International Journal of Molecular Sciences最新文献

Matrix metallopeptidases (MMPs) are enzymes that, in balance with their inhibitors, play a vital role in extracellular matrix remodelling, particularly during orthodontic tooth movement (OTM). Despite growing interest, significant research is still required to fully comprehend the mechanisms and signalling pathways involved in periodontal ligament remodelling and OTM, particularly those mediated by MMPs. This review explores recent in vitro and in vivo evidence on how specific MMPs-namely, MMP-1, -2, -3, -8, -9, -12, -13, and -14-respond to compressive and tensile forces, regulate collagen degradation, and influence periodontal ligament fibroblast and osteoblast behaviour, ultimately shaping tissue resorption and formation. We also summarize the roles of periodontal ligament cells, hypoxia, the neurovascular and immune systems, and well-known molecules-including receptor activator of nuclear factor kappa β, receptor activator of nuclear factor kappa β ligand, osteoprotegerin, macrophage colony-stimulating factor, tumour necrosis factor α, transforming growth factor, and interleukins-in orchestrating these responses. Finally, we address the clinical relevance of these pathways, highlighting the potential for therapeutic strategies targeting MMPs activity. Overall, this review underscores the pivotal contribution of MMPs to extracellular matrix turnover and tissue adaptation during OTM and suggests that modulating the MMPs/tissue inhibitors of matrix metallopeptidase (TIMPs) balance may enhance orthodontic outcomes.

Creutzfeldt-Jakob disease (CJD) is a rare but devastating neurodegenerative disorder characterized by the pathological misfolding of the cellular prion protein (PrP^C) into the pathogenic isoform-scrapie prion protein (PrP^Sc), ultimately leading to fatal outcomes. Cerebrospinal fluid (CSF) biomarkers play a pivotal role in early diagnosis, longitudinal monitoring, and prognostic assessment, thereby enhancing the clinical management of this challenging disease. This review summarizes the established CSF biomarkers, 14-3-3 protein, tau protein (total tau), phosphorylated tau isoforms, α-synuclein, neurofilament light chain (Nfl), S100B, neuron-specific enolase (NSE), and phosphorylated neurofilament heavy chain (pNFH), highlighting typical sensitivity ranges (14-3-3 ~70-85%; RT-QuIC > 90%) and subtype-dependent performance variation. We further dissect limitations related to assay variability, inter-laboratory cut-off inconsistencies, and reduced specificity in non-prion dementias. Looking ahead, we discuss emerging multi-omics discovery, integration of CSF with blood-based biomarkers and imaging signatures, and AI-enabled diagnostic modeling. We propose a three-tier biomarker framework combining Real-Time Quaking-Induced Conversion (RT-QuIC) as a confirmatory assay, tau/NfL/pNFH as injury-severity indicators, and multi-omics-derived signatures for early detection and prognosis stratification.

The fall armyworm, Spodoptera frugiperda, has become one of the most damaging agricultural pests worldwide, yet the genetic basis of its extraordinary adaptability remains elusive. Recent studies have highlighted the pivotal role of newly evolved genes in adaptive evolution, and phylostratigraphy has emerged as a powerful conceptual framework to trace their origins. Here, we adopt this framework to investigate how new genes have contributed to the rapid adaptive evolution of S. frugiperda. Using high-quality genomic data, we inferred gene ages across evolutionary phylostrata and identified 277 newly evolved genes that originated after the divergence of Spodoptera. These new genes exhibit hallmark genomic signatures of recent origin, including shorter coding regions, simplified structures, and relaxed evolutionary constraints. Interestingly, transcriptomic analyses revealed strong tissue specificity, with pronounced enrichment in the antenna and brain, indicating possible involvement in chemosensory and neural functions essential for environmental and behavioral adaptation. Under diverse environmental challenges such as pesticide and parasitoid wasp exposure, and virus infection, we found many of the new genes acted as hubs in the regulatory networks associated with pesticide response. Together, our findings suggest that the emergence of new genes has played a critical role in shaping the rapid adaptive evolution of S. frugiperda and provide broader insights into how newly evolved genes contribute to species adaptation.

