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1.
Elife ; 132024 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-39360693

RESUMO

The extracellular matrix plays an integrative role in cellular responses in plants, but its contribution to the signalling of extracellular ligands largely remains to be explored. Rapid alkalinisation factors (RALFs) are extracellular peptide hormones that play pivotal roles in various physiological processes. Here, we address a crucial connection between the de-methylesterification machinery of the cell wall component pectin and RALF1 activity. Pectin is a polysaccharide, contributing to the structural integrity of the cell wall. Our data illustrate that the pharmacological and genetic interference with pectin methyl esterases (PMEs) abolishes RALF1-induced root growth repression. Our data suggest that positively charged RALF1 peptides bind negatively charged, de-methylesterified pectin with high avidity. We illustrate that the RALF1 association with de-methylesterified pectin is required for its FERONIA-dependent perception, contributing to the control of the extracellular matrix and the regulation of plasma membrane dynamics. Notably, this mode of action is independent of the FER-dependent extracellular matrix sensing mechanism provided by FER interaction with the leucine-rich repeat extensin (LRX) proteins. We propose that the methylation status of pectin acts as a contextualizing signalling scaffold for RALF peptides, linking extracellular matrix dynamics to peptide hormone-mediated responses.


Assuntos
Arabidopsis , Hidrolases de Éster Carboxílico , Pectinas , Transdução de Sinais , Hidrolases de Éster Carboxílico/metabolismo , Hidrolases de Éster Carboxílico/genética , Pectinas/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Arabidopsis/crescimento & desenvolvimento , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Raízes de Plantas/metabolismo , Raízes de Plantas/crescimento & desenvolvimento , Parede Celular/metabolismo , Matriz Extracelular/metabolismo
2.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 38(7): 801-806, 2024 Jul 15.
Artigo em Chinês | MEDLINE | ID: mdl-39013815

RESUMO

Objective: To investigate the benefits and drawbacks of breast reconstruction with endoscopic-assisted harvesting of the latissimus dorsi muscle flap for breast cancer and treatment experience of postoperative operation-related complications. Methods: A retrospective analysis was performed on clinical data of 26 female patients with breast cancer who met the selection criteria between September 2021 and March 2023 aging 48.7 years (range, 26-69 years). All tumors were unilateral, with 17 on the left side and 9 on the right side. The tumor size ranged from 1.0 to 7.0 cm, with an average of 2.7 cm. The pathological staging included T 1 in 11 cases, T 2 in 14 cases, and T 3 in 1 case; N 0 in 10 cases, N 1 in 11 cases, N 2 in 2 cases, and N 3 in 3 cases; no distant metastasis (M 0) occurred when first diagnosed. Among them, 10 cases underwent breast conserving surgery, and 16 cases underwent nipple-sparing mastectomy. All patients underwent breast reconstruction with endoscopic-assisted harvesting of the latissimus dorsi muscle flap. The operation time, incision length, and postoperative drainage volume in 3 days were recorded. Breast-Q "Satisfaction with back" scale was conducted to evaluate patients' satisfaction with back at 6 months after operation. Results: The operation time was 280-480 minutes (mean, 376.7 minutes), the incision length was 10-15 cm (mean, 12.2 cm), the postoperative drainage volume in 3 days was 500-1 600 mL (mean, 930.2 mL). There were 4 cases of postoperative seroma, 1 case of incision rupture, 1 case of paresthesia of the thoracic wall, and 1 case of edema of the ipsilateral upper limb. All patients were followed up 12-30 months (mean, 20.1 months). No latissimus dorsi muscle flap necrosis, latissimus dorsi muscle atrophy, or shoulder joint dysfunction occurred during follow-up; 2 patients had recurrence of lymph nodes in the ipsilateral axilla after operation, but no distant metastasis occurred. Breast-Q score at 6 months after operation was 64-100 (mean, 79.5). The average score was 78.6 (range, 64-100) in patients underwent nipple-sparing mastectomy and 81.0 (range, 78-100) in patients underwent breast conserving surgery. Conclusion: Breast reconstruction with endoscopic-assisted harvesting of the latissimus dorsi muscle flap for breast cancer is proven to be a surgical approach with safety and cosmetic effects with mild postoperative operation-related complications and considerable patient satisfaction.


