Macrophage membrane-camouflaged nanoclusters of ultrasmall iron oxide nanoparticles for precision glioma theranostics.

Developing effective nanomedicines to cross the blood-brain barrier (BBB) for efficient glioma theranostics is still considered to be a challenging task. Here, we describe the development of macrophage membrane (MM)-coated nanoclusters (NCs) of ultrasmall iron oxide nanoparticles (USIO NPs) with dual pH- and reactive oxygen species (ROS)-responsivenesses for magnetic resonance (MR) imaging and chemotherapy/chemodynamic therapy (CDT) of orthotopic glioma. Surface citrate-stabilized USIO NPs were solvothermally synthesized, sequentially modified with ethylenediamine and phenylboronic acid, and cross-linked with gossypol to form gossypol-USIO NCs (G-USIO NCs), which were further coated with MMs. The prepared MM-coated G-USIO NCs (G-USIO@MM NCs) with a mean size of 99.9 nm display tumor microenvironment (TME)-responsive gossypol and Fe release to promote intracellular ROS production and glutathione consumption. With the MM-mediated BBB crossing and glioma targeting, the G-USIO@MM NCs can specifically inhibit orthotopic glioma in vivo through the gossypol-mediated chemotherapy and Fe-mediated CDT. Meanwhile, USIO NPs can be dissociated from the NCs under the TME, thus allowing for effective T1-weighted glioma MR imaging. The developed G-USIO@MM NCs with simple components and drug as a crosslinker are promising for glioma theranostics, and may be extended to tackle other cancer types.

GLI1 Coamplification in Well-Differentiated/Dedifferentiated Liposarcomas: Clinicopathologic and Molecular Analysis of 92 Cases.

GLI1(12q13.3) amplification is identified in a subset of mesenchymal neoplasms with a distinct nested round cell/epithelioid phenotype. MDM2 and CDK4 genes are situated along the oncogenic 12q13-15 segment, amplification of which defines well-differentiated liposarcoma (WDLPS)/dedifferentiated liposarcoma (DDLPS). The 12q amplicon can occasionally include GLI1, a gene in close proximity to CDK4. We hereby describe the first cohort of GLI1/MDM2/CDK4 coamplified WD/DDLPS. The departmental database was queried retrospectively for all cases of WD/DDLPS having undergone next-generation (MSK-IMPACT) sequencing with confirmed MDM2, CDK4, and GLI1 coamplification. Clinicopathologic data was obtained from a review of the medical chart and available histologic material. Four hundred eighty-six WD/DDLPS cases underwent DNA sequencing, 92 (19%) of which harbored amplification of the GLI1 locus in addition to that of MDM2 and CDK4. These included primary tumors (n = 60), local recurrences (n = 29), and metastases (n = 3). Primary tumors were most frequently retroperitoneal (47/60, 78%), mediastinal (4/60, 7%), and paratesticular (3/60, 5%). Average age was 63 years, with a male:female ratio of 3:2. The cohort was comprised of DDLPS (86/92 [93%], 6 of which were WDLPS with early dedifferentiation) and WDLPS without any longitudinal evidence of dedifferentiation (6/92, 7%). One-fifth (13/86, 17%) of DDLPS cases showed no evidence of a well-differentiated component in any of the primary, recurrent, or metastatic specimens. Dedifferentiated areas mostly showed high-grade undifferentiated pleomorphic sarcoma-like (26/86,30%) and high-grade myxofibrosarcoma-like (13/86,16%) morphologies. A disproportionately increased incidence of meningothelial whorls with/without osseous metaplasia was observed as the predominant pattern in 16/86 (19%) cases, and GLI1-altered morphology as described was identified in a total of 10/86 (12%) tumors. JUN (1p32.1), also implicated in the pathogenesis of WD/DDLPS, was coamplified with all 3 of MDM2, CDK4, and GLI1 in 7/91 (8%) cases. Additional loci along chromosomal arms 1p and 6q, including TNFAIP3, LATS1, and ESR1, were also amplified in a subset of cases. In this large-scale cohort of GLI1 coamplified WD/DDLPS, we elucidate uniquely recurrent features including meningothelial whorl-like and GLI-altered morphology in dedifferentiated areas. Assessment of tumor location (retroperitoneal or mediastinal), identification of a well-differentiated liposarcoma component, and coamplification of other spatially discrete genomic segments (1p and 6q) might aid in distinction from tumors with true driver GLI1 alterations.

