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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) protein subunit vaccine is one of the mainstream technology platforms for the development of COVID-19 vaccines, and most R&D units use the receptor-binding domain (RBD) or spike (S) protein as the main target antigen. The complexity of vaccine design, sequence, and expression systems makes it urgent to establish common antigen assays to facilitate vaccine development. In this study, we report the development of a double-antibody sandwich enzyme-linked immunosorbent assay (ELISA) to determine the antigen content of SARS-CoV-2 protein subunit vaccines based on the United States Pharmacopeia and ICH (international conference on harmonization) Q14 and Q2 (R2) requirements. A monoclonal antibody (mAb), 20D8, was identified as the detection antibody based on its high RBD binding activity (EC50 = 8.4 ng/mL), broad-spectrum anti-variant neutralizing activity (EC50: 2.7–9.8 ng/mL for pseudovirus and EC50: 9.6–127 ng/mL for authentic virus), good in vivo protection, and a recognized linear RBD epitope (369–379 aa). A porcine anti-RBD polyclonal antibody was selected as the coating antibody. Assay performance met the requirements of the analytical target profile with an accuracy and precision of ≥90% and adequate specificity. Within the specification range of 70–143%, the method capability index was >0.96; the misjudgment probability was

Summary: Background: China's three inactivated enterovirus A71 (EV-A71) vaccines are the first and currently world's only EV-A71 vaccines approved by a national regulatory authority and used to prevent EV-A71 associated diseases. The three vaccines vary by vaccine strain, manufacturing cell substrate, and antigen dose, but no head-to-head comparisons of these vaccines have been done. We compared immunogenicity of the vaccines in children 6-35 months old. Methods: We recruited healthy children aged 6-35 months who lived in a study site county into a multicentre, open-label, non-inferiority, three-group, randomised controlled trial that was conducted in five counties in China. Enrolled children were randomly assigned (1:1:1) to receive two doses of one of the three EV-A71 vaccines. The primary outcome was the proportion of children with EV-A71 neutralizing antibody seroconversion 4 weeks after the second dose; a secondary outcome was adverse events in the 4 weeks after each dose. Analyses of immunogenicity included all children who completed the study (per-protocol analysis). Safety analysis included all children completed safety follow-up after at least one. We used a 10% margin to establish non-inferiority. This trial was registered on a World Health Organization platform: Chinese Clinical Trial Registry (ChiCTR1900026663). Findings: 1631 children were assessed for eligibility between Nov 4 and Nov 20, 2019. Of 1500 (92%) enrolled children, 500 were assigned to vaccine group A, B, or C; 483 in group A,484 in group B, and 487 in group C completed the study. Before dose one, the seropositive rates in groups A, B, and C were 9.7%, 7.2%, and 7.0%. Four weeks after the second dose, seroconversion rates of groups A, B, and C were 98.8%, 99.4% and 99.8% - mutually non-inferior in all two-group comparisons. There were no serious adverse events in any group and no evidence of a difference among the three groups in the incidence of local adverse event or systemic adverse event. Fever was the most common adverse event. All children with reported adverse events recovered. Interpretation: Non-inferior and high seroconversion rates and equivalent safety of three EV-A71 vaccines supports use any of these vaccines to prevent EV-A71-associated diseases. These results may be useful for regulators, vaccine policy makers, and immunization programmes in China and in countries where EV-A71 is endemic.

