Using Dual-source Photon-counting Detector CT to Simultaneously Quantify Fat and Iron Content: A Phantom Study.

RATIONALE AND OBJECTIVES: To evaluate the feasibility of using photon-counting detector computed tomography (PCD CT) to simultaneously quantify fat and iron content MATERIALS AND METHODS: Phantoms with pure fat, pure iron and fat-iron deposition were scanned by two tube voltages (120 and 140 kV) and two image quality (IQ) settings (80 and 145). Using an iron-specific three-material decomposition algorithm, virtual noniron (VNI) and virtual iron content (VIC) images were generated at quantum iterative reconstruction (QIR) strength levels 1-4. RESULTS: Significant linear correlations were observed between known fat content (FC) and VNI for pure fat phantoms (r = 0.981-0.999, p < 0.001) and between known iron content (IC) and VIC for pure iron phantoms (r = 0.897-0.975, p < 0.001). In fat-iron phantoms, the measurement for fat content of 5-30% demonstrated good linearity between FC and VNI (r = 0.919-0.990, p < 0.001), and VNI were not affected by 75, 150, and 225 µmol/g iron overload (p = 0.174-0.519). The measurement for iron demonstrated a linear range of 75-225 µmol/g between IC and VIC (r = 0.961-0.994, p < 0.001) and VIC was not confounded by the coexisting 5%, 20%, and 30% fat deposition (p = 0.943-0.999). The Bland-Altman of fat and iron measurements were not significantly different at varying tube voltages and IQ settings (all p > 0.05). No significant difference in VNI and VIC at QIR 1-4. CONCLUSION: PCD CT can accurately and simultaneously quantify fat and iron, including scan parameters with lower radiation dose.

Orally Administrated Hydrogel Harnessing Intratumoral Microbiome and Microbiota-Related Immune Responses for Potentiated Colorectal Cancer Treatment.

The intestinal and intratumoral microbiota are closely associated with tumor progression and response to antitumor treatments. The antibacterial or tumor microenvironment (TME)-modulating approaches have been shown to markedly improve antitumor efficacy, strategies focused on normalizing the microbial environment are rarely reported. Here, we reported the development of an orally administered inulin-based hydrogel with colon-targeting and retention effects, containing hollow MnO2 nanocarrier loaded with the chemotherapeutic drug Oxa (Oxa@HMI). On the one hand, beneficial bacteria in the colon specifically metabolized Oxa@HMI, resulting in the degradation of inulin and the generation of short-chain fatty acids (SCFAs). These SCFAs play a crucial role in modulating microbiota and stimulating immune responses. On the other hand, the hydrogel matrix underwent colon microbiota-specific degradation, enabling the targeted release of Oxa and production of reactive oxygen species in the acidic TME. In this study, we have established, for the first time, a microbiota-targeted drug delivery system Oxa@HMI that exhibited high efficiency in colorectal cancer targeting and colon retention. Oxa@HMI promoted chemotherapy efficiency and activated antitumor immune responses by intervening in the microbial environment within the tumor tissue, providing a crucial clinical approach for the treatment of colorectal cancer that susceptible to microbial invasion.

Effects of cold atmospheric plasma pre-treatment on maintaining the quality of ready-to-eat drunken red shrimp (Solenocera crassicornis) stored at chilled conditions.

This present study investigated the effect of cold atmospheric plasma (CAP) pre-treatment on the quality of ready-to-eat drunken red shrimp (Solenocera crassicornis) during chilled storage. The shrimp were pre-treated with the CAP at 40 kV and 36 kH for 100 s in a plasma generating equipment before the drunken treatment and compared with an untreated control sample. The results showed that the CAP pre-treatment significantly inhibited the total viable count (TVC) values, total volatile basic nitrogen (TVB-N) content, and polyphenol oxidase (PPO) activity of the drunken shrimp compared to the control treatment. Furthermore, the CAP pre-treatment also significantly maintained the myofibrillar protein (MP) content, texture properties, and a more stable histological structure of muscle fibers compared to the control. High-throughput sequencing results confirmed that the CAP pre-treatment significantly reduced the diversity and abundance of several bacteria in the shrimp. Gas chromatography-ion mobility spectrometry (GC-IMS) analysis detected that the CAP pre-treatment effectively maintained the stability of volatile organic compounds (VOCs). These findings provide valuable theoretical support for the processing and storage of drunken shrimp.

