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Gastric cancer (GC) is a malignancy with a relatively high mortality rate. This study aimed to ascertain the prognostic significance of long non-coding RNA (lncRNA) AC010457.1 in GC and elucidate its role in disease progression. The Cancer Genome Atlas (TCGA) database was used to screen the prognosis-associated differentially expressed lncRNAs in GC patients. Kaplan-Meier curves, univariate and multivariate Cox regression analyses were applied to assess the prognostic significance of AC010457.1. In vitro and in vivo functional assays were performed to evaluate the effects of AC010457.1 on cellular proliferation and metastasis. Mechanistic investigations, including Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, Western blotting (WB), Immunofluorescence (IF), and Immunohistochemistry (IHC), were used to explore the signaling pathways activated by AC010457.1. We demonstrated that AC010457.1 was abnormally upregulated in GC tissues, and that this aberrant upregulation was associated with a poor prognosis for GC patients. The functional experiments proved that the downregulated of AC010457.1 hindered GC cell proliferation, migration, and invasive potential. Furthermore, KEGG analysis revealed a significant association between AC010457.1 and the PI3K/AKT signaling pathway, which was further corroborated by WB analysis. Rescue experiments provided additional confirmation that AC010457.1 regulated PI3K/AKT promote GC proliferation, migration, and epithelial-mesenchymal transition (EMT). Collectively, our findings suggest that AC010457.1 overexpression serves as a distinct prognostic risk factor in GC and may represent a promising therapeutic target for the treatment of this malignancy.
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BACKGROUND: The SCY1-like (SCYL) family has been reported to be closely related to cancer metastasis, but it has not been reported in gastric cancer (GC), and its specific mechanism is not clear. METHODS: We utilized databases like Deepmap, TCGA, and GEO to identify SCYL1's role in GC. Clinical samples were analyzed for SCYL1 expression and its correlation with patient prognosis. In vitro and in vivo experiments were conducted to assess SCYL1's function in GC cell migration, invasion, and autophagy. RESULTS: SCYL1 showed an increased expression in GC tissues, which correlated with a negative prognosis. In vitro experiments demonstrated that SCYL1 promotes GC cell migration and invasion and inhibits autophagy. GSEA indicated an inverse relationship between SCYL1 and autophagy, while a direct relationship was observed with the mTORC1 signaling pathway. Knockdown of SCYL1 enhanced autophagy, while activation of mTORC1 reversed this effect. CONCLUSIONS: SCYL1 is a significant contributor to GC progression, promoting metastasis by activating the mTORC1 signaling pathway and inhibiting autophagy. These findings suggest SCYL1 as a potential therapeutic target for GC treatment.
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Diana Mecanicista del Complejo 1 de la Rapamicina , Transducción de Señal , Neoplasias Gástricas , Animales , Femenino , Humanos , Masculino , Ratones , Autofagia , Línea Celular Tumoral , Movimiento Celular , Regulación Neoplásica de la Expresión Génica , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Ratones Endogámicos BALB C , Ratones Desnudos , Metástasis de la Neoplasia , Pronóstico , Neoplasias Gástricas/patología , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/genéticaRESUMEN
The contents of 57 ginsenosides were measured in American ginseng roots collected from a single population grown in Jilin. Ginsenoside contents and compositions varied significantly among the population. The most abundant ginsenoside within the American ginseng root and by population was either Rg1 or Re, followed by Rb1, mal-Rb1, Rd, Rc, pseudoginsenoside F11, Ro, and gypenoside XVII. According to the relative contents of Rg1 and Re, the population was grouped into two chemotypes, and there were significant differences in ginsenoside profiles between them. The contents of protopanaxadiol-type ginsenosides were relatively stable. The rate-limiting enzymes of malonyl ginsenosides biosynthesis were located in front of their corresponding neutral ginsenosides. The regulatory sites of the oleanolic acid-type ginsenosides biosynthetic pathway were in front of the ß-amyrin.
