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Glucuronidation, a crucial process in phase II metabolism, plays a vital role in the detoxification and elimination of endogenous substances and xenobiotics. A comprehensive and confident profiling of glucuronate-conjugated metabolites is imperative to understanding their roles in physiological and pathological processes. In this study, a chemical isotope labeling and dual-filtering strategy was developed for global profiling of glucuronide metabolites in biological samples. N,N-Dimethyl ethylenediamine (DMED-d0) and its deuterated counterpart DMED-d6 were used to label carboxylic acids through an amidation reaction. First, carboxyl-containing compounds were extracted based on a characteristic mass difference (Δm/z, 6.037 Da) observed in MS between light- and heavy-labeled metabolites (filter I). Subsequently, within the pool of carboxyl-containing compounds, glucuronides were identified using two pairs of diagnostic ions (m/z 247.1294/253.1665 and 229.1188/235.1559 for DMED-d0/DMED-d6-labeled glucuronides) originating from the fragmentation of the derivatized glucuronic acid group in MS/MS (filter II). Compared with non-derivatization, DEMD labeling significantly enhanced the detection sensitivity of glucuronides, as evidenced by a 3- to 55-fold decrease in limits of detection for representative standards. The strategy was applied to profiling glucuronide metabolites in urine samples from colorectal cancer (CRC) patients. A total of 685 features were screened as potential glucuronides, among which 181 were annotated, mainly including glucuronides derived from lipids, organic oxygen, and phenylpropanoids. Enzymatic biosynthesis was employed to accurately identify unknown glucuronides without standards, demonstrating the reliability of the dual-filtering strategy. Our strategy exhibits great potential for profiling the glucuronide metabolome with high coverage and confidence to reveal changes in CRC and other diseases.
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The chromogenic reaction between 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate) (ABTS) and ferrate [Fe(VI)] has long been utilized for Fe(VI) content measurement. However, the presence of electron-rich organic compounds has been found to significantly impact Fe(VI) detection using the ABTS method, leading to relative errors ranging from â¼88 to 100%. Reducing substances consumed ABTSâ¢+ and resulted in underestimated Fe(VI) levels. Moreover, the oxidation of electron-rich organics containing hydroxyl groups by Fe(VI) could generate a phenoxyl radical (Phâ¢), promoting the transformation of Fe(VI) â Fe(V) â Fe(IV). The in situ formation of Fe(IV) can then contribute to ABTS oxidation, altering the ABTSâ¢+:Fe(VI) stoichiometry from 1:1 to 2:1. To overcome these challenges, we introduced Mn(II) as an activator and 3,3',5,5'-tetramethylbenzidine (TMB) as a chromogenic agent for Fe(VI) detection. This Mn(II)/TMB method enables rapid completion of the chromogenic reaction within 2 s, with a low detection limit of approximately 4 nM and a wide detection range (0.01-10 µM). Importantly, the Mn(II)/TMB method exhibits superior resistance to reductive interference and effectively eliminates the impact of phenoxyl-radical-mediated intermediate valence iron transfer processes associated with electron-rich organic compounds. Furthermore, this method is resilient to particle interference and demonstrates practical applicability in authentic waters.
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Electrones , Oxidación-Reducción , Hierro/química , Compuestos Orgánicos/química , Benzotiazoles/química , Ácidos SulfónicosRESUMEN
OBJECTIVE: Multi-energy CT conducted by photon-counting detector has a wide range of applications, especially in multiple contrast agents imaging. However, static multi-energy (SME) CT imaging suffers from higher statistical noise because of increased energy bins with static energy thresholds. Our team has proposed a dynamic dual-energy (DDE) CT detector model and the corresponding iterative reconstruction algorithm to solve this problem. However, rigorous and detailed analysis of the statistical noise characterization in this DDE CT was lacked. APPROACH: Starting from the properties of the Poisson random variable, this paper analyzes the noise characterization of the DDE CT and compares it with the SME CT. It is proved that the multi-energy CT projections and reconstruction images calculated from the proposed DDE CT algorithm have less statistical noise than that of the SME CT. MAIN RESULTS: Simulations and experiments verify that the expectations of the multi-energy CT projections calculated from DDE CT are the same as those of the SME projections. Still, the variance of the former is smaller. We further analyze the convergence of the iterative DDE CT algorithm through simulations and prove that the derived noise characterization can be realized under different CT imaging configurations. SIGNIFICANCE: The low statistical noise characteristics demonstrate the value of DDE CT imaging technology.
