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ABA-insensitive 5 (ABI5) belongs to the basic leucine zipper class of transcription factors and is named for being the fifth identified Arabidopsis mutant unresponsive to ABA. To understand the influence of ABI5 in its active state on downstream gene expression and plant growth and development, we overexpressed the full-length ABI5 (A.t.MX-4) and the active forms of ABI5 with deleted transcriptional repression domains (A.t.MX-1, A.t.MX-2, and A.t.MX-3). Compared with the wild type, A.t.MX-1, A.t.MX-2, and A.t.MX-3 exhibited an increase in rosette leaf number and size, earlier flowering, increased thousand-seed weight, and significantly enhanced drought resistance. Thirty-five upregulated/downregulated proteins in the A.t.MX-1 were identified by proteomic analysis, and these proteins were involved in ABA biosynthesis and degradation, abiotic stress, fatty acid synthesis, and energy metabolism. These proteins participate in the regulation of plant drought resistance, flowering timing, and seed size at the levels of transcription and post-translational modification.
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Second-harmonic-generation (SHG) switching is an emerging phenomenon with potential applications in bistable storage and optical switches while also serving as a sensitive probe for inversion-symmetry. Temperature-induced disorder-order phase transition has been proven to be a rational design strategy for achieving SHG bi-state switching; however, pressure-sensitive SHG switching via a disorder-order structural transition mechanism is rarely reported and lacks sensitivity and cyclicity as practical switching materials. Herein, we demonstrate the pressure-induced "dynamical disorder-order" phase transition as an effective strategy for triggering SHG and SHG switching in NH4Cl. The "dynamical disorder-order" phase transition of NH4Cl occurring at as low as 1 GPa is confirmed by comprehensive in situ high-pressure XRD, molecular vibrational spectra, and Brillouin scattering spectra. The pressure-induced SHG is responsive to a wide excitation wavelength region (800-1500 nm), and the "off-on" switching is reversible for up to 50 cycles, setting a record for pressure-driven switching materials. It is worth noting that when pressure is further increased to 14 GPa, NH4Cl exhibits another SHG "on-off" switching, which makes it the first triplet SHG "off-on-off" switching material. Molecular dynamics simulations reveal the key role of N-H···Cl hydrogen bonding in the pressure-induced "dynamic disorder-order" mechanism. Finally, we verified that chemical pressure and physical pressure can jointly regulate the SHG switching behavior of NH4X (X = Cl, Br). The pressure-driven "dynamic disorder-order" transition mechanism sheds light on the rational design of multistable SHG switching materials for photoswitches and information storage.
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Lithium-ion batteries with transition metal sulfides (TMSs) anodes promise a high capacity, abundant resources, and environmental friendliness, yet they suffer from fast degradation and low Coulombic efficiency. Here, a heterostructured bimetallic TMS anode is fabricated by in situ encapsulating SnS2/MoS2 nanoparticles within an amphiphilic hollow double-graphene sheet (DGS). The hierarchically porous DGS consists of inner hydrophilic graphene and outer hydrophobic graphene, which can accelerate electron/ion migration and strongly hold the integrity of alloy microparticles during expansion and/or shrinkage. Moreover, catalytic Mo converted from lithiated MoS2 can promote the reaction kinetics and suppress heterointerface passivation by forming a building-in-electric field, thereby enhancing the reversible conversion of Sn to SnS2. Consequently, the SnS2/MoS2/DGS anode with high gravimetric and high volumetric capacities achieves 200 cycles with a high initial Coulombic efficiency of >90%, as well as excellent low-temperature performance. When the commercial Li(Ni0.8Co0.1Mn0.1)O2 (NCM811) cathode is paired with the prelithiated SnS2/MoS2/DGS anode, the full cells deliver high gravimetric and volumetric energy densities of 577 Wh kg-1 and 853 Wh L-1, respectively. This work highlights the significance of integrating spatial confinement and atomic heterointerface engineering to solve the shortcomings of conversion-/alloying typed TMS-based anodes to construct outstanding high-energy LIBs.
