Biodegradable and Efficient Charge-Migrated Z-Scheme Heterojunction Amplifies Cancer Ferroptosis by Blocking Defensive Redox System.

Ferroptosis is an emerging non-apoptotic death process, mainly involving lipid peroxidation (LPO) caused by iron accumulation, which is potentially lethal to the intrinsically apoptotic-resistant malignant tumor. However, it is still restricted by the inherent antioxidant systems of tumor cells and the poor efficacy of traditional iron-based ferroptosis initiators. Herein, the study develops a novel ferroptosis-inducing agent based on PEGylated Cu+/Cu2+-doped black phosphorus@polypyrrole heterojunction (BP@CPP), which is constructed by utilizing the phosphate on the surface of BP to chelate Cu ions and initiating subsequent in situ polymerization of pyrrole. As a novel Z-scheme heterojunction, BP@CPP possesses an excellent photocatalytic activity in which the separated electron-hole pairs under laser irradiation endow it with powerful oxidizing and reducing capacities, which synergy with Cu+/Cu2+ self-cycling catalyzing Fenton-like reaction to further strengthen reactive oxygen species (ROS) accumulation, glutathione (GSH) depletion, and glutathione peroxidase 4 (GPX4) inactivation, ultimately leading to efficient ferroptosis. Systematic in vitro and in vivo evaluations demonstrate that BP@CPP effectively inhibit tumor growth by inducing desired ferroptosis while maintaining a favorable biosafety in the body. Therefore, the developed BP@CPP-based ferroptosis initiator provides a promising strategy for ferroptosis-like cancer therapy.

Bidirectional Enhancement of Nitrogen Removal by Indigenous Synergetic Microalgal-Bacterial Consortia in Harsh Low-C/N Wastewater.

Conventional microalgal-bacterial consortia have limited capacity to treat low-C/N wastewater due to carbon limitation and single nitrogen (N) removal mode. In this work, indigenous synergetic microalgal-bacterial consortia with high N removal performance and bidirectional interaction were successful in treating rare earth tailing wastewaters with low-C/N. Ammonia removal reached 0.89 mg N L-1 h-1, 1.84-fold more efficient than a common microalgal-bacterial system. Metagenomics-based metabolic reconstruction revealed bidirectional microalgal-bacterial interactions. The presence of microalgae increased the abundance of bacterial N-related genes by 1.5- to 57-fold. Similarly, the presence of bacteria increased the abundance of microalgal N assimilation by 2.5- to 15.8-fold. Furthermore, nine bacterial species were isolated, and the bidirectional promotion of N removal by the microalgal-bacterial system was verified. The mechanism of microalgal N assimilation enhanced by indole-3-acetic acid was revealed. In addition, the bidirectional mode of the system ensured the scavenging of toxic byproducts from nitrate metabolism to maintain the stability of the system. Collectively, the bidirectional enhancement system of synergetic microalgae-bacteria was established as an effective N removal strategy to broaden the stable application of this system for the effective treatment of low C/N ratio wastewater.

Resourceful application and mechanism of oyster shell-microalgae synergistic system：Sustainable treatment of harsh low carbon nitrogen ratio actual wastewater.

Microalgal technology holds great promise for both low C/N wastewater treatment and resource recovery simultaneously. Nevertheless, the advancement of microalgal technology is hindered by its reduced nitrogen removal efficiency in low C/N ratio wastewater. In this work, microalgae and waste oyster shells were combined to achieve a total inorganic nitrogen removal efficiency of 93.85% at a rate of 2.05 mg L-1 h-1 in low C/N wastewater. Notably, over four cycles of oyster shell reuse, the reactor achieved an average 85% ammonia nitrogen removal extent, with a wastewater treatment cost of only $0.092/ton. Moreover, microbial community analysis during the reuse of oyster shells revealed the critical importance of timely replacement in inhibiting the growth of non-functional bacteria (Poterioochromonas_malhamensi). The work demonstrated that the oyster shell - microalgae system provides a time- and cost-saving, environmental approach for the resourceful treatment of harsh low C/N wastewater.

