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1.
Nat Chem Biol ; 19(7): 815-824, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36823351

RESUMO

Creatine kinases (CKs) provide local ATP production in periods of elevated energetic demand, such as during rapid anabolism and growth. Thus, creatine energetics has emerged as a major metabolic liability in many rapidly proliferating cancers. Whether CKs can be targeted therapeutically is unknown because no potent or selective CK inhibitors have been developed. Here we leverage an active site cysteine present in all CK isoforms to develop a selective covalent inhibitor of creatine phosphagen energetics, CKi. Using deep chemoproteomics, we discover that CKi selectively engages the active site cysteine of CKs in cells. A co-crystal structure of CKi with creatine kinase B indicates active site inhibition that prevents bidirectional phosphotransfer. In cells, CKi and its analogs rapidly and selectively deplete creatine phosphate, and drive toxicity selectively in CK-dependent acute myeloid leukemia. Finally, we use CKi to uncover an essential role for CKs in the regulation of proinflammatory cytokine production in macrophages.


Assuntos
Creatina Quinase , Creatina , Creatina Quinase/química , Creatina Quinase/metabolismo , Creatina/farmacologia , Cisteína , Fosfotransferases , Isoformas de Proteínas
2.
Blood ; 140(17): 1875-1890, 2022 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-35839448

RESUMO

The fusion gene MLL/AF4 defines a high-risk subtype of pro-B acute lymphoblastic leukemia. Relapse can be associated with a lineage switch from acute lymphoblastic to acute myeloid leukemia, resulting in poor clinical outcomes caused by resistance to chemotherapies and immunotherapies. In this study, the myeloid relapses shared oncogene fusion breakpoints with their matched lymphoid presentations and originated from various differentiation stages from immature progenitors through to committed B-cell precursors. Lineage switching is linked to substantial changes in chromatin accessibility and rewiring of transcriptional programs, including alternative splicing. These findings indicate that the execution and maintenance of lymphoid lineage differentiation is impaired. The relapsed myeloid phenotype is recurrently associated with the altered expression, splicing, or mutation of chromatin modifiers, including CHD4 coding for the ATPase/helicase of the nucleosome remodelling and deacetylation complex. Perturbation of CHD4 alone or in combination with other mutated epigenetic modifiers induces myeloid gene expression in MLL/AF4+ cell models, indicating that lineage switching in MLL/AF4 leukemia is driven and maintained by disrupted epigenetic regulation.


Assuntos
Proteína de Leucina Linfoide-Mieloide , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Proteína de Leucina Linfoide-Mieloide/genética , Proteína de Leucina Linfoide-Mieloide/metabolismo , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/metabolismo , Epigênese Genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Genes Reguladores , Cromatina
3.
Plant Cell ; 33(5): 1492-1505, 2021 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-33580260

RESUMO

Compared with root development regulated by external nutrients, less is known about how internal nutrients are monitored to control plasticity of shoot development. In this study, we characterize an Arabidopsis thaliana transceptor, NRT1.13 (NPF4.4), of the NRT1/PTR/NPF family. Different from most NRT1 transporters, NRT1.13 does not have the conserved proline residue between transmembrane domains 10 and 11; an essential residue for nitrate transport activity in CHL1/NRT1.1/NPF6.3. As expected, when expressed in oocytes, NRT1.13 showed no nitrate transport activity. However, when Ser 487 at the corresponding position was converted back to proline, NRT1.13 S487P regained nitrate uptake activity, suggesting that wild-type NRT1.13 cannot transport nitrate but can bind it. Subcellular localization and ß-glucuronidase reporter analyses indicated that NRT1.13 is a plasma membrane protein expressed at the parenchyma cells next to xylem in the petioles and the stem nodes. When plants were grown with a normal concentration of nitrate, nrt1.13 showed no severe growth phenotype. However, when grown under low-nitrate conditions, nrt1.13 showed delayed flowering, increased node number, retarded branch outgrowth, and reduced lateral nitrate allocation to nodes. Our results suggest that NRT1.13 is required for low-nitrate acclimation and that internal nitrate is monitored near the xylem by NRT1.13 to regulate shoot architecture and flowering time.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Flores/fisiologia , Nitratos/farmacologia , Brotos de Planta/anatomia & histologia , Animais , Arabidopsis/efeitos dos fármacos , Proteínas de Arabidopsis/genética , Transporte Biológico/efeitos dos fármacos , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Flores/efeitos dos fármacos , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Proteínas de Domínio MADS/metabolismo , Modelos Biológicos , Mutação/genética , Fenótipo , Brotos de Planta/efeitos dos fármacos , Brotos de Planta/crescimento & desenvolvimento , Fatores de Tempo , Xenopus , Xilema/metabolismo
4.
Chemistry ; : e202401922, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38897920

