RESUMO
JOURNAL/nrgr/04.03/01300535-202508000-00031/figure1/v/2024-09-30T120553Z/r/image-tiff The protein connector enhancer of kinase suppressor of Ras 2 (CNKSR2), present in both the postsynaptic density and cytoplasm of neurons, is a scaffolding protein with several protein-binding domains. Variants of the CNKSR2 gene have been implicated in neurodevelopmental disorders, particularly intellectual disability, although the precise mechanism involved has not yet been fully understood. Research has demonstrated that CNKSR2 plays a role in facilitating the localization of postsynaptic density protein complexes to the membrane, thereby influencing synaptic signaling and the morphogenesis of dendritic spines. However, the function of CNKSR2 in the cytoplasm remains to be elucidated. In this study, we used immunoprecipitation and high-resolution liquid chromatography-mass spectrometry to identify the interactors of CNKSR2. Through a combination of bioinformatic analysis and cytological experiments, we found that the CNKSR2 interactors were significantly enriched in the proteome of the centrosome. We also showed that CNKSR2 interacted with the microtubule protein DYNC1H1 and with the centrosome marker CEP290. Subsequent colocalization analysis confirmed the centrosomal localization of CNKSR2. When we downregulated CNKSR2 expression in mouse neuroblastoma cells (Neuro 2A), we observed significant changes in the expression of numerous centrosomal genes. This manipulation also affected centrosome-related functions, including cell size and shape, cell proliferation, and motility. Furthermore, we found that CNKSR2 interactors were highly enriched in de novo variants associated with intellectual disability and autism spectrum disorder. Our findings establish a connection between CNKSR2 and the centrosome, and offer new insights into the underlying mechanisms of neurodevelopmental disorders.
RESUMO
T-bet and Eomes, both T-box transcription factors, have been extensively studied for their critical roles in the differentiation and functional maintenance of various immune cells. In this review, we provide a focused overview of their contributions to the transcriptional activation and differentiation, development, and terminal maturation of natural killer cells and innate lymphoid cell 1 cells. Furthermore, the interplay between T-bet and Eomes in regulating NK cell function, and its subsequent implications for immune responses against infections and tumors, is thoroughly examined. The review explores the ramifications of dysregulated transcription factor expression, examining its impact on homeostatic balance and its role in a spectrum of disease models. Expression variances among distinct NK cell subsets resident in different tissues are highlighted to underscore the complexity of their biological roles. Collectively, this work aims to expand the current understanding of NK cell biology, thereby paving the way for innovative approaches in the realm of NK cell-based immunotherapies.
RESUMO
Chronic diseases, which require long-term continuous care due to the long clinical courses, may cause severe harm to the psychological well-being of a large population in the U.S. Providing convenient and affordable access to healthcare, online patient-provider communication (OPPC) is considered a potentially effective means in safeguarding psychological well-being among patients with chronic diseases. However, what underlying mechanism OPPC helps patients deal with psychological issues is largely unknown in the context of chronic diseases. Thus, drawing on the health communication pathway model, this study seeks to address the gap by investigating the psychological and behavioral mechanism of how OPPC alleviates psychological distress among patients with chronic diseases. Analyzing secondary data derived from the Health Information National Trends Survey (HINTS 5, Cycle 3, N = 879), this study reveals that OPPC can elicit perceptions of patient-centered communication (PCC) and facilitate patients to take adaptive coping strategies, including problem-oriented and emotion-oriented coping, thus alleviating psychological distress among patients with chronic diseases. However, only emotion-oriented coping in this process significantly reduces psychological distress. On this basis, this study advances the understanding of the therapeutic effect of OPPC among patients with chronic diseases and extends the health communication pathway model by examining the role of patient-provider communication in facilitating adaptive coping strategies.
