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One of the difficulties limiting covalent organic frameworks (COFs) from becoming excellent adsorbents is their stacking/aggregation architectures owing to poor morphology/structure control during the synthesis process. Herein, an inorganic-organic nanoarchitectonics strategy to synthesize the MXene/COF heterostructure (Ti3 C2 Tx /TAPT-TFP) is developed by the assembly of ß-ketoenamine-linked COF on the Ti3 C2 Tx MXene nanosheets. The as-prepared Ti3 C2 Tx /TAPT-TFP retains the 2D architecture and high adsorption capacity of MXenes as well as large specific surface area and hierarchical porous structure of COFs. As a proof of concept, the potential of Ti3 C2 Tx /TAPT-TFP for solid-phase microextraction (SPME) of trace organochlorine pesticides (OCPs) is investigated. The Ti3 C2 Tx /TAPT-TFP based SPME method achieves low limits of detection (0.036-0.126 ng g-1 ), wide linearity ranges (0.12-20.0 ng g-1 ), and acceptable repeatabilities for preconcentrating trace OCPs from fruit and vegetable samples. This study offers insights into the potential of constructing COF or MXene-based heterostructures for the microextraction of environmental pollutants.
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MAIN CONCLUSION: A mutation was first found to cause the great generation of glutelin precursors (proglutelins) in rice (Oryza sativa L.) endosperm, and thus referred to as GPGG1. The GPGG1 was involved in synthesis and compartmentation of storage proteins. The PPR-like gene in GPGG1-mapped region was determined as its candidate gene. In the wild type rice, glutelins and prolamins are synthesized on respective subdomains of rough endoplasmic reticulum (ER) and intracellularly compartmentalized into different storage protein bodies. In this study, a storage protein mutant was obtained and characterized by the great generation of proglutelins combining with the lacking of 13 kD prolamins. A dominant genic-mutation, referred to as GPGG1, was clarified to result in the proteinous alteration. Novel saccular composite-ER was shown to act in the synthesis of proglutelins and 14 kD prolamins in the mutant. Additionally, a series of organelles including newly occurring several compartments were shown to function in the transfer, trans-plasmalemmal transport, delivery, deposition and degradation of storage proteins in the mutant. The GPGG1 gene was mapped to a 67.256 kb region of chromosome 12, the pentatricopeptide repeat (PPR)-like gene in this region was detected to contain mutational sites.
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Endosperma , Glutens , Mutação , Oryza , Oryza/genética , Oryza/metabolismo , Endosperma/genética , Endosperma/metabolismo , Glutens/genética , Glutens/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Prolaminas/genética , Prolaminas/metabolismo , Proteínas de Armazenamento de Sementes/genética , Proteínas de Armazenamento de Sementes/metabolismo , Retículo Endoplasmático/metabolismo , Mapeamento Cromossômico , Genoma de Planta/genéticaRESUMO
Lithium-sulfur batteries (LiSBs) with high energy density still face challenges on sluggish conversion kinetics, severe shuttle effects of lithium polysulfides (LiPSs), and low blocking feature of ordinary separators to LiPSs. To tackle these, a novel double-layer strategy to functionalize separators is proposed, which consists of Co with atomically dispersed CoN4 decorated on Ketjen black (Co/CoN4@KB) layer and an ultrathin 2D Ti3C2Tx MXene layer. The theoretical calculations and experimental results jointly demonstrate metallic Co sites provide efficient adsorption and catalytic capability for long-chain LiPSs, while CoN4 active sites facilitate the absorption of short-chain LiPSs and promote the conversion to Li2S. The stacking MXene layer serves as a microscopic barrier to further physically block and chemically anchor leaked LiPSs from the pores and gaps of the Co/CoN4@KB layer, thus preserving LiPSs within efficient anchoring-conversion reaction interfaces to balance the accumulation of "dead S" and Li2S. Consequently, with an ultralight loading of Co/CoN4@KB-MXene, the LiSBs exhibit amazing electrochemical performance even under high sulfur loading and lean electrolyte, and the outperforming performance for lithium-selenium batteries (LiSeBs) can also be achieved. This work exploits a universal and effective strategy of a double-layer functionalized separator to regulate the equilibrium adsorption-catalytic interface, enabling high-energy and long-cycle LiSBs/LiSeBs.