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PURPOSE: PSMA/PET has been increasingly used to detect PCa, and PSMA/PET-guided biopsy has shown promising results. However, it cannot be confirmed immediately whether the tissues are the targeted area. In this study, we aimed to develop a novel probe, [123I]I-PSMA-7. First, we hope that [123I]I-PSMA-7 can provide instant confirmation for prostate biopsy. Second, we hope it will help detect PCa. METHODS: We synthesized a high-affinity probe, [123I]I-PSMA-7, and evaluated its properties. We included ten patients with suspected PCa and divided them into two groups. The injection and biopsy were approximately 24 h apart. The activity in biopsy lesions was measured as the cpm by a γ-counter. Moreover, we enrolled 3 patients to evaluate the potential of [123I]I-PSMA-7 for detecting PCa. RESULTS: Animal experiments verified the safety, targeting and effectiveness of [123I]I-PSMA-7, and the tumor-to-muscle ratio was greatest at 24 h, which confirmed the results of this study in humans. After injection of 185MBq [123I]I-PSMA-7, 18/55 cores were positive, and the cpm was significantly greater (4345 ± 3547 vs. 714 ± 547, P < 0.001), with an AUC of 0.97 and a cutoff of 1312 (sens/spec of 94.40%/91.90%). At a lower dose, 10/55 biopsy cores were cancerous, and the cpm was 2446 ± 1622 vs. 153 ± 112 (P < 0.001). The AUC was 1, with a cutoff value of 490 (sens/spec of 100%). When the radiopharmaceuticals were added to 370 MBq, we achieved better SPECT/CT imaging. CONCLUSION: With the aid of [123I]I-PSMA-7 and via cpm-based biopsy, we can reduce the number of biopsies to a minimum operation. [123I]I-PSMA-7 PSMA SPECT/CT can also provide good imaging results. TRIAL REGISTRATION: Chinese Clinical trial registry ChiCTR2300069745, Registered 24 March 2023.
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The manufacturability assessment and optimization of bispecific antibodies (bsAbs) during the discovery stage are crucial for the success of the drug development process, impacting the speed and cost of advancing such therapeutics to the Investigational New Drug (IND) stage and ultimately to the market. The complexity of bsAbs creates challenges in employing effective evaluation methods to detect developability risks in early discovery stage, and poses difficulties in identifying the root causes and implementing subsequent engineering solutions. This study presents a case of engineering a bsAb that displayed a normal solution appearance during the discovery phase but underwent significant precipitation when subjected to agitation stress during 15 L Chemistry, Manufacturing, and Control (CMC) production Leveraging analytical tools, structural analysis, in silico prediction, and wet-lab validations, the key molecular origins responsible for the observed precipitation were identified and addressed. Sequence engineering to reduce protein surface hydrophobicity and enhance conformational stability proved effective in resolving agitation-induced aggregation. The refined bsAb sequences enabled successful mass production in CMC department. The findings of this case study contribute to the understanding of the fundamental mechanism of agitation-induced aggregation and offer a potential protein engineering procedure for addressing similar issues in bsAb. Furthermore, this case study emphasizes the significance of a close partnership between Discovery and CMC teams. Integrating CMC's rigorous evaluation methods with Discovery's engineering capability can facilitate a streamlined development process for bsAb molecules.