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The potential of macrophage-mediated phagocytosis as a cancer treatment is promising. Blocking the CD47-SIRPα interaction with a CD47-specific antibody significantly enhances macrophage phagocytosis. However, concerns regarding their toxicity to nontumor cells remain substantial. Here, we engineered chimeric antigen receptor macrophages (CAR-Ms) by fusing a humanized single-chain variable fragment with FcγRIIa and integrating short hairpin RNA to silence SIRPα, thereby disrupting the CD47-SIRPα signaling pathway. These modified CAR-shSIRPα-M cells exhibited an M1-like phenotype, superior phagocytic function, substantial cytotoxic effects on HER2-positive tumor cells, and the ability to eliminate patient-derived organoids. In vivo, CAR-M cells significantly inhibited tumor growth and prolonged survival in tumor-bearing mice. Notably, CAR-shSIRPα-M cells enhanced cytotoxic T-cell infiltration into tumors, thereby enhancing the antitumor response in both the humanized immune system mouse model and immunocompetent mice. Mechanistically, SIRPα inhibition activated inflammatory pathways and the cGAS-STING signaling cascade in CAR-M cells, leading to increased production of proinflammatory cytokines, reactive oxygen species, and nitric oxide, thereby enhancing their antitumor effects. These findings underscore the potential of SIRPα inhibition as a novel strategy to increase the antitumor efficacy of CAR-M cells in cancer immunotherapy, particularly against solid tumors.
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As one of the most important economic traits for domestic animal husbandry, skeletal muscle is regulated by an intricate molecular network. Adenosine deaminase acting on RNA (ADAR1) involves various physiological processes and diseases, such as innate immunity and the development of lung adenocarcinoma, breast cancer, gastric cancer, etc. However, its role in skeletal muscle growth requires further clarification. Here, we explored the functions of ADAR1 in the myogenic process of goat skeletal muscle satellite cells (MuSCs). The ADAR1 transcripts were noticeably enriched in goat visceral tissues compared to skeletal muscle. Additionally, its levels in slow oxidative muscles like the psoas major and minor muscles were higher than in the fast oxidative glycolytic and fast glycolytic muscles. Among the two common isoforms from ADAR1, p110 is more abundant than p150. Moreover, overexpressing ADAR1 enhanced the proliferation and myogenic differentiation of MuSCs. The mRNA-seq performed on MuSCs' knockdown of ADAR1 obtained 146 differentially expressed genes (DEGs), 87 upregulated and 59 downregulated. These DEGs were concentrated in muscle development and process pathways, such as the MAPK and cAMP signaling pathways. Furthermore, many DEGs as the key nodes defined by protein-protein interaction networks (PPI), including STAT3, MYH3/8, TGFß2, and ACTN4, were closely related to the myogenic process. Finally, RNA immunoprecipitation combined with qPCR (RIP-qPCR) showed that ADAR1 binds to PAX7 and MyoD mRNA. This study indicates that ADAR1 promotes the myogenic development of goat MuSCs, which provides a useful scientific reference for further exploring the ADAR1-related regulatory networks underlying mammal skeletal muscle growth.
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Adenosina Desaminasa , Diferenciación Celular , Proliferación Celular , Cabras , Desarrollo de Músculos , Células Satélite del Músculo Esquelético , Animales , Células Satélite del Músculo Esquelético/metabolismo , Adenosina Desaminasa/metabolismo , Adenosina Desaminasa/genética , Diferenciación Celular/genética , Desarrollo de Músculos/genéticaRESUMEN
Altering the physical structure and chemical property of copper, i.e., particle size, surface morphology, composition or crystal facet, has been demonstrated to be effective in steering the selectivity of products in electrochemical reduction of carbon dioxide. However, these modifications generally result in the change of active surface area, leading to differences in the geometric current density and local pH, which are also demonstrated to be the key factors for observed selectivity change. In this work, we deconvolute the effect of mass transport and local pH from the effect of crystal facet by investigating five copper-based catalysts with identical roughness factors for electrochemical reduction of carbon dioxide in an H-cell. Interestingly, CuO-derived catalyst stands out as the best catalyst for C-C coupling. At -1.07 V vs. RHE, the faradaic efficiency of C2+ product reaches 44.3%, with a partial current density of -10.8 mA cm-2. Electrochemical adsorption of *OH reveals that the C2+ product selectivity of derived-copper catalysts correlates positively with the ratio of Cu(100)/Cu(110) of five catalysts. Additionally, in situ Raman spectroscopy reveals that the percentage of low-frequency band linear CO (LFB-CO), which is attributed to the adsorbed *CO on Cu(100) facet, increases with the C-C coupling efficiency.
