Cocadviroid rimocitri (citrus bark cracking viroid, CBCVd) diagnostic surveys were carried out from July 2022 to August 2024 in major pistachio (Pistacia vera L.) growing locations of Southeast Anatolia region (Türkiye). Dormant shoots, green twigs, and leaves were collected from a total of 223 symptomatic and asymptomatic trees in 51 pistachio orchards and tested by RT-PCR to investigate the presence of the viroid. CBCVd incidence was about 19.7% out of all tested samples. Full length sequences of CBCVd-pistachio isolates ranged from 282 to 286 nucleotides. They had considerable sequence variation, with 14 distinct haplotypes, resulting in a haplotype diversity of 0.925. Overall, the estimated average number of nucleotide differences (k) and nucleotide diversity (π) were 5.16 and 0.019, respectively. These findings indicate that the CBCVd in tested pistachio trees comprised a heterogeneous population. The nucleotide sequence homology was 96-100% among themselves, and they were most closely related to isolate W11 from pistachio (MF198463). The pathogenicity of these CBCVd-pis variants was demonstrated in cucumber seedlings, and viroid transmission to four healthy rootstocks (P. vera cv. 'Siirt,' P. atlantica, P. khinjuk, and UCB1). Symptom expression on cucumber seedlings was recorded after 20-day post-inoculation. Graft uptake was significantly reduced when viroid-infected buds were grafted onto all rootstocks.

Platelet-derived growth factor subunit B (PDGFB) is a key regulator of vascular remodeling, angiogenesis, and blood-brain barrier integrity. Although elevated PDGFB levels have been reported after ischemic injury, whether stroke liability itself causally influences circulating PDGFB levels remains unclear. We performed a two-sample Mendelian randomization (MR) analysis to assess the causal effects of genetically predicted all stroke, ischemic stroke, and cardioembolic stroke on plasma PDGFB concentrations. Genetic instruments were obtained from large-scale GIGASTROKE genome-wide association studies, and outcome data were derived from a proteomics GWAS. Instruments were then filtered by removing variants associated with established cardiovascular risk factors in a phenome-wide screen and outliers identified by RadialMR. The inverse variance-weighted (IVW) method was used as the primary analysis, complemented by weighted median, weighted mode, and MR-Egger approaches. Sensitivity analyses included Cochran's Q statistics, MR-Egger intercept tests, single-SNP analyses, leave-one-out analyses, and MR-PRESSO. IVW analysis demonstrated a significant positive causal association between genetic liability to all stroke and plasma PDGFB levels (β = 0.209, SE = 0.062, 95% CI 0.088 to 0.331, p = 7.3 × 10[-4]). A similar association was observed for ischemic stroke (β = 0.155, SE = 0.059, 95% CI 0.039 to 0.270, p = 0.009), with directionally consistent results across sensitivity analyses. MR-Egger regression for ischemic stroke initially suggested pleiotropy.After removal of a radial-MR outlier (rs2289252), the intercept was attenuated and no longer statistically significant (- 0.0190, p = 0.282). In contrast, no evidence of a causal association was found between cardioembolic stroke liability and plasma PDGFB levels across all MR methods (β = - 0.078, SE = 0.087, 95% CI - 0.248 to 0.092, p = 0.368). These findings provide genetic evidence that liability to stroke, particularly ischemic stroke, is causally associated with increased circulating PDGFB levels, whereas cardioembolic stroke does not show such an effect. This suggests that elevated PDGFB reflects vascular responses specific to ischemic stroke rather than a general consequence of all stroke subtypes.