Clinical feasibility of deep learning reconstruction in liver diffusion-weighted imaging: Improvement of image quality and impact on apparent diffusion coefficient value.

PURPOSE: Diffusion-weighted imaging (DWI) of the liver suffers from low resolution, noise, and artifacts. This study aimed to investigate the effect of deep learning reconstruction (DLR) on image quality and apparent diffusion coefficient (ADC) quantification of liver DWI at 3 Tesla. METHOD: In this prospective study, images of the liver obtained at DWI with b-values of 0 (DWI0), 50 (DWI50) and 800 s/mm2 (DWI800) from consecutive patients with liver lesions from February 2022 to February 2023 were reconstructed with and without DLR (non-DLR). Image quality was assessed qualitatively using Likert scoring system and quantitatively using signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and liver/parenchyma boundary sharpness from region-of-interest (ROI) analysis. ADC value of lesion were measured. Phantom experiment was also performed to investigate the factors that determine the effect of DLR on ADC value. Qualitative score, SNR, CNR, boundary sharpness, and apparent diffusion coefficients (ADCs) for DWI were compared using paired t-test and Wilcoxon signed rank test. P < 0.05 was considered statistically significant. RESULTS: A total of 85 patients with 170 lesions were included. DLR group showed a higher qualitative score than the non-DLR group. for example, with DWI800 the score was 4.77 ± 0.52 versus 4.30 ± 0.63 (P < 0.001). DLR group also showed higher SNRs, CNRs and boundary sharpness than the non-DLR group. DLR reduced the ADC of malignant tumors (1.105[0.904, 1.340] versus 1.114[0.904, 1.320]) (P < 0.001), but there was no significant difference in the diagnostic value of malignancy for DLR and non-DLR groups (P = 57.3). The phantom study confirmed a reduction of ADC in images with low resolution, and a stronger reduction of ADC in heterogeneous structures than in homogeneous ones (P < 0.001). CONCLUSIONS: DLR improved image quality of liver DWI. DLR reduced the ADC value of lesions, but did not affect the diagnostic performance of ADC in distinguishing malignant tumors on a 3.0-T MRI system.

Kaempferol attenuates carbon tetrachloride (CCl4)-induced hepatic fibrosis by promoting ASIC1a degradation and suppression of the ASIC1a-mediated ERS.

BACKGROUND: Kaempferol is a flavonoid derived from the herb, Kaempferia galanga L., in addition to exhibiting a wide range of pharmacological properties, kaempferol is also an anti-inflammatory, anti-lipid metabolizing, and anti-oxidative stress agent. The underlying molecular mechanisms of its effects on vascular endothelial growth factor (VEGF) secretion and activation of hepatic stellate cells (HSCs) are yet unknown. Activated HSCs induces VEGF release and extracellular matrix (ECM) accumulation which are important factors in hepatic fibrosis. PURPOSE: Our aim is to explore how kaempferol may affect hepatic fibrosis and the mechanisms behind its effects. METHODS: The in vivo model was Sprague-Dawley rats induced with carbon tetrachloride (CCl4). Histological staining was used to observe histological features of the liver. The levels of (alanine aminotransferase) ALT and (aspartate aminotransferase) AST were detected by the corresponding kits. Platelet-derived growth factor (PDGF) was used to stimulate the HSC-T6 rat hepatic stellate cells. The mechanisms underlying this process were investigated using a variety of molecular approaches, including immunofluorescence, RT-qPCR, and western blotting. Moreover, intracellular Ca2+ were observed by laser confocal microscope. RESULTS: It was found that kaempferol significantly reduced the expression of ASIC1a, VEGF, α-SMA and Collagen-I proteins in a model of CCl4-induced hepatic fibrosis in rats. In HSC-T6, kaempferol inhibits activation of HSCs by decreasing expression of ASIC1a, eIF2α, p-eIF2α and ATF-4. Laser confocal fluorescence showed that kaempferol inhibited Ca2+ influx and reduced Ca2+ concentration around the endoplasmic reticulum. Molecular docking and cellular thermal shift assay (CETSA) results further indicated that kaempferol interacted with ASIC1a. We found that kaempferol may promote the degradation of ASIC1a and inhibited ASIC1a- mediated upregulation of ERS. CONCLUSION: The data from our in vivo experiments demonstrate that kaempferol effectively attenuates hepatic fibrosis. In vitro studies we further propose a novel mechanism of kaempferol against hepatic fibrosis which can interact with ASIC1a and promote ASIC1a degradation while inhibiting the activation and VEGF release of HSCs by suppressing the ASIC1a-eIF2α-ATF-4 signaling pathway.

