Deciphering a reliable synergistic bispecific strategy of rescuing antibodies for SARS-CoV-2 escape variants, including BA.2.86, EG.5.1, and JN.1.

The game between therapeutic monoclonal antibodies (mAbs) and continuously emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has favored the virus, as most therapeutic mAbs have been evaded. Addressing this challenge, we systematically explored a reproducible bispecific antibody (bsAb)-dependent synergistic effect in this study. It could effectively restore the neutralizing activity of the bsAb when any of its single mAbs is escaped by variants. This synergy is primarily attributed to the binding angle of receptor-binding domain (RBD)-5, facilitating inter-spike cross-linking and promoting cryptic epitope exposure that classical antibody cocktails cannot achieve. Furthermore, RBD-5 with RBD-2, RBD-6, and RBD-7, alongside RBD-8, also exhibit significantly enhanced effects. This study not only shifts the paradigm in understanding antibody interactions but paves the way for developing more effective therapeutic antibodies against rapidly mutating SARS-CoV-2, with Dia-19 already showing promise against emerging variants like BA.2.86, EG.5.1, and JN.1.

Coxsackievirus A10 impairs nail regeneration and induces onychomadesis by mimicking DKK1 to attenuate Wnt signaling.

Coxsackievirus A10 (CV-A10) infection, a prominent cause of childhood hand-foot-and-mouth disease (HFMD), frequently manifests with the intriguing phenomenon of onychomadesis, characterized by nail shedding. However, the underlying mechanism is elusive. Here, we found that CV-A10 infection in mice could suppress Wnt/ß-catenin signaling by restraining LDL receptor-related protein 6 (LRP6) phosphorylation and ß-catenin accumulation and lead to onychomadesis. Mechanistically, CV-A10 mimics Dickkopf-related protein 1 (DKK1) to interact with Kringle-containing transmembrane protein 1 (KRM1), the CV-A10 cellular receptor. We further found that Wnt agonist (GSK3ß inhibitor) CHIR99021 can restore nail stem cell differentiation and protect against nail shedding. These findings provide novel insights into the pathogenesis of CV-A10 and related viruses in onychomadesis and guide prognosis assessment and clinical treatment of the disease.

Defining a de novo non-RBM antibody as RBD-8 and its synergistic rescue of immune-evaded antibodies to neutralize Omicron SARS-CoV-2.

Currently, monoclonal antibodies (MAbs) targeting the SARS-CoV-2 receptor binding domain (RBD) of spike (S) protein are classified into seven classes based on their binding epitopes. However, most of these antibodies are seriously impaired by SARS-CoV-2 Omicron and its subvariants, especially the recent BQ.1.1, XBB and its derivatives. Identification of broadly neutralizing MAbs against currently circulating variants is imperative. In this study, we identified a "breathing" cryptic epitope in the S protein, named as RBD-8. Two human MAbs, BIOLS56 and IMCAS74, were isolated recognizing this epitope with broad neutralization abilities against tested sarbecoviruses, including SARS-CoV, pangolin-origin coronaviruses, and all the SARS-CoV-2 variants tested (Omicron BA.4/BA.5, BQ.1.1, and XBB subvariants). Searching through the literature, some more RBD-8 MAbs were defined. More importantly, BIOLS56 rescues the immune-evaded antibody, RBD-5 MAb IMCAS-L4.65, by making a bispecific MAb, to neutralize BQ.1 and BQ.1.1, thereby producing an MAb to cover all the currently circulating Omicron subvariants. Structural analysis reveals that the neutralization effect of RBD-8 antibodies depends on the extent of epitope exposure, which is affected by the angle of antibody binding and the number of up-RBDs induced by angiotensin-converting enzyme 2 binding. This cryptic epitope which recognizes non- receptor binding motif (non-RBM) provides guidance for the development of universal therapeutic antibodies and vaccines against COVID-19.

A nationwide investigation of perchlorate levels in staple foods from China: Implications for human exposure and risk assessment.