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Although small pore Cu-SSZ-13 catalysts have been successful as commercial catalysts for controlling NOx emissions from mobile sources, the challenges of high light-off temperature, SO2 tolerance and hydrothermal stability still need to be addressed. Here, we synthesized a multifunctional core-shell catalyst with Cu-SSZ-13 as the core phase and Ce-MnOx supported Mesoporous-silica (Meso-SiO2) as the shell phase via self-assembly and impregnation. The core-shell catalyst exhibited excellent low-temperature activity, SO2 tolerance and hydrothermal stability compared to the Cu-SSZ-13. The Ce-MnOx species dispersed in the shell are found to enhance both the acidic and oxidative properties of the core-shell catalyst. More critically, these species can rapidly activate NO and oxidize it to NO2, which allows the NH3-SCR reaction on the core-shell catalyst to be initiated in the shell phase. Meanwhile, Ce-MnOx species can react preferentially with SO2 as sacrifice components, effectively avoiding the sulfur inactivation of the copper active sites. Furthermore, the hydrophobic Meso-SiO2 shell provides an important barrier for the core phase, which reduces the loss of active species, acid sites and framework Al of the aged core-shell catalyst and mitigates the collapse of the zeolite framework. This work provides a new strategy for the design of novel and efficient NH3-SCR catalysts.
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MYC2 is a class of bHLH family transcription factors and a major regulatory factor in the JA signaling pathway, and its molecular function in tobacco has not been reported. In this study, CRISPR/Cas9-mediated MYC2 gene NtMYC2a knockout mutants at tobacco was obtained and its agronomic traits, disease resistance, and chemical composition were identified. Comparing with the WT, the leaf width of the KO-NtMYC2a was narrowed, the nornicotine content and mecamylamine content increased significantly and the resistance to Ralstonia solanacearum significantly decreased. The transcriptome sequencing results showed that DEGs related to immunity, signal transduction and growth and development were enriched between KO-NtMYC2a and WT. NtJAR1 and NtCOI1 in KO-NtMYC2a were down-regulated to regulating the JA signaling pathway, result in a significant decrease in tobacco's resistance to R. solanacearum. Our research provides theoretical support for the functional research of MYC2 and the study of the mechanism of tobacco bacterial wilt resistance.
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Sistemas CRISPR-Cas , Resistencia a la Enfermedad , Regulación de la Expresión Génica de las Plantas , Nicotiana , Enfermedades de las Plantas , Proteínas de Plantas , Ralstonia solanacearum , Nicotiana/genética , Nicotiana/microbiología , Resistencia a la Enfermedad/genética , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/genética , Ralstonia solanacearum/patogenicidad , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Técnicas de Inactivación de Genes , Ciclopentanos/metabolismo , Transducción de Señal , Oxilipinas/metabolismo , Plantas Modificadas Genéticamente/genéticaRESUMEN
OBJECTIVE: To examine the effectiveness of Chinese medicine (CM) Lianhua Qingwen Granule (LHQW) and Jingyin Gubiao Prescription (JYGB) in asymptomatic or mild patients with Omicron infection in the shelter hospital. METHODS: This single-center retrospective cohort study was conducted in the largest shelter hospital in Shanghai, China, from April 10, 2022 to May 30, 2022. A total of 56,244 asymptomatic and mild Omicron cases were included and divided into 4 groups, i.e., non-administration group (23,702 cases), LHQW group (11,576 cases), JYGB group (12,112 cases), and dual combination of LHQW and JYGB group (8,854 cases). The length of stay (LOS) in the hospital was used to assess the effectiveness of LHQW and JYGB treatment on Omicron infection. RESULTS: Patients aged 41-60 years, with nadir threshold cycle (CT) value of N gene <25, or those fully vaccinated preferred to receive CM therapy. Before or after propensity score matching (PSM), the multiple linear regression showed that LHQW and JYGB treatment were independent influence factors of LOS (both P<0.001). After PSM, there were significant differences in LOS between the LHQW/JYGB combination and the other groups (P<0.01). The results of factorial design ANOVA proved that the LHQW/JYGB combination therapy synergistically shortened LOS (P=0.032). CONCLUSIONS: Patients with a nadir CT value <25 were more likely to accept CM. The LHQW/JYGB combination therapy could shorten the LOS of Omicron-infected individuals in an isolated environment.
