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Secondary lymphedema is a chronic disease associated with deformity of limbs and dysfunction; however, conventional therapies are not curative. Adipose-derived stem cells (ADSCs) based therapy is a promising way, but a single transplantation of ADSCs has limited efficacy. In this study, ADSCs were engineered in vitro and then transplanted into the site of lymphedema. Yes-associated protein (YAP), a crucial regulator of Hippo pathway, plays an important role in regulating stem cell functions. We examined the YAP expression in a mouse tail lymphedema model, and found that transplanted ADSCs exhibited high expression level of YAP and a large number of YAP positive cells existed in lymphedema environment. In vitro, the downregulation of YAP in ADSCs resulted in higher expression levels of genes related to lymphangiogenesis such as Lyve-1, VEGFR-3 and Prox-1. In vivo, YAP-engineered ADSCs generated abundant VEGFR-3-positive lymphatic vessels and significantly improved subcutaneous fibrosis. These results indicated that the transplantation of pre-engineered ADSCs by manipulating YAP is a promising strategy for lymphatic reconstruction.

The impact of tumor mutations and the interplay of cytokines and chemokines on the immune response and clinical outcomes in uveal melanoma (UM) warrants further exploration. In our study, we delved into the correlation between genetic alterations and survival rates in a cohort of 188 UM patients, utilizing data from cBioPortal. We assessed the composition of immune cell populations within 80 UM tumors by examining RNA sequence-based gene expression data from The Cancer Genome Atlas (TCGA). Furthermore, we scrutinized the relationship between genetic mutations and the expression of cytokines and chemokines, as well as their influence on various immune cell subsets. Our investigation revealed a significant association between the presence of mutated GNAQ or SF3B1 genes and improved progression-free survival (PFS), disease-specific survival (DSS), and overall survival (OS) when compared to patients with non-mutated counterparts. In contrast, the presence of immune response gene mutations was associated with a detrimental effect on PFS, DSS, and OS. We also observed that the expression levels of cytokines and chemokines were positively linked to the infiltration of immune killer cells and inversely related to the populations of B cells and dendritic cells. Elevated expression levels of PDCD1, TNF, IL6, CXCL9, and CXCL10 were found to be correlated with reduced OS. Intriguingly, an increase in CD8+ T cell populations was associated with a poorer OS, a finding that warrants further investigation. These findings underscore the potential utility of cytokines/chemokines expression levels, immune cell subsets, and mutation status as critical biomarkers for the selection of patients who are most likely to benefit from immunotherapeutic interventions. Our research provides valuable insights that could guide the development of more targeted and effective treatment strategies for UM patients.

OBJECTIVES: The relationship between long working hours and the risk of mortality has been debated in various countries. This study aimed to investigate the association between long working hours and all-cause mortality in a large population-based cohort in China.METHODS: This retrospective cohort study (N=10 269) used a large, nationally representative data set [the China Health and Nutrition Surveys (CHNS)] from 1989 to 2015. Long working hours (≥55 hours per week) were compared to standard working hours (35–40 hours per week). The outcome measure was all-cause mortality. Hazard ratio (HR) for all-cause mortality was calculated from Cox proportional hazards regression models, with stratified analyses to assess differences in mortality risk among subgroups.RESULTS: Among the participants, 411 deaths (3.52 per 1000 person-years) occurred during a median follow-up of 11.0 (range 4.0–18.0) years. After adjusting for covariates, long working hours were associated with a significantly increased risk of all-cause mortality [HR 1.49, 95% confidence intervals (CI) 1.02–2.18]. Stratified analyses revealed that this association was present only among men (HR 1.78, 95% CI 1.15–2.75) and smoking participants (HR 1.57, 95% CI 1.05–2.57).CONCLUSION: This study provides evidence of an association between long working hours and all-cause mortality, which is specifically observed among men and smokers. Targeted interventions should be implemented to reduce excessive working hours and identify individuals at elevated risk, with support from labor organizations, policymakers, and employers.

