Re-Engineering Fungal Nonribosomal Peptide Synthetases by Module Dissection and Duplicated Thiolation Domains.

Unnatural product (uNP) nonribosomal peptides promise to be a valuable source of pharmacophores for drug discovery. However, the extremely large size and complexity of the nonribosomal peptide synthetase (NRPS) enzymes pose formidable challenges to the production of such uNPs by combinatorial biosynthesis and synthetic biology. Here we report a new NRPS dissection strategy that facilitates the engineering and heterologous production of these NRPSs. This strategy divides NRPSs into "splitting units", each forming an enzyme subunit that contains catalytically independent modules. Functional collaboration between the subunits is then facilitated by artificially duplicating, at the N-terminus of the downstream subunit, the linker - thiolation domain - linker fragment that is resident at the C-terminus of the upstream subunit. Using the suggested split site that follows a conserved motif in the linker connecting the adenylation and the thiolation domains allows cognate or chimeric splitting unit pairs to achieve productivities that match, and in many cases surpass those of hybrid chimeric enzymes, and even those of intact NRPSs, upon production in a heterologous chassis. Our strategy provides facile options for the rational engineering of fungal NRPSs and for the combinatorial reprogramming of nonribosomal peptide production.

FBENet: Feature-Level Boosting Ensemble Network for Hashimoto's Thyroiditis Ultrasound Image Classification.

Distinguishing Hashimoto's thyroiditis (HT) lesions from ordinary thyroid tissues is difficult with ultrasound images. Challenges in achieving high performance of HT ultrasound image classification include the low resolution, blurred features and large area of irrelevant noise. To address these problems, we propose a Feature-level Boosting Ensemble Network (FBENet) for HT ultrasound image classification. Specifically, to capture the features of suspicious HT lesions efficiently, an Ensemble Feature Boosting Module (EFBM) is introduced into the feature-level ensemble to boost the blurred features. Then, the spatial attention mechanism is adopted in backbone models to improve the feature focusing performance and representation ability. Furthermore, feature-level ensemble technique is employed in the training process to achieve more comprehensive feature representation ability. Experimentally, FBENet was trained on 6,503 HT ultrasound images, and tested on 1,626 HT ultrasound images with 82.92% accuracy and 89.24% AUC on average.

Visual light flicker stimulation: enhancing alertness in sleep-deprived rats.

Introduction: In the evolving field of neurophysiological research, visual light flicker stimulation is recognized as a promising non-invasive intervention for cognitive enhancement, particularly in sleep-deprived conditions. Methods: This study explored the effects of specific flicker frequencies (40 Hz and 20-30 Hz random flicker) on alertness recovery in sleep-deprived rats. We employed a multidisciplinary approach that included behavioral assessments with the Y-maze, in vivo electrophysiological recordings, and molecular analyses such as c-FOS immunohistochemistry and hormone level measurements. Results: Both 40 Hz and 20-30 Hz flicker significantly enhanced behavioral performance in the Y-maze test, suggesting an improvement in alertness. Neurophysiological data indicated activation of neural circuits in key brain areas like the thalamus and hippocampus. Additionally, flicker exposure normalized cortisol and serotonin levels, essential for stress response and mood regulation. Notably, increased c-FOS expression in brain regions related to alertness and cognitive functions suggested heightened neural activity. Discussion: These findings underscore the potential of light flicker stimulation not only to mitigate the effects of sleep deprivation but also to enhance cognitive functions. The results pave the way for future translational research into light-based therapies in human subjects, with possible implications for occupational health and cognitive ergonomics.

PROX1 drives neuroendocrine plasticity and liver metastases in prostate cancer.

With the widespread use of anti-androgen therapy, such as abiraterone and enzalutamide, the incidence of neuroendocrine prostate cancer (NEPC) is increasing. NEPC is a lethal form of prostate cancer (PCa), with a median overall survival of less than one year after diagnosis. In addition to the common bone metastases seen in PCa, NEPC exhibits characteristics of visceral metastases, notably liver metastasis, which serves as an indicator of a poor prognosis clinically. Key factors driving the neuroendocrine plasticity of PCa have been identified, yet the underlying mechanism behind liver metastasis remains unclear. In this study, we identified PROX1 as a driver of neuroendocrine plasticity in PCa, responsible for promoting liver metastases. Mechanistically, anti-androgen therapy alleviates transcriptional inhibition of PROX1. Subsequently, elevated PROX1 levels drive both neuroendocrine plasticity and liver-specific transcriptional reprogramming, promoting liver metastases. Moreover, liver metastases in PCa induced by PROX1 depend on reprogrammed lipid metabolism, a disruption that effectively reduces the formation of liver metastases.

