Oxidized CCOA) and more oxidized oxygenated organic aerosol (MO-OOA) contributed 48% and 30% of organic matter to non-refractory PM1 (NR-PM1) mass. About 2/3 of the OC and EC were from fossil-fuel combustion. The EG method, combining AMS-PMF and 14C data, showed that primary and secondary OC from fossil fuel contribute 35% and 22% to total carbon (TC), coal combustion emission dominates the fossil fuel sources, and biomass burning accounted for 21% of carbonaceous aerosol. In summary, our results confirm that fossil fuel combustion was the dominant source of carbonaceous aerosol during heavy pollution events in the rural areas. Significant emissions of solid fuel carbonaceous aerosols at rural areas can affect air quality in downwind cities such as Beijing and Tianjin, highlighting the benefits of energy transition from solid fuels to cleaner energy in rural areas.

Efficacy of anti-fungal agents for invasive fungal infection prophylaxis in liver transplant recipients: A network meta-analysis.

At present, there is still a lack of effective invasive fungal prophylaxis therapy in liver transplant recipients (LTRs). This study aimed to analysis the latest evidence on efficacy of current prophylactic anti-fungal therapy, and systematically compare between anti-fungal agents and placebo by a fixed-effects meta-analysis in all randomised controlled trials. A network meta-analysis was performed for invasive fungal infection (IFI) among different agents in 14 randomised controlled trials, in which 10 anti-fungal approaches were identified. Overall, anti-fungal prophylaxis reduced the rate of IFI (RR 0.30, 95% CI 0.18-0.52) and proven IFI (RR 0.27, 95% CI 0.14-0.53) when compared to placebo. In the network meta-analysis, an equivalent reduction in the rate of IFI was observed in fluconazole (OR 4.70, 95% CI 1.22-18.10), itraconazole (OR 5.82, 95% CI 1.10-30.71) and Liposomal amphotericin B (LAmB, OR 5.74, 95% CI 1.29-25.58) groups when compared with placebo. Anidulafungin might be the most effective agents in IFI prevention; however, this superiority did not meet statistically significance. Our study indicated that fluconazole, echinocandins and LAmB are equivalent in efficacy. Of which, fluconazole is recommended for the prevention of IFI in LTRs due to its efficacy, economics and compliance.

Discordance between perceived risk and actual risky sexual behaviors among undergraduate university students in mainland China: a cross-sectional study.

BACKGROUND: HIV prevention, diagnosis, treatment and care services might be hampered by inaccurate risk assessment. This study aimed to investigate the extent of and factors associated with the discordance between perceived risk and actual risky sexual behaviors among undergraduates in mainland China, guided by the Anderson's behavioral model. METHODS: This study involved a secondary analysis of cross-sectional data collected during the fall semester of 2018-2019 academic year. The present analysis was restricted to 8808 undergraduates with low risk perception. Those who had low perceived risk but actually engaged in risky sexual behaviors were categorized as risk discordance (RD). Univariate and multivariate Logistic regression analyses were conducted to identify factors associated with RD. RESULTS: Overall, the discordance rate between perceived and actual risk was 8.5% (95% CI: 7.9%-9.1%). Multivariate Logistic regression analysis indicated that non-heterosexual women (AOR = 0.41, 95% CI:0.27-0.60), heterosexual men (AOR = 0.45, 95% CI:0.33-0.61) and women (AOR = 0.26, 95% CI:0.19-0.35) were less likely to exhibit RD, when compared with non- heterosexual men. Furthermore, non-freshmen (AOR = 1.57, 95% CI:1.30-1.90), early initiators of sexual intercourse (AOR = 5.82, 95% CI:4.10-8.26), and those who had lower levels of HIV knowledge (AOR = 1.28, 95% CI:1.08-1.51), displayed higher levels of stigma against PLHIV (AOR = 1.50, 95% CI:1.26-1.77) and had ever been tested for HIV (AOR = 1.36, 95% CI:1.04-1.77) were more prone to reporting RD. Those with more enabling resources [i.e., displaying high levels of condom use self-efficacy (AOR = 0.70, 95% CI:0.59-0.84) and being knowledge of local testing center (AOR = 0.71, 95% CI:0.60-0.83)] were less likely to report RD. However, spending more than 2000 Yuan a month on basic needs (AOR = 2.55, 95% CI:2.07-3.14), residing in urban areas (AOR = 1.35, 95% CI:1.15-1.59) and being knowledgeable of the national AIDS policy (AOR = 1.40,95% CI:1.18-1.66) increased the chance of exhibiting RD. CONCLUSIONS: Comprehensive interventions, including targeting students with high-risk characteristics, improving the acceptability of PrEP and PEP, conducting health education, enhancing self-efficacy for using condoms and making opt-out HIV testing routine in college campus, should be taken to reduce the discordance between perceived and actual HIV risk and finally to reach the goal of Zero AIDS.