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Iron-based mixed polyanion phosphate Na4Fe3(PO4)2P2O7 (NFPP) is recognized as a promising cathode for Sodium-ion Batteries (SIBs) due to its low cost and environmental friendliness. However, its inherent low conductivity and sluggish Na+ diffusion limit fast charge and low-temperature sodium storage. This study pioneers a scalable synthesis of hollow core-shelled Na4Fe2.4Ni0.6(PO4)2P2O7 with tiny-void space (THoCS-0.6Ni) via a one-step spray-drying combined with calcination process due to the different viscosity, coordination ability, molar ratios, and shrinkage rates between citric acid and polyvinylpyrrolidone. This unique structure with interconnected carbon networks ensures rapid electron transport and fast Na+ diffusion, as well as efficient space utilization for relieving volume expansion. Incorporating regulation of lattice structure by doping Ni heteroatom to effectively improve intrinsic electron conductivity and optimize Na+ diffusion path and energy barrier, which achieves fast charge and low-temperature sodium storage. As a result, THoCS-0.6Ni exhibits superior rate capability (86.4â mAh g-1 at 25â C). Notably, THoCS-0.6Ni demonstrates exceptional cycling stability at -20 °C with a capacity of 43.6â mAh g-1 after 2500â cycles at 5â C. This work provides a universal strategy to design the hollow core-shelled structure with tiny-void space cathode materials for reversible batteries with fast-charge and low-temperature Na-storage features.
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Low Na+ and electron diffusion kinetics severely restrain the rate capability of MoS2 as anode for sodium-ion batteries (SIBs). Slow phase transitions between 2H and 1T, and from NaxMoS2 to Mo and Na2S as well as the volume change during cycling, induce a poor cycling stability. Herein, an original Fe single atom doped MoS2 hollow multishelled structure (HoMS) is designed for the first time to address the above challenges. The Fe single atom in MoS2 promotes the electron transfer, companying with shortened charge diffusion path from unique HoMS, thereby achieving excellent rate capability. The strong adsorption with Na+ and self-catalysis of Fe single atom facilitates the reversible conversion between 2H and 1T, and from NaxMoS2 to Mo and Na2S. Moreover, the buffering effect of HoMS on volume change during cycling improves the cyclic stability. Consequently, the Fe single atom doped MoS2 quadruple-shelled sphere exhibits a high specific capacity of 213.3â mAh g-1 at an ultrahigh current density of 30â A g-1, which is superior to previously-reported results. Even at 5â A g-1, 259.4â mAh g-1 (83.68 %) was reserved after 500 cycles. Such elaborate catalytic site decorated HoMS is also promising to realize other "fast-charging" high-energy-density rechargeable batteries.
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Although cobalt (Co) is indispensable for life, it is toxic to cells when accumulated in excess. The DmeRF system is a well-characterized metal-response system that contributes to Co and nickel resistance in certain bacterial species. The Vibrio parahaemolyticus RIMD 2210633 genome also harbors a dmeRF operon that encodes a multiple antibiotic resistance regulator family transcriptional regulator and a cation diffusion facilitator family protein. Quantitative real-time PCR, growth curves analysis, inductively coupled plasma-mass spectrometry, ß-galactosidase activity assays, electrophoretic mobility shift assays, and a mouse infection experiment were performed to characterize the function of the DmeRF system in V. parahaemolyticus. Zinc, copper, and Co significantly increase dmeF expression, with Co inducing the greatest increase. DmeF promotes V. parahaemolyticus growth under high-Co conditions. Additionally, increased accumulation of cellular Co in the ΔdmeF mutant indicates that DmeF is potentially involved in Co efflux. Moreover, DmeR represses the dmeRF operon by binding directly to its promoter in the absence of Co. Finally, the DmeRF system was not required for V. parahaemolyticus virulence in mice. Collectively, our data indicate that the DmeRF system is involved in maintaining Co homeostasis in V. parahaemolyticus and DmeR functioning as a repressor of the operon.
