CT-derived Radiomics Predicts the Efficacy of Tyrosine Kinase Inhibitors in Osteosarcoma Patients with Pulmonary Metastasis.

BACKGROUND: To construct and validate the CT-based radiomics model for predicting the tyrosine kinase inhibitors (TKIs) effects in osteosarcoma (OS) patients with pulmonary metastasis. METHODS: OS patients with pulmonary metastasis treated with TKIs were randomly separated into training and testing cohorts (2:1 ratio). Radiomic features were extracted from the baseline unenhanced chest CT images. The random survival forest (RSF) and Kaplan-Meier survival analyses were performed to construct and evaluate radiomics signatures (R-model-derived). The univariant and multivariant Cox regression analyses were conducted to establish clinical (C-model) and combined models (RC-model). The discrimination abilities, goodness of fit and clinical benefits of the three models were assessed and validated in both training and testing cohorts. RESULTS: A total of 90 patients, 57 men and 33 women, with a mean age of 18 years and median progression-free survival (PFS) of 7.2 months, were enrolled. The R-model was developed with nine radiomic features and demonstrated significant predictive and prognostic values. In both training and testing cohorts, the time-dependent area under the receiver operating characteristic curves (AUC) of the R-model and RC-model exhibited obvious superiority over C-model. The calibration and decision curve analysis (DCA) curves indicated that the accuracy of the R-model was comparable to RC-model, which exhibited significantly better performance than C-model. CONCLUSIONS: The R-model showed promising potential as a predictor for TKI responses in OS patients with pulmonary metastasis. It can potentially identify pulmonary metastatic OS patients most likely to benefit from TKIs treatment and help guide optimized clinical decisions.

RNA aggregates harness the danger response for potent cancer immunotherapy.

Cancer immunotherapy remains limited by poor antigenicity and a regulatory tumor microenvironment (TME). Here, we create "onion-like" multi-lamellar RNA lipid particle aggregates (LPAs) to substantially enhance the payload packaging and immunogenicity of tumor mRNA antigens. Unlike current mRNA vaccine designs that rely on payload packaging into nanoparticle cores for Toll-like receptor engagement in immune cells, systemically administered RNA-LPAs activate RIG-I in stromal cells, eliciting massive cytokine/chemokine response and dendritic cell/lymphocyte trafficking that provokes cancer immunogenicity and mediates rejection of both early- and late-stage murine tumor models. In client-owned canines with terminal gliomas, RNA-LPAs improved survivorship and reprogrammed the TME, which became "hot" within days of a single infusion. In a first-in-human trial, RNA-LPAs elicited rapid cytokine/chemokine release, immune activation/trafficking, tissue-confirmed pseudoprogression, and glioma-specific immune responses in glioblastoma patients. These data support RNA-LPAs as a new technology that simultaneously reprograms the TME while eliciting rapid and enduring cancer immunotherapy.

The truncated AXIN1 isoform promotes hepatocellular carcinoma metastasis through SRSF9-mediated exon 9 skipping.

Axis inhibitor protein 1 (AXIN1) is a protein recognized for inhibiting tumor growth and is commonly involved in cancer development. In this study, we explored the potential molecular mechanisms that connect alternative splicing of AXIN1 to the metastasis of hepatocellular carcinoma (HCC). Transcriptome sequencing, RT‒PCR, qPCR and Western blotting were utilized to determine the expression levels of AXIN1 in human HCC tissues and HCC cells. The effects of the AXIN1 exon 9 alternative splice isoform and SRSF9 on the migration and invasion of HCC cells were assessed through wound healing and Transwell assays, respectively. The interaction between SRSF9 and AXIN1 was investigated using UV crosslink RNA immunoprecipitation, RNA pulldown, and RNA immunoprecipitation assays. Furthermore, the involvement of the AXIN1 isoform and SRSF9 in HCC metastasis was validated in a nude mouse model. AXIN1-L (exon 9 including) expression was downregulated, while AXIN1-S (exon 9 skipping) was upregulated in HCC. SRSF9 promotes the production of AXIN1-S by interacting with the sequence of exons 8 and 10 of AXIN1. AXIN1-S significantly promoted HCC cells migration and invasion by activating the Wnt pathway, while the opposite effects were observed for AXIN1-L. In vivo experiments demonstrated that AXIN1-L inhibited HCC metastasis, whereas SRSF9 promoted HCC metastasis in part by regulating the level of AXIN1-S. AXIN1, a tumor suppressor protein that targets the AXIN1/Wnt/ß-catenin signaling axis, may be a promising prognostic factor and a valuable therapeutic target for HCC.

