Multifunctional Intelligent Reconfigurable Metasurface.

The emergent reconfigurable metasurfaces (RMs) have attracted a lot of attention due to their potential in broad applications. As a general platform, RMs are able to control the reflection (or refraction) of incident waves with predefined functionalities. Nevertheless, the operation of RMs is highly dependent on the arrival direction of incidence. The self-adaptive design of an RM, so that it can respond to varied incident waves automatically, is highly requested in practical implementation, which is actually challenging. This study reports the realization of an intelligent RM (IRM) system, which can detect the arrival direction of impinging waves and respond to the incidence with a predefined functionality accordingly. This IRM system is constructed by integrating a direction of the arrival estimation module, a frontend by the varactor-based metasurface, and a central control unit. In experiments, an IRM system designed for TM polarization is demonstrated to perform various functions, i.e., retroreflection, directional reflection, and fixed-point energy focusing, which are highly requested by edge communication and sensing. The measured results imply that this IRM system responds quite well within a wide incident range from -60° to 60° in a frequency range from 9 to 9.5 GHz. The proposed IRM can be a good candidate for boosting 5G communication and Internet of Things applications, including beam shaping/steering, RCS manipulation, object imaging, and sensor recharging.

Tumor-associated macrophages/C-X-C motif chemokine ligand 1 promotes breast cancer autophagy-mediated chemoresistance via IGF1R/STAT3/HMGB1 signaling.

Autophagy-mediated chemoresistance is the core mechanism for therapeutic failure and poor prognosis in breast cancer. Breast cancer chemotherapy resistance is believed to be influenced by tumor-associated macrophages (TAMs), by which C-X-C motif chemokine ligand 1 (CXCL1) is the most abundant cytokine secreted. Yet, its role in mediating autophagy-related chemoresistance is still unknown. This study aimed to explore the molecular mechanisms by which TAMs/CXCL1 induced autophagy-mediated chemoresistance in breast cancer. It was found that TAMs/CXCL1 promoted chemoresistance of breast cancer cells through autophagy activation in vitro, and CXCL1 silence could enhance the chemosensitivity of paclitaxel-resistant breast cancer cells via autophagy inhibition. A high-throughput quantitative PCR chip and subsequent target validation showed that CXCL1 induced autophagy-mediated chemoresistance by inhibiting VHL-mediated IGF1R ubiquitination. The elevated IGF1R then promoted STAT3/HMGB1 signaling to facilitate autophagy. Additionally, TAMs/CXCL1 silence improved paclitaxel chemosensitivity by suppressing autophagy in breast cancer mice xenografts, and clinical studies further linked CXCL1 to IGF1R/HMGB1 signaling, as well as shorter free survival of recurrence. Taken together, these results not only uncover the crucial role of TAMs/CXCL1 signaling in mediating breast cancer chemoresistance through enhancing autophagy, but also shed novel light on the molecular mechanism of IGF1R/STAT3/HMGB1 pathway in regulating autophagy and its impact on cancer prognosis.

Association between air pollution and bone mineral density: a Mendelian randomization study.

Introduction: The association of air pollution with bone mineral density (BMD) has attracted increasing attention. However, establishing a causal relationship remains uncertain. Methods: We conducted a Mendelian randomization (MR) study employing PM2.5, PM2.5-10, PM10, nitrogen dioxide, and nitrogen oxides as exposures and BMD as the outcome to explore the causality between air pollution and the occurrence of decreased BMD. Results: By employing the IVW method, we identified a negative causality between air pollution (PM2.5, PM10, and nitrogen oxides) and BMD. Conclusions: Our findings demonstrate that PM2.5, PM10 and nitrogen oxides exposure may contribute to decreased BMD.

Physical-Matched Nanoplatelets Boost Heterogeneous Thrombi Targeting Through Self-Adaptive Deformation for Thrombolysis and Endothelial Repairing.