A chemical synapse is either an action potential (AP) synapse or a graded potential (GP) synapse but not both. This study investigated how signals passed the glutamatergic synapse between the rod photoreceptor and its postsynaptic hyperpolarizing bipolar cells (HBCs) and light responses of retinal neurons with dual-cell and single-cell patch-clamp recording techniques. The results showed that scotopic lights evoked GPs in rods, whose depolarizing Phase 3 associated with the light offset also evoked APs of a duration of 241.8 ms and a slope of 4.5 mV/ms. The depolarization speed of Phase 3 (Speed) was 0.0001–0.0111 mV/ms and 0.103–0.469 mV/ms for rods and cones, respectively. On pairs of recorded rods and HBCs, only the depolarizing limbs of square waves applied to rods evoked clear currents in HBCs which reversed at −6.1 mV, indicating cation currents. We further used stimuli that simulated the rod light response to stimulate rods and recorded the rod-evoked excitatory current (rdEPSC) in HBCs. The normalized amplitude (R/Rmax), delay, and rising slope of rdEPSCs were differentially exponentially correlated with the Speed (all p < 0.001). For the Speed < 0.1 mV/ms, R/Rmax grew while the delay and duration reduced slowly; for the Speed between 0.1 and 0.4 mV/ms, R/Rmax grew fast while the delay and duration dramatically decreased; for the Speed > 0.4 mV/ms, R/Rmax reached the plateau, while the delay and duration approached the minimum, resembling digital signals. The rdEPSC peak was left-shifted and much faster than currents in rods. The scotopic-light-offset-associated major and minor cation currents in retinal ganglion cells (RGCs), the gigantic excitatory transient currents (GTECs) in HBCs, and APs and Phase 3 in rods showed comparable light-intensity-related locations. The data demonstrate that the rod-HBC synapse is a perfect synapse that can differentially decode and code analog and digital signals to process enormously varied rod and coupled-cone inputs.

Early cancer detection is the key to a positive clinical outcome. While a number of early diagnostics methods exist in clinics today, they tend to be invasive and limited to a few cancer types. Thus, a clear need exists for non-invasive diagnostics methods that can be used to detect the presence of cancer of any type. Liquid biopsy based on analysis of molecular components of peripheral blood has shown significant promise in such pan-cancer diagnostics; however, existing methods based on this approach require improvements, especially in sensitivity of early-stage cancer detection. The improvement would likely require diagnostics assays based on multiple different types of biomarkers and, thus, calls for identification of novel types of cancer-related biomarkers that can be used in liquid biopsy. Whole-blood transcriptome, especially its non-coding component, represents an obvious yet under-explored biomarker for pan-cancer detection. In this study, we show that whole transcriptome analysis using RNA-seq could indeed serve as a viable biomarker for pan-cancer detection. Furthermore, a class of long non-coding (lnc) RNAs, very long intergenic non-coding (vlinc) RNAs, demonstrated superior performance compared with protein-coding mRNAs. Finally, we show that age and presence of non-blood cancers change transcriptome in similar, yet not identical, directions and explore implications of this observation for pan-cancer diagnostics.

ObjectiveTo evaluate the prediction performance of 18F-PSMA-1007 PET/CT and clinicopathologic characteristics on prostate cancer (PCa) risk stratification and distant metastatic prediction.Materials and MethodsA retrospective analysis was performed on 101 consecutively patients with biopsy or radical prostatectomy proved PCa who underwent 18F-PSMA-1007 PET/CT. The semi-quantitative analysis provided minimum, maximum and mean standardized uptake (SUVmin, SUVmax and SUVmean) of PCa. Association between clinicopathologic characteristics (total prostate-specific antigen, tPSA and Gleason Score, GS) and PET/CT indexes were analyzed. The diagnostic performance of distant metastatic on PET/CT parameters, tPSA and GS was evaluated using logistic regression analyses. A path analysis was conducted to evaluate the mediating effect of tPSA level on the relation between semi-quantitative parameters of primary tumors and metastatic lesions.ResultsThe PET/CT parameters were all higher in high risk stratification subgroups (tPSA>20 ng/mL, GS ≥ 8, and tPSA>20 ng/mL and/or GS ≥ 8, respectively) with high sensitivity (86.89%, 90.16% and 83.61%, respectively). The SUVmax, tPSA and GS could effectively predict distant metastatic with high sensitivity of SUVmax (90.50%) compared with tPSA (57.14%) and GS (55.61%). With a cutoff value of 29.01ng/mL for tPSA, the detection rate of distant metastasis between low and high prediction tPSA group had statistical differences (50.00% vs. 76.60%, respectively; P = 0.006) which was not found on guideline tPSA level (P>0.05). 6/15 (40%) patients tPSA between 20ng/mL to 29.01ng/mL without distant metastases may change the risk stratification. Finally, tPSA had a partial mediating effect on SUVmax of primary tumors and metastases lesions.ConclusionThe 18F-PSMA-1007 PET/CT SUVmax has a higher sensitivity and can be an “imaging biomarker” for primary PCa risk stratification. The prediction tPSA level (29.01 ng/mL) is more conducive to the assessment of distant metastasis and avoid unnecessary biopsy.

