An erythroid-specific lentiviral vector improves anemia and iron metabolism in a new model of XLSA.

X-linked sideroblastic anemia (XLSA) is a congenital anemia caused by mutations in ALAS2, a gene responsible for heme synthesis. Treatments are limited to pyridoxine supplements and blood transfusions, offering no definitive cure except for allogeneic hematopoietic stem cell transplantation, only accessible to a subset of patients. The absence of a suitable animal model has hindered the development of gene therapy research for this disease.

Efficacy and safety of Dachaihu decoction for sepsis: A randomized controlled trial.

Background: Sepsis is a critical condition characterized by multi-organ dysfunction (MODS) that presents significant treatment challenges. Traditional Chinese medicine (TCM), particularly Dachaihu decoction (DCH), has shown potential in addressing sepsis-related complications.

Purpose: To comprehensively evaluate the efficacy and safety of DCH in the treatment of sepsis.

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.

Improved influenza vaccine responses after expression of multiple viral glycoproteins from a single mRNA.

Influenza viruses cause substantial morbidity and mortality every year despite seasonal vaccination. mRNA-based vaccines have the potential to elicit more protective immune responses, but for maximal breadth and durability, it is desirable to deliver both the viral hemagglutinin and neuraminidase glycoproteins. Delivering multiple antigens individually, however, complicates manufacturing and increases cost, thus it would be beneficial to express both proteins from a single mRNA.

BoReMi: Bokeh-based jupyter-interface for registering spatio-molecular data to related microscopy images.

Spatio-molecular data and microscopy images provide complementary information, essential to study structure and function of spatially organised multicellular systems such as healthy or diseased tissues. However, aligning these two types of data can be challenging due to distortions and differences in resolution, orientation, and position. Manual registration is tedious but may be necessary for challenging samples as well as for the generation of ground-truth data sets that enable benchmarking of existing and emerging automated alignment tools.

Bivalent norovirus mRNA vaccine elicits cellular and humoral responses protecting human enteroids from GII.4 infection.

Nucleoside-modified mRNA-LNP vaccines have revolutionized vaccine development against infectious pathogens due to their ability to elicit potent humoral and cellular immune responses. In this article, we present the results of the first norovirus vaccine candidate employing mRNA-LNP platform technology. The mRNA-LNP bivalent vaccine encoding the major capsid protein VP1 from GI.

The roles of CD4 T cell help, sex, and dose in the induction of protective CD8 T cells against a lethal poxvirus by mRNA-LNP vaccines.

The role of CD4 T cells in the induction of protective CD8 T cells by mRNA lipid nanoparticle (LNP) vaccines is unknown. We used B6 or mice depleted or not of CD4 T cells and LNP vaccines loaded with mRNAs encoding the ectromelia virus (ECTV) MHC class I H-2 K-restricted immunodominant CD8 T cell epitope TSYKFESV (TSYKFESV mRNA-LNPs) or the ECTV EVM158 protein, which contains TSYKFESV (EVM-158 mRNA-LNPs). Following prime and boost with 10 μg of either vaccine, K-TSYKFESV-specific CD8 T cells fully protected male and female mice from ECTV at 29 (both mRNA-LNPs) or 90 days (EVM158 mRNA-LNPs) post boost (dpb) independently of CD4 T cells.

Non-malarial febrile illness: a systematic review of published aetiological studies and case reports from China, 1980-2015.

Background: Rapid point-of-care tests for malaria are now widely used in many countries to guide the initial clinical management of patients presenting with febrile illness. With China having recently achieved malaria elimination, better understanding regarding the identity and distribution of major non-malarial causes of febrile illnesses is of particular importance to inform evidence-based empirical treatment policy.

Methods: A systematic review of published literature was undertaken to characterise the spectrum of pathogens causing non-malaria febrile illness in China (1980-2015).

Using the Lives Saved Tool to inform global nutrition advocacy.

Background: The global nutrition community has been interested in investigating investment strategies that could be used to promote an increased focus and investment in nutrition programming in low- and middle-income countries.

Methods: The Lives Saved Tool (LiST) was used to evaluate lives saved and the costs of nutrition interventions in nine high-burden countries. In this case study, we detail the analyses that were conducted with LiST and how the results were packaged to develop Nourish the Future - a five-year proposal for the US government to scale up lifesaving malnutrition interventions.

Comparison of the immunogenicity of mRNA-encoded and protein HIV-1 Env-ferritin nanoparticle designs.

Nucleoside-modified mRNA technology has revolutionized vaccine development with the success of mRNA COVID-19 vaccines. We used modified mRNA technology for the design of envelopes (Env) to induce HIV-1 broadly neutralizing antibodies (bnAbs). However, unlike SARS-CoV-2 neutralizing antibodies that are readily made, HIV-1 bnAb induction is disfavored by the immune system because of the rarity of bnAb B cell precursors and the cross-reactivity of bnAbs targeting certain Env epitopes with host molecules, thus requiring optimized immunogen design.

