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The all-d-metal Ni–Mn–Ti Heusler alloy with its good mechanical properties and colossal caloric effects has attracted significant attention for mechanocaloric refrigeration. However, the phase stability of the B2-type disordered structure at finite temperatures and the physical origin of large phase transformation entropy change in theoretical calculation remain unclear. In view of thermal and strongly anharmonic effects, we combined the first-principles and temperature dependent effective potential calculations to systematically study the phase stability, martensitic transformation mechanism, and vibrational entropy properties of B2 partial disordered structures for Ni8Mn5Ti3 and Ni8Mn6Ti2. Our results showed the austenitic structures of Ni8Mn5Ti3 and Ni8Mn6Ti2 both exhibit antiferromagnetic interaction behaviors at targeted temperatures, resolving the contradiction between previous calculations and experiments. By the analysis of phonon dispersion relations and Helmholtz free energies at low and high temperatures, we provided a deeper explanation for the underlying mechanism of martensitic transformation. Meanwhile, the phase transformation temperatures and vibrational entropy changes were accurately predicted compared with the experiment results. Specifically, we demonstrated that the large vibrational entropy change of Ni–Mn–Ti material originates from the contributions of both the tetragonal distortion ratio and volume change, which provides important theoretical guidance and has great practical significance for designing the solid-state material with large vibrational entropy change in the application of solid-state refrigeration.

Superelasticity of shape memory alloy associated with the martensitic transformation is extremely attractive for applications in sensors and biomedical. This application requires narrow stress hysteresis to reduce energy dissipation and a stable superelasticity cycle is an important factor in their practical applications. Co–V–Al alloys have inimitable advantages due to their narrow stress hysteresis, low-cost, and corrosion resistance, but the low number of superelasticity cycles restricts its development. Here, we report an intrinsic Co58V29Al13 polycrystalline alloy with a superelasticity stress hysteresis of 30 MPa at room temperature, the lowest among the alloys in this system, and a superelasticity strain of 3.6%. In addition, the sample shows no significant decay trend after 500 loading and unloading cycles. The high number of superelasticity cycles is mainly due to the elastic stress field generated around the dislocation during the cycle, which provides internal stress for martensite nucleation and reduces energy dissipation during martensitic transformation. This work provides essential guiding significance for the design of high-performance superelasticity alloys.

Currently, practical applications of shape memory alloy (SMA) solid elastocaloric refrigeration materials are limited by low elastocaloric effect (eCE), high applied stress, and large stress hysteresis (Δσhys). Here, we introduce a composition design strategy using Ti-doped Co–V-Ga SMAs to address these challenges. We combine first-principles calculations and experiments to verify this strategy. Our results show that the lattice distortion caused by the significant difference in atomic radius after Ti doping produces a solid solution strengthening effect inside the alloy, which significantly improves the superelasticity of the alloy, delays the plastic deformation of the austenite phase, and the volume fraction of martensitic transformation increases significantly. The newly developed Co51.7V31.3Ga16Ti1 bulk polycrystalline alloy exhibits a remarkable adiabatic temperature change (ΔTad) of −10 K at room temperature under a low stress of 400 MPa, a minimum Δσhys of 18 MPa, and a high coefficient of performance COPmat of 31.9. Importantly, the 100-cycle loading-unloading test at 350 MPa is done, and it reveals that the ΔTad for the Ti0 alloy was only 3.9 K, while it reached 6.2 K for the Ti1 alloy, marking a noteworthy 59 % performance enhancement. From the simplicity of the fabrication process to the comprehensive performance of the material, it exhibits a promising advantage for practical cooling applications This study presents a feasible design strategy for large-scale production of high-performance bulk polycrystalline alloys with high eCE, low stress, and Δσhys.

A type of integrated multiple-single-channel analyzer (IMSCA) is described. The IMSCA works with an input pulse of 2-20 pC, and it can be directly connected to a scintillation detector, which eliminates the need for a linear amplifier. It consists of 64 input ports, so 1–64 detectors can be set by users according to different requirements. Two energy regions for each input channel can be simultaneously analyzed. Another advantage of the IMSCA is that it integrates with a high-speed pulse signal acquisition card and transmits data to the computer through the network. The maximum pulse through-rate is 1.4 MHz, and linearity can reach 0.1%. This IMSCA has been successfully used in enrichment detecting of nuclear fuel rod.

Achieving a balance between convergence and diversity and their mutual enhancement is a complex task in the process of algorithm improvement. This is crucial because it is directly related to the effectiveness of the algorithm in obtaining accurate and uniformly distributed Pareto frontiers. Although significant progress has been made in particle swarm algorithms, exploring new approaches is necessary. In this paper, we construct a projection plane (projection line in 2D) based on the extreme values of the non-dominated solutions, select a set of uniform reference points on the projection plane, and then project the non-dominated solutions onto the constructed projection plane to form projection points. The reference points and projection points on the projection plane are thus utilized to guide the updating of the population as well as the maintenance of the external archive, a strategy that enhances the algorithm's global exploration and local exploitation capabilities. Secondly, we aggregate the target values of particles into a single scalar value and combine the idea of particle fusion to design a scheme for the particle selection of individual optimal particles. This paper further improves the algorithm's overall performance by using the information between populations to select individual optimal particles. Lastly, it is evaluated against a number of multi-objective algorithms that are currently in use and perform well on 22 test problems. The findings demonstrate that the algorithm this paper proposes performs better when solving multi-objective problems.

There is currently no effective targeted therapeutic strategy for the treatment of central nervous system acute lymphoblastic leukemia (CNS-ALL). Integrin α6 is considered a potential target for CNS-ALL diagnosis and therapy because of its role in promoting CNS-ALL disease progression. The targeted peptide D(RWYD) (abbreviated RD), with nanomolar affinity to integrin α6 was identified by peptide scanning techniques such as alanine scanning, truncation, and D-substitution. Herein, we developed a therapeutic nanoparticle based on the integrin α6-targeted peptide for treating CNS-ALL. The self-assembled proapoptotic nanopeptide D(RWYD)-D(KLAKLAK)2-GD(FFY) (abbreviated RD-KLA-Gffy) contains the integrin α6-targeted peptide RD, the well-known proapoptotic peptide D(KLAKLAK)2 (abbreviated KLA), and the self-assembling tetrapeptide GD(FFY) (abbreviated Gffy). The functional mechanism of RD-KLA-Gffy is clarified using different experiments. Our results demonstrate that RD-KLA-Gffy is highly enriched in CNS-ALL lesions and induces tumor cell apoptosis, thus reducing CNS-ALL disease burden and prolonging the survival of CNS-ALL mice without obvious toxicity. Moreover, the combined use of RD-KLA-Gffy and methotrexate (MTX) shows a potent antitumor effect in treating CNS-ALL, indicating that RD-KLA-Gffy plays an important role in suppressing CNS-ALL progression either as a single agent or in combination with MTX, which shows promise for application in CNS-ALL therapy.

Pulmonary hypertension (PH) is a fatal disorder characterized by pulmonary vascular remodeling and obstruction. The phosphodiesterase 4 (PDE4) family hydrolyzes cyclic AMP (cAMP) and is comprised of four subtypes (PDE4A–D). Previous studies have shown the beneficial effects of pan-PDE4 inhibitors in rodent PH; however, this class of drugs is associated with side effects owing to the broad inhibition of all four PDE4 isozymes. Here, we demonstrate that PDE4B is the predominant PDE isozyme in lungs and that it was upregulated in rodent and human PH lung tissues. We also confirmed that PDE4B is mainly expressed in the lung endothelial cells (ECs). Evaluation of PH in Pde4b wild type and knockout mice confirmed that Pde4b is important for the vascular remodeling associated with PH. In vivo EC lineage tracing demonstrated that Pde4b induces PH development by driving endothelial-to-mesenchymal transition (EndMT), and mechanistic studies showed that Pde4b regulates EndMT by antagonizing the cAMP-dependent PKA–CREB–BMPRII axis. Finally, treating PH rats with a PDE4B-specific inhibitor validated that PDE4B inhibition has a significant pharmacological effect in the alleviation of PH. Collectively, our findings indicate a critical role for PDE4B in EndMT and PH, prompting further studies of PDE4B-specific inhibitors as a therapeutic strategy for PH.