Acid-sensitive ion channel 1a regulates TNF-α expression in LPS-induced acute lung injury via ERS-CHOP-C/EBPα signaling pathway.

BACKGROUND: Acute lung injury (ALI) is the local inflammatory response of the lungs involved in a variety of inflammatory cells. Macrophages are immune cells and inflammatory cells widely distributed in the body. Acid-sensitive ion channel 1a (ASIC1a) is involved in the occurrence of ALI, but the mechanism is still unclear. METHODS: Kunming mouse were stimulated by Lipopolysaccharides (LPS) to establish ALI model in vivo, and RAW264.7 cells were stimulated by LPS to establish inflammatory model in vitro. Amiloride was used as a blocker of ASIC1a to treat mice, and dexamethasone was used as a positive drug for ALI. After blockers and RNAi blocked or silenced the expression of ASIC1a, the expressions of ASIC1a, endoplasmic reticulum-related proteins GRP78, CHOP, C/EBPα and TNF-α were detected. The Ca2+ concentration was measured by a laser confocal microscope. The interaction between CHOP and C/EBPα and the effect of C/EBPα on the activity of TNF-α promoter were detected by immunoprecipitation and luciferase reporter. RESULTS: The expressions of ASIC1a and TNF-α were increased significantly in LPS group. After the blocker and RNAi blocked or silenced ASIC1a, the expressions of TNF-α, GRP78, CHOP were reduced, and the intracellular Ca2+ influx was weakened. The results of immunoprecipitation showed that CHOP and C/EBPα interacted in the macrophages. After silencing CHOP, C/EBPα expression was increased, and TNF-α expression was decreased. The results of the luciferase reporter indicated that C/EBPα directly binds to TNF-α. CONCLUSION: ASIC1a regulates the expression of TNF-α in LPS-induced acute lung injury via ERS-CHOP-C/EBPα signaling pathway.

A miRNA-based gene therapy nanodrug synergistically enhances pro-inflammatory antitumor immunity against melanoma.

MicroRNA (miRNA)-based gene therapy is a robust approach to treating human cancers. However, the low target specificity and safety issues associated with viral vectors have limited the clinical use of miRNA therapeutics. In the present study, we aimed to develop a biocompatible nanocarrier to deliver the tumor suppressor miR-30a-5p for gene therapy of ocular melanoma. The quasi-mesoporous magnetic nanospheres (MMNs) were prepared by polyelectrolytes-mediated self-assembling Fe3O4 nanocrystals; the cationic polymer capped quasi-mesoporous inner tunnels of the MMNs facilitate high miRNA loading and protect from nuclease degradation. Then, the outer layer of the MMNs was modified with a disulfide bond bridged very low molecular weight polyethyleneimine (PEI) network to form redox-responsive nanospheres (rMMNs) that enhance the miRNA payload and enable miRNA release under glutathione-dominant tumor microenvironment. The miR-30a-5p loaded rMMNs nanodrug (miR-30a-5p@rMMNs) upregulated miR-30a-5p level and inhibited malignant phenotypes of ocular melanoma by targeting the transcription factor E2F7 both in vitro and in vivo. Additionally, rMMNs act as an enhancer to increase cancer cell apoptosis by modulating M1-like macrophage polarization and activating Fenton reaction. Thus, the rMMNs is a promising miRNA carrier for gene therapy and could enhance pro-inflammatory immunity in melanoma and other cancers. STATEMENT OF SIGNIFICANCE: • miR-30a-5p@rMMNs inhibited malignant phenotypes of ocular melanoma both in vitro and in vivo. • The rMMNs promoted M1 macrophage polarization thus synergistically enhancing pro-inflammatory anti-tumor immunity against melanoma. • The rMMNs showed no obvious toxicity under the injection dose.

Tumor microenvironment-regulating nanomedicine design to fight multi-drug resistant tumors.

