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Stereotaxic injection of a specific brain region constitutes a fundamental experimental technique in basic neuroscience. Researchers commonly base their choice of stereotaxic injection parameters on mouse brain atlases or published materials that employed various populations/ages of mice and different stereotaxic equipment, necessitating further validation of the stereotaxic coordinate parameters. The efficacy of calcium imaging, chemogenetic, and optogenetic manipulations relies on the precise expression of reporter genes within the region of interest, often requiring several weeks of effort. Thus, it is a time-consuming task if the coordinates of the target brain region are not verified in advance. Using an appropriate dye instead of a virus and implementing cryosectioning, researchers can observe the injection site immediately following dye administration. This facilitates timely adjustments to coordinate parameters in cases where discrepancies exist between the actual injection site and the theoretical position. Such adjustments significantly enhance the accuracy of viral expression within the target region in subsequent experiments.
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Técnicas Estereotáxicas , Animales , Ratones , Crioultramicrotomía/métodos , Encéfalo/metabolismoRESUMEN
BACKGROUND: Time-restricted eating (TRE), a popular form of intermittent fasting, has shown benefits for improving metabolic diseases and cardiometabolic health. However, the effect of TRE in the regulation of blood pressure in primary hypertension remains unclear. METHODS: A 6-week randomized controlled trial was conducted, in which a total of 74 stage 1 primary hypertensive patients without high-risk were randomly assigned to Dietary Approaches to Stop Hypertension (DASH) group (n = 37) or DASH + TRE group (n = 37). Participants in the DASH + TRE group were instructed to consume their food within an 8-h window. Scientific research platform in We Chat application was used to track participants. The primary outcome was blood pressure. The secondary outcomes included body composition, cardiometabolic risk factors, inflammation-related parameters, urinary Na+ excretion, other clinical variables and safety outcomes. RESULTS: The reduction of systolic blood pressure and diastolic blood pressure were 5.595 ± 4.072 and 5.351 ± 5.643 mm Hg in the DASH group and 8.459 ± 4.260 and 9.459 ± 4.375 mm Hg in the DASH + TRE group. DASH + TRE group improved blood pressure diurnal rhythm. Subjects in DASH + TRE group had decreased extracellular water and increased urinary Na+ excretion. Furthermore, the decrease in blood pressure was associated with a reduction of extracellular water or increase in urinary Na+ excretion. In addition, safety outcomes such as nighttime hunger were also reported. CONCLUSION: Our study demonstrated that 8-h TRE + DASH diet caused a greater decrease in blood pressure in stage 1 primary hypertensive patients than DASH diet. This study may provide novel insights into the benefits of lifestyle modification in the treatment of primary hypertension. TRIAL REGISTRATION: https://www.chictr.org.cn/ (ChiCTR2300069393, registered on March 15, 2023).
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Presión Sanguínea , Enfoques Dietéticos para Detener la Hipertensión , Hipertensión , Humanos , Femenino , Masculino , Enfoques Dietéticos para Detener la Hipertensión/métodos , Persona de Mediana Edad , Hipertensión/dietoterapia , Hipertensión/terapia , Ayuno , Adulto , Resultado del TratamientoRESUMEN
Compensating for the intrinsic attosecond chirp (atto-chirp) of wideband high-order harmonics in the water window region is a significant challenge, in order to obtain isolated attosecond pulses (IAPs) with a width of tens of attoseconds (as). Here, we propose to realize the generation of IAP with duration as short as 20 as, central energy of 365 eV, and bandwidth exceeding 150 eV from chirp-free high harmonics generated by a four-color driving laser, without the necessity for atto-chirp compensation with natural materials. Unlike any other gating methods that an IAP arises from only one electron ionization event, we take advantage of the interference between harmonic radiation produced by multiple ionizing events. We further demonstrate that such chirp-free short IAP survives after taking account of macroscopic propagation effects. Given that the synthesized multicolor laser field can also effectively increase the harmonic flux, this work provides a practical way for experiments to generate the broad bandwidth chirp-free IAPs in the water window region.
