Association between Gene Polymorphisms and SNP-SNP Interactions of the Matrix Metalloproteinase 2 Signaling Pathway and the Risk of Vascular Senescence.

Objective: This study aimed to explore the association of single nucleotide polymorphisms (SNP) in the matrix metalloproteinase 2 (MMP-2) signaling pathway and the risk of vascular senescence (VS). Methods: In this cross-sectional study, between May and November 2022, peripheral venous blood of 151 VS patients (case group) and 233 volunteers (control group) were collected. Fourteen SNPs were identified in five genes encoding the components of the MMP-2 signaling pathway, assessed through carotid-femoral pulse wave velocity (cfPWV), and analyzed using multivariate logistic regression. The multigene influence on the risk of VS was assessed using multifactor dimensionality reduction (MDR) and generalized multifactor dimensionality regression (GMDR) modeling. Results: Within the multivariate logistic regression models, four SNPs were screened to have significant associations with VS: chemokine (C-C motif) ligand 2 (CCL2) rs4586, MMP2 rs14070, MMP2 rs7201, and MMP2 rs1053605. Carriers of the T/C genotype of MMP2 rs14070 had a 2.17-fold increased risk of developing VS compared with those of the C/C genotype, and those of the T/T genotype had a 19.375-fold increased risk. CCL2 rs4586 and MMP-2 rs14070 exhibited the most significant interactions. Conclusion: CCL2 rs4586, MMP-2 rs14070, MMP-2 rs7201, and MMP-2 rs1053605 polymorphisms were significantly associated with the risk of VS.

A radiomics signature derived from CT imaging to predict MSI status and immunotherapy outcomes in gastric cancer: a multi-cohort study.

BACKGROUND: Accurate microsatellite instability (MSI) testing is essential for identifying gastric cancer (GC) patients eligible for immunotherapy. We aimed to develop and validate a CT-based radiomics signature to predict MSI and immunotherapy outcomes in GC. METHODS: This retrospective multicohort study included a total of 457 GC patients from two independent medical centers in China and The Cancer Imaging Archive (TCIA) databases. The primary cohort (n = 201, center 1, 2017-2022), was used for signature development via Least Absolute Shrinkage and Selection Operator (LASSO) and logistic regression analysis. Two independent immunotherapy cohorts, one from center 1 (n = 184, 2018-2021) and another from center 2 (n = 43, 2020-2021), were utilized to assess the signature's association with immunotherapy response and survival. Diagnostic efficiency was evaluated using the area under the receiver operating characteristic curve (AUC), and survival outcomes were analyzed via the Kaplan-Meier method. The TCIA cohort (n = 29) was included to evaluate the immune infiltration landscape of the radiomics signature subgroups using both CT images and mRNA sequencing data. RESULTS: Nine radiomics features were identified for signature development, exhibiting excellent discriminative performance in both the training (AUC: 0.851, 95%CI: 0.782, 0.919) and validation cohorts (AUC: 0.816, 95%CI: 0.706, 0.926). The radscore, calculated using the signature, demonstrated strong predictive abilities for objective response in immunotherapy cohorts (AUC: 0.734, 95%CI: 0.662, 0.806; AUC: 0.724, 95%CI: 0.572, 0.877). Additionally, the radscore showed a significant association with PFS and OS, with GC patients with a low radscore experiencing a significant survival benefit from immunotherapy. Immune infiltration analysis revealed significantly higher levels of CD8 + T cells, activated CD4 + B cells, and TNFRSF18 expression in the low radscore group, while the high radscore group exhibited higher levels of T cells regulatory and HHLA2 expression. CONCLUSION: This study developed a robust radiomics signature with the potential to serve as a non-invasive biomarker for GC's MSI status and immunotherapy response, demonstrating notable links to post-immunotherapy PFS and OS. Additionally, distinct immune profiles were observed between low and high radscore groups, highlighting their potential clinical implications.

Identification of immune-associated biomarker for predicting lung adenocarcinoma: bioinformatics analysis and experiment verification of PTK6.

