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1.
Sensors (Basel) ; 24(8)2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38676169

RESUMO

Accurate and reliable pose estimation of boom-type roadheaders is the key to the forming quality of the tunneling face in coal mines, which is of great importance to improve tunneling efficiency and ensure the safety of coal mine production. The multi-laser-beam target-based visual localization method is an effective way to realize accurate and reliable pose estimation of a roadheader body. However, the complex background interference in coal mines brings great challenges to the stable and accurate segmentation and extraction of laser beam features, which has become the main problem faced by the long-distance visual positioning method of underground equipment. In this paper, a semantic segmentation network for underground laser beams in coal mines, RCEAU-Net, is proposed based on U-Net. The network introduces residual connections in the convolution of the encoder and decoder parts, which effectively fuses the underlying feature information and improves the gradient circulation performance of the network. At the same time, by introducing cascade multi-scale convolution in the skipping connection section, which compensates for the lack of contextual semantic information in U-Net and improves the segmentation effect of the network model on tiny laser beams at long distance. Finally, the introduction of an efficient multi-scale attention module with cross-spatial learning in the encoder enhances the feature extraction capability of the network. Furthermore, the laser beam target dataset (LBTD) is constructed based on laser beam target images collected from several coal mines, and the proposed RCEAU-Net model is then tested and verified. The experimental results show that, compared with the original U-Net, RCEAU-Net can ensure the real-time performance of laser beam segmentation while increasing the Accuracy by 0.19%, Precision by 2.53%, Recall by 22.01%, and Intersection and Union Ratio by 8.48%, which can meet the requirements of multi-laser-beam feature segmentation and extraction under complex backgrounds in coal mines, so as to further ensure the accuracy and stability of long-distance visual positioning for boom-type roadheaders and ensure the safe production in the working face.

2.
J Proteomics ; 300: 105179, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38657733

RESUMO

This study aims to investigate the potential regulatory network responsible for the meat quality using multi-omics to help developing better varieties. Slaughter performance and meat quality of Shuxing No.1 rabbit outperformed IRA rabbit according to the tested rabbit parameters. Differentially expressed genes (DEGs) and differentially abundance proteins (DAPs) were involved in meat quality-related pathways, such as PI3K - Akt and MAPK signaling pathways. Only SMTNL1 and PM20D2 shared between DEGs and DAPs. Olfactory-sensitive undecanal, a differentially abundant metabolite (DAM) in volatilomics (vDAMs), correlated with all of the remaining 11 vDAMs, and most of 12 vDAMs were associated with amino acid metabolism. Integration revealed that 829 DEGs/DAPs were associated with 15 DAMs in four KEGG pathways, such as melatonin (a DAM in widely targeted metabolomics) was significantly positively correlated with ALDH and negatively correlated with RAB3D and CAT in the tryptophan metabolism pathway. This study sheds light on the potential mechanisms that contribute to the improved meat quality and flavor. SIGNIFICANCE: Shuxing No.1 rabbit is a new breed of meat rabbit in the Chinese market. In meat marketing, meat quality usually determines the purchase intention of consumers. Determining the biological and molecular mechanisms of meat quality in meat rabbit is essential for developing strategies to improve meat quality. According to the tested rabbit parameters, this study ascertained that the slaughter performance and meat quality of Shuxing No.1 rabbit surpasses that of IRA rabbit. The present study profiled the transcriptome, proteome, widely targeted metabolome, and volatilome of longissimus dorsi from Shuxing No.1 rabbit and IRA rabbit. The study found that meat quality and flavor-related tryptophan metabolism pathway is enriched with many DEGs/DAPs (including ALDH, RAB3D, and CAT), as well as a DAM, melatonin. This study sheds light on the potential mechanisms that contribute to the improved meat quality and flavor.