RESUMO

The confinement and high utilization of sulfur in the cathodes is critical for improved cycling performance of lithium-sulfur batteries. In this case one-pot hydrothermal strategy is developed to produce rGO/MXene/sulfur composite aerogels where sulfur is in situ trapped in the 3D rGO/MXene conductive skeleton. The optimized composite aerogels as free-standing cathodes delivery a specific capacity of 951 mAhg-1 after 100 cycles at 0.2 C with a low fading rate of 0.062% per cycle. The excellent cycling performance is correlated with highly oxidized MXene and in situ formed sulfate/thiosulfate complex layer in the long-term cycles.

5.
Cell ; 138(6): 1184-94, 2009 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-19766570

RESUMO

Ions serve as essential nutrients in higher plants and can also act as signaling molecules. Little is known about how plants sense changes in soil nutrient concentrations. Previous studies showed that T101-phosphorylated CHL1 is a high-affinity nitrate transporter, whereas T101-dephosphorylated CHL1 is a low-affinity transporter. In this study, analysis of an uptake- and sensing-decoupled mutant showed that the nitrate transporter CHL1 functions as a nitrate sensor. Primary nitrate responses in CHL1T101D and CHLT101A transgenic plants showed that phosphorylated and dephosphorylated CHL1 lead to a low- and high-level response, respectively. In vitro and in vivo studies showed that, in response to low nitrate concentrations, protein kinase CIPK23 can phosphorylate T101 of CHL1 to maintain a low-level primary response. Thus, CHL1 uses dual-affinity binding and a phosphorylation switch to sense a wide range of nitrate concentrations in the soil, thereby functioning as an ion sensor in higher plants. For a video summary of this article, see the PaperFlick file with the Supplemental Data available online.


Assuntos
Proteínas de Transporte de Ânions/metabolismo , Arabidopsis/metabolismo , Nitratos/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas , Fosforilação , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo
6.
BMC Urol ; 24(1): 81, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589861

RESUMO

OBJECTIVE: To observe the safety and short-term outcomes of a new way of laparoscopic trocar placement in pediatric robotic-assisted Lich-Gregoir ureteral reimplantation for vesicoureteral reflux. METHODS: The retrospective study included 32 patients under 14 years diagnosed with primary vesicoureteral reflux (VUR). All these patients underwent robotic-assisted Lich-Gregoir ureteral reimplantation in our department from December 2020 to August 2022. These patients were divided into the following groups according to the different ways of trocar placement: 13 patients in group single-port plus one (SR) and 19 patients in group multiple-port (MR). Patients' characteristics as well as their perioperative and follow-up data were collected and evaluated. RESULTS: There was no significant difference in the data regarding patients' characteristics and preoperative data. These data included the grade of vesicoureteral reflux according to the voiding cystourethrogram (VCUG), and the differential degree of renal function (DRF) at the following time points: preoperative, postoperative, and comparison of preoperative and postoperative. There was no difference between the two groups. During surgery, the time of artificial pneumoperitoneum establishment, ureteral reimplantation time, and total operative time in the SR group were longer than those in the MR group. Yet only the time of artificial pneumoperitoneum establishment shows a statistical difference (P < 0.0001). Also, the peri-operative data, including the volume of blood loss, fasting time, hospitalization, and length of time that a ureteral catheter remained in place, and the number of postoperative complications demonstrate no difference. In addition, the SFU grade and VCUG grade at the following time point also show no difference between the two groups. CONCLUSION: The study demonstrates that SR in robotic-assisted Lich-Gregoir ureteral reimplantation has reached the same surgical effects as MR. In addition, the single-port plus one trocar placement receives a higher cosmetic satisfaction score from parents and did not increase the surgical time and complexity.


