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Repair of DNA double strand breaks by homologous recombination (HR) is initiated by Rad51 filament nucleation on single-stranded DNA (ssDNA), which catalyzes strand exchange with homologous duplex DNA. BRCA2 and the Rad51 paralogs are tumor suppressors and critical mediators of Rad51. To gain insight into Rad51 paralog function, we investigated a heterodimeric Rad51 paralog complex, RFS-1/RIP-1, and uncovered the molecular basis by which Rad51 paralogs promote HR. Unlike BRCA2, which nucleates RAD-51-ssDNA filaments, RFS-1/RIP-1 binds and remodels pre-synaptic filaments to a stabilized, "open," and flexible conformation, in which the ssDNA is more accessible to nuclease digestion and RAD-51 dissociation rate is reduced. Walker box mutations in RFS-1, which abolish filament remodeling, fail to stimulate RAD-51 strand exchange activity, demonstrating that remodeling is essential for RFS-1/RIP-1 function. We propose that Rad51 paralogs stimulate HR by remodeling the Rad51 filament, priming it for strand exchange with the template duplex.
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Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/metabolismo , Proteínas Portadoras/metabolismo , ADN de Cadena Simple/metabolismo , Proteínas de Unión al ADN/metabolismo , Recombinación Homóloga , Recombinasa Rad51/metabolismo , Animales , Proteínas de Caenorhabditis elegans/genética , Proteínas de Unión al ADN/genética , Células HEK293 , Humanos , Mutación , Proteínas de Complejo Poro Nuclear/metabolismo , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismoRESUMEN
RNA interference (RNAi) therapeutics are an emerging class of medicines that selectively target mRNA transcripts to silence protein production and combat disease. Despite the recent progress, a generalizable approach for monitoring the efficacy of RNAi therapeutics without invasive biopsy remains a challenge. Here, we describe the development of a self-reporting, theranostic nanoparticle that delivers siRNA to silence a protein that drives cancer progression while also monitoring the functional activity of its downstream targets. Our therapeutic target is the transcription factor SMARCE1, which was previously identified as a key driver of invasion in early-stage breast cancer. Using a doxycycline-inducible shRNA knockdown in OVCAR8 ovarian cancer cells both in vitro and in vivo, we demonstrate that SMARCE1 is a master regulator of genes encoding proinvasive proteases in a model of human ovarian cancer. We additionally map the peptide cleavage profiles of SMARCE1-regulated proteases so as to design a readout for downstream enzymatic activity. To demonstrate the therapeutic and diagnostic potential of our approach, we engineered self-assembled layer-by-layer nanoparticles that can encapsulate nucleic acid cargo and be decorated with peptide substrates that release a urinary reporter upon exposure to SMARCE1-related proteases. In an orthotopic ovarian cancer xenograft model, theranostic nanoparticles were able to knockdown SMARCE1 which was in turn reported through a reduction in protease-activated urinary reporters. These LBL nanoparticles both silence gene products by delivering siRNA and noninvasively report on downstream target activity by delivering synthetic biomarkers to sites of disease, enabling dose-finding studies as well as longitudinal assessments of efficacy.