RESUMO
BACKGROUND: Third-generation sequencing (TGS) based on long-read technology has been gradually used in identifying thalassemia and hemoglobin (Hb) variants. The aim of the present study was to explore genotype varieties of thalassemia and Hb variants in Quanzhou region of Southeast China by TGS. METHODS: Included in this study were 6,174 subjects with thalassemia traits from Quanzhou region of Southeast China. All of them underwent common thalassemia gene testing using the DNA reverse dot-blot hybridization technology. Subjects who were suspected as rare thalassemia carriers were further subjected to TGS to identify rare or novel α- and ß-globin gene variants, and the results were verified by Sanger sequencing and/or gap PCR. RESULTS: Of the 6,174 included subjects, 2,390 (38.71%) were identified as α- and ß-globin gene mutation carriers, including 40 carrying rare or novel α- and ß-thalassemia mutations. The αCD30(-GAG)α and Hb Lepore-Boston-Washington were first reported in Fujian province Southeast China. Moreover, the ßCD15(TGG> TAG), ßIVS-II-761, ß0-Filipino(~ 45 kb deletion), and Hb Lepore-Quanzhou were first identified in the Chinese population. In addition, 35 cases of Hb variants were detected, the rare Hb variants of Hb Jilin and Hb Beijing were first reported in Fujian province of China. Among them, one case with compound αααanti3.7 and Hb G-Honolulu variants was identified in this study. CONCLUSION: Our findings may provide valuable data for enriching the spectrum of thalassemia and highlight the clinical application value of TGS-based α- and ß-globin genetic testing.
Assuntos
alfa-Globinas , Globinas beta , Humanos , Globinas beta/genética , alfa-Globinas/genética , China , Feminino , Masculino , Adulto , Sequenciamento de Nucleotídeos em Larga Escala , Mutação , Adolescente , Criança , Talassemia/genética , Adulto Jovem , Talassemia beta/genética , Genótipo , Povo Asiático/genética , Pessoa de Meia-Idade , Talassemia alfa/genética , População do Leste AsiáticoRESUMO
BACKGROUND: Intermediate cells are present in the early stages of human prostate development and adenocarcinoma. While primary cells isolated from benign human prostate tissues or tumors exhibit an intermediate phenotype in vitro, they cannot form tumors in vivo unless genetically modified. It is unclear about the stem cell properties and tumorigenicity of intermediate cells. METHODS: We developed a customized medium to culture primary human intermediate prostate cells, which were transplanted into male immunodeficient NCG mice to examine tumorigenicity in vivo. We treated the cells with different concentrations of dihydrotestosterone (DHT) and enzalutamide in vitro and surgically castrated the mice after cell transplantation in vivo. Immunostaining, qRT-PCR, RNA sequencing, and western blotting were performed to characterize the cells in tissues and 2D and 3D cultures. RESULTS: We found intermediate cells expressing AR+PSA+CK8+CK5+ in the luminal compartment of human prostate adenocarcinoma by immunostaining. We cultured the primary intermediate cells in vitro, which expressed luminal (AR+PSA+CK8+CK18+), basal (CK5+P63+), intermediate (IVL+), and stem cell (CK4+CK13+PSCA+SOX2+) markers. These cells resisted castration in vitro by upregulating the expression of AR, PSA, and proliferation markers KI67 and PCNA. The intermediate cells had high tumorigenicity in vivo, forming tumors in immunodeficient NCG mice in a month without any genetic modification or co-transplantation with embryonic urogenital sinus mesenchyme (UGSM) cells. We named these cells human castration-resistant intermediate prostate cancer stem cells or CriPCSCs and defined the xenograft model as patient primary cell-derived xenograft (PrDX). Human CriPCSCs resisted castration in vitro and in vivo by upregulating AR expression. Furthermore, human CriPCSCs differentiated into amplifying adenocarcinoma cells of luminal phenotype in PrDX tumors in vivo, which can dedifferentiate into CriPCSCs in vitro. CONCLUSIONS: Our study identified and established methods for culturing human CriPCSCs, which had high tumorigenicity in vivo without any genetic modification or UGSM co-transplantation. Human CriPCSCs differentiated into amplifying adenocarcinoma cells of luminal phenotype in the fast-growing tumors in vivo, which hold the potential to dedifferentiate into intermediate stem cells. These cells resisted castration by upregulating AR expression. The human CriPCSC and PrDX methods hold significant potential for advancing prostate cancer research and precision medicine.
