Tailoring the growth route of lithium peroxide through the rational design of a sodium-doped nickel phosphate catalyst for lithium-oxygen batteries.

Tailoring the morphology and structure of Li2O2, the discharge product of lithium-oxygen batteries (LOBs), through the rational design of cathode catalysts is an efficient strategy to promote the electrochemical performance of LOBs. In this work, sodium-doped nickel phosphate nanorods (Na-NiPO NRs) grown on Ni foam (NF) were prepared by the hydrothermal method and subsequent calcination. For the Na-NiPO NRs, the electronic structure could be optimized and abundant void space among the nanorods would provide abundant transport channels. Adopted as the cathodes, the Na-NiPO NRs could facilitate the uniform growth of sea cucumber-like Li2O2 with sufficient Li2O2-electrolyte and Li2O2-catalyst interfaces, significantly promoting the charge process. Therefore, LOBs could deliver a high discharge capacity of 10365.0 mA h g-1 at 100 mA g-1. And a low potential gap of 1.16 V can be achieved at 200 mA g-1 with a capacity of 500 mA h g-1. The proposed strategy demonstrates the role of the morphology and electronic structure of the cathode catalysts in tuning the Li2O2 morphology and provides a novel approach for achieving high-performance LOBs.

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.

Safety of 9-valent human papillomavirus vaccine administered to males and females in routine use.

BACKGROUND: The nine-valent human papillomavirus vaccine (HPV9, Gardasil®9) was licensed in the USA in December 2014. This study was a multiyear post-licensure study to assess HPV9 safety following routine administration. METHODS: This retrospective cohort study compared the risk of emergency department visits and hospitalizations during the interval soon after vaccination with risk during a later interval. Kaiser Permanente Northern California (KPNC) members aged ≥ 9 years who received ≥ 1 HPV9 dose between 10/1/2015-9/30/2017 were included. Outcomes were grouped into predefined diagnostic categories. We compared the odds of events in postvaccination risk intervals (days 0-14, days 1-60) with odds of events during control intervals (days 61-75, days 61-120) using conditional logistic regression. We characterized prespecified events on the day of vaccination (allergic reaction and syncope) and all deaths in the study period. RESULTS: The study included 215,965 individuals receiving ≥ 1 dose of HPV9, of whom 140,628 had no prior HPV vaccination. We observed similar numbers of males and females and racial/ethnic diversity consistent with the underlying population. At first dose median age was 12-13 years and 77% received ≥ 1 concomitant vaccine. Eighteen event categories were significantly elevated, including skin disorders (odds ratio [OR] 1.88, 95% confidence interval [CI] 1.00, 3.53) and ill-defined conditions (OR 1.36, 95% CI 1.13, 1.64; category includes abdominal pain, allergic reactions, syncope, etc.). On review, most findings were previously known, preceded vaccination, or had other causes. Allergic reactions and syncope at vaccination were infrequent but many were potentially related. No deaths (n = 37) were considered related to HPV9 and were consistent with the background rate. CONCLUSIONS: We did not identify new safety concerns related to HPV9. The results are consistent with the HPV9 safety profile as established from previous studies/surveillance. REGISTRATION: European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (EUPAS13151, protocol V503-028).

Human papillomavirus seroprevalence and seroconversion following baseline detection of nine human papillomavirus types in young women.

