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1.
Nat Immunol ; 25(2): 268-281, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38195702

RESUMO

Melanoma cells, deriving from neuroectodermal melanocytes, may exploit the nervous system's immune privilege for growth. Here we show that nerve growth factor (NGF) has both melanoma cell intrinsic and extrinsic immunosuppressive functions. Autocrine NGF engages tropomyosin receptor kinase A (TrkA) on melanoma cells to desensitize interferon γ signaling, leading to T and natural killer cell exclusion. In effector T cells that upregulate surface TrkA expression upon T cell receptor activation, paracrine NGF dampens T cell receptor signaling and effector function. Inhibiting NGF, either through genetic modification or with the tropomyosin receptor kinase inhibitor larotrectinib, renders melanomas susceptible to immune checkpoint blockade therapy and fosters long-term immunity by activating memory T cells with low affinity. These results identify the NGF-TrkA axis as an important suppressor of anti-tumor immunity and suggest larotrectinib might be repurposed for immune sensitization. Moreover, by enlisting low-affinity T cells, anti-NGF reduces acquired resistance to immune checkpoint blockade and prevents melanoma recurrence.


Assuntos
Melanoma , Receptor de Fator de Crescimento Neural , Humanos , Receptor de Fator de Crescimento Neural/genética , Receptor de Fator de Crescimento Neural/metabolismo , Fator de Crescimento Neural/genética , Fator de Crescimento Neural/metabolismo , Tropomiosina , Melanoma/terapia , Receptor trkA/genética , Receptor trkA/metabolismo , Citoproteção , Inibidores de Checkpoint Imunológico , Células T de Memória , Terapia de Imunossupressão , Imunoterapia , Receptores de Antígenos de Linfócitos T
2.
Cell ; 162(4): 900-10, 2015 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-26276636

RESUMO

CTCF and the associated cohesin complex play a central role in insulator function and higher-order chromatin organization of mammalian genomes. Recent studies identified a correlation between the orientation of CTCF-binding sites (CBSs) and chromatin loops. To test the functional significance of this observation, we combined CRISPR/Cas9-based genomic-DNA-fragment editing with chromosome-conformation-capture experiments to show that the location and relative orientations of CBSs determine the specificity of long-range chromatin looping in mammalian genomes, using protocadherin (Pcdh) and ß-globin as model genes. Inversion of CBS elements within the Pcdh enhancer reconfigures the topology of chromatin loops between the distal enhancer and target promoters and alters gene-expression patterns. Thus, although enhancers can function in an orientation-independent manner in reporter assays, in the native chromosome context, the orientation of at least some enhancers carrying CBSs can determine both the architecture of topological chromatin domains and enhancer/promoter specificity. These findings reveal how 3D chromosome architecture can be encoded by linear genome sequences.


Assuntos
Cromossomos/metabolismo , Técnicas Genéticas , Proteínas Repressoras/metabolismo , Animais , Sítios de Ligação , Fator de Ligação a CCCTC , Caderinas/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas Cromossômicas não Histona/metabolismo , Cromossomos/química , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , DNA/química , Elementos Facilitadores Genéticos , Expressão Gênica , Genoma Humano , Humanos , Células K562 , Camundongos , Regiões Promotoras Genéticas , Globinas beta/genética , Coesinas
3.
PLoS Biol ; 19(12): e3001498, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34936658

