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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.

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 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 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.

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 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.

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 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.

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.

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.

A novel polysaccharide (WAMPa) was purified from Atractylodis macrocephala Koidz. WAMPa was characterized with molecular weight (MW) distribution, infrared spectrum, monosaccharide composition, methylation and nuclear magnetic resonance spectra. The backbone of WAMPa was → 2)-β-D-Glcp-(1 → interspersed with a small amount of → 5)-α-D-Araf-(1→, and the branches were the terminal α-D-Glcp-(1 → and β-D-Glcp-(1→. The immunomodulatory activities of WAMPa were investigated on two levels experiments including in vitro RAW264.7 cells and in vivo zebrafish. Meanwhile, the immune-mediated antitumor activity was evaluated by the inhibitory effect of the culture medium from WAMPa-treated RAW264.7 cells on human breast cancer cell line MCF-7. Bioactivity assays showed that WAMPa increased mRNA expression levels of TNF-α, IL-6 and iNOS, enhanced the levels of NO, and promoted the phosphorylation of ERK, p38 and JNK. Taken together, these findings revealed that WAMPa exhibited immunomodulatory effects by regulating MAPK signaling pathway. The antitumor experiments showed that WAMPa did not show a significant growth inhibition ratio on MCF-7 cells, but WAMPa-treated RAW264.7 macrophages could significantly inhibit the growth of MCF-7 cells. Thus, the antitumor activity of WAMPa was mediated mainly through the activation of macrophages. These results suggested that WAMPa could be considered as potential immunomodulatory and antitumor supplements.

Kawasaki disease (KD) is a systematic vasculitis that is often complicated by coronary artery lesions and is a leading cause of acquired heart disease in developed countries. Previous studies have suggested that genetic susceptibility, together with an inducing infectious agent, could be involved in KD pathogenesis; however, the precise causative agent of this disease remains unknown. Moreover, there are still debates concerning whether KD is an infectious disease or an autoimmune disease, although many studies have begun to show that various pathogens functioning as critical inducers could activate different kinds of immune cells, consequently leading to the dysfunction of endothelial cells and systematic vasculitis. Here in this review, we attempt to summarize all the available evidence concerning pathogen infections associated with KD pathogenesis. We also discuss the related mechanisms, present a future perspective, and identify the open questions that remain to be investigated, thereby providing a comprehensive description of pathogen infections and their correlations with the host immune system in leading to KD.

Parkinson’s disease (PD) could be viewed as a proteinopathy caused by changes in lipids, whereby modifications in lipid metabolism may lead to protein alterations, such as the accumulation of alpha-synuclein (α-syn), ultimately resulting in neurodegeneration. Although the loss of dopaminergic neurons in the substantia nigra is the major clinical manifestation of PD, the etiology of it is largely unknown. Increasing evidence has highlighted the important role of lipids in the pathophysiology of PD. Sphingosine-1-phosphate (S1P), a signaling lipid, has been suggested to have a potential association with the advancement and worsening of PD. Therefore, better understanding the mechanisms and regulatory proteins is of high interest. Most interestingly, S1P appears to be an important target to offers a new strategy for the diagnosis and treatment of PD. In this review, we first introduce the basic situation of S1P structure, function and regulation, with a special focus on the several pathways. We then briefly describe the regulation of S1P signaling pathway on cells and make a special focused on the cell growth, proliferation and apoptosis, etc. Finally, we discuss the function of S1P as potential therapeutic target to improve the clinical symptoms of PD, and even prevent the progression of the PD. In the context of PD, the functions of S1P modulators have been extensively elucidated. In conclusion, S1P modulators represent a novel and promising therapeutic principle and therapeutic method for PD. However, more research is required before these drugs can be considered as a standard treatment option for PD.

