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1.
Brief Bioinform ; 25(5)2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-39120644

RESUMEN

Recent advancements in spatial imaging technologies have revolutionized the acquisition of high-resolution multichannel images, gene expressions, and spatial locations at the single-cell level. Our study introduces xSiGra, an interpretable graph-based AI model, designed to elucidate interpretable features of identified spatial cell types, by harnessing multimodal features from spatial imaging technologies. By constructing a spatial cellular graph with immunohistology images and gene expression as node attributes, xSiGra employs hybrid graph transformer models to delineate spatial cell types. Additionally, xSiGra integrates a novel variant of gradient-weighted class activation mapping component to uncover interpretable features, including pivotal genes and cells for various cell types, thereby facilitating deeper biological insights from spatial data. Through rigorous benchmarking against existing methods, xSiGra demonstrates superior performance across diverse spatial imaging datasets. Application of xSiGra on a lung tumor slice unveils the importance score of cells, illustrating that cellular activity is not solely determined by itself but also impacted by neighboring cells. Moreover, leveraging the identified interpretable genes, xSiGra reveals endothelial cell subset interacting with tumor cells, indicating its heterogeneous underlying mechanisms within complex cellular interactions.


Asunto(s)
Análisis de la Célula Individual , Análisis de la Célula Individual/métodos , Humanos , Algoritmos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Biología Computacional/métodos
2.
EMBO Rep ; 25(3): 971-990, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38279020

RESUMEN

Tumor metastasis involves cells migrating directionally in response to external chemical signals. Reactive oxygen species (ROS) in the form of H2O2 has been demonstrated as a chemoattractant for neutrophils but its spatial characteristics in tumor microenvironment and potential role in tumor cell dissemination remain unknown. Here we investigate the spatial ROS distribution in 3D tumor spheroids and identify a ROS concentration gradient in spheroid periphery, which projects into a H2O2 gradient in tumor microenvironment. We further reveal the role of H2O2 gradient to induce chemotaxis of tumor cells by activating Src and subsequently inhibiting RhoA. Finally, we observe that the absence of mitochondria cristae remodeling proteins including the mitochondria-localized actin motor Myosin 19 (Myo19) enhances ROS gradient and promotes tumor dissemination. Myo19 downregulation is seen in many tumors, and Myo19 expression is negatively associated with tumor metastasis in vivo. Together, our study reveals the chemoattractant role of tumor microenvironmental ROS and implies the potential impact of mitochondria cristae disorganization on tumor invasion and metastasis.


Asunto(s)
Quimiotaxis , Peróxido de Hidrógeno , Especies Reactivas de Oxígeno , Miosinas/metabolismo , Factores Quimiotácticos
3.
Br J Cancer ; 2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-38997407

RESUMEN

BACKGROUND: Sarcomas are diverse neoplasms with highly variable histological appearances in which diagnosis is often challenging and management options for metastatic/unresectable disease limited. Many sarcomas have distinctive molecular alterations, but the range of alterations is large, variable in type and rapidly increasing, meaning that testing by limited panels is unable to capture the broad spectrum of clinically pertinent genomic drivers required. Paired whole genome sequencing (WGS) in contrast allows comprehensive assessment of small variants, copy number and structural variants along with mutational signature analysis and germline testing. METHODS: Introduction of WGS as a diagnostic standard for all eligible patients with known or suspected soft tissue sarcoma over a 2-year period at a soft tissue sarcoma treatment centre. RESULTS: WGS resulted in a refinement in the diagnosis in 37% of cases, identification of a target for personalised therapy in 33% of cases, and a germline alteration in 4% of cases. CONCLUSION: Introduction of WGS poses logistical and training challenges, but offers significant benefits to this group of patients.

