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Objectives: Locally advanced bulky unresectable head neck cancer causes significant tumor mass effects, leading to severe symptoms. This study aims to report the safety and outcomes in patients undergoing Lattice spatially fractionated radiotherapy (Lattice SFRT) for locally advanced bulky unresectable head and neck cancer. Methods: Patients with bulky head and neck cancer received Lattice SFRT between June 2022 and June 2023. Lattice SFRT was administered in 2-3 fractions of 12 Gy (Gy) using 6-megavolt (MV) photon beams through a multileaf collimator (MLC) based on VMAT technology. The primary endpoints were symptomatic and tumor response rates. Secondary endpoints were overall survival, local control, and acute and late toxicity rates. Results: 19 consecutive patients meeting the study criteria were identified, predominantly with squamous cell carcinoma histology. The median patient age was 62 years (range 39-79 years), and the median tumor volume was 208 cc (cc) (range 48-701 cc). All patients completed radiotherapy. Among all investigated patients, 16 of 19 (84.2 %) patients achieved an objective response, including 10 individuals achieved a partial response (PR), with 3 of them exhibiting regression exceeding 75 %. 17 patients showed symptom improvement to varying degrees. Acute toxicity of Radiation Therapy Oncology Group (RTOG) grade 1 or higher occurred in 5 patients, while no grade 3 adverse events was observed. Conclusions: Lattice SFRT proves to be a viable treatment option for the palliative management of bulky head and neck cancer. In the palliative setting, Lattice SFRT offers timely symptom relief, enhancing patient quality of life. Treatment toxicity remains within an acceptable range. Continued optimization of Lattice SFRT delivery and patient selection can benefit from further data on the feasibility and efficacy of this radiation modality.
ABSTRACT
Pseudorabies virus is a swine alpha-herpesvirus. We demonstrated that alpha-herpesvirus infection downregulates HSF1, a master transcription factor in the heat shock response. The serine/threonine protein kinase activity of late viral protein UL13 is indispensable for HSF1 depletion and phosphorylation, and UL13 does not degrade HSF1 posttranslationally but inhibits the HSF1 mRNA level. Importantly, UL13 increased HSF1 activity even though it reduced HSF1 mRNA. Furthermore, viral replication markedly decreased in the HSF1 knockout cell line or in the presence of an HSF1-specific inhibitor. Interestingly, HSF1 knockout accelerated the activation of NF-κB and p38MAPK. The K96 loci of UL13 are important to induce high levels of IL-6, TNF-α, and IL-ß cytokines while playing a crucial role in promoting mild interstitial pneumonia, liver necrosis, and severe inflammatory cell infiltration in the footpad. Thus, UL13 steers the heat shock response to promote viral replication and the inflammatory response. IMPORTANCE: PRV is a ubiquitous pathogen that infects a variety of mammals, such as pigs, ruminants, carnivores, and rodents as well as human beings, causing enormous economic losses in the swine industry. Here, we employed PRV as a model to determine the relationship between α-herpesvirus and the inflammatory response. Overall, our findings indicated that PRV infection inhibits the level of HSF1 mRNA via the serine/threonine protein kinase activity of UL13. Additionally, we discovered that HSF1 was involved in NF-κB activation upon PRV infection. PRV UL13 orchestrates the level of HSF1 mRNA, HSF1 protein phosphorylation, and priming of the inflammatory response. Our study reveals a novel mechanism employed by UL13 serine/threonine protein kinase activity to promote the inflammatory response, providing novel clues for therapy against alpha-herpesvirus infection.
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Human epidermal growth factor receptor 2 (HER2) is a transmembrane receptor-like protein with tyrosine kinase activity that plays a vital role in processes such as cell proliferation, differentiation, and angiogenesis. The degree of malignancy of different cancers, notably breast cancer, is strongly associated with HER2 amplification, overexpression, and mutation. Currently, widely used clinical HER2 tyrosine kinase inhibitors (TKIs), such as lapatinib and neratinib, have several drawbacks, including susceptibility to drug resistance caused by HER2 mutations and adverse effects from insufficient HER2 selectivity. To address these issues, it is essential to create innovative HER2 TKIs with enhanced safety, effectiveness against mutations, and high selectivity. Typically, SPH5030 has advanced to phase I clinical trials for its strong suppression of four HER2 mutations. This review discusses the latest research progress in HER2 TKIs, with a focus on the structural optimization process and structure-activity relationship analysis. In particular, this study highlights promising design strategies to address these challenges, providing insightful information and inspiration for future development in this field.