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Background and Objectives: Systemic lupus erythematosus (SLE) is distinguished by dysregulated immune system activity, resulting in a spectrum of clinical manifestations, with lupus nephritis being particularly prominent. This study endeavors to discern novel targets as potential therapeutic markers for this condition. Methods: Weighted correlation network analysis (WGCNA) was used to construct the network and select the key hub genes in the co-expression module based on the gene expression dataset GSE81622. Subsequently, functional enrichment and pathway analysis were performed for SLE and lupus nephritis. In addition, also identify genes and differences in SLE with lupus nephritis and methylation site. Finally, qRT-PCR and western blot were used to verify the up-regulated expression levels of the selected key genes. Results: Within the co-expression modules constructed by WGCNA, the MElightcyan module exhibited the strongest positive correlation with lupus nephritis (0.4, P = 0.003), while showing a weaker correlation with the control group SLE (0.058) and a negative correlation with the control group (-0.41, P = 0.002). Additionally, the MEgreenyellow module displayed the highest positive correlation with SLE (0.25), but its P value was 0.06, which did not reach statistical significance(P > 0.05). Furthermore, it had a negative correlation with the control group was (-0.38, P = 0.004). The module associated with lupus nephritis was characterized by processes such as neutrophil activation (neutrophil_activation), neutrophil degranulation (neutrophil_degranulation), neutrophil activation involved in immune response (neutrophil_activation_involved_in_immune_response), neutrophils mediated immune (neutrophil_mediated_immunity) and white blood cells degranulation (leukocyte_degranulation) and so on the adjustment of the process. Secondly, in the analysis of SLE samples, the identification of differentially expressed genes revealed 125 genes, with 49 being up-regulated and 76 down-regulated. In the case of lupus nephritis samples, 156 differentially expressed genes were discerned, include in 70 up-regulated and 86 down-regulated genes. When examining differential methylation sites, we observed 12432 such sites in the SLE sample analysis, encompassing 2260 hypermethylation sites and 10172 hypomethylation sites. In the lupus nephritis samples analysis, 9613 differential methylation sites were identified, comprising 4542 hypermethylation sites and 5071 hypomethylation sites. Substantiating our findings, experimental validation of the up-regulated genes in lupus nephritis confirmed increased levels of gene expression and protein expression for CEACAM1 and SLC2A5. Conclusions: We have identified several genes, notably CEACAM1 and SLC2A5, as potential markers for lupus nephritis. Their elevated expression levels and reduced DNA methylation in lupus nephritis contribute to a more comprehensive understanding of the aberrant epigenetic regulation of expression in this condition. These findings hold significant implications for the diagnosis and therapeutic strategies of lupus nephritis.
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The escalating menace of antimicrobial resistance (AMR) presents a profound global threat to life and assets. However, the incapacity of metal ions/reactive oxygen species (ROS) or the indiscriminate intrinsic interaction of cationic groups to distinguish between bacteria and mammalian cells undermines the essential selectivity required in these nanomaterials for an ideal antimicrobial agent. Hence, we devised and synthesized a range of biocompatible mixed-charge hyperbranched polymer nanoparticles (MCHPNs) incorporating cationic, anionic, and neutral alkyl groups to effectively combat multidrug-resistant bacteria and mitigate AMR. This outcome stemmed from the structural, antibacterial activity, and biocompatibility analysis of seven MCHPNs, among which MCHPN7, with a ratio of cationic groups, anionic groups, and long alkyl chains at 27:59:14, emerged as the lead candidate. Importantly, owing to inherent differences in membrane potential among diverse species, alongside its nano-size (6-15 nm) and high hydrophilicity (Kow = 0.04), MCHPN7 exhibited exceptional selective bactericidal effects over mammalian cells (selectivity index > 564) in vitro and in vivo. By inducing physical membrane disruption, MCHPN7 effectively eradicated antibiotic-resistant bacteria and significantly delayed the emergence of bacterial resistance. Utilized as a coating, MCHPN7 endowed initially inert surfaces with the ability to impede biofilm formation and mitigate infection-related immune responses in mouse models. This research heralds the advent of biocompatible polymer nanoparticles and harbors significant implications in our ongoing combat against AMR. STATEMENT OF SIGNIFICANCE: The escalating prevalence of antimicrobial resistance (AMR) has been acknowledged as one of the most significant threats to global health. Therefore, a series of mixed-charge hyperbranched polymer nanoparticles (MCHPNs) with selective antibacterial action were designed and synthesized. Owing to inherent differences in membrane potential among diverse species and high hydrophilicity (Kow = 0.04), the optimal nanoparticles exhibited exceptional selective bactericidal effects over mammalian cells (selectivity index >564) and significantly delayed the emergence of bacterial resistance. Importantly, they endowed surfaces with the ability to impede biofilm formation and mitigate infection-related immune responses. Furthermore, the above findings focus on addressing the problem of AMR in Post-Pandemic, which will for sure attract attention from both academic and industry research.
