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A suspected outbreak of duck astrovirus (DAstV) disease occurred in a large Muscovy duck farm in Guangdong Province, China, in June 2022, which severely affected the production performance and health of Muscovy ducks. This study aimed to investigate the prevalence of DAstV disease in Southeast China. Herein, we employed semi-nested PCR ethodto screen 5203 swab and liver samples from 11 Muscovy duck farms in 5 provinces of China for the presence of DAstV. Among them, 1356 samples (26.06%, 1356/5203) tested positive for DAstV, out of which 11 DAstV strains were isolated after 10 generations of blind transmission through Leghorn male hepatoma (LMH) cells and performed their whole-genome sequencing. The alignment results showed that the 11 DAstV isolates exhibited relatively low homology (15.4%-75%) with the astrovirus isolates from other species published in GenBank, whereas their homology (nucleotide: 90.4%-99.99%; amino acid: 94%-99.8%) with the DAstV type 1 (DAstV-1) reference strain was higher, indicating considerable homology. The results indicated that DAstV-1 was the main pathogenic factor. Herein, we successfully recreated the clinical symptoms of natural infection in 28-day-old specific-pathogen-free (SPF) ducks using the DAstV-1-GDB-2022 strain. The primary clinical manifestations included liver enlargement, hemorrhaging, and disruptions in liver function. Additionally, we confirmed the cross-species transmission potential of DAstV-1, marking the first occurrence of clinical symptoms of DAstV in 28-day-old SPF chickens. Our findings provide new perspectives on the epidemiology and pathogenicity of DAstV-1 and may help in advancing the development of DAstV vaccines.
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OBJECTIVE: Medical adhesive-related skin injuries (MARSI), defined as skin damage associated with the use of medical adhesive products or devices, are a common and under-reported condition that compromises skin integrity. The prevention and management of MARSI that can occur around the needle insertion site of a chest wall implantable port in hospitalised patients with a tumour remain challenging issues. The aim of this study was to explore whether the incidence of MARSI could be reduced by changing the body position during dressing changes. METHOD: Participants were recruited between May 2019 and November 2020 in the oncology department of a tertiary hospital. Patients were randomly assigned to Group AB (supine followed by semi-recumbent position) and Group BA (semi-recumbent followed by supine position) with a standard intervening recovery interval of 21-28 days. Assessments for typical MARSI included itching, the combination of erythema and oedema, and blisters in the port area, and were graded according to the level of severity. RESULTS: The itch intensity was significantly lower in phase B (semi-recumbent) compared to phase A (supine) (2.35±1.985 versus 5.31±1.332, respectively; p<0.01). Similarly, the severity of erythema and oedema was less severe when comparing phase B to phase A: grade 0 (64.9% versus 10.5%, respectively); grade 1 (28.1% versus 19.3%, respectively); grade 2 (3.5% versus 7.0%, respectively); grade 3 (1.8% versus 45.6%, respectively); and grade 4 (1.8% versus 17.5%, respectively) (Z=5.703; p<0.01). Blisters were found far less frequently in phase B than phase A (1.8% versus 56.1%, respectively; p<0.01). CONCLUSION: The study provided statistically significant evidence that patients in a semi-recumbent position receiving dressing at a chest wall implantable port had fewer and less severe injection site MARSI than when in a supine position. DECLARATION OF INTEREST: The authors have no conflicts of interest to declare.
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Adesivos , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Incidência , Idoso , Adulto , Adesivos/efeitos adversos , Bandagens , Pele/lesões , Posicionamento do Paciente/efeitos adversos , PosturaRESUMO
Biomineralization is a natural process in which organisms regulate the growth of inorganic minerals to form biominerals with unique layered structures, such as bones and teeth, primarily composed of calcium and phosphorus. Tooth decay significantly impacts our daily lives, and the key to tooth regeneration lies in restoring teeth through biomimetic approaches, utilizing mineralization strategies or materials that mimic natural processes. This review delves into the types, properties, and transformations of calcium and phosphorus minerals, followed by an exploration of the mechanisms behind physiological and pathological mineralization in living organisms. It summarizes the mechanisms and commonalities of biomineralization and discusses the advancements in dental biomineralization research, guided by insights into calcium and phosphorus mineral biomineralization. This review concludes by addressing the current challenges and future directions in the field of dental biomimetic mineralization.
