Summary Background Seroprevalence data suggest that a third of the world's population has been infected with the hepatitis E virus. Our aim was to assess efficacy and safety of a recombinant ...hepatitis E vaccine, HEV 239 (Hecolin; Xiamen Innovax Biotech, Xiamen, China) in a randomised, double-blind, placebo-controlled, phase 3 trial. Methods Healthy adults aged 16–65 years in, Jiangsu Province, China were randomly assigned in a 1:1 ratio to receive three doses of HEV 239 (30 μg of purified recombinant hepatitis E antigen adsorbed to 0·8 mg aluminium hydroxide suspended in 0·5 mL buffered saline) or placebo (hepatitis B vaccine) given intramuscularly at 0, 1, and 6 months. Randomisation was done by computer-generated permuted blocks and stratified by age and sex. Participants were followed up for 19 months. The primary endpoint was prevention of hepatitis E during 12 months from the 31st day after the third dose. Analysis was based on participants who received all three doses per protocol. Study participants, care givers, and investigators were all masked to group and vaccine assignments. This trial is registered with ClinicalTrials.gov , number NCT01014845. Findings 11 165 of the trial participants were tested for hepatitis E virus IgG, of which 5285 (47%) were seropositive for hepatitis E virus. Participants were randomly assigned to vaccine (n=56 302) or placebo (n=56 302). 48 693 (86%) participants in the vaccine group and 48 663 participants (86%) in the placebo group received three vaccine doses and were included in the primary efficacy analysis. During the 12 months after 30 days from receipt of the third dose 15 per-protocol participants in the placebo group developed hepatitis E compared with none in the vaccine group. Vaccine efficacy after three doses was 100·0% (95% CI 72·1–100·0). Adverse effects attributable to the vaccine were few and mild. No vaccination-related serious adverse event was noted. Interpretation HEV 239 is well tolerated and effective in the prevention of hepatitis E in the general population in China, including both men and women age 16–65 years. Funding Chinese National High-tech R&D Programme (863 programme), Chinese National Key Technologies R&D Programme, Chinese National Science Fund for Distinguished Young Scholars, Fujian Provincial Department of Sciences and Technology, Xiamen Science and Technology Bureau, and Fujian Provincial Science Fund for Distinguished Young Scholars.
The efficacy of osimertinib was compromised by the development of resistance mechanisms, such as EGFR C797S. In vitro study proved that cells harboring EGFR C797S in trans with T790M are sensitive to ...a combination of first- and third-generation EGFR tyrosine kinase inhibitors. However, this has not been reported clinically.
We performed capture-based sequencing on longitudinal plasma samples obtained at various treatment milestones from a patient with advanced lung adenocarcinoma who was undergoing targeted therapy.
At the development of resistance to osimertinib, the patient’s plasma sample revealed EGFR C797S located in trans with T790M. He achieved partial response accompanied by undetectable C797S after commencement of a combinatorial treatment consisting of erlotinib and osimertinib. After 3 months of progression-free survival, he experienced progressive disease with emergence of EGFR C797S located in cis to T790M.
We report the first clinical evidence of efficacy generated by combination therapy consisting of first- and third-generation EGFR tyrosine kinase inhibitors targeting concomitant EGFR T790M and C797S in trans. We also reveal that the clonal progression of C797S from in trans to in cis at disease progression may serve as a potential resistance mechanism.
This article is concerned with the distributed filtering issue for linear discrete-time systems under bounded noises and constrained bit rate over wireless sensor networks. The communication between ...different sensor nodes is implemented via a wireless digital communication network with limited bandwidth. A bit rate constraint, which is subject to the so-called bandwidth allocation strategy, is placed to quantify the effect of the network bandwidth on the distributed filtering performance. An improved coding-decoding procedure is proposed to enable each node to decode messages from its neighbor nodes. Based on this procedure, a decoded-innovation-based distributed filtering scheme is put forward and a sufficient condition is established to ensure that the filtering error dynamics is ultimately bounded. Subsequently, a relationship between the bit rate and certain specific filtering performance is discovered. The desired parameters of the distributed filter are determined via solving two optimization problems whose objectives are actually the filtering performance indices including the smallest ultimate bound and the fastest decay rate. Furthermore, the codesign issue of the bit rate allocation protocol and the filter gain is converted into the mixed integer nonlinear programming problem, which is solved by means of the particle swarm optimization algorithm and the linear matrix inequality technique. Finally, numerical simulations on three scenarios are provided to verify the validity of the proposed distributed filtering approach.