BACKGROUND: Estimates of the humoral immune response to incident human papillomavirus (HPV) infections are limited. METHODS: In this post hoc analysis of 3875 women aged 16-23 years from a 4-valent HPV vaccine trial (NCT00092482), HPV seroprevalence on day 1 was measured with a 9-valent HPV (HPV 6/11/16/18/31/33/45/52/58) competitive Luminex immunoassay and compared with cervical/external genital HPV detection by polymerase chain reaction. In the control group, among women who were HPV DNA‒negative on day 1, seroconversion following initial HPV detection was estimated using Kaplan-Meier methods. RESULTS: Type-specific HPV seropositivity among women with no day 1 cervical/external genital HPV detection was 0.6%-3.6%. Women with any 9-valent HPV (9vHPV) cervical/external genital detection (796/3875; 20.5%) had concordant seropositivity ranging from 13.4% (HPV 45) to 38.5% (HPV 6). Among women in the control group who were negative for all HPV types on day 1, seroconversion by month 30 after initial detection ranged from 29% (HPV 45) to 75% (HPV 16). CONCLUSIONS: Humoral immune response to HPV is variable and dynamic, depending on type-specific exposure. This longitudinal analysis provides insight into the relationship between incident infection and seropositivity. CLINICALTRIALS: gov; NCT00092482 https://clinicaltrials.gov/ct2/show/NCT00092482.

Acute 1-NP exposure induces inflammatory responses through activating various inflammatory signaling pathways in mouse lungs and human A549 cells.

1-Nitropyrene (1-NP), a key component of fine particulate matter (PM2.5), is a representative of nitrated polycyclic aromatic hydrocarbons (NPAHs). The aim of this research is to investigate proinflammatory effects of acute 1-NP exposure in mouse lungs and human A549 cells. All mice except controls were intratracheally instilled with 1-NP (20 µg/mouse). A549 cell, a human lung cancer cell line, was cultured with or without 1-NP (5 µM). Acute 1-NP exposure elevated lung weight and caused infiltration of inflammatory cells, especially neutrophils in mouse lungs. Although it had little effect on serum TNF-α and KC, acute 1-NP exposure elevated the levels of TNF-α and KC in BALF. Correspondingly, acute 1-NP exposure upregulated pulmonary Il-1ß, Il-6, Tnf-α and Kc. Mechanistically, acute 1-NP exposure activated nuclear factor kappa B (NF-κB) in mouse lungs and human A549 cells. Additionally, acute 1-NP exposure induced Akt phosphorylation in mouse lungs and human A549 cells. Moreover, acute 1-NP exposure induced phosphorylation of pulmonary JNK and ERK1/2, molecules of the mitogen-activated protein kinase (MAPK) pathway. This study provides evidence that acute 1-NP exposure induces inflammatory responses through activating various inflammatory signaling pathways in mouse lungs and human A549 cells.

Vitamin D deficiency exacerbates bleomycin-induced pulmonary fibrosis partially through aggravating TGF-ß/Smad2/3-mediated epithelial-mesenchymal transition.

BACKGROUND: Our earlier report indicated that active vitamin D3 inhibited epithelial-mesenchymal transition (EMT) in bleomycin (BLM)-induced pulmonary fibrosis. The objective of this study was to further investigate whether vitamin D deficiency exacerbates BLM-induced pulmonary fibrosis. METHODS: This study consists of two independent experiments. Experiment 1, male mice were fed with vitamin D deficient (VDD) fodder. Experiment 2, Cyp27b1+/+, Cyp27b1+/- and Cyp27b1-/- mice were fed with standard diet. For pulmonary fibrosis, mice were intratracheally instilled with a single dose of BLM (1.5 mg/kg). Serum 25(OH) D level was measured. Pulmonary collagen deposition was assessed by Sirius red staining. EMT was measured and transforming growth factor-beta (TGF-ß)/Smad3 signaling was evaluated in the lungs of BLM-treated mice. RESULTS: The relative weight of lungs was elevated in BLM-treated mice. Col1α1 and Col1α2, two collagen protein genes, were upregulated, and collagen deposition, as determined by Sirius red staining, was observed in the lungs of BLM-treated mice. E-cadherin, an epithelial marker, was downregulated. By contrast, vimentin and α-SMA, two EMT markers, were upregulated in the lungs of BLM-treated mice. Pulmonary TGF-ß/Smad3 signaling was activated in BLM-induced lung fibrosis. Further analysis showed that feeding VDD diet, leading to vitamin D deficiency, aggravated elevation of BLM-induced relative lung weight. Moreover, feeding VDD diet aggravated BLM-induced TGF-ß/Smad3 activation and subsequent EMT in the lungs. In addition, feeding VDD diet exacerbated BLM-induced pulmonary fibrosis. Additional experiment showed that Cyp27b1 gene knockout, leading to active vitamin D3 deficiency, exacerbated BLM-induced pulmonary fibrosis. Moreover, Cyp27b1 gene knockout aggravated pulmonary TGF-ß/Smad2/3 activation and subsequent EMT in BLM-induced lung fibrosis. CONCLUSION: Vitamin D deficiency exacerbates BLM-induced pulmonary fibrosis partially through aggravating TGF-ß/Smad2/3-mediated EMT in the lungs.

