Safety and immunogenicity of a modified Omicron-adapted inactivated vaccine in healthy adults: a randomized, double-blind, active-controlled Phase III clinical trial

BackgroundUpdated vaccine strategies are needed to protect against new SARS-CoV-2 variants with increased immune escape. Here, information on the safety and immunogenicity of an inactivated Omicron-adapted vaccine is presented, as compared with CoronaVac.MethodsA randomized, double-blind, active-controlled, phase III clinical trial was conducted to compare a modified Omicron-adapted vaccine (Omicron vaccine) with the authorized prototype vaccine (CoronaVac®) as a booster dose. Healthy adults aged ≥18 years, who have previously received 2 or 3 doses of CoronaVac (2C or 3C cohort) at least 6 months before, were enrolled to get a booster dose of Omicron vaccine or CoronaVac in a ratio of 2:1 (2C/3C+1O/1C). Back-up serums after two initial doses of CoronaVac (2C+0) for adults aged 26-45 years were collected from a previous study. Immunogenicity and safety data at 28 days after vaccination were collected and analyzed. One of the primary objectives was to evaluate the superiority of immunogenicity of Omicron vaccine booster against Omicron BA.1, compared with CoronaVac booster against BA.1. Another objective was to evaluate the non-inferiority of immunogenicity of Omicron vaccine booster against BA.1, compared with two initial doses of CoronaVac against ancestral strain.ResultsBetween June 1st and July 21st, 2022, a total of 1,500 healthy adults were enrolled. Results show that all pre-specified superiority criteria for BA.1 neutralizing antibody were met. Specifically, within the 3C cohort (3C+1O vs. 3C+1C), the geometric mean titers’ (GMT) ratio and 95% confidence interval (CI) was 1.64 (1.42, 1.89), with the lower 95%CI ≥1; a GMT ratio of 1.84 (1.57, 2.16) was observed for 2C+1O versus 3C+1C. For seroconversion rate, the lower 95%CIs of differences between immuno-comparative groups (2/3C+1O vs. 3C+1C) were all above the superiority criterion 0%. However, the non-inferiority criterion of the lower 95%CI of GMT ratio ≥2/3 was unfulfilled for 2C/3C+1O against BA.1 versus 2C+0 against ancestral strain. Safety profiles were similar between groups, with no safety concerns identified.ConclusionThe Omicron-adapted vaccine was well-tolerated and could elicit superior immune responses as compared with CoronaVac against Omicron, while it appeared inferior to CoronaVac against ancestral strain.Clinical trial registrationhttps://classic.clinicaltrials.gov/ct2/show/NCT05381350?term=NCT05381350&draw=2&rank=1, identifier NCT05381350

Gab2 Ablation Reverses the Stemness of HER2-Overexpressing Breast Cancer Cells

Background/Aims: HER2 has been implicated in mammary tumorigenesis as well as aggressive tumor growth and metastasis. Its overexpression is related to a poor prognosis and chemoresistance in breast cancer patients. Although Grb2-associated binding protein 2 (Gab2) is important in the development and progression of human cancer, its effects and mechanisms in HER2-overexpressing breast cancer are unclear. Methods: Clone formation and MTT assays were used to examine cell proliferation. To detect the effect of Gab2 on the stemness of breast cancer cells, we used flow cytometry, a sphere formation assay, real-time PCR, and western blot. An animal model was created to validate the effect of Gab2 on tumor growth in vivo. Tissue slides were analyzed by immunohistochemistry. Results: Knockdown of Gab2 suppressed PI3K/AKT and MAPK/ERK pathway activity. Gab2 ablation also reduced the stemness of HER2-overexpressing breast cancer cells. In vivo, knockdown of Gab2 inhibited tumor growth. Conclusion: This study unveils a potential function of Gab2 in HER2-overexpressing breast cancer cells. Gab2 might be a potential target in the clinical therapy of HER2-overexpressing breast carcinoma

A New Class of Difference Methods with Intrinsic Parallelism for Burgers–Fisher Equation