Zooplankton bodies are organic-rich micro-environments that support fast bacterial growth. Therefore, the abundance of zooplankton-associated bacteria is much higher than that of free-living bacteria, which has profound effects on the nutrient cycling of freshwater ecosystems. However, a detailed analysis of associated bacteria is still less known, especially the relationship between those bacteria and bacterioplankton. In this study, we analyzed the relationships between Brachionus calyciflorus-associated bacterial and bacterioplankton communities in freshwater using high-throughput sequencing. The results indicated that there were significant differences between the two bacterial communities, with only 29.47% sharing OTUs. The alpha diversity of the bacterioplankton community was significantly higher than that of B. calyciflorus-associated bacteria. PCoA analysis showed that the bacterioplankton community gathered deeply, while the B. calyciflorus-associated bacterial community was far away from the whole bacterioplankton community, and the distribution was relatively discrete. CCA analysis suggested that many environmental factors (T, DO, pH, TP, PO43-, NH4+, and NO3-) regulated the community composition of B. calyciflorus-associated bacteria, but the explanatory degree of variability was only 37.80%. High-throughput sequencing revealed that Raoultella and Delftia in Proteobacteria were the dominant genus in the B. calyciflorus-associated bacterial community, and closely related to the biodegradation function. Moreover, several abundant bacterial members participating in carbon and nitrogen cycles were found in the associated bacterial community by network analysis. Predictive results from FAPROTAX showed that the predominant biogeochemical cycle functions of the B. calyciflorus-associated bacterial community were plastic degradation, chemoheterotrophy, and aerobic chemoheterotrophy. Overall, our study expands the current understanding of zooplankton–bacteria interaction and promotes the combination of two different research fields.

Small molecular nucleic acid drugs produce antiviral effects by activating pattern recognition receptors (PRRs). In this study, a small molecular nucleotide containing 5′triphosphoric acid (5′PPP) and possessing a double-stranded structure was designed and named nCoV-L. nCoV-L was found to specifically activate RIG-I, induce interferon responses, and inhibit duplication of four RNA viruses (Human enterovirus 71, Human poliovirus 1, Human coxsackievirus B5 and Influenza A virus) in cells. In vivo, nCoV-L quickly induced interferon responses and protected BALB/c suckling mice from a lethal dose of the enterovirus 71. Additionally, prophylactic administration of nCoV-L was found to reduce mouse death and relieve morbidity symptoms in a K18-hACE2 mouse lethal model of SARS-CoV-2. In summary, these findings indicate that nCoV-L activates RIG-I and quickly induces effective antiviral signals. Thus, it has potential as a broad-spectrum antiviral drug.

Isotactic polybutene (iPB) has a wide application in the water pipe field. However, the most valuable form I, needs 7 days to complete the transformation. In this study, the attapulgite (ATP), which produces lattice matching of the iPB form I, was selected to prepare an iPB/ATP composite. The Fischer–Tropsch wax (FTW) was grafted with maleic anhydride to obtain MAFT, and the ATP structure was reset by reactions with MAFT to the prepared FATP, which improved the interface compatibility of the ATP and iPB. The Fourier transform infrared spectroscopy (FT-IR) and the water contact angle test confirmed the successful synthesis of FATP. X-ray diffraction (XRD) verified that the graft of MAFT did not affect the crystal structure of ATP. The iPB + 5% FATP had the maximum flexural strength, which was 12.45 Mpa, and the flexural strength of the iPB + 5% FATP annealing for 1 day was much higher than others. Scanning electron microscope (SEM) photographs verified that FATP and iPB had good interface compatibility. The crystal transformation behavior indicated that the iPB + 5% FATP had the fastest crystal transformation rate, which proved that the reset structure, ATP, greatly accelerated the crystal transformation of iPB. This was a detailed study on the effect of lattice matching, interfacial compatibility and internal lubrication of the reset structure, ATP, in the nucleation and growth stages of iPB form I. The result was verified by XRD, differential scanning calorimetry (DSC), Avrami kinetics and polarizing microscope (POM) analysis.

