Environmental permittivity-asymmetric BIC metasurfaces with electrical reconfigurability.

Achieving precise spectral and temporal light manipulation at the nanoscale remains a critical challenge in nanophotonics. While photonic bound states in the continuum (BICs) have emerged as a powerful means of controlling light, their reliance on geometrical symmetry breaking for obtaining tailored resonances makes them highly susceptible to fabrication imperfections, and their generally fixed asymmetry factor fundamentally limits applications in reconfigurable metasurfaces. Here, we introduce the concept of environmental symmetry breaking by embedding identical resonators into a surrounding medium with carefully placed regions of contrasting refractive indexes, activating permittivity-driven quasi-BIC resonances (ε-qBICs) without altering the underlying resonator geometry and unlocking an additional degree of freedom for light manipulation through active tuning of the surrounding dielectric environment. We demonstrate this concept by integrating polyaniline (PANI), an electro-optically active polymer, to achieve electrically reconfigurable ε-qBICs. This integration not only demonstrates rapid switching speeds and exceptional durability but also boosts the system's optical response to environmental perturbations. Our strategy significantly expands the capabilities of resonant light manipulation through permittivity modulation, opening avenues for on-chip optical devices, advanced sensing, and beyond.

Pressure-Induced Changes in the Phase Distribution and Carrier Dynamics of Quasi-Two-Dimensional Ruddlesden-Popper Perovskites.

Quasi-two-dimensional (quasi-2D) perovskites hold significant potential for diverse design strategies due to their tunable structures, exceptional optical properties, and environmental stability. Due to the complexity of the structure and carrier dynamics, characterization methods such as photoluminescence and absorption spectroscopy can observe but cannot precisely distinguish or identify the phase distribution within quasi-2D perovskite films or correlate phases with carrier dynamics. In this study, we used pressure to modulate the intralayer and interlayer structures of (PEA)2Csn-1PbnBr3n+1 quasi-2D perovskite films, investigating charge carrier dynamics. Steady-state spectroscopy revealed phase transitions at 1.62, 3, and 8 GPa, with free excitons transforming into self-trapped excitons after 8 GPa. Transient absorption spectroscopy elucidated the structural evolution, energy transfer, and pressure-induced transition mechanisms. The results demonstrate that combining pressure and spectroscopy enables the precise identification of phase distribution and pressure response ranges and reveals photophysical mechanisms, providing new insights for optimizing optoelectronic materials.

CPT1A-IL-10-mediated macrophage metabolic and phenotypic alterations ameliorate acute lung injury.

BACKGROUND: Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a common acute respiratory failure due to diffuse pulmonary inflammation and oedema. Elaborate regulation of macrophage activation is essential for managing this inflammatory process and maintaining tissue homeostasis. In the past decades, metabolic reprogramming of macrophages has emerged as a predominant role in modulating their biology and function. Here, we observed reduced expression of carnitine palmitoyltransferase 1A (CPT1A), a key rate-limiting enzyme of fatty acid oxidation (FAO), in macrophages of lipopolysaccharide (LPS)-induced ALI mouse model. We assume that CPT1A and its regulated FAO is involved in the regulation of macrophage polarization, which could be positive regulated by interleukin-10 (IL-10). METHODS: After nasal inhalation rIL-10 and/or LPS, wild type (WT), IL-10-/-, Cre-CPT1Afl/fl and Cre+CPT1Afl/fl mice were sacrificed to harvest bronchoalveolar lavage fluid, blood serum and lungs to examine cell infiltration, cytokine production, lung injury severity and IHC. Bone marrow-derived macrophages (BMDMs) were extracted from mice and stimulated by exogenous rIL-10 and/or LPS. The qRT-PCR, Seahorse XFe96 and FAO metabolite related kits were used to test the glycolysis and FAO level in BMDMs. Immunoblotting assay, confocal microscopy and fluorescence microplate were used to test macrophage polarization as well as mitochondrial structure and function damage. RESULTS: In in vivo experiments, we found that mice lacking CPT1A or IL-10 produced an aggravate inflammatory response to LPS stimulation. However, the addition of rIL-10 could alleviate the pulmonary inflammation in mice effectively. IHC results showed that IL-10 expression in lung macrophage decreased dramatically in Cre+CPT1Afl/fl mice. The in vitro experiments showed Cre+CPT1Afl/fl and IL-10-/- BMDMs became more "glycolytic", but less "FAO" when subjected to external attacks. However, the supplementation of rIL-10 into macrophages showed reverse effect. CPT1A and IL-10 can drive the polarization of BMDM from M1 phenotype to M2 phenotype, and CPT1A-IL-10 axis is also involved in the process of maintaining mitochondrial homeostasis. CONCLUSIONS: CPT1A modulated metabolic reprogramming and polarisation of macrophage under LPS stimulation. The protective effects of CPT1A may be partly attributed to the induction of IL-10/IL-10 receptor expression.