The heterogeneity of thrombi in terms of composition, structure, and blood rheology parameters presents a challenge for effective thrombus-targeting drug delivery. To address this, a self-adaptive nano-delivery system, termed D-PLT, is developed. It consists of platelet membrane-cloaked deformable mesoporous organic silicon dioxide nanocomposite, enabling it to respond to the challenge of the heterogeneity of thrombi in arteries and veins. The system exhibits progressive targeting, with the ability to target arterial and venous thrombosis and damaged blood vessels. D-PLT physically matches the pore structure of the thrombus by undergoing varied deformation, leading to advanced targeting and enrichment of arterial and venous thrombus. When co-loaded with the thrombolytic drug urokinase (UK) and the endothelium-protecting agent atorvastatin calcium (AT), the system improves rapid vascular opening of arterial and venous thrombosis in 90 min and provides up to 7 days of durable thrombolysis and recovery from endothelial dysfunction in vivo. This self-adaptive delivery system offers a promising strategy to overcome thrombus heterogeneity.

No genetic causal relationship between lung function and osteoporosis - evidence from a mendelian randomization study.

For a long time, the decline in lung function has been regarded as a potential factor associated with the risk of osteoporosis (OP). Although several observational studies have investigated the relationship between lung function and OP, their conclusions have been inconsistent. Given that Mendelian randomization (MR) studies can help reduce the interference of confounding factors on outcomes, we adopted this approach to explore the causal relationship between lung function and OP at the genetic level. To investigate the potential causality between lung function (FVC, FEV1, FEV1/FVC, PEF) and OP, we conducted a MR analysis employing three approaches: inverse variance weighted (IVW), MR-Egger, and weighted median. We used Cochran's Q test to detect potential heterogeneity, MR-Egger regression to evaluate directional pleiotropy, and the MR-PRESSO method to evaluate horizontal pleiotropy. In addition, we used MR-PRESSO and MR radial methods to exclude SNPs exhibiting pleiotropic outliers. Upon identification of potential outliers, we removed them and subsequently ran MR analysis again to assess the reliability of our findings. The MR analysis suggested that there was no causal effect of lung function (FVC, PEF, FEV1/FVC, FEV1) on OP, which is consistent with the. results after excluding potential outliers using MR-PRESSO and MR radial. methods. Sensitivity analysis confirmed the reliability and consistency of these. results. The study concluded that there is no causal link between lung function and OP. The association found in observational studies might be attributable to shared risk factors.

Lanthanide-Doped Nanoparticles Anchoring on Metal-Organic Frameworks with Thermally Enhanced Upconversion Luminescence for Sensitive Nanothermometers.

Nanothermometers can detect changes in the local temperature in living cells and in vivo, revealing fundamental biological properties. Despite the exploration of different temperature-responsive materials, the design and development of temperature-sensing probes with high brightness and high sensitivity remain a daunting challenge. Here, we employed the UiO-66 type metal-organic frameworks (MOFs) to anchor UNCPs on the surface of the MOFs for constructing MOF@UCNPs nanohybrids. The in situ composite method with MOFs leads to the coordination interaction between the ligands and the surface of UCNPs, enabling controlled composite formation between different MOFs and UCNPs. Remarkably, the surface interaction favors the anomalous thermo-enhanced luminescence, achieving a 35-fold enhancement of UiO-66@NaYF4:Yb/Tm at 413 K. Furthermore, these MOF@UCNPs nanohybrids with thermo-enhanced luminescence are developed as multifunctional biological probes for bioimaging and intracellular temperature sensing, demonstrating a high thermal sensitivity of 1.92% K-1 in the physiological temperature range. Based on these findings, temperature monitoring of the local position was successfully carried out by the designed MOF@UCNPs nanoprobes in vivo. These findings underscore the potential of MOF@UCNPs nanohybrids, opening up new avenues for the development of a multifunctional platform for biological analysis.

Gradient Thermal Annealing Assisted Perovskite Film Crystallization Regulation for Efficient and Stable Photovoltaic-Photodetection Bifunctional Device.