Recent Advances in Functional Hydrogel for Repair of Abdominal Wall Defects: A Review.

The abdominal wall plays a crucial role in safeguarding the internal organs of the body, serving as an essential protective barrier. Defects in the abdominal wall are common due to surgery, infection, or trauma. Complex defects have limited self-healing capacity and require external intervention. Traditional treatments have drawbacks, and biomaterials have not fully achieved the desired outcomes. Hydrogel has emerged as a promising strategy that is extensively studied and applied in promoting tissue regeneration by filling or repairing damaged tissue due to its unique properties. This review summarizes the five prominent properties and advances in using hydrogels to enhance the healing and repair of abdominal wall defects: (a) good biocompatibility with host tissues that reduces adverse reactions and immune responses while supporting cell adhesion migration proliferation; (b) tunable mechanical properties matching those of the abdominal wall that adapt to normal movement deformations while reducing tissue stress, thereby influencing regulating cell behavior tissue regeneration; (c) drug carriers continuously delivering drugs and bioactive molecules to sites optimizing healing processes enhancing tissue regeneration; (d) promotion of cell interactions by simulating hydrated extracellular matrix environments, providing physical support, space, and cues for cell migration, adhesion, and proliferation; (e) easy manipulation and application in surgical procedures, allowing precise placement and close adhesion to the defective abdominal wall, providing mechanical support. Additionally, the advances of hydrogels for repairing defects in the abdominal wall are also mentioned. Finally, an overview is provided on the current obstacles and constraints faced by hydrogels, along with potential prospects in the repair of abdominal wall defects.

Aerobic exercise-induced HIF-1α upregulation in heart failure: exploring potential impacts on MCT1 and MPC1 regulation.

BACKGROUND: The terminal stage of ischemic heart disease develops into heart failure (HF), which is characterized by hypoxia and metabolic disturbances in cardiomyocytes. The hypoxic failing heart triggers hypoxia-inducible factor-1α (HIF-1α) actions in the cells sensitized to hypoxia and induces metabolic adaptation by accumulating HIF-1α. Furthermore, soluble monocarboxylic acid transporter protein 1 (MCT1) and mitochondrial pyruvate carrier 1 (MPC1), as key nodes of metabolic adaptation, affect metabolic homeostasis in the failing rat heart. Aerobic exercise training has been reported to retard the progression of HF due to enhancing HIF-1α levels as well as MCT1 expressions, whereas the effects of exercise on MCT1 and MPC1 in HF (hypoxia) remain elusive. This research aimed to investigate the action of exercise associated with MCT1 and MPC1 on HF under hypoxia. METHODS: The experimental rat models are composed of four study groups: sham stented (SHAM), HF sedentary (HF), HF short-term exercise trained (HF-E1), HF long-term exercise trained (HF-E2). HF was initiated via left anterior descending coronary artery ligation, the effects of exercise on the progression of HF were analyzed by ventricular ultrasound (ejection fraction, fractional shortening) and histological staining. The regulatory effects of HIF-1α on cell growth, MCT1 and MPC1 protein expression in hypoxic H9c2 cells were evaluated by HIF-1α activatort/inhibitor treatment and plasmid transfection. RESULTS: Our results indicate the presence of severe pathological remodelling (as evidenced by deep myocardial fibrosis, increased infarct size and abnormal hypertrophy of the myocardium, etc.) and reduced cardiac function in the failing hearts of rats in the HF group compared to the SHAM group. Treadmill exercise training ameliorated myocardial infarction (MI)-induced cardiac pathological remodelling and enhanced cardiac function in HF exercise group rats, and significantly increased the expression of HIF-1α (p < 0.05), MCT1 (p < 0.01) and MPC1 (p < 0.05) proteins compared to HF group rats. Moreover, pharmacological inhibition of HIF-1α in hypoxic H9c2 cells dramatically downregulated MCT1 and MPC1 protein expression. This phenomenon is consistent with knockdown of HIF-1α at the gene level. CONCLUSION: The findings propose that long-term aerobic exercise training, as a non- pharmacological treatment, is efficient enough to debilitate the disease process, improve the pathological phenotype, and reinstate cardiac function in HF rats. This benefit is most likely due to activation of myocardial HIF-1α and upregulation of MCT1 and MPC1.