Assuntos
Neoplasias da Mama , Endoscopia , Mamoplastia , Complicações Pós-Operatórias , Músculos Superficiais do Dorso , Retalhos Cirúrgicos , Humanos , Feminino , Pessoa de Meia-Idade , Neoplasias da Mama/cirurgia , Neoplasias da Mama/patologia , Mamoplastia/métodos , Adulto , Estudos Retrospectivos , Músculos Superficiais do Dorso/transplante , Endoscopia/métodos , Idoso , Mastectomia/métodos , Mastectomia Segmentar/métodos
3.
Front Oncol ; 14: 1403522, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39055558

RESUMO

Purpose: To construct and validate radiomics models that utilize ultrasound (US) and digital breast tomosynthesis (DBT) images independently and in combination to non-invasively predict the Ki-67 status in breast cancer. Materials and methods: 149 breast cancer women who underwent DBT and US scans were retrospectively enrolled from June 2018 to August 2023 in total. Radiomics features were acquired from both the DBT and US images, then selected and reduced in dimensionality using several screening approaches. Establish radiomics models based on DBT, and US separately and combined. The area under the receiver operating characteristic curve (AUC), accuracy, specificity, and sensitivity were utilized to validate the predictive ability of the models. The decision curve analysis (DCA) was used to evaluate the clinical applicability of the models. The output of the classifier with the best AUC performance was converted into Rad-score and was regarded as Rad-Score model. A nomogram was constructed using the logistic regression method, integrating the Rad-Score and clinical factors. The model's stability was assessed through AUC, calibration curves, and DCA. Results: Support vector machine (SVM), logistic regression (LR), and random forest (RF) were trained to establish radiomics models with the selected features, with SVM showing optimal results. The AUC values for three models (US_SVM, DBT_SVM, and merge_SVM) were 0.668, 0.704, and 0.800 respectively. The DeLong test indicated a notable disparity in the area under the curve (AUC) between merge_SVM and US_SVM (p = 0.048), while there was no substantial variability between merge_SVM and DBT_SVM (p = 0.149). The DCA curve indicates that merge_SVM is superior to unimodal models in predicting high Ki-67 level, showing more clinical values. The nomogram integrating Rad-Score with tumor size obtained the better performance in test set (AUC: 0.818) and had more clinical net. Conclusion: The fusion radiomics model performed better in predicting the Ki-67 expression level of breast carcinoma, but the gain effect is limited; thus, DBT is preferred as a preoperative diagnosis mode when resources are limited. Nomogram offers predictive advantages over other methods and can be a valuable tool for predicting Ki-67 levels in BC.

4.
J Appl Clin Med Phys ; 25(8): e14450, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39031891

RESUMO

The purpose of this study is to develop an electronic portal imaging device-based multi-leaf collimator calibration procedure using log files. Picket fence fields with 2-14 mm nominal strip widths were performed and normalized by open field. Normalized pixel intensity profiles along the direction of leaf motion for each leaf pair were taken. Three independent algorithms and an integration method derived from them were developed according to the valley value, valley area, full-width half-maximum (FWHM) of the profile, and the abutment width of the leaf pairs obtained from the log files. Three data processing schemes (Scheme A, Scheme B, and Scheme C) were performed based on different data processing methods. To test the usefulness and robustness of the algorithm, the known leaf position errors along the direction of perpendicular leaf motion via the treatment planning system were introduced in the picket fence field with nominal 5, 8, and 11 mm. Algorithm tests were performed every 2 weeks over 4 months. According to the log files, about 17.628% and 1.060% of the leaves had position errors beyond ± 0.1 and ± 0.2 mm, respectively. The absolute position errors of the algorithm tests for different data schemes were 0.062 ± 0.067 (Scheme A), 0.041 ± 0.045 (Scheme B), and 0.037 ± 0.043 (Scheme C). The absolute position errors of the algorithms developed by Scheme C were 0.054 ± 0.063 (valley depth method), 0.040 ± 0.038 (valley area method), 0.031 ± 0.031 (FWHM method), and 0.021 ± 0.024 (integrated method). For the efficiency and robustness test of the algorithm, the absolute position errors of the integration method of Scheme C were 0.020 ± 0.024 (5 mm), 0.024 ± 0.026 (8 mm), and 0.018 ± 0.024 (11 mm). Different data processing schemes could affect the accuracy of the developed algorithms. The integration method could integrate the benefits of each algorithm, which improved the level of robustness and accuracy of the algorithm. The integration method can perform multi-leaf collimator (MLC) quality assurance with an accuracy of 0.1 mm. This method is simple, effective, robust, quantitative, and can detect a wide range of MLC leaf position errors.