Assuntos
Carne , Proteômica , Transcriptoma , Animais , Coelhos , Proteômica/métodos , Carne/análise , Metabolômica , Redes Reguladoras de Genes , Proteoma/metabolismo , Proteoma/análise , Músculo Esquelético/metabolismo
3.
Int J Biol Sci ; 20(6): 2111-2129, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38617529

RESUMO

Gaucher disease (GD), a rare hereditary lysosomal storage disorder, occurs due to a deficiency in the enzyme ß-glucocerebrosidase (GCase). This deficiency leads to the buildup of substrate glucosylceramide (GlcCer) in macrophages, eventually resulting in various complications. Among its three types, GD2 is particularly severe with neurological involvements. Current treatments, such as enzyme replacement therapy (ERT), are not effective for GD2 and GD3 due to their inability to cross the blood-brain barrier (BBB). Other treatment approaches, such as gene or chaperone therapies are still in experimental stages. Additionally, GD treatments are costly and can have certain side effects. The successful use of messenger RNA (mRNA)-based vaccines for COVID-19 in 2020 has sparked interest in nucleic acid-based therapies. Remarkably, mRNA technology also offers a novel approach for protein replacement purposes. Additionally, self-amplifying RNA (saRNA) technology shows promise, potentially producing more protein at lower doses. This review aims to explore the potential of a cost-effective mRNA/saRNA-based approach for GD therapy. The use of GCase-mRNA/saRNA as a protein replacement therapy could offer a new and promising direction for improving the quality of life and extending the lifespan of individuals with GD.


Assuntos
Doença de Gaucher , Glucosilceramidase , Humanos , Glucosilceramidase/genética , Doença de Gaucher/genética , Doença de Gaucher/terapia , RNA Mensageiro/genética , Vacinas contra COVID-19 , Qualidade de Vida
4.
J Chin Med Assoc ; 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38648194

RESUMO

BACKGROUND: Medical students need to build a solid foundation of knowledge to become physicians. Clerkship is often considered the first transition point, and clerkship performance is essential for their development. We hope to identify subjects that could predict the clerkship performance, thus helping medical students learn more efficiently to achieve high clerkship performance. METHODS: This cohort study collected background and academic data from medical students who graduated between 2011 and 2019. Prediction models were developed by machine learning techniques to identify the affecting features in predicting the pre-clerkship performance and clerkship performance. Following serial processes of data collection, data pre-processing before machine learning, and techniques and performance of machine learning, different machine learning models were trained and validated using the 10-fold cross-validation method. RESULTS: Thirteen subjects from the pre-med stage and ten subjects from the basic medical science stage with an area under the ROC curve (AUC) greater than 0.7 for either pre-clerkship performance or clerkship performance were found. In each subject category, medical humanities and sociology in social science, chemistry and physician scientist-related training in basic science, and pharmacology, immunology-microbiology, and histology in basic medical science have predictive abilities for clerkship performance above the top tertile. Using a machine learning technique based on random forest, the prediction model predicted clerkship performance with 95% accuracy and 88% AUC. CONCLUSION: Clerkship performance was predicted by selected subjects or combination of different subject categories in the pre-med and basic medical science stages. The demonstrated predictive ability of subjects or categories in the medical program may facilitate students' understanding of how these subjects or categories of the medical program relate to their performance in the clerkship to enhance their preparedness for the clerkship.

5.
Mikrochim Acta ; 191(5): 254, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38594554

RESUMO

A fluorescent multichannel sensor array has been established based on three carbon dots derived from Tibetan medicine waste for rapid quantification and discrimination of six heavy metal ions. Due to the chelation between metal ions and carbon dots (CDs), this fluorescence "turn off" mode sensing array can quantify six metal ions as low as "µM" level. Moreover, the six heavy metal ions display varying quenching effects on these three CDs owing to diverse chelating abilities between each other, producing differential fluorescent signals for three sensing channels, which can be plotted as specific fingerprints and converted into intuitive identification profiles via principal component analysis (PCA) and hierarchical cluster analysis (HCA) technologies to accurately distinguish Cu2+, Fe3+, Mn2+, Ag+, Ce4+, and Ni2+ with the minimum differentiated concentration of 5 µM. Valuably, this sensing array unveils good sensitivity, exceptional selectivity, ideal stability, and excellent anti-interference ability for both mixed standards and actual samples. Our contribution provides a novel approach for simultaneous determination of multiple heavy metal ions in environmental samples, and it will inspire the development of other advanced optical sensing array for simultaneous quantification and discrimination of multiple targets.