4.
Small ; 20(28): e2309750, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38299490

RESUMEN

Nanoarchitectonics of semiconductors shed light on efficient photocatalytic hydrogen evolution by precisely controlling the surface microenvironment of cocatalysts. Taking cadmium zinc sulfide (CZS) nanoparticles as a target, the spontaneous modifications are conducted by interactions between surface Cd2+/Zn2+ atoms and thiol groups in thioglycolic acid. The capping ligand impacts the semiconductor surface with a negative electronic environment, contributing to the full coverage of CZS by nickel-cobalt hydroxides (NiCo-LDHs) cocatalysts. The obtained core-shell CZS@NiCo-LDHs, possessing a shell thickness of ≈20 nm, exhibits a distinguished topology (SBET = 87.65m2 g-1), long surface carrier lifetime, and efficient charge-hole separation. Further photocatalytic hydrogen evaluation demonstrates an enhanced H2 evolution rate of 18.75 mmol g-1 h-1 with an apparent quantum efficiency of 16.3% at 420 nm. The recorded catalytic performance of the core-shell sample is 44.6 times higher than that of pure CZS nanospheres under visible light irradiation. Further density functional theory simulations indicate that sulfur atoms play the role of charge acceptor and surface Ni/Co atoms are electron donors, as well as a built-in electric field effect can be established. Altogether, this work takes advantage of strong S affinity from surface metal atoms, revealing the interfacial engineering toward improved visible-light-driven photocatalytic hydrogen evolution (PHE) activity.

5.
Opt Lett ; 49(7): 1664-1667, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38560831

RESUMEN

High-power all-solid-state continuous-wave (CW) single-frequency laser with high linear polarization is a significant source for quantum optics and precision measurement. In this Letter, a high-power linearly polarized CW single-frequency laser based on the single-crystal fiber (SCF) master-oscillator power amplifier (MOPA) is presented, in which a homemade 140 W low-noise CW single-frequency laser and a Nd:YAG SCF are firstly employed as the seed laser and the medium of the MOPA, respectively. The mode-matching between the pump laser propagated with waveguide form and the freely propagated seed laser is optimized by considering the influence of the degradations of the polarization and the beam quality. Finally, when the incident powers of the pump and seed lasers are 262.6 W and 126.3 W, respectively, the seed waist radius is optimized to 200 µm. In this case, the output power of the linearly polarized laser reaches up to 208 W, which is the highest output power, to the best of our knowledge. The presented results provide a good reference for implementing a high power and high degree of the polarization and good beam quality laser based on the SCF MOPA.

6.
Opt Lett ; 49(14): 4014-4017, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39008765

RESUMEN

An all-solid-state single-frequency continuous-wave (CW) 355 nm ultraviolet (UV) laser based on a dispersion-compensated doubly resonant resonator is presented in this Letter that is achieved by employing homemade high-stability all-solid-state frequency-correlated dual-wavelength lasers at 1064 and 532 nm and a temperature-controlled type-I critical-phase-matching LiB3O5 (LBO) to act as the fundamental laser source and the nonlinear medium, respectively. The frequency-correlated dual-wavelength single-frequency CW laser supplies the fundamental frequency 1064 and 532 nm lasers with good frequency synchronization. And the temperature-controlled LBO acts as the dispersion-compensation element to realize double resonance of the 1064 and 532 nm laser. Finally, a 4.2 W high-stability 355 nm UV laser is experimentally obtained, and the corresponding total conversion efficiency is up to 20.5%. To the best of our knowledge, this is the highest power reported about single-frequency CW 355 nm UV laser. The presented method can pave a way to develop a compact single-frequency 355 nm UV laser with high output power.

