Leucine restriction ameliorates Fusobacteriumnucleatum-driven malignant progression and radioresistance in nasopharyngeal carcinoma.

Radiotherapy resistance is the main cause of treatment failure among patients with nasopharyngeal carcinoma (NPC). Recently, increasing evidence has linked the presence of intratumoral Fusobacterium nucleatum (Fn) with the malignant progression and therapeutic resistance of multiple tumor types, but its influence on NPC has remained largely unknown. We found that Fn is prevalent in the tumor tissue of patients with NPC and is associated with radioresistance. Fn invaded and proliferated inside NPC cells and aggravated tumor progression. Mechanistically, Fn slowed mitochondrial dysfunction by promoting mitochondrial fusion and decreasing ROS generation, preventing radiation-induced oxidative damage. Fn inhibited PANoptosis by the SLC7A5/leucine-mTORC1 axis during irradiation stress, thus promoting radioresistance. Treatment with the mitochondria-targeted antibiotics or dietary restriction of leucine reduced intratumoral Fn load, resensitizing tumors to radiotherapy in vivo. These findings demonstrate that Fn has the potential to be a predictive marker for radioresistance and to help guide individualized treatment for patients with NPC.

Effects of total flavonoids of Rhizoma Drynariae on biochemical indicators of bone metabolism: a systematic review and meta-analysis.

Background: Evidence shows that the total flavonoids of Rhizoma Drynariae (TFRD) can improve bone mineral density (BMD). However, there is no evidence to summarize the improvement of biochemical indicators of bone metabolism (BIBM). Methods: The PubMed, Web of Science, Cochrane Library, Embase, Chinese National Knowledge Infrastructure (CNKI), Wanfang Database, Chongqing VIP Information Database (VIP) and SinoMed were searched from inception to 6 May 2024. The final included studies performed meta-analyses using RevMan 5.3. Results: Nine randomized controlled trials (RCTs) were ultimately included. The TFRD group had higher bone gla protein (BGP) and type I procollagen-N-propeptide (PINP) compared to the Other therapies (WMD: 5.11; 95% CI: 3.37, 6.84; p < 0.00001; WMD: 13.89; 95% CI: 11.81, 15.97; p < 0.00001). The tartrate-resistant acid phosphatase (TRACP) decreased significantly (WMD: -1.34; 95% CI: -1.62, -1.06; p < 0.00001). The alkaline phosphatase (ALP) increased significantly (WMD: 7.47; 95% CI: 6.29, 8.66; p < 0.00001). There were no significant differences in serum calcium (SC) or serum phosphorus (SP) levels between the TFRD and control groups (WMD: 0.08; 95% CI: -0.04, 0.20; p = 0.17; WMD: 0.02; 95% CI: -0.02, 0.05; p = 0.36). Conclusion: TFRD can stimulate bone formation and prevent bone resorption in osteoporosis (OP) patients, but it has no effect on SC and SP. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/.

Acute effects of TLR3 agonist Poly(I:C) on bone marrow hematopoietic progenitor cells in mice.

Hematopoietic progenitor cells (HPCs) in bone marrow with limited abilities for self-renewal and differentiation continuously supply hematopoietic cells through life. When suffering infection or inflammation, HPCs will actively proliferate to provide differentiated hematopoietic cells to maintain hematopoietic homeostasis. Poly(I:C), an agonist of TLR3, can specifically activate Type I interferon (IFN-I) signaling which exerts anti-inflammatory effects and influence hematopoiesis after infection. However, the effects of Poly(I:C)-induced IFN-I on the bone marrow hematopoietic system still deserve attention. In this study, our results revealed the efficacy of the IFN-I model, with a remarkably decrease in HPCs and a sharp elevation in LSKs numbers after single dose of Poly(I:C) injection. Apoptotic ratios of HPCs and LSKs significantly increased 48 h after Poly(I:C) treatment. Application of Poly(I:C) prompted the transition of HPCs and LSKs from G0 to G1 phases, potentially leading to the accelerated exhaustion of HPCs. From the cobblestone area-forming cell (CAFC) assay, we speculate that Poly(I:C) impairs the differentiation capacity of HPCs as well as their colony-forming ability. RT-qPCR and immunohistochemistry revealed significant upregulation of IFN-I associated genes and proteins following Poly(I:C) treatment. In conclusion, a single dose of Poly(I:C) induced an acute detrimental effect on HPCs within 48 h potentially due to TLR3 engagement. This activation cascaded into a robust IFN-I response emanating from the bone marrow, underscoring the intricate immunological dynamics at play following Poly(I:C) intervention.