Beware of Resistance to 2nd-generation Integrase Inhibitors: A Systematic Meta-analysis of HIV-1 Integrase Inhibitors Resistance and Drug Resistance Mutations.

OBJECTIVE: Assessing the prevalence of resistance and drug resistance mutations (DRMs) in HIV/AIDS patients towards integrase strand transfer inhibitors (INSTIs), particularly the 2nd-generation INSTIs, provides evidence for rational clinical drug use. METHODS: A systematic search was conducted on five databases to identify relevant literature reporting original data on INSTIs resistance. Meta-analyses, cumulative meta-analyses, subgroup analyses, and meta-regression analyses were performed using selected models based on the results of heterogeneity tests. RESULTS: A total of 81 studies were included in this analysis. The prevalence of pre-treatment drug resistance (PDR) to 1st-generation INSTIs and 2nd-generation INSTIs were 0.41% (95% CI: 0.19%-0.70%) and 0.04% (95% CI: 0.00%-0.13%), respectively; and the prevalence of acquired drug resistance (ADR) were 7.60% (95% CI: 3.54%-12.92%) and 4.93% (95% CI: 1.78%-9.36%), respectively, and ADR showed an increasing and then decreasing time trend. The results of subgroup analyses showed differences in ADR to 2nd-generation INSTIs between regions and economic levels, with the highest ADR of 12.83% (95% CI: 3.24%-27.17%) in the European region. DRMs varied among HIV patients and reduced drug sensitivity to varying degrees. CONCLUSION: The prevalence of PDR and DRMs in 2nd-generation INSTIs is currently low, but as the use of DTG-based ART expands, population-level drug resistance monitoring and individual-level genetic testing should be strengthened in order to maximize treatment efficacy. Additionally, attention should be paid to ADR of INSTIs to provide personalized treatments for HIV-infected patients.

Plant leaf disease recognition based on improved SinGAN and improved ResNet34.

The identification of plant leaf diseases is crucial in precision agriculture, playing a pivotal role in advancing the modernization of agriculture. Timely detection and diagnosis of leaf diseases for preventive measures significantly contribute to enhancing both the quantity and quality of agricultural products, thereby fostering the in-depth development of precision agriculture. However, despite the rapid development of research on plant leaf disease identification, it still faces challenges such as insufficient agricultural datasets and the problem of deep learning-based disease identification models having numerous training parameters and insufficient accuracy. This paper proposes a plant leaf disease identification method based on improved SinGAN and improved ResNet34 to address the aforementioned issues. Firstly, an improved SinGAN called Reconstruction-Based Single Image Generation Network (ReSinGN) is proposed for image enhancement. This network accelerates model training speed by using an autoencoder to replace the GAN in the SinGAN and incorporates a Convolutional Block Attention Module (CBAM) into the autoencoder to more accurately capture important features and structural information in the images. Random pixel Shuffling are introduced in ReSinGN to enable the model to learn richer data representations, further enhancing the quality of generated images. Secondly, an improved ResNet34 is proposed for plant leaf disease identification. This involves adding CBAM modules to the ResNet34 to alleviate the limitations of parameter sharing, replacing the ReLU activation function with LeakyReLU activation function to address the problem of neuron death, and utilizing transfer learning-based training methods to accelerate network training speed. This paper takes tomato leaf diseases as the experimental subject, and the experimental results demonstrate that: (1) ReSinGN generates high-quality images at least 44.6 times faster in training speed compared to SinGAN. (2) The Tenengrad score of images generated by the ReSinGN model is 67.3, which is improved by 30.2 compared to the SinGAN, resulting in clearer images. (3) ReSinGN model with random pixel Shuffling outperforms SinGAN in both image clarity and distortion, achieving the optimal balance between image clarity and distortion. (4) The improved ResNet34 achieved an average recognition accuracy, recognition precision, recognition accuracy (redundant as it's similar to precision), recall, and F1 score of 98.57, 96.57, 98.68, 97.7, and 98.17%, respectively, for tomato leaf disease identification. Compared to the original ResNet34, this represents enhancements of 3.65, 4.66, 0.88, 4.1, and 2.47%, respectively.