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Neoplasias Ováricas , Péptidos , Humanos , Femenino , Interferencia de ARN , Péptidos/genética , Neoplasias Ováricas/genética , Neoplasias Ováricas/terapia , Péptido Hidrolasas , ARN Interferente Pequeño/genética , Endopeptidasas , Proteínas Cromosómicas no Histona , Proteínas de Unión al ADNRESUMEN
BACKGROUND: Encouraging antitumor activity of nab-paclitaxel plus S-1 (AS) has been shown in several small-scale studies. This study compared the efficacy and safety of AS versus standard-of-care nab-paclitaxel plus gemcitabine (AG) as a first-line treatment for advanced pancreatic cancer (PC). METHODS: In this multicenter, randomized, phase II trial, eligible patients with unresectable, locally advanced, or metastatic PC were recruited and randomly assigned (1:1) to receive AS (nab-paclitaxel 125 mg/m2 on days 1 and 8; S-1 twice daily on days 1 through 14) or AG (nab-paclitaxel 125 mg/m2 on days 1 and 8; gemcitabine 1000 mg/m2 on days 1 and 8) for 6 cycles. The primary endpoint was progression-free survival (PFS). RESULTS: Between July 16, 2019, and September 9, 2022, 62 patients (AS, nâ =â 32; AG, nâ =â 30) were treated and evaluated. With a median follow-up of 8.36 months at preplanned interim analysis (data cutoff, March 24, 2023), the median PFS (8.48 vs 4.47 months; hazard ratio [HR], 0.402; Pâ =â .002) and overall survival (OS; 13.73 vs 9.59 months; HR, 0.226; Pâ <â .001) in the AS group were significantly longer compared to the AG group. More patients had objective response in the AS group than AG group (37.50% vs 6.67%; Pâ =â .005). The most common grade 3-4 adverse events were neutropenia and leucopenia in both groups, and gamma glutamyl transferase increase was observed only in the AG group. CONCLUSION: The first-line AS regimen significantly extended both PFS and OS of Chinese patients with advanced PC when compared with the AG regimen, with a comparable safety profile. (ClinicalTrials.gov Identifier: NCT03636308).
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Albúminas , Protocolos de Quimioterapia Combinada Antineoplásica , Desoxicitidina , Combinación de Medicamentos , Gemcitabina , Ácido Oxónico , Paclitaxel , Neoplasias Pancreáticas , Tegafur , Humanos , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/mortalidad , Masculino , Desoxicitidina/análogos & derivados , Desoxicitidina/administración & dosificación , Desoxicitidina/uso terapéutico , Desoxicitidina/efectos adversos , Paclitaxel/administración & dosificación , Paclitaxel/uso terapéutico , Paclitaxel/efectos adversos , Paclitaxel/farmacología , Femenino , Tegafur/administración & dosificación , Tegafur/uso terapéutico , Tegafur/efectos adversos , Ácido Oxónico/administración & dosificación , Ácido Oxónico/uso terapéutico , Ácido Oxónico/efectos adversos , Persona de Mediana Edad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Albúminas/administración & dosificación , Albúminas/efectos adversos , Albúminas/uso terapéutico , Anciano , AdultoRESUMEN
Salivary biomarkers can improve the efficacy, efficiency, and timeliness of oral and maxillofacial disease diagnosis and monitoring. Oral and maxillofacial conditions in which salivary biomarkers have been utilized for disease-related outcomes include periodontal diseases, dental caries, oral cancer, temporomandibular joint dysfunction, and salivary gland diseases. However, given the equivocal accuracy of salivary biomarkers during validation, incorporating contemporary analytical techniques for biomarker selection and operationalization from the abundant multi-omics data available may help improve biomarker performance. Artificial intelligence represents one such advanced approach that may optimize the potential of salivary biomarkers to diagnose and manage oral and maxillofacial diseases. Therefore, this review summarized the role and current application of techniques based on artificial intelligence for salivary biomarker discovery and validation in oral and maxillofacial diseases.
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Caries Dental , Enfermedades de la Boca , Enfermedades Periodontales , Humanos , Inteligencia Artificial , Enfermedades de la Boca/diagnóstico , Biomarcadores , Enfermedades Periodontales/diagnósticoRESUMEN
The applications of two-dimensional transition metal carbide/nitride (MXene) in the fields of optoelectronics, sustainable energy, and sensors, among others, have been broadly investigated due to their special electrical, optical, and structural properties. In this Letter, MXene (Ti3C2Tx) has been firstly, to the best of our knowledge, adopted for the application of a photoacoustic transducer by taking advantage of the photothermal property. The efficiency of the photoacoustic transducer based on a sandwich structure of glass/MXene/polydimethylsiloxane (PDMS) has been experimentally demonstrated to be 1.25 × 10-2 by converting laser pulses into ultrasonic waves, generating a high acoustic pressure of 15.7 MPa without additional acoustic focusing. That can be explained by the great light absorption and photothermal conversion of the Ti3C2Tx layer.