Perchlorate is an emerging pollutant and thyroid toxicant frequently occurred in air, water, soil and various foodstuffs. Rice and wheat flour are the most common staple foods, which could accumulate perchlorate from contaminated soils and irrigation water. However, human exposure to perchlorate via rice and wheat flour consumption has only been investigated to a limited extent. Therefore, we collected 207 rice samples and 189 wheat flour samples from 19 provinces in China to assess the level of perchlorate. The levels of perchlorate in rice and wheat flour ranged from not detected (N.D.) to 28.7 ng/g and less than limits of quantification (

The involvement of miR-6615-5p/Smad7 axis and immune imbalance in ammonia-caused inflammatory injury via NF-κB pathway in broiler kidneys.

Ammonia (NH3), a toxic gas, has deleterious effects on chicken health in intensive poultry houses. MicroRNA can mediate inflammation. The complex molecular mechanisms underlying NH3 inhalation-caused inflammation in animal kidneys are still unknown. To explore the mechanisms, a broiler model of NH3 exposure was established. Kidney samples were collected on day 14, 28, and 42, and meat yield was evaluated on day 42. We performed histopathological examination, detected miR-6615-5p and mothers against decapentaplegic homolog 7 (Smad7), and determined inflammatory factors and cytokines in kidneys. The results showed that excess NH3 reduced breast weight and thigh weight, which indicated that excess NH3 impaired meat yield of broilers. Besides, kidney tissues displayed histopathological changes after NH3 exposure. Meanwhile, the increases of inducible nitric oxide synthase (iNOS) activity and nitric oxide content were obtained. The mRNA and protein expression of inflammatory factors, including nuclear factor-κB (NF-κB), cyclooxygenase-2, prostaglandin E synthases, and iNOS increased, indicating that NF-κB pathway was activated. T-helper (Th) 1 and regulatory T (Treg) cytokines were downregulated, whereas Th2 and Th17 cytokines were upregulated, suggesting the occurrence of Th1/Th2 and Treg/Th17 imbalances. In addition, we found that Smad7 was a target gene of miR-6615-5p in chickens. After NH3 exposure, miR-6615-5p expression was elevated, and Smad7 mRNA and protein expression were reduced. In summary, our results suggest that NH3 exposure negatively affected meat yield; and miR-6615/Smad7 axis and immune imbalance participated in NH3-induced inflammatory injury via the NF-κB pathway in broiler kidneys. This study is helpful to understand the mechanism of NH3-induced kidney injury and is meaningful to poultry health and breed aquatics.

Whole transcriptome-based miRNA-mRNA network analysis revealed the mechanism of inflammation-immunosuppressive damage caused by cadmium in common carp spleens.

Cadmium (Cd) is a well-known environmental pollutant and can damage fish. MicroRNAs (miRNAs) can involve in inflammation and immunosuppression. However, the mechanisms of miRNAs are still unclear in common carp (Cyprinus carpio L.) treated by Cd. In current study, 54 juvenile common carp were randomly divided into the control group and the Cd group (0.26 mg L-1 Cd) and were cultured for 30 days. The results revealed inflammatory damage in the spleens of common carp after Cd exposure using morphological construction. There were 23 differentially expressed miRNAs including 17 up-regulated differentially expressed miRNAs (miR-1-4-3p, miR-7-1-5p, miR-7-2-5p, miR-10-43-5p, miR-34-3-5p, miR-128-4-3p, miR-128-5-3p, miR-132-2-5p, miR-132-6-5p, miR-216-3-5p, miR-216-4-5p, miR-375-2-3p, miR-375-4-3p, miR-375-5-3p, miR-375-7-3p, miR-375-8-3p, and miR-724-5p) and 6 down-regulated differentially expressed miRNAs (miR-9-6-5p, miR-25-9-3p, miR-31-3-5p, miR-31-12-5p, miR-103-5-5p, and miR-122-1-3p). The 23 miRNAs regulated 2022 target mRNAs. There were 10 pathways and 9 annotation clusters on 2022 target mRNAs using KEGG and GO analysis, respectively. Among them, 5 pathways (NF-κB signaling pathway, Jak-STAT signaling pathway, MAPK signaling pathway, Th1 and Th2 cell differentiation, and Toll-like receptor signaling pathway) and 7 GO terms (negative regulation of immune system process, T cell mediated immunity, regulation of immune response, inflammatory response, positive regulation of inflammatory response, regulation of inflammatory response, and inflammasome complex) were associated with inflammatory response and immunosuppression. miR-375-4-3p, NF-κB, COX-2, PTGES, and IL-4/13A increased and miR-31-12-5p, miR-9-6-5p, MMP9, IL-11, SPI1, and T-Bet decreased using transcriptome sequencing and RT-qPCR in Cd-treated common carp spleens, which revealed that our results were reliable. Our data indicated that miRNAs mediated inflammation-immunosuppressive injury caused by Cd in common carp spleens using whole transcriptome-based miRNA-mRNA network analysis. Our study provided new insights into the toxicology of Cd exposure.

