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The thermal problems closely related to the development of human life, scientific technology and engineering production are greatly influenced by the thermal properties of carrier media, while most traditional natural substances are incompetent to achieve the flexible and diverse on-demand thermal control that is increasingly needed. Stimulated by materials science and physics, the combination of thermal metamaterial (artificial composite with peculiar thermalphyscial properties) and transformation thermotics (theoretical method of pre-designing heat distribution at will) has promoted heat transfer research enter a novel phase. Aiming at macroscopic heat transfer that is one of the most fundamental cases in thermal science and directly affects various thermal management and thermal rectification problems, in this review, we retrace the progress of transformed thermal meta-devices for manipulating macroscopic thermal field from the various aspects combining theoretical calculation, numerical simulation and experimental verification. Apart from the devices containing single field manipulation function or applicable to single thermal field, we further take a look at multifunctional transformed thermal meta-devices including devices that suitable for different physical fields and containing various forms of thermal field manipulation. Moreover, we review the explorations of practical application of transformed thermal meta-devices. Finally, we point out some limitations and challenges together with potential future directions in this fascinating area.

Background & Aims: The machinery that prevents colorectal cancer liver metastasis (CRLM) in the context of liver regeneration (LR) remains elusive. Ceramide (CER) is a potent anti-cancer lipid involved in intercellular interaction. Here, we investigated the role of CER metabolism in mediating the interaction between hepatocytes and metastatic colorectal cancer (CRC) cells to regulate CRLM in the context of LR. Methods: Mice were intrasplenically injected with CRC cells. LR was induced by 2/3 partial hepatectomy (PH) to mimic the CRLM in the context of LR. The alteration of corresponding CER-metabolizing genes was examined. The biological roles of CER metabolism in vitro and in vivo were examined by performing a series of functional experiments. Results: Induction of LR augmented apoptosis but promoted matrix metalloproteinase 2 (MMP2) expression and epithelial-mesenchymal transition (EMT) to increase the invasiveness of metastatic CRC cells, resulting in aggressive CRLM. Up-regulation of sphingomyelin phosphodiesterase 3 (SMPD3) was determined in the regenerating hepatocytes after LR induction and persisted in the CRLM-adjacent hepatocytes after CRLM formation. Hepatic Smpd3 knockdown was found to further promote CRLM in the context of LR by abolishing mitochondrial apoptosis and augmenting the invasiveness in metastatic CRC cells by up-regulating MMP2 and EMT through promoting the nuclear translocation of β-catenin. Mechanistically, we found that hepatic SMPD3 controlled the generation of exosomal CER in the regenerating hepatocytes and the CRLM-adjacent hepatocytes. The SMPD3-produced exosomal CER critically conducted the intercellular transfer of CER from the hepatocytes to metastatic CRC cells and impeded CRLM by inducing mitochondrial apoptosis and restricting the invasiveness in metastatic CRC cells. The administration of nanoliposomal CER was found to suppress CRLM in the context of LR substantially. Conclusions: SMPD3-produced exosomal CER constitutes a critical anti-CRLM mechanism in LR to impede CRLM, offering the promise of using CER as a therapeutic agent to prevent the recurrence of CRLM after PH.

Recently, rapid development of intelligent wearable electronic equipment has triggered great needs for flexible and lightweight portable energy storage systems. Here, we demonstrate a low-cost ($ 0.5 m-2) and low density carbonized facial tissue paper (FCP) for high-conductive NiCo2S4 nanotubes assisted novel ultra-flexible solid-state supercapacitors (SSCs). The hydrothermal synthesized FCP-900@NiCo2S4 electrodes in this paper only have a density of 5 mg cm−2 and show large specific capacitance of 3115 mF cm−2 at 2 mA cm−2. Based on the high performance of FCP-900@NiCo2S4 electrodes, the as assembled SSCs can deliver an energy density of 1.2 mWh cm−3, high power density of 58.16 mW cm−3. It also shows great bending-state capacitive performance with high capacitance retention after 5000 cycles, providing a new opportunity for developing high-performance flexible wearable energy storage devices.