7.
BMC Cancer ; 24(1): 600, 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38760805

RESUMEN

PURPOSE: Exercise-based cancer rehabilitation via digital technologies can provide a promising alternative to centre-based exercise training, but data for cancer patients and survivors are limited. We conducted a meta-analysis examining the effect of telehealth exercise-based cancer rehabilitation in cancer survivors on cardiorespiratory fitness, physical activity, muscle strength, health-related quality of life, and self-reported symptoms. METHODS: PubMed, Web of Science, and reference lists of articles related to the aim were searched up to March 2023. Randomized controlled clinical trials were included comparing the effect of telehealth exercise-based cancer rehabilitation with guideline-based usual care in adult cancer survivors. The primary result was cardiorespiratory fitness expressed by peak oxygen consumption. RESULTS: A total of 1510 participants were identified, and ten randomized controlled trials (n = 855) were included in the meta-analysis. The study sample was 85% female, and the mean age was 52.7 years. Meta-analysis indicated that telehealth exercise-based cancer rehabilitation significantly improved cardiorespiratory fitness (SMD = 0.34, 95% CI 0.20, 0.49, I2 = 42%, p < 0.001) and physical activity (SMD = 0.34, 95% CI, 0.17, 0.51, I2 = 71%, p < 0.001). It was uncertain whether telehealth exercise-based cancer rehabilitation, compared with guideline-based usual care, improved the quality of life (SMD = 0.23, 95%CI, -0.07, 0.52, I2 = 67%, p = 0.14) body mass index (MD = 0.46, 95% CI, -1.19, 2.12, I2 = 60%, p = 0.58) and muscle strength (SMD = 0.07, 95% CI, -0.14, 0.28, I2 = 37%, p = 0.51). CONCLUSION: This meta-analysis showed that telehealth exercise cancer rehabilitation could significantly increase cardiorespiratory fitness and physical activity levels and decrease fatigue. It is uncertain whether these interventions improve quality of life and muscle strength. High-quality and robust studies are needed to investigate specific home-based exercise regimens in different cancer subgroups to increase the certainty of the evidence.


Asunto(s)
Capacidad Cardiovascular , Terapia por Ejercicio , Fuerza Muscular , Neoplasias , Calidad de Vida , Humanos , Neoplasias/rehabilitación , Terapia por Ejercicio/métodos , Femenino , Supervivientes de Cáncer , Ensayos Clínicos Controlados Aleatorios como Asunto , Telemedicina , Masculino , Ejercicio Físico , Persona de Mediana Edad , Telerrehabilitación
8.
Exp Eye Res ; 238: 109751, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-38097101

RESUMEN

Choroidal neovascularization (CNV) is the primary pathogenic process underlying wet age-related macular degeneration, leading to severe vision loss. Despite current anti-vascular endothelial growth factor (VEGF) therapies, several limitations persist. Crocetin, a major bioactive constituent of saffron, exhibits multiple pharmacological activities, yet its role and mechanism in CNV remain unclear. Here, we investigated the potential effects of crocetin on CNV using in vitro and in vivo models. In human umbilical vein endothelial cells, crocetin demonstrated inhibition of VEGF-induced cell proliferation, migration, and tube formation in vitro, as assessed by CCK-8 and EdU assays, transwell and scratch assays, and tube formation analysis. Additionally, crocetin suppressed choroidal sprouting in ex vivo experiments. In the human retinal pigment epithelium (RPE) cell line ARPE-19, crocetin attenuated cobalt chloride-induced hypoxic cell injury, as evidenced by CCK-8 assay. As evaluated by quantitative PCR and Western blot assay, it also reduced hypoxia-induced expression of VEGF and hypoxia-inducible factor 1α (HIF-1α), while enhancing zonula occludens-1 expression. In a laser-induced CNV mouse model, intravitreal administration of crocetin significantly reduced CNV size and suppressed elevated expressions of VEGF, HIF-1α, TNFα, IL-1ß, and IL-6. Moreover, crocetin treatment attenuated the elevation of phospho-S6 in laser-induced CNV and hypoxia-induced RPE cells, suggesting its potential anti-angiogenic effects through antagonizing the mechanistic target of rapamycin complex 1 (mTORC1) signaling. Our findings indicate that crocetin may hold promise as an effective drug for the prevention and treatment of CNV.


Asunto(s)
Neovascularización Coroidal , Células Endoteliales , Ratones , Animales , Humanos , Células Endoteliales/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Sincalida/metabolismo , Neovascularización Coroidal/tratamiento farmacológico , Neovascularización Coroidal/prevención & control , Neovascularización Coroidal/metabolismo , Hipoxia/metabolismo , Modelos Animales de Enfermedad , Epitelio Pigmentado de la Retina/metabolismo
9.
Artículo en Inglés | MEDLINE | ID: mdl-38591775