Assuntos
Algoritmos , Aceleradores de Partículas , Garantia da Qualidade dos Cuidados de Saúde , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Radioterapia de Intensidade Modulada , Planejamento da Radioterapia Assistida por Computador/métodos , Humanos , Radioterapia de Intensidade Modulada/métodos , Garantia da Qualidade dos Cuidados de Saúde/normas , Aceleradores de Partículas/instrumentação , Calibragem , Neoplasias/radioterapia
5.
Sensors (Basel) ; 24(14)2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39066024

RESUMO

In this paper, a practical discrete-time control method with adaptive image feature prediction for the image-based visual servoing (IBVS) scheme is presented. In the discrete-time IBVS inner-loop/outer-loop control architecture, the time delay caused by image capture and computation is noticed. Considering the dynamic characteristics of a 6-DOF manipulator velocity input system, we propose a linear dynamic model to describe the motion of a robot end effector. Furthermore, for better estimation of image features and smoothing of the robot's velocity input, we propose an adaptive image feature prediction method that employs past image feature data and real robot velocity data to adopt the prediction parameters. The experimental results on a 6-DOF robotic arm demonstrate that the proposed method can ensure system stability and accelerate system convergence.

6.
Heliyon ; 10(10): e31071, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38803891

RESUMO

Objective: The Obturator Functioning Scale (OFS) is a scale without formal measures of validity in any language. This study aimed to translate and adapt the OFS from English to Chinese and check its reliability and validity in Chinese-speaking patients with obturator prostheses after cancer-related maxillectomy. Methods: The 15-item Chinese preversion of the OFS was completed by 133 patients in three tertiary stomatological hospitals. Of these, 41 completed it again one week after the first measurement. The patients also completed the Chinese version of the University of Washington quality of life scale (UW-QOL, Version 4). Results: Item 12 ("upper lip feels numb") was deleted to achieve a better statistical fit. The 14-item Chinese version of the OFS (OFS-Ch) demonstrated high internal consistency (Cronbach's alpha = 0.908). The test-retest reliability coefficients for most items exceeded 0.90, indicating substantial reproducibility. Confirmatory factor analysis found that the scale consisted of three correlated factors: 1) eating (four items), 2) speech (five items), and 3) other problems (five items). This explained 70.2 % of the total variance using exploratory factor analysis. The scale was significantly convergent and discriminant and could validly discriminate between patients with Brown I and IId maxillary defects. Conclusions: Our results showed that the OFS-Ch scale is a valid tool for evaluating oral dysfunction and satisfaction with appearance for patients with the obturator prosthesis and identifying those at risk of poor obturator function in clinical settings.

7.
Sci Adv ; 10(16): eadh3425, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38630810

RESUMO

Drosophila melanogaster is a widely used model organism for studying environmental adaptation. However, the genetic diversity of populations in Asia is poorly understood, leaving a notable gap in our knowledge of the global evolution and adaptation of this species. We sequenced genomes of 292 D. melanogaster strains from various ecological settings in China and analyzed them along with previously published genome sequences. We have identified six global genetic ancestry groups, despite the presence of widespread genetic admixture. The strains from China represent a unique ancestry group, although detectable differentiation exists among populations within China. We deciphered the global migration and demography of D. melanogaster, and identified widespread signals of adaptation, including genetic changes in response to insecticides. We validated the effects of insecticide resistance variants using population cage trials and deep sequencing. This work highlights the importance of population genomics in understanding the genetic underpinnings of adaptation, an effort that is particularly relevant given the deterioration of ecosystems.