Hypopharyngeal squamous cell carcinoma (HSCC) is a highly aggressive malignancy that constitutes approximately 95% of all hypopharyngeal carcinomas, and it carries a poor prognosis. The primary factor influencing the efficacy of anti-cancer drugs for this type of carcinoma is chemoresistance. Carnitine palmitoyltransferase 1A (CPT1A) has been associated with tumor progression in various cancers, including breast, gastric, lung, and prostate cancer. The inhibition or depletion of CPT1A can lead to apoptosis, curbing cancer cell proliferation and chemoresistance. However, the role of CPT1A in HSCC is not yet fully understood. In this study, we discovered that CPT1A is highly expressed in HSCC and is associated with an advanced T-stage and a poor 5-year survival rate among patients. Furthermore, the overexpression of CPT1A contributes to HSCC chemoresistance. Mechanistically, CPT1A can interact with the autophagy-related protein ATG16L1 and stimulate the succinylation of ATG16L1, which in turn drives autophagosome formation and autophagy. We also found that treatment with 3-methyladenine (3-MA) can reduce cisplatin resistance in HSCC cells that overexpress CPT1A. Our findings also showed that a CPT1A inhibitor significantly enhances cisplatin sensitivity both in vitro and in vivo. This study is the first to suggest that CPT1A has a regulatory role in autophagy and is linked to poor prognosis in HSCC patients. It presents novel insights into the roles of CPT1A in tumorigenesis and proposes that CPT1A could be a potential therapeutic target for HSCC treatment.

Abstract Background Pulmonary hypertension (PH) is a lethal vascular disease with limited therapeutic options. The mechanistic connections between alveolar hypoxia and PH are not well understood. The aim of this study was to investigate the role of mitotic regulator Polo-like kinase 1 (PLK1) in PH development. Methods Mouse lungs along with human pulmonary arterial smooth muscle cells and endothelial cells were used to investigate the effects of hypoxia on PLK1. Hypoxia- or Sugen5416/hypoxia was applied to induce PH in mice. Plk1 heterozygous knockout mice and PLK1 inhibitors (BI 2536 and BI 6727)-treated mice were checked for the significance of PLK1 in the development of PH. Results Hypoxia stimulated PLK1 expression through induction of HIF1α and RELA. Mice with heterozygous deletion of Plk1 were partially resistant to hypoxia-induced PH. PLK1 inhibitors ameliorated PH in mice. Conclusions Augmented PLK1 is essential for the development of PH and is a druggable target for PH.

Abstract Background Various data have been obtained on the relationship between body mass index (BMI) and C-reactive protein (CRP) and periodontitis. The aim of this study was to determine whether CRP/BMI are associated with periodontitis using data from the National Health and Nutrition Examination Survey (NHANES) database. Methods A cross-sectional analysis of data from 3602 participants in the 2009–2010 NHANES cycle was performed. The definition of periodontitis was used to divide participants into four groups according to the criteria of Eke. Correlations between CRP/BMI and periodontitis were tested for statistical significance by means of descriptive statistics, multivariate regression, and subgroup-stratified analyses, with and without adjustments for confounders (such as age and sex). Results There were no statistically significant differences (p > 0.05) regarding BMI and the development of periodontitis. After adjustment for age, sex, race, marital status, annual family income, alcohol consumption, hypertension, smoking, chronic pulmonary disease, cardiovascular disease, diabetes, flossing, and arthritis, CRP correlated significantly with the development of periodontitis in the subgroups stratified by obesity, with an odds ratio (OR) of 1.2 (95% CI, 1.0 to 1.5). Conclusion Through data analysis, we found an association between CRP levels and periodontitis prevalence in the American population, although this association was only present in the obese population. While there are several hypotheses about the underlying mechanism, further studies are needed to validate these findings.