BACKGROUND: Abnormal expression of protein tyrosine kinase 6 (PTK6) has been proven to be involved in the development of gynecological tumors. However, its immune-related carcinogenic mechanism in other tumors remains unclear. OBJECTIVE: The aim of this study was to identify PTK6 as a novel prognostic biomarker in pan-cancer, especially in lung adenocarcinoma (LUAD), which is correlated with immune infiltration, and to clarify its clinicopathological and prognostic significance. METHODS: The prognostic value and immune relevance of PTK6 were investigated by using bio-informatics in this study. PTK6 expression was validated in vitro experiments (lung cancer cell lines PC9, NCI-H1975, and HCC827; human normal lung epithelial cells BEAS-2B). Western blot (WB) revealed the PTK6 protein expression in lung cancer cell lines. PTK6 expression was inhibited by Tilfrinib. Colony formation and the Cell Counting Kit-8 (CCK-8) assay were used to detect cell proliferation. The wound healing and trans-well were performed to analyze the cell migration capacity. Then flow cytometry was conducted to evaluate the cell apoptosis. Eventually, the relationship between PTK6 and immune checkpoints was examined. WB was used to estimate the PD-L1 expression at different Tilfrinib doses. RESULTS: PTK6 was an independent predictive factor for LUAD and was substantially expressed in LUAD. Pathological stage was significantly correlated with increased PTK6 expression. In accordance with survival analysis, poor survival rate in LUAD was associated with a high expression level of PTK6. Functional enrichment of the cell cycle and TGF-ß signaling pathway was demonstrated by KEGG and GSEA analysis. Moreover, PTK6 expression considerably associated with immune infiltration in LUAD, as determined by immune analysis. Thus, the result of vitro experiments indicated that cell proliferation and migration were inhibited by the elimination of PTK6. Additionally, PTK6 suppression induced cell apoptosis. Obviously, PD-L1 protein expression level up-regulated while PTK6 was suppressed. CONCLUSION: PTK6 has predictive value for LUAD prognosis, and could up regulated PD-L1.

ELODI: Ensemble Logit Difference Inhibition for Positive-Congruent Training.

Negative flips are errors introduced in a classification system when a legacy model is updated. Existing methods to reduce the negative flip rate (NFR) either do so at the expense of overall accuracy by forcing a new model to imitate the old models, or use ensembles, which multiply inference cost prohibitively. We analyze the role of ensembles in reducing NFR and observe that they remove negative flips that are typically not close to the decision boundary, but often exhibit large deviations in the distance among their logits. Based on the observation, we present a method, called Ensemble Logit Difference Inhibition (ELODI), to train a classification system that achieves paragon performance in both error rate and NFR, at the inference cost of a single model. The method distills a homogeneous ensemble to a single student model which is used to update the classification system. ELODI also introduces a generalized distillation objective, Logit Difference Inhibition (LDI), which only penalizes the logit difference of a subset of classes with the highest logit values. On multiple image classification benchmarks, model updates with ELODI demonstrate superior accuracy retention and NFR reduction.

Characterization of the Structure and Physicochemical Properties of Soluble Dietary Fiber from Peanut Shells Prepared by Pulsed Electric Fields with Three-Phase Partitioning.

This study evaluated the impact of pulsed electric fields (PEFs) combined with three-phase partitioning (TPP) extraction methods on the physicochemical properties, functional properties, and structural characterization of the soluble dietary fiber (SDF) derived from peanut shells (PS). The findings of this study indicated that the application of a PEF-TPP treatment leads to a notable improvement in both the extraction yield and purity of SDF. Consequently, the PEF-TPP treatment resulted in the formation of more intricate and permeable structures, a decrease in molecular weight, and an increase in thermal stability compared to SDFs without TPP treatment. An analysis revealed that the PEF-TPP method resulted in an increase in the levels of arabinose and galacturonic acid, leading to enhanced antioxidant capacities. Specifically, the IC50 values were lower in SDFs which underwent PEF-TPP (4.42 for DPPH and 5.07 mg/mL for ABTS) compared to those precipitated with 40% alcohol (5.54 mg/mL for DPPH, 5.56 mg/mL for ABTS) and PEF75 (6.60 mg/mL for DPPH, 7.61 mg/mL for ABTS), respectively. Notably, the SDFs which underwent PEF-TPP demonstrated the highest water- and oil-holding capacity, swelling capacity, emulsifying activity, emulsion stability, glucose adsorption, pancreatic lipase inhibition, cholesterol adsorption, nitric ion adsorption capacity, and the least gelation concentration. Based on the synthesis scores obtained through PCA (0.536 > -0.030 > -0.33), which indicated that SDFs which underwent PEF-TPP exhibited the highest level of quality, the findings indicate that PEF-TPP exhibits potential and promise as a method for preparing SDFs.