This paper proposes a new class of difference methods with intrinsic parallelism for solving the Burgers–Fisher equation. A new class of parallel difference schemes of pure alternating segment explicit-implicit (PASE-I) and pure alternating segment implicit-explicit (PASI-E) are constructed by taking simple classical explicit and implicit schemes, combined with the alternating segment technique. The existence, uniqueness, linear absolute stability, and convergence for the solutions of PASE-I and PASI-E schemes are well illustrated. Both theoretical analysis and numerical experiments show that PASE-I and PASI-E schemes are linearly absolute stable, with 2-order time accuracy and 2-order spatial accuracy. Compared with the implicit scheme and the Crank–Nicolson (C-N) scheme, the computational efficiency of the PASE-I (PASI-E) scheme is greatly improved. The PASE-I and PASI-E schemes have obvious parallel computing properties, which show that the difference methods with intrinsic parallelism in this paper are feasible to solve the Burgers–Fisher equation

Numerical Simulation of Wind Turbine Aerodynamic Characteristics under Wind Shear Based on Lattice-Boltzmann Method

In order to study the influence of wind shear on the aerodynamic characteristics of large wind turbines, taking the 5MW wind turbine blade model published by NREL as the research object, large eddy simulation (LES) of wind turbines was carried out by using XFlow fluid simulation software based on Lattice-Boltzmann method (LBM). WALE turbulence model was used to study wind shear at 3, 11.2 and 25m/s wind speeds. The effect of factors on the axial thrust and torque of wind turbines is compared with the data published by NREL. The results show that the XFlow software based on LBM and LES method has good capturing ability for the eddy wake of wind turbine; wind shear causes the airfoil section of each section of blade to deviate from the best designed attack angle in theory and results in a decrease in torque applied to the wind turbine

A Nitrocellulose Paper-Based Multi-Well Plate for Point-of-Care ELISA

Low-cost diagnostic tools for point-of-care immunoassays, such as the paper-based enzyme-linked immunoassay (ELISA), have become increasingly important, especially so in the recent COVID-19 pandemic. ELISA is the gold-standard antibody/antigen sensing method. This paper reports an easy-to-fabricate nitrocellulose (NC) paper plate, coupled with a desktop scanner for ELISA, which provides a higher protein immobilization efficiency than the conventional cellulose paper-based ELISA platforms. The experiments were performed using spiked samples for the direct ELISA of rabbit IgG with a limit of detection (LOD) of 1.016 μg/mL, in a measurement range of 10 ng/mL to 1 mg/mL, and for the sandwich ELISA of sperm protein (SP-10) with an LOD of 88.8 ng/mL, in a measurement range of 1 ng/mL to 100 μg/mL. The described fabrication method, based on laser-cutting, is a highly flexible one-step laser micromachining process, which enables the rapid production of low-cost NC paper-based multi-well plates with different sizes for the ELISA measurements

A Low-Backpressure Single-Cell Point Constriction for Cytosolic Delivery Based on Rapid Membrane Deformations

Mechanically deforming biological cells through microfluidic constrictions is a recently introduced technique for the intracellular delivery of macromolecules possibly through transient membrane pores induced in the process. The technique is attractive for research and clinical applications mainly because it is simple, fast, and effective while being free of adverse effects often associated with well-known techniques that rely on field- or vector-based delivery. In this nascent approach, an utmost and crucial role is played by the constriction, often in rectangular profile, and it squeezes cells only in one dimension. The results achieved suggest that the longer the constriction is the higher the delivery performance. Contrary to this view, we demonstrate here a unique constriction profile that is highly localized (point) and yet returns comparably effective delivery. Point constrictions are of a semiround geometry, forcing cells in both dimensions while introducing very little backpressure to the system, which is a silicon-glass platform wherein constrictions are arranged in series along an array of channels. The influence of the constriction size and count as well as treatment pressure on delivery performance is presented on the basis of the flow-cytometric analyses of HCT116 cells treated using dextran as model molecules. Delivery performance is also presented for common mammalian cell lines including NIH 3T3, HEK293, and MDCK. Moreover, the versatility of the platform is demonstrated in gene knockdown experiments using synthetic siRNA as well as on the delivery of proteins. Target proteins in some cells exhibit nondiffusive distribution profile raising the plausibility of mechanisms other than transient membrane pores

Paper-Based All-in-One Origami Nanobiosensor for Point-of-Care Detection of Cardiac Protein Markers in Whole Blood