In Vitro Simulated Ketogenic Diet Inhibits the Proliferation and Migration of Liver Cancer Cells by Reducing Insulin Production and Down-regulating FOXC2 Expression.

Ketogenic diet (KD) may benefit patients with liver cancer, but the underlying mechanism of its anti-cancer effect remains an open issue. This work aimed to explore the influence of simulated KD on the proliferation and migration of cultured hepatoma cells. The low-glucose medium supplemented with ß-hydroxybutyrate (BHB-Glow) was utilized to simulate clinical KD treatment. Western blot was utilized for detecting the expression of glycolysis-related proteins, Seahorse XF96 for oxygen consumption rate (OCR) and extracellular acidification rate (ECAR), and ELISA for insulin content. Expression of FOXC2 in liver cancer cells was analyzed by bioinformatics and qPCR. Cell Count Kit-8 (CCK-8) testing kit was utilized for testing cell viability. KD treatment significantly reduced the expression of glycolysis-related proteins in Huh-7 cells, inhibited insulin production in ß islet cells, reduced ECAR, and increased OCR. FOXC2 was significantly up-regulated in Huh-7 cell line, and sh-FOXC2 hindered the proliferation and migration of Huh-7 cells. The exogenous addition of insulin promoted the malignant progression of Huh-7 cells. Together, the medium simulating KD environment strengthened the protection of liver cancer cells by reducing insulin production and down-regulating FOXC2 expression. This study confirmed through in vitro cell experiments that KD could inhibit the proliferation and migration of liver cancer cells by targeting down regulation of insulin and FOXC2 expression, providing new theoretical basis for the treatment of liver cancer patients.

Apigenin ameliorates lupus nephritis by inhibiting SAT3 signaling in CD8+ T cells.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by widespread organ and tissue involvement, with lupus nephritis (LN) being one of its most severe complications. Dietary flavonoids, as for their anti-inflammatory and antioxidant properties, have shown therapeutic potential under various inflammatory conditions. Apigenin (AP) is one of the most studied phenolics and is found in many fruits, vegetables and herbs. This study aimed to investigate the therapeutic effects and underlying mechanisms of apigenin on LN. We evaluated the effects of apigenin on MRL/lpr mice, a well-established model for spontaneous LN. Apigenin treatment improved peripheral blood profiles, reduced serum inflammatory cytokines (IL-6, IFN-γ, IL-17, TGF-ß), lowered levels of autoantibodies (ANA, anti-dsDNA) and alleviated renal damage caused by autoantibodies and inflammatory cell infiltration. The results of immunohistochemistry and transcriptome analysis showed that AP could inhibit the infiltration of CD8+ cells in renal tissues. Single-cell sequencing public data from LN patients identified cytotoxic T lymphocytes (CTLs) as the primary CD8+ T cell subtype in the kidneys, with their differentiation regulated by STAT3. In this study, cell experiments demonstrated that AP can induce apoptosis in CD8+ T cells and reduce their recruitment of macrophages by inhibiting the STAT3/IL-17 signaling pathway. These findings highlight that a diet rich in dietary flavonoids, particularly apigenin, can offer therapeutic benefits for patients with SLE.

The study on circRNA profiling uncovers the regulatory function of the hsa_circ_0059665/miR-602 pathway in breast cancer.