Erratum to: Molecular dynamics simulation reveals DNA-specific recognition mechanism via c-Myb in pseudo-palindromic consensus of mim-1 promoter.

The original version of this article (Weng et al., 2023) unfortunately contained a mistake. In Acknowledgments, the number (No. 226-2022-00213) of the Fundamental Research Funds for the Central Universities is wrong. The correct number should be No. 2022FZZX01-33.

Self-assembly of stabilized droplets from liquid-liquid phase separation for higher-order structures and functions.

Dynamic microscale droplets produced by liquid-liquid phase separation (LLPS) have emerged as appealing biomaterials due to their remarkable features. However, the instability of droplets limits the construction of population-level structures with collective behaviors. Here we first provide a brief background of droplets in the context of materials properties. Subsequently, we discuss current strategies for stabilizing droplets including physical separation and chemical modulation. We also discuss the recent development of LLPS droplets for various applications such as synthetic cells and biomedical materials. Finally, we give insights on how stabilized droplets can self-assemble into higher-order structures displaying coordinated functions to fully exploit their potentials in bottom-up synthetic biology and biomedical applications.

H3K4me3-Mediated FOXJ2/SLAMF8 Axis Aggravates Thrombosis and Inflammation in ß2GPI/Anti-ß2GPI-Treated Monocytes.

Antiphospholipid syndrome (APS) is characterized by thrombus formation, poor pregnancy outcomes, and a proinflammatory response. H3K4me3-related monocytes activation are key regulators of APS pathogenesis. Therefore, H3K4me3 CUT&Tag and ATAC-seq are performed to examine the epigenetic profiles. The results indicate that the H3K4me3 signal and chromatin accessibility at the FOXJ2 promoter are enhanced in an in vitro monocyte model by stimulation with ß2GPI/anti-ß2GPI, which mimics APS, and decreases after OICR-9429 administration. Furthermore, FOXJ2 is highly expressed in patients with primary APS (PAPS) and is the highest in patients with triple-positive antiphospholipid antibodies (aPLs). Mechanistically, FOXJ2 directly binds to the SLAMF8 promoter and activates SLAMF8 transcription. SLAMF8 further interacts with TREM1 to stimulate TLR4/NF-κB signaling and prohibit autophagy. Knockdown of FOXJ2, SLAMF8, or TREM1 blocks TLR4/NF-κB and provokes autophagy, subsequently inhibiting the release of inflammatory and thrombotic indicators. A mouse model of vascular APS is established via ß2GPI intraperitoneal injection, and the results suggest that OICR-9429 administration attenuates the inflammatory response and thrombus formation by inactivating FOXJ2/SLAMF8/TREM1 signaling. These findings highlight the overexpression of H3K4me3-mediated FOXJ2 in APS, which consequently accelerates APS pathogenesis by triggering inflammation and thrombosis via boosting the SLAMF8/TREM1 axis. Therefore, OICR-9429 is a promising candidate drug for APS therapy.

Amlodipine inhibits Synaptotagmin-4's oncogenic activity on gastric cancer proliferation by targeting calcium signaling.

BACKGROUND: Gastric cancer (GC) remains a leading cause of cancer mortality globally. Synaptotagmin-4 (SYT4), a calcium-sensing synaptic vesicle protein, has been implicated in the oncogenesis of diverse malignancies. PURPOSE: This study delineates the role of SYT4 in modulating clinical outcomes and biological behaviors in GC. METHODS: We evaluated SYT4 expression in GC specimens using bioinformatics analyses and immunohistochemistry. Functional assays included CCK8 proliferation tests, apoptosis assays via flow cytometry, confocal calcium imaging, and xenograft models. Western blotting elucidated MAPK pathway involvement. Additionally, we investigated the impact of the calcium channel blocker amlodipine on cellular dynamics and MAPK pathway activity. RESULTS: SYT4 was higher in GC tissues, and the elevated SYT4 was significantly correlated with adverse prognosis. Both univariate and multivariate analyses confirmed SYT4 as an independent prognostic indicator for GC. Functionally, SYT4 promoted tumorigenesis by fostering cellular proliferation, inhibiting apoptosis, and enhancing intracellular Ca2+ influx, predominantly via MAPK pathway activation. Amlodipine pre-treatment attenuated SYT4-driven cell growth and potentiated apoptosis, corroborated by in vivo xenograft assessments. These effects were attributed to MAPK pathway suppression by amlodipine. CONCLUSION: SYT4 emerges as a potential prognostic biomarker and a pro-oncogenic mediator in GC through a Ca2+-dependent MAPK mechanism. Amlodipine demonstrates significant antitumor effects against SYT4-driven GC, positing its therapeutic promise. This study underscores the imperative of targeting calcium signaling in GC treatment strategies.

