A genome-wide association study identified PRKCB as a causal gene and therapeutic target for Mycobacterium avium complex disease.

Non-tuberculous mycobacterial pulmonary disease (NTM-PD) is a chronic progressive lung disease that is increasing in incidence. Host genetic factors are associated with NTM-PD susceptibility. However, the heritability of NTM-PD is not well understood.

Targeted internalization and activation of glycosidic switch liposomes by a biological macromolecule mPEG×EphA2 increases therapeutic efficacy against lung cancer.

Glycosidic switch liposome (GSL) technology efficiently encapsulates and stabilizes potent anticancer drugs in liposomes using a reversible glucuronide ester. Enzymatic hydrolysis of the glucuronide switch in target cell lysosomes produces parental drug. Our study examined the potential of a bispecific macromolecule, a polyethylene glycol (PEG) engager (mPEG×EphA2), generated by fusing a humanized anti-methoxy PEG (mPEG) Fab with an anti-EphA2 single-chain antibody, to increase GSL uptake into cancer cells and boost the anticancer activity by targeting PEG on GSL and an internalizing tumor antigen.

3D Imaging Resolves Human Pancreatic Duct-β-Cell Clusters During Cystic Change.

Pancreatic cystic changes in adults are increasingly identified through advanced cross-sectional imaging. However, the impact of initial/intra-lobular epithelial remodeling on the local β-cell population remains unclear. In this study, we examined 10 human cadaveric donor pancreases (tail and body regions) via integration of stereomicroscopy, clinical H&E histology, and 3D immunohistochemistry, identifying 36 microcysts (size: 1.

Correction: Lin et al. ATF3-Expressing Large-Diameter Sensory Afferents at Acute Stage as Bio-Signatures of Persistent Pain Associated with Lumbar Radiculopathy. 2021, , 992.

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Core factor of NEXT complex, ZCCHC8, governs the silencing of LINE1 during spermatogenesis.

The overactivation of transposable elements (TEs) is a significant threat to male reproduction, particularly during the delicate process of spermatogenesis. Here, we report that zinc finger protein ZCCHC8-a key component of the nuclear exosome targeting (NEXT) complex that is involved in ribonucleic acid (RNA) surveillance-is required for TE silencing during spermatogenesis. Loss of ZCCHC8 results in delayed meiotic progression and reduced production of round spermatids (RS).

Aldehyde dehydrogenases as drug targets for cancer: SAR and structural biology aspects for inhibitor design.

Aldehydes are organic compounds containing a carbonyl group found exogenously or produced by normal metabolic processes and their accumulation can lead to toxicity if not cleared. Aldehyde dehydrogenases (ALDHs) are NAD(P)-dependent enzymes that catalyze the oxidation of such aldehydes and prevent their accumulation. Along with this primary detoxification function, the known 19 human isoforms of ALDHs, which act on different substrates, are also involved in various physiological and developmental processes.

Lactylation as a post-translational regulator of cGAS and immunity.

In a recent paper at Nature, Li et al. reported that alanine-tRNA synthetases AARS1 and AARS2 are lactate sensors and mediate lactylation of cGAS, leading to its inactivation.

Discovery of novel TANK-Binding Kinase 1 (TBK1) inhibitor against pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) has limited treatment options, underscoring the urgent need for developing new therapies. The upregulation of TBK1 activity plays a crucial role in multiple pancreatic cancer-related signaling pathways, suggesting that inhibiting the kinase activity of TBK1 could be a promising strategy. Herein, we discovered a novel TBK1 inhibitor, LIB3S0280, using a structure-based virtual screening (SBVS) strategy.

From emergence to endemicity of highly pathogenic H5 avian influenza viruses in Taiwan.

A/goose/Guangdong/1/96-like (GsGd) highly pathogenic avian influenza (HPAI) H5 viruses cause severe outbreaks in poultry when introduced. Since emergence in 1996, control measures in most countries have suppressed local GsGd transmission following introductions, making persistent transmission in domestic birds rare. However, geographical expansion of clade 2.

Combinatorial leaky probiotic for anticancer immunopotentiation and tumor eradication.

Combination therapies present a compelling therapeutic regimen against the immunosuppressive and heterogeneous microenvironment of solid tumors. However, incorporating separate therapeutic modalities in regimen designs can be encumbered by complex logistical, manufacturing, and pharmacokinetic considerations. Herein, we demonstrate a single-vector combinational anticancer therapy using an lpp gene knockout leaky probiotic for simultaneous secretion of immunotherapeutic and oncolytic effector molecules.

Intranasal booster with SARS-CoV-2 RBD protein fused to E. coli enterotoxin a subunit after primary mRNA vaccination in mice.

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019 led to the coronavirus infection diseases 2019 (COVID-19) pandemic, significantly impacting global public health and the economy. Numerous COVID-19 vaccines based on the receptor binding domain (RBD) of SARS-CoV-2 spike protein have been developed, utilizing various protein expression platforms and adjuvant systems. In a previous study, we reported using the direct fusion of the A subunit of type IIb E.