Perovskite crystallization regulation is essential to obtain excellent film optoelectronic properties and device performances. However, rapid crystallization during annealing always results in poor perovskite film and easy formation of trap, thereby greatly restricting device performance due to severe non-radiative recombination. Here, an easy and reproducible gradient thermal annealing (GTA) approach is used to regulate the perovskite crystallization. Through a low-temperature initial annealing of GTA, the solvent evaporation is slowed down, thus extending nucleation time and providing a buffer for the rapid crystallization of perovskite grains in the subsequent high-temperature stage. As a result, completely converted and highly crystalline perovskite is obtained with 1.6 times larger grain size, reduced trap density and suppressed non-radiative recombination of photo-generated carriers. The film crystallinity is also enhanced with more advantageous (100) and (111) lattice facets which are favorable for carrier transport. Consequently, the perovskite photodetectors exhibit a large linear dynamic range of 174 dB and an excellent response even under ultra-weak light of 303 pW. Meanwhile, perovskite solar cells achieved increased PCE and maintained 85% of original efficiency after heating at 65 °C for nearly 1000 h under unencapsulated conditions. To the knowledge, this represents the best performance reported for a perovskite photovoltaic-photodetection bifunctional device.

Associations between dietary nutrient intake and sleep disorders in cancer survivors base on NHANES 2005 to 2018.

Sleep disorders significantly impact the quality of life for many individuals, which remain largely unrecognized. It is widely believed that dietary nutrient intake plays a crucial role in promoting healthy sleep patterns. However, there is lack of research focusing on cancer survivors. This study utilized the National Health and Nutrition Examination Survey (NHANES) database to investigate the correlation between dietary nutrient intake and sleep disorders in cancer survivors. Analyzing data from 2882 cancer survivors in NHANES spanning from 2005 to 2018. Dietary nutrient intake was evaluated through two 24-h dietary recalls. Weighted multivariable logistic regression model was employed to further applied to explore the association between dietary fiber intake and sleep disorders while controlling for relevant confounding factors. Additionally, the nonlinear and dose-response relationships were explored using restricted cubic spline (RCS) regression along with smooth curve fitting and threshold effect analysis. Stratified analysis and interaction analysis were conducted to assess the consistency of the results. Univariable and multivariable analysis demonstrated that dietary fiber intake showed negative correlation with sleep disorders (P < 0.05). Treating dietary fiber intake as continuous variable. After accounting for all covariates, the study reaffirmed the protective role of dietary fiber (odds ratio [OR]: 0.99, 95% confidence interval [CI]: 0.98-0.99, P = 0.044). Analysis of dietary fiber intake in quartiles further supported this trend (P < 0.001). Interestingly, further investigations indicated that dietary fiber intake was not associated with sleep apnea, insomnia, restless legs syndrome, or other types of sleep disorders (P > 0.05). Notably, no statistically significant interactions were observed in all subgroup analyses except poverty income ratio (PIR) (P for interaction < 0.05), indicating that the protective effect of dietary fiber on sleep disorders was more pronounced in individuals with PIR ≥ 2.5. Our results suggest that adequate dietary fiber intake may be beneficial dietary strategy to reduce sleep disorders in cancer survivors.

Non-discriminating engineered masking of immuno-evasive ligands on tumour-derived extracellular vesicles enhances tumour vaccination outcomes.

The success of personalized cancer immunotherapy depends on the initial tumour antigenic presentation to dendritic cells and macrophages. Tumour-derived extracellular vesicles (TEVs) contain abundant tumour antigenic molecules. The presence of anti-phagocytotic signals such as cluster of differentiation 47 (CD47) on the surface of the TEVs, however, leads to evasion of the same dendritic cells and macrophages. Here we show that iron oxide hydroxide nanocomposites can successfully mask TEV surfaces and unblock phagocytosis without affecting extracellular vesicles' elicited immune goals. After internalization, the mask disintegrates in the lysosome, releasing the tumour antigenic cargo. This triggers antigen presentation and promotes dendritic cell activation and maturation and macrophage reprogramming in animal models, leading to a drastic reduction of tumour volume and metastasis, and in human malignant pleural effusion clinical samples. This straightforward masking strategy eliminates the ubiquitous anti-phagocytosis block found in clinical samples and can be applied universally across all patient-specific TEVs as tumour antigenic agents for enhanced immunotherapy.

Ganoderma lucidum spore powder after oil extraction alleviates microbiota dysbiosis to improve the intestinal barrier function in mice.

