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Bone tissue engineering (BTE) has become a hopeful potential treatment strategy for large bone defects, including bone tumors, trauma, and extensive fractures, where the self-healing property of bone cannot repair the defect. Bone tissue engineering is composed of three main elements: progenitor/stem cells, scaffold, and growth factors/biochemical cues. Among the various biomaterial scaffolds, hydrogels are broadly used in bone tissue engineering owing to their biocompatibility, controllable mechanical characteristics, osteoconductive, and osteoinductive properties. During bone tissue engineering, angiogenesis plays a central role in the failure or success of bone reconstruction via discarding wastes and providing oxygen, minerals, nutrients, and growth factors to the injured microenvironment. This review presents an overview of bone tissue engineering and its requirements, hydrogel structure and characterization, the applications of hydrogels in bone regeneration, and the promising roles of hydrogels in bone angiogenesis during bone tissue engineering.

Transient Receptor Potential Vanilloid 4 (TRPV4), a non-selective cation channel in trabecular meshwork (TM) tissue, is activated by forces like deformation and shear stress, playing a critical role in intraocular pressure (IOP) regulation. However, the mechanisms by which TRPV4 mediates TM cells responses to elevated intraocular pressure (IOP), along with the resulting regulatory outcomes, remain incompletely understood. In vitro, TM cells were mechanically stretched, and the effects on TRPV4 activation and calcium influx were evaluated via confocal microscopy, Western blotting, and immunofluorescence. Pharmacological agonists and inhibitors were used to investigate signaling mechanisms. In vivo, ocular hypertension (OHT) was induced in mice, and IOP was measured following drug treatments. Subsequently, IOP was measured after drug administration. Transcriptome sequencing was performed to detect TRPV4 activation-induced alterations in RNA expression and to explore associated regulatory pathways. Mechanical stretch significantly reduced YAP1 mRNA expression in TM cells. TRPV4 activation induced YAP nuclear translocation, which was inhibited by HC067047, confirming TRPV4-YAP signaling. Transcriptome sequencing confirmed that the PI3K/AKT signaling pathway is crucial in mediating YAP activation. In vivo, HC067047 and VP treatment significantly lowered IOP and reduced the accumulation of ECM proteins in TM tissues. Our study demonstrates the critical role of TRPV4-YAP signaling in TM cell function and IOP regulation. These findings indicate that targeting the TRPV4-PI3K/AKT-YAP axis may offer novel therapeutic strategies for glaucoma.​

Coxsackievirus A6 (CVA6), a major cause of hand, foot, and mouth disease, lacks approved vaccines or drugs. KRM1 is its only known receptor, but its precise role remains unclear. This study investigates CVA6’s entry mechanism and antibody neutralization. Cryo-EM shows CVA6 clinical strain HeB primarily exists as mature virions. KRM1 binding within the canyon triggers conversion to uncoating intermediate, defining KRM1 as an uncoating receptor for CVA6. However, KRM1 knockout reduces CVA6 infectivity without affecting attachment. Conversely, disrupting heparan sulfate proteoglycan (HSPG) impairs both viral attachment and infectivity, and CVA6 virions bind heparin directly. These results support a two-receptor entry model for CVA6: HSPG mediates viral attachment, while KRM1 induces uncoating. Additionally, we develop two CVA6-specific protective antibodies (1F4 and 3H7), targeting a new antigenic site near the three-fold axis of the viral capsid. These antibodies sterically block KRM1 binding and function post-attachment, consistent with KRM1’s role. The findings elucidate CVA6 entry and offer a basis for antibody interventions. This study defines a two-receptor entry mechanism for coxsackievirus A6: heparan sulfate for initial attachment and KRM1 for uncoating. Protective antibodies that block KRM1 binding were identified, offering a path for therapeutic development.