Cell Membrane-Camouflaged Chitosan-Polypyrrole Nanogels Co-Deliver Drug and Gene for Targeted Chemotherapy and Bone Metastasis Inhibition of Prostate Cancer.

The development of functional nanoplatforms to improve the chemotherapy outcome and inhibit distal cancer cell metastasis remains an extreme challenge in cancer management. In this work, a human-derived PC-3 cancer cell membrane-camouflaged chitosan-polypyrrole nanogel (CH-PPy NG) platform, which can be loaded with chemotherapeutic drug docetaxel (DTX) and RANK siRNA for targeted chemotherapy and gene silencing-mediated metastasis inhibition of late-stage prostate cancer in a mouse model, is reported. The prepared NGs with a size of 155.8 nm show good biocompatibility, pH-responsive drug release profile, and homologous targeting specificity to cancer cells, allowing for efficient and precise drug/gene co-delivery. Through in-vivo antitumor treatment in a xenografted PC-3 mouse tumor model, it is shown that such a CH-PPy NG-facilitated co-delivery system allows for effective chemotherapy to slow down the tumor growth rate, and effectively inhibits the metastasis of prostate cancer to the bone via downregulation of the RANK/RANKL signaling pathway. The created CH-Ppy NGs may be utilized as a promising platform for enhanced chemotherapy and anti-metastasis treatment of prostate cancer.

NTRK-rearranged spindle cell neoplasm: Initial observation of imaging appearance and clinicopathologic correlation.

OBJECTIVE: To explore pre-treatment imaging findings of neurotrophic tyrosine receptor kinase (NTRK)-rearranged spindle cell neoplasm, an emerging group of molecularly defined soft tissue tumors and summarize the clinical course, including TRK inhibitor therapy response. MATERIALS AND METHODS: This retrospective study included 8 women and 4 men with NTRK-rearranged spindle cell neoplasm (median age, 35.5 years, range, 0-66). Available pre-treatment MRI, CT, PET, and US imaging were reviewed. Tumor histology and the patients' clinical course were reviewed. RESULTS: Primary tumors were located within the soft tissue, lungs, kidney, and breast with soft tissue being the most prevalent site (n = 6). Pre-treatment MRI (n = 4) revealed linear hypointense signal foci and contrast enhancement in all patients with hemorrhage in half of the tumors. A tail sign (n = 1) and fluid levels (n = 1) were less frequent. Ultrasound showed well-marginated hypoechoic masses with internal flow. Primary tumors were all non-calcified on CT (4/4). Metastases were FDG-avid (4/4). Among the 8 patients who developed metastasis, 7 developed pulmonary metastases. All four patients who received NTRK inhibitor therapy showed an initial decrease in tumor size or FDG uptake. CONCLUSION: NTRK-rearranged neoplasms may occur as enhancing masses with linear hypointense signal foci on MRI and FDG avid metastases on PET. Pulmonary metastases were frequent in our study. Initial treatment response is observed in most patients.

GRM1-Rearranged Chondromyxoid Fibroma With FGF23 Expression: A Potential Pitfall in Small Biopsies.

The clinical, radiological, and histopathological features of chondromyxoid fibroma can sometimes resemble those of other benign or malignant tumors. Recently, recurrent GRM1 rearrangements have been identified in chondromyxoid fibroma, and GRM1 positivity by immunohistochemistry has emerged as a dependable surrogate marker for this molecular alteration. Phosphaturic mesenchymal tumor is a rare tumor that often exhibits overexpression of fibroblastic growth factor 23 (FGF23) through various mechanisms. In this report, we present a case of GRM1-rearranged chondromyxoid fibroma that also exhibited FGF23 expression via in situ hybridization, posing significant diagnostic challenges during workup of the initial core biopsy. We hope that this case can serve as an educational resource, shedding light on a rare diagnostic pitfall.