BACKGROUND: There are few studies about the differences in the composition of moisture, ash, crude protein, crude fat, crude polysaccharide and ergothioneine in Ganoderma lucidum spore powder (GLSP) from different origins. As for GLSP after oil extraction (OE-GLSP), there are still lots of bioactive substance in it. It can be seen that OE-GLSP has certain biological activity. The effect of OE-GLSP on the improvement of intestinal barrier function has been less studied. RESULTS: The results showed that there were significant differences for GLSP from five different origins (Anhui, Jilin, Jiangxi, Shandong and Zhejiang) in moisture (0.065-0.113%), ash (0.603-0.955%), crude fat (42.444-44.773%), crude polysaccharide (2.977-4.127%), crude protein (14.761-17.639%) and ergothioneine (0.552-1.816 mg g-1) (P < 0.05). The monosaccharides of GLSP polysaccharide mainly consist of glucose, galactose, mannose, rhamnose, etc. Moreover, the effects of OE-GLSP supplementation on the regulation of organ index, colonic tissue and intestinal microbiota in C57BL/6J mice were investigated. The supplement of OE-GLSP could restore the organ index and weight loss of antibiotic-treated mice. Moreover, OE-GLSP led to the improvement of intestinal dysbiosis by enriching Bacteroidetes, Firmicutes, Lactobacillus and Roseburia, and increasing the Firmicutes/Bacteroidetes ratio. In addition, OE-GLSP intervention repaired intestinal barrier dysfunction by increasing the expression of tight junction proteins (Occludin, Claudin-1 and E-cadherin). CONCLUSION: Different GLSP from five origins exhibited significant differences in microstructure and contents of crude polysaccharide, crude protein, crude fat, water, ash and ergothioneine. Moreover, it was found that OE-GLSP could improve the intestinal barrier function and induce potentially beneficial changes in intestinal flora. © 2024 Society of Chemical Industry.

XIAOPI formula inhibits chemoresistance and metastasis of triple-negative breast cancer by suppressing extracellular vesicle/CXCL1-induced TAM/PD-L1 signaling.

BACKGROUND: Triple-negative breast cancer (TNBC) is challenged by the low chemotherapy response and poor prognosis. Emerging evidence suggests that cytotoxic chemotherapy may lead to the pro-metastatic tumor microenvironment (TME) by eliciting pro-tumor extracellular vesicles (EVs) from cancer cells. However, the precise mechanisms and therapeutic approaches remain inadequately understood. PURPOSE: This study aims to determine whether XIAOPI formula (Chinese name XIAOPI San, XPS), a nationally sanctioned medication for mammary hyperplasia, can chemosensitize TNBC by remodeling the TME via modulating EV signaling, and exploring its underlying mechanisms. METHODS: Multiple methodologies, such as EV isolation, transmission electron microscope, flow cytometry, dual-luciferase reporter assays, co-immunoprecipitation and in vivo breast cancer xenograft, were employed to elucidate the effect and molecular mechanisms of XPS on paclitaxel-induced EV signaling (EV-dead) of TNBC. RESULTS: XPS, at non-toxic concentrations, synergized with PTX to inhibit the invasion and chemoresistance of TNBC cells co-cultured with macrophages. Compared to EV-dead, XPS co-treatment-elicited EVs (EV-deadXPS) exhibited a decreased capacity to promote the invasion, chemoresistance and cancer stem cell subpopulation of the co-cultured TNBC cells. Mechanistically, XPS administration led to a reduction in CXCL1 cargo in EV-dead, and thereby attenuated its activation effect on macrophage polarization into M2 phenotype through the transcriptional downregulation of PD-L1 expression. Furthermore, XPS effectively reduced the number of EV-dead from TNBC cells by inhibiting CXCL1-mediated intraluminal vesicle (ILV) biogenesis in multivesicular bodies (MVBs). Moreover, molecular explorations revealed that XPS impaired ILV biogenesis by disrupting the RAB31/FLOT2 complex via suppressing the CXCL1/Myc signaling. Importantly, XPS significantly chemosensitized paclitaxel to inhibit TNBC growth and metastasis in vivo by suppressing EV-deadCXCL1-induced PD-L1 activation and M2 polarization of macrophages. CONCLUSION: This pioneering study not only sheds novel light on EV-deadCXCL1 as a potential therapeutic target to suppress TNBC chemoresistance and metastasis, but also provides XPS as a promising adjuvant formula to chemosensitize TNBC by remodeling EV-deadCXCL1-mediated immunosuppressive TME.

Living-Skin Detection based on Spatio-Temporal Analysis of Structured Light Pattern.