Candida albicans-induced acute lung injury through activating several inflammatory signaling pathways in mice.

Candida albicans infection-induced acute lung injury is one of the most prevalent diseases in immunosuppressive individual. Nevertheless, the mechanism by which Candida albicans induced acute lung injury remains unclear. The present study investigated the mechanism by which Candida albicans induced acute lung injury in mice. Mice were randomly divided into four groups and intratracheally injected with 60 µl Candida albicans (106 CFU) or normal saline. Half of the mice were sacrificed at 6 h after Candida albicans. The rest of the mice for survival test were observed until 7 d after Candida albicans. As expected, immunosuppression aggravated Candida albicans-induced acute lung injury and death in mice. Additionally, Candida albicans infection elevated mRNA levels of pro-inflammatory and chemokines in lungs and the levels of IL-6, IL-1ß and IL-17 in serum. Further study showed that Candida albicans promoted nuclear translocation of NF-κB p50 and p65 subunits in pulmonary epithelial cells and interstitial cells. Candida albicans induced pulmonary p38, ERK1/2 and Akt phosphorylation in normal and immunosuppressive mice. Moreover, Candida albicans infection activated pulmonary STAT3 signaling in normal and immunosuppressive mice. Overall, these results suggest that Candida albicans induced acute lung injury and death may be through activating several inflammatory signaling pathways.

Human Papillomavirus Genotypes From Vaginal and Vulvar Intraepithelial Neoplasia in Females 15-26 Years of Age.

OBJECTIVE: To estimate the proportion of vulvar and vaginal low-grade and high-grade squamous intraepithelial lesions (LSILs and HSILs) in females 15-26 years of age attributable to 14 human papillomavirus (HPV) genotypes (6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59). METHODS: A post hoc analysis of prospectively diagnosed vulvar and vaginal LSILs and HSILs among females 15-26 years of age enrolled in the placebo arms of two phase 3, randomized HPV vaccine trials assessed 14 prespecified HPV genotypes associated with cervical cancers or anogenital warts using a type-specific multiplex polymerase chain reaction assay. The frequency of lesions associated with specific HPV genotypes was estimated by proportional and other attribution methods. RESULTS: During approximately 4 years of follow-up in 8,798 females, 40 vulvar LSILs and 46 vulvar HSILs were diagnosed in 68 females, and 118 vaginal LSILs and 33 vaginal HSILs were diagnosed in 107 females. Females developing vulvar (41.2%) or vaginal (49.5%) lesions also had cervical lesions, whereas 6.5% of females with cervical lesions had vaginal or vulvar lesions. At least 1 of the 14 HPV genotypes was detected in females with vulvar LSIL (72.5%), vulvar HSIL (91.3%), vaginal LSIL (61.9%), and vaginal HSIL (72.7%). Considering only HPV-positive lesions, the nine most common genotypes causing cervical cancer and anogenital warts (6, 11, 16, 18, 31, 33, 45, 52, and 58) were found in 89.4% of vulvar LSILs, 100% of vulvar HSILs, 56.0% of vaginal LSILs, and 78.3% of vaginal HSILs. CONCLUSION: Most vulvar and vaginal lesions were attributable to at least 1 of the 14 HPV genotypes analyzed. Effective immunization programs could potentially prevent substantial numbers of HPV-related vulvar and vaginal LSILs and HSILs. CLINICAL TRIAL REGISTRATION: CLINICALTRIALS.GOV,: NCT00092521 and NCT00092534.