RESUMEN

A Gram-stain-negative, aerobic, rod-shaped and halotolerant bacterium, designated as strain ASW11-75T, was isolated from intertidal sediments in Qingdao, PR China, and identified using a polyphasic taxonomic approach. Growth of strain ASW11-75T occurred at 10-45 °C (optimum, 37 °C), pH 6.5-9.0 (optimum, pH 8.0) and 0.5-18.0 % NaCl concentrations (optimum, 2.5 %). Phylogenetic analyses based on 16S rRNA gene sequences and 1179 single-copy orthologous clusters indicated that strain ASW11-75T is affiliated with the genus Marinobacter. Strain ASW11-75T showed highest 16S rRNA gene sequence similarity to 'Marinobacter arenosus' CAU 1620T (98.5 %). The digital DNA-DNA hybridization and average nucleotide identity values between strain ASW11-75T and its closely related strains (Marinobacter salarius R9SW1T, Marinobacter similis A3d10T, 'Marinobacter arenosus' CAU 1620T, Marinobacter sediminum R65T, Marinobacter salinus Hb8T, Marinobacter alexandrii LZ-8T and Marinobacter nauticus ATCC 49840T) were 19.8-24.5 % and 76.6-80.7 %, respectively. The predominant cellular fatty acids were C16 : 0, C18 : 1 ω9c and C16 : 0 N alcohol. The polar lipids were phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, one unidentified aminophospholipid and two unidentified lipids. The major isoprenoid quinone was ubiquinone-9. The genomic DNA G+C content was 62.2 mol%. Based on genomic and gene function analysis, strain ASW11-75T had lower protein isoelectric points with higher ratios of acidic residues to basic residues and possessed genes related to ion transport and organic osmoprotectant uptake, implying its potential tolerance to salt. The results of polyphasic characterization indicated strain ASW11-75T represents a novel Marinobacter species, for which the name Marinobacter qingdaonensis sp. nov. with the type strain ASW11-75T is proposed. The type strain is ASW11-75T (=KCTC 82497T=MCCC 1K05587T).


Asunto(s)
Ácidos Grasos , Marinobacter , Ácidos Grasos/química , Fosfolípidos/química , Agua de Mar/microbiología , Filogenia , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Composición de Base , ADN Bacteriano/genética , Técnicas de Tipificación Bacteriana
10.
Artículo en Inglés | MEDLINE | ID: mdl-38995188

RESUMEN

A Gram-negative, ellipsoidal to short-rod-shaped, motile bacterium was isolated from Beijing's urban air. The isolate exhibited the closest kinship with Noviherbaspirillum aerium 122213-3T, exhibiting 98.4 % 16S rRNA gene sequence similarity. Phylogenetic analyses based on 16S rRNA gene sequences and genomes showed that it clustered closely with N. aerium 122213-3T, thus forming a distinct phylogenetic lineage within the genus Noviherbaspirillum. The average nucleotide identity and digital DNA-DNA hybridization values between strain I16B-00201T and N. aerium 122213-3T were 84.6 and 29.4 %, respectively. The respiratory ubiquinone was ubiquinone 8. The major fatty acids (>10 %) were summed feature 3 (C16:1ω6c/C16:1ω7c, 43.3 %), summed feature 8 (C18:1ω7c/C18:1ω6c, 15.9 %) and C12:0 (11.0 %). The polyamine profile showed putrescine as the predominant compound. The polar lipid profile consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, unknown lipids and unknown phosphatidylaminolipids. The phenotypic, phylogenetic and chemotaxonomic results consistently supported that strain I16B-00201T represented a novel species of the genus Noviherbaspirillum, for which the name Noviherbaspirillum album sp. nov. is proposed, with I16B-00201T (=CPCC 100848T=KCTC 52095T) designated as the type strain. Its DNA G+C content is 59.4 mol%. Pan-genome analysis indicated that some Noviherbaspirillum species possess diverse nitrogen and aromatic compound metabolism pathways, suggesting their potential value in pollutant treatment.


