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Alveolar type II (AT2) cells are key effector cells for repairing damaged lungs. Direct differentiation into AT2 cells from bone marrow mesenchymal stem cells (BMSCs) is a promising approach to treating acute lung injury (ALI). The mechanisms of BMSC differentiation into AT2 cells have not been determined. The Sonic Hedgehog (Shh) pathway is involved in regulating multiple differentiation of MSCs. However, the role of the Shh pathway in mediating the differentiation of BMSCs into AT2 cells remains to be explored. The results showed that BMSCs significantly ameliorated lung injury and improved pulmonary function in mice with ALI. These improvements were accompanied by a relatively high proportion of BMSCs differentiate into AT2 cells and an increase in the total number of AT2 cells in the lungs. Lung tissue extracts from mice with ALI (ALITEs) were used to mimic the injured lung microenvironment. The addition of ALITEs significantly improved the differentiation efficiency of BMSCs into AT2 cells along with activation of the Shh pathway. The inhibition of the Shh pathway not only reduced the differentiation rate of BMSCs but also failed to mitigate lung injury and regenerate AT2 cells. The results confirmed that promoting AT2 cell regeneration through the differentiation of BMSCs into AT2 cells is one of the important therapeutic mechanisms for the treatment of ALI with BMSCs. This differentiation process is highly dependent on Shh pathway activation in BMSCs in the injured lung microenvironment. [ABSTRACT FROM AUTHOR]

Coal seam mining causes fracture and movement of overlying strata in goaf, and endangers the safety of surface structures and underground pipelines. Based on the engineering geological conditions of 22,122 working face in Cuncaota No.2 Coal Mine of China Shenhua Shendong Coal Group Co., Ltd. a similar material model test of mining overburden rock was carried out. The subsidence of overburden rock was obtained through the full-section strain data of distributed optical fiber technology, and the characteristics of mining surface subsidence were studied. The Weibull model was used to adjust the mathematical form of the first half of the surface subsidence curve via the MMF function. On this basis, the prediction model of coal seam mining surface subsidence was established, and the parameters of the prediction model of surface subsidence were determined. The test results show that with the advancement of coal seam mining, the fit goodness of the surface subsidence prediction curve based on the MMF optimization model reaches 0.987. Compared with the measured values, the relative error of the surface subsidence prediction model is reduced to less than 10%. The model displays good prediction accuracy. The time required for settlement stability in the prediction model is positively correlated with parameter a and negatively correlated with parameter b. The research results can be further extended to the prediction of overburden "three zones" subsidence, and provide a scientific basis for the evaluation of surface subsidence compression potential in coal mine goaf. [ABSTRACT FROM AUTHOR]

The article focuses on the emergence of Cas13d as a competitive alternative to Cas9 in enhancing precision CAR T therapy for tumor patients. Topics include the development of multiplexed effector guide arrays (MEGA) using CRISPR-Cas13d, which enables precise and reversible modulation of the transcriptome in T cells, addressing challenges such as T cell exhaustion, cytotoxicity, and off-target effects associated with traditional Cas9-based approaches.

Sepsis, a life-threatening condition resulting from a dysregulated response to pathogen infection, poses a significant challenge in clinical management. Here, we report a novel role for the autophagy receptor NCOA4 in the pathogenesis of sepsis. Activated macrophages and monocytes secrete NCOA4, which acts as a mediator of septic death in mice. Mechanistically, lipopolysaccharide, a major component of the outer membrane of Gram-negative bacteria, induces NCOA4 secretion through autophagy-dependent lysosomal exocytosis mediated by ATG5 and MCOLN1. Moreover, bacterial infection with E. coli or S. enterica leads to passive release of NCOA4 during GSDMD-mediated pyroptosis. Upon release, extracellular NCOA4 triggers the activation of the proinflammatory transcription factor NFKB/NF-κB by promoting the degradation of NFKBIA/IκB molecules. This process is dependent on the pattern recognition receptor AGER, rather than TLR4. In vivo studies employing endotoxemia and polymicrobial sepsis mouse models reveal that a monoclonal neutralizing antibody targeting NCOA4 or AGER delays animal death, protects against organ damage, and attenuates systemic inflammation. Furthermore, elevated plasma NCOA4 levels in septic patients, particularly in non-survivors, correlate positively with the sequential organ failure assessment score and concentrations of lactate and proinflammatory mediators, such as TNF, IL1B, IL6, and HMGB1. These findings demonstrate a previously unrecognized role of extracellular NCOA4 in inflammation, suggesting it as a potential therapeutic target for severe infectious diseases. Abbreviation: BMDMs: bone marrow-derived macrophages; BUN: blood urea nitrogen; CLP: cecal ligation and puncture; ELISA: enzyme-linked immunosorbent assay; LPS: lipopolysaccharide; NO: nitric oxide; SOFA: sequential organ failure assessment. [ABSTRACT FROM AUTHOR]

