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ABSTRACT: Rearrangements that place the oncogenes MYC, BCL2, or BCL6 adjacent to superenhancers are common in mature B-cell lymphomas. Lymphomas with diffuse large B-cell lymphoma (DLBCL) or high-grade morphology with both MYC and BCL2 rearrangements are classified as high-grade B-cell lymphoma with MYC and BCL2 rearrangements ("double hit"; HGBCL-DH-BCL2) and are associated with aggressive disease and poor outcomes. Although it is established that MYC rearrangements involving immunoglobulin (IG) loci are associated with inferior outcomes relative to those involving other non-IG superenhancers, the frequency of and mechanisms driving IG vs non-IG MYC rearrangements have not been elucidated. Here, we used custom targeted capture and/or whole-genome sequencing to characterize oncogene rearrangements across 883 mature B-cell lymphomas including Burkitt lymphoma, follicular lymphoma, DLBCL, and HGBCL-DH-BCL2 tumors. We demonstrate that, although BCL2 rearrangement topology is consistent across entities, HGBCL-DH-BCL2 have distinct MYC rearrangement architecture relative to tumors with single MYC rearrangements or with both MYC and BCL6 rearrangements (HGBCL-DH-BCL6), including both a higher frequency of non-IG rearrangements and different architecture of MYC::IGH rearrangements. The distinct MYC rearrangement patterns in HGBCL-DH-BCL2 occur on the background of high levels of somatic hypermutation across MYC partner loci in HGBCL-DH-BCL2, creating more opportunity to form these rearrangements. Furthermore, because 1 IGH allele is already disrupted by the existing BCL2 rearrangement, the MYC rearrangement architecture in HGBCL-DH-BCL2 likely reflects selective pressure to preserve both BCL2 and B-cell receptor expression. These data provide new mechanistic explanations for the distinct patterns of MYC rearrangements observed across different lymphoma entities.
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Reordenamiento Génico , Proteínas Proto-Oncogénicas c-bcl-2 , Proteínas Proto-Oncogénicas c-myc , Humanos , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-myc/genética , Linfoma de Células B/genética , Linfoma de Células B/patología , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/patologíaRESUMEN
Silicon vacancy centers (SiVs) in diamond have emerged as a promising platform for quantum sciences due to their excellent photostability, minimal spectral diffusion, and substantial zero-phonon line emission. However, enhancing their slow nanosecond excited-state lifetime by coupling to optical cavities remains an outstanding challenge, as current demonstrations are limited to â¼10-fold. Here, we couple negatively charged SiVs to sub-diffraction-limited plasmonic cavities and achieve an instrument-limited ≤8 ps lifetime, corresponding to a 135-fold spontaneous emission rate enhancement and a 19-fold photoluminescence enhancement. Nanoparticles are printed on ultrathin diamond membranes on gold films which create arrays of plasmonic nanogap cavities with ultrasmall volumes. SiVs implanted at 5 and 10 nm depths are examined to elucidate surface effects on their lifetime and brightness. The interplay between cavity, implantation depth, and ultrathin diamond membranes provides insights into generating ultrafast, bright SiV emission for next-generation diamond devices.
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Activated B-cell-like diffuse large B-cell lymphoma (ABC-DLBCL) is an aggressive lymphoma characterized by constitutive NF-κB activation, but whether miR-17â¼92 contributes to this activation remains unclear. Herein, we sought to evaluate the role of miR-17â¼92 in the process of NF-κB activation in ABC-DLBCL. We found that the expression of miR-17â¼92 primary transcript was positively correlated with NF-κB activity, miR-17â¼92 activated the NF-κB signaling in ABC-DLBCL, and its over-expression promoted ABC-DLBCL cell growth, accelerated cell G1 to S phase transition and enhanced cell resistance to NF-κB inhibitor. Importantly, miR-17â¼92 promoted NF-κB activation through directly targeting multiple ubiquitin-editing regulators to lead to increase the K63-linked polyubiquitination and decrease the K48-linked polyubiquitination of RIP1 complex in ABC-DLBCL. We further found that miR-17â¼92 selectively activated IκB-α and NF-κB p65 but not NF-κB p52/p100, and high miR-17â¼92 expression was also associated with poorer outcome in ABC-DLBCL patients. Overall, our results showed that miR-17â¼92 selectively activated the canonical NF-κB signaling via targeting ubiquitin-editing regulators to lead to constitutively NF-κB activation and poorer outcome in ABC-DLBCL. These findings uncovered an innovative function of miR-17â¼92 and previously unappreciated regulatory mechanism of NF-κB activation in ABC-DLBCL. Targeting miR-17â¼92 may thus provide a novel bio-therapeutic strategy for ABC-DLBCL patients.