Asunto(s)
Microbiología del Aire , Técnicas de Tipificación Bacteriana , Composición de Base , ADN Bacteriano , Ácidos Grasos , Hibridación de Ácido Nucleico , Fosfolípidos , Filogenia , ARN Ribosómico 16S , Análisis de Secuencia de ADN , Ubiquinona , ARN Ribosómico 16S/genética , Beijing , ADN Bacteriano/genética , Ácidos Grasos/análisis , Fosfolípidos/análisis
11.
Diabetes Obes Metab ; 26(4): 1395-1406, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38287130

RESUMEN

AIM: Novel long-acting drugs for type 2 diabetes mellitus may optimize patient compliance and glycaemic control. Exendin-4-IgG4-Fc (E4F4) is a long-acting glucagon-like peptide-1 receptor agonist. This first-in-human study investigated the safety, tolerability, pharmacokinetic, pharmacodynamic and immunogenicity profiles of a single subcutaneous injection of E4F4 in healthy subjects. METHODS: This single-centre, randomized, double-blind, placebo-controlled phase 1 clinical trial included 96 subjects in 10 sequential cohorts that were provided successively higher doses of E4F4 (0.45, 0.9, 1.8, 3.15, 4.5, 6.3, 8.1, 10.35, 12.6 and 14.85 mg) or placebo (ChinaDrugTrials.org.cn: ChiCTR2100049732). The primary endpoint was safety and tolerability of E4F4. Secondary endpoints were pharmacokinetic, pharmacodynamic and immunogenicity profiles of E4F4. Safety data to day 15 after the final subject in a cohort had been dosed were reviewed before commencing the next dose level. RESULTS: E4F4 was safe and well tolerated among healthy Chinese participants in this study. There was no obvious dose-dependent relationship between frequency, severity or causality of treatment-emergent adverse events. Cmax and area under the curve of E4F4 were dose proportional over the 0.45-14.85 mg dose range. Median Tmax and t1/2 ranged from 146 to 210 h and 199 to 252 h, respectively, across E4F4 doses, with no dose-dependent trends. For the intravenous glucose tolerance test, area under the curve of glucose in plasma from time 0 to 180 min showed a dose-response relationship in the 1.8-10.35 mg dose range, with an increased response at the higher doses. CONCLUSION: E4F4 exhibited an acceptable safety profile and linear pharmacokinetics in healthy subjects. The recommended phase 2 dose is 4.5-10.35 mg once every 2 weeks.


Asunto(s)
Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Exenatida/efectos adversos , Voluntarios Sanos , Área Bajo la Curva , Prueba de Tolerancia a la Glucosa , Método Doble Ciego , Relación Dosis-Respuesta a Droga
12.
Inorg Chem ; 63(5): 2418-2430, 2024 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-38264973

RESUMEN

Uranyl cation, as an emerging photocatalyst, has been successfully applied to synthetic chemistry in recent years and displayed remarkable catalytic ability under visible light. However, the molecular-level reaction mechanisms of uranyl photocatalysis are unclear. Here, we explore the mechanism of the stepwise benzylic C-H oxygenation of typical alkyl-substituted aromatics (i.e., toluene, ethylbenzene, and cumene) via uranyl photocatalysis using theoretical and experimental methods. Theoretical calculation results show that the most favorable reaction path for uranyl photocatalytic oxidation is as follows: first, hydrogen atom transfer (HAT) from the benzyl position to form a carbon radical ([R•]), then oxygen addition ([R•] + O2 → [ROO•]), then radical-radical combination ([ROO•] + [R•] → [ROOR] → 2[RO•]), and eventually [RO•] reduction to produce alcohols, of which 2° alcohol would further be oxidized to ketones and 1° would be stepwise-oxygenated to acids. The results of the designed verification experiments and the capture of reactive intermediates were consistent with those of theoretical calculations and the previously reported research that the active benzylic C-H would be stepwise-oxygenated in the presence of uranyl. This work deepens our understanding of the HAT mechanism of uranyl photocatalysis and provides important theoretical support for the relevant application of uranyl photocatalysts in organic transformation.

13.
Org Biomol Chem ; 22(8): 1634-1638, 2024 02 21.
Artículo en Inglés | MEDLINE | ID: mdl-38323382

RESUMEN

Alzheimer's disease (AD) is characterized by cognitive decline, often attributed to the deficiency of acetylcholine, which can undergo hydrolysis by acetylcholinesterase (AChE) within the biological milieu. Here, we report a supramolecular strategy that takes advantage of confinement effects to inhibit such a hydrolysis process, shedding some light on AD therapy. A water-soluble and bowl-shaped molecule, hexacarboxylated tribenzotriquinacene (TBTQ-C6), was employed to shield acetylcholine (G1) from enzymatic degradation through host-guest binding interactions. Our study revealed highly efficient host-guest interactions with a binding ratio of 1 : 3, resulting in a significant reduction in acetylcholine hydrolysis from 91.1% to 7.4% in the presence of AChE under otherwise identical conditions. Furthermore, TBTQ-C6 showed potential for attenuating the degradation of butyrylcholine (G2) by butyrylcholinesterase (BChE). The broader implications of this study extend to the potential use of molecular containers in various biochemical and pharmacological applications, opening new avenues for research in the field of neurodegenerative diseases.


