The development of high-efficiency and low-cost catalysts for hydrogen release from chemical hydrogen-storage materials is essential for the hydrogen-economy paradigm. Herein, we report a facile and ...controllable method to fabricate a series of Co-doped nickel phosphides and their corresponding nanohybrids with graphene oxide (GO) as highly efficient, robust and noble-metal-free catalysts for ammonia borane hydrolysis. The incorporation of Co into Ni 2 P effectively optimizes the electronic structures of Ni 2−x Co x P catalysts to enhance their interaction with AB and simultaneously facilitate the hydroxyl activation of AB, resulting in the reduction of the reaction energy barrier and thus substantial improvement of the catalytic rate.
Abstract
Background
The high cost and insufficient supply of human papillomavirus (HPV) vaccines have slowed the pace of controlling cervical cancer. A phase III clinical trial was conducted to ...evaluate the efficacy, safety, and immunogenicity of a novel Escherichia coli-produced bivalent HPV-16/18 vaccine.
Methods
A multicenter, randomized, double-blind trial started on November 22, 2012 in China. In total, 7372 eligible women aged 18–45 years were age-stratified and randomly assigned to receive three doses of the test or control (hepatitis E) vaccine at months 0, 1, and 6. Co-primary endpoints included high-grade genital lesions and persistent infection (over 6 months) associated with HPV-16/18. The primary analysis was performed on a per-protocol susceptible population of individuals who were negative for relevant HPV type-specific neutralizing antibodies (at day 0) and DNA (at day 0 through month 7) and who received three doses of the vaccine. This report presents data from a prespecified interim analysis used for regulatory submission.
Results
In the per-protocol cohort, the efficacies against high-grade genital lesions and persistent infection were 100.0% (95% confidence interval = 55.6% to 100.0%, 0 of 3306 in the vaccine group vs 10 of 3296 in the control group) and 97.8% (95% confidence interval = 87.1% to 99.9%, 1 of 3240 vs 45 of 3246), respectively. The side effects were mild. No vaccine-related serious adverse events were noted. Robust antibody responses for both types were induced and persisted for at least 42 months.
Conclusions
The E coli-produced HPV-16/18 vaccine is well tolerated and highly efficacious against HPV-16/18–associated high-grade genital lesions and persistent infection in women.
Three new polyketides, eutyketides A and B (1 and 2) and cytosporin X (3), along with four known compounds (4–7), were obtained from the marine-derived fungus Eutypella scoparia. The planar ...structures of 1 and 2 were elucidated by extensive HRMS and 1D and 2D NMR analyses. Their relative configurations of C-13 and C-14 were determined with chemical conversions by introducing an acetonylidene group. The absolute configurations of 1–3 were determined by comparing their experimental electronic circular dichroism (ECD) data with their computed ECD results. All of the isolated compounds were tested for their anti-inflammatory activities on lipopolysaccharide-induced nitric oxide production in RAW 264.7 macrophages. Compounds 5 and 6 showed stronger anti-inflammatory activities than the other compounds, with the inhibition of 49.0% and 54.9% at a concentration of 50.0 µg/mL, respectively.
This Escherichia coli-produced bivalent HPV 16 and 18 vaccine was well tolerated and effective against HPV 16 and 18 associated high-grade genital lesions and persistent infection in interim analysis ...of this phase 3 trial. We now report data on long-term efficacy and safety after 66 months of follow-up.
This phase 3, double-blind, randomised, controlled trial was done in five study sites in China. Eligible participants were women aged 18–45 years, with intact cervix and 1–4 lifetime sexual partners. Women who were pregnant or breastfeeding, had chronic disease or immunodeficiency, or had HPV vaccination history were excluded. Women were stratified by age (18–26 and 27–45 years) and randomly (1:1) allocated by software (block randomisation with 12 codes to a block) to receive three doses of the E coli-produced HPV 16 and 18 vaccine or hepatitis E vaccine (control) and followed-up for 66 months. The primary outcomes were high-grade genital lesions and persistent infection (longer than 6 months) associated with HPV 16 or 18 in the per-protocol susceptible population. This trial was registered with ClinicalTrials.gov, NCT01735006.
Between Nov 22, 2012, and April 1, 2013, 8827 women were assessed for eligibility. 1455 women were excluded, and 7372 women were enrolled and randomly assigned to receive the HPV vaccine (n=3689) or control (n=3683). Vaccine efficacy was 100·0% (95% CI 67·2–100·0) against high-grade genital lesions (0 0% of 3310 participants in the vaccine group and 13 0·4% of 3302 participants in the control group) and 97·3% (89·9–99·7) against persistent infection (2 0·1% of 3262 participants in the vaccine group and 73 2·2% of 3271 participants in the control group) in the per-protocol population. Serious adverse events occurred at a similar rate between vaccine (267 7·2% of 3691 participants) and control groups (290 7·9% of 3681); none were considered related to vaccination.
