Research progress of migrasomes: from genesis to formation, physiology to pathology.

Migrasomes are recently identified organelles that form at the ends or forks of retraction fibers (RFs) behind migrating cells and are expelled from the cell through cell migration. Migrasomes contain signaling molecules which are captured by surrounding cells along with migrasomes or released into the extracellular environment following the rupture of the migrasomes. Finally, through the action of these signaling molecules, migrasomes facilitate the entire process of information conveyance. In addition, migrasomes also serves as a "scavenger" by removing damaged mitochondria from the cell to ensure cellular viability. Thus, migrasomes play a pivotal role in the integration of temporal, spatial, specific chemical information and the clearance of cellular harmful substances, critical for grasping migrasomes' functions. This review delves into the latest advancements in migrasomes research, covering aspects such as migrasomes' discovery, distribution, structure and characteristics, genesis and regulation mechanisms, and their correlation with diseases. Additionally, we scrutinize the present investigational findings on migrasomes within the cancer domain, examining their potential impact on cancer and prospective research avenues.

Different responses of taxonomic and functional trait structure of benthic macroinvertebrate assemblages to eutrophication in a large Chinese freshwater lake.

Functional trait measures have the potential to represent local habitat conditions and are considered promising tools for biomonitoring and bioassessment programs. Macroinvertebrates are an ecologically significant group in freshwater ecosystems and possess a range of functional traits which are employed to assess ecological quality. Nevertheless, the relationships between macroinvertebrate functional structure and anthropogenic disturbances remain poorly understood. In this study, we conducted a comparison of how functional trait-based and taxonomy-based composition of macroinvertebrate assemblages responded to eutrophication in Lake Taihu, a typical large eutrophic freshwater lake in China. Specifically, we examined both the taxonomy-based and trait-based compositions of benthic macroinvertebrates varied along the eutrophication gradient. Eutrophication was associated with remarkable decreases in the abundance of gastropod taxa and increases in Oligochaeta and Chironomidae. Ten categories belonging to six traits were significantly different among three site groups. The eutrophic and transition sites showed higher abundance of Size2, burrowers, and integument-respiration organisms than macrophytic sites, whereas abundance of Size1, conical-shaped, sprawlers, scrapers, and lung-respiration were higher in macrophytic sites. Both taxonomic (36.8%) and functional compositions (39.8%) of macroinvertebrate assemblages were influenced by the same variables: CODMn and transparency. Our study showed that macroinvertebrate trait-based approaches can be considered a useful supplement to traditional taxonomic approach for biomonitoring programs in freshwater lakes.

Machine learning developed a programmed cell death signature for predicting prognosis and immunotherapy benefits in lung adenocarcinoma.

BACKGROUND: Lung cancer is the leading cause of cancer-related deaths worldwide with poor prognosis. Programmed cell death (PCD) plays a crucial function in tumor progression and immunotherapy response in lung adenocarcinoma (LUAD). METHODS: Integrative machine learning procedure including 10 methods was performed to develop a prognostic cell death signature (CDS) using TCGA, GSE30129, GSE31210, GSE37745, GSE42127, GSE50081, GSE68467, GSE68571, and GSE72094 dataset. The correlation between CDS and tumor immune microenvironment was evaluated using various methods and single cell analysis. qRT-PCR and CCK-8 assay were conducted to explore the biological functions of hub gene. RESULTS: The prognostic CDS developed by Lasso + survivalSVM method was regarded as the optimal prognostic model. The CDS had a stable and powerful performance in predicting the clinical outcome of LUAD and served as an independent risk factor in TCGA and 8 GEO datasets. The C-index of CDS was higher than that of clinical stage and many developed signatures for LUAD. LUAD patients with low CDS score had a higher PD1&CTLA4 immunophenoscore, higher TMB score, lower TIDE score and lower tumor escape score, indicating a better immunotherapy benefit. Single cell analysis revealed a strong and frequent communication between epithelial cells and cancer-related fibroblasts by specific ligand-receptor pairs, including COL1A2-SDC4 and COL1A2-SDC1. Vitro experiment showed that SLC7A5 was upregulated in LUAD and knockdown of SLC7A5 obviously suppressed tumor cell proliferation. CONCLUSION: Our study developed a novel CDS for LUAD. The CDS served as an indicator for predicting the prognosis and immunotherapy benefits of LAUD patients.

Protective effect of L-theanine on carbon tetrachloride-induced acute liver injury in mice.

