Setting up a global SARS-CoV-2 surveillance system requires an understanding of how virus isolation and propagation practices, use of animal or human sera, and different neutralisation assay platforms influence assessment of SARS-CoV-2 antigenicity. In this study, with the contribution of 15 independent laboratories across all WHO regions, we carried out a controlled analysis of neutralisation assay platforms using the first WHO International Standard for antibodies to SARS-CoV-2 variants of concern (source: NIBSC). Live virus isolates (source: WHO BioHub or individual labs) or spike plasmids (individual labs) for pseudovirus production were used to perform neutralisation assays using the same serum panels.
View Article and Find Full Text PDFBackground: In humans and other mammals, the process of oogenesis initiates asynchronously in specific ovarian regions, leading to the localization of dormant and growing follicles in the cortex and medulla, respectively; however, the current understanding of this process remains insufficient.
Results: Here, we integrate single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) to comprehend spatial-temporal gene expression profiles and explore the spatial organization of ovarian microenvironments during early oogenesis in pigs. Projection of the germ cell clusters at different stages of oogenesis into the spatial atlas unveils a "cortical to medullary (C-M)" distribution of germ cells in the developing porcine ovaries.
Dual-atom catalysts (DACs) can be very effective for catalyzing both oxygen reduction reaction (ORR) and oxygen evolution reaction (OER). Herein, we present theoretical evidence of a new class of highly active DACs, namely, the double-atom embedded in nitrogen-doped graphene sheet 2M-N-C (M = Mn, Fe) on the basis of density functional theory calculations. Importantly, we find that the double active sites of 2M-N-C DACs entail an unconventional catalytic reaction pathway for ORR and OER.
View Article and Find Full Text PDFProtein aggregation causes a wide range of neurodegenerative diseases. Targeting and removing aggregates, but not the functional protein, is a considerable therapeutic challenge. Here, we describe a therapeutic strategy called "RING-Bait," which employs an aggregating protein sequence combined with an E3 ubiquitin ligase.
View Article and Find Full Text PDFDelivery of antisense oligonucleotides (ASOs) to airway epithelial cells is arduous due to the physiological barriers that protect the lungs and the endosomal entrapment phenomenon, which prevents ASOs from reaching their intracellular targets. Various delivery strategies involving peptide-, lipid-, and polymer-based carriers are being investigated, yet the challenge remains. S10 is a peptide-based delivery agent that enables the intracellular delivery of biomolecules such as GFP, CRISPR-associated nuclease ribonucleoprotein (RNP), base editor RNP, and a fluorescent peptide into lung cells after intranasal or intratracheal administrations to mice, ferrets, and rhesus monkeys.
View Article and Find Full Text PDFCoastal aquaculture ponds represented a biogeochemical hotspot in the global carbon cycle. However, there was a limited understanding of their dynamics. In this study, the eddy covariance (EC) technique was applied to quantify the net ecosystem CO exchange (NEE) over coastal aquaculture ponds in the Liaohe River estuary in northern China during 2020, aiming to investigate and quantify the carbon exchange characteristics of this region.
View Article and Find Full Text PDFImmune checkpoint inhibitors are standard-of-care for the treatment of advanced melanoma, but their use is limited by immune-related adverse events. Proteomic analyses and multiplex cytokine and chemokine assays from serum at baseline and at the adverse event onset indicated aberrant T cell activity with differential expression of type I and III immune signatures. This was in line with the finding of an increase in the proportion of CD4 T cells with IL-17A expression at the adverse event onset in the peripheral blood using flow cytometry.
View Article and Find Full Text PDFBoth protein nanoparticle and mRNA vaccines were clinically de-risked during the COVID-19 pandemic. These vaccine modalities have complementary strengths: antigen display on protein nanoparticles can enhance the magnitude, quality, and durability of antibody responses, while mRNA vaccines can be rapidly manufactured and elicit antigen-specific CD4 and CD8 T cells. Here we leverage a computationally designed icosahedral protein nanoparticle that was redesigned for optimal secretion from eukaryotic cells to develop an mRNA-launched nanoparticle vaccine for SARS-CoV-2.
View Article and Find Full Text PDFBackground: The aim of this study was to create a molecular diagnostic platform and establish a diagnostic pipeline for patients highly suspected of mitochondrial disorders. The effectiveness of three methods, namely, traditional restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR), Sanger sequencing for hotspot detection and whole mitochondrial DNA (mtDNA), and third-generation (Nanopore) whole mtDNA sequencing, will be compared in diagnosing patients with suspected primary mitochondrial diseases (PMDs). The strengths and limitations of different methods are also discussed.
View Article and Find Full Text PDFEvidence has demonstrated that exoskeleton robots can improve intestinal function in patients with spinal cord injury (SCI). However, the underlying mechanisms remain unelucidated. This study investigated the effects of exoskeleton-assisted walking (EAW) on intestinal function and intestinal flora structure in T2-L1 motor complete paraplegia patients.
