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Abstract In past decades, China has experienced substantial economic growth and industrialization. However, the effects of vast development of China on Hg input to the nearby oceans are still unclear. In this study, four representative 210Pb-dated sediment cores were collected in the central and southern part of Bohai sea to investigate vertical changes of Hg contents and explore the relationship between the Hg deposition and pollution history in this region utilizing a large amount of information available. The results indicated that Hg median concentrations of sediment core B62, B66, JQ17 and HZ24 were 0.043 mg/kg, 0.054 mg/kg, 0.033 mg/kg and 0.018 mg/kg respectively, among which, B66 in Yellow river estuary and B62 in central part of Bohai Sea had higher concentrations and HZ24 in Bohai Strait had a lower concentration. 210Pb profile appeared as a three segments model in the core B62, but as many steps of decay with depth in B66. For HZ24, 210Pb activity only fluctuated with depth without any discernible trend. Sedimentary rates of these cores decreased as follows: B66＞B62＞JQ17＞HZ24. Vertical distributions of Hg concentrations in sediment cores were totally different from each other. Hg concentrations in sediment core B62 experienced an initial fluctuation followed by a decreasing trend, while sediment core HZ24 almost showed the uniform decreasing trends from the surface to the bottom. There were three segments of variation in sediment cores JQ17: initial fluctuation followed by an obviously decreasing tendency and then a converted variation from surface to bottom. Hg contents changes in core B62 might reflect the additive effects from atmospheric deposition at a larger scale and the river-delivered sediment accumulation, while Hg vertical changes in B66 mainly had a close relationship with the input of Yellow river. The converted variation at the bottom section in sediment cores JQ17 was inferred to have some relationship with the Chengbei platform construction in the corresponding periods. Highlights • Hg median content in each sediment core was 0.043, 0.054, 0.033 and 0.018 mg/kg. • Hg vertical distribution in B66 had relationships with input of Yellow river. • Hg change in B62 reflected additive effect of atmospheric deposition ＆river input. • Hg profile showed uniform rising trends in HZ24 from bottom to surface. • Inversion of Hg distribution in Q17 was related with platform construction. [ABSTRACT FROM AUTHOR]

Background The functionality of lncRNA snaR has only been characterized in breast cancer and colon cancer. The aim of the current study is to explore the involvement of lncRNA snaR in ovarian carcinoma (OC). Materials and methods Expression of lncRNA snaR and GRB2-associated binding protein 2 (GAB2) in plasma of both patients with OC and healthy females was detected by qRT-PCR. Application value of plasma lncRNA snaR in the diagnosis of OC was evaluated by ROC analysis. Correlation between plasma lncRNA snaR and GAB2 was analyzed by Pearson correlation coefficient. LncRNA snaR and GAB2 expression vectors as well as GAB2 siRNA were transfected into cells of human OC cell lines, and the effect on lncRNA snaR expression, GAB2 expression and cell proliferation was detected by qRT-PCR, western blot and CCK-8 assay. Results It was observed that plasma levels of lncRNA snaR and GAB2 were significantly higher in OC patients than those in healthy controls. In effect, high levels of plasma lncRNA snaR and GAB2 distinguished OC patients from healthy controls. Plasma lncRNA snaR and GAB2 were positively correlated in OC patients but not in healthy controls. LncRNA snaR overexpression promoted cancer cell proliferation and upregulated GAB2 expression. Conclusions GAB2 overexpression also promoted cancer cell proliferation but showed no significant effects on lncRNA snaR expression, while GAB2 siRNA silencing significantly attenuated the enhancing effects of lncRNA snaR overexpression on cancer cell proliferation. LncRNA snaR may promote proliferation of ovarian carcinoma cells by upregulating GAB2 expression. [ABSTRACT FROM AUTHOR]