The E coli-produced HPV 16 and 18 vaccine was well tolerated and highly efficacious against HPV 16 and 18 associated high-grade genital lesions and persistent infection and would supplement the global HPV vaccine availability and accessibility for cervical cancer prevention.
National Natural Science Foundation of China, National Key R&D Program of China, Fujian Provincial Project, Fundamental Funds for the Central Universities, Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, and Xiamen Innovax.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Electrochemical water splitting is convinced as one of the most promising solutions to combat the energy crisis. The exploitation of efficient hydrogen and oxygen evolution reaction (HER/OER) ...bifunctional electrocatalysts is undoubtedly a vital spark yet challenging for imperative green sustainable energy. Herein, through introducing a simple pH regulated redox reaction into a tractable hydrothermal procedure, a hierarchical Fe
3
O
4
@MnO
x
binary metal oxide core-shell nano-polyhedron was designed by evolving MnO
x
wrapped Fe
3
O
4
. The MnO
x
effectively prevents the agglomeration and surface oxidation of Fe
3
O
4
nano-particles and increases the electrochemically active sites. Benefiting from the generous active sites and synergistic effects of Fe
3
O
4
and MnO
x
, the Fe
3
O
4
@MnO
x
-NF nanocomposite implements efficient HER/OER bifunctional electrocatalytic performance and overall water splitting. As a result, hierarchical Fe
3
O
4
@MnO
x
only requires a low HER/OER overpotential of 242/188 mV to deliver 10 mA cm
−2
, a small Tafel slope of 116.4/77.6 mV dec
−1
, combining a long-term cyclability of 5 h. Impressively, by applying Fe
3
O
4
@MnO
x
as an independent cathode and anode, the overall water splitting cell supplies a competitive voltage of 1.64 V to achieve 10 mA cm
−2
and super long cyclability of 80 h. These results reveal that this material is a promising candidate for practical water electrolysis application.
A hierarchical Fe
3
O
4
@MnO
x
binary metal oxide core-shell nano-polyhedron executes excellent HER/OER bifunctional electrocatalytic activities due to abundant active sites and the synergistic effects of each component.
Diketopiperazine alkaloids have proven the most abundant heterocyclic alkaloids up to now, which usually process diverse scaffolds and rich biological activities. In our search for bioactive ...diketopiperazine alkaloids from marine-derived fungi, two novel diketopiperazine alkaloids, penipiperazine A (
1
) and its biogenetically related new metabolite (
2
), together with a known analogue neofipiperzine C (
3
), were obtained from the strain
Penicillium brasilianum
. Their planar structures and absolute configurations were elucidated by extensive spectroscopic analyses,
13
C NMR calculation, Marfey’s, ECD, and ORD methods. Compound
1
featured a unique 6/5/6/6/5 indole-pyrazino-pyrazino-pyrrolo system, and its plausible biogenetic pathway was also proposed. Additionally, compounds
1
–
3
have been tested for their inflammatory activities.
1
and
2
significantly inhibited the release of NO and the expression of related pro-inflammatory cytokines on LPS-stimulated RAW264.7 cells, suggesting they could be attracting candidate for further development as anti-inflammatory agent.
Key points
• A novel diketopiperazine alkaloid featuring a unique 6/5/6/6/5 indole-pyrazino-pyrazino-pyrrolo system was isolated from the marine fungus Penicillium brasilianum.
• The structure of
1
was elucidated by detailed analysis of 2D NMR data,
13
C NMR calculation, Marfey’s, ECD, and ORD methods.
• Compounds
1
and
2
significantly inhibited the release of NO and the expression of related pro-inflammatory cytokines on LPS-stimulated RAW264.7 cells.
Graphical Abstract
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Diabetic vascular smooth muscle cells (VSMCs) exhibit significantly increased rates of proliferation and migration, which was the most common pathological change in atherosclerosis. In addition, the ...study about the role for miRNAs in the regulation of VSMC proliferation is just beginning to emerge and additional miRNAs involved in VSMC proliferation modulation should be identified.
The expression of miR-138 and SIRT1 were examined in SMCs separated from db/db mice and in SMC lines C-12511 exposed to high glucose with qRT-PCR and western blot. The regulation of miR-138 on the expression of SMCs was detected with luciferase report assay. VSMCs proliferation and migration assays were performed to examine the effect of miR-138 inhibitor on VSMCs proliferation and migration.