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Mesenchymal stem cells (MSCs) are recruited by malignant tumor cells to the tumor microenvironment (TME) and play a crucial role in the initiation and progression of malignant tumors. This role encompasses immune evasion, promotion of angiogenesis, stimulation of cancer cell proliferation, correlation with cancer stem cells, multilineage differentiation within the TME, and development of treatment resistance. Simultaneously, extensive research is exploring the homing effect of MSCs and MSC-derived extracellular vesicles (MSCs-EVs) in tumors, aiming to design them as carriers for antitumor substances. These substances are targeted to deliver antitumor drugs to enhance drug efficacy while reducing drug toxicity. This paper provides a review of the supportive role of MSCs in tumor progression and the associated molecular mechanisms. Additionally, we summarize the latest therapeutic strategies involving engineered MSCs and MSCs-EVs in cancer treatment, including their utilization as carriers for gene therapeutic agents, chemotherapeutics, and oncolytic viruses. We also discuss the distribution and clearance of MSCs and MSCs-EVs upon entry into the body to elucidate the potential of targeted therapies based on MSCs and MSCs-EVs in cancer treatment, along with the challenges they face.
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BACKGROUND: Artificial Intelligence(AI)-based solutions for Gleason grading hold promise for pathologists, while image quality inconsistency, continuous data integration needs, and limited generalizability hinder their adoption and scalability. METHODS: We present a comprehensive digital pathology workflow for AI-assisted Gleason grading. It incorporates A!MagQC (image quality control), A!HistoClouds (cloud-based annotation), Pathologist-AI Interaction (PAI) for continuous model improvement, Trained on Akoya-scanned images only, the model utilizes color augmentation and image appearance migration to address scanner variations. We evaluate it on Whole Slide Images (WSI) from another five scanners and conduct validations with pathologists to assess AI efficacy and PAI. RESULTS: Our model achieves an average F1 score of 0.80 on annotations and 0.71 Quadratic Weighted Kappa on WSIs for Akoya-scanned images. Applying our generalization solution increases the average F1 score for Gleason pattern detection from 0.73 to 0.88 on images from other scanners. The model accelerates Gleason scoring time by 43% while maintaining accuracy. Additionally, PAI improve annotation efficiency by 2.5 times and led to further improvements in model performance. CONCLUSIONS: This pipeline represents a notable advancement in AI-assisted Gleason grading for improved consistency, accuracy, and efficiency. Unlike previous methods limited by scanner specificity, our model achieves outstanding performance across diverse scanners. This improvement paves the way for its seamless integration into clinical workflows.
Gleason grading is a well-accepted diagnostic standard to assess the severity of prostate cancer in patients' tissue samples, based on how abnormal the cells in their prostate tumor look under a microscope. This process can be complex and time-consuming. We explore how artificial intelligence (AI) can help pathologists perform Gleason grading more efficiently and consistently. We build an AI-based system which automatically checks image quality, standardizes the appearance of images from different equipment, learns from pathologists' feedback, and constantly improves model performance. Testing shows that our approach achieves consistent results across different equipment and improves efficiency of the grading process. With further testing and implementation in the clinic, our approach could potentially improve prostate cancer diagnosis and management.