Assuntos
Adenocarcinoma , Células-Tronco Neoplásicas , Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/patologia , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/genética , Animais , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Camundongos , Adenocarcinoma/patologia , Adenocarcinoma/metabolismo , Adenocarcinoma/genética , Nitrilas/farmacologia , Feniltioidantoína/farmacologiaRESUMO
N7-Methylguanosine (m7G) is important RNA modification at internal and the cap structure of five terminal end of message RNA. It is essential for RNA stability of RNA, the efficiency of translation, and various intracellular RNA processing pathways. Given the significance of the m7G modification, numerous studies have been conducted to predict m7G sites. To further elucidate the regulatory mechanisms surrounding m7G, we introduce a novel bioinformatics framework, m7GRegpred, designed to forecast the targets of the m7G methyltransferases METTL1 and WDR4, and m7G readers QKI5, QKI6, and QKI7 for the first time. We integrated different features to build predictors, with AUROC scores of 0.856, 0.857, 0.780, 0.776, 0.818 for METTL1, WDR4, QKI5, QKI6, and QKI7, respectively. In addition, the effect of window lengths and algorism were systemically evaluated in this work. The finial model was summarized in a user-friendly webserver: http://modinfor.com/m7GRegpred/. Our research indicates that the substrates of m7G regulators can be identified and may potentially advance the study of m7G regulators under unique conditions.
RESUMO
Aqueous zinc-ion batteries are attracting extensive attention due to the long-term service life and credible safety as well as the superior price performance between the low cost of manufacture and high energy density. The fabrication of inexpensive, high-performance flexible solid-state zinc-ion batteries, thus, are urgently need for the blooming wearable electronics. Herein, as a proof-of-concept study of waste into wealth, cellulose flakes derived from waste pomelo peel are utilized as the substrate for electrodes and hydrogel electrolytes into a flexible rocking-chair zinc-ion battery. The unique sandwich-type structure holding the flake-like cellulose substrate and linear carbon nanotubes endows the flexible cathode and anode with fast ion and electron transportation. The obtained cellulose-based hydrogel electrolytes on account of special affinity with aqueous ZnSO4 electrolyte output an excellent ionic conductivity. The assembled flexible rocking-chair zinc-ion battery benefitting from the synergistic effect of sandwich-type electrodes and cellulose-based hydrogel electrolytes demonstrates outstanding electrochemical performance and mechanical properties. This work not only puts up an effective roadmap for flexible battery devices, but also reveals the great potential of waste biomass materials in energy storage applications.
RESUMO
A new species of the firmoss from China, Huperziacrassifolia sp. nov., is described and illustrated based on morphological characters and molecular evidence. The new species resembles species associated with the H.javanica complex, in particular H.javanica based on leaf shape and serrations, but can be easily distinguished by elliptic lanceolate and thick coriaceous leaves, well differentiated seasonal constriction zones, and reflexed leaf margins when get dried. Phylogenomic reconstruction using whole chloroplast genome sequences recovered H.crassifolia as sister to H.sutchueniana and only distantly related to morphological similar species H.javanica, H.nanlingensis, and H.serrata. The genome size 2C = 17.2 pg indicated the new species to be a tetraploid, whereas diploid H.javanica had a genome size of 8.7 pg. Morphological characters, distribution, and conservation status of the new species are also presented.
RESUMO
BACKGROUND: Intracranial artery stenosis (ICAS) and cerebral small vessel disease (CSVD) are associated with a heavy socioeconomic burden; however, their longitudinal changes remain controversial. METHODS: We conducted a longitudinal analysis on 756 participants of Shunyi Cohort who underwent both baseline and follow-up brain magnetic resonance imaging (MRI) and MR angiography in order to investigate the risk factors for ICAS and CSVD progression in community population. Incident ICAS was defined as new stenosis occurring in at least one artery or increased severity of the original artery stenosis. CSVD markers included lacunes, cerebral microbleeds (CMB), and white matter hyperintensities (WMH). RESULTS: After 5.58 ± 0.49 years of follow-up, 8.5% of the 756 participants (53.7 ± 8.0 years old, 65.1% women) had incident ICAS. Body mass index (BMI) (OR = 1.09, 95% CI = 1.01-1.17, p = 0.035) and diabetes mellitus (OR = 2.67, 95% CI = 1.44-4.93, p = 0.002) were independent risk factors for incident ICAS. Hypertension was an independent risk factor for incident lacunes (OR = 2.12, 95% CI = 1.20-3.77, p = 0.010) and CMB (OR = 2.32, 95% CI = 1.22-4.41, p = 0.011), while WMH progression was primarily affected by BMI (ß = 0.108, SE = 0.006, p = 0.002). A higher LDL cholesterol level was found to independently protect against WMH progression (ß = -0.076, SE = 0.027, p = 0.019). CONCLUSIONS: Modifiable risk factor profiles exhibit different in patients with ICAS and CSVD progression. Controlling BMI and diabetes mellitus may help to prevent incident ICAS, and antihypertensive therapy may conduce to mitigate lacunes and CMB progression. LDL cholesterol may play an inverse role in large arteries and small vessels.