Living-skin detection is an important step for imaging photoplethysmography and biometric anti-spoofing. In this paper, we propose a new approach that exploits spatio-temporal characteristics of structured light patterns projected on the skin surface for living-skin detection. We observed that due to the interactions between laser photons and tissues inside a multi-layer skin structure, the frequency-domain sharpness feature of laser spots on skin and non-skin surfaces exhibits clear difference. Additionally, the subtle physiological motion of living-skin causes laser interference, leading to brightness fluctuations of laser spots projected on the skin surface. Based on these two observations, we designed a new living-skin detection algorithm to distinguish skin from non-skin using spatio-temporal features of structured laser spots. Experiments in the dark chamber and Neonatal Intensive Care Unit (NICU) demonstrated that the proposed setup and method performed well, achieving a precision of 85.32%, recall of 83.87%, and F1-score of 83.03% averaged over these two scenes. Compared to the approach that only leverages the property of multilayer skin structure, the hybrid approach obtains an averaged improvement of 8.18% in precision, 3.93% in recall, and 8.64% in F1-score. These results validate the efficacy of using frequency domain sharpness and brightness fluctuations to augment the features of living-skin tissues irradiated by structured light, providing a solid basis for structured light based physiological imaging. Our code is available at: https://github.com/contactless-healthcare/Structured-light-based-Living-skin-Detection.

Application of acid-activated near-infrared viscosity fluorescent probe targeting lysosomes in cancer visualization.

The higher viscosity and lower pH in lysosomes of cancer cells highlight their potential as biomarkers for cancer. Therefore, the development of acid-activated viscosity fluorescent probes is significant for the early diagnosis and treatment of cancer. Based on this, we have designed and synthesized a near-infrared fluorescent probe based on the 2-(2-hydroxyphenyl)benzothiazole (HBT) group, namely HBTH, to monitor the viscosity changes within lysosomes. It has been demonstrated that HBTH was extremely sensitive to viscosity, with a strong linear relationship between fluorescence intensity and log(viscosity) within the range of (logη) = 0-3.06 (a correlation coefficient of 0.98), proving its capability for quantitative viscosity measurement. In particular, the most obvious fluorescence enhancement of HBTH was only efficiently triggered by the combined effect of low pH and high viscosity. Furthermore, HBTH can rapidly localize to lysosomes by wash-free procedure at a low concentration (100 nM) and achieve high-fidelity imaging within 20 s. It can also monitor the dynamic processes of lysosomes in cells, viscosity changes under drug stimuli, and lysosomal behavior during mitophagy. Importantly, HBTH is capable of identifying tumors in tumor-bearing nude mice through in vivo imaging. These features make HBTH a powerful tool for the early diagnosis and treatment of cancer.

Single-cell sequencing and multiple machine learning algorithms to identify key T-cell differentiation gene for progression of NAFLD cirrhosis to hepatocellular carcinoma.

Introduction: Hepatocellular carcinoma (HCC), which is closely associated with chronicinflammation, is the most common liver cancer and primarily involves dysregulated immune responses in the precancerous microenvironment. Currently, most studies have been limited to HCC incidence. However, the immunopathogenic mechanisms underlying precancerous lesions remain unknown. Methods: We obtained single-cell sequencing data (GSE136103) from two nonalcoholic fatty liver disease (NAFLD) cirrhosis samples and five healthy samples. Using pseudo-time analysis, we systematically identified five different T-cell differentiation states. Ten machine-learning algorithms were used in 81 combinations to integrate the frameworks and establish the best T-cell differentiation-related prognostic signature in a multi-cohort bulk transcriptome analysis. Results: LDHA was considered a core gene, and the results were validated using multiple external datasets. In addition, we validated LDHA expression using immunohistochemistry and flow cytometry. Conclusion: LDHA is a crucial marker gene in T cells for the progression of NAFLD cirrhosis to HCC.

Brozopine ameliorates cognitive impairment via upregulating Nrf2, antioxidation and anti-inflammation activities.