We studied effects of L-theanine, a unique amino acid in tea, on carbon tetrachloride (CCl(4))-induced liver injury in mice. The mice were pre-treated orally with L-theanine (50, 100 or 200 mg/kg) once daily for seven days before CCl(4) (10 ml/kg of 0.2% CCl(4) solution in olive oil) injection. L-theanine dose-dependently suppressed the increase of serum activity of ALT and AST and bilirubin level as well as liver histopathological changes induced by CCl(4) in mice. L-theanine significantly prevented CCl(4)-induced production of lipid peroxidation and decrease of hepatic GSH content and antioxidant enzymes activities. Our further studies demonstrated that L-theanine inhibited metabolic activation of CCl(4) through down-regulating cytochrome P450 2E1 (CYP2E1). As a consequence, L-theanine inhibited oxidative stress-mediated inflammatory response which included the increase of TNF-α and IL-1ß in sera, and expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in livers. CCl(4)-induced activation of apoptotic related proteins including caspase-3 and PARP in mouse livers was also prevented by L-theanine treatment. In summary, L-theanine protects mice against CCl(4)-induced acute liver injury through inhibiting metabolic activation of CCl(4) and preventing CCl(4)-induced reduction of anti-oxidant capacity in mouse livers to relieve inflammatory response and hepatocyte apoptosis.

Prognostic implications of an autophagy-based signature in colorectal cancer.

BACKGROUND: The heterogeneity of colorectal cancer (CRC) poses a significant challenge to the precise treatment of patients. CRC has been divided into 4 consensus molecular subtypes (CMSs) with distinct biological and clinical characteristics, of which CMS4 has the mesenchymal identity and the highest relapse rate. Autophagy plays a vital role in CRC development and therapeutic response. METHODS: The gene expression profiles collected from 6 datasets were applied to this study. Network analysis was applied to integrate the subtype-specific molecular modalities and autophagy signature to establish an autophagy-based prognostic signature for CRC (APSCRC). RESULTS: Network analysis revealed that 6 prognostic autophagy genes (VAMP7, DLC1, FKBP1B, PEA15, PEX14, and DNAJB1) predominantly regulated the mesenchymal modalities of CRC. The APSCRC was constructed by these 6 core genes and applied for risk calculation. Patients were divided into high- and low-risk groups based on APSCRC score in all cohorts. Patients within the high-risk group showed an unfavorable prognosis. In multivariate analysis, the APSCRC remained an independent predictor of prognosis. Moreover, the APSCRC achieved higher prognostic power than commercialized multigene signatures. CONCLUSIONS: We proposed and validated an autophagy-based signature, which is a promising prognostic biomarker of CRC patients. Further prospective studies are warranted to test and validate its efficiency for clinical application.

Integrated analysis identifies an immune-based prognostic signature for the mesenchymal identity in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) has been divided into 4 consensus molecular subtypes (CMSs), of which CMS4 has the mesenchymal identity and the highest relapse rate. Our goal is to develop a prognostic signature by integrating the immune system and mesenchymal modalities involved in CMS4. METHODS: The gene expression profiles collected from 5 public datasets were applied to this study, including 1280 samples totally. Network analysis was applied to integrate the mesenchymal modalities and immune signature to establish an immune-based prognostic signature for CRC (IPSCRC). RESULTS: We identified 6 immune genes as key factors of CMS4 and established the IPSCRC. The IPSCRC could significantly divide patients into high- and low- risk groups in terms of relapse-free survival (RFS) and overall survival (OS) and in discovery (RFS: P < .0001) and 4 independent validation sets (RFS range: P = .01 to <.0001; OS range: P = .02-.0004). After stage stratification, the IPSCRC could still distinguish poor prognosis patients in discovery (RFS: P = .04) and validation cohorts (RFS range: P = .04-.007) within stage II in terms of RFS. Further, in multivariate analysis, the IPSCRC remained an independent predictor of prognosis. Moreover, Macrophage M2 was significantly enriched in the high-risk group, while plasma cells enriched in the low-risk group. CONCLUSION: We propose an immune-based signature identified by network analysis, which is a promising prognostic biomarker and help for the selection of CRC patients who might benefit from more rigorous therapies. Further prospective studies are warranted to test and validate its efficiency for clinical application.

Toward Theoretically Cycling-Stable Lithium-Sulfur Battery Using a Foldable and Compositionally Heterogeneous Cathode.

Rechargeable lithium-sulfur (Li-S) batteries have been expected for new-generation electrical energy storages, which are attributed to their high theoretical energy density, cost effectiveness, and eco-friendliness. But Li-S batteries still have some problems for practical application, such as low sulfur utilization and dissatisfactory capacity retention. Herein, we designed and fabricated a foldable and compositionally heterogeneous three-dimensional sulfur cathode with integrated sandwich structure. The electrical conductivity of the cathode is facilitated by three different dimension carbons, in which short-distance and long-distance pathways for electrons are provided by zero-dimensional ketjen black (KB), one-dimensional activated carbon fiber (ACF) and two-dimensional graphene (G). The resultant three-dimensional sulfur cathode (T-AKG/KB@S) with an areal sulfur loading of 2 mg cm-2 exhibits a high initial specific capacity, superior rate performance and a reversible discharge capacity of up to 726 mAh g-1 at 3.6 mA cm-2 with an inappreciable capacity fading rate of 0.0044% per cycle after 500 cycles. Moreover, the cathode with a high areal sulfur loading of 8 mg cm-2 also delivers a reversible discharge capacity of 938 mAh g-1 at 0.71 mA cm-2 with a capacity fading rate of 0.15% per cycle and a Coulombic efficiency of almost 100% after 50 cycles.