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1.
MAbs ; 16(1): 2374607, 2024.
Article in English | MEDLINE | ID: mdl-38956880

ABSTRACT

Precise measurement of the binding activity changes of therapeutic antibodies is important to determine the potential critical quality attributes (CQAs) in developability assessment at the early stage of antibody development. Here, we report a surface plasmon resonance (SPR)-based relative binding activity method, which incorporates both binding affinity and binding response and allows us to determine relative binding activity of antibodies with high accuracy and precision. We applied the SPR-based relative binding activity method in multiple forced degradation studies of antibody developability assessment. The current developability assessment strategy provided comprehensive, precise characterization of antibody binding activity in the stability studies, enabling us to perform correlation analysis and establish the structure-function relationship between relative binding activity and quality attributes. The impact of a given quality attribute on binding activity could be confidently determined without isolating antibody variants. We identified several potential CQAs, including Asp isomerization, Asn deamidation, and fragmentation. Some potential CQAs affected binding affinity of antibody and resulted in a reduction of binding activity. Certain potential CQAs impaired antibody binding to antigen and led to a loss of binding activity. A few potential CQAs could influence both binding affinity and binding response and cause a substantial decrease in antibody binding activity. Specifically, we identified low abundance Asn33 deamidation in the light chain complementarity-determining region as a potential CQA, in which all the stressed antibody samples showed Asn33 deamidation abundances ranging from 4.2% to 27.5% and a mild binding affinity change from 1.76 nM to 2.16 nM.


Subject(s)
Antibodies, Monoclonal , Surface Plasmon Resonance , Surface Plasmon Resonance/methods , Humans , Antibodies, Monoclonal/chemistry , Antibodies, Monoclonal/immunology , Antibody Affinity , Protein Binding , Animals
2.
Front Immunol ; 15: 1416751, 2024.
Article in English | MEDLINE | ID: mdl-39040095

ABSTRACT

Tissue-resident memory T cells (TRM) are a specialized subset of long-lived memory T cells that reside in peripheral tissues. However, the impact of TRM-related immunosurveillance on the tumor-immune microenvironment (TIME) and tumor progression across various non-small-cell lung cancer (NSCLC) patient populations is yet to be elucidated. Our comprehensive analysis of multiple independent single-cell and bulk RNA-seq datasets of patient NSCLC samples generated reliable, unique TRM signatures, through which we inferred the abundance of TRM in NSCLC. We discovered that TRM abundance is consistently positively correlated with CD4+ T helper 1 cells, M1 macrophages, and resting dendritic cells in the TIME. In addition, TRM signatures are strongly associated with immune checkpoint and stimulatory genes and the prognosis of NSCLC patients. A TRM-based machine learning model to predict patient survival was validated and an 18-gene risk score was further developed to effectively stratify patients into low-risk and high-risk categories, wherein patients with high-risk scores had significantly lower overall survival than patients with low-risk. The prognostic value of the risk score was independently validated by the Cancer Genome Atlas Program (TCGA) dataset and multiple independent NSCLC patient datasets. Notably, low-risk NSCLC patients with higher TRM infiltration exhibited enhanced T-cell immunity, nature killer cell activation, and other TIME immune responses related pathways, indicating a more active immune profile benefitting from immunotherapy. However, the TRM signature revealed low TRM abundance and a lack of prognostic association among lung squamous cell carcinoma patients in contrast to adenocarcinoma, indicating that the two NSCLC subtypes are driven by distinct TIMEs. Altogether, this study provides valuable insights into the complex interactions between TRM and TIME and their impact on NSCLC patient prognosis. The development of a simplified 18-gene risk score provides a practical prognostic marker for risk stratification.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Memory T Cells , Tumor Microenvironment , Humans , Carcinoma, Non-Small-Cell Lung/immunology , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/genetics , Tumor Microenvironment/immunology , Tumor Microenvironment/genetics , Lung Neoplasms/immunology , Lung Neoplasms/mortality , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Prognosis , Memory T Cells/immunology , Immunologic Memory , Lymphocytes, Tumor-Infiltrating/immunology
3.
Syst Rev ; 13(1): 202, 2024 Jul 30.
Article in English | MEDLINE | ID: mdl-39080805