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Vitreomacular traction syndrome results from persistent vitreoretinal adhesions in the setting of partial posterior vitreous detachment (PVD). Vitrectomy and reattachment of retina is an effective therapeutic approach. The adhesion between vitreous cortex and internal limiting membrane (ILM) of the retina is stronger in youth, which brings difficulties to induce PVD in vitrectomy. Several clinical investigations demonstrated that intravitreous injection of plasmin before vitrectomy could reduce the risk of detachment. In our study, a novel recombinant human microplasminogen (rhµPlg) was expressed by Pichia pastoris. Molecular docking showed that the binding of rhµPlg with tissue plasminogen activator (t-PA) was similar to plasminogen, suggesting rh µPlg could be activated by t-PA to generate microplasmin (µPlm). Moreover, rhµPlg had higher catalytic activity than plasminogen in amidolytic assays. Complete PVD was found at vitreous posterior pole of 125 µg rhµPlg-treated eyes without morphological change of retina in juvenile rabbits via intraocular injection. Our results demonstrate that rhµPlg has a potential value in the treatment of vitreoretinopathy.
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Enfermedades de la Retina , Desprendimiento del Vítreo , Animales , Humanos , Conejos , Adolescente , Desprendimiento del Vítreo/tratamiento farmacológico , Activador de Tejido Plasminógeno/metabolismo , Activador de Tejido Plasminógeno/farmacología , Cuerpo Vítreo/metabolismo , Simulación del Acoplamiento Molecular , Retina , Vitrectomía/métodos , Plasminógeno/metabolismo , Plasminógeno/farmacología , Inyecciones Intraoculares , Enfermedades de la Retina/metabolismo , Serina ProteasasRESUMEN
Exosomes, small extracellular vesicles that function as a key regulator of cell-to-cell communication, are emerging as a promising candidate for bone regeneration. Here, we aimed to investigate the effect of exosomes from pre-differentiated human alveolar bone-derived bone marrow mesenchymal stromal cells (AB-BMSCs) carrying specific microRNAs on bone regeneration. Exosomes secreted from AB-BMSCs pre-differentiated for 0 and 7 days were cocultured with BMSCs in vitro to investigate their effect on the differentiation of the BMSCs. MiRNAs from AB-BMSCs at different stages of osteogenic differentiation were analyzed. BMSCs seeded on poly-L-lactic acid(PLLA) scaffolds were treated with miRNA antagonist-decorated exosomes to verify their effect on new bone regeneration. Exosomes pre-differentiated for 7 days effectively promoted the differentiation of BMSCs. Bioinformatic analysis revealed that miRNAs within the exosomes were differentially expressed, including the upregulation of osteogenic miRNAs (miR-3182, miR-1468) and downregulation of anti-osteogenic miRNAs (miR-182-5p, miR-335-3p, miR-382-5p), causing activation of the PI3K/Akt signaling pathway. The treatment of BMSC-seeded scaffolds with anti-miR-182-5p decorated exosomes demonstrated enhanced osteogenic differentiation and efficient formation of new bone. In conclusion, Osteogenic exosomes secreted from pre-differentiated AB-BMSCs were identified and the gene modification of exosomes provides great potential as a bone regeneration strategy. DATA AVAILABILITY STATEMENT: Data generated or analyzed in this paper partly are available in the GEO public data repository(http://www.ncbi.nlm.nih.gov/geo).