Subject(s)
Antineoplastic Agents , Drug Design , Protein Kinase Inhibitors , Receptor, ErbB-2 , Humans , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/chemistry , Receptor, ErbB-2/antagonists & inhibitors , Receptor, ErbB-2/metabolism , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Structure-Activity Relationship , Molecular Structure , Neoplasms/drug therapyABSTRACT
BACKGROUND: The incidence of breast cancer ranks highest among cancers and is exceedingly heterogeneous. Immunohistochemical staining is commonly used clinically to identify the molecular subtype for subsequent treatment and prognosis. PURPOSE: Raman spectroscopy and support vector machine (SVM) learning algorithm were utilized to identify blood samples from breast cancer patients in order to investigate a novel molecular typing approach. METHOD: Tumor tissue coarse needle aspiration biopsy samples, and peripheral venous blood samples were gathered from 459 invasive breast cancer patients admitted to the breast department of Sichuan Cancer Hospital between June 2021 and September 2022. Immunohistochemical staining and in situ hybridization were performed on the coarse needle aspiration biopsy tissues to obtain their molecular typing pathological labels, including: 70 cases of Luminal A, 167 cases of Luminal B (HER2-positive), 57 cases of Luminal B (HER2-negative), 84 cases of HER2-positive, and 81 cases of triple-negative. Blood samples were processed to obtained Raman spectra taken for SVM classification models establishment with machine algorithms (using 80% of the sample data as the training set), and then the performance of the SVM classification models was evaluated by the independent validation set (20% of the sample data). RESULTS: The AUC values of SVM classification models remained above 0.85, demonstrating outstanding model performance and excellent subtype discrimination of breast cancer molecular subtypes. CONCLUSION: Raman spectroscopy of serum samples can promptly and precisely detect the molecular subtype of invasive breast cancer, which has the potential for clinical value.
Subject(s)
Breast Neoplasms , Receptor, ErbB-2 , Spectrum Analysis, Raman , Support Vector Machine , Humans , Female , Breast Neoplasms/blood , Breast Neoplasms/pathology , Breast Neoplasms/genetics , Spectrum Analysis, Raman/methods , Middle Aged , Receptor, ErbB-2/metabolism , Receptor, ErbB-2/analysis , Receptor, ErbB-2/blood , Adult , Biomarkers, Tumor/blood , Molecular Typing/methods , Aged , Prognosis , Neoplasm InvasivenessABSTRACT
Given the significant therapeutic efficacy of anti-HER-2 treatment, the HER-2 status is a crucial piece of information that must be obtained in breast cancer patients. Currently, as per guidelines, HER-2 status is typically acquired from breast tissue of patients. However, there is growing interest in obtaining HER-2 status from serum and other samples due to the convenience and potential for dynamic monitoring. In this study, we have developed a serum Raman spectroscopy technique that allows for the rapid acquisition of HER-2 status in a convenient manner. The established HER-2 negative and positive classification model achieved an area under the curve of 0.8334. To further validate the reliability of our method, we replicated the process using immunohistochemistry and in situ hybridization. The results demonstrate that serum Raman spectroscopy, coupled with artificial intelligence algorithms, is an effective technical approach for obtaining HER-2 status.