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Computer-aided diagnosis (CAD) has advanced medical image analysis, while large language models (LLMs) have shown potential in clinical applications. However, LLMs struggle to interpret medical images, which are critical for decision-making. Here we show a strategy integrating LLMs with CAD networks. The framework uses LLMs' medical knowledge and reasoning to enhance CAD network outputs, such as diagnosis, lesion segmentation, and report generation, by summarizing information in natural language. The generated reports are of higher quality and can improve the performance of vision-based CAD models. In chest X-rays, an LLM using ChatGPT improved diagnosis performance by 16.42 percentage points compared to state-of-the-art models, while GPT-3 provided a 15.00 percentage point F1-score improvement. Our strategy allows accurate report generation and creates a patient-friendly interactive system, unlike conventional CAD systems only understood by professionals. This approach has the potential to revolutionize clinical decision-making and patient communication.
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In order to further enhance the erosion resistance of cement concrete pavement materials, this study constructed an apparent rough hydrophobic structure layer by spraying a micro-nano substrate coating on the surface layer of the cement concrete pavement. This was followed by a secondary spray of a hydroxy-silicone oil-modified epoxy resin and a low surface energy-modified substance paste, which combine to form a superhydrophobic coating. The hydrophobic mechanism of the coating was then analysed. Firstly, the effects of different types and ratios of micro-nano substrates on the apparent morphology and hydrophobic performance of the rough structure layer were explored through contact angle testing and scanning electron microscopy (SEM). Subsequently, Fourier transform infrared spectroscopy and permeation gel chromatography were employed to ascertain the optimal modification ratio, temperature, and reaction mechanism of hydroxy-silicone oil with E51 type epoxy resin. Additionally, the mechanical properties of the modified epoxy resin-low surface energy-modified substance paste were evaluated through tensile tests. Finally, the erosion resistance of the superhydrophobic coating was tested under a range of conditions, including acidic, alkaline, de-icer, UV ageing, freeze-thaw cycles and wet wheel wear. The results demonstrate that relying solely on the rough structure of the concrete surface makes it challenging to achieve superhydrophobic performance. A rough structure layer constructed with diamond micropowder and hydrophobic nano-silica is less prone to cracking and can form more "air chamber" structures on the surface, with better wear resistance and hydrophobic performance. The ring-opening reaction products that occur during the preparation of modified epoxy resin will severely affect its mechanical strength after curing. Controlling the reaction temperature and reactant ratio can effectively push the modification reaction of epoxy resin through dehydration condensation, which produces more grafted polymer. It is noteworthy that the grafted polymer content is positively correlated with the hydrophobicity of the modified epoxy resin. The superhydrophobic coating exhibited enhanced erosion resistance (based on hydrochloric acid), UV ageing resistance, abrasion resistance, and freeze-thaw damage resistance to de-icers by 19.41%, 18.36%, 43.17% and 87.47%, respectively, in comparison to the conventional silane-based surface treatment.
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Groenlandicine is a protoberberine alkaloid isolated from Coptidis Rhizoma, a widely used traditional Chinese medicine known for its various biological activities. This study aims to validate groenlandicine's effect on both cisplatin-sensitive and cisplatin-resistant osteosarcoma (OS) cells, along with exploring its potential molecular mechanism. The ligand-based virtual screening (LBVS) method and molecular docking were employed to screen drugs. CCK-8 and FCM were used to measure the effect of groenlandicine on the OS cells transfected by lentivirus with over-expression or low-expression of TOP1. Cell scratch assay, CCK-8, FCM, and the EdU assay were utilized to evaluate the effect of groenlandicine on cisplatin-resistant cells. WB, immunofluorescence, and PCR were conducted to measure the levels of TOP1, Bcl-2, BAX, Caspase-9, and Caspase-3. Additionally, a subcutaneous tumor model was established in nude mice to verify the efficacy of groenlandicine. Groenlandicine reduced the migration and proliferation while promoting apoptosis in OS cells, effectively damaging them. Meanwhile, groenlandicine exhibited weak cytotoxicity in 293T cells. Combination with cisplatin enhanced tumor-killing activity, markedly activating BAX, cleaved-Caspase-3, and cleaved-Caspase-9, while inhibiting the Bcl2 pathway in cisplatin-resistant OS cells. Moreover, the level of TOP1, elevated in cisplatin-resistant OS cells, was down-regulated by groenlandicine both in vitro and in vivo. Animal experiments confirmed that groenlandicine combined with cisplatin suppressed OS growth with lower nephrotoxicity. Groenlandicine induces apoptosis and enhances the sensitivity of drug-resistant OS cells to cisplatin via the BAX/Bcl-2/Caspase-9/Caspase-3 pathway. Groenlandicine inhibits OS cells growth by down-regulating TOP1 level.Therefore, groenlandicine holds promise as a potential agent for reversing cisplatin resistance in OS treatment.
