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Due to the extremely low C/N ratio, high concentration of ammonia nitrogen and refractory organic matter of mature landfill leachate (MLL), appropriate processes should be selected to effectively remove nitrogen and reduce disposal costs. Partial nitritation (PN) and anaerobic ammonia oxidation (AMX) have been used as the main nitrogen removal processes for MLL, and the sludge granulation in PN and AMX processes could contribute to high biological activity, good sedimentation performance, and stable resistance to toxicity. In this study, the O3-PN-AMX biogranules process was selected to effectively remove nitrogen from MLL without carbon addition and pH adjustment. Without uneconomical NH4+-N oxidation and wasting the alkalinity of MLL, ozone pretreatment achieved color removal, decreased humic- and fulvic-like acid substances, and alleviated the MLL toxicity on ammonia oxidizers. In addition, the ozonation of MLL could shorten the start-up time and improve the treatment efficiency and biogranules stability of PN and AMX processes. Efficient and stable nitritation was achieved in PN reactor without strict dissolved oxygen (DO) control, which was attributed to the unique structure of granular sludge, ozone pretreatment, and alternating inhibition of free ammonia and free nitric acid on nitrite oxidizers. Through the application of ozone pretreatment and granular sludge, the nitrogen removal rate (NRR) and nitrogen removal efficiency (NRE) of the O3-PN-AMX biogranules process reached 0.39 kg/m3/day and 85%, respectively, for the undiluted MLL treatment. This study might provide a novel and effective operation strategy of combined process for the efficient, economical, and stable nitrogen removal from MLL.
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Ozono , Contaminantes Químicos del Agua , Amoníaco , Oxidación Anaeróbica del Amoníaco , Reactores Biológicos , Desnitrificación , Nitrógeno/química , Oxidación-Reducción , Aguas del AlcantarilladoRESUMEN
To investigate the effect of electro-acupuncture therapy on limb spasm and excitability of motor neurons in stroke rats. Ischemic stroke model was induced with middle cerebral artery embolization in SD rats. Thirty-three modeled rats were randomly divided into model group, electro-acupuncture group, and baclofen group with 11 rats in each group, and another 10 rats were taken as sham operation group. The electro-acupuncture group and the baclofen group were treated with electro-acupuncture and baclofen tablets respectively. The model group and the sham operation group had no intervention. The neural function was evaluated with Bederson's scale and balance beam test; the muscle tension was measured with electrophysiography; the pathological changes of brain tissue was examined with HE staining; the content of glutamic acid (Glu) and γ-aminobutyric acid (GABA) in rat cerebral cortex was analyze with enzyme linked immunosorbent assay (ELISA) method, the expression of metabotropic glutamate receptor 1a () and γ-aminobutyric acid type B receptor subunit 1 () mRNA were detected with RTî-qPCR. Compared with the model group, the neurological function scores of the electro-acupuncture group and the baclofen group showed a downward trend at d7 after operation (all >0.05), and the neurological function scores of the electro-acupuncture group and the baclofen group were significantly decreased at d12 after the operation (all <0.05). Compared with sham operation group, the electrophysiological results of model group, electro-acupuncture group and baclofen group were significantly lower (all <0.05), and there was no statistical difference in the electrophysiological results of the model group, electro-acupuncture group and baclofen group at d7 after operation (all >0.05). Compared with the model group, the electrophysiological results of the electro-acupuncture group and baclofen group were significantly increased after operation (all <0.05). The results of HE staining showed that there was no cell edema and degeneration in the sham operation group, no pyknosis of the nucleus, and no bleeding in the interstitium. Cell edema and degeneration and mesenchymal congestion appeared in the model group. Compared with the model group, the cytoplasmic edema and degeneration and the interstitial bleeding in the electroacupuncture group and the baclofen group were reduced. Compared with sham operation group, the Glu content and the relative expression of mRNA was increased in the model group, electro-acupuncture group and baclofen group, while the GABA content and the relative expression of mRNA decreased (all <0.05). Compared with model group, the Glu content and the relative expression of mRNA in the electro-acupuncture group and baclofen group decreased, and the GABA content and relative expression of mRNA increased (all <0.05). Electro-acupuncture may improve limb spasm after stroke through regulating the expression of Glu and GABA in the cerebral cortex and the excitability of motor neurons in rats.