There is different administration routes of triamcinolone acetonide (TA) administration for macular edema, but the efficacy ranking remains unclear. The purpose of this study is to assess the efficacy of different administration routes of TA employed in macular edema. PubMed, Medline, Embase, and Cochrane Central Register of Controlled Trials were systematically searched for published articles comparing macular edema in patients with triamcinolone acetonide in different administration. The sparse network was evaluated using a random-effects model and consistency model within the Bayesian framework, utilizing the multinma package in R. The evidence was assessed based on the Grading of Recommendations. Assessment, Development, and Evaluation (GRADE) criteria. A total of 1138 citations were identified by our search, of which 20 RCTs enrolled 892 eyes. The network showed that intravitreal triamcinolone acetonide (IVTA) was associated with a statistically significant better best corrected visual acuity (BCVA) at the 12th week compared to placebo (MD: − 0.15, 95% CI: − 0.30 to − 0.01, P < 0.05), which was moderate-quality evidence. IVTA and suprachoroidal triamcinolone acetonide (SCTA) were both associated with a statistically significant reduction in central macular thickness (CMT) at the 12th week, which was moderate evidence. The probabilities of rankings and SUCRA demonstrated that sub-Tenon’s infusion of triamcinolone acetonide (STiTA) might be the worst. SCTA and IVTA were proven to be the best administration routes for improving BCVA and reducing CMT. In addition, STiTA was less advisable than other administration routes of triamcinolone acetonide according to the rankings and SUCRA.

Background The three-amino-acid-loop-extension ( TALE ) superfamily genes are broadly present in plants and play important roles in plant growth, development, and abiotic stress responses. So far, the TALE family in B.napus have not been systematically studied, especially their potential roles in response to abiotic stress. Results In this study, we identified 74 TALE family genes distributed on 19 chromosomes in the B. napus genome using bioinformatics methods. Phylogenetic analysis divided the BnTALE superfamily into two subfamilies, the BEL1-like (BLH/BELL homeodomain) and the KNOX (KNOTTED-like homeodomain) subfamilies. Moreover, the KNOX subfamily could be further categorized into three clades (KNOX Class I, KNOX Class II, and KNOX Class III). BnTALE members in the same subclass or branch of the phylogenetic tree generally showed similar gene structures and conserved domain compositions, which may indicate that they have similar biological functions. The BnTALE promoter regions contained many hormone-related elements and stress response elements. Duplication events identification analysis showed that WGD/segmental duplications were the main drivers of amplification during the evolution of TALE genes, and most of the duplicated BnTALE genes underwent purifying selection pressures during evolution. Potential protein interaction network analysis showed that a total of 12,615 proteins might interact with TALE proteins in B. napus. RNA-seq and qRT-PCR analyses showed that the expression of BnTALE was tissue-differentiated and can be induced by abiotic stresses such as dehydration, cold, and NaCl stress. In addition, weighted gene co-expression network analysis (WGCNA) identified four co-expression modules containing the most BnTALE genes, which would be notably related to dehydration and cold stresses. Conclusions Our study paves the way for future gene functional research of BnTALE and facilitate their applications in the genetic improvement of B. napus in response to abiotic stresses.

Glaucoma is one of the leading causes of irreversible blindness in developed countries, and intraocular pressure (IOP) is primary and only treatable risk factor, suggesting that to a significant extent, glaucoma is a disease of IOP disorder and pathological mechanotransduction. IOP-lowering ways are limited to decreaseing aqueous humour (AH) production or increasing the uveoscleral outflow pathway. Still, therapeutic approaches have been lacking to control IOP by enhancing the trabecular meshwork (TM) pathway. Trabecular meshwork cells (TMCs) have endothelial and myofibroblast properties and are responsible for the renewal of the extracellular matrix (ECM). Mechanosensitive cation channels, including Piezo1 and TRPV4, are abundantly expressed in primary TMCs and trigger mechanostress-dependent ECM and cytoskeletal remodelling. However, prolonged mechanical stimulation severely affects cellular biosynthesis through TMC mechanotransduction, including signaling, gene expression, ECM remodelling, and cytoskeletal structural changes, involving outflow facilities and elevating IOP. As for the functional coupling relationship between Piezo1 and TRPV4 channels, inspired by VECs and osteoblasts, we hypothesized that Piezo1 may also act upstream of TRPV4 in glaucomatous TM tissue, mediating the activation of TRPV4 via Ca 2+ inflow or Ca 2+ binding to phospholipase A2(PLA2), and thus be involved in increasing TM outflow resistance and elevated IOP. Therefore, this review aims to help identify new potential targets for IOP stabilization in ocular hypertension and primary open-angle glaucoma by understanding the mechanical transduction mechanisms associated with the development of glaucoma and may provide ideas into novel treatments for preventing the progression of glaucoma by targeting mechanotransduction.