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Linfoma de Células B Grandes Difuso , MicroARNs , FN-kappa B , Ubiquitinación , Humanos , MicroARNs/genética , MicroARNs/metabolismo , FN-kappa B/metabolismo , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/metabolismo , Línea Celular Tumoral , Transducción de Señal , Masculino , Femenino , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética , Proteínas de Complejo Poro Nuclear/metabolismo , Proteínas de Complejo Poro Nuclear/genética , Regulación Neoplásica de la Expresión Génica , Persona de Mediana Edad , Proliferación Celular/genética , ARN Largo no CodificanteRESUMEN
Resonant enhancement of nonlinear photonic processes is critical for the scalability of applications such as long-distance entanglement generation. To implement nonlinear resonant enhancement, multiple resonator modes must be individually tuned onto a precise set of process wavelengths, which requires multiple linearly-independent tuning methods. Using coupled auxiliary resonators to indirectly tune modes in a multi-resonant nonlinear cavity is particularly attractive because it allows the extension of a single physical tuning mechanism, such as thermal tuning, to provide the required independent controls. Here we model and simulate the performance and tradeoffs of a coupled-resonator tuning scheme which uses auxiliary resonators to tune specific modes of a multi-resonant nonlinear process. Our analysis determines the tuning bandwidth for steady-state mode field intensity can significantly exceed the inter-cavity coupling rate g if the total quality factor of the auxiliary resonator is higher than the multi-mode main resonator. Consequently, over-coupling a nonlinear resonator mode to improve the maximum efficiency of a frequency conversion process will simultaneously expand the auxiliary resonator tuning bandwidth for that mode, indicating a natural compatibility with this tuning scheme. We apply the model to an existing small-diameter triply-resonant ring resonator design and find that a tuning bandwidth of 136â GHz ≈ 1.1 nm can be attained for a mode in the telecom band while limiting excess scattering losses to a quality factor of 106. Such range would span the distribution of inhomogeneously broadened quantum emitter ensembles as well as resonator fabrication variations, indicating the potential for the auxiliary resonators to enable not only low-loss telecom conversion but also the generation of indistinguishable photons in a quantum network.
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The current clinical management of Extranodal NK/T-cell lymphoma (ENKTL) primarily depends on conventional chemotherapy and radiotherapy, underscoring the need for innovative therapeutic strategies. This study explores the clinical significance and therapeutic implication of c-MYC (MYC) in ENKTL. Initially, we identified MYC protein overexpression in approximately 75% of cases within a large cohort of 111 patients. MYC overexpression was strongly correlated with lymphoma cell proliferation and poor clinical outcomes. Intriguingly, integrating MYC expression into the PINK-E prognostic model significantly enhanced its predictive power. Subsequently, we implemented MYC knockdown (KD) in NK malignancy cell lines with MYC overexpression, resulting in significant viability reduction. RNA-sequencing (RNA-seq) used to determine MYC function revealed a high overlap with canonical MYC-regulated genes and enrichment in metabolism and cell cycle regulation. Integrative analysis of the RNA-seq data upon MYC KD with gene expression profiles of primary ENKTL cases identified a subset of genes closely associated with MYC overexpression. Among these, CDK4 emerged as a potential therapeutic target, and its inhibition not only abrogated MYC function but also decreased MYC expression in NK malignancy cells. Furthermore, the clinical-grade CDK4/6 inhibitor palbociclib exhibited a potent anti-tumor effect in xenograft mouse models, especially when combined with gemcitabine. In summary, our study firmly establishes MYC as an oncogene with prognostic significance in ENKTL and highlights CDK4 inhibition as a promising therapeutic strategy for treating ENKTL with MYC overexpression.