Previous haplotype Genome Wide Association Studies (GWASs) have suggested several rare loci with a shared increased risk of colorectal, gastric, and prostate cancer. This study aimed to find out more about markers specifically addressing the shared risk of colorectal and gastric cancer, as well as the shared risk of colorectal and prostate cancer. One analysis used 426 colorectal cancer cases with gastric cancer, with no prostate cancer cases in their families, and another analysis used 324 colorectal cancer cases with prostate cancer but no gastric cancer among relatives. The computational program PLINK v1.07 was used for the analysis and for the calculation of corresponding ORs, standard errors, and 95% confidence intervals (CI). The study found support for the loci from previous studies and many new loci with a shared risk of colorectal cancer and gastric cancer. There were no significant loci from the second analysis for a shared risk of colorectal and prostate cancer. Altogether, more than 100 new loci with a shared risk of colorectal cancer and gastric cancer were suggested. A shared risk of colorectal and prostate cancer at some loci could not be ruled out. Haplotype GWAS has again demonstrated its ability to find rare risk loci mostly associated with coding genes.

Patients with inflammatory bowel disease (IBD) frequently fail to achieve protective immunity after hepatitis B vaccination, even with intensified vaccination schedules. In this observational real-world study, 18 patients with IBD who were seronegative for hepatitis B virus (HBV) received three standard doses of the Engerix-B^® vaccine (at 0, 1, and 6 months). After immunisation, patients were classified into responders and non-responders according to their serological response. Blood samples were collected before the first dose and after completion of the vaccination schedule. Responders activated pathways that supported durable protection, including conventional dendritic cells type 1 mobilisation, expansion of IgG plasmablasts, and preservation of B- and T-cell memory. In contrast, non-responders displayed a more inflammatory innate profile, characterised by enrichment of CCR2⁺ monocytes. They also showed higher baseline Treg frequencies, which may suppress effective effector responses, together with impaired natural killer (NK) activation and progressive loss of memory potential. This study shows that hepatitis B vaccine failure in inflammatory bowel disease reflects a convergence of excessive immune regulation, inflammatory activation, and loss of memory potential, underscoring that no single pathway can explain the impaired response.

Hepatitis B virus (HBV) persists in infected hepatocytes through covalently closed circular DNA (cccDNA), a stable episomal form that serves as the transcriptional template for viral replication. Accurate and sensitive quantification of intrahepatic cccDNA is crucial for evaluating antiviral therapies, particularly those targeting a functional cure. Here, we report the development of a novel, cccDNA-specific detection system combining recombinase polymerase amplification (RPA) with CRISPR/Cas12a-based fluorescence detection. We designed and validated CRISPR RNAs (crRNAs) targeting HBV cccDNA-specific regions conserved across genotypes A-D. Reaction conditions for both RPA and Cas12a detection were optimized to enhance sensitivity, specificity, and accuracy. The system reliably detected as few as 10 copies of cccDNA-containing plasmid per reaction and showed no cross-reactivity with non-cccDNA forms in serum or plasma, indicating assay specificity. When applied to liver tissue samples from 10 HBV-infected and 6 non-HBV patients, the RPA-CRISPR/Cas12a assay exhibited a high sensitivity (90%) and a strong correlation with qPCR results (R² = 0.9155), confirming its accuracy. In the conclusion, the RPA-CRISPR/Cas12a system provides a robust, cost-effective, and scalable platform for sensitive and specific quantification of intrahepatic HBV cccDNA. This method holds promises for research and high-throughput therapeutic screening applications targeting cccDNA clearance.

