Unraveling the genetic mysteries of spinal muscular atrophy in Chinese families.

Objective: Spinal muscular atrophy (SMA) is a motor neuron disorder encompassing 5q and non-5q forms, causing muscle weakness and atrophy due to spinal cord cell degeneration. Understanding its genetic basis is crucial for genetic counseling and personalized treatment options.

Methods: This study retrospectively analyzed families of patients suspected of SMA at our institution from February 2006 to March 2024.

The endonuclease activity of MCPIP1 controls the neoplastic transformation of epithelial cells via the c-Met/CD44 axis.

The RNase activity of MCPIP1 is essential for regulating cellular homeostasis, proliferation, and tumorigenesis. Our study elucidates the effects of downregulation of MCPIP1 expression and an RNase-inactivating mutation (D141N) on normal epithelial kidney cells, indicating that MCPIP1 expression is a key factor that suppresses neoplastic transformation. We observed that either expression downregulation or mutation of MCPIP1 significantly increased its clonogenicity and altered the expression of cancer stem cell (CSC) markers and factors involved in epithelial-to-mesenchymal transition (EMT).

Trichoderma virens XZ11-1 producing siderophores inhibits the infection of Fusarium oxysporum and promotes plant growth in banana plants.

Background: Banana Fusarium wilt caused by Fusarium oxysporum f. sp. cubense is a soil-borne fungal disease.

A ROS-responsive hydrogel encapsulated with matrix metalloproteinase-13 siRNA nanocarriers to attenuate osteoarthritis progression.

RNA interference (RNAi) and oxidative stress inhibition therapeutic strategies have been extensively utilized in the treatment of osteoarthritis (OA), the most prevalent degenerative joint disease. However, the synergistic effects of these approaches on attenuating OA progression remain largely unexplored. In this study, matrix metalloproteinase-13 siRNA (siMMP-13) was incorporated onto polyethylenimine (PEI)-polyethylene glycol (PEG) modified FeO nanoparticles, forming a nucleic acid nanocarrier termed si-Fe NPs.

SIRT2 and ALDH1A1 as critical enzymes for astrocytic GABA production in Alzheimer's disease.

Background: Alzheimer's Disease (AD) is a neurodegenerative disease with drastically altered astrocytic metabolism. Astrocytic GABA and HO are associated with memory impairment in AD and synthesized through the Monoamine Oxidase B (MAOB)-mediated multi-step degradation of putrescine. However, the enzymes downstream to MAOB in this pathway remain unidentified.

A Facile Approach To Develop Ion Pair Micelles Satellited Freshly Derived Neutrophils For Targeted Tumor Therapy.

Immune cells show enormous potential for targeted nanoparticle delivery due to their intrinsic tumor-homing skills. However, the immune cells can internalize the nanoparticles, leading to cellular functional impairments, degradation of the nanoparticles, and delayed release of drugs from the immune cells. To address these issues, this study introduces an approach for the synthesis of freshly derived neutrophils (NUs)-based nanocarriers system where the NUs are surfaced by dialdehyde alginate-coated self-assembled micelles loaded with mitoxantrone (MIT) and indocyanine green (ICG) (i.

Green Synthesis of Red Fluorescent Carbon Quantum Dots: Antioxidant, Hemolytic, Biocompatibility, and Photocatalytic Applications.

A straightforward one-step hydrothermal method is introduced for synthesizing highly efficient red fluorescence carbon dots (R-CQDs), utilizing Heena leaf (Lawsonia inermis) powder as the carbon precursor. The resulting R-CQDs exhibit excitation at 540 nm and emission at 675 nm, a high absolute photoluminescence (PL) with quantum yield of 40% in ethanol. Various physicochemical characterization was employed to confirm successful formation of R-CQDs including UV-Vis Spectroscopy, Fourier Transform Infrared (FT-IR) Spectroscopy, X-ray diffraction Spectroscopy, Transmission Electron Microscopy (TEM) and X-ray Photoelectron Spectroscopy.

Genome-Guided Identification and Characterisation of Broad-Spectrum Antimicrobial Compounds of Bacillus velezensis Strain PD9 Isolated from Stingless Bee Propolis.

