Hydrogen sulfide attenuates chilling injury in loquat fruit by alleviating oxidative stress and maintaining cell membrane integrity.

The effects of hydrogen sulfide (H2S) on chilling injury (CI), reactive oxygen species (ROS) metabolism, sugar metabolism, pentose phosphate pathway (PPP), and membrane lipid metabolism in loquat fruit throughout the refrigerated period were investigated in this study. The findings indicated that H2S application restrained the increase in internal browning (IB), malondialdehyde (MDA) content, and electrolyte leakage, while sustaining higher total phenolic and total flavonoid levels, and lower soluble quinone content in loquat fruit. Besides, H2S promoted antioxidant accumulation and increased antioxidant enzyme activities by the regulation of ROS metabolism, along with increasing fructose and glucose levels and reducing power by activating sugar metabolism and PPP. Furthermore, H2S treatment retarded the degradation of phospholipids and fatty acids in loquat fruit by modulating membrane lipid metabolism relevant enzyme activities. These findings indicated that H2S application mitigated CI in loquat fruit by alleviating oxidative stress and maintaining cell membrane structural integrity.

Comparative study on the antioxidant efficacy of Adinandra nitida extracts in inhibiting lipid oxidation in edible oils.

Exploring natural antioxidants is essential to delay lipid oxidation. This study investigated the inhibitory effect of Adinandra nitida (AN) extract in six edible oils, compared to TP and TBHQ. Methods included extract preparation, bioactive compounds analysis, in vitro antioxidant activities by FRAP, DPPH, and ABTS assays, fatty acid composition detection, and POV determination. The results showed that AN was rich in total flavonoids, total phenols and had better iron ion reduction ability than TBHQ. In oleic and linoleic acid-rich oils, AN significantly delayed early-stage lipid oxidation, outperforming TP and TBHQ. In linolenic acid-rich oils, AN maintained a stable effect. Molecular docking studies revealed strong binding interactions between main compounds and fatty acids, with Camelliaside A in (7.83) showing higher binding energy to linolenic acid than TBHQ (7.64), supporting the antioxidant effects. These findings suggest AN as a promising natural alternative to synthetic antioxidants, enhancing oil stability and shelf life.

A new perspective on antiangiogenic antibody drug resistance: Biomarkers, mechanisms, and strategies in malignancies.

Drug resistance of malignant tumor leads to disease progression be the bottleneck in clinical treatment. Antiangiogenic therapy, which aims to "starve" the tumor by inhibiting angiogenesis, is one of the key strategies in clinical oncology treatments. Recently, dozens of investigational antibody drugs and biosimilars targeting angiogenesis have obtained regulatory approval for the treatment of various malignancies. Moreover, a new generation of bispecific antibodies based on the principle of antiangiogenesis are being advanced for clinical trial to overcome antiangiogenic resistance in tumor treatment or enhance the efficacy of monotherapy. Tumors often develop resistance to antiangiogenesis therapy, presenting as refractory and sometimes even resistant to new therapies, for which there are currently no effective management strategies. Thus, a detailed understanding of the mechanisms mediating resistance to antiangiogenesis antibodies is crucial for improving drug effectiveness and achieving a durable response to antiangiogenic therapy. In this review, we provide a novel perspective on the tumor microenvironment, including antibody structure, tumor stroma, and changes within tumor cells, to analyze the multifactorial reasons underlying resistance to antiangiogenesis antibodies. The review also enumerates biomarkers that indicate resistance and potential strategies for monitoring resistance. Furthermore, based on recent clinical and preclinical studies, we summarize potential strategies and translational clinical trials aimed at overcoming resistance to antiangiogenesis antibodies. This review provides a valuable reference for researchers and clinical practitioners involved in the development of new drugs or therapeutic strategies to overcome antiangiogenesis antibodies resistance.

Comprehensive analysis of the relationship between yield stress and dewatering performance in sludge conditioning: Insights from various treatment methods.