Diverse associations between pancreatic intra-, inter-lobular fat and the development of type 2 diabetes in overweight or obese patients.

Pancreatic fat is associated with obesity and type 2 diabetes mellitus (T2DM); however, the relationship between different types of pancreatic fat and diabetes status remains unclear. Therefore, we aimed to determine the potential of different types of pancreatic fat accumulation as a risk factor for T2DM in overweight or obese patients. In total, 104 overweight or obese patients were recruited from January 2020 to December 2022. The patients were divided into three groups: normal glucose tolerance (NGT), impaired fasting glucose or glucose tolerance (IFG/IGT), and T2DM. mDixon magnetic resonance imaging (MRI) was used to detect pancreatic fat in all three groups of patients. The pancreatic head fat (PHF), body fat (PBF), and tail fat (PTF) in the IFG/IGT group were 21, 20, and 31% more than those in the NGT group, respectively. PHF, PBF, and PTF were positively associated with glucose metabolic dysfunction markers in the NGT group, and inter-lobular fat volume (IFV) was positively associated with these markers in the IFG/IGT group. The areas under the receiver operating characteristic curves for PHF, PBF, and PTF (used to evaluate their diagnostic potential for glucose metabolic dysfunction) were 0.73, 0.73, and 0.78, respectively, while those for total pancreatic volume (TPV), pancreatic parenchymal volume, IFV, and IFV/TPV were 0.67, 0.67, 0.66, and 0.66, respectively. These results indicate that intra-lobular pancreatic fat, including PHF, PTF, and PBF, may be a potential independent risk factor for the development of T2DM. Additionally, IFV exacerbates glucose metabolic dysfunction. Intra-lobular pancreatic fat indices were better than IFV for the diagnosis of glucose metabolic dysfunction.

A prognostic model for anoikis-related genes in pancreatic cancer.

Anoikis, a distinct form of programmed cell death, is crucial for both organismal development and maintaining tissue equilibrium. Its role extends to the proliferation and progression of cancer cells. This study aimed to establish an anoikis-related prognostic model to predict the prognosis of pancreatic cancer (PC) patients. Gene expression data and patient clinical profiles were sourced from The Cancer Genome Atlas (TCGA-PAAD: Pancreatic Adenocarcinoma) and the International Cancer Genome Consortium (ICGC-PACA: Pancreatic Ductal Adenocarcinoma). Non-cancerous pancreatic tissue gene expression data were obtained from the Genotype-Tissue Expression (GTEx) project. The R package was used to construct anoikis-related PC prognostic models, which were later validated with the ICGC-PACA database. Survival analyses demonstrated a poorer prognosis for patients in the high-risk group, consistent across both TCGA-PAAD and ICGC-PACA datasets. A nomogram was designed as a predictive tool to estimate patient mortality. The study also analyzed tumor mutations and immune infiltration across various risk groups, uncovering notable differences in tumor mutation patterns and immune landscapes between high- and low-risk groups. In conclusion, this research successfully developed a prognostic model centered on anoikis-related genes, offering a novel tool for predicting the clinical trajectory of PC patients.