Subject(s)
Breast Neoplasms , Humans , Female , Breast Neoplasms/drug therapy , Artificial Intelligence , Reproducibility of Results , Spectrum Analysis, Raman , Receptor, ErbB-2/genetics , Receptor, ErbB-2/therapeutic use , In Situ HybridizationABSTRACT
Introduction: This study aimed to evaluate the feasibility of using general Raman spectroscopy as a method to screen for breast cancer. The objective was to develop a machine learning model that utilizes Raman spectroscopy to detect serum samples from breast cancer patients, benign cases, and healthy subjects, with puncture biopsy as the gold standard for comparison. The goal was to explore the value of Raman spectroscopy in the differential diagnosis of breast cancer, benign lesions, and healthy individuals. Methods: In this study, blood serum samples were collected from a total of 333 participants. Among them, there were 129 cases of tumors (pathologically diagnosed as breast cancer and labeled as cancer), 91 cases of benign lesions (pathologically diagnosed as benign and labeled as benign), and 113 cases of healthy controls (labeled as normal). Raman spectra of the serum samples from each group were collected. To classify the normal, benign, and cancer sample groups, principal component analysis (PCA) combined with support vector machine (SVM) was used. The SVM model was evaluated using a cross-validation method. Results: The results of the study revealed significant differences in the mean Raman spectra of the serum samples between the normal and tumor/benign groups. Although the mean Raman spectra showed slight variations between the cancer and benign groups, the SVM model achieved a remarkable prediction accuracy of up to 98% for classifying cancer, benign, and normal groups. Discussion: In conclusion, this exploratory study has demonstrated the tremendous potential of general Raman spectroscopy as a clinical adjunctive diagnostic and rapid screening tool for breast cancer.
ABSTRACT
Pseudorabies virus (PRV) belongs to the alpha herpesvirus family and is responsible for Aujeszky's disease in pigs. Similar to other alpha herpesviruses, PRV establishes a lifelong latent infection in trigeminal ganglion. These latently infected pigs serve as a reservoir for recurrent infections when reactivation is triggered, making the eradication of PRV a challenging task. However, the molecular mechanism underlying PRV latency and reactivation in neurons is still poorly understood due to limitations in the in vitro model. To establish a pseudorabies virus latency and reactivation model in primary neuron cultures, we isolated dorsal root ganglion (DRG) from newborn Kunming mice using a method named epineurium-pulling for DRG collection (EPDC) and cultured primary neurons in vitro. A dual-colour recombinant PRV BAC mRuby-VP16 was constructed and 0.5 multiplicity of infection (MOI) was found as an appropriate dose in the presence of aciclovir to establish latency. Reactivation was induced using UV-inactivated herpesviruses or a series of chemical inhibitors. Interestingly, we found that not only UV-PRV, but also UV-HSV-1 and UV-BHoV-5 were able to induce rapid PRV reactivation. The efficiency of reactivation for LY294002, forskolin, etoposide, dexamethasone, and acetylcholine was found to be dependent on their concentration. In conclusion, we developed a valuable model of PRV latency and reactivation, which provides a basis for future mechanism research.
Subject(s)
Herpesvirus 1, Suid , Pseudorabies , Mice , Animals , Swine , Herpesvirus 1, Suid/physiology , Ganglia, Spinal , Virus Latency , Virus ActivationABSTRACT
Supersaturating drug delivery system (SDDS) is a promising approach to enhance the solubility of hydrophobic functional components. However, SDDS is thermodynamically unstable and crystallization tends to occur. In this work, curcumin was used as a model compound, and the crystallization inhibitory effect of konjac glucomannan (KGM), sodium alginate (SA) and xanthan gum (XTG) on curcumin in supersaturated solution was investigated. Amorphous solubility of curcumin was determined using ultraviolet extinction, fluorescence spectroscopy and dynamic light scattering methods. Nucleation induction time (NIT) and crystal growth rate of curcumin were evaluated using ultraviolet probe in the absence and presence of various natural polysaccharides (NPs). Results showed that amorphous solubility of curcumin was approximately 30 µg/mL in pH 6.8 phosphate buffer. NPs used in this work restrained nucleation or crystal growth of curcumin effectively. The NITs of curcumin in the absence of NPs and in the presence of XTG, KGM and SA (1 µg/mL) were 3.7, 60.7, 20.0 and 8.0 min, respectively. The crystal growth rate of curcumin in the absence of NPs and in the presence of XTG, SA and KGM (1 µg/mL) were 0.0103, 0.00752, 0.00286 and 0.000306 min-1, respectively. The nucleation inhibitory effect of NPs on curcumin was ranked as XTG > KGM > SA. The order of crystal growth inhibition capacity of NPs was KGM > SA > XTG. In conclusion, NPs could be incorporated into SDDS to maintain supersaturation of hydrophobic components for enhanced bioavailability.