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OBJECTIVES: To build self-supervised foundation models for multicontrast MRI of the whole brain and evaluate their efficacy in assisting diagnosis of brain tumors. METHODS: In this retrospective study, foundation models were developed using 57,621 enhanced head MRI scans through self-supervised learning with a pretext task of cross-contrast context restoration with two different content dropout schemes. Downstream classifiers were constructed based on the pretrained foundation models and fine-tuned for brain tumor detection, discrimination, and molecular status prediction. Metrics including accuracy, sensitivity, specificity, and area under the ROC curve (AUC) were used to evaluate the performance. Convolutional neural networks trained exclusively on downstream task data were employed for comparative analysis. RESULTS: The pretrained foundation models demonstrated their ability to extract effective representations from multicontrast whole-brain volumes. The best classifiers, endowed with pretrained weights, showed remarkable performance with accuracies of 94.9, 92.3, and 80.4%, and corresponding AUC values of 0.981, 0.972, and 0.852 on independent test datasets in brain tumor detection, discrimination, and molecular status prediction, respectively. The classifiers with pretrained weights outperformed the convolutional classifiers trained from scratch by approximately 10% in terms of accuracy and AUC across all tasks. The saliency regions in the correctly predicted cases are mainly clustered around the tumors. Classifiers derived from the two dropout schemes differed significantly only in the detection of brain tumors. CONCLUSIONS: Foundation models obtained from self-supervised learning have demonstrated encouraging potential for scalability and interpretability in downstream brain tumor-related tasks and hold promise for extension to neurological diseases with diffusely distributed lesions. CLINICAL RELEVANCE STATEMENT: The application of our proposed method to the prediction of key molecular status in gliomas is expected to improve treatment planning and patient outcomes. Additionally, the foundation model we developed could serve as a cornerstone for advancing AI applications in the diagnosis of brain-related diseases.
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An outbreak of duck astrovirus (DAstV) has occurred in duck farming regions of China, causing substantial economic setbacks in the duck industry. This investigation aimed to examine the variations in DAstV pathogenicity among ducks at different age intervals. Infections were induced in ducks at distinct age groups (1, 7, 14, 21, and 28 d) utilizing the DAstv-1-GDB-2022 strain. The results indicate increased pathogenicity of the DAstv-1-GDB-2022 strain in ducklings aged 21 to 28 d, manifesting as liver and kidney enlargement, severe bleeding, and potential fatalities. Conversely, ducklings aged 1 and 14 d displayed milder symptoms postinfection. Notably, viral shedding continued in ducks of diverse age groups even 21 d postinfection (Dpi). Moreover, DAstV replicates in various tissues, predominantly affecting the liver. Immunohistochemical tests using rabbit anti-DAstV antibodies revealed robust positive signals in both the liver and kidneys, which correlated with the clinical symptom severity observed through macroscopic and microscopic examinations. Serum biochemical assays and indirect ELISA demonstrated a consistent response to DAstV infection across different age groups, with older ducklings exhibiting increased sensitivity. In conclusion, this study successfully replicated clinical symptoms similar to those of natural DAstV infection using the DAstv-1-GDB-2022 strain. Importantly, we systematically delineated the differences in susceptibility to DAstV among ducks at various ages, laying the foundation for further research into the pathogenic mechanisms of DAstV and potential vaccine development.
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Infecções por Astroviridae , Avastrovirus , Patos , Doenças das Aves Domésticas , Animais , Patos/virologia , Doenças das Aves Domésticas/virologia , Doenças das Aves Domésticas/patologia , Infecções por Astroviridae/veterinária , Infecções por Astroviridae/virologia , Avastrovirus/fisiologia , Fatores Etários , Suscetibilidade a Doenças/veterinária , Suscetibilidade a Doenças/virologia , China/epidemiologiaRESUMO
Prostate cancer (PC) develops in a microenvironment where the stromal cells modulate adjacent tumor growth and progression. Here, we demonstrated elevated levels of monoamine oxidase B (MAOB), a mitochondrial enzyme that degrades biogenic and dietary monoamines, in human PC stroma, which was associated with poor clinical outcomes of PC patients. Knockdown or overexpression of MAOB in human prostate stromal fibroblasts indicated that MAOB promotes cocultured PC cell proliferation, migration, and invasion and co-inoculated prostate tumor growth in mice. Mechanistically, MAOB induces a reactive stroma with activated marker expression, increased extracellular matrix remodeling, and acquisition of a protumorigenic phenotype through enhanced production of reactive oxygen species. Moreover, MAOB transcriptionally activates CXCL12 through Twist1 synergizing with TGFß1-dependent Smads in prostate stroma, which stimulates tumor-expressed CXCR4-Src/JNK signaling in a paracrine manner. Pharmacological inhibition of stromal MAOB restricted PC xenograft growth in mice. Collectively, these findings characterize the contribution of MAOB to PC and suggest MAOB as a potential stroma-based therapeutic target.