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Terapia por Acupuntura , Accidente Cerebrovascular , Animales , Neuronas Motoras , Ratas , Ratas Sprague-Dawley , Espasmo , Accidente Cerebrovascular/terapiaRESUMEN
Sphingosine kinase 1 (SphK1) is an oncogenic enzyme promoting transformation, proliferation, and angiogenesis of a number of human tumors. However, its effect on hepatocellular carcinoma (HCC) behavior has not been fully clarified. The purpose of this study was to determine the correlation between HCC and SphK1, and to evaluate the effect of SphK1 inhibitor N,N-dimethylsphingosine (DMS) in HCC. The expression of SphK1 was measured in tissue samples from 76 HCC and paired adjacent noncancerous liver tissues (NT) by immunohistochemistry, quantitative real-time PCR, and Western blotting analysis. The effect of DMS was tested on HCC cells by evaluating cell viability in vitro. Transwell cell migration and invasion assay were carried out for functional analysis. Furthermore, Western blotting analysis was performed to examine the impact of DMS on the PI3K/Akt/NF-kB signaling. High expression of Sphk1 was observed in 84.21% (64/76) of the HCC versus 15.79% (12/76) of the adjacent non-tumorous liver tissues; the difference of Sphk1 expression between HCC and the adjacent non-tumorous liver tissues was statistically significant (P < 0.001). The results were confirmed by Western blot analyses and quantitative real-time PCR. DMS inhibited the proliferation of SK-Hep1 and MHCCLM3 cells which have a relatively high level of SphK1 in a time- and concentration-dependent manner, and the invasion and migration of SK-Hep1 cells were distinctly suppressed after undergoing treatment with DMS. Furthermore, DMS markedly suppressed the expression of phosphorylations of Akt and NF-κB in HCC cells. Our data suggest that the pathogenesis of human HCC maybe mediated by Sphk1, and the specific Sphk1 inhibitor DMS can play a therapeutic role in the treatment of HCC and thus, Sphk1 could represent selective targets for the molecularly targeted treatments of HCC.
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Carcinoma Hepatocelular/tratamiento farmacológico , Proliferación Celular/efectos de los fármacos , Neoplasias Hepáticas/tratamiento farmacológico , FN-kappa B/antagonistas & inhibidores , Invasividad Neoplásica/prevención & control , Fosfotransferasas (Aceptor de Grupo Alcohol)/antagonistas & inhibidores , Esfingosina/análogos & derivados , Carcinoma Hepatocelular/metabolismo , Línea Celular , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Células Hep G2 , Humanos , Neoplasias Hepáticas/metabolismo , FN-kappa B/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Fosforilación/efectos de los fármacos , Fosfotransferasas (Aceptor de Grupo Alcohol)/metabolismo , Transducción de Señal/efectos de los fármacos , Esfingosina/farmacologíaRESUMEN
We describe here a novel method for integrating gene and miRNA expression profiles in cancer using feed-forward loops (FFLs) consisting of transcription factors (TFs), miRNAs and their common target genes. The dChip-GemiNI (Gene and miRNA Network-based Integration) method statistically ranks computationally predicted FFLs by their explanatory power to account for differential gene and miRNA expression between two biological conditions such as normal and cancer. GemiNI integrates not only gene and miRNA expression data but also computationally derived information about TF-target gene and miRNA-mRNA interactions. Literature validation shows that the integrated modeling of expression data and FFLs better identifies cancer-related TFs and miRNAs compared to existing approaches. We have utilized GemiNI for analyzing six data sets of solid cancers (liver, kidney, prostate, lung and germ cell) and found that top-ranked FFLs account for â¼20% of transcriptome changes between normal and cancer. We have identified common FFL regulators across multiple cancer types, such as known FFLs consisting of MYC and miR-15/miR-17 families, and novel FFLs consisting of ARNT, CREB1 and their miRNA partners. The results and analysis web server are available at http://www.canevolve.org/dChip-GemiNi.