Assuntos
Drosophila melanogaster , Metagenômica , Animais , Drosophila melanogaster/genética , Variação Genética , Ecossistema , África Subsaariana , China
8.
Chem Biol Drug Des ; 103(4): e14519, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38570708

RESUMO

Kaempferol (KPR), a flavonoid compound found in various plants and foods, has garnered attention for its anti-inflammatory, antioxidant, and anticancer properties. In preliminary studies, KPR can modulate several signaling pathways involved in inflammation, making it a candidate for treating cholecystitis. This study aimed to explore the effects and mechanisms of KPR on lipopolysaccharide (LPS)-induced human gallbladder epithelial cells (HGBECs). To assess the impact of KPR on HGBECs, the HGBECs were divided into control, KPR, LPS, LPS + KPR, and LPS + UDCA groups. Cell viability and cytotoxicity were evaluated by MTT assay and lactate dehydrogenase (LDH) assay, respectively, and concentrations of KPR (10-200 µM) were tested. LPS-induced inflammatory responses in HGBECs were to create an in vitro model of cholecystitis. The key inflammatory markers (IL-1ß, IL-6, and TNF-α) levels were quantified using ELISA, The modulation of the MAPK/NF-κB signaling pathway was measured by western blot using specific antibodies against pathway components (p-IκBα, IκBα, p-p65, p65, p-JNK, JNK, p-ERK, ERK, p-p38, and p38). The cell viability and LDH levels in HGBECs were not significantly affected by 50 µM KPR, thus it was selected as the optimal KPR intervention concentration. KPR increased the viability of LPS-induced HGBECs. Additionally, KPR inhibited the inflammatory factors level (IL-1ß, IL-6, and TNF-α) and protein expression (iNOS and COX-2) in LPS-induced HGBECs. Furthermore, KPR reversed LPS-induced elevation of p-IκBα/IκBα, p-p65/p65, p-JNK/JNK, p-ERK/ERK, and p-p38/p38 ratios. KPR attenuates the LPS-induced inflammatory response in HGBECs, possibly by inhibiting MAPK/NF-κB signaling.


Assuntos
Colecistite , NF-kappa B , Humanos , NF-kappa B/metabolismo , Lipopolissacarídeos/toxicidade , Inibidor de NF-kappaB alfa/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Quempferóis/farmacologia , Transdução de Sinais , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Células Epiteliais/metabolismo , Sistema de Sinalização das MAP Quinases
9.
J AOAC Int ; 107(4): 704-713, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38492563

RESUMO

BACKGROUND: Arcae concha and Meretricis concha cyclinae concha are two marine shellfish herbs with similar composition and efficacy, which are usually calcined and used clinically. OBJECTIVE: This study investigated variations in the inorganic and organic components of Arcae concha and Meretricis concha cyclinae concha from different production regions, both Arcae concha and Meretricis concha cyclinae concha. The aim was to enhance the understanding of these two types of marine shell traditional Chinese medicine (msTCM) and provide a foundation for their future development and application. METHOD: Spectroscopic techniques, including infrared spectroscopy, X-ray spectroscopy, and X-ray fluorescence spectroscopy, were used to analyze the calcium carbonate (CaCO3) crystal and trace elements. Thermogravimetric analysis was used to investigate the decomposition process during heating. The proteins were quantified using the BCA protein assay kit. Principal component analysis (PCA) was used to classify inorganic elements in the two marine shellfish traditional Chinese medicines. RESULTS: No significant differences were found among the various production regions. The crystal structure of CaCO3 in the raw products was aragonite, but it transformed into calcite after calcination. The contents of Ca, Na, Sr, and other inorganic elements were highest. The protein content was significantly reduced after calcination. Therefore, these factors cannot accurately reflect the internal quality of TCM, rendering qualitative identification challenging. CaCO3 dissolution in the decoction of Arcae concha and Meretricis concha cyclinae concha increased after calcination, aligning with the clinical application of calcined shell TCM. PCA revealed the inorganic elements in them, indicating that the variation in trace element composition among different drugs leads to differences in their therapeutic focus, which should be considered during usage. CONCLUSIONS: This study clarifies the composition and structure changes of corrugated and clam shell before and after calcining, and it lays the foundation for the comprehensive utilization of marine traditional Chinese medicine. HIGHLIGHTS: These technical representations reveal the differences between raw materials and processed products, which will provide support for the quality control of other shellfish TCM.


