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Glutaminyl-peptide cyclotransferase-like protein (QPCTL) is a newly discovered enzyme that has sparked interest owing to its possible role in cancer genesis and progression. Initially discovered as a post-translational modification regulator of protein maturation, QPCTL has emerged as a key participant in cancer biology. Recent research has linked QPCTL to numerous essential cancer-related processes, including cell proliferation, migration, invasion, and apoptosis. Furthermore, QPCTL expression changes have been seen in a variety of cancer types, underlining its potential as a diagnostic and prognostic marker. The molecular mechanisms behind QPCTL's participation in cancer will be examined in this review. We investigate its involvement in the control of signaling pathways and the modification of cellular activities that are important in cancer. We also examine the clinical importance of QPCTL, including as its relationship with tumor development, metastasis, and response to treatment. We also discuss the possible therapeutic implications of targeting QPCTL in cancer therapy. QPCTL is a prospective target for the development of innovative anticancer treatments due to its participation in several cancer-associated pathways.

Aspergillus species produce polyketides, which form the basis of aflatoxins, some of the most significant mycotoxins in agriculture. Aflatoxins contaminate cereals, oilseeds, and nuts, both in the field and during storage. Of the 13 naturally occurring aflatoxins, the most potent are aflatoxins B₁, B₂, G₁, and G₂. The primary aflatoxigenic species are A. flavus, A. parasiticus, and A. nomius, while A. arachidicola, A. minisclerotigenes, and A. saccharicola also documented. These aflatoxin producers belong to three sections- 'Flavi', 'Ochraceorosei', and 'Nidulantes.' Aspergillus flavus, within section Flavi, shows morphological diversity, classified into Group I (S- and L- strains) and Group II (S- strains), with S-strains producing higher levels of aflatoxins. Aflatoxin biosynthesis is primarily regulated by the aflR gene, though other genes like aflS, aflP, aflQ, aflC, and aflM are also associated. However, presence of the aflR gene does not guarantee aflatoxin production across species. Sterigmatocystin serves as a precursor molecule within the pathway leading to aflatoxin production. Phylogenetic assessment, using ITS, BenA, CaM, and RBP2 gene sequences, reveals distinct clusters within Aspergillus sections and highlights the co-evolution of aflatoxigenic and non-aflatoxigenic species. Aspergillus ochraceoroseus and A. rambellii diverged out of aflatoxin-producing species earlier in evolutionary history, before splitting from a shared ancestor with A. fumigatus, which neither produces aflatoxins nor sterigmatocystin. Non-aflatoxigenic species like A. oryzae may evolve from aflatoxigenic species like A. flavus due to variations in evolutionary rates, telomere deletions, and mutations in aflatoxin biosynthesis genes. Comparative genomic analysis of AF, AF/ST and ST gene cluster shows that A. flavus has a larger aflatoxin gene cluster, while A. ochraceoroseus lacks the genes aflP and aflQ. Additionally, A. ochraceoroseus and A. rambellii possess a smaller genome, suggesting that genetic drift and deletions have refined their genomes for more efficient aflatoxin production.

Objective: This study aims to find the gene expression profile specifically in basal cells from pulmonary acute respiratory distress syndrome (ARDSp) patients using single-cell level analysis.

Methods: Single nuclear RNA sequencing (snRNA-seq) data of lung samples, including 18 ARDSp participants and 7 healthy participants, were sourced from the GEO database (GSE171524). The differentially expressed genes (DEGs) were screened by | log2FC | >1 and P < 0.05. Functional enrichment was constructed via Gene Ontology (GO) analysis. Pathway enrichment was conducted via Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The protein-protein interaction (PPI) network of the DEGs was performed via the STRING database. Cytoscape software was employed to find hub genes. The hub genes were sequenced and validated via data set after constructing the rat model of ARDSp.

