Search

In this study, we investigate the impact of COVID-19 on academic achievement in Texas public schools. Demographic and Grade 5 STAAR test data were collected from 1155 public school districts for 2018–2019 and 2020–2021. Multiple regression was adopted to analyze the differences between rural and non-rural districts, as well as the impact of demographic characteristics on students' achievement. The results reveal significant differences in demographic characteristics between the two academic years, with non-rural districts exhibiting a greater decline in academic achievement than rural districts. Additionally, the findings suggest that higher teacher salaries correlate with better academic performance across various subjects and that English learners require additional support to acquire content knowledge and skills. We further confirm that the COVID-19 pandemic has disrupted the academic learning experience of Texas students, with rural districts displaying more resilience than non-rural districts. [ABSTRACT FROM AUTHOR]

The present study aimed to evaluate the psychometric properties and measurement invariance of the motivated and self‐regulation strategies for online learning (MSSOL) instrument. Data were collected from a sample of 1100 college students from a Chinese university. Factor analysis revealed favorable psychometric properties of the MSSOL. Furthermore, strong evidence was found to support the configural, metric, scalar, and strict invariance across gender groups, indicating the appropriate utilization of the MSSOL in accurately assessing online English learning motivation and self‐regulated learning (SRL) strategies among Chinese college students of both genders. This study represents a significant advancement in the measurement of motivation and SRL in the context of online English as a Foreign Language (EFL) instruction, particularly in light of the ongoing COVID‐19 pandemic. Implications for future research are discussed. [ABSTRACT FROM AUTHOR]

The findings and conclusions of this study are similar to those of other studies conducted on patient perspective.[11],[12] To patients, low-risk is not "no-risk", and "the C-word" terminology is still used to describe low-risk PTC. The most current national cancer statistics in China estimated 202,600 new thyroid cancer cases (incidence 13.37/10 SP 5 sp persons) and 8300 deaths in 2016.[1] The annual percentage increase in thyroid cancer incidence of was 17.7% in women between 2000 and 2016. [Extracted from the article]

• ET program boosts english proficiency in listening, reading, and writing/translation. • Group discussions and authentic English-speaking environment increased intercultural communication competence. • Teachers suggest using more advanced curriculum and textbooks. • ET program is successful in enhancing english language growth. • Incorporating ESP and ICC strategies in english courses is useful. This study examined the impact of an English talent (ET) program on the English language growth of college students in China. Using mixed methods, the researchers found that the ET program had a statistically significant impact on participants' English proficiency scores across all subtests (i.e., listening, reading, and writing/translation) compared to those of a group of students enrolled in traditional English courses. ET teachers' reflections indicated that the program improved their students' listening, speaking, reading, and writing skills and prepared them to compete in national English competitions. The study highlights the effectiveness of ET programs in English language education at the college level. [ABSTRACT FROM AUTHOR]

Uniquely capable of simultaneous imaging of the hemoglobin concentration, blood oxygenation, and flow speed at the microvascular level in vivo, multi-parametric photoacoustic microscopy (PAM) has shown considerable impact in biomedicine. However, the multi-parametric PAM acquisition requires dense sampling and thus a high laser pulse repetition rate (up to MHz), which sets a strict limit on the applicable pulse energy due to safety considerations. A similar limitation is shared by high-speed PAM, which also uses lasers with high pulse repetition rates. To achieve high quantitative accuracy besides good structural visualization at low levels of laser fluence in PAM, we have developed a new, sparse coding-based two-step denoising technique. In the setting of intravital brain imaging, we demonstrated that this unsupervised learning approach enabled the reduction of the laser fluence in PAM by 5 times without compromise of the image quality (structural similarity index measure or SSIM: >0.92) and the quantitative accuracy (errors: <4.9%). Offering a significant relaxation in the requirement of PAM on laser fluence while maintaining the quality of structural imaging and accuracy of quantitative measurements, this sparse coding-based approach is expected to facilitate the application and clinical translation of multi-parametric PAM and high-speed PAM, which have a tight photon budget due to either safety considerations or laser source limitations. [ABSTRACT FROM AUTHOR]

Liver-expressed antimicrobial peptide 2 (LEAP2) is a member of the antimicrobial peptides family and plays a key role in the innate immune system of organisms. LEAP2 orthologs have been identified from a variety of fish species, however, its function in primitive vertebrates has not been clarified. In this study, we cloned and identified Lc-LEAP2 from the primitive jawless vertebrate lamprey (Lethenteron camtschaticum) which includes a 25 amino acids signal peptide and a mature peptide of 47 amino acids. Although sequence similarity was low compared to other species, the mature Lc-LEAP2 possesses four conserved cysteine residues, forming a core structure with two disulfide bonds between the cysteine residues in the relative 1–3 (Cys 58 and Cys 69) and 2–4 (Cys 64 and Cys 74) positions. Lc-LEAP2 was most abundantly expressed in the muscle, supraneural body and buccal gland of lamprey, and was significantly upregulated during LPS and Poly I:C stimulations. The mature peptide was synthesized and characterized for its antibacterial activity against different bacteria. Lc-LEAP2 possessed inhibition of a wide range of bacteria with a dose-dependence, disrupting the integrity of bacterial cell membranes and binding to bacterial genomic DNA, although its inhibitory function is weak compared to that of higher vertebrates. These data suggest that Lc-LEAP2 plays an important role in the innate immunity of lamprey and is of great value in improving resistance to pathogens. In addition, the antimicrobial mechanism of LEAP2 has been highly conserved since its emergence in primitive vertebrates. • Lc-LEAP2 was cloned from the Lethenteron camtschaticum and was significantly overexpressed after multi-stimulation. • Lc-LEAP2 was abundantly expressed in the muscle, supraneural body and buccal gland. • Lc-LEAP2 possessed inhibition of bacteria with a dose dependence while its inhibitory function was weak. • Ancestral characteristics and functions of the LEAP2 were clarified. [ABSTRACT FROM AUTHOR]

Photoacoustic microscopy (PAM) leverages the optical absorption contrast of blood hemoglobin for high-resolution, multi-parametric imaging of the microvasculature in vivo. However, to quantify the blood flow speed, dense spatial sampling is required to assess blood flow-induced loss of correlation of sequentially acquired A-line signals, resulting in increased laser pulse repetition rate and consequently optical fluence. To address this issue, we have developed a sparse modeling approach for blood flow quantification based on downsampled PAM data. Evaluation of its performance both in vitro and in vivo shows that this sparse modeling method can accurately recover the substantially downsampled data (up to 8 times) for correlation-based blood flow analysis, with a relative error of 12.7 ± 6.1 % across 10 datasets in vitro and 12.7 ± 12.1 % in vivo for data downsampled 8 times. Reconstruction with the proposed method is on par with recovery using compressive sensing, which exhibits an error of 12.0 ± 7.9 % in vitro and 33.86 ± 26.18 % in vivo for data downsampled 8 times. Both methods outperform bicubic interpolation, which shows an error of 15.95 ± 9.85 % in vitro and 110.7 ± 87.1 % in vivo for data downsampled 8 times. [ABSTRACT FROM AUTHOR]

