Staggered immunization with mRNA vaccines encoding SARS-CoV-2 polymerase or spike antigens broadens the T cell epitope repertoire.

Combining a T cell-targeting mRNA vaccine encoding the conserved SARS-CoV-2 RNA-dependent RNA polymerase, RdRp, with a Spike-encoding mRNA vaccine may offer an additional pathway toward COVID-19 protection. Here, we show that a nucleoside-modified RdRp mRNA vaccine raises robust and durable CD8+ T cell responses in mice. Immunization drives a CD8+ T cell response enriched toward a specific RdRp epitope.

PD-1 blockade plus cisplatin-based chemotherapy in patients with small cell/neuroendocrine bladder and prostate cancers.

Small cell neuroendocrine cancers share biologic similarities across tissue types, including transient response to platinum-based chemotherapy with rapid progression of disease. We report a phase 1b study of pembrolizumab in combination with platinum-based chemotherapy in 15 patients with stage III-IV small cell bladder (cohort 1) or small cell/neuroendocrine prostate cancers (cohort 2). Overall response rate (ORR) is 43% with two-year overall survival (OS) rate of 86% (95% confidence interval [CI]: 0.

CD206 accelerates hepatocellular carcinoma progression by regulating the tumour immune microenvironment and increasing M2-type polarisation of tumour-associated macrophages and inflammation factor expression.

Objective: This study aims to investigate the effect of CD206 on the progression of hepatocellular carcinoma (HCC) and the regulation of the tumour immune microenvironment.

Methods: A subcutaneous mouse model of HCC was established and treated with CD206-overexpressing adenovirus by tail vein injection or CD206 antibody C068C2 by intratumoral injection. The hepatocarcinoma-bearing mice were divided into four groups (IgG+ tail vein adenovirus group, IgG group, C068C2+ tail vein adenovirus group and C068C2 group) to observe the changes in tumour weight and volume with different expression levels of CD206.

Maximizing the Accuracy of Equilibrium Dissociation Constants for Affinity Complexes: From Theory to Practical Recommendations.

The equilibrium dissociation constant () is a major characteristic of affinity complexes and one of the most frequently determined physicochemical parameters. Despite its significance, the values of obtained for the same complex under similar conditions often exhibit considerable discrepancies and sometimes vary by orders of magnitude. These inconsistencies highlight the susceptibility of determination to large systematic errors, even when random errors are small.

Structure and distinct supramolecular organization of a PSII-ACPII dimer from a cryptophyte alga Chroomonas placoidea.

Cryptophyte algae are an evolutionarily distinct and ecologically important group of photosynthetic unicellular eukaryotes. Photosystem II (PSII) of cryptophyte algae associates with alloxanthin chlorophyll a/c-binding proteins (ACPs) to act as the peripheral light-harvesting system, whose supramolecular organization is unknown. Here, we purify the PSII-ACPII supercomplex from a cryptophyte alga Chroomonas placoidea (C.

Mesoporous MOFs with ROS scavenging capacity for the alleviation of inflammation through inhibiting stimulator of interferon genes to promote diabetic wound healing.

Excessive production of reactive oxygen species (ROS) and inflammation are the key problems that impede diabetic wound healing. In particular, dressings with ROS scavenging capacity play a crucial role in the process of chronic wound healing. Herein, Zr-based large-pore mesoporous metal-organic frameworks (mesoMOFs) were successfully developed for the construction of spatially organized cascade bioreactors.

Experimental Study on Liquid Metal Embrittlement of Al-Zn-Mg Aluminum Alloy (7075): From Macromechanical Property Experiment to Microscopic Characterization.

This study is a multiscale experimental investigation into the embrittlement of Al-Zn-Mg aluminum alloy (7075-T6) caused by liquid metal gallium. The results of the experiment demonstrate that the tensile strength of the 7075-T6 aluminum alloy significantly weakens with an increase in the embrittlement temperature and a prolonged embrittlement time, whereas it improves with an increase in the strain rate. On the basis of the analysis of the experimental data, the sensitivity of the embrittlement of 7075-T6 aluminum alloy by liquid gallium to the loading strain rate is significantly higher compared to other environmental factors.

