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Immunosuppressive tumor microenvironment (ITM) severely limited the efficacy of immunotherapy against triple-negative breast cancer (TNBC). Herein, Apt-LPR, a light-activatable photodynamic therapy (PDT)/RNAi immune synergy-enhancer was constructed by co-loading miR-34a and photosensitizers in cationic liposomes (in phase III clinical trial). Interestingly, the introduction of tumor-specific aptamers creates a special "Liposome-Aptamer-Target" interface, where the aptamers are initially in a "lying down" state but transform to "standing up" after target binding. The interfacing mechanism was elaborately revealed by computational and practical experiments. This unique interface endowed Apt-LPR with neutralized surface potential of cationic liposomes to reduce non-specific cytotoxicity, enhanced DNase resistance to protect aptamers, and preserved target-binding ability for selective drug delivery. Upon near-infrared irradiation, the generated reactive oxygen species would oxidize unsaturated phospholipids to destabilize both liposomes and lysosomes, realizing stepwise lysosomal escape of miR-34a for tumor cell apoptosis and downregulation of PD-L1 to suppress immune escape. Together, tumor-associated antigens released from PDT-damaged mitochondria and endoplasmic reticulum could activate the suppressive immune cells to establish an "immune hot" milieu. The collaborative immune-enhancing strategy effectively aroused systemic antitumor immunity and inhibited primary and distal tumor progression as well as lung metastasis in 4T1 xenografted mouse models. The photo-controlled drug release and specific tumor-targeting capabilities of Apt-LPR were also visualized in MDA-MB-231 xenografted zebrafish models. Therefore, this photoswitchable PDT/RNAi immune stimulator offered a powerful approach to reprogramming ITM and reinforcing cancer immunotherapy efficacy.
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Lipossomos , MicroRNAs , Fotoquimioterapia , Fármacos Fotossensibilizantes , Neoplasias de Mama Triplo Negativas , Microambiente Tumoral , Animais , Humanos , Lipossomos/química , MicroRNAs/genética , MicroRNAs/metabolismo , Fotoquimioterapia/métodos , Microambiente Tumoral/efeitos dos fármacos , Linhagem Celular Tumoral , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Feminino , Neoplasias de Mama Triplo Negativas/terapia , Neoplasias de Mama Triplo Negativas/patologia , Camundongos , Aptâmeros de Nucleotídeos/química , Preparações de Ação Retardada/química , Interferência de RNA , Peixe-ZebraRESUMO
Bioelectronic implants featuring soft mechanics, excellent biocompatibility, and outstanding electrical performance hold promising potential to revolutionize implantable technology. These biomedical implants can record electrophysiological signals and execute direct therapeutic interventions within internal organs, offering transformative potential in the diagnosis, monitoring, and treatment of various pathological conditions. However, challenges remain in improving excessive impedance at the bioelectronic-tissue interface and thus the efficacy of electrophysiological signaling and intervention. Here, we devise orbit symmetry breaking in MXene (a low-cost scalability, biocompatible, and conductive two dimensionally layered material, which we refer to as OBXene), which exhibits low bioelectronic-tissue impedance, originating from the out-of-plane charge transfer. Furthermore, the Schottky-induced piezoelectricity stemming from the asymmetric orbital configuration of OBXene facilitates interlayered charge transport in the device. We report an OBXene-based cardiac patch applied on the left ventricular epicardium of both rodent and porcine models to enable spatiotemporal epicardium mapping and pacing while coupling the wireless and battery-free operation for long-term real-time recording and closed-loop stimulation.