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Regulación Neoplásica de la Expresión Génica , Redes Reguladoras de Genes , MicroARNs/metabolismo , Factores de Transcripción/metabolismo , Transcriptoma , Retroalimentación Fisiológica , Humanos , Neoplasias/genética , Neoplasias/metabolismoRESUMEN
Carbon recovery from waste activated sludge has been attracting considerable attention. However, the migration and transformation patterns of carbon sources between the phases have rarely been reported. In this study, a novel strategy using cation exchange resin (CER) coupled with sodium chloride (NaCl) to enhance carbon recovery through anaerobic fermentation (AF) was proposed. The results demonstrated that CER coupled with NaCl destroyed OH and CO stretching in amide I while promoting the formation of ß-sheet and random coil structures, leading to sludge disintegration. This significantly improved the kinetics of endogenous carbon release, resulting in the release of 1146.33 mg/L of carbon from the solid sludge into the liquid phase. Approximately 75.61 % of the initial carbon source was bio-transformed into short-chain fatty acids. Correspondingly, carbon recovery was significantly increased up to 852.23 mg C/L, 4.57 times that of the control. Mechanism exploration revealed that carbon source recovery was significantly elevated by the synergistic effect of CER and NaCl. CER effectively removed high-valence cations from extracellular polymeric substance (EPS), weakening its bridging and adsorption-electro neutralization capabilities, promoting protein deflocculation, and triggering EPS disruption to release extracellular carbon sources. NaCl disrupted the ionic strength and distribution inside and outside microbial cells, creating an osmotic pressure difference that resulted in cell plasmolysis and lysis, ultimately inducing the release of intracellular carbon sources. Economic and carbon emission reduction benefit analyses verified that the CER coupled with NaCl pretreatment is a cost-effective sludge treatment strategy. This study illustrates the carbon source migration and transformation pathways in the CER coupled with NaCl-assisted AF process, providing guidance for sustainable sludge management.
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Carbono , Fermentación , Aguas del Alcantarillado , Cloruro de Sodio , Aguas del Alcantarillado/química , Anaerobiosis , Cloruro de Sodio/química , Resinas de Intercambio de Catión , Eliminación de Residuos Líquidos/métodos , Reactores BiológicosRESUMEN
Decoupling of crop-livestock systems increases the risks of pollution, waste of nutrient resources, and biodiversity loss. Crop-livestock integration (CLI) is an effective solution to these problems, and motivating farmers to adopt CLI is the key. Many countries have implemented environmental regulations (ER) aiming to influence farmers' CLI adoption decisions. Based on a field study of 316 hog farmers from Shaanxi Province of China, this paper applies the triple-hurdle model to empirically examine the impacts of economic expectations (EE) and ER on CLI adoption decisions. It also verifies the income effect of CLI. The results are as follows: 90.5% of farmers are willing to adopt CLI, but the adoption rate is only 40.8% and the average integration degree is only 0.236; CLI not been widely popularized. EE and ER promote farmers' CLI adoption significantly, while the impact of interaction between EE and ER on CLI adoption differs. IER weakens the positive impact of EE on farmers' CLI integration degree, which has a "crowding out effect." GER negatively moderates the impact of EE on farmers' adoption willingness of CLI. CER strengthens the positive effect of EE on farmers' adoption behavior and CLI integration degree. CLI increases the farmers' income. These results contribute to our understanding of the mechanisms of CLI adoption decisions and sustainable policy optimization for green agricultural development.