6.
Abdom Radiol (NY) ; 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38683216

RESUMO

OBJECTIVE: To study the impact of Gx on quantification of hepatic fat contents under metabolic dysfunction-associated steatotic liver disease (MASLD) imaged on VIBE Dixon in hepatobiliary specific phase. METHODS: Forty-two rabbits were randomly divided into control group (n = 10) and high-fat diet group (n = 32). Imaging was performed before enhancement (Pre-Gx) and at the 13th (Post-Gx13) and 17th (Post-Gx17) min after Gx enhancement with 2E- and 6E-VIBE Dixon to determine hepatic proton density fat fractions (PDFF). PDFFs were compared with vacuole percentage (VP) measured under histopathology. RESULTS: 33 animals were evaluated and including control group (n = 11) and MASLD group (n = 22). Pre-Gx, Post-Gx13, Post-Gx17 PDFFs under 6E-VIBE Dixon had strong correlations with VPs (r2 = 0.8208-0.8536). PDFFs under 2E-VIBE Dixon were reduced significantly (P < 0.001) after enhancement (r2 = 0.7991/0.8014) compared with that before enhancement (r2 = 0.7643). There was no significant difference between PDFFs of Post-Gx13 and Post-Gx17 (P = 0.123) for which the highest consistency being found with 6E-VIBE Dixon before enhancement (r2 = 0.8536). The signal intensity of the precontrast compared with the postcontrast, water image under 2E-VIBE Dixon increased significantly (P < 0.001), fat image showed no significant difference (P = 0.754). CONCLUSION: 2E- and 6E-VIBE Dixon can obtain accurate PDFFs in the hepatobiliary specific phase from 13 to 17th min after Gx enhancement. On 2E-VIBE Dixon (FA = 10°), effective minimization of T1 Bias by the Gx administration markedly improved the accuracy of the hepatic PDFF quantification.

8.
Biol Psychiatry ; 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38521158

RESUMO

BACKGROUND: Electroconvulsive therapy (ECT) is an effective treatment for patients with major depressive disorder (MDD), but its underlying neural mechanisms remain largely unknown. The aim of this study was to identify changes in brain connectome dynamics after ECT in MDD and to explore their associations with treatment outcome. METHODS: We collected longitudinal resting-state functional magnetic resonance imaging data from 80 patients with MDD (50 with suicidal ideation [MDD-SI] and 30 without [MDD-NSI]) before and after ECT and 37 age- and sex-matched healthy control participants. A multilayer network model was used to assess modular switching over time in functional connectomes. Support vector regression was used to assess whether pre-ECT network dynamics could predict treatment response in terms of symptom severity. RESULTS: At baseline, patients with MDD had lower global modularity and higher modular variability in functional connectomes than control participants. Network modularity increased and network variability decreased after ECT in patients with MDD, predominantly in the default mode and somatomotor networks. Moreover, ECT was associated with decreased modular variability in the left dorsal anterior cingulate cortex of MDD-SI but not MDD-NSI patients, and pre-ECT modular variability significantly predicted symptom improvement in the MDD-SI group but not in the MDD-NSI group. CONCLUSIONS: We highlight ECT-induced changes in MDD brain network dynamics and their predictive value for treatment outcome, particularly in patients with SI. This study advances our understanding of the neural mechanisms of ECT from a dynamic brain network perspective and suggests potential prognostic biomarkers for predicting ECT efficacy in patients with MDD.

9.
BMC Anesthesiol ; 24(1): 121, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38539078

RESUMO

INTRODUCTION: Postoperative nausea and vomiting (PONV) is one of the most common adverse events following orthognathic surgery. It's a distressing feeling for patients and continues to be the cause of postoperative complications such as bleeding, delayed healing, and wound infection. This scoping review aims to identify effective PONV prophylaxis strategies during orthognathic surgery that have emerged in the past 15 years. METHODS: We searched Pubmed, Cochrane Controlled Register of Trials, and Embase from 2008 to May 2023. Studies meeting the following criteria were eligible for inclusion: (1) recruited patients undergo any orthognathic surgery; (2) evaluated any pharmacologic or non-pharmacologic method to prevent PONV. Studies meeting the following criteria were excluded: (1) case series, review papers, or retrospective studies; (2) did not report our prespecified outcomes. RESULTS: Twenty-one studies were included in this review. Pharmacological methods for PONV prevention include ondansetron and dexamethasone (3 studies), peripheral nerve block technique (4 studies), dexmedetomidine (1 study), pregabalin (2 studies), nefopam (2 studies), remifentanil (1 study), propofol (2 studies), and penehyclidine (1 study). Non-pharmacologic methods include capsicum plaster (1 study), throat packs (2 studies) and gastric aspiration (2 studies). CONCLUSIONS: Based on current evidence, we conclude that prophylactic antiemetics like dexamethasone, ondansetron, and penehyclidine are the first defense against PONV. Multimodal analgesia with nerve block techniques and non-opioid analgesics should be considered due to their notable opioid-sparing and PONV preventive effect. For the non-pharmacological methods, throat packs are not recommended for routine use because of their poor effect and serious complications. More prospective RCTs are required to confirm whether gastric aspiration can prevent PONV effectively for patients undergoing orthognathic surgery.