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Próteses e Implantes , Animais , Suínos , Órbita/cirurgia , Impedância Elétrica , Materiais Biocompatíveis/químicaRESUMO
The wilt disease of ginger, caused by various Fusarium species, imperils the cultivation of this valuable crop. However, the pathogenic mechanisms and epidemiology of ginger wilt remain elusive. Here, we investigate the association between ginger rhizome health and the prevalence of Fusarium conidia, as well as examine fungal community composition in symptomatic and asymptomatic ginger tissues. Our findings show that diseased rhizomes have reduced tissue firmness, correlating negatively with Fusarium conidia counts. Pathogenicity assays confirmed that both Fusarium oxysporum and Fusarium solani are capable of inducing wilt symptoms in rhizomes and sterile seedlings. Furthermore, Fungal community profiling revealed Fusarium to be the dominant taxon across all samples, yet its relative abundance was significantly different between symptomatic and asymptomatic tissues. Specifically, there is a higher incidence of Fusarium amplicon sequence variants (ASVs) in symptomatic above-ground parts. Our results unequivocally implicate F. oxysporum or F. solani as the etiological agents responsible for ginger wilt and demonstrate that Fusarium is the principal fungal pathogen associated with this disease. These findings provide critical insights for efficacious disease management practices within the ginger industry.
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Fast steering mirrors (FSMs) offer a potential alternative for large-range deflection of light beams. However, for a large-stroke FSM, its pointing precision is unacceptably deteriorated due to the actuator non-uniformity, mechanical axis coupling, and the coupling of line-of-sight (LOS) kinematics. This Letter proposes a comprehensive beam-pointing algorithm by decoupling the LOS kinematic model and establishing a two-dimensional correction mapping to compensate for the non-uniformity and mechanical coupling. Moreover, the incident angle is calibrated by a non-contact method to construct the LOS kinematic model accurately. The experimental results proved that the beam-pointing accuracy can achieve a sub-milliradian level within the square field of regard (FOR) of ±25° horizontally and ±14° vertically. A pointing error of 0.87â mrad can be guaranteed within the horizontal range of -30° to 36° and the vertical range of ±24°. Therefore, the proposed method can achieve high-precision beam pointing in a large FOR and contributes to the miniaturization of optical systems.
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The genus Quercus L. is widely acknowledged as a significant assemblage within East Asia tropical and subtropical broadleaf evergreen forests, possessing considerable economic importance. Nevertheless, the differentiation of Quercus species is deemed arduous, and the interrelations among these species remain enigmatic. Leveraging Illumina sequencing, we undertook the sequencing and assembly of the chloroplast (cp) genomes of seven species belonging to Quercus section Cyclobalanopsis (Quercus argyrotricha, Q. augustinii, Q. bambusifolia, Q. bella, Q. edithiae, Q. jenseniana, and Q. poilanei). Furthermore, we collated three previously published cp genome sequences of Cyclobalanopsis species (Q. litseoides, Q. obovatifolia, and Q. saravanensis). Our primary objective was to conduct comparative genomics and phylogenetic analyses of the complete cp genomes of ten species from Quercus section Cyclobalanopsis. This investigation unveiled that Quercus species feature a characteristic circular tetrad structure, with genome sizes ranging from 160,707 to 160,999 base pairs. The genomic configuration, GC content, and boundaries of inverted repeats/single copy regions exhibited marked conservation. Notably, four highly variable hotspots were identified in the comparative analysis, namely trnK-rps16, psbC-trnS, rbcL-accD, and ycf1. Furthermore, three genes (atpF, rpoC1, and ycf2) displayed signals of positive selection pressure. Phylogenetic scrutiny revealed that the four sections of Cyclobalanopsis clustered together as sister taxa. The branch support values ranged from moderate to high, with most nodes garnering 100% support, underscoring the utility of cp genomic data in elucidating the relationships within the genus. Divergence time analysis revealed that Section Cyclobalanopsis represents the earliest type of Quercus genus. The outcomes of this investigation establish a foundation for forthcoming research endeavors in taxonomy and phylogenetics.