Drought responses and carbon allocation strategies of poplar with different leaf maturity.

Leaf characteristics can reflect the adaptation of trees to drought stress. However, the effect of leaf maturity on drought stress has been neglected, leading to uncertainty in inferring individual tree responses to drought from leaves. The allocation strategy of photosynthetic carbon between leaf organs (fully expanded young and old leaves) under drought stress remains unclear. Poplar is a diverse and widespread tree species in arid and semi-arid regions. Here, three poplar genotypes (Populus cathayana, P. × euramericana 'Nanlin 895', and P. alba × P. tremula var. glandulosa) were selected and exposed to different watering regimes. The responses and carbon allocation strategies of leaves with different maturity to drought were investigated using a combination of leaf traits and 13 C pulse labelling technique. The results showed that (1) fully expanded young leaves had better osmotic regulation and antioxidant capacity than aged leaves under drought stress. (2) Aged leaves acted as a carbon source during water deficit, where their photosynthetic products were transferred and supplied to upper young leaves to promote stronger photosynthesis in young leaves to acquire resources for tree growth. This study highlights that the effect of leaf maturity should be considered in the future when investigating the effects of drought on woody plants, especially for continuously growing tree species. Therefore, our study not only demonstrates the existence of leaf-age-dependent responses to drought in poplar but also provides new insights into carbon allocation at the leaf level.

Expanded specific T cells to hypomutated regions of the SARS-CoV-2 using mRNA electroporated antigen-presenting cells.

The COVID-19 pandemic has caused about seven million deaths worldwide. Preventative vaccines have been developed including Spike gp mRNA-based vaccines that provide protection to immunocompetent patients. However, patients with primary immunodeficiencies, patients with cancer, or hematopoietic stem cell transplant recipients are not able to mount robust immune responses against current vaccine approaches. We propose to target structural SARS-CoV-2 antigens (i.e., Spike gp, Membrane, Nucleocapsid, and Envelope) using circulating human antigen-presenting cells electroporated with full length SARS-CoV-2 structural protein-encoding mRNAs to activate and expand specific T cells. Based on the Th1-type cytokine and cytolytic enzyme secretion upon antigen rechallenge, we were able to generate SARS-CoV-2 specific T cells in up to 70% of unexposed unvaccinated healthy donors (HDs) after 3 subsequent stimulations and in 100% of recovered patients (RPs) after 2 stimulations. By means of SARS-CoV-2 specific TCRß repertoire analysis, T cells specific to Spike gp-derived hypomutated regions were identified in HDs and RPs despite viral genomic evolution. Hence, we demonstrated that SARS-CoV-2 mRNA-loaded antigen-presenting cells are effective activating and expanding COVID19-specific T cells. This approach represents an alternative to patients who are not able to mount adaptive immune responses to current COVID-19 vaccines with potential protection across new variants that have conserved genetic regions.

Quantized anomalous Hall resistivity achieved in molecular beam epitaxy-grown MnBi2Te4 thin films.

The intrinsic magnetic topological insulator MnBi2Te4 provides a feasible pathway to the high-temperature quantum anomalous Hall (QAH) effect as well as various novel topological quantum phases. Although quantized transport properties have been observed in exfoliated MnBi2Te4 thin flakes, it remains a big challenge to achieve molecular beam epitaxy (MBE)-grown MnBi2Te4 thin films even close to the quantized regime. In this work, we report the realization of quantized anomalous Hall resistivity in MBE-grown MnBi2Te4 thin films with the chemical potential tuned by both controlled in situ oxygen exposure and top gating. We find that elongated post-annealing obviously elevates the temperature to achieve quantization of the Hall resistivity, but also increases the residual longitudinal resistivity, indicating a picture of high-quality QAH puddles weakly coupled by tunnel barriers. These results help to clarify the puzzles in previous experimental studies on MnBi2Te4 and to find a way out of the big difficulty in obtaining MnBi2Te4 samples showing quantized transport properties.