HSP60 has been proved to be closely related to atherosclerosis due to its antigenicity. To determine this antigenicity effect, the ApoE−/− mice were fed with western-type diet and HSP60 was administrated orally or subcutaneously (SC) for potential vaccine against atherosclerosis. Here, we observed the ApoE−/− mice with oral HSP60 administration group showed a significant reduction in plaque size at the aortic root; accompanied by increased MSDCs (CD11b + Gr1 + ) in peripheral blood and spleen which was mostly composed of M-MDSCs (CD11b + LY6G − LY6C high ), and increased plasma IL-10 and splenic Foxp3, Arg1, iNOS mRNA as well as decreased plasma IFN-γ and splenic T-bet mRNA compared to control group. Surprisingly, ApoE−/− mice with subcutaneous HSP60 administration group showed contrary results and their MDSCs were mostly composed of G-MDSCs (CD11b + LY6G + LY6C low ). As expected, both PBS-oral and PBS-SC groups showed no significant effects on both the immune response and atherosclerotic plaque formation. In contrast, subcutaneous administration of HSP60 causes the opposite response. Thus, we propose the proper method for administering HSP60 as a new immunologic agent for prevention and treatment of atherosclerosis. [ABSTRACT FROM AUTHOR]

Whether household air pollution is associated with dementia risk remains unknown. This study examined the associations between solid fuel use for cooking and heating (the main source of household air pollution) and dementia risk. This analysis included data on 11,352 participants (aged 45+ years) from the 2011 wave of China Health and Retirement Longitudinal Study, with follow-up to 2018. Dementia risk was assessed by a risk score using the Rotterdam Study Basic Dementia Risk Model (BDRM), which was subsequently standardized for analysis. Household fuel types of cooking and heating were categorized as solid (e.g., coal and crop residue) and clean (e.g., central heating and solar). Multivariable analyses were performed using generalized estimating equations. Moreover, we examined the joint associations of solid fuel use for cooking and heating with the BDRM score. After adjusting for potential confounders, we found an independent and significant association of solid (vs. clean) fuel use for cooking and heating with a higher BDRM score (e.g., β = 0.17 for solid fuel for cooking; 95% confidence interval [CI]: 0.15–0.19). Participants who used solid (vs. clean) fuel for both cooking and heating had the highest BDRM score (β = 0.32; 95% CI: 0.29–0.36). Subgroup analysis suggested stronger associations in participants living in rural areas. Solid fuel use for cooking and heating was independently associated with increased dementia risk in Chinese middle-aged and older adults, particularly among those living in rural areas. Our findings call for more efforts to facilitate universal access to clean energy for dementia prevention. • Solid fuel use for cooking and heating was independently associated with increased dementia risk. • Participants who used solid fuel for both cooking and heating had the highest dementia risk. • Stronger association of solid fuel use with increased dementia risk was found in participants living in rural areas. [ABSTRACT FROM AUTHOR]

Thirty-seven lactic acid bacteria (LAB) strains were isolated from traditional dry sausages collected from Northeast China, including Latilactobacillus sakei (29 strains), Lactiplantibacillus plantarum (4 strains), Latilactobacillus curvatus (2 strains), Weissella hellenica (1 strain), and Lactococcus lactis (1 strain). Some LAB strains had tolerance to high concentrations of sodium chloride (6%), sodium nitrite (150 mg/L NaNO 2), and acid (pH 4.0). They showed good growth and acidification properties and antimicrobial activity. Among them, five LAB strains that exhibited the best technological properties were selected and inoculated in the sausage model to explore their roles in flavor development. The contents of total free amino acids (FAAs) decreased ranging from 109.11 mg/g to 58.06 mg/g. A total of 46 volatile compounds were identified and the contents of volatile compounds increased in the sausage model during fermentation. Partial least squares regression analysis showed that Lb. sakei HRB10, Lb. plantarum MDJ2, W. hellenica HRB6, and Lc. lactis HRB0 promoted the generation of FAAs and volatile compounds in the sausage model. These findings demonstrated that the autochthonous LAB species are promising for the production of sausage with better flavor and fermentation performance. [Display omitted] • Thirty-seven LAB strains were isolated from traditional dry fermented sausages. • The selected strains exhibited high tolerance to salt, sodium nitrite, and acid. • LAB inoculation promoted free amino acid (FAA) and flavor generation. • The FAAs were responsible for the differences in the flavor of sausage models. [ABSTRACT FROM AUTHOR]