Atomic Layers of B2 CuPd on Cu Nanocubes as Catalysts for Selective Hydrogenation.

The search for highly active and selective catalysts with high precious metal atom utilization efficiency has attracted increasing interest in both the fundamental synthesis of materials and important industrial reactions. Here, we report the synthesis of Pd-Cu nanocubes with a Cu core and an ordered B2 intermetallic CuPd shell with controllable atomic layers on the surface (denoted as Cu/B2 CuPd), which can efficiently and robustly catalyze the selective hydrogenation of acetylene (C2H2) to ethylene (C2H4) under mild conditions. The optimized Cu/B2 CuPd with a Pd loading of 9.5 at. % exhibited outstanding performance in the C2H2 semi-hydrogenation with 100% C2H2 conversion and 95.2% C2H4 selectivity at 90 °C. We attributed this outstanding performance to the core/shell structure with a high surface density of active Pd sites isolated by Cu in the B2 intermetallic matrix, representing a structural motif of single-atom alloys (SAAs) on the surface. The combined experimental and computational studies further revealed that the electronic states of Pd and Cu are modulated by SAAs from the synergistic effect between Pd and Cu, leading to enhanced performance compared with pristine Pd and Cu catalysts. This study provides a new synthetic methodology for making single-atom catalysts with high precious metal atom utilization efficiency, enabling simultaneous tuning of both geometric and electronic structures of Pd active sites for enhanced catalysis.

ScRNA-seq links dental fibroblasts heterogeneity with mechanoresponsiveness.

BACKGROUND AND OBJECTIVE: Periodontal ligament (PDL) and dental pulp (DP) share a common origin but have distinct biological and mechanical functions. To what extent the mechanoresponsive property of PDL can be attributed to its unique transcriptional profiles of cellular heterogeneity is unclear. This study aims to decipher cellular heterogeneity and distinct mechanoresponsive characteristics of odontogenic soft tissues and their underlying molecular mechanisms. MATERIALS AND METHODS: A single-cell comparison of digested human periodontal ligament (PDL) and dental pulp (DP) was performed using scRNA-seq. An in vitro loading model was constructed to measure mechanoresponsive ability. Dual-luciferase assay, overexpression, and shRNA knockdown were used to investigate the molecular mechanism. RESULTS: Our results demonstrate striking fibroblast heterogeneity across and within human PDL and DP. We demonstrated that a tissue-specific subset of fibroblasts existed in PDL exhibiting high expression of mechanoresponsive extracellular matrix (ECM) genes, which was verified by an in vitro loading model. ScRNA-seq analysis indicated a particularly enriched regulator in PDL-specific fibroblast subtype, Jun Dimerization Protein 2 (JDP2). Overexpression and knockdown of JDP2 extensively regulated the downstream mechanoresponsive ECM genes in human PDL cells. The force loading model demonstrated that JDP2 responded to tension and that knockdown of JDP2 effectively inhibited the mechanical force-induced ECM remodeling. CONCLUSIONS: Our study constructed the PDL and DP ScRNA-seq atlas to demonstrate PDL and DP fibroblast cellular heterogeneity and identify a PDL-specific mechanoresponsive fibroblast subtype and its underlying mechanism.

Recent Advances in NIR or X-ray Excited Persistent Luminescent Materials for Deep Bioimaging.