Results: Using DESeq2 package, 299 genes were disclosed to be downregulated, while 228 were upregulated in ARDSp participants. GO analysis disclosed DEGs were enriched in processes like actin filament organization, regulation of small GTPase-mediated signal transduction, response to unfolded protein, wound healing, and response to oxygen levels. Meanwhile, KEGG analysis disclosed DEGs were involved in protein digestion and absorption, Th17 cell differentiation, iron death, and other biological effects. Ten hub genes, including FN1, HIF1A, HSP90AA1, SMAD3, FOS, CDKN2A, COL1A1, HSPA8, FLNA, and NFKBIA were highlighted based on their network centrality and biological significance. HIF1A, HSPA8, NFKBIA, and CDKN2A were differentially expressed in the validation dataset.

Conclusions: Basal cells in ARDSp exhibit significant changes in gene expression, with ten hub genes identified. Among them, four (HIF1A, HSPA8, NFKBIA, CDKN2A) were validated experimentally using RNA-Seq data from an ARDSp rat model. This study emphasizes the role of basal cells in ARDSp, highlighting the altered gene networks involved in repair and inflammatory responses, providing potential targets for further therapeutic exploration. These findings suggest that alterations in these hub genes may be crucial to basal cell-driven inflammatory and reparative responses in ARDSp.

Understanding the early stages of human congenital myopathies is critical for proposing strategies for improving musculoskeletal muscle performance, such as restoring the functional integrity of the cytoskeleton. SH3 and cysteine-rich domain 3 (STAC3) are proteins involved in nutrient regulation and are an essential component of the excitation-contraction (EC) coupling machinery for Ca²⁺ releasing. A mutation in STAC3 causes debilitating Native American Myopathy (NAM) in humans, while loss of this gene in mice and zebrafish (ZF) results in premature death. Clinically, NAM patients demonstrated increased lipids in skeletal muscle, but it is unclear if neutral lipids are associated with altered muscle function in NAM. Using a CRISPR/Cas9 induced stac3^-/- knockout (KO) zebrafish model, we determined that loss of stac3 leads to delayed larval hatching which corresponds with muscle weakness and decreased whole-body Ca²⁺ level during early skeletal development. Specifically, we observed defects in the cytoskeleton in F-actin and slow muscle fibers at 5 and 7 days post-fertilizations (dpf). Myogenesis regulators such as myoD and myf5, mstnb were significantly altered in stac3^-/- larvae. These muscle alterations were associated with elevated neutral lipid levels starting at 5 dpf and persisting beyond 7 dpf. Larva lacking stac3 had reduced viability with no larva knockouts surviving past 11 dpf. This data suggests that our stac3^-/- zebrafish serve as an alternative model to study the diminished muscle function seen in NAM patients. The data gathered from this new model over time supports a mechanistic view of lipotoxicity as a critical part of the pathology of NAM and the associated loss of function in muscle.

Fabry disease (FD) is a lysosomal storage disorder resulting from mutations in the alpha-galactosidase A (GLA) gene, characterized by pain, skin lesions, renal failure, and cardiac disease. A 60-year-old proband was hospitalized for recurrent atrial fibrillation (AF) that was unresponsive to medication, with cardiac magnetic resonance imaging (CMRI) revealing left ventricular wall hypertrophy and fat infiltration. Whole-exome sequencing (WES) did not reveal any suspicious pathogenic variants. To further assess the diagnosis, endomyocardial biopsy (EMB) and electron microscopy were performed, revealing abundant zebra bodies in cardiomyocytes, consistent with FD. The diagnosis was ultimately confirmed by GLA enzyme activity analysis (<1.00). Further genetic investigations identified a deep intronic variant (c.640-814T>C) within the GLA gene. Minigene experiments demonstrated that this variant affected the splicing of GLA, resulting in the production of a truncated protein (p.Pro214SerfsTer10). Western blotting (WB) showed that the truncated protein was retained, while immunofluorescence (IF) analysis indicated partial lysosomal localization. In vitro assays confirmed that the retained protein was non-functional and exerted a dominant-negative effect on the normal GLA protein. Molecular docking analysis further revealed that the truncated protein could bind to the wild GLA monomer, significantly reducing cellular GLA enzyme activity. These findings indicate that, beyond being non-functional, the c.640-814T>C mutation may also exerts a dominant-negative effect that impairs the function of the wild GLA protein. These results highlight the importance of recognizing deep intronic mutations in the diagnosis and treatment of FD, contributing to a deeper understanding of the molecular mechanisms, enriching mutation databases, and providing insights into genotype-phenotype correlations.

