Isolation of triazole-resistant Aspergillus fumigatus harbouring cyp51A mutations from five patients with invasive pulmonary aspergillosis in Yunnan, China.

Invasive aspergillosis (IA) is the most severe type of Aspergillus infection. Yunnan has developed agriculture, and the proportion of triazole-resistant A. fumigatus induced by triazole fungicides is much higher than that in other regions of China. Inhalation of triazole-resistant A. fumigatus is one of the main factors inducing IA. We gathered five strains of A. fumigatus from the sputum or bronchoalveolar lavage fluid (BALF) of patients with IA in Yunnan. Subsequent testing showed that all of these strains were resistant to triazoles and harboured mutations in the tandem repeat sequence of the cyp51A promoter region, suggesting that they may be triazole-resistant A. fumigatus present in the environment.

Effects of Sulfate Ions on Crude Oil Adsorption/Desorption on Carbonate Rocks: Experimental and Molecular Simulations.

In the background of the strong oil wettability and low production by water flooding in carbonate reservoirs, low-salinity water containing sulfate ions can significantly change the surface wettability of carbonate rocks and thus increase the sweeping area; however, the absorption and desorption mechanisms of the oil film in the carbonate rock surface remain unclear. This paper analyzed the wettability alternation of carbonate rocks' surface in pure water and sodium sulfate solution. At the same time, MD (Materials Studio) software was used to simulate the formation process of the oil film and the effect of sulfate ions on the desorption of the oil film on the surface of carbonate rocks. The experimental results showed that sodium sulfate solution could accelerate the rate from oil-wet to water-wet and the final contact angle (49°) was smaller than that in pure water. The simulation results showed that dodecane molecules moved to the surface of calcite to form a double layer of the oil film and that the oil film near the calcite surface had a high-density stable structure under the van der Waals and electrostatic action. The hydrating sulfate ions above the oil film broke through the double oil film to form a water channel mainly under the action of electrostatic force and a hydrogen bond and then adsorbed on the calcite surface. A large number of water molecules moved down the water channel based on a strong hydrogen bonding force and crowded out the oil molecules on the surface of the calcite, resulting in the oil film detachment. This work aims to explain the interaction of oil molecules, water molecules, and SO42- ions at the molecular scale and guide the practical application of low-salinity water flooding in carbonate reservoirs.

Systematical explorations of forensic feature and population genetic diversity of the Chinese Mongolian group from northwest China via a self-constructed Multi-InDel panel.

This study aimed to investigate the genetic polymorphisms and population characteristics of Chinese Mongolian group from northwest China (NCM) through a self-developed panel including 43 autosomal insertion/deletion (A-InDel) polymorphism genetic markers. Herein, 288 unrelated healthy individuals from the NCM group were employed to obtain the genetic data of 43 A-InDels through multiplex PCR amplification and InDel genotyping using capillary electrophoresis platform. In addition, multiplex population genetic analyses were performed between the NCM group and 27 reference populations. There were no deviations at 43 loci from Hardy-Weinberg equilibrium in the NCM group. The observed heterozygosity (Ho) values ranged from 0.312 8 to 0.559 2, and the combined power of discrimination (CPD) and cumulative probability of exclusion (CPE) values in the NCM group were 0.999 999 999 999 999 998 77 and 0.999 814, respectively. The forensic parameter values indicated that this panel was polymorphic and informative in the NCM group and could be used as an effective tool for forensic personal identification. Furthermore, the results of pairwise genetic distances, principal component analysis, multidimensional scaling analysis, phylogenetic tree construction, and admixture analysis among the NCM group and 27 reference populations revealed that there were closer genetic relationships between the NCM group and East Asian populations, especially Chinese Hui group (CHH) from the northwest China, which is consistent with the geographical location. These present findings contributed to the ongoing genetic explorations and insights into the genetic architecture of the NCM group.

Multifunctional fluorescent probe for simultaneous revealing Cys and ONOO- dynamic correlation in the ferroptosis.

