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1.
Nature ; 621(7978): 312-317, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37532941

RESUMEN

The balance between degradation and preservation of sedimentary organic carbon (OC) is important for global carbon and oxygen cycles1. The relative importance of different mechanisms and environmental conditions contributing to marine sedimentary OC preservation, however, remains unclear2-8. Simple organic molecules can be geopolymerized into recalcitrant forms by means of the Maillard reaction5, although reaction kinetics at marine sedimentary temperatures are thought to be slow9,10. More recent work in terrestrial systems suggests that the reaction can be catalysed by manganese minerals11-13, but the potential for the promotion of geopolymerized OC formation at marine sedimentary temperatures is uncertain. Here we present incubation experiments and find that iron and manganese ions and minerals abiotically catalyse the Maillard reaction by up to two orders of magnitude at temperatures relevant to continental margins where most preservation occurs4. Furthermore, the chemical signature of the reaction products closely resembles dissolved and total OC found in continental margin sediments globally. With the aid of a pore-water model14, we estimate that iron- and manganese-catalysed transformation of simple organic molecules into complex macromolecules might generate on the order of approximately 4.1 Tg C yr-1 for preservation in marine sediments. In the context of perhaps only about 63 Tg C yr-1 variation in sedimentary organic preservation over the past 300 million years6, we propose that variable iron and manganese inputs to the ocean could exert a substantial but hitherto unexplored impact on global OC preservation over geological time.

2.
Proc Natl Acad Sci U S A ; 120(48): e2309378120, 2023 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-37983494

RESUMEN

The impact of a scientific publication is often measured by the number of citations it receives from the scientific community. However, citation count is susceptible to well-documented variations in citation practices across time and discipline, limiting our ability to compare different scientific achievements. Previous efforts to account for citation variations often rely on a priori discipline labels of papers, assuming that all papers in a discipline are identical in their subject matter. Here, we propose a network-based methodology to quantify the impact of an article by comparing it with locally comparable research, thereby eliminating the discipline label requirement. We show that the developed measure is not susceptible to discipline bias and follows a universal distribution for all articles published in different years, offering an unbiased indicator for impact across time and discipline. We then use the indicator to identify science-wide high impact research in the past half century and quantify its temporal production dynamics across disciplines, helping us identifying breakthroughs from diverse, smaller disciplines, such as geosciences, radiology, and optics, as opposed to citation-rich biomedical sciences. Our work provides insights into the evolution of science and paves a way for fair comparisons of the impact of diverse contributions across many fields.


Asunto(s)
Bibliometría , Factor de Impacto de la Revista , Sesgo , Logro
3.
Small ; 20(16): e2304318, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38018305

RESUMEN

The long-term inflammatory microenvironment is one of the main obstacles to inhibit acute spinal cord injury (SCI) repair. The natural adipose tissue-derived extracellular matrix hydrogel shows effective anti-inflammatory regulation because of its unique protein components. However, the rapid degradation rate and removal of functional proteins during the decellularization process impair the lasting anti-inflammation function of the adipose tissue-derived hydrogel. To address this problem, adipose tissue lysate provides an effective way for SCI repair due to its abundance of anti-inflammatory and nerve regeneration-related proteins. Thereby, human adipose tissue lysate-based hydrogel (HATLH) with an appropriate degradation rate is developed, which aims to in situ long-term recruit and induce anti-inflammatory M2 macrophages through sustainedly released proteins. HATLH can recruit and polarize M2 macrophages while inhibiting pro-inflammatory M1 macrophages regardless of human or mouse-originated. The axonal growth of neuronal cells also can be effectively improved by HATLH and HATLH-induced M2 macrophages. In vivo experiments reveal that HATLH promotes endogenous M2 macrophages infiltration in large numbers (3.5 × 105/100 µL hydrogel) and maintains a long duration for over a month. In a mouse SCI model, HATLH significantly inhibits local inflammatory response, improves neuron and oligodendrocyte differentiation, enhances axonal growth and remyelination, as well as accelerates neurological function restoration.