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BACKGROUND: Multidrug resistance (MDR) limits successful cancer chemotherapy. P-glycoprotein (P-gp), BCRP and MRP1 are the key triggers of MDR. Unfortunately, no MDR modulator was approved by FDA to date. Here, we will investigate the effect of BI-2865, a pan-KRAS inhibitor, on reversing MDR induced by P-gp, BCRP and MRP1 in vitro and in vivo, and its reversal mechanisms will be explored. METHODS: The cytotoxicity of BI-2865 and its MDR removal effect in vitro were tested by MTT assays, and the corresponding reversal function in vivo was assessed through the P-gp mediated KBv200 xenografts in mice. BI-2865 induced alterations of drug discharge and reservation in cells were estimated by experiments of Flow cytometry with fluorescent doxorubicin, and the chemo-drug accumulation in xenografts' tumor were analyzed through LC-MS. Mechanisms of BI-2865 inhibiting P-gp substrate's efflux were analyzed through the vanadate-sensitive ATPase assay, [125I]-IAAP-photolabeling assay and computer molecular docking. The effects of BI-2865 on P-gp expression and KRAS-downstream signaling were detected via Western blotting, Flow cytometry and/or qRT-PCR. Subcellular localization of P-gp was visualized by Immunofluorescence. RESULTS: We found BI-2865 notably fortified response of P-gp-driven MDR cancer cells to the administration of chemo-drugs including paclitaxel, vincristine and doxorubicin, while such an effect was not observed in their parental sensitive cells and BCRP or MRP1-driven MDR cells. Importantly, the mice vivo combination study has verified that BI-2865 effectively improved the anti-tumor action of paclitaxel without toxic injury. In mechanism, BI-2865 prompted doxorubicin accumulating in carcinoma cells by directly blocking the efflux function of P-gp, which more specifically, was achieved by BI-2865 competitively binding to the drug-binding sites of P-gp. What's more, at the effective MDR reversal concentrations, BI-2865 neither varied the expression and location of P-gp nor reduced its downstream AKT or ERK1/2 signaling activity. CONCLUSIONS: This study uncovered a new application of BI-2865 as a MDR modulator, which might be used to effectively, safely and specifically improve chemotherapeutic efficacy in the clinical P-gp mediated MDR refractory cancers.
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Resistencia a Múltiples Medicamentos , Resistencia a Antineoplásicos , Humanos , Animales , Resistencia a Antineoplásicos/efectos de los fármacos , Resistencia a Múltiples Medicamentos/efectos de los fármacos , Ratones , Línea Celular Tumoral , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/antagonistas & inhibidores , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Ensayos Antitumor por Modelo de Xenoinjerto , Ratones Desnudos , Doxorrubicina/farmacología , Ratones Endogámicos BALB C , FemeninoRESUMEN
BACKGROUND: Neoadjuvant chemoradiotherapy (NCRT) followed by total mesorectal excision (TME) is the standard treatment for locally advanced rectal cancer (LARC). Mucinous adenocarcinoma (MAC) is a potential poor prognosis subgroup of rectal cancer. However, the predictive value of MAC in NCRT treatment of LARC is controversial. METHODS: A comprehensive literature search of PubMed, Embase, and the Cochrane Library was performed. All studies examining the effect of MAC on CRT response in LARC were included. Outcomes of MAC were compared with non-specific adenocarcinoma (AC) by using random-effects methods. Data were presented as odds ratios (ORs) with 95% confidence intervals (CIs). The main outcomes were the rates of pathological complete response (pCR), tumor and nodal down-staging, positive resection margin rate, local recurrence, and overall mortality. RESULTS: Fifteen studies containing comparative data on outcomes in a total of 9,238 patients receiving NCRT for LARC were eligible for inclusion. MAC had a reduced rate of pCR (OR, 0.38; 95% CI, 0.18-0.78) and tumor down-staging (OR, 0.31; 95% CI, 0.22-0.44) following NCRT compared with AC. MAC did not significantly affect nodal down-staging (OR, 0.42; 95% CI, 0.16-1.12) after NCRT. CONCLUSION: MAC of LARC was found to be a negative predictor of response to NCRT with lower rates of pCR and tumor down-staging for LARC. The nodal down-staging of MAC was relatively lower than that of AC, although the differences were not statistically significant.