Oxidative stress is a causal factor and key promoter of a variety of cardiovascular diseases associated with apoptotic cell death by causing deregulation of related genes. Though carvedilol, a β-adrenergic blocker, has been shown to produce cytoprotective effects against cardiomyocyte apoptosis, the mechanisms are not fully understood. The present study was designed to investigate whether the beneficial effects of carvedilol are related to microRNAs which have emerged as critical players in cardiovascular pathophysiology via post-transcriptional regulation of protein-coding genes. In vivo, we demonstrated that carvedilol ameliorated impaired cardiac function of infarct rats and restored miR-133 expression. In vitro, carvedilol protected cardiomyocytes from H2O2 induced apoptosis detected by TUNEL staining and MTT assays , and increased miR-133 expression in cardiomyocytes. Overexpression of miR-133, a recognized anti-apoptotic miRNA, produced similar effects to carvedilol: reduction of reactive oxygen species (ROS) and malondialdehyde (MDA) content and increment of superoxide dismutase (SOD) activity and glutathione peroxidase (GPx) level, so as to protect cardiomyocytes from apoptosis by downregulating caspase-9 and caspase-3 expression in the presence of H2O2. Transfection with AMO-133 (antisense inhibitor oligodeoxyribonucleotides) alone abolished the beneficial effects of carvedilol. Caspase-9-specific inhibitor z-LEHD-fmk, caspase-3-specific inhibitor z-DEVD-fmk, caspase-9 siRNA and caspase-3 siRNA were used to establish caspase-3 as a downstream target of miR-133. In conclusion, our data indicated that carvedilol protected cardiomyocytes by increasing miR-133 expression and suppressing caspase-9 and subsequent apoptotic pathways. [ABSTRACT FROM AUTHOR]

The traditional dry sausage is highly appreciated in China because of its unique quality characteristics, but it contains high salt content. Hence, this study aimed to evaluate the effects of lactic acid bacteria (LAB) comprising Lactobacillus sakei (LS), Lactobacillus curvatus (LC), Lactobacillus plantarum (LP), and Weissella hellenica (WH) on the quality attributes of the reduced-salt dry fermented sausages. The results indicated that the LP sausage showed higher (P < 0.05) shear force value compared to the other sausages, while the LP, LC, and WH sausages had higher (P < 0.05) lightness values than the control sausages. Seventy-six volatile compounds were detected, and nine compounds were identified as the key differential volatile compounds among the sausages based on partial least squares discriminant analysis. Clustering analysis of electronic nose results corresponded well to the volatile compound results. The sensory evaluation confirmed that the inoculation with LC and LP had a positive impact on the aroma, color, and hardness attributes of the reduced-salt sausages. Besides, partial least squares regression analysis further indicated that L. curvatus and L. plantarum could be used as the potential starter cultures to manufacture reduced-salt dry fermented sausage having improved texture, color, and flavor. [Display omitted] • The LP sausage shows higher shear force value compared to the other sausages. • The LP, LC, and WH sausages have higher lightness values than the control sausages. • Seventy-six volatile compounds are detected in dry fermented sausage. • Sensory attributes correlate with the key volatile compounds using PLSR analysis. • L. curvatus and L. plantarum can improve the quality of reduced-salt dry sausage. [ABSTRACT FROM AUTHOR]

Abstract: Three-dimensional (3D) dendrite-shaped CuO hollow micro/nanostructures have been prepared via a Kirkendall-effect-based approach for the first time and have been demonstrated as a high-performance anode material for lithium-ion batteries. The as-prepared hollow structures were investigated by scanning electron microscopy, transmission electron microscopy, X-ray diffraction, and electrochemical properties. A CuO hollow structure composed of nanocubes outside and a dense film inside was selected as a typical example of the optimized design; it exhibited significantly improved cyclability at a current rate of 0.5C, with the average Coulombic efficiency of ∼97.0% and 57.9% retention of the discharge capacity of the second cycle after 50 cycles. The correlation between the structure features of the hollow CuO and their electrochemical behavior was discussed in detail. Smaller size of primary structure and larger internal space of electrode materials are crucial to better electrochemical performance. This work represents that Kirkendall effect is a promising method to fabricate excellent hollow electrode materials for Li-ion batteries. [Copyright &y& Elsevier]