Understanding the relationship between sludge yield stress (σy) and dewatering performance is essential for optimizing sludge conditioning processes. This study systematically investigates the effects of various conditioning methods-including thermal hydrolysis (TH), freezing/thawing (FT), anaerobic digestion (AD), polyaluminum chloride (PAC), polyacrylamide (PAM), and Fenton treatment (Fenton)-on sludge yield stress and its correlation with dewatering efficiency. Using linear regression, partial least squares regression (PLSR), and correlation heatmap analyses, we reveal significant variations in the correlation between σy and dewatering indexes, including moisture content (Mc), capillary suction time (CST), and bound water proportion (Wb/Wt), depending on the conditioning method and intensity. Under FT and PAM conditioning, σy shows a strong negative linear correlation with dewatering performance, with Pearson's r values exceeding -0.880, indicating that a decrease in σy corresponds to improved dewatering efficiency. Conversely, AD conditioning exhibits a positive linear correlation, with r values up to 0.993, suggesting that an increase in σy correlates with reduced dewatering efficiency. For TH, PAC, and Fenton treatments, the correlation between σy and dewatering metrics is highly sensitive to changes in treatment intensity. In the PLSR analysis, the VIP values, which quantify the importance of each predictor variable, indicate that Wb/Wt in TH conditioning (VIP = 1.649) and CST in PAC (VIP = 1.309) and Fenton (VIP = 1.299) conditioning strongly influence σy. This study highlights the significant impact of conditioning methods and intensities on the correlation between σy and dewatering performance. While σy provides valuable insights as a predictive indicator, its predictive power is limited in more complex conditioning scenarios. Therefore, optimizing conditioning intensity and incorporating multiple rheological parameters are essential for achieving superior sludge dewatering outcomes.

Integrated GMPS and RAMP3 as a signature to predict prognosis and immune heterogeneity in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a highly fatal malignant worldwide. As different expression levels of specific genes can lead to different HCC outcomes, we aimed to develop a gene signature capable of predicting HCC prognosis. METHODS: In this study, transcriptomic sequencing and relevant clinical data were extracted from public platforms. The guanine monophosphate synthase (GMPS)|receptor activity-modifying protein 3 (RAMP3) gene pair was developed based on the relative values of gene expression levels. Nomograms were developed using R software. Immune status was assessed through single-sample gene set enrichment analysis. GMPS knockdown was achieved through siRNA transfection. Quantitative reverse transcription PCR, apoptosis assays, and cell proliferation were performed to verify the function of GMPS|RAMP3 in HCC cells. RESULTS: Here, a gene pair containing GMPS and RAMP3 was successfully constructed. We demonstrated that the GMPS|RAMP3 gene pair was an independent predictor with strong prognostic prediction power, based on which a nomogram was established. Functional analysis revealed that the enrichment of cell cycle-related pathways and immune status differed considerably between the two groups, with cell cycle-related genes highly expressed in the high GMPS|RAMP3 value group. Finally, cell experiments indicated that GMPS knockdown significantly repressed proliferation, promoted apoptosis, and enhanced the sensitivity of HCC cells to gemcitabine. CONCLUSIONS: The gene pair GMPS|RAMP3 is a novel prognostic predictor of HCC, providing a promising approach to the treatment and assessment of immune heterogeneity in HCC.

Segmentation of Heart Sound Signal Based on Multi-Scale Feature Fusion and Multi-Classification of Congenital Heart Disease.

Analyzing heart sound signals presents a novel approach for early diagnosis of pediatric congenital heart disease. The existing segmentation algorithms have limitations in accurately distinguishing the first (S1) and second (S2) heart sounds, limiting the diagnostic utility of cardiac cycle data for pediatric pathology assessment. This study proposes a time bidirectional long short-term memory network (TBLSTM) based on multi-scale analysis to segment pediatric heart sound signals according to different cardiac cycles. Mel frequency cepstral coefficients and dynamic characteristics of the heart sound fragments were extracted and input into random forest for multi-classification of congenital heart disease. The segmentation model achieved an overall F1 score of 94.15% on the verification set, with specific F1 scores of 90.25% for S1 and 86.04% for S2. In a situation where the number of cardiac cycles in the heart sound fragments was set to six, the results for multi-classification achieved stabilization. The performance metrics for this configuration were as follows: accuracy of 94.43%, sensitivity of 95.58%, and an F1 score of 94.51%. Furthermore, the segmentation model demonstrates robustness in accurately segmenting pediatric heart sound signals across different heart rates and in the presence of noise. Notably, the number of cardiac cycles in heart sound fragments directly impacts the multi-classification of these heart sound signals.