Assuntos
Carbonato de Cálcio , Medicina Tradicional Chinesa , Animais , Carbonato de Cálcio/química , Carbonato de Cálcio/análise , Arcidae/química , Exoesqueleto/química , Análise de Componente Principal , Frutos do Mar/análise , Oligoelementos/análise , Oligoelementos/química
10.
Ultrason Sonochem ; 102: 106714, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38113586

RESUMO

A growing interest in the development of efficient strategies for the removal of organic pollutants from polluted water is emerging. As such, artificial micro/nano machines performing excellent water purification tasks have recently attracted more research attention of scientists. Hereby a spinous Fe3O4@PPy microrobot is presented that towards an efficient organic pollutant removal by enhancing Fenton-like reaction. The microrobot is fabricated by wrapping polypyrrole (PPy) on a spiny magnetic template prepared from sunflowers pollen. Modulating the sound pressure and frequency of the ultrasonic field enables the Fe3O4@PPy microrobot to present multimode motion, such as violent eruption-like motion caused by local cavitation (ELM), march-like unific motion (MLM), and typhoon-like rotation toward the center gathered motion (TLM). This multimode motion achieves the sufficient locomotion of microrobots in three-dimensional space and effective contact with organic pollutants in polluted water. Furthermore, a 5.2-fold increase in the degradation rate of methylene blue has been realized using Fe3O4@PPy microrobots under low-concentration hydrogen peroxide conditions. Also, the magnetically controlled recovery of microrobots from water after the completion of the degradation task has been demonstrated. The magnetic-acoustic actuated spinous microrobot can be extrapolated to other catalytic microrobot, developing a new strategy for an easier implementation and recovery of microrobot in real applications of water purification.

11.
iScience ; 26(11): 108320, 2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-38026188

RESUMO

Swimming microrobot energized by magnetic fields exhibits remotely propulsion and modulation in complex biological experiment with high precision. However, achieving high environment adaptability and multiple tasking capability in one configuration is still challenging. Here, we present a strategy that use oriented magnetized Janus spheres to assemble the microdimer robots with two magnetic distribution configurations of head-to-side configuration (HTS-config) and head-to-head configuration (HTH-config), achieving performance of multiple tasks through multimode transformation and locomotion. Modulating the magnetic frequency enables multimode motion transformation between tumbling, rolling, and swing motion with different velocities. The dual-asynchronization mechanisms of HTS-config and HTH-config robot dependent on magnetic dipole-dipole angle are investigated by molecular dynamic simulation. In addition, the microdimer robot can transport cell crossing morphological rugae or complete drug delivery on tissues by switching motion modes. This microdimer robot can provide versatile motion modes to address environmental variations or multitasking requirements.

12.
Front Bioeng Biotechnol ; 11: 1277964, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37781535

RESUMO

Micro-nano robots have emerged as a promising research field with vast potential applications in biomedicine. The motor is the key component of micro-nano robot research, and the design of the motor is crucial. Among the most commonly used motors are those derived from living cells such as bacteria with flagella, sperm, and algal cells. Additionally, scientists have developed numerous self-adaptive biomimetic motors with biological functions, primarily cell membrane functionalized micromotors. This novel type of motor exhibits remarkable performance in complex media. This paper provides a comprehensive review of the structure and performance of micro-nano robots that utilize living cells and functionalized biological cell membranes. We also discuss potential practical applications of these mirco-nano robots as well as potential challenges that may arise in future development.