This study evaluated the effect of different sugar smoking times on the flavour profiles of chicken drumsticks using an electronic nose (E-nose), electronic tongue (E-tongue), and headspace solid-phase microextraction gas chromatography-mass spectrometry (HS-SPME/GC-MS). The moisture content, water activity, pH, and L *-value decreased from 71.26% to 65.23%, 0.987 to 0.979, 6.66 to 5.36, and 61.84 to 52.34, respectively (P < 0.05). The a *-value and b *-value increased from 4.96 to 9.65 and 16.61 to 26.45, respectively (P < 0.05) with the increase in smoking times. Seventy-five volatile compounds were identified, and 18 volatile compounds were identified as key odour compounds and among them seven key volatile compounds with variable importance in projection (VIP) > 1 were detected. Principal component analysis of E-nose, E-tongue, and HS-SPME/GC-MS indicated that 3-, 4-, and 5-min smoking samples had similar odour and taste profiles. Sensory analysis indicated that the 4-min sample had increased overall acceptability. The correlation analysis of E-nose and key volatile compounds with odour activity value > 1 and VIP >1 confirmed that W1C, W3C, and W5C sensors were sensitive to aromatic compounds, and W2S sensor was sensitive to ketones. These results may provide guidance for smoked chicken producers to reasonably control flavour formation. • A total of 75 volatile compounds were detected in smoked chicken drumsticks. • Eighteen key volatile compounds were identified. • The 3-, 4-, and 5-min smoked samples had similar odour and taste profiles. • The 4-min smoked chicken drumsticks had increased sensory acceptability. [ABSTRACT FROM AUTHOR]

This study was to investigate the succession of the bacterial community in Harbin dry sausages during fermentation and its correlation to the sausage flavour. The results showed that Staphylococcus count increased but the moisture content and water activity decreased (P < 0.05). The lactic acid bacteria count first increased and then decreased, while the pH showed an opposite trend during a twelve-day fermentation (P < 0.05). According to a single molecule real time sequencing analysis, Lactobacillus sakei and Staphylococcus xylosus were the predominant bacterial species over the entire fermentation period. A total of 79 volatile compounds were detected using the headspace solid phase microextraction gas chromatography-mass spectrometry. Furthermore, the correlation between the core bacteria (top 30) and the major volatile compounds was explored, which highlighted that three bacterial species (Lb. sakei , S. xylosus and Weissella hellenica) were significantly correlated with the major volatile compounds, such as 2,3-butanediol, ethanol, 3-hydroxy-2-butanone, ethyl hexanoate and ethyl lactate. The results may provide a theoretical basis for improving the flavour and overall quality of dry sausage. • Lactobacillus sakei and Staphylococcus xylosus were the dominant bacterial species. • Seventy-nine volatile compounds were detected in Harbin dry sausages. • L. sakei , S. xylosus and W. hellenica were correlated with the volatile compounds. [ABSTRACT FROM AUTHOR]

The objective of this study was to explore the correlation between bacterial communities and volatile compounds in traditional dry sausages from different regions in Northeast China. The bacterial community structure of dry sausages from five different regions as determined by high-throughput sequencing technology demonstrated that Firmicutes and Proteobacteria were the predominant phyla; Lactobacillus , Staphylococcus , Leuconostoc , Lactococcus and Weissella were the predominant genera; and Staphylococcus xylosus , Lactobacillus sakei , Weissella hellenica , Leuconostoc citreum , Lactococcus raffinolactis and Lactobacillus plantarum were the predominant species. Meanwhile, a total of 120 volatile compounds were detected in sausages from five different regions and mainly included alcohols, acids, aldehydes, ketones, esters and terpenes. Furthermore, the potential correlations between the core bacteria and major volatile compounds (64) were explored based on Spearman's correlation analysis. Positive correlations were found between W. hellenica , Lb. sakei , Lactococcus lactis , Lactobacillus alimentarius , Lb. plantarum and carboxylic acids and alcohols. Lc. lactis , Lb. alimentarius and Lb. plantarum were associated with the production of most esters, aldehydes and ketones. This study provides a deep insight into the relationship between the bacterial community and the volatile flavour profile of dry sausages, which may be helpful for the production of fermented dry sausages. Image 1 • The pdredominant phyla were Firmicutes and Proteobacteria in traditional dry sausage. • A total of 120 volatile compounds were detected in the five traditional sausages. • Five core bacteria improved the formation of volatile compounds in dry sausage. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate the effects of NaCl reduction (2.5% 2.0%, 1.5% and 1.0%) on the bacterial growth, physicochemical characteristics, flavour profile and sensory traits of fermented dry sausage. The moisture content, water activity and lactic acid bacteria count increased as the NaCl level decreased (P < 0.05), contributing to decreases in pH (P < 0.05). A total of 50 volatile compounds were identified, and increases in volatile compounds, such as acetone, 3-hydroxy-2-butanone, with high odour activity values derived from carbohydrate metabolism and lipid oxidation may contribute to flavour development (P < 0.05). Additionally, the increased Staphylococcus spp. counts in sausages with 2.0% and 2.5% NaCl contributed to the increased contents of ethyl octanoate, ethyl butyrate and ethyl acetate (P < 0.05). Sensory evaluation showed higher scores for taste, chewiness and aroma in sausages with 2.0% and 2.5% NaCl. Therefore, it can be concluded that 2.0% NaCl can be employed as the desired addition level in fermented sausage to achieve better quality and flavour. • Sausages with reduction in NaCl level had higher moisture content and water activity. • The reduction of NaCl level increased lactic acid bacteria population. • Volatile compounds in fermented sausage during fermentation were identified. • 2.0% NaCl can be employed as the desired addition level in fermented sausage. [ABSTRACT FROM AUTHOR]