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Pandan (Pandanus amaryllifolius Roxb.), a member of the Pandanaceae family, has been consumed as food and medicine since ancient times. The current paper provides an overview of the botanical profile, phytochemistry, pharmacology, and applications of P. amaryllifolius. Information regarding P. amaryllifolius was collected from online sources (using PubMed, Science Direct, Google Scholar, Web of Science, ACS, and CNKI) as well as traditional textbooks. Over 100 compounds have been identified, including its characteristic components 2-Acetyl-1-pyrroline and Pandanus alkaloids. Several therapeutic uses of P. amaryllifolius, such as antioxidant, hypoglycemic, antimicrobial, and antitumor activities, have been demonstrated in modern pharmacological studies. Additionally, it could be applied in various fields, including food, energy, material, and the environment. Continued research on P. amaryllifolius can contribute to the development of new drugs and therapies for various diseases. And further studies are needed to improve its utilization.
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Pandanaceae , Fitoquímicos , Fitoquímicos/farmacología , Fitoquímicos/aislamiento & purificación , Estructura Molecular , Pandanaceae/química , Antioxidantes/farmacología , Antioxidantes/aislamiento & purificación , Antioxidantes/química , Humanos , Antiinfecciosos/farmacología , Antiinfecciosos/química , Antiinfecciosos/aislamiento & purificación , Hipoglucemiantes/farmacología , Hipoglucemiantes/química , Alcaloides/farmacología , Alcaloides/aislamiento & purificación , Alcaloides/química , Extractos Vegetales/farmacología , Extractos Vegetales/químicaRESUMEN
Rising global temperatures and critical energy shortages have spurred researches into CO2 fixation and conversion within the realm of energy storage such as Zn-CO2 batteries. However, traditional Zn-CO2 batteries employ double-compartment electrolytic cells with separate carriers for catholytes and anolytes, diverging from the "rocking chair" battery mechanism. The specific energy of these conventional batteries is constrained by the solubility of discharge reactants/products in the electrolyte. Additionally, H2O molecules tend to trigger parasitic reactions at the electrolyte/electrode interfaces, undermining the long-term stability of Zn anodes. In this report, we introduce an innovative "rocking chair" type Zn-CO2 battery that utilizes a weak-acidic zinc trifluoromethanesulfonate aqueous electrolyte compatible with both cathode and anode. This design minimizes side reactions on the Zn surface and leverages the high catalytic activity of the cathode material, allowing the battery to achieve a substantial discharge capacity of 6734â mAh g-1 and maintain performance over 65â cycles. Moreover, the successful production of pouch cells demonstrates the practical applicability of Zn-CO2 batteries. Electrode characterizations confirm superior electrochemical reversibility, facilitated by solid discharge products of ZnCO3 and C. This work advances a "rocking chair" Zn-CO2 battery with an enhanced specific energy and a reversible pathway, providing a foundation for developing high-performance metal-CO2 batteries.
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This Data in Brief (DiB) article presents the differences in cycling behaviors related to violations, errors, and positive behaviors by region. The study data were collected by means of a structured questionnaire applied to a full sample of 7,001 participants from 19 countries, distributed over 5 continents. This paper proposes descriptive statistics, as well as common statistical tests. The aim is to enable authors to make their own analyses, not to provide precise interpretations. For further information about the macro project supporting the collection of these data, it is advised to refer to the paper titled "Cross-culturally approaching the cycling behavior questionnaire (CBQ): Evidence from 19 countries", published in Transportation Research Part F: Traffic Psychology and Behavior.