Microbubbles have captured the attention of scholars due to their exceptional physical and chemical properties that exhibit practical applications. Transcranial Doppler ultrasound is a diagnostic tool used in clinical medicine to identify patent foramen ovale (PFO) heart disease caused by incomplete fusion of primary and secondary septum after birth, using microbubbles. The volume of gas and size of the bubbles determine the consequences of air entering the bloodstream. Therefore, it is imperative to investigate stable and efficient microbubble generation technology. The team designed and developed a new type of bubble generator and performed basic research on the flow and mixing rules in the gas-liquid two-phase system in the syringe. The shadow imaging method was used to explore the influence of the equipment operation parameters on the experimental system's microbubble flow process. After analyzing multiple sets of experimental data, it was found that the diameter of bubbles decreases as the frequency increases. After ten times of high-frequency reciprocating movement of the equipment, the microbubble size distribution is mainly between 10–100 μm, the mean diameter is between 23–26 μm, and the relative standard deviation is less than 4.5 %. Compared to manual methods, the device exhibits good accuracy and repeatability.

Objectives: Ultrasound Needle, which is an improved ultrasonic horn device, has shown great potential for promoting the diffusion of thrombolytic drugs within clots and enhancing clot lysis efficiency. However, the clot lysis efficiency of different thrombolytic drugs with the synergy of Ultrasound Needle remains unknown. In this study, we aimed to compare the lysis efficiency of the non-fibrin-specific drug urokinase and fibrin-specific drug reteplase with the synergy of Ultrasound Needle. Materials and methods: Twenty-five milliliters of human blood was incubated for 1.5 h to form in vitro clots and then received the corresponding treatment protocols: control group (normal saline), US group (10 min of Ultrasound Needle treatment), UK group (30000IU of urokinase), r-PA group (2 mg of reteplase), US + UK group, and US + r-PA group. After treatment, the morphological changes of the clots were analyzed by B-mode ultrasound imaging and hematoxylin and eosin (H&E) staining. Lysis efficiency was evaluated based on the relative end weight (final weight/initial weight). The fibrin density of the different groups after treatment was assessed by immunofluorescence staining. Results: Morphological examination and relative end weight analysis showed that combination therapies induced a more thorough dissolution of clots compared with single therapies, and the US + r-PA group exhibited higher lysis efficiency than the US + UK group. In addition, immunofluorescence staining showed that the US + r-PA group had fewer remaining thrombus fibrins than the US + UK group after treatment. Conclusions: The Ultrasound Needle can significantly improve the clot lysis efficiency of both fibrinolytic drugs, and fibrin-specific reteplase exhibited superior lysis efficiency over non-fibrin-specific urokinase with the synergy of the Ultrasound Needle.

Central obesity has increased rapidly over the past decade and posed a substantial disease burden worldwide. Exposure to metals/metalloids has been acknowledged to be involved in the development of central obesity through regulation of cortisol, insulin resistance, and glucocorticoid receptor reduction. Despite the importance, it is lack of prospective study which comprehensively evaluate the relations between multiple metals exposure and central obesity. We explored the prospective associations of plasma metal concentrations with central obesity in a prospective study of the Dongfeng-Tongji cohort. The present study included 2127 participants with a 6.87-year mean follow-up duration. We measured 23 plasma metal/metalloid concentrations at baseline. The associations between metals and incident central obesity were examined utilizing the Cox proportional hazard regression in single and multiple metals models. Additionally, we applied elastic net (ENET), Bayesian kernel machine regression (BKMR), plasma metal score (PMS), and quantile-based g-computation (Qgcomp) models to explore the joint associations of metal mixtures with central obesity. After adjusting potential confounders, we found significant associations of plasma manganese (Mn) and thallium (Tl) concentrations with a higher risk of central obesity, whereas plasma rubidium (Rb) concentration was associated with a lower risk of central obesity both in single and multiple metals models (all FDR

Periodontitis caused by bacteria is the most common oral disease. In the face of plaque formation, traditional scaling and antibiotic treatment can lead to gum recession, drug resistance and other side effects. The nanoplatform of multifunctional complex treatment is attractive for the treatment of periodontitis. In this study, epigallocatechin gallate (EGCG) was loaded into gold nanoparticle-modified hydrogels (E-Au@H) to achieve the synergistic functions of near-infrared (NIR) photosensitization, bactericidal and periodontal tissue regeneration. E-Au@H rapidly heats up to 50.7 °C within 5 min under NIR light irradiation, exerting a good photothermal effect, while the NIR spectrum can effectively control the release of tea polyphenols, enhance the antibacterial effect, promote angiogenesis and improve bone regeneration. In vitro studies showed that NIR-irradiated composites inhibited S. aureus, E. coli and S. aureus biofilms by 94 %, 92 % and 74 %, increased alkaline phosphatase activity 5-fold after 7 days and increased extracellular matrix mineralization rate 3-fold after 21 days. The rat periodontitis model successfully demonstrated that E-Au@H with NIR light irradiation inhibited dental plaque biofilm by 87 % and promoted alveolar bone regeneration by 38 %. The experimental results suggest that this hydrogel with a NIR-sensitive composite nanoplatform offers new possibilities for the treatment of periodontal disease.