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Exosomas , Células Madre Mesenquimatosas , MicroARNs , Humanos , Osteogénesis , Exosomas/genética , Exosomas/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Regeneración Ósea/genética , Células Madre Mesenquimatosas/metabolismo , Diferenciación CelularRESUMEN
PURPOSE OR OBJECTIVE: Osteosarcoma is well-known for its high incidence in children and adolescents and long-term bone pain, which seriously reduces the life quality of patients. Cisplatin (CDDP), as the first-line anti-osteosarcoma drug, has been used in many anticancer treatments. At the same time, the serious side effects of platinum (Pt) drugs have also attracted widespread attention. To accurately deliver Pt drugs to the lesion site and realize controlled release of Pt drugs, certain modified delivery systems have been extensively studied. METHODS: Among them, liposomes have been approved for clinical cancer treatment due to their highly biocompatibility and superior modifiability. Here, we developed a bone-targeted dual functional lipid-coated drug delivery system, lipid-coated CDDP alendronate nanoparticles (LCA NPs) to target the bone and precisely deliver the drugs to the tumor site. Cell toxicity, apoptosis and cellular uptake were detected to evaluate the anticancer effect for LCA NPs. Furthermore, transwell assay and wound healing assay were conducted to estimate the osteosarcoma cell migration and invasion. Hemolysis assay was utilized to assess the biocapitibility of the kind of NPs. RESULTS: With the aim of bone-targeted unit alendronate (ALD), LCA NPs serve as a rich bone homing Pt delivery system to exert efficient anticancer effects and synergistically reduce bone resorption and bone loss potentially. CONCLUSIONS: By providing a highly biocompatible platform for osteosarcoma therapy, LCA NPs may help to significantly enhance the anticancer effect of Pt and greatly reduce the systemic toxicity and side effects of Pt towards osteosarcoma.
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Antineoplásicos , Neoplasias Óseas , Nanopartículas , Osteosarcoma , Niño , Humanos , Adolescente , Alendronato , Línea Celular Tumoral , Cisplatino , Osteosarcoma/tratamiento farmacológico , Sistemas de Liberación de Medicamentos , Nanopartículas/uso terapéutico , Neoplasias Óseas/tratamiento farmacológico , LípidosRESUMEN
OBJECTIVES: This study assessed the validity of nomograms for predicting malignant transformation (MT) among patients with oral leukoplakia (OL) and oral lichen planus (OLP). MATERIALS AND METHODS: Two nomograms were identified following a systematic search. Variables to interrogate both nomograms were obtained for a retrospective OL/OLP cohort. Then, the nomograms were applied to estimate MT probabilities twice and their average was used to calculate the discriminatory performance, calibration, and potential net benefit of the models. Subgroup analyses were performed for patients with OL, OLP, and oral epithelial dysplasia. RESULTS: Predicted probabilities were mostly significantly higher among OL/OLP patients who developed MT compared to those who did not (p = <0.001-0.034). AUC values and Brier scores of the nomograms were 0.644-0.844 and 0.040-0.088 among OL patients and 0.580-0.743 and 0.008-0.072 among OLP patients. Decision curve analysis suggested that the nomograms had some net benefit for risk stratification. However, the models did not best binary dysplasia grading in discriminatory validity and net benefit among patients with OL and oral epithelial dysplasia. CONCLUSION: Nomograms for predicting MT may have satisfactory validity among patients with OL than OLP, but they do not outperform binary dysplasia grading in risk stratification of OL.
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OBJECTIVES: Oncologic risk is a serious concern of submental artery island flaps. Here, we introduce the contralateral-based submental artery island flap (C-SAIF) and demonstrate its feasibility and long-term oncological safety in reconstructing oral cancer-related defects. METHODS: An anatomical study was performed concentrating on the pedicle length in seven cadavers. Then, a retrospective study was carried out on C-SAIF patients operated on by a single team. The standard surgical technique of C-SAIF was conducted. Outcomes including operative time, length of hospital stay, volume of intraoperative blood loss, and scores of the Multidisciplinary Salivary Gland Society (MSGS) questionnaire were compared with a similar cohort reconstructed with anterolateral thigh free flap (ALTF). In addition, oncological outcomes were evaluated by the 5-year cumulative survival rate between C-SAIF and ALTF patients. RESULTS: The pedicle length of C-SAIF was sufficient for the flap to be extended to the contralateral oral cavity. Fifty-two patients were included in the retrospective study, and nineteen of them underwent reconstruction with C-SAIF. The operative time of C-SAIF was shorter (p = 0.003), and the intraoperative blood loss was less (p = 0.004) than that of ALTF. There was no difference in MSGS scores. The results of survival analysis revealed comparable survival curves for the two groups in terms of overall survival, disease-specific survival, and disease-free survival. CONCLUSION: C-SAIF is a feasible and reliable flap for reconstructing oral cancer-related defects. Moreover, it is an effective island flap to preserve the perforator and pedicle without compromising oncological safety.
