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BACKGROUND: CDK4 is highly expressed and associated with poor prognosis and decreased survival in advanced neuroblastoma (NB). Targeting CDK4 degradation presents a potentially promising therapeutic strategy compared to conventional CDK4 inhibitors. However, the autophagic degradation of the CDK4 protein and its anti-proliferation effect in NB cells has not been mentioned. RESULTS: We identified autophagy as a new pathway for the degradation of CDK4. Firstly, autophagic degradation of CDK4 is critical for NVP-BEZ235-induced G0/G1 arrest, as demonstrated by the overexpression of CDK4, autophagy inhibition, and blockade of autophagy-related genes. Secondly, we present the first evidence that p62 binds to CDK4 and then enters the autophagy-lysosome to degrade CDK4 in a CTSB-dependent manner in NVP-BEZ235 treated NB cells. Similar results regarding the interaction between p62 and CDK4 were observed in the NVP-BEZ235 treated NB xenograft mouse model. CONCLUSIONS: Autophagic degradation of CDK4 plays a pivotal role in G0/G1 cell cycle arrest in NB cells treated with NVP-BEZ235.
Subject(s)
Autophagy , Cyclin-Dependent Kinase 4 , G1 Phase Cell Cycle Checkpoints , Neuroblastoma , Cyclin-Dependent Kinase 4/metabolism , Neuroblastoma/metabolism , Neuroblastoma/pathology , Neuroblastoma/drug therapy , Neuroblastoma/genetics , Humans , Animals , Mice , Autophagy/drug effects , G1 Phase Cell Cycle Checkpoints/drug effects , Cell Line, Tumor , Xenograft Model Antitumor Assays , Quinolines/pharmacology , Resting Phase, Cell Cycle/drug effects , Cell Proliferation/drug effects , Imidazoles/pharmacology , Mice, Nude , ProteolysisABSTRACT
Background/purpose: Periodontitis is associated with various systemic diseases, potentially facilitated by the passage of Porphyromonas gingivalis outer membrane vesicles (Pg-OMVs). Several recent studies have suggested a connection between Pg-OMVs and neuroinflammation and neurodegeneration, but the precise causal relationship remains unclear. This study aimed to investigate the mechanisms underlying these associations using in vitro models. Materials and methods: Isolated Pg-OMVs were characterized by morphology, size, and gingipain activity. We exposed SH-SY5Y neuroblastoma cells and BV-2 microglial cells to various concentrations of Pg-OMVs. Cell morphology, a 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, an enzyme-linked immunosorbent assay, and Western blot analysis were used to evaluate the cellular mechanism underlying Pg-OMV-induced neurotoxicity in neuronal cells and inflammatory responses in microglial cells. Results: Exposure to Pg-OMVs induced neurotoxicity in SH-SY5Y cells, as evidenced by cellular shrinkage, reduced viability, activation of apoptotic pathways, and diminished neuronal differentiation markers. Gingipain inhibition mitigated these effects, suggesting that gingipain mediates Pg-OMVs-induced neurotoxicity in SH-SY5Y cells. Our research on neuroinflammation suggests that upon endocytosis of Pg-OMVs by BV-2 cells, lipopolysaccharide (LPS) can modulate the production of inducible nitric oxide synthase and tumor necrosis factor-alpha by activating pathways that involve phosphorylated AKT and the phosphorylated JNK pathway. Conclusion: Our study demonstrated that following the endocytosis of Pg-OMVs, gingipain can induce neurotoxicity in SH-SY5Y cells. Furthermore, the Pg-OMVs-associated LPS can trigger neuroinflammation via AKT and JNK signaling pathways in BV-2 cells.