ABSTRACT

BACKGROUND: External cephalic version (ECV) is a medical procedure in which an extracorporeal manipulation is performed to render the breech presentation (BP) fetus in the cephalic position. The use of anesthesia to facilitate repositioning has been evaluated in various randomized clinical trials (RCTs), but its potential effectiveness remains controversial. METHODS: A systematic literature search was carried out in 8 electronic databases. In the meta-analysis, a random effects model was used to calculate the pooled relative risk (RR) and its 95% confidence interval (CI), and the pooled standardized mean difference (SMD) and its 95% CI, in order to systematically assess the effect of anesthesia on the success rates of ECV, vaginal delivery, cesarean delivery as well as other outcomes. Relevant subgroup analyses, publication bias test and sensitivity analyses were also conducted. RESULTS: This review included 17 RCTs. Women who received anesthesia had a significantly higher incidence of successful ECV (RR: 1.37, 95% CIs: 1.19-1.58) and vaginal delivery (RR: 1.23, 95% CIs: 1.03-1.47), and a significantly lower incidence of cesarean delivery (RR: 0.69, 95% CIs: 0.53-0.91), compared with those who did not. CONCLUSION: The administration of anesthesia not only significantly reduces maternal pain but also significantly increases the success rate of ECV in women with malpresentation at term, leading to a significant rise in the incidence of vaginal delivery. However, it may increase the incidence of maternal hypotension. SYSTEMATIC REVIEW REGISTRATION: The protocol was prospectively registered with PROSPERO, registration CRD42022381552.


Subject(s)
Breech Presentation , Cesarean Section , Version, Fetal , Female , Humans , Pregnancy , Anesthesia, Obstetrical/methods , Breech Presentation/therapy , Delivery, Obstetric/methods , Randomized Controlled Trials as Topic , Version, Fetal/methods
4.
Int J Biol Macromol ; : 134193, 2024 Jul 26.
Article in English | MEDLINE | ID: mdl-39069042

ABSTRACT

Long non-coding RNAs (lncRNAs) have been implicated in dilated cardiomyopathy (DCM). However, the biological functions and regulatory mechanisms underlying DCM remain elusive. Using a mouse model of experimental autoimmune myocarditis (EAM) to mimic DCM, we successfully constructed a dynamic lncRNA expression library for EAM by lncRNA microarray and found that the expression of a macrophage-enriched lncRNA, MAAMT, was significantly increased in the myocardial tissue of mice at the acute stage of EAM. Functionally, MAAMT knockdown alleviated the recruitment and proinflammatory activation of macrophages of heart, spleen, and peripheral blood of mice at the acute stage of EAM, reduced myocardial inflammation and injury, and eventually reversed ventricular remodelling and improved cardiac function in chronic EAM model mice. Mechanistically, we identified serine/arginine-rich splicing factor 1 (SRSF1) as an MAAMT-interacting protein in macrophages using RNA pull-down assays coupled with mass spectrometry. MAAMT knockdown attenuated the ubiquitination-mediated degradation of SRSF1, increased the protein expression of SRSF1, and restrained the activation of the NF-κB pathway in macrophages, thereby inhibiting the proinflammatory activation of macrophages. Collectively, our results demonstrate that MAAMT is a key proinflammatory regulator of myocarditis that promotes macrophage activation through the SRSF1-NF-κB axis, providing a new insight into early effective treatment strategies for DCM.

