Highly scalable prefusion-stabilized RSV F vaccine with enhanced immunogenicity and robust protection.

Stabilizing the RSV F protein in its prefusion conformation is crucial for effective vaccine development but has remained a significant challenge. Traditional stabilization methods, such as disulfide bonds and cavity-filling mutations, have been labor-intensive and have often resulted in suboptimal expression levels. Here, we report the design of an RSV prefusion F (preF) antigen using a proline-scanning strategy, incorporating seven proline substitutions to achieve stabilization.

Chlorophyll deficient 5 encodes a DNA helicase and is essential for chloroplast development in rice.

A novel gene CDE5 controlling leaf color was identified. Its causal gene LOC_Os06g45980 was verified by complementation transgenic, expression analysis, RNA sequencing, enzyme activity tests. Leaf color is a critical trait influencing plant biosynthesis, as it directly impacts photosynthesis and dry matter production.

Corrigendum to "Monogenic deficiency in murine intestinal Cdc42 leads to mucosal inflammation that induces crypt dysplasia" [Genes & Dis 11 (2024) 413-429].

[This corrects the article DOI: 10.1016/j.gendis.

Unique and Combined Effects of Small-Group Fraction Vocabulary and Arithmetic Interventions for Students With Mathematical Difficulties.

The purpose of this study was to assess the effects of a fraction vocabulary intervention with fraction arithmetic components on fraction vocabulary knowledge and fraction arithmetic competencies among fourth-grade Chinese students with mathematics difficulties. We randomly assigned 70 students with mathematics difficulties to three conditions: fraction vocabulary only ( = 23), fraction vocabulary with an arithmetic component ( = 23), and a business-as-usual (BaU) condition ( = 24). The students in the fraction vocabulary intervention conditions participated in 10 sessions, occurring three times per week.

Clinical utility of hematological parameters in aplastic anemia.

Hematological parameters available on automated hematology analyzers have been shown to be useful indicators for hematological disorders. However, extensive studies especially in aplastic anemia for these indices are sparse. Our aim was to investigate the clinical utility of hematological parameters in aplastic anemia.

[Targets and mechanisms of neutralizing monoclonal antibodies against Dengue virus].

Dengue fever is a mosquito-borne disease prevalent in tropical and subtropical regions, with its prevalence expanding due to increased global travel. The dengue virus, the causative agent of dengue fever, often co-circulates in the form of four distinct serotypes. Cross-reactive antibodies generated during a primary infection pose a significant risk during secondary infections with different serotypes, and fully protective vaccines and antiviral drugs are yet to be developed.

mRNA vaccines: A promising platform for safer, more effective next-generation Orthopoxvirus immunization.

In recent work, Mucker et al. demonstrated that mRNA-1769 outperforms modified vaccinia Ankara (MVA), which has been deployed against recent mpox virus (MPXV) outbreaks, in reducing clinical symptoms and controlling viral replication, highlighting its potential as a scalable, safe, and effective next-generation platform for orthopoxvirus vaccination.

Innovative nebulization delivery of lipid nanoparticle-encapsulated siRNA: a therapeutic advance for Staphylococcus aureus-induced pneumonia.

Background: Integrin α5β1 plays a crucial role in the invasion of nonphagocytic cells by Staphylococcus aureus (S. aureus), thereby facilitating infection development. Lipid nanoparticles (LNPs) serve as an effective vehicle for delivering small interfering ribonucleic acids (siRNA) that represent a method to knockdown integrin α5β1 in the lungs through nebulization, thereby potentially mitigating the severity of S.

Interaction of the intestinal cytokines-JAKs-STAT3 and 5 axes with RNA N6-methyladenosine to promote chronic inflammation-induced colorectal cancer.

Colorectal cancer (CRC) is one of the most common cancers, with a high mortality rate worldwide. Mounting evidence indicates that mRNA modifications are crucial in RNA metabolism, transcription, processing, splicing, degradation, and translation. Studies show that N6-methyladenosine (m6A) is mammalians' most common epi-transcriptomic modification.

Lemierre's syndrome complicating multiple organ failure caused by Fusobacterium necrophorum subsp. funduliforme F1260: Case report and review.

We described a case of a 24-year-old man with multiple organ failure caused by Fusobacterium necrophorum subsp. funduliforme F1260. This is the first described case of Lemierre's syndrome with multiple organ failure due to F.

Melatonin exerts neuroprotective effects in mice with spinal cord injury by activating the Nrf2/Keap1 signaling pathway via the MT2 receptor.

Spinal cord injury (SCI) is a devastating event that often leads to severe disability, and effective treatments for SCI are currently limited. The present study investigated the potential effects and specific mechanisms of melatonin treatment in SCI. Mice were divided into Sham (Sham), Vehicle (Veh), Melatonin (Mel), and Melatonin + 4-phenyl-2-propionamidotetralin (4P-PDOT) (Mel + 4PP) groups based on randomized allocation.

Integrative analysis of TBI data reveals Lgmn as a key player in immune cell-mediated ferroptosis.

Background: Traumatic brain injury (TBI) is a central nervous system disease caused by external trauma, which has complex pathological and physiological mechanisms. The aim of this study was to explore the correlation between immune cell infiltration and ferroptosis post-TBI.

Methods: This study utilized the GEO database to download TBI data and performed differentially expressed genes (DEGs) and ferroptosis-related differentially expressed genes (FRDEGs) analysis.

Application of machine learning standardized integral area algorithm in measuring the scoliosis.