Autism Spectrum Disorder (ASD) involves Mirror Neuron System (MNS) dysfunction, driving core social and imitative impairments. Systemic physiological alterations such as autonomic dysregulation, mitochondrial dysfunction and neuroinflammation are known to impair synchronization and plasticity of neuronal clusters. A less-evident environmental cofactor, coinciding with rising ASD prevalence, is the considerable world-wide increase in electromagnetic radiation (EMR) overall exposure among children. Experimental evidence shows how low-intensity EMR influences cellular processes, via voltage-gated calcium channels (VGCCs), oxidative stress, and mitochondrial metabolism. The Resonant Convergence framework, allow to predict how chronic EMR exposure during the first 24 postnatal months of life can act as a factor in ASD pathogenesis. The best candidate mechanism is chronic Ion Cyclotron Resonance (ICR) detuning the Ca[2+]-calmodulin pathway, thus disrupting MNS synchronization.

Vascular remodeling within the developing fetus and placenta is essential for supporting the growth and function of emerging tissues and organs. Pericytes (PCs) play a central role in stabilizing and maturing microvascular networks by extending along endothelial cells (ECs) and reinforcing vessel integrity. In the placenta, as in other organs, PC-EC communication is mediated in part by platelet-derived growth factor-BB (PDGF‑BB) signaling, which governs PC differentiation, proliferation, migration, and survival, ultimately enabling their recruitment and retention along capillaries. In this study, we identified progressive PC investment along feto‑placental capillaries in both murine and human tissues across gestation, supported by morphological and molecular evidence. Placental PCs displayed phenotypic heterogeneity comparable to that observed in the brain and heart, suggesting conserved diversity across organ systems. In addition to characterizing PC dynamics, we examined the expression of recently identified soluble PDGF Receptor-β (sPDGFRβ) isoforms. These variants were detected at the protein and transcript levels in mouse and human placentas, as well as in a murine trophoblast‑embryonic stem cell (TESC) differentiation model that recapitulates aspects of early placental vascular development. Within this model, sPDGFRβ expression was independent of ADAM10 activity and exogenous growth factors during early vessel formation but was markedly upregulated during hypoxia. To assess how elevated sPDGFRβ might influence PDGF‑BB signaling, we exposed TESC‑derived vascular networks to excess PDGF‑BB with or without a sPDGFRβ mimetic. PDGF‑BB alone reduced full‑length PDGFRβ levels while increasing receptor phosphorylation, consistent with known ligand‑induced regulatory mechanisms. Inclusion of the sPDGFRβ mimetic shifted these responses toward baseline, suggesting a potential modulatory or feedback role for soluble receptor variants. Together, these findings demonstrate that PCs are progressively recruited to placental capillaries and exhibit diverse phenotypes during development, and that soluble PDGFRβ isoforms may modulate PDGF‑BB signaling in a manner sensitive to oxygen tension. Understanding these mechanisms provides insight into the regulation of placental vascular maturation and may inform strategies to improve human health by targeting disorders rooted in impaired placental development.

Vascular instability, characterized by impaired pericyte coverage, is a hallmark of tumor progression. ATP6L is highly expressed in colorectal cancer (CRC) tissues and promotes tumor progression by enhancing the tumor microvasculature; however, its direct impact on vascular stability remains unclear. ATP6L expression, microvascular morphology, and pericyte coverage were analyzed by immunohistochemistry in a cohort of 179 CRC specimens, and the role of ATP6L in vascular stability was further investigated by modulating its expression both in vitro and in vivo. In vitro, MC38 and CT26 cells with ATP6L overexpression or knockdown were co-cultured with mouse vascular smooth muscle cells (MOVAS), and MOVAS proliferation, migration, and apoptosis were evaluated using EdU incorporation, transwell migration, and TUNEL staining assays, respectively. PDGFB secretion and PDGFRβ expression were assessed by ELISA, Western blotting, and immunofluorescence. Along the normal colorectal mucosa-adenoma-adenocarcinoma sequence, ATP6L upregulation was closely associated with progressive vascular instability, characterized by loss of pericyte coverage and increasing vascular morphological heterogeneity. Mechanistically, ATP6L overexpression promoted extracellular acidification, suppressed PDGFB secretion, and subsequently reduced PDGFRβ expression in pericytes, thereby impairing their recruitment and survival. Conversely, ATP6L knockdown attenuated extracellular acidification, restored PDGFB/PDGFRβ signaling, and rescued pericyte proliferation, migration, and survival. These findings identify ATP6L as a key mediator of perivascular dysfunction in CRC and demonstrate that ATP6L-induced extracellular acidification disrupts vascular stability by suppressing the PDGFB/PDGFRβ signaling axis and impairing pericyte function.