Assuntos
Doenças de Pequenos Vasos Cerebrais , Progressão da Doença , Humanos , Masculino , Doenças de Pequenos Vasos Cerebrais/epidemiologia , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Feminino , Pessoa de Meia-Idade , Fatores de Risco , Estudos Longitudinais , Imageamento por Ressonância Magnética/métodos , Constrição Patológica/epidemiologia , Adulto , Idoso , Hipertensão/epidemiologia , Hipertensão/complicaçõesRESUMO
INTRODUCTION: This study combined the bioinformatics and in vitro experiment-related technologies to analyze the impact of steroid 5 alpha-reductase 3 (SRD5A3) on the prognosis and immune microenvironment of Liver Hepatocellular Carcinoma (LIHC). METHOD: Gene expression and clinical data were obtained from public databases. The prognosis was evaluated using survival, multifactor Cox, enrichment, and mutation analyses. This was then verified through in vitro experiments. RESULTS: The expression level of SRD5A3 in LIHC tissues was significantly higher than that in the adjacent tissues. Kaplan-Meier survival analysis showed that high SRD5A3 expression was associated with poor overall survival (OS) and short progression-free survival in patients with LIHC. Multivariate Cox regression analysis revealed that positive SRD5A3 expression was an independent risk factor for OS in patients with LIHC. Expression of SRD5A3 was negatively correlated with immune cell infiltration of CD4+ T, CD8+ T, and B cells. GO and KEGG enrichment analyses showed that SRD5A3 was significantly enriched in signaling- and tumor metastasis-related pathways. Nomogram and calibration curve showed that the predicted performance of the model was consistent with the actual results. In vitro results confirmed that SRD5A3 knockdown inhibited the migration, invasion, and proliferation of LIHC cells. CONCLUSIONS: SRD5A3 is actively expressed in LIHC, and positive expression of SRD5A3 is an independent risk factor for different prognoses in patients with LIHC. SRD5A3 can promote the proliferation, migration, and invasion of liver cancer cells and is related to short immune infiltration in patients with LIHC.
High SRD5A3 expression is significantly associated with poor prognosis in patients with LIHC and may help assess tumor progression.Highly expressed SRD5A3 promotes migration, invasion, and proliferation of liver cancer cells.SRD5A3 expression is related to the degree of tumor immune cell infiltration.
Assuntos
3-Oxo-5-alfa-Esteroide 4-Desidrogenase , Carcinoma Hepatocelular , Neoplasias Hepáticas , Microambiente Tumoral , Humanos , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Microambiente Tumoral/imunologia , 3-Oxo-5-alfa-Esteroide 4-Desidrogenase/genética , 3-Oxo-5-alfa-Esteroide 4-Desidrogenase/metabolismo , Prognóstico , Masculino , Feminino , Pessoa de Meia-Idade , Regulação Neoplásica da Expressão Gênica , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Estimativa de Kaplan-Meier , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Proliferação de Células/genética , Linhagem Celular TumoralRESUMO
Radioactive nuclides and highly toxic organophosphates are typical deadly threats. Materials with the function of radioactive substances adsorption and organophosphates degradation provide double protection. Herein, dual-functional polyamide (PA)/polyethyleneimine (PEI)@Zr-MOF fiber composite membranes, fabricated by in-situ solvothermal growth of Zr-MOF on PA/PEI electrospun fiber membranes, are designed for protection against two typical model compounds of iodine and dimethyl 4-nitrophenyl phosphate (DMNP). Benefiting from the unique core-sheath structure composed of inner nitrogen-rich fibers and outer porous Zr-MOF, the composite membranes rapidly enrich iodine through abundant active sites of the outer sheath and form complexes with the amine of inner PEI, exhibiting a highly competitive adsorption capacity of 609 mg g-1. Moreover, it can adsorb and degrade DMNP with the synergy of PEI component and Zr-MOF, achieving an 80 % removal of DMNP within 7 min without any additional co-catalyst. This work provides a feasible strategy to fabricate dual-functional materials that protect against radioactive and organophosphorus contaminants.