Asunto(s)
Enfermedad de Alzheimer , Butirilcolinesterasa , Humanos , Butirilcolinesterasa/metabolismo , Acetilcolina/metabolismo , Acetilcolina/uso terapéutico , Acetilcolinesterasa/metabolismo , Hidrólisis , Enfermedad de Alzheimer/tratamiento farmacológico , Inhibidores de la Colinesterasa/química , Simulación del Acoplamiento Molecular
14.
Toxicol Pathol ; 52(1): 35-54, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38385340

RESUMEN

Recombinant adeno-associated virus (AAV)-mediated degeneration of sensory neurons in the dorsal root ganglia (DRG) and trigeminal ganglia (TG) has been observed in non-human primates (NHPs) following intravenous (IV) and intrathecal (IT) delivery. Administration of recombinant AAV encoding a human protein transgene via a single intra-cisterna magna (ICM) injection in New Zealand white rabbits resulted in histopathology changes very similar to NHPs: mononuclear cell infiltration, degeneration/necrosis of sensory neurons, and nerve fiber degeneration of sensory tracts in the spinal cord and of multiple nerves. AAV-associated clinical signs and incidence/severity of histologic findings indicated that rabbits were equally or more sensitive than NHPs to sensory neuron damage. Another study using human and rabbit transgene constructs of the same protein demonstrated comparable changes suggesting that the effects are not an immune response to the non-self protein transgene. Rabbit has not been characterized as a species for general toxicity testing of AAV gene therapies, but these studies suggest that it may be an alternative model to investigate mechanisms of AAV-mediated neurotoxicity and test novel AAV designs mitigating these adverse effects.


Asunto(s)
Dependovirus , Ganglios Espinales , Animales , Conejos , Dependovirus/genética , Vectores Genéticos , Masculino , Humanos , Transgenes , Femenino , Células Receptoras Sensoriales
15.
Phys Chem Chem Phys ; 26(9): 7545-7553, 2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38357997

RESUMEN

The stability of actinide-mineral solid solution in a water environment is critical for assessing the safety of nuclear-waste geological repositories and studying actinide migration in natural systems. However, the dissolution behavior of actinide ions incorporated at the mineral-water interface is still unclear at the atomic level. Herein, we present metadynamics simulations of the reaction pathways, thermodynamics and kinetics of trivalent curium ions (Cm3+) dissolving from calcite surfaces. Cm3+ ions incorporated in different calcite surfaces (i.e., terrace and stepped surfaces) with distinct coordination environments have different reaction pathways, free energy barriers and free energy changes. We found that Cm dissolution from a stepped surface is more favorable than that from a terrace surface, both thermodynamically and kinetically. In addition, water molecules seem to promote the detachment of curium ions from the surface by exerting a pulling force via water coordination with Cm3+ and a pushing force via proton migration to the surface layer and water diffusion in the vacant Cm site. Thus, the findings from this work prove to be a milestone in revealing the dynamic dissolution mechanism of trivalent actinides from minerals and would also help predict the dissolution behaviors of other metal ions at the solid-water interface in chemical and environmental sciences.