Background/purpose: Temporomandibular joint (TMJ) osteoarthritis (TMJOA) is a chronic disease with progressive destruction of articular cartilage. This study aimed to explore the therapeutic effects of kartogenin on TMJOA via promoting the binding of core binding factor β (CBFβ) and runt-related transcription factor 1 (RUNX1). Materials and methods: Type II collagenase was injected into 35 8-week-old male Sprague Dawley rat TMJs to establish the TMJOA model. Kartogenin, or the CBFβ-RUNX1 complex inhibitor (Ro5-3335), was also delivered via intra-articular injection. Subchondral bone was analyzed by MicroCT. The hematoxylin-eosin, Safranin O, and toluidine blue O staining were used to observe histopathology. Immunohistochemical staining of proliferating cell nuclear antigen (PCNA), caspase-3 (CASP3), interleukin-1β (IL-1β), and collagen II (COL2) was performed. Results: TMJOA was established in rats by intra-articular injection of type II collagenase. The condylar cartilage and subchondral bone were damaged, with decreased PCNA and COL2 and increased CASP3 and IL-1 (P

Abstract Background Intravenous leiomyomatosis (IVL) is a rare and specific type of smooth muscle tumor that is histologically benign but has a malignant biological behavior. It is commonly associated with a history of uterine leiomyomas. Case presentation A 36-year-old woman, G1P1, presented to the hospital with left lower abdominal pain for 2 months and she has accepted hysteroscopic myomectomy about 1 year ago. Ultrasound venography, echocardiography and computed tomography venography (CTV) of inferior vena cava were performed, which revealed IVL located in left intramural myometrium walls growing along the left ovarian vein reaching the level of the lumbar 5-sacral 1 disc. Laparoscopic bilateral salpingo-oophorectomy and hysterectomyis were scheduled. The IVL in the left ovarian vein and parauterine venous plexus were detected and excised completely during surgery. IVL was diagnosed by postoperative pathology and immunohistochemistry. The patient recovered well after surgery. No surgical-related or anesthesia-related complications occurred.The 3-month follow-up CTV of inferior vena cava and echocardiography examination revealed normal. Conclusions The cause of IVL is unknown, this observation demonstrates that hysteroscopic myomectomy might lead to the occurrence of IVL.

In this experiment, Ti-44Al-9Nb-1Cr-0.2W-0.2Y alloy was prepared by the directional solidification method. The effect of different growth rates on tensile properties and microstructure orientation at high temperature was studied. Three kinds of alloys with different growth rates of 10 μm/s, 15 μm/s and 20 μm/s were prepared. The results show that the tensile properties of the alloy at 800 ℃ decrease with increasing growth rate, and recrystallization occurred at the position of intracrystal fracture in the microstructure. The size of columnar crystals decreases with the increase of the growth rate, increasing the number of grains and decreasing the orientation difference between the growth and axial directions as well as the preferred orientation of lamellar, and the anisotropy of the material, which leads to the obvious decrease of the tensile strength and plasticity. Combined with electron backscattering diffraction test results, the lamellar orientation of the effective parts of the three specimens after high temperature stretching was studied. It was found that the axial preferred orientation of the alloy specimens decreased obviously with the increase of the growth rate, and the orientation became disorderly and the uniformity of lamellar thickness decreased gradually with the increase of the growth rate. In addition, it was found that a new single-phase γ phase is formed in the microstructure after high temperature stretching, and the distribution range increased with the increase of the growth rate, which seriously degraded the axial preferred orientation of the alloy. It can be concluded that the directionally solidified alloy with a growth rate of 10 μm/s has better microstructure orientation and high temperature tensile properties.

This paper presents a novel dynamic frequency assignment (DFA) technique for cognitive radio cellular networks (CRCNs) using hysteretic noisy chaotic neural network (HNCNN). HNCNN is a novel neural network that combines the advantages of stochastic chaotic simulated annealing and hysteretic dynamics to achieve performance improvements in dynamic frequency assignment. In DFA technique, an existing energy function is introduced, which avoids causing harmful interference to primary users (PUs) according to the real-time interference frequency table. In a CRCN, the introduced energy function also avoids causing mutual interferences among cells, considers the number of required frequencies for each cell, and simultaneously minimizes the total number of assigned frequencies to improve spectrum utilization. In the end, a typical 49-cell CRCN with 70 licensed frequencies is examined to demonstrate the validity of the proposed technique. And the results also show that HNCNN outperforms noisy chaotic neural network (NCNN) according to convergence speed and the rate of optimal solution.

This work studied Mo-TiC-xCr (x = 0.0, 0.5, 1.0 wt.%) matrix composites with different component gradients prepared by Spark Plasma Sintering (SPS). The high-temperature oxidation test was conducted at 1200 ℃ in the atmosphere to study the influence of Cr on the high-temperature oxidation behavior of TiC-reinforced Mo matrix composites. The phase composition and morphology of the oxide film were analyzed using X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy dispersive spectroscopy (EDS), and the goal was to determine the effect of the Cr content on the high-temperature oxidation properties of the Mo-TiC-xCr (x = 0.0, 0.5, 1.0 wt.%) matrix composites. The results showed that with increasing oxidation time, the oxide film on the surface of Mo alloy will crack and fall off easily, and the porosity gradually increases. Oxygen underwent vigorous oxidation through the pores and the inside of the matrix, and a protective MoO2 internal oxide film disappeared. With increasing Cr content, the high-temperature oxidation performance of the Mo alloy improved, the thickness of the oxide film decreased, warping of the surface oxide film was inhibited, the porosity decreased, and volatilization of MoO3 was inhibited. After oxidation, the surface oxide film was mainly composed of TiO2, MoO3, Cr2O3 and Cr2(MoO4)3 phases. The TiC particles dispersed in the matrix were oxidized to TiO2 to inhibit the oxidation of the alloy. The Cr formed a protective oxidation film of Cr2O3, which effectively reduced the porosity and delayed the volatilization of the MoO3, thus improving its oxidation performance.

