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Epigenetic regulations play crucial roles in leukemogenesis and leukemia progression. SUV39H1 is the dominant H3K9 methyltransferase in the hematopoietic system, and its expression declines with aging. However, the role of SUV39H1 via its-mediated repressive modification H3K9me3 in leukemogenesis/leukemia progression remains to be explored. We found that SUV39H1 was down-regulated in a variety of leukemias, including MLL-r AML, as compared with normal individuals. Decreased levels of Suv39h1 expression and genomic H3K9me3 occupancy were observed in LSCs from MLL-r-induced AML mouse models in comparison with that of hematopoietic stem/progenitor cells. Suv39h1 overexpression increased leukemia latency and decreased the frequency of LSCs in MLL-r AML mouse models, while Suv39h1 knockdown accelerated disease progression with increased number of LSCs. Increased Suv39h1 expression led to the inactivation of Hoxb13 and Six1, as well as reversion of Hoxa9/Meis1 downstream target genes, which in turn decelerated leukemia progression. Interestingly, Hoxb13 expression is up-regulated in MLL-AF9-induced AML cells, while knockdown of Hoxb13 in MLL-AF9 leukemic cells significantly prolonged the survival of leukemic mice with reduced LSC frequencies. Our data revealed that SUV39H1 functions as a tumor suppressor in MLL-AF9-induced AML progression. These findings provide the direct link of SUV39H1 to AML development and progression.

Background Hair follicles (HFs) are dynamic structures which are readily accessible within the skin that contain various pools of stem cells with broad regenerative potential, such as dermal papilla cells (DPCs), dermal sheath cells, and epithelial HF stem cells. DPCs act as signalling centres for HF regeneration. The current method for isolating human DPCs are inefficient. These methods struggle to obtain freshly isolated original DPCs and do not maintain the characteristics of DPCs effectively. Methods In this study, two simple but more efficient methods were explored. Force-triggered density gradient sedimentation (FDGS) and cocktail enzyme digestion treatment (CEDT) were used to isolate purified DP spheres from human HFs, obtaining purified freshly isolated original DPCs from DP spheres. The expression profiles of isolated DPCs were tested, and gene expression of DPC-specific markers were analyzed using immunofluorescence staining, RT-qPCR and western blot. Results The 10% Ficoll PM400 was determined as the optimal concentration for FDGS method. Primary DPCs, DSCs and HFSCs were isolated simultaneously using the FDGS and CEDT method. The expression profiles of fresh DPCs isolated using the FDGS and CEDT methods were similar to those of traditionally isolated DPCs. DP-specific markers were expressed at significantly higher levels in freshly isolated DPCs than in traditionally isolated DPCs. Conclusions Compared to traditional methods, the presented laboratory protocols were able to isolate fresh DPCs with high efficiency, thereby improving their research potential.

Hair follicle (HF) regeneration technology holds promise for treating hair loss, but creating a biomimetic structure that mimics the natural follicle microenvironment remains challenging. Here a novel bioengineered hair germ (BHG) is developed using thermodynamically incompatible mucopolysaccharides to enhance HF regeneration efficiency. Mucopolysaccharide‐based hydrogels are synthesized by grafting amino and diethylamino groups (dihydroxyphenylalanine‐grafted hyaluronic acid (HME) hydrogels) for rapid gelation and strong wetting adhesion. Dual‐layered microspheres are fabricated using a co‐flow microfluidic system, with HME as the outer shell and gelatin methacrylate (GelMA) as the core, achieving thermodynamic incompatibility. The Wnt3a protein is encapsulated for sustained release. RNA sequencing, reverse transcription quantitative polymerase chain reaction (RT‐qPCR), and functional validation are used to study the molecular mechanisms of HF regeneration. Results show that HME hydrogels exhibit excellent adhesion, shear‐thinning behavior, and biocompatibility. The microspheres release Wnt3a for up to 9 days, with high‐throughput sequencing revealing upregulation of HF regeneration genes like Ctnnb1 and Lef1, and activation of the Wnt signaling pathway, while hypoxia‐related genes such as Hif‐1ɑ are downregulated. Pathway enrichment analyses confirm the enrichment of HF regeneration pathways. In conclusion, the HME‐based BHG microspheres effectively promote in vivo HF regeneration, offering a promising solution for hair loss treatment and regeneration. Here, a novel bioengineered hair germ (BHG) system is developed using thermodynamically incompatible mucopolysaccharides for efficient hair follicle regeneration. The BHG microspheres, produced via microfluidic technology, encapsulate Wnt3a for sustained release, enhancing mesenchymal stem cell differentiation and activating key regeneration pathways. In vivo experiments confirm the system's potential for scalable hair regeneration, offering a promising treatment for hair loss.