Depressive symptoms and risk of uterine leiomyomata.

OBJECTIVE: Uterine leiomyomata (UL) are a major source of gynecologic morbidity and the primary indication for hysterectomy. Depression can cause dysregulation of the hypothalamic-pituitary-adrenal axis, which may affect the synthesis of reproductive hormones involved in UL pathogenesis. We assessed the association between depressive symptoms and UL among 15,963 premenopausal women. STUDY DESIGN: Data were derived from the Black Women's Health Study, a prospective cohort study. In 1999 and 2005, the Center for Epidemiologic Studies Depression Scale (CES-D) was used to ascertain depressive symptoms. On biennial follow-up questionnaires from 1999 through 2011, women reported physician-diagnosed depression, antidepressant use, and UL diagnoses. Incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox regression. RESULTS: There were 4722 incident UL cases diagnosed by ultrasound (n=3793) or surgery (n=929) during 131,262 person-years of follow-up. Relative to baseline CES-D scores<16, IRRs were 1.05 (95% CI, 0.98-1.13) for CES-D scores 16-24 and 1.16 (95% CI, 1.06-1.27) for CES-D scores≥25 (P-trend=.001). IRRs for current and past physician-diagnosed depression relative to no depression were 1.15 (95% CI, 0.98-1.34) and 1.25 (95% CI, 1.13-1.39), respectively. Results persisted after further control for antidepressant use. IRRs for current and past use of antidepressants (any indication) relative to never use were 1.11 (95% CI, 0.97-1.28) and 1.32 (95% CI, 1.14-1.52), respectively. CONCLUSION: In this cohort of black women, greater depressive symptoms were associated with UL, independent of antidepressant use, supporting the hypothesis that dysregulation of the hypothalamic-pituitary-adrenal axis increases UL risk.

Age at natural menopause in relation to all-cause and cause-specific mortality in a follow-up study of US black women.

OBJECTIVES: Early age at natural menopause has been associated with increased all-cause mortality in several studies, although the literature is not consistent. This relation has not been examined among African American women. STUDY DESIGN: Data were from the Black Women's Health Study, a follow-up study of African-American women enrolled in 1995. Among 11,212 women who were naturally menopausal at entry to the study or during follow-up through 2008, we assessed the relation of age at natural menopause to all-cause and cause-specific mortality. At baseline and biennially, participants reported on reproductive and medical history, including gynecologic surgeries and exogenous hormone use. Mortality data were obtained from the National Death Index. Multivariable Cox proportional hazard models were used to estimate mortality rate ratios (MRR) and 95% confidence intervals (CI) for categories of age at menopause. RESULTS: Of 692 deaths identified during 91,829 person years of follow-up, 261 were due to cancer, 199 to cardiovascular diseases and 232 to other causes. Natural menopause before age 40 was associated with increased all-cause mortality (MRR=1.34, 95% CI 0.96-1.84, relative to menopause at 50-54 years; P-trend=0.04) and with the subcategories of death considered - cancer, cardiovascular disease, and all other causes. The associations were present among never and ever users of postmenopausal female hormones and among never and ever smokers. CONCLUSIONS: In this large prospective cohort of African-American women, natural menopause before age 40 was associated with a higher rate of all-cause and cause-specific mortality. These findings provide support for the theory that natural menopause before age 40 may be a marker of accelerated somatic aging.

A novel prophenoloxidase 2 exists in shrimp hemocytes.