16.
Phys Chem Chem Phys ; 26(3): 2242-2248, 2024 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-38165283

RESUMEN

Ferroelectric materials have attracted increasing attention due to their rich properties. Unlike perovskite ferroelectric oxides, in the LiNbO3-type ferroelectric oxides of ABO3, ferroelectrically active cations are not necessary. While the effects of carrier doping on perovskite ferroelectric oxides have been extensively studied, the studies on LiNbO3-type ferroelectric oxides are rare. We consider two LiNbO3-type ferroelectric oxides ZnSnO3 and ZnTiO3, where the former has no ferroelectrically active cation and the latter has ferroelectrically active cation Ti4+, and study the effect of carrier doping by performing first-principles calculations. Comparison results indicate that the B-site cation has significant effects on the polar distortion in LN-type ferroelectrics. Our studies show that LN-type materials can maintain the coexistence of ferroelectricity and conductance over a very wide range of concentrations. The polar displacement is even enhanced under hole doping. More importantly, ZnSnO3 can be doped by electrons up to a high level to realize the conducting ferroelectrics of high mobility due to its isolated s conduction band.

17.
Acta Pharmacol Sin ; 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38956416

RESUMEN

Abnormal accumulation of hyperphosphorylated tau protein plays a pivotal role in a collection of neurodegenerative diseases named tauopathies, including Alzheimer's disease (AD). We have recently conceptualized the design of hetero-bifunctional chimeras for selectively promoting the proximity between tau and phosphatase, thus specifically facilitating tau dephosphorylation and removal. Here, we sought to optimize the construction of tau dephosphorylating-targeting chimera (DEPTAC) and obtained a new chimera D14, which had high efficiency in reducing tau phosphorylation both in cell and tauopathy mouse models, while showing limited cytotoxicity. Moreover, D14 ameliorated neurodegeneration in primary cultured hippocampal neurons treated with toxic tau-K18 fragments, and improved cognitive functions of tauopathy mice. These results suggested D14 as a cost-effective drug candidate for the treatment of tauopathies.

18.
Support Care Cancer ; 32(4): 235, 2024 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-38502260

RESUMEN

OBJECTIVES: This review examined the effectiveness of using dance movement therapy (DMT) and dance movement interventions (DMIs) with cancer and palliative care patients. METHODS: A systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Six databases were searched from inception to July 9, 2022, without limits on year or age. Searching was updated on July 10, 2023. The risk of bias was assessed by the Cochrane (RoB 2) and ROBINS-I tools. Meta-analyses were conducted to pool estimates of the effects of DMT and DMI on patients' health-related outcomes. A narrative synthesis of outcomes was performed where meta-analysis was not appropriate. RESULTS: Among a total of 16 studies included in this review, nine were randomized controlled trials and seven were non-randomized trials, with a total of 893 participants. Only six of these studies were fully or partially described as true DMTs (some with less clarity than others), whereas the majority (n = 10) were DMIs with unclear therapeutic alignment. Most studies focused on female patients with breast cancer. Cancer patients undergoing palliative care received little attention. The overall risk of bias from the evaluated studies was high. Meta-analysis of two trials revealed that DMTs had no effect on QOL in cancer patients (SMD - 0.09, 95% CI - 0.21-0.40, P = 0.54), while narrative analysis and non-randomized trials showed no overall effect of DMTs on anxiety, depression, body image, self-esteem, or sleep disturbance but significant positive effects on perceived stress, pain severity, and pain interference. DMIs had significant positive effects on cancer patients' depression (SMD - 0.53, 95% CI - 0.93 to - 0.14, P = 0.008) and fatigue (SMD - 0.42, 95% CI - 0.70 to - 0.14, P = 0.003). DMI trials synthesized narratively showed an effect on patients' body image, self-esteem, physical function, right and left handgrip strength, life satisfaction, and the mental component of QOL. CONCLUSION: Both DMT and DMIs had promising effects on several health outcomes, but results were inconsistent, and the evidence was weak. The reviewed studies' low evidence quality and small sample sizes affected the findings' robustness and reliability. Large-scale, high-quality randomized controlled trials with sufficient sample sizes, and clear and veracious DMT and DMI protocols and data are required to provide more credible research evidence and influence practice.