In solar energy utilization, photocatalytic hydrogen production has been widely researched. To address issues such as low efficiency of photocatalysts, Cu-doped Zn0.5Cd0.5S composite photocatalysts were prepared using a hydrothermal method for photocatalytic hydrogen production. The Cu/Zn0.5Cd0.5S photocatalyst was characterized using XRD, XPS, SEM, TEM, UV–vis-DRS, fluorescence spectrophotometer, and electrochemical workstation. The results indicate that Cu doping alters the crystal and band structures of Zn0.5Cd0.5S. Hydrogen production experiments were conducted under xenon lamp irradiation, and at 45 °C, the highest hydrogen production rate was 2.72 and 1.63 times that of single Zn0.5Cd0.5S and Cu-doped Zn0.5Cd0.5S at room temperature (25 °C), respectively. Cu doping imparted a photothermal effect to the photocatalytic hydrogen production experiment, enhancing its efficiency.Cu doping captured electrons by replacing some Zn, constructing an internal electric field, forming defect energy levels, which hindered electron-hole recombination. Additionally, Cu ions acted as a plasma, inducing a plasma effect during hydrogen production, accelerating the rate of solar energy conversion to thermal energy, thus improving hydrogen production efficiency. This research not only provides a photocatalyst for photocatalytic hydrogen production but also utilizes it for photothermal synergistic catalysis.

Due to the significantly higher wind energy density in high-latitude sea areas compared to other regions, the construction of offshore wind farms is shifting towards these areas. However, in high-latitude sea areas, large amounts of sea ice float on the surface during winter, making ice loads a critical factor affecting the structural safety of wind turbines. For monopile flexible wind turbines, installing an ice-breaking cone near the waterline is an effective measure to withstand the threat of sea ice. To clarify the ice resistance performance of conical wind turbine foundations in brash ice zones, this study proposes a coupled Computational Fluid Dynamics-Discrete Element Method (CFD-DEM). This method is used to calculate the ice load results for a cylindrical riser, and the results were found to be in good agreement with the ice load experiment results from China University of Petroleum's wave flume (CUPWF). This validation confirms the rationality of the method. Taking a 5 MW monopile wind turbine installed with an ice-breaking cone as the research object, the time history of dynamic ice loads and the displacement response of ice-induced vibration during the interaction between the wind turbine and brash ice are simulated. Considering the water level variations caused by tides, the differences in ice resistance performance between the upright cone and the inverted cone of the ice-breaking cone are analyzed. Finally, the impact of changes in cone angle on the ice resistance performance of the wind turbine foundation is determined. The results indicate that under the impact of brash ice, the upright cone of the ice-breaking cone has a higher ice resistance capacity compared to the inverted cone. With changes in cone angle, the trends of ice loads in the horizontal and vertical directions vary oppositely. However, the overall ice resistance capacity of the wind turbine foundation decreases as the cone angle increases. This study can provide a reference for the rational design of conical wind turbines in cold regions.

Bisphenol A (BPA), a typical environmental endocrine disruptor, has raised concerns among researchers due to its toxicological effects. Whether neohesperidin (NEO) can intervene in the toxic effects of BPA remains unknown. This study aims to investigate the effects and mechanisms of NEO on the myogenic differentiation of umbilical cord-derived mesenchymal stem cells (UC-MSCs) exposed to BPA. Sheep UC-MSCs were isolated, characterized, and induced to myogenic differentiation. BPA decreased cell viability, cell migration, and the expressions of myogenic marker genes, leading to myogenic differentiation inhibition, which were reversed by NEO. Network pharmacology suggested the IGF1R/AKT1/RHOA pathway as potential targets of BPA and NEO regulating muscle development. Western blot results showed that NEO could reverse the down-regulation of the pathway proteins induced by BPA, and counteract the effects of picropodophyllin (PPP) or MK-2206 dihydrochloride (MK-2206) in the myogenic differentiation of sheep UC-MSCs. Additionally, the expression levels of (p-) IGF1R, AKT1, and RHOA were positively correlated. Taken together, the mechanisms of NEO resistance to BPA involved the IGF1R/AKT1/RHOA signaling pathway. These findings provide a scientific basis for alleviating BPA toxicity, preventing and treating muscular dysplasia, and promoting muscle damage repair.

Atherosclerosis (AS) is a prevalent chronic vascular inflammatory disease globally, initiated by injury to vascular endothelial cells (VECs). Macrophages play a pivotal role in disease pathogenesis, involving lipid metabolism and inflammation. The application of nanomaterials has been hindered by their rapid clearance by the immune system. Utilizing macrophage cell membranes can mitigate abnormal immune responses and induce a ''homing'' effect. Here, M2 macrophage cell membranes (M2) were coated onto berberine polylactic-hydroxylase-polylactide (PLGA) nanoparticles (BBR NPs), employing M2 macrophage immune escape, ''homing'' ability, and membrane coating nanotechnology, and loaded with mannose (Man) to create bionic nanoparticles (BBR NPs@Man/M2). Subsequently, the physical properties of BBR NPs@Man/M2 were characterized. The biocompatibility and biological function of BBR NPs@Man/M2 were assessed in vitro. Finally, the targeting, therapeutic efficacy, and safety of BBR NPs@M2 were investigated in an AS mouse model. The newly developed BBR NPs@Man/M2 exhibited good biocompatibility. Owing to their M2 coating, the nanoparticles effectively targeted macrophages in vitro, inducing a shift from a pro-inflammatory to an anti-inflammatory state. This transition reduced inflammation in endothelial cells and facilitated the repair of damaged endothelial cells. Moreover, M2-coated nanoparticles efficiently targeted and accumulated in atherosclerotic lesions in vivo. Following four weeks of treatment, BBR NPs@Man/M2 significantly delayed AS progression. Furthermore, BBR NPs@Man/M2 demonstrated a good safety profile after long-term administration. In conclusion, BBR NPs@Man/M2 effectively and safely inhibited AS progression. Biomimetic nanoparticles represent a promising approach for the safe and effective delivery of anti-AS drugs.

Summary: Pancreatic cancer is highly lethal with limited effective treatments. This study explores the therapeutic effects of eupalinolide B (EB) from Eupatorium lindleyanum DC on pancreatic cancer cells. Through cellular functional assays, we observed that EB effectively inhibits cell viability, proliferation, migration, and invasion. In a xenograft mouse model, EB treatment resulted in reduced pancreatic cancer tumor growth and decreased expression of Ki-67. Mechanistically, EB induces apoptosis, elevates reactive oxygen species (ROS) levels, and disrupts copper homeostasis. RNA sequencing (RNA-seq) and gene set enrichment analysis (GSEA) identified copper ion binding pathways and potential involvement in cuproptosis. Furthermore, EB enhances the cytotoxic effects of elesclomol (ES), increasing ROS levels in a copper-dependent manner and exhibiting synergistic cytotoxicity. These findings suggest that EB, either alone or in combination with ES, represents a promising strategy for targeting metal ion dysregulation and inducing potential cuproptosis in pancreatic cancer, offering a potential improvement in therapeutic outcomes.