We discovered that higher mRNA level of miR-138 and reduced expression of SIRT1 were observed in SMCs separated from db/db mice and in SMC lines C-12511. Moreover, luciferase report assay showed that the activity of SIRT1 3′-UTR was highly increased by miR-138 inhibitor and reduced by miR-138 mimic. In addition, we examined that the up-regulation of NF-κB induced by high glucose in SMCs was reversed by resveratrol and miR-138 inhibitor. MTT and migration assays showed that miR-138 inhibitor attenuated the proliferation and migration of smooth muscle cells.
In this study, we revealed that miR-138 might promote proliferation and migration of SMC in db/db mice through suppressing the expression of SIRT1.
•Higher mRNA level of miR-138 was observed in SMCs from db/db mice.•The mRNA and protein level of SIRT1 in SMCs from db/db mice were greatly reduced.•miR-138 could regulate the expression of SIRT1 in SMCs.•SIRT1 overexpression reversed the up-regulation of acetylized p65 and NF-κB induced by high glucose.•MiR-138 inhibitor reversed VSMCs proliferation and migration induced by high glucose.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Recently, 2D organic–inorganic hybrid lead halide perovskites have attracted intensive attention in solid‐state luminescence fields such as single‐component white‐light emitters, and rational ...optimization of the photoluminescence (PL) performance through accurate structural‐design strategies is still significant. Herein, by carefully choosing homologous aliphatic amines as templates, isotypical perovskites DMEDAPbCl4 (1, DMEDA=N,N‐dimethylethylenediamine) and DMPDAPbCl4 (2, DMPDA=N,N‐dimethyl‐1,3‐diaminopropane) having tunable and stable broadband bluish white emission properties were rationally designed. The subtle regulation of organic cations leads to a higher degree of distortion of the 2D PbCl42− layers and enhanced photoluminescence quantum efficiencies (<1 % for 1 and 4.9 % for 2). The broadband light emissions could be ascribed to self‐trapped excitons on the basis of structural characterization, time‐resolved PL, temperature‐dependent PL emission, and theoretical calculations. This work gives a new guidance to rationally optimize the PL properties of low‐dimensional halide perovskites and affords a platform to probe the structure–property relationship.
Shining white: With the aim of optimizing the broadband white‐light emission performance of low‐dimensional perovskites, isomorphic 2D perovskites DMEDAPbCl4 and DMPDAPbCl4 were structurally designed on the basis of homologous amine templates. The subtle regulation of organic cations leads to increased distortion of the 2D PbCl42− layers and enhancement of the photoluminescence quantum efficiency from <1 to 4.9 %. DMEDA: dimethylethylenediamine, DMPDA: N,N‐dimethyl‐1,3‐diaminopropane.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Mesoporous silica is widely used because of its unique and excellent properties, especially it can be used as a drug carrier and gene carrier in the biomedical field. After the mesoporous silica is ...put into clinical use, it is more likely to be exposed in human body. Therefore, the effect of mesoporous silica on human body cannot be ignored. The injury of vascular endothelial cells is a prerequisite for the occurrence of many cardiovascular diseases. As a drug and gene carrier, mesoporous silica increases its contact with vascular endothelial cells, so its toxic effect on cardiovascular system cannot be ignored. In this study, amino (NH2) and carboxyl (COOH) were modified on mesoporous silica SBA‐15 by post‐grafting. The results showed that it still maintained the one‐dimensional hexagonal mesoporous structure of SBA‐15 and had typical mesoporous structure. Then human umbilical vein endothelial cells (HUVECs) were infected with SBA‐15, NH2‐SBA‐15, and COOH‐SBA‐15. The results showed that the functionalized mesoporous silica SBA‐15 had cytotoxicity to HUVECs and damaged the cell membrane, but compared with the unmodified mesoporous silica SBA‐15 the cytotoxicity of functionalized mesoporous silica SBA‐15 was lower and the toxicity of carboxyl modified group was the lowest. By comparing the cell inhibition rate and the expression level of lactate dehydrogenate and reactive oxygen species induced by the three materials, oxidative damage and cell membrane damage may be two mechanisms of cytotoxicity. Mesoporous silica SBA‐15 has an effect on cardiovascular system by inducing the high expression of nitric oxide, intercellular adhesive molecule‐1 and vascular cell adhesive molecule‐1 in HUVECs. In summary, our results show that mesoporous silica is toxic to vascular endothelial cells.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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