Search

Abstract The cell transition from an inflammatory phase to a subsequent proliferative phase is crucial for wound healing, yet the driving mechanism remains unclear. By profiling lncRNA expression changes during human skin wound healing and screening lncRNA functions, we identify SNHG26 as a pivotal regulator in keratinocyte progenitors underpinning this phase transition. Snhg26-deficient mice exhibit impaired wound repair characterized by delayed re-epithelization accompanied by exacerbated inflammation. Single-cell transcriptome analysis combined with gain-of-function and loss-of-function of SNHG26 in vitro and ex vivo reveals its specific role in facilitating inflammatory-to-proliferative state transition of keratinocyte progenitors. A mechanistic study unravels that SNHG26 interacts with and relocates the transcription factor ILF2 from inflammatory genomic loci, such as JUN, IL6, IL8, and CCL20, to the genomic locus of LAMB3. Collectively, our findings suggest that lncRNAs play cardinal roles in expediting tissue repair and regeneration and may constitute an invaluable reservoir of therapeutic targets in reparative medicine.

Due to the rapid development of the space industry, ever higher demands are being made for the optimization and improvement of spacecraft thermal management systems. Thermal control technology has become one of the key bottlenecks that restrict the level of spacecraft design. In this paper, the thermal management technologies (TMTs) for spacecraft electronics are reviewed according to the different heat transfer processes, including heat acquisition, heat transport, and heat rejection. The researches on efficient heat acquisition include the utilization of high thermal conductance materials, the development of novel package structure based on micro-/nano-electromechanical system (MEMS/NEMS) technologies, and advanced near-junction microfluidic cooling techniques. For the heat transport process, various heat pipes and mechanical pumped fluid loops (MPFLs) are widely implemented to transport heat from heat generation components to the ultimate heat sinks. The heat pipes are divided into two categories based on their structure layout, i.e., separated heat pipes and unseparated heat pipes. The merits and demerits of these heat pipes and MPFLs (including the single-phase MPFL and the two-phase MPFL) are discussed and summarized respectively. In terms of the heat rejection for spacecraft, thermal radiators are normally the sole option due to the unique space environment. To meet the requirements of large heat dissipation power and fluctuated thermal environment, research efforts on the radiators mainly focus on the development of deployable radiators, variable emissivity radiators, and the combination with other techniques. Due to the fluctuated characteristics of the heat power of internal electronics and the outer thermal environment, the phase change materials (PCMs) exhibit great advantages in this scenario and have attracted a lot of research attention. This review aims to serve as a reference guide for the development of thermal management system in the future spacecraft.

Abstract In unmanned retail store, providing smart customer service requires two stages: understanding customer needs, and guiding the customer to the product. In this paper, we propose an end-to-end (Customer-to-Shelf) software service framework for unmanned retail. The framework integrates visual recognition technology to detect retail objects, large language models to analyze customer shopping needs and make proper recommendations. First, deep neural network based image recognition models are studied for implementing effective stock keeping units (SKUs) object recognition on the shelf. Second, a novel method is proposed to fine-tune large language models (LLMs) with limited training dataset. Metaheuristic approaches are used to optimize the mask locations in a low dimensional parameter space, resulting a more efficient parameter updating method for limited downstream data. Third, by facilitating an automatic analysis of customer preferences powered by large language models, we present a smart recommender system based on domain-specific knowledge, which completes the Customer-to-Shelf software service framework. Experimental results show that our proposed fine-tuning method, is more efficient than other state-of-the-art training methods for limited downstream domain dataset. Using fine-tuned large models, we can successfully create a seamless shopping experience for customers by understanding personalized needs and providing shopping advice in the unmanned retail store.

Abstract Background Chemokine (C-C motif) receptor 8 (CCR8) is a chemokine receptor selectively expressed on tumor-infiltrating regulatory T cells (Tregs). Strong immunosuppression mediated by CCR8+ Tregs observed in breast and lung malignancies suggest for their functional significance in cancer therapy. To date, detailed characterization of tumor-infiltrating CCR8+ Tregs cells in colorectal cancer (CRC) is limited. Methods To study the presence and functional involvement of CCR8+ Tregs in CRC, we analyzed the proportions of CCR8-expressing T cells in different T cell subsets in tumor and adjacent normal tissues and peripheral blood mononuclear cells (PBMCs) from CRC patients by Flow cytometry. Also, we compared the distribution of CCR8+ T cells in malignant tissues and peripheral lymphoid organs from a subcutaneous CRC murine model. Bioinformatic analysis was performed to address the significance of CCR8 expression levels in CRC prognosis, immune regulatory gene expression profiles and potential molecular mechanisms associated with CCR8+ Tregs in CRC tumors. Further, we administrated an anti-CCR8 monoclonal antibody to CT26 tumor-bearing mice and examined the antitumor activity of CCR8-targeted therapy both in vivo and in an ex vivo confirmative model. Results Here, we showed that Tregs was predominantly presented in the tumors of CRC patients (13.4 ± 5.8, p

