Search Results (505)

A recent publication proposed that the main biological function of chromosomal toxin–antitoxin systems (TASs) in free-living bacteria is to optimize fitness by mediating K Sensing and Control via a Nutrient-Responsive Cybernetic System. Viable cell density data were consistent with analog (continuous) regulation of population dynamics and cellular physiology throughout the life cycle; however, exactly how bacteria utilize TASs to regulate this was not explained in that publication. Two different concepts of injury have been proposed in the field of microbiology: (1) injury due to external physical and chemical stresses, which lead to sublethal (reversible) or lethal (irreversible) injury depending on the degree of injury, and (2) injury due to internal, self-inflicted stresses mediated by TA toxins. While self-inflicted injury due to TA toxins has been recognized as playing a role in growth arrest and dormancy, which can be reversed by repair, there is little support for TA toxins causing irreversible programmed cell death under normal physiological conditions. The purpose of the present paper was to explain how merging the above two concepts of injury might reveal how TASs optimize the fitness of free-living bacteria under normal physiological conditions by continuously regulating the ratio of injury: repair throughout the life cycle. Full article

Background/Objectives: Photobiomodulation (PBMT) has been shown to improve tissue healing; however, the best protocol for different clinical challenges is not clearly determined. Despite the good previous outcomes of the PBMT in healing of the third molar surgical sites, the ideal protocol of PBMT was not determined. The objective of this split-mouth double-blinded randomized clinical trial was to compare the effect of photobiomodulation (PBMT) with red and infrared wavelengths combined and PBMT with only red wavelength on the healing of post-extraction alveoli of third molars. Methods: Twenty patients underwent third molar extraction. The alveoli were treated randomly in a split mouth model with: PBMT with red laser (R-PBMT) or PBMT with red and infrared laser combined (IR-R-PBMT). PBMT was applied immediately, and 3 and 7 days after surgery. Patients were clinically evaluated in relation to repair (bleeding, exudate, color, and consistency of the tissues), degree of the edema, and through the application of a VAS scale (pain, edema, bleeding, chewing, and mouth opening) in the baseline period, and 3, 7, 14, 30, and 90 days after the surgical procedure. In addition, bone tissue density and structure were measured by radiographic analysis at 7 and 90 days postoperatively. Results: Clinical analysis showed that IR-R-PBMT induce more reduction in the edema 7 days after surgery compared with the R-PBMT; however, no significant differences were noted between groups in other parameters. Conclusions: IR-R-PBMT reduces the edema after 7 days of third molar extraction compared with the R-PBMT. Registration: This study was registered with the Brazilian Registry of Clinical Trials (REBEC-RBR-103g7j28; date of registration 12 July 2023) under number U1111-1297-6962. Full article

Neural progenitor cell (NPC) transplantation is a promising strategy for spinal cord injury repair, as graft-derived neurons can integrate into host circuitry and promote functional recovery. While the brain-regional and dorsoventral identities of NPCs are known to influence graft composition and performance, the importance of axial (rostrocaudal) identity, specifically whether NPCs must be matched to the spinal level of injury, remains poorly understood. To address this, we compared outcomes following transplantation of NPCs isolated from the anterior embryonic spinal cord (A-NPCs) versus the posterior spinal cord (P-NPCs) in a mouse model of C5 cervical dorsal column injury. Following transplantation, NPCs retained their intrinsic molecular axial identities; P-NPC grafts maintained significantly higher expression of the lumbar-associated gene HoxC10 and possessed a higher proportion of Chx10-high V2a neurons compared to A-NPCs. Despite these maintained molecular differences, A-NPC and P-NPC grafts were indistinguishable in neuronal and glial density, axon outgrowth, and their ability to support host axon regeneration, including the corticospinal tract. Long-term behavioral testing and retrograde transsynaptic tracing revealed no significant differences between groups in the recovery of skilled pellet reaching, grip strength, or synaptic integration with host cervical motor circuitry. These findings demonstrate that although transplanted NPCs retain their molecular axial identity in the adult injured environment, this identity is not a primary determinant of anatomical integration or functional outcome. Our findings suggest a degree of plasticity in graft-host interactions and indicate that strict segment-matching is not essential for the efficacy of NPC-based therapies in spinal cord injury. Full article