The emergence of multidrug-resistant pathogens presents a significant global health challenge, which is primarily fuelled by overuse and misuse of antibiotics. Bacteria-derived antimicrobial metabolites offer a promising alternative strategy for combating antimicrobial resistance issues. Bacillus velezensis PD9 (BvPD9), isolated from stingless bee propolis, has been reported to have antibacterial activities against methicillin-resistant Staphylococcus aureus (MRSA).

Daratumumab plus lenalidomide/dexamethasone in untreated multiple myeloma: analysis of key subgroups of the MAIA study.

In the MAIA study (median follow-up, 56.2 months), daratumumab plus lenalidomide and dexamethasone (D-Rd) significantly improved progression-free survival (PFS) and overall survival versus lenalidomide and dexamethasone (Rd) alone in transplant-ineligible newly diagnosed multiple myeloma (NDMM). In this post hoc analysis of clinically important subgroups in MAIA (median follow-up, 64.

Deep learning reveals diverging effects of altitude on aging.

Aging is influenced by a complex interplay of multifarious factors, including an individual's genetics, environment, and lifestyle. Notably, high altitude may impact aging and age-related diseases through exposures such as hypoxia and ultraviolet (UV) radiation. To investigate this, we mined risk exposure data (summary exposure value), disease burden data (disability-adjusted life years (DALYs)), and death rates and life expectancy from the Global Health Data Exchange (GHDx) and National Data Management Center for Health of Ethiopia for each subnational region of Ethiopia, a country with considerable differences in the living altitude.

Management of post-operative anaemia in patients undergoing surgery for colorectal cancer: a qualitative focus group-based study.

Background: Optimal management of anaemia following surgery for colorectal cancer remains unclear. Peri-operative anaemia is common in patients undergoing resectional surgery for colorectal cancer. A significant amount of research has been conducted into the management of pre-operative anaemia; however, little work has investigated post-operative anaemia.

Molecular regulation and domestication of parthenocarpy in cucumber.

Parthenocarpy is a pivotal trait that enhances the yield and quality of fruit crops by enabling the development of seedless fruits. Here we unveil a molecular framework for the regulation and domestication of parthenocarpy in cucumber (Cucumis sativus L.).

Loss of correlated proteasomal subunit expression selectively promotes the 20S state which underlies luminal breast tumorigenicity.

Why cancer cells disproportionately accumulate polyubiquitinated proteotoxic proteins despite high proteasomal activity is an outstanding question. While mis-regulated ubiquitination is a contributing factor, here we show that a structurally-perturbed and sub-optimally functioning proteasome is at the core of altered proteostasis in tumors. By integrating the gene coexpression signatures of proteasomal subunits in breast cancer (BrCa) patient tissues with the atomistic details of 26S holocomplex, we find that the transcriptional deregulation induced-stoichiometric imbalances perpetuate with disease severity.

IL-33-activated ILC2s induce tertiary lymphoid structures in pancreatic cancer.

Tertiary lymphoid structures (TLSs) are de novo ectopic lymphoid aggregates that regulate immunity in chronically inflamed tissues, including tumours. Although TLSs form due to inflammation-triggered activation of the lymphotoxin (LT)-LTβ receptor (LTβR) pathway, the inflammatory signals and cells that induce TLSs remain incompletely identified. Here we show that interleukin-33 (IL-33), the alarmin released by inflamed tissues, induces TLSs.

Massively parallel characterization of transcriptional regulatory elements.

The human genome contains millions of candidate cis-regulatory elements (cCREs) with cell-type-specific activities that shape both health and many disease states. However, we lack a functional understanding of the sequence features that control the activity and cell-type-specific features of these cCREs. Here we used lentivirus-based massively parallel reporter assays (lentiMPRAs) to test the regulatory activity of more than 680,000 sequences, representing an extensive set of annotated cCREs among three cell types (HepG2, K562 and WTC11), and found that 41.

De novo designed proteins neutralize lethal snake venom toxins.

Snakebite envenoming remains a devastating and neglected tropical disease, claiming over 100,000 lives annually and causing severe complications and long-lasting disabilities for many more. Three-finger toxins (3FTx) are highly toxic components of elapid snake venoms that can cause diverse pathologies, including severe tissue damage and inhibition of nicotinic acetylcholine receptors, resulting in life-threatening neurotoxicity. At present, the only available treatments for snakebites consist of polyclonal antibodies derived from the plasma of immunized animals, which have high cost and limited efficacy against 3FTxs.

