[Efficacy of Decitabine Combined with Preexcitation Regimen in Treatment of Newly Diagnosed AML Patients Who Did not Respond to Initial Standard Induction Chemotherapy].

OBJECTIVE: To investigate the efficacy of decitabine combined with preexcitation regimen in the treatment of newly diagnosed acute myeloid leukemia (AML) patients who have not been relieved by the first standard induction chemotherapy and its influence on the relative content of regulatory T lymphocytes (Tregs). METHODS: The clinical data of 102 newly diagnosed AML patients (except acute promyelocytic leukemia) who did not relieve after initial standard induction chemotherapy in Shaanxi Provincial People's Hospital from March 2013 to March 2019 were retrospectively analyzed. Fifty-one patients who accepted pre-excitation regimen were divided into regular group, while another 51 patients treated with decitabine combined with pre-excitation regimen were divided into combination group. The efficacy, incidence of toxic and side effects, Core Scale of Quality of Life (QLQ-C30) score before and after treatment, T lymphocyte subsets (CD3+, CD4+, CD4+/CD8+, Tregs) and 3-year overall survival (OS) rate were compared between the two groups. RESULTS: The total effective rate of combination group was 80.39%, which was significantly higher than 62.75% of regular group (P < 0.05). After treatment, the QLQ-C30 score of combination group was 60.27±6.96, which was significantly lower than 65.73±7.96 of regular group (P < 0.001). There was no statistical difference in the incidence of toxic and side effects between the two groups (P >0.05). After treatment, the levels of CD3+, CD4+, CD4+/CD8+ in the combination group were higher than those in the regular group (all P < 0.001), while Treg was lower (P < 0.001). The 3-year OS rate in the combination group was 72.55%, which was significantly higher than 52.94% in the regular group (P < 0.001). CONCLUSION: Decitabine combined with preexcitation regimen has a significant effect on AML patients who have not been alleviated by standard induction chemotherapy in the first course of treatment. It can reduce anti-tumor immune suppression and improve immune function by regulating the relative content of Tregs, thus prolongs survival time and improves life quality of patients without increasing adverse reactions.

Black raspberry-mediated metabolic changes in patients with familial adenomatous polyposis associated with rectal polyp regression.

Familial adenomatous polyposis (FAP) patients face an almost certain 100% risk of developing colorectal cancer, necessitating prophylactic colectomy to prevent disease progression. A crucial goal is to hinder this progression. In a recent clinical trial involving 14 FAP patients, half received 60 g of black raspberry (BRB) powder orally and BRB suppositories at bedtime, while the other half received only BRB suppositories at bedtime over 9 months. This intervention led to a notable reduction in rectal polyps for 11 patients, although 3 showed no response. In this study, we delved into the metabolic changes induced by BRBs in the same patient cohort. Employing mass spectrometry-based non-targeted metabolomics, we analyzed pre- and post-BRB urinary and plasma samples from the 11 responders. The results showed significant alterations in 23 urinary and 6 plasma metabolites, influencing various pathways including polyamine, glutathione metabolism, the tricarboxylic acid cycle, inositol metabolism, and benzoate production. BRBs notably elevated levels of several metabolites associated with these pathways, suggesting a potential mechanism through which BRBs facilitate rectal polyp regression in FAP patients by modulating multiple metabolic pathways. Notably, metabolites derived from BRB polyphenols were significantly increased post-BRB intervention, emphasizing the potential therapeutic value of BRBs in FAP management.

FXR1 stabilizes SNORD63 to regulate blood-tumor barrier permeability through SNORD63 mediated 2'-O-methylation of POU6F1.