Ferroptosis is a type of lipid peroxidation-induced apoptosis brought on by imbalances in iron metabolism and redox. It involves both the thiol-associated anti-ferroptosis pathway and the excessive buildup of reactive oxygen species (ROS), which stimulates the ferroptosis pathway. Determining the precise control mechanism of ferroptosis requires examining the dynamic connection between reactive sulfur species (RSS) and ROS. Cysteine (Cys) and peroxynitrite (ONOO-) are highly active redox species in organisms and play dynamic roles in the ferroptosis process. In this study, a coumarin dye was conjugated with specific response sites for Cys and ONOO-, enabling the simultaneous detection of Cys and ONOO- through the green and red fluorescence channels, respectively (λem = 498 nm for Cys and λem = 565 nm for ONOO-). Using the probe LXB, we monitored the changes in Cys and ONOO- levels in the ferroptosis pathway induced by erastin. The results demonstrate a significant generation of ONOO- and a noticeable decrease in intracellular Cys levels at the beginning upon erastin treatment and finally maintains a relatively low level. This study presents the first probe to investigate the intracellular redox modulation and control between Cys and ONOO- during ferroptosis, providing valuable insights into the potential mutual correlation between Cys and ONOO- in this process.

Swing Origami-Structure-Based Triboelectric Nanogenerator for Harvesting Blue Energy toward Marine Environmental Applications.

The appearance of triboelectric nanogenerators (TENG) provides a promising energy technology for harvesting abundant water wave energy. Here, the design and fabrication of a swinging origami-structured TENG (SO-TENG) tailored specifically for water wave energy harvesting are presented. The design incorporates an oscillating structure weighted at the bottom, inducing reciprocating motion propelled by the inertia of passing water waves. This reciprocating motion efficiently converts mechanical into electrical energy through the origami structure. By employing origami as the monomer structure, the surface contact area between friction layers is enhanced, thereby optimizing output performance. the swinging structure, combined with the placement of heavy objects, enhances the folding and contact of the origami, allowing it to operate effectively in low-frequency water wave environments. This configuration exhibits robust power generation capabilities, making it suitable for powering small electronic devices in water wave environments. Furthermore, when applied to metal corrosion protection, the SO-TENG demonstrates notable efficacy. Compared to exposed Q235 carbon steel, Q235 carbon steel protected by SO-TENG exhibits a significant reduction in open-circuit potential drop, approximately 155 mV, indicative of superior anti-corrosion properties. It lays a solid foundation for water wave energy collection and self-powered metal corrosion protection in marine environments.

Abnormal structural covariance networks in young adults with recent cannabis use.

BACKGROUND: Recent cannabis use (RCU) exerts adverse effects on the brain. However, the effect of RCU on structural covariance networks (SCNs) is still unclear. This retrospective cross-sectional study aimed to explore the effects of RCU on SCNs in young adults in terms of whole cerebral cortical thickness (CT) and cortical surface area (CSA). METHODS: A total of 117 participants taking tetrahydrocannabinol (RCU group) and 896 participants not using cannabis (control group) were included in this study. All participants underwent MRI scanning following urinalysis screening, after which FreeSurfer 5.3 was used to calculate the CT and CSA, and SCNs matrices were constructed by Brain Connectivity Toolbox. Subsequently, the global and nodal network measures of the SCNs were computed based on these matrices. A nonparametric permutation test was used to investigate the group differences by Matlab. RESULTS: Regarding global network measures of CT, young adults with RCU exhibited altered small-worldness (P = 0.020) and clustering coefficient (P = 0.031) compared to controls, whereas there were no significant group differences in terms of SCNs constructed with CSA. Additionally, SCNs based on CT and CSA displayed abnormal nodal degree, nodal efficiency, and nodal betweenness centrality in vital brain regions of the triple network, including the dorsolateral and ventrolateral prefrontal cortex, and anterior cingulate cortex. CONCLUSION: The effects of RCU on brain structure in young adults can be detected by SCNs, in which structural abnormalities in the triple network are dominant, indicating that RCU can be detrimental to brain function.

Type I interferons induce an epigenetically distinct memory B cell subset in chronic viral infection.