Metabolic dysregulation in Huntington's disease: Neuronal and glial perspectives.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by a mutant huntingtin protein with an abnormal CAG/polyQ expansion in the N-terminus of HTT exon 1. HD is characterized by progressive neurodegeneration and metabolic abnormalities, particularly in the brain, which accounts for approximately 20 % of the body's resting metabolic rate. Dysregulation of energy homeostasis in HD includes impaired glucose transporters, abnormal functions of glycolytic enzymes, changes in tricarboxylic acid (TCA) cycle activity and enzyme expression in the basal ganglia and cortical regions of both HD mouse models and HD patients.

Current landscape of mRNA technologies and delivery systems for new modality therapeutics.

Realizing the immense clinical potential of mRNA-based drugs will require continued development of methods to safely deliver the bioactive agents with high efficiency and without triggering side effects. In this regard, lipid nanoparticles have been successfully utilized to improve mRNA delivery and protect the cargo from extracellular degradation. Encapsulation in lipid nanoparticles was an essential factor in the successful clinical application of mRNA vaccines, which conclusively demonstrated the technology's potential to yield approved medicines.

Neuroprotective effects of intranasal extracellular vesicles from human platelet concentrates supernatants in traumatic brain injury and Parkinson's disease models.

Background: The burgeoning field of regenerative medicine has significantly advanced with recent findings on biotherapies using human platelet lysates (HPLs), derived from clinical-grade platelet concentrates (PCs), for treating brain disorders. These developments have opened new translational research avenues to explore the neuroprotective effects of platelet-extracellular vesicles (PEVs). Their potential in managing neurodegenerative conditions like traumatic brain injury (TBI) and Parkinson's disease (PD) warrants further exploration.

Causal Mediation Analyses for the Natural Course of Hepatitis C: A Prospective Cohort Study.

Background: Hepatitis C virus (HCV) infection is a systemic disease. However, the relative contribution of intrahepatic and extrahepatic diseases to mediating HCV-induced mortality is unclear, albeit critical in resource allocation for reducing preventable deaths. To this end, this study comprehensively quantified the extent to which intrahepatic and extrahepatic diseases mediate HCV-induced mortality.

Association between situs inversus and maternal SARS-CoV-2 infection at gestational age 4-6 weeks.

Background: A dramatic increase in fetal situs inversus diagnoses by ultrasound in the months following the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) surge of December 2022 in China led us to investigate whether maternal SARS-CoV-2 exposure could be associated with elevated risk of fetal situs inversus.

Methods: In this multi-institutional, hospital-based, matched case-control study, we investigated pregnant women who underwent ultrasonographic fetal biometric assessment at gestational weeks 20-24 at our hospitals. Each pregnant woman carrying a situs inversus fetus was randomly matched with four controls based on the date of confinement.

Molecular Mechanism of pH-Induced Protrusion Configuration Switching in Piscine Betanodavirus Implies a Novel Antiviral Strategy.

Many viruses contain surface spikes or protrusions that are essential for virus entry. These surface structures can thereby be targeted by antiviral drugs to treat viral infections. Nervous necrosis virus (NNV), a simple nonenveloped virus in the genus of betanodavirus, infects fish and damages aquaculture worldwide.

Multivalent mRNA Vaccine Elicits Broad Protection against SARS-CoV-2 Variants of Concern.

SARS-CoV-2 new waves are primarily caused by changes to the spike protein (S), which can substantially decrease the efficacy of vaccines. Therefore, we tested several multivalent mRNA-LNP vaccines, targeting the full-length S proteins of different variants, and identified an optimal combination for protection against VOCs in BALB/c mice. The tested formulations included trivalent (WT + BA.

Plasma SCUBE2 as a novel biomarker associates with survival outcomes in patients with sepsis-associated acute kidney injury.

Background: The adverse effects of sepsis-associated acute kidney injury (SA-AKI) highlight the need for new biomarkers. Signal Peptide-Complement C1r/C1s, Uegf, Bmp1-Epidermal Growth Factor-like Domain-Containing Protein 2 (SCUBE2), important for angiogenesis and endothelial integrity, has been linked to increased mortality in models of lipopolysaccharide-induced lung injury. This research aimed to assess the utility of plasma SCUBE2 levels as a prognostic indicator for SA-AKI in intensive care unit (ICU) patients.

Performance evaluation of predictive models for detecting MMR gene mutations associated with Lynch syndrome in cancer patients in a Chinese cohort in Taiwan.

Identifying Lynch syndrome significantly impacts cancer risk management, treatment, and prognosis. Validation of mutation risk predictive models for mismatch repair (MMR) genes is crucial for guiding genetic counseling and testing, particularly in the understudied Asian population. We evaluated the performance of four MMR mutation risk predictive models in a Chinese cohort of 604 patients with colorectal cancer (CRC), endometrial cancer (EC), or ovarian cancer (OC) in Taiwan.