PDGFRß Signaling Cooperates with ß-Catenin to Modulate c-Abl and Biologic Behavior of Desmoid-Type Fibromatosis.

PURPOSE: This study sought to identify ß-catenin targets that regulate desmoid oncogenesis and determine whether external signaling pathways, particularly those inhibited by sorafenib (e.g., PDGFRß), affect these targets to alter natural history or treatment response in patients. EXPERIMENTAL DESIGN: In vitro experiments utilized primary desmoid cell lines to examine regulation of ß-catenin targets. Relevance of results was assessed in vivo using Alliance trial A091105 correlative biopsies. RESULTS: CTNNB1 knockdown inhibited hypoxia-regulated gene expression in vitro and reduced levels of HIF1α protein. ChIP-seq identified ABL1 as a ß-catenin transcriptional target that modulated HIF1α and desmoid cell proliferation. Abrogation of either CTNNB1 or HIF1A inhibited desmoid cell-induced VEGFR2 phosphorylation and tube formation in endothelial cell co-cultures. Sorafenib inhibited this activity directly but also reduced HIF1α protein expression and c-Abl activity while inhibiting PDGFRß signaling in desmoid cells. Conversely, c-Abl activity and desmoid cell proliferation were positively regulated by PDGF-BB. Reduction in PDGFRß and c-Abl phosphorylation was commonly observed in biopsy samples from patients after treatment with sorafenib; markers of PDGFRß/c-Abl pathway activation in baseline samples were associated with tumor progression in patients on the placebo arm and response to sorafenib in patients receiving treatment. CONCLUSIONS: The ß-catenin transcriptional target ABL1 is necessary for proliferation and maintenance of HIF1α in desmoid cells. Regulation of c-Abl activity by PDGF signaling and targeted therapies modulates desmoid cell proliferation, thereby suggesting a reason for variable biologic behavior between tumors, a mechanism for sorafenib activity in desmoids, and markers predictive of outcome in patients.

Untying the Gordian knot of composite hemangioendothelioma: Discovery of novel fusions.

Composite hemangioendothelioma is a rare, locally aggressive, and rarely metastasizing vascular neoplasm which affects both children and adults. Recently, a number of gene fusions including YAP1::MAML2, PTBP1::MAML2, and EPC1::PHC2 have been detected in a small subset of cases with or without neuroendocrine expression. Herein, we present four additional cases with novel in-frame fusions. The cohort comprises two females and two males with a wide age range at diagnosis (24-80 years). Two tumors were deep involving the right brachial plexus and mediastinum, while the remaining were superficial (right plantar foot and abdominal wall). The size ranged from 1.5 to 4.8 cm in greatest dimension. Morphologically, all tumors had an admixture of at least two architectural patterns including retiform hemangioendothelioma, hemangioma, epithelioid hemangioendothelioma, or angiosarcoma. The tumors were positive for endothelial markers CD31 (3/3), ERG (4/4), and D2-40 (1/4, focal), while SMA was expressed in 2/3 highlighting the surrounding pericytes. Synaptophysin showed immunoreactivity in 2/3 cases. One patient had a local recurrence after 40 months, while two patients had no evidence of disease 4 months post-resection. Targeted RNA sequencing detected novel in-frame fusions in each of the cases: HSPG2::FGFR1, YAP1::FOXR1, ACTB::MAML2, and ARID1B::MAML2. The two cases with neuroendocrine expression occurred as superficial lesions and harbored YAP1::FOXR1 and ARID1B::MAML2 fusions. Our study expands on the molecular spectrum of this enigmatic tumor, further enhancing our current understanding of the disease.