Prevalence of and factors associated with unintended pregnancies among sexually active undergraduates in mainland China.

BACKGROUND: Unintended pregnancies (UIP) among unmarried sexually active college students in mainland China have emerged as a major reproductive health issue with detrimental personal and socioeconomic consequences. This cross-sectional study aimed to determine the prevalence and factors associated with UIP among sexually active undergraduates in mainland China. METHODS: Between September 8, 2019 and January 17, 2020, a total of 48,660 participants were recruited across the Chinese mainland to complete the self-administered, structured, online questionnaire. This analysis was restricted to 6347 sexually experienced, never-married 15-26 year old undergraduates. Pearson's Chi square tests and multivariate Logistic regression analyses were performed to identify sociodemographic, familial and individual variables associated with UIP. RESULTS: The overall prevalence of UIP was 17.7%. More specifically, 19.5% of male college students reported they had unintentionally gotten a partner pregnant, while 14.9% of female college students became unintentionally pregnant. Students who experienced UIP were more likely to belong to the older age group (23-26 years), live with only one parent or live without parents at home, report that their family members approve of premarital sex, initiate sexual activity younger than 14 years old and have casual sex partners. Furthermore, females with multiple partners and males who came from low- income households, experienced sexual abuse, perceived difficulties in acquiring condoms and did not know how to use condoms correctly were also at higher risk of experiencing an unintended pregnancy. CONCLUSION: In order to prevent UIP, a comprehensive intervention measure should be taken to target older students and those engaging in risky sexual behaviors, work with young male students to improve condom use skills, improve the availability of free condoms, optimize the involvement of parents and other family members in their children's sex education.

In this study, we aimed to determine the prevalence and factors associated with UIP among sexually active undergraduates in mainland China. Between September 8, 2019 and January 17, 2020, a total of 48,660 participants were recruited from the Chinese mainland to complete the self-administered, structured, online questionnaire. This analysis was restricted to 6347 sexually experienced, never-married 15­26 year old undergraduates. Based on a social-ecological theoretical framework, we ran separate multivariate Logistic regression models for men and women to identify sociodemographic, familial and individual variables associated with UIP. Our findings indicate that the overall prevalence of UIP was 17.7%. More specifically, 19.5% of male college students reported they had unintentionally gotten a partner pregnant, while 14.9% of female college students became unintentionally pregnant. Students who experienced UIP were more likely to belong to the older age group, live with only one parent or live without parents at home, report that their family members approve of premarital sex, initiate sexual activity younger than 14 years old and have casual sex partners. Furthermore, females with multiple partners and males who came from low-income households, experienced sexual abuse, perceived difficulties in acquiring condoms and did not know how to use condoms correctly were also at higher risk of having an unintended pregnancy. In order to prevent UIP, a comprehensive intervention measure should be taken to target older students and those engaging in risky sexual behaviors, work with young male students to improve condom use skills, improve the availability of free condoms, optimize the involvement of parents and other family members in their children's sex education.

Cytosolic mtDNA released from pneumolysin-damaged mitochondria triggers IFN-ß production in epithelial cells.

Pneumolysin (Ply) is a major virulence factor of Streptococcus pneumoniae. Ply-induced interferon-ß (IFN-ß) expression in host macrophages has been shown to be due to the accumulation of mitochondrial deoxyribonucleic acid (mtDNA) in the cytoplasm during S. pneumoniae infection. Our findings extend this work to show human bronchial epithelial cells that reside at the interface of inflammatory injury, BEAS-2B, adapt to local cues by altering mitochondrial states and releasing excess mtDNA. The results in this research showed that purified Ply induced the expression of IFN-ß in human epithelial cells, which was accompanied by mitochondrial damage both in vivo and in vitro. The observations also were supported by the increased mtDNA concentrations in the bronchial lavage fluid of mice infected with S. pneumoniae. In summary, our study demonstrated that Ply triggered the production of IFN-ß in epithelial cells, and this response was mediated by mtDNA released from Ply-damaged mitochondria. It displayed an impressive modulation of IFN-ß response to S. pneumoniae in epithelial cells.

Inequities in consistent condom use among sexually experienced undergraduates in mainland China: implications for planning interventions.