AbstractCapsicum chinense is one of the best ingredients for making chili sauces and extracting capsaicin. In this study, we identified 59 genes associated with shikimic acid, phenylpropane, unsaturated fatty acids, phenylalanine, valine, leucine, isoleucine and other metabolic pathways based on pepper genome. In the present study, 58 of the 59 genes involved in capsaicin synthesis were found to be unevenly distributed on 11 chromosomes, and several genes with the same number of exons and high homology were found to be clustered in a duplication region of the chromosome. The promoter regions of these genes were predicted and analyzed, and multiple gene promoters were found to contain MYB binding sites, which provided a reference for the subsequent exploration of MYB target genes. At the same time, the expression levels of genes related to capsaicin synthesis were analyzed based on different transcriptomes, and it was found that these genes showed significant differences in different plant development stages and different tissues. The results of this study will be helpful to further study the synthesis mechanism of capsaicin in Capsicum chinense and the functional relationship between genes.

In this paper, fracture morphology observation, microstructure analysis, standard corrosion test, and other experimental methods are used to analyze the causes of corrosion and cracking of steam turbine blades (0Cr19Ni9) produced by a certain company. The results showed that cracks appeared during the operation of the blade. A large number of dimples were observed under the scanning electron microscope, almost all of which were shear dimples; at the same time, fatigue bands were also distributed in them. The internal cause of the cracks is the long-term service, which causes the carbon and the alloy to undergo a diffusion reaction to form carbon-rich areas and carbides. They are thermally corroded in the service environment, and the carbon-rich zone is reduced, which reduces the strength of the zone; carbides accumulate at the grain boundary, causing groove-shaped defects at the grain boundary to form a cutting effect. It is easy to form a source of fatigue cracks. The external cause is that the material is subjected to transverse stress for a long time during operation, which leads to the generation of cracks. This article analyzes the failure causes of the blade and proposes related solutions, which have important reference value for production practice.

In this paper, the Titanium carbide/Molybdenum (TiC/Mo) alloy was prepared by spark plasma sintering (SPS). The oxidation process of the TiC/Mo alloy at different oxidation temperatures was studied, and the oxidation mechanism was discussed in depth. The focus is on the influence of the introduction of TiC particles on the high-temperature oxidation properties of Mo alloys. The phase composition and morphology of the oxide film were analyzed by means of X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy dispersive spectroscopy (EDS). The results showed that, after oxidation, the surface oxide film is mainly composed of Titanium dioxide (TiO2), Molybdenum dioxide (MoO2), Molybdenum trioxide (MoO3) and Molybdenum oxide hydrate (MoO3(H2O)2) phases. As the oxidation temperature increases, the surface of the oxide film will warp, and thereby increase porosity. The dense MoO2 will form a protective inner oxide layer and inhibit further progress of the TiC/Mo alloy. Oxygen will undergo violent oxidation through the pores and the inside of the matrix, and the protective MoO2 internal oxide film will disappear. TiC particles dispersed in the matrix will be oxidized to form TiO2, which will be gradually deposited on the surface of the oxide film, hindering the diffusion of oxygen to the matrix. The quantity loss during the entire oxidation process is significantly reduced. Therefore, the introduction of TiC can greatly improve the oxidation resistance of Mo alloys.

The research focuses on the high temperature oxidation resistance of martensitic heat-resistant steel. A new type of martensitic heat-resistant steel was developed with the addition of Al and Cu, and the oxidation behavior of the new martensitic heat-resistant steel at 650 °C and 700 °C was analyzed. The high temperature oxidation kinetics curves of new martensitic heat-resistant steel at 650 °C and 700 °C were determined and plotted by cyclic oxidation experiment and discontinuous weighing method. XRD technique was applied to qualitatively analyze the surface oxide of the material after oxidation. The surface and cross-section morphology of the material were observed by field emission scanning electron microscope (SEM) and energy dispersive spectrometer (EDS), and the oxidation mechanism at high temperature was analyzed. The results show that the oxide film can be divided into two layers after oxidation at 650 ºC for 200 h. The outer oxide film is mainly composed of Fe and Cu oxides, and the inner oxide film is mainly composed of Al2O3, SiO2 and Cr2O3. After oxidation at 700 ºC for 200 h, the outer layer is mainly composed of Fe, Cu, Mn oxides, and the inner layer is mainly composed of Cr, Al and Si oxides. The addition of a small amount of Cu promotes the diffusion of Al and Si elements, facilitates the formation of Al2O3 and SiO2, and improves the high-temperature oxidation resistance of martensitic heat-resistant steel.