View Article and Find Full Text PDFDeveloping high-power laser technology and its applications necessitates improvements in the laser-irradiation resistance of liquid-crystal modulation devices. In this study, the thermal characteristics of substrate and electrode materials, including sapphire-substrate indium tin oxide (ITO) electrodes, K9 glass-substrate ITO electrodes, sapphire-substrate gallium nitride (GaN) electrodes, and liquid-crystal optical switches, are investigated using simulation and experimental methods. Results show that the sapphire-substrate GaN electrode demonstrates the best heat dissipation and that the maximum temperature at the center of the spot under 75 W laser irradiation is 319 K, 52 K lower than that of an equally thick sapphire-substrate ITO electrode and 225 K lower than that of an equally thick K9 glass-substrate ITO electrode (steady state and test time >2min).
View Article and Find Full Text PDFPhotoactivatable (PA) rhodamine dyes are widely used in single-molecule tracking (SMT) and a variety of other fluorescence-based imaging modalities. One of the most commonly employed scaffolds uses a diazoketone to lock the rhodamine in the nonfluorescent closed form, which can be activated with 405 nm light. However, poor properties of previously reported dyes require significant washing, which can be resource- and cost-intensive, especially when performing microscopy in a large scale and high-throughput fashion.
View Article and Find Full Text PDFWe report the measurement of the inclusive cross sections for e^{+}e^{-}→nOCH (where nOCH denotes non-open charm hadrons) with improved precision at center-of-mass (c.m.) energies from 3.
View Article and Find Full Text PDFThe unique virus-cell interaction in Epstein-Barr virus (EBV)-associated malignancies implies targeting the viral latent-lytic switch is a promising therapeutic strategy. However, the lack of specific and efficient therapeutic agents to induce lytic cycle in these cancers is a major challenge facing clinical implementation. We develop a synthetic transcriptional activator that specifically activates endogenous BZLF1 and efficiently induces lytic reactivation in EBV-positive cancer cells.
View Article and Find Full Text PDFDeveloping an effective mRNA therapeutic often requires maximizing protein output per delivered mRNA molecule. We previously found that coding sequence (CDS) design can substantially affect protein output, with mRNA variants containing more optimal codons and higher secondary structure yielding the highest protein outputs due to their slow rates of mRNA decay. Here, we demonstrate that CDS-dependent differences in translation initiation and elongation rates lead to differences in translation- and deadenylation-dependent mRNA decay rates, thus explaining the effect of CDS on mRNA half-life.
View Article and Find Full Text PDFThree samples whose growth temperatures were 450°C, 500°C, and 560°C for , , and , respectively, were tested by femto-second time-resolved transient absorption spectroscopy. The results indicate that the carrier dynamics of excited state absorption were dominant, and the lifetimes of carriers trapped by defect levels were about tens of pico-seconds. To further study the influence of carrier dynamics and recovery time of samples by ion-implantation, ions of 80 and 130 KeV were implanted into the samples with dose of 10/ .
View Article and Find Full Text PDFBackground Noninvasive evaluation of metabolic dysfunction-associated fatty liver disease (MAFLD) with multiparametric US is essential, but multicenter studies are lacking. Purpose To evaluate the ability of multiparametric US with attenuation imaging (ATI) and two-dimensional (2D) shear-wave elastography (SWE) for predicting metabolic dysfunction-associated steatohepatitis (MASH) in participants with MAFLD, regardless of hepatitis B virus infection status. Materials and Methods This prospective cross-sectional multicenter study of consecutive adults with MAFLD who underwent multiparametric US with ATI and 2D SWE, as well as liver biopsy, from September 2020 to June 2022 was conducted in 12 tertiary hospitals in China.
View Article and Find Full Text PDFBackground: Accumulating evidence suggests that metabolic disorders, including type 2 diabetes mellitus (T2DM), can be treated with traditional Chinese medicine formulas, such as the Gegen Qinlian decoction (GQD). This study elucidates the mechanisms by which gut microbes mediate the anti-diabetic effects of GQD.
Methods: We conducted a double-blind randomized clinical trial involving 120 untreated participants with T2DM.
Ion channel drugs have been increasing used for chronic pain management with progress in the development of selective calcium channel modulators. Although ion channel drugs have been proven safe and effective in clinical practice, uncertainty remains regarding its use to treat chronic pain. To standardize the clinical practice of ion channel drug for the treatment of chronic pain, the National Health Commission Capacity Building and Continuing Education Center for Pain Diagnosis and Treatment Special Ability Training Project established an expert group to form an expert consensus on the use of ion channel drugs for the treatment of chronic pain after repeated discussions on existing medical evidence combined with the well clinical experience of experts.
View Article and Find Full Text PDFBackground: Our previous study revealed marked differences in tongue images between individuals with gastric cancer and those without gastric cancer. However, the biological mechanism of tongue images as a disease indicator remains unclear. Tongue coating, a major factor in tongue appearance, is the visible layer on the tongue dorsum that provides a vital environment for oral microorganisms.
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