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Objective:To establish a staging system for guiding clinical treatment and prognostic risk assessment by retrospectively analyzing the cases with radionecrosis of the nasopharynx and skull base ï¼RNSBï¼ after radiotherapy for nasopharyngeal carcinoma. Methods:A total of 86 cases of RNSB from January 2019 to December 2022 visited Department of Otorhinolaryngology Head and Neck, the People's Hospital of Guangxi Zhuang Autonomous Region. Seventeen patients gave up the treatment, and 69 patients who underwent treatment were included for analysis. By analyzing the results of electronic nasopharyngolaryngoscopy combined with magnetic resonance ï¼MRï¼, CT, and other imaging examinations, a staging system for RNSB was proposed. The relationship between the staging system and the surgical effectiveness and clinical prognosis was further analyzed. Results:According to the severity and extent of destruction of soft tissue, bone, and the adjacent neurovascular structures, the RNSB was categorized into closed type ï¼n=5ï¼ and open type ï¼n=64ï¼, of which the open type was subdivided into five types: type â ï¼n=4ï¼, type â ¡ï¼n=6ï¼, type â ¢ï¼n=39, of which 21 cases were type â ¢a and 18 cases were type â ¢bï¼, type â £ï¼n=12ï¼, and type â ¤ï¼n=8ï¼. The clinical stage of RNSB were classified based on nasopharyngolaryngoscopy and imaging examinations, receiving the second course of radiotherapy or not, the involvement of the infection site, the extent of bone destruction, the degree of internal carotid artery involvement, and the degree of brain tissue necrosis: stageâ ï¼1-2 scoresï¼, 11 cases at stageâ ¡ï¼3-4 scoresï¼, 24 cases at stage â ¢ï¼5-6 scoresï¼, and 30 cases at stage â £ï¼ ≥ 7 scores or moreï¼. Twenty-two patients chose conservative treatment ï¼2 patients at stage â , 3 patients at stage â ¡, 7 patients at stage â ¢, and 10 patients at stage â £ï¼. Forty-seven patients chose nasal endoscopic surgical treatment ï¼2 patients at stage â , 8 patients at stage â ¡, 17 patients at stage â ¢, and 20 patients at stage â £ï¼, of which 16 cases had received free mucosal flap and/or stented septum mucosal flap repair. Patients at stages â , â ¡, and â ¢ achieved satisfactory efficacy after surgical treatment. In addition, higher clinical stage was found to correlate with the worse prognosis and higher incidence of perioperative complications, which included failure of healing because of surgical site infection, cerebrospinal fluid nasal leakage, progressive osteonecrosis, nasopharyngeal hemorrhage, and death. Conclusion:The staging system proposed in our study can be used for early detection of RNSB during regular follow-up, and is also valuable for clinical treatment guidance and prognosis assessment.
Subject(s)
Nasopharyngeal Neoplasms , Nasopharynx , Necrosis , Radiation Injuries , Skull Base , Humans , Male , Female , Skull Base/diagnostic imaging , Nasopharyngeal Neoplasms/radiotherapy , Retrospective Studies , Middle Aged , Radiation Injuries/etiology , Adult , Aged , Magnetic Resonance Imaging , Prognosis , Tomography, X-Ray ComputedABSTRACT
High channel current of the high electron mobility transistors (HEMTs) and high relative responsivity of the photodetectors (PDs) were demonstrated in the AlGaN/AlN/GaN channel-stacking epitaxial structures. The interference properties of the X-ray curves indicated high-quality interfaces of the conductive channels. The AlGaN/AlN/GaN interfaces were observed clearly in the transmission electron microscope micrograph. The saturation I ds currents of the HEMT structures were increased by adding a number of channels. The conductive properties of the channel-stacking structures corresponded to the peaks of the transconductance (g m) spectra in the HEMT structures. The depletion-mode one- and two-channel HEMT structures can be operated at the cutoff region by increasing the reverse V gs bias voltages. Higher I ds current in the active state and lower current in the cutoff state were observed in the two-channel HEMT structure compared with one- and three-channel HEMT structures. For the channel-stacking metal-semiconductor-metal photodetector structures, the peak responsivity was observed at almost 300 nm incident monochromic light, which was increased by adding a number of channel layers. The channel current of the HEMT devices and the photocurrent in the PD devices were increased by adding a number of two-dimensional electron gas (2DEG) channels. By using a flat gate metal layer, the two-channel AlGaN/AlN/GaN HEMT structures exhibited a high I ds current, a low cutoff current, and a high peak g m value and have the potential for GaN-based power devices, fast portable chargers, and ultraviolet PD applications.