Identification of a Novel Chitinase from Bacillus paralicheniformis: Gene Mining, Sequence Analysis, and Enzymatic Characterization.

In this study, a novel strain for degrading chitin was identified as Bacillus paralicheniformis HL37, and the key chitinase CH1 was firstly mined through recombinant expression in Bacillus amyloliquefaciens HZ12. Subsequently, the sequence composition and catalytic mechanism of CH1 protein were analyzed. The molecular docking indicated that the triplet of Asp526, Asp528, and Glu530 was a catalytic active center. The enzymatic properties analysis revealed that the optimal reaction temperature and pH was 65 °C and 6.0, respectively. Especially, the chitinase activity showed no significant change below 55 °C and it could maintain over 60% activity after exposure to 85 °C for 30 min. Moreover, the optimal host strain and signal peptide were obtained to enhance the expression of chitinase CH1 significantly. As far as we know, it was the first time finding the highly efficient chitin-degrading enzymes in B. paralicheniformis, and detailed explanations were provided on the catalytic mechanism and enzymatic properties on CH1.

Atorvastatin, etanercept and the nephrogenic cardiac sympathetic remodeling in chronic renal failure rats.

BACKGROUND: Chronic renal failure (CRF) patients are predisposed to arrhythmias, while the detailed mechanisms are unclear. We hypothesized the chronic inflammatory state of CRF patients may lead to cardiac sympathetic remodeling, increasing the incidence of ventricular arrhythmia (VA) and sudden cardiac death. And explored the role of atorvastatin and etanercept in this process. METHODS: A total of 48 rats were randomly divided into sham operation group (Sham group), CRF group, CRF + atorvastatin group (CRF + statin group), and CRF + etanercept group (CRF + rhTNFR-Fc group). Sympathetic nerve remodeling was assessed by immunofluorescence of growth-associated protein 43 (GAP-43) and tyrosine hydroxylase positive area fraction. Electrophysiological testing was performed to assess the incidence of VA by assessing the ventricular effective refractory period and ventricular fibrillation threshold. The levels of tumor necrosis factor-alpha (TNF-α) and interleukin-1beta were determined by Western blotting and enzyme-linked immunosorbent assay. RESULTS: Echocardiogram showed that compared with the Sham group, left ventricular end-systolic diameter and ventricular weight/body weight ratio were significantly higher in the CRF group. Hematoxylin-eosin and Masson staining indicated that myocardial fibers were broken, disordered, and fibrotic in the CRF group. Western blotting, enzyme-linked immunosorbent assay, immunofluorescence and electrophysiological examination suggested that compared with the Sham group, GAP-43 and TNF-α proteins were significantly upregulated, GAP-43 and tyrosine hydroxylase positive nerve fiber area was increased, and ventricular fibrillation threshold was significantly decreased in the CRF group. The above effects were inhibited in the CRF + statin group and the CRF + rhTNFR-Fc group. CONCLUSIONS: In CRF rats, TNF-α was upregulated, cardiac sympathetic remodeling was more severe, and the nephrogenic cardiac sympathetic remodeling existed. Atorvastatin and etanercept could downregulate the expression of TNF-α or inhibit its activity, thus inhibited the above effects, and reduced the occurrence of VA and sudden cardiac death.

Effect of Poly(propylene carbonate) on Properties of Polylactic Acid-Based Composite Films.

To enrich the properties of polylactic acid (PLA)-based composite films and improve the base degradability, in this study, a certain amount of poly(propylene carbonate) (PPC) was added to PLA-based composite films, and PLA/PPC-based composite films were prepared by melt blending and hot-press molding. The effects of the introduction of PPC on the composite films were analyzed through in-depth studies on mechanical properties, water vapor and oxygen transmission rates, thermal analysis, compost degradability, and bacterial inhibition properties of the composite films. When the introduction ratio coefficient of PPC was 30%, the tensile strength of the composite film increased by 19.68%, the water vapor transmission coefficient decreased by 14.43%, and the oxygen transmission coefficient decreased by 18.31% compared to that of the composite film without PPC, the cold crystallization temperature of the composite film increased gradually from 96.9 °C to 104.8 °C, and PPC improved the crystallization ability of composite film. The degradation rate of the composite film with PPC increased significantly compared to the previous one, and the degradation rate increased with the increase in the PPC content. The degradation rate was 49.85% and 46.22% faster on average than that of the composite film without PPC when the degradation was carried out over 40 and 80 days; the composite film had certain inhibition, and the maximum diameter of the inhibition circle was 2.42 cm. This study provides a strategy for the development of PLA-based biodegradable laminates, which can promote the application of PLA-based laminates in food packaging.