Assuntos
Antieméticos , Cirurgia Ortognática , Humanos , Náusea e Vômito Pós-Operatórios/prevenção & controle , Náusea e Vômito Pós-Operatórios/tratamento farmacológico , Ondansetron/uso terapêutico , Estudos Prospectivos , Estudos Retrospectivos , Antieméticos/uso terapêutico , Dexametasona/uso terapêutico
10.
Cell Commun Signal ; 22(1): 164, 2024 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-38448900

RESUMO

Pancreatic neuroendocrine tumors (PanNETs), though uncommon, have a high likelihood of spreading to other body parts. Previously, the genetic diversity and evolutionary patterns in metastatic PanNETs were not well understood. To investigate this, we performed multiregion sampling whole-exome sequencing (MRS-WES) on samples from 10 patients who had not received prior treatment for metastatic PanNETs. This included 29 primary tumor samples, 31 lymph node metastases, and 15 liver metastases. We used the MSK-MET dataset for survival analysis and validation of our findings. Our research indicates that mutations in the MEN1/DAXX genes might trigger the early stages of PanNET development. We categorized the patients based on the presence (MEN1/DAXXmut, n = 7) or absence (MEN1/DAXXwild, n = 3) of these mutations. Notable differences were observed between the two groups in terms of genetic alterations and clinically relevant mutations, confirmed using the MSK-MET dataset. Notably, patients with mutations in MEN1/DAXX/ATRX genes had a significantly longer median overall survival compared to those without these mutations (median not reached vs. 43.63 months, p = 0.047). Multiplex immunohistochemistry (mIHC) analysis showed a more prominent immunosuppressive environment in metastatic tumors, especially in patients with MEN1/DAXX mutations. These findings imply that MEN1/DAXX mutations lead PanNETs through a unique evolutionary path. The disease's progression pattern indicates that PanNETs can spread early, even before clinical detection, highlighting the importance of identifying biomarkers related to metastasis to guide personalized treatment strategies.


Assuntos
Neoplasias Hepáticas , Tumores Neuroendócrinos , Neoplasias Pancreáticas , Humanos , Sequenciamento do Exoma , Tumores Neuroendócrinos/genética , Genômica , Neoplasias Hepáticas/genética , Neoplasias Pancreáticas/genética , Microambiente Tumoral
12.
Discov Oncol ; 15(1): 63, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38443703

RESUMO

BACKGROUND AND OBJECTIVES: Colorectal mucinous adenocarcinoma (MAC) is a particular pathological type that has yet to be thoroughly studied. This study aims to investigate the characteristics of colorectal MAC-related genes in colorectal cancer (CRC), explore the role of MAC-related genes in accurately classifying CRC, and further construct a prognostic signature. METHODS: CRC samples were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). MAC-related differentially expressed genes (DEGs) were analyzed in TCGA samples. Based on colorectal MAC-related genes, TCGA CRC samples were molecularly typed by the non-negative matrix factorization (NMF). According to the molecular subtype characteristics, the RiskScore signature was constructed through univariate Cox, the least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses. Clinical significance in CRC of the RiskScore signature was analyzed. A nomogram was further built based on the RiskScore signature. RESULTS: From the colorectal MAC-related genes, three distinct molecular subtypes were identified. A RiskScore signature composed of six CRC subtype-related genes (CALB1, MMP1, HOXC6, ZIC2, SFTA2, and HYAL1) was constructed. Patients with high-RiskScores had the worse prognoses. RiskScores led to differences in gene mutation characteristics, antitumor drug sensitivity, and tumor microenvironment of CRC. A nomogram based on the signature was developed to predict the one-, three-, and five-year survival of CRC patients. CONCLUSION: MAC-related genes were able to classify CRC. A RiskScore signature based on the colorectal MAC-related molecular subtype was constructed, which had important clinical significance for guiding the accurate stratification of CRC patients.