Low temperature carbonization and synergistic flame retardancy of cotton fabric coated by phosphorus­nitrogen flame retardants.

To solve the problems of flammability and smoldering of cotton fabric, its flame-retardant finishing was executed with biomass wool keratin (WK) and cyclic phosphate ester (CPE) through the soaking and baking process. The synergistic mechanism of WK low-temperature melting and CPE catalytic dehydration prompted the formation of protective carbonization layer on cotton fabric surface, and this protective layer reduced its pyrolysis rate, inhibited the production of combustible materials and improved its flame retardancy. The results of synchronous thermal analysis indicate that the initial decomposition temperature of WK and CPE is lower than that of cotton fabric, and they precede the endothermic degradation before fabric main body. This effectively promotes the low-temperature carbonization of cotton fabric and inhibits its pyrolysis. The initial decomposition temperature of WK/CPE treated fabrics advances by 47.9 °C-97.8 °C, presenting significant low-temperature carbonization trend. Moreover, they form 3.0 %-20.0 % aromatic structural char before the pyrolysis of cotton cellulose due to the low-temperature dehydration and carbonization reactions. The damage length after vertical burning is only 4.0 cm for treated fabric with five layers, its after-flame and smoldering disappear, and its limiting oxygen index value increases to 28.7 %. This research provides an effective idea for the flammability and smoldering problems of cotton fabric.

Spatial variation, emissions, transport, and risk assessment of organophosphate esters in two large petrochemical complexes in southern China.

Organophosphate esters (OPEs) serve as significant flame retardants and plasticizers in various petrochemical downstream products. The petrochemical industry could be a potential source of atmospheric OPEs, but their emissions from this industry are poorly understood. The present study revealed the spatial variation, emission, and atmospheric transport of traditional and novel OPEs (TOPEs and NOPEs, respectively) in atmospheric particulate matter (PM) across Hainan and Guangdong petrochemical complexes (HNPC and GDPC, respectively) in southern China. The total concentrations of TOPEs ranged from 232 to 46,002 pg/m3 and from 200 to 20,347 pg/m3 in the HNPC and GDPC, respectively, which were substantially higher than those of NOPEs (HNPC: 23.5-147 pg/m3, GDPC: 13.9-465 pg/m3). Enterprises involved in the production of downstream petrochemical products presented relatively high concentrations of OPEs, indicating evident emissions of these pollutants in the petrochemical industry. The correlations of PM-bound OPEs in the atmosphere are determined mainly by their coaddition to industrial products or their coexistence in technical mixtures. The annual emissions of TOPEs and NOPEs in the HNPC were 42.6 kg and 0.34 kg, respectively, and those in the GDPC were 116 kg and 1.85 kg, respectively. OPEs from the HNPC can reach Vietnam, Cambodia, and Guangxi Province, China, and those from the GDPC can reach Guangxi Province and Hunan Province via atmospheric transmission after 24 h of emission. The OPE concentrations reaching the receptor regions were generally less than 3.20 pg/m3. Risk assessment revealed that OPE inhalation exposure on two petrochemical complexes likely poses minor risks for people living in the study areas, but the risk resulting from two chlorinated OPEs should be noted since they are close to the threshold values. This study has implications for enhancing control measures for OPE emissions to reduce health risks related to the petrochemical industry.

Vascular access type and prognosis in elderly hemodialysis patients: a propensity-score-matched study.