The tumor microenvironment (TME) is a very cunning system that enables tumor cells to escape death post-traditional antitumor treatments through the comprehensive effect of different factors, thereby leading to drug resistance. Deep insights into TME characteristics and tumor resistance encourage the construction of nanomedicines that can remodel the TME against drug resistance. Tremendous interest in combining TME-regulation measurement with traditional tumor treatment to fight multidrug-resistant tumors has been inspired by the increasing understanding of the role of TME reconstruction in improving the antitumor efficiency of drug-resistant tumor therapy. This review focuses on the underlying relationships between specific TME characteristics (such as hypoxia, acidity, immunity, microorganisms, and metabolism) and drug resistance in tumor treatments. The exciting antitumor activities strengthened by TME regulation are also discussed in-depth, providing solutions from the perspective of nanomedicine design. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.

Avapritinib versus Placebo in Indolent Systemic Mastocytosis.

BACKGROUND: Indolent systemic mastocytosis (ISM) is a clonal mast-cell disease driven by the KIT D816V mutation. We assessed the efficacy and safety of avapritinib versus placebo, both with best supportive care, in patients with ISM. METHODS: We randomized patients with moderate to severe ISM (total symptom score [TSS] of ≥28; scores range from 0 to 110, with higher numbers indicating more severe symptoms) two to one to avapritinib 25 mg once daily (n=141) or placebo (n=71). The primary end point was mean change in TSS based on the 14-day average of patient-reported severity of 11 symptoms. Secondary end points included reductions in serum tryptase and blood KIT D816V variant allele fraction (≥50%), reductions in TSS (≥50% and ≥30%), reduction in bone marrow mast cells (≥50%), and quality of life measures. RESULTS: From baseline to week 24, avapritinib-treated patients had a decrease of 15.6 points (95% CI, −18.6 to −12.6) in TSS compared to a decrease of 9.2 points (−13.1 to −5.2) in the placebo group; P<0.003. From baseline to Week 24, 76/141 patients (54%; 45% to 62%) in the avapritinib group compared to 0/71 patients in the placebo group achieved a ≥50% reduction in serum tryptase level; P<0.001. Edema and increases in alkaline phosphatase were more common with avapritinib than placebo; there were few treatment discontinuations because of adverse events. CONCLUSIONS: In this trial, avapritinib was superior to placebo in reducing uncontrolled symptoms and mast-cell burden in patients with ISM. The long-term safety and efficacy of this approach for patients with ISM remain the focus of the ongoing trial. (Funded by Blueprint Medicines Corporation; ClinicalTrials.gov number, NCT03731260.)

N-phenethyl-5-phenylpicolinamide alleviates inflammation in acute lung injury by inhibiting HIF-1α/glycolysis/ASIC1a pathway.

AIMS: Acute lung injury (ALI) is triggered by an acute inflammatory response. Lipopolysaccharide (LPS) is recognized as an important participant in the pathogenesis of sepsis, which may induce ALI. N-phenethyl-5-phenylpicolinamide (N5P) is a newly synthesized HIF-1α inhibitor. The purpose of the present study was to investigate the potential protective effects of N5P on LPS-induced ALI and the underlying mechanisms. MAIN METHODS: In vivo experiment, the ALI rat model was induced by intratracheal injection of LPS, and various concentrations of N5P were injected intraperitoneally before LPS administration. In vitro experiment, RAW264.7 macrophages were administrated LPS and N5P to detect inflammatory cytokine changes. HIF-1α overexpression plasmid (HIF1α-OE) and granulocyte-macrophage colony-stimulating factor (GM-CSF), a glycolysis agonist, were used to examine the relationship between the HIF-1α/glycolysis/ASIC1a pathway. KEY FINDINGS: Pretreatment with N5P inhibited not only the histopathological changes that occurred in the lungs but also lung dysfunction in LPS-induced ALI. N5P also decreased the levels of lactic acid in lung tissue and arterial blood, and inflammatory factors IL-1ß and IL-6 levels in serum. LPS increased HIF-1α, glycolysis proteins GLUT1, HK2, ASIC1a, IL-1ß, IL-6, and these changes were reversed by N5P in primary alveolar macrophages and RAW264.7 macrophages. Overexpression of HIF-1α significantly increased glycolysis genes and ASIC1a as well as inflammatory cytokines. Excessive glycolysis levels weaken the ability of N5P to inhibit inflammation. SIGNIFICANCE: N5P may alleviate inflammation in ALI through the HIF-1α/glycolysis/ASIC1a signaling pathway. The present findings have provided pertinent information in the assessment of N5P as a potential, future therapeutic drug for ALI.