How selectively increase blood-tumor barrier (BTB) permeability is crucial to enhance the delivery of chemotherapeutic agents to brain tumor tissues. In this study, we established in vitro models of the blood-brain barrier (BBB) and BTB using endothelial cells (ECs) co-cultured with human astrocytes (AECs) and glioma cells (GECs), respectively. The findings revealed high expressions of the RNA-binding protein FXR1 and SNORD63 in GECs, where FXR1 was found to bind and stabilize SNORD63. Knockdown of FXR1 resulted in decreased expression of tight-junction-related proteins and increased BTB permeability by down-regulating SNORD63. SNORD63 played a role in mediating the 2'-O-methylation modification of POU6F1 mRNA, leading to the downregulation of POU6F1 protein expression. POU6F1 showed low expression in GECs and acted as a transcription factor to regulate BTB permeability by binding to the promoter regions of ZO-1, occludin, and claudin-5 mRNAs and negatively regulating their expressions. Finally, the targeted regulation of FXR1, SNORD63, and POU6F1 expressions, individually or in combination, effectively enhanced doxorubicin passage through the BTB and induced apoptosis in glioma cells. This study aims to elucidate the underlying mechanism of the FXR1/SNORD63/POU6F1 axis in regulating BTB permeability, offering a novel strategy to improve the efficacy of glioma chemotherapy.

Kinetics Conditioning of (Electro) Chemically Stable Zn Anode with pH Regulation Toward Long-Life Zn-Storage Devices.

The safety, low cost, and high power density of aqueous Zn-based devices (AZDs) appeal to large-scale energy storage. Yet, the presence of hydrogen evolution reaction (HER) and chemical corrosion in the AZDs leads to local OH- concentration increasement and the formation of ZnxSOy(OH)z•nH2O (ZHS) by-products at the Zn/electrolyte interface, causing instability and irreversibility of the Zn-anodes. Here, a strategy is proposed to regulate OH- by introducing a bio-sourced/renewable polypeptide (ɛ-PL) as a pH regulator in electrolyte. The consumption of OH- species is evaluated through in vitro titration and cell in vivo in situ attenuated total reflection surface-enhanced infrared absorption spectroscopy at a macroscopic and molecular level. The introduction of ɛ-PL is found to significantly suppress the formation of ZHS and associated side reactions, and reduce the local coordinated H2O of the Zn2+ solvation shell, widening electrochemical stable window and suppressing OH- generation during HER. As a result, the inclusion of ɛ-PL improves the cycle time of Zn/Zn symmetrical cells from 15 to 225 h and enhances the cycle time of aqueous Zn- I2 cells to 1650 h compared to those with pristine electrolytes. This work highlights the potential of kinetical OH- regulation for by-product and dendrite-free AZDs.

Cucumber seed polypeptides regulate RANKL-induced osteoclastogenesis through OPG/RANKL/RANK and NF-κB.

Postmenopausal osteoporosis (PMOP) is a common disease that endangers the health of elderly women. Cucumber seeds have shown excellent therapeutic effects on PMOP, but the mechanism of cucumber seed peptide (CSP) remains unclear. The expression levels of NF-κB and osteoclast-related genes were detected by RT-qPCR. The levels of apoptosis-related proteins were detected by Western blotting. Nuclear translocation of NF-κB p65 and osteoclast formation were detected by immunofluorescence and tartrate-resistant acid phosphatase (TRAP) staining, respectively. ELISA was used to detect the expression levels of OPG, M-CSF, and RANKL. Hematoxylin-eosin (H&E) and TRAP staining were used to observe the effects of CSP on bone formation. In RAW264.7 cells, CSP (0.4 mg/L, 4 mg/L, and 40 mg/L) effectively inhibited the expression of osteoclast-related genes (Cathepsin-K, MT1-MMP, MMP-9, and TRAP). TRAP-positive multinucleated giant cells gradually decreased. Furthermore, NF-κB pathway activation downstream of RANK was inhibited. In bone marrow stromal cells (BMSCs), the expression levels of M-CSF and RANKL gradually decreased, and OPG gradually increased with increasing CSP concentrations. Treatment of RAW264.7 cells with pyrrolidine dithiocarbamate (PDTC, an inhibitor of NF-κB) prevented the formation of osteoclasts. Treatment with different concentrations of CSP effectively decreased the levels of RANKL and M-CSF in rat serum and increased the expression of OPG in the oophorectomy (OVX) rat model. Furthermore, different concentrations of CSP could ameliorate the loss of bone structure and inhibit the formation of osteoclasts in rats. CSP inhibits osteoclastogenesis by regulating the OPG/RANKL/RANK pathway and inhibiting the NF-kB pathway.

Expression profiles and function prediction of tRNA-derived fragments in glioma.