Oxidative stress and inflammation are crucial factors contributing to the occurrence and development of vascular dementia (VD). In a previous study, we demonstrated that brozopine (BZP) is an anti-ischemic drug. In this study, a model of VD in rats with modified permanent bilateral common carotid artery occlusion (2-VO) was established in vivo, a model of cellular excitotoxicity/oxidative stress was established via L-glutamate-induced PC12 cell injury, a model of neuroinflammation was established in LPS-induced BV2 cells in vitro, and the ameliorative effect of BZP on cognitive impairment was assessed. BZP treatment improved memory deficit in VD rats through inhibiting Ca2+overload and the levels of oxidative stress, ferroptosis, and inflammatory markers (IL-1ß, IL-6, and COX-2) in different brain regions. Additionally, we found that the levels of inflammatory markers in the plasma were also reduced in the VD rats. BZP was further found to have antioxidative stress, antiferroptosis (ferroptosis markers: GPX4, P53, and ACSL4), and antineuroinflammatory effects in PC12 and BV2 cells. Its mechanisms of action were found to be related to the activation of the Nrf2/TLR4/NF-κB pathway; the protective effect of BZP was partially inhibited after using Nrf2-specific inhibitors. Thus, BZP has therapeutic properties for the potential mitigation of cognitive impairment.

Acidity-activatable dynamic hybrid nanoplatforms derived from extracellular vesicles of M1 macrophages enhance cancer immunotherapy through synergistic triple immunotherapy.

Immunotherapy exhibits considerable promise for sustained tumor reduction. However, current cancer immunotherapy methods elicit limited responses due to the inadequate immunogenicity exhibited by cancer cells. This obstacle may be addressed using nanoplatforms that can activate synergistic therapies (photodynamic therapy and ferroptosis) in response to the acidic pH of the tumor microenvironment. We previously developed an amphiphilic photosensitizer, SR780, which displays satisfactory photodynamic effects. This photosensitizer is inactivated when bound to Fe3+ (SR780Fe) but is activated upon release in mildly acidic conditions. In this study, M1 macrophage-derived extracellular vesicles (EVs) were fused with REV and SR780Fe-loaded liposomes (REV@SR780Fe@Lip) to form REV@SR780Fe@LEV hybrid nanovesicles. Further modification with the RS17 peptide for tumor targeting enabled a combination of photodynamic therapy, ferroptosis, and cGAS-STING pathway activation, resulting in enhanced antitumor efficacy through a synergistic effect. Upon laser irradiation, REV@SR780Fe@LEV-RS17 demonstrated antitumor effects in 4T1 breast cancer models, including the inhibition of lung and liver metastasis, as well as prevention of tumor recurrence.

Baohuoside I chemosensitises breast cancer to paclitaxel by suppressing extracellular vesicle/CXCL1 signal released from apoptotic cells.

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype and chemotherapy is the cornerstone treatment for TNBC. Regrettably, emerging findings suggest that chemotherapy facilitates pro-metastatic changes in the tumour microenvironment. Extracellular vesicles (EVs) have been highly implicated in cancer drug resistance and metastasis. However, the effects of the EVs released from dying cancer cells on TNBC prognosis and corresponding therapeutic strategies have been poorly investigated. This study demonstrated that paclitaxel chemotherapy elicited CXCL1-enriched EVs from apoptotic TNBC cells (EV-Apo). EV-Apo promoted the chemoresistance and invasion of co-cultured TNBC cells by polarizing M2 macrophages through activating PD-L1 signalling. However, baohuoside I (BHS) remarkably sensitized the co-cultured TNBC cells to paclitaxel chemotherapy via modulating EV-Apo signalling. Mechanistically, BHS remarkably decreased C-X-C motif chemokine ligand 1 (CXCL1) cargo within EV-Apo and therefore attenuated macrophage M2 polarization by suppressing PD-L1 activation. Additionally, BHS decreased EV-Apo release by diminishing the biogenesis of intraluminal vesicles (ILVs) within multivesicular bodies (MVBs) of TNBC cells. Furthermore, BHS bound to the LEU104 residue of flotillin 2 (FLOT2) and interrupted its interaction with RAS oncogene family member 31 (RAB31), leading to the blockage of RAB31-FLOT2 complex-driven ILV biogenesis. Importantly, BHS remarkably chemosensitised paclitaxel to inhibit TNBC metastasis in vivo by suppressing EV-ApoCXCL1-induced PD-L1 activation and M2 polarization of tumour-associated macrophages (TAMs). This pioneering study sheds light on EV-ApoCXCL1 as a novel therapeutic target to chemosensitise TNBC, and presents BHS as a promising chemotherapy adjuvant to improve TNBC chemosensitivity and prognosis by disturbing EV-ApoCXCL1 biogenesis.