Second near-infrared (NIR-II) fluorescence imaging shows huge application prospects in clinical disease diagnosis and surgical navigation, while it is still a big challenge to exploit high performance NIR-II dyes with long-wavelength absorption and high fluorescence quantum yield. Herein, based on planar pconjugated donor-acceptor-donor systems, three NIR-II dyes (TP-DBBT, TP-TQ1, and TP-TQ2) were synthesized with bulk steric hindrance, and the influence of acceptor engineering on absorption/emission wavelengths, fluorescence efficiency and photothermal properties was systematically investigated. Compared with TP-DBBT and TP-TQ2, the TP-TQ1 based on 6,7-diphenyl-[1,2,5]thiadiazoloquinoxaline can well balance absorption/emission wavelengths, NIR-II fluorescence brightness and photothermal effects. And the TP-TQ1 nanoparticles (NPs) possess high absorption ability at a peak absorption of 877 nm, with a high relative quantum yield of 0.69% for large steric hindrance hampering the close π-π stacking interactions. Furthermore, the TP-TQ1 NPs show a desirable photothermal conversion efficiency of 48% and good compatibility. In vivo experiments demonstrate that the TP-TQ1 NPs can serve as a versatile theranostic agent for NIR-II fluorescence/photoacoustic imaging-guided tumor phototherapy. The molecular planarization strategy provides an approach for designing efficient NIR-II fluorophores with extending absorption/emission wavelength, high fluorescence brightness, and outstanding phototheranostic performance. [ABSTRACT FROM AUTHOR]

Herein, a novel and facile organic photosensitizer (thioxanthone)-mediated energy-transfer-enabled (EnT-enabled) dearomative [2+2] cycloaddition of aromatic heterocycles/maleimides for green synthesis of cyclobutane-fused polycyclic skeletons is reported. Mechanistic investigations revealed that different EnT pathways by triplet thioxanthone were initiated when different aromatic heterocycles participated in the reaction, giving the corresponding excited intermediates, which underwent the subsequent intermolecular [2+2] cycloaddition to access the desired highly functionalized cyclobutane-fused polycyclic skeletons. [ABSTRACT FROM AUTHOR]

To suppress random vibration of aircraft models during wind tunnel tests, a novel magnetorheological elastomer (MRE)-based device with variable stiffness and variable damping (VSVD) is proposed, which is installed on the tail support system. Firstly, the dynamic characteristics of the tail support system are established using finite element model simulation to obtain the vibration mode and stress distribution. Next, the vibration reduction mechanism of the MRE-based tail support system is analyzed by solving a finite element model. Then, the magnetic-controlled VSVD device with an annular sandwich structure is proposed, and the decisive rheology material and structural parameters in relation to the tail support system's dynamics are determined. Subsequently, the magnetically generated element with multicoils is designed to guarantee a large enough magnetic field, and the optimal structure parameters are obtained. Finally, random wind flow experiments in the wind tunnel and frequency sweep tests in the ground laboratory for the tail support system equipped on the VSVD device are conducted to verify the effectiveness of the proposed device, respectively. The results under 15-200 Hz random excitation indicate the root mean square of acceleration at the centroid of the aircraft model with the VSVD device can be decreased by 46.8% compared to the system without the VSVD device. [ABSTRACT FROM AUTHOR]