13.
Cell Res ; 33(10): 745-761, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37452091

RESUMO

Since the release of the complete human genome, the priority of human genomic study has now been shifting towards closing gaps in ethnic diversity. Here, we present a fully phased and well-annotated diploid human genome from a Han Chinese male individual (CN1), in which the assemblies of both haploids achieve the telomere-to-telomere (T2T) level. Comparison of this diploid genome with the CHM13 haploid T2T genome revealed significant variations in the centromere. Outside the centromere, we discovered 11,413 structural variations, including numerous novel ones. We also detected thousands of CN1 alleles that have accumulated high substitution rates and a few that have been under positive selection in the East Asian population. Further, we found that CN1 outperforms CHM13 as a reference genome in mapping and variant calling for the East Asian population owing to the distinct structural variants of the two references. Comparison of SNP calling for a large cohort of 8869 Chinese genomes using CN1 and CHM13 as reference respectively showed that the reference bias profoundly impacts rare SNP calling, with nearly 2 million rare SNPs miss-called with different reference genomes. Finally, applying the CN1 as a reference, we discovered 5.80 Mb and 4.21 Mb putative introgression sequences from Neanderthal and Denisovan, respectively, including many East Asian specific ones undetected using CHM13 as the reference. Our analyses reveal the advances of using CN1 as a reference for population genomic studies and paleo-genomic studies. This complete genome will serve as an alternative reference for future genomic studies on the East Asian population.


Assuntos
Diploide , População do Leste Asiático , Genoma Humano , Telômero , Humanos , Masculino , Povo Asiático/genética , População do Leste Asiático/etnologia , População do Leste Asiático/genética , Genoma Humano/genética , Genômica , Telômero/genética
14.
J Allergy Clin Immunol ; 152(5): 1292-1302, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37422272

RESUMO

BACKGROUND: Phospholipase C (PLC) γ1 is a critical enzyme regulating nuclear factor-κB (NF-κB), extracellular signal-related kinase, mitogen-activated protein kinase, and nuclear factor of activated T cells signaling pathways, yet germline PLCG1 mutation in human disease has not been reported. OBJECTIVE: We aimed to investigate the molecular pathogenesis of a PLCG1 activating variant in a patient with immune dysregulation. METHODS: Whole exome sequencing was used to identify the patient's pathogenic variants. Bulk RNA sequencing, single-cell RNA sequencing, quantitative PCR, cytometry by time of flight, immunoblotting, flow cytometry, luciferase assay, IP-One ELISA, calcium flux assay, and cytokine measurements in patient PBMCs and T cells and COS-7 and Jurkat cell lines were used to define inflammatory signatures and assess the impact of the PLCG1 variant on protein function and immune signaling. RESULTS: We identified a novel and de novo heterozygous PLCG1 variant, p.S1021F, in a patient presenting with early-onset immune dysregulation disease. We demonstrated that the S1021F variant is a gain-of-function variant, leading to increased inositol-1,4,5-trisphosphate production, intracellular Ca2+ release, and increased phosphorylation of extracellular signal-related kinase, p65, and p38. The transcriptome and protein expression at the single-cell level revealed exacerbated inflammatory responses in the patient's T cells and monocytes. The PLCG1 activating variant resulted in enhanced NF-κB and type II interferon pathways in T cells, and hyperactivated NF-κB and type I interferon pathways in monocytes. Treatment with either PLCγ1 inhibitor or Janus kinase inhibitor reversed the upregulated gene expression profile in vitro. CONCLUSIONS: Our study highlights the critical role of PLCγ1 in maintaining immune homeostasis. We illustrate immune dysregulation as a consequence of PLCγ1 activation and provide insight into therapeutic targeting of PLCγ1.


Assuntos
Mutação com Ganho de Função , NF-kappa B , Humanos , NF-kappa B/metabolismo , Transdução de Sinais , Proteínas Quinases Ativadas por Mitógeno/genética , Fosforilação , Fosfolipase C gama/genética
15.
Immunity ; 56(7): 1485-1501.e7, 2023 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-37315560

RESUMO

The interleukin 1 (IL-1) pathway signals through IL-1 receptor type 1 (IL-1R1) and emerges as a central mediator for systemic inflammation. Aberrant IL-1 signaling leads to a range of autoinflammatory diseases. Here, we identified a de novo missense variant in IL-1R1 (p.Lys131Glu) in a patient with chronic recurrent multifocal osteomyelitis (CRMO). Patient PBMCs showed strong inflammatory signatures, particularly in monocytes and neutrophils. The p.Lys131Glu substitution affected a critical positively charged amino acid, which disrupted the binding of the antagonist ligand, IL-1Ra, but not IL-1α or IL-1ß. This resulted in unopposed IL-1 signaling. Mice with a homologous mutation exhibited similar hyperinflammation and greater susceptibility to collagen antibody-induced arthritis, accompanied with pathological osteoclastogenesis. Leveraging the biology of the mutation, we designed an IL-1 therapeutic, which traps IL-1ß and IL-1α, but not IL-1Ra. Collectively, this work provides molecular insights and a potential drug for improved potency and specificity in treating IL-1-driven diseases.