Background: The heterogeneous nature of cancer with varying degrees of fat, necrosis, fibrosis, and varying degrees of tissue repair severely impacts the success of acquiring adequate tissue samples during percutaneous image-guided biopsy. Although ultrasound or CT fluoroscopy are used to identify tumor location and thus to guide biopsy needle insertion, these technologies do not provide the necessary resolution to determine tissue composition and enable the selection of the most appropriate location for biopsy specimen extraction. As a result, biopsy must be repeated, leading to significant cost to the health care system. Methods: In this study, we introduce a combined optical imaging/artificial intelligence (OI/AI) methodology for the real-time assessment of tissue morphology at the tip of the biopsy needle, prior to the collection of a biopsy specimen. Addressing a significant clinical challenge, this approach aims to reduce the proportion of biopsy cores—currently as high as 40%—that yield low diagnostic value due to elevated adipose or low tumor content. Our methodology employs micron-scale optical coherence tomography (OCT) imaging to obtain detailed structural tissue information using a minimally invasive needle probe. The OCT images are automatically analyzed using a convolutional neural network (CNN)-driven AI software developed by our team. A U-net style architecture was used to segment regions of tumor from the OCT scans. U-Net is a specialized convolutional neural network (CNN) architecture designed for fast, precise image segmentation, which involves classifying each pixel in an image to outline objects. This streamlined approach shows promise to provide clinicians with real-time results, supporting more accurate and informed decisions regarding biopsy site selection. To evaluate this technology, we conducted a clinical study using a custom-made OCT imager and recorded OCT images from patients diagnosed with liver cancers. Expert OCT interpreters supplied annotated reference images that were used to train a custom AI algorithm. Results: OCT imaging with ~10 mm axial and 20 mm lateral resolution enabled the collection of high-quality images of the tissue. The AI analysis was performed offline. UNet achieved an AUC of ~0.877 on the validation dataset, indicating promising performance for the relatively small data set used to train the model. The AI model matched human interpretations approximately 90% of the time, highlighting its promise for making biopsy procedures both more accurate and more efficient. Conclusions: A novel OCT instrument and AI software were evaluated for assessing tissue composition at the tip of biopsy needle. The OCT instrument produced micron-scale resolution images of the tissue, enabling AI analysis and accurate real-time discrimination of tissue type. This preliminary study demonstrated the clinical potential of this technology for improving biopsy success. Full article

Background/Objectives: High-voltage, low-current electric shocks inflict superficial second-degree burns on the skin, accompanied by a vicious cycle of excessive oxidative stress and inflammation. As efficient treatment of such electrical burns remains a clinical challenge, we explored the efficacy of an injectable thermosensitive chitosan hydrogel engineered with an antioxidant agent (astaxanthin) and an anti-inflammatory agent (ibuprofen) for the treatment of high-voltage, low-current electrical burn injuries. Methods: The proposed CS/AST/IBU hydrogel was prepared and its thermosensitivity was characterized. Subsequently, the hydrogel was injected into the wounds of male Sprague–Dawley (SD) rats subjected to electrical burn injury (20 kV, 3 mA). Finally, a series of experiments were performed to elucidate the dynamics of wound healing and the mechanisms by which the hydrogel promotes wound repair. Results: The injectable hydrogel, through its thermally responsive gelation effect at 37 °C, adapts to the complex irregularities of the wound surface. This facilitates the release of astaxanthin and ibuprofen throughout the wound, which collectively diminish the formation of reactive oxygen species and MDA. Furthermore, it enhances the synthesis of endogenous antioxidants such as SOD, CAT, and GSH; encourages collagen deposition; stimulates the development of dermal appendages; and fosters neovascularization. It interrupts the deleterious cycle of oxidative stress and inflammation mediated by the NF-κB signaling pathway, thereby suppressing the expression of pro-inflammatory markers such as TNF-α, CD11b, and IL-1β while upregulating CD163, an anti-inflammatory receptor. Conclusions: The use of this multipronged, contour-adaptive hydrogel represents an effective strategy for complex wound management and demonstrates broad therapeutic potential for superficial second-degree electrical burns caused by high-voltage, low-current discharge. Full article

A self-adaptive variant of teaching–learning-based optimization, incorporating a diversity archive and referred to as ATLBO-DA, has been proposed. Combined with a new path repairing technique (PRT), it efficiently accomplishes the four-bar linkage path generation problem, but an upgraded version is needed. An update of ATLBO-DA to self-adaptive teaching–learning-based optimization with evenness factor archive (ATLBO-EFA) and a new path repairing technique are proposed at the present. The diversity archive idea of the original version is replaced with the evenness factor archive to increase the exploitation and exploration performance of the TLBO. An optimum path repairing technique (OPRT) is proposed. This novel approach is used to identify the optimum combination of four-bar mechanism types by employing the concept of Degree of Limiting (DL). Moreover, in this article, a comparative analysis of present update and the previous version use to solve four-bar linkage path generation problems is performed. Several path generation problems are solved using both techniques. The results demonstrate that the updated technique consistently outperforms the earlier version, giving superior values for both mean and minimum descriptive statistics. In addition, the results make it clear that ATLBO-EFA and OPRT are superior to the original version. The result of non-parametric statistic testing using Friedman test indicate that ATLBO-EFA ranks 1st at p-value (0.0455) < α (0.05). It can be concluded that ATLBO-EFA with OPRT offers the best solution for solving the four-bar path synthesis problems. Full article