Asunto(s)
Hidrogeles , Traumatismos de la Médula Espinal , Humanos , Ratones , Animales , Hidrogeles/farmacología , Traumatismos de la Médula Espinal/tratamiento farmacológico , Neuronas/metabolismo , Macrófagos/metabolismo , Antiinflamatorios/uso terapéutico
4.
Chemistry ; 30(27): e202400296, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38427538

RESUMEN

Lipophilic biphenylthiophene- and phenanthrothiophene-triazine compounds, BPTTn and CPTTn, respectively, were prepared by a tandem procedure involving successive Suzuki-Miyaura coupling and Scholl cyclodehydrogenation reactions. These compounds display photoluminescence in solution and in thin film state, solvatochromism with increasing solvent's polarity, as well as acidochromism and metal ion recognition stimuli-responsive fluorescence. Protonation of BPTT10 and CPTT10 by trifluoroacetic acid results in fluorescence quenching, which is reversibly restored once treated with triethylamine (ON-OFF switch). DFT computational studies show that intramolecular charge transfer (ICT) phenomena occurs for both molecules, and reveal that protonation enhances the electron-withdrawing ability of the triazine core and reduces the band gap. This acidochromic behavior was applied to a prototype fluorescent anti-counterfeiting device. They also specifically recognize Fe3+ through coordination, and the recognition mechanism is closely related to the photoinduced electron transfer between Fe3+ and BPTT10/CPTT10. CPTTn self-assemble into columnar rectangular (Colrec) mesophase, which can be modulated by oleic acid via the formation of a hydrogen-bonded supramolecular liquid crystal hexagonal Colhex mesophase. Finally, CPTTn also form organic gels in alkanes at low critical gel concentration (3.0 mg/mL). Therefore, these star-shaped triazine molecules possess many interesting features and thus hold great promises for information processing, liquid crystal semiconductors and organogelators.

5.
Appl Opt ; 63(8): 1929-1933, 2024 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-38568630

RESUMEN

Nanocomposite scintillators are expected to combine the advantages of inorganic and plastic scintillators, such as high detection efficiency, high light yield, fast decay time, low cost, and ease of processing. They are currently the forefront and hot field of scintillator research. In this study, a non-destructive method was developed for measuring the content of inorganic components in nanocomposite scintillators by terahertz time-domain spectroscopy. The complex refractive index of B a F 2 nanocomposite scintillators with different mass contents was measured in the terahertz band. As the mass content of B a F 2 nanoparticles increases, the refractive index and extinction coefficient of B a F 2 nanocomposite scintillators also gradually increase in the terahertz band. By combining the effective medium theory, the expected mass content was obtained, proving the feasibility of this measuring method.

6.
Phys Rev Lett ; 130(21): 214001, 2023 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-37295099

RESUMEN

We present an experimental study of the velocity circulation in a quasi-two-dimensional turbulent flow. We show that the area rule of circulation around simple loops holds in both the forward cascade enstrophy inertial range (ΩIR) and the inverse cascade energy inertial range (EIR): When the side lengths of a loop are all within the same inertial range, the circulation statistics depend on the loop area alone. It is also found that, for circulation around figure-eight loops, the area rule still holds in EIR but is not applicable in ΩIR. In ΩIR, the circulation is nonintermittent; whereas in EIR, the circulation is bifractal: space filling for moments of the order of 3 and below and a monofractal with a dimension of 1.42 for higher orders. Our results demonstrate, as in a numerical study of 3D turbulence [K. P. Iyer et al., Circulation in High Reynolds Number Isotropic Turbulence is a Bifractal, Phys. Rev. X 9, 041006 (2019).PRXHAE2160-330810.1103/PhysRevX.9.041006], that, in terms of circulation, turbulent flows exhibit a simpler behavior than velocity increments, as the latter are multifractals.