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Agricultores , China , Animales , Productos Agrícolas , Ganado , Agricultura , HumanosRESUMEN
Ionizing radiation (IR) induces ferroptosis in head and neck squamous cell carcinoma (HNSCC). But, it remains unclear whether ferroptosis affects the prognosis of HNSCC patients after receiving radiotherapy. This study aims to develop a ferroptosis signature to predict the radiosensitivity and prognosis of HNSCC. Ferroptosis-related genes, clinical data and RNA expression profiles were obtained from the FerrDb database, The Cancer Genome Atlas and GEO database. Prognostic genes were identified by random survival forest, univariate Cox regression, Kaplan-Meier and ROC analyses. Principal component analysis, multivariate Cox regression, nomogram and DCA analyses were conducted to estimate its predictive ability. Functional enrichment and immune-related analyses were performed to explore potential biological mechanisms and tumor immune microenvironment. The effect of the hub gene on ferroptosis and radiosensitivity was verified using flow cytometry, quantitative real-time PCR and clonogenic survival assay. We constructed a ferroptosis-related signature, including IL6, NCF2, metadherin (MTDH) and CBS. We classified patients into high-risk (HRisk) and low-risk groups according to the risk scores. The risk score was confirmed to be an independent predictor for overall survival (OS). Combining the clinical stage with the risk score, we established a predictive nomogram for OS. Furthermore, pathways related to tumorigenesis and tumor immune suppression were mainly enriched in HRisk. MTDH was verified to have a potent effect on IR-induced ferroptosis and consequently promoted radiosensitivity. We constructed a ferroptosis-related signature to predict radiosensitivity and OS in HNSCC patients. MTDH was identified as a promising therapeutic target in radioresistant HNSCC patients.
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Ferroptosis , Neoplasias de Cabeza y Cuello , Humanos , Pronóstico , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/radioterapia , Ferroptosis/genética , Factores de Transcripción , Tolerancia a Radiación/genética , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/radioterapia , Microambiente Tumoral , Proteínas de la Membrana/genética , Proteínas de Unión al ARNRESUMEN
BACKGROUND: The clinical management of chronic myeloid leukemia (CML) patients requires the identification of the type of BCR::ABL1 transcript at diagnosis and the monitoring of its expression and potential tyrosine kinase inhibitor (TKI) resistance mutations during treatment. Detection of resistant mutation requires transcript type-specific amplification of BCR::ABL1 from RNA. METHODS: In this study, a custom RNA-based next-generation sequencing (NGS) assay (Dup-Seq BCR::ABL1) that enables (a) the identification of BCR::ABL1 transcript type and (b) the detection of resistance mutations from common and atypical BCR::ABL1 transcript types was developed and validated. The assay design covers BCR exon 1 to ABL1 exon 10 and employs duplicate PCR amplification for error correction. The custom data analysis pipeline enables breakpoint determination and overlapped mutation calling from duplicates, which minimizes the low-level mutation artifacts. RESULTS: This study demonstrates that this novel assay achieves high accuracy (positive percent agreement (PPA) for fusion: 98.5%; PPA and negative percent agreement (NPA) for mutation at 97.8% and 100.0%, respectively) and sensitivity (limit of detection (LOD) for mutation detection at 3% from 10 000 copies of BCR::ABL1 input). CONCLUSIONS: The Dup-Seq BCR::ABL1 assay not only allows for the identification of BCR::ABL1 typical and atypical transcript types and accurate and sensitive detection of TKI-resistant mutations but also simplifies molecular testing work flow for the clinical management of CML patients.
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Radiation therapy is a primary treatment for cancer, but radioresistance remains a significant challenge in improving efficacy and reducing toxicity. Accumulating evidence suggests that deubiquitinases (DUBs) play a crucial role in regulating cell sensitivity to ionizing radiation. Traditional small-molecule DUB inhibitors have demonstrated radiosensitization effects, and novel deubiquitinase-targeting chimeras (DUBTACs) provide a promising strategy for radiosensitizer development by harnessing the ubiquitin-proteasome system. This review highlights the mechanisms by which DUBs regulate radiosensitivity, including DNA damage repair, the cell cycle, cell death, and hypoxia. Progress on DUB inhibitors and DUBTACs is summarized, and their potential radiosensitization effects are discussed. Developing drugs targeting DUBs appears to be a promising alternative approach to overcoming radioresistance, warranting further research into their mechanisms.