BACKGROUND: To compare the impact of tunneled cuffed catheters (TCCs) and arteriovenous fistulas (AVFs) on outcomes in elderly hemodialysis (HD) patients. METHODS: A retrospective matched cohort study was performed. Propensity score matching (PSM) was applied to balance the baseline conditions, and we compared all-cause mortality, major adverse cardiovascular and cerebrovascular events (MACCEs), hospitalization, and infection rates between AVF and TCC patients ≥70 years old. Cox survival analysis was used to analyze the risk factors for death. RESULTS: There were 2119 patients from our center in the Chinese National Renal Data System (CNRDS) between 1 January 2010 and 10 October 2023. Among these patients, 77 TCC patients were matched with 77 AVF patients. There was no significant difference in all-cause mortality between the TCC and AVF groups (30.1/100 vs. 33.3/100 patient-years, p = 0.124). Among the propensity score-matched cohorts, no significant differences in Kaplan-Meier curves were observed between the two groups (log-rank p = 0.242). The TCC group had higher rates of MACCEs, hospitalization, and infection than the AVF group (33.7/100 vs. 29.5/100 patient-years, 101.2/100 vs. 79.5/100 patient-years, and 30.1/100 vs. 14.1/100 patient-years, respectively). Multivariate analysis showed that high Charlson comorbidity index (CCI) score was a risk factor for death. CONCLUSIONS: There was no significant difference in all-cause mortality between elderly HD patients receiving TCCs and AVFs. Compared with those with a TCC, elderly HD patients with an AVF have a lower risk of MACCEs, hospitalization, and infection.

A novel scoring system based on sIL-2R for predicting IVIG resistance in Chinese children with KD.

OBJECTIVE: This study aimed to develop a novel scoring system utilizing circulating interleukin (IL) levels to predict resistance to intravenous immunoglobulin (IVIG) in Chinese patients with Kawasaki disease (KD). We further compared this scoring system against six previously established scoring methods to evaluate its predictive performance. METHODS: A retrospective analysis was conducted on KD patients who were treated at the cardiovascular medical ward of our institution from January 2020 to December 2022. Six scoring systems (Egami, Formosa, Harada, Kobayashi, Lan and Yang) were analyzed, and a new scoring system was developed based on our data. RESULTS: In our study, 521 KD patients were recruited, 42 of whom (8.06%) were identified as resistant to IVIG. Our study indicated that IVIG-resistant KD patients were at an increased risk for the development of coronary arterial lesions (CALs) (P = 0.001). The evaluation of IVIG resistance using various scoring systems revealed differing levels of sensitivity and specificity, as follows: Egami (38.10% and 88.52%), Formosa (95.24% and 41.13%), Harada (78.57% and 43.22%), Kobayashi (66.67% and 74.95%), Lan (66.67% and 73.49%), and Yang (69.05% and 77.24%). Our novel scoring system utilizing sIL-2R demonstrated the highest sensitivity and specificity of 69.29% and 83.91%, respectively, and calibration curves indicated a favorable predictive accuracy of the model. CONCLUSION: Our newly developed scoring system utilizing sIL-2R demonstrated superior predictive performance in identifying IVIG resistance among Chinese patients with KD.

Characterization of a novel phage against multidrug-resistant Klebsiella pneumoniae.

Multidrug-resistant Klebsiella pneumoniae (MDR-KP) poses a significant challenge in global healthcare, underscoring the urgency for innovative therapeutic approaches. Phage therapy emerges as a promising strategy amidst rising antibiotic resistance, emphasizing the crucial need to identify and characterize effective phage resources for clinical use. In this study, we introduce a novel lytic phage, RCIP0100, distinguished by its classification into the Chaoyangvirus genus and Fjlabviridae family based on International Committee on Taxonomy of Viruses (ICTV) criteria due to low genetic similarity to known phage families. Our findings demonstrate that RCIP0100 exhibits broad lytic activity against 15 out of 27 tested MDR-KP strains, including diverse profiles such as carbapenem-resistant K. pneumoniae (CR-KP). This positions phage RCIP0100 as a promising candidate for phage therapy. Strains resistant to RCIP0100 also showed increased susceptibility to various antibiotics, implying the potential for synergistic use of RCIP0100 and antibiotics as a strategic countermeasure against MDR-KP.