BACKGROUND: Since pre-exposure prophylaxis (PrEP) is mainly prescribed to high-risk uninfected individuals, consistent condom use (CCU) continues to be recommended as an inexpensive, feasible, practical and acceptable way to prevent the general population from acquiring and transmitting HIV through sexual intercourse. The objective of this cross-sectional study was to compare the relative importance of various determinants of CCU among sexually experienced undergraduates in mainland China so as to assess and subsequently to suggest ways to eliminate inequities in its use. METHOD: From September 10, 2018, to January 9, 2019, an anonymous self-administered online questionnaire was voluntarily completed by 12,750 participants distributed across 30 provinces in mainland China (except for Tibet). The present analysis was restricted to 2054 sexually experienced undergraduates. Pearson's chi-square test and Logistic regression models were chosen to analyze the factors associated with CCU. RESULTS: The overall rate of CCU was 61.3% [95% confidence interval (CI) = 59.2-63.4%]. CCU was inequitably distributed since enabling factors exerted greater effects than predisposing and need variables. Compared with heterosexual men, heterosexual women [adjusted odds ratio (AOR) = 0.78, 95% confidence interval (CI):0.64-0.96)], non-heterosexuals men (AOR = 0.64, 95% CI:0.45-0.92) and women (AOR = 0.68, 95% CI:0.47-0.99) were less prone to using condoms consistently. Those with more resources [i.e., higher levels of self- efficacy for condom use (AOR = 2.86, 95% CI:2.35-3.49) and being knowledgeable of the national AIDS policy (AOR = 1.50, 95% CI:1.23-1.82)], and those with lower need for condoms [i.e., late initiation of sexual activity (AOR = 1.34, 95% CI:1.09-1.64) and single sexual partner (AOR = 1.68,95% CI:1.21-2.33)] were more likely to be consistent condom users. CONCLUSIONS: In order to increase consistency of condom use and simultaneously reduce the remaining inequities, a comprehensive intervention measure should be taken to target heterosexual women, non-heterosexual men and women, and those with higher need for condoms, improve their condom use self- efficacy and raise their awareness of the national AIDS policy.

Application of the Chinese version of Zelaya's HIV-related stigma scale to undergraduates in mainland China.

BACKGROUND: This cross-sectional study aims to validate the Chinese version of Zelaya's HIV-related Stigma Scale (CVZHSS) among a large undergraduate sample in mainland China, and apply it to measure the level of different dimensions of stigma and their respective determinants. METHODS: From September 10, 2018, to January 9, 2019, a total of 10,665 eligible undergraduates conveniently drawn from 30 provinces in mainland China (except for Tibet) completed the self-designed online questionnaire distributed via sojump.com voluntarily, anonymously and confidentially. Both exploratory and confirmatory factor analyses (EFA and CFA) were first performed to test its construct validity, Cronbach's alpha was then used to assess its internal consistency, and Logistic regression analyses were finally carried out to identify predictors of various dimensions of stigma. RESULTS: As expected from the original model, four factors (i.e., "fear of casual transmission", "moral judgment", "personal stigma" and "perceived community stigma") were extracted using principal component analysis with varimax rotation, accounting for 63.26% of the total variance. The CFA further confirmed the four-factor construct (CFI = 0.92, GFI = 0.91, RMSEA = 0.07). In addition, all the four factors demonstrated acceptable internal consistency with Cronbach's alpha ranging from 0.83 to 0.92. Stigma as measured by "fear of casual transmission" (74.4%), "moral judgement" (61.6%), "personal stigma" (79.0%) and "perceived community stigma"(36.5%) is highly prevalent among undergraduates. Except for non-freshmen, less knowledge about HIV and unsafe sex which were consistently associated with higher levels of stigma in all four dimensions, other eight variables including gender, residential area, major, sexual orientation, having ever being tested perception of HIV risk, willingness to utilize HTC service and awareness of the national AIDS policy played differential roles in affecting different dimensions of stigma. CONCLUSIONS: The CVZHSS is a reliable and valid measurement tool and can be used to identify undergraduates with high levels of stigma. However, the four dimensions (Fear, moral judgement, personal stigma and perceived community stigma) were respectively influenced by different determinants, and thus should be treated independently when designing, implementing and evaluating stigma reduction programs.

Secondary organic aerosols in Jinan, an urban site in North China: Significant anthropogenic contributions to heavy pollution.

