A modular vaccine platform for optimized lipid nanoparticle mRNA immunogenicity.

Certain messenger RNA antigens in mRNA vaccines elicit an insufficient immune response due to challenges in cell surface translocation (CST) of the antigens. Here we develop a modular vaccine platform (MVP) to enhance the immunogenicity of challenging mRNA antigens by optimizing antigen expression and presentation. MVPs enable the modular assembly of chimeric antigens.

What is the influence of centennial evolution from macrophytes to algae on organic matter burial in the upper reaches of Yangtze River from the biomarker carbon isotope fingerprint.

Identification and quantification of sediment organic matter (OM) in the plateau eutrophic lakes, which are strongly influenced by human activities, is noticeable in the study of regional carbon (C) burial and global change. The abundance of n-alkanes and compound-specific carbon isotope (δC) in sediment cores have been widely utilized as proxies. Here, the n-alkane diagnostic pattern, δC end-member model, ecological data, and the historical OM input, associated with the ecosystem evolutionary processes were investigated.

Spatially Resolved Panoramic in vivo CRISPR Screen via Perturb-DBiT.

Spatially resolved in vivo CRISPR screening integrates gene editing with spatial transcriptomics to examine how genetic perturbations alter gene expression within native tissue environments. However, current methods are limited to small perturbation panels and the detection of a narrow subset of protein-coding RNAs. We present Perturb-DBiT, a distinct and versatile approach for the simultaneous co-sequencing of spatial total RNA whole-transcriptome and single-guide RNAs (sgRNAs), base-by-base, on the same tissue section.

The impact of orthopoxvirus vaccination and Mpox infection on cross-protective immunity: a multicohort observational study.

Background: Cross-reactive immune memory responses to orthopoxviruses in humans remain poorly characterised despite their relevance for vaccine design and outbreak control. We aimed to assess the magnitude, specificity, and durability of cross-reactive immune responses elicited by smallpox vaccines and mpox virus infection.

Methods: We did a multicohort observational study involving participants from the USA, Brazil, and Portugal across four groups: Dryvax (first-generation smallpox vaccine) recipients vaccinated 40-80 years ago, JYNNEOS (third-generation smallpox vaccine) recipients vaccinated within the past year, a cohort receiving both vaccines, and patients infected with clade IIb mpox.

Sensitive detection of synthetic response to cancer immunotherapy driven by gene paralog pairs.

Immunotherapies, including checkpoint blockade and chimeric antigen receptor T cell (CAR-T) therapy, have revolutionized cancer treatment; however, many patients remain unresponsive to these treatments or relapse following treatment. CRISPR screenings have been used to identify novel single gene targets that can enhance immunotherapy effectiveness, but the identification of combinational targets remains a challenge. Here, we introduce a computational approach that uses sgRNA set enrichment analysis to identify cancer-intrinsic paralog pairs for enhancing immunotherapy using genome-wide screens.

Cas12a-knock-in mice for multiplexed genome editing, disease modelling and immune-cell engineering.

The pleiotropic effects of human disease and the complex nature of gene-interaction networks require knock-in mice allowing for multiplexed gene perturbations. Here we describe a series of knock-in mice with a C57BL/6 background and with the conditional or constitutive expression of LbCas12a or of high-fidelity enhanced AsCas12a, which were inserted at the Rosa26 locus. The constitutive expression of Cas12a in the mice did not lead to discernible pathology and enabled efficient multiplexed genome engineering.

Institutional Capacity and Practices for Maternal Anemia in China.

In China, a range of anemia prevention and treatment measures have been developed and implemented in recent decades. These measures provide a regulatory basis for implementing standardized maternal anemia prevention and treatment services in China. However, little is known about the adoption of these interventions by health professionals, the capacity of health facilities to screen for iron deficiency and anemia, or the level of compliance among pregnant and lactating women (PLW).

Multiplexed inhibition of immunosuppressive genes with Cas13d for combinatorial cancer immunotherapy.

The complex nature of the immunosuppressive tumor microenvironment (TME) requires multi-agent combinations for optimal immunotherapy. Here we describe multiplex universal combinatorial immunotherapy via gene silencing (MUCIG), which uses CRISPR-Cas13d to silence multiple endogenous immunosuppressive genes in the TME, promoting TME remodeling and enhancing antitumor immunity. MUCIG vectors targeting four genes delivered by adeno-associated virus (AAV) (Cd274/Pdl1, Lgals9/Galectin9, Lgals3/Galectin3 and Cd47; AAV-Cas13d-PGGC) demonstrate significant antitumor efficacy across multiple syngeneic tumor models, remodeling the TME by increasing CD8 T-cell infiltration while reducing neutrophils.

Spatially Resolved CRISPR Screen Sequencing via Perturb-DBiT.

Perturb-seq enabled the profiling of transcriptional effects of genetic perturbations in single cells but lacks the ability to examine the impact on tissue environments. We present Perturb-DBiT for simultaneous co-sequencing of spatial transcriptome and guide RNAs (gRNAs) on the same tissue section for in vivo CRISPR screen with genome-scale gRNA libraries, offering a comprehensive understanding of how genetic modifications affect cellular behavior and tissue architecture. This platform supports a variety of delivery vectors, gRNA library sizes, and tissue preparations, along with two distinct gRNA capture methods, making it adaptable to a wide range of experimental setups.