Assuntos
Laparoscopia , Procedimentos Cirúrgicos Robóticos , Ureter , Refluxo Vesicoureteral , Criança , Humanos , Refluxo Vesicoureteral/cirurgia , Estudos Retrospectivos , Procedimentos Cirúrgicos Urológicos , Resultado do Tratamento , Ureter/cirurgia , Reimplante
7.
Biochem Biophys Res Commun ; 681: 106-110, 2023 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-37774567

RESUMO

The global incidence of pancreatic cancer is associated with a high mortality rate and one of the lowest survival rates among all types of cancer. The clinical management modalities for pancreatic cancer encompass surgical intervention, chemotherapy, radiation therapy, targeted therapy, immunotherapy, or a combination thereof. Nevertheless, the diagnosis of pancreatic cancer often occurs at an advanced stage, thereby restricting treatment options and diminishing the prospects of achieving a cure. The cGAS-STING pathway has emerged as a potential target for antitumor therapy due to its role in promoting immune responses against cancer cells. Activation of the cGAS-STING pathway in tumor cells can lead to the production of pro-inflammatory cytokines and type I interferons, which can enhance the recruitment and activation of immune cells to the tumor microenvironment. The cGAS protein was detected in only a half of tumor tissues in pancreatic cancer patients and the underlying mechanism is still elusive. In this study, we have identified the E3 ligase DTX3L as a key regulator of cGAS-STING signaling in pancreatic cancer cells by mediating the ubiquitination and degradation of cGAS. The expression levels of DTX3L were found to be upregulated in pancreatic tumor tissues and correlated with a poor prognosis for patients with pancreatic cancer. Silencing of DTX3L resulted in enhanced activation of the cGAS-STING signaling pathway and improved antitumor immunity for pancreatic cancer, suggesting that targeting the DTX3L-cGAS axis could hold promise for the treatment of this disease.


Assuntos
Nucleotidiltransferases , Neoplasias Pancreáticas , Ubiquitina-Proteína Ligases , Humanos , Nucleotidiltransferases/genética , Pâncreas , Neoplasias Pancreáticas/terapia , Microambiente Tumoral , Ubiquitina-Proteína Ligases/genética , Ubiquitinação , Neoplasias Pancreáticas
8.
Ophthalmology ; 130(1): 111-119, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36652194

RESUMO

PURPOSE: To investigate the extent of iris trabecular contact (ITC) measured by anterior segment OCT (AS-OCT) and its association with primary angle-closure (PAC) and PAC glaucoma (PACG) in eyes with gonioscopic angle-closure and to determine the diagnostic performance of ITC for detection of gonioscopic angle-closure. DESIGN: Multicenter, prospective study. PARTICIPANTS: A total of 119 healthy participants with gonioscopic open-angle and 170 patients with gonioscopic angle-closure (94 with PAC suspect and 76 with PAC/PACG) were included. METHODS: One eye of each subject was randomly selected for AS-OCT imaging. Angle-opening distance (AOD500) and trabecular iris space area (TISA500) were measured every 10° for 360°. Two criteria of ITC500 were examined: (1) AOD500 = 0 mm and (2) TISA500 = 0 mm2. The association between the extent of ITC500 and PAC/PACG in eyes with gonioscopic angle-closure was analyzed with logistic regression analysis. MAIN OUTCOME MEASURES: Sensitivity and specificity of ITC500 for detection of gonioscopic angle-closure; odds ratio (OR) of PAC/PACG. RESULTS: The sensitivity of ITC500 ≥ 10° for detection of gonioscopic angle-closure ranged from 82.4% (AOD500 = 0 mm) to 84.7% (TISA500 = 0 mm2), and the specificity was 85.7% (for both AOD500 = 0 mm and TISA500 = 0 mm2). The extent of ITC500 determined by AS-OCT, not cumulative gonioscopy score (i.e., the sum of the modified Shaffer grades over 4 quadrants), was associated with the odds of PAC/PACG in eyes with gonioscopic angle-closure; the odds of PAC/PACG increased by 5% for every 10° increase in ITC500 (OR, 1.051, 95% confidence interval [CI], 1.022-1.080 for AOD500 = 0 mm; OR, 1.049, 95% CI, 1.022-1.078 for TISA500 = 0 mm2). Axial length and anterior chamber depth were not associated with PAC/PACG in eyes with gonioscopic angle-closure (P ≥ 0.574). CONCLUSIONS: A greater extent of ITC measured by AS-OCT, not angle-closure determined by gonioscopy, was associated with a greater odds of PAC/PACG in eyes with gonioscopic angle-closure.