Secondary organic aerosols (SOAs) are an important component of particulates, but whether biogenic SOAs (BSOAs) or anthropogenic SOAs (ASOAs) are the dominant contributors to haze pollution remains poorly characterized. In this study, particulate samples were collected from September 2014 to August 2015 at an urban site in Jinan, which is the capital of Shandong Province and a typical city in the North China Plain. The PM2.5 samples were analyzed for BSOA (isoprene (SOAI) and monoterpenes (SOAM)) and ASOA (aromatic (SOAA)) tracers. The concentrations of the SOAA tracer (1.1 ±â€¯1.0 ng/m3) were lowest, and those of SOAI tracers (41.8 ±â€¯86.2 ng/m3) were highest, with the concentrations of SOAM tracers (19.4 ±â€¯9.9 ng/m3) being intermediate. The SOAI tracers were more abundant in the summer and less abundant in the winter. Both SOAI and SOAM increased with increasing ozone level but decreased with increasing NOx level. Correlation analysis revealed a good correlation between 2,3-dihydroxy-4-oxopentanoic acid and levoglucosan levels in three seasons. These results suggested that biomass burning activities occurring in the NCP can enhance the emissions of aromatics and should be controlled, especially in the autumn and winter. SOA tracers were classified according to pollution degree, and the results showed that as pollution increases, the contributions of SOAA increase. These results indicate that reducing anthropogenic emissions is necessary to prevent SOA pollution, especially during heavy pollution episodes.

PDGF-D promotes dermal fibroblast invasion in 3-dimensional extracellular matrix via Snail-mediated MT1-MMP upregulation.

Increasing attention has been focused on the malignant tumor microenvironment, which plays important roles in tumor occurrence, progression and metastasis. Fibroblasts are recruited by platelet-derived growth factor (PDGFs) and invade the tumor microenvironment. In the PDGF family, PDGF-B has been reported to play an important role in the recruitment and invasion programs. However, whether PDGF-D plays a role in these programs remains unclear. We generated a recombinant plasmid expressing human PDGF-D and transfected the plasmid to dermal fibroblasts to examine the effects on cell invasive activities in 3D type I collagen gels. PDGF-D plasmid transfection enhanced fibroblast invasive activities both in invasive cell numbers and invasion depth in 3D collagen gels. These effects were blocked by Snail-specific siRNA transfection. PDGF-D transfection significantly induced Snail expression at both mRNA and protein levels. PDGF-D further upregulated MT1-MMP mRNA and protein expressions and this was inhibited when Snail was knocked down by siRNA. Both Snail and MT1-MMP expressions in fibroblasts and cellular invasive activities in 3D collagen induced by PDGF-D were inhibited by LY294002, SP600125, and U1026, the inhibitors of PI3K, JNK, and ERK1/2 signaling pathways, respectively. However, no effects were observed in response to the P38MAPK signaling pathway inhibitor SB203580. These effects of PDGF-D were confirmed by using the culture supernatants of the transfectants. Taken together, these data demonstrate that PDGF-D plays important roles in the recruitment and invasion programs of fibroblasts via the activation of PI3K, JNK and ERK1/2 signaling pathways, and upregulation of Snail and downstream effecter MT1-MMP. These findings indicate that PDGF-D is an important player in the tumor microenvironment for fibroblast recruitment.

Mucosal immunization with the live attenuated vaccine SPY1 induces humoral and Th2-Th17-regulatory T cell cellular immunity and protects against pneumococcal infection.

Mucosal immunization with attenuated vaccine can protect against pneumococcal invasion infection, but the mechanism was unknown. Our study found that mucosal delivery with the live attenuated SPY1 vaccine strain can confer T cell- and B cell-dependent protection against pneumococcal colonization and invasive infection; yet it is still unclear which cell subsets contribute to the protection, and their roles in pneumococcal colonization and invasion remain elusive. Adoptive transfer of anti-SPY1 antibody conferred protection to naive µMT mice, and immune T cells were indispensable to protection examined in nude mice. A critical role of interleukin 17A (IL-17A) in colonization was demonstrated in mice lacking IL-17A, and a vaccine-specific Th2 immune subset was necessary for systemic protection. Of note, we found that SPY1 could stimulate an immunoregulatory response and that SPY1-elicited regulatory T cells participated in protection against colonization and lethal infection. The data presented here aid our understanding of how live attenuated strains are able to function as effective vaccines and may contribute to a more comprehensive evaluation of live vaccines and other mucosal vaccines.

Interleukin 17A promotes pneumococcal clearance by recruiting neutrophils and inducing apoptosis through a p38 mitogen-activated protein kinase-dependent mechanism in acute otitis media.