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Background: Ovarian cancer (OC) remains the deadliest gynecologic malignancy worldwide due to delayed diagnosis, recurrence, and drug resistance. This study aimed to identify key factors affecting delayed diagnosis in OC patients. Methods: A retrospective analysis was conducted on OC patients treated at Taihe Hospital, Hubei University of Medicine from June 2023 to September 2023. Patients were categorized based on a three-months cut-off point for delayed diagnosis. Collected data included demographics, tumor incidence, and disease cognition. The analysis of variance and the chi-squared test was used for comparison between groups. Results: The significant differences were found in age, residence, education level, family income, family history of tumor, histology, FIGO stage, and tumor location between groups (P<0.05). Multifactorial logistic regression analysis identified education level [odds ratio (OR) = 0.606; 95% confidence interval (CI): 0.440, 0.833; P = 0.002], family history of tumor (OR = 0.462; 95% CI: 0.214, 0.997; P = 0.049), emotional barriers (OR = 1.332; 95% CI: 1.081, 1.642; P = 0.007), and practical barriers (OR = 2.964; 95% CI: 2.195, 4.004; P < 0.001) as risk factors for delayed diagnosis of OC. Conclusion: Patient cognition is crucial in OC diagnosis delay. Enhancing public awareness and understanding of OC is essential to eliminate fear and improve early diagnosis.
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In photoelectrochemical (PEC) sensors, traditional detection modes such as "signal-on", "signal-off", and "polarity-switchable" limit target signals to a single polarity range, necessitating novel design strategies to enhance the operational scope. To overcome this limitation, we propose, for the first time, a "polarity-transcendent" design concept that enables a continuous response across the polarity spectrum, significantly broadening the sensor's concentration detection range. This concept is exemplified in our new "background-enhanced signal-off polarity-switchable" (BESOPS) mode, where the model analyte let-7a activates a cascade shearing reaction of a DNAzyme walker in conjunction with CRISPR/Cas12a, quantitatively peeling off Cu2O-H2 strands at the Cu2O/TiO2 electrode interface to expose the TiO2 surface. This exposure generates an anodic photocurrent at the expense of the cathodic photocurrent from Cu2O/TiO2, facilitating a seamless transition of the target signal from cathodic to anodic. Through systematic experiments and comparative analyses, the BESOPS sensor demonstrates highly sensitive and precise quantification of let-7a, with a detection limit of 2.5 aM and a broad operating range of 10 aM to 10 nM. Its performance exceeds most reported sensor platforms, highlighting the significant potential of our polarity-transcendent design in expanding the operational range of PEC sensors. This innovative approach paves the way for developing next-generation PEC sensors with enhanced applicability and heightened sensitivity in various critical fields.
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Técnicas Biossensoriais , Cobre , Técnicas Eletroquímicas , Limite de Detecção , Titânio , Técnicas Biossensoriais/instrumentação , Técnicas Eletroquímicas/métodos , Cobre/química , Titânio/química , MicroRNAs/análise , Humanos , Desenho de Equipamento , Sistemas CRISPR-Cas , EletrodosRESUMO
Developing rapid and sensitive methods for monitoring inorganic mercury (Hg2+) and methylmercury (CH3Hg+) in crayfish is crucial for understanding the environmental impact of these contaminants. In this work, a novel tri-mode strategy was developed for highly sensitive monitoring of Hg2+ and CH3Hg+ bioaccumulation in crayfish by inductively coupled plasma mass spectrometry (ICP-MS)/ fluorescence /smartphone colorimetric (RGB) analysis without chromatographic separation. Cation exchange reaction (CER) was performed between Hg2+ and luminescent CdTe quantum dots (QDs), while CH3Hg+ unrealizable CER. The CH3Hg+ can be transformed to Hg2+ by simple UV irradiation, speciation analysis can be realized by detecting the fluorescence of CdTe QDs after incubation by Hg2+ and total Hg2+. In addition, the filtration of reacted CdTe QDs was carried out, ICP-MS was performed to detect exchanged Cd2+ by Hg2+ and total Hg2+, as well the smartphone RGB analysis was performed for membrane colorimetry. The limits of detection (LODs) of Hg2+ and CH3Hg+ for ICP-MS, fluorescence, and colorimetric (RGB) modes were 0.03 ng mL-1, 18 ng mL-1, and 0.9 µg mL-1 respectively. Density Functional Theory (DFT) was employed to validate the mechanism of the CER reaction. CdTe QDs array analysis with five different ligands was performed to eliminate potential ion interferences of Ag+ and Cu2+ that could occur during the CER reaction. The well-designed system was successfully utilized for monitoring trace Hg2+ and CH3Hg+ in crayfish fed Hg2+ and CH3Hg+ contaminative food over a two-week "uptake" period and a three-week "depuration" period. The results indicated that the Hg2+ uptake in different tissues was significantly different from that of CH3Hg+ in all tissues. There was evidence of Hg uptake from water via leaching from food, although the principal source of uptake was from food.