Subject(s)
Curcumin , Crystallization , Curcumin/pharmacology , Alginates , Mannans/chemistry , SolubilityABSTRACT
It has been proved that Raman spectral intensities could be used to diagnose lung cancer patients. However, the application of Raman spectroscopy in identifying the patients with pulmonary nodules was barely studied. In this study, we revealed that Raman spectra of serum samples from healthy participants and patients with benign and malignant pulmonary nodules were significantly different. A support vector machine (SVM) model was developed for the classification of Raman spectra with wave points, according to ANOVA test results. It got a good performance with a median area under the curve (AUC) of 0.89, when the SVM model was applied in discriminating benign from malignant individuals. Compared with three common clinical models, the SVM model showed a better discriminative ability and added more net benefits to participants, which were also excellent in the small-size nodules. Thus, the Raman spectroscopy could be a less-invasive and low-costly liquid biopsy.
ABSTRACT
Leucine-rich repeat containing 15 (LRRC15) has been identified as a contributing factor for cartilage damage in osteoarthritis; however, its involvement in rheumatoid arthritis (RA) and the underlying mechanisms have not been well characterized. The purpose of this study was to explore the function of LRRC15 in RA-associated fibroblast-like synoviocytes (RA-FLS) and in mice with collagen-induced arthritis (CIA) and to dissect the epigenetic mechanisms involved. LRRC15 was overexpressed in the synovial tissues of patients with RA, and LRRC15 overexpression was associated with increased proliferative, migratory, invasive, and angiogenic capacities of RA-FLS and accelerated release of pro-inflammatory cytokines. LRRC15 knockdown significantly inhibited synovial proliferation and reduced bone invasion and destruction in CIA mice. Runt-related transcription factor 1 (RUNX1) transcriptionally represses LRRC15 by binding to core-binding factor subunit beta (CBF-ß). Overexpression of RUNX1 significantly inhibited the invasive phenotype of RA-FLS and suppressed the expression of proinflammatory cytokines. Conversely, the effects of RUNX1 were significantly reversed after overexpression of LRRC15 or inhibition of RUNX1-CBF-ß interactions. Therefore, we demonstrated that RUNX1-mediated transcriptional repression of LRRC15 inhibited the development of RA, which may have therapeutic effects for RA patients.
Subject(s)
Arthritis, Experimental , Arthritis, Rheumatoid , Animals , Mice , Arthritis, Experimental/metabolism , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/metabolism , Cell Movement , Cell Proliferation , Cells, Cultured , Core Binding Factor Alpha 2 Subunit/pharmacology , Cytokines/metabolism , Epigenesis, Genetic , Fibroblasts/metabolism , Synovial Membrane/metabolism , HumansABSTRACT
Amorphous solid dispersion (ASD) is a promising strategy to enhance solubility and bioavailability of poorly water-soluble drugs. Due to higher free energy of ASD, supersaturated drug solution could be generated during dissolution. When amorphous solubility of a drug is exceeded, drug-rich nanodroplets could form and act as a reservoir to maintain the maximum free drug concentration in solution, facilitating the absorption of the drug in vivo. Dissolution behavior of ASD has received increasing interests. This review will focus on the recent advances in ASD dissolution, including the generation and maintenance of supersaturated drug solution in absence or presence of liquid-liquid phase separation. Mechanism of drug release from ASD including polymer-controlled dissolution and drug-controlled dissolution will be introduced. Formation of amorphous drug-rich nanodroplets during dissolution and the underlying mechanism will be discussed. Phase separation morphology of hydrated ASD plays a critical role in dissolution behavior of ASD, which will be highlighted. Supersaturated drug solution shows poor physical stability and tends to crystallize. The effect of polymer and surfactant on supersaturated drug solution will be demonstrated and some unexpected results will be shown. Physicochemical properties of drug and polymer could impact ASD dissolution and some of them even show opposite effect on dissolution and physical stability of ASD in solid state, respectively. This review will contribute to a better understanding of ASD dissolution and facilitate a rational design of ASD formulation.