5.
Front Microbiol ; 15: 1403964, 2024.
Article in English | MEDLINE | ID: mdl-38903786

ABSTRACT

Beibu Gulf is an important semi-enclosed bay located in the northwestern South China Sea, and is famous for its high bio-productivity and rich bio-diversity. The fast development along the Beibu Gulf Economical Rim has brought pressure to the environment, and algal blooms occurred frequently in the gulf. In this study, surface water samples and micro-plankton samples (20-200 µm) were collected in the northern Beibu Gulf coast. Diversity and distribution of eukaryotic planktonic microalgae were analyzed by both metabarcoding and microscopic analyses. Metabarcoding revealed much higher diversity and species richness of microalgae than morphological observation, especially for dinoflagellates. Metabarcoding detected 144 microalgal genera in 8 phyla, while microscopy only detected 40 genera in 2 phyla. The two methods revealed different microalgal community structures. Dinoflagellates dominated in microalgal community based on metabarcoding due to their high copies of 18 s rRNA gene, and diatoms dominated under microscopy. Altogether 48 algal bloom and/or toxic species were detected in this study, 34 species by metabarcoding and 19 species by microscopy. Our result suggested a high potential risk of HABs in the Beibu Gulf. Microalgal community in the surface water samples demonstrated significantly higher OTU/species richness, alpha diversity, and abundance than those in the micro-plankton samples, although more HAB taxa were detected by microscopic observations in the micro-plankton samples. Furthermore, nano-sized taxa, such as those in chlorophytes, haptophytes, and chrysophyceans, occurred more abundantly in the surface water samples. This study provided a comprehensive morphological and molecular description of microalgal community in the northern Beibu Gulf.

6.
Antib Ther ; 7(2): 177-186, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38933532

ABSTRACT

Cancer immunotherapy represents a paradigm shift in oncology, offering a superior anti-tumor efficacy and the potential for durable remission. The success of personalized vaccines and cell therapies hinges on the identification of immunogenic epitopes capable of eliciting an effective immune response. Current limitations in the availability of immunogenic epitopes restrict the broader application of such therapies. A critical criterion for serving as potential cancer antigens is their ability to stably bind to the major histocompatibility complex (MHC) for presentation on the surface of tumor cells. To address this, we have developed a comprehensive database of MHC epitopes, experimentally validated for their MHC binding and cell surface presentation. Our database catalogs 451 065 MHC peptide epitopes, each with experimental evidence for MHC binding, along with detailed information on human leukocyte antigen allele specificity, source peptides, and references to original studies. We also provide the grand average of hydropathy scores and predicted immunogenicity for the epitopes. The database (MHCepitopes) has been made available on the web and can be accessed at https://github.com/jcm1201/MHCepitopes.git. By consolidating empirical data from various sources coupled with calculated immunogenicity and hydropathy values, our database offers a robust resource for selecting actionable tumor antigens and advancing the design of antigen-specific cancer immunotherapies. It streamlines the process of identifying promising immunotherapeutic targets, potentially expediting the development of effective antigen-based cancer immunotherapies.

7.
Adv Mater ; : e2403223, 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38896500

ABSTRACT

Incorporating passive radiative cooling and heating into personal thermal management has attracted tremendous attention. However, most current thermal management materials are usually monofunctional with a narrow temperature regulation range, and lack breathability, softness, and stretchability, resulting in a poor wearer experience and limited application scenarios. Herein, a breathable dual-mode leather-like nanotextile (LNT) with asymmetrical wrinkle photonic microstructures and Janus wettability for highly efficient personal thermal management is developed via a one-step electrospinning technique. The LNT is synthesized by self-bonding a hydrophilic cooling layer with welding fiber networks onto a hydrophobic photothermal layer, constructing bilayer wrinkle structures that offer remarkable optical properties, a wetting gradient, and unique textures. The resultant LNT exhibits efficient cooling capacity (22.0 °C) and heating capacity (22.1 °C) under sunlight, expanding the thermal management zone (28.3 °C wider than typical textiles). Additionally, it possesses favorable breathability, softness, stretchability, and sweat-wicking capability. Actual wearing tests demonstrate that the LNT can provide a comfortable microenvironment for the human body (1.6-8.0 °C cooler and 1.0-7.1 °C warmer than typical textiles) in changing weather conditions. Such a wearable dual-mode LNT presents great potential for personal thermal comfort and opens up new possibilities for all-weather smart clothing.