A microwave photonic time division multiplexing scheme is proposed and experimentally demonstrated for quasi-distributed demodulation of the cascaded fiber ring resonators (FRRs) in series. By arranging proper delay, the temporal pulse train of each FRR transformed from the whole frequency response can be recognized and separated in time domain. After extracting a specific temporal pulse train, the frequency response of the corresponding FRR is recovered by applying zero padding and fast Fourier transform (FFT), for which the reconstructed frequency resolution is improved and the spectral overlap in original frequency response is eliminated. Three situations with different delay lengths are performed to illustrate the contribution of delay to the multiplexing capability. Three FRRs are cascaded for experimentally verifying the multiplexing scheme, whose frequency responses are separately obtained and utilized for independent temperature sensing. The experimental results indicate that the microwave photonic time division multiplexing achieves the independently quasi-distributed demodulation of the cascaded FRRs with the temperature sensitivity of 49.1 kHz / ∘ C at about 4 GHz. By accurately allocating the staggered time slots, such scheme could extremely improve and arbitrarily adjust the spatial resolution, reduce the power consumption and increase the multiplexing capability, rendering a universal strategy for the multiplexing of other cavity ring-down systems. • Propose microwave photonic time division multiplexing for quasi-distributed sensing. • Alternately allocate exclusive time slots for each FRR to improve spatial resolution. • Cascade FRRs in series for decreasing power consumption and complexity of the system. • A universal strategy for multiplexing other cavity ring-down sensors. [ABSTRACT FROM AUTHOR]

The optical carrier-based microwave interferometry (OCMI) system for simultaneous loss and temperature measurement is proposed and demonstrated experimentally, which is implemented with the fiber loop ringdown (FLRD). By multiplexing the phase spectra of low and high radio frequencies (RF), the independent sensing of loss and temperature is achieved. With the advantages of robustness and immunity to crosstalk, the sensitivity of transmittance and temperature are at −0.4942 rad and −14.05 kHz/ ° C. The stability and tunable sensitivity of the sensing system are investigated and demonstrated by the numerical analysis and experiments. The principle of phase-shift FLRD is ameliorated by numerical investigation, verified by the experiment results. The independent sensing of loss and temperature is achieved by recording the phase spectra of low and high radio frequencies (RF), where the insensitive points play a vital role and provide a potential approach for multiplexing. • The OCMI system is proposed for simultaneous loss and temperature measurement. • The sensitivities of loss and temperature are flexibly tuned by selecting RF. • The sensitivity of transmittance and temperature are at −0.4942 rad and −14.05 kHz/℃. • The insensitive points provide a potential approach for multiplexing. [ABSTRACT FROM AUTHOR]

Cold-inducible RNA-binding protein (CIRBP) responds to a wide array of cellular stresses such as cold shock, hypoxia, and inflammatory responses. However, functional studies of CIRBP in jawless vertebrates are limited. In this study, a CIRBP homolog from the jawless vertebrate lamprey (Lethenteron reissneri) was cloned and characterized (named Lr-CIRBP). The cDNA fragment of Lr-CIRBP has a 516 bp open reading frame (ORF) that encodes 171 amino acids, comprising a glycine-rich region at the C-terminal, similar to higher vertebrates but slightly shorter, and an RNA recognition motif (RRM) domain at the N-terminus. The predicted Lr-CIRBP sequence had 51.4 ~ 70.6% similarity with CIRBPs from other vertebrates. Further phylogenetic analysis revealed that Lr-CIRBP is located in the outgroup of vertebrates and is the ancestor of vertebrates. Based on real-time quantitative PCR experimental analysis, Lr-CIRBP expression was highest in leukocytes and increased significantly after multi-stimulation, peaking at 12 h. RNA interference showed that Lr-CIRBP knockdown can down-regulate the expression of inflammatory factors in Lethenteron reissneri. In conclusion, our study successfully clarifies the ancestral features and functions of CIRBP, while revealing valuable insight into how the protein is involved in the immune responses of a jawless vertebrate. [ABSTRACT FROM AUTHOR]

• The proposed method improves the performance of FOCSs for fast dynamic measurements. • The impact of the noise on the measurement can be largely reduced. • The demodulation accuracy and robustness are experimentally investigated. It has been challenging to demodulate short-time and weak current signals collected by fiber optic current sensors (FOCSs) under ultra-high voltage, since the background noise can significantly affect the spectra of the current signals. To address this issue, here we propose a novel FOCS demodulation method based on backpropagation neural network, where the impact of the noise on the measurement can be largely reduced. The demodulation method can determine the amplitudes of short time series of weak currents with high resolution and accuracy. To evaluate the performance of the proposed method, the demodulation accuracy and robustness of the method are experimentally investigated and compared with those of the traditional fast Fourier transform (FFT) method. The experimental results show that our method can produce reliable results when demodulating weak current signals over short time windows of less than one period, and achieve a significantly lower standard deviation (6.7 mA) compared with the FFT method (15.6 mA) in the current range 0–0.306 A. The higher robustness against the background noise than the FFT method and the excellent repeatability of our demodulation method are also demonstrated through simulations. These results suggest that the proposed method will provide an effective way to improve the detection performances of FOCSs in fast dynamic measurements. [ABSTRACT FROM AUTHOR]

Purpose. Typical genes for the treatment and diagnosis of high-grade chondrosarcoma are still in need. Our study aimed to explore the PLCD1 function in chondrosarcoma for further treatment. Materials and Methods. Our study collected the information of 49 patients in our department. The PLCD1 expression in our cohort was detected and was compared with the TCGA database. PLCD1 knockdown and overexpression cell lines were established stably. Cell viability assay and colony formation assay were performed for cell proliferation. Flow cytometry analysis was performed for cell cycle and apoptosis. Western blotting was performed for PLCD1-related protein expression. Animal xenografts were established to verify the effect of PLCD1 in high-grade chondrosarcoma. Results. Compared with the TCGA database, the relation between PLCD1 expression and the malignancy of chondrosarcoma was demonstrated. A lower PLCD1 expression was detected mainly in high-grade chondrosarcoma. PLCD1 overexpression in high-grade chondrosarcoma suppressed CDKs/cyclins and induced DNA damage causing cell cycle blocking and apoptosis. Antitumor effect of PLCD1 overexpression was verified in vivo. Conclusion. Lower PLCD1 was expressed in high-grade chondrosarcoma. Overexpressed PLCD1-induced DNA damage caused cell cycle blocking and apoptosis in vitro and in vivo. PLCD1 could be a novel target in high-grade chondrosarcoma for further drug development. [ABSTRACT FROM AUTHOR]

Mathematics is a core content area in the science, technology, engineering, and mathematics (STEM) fields and is vital to student learning in the other STEM subjects. The purpose of this study was to investigate the math performance of fifth- and eighth-grade students in 1170 Texas school districts. We conducted growth hierarchical linear modeling in SAS 9.4 in order to explore the effects of time, district-level characteristics, and their interaction on student performance as measured by the State of Texas Assessments of Academic Readiness (STAAR) math test across three performance levels (i.e., approaching, meeting, and mastering grade level) over three academic years: 2016–2019. The overall findings indicated that, over time, Texas school districts improved in the percentage of students who approached, met, and mastered grade-level performance on the STAAR math test. The results also indicated that five district-level variables consistently and significantly impacted Grade 5 and 8 students' math achievement at three performance levels. Significant positive factors included the percentage of English learner students and principal years of experience; significant negative factors were the percentage of economically challenged students, student mobility rate, and teacher turnover rate. [ABSTRACT FROM AUTHOR]