Rising sun or strangled in the cradle？A narrative review of near-infrared fluorescence imaging-guided surgery for pancreatic tumors.

Near-infrared fluorescence (NIRF)-guided surgical navigation has become a promising and effective detection method in pancreatic tumor surgery. The imaging technique has gradually transitioned from the NIR-I region to the NIR-II region. Real-time assessment of the tumor boundary and determination of the ideal resection plane are essential for preserving the pancreatic parenchyma and its secretory functions. However, since the pancreatic parenchyma has a less rich blood supply than the liver, the application of contrast agents in pancreatic tumor surgery is still in its infancy. The application of indocyanine green (ICG) and methylene blue (MB) in intraoperative NIRF imaging of pancreatic tumors has become more mature, but due to the characteristics of non-specific imaging, the imaging efficiency and depth need to be improved. Many tumor-specific imaging agents have been designed, but most of them have not gone past animal trials because of their high development and imaging costs, biotoxicity, and other limitations. In this article, we review recent reports of ICG, MB and newly developed contrast agents and imaging devices. We focus on the current status and new developments in the application of these contrast agents and summarize the current clinical and preclinical studies on specific contrast agents. We synthesize relevant reports to discuss the difficulties and prospects of the application of fluorescent imaging agents in pancreatic tumors. We hope that reviewing previous studies and the current progress on contrast imaging technology will provide new perspectives for its future application and development in pancreatic tumor surgery, which should translate into better patient prognoses. The manuscript was written according to the Scale for the Assessment of Narrative Review Articles (SANRA).

Analysis of spatial and temporal changes in vegetation cover and its drivers in the Aksu River Basin, China.

Exploring vegetation dynamics in arid areas and their responses to different natural and anthropogenic factors is critical for understanding ecosystems. Based on the monthly MOD13Q1 (250 m) remote sensing data from 2000 to 2019, this study analyzed spatio-temporal changes in vegetation cover in the Aksu River Basin and predicted future change trends using one-dimensional linear regression, the Mann-Kendall test, and the Hurst index. Quantitative assessment of the magnitude of anthropogenic and natural drivers was performed using the Geodetector model. Eleven natural and anthropogenic factors were quantified and analyzed within five time periods. The influence of the driving factors on the changes in the normalized difference vegetation index (NDVI) in each period was calculated and analyzed. Four main results were found. (1) The overall vegetation cover in the region significantly grew from 2000 to 2019. The vegetation cover changes were dominated by expected future improvements, with a Hurst index average of 0.45. (2) Land use type, soil moisture, surface temperature, and potential vapor dispersion were the main drivers of NDVI changes, with annual average q-values above 0.2. (3) The driving effect of two-factor interactions was significantly greater than that of single factors, especially land use type interacts with other factors to a greater extent on vegetation cover. (4) The magnitude of the interaction between soil moisture and potential vapor dispersion and the magnitude of the interaction between anthropogenic factors and other factors showed an obvious increasing trend. Current soil moisture and human activities had a positive influence on the growth of vegetation in the area. The findings of this study are important for ecological monitoring and security as well as land desertification control.

Risk and prognosis of secondary lung cancer after radiation therapy for thoracic malignancies.

OBJECTIVE: Radiation therapy (RT) may increase the risk of second cancer. This study aimed to determine the association between exposure to radiotherapy for the treatment of thoracic cancer (TC) and subsequent secondary lung cancer (SLC). MATERIALS AND METHODS: The Surveillance, Epidemiology, and End Results (SEER) database (from 1975 to 2015) was queried for TC. Univariate Cox regression analyses and multiple primary standardized incidence ratios (SIRs) were used to assess the risk of SLC. Subgroup analyses of patients stratified by latency time since TC diagnosis, age at TC diagnosis, and calendar year of TC diagnosis stage were also performed. Overall survival and SLC-related death were compared among the RT and no radiation therapy (NRT) groups by using Kaplan-Meier analysis and competitive risk analysis. RESULTS: In a total of 329 129 observations, 147 847 of whom had been treated with RT. And 6799 patients developed SLC. Receiving radiotherapy was related to a higher risk of developing SLC for TC patients (adjusted HR, 1.25; 95% CI, 1.19-1.32; P < 0.001). The cumulative incidence of developing SLC in TC patients with RT (3.8%) was higher than the cumulative incidence (2.9%) in TC patients with NRT(P). The incidence risk of SLC in TC patients who received radiotherapy was significantly higher than the US general population (SIR, 1.19; 95% CI, 1.14-1.23; P < 0.050). CONCLUSIONS: Radiotherapy for TC was associated with higher risks of developing SLC compared with patients unexposed to radiotherapy.