Summary: Background: In non-high-risk individuals, risk-category-based atherosclerotic cardiovascular disease (ASCVD) screening strategies may be more cost-effective than one-size-fits-all approaches. However, current decisions are constrained by a lack of research evidence. We aimed to explore appropriate risk-category-based screening interval strategies for non-high-risk individuals in ASCVD primary prevention in the Chinese population. Methods: We used data from 28,624 participants in the China Kadoorie Biobank (CKB) who had completed at least two field surveys. The risk assessment tools were the 10-year ASCVD risk prediction models developed based on the CKB cohort. We constructed multistate Markov models to model disease progression and estimate transition probabilities between different risk categories. The total person-years spent unidentified in the high-risk state over a 10-year period were calculated for each screening interval protocol. We also estimated the number of ASCVD events prevented, quality-adjusted life years (QALYs) gained, and costs saved when compared to the 3-yearly screening protocol. Findings: When compared to the uniform 3-yearly protocol, most risk-category-based screening interval protocols would identify more high-risk individuals timely, thus preventing more ASCVD events and gaining QALYs. A few of them would reduce total health-care costs. The protocol, which used 6-year, 3-year, and 2-year screening intervals for low-risk, intermediate-low-risk, and intermediate-high risk individuals, was optimal, and would reduce the person-years spent unidentified in the high-risk category by 17.9% (95% CI: 13.1%–21.9%), thus preventing an estimated 113 thousand (95% CI: 83–138) hard ASCVD events for Chinese adults aged 30–79 over a 10-year period. When using a lower cost of statin therapy, more screening protocols would gain QALYs while saving costs. Interpretation: For the primary prevention of ASCVD, risk-category-based screening protocols outperformed the one-size-fits-all approach in the Chinese population. Funding: This work was supported by National Natural Science Foundation of China (82192904, 82388102, 82192900) and grants (2023YFC2509400) from the National Key R&D Program of China. The CKB baseline survey and the first re-survey were supported by a grant from the Kadoorie Charitable Foundation in Hong Kong. The long-term follow-up is supported by grants from the UK Wellcome Trust (212946/Z/18/Z, 202922/Z/16/Z, 104085/Z/14/Z, 088158/Z/09/Z), grants (2016YFC0900500) from the National Key R&D Program of China, National Natural Science Foundation of China (81390540, 91846303, 81941018), and Chinese Ministry of Science and Technology (2011BAI09B01).

Neural stem cells (NSCs) exhibit a remarkable capacity for self-renewal and have the potential to differentiate into various neural lineage cells, which makes them pivotal in the management of neurological disorders. Harnessing the inherent potential of endogenous NSCs for enhancing nerve repair and regeneration represents an optimal approach to addressing diseases of the nervous system. In this study, we explored the potential of a novel benzophenone derivative named Digirseophene A (DGA), which was isolated from the endophytic fungus Corydalis tomentella. Previous experiments have extensively identified and characterized DGA, revealing its unique properties. Our findings demonstrate the remarkable capability of DGA to stimulate neural stem cell proliferation, both in vitro and in vivo. Furthermore, we established a model of radiation-induced cerebellar injury to assess the effects of DGA on the distribution of different cell subpopulations within the damaged cerebellum, thereby suggesting its beneficial role in cerebellar repair. In addition, our observations on a primary NSCs model revealed that DGA significantly increased cellular oxygen consumption, indicating increased energy and metabolic demands. By utilizing various pathway inhibitors in combination with DGA, we successfully demonstrated its ability to counteract the suppressive impacts of AMPK and GSK3β inhibitors on NSC proliferation. Collectively, our research results strongly suggest that DGA, as an innovative compound, exerts its role in activating NSCs and promoting injury repair through the regulation of the AMPK/AKT/GSK3β pathway.

In the study of cavitation in room-temperature fluids, the heat transfer between gas and liquid in bubble oscillation is usually assumed to be an adiabatic process for simplification. However, this heat transfer and thermodynamic mechanism is not yet understood in cryogenic fluids, especially under small amplitude oscillation conditions excited by ultrasonic field. This article studies bubble thermodynamic model under an external ultrasonic field based on the heat transfer equation for cryogenic fluids. The temperature changes inside bubbles are calculated, and the heat transfer mechanism is briefly analyzed. The results indicate that the heat transfer mechanism of bubbles depends on the relationship between ultrasonic frequency and bubble resonance frequency. By analyzing two special cases of dual-bubble and high-pressure environment, it is believed that heat transfer can be approximated as an adiabatic process under high-pressure conditions with ultrasonic frequency far from the resonance frequency. This conclusion can provide a theoretical basis for subsequent accurate calculation of heat-transfer polytropic coefficient, or void faction measurement in cryogenic two-phase flow.

Background: 5-Fluorouracil (5-Fu), a prominent chemotherapeutic agent for colorectal cancer (CRC) treatment, is often associated with gastrointestinal toxicities, particularly diarrhea. Our previous study demonstrated that berberine (BBR) ameliorates 5-Fu-induced intestinal mucosal injury by modulating the gut microbiota in rats. Nevertheless, the precise molecular mechanism underlying BBR's protective effect on intestinal mucosa remains elusive, and its impact on the anti-tumor efficacy of 5-Fu warrants further investigation. Methods: The effect of BBR on 5-Fu-induced intestinal mucosal injury was investigated using a tumor-bearing murine model, employing H&E staining, 16 S rDNA sequencing, transcriptome sequencing, Western blot analysis, cell experiments and constructing a pseudo-germ-free tumor xenograft model. Result: Our findings demonstrate that BBR alleviates intestinal mucosal damage, reduces the levels of inflammatory factors (IL-6, TNF-α, and IL-1β), and inhibits epithelial cell apoptosis in 5-Fu-treated mice without compromising 5-Fu's anti-tumor efficacy. Moreover, 16 S rDNA sequencing indicated that BBR significantly increases the abundance of Akkermansia and decreases the abundance of pathogenic bacteria Escherichia/Shigella at the genus level. Mechanistically, transcriptome sequencing and Western blot analysis confirmed that BBR upregulates PI3K/AKT/mTOR expression in the intestinal mucosa. However, this effect was not observed in tumor tissues. Notably, BBR did not demonstrate a direct protective effect on 5-Fu-treated CCD841 and SW480 cells. Additionally, BBR had no effect on the PI3K/AKT/mTOR pathway in the intestinal tissue of the 5-Fu-treated mouse model with a depleted gut microbiota. Conclusion: This study indicates that BBR alleviates 5-Fu-induced intestinal mucosal injury by modulating the gut microbiota and regulating the PI3K/AKT/mTOR signaling pathway without compromising the anti-tumor efficacy of 5-Fu.

Summary: Methicillin-resistant Staphylococcus aureus (MRSA) infection, a major cause of hospital- and community-acquired pneumonia, still has a high mortality rate. Extracellular vesicles (EVs), as crucial mediators of intercellular communication, have a significant impact on infectious diseases. However, the role of EVs from alveolar macrophages (AMs) in MRSA pneumonia remains unclear. We report that AMs phagocytose MRSA and release more EVs in mice with MRSA pneumonia. EVs from AMs harboring phagocytosed MRSA exhibit significant proinflammatory effects and induce necroptosis by delivering tumor necrosis factor α (TNF-α) and miR-146a-5p. Mechanically, the upregulated miR-146a-5p in these EVs enhances the phosphorylation of RIPK1, RIPK3, and MLKL by targeting TNF receptor-associated factor 6 (TRAF6), thereby promoting TNF-α-induced necroptosis. The combination of a TNF-α antagonist and an miR-146a-5p antagomir effectively improves the outcomes of mice with MRSA pneumonia. Overall, we reveal the pronecrotic effect of EVs from MRSA-infected AMs and provide a promising target for the prevention and treatment of MRSA pneumonia.

Doxorubicin (Dox) is an anti-tumor drug with a broad spectrum, whereas the cardiotoxicity limits its further application. In clinical settings, liposome delivery vehicles are used to reduce Dox cardiotoxicity. Here, we substitute extracellular vesicles (EVs) for liposomes and deeply investigate the mechanism for EV-encapsulated Dox delivery. The results demonstrate that EVs dramatically increase import efficiency and anti-tumor effects of Dox in vitro and in vivo, and the efficiency increase benefits from its unique entry pattern. Dox-loading EVs repeat a “kiss-and-run” motion before EVs internalization. Once EVs touch the cell membrane, Dox disassociates from EVs and directly enters the cytoplasm, leading to higher and faster Dox import than single Dox. This unique entry pattern makes the adhesion between EVs and cell membrane rather than the total amount of EV internalization the key factor for regulating the Dox import. Furthermore, we recognize ICAM1 as the molecule mediating the adhesion between EVs and cell membranes. Interestingly, EV-encapsulated Dox can induce ICAM1 expression by irritating IFN-γ and TNF-α secretion in TME, thereby increasing tumor targeting of Dox-loading EVs. Altogether, EVs and EV-encapsulated Dox synergize via ICAM1, which collectively enhances the curative effects for tumor treatment.