Assuntos
Osteomielite , Receptores de Interleucina-1 , Camundongos , Animais , Receptores de Interleucina-1/genética , Osteomielite/tratamento farmacológico , Osteomielite/genética , Osteomielite/patologia , Inflamação/genética , Inflamação/patologia , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Proteína Antagonista do Receptor de Interleucina 1/genética , Proteína Antagonista do Receptor de Interleucina 1/farmacologia , Transdução de Sinais , Mutação
16.
Front Genet ; 14: 1147819, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37051594

RESUMO

Background: Relationship between periodontitis (PD) and type 1 diabetes (T1D) has been reported, but the detailed pathogenesis requires further elucidation. This study aimed to reveal the genetic linkage between PD and T1D through bioinformatics analysis, thereby providing novel insights into scientific research and clinical treatment of the two diseases. Methods: PD-related datasets (GSE10334, GSE16134, GSE23586) and T1D-related datasets(GSE162689)were downloaded from NCBI Gene Expression Omnibus (GEO). Following batch correction and merging of PD-related datasets as one cohort, differential expression analysis was performed (adjusted p-value <0.05 and ∣log2 fold change| > 0.5), and common differentially expressed genes (DEGs) between PD and T1D were extracted. Functional enrichment analysis was conducted via Metascape website. The protein-protein interaction (PPI) network of common DEGs was generated in The Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database. Hub genes were selected by Cytoscape software and validated by receiver operating characteristic (ROC) curve analysis. Results: 59 common DEGs of PD and T1D were identified. Among these DEGs, 23 genes were commonly upregulated, and 36 genes were commonly downregulated in both PD- and T1D-related cohorts. Functional enrichment analysis indicated that common DEGs were mainly enriched in tube morphogenesis, supramolecular fiber organization, 9 + 0 non-motile cilium, plasma membrane bounded cell projection assembly, glomerulus development, enzyme-linked receptor protein signaling pathway, endochondral bone morphogenesis, positive regulation of kinase activity, cell projection membrane and regulation of lipid metabolic process. After PPI construction and modules selection, 6 hub genes (CD34, EGR1, BBS7, FMOD, IGF2, TXN) were screened out and expected to be critical in linking PD and T1D. ROC analysis showed that the AUC values of hub genes were all greater than 70% in PD-related cohort and greater than 60% in T1D-related datasets. Conclusion: Shared molecular mechanisms between PD and T1D were revealed in this study, and 6 hub genes were identified as potential targets in treating PD and T1D.

17.
J Biophotonics ; 16(5): e202200375, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36740724

RESUMO

In this study, a general and systematical investigation of sub-diffuse reflectance spectroscopy is implemented. A Gegenbauer-kernel phase function-based Monte Carlo is adopted to describe photon transport more efficiently. To improve the computational efficiency and accuracy, two neural network algorithms, namely, back propagation neural network and radial basis function neural network are utilized to predict the absorption coefficient µ a , reduced scattering coefficient µ s ' and sub-diffusive quantifier γ , simultaneously, at multiple source-detector separations (SDS). The predicted results show that the three parameters can be predicated accurately by selecting five SDSs or above. Based on the simulation results, a four wavelength (520, 650, 785 and 830 nm) measurement system using five SDSs is designed by adopting phase-lock-in technique. Furtherly, the trained neural-network models are utilized to extract optical properties from the phantom and in vivo experimental data. The results verify the feasibility and effectiveness of our proposed system and methods in mucosal disease diagnosis.