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Monoaminoxidase , Neoplasias da Próstata , Animais , Humanos , Masculino , Camundongos , Linhagem Celular Tumoral , Fibroblastos/metabolismo , Monoaminoxidase/genética , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Transdução de Sinais , Microambiente TumoralRESUMO
Riemerella anatipestifer (RA) causes epizootic infectious polyserositis in ducks with high mortality and leads to huge economic losses worldwide. Bacterial resistance poses a challenge for the control of the disease, vaccines failed to provide ideal cross-protection. Thus, the preparation of vaccines based on popular serotypes is important. In this study, we collected 700 brain and liver tissues of dead ducks from 8 provinces in southern China from 2016 to 2022 and obtained 195 RA isolates with serotypes 1, 2, 7, and 10. Serotypes 1 and 2 were the most prevalent (82%). A novel bivalent inactivated vaccine WZX-XT5 containing propolis adjuvant was prepared, we chose XT5 (serotype 1) and WZX (serotype 2) as vaccine strains and evaluated WZX-XT5-induced immune response and protective efficacy in ducks. Results showed that the XT5 (LD50, 3.5 × 103 CFU) exhibited high virulence and provided better protection against RA compared with ZXP, DCR and LCF1 (LD50, 108 CFU). Notably, the dose of 109 CFU provided ideal protection compared with 108 CFU, propolis and oil emulsion adjuvants induced stronger protective efficacy compared with aluminum hydroxide adjuvant. Importantly, WZX-XT5 immunization induced high levels of RA-specific IgY, IFN-γ, IL-2, and IL-4 in serum and offered over 90% protection against RA with ultra-high lethal dose in ducks. Additionally, no clinical signs of RA infection or obvious pathological damage in tissues were observed in protected ducks. Overall, this study first reports the identification, serotyping and virulence of RA in ducks of southern China and the preparation of a novel bivalent inactivated vaccine, providing useful scientific information to prevent and control RA infection.
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Infecções por Flavobacteriaceae , Doenças das Aves Domésticas , Própole , Riemerella , Animais , Patos/microbiologia , Sorogrupo , Doenças das Aves Domésticas/microbiologia , Infecções por Flavobacteriaceae/prevenção & controle , Infecções por Flavobacteriaceae/veterinária , Vacinas Combinadas , Galinhas , Adjuvantes Imunológicos/farmacologia , Vacinas de Produtos InativadosRESUMO
Ambrosia trifida (giant ragweed) is an invasive plant that can cause serious damage to natural ecosystems and severe respiratory allergies. However, the genomic basis of invasive adaptation and pollen allergens in Ambrosia species remain largely unknown. Here, we present a 1.66 Gb chromosome-scale reference genome for giant ragweed and identified multiple types of genome duplications, which are responsible for its rapid environmental adaptation and pollen development. The largest copies number and species-specific expansions of resistance-related gene families compared to Heliantheae alliance might contribute to resist stresses, pathogens and rapid adaptation. To extend the knowledge of evolutionary process of allergic pollen proteins, we predicted 26 and 168 potential pollen allergen candidates for giant ragweed and other Asteraceae plant species by combining machine learning and identity screening. Interestingly, we observed a specific tandemly repeated array for potential allergenic pectate lyases among Ambrosia species. Rapid evolutionary rates on putative pectate lyase allergens may imply a crucial role of nonsynonymous mutations on amino acid residues for plant biological function and allergenicity. Altogether, this study provides insight into the molecular ecological adaptation and putative pollen allergens prediction that will be helpful in promoting invasion genomic research and evolution of putative pollen allergy in giant ragweed.