Introduction: Insulin resistance (IR) is a feature of metabolic syndrome and plays an important role in cognitive impairment (CI). The triglyceride-glucose (TyG) index is a convenient and cost-effective surrogate for assessing IR. This study aimed to assess the association between the TyG index and CI. Methods: This community population-based cross-sectional study used a cluster-sampling methodology. All participants underwent the education-based Mini-Mental State Examination (MMSE), and those with CI were identified using standard thresholds. The fasting blood triglyceride and glucose levels were measured in the morning, and the TyG index was calculated as ln (½ fasting triglyceride level [mg/dL] × fasting blood glucose level [mg/dL]). Multivariable logistic regression and subgroup analysis were used to assess the relationship between the TyG index and CI. Results: This study included 1484 subjects, of which 93 (6.27%) met the CI criteria. Multivariable logistic regression showed that CI incidence increased by 64% per unit increase in the TyG index (odds ratio [OR] = 1.64, 95% confidence interval [CI]: 1.02-2.63, p = 0.042). CI risk was 2.64-fold higher in the highest TyG index quartile compared to the lowest TyG index quartile (OR = 2.64, 95% CI: 1.19-5.85, p = 0.016). Finally, interaction analysis showed that sex, age, hypertension, and diabetes did not significantly affect the association between the TyG index and CI. Conclusion: The present study suggested that an elevated TyG index was associated with a higher CI risk. Subjects with a higher TyG index should manage and treat at an early stage to alleviate the cognitive decline. [ABSTRACT FROM AUTHOR]

From the perspective of the Internet, this article focuses on semantic selection in translation, and delves into the semantic selection of translation in Morris' modern semiotic theory. After exploring the relevant theoretical concepts by dimensions, it is found that the semantics of translation in Morris' modern semiotic theory can be divided into three types: denotational semantics, pragmatic semantics and intra-verbal semantics. Finally, the choice of the three types of semantics: denotational semantics, pragmatic semantics and intra-verbal semantics is explored in depth to provide guidance for related theoretical research. [ABSTRACT FROM AUTHOR]

Coxsackievirus A16 (CA16) has caused worldwide epidemics of hand, foot and mouth disease (HFMD), particularly in infants and pre-school children. Currently, there are no vaccines or antiviral drugs available for CA16-associated disease. In this study, a CA16-specific monoclonal antibody (MAb) NA11F12 was derived with an epidemic CA16 strain (GenBank no. JX127258). NA11F12 was found to have high cross-neutralization activity against different CA16 subgenotypes but not EV71 using RD cells. The neutralizing titers of NA11F12 ranged from 1:1024 to 1:12288 against A, B1, B2 and C subgenotypes of CA16 and was less than 8 against EV71 strain. In the neonatal mouse model, a single treatment of NA11F12 showed effective protection with a dose- and time-dependent relationship against lethal challenge by CA16 strain (GenBank no. JX481738). At day 1 post-infection, administering more than 0.1 μg/g of NA11F12 could protect 100% newborn mice from mobility and mortality challenged by CA16. With dose of 10 μg/g of NA11F12, a single administration fully protected mice against CA16-associated disease within 4 days post-infection. And there were 80% and 60% mice protected by administering NA11F12 at day 5 post-infection and day 6 post-infection when the control mice had shown clinical symptoms for 1- and 2-day, respectively. Immunohistochemical and histological analysis confirmed that NA11F12 significantly prohibited CA16 VP1 expression in various tissues and prevented CA16-induced necrosis. In conclusion, a CA16-specific MAb NA11F12 with high cross-neutralization activity was identified, which could effectively protect lethal CA16 challenge in mice. It could be a potential therapeutic MAb against CA16 in the future.

Abstract Background Early identification of noninvasive ventilation (NIV) failure is a promising strategy for reducing mortality in chronic obstructive pulmonary disease (COPD) patients. However, a risk-scoring system is lacking. Methods To develop a scale to predict NIV failure, 500 COPD patients were enrolled in a derivation cohort. Heart rate, acidosis (assessed by pH), consciousness (assessed by Glasgow coma score), oxygenation, and respiratory rate (HACOR) were entered into the scoring system. Another two groups of 323 and 395 patients were enrolled to internally and externally validate the scale, respectively. NIV failure was defined as intubation or death during NIV. Results Using HACOR score collected at 1–2 h of NIV to predict NIV failure, the area under the receiver operating characteristic curves (AUC) was 0.90, 0.89, and 0.71 for the derivation, internal-validation, and external-validation cohorts, respectively. For the prediction of early NIV failure in these three cohorts, the AUC was 0.91, 0.96, and 0.83, respectively. In all patients with HACOR score > 5, the NIV failure rate was 50.2%. In these patients, early intubation (

