Dynamic human exposure to airborne bacteria-associated antibiotic resistomes revealed by longitudinal personal monitoring data.

Airborne antibiotic-resistant bacteria (ARB) can critically impact human health. We performed resistome profiling of 283 personal airborne exposure samples from 15 participants spanning 890 days and 66 locations. We found a greater diversity and abundance of airborne bacteria community and antibiotic resistomes in spring than in winter, and temperature contributed largely to the difference. A total of 1123 bacterial genera were detected, with 16 genera dominating. Of which, 7/16 were annotated as major antibiotic resistance gene (ARG) hosts. The participants were exposed to a highly dynamic collection of ARGs, including 322 subtypes conferring resistance to 18 antibiotic classes dominated by multidrug, macrolide-lincosamide-streptogramin, ß-lactam, and fosfomycin. Unlike the overall community-level bacteria exposure, an extremely high abundance of specific ARG subtypes, including lunA and qacG, were found in some samples. Staphylococcus was the predominant genus in the bacterial community, serving as a primary bacterial host for the ARGs. The annotation of ARG-carrying contigs indicated that humans and companion animals were major reservoirs for ARG-carrying Staphylococcus. This study contextualized airborne antibiotic resistomes in the precision medicine framework through longitudinal personal monitoring, which can have broad implications for human health.

Safety and immunogenicity of a bivalent HPV16/18 vaccine in Chinese females.

As global supply is still inadequate to address the worldwide requirements for HPV vaccines, we assessed the safety and immunogenicity of a new bivalent HPV16/18 vaccine. In this randomized, double-blind, placebo-controlled, phase 2 trial, healthy 9-45-year-old Chinese females in three age cohorts (600 aged 9-17 years; 240 aged 18-26 years; 360 aged 27-45 years) were randomized 1:1 to receive three doses (0,2,6 months) of HPV16/18 vaccine or placebo. We measured neutralizing antibodies against HPV 16 and 18 at 7 months and monitored safety to 12 months in all age cohorts; 9-17-year-old girls were monitored for safety and immunogenicity to 48 months. In vaccinees, 99.8% seroconverted for HPV 16 and 18 types at 7 months; respective GMTs of 5827 (95% CI: 5249, 6468) and 4223 (3785, 4713) were significantly (p < .001) higher than controls for all comparisons. GMTs in the 9-17-year-olds, which were significantly higher than in older women at 7 months, gradually declined to 48 months but remained higher than placebo with seropositivity rates maintained at 98.5% and 97.6% against HPV 16 and 18, respectively. Adverse events occurred at similar rates after vaccine and placebo (69.8% vs. 72.5%, p = .308), including solicited local reactions and systemic adverse events which were mainly mild-to-moderate. The bivalent HPV16/18 vaccine was well tolerated and induced high levels of neutralizing antibodies in all age groups which persisted at high levels to 48 months in the 9-17-year-old age group which would be the target for HPV vaccination campaigns.

Safety and immunogenicity of a pichia pastoris-expressed bivalent human papillomavirus (types 16 and 18) L1 virus-like particle vaccine in healthy Chinese women aged 9-45 years: A randomized, double-blind, placebo-controlled phase 1 clinical trial.

BACKGROUND: We evaluated the safety and immunogenicity of high and low doses of a novel pichia pastoris-expressed bivalent (types 16 and 18) human papillomavirus (HPV) virus-like particle vaccine. METHODS: In this randomized, double-blind, placebo-controlled phase 1 trial, we enrolled 160 healthy females aged 9-45 years in Guangxi, China who were randomized (1:1:2) to receive either low (0.5 mL) or high (1.0 mL) dosages of bivalent HPV vaccine, or placebo (aluminum adjuvant) in a 0, 2, 6 months schedule. Adverse events and other significant conditions that occurred within 30 days after each vaccination were recorded throughout the trial. Sera were collected at days 0, 60, 180 and 210 to measure anti-HPV 16/18 neutralizing antibodies. RESULTS: A total of 160 participants received at least one dose of the HPV vaccine and 152 completed the three dose vaccination series. Reporting rates of adverse events in placebo, low dose (0.5 mL) and high dose (1.0 mL) groups were 47.5 %, 55.0 % and 55.0 %, respectively. No serious adverse events occurred during this trial. 100 % of the participants who received three doses of the HPV vaccine produced neutralizing antibodies against HPV 16/18 vaccine. For HPV 16 and HPV 18, the geometric mean titers (GMTs) were similar between the low dose group (GMTHPV 16 = 10816 [95 % CI: 7824-14953]), GMTHPV 18 = 3966 [95 % CI: 2693-5841]) and high dose group (GMT HPV 16 = 14482 [95 % CI: 10848-19333], GMT HPV 18 = 3428 [95 % CI: 2533-4639]). CONCLUSION: The pichia pastoris-expressed bivalent HPV vaccine was safe and immunogenic in Chinese females aged 9-45 years. The low dosage (0.5 mL) was selected for further immunogenicity and efficacy study.