Severe nitrogen (N) deficiency inhibits crop growth and yield, while low use efficiency of N fertilizer causes resource waste and environmental harm. Enhancing crop N use efficiency (NUE) is thus a critical scientific challenge. Ecofriendly and cost-effective silicon (Si) fertilizer can enhance NUE across the entire soil-plant continuum. Si-mediated improvements in soil physicochemical properties and microbial community structure underlie enhanced mineralization and suppressed denitrification. Si-cell wall interactions support symbiont recognition, nodule initiation, and formation of functional nodules for sustained N2 fixation. Si also upregulates genes encoding N transporters and assimilatory enzymes to improve N uptake, assimilation, and remobilization. This mini-review synthesizes Si's roles in regulating soil N transformation and plant N uptake, assimilation, and remobilization. It aims to support precision Si fertilization strategies that reduce synthetic N input without compromising yield.

Aortic dissection (AD) is a severe vascular condition marked by abrupt onset, rapid progression, and heightened mortality rates. Vascular smooth muscle cells (VSMCs), the predominant cellular component of the arterial media, are essential for maintaining the structural integrity and functionality of blood vessels. Recent studies have associated Cysteine-rich protein 2 (CSRP2) with the advancement of several vascular diseases. The involvement of CSRP2 in AD progression is unclear. Aortic tissues were collected from patients for RNA sequencing and histological analysis. A mouse model of AD was created using β-aminopropionitrile monofumarate (BAPN), while VSMC phenotypic switching was induced by platelet-derived growth factor BB (PDGF-BB). Adeno-associated virus vector was used to overexpress CSRP2 in aorta. A variety of histopathological assays and biochemical analyses were applied to determine gene and protein expression patterns as well as uncover underlying molecular mechanisms. CSRP2 was significantly downregulated in both human and murine AD, and CSRP2 gene overexpression dramatically reduced BAPN-induced AD incidence and prevented animal mortality. CSRP2 could preserve a contractile VSMC phenotype, even though under PDGF-BB stimulation. Mechanistically, our findings reveal that CSRP2 directly interacts with p130 Crk-associated substrate (p130Cas; also known as BCAR1) and reduces its phosphorylation, which in turn inhibits the activation of extracellular signal-regulated kinase (ERK) signaling pathways, thereby preventing VSMC phenotypic switching induced by PDGF-BB. Our findings identify CSRP2 as a novel regulator of VSMC phenotypic modulation and a significant modulator of AD development, suggesting its potential as a target for early intervention for AD.

Structural variants (SVs) are a major yet underused source of adaptive variation in aquaculture. We built a genome-wide SV atlas for 180 Penaeus vannamei from six commercial breeding populations and discovered 1,159,046 SVs, with uneven chromosomal distributions and multi-type hotspots. Over 63.53% of SVs overlapped repeats-especially simple sequence repeats, DNA transposons, and LINEs. SV and SNP densities were highly correlated. Across populations, 482 k SVs were shared and 145,623 were singletons; the fraction of deletions increased from shared to singleton classes. BMK and KH harbored more singletons than SIS, RH, and CP, indicating greater divergence. PCA and ADMIXTURE recovered three major clusters and revealed the substructure in RH, mirroring SNP analyses. Selection scans identified 78-193 sweep windows per population encompassing 38-161 candidate genes. These genes were predominantly enriched in population-specific processes such as chromatin regulation, meiotic recombination, membrane-associated functions, suggesting that structural variants may contribute to divergence in reproductive, metabolic, and structural pathways across breeding programs. Nevertheless, 10 genes showed parallel signals in over 3 populations; many carry short deletions likely affecting regulatory or coding elements. Together, these results show that genome architecture and domestication jointly shape the shrimp SV landscape; that SVs alone robustly resolve population history; and that a small set of recurrent, deletion-bearing regulatory genes may underpin convergent improvement. The SV map and candidate loci provide diagnostic markers for germplasm tracing and candidate loci for marker-assisted or genomic selection in P. vannamei breeding.