Abstract. Background:. In China, upper airway cough syndrome (UACS) is only less frequent than cough-variant asthma and accounts for 24.71% of chronic cough. This study aimed to determine the pathogenetic constituents and factors affecting UACS in children of different age groups, and to identify clinical clues for diagnosing UACS and a method for curative effect evaluation. Methods:. A total of 103 children with UACS whose chief complaint was chronic cough were studied from January to November 2013 at Children's Hospital, Capital Institute of Pediatrics. According to their age, children with UACS were divided into 3 groups: nursing children, pre-school children, and school-age children. We analyzed the differences in pathogenetic constituents and factors affecting UACS in children. The effect of UACS treatment was evaluated by the visual analog scale (VAS) and an objective examination. Chi-squared test and analysis of variance were performed with the SPSS 19.0 statistical software. Results:. There was a high incidence of UACS in school-age children. Rhinitis with adenoid hypertrophy was the main cause of 103 suspected UACS cases. Adenoidal hypertrophy was the major cause of UACS in the pre-school children group, while rhinitis was the major reason in the nursing children and school-age children groups. Among the 103 children, there were 45 allergen-positive children, with no significant difference among different age groups. VAS scores in the different disease groups after treatment were lower than those before treatment (all P

China’s BDS-3 global navigation satellite system has been built and is providing official open Positioning, Navigation, and Timing (PNT) service with full operational capability (FOC) since July 2020. The main new civil B1C and B2a ranging code signals are broadcasted on the two carriers with central frequencies of 1575.42 MHz and 1176.45 MHz, which were shared by other GNSSs. Compared with traditional signals, such as GPS L1 C/A and BDS B1I, the new civil signals have better modulation and wider bandwidth to be expected to achieve a better range performance. In order to evaluate code ranging accuracies directly, a zero-baseline experiment using a geodetic GNSS antenna and a four-channel intermediate frequency (IF) signal recorder was conducted. Two channels were used to receive the signals with a central frequency of 1575.42 MHz at a 62 MHz sampling rate, and the other two channels are for 1176.45 MHz. The raw IF data were post-processed using a software-defined receiver (SDR) to compute the code signal path differences between two channels with the same frequencies. Compared with the traditional hardware receiver, SDR has the characteristics of flexible use and good operability, but its running speed is slow. The root-mean-square (RMS) and bias values of the path differences from BDS B1C, BDS B2a, and GPS L5C were used to evaluate their accuracies. The results show that there is a weak negative correlation between the satellite elevation and the ranging accuracy when the satellite elevation ranges from 30° to 90°. The ranging accuracy of the B1C signal is lower than that of B2a, which may be caused by different code rates, bandwidth, and signal structure. The GPS L5C is used for precision analysis as a comparison. It shows that the code signal path differences accuracy of L5C is close to the B2a.

Dye adsorption by magnetic modified biochar has now received growing interest due to its excellent adsorption performance and facile separation for recycling. In this study, nano iron oxide–modified biochar was fabricated via the successive hydrothermal-pyrolyzing method using Chlorella vulgaris (Cv) and FeSO4·7H2O as raw materials, and its adsorption on Rhodamine B (RhB) in aqueous solution was studied. Multiple techniques such as X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), Brunauer–Emmett–Teller (BET), vibrating sample magnetometry (VSM) and X-ray photoelectron spectroscopy (XPS) were employed to comprehensively characterize the structure, morphology and physicochemical properties of the adsorbent. The as-synthesized nano iron oxide–modified biochar (CBC-Fe(II)) exhibited a large surface area (527.6 m2/g) and high magnetic saturation value (13.7 emu/g) to facilitate magnetic separation. Compared with CBC and CBC-Fe(III), CBC-Fe(II) exhibited superior adsorption ability towards RhB in aqueous solution, with a maximum adsorption capacity of 286.4 mg/g. The adsorption process of RhB onto CBC-Fe(II) was well described by the pseudo-second-order kinetic model and Langmuir isotherm model, indicating monolayer chemisorption behaviors for the adsorption system. Facile preparation, great adsorption performance and magnetic recovery properties endow CBC-Fe(II) to be a promising adsorbent for dye removal.