Memory B cells (MBCs) are key providers of long-lived immunity against infectious disease, yet in chronic viral infection, they do not produce effective protection. How chronic viral infection disrupts MBC development and whether such changes are reversible remain unknown. Through single-cell (sc)ATAC-seq and scRNA-seq during acute versus chronic lymphocytic choriomeningitis viral infection, we identified a memory subset enriched for interferon (IFN)-stimulated genes (ISGs) during chronic infection that was distinct from the T-bet+ subset normally associated with chronic infection. Blockade of IFNAR-1 early in infection transformed the chromatin landscape of chronic MBCs, decreasing accessibility at ISG-inducing transcription factor binding motifs and inducing phenotypic changes in the dominating MBC subset, with a decrease in the ISG subset and an increase in CD11c+CD80+ cells. However, timing was critical, with MBCs resistant to intervention at 4 weeks post-infection. Together, our research identifies a key mechanism to instruct MBC identity during viral infection.

BAF-Net: bidirectional attention-aware fluid pyramid feature integrated multimodal fusion network for diagnosis and prognosis.

OBJECTIVE: To go beyond the deficiencies of the three conventional multimodal fusion strategies (i.e., input-, feature- and output-level fusion), we propose a bidirectional attention-aware fluid pyramid feature integrated fusion network (BAF-Net) with cross-modal interactions for multimodal medical image diagnosis and prognosis. Approach: BAF-Net is composed of two identical branches to preserve the unimodal features and one bidirectional attention-aware distillation stream to progressively assimilate cross-modal complements and to learn supplementary features in both bottom-up and top-down processes. Fluid pyramid connections were adopted to integrate the hierarchical features at different levels of the network, and channel-wise attention modules were exploited to mitigate cross-modal cross-level incompatibility. Furthermore, depth-wise separable convolution was introduced to fuse the cross-modal cross-level features to alleviate the increase in parameters to a great extent. The generalization abilities of BAF-Net were evaluated in terms of two clinical tasks: (1) An in-house PET-CT dataset with 174 patients for differentiation between lung cancer and pulmonary tuberculosis. (2) A public multicenter PET-CT head and neck cancer dataset with 800 patients from nine centers for overall survival prediction. Main results: On the LC-PTB dataset, improved performance was found in BAF-Net (AUC = 0.7342) compared with input-level fusion model (AUC = 0.6825; p < 0.05), feature-level fusion model (AUC = 0.6968; p = 0.0547), output-level fusion model (AUC = 0.7011; p < 0.05). On the H&N cancer dataset, BAF-Net (C-index = 0.7241) outperformed the input-, feature-, and output-level fusion model, with 2.95%, 3.77%, and 1.52% increments of C-index (p = 0.3336, 0.0479 and 0.2911, respectively). The ablation experiments demonstrated the effectiveness of all the designed modules regarding all the evaluated metrics in both datasets. Significance: Extensive experiments on two datasets demonstrated better performance and robustness of BAF-Net than three conventional fusion strategies and PET or CT unimodal network in terms of diagnosis and prognosis.

Soft Actuator with Biomass Porous Electrode: A Strategy for Lowering Voltage and Enhancing Durability.

Electroactive artificial muscles with deformability have attracted widespread interest in the field of soft robotics. However, the design of artificial muscles with low-driven voltage and operational durability remains challenging. Herein, novel biomass porous carbon (BPC) electrodes are proposed. The nanoporous BPC enables the electrode to provide exposed active surfaces for charge transfer and unimpeded channels for ion migration, thus decreasing the driving voltage, enhancing time durability, and maintaining the actuation performances simultaneously. The proposed actuator exhibits a high displacement of 13.6 mm (bending strain of 0.54%) under 0.5 V and long-term durability of 99.3% retention after 550,000 cycles (∼13 days) without breaks. Further, the actuators are integrated to perform soft touch on a smartphone and demonstrated as bioinspired robots, including a bionic butterfly and a crawling robot (moving speed = 0.08 BL s-1). This strategy provides new insight into the design and fabrication of high-performance electroactive soft actuators with great application potential.

Posterior circulation ischemic stroke: radiomics-based machine learning approach to identify onset time from magnetic resonance imaging.