A fiber optic current sensor (FOCS) demodulation algorithm based on differential-self-multiplication (DSM) is proposed, which is insensitive to the variation in phase modulation depth. It is theoretically analyzed and experimentally verified, compared with two traditional demodulation algorithms in this paper. DSM algorithm reduces demodulation errors caused by phase modulation depth variation that will cause harmonic amplitudes to approach zero. And the variation in phase modulation depth can be simulated by changing modulation voltage. In experiments, where the modulation frequency is 350 kHz and the modulation voltage ranges from 0.5 to 9 V, demodulation currents with DSM algorithms are not only more accurate but also more stable than traditional demodulation algorithms. In addition, the robustness of the DSM algorithm is demonstrated by repeating the experiment at different modulation frequency ranges from 100 to 600 kHz. This work provides a stable demodulation algorithm for FOCS, which can be extended to the applications in demodulation for other phase interferometers. • An algorithm that is insensitive to variation in phase modulation depth is proposed. • The proposed algorithm is compared with two traditional demodulation algorithms. • Repeated experiments at different modulation frequencies to demonstrate robustness. [ABSTRACT FROM AUTHOR]

This study compares the science achievement growth trajectories of fifth-grade students in rural and nonrural school districts in Texas. Using a growth hierarchical linear model, we explored the effects of time, school location (rural vs. nonrural), and their interaction on students' science performance as measured by the high-stakes State of Texas Assessment of Academic Readiness (STAAR) science test over five academic years. We found that rural school students lagged in science at the initial stage when STAAR was first administered in the 2011–2012 school year. With time, the gap between rural and nonrural district students' science performance persisted. We further added eight district-level factors that might influence students' academic performance into the model and found that three variables (i.e., student mobility rate, percentage of students identified ELs, and teacher turnover rate) constantly influenced students' science scores. The implications for teaching pedagogy and research are discussed regarding science education in Texas rural districts. [ABSTRACT FROM AUTHOR]

Osteosarcoma (OS) is ranked as the most common primary bone malignancy in children and adolescents worldwide, and the 5-year overall survival rate of OS is not optimistic. Constitutive activation of signal transducer and activator of transcription 3 (STAT3) has been implicated in tumor cell growth, proliferation, and anti-apoptosis in OS. Therefore, the discovery of novel molecular compounds that can effectively block STAT3 activation, is essential for the treatment of OS and improving prognosis. Here, we investigate whether Glaucocalyxin A (GLA), derived from Rabdosia japonica , exhibit the potential anticancer effects in OS. First of all, we identify that GLA potently suppressed cell proliferation, induced G2/M phase arrest and promoted substantial apoptosis in OS. Next, we conclude that GLA could induce Reactive oxygen species (ROS)-mediated oxidative stress via an imbalance of GSH and GSSG. Then, we elucidate for the first time that GLA could significantly inhibit both constitutive and IL-6-inducible activation of STAT3 (Tyr705) and JAK2, the upstream regulator of STAT3. Furthermore, we elucidate that the inhibition of STAT3 is mainly induced by ROS-mediated oxidative stress. Overall, our findings demonstrate that GLA could exhibit potent anticancer effects through effectively blocking the STAT3 signaling pathway, which was induced by ROS-mediated oxidative stress in OS in vitro and in vivo. Unlabelled Image • Glaucocalyxin A effectively blocks STAT3 signaling pathway through ROS-mediated oxidative stress due to an imbalance of GSSG/GSH in osteosarcoma cells. • Glaucocalyxin A induces GR activity via downregulating the mRNA and protein level of GR in vitro. [ABSTRACT FROM AUTHOR]

Background: Tumor angiogenesis, immunosuppression, and progression are all closely correlated with the tumor microenvironment (TME). Immune evasion is supported by both M2 phenotype tumor-associated macrophages (TAMs) and vascular aberrations in the TME. TME reprogramming is a promising therapeutic approach for treating tumors. Anti-angiogenesis has the power to control the polarization of macrophages, prevent progression, and increase drug penetration. Additionally, polyamine blocking therapy can increase CD8+ T cell infiltration and decrease immunosuppressive cells. These results led to developing a potential therapeutic regimen that targets TAMs and angiogenesis to reprogram the osteosarcoma TME. Results: For the targeted biomimetic co-delivery of regorafenib and alpha-difluoromethylornithine via the mannose receptor, which is overexpressed in both TAMs and osteosarcoma cells, mannosylated poly(lactide-co-glycolide)-polyethylene glycol nanoparticles (Man-NPs) were synthesized. The superior physiological properties and intratumoral accumulation of the Man-NPs efficiently promoted TAMs polarization and inhibited angiogenesis. Macrophage repolarization further activated immune cells, which contributed to remodeling the TME. Conclusion: Overall, these findings suggested that using Man-NPs as an immunotherapeutic approach to treat osteosarcoma may be promising. [ABSTRACT FROM AUTHOR]

• Microwave photonic interrogation for quasi-distributed FBG system is proposed. • Realize fast wavelength demodulation and location for cascaded FBGs simultaneously. • Coherent wavelength-to-time mapping is used to realize high measurement speed. • High resolution is obtained by pseudo-random barcode from fiber random grating. • Strain sensing resolution of 2.05 με with repetition rate of 20 MHz is achieved. A microwave photonic demodulation scheme for multiplexing fiber Bragg grating (FBG) sensing system based on coherent wavelength-to-time (WTT) mapping is proposed and demonstrated experimentally in this paper. With the help of mode-locked laser (MLL) source and dispersion element, the broadband pseudo-random barcode obtained from fiber random grating can be mapped into time domain to fulfill high-speed interrogation for FBGs. The shifts of FBG center wavelength will be transformed into the variations of filtered pseudo-random barcode, and finally converted into the time location changes of the cross-correlation peaks with narrow full-width half-maximum (FWHM), which is helpful to realize high-accuracy and high-resolution FBG demodulation utilizing oscilloscope. The experiment results exhibit good demodulation linearity and a strain interrogation sensitivity of 0.0302 ns/με in cascaded sensing network with a repetition rate of 20 MHz, corresponding to a strain measurement resolution of 2.05 με. Besides, the impacts of system noises and light source line-shapes on the demodulation performance are studied numerically, and the relevant solutions are proposed and verified respectively. [ABSTRACT FROM AUTHOR]