BACKGROUND: Glioblastoma (GBM) is the most aggressive malignant primary brain tumor. The transfer RNA-derived fragments (tRFs) are a new group of small noncoding RNAs, which are dysregulated in many cancers. Until now, the expression and function of tRFs in glioma remain unknown. METHODS: The expression profiles of tRF subtypes were analyzed using the Cancer Genome Atlas (TCGA)-low-grade gliomas (LGG)/GBM dataset. The target genes of tRFs were subjected to Gene Ontology, Kyoto Encyclopedia and Gene set enrichment analysis of Genes and Genomes pathway enrichment analysis. The protein-protein interaction enrichment analysis was performed by STRING. QRT-PCR was performed to detect the expressions of tRFs in human glioma cell lines U87, U373, U251, and human astrocyte cell line SVG p12. Western blot assay was used to detect to the expression of S100A11. The interaction between tRF-19-R118LOJX and S100A11 mRNA 3'UTR was detected by dual-luciferase reporter assay. The effects of tRF-19-R118LOJX, tRF-19-6SM83OJX and S100A11 on the glioma cell proliferation, migration and in vitro vasculogenic mimicry formation ability were examined by CCK-8 proliferation assay, EdU assay, HoloMonitor cell migration assay and tube formation assay, respectively. RESULTS: tRF-19-R118LOJX and tRF-19-6SM83OJX are the most differentially expressed tRFs between LGG and GBM groups. The functional enrichment analysis showed that the target genes of tRF-19-R118LOJX and tRF-19-6SM83OJX are enriched in regulating blood vessel development. The upregulated target genes are linked to adverse survival outcomes in glioma patients. tRF-19-R118LOJX and tRF-19-6SM83OJX were identified to suppress glioma cell proliferation, migration, and in vitro vasculogenic mimicry formation. The mechanism of tRF-19-R118LOJX might be related to its function as an RNA silencer by targeting the S100A11 mRNA 3'UTR. CONCLUSION: tRFs would become novel diagnostic biomarkers and therapeutic targets of glioma, and the mechanism might be related to its post-transcriptionally regulation of gene expression by targeting mRNA 3'UTR.

CircMTA1 promotes glioblastoma angiogenesis by encoding MTA1-134aa.

Glioblastoma multiforme (GBM) is the most malignant brain tumor with rapid angiogenesis. How to inhibit GBM angiogenesis is a key problem to be solved. To explore the targets of inhibiting GBM angiogenesis, this study confirmed that the expression of circMTA1 (hsa_circ_0033614) was significantly upregulated in human brain microvascular endothelial cells exposed to glioma cell-conditioned medium (GECs). The expression of circMTA1 in the cytoplasm was significantly higher than that in the nucleus. Upregulated circMTA1 in GECs can promote cell proliferation, migration, and tube formation. Further exploration of the circularization mechanism of circMTA1 confirmed that KHDRBS1 protein can bind to the upstream and downstream flanking sequences of circMTA1 and promote circMTA1 biogenesis by coordinating Alu element pairing. KHDRBS1 upregulated the proliferation, migration, and tube formation of GECs by promoting the biogenesis of circMTA1. CircMTA1 can encode the protein MTA1-134aa by internal ribosome entry site sequence-mediated translation mechanism, and promote the proliferation, migration, and tube formation of GECs through the encoded MTA1-134aa. This study provides a new target for inhibiting angiogenesis in brain GBM and a new strategy for improving the therapeutic efficacy of GBM.

Recent progress of self-immobilizing and self-precipitating molecular fluorescent probes for higher-spatial-resolution imaging.

Flourished in the past two decades, fluorescent probe technology provides researchers with accurate and efficient tools for in situ imaging of biomarkers in living cells and tissues and may play a significant role in clinical diagnosis and treatment such as biomarker detection, fluorescence imaging-guided surgery, and photothermal/photodynamic therapy. In situ imaging of biomarkers depends on the spatial resolution of molecular probes. Nevertheless, the majority of currently available molecular fluorescent probes suffer from the drawback of diffusing from the target region. This leads to a rapid attenuation of the fluorescent signal over time and a reduction in spatial resolution. Consequently, the diffused fluorescent signal cannot accurately reflect the in situ information of the target. Self-immobilizing and self-precipitating molecular fluorescent probes can be used to overcome this problem. These probes ensure that the fluorescent signal remains at the location where the signal is generated for a long time. In this review, we introduce the development history of the two types of probes and classify them in detail according to different design strategies. In addition, we compare their advantages and disadvantages, summarize some representative studies conducted in recent years, and propose prospects for this field.