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BACKGROUND: Forest geneticists typically use provenances to account for population differences in their improvement schemes; however, the historical records of the imported materials might not be very precise or well-aligned with the genetic clusters derived from advanced molecular techniques. The main objective of this study was to assess the impact of marker-based population structure on genetic parameter estimates related to growth and wood properties and their trade-offs in Norway spruce, by either incorporating it as a fixed effect (model-A) or excluding it entirely from the analysis (model-B). RESULTS: Our results indicate that models incorporating population structure significantly reduce estimates of additive genetic variance, resulting in substantial reduction of narrow-sense heritability. However, these models considerably improve prediction accuracies. This was particularly significant for growth and solid-wood properties, which showed to have the highest population genetic differentiation (QST) among the studied traits. Additionally, although the pattern of correlations remained similar across the models, their magnitude was slightly lower for models that included population structure as a fixed effect. This suggests that selection, consistently performed within populations, might be less affected by unfavourable genetic correlations compared to mass selection conducted without pedigree restrictions. CONCLUSION: We conclude that the results of models properly accounting for population structure are more accurate and less biased compared to those neglecting this effect. This might have practical implications for breeders and forest managers where, decisions based on imprecise selections can pose a high risk to economic efficiency.
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Picea , Madera , Picea/genética , Picea/crecimiento & desarrollo , Madera/genética , Marcadores Genéticos/genética , Modelos Genéticos , Genética de Población/métodos , Variación Genética/genéticaRESUMEN
To investigate the feasibility of conventional (basketing + dusting) and Moses (pop-dusting) holmium lasers during flexible ureteroscopy (FURS) in the treatment of 2-3 cm renal calculi and to compare the efficiency and safety of the two methods, a total of 230 patients with 2-3 cm kidney stones who underwent FURS were randomly divided into the conventional group and the Moses group. The mode of lithotripsy in the conventional group was fragmentation and dusting. The mode of lithotripsy in the Moses group was dusting and pop-dusting. Clinical and perioperative variables and complications were compared between the two cohorts. Multivariate analyses of factors contributing to the stone-free rate (SFR) and operation time were performed. No statistically significant differences were found in the demographics, renal stone-related data, SFR, or complications between the cohorts. The laser energy was higher in the Moses cohort than in the conventional cohort (119.3 ± 15.2 vs. 92.8 ± 15.1 kJ; P < 0.001), and the operation time was shorter in the Moses cohort than in the conventional cohort (99.5 ± 18.9 vs. 105.3 ± 13.7 min; P = 0.009). When there was isolated stone, the operation time was shorter in the Moses cohort than in the conventional cohort (99.6 ± 17.5 vs. 111.4 ± 10.7 min; P < 0.001), while there was no significant difference between the two cohorts when there were multiple stones (99.5 ± 20 vs. 101.2 ± 14 min; P = 0.415). Multivariate analyses found that an increase in stone volume can decrease the SFR and prolong the operation time, and use of a Moses laser can shorten the operation time. Both holmium laser modes during FURS can effectively treat 2-3 cm renal calculi. The Moses mode is recommended as the first choice for the treatment of isolated 2-3 cm renal stones. When treating multiple stones, the efficiency of these two laser modalities is the same. TRIAL REGISTRATION: ChiCTR2200056091.
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Cálculos Renales , Láseres de Estado Sólido , Litotripsia por Láser , Tempo Operativo , Ureteroscopía , Humanos , Ureteroscopía/métodos , Ureteroscopía/efectos adversos , Ureteroscopía/instrumentación , Cálculos Renales/cirugía , Láseres de Estado Sólido/uso terapéutico , Femenino , Masculino , Persona de Mediana Edad , Litotripsia por Láser/métodos , Litotripsia por Láser/instrumentación , Litotripsia por Láser/efectos adversos , Adulto , Resultado del Tratamiento , Estudios de Factibilidad , AncianoRESUMEN
The utilization of biodegradable mulch films (bio-MFs) is essential for agricultural safety. This study explored the effects of no MF (CK), aging bio-MF (BM), non-aging bio-MF (NBM), and aging polyethylene (PE)-MF (PEM) on swine manure composting. The results demonstrated that outdoor aging (45 days) accelerated the macroscopic degradation of bio-MF in the BM. A reduction in NH4+-N and NH3 emissions in the initial composting was observed owing to an increase in the carbon source or the bulking effect provided by the MFs. N2O emissions from days 9 to 21 were higher in the PEM than other treatments because of the formation of anaerobic zone in the MF-based aggregates. An obvious increase of amoA in PEM indicated a promoted nitrification during the maturation phase, meanwhile the increase of NO2--N and aggregate promoted denitrification. Altogether, MF influenced composting through the synergistic effects of increasing the carbon source, bulking effect, and aggregates.