RESUMO

The human gut symbiont Ruminococcus gnavus displays strain-specific repertoires of glycoside hydrolases (GHs) contributing to its spatial location in the gut. Sequence similarity network analysis identified strain-specific differences in blood-group endo-ß-1,4-galactosidase belonging to the GH98 family. We determined the substrate and linkage specificities of GH98 from R. gnavus ATCC 29149, RgGH98, against a range of defined oligosaccharides and glycoconjugates including mucin. We showed by HPAEC-PAD and LC-FD-MS/MS that RgGH98 is specific for blood group A tetrasaccharide type II (BgA II). Isothermal titration calorimetry (ITC) and saturation transfer difference (STD) NMR confirmed RgGH98 affinity for blood group A over blood group B and H antigens. The molecular basis of RgGH98 strict specificity was further investigated using a combination of glycan microarrays, site-directed mutagenesis, and X-ray crystallography. The crystal structures of RgGH98 in complex with BgA trisaccharide (BgAtri) and of RgGH98 E411A with BgA II revealed a dedicated hydrogen network of residues, which were shown by site-directed mutagenesis to be critical to the recognition of the BgA epitope. We demonstrated experimentally that RgGH98 is part of an operon of 10 genes that is overexpresssed in vitro when R. gnavus ATCC 29149 is grown on mucin as sole carbon source as shown by RNAseq analysis and RT-qPCR confirmed RgGH98 expression on BgA II growth. Using MALDI-ToF MS, we showed that RgGH98 releases BgAtri from mucin and that pretreatment of mucin with RgGH98 confered R. gnavus E1 the ability to grow, by enabling the E1 strain to metabolise BgAtri and access the underlying mucin glycan chain. These data further support that the GH repertoire of R. gnavus strains enable them to colonise different nutritional niches in the human gut and has potential applications in diagnostic and therapeutics against infection.


Assuntos
Clostridiales/metabolismo , Mucina-1/metabolismo , Sistema ABO de Grupos Sanguíneos/imunologia , Antígenos de Grupos Sanguíneos/imunologia , Clostridiales/genética , Clostridiales/fisiologia , Microbioma Gastrointestinal , Trato Gastrointestinal , Glicosídeo Hidrolases/metabolismo , Humanos , Mucinas/metabolismo , Oligossacarídeos/metabolismo , Polissacarídeos/metabolismo , Ruminococcus/genética , Ruminococcus/metabolismo , Especificidade por Substrato , Espectrometria de Massas em Tandem/métodos
4.
Arch Microbiol ; 206(5): 222, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38642140

RESUMO

Animal feed is vulnerable to fungal infections, and the use of bio-preserving probiotics has received increasing attention. In contrast to Lactobacillus and Bifidobacteria spp., fewer Bacillus spp. have been recognized as antifungal probiotics. Therefore, our objective was to screen antifungal strains and provide more Bacillus candidates to bridge this gap. Here, we screened 56 bacterial strains for cyclic lipopeptide genes and conducted an antifungal assay with Aspergillus niger as a representative fungus. We found that a Bacillus strain Bacillus amyloliquefaciens PM415, isolated from pigeon manure, exhibited the highest fungal inhibition activity as demonstrated by the confrontation assay and morphological observation under scanning electron microscope (SEM). Preliminary safety assessment and probiotic characterization revealed its non-pathogenic feature and stress tolerance capability. Whole genome sequencing of Bacillus amyloliquefaciens PM415 revealed a genome size of 4.16 Mbp and 84 housekeeping genes thereof were used for phylogenetic analysis showing that it is most closely related to Bacillus amyloliquefaciens LFB112. The in silico analysis further supported its non-pathogenic feature at the genomic level and revealed potential biosynthetic gene clusters responsible for its antifungal property. RNA-seq analysis revealed genome-wide changes in transportation, amino acid metabolism, non-ribosomal peptides (NRPs) biosynthesis and glycan degradation during fungal antagonism. Our results suggest that Bacillus amyloliquefaciens PM415 is a safe and effective probiotic strain that can prevent fungal growth in animal feeds.


Assuntos
Bacillus amyloliquefaciens , Bacillus , Probióticos , Animais , Bacillus amyloliquefaciens/química , Antifúngicos/farmacologia , Antifúngicos/metabolismo , Filogenia
5.
Nutr J ; 23(1): 62, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38862996