The prophenoloxidase (proPO)-activating system in crustaceans and other arthropods is regarded as a constituent of the immune system and plays an important role in defense against pathogens. Hitherto in crustaceans, only one proPO gene per species has been identified. Here we report the identification of a novel proPO-2 (LvproPO-2) from the hemocytes of Litopenaeus vannamei, which shows 72% identity to proPO-1 (LvproPO-1) cloned previously. Northern blotting analysis and quantitative real-time PCR reveal that LvproPO-2 is mainly expressed in the hemocytes, and its expression is down-regulated in shrimp challenged with white spot syndrome virus (WSSV). Western blotting analysis shows that most LvproPO-2/LvPO-2 (L. vannamei phenoloxidase-2) exists in the hemocytes, but not in plasma of L. vannamei. LvproPO-2/LvPO-2 could be detected on the hemocyte surface and the nucleus of hemocytes by indirect immunofluorescence assay (IFA). These findings provide insight into the molecular biological basis for further studying on the defense mechanism of shrimp innate immunity, especially on the proPO-activating system and melanization cascade of shrimp.

A novel C-type lectin from the shrimp Litopenaeus vannamei possesses anti-white spot syndrome virus activity.

C-type lectins play key roles in pathogen recognition, innate immunity, and cell-cell interactions. Here, we report a new C-type lectin (C-type lectin 1) from the shrimp Litopenaeus vannamei (LvCTL1), which has activity against the white spot syndrome virus (WSSV). LvCTL1 is a 156-residue polypeptide containing a C-type carbohydrate recognition domain with an EPN (Glu(99)-Pro(100)-Asn(101)) motif that has a predicted ligand binding specificity for mannose. Reverse transcription-PCR analysis revealed that LvCTL1 mRNA was specifically expressed in the hepatopancreas of L. vannamei. Recombinant LvCTL1 (rLvCTL1) had hemagglutinating activity and ligand binding specificity for mannose and glucose. rLvCTL1 also had a strong affinity for WSSV and interacted with several envelope proteins of WSSV. Furthermore, we showed that the binding of rLvCTL1 to WSSV could protect shrimps from viral infection and prolong the survival of shrimps against WSSV infection. Our results suggest that LvCTL1 is a mannose-binding C-type lectin that binds to envelope proteins of WSSV to exert its antiviral activity. To our knowledge, this is the first report of a shrimp C-type lectin that has direct anti-WSSV activity.

Characterization of a prophenoloxidase from hemocytes of the shrimp Litopenaeus vannamei that is down-regulated by white spot syndrome virus.

Previously, a prophenoloxidase (proPO) gene (named proPO-a here) from hemocytes of Litopenaeus vannamei was isolated. Here, a proPO-b gene was also identified and characterized from hemocytes of L. vannamei. The cDNA sequences of proPO-a and proPO-b were compared, and it was found that both proPOs had a microsatellite DNA site near the 3' end of the open reading frame (ORF). However, the microsatellite DNA of proPO-b contained a compound imperfect simple sequence repeats (SSR) ((CT)(38)(CA)(8)(AA)(CA)(3)(TA)(CA)(14)), which was different from the perfect one ((CT)(20)) of proPO-a, and the cDNA sequences of proPO-a and proPO-b prior to the microsatellite DNA were almost identical, but differed after the microsatellite DNA. ProPO-b (3232 bp) was longer than proPO-a (2471 bp). The 3' UTR sequence after SSR of proPO-a was not detected in shrimp randomly collected from five different geographically separate populations by reverse-transcription polymerase chain reaction (RT-PCR). On the contrary, the 3' UTR sequence of proPO-b was detected in all five groups of shrimps. Northern blot analysis showed that a transcript at approximately 3.2kb, but not 2.5kb, was detected mainly in hemocytes, and also present in midgut, gill, heart, stomach, posterior midgut cecum, and cuticular epidermis, but no signal was detected in hepatopancreas and musculature. RT-PCR and quantitative real-time RT-PCR analysis showed similar results of the proPO-b expression profile in these shrimp tissues. We also observed that proPO-b expression was down-regulated in shrimp challenged with white spot syndrome virus (WSSV). Our results suggest that proPO-b is a main transcript form of proPO gene in L. vannamei, and it may play a role in defence against WSSV virus.