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The typical lake wetlands in the middle and lower reaches of the Yangtze River are important wintering sites of cranes in China. The spatiotemporal evolution of crane populations and their habitats has great value in clarifying the pivotal role of regional lake wetlands in biodiversity conservation. Therefore, 2562 data points of four crane species were selected in this study. The data reflected the distributional position of the cranes over the period 2000-2020. Twelve surrounding environmental factors were selected to investigate the spatiotemporal evolution in the study area by using the MaxEnt model. The Jackknife method was used to identify the main environmental factors affecting the choice of crane habitats. The results indicated that: (1) Developed land in the study area increased by 42,795.81 hm2. The crane populations were mainly distributed in the farmland and mudflat, and their number decreased yearly. (2) From 2000 to 2020, the area of suitable crane habitat experienced an overall decrease. Specifically, the mid-suitable area dwindled by 6234.23 hm2, marking a substantial reduction of 52.05 %. Similarly, the most suitable area saw a decline of 786.41 hm2, representing a noteworthy decrease of 71.09 %. (3) The findings from the analysis of influencing factors revealed a dynamic pattern over the years. Habitat type, water density, and distance to water were the main influencing factors in the study area from 2000 to 2020. This study provides a new perspective on the conservation and structural habitat restoration of crane populations in the middle and lower reaches of the Yangtze River.
Subject(s)
Lakes , Wetlands , Animals , Ecosystem , Biodiversity , Birds , China , WaterABSTRACT
Non-destructive processing of powders into macroscopic materials with a wealth of structural and functional possibilities has immeasurable scientific significance and application value, yet remains a challenge using conventional processing techniques. Here we developed a universal fibration method, using two-dimensional cellulose as a mediator, to process diverse powdered materials into micro-/nanofibres, which provides structural support to the particles and preserves their own specialties and architectures. It is found that the self-shrinking force drives the two-dimensional cellulose and supported particles to pucker and roll into fibres, a gentle process that prevents agglomeration and structural damage of the powder particles. We demonstrate over 120 fibre samples involving various powder guests, including elements, compounds, organics and hybrids in different morphologies, densities and particle sizes. Customized fibres with an adjustable diameter and guest content can be easily constructed into high-performance macromaterials with various geometries, creating a library of building blocks for different fields of applications. Our fibration strategy provides a universal, powerful and non-destructive pathway bridging primary particles and macroapplications.
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Using sulfate radicals to initiate polymer production in persulfate-based advanced oxidation processes (AOPs) is an emerging strategy for organics removal. However, our understanding of this process remains limited due to a dearth of efficient methods for in situ and real time monitoring of polymerization kinetics. This study leverages plasmonic colorimetry to monitor the polymerization kinetics of an array of aromatic pollutants in the presence of sulfate radicals. We observed that the formation of polymer shells on the surfaces of gold nanoparticles (AuNPs) led to an increase and red shift in their localized surface plasmon resonance (LSPR) band as a result of an increased refractive index surrounding the AuNP surfaces. This observation aligns with Mie theory simulations and transmission electron microscopy-electron energy loss spectroscopy characterizations. Our study demonstrated that the polymerization kinetics exhibits a significant reliance on the electrophilicity and quantity of benzene rings, the concentration of aromatic pollutants, and the dosage of oxidants. In addition, we found that changes in LSPR band wavelength fit well into a pseudo-first-order kinetic model, providing a comprehensive and quantitative insight into the polymerization kinetics involving diverse organic compounds. This technique holds the potential for optimizing AOP-based water treatment by facilitating the polymerization of aromatic pollutants.