Objective To establish an efficient and rapid primary culture protocol for mouse pulmonary artery smooth muscle cell (PASMC). Methods PASMC were isolated from mice using a novel dual-enzyme digestion method. Cell morphology was observed under an inverted phase-contrast microscope, and cell type and purity were identified by immunofluorescence staining for α-smooth muscle actin (α-SMA). Cell growth after passage was assessed using the CCK-8 assay. The migratory response of PASMC to platelet-derived growth factor-BB (PDGF-BB) was evaluated by cell scratch assay. Changes of protein expression in primary PASMC after stimulation of transforming growth factor β1 (TGF-β1) were detected by Western blot. Results Under light microscopy, PASMC showed a long spindle-shaped morphology with a positive rate reaching as high as 98%. The growth curve of passaged cells approximated an "S" shape. Primary cultured PASMC showed a significant migratory response to stimulation of PDGF-BB. TGF-β1 stimulation significantly increased the expression of phospho-Smad2 (p-Smad2) in PASMC. Conclusion The novel dual-enzyme digestion method significantly improves the isolation efficiency and viability of primary PASMC, providing a sufficient and phenotypically stable source of high-quality cells for in vitro studies.

The C. elegans SIK3 homolog KIN-29 regulates the interaction between sleep and metabolism, but mechanisms underlying this regulation are not understood. Here, we show that KIN-29 regulates sleep that is induced by cellular stress (stress-induced sleep or SIS) through mitochondrial reactive oxygen species (ROS) signaling. Following sleep-promoting ultraviolet-C (UVC) irradiation, mitochondrial ROS rises in concert with sleep in wild-type but not in sleepless kin-29 mutants. kin-29 mutants have reduced mitochondrial ROS, reduced oxygen consumption rates, and are resistant to oxidative stress. Transcriptomic and proteomic profiling of kin-29 mutants reveal enrichment for genes involved in ROS mitigation such as the mitochondrial superoxide dismutase SOD-3. Consistent with the notion that ROS promotes sleep, genetic disruption of mitochondrial SODs enhances UVC-induced SIS. Increasing mitochondrial ROS using the optogenetic tool SuperNova partially restores SIS in kin-29 mutants but not in mutants with defective function of the sleep-inducing ALA neuron; this suggests that mitochondrial ROS act downstream of kin-29 but upstream of ALA. The identification of mitochondrial ROS as a nematode sleep regulator supports a phylogenetically conserved mechanism by which metabolic stress and SIKs promote sleep.

Tissue repair depends on how inflammatory cues drive regenerative cell-state transitions; a process poorly understood in human tissues. Human dental pulp provides an accessible, structurally well-defined injury model with robust clinical responses, facilitating in situ investigations of inflammatory signaling and endogenous regeneration. Here, we integrated high-resolution spatial transcriptomics with single-cell RNA sequencing (scRNA-seq) to chart its cellular ecosystem in health and caries. We resolved five major cell classes and four odontoblast progenitor subtypes, reconstructing their differentiation trajectories. Spatial mapping of immune cells combined with cell-cell communication analysis revealed that macrophages promote progenitor migration and odontoblastic differentiation via platelet-derived growth factor B (PDGFB) signaling. Inspired by this axis, we developed a hydrogel that amplifies macrophage PDGFB delivery via adeno-associated virus (AAV) vectors, which promoted mineralization in vitro and accelerated reparative dentin formation in a direct pulp-capping mouse model. Downstream analyses and pathway perturbation further confirmed the role of the PDGFB-Wnt-RUNX2 signaling axis in these progenitors. This study provides a spatially resolved single-cell framework showing how immune cues direct stem/progenitor fate to orchestrate regeneration, offering a targeted design paradigm for pulp regeneration biomaterials.