Computationally designed mRNA-launched protein nanoparticle vaccines.

Both 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.

Clinical characteristics and outcome of omphalocele and gastroschisis: a 20-year multicenter regional experience.

Omphalocele and gastroschisis are the most common types of abdominal wall defects. Comprehensive local experience helps parents to make decisions on the pregnancy and foresee the disease journey. A retrospective review of abdominal wall defect patients in all three pediatric surgical centers in Hong Kong between January 2003 and February 2023 was conducted.

Proteomic profiling improves prognostic risk stratification of the Sarculator nomogram in soft tissue sarcomas of the extremities and trunk wall.

Background: High-risk soft tissue sarcomas of the extremities and trunk wall (eSTS), as defined by the Sarculator nomogram, are more likely to benefit from (neo)adjuvant anthracycline-based therapy compared to low/intermediate-risk patients. The biology underpinning these differential treatment outcomes remain unknown.

Methods: We analysed proteomic profiles and clinical outcomes of 123 eSTS patients.

Immature dendritic cell-targeting mRNA vaccine expressing PfCSP enhances protective immune responses against liver infection.

Resurgence in malaria has been noted in 2022 with 249 million clinical cases resulting in 608,000 deaths, mostly in children under five. Two vaccines, RTS, S, and more recently R21, targeting the circumsporozoite protein (CSP) are recommended by the WHO but are not yet widely available. Strong humoral responses to neutralize sporozoites before they can infect the hepatocytes are important for vaccine-mediated protection.

: a pre- and post- genome-wide association studies pipeline for detecting phenotype-associated genome rearrangement events.

The use of -mers to capture genetic variation in bacterial genome-wide association studies (bGWAS) has demonstrated its effectiveness in overcoming the plasticity of bacterial genomes by providing a comprehensive array of genetic variants in a genome set that is not confined to a single reference genome. However, little attempt has been made to interpret -mers in the context of genome rearrangements, partly due to challenges in the exhaustive and high-throughput identification of genome structure and individual rearrangement events. Here, we present , a pre- and post-bGWAS processing methodology that leverages the unique properties of -mers to facilitate bGWAS for genome rearrangements.

Use of HSC-targeted LNP to generate a mouse model of lethal α-thalassemia and treatment via lentiviral gene therapy.

α-Thalassemia (AT) is one of the most commonly occurring inherited hematological diseases. However, few treatments are available, and allogeneic bone marrow transplantation is the only available therapeutic option for patients with severe AT. Research into AT has remained limited because of a lack of adult mouse models, with severe AT typically resulting in in utero lethality.

Transient growth factor expression via mRNA in lipid nanoparticles promotes hepatocyte cell therapy in mice.

Primary human hepatocyte (PHH) transplantation is a promising alternative to liver transplantation, whereby liver function could be restored by partial repopulation of the diseased organ with healthy cells. However, currently PHH engraftment efficiency is low and benefits are not maintained long-term. Here we refine two male mouse models of human chronic and acute liver diseases to recapitulate compromised hepatocyte proliferation observed in nearly all human liver diseases by overexpression of p21 in hepatocytes.

Clinical Implications and Molecular Features of Extracellular Matrix Networks in Soft Tissue Sarcomas.

Purpose: The landscape of extracellular matrix (ECM) alterations in soft tissue sarcomas (STS) remains poorly characterized. We aimed to investigate the tumor ECM and adhesion signaling networks present in STS and their clinical implications.

Experimental Design: Proteomic and clinical data from 321 patients across 11 histological subtypes were analyzed to define ECM and integrin adhesion networks.

Machine-Learning-Assisted Discovery of Mechanosynthesized Lead-Free Metal Halide Perovskites for the Oxidative Photocatalytic Cleavage of Alkenes.

Lead-free metal halide perovskites can potentially be air- and water-stable photocatalysts for organic synthesis, but there are limited studies on them for this application. Separately, machine learning (ML), a critical subfield of artificial intelligence, has played a pivotal role in identifying correlations and formulating predictions based on extensive datasets. Herein, an iterative workflow by incorporating high-throughput experimental data with ML to discover new lead-free metal halide perovskite photocatalysts for the aerobic oxidation of styrene is described.

Distinct components of nucleoside-modified messenger RNA vaccines cooperate to instruct efficient germinal center responses.

Nucleoside-modified mRNA vaccines elicit protective antibodies through their ability to promote T follicular helper (Tfh) cells. The lipid nanoparticle (LNP) component of mRNA vaccines possesses inherent adjuvant activity. However, to what extent the nucleoside-modified mRNA can be sensed and contribute to Tfh cell responses remains largely undefined.

Challenges in reducing maternal and neonatal mortality in Niger: an in-depth case study.

Introduction: Recent modelled estimates suggest that Niger made progress in maternal mortality since 2000. However, neonatal mortality has not declined since 2012 and maternal mortality estimates were based on limited data. We researched the drivers of progress and challenges.