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Vibrio parahaemolyticus , Animais , Camundongos , Vibrio parahaemolyticus/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Cobalto/metabolismo , HomeostaseRESUMO
Multi-wall Sn/SnO2 @carbon hollow nanofibers evolved from SnO2 nanofibers are designed and programable synthesized by electrospinning, polypyrrole coating, and annealing reduction. The synthesized hollow nanofibers have a special wire-in-double-wall-tube structure with larger specific surface area and abundant inner spaces, which can provide effective contacting area of electrolyte with electrode materials and more active sites for redox reaction. It shows excellent cycling stability by virtue of effectively alleviating pulverization of tin-based electrode materials caused by volume expansion. Even after 2000 cycles, the wire-in-double-wall-tube Sn/SnO2 @carbon nanofibers exhibit a high specific capacity of 986.3â mAh g-1 (1â A g-1 ) and still maintains 508.2â mAh g-1 at high current density of 5â A g-1 . This outstanding electrochemical performance suggests the multi-wall Sn/SnO2 @ carbon hollow nanofibers are great promising for high performance energy storage systems.
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Precisely carving of multi-shelled manganese-cobalt oxide hollow dodecahedra (Co/Mn-HD) with shell number up to three is achieved by a controlled calcination of the Mn-doped zeolitic imidazolate framework ZIF-67 precursor (Co/Mn-ZIF). The unique multi-shelled and polycrystalline structure not only provides a very large electrochemically active surface area (EASA), but also enhances the structural stability of the material. The residual C and N in the final structures might aid stability and increase their conductivity. When used in alkaline rechargeable battery, the triple-shelled Co/Mn-HD exhibits high electrochemical performance, reversible capacity (331.94â mAh g-1 at 1â Ag-1 ), rate performance (88 % of the capacity can be retained with a 20-fold increase in current density), and cycling stability (96 % retention over 2000â cycles).
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Multishelled binary metal oxide, which can exert a synergetic effect of different oxides, is a promising electrochemical electrode material. However, it is challenging to synthesize this kind of binary metal oxide due to the severe hydrolysis and/or precipitation reactions of the precursors between cations and anions of different metals. Herein, by using citric acid as a chelating agent to inhibit hydrolysis and precipitation, a series of multishelled binary metal oxide hollow spheres (Fe2(MoO4)3, NiMoO4, MnMoO4, CoWO4, MnWO4, etc.) were obtained via coabsorption of negative and positive metal ions. In addition, the chelation between a metal ion and citric acid is systematically validated by NMR, MS, Raman, and UV-vis. In particular, multishelled Fe2(MoO4)3 hollow spheres show excellent electrochemical performance as cathode material for sodium-ion batteries benefited from their structural superiorities. Especially, the quintuple-shelled Fe2(MoO4)3 hollow sphere shows the highest specific capacity (99.03 mAh g-1) among all Fe2(MoO4)3 hollow spheres, excellent stability (85.6 mAh g-1 was retained after 100 cycles at a current density of 2.2 C), and outstanding rate capability (67.4 mAh g-1 can be obtained at a current density of 10 C). This general approach can be extended to the synthesis of other multishelled multielement metal oxides and greatly enrich the diversity of hollow multishelled structures.