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BACKGROUND: Thrombospondins (TSPs) play important roles in several cardiovascular diseases. However, the association between circulating (plasma) thrombospondin 2 (TSP2) and essential hypertension remains unclear. The present study was aimed to investigate the association of circulating TSP2 with blood pressure and nocturnal urine Na+ excretion and evaluate the predictive value of circulating TSP2 in subjects with hypertension. METHODS AND RESULTS: 603 newly diagnosed essential hypertensive subjects and 508 healthy subjects were preliminarily screened, 47 healthy subjects and 40 newly diagnosed essential hypertensive subjects without any chronic diseases were recruited. The results showed that the levels of circulating TSP2 were elevated in essential hypertensive subjects. The levels of TSP2 positively associated with systolic blood pressure (SBP), diastolic blood pressure (DBP), and other clinical parameters, including homeostasis model assessment of insulin resistance (HOMA-IR), brachial-ankle pulse wave velocity, and serum triglycerides, but negatively associated with nocturnal urine Na+ concentration and excretion and high-density lipoprotein cholesterol. Results of multiple linear regressions showed that HOMA-IR and nocturnal Na+ excretion were independent factors related to circulating TSP2. Mantel-Haenszel chi-square test displayed linear relationships between TSP2 and SBP (χ2 = 35.737) and DBP (χ2 = 26.652). The area under receiver operating characteristic curve (AUROC) of hypertension prediction was 0.901. CONCLUSION: Our study suggests for the first time that the circulating levels of TSP2 may be a novel potential biomarker for essential hypertension. The association between TSP2 and blood pressure may be, at least in part, related to the regulation of renal Na+ excretion, insulin resistance, and/or endothelial function.
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Hipertensión , Resistencia a la Insulina , Humanos , Índice Tobillo Braquial , Análisis de la Onda del Pulso , Trombospondinas , Sodio , Presión Sanguínea , Hipertensión Esencial/complicaciones , BiomarcadoresRESUMEN
Introduction: Bipolar disorder (BD) is a prevalent and disabling mental disorder characterized by disrupted circadian rhythms and impaired neurocognitive features, both of which fall under the major domains of Research Domain Criteria (RDoC). However, there is limited evidence regarding the interaction between circadian rhythms and long-term neurocognitive functioning. Therefore, this longitudinal cohort study protocol aims to explore whether circadian rhythm can predict changes in neurocognitive functioning over time in patients with BD.Methods: This study adopts a longitudinal cohort design, aiming to recruit 100 BD patients in either depressive or remitted states. Participants will undergo evaluations from clinical, circadian rhythm, and neurocognitive perspectives at baseline, 6-month, and 12-month follow-ups, involving questionnaires, actigraphy, and computed neurocognitive tests. We will examine both cross-sectional and longitudinal associations between participants' circadian rhythm patterns and neurocognitive functioning. Statistical analyses will employ Spearman correlation and mixed regression models.Discussion: We anticipate that circadian rhythms may serve as predictors of neurocognitive functioning changes. The findings of this study could offer supplementary insights into BD pathophysiology, potential treatment targets, and prediction.Trial Registration: This study has been registered with the Chinese Clinical Trial Registry under the registration code ChiCTR2200064922 on 21st October 2022.