Due to their persistent luminescence, persistent luminescent (PersL) materials have attracted great interest. In the biomedical field, the use of persistent luminescent nanoparticles (PLNPs) eliminates the need for continuous in situ excitation, thereby avoiding interference from tissue autofluorescence and significantly improving the signal-to-noise ratio (SNR). Although persistent luminescence materials can emit light continuously, the luminescence intensity of small-sized nanoparticles in vivo decays quickly. Early persistent luminescent nanoparticles were mostly excited by ultraviolet (UV) or visible light and were administered for imaging purposes through ex vivo charging followed by injection into the body. Limited by the low in vivo penetration depth, UV light cannot secondary charge PLNPs that have decayed in vivo, and visible light does not penetrate deep enough to reach deep tissues, which greatly limits the imaging time of persistent luminescent materials. In order to address this issue, the development of PLNPs that can be activated by light sources with superior tissue penetration capabilities is essential. Near-infrared (NIR) light and X-rays are widely recognized as ideal excitation sources, making persistent luminescent materials stimulated by these two sources a prominent area of research in recent years. This review describes NIR and X-ray excitable persistent luminescence materials and their recent advances in bioimaging.

A pilot scale study on the treatment of rare earth tailings (REEs) wastewater with low C/N ratio using microalgae photobioreactor.

Microalgae appear to be a promising and ecologically safe way for nutrients removal from rare earth tailings (REEs) wastewater with CO2 fixation and added benefits of resource recovery and recycling. In this study, a pilot scale (50 L) co-flocculating microalgae photobioreactor (Ma-PBR) as constructed and operated for 140 days to treat REEs wastewater with low C/N ratio of 0.51-0.56. The removal rate of ammonia nitrogen (NH4+-N) reached 88.04% and the effluent residual concentration was as low as 9.91 mg/L that have met the Emission Standards of Pollutants from Rare Earths Industry (GB 26451-2011). Timely supplementation of trace elements was necessary to maintain the activity of microalgae and then prolonged the operation time. The dominant phyla in co-flocculating microalgae was Chlorophyta, the relative abundance of which was higher than 80%. Tetradesmus belonging to Chlorophyceae was the dominant genus with relative abundance of 80.35%. The results provided a practical support for the scaling-up of Ma-PBR to treat REEs wastewater.

Cu-Doped Polypyrrole with Multi-Catalytic Activities for Sono-Enhanced Nanocatalytic Tumor Therapy.

Nanocatalytic medicine is a burgeoning disease treatment model with high specificity and biosafety in which the nanocatalyst is the core of driving catalytic reaction to generate therapeutic outcomes. However, the robust defense systems in the pathological region would counteract nanocatalyst-initiated therapeutics. Here, a Cu-doped polypyrrole is innovatively developed by a facile oxidative polymerization reaction, which exhibits intriguing multi-catalytic activities, including catalyzing H2 O2 to generate O2 and · OH, and consuming reduced glutathione by a Cu(II)-Cu(I) transition approach. By decorating with sonosensitizers and DSPE-PEG, the obtained CuPPy-TP plus US irradiation can induce severe oxidative damage to tumor cells by amplifying oxidative stress and simultaneously relieving antioxidant capacity in tumors based on the highly effective sonochemical and redox reactions. The notable tumor-specific biodegradability, remarkable cell apoptosis in vitro, and tumor suppression in vivo are demonstrated in this work, which not only present a promising biocompatible antitumor nanocatalyst but also broaden the perspective in oxidative stress-based antitumor therapy.

The beneficial effects of genetically engineered Escherichia coli Nissle 1917 in obese C57BL/6J mice.