Abstract Background The dried bark of Ailanthus altissima (Mill.) Swingle is widely used in traditional Chinese medicine for the treatment of ulcerative colitis. The objective of this study was to explore the therapeutic basis of the dried bark of Ailanthus altissima (Mill.) Swingle for the treatment of ulcerative colitis based on Virtual Screening–Molecular Docking–Activity Evaluation technology. Methods By searching the Traditional Chinese Medicine Systems Pharmacology TCMSP Database and Analysis Platform, 89 compounds were obtained from the chemical components of the dried bark of Ailanthus altissima (Mill.) Swingle. Then, after preliminarily screening the compounds based on Lipinski’s rule of five and other relevant conditions, the AutoDock Vina molecular docking software was used to evaluate the affinity of the compounds to ulcerative colitis-related target proteins and their binding modes through use of the scoring function to identify the best candidate compounds. Further verification of the compound’s properties was achieved through in vitro experiments. Results Twenty-two compounds obtained from the secondary screening were molecularly docked with ulcerative colitis-related target proteins (IL-1R, TLR, EGFR, TGFR, and Wnt) using AutoDock Vina. The free energies of the highest scoring compounds binding to the active cavity of human IL-1R, TLR, EGFR, TGFR, and Wnt proteins were − 8.7, − 8.0, − 9.2, − 7.7, and − 8.5 kcal/mol, respectively. The potential compounds, dehydrocrebanine, ailanthone, and kaempferol, were obtained through scoring function and docking mode analysis. Furthermore, the potential compound ailanthone (1, 3, and 10 µM) was found to have no significant effect on cell proliferation, though at 10 µM it reduced the level of pro-inflammatory factors caused by lipopolysaccharide. Conclusion Among the active components of the dried bark of Ailanthus altissima (Mill.) Swingle, ailanthone plays a major role in its anti-inflammatory properties. The present study shows that ailanthone has advantages in cell proliferation and in inhibiting of inflammation, but further animal research is needed to confirm its pharmaceutical potential.

Abstract Background Globally, despite prostate cancer (PCa) representing second most prevalent malignancy in male, the precise molecular mechanisms implicated in its pathogenesis remain unclear. Consequently, elucidating the key molecular regulators that govern disease progression could substantially contribute to the establishment of novel therapeutic strategies, ultimately advancing the management of PCa. Methods A total of 49 PCa tissues and 43 adjacent normal tissues were collected from January 2017 to December 2021 at Zhongnan Hospital of Wuhan University. The advanced transcriptomic methodologies were employed to identify differentially expressed mRNAs in PCa. The expression of aspartoacylase (ASPA) in PCa was thoroughly evaluated using quantitative real-time PCR and Western blotting techniques. To elucidate the inhibitory role of ASPA in PCa cell proliferation and metastasis, a comprehensive set of in vitro and in vivo assays were conducted, including orthotopic and tumor-bearing mouse models (n = 8 for each group). A combination of experimental approaches, such as Western blotting, luciferase assays, immunoprecipitation assays, mass spectrometry, glutathione S-transferase pull-down experiments, and rescue studies, were employed to investigate the underlying molecular mechanisms of ASPA’s action in PCa. The Student’s t-test was employed to assess the statistical significance between two distinct groups, while one-way analysis of variance was utilized for comparisons involving more than two groups. A two-sided P value of less than 0.05 was deemed to indicate statistical significance. Results ASPA was identified as a novel inhibitor of PCa progression. The expression of ASPA was found to be significantly down-regulated in PCa tissue samples, and its decreased expression was independently associated with patients’ prognosis (HR = 0.60, 95% CI 0.40–0.92, P = 0.018). Our experiments demonstrated that modulation of ASPA activity, either through gain- or loss-of-function, led to the suppression or enhancement of PCa cell proliferation, migration, and invasion, respectively. The inhibitory role of ASPA in PCa was further confirmed using orthotopic and tumor-bearing mouse models. Mechanistically, ASPA was shown to directly interact with the LYN and inhibit the phosphorylation of LYN as well as its downstream targets, JNK1/2 and C-Jun, in both PCa cells and mouse models, in an enzyme-independent manner. Importantly, the inhibition of LYN activation by bafetinib abrogated the promoting effect of ASPA knockdown on PCa progression in both in vitro and in vivo models. Moreover, we observed an inverse relationship between ASPA expression and LYN activity in clinical PCa samples, suggesting a potential regulatory role of ASPA in modulating LYN signaling. Conclusion Our findings provide novel insights into the tumor-suppressive function of ASPA in PCa and highlight its potential as a prognostic biomarker and therapeutic target for the management of this malignancy.