8.
Environ Sci Technol ; 58(28): 12477-12487, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-38943037

ABSTRACT

Although the impacts of exotic wetland plant invasions on native biodiversity, landscape features, and carbon-nitrogen cycles are well appreciated, biogeochemical consequences posed by ecological competition, such as the heterogeneity of dissolved organic matter (DOM) from plant detritus and its impact on the formation of reactive oxygen species, are poorly understood. Thus, this study delves into O2•- photogeneration potential of DOM derived from three different parts (stem, leaf, and panicle) of invasive Spartina alterniflora (SA) and native Phragmites australis (PA). It is found that DOM from the leaves of SA and the panicles of PA has a superior ability to produce O2•-. With more stable aromatic structures and a higher proportion of sulfur-containing organic compounds, SA-derived DOM generally yields more O2•- than that derived from PA. UVA exposure enhances the leaching of diverse DOM molecules from plant detritus. Based on the reported monitoring data and our findings, the invasion of SA is estimated to approximately double the concentration of O2•- in the surrounding water bodies. This study can help to predict the underlying biogeochemical impacts from the perspective of aquatic photochemistry in future scenarios of plant invasion, seawater intrusion, wetland degradation, and elevated solar UV radiation.


Subject(s)
Wetlands , Superoxides/metabolism , Introduced Species , Plants/metabolism
9.
Org Lett ; 26(26): 5472-5477, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38913068

ABSTRACT

Three dithio-fused boron dipyrromethenes (BODIPYs), DTFB-1, DTFB-2, and DTFB-3, in which symmetrically S-heteroaromatic ring units fused at [a], zigzag, and [b] bonds of the parent BODIPY core, respectively, were prepared from the facile and efficient post-functionalization of tetra-halogenated BODIPYs through Pd-catalyzed cyclization. Dithio-fusion at various positions of BODIPY effectively tunes their photophysical properties and single-crystal structural packing arrangements. The single-crystalline microribbons of DTFB-2 exhibit commendable hole mobilities in air, reaching up to 0.03 cm2 V-1 s-1.

11.
Appl Clin Genet ; 17: 71-84, 2024.
Article in English | MEDLINE | ID: mdl-38835974

ABSTRACT

Background: Charcot-Marie-Tooth disease (CMT) is a heterogeneous group of disorders involving peripheral nervous system. Charcot-Marie-Tooth disease 4B1 (CMT4B1) is a rare subtype of CMT. CMT4B1 is an axonal demyelinating polyneuropathy with an autosomal recessive mode of inheritance. Patients with CMT4B1 usually manifested with dysfunction of the motor and sensory systems which leads to gradual and progressive muscular weakness and atrophy, starting from the peroneal muscles and finally affecting the distal muscles. Germline mutations in MTMR2 gene causes CMT4B1. Material and Methods: In this study, we investigated a 4-year-old Chinese boy with gradual and progressive weakness and atrophy of both proximal and distal muscles. The proband's parents did not show any abnormalities. Whole-exome sequencing and Sanger sequencing were performed. Results: Whole-exome sequencing identified a novel homozygous nonsense mutation (c.118A>T; p.Lys40*) in exon 2 of MTMR2 gene in the proband. This novel mutation leads to the formation of a truncated MTMR2 protein of 39 amino acids instead of the wild- type MTMR2 protein of 643 amino acids. This mutation is predicted to cause the complete loss of the PH-GRAM domain, phosphatase domain, coiled-coil domain, and PDZ-binding motif of the MTMR2 protein. Sanger sequencing revealed that the proband's parents carried the mutation in a heterozygous state. This mutation was absent in 100 healthy control individuals. Conclusion: This study reports the first mutation in MTMR2 associated with CMT4B1 in a Chinese population. Our study also showed the importance of whole-exome sequencing in identifying candidate genes and disease-causing variants in patients with CMT4B1.

