This is the first randomised controlled trial for assessment of the immunogenicity and safety of a candidate non-replicating adenovirus type-5 (Ad5)-vectored COVID-19 vaccine, aiming to determine an ...appropriate dose of the candidate vaccine for an efficacy study.
This randomised, double-blind, placebo-controlled, phase 2 trial of the Ad5-vectored COVID-19 vaccine was done in a single centre in Wuhan, China. Healthy adults aged 18 years or older, who were HIV-negative and previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-free, were eligible to participate and were randomly assigned to receive the vaccine at a dose of 1 × 1011 viral particles per mL or 5 × 1010 viral particles per mL, or placebo. Investigators allocated participants at a ratio of 2:1:1 to receive a single injection intramuscularly in the arm. The randomisation list (block size 4) was generated by an independent statistician. Participants, investigators, and staff undertaking laboratory analyses were masked to group allocation. The primary endpoints for immunogenicity were the geometric mean titres (GMTs) of specific ELISA antibody responses to the receptor binding domain (RBD) and neutralising antibody responses at day 28. The primary endpoint for safety evaluation was the incidence of adverse reactions within 14 days. All recruited participants who received at least one dose were included in the primary and safety analyses. This study is registered with ClinicalTrials.gov, NCT04341389.
603 volunteers were recruited and screened for eligibility between April 11 and 16, 2020. 508 eligible participants (50% male; mean age 39·7 years, SD 12·5) consented to participate in the trial and were randomly assigned to receive the vaccine (1 × 1011 viral particles n=253; 5 × 1010 viral particles n=129) or placebo (n=126). In the 1 × 1011 and 5 × 1010 viral particles dose groups, the RBD-specific ELISA antibodies peaked at 656·5 (95% CI 575·2–749·2) and 571·0 (467·6–697·3), with seroconversion rates at 96% (95% CI 93–98) and 97% (92–99), respectively, at day 28. Both doses of the vaccine induced significant neutralising antibody responses to live SARS-CoV-2, with GMTs of 19·5 (95% CI 16·8–22·7) and 18·3 (14·4–23·3) in participants receiving 1 × 1011 and 5 × 1010 viral particles, respectively. Specific interferon γ enzyme-linked immunospot assay responses post vaccination were observed in 227 (90%, 95% CI 85–93) of 253 and 113 (88%, 81–92) of 129 participants in the 1 × 1011 and 5 × 1010 viral particles dose groups, respectively. Solicited adverse reactions were reported by 183 (72%) of 253 and 96 (74%) of 129 participants in the 1 × 1011 and 5 × 1010 viral particles dose groups, respectively. Severe adverse reactions were reported by 24 (9%) participants in the 1 × 1011 viral particles dose group and one (1%) participant in the 5 × 1010 viral particles dose group. No serious adverse reactions were documented.
The Ad5-vectored COVID-19 vaccine at 5 × 1010 viral particles is safe, and induced significant immune responses in the majority of recipients after a single immunisation.
National Key R&D Programme of China, National Science and Technology Major Project, and CanSino Biologics.
We explored whether medical health workers had more psychosocial problems than nonmedical health workers during the COVID-19 outbreak.
An online survey was run from February 19 to March 6, 2020; a ...total of 2,182 Chinese subjects participated. Mental health variables were assessed via the Insomnia Severity Index (ISI), the Symptom Check List-revised (SCL-90-R), and the Patient Health Questionnaire-4 (PHQ-4), which included a 2-item anxiety scale and a 2-item depression scale (PHQ-2).
Compared with nonmedical health workers (n = 1,255), medical health workers (n = 927) had a higher prevalence of insomnia (38.4 vs. 30.5%, p < 0.01), anxiety (13.0 vs. 8.5%, p < 0.01), depression (12.2 vs. 9.5%; p< 0.04), somatization (1.6 vs. 0.4%; p < 0.01), and obsessive-compulsive symptoms (5.3 vs. 2.2%; p < 0.01). They also had higher total scores of ISI, GAD-2, PHQ-2, and SCL-90-R obsessive-compulsive symptoms (p ≤ 0.01). Among medical health workers, having organic disease was an independent factor for insomnia, anxiety, depression, somatization, and obsessive-compulsive symptoms (p < 0.05 or 0.01). Living in rural areas, being female, and being at risk of contact with COVID-19 patients were the most common risk factors for insomnia, anxiety, obsessive-compulsive symptoms, and depression (p < 0.01 or 0.05). Among nonmedical health workers, having organic disease was a risk factor for insomnia, depression, and obsessive-compulsive symptoms (p < 0.01 or 0.05).
During the COVID-19 outbreak, medical health workers had psychosocial problems and risk factors for developing them. They were in need of attention and recovery programs.
