Clonal landscape of autoantibody-secreting plasmablasts in COVID-19 patients.

Whereas severe COVID-19 is often associated with elevated autoantibody titers, the underlying mechanism behind their generation has remained unclear. Here we report clonal composition and diversity of autoantibodies in humoral response to SARS-CoV-2. Immunoglobulin repertoire analysis and characterization of plasmablast-derived monoclonal antibodies uncovered clonal expansion of plasmablasts producing cardiolipin (CL)-reactive autoantibodies.

Robust detection of infectious disease, autoimmunity, and cancer from the paratope networks of adaptive immune receptors.

Liquid biopsies based on peripheral blood offer a minimally invasive alternative to solid tissue biopsies for the detection of diseases, primarily cancers. However, such tests currently consider only the serum component of blood, overlooking a potentially rich source of biomarkers: adaptive immune receptors (AIRs) expressed on circulating B and T cells. Machine learning-based classifiers trained on AIRs have been reported to accurately identify not only cancers but also autoimmune and infectious diseases as well.

Protein O-fucosyltransferase 1 promotes PD-L1 stability to drive immune evasion and directs liver cancer to immunotherapy.

Background And Aims: The immunosuppressive tumor microenvironment (TME) plays an essential role in cancer progression and immunotherapy response. Despite the considerable advancements in cancer immunotherapy, the limited response to immune checkpoint blockade (ICB) therapies in patients with hepatocellular carcinoma (HCC) remains a major challenge for its clinical implications. Here, we investigated the molecular basis of the protein O-fucosyltransferase 1 (POFUT1) that drives HCC immune evasion and explored a potential therapeutic strategy for enhancing ICB efficacy.

Evaluation of perceptual interactions between key aldehydes in Kung Pao Chicken.

Aldehydes are the strongest and most abundant aromatic compounds in Kung Pao Chicken. However, the perceptual interactions between these aldehydes are not fully understood. Therefore, the flavor contribution of nine key aldehydes was estimated by determining thresholds.

Endothelium-Derived Engineered Extracellular Vesicles Protect the Pulmonary Endothelial Barrier in Acute Lung Injury.

Acute lung injury (ALI) is a severe respiratory disease with a high mortality rate. The integrity of the pulmonary endothelial barrier influences the development and prognosis of ALI. Therefore, it has become an important target for ALI treatment.

KDM6A promotes hepatocellular carcinoma progression and dictates lenvatinib efficacy by upregulating FGFR4 expression.

Background: Hepatocellular carcinoma (HCC) is one of the major causes of death from cancer and has a very poor prognosis with few effective therapeutic options. Despite the approval of lenvatinib for the treatment of patients suffering from advanced HCC, only a small number of patients can benefit from this targeted therapy.

Methods: Diethylnitrosamine (DEN)-CCL4 mouse liver tumour and the xenograft tumour models were used to evaluate the function of KDM6A in HCC progression.

In Vitro Affinity Maturation of Nanobodies against Mpox Virus A29 Protein Based on Computer-Aided Design.

Mpox virus (MPXV), the most pathogenic zoonotic orthopoxvirus, caused worldwide concern during the SARS-CoV-2 epidemic. Growing evidence suggests that the MPXV surface protein A29 could be a specific diagnostic marker for immunological detection. In this study, a fully synthetic phage display library was screened, revealing two nanobodies (A1 and H8) that specifically recognize A29.

Histone methyltransferase KMT5C drives liver cancer progression and directs therapeutic response to PARP inhibitors.

Background And Aims: Epigenetic plasticity is a major challenge in cancer-targeted therapy. However, the molecular basis governing this process has not yet been clearly defined. Despite the considerable success of poly(ADP-ribose) polymerase inhibitors (PARPi) in cancer therapy, the limited response to PARPi, especially in HCC, has been a bottleneck in its clinical implications.

High performance of visible-light driven hydrogen production over graphdiyne (g-CH)/MOF S-scheme heterojunction.

Among carbon allotropes, 2D graphdiyne (GDY) possesses the merits of good ductility, strong conductivity and an adjustable energy band structure. In this study, a GDY/ZnCo-ZIF S-scheme heterojunction photocatalyst has been successfully prepared by a low-temperature mixing method. Using eosin as a photosensitizer and triethanolamine as a solvent, the hydrogen production of the GDY/ZnCo-ZIF-0.

FAP-targeted CAR-T suppresses MDSCs recruitment to improve the antitumor efficacy of claudin18.2-targeted CAR-T against pancreatic cancer.

Purpose: The claudin 18.2 (CLDN18.2) antigen is frequently expressed in malignant tumors, including pancreatic ductal adenocarcinoma (PDAC).

Screening of phosphorus solubilizing microorganisms in cold environment and their effects on the growth of .

To screen out phosphorus solubilizing strains that can adapt to cold climate in Qinghai Province, , , , , , and were screened with solid plate medium as the primary and liquid medium as the secondary screening, with calcium phosphate, lecithin, and phytic acid as the single source of phosphorus. By comprehensively comparing the size of phosphate solubilizing circle in the solid plate medium and the soluble phosphorus content in the liquid medium, three strains of phosphate solubilizing bacteria with good phosphate solubilizing effects were screened, , , and . The three phosphate solubilizing bacteria were made into liquid ino-culants, and the small rapeseed pot experiment was carried out with two soils with different fertilities in a cold climate in September.