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OBJECTIVES: To investigate if spatial recurrence pattern is associated with patient prognosis, and whether MRI vascular habitats can predict spatial pattern. METHODS: In this retrospective study, 69 patients with locally recurrent high-grade gliomas (HGGs) were included. The cohort was divided into intra-resection cavity recurrence (ICR) and extra-resection cavity recurrence (ECR) patterns, according to the distance between the location of the recurrent tumor and the resection cavity or surgical region. Four vascular habitats, high angiogenic tumor, low angiogenic tumor, infiltrated peripheral edema, and vasogenic peripheral edema, were segmented and vascular heterogeneity parameters were analyzed. The survival and diagnostic performance under different spatial recurrence patterns were analyzed by Kaplan-Meier and ROC. A nomogram model was constructed by regression analysis and validated by bootstrapping technique. RESULTS: Progression-free survival (PFS) and overall survival (OS) were longer for ICR (n = 32) than those for ECR (n = 37) (median PFS: 8 vs. 5 months, median OS: 17 vs. 13 months, p < 0.05). MRI vascular habitat analyses showed ECR had higher median relative cerebral blood volume (rCBVmedian) at each habitat than ICR (all p < 0.01). The rCBVmedian at IPE had good diagnostic performance (AUC: 0.727, 95%CI: 0.607, 0.828). The AUC of the nomogram based on MRI vascular habitats and clinical factors was 0.834 (95%CI: 0.726, 0.913) and was confirmed as 0.833 (95%CI: 0.830, 0.836) by bootstrapping validation. CONCLUSIONS: The spatial pattern of locally recurrent HGGs is associated with prognosis. MRI vascular heterogeneity parameter could be used as a non-invasive imaging marker to predict spatial recurrence pattern. CLINICAL RELEVANCE STATEMENT: Vascular heterogeneity parameters based on MRI vascular habitat analyses can non-invasively predict the spatial patterns of locally recurrent high-grade gliomas, providing a new diagnostic basis for clinicians to develop the extent of surgical resection and postoperative radiotherapy planning. KEY POINTS: ⢠Intra-resection cavity pattern was associated with longer progression-free survival and overall survival in locally recurrent high-grade gliomas. ⢠Higher vascular heterogeneities in extra-resection cavity recurrence than in intra-resection cavity recurrence and the vascular heterogeneity parameters had good diagnostic performance in discriminating spatial recurrence pattern. ⢠A nomogram model based on MRI vascular habitats and clinical factors had good performance in predicting spatial recurrence pattern.
Subject(s)
Brain Neoplasms , Glioma , Humans , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/surgery , Retrospective Studies , Glioma/diagnostic imaging , Glioma/surgery , Magnetic Resonance Imaging/methods , EdemaABSTRACT
OBJECTIVE: To investigate the effect of intramedullary nail fixation (IMN) and minimally invasive percutaneous plate internal fixation (MIPPO) techniques on tibiofibular fractures and their effect on platelet activation and serum transforming growth factor-ß1 (TGF-ß1) and bone morphogenetic protein-2 (BMP-2). METHODS: Total of 105 patients with tibiofibular fractures from February 2019 to February 2020 were selected and divided into 53 cases in the MIPPO group and 52 cases in the IMN group. There were 29 males and 24 females with an average age of (41.74±6.05) years old in MIPPO group;in IMN group, 31 males and 21 females with an average age of (40.59±5.26) years old. The perioperative surgical indexes, postoperative complications, ankle function recovery at 12 months postoperatively, platelet activation indexes at 3 and 7 days preoperatively and postoperatively, and serum TGF-ß1 and BMP-2 levels at 4 and 8 weeks preoperatively and postoperatively were compared between the two groups. RESULTS: The operating time and fracture healing time in the MIPPO group were shorter than those in the IMN group(P<0.05); Compared with the preoperative period, the levels of GMP-140, PAC-1, CD63, and CD61 increased in both groups at 3 and 7 days after surgery, but were lower in the MIPPO group than in the IMN group(P<0.05);the levels of serum TGF-ß1 and BMP-2 increased in both groups at 4 and 8 weeks after surgery compared with the preoperative period, and the postoperative complication rate in the MIPPO group was lower than that in the IMN group(P<0.05);the difference was not statistically significant in the excellent rate of ankle function recovery at 12 months follow-up after surgery between two groups(P>0.05). CONCLUSION: Both intramedullary nail fixation and MIPO technique for treatment of tibia and fibula fractures can improve ankle joint function, but the latter has the advantages of short operation time, fast fracture healing, fewer complications, and light platelet activation. Serum TGF-ß1, BMP-2 level improves quickly.