Pediococcus pentosaceus (Pp) , Lactobacillus curvatus (Lc) , Lactobacillus sakei (Ls) and Staphylococcus xylosus (Sx) were evaluated to determine their roles in the quality characteristics and flavor formation in Harbin dry sausage. The inoculation of dry sausages with bacterial strains, especially mixed strains (Pp + Sx + Lc and Pp + Sx + Ls), significantly decreased the moisture content and water activity. Compared with the sausages inoculated with a single strain and non-inoculated, those inoculated with mixed strains had shorter transverse relaxation time T 21 that represents the immobilized water (P < 0.05) after a nine-day fermentation. The texture profile analysis showed that inoculation with bacterial strains increased the hardness and springiness of sausages. The sausages inoculated with mixed strains showed higher a *-values (P < 0.05). Furthermore, the percentages of some aldehydes, ketones, alcohols, acids and esters in the sausage inoculated with Pp + Sx + Lc were significant higher than that in control sausages (P < 0.05), which may be derived from carbohydrate catabolism (such as 3-hydroxy-2-butanone), amino acid metabolism (such as 3-phenylpropanol, 2,3-butanediol, phenylethyl alcohol, 2-methyl-propanal, 2-methyl-butanal and 3-methyl-butanal), β-lipid oxidation (such as 2-pentanone, 2-heptanone and 2-nonanone) and esterification (such as ethyl esters). • Bacterial fermentation promoted the decrease in moisture content and water activity. • Bacterial fermentation improved the hardness and springiness of sausage. • The fermentation with multiple bacterial strains had higher percentages of favorable volatile compounds. [ABSTRACT FROM AUTHOR]

The technological properties and flavour formation potential of yeast strains isolated from traditional dry fermented sausages were evaluated. A total of 46 yeast strains were isolated and characterized at the strain level by genotyping. Among them, 34 strains were selected for evaluation of technological properties (tolerance to acid, salt, and sodium nitrite stresses; proteolytic and lipolytic activities; and biogenic amine formation capacity) based on their genetic profiles. Then, seven strains (Debaryomyces hansenii HRB2, SH4, and HG2; Torulaspora delbrueckii DQ3 and HG7; Pichia kudriavzevii MDJ1; and Candida zeylanoides DQ7) were selected to investigate their flavour formation potential in a fermented sausage model. A total of 56 volatile compounds were detected in all models, of which 17 volatile compounds were the most important flavour contributors with an odour activity value (OAV) > 1. The most remarkable result was the significant production of acid, alcohol, and esters in the inoculated models, such as acetic acid, hexanoic acid, ethanol, phenethyl alcohol, ethyl acetate, and ethyl hexanoate. Of all the strains, D. hansenii SH4 was considered to be the best flavour producer because it produced multiple compounds with the highest OAVs, which are associated with the development of desirable sensory characteristics in dry sausages. • A total of 46 yeast strains were isolated from traditional dry fermented sausages. • Intraspecific genetic diversity of yeast strains was explored using ISSR-PCR. • Eight strains exhibited high tolerance to acid, salt, and sodium nitrite stresses. • Seven strains showed specific capacities to produce acids, alcohols, and esters. • Debaryomyces hansenii SH4 produced multiple compounds with high odour activity value. [ABSTRACT FROM AUTHOR]