A new type of hot working die steel was designed by using JMatPro, and high-temperature oxidation tests were carried out in the ambient atmosphere at 600 ℃ and 700 ℃. The heat treatment process and oxidation mechanism of the designed 4Cr4Mo2NiMnSiV steel were studied in detail. XRD, SEM and EDS were used to analyze the crystallographic phases, surface and cross-section morphologies of the oxide films. The results show that the main phases in the 4Cr4Mo2NiMnSiV steel were γ and α + δ. During the high-temperature oxidation, oxidation of the Fe outer layer and Cr inner layer occurred. After oxidation at 600℃, the surface oxidation layer comprised a monolayer with an uneven morphology. The surface oxide film had two layers after oxidation at 700℃. The outer oxide layer mainly contained Fe2O3 and Fe3O4, while the inner oxide layer mainly contained Cr2O3. The microstructure was relatively regular and had a significant effect on the protection of the metallic matrix. When oxidized, the 4Cr4Mo2NiMnSiV alloy steel easily formed protective layers, such as Cr2O3 and SiO2, so that the test steel had excellent oxidation resistance at high temperatures.

Due to the lack of blood vessels, nerves and lymphatic vessels, the capacity of articular cartilage to heal is extremely limited. Once damaged, it is urgent for articular cartilage to repair the injury. In recent years, there has been an increase in cartilage tissue engineering studies. Self-assembling peptide hydrogel as a kind of hydrogels composed of peptides and water is widely used in cartilage tissue engineering. Under noncovalent interactions such as electrostatic interaction, hydrophobic interaction, hydrogen bonding and pi-pi stacking force, peptides self-assemble into three-dimensional (3D) structures that mimic the natural extracellular matrix and allow cells to grow, proliferate and differentiate. Because SAPHs have excellent biocompatibility and biodegradability, variable mechanical properties, low immunogenicity, injectability, and the ability to load cells and bioactive substances, many researchers utilized them to promote the repair and regeneration of articular cartilage after damage. Therefore, the purpose of this review is to sum up the composition, injury characteristics, and treatments of articular cartilage, as well as the action of SAPHs in repairing articular cartilage damage.

Abstract Lung cancer remains the leading cause of cancer deaths worldwide. Although low-dose spiral computed tomography (LDCT) screening is used for the detection of lung cancer in a high-risk population, false-positive results of LDCT remain a clinical problem. Here, we developed a blood test of a novel panel of three established lung cancer methylation biomarkers for lung cancer detection. Short stature homeobox 2 gene (SHOX2), ras association domain family 1A gene (RASSF1A), and prostaglandin E receptor 4 gene (PTGER4) methylation was analyzed in a training cohort of 351 individuals (197 controls, 154 cases) and validated from an independent cohort of 149 subjects (89 controls, 60 cases). The novel panel biomarkers distinguished between malignant and benign lung disease at high sensitivity and specificity: 87.0% sensitivity [95% CI 80.2–91.5%], 98.0% specificity [95% CI 94.9–99.4%]. Sensitivity in adenocarcinoma, squamous cell carcinoma, small cell lung cancer, and other lung cancer was 89.0%, 87.5%, 85.7%, and 77.8%, respectively. Notably, cancer patients in stage I and II showed high diagnostic sensitivity at 82.5% and 90.5%, respectively. Moreover, the diagnostic efficiency did not show bias toward age, gender, smoking, and the presence of other (nonlung) cancers. The performance of the panel in the validation cohort confirmed the diagnostic value. These findings clearly showed that this panel of DNA methylation biomarkers was effective in detecting lung cancer noninvasively and may provide clinical utility in stand-alone or in combination with current imaging techniques to improve the diagnosis of lung cancer.