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Trastorno Bipolar , Humanos , Trastorno Bipolar/complicaciones , Estudios Longitudinales , Estudios Transversales , Ritmo Circadiano/fisiología , Estudios de CohortesRESUMEN
Epidemiological studies show an association between low body selenium and the risk of hypertension. However, whether selenium deficiency causes hypertension remains unknown. Here, we report that Sprague-Dawley rats fed a selenium-deficient diet for 16 weeks developed hypertension, accompanied with decreased sodium excretion. The hypertension of selenium-deficient rats was associated with increased renal angiotensin II type 1 receptor (AT1R) expression and function that was reflected by the increase in sodium excretion after the intrarenal infusion of the AT1R antagonist candesartan. Selenium-deficient rats had increased systemic and renal oxidative stress; treatment with the antioxidant tempol for 4 weeks decreased the elevated blood pressure, increased sodium excretion, and normalized renal AT1R expression. Among the altered selenoproteins in selenium-deficient rats, the decrease in renal glutathione peroxidase 1 (GPx1) expression was most prominent. GPx1, via regulation of NF-κB p65 expression and activity, was involved in the regulation of renal AT1R expression because treatment with dithiocarbamate (PDTC), an NF-κB inhibitor, reversed the up-regulation of AT1R expression in selenium-deficient renal proximal tubule (RPT) cells. The up-regulation of AT1R expression with GPx1 silencing was restored by PDTC. Moreover, treatment with ebselen, a GPX1 mimic, reduced the increased renal AT1R expression, Na+-K+-ATPase activity, hydrogen peroxide (H2O2) generation, and the nuclear translocation of NF-κB p65 protein in selenium-deficient RPT cells. Our results demonstrated that long-term selenium deficiency causes hypertension, which is due, at least in part, to decreased urine sodium excretion. Selenium deficiency increases H2O2 production by reducing GPx1 expression, which enhances NF-κB activity, increases renal AT1R expression, causes sodium retention and consequently increases blood pressure.
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Hipertensión , Selenio , Animales , Ratas , Peróxido de Hidrógeno , Hipertensión/metabolismo , FN-kappa B/genética , FN-kappa B/metabolismo , Ratas Sprague-Dawley , Receptor de Angiotensina Tipo 1/genética , Selenio/deficiencia , SodioRESUMEN
Terahertz (THz) radiations from graphene are expected to provide a powerful light source for their wide applications. However, their conversion efficiencies are limited with either long-duration or few-cycle single-color laser pulses. Here, we theoretically demonstrate that THz waves can be efficiently generated from monolayer graphene by using a long-duration two-color laser pulse at normal incidence. Our simulated results show that low-frequency THz emissions are sensitive to the phase difference between two colors, the laser intensity, and the fundamental wavelength. Their dependence on these parameters can be very well reproduced by asymmetry parameters accounting for electron populations of conduction and valence bands. On the contrary, a newly defined σ parameter including the Landau-Zener tunneling probability cannot precisely predict such dependence. Furthermore, the waveform of THz electric field driven by two-color laser pulses exhibits the typical feature of a half-cycle pulse.
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The two-color strong-field mixing in gas medium is a widely used approach to generate bright broadband terahertz (THz) radiation. Here, we present a new, to the best of our knowledge, and counterintuitive method to promote THz performance in the two-color scheme. Beyond our knowledge that the maximum THz generation occurs with two-color foci overlapped, we found that, when the foci of two-color beams are noticeably separated along the propagation axis resulting in cascading plasmas, the THz conversion efficiency is surged by one order of magnitude and the bandwidth is stretched by more than two times, achieving 10-3 conversion efficiency and >100 THz bandwidth under the condition of 800/400 nm, â¼35 fs driving lasers. With the help of the pulse propagation equation and photocurrent model, the observations can be partially understood by the compromise between THz generation and absorption due to the spatial redistribution of laser energy in cascading plasmas. The present method can be extended to a mid-infrared driving laser, and new records of THz peak power and conversion efficiency are expected.
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Aflatoxin B1 (AFB1), which widely exists in soil and crops, is the most toxic aflatoxin and a carcinogen to humans and animals. The liver is the main organ that processes AFB1 and other mycotoxins and is also the main target of AFB1 toxicity. Taurine is known to exhibit a variety of physiological and pharmacological functions. In the present study, taurine was administered to detect the protective effect and mechanism of taurine in AFB1-induced liver injury in rats. The results showed that taurine inhibited the increase in hepatic injury indices, hepatic apoptosis and hepatic malondialdehyde (MDA) contents while significantly enhanced the hepatic activities of antioxidant enzymes and mitochondrial function-related indices in AFB1-poisoned rats. Meanwhile, the expression levels of key factors in the Nrf2 signalling pathway were upregulated while the expression levels of key proteins in the mitochondria-mediated apoptotic pathway were downregulated after taurine administration. The results showed that taurine can reverse AFB1-induced liver injury and abnormal apoptosis through activation of the Nrf2 signalling pathway and its downstream antioxidant enzymes, which further protects mitochondria from oxidative stress and the subsequent apoptotic pathway.