Tanshinone I improves TNBC chemosensitivity by suppressing late-phase autophagy through AKT/p38 MAPK signaling pathway.

The inhibition of autophagy is a potential therapeutic strategy to improve the chemosensitivity of triple-negative breast cancer (TNBC). In this study, we demonstrated that a natural terpenoid tanshinone I (TAN) enhanced the effectiveness of paclitaxel (PTX), at least in part, through an autophagy-dependent mechanism against TNBC. In vitro validation demonstrated that the combined therapy resulted in a synergistic decrease in the growth of TNBC cells. The chemosensitizing impact of TAN might be attributed to its inhibition of PTX-induced autophagy in the late phase by obstructing the fusion of autophagosomes and lysosomes, rather than by inhibiting lysosomal function. The findings from KEGG pathway analysis and molecular docking suggested that TAN might impact breast cancer chemoresistance primarily through the PI3K-Akt and MAPK signaling pathways. The non-canonical AKT/p38 MAPK signaling was further validated as the primary mechanism responsible for the inhibition of autophagy by TAN. In vivo study showed that the combined administration of TAN and PTX demonstrated a more significant suppression of tumor growth and autophagic activity compared to PTX monotherapy in the MDA-MB-231 xenograft nude mouse model. The safety evaluation of TAN in a zebrafish model, along with in vitro and in vivo validation, provided experimental and pre-clinical data supporting its potential as a natural adjunctive therapy in TNBC. Overall, this study suggests that the combination of TAN with PTX could provide an effective treatment option for advanced breast cancer, and targeting the AKT/p38 MAPK/late-autophagy signaling axis may be a promising approach for developing therapeutic interventions against TNBC.

Molecular Dynamics Simulation of the Rejuvenation Performance of Waste Cooking Oil with High Acid Value on Aged Asphalt.

Waste cooking oil's (WCO's) potential as a rejuvenator of aged asphalt has received attention in recent years, with the acid value of WCO affecting its rejuvenation effect. This study explored the rejuvenation effect of WCO with a high acid value on aged asphalt by using molecular dynamics simulation. First, the representative molecules of WCO with a high acid value and asphalt were determined. The rejuvenation effect of WCO on aged asphalt was analyzed by adding different contents of WCO to an aged asphalt model. The effect of WCO on the thermodynamic properties of the aged asphalt was analyzed. The results show that WCO can restore the thermodynamic properties of aged asphalt binder to a certain extent. Regarding the microstructure of rejuvenated asphalt, WCO molecules dispersed around asphaltenes weakened the latter's aggregation and improved the colloidal structure of the aged asphalt. In terms of interface adhesion properties, WCO can improve the adhesion properties between asphalt binder and SiO2, but it has limited influence on water sensitivity. The results allowed us to comprehensively evaluate the rejuvenation effect of WCO with a high acid value on aged asphalt and to explore its rejuvenation mechanism.

Methyl methacrylate-modified polystyrene microspheres: an effective strategy to enhance the fluorescence of Eu-complexes.

The in vitro detection applications of europium complex-doped microspheres mainly rely on strong fluorescence intensity and a well-defined morphology. In this work, using methyl methacrylate-modified polystyrene microspheres has been proven an effective strategy to enhance the fluorescence and morphology of Eu-complexes. The experimental results showed that the modification resulted in the formation of a porous structure within the polystyrene microspheres, enhancing the doping uniformity and facilitating a more significant accumulation of fluorescent molecules. Furthermore, because of their encapsulation ability, microspheres efficiently confine the fluorescent molecules within them. In addition, the nano-scale porous structure endowed the microspheres with enhanced properties without compromising solvent swelling capability, thereby significantly boosting the fluorescence performance of porous PSMMA. In lateral flow immunoassays (LFIAs), PSMMA-Eu microspheres were effectively utilized to detect fentanyl with exceptional sensitivity by capitalizing on these benefits, capable of detecting concentrations as low as 0.10 ng mL-1. This technology has significant potential for rapid point-of-care screening and clinical applications.