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The extensive use of neonicotinoids (NEOs) in agricultural production has led to their pervasive presence in various environmental matrices, including human samples. Given the central role of fruits and vegetables in daily human diets, it is crucial to evaluate the levels of NEOs residues and their potential health risks. In this study, 3104 vegetable samples and 1567 fruit samples from the Shenzhen city were analyzed. Using the relative potency factor (RPF) method, the residue levels of six representative neonicotinoids, including imidacloprid (IMI), acetamiprid (ACE), thiamethoxam (THM), dinotefuran (DIN), clothianidin (CLO), thiacloprid (THI), were systematically evaluated. The estimated daily intake (EDI), hazard quotient (HQ), and hazard index (HI) for both children and adults were calculated to gauge the prevalence and potential health risks of NEOs in fruits and vegetables. Acetamiprid (ACE) was the most frequently detected NEO in vegetables (69.4%) and fruits (73.9%), making it the predominant contributor to total residues. Further analyses indicated notably higher levels of imidacloprid-equivalent total neonicotinoids (IMIRPF) in root and tuber vegetables (3025 µg/kg) and other fruits (243 µg/kg). A significant strong positive correlation (r = 0.748, P < 0.05) was observed between thiamethoxam (THM) and clothianidin (CLO), possibly due to their shared metabolic pathways. Although the mean HI values for adults and children from daily fruit (adults: 0.02, children: 0.01) and vegetable (adults: 0.02, children: 0.03) intake were generally below safety thresholds, some maximum HI values exceeded these limits, indicating that the potential health risks associated with NEOs exposure should not be overlooked.
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Frutas , Neonicotinoides , Resíduos de Praguicidas , Verduras , Neonicotinoides/análise , Humanos , Verduras/química , Frutas/química , Resíduos de Praguicidas/análise , China , Medição de Risco , Nitrocompostos/análise , Guanidinas/análise , Inseticidas/análise , Exposição Ambiental/estatística & dados numéricos , Exposição Ambiental/análise , Tiametoxam/análise , Contaminação de Alimentos/análise , Monitoramento Ambiental , Tiazinas , TiazóisRESUMO
Background: The worldwide geographical and temporal variation in the prevalence of diabetes represents a challenge, but also an opportunity for gaining etiological insights. Encompassing the bulk of East Asians, a large and distinct proportion of the world population, China can be a source of valuable epidemiological insights for diabetes, especially in early life, when pathophysiology begins. We carried out a nationwide, epidemiological survey of Prevalence and Risk of Obesity and Diabetes in Youth (PRODY) in China, from 2017 to 2019, to estimate the population-based prevalence of diagnosed pediatric diabetes and screen for undiagnosed pediatric type 2 diabetes (T2D). Methods: PRODY was a nation-wide, school population-based, cross-sectional, multicenter survey by questionnaire, fasting urine glucose test and simple oral glucose tolerance test (s-OGTT), among a total number of 193,801 general-population children and adolescents (covered a pediatric population of more than 96.8 million), aged 3-18, from twelve provinces across China. The prevalence of the self-reported pediatric diabetes, the proportion of subtypes, the crude prevalence of undiagnosed T2D and prediabetes in general juvenile population and the main risk factors of type 1 (T1D) and type 2 (T2D) diabetes had been analyzed in the study. Findings: The prevalence of all self-reported pediatric diabetes was estimated at 0.62/1000 (95% CI: 0.51-0.74), with T1D at 0.44/1000 (95% CI: 0.35-0.54) and T2D at 0.18/1000 (95% CI: 0.13-0.25). For undiagnosed T2D, the crude prevalence was almost ten-fold higher, at 1.59/1000, with an estimated extra 28.45/1000 of undiagnosed impaired glucose tolerance (IGT) and 53.74/1000 of undiagnosed impaired fasting glucose (IFG) by s-OGTT screening. Maternal diabetes history is the major risk factors for all subtypes of pediatric diabetes in China. Interpretation: The PRODY study provides the first population-based estimate of the prevalence of pediatric diabetes China and reveals a magnitude of the problem of undiagnosed pediatric T2D. We propose a practical screening strategy by s-OGTT to address this serious gap. Funding: The National Key Research and Development Programme of China, Key R&D Program of Zhejiang, the National Natural Science Foundation of China and the Zhejiang Provincial Key Disciplines of Medicine, Key R&D Program Projects in Zhejiang Province.