Subject(s)
Polymers , Surface-Active Agents , Solubility , Drug Liberation , Polymers/chemistryABSTRACT
Whether long non-coding RNA Mir-99a-Let-7c Cluster Host Gene (LncRNA MIR99AHG) is involved in osteoporosis (OP) remains vague, so we hereby center on its implication. Old C57BL/6J mice were injected with the silencing lentivirus of MIR99AHG and subjected to microCT analysis and immunohistochemistry on osteogenic cells. The osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) with or without transfection was determined by alkaline phosphatase (ALP) and Alizarin Red S staining. Total N(6)-methyladenosine (m6A) on the bone marrow mesenchymal stem cells (BMSCs) was quantified. The potential methylation site and the complementary binding sites with candidate microRNA (miR) were predicted via bioinformatic analyses, with the latter being confirmed via dual-luciferase reporter, RNA immunoprecipitation and RNA pull-down assays. Quantitative real-time PCR and Western blot were used for quantification assays. MIR99AHG was decreased during the osteogenic differentiation of BMSCs, where increased Osterix (OSX), Collagen, Type I, Alpha 1 (Col1A1), Osteocalcin (OCN) and RUNX Family Transcription Factor 2 (RUNX2) as well as more color-stained areas were found. Also, silencing MIR99AHG relieved the OP in mice and reduced the loss of osteogenic cells. M6A methylation in undifferentiated BMSCs was low and MIR99AHG overexpression abolished the effects of overexpressed METTL3 on promoting osteogenic differentiation. MiR-4660, which was downregulated in BMSCs without differentiation but increased during osteogenic differentiation, could bind with MIR99AHG. Furthermore, miR-4660 promoted osteogenic differentiation and reversed the effects of overexpressed MIR99AHG. The present study demonstrated that METTL3-mediated LncRNA MIR99AHG methylation enhanced the osteogenic differentiation of BMSCs via targeting miR-4660.
Subject(s)
Mesenchymal Stem Cells , MicroRNAs , RNA, Long Noncoding , Mice , Animals , RNA, Long Noncoding/genetics , Osteogenesis/genetics , Methylation , Cells, Cultured , Mice, Inbred C57BL , Cell Differentiation/genetics , MicroRNAs/genetics , Mesenchymal Stem Cells/metabolism , Bone Marrow Cells/metabolism , Methyltransferases/metabolismABSTRACT
PURPOSE: To reduce the potential risk during radiotherapy treatment of patients with head and neck tumors, we improved upon the design of an existing immobilization device by adding a feature to improve patient safety during emergency releases, and we verified its clinical application. METHOD: We designed an improved automatic unlocking baseplate (AUB), and conducted a dosimetry comparison with Solo Align Full Body System (SAFBS, Klarity, China). The dosimetry comparison included dose-attenuation measurements and results from human simulation. We selected four points for measurement to allow comparison between the SAFBS and our AUB. A simulated human body model was used for CT scanning, whereby the target area and structure and simulated radiotherapy plan were conducted according to the American Academy of Pain Medicine Task Group-119 report (TG-119), whereby the dose differences were compared. The purpose of the clinical test was to verify the reliability of the AUB system in practical clinical applications. The application tests were conducted in CT simulation (CT-sim) and treatment rooms. The test included assessments of the stability of the system and the reliability of our device. RESULTS: The dose-attenuation measurements of the two baseplates were as follows: The transmission values with our unlocking system were 0.10% higher at the first point and 0.67% lower at the third. The same dose was obtained at points 2 and 4. In the simulation study, the PTV of the AUB was lower than that of the SAFBS, including 0.39% lower D99 and 0.18% lower D90 . Among the organ-at-risk doses, the average dose of the AUB in the spinal cord was 0.6% higher than that of the SAFBS, and the average dose in the left and right parotid glands was more than 1.4% lower than that of SAFBS. The clinical test results were applied in treatment room and a CT-sim room, which show a 100% success rate after being unlocked more than 5000 times. CONCLUSION: The AUB designed for head and neck patients had good functional versatility, the dose distribution met the requirements, and the automatic unlocking function was demonstrated to be stable and reliable.