PURPOSE: Posterior circulation ischemic stroke (PCIS) possesses unique features. However, previous studies have primarily or exclusively relied on anterior circulation stroke cases to build machine learning (ML) models for predicting onset time. To date, there is no research reporting the effectiveness and stability of ML in identifying PCIS onset time. We aimed to build diffusion-weighted imaging-based ML models to identify the onset time of PCIS patients. METHODS: Consecutive PCIS patients within 24 h of definite symptom onset were included (112 in the training set and 49 in the independent test set). Images were processed as follows: volume of interest segmentation, image feature extraction, and feature selection. Five ML models, naïve Bayes, logistic regression, tree ensemble, k-nearest neighbor, and random forest, were built based on the training set to estimate the stroke onset time (binary classification: ≤ 4.5 h or > 4.5 h). Relative standard deviations (RSD), receiver operating characteristic (ROC) curves, and the calibration plot was performed to evaluate the stability and performance of the five models. RESULTS: The random forest model had the best performance in the test set, with the highest area under the curve (AUC, 0.840; 95% CI: 0.706, 0.974). This model also achieved the highest accuracy, sensitivity, specificity, positive predictive value, and negative predictive value (83.7%, 64.3%, 91.4%, 75.0%, and 86.5%, respectively). Furthermore, the model had high stability (RSD = 0.0094). CONCLUSION: The PCIS case-based ML model was effective for estimating the symptom onset time and achieved considerably high specificity and stability.

Tertiary lymphoid structural heterogeneity determines tumour immunity and prospects for clinical application.

Tertiary lymphoid structures (TLS) are clusters of immune cells that resemble and function similarly to secondary lymphoid organs (SLOs). While TLS is generally associated with an anti-tumour immune response in most cancer types, it has also been observed to act as a pro-tumour immune response. The heterogeneity of TLS function is largely determined by the composition of tumour-infiltrating lymphocytes (TILs) and the balance of cell subsets within the tumour-associated TLS (TA-TLS). TA-TLS of varying maturity, density, and location may have opposing effects on tumour immunity. Higher maturity and/or higher density TLS are often associated with favorable clinical outcomes and immunotherapeutic response, mainly due to crosstalk between different proportions of immune cell subpopulations in TA-TLS. Therefore, TLS can be used as a marker to predict the efficacy of immunotherapy in immune checkpoint blockade (ICB). Developing efficient imaging and induction methods to study TA-TLS is crucial for enhancing anti-tumour immunity. The integration of imaging techniques with biological materials, including nanoprobes and hydrogels, alongside artificial intelligence (AI), enables non-invasive in vivo visualization of TLS. In this review, we explore the dynamic interactions among T and B cell subpopulations of varying phenotypes that contribute to the structural and functional diversity of TLS, examining both existing and emerging techniques for TLS imaging and induction, focusing on cancer immunotherapies and biomaterials. We also highlight novel therapeutic approaches of TLS that are being explored with the aim of increasing ICB treatment efficacy and predicting prognosis.

Specific mortality in patients with diffuse large B-cell lymphoma: a retrospective analysis based on the surveillance, epidemiology, and end results database.

BACKGROUND: The full potential of competing risk modeling approaches in the context of diffuse large B-cell lymphoma (DLBCL) patients has yet to be fully harnessed. This study aims to address this gap by developing a sophisticated competing risk model specifically designed to predict specific mortality in DLBCL patients. METHODS: We extracted DLBCL patients' data from the SEER (Surveillance, Epidemiology, and End Results) database. To identify relevant variables, we conducted a two-step screening process using univariate and multivariate Fine and Gray regression analyses. Subsequently, a nomogram was constructed based on the results. The model's consistency index (C-index) was calculated to assess its performance. Additionally, calibration curves and receiver operator characteristic (ROC) curves were generated to validate the model's effectiveness. RESULTS: This study enrolled a total of 24,402 patients. The feature selection analysis identified 13 variables that were statistically significant and therefore included in the model. The model validation results demonstrated that the area under the receiver operating characteristic (ROC) curve (AUC) for predicting 6-month, 1-year, and 3-year DLBCL-specific mortality was 0.748, 0.718, and 0.698, respectively, in the training cohort. In the validation cohort, the AUC values were 0.747, 0.721, and 0.697. The calibration curves indicated good consistency between the training and validation cohorts. CONCLUSION: The most significant predictor of DLBCL-specific mortality is the age of the patient, followed by the Ann Arbor stage and the administration of chemotherapy. This predictive model has the potential to facilitate the identification of high-risk DLBCL patients by clinicians, ultimately leading to improved prognosis.