Association between composite dietary antioxidant and bone mineral density in children and adolescents aged 8-19 years: findings from NHANES.

Dietary antioxidants may have beneficial effects on bone health, but it remains uncertain in children and adolescents. This study investigates the association of composite dietary antioxidant index (CDAI) with bone mineral density (BMD) in children and adolescents aged 8-19 years from the National Health and Nutrition Examination Survey (NHANES) 2007-2010. The study assessed the relationship between CDAI and BMD in 2994 individuals aged 8-19 years (average age 13.48 ± 3.32 years) from the NHANES 2007-2010. Multivariate linear regression analyses were utilized to detect the association between CDAI and total spine, femur neck, and total femur BMD, adjusting for confounders including age, race/ethnicity, sex, poverty income ratio (PIR), body mass index (BMI), serum phosphorus and calcium. Stratified analyses and interaction tests were performed to examine the stability of the results. The weighted characteristics showed that subjects in the fourth CDAI quartile were more likely to be older, men, and Non-Hispanic White. They have higher values of serum total calcium and phosphorus. After adjusting all confounders, CDAI was positively associated with the total spine (ß = 0.0031 95% CI 0.0021-0.0040), total femur (ß = 0.0039 95% CI 0.0028-0.0049), and femur neck BMD (ß = 0.0031 95% CI 0.0021-0.0040) in children and adolescents. Furthermore, we found no interaction effects between different race/ethnicity, age, and sex groups. Our findings suggest that dietary intake of multiple antioxidants was positively associated with BMD in children and adolescents. These findings provide valuable evidence for improving bone health in the early stages of life. However, more prospective studies are required to validate our findings and their causal relationship.

Association of lower urinary tract symptoms and geriatric nutritional risk index in men: a cross-sectional study based on NHANES.

Background: Despite previous literature exploring the factors influencing lower urinary tract symptoms (LUTS), few studies have examined the relationship between nutritional status and LUTS. Objectives: The objective of this research was to evaluate the relationship between LUTS and Geriatric Nutritional Risk Index (GNRI) in middle-aged and older men. Methods: We included 2,607 men in the NHANES 2005-2006 and 2007-2008 cycles for cross-sectional analysis. We screened for LUTS based on four specific questions on the relevant questionnaire. We calculated GNRI according to the relevant calculation formula and included other covariates. Multivariate logistic analysis using GNRI as the principal independent variable and adjusting for other covariates were used to determine the association with LUTS, nocturia, and daytime LUTS. Results: According to the responses to the questionnaire, out of 2,607 eligible participants, 471 had LUTS, 906 had nocturia, and 819 had daytime LUTS. In the unadjusted regression model, LUTS (OR = 0.93, 95% CI = 0.91-0.96, p < 0.001), nocturia (OR = 0.90, 95% CI = 0.88-0.93, p < 0.001), and daytime LUTS (OR = 0.96, 95% CI = 0.94-0.99, p = 0.002) were significantly negatively associated with GNRI. After adjustment by adding covariates, LUTS (OR = 0.97,95% CI =0.94-0.99, p = 0.026) and nocturia (OR = 0.94, 95% CI =0.91-0.93, p < 0.001) were significantly negatively associated with GNRI. Conclusion: Low GNRI was associated with the development of LUTS. In the prevention and treatment of LUTS, urologists should consider the impact of nutritional status on LUTS, and interventions for nutritional status may prevent and improve LUTS.

The significance of lipid metabolism reprogramming of tumor-associated macrophages in hepatocellular carcinoma.