Parkinson’s disease (PD) is one of the most common neurodegenerative diseases. Although its pathogenesis remains unclear, a number of studies indicate that microglia‐mediated neuroinflammation makes ...a great contribution to the pathogenesis of PD. Melatonin receptor 1 (MT1) is widely expressed in glia cells and neurons in substantia nigra (SN). Neuronal MT1 is a neuroprotective factor, but it remains largely unknown whether dysfunction of microglial MT1 is involved in the PD pathogenesis. Here, we found that MT1 was reduced in microglia of SN in 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐induced PD mouse model. Microglial MT1 activation dramatically inhibited lipopolysaccharide (LPS)‐induced neuroinflammation, whereas loss of microglial MT1 aggravated it. Metabolic reprogramming of microglia was found to contribute to the anti‐inflammatory effects of MT1 activation. LPS‐induced excessive aerobic glycolysis and impaired oxidative phosphorylation (OXPHOS) could be reversed by microglial MT1 activation. MT1 positively regulated pyruvate dehydrogenase alpha 1 (PDHA1) expression to enhance OXPHOS and suppress aerobic glycolysis. Furthermore, in LPS‐treated microglia, MT1 activation decreased the toxicity of conditioned media to the dopaminergic (DA) cell line MES23.5. Most importantly, the anti‐inflammatory effects of MT1 activation were observed in LPS‐stimulated mouse model. In general, our study demonstrates that MT1 activation inhibits LPS‐induced microglial activation through regulating its metabolic reprogramming, which provides a mechanistic insight for microglial MT1 in anti‐inflammation.
A schematic diagram shows the involvement of metabolic reprogramming in MT1 activation‐mediated inhibition of LPS‐induced microglial activation. Once microglia suffered LPS insults, microglia would transfer into over‐activated state, accompanied by converting their metabolic status from OXPHOS to aerobic glycolysis. However, microglial MT1 activation could promote PDHA1 expression, leading to reverse LPS‐mediated microglial metabolic reprogramming, thereby, suppressing microglial activation.
Bed material transport at river bifurcations is crucial for channel stability and downstream geomorphic dynamics. However, measurements of bed material transport at bifurcations of large alluvial ...rivers are difficult to make, and standard estimates based on the assumption of proportional partitioning of flow and bedload transport at bifurcations may be erroneous. In this study, we employed a combined approach based on observed topographic change (erosion/deposition) and bed material transport predicted from a one‐dimensional model to investigate bed material fluxes near the engineering‐controlled Mississippi‐Atchafalaya River diversion, which is of great importance to sediment distribution and delivery to Louisiana's coast. Yang's (1973) sediment transport equation was utilized to estimate daily bed material loads upstream, downstream, and through the diversion during 2004–2013. Bathymetric changes in these channels were assessed with single beam data collected in 2004 and 2013. Results show that over the study period, 24% of the Mississippi River flow was diverted into the Atchafalaya River, while the rest remained in the mainstem Mississippi. Upstream of the diversion, the bed material yield was predicted to be 201 million metric tons (MT), of which approximately 35 MT (i.e., 17%) passed through the bifurcation channel to the Atchafalaya River. The findings from this study reveal that in the mainstem Mississippi, the percentage of bed material diversion (83%) is larger than the percentage of flow diversion (76%); Conversely, the diversion channel receives a disproportionate amount of flow (24%) relative to bed material supply (17%). Consequently, severe bed scouring occurred in the controlled Outflow Channel to the Atchafalaya River, while riverbed aggradation progressed in the mainstem Mississippi downstream of the diversion structures, implying reduced flow capacity and potential risk of a high backwater during megafloods. The study demonstrates that Yang's sediment transport equation provides plausible results of bed material fluxes for a highly complicated large river diversion, and that integration of the sediment transport equation with observed morphological changes in riverbed is a valuable approach to investigate sediment dynamics at controlled river bifurcations.
A combined approach of channel morphological assessment and bedload calculation with a 1‐D sediment transport equation was employed to investigate bed material fluxes near a large engineering‐controlled river diversion.
Underwater visible light communication (UVLC) is of great interest to the military, industry, and the scientific community. In this paper, a long-distance UVLC system is designed, where the half ...power angle of light-emitting diode (LED) is narrowed to enhance the optical intensity at the transmitter, and a single photon avalanche diode (SPAD) is employed at the receiver to improve the detection sensitivity. A two-term exponential channel model of a long distance UVLC system with a SPAD receiver is established, and the channel parameters are obtained by Monte Carlo numerical simulation. Furthermore, the SPAD detection algorithm and the optimal detection threshold of the UVLC system are proposed. Simulation results show that the communication distance could be extended to 500 m in pure seawater.