Molecular genetic changes in acute myeloid leukemia (AML) play crucial roles in leukemogenesis, including recurrent chromosome translocations, epigenetic/spliceosome mutations and transcription factor aberrations. Six1, a transcription factor of the Sine oculis homeobox (Six) family, has been shown to transform normal hematopoietic progenitors into leukemia in cooperation with Eya. However, the specific role and the underlying mechanism of Six1 in leukemia maintenance remain unexplored. Here, we showed increased expression of SIX1 in AML patients and murine leukemia stem cells (c‐Kit+ cells, LSCs). Importantly, we also observed that a higher level of Six1 in human patients predicts a worse prognosis. Notably, knockdown of Six1 significantly prolonged the survival of MLL‐AF9‐induced AML mice with reduced peripheral infiltration and tumor burden. AML cells from Six1‐knockdown (KD) mice displayed a significantly decreased number and function of LSC, as assessed by the immunophenotype, colony‐forming ability and limiting dilution assay. Further analysis revealed the augmented apoptosis of LSC and decreased expression of glycolytic genes in Six1 KD mice. Overall, our data showed that Six1 is essential for the progression of MLL‐AF9‐induced AML via maintaining the pool of LSC. In this study, we found that Six1 is a key transcription factor that is differentially expressed in normal hematopoiesis and leukemogenesis and regulates LSC pools by modulating the expression of glycolytic genes.

To precisely delineate the contours of insulators in complex transmission line images obtained from Unmanned Aerial Vehicle (UAV) inspections and thereby facilitate subsequent defect analysis, this study proposes an instance segmentation framework predicated upon an enhanced SOLOv2 model. The proposed framework integrates a preprocessed edge channel, generated through the Non-Subsampled Contourlet Transform (NSCT), which augments the model’s capability to accurately capture the edges of insulators. Moreover, the input image resolution to the network is heightened to 1200 × 1600, permitting more detailed extraction of edges. Rather than the original ResNet + FPN architecture, the improved HRNet is utilized as the backbone to effectively harness multi-scale feature information, thereby enhancing the model’s overall efficacy. In response to the increased input size, there is a reduction in the network’s channel count, concurrent with an increase in the number of layers, ensuring an adequate receptive field without substantially escalating network parameters. Additionally, a Convolutional Block Attention Module (CBAM) is incorporated to refine mask quality and augment object detection precision. Furthermore, to bolster the model’s robustness and minimize annotation demands, a virtual dataset is crafted utilizing the fourth-generation Unreal Engine (UE4). Empirical results reveal that the proposed framework exhibits superior performance, with AP0.50 (90.21%), AP0.75 (83.34%), and AP[0.50:0.95] (67.26%) on a test set consisting of images supplied by the power grid. This framework surpasses existing methodologies and contributes significantly to the advancement of intelligent transmission line inspection.

Inonotus obliquus (Chaga mushroom) is a kind of medicine and health food widely used by folk in China, Russia, Korea, and some occidental countries. Among the extracts from Inonotus obliquus, Inonotus obliquus polysaccharide (IOPS) is supposed to be one of the major bioactive components in Inonotus obliquus, which possesses antitumor, antioxidant, anti-virus, hypoglycemic, and hypolipidemic activities. In this review, the current advancements on extraction, purification, structural characteristics, and biological activities of IOPS were summarized. This review can provide significant insight into the IOPS bioactivities as their in vitro and in vivo data were summarized, and some possible mechanisms were listed. Furthermore, applications of IOPS were reviewed and discussed; IOPS might be a potential candidate for the treatment of cancers and type 2 diabetes. Besides, new perspectives for the future work of IOPS were also proposed.

Dexmedetomidine (DEX) is commonly used in clinical practice because of its sedative, analgesic, antisympathetic, hemodynamic stabilization and antianxiety effects. Previous clinical studies have demonstrated that DEX plays a role in both the prevention and treatment of perioperative arrhythmias. However, the precise mechanisms underlying the effects of DEX remain unclear. Furthermore, few studies have examined the effect of DEX on cardiac electrophysiology. ECG recording was performed in vivo and ex vivo on C57 mice. Simultaneous recording of membrane voltage (Vm) and [Ca 2+ ]i changes was achieved with dual-dye optical mapping, in which voltage- and Ca 2+ -sensitive dyes are employed. Simultaneous programmed electrical stimulation was used to pacing and induce arrhythmias. Simulating catecholamine-induced arrhythmias with isoprotereno (ISO) and preconditioning with DEX to investigate the antiarrhythmic effects of DEX. Our findings demonstrated that ISO increased the incidence of ventricular tachycardia or ventricular fibrillation in mice during rapid pacing stimulation. DEX preconditioning reduced the incidence of ISO-induced ventricular arrhythmias. Optical mapping with simultaneous recordings of dual dyes ( Vm dye and intracellular Ca 2+ dye) revealed that DEX pretreatment attenuated the ISO-induced shortening of action potential duration (APD), calcium transient duration (CaTD), and time-to-peak (TTP) of calcium transients, as well as the ISO-induced increase in repolarization heterogeneity. DEX also slowed the conduction velocity. More importantly, DEX preconditioning significantly reduced the calcium transient alternans ratio at 80-ms, 70-ms, and 60-ms pacing cycles. These findings suggest that DEX preconditioning can reduce the incidence of ventricular arrhythmias induced by acute stress simulated by ISO. Prolongation of action potential duration and calcium transient duration and the maintenance of intracellular calcium homeostasis may be the electrophysiological mechanisms involved.