Importance of iron complexation and floc formation towards phosphonate removal with Fe-electrocoagulation.

Phosphonates are widely used scale inhibitors, but the residual phosphonates in drainage are challenging to remove because of their chelating capacity and resistance to biodegradation. Here, we reported a highly efficient and robust Fe-electrocoagulation (Fe-EC) system for phosphonate removal. Surprisingly, we found for the first time that phosphonates like NTMP were more efficiently removed under anoxic conditions (80% of total soluble phosphorus (TSP) in 4 min) than oxic conditions (0% of TSP within 6 min) in NaCl solution. A similar phenomenon was observed when other phosphonates, such as EDTMP and DTPMP, were removed, highlighting the importance of iron complexation and floc formation toward phosphonate removal with Fe-EC. We also showed that the removal efficiency of NTMP by electrochemically in-situ formed flocs (97%) was much higher than post-adsorption systems (ex-situ, 40%), revealing that the growth of flocs consumed the active site for NTMP adsorption. Beyond the removal of TSP, 10 % of NTMP-P was also degraded after the electrolysis phase, evidenced by the evolution of phosphate-P. However, this did not happen in anoxic or chemical coagulation processes, which confirms the formation of reactive oxygen species via Fe(II) oxidation in the oxic Fe-EC system. The primary removal mechanism of phosphonates is due to their complexation with iron (hydr)oxide generated in the Fe-EC system by forming a Fe-O-P bond. Encouragingly, the Fe-EC system exhibits comparable or even better performance in treating phosphonate-laden wastewater (i.e., cooling water). Our preliminary cost calculation suggests the proposed system (€ 0.009/m3) has a much lower OPEX under oxic conditions than existing approaches. This study sheds light on the removal mechanism of phosphonate and the treatment of phosphonate-laden wastewater by playing with the iron complexion and flocs formation in classical Fe-EC systems.

Integrative analysis identifies region- and sex-specific gene networks and Mef2c as a mediator of anxiety-like behavior.

The molecular mechanisms underlying multi-brain region origins and sexual dimorphism of anxiety remain unclear. Here, we leverage large-scale transcriptomics from seven brain regions in mouse models of anxiety and extensive experiments to dissect brain-region- and sex-specific gene networks. We identify 4,840 genes with sex-specific expression alterations across seven brain regions, organized into ten network modules with sex-biased expression patterns. Modular analysis prioritizes 86 sex-specific mediators of anxiety susceptibility, including myocyte-specific enhancer factor 2c (Mef2c) in the CA3 region of male mice. Mef2c expression is decreased in the pyramidal neurons (PyNs) of susceptible male mice. Up-regulating Mef2c in CA3 PyNs significantly alleviates anxiety-like behavior, whereas down-regulating Mef2c induces anxiety-like behavior in male mice. The anxiolytic effect of Mef2c up-regulation is associated with enhanced neuronal excitability and synaptic transmission. In summary, this study uncovers brain-region- and sex-specific networks and identifies Mef2c in CA3 PyNs as a critical mediator of anxiety in male mice.

Cancer cell membrane-camouflaged paclitaxel/PLGA nanoparticles for targeted therapy against lung cancer.

Paclitaxel (PTX) is a first-line drug for the treatment of lung cancer, but its targeting and therapeutic effect are unsatisfactory. Herein, lung cancer cell (A549) membrane biomimetic PTX-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles (AM@PTX-NPs) were constructed to eliminate the shortcomings of PTX. The AM@PTX-NPs were successfully prepared with a high drug loading efficiency (10.90±0.06 %). Moreover, transmission electron microscopy, SDS-PAGE, and western blotting proved that AM@PTX-NPs were spherical nanoparticles camouflaged by the A549 cell membrane. Both in vitro and in vivo assays revealed that the AM@PTX-NPs displayed outstanding targeting capacity due to A549 membrane modification. The cytotoxicity experiment showed that the developed biomimetic formulation was able to effectively reduce the proliferation of A549 cells. Moreover, AM@PTX-NPs exhibited a significant tumor growth inhibition rate (73.00 %) with good safety in the tumor-bearing mice, which was higher than that of the PTX-NPs without A549 membrane coating (37.39 %). Overall, the constructed bioinspired vector could provide a novel platform for the PTX delivery and demonstrated a promising strategy for the targeted cancer treatment.