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Adenocarcinoma Mucinoso , Terapia Neoadyuvante , Neoplasias del Recto , Neoplasias del Recto/terapia , Neoplasias del Recto/patología , Neoplasias del Recto/mortalidad , Humanos , Adenocarcinoma Mucinoso/terapia , Adenocarcinoma Mucinoso/patología , Adenocarcinoma Mucinoso/mortalidad , Estadificación de Neoplasias , Adenocarcinoma/terapia , Adenocarcinoma/patología , Adenocarcinoma/mortalidad , Recurrencia Local de Neoplasia , Pronóstico , Resultado del Tratamiento , Quimioradioterapia , Quimioradioterapia Adyuvante , Márgenes de EscisiónRESUMEN
Optically addressable solid-state defects are emerging as some of the most promising qubit platforms for quantum networks. Maximizing photon-defect interaction by nanophotonic cavity coupling is key to network efficiency. We demonstrate fabrication of gallium phosphide 1-D photonic crystal waveguide cavities on a silicon oxide carrier and subsequent integration with implanted silicon-vacancy (SiV) centers in diamond using a stamp-transfer technique. The stamping process avoids diamond etching and allows fine-tuning of the cavities prior to integration. After transfer to diamond, we measure cavity quality factors (Q) of up to 8900 and perform resonant excitation of single SiV centers coupled to these cavities. For a cavity with a Q of 4100, we observe a 3-fold lifetime reduction on-resonance, corresponding to a maximum potential cooperativity of C = 2. These results indicate promise for high photon-defect interaction in a platform which avoids fabrication of the quantum defect host crystal.
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BACKGROUND: There is limited knowledge about the impact of painful temporomandibular disorders (TMDs) and pain characteristics on jaw functional limitation and oral health-related quality of life (OHRQoL) in TMD patients. OBJECTIVES: The influence of painful TMDs and pain characteristics on jaw functional limitation and OHRQoL was investigated. Inter-relationships between limitation in jaw function and various OHRQoL domains, along with facial pain attributes predicting impaired jaw function and diminished OHRQoL were also examined. METHODS: TMD patients were recruited from a university-based hospital. A comprehensive questionnaire comprising demographic variables, the DC/TMD Symptom Questionnaire, Graded Chronic Pain Scale, Jaw Functional Limitation Scale-8 (JFLS-8) and Oral Health Impact Profile-TMD (OHIP-TMD) was administered. Participants underwent a protocolized physical examination, and TMD diagnoses were determined utilising the DC/TMD algorithms. Participants were subsequently stratified into intra-articular/pain-related/combined TMD groups, as well as no TMD pain, acute/chronic pain and low/high-intensity pain groups. Data were assessed using non-parametric and hierarchical linear regression analyses (α = .05). RESULTS: The final sample consisted of 280 participants (mean age 31.2 (SD 11.8) years; 79.3% women). Significant differences in pain characteristics, JFLS-8, and global OHIP scores were observed across the various TMD subtypes, pain chronicity and pain intensity categories. Pain intensity and pain-related interference exhibited moderate correlations with JFLS-8 and global OHIP scores (rs = 0.53-0.60). Moderate associations were also noted between JFLS-8 and global OHIP, as well as most OHIP domains (rs = 0.42-0.64). Both jaw functional limitation and OHRQoL were predicted by sex, pain intensity and pain-related interference. CONCLUSIONS: Sex, pain intensity and pain-related interference are key determinants for both impaired jaw function and diminished OHRQoL, with pain-related interference exerting a more pronounced effect.