Abstract Thermal conductivity is one of the most significant criterion of three-dimensional carbon fiber-reinforced SiC matrix composites (3D C/SiC). Represent volume element (RVE) models of microscale, void/matrix and mesoscale proposed in this work are used to simulate the thermal conductivity behaviors of the 3D C/SiC composites. An entirely new process is introduced to weave the preform with three-dimensional orthogonal architecture. The 3D steady-state analysis step is created for assessing the thermal conductivity behaviors of the composites by applying periodic temperature boundary conditions. Three RVE models of cuboid, hexagonal and fiber random distribution are respectively developed to comparatively study the influence of fiber package pattern on the thermal conductivities at the microscale. Besides, the effect of void morphology on the thermal conductivity of the matrix is analyzed by the void/matrix models. The prediction results at the mesoscale correspond closely to the experimental values. The effect of the porosities and fiber volume fractions on the thermal conductivities is also taken into consideration. The multi-scale models mentioned in this paper can be used to predict the thermal conductivity behaviors of other composites with complex structures.

Abstract Electron beam irradiation can cause damage to biological and organic samples, as determined via transmission electron microscopy (TEM). Cryo-electron microscopy (cryo-EM) significantly reduces such damage by quickly freezing the environmental water around organic molecules. However, there are multiple hypotheses about the mechanism of cryo-protection in cryo-EM. A lower temperature can cause less molecular dissociation in the first stage, or frozen water can have a “cage” effect by preventing the dissociated fragments from flying away. In this work, we use real-time time-dependent density functional theory molecular dynamics(rt-TDDFT-MD) simulations to study the related dynamics. We use our recently developed natural orbital branching (NOB) algorithm to describe the molecular dissociation process after the molecule is ionized. We find that despite the difference in surrounding water molecules at different temperatures, the initial dissociation process is similar. On the other hand, the dissociated fragments fly away at room temperature, while they remain in the same cage when frozen water is used. Our results provide direct support for the cage effect mechanism.

Abstract Urological malignancy (UM) is among the leading threats to health care worldwide. Recent years have seen much investment in fundamental UM research, including mechanistic investigation, early diagnosis, immunotherapy, and nanomedicine. However, the results are not fully satisfactory. Bioprinted research models (BRMs) with programmed spatial structures and functions can serve as powerful research tools and are likely to disrupt traditional UM research paradigms. Herein, a comprehensive review of BRMs of UM is presented. It begins with a brief introduction and comparison of existing UM research models, emphasizing the advantages of BRMs, such as modeling real tissues and organs. Six kinds of mainstream bioprinting techniques used to fabricate such BRMs are summarized with examples. Thereafter, research advances in the applications of UM BRMs, such as culturing tumor spheroids and organoids, modeling cancer metastasis, mimicking the tumor microenvironment, constructing organ chips for drug screening, and isolating circulating tumor cells, are comprehensively discussed. At the end of this review, current challenges and future development directions of BRMs and UM are highlighted from the perspective of interdisciplinary science.

The nucleate boiling process that occurs on the surface of a microheater immersed in a liquid pool under fast transient heating conditions can be regarded as homogeneous or near-homogeneous nucleation, exhibiting a significant difference when compared to boiling at conventional time scales on large and even micro spatial scales. This paper numerically investigates the boiling process at both small spatial and temporal scale by using a validated model. Results indicate a significant difference between the average microheater temperature and the maximum temperature at the boiling surface, which can reach up to 80 °C within the scope of present study. Consequently, the nucleation temperature, typically determined by the average temperature of the microheater in most references, may not precisely represent the homogeneous (or nearly homogeneous) nucleation temperature. At the initiation of nucleation, the profiles at the boundary of superheated zone are approximately circular in the z-plane and arched in the x-plane, respectively. Meanwhile, the profile of the superheated zone boundary at the onset of nucleation under direct heating mode (DHM) appears approximately trapezoidal, exhibiting a significant difference from that observed under indirect heating mode (IHM). It is also noted that the local temperature distribution in the fluid region can be considerably affected by natural convection, potentially exerting a substantial influence on the bubble dynamic behaviors during the subsequent bubble growing phase. These findings may provide valuable references for future experimental study on the mechanisms involving in microscale boiling heat transfer process under rapid heating conditions.