Identification and epidemiology of a novel Hepacivirus in domestic ducks in Hunan province, China.

The genus Hepacivirus comprises a diverse range of genetically distinct viruses that infect both mammalian and non-mammalian hosts, with some posing significant risks to human and animal health. Members of the genus Hepacivirus are typically classified into fourteen species (Hepacivirus A-N), with ongoing discoveries of novel hepaciviruses like Hepacivirus P and Hepacivirus Q. In this study, a novel Hepacivirus was identified in duck liver samples collected from live poultry markets in Hunan province, China, using unbiased high-throughput sequencing and meta-transcriptomic analysis. Through sequence comparison and phylogenetic analysis, it was determined that this newly discovered Hepacivirus belongs to a new subspecies of Hepacivirus Q. Moreover, molecular screening revealed the widespread circulation of this novel virus among duck populations in various regions of Hunan province, with an overall prevalence of 13.3%. These findings significantly enhence our understanding of the genetic diversity and evolution of hepaciviruses, emphasizing the presence of genetically diverse hepaciviruses duck populations in China. Given the broad geographical distribution and relatively high positive rate, further investigations are essential to explore any potential associations between Hepacivirus Q and duck-related diseases.

Pacing Strategies in Elite Individual-Medley Swimmers: A Decision-Tree Approach.

PURPOSE: This study aimed to examine pacing strategies and identify the stroke that has the most significant impact on overall performance in men's and women's 200-m and 400-m individual-medley events from 2000 to 2021. METHODS: The time in each lap and overall race was retrieved from the World Aquatics website. The standardized time for each stroke in individual medley was calculated by dividing the actual time by a reference time specific to each stroke. The reference time was derived from the respective laps in single-stroke finals in the 2017 World Swimming Championships. The decision-tree method was used for analysis. The dependent variables were qualified or nonqualified in heats and semifinals, and winning medals in finals. The independent variables were the ratio of standardized time in each stroke to the sum of standardized time in all 4 strokes. RESULTS: Swimmers who spent a higher ratio of standardized time in the butterfly stroke (>0.236-0.245) are associated with a higher likelihood of winning medals or qualifying for the next stage in most men's and women's 200-m and 400-m individual medley. Butterfly exhibited the highest normalized importance that distinguished medalists from nonmedalists in the finals. The front-crawl stroke is the second most important determinant in medalists in men's and women's 200-m individual medley, whereas backstroke and breaststroke were the second most important in men's and women's 400-m individual medley, respectively. CONCLUSION: Individual-medley swimmers who were excellent in butterfly and conserved energy in butterfly had a higher likelihood of success.

Association of inflammatory markers based on routine blood with prognosis in patients underwent percutaneous coronary intervention.