In the intricate landscape of the tumor microenvironment, tumor-associated macrophages (TAMs) emerge as a ubiquitous cellular component that profoundly affects the oncogenic process. The microenvironment of hepatocellular carcinoma (HCC) is characterized by a pronounced infiltration of TAMs, underscoring their pivotal role in modulating the trajectory of the disease. Amidst the evolving therapeutic paradigms for HCC, the strategic reprogramming of metabolic pathways presents a promising avenue for intervention, garnering escalating interest within the scientific community. Previous investigations have predominantly focused on elucidating the mechanisms of metabolic reprogramming in cancer cells without paying sufficient attention to understanding how TAM metabolic reprogramming, particularly lipid metabolism, affects the progression of HCC. In this review article, we intend to elucidate how TAMs exert their regulatory effects via diverse pathways such as E2F1-E2F2-CPT2, LKB1-AMPK, and mTORC1-SREBP, and discuss correlations of TAMs with these processes and the characteristics of relevant pathways in HCC progression by consolidating various studies on TAM lipid uptake, storage, synthesis, and catabolism. It is our hope that our summary could delineate the impact of specific mechanisms underlying TAM lipid metabolic reprogramming on HCC progression and provide useful information for future research on HCC and the development of new treatment strategies.

GNPNAT1 Serves as a Prognostic Biomarker Correlated with Immune Infiltration and Promotes Cancer Cell Metastasis through Stabilization of Snai2 in Lung Adenocarcinoma.

BACKGROUND: Lung cancer is a common malignant tumor with high morbidity and mortality rate. Glucosamine 6-phosphate N-acetyltransferase (GNPNAT1), which serves as a critical enzyme in hexosamine biosynthetic pathway (HBP), has been identified as a metastasis-associated gene and is upregulated in lung adenocarcinoma (LUAD). However, the exact role and related mechanism of GNPNAT1 in LUAD metastasis remain unknown. METHODS: We analyzed the expression of GNPNAT1 in the public databases and confirmed the results by immunohistochemistry (IHC). The biological functions of GNPNAT1 in LUAD were investigated based on The Cancer Genome Atlas (TCGA). Correlations between GNPNAT1 and cancer immune characteristics were analyzed via the Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression data (ESTIMATE) and Cell-type Identification by Estimating Relative Subsets of RNA Transcript (CIBERSORT) R package. The underlying mechanisms of altered GNPNAT1 expression on LUAD cell tumorigenesis, proliferation, migration, invasion, and metastasis were explored in vitro and in vivo. RESULTS: We demonstrated that GNPNAT1 expression was significantly increased in LUAD and negatively associated with the overall survival (OS) of patients. hsa-miR-1-3p and hsa-miR-26a-5p were identified as upstream miRNA targets of GNPNAT1. GNPNAT1 was associated with the infiltration levels of CD8 T cells, memory-activated CD4 T cells, NK cells resting, macrophages M0, macrophages M1, neutrophils, gamma delta T cells, and eosinophils, while it was negatively correlated with memory-resting CD4 T cells, regulatory T cells (Tregs), resting NK cells, monocytes, resting dendritic cells, and resting mast cells. GNPNAT1 knockdown significantly inhibited proliferation, migration, invasion, epithelial-mesenchymal transition (EMT) process, and metastasis of LUAD cells, while overexpression of GNPNAT1 revealed the opposite effects. Rescue assay showed that Snai2 knockdown reversed GNPNAT1-induced LUAD cells migration, invasion, and EMT. Mechanistically, GNPNAT1 promoted cancer cell metastasis via repressing ubiquitination degradation of Snai2 in LUAD. CONCLUSIONS: Taken together, these data indicate that GNPNAT1 serves as a prognostic biomarker for LUAD patient. Additionally, GNPNAT1 is critical for promoting tumorigenesis and metastasis of LUAD cells and may be a potential therapeutic target for preventing LUAD metastasis.

Immunocyte membrane-derived biomimetic nano-drug delivery system: a pioneering platform for tumour immunotherapy.