Constitutive activation of GNAQ/11 is the initiative oncogenic event in uveal melanoma (UM). Direct targeting GNAQ/11 has yet to be proven feasible as they are vital for a plethora of cellular functions. In search of genetic vulnerability for UM, we found that inhibition of euchromatic histone lysine methyltransferase 2 (EHMT2) expression or activity significantly reduced the proliferation and migration capacity of cancer cells. Notably, elevated expression of EHMT2 had been validated in UM samples. Furthermore, Kaplan–Meier survival analysis indicated high EHMT2 protein level was related to poor recurrence-free survival and a more advanced T stage. Chromatin immunoprecipitation sequencing analysis and the following mechanistic investigation showed that ARHGAP29 was a downstream target of EHMT2. Its transcription was suppressed by EHMT2 in a methyltransferase-dependent pattern in GNAQ/11-mutant UM cells, leading to elevated RhoA activity. Rescuing constitutively active RhoA in UM cells lacking EHMT2 restored oncogenic phenotypes. Simultaneously blocking EHMT2 and GNAQ/11 signaling in vitro and in vivo showed a synergistic effect on UM growth, suggesting the driver role of these two key molecules. In summary, our study shows evidence for an epigenetic program of EHMT2 regulation that influences UM progression and indicates inhibiting EHMT2 and MEK/ERK simultaneously as a therapeutic strategy in GNAQ/11-mutant UM.

Context: Data on racial disparities among patients with metastatic castration-resistant prostate cancer (mCRPC) are limited and there is no uniform conclusion on differences by race in this setting. Objective: To provide the latest evidence on racial disparities in survival outcomes between Black and White patients receiving systemic therapies for mCRPC. Evidence acquisition: Our study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. We systematically searched the PubMed, Web of Science, and Cochrane Library databases up to September 2023 to identify potentially relevant studies. Overall survival (OS) and progression-free survival (PFS) were the outcomes of interest. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were evaluated. Evidence synthesis: Nine studies involving 9462 patients with mCRPC (2058 Black and 7404 White men) met the eligibility criteria and were included. Pooled estimates demonstrated significantly better OS for Black than for White men (HR 0.75, 95% CI 0.70–0.80; p

Objective: To reveal the molecular mechanism underlying the compatibility of Salvia miltiorrhiza Bge (S. miltiorrhiza, Dan Shen) and C. tinctorius L. (C. tinctorius, Hong Hua) as an herb pair through network pharmacology and subsequent experimental validation. Methods: Network pharmacology was applied to construct an active ingredient-efficacy target-disease protein network to reveal the unique regulation pattern of S. miltiorrhiza and C. tinctorius as herb pair. Molecular docking was used to verify the binding of the components of these herbs and their potential targets. An H9c2 glucose hypoxia model was used to evaluate the efficacy of the components and their synergistic effects, which were evaluated using the combination index. Western blot was performed to detect the protein expression of these targets. Results: Network pharmacology analysis revealed 5 pathways and 8 core targets of S. miltiorrhiza and C. tinctorius in myocardial protection. Five of the core targets were enriched in the hypoxia-inducible factor-1 (HIF-1) signaling pathway. S. miltiorrhiza-C. tinctorius achieved vascular tone mainly by regulating the target genes of the HIF-1 pathway. As an upstream gene of the HIF-1 pathway, STAT3 can be activated by the active ingredients cryptotanshinone (Ctan), salvianolic acid B (Sal. B), and myricetin (Myric). Cell experiments revealed that Myric, Sal. B, and Ctan also exhibited synergistic myocardial protective activity. Molecular docking verified the strong binding of Myric, Sal. B, and Ctan to STAT3. Western blot further showed that the active ingredients synergistically upregulated the protein expression of STAT3. Conclusion: The pharmacodynamic transmission analysis revealed that the active ingredients of S. miltiorrhiza and C. tinctorius can synergistically resist ischemia through various targets and pathways. This study provides a methodological reference for interpreting traditional Chinese medicine compatibility.

With the rapid development of solid-state refrigeration technology, elastocaloric materials face higher requirements, such as a higher elastocaloric effect (eCE), better mechanical properties, and simpler and faster large-scale preparation. In this work, we propose a composition design strategy for Mn-doped Co–V-Ga shape memory alloys, which can enhance both the eCE and the mechanical properties. We combine first-principles calculations and experiments to demonstrate this strategy. Our results reveal that the lattice distortion caused by the difference in atomic radii produces a solid-solution-strengthening effect within the alloy, impeding dislocation motion and significantly improving the mechanical properties. Through composition optimization, the low-cost Co51.7V31.3Ga14.75Mn2.25 as-cast polycrystalline alloy exhibits a large adiabatic temperature change (ΔTad) of −11.2 K at room temperature, while its maximum compressive strength and strain can reach up to 1859 MPa and 26% at room temperature, respectively. Importantly, the alloy exhibits excellent cycle stability, and its ΔTad does not decay after 100 loading and unloading cycles, indicating that it has the potential for practical application. Further comparison with the annealed sample shows that the secondary defects deteriorate the ΔTad of the alloy. Our research provides an effective strategy for the simple, rapid and large-scale production of as-cast eCE alloys.

In future regenerative medicine, far-infrared radiation (FIR) may be an essential component of optical therapy. Many studies have confirmed or validated the efficacy and safety of FIR in various diseases, benefiting from new insights into FIR mechanisms and the excellent performance of many applications. However, the lack of consensus on the biological effects and therapeutic parameters of FIR limits its practical applications in the clinic. In this review, the definition, characteristics, and underlying principles of the FIR are systematically illustrated. We outline the therapeutic parameters of FIR, including the wavelength range, power density, irradiation time, and distance. In addition, the biological effects, potential molecular mechanisms, and preclinical and clinical applications of FIR are discussed. Furthermore, the future development and applications of FIR are described in this review. By applying optimal therapeutic parameters, FIR can influence various cells, animal models, and patients, eliciting diverse underlying mechanisms and offering therapeutic potential for many diseases. FIR could represent a superior alternative with broad prospects for application in future regenerative medicine.

ABSTRACT: Enteric glial cell (EGC) is involved in neuroimmune regulation within the enteric nervous system (ENS); however, limited information exists on the distribution and ultrastructure of EGC in the poultry gut. We aim to investigate the morphological features and distribution of EGC in the chicken cecum. Here, we investigated the distribution and ultrastructural features of chicken cecum EGC using immunohistochemistry (IHC) and transmission electron microscopy (TEM). IHC showed that EGC was widely distributed throughout the chicken cecum. In the mucosal layer, EGC was morphologically irregular, with occasionally interconnecting protrusions that outlined signal-negative neurons. The morphology of EGC in the submucosal layer was also irregular. In the inner circular muscle layer and between the inner circular and outer longitudinal muscle layers, EGC aligned parallel to the circular muscle cells. A small number of EGC with an irregular morphology were found in the outer longitudinal muscle layer. In addition, in the submucosal and myenteric plexus, EGC were aggregated, and the protrusions of the immunoreactive cells interconnected to outline the bodies of nonreactive neurons. TEM-guided ultrastructural characterization confirmed the IHC findings that EGC were morphologically irregular and revealed they developed either a star, bipolar, or fibrous shape. The nucleus was also irregular, with electron-dense heterochromatin distributed in the center of the nucleus or on the nuclear membrane. The cytoplasm contained many glial filaments and vesicle-containing protrusions from neuronal cells; organelles were rare. EGC was in close contact with other cells in their vicinity. These findings suggest that EGC is well-situated to exert influence on intestinal motility and immune functions through mechanical contraction and chemical secretion.