Background and Objectives: Although cranioplasty (CP) is a relatively straightforward surgical procedure, it is associated with a high complication rate. The optimal timing for this surgery remains undetermined. This study aimed to identify the most suitable timing for CP to minimize postoperative complications., Methods: We conducted a retrospective analysis of all CP cases performed in our department from August 2015 to March 2022. Data were gathered through case statistics and categorized based on the occurrence of complications. The collapse ratio was determined using 3-dimensional Slicer software., Results: In our retrospective study of 266 patients, 51 experienced postoperative complications, including hydrocephalus, epidural effusion, subdural hematoma, epilepsy, and subcutaneous infection. Logistic regression analysis identified independent predictors of postcranioplasty complications, and a nomogram was developed. The predictive value of the logistic regression model, collapse ratio, and decompression craniotomy-CP operation interval for post-skull repair complications was assessed using receiver operating characteristic curve analysis. No significant differences were observed in postoperative complications and decompression craniotomy-CP intervals between the groups (P = .07, P > .05). However, significant differences were noted in postoperative collapse ratios and CP complications between the groups (P = .023, P < .05). Logistic regression revealed that the collapse ratio (odds ratio = 1.486; 95% CI: 1.001-2.008; P = .01) and CP operation time (odds ratio = 1.017; 95% CI: 1.008-1.025, P < .001) were independent risk factors for postoperative complications. Receiver operating characteristic curve analysis indicated that the collapse ratio could predict CP postoperative complications, with a cutoff value of 0.274, an area under the curve of 0.621, a sensitivity of 62.75%, and a specificity of 63.26%., Conclusion: The post-skull repair collapse ratio is a significant predictor of postoperative complications. It is advisable to base the timing of surgery on the extent of brain tissue collapse, rather than solely on the duration between cranial decompression and CP., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc on behalf of Congress of Neurological Surgeons.)

Recent studies have indicated that the dual-specificity phosphatases (DUSP) family may play a role in the advancement of pancreatic cancer. Exploring the role of the DUSP family in pancreatic cancer development and discovering novel therapeutic targets are crucial for pancreatic cancer therapy. A critical subset of 20 genes exhibiting differential expression was identified, with particular emphasis on four key genes: DUSP10, PTP4A2, SSH3, and CDKN3 by multivariate Cox proportional hazards analysis. These genes were integral to developing a novel risk model for PC, which has been independently validated as a prognostic factor for patients. To provide help for clinical treatment, we performed tumor immune analysis and predicted potential chemical drugs. Notably, our research unveiled elevated expression levels of SSH3 in human PC cells and tissues. Intriguingly, SSH3 expression correlates with the patient grade, staging, and T stage in PC. Additional studies reveal SSH3's role in enhancing PC cell proliferation and migration, intricately linked to the activation of the Notch signaling pathway. These insights provide a deeper understanding of PC pathophysiology and pave the way for novel therapeutic interventions., Competing Interests: None., (AJCR Copyright © 2024.)

Natural small molecules have demonstrated tremendous potential for the construction of supramolecular chiral nanostructures owing to their unique molecular structures and chirality. In this study, novel CO 2 -responsive supramolecular hydrogels were constructed using a series of rosin-based surfactants (C n MPAN, n = 10, 12, and 14). The macroscopic properties, rheological properties, nanostructures, and intermolecular interactions of the hydrogels were investigated using differential scanning calorimetry, rotational rheometry, cryogenic transmission electron microscopy, and Fourier transform infrared spectroscopy. Interestingly, diverse nanostructures containing helical nanofibers, interwoven nanofibers, and twisted nanoribbons were formed in the hydrogels, which were rarely observed in reported supramolecular hydrogels, and the strength of the hydrogels was significantly enhanced by increasing the C n MPAN concentration and the alkyl chain length. The obtained hydrogels exhibited excellent CO 2 -responsiveness, with no obvious variation in the nanostructures and rheological properties after response to CO 2 /N 2 for five cycles. Taking advantage of the chiral nanostructures of hydrogels, gold nanoparticles (GNPs) were further prepared. The average particle sizes of the resulting GNPs were as low as 2.5 nm, and the GNPs also had a chiral structure. It is worth noting that no additional reductants and UV-light irradiation were used during the reduction process of GNPs. This study emphasizes that the unique molecular structure and chirality of rosin are critical for the preparation of hydrogels with chiral nanostructures. In addition, this study enriches the applications of forest resources.

Multipotent mesenchymal stem cells (MSCs) have high self-renewal and multi-lineage differentiation potentials and low immunogenicity, so they have attracted much attention in the field of regenerative medicine and have a promising clinical application. MSCs originate from the mesoderm and can differentiate not only into osteoblasts, cartilage, adipocytes, and muscle cells but also into ectodermal and endodermal cell lineages across embryonic layers. To design cell therapy for replacement of damaged tissues, it is essential to understand the signaling pathways, which have a major impact on MSC differentiation, as this will help to integrate the signaling inputs to initiate a specific lineage. Hedgehog (Hh) signaling plays a vital role in the development of various tissues and organs in the embryo. As a morphogen, Hh not only regulates the survival and proliferation of tissue progenitor and stem populations but also is a critical moderator of MSC differentiation, involving tri-lineage and across embryonic layer differentiation of MSCs. This review summarizes the role of Hh signaling pathway in the differentiation of MSCs to mesodermal, endodermal, and ectodermal cells., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.