Efficient and Stable Thin-Film Luminescent Solar Concentrators Enabled by Near-Infrared Emission Perovskite Nanocrystals.

A novel triphenylphosphine (TPP) treatment strategy was developed to prepare the near-infrared emission CsPbI3 nanocrystal (NC)-polymer composite thin-film luminescent solar concentrators (LSCs) featuring high absolute photoluminescence quantum yield (PLQY), low reabsorption, and high stability. The PL emission of the LSCs is centered at about 700 nm with 99.4±0.4 % PLQY and narrow full width at half maximum (FWHM) of 75 meV (30 nm). Compared with LSCs prepared with classic CsPbI3 NCs, the stability of the LSCs after TPP treatments has been greatly improved, even after long-term (30 days) immersion in water and strong mercury-lamp irradiation (50 mW cm-2 ). Owing to the presence of lone-pair electrons on the phosphorus atom, TPP is also used as a photoinitiator, with higher efficiency than other common photoinitiators. Large-area (ca. 75 cm2 ) infrared LSCs were achieved with a high optical conversion efficiency of 3.1 % at a geometric factor of 10.

Direct Hot-Injection Synthesis of Lead Halide Perovskite Nanocubes in Acrylic Monomers for Ultrastable and Bright Nanocrystal-Polymer Composite Films.

In recent years, lead halide perovskite nanocrystals (NCs) have attracted significant attention in both fundamental research and commercial applications because of their excellent optical and optoelectrical properties. However, the protective ligands on the surface of the perovskite NCs could be easily removed after the tedious process of centrifugation, separation, and dispersion, which greatly hampers their stability against light, heat, moisture, and oxygen and limits their practical applications. Here, we report a new post-processing free strategy (i.e., without centrifugation, separation, and dispersion process) of using an ultraviolet (UV)-polymerizable acrylic monomer of lauryl methacrylate as the solvent to synthesize CsPbBr3 NCs, and then adding polyester polyurethane acrylate oligomer, monomer (IBOA), and initiator for direct UV polymerization to fabricate NC-polymer composite films. These films exhibited an improved photoluminescence quantum yield (85-90%) than classic NC films (40-50%), which were processed using octadecene (ODE) as the solvent for NC synthesis and postprocessed for UV polymerization. Significantly, the as-fabricated films by post-processing free strategy exhibited excellent photostability against strong Xe lamp illumination; while the other films using classic methods were quickly photodegraded. Meanwhile, these NC-polymer composite films showed good stability against moisture and heating when aging in water at 50 °C for over 200 h. These films, along with K2SiF6:Mn4+ (KSF) phosphor emitters, were used as downconverters for blue light-emitting diodes in liquid-crystal displays with a wide color gamut of 115% in the International Commission on Illumination (CIE) 1931 color space. This work provides a facile and effective strategy for the preparation of ultrastable and bright color-conversion NC films for the development of the next-generation wide color gamut displays.

Visible light mediated fast iterative RAFT synthesis of amino-based reactive copolymers in water at 20 °C.

The attempts to mediate iterative RAFT polymerization of ionic monomers through visible light irradiation in water at 20 °C is reported, in which complete conversions are attained in several tens of minutes and the propagation suspends/restarts immediately for multiple times on cycling irradiation. This technique suits the one-pot synthesis of NH2 /imidazole-based polymers with tuned structures from homo to random, block, random-block, and block-random-block, thus is robust and promising to control the sequence of the ionized water-soluble reactive copolymers.