Abstract Background Spexin, a 14 amino acid peptide, has been reported to regulate obesity and its associated complications. However, little is known about the underlying molecular mechanism. Therefore, this study aimed to investigate the effects of spexin on obesity and explore the detailed molecular mechanisms in vivo and in vitro. Methods Male C57BL/6J mice were fed a high-fat diet (HFD) for 12 weeks to induce obesity, and mice fed a standard fat diet were used as controls. Then, these mice were treated with SPX or Vehicle by intraperitoneal injection for an additional 12 weeks, respectively. The metabolic profile, fat-browning specific markers and mitochondrial contents were detected. In vitro, 3T3-L1 cells were used to investigate the molecular mechanisms. Results After 12 weeks of treatment, SPX significantly decreased body weight, serum lipid levels, and improved insulin sensitivity in HFD-induced obese mice. Moreover, SPX was found to promote oxygen consumption in HFD mice, and it increased mitochondrial content as well as the expression of brown-specific markers in white adipose tissue (WAT) of HFD mice. These results were consistent with the increase in mitochondrial content and the expression of brown-specific markers in 3T3-L1 mature adipocytes. Of note, the spexin-mediated beneficial pro-browning actions were abolished by the JAK2/STAT3 pathway antagonists in mature 3T3-L1 cells. Conclusions These data indicate that spexin ameliorates obesity-induced metabolic disorders by improving WAT browning via activation of the JAK2/STAT3 signaling pathway. Therefore, SPX may serve as a new therapeutic candidate for treating obesity.

The study investigates the influence of ultrasound on the microstructure and properties of AlCoCrFeNi fabricated by laser cladding. The results indicate that the grain size of AlCoCrFeNi prepared by ultrasonic assistance is smaller than that prepared without ultrasound. Moreover, employing ultrasound in the fabrication process of AlCoCrFeNi results in an improvement in its electrochemical corrosion resistance. This enhancement can be attributed to the homogenization of the microstructure and the reduction of microgalvanic couples. The wear resistance of AlCoCrFeNi is enhanced with the increase in ultrasound amplitude. The sample prepared using a 15 μm ultrasonic amplitude demonstrates the lowest friction coefficient of 0.3876 and the minimal wear loss of 40.8 mg. The tensile strength and elongation of AlCoCrFeNi are improved as the ultrasonic amplitude increases. The sample prepared using a 15 μm ultrasonic amplitude demonstrates the highest tensile strength and elongation, measuring 1039 MPa and 16.2%, respectively. The enhancement of mechanical properties can be attributed primarily to the grain refinement and the reduction of as-cast defects.

AIM: To investigate the underlying mechanism of dry environment (autumn dryness) affecting the lacrimal glands in rats. METHODS: Twenty Sprague-Dawley rats were randomly divided into two groups. The rats were fed in specific pathogen free environment as the control group (n=10), and the rats fed in dry environment as the dryness group (n=10). After 24d, lacrimal glands were collected from the rats. The tissues morphology was observed by hematoxylin-eosin (HE) staining. Tandem mass tags (TMT) quantitative proteomics analysis technology was used to screen the differential expressed proteins of lacrimal glands between the two groups, then bioinformatics analysis was performed. Further, the immunohistochemical (IHC) method was used to verify the target proteins. RESULTS: In dryness group, the lacrimal glands lobule atrophied, the glandular cavities enlarged, the sparse nuclear distribution and scattered inflammatory infiltration between the acinus were observed. The proteomics exhibited that a total of 195 up-regulated and 236 down-regulated differential expressed proteins screened from the lacrimal glands of rats. It was indicated that the biological processes (BP) of differential expressed proteins mainly included cell processes and single BP. The cellular compositions of differential expressed proteins mainly located in cells, organelles. The molecular functions of differential expressed proteins mainly included binding, catalytic activity. Moreover, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the differential expressed proteins mainly involved lysosome, complement and coagulation cascade, and ribosome pathway. The IHC result verified that the up-regulated expression proteins of Protein S100A9 (S100A9), Annexin A1 (Anxa1), and Clusterin (Clu) in lacrimal glands of rats in dryness group were higher than control group. CONCLUSION: The up-regulated expression proteins of S100A9, Anxa1, and Clu may be the potential mechanisms of dry eye symptoms caused by dry environment. This study provides clues of dry environments causing eye-related diseases for further studies.

