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.
An easy method of preparing well-crystallized Sb2Se3 films and nanorods through magnetron sputtering was proposed, and their growth mechanism was examined. The microstructure, morphology, ...composition, and optical and electrical properties of the Sb2Se3 films depended strongly on the substrate temperature (Tsub). Sb2Se3 films prepared at > 250°C contained the orthorhombic phase without Sb2O3 phase owing to the high-purity vacuum environment. Well-crystallized Sb2Se3 films deposited at Tsub = 325°C showed compact grains with a bandgap of 1.23eV and a high absorption coefficient of 105cm−1 in the visible region. Photoelectrochemical measurements showed that Sb2Se3 films were p-type semiconductors with excellent photoresponse. A clear photovoltaic effect with a power conversion efficiency (PCE) of 3.35% was measured for the first time by using the sputtering Sb2Se3 films as absorbers in a photovoltaic solar cell. At Tsub = 375°C, highly uniform films with monodispersed Sb2Se3 nanorods were obtained. The preferential orientation of the Sb2Se3 crystals by self-organization was promoted by increasing Tsub. By using the Sb2Se3 nanorods as absorbers in a solar cell, good photoresponse and a PCE of 2.15% were achieved.
•Thermally induced mechanism of Sb2Se3 film and nano-rod prepared by sputtering.•Tsub is the key for Sb2Se3 films and an efficient self-organization for nano-rods.•High crystalline Sb2Se3 film prepared at 325°C, 3.35% PCE in solar cell achieved.
Cirrhosis develops from liver fibrosis and is the severe pathological stage of all chronic liver injury. Cirrhosis caused by hepatitis B virus and hepatitis C virus infection is especially common. ...Liver fibrosis and cirrhosis involve excess production of extracellular matrix,which is closely related to liver sinusoidal endothelial cells(LSECs). Damaged LSECs can synthesize transforming growth factor-beta and platelet-derived growth factor,which activate hepatic stellate cells and facilitate the synthesis of extracellular matrix. Herein,we highlight the angiogenic cytokines of LSECs related to liver fibrosis and cirrhosis at different stages and focus on the formation and development of liver fibrosis and cirrhosis. Inhibition of LSEC angiogenesis and antiangiogenic therapy are described in detail. Targeting LSECs has high therapeutic potential for liver diseases. Further understanding of the mechanism of action will provide stronger evidence for the development of anti-LSEC drugs and new directions for diagnosis and treatment of liver diseases.
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.
COVID-19 pandemic has already produced great impacts on global health security and social-economy. Elderly, particularly those with underlying diseases, are suffering from higher fatality rate. ...Neurodegenerative diseases are a group of incurable neurological disorders of loss of neuron and/or myelin sheath, which affect hundreds of millions of elderly populations and usually need long-term care. Older population is one of the most vulnerable to COVID-19 pandemic. In this report, we reviewed the current status of COVID-19 on the patients with several neurodegenerative diseases, particularly Alzheimer's disease, Parkinson's disease, prion disease, and amyotrophic lateral sclerosis. Meanwhile, the potential mechanisms of SARS-CoV-2 infection in the pathogenesis of neurodegenerative diseases were also summarized.
The first organocatalytic asymmetric synthesis of an advanced intermediate of (+)‐sarain A was achieved. This approach featured the employment of an organocatalytic asymmetric Michael addition ...reaction and a nitrogen‐to‐carbon chirality transfer to forge three chiral centers, as well as a catalytic hydrosilylation for the chemoselective reduction of a key lactam intermediate. The tricyclic intermediate contained all the required functionalities for elaborating into (+)‐sarain A.
Get asymmetric: The first organocatalytic asymmetric synthesis of an advanced intermediate of (+)‐sarain A features an organocatalytic asymmetric Michael addition reaction and a nitrogen‐to‐carbon chirality transfer to forge three chiral centers, as well as a catalytic hydrosilylation for the chemoselective reduction of a key lactam intermediate.
•Co-overexpression of HMG1 and DGA1 improved the squalene production in Y. lipolytica.•The highest titer of squalene at 731.18 mg/L was produced in Y. lipolytica.•This study will provide the ...foundation for cost-efficiently producing squalene.
The aim of this present research is to enhance the squalene production in Yarrowia lipolytica using pathway engineering and bioprocess engineering. Firstly, to improve the production of squalene, the endogenous HMG-CoA reductase (HMG1) was overexpressed in Y. lipolytica to yield 208.88 mg/L squalene. Secondly, the HMG1 and diacylglycerol acyltranferase (DGA1) were co-overexpressed, the derived recombinant Y. lipolytica SQ-1 strain produced 439.14 mg/L of squalene. Thirdly, by optimizing the fermentation medium, the improved titer of squalene with 514.34 mg/L was obtained by the engineered strain SQ-1 grown on YPD-80 medium. Finally, by optimizing the addition concentrations of acetate, citrate and terbinafine, the 731.18 mg/L squalene was produced in the engineered strain SQ-1 with the addition of 0.5 mg/L terbinafine. This work describes the highest reported squalene titer in Y. lipolytica to date. This study will provide the foundation for further engineering Y. lipolytica capable of cost-efficiently producing squalene.
A new RNA-selective fluorescent dye integrated with a thiazole orange and a p-(methylthio)styryl moiety shows better nucleolus RNA staining and imaging performance in live cells than the commercial ...stains. It also exhibits excellent photostability, cell tolerance, and counterstain compatibility with 4',6-diamidino-2-phenylindole for specific RNA-DNA colocalization in bioassays.
The rapid development of HSR has brought great convenience to people, especially those on long-distance journeys. Existing communication technologies are quite limited in satisfying the challenging ...demands of HSR networks, providing poor quality of experience for HSR passengers (e.g., frequent link failures and long network delays). 5G mobile communications are expected to overcome these challenging issues in current HSR networks. In this article, we focus on the great innovations of a novel smart network architecture for 5G communications, and propose a specific SCN-R to promote efficient and reliable communications in HSR scenarios. Experiment results have verified that SCN-R provides an efficient solution to improve the usage of network resources and the quality of service with respect to the existing state-of-the-art solutions.
The precise circuit of the substantia nigra pars reticulata (SNr) involved in temporal lobe epilepsy (TLE) is still unclear. Here we found that optogenetic or chemogenetic activation of SNr ...parvalbumin
(PV) GABAergic neurons amplifies seizure activities in kindling- and kainic acid-induced TLE models, whereas selective inhibition of these neurons alleviates seizure activities. The severity of seizures is bidirectionally regulated by optogenetic manipulation of SNr PV fibers projecting to the parafascicular nucleus (PF). Electrophysiology combined with rabies virus-assisted circuit mapping shows that SNr PV neurons directly project to and functionally inhibit posterior PF GABAergic neurons. Activity of these neurons also regulates seizure activity. Collectively, our results reveal that a long-range SNr-PF disinhibitory circuit participates in regulating seizure in TLE and inactivation of this circuit can alleviate severity of epileptic seizures. These findings provide a better understanding of pathological changes from a circuit perspective and suggest a possibility to precisely control epilepsy.
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