Rheumatoid arthritis (RA) is characterized by chronic synovial inflammation accompanied by pathological angiogenesis, which contributes to pannus formation and disease progression. However, the upstream mechanisms regulating pathological angiogenesis in RA remain incompletely understood. In this study, bioinformatic analysis of two independent Gene Expression Omnibus (GEO) datasets, immunohistochemical analysis of human synovial tissues, and functional studies using MH7A synovial fibroblasts and HUVEC tube formation assays were performed to investigate the role of WNT1-inducible signaling pathway protein 3 (WISP-3) in RA angiogenesis. WISP-3 expression was consistently elevated in RA synovial tissues compared with healthy controls. Recombinant WISP-3 significantly enhanced endothelial tube formation and increased platelet-derived growth factor-B (PDGF-B) expression in MH7A cells. Mechanistically, WISP-3 activated the PI3K/p85/Akt/mTOR signaling pathway, whereas pharmacological inhibition or siRNA-mediated knockdown of p85, Akt, or mTOR markedly attenuated PDGF-B expression and angiogenic activity. WISP-3 also suppressed hsa-let-7b-5p expression, and restoration of hsa-let-7b-5p using a synthetic mimic significantly reduced WISP-3-induced PDGF-B expression and endothelial tube formation. Luciferase reporter assays further confirmed PDGF-B as a direct target of hsa-let-7b-5p. These findings identify a previously unrecognized WISP-3/p85/Akt/mTOR/hsa-let-7b-5p/PDGF-B signaling axis that promotes pathological angiogenesis and provides new mechanistic insight into synovial vascular remodeling in RA.

Decorin, a proteoglycan shown to inhibit transforming growth factor β1 (TGF-β1) signaling, has been increasingly considered as a potential anti-fibrotic agent to aid in therapies addressing corneal scarring and blindness. Decorin is also known to interact with a wide range of other growth factors, such as platelet-derived growth factor (PDGF), which has been shown to stimulate corneal cell migration to repopulate the decellularized region of the wounded cornea. In other tissues, decorin has been shown to inhibit PDGF-mediated migration and prolong wound healing. However, our understanding of the effect of decorin on PDGF signaling in the corneal stroma environment is limited. Specifically, thus far, there have been no studies investigating the interaction between decorin and PDGF in the context of the uniquely organized fibrillar collagen extracellular matrix (ECM), which provides topographic cues that guide cell migration during wound healing. The purpose of this study is to use an in vitro model of decorin-coated aligned collagen fibrils analogous to the corneal stroma ECM to investigate this interaction. With this in vitro model, we demonstrate that decorin inhibits the response of PDGF-BB-stimulated keratocytes to a 2-dimensional (2D) aligned collagen fibril ECM, reducing cell alignment, motility, PDGF receptor β (PDGFRβ) phosphorylation, and wound closure. We observed that when presented with a decellularized wound region, cells on the decorin-coated substrates migrated more randomly and were less aligned with the underlying aligned collagen fibrils than cells on uncoated fibrils, resulting in slower wound closure. Furthermore, PDGF-BB-stimulated cells on the decorin coating had increased branching and reduced solidity, representing a shift from the elongated, bipolar morphology typically resulting from PDGF-BB treatment towards the stellate, branched keratocyte phenotype. While decorin seems to be an effective agent against TGF-β1-mediated fibrosis, its interaction with PDGF-BB appears to present other challenges to wound healing that should be considered in the development of therapies for healthy corneal wound healing.