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Colgajos Tisulares Libres , Neoplasias de la Boca , Procedimientos de Cirugía Plástica , Humanos , Estudios Retrospectivos , Pérdida de Sangre Quirúrgica , Estudios de Factibilidad , Neoplasias de la Boca/cirugía , Arterias/cirugíaRESUMEN
OBJECTIVES: The design and fabrication of three-dimensional (3D)-printed patient-specific implants (PSIs) for orthognathic surgery are customarily outsourced to commercial companies. We propose a protocol of designing PSIs and surgical guides by orthognathic surgeons-in-charge instead for wafer-less Le Fort I osteotomy. The aim of this prospective study was to evaluate the accuracy and post-operative complications of PSIs that are designed in-house for Le Fort I osteotomy. MATERIALS AND METHODS: The post-operative cone beam computer tomography (CBCT) model of the maxilla was superimposed to the virtual surgical planning to compare the discrepancies of pre-determined landmarks, lines, and principal axes between the two models. Twenty-five patients (12 males, 13 females) were included. RESULTS: The median linear deviations of the post-operative maxilla of the x, y, and z axes were 0.74 mm, 0.75 mm, and 0.72 mm, respectively. The deviations in the principal axes for pitch, yaw, and roll were 1.40°, 0.90°, and 0.60°, respectively. There were no post-operative complications related to the PSIs in the follow-up period. CONCLUSIONS: The 3D-printed PSIs designed in-house for wafer-less Le Fort I osteotomy are accurate and safe. CLINICAL RELEVANCE: Its clinical outcomes and accuracy are comparable to commercial PSIs for orthognathic surgery. TRIAL REGISTRATION: Clinical trial registration number: HKUCTR-2113. Date of registration: 29 July 2016.
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Implantes Dentales , Procedimientos Quirúrgicos Ortognáticos , Cirujanos , Masculino , Femenino , Humanos , Estudios Prospectivos , Osteotomía Le Fort , Maxilar/diagnóstico por imagen , Maxilar/cirugía , Procedimientos Quirúrgicos Ortognáticos/métodos , Complicaciones Posoperatorias , Imagenología TridimensionalRESUMEN
A pavement's roughness seriously affects its service life and driving comfort. Considering the complexity and low accuracy of the current recognition algorithms for the roughness grade of pavements, this paper proposes a real-time pavement roughness recognition method with a lightweight residual convolutional network and time-series acceleration. Firstly, a random input pavement model is established by the white noise method, and the pavement roughness of a 1/4 vehicle vibration model is simulated to obtain the vehicle vibration response data. Then, the residual convolutional network is used to learn the deep-level information of the sample signal. The residual convolutional neural network recognizes the pavement roughness grade quickly and accurately. The experimental results show that the residual convolutional neural network has a robust feature-capturing ability for vehicle vibration signals, and the classification features can be obtained quickly. The accuracy of pavement roughness classification is as high as 98.7%, which significantly improves the accuracy and reduces the computational effort of the recognition algorithm, and is suitable for pavement roughness grade classification.