Gut Microbiota-brain Axis Wang, Hong-Xing; Wang, Yu-Ping
Chinese medical journal,
10/2016, Letnik:
129, Številka:
19
Journal Article
Recenzirano
Odprti dostop
Objective: To systematically review the updated information about the gut microbiota-brain axis.
Data Sources: All articles about gut microbiota-brain axis published up to July 18, 2016, were ...identified through a literature search on PubMed, ScienceDirect, and Web of Science, with the keywords of "gut microbiota", "gut-brain axis", and "neuroscience".
Study Selection: All relevant articles on gut microbiota and gut-brain axis were included and carefully reviewed, with no limitation of study design.
Results: It is well-recognized that gut microbiota affects the brain's physiological, behavioral, and cognitive functions although its precise mechanism has not yet been fully understood. Gut microbiota-brain axis may include gut microbiota and their metabolic products, enteric nervous system, sympathetic and parasympathetic branches within the autonomic nervous system, neural-immune system, neuroendocrine system, and central nervous system. Moreover, there may be five communication routes between gut microbiota and brain, including the gut-brain's neural network, neuroendocrine-hypothalamic-pituitary-adrenal axis, gut immune system, some neurotransmitters and neural regulators synthesized by gut bacteria, and barrier paths including intestinal mucosal barrier and blood-brain barrier. The microbiome is used to define the composition and functional characteristics of gut microbiota, and metagenomics is an appropriate technique to characterize gut microbiota.
Conclusions: Gut microbiota-brain axis refers to a bidirectional information network between the gut microbiota and the brain, which may provide a new way to protect the brain in the near future.
Synergistic use of electrochemistry and organometallic catalysis has emerged as a powerful tool for site-selective C–H functionalization, yet this type of transformation has thus far mainly been ...limited to arene C–H functionalization. Herein, we report the development of electrochemical vinylic C–H functionalization of acrylic acids with alkynes. In this reaction an iridium catalyst enables C–H/O–H functionalization for alkyne annulation, affording α-pyrones with good to excellent yields in an undivided cell. Preliminary mechanistic studies show that anodic oxidation is crucial for releasing the product and regeneration of an Ir(III) intermediate from a diene-Ir(I) complex, which is a coordinatively saturated, 18-electron complex. Importantly, common chemical oxidants such as Ag(I) or Cu(II) did not give significant amounts of the desired product in the absence of electrical current under otherwise identical conditions.
A scalable enantioselective nickel-catalyzed electrochemical reductive homocoupling of aryl bromides has been developed, affording enantioenriched axially chiral biaryls in good yield under mild ...conditions using electricity as a reductant in an undivided cell. Common metal reductants such as Mn or Zn powder resulted in significantly lower yields in the absence of electric current under otherwise identical conditions, underscoring the enhanced reactivity provided by the combination of transition metal catalysis and electrochemistry.
Heterogeneous noble‐metal‐based catalysis plays an essential role in the production of fine chemicals. Rh‐based catalysts are one of the most active candidates for indole synthesis. However, it is ...still highly desired to develop heterogeneous Rh‐based catalysts with high activity and selectivity. In this work, a general, facile wet‐chemical method is reported to synthesize ultrathin amorphous/crystalline heterophase Rh and Rh‐based bimetallic alloy nanosheets (NSs), including RhCu, RhZn, and RhRu. Impressively, the amorphous/crystalline heterophase Rh NSs exhibit enhanced catalytic activity toward the direct synthesis of indole compared to the crystalline counterpart. Importantly, the obtained amorphous/crystalline heterophase RhCu alloy NSs can further enhance the selectivity to indole of >99.9% and the conversion is 100%. This work demonstrates the importance of phase engineering and metal alloying in the rational design and synthesis of tandem heterogeneous catalysts toward fine chemical synthesis.
Ultrathin Rh and RhM (M = Cu, Zn, Ru) alloy nanosheets with amorphous/crystalline heterophases are successfully synthesized. In tandem catalysis to directly synthesize indole, the amorphous/crystalline heterophase Rh nanosheets (NSs) outperform their crystalline counterpart, demonstrating much higher catalytic activity. Impressively, the amorphous/crystalline heterophase RhCu NSs show dramatically enhanced indole selectivity of over 99.9% and excellent activity.