Background: Target therapies play more and more important roles in gastrointestinal stromal tumors (GISTs) and melanoma with the advancement of clinical drugs that overcome the resistance caused by gene mutations. c-KIT gene mutations account for a large portion of GIST patients, which are known to be sensitive or resistant to tyrosine kinase inhibitors. However, the role rare mutations play in drug efficacy and progression-free duration remains elusive.Methods: Two rare mutations were identified using Sanger sequencing from the GIST and melanoma cases. Cell experiments were further carried out to demonstrate their role in the imatinib resistance.Results:c-KIT c.1926delA p.K642S*FS mutation in primary and recurrent GIST patients and c-KIT c.1936T>G p.Y646D point mutation in melanoma patients in exon 13 were first demonstrated to be novel targets resistant to imatinib agent.Conclusion:c-KIT mutations c.1926delA and c.1936T>G in exon 13 are clinically significant targets that exhibit resistance to imatinib. This study provides guidance to GIST and melanoma treatments.

Abstract Background Lung cancer remains the leading cause of cancer deaths across the world. Early detection of lung cancer by low-dose computed tomography (LDCT) can reduce the mortality rate. However, making a definitive preoperative diagnosis of malignant pulmonary nodules (PNs) found by LDCT is a clinical challenge. This study aimed to develop a prediction model based on DNA methylation biomarkers and radiological characteristics for identifying malignant pulmonary nodules from benign PNs. Methods We assessed three DNA methylation biomarkers (PTGER4, RASSF1A, and SHOX2) and clinically-relevant variables in a training cohort of 110 individuals with PNs. Four machine-learning-based prediction models were established and compared, including the K-nearest neighbors (KNN), random forest (RF), support vector machine (SVM), and logistic regression (LR) algorithms. Variables of the best-performing algorithm (LR) were selected through stepwise use of Akaike’s information criterion (AIC). The constructed prediction model was compared with the methylation biomarkers and the Mayo Clinic model using the non-parametric approach of DeLong et al. with the area under a receiver operator characteristic curve (AUC) analysis. Results A prediction model was finally constructed based on three DNA methylation biomarkers and one radiological characteristic for identifying malignant from benign PNs. The developed prediction model achieved an AUC value of 0.951 in malignant PNs diagnosis, significantly higher than the three DNA methylation biomarkers (0.912, 95% CI:0.843–0.958, p = 0.013) or Mayo Clinic model (0.823, 95% CI:0.739–0.890, p = 0.001). Validation of the prediction model in the testing cohort of 100 subjects with PNs confirmed the diagnostic value. Conclusion We have shown that integrating DNA methylation biomarkers and radiological characteristics could more accurately identify lung cancer in subjects with CT-found PNs. The prediction model developed in our study may provide clinical utility in combination with LDCT to improve the over-all diagnosis of lung cancer.

In the process of acute resistance exercise, repeated variation in motion intensity can lead to muscle fatigue and heart failure. Therefore, acquiring the interval of motion intensity variation in time the training pattern and effect can be improved by acquiring the interval of motion intensity variation. In order to achieve this goal, an improved Inception-V3 model is proposed for motion intensity variation interval estimation. The MIVIE(Motion Intensity Variation Interval Estimation) dataset consisting of Strong, Moderate, Weak groups achieve centralized and uninterrupted collection. Then, the multi-modal fusion vectors of time-frequency eigenvalues are stacked up to $227\times227$ grayscale images fed into improved inception-CNN. Finally, the manipulator’s trajectory optimization is completed under the guidance of ATO-DQN (Adaptive Trajectory Optimization-Deep Q Network) algorithm based on the motion intensity interval estimation. This work can improve the non-stationary effect of motor speed caused by changes in motion intensity during rehabilitation, which can better guarantee the safety of patients.

Objective. To compare the efficacy of febuxostat and allopurinol in the treatment of chronic kidney disease (CKD) at stages 3∼5 with hyperuricemia. Methods. A total of 100 patients with stage 3 to 5 CKD with hyperuricemia in our hospital from July 2018 to December 2019 were selected and divided into the control group (n = 50) and the experimental group (n = 50) according to the random number expression method, the control group on the basis of conventional treatment with allopurinol treatment, the experimental group based on conventional treatment using the febuxostat be treatment. The clinical efficacy, incidence of adverse reactions, and renal function indexes, blood urea nitrogen (BUN), serum creatinine (Scr), serum sodium (Na), serum potassium (K), and serum uric acid (UA) before and after treatment were compared between the two groups. Results. The total effective rate of the experimental group and the control group was 82.00% and 78.00%, respectively, with little difference (P>0.05); compared with before treatment, BUN, Scr, and UA of the two groups were decreased (P