Tumor immunotherapy characterized by its high specificity and minimal side effects has achieved revolutionary progress in the field of cancer treatment. However, the complex mechanisms of tumor immune microenvironment (TIME) and the individual variability of patients' immune system still present significant challenges to its clinical application. Immunocyte membrane-coated nanocarrier systems, as an innovative biomimetic drug delivery platform, exhibit remarkable advantages in tumor immunotherapy due to their high targeting capability, good biocompatibility and low immunogenicity. In this review we summarize the latest research advances in biomimetic delivery systems based on immune cells for tumor immunotherapy. We outline the existing methods of tumor immunotherapy including immune checkpoint therapy, adoptive cell transfer therapy and cancer vaccines etc. with a focus on the application of various immunocyte membranes in tumor immunotherapy and their prospects and challenges in drug delivery and immune modulation. We look forward to further exploring the application of biomimetic delivery systems based on immunocyte membrane-coated nanoparticles, aiming to provide a new framework for the clinical treatment of tumor immunity.

Data-Driven Engineering of Phages with Tunable Capsule Tropism for Klebsiella pneumoniae.

Klebsiella pneumoniae, a major clinical pathogen known for causing severe infections, is attracting heightened attention due to its escalating antibiotic resistance. Phages are emerging as a promising alternative to antibiotics; however, their specificity to particular hosts often restricts their use. In this study, a collection of 114 phages is obtained and subjected to analysis against 238 clinical K. pneumoniae strains, revealing a spectrum of lytic behaviors. A correlation between putative tail protein clusters and lysis patterns leads to the discovery of six receptor-binding protein (RBP) clusters that determine host capsule tropism. Significantly, RBPs with cross-capsular lysis capabilities are identified. The newly-identified RBPs provide a toolbox for customizing phages to target diverse capsular types. Building on the toolbox, the engineered phages with altered RBPs successfully shifted and broadened their host capsule tropism, setting the stage for tunable phage that offer a precise and flexible solution to combat K. pneumoniae infections.

Understanding the rapid spread of antimicrobial resistance genes mediated by IS26.

Insertion sequences (ISs) promote the transmission of antimicrobial resistance genes (ARGs) across bacterial populations. However, their contributions and dynamics during the transmission of resistance remain unclear. In this study, we selected IS26 as a representative transposable element to decipher the relationship between ISs and ARGs and to investigate their transfer features and transmission trends. We retrieved 2656  translocatable  IS 26 -bounded  units with  ARGs (tIS26-bUs-ARGs) in complete bacterial genomes from the NCBI RefSeq database. In total, 124 ARGs spanning 12 classes of antibiotics were detected, and the average contribution rate of IS26 to these genes was 41.2%. We found that  IS 26 -bounded  units (IS26-bUs) mediated extensive ARG dissemination within the bacteria of the Gammaproteobacteria class, showing strong transfer potential between strains, species, and even phyla. The IS26-bUs expanded in bacterial populations over time, and their temporal expansion trend was significantly correlated with antibiotic usage. This wide dissemination could be due to the nonspecific target site preference of IS26. Finally, we experimentally confirmed that the introduction of a single copy of IS26 could lead to the formation of a composite transposon mediating the transmission of "passenger" genes. These observations extend our knowledge of the IS26 and provide new insights into the mediating role of ISs in the dissemination of antibiotic resistance.

Mechanism of heterochromatin remodeling revealed by the DDM1 bound nucleosome structures.

The SWI/SNF2 chromatin remodeling factor decreased DNA methylation 1 (DDM1) is essential for the silencing of transposable elements (TEs) in both euchromatic and heterochromatic regions. Here, we determined the cryo-EM structures of DDM1-nucleosomeH2A and DDM1-nucleosomeH2A.W complexes at near-atomic resolution in the presence of the ATP analog ADP-BeFx. The structures show that nucleosomal DNA is unwrapped more on the surface of the histone octamer containing histone H2A than that containing histone H2A.W. DDM1 embraces one DNA gyre of the nucleosome and interacts with the N-terminal tails of histone H4. Although we did not observe DDM1-H2A.W interactions in our structures, the results of the pull-down experiments suggest a direct interaction between DDM1 and the core region of histone H2A.W. Our work provides mechanistic insights into the heterochromatin remodeling process driven by DDM1 in plants.