Abnormal expression of circRNAs has been observed in different types of carcinomas, and they play significant roles in the biology of these cancers. Nevertheless, the clinical relevance and functional mechanisms of the majority of circRNAs implicated in breast cancer progression remain unclear. The primary objective of our investigation is to uncover new circRNAs in breast cancer and elucidate the underlying mechanisms by which they exert their effects. The circRNA expression profile data for breast cancer and RNA-sequencing data were acquired from distinct public databases. Differentially expressed circRNAs and mRNA were identified through fold change filtering. The establishment of the competing endogenous RNAs (ceRNAs) network relied on the interplay between circular RNAs, miRNAs, and mRNAs. The hub genes were identified from the protein-protein interaction (PPI) regulatory network using the CytoHubba plugin in Cytoscape. Moreover, the expression levels and prognostic value of these hub genes in the PPI network were assessed using the GEPIA and Kaplan-Meier plotter databases. Fluorescence in situ hybridization (FISH) was used to identified the expression and intracellular localization of hsa_circ_0059665 by using the tissue microarray. Transwell analysis and CCK-8 analysis were performed to assess the invasion, migration, and proliferation abilities of breast cancer cells. Additionally, we investigated the interactions between hsa_circ_0059665 and miR-602 through various methods, including FISH, RNA-binding protein immunoprecipitation (RIP), and luciferase reporter assay. Rescue experiments were conducted to determine the potential regulatory role of hsa_circ_0059665 in breast cancer progression. A total of 252 differentially expressed circRNAs were identified. Among them, 246 circRNAs were up-regulated, while 6 circRNAs were down-regulated. Based on prediction and screening of circRNA-miRNA and miRNA-mRNA binding sites, we constructed a network consisting of circRNA-miRNA-mRNA interactions. In addition, we constructed a Protein-Protein Interaction (PPI) network and identified six hub genes. Moreover, the expression levels of these six hub genes in breast cancer tissues were found to be significantly lower. Furthermore, the survival analysis results revealed a significant correlation between low expression levels of KIT, FGF2, NTRK2, CAV1, LEP and poorer prognosis in breast cancer patients. The FISH experiment results indicated that hsa_circ_0059665 exhibits significant downregulation in breast cancer, and its decreased expression is linked to poor prognosis in breast cancer patients. Functional in vitro experiments revealed that overexpression of hsa_circ_0059665 can inhibit proliferation, migration and invasion abilities of breast cancer cells. Further molecular mechanism studies showed that hsa_circ_0059665 exerts its anticancer gene role by acting as a molecular sponge for miR-602. In our study, we constructed and analyzed a circRNA-related ceRNA regulatory network and found that hsa_circ_0059665 can act as a sponge for miR-602 and inhibit the proliferation, invasion and migration of breast cancer cells.

Synergistic Sr Activation and Cr Buffering Effect on RuO2 Electronic Structures for Enhancing the Acidic Oxygen Evolution Reaction.

The oxygen evolution reaction (OER) performance of ruthenium-based oxides strongly correlates with the electronic structures of Ru. However, the widely adopted monometal doping method unidirectionally regulates only the electronic structures, often failing to balance the activity and stability. Here, we propose an "elastic electron transfer" strategy to achieve bidirectional optimization of the electronic structures of Sr, Cr codoped RuO2 catalysts for acidic OER. The introduction of electron-withdrawing Sr intrinsically activates the Ru sites by increasing the oxidation state of Ru. Simultaneously, Cr acts as an electron buffer, donating electrons to Ru in the presence of Sr in the as-prepared catalysts and absorbing excess electrons from Sr leaching during the OER. Such a bidirectional regulation feature of Cr prevents overoxidation of Ru and maintains its high oxidation state during the OER. The optimal Ru3Cr1Sr0.175 catalyst exhibits a low overpotential (214 mV @ 10 mA cm-2) and excellent stability (over 300 h).