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BACKGROUND: The purpose of this study was to evaluate the efficacy and safety of fruquintinib-based therapy as a salvage therapy for patients with advanced or metastatic sarcoma, including soft tissue sarcoma (STS) and bone sarcoma. METHODS: Patients with advanced or metastatic sarcoma were divided into two groups. One group received fruquintinib monotherapy, while the other received fruquintinib combined therapy. Safety and efficacy of fruquintinib-based therapy were recorded and reviewed retrospectively, including progression-free survival (PFS), overall response rate (ORR), and adverse events (AEs). RESULTS: Between August 2021 and December 2022, 38 sarcoma patients were retrospectively included. A total of 14 patients received fruquintinib alone (including 6 STS and 8 bone sarcoma), while 24 were treated with fruquintinib combined therapy (including 2 STS and 22 bone sarcoma). The median follow-up was 10.2 months (95% CI, 6.4-11.5). For the entire population, the median PFS was 8.0 months (95% CI, 5.5-13.0). The ORR was 13.1%, while the disease control rate (DCR) was 86.8%. The univariate analysis showed that radiotherapy history (HR, 4.56; 95% CI, 1.70-12.24; p = 0.003), bone sarcoma (HR, 0.34; 95% CI, 0.14-0.87; p = 0.024), and treatment method of fruquintinib (HR, 0.36; 95% CI, 0.15-0.85; p = 0.021) were significantly associated with PFS. The multivariate analysis showed that patients without radiotherapy history were associated with a better PFS (HR, 3.71; 95% CI: 1.31-10.55; p = 0.014) than patients with radiotherapy history. Patients in combination group reported pneumothorax (8.3%), leukopenia (33.3%), thrombocytopenia (12.5%), diarrhea (4.2%), and anemia (4.2%) as the most frequent grade 3 or higher treatment-emergent AEs (TEAEs), while there was no severe TEAEs occurred in the monotherapy group. CONCLUSIONS: Fruquintinib-based therapy displayed an optimal tumor control and an acceptable safety profile in patients with advanced or metastatic sarcoma.
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Benzofuranos , Neoplasias Óseas , Quinazolinas , Sarcoma , Humanos , Femenino , Sarcoma/tratamiento farmacológico , Sarcoma/mortalidad , Sarcoma/patología , Masculino , Persona de Mediana Edad , Adulto , Estudios Retrospectivos , Quinazolinas/uso terapéutico , Quinazolinas/efectos adversos , Anciano , Benzofuranos/uso terapéutico , Benzofuranos/efectos adversos , Neoplasias Óseas/secundario , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/mortalidad , Adulto Joven , Terapia Recuperativa , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Supervivencia sin Progresión , Adolescente , Resultado del TratamientoRESUMEN
BACKGROUND: New daily persistent headache (NDPH) is a rare primary headache with unclear pathogenesis. Neuroimaging studies of NDPH are limited, and controversy still exists. Diffusion tensor imaging (DTI) is commonly used to study the white matter. However, lacking specificity, the potential pathological mechanisms of white matter microstructural changes remain poorly understood. In addition, the intricacy of gray matter structures impedes the application of the DTI model. Here, we applied an advanced diffusion model of neurite orientation dispersion and density imaging (NODDI) to study the white matter and cortical gray matter microstructure in patients with NDPH. METHODS: This study assessed brain microstructure, including 27 patients with NDPH, and matched 28 healthy controls (HCs) by NODDI. The differences between the two groups were assessed by tract-based spatial statistics (TBSS) and surface-based analysis (SBA), focusing on the NODDI metrics (neurite density index (NDI), orientation dispersion index (ODI), and isotropic volume fraction (ISOVF)). Furthermore, we performed Pearson's correlation analysis between the NODDI indicators and clinical characteristics. RESULTS: Compared to HCs, patients with NDPH had a reduction of density and complexity in several fiber tracts. For robust results, the fiber tracts were defined as comprising more than 100 voxels, including bilateral inferior fronto-occipital fasciculus (IFOF), left superior longitudinal fasciculus (SLF) and inferior longitudinal fasciculus (ILF), as well as right corticospinal tract (CST). Moreover, the reduction of neurite density was uncovered in the left superior and middle frontal cortex, left precentral cortex, and right lateral orbitofrontal cortex and insula. There was no correlation between the NODDI metrics of these brain regions and clinical variables or scales of relevance after the Bonferroni correction. CONCLUSIONS: Our research indicated that neurite loss was detected in both white matter and cortical gray matter of patients with NDPH.