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Biomarcadores Tumorais , Linfoma Plasmablástico/diagnóstico , Linfoma Plasmablástico/genética , Família de Moléculas de Sinalização da Ativação Linfocitária/genética , Biomarcadores , Humanos , Imuno-Histoquímica , Imunofenotipagem , Terapia de Alvo Molecular , Fenótipo , Linfoma Plasmablástico/tratamento farmacológico , Linfoma Plasmablástico/metabolismo , Prognóstico , Família de Moléculas de Sinalização da Ativação Linfocitária/metabolismoRESUMO
Chronic wounds with bacterial infection present formidable clinical challenges. In this study, a versatile hydrogel dressing with antibacterial and angiogenic activity composite of silk fibroin (SF), chondroitin sulfate (CS), and graphene oxide quantum dots (GOQDs) is fabricated. GOQDs@SF/CS (GSC) hydrogel is rapidly formed through the enzyme catalytic action of horseradish peroxidase. With the incorporation of GOQDs both gelation speed and mechanical properties have been enhanced, and the photothermal characteristics of GOQDs in GSC hydrogel enabled bacterial killing through photothermal treatment (PTT) at â¼51 °C. In vitro studies show that the GSC hydrogels demonstrate excellent antibacterial performance and induce type H vessel differentiation of endothelial cells via the activated ERK1/2 signaling pathway and upregulated SLIT3 expression. In vivo results show that the hydrogel significantly promotes type H vessels formation, which is related to the collagen deposition, epithelialization and, ultimately, accelerates the regeneration of infected skin defects. Collectively, this multifunctional GSC hydrogel, with dual action of antibacterial efficacy and angiogenesis promotion, emerges as an innovative skin dressing with the potential for advancing in infected wound healing.
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Fibroínas , Grafite , Pontos Quânticos , Fibroínas/farmacologia , Sulfatos de Condroitina/farmacologia , Hidrogéis/farmacologia , Células Endoteliais , Cicatrização , Antibacterianos/farmacologiaRESUMO
Background/purpose: The pathophysiology of burning mouth syndrome (BMS), although considered a multifactorial etiology including psychological factors, is still not well understood. Hence, this study aimed to investigate the potential usage of salivary and serum biomarkers, including brain-derived neurotrophic factor (BDNF), interferon-gamma (IFN-γ), interleukin-1beta (IL-1ß), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-alpha (TNF-α), in diagnosing BMS and their correlations with anxiety/depression. Materials and methods: 45 BMS patients and 14 healthy volunteers were enrolled. The patients were divided into BMS with anxiety/depression group and BMS without anxiety/depression group according to the scores of the Zung Self-rating Anxiety Scale (SAS) and Zung Self-rating Depression Scale (SDS). Additionally, concentrations of BDNF, IFN-γ, IL-1ß, IL-6, IL-8, and TNF-α in saliva and those in serum among the patients and healthy volunteers were assessed by multiplex assay using Luminex 200TM system and Enzyme-linked immunosorbent assay (ELISA), respectively. Results: Among all the serum biomarkers, only BDNF showed a statistically significant decrease in the patients than the healthy volunteers (P < 0.05). Regarding saliva biomarkers, BDNF, IL-1ß, and IL-8 all exhibited a statistically significant increase in all the BMS patients versus the healthy volunteers (P < 0.05) but only BDNF was significantly different between patients with anxiety/depression and healthy individuals when considering anxiety/depression. Among BMS patients with anxiety/depression, saliva TNF-α had positive associations with other biomarkers including BDNF, IFN-γ, IL-1ß, IL-6, and IL-8 (P < 0.05). Conclusion: The increased concentration of saliva BDNF holds strong potential for diagnosing BMS and the elevated level of saliva TNF-α is crucial in identifying BMS patients with anxiety/depression.
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The two-phase reaction of Na3 V2 (PO4 )3 - Na1 V2 (PO4 )3 in Na3 V2 (PO4 )3 (NVP) is hindered by low electronic and ionic conductivity. To address this problem, a surface-N-doped NVP encapsulating by N-doped carbon nanocage (N-NVP/N-CN) is rationally constructed, wherein the nitrogen is doped in both the surface crystal structure of NVP and carbon layer. The surface crystal modification decreases the energy barrier of Na+ diffusion from bulk to electrolyte, enhances intrinsic electronic conductivity, and releases lattice stress. Meanwhile, the porous architecture provides more active sites for redox reactions and shortens the diffusion path of ion. Furthermore, the new interphase of Na2 V2 (PO4 )3 is detected by in situ XRD and clarified by density functional theory (DFT) calculation with a lower energy barrier during the fast reversible electrochemical three-phase reaction of Na3 V2 (PO4 )3 - Na2 V2 (PO4 )3 - Na1 V2 (PO4 )3 . Therefore, as cathode of sodium-ion battery, the N-NVP/N-CN exhibited specific capacities of 119.7 and 75.3 mAh g-1 at 1 C and even 200 C. Amazingly, high capacities of 89.0, 86.2, and 84.6 mAh g-1 are achieved after overlong 10000 cycles at 20, 40, and 50 C, respectively. This approach provides a new idea for surface crystal modification to cast intermediate Na2 V2 (PO4 )3 phase for achieving excellent cycling stability and rate capability.