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Ambrosia , Hipersensibilidade , Ambrosia/genética , Antígenos de Plantas/genética , Ecossistema , Alérgenos/genética , Alérgenos/química , Pólen/genética , CromossomosRESUMO
Neutrophils play a critical role in the immune response to infection and tissue injury. However, recent studies have shown that neutrophils are a heterogeneous population with distinct subtypes that differ in their functional properties. Moreover, aging can alter neutrophil function and exacerbate immune dysregulation. In this review, we discuss the concept of neutrophil heterogeneity and how it may be affected by aging. We then examine the implications of neutrophil heterogeneity and aging for COVID-19 pathogenesis and wound healing. Specifically, we summarize the evidence for neutrophil involvement in COVID-19 and the potential mechanisms underlying neutrophil recruitment and activation in this disease. We also review the literature on the role of neutrophils in the wound healing process and how aging and neutrophil heterogeneity may impact wound healing outcomes. Finally, we discuss the potential for neutrophil-targeted therapies to improve clinical outcomes in COVID-19 and wound healing.
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COVID-19 , Neutrófilos , Humanos , COVID-19/patologia , Cicatrização , Envelhecimento , Infiltração de NeutrófilosRESUMO
In 2022, a global outbreak of Mpox (formerly monkeypox) occurred in various countries across Europe and America and rapidly spread to more than 100 countries and regions. The World Health Organization declared the outbreak to be a public health emergency of international concern due to the rapid spread of the Mpox virus. Consequently, nations intensified their efforts to explore treatment strategies aimed at combating the infection and its dissemination. Nevertheless, the available therapeutic options for Mpox virus infection remain limited. So far, only a few numbers of antiviral compounds have been approved by regulatory authorities. Given the high mutability of the Mpox virus, certain mutant strains have shown resistance to existing pharmaceutical interventions. This highlights the urgent need to develop novel antiviral drugs that can combat both drug resistance and the potential threat of bioterrorism. Currently, there is a lack of comprehensive literature on the pathophysiology and treatment of Mpox. To address this issue, we conducted a review covering the physiological and pathological processes of Mpox infection, summarizing the latest progress of anti-Mpox drugs. Our analysis encompasses approved drugs currently employed in clinical settings, as well as newly identified small-molecule compounds and antibody drugs displaying potential antiviral efficacy against Mpox. Furthermore, we have gained valuable insights from the process of Mpox drug development, including strategies for repurposing drugs, the discovery of drug targets driven by artificial intelligence, and preclinical drug development. The purpose of this review is to provide readers with a comprehensive overview of the current knowledge on Mpox.
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Inteligência Artificial , Mpox , Humanos , Mpox/tratamento farmacológico , Mpox/epidemiologia , Mpox/prevenção & controle , Anticorpos , Surtos de Doenças , Antivirais/farmacologia , Antivirais/uso terapêuticoRESUMO
As an enteric virus, chicken astrovirus has been related to various kinds of diseases in chickens, including white chick syndrome, runting-stunting syndrome, severe kidney disease, urate deposits and visceral gout, generating economic losses in the poultry industry globally. The complete ORF2 gene of 31 CAstV isolates in six provinces of China during 2020-2022 was characterized and analyzed with the purpose of better understanding the molecular epidemiology and genetic diversity of CAstV field isolates. Phylogenetic analysis which was based on the complete ORF2 (capsid) amino acid sequence of 31 CAstV isolates and 57 reference strains indicated that 2 isolates belonged to subgroup Ai, 10 isolates belonged to subgroup Bi, 3 isolates belonged to subgroup Bii, 5 isolates belonged to subgroup Biii, 7 isolates belonged to subgroup Biv, 3 isolates belonged to subgroup Bv, and one isolate (JS202103) belonged to a new B subgroup. In addition, the novel CAstV strain JS202103 was successfully isolated in vitro, and its whole genome shared 76.9-94.3% identity with the 29 CAstV reference strains. JS202103 caused hatchability reduction, dead embryos, kidney disease and visceral gout in chicken embryos. Moreover, this is the also the initial study focusing on diverse CAstV strains including subgroups Biii, Biv, and Bv circulate in China. The current work contributes to improving our understanding of CAstV isolates in China, and it will also provide references for developing efficient measures to control this virus.