Proteotranscriptomics of ocular adnexal B-cell lymphoma reveals an oncogenic role of alternative splicing and identifies a diagnostic marker.

BACKGROUND: Ocular adnexal B-cell lymphoma (OABL) is a rare subtype of non-Hodgkin lymphoma. The molecular characteristics of OABL remain poorly understood. We performed an integrated study to investigate the proteotranscriptome landscape and identify novel molecular characteristics and biomarkers of OABL. METHODS: Integrated quantitative proteome and transcriptome were performed on 40 OABL 12 idiopathic orbital inflammation, 6 reactive lymphoid hyperplasia, and 13 aesthetic orbital plastic surgery specimens. Complete clinicopathologic and prognostic data of the patients were recorded. RESULTS: We identified high global protein-mRNA concordance as a novel characteristic of OABL. High concordance was related to OABL recurrence. By integrated expression profile, motif enrichment and trend analysis, we found that alternative splicing is inflammation-independently dysregulated in OABL. After portraying the aberrant alternative splicing event landscape, we demonstrated the oncogenic role of ADAR, a core splicing regulator that regulates the splicing of Rho GTPase and cell cycle members. We found that ADAR regulates cell proliferation and Rho GTPase inhibitor sensitivity of lymphoma. We identified DNAJC9 as a potential biomarker for OABL in proteomic analyses. Immunohistochemistry and immunofluorescent staining showed the nuclear staining of DNAJC9 was significantly higher in extranodal marginal zone lymphomas compared with inflammation specimens. CONCLUSIONS: These results provide an integrated gene expression profiling and demonstrate that high global protein-mRNA concordance is a prognosis-related molecular characteristic of OABL. We portray the alternative splicing events landscape of OABL, and reveal the oncogenic role of ADAR. We identified strong nuclear staining of DNAJC9 as a promising pathology diagnostic biomarker for extranodal marginal zone lymphomas.

Tomoelastography based on multifrequency MR elastography predicts liver function reserve in patients with hepatocellular carcinoma: a prospective study.

BACKGROUND: Estimating liver function reserve is essential for preoperative surgical planning and predicting post-hepatectomy complications in patients with hepatocellular carcinoma (HCC). We investigated hepatic viscoelasticity quantified by tomoelastography, a multifrequency magnetic resonance elastography technique, to predict liver function reserve. METHODS: One hundred fifty-six patients with suspected HCC (mean age, 60 ± 1 years; 131 men) underwent preoperative tomoelastography examination between July 2020 and August 2021. Sixty-nine were included in the final analysis, and their 15-min indocyanine green retention rates (ICG-R15s) were obtained to determine liver function reserve. Tomoelastography quantified the shear wave speed (c, m/s), which represents stiffness, and loss angle (φ, rad), which represents fluidity. Both were correlated with the ICG-R15. A prediction model based on logistic regression for major hepatectomy tolerance (ICG-R15 ≥ 14%) was established. RESULTS: Patients were assigned to either the ICG-R15 < 14% (n = 50) or ICG-R15 ≥ 14% (n = 19) group. Liver c (r = 0.617) and φ (r = 0.517) were positively correlated with the ICG-R15 (both p < 0.001). At fibrosis stages F1-2, φ was positively correlated with the ICG-R15 (r = 0.528; p = 0.017), but c was not (p = 0.104). At stages F3-4, c (r = 0.642; p < 0.001) and φ (r = 0.377; p = 0.008) were both positively correlated with the ICG-R15. The optimal cutoffs of c and φ for predicting ICG-R15 ≥ 14% were 2.04 m/s and 0.79 rad, respectively. The area under the receiver operating characteristic curve was higher for c (0.892) than for φ (0.779; p = 0.045). CONCLUSIONS: Liver stiffness and fluidity, quantified by tomoelastography, were correlated with liver function and may be used clinically to noninvasively assess liver function reserve and stratify treatments.

Efficacy and safety of avapritinib in previously treated patients with advanced systemic mastocytosis.