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Molybdenum carbide (MoC) has emerged as a promising material for capacitive deionization (CDI), but the poor electrochemical kinetics in conventional MoC owing to the bulk structure and low electric conductivity limit its CDI performance. To address this challenge, herein, we develop a novel strategy to synthesize ultrafine MoC nanocrystals that are embedded within a three-dimensional nitrogen-doped carbon framework (NC/MoC). This synthesis method involves the space-confined pyrolysis of molybdate precursors within metal-organic frameworks (MOFs). In this process, molybdates are confined into the MOF crystalline structure, where MOFs provide a confined reactor and carbon source. The resulting NC/MoC with the uniformly distributed MoC nanocrystals provides sufficient active sites for the electrosorption of salt ions, while the MOF-derived NC matrix facilitates charge transfer and provides the space-confined effect for preventing the possible aggregations of MoC nanocrystals during the CDI process. The NC/MoC exhibits an impressive salt adsorption capacity (SAC, 84.2 mg g-1, 1.2 V), rapid desalination rate, and high cycling stability (91.4% SAC retention after 200 cycles), better than those of most previously reported carbon-based CDI materials. Besides, the possible mechanisms are systematically investigated by ex situ characterization and density functional theory calculations. This study opens up new avenues for the construction of metal carbide-based nanocrystals for CDI and other electrochemical applications.
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BACKGROUND: Aggressive NK/T-Cell neoplasms are rare hematological malignancies characterized by the abnormal proliferation of NK or NK-like T (NK/T) cells. CD6 is a transmembrane signal transducing receptor involved in lymphocyte activation and differentiation. This study aimed to investigate the CD6 expression in these malignancies and explore the potential of targeting CD6 in these diseases. MATERIALS AND METHODS: We conducted a retrospective study with totally 41 cases to investigate the expression of CD6 by immunohistochemistry, including aggressive NK-cell leukemia/lymphoma (ANKLL: N = 10) and extranodal NK/T-cell lymphoma (ENKTL: N = 31). A novel ANKLL model was applied for proof-of-concept functional studies of a CD6 antibody-drug-conjugate (CD6-ADC) both in vitro and in animal trial. RESULTS: CD6 was expressed in 68.3% (28/41) of cases (70% (7/10) of ANKLL and 67.7% (21/31) of ENKTL). The median overall survival (OS) for ANKLL and ENTKL cases was 1 and 12 months, respectively, with no significant difference in OS based on CD6 expression (p > 0.05, Kaplan-Meier with log-rank test). In vitro exposure of the CCANKL cell line, derived from an ANKL patient, to an anti-CD6ADC resulted in dose dependent induction of apoptosis. Furthermore, CCANKL engraftment in NSG mice could be blocked by treatment with the anti-CD6 ADC. CONCLUSION: To date, this is the first report to explore the expression of CD6 in ANKLL and ENKTL and confirms its expression in the majority of cases. The in vitro and in vivo data support further investigation of CD6 as a potential therapeutic target in these aggressive NK/T-cell malignancies.