Wuhu decoction combined with azithromycin for treatment of Mycoplasma pneumoniae pneumonia in Asian children: a systematic review and meta analysis of randomized controlled trials.

Objective: This study constitutes a pioneering systematic review and meta analysis delving into the clinical efficacy and safety of the combined therapy involving Wuhu Decoction and azithromycin for treating Mycoplasma pneumoniae pneumonia in pediatric patients. Methods: This study conducted a comprehensive computerized search, covering 6 Chinese databases and 6 English databases, to collect randomized controlled trials related to the combined use of Wuhu Decoction and azithromycin for treating Mycoplasma pneumoniae pneumonia in pediatric patients. The search was extended until August 2023. Two independent researchers were involved in literature screening, data extraction, and bias risk assessment. Meta-analysis was performed using Stata 14.0 and RevMan 5.4 software. Additionally, meta-regression analysis and subgroup analysis were carried out on primary outcomes to identify potential sources of heterogeneity and confounding factors. Results: A total of 22 randomized controlled trials involving 2,026 patients were included in this study. The combined therapy of Wuhu Decoction and azithromycin demonstrated superior efficacy compared to azithromycin alone (RR = 1.17, 95% CI [1.13, 1.21], p < 0.00001; low certainty of evidence). Additionally, patients receiving the combination therapy experienced significantly reduced the disappearance time of fever (MD = -1.42, 95% CI [-1.84, -1.00], p < 0.00001; very low certainty of evidence), disappearance time of cough (MD = -2.08, 95% CI [-2.44, -1.71], p < 0.00001; very low certainty of evidence), disappearance of pulmonary rales (MD = -1.97, 95% CI [-2.31, -1.63], p < 0.00001; very low certainty of evidence), and disappearance time of wheezing (MD = -1.47, 95% CI [-1.72, -1.22], p < 0.00001; very low certainty of evidence). Meta-regression analysis suggested that course of disease, sample size, and age might be sources of heterogeneity. Subgroup and sensitivity analyses reaffirmed the stability of these results. Furthermore, analyses of secondary outcomes such as T lymphocytes, serum inflammatory factors, and the incidence rate of adverse reactions consistently favored the combination therapy of WHD and azithromycin over azithromycin alone, with statistically significant differences. Conclusion: Based on our meta-analysis findings, the combined therapy of Wuhu Decoction and azithromycin for treating pediatric Mycoplasma pneumoniae pneumonia exhibited superior overall efficacy in comparison to azithromycin monotherapy. However, in the included 22 studies, the majority of evaluated factors showed unclear bias risks, and a persistent bias risk was consistently present within one category. Moreover, due to the low quality of evidence, interpreting these results should be approached with caution. Hence, we emphasize the necessity for future high-quality, multicenter, and large-sample clinical randomized controlled trials. These trials are essential to provide more robust data for evidence-based research and to establish higher-quality evidence support. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023465606.

Risk assessment of imported malaria in China: a machine learning perspective.

BACKGROUND: Following China's official designation as malaria-free country by WHO, the imported malaria has emerged as a significant determinant impacting the malaria reestablishment within China. The objective of this study is to explore the application prospects of machine learning algorithms in imported malaria risk assessment of China. METHODS: The data of imported malaria cases in China from 2011 to 2019 was provided by China CDC; historical epidemic data of malaria endemic country was obtained from World Malaria Report, and the other data used in this study are open access data. All the data processing and model construction based on R, and map visualization used ArcGIS software. RESULTS: A total of 27,088 malaria cases imported into China from 85 countries between 2011 and 2019. After data preprocessing and classification, clean dataset has 765 rows (85 * 9) and 11 cols. Six machine learning models was constructed based on the training set, and Random Forest model demonstrated the best performance in model evaluation. According to RF, the highest feature importance were the number of malaria deaths and Indigenous malaria cases. The RF model demonstrated high accuracy in forecasting risk for the year 2019, achieving commendable accuracy rate of 95.3%. This result aligns well with the observed outcomes, indicating the model's reliability in predicting risk levels. CONCLUSIONS: Machine learning algorithms have reliable application prospects in risk assessment of imported malaria in China. This study provides a new methodological reference for the risk assessment and control strategies adjusting of imported malaria in China.