Advanced systemic mastocytosis (AdvSM) is a rare myeloid neoplasm, driven by the KIT D816V mutation in >90% of patients. Avapritinib, a potent, highly selective D816V-mutant KIT inhibitor, is approved for treatment of adults with AdvSM by the US Food and Drug Administration, regardless of prior therapy, and the European Medicines Agency for patients with prior systemic therapy, based on EXPLORER (#NCT02561988; clinicaltrials.gov) and PATHFINDER (#NCT03580655; clinicaltrials.gov) clinical studies. We present latest pooled efficacy and safety analyses from patients who received ≥1 systemic therapy prior to avapritinib in EXPLORER/PATHFINDER. Overall response rate in response-evaluable patients (n = 31) was 71% (95% confidence interval: 52% to 86%; 22/31), including 19% (6/31) with complete remission (CR)/CR with partial recovery of peripheral blood counts (CRh). Median time to response was 2.3 months, median time to CR/CRh was 7.4 months, and median duration of response (DOR) was not reached. Reductions ≥50% in bone marrow mast cell infiltration (89%), KIT D816V variant allele fraction (66%), serum tryptase (89%), and reductions ≥35% in spleen size (70%) occurred in most patients. Median OS was not reached (median follow-up 17.7 months). Avapritinib was effective in all AdvSM subtypes, regardless of number/type of prior therapies or poor prognostic somatic mutations. Treatment-related adverse events (TRAEs) were observed in 94% of patients, most commonly grade 1/2; 57% had TRAEs of at least grade 3; 81% remained on treatment at 6 months. Avapritinib in adults with AdvSM who received prior systemic therapy was generally well tolerated, with high response rates regardless of prior systemic therapy.

Recent Advances in Acid-sensitive Ion Channels in Central Nervous System Diseases.

Acid-sensitive ion channels (ASICs) are cationic channels activated by extracellular protons and widely distributed in the nervous system of mammals. It belongs to the ENaC/DEG family and has four coding genes: ASIC1, ASIC2, ASIC3, and ASIC4, which encode eight subunit proteins: ASIC1a, ASIC1b, ASIC1b2, ASIC2a, ASIC2b, ASIC3, ASIC4, and ASIC5. Different subtypes of ASICs have different distributions in the central nervous system, and they play an important role in various physiological and pathological processes of the central nervous system, including synaptic plasticity, anxiety disorders, fear conditioning, depressionrelated behavior, epilepsy, Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis, malignant Glioma, pain, and others. This paper reviewed the recent studies of ASICs on the central nervous system to improve the understanding of ASICs' physiological functions and pathological effects. This article also references studying the molecular mechanisms and therapeutic measures of nervous system-related diseases.

Regulation of epigenetic homeostasis in uveal melanoma and retinoblastoma.

Uveal melanoma (UM) and retinoblastoma (RB), which cause blindness and even death, are the most frequently observed primary intraocular malignancies in adults and children, respectively. Epigenetic studies have shown that changes in the epigenome contribute to the rapid progression of both UM and RB following classic genetic changes. The loss of epigenetic homeostasis plays an important role in oncogenesis by disrupting the normal patterns of gene expression. The targetable nature of epigenetic modifications provides a unique opportunity to optimize treatment paradigms and establish new therapeutic options for both UM and RB with these aberrant epigenetic modifications. We aimed to review the research findings regarding relevant epigenetic changes in UM and RB. Herein, we 1) summarize the literature, with an emphasis on epigenetic alterations, including DNA methylation, histone modifications, RNA modifications, noncoding RNAs and an abnormal chromosomal architecture; 2) elaborate on the regulatory role of epigenetic modifications in biological processes during tumorigenesis; and 3) propose promising therapeutic candidates for epigenetic targets and update the list of epigenetic drugs for the treatment of UM and RB. In summary, we endeavour to depict the epigenetic landscape of primary intraocular malignancy tumorigenesis and provide potential epigenetic targets in the treatment of these tumours.

Analysis of volatile compounds and flavor fingerprint in hairtail (Trichiurus lepturus) during air-drying using headspace-gas chromatography-ion mobility spectrometry (HS-GC-IMS).