Inflammation contributes to the pathophysiological processes of coronary artery disease. We evaluated the association between inflammatory biomarkers, neutrophil-to-lymphocyte ratio (NLR), red cell distribution width (RDW), systemic inflammatory index, platelet-lymphocyte ratio, and 1-year all-cause mortality in patients underwent percutaneous coronary intervention (PCI). In this retrospective cohort, we consecutively enrolled 4651 patients who underwent PCI. Baseline demographic details, clinical data, and laboratory parameters on admission were analyzed. The primary outcome was 1-year all-cause mortality after PCI. We performed Cox regression and restricted cubic spline analysis to assessed the association between the inflammatory biomarkers and the clinical outcome. The area under the curve from receiver operating characteristic analysis was determined for the ability to classify mortality outcomes. A total of 4651 patients were included. Of these, 198 (4.26%) died on follow-up. Univariate Cox regression showed that NLR (heart rate [HR]: 1.070, 95% confidence interval [CI]: 1.060-1.082, P < .001), RDW (HR: 1.441, 95% CI 1.368-1.518, P < .001), systemic inflammatory index (HR: 1.000, 95% CI 1.000-3.180, P < .001), platelet-lymphocyte ratio (HR: 3.812, 95% CI 1.901-3.364, P < .001) were significant predictors of 1-year all-cause mortality. After adjusting for other confounders in multivariate analysis, NLR (HR: 01.038, 95% CI 1.022-1.054, P < .001) and RDW (HR: 1.437, 95% CI 1.346-1.535, P < .001) remained significant predictors. Restricted cubic spline analysis showed the relationship between RDW, NLR, and 1-year all-cause mortality was linear after adjusting for the covariables (P for non-linearity < 0.001). The multivariable adjusted model led to improvement in the area under the curve to 0.83 (P < .05). Nomogram was created to predict the probability of 1 year mortality. Among the laboratory indices, RDW and NLR showed the best performance for mortality risk prediction. Multivariate predictive models significantly improved risk stratification.

Investigation into the characteristics of electron beam-aged microplastics and adsorption behavior of dibutyl phthalate.

Microplastics are increasingly prevalent in the environment, and their ability to adsorb various organic additives, posing harm to organisms, has attracted growing attention. Currently, there are no effective methods to age microplastics, and there is limited discussion on the subsequent treatment of aged microplastics. This study focuses on micro polyethylene (PE) and employs electron beam technology for aging treatment, investigating the adsorption and leaching behavior between PE and dibutyl phthalate (DBP) before and after aging. Experimental results indicate that with increasing doses of electron beam irradiation, the surface microstructure of PE worsens, inducing the generation of oxygen-containing functional groups on the surface of polyethylene. Comparative evaluations between electron beam aging and existing methods show that electron beam technology surpasses existing aging methods, achieving a level of aging exceeding 0.7 within an extremely short period of 1 min at doses exceeding 350 kGy. Adsorption experiments demonstrate that the adsorption between PE and DBP conforms to pseudo-second-order kinetics and the Freundlich model both before and after aging. The adsorption capacity of microplastics for DBP increases from 76.8 mg g-1 to 167.0 mg g-1 after treatment, exceeding that of conventional DBP adsorbents. Electron beam irradiation causes aging of microplastics mainly through the generation of ·OH, which lead to the formation of oxygen-containing functional groups on the microplastics' surface, thereby enhancing their adsorption capacity for DBP. This provides a new perspective for the degradation of aged microplastics and composite pollutants.

Flexible DNA Nanoclaws Offer Multivalent and Powerful Spatial Pattern-Recognition for Tumor Cells.

Multivalent receptor-ligand interactions (RLIs) exhibit excellent affinity for binding when targeting cell membrane receptors with low expression. However, existing strategies only allow for limited control of the valency and spacing of ligands for a certain receptor, lacking recognition patterns for multiple interested receptors with complex spatial distributions. Here, we developed flexible DNA nanoclaws with multivalent aptamers to achieve powerful cell recognition by controlling the spacing of aptamers to match the spatial patterns of receptors. The DNA nanoclaw with spacing-controllable binding sites was constructed via hybrid chain reaction (HCR), enabling dual targeting of HER2 and EpCAM molecules. The results demonstrate that the binding affinity of multivalent DNA nanoclaws to tumor cells is enhanced. We speculate that the flexible structure may conform better to irregularly shaped membrane surfaces, increasing the probability of intermolecular contact. The capture efficiency of circulating tumor cells successfully verified the high affinity and selectivity of this spatial pattern. This strategy will further promote the potential application of DNA frameworks in future disease diagnosis and treatment.

Hybrid Double-Sided Tape with Asymmetrical Adhesion and Burst Pressure Tolerance for Abdominal Injury Treatment.