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Compostaje , Estiércol , Nitrógeno , Animales , Compostaje/métodos , Porcinos , Biodegradación Ambiental , Agricultura/métodos , Sus scrofa , Polietileno/químicaRESUMEN
A frozen-temperature (below -28 °C) laser tuning way is developed to optimize metal halide perovskite (MHP)'s stability and opto-electronic properties, for emitter, photovoltaic and detector applications. Here freezing can adjust the competitive laser irradiation effects between damaging and annealing/repairing. And the ligand shells on MHP surface, which are widely present for many MHP materials, can be frozen and act as transparent solid templates for MHP's re-crystallization/re-growth during the laser tuning. With model samples of different types of CsPbBr3 nanocube arrays,an attempt is made to turn the dominant exposure facet from low-energy [100] facet to high-energy [111], [-211], [113] and [210] ones respectively; selectively removing the surface impurities and defects of CsPbBr3 nanocubes to enhance the irradiation durability by 101 times; and quickly (tens of seconds) modifying a Ruddlesden-Popper (RP) boundary into another type of boundary like twinning, and so on. The laser tuning mechanism is revealed by an innovative in situ cryo-transmission electron microscope (cryo-TEM) exploration at atomic resolution.
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To explore novel electrode materials with in-depth elucidation of initial coulombic efficiency (ICE), kinetics, and charge storage mechanisms is of great challenge for Na-ion storage. Herein, a novel 3D antiperovskite carbide Ni3ZnC0.7@rGO anode coupled with ether-based electrolyte is reported for fast Na-ion storage, exhibiting superior performance than ester-based electrolyte. Electrochemical tests and density functional theory (DFT) calculations show that Ni3ZnC0.7@rGO anode with ether-based electrolyte can promote charge/ion transport and lower Na+ diffusion energy barrier, thereby improving ICE, reversible capacity, rate, and cycling performance. Cross-sectional-morphology and depth profiling surface chemistry demonstrate that not only a thinner and more homogeneous reaction interface layer with less side effects but also a superior solid electrolyte interface (SEI) film with a high proportion of inorganic components are formed in the ether-based electrolyte, which accelerates Na+ transport and is the significant reason for the improvement of ICE and other electrochemical properties. Meanwhile, electrochemical and ex situ measurements have revealed conversion, alloying, and co-intercalation hybrid mechanisms of the Ni3ZnC0.7@rGO anode based on ether electrolyte. Interestingly, the Na-ion capacitors (SICs) designed by pairing with activated carbon (AC) cathode exhibit favorable electrochemical performance. Overall, this work provides deep insights on developing advanced materials for fast Na-ion storage.
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Developing high electroactivity ruthenium (Ru)-based electrocatalysts for pH-universal hydrogen evolution reaction (HER) is challenging due to the strong bonding strengths of key RuâH/RuâOH intermediates and sluggish water dissociation rates on active Ru sites. Herein, a semi-ionic F-modified N-doped porous carbon implanted with ruthenium nanoclusters (Ru/FNPC) is introduced by a hydrogel sealing-pyrolying-etching strategy toward highly efficient pH-universal hydrogen generation. Benefiting from the synergistic effects between Ru nanoclusters (Ru NCs) and hierarchically F, N-codoped porous carbon support, such synthesized catalyst displays exceptional HER reactivity and durability at all pH levels. The optimal 8Ru/FNPC affords ultralow overpotentials of 17.8, 71.2, and 53.8 mV at the current density of 10 mA cm-2 in alkaline, neutral, and acidic media, respectively. Density functional theory (DFT) calculations elucidate that the F-doped substrate to support Ru NCs weakens the adsorption energies of H and OH on Ru sites and reduces the energy barriers of elementary steps for HER, thus enhancing the intrinsic activity of Ru sites and accelerating the HER kinetics. This work provides new perspectives for the design of advanced electrocatalysts by porous carbon substrate implanted with ultrafine metal NCs for energy conversion applications.