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Microbial extracellular enzymatic activities (EEAs) produced by microbes to degrade biopolymers are the 'gatekeeper' of carbon cycle in the marine ecosystem. It is usually assumed that these extracellular enzymes are actively secreted by microbes. But biopolymers degrading enzymes also exist in the intracellular space. Cell lysis will passively release these enzymes into the environments and contribute to the total EEAs. However, to what extent the cell lysis can contribute to the total EEAs are still unclear. Here, using extreme cell lysis method, we evaluated the maximum contribution of cell lysis to total EEAs in culturable marine bacteria and coastal seawater. For carbohydrate processing enzymes (ß-glucosidase, alginate lyase and chitinase), the release of intracellular enzymes could contribute positively (up to 56.1% increase for ß-glucosidase in seawater) to the total EEAs. For protease and leucine aminopeptidase, the cell lysis did not increase and even decreased the total EEAs. For alkaline phosphatase, the intracellular enzymes generally had no contribution to the total EEAs. These results showed that passively released intracellular enzymes could substantially increase the total extracellular activities of carbohydrate processing enzymes, which should be considered in building the link between the EEAs and organic carbon cycle in the ocean.
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Marine antimicrobial peptides (AMPs) represent a promising source for combating infections, especially against antibiotic-resistant pathogens and traditionally challenging infections. However, traditional drug discovery methods face challenges such as time-consuming processes and high costs. Therefore, leveraging machine learning techniques to expedite the discovery of marine AMPs holds significant promise. Our study applies machine learning to develop marine AMPs, focusing on Crassostrea gigas mucus rich in antimicrobial components. We conducted proteome sequencing of C. gigas mucous proteins, used the iAMPCN model for peptide activity prediction, and evaluated the antimicrobial, hemolytic, and cytotoxic capabilities of six peptides. Proteomic analysis identified 4490 proteins, yielding about 43,000 peptides (8-50 amino acids). Peptide ranking based on length, hydrophobicity, and charge assessed antimicrobial potential, predicting 23 biological activities. Six peptides, distinguished by their high relative scores and promising biological activities, were chosen for bactericidal assay. Peptides P1 to P4 showed antimicrobial activity against E. coli, with P2 and P4 being particularly effective. All peptides inhibited S. aureus growth. P2 and P4 also exhibited significant anti-V. parahaemolyticus effects, while P1 and P3 were non-cytotoxic to HEK293T cells at detectable concentrations. Minimal hemolytic activity was observed for all peptides even at high concentrations. This study highlights the potent antimicrobial properties of naturally occurring oyster mucus peptides, emphasizing their low cytotoxicity and lack of hemolytic effects. Machine learning accurately predicted biological activity, showcasing its potential in peptide drug discovery.