BACKGROUND: Genetically modified probiotics have potential for use as a novel approach to express bioactive molecules for the treatment of obesity. The objective of the present study was to investigate the beneficial effect of genetically modified Escherichia coli Nissle 1917 (EcN-GM) in obese C57BL/6J mice. METHODS: First, an obesity model in C57BL/6J mice was successfully established. Then, the obese mice were randomly assigned into three groups: obese mice (OB), obese mice + EcN-GM (OB + EcN-GM), and obese mice + orlistat (OB + orlistat) (n = 10 in each group). The three groups were gavaged with 0.3 ml of 1010 CFU/ml control EcN, EcN-GM (genetically engineered EcN) and 10 ml/kg orlistat. Body weight, food consumption, fat pad and organ weight, hepatic biochemistry and hepatic histopathological alterations were measured. The effects of EcN-GM on the levels of endocrine peptides and the intestinal microbiota were also analyzed. RESULTS: After supplementation for 8 weeks, EcN-GM was associated with decreases in body weight gain, food intake, fat pad and liver weight, and alleviation hepatocyte steatosis in obese mice. EcN-GM also increased the level of GLP-1 in serum and alleviated leptin and insulin resistance. Moreover, supplementation with EcN-GM increased the α-diversity of the intestinal microbiota but did not significantly influence the relative abundance of Firmicutes and Bacteroidetes. CONCLUSIONS: These results indicated that EcN-GM, a genetically modified E. coli strain, may be a potential therapeutic approach to treat obesity. The beneficial effect of EcN-GM may be independent of the alteration of the diversity and composition of the intestinal microbiota in obese mice.

Erianin-Loaded Photo-Responsive Dendrimer Mesoporous Silica Nanoparticles: Exploration of a Psoriasis Treatment Method.

Psoriasis is a chronic inflammatory skin disorder accompanied by excessive keratinocyte proliferation. Erianin (Eri) is an ideal drug candidate for inhibiting proliferation and inducing apoptosis in the treatment of psoriasis. However, Eri's poor water solubility and low penetration activity across the skin hinder its application in local medicine. In this study, we developed a novel photo-responsive dendritic mesoporous silica nanoparticle-based carrier to deliver erianin, improved its bioavailability, and achieved sustained-release effects. Spiropyran (SP), 3-aminopropyltriethoxysilane (APTES), and perfluorodecyltriethoxysilane (PFDTES) were conjugated to the outer surface, which allowed Eri to be released in response to UV radiation. The physicochemical properties of photo-responsive dendritic mesoporous silica nanoparticles (Eri-DMSN@FSP) were characterized via multiple techniques, such as using a Fourier-transform infrared spectrometer, a high-resolution transmission electron microscope, and nuclear magnetic resonance (NMR) spectroscopy. The anti-proliferative properties and light-triggered release of erianin-loaded photo-responsive dendritic mesoporous silica nanoparticles were assessed via the MTT assay and a drug release study in vitro. Erianin-loaded photo-responsive dendritic mesoporous silica nanoparticles (UV) exhibit a significantly enhanced HaCat cell-inhibiting efficacy compared to other formulations, as demonstrated by their extremely low cell viability of 10.0% (concentration: 500 mg/mL), indicating their capability to release a drug that responds to UV radiation. The cellular uptake of photo-responsive dendritic mesoporous silica nanoparticles (DMSN@FSP) was observed via confocal laser scanning microscopy (CLSM). These experimental results show that Eri-DMSN@FSP could be effectively endocytosed into cells and respond to ultraviolet light to release Eri, achieving a more effective psoriasis treatment. Therefore, this drug delivery system may be a promising strategy for addressing the question of Eri's delivery and psoriasis therapy.

Xanthatin Alleviates LPS-Induced Inflammatory Response in RAW264.7 Macrophages by Inhibiting NF-κB, MAPK and STATs Activation.

Xanthatin (XT) is a sesquiterpene lactone isolated from the Chinese herb Xanthium, which belongs to the Asteraceae family. In this study, we developed an inflammation model via stimulating macrophage cell line (RAW 264.7 cells) with lipopolysaccharide (LPS), which was applied to assess the anti-inflammatory effect and probable mechanisms of xanthatin. When compared with the only LPS-induced group, cells that were pretreated with xanthatin were found to decrease the amount of nitric oxide (NO), reactive oxygen species (ROS) and associated pro-inflammatory factors (TNF-α, IL-1ß and IL-6), and downregulate the mRNA expression of iNOS, COX-2, TNF-α, IL-1ß, and IL-6. Interestingly, phosphorylated levels of related proteins (STAT3, ERK1/2, SAPK/JNK, IκBα, p65) were notably increased only with the LPS-activated cells, while the expression of these could be reverted by pre-treatment with xanthatin in a dose-dependent way. Meanwhile, xanthatin was also found to block NF-κB p65 from translocating into the nucleus and activating inflammatory gene transcription. Collectively, these results demonstrated that xanthatin suppresses the inflammatory effects through downregulating the nuclear factor kappa-B (NF-κB), mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription (STATs) signaling pathways. Taken together, xanthatin possesses the potential to act as a good anti-inflammatory medication candidate.