Establishment and inactivation of mono-species biofilm in a semipilot-scale water distribution system using nanocomposite of silver nanoparticles/montmorillonite loaded cationic chitosan.

This study presents a novel approach in the synthesis and characterization of nanocomposites comprising cationic chitosan (CCS) blended with varying concentrations of silver nanoparticles/montmorillonite (AgNPs/MMT). AgNPs/MMT was synthesized using soluble starch as a reducing and stabilizing agent. Subsequently, nanocomposites, namely CCS/AgMMT-0, CCS/AgMMT-0.5, CCS/AgMMT-1.5, and CCS/AgMMT-2.5, were developed by blending 2.5 g of CCS with 0, 0.5, 1.5, and 2.5 g of AgNPs/MMT, respectively, and the corresponding nanocomposites were prepared using ball milling technique. Transmission electron microscopy (TEM) analysis revealed the formation of nanocomposites that exhibiting nearly spherical morphologies. Dynamic light scattering (DLS) measurements displayed average particle sizes of 1183 nm, 131 nm, 140 nm, and 188 nm for CCS/AgMMT-0, CCS/AgMMT-0.5, CCS/AgMMT-1.5, and CCS/AgMMT-2.5, respectively. The narrow polydispersity index (~0.5) indicated uniform particle size distributions across the nanocomposites, affirming monodispersity. Moreover, the zeta potential values exceeding 30 mV across all nanocomposites that confirmed their stability against agglomeration. Notably, CCS/AgMMT-2.5 nanocomposite exhibited potent antibacterial and antibiofilm properties against diverse pipeline materials. Findings showed that after 15 days of incubation, the highest populations of biofilm cells, Pseudomonas aeruginosa biofilm, developed over UPVC, MDPE, DCI, and SS, with corresponding HPCs of 4.79, 6.38, 8.81, and 7.24 CFU/cm2. The highest cell densities of Enterococcus faecalis biofilm in the identical situation were 4.19, 5.89, 8.12, and 6.9 CFU/cm2. The nanocomposite CCS/AgMMT-2.5 exhibited the largest measured zone of inhibition (ZOI) against both P. aeruginosa and E. faecalis, with measured ZOI values of 19 ± 0.65 and 17 ± 0.21 mm, respectively. Remarkably, the research indicates that the youngest biofilm exhibited the most notable rate of inactivation when exposed to a dose of 150 mg/L, in comparison to the mature biofilm. These such informative findings could offer valuable insights into the development of effective antibiofilm agents and materials applicable in diverse sectors such as water treatment facilities, medical devices, and industrial pipelines.

Chordoma arising from the coccygeal disc and mimicking a pilonidal cyst.

Chordomas are rare, low-grade malignant tumors often found in the sacrococcygeal region and prone to local recurrence. We report an atypical presentation of a 40-year-old patient with a symptomatic midline retrococcygeal lesion that was presumptively treated as a pilonidal cyst due to its clinical and imaging features. After surgical pathology rendered the diagnosis of chordoma, the patient required salvage surgery in the form of partial sacrectomy with soft tissue flap coverage. In addition to the unusually predominant retrococcygeal location, surgical pathology identified an intervertebral disc origin rather than the typical osseous origin. To our knowledge, this presentation of chordoma with coccygeal intervertebral origin and a large subcutaneous mass at imaging has rarely been reported in the literature. We describe this case to raise awareness of atypical presentations of sacrococcygeal chordoma that may lead to erroneous presumptive diagnosis and treatment.

Recommendations for Cell-Free DNA Assay Validations: A Joint Consensus Recommendation of the Association for Molecular Pathology and College of American Pathologists.