Optically selective catalyst design with minimized thermal emission for facilitating photothermal catalysis.

Converting solar energy into fuels is pursued as an attractive route to reduce dependence on fossil fuel. In this context, photothermal catalysis is a very promising approach through converting photons into heat to drive catalytic reactions. There are mainly three key factors that govern the photothermal catalysis performance: maximized solar absorption, minimized thermal emission and excellent catalytic property of catalyst. However, the previous research has focused on improving solar absorption and catalytic performance of catalyst, largely neglected the optimization of thermal emission. Here, we demonstrate an optically selective catalyst based Ti3C2Tx Janus design, that enables minimized thermal emission, maximized solar absorption and good catalytic activity simultaneously, thereby achieving excellent photothermal catalytic performance. When applied to Sabatier reaction and reverse water-gas shift (RWGS) as demonstrations, we obtain an approximately 300% increase in catalytic yield through reducing the thermal emission of catalyst by ~70% under the same irradiation intensity. It is worth noting that the CO2 methanation yield reaches 3317.2 mmol gRu-1 h-1 at light power of 2 W cm-2, setting a performance record among catalysts without active supports. We expect that this design opens up a new pathway for the development of high-performance photothermal catalysts.

Downregulation of 4-HNE and FOXO4 collaboratively promotes NSCLC cell migration and tumor growth.

Non-small cell lung cancer (NSCLC) is among the most prevalent cancers and a leading cause of cancer-related mortality globally. Extracellular vesicles (EVs) derived from NSCLC play a pivotal role in lung cancer progression. Our findings reveal a direct correlation between the abundance of EVs and the transfection efficiencies. Co-culturing two different lung cancer cell lines could enhance EVs formation, cell proliferation, migration and tumorigenicity. mRNA chip and metabolic analyses revealed significant alterations in the FOXO signaling pathway and unsaturated fatty acid metabolism within tumor tissues derived from co-cultured cells. Shotgun lipidomics studies and bioinformatics analyses guided our attention towards 4-Hydroxynonenal (4-HNE) and FOXO4. Elevating 4-HNE or FOXO4 levels could reduce the formation of EVs and impede cell growth and migration. While silencing FOXO4 expression lead to an increase in cell cloning rate and enhanced migration. These findings suggest that regulating the production of 4-HNE and FOXO4 might provide an effective therapeutic approach for the treatment of NSCLC.

Associations of Socioeconomic Status Inequity with Incident Age-related Macular Degeneration in Middle-Aged and Elderly Population.

Background: The relationship between socioeconomic status (SES) inequity and incident age-related macular degeneration (AMD) remains unclear. We aim to investigate whether low SES increases the risk of AMD and to explore the effect of a healthy lifestyle on this association. Methods: This prospective cohort study included 316,663 UK Biobank individuals. SES inequity was identified via latent class analysis using education, household income, and occupational status. Healthy lifestyle score was calculated based on smoking, alcohol drinking, and physical activity (PA). Incident AMD was defined according to diagnosis records. Cox proportional hazards models were used to evaluate the relationship of low SES and AMD. Interrelationships of healthy lifestyle score on SES-AMD association were explored, including modification, mediation, and joint effects. Results: During the average 12.2 years of follow-up, 6,355 AMD cases were diagnosed. Participants with medium SES (hazard ratio: 1.10 [95% confidence interval (CI) 1.01 to 1.21]) and low SES (hazard ratio: 1.22 [95% CI 1.11 to 1.34]) had an increased risk of incident AMD compared to participants with high SES. PA significantly affected this association. Moreover, the association between low SES and AMD was significantly mediated (11.3%, 95% CI: 6.56 to 23.0) by smoking. Similarly, alcohol drinking suppressed (9.59%, 95% CI: 4.00 to 23.2) the association between high SES and AMD. Besides, a significant joint effect of SES and healthy lifestyle score was found. Conclusions: We provide further evidence for the relationship of socioeconomic inequity, healthy lifestyle, and incident AMD. Future public health strategies should aim to reduce socioeconomic inequity to prevent AMD.