Rational Design of a Flavoenzyme for Aerobic Nicotine Catabolism.

Enzymatic therapy with nicotine-degrading enzyme is a new strategy in treating nicotine addiction, which can reduce nicotine concentrations and weaken withdrawal in the rat model. However, when O2 is used as the electron acceptor, no satisfactory performance has been achieved with one of the most commonly studied and efficient nicotine-catabolizing enzymes, NicA2. To obtain more efficient nicotine-degrading enzyme, we rationally designed and engineered a flavoenzyme Pnao, which shares high structural similarity with NicA2 (RMSD = 1.143 Å) and efficiently catalyze pseudooxynicotine into 3-succinoyl-semialdehyde pyridine using O2. Through amino acid alterations with NicA2, five Pnao mutants were generated, which can degrade nicotine in Tris-HCl buffer and retained catabolic activity on its natural substrate. Nicotine-1'-N-oxide was identified as one of the reaction products. Four of the derivative mutants showed activity in rat serum and Trp220 and Asn224 were found critical for enzyme specificity. Our findings offer a novel avenue for research into aerobic nicotine catabolism and provides a promising method of generating additional nicotine-catalytic enzymes.

Meta-omics assisted microbial gene and strain resources mining in contaminant environment.

Human activities have led to the release of various environmental pollutants, triggering ecological challenges. In situ, microbial communities in these contaminated environments are usually assumed to possess the potential capacity of pollutant degradation. However, the majority of genes and microorganisms in these environments remain uncharacterized and uncultured. The advent of meta-omics provided culture-independent solutions for exploring the functional genes and microorganisms within complex microbial communities. In this review, we highlight the applications and methodologies of meta-omics in uncovering of genes and microbes from contaminated environments. These findings may assist in future bioremediation research.

Goos-Hänchen shift in cryogenic defect photonic crystals composed of superconductor HgBa2Ca2Cu3O8+δ.

We explore theoretically Goos-Hänchen (GH) shift around the defect mode in superconducting defective photonic crystals (PCs) in cryogenic environment. The defective PCs are constructed by alternating semiconductors and superconductors. A defect mode arises in the photonic bandgap and sensitively depends on environment temperature and hydrostatic pressure. Reflection and transmission coefficient phases make an abruptly jump at the defect mode and giant GH shifts have been achieved around this mode. The maximum GH shift can get as high as 103λ (incident wavelength), which could be modulated by the values of temperature and hydrostatic pressure. This study may be utilized for pressure- or temperature-sensors in cryogenic environment.

Biomimetic platelet-like nanoparticles enhance targeted hepatocellular carcinoma therapy.

Curcumin (CUR) is a promising natural product for hepatocellular carcinoma (HCC) therapy. However, its clinical application has been limited by some issues such as rapid clearance and inadequate tumor accumulation. To address these drawbacks, we developed platelet membrane-coated CUR-loaded PLGA nanoparticles (PCPNPs). In this work, due to the bioinspired strategy, the PCPNPs exhibited immune evasion, prolonged circulation, and improved accumulation at tumor sites compared to the traditional CUR formulation. The superior tumor targeting of PCPNPs was likely due to the interactions between platelet P-selectin and tumoral CD44. Furthermore, both in vitro and in vivo assays revealed that the PCPNPs showed outstanding anticancer efficacy without obvious toxicity. Therefore, PCPNPs represent a biosafe and promising anti-tumor strategy, overcoming the limitations associated with CUR. These findings not only contribute to the advancement of natural compound nano-formulation but also open new avenues for targeted cancer treatment.

Performance Study of High-Speed Permanent Magnet Synchronous Motor with Amorphous Alloy Considering Temperature Effect.