7.
Chemistry ; 29(56): e202301829, 2023 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-37452614

RESUMEN

The straightforward synthesis of several Fluorinated Polycyclic Aromatic Hydrocarbons by the efficient, transition-metal-free, arene fluorine nucleophilic substitution reaction is described, and the full investigation of their liquid crystalline and optical properties reported. The key precursors for this study, i. e. 2,2'-dilithio-4,4',5,5'-tetraalkoxy-1,1'-biphenyl derivatives, were obtained in two steps from the highly selective Scholl oxidative homo-coupling of 3,4-dialkoxy-1-bromobenzene, followed by quantitative double-lithiation. In situ room temperature nucleophilic annulation with either perfluorobenzene or perfluoronaphthalene leads to 1,2,3,4-tetrafluoro-6,7,10,11-tetraalkxoytriphenylenes and 9,10,11,12,13,14-hexafluoro-2,3,6,7-tetraalkoxybenzo[f]tetraphenes, respectively, in good yields. Exploiting the same strategy, subsequent double annulations resulted in the formation of 9,18-difluoro-2,3,6,7,11,12,15,16-octa(alkoxy)tribenzo[f,k,m]tetraphenes and 9,10,19,20-tetrafluoro-2,3,6,7,12,13,16,17-octakis(hexyloxy)tetrabenzo[a,c,j,l]tetracenes, respectively. Despite the presence of only four alkoxy chains, the polar "Janus" mesogens display a columnar hexagonal mesophase over broad temperature ranges, with higher mesophase stability than the archetypical 2,3,6,7,10,11-hexa(alkoxy)triphenylenes and their hydrogenated counterparts. The improvement or induction of mesomorphism is attributed to efficient antiparallel face-to-face π-stacking driven by the establishment of non-covalent perfluoroarene-arene intermolecular interactions. The larger lipophilic discotic π-extended compounds also exhibit columnar mesomorphism, over similar temperature ranges and stability than their hydrogenated homologs. Finally, these fluorinated molecules form stringy gels in various solvents, and show interesting solvatochromic emission properties in solution as well as strong emission in thin films and gels.

8.
Nanotechnology ; 35(3)2023 Nov 03.
Artículo en Inglés | MEDLINE | ID: mdl-37725953

RESUMEN

After investigating the behavior of ions during the growth of conductive filaments, we suggested a model for the growth process and electrical characteristics of the conductive filament under current-driven mode. In this model, the ionic displacement equation is derived by Arrhenius law, and a differential equation for the conductive filament growth has been established. We have also proved that the dielectric layer with the leakage current under current-driven mode can be equivalent to a parallel plate capacitor, which has a the equivalent dielectric constant. Consequently, the forming/set time of the device is gotten. At the same time, the kinetics process of ion motion is analyzed in detail, so that many microscopic parameters of the ion motion, such as the height of the potential barrier, the jump step, mobility and diffusion coefficient, can be obtained. Due to divalent and monovalent copper ions all participate in conduction, an equivalent copper ion Cuz+is used for replacing both Cu+and Cu2+, solving the computational complexity problem caused by multivalent metal ions. Finally, an equivalent circuit is proposed to calculate output voltage versus time characteristic. The calculation results of the model are consistent with experimental data.

9.
Environ Sci Technol ; 57(45): 17501-17510, 2023 11 14.
Artículo en Inglés | MEDLINE | ID: mdl-37921659

RESUMEN

The mobility of chromium (Cr) is controlled by minerals, especially iron (oxyhydr)oxides. The influence of organic carbon (OC) on the mobility and fate of Cr(VI) during Fe(II)-induced transformation of iron (oxyhydr)oxide, however, is still unclear. We investigate how low-weight carboxyl-rich OC influences the transformation of ferrihydrite (Fh) and controls the mobility of Cr(VI/III) in reducing environments and how Cr influences the formation of secondary Fe minerals and the stabilization of OC. With respect to the transformation of Fe minerals, the presence of low-weight carboxyl-rich OC retards the growth of goethite crystals and stabilizes lepidocrocite for a longer time. With respect to the mobility of Cr, low-weight carboxyl-rich OC suppresses the Cr(III)non-extractable associated with Fe minerals, and this suppression is enhanced with increasing carboxyl-richness of OC and decreasing pH. The presence of Cr(III) mitigates the decrease in total C associated with Fe minerals and increases the Cnon-extractable especially for Fh organominerals made with carboxyl-rich OC. Our study sheds new light on the mobility and fate of Cr in reducing environments and suggests that there is a potential synergy between Cr(VI) remediation and OC stabilization.