This study was to develop a computer vision evaluation method to automatically measure the degree of scoliosis based on the machine learning algorithm. For the X-ray images of 204 patients with idiopathic scoliosis who underwent full-spine radiography, histogram equalization of original image was performed before a flipping method was used to magnify asymmetric elements, search for the global maximum pixel value in each line, and scan local maximal pixel value, with the intersection set of two point sets being regarded as candidate anchor points. All fine anchors were fitted with cubic spline algorithm to obtain the approximate curve of the spine, and the degree of scoliosis was measured by the standardized integral area.

Structure and activation mechanism of the rice Salt Overly Sensitive 1 (SOS1) Na/H antiporter.

Salinity is one of the most severe abiotic stresses that adversely affect plant growth and agricultural productivity. The plant Na/H antiporter Salt Overly Sensitive 1 (SOS1) located in the plasma membrane extrudes excess Na out of cells in response to salt stress and confers salt tolerance. However, the molecular mechanism underlying SOS1 activation remains largely elusive.

Monogenic deficiency in murine intestinal Cdc42 leads to mucosal inflammation that induces crypt dysplasia.

CDC42 controls intestinal epithelial (IEC) stem cell (IESC) division. How aberrant CDC42 initiates intestinal inflammation or neoplasia is unclear. We utilized models of inflammatory bowel diseases (IBD), colorectal cancer, aging, and IESC injury to determine the loss of intestinal upon inflammation and neoplasia.

Mpox multi-antigen mRNA vaccine candidates by a simplified manufacturing strategy afford efficient protection against lethal orthopoxvirus challenge.

Current unprecedented mpox outbreaks in non-endemic regions represent a global public health concern. Although two live-attenuated vaccinia virus (VACV)-based vaccines have been urgently approved for people at high risk for mpox, a safer and more effective vaccine that can be available for the general public is desperately needed. By utilizing a simplified manufacturing strategy of mixing DNA plasmids before transcription, we developed two multi-antigen mRNA vaccine candidates, which encode four (M1, A29, B6, A35, termed as Rmix4) or six (M1, H3, A29, E8, B6, A35, termed as Rmix6) mpox virus antigens.

Structure-based neutralizing mechanisms for SARS-CoV-2 antibodies.

The devastating economic and public health consequences caused by the COVID-19 pandemic have prompted outstanding efforts from the scientific community and pharmaceutical companies to develop antibody-based therapeutics against SARS-CoV-2. Those efforts are encouraging and fruitful. An unprecedentedly large number of monoclonal antibodies (mAbs) targeting a large spectrum of epitopes on the spike protein has been developed in the last two years.

Probing Protein-DNA Conformational Dynamics in DNA Damage Recognition: Xeroderma Pigmentosum Group A Stabilizes the Damaged DNA-RPA14 Complex by Controlling Conformational Fluctuation Dynamics.

DNA damage inside biological systems may result in diseases like cancer. One of the major repairing mechanisms is the nucleotide excision repair (NER) that recognizes and repairs the damage caused by several internal and external exposures, such as DNA double-strand distortion due to the chemical modifications. Recognition of lesions is the initial stage of the DNA damage repair, which occurs with the help of several proteins like Replication Protein A (RPA) and Xeroderma Pigmentosum group A (XPA).

A centric view of JAK/STAT5 in intestinal homeostasis, infection, and inflammation.

Cytokines, growth factors or hormones take action through the JAK/STAT5 signaling pathway, which plays a critical role in regulating the intestinal response to infection and inflammation. However, the way in which STAT5 regulates intestinal epithelial compartment is largely ignored due to the lack of genetic tools for proper exploration and because the two STAT5 transcription factors (STAT5A and STAT5B) have some redundant but also distinct functions. In this review article, by focusing on STAT5 functions in the intestinal undifferentiated and differentiated epithelia, we discuss major advances of the growth factor/cytokine-JAK/STAT5 research in view of intestinal mucosal inflammation and immunity.

Structural basis for nucleosome-mediated inhibition of cGAS activity.

Activation of cyclic GMP-AMP synthase (cGAS) through sensing cytosolic double stranded DNA (dsDNA) plays a pivotal role in innate immunity against exogenous infection as well as cellular regulation under stress. Aberrant activation of cGAS induced by self-DNA is related to autoimmune diseases. cGAS accumulates at chromosomes during mitosis or spontaneously in the nucleus.

Mechanistic Insights into the Hydrogen Oxidation Reaction on PtNi Alloys in Alkaline Media: A First-Principles Investigation.

The promising alkaline anion exchange membrane fuel cell suffers from sluggish kinetics of the hydrogen oxidation reaction (HOR). However, the puzzling HOR mechanism hinders the further development of highly active catalysts in alkaline media. In this work, we conducted detailed first-principles calculations to acquire a deep understanding of the alkaline HOR mechanism on PtNi bulk alloys [PtNi(111), PtNi(111), and PtNi(111)] and its surface alloy [PtNi(111)].

Protein O-GlcNAc Modification Links Dietary and Gut Microbial Cues to the Differentiation of Enteroendocrine L Cells.

Intestinal L cells regulate a wide range of metabolic processes, and L-cell dysfunction has been implicated in the pathogenesis of obesity and diabetes. However, it is incompletely understood how luminal signals are integrated to control the development of L cells. Here we show that food availability and gut microbiota-produced short-chain fatty acids control the posttranslational modification on intracellular proteins by O-linked β-N-acetylglucosamine (O-GlcNAc) in intestinal epithelial cells.