The efficacy and adverse events of arsenic trioxide for the patients with myelodysplastic syndrome: a systematic review and component network meta-analysis.

BACKGROUND: Arsenic trioxide (ATO) might be effective for myelodysplastic syndrome (MDS) by apoptosis induction and demethylation. But ATO has not been widely recommended for small sample and conflicting conclusion of existing trials. This review aimed to systematically evaluate the efficacy of regimens containing ATO for the MDS and explore optimal combination. METHOD: Randomized clinical trials (RCTs) about ATO regimens were retrieved from China National Knowledge Infrastructure, Embase and PubMed. With odds ratio (OR) as the effect size, network meta-analysis (NMA) and component network meta-analysis (CNMA) were conducted by R and 'netmeta' package, after study selection, quality assessment and data extraction. RESULT: Thirty-night RCTs were included with a total of 2125 patients, including 1235 treated by ATO containing regimen. With support therapy alone as reference, no inconsistency and heterogeneity were observed. Although NMA did not demonstrate better efficacy of ATO alone, the result of CNMA indicated that ATO was effective in the improvement of overall remission (ORR) [OR = 2.09(1.61, 2.71)] and complete remission (CR) [OR = 1.66(1.25, 2.21)]. Five ATO-containing regimens reported could effectively improve ORR, some of them benefit in CR or hematological improvement (HI) as well. ATO + Traditional Chinese Medicine (TCM), ATO + Thalidomide (T)+TCM, ATO + Chemotherapy (Chem)+T + TCM were regarded as the optimal combination, which improved both ORR, CR and HI in theory. ATO did not increase the risk of common adverse events compared to supportive therapy [(OR = 0.90(0.67, 1.21)]. CONCLUSION: ATO may be an effective and well-tolerant option for patients with myelodysplastic syndrome.

Bioconjugated liquid-like solid enhances characterization of solid tumor - chimeric antigen receptor T cell interactions.

Chimeric antigen receptor (CAR) T cell therapy has demonstrated remarkable success as an immunotherapy for hematological malignancies, and its potential for treating solid tumors is an active area of research. However, limited trafficking and mobility of T cells within the tumor microenvironment (TME) present challenges for CAR T cell therapy in solid tumors. To gain a better understanding of CAR T cell function in solid tumors, we subjected CD70-specific CAR T cells to a challenge by evaluating their immune trafficking and infiltration through a confined 3D microchannel network in a bio-conjugated liquid-like solid (LLS) medium. Our results demonstrated successful CAR T cell migration and anti-tumor activity against CD70-expressing glioblastoma and osteosarcoma tumors. Through comprehensive analysis of cytokines and chemokines, combined with in situ imaging, we elucidated that immune recruitment occurred via chemotaxis, and the effector-to-target ratio plays an important role in overall antitumor function. Furthermore, through single-cell collection and transcriptomic profiling, we identified differential gene expression among the immune subpopulations. Our findings provide valuable insights into the complex dynamics of CAR T cell function in solid tumors, informing future research and development in this promising cancer treatment approach. STATEMENT OF SIGNIFICANCE: The use of specialized immune cells named CAR T cells to combat cancers has demonstrated remarkable success against blood cancers. However, this success is not replicated in solid tumors, such as brain or bone cancers, mainly due to the physical barriers of these solid tumors. Currently, preclinical technologies do not allow for reliable evaluation of tumor-immune cell interactions. To better study these specialized CAR T cells, we have developed an innovative in vitro three-dimensional model that promises to dissect the interactions between tumors and CAR T cells at the single-cell level. Our findings provide valuable insights into the complex dynamics of CAR T cell function in solid tumors, informing future research and development in this promising cancer treatment approach.

Three-Dimensional Bioconjugated Liquid-Like Solid (LLS) Enhance Characterization of Solid Tumor - Chimeric Antigen Receptor T cell interactions.