Rapid and accurate diagnosis of cardiovascular diseases (CVDs) at the earliest stage is of paramount importance to improve the treatment outcomes and avoid irreversible damage to a patient's cardiovascular system. Microfluidic paper-based devices (μPADs) represent a promising platform for rapid CVD diagnosis at the point of care (POC). This paper presents an electrochemical μPAD (E-μPAD) with an all-in-one origami design for rapid and POC testing of cardiac protein markers in whole blood. Based on the label-free, electrochemical impedance spectroscopy (EIS) immunoassay, the E-μPAD integrates all essential components on a single chip, including three electrochemical cells, a plasma separation membrane, and a buffer absorption pad, enabling easy and streamlined operations for multiplexed detection of three cardiac protein markers [cardiac troponin I (cTnI), brain natriuretic peptide (BNP)-32, and D-Dimer] on a finger-prick whole blood sample within 46 min. Superior analytical performance is achieved through sensitive EIS measurement on carbon electrodes decorated with semiconductor zinc oxide nanowires (ZnO NWs). Using spiked human plasma samples, ultralow limits of detection (LODs) of E-μPAD are achieved at 4.6 pg/mL (190 fM) for cTnI, 1.2 pg/mL (40 fM) for BNP-32, and 146 pg/mL (730 fM) for D-Dimer. Real human blood samples spiked with purified proteins are also tested, and the device's analytical performance was proven to be comparable to commercial ELISA kits. The all-in-one E-μPAD will allow rapid and sensitive testing of cardiac protein markers through easy operations, which holds great potential for on-site screening of acute CVDs in nonlaboratory settings such as emergency rooms, doctor's offices, or patient homes

Prediction of Unconfined Compression Strength for Saline-Alkaline Soils Mixed with Cement and Wheat Straw

A series of unconfined compression tests were performed to investigate the influence of wheat straws on the unconfined compression strength for saline-alkaline soils and saline-alkaline soils mixed with cement. In unconfined compression tests, 20 groups of soil specimens were prepared at five different percentages of wheat straws content (i.e., 0.0%, 0.1%, 0.15%, 0.2%, and 0.25% by weight of saline-alkaline soils) and four different percentages of cement content (i.e., 0%, 3%, 6%, and 9% by weight of saline-alkaline soils), and unconfined compression tests were carried out after 3-, 7-, 14-, 28-, and 56-day curing periods. Test results indicated that the inclusion of wheat straws within saline-alkaline soils and saline-alkaline soils mixed with cement leads to an increase in the unconfined compressive strength of specimens and also changed the brittle behavior to a more ductile one for specimens. In addition, based on the results from unconfined compression tests, a formula for predicting the unconfined compression strength of specimens related to cement content, wheat straw content, curing periods, etc., was determined, and comparing with the results from unconfined compression tests, it had higher precision in predicting the unconfined compression strength of specimens

Super‐Elastic Carbonized Mushroom Aerogel for Management of Uncontrolled Hemorrhage

Abstract Uncontrolled hemorrhage is still the most common cause of potentially preventable death after trauma in prehospital settings. However, there rarely are hemostatic materials that can achieve safely and efficiently rapid hemostasis simultaneously. Here, new carbonized cellulose‐based aerogel hemostatic material is developed for the management of noncompressible torso hemorrhage, the most intractable issue of uncontrolled hemorrhage. The carbonized cellulose aerogel is derived from the Agaricus bisporus after a series of processing, including cutting, carbonization, purification, and freeze‐drying. In vitro, the carbonized cellulose aerogels with porous structure show improved hydrophilicity, good blood absorption, and coagulation ability, rapid shape recoverable ability under wet conditions. And in vivo, the carbonized aerogels show effective hemostatic ability in both small and big animal serious hemorrhage models. The amount of blood loss and the hemostatic time of carbonized aerogels are all better than the positive control group. Moreover, the mechanism studies reveal that the good hemostatic ability of the carbonized cellulose aerogel is associated with high hemoglobin binding efficiency, red blood cell absorption, and platelets absorption and activation. Together, the carbonized aerogel developed in this study could be promising for the management of uncontrolled hemorrhage