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Dolor Facial , Salud Bucal , Dimensión del Dolor , Calidad de Vida , Trastornos de la Articulación Temporomandibular , Humanos , Femenino , Masculino , Trastornos de la Articulación Temporomandibular/fisiopatología , Trastornos de la Articulación Temporomandibular/psicología , Trastornos de la Articulación Temporomandibular/complicaciones , Dolor Facial/fisiopatología , Dolor Facial/psicología , Adulto , Encuestas y Cuestionarios , Persona de Mediana Edad , Dolor Crónico/fisiopatología , Dolor Crónico/psicología , Adulto JovenRESUMEN
During choriogenesis in insects, chorion (eggshell) is formed by surrounding follicular epithelial cells in ovarioles. However, the regulatory endocrine factor(s) activating choriogenesis and the effect of chemical components on eggshell deserve further exploration. In two representative coleopterans, a coccinellid Henosepilachna vigintioctopunctata and a chrysomelid Leptinotarsa decemlineata, genes encoding the 20-hydroxyecdysone (20E) receptor heterodimer, ecdysone receptor (EcR) and ultraspiracle (USP), and two chitin biosynthesis enzymes UDP-N-acetylglucosamine pyrophosphorylase (UAP) and chitin synthase (ChS1), were highly expressed in ovaries of the young females. RNA interference (RNAi)-aided knockdown of either HvEcR or Hvusp in H. vigintioctopunctata inhibited oviposition, suppressed the expression of HvChS1, and lessened the positive signal of Calcofluor staining on the chorions, which suggests the reduction of a chitin-like substance (CLS) deposited on eggshells. Similarly, RNAi of LdEcR or Ldusp in L. decemlineata constrained oviposition, decreased the expression of LdUAP1 and LdChS1, and reduced CLS contents in the resultant ovaries. Knockdown of LdUAP1 or LdChS1 caused similar defective phenotypes, i.e., reduced oviposition and CLS contents in the L. decemlineata ovaries. These results, for the first time, indicate that 20E signaling activates choriogenesis in two coleopteran species. Moreover, our findings suggest the deposition of a CLS on the chorions.
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Escarabajos , Ecdisona , Interferencia de ARN , Receptores de Esteroides , Transducción de Señal , Animales , Escarabajos/metabolismo , Escarabajos/genética , Femenino , Ecdisona/metabolismo , Proteínas de Insectos/metabolismo , Proteínas de Insectos/genética , Oviposición/efectos de los fármacos , Cáscara de Huevo/metabolismo , Ovario/metabolismoRESUMEN
Aqueous Zn-ion batteries are an attractive electrochemical energy storage solution for their budget and safe properties. However, dendrites and uncontrolled side reactions in anodes detract the cycle life and energy density of the batteries. Grain boundaries in metals are generally considered as the source of the above problems but we present a diverse result. This study introduces an ultra-high proportion of grain boundaries on zinc electrodes through femtosecond laser bombardment to enhance stability of zinc metal/electrolyte interface. The ultra-high proportion of grain boundaries promotes the homogenization of zinc growth potential, to achieve uniform nucleation and growth, thereby suppressing dendrite formation. Additionally, the abundant active sites mitigate the side reactions during the electrochemical process. Consequently, the 15â µm Fs-Zn||MnO2 pouch cell achieves an energy density of 249.4â Wh kg-1 and operates for over 60 cycles at a depth-of-discharge of 23 %. The recognition of the favorable influence exerted by UP-GBs paves a new way for other metal batteries.
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OX40 enhances the T-cell activation via costimulatory signaling. However, its molecular characteristics and value in predicting response to immunochemotherapy in DLBCL remain largely unexplored. Here, we performed an integrative analysis of sequencing and multiplex immunofluorescence staining, and discovered abnormally higher expression of OX40 in DLBCL patients. Elevated OX40 could activate T cells leading to a higher immune score for tumor immune microenvironment (TiME). OX40 upregulation simultaneously happened with immune-related genes including PD-1, CTLA4 and TIGIT et,al. Patients with high OX40 expression exhibited a lower Ann Arbor stage and IPI score and more easily achieved a complete response/partial response. The analysis of infiltrated T-cell subset revealed that patients with a greater number of CD4+/OX40+ or CD8+/OX40+ T cells had a longer OS. Our findings indicated that OX40 shapes an inflamed tumor immune microenvironment and predicts response to immunochemotherapy, providing insights for the application of OX40 agonist in DLBCL patients.