Effects of Carbon/Kevlar Hybrid Ply and Intercalation Sequence on Mechanical Properties and Damage Resistance of Composite Laminates under Quasi-Static Indentation.

The investigation of damage development is essential for the design and optimization of hybrid structures. This paper provides a reference for the structural design of brittle-ductile hybrid LVI-resistant laminates through analyzing the damage development mechanism of carbon/Kevlar fabric-reinforced composite laminates. The effects of Kevlar fabric hybrid ply and intercalation on the damage development of carbon/Kevlar composite laminates under low-velocity impact (LVI) were investigated using quasi-static indentation (QSI). It was found that an increase in the Kevlar hybrid ratio significantly reduced the peak load and stiffness of these laminates (the maximum decreases in strength and stiffness were 46.03% and 41.43%, respectively), while laminates with identical hybrid ratios but different plying configurations maintained a comparable stiffness under QSI, with differences of less than 5%. Interestingly, Kevlar fibers exhibited irregular fractures as the yarn was splitting, while carbon fibers presented neat breaks, which indicated material-specific failure modes. Notably, the introduction of Kevlar hybridization beyond pure Kevlar configurations (KKKK) resulted in a decrease in the percentage of fiber damage (CCCC, CCCK, CCKK, and KCCK accounted for 80%, 79.8%, 70%, and 60% of fiber damage, respectively), attributed to an increase in resin cracks and lower levels of Kevlar yarn breakage. The internal damage diameter of specimens was accurately predicted from the diameter of visible damage on the QSI surface. Compared with CCCC and CCKK setups, which are affected by resin cracks formed via the carbon surface on the loading side propagating along the yarn direction (including the yarn settling direction), KCCK demonstrated less delamination between the first and second ply.

C5AR1-induced TLR1/2 pathway activation drives proliferation and metastasis in anaplastic thyroid cancer.

This study aimed to elucidate the role and mechanisms of Complement C5a receptor 1 (C5AR1) in driving the malignant progression of anaplastic thyroid carcinoma (ATC). C5AR1 expression was assessed in ATC tissues and cell lines. Functional assays evaluated the effects of C5AR1 knockdown on the malignant features of ATC cells. The interaction between C5AR1 and miR-335-5p was confirmed using a luciferase reporter assay and Fluorescence in situ hybridization, and the impact of C5AR1 knockdown on the Toll-like receptor (TLR) 1/2 signaling pathway was examined. In vivo studies evaluated the effects of C5AR1 modulation on tumor growth and metastasis. C5AR1 levels were elevated in ATC tumor samples and associated with poor survival in ATC patients. C5AR1 knockdown impeded ATC cell proliferation, migration, and invasion in vitro. MiR-335-5p was identified as an upstream regulator of C5AR1, which negatively modulates C5AR1 expression. C5AR1 knockdown diminished TLR1, TLR2, and myeloid differentiation primary response 88 (MyD88) levels, while C5AR1 overexpression activated this pathway. Blocking TLR1/2 signaling abrogated the oncogenic effects of C5AR1 overexpression. C5AR1 silencing inhibited tumor growth and lung metastasis of ATC cells in nude mice. C5AR1 contributes to ATC tumorigenesis and metastasis by activating the TLR1/2 pathway, and is negatively regulated by miR-335-5p. Targeting the miR-335-5p/C5AR1/TLR1/2 axis represents a potential therapeutic strategy for ATC.

KDM5A/B contribute to HIV-1 latent infection and survival of HIV-1 infected cells.