RESUMO

INTRODUCTION: The Weight-Adjusted Waist Index (WWI) is a new indicator of obesity that is associated with all-cause mortality in Asian populations. Our study aimed to investigate the linear and non-linear associations between WWI and all-cause mortality in non-Asian populations in the United States, and whether WWI was superior to traditional obesity indicators as a predictor of all-cause mortality. METHODS: We conducted a cohort study using data from the 2011-2018 National Health and Nutrition Examination Survey (NHANES), involving 18,592 participants. We utilized Cox proportional hazard models to assess the association between WWI, BMI, WC, and the risk of all-cause mortality, and performed subgroup analyses and interaction tests. We also employed a receiver operating characteristics (ROC) curve study to evaluate the effectiveness of WWI, BMI, and WC in predicting all-cause mortality. RESULTS: After adjusting for confounders, WWI, BMI, and WC were positively associated with all-cause mortality. The performance of WWI, BMI, and WC in predicting all-cause mortality yielded AUCs of 0.697, 0.524, and 0.562, respectively. The data also revealed a U-shaped relationship between WWI and all-cause mortality. Race and cancer modified the relationship between WWI and all-cause mortality, with the relationship being negatively correlated in African Americans and cancer patients. CONCLUSIONS: In non-Asian populations in the United States, there is a U-shaped relationship between WWI and all-cause mortality, and WWI outperforms BMI and WC as a predictor of all-cause mortality. These findings may contribute to a better understanding and prediction of the relationship between obesity and mortality, and provide support for effective obesity management strategies.


Assuntos
Índice de Massa Corporal , Inquéritos Nutricionais , Obesidade , Circunferência da Cintura , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Inquéritos Nutricionais/métodos , Inquéritos Nutricionais/estatística & dados numéricos , Estudos de Coortes , Estados Unidos/epidemiologia , Adulto , Obesidade/mortalidade , Mortalidade , Idoso , Peso Corporal , Fatores de Risco , Causas de Morte , Modelos de Riscos Proporcionais
6.
Artigo em Inglês | MEDLINE | ID: mdl-38330585

RESUMO

Objective: This study aims to compare the efficacy of ureteroscopy with holmium laser lithotripsy and extracorporeal shock wave lithotripsy (ESWL) in treating ureteral calculus (UC). Methods: We enrolled 86 patients with UC treated in our urology department from November 2020 to November 2022. Group A (n=43) underwent ureteroscopic holmium laser lithotripsy, while Group B (n=43) received ESWL. We recorded treatment duration, post-treatment hematuria duration, and post-treatment stone clearance rates. Renal function and stress response were assessed before and 3 days after treatment. Post-treatment complications were documented, and patient quality of life was evaluated using the SF-36 health questionnaire. Results: Group A exhibited significantly shorter treatment and post-treatment hematuria durations compared to Group B (P < .05). In stones >1 cm, group A demonstrated a higher clearance rate (P < .05). Post-treatment, Group A showed improved renal function and lower stress response (P < .05). The incidence of post-treatment complications did not differ significantly between groups (P > .05), but SF-36 scores were higher in Group A (P < .05). Conclusions: Ureteroscopy with holmium laser lithotripsy proves effective in UC treatment, contributing to a shortened recovery period and enhanced patient quality of life.

7.
Angew Chem Int Ed Engl ; : e202319661, 2024 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-38703353

RESUMO

Constructing artificial solid electrolyte interface on the Zn anode surface is recognized as an appealing method to inhibit zinc dendrites and side reactions, whereas the current techniques are complex and time-consuming. Here, a robust and zincophilic zinc tungstate (ZnWO4) layer has been in situ constructed on the Zn anode surface (denoted as ZWO@Zn) by an ultrafast chemical solution reaction. Comprehensive characterizations and theoretical calculations demonstrate that the ZWO layer can effectively modulate the interfacial electric field distribution and promote the Zn2+ uniform diffusion, thus facilitating the uniform Zn2+ nucleation and suppressing zinc dendrites. Besides, ZWO layer can prevent direct contact between the Zn/water and increase the hydrogen evolution reaction overpotential to eliminate side reactions. Consequently, the in situ constructed ZWO layer facilitates remarkable reversibility in the ZWO@Zn||Ti battery, achieving an impressive Coulombic efficiency of 99.36 % under 1.0 mA cm-2, unprecedented cycling lifespan exceeding 1800 h under 1.0 mA cm-2 in ZWO@Zn||ZWO@Zn battery, and a steady and reliable operation of the overall ZWO@Zn||VS2 battery. The work provides a simple, low cost, and ultrafast pathway to crafting protective layers for driving advancements in aqueous zinc-metal batteries.