Subject(s)
Radiotherapy, Conformal , Radiotherapy, Intensity-Modulated , Humans , Radiotherapy Planning, Computer-Assisted/methods , Radiotherapy Dosage , Reproducibility of Results , Radiotherapy, Intensity-Modulated/methods , Radiotherapy, Conformal/methodsABSTRACT
STUDY DESIGN: A cross-sectional study. OBJECTIVE: To quantify the severity of neurogenic intermittent claudication (NIC) for patients with lumbar spinal stenosis (LSS) based on the center of pressure trajectory. SUMMARY OF BACKGROUND DATA: NIC is one of the typical symptoms of LSS. So far, the severity level of NIC is mainly evaluated by the subjective description of patients, which might be biased by patients' background differences and thus lead to an ineffective diagnosis or inappropriate treatment for LSS. Therefore, it remains necessary to develop a reliable clinical technique for quantitative evaluation of NIC to achieve more effective therapy for LSS. MATERIALS AND METHODS: In the present study, the Footscan pressure system was used to detect the center of pressure trajectory. The real-time walking distance (rtWD) and the corresponding displacement of the medial-lateral center of pressure (ML-COP) were calculated based on the trajectory. The differences of ML-COP between LSS and control groups were analyzed using a one-way repeated measures analysis of variance. Regression and Pearson correlation analysis were used to investigate the correlation between rtWD and ML-COP, as well as the relation between the Oxford Claudication Score (OCS) and clinical evaluation indicators. RESULTS: The present study included 31 LSS patients and 31 healthy controls. There were no significant differences in demographic data between the two groups ( P >0.05). The results indicated that ML-COP would increase with the number of laps in the LSS group while not in the control group. Also, a linear relationship was identified between the ML-COP and rtWD for LSS patients ( R2 >0.80, P <0.05). Since the incremental rate of ML-COP for LSS patients was reflected by the regression coefficients of the linear regression analysis, thus the regression coefficients were defined as the claudication correlation coefficients (CCCs). In addition, it was indicated by the statistical analysis that there was a strong positive correlation between OCS and CCC ( r =0.96; P <0.001) and a medium negative correlation with final walking distance ( r =-0.67; P <0.001). It was also noticed that there was no significant correlation between the average ML-COP and OCS ( r =-0.03; P =0.864). CONCLUSIONS: The ML-COP of LSS patients would increase with the patients' walking distance. This incremental rate, characterized by the CCC, would be used as an effective indicator to quantify the severity level of the NIC for potentially more accurate and reliable diagnosis, evaluation, and treatment of LSS. LEVEL OF EVIDENCE: 3.
Subject(s)
Spinal Stenosis , Humans , Spinal Stenosis/complications , Spinal Stenosis/diagnosis , Spinal Stenosis/therapy , Intermittent Claudication/diagnosis , Cross-Sectional Studies , Gait , Leg , Lumbar VertebraeABSTRACT
BACKGROUND: This study aimed to compare the clinical and radiographic outcomes of the proximal femoral nail antirotation (PFNA) and external fixation in the management of unstable intertrochanteric fractures in elderly patients. METHODS: Eighty-seven of 114 patients with unstable intertrochanteric fractures were included in this study between January 2015 and June 2019, 46 were fixed with PFNA implant and 41 with external fixator. Patient baseline characteristics, functional and radiographic results, and postoperative complication were documented and compared between the 2 groups. RESULTS: Prolonged operation duration, increased fluoroscopy time, and excess blood loss occurred in PFNA group. The functional results scores seemed higher in the PFNA than external fixation group in the first semester, and thereafter, there was no significant difference between groups. On early postoperative radiographs, better femur neck-shaft angle was acquired in the external fixators device, but the difference did not continue at final visit. The incidence rate of overall complications was 43.5% for the group PFNA and 100% for the group external fixation. CONCLUSIONS: Fewer postoperative complications occurred in PFNA than external fixator group when unstable intertrochanteric fractures were treated. Nevertheless, there was no significant difference detected in final functional and radiographic outcome between the 2 groups.