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Peptídeos Antimicrobianos , Crassostrea , Aprendizado de Máquina , Muco , Proteoma , Crassostrea/química , Animais , Muco/química , Peptídeos Antimicrobianos/farmacologia , Peptídeos Antimicrobianos/química , Humanos , Células HEK293 , Antibacterianos/farmacologia , Antibacterianos/química , Testes de Sensibilidade Microbiana , Descoberta de Drogas/métodos , Escherichia coli/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Proteômica/métodos , Vibrio parahaemolyticus/efeitos dos fármacos , Hemólise/efeitos dos fármacosRESUMO
A smartphone-mediated self-powered biosensor is fabricated for miRNA-141 detection based on the CRISPR/Cas12a cross-cutting technique and a highly efficient nanozyme. As a novel nanozyme and a signal-amplified coreaction accelerator, the AuPtPd@GDY nanozyme exhibits an excellent ability to catalyze cascade color reactions and high conductivity to enhance the electrochemical signal for miRNA-141 assays. After CRISPR/Cas12a cross-cutting of S2-glucose oxidase (S2-GOD), the electrochemical signal is weakened, and miRNA-141 is detected by monitoring the decrease in the signal. On the other hand, a cascade reaction among glucose, H2O2, and TMB is catalyzed by GOD and AuPtPd@GDY, respectively, resulting in a color change of the solution, which senses miRNA-141. The self-powered biosensor enables value-assisted and visual detection of miRNA-141 with limits of detection of 3.1 and 15 aM, respectively. Based on the dual-modal self-powered sensing system, a smartphone-mediated "all-in-one" biosensing chip is designed to achieve the real-time and intelligent monitoring of miRNA-141. This work provides a new approach to design multifunctional biosensors to realize the visualization and portable detection of tumor biomarkers.
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Técnicas Biossensoriais , MicroRNAs , Smartphone , MicroRNAs/análise , Humanos , Glucose Oxidase/metabolismo , Glucose Oxidase/química , Técnicas Eletroquímicas/métodos , Técnicas Eletroquímicas/instrumentação , Ouro/química , Limite de Detecção , Paládio/química , Sistemas CRISPR-CasRESUMO
A switchable ratiometric fluorescent smartphone-assisted sensing platform based on nitrogen-doped carbon dots (N-CDs) and Rhodamine B was fabricated for the determination of the ascorbic acid (AA) content in fruits by quenching the fluorescence of N-CDs with Hg2+ (turn-off) and recovering with AA (turn-on). The blue-emission N-CDs was synthesized by liquid dielectric barrier discharge microplasma with an average size of 3.65 nm and an absolute quantum yield of 18 % (excited at 345 nm). In addition, the fluorescence color was converted to RGB values, enabling visual and quantitative determination of AA. Under optimal parameters, the linear ranges for detecting AA were found to be 3-170 µM and 5-170 µM for fluorescence spectrometer and smartphone sensing platform. The detection limits were 0.98 µM and 2.90 µM, respectively. Furthermore, the satisfactory recoveries in fruits were obtained by RF probe and smartphone platform. This smartphone-assisted platform will facilitate sensitive and visual determination for AA.
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As global population ageing accelerates, cancer emerges as a predominant cause of mortality. Long non-coding RNAs (lncRNAs) play crucial roles in cancer cell growth and death, given their involvement in regulating downstream gene expression levels and numerous cellular processes. Cell death, especially non-apoptotic regulated cell death (RCD), such as ferroptosis, pyroptosis and necroptosis, significantly impacts cancer proliferation, invasion and metastasis. Understanding the interplay between lncRNAs and the diverse forms of cell death in cancer is imperative. Modulating lncRNA expression can regulate cancer onset and progression, offering promising therapeutic avenues. This review discusses the mechanisms by which lncRNAs modulate non-apoptotic RCDs in cancer, highlighting their potential as biomarkers for various cancer types. Elucidating the role of lncRNAs in cell death pathways provides valuable insights for personalised cancer interventions.
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We illustrated a rare case of malignant solitary fibrous tumor (MSFT) with epithelioid morphology in the occipital region of a 59-year-old female, in which a rare NAB2ex7-STAT6 exon15/16 double fusion subtype was detected by the Next-generation sequencing (NGS) and STAT6 immunohistochemistry (IHC) was diffusely and strongly positively expressed, without recurrence after 20 months of postoperative follow-up. The morphological and molecular genetic aspects and the differential diagnosis are described, and the relevant literature was assessed in order to broaden our understanding and diagnostic capability of this malignancy.