Men who have sex with men (MSM) are at a high risk of HIV infection and should be offered effective preventive measures, such as pre-exposure prophylaxis (PrEP). However, PrEP uptake among eligible MSM was not as high as desired. Diverse research findings on how risky sexual behaviors affect PrEP uptake highlight the necessity for a comprehensive investigation. Understanding the interconnectedness of different sexual behaviors is crucial for evaluating their impact on PrEP uptake among eligible MSM.Using a proportional sampling method, we recruited 5877 MSM aged 16 years and above in mainland China according to PrEP eligibility criteria. Through latent class analysis (LCA), three distinct sexual behavior patterns were identified among eligible MSM. Demographic variances and PrEP uptake among the three distinct sexual behavior patterns were examined using chi-squared tests and multinomial logistic regression.LCA revealed three patterns: low-risk (4,815 MSM), medium-risk (516 MSM), and high-risk (546 MSM). MSM aged 25 years or older with a monthly income of ≥¥8,000 were more likely to be in the medium-risk group. Those from areas with high HIV prevalence and engaging as ''top'' in anal sex were more likely to be in the medium- and high-risk groups. The medium- and high-risk groups had a higher willingness, uptake, and adherence rates for PrEP than the low-risk group.LCA is effective in identifying diverse sexual behavior patterns among MSM, aiding targeted interventions to enhance PrEP uptake. Addressing demographic variations and tailoring interventions for specific risk groups are crucial for promoting PrEP dissemination and reducing HIV infection risk in eligible MSM.

To build a comprehensive framework for virtual power plant (VPP) development aligned with market dynamics and to devise effective strategies to foster its growth, this study undertakes several key steps. Firstly, it constructs a VPP development framework based on market conditions, to drive the evolution of new power systems and facilitating energy transformation. Secondly, through a blend of theoretical analysis and model construction, the fundamental principles of VPP are systematically elucidated, and a decision model for the VPP development framework, focusing on price demand response, is formulated. Lastly, an optimal scheduling model for the new power system is developed, with its efficacy validated across three distinct scenarios. The findings underscore the critical importance of integrating energy storage technologies, particularly pumped storage hydropower systems, for achieving balance and optimization within new power systems. Model verification reveals that the incorporation of energy storage power stations significantly enhances system stability and efficiency, particularly in addressing the volatility associated with renewable energy sources. Additionally, the analysis indicates that while the adoption of energy storage technologies may marginally increase overall power generation costs, the total power generation cost declines with the integration of battery storage and pumped storage hydropower stations. This suggests that leveraging energy storage technologies not only enhances system operational reliability but also contributes to reducing the overall cost of power production to a certain extent. In summary, this study presents an economic and environmentally sustainable scheduling model for new power systems within the context of market trading environments. By offering both theoretical insights and practical guidance, it aims to support sustainable development and energy transformation initiatives. Ultimately, the study is poised to foster the adoption of clean energy, facilitate the establishment of smart grids, and bolster the sustainable utilization of energy resources, thereby advancing environmental conservation efforts.

Background: Primary malignant bone cancers have extremely low incidence, resulting in poor evaluation of their epidemiological characteristics. The objective of this study was to investigate trends in the incidence of primary malignant bone cancers and related mortality. Materials and methods: Data from patients diagnosed with malignant bone cancers from 2000 to 2017 in the Surveillance Epidemiology and End Results database were retrospectively analyzed. Annual age-adjusted incidence and mortality were calculated, and the annual percentage change analyzed. Further, characteristics including patient age and sex, as well as the primary site and stage of different tumor types, were analyzed. Results: The overall age-adjusted incidence rate of primary malignant bone cancers was 7.70 per million people per year, and incidence rates had increased in patients between 60 and 79 years old, or with tumor size ≥ 8 cm. The incidence of chordoma increased significantly (annual percentage change (APC), 3.0 % per year), while those of WHO grade I and II primary bone cancers decreased. During 2000–2017, the mortality rate attributable to malignant bone cancers across the entire United States was 4.41 per million people per year. A positive mortality trend was observed during the study period (APC = 0.7 %, 95 % confidence interval: 0.0 %–1.5 %). Patients with osteosarcoma, and those who were female or of white ethnicity showed significant increasing trends in mortality rate. Conclusions: Different tumor types have variable epidemiological manifestations, in terms of incidence and mortality, and exhibited altered trends over recent years. These variables can provide guidance to inform allocation of medical resources.

Elastomeric polyurethane (EPU) is characterised by distinctive mechanical properties, including high toughness, low glass transition temperature, and high impact resistance, that render it indispensable in diverse engineering applications from soft robotics to anti-collision devices. This study presents a thermo-mechanically coupled constitutive model for EPU, systematically incorporating hyperelasticity, viscoelasticity, thermal expansion, and self-heating effect in a thermodynamically consistent manner. Experimental data, obtained from previous studies, are then used for parameter identification and model validation, including iterative updates for temperature parameters considering the self-heating effect. Subsequently, the validated model is integrated into finite element codes, i.e., user subroutine to define a material’s mechanical behaviour (UMAT) based on the commercial finite element software ABAQUS, for the computation of three-dimensional stress-strain states, facilitating the analysis of the structural response to various mechanical loads and boundary conditions. The results obtained from simulations are compared with analytical solutions to confirm the precision of Finite Element Method (FEM) implementation. The self-heating effect is further analysed under different strain rates and temperatures. To validate the engineering significance of the FEM implementation, a plate with a hole structure is also simulated. In conclusion, this research provides a robust tool for engineers and researchers working with soft materials, enhancing their understanding and predictive capabilities, notably addressing the self-heating effect in thermo-mechanical behaviours.

Silicosis is a disease characterized by lung inflammation and fibrosis caused by long-term inhalation of free silicon dioxide (SiO2). Recent studies have found that a large number of lymphatic hyperplasia occurs during the occurrence and development of silicosis. miRNAs play an important role in lymphangiogenesis. However, the regulation and mechanism of miRNAs on lymphangiogenesis in silicosis remain unclear. In this study, lymphangiogenesis was observed in silicosis rats, and VEGF-C-targeted miRNAs were screened, and the effect of miRNAs on the formation of human lymphatic endothelial cells (HLECs) tubular structure was investigated in vitro. The results showed that SiO2 promoted the expressions of Collagen Ι and α-SMA, TNF-α, IL-6 and VEGF-C increased first and then decreased, and promoted the formation of lymphatic vessels. Bioinformatics methods screened miR-455–3p for targeted binding to VEGF-C, and dual luciferase reporter genes confirmed VEGF-C as the target gene of miR-455–3p, and miR-455–3p was down-regulated in the lung tissue of silicosis rats. Transfection of miR-455–3p Inhibitors down-regulated the expression level of miR-455–3p and up-regulated the expression levels of VEGF-C and VEGFR-3 in HLECs, enhanced migration ability and increased tube formation. Transfection of miR-455–3p Mimics showed an opposite trend. These results suggest that miR-455–3p further regulates the tubular structure formation of HLECs by regulating VEGF-C/VEGFR3. Therefore, targeting miR-455–3p may provide a new therapeutic strategy for SiO2-induced silicosis injury.

Using first-principles calculations, we have systematically studied thermodynamic stability, electronic structure and mechanical properties of Mo-Re binary alloys. The alloying element Re prefers to occupy the substitution position with a formation energy of 0.10 eV in Mo rather than the tetrahedron/octahedron interstitial position. The charge transfers are obviously present between Re and Mo atoms, which can be confirmed by the Bader charge analysis. The density of states (DOS) demonstrates that the d orbitals of Re and Mo atoms are hybridized, revealing that Re and its adjacent Mo atoms can form the directional bond containing covalent components. On the basis of above studies on the most stable occupancy structure, the mechanical quantities (the elastic constants Cij, bulk modulus B, Young’s modulus E, shear modulus G, Poisson’s ratio v, and B/G) have been analyzed for three Mo-Re alloys with the low Re content, which are Mo127Re1, Mo53Re1 and Mo15Re1, respectively. All these mechanical quantities of both Mo127Re1 and Mo53Re1 alloys are nearly the same as that of perfect Mo, while all these mechanical quantities of Mo15Re1 alloy are obviously larger or smaller than that of perfect Mo. This demonstrates that Mo15Re1 alloy has significantly different mechanical characteristics from Mo127Re1 and Mo53Re1 alloys as well as perfect Mo. These results can provide a significant reference for the application of Mo-Re alloys in future fusion fields.