Diagnosing, selecting therapy for, and monitoring cancer in patients using a minimally invasive blood test represents a significant advance in precision medicine. Wide variability exists in how circulating tumor DNA (ctDNA) assays are developed, validated, and reported in the literature, which hinders clinical adoption and may negatively impact patient care. Standardization is needed for factors affecting ctDNA assay performance and reporting, including pre-analytical variables, analytical considerations, and elements of laboratory assay reporting. The Association for Molecular Pathology Clinical Practice Committee's Liquid Biopsy Working Group (LBxWG), including organizational representation from the American Society of Clinical Oncology and the College of American Pathologists, has undertaken a full-text data extraction of 1228 ctDNA publications that describe assays performed in patients with lymphoma and solid tumor malignancies. With an emphasis on clinical assay validation, the LBxWG has developed a set of 13 best practice consensus recommendations for validating, reporting, and publishing clinical ctDNA assays. Recommendations include reporting key pre-analytical considerations and assay performance metrics; this analysis demonstrates these elements are inconsistently included in publications. The LBxWG recommendations are intended to assist clinical laboratories with validating and reporting ctDNA assays and to ensure high-quality data are included in publications. It is expected that these recommendations will need to be updated as the body of literature continues to mature.

Subclonal Somatic Copy-Number Alterations Emerge and Dominate in Recurrent Osteosarcoma.

Multiple large-scale genomic profiling efforts have been undertaken in osteosarcoma to define the genomic drivers of tumorigenesis, therapeutic response, and disease recurrence. The spatial and temporal intratumor heterogeneity could also play a role in promoting tumor growth and treatment resistance. We conducted longitudinal whole-genome sequencing of 37 tumor samples from 8 patients with relapsed or refractory osteosarcoma. Each patient had at least one sample from a primary site and a metastatic or relapse site. Subclonal copy-number alterations were identified in all patients except one. In 5 patients, subclones from the primary tumor emerged and dominated at subsequent relapses. MYC gain/amplification was enriched in the treatment-resistant clones in 6 of 7 patients with multiple clones. Amplifications in other potential driver genes, such as CCNE1, RAD21, VEGFA, and IGF1R, were also observed in the resistant copy-number clones. A chromosomal duplication timing analysis revealed that complex genomic rearrangements typically occurred prior to diagnosis, supporting a macroevolutionary model of evolution, where a large number of genomic aberrations are acquired over a short period of time followed by clonal selection, as opposed to ongoing evolution. A mutational signature analysis of recurrent tumors revealed that homologous repair deficiency (HRD)-related SBS3 increases at each time point in patients with recurrent disease, suggesting that HRD continues to be an active mutagenic process after diagnosis. Overall, by examining the clonal relationships between temporally and spatially separated samples from patients with relapsed/refractory osteosarcoma, this study sheds light on the intratumor heterogeneity and potential drivers of treatment resistance in this disease. SIGNIFICANCE: The chemoresistant population in recurrent osteosarcoma is subclonal at diagnosis, emerges at the time of primary resection due to selective pressure from neoadjuvant chemotherapy, and is characterized by unique oncogenic amplifications.

Digital pathology operations at a tertiary cancer center: Infrastructure requirements and operational cost.

Whole slide imaging is revolutionizing the field of pathology and is currently being used for clinical, educational, and research initiatives by an increasing number of institutions. Pathology departments have distinct needs for digital pathology systems, yet the cost of digital workflows is cited as a major barrier for widespread adoption by many organizations. Memorial Sloan Kettering Cancer Center (MSK) is an early adopter of whole slide imaging with incremental investments in resources that started more than 15 years ago. This experience and the large-scale scan operations led to the identification of required framework components of digital pathology operations. The cost of these components for the 2021 digital pathology operations at MSK were studied and calculated to enable an understanding of the operation and benchmark the accompanying costs. This paper describes the unique infrastructure cost and the costs associated with the digital pathology clinical operation use cases in a large, tertiary cancer center. These calculations can serve as a blueprint for other institutions to provide the necessary concepts and offer insights towards the financial requirements for digital pathology adoption by other institutions.

Quality Management System in Clinical Digital Pathology Operations at a Tertiary Cancer Center.