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Sex-biased gene expression differs across human populations; however, the underlying genetic basis and molecular mechanisms remain largely unknown. Here, we explore the influence of ancestry on sex differences in the human transcriptome and its genetic effects on a Eurasian admixed population: Uyghurs living in Xinjiang (XJU), by analyzing whole-genome sequencing data and transcriptome data of 90 XJU and 40 unrelated Han Chinese individuals. We identified 302 sex-biased expressed genes and 174 sex-biased cis-expression quantitative loci (sb-cis-eQTLs) in XJU, which were enriched in innate immune-related functions, indicating sex differences in immunity. Notably, approximately one-quarter of the sb-cis-eQTLs showed a strong correlation with ancestry composition; i.e. populations of similar ancestry tended to show similar patterns of sex-biased gene expression. Our analysis further suggested that genetic admixture induced a moderate degree of sex-biased gene expression. Interestingly, analysis of chromosome interactions revealed that the X chromosome acted on autosomal immunity-associated genes, partially explaining the sex-biased phenotypic differences. Our work extends the knowledge of sex-biased gene expression from the perspective of genetic admixture and bridges the gap in the exploration of sex-biased phenotypes shaped by autosome and X-chromosome interactions. Notably, we demonstrated that sex chromosomes cannot fully explain sex differentiation in immune-related phenotypes.
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Locos de Características Quantitativas , Humanos , Masculino , Feminino , Povo Asiático/genética , Transcriptoma , China , Cromossomos Humanos X/genética , Caracteres Sexuais , Genética Populacional , Regulação da Expressão Gênica , Perfilação da Expressão Gênica/métodosRESUMO
The combined stresses of fasting and hypoxia are common events during the life history of freshwater fish species. Hypoxia tolerance is vital for survival in aquatic environments, which requires organisms to down-regulate their maintenance energetic expenditure while simultaneously preserving physiological features such as oxygen supply capacity under conditions of food deprivation. Generally, infrequent-feeding species who commonly experience food shortages might evolve more adaptive strategies to cope with food deprivation than frequent-feeding species. Thus, the present study aimed to test whether the response of hypoxia tolerance in fish to short-term fasting (2 weeks) varied with different foraging modes. Fasting resulted in similar decreases in maintenance energetic expenditure and similar decreases in Pcrit and Ploe between fishes with different foraging modes, whereas it resulted in decreased oxygen supply capacity only in frequent-feeding fishes. Furthermore, independent of foraging mode, fasting decreased Pcrit and Ploe in all Cypriniformes and Siluriformes species but not in Perciformes species. The mechanism for decreased Pcrit and Ploe in Cypriniformes and Siluriformes species is at least partially due to the downregulated metabolic demand and/or the maintenance of a high oxygen supply capacity while fasting. The present study found that the effect of fasting on hypoxia tolerance depends upon phylogeny in freshwater fish species. The information acquired in the present study is highly valuable in aquaculture industries and can be used for species conservation in the field.
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Ichthyophthirius multifiliis is a parasite that poses a considerable threat to aquaculture and the ornamental fish industry, but with limited effective treatment options available. This study employed RT-qPCR to detect and analyze the expression changes of partial toll-like receptor (TLR) genes (TLR1 and TLR21), adapter protein and signal transduction molecule genes (MyD88, TRIF, NF-κB, IRAK4, and IRF3), and cytokines (IL-6, IL-8, IL-13, CXC-α and CXCR1), as well as complement C3, in the skin, gill, fin, liver, head kidney and spleen of Rhinogobio ventralis under different infection conditions. Additionally, tissue sections and scanning electron microscopy were utilized to observe the pathological changes in the gills and fins of R. ventralis after infection with I. multifiliis. The expression patterns of TLR-related DEGs (differentially expressed genes) in diseased wild fish were analyzed, revealing upregulation of TLR1, TLR21, MyD88, NF-κB, IRAK4, TRIF, IRF3, IL-6, IL-8, IL-13, CXC-α, CXCR1, and C3 genes in various tissues, indicating that these genes may be involved in the immune response of R. ventralis to I. multifiliis infection. To further analyze the gene expression of sampled from the field, an artificial infection model of R. ventralis was established under laboratory conditions, with additional sampling from the skin and fins. These genes continued to show varying degrees of upregulation, but the results were not entirely consistent with those from Wudongde samples, which may be due to the more complex environment in the wild or differences in the degree of I. multifiliis infection in wild fish. The infection of I. multifiliis caused severe damage to the gills and fins of R. ventralis, characterized by extensive secretions on the gill and fin surfaces, with the presence of attached I. multifiliis trophonts, including damage and loss of gill filaments, swollen gill lamellae, and deformed gill plates, as well as cell proliferation and necrosis of gill epithelial cells. This study sheds light on the role of the TLR signaling pathway in resisting I. multifiliis infection and its associated histopathological changes in R. ventralis, providing valuable insights for the prevention and treatment of I. multifiliis infection in R. ventralis.