Discontinuous perfobond rib shear (PBL) connectors can be applied to fabricated steel-concrete composite beams. In this paper, six push-out specimens were designed to explore the shear performance of PBL under static and repeated loads. Four specimens were used for static push-out test. The remaining two were used for fatigue push-out test. The static load test mainly considers the influence of concrete at steel plate end and post-cast strip on the shear bearing capacity, initial shear stiffness and load-slip curve of discontinuous PBL shear connectors. On the basis of the test results, the calculating formulas of the shear capacity and shear stiffness of discontinuous PBL connectors considering the influence of end bearing, bond group effect and post-cast strip are proposed. The predicted results of the formula are close to the experiment. From the fatigue test results, it is found that the fatigue performance of above specimens with C50 and UHPC is better than that with studs, but the fatigue resistance of discontinuous PBL connectors with UHPC is not increased in proportion to the shear capacity. In addition, the residual slip and shear stiffness of PBL specimens after cyclic loading are related to fatigue load amplitude.

Abstract The left atrial appendage (LAA) occluder is an important medical device for closing the LAA and preventing stroke. The device‐related thrombus (DRT) prevents the implantation of the occluder in exerting the desired therapeutic effect, which is primarily caused by the delayed endothelialization of the occluder. Functional coatings are an effective strategy for accelerating the endothelialization of occluders. However, the occluder surface area is particularly large and structurally complex, and the device is subjected to a large shear friction in the sheath during implantation, which poses a significant challenge to the coating. Herein, a hydrogel coating by the in situ UV‐triggered polymerization of double‐network polyelectrolytes is reported. The findings reveal that the double network and electrostatic interactions between the networks resulted in excellent mechanical properties of the hydrogel coating. The sulfonate and Arg‐Gly‐Asp (RGD) groups in the coating promoted hemocompatibility and endothelial growth of the occluder, respectively. The coating significantly accelerated the endothelialization of the LAA occluder in a canine model is further demonstrated. This study has potential clinical benefits in reducing both the incidence of DRT and the postoperative anticoagulant course for LAA closure.

In response to the challenge of mitigating flight delays, this study introduces an innovative solution that encompasses the prediction of delay durations for existing flights and the subsequent optimization of ground service processes based on these predictions. The indirect forecasting of flight delays is achieved through the construction of a random forest model, exhibiting a remarkable 100% accuracy when considering a 15-minute standard for flight delays. In light of the delay prediction outcomes, distinct delay coefficients are assigned to individual flights, facilitating the development of a ground service optimization model through the application of a genetic algorithm. Within the genetic algorithm optimization framework, significant enhancements have been implemented in the gene encoding of the initial population, incorporating a segmented encoding approach. Employing this refined model to optimize the service sequence and duration of ground service vehicles for all flights culminates in the notable accomplishment of achieving zero delays for the entire set of flights.