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Skeletal muscle development is spotlighted in mammals since it closely relates to animal health and economic benefits to the breeding industry. Researchers have successfully unveiled many regulatory factors and mechanisms involving myogenesis. However, the effect of N6-methyladenosine (m6A) modification, especially demethylase and its regulated genes, on muscle development remains to be further explored. Here, we found that the typical demethylase FTO (fat mass- and obesity-associated protein) was highly enriched in goats' longissimus dorsi (LD) muscles. In addition, the level of m6A modification on transcripts was negatively regulated by FTO during the proliferation of goat skeletal muscle satellite cells (MuSCs). Moreover, a deficiency of FTO in MuSCs significantly retarded their proliferation and promoted the expression of dystrophin-associated protein 1 (DAG1). m6A modifications of DAG1 mRNA were efficiently altered by FTO. Intriguingly, the results of DAG1 levels and its m6A enrichment from FB23-2 (FTO demethylase inhibitor)-treated cells were consistent with those of the FTO knockdown, indicating that the regulation of FTO on DAG1 depended on m6A modification. Further experiments showed that interfering FTO improved m6A modification at site DAG1-122, recognized by Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) and consequently stabilized DAG1 transcripts. Our study suggests that FTO promotes the proliferation of MuSCs by regulating the expression of DAG1 through m6A modification. This will extend our knowledge of the m6A-related mechanism of skeletal muscle development in animals.
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Adenosina , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato , Cabras , ARN Mensajero , Células Satélite del Músculo Esquelético , Animales , Adenosina/análogos & derivados , Adenosina/metabolismo , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/metabolismo , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/genética , Proliferación Celular , Células Cultivadas , Desarrollo de Músculos , Estabilidad del ARN , ARN Mensajero/metabolismo , ARN Mensajero/genética , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética , Células Satélite del Músculo Esquelético/metabolismo , Células Satélite del Músculo Esquelético/citologíaRESUMEN
BACKGROUND: The anti-pruritic effect of placebo in patients with chronic urticaria has gained increasing attention in clinical research. However, the extent of placebo effect and its influencing factors in the treatment of chronic urticaria are not well understood. OBJECTIVE: The objective of this systematic review and meta-analysis was to investigate the effect of placebo on pruritus in patients with chronic urticaria and to explore relevant influencing factors. METHODS: PubMed, Embase, Web of Science, Cochrane Library, and PsycINFO were searched from inception to 10 July, 2024. Primary outcome included pruritus scores. The secondary outcomes focused on global symptoms and quality of life. Subgroup analyses and meta-regression analyses were conducted based on drug types, sample size, participants' age, and other variables. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system and a trial sequential analysis were employed to establish the reliability of evidence. RESULTS: A total of 65 eligible publications (including 67 randomized controlled trials) involving 10,704 patients with chronic urticaria were included. The pruritus scores decreased following placebo treatment (moderate evidence). In addition, favorable results were observed in global symptoms (moderate evidence) and quality of life (low evidence) after placebo treatment. Subgroup analyses indicated that the type of active medication in intervention groups was an influencing factor of placebo effect of pruritus. Meta-regression analyses demonstrated that the anti-pruritic effect of placebo was inversely correlated with sample size and positively correlated with participants' age. A trial sequential analysis provided further support for the anti-pruritic effect of placebo. CONCLUSIONS: A substantial improvement of pruritus after placebo treatment was observed in patients with chronic urticaria. The anti-pruritic effect of placebo varied with sample size, participants' age, and type of active medication used. Future research should further investigate the effect size of placebo and clarify the potential mechanism. PROSPERO REGISTRATION: The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) as CRD42023482608.