Effect of blended learning with BOPPPS model on Chinese student outcomes and perceptions in an introduction course of health services management.

Although the teaching methods of the blended learning and BOPPPS (bridge-in, objective, preassessment, participatory learning, postassessment, and summary) model are proven to be successful and highly effective at improving the academic knowledge of the students, respectively, it is unclear whether blended learning combined with the BOPPPS model (BL-BOPPPS) could work well in an introduction course of health services management (HSM) for the health management students in China. The study investigated the perceptions and effects of implementing the BL-BOPPPS model on student learning outcomes in an introduction course of HSM. The intervention group consisted of 55 students introduced to the BL-BOPPPS model, while the control group consisted of 54 students who received a conventional lecture. After the end of course, the effectiveness of teaching was self-assessed with questionnaires by all students, and examination scores for the two groups were compared. The students' satisfaction levels of BL-BOPPPS teaching strategy were up to 81.8% in the intervention group. Compared with the control group, the intervention group showed significant elevation of perception scores of skills (P = 0.001), initiative (P = 0.002), self-control (P = 0.008), self-efficacy (P = 0.001), motivation (P = 0.004), and the academic performance (P = 0.001). The BL-BOPPPS model could stimulate the enthusiasm and interest of health students; boost students' skills, initiative, and motivation in learning; and improve the self-directed learning ability, academic performance, and teaching quality. The findings provide a basis of evidence for the promotion of the BL-BOPPPS model in various disciplines in Chinese colleges and universities.

Dual role of RACK1 in airway epithelial mesenchymal transition and apoptosis.

Airway epithelial apoptosis and epithelial mesenchymal transition (EMT) are two crucial components of asthma pathogenesis, concomitantly mediated by TGF-ß1. RACK1 is the downstream target gene of TGF-ß1 shown to enhancement in asthma mice in our previous study. Balb/c mice were sensitized twice and challenged with OVA every day for 7 days. Transformed human bronchial epithelial cells, BEAS-2B cells were cultured and exposed to recombinant soluble human TGF-ß1 to induced apoptosis (30 ng/mL, 72 hours) and EMT (10 ng/mL, 48 hours) in vitro, respectively. siRNA and pharmacological inhibitors were used to evaluate the regulation of RACK1 protein in apoptosis and EMT. Western blotting analysis and immunostaining were used to detect the protein expressions in vivo and in vitro. Our data showed that RACK1 protein levels were significantly increased in OVA-challenged mice, as well as TGF-ß1-induced apoptosis and EMT of BEAS-2B cells. Knockdown of RACK1 (siRACK1) significantly inhibited apoptosis and decreased TGF-ß1 up-regulated EMT related protein levels (N-cadherin and Snail) in vitro via suppression of JNK and Smad3 activation. Moreover, siSmad3 or siJNK impaired TGF-ß1-induced N-cadherin and Snail up-regulation in vitro. Importantly, JNK gene silencing (siERK) also impaired the regulatory effect of TGF-ß1 on Smad3 activation. Our present data demonstrate that RACK1 is a concomitant regulator of TGF-ß1 induces airway apoptosis and EMT via JNK/Smad/Snail signalling axis. Our findings may provide a new insight into understanding the regulation mechanism of RACK1 in asthma pathogenesis.

MicroRNA-331-3p inhibits epithelial-mesenchymal transition by targeting ErbB2 and VAV2 through the Rac1/PAK1/ß-catenin axis in non-small-cell lung cancer.