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Linfoma de Células B Grandes Difuso , Humanos , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/genética , Linfocitos T CD8-positivos , Subgrupos de Linfocitos T/patología , Transducción de Señal , Microambiente Tumoral , PronósticoRESUMEN
PURPOSE: Triple-negative breast cancer (TNBC) represents the worst prognostic subtype of breast cancer and lacks targeted therapeutic drugs. Signal transducer and activator of transcription 3 (STAT3) is overexpressed and constitutively activated in TNBCs and associated with poor patient outcomes. However, no agents targeting STAT3 have been successfully developed and marketed. Selective Estrogen Receptor Modulators (SERMs) have been reported as potential inhibitors of the IL-6/STAT3 signaling pathway. Naphthalene compounds have good pharmacological activity and significant anti-cancer activity. In this study, we synthesized a new series of naphthalene derivatives with the general structure of SERM and evaluated their effects on TNBC and STAT3 signals. METHODS: A new series of compounds based on the scaffold of SERMs and an amino group were designed and screened based on the structure-activity relationship by MTT assay. The binding activity of SMY002 to STAT3 was predicted and validated by docking and SPR. The STAT3 signaling target and anti-cancer effects of SMY002 were evaluated with three TNBC cell lines and the mice transplanted tumor model. RESULTS: Among the compounds, SMY002 displayed the most potent activity, which could directly interact with STAT3 SH2-domain, and strongly inhibit the phosphorylation, dimerization, nuclear distribution, transcriptional activity, and target genes expression of STAT3. Furthermore, SMY002 markedly suppressed migration, invasion, survival, growth, and metastasis of TNBC cells in vitro and in vivo via down-regulating the expression of Cyclin D1 and MMP9. CONCLUSIONS: SMY002 can significantly inhibit the growth and metastasis of TNBC cells by targeting the STAT3 signal.
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Neoplasias de la Mama Triple Negativas , Humanos , Animales , Ratones , Neoplasias de la Mama Triple Negativas/patología , Factor de Transcripción STAT3/metabolismo , Moduladores Selectivos de los Receptores de Estrógeno/farmacología , Transducción de Señal , Proliferación Celular , Naftalenos/farmacología , Naftalenos/uso terapéutico , Línea Celular TumoralRESUMEN
We demonstrate quasi-phase matched, triply-resonant sum frequency conversion in 10.6-µm-diameter integrated gallium phosphide ring resonators. A small-signal, waveguide-to-waveguide power conversion efficiency of 8 ± 1.1%/mW; is measured for conversion from telecom (1536 nm) and near infrared (1117 nm) to visible (647 nm) wavelengths with an absolute power conversion efficiency of 6.3 ± 0.6%; measured at saturation pump power. For the complementary difference frequency generation process, a single photon conversion efficiency of 7.2%/mW from visible to telecom is projected for resonators with optimized coupling. Efficient conversion from visible to telecom will facilitate long-distance transmission of spin-entangled photons from solid-state emitters such as the diamond NV center, allowing long-distance entanglement for quantum networks.
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Patients with synchronous malignancies can be problematic to diagnose and manage because workup and therapeutic targeting for each individual malignancy must be coordinated carefully. This report presents a patient with concurrent chronic myeloid leukemia (CML) and chronic lymphocytic leukemia (CLL) managed with concomitant venetoclax and imatinib. Because imatinib is a moderate cytochrome P450 3A4 inhibitor, close monitoring is required when using with a substrate of 3A4 such as venetoclax. Although the target dose of venetoclax is 400 mg, it was capped at 100 mg due to the interaction. Despite the interaction and possible enhancement of toxicities, the patient has tolerated therapy well, and both diseases have responded to this novel approach. In addition, because aberrant BCL-2 activity has been implicated in CML, the use of venetoclax may contribute to success in the management of this patient's CML. This case report represents the safe concomitant use of venetoclax and imatinib in a patient with synchronous CML and CLL.