Cancer immunotherapy offers lifesaving treatments for cancers, but the lack of reliable preclinical models that could enable the mechanistic studies of tumor-immune interactions hampers the identification of new therapeutic strategies. We hypothesized 3D confined microchannels, formed by interstitial space between bio-conjugated liquid-like solids (LLS), enable CAR T dynamic locomotion within an immunosuppressive TME to carry out anti-tumor function. Murine CD70-specific CAR T cells cocultured with the CD70-expressing glioblastoma and osteosarcoma demonstrated efficient trafficking, infiltration, and killing of cancer cells. The anti-tumor activity was clearly captured via longterm in situ imaging and supported by upregulation of cytokines and chemokines including IFNg, CXCL9, CXCL10, CCL2, CCL3, and CCL4. Interestingly, target cancer cells, upon an immune attack, initiated an "immune escape" response by frantically invading the surrounding microenvironment. This phenomenon however was not observed for the wild-type tumor samples which remained intact and produced no relevant cytokine response. Single cells collection and transcriptomic profiling of CAR T cells at regions of interest revealed feasibility of identifying differential gene expression amongst the immune subpopulations. Complimentary 3D in vitro platforms are necessary to uncover cancer immune biology mechanisms, as emphasized by the significant roles of the TME and its heterogeneity.

mRNA challenge predicts brain cancer immunogenicity and response to checkpoint inhibitors.

To prospectively determine whether brain tumors will respond to immune checkpoint inhibitors (ICIs), we developed a novel mRNA vaccine as a viral mimic to elucidate cytokine release from brain cancer cells in vitro. Our results indicate that cytokine signatures following mRNA challenge differ substantially from ICI responsive versus non-responsive murine tumors. These findings allow for creation of a diagnostic assay to quickly assess brain tumor immunogenicity, allowing for informed treatment with ICI or lack thereof in poorly immunogenic settings.

Protein arginine methyltransferase 8 regulates ferroptosis and macrophage polarization in spinal cord injury via glial cell-derived neurotrophic factor.

OBJECTIVE: To explore the influence of protein arginine methyltransferase 8 (PRMT8) regulating glial cell-derived neurotrophic factor (GDNF) on neuron ferroptosis and macrophage polarization in spinal cord injury (SCI). METHODS: A rat model of SCI was established through an injury induced by an external force. Basso, Beattie, and Bresnahan score, hematoxylin and eosin staining, and immunofluorescence were used, respectively, to detect changes in rat locomotion, spinal cord histopathology, and NeuN expression in the spinal cord. Iron content in the spinal cord and levels of malondialdehyde and glutathione were measured using detection kits. Transmission electron microscopy was used to reveal the morphological characteristics of mitochondria. Western blotting was performed to detect PRMT8, GDNF, cystine/glutamate transporter XCT, glutathione peroxidase 4, 4-hydroxynonenal, heme oxygenase-1, inducible nitric oxide synthase (iNOS), CD16, and arginase 1 (Arg1). The expression levels of iNOS and Arg1 in the spinal cord were visualized by immunofluorescence. ELISA was performed to measure the expression levels of IL-6, IL-1ß, and TNF-α. Rat dorsal root ganglion (DRG) neurons and RMa-bm rat macrophages were treated with lipopolysaccharide under hypoxic conditions. The viability and iron content of the neurons were detected using Cell Counting Kit-8 and a specific probe, respectively. Flow cytometry and immunofluorescence were used to assess macrophage polarization. Chromatin immunoprecipitation was used to identify the binding of PRMT8 to the GDFN promoter. RESULTS: Neuronal ferroptosis and M1 macrophage polarization were promoted, and PRMT8 expression was downregulated in SCI. PRMT8 overexpression exerted therapeutic effects on injured DRG neurons and RMa-bm cells. Moreover, PRMT8 overexpression inhibited ferroptosis and M1 macrophage polarization in rats with SCI. PRMT8 promoted GDNF expression by catalyzing H3K4 methylation. Knockdown of GDNF counteracted the therapeutic effects of PRMT8 overexpression. CONCLUSION: Overexpression of PRMT8 may inhibit ferroptosis and M1 macrophage polarization by increasing GDNF expression, thereby alleviating SCI.

Power Enhancement of 265 nm DUV-LED Flip-Chip by HVPE-AlN High-Temperature Annealing.