Because the magnetic properties of an amorphous alloy (AA) obviously change with the change of temperature, a finite element simulation method for a motor, considering the effect of temperature, is proposed in this paper. In the early design stage of the high-speed permanent magnet synchronous motor (PMSM), the simulation of motor performance is mainly based on the magnetic performance test data at room temperature provided by the material's manufacturer. However, the influence of the temperature rise during the actual operation of the motor will lead to large errors between the simulation results and the measured results. Therefore, it is of great practical significance to measure the magnetic properties of the AA at different temperatures and use them for simulation purposes. In this paper, the magnetization characteristics and iron loss characteristics of the AA and silicon steel (ST100) used for comparison are measured at different temperatures, and the iron loss separation of the two materials at different temperatures is completed, and the hysteresis loss coefficient and eddy current loss coefficient at different temperatures are obtained. On this basis, the performance simulation of a motor model is carried out. The more accurate simulation method proposed in this paper can provide a reference for the design of AA motors in industry.

Association Between Composite Dietary Antioxidant Index and the Risk of Endometriosis-Related Rheumatoid Arthritis in Women of Childbearing Age: A Cross-Sectional Study Based on the National Health and Nutrition Examination Survey Database.

Purpose: To evaluate the association between Composite Dietary Antioxidant Index (CDAI) and the risk of endometriosis (EM)-related rheumatoid arthritis (RA) in women of childbearing age. Methods: Using the data from the National Health and Nutrition Examination Survey database, this cross-sectional study included women of childbearing age. The CDAI was obtained by summing the standardized Z-values of the dietary intakes. EM was diagnosed based on a questionnaire-based survey. The outcome of this study was the presence of RA, which was defined by a questionnaire. The associations of CDAI and EM with the risk of RA were determined using weighted logistic analysis. Additive interaction was evaluated using the relative excess risk due to interaction (RERI), the attributable proportion due to interaction (AP), and the synergy index (S). Results: In total, 3803 patients were included, of which 74 patients (1.99%) were with RA. A lower CDAI [odds ratio (OR): 1.85, 95% confidence interval (CI): 1.12 to 3.04, P= 0.015] and the presence of EM (OR: 3.05, 95% CI: 1.19 to 7.81, P= 0.023) was associated with the risk of RA. The result demonstrated an additive interaction of a lower CDAI and the presence of EM on the risk of RA (OR: 6.19, 95% CI: 2.33 to 16.43, P <0.001, P of trend =0.007). Nevertheless, there was no significant additive interaction after being assessed by the RERI, AP, and S. However, a joint effect of a lower CDAI and EM on the risk of RA (OR: 3.94, 95% CI: 1.35 to 11.51, P= 0.013) was observed. Conclusion: Our study identified EM, and lower CDAI, was related to the risk of RA. Lower CDAI score was also associated with the risk of EM-related RA. This study indicates the importance of antioxidant intake in daily diet for the management of EM-related RA.

Blocking cGAS-STING pathway promotes post-stroke functional recovery in an extended treatment window via facilitating remyelination.

BACKGROUND: Ischemic stroke is a major cause of worldwide death and disability, with recombinant tissue plasminogen activator being the sole effective treatment, albeit with a limited treatment window. The cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING) pathway is emerging as the major DNA-sensing pathway to invoke immune responses in neuroinflammatory disorders. METHODS: By performing a series of neurobehavioral assessments, electrophysiological analysis, high-throughput sequencing, and cell-based assays based on the transient middle cerebral artery occlusion (tMCAO) mouse stroke model, we examined the effects and underlying mechanisms of genetic and pharmacological inhibition of the cGAS-STING pathway on long-term post-stroke neurological functional outcomes. FINDINGS: Blocking the cGAS-STING pathway, even 3 days after tMCAO, significantly promoted functional recovery in terms of white matter structural and functional integrity as well as sensorimotor and cognitive functions. Mechanistically, the neuroprotective effects via inhibiting the cGAS-STING pathway were contributed not only by inflammation repression at the early stage of tMCAO but also by modifying the cell state of phagocytes to facilitate remyelination at the sub-acute phase. The activation of the cGAS-STING pathway significantly impeded post-stroke remyelination through restraining myelin debris uptake and degradation and hindering oligodendrocyte differentiation and maturation. CONCLUSIONS: Manipulating the cGAS-STING pathway has an extended treatment window in promoting long-term post-stroke functional recovery via facilitating remyelination in a mouse stroke model. Our results highlight the roles of the cGAS-STING pathway in aggregating stroke pathology and propose a new way for improving functional recovery after ischemic stroke. FUNDING: This work was primarily funded by the National Key R&D Program of China.