Solid-state quantum emitters are pivotal for modern photonic quantum technology, yet their inherent spectral inhomogeneity imposes a critical challenge in pursuing scalable quantum network. Here, we develop a cryogenic-compatible strain-engineering platform based on a polydimethylsiloxane (PDMS) stamp, which we show can also work properly at cryogenic temperature. In-situ three-dimensional (3D) strain control is achieved for quantum dots (QDs) embedded in photonic nanostructures. The compliant PDMS enables independent tuning of emission energy and strong reduction of fine structure splitting (FSS) of single QDs, as demonstrated by a 7 meV spectral shift with a near-vanishing FSS in circular Bragg resonators and an unprecedented 15 meV tuning range in the micropillar. The PDMS-based 3D strain-engineering platform, compatible with diverse photonic structures at cryogenic temperature, provides a powerful and versatile tool for exploring fundamental strain-related physics and advancing integrated photonic quantum technology. Spectral inhomogeneity of solid-state quantum emitters hinders their application in scalable quantum networks. Here the authors use in-situ 3D strain engineering at cryogenic temperatures to independently tune emission energy and suppress fine structure splitting in quantum dots embedded in photonic structures.

A large number of waste tires are in urgent need of effective treatment, and breaking waste tires into crumb rubber powder for modifying asphalt has been proved as a good idea to solve waste tires. Crumb rubber modified asphalt not only has good high and low temperature performance, durability, and aging resistance but can also reduce pavement noise and diseases, which has wide application prospects. In this study, crumb rubber powder was desulfurized by mechanochemical method to prepare desulfurized crumb rubber modified asphalt. During the desulfurization process of crumb rubber, the effects of desulfurization process variables including desulfurizer type, desulfurizer content, and desulfurization mixing temperature and time were considered, and then the physical properties of modified asphalt were tested. The test results showed that after mixing crumb rubber powder with desulfurizer, the viscosity of crumb rubber powder modified asphalt can be reduced. Moreover, the storage stability of crumb rubber powder modified asphalt could also be improved by mixing crumb rubber with desulfurizer. Based on the physical properties of crumb rubber powder modified asphalt, the desulfurization process of selected organic disulfide (OD) desulfurizer was optimized as follows: the OD desulfurizer content was 3%, the desulfurization mixing temperature was 160 °C, and the mixing time was 30 min. In addition, Fourier infrared spectroscopy analysis was carried out to explore the modification mechanism of desulfurized crumb rubber powder modified asphalt. There is no fracture and formation of chemical bonds, and the modification of asphalt by crumb rubber powder is mainly physical modification.

The purpose of this study is to identify the risk factors of in-hospital mortality in patients with acute coronary syndrome (ACS) and to evaluate the performance of traditional regression and machine learning prediction models. The data of ACS patients who entered the emergency department of Fujian Provincial Hospital from January 1, 2017 to March 31, 2020 for chest pain were retrospectively collected. The study used univariate and multivariate logistic regression analysis to identify risk factors for in-hospital mortality of ACS patients. The traditional regression and machine learning algorithms were used to develop predictive models, and the sensitivity, specificity, and receiver operating characteristic curve were used to evaluate the performance of each model. A total of 6482 ACS patients were included in the study, and the in-hospital mortality rate was 1.88%. Multivariate logistic regression analysis found that age, NSTEMI, Killip III, Killip IV, and levels of D-dimer, cardiac troponin I, CK, N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-density lipoprotein (HDL) cholesterol, and Stains were independent predictors of in-hospital mortality. The study found that the area under the receiver operating characteristic curve of the models developed by logistic regression, gradient boosting decision tree (GBDT), random forest, and support vector machine (SVM) for predicting the risk of in-hospital mortality were 0.884, 0.918, 0.913, and 0.896, respectively. Feature importance evaluation found that NT-proBNP, D-dimer, and Killip were top three variables that contribute the most to the prediction performance of the GBDT model and random forest model. The predictive model developed using logistic regression, GBDT, random forest, and SVM algorithms can be used to predict the risk of in-hospital death of ACS patients. Based on our findings, we recommend that clinicians focus on monitoring the changes of NT-proBNP, D-dimer, Killip, cTnI, and LDH as this may improve the clinical outcomes of ACS patients.