Cyclin D1 (CCND1) has been identified as a metastatic promoter in various tumors including lung adenocarcinoma (LUAD), a subtype of non small cell lung cancer (NSCLC). The previous observation revealed that CCND1 was upregulated in NSCLC and predicted poor prognosis of LUAD patients. In this study, we examined a chaperonin containing TCP1 subunit 5 (CCT5) protein interacts with CCND1 in LUAD. Immunofluorescence demonstrated the co-localization of CCT5 and CCND1 protein in LUAD cells. CCT5 expression was detected with both immunohistochemistry (IHC) and bioinformatics analyses. Similar with the expression pattern of CCND1, CCT5 displayed a high level in LUAD tissues compared to non cancerous lung specimens. Patients with high CCT5 expression showed a significant shorter overall survival relative to those with low expression level. Furthermore, upregulated CCT5 exhibited significant positive correlation with TNM stage of LUAD patients in both IHC analyses and bioinformatics. Knocking down CCT5 remarkably inhibited LUAD cell migration and invasion in vitro by inactivating PI3K/AKT and its downstream EMT signals, which could abrogated the accelerated migration and invasion caused by CCND1 overexpression. In summary, our study discovered a highly expressed protein CCT5 in LUAD which interacted with CCND1 and promoted migration and invasion of LUAD cells by positively moderating PI3K/AKT-induced EMT pathway. ∙ CCT5 functions as a role for promoting tumor progression. ∙CCT5 interacts with CCND1 to promote the migration and invasion of lung carcinoma. ∙Patients with high CCT5 expression showed a poor overall survival prognosis. [ABSTRACT FROM AUTHOR]

Perinatal asphyxia often results in neonatal cerebral hypoxia-ischemia (HI), which is associated with high mortality and severe long-term neurological deficits in newborns. Currently, there are no effective drugs to mitigate the functional impairments post-HI. Previous studies have shown that fibroblast growth factor 21 (FGF21) has a potential neuroprotective effect against brain injury. However, the effect of FGF21 on neonatal HI brain injury is unclear. In the present study, both in vivo and in vitro models were used to assess whether recombinant human FGF21 (rhFGF21) could exert a neuroprotective effect after HI and explore the associated mechanism. The results showed that the rhFGF21 treatment remarkably reduced the infarct volume, ameliorated the body weight and improved the tissue structure after HI in neonatal rats. In addition, the rhFGF21 treatment lengthened the running endurance times in the rotarod test and decreased the mean escape latencies and increased the number of platform crossings in the Morris water maze test at 21 d post-HI insult. In contrast, the FGFR1 inhibitor PD173074 and PI3K inhibitor LY294002 partially reversed these therapeutic effects. In isolated primary cortical neurons, the rhFGF21 treatment protected primary neurons from oxygen-glucose deprivation (OGD) insult by inhibiting neuronal apoptosis and promoting neuronal survival. Both our in vivo and in vitro results reveal that rhFGF21 could inhibit neuronal apoptosis by activating the PI3K/Akt signaling pathway via FGF21/FGFR1/β-klotho complex formation. Therefore, rhFGF21 may be a promising therapeutic agent for promoting functional recovery after HI-induced neonatal brain injury. • rhFGF21 reduces the brain infarct volume and ameliorates the histological structure. • rhFGF21 improves motor and learning disabilities in rats after hypoxia-ischemia. • rhFGF21 activates the PI3K/Akt pathway via FGFR1/β-klotho post hypoxia-ischemia. • rhFGF21 attenuates OGD-induced primary cortical neuronal death. • rhFGF21 protects neurons against OGD injury by inhibiting neuronal apoptosis. [ABSTRACT FROM AUTHOR]