MicroRNAs have been reported to play critical roles in the regulation of non-small-cell cancer (NSCLC) development, but the role of microRNA (miR)-331-3p in NSCLC is still unclear. In this study, the expression levels of miR-331-3p in NSCLC tumor tissues and adjacent normal tissues were examined by quantitative RT-PCR, and the relationship between miR-331-3p expression and patient clinicopathological characteristics was analyzed. The effects of miR-331-3p on epithelial-mesenchymal transition (EMT), migration, and metastasis of NSCLC cells were determined in vitro and vivo. Direct functional targets of miR-331-3p were identified by luciferase reporter assay, western blot assay, immunohistochemical staining, and rescue assay. The downstream pathway regulated by miR-331-3p was identified by immunofluorescence, immunoprecipitation, and Rac1 activity examination. Our results showed that miR-331-3p was significantly downregulated in NSCLC tumor tissues and was correlated with clinicopathological characteristics, and miR-331-3p could be an independent prognostic marker for NSCLC patients. Furthermore, miR-331-3p significantly suppressed EMT, migration and metastasis of NSCLC cells in vitro and in vivo. Both ErbB2 and VAV2 were direct functional targets of miR-331-3p. The activities of Rac1, PAK1, and ß-catenin were regulated by miR-331-3p through ErbB2 and VAV2 targeting. These results indicated that miR-331-3p suppresses EMT, migratory capacity, and metastatic ability by targeting ErbB2 and VAV2 through the Rac1/PAK1/ß-catenin axis in NSCLC.

Cimifugin Inhibits Inflammatory Responses of RAW264.7 Cells Induced by Lipopolysaccharide.

BACKGROUND RAW264.7 cells are induced by lipopolysaccharide (LPS) as a rheumatoid arthritis (RA) model. The present study investigated the effect of cimifugin on the proliferation, migration, chemotaxis, and release of inflammation-related factors and inflammation-related signaling pathways of LPS-induced RAW264.7 cells. MATERIAL AND METHODS MTS assay was used to determine the proliferation of RAW264.7 cells. Transwell assay was employed to examine the migration and chemotaxis of the cells. ELISA was performed to measure the contents of chemotactic factors and inflammatory factors in cell culture supernatants. Western blotting was carried out to detect the expression of factors related with MAPKs and NF-κB signaling pathways. RESULTS Cimifugin (0-100 mg/L) had no cytotoxicity for RAW264.7 cells. LPS stimulation induced morphological differentiation of RAW264.7 cells, but intervention by cimifugin inhibited the activation effect by LPS by about 50%. Cimifugin (100 mg/L) decreased the migration and chemotaxis of RAW264.7 cells to 1/3 of that in control cells by decreasing the release of migration- and chemotaxis-associated factors by at least 30%. Cimifugin (100 mg/L) suppressed the release of inflammatory factors from RAW264.7 cells to less than 60% of that in the LPS group. In addition, cimifugin (100 mg/L) inhibited the activities of MAPKs and NF-κB signaling pathways. CONCLUSIONS The present study demonstrates that cimifugin reduces the migration and chemotaxis of RAW264.7 cells and inhibits the release of inflammatory factors and activation of related signaling pathways induced by LPS. Cimifugin may have potential pharmacological effects against RA.

Identification and Interaction Analysis of Molecular Markers in Colorectal Cancer by Integrated Bioinformatics Analysis.