Defining T cell receptor repertoires using nanovial-based binding and functional screening.

The ability to selectively bind to antigenic peptides and secrete effector molecules can define rare and low-affinity populations of cells with therapeutic potential in emerging T cell receptor (TCR) immunotherapies. We leverage cavity-containing hydrogel microparticles, called nanovials, each coated with peptide-major histocompatibility complex (pMHC) monomers to isolate antigen-reactive T cells. T cells are captured and activated by pMHCs inducing the secretion of effector molecules including IFN-γ and granzyme B that are accumulated on nanovials, allowing sorting based on both binding and function.

Structures and organizations of PSI-AcpPCI supercomplexes from red tidal and coral symbiotic photosynthetic dinoflagellates.

Marine photosynthetic dinoflagellates are a group of successful phytoplankton that can form red tides in the ocean and also symbiosis with corals. These features are closely related to the photosynthetic properties of dinoflagellates. We report here three structures of photosystem I (PSI)-chlorophylls (Chls) /-peridinin protein complex (PSI-AcpPCI) from two species of dinoflagellates by single-particle cryoelectron microscopy.

Assessing national vector control micro-planning in Zambia using the 2021 malaria indicator survey.

Background: In 2020, the Zambia National Malaria Elimination Centre targeted the distribution of long-lasting insecticidal nets (LLINs) and indoor-residual spraying (IRS) campaigns based on sub-district micro-planning, where specified geographical areas at the health facility catchment level were assigned to receive either LLINs or IRS. Using data from the 2021 Malaria Indicator Survey (MIS), the objectives of this analysis were to (1) assess how well the micro-planning was followed in distributing LLINs and IRS, (2) investigate factors that contributed to whether households received what was planned, and (3) investigate how overall coverage observed in the 2021 MIS compared to the 2018 MIS conducted prior to micro-planning.

Methods: Households' receipt of ≥ 1 LLIN, and/or IRS within the past 12 months in the 2021 MIS, was compared against the micro-planning area under which the households fell.

Temporal evolution reveals bifurcated lineages in aggressive neuroendocrine small cell prostate cancer trans-differentiation.

Trans-differentiation from an adenocarcinoma to a small cell neuroendocrine state is associated with therapy resistance in multiple cancer types. To gain insight into the underlying molecular events of the trans-differentiation, we perform a multi-omics time course analysis of a pan-small cell neuroendocrine cancer model (termed PARCB), a forward genetic transformation using human prostate basal cells and identify a shared developmental, arc-like, and entropy-high trajectory among all transformation model replicates. Further mapping with single cell resolution reveals two distinct lineages defined by mutually exclusive expression of ASCL1 or ASCL2.

Dual-inhibitory domain iCARs improve the efficiency of the AND-NOT gate CAR T strategy.

CAR (chimeric antigen receptor) T cell therapy has shown clinical success in treating hematological malignancies, but its treatment of solid tumors has been limited. One major challenge is on-target, off-tumor toxicity, where CAR T cells also damage normal tissues that express the targeted antigen. To reduce this detrimental side-effect, Boolean-logic gates like AND-NOT gates have utilized an inhibitory CAR (iCAR) to specifically curb CAR T cell activity at selected nonmalignant tissue sites.

Temperature and emissivity measurement algorithm using a moving emissivity retardation spectral window method based on Lagrange mean value theorem.

The multi-spectral radiation method is a non-contact technique that can measure the temperature and emissivity of an object. However, its core problem lies in solving the underdetermined equation system. Existing numerical emissivity methods require prior knowledge of emissivity, while emissivity function methods need accurate initial conditions.

Macrophage-Associated Genes for Predicting Prognosis and the Tumor Microenvironment in Patients with Hepatocellular Carcinoma.