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Aflatoxina B1 , Enfermedad Hepática Crónica Inducida por Sustancias y Drogas , Aflatoxina B1/metabolismo , Aflatoxina B1/toxicidad , Animales , Antioxidantes/metabolismo , Antioxidantes/farmacología , Apoptosis , Enfermedad Hepática Crónica Inducida por Sustancias y Drogas/metabolismo , Hígado , Mitocondrias/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo , Ratas , Taurina/metabolismo , Taurina/farmacología , Taurina/uso terapéuticoRESUMEN
Botrytis cinerea is considered an important plant pathogen and is responsible for significant crop yield losses. With the frequent application of commercial fungicides, B. cinerea has developed resistance to many frequently used fungicides. Therefore, it is necessary to develop new kinds of fungicides with high activity and new modes of action to solve the increasingly serious problem of resistance. During our screening of fungicide candidates, one novel sulfonamide compound, N-(2-trifluoromethyl-4-chlorphenyl)-2-oxocyclohexyl sulfonamide (L13), has been found to exhibit good fungicidal activity against B. cinerea. In this work, the mode of action of L13 against B. cinerea and the field control effect on tomato gray mold was studied. L13 had good control against B. cinerea resistant to carbendazim, diethofencarb, and iprodione commercial fungicides in the pot culture experiments. SEM and TEM observations revealed that L13 could cause obvious morphological and cytological changes to B. cinerea, including excessive branching, irregular ramification or abnormal configuration, and the decomposition of cell wall and vacuole. L13 induced more significant electrolyte leakage from hyphae than procymidone as a positive control. L13 had only a minor effect on the oxygen consumption of intact mycelia, with 2.15% inhibition at 50 µg/mL. In two locations over 2 years, the field control effect of L13 against tomato gray mold reached 83% at a rate of 450 g ai ha-1, better than the commercial fungicide of iprodione. Moreover, toxicological tests demonstrated the low toxicological effect of L13. This research seeks to provide technical support and theoretical guidance for L13 to become a real commercial fungicide.
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Botrytis/crecimiento & desarrollo , Fungicidas Industriales/farmacología , Enfermedades de las Plantas/prevención & control , Solanum lycopersicum/crecimiento & desarrollo , Sulfonamidas/farmacología , Administración Cutánea , Administración Oral , Animales , Botrytis/efectos de los fármacos , Botrytis/metabolismo , Pared Celular/efectos de los fármacos , Farmacorresistencia Fúngica , Fungicidas Industriales/administración & dosificación , Fungicidas Industriales/efectos adversos , Solanum lycopersicum/microbiología , Microscopía Electrónica de Rastreo , Microscopía Electrónica de Transmisión , Estructura Molecular , Conejos , Ratas , Piel/efectos de los fármacos , Sulfonamidas/administración & dosificación , Sulfonamidas/efectos adversos , Vacuolas/efectos de los fármacos , Vacuolas/metabolismoRESUMEN
BACKGROUND: Although electroacupuncture is widely used in chronic pain management, it is quite controversial due to its unclear mechanism. We hypothesised that EA alleviates pain by inhibiting degradation of the ecto-nucleotidase prostatic acid phosphatase (PAP) and facilitating ATP dephosphorylation in dorsal root ganglions (DRGs). METHODS: We applied EA in male C57 mice subjected to chronic constriction injury (CCI) and assessed extracellular ATP and 5'-nucleotidease expression in DRGs. Specifically, we used a luminescence assay, quantitative reverse transcriptase-polymerase chain reaction, Western blotting, immunohistochemistry and nociceptive-related behavioural changes to gather data, and we tested for effects after PAP expression was inhibited with an adeno-associated virus (AAV). Moreover, membrane PAP degradation was investigated in cultured DRG neurons and the inhibitory effects of EA on this degradation were assessed using immunoprecipitation. RESULTS: EA treatment alleviated CCI