In the present study, changes in volatile compounds during processing were analyzed using the headspace-gas chromatography-ion mobility spectrometry (HS-GC-IMS), to investigate the generation of aroma in hairtails (Trichiurus lepturus) during air-drying. Physicochemical indices, such as moisture content and thiobarbituric acid reactive substances (TBARS), were also detected. Flavor fingerprints were studied and developed to distinguish the samples of fresh hairtails (0 day) from air-dried hairtails (2 and 4 days). A total of 75 volatile organic compounds (VOCs) were identified in hairtails, in which alcohols, aldehydes, ketones, and esters were the principal contributors to the formation of the overall flavor of hairtails during air-drying. Seven flavor compounds (ethanol, 3-methyl-1-butanol, 1-pentanol, hexanal, octanal, benzaldehyde, and 3-methylbutanal), two flavor compounds (acetoin and dimethyl sulfide), and eight flavor compounds (1-hexanol, 1-octen-3-ol, nonanal, heptanal, 2-heptanone, ethyl acetate, trimethylamine, and ammonia) were identified in 0, 2, and 4 air-dried hairtails as biomarkers, respectively. The results showed that HS-GC-IMS could detect VOCs in different air-dried hairtails rapidly and comprehensively.

Novel insights into exosomal circular RNAs: Redefining intercellular communication in cancer biology.

Exosomes, a special type of membrane-bound extracellular vesicle regarded as an ideal carrier for intercellular messages, play an essential role in intercellular communication both locally and systematically. Recent studies have reported that circular RNAs (circRNAs), members of the noncoding RNA family, are abundant and stable in exosomes. As an essential mediator of intercellular communication within cancer cells or between cancer cells and noncancerous cells, exosomal circRNAs participate in multiple aspects of cancer. In this review, we summarize the biogenesis, properties and functions of exosomal circRNAs. In particular, we describe their intercellular transfer in the tumour microenvironment and associate their biological functions with different phenotypes of cancer. Finally, we discuss potential clinical applications in the future.

Scaffold 3D-Printed from Metallic Nanoparticles-Containing Ink Simultaneously Eradicates Tumor and Repairs Tumor-Associated Bone Defects.

Bone metastasis occurs in about 70% of breast cancer patients. The surgical resection of metastatic tumors often leads to bone erosion and destruction, which greatly hinders the treatment and prognosis of breast cancer patients with bone metastasis. Herein, a bifunctional scaffold 3D-printed from nanoink is fabricated to simultaneously eliminate the tumor cells and repair the tumor-associated bone defects. The metallic polydopamine (PDA) nanoparticles (FeMg-NPs) may effectively load and sustainably release the metal ions Fe3+ and Mg2+ in situ. Fe3+ exerts a chemodynamic therapy to synergize with the photothermal therapy induced by PDA with effective photothermal conversion under NIR laser, which efficiently eliminates the bone-metastatic tumor. Meanwhile, the sustained release of osteoinductive Mg2+ from the bony porous 3D scaffold enhances the new bone formation in the bone defects. Taken together, the implantation of scaffold (FeMg-SC) 3D-printed from the FeMg-NPs-containing nanoink provides a novel strategy to simultaneously eradicate bone-metastatic tumor and repair the tumor-associated bone defects.

Safety and efficacy of avapritinib in advanced systemic mastocytosis: the phase 1 EXPLORER trial.

Advanced systemic mastocytosis (AdvSM) is a rare hematologic neoplasm driven by the KIT D816V mutation and associated with poor survival. This phase 1 study ( NCT02561988 ) evaluated avapritinib (BLU-285), a selective KIT D816V inhibitor, in patients with AdvSM. The primary endpoints were the maximum tolerated dose, recommended phase 2 dose and safety of avapritinib. Secondary endpoints included overall response rate and changes in measures of mast cell burden. Avapritinib was evaluated at doses of 30-400 mg once daily in 86 patients, 69 with centrally confirmed AdvSM. Maximum tolerated dose was not reached, and 200 mg and 300 mg daily were studied in dose-expansion cohorts. The most frequent adverse events observed were periorbital edema (69%), anemia (55%), diarrhea (45%), thrombocytopenia (44%) and nausea (44%). Intracranial bleeding occurred in 13% overall, but in only 1% of patients without severe thrombocytopenia (platelets <50 × 109/l). In 53 response-evaluable patients, the overall response rate was 75%. The complete remission rate was 36%. Avapritinib elicited ≥50% reductions in marrow mast cells and serum tryptase in 92% and 99% of patients, respectively. Avapritinib induced deep and durable responses, including molecular remission of KIT D816V in patients with AdvSM, and was well tolerated at the recommended phase 2 dose of 200 mg daily.