Digital pathology workflows can improve pathology operations by allowing reliable and fast retrieval of digital images, digitally reviewing pathology slides, enabling remote work and telepathology, use of computer-aided tools, and sharing of digital images for research and educational purposes. The need for quality systems is a prerequisite for successful clinical-grade digital pathology adoption and patient safety. In this article, we describe the development of a structured digital pathology laboratory quality management system (QMS) for clinical digital pathology operations at Memorial Sloan Kettering Cancer Center (MSK). This digital pathology-specific QMS development stemmed from the gaps that were identified when MSK integrated digital pathology into its clinical practice. The digital scan team in conjunction with the Department of Pathology and Laboratory Medicine quality team developed a QMS tailored to the scanning operation to support departmental and institutional needs. As a first step, systemic mapping of the digital pathology operations identified the prescan, scan, and postscan processes; instrumentation; and staffing involved in the digital pathology operation. Next, gaps identified in quality control and quality assurance measures led to the development of standard operating procedures and training material for the different roles and workflows in the process. All digital pathology-related documents were subject to regulatory review and approval by departmental leadership. The quality essentials were developed into an extensive Digital Pathology Quality Essentials framework to specifically address the needs of the growing clinical use of digital pathology technologies. Using the unique digital experience gained at MSK, we present our recommendations for QMS for large-scale digital pathology operations in clinical settings.

RNA Sequencing for Solid Tumor Fusion Gene Detection: Proficiency Testing Practice and Performance Comparison.

CONTEXT.­: Next-generation sequencing-based approaches using RNA have increasingly been used by clinical laboratories for the detection of fusion genes, intragenic rearrangements, and exon-skipping events. Correspondingly, the College of American Pathologists (CAP) has advanced RNA sequencing proficiency testing (PT) to ensure optimal performance of these assays. OBJECTIVE.­: To report on laboratory performance and practices of RNA sequencing for the detection of fusion genes, intragenic rearrangements, and exon-skipping events using CAP PT data from 8 mailings (2018-A through 2021-B). DESIGN.­: CAP PT RNA sequencing program results from 153 laboratories across 24 proficiency test specimens, interrogating 22 distinct engineered fusion transcripts, were analyzed for correct identification of the fusion event, associated performance variables, and laboratory practices. RESULTS.­: Overall, the 4-year program detection rate (sensitivity) was 95.5% (1486 of 1556 results). False-negative rates were 3.6% (53 of 1463) and 18.3% (17 of 93) for fusion gene and intragenic rearrangement/exon-skipping events, respectively. Only 19 false-positive results were reported among the 8 PT mailings, and most were likely the result of preanalytical or postanalytical errors. There were no practice characteristics (eg, instrumentation, sequencing method) significantly associated with the fusion detection results. CONCLUSIONS.­: These data reveal a high overall sensitivity and specificity for fusion gene detection by participating laboratories using clinical RNA sequencing. Performance was comparable across all laboratories, regardless of methodology. The fraction of false-negative results for intragenic rearrangement/exon-skipping events was greater than that for the chimeric fusion genes. False-negative results could not be attributed to any specific practice characteristics.

Dual-mode security authentication of SrAl2 O4 :Eu,Dy phosphor encapsulated in electrospun cellulose acetate nanofibrous films.

Photochromic inks have been an attractive authentication strategy to improve the anti-counterfeiting efficiency of commercial products. However, recent reports have shown significant disadvantages with photochromic inks, including poor durability and high cost. In this context, we developed novel photochromic nanofibres for advanced anti-counterfeiting applications. Lanthanide-doped strontium aluminate (LdSA) nanoparticles (NPs) were prepared and immobilized into electrospun cellulose acetate nanofibres (CANF). Authentication materials immobilized with inorganic photochromic agents can warranty durability and photostability. Therefore, the ultraviolet-stimulated photochromism of LdSA-encapsulated cellulose acetate nanofibres (LdSA@CANF) demonstrated high reversibility and photostability. A broad range of cellulose acetate nanofibres with unique emission characteristics was developed when applying different ratios of LdSA NPs. LdSA@CANF appeared colourless under visible daylight, whereas a green emission was monitored under ultraviolet-light illumination. The shape and chemical content of the photochromic fibrous films were examined using various analytical techniques. The mechanical characteristics of LdSA@CANF-coated paper were investigated. The emission wavelength was detected at 514 nm to designate green colour, whereas the excitation wavelength was detected at 369 nm to indicate transparency. The prepared cellulose acetate nanofibrous film can be described as an efficient strategy for the anti-counterfeiting of commercialized items.