8.
Small ; 19(48): e2304367, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37566780

RESUMO

Since the linkages structured in covalent organic frameworks (COFs) usually impact the charge transfer behavior during photocatalytic hydrogen evolution reaction (pc-HER), linkage dependence on charge transfer kinetics should be further claimed. Herein, COFs with N-based linkages and pyrene-based building nodes are constructed to enable us to obtain new clues about the charge transfer behavior and evolution tendency relevant to linkages at a molecular level for pc-HER. It is demonstrated that photo-excited electrons preferably move to the N sites in C=N linkage for pc-HER and are trapped around NN linkage as well. A high electron transfer rate does not point to high photocatalytic activity directly, while a small difference between the electron transfer rate and electron recombination rate ΔkCT - CR predicts the inefficiency of charge transfer in Azod-COFs. Contrarily, large value of ΔkCT - CR in the case of Benzd-COFs, demonstrats an unimpeded charge transfer process to result in boosted pc-HER rate (2027.3 µmol h-1 g-1 ). This work offers a prominent strategy for the reasonable design of efficient photocatalysts at the molecular level for structural regulation and achieves an efficient charge transfer process for the pc-HER process.

9.
Brief Bioinform ; 22(5)2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34370020

RESUMO

Recent advances in bioinformatics analyses have led to the development of novel tools enabling the capture and trajectory mapping of single-cell RNA sequencing (scRNAseq) data. However, there is a lack of methods to assess the contributions of biological pathways and transcription factors to an overall developmental trajectory mapped from scRNAseq data. In this manuscript, we present a simplified approach for trajectory inference of pathway significance (TIPS) that leverages existing knowledgebases of functional pathways and other gene lists to provide further mechanistic insights into a biological process. TIPS identifies key pathways which contribute to a process of interest, as well as the individual genes that best reflect these changes. TIPS also provides insight into the relative timing of pathway changes, as well as a suite of visualizations to enable simplified data interpretation of scRNAseq libraries generated using a wide range of techniques. The TIPS package can be run through either a web server or downloaded as a user-friendly GUI run in R, and may serve as a useful tool to help biologists perform deeper functional analyses and visualization of their single-cell data.


Assuntos
Biologia Computacional/métodos , Perfilação da Expressão Gênica/métodos , RNA-Seq/métodos , Transdução de Sinais/genética , Análise de Célula Única/métodos , Linfócitos T CD8-Positivos/metabolismo , Células Cultivadas , Humanos , Internet , Reprodutibilidade dos Testes , Fatores de Tempo
10.
BMC Endocr Disord ; 23(1): 162, 2023 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-37537589

RESUMO

BACKGROUND: The weight-adjusted waist circumference index (WWI) is a novel obesity indicator that offers improved accuracy in assessing both muscle and fat mass compared to traditional measures. This study aimed to investigate the association between WWI and bone mineral density (BMD) in adults. METHODS: Weighted multivariate logistic regression, subgroup analysis, interaction tests and restricted cubic spline (RCS) curves were used to explore the relationship between WWI and BMD based on data from the National Health and Nutrition Examination Survey (NHANES). RESULTS: This study had 40,568 individuals in total. At all four measurement sites, we detected a negative linear correlation between WWI and BMD. Even when quartile factors for WWI were created, this unfavorable connection maintained. In comparison to those in the lowest quartile, those in the highest percentile of WWI showed declines in lumbar BMD of 0.08 g/cm2 and femoral neck BMD of 0.03 g/cm2, respectively. This adverse correlation, nevertheless, differed among several categories. CONCLUSIONS: Our findings suggest an adverse correlation between WWI and BMD among US adults. Employing WWI as a tool for osteoporosis prevention in the general population may enhance interventions.