Osteosarcoma is the most common primary bone tumor, with a poor prognosis owing to the lack of efficient molecular-based targeted therapies. Previous studies have suggested an association between CD151 and distinct consequences in osteosarcoma tumorigenicity. However, the potential of CD151 as a therapeutic target has not yet been sufficiently explored. Here, we performed integrated transcriptomic and metabolomic analyses of osteosarcoma and identified sphingolipid metabolism as the top CD151-regulated pathway. CD151 regulates sphingolipid metabolism primarily through SPTCL1, the first rate-limiting enzyme in sphingolipid biosynthesis. Mechanistically, depletion of CD151 enhanced c-myc polyubiquitination and subsequent degradation. c-myc is vital for the transcriptional activation of SPTLC1. Functionally, sphingolipid synthesis and the SPTLC1 inhibitor, myriocin, significantly suppressed the clonogenic growth of CD151-overexpression cells. Importantly, myriocin selectively restrained CD151-high expression tumor growth in preclinical patient-derived xenograft models. Collectively, these data establish that CD151 is a key mediator of sphingolipid metabolism and provide a new approach to developing novel CD151-based targeted therapies for osteosarcoma. [ABSTRACT FROM AUTHOR]

Objective: To retrospectively analyze and compare the relationship between the success rate of patient‐derived xenograft (PDX) modeling of osteosarcoma and prognosis (3‐year overall survival rate and disease‐free survival rate) and incidence of lung metastasis. Methods: The sample group consisted of 57 osteosarcoma patients with definite pathological diagnoses from Shanghai General Hospital from 2015–2017. PDX models in 57 patients were analyzed by retrospective analyses. Among the patients currently inoculated, 20 were tumorigenic in the PDX model, and 37 were nontumorigenic. According to the tumorigenicity of PDXs, the corresponding osteosarcoma patients were divided into two groups. The effects of clinically related indicators on the model were retrospectively compared. The patients were followed, and the 3‐year survival, 3‐year disease‐free survival (DFS), and lung metastasis rates were collected. The relationship between the modeling success and patient prognosis was investigated. Results: In the chemotherapy‐treated group, the PDX modeling success rate was 17.4%, and in the nonchemotherapy group, the success rate was 47.1%. The success of PDX modeling was related to whether patients received chemotherapy. The success rate of PDX modeling is significantly reduced after receiving chemotherapy. The 3‐year overall survival rate of the PDX‐grafted group was 49.23%, and that of the PDX‐nongrafted group was 65.71%. There was a significant difference between the two groups, showing a strong negative correlation between the 3‐year survival rate and the success rate of the PDX model. The 3‐year disease‐free survival rate of the PDX‐grafted group was 29.54%. The 3‐year DFS of the PDX‐nongrafted group was 50.34%. There was a significant difference between the two groups. Lower grafted rates indicate a higher DFS rate. The incidence of lung metastasis in the PDX‐grafted group was 32.4%, and that in the nongrafted group was 13.1%. There was a significant difference between the two groups. The successful establishment of the PDX model indicates that patients are more likely to have lung metastases. Conclusions: The success of PDX modeling often indicates poor prognosis (low 3‐year overall survival rate and disease‐free survival rate) and a greater possibility of lung metastasis. Therefore, PDX modeling in osteosarcoma patients can accurately predict the prognosis of patients and the risk of lung metastasis in advance to help us develop better therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background: Osteosarcoma is the most common primary malignant bone tumor in children and adolescents and is characterized by frequent metastasis and resistance to chemotherapy. Because osteosarcoma cells are not highly susceptible to current chemotherapy drugs, new alternative strategies for the treatment of osteosarcoma are needed. This study was undertaken to investigate the inhibitory effects of a new synthetic ursolic acid derivative IUA on osteosarcoma cells and to explore its molecular mechanism. We also intended to identify new therapeutic candidates. Methods: We used MTT assay to assess the effect of IUA on the proliferation of osteosarcoma cells. Western-blot analysis was performed to examine downstream molecular events. The Annexin V method was used to evaluate the effect of IUA on apoptosis of osteosarcoma cells. The cell cycle of IUA-treated cells was examined by flow cytometry, and the in vivo effects of this new ursolic acid derivative were evaluated in a mouse osteosarcoma model. Results: The results showed that the new synthetic ursolic acid derivative IUA significantly decreased viability of osteosarcoma cells in vitro and in vivo. It could also induce apoptosis and G1 phase arrest of osteosarcoma cells. The JNK signaling pathway was significantly inhibited, and cleaved caspase-3 protein was increased. Conclusion: We concluded that the new synthetic ursolic acid derivative IUA induces proliferation inhibition and apoptosis of osteosarcoma cells in vitro and in vivo via the down-regulation of the JNK signaling pathway, making it a promising agent for the prevention and treatment of human osteosarcoma. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Papillary thyroid carcinoma (PTC) is a rare malignancy in children and young adults (CAYA). It often presents with aggressive disease patterns and advanced stages, which are clinically distinct from those in adult patients. In this study, we sought to characterize and better understand the clinical variants of PTC in CAYA and explore the underlying mechanisms. Methods: CAYA patients (age ≤18 years) diagnosed with PTC between June 2006 and June 2018 were retrospectively recruited from five hospitals. Demographic information, pathological data, and follow-up status were recorded. Tumor samples obtained from 20 children (mean age 15.15 years) and 10 adults (mean age 38.80 years) underwent comprehensive whole transcriptome sequencing. Differentially expressed genes (DEGs), mutational landscape, and immune infiltration were analyzed. Results: A total of 217 CAYA-PTC patients (162 females and 55 males) with an average age of 14.38 ± 3.53 years (range 2–18) were included. Lymph node metastasis (LNM) was observed in 85.71%, of which 57.60% were in the lateral cervical compartment. Disease recurred in 28 of 217 (12.90%) patients with a median follow-up of 4.76 years. Multivariate logistic regression analysis revealed that age, bilateral disease, extrathyroidal extension, and coexisting Hashimoto's thyroiditis (co-HT) were independent risk factors for LNM, while co-HT was the only risk factor for recurrence. Using whole transcriptome sequencing of PTC tissues, we identified 301 DEGs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses showed that differences in immune mediators played important roles, based on the distributions of mutation frequencies, types, and expression levels between CAYA and adult patients. Based on the integrated data sets, we identified significantly mutated immune genes, cluster of differentiation 24 (CD24), coagulation factor 12 (F12), coagulation factor 5 (F5), integrin subunit alpha 3 (ITGA3), and retinoic acid early transcript 1L (RAET1L), which were then verified by immunohistochemistry. Furthermore, resting mast cells, resting natural killer cells, plasma cells, and regulatory T cells were different in the CAYA-PTC group and correlated with the expression of immune checkpoints. Conclusions: There are considerable variabilities that may contribute to the different clinical presentations between CAYA and adult PTC patients, among which the decrease in protective immune cells may be a factor. Collectively, our results add to the possible biological mechanisms involved in CAYA-PTC. [ABSTRACT FROM AUTHOR]