Asunto(s)
Carbono , Minerales , Oxidación-Reducción , Minerales/química , Compuestos Férricos/química , Cromo/química , Hierro/química , Óxidos , Compuestos Ferrosos
10.
BMC Geriatr ; 23(1): 142, 2023 03 14.
Artículo en Inglés | MEDLINE | ID: mdl-36918794

RESUMEN

BACKGROUND: Rapidly progressive dementia (RPD) is a syndrome originating from various diseases. Recent advances have allowed a better understanding of its categories and spectrum; however, it remains challenging to make an accurate differential diagnosis and prognosis prediction. METHODS: This study was a retrospective evaluation of all participants admitted to the neurology department of a single center in China from January 2015 to December 2019. The screened patients met the RPD criteria and their characteristics were collected to explore a diagnostic pattern of RPD. In addition, outcomes of RPD were evaluated with the Glasgow Outcome Scale (GOS), activities of daily living scale (ADL), and simplified Mini-Mental State Examination (MMSE), and different prognostic analysis methods were performed to determine the prognostic factors of RPD. RESULTS: A total of 149 RPD patients among 15,731 inpatients were identified with an average MMSE value of 13.0 ± 4.6 at baseline. Etiological epidemiology revealed infectious, neurodegenerative and toxic/metabolic diseases as the three largest groups, accounting for 26.2%, 20.8% and 16.8% of all cases, respectively. In particular, prevalence rates of Creutzfeldt-Jakob disease (13.4%), Alzheimer's disease (11.4%), carbon monoxide poisoning (8.1%), neurosyphilis (5.4%) and dementia with Lewy bodies (5.4%) were highest in this series. A recommended diagnostic framework for RPD etiology was thus established. Follow-up evaluations showed a negative correlation between age and GOS scores (r=-0.421, P < 0.001), as well as age and simplified MMSE scores (rs =- 0.393, P < 0.001), and a positive correlation between age and ADL scores (rs =0.503, P < 0.001), and significantly different GOS, ADL and simplified MMSE scores across various etiologies (P = 0.003; F = 9.463, P < 0.001; F = 6.117, P < 0.001). CONCLUSION: Infectious, neurodegenerative and toxic-metabolic entities were the most common RPD categories, and establishing a practical approach to RPD etiology would allow better disease management.


Asunto(s)
Enfermedad de Alzheimer , Síndrome de Creutzfeldt-Jakob , Humanos , Estudios Retrospectivos , Prevalencia , Actividades Cotidianas , Progresión de la Enfermedad , Síndrome de Creutzfeldt-Jakob/diagnóstico , Enfermedad de Alzheimer/diagnóstico
11.
Molecules ; 28(4)2023 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-36838709

RESUMEN

π-Extended pyrene compounds possess remarkable luminescent and semiconducting properties and are being intensively investigated as electroluminescent materials for potential uses in organic light-emitting diodes, transistors, and solar cells. Here, the synthesis of two sets of pyrene-containing π-conjugated polyaromatic regioisomers, namely 2,3,10,11,14,15,20,21-octaalkyloxypentabenzo[a,c,m,o,rst]pentaphene (BBPn) and 2,3,6,7,13,14,17,18-octaalkyloxydibenzo[j,tuv]phenanthro [9,10-b]picene (DBPn), is reported. They were obtained using the Suzuki-Miyaura cross-coupling in tandem with Scholl oxidative cyclodehydrogenation reactions from the easily accessible precursors 1,8- and 1,6-dibromopyrene, respectively. Both sets of compounds, equipped with eight peripheral aliphatic chains, self-assemble into a single hexagonal columnar mesophase, with one short-chain BBPn homolog also exhibiting another columnar mesophase at a lower temperature, with a rectangular symmetry; BBPn isomers also possess wider mesophase ranges and higher mesophases' stability than their DBPn homologs. These polycyclic aromatic hydrocarbons all show a strong tendency of face-on orientation on the substrate and could be controlled to edge-on alignment through mechanical shearing of interest for their implementation in photoelectronic devices. In addition, both series BBPn and DBPn display green-yellow luminescence, with high fluorescence quantum yields, around 30%. In particular, BBPn exhibit a blue shift phenomenon in both absorption and emission with respect to their DBPn isomers. DFT results were in good agreement with the optical properties and with the stability ranges of the mesophases by confirming the higher divergence from the flatness of DBPn compared with BBPn. Based on these interesting properties, these isomers could be potentially applied not only in the field of fluorescent dyes but also in the field of organic photoelectric semiconductor materials as electron transport materials.