In this paper, the X-ray diffraction full width at half the maximum (XRD FWHM) of a 3.5 µm-thick hydride vapor phase epitaxy-aluminum nitride (HVPE-AlN) (002) face after high-temperature annealing was reduced to 129 arcsec. The tensile strain in the HVPE-AlN samples gradually released with the increasing annealing temperature. When the annealing temperature exceeded 1700 °C, an aluminum oxynitride (AlON) region was generated at the contact interface between HVPE-AlN and sapphire, and the AlON structure was observed to conform to the characteristics of Al5O6N by high-resolution transmission electron microscopy (HRTEM). A 265 nm light-emitting diode (LED) based on an HVPE-AlN template annealed at 1700 °C achieved a light output power (LOP) of 4.48 mW at 50 mA, which was approximately 57% greater than that of the original sample.

A 3D printed sandwich-type piezoelectric motor with a surface texture.

Polymer-based piezoelectric motors have excellent properties, such as lightweight and corrosion resistance. In addition, 3D printing and customized additive manufacturing of polymers provide new opportunities for the development of piezoelectric motors with complex or special structures. In this paper, a 3D printed polymer-based sandwich-type piezoelectric motor operating in a single longitudinal mode is developed. A vibration decomposition model of the motor and an analytical model considering polymer viscoelasticity are established to analyze the dynamic characteristics and to determine the geometric structure of the motor. To increase the coefficient of friction, a polymer surface texture is utilized on the contacts. The experimental results show that the friction coefficient of the contact tip with surface texture is about 0.16, which increased by 45.5% compared to a smooth surface. The resonance frequency is 28.648 kHz, and the maximum no-load speed under 300 Vp-p is 54 r/min. Our study shows the promise of polymer-based materials in the development of the piezoelectric motor.

Self-Assembling Imageable Silk Hydrogels for the Focal Treatment of Osteosarcoma.

Background: The standard treatment for osteosarcoma comprises complete surgical resection and neoadjuvant chemotherapy, which may cause serious side effects and partial or total limb loss. Therefore, to avoid the disadvantages of traditional treatment, we developed self-assembling imageable silk hydrogels for osteosarcoma. Methods: We analysed whether iodine induced apoptosis in MG-63 and Saos-2 cells by using CCK-8 and flow cytometry assays and transmission electron microscopy. Western blotting was used to analyse the pathway of iodine-induced apoptosis in osteosarcoma cells. PEG400, silk fibroin solution, polyvinylpyrrolidone iodine (PVP-I), and meglumine diatrizoate (MD) were mixed to produce an imageable hydrogel. A nude mouse model of osteosarcoma was established, and the hydrogel was injected locally into the interior of the osteosarcoma with X-ray guidance. The therapeutic effect and biosafety of the hydrogel were evaluated. Results: Iodine treatment at 18 and 20 µM for 12 h resulted in cell survival rate reduced to 50 ± 2.1% and 50.5 ± 2.7% for MG-63 and Sao-2 cells, respectively (p < 0.01). The proportion of apoptotic cells was significantly higher in the iodine-treatment group than in the control group (p < 0.05), and apoptotic bodies were observed by transmission electron microscopy. Iodine could regulate the death receptor pathway and induce MG-63 and Saos-2 cell apoptosis. The hydrogels were simple to assemble, and gels could be formed within 38 min. A force of less than 50 N was required to inject the gels with a syringe. The hydrogels were readily loaded and led to sustained iodine release over 1 week. The osteosarcoma volume in the PEG-iodine-silk/MD hydrogel group was significantly smaller than that in the other three groups (p < 0.001). Caspase-3 and poly (ADP-ribose) polymerase (PARP) expression levels were significantly higher in the PEG-iodine-silk/MD hydrogel group than in the other three groups (p < 0.001). Haematoxylin and eosin (H&E) staining showed no abnormalities in the heart, liver, spleen, lung, kidney, pancreas or thyroid in any group. Conclusions: Self-assembling imageable silk hydrogels could be injected locally into osteosarcoma tissues with X-ray assistance. With the advantages of good biosafety, low systemic toxicity and minimal invasiveness, self-assembling imageable silk hydrogels provide a promising approach for improving the locoregional control of osteosarcoma.

Acetic acid alters rhizosphere microbes and metabolic composition to improve willows drought resistance.