Laryngeal cancer is the most common malignant tumor for which there is still a lack of effective treatment. Traditional radiotherapy, chemotherapy, and surgery all have significant side effects. Therefore, multifunctional collaborative therapeutic nanoplatforms are attractive to patients with laryngeal cancer. In this study, a near-infrared responsive IR780-modified MXene (Ti3C2) nanosheet was proposed as a strategy for targeted therapy to achieve the synergistic functions of photothermal (PTT) therapy, photodynamic (PDT) therapy and mitochondrial pathway apoptosis. Electron spin resonance results showed that Ti3C2@IR780 could produce singlet linear oxygen for PDT. Molecular biology studies showed that Ti3C2@IR780 had the outstanding ability to generate ROS to disrupt mitochondrial function, resulting in apoptosis of cancer cells up to 60.51%. In vivo experiments showed that Ti3C2@IR780 could effectively aggregate at tumor sites. The temperature of the tumor region could reach 63.7 °C in the presence of near-infrared light. Tumor growth was inhibited by 92% during the treatment, and there was no recurrence. Results of the sections showed an 88.1% reduction in microtumor vascularity with Ti3C2@IR780 treatment for 21 days compared to the control group. These findings suggest that this multifunctional nanoplatform with synergistic NIR-sensitive properties can effectively inhibit tumor growth, providing an ideal strategy for cancer treatment.

Nasopharyngeal carcinoma (NPC) is prevalent in East and Southeast Asia. In a previous study, Epstein-Barr virus (EBV)-miR-BART22 induces tumor metastasis and stemness and is significantly involved in NPC progression. In the present study, we observed that miR-4721 is induced by EBV-miR-BART22 through phosphatidylinositol 3-kinase (PI3K)/AKT/c-JUN/Sp1 signaling to promote its transcription. In a subsequent study, we observed that miR-4721 serves as a potential oncogenic factor promoting NPC cell cycle progression and cell proliferation in vitro and in vivo. Mechanism analysis indicated that miR-4721 directly targetes GSK3β and reduces its expression, which therefore elevates β-catenin intra-nuclear aggregation and activates its downstream cell cycle factors, including CCND1 and c-MYC. In clinical samples, miR-4721 and GSK3β are respectively observed to be upregulated and downregulated in NPC progression. Elevated expression of miR-4721 is positively associated with clinical progression and poor prognosis. Our study first demonstrated that miR-4721 as an oncogene is induced by EBV-miR-BART22 via modulating PI3K/AKT/c-JUN/Sp1 signaling to target GSK3β, which thus activates the WNT/β-catenin-stimulated cell cycle signal and enhances the tumorigenic capacity in NPC. miR-4721 may be a potential biomarker or therapeutic target in NPC treatment in the future.

Background: Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-related tumor. The role of EBV-encoding miR-BART22 is still unclear in NPC. This study aimed to identify the detailed mechanisms by which EBV-miR-BART22 functions as a tumor-promoting factor and evaluate the action of cinobufotalin in treating EBV-miR-BART22-overexpressing NPC cells. Methods: Using real-time PCR, western blotting, immunohistochemistry, and In situ hybridization, we detected the expression of miR-BART22 and MAP2K4 in tissues and cells, as well as evaluated their clinical relevance in NPC patients. The effects of miR-BART22 on cell metastasis, stemness and DDP chemoresistance were examined by sphere formation assay, side population analysis, transwell, boyden, in vivo xenograft tumor mouse model et al. Western blotting, immunofluorescence staining, luciferase reporter assay, ChIP, EMSA and Co-IP assay et al. were performed to explore the detailed molecular mechanism of EBV-miR-BART22 in NPC. Finally, we estimated the effects and molecular basis of Cinobufotalin on EBV-miR-BART22-overexpressing NPC cells in vitro and in vivo assays. Findings: We observed that EBV-miR-BART22 not only promoted tumor stemness and metastasis, but also enhanced the resistance to Cisplatin (DDP) in vitro and in vivo. Mechanistic analysis indicated that EBV-miR-BART22 directly targeted the MAP2K4 and upregulated non-muscle myosin heavy chain IIA (MYH9) expression by PI3K/AKT/c-Jun-induced transcription. Further, MYH9 interacted with glycogen synthase 3β(GSK3β) protein and induced its ubiquitin degradation by activating PI3K/AKT/c-Jun-induced ubiquitin transcription and the latter combined with increased TRAF6 E3 ligase, which further bound to GSK3β protein. Reductions in the GSK3β protein thus promoted β-catenin expression and nuclear translocation, which induced tumor stemness and the epithelial-to-mesenchymal transition (EMT) signals. Furthermore, we observed that cinobufotalin, a new chemically synthesized compound, significantly suppressed EBV-miR-BART22-induced DDP chemoresistance by upregulating MAP2K4 to suppress MYH9/GSK3β/β-catenin and its downstream tumor stemness and EMT signals in NPC. Finally, clinical data revealed that increased miR-BART22 and reduced MAP2K4 expression caused the poor prognoses of NPC patients. Interpretation: Our study provides a novel mechanism that cinobufotalin reversed the DDP chemoresistance and EMT induced by EBV-miR-BART22 in NPC. Keywords: EBV-miR-BART22, Cinobufotalin, DDP chemoresistance, Stemness, NPC