Although extensive research has been conducted on the regenerants for unmodified and SBS-modified asphalt, in-depth studies on the activation of regenerants to restore the SBS cross-linked network while preserving their diffusion performance have not yet been reported. This study quantitatively evaluated the activation effect of self-healing regenerants on SBS cross-linked networks by testing the activation degree of 6%, 8%, and 10% cross-linked networks with self-healing regenerants; the phase structure of SBS-modified asphalt before and after regeneration was examined using fluorescence microscopy (FM); the underlying mechanism of the reactive regenerant was elucidated by Fourier Transform Infrared Spectroscopy (FTIR) and Gel Permeation Chromatography (GPC); furthermore, the rheological response characteristics of the reactive regenerant and conventional regenerant were comparatively analyzed. The findings indicated that the SBS cross-linked network self-healing regenerant exhibited a more pronounced activation effect on aged asphalt. Specifically, when the dosage of the regenerant reaches 8%, its repairing effect on the cross-linked network becomes particularly significant. Reconstructing the cross-linked network structure of SBS-modified asphalt enabled the recovery of the viscoelastic properties of the recycled asphalt. Nevertheless, an excessive dosage of the regenerant failed to further enhance the cross-linked structure in a meaningful way and might even exert an adverse impact on the high-temperature performance of the recycled asphalt. Full article

Background: Right ventricular outflow tract (RVOT) reconstruction is frequently performed for pediatric patients with pulmonary valve anomalies, yet optimal techniques remain debated. The equine pericardium offers a promising substrate for pulmonary valve reconstruction but has been understudied in pulmonary valve reconstruction. This study evaluated a novel technique using the equine pericardium to create a cylinder bicuspid pulmonary valve for RVOT reconstruction. Methods: In this retrospective cohort study, 17 pediatric patients (median age: 10 months; 53% male) underwent RVOT reconstruction with equine pericardium between 2023 and 2024. The valve was fashioned from a patch of equine pericardium into a cylinder to create a functionally bicuspid valve. The height of the cylinder ranged from 1.5–2 cm. The diameter was measured around a Hegar dilator corresponding to a valve size z-score of +3. The outcomes included the degree of postoperative pulmonary regurgitation, RVOT pressure gradients, postoperative complications, and reinterventions. Results: Postoperatively, the median peak RVOT pressure gradient decreased significantly from 70 mmHg (IQR: 65–90) to 25 mmHg (IQR: 20–40; p < 0.001). Mild pulmonary regurgitation persisted in one patient (5.9%). Five patients had mild right ventricular dysfunction (29.41%). At a median 3-month follow-up (IQR: 1–8), 17.7% (n = 3) underwent cardiac catheterization. There was no postoperative mortality. Conclusions: Cylinder bicuspid pulmonary valve reconstruction using the equine pericardium effectively reduces RVOT obstruction while maintaining pulmonary valve competence and demonstrates acceptable short-term safety. Having a competent pulmonary valve after repairing the hypoplastic pulmonary valve annulus is very promising; however, the small cohort and limited follow-up preclude definitive conclusions about long-term durability. Larger prospective studies with longer follow-up periods are needed to validate this technique for RVOT reconstruction. Full article