Potential Role of Cuproptosis-Related Lncrna in Prognosis and Immunotherapy of Thyroid Carcinoma.

Background: Cuproptosis-related long non-coding RNA (lncRNA) disease is associated with the development and progression of tumors. We aimed to investigate the prediction of cuproptosis-related lncRNA on the prognosis and immunotherapy of patients with thyroid carcinoma (THCA). Methods: The thyroid cancer-associated expression data and lnc RNAs data were downloaded from The Cancer Genome Atlas (TCGA) and Ensembl database. The prognostic model of cuproptosis-related lncRNAs was successfully constructed through Lasso regression analysis and Cox regression analysis. Then, the prognostic value of prognostic model of cuproptosis-related lncRNAs was tested through the survival analysis, ROC curves and nomographic charts. Finally, the prognostic model of cuproptosis-related lncRNAs associated with immunity and mutational load of tumors was analyzed, and potential targeted drugs for THCA were predicted. Results: A cuproptosis-related lncRNA model of THCA (AC026100.1, AF235103.3, LNCSRLR) was successfully constructed, which has an independent prognostic value. Moreover, the cuproptosis-related lncRNA model was associated with immune signatures and mutational load in most tumors, showing its high correlation with the sensitivity of targeted drugs such as 5-Fluorouracil, Bleomycin, Rapamycin and Sunitinib. Conclusion: The cuproptosis-related lncRNA model of THCA has promising applications in the treatment and prognosis of THCA.

Association between serum albumin levels and survival in elderly patients with diffuse large B-cell lymphoma: a single-center retrospective study.

Background: In clinical hematology, diffuse large B-cell lymphoma (DLBCL) is notably heterogeneous and varies in prognosis. Serum albumin (SA) is considered a biomarker of prognostic value in a number of hematologic malignancies. However, current knowledge of the association between SA levels and survival is limited, especially in DLBCL patients aged ≥70 years. Thus, this study sought to assess the prognostic value of SA levels among this age group of patients. Methods: The data of DLBCL patients aged ≥70 years at the Shaanxi Provincial People's Hospital in China from 2010 to 2021 were retrospectively reviewed. The SA levels were measured using standard procedures. The Kaplan-Meier method was used to estimate survival time, and the Cox proportional hazards model for time-to-event data was used to identify potential risk factors. Results: The data of 96 participants were included in the study. The univariate analysis showed that B symptoms, Ann Arbor stage III or IV of the disease, high International Prognostic Index (IPI) scores, high NCCN-IPI scores, and low SA levels were prognostic factors for an undesirable overall survival (OS) rate. The multivariate analysis showed that a high SA level (hazard ratio: 0.43; 95% confidence interval: 0.2-0.88; P=0.022) was an independent prognostic factor of superior outcomes. Conclusions: An SA level ≥4.0 g/dL was identified as an independent biomarker of prognostic value for DLBCL patients aged ≥70 years.

Preparation of ZIF-8/PAN composite nanofiber membrane and its application in acetone gas monitoring.

Znic-based metal-organic framework materials (ZIF-8) show great potential and excellent performance in the fields of sensing and catalysis. However, powdered metal-organic framework makes it easy to lose in the process of application. Herein, we use a simple blending electrostatic spinning method to combine ZIF-8 particles with polyacrylonitrile (PAN) nanofibers. ZIF-8/PAN composite nanofiber membrane. The ZIF-8/PAN nanofiber membrane is characterized by scanning electron microscope (SEM), x-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and N2adsorption-desorption. The results show that the ZIF-8/PAN nanofiber membrane has the characteristic peaks of XRD and FTIR, which are consistent with those of simulated ZIF-8. The specific surface area of ZIF-8/PAN nanofiber membrane increases from 13.5371 to 711.4171 m2g-1due to the introduction of ZIF-8 particles. The sensor using the nanofiber membrane as the gas sensing layer shows good response and linear correlation to different concentrations of acetone gas. The minimum detection limit of the sensor for acetone is 51.9 ppm. The blank control shows that the response of the sensor to acetone is mainly due to the introduction of ZIF-8 particles. In addition, the sensor also shows a good cyclic response to acetone.