Patients with open abdominal (OA) wounds have a mortality risk of up to 30%, and the resulting disabilities would have profound effects on patients. Here, we present a novel double-sided adhesive tape developed for the management of OA wounds. The tape features an asymmetrical structure and employs an acellular dermal matrix (ADM) with asymmetric wettability as a scaffold. It is constructed by integrating a tissue-adhesive hydrogel composed of polydopamine (pDA), quaternary ammonium chitosan (QCS), and acrylic acid cross-linking onto the bottom side of the ADM. Following surface modification with pDA, the ADM would exhibit characteristics resistant to bacterial adhesion. Furthermore, the presence of a developed hydrogel ensures that the tape not only possesses tissue adhesiveness and noninvasive peelability but also effectively mitigates damage caused by oxidative stress. Besides, the ADM inherits the strength of the skin, imparting high burst pressure tolerance to the tape. Based on these remarkable attributes, we demonstrate that this double-sided (D-S) tape facilitates the repair of OA wounds, mitigates damage to exposed intestinal tubes, and reduces the risk of intestinal fistulae and complications. Additionally, the D-S tape is equally applicable to treating other abdominal injuries, such as gastric perforations. It effectively seals the perforation, promotes injury repair, and prevents the formation of postoperative adhesions. These notable features indicate that the presented double-sided tape holds significant potential value in the biomedical field.

Genetic dissection of Brassica napus seed vigor after aging.

KEY MESSAGE: Stable and novel QTLs that affect seed vigor under different storage durations were discovered, and BnaOLE4, located in the interval of cqSW-C2-3, increased seed vigor after aging. Seed vigor is an important trait in crop breeding; however, the underlying molecular regulatory mechanisms governing this trait in rapeseed remain largely unknown. In the present study, vigor-related traits were analyzed in seeds from a doubled haploid (DH) rapeseed (Brassica napus) population grown in 2 different environments using seeds stored for 7, 5, and 3 years under natural storage conditions. A total of 229 quantitative trait loci (QTLs) were identified and were found to explain 3.78%-17.22% of the phenotypic variance for seed vigor-related traits after aging. We further demonstrated that seed vigor-related traits were positively correlated with oil content (OC) but negatively correlated with unsaturated fatty acids (FAs). Some pleiotropic QTLs that collectively regulate OC, FAs, and seed vigor, such as uq.A8, uq.A3-2, uq.A9-2, and uq.C3-1, were identified. The transcriptomic results from extreme pools of DH lines with distinct seed vigor phenotypes during accelerated aging revealed that various biological pathways and metabolic processes (such as glutathione metabolism and reactive oxygen species) were involved in seed vigor. Through integration of QTL analysis and RNA-Seq, a regulatory network for the control of seed vigor was constructed. Importantly, a candidate (BnaOLE4) from cqSW-C2-3 was selected for functional analysis, and transgenic lines overexpressing BnaOLE4 showed increased seed vigor after artificial aging. Collectively, these results provide novel information on QTL and potential candidate genes for molecular breeding for improved seed storability.

Multi-omics analysis of macrophage-associated receptor and ligand reveals a strong prognostic signature and subtypes in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a significant contributor to morbidity and mortality worldwide. The interaction between receptors and ligands is the primary mode of intercellular signaling and plays a vital role in the progression of HCC. This study aimed to identify the macrophage-related receptor ligand marker genes associated with HCC and further explored the molecular immune mechanisms attributed to altered biomarkers. Single-cell RNA sequencing data containing primary and recurrent samples were downloaded from the China National GeneBank. Cell types were first identified to explore differences between immune cells from different sample sources. CellChat analysis was used to infer and analyze intercellular communication networks quantitatively. Three molecular subtypes were constructed based on the screened twenty macrophage-associated receptor ligand genes. Bulk RNA-Seq data were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus databases. After the screening, the minor absolute shrinkage and selection operator (LASSO) regression model was employed to identify key markers. After collecting peripheral blood and clinical information from patients, an enzyme-linked immunosorbent assay (ELISA) was used to detect the correlation between key markers and IL-10, one of the macrophage markers. After developing a new HCC risk adjustment model and conducting analysis, it was found that there were significant differences in immune status and gene mutations between the high-risk and low-risk groups of patients based on macrophage-associated receptor and ligand genes. This study identified SPP1, ANGPT2, and NCL as key biological targets for HCC. The drug-gene interaction network analysis identified wortmannin, ribavirin, and tarnafloxin as potential therapeutic drugs for the three key markers. In a clinical cohort study, patients with immune checkpoint inhibitor (ICI) resistance had significantly higher expression levels of OPN, ANGPT2, NCL, and IL-10 than patients with ICI-responsiveness. These three key markers were positively correlated with the expression level of IL-10. The signature based on macrophage-associated receptor and ligand genes can accurately predict the prognosis of patients with HCC and the sensitivity to immunotherapy. These results may help guide the development of targeted prevention and personalized treatment of HCC.