Subject(s)
Fracture Fixation, Intramedullary , Fractures, Multiple , Tibial Fractures , Male , Female , Humans , Adult , Middle Aged , Tibia/surgery , Tibia/injuries , Transforming Growth Factor beta1 , Fracture Fixation, Intramedullary/methods , Tibial Fractures/surgery , Fracture Fixation, Internal/methods , Bone Plates , Fracture Healing , Postoperative Complications , Treatment Outcome , Bone Morphogenetic Proteins , Minimally Invasive Surgical Procedures/methods , Retrospective StudiesABSTRACT
The photothermal effect in nanomaterials, resulting from resonant optical absorption, finds wide applications in biomedicine, cancer therapy, and microscopy. Despite its prevalence, the photothermal effect in light-absorbing nanoparticles has typically been assessed using bulk measurements, neglecting near-field effects. Beyond standard imaging and therapeutic uses, nanosecond-transient photothermal effects have been harnessed for bacterial inactivation, neural stimulation, drug delivery, and chemical synthesis. While scanning probe microscopy and electron microscopy offer single-particle imaging of photothermal fields, their slow speed limits observations to milliseconds or seconds, preventing nanoscale dynamic investigations. Here, we introduce decoupled optical force nanoscopy (Dofn), enabling nanometer-scale mapping of photothermal forces by exploiting unique phase responses to temporal modulation. We employ the photothermal effect's back-action to distinguish various time frames within a modulation period. This allows us to capture the dynamic photothermal process of a single gold nanorod in the nanosecond range, providing insights into non-stationary thermal diffusion at the nanoscale.
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INTRODUCTION: CCN1 is an immediate-early gene product pivotal for arthritis progression. We have previously shown that sirtuin 6 (SIRT6) inhibited hypoxia-induced CCN1 expression in osteoblasts. Herein we examined the contribution of cyclic AMP-responsive element binding protein (CREB)/CRE to this suppressive action and the influence of CCN1 on cyclooxygenase (COX) 2 synthesis. MATERIALS AND METHODS: MC3T3-E1 murine osteoblasts were cultured under normoxia (21% oxygen) or hypoxia (2% oxygen). Expressions of CCN1, phospho-CREB (Ser133), COX2 and relevant kinases were assessed by Western blot. SIRT6 was overexpressed in cultured osteoblasts and arthritic joints by a lentiviral-based technique. Activities of CCN1 gene promoter constructs were examined by luciferase reporter assay. Interaction between CREB and CCN1 promoter was assessed by chromatin immunoprecipitation (ChIP). Collagen-induced arthritis (CIA) was established in 20 rats to evaluate the effects of SIRT6 therapy on osteoblastic expressions of phospho-CREB, CCN1 and COX2. RESULTS: SIRT6 suppressed hypoxia-enhanced CCN1 expression and CREB phosphorylation. Attenuation of calcium/calmodulin-dependent protein kinase II (CaMKII) may be responsible for SIRT6-induced CREB inhibition. CRE at - 286 bp upstream of the ATG start codon was essential for CCN1 expression under hypoxia and SIRT6 reduced hypoxia-stimulated CREB/CRE interaction. Forced expression of CREB rescued SIRT6-suppressed CCN1 synthesis. CCN1 induced COX2 expression in osteoblasts. In rat CIA, the therapeutic effect of SIRT6 was accompanied by decreases in osteoblastic expressions of phospho-CREB, CCN1 and COX2. CONCLUSION: Our study indicated that the benefits of SIRT6 to inflammatory arthritis and bone resorption are at least partially derived from its modulation of CREB/CCN1/COX2 pathway in osteoblasts.