Prediction of mass spectrometry ionization efficiency based on COSMO-RS and machine learning algorithms.

Non-targeted analysis of high-resolution mass spectrometry (MS) can identify thousands of compounds, which also gives a huge challenge to their quantification. The aim of this study is to investigate the impact of mass spectrometry ionization efficiency on various compounds in food at different solvent ratios and to develop a predictive model for mass spectrometry ionization efficiency to enable non-targeted quantitative prediction of unknown compounds. This study covered 70 compounds in 14 different mobile phase ratio environments in positive ion mode to analyze the rules of the matrix effect. With the organic phase ratio from low to high, most compounds changed by 1.0 log units in log IE. The addition of formic acid enhanced the signal but also promoted the matrix effect, which often occurred in compounds with strong ionization capacity. It was speculated that the matrix effect was mainly in the form of competitive charge and charged droplet' gasification sites during MS detection. Subsequently, we present a log IE prediction method built using the COSMO-RS software and the artificial neural network (ANN) algorithm to address this difficulty and overcome the shortcomings of previous models, which always ignore the matrix effect. This model was developed following the principles of QSAR modeling recommended by the Organization for Economic Cooperation and Development (OECD). Furthermore, we validated this approach by predicting the log IE of 70 compounds, including those not involved in the log IE model development. The results presented demonstrate that the method we put forward has an excellent prediction accuracy for log IE (R2pred = 0.880), which means that it has the potential to predict the log IE of new compounds without authentic standards.

The nutritional profile of chia seeds and sprouts: tailoring germination practices for enhancing health benefits-a comprehensive review.

Chia seeds have gained significant attention due to their unique composition and potential health benefits, including high dietary fibers, omega-3 fatty acids, proteins, and phenolic compounds. These components contribute to their antioxidant, anti-inflammatory effects, as well as their ability to improve glucose metabolism and dyslipidemia. Germination is recognized as a promising strategy to enhance the nutritional value and bioavailability of chia seeds. Chia seed sprouts have been found to exhibit increased essential amino acid content, elevated levels of dietary fiber and total phenols, and enhanced antioxidant capability. However, there is limited information available concerning the dynamic changes of bioactive compounds during the germination process and the key factors influencing these alterations in biosynthetic pathways. Additionally, the influence of various processing conditions, such as temperature, light exposure, and duration, on the nutritional value of chia seed sprouts requires further investigation. This review aims to provide a comprehensive analysis of the nutritional profile of chia seeds and the dynamic changes that occur during germination. Furthermore, the potential for tailored germination practices to produce chia sprouts with personalized nutrition, targeting specific health needs, is also discussed.

Viperin inhibits interferon-γ production to promote Mycobacterium tuberculosis survival by disrupting TBK1-IKKε-IRF3-axis and JAK-STAT signaling.

OBJECTIVES AND DESIGN: As an interferon-inducible protein, Viperin has broad-spectrum antiviral effects and regulation of host immune responses. We aim to investigate how Viperin regulates interferon-γ (IFN-γ) production in macrophages to control Mycobacterium tuberculosis (Mtb) infection. METHODS: We use Viperin deficient bone-marrow-derived macrophage (BMDM) to investigate the effects and machines of Viperin on Mtb infection. RESULTS: Viperin inhibited IFN-γ production in macrophages and in the lung of mice to promote Mtb survival. Further insight into the mechanisms of Viperin-mediated regulation of IFN-γ production revealed the role of TANK-binding kinase 1 (TBK1), the TAK1-dependent inhibition of NF-kappa B kinase-epsilon (IKKε), and interferon regulatory factor 3 (IRF3). Inhibition of the TBK1-IKKε-IRF3 axis restored IFN-γ production reduced by Viperin knockout in BMDM and suppressed intracellular Mtb survival. Moreover, Viperin deficiency activated the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway, which promoted IFN-γ production and inhibited Mtb infection in BMDM. Additionally, a combination of the anti-TB drug INH treatment in the absence of Viperin resulted in further IFN-γ production and anti-TB effect. CONCLUSIONS: This study highlights the involvement of TBK1-IKKε-IRF3 axis and JAK-STAT signaling pathways in Viperin-suppressed IFN-γ production in Mtb infected macrophages, and identifies a novel mechanism of Viperin on negatively regulating host immune response to Mtb infection.