Ascosphaera apis (Onygenales: Ascosphaeraceae) is a chalkbrood causing pathogen in honeybees. Recently, chemicals have been used against this disease. Consequently, the abuse of chemicals has caused serious impacts on the environment and honey quality and on honeybee colonies themselves. Therefore, the search for biological control options should be the priority for controlling chalkbrood disease. In this experiment, we employed restriction enzyme mediated integration (REMI) to construct mutants (transformants) with growth inhibition on A. apis in honeybees using the Trichoderma atroviride T23 wild strain. The integration of the plasmid pBluescript KS-EH1 into the REMI mutants was confirmed by PCR and Southern hybridization. As a result, ten single-copied T. atroviride T23 transformants were successfully identified. Furthermore, culture filtrates of the transformants, their wild strain and Shabaijing (a commercial fungicide, ethyl ethylsulfonothiolate) were tested to compare their in vitro growth inhibition capability on A. apis . The results demonstrated that transformants Tat5 and Tat6 had the highest growth inhibition activity with the minimal fungicidal concentration (v/v) of 3.5–4.5%. Thus, the Trichoderma transformants constructed by REMI could be used as potential biological agents against the growth of fungal diseases in bee hives. Further refinement and strategy development for the integrative use of this result are vital future plans. [ABSTRACT FROM AUTHOR]

Neonatal hypoxic-ischemic (HI) brain injury remains a devastating clinical disease associated with high mortality and lifetime disability. Neonatal HI injury damages the architecture of neurovascular unit (NVU), thus, therapy targeting the NVU may provide effective neuroprotection against HI. This study was designed to investigate whether fibroblast growth factor 10 (FGF10) protected the NVU against HI and afforded observable neuroprotection in a rat model of neonatal HI brain injury. The results showed that FGF10 treatment significantly reduced brain damage post HI, characterized by reduction in brain infarct volume and tissue loss. Further interesting findings showed that FGF10 treatment exerted neuroprotective effects on HI brain injury in neonate rats through protecting the NVU against HI, evidenced by inhibition of neuronal cell apoptosis, suppression of gliosis, and amelioration of blood-brain barrier disruption. Collectively, our study indicates that FGF10 treatment exhibits great potential for protecting NVU against HI and attenuates neonatal brain injury, suggesting a potential novel therapeutic agent to this disease. • FGF10 decreases neuronal death via inhibiting neuronal apoptosis • FGF10 attenuates the activation of microglia and astrocytes through modulating TLR4/NF-κB signaling pathway • FGF10 ameliorates blood-brain barrier disruption via reducing tight junction and adherens junction proteins degradation and pericytes loss • FGF10 exerts protective effects on the neurovascular unit in a rat model of neonatal HI brain injury. [ABSTRACT FROM AUTHOR]

• HMGB1 aggravates acute lung injury by suppressing immunosuppressive function of Tregs. • HMGB1 reduces the number and activity of Tregs. • HMGB1 reduces the secretion of anti-inflammatory cytokines (IL-10, TGF-β) from Tregs. • Tregs stimulated by HMGB1 regulate the macrophage polarization, as well as the proinflammatory response of macrophages. CD4+CD25+FoxP3+ T helper cells (Tregs), a subgroup of CD4+ T helper cells, are critical effectors that protect against acute lung injury (ALI) by contact-dependent suppression or releasing anti-inflammatory cytokines including interleukin-10 (IL-10), and transforming growth factor (TGF-β). HMGB1 (High mobility group box 1 protein) was identified as a nuclear non-histone DNA-binding chromosomal protein, which participates in the regulation of lung inflammatory response and pathological processes in ALI. Previous studies have suggested that Tregs overexpresses the HMGB1-recognizing receptor. However, the interaction of HMGB1 with Tregs in ALI is still unclear. To investigate whether HMGB1 aggravates ALI by suppressing immunosuppressive function of Tregs. Anti-HMGB1 antibody and recombinant mouse HMGB1 (rHMGB1) were administered in lipopolysaccharide (LPS)-induced ALI mice and polarized LPS-primed Tregs in vitro. The Tregs pre-stimulated with or without rHMGB1 were adoptively transferred to ALI mice and depleted by Diphtheria toxin (DT). For coculture experiment, isolated Tregs were first pre-stimulated with or without rHMGB1 or anti-HMGB1 antibody, then they were cocultured with bone marrow-derived macrophages (BMMs) under LPS stimulation. Tregs protected against acute lung pathological injury. HMGB1 modulated the suppressive function of Tregs as follows: reduction in the number of the cells and the activity of Tregs, the secretion of anti-inflammatory cytokines (IL-10, TGF-β) from Tregs, the production of IL-2 from CD4+ T cells and CD11c+ DCs, and the M2 polarization of macrophages, as well as inducing proinflammatory response of macrophages. HMGB1 could aggravate LPS induced-ALI through suppressing the activity and function of Tregs. [ABSTRACT FROM AUTHOR]