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Ageing has been identified as an independent risk factor for various diseases; however, the physiological basis and molecular changes related to ageing are still largely unknown. Here, we show that the level of APPL2, an adaptor protein, is significantly reduced in the major organs of aged mice. Knocking down APPL2 causes premature ageing of human umbilical vein endothelial cells (HUVECs). We find that a lack of T04C9.1, the homologue of mammalian APPL2, leads to premature ageing, slow movements, lipid deposition, decreased resistance to stresses, and shortened lifespan in Caenorhabditis elegans (C. elegans), which are associated with decreased autophagy. Activating autophagy by rapamycin or inhibition of let-363 suppresses the age-related alternations, impaired motility, and shortened lifespan of C. elegans, which are reversed by knocking down autophagy-related genes. Our work provides evidence that APPL2 and its C. elegans homologue T04C9.1 decrease with age and reveals that a lack of T04C9.1 bridges autophagy decline and ageing in C. elegans.
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Proteínas Adaptadoras Transductoras de Señales , Autofagia , Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Longevidad , Animales , Humanos , Ratones , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Envejecimiento/genética , Envejecimiento Prematuro/genética , Autofagia/genética , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Células Endoteliales de la Vena Umbilical Humana , Longevidad/genéticaRESUMEN
Prostate cancer (PCa) is the second most common malignancy among men globally. The Fu-Zheng-Yi-Liu (FZYL) Formula has been widely utilized in the treatment of PCa. This study investigates whether the FZYL Formula can inhibit PCa by targeting the TAMs/CCL5 pathway. We conducted in vitro co-cultures and in vivo co-injections of PCa cells and TAMs to mimic their interaction. Results showed that the FZYL Formula significantly reduced the proliferation, colony formation, subpopulations of PCSCs, and sphere-formation efficacy of PCa cells, even in the presence of TAM co-culture. Additionally, the Formula markedly decreased the migration, invasion, and epithelial-mesenchymal transition (EMT) of PCa cells induced by TAMs. The FZYL Formula also reversed M2 phenotype polarization in TAMs and dose-dependently reduced their CCL5 expression and secretion, with minimal cytotoxicity observed. Mechanistic studies confirmed that the TAMs/CCL5 axis is a critical target of the FZYL Formula, as the addition of exogenous CCL5 partially reversed the formula's inhibitory effects on PCSCs self-renewal in the co-culture system. Importantly, the Formula also significantly inhibited the growth of PCa xenografts, bone metastasis, and PCSCs activity in vivo by targeting the TAMs/CCL5 pathway. Overall, this study not only elucidates the immunomodulatory mechanism of the FZYL Formula in PCa therapy but also highlights the TAMs/CCL5 axis as a promising therapeutic target.
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Quimiocina CCL5 , Medicamentos Herbarios Chinos , Células Madre Neoplásicas , Neoplasias de la Próstata , Microambiente Tumoral , Macrófagos Asociados a Tumores , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/metabolismo , Masculino , Humanos , Animales , Medicamentos Herbarios Chinos/farmacología , Microambiente Tumoral/efectos de los fármacos , Quimiocina CCL5/metabolismo , Macrófagos Asociados a Tumores/efectos de los fármacos , Macrófagos Asociados a Tumores/metabolismo , Ratones , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/metabolismo , Línea Celular Tumoral , Transición Epitelial-Mesenquimal/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Metástasis de la Neoplasia , Movimiento Celular/efectos de los fármacos , Técnicas de Cocultivo , Ratones DesnudosRESUMEN
Anti-CDK4/6 therapy has been employed for the treatment for head and neck squamous cell carcinoma (HNSCC) with CDK4/6 hyperactivation, but the response rate is relatively low. In this study, we first showed that CDK4 and CDK6 was over-expressed and conferred poor prognosis in HNSCC. Moreover, in RB-positive HNSCC, STAT3 signaling was activated induced by CDK4/6 inhibition and STAT3 promotes RB deficiency by upregulation of MYC. Thirdly, the combination of Stattic and CDK4/6 inhibitor results in striking anti-tumor effect in vitro and in Cal27 derived animal models. Additionally, phospho-STAT3 level negatively correlates with RB expression and predicts poor prognosis in patients with HNSCC. Taken together, our findings suggest an unrecognized function of STAT3 confers to CDK4/6 inhibitors resistance and presenting a promising combination strategy for patients with HNSCC.