Colorimetry/fluorescence dual-mode detection of Salmonella typhimurium based on a "three-in-one" nanohybrid with high oxidase-like activity for AIEgen.

A colorimetry/fluorescence dual-mode assay based on the aptamer-functionalized magnetic covalent organic framework-supported CuO and Au NPs (MCOF-CuO/Au@apt) was developed for Salmonella typhimurium (S. typhimurium) biosensing. The nanohybrid combined three functions in one: good magnetic separation characteristic, excellent oxidase-mimic activity for tetrap-aminophenylethylene (TPE-4A), and target recognition capability. The attachment of MCOF-CuO/Au@apt onto the surface of S. typhimurium resulted in a significant reduction in the oxidase-mimicking activity of the nanohybrid, which could generate dual-signal of colorimetry and fluorescence through the catalytic oxidation of TPE-4A. Based on this, S. typhimurium could be specifically detected in the linear ranges of 102- 106 CFU·mL-1 and 101- 106 CFU·mL-1, with LODs of 7.6 and 2.1 CFU·mL-1, respectively in colorimetry/fluorescence modes. Moreover, the smartphone and linear discrimination analysis-based system could be used for on-site and portable testing. In addition, this platform showed applicability in detecting S. typhimurium in milk, egg liquid and chicken samples.

Metabolomic insights into the effects of seasonal shifts on the dynamic variation of non-volatile compounds of abalone (Haliotis discus hannai).

Abalone (Haliotis spp.) is a shellfish known for its exceptional nutritional value and significant economic worth. This study investigated the dynamic characteristics of non-volatile compounds over a year, including metabolites, lipids, nucleotides, and free amino acids (FAAs), which determined the nutritional quality and flavor of abalone. 174 metabolites and 371 lipids were identified and characterized, while 20 FAAs and 11 nucleotides were quantitatively assessed. These non-volatile compounds of abalone were fluctuated with months variation, which was consistent with the fluctuations of environmental factors, especially seawater temperature. Compared with seasonal variation, gender had less influence on these non-volatiles. June and July proved to be the optimal harvesting periods for abalone, with the levels of overall metabolites, lipids, FAAs, and nucleotides in abalone exhibiting a higher value in June and July over a year. Intriguingly, taurine covered 60% of the total FAAs and abalone could be used as dietary taurine supplementation.

Spherical fluorinated covalent organic polymer for highly efficient and selective extraction of fipronil and its metabolites in soil.

Covalent organic polymers (COPs) have garnered considerable attention as promising adsorbents of online solid phase extraction (online SPE). Morphology modulation provides an appealing solution to enhance adsorption efficiency and reduce back-pressure in the absorbent. However, the synthesis of COPs with regular geometric shapes and specific adsorption selectivity remains challenging. In this study, a uniform spherical fluorinated COP (F-sCOP, average diameter: 2.14 µm) was successfully synthesized by Schiff base reaction of 1,3,5-triformylphoroglucinol (TP) and 2,2'-bis(trifluoromethyl)benzidine (TFMB). The F-sCOP had a large surface area (BET: 346.2 m2 g-1), remarkable enrichment capacity (enrichment factors: 186-782), high selectivity toward fipronil and its metabolites (adsorption efficiency >93.1%), and admirable service life (>60 times). Based on the adsorbent, a novel µ-matrix cartridge extraction-online-µ-solid phase extraction-high performance liquid chromatography-mass spectrometry (µ-MCE-online-µ-SPE-HPLC-MS) method was constructed and used to track trace fipronil and its metabolites in soil. The proposed method exhibited a wide linear range (0.05-1000 ng g-1), low quantitation limits (LOQs: 0.0027-0.011 ng g-1), high recoveries (90.1-119.6%) and good repeatability (RSD ≤10.5%, n = 3) for fipronil analysis. This study paves the way for pesticide analysis in soil risk assessment.