RESUMO
Purple bacteria possess two ring-shaped protein complexes, light-harvesting 1 (LH1) and 2 (LH2), both of which function as antennas for solar energy utilization for photosynthesis but exhibit distinct absorption properties. The two antennas have differing amounts of bacteriochlorophyll (BChl) a; however, their significance in spectral tuning remains elusive. Here, we report a high-precision evaluation of the physicochemical factors contributing to the variation in absorption maxima between LH1 and LH2, namely, BChl a structural distortion, protein electrostatic interaction, excitonic coupling, and charge transfer (CT) effects, as derived from detailed spectral calculations using an extended version of the exciton model, in the model purple bacterium Rhodospirillum rubrum. Spectral analysis confirmed that the electronic structure of the excited state in LH1 extended to the BChl a 16-mer. Further analysis revealed that the LH1-specific redshift (â¼61% in energy) is predominantly accounted for by the CT effect resulting from the closer inter-BChl distance in LH1 than in LH2. Our analysis explains how LH1 and LH2, both with chemically identical BChl a chromophores, use distinct physicochemical effects to achieve a progressive redshift from LH2 to LH1, ensuring efficient energy transfer to the reaction center special pair.
RESUMO
Respiratory syncytial virus (RSV)-induced viral pneumonia in children is common worldwide. Its high occurrence and lack of an effective vaccine make it a leading cause of death in children. Severe RSV infection can trigger uncontrolled inflammatory responses in patients, so the development of small molecule drugs with the dual function of "direct antivirus" and "inflammatory response regulation" is welcome. Resveratrol (Res) has been reported to have antiviral and anti-inflammatory pharmacological effects, but its application is limited because of its poor water solubility and oral bioavailability. Based on small-molecule nanotechnology, we developed a sonication-assisted self-assembly method for preparing insoluble Res into highly soluble resveratrol nanoparticles (Res NPs). The obtained Res NPs exhibited a higher water solubility and a faster dissolution rate, which was more conducive to the effectiveness of Res in addressing RSV-induced viral pneumonia. In vitro studies had shown that Res NPs played an antiviral role by inhibiting RSV replication and reducing the production of pro-inflammatory cytokines. Nebulized inhalation administration of Res NPs prolonged the drug's residence time in the lungs, which appears to increase the accumulation and effectiveness of Res NPs. Additionally, in vivo studies had demonstrated significant benefits of Res NPs in inhibiting RSV viral load and improving the pulmonary microenvironment in RSV-infected mice. Both antiviral and anti-inflammatory experiments had confirmed that the pharmacological activity of Res NPs is superior to that of Res. This suggested that nanosizing Res was an effective way to enhance the original pharmacological activity of Res and also offered a new formulation strategy for treating viral pneumonia.
Assuntos
Anti-Inflamatórios , Antivirais , Nanopartículas , Infecções por Vírus Respiratório Sincicial , Resveratrol , Sonicação , Resveratrol/farmacologia , Resveratrol/química , Resveratrol/administração & dosagem , Nanopartículas/química , Animais , Antivirais/química , Antivirais/farmacologia , Antivirais/administração & dosagem , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Infecções por Vírus Respiratório Sincicial/virologia , Camundongos , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/administração & dosagem , Humanos , Camundongos Endogâmicos BALB C , Vírus Sinciciais Respiratórios/efeitos dos fármacos , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/virologia , Feminino , Replicação Viral/efeitos dos fármacos , Pulmão/virologia , Pulmão/efeitos dos fármacos , Pulmão/patologiaRESUMO
Corynebacterium glutamicum is a major workhorse in the industrial production of branched-chain amino acids (BCAAs). The acetohydroxyacid synthase (AHAS) encoded by ilvBN is a key enzyme in the biosynthesis of BCAAs. Enhancing AHAS expression is essential for engineering BCAA producers. However, at present, the available studies only used limited promoters to regulate AHAS expression, which is insufficient for achieving efficient regulation. Herein, we first employed a previously developed reporter system to screen out a strong constitutive promoter PgpmA* from six candidate promoters for expressing ilvBN. PgpmA* showcased the expression strength 23.3-fold that of the native promoter PilvBN. Moreover, three synthetic RBS libraries based on the promoter PgpmA* were constructed and evaluated by plate fluorescence imaging. The results revealed that "R(9)N(6)" was the best mutant library. A total of 36 RBS mutants with enhanced strength were further screened by evaluation in 96-deep-well plates, and the highest strength reached up to 62.3-fold that of PilvBN. Finally, the promoter PgpmA* was combined with three RBS mutants (WT, RBS18, and RBS36) to fine-tune the expression of ilvBNS155F for L-valine biosynthesis, respectively. Increased expression strength led to enhanced L-valine production, with titers of 1.17, 1.38, and 2.29 g/L, respectively. The combination of RBS18 strain with the further overexpression of ilvC produced 7.57 g/L L-valine. The regulatory elements obtained in this study can be utilized to modulate AHAS expression for BCAA production in C. glutamicum. Additionally, this strategy can guide the efficient expression regulation of other key enzymes.