Membrane Fusion Liposomes Deliver Antifibrotic and Chemotherapeutic Drugs Sequentially to Enhance Tumor Treatment Efficacy by Reshaping Tumor Microenvironment.

The intricate tumor microenvironment in triple-negative breast cancer (TNBC) hampers chemotherapy and immunotherapy efficacy due to dense extracellular matrix (ECM) by tumor-associated fibroblasts (TAFs). Nanoparticle-based therapies, especially "all-in-one" nanoparticles, have shown great potential in combined drug delivery strategies to reshape the tumor microenvironment and enhance therapeutic efficiency. However, these "all-in-one" nanoparticles suffer from limitations in targeting different target cells, uncontrollable dosing ratio, and disregarding the impact of delivery schedules. This study prepared cell membrane fusion liposomes (TAFsomes and CCMsomes) to load FDA-approved antifibrotic drug pirfenidone (PFD/TAFsomes) and antitumor drug doxorubicin (DOX/CCMsomes). These liposomes can specifically target TAFs cells and tumor cells, and combined administration can effectively inhibit TAFs activity, reshape the tumor microenvironment (TME), and significantly enhance the tumor chemotherapy efficacy. Combined drug delivery defeats "all-in-one" liposomes (DOX/PFD/Liposomes, DOX/PFD/TAFsomes, and DOX/PFD/CCMsomes) by flexibly adjusting the drug delivery ratio. Moreover, an asynchronous delivery strategy that optimizes the administration schedule not only further improves the therapeutic effect, but also amplifies the effectiveness of α-PD-L1 immunotherapy by modulating the tumor immune microenvironment. This delivery strategy provides a personalized treatment approach with clinical translation potential, providing new ideas for enhancing the therapeutic effect against solid tumors such as TNBC.

Effects of Storage in an Active and Spontaneous Controlled O2/CO2 Atmosphere on Volatile Flavor Components and the Microbiome of Truffles.

This study explored the potential to improve the storage quality and prolong the shelf life of truffles by storing them in a modified atmosphere fresh-keeping box with sealed gas components of Active Modified Atmosphere Packaging (AMAP, 40% O2 + 60% CO2) at 4 °C. During the storage period, a total of 63 volatile components in 10 categories were detected, with aldehydes being the most abundant and the relative content of ethers being the highest. The relative odor activity value and principal component analysis revealed that isovaleraldehyde, 1-octen-3-ol, 1-octen-3-one, and dimethyl sulfide were the characteristic flavor components of fresh truffles. However, 3-methylthiopropionaldehyde and (E, E)-2,4-nonadienal were the components that caused the deterioration of truffle flavor and could potentially serve as markers of truffle decay characteristics. 16S rDNA high-throughput sequencing showed that Leuconostoc and Lactococcus were dominant in the truffle samples stored for 14 days, but the abundance of putrefactive pathogenic bacteria showed an increasing trend in the truffle samples stored for 28 days. During the whole storage period, the common fungi detected in the different treatment groups were Candida and Aspergillus. The relative abundance of the former decreased, while the relative abundance of the latter decreased initially and then increased. The correlation between volatile components and the microbial flora was further analyzed, which indicated that Lactococcus and Lactobacillus had the same contributions to the same flavor, while Pseudomonas and Glutamicibacter had the opposite contributions to the same flavor. The results provide a reference for the storage and preservation of truffles.