• Osteosarcoma (OS) could be divided into two subtypes based on immune-related gene sets. • High immune cell infiltration subtype of OS predicted better prognosis. • Significant differences in immune cell infiltration were shown between two OS subtypes. • Verifying a new immune-related gene prognostic signature based on differentially expressed genes between two OS subtypes. Osteosarcoma (OS) is a highly aggressive cancer with poor prognosis, which mainly occurs in teenagers. Recent studies have shown that tumor-infiltrating immune cells play an important role in the progression of OS. In the present study, we identified two immune subtypes of OS (referred to as high and low immune cell infiltration subtypes, respectively) based on immune-related gene sets using TARGET and GEO cohort datasets. Elevated immune scores, increased stromal scores, decreased tumor purities, and higher infiltration of CD8 + T cells and M1 macrophages were observed for the high immune cell infiltration subtype. Moreover, the high immune cell infiltration subtype was characterized by high expression of immune checkpoint molecules. Gene set enrichment analysis showed that "B cell receptor signaling pathway" and "T cell receptor signaling pathway" gene sets were enriched in the high immune cell infiltration subtype. In addition, patients in the high immune cell infiltration subtype had better prognosis than patients in the low immune cell infiltration subtype. Furthermore, differentially expressed genes were screened according to the two OS subtypes and a risk model was generated by multivariate Cox regression analysis to predict the prognosis of OS patients. These results in this study showed that OS patients could be divided into two immune subtypes and offered a novel two-gene risk signature to predict the prognosis of patients with OS. [ABSTRACT FROM AUTHOR]

Background: Osteosarcoma (OS) is the most common primary bone cancer in adolescents and lung metastasis is the leading cause of death in patients with OS. However, the molecular mechanisms that promote OS growth and metastasis remain unknown. Methods: We investigated the expression of myosin light chain kinase family members between metastasis and non-metastasis patients in the TARGET database and ensured that only myosin light chain kinase family member 4 (MYLK4) had higher expression in metastatic osteosarcoma patients. Then we confirmed the results by immunohistochemistry (IHC) and Western blotting (WB) of OS tissues. The effect of MYLK4 on the metastasis and proliferation of OS cells was investigated by wound healing, Transwell and colony-formation assays. Mass spectrum analysis was used to ensure the new binding protein of MYLK4. Tissue microarrays analysis was used to show the correlation between MYLK4 and pEGFR (Y1068). A series of in vivo experiments were conducted to reveal the mechanisms by which MYLK4 modulated the metastasis and proliferation of OS. Results: Myosin Light Chain Kinase Family Member 4 (MYLK4) was significantly upregulated in metastatic human OS tissues. Growth and metastasis of OS could be accelerated by MYLK4 overexpression, whereas silencing MYLK4 expression resulted in decreased cell growth and metastasis. Mechanistically, mass spectrum analysis showed that MYLK4 interacted with the epidermal growth factor receptor (EGFR) in osteosarcoma cells and promoted growth and metastasis via the EGFR signaling pathway. Tissue microarrays analysis also showed that MYLK4 expression had a positive correlation with the expression of pEGFR (Y1068). Moreover, the EGFR inhibitor gefitinib could partially reverse the effect of cell proliferation and metastasis caused by MYLK4 overexpression. Importantly, the combination of MYLK4 and EGFR inhibitors had synergistic effects on growth and metastasis of OS in vitro and in vivo. Conclusion: Our results indicate that MYLK4 promotes OS growth and metastasis by activating the EGFR signaling pathway and can be a novel therapeutic target for the treatment of OS patients. [ABSTRACT FROM AUTHOR]

Despite the growing recognition of metabolic reprogramming as an important hallmark of cancer in the past few years, the molecular mechanisms underlying metabolic alterations during tumorigenesis remain unclear. In this study, we identified a critical role of Her4 in rewiring cancer metabolism toward tumor-promoting metabolic processes, including increased glycolysis, glutaminolysis, mitochondrial biogenesis, and oxidative phosphorylation, which may in part cooperate to promote tumorigenesis. We found that overexpression of Her4 promoted the stabilization of c-Myc through a CIP2A-mediated increase in c-MycS62 phosphorylation and GSK3β-mediated decrease in c-MycT58 phosphorylation, both of which decreased c-Myc degradation. Furthermore, Her4 was found to increase glucose uptake and tumor growth in an osteosarcoma xenograft model. Overall, these findings provide a better understanding of the involvement of Her4 in tumorigenesis and document its potential role in metabolic reprogramming for the first time. We believe that our study might lead to promising opportunities for targeted metabolic therapy for cancer. [ABSTRACT FROM AUTHOR]

Purpose: CXCR5-positive (CXCR5+) tumor cell infiltration has different prognostic values in different types of cancer. The objective was to evaluate the effect of CXCR5+ cell infiltration in head and neck squamous cell carcinoma (HNSCC). Patients and Methods: The study included two patient cohorts: The Cancer Genome Atlas cohort (TCGA, n = 472) and the Renji Hospital cohort (RJHC, n = 201). The TCGA and RJHC cohorts were analyzed for CXCR5-related mRNAs and CXCR5+ cell infiltration, respectively. We then evaluated the correlation between CXCR5 mRNA and CXCR5+ cell infiltration in terms of overall survival and the immune contexture. Results: The 5-year overall survival rate was significantly correlated with high CXCR5 mRNA expression and CXCR5+ cell infiltration in the TCGA and RJHC cohorts, respectively (p < 0.01), even after adjusting for confounders. Moreover, high CXCR5 mRNA expression was associated with more CD4+ T cells, CD8+ T cells, plasma cells, and less dendritic cells. A high CXCR5 mRNA expression was also correlated with increased expression of cytotoxic IFNG, TNFSF11 (RANKL), GZMA, GZMB, GZMK, GZMM, and PRF1 and increased expression of the immunosuppressive gene PDCD1 (PD-1), CD274 (PD-L1), CTLA4, LAG3, HAVCR2 (TIM-3), BTLA, and TIGIT. Conclusion: HNSCC patients with a high intratumoral CXCR5 expression had a better prognosis than those with low intratumoral CXCR5 expression. Moreover, CXCR5+ cell infiltration could be used as an independent prognostic biomarker or as a potential therapeutic target. The presence of CXCR5+ cells affects the infiltration of immunocytes in head and neck cancer, differently from what was reported in other cancer types. Further randomized controlled trials or studies with more patients are needed to validate our results. [ABSTRACT FROM AUTHOR]

Polycationic chitosan has a strong coordination to heavy metal ions due to its multifunctional hydroxyl and amino groups. However, due to the fast and facile dissolution of chitosan in acidic medium, it is difficult to measure the exact adsorption amount or coordination capacity accurately. In this work, a simple method of lyophilization plus ethanol-washing was employed to separate and purify chitosan/Cr(III) complex for further determining the coordination capacity. Meanwhile, the coordination structure of Bridge-chitosan-N(OH) 3 (H 2 O) and morphology of regenerated fibrillar sponge of CS/Cr(III) were further certified. The coordination capacity of Cr(III) on chitosan increased with the rising concentration of Cr(III) ions till the maximum coordination capacity was reached up to 355.03 mg/g. The mechanisms and characteristic parameters of the adsorption process were fit using two-parameter isotherm models which revealed the following order (based on the coefficient of determination) of Langmuir > Halsey > Freundlich > Temkin > Dubinin–Radushkevich. A proposed coordination formula of CS/Cr (III) might be a good certificate for the homogeneous chemical combination nature of Cr(III) on the monolayer surface of chitosan in a molecular scale. Unlabelled Image • A simple method of lyophilization plus ethanol-washing was employed to separate and purify chitosan/Cr(III) complex. • Maximum coordination capacity of Cr(III) ions on chitosan was high up to 355.03 mg/g. • A coordination structure of Bridge-chitosan-N(OH) 3 (H 2 O) was proposed. • Isotherm models suggest a homogeneous chemical combination on the monolayer. [ABSTRACT FROM AUTHOR]