Genetic diversity and kinship information of cotton germplasm resources are fundamental to breeding, providing a theoretical basis for the rational selection of hybrid parents and further breeding of new varieties with high yield, high quality, and multi-resistance. This study utilized cotton varieties that have been used for variety improvement or are widely planted in the Northern Xinjiang cotton region as materials. Genotyping was performed using the ZJU CottonSNP40K chip to analyze genetic diversity and kinship relationships. A total of 26,852 high-quality SNP markers were obtained, including 15,222 SNPs in subgenome A and 11,630 SNPs in subgenome D. The number of SNPs per chromosome ranged from 547 (A04) to 2168 (A08). Based on phylogenetic tree and principal component analysis, the 83 materials were clustered into 3 major subgroups. Group I contained varieties introduced from the former Soviet Union and the United States, which have become important parents for cotton breeding in Northern Xinjiang. Among them, as many as 27 varieties were derived and selected from the introduced US variety 'Beiersinuo' as a parent. While playing an important role in cotton breeding in Northern Xinjiang, this has also led to the current situation where the genetic base of Northern Xinjiang varieties is relatively narrow (average kinship coefficient 0.72). It clarifies the significant role of introduced American variety 'Beiersinuo' in the breeding of Northern Xinjiang cultivars and provides theoretical guidance for broadening the genetic base of Northern Xinjiang cotton varieties.

Photodynamic therapy is a cancer treatment that relies on a photosensitizer (PS) to generate reactive oxygen species upon light activation, thereby destroying cancer cells. The photophysical properties of porphyrins make them effective PSs, while nanoparticles (NPs) enhance their delivery and stability. The bioavailability and targeting efficiency of NPs-PS complexes may be improved through transport via human serum albumin (HSA). This study investigates the HSA binding affinity with 5,10,15,20-(Tetra-4-carboxyphenyl)porphyrin (TCPP) and with TiO₂-TCPP complexes. The interactions were analyzed using UV-Vis absorption, laser-induced fluorescence (LIF), and FTIR spectroscopy. Molecular docking was performed and provided consistent binding constant values for the TCPP-HSA complex with UV-Vis absorption measurements. LIF data revealed a slightly lower affinity when compare free porphyrin with TiO₂-TCPP, possibly due to competitive binding between TiO₂ and HSA. Docking simulations indicated that TCPP favorably interacts with amino acid residues located in subdomains IB and IIIA of HSA, supporting a preferential binding near Sudlow site I. FTIR measurements revealed conformational changes in HSA for both its interactions with TCPP and TiO₂-TCPP, including alterations in α-helical content and reorganization of the hydrogen bonding network within the polypeptide backbone.

As a cornerstone of global agriculture, maize (Zea mays) is a crucial component of sustainable food systems and industrial uses. However, global agricultural production faces pressures from climate change, resource scarcity, and rising nutritional demands. To adapt to changes in their environment, plants evolved precise and sophisticated gene expression regulatory mechanisms. A majority of gene expression regulatory elements are located in promoters and untranslated regions of mRNA. This review aims to elucidate how promoters and 5' untranslated regions function in complex synergy to regulate gene expression in maize. We discuss the structural organization of these regulatory elements, from their basic components to their integrated roles in shaping plant gene expression. Particular emphasis is placed on their significant impact on maize biotechnology, including strategies for controlling, fine-tuning, and enhancing gene expression for crop improvement. With this review we wish to guide future biotechnological innovations and food security.

Vitamin D is a steroid hormone whose relevant immunomodulatory role has been widely described. Therefore, its contribution to the pathogenesis of immune-mediated diseases is an important and ongoing matter of research. Specifically, the active form of vitamin D, i.e., 1,25-dihydroxyvitamin D, through the interaction with its receptor, exerts different activities on the innate and adaptive immune system, among which are suppression of inflammation and promotion of tolerogenic responses. Indeed, vitamin D insufficiency/deficiency has been related to the pathogenesis and/or disease activity of several autoimmune diseases, including, amongst others, multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, and type 1 diabetes mellitus. Based on these premises, in this review, we will describe the main molecular mechanisms modulated by vitamin D in the regulation of immune responses, including the induction of immune tolerance. Moreover, we will focus on the current knowledge regarding the contribution of vitamin D depletion to the aforementioned autoimmune diseases, seeking to provide evidence as to why its supplementation in the context of these immune-mediated disorders may potentially ameliorate disease activity and its related clinical manifestations.