13.
Microorganisms ; 12(3)2024 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-38543565

RESUMO

Monochamus alternatus is a serious trunk-boring pest. The isolation and utilization of entomopathogenic fungi to manage M. alternatus is important. Here, a new strain GQH6 of Metarhizium robertsii, isolated from the Loess Plateau, was identified morphologically and molecularly. The virulence of the strain GQH6 against the third-instar larvae of M. alternatus was studied. Then, the pathological process, including symptom observation and histopathological observation, was also researched. The corrected mortality was 100% at 109 and 108 conidia/mL, and 88.89 ± 5.88% at 107 conidia/mL. The LC50 was 1.93 × 106 conidia/mL and the LC90 was 1.35 × 107 conidia/mL. And the LT50 of the strain GQH6 was 3.96 days at 109 conidia/mL, and 4.99 days at 108 conidia/mL. These virulence indices showed high virulence against M. alternatus larvae. In addition, the symptoms of the infected M. alternatus larvae were obvious. After one day, dark spots appeared and increased in number. By four days, white mycelia appeared. Finally, the larvae body became green. Similarly, the histopathological changes after infection were obvious, mainly manifested in muscle tissue rupture, adipose tissue fracture and midgut disintegration. These results demonstrated that the M. robertsii strain GQH6 isolated from the Loess Plateau was highly virulent against M. alternatus larvae of the third instar.

14.
Psychiatry Res Neuroimaging ; 339: 111788, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38335560

RESUMO

OBJECTIVE: Our objective is to innovatively integrate both linear and nonlinear characteristics of brain signals in Electroconvulsive Therapy (ECT) research, with the goal of uncovering deeper insights into the pathogenesis of Major Depressive Disorder (MDD) and identifying novel targets for other physical intervention therapies. METHODS: We measured brain entropy (BEN) in 42 MDD patients and 42 matched healthy controls (HC) using rs-fMRI data. Brain regions that differed significantly in patients with MDD before and after ECT were extracted. Then, we use these brain regions as seed points to investigate the differences in whole-brain resting-state functional connectivity (RSFC) patterns before and after ECT. RESULTS: Compared to HCs, patients had higher BEN levels in the right precuneus (PCUN.R) and right angular gyrus (ANG.R). After ECT, patients had lower BEN levels in the PCUN.R and ANG.R. Compared with before ECT, patients showed significantly increased RSFC after ECT between the PCUN.R and right middle temporal gyrus and ANG.R. Significantly increased RSFC was observed between the ANG.R and right middle frontal gyrus and right supramarginal gyrus after ECT. CONCLUSION: Combining the linear and nonlinear characteristics of brain signals can effectively explore the pathogenesis of depression and provide new targets for ECT.


Assuntos
Transtorno Depressivo Maior , Eletroconvulsoterapia , Humanos , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/terapia , Depressão , Entropia , Imageamento por Ressonância Magnética , Encéfalo/diagnóstico por imagem
15.
J Med Chem ; 67(5): 3419-3436, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38385428

RESUMO

Androgen receptor (AR) antagonists play important roles in the treatment of castration-resistant prostate cancer (CRPC). The glucocorticoid receptor (GR) upregulation leads to drug resistance for clinically used antiandrogens. Therefore, blocking AR/GR signaling simultaneously has become an efficient strategy to overcome the drug resistance of CRPC. Our previous work indicated that Z19 could inhibit the activity of both AR and GR. Herein, we optimized the structure of Z19 and identified GA32 as a potent AR/GR dual inhibitor. GA32 efficiently reduced the mRNA and protein levels of AR/GR downstream genes. GA32 efficiently inhibited the proliferation of enzalutamide resistance CRPC both in vitro and in vivo. GA32 could directly bind to AR and GR, and the predicted binding modes for GA32 with AR/GR suggested that GA32 binds to the AR or GR hormone binding pocket. This work provides a potential lead compound with dual AR/GR inhibitory activity to conquer the drug resistance of CRPC.