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Imagen de Difusión Tensora , Sustancia Gris , Sustancia Blanca , Humanos , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología , Femenino , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/patología , Masculino , Adulto , Persona de Mediana Edad , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/patología , Trastornos de Cefalalgia/diagnóstico por imagen , Trastornos de Cefalalgia/patología , Neuritas/patologíaRESUMEN
OBJECTIVES: Delirium is a significant health concern in acute stroke patients. We aim to systematically summarize existing evidence to conduct a meta-analysis to quantify the occurrence and risk factors for delirium after acute stroke. METHOD: PubMed, EMBASE and MEDLINE were searched from inception to Feb. 2023 for prospective observational studies that reported the incidence or prevalence of post-stroke delirium and/or evaluated potential risk factors. The search strategy was created using controlled vocabulary terms and text words for stroke and delirium. We performed a meta-analysis of the estimates for occurrence and risk factors using random-effects models. Meta-regression and subgroup meta-analyses were conducted to explore the sources of heterogeneity. Study quality and quality of evidence were assessed using the customized Newcastle-Ottawa Scale and GRADE, respectively. RESULTS: Forty-nine studies that enrolled 12383 patients were included. The pooled occurrence rate of post-stroke delirium was 24.4â¯% (95â¯%CI, 20.4â¯%-28.9â¯%, I2=96.2â¯%). The pooled occurrence of hyperactive, hypoactive, and mixed delirium was 8.5â¯%, 5.7â¯% and 5.0â¯%, respectively. Study location, delirium assessment method and stroke type independently affected the heterogeneity of the pooled estimate of delirium. Statistically significant risk factors were older age, low education level, cigarette smoking, alcohol drinking, atrial fibrillation, lower ADL level, higher pre-stroke mRS score, premorbid cognitive impairment or dementia, aphasia, total anterior circulation impairment, higher National Institute of Health Stroke Scale score and infection. CONCLUSIONS: Delirium affected 1 in 4 acute stroke patients, although reported rates may depend on assessment method and stroke type. Timely prevention, recognition and intervention require prioritizing patients with dominant risk factors.
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Zn-I2 flow batteries, with a standard voltage of 1.29 V based on the redox potential gap between the Zn2+-negolyte (-0.76 vs. SHE) and I2-posolyte (0.53 vs. SHE), are gaining attention for their safety, sustainability, and environmental-friendliness. However, the significant growth of Zn dendrites and the formation of dead Zn generally prevent them from being cycled at high current density (>80 mA cm-2). In addition, the crossover of Zn2+ across cation-exchange-membrane also limits their cycle stability. Herein, we propose a chelated Zn(P2O7)26- (donated as Zn(PPi)26-) negolyte, which facilitates dendrite-free Zn plating and effectively prevents Zn2+ crossover. Remarkably, the utilization of chelated Zn(PPi)26- as a negolyte shifts the Zn2+/Zn plating/stripping potential to -1.08 V (vs. SHE), increasing cell voltage to 1.61 V. Such high voltage Zn-I2 flow battery shows a promising stability over 250 cycles at a high current density of 200 mA cm-2, and a high power density up to 606.5 mW cm-2.