Background: Interstitial lung diseases (ILDs) are a heterogeneous group of disorders characterized by variable degrees of inflammation and fibrosis affecting the pulmonary interstitium. Advances in molecular biology and genetics have greatly expanded our understanding of ILD pathogenesis, uncovering novel mechanisms and supporting precision medicine approaches. Genetic Insights: Genetic factors play a pivotal role in ILD heterogeneity, influencing disease onset, severity, and progression. To date, more than 30 genes with different inheritance patterns (autosomal dominant, recessive, or X-linked) have been associated with ILDs. These genes are primarily involved in surfactant metabolism, telomere maintenance, immune regulation, and epithelial repair. Emerging evidence also implicates genes encoding aminoacyl-tRNA synthetases. This review summarizes the main genetic alterations underlying ILD pathogenesis and discusses their impact on diagnostic and therapeutic approaches, highlighting how identification of disease-causing variants can improve diagnostic accuracy, refine prognostic assessment, and inform recurrence risk. Methods: A narrative review was conducted through targeted PubMed and Embase searches using disease- and gene-related keywords. Studies were prioritized based on predefined conceptual criteria, including clinical relevance, strength and replication of genetic associations, and availability of functional or translational evidence. Conclusions: This synthesis brings together the latest genetic insights into pediatric ILDs and their clinical implications. Integrating genomic data into clinical practice may enable earlier diagnosis, tailored follow-up, individualized therapeutic strategies, and more informed genetic counseling. However, important challenges remain, including incomplete genotype–phenotype correlations and limited functional validation for several disease-associated genes, which currently constrain full clinical translation. Full article

The regeneration of bone and the repair of large segmental bone defects represent critical challenges in regenerative medicine. Natural bone tissue is an anisotropic material characterized by an intricate gradient distribution in structure, mechanical properties, and biochemical composition; this multi-dimensional heterogeneity is crucial for maintaining its physiological functions and guiding regeneration. Although tissue engineering scaffolds have demonstrated significant potential in the treatment of bone defects, homogeneous or single-gradient scaffolds often struggle to precisely recapitulate the high degree of heterogeneity and anisotropy of natural bone from the macroscopic to the microscopic level, thereby limiting their capability in repairing complex bone defects. In recent years, biomimetic gradient scaffolds—particularly those employing multi-gradient synergistic designs that integrate physical structure, biochemical composition, and mechanical properties—have emerged as a research frontier in this field due to their ability to accurately mimic the natural bone microenvironment and regulate cellular behavior. This research aims to systematically review the latest research progress in gradient scaffolds for bone tissue engineering. First, gradient characteristics of biomimetic gradient bone scaffolds are summarized; second, the design strategies for gradient scaffolds are discussed in depth, with a focus on the applications and advantages of advanced fabrication techniques, such as additive manufacturing, in constructing multi-dimensional gradient structures; finally, based on current research findings, the emerging development trends and future research directions of biomimetic gradient bone scaffolds are outlined to provide a reference for innovative breakthroughs in the field of bone tissue engineering. Full article

This study systematically investigated the genomic alterations in Saccharomyces cerevisiae driven by Replication Factor A (RFA) dosage insufficiency using a promoter-replacement strategy combined with mutation accumulation and whole-genome sequencing. Our findings reveal that transcriptional suppression of RFA2 or RFA3 leads to severe growth inhibition. RFA deficiency induces a distinct mutational spectrum characterized by a high frequency of monosomy and terminal deletions, indicative of severe replication stress. Furthermore, loss of heterozygosity is significantly enriched at centromeres and high-GC regions, underscoring the role of RFA in stabilizing intrinsic genomic barriers. Utilizing an APOBEC3B-induced mutagenesis assay, we demonstrate that RFA insufficiency leads to the extensive accumulation of exposed ssDNA with a distinct bias towards the lagging strand template. Notably, we observed that cells spontaneously inactivate Mismatch Repair (MMR) genes, such as MSH2 and PMS1, to survive RFA-induced stress. This hypermutant phenotype grants a certain degree of growth recovery on Low Galactose (LG) medium. Overall, these findings demonstrate that RFA dosage is a key determinant of genomic integrity and elucidate how repair pathway modulation drives adaptive evolution under replication stress. Full article

The renovation of dilapidated housing has become a focal point of social concern. However, traditional approaches—such as repair and reinforcement or unified demolition and relocation—face bottlenecks that hinder sustainability. There is an urgent need to explore new models for addressing the risks posed by dilapidated residential buildings. In recent years, multiple regions have explored the “original demolition and original reconstruction” approach for dilapidated housing. For instance, Zhejiang Province introduced the “Resident-led Renewal” model, sparking widespread attention and discussion. This model is characterized by residents serving as the primary investors. However, the manner in which stakeholders—particularly residents—collaborate in governance and interact during the renovation process under this model remains unclear. Using the Zhegong New Village original demolition and reconstruction project as a case study, this paper employs social network analysis to construct relational networks encompassing information, trust, consultation, and support. It quantitatively reveals the characteristics of social networks among stakeholders and their interactive practices within the Resident-led Renewal model. Findings reveal that in this case, “Resident-led Renewal” primarily manifested through residents serving as principal investors and establishing a Self-Driven Renewal Committee to submit the original demolition and reconstruction application on behalf of residents to local authorities. In stakeholder interactions, the government and community neighborhood committees play a coordinating role in the renovation process. However, resident organizations and residents themselves ranked lower in metrics such as reciprocity and degree centrality, indicating their limited influence during the renovation process. To alleviate the pressure of the government’s excessive involvement and enhance resident participation in the “original demolition and original reconstruction” process, efforts should focus on: raising residents’ awareness and capacity for participation; ensuring accessible channels for resident involvement; clarifying the rights and responsibilities of all stakeholders; and establishing a standardized approval process for “original demolition and original reconstruction” projects. This approach would realize a “Resident-led Renewal” model characterized by government guidance and resident participation. Full article