Assuntos
Neoplasias de Próstata Resistentes à Castração , Receptores Androgênicos , Masculino , Humanos , Receptores Androgênicos/metabolismo , Antagonistas de Androgênios/farmacologia , Antagonistas de Androgênios/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/metabolismo , Receptores de Glucocorticoides/metabolismo , Resistencia a Medicamentos Antineoplásicos , Antagonistas de Receptores de Andrógenos/farmacologia , Antagonistas de Receptores de Andrógenos/uso terapêutico , Nitrilas/uso terapêutico , Linhagem Celular Tumoral
16.
Hum Mol Genet ; 33(10): 884-893, 2024 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-38340456

RESUMO

Patent ductus arteriosus (PDA) is a common form of congenital heart disease. The MYH6 gene has important effects on cardiovascular growth and development, but the effect of variants in the MYH6 gene promoter on ductus arteriosus is unknown. DNA was extracted from blood samples of 721 subjects (428 patients with isolated and sporadic PDA and 293 healthy controls) and analyzed by sequencing for MYH6 gene promoter region variants. Cellular function experiments with three cell lines (HEK-293, HL-1, and H9C2 cells) and bioinformatics analyses were performed to verify their effects on gene expression. In the MYH6 gene promoter, 11 variants were identified. Four variants were found only in patients with PDA and 2 of them (g.3434G>C and g.4524C>T) were novel. Electrophoretic mobility shift assay showed that the transcription factors bound by the promoter variants were significantly altered in comparison to the wild-type in all three cell lines. Dual luciferase reporter showed that all the 4 variants reduced the transcriptional activity of the MYH6 gene promoter (P < 0.05). Prediction of transcription factors bound by the variants indicated that these variants alter the transcription factor binding sites. These pathological alterations most likely affect the contraction of the smooth muscle of ductus arteriosus, leading to PDA. This study is the first to focus on variants at the promoter region of the MYH6 gene in PDA patients with cellular function tests. Therefore, this study provides new insights to understand the genetic basis and facilitates further studies on the mechanism of PDA formation.


Assuntos
Miosinas Cardíacas , Permeabilidade do Canal Arterial , Cadeias Pesadas de Miosina , Regiões Promotoras Genéticas , Humanos , Cadeias Pesadas de Miosina/genética , Permeabilidade do Canal Arterial/genética , Permeabilidade do Canal Arterial/patologia , Masculino , Feminino , Estudos de Casos e Controles , Células HEK293 , Criança , Pré-Escolar , Lactente , Adulto , Linhagem Celular , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
17.
Blood Adv ; 8(7): 1667-1682, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38286463

RESUMO

ABSTRACT: Congenital neutropenia (CN) is a genetic disorder characterized by persistent or intermittent low peripheral neutrophil counts, thus increasing susceptibility to bacterial and fungal infections. Various forms of CN, caused by distinct genetic mutations, exhibit differential responses to granulocyte colony-stimulating factor (G-CSF) therapy, with the underlying mechanisms not fully understood. This study presents an in-depth comparative analysis of clinical and immunological features in 5 CN patient groups (severe congenital neutropenia [SCN]1, SCN3, cyclic neutropenia [CyN], warts, hypogammaglobulinaemia, infections and myelokathexis [WHIM], and Shwachman-Bodian-Diamond Syndrome [SBDS]) associated with mutations in ELANE, HAX1, CXCR4, and SBDS genes. Our analysis led to the identification of 11 novel mutations in ELANE and 1 each in HAX1, CXCR4, and G6PC3 genes. Investigating bone marrow (BM) granulopoiesis and blood absolute neutrophil count after G-CSF treatment, we found that SCN1 and SCN3 presented with severe early-stage disruption between the promyelocyte and myelocyte, leading to a poor response to G-CSF. In contrast, CyN, affected at the late polymorphonuclear stage of neutrophil development, showed a strong G-CSF response. WHIM, displaying normal neutrophil development, responded robustly to G-CSF, whereas SBDS, with moderate disruption from the early myeloblast stage, exhibited a moderate response. Notably, SCN1 uniquely impeded neutrophil development, whereas SCN3, CyN, WHIM, and SBDS also affected eosinophils and basophils. In addition, SCN1, SCN3, and CyN presented with elevated serum immunoglobulins, increased BM plasma cells, and higher A Proliferation-Inducing Ligand levels. Our study reveals a strong correlation between the stage and severity of granulocyte development disruption and the efficacy of G-CSF therapy.