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Antineoplásicos , Neoplasias , Humanos , Antineoplásicos/uso terapéutico , Inhibidores de Proteasoma/farmacología , Inhibidores de Proteasoma/uso terapéutico , Neoplasias/radioterapia , Neoplasias/tratamiento farmacológico , Enzimas Desubicuitinizantes/metabolismo , Tolerancia a RadiaciónRESUMEN
OBJECTIVE: To explore the levels of regulatory T cells (Tregs) and cytokines IL-35, TGF-ß and IL-10 in peripheral blood of hemophilia A(HA) patients with Fâ § inhibitor and their clinical significance. METHODS: 43 HA patients admitted to the Hematology Department of the Affiliated Hospital of North China University of Science and Technology from October 2019 to December 2020 were selected, including 6 cases with Fâ § inhibitor and 37 cases without Fâ § inhibitor. In addition, 20 healthy males who underwent physical examinations were selected as healthy controls. Flow cytometry was used to detect the levels of CD4 + CD25 + CD127 - Tregs in peripheral blood of the HA patients and healthy controls, and ELISA assay was used to detect the expression levels of IL-35, TGF-ß and IL-10 in serum, and their differences between different groups were compared. RESULTS: Compared with the healthy control group, the level of Tregs in HA patients was decreased, and the level of Tregs in the Fâ § inhibitor positive group was the lowest, the difference was statistically significant (P <0.05). There was no significant difference in the expression level of Tregs in HA patients of different severity levels. The serum IL-35, TGF-ß, and IL-10 levels in both Fâ § inhibitor negative and positive groups were significantly lower than those in healthy control group, and those in Fâ § inhibitor positive group were significantly lower than those in Fâ § inhibitor negative group (all P <0.05). CONCLUSION: The decrease of Tregs, IL-35, TGF-ß, and IL-10 levels in HA patients may be related to the formation of Fâ § inhibitors.
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Hemofilia A , Interleucina-10 , Interleucinas , Linfocitos T Reguladores , Factor de Crecimiento Transformador beta , Humanos , Interleucina-10/sangre , Hemofilia A/sangre , Factor de Crecimiento Transformador beta/sangre , Interleucinas/sangre , Masculino , Estudios de Casos y Controles , Relevancia ClínicaRESUMEN
Background: Frail elderly patients with newly diagnosed multiple myeloma (NDMM) have inferior survival and less benefit from high-dose therapies. This prospective study aimed to investigate the efficacy, safety, and quality of life (QoL) of induction treatment of ixazomib/lenalidomide/dexamethasone (IRd) and ixazomib/pegylated liposomal doxorubicin/dexamethasone (IDd) followed by ixazomib/dexamethasone (Id) maintenance therapy in frail, elderly patients with NDMM. Methods: From July 2019 to December 2021, this non-randomized concurrent controlled clinical study enrolled 120 NDMM patients aged ≥65 years with frailty defined by the International Myeloma Working Group (IMWG) frailty score or Mayo geriatric scoring system. The enrolled patients received 6-8 cycles of IRd or IDd followed by Id maintenance therapy for a minimum of 2 years at the discretion of physicians based on patient's clinical characteristics (chiCTR1900024917). Findings: The median age was 71 years and 55% of the patients were males. The overall response rate (ORR) was 82% and 77%, complete response (CR) rate was 25% and 12% for IRd and IDd groups, respectively. The difference in ORR of the Idd group minus the IRd group was -5.36% (95% CI: -18.9% to 8.19%), indicating that the ORR of the IDd group was neither inferior nor non-inferior to the IRd group. After a median follow-up of 34.3 months, the median progression-free survival (PFS) was 21.6 and 13.9 months, OS was not reached and 29.2 months in IRd and IDd groups, respectively. 28 and 33 patients discontinued induction therapy, 20 and 19 discontinued maintenance therapy in IRd and IDd groups, respectively. Cumulative Grade 3 or higher hematological adverse events (AEs) occurred in 10 of the 60 patients (17%) and non-hematological AEs occurred in 15 of the 60 patients (25%) in the IRd group, while 13 of the 60 patients (22%) and 21 of the 60 patients (35%) in the IDd group. Patients were observed with clinically significant improvement in QoL when compared with that at baseline in both IRd and IDd groups by evaluation per cycle (P < 0.0001). Interpretation: The results demonstrated that compared with IRd regimen, IDd regimen showed no significant advantage, but the survival of the IDd group was shorter than that of the IRd group, indicating an all-oral outpatient triplet regimen with IRd, which has low toxicity and has improved QoL, could be the viable first-line treatment option for frail NDMM patients. Funding: The Young Elite Scientist sponsorship program by bast of Beijing Association for Science and Technology (No. BYESS2023116) and Beijing Medical Award Foundation (No. YXJL-2018-0539-0073).