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Infecções por Cilióforos , Doenças dos Peixes , Proteínas de Peixes , Hymenostomatida , Imunidade Inata , Animais , Doenças dos Peixes/imunologia , Doenças dos Peixes/parasitologia , Hymenostomatida/fisiologia , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Infecções por Cilióforos/veterinária , Infecções por Cilióforos/imunologia , Imunidade Inata/genética , Perfilação da Expressão Gênica/veterinária , Receptores Toll-Like/genética , Receptores Toll-Like/imunologiaRESUMO
BACKGROUND: Age-related sarcopenia, characterized by reduced skeletal muscle mass and function, significantly affects the health of the elderly individuals. Oxidative stress plays a crucial role in the development of sarcopenia. Tripartite motif containing 16 (TRIM16) is implicated in orchestrating antioxidant responses to mitigate oxidative stress, yet its regulatory role in skeletal muscle remains unclear. This study aims to elucidate the impact of TRIM16 on enhancing antioxidant response through SIRT-1, consequently mitigating age-related oxidative stress, and ameliorating muscle atrophy. METHODS: Aged mouse models were established utilizing male mice at 18 months with D-galactose (D-gal, 200 mg/kg) intervention and at 24 months with natural aging, while 3-month-old young mice served as controls. Muscle cell senescence was induced in C2C12 myoblasts using 30 g/L D-gal. TRIM16 was overexpressed in the skeletal muscle of aged mice and silenced/overexpressed in C2C12 myoblasts. The effects of TRIM16 on skeletal muscle mass, grip strength, morphological changes, myotube formation, myogenic differentiation, and muscle atrophy indicators were evaluated. Reactive oxygen species (ROS) levels and oxidative stress-related parameters were measured. The SIRT-1 inhibitor EX-527 was employed to elucidate the protective role of TRIM16 mediated through SIRT-1. RESULTS: Aged mice displayed significant reductions in lean mass (-11.58%; -14.47% vs. young, P < 0.05), hindlimb lean mass (-17.38%; -15.95% vs. young, P < 0.05), and grip strength (-22.29%; -31.45% vs. young, P < 0.01). Skeletal muscle fibre cross-sectional area (CSA) decreased (-29.30%; -24.12% vs. young, P < 0.05). TRIM16 expression significantly decreased in aging skeletal muscle (-56.82%; -66.27% vs. young, P < 0.001) and senescent muscle cells (-46.53% vs. control, P < 0.001). ROS levels increased (+69.83% vs. control, P < 0.001), and myotube formation decreased in senescent muscle cells (-56.68% vs. control, P < 0.001). Expression of myogenic differentiation and antioxidant indicators decreased, while muscle atrophy markers increased in vivo and in vitro (all P < 0.05). Silencing TRIM16 in myoblasts induced oxidative stress and myotube atrophy, while TRIM16 overexpression partially mitigated aging effects on skeletal muscle. TRIM16 activation enhanced SIRT-1 expression (+75.38% vs. control, P < 0.001). SIRT-1 inhibitor EX-527 (100 µM) suppressed TRIM16's antioxidant response and mitigating muscle atrophy, offsetting the protective effect of TRIM16 on senescent muscle cells. CONCLUSIONS: This study elucidates TRIM16's role in mitigating oxidative stress and ameliorating muscle atrophy through the activation of SIRT-1-dependent antioxidant effects. TRIM16 emerges as a potential therapeutic target for age-related sarcopenia.