Subject(s)
Femoral Fractures , Fracture Fixation, Intramedullary , Hip Fractures , Aged , Bone Nails , External Fixators , Femoral Fractures/surgery , Fracture Fixation , Fracture Fixation, Intramedullary/methods , Hip Fractures/surgery , Humans , Postoperative Complications/epidemiology , Retrospective Studies , Treatment OutcomeABSTRACT
Based on the modified Hopkinson torsion bar, a high-temperature dynamic shear test method was proposed for the Ti-1023 alloy, and the microstructural evolution of the tested material at different temperatures was studied. By using the modified high-temperature Hopkinson torsion bar, high-temperature testing within 1000 °C can be achieved. As the specimen-heating rate was fast, and the temperature gradient of the experimental environment was small, valid experimental data can be ensured during the experiment. The experimental results show that stress-induced martensite can significantly enhance the strength of the Ti-1023 alloy. Dynamically recrystallized grains similar to those in adiabatic shear bands appear in the microstructure of the Ti-1023 alloy after severe plastic deformation. Therefore, it is possible to regulate the content of stress-induced martensite in the microstructure to improve the mechanical properties of other alloys that are similar to ß titanium alloys.
ABSTRACT
In this work, a core-satellite optoplasmonic particle containing a silica microsphere covered with gold nanoparticles (AuNPs) was developed through wet chemistry synthesis in aqueous phase. The electroless deposition and galvanic replacement were employed to anchor AuNPs onto silica sphere surface. The escalated as well as expanded electric field enhancement within the dielectric-metallic interface was analyzed through finite difference time domain (FDTD) simulation. The numerical models and the surface-enhancement Raman spectroscopy (SERS) measurements over blood serum both support that the equatorial plane is the preferred collecting plane for improved signal intensity and stability. The nanocomposite emerged lower relative standard deviation (RSD) in repetitive measurement compared to AuNPs. In practice, this hybrid structure was applied for lung cancer diagnosis based on serum SERS spectra analysis of the patients diagnosed with nodules. The prediction with the aid of principal component analysis (PCA) and support-vector machine (SVM) was attempted for the classification of healthy, benign and relatively malignant sample groups. The accuracy of distinguish benign samples from malignant ones reaches over 90%. These advantages make the structure a promising SERS substrate for the early screening of cancer based on the non-invasive biological samples.
Subject(s)
Lung Neoplasms , Metal Nanoparticles , Early Detection of Cancer , Gold/chemistry , Humans , Lung Neoplasms/diagnosis , Metal Nanoparticles/chemistry , Silicon Dioxide/chemistry , Spectrum Analysis, Raman/methodsABSTRACT
The development of thermostable vaccines can relieve the bottleneck of existing vaccines caused by thermal instability and subsequent poor efficacy, which is one of the predominant reasons for the millions of deaths caused by vaccine-preventable diseases. Research into the mechanism of viral thermostability may provide strategies for developing thermostable vaccines. Using Newcastle disease virus (NDV) as model, we identified the negative surface charge of attachment glycoprotein as a novel determinant of viral thermostability. It prevented the temperature-induced aggregation of glycoprotein and subsequent detachment from virion surface. Then structural stability of virion surface was improved and virus could bind to and infect cells efficiently after heat-treatment. Employing the approach of surface charge engineering, thermal stability of NDV and influenza A virus (IAV) vaccines was successfully improved. The increase in the level of vaccine thermal stability was determined by the value-added in the negative surface charge of the attachment glycoprotein. The engineered live and inactivated vaccines could be used efficiently after storage at 37°C for at least 10 and 60 days, respectively. Thus, our results revealed a novel surface-charge-mediated link between HN protein and NDV thermostability, which could be used to design thermal stable NDV and IAV vaccines rationally.