BACKGROUND Colorectal cancer (CRC) is an extremely common gastrointestinal malignancy. MATERIAL AND METHODS Three mRNA and 2 microRNA microarray datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) and microRNAs (DEMs) were obtained. The Database for Annotation, Visualization, and Integrated Discovery (DAVID) program was utilized to perform gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Protein-protein interaction (PPI) network analysis was performed with the Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape and Molecular Complex Detection (MCODE). Kaplan-Meier curves were plotted to determine overall survival (OS) estimates. DEMs targets were predicted by miRWalk. Quantitative reverse transcription polymerase chain reaction (QRT-PCR) was utilized to detect the expression of genes and microRNAs. RESULTS A total of 264 DEGs and 8 DEMs were obtained. GO analysis revealed that the DEGs were enriched in terms of cell structure, digestion, receptor binding, and extracellular material (ECM). KEGG pathway analysis showed that the DEGs were enriched in ECM interaction and mineral absorption. Additionally, a PPI network consisting of 181 nodes and 450 edges was established. Three modules with 38 high-degree hubs were extracted from the PPI network and found to be involved in pathways such as chemokine signaling. Five DEGs located in the network of DEM-DEG pairs were associated with the overall survival of CRC patients. Furthermore, hsa-miR-551b was demonstrated to be significantly down-regulated in CRC tissues. CONCLUSIONS The key biomarkers could provide new clues for CRC.

Electrifying Energy and Chemical Transformations with Single-Atom Alloy Nanoparticle Catalysts.

Single-atom alloys (SAAs) have attracted considerable attention as promising electrocatalysts in reactions central to energy conversion and chemical transformation. In contrast to monometallic nanocrystals and metal alloys, SAAs possess unique and intriguing physicochemical properties, positioning them as ideal model systems for studying structure-property relationships. However, the field is still in its early stages. In this Perspective, we first review and summarize rational synthesis methods and advanced characterization techniques for SAA nanoparticle catalysts. We then emphasize the extensive applications of SAAs in a range of electrocatalytic reactions, including fuel cell reactions, water splitting, and carbon dioxide and nitrate reductions. Finally, we provide insights into existing challenges and prospects associated with the controlled synthesis, characterization, and design of SAA catalysts.

Identification of characteristic flavor quality of ceramic-pot sealed meat after reheating based on HS-GC-IMS, bionic sensory combined chemometrics.

This study investigated the impacts of microwave reheating (MR), boil reheating (BR), and steam reheating (SR) on the flavor profile of Ceramic-Pot Sealed Meat (CPSM). Electronic nose and tongue revealed that the microwaving was superior in preserving the original olfactory and gustatory profiles of CPSM compared to the other methods. Headspace- Gas chromatography- ion mobility spectrometry (HS-GC-IMS) detected 48 compounds, encompassing 15 alcohols, 11 aldehydes, 9 ketones, 7 esters, 2 alkenes, and 2 others, 1 acid. Spectral and clustering analysis revealed a significant rise in the content of Warmed-over flavor compounds after boil reheating, culminating in pronounced flavor distortion and a decline in sensory scores. Relative odor activity value (ROAV) and chemometrics identified nine substances as the principal flavor compounds responsible to flavor distortion. In conclusion, all reheating methods induce changes in the original flavor characteristics profiles of CPSM. However, microwave reheating offers superior preservation of the flavor characteristics of CPSM.

Softening the tumor matrix through cholesterol depletion breaks the physical barrier for enhanced antitumor therapy.

The tumor develops defense tactics, including conversing the mechanical characteristics of tumor cells and their surrounding environment. A recent study reported that cholesterol depletion stiffens tumor cells, which could enhance adaptive T-cell immunotherapy. However, it remains unclear whether reducing the cholesterol in tumor cells contributes to re-educating the stiff tumor matrix, which serves as a physical barrier against drug penetration. Herein, we found that depleting cholesterol from tumor cells can demolish the intratumor physical barrier by disrupting the mechanical signal transduction between tumor cells and the extracellular matrix through the destruction of lipid rafts. This disruption allows nanoparticles (H/S@hNP) to penetrate deeply, resulting in improved photodynamic treatment. Our research also indicates that cholesterol depletion can inhibit the epithelial-mesenchymal transition and repolarize tumor-associated macrophages from M2 to M1, demonstrating the essential role of cholesterol in tumor progression. Overall, this study reveals that a cholesterol-depleted, softened tumor matrix reduces the difficulty of drug penetration, leading to enhanced antitumor therapeutics.