Combinational antiretroviral therapy (cART) suppresses human immunodeficiency virus type 1 (HIV-1) viral replication and pathogenesis in acquired immunodeficiency syndrome (AIDS) patients. However, HIV-1 remains in the latent stage of infection by suppressing viral transcription, which hinders an HIV-1 cure. One approach for an HIV-1 cure is the "shock and kill" strategy. The strategy focuses on reactivating latent HIV-1, inducing the viral cytopathic effect and facilitating the immune clearance for the elimination of latent HIV-1 reservoirs. Here, we reported that the H3K4 trimethylation (H3K4me3)-specific demethylase KDM5A/B play a role in suppressing HIV-1 Tat/LTR-mediated viral transcription in HIV-1 latent cells. Furthermore, we evaluated the potential of KDM5-specific inhibitor JQKD82 as an HIV-1 "shock and kill" agent. Our results showed that JQKD82 increases the H3K4me3 level at HIV-1 5' LTR promoter regions, HIV-1 reactivation, and the cytopathic effects in an HIV-1-latent T cell model. In addition, we identified that the combination of JQKD82 and AZD5582, a non-canonical NF-κB activator, generates a synergistic impact on inducing HIV-1 lytic reactivation and cell death in the T cell. The latency-reversing potency of the JQKD82 and AZD5582 pair was also confirmed in peripheral blood mononuclear cells (PBMCs) isolated from HIV-1 aviremic patients and in an HIV-1 latent monocyte. In latently infected microglia (HC69) of the brain, either deletion or inhibition of KDM5A/B results in a reversal of the HIV-1 latency. Overall, we concluded that KDM5A/B function as a host repressor of the HIV-1 lytic reactivation and thus promote the latency and the survival of HIV-1 infected reservoirs.

Association between low lung function and the increased risk of age-related macular degeneration: A population-based prospective cohort study.

Background: Low lung function is associated with an increased risk of age-related diseases. However, the relationship between age-related macular degeneration (AMD), the leading cause of blindness, and lung function remains unclear. We aimed to investigate whether low lung function increases the risk of AMD and the potential mechanisms behind this association. Methods: We conducted a prospective cohort analysis of 409 230 UK Biobank participants with completed lung function after excluding individuals with AMD. We used Cox proportional hazards models to estimate the risk of AMD incidence and mediation models to explore potential mechanisms driven by inflammatory markers, erythrocyte-related measures, and metabolites. Results: Overall, 6477 AMD cases were diagnosed across an average of 12.4 years of follow-up. Participants with low lung function had an increased risk of developing AMD compared to those with high lung function (forced vital capacity: adjusted hazard ratio (aHR) = 1.20 (95% confidence interval (CI) = 1.07-1.34); forced expiratory volume in one second: aHR = 1.32 (95% CI = 1.18-1.47); peak expiratory flow: aHR = 1.32 (95% CI = 1.20-1.45)). Inflammatory markers and erythrocyte-related measures mediated this relationship, acting as a pathway through which low lung function influenced AMD. The interactions of body mass index (BMI), sex, and smoking were significant and the effect of lung function on AMD was higher in men, obese, and smoking populations. Conclusions: The increased risk of AMD was associated with low lung function, with inflammatory and erythrocyte-related markers mediating this relationship. This suggests that improvements in lung function could reduce the risk of AMD, thereby promoting health and longevity.

Tailoring and understanding the lithium storage performance of triple-doped cobalt phosphide composites.

Cobalt phosphide (CoP) with high theoretical capacity as well as ceramic-like and metal-like properties is considered as a promising anode for lithium-ion batteries (LIBs). However, the large volume change and sluggish kinetic response limit its practical application. The optimization of composition, structural control and performance regulation of CoP electrodes can be achieved by the bottom-up assembly technique of metal-organic frameworks (MOFs). Due to the effective electronic regulation and lithiophilicity brought by the multiple heteroatoms doping and the synergistic effect of the unique structure derived from MOFs, the N, O, P triple-doped carbon and CoP composites (ZCP@NOP) exhibited excellent rate capability (554.61 mAh g-1 at 2 A g-1) and cycling stability (806.7 mAh g-1 after 500 cycles at 0.5 A g-1). The essence and evolution of lithium storage mechanism in CoP electrodes are also confirmed by the ex-situ techniques. The synergistic benefits of heteroatom co-doping carbon and cobalt phosphide, such as the decrease of the diffusion energy barrier of Li-ions and the optimization of electronic structures, are highlighted in theoretical calculations. In conclusion, new thoughts and ideas for the creation of future battery anode are provided by the combination of the N, O, P co-doping and the adaptable structural adjustment technique.