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Sodium-ion batteries (SIBs) have undergone rapid development as a complementary technology to lithium-ion batteries due to abundant sodium resources. However, the extended charging time and low energy density pose a significant challenge to the widespread use of SIBs in electric vehicles. To overcome this hurdle, there is considerable focus on developing fast-charging anode materials with rapid Na⺠diffusion and superior reaction kinetics. Here, the key factors that limit the fast charging of anode materials are examined, which provides a comprehensive overview of the major advances and fast-charging characteristics across various anode materials. Specifically, it systematically dissects considerations to enhance the rate performance of anode materials, encompassing aspects such as porous engineering, electrolyte desolvation strategies, electrode/electrolyte interphase, electronic conductivity/ion diffusivity, and pseudocapacitive ion storage. Finally, the direction and prospects for developing fast-charging anode materials of SIBs are also proposed, aiming to provide a valuable reference for the further advancement of high-power SIBs.
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One of the fundamental techniques in genetic engineering is the creation of Escherichia coli competent cells using the CaCl2 method. However, little is known about the mechanism of E. coli competence formation. We have previously found that the cspA gene may play an indispensable role in the preparation of E. coli DH5α competent cells through multiomics analysis. In the present study, the cellular localization, physicochemical properties, and function of the protein expressed by the cspA gene were analyzed. To investigate the role of the cspA gene in E. coli transformation, cspA-deficient mutant was constructed by red homologous recombination. The growth, transformation efficiency, and cell morphology of the cspA-deficient strain and E. coli were compared. It was found that there were no noticeable differences in growth and morphology between E. coli and the cspA-deficient strain cultured at 37°C, but the mutant exhibited increased transformation efficiencies compared to E. coli DH5α for plasmids pUC19, pET-32a, and p1304, with enhancements of 2.23, 2.24, and 3.46 times, respectively. It was proved that cspA gene is an important negative regulatory gene in the CaCl2 preparation of competent cells.
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Cloruro de Calcio , Proteínas de Escherichia coli , Escherichia coli , Plásmidos , Transformación Bacteriana , Escherichia coli/genética , Escherichia coli/crecimiento & desarrollo , Escherichia coli/metabolismo , Cloruro de Calcio/metabolismo , Cloruro de Calcio/farmacología , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Plásmidos/genética , Ingeniería Genética/métodos , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Recombinación HomólogaRESUMEN
OBJECTIVE: To investigate the serum lipid profiles of patients with localized osteosarcoma around the knee joint before and after neoadjuvant chemotherapy. METHODS: After retrospectively screening the data of 742 patients between January 2007 and July 2020, 50 patients aged 13 to 39 years with Enneking stage II disease were included in the study. Serum lipid levels, including total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), lipoprotein-α [Lp(a)], and apolipoprotein A1, B, and E (ApoA1, ApoB, and ApoE), and clinicopathological characteristics were collected before and after neoadjuvant chemotherapy. RESULTS: The mean levels of TC, TG, and ApoB were significantly increased following neoadjuvant chemotherapy (16%, 38%, and 20%, respectively, vs. pretreatment values; P<0.01). The mean levels of LDL-C and ApoE were also 19% and 16% higher, respectively (P<0.05). No correlation was found between the pretreatment lipid profile and the histologic response to chemotherapy. An increase in Lp(a) was strongly correlated with the Ki-67 index (R=0.31, P=0.023). Moreover, a trend toward longer disease-free survival (DFS) was observed in patients with decreased TG and increased LDL-C following chemotherapy, although this difference was not statistically significant (P=0.23 and P=0.24, respectively). CONCLUSION: Significant elevations in serum lipids were observed after neoadjuvant chemotherapy in patients with localized osteosarcoma. There was no prognostic significance of pretreatment serum lipid levels on histologic response to neoadjuvant chemotherapy. The scale of increase in serum Lp(a) might have a potential prognostic role in osteosarcoma. Patients with increased LDL-C or reduced TG after chemotherapy seem to exhibit a trend toward favorable DFS.