Assuntos
Segmento Anterior do Olho , Glaucoma de Ângulo Fechado , Humanos , Gonioscopia , Estudos Prospectivos , Pressão Intraocular , Tomografia de Coerência Óptica/métodos , Iris , Glaucoma de Ângulo Fechado/diagnóstico
9.
Metabolomics ; 19(4): 32, 2023 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-36997715

RESUMO

INTRODUCTION: Acute ischemic stroke (AIS) accounts for the majority of all stroke, globally the second leading cause of death. Due to its rapid development after onset, its early diagnosis is crucial. OBJECTIVES: We aim to identify potential highly reliable blood-based biomarkers for early diagnosis of AIS using quantitative plasma lipid profiling via a machine learning approach. METHODS: Lipidomics was used for quantitative plasma lipid profiling, based on ultra-performance liquid chromatography tandem mass spectrometry. Our samples were divided into a discovery and a validation set, each containing 30 AIS patients and 30 health controls (HC). Differentially expressed lipid metabolites were screened based on the criteria VIP > 1, p < 0.05, and fold change > 1.5 or < 0.67. The least absolute shrinkage and selection operator (LASSO) and random forest algorithms in machine learning were used to select differential lipid metabolites as potential biomarkers. RESULTS: Three key differential lipid metabolites, CarnitineC10:1, CarnitineC10:1-OH and Cer(d18:0/16:0), were identified as potential biomarkers for early diagnosis of AIS. The former two, associated with thermogenesis, were down-regulated, whereas the latter, associated with necroptosis and sphingolipd metabolism, was upregulated. Univariate and multivariate logistic regressions showed that these three lipid metabolites and the resulting diagnostic model exhibited a strong ability in discriminating between AIS patients and HCs in both the discovery and validation sets, with an area under the curve above 0.9. CONCLUSIONS: Our work provides valuable information on the pathophysiology of AIS and constitutes an important step toward clinical application of blood-based biomarkers for diagnosing AIS.


Assuntos
AVC Isquêmico , Lipidômica , Humanos , Metabolômica , Biomarcadores , Diagnóstico Precoce , Lipídeos
10.
J Biomed Sci ; 30(1): 57, 2023 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-37517995

RESUMO

BACKGROUND: Supplemental oxygen impairs lung development in newborn infants with respiratory distress. Lactobacillus johnsonii supplementation attenuates respiratory viral infection in mice and exhibits anti-inflammatory effects. This study investigated the protective effects of intranasal administration of L. johnsonii on lung development in hyperoxia-exposed neonatal mice. METHODS: Neonatal C57BL/6N mice were reared in either room air (RA) or hyperoxia condition (85% O2). From postnatal days 0 to 6, they were administered intranasal 10 µL L. johnsonii at a dose of 1 × 105 colony-forming units. Control mice received an equal volume of normal saline (NS). We evaluated the following four study groups: RA + NS, RA + probiotic, O2 + NS, and O2 + probiotic. On postnatal day 7, lung and intestinal microbiota were sampled from the left lung and lower gastrointestinal tract, respectively. The right lung of each mouse was harvested for Western blot, cytokine, and histology analyses. RESULTS: The O2 + NS group exhibited significantly lower body weight and vascular density and significantly higher mean linear intercept (MLI) and lung cytokine levels compared with the RA + NS and RA + probiotic groups. At the genus level of the gut microbiota, the O2 + NS group exhibited significantly higher Staphylococcus and Enterobacter abundance and significantly lower Lactobacillus abundance compared with the RA + NS and RA + probiotic groups. Intranasal L. johnsonii treatment increased the vascular density, decreased the MLI and cytokine levels, and restored the gut microbiota in hyperoxia-exposed neonatal mice. CONCLUSIONS: Intranasal administration of L. johnsonii protects against hyperoxia-induced lung injury and modulates the gut microbiota.


Assuntos
Microbioma Gastrointestinal , Hiperóxia , Lactobacillus johnsonii , Lesão Pulmonar , Ratos , Animais , Camundongos , Hiperóxia/complicações , Hiperóxia/patologia , Animais Recém-Nascidos , Lesão Pulmonar/prevenção & controle , Lesão Pulmonar/patologia , Ratos Sprague-Dawley , Administração Intranasal , Camundongos Endogâmicos C57BL , Pulmão/patologia , Citocinas
11.
Immunol Invest ; 52(5): 546-560, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37154418