High Levels of Extracellular Potassium Can Delay Myxoma Virus Replication by Preventing Release of Virions from the Endosomes.

Potassium (K+) is one of the most abundant cations in the human body. Under normal conditions, the vast majority of K+ is found within cells, and the extracellular [K+] is tightly regulated to within 3.0 to 5.0 mM. However, it has recently been shown that high levels of localized necrosis can increase the extracellular concentration of K+ to above 50 mM. This raises the possibility that elevated extracellular K+ might influence a variety of biological processes that occur within regions of necrotic tissue. For example, K+ has been shown to play a central role in the replication cycles of numerous viral families, and in cases of lytic infection, localized regions containing large numbers of necrotic cells can be formed. Here, we show that the replication of the model poxvirus myxoma virus (MYXV) is delayed by elevated levels of extracellular K+. These increased K+ concentrations alter the cellular endocytic pathway, leading to increased phagocytosis but a loss of endosomal/lysosomal segregation. This slows the release of myxoma virus particles from the endosomes, resulting in delays in genome synthesis and infectious particle formation as well as reduced viral spread. Additionally, mathematical modeling predicts that the extracellular K+ concentrations required to impact myxoma virus replication can be reached in viral lesions under a variety of conditions. Taken together, these data suggest that the extracellular [K+] plays a role in determining the outcomes of myxoma infection and that this effect could be physiologically relevant during pathogenic infection. IMPORTANCE Intracellular K+ homeostasis has been shown to play a major role in the replication of numerous viral families. However, the potential impact of altered extracellular K+ concentrations is less well understood. Our work demonstrates that increased concentrations of extracellular K+ can delay the replication cycle of the model poxvirus MYXV by inhibiting virion release from the endosomes. Additionally, mathematical modeling predicts that the levels of extracellular K+ required to impact MYXV replication can likely be reached during pathogenic infection. These results suggest that localized viral infection can alter K+ homeostasis and that these alterations might directly affect viral pathogenesis.

Resveratrol protects renal damages induced by periodontitis via preventing mitochondrial dysfunction in rats.

OBJECTIVES: Periodontitis is closely associated with kidney disease and reactive oxygen species (ROS) involvement. Mitochondria are the primary source of both endogenous ROS and renal energy. We investigated whether resveratrol (RSV) prevents renal injury and mitochondrial dysfunction in periodontitis rats. METHODS: Thirty male Wistar rats were divided into control, experimental periodontitis (Ep) and Ep-RSV groups. To induce periodontitis, a steel ligature was placed on the cervix of the bilateral first maxillary molars. RSV (50 mg/kg/day) to the Ep-RSV group and vehicle to the Ep and control groups were gavaged. After 8 weeks, alveolar bone loss, pocket depth, gingival blood index and tooth mobility were assessed. Oxidative stress parameters, mitochondrial structure, mitochondrial membrane potential (MMP), mitochondrial ROS, adenosine triphosphate (ATP), sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) were analysed in renal. Renal function and histology were also evaluated. RESULTS: Compared with the control group, the Ep group showed renal structural destruction, elevated oxidative stress levels, mitochondrial structure destruction, MMP loss, mitochondrial ROS accumulation, ATP reduction, and decreased SIRT1 and PGC-1α levels. RSV prevented these destruction (p < 0.05). However, there was no significant impairment in renal function (p > 0.05). CONCLUSIONS: Periodontitis induces mitochondrial dysfunction in renal tissues. Resveratrol exerts a preventive effect on periodontitis-induced kidney injury by preventing mitochondrial dysfunction.

Hypomorphic and dominant-negative impact of truncated SOX9 dysregulates Hedgehog-Wnt signaling, causing campomelia.