Current-Induced Spin Photocurrent in GaAs at Room Temperature.

Circularly polarized photocurrent, observed in p-doped bulk GaAs, varies nonlinearly with the applied bias voltage at room temperature. It has been explored that this phenomenon arises from the current-induced spin polarization in GaAs. In addition, we found that the current-induced spin polarization direction of p-doped bulk GaAs grown in the (001) direction lies in the sample plane and is perpendicular to the applied electric field, which is the same as that in GaAs quantum well. This research indicates that circularly polarized photocurrent is a new optical approach to investigate the current-induced spin polarization at room temperature.

Dietary Acid Load and the Risk of Pancreatic Cancer: A Prospective Cohort Study.

BACKGROUND: Modern Western diets are rich in acidogenic foods. Human and in vitro studies suggest a potential link between dietary acid load and cancer risk. However, no epidemiologic studies have investigated the association of dietary acid load with the risk of pancreatic cancer. Therefore, we conducted a prospective cohort study to fill this gap. METHODS: A population-based cohort of 95,708 American adults was identified. Potential renal acid load (PRAL) and net endogenous acid production (NEAP) were used to assess dietary acid load of each subject, with greater values indicating greater dietary acid load. Cox regression was used to estimate risk estimates for pancreatic cancer incidence. Predefined subgroup analysis was used to identify the potential effect modifiers. RESULTS: A total of 337 pancreatic cancer cases were observed during 848,534.0 person-years of follow-up. PRAL score was found to be positively associated with the risk of pancreatic cancer [fully adjusted HRquartile 4 vs. 1: 1.73; 95% confidence interval (95% CI), 1.21-2.48; P trend = 0.001] in a nonlinear dose-response pattern (P nonlinearity = 0.012). Subgroup analysis found that the positive association of PRAL score with the risk of pancreatic cancer was more pronounced in subjects aged <65 years than in those ≥65 years (P interaction = 0.018). Similar results were obtained for NEAP score. CONCLUSIONS: Higher dietary acid load is associated with a higher risk of pancreatic cancer. Future studies should validate our findings in other populations and settings. IMPACTS: This is the first epidemiologic study suggesting that reducing dietary acid load may be useful in primary prevention of pancreatic cancer.

Overexpression of Rab40b Promotes Hepatocellular Carcinoma Cell Proliferation and Metastasis via PI3K/AKT Signaling Pathway.

BACKGROUND: Rab40b is an evolutionarily conserved Rab GTPase that plays an important role in intracellular trafficking and is closely related to cancer progression. However, the role and potential molecular mechanism of Rab40b in hepatocellular carcinoma (HCC) have not yet been elucidated. MATERIALS AND METHODS: The expression of Rab40b in HCC tissues and peritumour tissues was tested by qRT-PCR, Western blotting and histological analysis. A Kaplan-Meier survival curve was generated based on the expression of Rab40b in the HCC samples. Cell proliferation assays, wound healing assays, and transwell assays are used to examine the effect of Rab40b on HCC cell growth in vitro. The effect of Rab40b on cell cycle was examined by flow cytometry. A xenograft implantation model was used to assess the effect of Rab40b on the development of HCC cells in vivo. RESULTS: Rab40b protein expression is upregulated in HCC tissues, and this upregulation is associated with high pathological stage and poor prognosis in HCC patients. Rab40b overexpression promotes the proliferation and metastasis of HCC cells by upregulating cyclin D1, cyclin E1 and matrix metalloproteinase 2 (MMP2) through the PI3K/AKT signalling pathway. Conversely, Rab40b inhibitors can significantly inhibit the proliferation and metastasis of HCC cell lines and induce G0/G1 cell cycle arrest and apoptosis. Studies of a nude mouse xenograft model demonstrated that Rab40b knockdown can significantly inhibit the proliferation and progression of HCC tumours in vivo. CONCLUSION: Overall, this study demonstrates that Rab40b is an important oncoprotein that promotes HCC progression by regulating the expression of cyclin D1, cyclin E1, p21 and MMP2 through the PI3K/AKT signalling pathway.