Assuntos
Densidade Óssea , Obesidade , Adulto , Humanos , Densidade Óssea/fisiologia , Inquéritos Nutricionais , Obesidade/diagnóstico , Circunferência da Cintura , Absorciometria de Fóton/métodos
11.
BMC Cardiovasc Disord ; 23(1): 591, 2023 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-38036972

RESUMO

BACKGROUND: Coronary chronic total occlusion (CTO) interventions are more complex than general percutaneous coronary intervention (PCI) procedures. However, only a few nursing methods are specifically applied to patients undergoing CTO interventions. And the conventional nursing effect is not ideal, urgent need to explore more effective nursing methods. The checklist is a simple and effective tool for error management and performance improvement that has been widely used in many fields. But there have been no reports of the checklist being used to improve care for CTO patients. OBJECTIVE: This study aimed to investigate the effectiveness of a checklist-based nursing care process in patients undergoing Coronary chronic total occlusion (CTO) interventions, including duration of care, patient anxiety, improved patient satisfaction, and occurrence of adverse events. METHODS: A total of 120 CTO patients undergoing percutaneous coronary intervention (PCI) were selected at our hospital and divided into an intervention group (n = 60, adopted the checklist-based nursing care process for patient care) and a control group (n = 60, adopted nursing care according to the existing workflow) according to different nursing interventions. After surgery, the nurse in charge of the patient completed the nursing according to the "List of postoperative care for CTO patients" filled in by the patient within 24 h after surgery, conducted a doctor satisfaction survey, recorded adverse events, and completed the postoperative Self-Rating Anxiety Scale (SAS) score and patient satisfaction survey before the patient was discharged. Subsequently, the Qc team checks the completion of the patient's checklist for safety and the completion of the questionnaire. Finally, the differences between the two groups in preoperative nursing time, incidence of adverse events caused by nurses' omission or inadequate guidance, patient anxiety, and doctor and patient satisfaction were compared. RESULTS: The intervention grouphad significantly shorter preoperative nursing care time and significantly lower the total number of adverse events than the control group (P < 0.05).The postoperative Self-Rating Anxiety Scale (SAS) score of the intervention group was significantly lower than that of the control group (P < 0.05).The satisfaction of doctors and patients in the intervention groupwas significantly higher than that in the control group (P < 0.05). CONCLUSION: The application of the checklist-based nursing care process in patients with CTO intervention can significantly reduce the preoperative nursing care time, reduce patient anxiety, improve patients' and doctors' satisfaction with nursing care, and effectively reduce the occurrence of adverse events caused by nurses' omissions or inadequate instructions. TRIAL REGISTRATION: The protocol of the trial was registered retrospectively of Chinese Clinical Trial Registry (registration number ChiCTR2200056804, reg date17/02/2022).


Assuntos
Oclusão Coronária , Cuidados de Enfermagem , Intervenção Coronária Percutânea , Humanos , Oclusão Coronária/diagnóstico por imagem , Oclusão Coronária/cirurgia , Resultado do Tratamento , Intervenção Coronária Percutânea/efeitos adversos , Estudos Retrospectivos , Lista de Checagem , Doença Crônica , Sistema de Registros , Angiografia Coronária , Fatores de Risco
12.
Nutr Metab Cardiovasc Dis ; 33(7): 1437-1443, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37156667

RESUMO

BACKGROUND AND AIM: The Systemic Immune-Inflammation Index (SII) is a novel index of inflammation assessment that appears to be superior to the common single blood index in the assessment of cardiovascular disease. The purpose of this study was to investigate the association between SII and abdominal aortic calcification (AAC) in adults. METHODS AND RESULTS: Multivariate logistic regression, sensitivity analysis, and smoothing curve fitting were used to investigate the relationship between SII and AAC based on data from the National Health and Nutrition Examination Survey (NHANES) 2013-2014. Subgroup analysis and interaction tests were used to investigate whether this association was stable across populations. There was a positive association between SII and ACC in 3036 participants >40 years of age. In the fully adjusted model, each 100-unit increase in SII was associated with a 4% increase in the risk of developing severe AAC [1.04 (1.02, 1.07)]. Participants in the highest quartile of SII had a 47% higher risk of developing severe AAC than those in the lowest quartile [1.47 (1.10, 1.99)]. This positive association was more pronounced in older adults >60 years of age. CONCLUSIONS: SII is positively associated with AAC in US adults. Our findings imply that SII has the potential to improve AAC prevention in the general population.