Asunto(s)
Hidrocarburos Policíclicos Aromáticos , Pirenos , Transporte de Electrón , Fluorescencia , Poli A
12.
Environ Microbiol ; 24(2): 752-761, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-33769668

RESUMEN

Arsenic can be biomethylated to form a variety of organic arsenicals differing in toxicity and environmental mobility. Trivalent methylarsenite (MAs(III)) produced in the methylation process is more toxic than inorganic arsenite (As(III)). MAs(III) also serves as a primitive antibiotic and, consequently, some environmental microorganisms have evolved mechanisms to detoxify MAs(III). However, the mechanisms of MAs(III) detoxification are not well understood. In this study, we identified an arsenic resistance (ars) operon consisting of three genes, arsRVK, that contribute to MAs(III) resistance in Ensifer adhaerens ST2. ArsV is annotated as an NADPH-dependent flavin monooxygenase with unknown function. Expression of arsV in the arsenic hypersensitive Escherichia coli strain AW3110Δars conferred resistance to MAs(III) and the ability to oxidize MAs(III) to MAs(V). In the presence of NADPH and either FAD or FMN, purified ArsV protein was able to oxidize both MAs(III) to MAs(V) and Sb(III) to Sb(V). Genes with arsV-like sequences are widely present in soils and environmental bacteria. Metagenomic analysis of five paddy soils showed the abundance of arsV-like sequences of 0.12-0.25 ppm. These results demonstrate that ArsV is a novel enzyme for the detoxification of MAs(III) and Sb(III) and the genes encoding ArsV are widely present in soil bacteria.


Asunto(s)
Arsénico , Arsenicales , Antimonio , Arsenicales/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Flavinas , Oxigenasas de Función Mixta , Suelo
13.
Sensors (Basel) ; 22(19)2022 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-36236702

RESUMEN

As protection for nuclear power plants is quite necessary, the nuclear fuel is sealed in zirconium alloy thin wall cladding. During service, fuel rods might be damaged caused by wall-thickness thinning, cladding corrosion and cracking, etc. This will cause the coolant to enter into the fuel rod, which may lead to the failure of the fuel assembly. However, current diagnostic methods have limitations due to the special structure of the fuel assembly and the underwater and radioactive environment. In this paper, a novel inspection method is proposed to recognize the failure of a fuel rod. The fuel rod failure can be detected based on the presence or absence of coolant inside the fuel rod by using an ultrasonic plate wave. The inspection model and process algorithm are proposed for in-service inspection. The relationship between signal and scanning position is established and analyzed. Both ultrasound field simulation and experiment have been carried out for validation. The corresponding results illustrate that the failed nuclear fuel rod of the whole fuel assembly (including the internal rods) can be effectively detected without the influence of the near-field region by using the proposed method.

14.
Environ Microbiol ; 23(2): 924-933, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-32827180

RESUMEN

Autotrophic carbon dioxide (CO2 ) fixation by microbes is ubiquitous in the environment and potentially contributes to the soil organic carbon (SOC) pool. However, the multiple autotrophic pathways of microbial carbon assimilation and fixation in paddy soils remain poorly characterized. In this study, we combine metagenomic analysis with 14 C-labelling to investigate all known autotrophic pathways and CO2 assimilation mechanisms in five typical paddy soils from southern China. Marker genes of six autotrophic pathways are detected in all soil samples, which are dominated by the cbbL genes (67%-82%) coding the ribulose-bisphosphate carboxylase large chain in the Calvin cycle. These marker genes are associated with a broad range of phototrophic and chemotrophic genera. Significant amounts of 14 C-CO2 are assimilated into SOC (74.3-175.8 mg 14 C kg-1 ) and microbial biomass (5.2-24.1 mg 14 C kg-1 ) after 45 days incubation, where more than 70% of 14 C-SOC was concentrated in the relatively stable humin fractions. These results show that paddy soil microbes contain the genetic potential for autotrophic carbon fixation spreading over broad taxonomic ranges, and can incorporate atmospheric carbon into organic components, which ultimately contribute to the stable SOC pool.