Amid an era of rapid globalization and technological advancement, translation technologies stand as valuable assets for college students to enhance accuracy and efficiency in the translation process. However, the adoption and acceptance of these technologies are contingent on several psychological factors, which are underexplored in the academic field. This study, populated by a cohort of 397 college students, employs a multiple-item questionnaire measuring computer self-efficacy, learning motivation, cognitive engagement, and the behavioral intention to utilize translation technologies. The collected data were analyzed through a Partial Least Squares-Structural Equation Modeling (PLS-SEM) approach. Results indicated that computer self-efficacy significantly correlated with learning motivation, cognitive engagement, and behavioral intention to use translation technologies. Learning motivation and cognitive engagement were identified as critical mediators; combined, they exhibited a chain mediating effect on the association between computer self-efficacy and the intention to adopt translation technologies. Untangling the intertwined influences of these psychological constructs provides profound implications for the stakeholders, including tertiary education institutions, educators, curriculum developers, and technologists, to design effective pedagogical strategies and technology platforms to enhance translation technology adoption. This will equip students to harness these technologies and create a conducive environment for them to thrive in a globalized and digitally interconnected world.

Background: Cepharanthine (CEP), a natural bis-benzylisoquinoline alkaloid extracted from the plant Stephania cephalantha Hayata, has been widely used to treat several acute and chronic diseases. However, its antiviral potential against influenza A virus (IAV) infection remains unknown. Purpose: The study aims to assess the antiviral and immunomodulatory effects of CEP in vivo and in vitro and investigate its underlying antiviral mechanisms. Methods: Antiviral and anti-inflammatory activities of CEP were assessed in MDCK, A549 and RAW264.7 cells infected with influenza virus. Proinflammatory cytokine levels were measured by qRT-PCR and ELISA. The anti-influenza effect and underlying antiviral mechanism of CEP were mainly determined by MTT assay, plaque reduction assay, time-of-addition and mini-replicon assay. The inhibition of CEP on IAV-induced activation of innate immune signaling was detected by western blotting. Furthermore, BALB/c mice were infected intranasally with A/PR/8/34 (H1N1) virus and treated with CEP (60, 30, 15 mg/kg/d) or oseltamivir (60 mg/kg/d). The changes in body weight, survival rates, viral titers, proinflammatory cytokine levels and pathological parameters were detected. Results: CEP exhibited antiviral effects against multiple IAV strains, while also demonstrating anti-inflammatory effects in influenza virus-infected RAW264.7 and A549 cells. The results of the mechanism study indicated that CEP effectively suppressed IAV replication by limiting viral polymerase activity. On the other hand, CEP could modulate pro-inflammatory responses via inhibition of janus kinase/signal transducer and activator of transcription/ nuclear factor kappa B (JAK/STAT/NF‑κB) signaling pathways involved in influenza virus pathogenesis. Treatment of mice with CEP improved the survival rate and body weight of influenza virus-infected mice, reduced viral titers and alleviated influenza virus-induced pathological damage and inflammation in mouse lung tissue. Conclusion: Collectively, the anti-influenza virus property of CEP was a result of inhibiting viral polymerase activity and preventing virus-induced excessive inflammation, highlighting it might be an oral medication for the treatment of IAV infection.

Background: The major facilitator superfamily glucose transporters (GLUTs), encoded by solute carrier 2A (SLC2A) genes, mediate the transmembrane movement and uptake of glucose. To satisfy the improved energy demands, glycolysis flux is increased in cancers compared with healthy tissues. Multiple diseases, including cancer, have been associated with GLUTs. Nevertheless, not much research has been done on the functions of SLC2As in pan-cancer prognosis or their clinical treatment potential. Methods: The SLC2A family genes' level of expression and prognostic values were analyzed in relation to pan-cancer. We then examined the association among SLC2As expression and TME, Stemness score, clinical characteristics, immune subtypes, and drug sensitivity. We merged bioinformatics analysis techniques with up-to-date public databases. Additionally, SLC2As from the KOBAS database were subjected to enrichment analysis. Results: We discovered that SLC2As' gene expression differed significantly between normal tissues and many malignancies. A number of tumors from various databases demonstrate a relationship between prognosis and SLC2A family gene expression. For instance, SLC2A2 and SLC2A5 were associated with the overall survival (OS) of hepatocellular carcinoma. SLC2A1 was associated with the OS of lung adenocarcinoma and pancreatic adenocarcinoma. Moreover, the SLC2A family gene expression is significantly correlated with the pan-cancer stromal and immune scores, and the RNA and DNA stemness scores. Furthermore, we found that the majority of SLC2As had a strong correlation with the tumor stages in KIRC. The immunological subtypes and all members of the SLC2A gene family exhibited a substantial correlation. Moreover, pathways containing insulin resistance and adipocytokine signaling pathway may influence the progression of some cancers. Finally, there is a significant positive or negative connection between drug sensitivity and SLC2A1 expression. Conclusion: Our research highlights the significant promise of SLC2As as prognostic indicators and offers insightful approaches for upcoming exploration of SLC2As as putative therapeutic targets in malignancies.

The exploration of high-performance, durable and cost-effective catalysts for overall water splitting, including the hydrogen evolution reaction (HER) and the oxygen evolution reaction (OER), has always been a vibrant topic in electrochemical water splitting techniques. Here we report a facile strategy for the synthesis of antiperovskite bimetallic nitrides (FeNNi3 and CuNNi3) and their NiFe-MOF morphology on nickel foams (NF) for HER and OER respectively in alkaline media. The NiFe-MOF and FeNNi3 nanoparticle exhibit strong coupling and synergistic effects, resulting in a solid integrated structure and fast electron transfer. The FeNNi3 towards HER shows an overpotential of 57 mV at 10 mA cm−2 in alkaline media, and its MOF morphology shows a low overpotential of 219 mV at 10 mA cm−2 towards OER. The alkaline electrolyzer of FeNNi3/NF || NiFe-MOF@FeNNi3/NF for overall water splitting demonstrates a low cell voltage of 1.49 V at 10 mA cm−2 with high cycling durability. This work investigates antiperovskite nitrides' capabilities for overall water splitting and provides guidance on designing high-performance catalytic materials.

Accurate prediction of mineral resources is imperative to meet the energy demands of modern society. Nonetheless, this task is often difficult due to estimation bias and limited interpretability of conventional statistical techniques and machine learning methods. To address these shortcomings, we propose a novel geospatial artificial intelligence approach, denoted as geographically neural network-weighted logistic regression, for mineral prospectivity mapping. This model integrates spatial patterns and neural networks, combined with the Shapley additive explanations theory to achieve accurate forecasts and provide explainable insight into mineralization within intricate spatial contexts. In a gold prospecting experiment conducted in Nova Scotia, our model outperformed other state-of-the-art models with a 5% to 16% increase in the area under the receiver operating characteristic curve metric. The presented framework further provided intuitive quantifications of the impact of geological factors on the gold mineralization in spatial settings. The innovative approach promotes novel phenomenon detection and exhibits robust capabilities and universality for classification problems within complex spatial scenarios.