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Background: Patients with rheumatic diseases have an increased likelihood of being admitted to the intensive care unit (ICU), highlighting the importance of promptly identifying high-risk individuals to enhance prognosis. This study aimed to assess the correlation of red blood cell distribution width to albumin ratio (RAR) with the 90-days and 360-days survival rates among critically ill rheumatic patients. Methods: Adult rheumatic patients admitted to the ICU from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database were included. The participants were categorized into two groups, survivors (n = 436) and non-survivors (n = 192), based on their 90-days survival outcome. The population was further classified into tertiles using RAR values, with RAR < 4.63 (n = 208), 4.63-6.07 (n = 211), and > 6.07 (n = 209). Kaplan-Meier curves were utilized to evaluate the cumulative survival rates at 90-days and 360-days. The association between RAR and mortality was assessed using restricted cubic splines (RCS) and multivariate Cox regression analysis. Additional subgroup analyses and sensitivity analyses were conducted to further explore the findings. Receiver operating characteristic (ROC) curves were generated to evaluate the predictive performance of RAR. Results: This study involved 628 critically ill patients with rheumatic diseases, and they had an all-cause mortality of 30.57% at 90-days and 38.69% at 360-days. Kaplan-Meier analysis showed a gradual decrease in both 90-days and 360-days cumulative survival with increasing RAR (χ2 = 24.400, p < 0.001; χ2 = 35.360, p < 0.001). RCS revealed that RAR was linearly related to 90-days and 360-days all-cause mortality risk for critically ill patients with rheumatic diseases (χ2 = 4.360, p = 0.225; χ2 = 1.900, p = 0.594). Cox regression analysis indicated that elevated RAR (> 6.07) was significantly correlated with mortality. The ROC curves demonstrated that an optimal cut-off value of RAR for predicting 90-days mortality was determined to be 5.453, yielding a sensitivity of 61.5% and specificity of 60.3%. Conclusion: Elevated RAR (> 6.07) was associated with all-cause mortality at 90-days and 360-days among critically ill patients with rheumatic diseases, serving as an independent risk factor for unfavorable prognosis.
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Assessing motor competence is essential for evaluating the effectiveness of physical activity interventions that aim to maintain or improve older adults' function. However, assessing motor competence in older adults who have difficulties walking or standing is challenging, because few instruments or guidelines are appropriate for these frail older adults. This article aims to describe challenges in evaluating motor function among frail older adults, discuss strategies for adapting motor function assessments to their home settings, and provide recommendations for future clinical trials so that older adults with ambulatory difficulties can benefit from motor function assessment and physical activity programs. Data came from the baseline assessment of 116 participants of an ongoing clinical trial, "Promoting Seniors' Health with Home Care Aides (Pro-Home)". Our results demonstrated that the Pro-Home study involved participants who would be typically excluded from clinical trials and that the two instruments selected or developed for Pro-Home (Short Physical Performance Battery, Pro-Home Ankle Range of Motion Measure) captured a wide range of lower extremity motor competence with no or few missing data. Recommendations for future studies include knowing the target population thoroughly, developing trust and rapport with all parties involved, and continuously collaborating with interviewers who conduct assessments.