High-throughput sequencing reveals differences in microbial community structure and diversity in the conjunctival tissue of healthy and type 2 diabetic mice.

BACKGROUND: To investigate the differences in bacterial and fungal community structure and diversity in conjunctival tissue of healthy and diabetic mice. METHODS: RNA-seq assays and high-throughput sequencing of bacterial 16 S rDNA and fungal internal transcribed spacer (ITS) gene sequences were used to identify differentially expressed host genes and fungal composition profiles in conjunctival tissues of diabetic BKS-db/db mice and BKS (control) mice. Functional enrichment analysis of differentially expressed genes and the correlation between the relative abundance of bacterial and fungal taxa in the intestinal mucosa were also performed. RESULTS: Totally, 449 differential up-regulated genes and 1,006 down-regulated genes were identified in the conjunctival tissues of diabetic mice. The differentially expressed genes were mainly enriched in metabolism-related functions and pathways. A decrease in conjunctival bacterial species diversity and abundance in diabetic mice compared to control mice. In contrast, fungal species richness and diversity were not affected by diabetes. The microbial colonies were mainly associated with cellular process pathways regulating carbohydrate and lipid metabolism, as well as cell growth and death. Additionally, some interactions between bacteria and fungi at different taxonomic levels were also observed. CONCLUSION: The present study revealed significant differences in the abundance and composition of bacterial and fungal communities in the conjunctival tissue of diabetic mice compared to control mice. The study also highlighted interactions between bacteria and fungi at different taxonomic levels. These findings may have implications for the diagnosis and treatment of diabetes.

Simultaneous photocatalytic degradation and SERS detection of tetracycline with self-sustainable and recyclable ternary PI/TiO2/Ag flexible microfibers.

Facile and efficient photocatalysts using sunlight, as well as fast and sensitive surface-enhanced Raman spectroscopy (SERS) substrates, are urgently needed for practical degradation of tetracycline (TC). To meet these requirements, a new paradigm for PI/TiO2/Ag organic‒inorganic ternary flexible microfibers based on semiconducting titanium dioxide (TiO2), the noble metal silver (Ag) and the conjugated polymer polyimide (PI) was developed by engineering a simple method. Under sunlight, the photocatalytic characteristics of the PI/TiO2/Ag flexible microfibers containing varying amounts of Ag quantum dots (QDs) were evaluated with photocatalytic degradation of TC in aqueous solution. The results demonstrated that the amount of Ag affected the photocatalytic activity. Among the tested samples, PI/TiO2/Ag-0.07 (93.1%) exhibited a higher photocatalytic degradation rate than PI/TiO2 (25.7%), PI/TiO2/Ag-0.05 (77.7%), and PI/TiO2/Ag-0.09 (63.3%). This observation and evaluation conducted in the present work strongly indicated a charge transfer mechanism. Moreover, the PI/TiO2/Ag-0.07 flexible microfibers exhibited highly sensitive SERS detection, as demonstrated by the observation of the Raman peaks for TC even at an extremely low concentration of 10-10 moles per liter. The excellent photocatalytic performance and SERS detection capability of the PI/TiO2/Ag flexible microfibers arose from the Schottky barrier formed between Ag and TiO2 and also from the outstanding plasmonic resonance and visible light absorptivity of Ag, along with immobilization by the PI. The successful synthesis of PI/TiO2/Ag flexible microfibers holds significant promise for sensitive detection and efficient photocatalytic degradation of antibiotics.

Analysis of microstate features for Parkinson's disease based on reliability validation.