While glucose-driven mitochondrial dysfunction has been proposed to promote vascular dysfunction responsible for saphenous vein graft failure (VGF) following bypass surgery, the impact of type 2 diabetes mellitus (T2DM) on mitochondrial function in human saphenous vein smooth muscle cells (HSVSMCs) responsible for maladaptive remodelling is unknown. Our aim was to identify signalling pathways that mediate any mitochondrial dysfunction in HSVSMCs in vitro and assess the impact of T2DM. HSVSMCs explanted from surplus HSV tissues from consenting T2DM and non-diabetic patients undergoing coronary artery bypass graft surgery were treated with known activators and inhibitors of the JAK/STAT and MAPK/ERK pathways. Following this, real-time oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) measures of mitochondrial function were then determined. Our findings revealed that both IL-6/sIL-6Rα trans-signalling complexes and platelet-derived growth factor-BB (PDGF-BB) significantly increased OCR in HSVSMCs from T2DM patients but not non-diabetic controls. Meanwhile, only PDGF-BB increased ECAR in HSVSMCs from T2DM patients but not in non-diabetic controls. The observed increases in OCR and ECAR were abolished by JAK1/2-selective inhibitor ruxolitinib. Furthermore, thrombin caused a significant increase in OCR, specifically in HSVSMCs from T2DM patients, and this effect was abolished by the MEK1/2-selective inhibitor trametinib. Both ruxolitinib and trametinib significantly reduced basal OCR and ECAR in HSVSMCs from both T2DM and non-diabetic patients. Together, these findings demonstrate a JAK/STAT- and MAPK/ERK-mediated regulation of mitochondrial function in HSVSMCs. As such, they represent potential targets for regulation of HSVSMC function that can be explored for drug development to limit saphenous VGF in T2DM.

Phenotypic switching of vascular smooth muscle cells (VSMCs), leading to neointima formation, is a main cause of in-stent restenosis after coronary stent implantation, resulting in poor patient prognosis. Inhibition of VSMC proliferation, migration, and synthetic phenotype transition holds promise for preventing and treating neointimal hyperplasia and restenosis. GW0742, a peroxisome proliferator-activated receptor (PPAR)-β/δ agonist, has been reported to suppress atherosclerosis and myocardial ischemia-reperfusion injury. However, its role in neointima formation has not been previously studied. In this study, we found that GW0742 significantly inhibited carotid artery injury-induced neointimal hyperplasia in mice. In vitro experiments including cell counting, EdU staining, and proliferation marker detection revealed that GW0742 markedly suppressed Platelet-derived growth factor-BB (PDGF-BB)-induced proliferation of human aortic smooth muscle cells (HASMCs). Flow cytometry analysis showed that GW0742 treatment arrested cells in the G2/M phase. Transwell assays demonstrated that GW0742 inhibited HASMCs migration. Moreover, GW0742 reduced the expression of migration-associated proteins matrix metalloproteinases 2 (MMP2) and matrix metalloproteinases 9 (MMP9), while increasing contractile markers alpha-smooth muscle actin (α-SMA) and calponin 1 (CNN1), suggesting that GW0742 suppresses HASMC proliferation, migration, and phenotypic switching, thereby preserving the contractile phenotype. RNA sequencing revealed that GW0742 regulates fatty acid metabolism by upregulating fatty acid binding protein 3 (FABP3) expression to counteract PDGF-BB-induced VSMC phenotypic switching. Knockdown of FABP3 significantly abrogated the inhibitory effects of GW0742 on VSMC proliferation, migration, and synthetic phenotype transition. Taken together, our findings demonstrate that GW0742 upregulates FABP3 expression, leading to the inhibition of VSMC proliferation, migration, and phenotypic switching, and ultimately suppressing neointima formation. These results underscore the therapeutic potential of GW0742 for the prevention and treatment of vascular restenosis.