The tack of prepreg is a key factor affecting the automatic tape laying process. During the manufacturing process of large composite parts, prepreg material may be stored at room temperature for several days, resulting in a decrease in its tack. In this study, a new tack test tool was designed, and the decay rate of prepreg tack at different temperatures was tested. We proposed a prepreg tack decay model, which assumes that the main factor in tack decay is the reduction in resin chain activity during storage. The maximum deviation between the model calculation results and the experimental results of the tack decay rate is 9.7%. This study also proposed a new statistical unit for prepreg tack, which can establish the relationship between the tack of prepreg and its remaining storage time and reduce prepreg management costs.

Flos Sophorae (FS), or the dried flower buds of Sophora japonica L., is widely used as a food and medicinal material in China. The quality of S. japonica flowers varies with the developmental stages (S1–S5) of the plant. However, the relationship between FS quality and maturity remains unclear. Inductively coupled plasma optical emission spectrometry (ICP-OES) and ultra-high performance liquid chromatography coupled with electrospray ionization-triple quadrupole-linear ion trap mass spectrometry (UPLC-ESI-Q TRAP-MS/MS) were used to analyze inorganic elements and flavonoid metabolites, respectively. A combined analysis of the inorganic elements and flavonoid metabolites in FS was conducted to determine the patterns of FS quality formation. Sixteen inorganic elements and 173 flavonoid metabolites that accumulated at different developmental stages were identified. Notably, 54 flavonoid metabolites associated with the amelioration of major human diseases were identified, and Ca, P, K, Fe, and Cu were postulated to influence flavonoid metabolism and synthesis. This study offers a novel perspective and foundation for the further exploration of the rules governing the quality of plant materials.

Echinacoside, a natural phenylethanoid glycoside, was discovered and isolated from the garden plant Echinacea angustifolia DC., belonging to the Compositae family, approximately sixty years ago. Extensive investigations have revealed that it possesses a wide array of pharmacologically beneficial activities for human health, particularly notable for its neuroprotective and anticancer activity. Several crucial concerns surfaced, encompassing the recognition of active metabolites that exhibited inadequate bioavailability in their prototype form, the establishment of precise molecular signal pathways or targets associated with the aforementioned effects of echinacoside, and the scarcity of dependable clinical trials. Hence, the question remains unanswered as to whether scientific research can effectively utilize this natural compound. To support future studies on this natural product, it is imperative to provide a systematic overview and insights into potential future prospects. The current review provides a comprehensive analysis of the existing knowledge on echinacoside, encompassing its wide distribution, structural diversity and metabolism, diverse therapeutic applications, and improvement of echinacoside bioavailability for its potential utilization.

Introduction: Stem cells and scaffolds are an important foundation and starting point for tissue engineering. Human dental pulp stem cells (DPSC) are mesenchymal stem cells with self-renewal and multi-directional differentiation potential, and are ideal candidates for tissue engineering due to their excellent biological properties and accessibility without causing major trauma at the donor site. Tetracycline hydrochloride (TCH), a broad-spectrum antibiotic, has been widely used in recent years for the synthesis of cellular scaffolds to reduce the incidence of postoperative infections.Methods: In order to evaluate the effects of TCH on DPSC, the metabolism of DPSC in different concentrations of TCH environment was tested. Moreover, cell morphology, survival rates, proliferation rates, cell migration rates and differentiation abilities of DPSC at TCH concentrations of 0–500 μg/ml were measured. Phalloidin staining, live-dead staining, MTS assay, cell scratch assay and real-time PCR techniques were used to detect the changes in DPSC under varies TCH concentrations.Results: At TCH concentrations higher than 250 μg/ml, DPSC cells were sequestered, the proportion of dead cells increased, and the cell proliferation capacity and cell migration capacity decreased. The osteogenic and adipogenic differentiation abilities of DPSC, however, were already inhibited at TCH con-centrations higher than 50 μg/ml. Here, the expression of the osteogenic genes, runt-related transcription factor 2 (RUNX2) and osteocalcin (OCN), the lipogenic genes lipase (LPL), as well as the peroxisome proliferator-activated receptor-γ (PPAR-γ) expression were found to be down-regulated.Discussion: The results of the study indicated that TCH in concentrations above 50 µg/ml negatively affects the differentiation capability of DPSC. In addition, TCH at concentrations above 250 µg/ml adversely affects the growth status, percentage of living cells, proliferation and migration ability of cells.