AbAdapt: an adaptive approach to predicting antibody-antigen complex structures from sequence.

Motivation: The scoring of antibody-antigen docked poses starting from unbound homology models has not been systematically optimized for a large and diverse set of input sequences.

Results: To address this need, we have developed AbAdapt, a webserver that accepts antibody and antigen sequences, models their 3D structures, predicts epitope and paratope, and then docks the modeled structures using two established docking engines (Piper and Hex). Each of the key steps has been optimized by developing and training new machine-learning models.

The evolution of structural genomics.

Structural genomics began as a global effort in the 1990s to determine the tertiary structures of all protein families as a response to large-scale genome sequencing projects. The immediate outcome was an influx of tens of thousands of protein structures, many of which had unknown functions. At the time, the value of structural genomics was controversial.

Landscape of infection enhancing antibodies in COVID-19 and healthy donors.

To assess the frequency of SARS-CoV-2 infection in the general population, we searched over 64 million heavy chain antibody sequences from healthy unvaccinated, healthy BNT162b2 vaccinated and COVID-19 patient repertoires for sequences similar to 11 previously reported enhancing antibodies. Although the distribution of sequence identities was similar in all three groups of repertoires, the COVID-19 and healthy vaccinated hits were significantly more clonally expanded than healthy unvaccinated hits. Furthermore, among the tested hits, 17 out of 94 from COVID-19 and 9 out of 59 from healthy vaccinated, compared with only 2 out of 96 from healthy unvaccinated, bound to the enhancing epitope.

Humidity response in Drosophila olfactory sensory neurons requires the mechanosensitive channel TMEM63.

Birds, reptiles and insects have the ability to discriminate humidity levels that influence their survival and geographic distribution. Insects are particularly susceptible to humidity changes due to high surface area to volume ratios, but it remains unclear how humidity sensors transduce humidity signals. Here we identified Or42b-expressing olfactory sensory neurons, which are required for moisture attraction in Drosophila.

Potential of biochar integrated manganese sulfate for promoting pig manure compost humification and its biological mechanism.

This study aimed to clarify the effect of the integrated addition of different proportions of biochar (0 and 5%) and MnSO (0, 0.25%, and 0.50%) to pig manure compost.

An engineered ACE2 decoy neutralizes the SARS-CoV-2 Omicron variant and confers protection against infection in vivo.

The Omicron (B.1.1.

Dual signal-based electrochemical aptasensor for simultaneous detection of Lead(II) and Mercury(II) in environmental water samples.

The Pb-binding aptamer (PBA) and Hg-binding aptamer (HBA) have been widely adopted as biosensing elements for lead(II) (Pb) and mercury (II) (Hg), due to the formation of stable and specific Pb-G-quadruplex and T-Hg-T structures. However, the currently developed electrochemical sensors are only applicable for single-element analysis of Pb or Hg. Herein, a dual signal interface was realized by in-situ grafting the signal tags (Melamine-Cu complex and Nile blue) bearing different redox potentials on the terminal of PBA and HBA that were co-immobilized on gold electrode.

Cyclin J-CDK complexes limit innate immune responses by reducing proinflammatory changes in macrophage metabolism.

Toll-like receptor (TLR) stimulation induces glycolysis and the production of mitochondrial reactive oxygen species (ROS), both of which are critical for inflammatory responses in macrophages. Here, we demonstrated that cyclin J, a TLR-inducible member of the cyclin family, reduced cytokine production in macrophages by coordinately controlling glycolysis and mitochondrial functions. Cyclin J interacted with cyclin-dependent kinases (CDKs), which increased the phosphorylation of a subset of CDK substrates, including the transcription factor FoxK1 and the GTPase Drp1.

Solid digestate biochar amendment on pig manure composting: Nitrogen cycle and balance.

Effect of solid digestate biochar (DB) on nitrogen cycle and balance was evaluated during composting by adding DB into mixtures of pig manure and Lycium chinensis branch filings. Results indicated that DB addition improved composting microenvironment and increased the total N content of the final product. Furthermore, N balance calculation indicated that the NH and NO emissions accounted for 72.

Mechanotransduction Ion Channels in Hearing and Touch.

The ability of living organisms to detect mechanical force originates from mechanotransduction ion channels, which convert membrane tension into electrical or chemical signals that are transmitted to the brain. A variety of studies on touch and sound perception in both vertebrates and invertebrates have broadened our understanding of mechanotransduction and identified promising candidates for mechanotransduction ion channels. Here, we discussed the physiological properties of mechanotransduction ion channels in hearing and touch, the identification of their molecular entities, and recent structural studies providing insights to their gating mechanisms in force sensing.

Recovery of phosphate from aqueous solution by dewatered dry sludge biochar and its feasibility in fertilizer use.

Discharging of dewatered dry sludge into the environment can trigger irreversible environmental damage. The treatment of dewatered dry sludge into a valuable biochar product is essential for the sustainability of resources and environmental safety. In this study, we examined the removal of phosphate from water bodies by adsorption of biochar that had been prepared from dewatered dry sludge with different pyrolysis temperatures.