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Articulación de la Rodilla , Lípidos , Lipoproteínas , Terapia Neoadyuvante , Osteosarcoma , Humanos , Osteosarcoma/tratamiento farmacológico , Osteosarcoma/sangre , Osteosarcoma/patología , Masculino , Femenino , Estudios Retrospectivos , Adolescente , Adulto , Lípidos/sangre , Adulto Joven , Articulación de la Rodilla/patología , Lipoproteínas/sangre , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/sangreRESUMEN
BACE1, a crucial enzyme in the amyloid-ß deposition theory of Alzheimer's disease (AD), is targeted by Codonopsis pilosula, a traditional tonic believed to impede AD onset. However, the specific active compounds responsible for its effects remain elusive. Our prior network pharmacology research identified C. pilosula polysaccharides (CPPS) and Lobetyolin may serve as potential inhibitors of AD by suppressing amyloidogenesis. Here, we recombinantly expressed BACE1 under varied conditions and assessed its activity using Fluorescence Resonance Energy Transfer technology. Through spectroscopy, molecular docking, and dynamics, we elucidated the interactions of CPPS, Lobetyolin, and BACE1. Optimal BACE1 expression occurred at 22⯰C with 0.4â¯mM IPTG for 6â¯h, yielding a 72â¯kDa protein. Enzyme kinetics displayed a maximum rate of 4096⯵mol/min and a Michaelis constant of 16â¯mg/mL for BACE1. Spectroscopic analysis revealed differing binding affinities of the compounds at various temperatures, peaking at 293â¯K. Lobetyolin exhibited superior binding to BACE1 compared to CPPS, driven by hydrophobic and electrostatic forces. Molecular docking and dynamics highlighted hydrophobic amino acids' role in BACE1 interactions with Lobetyolin and CPPS, with binding energy < -1.2â¯kcal/mol signifying strong affinities. Notably, Lobetyolin and CPPS showed higher BACE1 affinity than APP, with the Lobetyolin-BACE1 complex being the most stable.
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Secretasas de la Proteína Precursora del Amiloide , Ácido Aspártico Endopeptidasas , Codonopsis , Simulación del Acoplamiento Molecular , Polisacáridos , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Secretasas de la Proteína Precursora del Amiloide/genética , Ácido Aspártico Endopeptidasas/metabolismo , Ácido Aspártico Endopeptidasas/genética , Ácido Aspártico Endopeptidasas/química , Humanos , Codonopsis/química , Polisacáridos/química , Polisacáridos/metabolismo , Cinética , Unión Proteica , Expresión Génica , Simulación de Dinámica Molecular , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/químicaRESUMEN
Jingzhi Guanxin Oral Liquids (JZGX), a traditional Chinese medicine formulation prepared from the decoction of five herbs, has been utilized to relieve chest pain with coronary artery disease (CAD). However, the chemical composition and therapeutic mechanisms of JZGX remain obscured. In this research, the potential targets and pathways of JZGX against CAD were anticipated through network pharmacology based on analyzing its chemical constituents using UPLC-Q-TOF-MS/MS. One hundred seven ingredients in JZGX were identified. The 39 active chemicals and 37 key targets were screened, and CAD-related signaling pathways were clustered, mainly associated with lipid metabolism. Subsequently, the atherosclerotic CAD animal model employing 24 weeks of high-fat diet (HFD) ApoE-/- mice was constructed to investigate the JZGX efficacy and underlying mechanisms validating network forecasts. The histological staining examination and cardiovascular biomarker tests confirmed that JZGX reduced plaque formation in the aorta and decreased blood lipids in vivo. It featured anti-inflammatory, anti-thrombotic, and myocardial protective effects. JZGX prevented excessive lipid deposits and inflammation within the liver and exhibited hepatoprotective properties. Serum untargeted metabolomics analysis indicated that JZGX ameliorated metabolic abnormalities in atherosclerotic CAD mice and prompted lipid metabolism, especially linoleic acid. The PPARs and attached critical targets (SREBP1, FASN, PTGS2, and CYP3A), filtered from the networks and connected with lipid metabolism, were dramatically modulated through JZGX administration, as revealed by western blotting. The molecular docking outcomes showed that all 39 active ingredients in JZGX had good binding activity with PPARα and PPARγ. These findings illustrate that JZGX alleviates atherosclerotic CAD progression by remodeling the lipid metabolism and regulating PPAR-related proteins.