BACKGROUND: Parkinson's disease (PD) is a disorder with abnormal changes in brain activity. The lack of objective indicators makes the assessment of PD progression difficult. Assessment of brain activity changes in PD may offer a potential solution. NEW METHOD: Electroencephalogram (EEG) microstates reflect global dynamic changes in the brain. Therefore, we utilized microstates to assess changes in PD brain activity. However, the effect of epoch duration on the reliability of microstate analyses in PD is unclear. Thus, we first assessed the effect of data duration on the reliability of microstate topography and temporal features in PD and older healthy individuals. According to the reliability assessment, EEG epochs with high reliability were selected for microstate analysis in PD. Finally, we investigated the correlation between microstate features and clinical scales to determine whether these features could serve as objective indicators to evaluate PD progression. RESULTS: Microstate analysis features that show high reliability for 3 min and above epoch durations. The topology of microstate D was significantly changed in PD compared to healthy controls, as well as the temporal features of microstates C and D. Additionally, the occurrence of C was negatively correlated with MoCA, and the duration of D was positively correlated with UPDRS. COMPARISON WITH EXISTING METHOD(S): High reliability of PD microstate features obtained by our approach. CONCLUSION: EEG for PD microstate analysis should be at least 3 min. Microstate analysis is expected to provide new ideas and objective indicators for assessing Parkinson's disease progression in the clinical setting.

A Combined Method of Seismic Monitoring and Transient Electromagnetic Detection for the Evaluation of Hydraulic Fracturing Effect in Coal Burst Prevention.

In order to mitigate the risk of roof-dominated coal burst in underground coal mining, horizontal long borehole staged hydraulic fracturing technology has been prevailingly employed to facilitate the weakening treatment of the hard roof in advance. Such weakening effect, however, can hardly be evaluated, which leads to a lack of a basis in which to design the schemes and parameters of hydraulic fracturing. In this study, a combined underground-ground integrated microseismic monitoring and transient electromagnetic detection method was utilized to carry out simultaneous evaluations of the seismic responses to each staged fracturing and the apparent resistivity changes before and after all finished fracturing. On this basis, the comparable and applicable fracturing effects on coal burst prevention were evaluated and validated by the distribution of microseismic events and their energy magnitude during the mining process. Results show that the observed mining-induced seismic events are consistent with the evaluation results obtained from the combined seismic-electromagnetic detection method. However, there is a limited reduction effect on resistivity near the fractured section that induces far-field seismic events. Mining-induced seismic events are concentrated primarily within specific areas, while microseismic events in the fractured area exhibit high frequency but low energy overall. This study validates the rationality of combined seismic-electromagnetic detection results and provides valuable insights for optimizing fracturing construction schemes as well as comprehensively evaluating outcomes associated with underground directional long borehole staged hydraulic fracturing.

Effects of an inoculation dose of Issatchenkia terricola WJL-G4 on physicochemical properties, active substances, and antioxidant capacity of black, red, and white currant juice.

BACKGROUND: Due to the high level of organic acids - primarily citric acid - black, red, and white currants have an excessively sour taste, making taste adjustment during processing challenging. This study investigated and evaluated the effects of an inoculation dose of the acid-reducing yeast Issatchenkia terricola WJL-G4 on several aspect such as physicochemical properties, chromaticity, active substances, and antioxidant capacity. A sensory evaluation was also conducted. RESULTS: The results indicated that, when the inoculation dose increased from 2% to 12%, the total phenol, total flavonoid, and total anthocyanin content, and antioxidant capacity in currant juice decreased. A low inoculation dose (2-4%) was beneficial for preserving the total phenol and total flavonoid content. Although the levels of most phenolic compounds decreased, the concentrations of caffeic acid, p-coumaric acid, ferulic acid, rutin, and epicatechin were significantly higher than the control after fermentation. Overall acceptability and taste scores of fermented currants improved compared with those of the control group. CONCLUSION: This experiment provided an effective solution, with a theoretical basis, to the problems of the sour taste and harsh flavor of currant juice. © 2024 Society of Chemical Industry.

Enhanced antibacterial activity of bovine milk exosome-based drug formulation against bacterial pathogens.