Background: The glucose derivative 3-O-methyl-D-glucose (OMG) is used as a cryoprotectant in freezing cells. However, its protective role and the related mechanism in static cold storage (CS) of organs are unknown. The present study aimed to investigate the effect of OMG on cod ischemia damage in cold preservation of donor kidney. Methods: Pretreatment of OMG on kidney was performed in an isolated renal cold storage model in rats. LDH activity in renal efflux was used to evaluate the cellular damage. Indicators including iron levels, mitochondrial damage, MDA level, and cellular apoptosis were measured. Kidney quality was assessed via a kidney transplantation (KTx) model in rats. The grafted animals were followed up for 7 days. Ischemia reperfusion (I/R) injury and inflammatory response were assessed by biochemical and histological analyses. Results: OMG pretreatment alleviated prolonged CS-induced renal damage as evidenced by reduced LDH activities and tubular apoptosis. Kidney with pCS has significantly increased iron, MDA, and TUNEL+ cells, implying the increased ferroptosis, which has been partly inhibited by OMG. OMG pretreatment has improved the renal function (p

Summary: Background: Hospitals in China are classified into tiers (1, 2 or 3), with the largest (tier 3) having more equipment and specialist staff. Differential health insurance cost-sharing by hospital tier (lower deductibles and higher reimbursement rates in lower tiers) was introduced to reduce overcrowding in higher tier hospitals, promote use of lower tier hospitals, and limit escalating healthcare costs. However, little is known about the effects of differential cost-sharing in health insurance schemes on choice of hospital tiers. Methods: In a 9-year follow-up of a prospective study of 0.5 M adults from 10 areas in China, we examined the associations between differential health insurance cost-sharing and choice of hospital tiers for patients with a first hospitalisation for stroke or ischaemic heart disease (IHD) in 2009–2017. Analyses were performed separately in urban areas (stroke: n = 20,302; IHD: n = 19,283) and rural areas (stroke: n = 21,130; IHD: n = 17,890), using conditional logit models and adjusting for individual socioeconomic and health characteristics. Findings: About 64–68% of stroke and IHD cases in urban areas and 27–29% in rural areas chose tier 3 hospitals. In urban areas, higher reimbursement rates in each tier and lower tier 3 deductibles were associated with a greater likelihood of choosing their respective hospital tiers. In rural areas, the effects of cost-sharing were modest, suggesting a greater contribution of other factors. Higher socioeconomic status and greater disease severity were associated with a greater likelihood of seeking care in higher tier hospitals in urban and rural areas. Interpretation: Patient choice of hospital tiers for treatment of stroke and IHD in China was influenced by differential cost-sharing in urban areas, but not in rural areas. Further strategies are required to incentivise appropriate health seeking behaviour and promote more efficient hospital use. Funding: Wellcome Trust, Medical Research Council, British Heart Foundation, Cancer Research UK, Kadoorie Charitable Foundation, China Ministry of Science and Technology, and National Natural Science Foundation of China.

Vascular diseases, a leading cause of death in human, are strongly associated with pathological damage to blood vessels. The selenoprotein (Sel) have been reported to play important roles in vascular disease. However, the role of SelO in vascular disease has not been conclusively investigated. The present experiment was to investigate the regulatory mechanism of the effect of SelO on the permeability of vascular endothelial. The H.E staining, FITC-Dextran staining, Dil-AC-LDL staining and FITC-WGA staining showed that vascular structure was damaged, and intercellular junctions were disrupted with selenium (Se)-deficient. Immunohistochemistry, qPCR and Western blot revealed decreased expression of the adhesion plaque proteins vinculin, talin and paxillin, decreased expression of the vascular connectivity effector molecules connexin, claudin-1 and E-cadherin and increased expression of JAM-A and N-cadherin, as well as decreased expression of the ZO-1 signaling pathways ZO-1, Rock, rhoGEF, cingulin and MLC-2. In a screening of 24 Sel present in mice, SelO showed the most pronounced changes in vascular tissues, and a possible association between SelO and vascular intercellular junction effectors was determined using IBM SPSS Statistics 25. Silencing of SelO, vascular endothelial intercellular junction adverse effects present. The regulatory relationship between SelO and vascular endothelial intercellular junctions was determined. The results showed that Se deficiency lead to increased vascular endothelial permeability and vascular tissue damage by decreasing SelO expression, suggesting a possible role for SelO in regulating vascular endothelial permeability.

Micro- and nano-plastics (MNPs) pollution has become a pressing global environmental issue, with growing concerns regarding its impact on human health. However, evidence on the effects of MNPs on human health remains limited. This paper reviews the three routes of human exposure to MNPs, which include ingestion, inhalation, and dermal contact. It further discusses the potential routes of translocation of MNPs in human lungs, intestines, and skin, analyses the potential impact of MNPs on the homeostasis of human organ systems, and provides an outlook on future research priorities for MNPs in human health. There is growing evidence that MNPs are present in human tissues or fluids. Lab studies, including in vivo animal models and in vitro human-derived cell cultures, revealed that MNPs exposure could negatively affect human health. MNPs exposure could cause oxidative stress, cytotoxicity, disruption of internal barriers like the intestinal, the air–blood and the placental barrier, tissue damage, as well as immune homeostasis imbalance, endocrine disruption, and reproductive and developmental toxicity. Limitedly available epidemiological studies suggest that disorders like lung nodules, asthma, and blood thrombus might be caused or exacerbated by MNPs exposure. However, direct evidence for the effects of MNPs on human health is still scarce, and future research in this area is needed to provide quantitative support for assessing the risk of MNPs to human health.

Objective: The study objective was to evaluate the midterm outcome of thoracic endovascular aortic repair compared with open repair in patients with descending thoracic aortic aneurysm. Methods: From August 1993 to February 2023, 499 patients with descending thoracic aortic aneurysms underwent open repair (n = 221) or thoracic endovascular aortic repair (n = 278). Of these, 120 matched pairs were identified using propensity score matching based on age, sex, chronic lung disease, stroke, coronary artery disease, diabetes, ejection fraction, dialysis, peripheral vascular disease, prior cardiac surgery, connective tissue disease, and chronic dissection. Primary outcomes were postoperative paralysis, operative mortality, reoperation, and midterm survival. Results: After matching, the preoperative demographics and comorbidities were balanced in both groups. Intraoperatively, open repair had a lower temperature (18 °C vs 36 °C) and more patients required blood products (66% vs 8%), P

This study aims to investigate the anisotropic fracture toughness of an α+β titanium alloy processed by β forging. A typical basket-weave microstructure is observed, including the primary α (αp) phase, micron-scaled secondary α (αs) phase and residual β phase. The tensile test results show that the anisotropic strength results from the fine grain strengthening as well as the texture strengthening, and the plasticity difference is determined by the normal stress acting on the main crack in the fracture process. The orientation of the specimen also has a significant impact on fracture toughness. The corresponding toughening models of underlying damage mechanism with different orientations are proposed and discussed. It is found that the internal toughening mechanism is dominant, and external toughening mechanism also plays an important role in fracture toughness, including delamination and crack deflection caused by elongated β grains arrangement. Finally, the differences of J-integral resistance curves with different orientations are investigated in detail. The strength and fracture toughness values, KJIC (crack-initiation toughness) and KSS (growth toughness), are both highest when loading along radial direction (RD), and the positive effects of β grain morphology and two-phase texture on anisotropy of KJIC are summarized.

Fatty acids (FAs), which were initially recognized as energy sources and essential building blocks of biomembranes, serve as the precursors of important signaling molecules. Tracing FA metabolism is essential to understanding the biochemical activity and role of FAs in physiological and pathological events. Inspired by the advances in click chemistry for protein enrichment, we herein established a click chemistry-based enrichment (CCBE) strategy for tracing the cellular metabolism of eicosapentaenoic acid (EPA, 20:5 n-3) in neural cells. Terminal alkyne-labeled EPA (EPAA) used as a surrogate was incubated with N2a, mouse neuroblastoma cells, and alkyne-labeled metabolites (ALMs) were selectively captured by an azide-modified resin via a Cu(I)-catalyzed azide-alkyne cycloaddition reaction for enrichment. After removing unlabeled metabolites, ALMs containing a triazole moiety were cleaved from solid-phase resins and subjected to liquid chromatography mass spectrometry (LC-MS) analysis. The proposed CCBE strategy is highly selective for capturing and enriching alkyne-labeled metabolites from the complicated matrices. In addition, this method can overcome current detection limits by enhancing MS sensitivity of targets, improving the chromatographic separation of sn-position glycerophospholipid regioisomers, facilitating structural characterization of ALMs by a specific MS/MS fragmentation signature, and providing versatile fluorescence detection of ALMs for cellular distribution. This CCBE strategy might be expanded to trace the metabolism of other FAs, small molecules, or drugs.