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Quinasa 4 Dependiente de la Ciclina , Quinasa 6 Dependiente de la Ciclina , Neoplasias de Cabeza y Cuello , Inhibidores de Proteínas Quinasas , Factor de Transcripción STAT3 , Carcinoma de Células Escamosas de Cabeza y Cuello , Ensayos Antitumor por Modelo de Xenoinjerto , Humanos , Quinasa 4 Dependiente de la Ciclina/antagonistas & inhibidores , Quinasa 6 Dependiente de la Ciclina/antagonistas & inhibidores , Factor de Transcripción STAT3/metabolismo , Animales , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/metabolismo , Neoplasias de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Carcinoma de Células Escamosas de Cabeza y Cuello/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Línea Celular Tumoral , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Transducción de Señal/efectos de los fármacos , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/genética , Femenino , Masculino , Ratones Desnudos , Ratones , Proteína de Retinoblastoma/metabolismo , Proliferación Celular/efectos de los fármacos , Sinergismo Farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Resistencia a Antineoplásicos/efectos de los fármacos , FosforilaciónRESUMEN
STUDY OBJECTIVES: Artificial intelligence (AI) is quickly advancing in the field of sleep medicine, which bodes well for the potential of actual clinical use. In this study, an analysis of the 2nd China Intelligent Sleep Staging Competition was conducted to gain insights into the general level and constraints of AI-assisted sleep staging in China. METHODS: The outcomes of 10 teams from the children's track and 13 teams from the adult track were investigated in this study. The analysis included overall performance, differences between five different sleep stages, variations across subjects, and performance during stage transitions. RESULTS: The adult track's accuracy peaked at 80.46%, while the children's track's accuracy peaked at 88.96%. On average, accuracy rates stood at 71.43% for children and 68.40% for adults. All results were produced within a mere 5-min timeframe. The N1 stage was prone to misclassification as W, N2, and R stages. In the adult track, significant differences were apparent among subjects (p < 0.05), whereas in the children's track, such differences were not observed. Nonetheless, both tracks experienced a performance decline during stage transitions. CONCLUSIONS: The computational speed of AI is remarkably fast, simultaneously holding the potential to surpass the accuracy of physicians. Improving the machine learning model's classification of the N1 stage and transitional periods between stages, along with bolstering its robustness to individual subject variations, is imperative for maximizing its ability in assisting clinical scoring.
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Fases del Sueño , Humanos , China , Fases del Sueño/fisiología , Adulto , Niño , Masculino , Inteligencia Artificial , Femenino , PolisomnografíaRESUMEN
Luminescent chiral Tb-MOF microcrystals with the Tb2(COO)4 subunit indicated strong green mechano-luminescence under compression. Furthermore, piezofluorochromic behavior in the diamond anvil cell was observed, with the intensity tendency of decreasing-increasing-decreasing and a shortened lifetime upon compression, due to the reversible stretchable Tb-Tb interactions. The Tb-Tb distance upon compression was refined through in situ high-pressure X-ray absorption spectra, which was consistent with the tendency of the piezofluorochromic intensity. In situ high-pressure UV-vis absorption spectra, Fourier transform infrared spectra, and powder X-ray diffraction demonstrated the full recovery of Tb-MOF after over 10 GPa compressions due to the semiflexible ligand. This work not only provided an ultrastable Tb-MOF but also illustrated the relationship of the piezofluorochromic behavior with the detailed structural transformation for the first time.