Objective: Controversy still exists regarding the volume of radiation for head and neck cancer of unknown primary (HNCUP). Theoretically, elective mucosal irradiation (EMI) should achieve a balance between survival and toxicity. This prospective study was conducted to evaluate the long‐term benefit of EMI in Chinese HNCUP patients. Methods: A phase II, single‐arm trial was performed at two centers in China. HNCUP patients with pathologically confirmed metastatic squamous cell carcinoma or poorly differentiated carcinoma were enrolled. Patients with metastatic lymph nodes limited to level IV and/or the supraclavicular fossa were excluded. The EMI approach was specifically customized to Chinese patients by differentiating HNCUP as putative nasopharyngeal carcinoma (NPC) or non‐putative NPC. The primary endpoint was 3‐year mucosal recurrence‐free survival (MRFS). Results: A total of 48 patients were enrolled between 02/02/2010 and 08/01/2018; 46 patients were analyzed, including 24 putative NPC and 22 non‐putative NPC patients. No primary recurrence was observed during a median follow‐up period of 70 months, and only 1 patient experienced out of field recurrence in the contralateral neck. The 3‐year MRFS was 90.6% (95%CI: 76.4%‐96.4%). The 5‐year MRFS, regional‐recurrence free survival (RRFS) and overall survival (OS) were 90.6% (95%CI: 76.4%‐96.4%), 86.0% (95%CI: 71.1%‐93.7%), and 90.6% (95%CI: 76.4%‐96.4%), respectively. No grade 4 acute or late toxicities occurred, and the most frequent grade 3 acute toxicity was oral mucositis (45.7%). Conclusion: To the best of our knowledge, this is the first prospective study to evaluate the long‐term outcomes of EMI in Chinese HNCUP patients. Excellent MRFS and OS rates were observed. Further randomized studies are warranted. [ABSTRACT FROM AUTHOR]

Long noncoding RNAs (lncRNAs) are known to be key regulators of numerous biological processes, and substantial evidence supports that abnormal lncRNA expression plays a significant role in tumorigenesis and tumor progression. However, the mechanism by which lncRNAs function in thyroid carcinoma are still unclear. To investigate the role of lncRNAs in the tumorigenesis of papillary thyroid carcinoma (PTC), we analyzed lncRNA data in The Cancer Genome Atlas RNA‐Seq database. A comparison of lncRNAs in cancerous thyroid tissues and normal tissues revealed hundreds of differentially expressed lncRNAs. Of 7589 lncRNAs identified in 561 thyroid cancer cases (503 cancerous tissues and 58 normal tissues), the expression levels of 144 were found to be aberrant (|log2 fold change| >2 and adjusted P < 0.05). The top 10 lncRNAs with the most significant differences were LINC01977, RP11‐363E7.4, RP3‐483K16.4, RP11‐547D24.1, RUNDC3A‐AS1, AC093609.1, CTD‐2008L17.2, HAGLROS, UNC5B‐AS1, and LINC01354. In addition, CTD‐2008L17.2, HAGLROS, AC093609.1, UNC5B‐AS1, and RUNDC3A‐AS1 were shown to play vital roles in determining the histological cancer type. Furthermore, RP11‐547D24.1 and UNC5B‐AS1 could distinguish patients with different stages of PTC. The lncRNA RP11‐547D24.1 was validated by loss‐of‐function assays, revealing that downregulation of this lncRNA regulates thyroid tumor cell proliferation and apoptosis, invasion, and migration. This study demonstrates the potential for using lncRNAs to interpret the pathogenesis and development of PTC. [ABSTRACT FROM AUTHOR]

Osteosarcoma (OS) is the most common primary malignant bone tumor in children and adolescents. The abilities of chemotherapy resistance are major roadblock in the successful treatment of OS. The clarification of mechanism regarding cell survival during OS chemotherapy are important. Here, we examined HER4 expression by immunohistochemistry in a large series of OS tissues, and found HER4 expression correlated with tumor characteristics and patient survival rates. HER4 knockdown by shRNA inhibited OS cell growth and tumorigenesis, and induced cell senescence and apoptosis in vitro and in vivo. We demonstrated that HER4 expression upregulated in the adverse conditions, such as serum starvation and sphere culture. Moreover, HER4 knockdown cells became more sensitive in stressful conditions such as loss of attachment, cytotoxic agents or nutrition insufficiency. Mechanism studies revealed that HER4 interacted with NDRG1, and NDRG1 overexpression could antagonize HER4 knockdown-mediated cell growth and apoptosis in stressed conditions. There was a positive correlation between HER4 and NDRG1 immunoreactivity in OS patients. Together, our present study shows that HER4 and/or NDRG1 might play a critical role for the cell survival and chemo-resistance of OS, and could be used as potential therapeutic targets in OS. [ABSTRACT FROM AUTHOR]

Osteosarcoma is the most common primary bone malignancy in children and adolescents; it exhibits rapid growth and a high metastatic potential and may thus lead to relatively high mortality. The JAK2/STAT3 signaling pathway, which plays a critical role in the occurrence and development of osteosarcoma, is a potential target for the treatment of osteosarcoma. Here, we identified the natural product telocinobufagin (TCB), which is a component isolated from toad cake, as a potent candidate with anti-osteosarcoma effects. TCB inhibited osteosarcoma cell growth, migration, invasion and induced cancer cell apoptosis. Mechanistically, TCB specifically inhibited the JAK2/STAT3 signaling pathway. More importantly, TCB significantly suppressed tumor growth and metastasis in an osteosarcoma xenograft animal model. Moreover, TCB also showed strong inhibitory effects in other cancer types, such as lung cancer, liver cancer, colon cancer, breast cancer and gastric cancer. Hence, our study reveals TCB as a potent anti-osteosarcoma therapeutic agent that inhibits the JAK2/STAT3 signaling pathway. [Display omitted] • TCB suppresses the proliferation, migration and invasion of osteosarcoma cells. • TCB inhibits the growth and metastatsis of osteosarcoma via inhibiting JAK2/STAT3 signaling pathway. • TCB suppresses cell proliferation and invasion in other types of tumors. [ABSTRACT FROM AUTHOR]