Photoluminescent polymer-based smart window reinforced with electrospun glass nanofibres.

Poly(vinyl chloride) (PVC) was reinforced with electrospun glass nanofibres (EGN) to develop photochromic and afterglow materials such as smart windows and anti-counterfeiting prints. A colourless electrospun glass nanofibres@poly(vinyl chloride) (EGN@PVC) sheet was prepared by physical integration of lanthanide-doped aluminate nanoparticles (LANP). The low concentrations of LANP in the photochromic and photoluminescent EGN@PVC hybrids displayed fluorescence emission with instant reversibility. EGN@PVC with the highest phosphor concentrations showed persistent phosphorescence emission with slow reversibility. Based on the results of the Commission Internationale de l'éclairage Laboratory and luminescence spectroscopy, the translucent EGN@PVC samples became green in the presence of ultraviolet illumination and greenish-yellow in the absence of light. According to scanning electron microscopy (SEM) and transmission electron microscopy (TEM) analyses, the morphological study of EGN and LANP showed diameters of 75-95 and 11-19 nm, respectively. The morphology of the EGN@PVC substrates was studied using SEM, X-ray fluorescence, and energy-dispersive X-ray spectroscopy. The mechanical characteristics of PVC were enhanced by reinforcement with EGN as a roughening agent. When comparing the scratching resistance of LANP-free substrate to photoluminescent EGN@PVC substrates, it was observed that the latter was much superior. The photoluminescence spectra were reported to have an emission peak at 519 nm when excited at 365 nm. These findings demonstrated that the luminous transparent EGN@PVC composites had improved superhydrophobic and UV-blocking characteristics.

Fabrication and Characterization of Eco-Friendly Thin Films as Potential Optical Absorbers for Efficient Multi-Functional Opto-(Electronic) and Solar Cell Applications.

The necessity for reliable and efficient multifunctional optical and optoelectronic devices is always calling for the exploration of new fertile materials for this purpose. This study leverages the exploitation of dyed environmentally friendly biopolymeric thin films as a potential optical absorber in the development of multifunctional opto-(electronic) and solar cell applications. Uniform, stable thin films of dyed chitosan were prepared using a spin-coating approach. The molecular interactivity between the chitosan matrix and all the additive organic dyes was evaluated using FTIR measurements. The color variations were assessed using chromaticity (CIE) measurements. The optical properties of films were inspected using the measured UV-vis-NIR transmission and reflection spectra. The values of the energy gap and Urbach energy as well as the electronic parameters and nonlinear optical parameters of films were estimated. The prepared films were exploited for laser shielding as an attenuated laser cut-off material. In addition, the performance of the prepared thin films as an absorbing organic layer with silicon in an organic/inorganic heterojunction architecture for photosensing and solar energy conversion applicability was studied. The current-voltage relation under dark and illumination declared the suitability of this architecture in terms of responsivity and specific detectivity values for efficient light sensing applications. The suitability of such films for solar cell fabrications is due to some dyed films achieving open-circuit voltage and short-circuit current values, where Saf-dyed films achieved the highest Voc (302 mV) while MV-dyed films achieved the highest Jsc (0.005 mA/cm2). Finally, based on all the obtained characterization results, the engineered natural cost-effective dyed films are considered potential active materials for a wide range of optical and optoelectronic applications.

Distinct IDH1/2-associated Methylation Profile and Enrichment of TP53 and TERT Mutations Distinguish Dedifferentiated Chondrosarcoma from Conventional Chondrosarcoma.