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Previously, we showed that inhibition of the protein kinase C ß (PKCß)/AKT pathway augments engagement of the histone deacetylase inhibitor (HDI)-induced apoptosis in lymphoma cells. In the present study, we investigated the cytotoxicity and mechanisms of cell death induced by the delta isoform-specific phosphatidylinositide 3-kinase (PI3K) inhibitor, GS-1101, in combination with the HDI, panobinostat (LBH589) and suberoylanilide hydroxamic acid (SAHA). Lymphoma cell lines, primary non-Hodgkin Lymphoma (NHL) and chronic lymphocytic leukaemia (CLL) cells were simultaneously treated with the HDI, LBH589 and GS-1101. An interaction of the LBH589/GS-1101 combination was formally examined by using various concentrations of LBH589 and GS-1101. Combined treatment resulted in a synergistic inhibition of proliferation and showed synergistic effect on apoptotic induction in all tested cell lines and primary NHL and CLL cells. This study indicates that interference with PI3K signalling dramatically increases HDI-mediated apoptosis in malignant haematopoietic cells, possibly through both AKT-dependent or AKT- independent mechanisms. Moreover, the increase in HDI-related apoptosis observed in PI3K inhibitor-treated cells appears to be related to the disruption of the extracellular signal-regulated kinase (ERK) signalling pathway. This study provides a strong rational for testing the combination of PI3K inhibitors and HDI in the clinic.
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Apoptose/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Inibidores de Histona Desacetilases/farmacologia , Inibidores de Fosfoinositídeo-3 Quinase , Purinas/farmacologia , Quinazolinonas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/toxicidade , Caspases/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sinergismo Farmacológico , Ativação Enzimática/efeitos dos fármacos , Inibidores de Histona Desacetilases/toxicidade , Humanos , Ácidos Hidroxâmicos/farmacologia , Ácidos Hidroxâmicos/toxicidade , Indóis/farmacologia , Indóis/toxicidade , Concentração Inibidora 50 , Linfoma de Células B/metabolismo , Modelos Biológicos , Panobinostat , Fosfatidilinositol 3-Quinases/metabolismo , Purinas/toxicidade , Quinazolinonas/toxicidadeRESUMO
More recently, NCAPG2 has emerged as an intrinsically essential participant of the condensin II complex involved in the process of chromosome cohesion and stabilization in mitosis, and its position in particular tumours is now being highlighted. Simultaneously, the genetic properties of NCAPG2 hint that it might have enormous potential to interpret the malignant progression of tumors in a broader perspective, that is, in pan-cancer. Yet, at present, this recognition remains merely superficial and there is a lack of more detailed studies to explore the underlying pathogenesis. To meet this need, the current study was undertaken to comprehensively elucidate the potential functions of NCAPG2 in pan-cancer, based on a combination of existing databases like TCGA and GTEx. NCAPG2 was identified to be overexpressed in almost every tumor and to exhibit significant prognostic and diagnostic efficacy. Furthermore, the correlation between NCAPG2 and selected immune features, namely immune cell infiltration, immune checkpoint genes, TMB, MSI, etc. also indicates that NCAPG2 could potentially be applied in guidance of immunotherapy. Subsequently, in pancreatic cancer, this study further clarified the utility of NCAPG2 that downregulation of its expression could result in reduced proliferation, invasion and metastasis of pancreatic cancer cells, among such phenotypical changes, the epithelial-mesenchymal transition disruption could be at least one of the possible mechanisms raising or enhancing tumorigenesis. Taken above, NCAPG2, as a member of pan-oncogenes, would serve as a biomarker and potential therapeutic target for a range of malignancies, sharing new insights into precision medicine.