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Antineoplásicos , Leucemia Linfocítica Crónica de Células B , Leucemia Mielógena Crónica BCR-ABL Positiva , Humanos , Mesilato de Imatinib/uso terapéutico , Leucemia Linfocítica Crónica de Células B/diagnóstico , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Leucemia Linfocítica Crónica de Células B/patología , Antineoplásicos/uso terapéutico , Leucemia Mielógena Crónica BCR-ABL Positiva/diagnóstico , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológicoRESUMEN
Eleven densely functionalized new dihydro-ß-agarofuran sesquiterpenoid derivatives, named maytenoids A-K (1-11), as well as one known analog, were isolated and characterized from Maytenus austroyunnanensis. Their structures were assigned based on analysis of spectroscopic data and X-ray crystallography. Compounds 1-9 are macrocyclic sesquiterpene pyridine alkaloids generated by the respective acylation of the hydroxy groups at C-3 and C-13 of dihydro-ß-agarofuran sesquiterpenoids via diverse pyridine dicarboxylic acids. Compounds 1, 2, 5-10, and 12 exhibited significant inhibitory effects on NO production at 10 µM in lipopolysaccharide (LPS)-stimulated BV2 cells.
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Alcaloides , Maytenus , Sesquiterpenos , Maytenus/química , Estructura Molecular , Alcaloides/farmacología , Alcaloides/química , Sesquiterpenos/farmacología , Sesquiterpenos/química , Piridinas/químicaRESUMEN
It is of great significance to develop the effective technique to treat phenol-containing wastewater. Herein, Fe-based prussian blue analogues-derived zero valent iron (ZVI) was successfully synthesized by one-step calcination method. Owing to high specific surface area and rich active sites, ZVI-2 possessed excellent performance in charge transfer. Notably, in comparison with conventional ZVI and Fe2+, ZVI-2 can effectively activate peroxymonosulfate (PMS) for achieving rapid degradation of phenol, and the highest removal efficiency of phenol reached 94.9% within 24 min. More importantly, developed ZVI-2/PMS oxidation system with good stability displayed strong anti-interference capability. Interestingly, Fe0 loaded on the surface of ZVI-2 can efficiently break the O-O bond of PMS to generate reactive oxygen species (i.e., SO4â¢-, OHâ¢, O2â¢- and 1O2). As main adsorption sites of PMS, the existence of oxygen vacancy promote the formation of high-valent transition metal complexes (namely ZVI-2≡Fe4+=O). Under the combined action of reactive oxygen species and ZVI-2≡Fe4+=O, phenol can be eventually degraded into CO2 and H2O. The possible degradation pathways of phenol were also investigated. Furthermore, proposed ZVI-2/PMS oxidation system displayed great potential for application in the field of wastewater treatment. All in all, current work provided a valuable reference for design and application of Fe-based catalysts in PS-AOPs.
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BACKGROUND: We aimed to explore the roles of T helper 17 (Th17) cells and cytokines interleukin 17 (IL-17), IL-6, IL-4, transforming growth factor ß (TGF-ß) and γ-interferon (IFN-γ) in the peripheral blood of patients with non-small cell lung cancer (NSCLC) of different clinical stages, pathological types, and differentiation degrees. METHODS: A total of 120 NSCLC patients admitted and 80 healthy people receiving physical examinations from June 2019 to October 2021 were enrolled as the case group (TNM stage: I, II, III and IV; pathological type: adenocarcinoma and squamous cell carcinoma; differentiation degree: low and moderate-high) and the control group, respectively. The serum levels of IL-17, IL-6, IL-4, TGF-ß and IFN-γ were measured using an enzyme-linked immunosorbent assay. Th17 cells were counted by flow cytometry. RESULTS: The case group had higher levels of Th17 cells, IL-17, IL-6, IL-4, and TGF-ß and lower IFN-γ level in the peripheral blood than those of the control group (p < 0.05). NSCLC patients with different TNM stages had significantly different levels of Th17 cell, IL-17, IL-6, TGF-ß, and IFN-γ (p < 0.05). The expression levels of Th17 and IL-6 in patients with lowly differentiated NSCLC were lower than those of patients with moderately and highly differentiated NSCLC, while the IFN-γ expression level followed an opposite trend (p < 0.05). The count of Th17 cells in the peripheral blood of NSCLC patients had significantly positive correlations with IL-17, IL-6, IL-4, and TGF-ß levels, but negative correlation with IFN-γ level (p < 0.05). CONCLUSIONS: The count of Th17 cells increases significantly in NSCLC patients and has correlations with TNM stage and differentiation degree.