Seasonal effects of fish, seaweed and abalone cultures on dissolved organic matter and carbon sequestration potential in Sansha Bay, China.

Coastal bays serve as undeniable dissolved organic matter (DOM) reactors and the role of prevalent mariculture in DOM cycling deserves investigation. This study, based on four seasonal field samplings and a laboratory incubation experiment, examined the source and seasonal dynamics of DOM and fluorescent dissolved organic matter (FDOM) in the seawater of fish (Larimichthys crocea, LC), seaweed (Gracilaria lemaneiformis, GL) and abalone (Haliotis sp., HA) culturing zones in Sansha Bay, China. Using three-dimensional fluorescence spectroscopy coupled with parallel factor analysis (EEMs-PARAFAC), three fluorescent components were identified, i.e. protein-like C1, protein-like C2, and humic-like C3. Our results showed that mariculture activities dominated the DOM pool by seasonal generating abundant DOM with lower aromaticity and humification degrees. Accounting for 40-95 % of total fluorescent components, C1 (Ex/Em = 300/340 nm) was regarded the same as D1 (Ex/Em = 300/335 nm) identified in a 180-day degradation experiments of G. lemaneiformis detritus, indicating that the cultured seaweed modulated DOM through the seasonal production of C1. In addition, the incubation experiment revealed that 0.7 % of the total carbon content of seaweed detritus could be preserved as recalcitrant dissolved organic carbon (RDOC). However, fish culture appeared to contribute to liable DOC and protein-like C2, exerting a substantial impact on DOM during winter but making a negligible contribution to carbon sequestration, while abalone culture might promote the potential export and sequestration of seaweed-derived carbon to the ocean. Our results highlight the influences of mariculture activities, especially seaweed culture, in shaping DOM pool in coastal bays. These findings can provide reference for future studies on the carbon accounting of mariculture.

Exploring prognostic and immunological characteristics of pancreatic ductal adenocarcinoma through comprehensive genomic analysis of tertiary lymphoid structures and CD8 + T-cells.

PURPOSE: Tertiary lymphoid structures (TLSs) and CD8 + T-cells are potential prognostic indicators for pancreatic ductal adenocarcinoma (PDAC). We established a novel scoring system for evaluating the risk for PDAC based on TLS- and CD8 + T-cell-related genes. METHODS: We analyzed single-cell sequence data from PDAC patients in the Genome Sequence Archive. Bioinformatics and machine algorithms established and validated a scoring method (T-C score) based on PDAC survival-related genes highly expressed in TLSs and CD8 + T-cells. Patients were stratified into the low- and high-T-C score groups. Differences in survival, pathway enrichment, mutation status, immune cell infiltration, expression of immune checkpoint-associated genes, tumor stemness, and response to antitumor therapy were compared through computer simulation methods. RESULTS: Overall survival differed significantly between the training and validation cohorts' low- and high-T-C score groups. The low-T-C score group correlated with lower tumor mutation burden and lower levels of tumor stemness compared with the high-T-C score group. Patients with lower T-C scores exhibited advantages in immunotherapeutic responses and might be more sensitive to the chemotherapeutic regimen and multi-kinase inhibitors. CONCLUSION: The T-C score could serve as an effective model for predicting the survival and therapeutic responses of patients with PDAC.

Establishment and validation of an artificial intelligence-based model for real-time detection and classification of colorectal adenoma.