Sheng Mai San protects H9C2 cells against hyperglycemia-induced apoptosis.

BACKGROUND: Sheng Mai San (SMS) has been proven to exhibit cardio-protective effects. This study aimed to explore the molecular mechanisms of SMS on hyperglycaemia (HG)-induced apoptosis in H9C2 cells. METHODS: HG-induced H9C2 cells were established as the experimental model, and then treated with SMS at 25, 50, and 100 µg/mL. H9C2 cell viability and apoptosis were quantified using MTT and Annexin V-FITC assays, respectively. Furthermore, Bcl-2/Bax signalling pathway protein expression and Fas and FasL gene expression levels were quantified using western blotting and RT-PCR, respectively. RESULTS: SMS treatments at 25, 50, 100 µg/mL significantly improved H9C2 cell viability and inhibited H9C2 cell apoptosis (p < 0.05). Compared to the HG group, SMS treatment at 25, 50, and 100 µg/mL significantly downregulated p53 and Bax expression and upregulated Bcl-2 expression (p < 0.05). Moreover, SMS treatment at 100 µg/mL significantly downregulated Fas and FasL expression level (p < 0.05) when compared to the HG group. CONCLUSION: SMS protects H9C2 cells from HG-induced apoptosis probably by downregulating p53 expression and upregulating the Bcl-2/Bax ratio. It may also be associated with the inhibition of the Fas/FasL signalling pathway.

[Effect of Electroacupuncture and Manual Acupuncture on Colonic Inflammatory Injury, Cytokine Levels and Cell Apoptosis in Ulcerative Colitis Rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) and manual acupuncture interventions on colonic inflammatory injury, cytokine level and cell apoptosis in ulcerative colitis (UC)rats, so as to reveal its mechanisms underlying improvement of UC. METHODS: A total of 32 SD rats were randomized into control, model, EA and manual acupuncture groups (8 rats/group). The UC model was established by intrarectally administration of 5% trinitro-benzene-sulfonic acid (TNBS)+ dehydrated alcohol. Both "Quchi" (LI 11) and "Zusanli" (ST 36) were punctured with filiform needles for 20 min in the manual acupuncture group or stimulated with EA (8 Hz/25 Hz, 2-4 mA, and duration of 20 min) in the EA group. The treatment was conducted once daily for consecutive 6 days. Changes of body weight and pathological state of colitis were observed. The contents of pro-inflammatory cytokines (TNF-α, IL-1 ß, IL-6), anti-inflammatory cytokine (IL-10), homocysteine (Hcy) and myeloperoxidase (MPO, two oxygen free radicals associated substances) in the colon tissues were detected by ELISA, and the protein expression levels of Bcl-2,Bax,phosphorylated (p)-inhibitor of nuclear factor kappaB kinase α(IκBα) and p-p 65 (a subunit of nuclear factor) of colonic tissues were detected by Western blot, separately. RESULTS: Compared with the control group, the body weight was decreased and the state of the swelling and hemorrhage of the colon got worsened in the model group, while the state of the swelling and hemorrhage of the colon was better in both EA and manual acupuncture groups, and the body weight was clearly increased from day 4 on in both treatment groups. The concentrations of colonic TNF-α, IL-1 ß, IL-6, IL-10, MPO and Hcy were all significantly higher in the model group than in the control group (P<0.01), but those of colonic TNF-α, IL-1 ß, IL-6 in both EA and manual acupuncture groups, those of MPO and Hcy in the EA group were significantly down-regulated following the intervention (P<0.05, P<0.01), and that of IL-10 was notably further increased in the manual acupuncture group (P<0.05). In addition, modeling-induced remarkable down-regulation of colonic Bcl-2/Bax, and marked up-regulation of expression of IκBα and p-p 65 proteins were significantly suppressed in both EA and manual acupuncture groups (P<0.01). CONCLUSIONS: Both EA and manual acupuncture interventions Feb alleviate the colonic lesions in UC rats, which Feb be related to their functions in regulating levels of pro-inflammatory and anti-inflammatory cytokines, in balancing the expression of apoptosis-related protein and anti-apoptosis-related protein and in down-regulating the expression of the key nuclear transcription factors in the colonic tissue.

[Distribution and expression of TGF-ß2 in the capsule of children with developmental dysplasia of the hip].