Coxsackievirus A6 (CV-A6) is one of pathogens causing hand, foot and mouth disease (HFMD) and becomes a new challenge to HFMD control. In this study, we first built a single-round pseudovirus infection system for CV-A6, and then developed a pseudovirus luciferase assay (PVLA) for anti-CV-A6 neutralizing antibody (NtAb) quantification. Since cytopahtic effect (CPE) is considered as the gold standard test for anti-enterovirus NtAb detection, a comparison study has been performed using 318 clinical serum samples, as measured both by PVLA and CPE. The sensitivity and specificity of PVLA was 94.9% (95% CI between 90.8–97.5%) and 92.7% (95% CI between 86.6–96.6%), respectively. Statistical analysis revealed that PVLA and CPE were highly correlated (spearman r = 0.931, P

The world has entered the second wave of the COVID-19 pandemic, and its intensity is significantly higher than that of the first wave of early 2020. Many countries or regions have been forced to start the second round of lockdowns. To respond rapidly to this global pandemic, dozens of COVID-19 vaccine candidates have been developed and many are undergoing clinical testing. Evaluating and defining effective vaccine candidates for human use is crucial for prioritizing vaccination programs against COVID-19. In this review, we have summarized and analyzed the efficacy, immunogenicity and safety data from clinical reports on different COVID-19 vaccines. We discuss the various guidelines laid out for the development of vaccines and the importance of biological standards for comparing the performance of vaccines. Lastly, we highlight the key remaining challenges, possible strategies for addressing them and the expected improvements in the next generation of COVID-19 vaccines.

Soil organic carbon (SOC) is an important component of the carbon (C) cycle in forest ecosystems, and is largely influenced by tree species. Leaf litter originated from different vegetations introduce organic materials into soil with different quantities and qualities, and influence the formation and stability of soil C pool. We present a study on the influence of tree species on SOC stability under three temperate forests: pine (Pinus tabuliformis Carr.), larch (Larix principis-rupprechtii Mayr.) and birch (Betula dahurica Pall.) in the Baihua Mountain Reserve. The SOC and permanganate oxidizable C (POXC) concentrations in the 0–5, 5–10, 10–20 and 20–30 cm soil layers were determined. The SOC stability was evaluated by analyzing the chemical composition of SOC and the distribution of organic C in soil particle-size fractions under different tree species. The birch forest had significantly higher SOC and POXC concentrations than pine and larch in all the four soil layers. These differences might be partly related to the altitude, and also caused by the differences in litter characteristics between birch and the two coniferous species. The organic C was enriched in clay-sized fraction in birch forest soil, but showed higher concentrations in coarse sand fraction (2000-250 μm) under pine, suggesting a higher potential of birch forest for C accumulation in stable SOC pools. The chemical composition of SOC was determined by solid-state 13C nuclear magnetic resonance (NMR) spectra and showed that the birch forest soil had higher alkyl C/O-alkyl C, aromatic C/O-alkyl C and hydrophobic C/hydrophilic C ratios than pine and larch forest soils in the top 5 cm soil layer, reflecting a more recalcitrant SOC composition under birch than under pine and larch. We concluded that the birch forest could not only increase SOC concentration in mineral soils but also had a higher potential to accumulate C in stable soil C pools, and thus is more beneficial to SOC stabilization than the pine and larch forests. This study highlights that future strategy of tree species selection needs to consider the potential effects of tree species on the stability in addition to the concentration of SOC.