Quantifying the environmental fate and source of nitrate contamination using dual-isotope tracing coupled with nitrogen cascade model on the basin scale.

Nitrate (NO) contamination in riverine networks has threatened the environment and human health. Clarifying the NO source and environmental fate within the basin under different underlying surfaces is essential for water body protection, especially China's two mother rivers. A series of combination methods were established i.

PTX3 exacerbates hepatocyte pyroptosis in hepatic ischemia-reperfusion injury by promoting macrophage M1 polarization.

Backgrounds: Hepatic ischemia-reperfusion injury (IRI) triggers macrophage activation, which in turn mediates inflammatory responses and affects tissue repair and injury severity. Pentraxin 3 (PTX3) is vital in immune regulation and inflammatory processes. In this study, we aim to investigate the potential role of PTX3 in macrophage-mediated hepatic IRI.

Analysis of the relationship between the quality of antenatal care examinations and the incidence of preterm birth and low birth weight.

Background: Antenatal care (ANC) plays a crucial role in ensuring maternal and child safety and reducing adverse delivery outcomes. This study aimed to analyze the association between the quality of ANC and the occurrence of preterm birth and low birth weight in a sample of the population from 16 regions in 8 provinces in China.

Methods: Data from all closed cases of pregnant women and newborns reported in the Maternal and Child Health Monitoring System from January 1, 2018, to December 31, 2018, in 16 monitoring regions across 8 provinces in China were collected and included in the analysis, resulting in a total of 49,084 pregnant women and 49,026 newborns.

Single-cell CAR T atlas reveals type 2 function in 8-year leukaemia remission.

Despite a high response rate in chimeric antigen receptor (CAR) T cell therapy for acute lymphocytic leukaemia (ALL), approximately 50% of patients relapse within the first year, representing an urgent question to address in the next stage of cellular immunotherapy. Here, to investigate the molecular determinants of ultralong CAR T cell persistence, we obtained a single-cell multi-omics atlas from 695,819 pre-infusion CAR T cells at the basal level or after CAR-specific stimulation from 82 paediatric patients with ALL enrolled in the first two CAR T ALL clinical trials and 6 healthy donors. We identified that elevated type 2 functionality in CAR T infusion products is significantly associated with patients maintaining a median B cell aplasia duration of 8.

Fertility Intentions Among Reproductive-Age Women - Three Provinces, China, 2023.

What Is Already Known About This Topic?: Low fertility rates have become the most important risk affecting the balanced development of the population in China.

What Is Added By This Report?: About 80.0% of childless women had fertility intentions, 31.

In vivo AAV-SB-CRISPR screens of tumor-infiltrating primary NK cells identify genetic checkpoints of CAR-NK therapy.

Natural killer (NK) cells have clinical potential against cancer; however, multiple limitations hinder the success of NK cell therapy. Here, we performed unbiased functional mapping of tumor-infiltrating NK (TINK) cells using in vivo adeno-associated virus (AAV)-SB (Sleeping Beauty)-CRISPR (clustered regularly interspaced short palindromic repeats) screens in four solid tumor mouse models. In parallel, we characterized single-cell transcriptomic landscapes of TINK cells, which identified previously unexplored subpopulations of NK cells and differentially expressed TINK genes.

Immunometabolism of CD8 T cell differentiation in cancer.

CD8 cytotoxic T lymphocytes (CTLs) are central mediators of tumor immunity and immunotherapies. Upon tumor antigen recognition, CTLs differentiate from naive/memory-like toward terminally exhausted populations with more limited function against tumors. Such differentiation is regulated by both immune signals, including T cell receptors (TCRs), co-stimulation, and cytokines, and metabolism-associated processes.

Prevalence and influencing factors of anemia among pregnant women across first, second and third trimesters of pregnancy in monitoring areas, from 2016 to 2020: a population-based multi-center cohort study.

Objective: To assess the prevalence of anemia among pregnant women across their entire pregnancy and the factors affecting it in the monitoring areas.

Methods: A total of 108,351 pregnant women who received antenatal health care and delivered from January 1, 2016 to December 31, 2020 in 15 monitoring counties of 8 provinces in the Maternal and Newborn Health Monitoring Program (MNHMP) of National Center for Women and Children's Health (NCWCH) were selected as the study subjects. The anemia status among the subjects across their first, second and third trimester of pregnancy and the influencing factors were analyzed.

Genome scale CRISPR screens identify actin capping proteins as key modulators of therapeutic responses to radiation and immunotherapy.

Radiotherapy (RT), is a fundamental treatment for malignant tumors and is used in over half of cancer patients. As radiation can promote anti-tumor immune effects, a promising therapeutic strategy is to combine radiation with immune checkpoint inhibitors (ICIs). However, the genetic determinants that impact therapeutic response in the context of combination therapy with radiation and ICI have not been systematically investigated.

Pooled screening with next-generation gene editing tools.

Pooled screening creates a pool of cells with genetic variants, allowing for the simultaneous examination for changes in behavior or function. By selectively inducing mutations or perturbing expression, it enables scientists to systematically investigate the function of genes or genetic elements. Emerging gene editing tools, such as CRISPR, coupled with advances in sequencing and computational capabilities, provide growing opportunities to understand biological processes in humans, animals, and plants as well as to identify potential targets for therapeutic interventions and agricultural research.