Assuntos
Doenças da Aorta , Calcificação Vascular , Humanos , Idoso , Inquéritos Nutricionais , Fatores de Risco , Calcificação Vascular/diagnóstico por imagem , Calcificação Vascular/epidemiologia , Aorta Abdominal/diagnóstico por imagem , Inflamação/diagnóstico , Inflamação/epidemiologia
13.
Nucleic Acids Res ; 49(20): 11596-11613, 2021 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-34723322

RESUMO

Using the programmable RNA-sequence binding domain of the Pumilio protein, we FLAG-tagged Xist (inactivated X chromosome specific transcript) in live mouse cells. Affinity pulldown coupled to mass spectrometry was employed to identify a list of 138 candidate Xist-binding proteins, from which, Ssb (also known as the lupus autoantigen La) was validated as a protein functionally critical for X chromosome inactivation (XCI). Extensive XCI defects were detected in Ssb knockdown cells, including chromatin compaction, death of female mouse embryonic stem cells during in vitro differentiation and chromosome-wide monoallelic gene expression pattern. Live-cell imaging of Xist RNA reveals the defining XCI defect: Xist cloud formation. Ssb is a ubiquitous and versatile RNA-binding protein with RNA chaperone and RNA helicase activities. Functional dissection of Ssb shows that the RNA chaperone domain plays critical roles in XCI. In Ssb knockdown cells, Xist transcripts are unstable and misfolded. These results show that Ssb is critically involved in XCI, possibly as a protein regulating the in-cell structure of Xist.


Assuntos
Dobramento de RNA , RNA Longo não Codificante/química , Proteínas de Ligação a RNA/metabolismo , Inativação do Cromossomo X , Animais , Autoantígenos/química , Autoantígenos/metabolismo , Sítios de Ligação , Linhagem Celular , Camundongos , Ligação Proteica , RNA Longo não Codificante/metabolismo , Proteínas de Ligação a RNA/química , Proteínas de Ligação a RNA/genética
14.
Medicina (Kaunas) ; 59(2)2023 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-36837413

RESUMO

Background and Objectives: To investigate the digital measurement method for the plate trajectory of dynamic anterior plate-screw system for quadrilateral plate (DAPSQ), and then design a third-generation DAPSQ plate that conforms to the needs of the Chinese population through collating a large sample anatomical data. Materials and Methods: Firstly, the length of the pubic region, quadrilateral region, iliac region, and the total length of the DAPSQ trajectory were measured by a digital measurement approach in 22 complete pelvic specimens. Then, the results were compared with the direct measurement of pelvic specimens to verify the reliability of the digital measurement method. Secondly, 504 cases (834 hemilateral pelvis) of adult pelvic CT images were collected from four medical centers in China. The four DAPSQ trajectory parameters were obtained with the digital measurement method. Finally, the third-generation DAPSQ plate was designed, and its applicability was verified. Results: There was no statistically significant difference in the four trajectory parameters when comparing the direct measurement method with the digital measurement method (p > 0.05). The average lengths of the pubic region, quadrilateral region, iliac region, and the total length in Chinese population were (60.96 ± 5.39) mm, (69.11 ± 5.28) mm, (84.40 ± 6.41) mm, and (214.46 ± 10.15) mm, respectively. Based on the measurement results, six models of the DAPSQ plate including small size (A1,A2), medium size (B1,B2), and the large size (C1,C2) were designed. The verification experiment showed that all these six type plates could meet the requirement of 94.36% cases. Conclusions: A reliable computerized method for measuring irregular pelvic structure was proposed, which not only provided an anatomical basis for the design of the third-generation DAPSQ plate, but also provided a reference for the design of other pelvic fixation devices.


Assuntos
Fixação Interna de Fraturas , Fraturas Ósseas , Adulto , Humanos , Reprodutibilidade dos Testes , Acetábulo/cirurgia , Fraturas Ósseas/cirurgia , Pelve , Placas Ósseas , Parafusos Ósseos
15.
Glycobiology ; 32(3): 230-238, 2022 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-34939081