RESUMO

BACKGROUND: Apoptosis, inflammation, and the extracellular matrix (ECM) synthesis and catabolism are compromised with intervertebral disc degeneration (IDD). Ginkgetin (GK) has been demonstrated to alleviate several diseases; however, its effect on IDD remains unknown. METHODS: The nucleus pulposus cells (NPCs) were stimulated with interleukin (IL)-1ß to construct the IDD models in vitro. Rats were used for the construction of the IDD models in vivo via the fibrous ring puncture method. The effect and mechanism of GK on IDD were determined by cell counting kit-8 (CCK-8), flow cytometry, western blot, real-time quantitative polymerase chain reaction (RT-qPCR), enzyme­linked immunosorbent assay (ELISA), hematoxylin and eosin (HE) and safranine O staining, and immunohistochemistry (IHC) assays, respectively. RESULTS: GK increased the cell viability and upregulated the expressions of anti-apoptosis and ECM synthesis markers in NPCs treated with IL-1ß. GK also decreased apoptosis rate, and downregulated the expressions of proteins related to pro-apoptosis, ECM catabolism, and inflammation in vitro. Mechanically, GK reduced the expression of nucleotide binding oligomeric domain like receptor protein 3 (NLRP3) inflammasome-related proteins. Overexpression of NLRP3 reversed the effect of GK on the proliferation, apoptosis, inflammation, and ECM degradation in IL-1ß-induced NPCs. Moreover, GK attenuated the pathological manifestations, inflammation, ECM degradation, and NLRP3 inflammasome expression in IDD rats. CONCLUSION: GK suppressed apoptosis, inflammation, and ECM degradation to alleviate IDD via the inactivation of NLRP3 inflammasome.


Assuntos
Inflamassomos , Degeneração do Disco Intervertebral , Ratos , Animais , Inflamassomos/metabolismo , Degeneração do Disco Intervertebral/tratamento farmacológico , Degeneração do Disco Intervertebral/metabolismo , Degeneração do Disco Intervertebral/patologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Inflamação/metabolismo , Matriz Extracelular/metabolismo
12.
Environ Res ; 224: 115393, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-36740153

RESUMO

Saline and alkaline soils are a challenge for sustainable crop production. The use of organic and inorganic amendments is a common practice to increase the fertility of salt-affected soils that can trigger faster carbon (C) and nitrogen (N) cycling. We examined the effects of gypsum (Gyps), farm manure (Manure) and rice straw (Straw) on enzyme activities, organic matter mineralization and CO2 emissions in two salt-affected soils [Solonchak (saline); pH: 8, electrical conductivity (EC): 6.5, sodium adsorption ratio (SAR): 2.5, and Solonetz (alkaline sodic); pH: 8.9, EC: 1.6, SAR: 17]. Gypsum addition decreased soil pH up to 0.62 and 0.30 units, SAR 1.2 and 5.2 units, and EC 2.9 and 1.4 units in Solonchak and Solonetz, respectively. Dissolved organic C, microbial biomass C, dissolved organic N, mineral N (NO3- and NH4+), enzyme activities (urease, invertase, catalase, phosphatase, phenol-oxidase), alkali extractable phenols, and available phosphorous increased with the application of all amendments in both soils. Solonetz released more CO2 than Solonchak, whereas maximum CO2 emissions were common after manure application (3140 mg kg-1 in Solonchak, and 3890 mg kg-1 in Solonetz). We conclude that high SAR and low EC increase CO2 emissions through accelerated C and N cycling and manure decomposition in Solonetz soils.


Assuntos
Oryza , Solo , Solo/química , Sulfato de Cálcio , Esterco , Dióxido de Carbono , Cloreto de Sódio , Carbono
13.
Int J Med Sci ; 20(11): 1377-1385, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37790845

RESUMO

Background: 22q11.2 deletion syndrome (22q11.2DS) is a microdeletion syndrome exhibiting significant clinical phenotype variability. This study aimed to investigate the clinical features, immune profiles, and cognitive abilities of 22q11.2DS patients receiving treatment at MacKay Memorial Hospital in Taipei, Taiwan. Methods: This is a cross-sectional analysis between January 2001 and December 2022. We recruited 27 patients with 22q11.2DS using fluorescence in situ hybridization (FISH), multiplex ligation-dependent probe amplification (MLPA) and array comparative genomic hybridization (aCGH). Our evaluation included patient history, physical examination, laboratory analysis, and cardiac and cognitive assessment. Results: We included 27 patients with 22q11.2DS, 7 (25.9%) of whom were female. The median age of the patients was 17.9 yr. Ninety-three percent of the patients exhibited the characteristic facial features associated with the syndrome. A family history of 22q11.2DS was found in 11.1% of the patients. Furthermore, 74.1% of the patients had a congenital heart defect, the most common of which was tetralogy of Fallot (40.7%). Hypocalcemia was observed in 40.7% of the patients. A low T-cell count was observed in 66.7% of the patients, whereas 18.5% had low immunoglobulin levels. Cognitive assessments revealed that four out of six evaluated patients (66.7%) had an intellectual disability, as evidenced by intellectual quotient scores less than 70. The remaining two patients (33.3%) had a borderline intellectual function. Conclusion: Tetralogy of Fallot, hypocalcemia, immunologic defects, and cognitive impairment were common among our patients. To address the potential multisystem involvement, we recommend that all affected individuals undergo a comprehensive evaluation by a multidisciplinary care team.