Background: Pregnancy-specific vitamin reference ranges are currently not available for maternal vitamin management during pregnancy. This study aimed to propose pregnancy-specific vitamin reference ranges and to investigate the factors influencing vitamin levels during pregnancy.Methods: A cross-sectional study that included pregnant women from 17 cities in 4 provinces in western China was conducted from 2017 to 2019. A total of 119,286 subjects were enrolled in the study. Serum vitamin A, vitamin D, and vitamin E levels were measured. A multivariable linear regression model and restricted cubic spline function were used to analyze the factors related to vitamin levels.Results: The reference ranges for vitamin A, D, and E levels were 0.22–0.62 mg/L, 5–43 ng/mL, and 7.4–23.5 mg/L, respectively. A linear relationship was found between vitamin E level and age (β = 0.004; 95% confidence interval [CI], 0.0037–0.0042; p < 0.001), and a nonlinear relationship was found between vitamin D (p nonlinear = 0.033) and vitamin A levels and age (p nonlinear < 0.001). Season, gestational trimester, and regions were related to the levels of the three vitamins in the multivariable models (p < 0.05).Conclusions: The lower limit of vitamin A during pregnancy was the same as the reference value currently used for the general population. The reference ranges of vitamins D and E during pregnancy were lower and higher, respectively, than the currently used criteria for the general population. Vitamin A, D, and E levels differed according to age, season, gestational trimester, and region.

Current advances in next-generation sequencing techniques have allowed researchers to conduct comprehensive research on the microbiome and human diseases, with recent studies identifying associations between the human microbiome and health outcomes for a number of chronic conditions. However, microbiome data structure, characterized by sparsity and skewness, presents challenges to building effective classifiers. To address this, we present an innovative approach for distance-based classification using mixture distributions (DCMD). The method aims to improve classification performance using microbiome community data, where the predictors are composed of sparse and heterogeneous count data. This approach models the inherent uncertainty in sparse counts by estimating a mixture distribution for the sample data and representing each observation as a distribution, conditional on observed counts and the estimated mixture, which are then used as inputs for distance-based classification. The method is implemented into a k-means classification and k-nearest neighbours framework. We develop two distance metrics that produce optimal results. The performance of the model is assessed using simulated and human microbiome study data, with results compared against a number of existing machine learning and distance-based classification approaches. The proposed method is competitive when compared to the other machine learning approaches, and shows a clear improvement over commonly used distance-based classifiers, underscoring the importance of modelling sparsity for achieving optimal results. The range of applicability and robustness make the proposed method a viable alternative for classification using sparse microbiome count data. The source code is available at https://github.com/kshestop/DCMD for academic use.

Background Previous studies have suggested that sleep timing is associated with cardiovascular risk factors. However, there is no evidence on the relationship between sleep timing and congestive heart failure (CHF). We aimed to examine this relationship in this study. Methods and Results We recruited 4765 participants (2207 men; mean age, 63.6±11.0 years) from the SHHS (Sleep Heart Health Study) database in this multicenter prospective cohort study. Follow‐up was conducted until the first CHF diagnosis between baseline and the final censoring date. Sleep timing (bedtimes and wake‐up times on weekdays and weekends) was based on a self‐reported questionnaire. Cox proportional hazard models were constructed to investigate the association between sleep timing and CHF. During the mean follow‐up period of 11 years, 519 cases of CHF (10.9%) were reported. The multivariable Cox proportional hazards models revealed that participants with weekday bedtimes >12:00 am (hazard ratio [HR], 1.56; 95% CI, 1.15–2.11; P=0.004) and from 11:01 pm to 12:00 am (HR, 1.25; 95% CI, 1.00–1.56; P=0.047) had an increased risk of CHF compared with those with bedtimes from 10:01 pm to 11:00 pm. After stratified analysis, the association was intensified in participants with a self‐reported sleep duration of 6 to 8 hours. Furthermore, wake‐up times >8:00 am on weekdays (HR, 1.53; 95% CI, 1.07–2.17; P=0.018) were associated with a higher risk of incident CHF than wake‐up times ≤6:00 am. Conclusions Delayed bedtimes (>11:00 pm) and wake‐up times (>8:00 am) on weekdays were associated with an increased risk of CHF.