The adverse effects of drought on plants are gradually exacerbated with global climatic change. Amelioration of the drought stress that is induced by low doses of acetic acid (AA) has been caused great interest in plants. However, whether AA can change soil microbial composition is still unknown. Here, we investigated how exogenous AA regulates the physiology, rhizosphere soil microorganisms and metabolic composition on Salix myrtillacea under drought stress. The physiological results showed that AA could improve the drought tolerance of S. myrtillacea. Azotobacter and Pseudomonas were enriched in the rhizosphere by AA irrigation. AA significantly increased the relative contents of amino acid metabolites (e.g., glycyl-L-tyrosine, l-glutamine and seryl-tryptophan) and decreased the relative contents of phenylpropane metabolites (e.g., fraxetin and sinapyl aldehyde) in soils. The enrichments of Azotobacter and Pseudomonas were significantly correlated with glycyl-L-tyrosine, l-glutamine, seryl-tryptophan, fraxetin and sinapyl aldehyde, which could increase the stress resistance by promoting nitrogen (N) uptake for willows. Furthermore, inoculation with Azotobacter chroococcum and Pseudomonas fluorescens could significantly improve willows drought tolerance. Therefore, our results reveal that the changes of plant physiology, rhizosphere soil microorganisms and metabolic composition induced by AA can improve willows drought resistance by enhancing N uptake.

CAR T Cell Locomotion in Solid Tumor Microenvironment.

The promising outcomes of chimeric antigen receptor (CAR) T cell therapy in hematologic malignancies potentiates its capability in the fight against many cancers. Nevertheless, this immunotherapy modality needs significant improvements for the treatment of solid tumors. Researchers have incrementally identified limitations and constantly pursued better CAR designs. However, even if CAR T cells are armed with optimal killer functions, they must overcome and survive suppressive barriers imposed by the tumor microenvironment (TME). In this review, we will discuss in detail the important role of TME in CAR T cell trafficking and how the intrinsic barriers contribute to an immunosuppressive phenotype and cancer progression. It is of critical importance that preclinical models can closely recapitulate the in vivo TME to better predict CAR T activity. Animal models have contributed immensely to our understanding of human diseases, but the intensive care for the animals and unreliable representation of human biology suggest in vivo models cannot be the sole approach to CAR T cell therapy. On the other hand, in vitro models for CAR T cytotoxic assessment offer valuable insights to mechanistic studies at the single cell level, but they often lack in vivo complexities, inter-individual heterogeneity, or physiologically relevant spatial dimension. Understanding the advantages and limitations of preclinical models and their applications would enable more reliable prediction of better clinical outcomes.

A Low-Voltage Cylindrical Traveling Wave Ultrasonic Motor Incorporating Multilayered Piezoelectric Ceramics.

In-plane bending traveling wave ultrasonic motors (USM), which are compact in structure and flexible in design, have been widely applied in biological engineering, optical engineering, and aerospace engineering. However, the high driving voltage and complicated driving circuit of this kind of USM restrict their further miniaturization and electromechanical integration in these applications and bring some potential safety hazards. To solve this problem, a low-voltage-driving traveling wave USM incorporating cofired multilayer piezoelectric ceramics was proposed in this work. Four cofired piezoelectric ceramics were strategically designed to excite two orthogonal third-order in-plane bending modes with the same frequency of the USM. The principles of traveling wave synthesis and low-voltage-driving of the USM were deduced, and the stator dynamic design and transient dynamic simulation were carried out by finite-element method. The microproperties of cofired piezoelectric multilayer ceramics, the vibration characteristics of the stator, and the mechanical output performance of the USM were tested by experiments. The results indicated that the motor can work as low as 5 [Formula: see text]. A long stroke with a maximum forward and reverse rotational speeds of 187.7 and 176.6 r/min were obtained, respectively, and a maximum stalling torque of 4.8 mN · m at 47.3 kHz under 15 [Formula: see text] was achieved. The results showed that the proposed USM is small, low in driving voltage, and high in torque output, which has promising applications in aerospace, biomedicine, and other fields that require a lightweight and integration of driving devices.

Profiles of immune cell infiltration and immune-related genes in the tumor microenvironment of osteosarcoma cancer.