Nanoparticles have been widely used in the improvement of the mechanical and thermal properties of the epoxy matrix. In this study, the room temperature curing agent composed of acrylic acid and ...2,4,6‐trimethyl‐m‐phenylenediamine was mixed with different concentrations of CeO2 nanoparticles into the epoxy resin (E51) to obtain a nanocomposite that can be rapidly molded and cured. Fourier transform infrared spectroscopy and differential scanning calorimetry were used to study the curing behavior of nanocomposites and E51 with the synthesized hardener. Through tensile, flexural, and impact tests, the influence of the nanoparticles content on the mechanical and thermal properties of the prepared composites was discussed. The results showed that the curing process was completed in 4 h. An increase of 78.4% in tensile strength, 81.7% in flexural strength, and 122.0% in elongation were obtained for the cured nanocomposite having 5 wt% CeO2 loading compared to the neat resin. Thermogravimetric analysis result showed that the thermal stability increased with increasing of CeO2 nanofillers content. Finally, the scanning electron microscope revealed the fracture surface morphology of the composites.
CeO2‐enhanced epoxy matrix nanocomposites were prepared without external heating by using a novel hardener derived from acrylic acid and 2,4,6‐trimethyl‐m‐phenylenediamine. The obtained nanocomposites display the improved mechanical and thermal properties.
Background
Sleep disorders are associated with temporomandibular disorders (TMDs). Limited studies have focused on excessive daytime sleepiness (EDS) and its impact on jaw functions in TMD patients.
...Objective
The aim of the present investigation was to identify the impact of EDS on pain and jaw function in TMD patients.
Methods
A total of 338 TMD patients (50 males and 288 females) was included. The Epworth Sleepiness Scale (ESS) was used to classify patients into EDS group (score ≥ 10) and non‐EDS group (score < 10). The Jaw Functional Limitation Scale 8‐item (JFLS‐8) was used to assess the severity of jaw dysfunction. Pain intensity was evaluated using the Visual Analogue Scale (VAS). Anxiety and depression were evaluated using the Generalised Anxiety Disorder 7‐item (GAD‐7) and the Patient Health Questionnaire 9‐item (PHQ‐9). All included patients were diagnosed with pain‐related TMD (PT), intra‐articular TMD (IT) or combined TMD (CT).
Results
Compared with non‐EDS patients, EDS patients exhibited more severe jaw dysfunction, greater pain intensity and higher PHQ‐9 scores (p < .05). Multivariate analyses showed that EDS (B = 3.69), female gender (B = 3.69), and elevated GAD‐7 score (B = 0.73) were significantly associated with an increased score on the JFLS‐8 (p < .05). Moreover, bivariate logistic regression analysis indicated a significant relationship between EDS and PT (OR = 2.70, p = .007).
Conclusion
The presence of EDS was more closely related to PT, but the causal relationship between them needs to be further confirmed. More concern and intervention to alleviate poor sleep quality might be highlighted during the treatment of TMD, especially PT subtype.
The presence of excessive daytime sleepiness was significantly associated with increased odds of pain‐related temporomandibular disorders and a higher score on the jaw functional limitation scale.
Novel quinoxaline‐based trismaleimide (2,3‐di3‐maleimidophenyl‐6‐ maleimidoquinoxaline, namely TQMI) and its polymer alloys with 3‐phenyl‐3,4‐dihydro‐2H‐1,3‐benzoxazine (P‐a) were successfully ...prepared and characterized. Differential scanning calorimetry investigation of TQMI exhibited distinct double exothermic peaks, which implied that the curing behavior of different type of maleimide group was discrepant. The curing temperature of P‐a/TQMI prepolymers was lower than that of both neat TQMI and P‐a monomer. The temperatures at 5% (T5) and 10% (T10) weight loss and the char yield (Yc) of cured TQMI at 800°C reached 513°C, 524°C, and 63.5%, respectively, which were much higher than the record of traditional 4,4′‐bismaleimideodiphenylmethane (BMDPM) resin as well as most of other reported bismaleimide resins. Moreover, the addition of TQMI enhanced thermal stability, glass transition temperature (Tg), and limiting oxygen index of benzoxazine resin dramatically. Attractively, the Tg value of P‐a/TQMI copolymer at 30 wt% TQMI loadings was approximately 20°C higher than that of P‐a/BMDPM copolymer owing to the bulky quinoxaline group.
Orchidaceae, renowned for its spectacular flowers and other reproductive and ecological adaptations, is one of the most diverse plant families. Here we present the genome sequence of the tropical ...epiphytic orchid Phalaenopsis equestris, a frequently used parent species for orchid breeding. P. equestris is the first plant with crassulacean acid metabolism (CAM) for which the genome has been sequenced. Our assembled genome contains 29,431 predicted protein-coding genes. We find that contigs likely to be underassembled, owing to heterozygosity, are enriched for genes that might be involved in self-incompatibility pathways. We find evidence for an orchid-specific paleopolyploidy event that preceded the radiation of most orchid clades, and our results suggest that gene duplication might have contributed to the evolution of CAM photosynthesis in P. equestris. Finally, we find expanded and diversified families of MADS-box C/D-class, B-class AP3 and AGL6-class genes, which might contribute to the highly specialized morphology of orchid flowers.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SBMB, UILJ, UKNU, UL, UM, UPUK
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