The research is focused on a novel aluminum and copper-containing heat-resistant steel. The steel was designed by the material performance simulation software JmatPro, performed high-temperature oxidation tests at 650 °C and 700 °C atmospheric conditions, and analyzed the high-temperature oxidation processes and its mechanisms.The phase transtions and surface morphology of the oxide films were studied using X-ray diffraction (XRD), electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS). The results showed that the equilibrium phase of the test steel is composed of γ phase and δ phase at 1050 °C and tranforms to tempered martensite and δ-Fe mixed structure after heat treatment. The preferential oxidation of Fe and Cr and the internal oxidation of Al occurred during the high temperature oxidation of the test steel. The oxide films were formed with various shape and weak bonding properties after high-temperature oxidation at 650℃. To the contrary, the oxide films more regular and evenly distributed, and has a certain protective effect after high-temperature oxidation at 700 ℃. The oxide films were divided into two layers, Fe2O3 is main element in the outer layer, the inner layer is mainly consisting the oxide of Cr. However, the addition of Cu element can promote the diffusion of Al and Si elements, which is beneficial to the formation of Al2O3 and SiO2 protective oxide films and excellent in high temperature oxidation resistance.

Acquired resistance to epidermal growth factor receptor (EGFR)‐tyrosine kinase inhibitors (TKIs) is a prevalent clinical problem in the management of advanced non‐small‐cell lung cancer (NSCLC) with TKI‐sensitizing mutations in the EGFR gene. Third‐generation EGFR‐TKIs have demonstrated potent activity against TKI resistance mediated by the EGFR T790M mutation, and standard rebiopsy and liquid biopsy are utilized to assess the T790M status of the NSCLC patients who experienced progressive disease (PD). Here, we conducted a retrospective study to assess 375 patients whose initial biopsy indicated a TKI‐sensitizing mutation (either EGFR 19del or L858R) and who developed PD after treatment with first‐generation TKIs, and assayed for T790M status. We adopted a combination approach in which tissue rebiopsy is preferred, utilizing liquid biopsies when tissue rebiopsy is not feasible. We analyzed the potential predictive clinical factors affecting T790M detection, evaluated the standard rebiopsy and liquid biopsy methods in T790M genotyping, and reported the clinical performance of osimertinib. Our results suggested that primary EGFR 19del, brain metastasis, and longer progression‐free survival of initial EGFR‐TKI treatment are associated with acquired T790M resistance. T790M‐positive patients significantly benefited from osimertinib. In conclusion, the real‐world clinical adoption of the combination approach with both tissue rebiopsy and liquid biopsy for T790M genotyping may provide significant benefits to patients who have developed PD after first‐generation TKI treatments.

Oral squamous cell carcinoma (OSCC) is the most prevalent malignancy in head and neck cancer, with high recurrence and mortality. Early diagnosis and efficient therapeutic strategies are vital for the treatment of OSCC patients. Exosomes can be isolated from a broad range of different cell types, implicating them as important factors in the regulation of human physiological and pathological processes. Due to their abundant cargo including proteins, lipids, and nucleic acids, exosomes have played a valuable diagnostic and therapeutic role across multiple diseases, including cancer. In this review, we summarize recent findings concerning the content within and participation of exosomes relating to OSCC and their roles in tumorigenesis, proliferation, migration, invasion, metastasis, and chemoresistance. We conclude this review by looking ahead to their potential utility in providing new methods for treating OSCC to inspire further research in this field.

With the continuous development of ship technology, the usage environment of some parts has changed, with higher requirements for materials and preparation technology being put forward. Some traditional structural materials have do not meet the actual working conditions of ships, which necessitates development of new materials and research on their preparation technology. Owing to its high strength and stable mechanical properties at high temperature, molybdenum base alloy is expected to replace nickel base alloy and aluminum base alloy the primary structural material in the development of ships. Under the conventional method, the impurity elements is quite complex and there are limitations in the shape of the formed parts. This experiment uses spherical pure molybdenum powder as raw material. The effects of laser power, powder thickness, scanning speed and scanning distance on the microstructure of formed parts during selective laser melting process were studied and the optimum process parameters were determined. Laser power and scanning speed can seriously affect the quality of the forming parts. In this experiment, by comparing the density and internal holes of the forming parts under different process parameters, the best preparation process for the forming parts was determined: laser power 325 watts, scanning speed 400 mm s ^−1 , powder thickness 30 μ m, scanning distance 40 μ m. Meanwhile, the forming workpiece density is the largest, up to 94.92%.