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BACKGROUND: Impact and efficiency of oral cancer and oral potentially malignant disorders screening are most realized in "at-risk" individuals. However, tools that can provide essential knowledge on individuals' risks are not applied in risk-based screening. This study aims to optimize a simplified risk scoring system for risk stratification in organized oral cancer and oral potentially malignant disorders screening. METHODS: Participants were invited to attend a community-based oral cancer and oral potentially malignant disorders screening program in Hong Kong. Visual oral examination was performed for all attendees and information on sociodemographic characteristics as well as habitual, lifestyle, familial, and comorbidity risk factors were obtained. Individuals' status of those found to have suspicious lesions following biopsy and histopathology were classified as positive/negative and this outcome was used in a multiple logistic regression analysis with variables collected during screening. Odds ratio weightings were then used to develop a simplified risk scoring system which was validated in an external cohort. RESULTS: Of 979 participants, 4.5% had positive status following confirmatory diagnosis. A 12-variable simplified risk scoring system with weightings was generated with an AUC, sensitivity, and specificity of 0.82, 0.71, and 0.78 for delineating high-risk cases. Further optimization on the validation cohort of 491 participants yielded a sensitivity and specificity of 0.75 and 0.87 respectively. CONCLUSIONS: The simplified risk scoring system was able to stratify oral cancer and oral potentially malignant disorders risk with satisfactory sensitivity and specificity and can be applied in risk-based disease screening.
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Neoplasias de la Boca , Lesiones Precancerosas , Detección Precoz del Cáncer , Humanos , Tamizaje Masivo , Neoplasias de la Boca/diagnóstico , Neoplasias de la Boca/patología , Lesiones Precancerosas/diagnóstico , Lesiones Precancerosas/patología , Medición de RiesgoRESUMEN
OBJECTIVES: This study aimed to establish a neural-related gene risk score (NRGRS) for the prediction of head and neck squamous cell carcinoma prognosis and explore its predictive value on the benefit of immune checkpoint inhibitor therapy. METHODS: Based on the transcriptome data of HNSCC patients (n = 546) from The Cancer Genome Atlas database, 37 neural-related hub genes were identified by weighted gene co-expression network analysis. Four genes (ITGA5, PYGM, GNG7 and ATP2A3) were identified to construct NRGRS using Lasso-Cox regression method based on the derivation cohort and validated in the Gene Expression Omnibus cohort (n = 109). The survival analysis was performed to validate the prognostic value of NRGRS and immune characteristics in NRGRS-defined subgroups were analyzed. RESULTS: NRGRS-high patients had a worse overall survival than NRGRS-low patients. Tumors with high NRGRS were more likely to have high infiltration of naive CD4+ T cells, M0, M2 macrophages and resting mast cells, which illustrated suppressive immunity and less benefit from immunotherapy therapy. CONCLUSION: NRGRS strongly correlates with survival and is a promising biomarker to predict immunotherapy benefits for head and neck cancer patients. This study provides evidence for the potential correlation between neural-related transcriptome alteration and immune activity.
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Mulberry (Morus alba L.) fruit is a fruit with nutritional and medicinal value. It is widely cultivated in different regions of China, which may result in differences in its chemical composition. In this research, 25 mulberry fruit samples from six provinces in China were investigated. The contents of anthocyanins were evaluated by high-performance liquid chromatography (HPLC). The contents of two main anthocyanins, cyanidin-3-O-glucoside (C3G) and cyanidin-3-O-rutinoside (C3R), ranged from 0.656 ± 0.006 mg/g to 4.367 ± 0.243 mg/g and from 0.226 ± 0.007 mg/g to 1.649 ± 0.013 mg/g, respectively. Additionally, the contents of total phenolic, total flavonoid, vitamin C, titratable acids, reducing sugars and antioxidant capacity (FRAP, DPPH, scavenging and hydroxyl radical scavenging activity) were also assessed. The results and principal component analysis showed that the Zhongsang 5801 variety from Sichuan, Dechang had the greatest health value with the highest active compound contents. Based on our analysis, the variety from Sichuan, Dechang is a high-quality plant source for mulberry fruit cultivation. This research provides a basis for the rational development and utilization of mulberry fruit resources in China.