Asunto(s)
Neoplasias de la Mama , Danzaterapia , Baile , Femenino , Humanos , Danzaterapia/métodos , Depresión/terapia , Fuerza de la Mano , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Reproducibilidad de los Resultados , Masculino
19.
Antonie Van Leeuwenhoek ; 117(1): 28, 2024 Jan 27.
Artículo en Inglés | MEDLINE | ID: mdl-38280034

RESUMEN

A novel Gram-stain-negative, strictly aerobic and bioflocculant-producing bacterium, designated as ASW11-36T, was isolated from an intertidal sand collected from coastal areas of Qingdao, PR China. Growth occurred at 15-40 °C (optimum, 30 °C), pH 7.0-9.0 (optimum, pH 7.5) and with 1.5-7.0% (w/v) NaCl (optimum, 2.5-3.0%). In the whole-cell fatty acid pattern prevailed C16:0 and summed feature 3 (C16:1 ω7c and/or C16:1 ω6c). The major isoprenoid quinone was determined to be Q-8 and the major polar lipids were phosphatidylethanolamine (PE) and phosphatidylglycerol (PG), one unidentified aminolipid (AL), one unidentified glycolipid (GL), and two lipids (L1, L2). Based on the phylogenetic analyses of 16S rRNA gene sequences and 618 single-copy orthologous clusters, strain ASW11-36T could represent a novel member of the genus Alteromonas and was closely related to Alteromonas flava P0211T (98.4%) and Alteromonas facilis P0213T (98.3%). The pairwise average nucleotide identity and digital DNA-DNA hybridization values of the ASW11-36T genome assembly against the closely related species genomes were 71.8% and 21.7%, respectively, that clearly lower than the proposed thresholds for species. Based on phenotypic, phylogenetic, and chemotaxonomic analyses, strain ASW11-36T is considered to represent a novel species of the genus Alteromonas, for which the name Alteromonas arenosi sp. nov. is proposed. The type strain is ASW11-36T (= KCTC 82496T = MCCC 1K05585T). In addition, the strain yielded 65% of flocculating efficiency in kaolin suspension with CaCl2 addition. The draft genome of ASW11-36T shared abundant putative CAZy family related genes, especially involved in the biosynthesis of exopolysaccharides, implying its potential environmental and biological applications.


Asunto(s)
Alteromonas , Arena , Filogenia , ARN Ribosómico 16S/genética , Técnicas de Tipificación Bacteriana , Ácidos Grasos , Ubiquinona , ADN , Análisis de Secuencia de ADN , ADN Bacteriano/genética , Fosfolípidos
20.
Langenbecks Arch Surg ; 409(1): 112, 2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38587671

RESUMEN

INTRODUCTION: Either extracorporeal anastomosis (EA) or intracorporeal anastomosis (IA) could be selected for digestive reconstruction in laparoscopic right hemicolectomy (LRH). However, whether LRH with IA is feasible and beneficial for overweight right-side colon cancer (RCC) is unclear. This study aims to investigate the feasibility and advantage of IA in LRH for overweight RCC. METHODS: Forty-eight consecutive overweight RCC patients undergoing LRH with IA were matched with 48 consecutive cases undergoing LRH with EA. Both clinical and surgical data were collected and analyzed. RESULTS: The incidence of postoperative complications was 20.8% (10/48) in the EA group and 14.6% (7/48) in the IA group respectively, with no statistical difference. Compared to the EA group, patients in the IA group revealed faster gas (40.2 + 7.8 h vs. 45.6 + 7.9 h, P = 0.001) and stool discharge (4.0 + 1.2 d vs. 4.5 + 1.1 d, P = 0.040), shorter assisted incision (5.3 + 1.3 cm vs. 7.5 + 1.2 cm, P = 0.000), and less analgesic used (3.3 + 1.3 d vs. 4.0 + 1.3 d, P = 0.012). There were no significant differences in operation time, blood loss, or postoperative hospital stays. In the IA group, the first one third of cases presented longer operation time (228.4 + 29.3 min) compared to the middle (191.0 + 35.0 min, P = 0.003) and the last one third of patients (182.2 + 20.7 min, P = 0.000). CONCLUSION: LRH with IA is feasible and safe for overweight RCC, with faster bowel function recovery and less pain. Accumulation of certain cases of LRH with IA will facilitate surgical procedures and reduce operation time.


Asunto(s)
Carcinoma de Células Renales , Neoplasias del Colon , Neoplasias Renales , Laparoscopía , Humanos , Estudios de Casos y Controles , Sobrepeso , Neoplasias del Colon/cirugía , Colectomía , Anastomosis Quirúrgica
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