Haploinsufficiency for SOX9, the master chondrogenesis transcription factor, can underlie campomelic dysplasia (CD), an autosomal dominant skeletal malformation syndrome, because heterozygous Sox9 null mice recapitulate the bent limb (campomelia) and some other phenotypes associated with CD. However, in vitro cell assays suggest haploinsufficiency may not apply for certain mutations, notably those that truncate the protein, but in these cases in vivo evidence is lacking and underlying mechanisms are unknown. Here, using conditional mouse mutants, we compared the impact of a heterozygous Sox9 null mutation (Sox9+/-) with the Sox9+/Y440X CD mutation that truncates the C-terminal transactivation domain but spares the DNA-binding domain. While some Sox9+/Y440X mice survived, all Sox9+/- mice died perinatally. However, the skeletal defects were more severe and IHH signaling in developing limb cartilage was significantly enhanced in Sox9+/Y440X compared with Sox9+/-. Activating Sox9Y440X specifically in the chondrocyte-osteoblast lineage caused milder campomelia, and revealed cell- and noncell autonomous mechanisms acting on chondrocyte differentiation and osteogenesis in the perichondrium. Transcriptome analyses of developing Sox9+/Y440X limbs revealed dysregulated expression of genes for the extracellular matrix, as well as changes consistent with aberrant WNT and HH signaling. SOX9Y440X failed to interact with ß-catenin and was unable to suppress transactivation of Ihh in cell-based assays. We propose enhanced HH signaling in the adjacent perichondrium induces asymmetrically localized excessive perichondrial osteogenesis resulting in campomelia. Our study implicates combined haploinsufficiency/hypomorphic and dominant-negative actions of SOX9Y440X, cell-autonomous and noncell autonomous mechanisms, and dysregulated WNT and HH signaling, as the cause of human campomelia.

Preparation and characterization of a novel intelligent starch/gelatin binary film containing purple sweet potato anthocyanins for Flammulina velutipes mushroom freshness monitoring.

In this study, intelligent food package was developed and characterized by loading purple sweet potato polyphenolic extract (SPS) into starch/gelatin film. The application of this film in indicating the freshness of Flammulina velutipes was also determined. The color of SPS buffer changed from red to blue and final yellow when pH increasing from 3 to 10. The blending film with starch/gelatin ratio of 1:1 wt showed a minimum water vapor permeability of 6.26 × 10-11 gs-1 m-1 Pa-1. The value of elongation at break and tensile strength of the starch/gelatin film with starch/gelatin ratio of 1:1 wt increased to 78.89 % and 11.70 MPa. Upon its application to monitor of F. velutipes freshness level, SG11 film color changed from initially green to purplish gray and finally to yellow as F. velutipes deteriorated post storage. Our results suggested that SG11 films could be used as an intelligent packaging material in the future for other food products.

Effects of Black Raspberry Supplementation on Methylation Pathways in Vav-creAsxl1fl/flTet2fl/fl Double Knockout Mice with Early-stage Myelodysplastic Syndrome.

Myelodysplastic syndromes (MDS) are a subset of myeloid malignancies defined by clonality of immature hematopoietic stem cells that leads to faulty blood cell development. These syndromes can lead to an increased risk of infection and may transform into acute myeloid leukemia, making it critical to determine effective treatments for the condition. While hypomethylating agents such as azacitidine and decitabine, as well as stem cell transplants, have been delineated as favored treatments for MDS, not all patients are physiologically receptive to these treatments. However, black raspberries (BRBs) have been shown to exert hypomethylating effects in various malignancies, with minimal adverse effects and thus a broader range of potential candidacies. This study aimed to investigate the potential of BRBs to exert such effects on MDS using Addition of Sex Combs Like/Tet Methylcytosine Dioxygenase 2 (Asxl1/Tet2) double knockout mice (Vav-cre Asxl1fl/fl Tet2fl/fl), which typically manifest symptoms around 25 weeks of age, mirroring genetic mutations found in humans with MDS. Following a 12-week dietary supplementation of Vav-cre Asxl1fl/fl Tet2fl/fl mice with 5% BRBs, we observed both hyper- and hypomethylation at multiple transcription start sites and intragenic locations linked to critical pathways, including hematopoiesis. This methylation profile may have implications for delaying the onset of MDS, prompting a need for in-depth investigation. Our results emphasize the importance of exploring whether an extended BRB intervention can effectively alter MDS risk and elucidate the relationship between BRB-induced methylation changes, thus further unlocking the potential benefits of BRBs for MDS patients.