Background: Hepatocellular carcinoma (HCC) is a highly malignant tumor, which is difficult to treat and has a poor prognosis. Immunotherapy has been a hot topic in liver cancer treatment in recent years, and macrophages play an important role in liver cancer immunotherapy. In this paper, we will use bioinformatics to analyze the significance of macrophage-associated genes (Mags) in hepatocellular carcinoma.

Silk fibroin-gelatin photo-crosslinked 3D-bioprinted hydrogel with MOF-methylene blue nanoparticles for infected wound healing.

Photo-crosslinked hydrogel (PH) is an outstanding candidate for three-dimensional (3D) printing as a wound dressing because of its high efficiency in crosslinking and injectability. In this study, methylene blue (MB)-loaded UiO-66(Ce) nanoparticles (NPs) were synthesized to prevent drug self-aggregation and achieve the photodynamic therapy (PDT) effect for efficient antibacterial action. Then, a composite photocrosslinked silk fibroin (SF)/gelatin hydrogel loaded with MB@UiO-66(Ce) NPs (MB@UiO-66(Ce)/PH) was fabricated.

An Aerial-Wall Robotic Insect That Can Land, Climb, and Take Off from Vertical Surfaces.

Insects that can perform flapping-wing flight, climb on a wall, and switch smoothly between the 2 locomotion regimes provide us with excellent biomimetic models. However, very few biomimetic robots can perform complex locomotion tasks that combine the 2 abilities of climbing and flying. Here, we describe an aerial-wall amphibious robot that is self-contained for flying and climbing, and that can seamlessly move between the air and wall.

IFNγ Transcribed by IRF1 in CD4+ Effector Memory T Cells Promotes Senescence-Associated Pulmonary Fibrosis.

Physiologically aged lungs are prone to senescence-associated pulmonary diseases (SAPD). This study aimed to determine the mechanism and subtype of aged T cells affecting alveolar type II epithelial (AT2) cells, which promote the pathogenesis of senescence-associated pulmonary fibrosis (SAPF). Cell proportions, the relationship between SAPD and T cells, and the aging- and senescence-associated secretory phenotype (SASP) of T cells between young and aged mice were analyzed using lung single-cell transcriptomics.

IRIS: Discovery of cancer immunotherapy targets arising from pre-mRNA alternative splicing.

Alternative splicing (AS) is prevalent in cancer, generating an extensive but largely unexplored repertoire of novel immunotherapy targets. We describe soform peptides from NA splicing for mmunotherapy target creening (IRIS), a computational platform capable of discovering AS-derived tumor antigens (TAs) for T cell receptor (TCR) and chimeric antigen receptor T cell (CAR-T) therapies. IRIS leverages large-scale tumor and normal transcriptome data and incorporates multiple screening approaches to discover AS-derived TAs with tumor-associated or tumor-specific expression.

Hyaluronic acid--lipoic acid granular gel for promoting diabetic wound healing.

Diabetic patients are prone to developing chronic inflammation after trauma and have persistent nonhealing wounds. Reactive oxygen species (ROS) and recurrent bacterial infections at the site of long-term wounds also further delay skin wound healing and tissue regeneration. In this study, a granular gel (which exhibits ROS scavenging and antibacterial properties) is fabricated based on hyaluronic acid--lipoic acid (HA-LA).

Inter-synergized neuroprotection of costunolide engineered bone marrow mesenchymal stem cells targeting system.

Treatment of stroke remains difficult due to the unsatisfactory or unlocalized delivery of small molecule- and cell-based therapeutics in injured brain tissues. This is particularly the case for costunolide (Cos), which is highly neuroprotective and anti-inflammatory but finds great difficulty in reaching the brain. Here, we present that Cos induces the differentiation of bone marrow mesenchymal stem cells (bMSCs) into glia-like cells (C-bMSCs) capable of secreting neurotrophic factors and homing to injured brain tissues.

Cytogeography of Naturalized Populations in Europe.

Autopolyploidization has driven the successful invasion of in East Asia. However, it was believed that only diploid invaded Europe, whereas polyploids never did. Here, molecular identification, ploidy level, and morphological traits of ten populations collected in Europe were compared with previously identified populations from other continents and populations.