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Células Th17/metabolismo , Interleucina-17/metabolismo , Interleucina-6 , Interleucina-4/metabolismo , Neoplasias Pulmonares/patología , Factor de Crecimiento Transformador beta/metabolismo , Interferón gamma , Diferenciación CelularRESUMEN
OBJECTIVES: This study examined the metric properties of the Oral Health Impact Profile for Temporomandibular Disorders (OHIP-TMD) using Factor/Rasch analyses and created a short-form version of the measure. SUBJECTS AND METHODS: Aggregated OHIP-TMD data were obtained from a cross-sectional study involving 844 TMD patients with diagnostic criteria for TMDs defined conditions. The dimensionality of the OHIP-TMD was first evaluated with exploratory factor analysis. An eigenvalue >1.0 and oblique oblimin rotation were applied for extracting the factors. Rasch analysis was subsequently performed on the primary dimension using the ConQuest software. RESULTS: Multi-dimensionality of the OHIP-TMD was observed with the primary dimension comprising ten items. Adequate fit to the Rasch model was noted after deleting item 8 with infit/outfit mean-square values ranging from 0.75 to 1.40 logits. Item difficulty ranged from -0.75 to 1.05 logits, while participants' ability to respond varied from -4.55 to 5.19 logits. The respondent spread was slightly skewed and satisfactory item-response targeting was present. CONCLUSIONS: The 22-item OHIP-TMD demonstrated multi-dimensionality with the primary dimension consisting of nine reliable items with adequate fit to the Rasch model. The 9-item short-form version of the OHIP-TMD (SOHIP-TMD) is a promising tool for evaluating OHRQoL.
Asunto(s)
Calidad de Vida , Trastornos de la Articulación Temporomandibular , Humanos , Salud Bucal , Estudios Transversales , Trastornos de la Articulación Temporomandibular/diagnóstico , Encuestas y CuestionariosRESUMEN
BACKGROUND: There is no consensus regarding the superiority of volatile or total intravenous anesthesia (TIVA) in reducing the incidence of postoperative pulmonary complications (PPCs) after lung resection surgery (LRS). Thus, the aim of this study was to investigate the different anesthetic regimens and the incidence of PPCs in patients who underwent LRS. We hypothesized that TIVA is associated with a lower incidence of PPCs than volatile anesthesia. METHODS: This was a retrospective cohort study of patients who underwent LRS at Taipei Veterans General Hospital between January 2016 and December 2020. The patients' charts were reviewed and data on patient characteristics, perioperative features, and postoperative outcomes were extracted and analyzed. The patients were categorized into TIVA or volatile anesthesia groups and their clinical data were compared. Propensity score matching was performed to reduce potential selection bias. The primary outcome was the incidence of PPCs, whereas the secondary outcomes were the incidences of other postoperative events, such as length of hospital stay (LOS) and postoperative nausea and vomiting (PONV). RESULTS: A total of 392 patients each were included in the TIVA and volatile anesthesia groups. There was no statistically significant difference in the incidence of PPCs between the volatile anesthesia and TIVA groups. The TIVA group had a shorter LOS (p < 0.001) and a lower incidence of PONV than the volatile anesthesia group (4.6% in the TIVA group vs. 8.2% in the volatile anesthesia group; p = 0.041). However, there were no significant differences in reintubation, 30-day readmission, and re-operation rates between the two groups. CONCLUSIONS: There was no significant difference between the incidence of PPCs in patients who underwent LRS under TIVA and that in patients who underwent LRS under volatile anesthesia. However, TIVA had shorter LOS and lower incidence of PONV which may be a better choice for maintenance of anesthesia in patients undergoing LRS.