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Urticaria Crónica , Efecto Placebo , Prurito , Humanos , Urticaria Crónica/tratamiento farmacológico , Placebos , Prurito/tratamiento farmacológico , Prurito/etiología , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Organic red/near-infrared (NIR) room temperature phosphorescence (RTP) materials with low toxicity and facile synthesis are highly sought after, particularly for applications in biotechnology and encryption. However, achieving efficient red/NIR RTP emitters has been challenging due to the weak spin-orbit coupling of organics and the rapid nonradiative decay imposed by the energy gap law. Here we demonstrate highly efficient red/NIR RTP with boosted quantum yields (Φps) of up to 32.96 % through doping the thionated derivatives of phthalimide (PAI) (MTPAI and DTPAI) into PAI crystals. The red-shifted photoluminescence (PL) stems from a combination of the external heavy atom effect and the formation of emissive clusters centered around electron-rich sulfur atoms. Furthermore, the dopants enhance exciton generation efficiency and facilitate energy transfer from smaller PAI units to larger aggregates, leading to dramatically increased Φp. This strategy proves universal, opening possibilities for acquiring long-wavelength RTP with tunable photophysical properties. The doped crystals exhibit promising applications in optical waveguides and encryption paper/ink. This research provides a practical approach to obtaining long-wavelength RTP materials and offers valuable insights into the mechanisms governing host-guest systems.
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The anterior gradient protein 2 (AGR2) plays a crucial role in facilitating the formation of protein disulfide bonds within the endoplasmic reticulum (ER). Research suggests that AGR2 can function as an oncogene, with its heightened expression linked to the advancement of hepatobiliary and pancreatic cancers through invasion and metastasis. Notably, AGR2 not only serves as a pro-oncogenic agent but also as a downstream targeting protein, indirectly fostering cancer progression. This comprehensive review delves into the established functions and expression patterns of AGR2, emphasizing its pivotal role in cancer progression, particularly in hepatobiliary and pancreatic malignancies. Furthermore, AGR2 emerges as a potential cancer prognostic marker and a promising target for immunotherapy, offering novel avenues for the treatment of hepatobiliary and pancreatic cancers and enhancing patient outcomes.
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Mucoproteínas , Proteínas Oncogénicas , Neoplasias Pancreáticas , Humanos , Mucoproteínas/metabolismo , Mucoproteínas/genética , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/terapia , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/patología , Proteínas Oncogénicas/metabolismo , Proteínas Oncogénicas/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patología , Animales , Neoplasias del Sistema Biliar/genética , Neoplasias del Sistema Biliar/metabolismo , Neoplasias del Sistema Biliar/tratamiento farmacológico , Neoplasias del Sistema Biliar/terapia , Neoplasias del Sistema Biliar/patología , Regulación Neoplásica de la Expresión Génica , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/genéticaRESUMEN
Bismuth-based halide perovskites have shown great potential for direct X-ray detection, attributable to their nontoxicity and advantages in detection sensitivity and spatial resolution. However, the practical application of such materials still faces the critical challenge of combining both high sensitivity and low detection limits. Here, we report a new type of zero-dimensional (0D) perovskite (HIS)BiI5 (1, where HIS2+ = histamine) with high sensitivity and a low detection limit. Structurally, the strong N-H···I hydrogen bonds between HIS2+ cations and inorganic frameworks enhance the rigidity of the structure and diminish the intermolecular distance between adjacent inorganic [Bi2I10]4- dimers. By virtue of such structural merits, single crystal 1 exhibits excellent physical properties perpendicular to both the (001) and (010) faces. Perpendicular to the (010) face, 1 exhibited a high electrical resistivity (2.31 × 1011 Ω cm) and a large carrier mobility-lifetime product (µτ) (2.81 × 10-4 cm2 V-1) under X-ray illumination. Benefiting from these superior physical properties, it demonstrates an excellent X-ray detection capability with a sensitivity of approximately 103 µC Gyair-1 cm-2 and a detection limit of 36 nGyair s-1 in both directions perpendicular to the (001) and (010) crystal faces. These results provide a promising candidate material for the development of new, lead-free, high-performance X-ray detectors.