Asunto(s)
Bacterias/genética , Bacterias/metabolismo , Dióxido de Carbono/metabolismo , Isótopos de Carbono/análisis , Microbiología del Suelo , Procesos Autotróficos , Bacterias/química , Bacterias/clasificación , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Ciclo del Carbono , Isótopos de Carbono/metabolismo , China , Marcaje Isotópico , Metagenoma , Metagenómica , Fotosíntesis , Ribulosa-Bifosfato Carboxilasa/genética , Ribulosa-Bifosfato Carboxilasa/metabolismo , Suelo/química
15.
Phys Rev Lett ; 127(24): 244501, 2021 Dec 10.
Artículo en Inglés | MEDLINE | ID: mdl-34951813

RESUMEN

An important and unresolved issue in rotating thermal turbulence is when the flow starts to feel the centrifugal effect. This onset problem is studied here by a novel experiment in which the centrifugal force can be varied over a wide range at fixed Rossby numbers by offsetting the apparatus from the rotation axis. Our experiment clearly shows that the centrifugal force starts to separate the hot and cold fluids at the onset Froude number 0.04. Additionally, this flow bifurcation leads to an unexpected heat transport enhancement and the existence of an optimal state. Based on the dynamical balance and characteristics of local flow structures, both the onset and optimal states are quantitatively explained.

16.
Neurol Sci ; 42(11): 4623-4628, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-33661484

RESUMEN

The pathogenesis of primary paroxysmal kinesigenic dyskinesia (PKD) remains unclear, and channelopathy is a possibility. In a pilot study, we found that PKD patients had abnormal exercise test (ET) results. To investigate the ET performances in patients affected by PKD, and the role of the channelopathies in the pathogenesis of PKD, we compared the ET results of PKD patients, control subjects, and hypokalemic periodic paralysis (HoPP) patients, and we analyzed ET changes in 32 PKD patients before and after treatment. Forty-four PKD patients underwent genetic testing for the PRRT2, SCN4A, and CLCN1 genes. Sixteen of 59 (27%) patients had abnormal ET results in the PKD group, while 28 of 35 (80%) patients had abnormal ET results in the HoPP group. Compared with the control group, the PKD group showed a significant decrease in the compound muscle action potential (CMAP) amplitude and area after the long ET (LET), while the HoPP group showed not only greater decreases in the CMAP amplitude and area after the LET but also greater increases in the CMAP amplitude and area immediately after the LET. The ET parameters before and after treatment were not significantly different. Nine of 44 PKD patients carried PRRT2 mutations, but the gene abnormalities were unrelated to any ET parameter. The PKD group demonstrated an abnormal LET result by electromyography (EMG), and this abnormality did not seem to correlate with the PRRT2 variant or sodium channel blocker therapy.


Asunto(s)
Prueba de Esfuerzo , Proteínas del Tejido Nervioso , Distonía , Humanos , Proteínas de la Membrana/genética , Mutación/genética , Canal de Sodio Activado por Voltaje NAV1.4 , Proteínas del Tejido Nervioso/genética , Proyectos Piloto
17.
Angew Chem Int Ed Engl ; 60(35): 19079-19084, 2021 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-34187100

RESUMEN

Controlling the chemo- and regioselectivity of transition-metal-catalyzed C-C activation remains a great challenge. The transformations of benzocyclobutenones (BCBs) usually involve the cleavage of C1-C2 bond. In this work, an unprecedented highly selective cleavage of C1-C8 bond with the insertion of alkynes is achieved by using blocking strategy via Ni catalysis, providing an efficient method for synthesis of 1,8-disubstituted naphthalenes. Notably, the blocking group could be readily removed after the transformation.