Colorectal cancer (CRC) prevention requires early detection and removal of adenomas. We aimed to develop a computational model for real-time detection and classification of colorectal adenoma. Computationally constrained background based on real-time detection, we propose an improved adaptive lightweight ensemble model for real-time detection and classification of adenomas and other polyps. Firstly, we devised an adaptive lightweight network modification and effective training strategy to diminish the computational requirements for real-time detection. Secondly, by integrating the adaptive lightweight YOLOv4 with the single shot multibox detector network, we established the adaptive small object detection ensemble (ASODE) model, which enhances the precision of detecting target polyps without significantly increasing the model's memory footprint. We conducted simulated training using clinical colonoscopy images and videos to validate the method's performance, extracting features from 1148 polyps and employing a confidence threshold of 0.5 to filter out low-confidence sample predictions. Finally, compared to state-of-the-art models, our ASODE model demonstrated superior performance. In the test set, the sensitivity of images and videos reached 87.96% and 92.31%, respectively. Additionally, the ASODE model achieved an accuracy of 92.70% for adenoma detection with a false positive rate of 8.18%. Training results indicate the effectiveness of our method in classifying small polyps. Our model exhibits remarkable performance in real-time detection of colorectal adenomas, serving as a reliable tool for assisting endoscopists.

Toward High Quality Multi-Object Tracking and Segmentation Without Mask Supervision.

Recently studies have shown the potential of weakly supervised multi-object tracking and segmentation, but the drawbacks of coarse pseudo mask label and limited utilization of temporal information remain to be unresolved. To address these issues, we present a framework that directly uses box label to supervise the segmentation network without resorting to pseudo mask label. In addition, we propose to fully exploit the temporal information from two perspectives. Firstly, we integrate optical flow-based pairwise consistency to ensure mask consistency across frames, thereby improving mask quality for segmentation. Secondly, we propose a temporally adjacent pair-based sampling strategy to adapt instance embedding learning for data association in tracking. We combine these techniques into an end-to-end deep model, named BoxMOTS, which requires only box annotation without mask supervision. Extensive experiments demonstrate that our model surpasses current state-of-the-art by a large margin, and produces promising results on KITTI MOTS and BDD100K MOTS. The source code is available at https://github.com/Spritea/BoxMOTS.

Sensitive sensing of GLA and ISL based on highly conductivity nitrogen-doped carbon synergistic dual-template molecularly imprinted ratiometric electrochemical sensor.

A novel ratiometric Molecularly Imprinted Electrochemical sensor for the specific marker of Glycyrrhiza glabra L. was developed in this work. To achieve simultaneous detection of two analytes on one sensor, we constructed a double template molecular imprinted electrochemical sensor with glabridin (GLA) and isoliquiritin (ISL) as templates. Further, Ferrocene/ZIF-8 (Fc/ZIF-8) composites were prepared via a one-pot solvothermal reaction and coated on the surface of a glassy carbon electrode (GCE), and the oxidation of Fc was presented as the internal reference signal. Nitrogen-doped carbon (NOC) with high conductivity was further loaded on the modified GCE. Based on theoretical exploration and computer directional simulation of density functional theory (DFT), the optimal functional monomer and the best ratio of double template molecules to functional monomer were screened. Under optimal conditions, the sensor produced electrochemical curves when exposed to a solution containing GLA and ISL. As the concentration of GLA and ISL increased, the peak current intensity of GLA and ISL (IGLA and IISL) also increased, while the peak current intensity of Fc (as a reference signal) remained relatively constant. The values of IGLA/IFc and IISL/IFc showed excellent linear relationships with GLA and ISL concentrations in the range of 0.1-160 µM and 0.5-150 µM, respectively. The detection limits were 0.052 µM and 0.27 µM (S/N = 3), respectively. Due to the imprinting effect of MIP and the existence of a reference signal, the sensor exhibited excellent selectivity and anti-interference ability and was successfully applied to the quality evaluation of Glycyrrhiza glabra L.