surgery-induced mechanical pain hypersensitivity. Furthermore, extracellular ATP decreased significantly in both the DRGs and dorsal horn of EA-treated mice. PAP protein but not mRNA increased in L4-L5 DRGs, and inhibition of PAP expression via AAV microinjection reversed the analgesic effect of EA. Membrane PAP degradation occurred through a clathrin-mediated endocytosis pathway in cultured DRG neurons; EA treatment inhibited the phosphorylation of adaptor protein complex 2, which subsequently reduced the endocytosis of membrane PAP. CONCLUSIONS: EA treatment alleviated peripheral nerve injury-induced mechanical pain hypersensitivity in mice by inhibiting membrane PAP degradation via reduced endocytosis and subsequently promote ATP dephosphorylation in DRGs. SIGNIFICANCE: In a mouse model of chronic pain, electroacupuncture treatment increased levels of prostatic acid phosphatase (PAP: an ecto-nucleotidase known to relieve pain hypersensitivity) by inhibiting PAP degradation in dorsal root ganglions. This promoted extracellular ATP dephosphorylation, inhibited glia activation and eventually alleviated peripheral nerve injury-induced mechanical pain hypersensitivity in mice. Our findings represent an important step forward in clarifying the mechanisms of pain relief afforded by acupuncture treatment.
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Electroacupuntura , Neuralgia , Traumatismos de los Nervios Periféricos , Fosfatasa Ácida , Adenosina Trifosfatasas , Adenosina Trifosfato/metabolismo , Animales , Ganglios Espinales/metabolismo , Masculino , Ratones , Neuralgia/metabolismo , Neuralgia/terapia , Traumatismos de los Nervios Periféricos/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND: Major depressive disorder is characterized by a high risk of relapse. We aimed to compare the prophylactic effects of different antidepressant medicines (ADMs). METHODS: PubMed, Cochrane Central Register of Controlled Trials, Embase and the Web of Science were searched on 4 July 2019. A pooled analysis of parametric survival curves was performed using a Bayesian framework. The main outcomes were hazard ratios (HRs), relapse-free survival and mean relapse-free months. RESULTS: Forty randomized controlled trials were included. The 1-year relapse-free survival for ADM (76%) was significantly better than that for placebo (56%). Most of the relapse difference (86.5%) occurred in the first 6 months. Most HRs were not constant over time. Proof of benefit after 6 months of follow-up was not established partially because of small differences between the drug and placebo after 6 months. Almost all studies used an 'enriched' randomized discontinuation design, which may explain the high relapse rates in the first 6 months after randomization. CONCLUSIONS: The superiority of ADM v. placebo was mainly attributed to the difference in relapse rates that occurred in the first 6 months. Our analysis provided evidence that the prophylactic efficacy was not constant over time. A beneficial effect was observed, but the prevention of new episodes after 6 months was questionable. These findings may have implications for clinical practice.
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Trastorno Depresivo Mayor , Humanos , Trastorno Depresivo Mayor/tratamiento farmacológico , Trastorno Depresivo Mayor/prevención & control , Teorema de Bayes , Antidepresivos/uso terapéutico , Recurrencia , Enfermedad CrónicaRESUMEN
With the parallel and perpendicular components of high harmonics generated by using aligned N2 molecules, we propose a method to retrieve the alignment distribution induced by the aligning laser based on the quantitative rescattering theory. And the intensity of pump laser and gas temperature can be precisely determined as well. We find that the intensity ratio between two harmonic components is very sensitive to the inclusion of multiple-orbital contribution in the theory. We thus suggest that it could be used to identify the interference from inner orbitals by tuning input laser power or extending the spectral region of high harmonics.