Co-encapsulation of chlorogenic acid and cinnamaldehyde essential oil in Pickering emulsion stablized by chitosan nanoparticles.

Most of the current research only explored the loading of an active substance in active packaging. In this study, cinnamaldehyde essential oil (CEO) and chlorogenic acid (CA) were co-encapsulated in chitosan (CS) nanoparticles based Pickering emulsion. The morphology and wettability of CS-CA particles were determined. In addition, physicochemical characterizations and stability of the Pickering emulsion were also investigated. Results showed that the wettability of nanoparticles was improved with increasing the ratios of CS to CA, which is helpful to stabilize the emulsion. CEO Pickering emulsion was stabilized by CS-CA nanoparticles and CEO emulsion showed the best stability by using CS-CA nanoparticles with the ratios of CS to CA 1:0.75 with the minimum creaming index value of 26.5 ± 4.6% after 5 days of storage. These overall results presented in this work demonstrate, for the first time, the potential of Pickering emulsion for the co-encapsulation of water-soluble and water-insoluble ingredients.

Wire + Arc Additive Manufacturing and Heat Treatment of Super Martensitic Stainless Steel with a Refined Microstructure and Excellent Mechanical Properties.

Due to the advantages of relatively low cost, increased energy efficiency, increased deposition rate, and the capacity to create medium to large scale components, wire + arc additive manufacturing (WAAM) has gained growing interest. Super martensitic stainless steel (SMSS) combines outstanding strength, ductility, and corrosion resistance, making it a great option for WAAM. In the present work, an SMSS component was successfully produced by WAAM. Additionally, the influence of post-manufactured heat treatment on the microstructural characteristics and mechanical properties of SMSS components was systematically examined. A microstructural analysis of the as-printed and heat-treated samples revealed the formation of typical martensite and a small amount of retained austenite. However, the sample heat-treated by solutionizing at 1050 °C for 1 h followed by aging at 400 °C for 2 h exhibited a finer martensitic structure with an effective grain size of 5.6 µm compared to as-printed sample, leading to an increase in ultimate tensile strength from 1054 ± 6 MPa to 1141 ± 3 MPa with a concomitant increase in elongation from 7.8 ± 0.4% to 12.6 ± 0.2%. Additionally, the fracture morphology of the solution + aging sample demonstrated a more uniform distribution and greater mean size of dimples, indicating better ductility.

Monoclonal antibody Daratumumab promotes macrophage-mediated anti-myeloma phagocytic activity via engaging FC gamma receptor and activation of macrophages.

Daratumumab (DAR) is novel human anti-CD38 IgG1, high-affinity human monoclonal antibody having broad-spectrum killing activity. The antibody is recommended to treat multiple myeloma. Recently Antibody-dependent cellular phagocytosis (ADCP) have been identified as the potential mechanism of DAR in addition to complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC). In the present study we evaluated the effect of Daratumumab on other effector cells of multiple myeloma. Luciferase+ MM.1R GFP cells were selected for the study. For immune-compromised multiple myeloma tumour xenograft mouse model we used severe combined immunodeficient beige (SCID-beige), NOD SCID gamma (NSG) and C57Bl/6j mice. Bioluminescence imaging was carried by injecting luciferin, and in vivo confocal microscopy was done for tracing bone marrow niches. Spleen and tumours were submitted to immunophenotypic analysis. MTT assay was done for cell proliferation studies. We established tumour xenograft mouse model. It was found that DAR showed significant anti-tumour effect in tumour xenograft multiple myeloma mice. We found that DAR showed anti-tumour activity via Fc-FcγR interaction with macrophages. DAR induced phenotypic activation of macrophages in mice and resulted in ADCP of cancerous cells via interacting Fc-FcγR in vitro. The study suggested that DAR exerted anti-tumour activity in multiple myeloma by interacting with Fc-FcγR.