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Antocianinas , Morus , Antocianinas/química , Antioxidantes/química , Frutas/química , Morus/química , Extractos Vegetales/químicaRESUMEN
AIM: A prospective study was conducted to evaluate the accuracy and complications of 3D-printed patient-specific surgical guides and plates that were designed and finished in-house. MATERIALS AND METHODS: Eighteen patients who required advancement genioplasty, with or without concomitant orthognathic surgery, were enrolled in the study. Virtual surgical movements were simulated using the patient's CBCT scans, and the computer-aided designing of patient-specific surgical guides and fixation plates was performed in the authors' department. CBCT scans were taken at 1-month postoperatively, and stereolithographic models of the preoperative virtual plan and the postoperative CBCT scan were registered. Part comparisons were performed to assess the accuracy of the movements. The median, minimum, and maximum differences were measured. Two landmarks, the Menton (Me) and Pogonion (Pog), were also used to compare the differences locally. RESULTS: The median deviation for the 18 cases was 0.19 mm. The median deviation at the Me and Pog were 0.67 and 0.41 mm, respectively. There was no significant correlation between the surgical movement of < 7 mm advancement and the transfer accuracy (P = 0.77). No adverse events or complications were reported within the postoperative 6-month period. CONCLUSION: The protocol of self-designed 3D-printed patient-specific surgical guides and plates provided an accurate method to transfer the virtual surgical plan to the operating theater. (Int J Comput Dent 2022;25(4):369-0; doi: 10.3290/j.ijcd.b2599791).
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Procedimientos Quirúrgicos Ortognáticos , Cirugía Asistida por Computador , Humanos , Mentoplastia/métodos , Estudios Prospectivos , Cirugía Asistida por Computador/métodos , Procedimientos Quirúrgicos Ortognáticos/métodos , Impresión Tridimensional , Diseño Asistido por Computadora , Imagenología Tridimensional/métodosRESUMEN
BACKGROUND: Surgeons are pursuing accurate head and neck reconstruction to enhance aesthetic and functional outcomes after oncologic resection. This study aimed to investigate whether accuracy of head and neck reconstruction is improved with the use of three-dimensionally (3D)-printed patient-specific surgical plates compared with conventional plates. METHODS: In this comparative study, patients were prospectively recruited into the study group (3DJP16) with 3D-printed patient-specific surgical plates. The patients in control group with conventional surgical plates were from a historic cohort in the same unit. The primary end point of the study was the accuracy of head and neck reconstruction. The secondary end points were accuracy of osteotomy, intraoperative blood loss, total operative time, and length of hospital stay. RESULTS: The study recruited of 33 patients, including 17 in the study group and 16 in the control group. The patients' baseline characteristics were similar between the two groups. The absolute distance deviation of the maxilla or mandible was 1.5 ± 0.5 mm in the study group and 2.1 ± 0.7 mm in the control group [mean difference, - 0.7 mm; 95% confidence interval (CI) - 1.1 to - 0.3; p = 0.003], showing superior accuracy of reconstruction for the patients with 3D-printed patient-specific surgical plates. Improved accuracy of reconstruction also was detected in terms of bilateral mandibular angles and bone grafts. Concerning the secondary end points, the accuracy of the osteotomy was similar in the two groups. No difference was found regarding intraoperative blood loss, total operative time, or length of hospital stay. CONCLUSIONS: This is the first study to prove that compared with conventional plates, 3D-printed patient-specific surgical plates improve the accuracy of oncologic head and neck reconstruction.