12.
Front Cardiovasc Med ; 11: 1378655, 2024.
Article in English | MEDLINE | ID: mdl-38826818

ABSTRACT

Primary myxofibrosarcoma of the heart, a rare cardiac malignancy, was diagnosed in a middle-aged female patient exhibiting progressive dyspnea following transthoracic echocardiography and pathological analysis. Postoperatively, the patient underwent chemotherapy and Lenvatinib mesylate therapy, with regular check-ups confirming her survival. After 10 months the patient is still alive and well.

13.
Sci Total Environ ; 946: 174187, 2024 Oct 10.
Article in English | MEDLINE | ID: mdl-38936741

ABSTRACT

Nutrient requirement for crop growth, defined as the amount of nutrient that crops take up from soil to produce a specific grain yield, is a key parameter in determining fertilizer application rate. However, existing studies primarily focus on identifying nitrogen (N), phosphorus (P), and potassium (K) requirements solely in relation to grain yield, neglecting grain protein content, a crucial index for wheat grain quality. Addressing this gap, we conducted multi-site, multi-cultivar, and multi-year field trials across three ecological regions of China from 2016 to 2020 to elucidate variations in nutrient requirements for grain yield and grain protein. The research findings revealed that wheat grain yield ranged from 4.1 to 9.3 Mg ha-1 (average 6.9 Mg ha-1) and grain protein content ranged from 98 to 157 g kg-1 (average 127 g kg-1) across the three regions. Notably, the N requirement exhibited a nonlinear correlation with the wheat grain yield but a linear increase with increasing grain protein, while the P and K requirements positively correlated with grain yield and protein content. Regression models were formulated to determine the nutrient requirements (MENR), enabling the prediction of N, P, and K requirements for leading cultivars with varying grain yields and protein contents. Implementing nutrient requirements based on MENR projections resulted in substantial reductions in fertilizer rates: 22.0 kg ha-1 N (10.7 %), 9.9 kg ha-1 P (20.2 %), and 8.1 kg ha-1 K (16.3 %). This translated to potential savings of 0.4 Mt. N, 0.23 Mt. P, and 0.17 Mt. K, consequently mitigating 5.5 Mt. CO2 greenhouse-gas emission and yielding an economic benefit of 0.8 billion US$ annually in China. These findings underscore the significance of considering grain yield and protein content in estimating nutrient requirements for fertilizer recommendations to realize high-yielding, high-protein wheat production, and minimize overfertilization and associated environmental risks.


Subject(s)
Edible Grain , Fertilizers , Nitrogen , Phosphorus , Potassium , Triticum , China , Nitrogen/analysis , Potassium/analysis , Potassium/metabolism , Phosphorus/analysis , Edible Grain/growth & development , Triticum/growth & development , Agriculture/methods , Nutrients/analysis
14.
Membranes (Basel) ; 14(6)2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38921508

ABSTRACT

A membrane condenser (MC) is a novel membrane separation technology that utilizes the hydrophobic nature of porous membranes to capture water vapor from humid gas. Factors such as temperature, pressure, flow rate, and gas composition entering the membrane condenser play a crucial role in water recovery efficiency. This study utilized hydrophobic polytetrafluoroethylene (PTFE) hollow fiber membranes to create multiple identical membrane modules. This research investigated the impact of temperature, flow rate, pressure on the intake side, gas flow on the cooling side, membrane area, and other variables on the performance of the membrane condenser process. This study compared water extraction efficiency under different conditions, focusing on feed flow temperature and sweeping flow. Results showed that at a temperature of 60 °C, the water recovery rate was 24.7%, while a sweep gas flow rate of 4 L/min resulted in a recovery rate of 22.7%. The efficiency of the membrane condenser decreased with higher feed flow rates but increased with larger membrane areas. A proportional relationship between inlet flow and membrane area was observed, suggesting an optimal range of 0.51-0.67 cm/s for both parameters. These findings offer valuable insights for the practical implementation of hydrophobic membrane-based membrane condenser technology.