Subject(s)
Newcastle Disease , Viral Vaccines , Animals , Chickens/metabolism , Glycoproteins , HN Protein/metabolism , Newcastle Disease/prevention & control , Newcastle disease virus/metabolismABSTRACT
The printing quality and strength of specialty papers such as money, maps, newspapers and bank notes have been a significance challenge in recent years. The adhesive effect between ink and paper is depend on both the secondary binding force between the molecules and the mechanical anchoring effect of the ink on the paper. Also, the porous and fibrous structures of base paper restrain its application in printed products because of the strong capillary effect leading to the diffusion of ink particles. To address the problems involved in ink diffusion and mechanical reinforcement, surface sizing is an attractive choice from the perspective of paper handling. Herein, the surface sizing system of specialty paper with an interpenetrating polyvinyl alcohol-blocked polyurethane polymer network was applied to fabricate paper of high ink adhesive properties. In the case of the same external factors (gluing temperature, drying time, etc.), the surface sizing effect of paper samples (sizing with TBPU, polyvinyl alcohol and TBPU/PVA system) were evaluated by infrared spectroscopy, X-ray photoelectron spectroscopy, water contact angle measurements and scanning electron microscopy. Some of the pure cotton pulp paper with surface sizing treatment was treated via adhering inks to paper by spraying, smearing and soaking. The bonding strength was tested by peel-off tape tests, soaking tests, and simulated washing tests. The results showed that the water contact angle of the sized-paper increased from 67.6° to 89.7°. The mechanical properties had been greatly improved after treatment and SEM, AFM and XPS analyses indicated an increase in surface roughness and the oxygen-containing polar groups (C[double bond, length as m-dash]O, C-OH, -NH-COO- and COOH) enhanced the fixation of ink particles on the fiber surface. These tests indicated that the novel composite system of TBPU/PVA could endow specialty paper with superb mechanical properties and more than 90% ink retention rate. All these advantages of this composite system may contribute to its wide application in the fields of papermaking and printing.
ABSTRACT
BACKGROUND: We aimed to determine the role of the LINC00370/miR-222-3p/RGS4 axis in modulating the process of adipose-derived stem cell (ADSC) osteogenic differentiation. METHODS: We first evaluated the differential expression of LINC00370, miR-222-3p and RGS4 between normal and osteogenically induced ADSCs. Moreover, we transfected ADSCs with LINC00370 siRNA and an miR-222-3p inhibitor to determine the role of LINC00370 in modulating the process of ADSC osteogenic differentiation. Finally, we analyzed the dual-luciferase reporter gene to identify the relationship between LINC00370 and miR-222-3p. We first created osteoporotic rat models by ovariectomy (OVX) and treated with pcDNA-LINC00370. HE and immunohistochemical staining of OCN were performed to assess the changes in bone microarchitecture. RESULTS: LINC00370 and RGS4 expression was remarkably upregulated in the osteogenic ADSC group compared with the normal medium group. On the other hand, miR-222-3p expression was remarkably decreased in the osteogenic group compared with the normal medium group. Knockdown of LINC00370 reduced the osteogenic differentiation of ADSCs. Moreover, the inhibitor of miR-222-3p partially reversed the reduction of osteogenic differentiation by LINC00370 knockdown. Knockdown of LINC00370 reduced the expression of p-Akt and p-PI3K. The inhibitor of miR-222-3p partially reversed the reduction of the expression of p-Akt and p-PI3K by LINC00370 knockdown. A dual luciferase reporter assay indicated that LINC00370 can directly bind miR-222-3p. LINC00370 suppressed OP progression in OVX and partially upregulated OCN protein expression. CONCLUSION: Collectively, the above results confirm that LINC00370 promotes the process of ADSC osteogenic differentiation via the miR-222-3p/RGS4 axis. Moreover, LINC00370 could protect against OVX-induced OP.