Assuntos
Acetolactato Sintase , Aminoácidos de Cadeia Ramificada , Corynebacterium glutamicum , Regulação Bacteriana da Expressão Gênica , Regiões Promotoras Genéticas , Corynebacterium glutamicum/genética , Corynebacterium glutamicum/metabolismo , Aminoácidos de Cadeia Ramificada/biossíntese , Aminoácidos de Cadeia Ramificada/metabolismo , Aminoácidos de Cadeia Ramificada/genética , Acetolactato Sintase/genética , Acetolactato Sintase/metabolismo , Engenharia Metabólica/métodos , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismoRESUMO
Titanium dioxide (TiO2) is widely employed in the catalytic degradation of wastewater, owing to its robust stability, superior photocatalytic efficiency, and cost-effectiveness. Nonetheless, isolating the fine particulate photocatalysts from the solution post-reaction poses a significant challenge in practical photocatalytic processes. Furthermore, these particles have a tendency to agglomerate into larger clusters, which diminishes their stability. To address this issue, the present study has developed Al2O3-SiO2-TiO2 composite semiconductor porous ceramics and has systematically explored the influence of Al2O3 and SiO2 on the structure and properties of TiO2 porous ceramics. The findings reveal that the incorporation of Al2O3 augments the open porosity of the ceramics and inhibits the aggregation of TiO2, thereby increasing the catalytic site and improving the light absorption capacity. On the other hand, the addition of SiO2 enhances the bending strength of the ceramics and inhibits the conversion of anatase to rutile, thereby further enhancing its photocatalytic activity. Consequently, at an optimal composition of 55 wt.% Al2O3, 40 wt.% TiO2, and 5 wt.% SiO2, the resulting porous ceramics exhibit a methylene blue removal rate of 91.50%, and even after undergoing five cycles of testing, their catalytic efficiency remains approximately 83.82%. These outcomes underscore the exceptional photocatalytic degradation efficiency, recyclability, and reusability of the Al2O3-SiO2-TiO2 porous ceramics, suggesting their substantial potential for application in the treatment of dye wastewater, especially for the removal of methylene blue.
RESUMO
The microsatellite stable (MSS) colon cancer (CC) has long been considered resistant to immunotherapy. Cuproptosis, as a novel form of cell death, may interact with tumor immunity. This project focused on the impact of cuproptosis on the cytotoxicity of CD8+T in MSS CC, aiming to provide effective clues for improving the treatment strategy of MSS CC. The study developed an MSS CC cuproptosis model using 50 nM elesclomol and 1 µM CuCl2. Cuproptotic SW480 cells were directly co-cultured with CD8+ T cells. Cuproptosis levels were assessed via intracellular copper ion detection, Western blot, and confocal laser scanning microscopy. CCK-8, Hochest/PI staining, CFSE cell proliferation assay, LDH cytotoxicity detection, and ELISA were used to evaluate CD8+ T cell immune activity and cytotoxicity. Transcriptome sequencing and bioinformatics analysis identified regulated signals in cuproptotic SW480 cells. A rescue experiment utilized a WNT pathway activator (BML-284). PD-L1 expression in cells/membranes was analyzed using qRT-PCR, Western blot, and flow cytometry. NSG mice were immunoreconstituted, and the effects of cuproptosis on immune infiltration and cancer progression in MSS CC mice were assessed using ELISA and immunohistochemistry (IHC). Treatment with 50 nM elesclomol and 1 µM CuCl2 significantly increased cuproptosis in SW480 cells. Co-culture with CD8+ T cells enhanced their cytotoxicity. Sequencing revealed cuproptosis-mediated modulation of immune and inflammatory pathways, including WNT signaling. Rescue experiments showed downregulation of WNT signaling in cuproptotic SW480 cells. Indirectly, CD8+ T cell immune function was enhanced by reducing PD-L1 expression. In mice, cuproptosis resulted in increased infiltration of CD8+ T cells in tumor tissue, leading to delayed cancer progression compared to the control group. Cuproptosis in MSS CC cells enhances the cytotoxicity of CD8+ T cells, which may be achieved through downregulation of the WNT signaling pathway and decreased expression of PD-L1. In the future, drugs that can induce cuproptosis may be a promising approach to improve MSS CC immunotherapy.