Assuntos
Síndrome de DiGeorge , Cardiopatias Congênitas , Hipocalcemia , Tetralogia de Fallot , Humanos , Feminino , Masculino , Síndrome de DiGeorge/genética , Síndrome de DiGeorge/diagnóstico , Tetralogia de Fallot/genética , Hipocalcemia/genética , Hibridização in Situ Fluorescente , Taiwan/epidemiologia , Estudos Transversais , Hibridização Genômica Comparativa , Cardiopatias Congênitas/genética , Sistema Imunitário , Deleção Cromossômica
14.
J Comput Assist Tomogr ; 47(2): 291-300, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36723407

RESUMO

OBJECTIVES: This study aimed to explore the diagnostic ability of apparent diffusion coefficient (ADC) values obtained from different region of interest (ROI) measurements in tumor parenchyma for differentiating posterior fossa tumors (PFTs) and the correlations between ADC values and Ki-67. METHODS: Seventy-three pediatric patients with PFTs who underwent conventional diffusion-weighted imaging were recruited in this study. Five different ROIs were manually drawn by 2 radiologists (ROI-polygon, ROI-3 sections, ROI-3-5 ovals, ROI-more ovals, and ROI-whole). The interreader/intrareader repeatability, time required, diagnostic ability, and Ki-67 correlation analysis of the ADC values based on these ROI strategies were calculated. RESULTS: Both interreader and intrareader reliabilities were excellent for ADC values among the different ROI strategies (intraclass correlation coefficient, 0.899-0.992). There were statistically significant differences in time consumption among the 5 ROI selection methods ( P < 0.001). The time required for the ROI-3-5 ovals was the shortest (32.23 ± 5.14 seconds), whereas the time required for the ROI-whole was the longest (204.52 ± 92.34 seconds). The diagnostic efficiency of the ADC values showed no significant differences among the different ROI measurements ( P > 0.05). The ADC value was negatively correlated with Ki-67 ( r = -0.745 to -0.798, all P < 0.0001). CONCLUSIONS: The ROI-3-5 ovals method has the best interobserver repeatability, the shortest amount of time spent, and the best diagnostic ability. Thus, it is considered an effective measurement to produce ADC values in the evaluation of pediatric PFTs.


Assuntos
Neoplasias Encefálicas , Imagem de Difusão por Ressonância Magnética , Humanos , Criança , Reprodutibilidade dos Testes , Antígeno Ki-67 , Variações Dependentes do Observador , Estudos Retrospectivos , Imagem de Difusão por Ressonância Magnética/métodos , Neoplasias Encefálicas/diagnóstico por imagem
15.
BMC Pregnancy Childbirth ; 23(1): 387, 2023 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-37237335

RESUMO

BACKGROUND: Platelet parameters during pregnancy were associated with the risk of preeclampsia (PE), but the predictive value of these parameters for PE remained unclear. Our aim was to clarify the individual and incremental predictive value of platelet parameters, including platelet count (PC), mean platelet volume (MPV), plateletcrit (PCT), and platelet distribution width (PDW) for PE. METHODS: This study was based on the Born in Guangzhou Cohort Study in China. Data on platelet parameters were extracted from medical records of routine prenatal examinations. Receiver operating characteristic (ROC) curve was performed to analyze the predictive ability of platelet parameters for PE. Maternal characteristic factors proposed by NICE and ACOG were used to develop the base model. Detection rate (DR), integrated discrimination improvement (IDI) and continuous net reclassification improvement (NRI) were calculated compared with the base model to assess the incremental predictive value of platelet parameters. RESULTS: A total of 30,401 pregnancies were included in this study, of which 376 (1.24%) were diagnosed with PE. Higher levels of PC and PCT were observed at 12-19 gestational weeks in women who developed PE later. However, no platelet parameters before 20 weeks of gestation reliably distinguished between PE complicated pregnancy and non-PE complicated pregnancy, with all values of the areas under the ROC curves (AUC) below 0.70. The addition of platelet parameters at 16-19 gestational weeks to the base model increased the DR for preterm PE from 22.9 to 31.4% at a fixed false positive rate of 5%, improved the AUC from 0.775 to 0.849 (p = 0.015), and yielded a NRI of 0.793 (p < 0.001), and an IDI of 0.0069 (p = 0.035). Less but significant improvement in prediction performance was also observed for term PE and total PE when all the four platelet parameters were added to the base model. CONCLUSIONS: Although no single platelet parameter at the early stage of pregnancy identified PE with high accuracy, the addition of platelet parameters to known independent risk factors could improve the prediction of PE.