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Neoplasias Pancreáticas , Humanos , Prognóstico , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genética , Oncogenes , Carcinogênese , Proteínas Cromossômicas não Histona , Neoplasias PancreáticasRESUMO
BACKGROUND: Histologic evaluation of the mucosal changes associated with celiac disease is important for establishing an accurate diagnosis and monitoring the impact of investigational therapies. While the Marsh-Oberhuber classification has been used to categorize the histologic findings into discrete stages (i.e., Type 0-3c), significant variability has been documented between observers using this ordinal scoring system. Therefore, we evaluated whether pathologist-trained machine learning classifiers can be developed to objectively quantitate the pathological changes of villus blunting, intraepithelial lymphocytosis, and crypt hyperplasia in small intestine endoscopic biopsies. METHODS: A convolutional neural network (CNN) was trained and combined with a secondary algorithm to quantitate intraepithelial lymphocytes (IEL) with 5 classes on CD3 immunohistochemistry whole slide images (WSI) and used to correlate feature outputs with ground truth modified Marsh scores in a total of 116 small intestine biopsies. RESULTS: Across all samples, median %CD3 counts (positive cells/enterocytes) from villous epithelium (VE) increased with higher Marsh scores (Type 0%CD3 VE = 13.4; Type 1-3%CD3 VE = 41.9, p < 0.0001). Indicators of villus blunting and crypt hyperplasia were also observed (Type 0-2 villous epithelium/lamina propria area ratio = 0.81; Type 3a-3c villous epithelium/lamina propria area ratio = 0.29, p < 0.0001), and Type 0-1 crypt/villous epithelial area ratio = 0.59; Type 2-3 crypt/villous epithelial area ratio = 1.64, p < 0.0001). Using these individual features, a combined feature machine learning score (MLS) was created to evaluate a set of 28 matched pre- and post-intervention biopsies captured before and after dietary gluten restriction. The disposition of the continuous MLS paired biopsy result aligned with the Marsh score in 96.4% (27/28) of the cohort. CONCLUSIONS: Machine learning classifiers can be developed to objectively quantify histologic features and capture additional data not achievable with manual scoring. Such approaches should be further investigated to improve biopsy evaluation, especially for clinical trials.
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Doença Celíaca , Humanos , Doença Celíaca/diagnóstico , Doença Celíaca/patologia , Patologistas , Hiperplasia/patologia , Áreas Alagadas , Biópsia/métodos , Mucosa Intestinal/patologiaAssuntos
Linfoma de Célula do Manto/patologia , Adenina/análogos & derivados , Animais , Anticorpos Monoclonais Murinos/administração & dosagem , Anticorpos Monoclonais Murinos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ácidos Borônicos/administração & dosagem , Ácidos Borônicos/uso terapêutico , Bortezomib , Linhagem Celular Tumoral , Humanos , Linfoma de Célula do Manto/tratamento farmacológico , Linfoma de Célula do Manto/genética , Masculino , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Pessoa de Meia-Idade , Transplante de Neoplasias , Neoplasias Experimentais , Piperidinas , Pirazinas/administração & dosagem , Pirazinas/uso terapêutico , Pirazóis/administração & dosagem , Pirazóis/uso terapêutico , Pirimidinas/administração & dosagem , Pirimidinas/uso terapêutico , Rituximab , Células Tumorais CultivadasRESUMO
OBJECTIVES: Immunoglobulin M plasma cell myeloma (IgMPCM) is a rare entity that is difficult to distinguish from other IgM-related neoplasms. The study aims to characterize the clinicopathologic features of IgMPCM, including MYD88 L265P and CXCR4 mutations. METHODS: From our institutional archives, bone marrow biopsy specimens from January 1, 2008, to December 1, 2018, with monotypic plasma cells (PCs) expressing IgM that met current International Myeloma Working Group/World Health Organization criteria for PCM were included. Sanger sequencing was used to test for MYD88 L265P and WHIM-like CXCR4 mutations. RESULTS: Nine cases of IgMPCM were identified. Serum IgM paraproteins were detected in eight cases. CD138-positive PC burden averaged 41.9% (5%-80%). In four cases, PCs had lymphoplasmacytic morphology with cyclin D1 expression by immunohistochemistry. Three of four tested cases were positive for t(11;14) by fluorescence in situ hybridization, one with monosomy 13. The remaining case was positive for del13q14. All were negative for MYD88 L265P and WHIM-like CXCR4 mutations. Eight patients received immunochemotherapy, with four receiving autologous hematopoietic stem cell transplant. Median follow-up was 61 months (range, 11-120). All patients were alive except one. CONCLUSIONS: Distinguishing IgMPCM from other IgM-related disorders requires correlation with clinical, laboratory, and radiologic findings. Exclusion of MYD88 L265P and WHIM-like CXCR4 mutations may be useful to diagnose IgMPCM.