RESUMO

Maturity-onset diabetes of the young due to hepatocyte nuclear factor-1 alpha variants (HNF1A-MODY) causes monogenic diabetes. Individuals carrying damaging variants in HNF1A show decreased levels of α1-3,4 fucosylation, as demonstrated on antennary fucosylation of blood plasma N-glycans. The excellent diagnostic performance of this glycan biomarker in blood plasma N-glycans of individuals with HNF1A-MODY has been demonstrated using liquid chromatography methods. Here, we have developed a high-throughput exoglycosidase plate-based assay to measure α1-3,4 fucosylation levels in blood plasma samples. The assay has been optimized and its validity tested using 1000 clinical samples from a cohort of individuals with young-adult onset diabetes including cases with HNF1A-MODY. The α1-3,4 fucosylation levels in blood plasma showed a good differentiating power in identifying cases with damaging HNF1A variants, as demonstrated by receiver operating characteristic curve analysis with the AUC values of 0.87 and 0.95. This study supports future development of a simple diagnostic test to measure this glycan biomarker for application in a clinical setting.


Assuntos
Diabetes Mellitus Tipo 2 , Glicosídeo Hidrolases , Adulto , Biomarcadores , Proteína C-Reativa , Diabetes Mellitus Tipo 2/diagnóstico , Fator 1-alfa Nuclear de Hepatócito/genética , Humanos , Mutação
16.
J Transl Med ; 20(1): 409, 2022 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-36068536

RESUMO

BACKGROUND: With the development of digital pathology and the renewal of deep learning algorithm, artificial intelligence (AI) is widely applied in tumor pathology. Previous researches have demonstrated that AI-based tumor pathology may help to solve the challenges faced by traditional pathology. This technology has attracted the attention of scholars in many fields and a large amount of articles have been published. This study mainly summarizes the knowledge structure of AI-based tumor pathology through bibliometric analysis, and discusses the potential research trends and foci. METHODS: Publications related to AI-based tumor pathology from 1999 to 2021 were selected from Web of Science Core Collection. VOSviewer and Citespace were mainly used to perform and visualize co-authorship, co-citation, and co-occurrence analysis of countries, institutions, authors, references and keywords in this field. RESULTS: A total of 2753 papers were included. The papers on AI-based tumor pathology research had been continuously increased since 1999. The United States made the largest contribution in this field, in terms of publications (1138, 41.34%), H-index (85) and total citations (35,539 times). We identified the most productive institution and author were Harvard Medical School and Madabhushi Anant, while Jemal Ahmedin was the most co-cited author. Scientific Reports was the most prominent journal and after analysis, Lecture Notes in Computer Science was the journal with highest total link strength. According to the result of references and keywords analysis, "breast cancer histopathology" "convolutional neural network" and "histopathological image" were identified as the major future research foci. CONCLUSIONS: AI-based tumor pathology is in the stage of vigorous development and has a bright prospect. International transboundary cooperation among countries and institutions should be strengthened in the future. It is foreseeable that more research foci will be lied in the interpretability of deep learning-based model and the development of multi-modal fusion model.


Assuntos
Inteligência Artificial , Neoplasias da Mama , Bibliometria , Cognição , Feminino , Humanos , Publicações , Estados Unidos
17.
World J Urol ; 40(9): 2339-2345, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35821264

RESUMO

PURPOSE: To investigate the safety and efficacy of ultrasound-guided renal access and tract dilation using balloon dilators, as well as to identify suitable patients for this technique. METHODS: Consecutive patients undergoing ultrasound-guided PCNL using balloon dilators between December 2019 and June 2020 in seven large medical centers from China were prospectively enrolled. Demographic and perioperative parameters of the patients were collected. Logistic regression analysis was used to analyze factors that would affect the success rate of tract establishment using ultrasound-guided renal access and balloon dilation. RESULTS: A total of 170 patients were included in this study, among whom, 91.18% of the (155/170) patients had a successful tract establishment under ultrasound guidance on the first attempt. The stone-free rate was 83.5% and postoperative complications occurred in 14 patients (8.23%). In univariate analysis, history of ipsilateral surgery (p = 0.026), and stone diameter (p = 0.01) were significantly associated with tract establishment failure, while a larger width of the target calyx (p = 0.016) and the presence of hydronephrosis (p = 0.001) were significantly associated with a successful tract establishment. In multivariate analysis, only hydronephrosis in target calyx (p = 0.027) was a favorable factor for successful tract establishment, and the history of ipsilateral renal surgery (p = 0.012) was the only independent risk factor for failure of tract establishment. CONCLUSION: It was safe and effective to establish percutaneous renal access with balloon dilation under whole-process ultrasound monitoring during PCNL. Furthermore, patients with a hydronephrotic target calyx and without history of ipsilateral renal surgery were most suited to this technique. Trial registration CHiCTR1800014448.