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The precision of short-term photovoltaic power forecasts is of utmost importance for the planning and operation of the electrical grid system. To enhance the precision of short-term output power prediction in photovoltaic systems, this paper proposes a method integrating K-means clustering: an improved snake optimization algorithm with a convolutional neural network-bidirectional long short-term memory network to predict short-term photovoltaic power. Firstly, K-means clustering is utilized to categorize weather scenarios into three categories: sunny, cloudy, and rainy. The Pearson correlation coefficient method is then utilized to determine the inputs of the model. Secondly, the snake optimization algorithm is improved by introducing Tent chaotic mapping, lens imaging backward learning, and an optimal individual adaptive perturbation strategy to enhance its optimization ability. Then, the multi-strategy improved snake optimization algorithm is employed to optimize the parameters of the convolutional neural network-bidirectional long short-term memory network model, thereby augmenting the predictive precision of the model. Finally, the model established in this paper is utilized to forecast photovoltaic power in diverse weather scenarios. The simulation findings indicate that the regression coefficients of this method can reach 0.99216, 0.95772, and 0.93163 on sunny, cloudy, and rainy days, which has better prediction precision and adaptability under various weather conditions.
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Patient-derived organoids (PDOs) have emerged as a promising platform for clinical and translational studies. A strong correlation exists between clinical outcomes and the use of PDOs to predict the efficacy of chemotherapy and/or radiotherapy. To standardize interpretation and enhance scientific communication in the field of cancer precision medicine, we revisit the concept of PDO-based drug sensitivity testing (DST). We present an expert consensus-driven approach for medication selection aimed at predicting patient responses. To further standardize PDO-based DST, we propose guidelines for clarification and characterization. Additionally, we identify several major challenges in clinical prediction when utilizing PDOs.
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Antineoplásicos , Consenso , Desarrollo de Medicamentos , Neoplasias , Organoides , Medicina de Precisión , Organoides/efectos de los fármacos , Humanos , Medicina de Precisión/métodos , Neoplasias/tratamiento farmacológico , Desarrollo de Medicamentos/métodos , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Ensayos de Selección de Medicamentos Antitumorales/métodosRESUMEN
PURPOSE: Anemia is relatively common in cancer patients, and is associated with poor survival in patients with various malignancies. However, how anemia would affect prognosis and response to neoadjuvant chemotherapy (NAC) in osteosarcoma (OS) is still without substantial evidence. METHODS: We retrospectively analysed 242 patients with stage II OS around the knee joint in our institute. Changed hemoglobin (Hb) levels (before and after NAC) were recorded to assess the prognostic value in DFS (disease-free survival) and tumor response to NAC. Univariate and multivariate analyses were conducted to identify prognostic factors related with outcome in OS patients. RESULTS: The mean Hb level significantly decreased after NAC (134.5 ± 15.3 g/L vs. 117.4 ± 16.3 g/L). The percentage of mild (21%), moderate (4.2%) and severe (0%) anemia patients markedly increased after NAC: 41%, 24% and 4.1% respectively. There was higher percentage of ≥ 5% Hb decline in patients with tumor necrosis rate < 90% (141 out of 161), compared with those with tumor necrosis rate ≥ 90% (59 out of 81). Further univariate and survival analysis demonstrated that Hb decline had a significant role in prediction survival in OS patients. Patients with ≥ 5% Hb decline after NAC had an inferior DFS compared with those with < 5% Hb decline. CONCLUSION: In osteosarcoma, patients with greater Hb decrease during neoadjuvant treatment were shown to have worse DFS and a poorer response to NAC than those without. Attempts to correct anemia and their effects on outcomes for osteosarcoma patients should be explored in future studies.