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Exercício Físico , Idoso Fragilizado , Humanos , Idoso , CaminhadaRESUMO
BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer and is notorious for its resistance to both chemotherapy and small-molecule inhibitor targeted therapies. Subcellular targeted cancer therapy may thwart the resistance to produce a substantial effect. METHODS: We tested whether the resistance can be circumvented by subcellular targeted cancer therapy with DZ-CIS, which is a chemical conjugate of the tumor-cell specific heptamethine carbocyanine dye (HMCD) with cisplatin (CIS), a chemotherapeutic drug with limited use in ccRCC treatment because of frequent renal toxicity. RESULTS: DZ-CIS displayed cytocidal effects on Caki-1, 786-O, ACHN, and SN12C human ccRCC cell lines and mouse Renca cells in a dose-dependent manner and inhibited ACHN and Renca tumor formation in experimental mouse models. Noticeably, in tumor-bearing mice, repeated DZ-CIS use did not cause renal toxicity, in contrast to the CIS-treated control animals. In ccRCC tumors, DZ-CIS treatment inhibited proliferation markers but induced cell death marker levels. In addition, DZ-CIS at half maximal inhibitory concentration (IC50) sensitized Caki-1 cells to small-molecule mTOR inhibitors. Mechanistically, DZ-CIS selectively accumulated in ccRCC cells' subcellular organelles, where it damages the structure and function of mitochondria, leading to cytochrome C release, caspase activation, and apoptotic cancer cell death. CONCLUSIONS: Results from this study strongly suggest DZ-CIS be tested as a safe and effective subcellular targeted cancer therapy.
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Carcinoma de Células Renais , Neoplasias Renais , Humanos , Animais , Camundongos , Carcinoma de Células Renais/patologia , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Neoplasias Renais/patologia , Apoptose , Morte Celular , Linhagem Celular Tumoral , Proliferação de CélulasRESUMO
Glucocorticoids (GCs) are the important stress hormones and widely prescribed as drugs. Although stress has been suggested as a promoter of tumor progression, the direct influence of GCs on metastasis of tumor is not fully understood. Metastasis is a major cause of death in pancreatic cancer patients. In the present study, we investigated the effect of GCs on progression of pancreatic cancer and elucidated the underlying mechanism. It was found that GCs significantly promote cell adhesion, migration, and invasion of pancreatic cancer cells in vitro and their lung metastasis in vivo. Further mechanistic studies showed that GCs notably up-regulate the expression of a trans-membrane glycoprotein, mucin 1 (MUC1) and increase the activation of AKT. Inhibiting MUC1 expression not only attenuates the activation of AKT, but also significantly reduces the promoting effects of GCs on cell adhesion, migration, invasion, and lung metastasis of pancreatic cancer cells. Moreover, GCs not only significantly up-regulate expression of Rho-associated kinase 1/2 (ROCK1/2) and matrix metalloproteinase 3 and 7 (MMP3/7), but also activate ROCK2, which are also involved in the pro-migratory and pro-invasive effects of GCs in pancreatic cancer cells. Taken together, our findings reveal that GCs promote metastasis of pancreatic cancer cells through complex mechanism. MUC1-PI3K/AKT pathway, ROCK1/2 and MMP3/7 are involved in the promoting effect of GCs on cell migration, invasion and metastasis in pancreatic cancer cells. These results suggest the importance of reducing stress and GCs administration in patients with pancreatic cancer to avoid an increased risk of cancer metastasis.
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Adesão Celular , Movimento Celular , Glucocorticoides , Neoplasias Pulmonares , Invasividade Neoplásica , Metástase Neoplásica , Neoplasias Pancreáticas , Glucocorticoides/farmacologia , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pancreáticas/patologia , Adesão Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Invasividade Neoplásica/patologia , Quinases Associadas a rho/efeitos dos fármacos , Quinases Associadas a rho/metabolismo , Metaloproteinase 3 da Matriz/efeitos dos fármacos , Metaloproteinase 3 da Matriz/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismoRESUMO
As an important genomic marker for oligodendrogliomas, early determination of 1p/19q co-deletion status is critical for guiding therapy and predicting prognosis in patients with glioma. The purpose of this study is to systematically review the literature concerning the magnetic resonance imaging (MRI) with artificial intelligence (AI) methods for predicting 1p/19q co-deletion status in glioma. PubMed, Scopus, Embase, and IEEE Xplore were searched in accordance with the Preferred Reporting Items for systematic reviews and meta-analyses guidelines. Methodological quality of studies was assessed according to the Quality Assessment of Diagnostic Accuracy Studies-2. Finally, 28 studies were included in the quantitative analysis. Diagnostic test accuracy reached an area under the ROC curve of 0.71-0.98 were reported in 24 studies. The remaining four studies with no available AUC provided an accuracy of 0.75-0. 89. The included studies varied widely in terms of imaging sequences, input features, and modeling methods. The current review highlighted that integrating MRI with AI technology is a potential tool for determination 1p/19q status pre-operatively and noninvasively, which can possibly help clinical decision-making. However, the reliability and feasibility of this approach still need to be further validated and improved in a real clinical setting. EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: 2.