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Reconstrucción Mandibular , Procedimientos de Cirugía Plástica , Cirugía Asistida por Computador , Placas Óseas , Humanos , Mandíbula/cirugía , Impresión TridimensionalRESUMEN
The rapid increase in both the quantity and complexity of data that are being generated daily in the field of environmental science and engineering (ESE) demands accompanied advancement in data analytics. Advanced data analysis approaches, such as machine learning (ML), have become indispensable tools for revealing hidden patterns or deducing correlations for which conventional analytical methods face limitations or challenges. However, ML concepts and practices have not been widely utilized by researchers in ESE. This feature explores the potential of ML to revolutionize data analysis and modeling in the ESE field, and covers the essential knowledge needed for such applications. First, we use five examples to illustrate how ML addresses complex ESE problems. We then summarize four major types of applications of ML in ESE: making predictions; extracting feature importance; detecting anomalies; and discovering new materials or chemicals. Next, we introduce the essential knowledge required and current shortcomings in ML applications in ESE, with a focus on three important but often overlooked components when applying ML: correct model development, proper model interpretation, and sound applicability analysis. Finally, we discuss challenges and future opportunities in the application of ML tools in ESE to highlight the potential of ML in this field.
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Ciencia Ambiental , Aprendizaje AutomáticoRESUMEN
The CARMA1/Bcl10/MALT1 (CBM) signalosome mediates antigen receptor-induced NF-κB signaling to regulate multiple lymphocyte functions. While CARMA1 and Bcl10 contain caspase recruitment domains (CARDs), MALT1 is a paracaspase with structural similarity to caspases. Here we show that the reconstituted CBM signalosome is a helical filamentous assembly in which substoichiometric CARMA1 nucleates Bcl10 filaments. Bcl10 filament formation is a highly cooperative process whose threshold is sensitized by oligomerized CARMA1 upon receptor activation. In cells, both cotransfected CARMA1/Bcl10 complex and the endogenous CBM signalosome are filamentous morphologically. Combining crystallography, nuclear magnetic resonance, and electron microscopy, we reveal the structure of the Bcl10 CARD filament and the mode of interaction between CARMA1 and Bcl10. Structure-guided mutagenesis confirmed the observed interfaces in Bcl10 filament assembly and MALT1 activation in vitro and NF-κB activation in cells. These data support a paradigm of nucleation-induced signal transduction with threshold response due to cooperativity and signal amplification by polymerization.
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Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras de Señalización CARD/genética , Caspasas/genética , Guanilato Ciclasa/genética , Proteínas de Neoplasias/genética , Transducción de Señal/genética , Proteínas Adaptadoras Transductoras de Señales/química , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteína 10 de la LLC-Linfoma de Células B , Sitios de Unión , Proteínas Adaptadoras de Señalización CARD/química , Proteínas Adaptadoras de Señalización CARD/metabolismo , Caspasas/química , Caspasas/metabolismo , Cristalografía por Rayos X , Regulación de la Expresión Génica , Guanilato Ciclasa/química , Guanilato Ciclasa/metabolismo , Humanos , Células Jurkat , Proteína 1 de la Translocación del Linfoma del Tejido Linfático Asociado a Mucosas , Complejos Multiproteicos/química , Complejos Multiproteicos/genética , FN-kappa B/química , FN-kappa B/genética , Proteínas de Neoplasias/química , Proteínas de Neoplasias/metabolismo , Unión Proteica , Estructura Secundaria de ProteínaRESUMEN
Titanium dioxide (TiO2) is a well-known photocatalyst in the applications of water contaminant treatment. Traditionally, the kinetics of photo-degradation rates are obtained from experiments, which consumes enormous labor and experimental investments. Here, a generalized predictive model was developed for prediction of the photo-degradation rate constants of organic contaminants in the presence of TiO2 nanoparticles and ultraviolet irradiation in aqueous solution. This model combines an artificial neural network (ANN) with a variety of factors that affect the photo-degradation performance, i.e., ultraviolet intensity, TiO2 dosage, organic contaminant type and initial concentration in water, and initial pH of the solution. The molecular fingerprints (MF) were used to interpret the organic contaminants as binary vectors, a format that is machine-readable in computational linguistics. A dataset of 446 data points for training and testing was collected from the literature. This predictive model shows a good accuracy with a root mean square error (RMSE) of 0.173.