Therapy-induced senescent tumor cell-derived extracellular vesicles promote colorectal cancer progression through SERPINE1-mediated NF-κB p65 nuclear translocation.

BACKGROUND: Cellular senescence frequently occurs during anti-cancer treatment, and persistent senescent tumor cells (STCs) unfavorably promote tumor progression through paracrine secretion of the senescence-associated secretory phenotype (SASP). Extracellular vesicles (EVs) have recently emerged as a novel component of the SASP and primarily mediate the tumor-promoting effect of the SASP. Of note, the potential effect of EVs released from STCs on tumor progression remains largely unknown. METHODS: We collected tumor tissues from two cohorts of colorectal cancer (CRC) patients to examine the expression of p16, p21, and SERPINE1 before and after anti-cancer treatment. Cohort 1 included 22 patients with locally advanced rectal cancer (LARC) who received neoadjuvant therapy before surgical resection. Cohort 2 included 30 patients with metastatic CRC (mCRC) who received first-line irinotecan-contained treatment. CCK-8, transwell, wound-healing assay, and tumor xenograft experiments were carried out to determine the impacts of EVs released from STCs on CRC progression in vitro and in vivo. Quantitative proteomic analysis was applied to identify protein cargo inside EVs secreted from STCs. Immunoprecipitation and mass spectrometer identification were utilized to explore the binding partners of SERPINE1. The interaction of SERPINE1 with p65 was verified by co-immunoprecipitation, and their co-localization was confirmed by immunofluorescence. RESULTS: Chemotherapeutic agents and irradiation could potently induce senescence in CRC cells in vitro and in human CRC tissues. The more significant elevation of p16 and p21 expression in patients after anti-cancer treatment displayed shorter disease-free survival (DFS) for LARC or progression-free survival (PFS) for mCRC. We observed that compared to non-STCs, STCs released an increased number of EVs enriched in SERPINE1, which further promoted the progression of recipient cancer cells. Targeting SERPINE1 with a specific inhibitor, tiplaxtinin, markedly attenuated the tumor-promoting effect of STCs-derived EVs. Additionally, the patients with greater increment of SERPINE1 expression after anti-cancer treatment had shorter DFS for LARC or PFS for mCRC. Mechanistically, SERPINE1 bound to p65, promoting its nuclear translocation and subsequently activating the NF-κB signaling pathway. CONCLUSIONS: We provide the in vivo evidence of the clinical prognostic implications of therapy-induced senescence. Our results revealed that STCs were responsible for CRC progression by producing large amounts of EVs enriched in SERPINE1. These findings further confirm the crucial role of therapy-induced senescence in tumor progression and offer a potential therapeutic strategy for CRC treatment.

Identification of MATE Family and Characterization of GmMATE13 and GmMATE75 in Soybean's Response to Aluminum Stress.

The multidrug and toxic compound extrusion (MATE) proteins are coding by a secondary transporter gene family, and have been identified to participate in the modulation of organic acid exudation for aluminum (Al) resistance. The soybean variety Glycine max "Tamba" (TBS) exhibits high Al tolerance. The expression patterns of MATE genes in response to Al stress in TBS and their specific functions in the context of Al stress remain elusive. In this study, 124 MATE genes were identified from the soybean genome. The RNA-Seq results revealed significant upregulation of GmMATE13 and GmMATE75 in TBS upon exposure to high-dose Al3+ treatment and both genes demonstrated sequence homology to citrate transporters of other plants. Subcellular localization showed that both proteins were located in the cell membrane. Transgenic complementation experiments of Arabidopsis mutants, atmate, with GmMATE13 or GmMATE75 genes enhanced the Al tolerance of the plant due to citrate secretion. Taken together, this study identified GmMATE13 and GmMATE75 as citrate transporter genes in TBS, which could improve citrate secretion and enhance Al tolerance. Our findings provide genetic resources for the development of plant varieties that are resistant to Al toxicity.