15.
Conserv Physiol ; 12(1): coae040, 2024.
Article in English | MEDLINE | ID: mdl-38915852

ABSTRACT

The passive dissolution of anthropogenically produced CO2 into the ocean system is reducing ocean pH and changing a suite of chemical equilibria, with negative consequences for some marine organisms, in particular those that bear calcium carbonate shells. Although our monitoring of these chemical changes has improved, we have not developed effective tools to translate observations, which are typically of the pH and carbonate saturation state, into ecologically relevant predictions of biological risks. One potential solution is to develop bioindicators: biological variables with a clear relationship to environmental risk factors that can be used for assessment and management. Thecosomatous pteropods are a group of pelagic shelled marine gastropods, whose biological responses to CO2 have been suggested as potential bioindicators of ocean acidification owing to their sensitivity to acidification in both the laboratory and the natural environment. Using five CO2 exposure experiments, occurring across four seasons and running for up to 15 days, we describe a consistent relationship between saturation state, shell transparency and duration of exposure, as well as identify a suite of genes that could be used for biological monitoring with further study. We clarify variations in thecosome responses due to seasonality, resolving prior uncertainties and demonstrating the range of their phenotypic plasticity. These biomarkers of acidification stress can be implemented into ecosystem models and monitoring programmes in regions where pteropods are found, whilst the approach will serve as an example for other regions on how to bridge the gap between point-based chemical monitoring and biologically relevant assessments of ecosystem health.

16.
Front Bioeng Biotechnol ; 12: 1396892, 2024.
Article in English | MEDLINE | ID: mdl-38720877

ABSTRACT

Hydrogel is considered as a promising candidate for wound dressing due to its tissue-like flexibility, good mechanical properties and biocompatibility. However, traditional hydrogel dressings often fail to fulfill satisfied mechanical, antibacterial, and biocompatibility properties simultaneously, due to the insufficient intrinsic bactericidal efficacy and the addition of external antimicrobial agents. In this paper, hydroxyl-contained acrylamide monomers, N-Methylolacrylamide (NMA) and N-[Tris (hydroxymethyl)methyl] acrylamide (THMA), are employed to prepare a series of polyacrylamide hydrogel dressings xNMA-yTHMA, where x and y represent the mass fractions of NMA and THMA in the hydrogels. We have elucidated that the abundance of hydroxyl groups determines the antibacterial effect of the hydrogels. Particularly, hydrogel 35NMA-5THMA exhibits excellent mechanical properties, with high tensile strength of 259 kPa and large tensile strain of 1737%. Furthermore, the hydrogel dressing 35NMA-5THMA demonstrates remarkable inherent antibacterial without exogenous antimicrobial agents owing to the existence of abundant hydroxyl groups. Besides, hydrogel dressing 35NMA-5THMA possesses excellent biocompatibility, in view of marginal cytotoxicity, low hemolysis ratio, and negligible inflammatory response and organ toxicity to mice during treatment. Encouragingly, hydrogel 35NMA-5THMA drastically promote the healing of bacteria-infected wound in mice. This study has revealed the importance of polyhydroxyl in the antibacterial efficiency of hydrogels and provided a simplified strategy to design wound healing dressings with translational potential.

17.
Polymers (Basel) ; 16(9)2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38732663

ABSTRACT

The research used polyethersulfone (PES) as a membrane material, polyvinylpyrrolidone (PVP) k30 and polyethylene glycol 400 (PEG 400) as water-soluble additives, and dimethylacetamide (DMAc) as a solvent to prepare hollow-fiber ultrafiltration membranes through a nonsolvent-induced phase separation (NIPS) process. The hydrophilic nature of PVP-k30 and PEG caused them to accumulate on the membrane surface during phase separation. The morphology, chemical composition, surface charge, and pore size of the PES membranes were evaluated by SEM, FTIR, zeta potential, and dextran filtration experiments. The paper also investigated how different spinning solution compositions affected membrane morphology and performance. The separation efficiency of membranes with four different morphologies was tested in single-protein and double-protein mixed solutions. The protein separation effectiveness of the membrane was studied through molecular weight cutoff, zeta potential, and static protein adsorption tests. In addition, the operating pressure and pH value were adjusted to improve ultrafiltration process conditions. The PES membrane with an intact sponge-like structure showed the highest separation factor of 11, making it a prime candidate membrane for the separation of bovine serum albumin (BSA) and lysozyme (LYS). The membrane had a minimal static protein adsorption capacity of 48 mg/cm2 and had excellent anti-fouling properties. When pH = 4, the BSA retention rate was 93% and the LYS retention rate was 23%. Furthermore, it exhibited excellent stability over a pH range of 1-13, confirming its suitability for protein separation applications.