RESUMO
Textiles that can repeatedly change color in the presence of external stimuli have attracted great interest. Effectively designing to produce such functional textiles is essential, yet there remain challenges like producing stable coloration, rapid response, and reverse color changing. Here, the preparation of a magnetic field response (MFR) textile with a fast magnetic field response, brilliant structural coloration, and mechanical robustness is reported. The MFR textile is knitted by incorporating magnetic particles' ethylene glycol (EG) suspension within polydimethylsiloxane (PDMS)-based fibers. A surface modification strategy is designed to prevent EG from seeping out along the PDMS polymer chains. A PDMS fiber is encapsulated in waterborne polyurethane, and a polydopamine joint layer is used. The MFR textile demonstrates magnetic field-triggered structural colors, and the breaking strength and elongation at break of each composite fiber are improved. In addition, multishaped patterns can be printed on the MFR textile with the help of the photo etching technology, which enhances the applications of the new functional textiles.
RESUMO
Pyrroquinoline quinone (PQQ) is one of the important coenzymes in living organisms. In acetic acid bacteria (AAB) it plays a crucial role in alcohol respiratory chain, as a coenzyme of alcohol dehydrogenase. In this work, the PQQ biosynthetic genes were overexpressed in Acetobacter pasteurianus CGMCC 3089 to improve the fermentation performance. The result shows that the intracellular and extracellular PQQ contents in the recombinant strain A. pasteurianus (pBBR1-p264-pqq) were 152.53% and 141.08% higher than those of the control A. pasteurianus (pBBR1-p264), respectively. The catalytic activity of alcohol dehydrogenase and aldehyde dehydrogenase increased by 52.92% and 67.04%, respectively. The results indicated that the energy charge and intracellular ATP were also improved in the recombinant strain. The acetic acid fermentation was carried out using a 5 L self-aspirating fermenter, and the acetic acid production rate of the recombinant strain was 23.20% higher compared with the control. Furthermore, the relationship between the PQQ and acetic acid tolerance of cells was analyzed. The biomass of recombinant strain was 180.2%, 44.3%, and 38.6% higher than those of control under 2%, 3%, and 4% acetic acid stress, respectively. After treated with 6% acetic acid for 40 min, the survival rate of the recombinant strain was increased by 76.20% compared with the control. Those result demonstrated that overexpression of PQQ biosynthetic genes increased the content of PQQ, therefore improving the acetic acid fermentation and the cell tolerance against acetic acid by improving the alcohol respiratory chain and energy metabolism.
RESUMO
Detecting a microwave signal that is emitted or reflected by distant targets is a powerful tool in fundamental science and industrial technology. Solid-state spins provide an opportunity to realize quantum-enhanced remote sensing under ambient conditions. However, the weak interaction between the free-space signal and atomic size sensor limits the sensitivity. This hinders the realization of practical quantum remote sensing. Here, we demonstrate active microwave remote sensing with a diamond-based hybrid quantum receiver by combining electromagnetic field localization at nanoscale with quantum spin manipulation. A method of differential spin refocusing (DSR) is developed to overcome the challenge of reducing the impact of inhomogeneities in spin-signal interaction, while the strength of interaction is enhanced by more than 3 orders with nanostructure. It improves the coherent interaction time of quantum receiver by 30-fold, substantially enhancing the sensitivity and stability. By detecting the reflected microwave with picotesla sensitivity, diamond remote sensing monitors the real-time status of a centimeter-sized target at 2 m distance. Our method is general to various solid-state spins. The results will expand the applications of solid-state spin quantum sensors in areas ranging from medical imaging to resource survey.