Subject(s)
Arthritis, Experimental , Sirtuins , Rats , Mice , Animals , Cyclooxygenase 2/genetics , Cyclooxygenase 2/metabolism , Cyclooxygenase 2/pharmacology , Osteoblasts/metabolism , Cyclic AMP Response Element-Binding Protein/metabolism , Cyclic AMP Response Element-Binding Protein/pharmacology , Hypoxia , Arthritis, Experimental/genetics , Arthritis, Experimental/metabolism , Phosphorylation , Oxygen/metabolism , Oxygen/pharmacology , Sirtuins/metabolism , Sirtuins/pharmacology , Cyclic AMP/metabolism , Cyclic AMP/pharmacologyABSTRACT
INTRODUCTION: We have previously demonstrated that auxiliary metformin therapy promotes healing of apical periodontitis. Here we aimed to investigate the effects of metformin on osteoblast differentiation and osteoclast formation in cultured cells and rat apical periodontitis. METHODS: Murine pre-osteoblasts MC3T3-E1 and macrophages RAW264.7 were cultured under hypoxia (2% oxygen) or normoxia (21% oxygen) and stimulated with receptor activator of nuclear factor-κB ligand (RANKL) when indicated. Metformin was added to the cultures to evaluate its anti-hypoxic effects. Expressions of osteoblast differentiation regulator runt-related transcription factor 2 (RUNX2), RANKL, and osteoclast marker tartrate-resistant acid phosphatase (TRAP) were assessed by Western blot. Apical periodontitis was induced in mandibular first molars of 10 Sprague-Dawley rats. Root canal therapy with or without metformin supplement was performed. Periapical bone resorption was measured by micro-computed tomography. Immunohistochemistry was used to examine RUNX2, RANKL, and TRAP expressions. RESULTS: Hypoxia suppressed RUNX2 expression and enhanced RANKL synthesis in pre-osteoblasts. TRAP production increased in macrophages after hypoxia and/or RANKL stimulation. Metformin reversed hypoxia-induced RUNX2 suppression and RANKL synthesis in pre-osteoblasts. Metformin also inhibited hypoxia and RANKL-enhanced TRAP synthesis in macrophages. Intracanal metformin diminished bone loss in rat apical periodontitis. Comparing with vehicle control, cells lining bone surfaces in metformin-treated lesions had significantly stronger expression of RUNX2 and decreased synthesis of RANKL and TRAP. CONCLUSIONS: Alleviation of bone resorption by intracanal metformin was associated with enhanced osteoblast differentiation and diminished osteoclast formation in rat apical periodontitis. Our results endorsed the role of metformin as an effective medicament for inflammatory bone diseases.
Subject(s)
Bone Resorption , Metformin , Periapical Periodontitis , Rats , Mice , Animals , Osteoclasts , Core Binding Factor Alpha 1 Subunit/metabolism , Metformin/pharmacology , Metformin/therapeutic use , X-Ray Microtomography , Rats, Sprague-Dawley , Bone Resorption/metabolism , Osteoblasts , Periapical Periodontitis/pathology , Cell Differentiation , Hypoxia/metabolism , Oxygen/metabolism , RANK Ligand/metabolismABSTRACT
A wood cell wall with cellulose as the key scaffold is a natural hierarchical lamellar structure. This wood-derived cellulose scaffold has recently attracted enormous attention and interest, but almost all efforts have been devoted to its whole tissue functionalization. Here, we report the short ultrasonic processing of a wood cellulose scaffold to directly generate 2D cellulose materials. The obtained 2D cellulose nanosheets consist of many highly oriented fibrils densely arranged and can be further converted to ultrathin 2D carbon nanosheets. The nanoparticles, nickel-iron layer double hydroxide nanoflowers, manganese dioxide nanorods, and zinc oxide nanostars, are successfully loaded in the 2D nanosheet, providing a versatile 2D platform strategy for excellent 2D hybrid nanomaterials.
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Objective:To evaluate the diagnostic accuracy of the convolutional neural networkï¼CNNï¼ in diagnosing nasopharyngeal carcinoma using endoscopic narrowband imaging. Methods:A total of 834 cases with nasopharyngeal lesions were collected from the People's Hospital of Guangxi Zhuang Autonomous Region between 2014 and 2016. We trained the DenseNet201 model to classify the endoscopic images, evaluated its performance using the test dataset, and compared the results with those of two independent endoscopic experts. Results:The area under the ROC curve of the CNN in diagnosing nasopharyngeal carcinoma was 0.98. The sensitivity and specificity of the CNN were 91.90% and 94.69%, respectively. The sensitivity of the two expert-based assessment was 92.08% and 91.06%, respectively, and the specificity was 95.58% and 92.79%, respectively. There was no significant difference between the diagnostic accuracy of CNN and the expert-based assessment ï¼P=0.282, P=0.085ï¼. Moreover, there was no significant difference in the accuracy in discriminating early-stage and late-stage nasopharyngeal carcinomaï¼P=0.382ï¼. The CNN model could rapidly distinguish nasopharyngeal carcinoma from benign lesions, with an image recognition time of 0.1 s/piece. Conclusion:The CNN model can quickly distinguish nasopharyngeal carcinoma from benign nasopharyngeal lesions, which can aid endoscopists in diagnosing nasopharyngeal lesions and reduce the rate of nasopharyngeal biopsy.