Osteosarcoma is a common primary malignant bone tumor, the cure rate of which has stagnated over the past 25–30 years. Arsenic sulfide (As 2 S 2 ), the main active ingredient of the traditional Chinese medicine realgar, has been proved to have antitumor efficacy in several tumor types including acute promyelocytic leukemia, gastric cancer and colon cancer. Here, we investigated the efficacy and mechanism of As 2 S 2 in osteosarcoma both in vitro and in vivo . In this study, we demonstrated that As 2 S 2 potently suppressed cell proliferation by inducing G2/M phase arrest in various osteosarcoma cell lines. Also, treatment with As 2 S 2 induced apoptosis and autophagy in osteosarcoma cells. The apoptosis induction was related to PARP cleavage and activation of caspase-3, −8, −9. As 2 S 2 was demonstrated to induce autophagy as evidenced by formation of autophagosome and accumulation of LC3II. Further studies showed that As 2 S 2 -induced apoptosis and autophagy could be significantly attenuated by ROS scavenger and JNK inhibitor. Moreover, we found that As 2 S 2 inhibited Akt/mTOR signaling pathway, and suppressing Akt and mTOR kinases activity can increase As 2 S 2 -induced apoptosis and autophagy. Finally, As 2 S 2 in vivo suppressed tumor growth with few side effects. In summary, our results revealed that As 2 S 2 induced G2/M phase arrest, apoptosis, and autophagy via activing ROS/JNK and blocking Akt/mTOR signaling pathway in human osteosarcoma cells. Arsenic sulfide may be a potential clinical antitumor drugs targeting osteosarcoma. [ABSTRACT FROM AUTHOR]

Signal transducer and activator of transcription 3 (STAT3) plays essential roles in cancer progression and has been considered as a promising target for cancer therapy. Here, we used a dual luciferase assay to identify that pectolinarigenin inhibited STAT3 transcriptional activity. Further, results showed pectolinarigenin inhibited constitutive and IL6 induced STAT3 signaling, diminished the accumulation of STAT3 in the nucleus, dimerization and blocked STAT3 DNA binding activity. Mechanism investigations indicated that pectolinarigenin disturbed the STAT3/DNMT1/HDAC1 complex formation in the promoter region of SHP-1, which reversely mediates STAT3 signaling, leading to the upregulation of SHP-1 expression in osteosarcoma. We also found pectolinarigenin significantly suppressed osteosarcoma growth, induced apoptosis. In addition, pectolinarigenin blocked tumor cells migration, invasion and reserved EMT phenotype. In spontaneous tibial injection and patient-derived xenograft models of osteosarcoma, we identified administration (i.p.) of pectolinarigenin (20 mg/kg/2 days and 50 mg/kg/2 days) blocked STAT3 activation and disturbed tumor growth and metastasis with superior pharmacodynamic properties. Taken together, our findings demonstrate that pectolinarigenin may be a candidate for osteosarcoma intervention linked to its STAT3 signaling inhibitory activity. [Display omitted] • STAT3 pathway may represent a promising target for therapeutic intervention in osteosarcoma. • pectolinarigenin is a potent inhibitor of STAT3 signaling in osteosarcoma. • Pectolinarigenin inhibits osteosarcoma tumor growth and metastasis in vivo. • pectolinarigenin shows few side effects on mouse. [ABSTRACT FROM AUTHOR]

In this study, we evaluated the photodynamic efficacy of a new photosensitizer, benzochloroporphyrin derivative 18 (BCPD-18), in Ewing sarcoma. We found that BCPD-18 decreased the viability of TC-71 cells irradiated by 670 nm laser in a concentration dependent manner. We also observed cells undergoing apoptosis as well as cell cycle arrest at the G2M phase after BCPD–18-mediated photodynamic therapy (BCPD-PDT). In addition, in vivo study (subcutaneous and orthotopic models) showed that BCPD-PDT reduced tumor size, tumor weight and tumor-bearing leg weight. After PDT, apoptosis was shown in vivo. Bax expression was increased, and Bcl-2 expression was decreased. This study provides evidence that BCPD-18 could probably be a useful photosensitizer in PDT for Ewing sarcoma. [ABSTRACT FROM AUTHOR]

This study was carried out to investigate the anti-tumor effect and mechanism of hiporfin-mediated photodynamic therapy (hiporfin- PDT) in osteosarcoma. We found that hiporfin accumulated mainly in the cytoplasm of osteosarcoma cells in a time and concentration-dependent manner. Hiporfin- PDT inhibited the proliferation, induced apoptosis and produced cell cycle arrest at G2 M in osteosarcoma cell lines. Hiporfin- PDT increased the expression of cleaved-caspase-3, cleaved PARP-1, Bax and RIP1 while it decreased the expression of Bcl-2; in addition, low concentration of hiporfin increased LC3 conversion. Furthermore, cell death caused by hiporfin- PDT could be rescued by Nec-1 but not by Z- VAD- FMK. Production of reactive oxygen species was increased after hiporfin- PDT. In vivo studies showed a significant decrease in tumor volume and weight after hiporfin- PDT in all three tumor mouse models investigated (subcutaneous and orthotopic). Histological analysis showed widespread cell apoptosis and necrosis after treatment. Immunohistochemistry also showed upregulation of cleaved-caspase-3 and downregulation of Bcl-2 after hiporfin- PDT. These results indicate that hiporfin- PDT exhibits a killing effect in osteosarcoma both in vitro and in vivo, which is associated with apoptosis and necroptosis, while autophagy plays a protective role. All these findings shed light on a potential future clinical use for hiporfin in the treatment of osteosarcoma. [ABSTRACT FROM AUTHOR]

We investigated the antitumor effect and mechanism of hematoporphyrin monomethyl ether-mediated photodynamic therapy (HMME-PDT) in sarcomas. Intracellular uptake of HMME by osteosarcoma cells (LM8 and K7) was time- and dose-dependent, while this was not observed for myoblast cells (C2C12) and fibroblast cells (NIH/3T3). HMME-PDT markedly inhibited the proliferation of sarcoma cell lines (LM8, MG63, Saos-2, SW1353, TC71, and RD) (P<0.05), and the killing effect was improved with increased HMME concentration and energy intensity. Flow cytometry analysis revealed that LM8, MG63, and Saos-2 cells underwent apoptosis after treatment with HMME-PDT. Additionally, apoptosis was induced after HMME-PDT in a three-dimensional culture of osteosarcoma cells. Hoechst 33342 staining confirmed apoptosis. Cell death caused by PDT was rescued by an irreversible inhibitor (Z-VAD-FMK) of caspase. However, cell viability was not markedly decreased compared with the HMME-PDT group. Expression levels of caspase-1, caspase-3, caspase-6, caspase-9, and poly (ADP-ribose) polymerase (PARP) proteins were markedly up-regulated in the treatment groups and increased with HMME concentration as determined by western blot analysis. In vivo, tumor volume markedly decreased at 7–16 days post-PDT. Hematoxylin and eosin staining revealed widespread necrotic and infiltrative inflammatory cells in the HMME-PDT group. Immunohistochemistry analysis also showed that caspase-1, caspase-3, caspase-6, caspase-9, and PARP proteins were significantly increased in the HMME-PDT group. These results indicate that HMME-PDT has a potent killing effect on osteosarcoma cells in vitro and significantly inhibits tumor growth in vivo, which is associated with the caspase-dependent pathway. [ABSTRACT FROM AUTHOR]