18.
J Neuroinflammation ; 17(1): 202, 2020 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-32631435

RESUMEN

BACKGROUND: Spinal cord injury (SCI) triggers the primary mechanical injury and secondary inflammation-mediated injury. Neuroinflammation-mediated insult causes secondary and extensive neurological damage after SCI. Microglia play a pivotal role in the initiation and progression of post-SCI neuroinflammation. METHODS: To elucidate the significance of LRCH1 to microglial functions, we applied lentivirus-induced LRCH1 knockdown in primary microglia culture and tested the role of LRCH1 in microglia-mediated inflammatory reaction both in vitro and in a rat SCI model. RESULTS: We found that LRCH1 was downregulated in microglia after traumatic SCI. LRCH1 knockdown increased the production of pro-inflammatory cytokines such as IL-1ß, TNF-α, and IL-6 after in vitro priming with lipopolysaccharide and adenosine triphosphate. Furthermore, LRCH1 knockdown promoted the priming-induced microglial polarization towards the pro-inflammatory inducible nitric oxide synthase (iNOS)-expressing microglia. LRCH1 knockdown also enhanced microglia-mediated N27 neuron death after priming. Further analysis revealed that LRCH1 knockdown increased priming-induced activation of p38 mitogen-activated protein kinase (MAPK) and Erk1/2 signaling, which are crucial to the inflammatory response of microglia. When LRCH1-knockdown microglia were adoptively injected into rat spinal cords, they enhanced post-SCI production of pro-inflammatory cytokines, increased SCI-induced recruitment of leukocytes, aggravated SCI-induced tissue damage and neuronal death, and worsened the locomotor function. CONCLUSION: Our study reveals for the first time that LRCH1 serves as a negative regulator of microglia-mediated neuroinflammation after SCI and provides clues for developing novel therapeutic approaches against SCI.


Asunto(s)
Mediadores de Inflamación/metabolismo , Proteínas de Microfilamentos/antagonistas & inhibidores , Proteínas de Microfilamentos/metabolismo , Microglía/metabolismo , Traumatismos de la Médula Espinal/metabolismo , Animales , Células Cultivadas , Inflamación/inducido químicamente , Inflamación/metabolismo , Inflamación/patología , Lipopolisacáridos/toxicidad , Masculino , Microglía/efectos de los fármacos , Microglía/patología , Ratas , Ratas Sprague-Dawley , Traumatismos de la Médula Espinal/patología
19.
J Recept Signal Transduct Res ; 40(6): 541-549, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32515250

RESUMEN

Context: Curcumin has shown efficacy in promoting radiosensitivity combined with radiotherapy. However, the role and mechanism of curcumin on radiosensitivity in laryngeal squamous cell cancer (LSCC) is largely unknown.Objective: The aim of our study is to explore the role of IKKγ-NF-κB signaling in curcumin enhancing LSCC cell radiosensitivity in vitro.Materials and methods: Curcumin and X-ray were used to induce cell DNA damage and apoptosis, or inhibit cell clone formation. IKKγ siRNA and plasmid were used to change IKKγ expression. The CCK8 assay was used to detect cell viability. Clone formation ability was analyzed using a clonogenic assay, cell apoptosis was examined using flow cytometry, an immunofluorescence assay was used to detect DNA damage, while mRNA and protein levels were assayed using real time PCR and western blotting, respectively.Results: Curcumin significantly enhanced irradiation-induced DNA damage and apoptosis, while weakening clone-forming abilities of LSCC cell line Hep2 and Hep2-max. Compared to Hep2 cells, Hep2-max cells are more sensitive to curcumin post-irradiation. Curcumin suppressed irradiation-induced NF-κB activation by suppressing IKKγ expression, but not IKKα and IKKß. Overexpression of IKKγ decreased irradiation-induced DNA damage and apoptosis, while promoting clone-forming abilities of Hep2 and Hep2-max cells. IKKγ overexpression further increased expression of NF-κB downstream genes, Bcl-XL, Bcl-2, and cyclin D1. Conversely, IKKγ silencing enhanced irradiation-induced DNA damage and apoptosis, but promoted clone formation in Hep2 and Hep2-max cells. Additionally, IKKγ silencing inhibited expression of Bcl-XL, Bcl-2, and cyclin D1.Conclusions: Curcumin enhances LSCC radiosensitivity via NF-ΚB inhibition by suppressing IKKγ expression.


Asunto(s)
Carcinoma de Células Escamosas/radioterapia , Curcumina/farmacología , Quinasa I-kappa B/antagonistas & inhibidores , Neoplasias Laríngeas/radioterapia , FN-kappa B/antagonistas & inhibidores , Tolerancia a Radiación/efectos de los fármacos , Fármacos Sensibilizantes a Radiaciones/farmacología , Antineoplásicos/farmacología , Apoptosis , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Laríngeas/tratamiento farmacológico , Neoplasias Laríngeas/metabolismo , Neoplasias Laríngeas/patología , Fosforilación , Transducción de Señal , Células Tumorales Cultivadas
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