Assuntos
Pré-Eclâmpsia , Gravidez , Recém-Nascido , Feminino , Humanos , Pré-Eclâmpsia/diagnóstico , Estudos de Coortes , Estudos Prospectivos , Contagem de Plaquetas , Volume Plaquetário Médio
16.
Pediatr Cardiol ; 44(6): 1262-1270, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37029813

RESUMO

We investigated the hemodynamic parameters of pediatric PDA patients and focused on the influence of PDA size on pulmonary arterial pressure and the prevalence of pulmonary hypertension. A total of 52 patients aged between 2 months and 20 years who received transcatheter closure of a PDA from January 2018 to June 2022 in our institution were retrospectively recruited. Their hemodynamic parameters collected both by echocardiography and by cardiac catheterization were analyzed to delineate the influence of PDA size on the pulmonary vascular system. The echocardiographic-based ductal size and indexed PDA size were 1.93 mm (1.15-6 mm) and 4.05 mm/m2 (2.03-25.47 mm/m2), respectively. The pulmonary artery pressure measured was 20.83 mmHg (8-45 mmHg). We found a positive correlation between indexed PDA size and mean pulmonary arterial pressure (mPAP) (Pearson correlation coefficient = 0.47, p < 0.001). A subgroup analysis showed that 28 patients (53.8%) developed pulmonary hypertension (PH) (defined as mPAP > 20 mmHg). The median age of the PH group was 1.02 years [range: 0.19-8.64], which was significantly younger than the non-PH group's median age of 3.43 years [range: 0.42-19.96] (p = 0.001). The indexed PDA size for the PH group, 4.69 mm/m2, was significantly higher than that of the non-PH group, 3.2 mm/m2 (p = 0.004). The major risk factor for patients with PH was the PDA/BSA index, with an OR of 2.181 (95% CI, 1.224-3.887). Our demographic data showed younger patients with a higher PDA/BSA index are more likely to develop pulmonary hypertension.


Assuntos
Permeabilidade do Canal Arterial , Hipertensão Pulmonar , Criança , Humanos , Lactente , Pré-Escolar , Permeabilidade do Canal Arterial/diagnóstico por imagem , Permeabilidade do Canal Arterial/complicações , Hipertensão Pulmonar/etiologia , Resultado do Tratamento , Estudos Retrospectivos , Hemodinâmica , Ecocardiografia , Cateterismo Cardíaco/efeitos adversos
17.
Sensors (Basel) ; 23(1)2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36617071

RESUMO

The line width of different line shapes is a very important parameter in absorption spectroscopy sensing techniques. Based on the high sensitivity and low noise properties of wavelength modulation spectroscopy, we report a novel line width measurement method. After theoretically proving the relationship between line width, modulation amplitude and the amplitude of the second harmonic at the center frequency, the absorption lines of CH4 near 6046.96 cm-1 and CO2 4989.97 cm-1 were chosen for simulation, and the relative errors of the line width between our method and theoretical data were kept at about 1%. A distributed feedback laser diode operating near 1653 nm with three different concentrations of CH4 was used for experimental validation, and the results were consistent with the numerical simulation. Additionally, since only the peaks of second harmonic need to be measured, the advantages of wavelength modulation can be utilized while reducing the difficulty of data acquisition.