OBJECTIVE: This study examined the distribution and expression of transforming growth factor-ß2 (TGF-ß2) in the hip capsule of children with developmental dysplasia (dislocation) of the hip (DDH) and non-DDH children in order to investigate the roles of TGF-ß2 in hip joint laxity. METHODS: Eight children with DDH and eight age- and gender-matched non-DDH children (control group) were enrolled. The immunohistochemical technique (S-P method) was used to examine the distribution and content of TGF-ß2 in the hip capsule. Semiquantitative RT-PCR method was used to detect mRNA expression of TGF-ß2 in the hip capsule. The quantitative analysis of TGF-ß2 was performed by professional image software. RESULTS: A high expression of TGF-ß2 was observed in the synovial layer with fibroblast regularly arranged parallel to the joint surface. There was decreased expression of TGF-ß2 in the fibrous layer of the capsule. The percentage of positive fibroblasts and the gray-scale density in the fibrous layer in the DDH group were significantly lower than those in the control group (P < 0.01). TGF-ß2 mRNA expression in the DDH group decreased compared with that in the control group (P < 0.05). CONCLUSIONS: The decreased TGF-ß2 in distribution, content and mRNA expression in the hip capsule might contribute to hip joint laxity in children with DDH.

[Expression of COL1a1 and COL3a1 in the capsule of children with developmental dislocation of the hip].

OBJECTIVE: The etiology of developmental dislocation of the hip (DDH) remains uncertain, but some research has shown that this disorder is closely related to hip joint laxity. This study examined the expression of collagens type I and III mRNA and protein in the hip capsule of children with DDH in order to investigate the roles of collagens type I and III in hip joint laxity. METHODS: Nine children with DDH and nine age and gender-matched normal children (control group) were enrolled. Semiquantitative RT-PCR method was used to detect mRNA expression of COL1a1 and COL3a1 in the hip capsule. Western-Blot method was used to detect protein expression of COL1a1 and COL3a1 in the hip capsule. The quantitative analysis of the COL1a1 and COL3a1 was performed by professional image software and the results were analyzed with standard statistical methods. RESULTS: mRNA and protein expression of COL1a1 in the DDH group was significantly lower than that in the control group (P<0.01). Compared with the control group, COL1a3 mRNA expression in the DDH group decreased significantly (P<0.01), but COL1a3 protein expression was not significantly different. CONCLUSIONS: The decreased collagen I mRNA and protein expression in the hip capsule might contribute to hip joint laxity in children with DDH. Collagen type III may not be associated with hip joint laxity in DDH.

[Appropriate soil nitrate N content for a winter wheat/summer maize rotation system in North China Plain].

A field experiment with 12-level N fertilization in winter wheat growth season and zero-N in summer maize growth season was conducted to study the appropriate soil nitrate N content for a winter wheat/summer maize rotation system in North China Plain. The results showed that when the soil mineral N content before sowing was higher, a split application of 150 kg N x hm(-2) in winter wheat growth season could meet the N demand of both winter wheat and summer maize in the rotation system. The N use efficiency of winter wheat in different N treatments was only from 11% to 23%, while the residual N use efficiency of summer maize ranged from 30% to 52%. When the nitrate N content in top 90 cm soil layer before maize sowing was up to 82 and 151 kg x hm(-2), respectively, the N demand of summer maize at its ten-leaf stage and in its whole growth season could be met with no N application. However, when the nitrate N content in top 90 cm soil layer was less than 46 and 65 kg x hm(-2) at maize ten-leaf stage and after harvest, respectively, no N application could impact maize growth, and decrease its grain yield. With the maize yield and environmental protection considered comprehensively, the nitrate N content in top 90 cm soil layer should be maintained at an appropriate level from 65 to 151 kg x hm(-2) during maize growth season.

[Studies on the mechanism of Cr-induced DNA damage in glouse].

OBJECTIVE: To investigate the mechanism of Cr-induced DNA damage in glouse. METHODS: The studies were conducted at three pH values(pH 6.5, 7.5, 8.5) with a range of sugars, including D-glucose, alpha-methyl-D-glucose, 2-deoxy-D-glucose, and D-glucose-C-d7. DNA damage was analyzed by gel electrophoresis, and the new species and their lifetime were detected by EPR. RESULTS: The results of these experiments have reinforced the postulate that Cr (V) complexes are likely to be involved in the genotoxic damage that eventually results in Cr-induced cancers. With an increase in the pH values, the amount of Form II DNA decreased due to the increasing rate of Cr (V) disproportionation and H concentration. On the other hand, the presence of sugars in the reaction system generated Cr-mixed-ligand complexes, which could also cause DNA cleavage. CONCLUSION: Proposed mechanism of DNA cleavage are presented induced by Cr (V)-mixed-ligand.