Currently, complex scene classification strategies are limited to high-definition image scene sets, and low-quality scene sets are overlooked. Although a few studies have focused on artificially noisy images or specific image sets, none have involved actual low-resolution scene images. Therefore, designing classification models around practicality is of paramount importance. To solve the above problems, this paper proposes a two-stage classification optimization algorithm model based on MPSO, thus achieving high-precision classification of low-quality scene images. Firstly, to verify the rationality of the proposed model, three groups of internationally recognized scene datasets were used to conduct comparative experiments with the proposed model and 21 existing methods. It was found that the proposed model performs better, especially in the 15-scene dataset, with 1.54% higher accuracy than the best existing method ResNet-ELM. Secondly, to prove the necessity of the pre-reconstruction stage of the proposed model, the same classification architecture was used to conduct comparative experiments between the proposed reconstruction method and six existing preprocessing methods on the seven self-built low-quality news scene frames. The results show that the proposed model has a higher improvement rate for outdoor scenes. Finally, to test the application potential of the proposed model in outdoor environments, an adaptive test experiment was conducted on the two self-built scene sets affected by lighting and weather. The results indicate that the proposed model is suitable for weather-affected scene classification, with an average accuracy improvement of 1.42%.

UFMylation, similar to ubiquitination, is a unique post-translational modification which is indispensable in hematopoiesis, neurogenesis and chondrogenesis. However, its role in intervertebral disc development remains unclear. In this study, we focused on DDRGK domain containing protein 1 (DDRGK1), a pivotal component involved in UFMylation, and generated Ddrgk1 fl/fl ; Acan-CreER T2 ( Ddrgk1 cKO ) mice to explore DDRGK1’s regulatory function in the nucleus pulposus and cartilage endplate. We found that Ddrgk1 conditional knockout led to severe retardation of spinal growth, disruption of disc cellularity and initiation of disc degeneration during early postnatal phase. Furthermore, Ddrgk1 conditional knockout in late postnatal phase resulted in profound degeneration of mouse discs, mainly characterized by substantially reduced thickness of cartilage endplate. In addition, Ddrgk1 cKO mice exhibited exacerbated disc degeneration compared to the WT mice after the lumbar spine instability surgery. RNA sequencing of disc cells from Ddrgk1 cKO mice showed upregulation of genes related to apoptosis, matrix metalloproteinase activation, extracellular matrix (ECM) degradation and endoplasmic reticulum (ER) unfolded protein response after Ddrgk1 conditional knockout. Immunohistochemical analysis further verified increased apoptosis, ECM disruption and ER stress in both nucleus pulposus and cartilage endplate after Ddrgk1 conditional knockout. In summary, this study demonstrated that DDRGK1 preserves the normal cellularity and structure of intervertebral discs by regulating the cell fate of nucleus pulposus and cartilage endplate cells, maintaining the ER homeostasis and regulating the metabolic balance of ECM.

Soil visible and near–infrared reflectance spectroscopy is an effective tool for the rapid estimation of soil organic carbon (SOC). The development of spectroscopic technology has increased the application of spectral libraries for SOC research. However, the direct application of spectral libraries for SOC prediction remains challenging due to the high variability in soil types and soil–forming factors. This study aims to address this challenge by improving SOC prediction accuracy through spectral classification. We utilized the European Land Use and Cover Area frame Survey (LUCAS) large–scale spectral library and employed a geographically weighted principal component analysis (GWPCA) combined with a fuzzy c–means (FCM) clustering algorithm to classify the spectra. Subsequently, we used partial least squares regression (PLSR) and the Cubist model for SOC prediction. Additionally, we classified the soil data by land cover types and compared the classification prediction results with those obtained from spectral classification. The results showed that (1) the GWPCA–FCM–Cubist model yielded the best predictions, with an average accuracy of R2 = 0.83 and RPIQ = 2.95, representing improvements of 10.33% and 18.00% in R2 and RPIQ, respectively, compared to unclassified full sample modeling. (2) The accuracy of spectral classification modeling based on GWPCA–FCM was significantly superior to that of land cover type classification modeling. Specifically, there was a 7.64% and 14.22% improvement in R2 and RPIQ, respectively, under PLSR, and a 13.36% and 29.10% improvement in R2 and RPIQ, respectively, under Cubist. (3) Overall, the prediction accuracy of Cubist models was better than that of PLSR models. These findings indicate that the application of GWPCA and FCM clustering in conjunction with the Cubist modeling technique can significantly enhance the prediction accuracy of SOC from large–scale spectral libraries.