This study investigates the effect of three-dimensional (3D) bioprinted collagen (Col) scaffolds (2% w/v collagen) loaded with autologous bone marrow stromal cells (BMSCs) and enriched with bone morphogenetic protein-2 (BMP-2) and hydroxyapatite-based particles (HAPPs) on bone regeneration in calvarial defects in rabbits. Three implant formulations, Col-(BMP-2) (at a concentration of 80 ng/mL), Col-HAPP (1% w/v) and a mixture of the two—Col-(BMP-2)-HAPP (40 ng/mL final concentration and 0.5% HAPP), were compared with a control group C-Per containing only periosteum to assess the influence of material structure, biochemical signals and cell component on osteogenesis. Histological analysis and quantitative computed tomography (CT) imaging parameters (HU values and residual defect diameter) showed significant differences between the groups, highlighting the role of combined strategies for optimal bone repair. The control group demonstrated the weakest regeneration, expressed by minimal lamellar bone and the largest residual defect. Col-(BMP-2) stimulated moderate osteoinduction with active osteoblasts but without a fully organised lamellar structure. Col-HAΡΡ provided more advanced regeneration, with histologically observed thick osteoid lamellae, early calcification, and structured lamellar architecture, emphasising the osteoconductive role of HAΡΡs. The strongest regeneration was reported with Col-(BMP-2)-HAΡΡ, where the synergy between BMP-2, HAΡΡs and BMSCs resulted in formed osteons, well-developed cancellous bone and minimal residual defects. The established negative correlation between bone density and residual calvarial defects emphasises the relationship between mineralisation and the degree of defect filling. The new data presented demonstrate that the combination of the abovementioned structural, biochemical and cellular factors in 3D bioprinted scaffolds offers a promising strategy for osteoregeneration of complex bone defects. Full article

Fire hazard events for road tunnel has correspondingly increased with battery electric vehicle (BEV) penetration rate rising. Compared with conventional internal combustion engine vehicles (ICEV), the research on damage degree of road tunnels caused by BEV fires is not mature. To this end, the temperature distribution and residual load-bearing capacity of road tunnel were studied considering the difference temperature rise curve of BEV fire and ICEV fire. By using the indirect thermal–mechanical coupling approach, the temperature field obtained from fire simulations was applied to the structural model. The assessment of mechanical properties after high-temperature exposure was conducted using the deflection limit method and concrete plastic damage theory. The results show that different heating curve conditions have significant differences in the temperature field and damage distribution of the tunnel. Although different fire effects cause different degrees of structural damage to the tunnel lining, the overall bearing capacity of the structure still has a certain surplus. The results provide a basis for the formulation of repair schemes and reinforcement measures for tunnel structures to assess the safety and normal operation of tunnel structures. Full article

As vital components of urban rail transit networks, subway stations are widely scattered across diverse urban districts, whose sustainability performance exerts a notable impact on the overall urban ecological and environmental quality. This study constructs a three-dimensional numerical model to conduct a comparative assessment of the seismic behavior of subway stations adopting different bearing systems at beam-column joints. The seismic responses of two typical structural configurations, a traditional rigid-jointed subway station and another equipped with rubber isolation bearings, are examined under a series of ground motions, with due consideration of amplitude scaling effects and material nonlinearity. A comprehensive evaluation is carried out on key performance parameters, including structural acceleration responses, column rotation angles, damage evolution processes, and internal force distributions. Based on this analysis, the research clarifies the sustainability implications by establishing quantitative correlations between seismic response indices (i.e., deformation extent, damage degree, and internal force magnitudes) and post-earthquake outcomes, such as repair complexity, material requirements, carbon emissions, and socioeconomic effects. The results can advance the integrated theory of seismic-resilient and sustainable design for underground infrastructure, providing evidence-based guidance for the optimization of future subway station construction projects. Full article