18.
Bioact Mater ; 38: 31-44, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38699238

ABSTRACT

Rapid development of checkpoint inhibitors has provided significant breakthroughs for cancer stem cell (CSC) therapy, while the therapeutic efficacy is restricted by hypoxia-mediated tumor immune evasion, especially hypoxia-induced CD47 overexpression in CSCs. Herein, we developed a genetically engineered CSC membrane-coated hollow manganese dioxide (hMnO2@gCMs) to elicit robust antitumor immunity by blocking CD47 and alleviating hypoxia to ultimately achieve the eradication of CSCs. The hMnO2 core effectively alleviated tumor hypoxia by inducing decomposition of tumor endogenous H2O2, thus suppressing the CSCs and reducing the expression of CD47. Cooperating with hypoxia relief-induced downregulation of CD47, the overexpressed SIRPα on gCM shell efficiently blocked the CD47-SIRPα "don't eat me" pathway, synergistically eliciting robust antitumor-mediated immune responses. In a B16F10-CSC bearing melanoma mouse model, the hMnO2@gCMs showed an enhanced therapeutic effect in eradicating CSCs and inhibiting tumor growth. Our work presents a simple, safe, and robust platform for CSC eradication and cancer immunotherapy.

19.
Sensors (Basel) ; 24(10)2024 May 08.
Article in English | MEDLINE | ID: mdl-38793842

ABSTRACT

Hyperspectral images (HSIs) contain subtle spectral details and rich spatial contextures of land cover that benefit from developments in spectral imaging and space technology. The classification of HSIs, which aims to allocate an optimal label for each pixel, has broad prospects in the field of remote sensing. However, due to the redundancy between bands and complex spatial structures, the effectiveness of the shallow spectral-spatial features extracted by traditional machine-learning-based methods tends to be unsatisfying. Over recent decades, various methods based on deep learning in the field of computer vision have been proposed to allow for the discrimination of spectral-spatial representations for classification. In this article, the crucial factors to discriminate spectral-spatial features are systematically summarized from the perspectives of feature extraction and feature optimization. For feature extraction, techniques to ensure the discrimination of spectral features, spatial features, and spectral-spatial features are illustrated based on the characteristics of hyperspectral data and the architecture of models. For feature optimization, techniques to adjust the feature distances between classes in the classification space are introduced in detail. Finally, the characteristics and limitations of these techniques and future challenges in facilitating the discrimination of features for HSI classification are also discussed further.

20.
Transl Oncol ; 45: 101982, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38718436

ABSTRACT

Immune checkpoints inhibitors are effective but it needs more precise biomarkers for patient selection. We explored the biological significance of LINC00862 in pan-cancer by bioinformatics. And we studied its regulatory mechanisms using chromatin immunoprecipitation and RNA immunoprecipitation assays etc. TCGA and single-cell sequencing data analysis indicated that LINC00862 was overexpressed in the majority of tumor and stromal cells, which was related with poor prognosis. LINC00862 expression was related with immune cell infiltration and immune checkpoints expression, and had a high predictive value for immunotherapy efficacy. Mechanistically, LINC00862 competitively bound to miR-29c-3p to unleash SIRT1's tumor-promoting function. SIRT1 inhibitor-EX527 were screened by virtual screening and verified by in vitro and vivo assays. Notably, acetyltransferase P300-mediated super-enhancer activity stimulated LINC00862 transcription. Collectively, LINC00862 could be a diagnostic and prognostic biomarker. LINC00862 could also be a predictive biomarker for immunotherapy efficacy. Super-enhancer activity is the driver for LINC00862 overexpression in cervical cancer and gastric cancer.

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