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Neoplasias Encefálicas , Glioma , Oligodendroglioma , Humanos , Inteligência Artificial , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Reprodutibilidade dos Testes , Deleção Cromossômica , Glioma/diagnóstico por imagem , Glioma/genética , Glioma/patologia , Isocitrato Desidrogenase/genética , MutaçãoRESUMO
Goose astroviruses (GoAstV) cause fatal gout and decrease product performance in the waterfowl industry across the world. Since no effective vaccines are available, studies on the epidemiology of the virus are necessary for vaccine development. In this study, we collected 94 gout samples from goose farms in the Guangdong Province of South China. Among them, 87 samples (92.6%) tested positive for GoAstV, out of which five GoAstV strains were isolated after four generations of blind transmission through healthy 13-day-old goose embryos. The whole genome of the isolates was sequenced and further analyzed by comparing the sequences with published sequences from China and other parts of the world. The results of the alignment analysis showed that nucleotide sequence similarities among the five GoAstV isolates were around 97.4-98.8%, 98.6-100%, 98.1-99.8%, and 96.7-100% for the whole genome, ORF1a, ORF1b, and ORF2, respectively. These results showed that the GoAstV isolates were highly similar to each other, although they were prevalent in five different regions of the Guangdong Province. The results of the phylogenetic analysis showed that the whole genome, along with the ORF1a, ORF1b, and ORF2 genes of the isolates, were clustered on a single branch, along with the recently published GoAstV-2, and were very distinct from the DNA sequences of the GoAstV-1 virus. In this study, we also reproduced the clinical symptoms of natural infection using the GoAstV-GD2101 isolates, confirming that the gout-causing pathogen in goslings was the goose astrovirus. These findings provided new insights into the pathogenicity and genetic evolution of GoAstV and laid the foundation for effectively controlling the disease.
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The pandemic of COVID-19 creates an imperative need for sensitive and portable detection of SARS-CoV-2. We devised a SERS-read, CRISPR/Cas-powered nanobioassay, termed as OVER-SARS-CoV-2 (One-Vessel Enhanced RNA test on SARS-CoV-2), which enabled supersensitive, ultrafast, accurate and portable detection of SARS-CoV-2 in a single vessel in an amplification-free and anti-interference manner. The SERS nanoprobes were constructed by conjugating gold nanoparticles with Raman reporting molecular and single-stranded DNA (ssDNA) probes, whose aggregation-to-dispersion changes can be finely tuned by target-activated Cas12a though trans-cleavage of linker ssDNA. As such, the nucleic acid signals could be dexterously converted and amplified to SERS signals. By customizing an ingenious vessel, the steps of RNA reverse transcription, Cas12a trans-cleavage and SERS nanoprobes crosslinking can be integrated into a single and disposal vessel. It was proved that our proposed nanobioassay was able to detect SARS-CoV-2 as low as 200 copies/mL without any pre-amplification within 45 min. In addition, the proposed nanobioassay was confirmed by clinical swab samples and challenged for SARS-CoV-2 detection in simulated complex environmental and food samples. This work enriches the arsenal of CRISPR-based diagnostics (CRISPR-Dx) and provides a novel and robust platform for SARS-CoV-2 decentralized detection, which can be put into practice in the near future.