The content and component of glucosinolates in edible stems and leaves of eight Chinese kale varieties from Japan and eight varieties from China were determined by HPLC-MS. Simultaneously, the expression levels of glucosinolate biosynthesis pathway genes from four varieties with high and low total glucosinolate contents were analyzed by the qRT-PCR method. Four types of aliphatic glucosinolates (A-GLSs: GRA, SIN, GNA and GER) and indole glucosinolates (I-GLSs: 4-HGBS, GBS, 4-MGBS and NGBS) were detected in the stems and leaves of 16 varieties, and no aromatic glucosinolates (R-GLSs) were detected. A-GLSs account for more than 80.69% of the total content of total glucosinolates (T-GLSs), in which GNA and GRA are the main components of stems and leaves. Among Japanese varieties, QB1 has higher content of A- and T-GLSs, while that of XLB was lower; however, the corresponding varieties were ZH and DSHH in Chinese varieties. Among the above four varieties, the expression levels of SOT16, CYP83B1, SOT17, CYP83A1 and MAM1 genes were significantly higher in the varieties with higher GLSs; the expression levels of SOT16 and CYP83B1 were consistent with the content of I-GLSs; and SOT17, CYP83A1 and MAM1 expression levels were consistent with A-GLSs content. At the same time, the expression levels of SOT16 and CYP83B1 in the leaves were higher than those in the stems. CYP83A1 and MAM1 genes were less expressed in the leaves than in the stems of lower content varieties. It is speculated that these genes may be the key genes regulating GLS biosynthesis in Chinese kale.

Although sulfite, a by-product of the degradation of many sulfur compounds, is highly reactive and can cause damage to DNA, proteins and lipids, comparatively little is known about the regulation of sulfite-oxidizing enzyme (SOEs) expression. Here we have investigated the regulation of SOE-encoding genes in two species of α-Proteobacteria, Sinorhizobium meliloti and Starkeya novella, that degrade organo- and inorganic sulfur compounds, respectively, and contain unrelated types of SOEs that show different expression patterns. Our work revealed that in both cases, the molecular signal that triggers SOE gene expression is sulfite, and strong up-regulation depends on the presence of a sulfite-responsive, cognate Extracytoplasmic function (ECF) sigma factor, making sulfite oxidation a bacterial stress response. An additional RpoE1-like ECF sigma factor was also involved in the regulation, but was activated by different molecular signals, taurine (Sm) and tetrathionate (Sn), respectively, targeted different gene promoters, and also differed in the magnitude of the response generated. We therefore propose that RpoE1 is a secondary, species-specific regulator of SOE gene expression rather than a general, conserved regulatory circuit. Sulfite produced by major dissimilatory processes appeared to be the trigger for SOE gene expression in both species, as we were unable to find evidence for an increase of SOE activity in stationary growth phase. The basic regulation of bacterial sulfite oxidation by cognate ECF sigma factors is likely to be applicable to three groups of alpha and beta-Proteobacteria in which we identified similar SOE operon structures.

The surface of steel substrate was pretreated by nickel plating and Aluminum/nickel-plated steel bimetal was prepared by compound casting. After liquid aluminum was casted on the surface of the nickel-plated steel, it was placed in a heat preservation device and temperature set at 760 °C. In the compound casting process of molten aluminum and nickel-plated steel, good metallurgical bonding is formed between aluminum and steel by means of diffusion. Subsequently, the microstructure of the aluminum/nickel-plated steel bimetal was examined using Scanning Electron Microscopy (SEM) and Energy Dispersive Spectroscopy (EDS) techniques. The phase composition of the intermediate layer was analyzed by x-ray diffraction (XRD). Further, the bonding properties and fracture mechanism of the intermediate layer were analyzed by measuring the corresponding Vickers microhardness and shear strength. The results show that the intermediate layer is divided into two layers. In addition, intermetallic compounds appear in the intermediate layer; Al _5 Fe _2 , near the steel side, and Al _8 Fe _2 Si, near the aluminum side. The main phases in the intermediate layer are α -Al, α -Fe, Al _5 Fe _2 , Al _5 FeSi and Al _8 Fe _2 Si. The microhardness of the intermediate layer of the aluminum/steel bimetal is higher than that of both the aluminum matrix and steel matrix. It is observed that the thickness of the intermediate layer of the aluminum/nickel-plated steel bimetal increases with the increase of the holding time. When the holding time was 15 min, the intermediate layer of the aluminum/nickel-plated steel bimetal exhibits the highest shear strength, i.e. 13.4 MPa. The fracture of the aluminum/steel bimetal is a brittle fracture, and starts from the intermediate layer. The results show that nickel plating on steel substrate can obviously improve the casting properties of an aluminum/steel bimetal.