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BACKGROUND: The development of prophylactic interventions for major depressive disorder (MDD) is an important issue in clinical practice. We aimed to compare the relative efficacy of nonpharmacological interventions for relapse prevention in adult patients with MDD. METHODS: Randomized controlled trials investigating nonpharmachological interventions for relapse prevention were included. A Bayesian network meta-analysis was performed. Hazard ratios are reported as effect sizes with 95% credible intervals. Global inconsistency, local inconsistency, heterogeneity, and transitivity were evaluated. Confidence for the results comparing the active treatment with control conditions or antidepressant medicine (ADM) was assessed. RESULTS: Thirty-six trials were included. Most nonpharmacological interventions were various forms of psychotherapy; others were noninvasive neurostimulation techniques (3 studies with electroconvulsive therapy and 1 study with transcranial magnetic stimulation). Psychotherapy as a monotherapy following ADM or psychotherapy produced significantly better outcomes than control conditions, and there was no significant difference between psychotherapy and ADM. The combination of psychotherapy and ADM was superior to either treatment alone. The results were similar for patients with at least 3 previous episodes. Neurostimulation techniques were also superior to controls, either as a monotherapy or combined with ADM. CONCLUSIONS: Our study provided evidence that psychotherapy as a monotherapy following ADM or psychotherapy was effective and performed as well as ADM for relapse prevention. Neurostimulation techniques also showed promising results but more studies are needed to confirm their efficacy. These findings may be informative for clinical practice and inspire future research.
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Trastorno Depresivo Mayor , Adulto , Antidepresivos/uso terapéutico , Teorema de Bayes , Trastorno Depresivo Mayor/tratamiento farmacológico , Trastorno Depresivo Mayor/prevención & control , Humanos , Metaanálisis en Red , Psicoterapia , Prevención SecundariaRESUMEN
Protein kinases C (PKCs) are a family of serine/threonine kinases involved in various cellular processes, including proliferation, differentiation, cell survival, and apoptosis. Here, we report the identification, structure-activity relationship (SAR), and 3D-QSAR studies of 69 natural indolocarbazoles, including 15 new compounds, from marine streptomyces strains. Interestingly, we found that the chair conformational isomer of 7-oxo-staurosporine (compound 15) inhibited PKCθ more potently than the corresponding boat isomer. An evaluation of kinase selectivity and antitumor efficacy revealed that 15 was a potent dual PKCθ/δ inhibitor and that it could efficiently inhibit tumor growth in pancreatic cancer (PC) by inducing cellular apoptosis and suppressing the NF-κB/p-P65 pathway. In addition, we demonstrated that overexpression of p-PKCδ and p-P65 was associated with poor survival rates in patients with PC, and p-PKCθ expression also showed significant positive correlations with p-PKCδ and p-P65 levels. Finally, the PC patient-derived xenograft model further confirmed the potential anti-PC efficacy of 15.