BACKGROUNDS: Osteosarcomas are one of the most common primary malignant tumors of bone. It primarily occurs in children and adolescents, with the second highest incidence among people over 50 years old. Although there were immense improvements in the survival of patients with osteosarcoma in the past 30 years, targetable mutations and agents of osteosarcomas still have been generally not satisfactory. Therefore, it is of great importance to further explore the highly specialized immune environment of bone, genes related to macrophage infiltration and potential therapeutic biomarkers and targets. METHODS: The 11 expression data sets of OS tissues and the 11 data sets of adjacent non-tumorous tissues available in the GEO database GSE126209 were used to conduct immune infiltration analysis. Then, through WGCNA analysis, we acquired the co-expression modules related to Mast cells activated and performed the GO and KEGG enrichment analysis. Next, we did the survival prognosis analysis and plotted a survival curve. Finally, we analyzed the COX multivariate regression of gene expression on clinical parameters and drew forest maps for visualization by the forest plot package. RESULTS: OS disease-related immune cell populations, mainly Mast cells activated, have higher cell content (p = 0.006) than the normal group. Then, we identified co-expression modules related to Mast cells activated. In sum, a total of 822 genes from the top three strongest positive correlation module MEbrown4, MEdarkslateblue and MEnavajowhite2 and the strongest negative correlation module MEdarkturquoise. From that, we identified nine genes with different levels in immune cell infiltration related to osteosarcoma, eight of which including SORBS2, BAIAP2L2, ATAD2, CYGB, PAMR1, PSIP1, SNAPC3 and ZDHHC21 in their low abundance have higher disease-free survival probability than the group in their high abundances. CONCLUSION: These results could assist clinicians to select targets for immunotherapies and individualize treatment strategies for patients with OS.

Engineered polymer nanoparticles incorporating l-amino acid groups as affinity reagents for fibrinogen.

Synthetic polymer hydrogel nanoparticles (NPs) were developed to function as abiotic affinity reagents for fibrinogen. These NPs were made using both temperature-sensitive N-isopropyl acrylamide (NIPAm) and l-amino acid monomers. Five kinds of l-amino acids were acryloylated to obtain functional monomers: l-phenylalanine (Phe) and l-leucine (Leu) with hydrophobic side chains, l-glutamic acid (Glu) with negative charges, and l-lysine (Lys) and l-arginine (Arg) with positive charges. After incubating the NPs with fibrinogen, γ-globulin, and human serum albumin (HSA) respectively, the NPs that incorporated N-acryloyl-Arg monomers (AArg@NPs) showed the strongest and most specific binding affinity to fibrinogen, when compared with γ-globulin and HSA. Additionally, the fibrinogen-AArg binding model had the best docking scores, and this may be due to the interaction of positively charged AArg@NPs and the negatively charged fibrinogen D domain and the hydrophobic interaction between them. The specific adsorption of AArg@NPs to fibrinogen was also confirmed by the immunoprecipitation assay, as the AArg@NPs selectively trapped the fibrinogen from a human plasma protein mixture. AArg@NPs had a strong selectivity for, and specificity to, fibrinogen and may be developed as a potential human fibrinogen-specific affinity reagent.

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In this study, the concept, research value, and research advances of tree transpiration were concisely narrated. From the perspective of measurement and estimation, we summarized the main calculation methods for water consumption of tree transpiration. By comparing the advantages, disadvantages, applicability, limitations, application status, and applicable scale of different methods, we showed that the measurement methods could be applied to the measurement of water consumption at multiple spatial scales, and that the estimation methods were often applied to the measurement of evapotranspiration at large spatial scales. As the measurement method was the basis of the estimation method, it is necessary to carry out reasonable quality control and evaluation of the measured results of measurement methods, in order to provide data basis for the estimation results of the correction estimation method. Whether it was at a particular large spatial scale or at different spatial scales, the combination of measurement methods and estimation methods could improve the accuracy of evapotranspiration measurement. Improving the accuracy of calculating the dispersion of trees at a large spatial scale in complex underlying surface and harsh climate environments would become a research hotspot but may also be a difficulty in the future. With the continuous progress of science and technology, both measurement devices and methods would be improved, and new methods for accurately measuring the water consumption of forest transpiration would be available.