Streptococcus pneumoniae is a Gram-positive and human-restricted pathogen colonizing the nasopharynx with an absence of clinical symptoms as well as a major pathogen causing otitis media (OM), one of the most common childhood infections. Upon bacterial infection, neutrophils are rapidly activated and recruited to the infected site, acting as the frontline defender against emerging microbial pathogens via different ways. Evidence shows that interleukin 17A (IL-17A), a neutrophil-inducing factor, plays important roles in the immune responses in several diseases. However, its function in response to S. pneumoniae OM remains unclear. In this study, the function of IL-17A in response to S. pneumoniae OM was examined using an in vivo model. We developed a model of acute OM (AOM) in C57BL/6 mice and found that neutrophils were the dominant immune cells that infiltrated to the middle ear cavity (MEC) and contributed to bacterial clearance. Using IL-17A knockout (KO) mice, we found that IL-17A boosted neutrophil recruitment to the MEC and afterwards induced apoptosis, which was identified to be conducive to bacterial clearance. In addition, our observation suggested that the p38 mitogen-activated protein kinase (MAPK) signaling pathway was involved in the recruitment and apoptosis of neutrophils mediated by IL-17A. These data support the conclusion that IL-17A contributes to the host immune response against S. pneumoniae by promoting neutrophil recruitment and apoptosis through the p38 MAPK signaling pathway.

Mucosal immunization with recombinant fusion protein DnaJ-ΔA146Ply enhances cross-protective immunity against Streptococcus pneumoniae infection in mice via interleukin 17A.

Pneumolysin (Ply) and its variants are protective against pneumococcal infections in animal models, and as a Toll-like receptor 4 agonist, pneumolysin has been reported to be a mucosal adjuvant. DnaJ has been approved as a useful candidate vaccine protein; we therefore designed novel fusion proteins of DnaJ with a form of Ply that has a deletion of A146 (ΔA146Ply-DnaJ [the C terminus of ΔA146Ply connected with the N terminus of DnaJ] and DnaJ-ΔA146Ply [the C terminus of DnaJ connected with the N terminus of ΔA146Ply]) to test whether they are protective against focal and lethal pneumococcal infections and their potential protective mechanisms. The purified proteins were used to intranasally immunize the animals without additional adjuvant. Immunization with DnaJ-ΔA146Ply or DnaJ plus ΔA146Ply (Ply with a single deletion of A146) could significantly reduce S. pneumoniae colonization in the nasopharynx and lung relative with DnaJ alone. Additionally, we observed the best protection for DnaJ-ΔA146Ply-immunized mice after challenge with lethal doses of S. pneumoniae strains, which was comparable to that achieved by PPV23. Mice immunized with DnaJ-ΔA146Ply produced significantly higher levels of anti-DnaJ IgG in serum and secretory IgA (sIgA) in saliva than those immunized with DnaJ alone. The production of IL-17A was also striking in DnaJ-ΔA146Ply-immunized mice. IL-17A knockout (KO) mice did not benefit from DnaJ-ΔA146Ply immunization in colonization experiments, and sIgA production was impaired in IL-17A KO mice. Collectively, our results indicate a mucosal adjuvant potential for ΔA146Ply and that, without additional adjuvant, DnaJ-ΔA146Ply fusion protein exhibits extensive immune stimulation and is effective against pneumococcal challenges, properties which are partially attributed to the IL-17A-mediated immune responses.

Contradictory response of ozone and particulate matter concentrations to boundary layer meteorology.

At the present stage, collaborative control of particulate matter and ozone pollution has become a modern challenge. The atmospheric boundary layer height (ABLH) is an important meteorological parameter for the sources and sinks of air pollutants. It is generally recognized that the reduction of boundary layer is conducive to the accumulation of pollutants. However, in recent years, some studies have shown that the relationship between ABLH and ozone is not negatively correlated. Here, we analyzed the spatial distribution characteristics of PM2.5 and ozone exceedance in China from 2015 to 2022. The relationships between particulate pollution and ozone pollution and boundary layer meteorology were discussed. The key to coordinated control is to control the PM2.5 concentration in the winter and ozone in summer. Moreover, the two have different responses to meteorological factors, especially to the ABLH. Low temperature and low ABLH are conducive to the deterioration of particulate pollution, but high temperature and high ABLH are conducive to the occurrence and development of ozone pollution. The response of ozone to ABLH is contrary to previous studies in Europe and the United States. Moreover, an abnormal positive correlation was observed for PM2.5 and ABLH in Southwest China, which was mainly due to the impact of biomass combustion in Southeast Asia.