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Carbazoles/química , Proteína Quinasa C-delta/antagonistas & inhibidores , Proteína Quinasa C-theta/antagonistas & inhibidores , Inhibidores de Proteínas Quinasas/química , Animales , Apoptosis/efectos de los fármacos , Sitios de Unión , Carbazoles/metabolismo , Carbazoles/farmacología , Carbazoles/uso terapéutico , Línea Celular Tumoral , Cristalografía por Rayos X , Humanos , Ratones , Ratones Endogámicos BALB C , Simulación del Acoplamiento Molecular , FN-kappa B/metabolismo , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología , Proteína Quinasa C-delta/metabolismo , Proteína Quinasa C-theta/metabolismo , Inhibidores de Proteínas Quinasas/metabolismo , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Agua de Mar/microbiología , Transducción de Señal/efectos de los fármacos , Streptomyces/química , Streptomyces/metabolismo , Relación Estructura-Actividad , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
The long-term impact of human exploitation and environmental changes has led to a decline in grassland productivity and soil fertility, which eventually results in grassland degradation. The application of organic fertilizer is an effective improvement measure; however, it is still not fully understood how the addition of organic fertilizer influences grassland soil fertility and plant composition. A set of experiments were conducted in Inner Mongolia in China to reveal the tradeoff between steppe plants and soil microorganisms and the eco-physiological mechanisms involved, and how the addition of vermicompost and mushroom residues affect microbial diversity, enzyme activities, and the chemical properties of soil in degraded Leymus chinensis grassland. Organic fertilizer improved the soil nutrient status and shaped distinct bacterial communities. Compared with the control the available phosphorus (AP) and available potassium (AK) contents were highest under treatments a3 and b3, and the aboveground biomass was highest under the b3 treatment. Soil sucrase activities increased by 7.88% under the b3 treatment. Moreover, the richness index significantly increased by 7.07% and 7.23% under the a1 and b2 treatments, respectively. The most abundant Actinobacteria and Proteobacteria were detected in the organic fertilizer treatment. A linear discriminant analysis effect size (LEfSe) indicated that the bacterial community was significantly increased under the b3 treatment. A canonical correspondence analysis (RDA) and spearman correlation heatmap confirmed that total P (TP) and urease were the key driving factors for shaping bacterial communities in the soil. Our results indicated that the application of large amounts of vermicompost and mushroom residues increased the availability of nutrients and also enhanced the biodiversity of soil bacterial communities in L. chinensis grasslands, which will contribute to the sustainable development of agro-ecosystems.
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Bacterias/aislamiento & purificación , Fertilizantes , Microbiota , Nutrientes/análisis , Microbiología del Suelo , Bacterias/metabolismo , Biomasa , China , Pradera , Nutrientes/metabolismo , Suelo/químicaRESUMEN
Postoperative cognitive dysfunction increases mortality and morbidity in perioperative patients. Numerous studies have demonstrated that multiple surgery/anesthesia during the neurodevelopmental period affects cognitive function, whereas a single anesthesia/surgery rarely causes cognitive dysfunction in adults. However, whether adults who undergo multiple anesthesia/surgery over a short period will experience cognitive dysfunction remains unclear. In this study, central nervous system inflammation and changes in cholinergic markers were investigated in adult mice subjected to multiple laparotomy procedures over a short period of time. The results showed that despite the increased expression of IL-6 and TNF-α in the hippocampus after multiple operations and the activation of microglia, multiple anesthesia/surgery did not cause a decline in cognitive function in adult mice. There were no changes in the cholinergic markers after multiple anesthesia/surgery.
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Anestesia/métodos , Cirugía General/métodos , Animales , Western Blotting , Ensayo de Inmunoadsorción Enzimática , Técnica del Anticuerpo Fluorescente , Interleucina-10/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Microglía/metabolismo , Prueba del Laberinto Acuático de Morris , Distribución Aleatoria , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Monoclonal antibodies (mAbs) are large and have limitations as cancer therapeutics. Human single-chain variable fragment (scFv) is a small antibody as a good alternative. It can easily enter cancer tissues, has no immunogenicity and can be produced in bacteria to decrease the cost. The chemokine receptor CXCR4 is overexpressed in different cancer cells. It plays an important role in tumor growth and metastasis. Its overexpression is associated with poor prognosis in cancer patients and is regarded as an attractive target for cancer treatment. In this study, a peptide on the CXCR4 extracellular loop 2 (ECL2) was used as an antigen for screening a human scFv antibody library by yeast two-hybrid method. Three anti-CXCR4 scFv antibodies were isolated. They could bind to CXCR4 protein and three cancer cell lines (DU145, PC3, and MDA-MB-231) and not to 293T and 3T3 cells as negative controls. These three scFvs could decrease the proliferation, migration, and invasion of these cancer cells and promote their apoptosis. The two scFvs were further examined in a mouse xenograft model, and they inhibited the tumor growth. Tumor immunohistochemistry also demonstrated that the two scFvs decreased cancer cell proliferation and tumor angiogenesis and increased their apoptosis. These results show that these anti-CXCR4 scFvs can decrease cancer cell proliferation and inhibit tumor growth in mice, and may provide therapy for various cancers.