Milk is not only a source of nutrients, but also contains exosomes (Exo) that can serve as a vehicle for drug delivery. Here, we obtained bovine milk Exo using three efficient methods, demonstrating high quality for commercial production. The optimized Exo displayed a size of 105.2 nm and an entrapment efficiency of 88.4 %. The Exo has been functionalized with a combination therapy comprising isobavachalcone (IS) and polymyxin B (PB), referred to as IP-Exo. The antibacterial efficacy of IP-Exo was significantly enhanced, enabling the elimination of 99 % of multidrug-resistant (MDR) bacterial pathogens in 4 h. Furthermore, scanning electron microscopy images demonstrated that the drug combination led to the complete dismantling of the bacterial structure. IP-Exo showed nearly 100 % microbial inhibition in fresh orange juice and accelerated wound healing in mouse models. Collectively, IP-Exo provides excellent potential for application within the food industry and animal husbandry as a defense against bacterial pathogens.

Overcoming Thermal Quenching in X-ray Scintillators through Multi-Excited State Switching.

X-ray scintillators have gained significant attention in medical diagnostics and industrial applications. Despite their widespread utility, scintillator development faces a significant hurdle when exposed to elevated temperatures, as it usually results in reduced scintillation efficiency and diminished luminescence output. Here we report a molecular design strategy based on a hybrid perovskite (TpyBiCl5) that overcomes thermal quenching through multi-excited state switching. The structure of perovskite provides a platform to modulate the luminescence centers. The rigid framework constructed by this perovskite structure stabilized its triplet states, resulting in TpyBiCl5 exhibiting an approximately 12 times higher (45 % vs. 3.8 %) photoluminescence quantum yield of room temperature phosphorescence than that of its organic ligand (Tpy). Most importantly, the interactions between the components of this perovskite enable the mixing of different excited states, which has been revealed by experimental and theoretical investigations. The TpyBiCl5 scintillator exhibits a detection limit of 38.92 nGy s-1 at 213 K and a detection limit of 196.31 nGy s-1 at 353 K through scintillation mode switching between thermally activated delayed fluorescence and phosphorescence. This work opens up the possibility of solving the thermal quenching in X-ray scintillators by tuning different excited states.

Recent progress in nanomaterials for bacteria-related tumor therapy.

Many studies suggest that tumor microbiome closely relates to the oncogenesis and anti-tumor responses in multiple cancer types (e.g., colorectal cancer (CRC), breast cancer, lung cancer and pancreatic cancer), thereby raising an emerging research area of bacteria-related tumor therapy. Nanomaterials have long been used for both cancer and bacterial infection treatment, holding great potential for bacteria-related tumor therapy. In this review, we summarized recent progress in nanomaterials for bacteria-related tumor therapy. We focus on the types and mechanisms of pathogenic bacteria in the development and promotion of cancers and emphasize how nanomaterials work. We also briefly discuss the design principles and challenges of nanomaterials for bacteria-related tumor therapy. We hope this review can provide some insights into this emerging and rapidly growing research area.

Ascertaining sensitive exposure biomarkers of various metal(loid)s to embryo implantation.

Close relationships exist between metal(loid)s exposure and embryo implantation failure (EIF) from animal and epidemiological studies. However, there are still inconsistent results and lacking of sensitive metal(loid) exposure biomarkers associated with EIF risk. We aimed to ascertain sensitive metal(loid) biomarkers to EIF and provide potential biological explanations. Candidate metal(loid) biomarkers were measured in the female hair (FH), female serum (FS), and follicular fluid (FF) with various exposure time periods. An analytical framework was established by integrating epidemiological association results, comprehensive literature searching, and knowledge-based adverse outcome pathway (AOP) networks. The sensitive biomarkers of metal(loid)s along with potential biological pathways to EIF were identified in this framework. Among the concerned 272 candidates, 45 metal(loid)s biomarkers across six time periods and three biomatrix were initially identified by single-metal(loid) analyses. Two biomarkers with counterfactual results according to literature summary results were excluded, and a total of five biomarkers were further determined from 43 remained candidates in mixture models. Finally, four sensitive metal(loid) biomarkers were eventually assessed by overlapping AOP networks information, including Se and Co in FH, and Fe and Zn in FS. AOP networks also identified key GO pathways and proteins involved in regulation of oxygen species biosynthetic, cell proliferation, and inflammatory response. Partial dependence results revealed Fe in FS and Co in FH at their low levels might be potential sensitive exposure levels for EIF. Our study provided a typical framework to screen the crucial metal(loid) biomarkers and ascertain that Se and Co in FH, and Fe and Zn in FS played an important role in embryo implantation.