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Proteins in the open ocean represent a significant source of organic matter, and their profiles reflect the metabolic activities of marine microorganisms. Here, by analyzing metaproteomic samples collected from the Pacific, Atlantic and Southern Ocean, we reveal size-fractionated patterns of the structure and function of the marine microbiota protein pool in the water column, particularly in the dark ocean (>200 m). Zooplankton proteins contributed three times more than algal proteins to the deep-sea community metaproteome. Gammaproteobacteria exhibited high metabolic activity in the deep-sea, contributing up to 30% of bacterial proteins. Close virus-host interactions of this taxon might explain the dominance of gammaproteobacterial proteins in the dissolved fraction. A high urease expression in nitrifiers suggested links between their dark carbon fixation and zooplankton urea production. In summary, our results uncover the taxonomic contribution of the microbiota to the oceanic protein pool, revealing protein fluxes from particles to the dissolved organic matter pool.
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Proteínas Bacterianas , Gammaproteobacteria , Microbiota , Océanos y Mares , Proteómica , Agua de Mar , Zooplancton , Proteómica/métodos , Zooplancton/metabolismo , Agua de Mar/microbiología , Agua de Mar/química , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Gammaproteobacteria/metabolismo , Gammaproteobacteria/genética , Animales , Proteoma/metabolismo , Cadena Alimentaria , Ciclo del CarbonoRESUMEN
Photoluminescence (PL) colour-changing materials in response to photostimulus play an increasingly significant role in intelligent applications for their programmability. Nevertheless, current research mainly focuses on photochemical processes, with less attention to PL transformation through uniform aggregation mode adjustment. Here we show photochromic luminescence in organic crystals (e.g. dimethyl terephthalate) with PL varying from dark blue to purple, then to bright orange-red, and finally to red. This change is attributed to the emergence of clusters with red emission, which is barely achieved in single-benzene-based structures, thanks to the subtle molecular rearrangements prompted by light. Crucial to this process are the through-space electron interactions among molecules and moderate short contacts between ester groups. The irradiated crystals exhibit reversible PL transformation upon sufficient relaxation, showing promising applications in information storage and smart optoelectronic devices. This research contributes to the development of smart photochromic luminescent materials with significant PL colour transformations through molecular rearrangement.
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The integration of Computer-Aided Diagnosis (CAD) with Large Language Models (LLMs) presents a promising frontier in clinical applications, notably in automating diagnostic processes akin to those performed by radiologists and providing consultations similar to a virtual family doctor. Despite the promising potential of this integration, current works face at least two limitations: (1) From the perspective of a radiologist, existing studies typically have a restricted scope of applicable imaging domains, failing to meet the diagnostic needs of different patients. Also, the insufficient diagnostic capability of LLMs further undermine the quality and reliability of the generated medical reports. (2) Current LLMs lack the requisite depth in medical expertise, rendering them less effective as virtual family doctors due to the potential unreliability of the advice provided during patient consultations. To address these limitations, we introduce ChatCAD+, to be universal and reliable. Specifically, it is featured by two main modules: (1) Reliable Report Generation and (2) Reliable Interaction. The Reliable Report Generation module is capable of interpreting medical images from diverse domains and generate high-quality medical reports via our proposed hierarchical in-context learning. Concurrently, the interaction module leverages up-to-date information from reputable medical websites to provide reliable medical advice. Together, these designed modules synergize to closely align with the expertise of human medical professionals, offering enhanced consistency and reliability for interpretation and advice. The source code is available at GitHub.
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Sinking particles are a critical conduit for the transport of surface microbes to the ocean's interior. Vertical connectivity of phylogenetic composition has been shown; however, the functional vertical connectivity of microbial communities has not yet been explored in detail. We investigated protein and taxa profiles of both free-living and particle-attached microbial communities from the surface to 3000 m depth using a combined metaproteomic and 16S rRNA amplicon sequencing approach. A clear compositional and functional vertical connectivity of microbial communities was observed throughout the water column with Oceanospirillales, Alteromonadales, and Rhodobacterales as key taxa. The surface-derived particle-associated microbes increased the expression of proteins involved in basic metabolism, organic matter processing, and environmental stress response in deep waters. This study highlights the functional vertical connectivity between surface and deep-sea microbial communities via sinking particles and reveals that a considerable proportion of the deep-sea microbes might originate from surface waters and have a major impact on the biogeochemical cycles in the deep sea.