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PURPOSE: Various treatments have been investigated for Graves' ophthalmopathy (GO). We aimed to provide an overall profile of the efficacy and tolerability of various interventions for active and moderate to severe GO. METHODS: PubMed, Embase and the Cochrane Central Register of Controlled Trials were searched on 6 July 2018. Randomised controlled trials (RCT) investigating GO treatments were included. Two researchers independently extracted data according to a predefined form. A random effects network meta-analysis was performed using a frequentist approach. The primary outcome was efficacy, and the secondary outcome was tolerability (side effect discontinuation). RESULTS: Thirty-three studies with 1846 patients with GO were included. Orbital radiotherapy (ORT) plus intravenous glucocorticoids (IVGC) (OR 27.11; 95% CI 4.57 to 160.92), mycophenolate mofetil (MMF) (24.40, 95% CI 5.28 to 112.67), oral glucocorticoids (OGC) plus ciclosporin (20.22, 95% CI 1.60 to 255.20), IVGC plus MMF (12.08, 95% CI 2.96 to 49.35), teprotumumab (8.92, 95% CI 2.51 to 31.77), ORT plus OGC (4.88, 95% CI 1.25 to 19.06), rituximab (RTX) (4.85, 95% CI 1.18 to 19.86), somatostatin analogues (4.23, 95% CI 1.60 to 11.16), OGC plus azathioprine (AzA) (5.77, 95% CI 1.17 to 28.47) and IVGC (4.96, 95% CI 1.96 to 12.55) showed significantly better improvement than no treatment. ORT plus IVGC ranked first, followed by MMF. High heterogeneity and significant local inconsistency were observed in the RTX studies. The results of the sensitivity analyses were similar to those of the main analysis. CONCLUSION: A robust recommendation regarding the best treatment cannot be made, because most evidence was rated as low or very low quality according to the Grading of Recommendations, Assessment, Development and Evaluations framework. Large RCTs and individual participant data meta-analyses are necessary to confirm these results and explore potential moderators. PROPERO TRIAL REGISTRATION NUMBER: CRD42018103029.
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Oftalmopatía de Graves/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Azatioprina/uso terapéutico , Terapia Combinada , Ciclosporina/uso terapéutico , Glucocorticoides/uso terapéutico , Humanos , Ácido Micofenólico/uso terapéutico , Metaanálisis en Red , Radioterapia , Rituximab/uso terapéutico , Somatostatina/uso terapéuticoRESUMEN
Iron-manganese binary oxides (FeMnOx) can remove contaminants from aqueous solutions with high efficiency, and mesoporous silica (SBA-15) is widely used as a supporting material due to its large specific surface area and good stability. In this study, SBA-15 was used to support FeMnOx in the synthesis of a novel arsenic (As) adsorbent (FeMnOx/SBA-15), and its characteristics under different reaction conditions, such as pH, temperature, presence of competing ions, and humic acid, were tested. The results showed that the contaminant adsorption efficiency of the novel adsorbent was better than that of bare FeMnOx, as the addition of SBA-15 decreased the agglomeration effect of FeMnOx. Additionally, FeMnOx/SBA-15 underwent calcination to further enhance its performance. The state of iron and manganese in FeMnOx/SBA-15 and the corresponding arsenic removal efficiency were improved by calcination at 350⯰C with an FeMnOx/SBA-15 mass fraction of approximately 45%. Almost 90% of As (50â¯mL, 5.0â¯mgâ¯L-1) could be removed by 0.2â¯g L-1 of FeMnOx/SBA-15 (mass ratio of 45% and calcination temperature of 350⯰C). The FeMnOx/SBA-15 could regenerate and still be used after four consecutive cycles. The high As sorption capacity, ability to regenerate, and reusability of FeMnOx/SBA-15 confirmed that this adsorbent is promising for treating As-contaminated drinking water.