Background/purpose: Epigallocatechin-3-gallate (EGCG) is playing an increasingly important role in the treatment of oral diseases. However, its mechanisms remain to be clarified. This study aimed to investigate the effect of EGCG on oxidative and inflammatory stress and bone loss in experimental periodontitis. Materials and methods: Periodontitis was induced in rats, followed by gavage using different concentrations of EGCG for 5 weeks. The levels of interleukin-1β (IL-1β), interleukin-18 (IL-18), tumor necrosis factor-α (TNF-α), superoxide dismutase (SOD) and malondialdehyde (MDA) in rats were measured. The degree of alveolar bone loss and the number of inflammatory cells were detected. The integrated optical density of nuclear factor erythroid 2-related factor (Nrf2), heme oxygenase-1 (HO-1), NLR pyrin domain-containing 3 (NLRP3) and nuclear factor-kappaB p65 (NF-κB p65) was measured. Results: EGCG (200 mg/kg) significantly reduced alveolar bone loss in the ligated maxillary molars and the number of inflammatory cells in the EGCG-200 group compared with the periodontitis, EGCG-100 and EGCG-400 groups. 200 mg/kg was the optimal dose of EGCG and was used in subsequent experiments. The expression levels of IL-1β, IL-18, TNF-α and MDA were significantly lower and the expression level of SOD was significantly higher in the EGCG-200 group compared with the periodontitis group. The expression of NLRP3 and NF-κB p65 was significantly decreased, while the expression of Nrf2 and HO-1 was significantly increased in the EGCG-200 group compared with the periodontitis group. Conclusion: These results suggest that EGCG inhibits oxidative stress and inflammatory responses in the periodontitis model by modulating the Nrf2/HO-1/NLRP3/NF-κB p65 signaling pathway, thereby decreasing alveolar bone loss.

Ecological welfare performance (EWP) is an important indicator for assessing the sustainable development potential of an area. Despite the progress made in understanding EWP in the Yangtze River Economic Belt (YREB), there still needs to be a research gap in studying its spatial variability in depth, which is more critical for improving EWP in the region and promoting the dynamic management of urban ecological This study addresses this gap by focusing on the YREB. Our investigation not only aims to measure the EWP of the YREB but also delves into analyzing its spatial distribution characteristics and modeling spatial variability. Motivated by the necessity to comprehend the welfare status of urban EWP in the YREB, our research contributes to urban ecological resource management and informs decisions for sustainable development. Results found: (1) EWP in the YREB has improved by 16.81%, exhibiting a southwest to northeast distribution with downstream gravitational movement. (2) A gradual reduction in EWP scope is accompanied by increased spatial dependence and resulting structural variation. Geographically, EWP displays a polar core and banding distribution, with high-value areas converging in upstream and downstream cities of the YREB. (3) The semi-variance function fits the model better, showing that the spatial variability of the ecological welfare performance of cities in the YREB is dominated by structural variability. This study has the potential to broaden the research focus on the spatial characterization of EWP and offers valuable insights into the management of urban ecological resources in the YREB. The perspective of welfare enhancement adds a crucial dimension to our understanding, providing practical lessons for effective resource management.

In this study, we systematically investigated the emulsifying capabilities of myofibrillar protein (MP)- and MP peptide (MPP)-based conjugates synthesized through intensification techniques: water bath (WB), microwave, ultrasound, and the combined ultrasound-microwave (UM) methods. Compared with WB, microwave, and ultrasound treatments, the combined UM treatment greatly promoted the glycation reaction because ultrasound and microwave mutually reinforced modification effects. The resultant conjugate structure tended to unfold with more flexible conformation and homogeneous morphology. Moreover, the emulsifying properties of conjugates developed with single and combined ultrasound-assisted glycation displayed substantial improvement, and pre-hydrolysis further enhanced these performances, as observed in the Principal Component Analysis as well. Remarkably, MPP grafted by maltodextrin with the assistance of a combined UM field produced the smallest and most uniform emulsion system, positioning it as the most efficient emulsifier among all the fabricated glycoconjugates. Our study highlighted the potential of synergistically applying ultrasound and microwave techniques to develop a well-performance glycation with an ideal conjugate structure, in which they would be associated into a strong film that provided the robust physical barrier, creaming stability, heat retention, and oxidation resistance. These findings offered a basis for better utilizing complex ultrasonic technology to develop novel and improved MP-based food products.

The limitations of current drug-eluting stent technologies in selectively inhibiting vascular smooth muscle cell proliferation, which often leads to inflammation, call for innovative approaches in coronary artery disease treatment. In the present work, we propose a revolutionary solution: a three-in-one platform for vascular stents, combining arsenic trioxide (ATO) and tacrolimus (TAC) to address anti-proliferation, pro-endothelialization, and anti-inflammation aspects. Our findings demonstrate that the synergistic action of ATO and TAC effectively suppresses aberrant vascular smooth muscle cell proliferation and mitigates endothelial cell inflammation. Remarkably, the combination treatment of TAC/ATO enhances endothelial cell migration and adhesion abilities. Moreover, our TAC/ATO-eluting stent exhibits superior re-endothelialization and anti-restenosis effects in a rabbit and porcine stent implantation model. Both in vitro and in vivo results solidify the notion that the TAC/ATO-eluting stent ensures rapid re-endothelialization and significantly reduces the incidence of in-stent restenosis. Overall, this study represents a promising and novel multifunctional platform with immense potential in the therapy of coronary artery disease.

The chemical recycling of polyolefin presents a considerable challenge, especially as upcycling methods struggle with the reality that plastic wastes typically consist of mixtures of polyethylene (PE), polystyrene (PS), and polypropylene (PP). We report a catalytic aerobic oxidative approach for polyolefins upcycling with the corresponding carboxylic acids as the product. This method encompasses three key innovations. First, it operates under atmospheric pressure and mild conditions, using O2 or air as the oxidant. Second, it is compatible with high-density polyethylene, low-density polyethylene, PS, PP, and their blends. Third, it uses an economical and recoverable metal catalyst. It has been demonstrated that this approach can efficiently degrade mixed wastes of plastic bags, bottles, masks, and foam boxes.

This study investigated the grafting chlorogenic acid (CA) onto myosin, utilizing various techniques including conventional method, ultrasound, microwave, and combination of ultrasound and microwave (UM). The grafting efficiency was as follows: conventional method

Summary: Background: Previous observational studies established a positive relationship between snoring and stroke. We aimed to investigate the causal effect of snoring on stroke. Methods: Based on 82,339 unrelated individuals with qualified genotyping data of Asian descent from the China Kadoorie Biobank (CKB), we conducted a Mendelian randomization (MR) analysis of snoring and stroke. Genetic variants identified in the genome-wide association analysis (GWAS) of snoring in CKB and UK Biobank (UKB) were selected for constructing genetic risk scores (GRS). A two-stage method was applied to estimate the associations of the genetically predicted snoring with stroke and its subtypes. Besides, MR analysis among the non-obese group (body mass index, BMI

Recent studies revealed that the greening in China has difficulty crossing the Hu-Line. However, the greening pattern and its driving factors remain unclear. Therefore, we explored NDVI spatio-temporal pattern and their key driving forces between southeastern and northwestern of the Hu-line from 2000 to 2020 using GDM (the geographical detector model) and trend analysis method. The following results were obtained: (1) Overall, NDVI showed a fluctuating upward trend in China over the study period, indicating greening. Although vegetation had improved significantly (48.11%) on the southeastern region of the Hu-line, it had significantly degraded (24.71%) on the northwestern region. The degradation of vegetation cover on unused and construction land was larger than the proportion of improvement. (2) GDM could identify the effect of single-factors on the NDVI variables on both side regions of the Hu-line. P (precipitation), POP (population density), and DEM (Digital Elevation), dominated NDVI’s spatial pattern in China. ET (evapotranspiration), ST (soil types) and POP had the strongest influence on the southeastern region, whereas P was the dominant factor on the northwestern region. In addition, POP, GDP (gross domestic product) and TEM (temperature) dominated the overall trend of NDVI. (3) Seven factors influenced and verged vegetation NDVI spatial distribution and change trends of vegetation were enhanced by their interaction. Overall, China is becoming greener. For various land-use types, natural factors (such as P and DEM) dominated vegetation NDVI pattern. Nevertheless, anthropogenic factors governed NDVI pattern of construction land. Anthropogenic factors mainly controlled NDVI tendency variations. The findings could effectively explain greening on both side regions of the Hu-line, and provide information for decision-making on vegetation restoration and ecological protection.