Dedifferentiated chondrosarcoma (DDCS) is a rare high-grade chondrosarcoma characterized by a well-differentiated chondrosarcoma (WDCS) component that abruptly transitions to a high-grade, noncartilaginous sarcomatous component. To date, the molecular pathogenesis of DDCS and its distinction from conventional chondrosarcoma remain poorly understood. By targeted sequencing, we examined the mutational and copy-number profiles of 18 DDCS, including macrodissected WDCS components, compared with 55 clinically sequenced conventional chondrosarcomas. In conjunction with publicly available external data, we analyzed the methylation and expression profiles of 34 DDCS and 94 conventional chondrosarcomas. Isocitrate dehydrogenase 1/isocitrate dehydrogenase 2 (IDH1/IDH2) mutations were present in 36% conventional chondrosarcomas and 71% DDCS. Compared with conventional chondrosarcomas, DDCS had higher frequencies of TP53 and TERT promoter mutations and CDKN2A/B copy-number losses. Paired analysis of macrodissected WDCS and the high-grade components revealed TERT promoter mutations as early events. Despite phenotypic similarities, the percentage of genome with copy-number alterations in DDCS was significantly lower than that in other high-grade sarcomas. Differential methylation analysis revealed reduction of IDH1/IDH2-associated global hypermethylation characteristically seen in conventional chondrosarcoma and a distinct methylation profile in DDCS. The WDCS and high-grade components in DDCS showed similar methylation profiles. These CpG sites were associated with upregulated expression of genes involved in G2-M checkpoints and E2F targets. Genomic profiling revealed enrichment of TP53, TERT promoter, and CDKN2A/B alterations in DDCS. Integrated methylation and gene expression analysis revealed distinct IDH1/IDH2-associated methylation and transcriptional profiles as early events in DDCS, which may underlie the pathogenesis of dedifferentiation in chondrosarcomas. Significance: DDCS is a rare, high-grade chondrosarcoma with a dismal prognosis. About 50%-80% of DDCS harbor IDH1/IDH2 mutations. We uncover a significant alteration of IDH-associated methylation profile in DDCS, which we propose is key to the progression to dedifferentiation. In this context, the potential effect of the use of IDH inhibitors is unclear but important to address, as clinical trials of selective IDH1 inhibitors showed worse outcome in DDCS.

Molten Salts Approach of Poly(vinyl alcohol)-Derived Bimetallic Nickel-Iron Sheets Supported on Porous Carbon Nanosheet as an Effective and Durable Electrocatalyst for Methanol Oxidation.

The preparation of metallic nanostructures supported on porous carbon materials that are facile, green, efficient, and low-cost is desirable to reduce the cost of electrocatalysts, as well as reduce environmental pollutants. In this study, a series of bimetallic nickel-iron sheets supported on porous carbon nanosheet (NiFe@PCNs) electrocatalysts were synthesized by molten salt synthesis without using any organic solvent or surfactant through controlled metal precursors. The as-prepared NiFe@PCNs were characterized by scanning and transmission electron microscopy (SEM and TEM), X-ray diffraction, and photoelectron spectroscopy (XRD and XPS). The TEM results indicated the growth of NiFe sheets on porous carbon nanosheets. The XRD analysis confirmed that the Ni1-xFex alloy had a face-centered polycrystalline (fcc) structure with particle sizes ranging from 15.5 to 30.6 nm. The electrochemical tests showed that the catalytic activity and stability were highly dependent on the iron content. The electrocatalytic activity of catalysts for methanol oxidation demonstrated a nonlinear relationship with the iron ratio. The catalyst doped with 10% iron showed a higher activity compared to the pure nickel catalyst. The maximum current density of Ni0.9Fe0.1@PCNs (Ni/Fe ratio 9:1) was 190 mA/cm2 at 1.0 M of methanol. In addition to the high electroactivity, the Ni0.9Fe0.1@PCNs showed great improvement in stability over 1000 s at 0.5 V with a retained activity of 97%. This method can be used to prepare various bimetallic sheets supported on porous carbon nanosheet electrocatalysts.