Assuntos
Algoritmos , Redes Neurais de Computação , Espalhamento de Radiação , Simulação por Computador , Análise Espectral/métodos
18.
IEEE Trans Cybern ; 53(7): 4270-4279, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35417365

RESUMO

In this article, a hybrid visual-ranging servoing method is proposed to realize high-precision positioning tasks with a 6-degree of freedom (DOF) manipulator. This method utilizes the image and measurement features directly in the control loop. Without the need of complex image feature design and attitude estimation, this method realizes the 6-DOF control of a robot. A vital challenge in traditional vision-based systems is avoiding local minima and singularity problems. To tackle this issue, a full-rank interaction matrix hybrid visual servo (FRHVS) design criterion is proposed, which guarantees that the hybrid interaction matrix and its pseudoinverse matrix are both full rank. Moreover, the interaction matrix for these hybrid strategies, which combines image features with other sensors features, is derived in an analytical form. Experiments on a 6-DOF manipulator show that the proposed method is effective and has global asymptotic stability and high precision.

19.
Materials (Basel) ; 15(21)2022 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-36363124

RESUMO

In this work, the effect of secondary-phase precipitation on the microstructure, mechanical properties, and corrosion resistance of 00Cr27Ni7Mo5N hyper-duplex stainless steel (HDSS) during solution treatment was investigated. The results reveal that σ-phase precipitates at the interface between the α and γ phase when the solution treatment temperature is lower than 1070 °C. It is not only brittle, but also prone to create a Cr-depleted zone, which significantly deteriorates the mechanical properties and corrosion resistance. With the increase in the solution treatment temperature, the volume fraction of ferrite gradually increases. The yield strength and tensile strength increase slightly, but the elongation decreases. At the same time, the impact toughness shows a trend of first increasing and then decreasing. When the solution treatment temperature is higher than 1130 °C, Cr2N precipitates in the ferrite. The precipitation of Cr2N causes a decrease in the plastic toughness, but it does not deteriorate the mechanical properties as significantly as the σ phase. However, it can also cause the formation of a Cr-depleted zone that significantly decreases the corrosion resistance. There is no secondary-phase precipitation in the sample after solution treatment at 1100 °C, which shows the best mechanical properties and corrosion resistance.

20.
J Environ Manage ; 324: 116323, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36166869

RESUMO

With the increase of the azo pigment wastewater, it is necessary to seek an efficient and sustainable treatment method to address issues of damaging water ecosystems and human health. In this work, organic representing azo dye Acid Orange 7 (AO7), heavy metal representing hexavalent chromium (Cr(VI)), and inorganic representing ammonia nitrogen (NH4+-N) were selected to roughly simulate the azo pigment wastewater. The simultaneous decontamination of multi-target pollutants by 700 °C pyrolyzed peanut shell biochar (BC) with persulfate (PDS) was evaluated. The results showed that AO7, Cr(VI) and NH4+-N could finally reach 100%, 85% and 30% removal ratios separately in the BC/PDS/mixed pollutants system under certain basic conditions. Functional groups (hydroxyl groups (C-OH) and carboxylic ester/lactone groups (O-C=O)) were found by XPS as competing sites for adsorption and activation and were gradually consumed as the reaction proceeded. Combining a series of experiments results and EPR analysis, it was found that AO7 removal worked best and it relied on both the radical pathway (including SO4•-, •OH, O2-•, but not 1O2) and adsorption. Cr(VI) was mainly adsorbed and reduced by BC surface to form Cr(OH)3 and Cr2O3, and the remaining part could be reduced by O2-•, followed by •OH. NH4+-N was removed primarily by the radical same as AO7. Meanwhile, the three target pollutants have a co-competitive mechanism. Specifically, they competed for radicals and adsorption sites simultaneously, while the presence of AO7 and NH4+-N would consume the generated oxidizing radicals and further promote the removal of Cr(VI). The fixed-bed reactor simulated the continuous treatment of wastewater. Various anions (chloride (Cl-), nitrate (NO3-), carbonate (CO32-), and hydrogen phosphate (HPO42-)) interfered differently with the pollutant removal. These findings demonstrate a new dimension of BC potential for decontamination of azo pigment wastewater.


Assuntos
Águas Residuárias , Poluentes Químicos da Água , Humanos , Ecossistema , Poluentes Químicos da Água/análise , Carvão Vegetal , Cromo , Adsorção , Cloretos
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