Background: Osteosarcoma is the most frequent primary malignant bone tumor, notorious for its lung metastasis. Shikonin, an effective constituent extracted from Chinese medicinal herb, was demonstrated to induce necroptosis in some cancers.Methods: MTT assay was performed to detect cell survival rate in vitro. Flow cytometry was used to analyze cell cycle and cell death. Western blot was performed to determine the expression levels of RIP1, RIP3, caspase-3, caspase-6 and PARP. The tibial primary and lung metastatic osteosarcoma models were used to evaluate the anti-tumor effect of shikonin in vivo.Results: The cell survival rate was decreased in a dose and time dependent manner when treated with shikonin. No major change in cell cycle was observed after shikonin treatment. The cell death induced by shikonin could be mostly rescued by specific necroptosis inhibitor necrostatin-1, but not by general caspase inhibitor Z-VAD-FMK. The number of necrotic cells caused by shikonin was decreased after being pretreated with Nec-1 detected by flow cytometry in K7 cells. After 8-hour treatment of shikonin, the expression levels of RIP1 and RIP3 were increased while caspase-3, caspase-6 and PARP were not activated in K7 and U2OS cells determined by Western blot. Size of primary tumor and lung metastasis in shikonin treated group were significantly reduced. The protein levels of RIP1 and RIP3 in primary tumor tissues were increased by shikonin. The overall survival of lung metastatic models was longer compared with control group (p < 0.001).Conclusions: Shikonin had prompt but profound anti-tumor effect on both primary and metastatic osteosarcoma, probably by inducing RIP1 and RIP3 dependent necroptosis. Shikonin would be a potential anti-tumor agent on the treatment of primary and metastatic osteosarcoma. [ABSTRACT FROM AUTHOR]

In this study, we described and compared an English as a foreign language (EFL) teacher's pedagogical behaviors in traditional and problem-based learning (PBL) classroom settings in a Chinese university. In spring 2019, we collected six 45-min videos, three in each condition, covering three modules: (a) warm-up and vocabulary, (b) essay structure, and (c) writing. The analyses of the teacher's pedagogical behaviors and her interaction with students indicated that the instructor spent most of the instructional time delivering higher-order thinking content in both traditional and PBL classes. The teacher's activity structure influenced students' communication mode. Although the instructor provided students with more group discussion activities in the PBL classroom, lecturing was observed to be the primary delivery method in both classes. These results suggest that the application of PBL strategies in the EFL classroom did not significantly restructure the teacher's pedagogical behaviors, and thus, failed to achieve the goal of providing students with more opportunities for improving their expressive English language proficiency. These findings underscore the need to develop an effective PBL-related curriculum and professional development opportunities for EFL teachers to effectively implement the PBL approach in the classroom. [ABSTRACT FROM AUTHOR]

Fullerene C60 nanocrystals (nano‐C60) possess various attractive bioactivities, including autophagy induction and calcium/calmodulin‐dependent protein kinase IIα (CaMKIIα) activation. CaMKIIα is a multifunctional protein kinase involved in many cellular processes including tumor progression; however, the biological effects of CaMKIIα activity modulated by nano‐C60 in tumors have not been reported, and the relationship between CaMKIIα activity and autophagic degradation remains unclear. Herein, nano‐C60 is demonstrated to elicit reactive oxygen species (ROS)‐dependent cytotoxicity and persistent activation of CaMKIIα in osteosarcoma (OS) cells. CaMKIIα activation, in turn, produces a protective effect against cytotoxicity from nano‐C60 itself. Inhibition of CaMKIIα activity by either the chemical inhibitor KN‐93 or CaMKIIα knockdown dramatically promotes the anti‐OS effect of nano‐C60. Moreover, inhibition of CaMKIIα activity causes lysosomal alkalinization and enlargement, and impairs the degradation function of lysosomes, leading to autophagosome accumulation. Importantly, excessive autophagosome accumulation and autophagic degradation blocking are shown to play an important role in KN‐93‐enhanced‐OS cell death. The synergistic anti‐OS efficacy of KN‐93 and nano‐C60 is further revealed in an OS‐xenografted murine model. The results demonstrate that CaMKIIα inhibition, along with the suppression of autophagic degradation, presents a promising strategy for improving the antitumor efficacy of nano‐C60. [ABSTRACT FROM AUTHOR]

Background: Osteosarcoma (OS) is a common malignant cancer in children and adolescents and has a cure rate that has not improved in the last two decades. CYT997 (lexibulin) is a novel potent microtubule-targeting agent with various anticancer activities, such as proliferation inhibition, vascular disruption, and cell cycle arrest and apoptosis induction, in multiple cancers. However, the direct cytotoxic mechanisms of CYT997 have not yet been fully characterized. Methods: We evaluated apoptosis and autophagy in human osteosarcomas after treatment with CYT997 and investigated the underlying mechanisms. To explore relationships, we used the reactive oxygen species (ROS) scavenger N-acetyl cysteine (NAC), PERK inhibitor GSK2606414, ERO1 inhibitor EN460 and mitochondrial targeted protection peptide elamipretide. BALB/c-nu mice were inoculated with 143B tumor cells to investigate the in vivo effect of CYT997. Results: We explored the efficacy and mechanism of CYT997 in osteosarcoma (OS) in vitro and in vivo and demonstrated that CYT997 potently suppresses cell viability and induces apoptosis and autophagy. CYT997 triggered production of ROS and exerted lethal effects via endoplasmic reticulum (ER) stress in OS cells. NAC attenuated these effects. The PERK inhibitor GSK2606414, which can block the ER stress pathway, reduced ROS production and enhanced cell viability. Moreover, activation of ERO1 in the ER stress pathway was responsible for inducing ROS production. ROS produced by the mitochondrial pathway also aggravate ER stress. Protection of mitochondria can reduce apoptosis and autophagy. Finally, CYT997 prominently reduced tumor growth in vivo. Conclusions: This study suggests that CYT997 induces apoptosis and autophagy in OS cells by triggering mutually enhanced ER stress and ROS and may thus be a promising agent against OS. [ABSTRACT FROM AUTHOR]

Background: Anaplastic thyroid carcinoma (ATC) is a malignancy with one of the highest fatality rates. We reviewed our recent clinical experience with intensity modulated radiotherapy (IMRT) combined with surgery and chemotherapy for the management of ATC.Methods: 13 patients with ATC who were treated by IMRT in our institution between October 2008 and February 2011, have been analyzed. The target volume for IMRT was planned to include Gross tumor volume (GTV): primary tumor plus any N + disease (66 Gy/33 F/6.6 W), with elective irradiation of thyroid bed, bilateral level II through VI and mediastinal lymph nodes to the level of the carina (54-60 Gy). Seven patients received surgical intervention and eleven patients had chemotherapy.Results: The median radiotherapy dose to GTV was 60 Gy/30 fractions/6 weeks. The median survival time of the 13 patients was 9 months. The direct causes of death were distant metastases (75%) and progression of the locoregional disease (25%). Ten patients were spared dyspnea and tracheostomy because their primary neck lesion did not progress.Conclusion: The results showed that IMRT combined by surgery and chemotherapy for ATC might be beneficial to improve locoregional control. Further new therapies are needed to control metastases. [ABSTRACT FROM AUTHOR]