Abstract Background Chronic postsurgical pain (CPP) markedly impairs patients’ quality of life. Research has shown that chronic stress may extend incisional nociception in male mice. Dopaminergic (DAergic) neurons in the ventral tegmental area (VTA) are integral to stress-related mental disorders (including major depressive disorder, anxiety disorders, and PTSD) and pain. However, the impact of chronic social defeat stress (CSDS) on mesolimbic dopamine (DA) transmission in the development of CPP is yet to be established. It remains uncertain whether the dopamine signals in the rostral anterior cingulate cortex (rACC), which regulate pain, derive from the VTA. This study aims to explore the role of VTA-rACC dopaminergic circuits in a mouse model of CPP induced by CSDS. Methods We conducted CSDS on C57BL/6 J wild-type male mice (n = 12–16 mice/group) and DAT-cre male mice (n = 10–12 mice/group). After 10 days of CSDS, a left posterior plantar incision was made to establish a mouse model of CPP. Paw withdrawal thresholds (PWTs) were evaluated using Von-Frey fibre stimulation. The open field test (OFT) and elevated plus maze test (EPM) were used to assess pain-related negative emotions. We used immunofluorescence staining and Western Blot to analyse D1, D2, c-Fos, and TH expression. DAergic fibre projections in the VTA-rACC neural pathway were traced using retrograde tracing and immunofluorescence staining. Optogenetics and Chemogenetics were employed to manipulate DAergic neurons in the VTA and their axons in the rACC. Results The ipsilateral PWTs in male C57BL/6 J mice significantly decreased after surgery, returning to baseline after seven days. Conversely, in CSDS mice, ipsilateral PWTs remained reduced for at least 30 days post-incision. A significant reduction in TH-positive neurons expressing c-Fos in the VTA of CPP mice was observed 15 days post-incision. Activating DAergic neurons significantly improved ipsilateral PWTs and locomotor performance in the OFT and EPM in CPP mice post-incision. Additionally, D1 expression in the rACC was found to decrease in CPP mice, and this reduction counteracted the increase in PWTs caused by activating DAergic neuron axon terminals in the rACC. Conclusion CSDS results in chronicity of postsurgical nociception and anxiety-like negative emotions, with alterations in DA transmission playing a role in CPP. Specific activation of DAergic neurons mitigates nociceptive responses and anxiety-like bahaviors, possibly mediated by D1 receptors in the rACC.

Introduction:Dental pulp stem cells from humans possess self-renewal and versatile differentiation abilities. These cells, known as DPSC, are promising for tissue engineering due to their outstanding biological characteristics and ease of access without significant donor site trauma. Existing methods for isolating DPSC mainly include enzyme digestion and explant techniques. Compared with the enzymatic digestion technique, the outgrowth method is less prone to cell damage and loss during the operation, which is essential for DPSC with fewer tissue sources.Methods:In order to maximize the amount of stem cells harvested while reducing the cost of DPSC culture, the feasibility of the optimized explant technique was evaluated in this experiment. Cell morphology, minimum cell emergence time, the total amount of cells harvested, cell survival, and proliferative and differentiation capacity of DPSC obtained with different numbers of explant attachments (A1-A5) were evaluated.Results:There was a reduction in the survival rate of the cells in groups A2-A5, and the amount of harvested DPSC decreased in A3-A5 groups, but the DPSC harvested in groups A1-A4 had similar proliferative and differentiation abilities. However, starting from group A5, the survival rate, proliferation and differentiation ability of DPSC decreased significantly, and the adipogenic trend of the cells became more apparent, indicating that the cells had begun to enter the senescence state.Discussion:The results of our study demonstrated that the DPSC obtained by the optimized explant method up to 4 times had reliable biological properties and is available for tissue engineering.

Intravesical infusion of chemotherapeutics is highly recommended by several clinical guidelines for treating nonmuscle invasive bladder cancer (NMIBC). However, cytotoxic chemotherapeutics can cause a series of side effects, which greatly limits their application. Herein, a starvation therapy strategy was proposed, and elafibranor (ELA) was validated as a safe chemotherapeutic for NMIBC. The results showed that 20 μM ELA was sufficient to inhibit the proliferation and migration of bladder cancer cells and increase the level of intracellular reactive oxygen species (ROS). Furthermore, 2 mg/kg ELA treatment blocked the growth of primary tumors in an immunodeficient model by inhibiting proliferation and inducing apoptosis and improved the survival time of immunocompetent model mice. ELA treatment up to 10 mg/kg met the general safety requirements. We also established a patient-derived conditional reprogramming cell (CRC) model to assess the clinical translational potential of ELA. The antitumor effect and antitumor specificity of ELA treatment were confirmed. This work not only identified a promising chemotherapeutic for NMIBC but also provided a potential methodological system for drug discovery.

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a newly defined refractory adult-onset autoinflammatory syndrome caused by somatic mutations in the ubiquitin-like modifier-activating enzyme 1 (UBA1) gene in hematopoietic stem and progenitor cells, resulting in a shift in UBA1 isoform expression. Thus, patients develop a spectrum of systemic inflammatory manifestations and hematologic symptoms. To date, patients respond poorly to immune suppressive drugs, except high-dose glucocorticoids, and no treatment guidelines have been established. Given the high mortality rate, VEXAS syndrome needs to be taken seriously by physicians in all specialties. This article aims to describe the key features, pathogenesis, and clinical manifestations of VEXAS syndrome to better understand the targeted treatment and improve the prognosis of VEXAS syndrome.