Subject(s)
Narrow Band Imaging , Nasopharyngeal Neoplasms , Humans , Nasopharyngeal Carcinoma , China , Neural Networks, Computer , Nasopharyngeal Neoplasms/diagnostic imagingABSTRACT
Human pluripotent stem cells provide an inexhaustible model to study human embryogenesis in vitro. Recent studies have provided diverse models to generate human blastoids by self-organization of different pluripotent stem cells or somatic reprogramming intermediates. However, whether blastoids can be generated from other cell types or whether they can recapitulate postimplantation development in vitro is unknown. Here, we develop a strategy to generate human blastoids from heterogeneous intermediates with epiblast, trophectoderm, and primitive endoderm signatures of the primed-to-naïve conversion process, which resemble natural blastocysts in morphological architecture, composition of cell lineages, transcriptome, and lineage differentiation potential. In addition, these blastoids reflect many features of human peri-implantation and pregastrulation development when further cultured in an in vitro 3D culture system. In summary, our study provides an alternative strategy to generate human blastoids and offers insights into human early embryogenesis by modeling peri- and postimplantation development in vitro.
Subject(s)
Pluripotent Stem Cells , Humans , Pluripotent Stem Cells/metabolism , Embryo, Mammalian/metabolism , Cell Differentiation , Blastocyst , Cell Lineage , Embryonic DevelopmentABSTRACT
Airborne particulate matter (PM) pollution has caused a public health threat, including nanoscale particles, especially with emerging infectious diseases and indoor and vehicular environmental pollution. However, most existing indoor air filtration units are expensive, energy-intensive, and bulky, and there is an unavoidable trade-off between low-efficiency PM0.3/pathogen interception, PM removal, and air resistance. Herein, we designed and synthesized a two-dimensional continuous cellulose-sheath/net with a unique dual-network corrugated architecture to manufacture high-efficiency air filters and even N95 particulate face mask. Combined with its sheath/net structured pores (size 100-200 nm) consisting of a cellulose framework (1-100 nm diameter), the cellulose sheath/net filter offers high-efficiency air filtration (>99.5338%, Extrafine particles; >99.9999%, PM2.5), low-pressure drops, and a robustness quality factor of >0.14 Pa-1, utilizing their ultralight weight of 30 mg/m2 and physical adhesion and sieving behaviors. Simultaneously, masks prepared with cellulose-sheath/net filters are more likely to capture and block smaller particles than the N95 standard. The synthesis of such materials with their nanoscale features and designed macrostructures may suggest new design criteria for a novel generation of high-efficiency air filter media for different applications such as personal protection products and industrial dust removal.
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Developing affordable and effective carbon dioxide (CO2) capture technology has attracted substantial intense attention due to the continued growth of global CO2 emissions. The low-cost and biodegradable cellulosic materials are developed into CO2 adsorbent recently. Epoxy-functionalized polyethyleneimine modified epichlorohydrin-cross-linked cellulose aerogel (EBPCa) was synthesized from alkaline cellulose solution, epoxy-functionalized polyethyleneimine (EB-PEI), and epichlorohydrin (ECH) through the freezing-thawing processes and freeze-drying. The Fourier transform infrared spectroscopy confirmed that the cellulose aerogel was successfully modified by EB-PEI. The X-ray photoelectron spectroscopy analyses confirmed the presence of N 1s and Cl 2p in EBPCa, meaning that the chlorine of ECH and the amino groups of EB-PEI exist in the cellulose surface. The obtained sample has a rich porous structure with a specific surface area in the range of 97.5-149.5 m2/g. Owing to its uniformly three-dimensional porous structure, the sample present preferable rigidity and carrying capacity, which 1 g of sample could easily carry the weight of a 3000 ml Erlenmeyer flask filled with water (total 4 kg). The sample showed good adsorption performance, with a maximum adsorption capacity of 6.45 mmol/g. This adsorbent has broad prospects in the CO2 capture process.