18.
J Environ Manage ; 344: 118453, 2023 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-37354585

RESUMO

Additives were widely investigated to retain the nutrients and mitigate the greenhouse gas emissions (GHGs) during manure composting. However, the sustained effects of additives on the GHGs emissions following incorporation of composts to soil were scarcely explored. This study evaluated the effects of bentonite added at the beginning of pig manure composting on the GHGs emissions during two successive processes, i.e., composting and soil incubation amended with composting products. Addition of bentonite did not hinder the composting process and alter the total CO2 emission. On the other hand, reduction by about 17% and 29% for CH4 and N2O emission, respectively, was achieved in the presence of bentonite during composting. Incorporation of the final composting products to soil enhanced significantly the soil C and N of various forms, and gas emissions of CO2 and N2O. However, no significant differences were observed between bentonite-manure co-compost and manure-only compost application except for the N2O emission. Compared to the manure-only compost, compost amended with bentonite reduced N2O loss by around 6.8%, but not statistically significant. This study confirmed that addition of bentonite at the composting stage can mitigate the GHGs emission considering both composting and compost application stages, with all reductions occurring at the composting stage.


Assuntos
Compostagem , Gases de Efeito Estufa , Animais , Suínos , Gases de Efeito Estufa/análise , Bentonita , Esterco , Dióxido de Carbono/análise , Nitrogênio/análise , Metano/análise , Solo , Óxido Nitroso/análise
19.
BMC Genomics ; 23(1): 41, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-35012443

RESUMO

BACKGROUND: The early death and health problems of calves caused substantial economic losses in the dairy industry. As the immune system of neonates has not been fully developed, the absorption of maternal immunoglobulin (Ig) from colostrum is essential in protecting newborn calves against common disease organisms in their early life. The overwhelming majority of Ig in bovine whey is transported from the serum. Therefore, Ig concentration in the colostrum and serum of dairy cows are critical traits when estimating the potential disease resistance of its offspring. RESULTS: Colostrum, blood, and hair follicle samples were collected from 588 Chinese Holstein cows within 24 h after calving. The concentration of total IgG, IgG1, IgG2, IgA and IgM in both colostrum and serum were detected via ELISA methods. With GCTA software, genome-wide association studies (GWASs) were performed with 91,620 SNPs genotyped by GeneSeek 150 K (140,668 SNPs) chips. As a result, 1, 5, 1 and 29 significant SNPs were detected associated with the concentrations of colostrum IgG1, IgG2, IgA IgM, and serum IgG2 at the genome-wide level (P < 3.08E-6); 11, 2, 13, 2, 12, 8, 2, 27, 1 and 4 SNPs were found significantly associated with total IgG, IgG1, IgG2, IgA and IgM in colostrum and serum at the suggestive level (P < 6.15E-5). Such SNPs located in or proximate to (±1 Mb) 423 genes, which were functionally implicated in biological processes and pathways, such as immune response, B cell activation, inflammatory response and NF-kappaB signaling pathways. By combining the biological functions and the known QTL data for immune traits in bovine, 14 promising candidate functional genes were identified for immunoglobulin concentrations in colostrum and serum in dairy cattle, they were FGFR4, FGFR2, NCF1, IKBKG, SORBS3, IGHV1S18, KIT, PTGS2, BAX, GRB2, TAOK1, ICAM1, TGFB1 and RAC3. CONCLUSIONS: In this study, we identified 14 candidate genes related to concentrations of immunoglobulins in colostrum and serum in dairy cattle by performing GWASs. Our findings provide a groundwork for unraveling the key genes and causal mutations affecting immunoglobulin concentrations in colostrum and important information for genetic improvement of such traits in dairy cattle.


Assuntos
Colostro , Estudos de Associação Genética/veterinária , Animais , Animais Recém-Nascidos , Bovinos , China , Indústria de Laticínios , Feminino , Imunoglobulina G , Gravidez
20.
Anal Chem ; 94(41): 14290-14298, 2022 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-36198125

RESUMO

We propose to replace the traditional time-frequency domain filtering with feature domain filtering to realize an innovation of filtering algorithm. A feature domain transform filter (FDTF) is composed of the feature domain transform layer based on principal component analysis (PCA) algorithm, the feature domain information extractor based on deep learning and the time domain transform layer. It is established to filter out the noise with the same frequency and phase as the signal and is verified on methane gas. Although FDTF is established based on the simulated data set, the filtering effects of the simulation test set and the experimental data set show that the proposed FDTF outperforms other widely used time-frequency filtering algorithms. The FDTF-assisted methane sensor has good linearity at different concentrations of methane gas. With the FDTF enhancement, the optimized methane sensor performs excellent precision and stability in real-time measurements and achieves the minimum detectable column density of 2.50 ppm·m. This is undoubtedly a successful attempt to move the signal to a new domain for parsing and separation.


Assuntos
Algoritmos , Metano , Simulação por Computador , Análise de Componente Principal , Processamento de Sinais Assistido por Computador , Razão Sinal-Ruído
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