Deciphering the safeguarding role of cysteine residues in p53 against HO-induced oxidation using high-resolution native mass spectrometry.

The transcription factor p53 is exquisitely sensitive and selective to a broad variety of cellular environments. Several studies have reported that oxidative stress weakens the p53-DNA binding affinity for certain promoters depending on the oxidation mechanism. Despite this body of work, the precise mechanisms by which the physiologically relevant DNA-p53 tetramer complex senses cellular stresses caused by HO are still unknown.

Mutated IL-32θ (A94V) inhibits COX2, GM-CSF and CYP1A1 through AhR/ARNT and MAPKs/NF-κB/AP-1 in keratinocytes exposed to PM.

Exposure to particulate matter (PM) in the air harms human health. Most studies on particulate matter's (PM) effects have primarily focused on respiratory and cardiovascular diseases. Recently, IL-32θ, one of the IL-32 isoforms, has been demonstrated to modulate cancer development and inflammatory responses.

Draft genome sequence of Kei apple, an underutilized African tree crop.

To address food and nutrition security in the face of burgeoning global populations and erratic climatic conditions there is a need to include nutrient dense, climatic resilient but neglected indigenous fruit trees in agrifood systems. Here we present the draft genome sequence of Kei Apple, Dovyalis afra, a neglected indigenous African fruit tree with untapped potential to contribute to nutrient security and improved livelihoods. Our long-read-based genome assembly comprises 440 Mbp sequence across 1190 contigs with a N50 and L50 of 13.

A preliminary evaluation of a fast, low-cost, and high-throughput nucleic acid extraction method for bacterial microbiota profiling in low-microbial biomass samples.

The respiratory tract is colonized with low-density microbial communities, which have been shown to impact human respiratory health through microbiota-host interactions. However, a lack of fast and cost-effective nucleic acid extraction method for low-microbial biomass samples hinders investigation of respiratory microbiota. Here, we performed a pilot study to assess the suitability of the NAxtra nucleic acid extraction protocol for profiling bacterial microbiota in respiratory samples.

Microglial NLRP3-gasdermin D activation impairs blood-brain barrier integrity through interleukin-1β-independent neutrophil chemotaxis upon peripheral inflammation in mice.

Blood-brain barrier (BBB) disintegration is a key contributor to neuroinflammation; however, the biological processes governing BBB permeability under physiological conditions remain unclear. Here, we investigate the role of NLRP3 inflammasome in BBB disruption following peripheral inflammatory challenges. Repeated intraperitoneal lipopolysaccharide administration causes NLRP3-dependent BBB permeabilization and myeloid cell infiltration into the brain.

Morphological and functional convergence of visual projection neurons from diverse neurogenic origins in Drosophila.

The Drosophila visual system is a powerful model to study the development of neural circuits. Lobula columnar neurons-LCNs are visual output neurons that encode visual features relevant to natural behavior. There are ~20 classes of LCNs forming non-overlapping synaptic optic glomeruli in the brain.

The underappreciated roles of aboveground vertebrates on belowground communities.

In recent decades, evidence of interactions between aboveground and belowground (i.e., soil) subsystems has accumulated.

Wool Fabric with an Improved Durable Biological Resistance Using a Coumarin Derivative.

Wool is the most widely used proteinic natural fiber in the clothing industry by virtue of its versatile properties. Unfortunately, wool, as a natural fiber, is more susceptible to attack by microorganisms and moths, which may cause harm to the fiber and human health. That is why the antimicrobial and mothproof finishing of natural textiles is of prime importance to the textile and clothing industry.

Decarboxylase mediated oxalic acid metabolism is important to antioxidation and detoxification rather than pathogenicity in .

Oxalic acid (OA), an essential pathogenic factor, has been identified in several plant pathogens, and researchers are currently pursuing studies on interference with OA metabolism as a treatment for related diseases. However, the metabolic route in remains unknown. In this study, we describe D-erythroascorbic acid-mediated OA synthesis and its metabolic and clearance pathways in rice blast fungus.