Phloem-feeding insects feed on plant phloem using their stylets. While ingesting phloem sap, these insects secrete saliva to circumvent plant defenses. Previous studies have shown that, to facilitate ...their feeding, many phloem-feeding insects can elicit the salicylic acid- (SA-) signaling pathway and thus suppress effective jasmonic acid defenses. However, the molecular basis for the regulation of the plant’s defense by phloem-feeding insects remains largely unknown. Here, we show that Bt56, a whitefly-secreted low molecular weight salivary protein, is highly expressed in the whitefly primary salivary gland and is delivered into host plants during feeding. Overexpression of the Bt56 gene in planta promotes susceptibility of tobacco to the whitefly and elicits the SA-signaling pathway. In contrast, silencing the whitefly Bt56 gene significantly decreases whitefly performance on host plants and interrupts whitefly phloem feeding with whiteflies losing the ability to activate the SA pathway. Protein-protein interaction assays show that the Bt56 protein directly interacts with a tobacco KNOTTED 1-like homeobox transcription factor that decreases whitefly performance and suppresses whitefly-induced SA accumulation. The Bt56 orthologous genes are highly conserved but differentially expressed in different species of whiteflies. In conclusion, Bt56 is a key salivary effector that promotes whitefly performance by eliciting salicylic acid-signaling pathway.
An enhancement-mode hydrogen-terminated diamond field-effect transistor (FET) is realized by using a low work function gate material, namely, lanthanum hexaboride (LaB 6 ). The reason for the ...enhancement mode should be that the electrons in the LaB 6 layer flow into the two-dimensional hole gas (2DHG) channel and compensate the holes, such that the channel is shut down. The threshold voltages (<inline-formula> <tex-math notation="LaTeX">{\mathrm {V}}_{\text {TH}} </tex-math></inline-formula>) range from − 0.29 V to − 0.72 V with different gate lengths. The device with 2 <inline-formula> <tex-math notation="LaTeX">\mu \text{m} </tex-math></inline-formula> gate length shows a − 57.9 mA/mm maximum drain current density (<inline-formula> <tex-math notation="LaTeX">{\mathrm {I}}_{\text {DSmax}} </tex-math></inline-formula>) at <inline-formula> <tex-math notation="LaTeX">{\mathrm {V}}_{\text {GS}} =- </tex-math></inline-formula> 5 V. The on/off ratio is around 9 orders of magnitude, with a subthreshold swing of 130 mV. Effective mobility (<inline-formula> <tex-math notation="LaTeX">\mu _{\text {eff}} </tex-math></inline-formula>) as high as 195.4 cm 2 /<inline-formula> <tex-math notation="LaTeX">\text{V}\cdot \text{s} </tex-math></inline-formula> is obtained from the device. This technique reveals undamaged 2 DHG characteristics, uncontaminated interface between LaB 6 and aluminum gate metal, and a simple fabrication process, which will promote the development of enhancement diamond FETs.
Materials exhibiting excitation wavelength‐dependent photoluminescence (Ex‐De PL) in the visible region have potential applications in bioimaging, optoelectronics and anti‐counterfeiting. Two ...multifunctional, chiral Au(NHC)2Au(CN)2 (NHC=(4R,5R)/(4S,5S)‐1,3‐dimethyl‐4,5‐diphenyl‐4,5‐dihydro‐imidazolin‐2‐ylidene) complex double salts display Ex‐De circularly polarized luminescence (CPL) in doped polymer films and in ground powder. Emission maxima can be dynamically tuned from 440 to 530 nm by changing the excitation wavelength. The continuously tunable photoluminescence is proposed to originate from multiple emissive excited states as a result of the existence of varied AuI⋅⋅⋅AuI distances in ground state. The steric properties of the NHC ligand are crucial to the tuning of AuI⋅⋅⋅AuI distances. An anti‐counterfeiting application using these two salts is demonstrated.
Ex‐De CPL: By modulating the strength of AuI⋅⋅⋅AuI and Coulombic interactions by adjusting steric hindrance of the ligand, together with the materials processing, the two chiral enantiomers of Au(NHC)2Au(CN)2 double salts in PMMA film or as ground powder exhibit mirror‐image excitation wavelength‐dependent photoluminescence (Ex‐De CPL).
We investigate essential relationships between generalization capabilities and fuzziness of fuzzy classifiers (viz., the classifiers whose outputs are vectors of membership grades of a pattern to the ...individual classes). The study makes a claim and offers sound evidence behind the observation that higher fuzziness of a fuzzy classifier may imply better generalization aspects of the classifier, especially for classification data exhibiting complex boundaries. This observation is not intuitive with a commonly accepted position in "traditional" pattern recognition. The relationship that obeys the conditional maximum entropy principle is experimentally confirmed. Furthermore, the relationship can be explained by the fact that samples located close to classification boundaries are more difficult to be correctly classified than the samples positioned far from the boundaries. This relationship is expected to provide some guidelines as to the improvement of generalization aspects of fuzzy classifiers.
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