Objectives: The aim is to analyze differentially expressed genes (DEGs) in mice with sepsis-related intestinal mucosal barrier damage and to explore the diagnostic and protective mechanisms of this condition at the transcriptome level.

Methods: Small intestinal tissues from healthy male C57BL/6J mice subjected to Cecal ligation and puncture (CLP) and sham operation were collected. High-throughput sequencing was performed using the paired-end sequencing mode of the Illumina HiSeq platform. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted on the differentially expressed genes (DEGs). A protein-protein interaction (PPI) network was constructed using the STRING database, and hub genes were identified with Cytoscape. These hub genes were then validated using quantitative real-time polymerase chain reaction (RT-qPCR).

Results: A total of 239 DEGs were identified, with 49 upregulated and 130 downregulated genes. KEGG enrichment analysis showed that these DEGs were primarily involved in cytokine-cytokine receptor interaction, Th1 and Th2 cell differentiation, viral protein interactions with cytokines and their receptors, and the IL-17 signaling pathway. The top 10 hub genes were selected using the cytoHubba plugin. Experimental validation confirmed that the expression levels of TBX21, CSF3, IL-6, CXCR3, and CXCL9 matched the sequencing results.

Conclusion: TBX21, CSF3, IL-6,CXCR3, and CXCL9 may be potential biological markers for the diagnosis and treatment the sepsis-associated intestinal mucosal barrier.

Fabricating suitable porous carbon materials that are simultaneously applied in various electrochemical energy storage (EES) systems including supercapacitors (SCs) and lithium-ion capacitors (LICs) has an important significance in meeting the increasing demands in high energy density, high power density along with ultra-long life. Herein, cubic hierarchical porous carbon (CHPC) with abundant micro-mesoporous structures and moderate S, N co-doped atoms has been rationally designed by using MgO cubes as the templates and waste tire pyrolysis oil (WTPO) as carbon source and dopant. Attributed to the unique microstructures, the CHPC materials have been successfully utilized in different EES systems. In the aqueous electrolyte system, the assembled CHPC-2//CHPC-2 with 2 mg cm^-2 delivered high specific capacitance of 199.0 at 1 A/g, along with 98.5 % capacity retention rate for 20,000 cycles at 6 A/g. Even at high mass loading of 12 mg cm^-2, CHPC-12//CHPC-12 still can deliver high gravimetric and areal capacitances of 187.0 F g^-1 and 2.24 F cm^-2 at 10 A/g, showing an excellent high-loading performance. Even under extreme conditions of -40 and 60 °C, the assembled SCs still can deliver an ultrahigh capacity retention rate of 97.9 % and 100 % at 10 A/g for 2000 and 8000 cycles, respectively. In addition, the symmetric CHPC//CHPC LICs also have been assembled and displayed a maximal energy density of 133.5 Wh Kg^-1 at 1178.2 W Kg^-1. This work provides new insight into the high-value utilization of WTPO for prepared porous carbon with excellent electrochemical performance in various EES systems.

A dispersive solid phase extraction method using new magnetic nanoparticles based on nickel ferrite was introduced for the extraction of six triazole pesticides (penconazole, hexaconazole, tebuconazole, diniconazole, triadimefon, and difenoconazole) from water samples before liquid chromatography-tandem mass spectrometry analyses. Initially, a new deep eutectic solvent was synthesized with 1,2,4-triazole and n-octanol for surface modification of the nanoparticles easily achieved through microwave radiation. The nanoparticles morphology, magnetic properties, adsorption capacity, isotherms, and crystalline patterns of the sorbent were examined. The capability of the sorbent was evaluated by extracting the target pesticides from water samples showing significant differences in adsorption capacity and efficiency between the modified and non-modified nanoparticles. High extraction recoveries (68-86 %) were achieved for the analytes using small amounts of the sorbent with low limits of detection (0.03-0.08 ng mL^-1) and quantification (0.13-0.29 ng mL^-1), a wide linear range (0.29-250 ng mL^-1), and acceptable precision (relative standard deviations ≤6.9 %).