Background: Exposure to metals/metalloids from both the natural environment and anthropogenic sources have a complex influence on human health. However, relatively few studies have explored the relations of exposure to multiple metals/metalloids with mortality. Therefore, this prospective study aims to examine the relations of multiple metal/metalloids exposures with all-cause and cardiovascular disease (CVD) mortality. Methods: A total of 6155 participants within the Dongfeng-Tongji (DF-TJ) cohort were involved in this analysis, which were followed for mortality until December 31, 2018. We applied inductively coupled plasma mass spectrometry (ICP-MS) to measure baseline plasma concentrations of 23 metals. We utilized Cox regression models to calculate the hazard ratios (HRs) for all-cause and CVD mortality associated with metal concentrations. We proposed plasma metal score to assess the simultaneous exposure to multiple metals through summing each metal concentration weighted by the regression coefficients with all-cause mortality. Results: During the follow-up (mean duration, 9.8 years), we ascertained 876 deaths, including 416 deaths of CVD (157 deaths of coronary heart disease and 259 deaths of stroke). In the multiple-metals model, after adjusting for potential confounders, plasma copper, molybdenum, and vanadium were positively associated with all-cause mortality, whereas manganese, selenium, and thallium were negatively associated with the risk of all-cause mortality, with adjusted HRs (95% Confidence Interval, CI) of the fourth quartiles were 1.73 (1.42–2.11, P-trend

Summary: Mechanically-gated ion channels play an important role in the human body, whereas it is challenging to design artificial mechanically-controlled ionic transport devices as the intrinsically rigidity of traditional electrodes. Here, we report on a mechanically-gated electrochemical channel by virtue of vertically aligned gold nanowires (v-AuNWs) as 3D stretchable electrodes. By surface modification with a self-assembled 1-Dodecanethiol monolayer, the v-AuNWs become hydrophobic and inaccessible to hydrated redox species (e.g., Fe(CN)63−/4− and Ru(bpy)32+). Under mechanical strains, the closely-packed v-AuNWs unzip/crack to generate ionic channels to enable redox reactions, giving rise to increases in Faradaic currents. The redox current increases with the strain level until it reaches a certain threshold value, and then decreases as the strain-induced conductivity decreases. The good reversible “on-off” behaviors for multiple cycles were also demonstrated. The results presented demonstrate a new strategy to control redox reactions simply by tensile strain, indicating the potential applications in future soft smart mechanotransduction devices.

Background: C-reactive protein (CRP) is a well-recognized biomarker of inflammation, which can be used as a predictor of cardiovascular disease. Evidence have suggested exposure to multiple metals/metalloids may affect immune system and give rise to cardiovascular disease. However, it is lack of study to comprehensively evaluate the association of multiple metals and CRP, the interactions between metals, and the gene-metal interaction in relation to CRP levels. Aims: To explore the associations of multiple plasma metals with serum CRP, and to test the interactions between metals, and gene-metal interactions on the levels of serum CRP. Methods: We included 2882 participants from the Dongfeng-Tongji cohort, China, and measured 23 plasma metals and serum CRP concentrations. The genetic risk score (GRS) was calculated based on 7 established CRP-associated variants. For metals which were associated with the levels of CRP, we further tested the interactions between metals on CRP, and analyzed the gene-metal interactions on CRP. Results: The median level for CRP in the total population was 1.17 mg/L. After multivariable adjustment, plasma copper was positively associated with serum CRP (FDR