Ultrasonic additive manufacturing (UAM) is an advanced additive manufacturing technique that utilizes ultrasonic energy to rapidly joining thin metal tapes into solid parts in a layer accumulating manner. In this study, the effects of processing parameters on the bond properties of UAM samples were investigated via peel tests, linear weld density (LWD) measurements, microhardness tests and EBSD. The results reveal that, in terms of the overall tendency, the peeling strength and LWD increase with the increasing amplitude and normal force settings. However, a parameter threshold phenomenon and two different mechanisms that affect the bond properties were also observed. Furthermore, the microstructure evolution results show that the development of the interface is closely related to the applied parameters, which can also well explain the bond property variations and the parameter threshold phenomenon.

The flow stress behavior of high-strength low-alloy (HSLA) steel at different true strains was studied using a hot compression test. The effect of dynamic recrystallization (DRX) on the transformed ferrite microstructures was investigated with electron backscatter diffraction (EBSD). The EBSD analysis indicated that the fraction of high-angle grain boundaries (HAGBs) and DRX increased with increasing true strain. The low-angle grain boundaries (LAGBs) were gradually transformed into HAGBs with increasing DRX degree. When the true strain was increased to 0.916, the fraction of HAGBs increased to 85% and the fraction of DRX increased to 80.3%. The relatively high fraction of HAGBs was related to the complete DRX. The dislocations and substructures in the tested steel at different true strains were characterized by transmission electron microscopy (TEM). TEM observation shows that the nucleation of the dynamically recrystallized grains occurred by the bulging of the original grain boundaries. The DRX nucleation mechanism of the HSLA steel is the strain-induced grain boundary migration mechanism.

The flow behavior of Nb–V–Mo microalloyed steel at different deformation parameters was investigated using isothermal compression tests. The microstructures of the specimens after deformation were observed through the use of a metallographic microscope. The results indicated that the deformation temperature had a significant effect on the grain size of the deformed specimen and the average size of grains increases with corresponding increase in temperature in the range of 800 °C–1100 °C. The dislocations and substructures of the specimens after deformation were characterized using TEM. The bulged grain boundary was observed through TEM when the specimen was deformed at 1100 °C and 1 s ^−1 . The effect of the strain rate on the dynamic recrystallization behavior was investigated using electron backscatter diffraction (EBSD). The EBSD results indicated that the fraction of low-angle grain boundaries decreased with a corresponding decrease in strain rate, and the average sub-boundary misorientation increased with a decreasing strain rate. The continuous dynamic recrystallization mechanism was determined through EBSD analysis.

AIMS:In this study, we determined whether different subtypes of epidermal growth factor receptor (EGFR) exon19 mutation are associated with the therapeutic effect of EGFR-tyrosine kinase inhibitors (TKIs) on advanced non-small cell lung adenocarcinoma. METHODS:A total of 122 patients with stage III or IV non-small cell lung adenocarcinoma were retrospectively reviewed. Clinical characteristics of these patients, including progression-free survival (PFS) outcome for EGFR-TKI treatment, were analyzed. RESULTS:According to the mutation pattern, we classified the in-frame deletions detected on EGFR Exon19 into three different types: codon deletion (CD), with a deletion of one or more original codons; codon substitution and skipping (CSS), with a deletion of one or two nucleotides but the residues could be translated into a new amino acid without changing following amino acid sequence; CD or CSS plus single nucleotide variant (SNV) (CD/CSS+SNV), exclude CD or CSS, there's another SNV nearby the deletion region. The clinical characteristics of three groups were analyzed and as a result, no significant difference was found. By comparing the average number of missing bases and amino acids of the three mutation subtypes, it could be discovered that the number of missing bases and amino acids of the three mutation subtypes is diverse, and group CSS> group CD> group CD/CSS+SNV. Finally, survival analysis was performed between three groups of patients. The median PFS of group CD, group CSS and group CD/CSS+SNV was 11 months, 9 months and 14 months respectively. There was a distinct difference in the PFS between group CSS and group CD/CSS+SNV (P = 0.035

[001] oriented DD6 alloy was prepared by directional solidification in this experiment. γ ′ phase precipitation phase structure of different morphology and size was obtained by different high temperature ageing heat treatment processes. Through this experiment, the feasibility of improving high temperature performance by adjusting the heat treatment process to change the microstructure of the single crystal was explored. The as-cast DD6 is first subjected to standard heat treatment(SHT). The single crystal sample after the standard heat treatment was further kept at 900 °C–1300 °C for 10 min, 30 min and 1 h, finally air-cooled respectively. Heat treatment process of DD6 was simulated using Jmatpro software. The individual phase transition temperatures of the alloy were determined by DSC experiments. And the size and volume fraction of precipitated phase of the alloy were estimated using Image-Pro Plus software. It is concluded that the microstructure of the alloy obtained after holding at 1100 °C for 30 min after standard heat treatment has the most uniform microstructure distribution.