Assuntos
Hidronefrose , Cálculos Renais , Nefrostomia Percutânea , Dilatação/métodos , Humanos , Hidronefrose/diagnóstico por imagem , Hidronefrose/cirurgia , Cálculos Renais/diagnóstico por imagem , Cálculos Renais/cirurgia , Nefrostomia Percutânea/métodos , Decúbito Ventral , Ultrassonografia de Intervenção
18.
Nanotechnology ; 33(16)2022 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-35008068

RESUMO

In order to meet the requirements of ultra-fast real-time monitoring of sarin simulator with high sensitivity and selectivity, it is of great significance to develop high performance dimethyl methylphonate (DMMP) sensor. Herein, we proposed a DMMP sensor based on p-hexafluoroisopropanol phenyl (HFIPPH) modified self-assembled single-walled carbon nanotubes (SWCNTs) with field effect transistor (FET) structure. The self-assembly method provides a 4 nanometres thick and micron sized SWCNT channel, with high selectivity to DMMP. The proposed SWCNTs-HFIPPH based sensor exhibits remarkably higher response to DMMP than bare SWCNT based gas sensor within only few seconds. The gas sensing response of SWCNTs-HFIPPH based sensor for 1 ppm DMMP is 18.2%, and the response time is about 10 s. What's more, the gas sensor we proposed here shows excellent selectivity and reproducibility, and the limitation of detection is as low as ppb level. The proposed method lays the foundation for miniaturization and integration of DMMP sensors, expecting to develop detection system for practical sarin sensing application.

19.
Nanotechnology ; 34(10)2022 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-36562507

RESUMO

Ethanol is a harmful volatile organic compound (VOC) for human health. Currently, zinc oxide (ZnO) is one of the most popular metal oxide semiconductors for VOCs detection but suffering from a lack of selectivity, poor response, and slow response/recovery speeds. Herein, we successfully synthesized the ZnO/Ti3C2Txnanocomposites via a facile hydrothermal method, in which ZnO nanoparticles were uniformly grown on two-dimensional (2D) Ti3C2Txnanosheets. As a result, the ZnO/Ti3C2Txnanocomposites showed a significant improvement in the ethanol-sensing performance, when it compared to the pure ZnO and Ti3C2Txsamples. In particular, ZnO doped with 5 mg of Ti3C2Txshowed an ultra-high response (79) to 100 ppm ethanol, a short response/recovery time (22 s/34 s to 50 ppm ethanol), a low limit of detection (1 ppm) and a long-term stability. The excellent ethanol sensing properties are mainly attributed to the coupling effect between ZnO and Ti3C2Txof composites. The ZnO nanoparticles are uniformly distributed on the 2D Ti3C2Txplatform, which can provide more gas adsorption sites. Simultaneously, the presence of hybrid heterojunctions further enhances the response in the sensing process.

20.
Nanotechnology ; 33(37)2022 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-35605577

RESUMO

A delay line-type surface acoustic wave (SAW) gas sensor based on p-hexafluoroisopropanol phenyl (HFIPPH) functionalized multi-walled carbon nanotube (MWCNT) film is developed to detect organophosphorus dimethyl methylphosphonate (DMMP) vapor (a simulant of chemical nerve agent sarin). Inspired by the transfer process of Cu-based graphene, a uniform and size-controllable HFIPPH-MWCNT film is successfully prepared on the SAW device via a wet-etching transfer method. For the first time, we use the method of measuring the change of the sensor's insertion loss to achieve the detection of ultra-low concentration DMMP vapor. The designed sensor exhibits a fast response/recovery time about 3 s/50 s, and a low detection limit of 0.1 ppm. Additionally, the stability and selectivity of the sensor and the influence of humidity on its response are evaluated through experiments. The acoustoelectric effect is proved to be the sensing mechanism of the sensor insertion loss response.

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