Assuntos
Síndrome Congênita de Insuficiência da Medula Óssea , Eosinófilos , Fator Estimulador de Colônias de Granulócitos , Neutropenia/congênito , Humanos , Fator Estimulador de Colônias de Granulócitos/farmacologia , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Mutação , Proteínas Adaptadoras de Transdução de Sinal
18.
J Magn Reson Imaging ; 2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38236785

RESUMO

BACKGROUND: Quantitative in-situ pH mapping of gliomas is important for therapeutic interventions, given its significant association with tumor progression, invasion, and metastasis. Although chemical exchange saturation transfer (CEST) offers a noninvasive way for pH imaging based on the pH-dependent exchange rate (ksw ), the reliable quantification of ksw in glioma remains constrained due to technical challenges. PURPOSE: To quantify the pH of gliomas by measuring the proton exchange rate through optimized omega plot analysis. STUDY TYPE: Prospective. PHANTOMS/ANIMAL MODEL/SUBJECTS: Creatine and murine brain lysates phantoms, six rats with glioma xenograft model, and three patients with World Health Organization grade 2-4 gliomas. FIELD STRENGTH/SEQUENCE: 11.7 T, 7.0 T, CEST imaging, T2 -weighted (T2 W) imaging, and T1 -mapping. ASSESSMENT: Omega plot analysis, quasi-steady-state (QUASS) analysis, multi-pool Lorentzian fitting, amine and amide concentration-independent detection, pH enhanced method with the combination of amide and guanidyl (pHenh ), and magnetization transfer ratio (MTR) were utilized for pH metric quantification. The clinical outcomes were determined through radiologic follow-up and histopathological analysis. STATISTICAL TESTS: Mann-Whitney U test was performed to compare glioma with normal tissue, and Pearson's correlation analysis was used to assess the relationship between ksw and other parameters. RESULTS: In vitro experiments reveal that the determined ksw at 2 ppm increases exponentially with pH (creatine phantoms: ksw = 106 + 0.147 × 10(pH-4.198) ; lysates: ksw = 185.1 + 0.101 × 10(pH-3.914) ). Omega plot analysis exhibits a linear correlation between 1/MTRRex and 1/ω1 2 in the glioma xenografts (R2 > 0.98) and glioma patients (R2 > 0.99). The exchange rate in the rat glioma decreases compared to the contralateral normal tissue (349.46 ± 30.40 s-1 vs. 403.54 ± 51.01 s-1 , P = 0.025), while keeping independence from changes in concentration (r = 0.5037, P = 0.095). Similar pattern was observed in human data. DATA CONCLUSION: Utilizing QUASS-based, spillover-, and MT-corrected omega plot analysis for the measurement of exchange rates, offers a feasible method for quantifying pH within glioma. LEVEL OF EVIDENCE: NA TECHNICAL EFFICACY: Stage 1.

19.
Int J Biol Macromol ; 254(Pt 1): 127751, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38287593

RESUMO

In order to meet the market demand and avoid the increase of operation amount and cleaning cost in the process of ultrafiltration, it is particularly important to find more practical and efficient methods to control and improve membrane fouling. In this study, the ions in the ultrafiltration process were regulated to affect membrane surface proteins composition (lactoferrin, α-lactalbumin, ß-lactoglobulin A and ß-lactoglobulin B) and delay membrane fouling. It was found that Na+ (21 mmol/L), Zn2+ (0.25 mmol/L) and K+ (44 mmol/L) was added at 4 min, 8 min and 12 min, respectively during ultrafiltration process. The continuous regulation slowed down the decline rate of membrane flux and reduced the content of α-lactalbumin, ß-lactoglobulin A and ß-lactoglobulin B on the membrane surface analyzed by HPLC. This could reduce the irreversible membrane fouling of proteins cake resistance. Furthermore, the ions concentration was also investigated after filtration. The concentration of K+ was increased significantly and other ions concentration was not significantly changed after continuous regulation such Na+, Mg2+, Zn2+ and Ca2+ compared to control. Therefore, dynamic ionic regulation of whey protein ultrafiltration process is a simple and effective method, which provides technical theoretical basis for optimizing and improving membrane technology.


Assuntos
Ultrafiltração , Purificação da Água , Ultrafiltração/métodos , Proteínas do Soro do Leite , Lactalbumina , Cromatografia Líquida de Alta Pressão , Lactoglobulinas , Proteínas de Membrana , Fatores de Transcrição , Íons , Membranas Artificiais , Purificação da Água/métodos
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