Subject(s)
Carbon Dioxide , Cellulose , Cellulose/chemistry , Carbon Dioxide/chemistry , Polyethyleneimine/chemistry , Epichlorohydrin , Spectroscopy, Fourier Transform Infrared , Adsorption , ChloridesABSTRACT
Pressure injuries are a common problem resulting in poor prognosis, long-term hospitalization, and increased medical costs in an aging society. This study developed a method to do automatic segmentation and area measurement of pressure injuries using deep learning models and a light detection and ranging (LiDAR) camera. We selected the finest photos of patients with pressure injuries, 528 in total, at National Taiwan University Hospital from 2016 to 2020. The margins of the pressure injuries were labeled by three board-certified plastic surgeons. The labeled photos were trained by Mask R-CNN and U-Net for segmentation. After the segmentation model was constructed, we made an automatic wound area measurement via a LiDAR camera. We conducted a prospective clinical study to test the accuracy of this system. For automatic wound segmentation, the performance of the U-Net (Dice coefficient (DC): 0.8448) was better than Mask R-CNN (DC: 0.5006) in the external validation. In the prospective clinical study, we incorporated the U-Net in our automatic wound area measurement system and got 26.2% mean relative error compared with the traditional manual method. Our segmentation model, U-Net, and area measurement system achieved acceptable accuracy, making them applicable in clinical circumstances.
Subject(s)
Deep Learning , Humans , Image Processing, Computer-Assisted/methods , Prospective Studies , Taiwan , Pressure UlcerABSTRACT
OBJECTIVES: First, we retrospectively compared the clinical efficacy of concurrent chemoradiotherapy combined with nimotuzumab vs. chemoradiotherapy alone in patients with nasopharyngeal carcinoma (NPC) and cervical lymph node metastasis. Second, we analyzed the value of Ki-67 as a predictor of nimotuzumab efficacy. METHODS: From January 2012 to December 2019, 1250 patients with cervical lymph node metastasis eligible for enrollment were included, of whom 383 were treated with concurrent chemoradiotherapy combined with nimotuzumab (targeted therapy group), and 867 were treated with concurrent chemoradiotherapy (CRT group). A total of 381 pairs of patients were matched using 1:1 propensity score matching, and differences in clinical prognosis were compared between the two groups. RESULTS: Overall survival (OS) (P = 0.028), disease-free survival (DFS) (P = 0.040), and distant metastasis-free survival (DMFS) (P = 0.040) were better in the targeted therapy compared to the CRT group. Multivariate analysis revealed that clinical staging, chemotherapy, and nimotuzumab therapy were predictors of OS and DFS. In the targeted therapy group, patients with ≥ 50% Ki-67 positivity had better OS and DFS rates than those with < 50% Ki-67 positivity. CONCLUSIONS: In patients with stage N1-3 NPC and lymph node metastasis, the addition of nimotuzumab to concurrent chemoradiotherapy may provide additional survival benefits. Ki-67 is a potential biomarker with clinical predictive value for the efficacy of nimotuzumab combined with chemoradiotherapy.
Subject(s)
Nasopharyngeal Neoplasms , Humans , Nasopharyngeal Carcinoma/pathology , Nasopharyngeal Neoplasms/pathology , Lymphatic Metastasis , Retrospective Studies , Ki-67 Antigen , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chemoradiotherapy , Neoplasm StagingABSTRACT
Understanding the mechanism of photoacoustic generation at the nanoscale is key to developing more efficient photoacoustic devices and agents. Unlike the far-field photoacoustic effect that has been well employed in imaging, the near-field profile leads to a complex wave-tissue interaction but is understudied. Here we show that the spatiotemporal profile of the near-field photoacoustic waves can be shaped by laser pulses, anisotropy, and the spatial arrangement of nanostructure(s). Using a gold nanorod as an example, we discovered that the near-field photoacoustic amplitude in the short axis is â¼75 % stronger than the long axis, and the anisotropic spatial distribution converges to an isotropic spherical wave at â¼50 nm away from the nanorod's surface. We further extend the model to asymmetric gold nanostructures by arranging isotropic nanoparticles anisotropically with broken symmetry to achieve a precisely controlled near-field photoacoustic "focus" largely within an acoustic wavelength.