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BACKGROUND: Sovleplenib, a novel spleen tyrosine kinase (SYK) inhibitor, showed promising safety and activity in patients with primary immune thrombocytopenia in a phase 1b/2 trial. We aimed to evaluate the efficacy and safety of sovleplenib in patients with chronic primary immune thrombocytopenia. METHODS: This randomised, double-blind, placebo-controlled, phase 3 trial (ESLIM-01) was done in 34 clinical centres in China. Eligible patients, aged 18-75 years, had chronic primary immune thrombocytopenia, an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and received one or more previous treatments. Patients were randomly assigned (2:1) to receive oral sovleplenib or placebo, 300 mg once daily, for 24 weeks. Randomisation was stratified by baseline platelet counts, previous splenectomy, and concomitant treatment for anti-immune thrombocytopenia at baseline. The primary endpoint was durable response rate (proportion of patients with a platelet count of ≥50â×â109/L on at least four of six scheduled visits between weeks 14 and 24, not affected by rescue treatment) assessed by intention-to-treat. The trial is registered with ClinicalTrials.gov, NCT05029635, and the extension, open-label phase is ongoing. FINDINGS: Between Sept 29, 2021, and Dec 31, 2022, 188 patients were randomly assigned to receive sovleplenib (n=126) or placebo (n=62). 124 (66%) were female, 64 (34%) were male, and all were of Asian ethnicity. Median previous lines of immune thrombocytopenia therapy were 4·0, and 134 (71%) of 188 patients had received previous thrombopoietin or thrombopoietin receptor agonist. The primary endpoint was met; durable response rate was 48% (61/126) with sovleplenib compared with zero with placebo (difference 48% [95% CI 40-57]; p<0·0001). The median time to response was 8 days with sovleplenib compared with 30 days with placebo. 125 (99%) of 126 patients in the sovleplenib group and 53 (85%) of 62 in the placebo group reported treatment-emergent adverse events (TEAEs), and most events were mild or moderate. Frequent TEAEs of grade 3 or higher for sovleplenib versus placebo were platelet count decreased (7% [9/126] vs 10% [6/62]), neutrophil count decreased (3% [4/126] vs 0% [0/62]), and hypertension (3% [4/126] vs 0% [0/62]). Incidences of serious TEAEs were 21% (26/126) in the sovleplenib group and 18% (11/62) in the placebo group. There were no deaths in the study. INTERPRETATION: Sovleplenib showed a clinically meaningful sustained platelet response in patients with chronic primary immune thrombocytopenia, with a tolerable safety profile and improvement in quality of life. Sovleplenib could be a potential treatment option for patients with immune thrombocytopenia who received one or more previous therapy. FUNDING: HUTCHMED and Science and Technology Commission of Shanghai Municipality.
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Púrpura Trombocitopénica Idiopática , Humanos , Persona de Mediana Edad , Masculino , Femenino , Método Doble Ciego , Adulto , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , China , Anciano , Resultado del Tratamiento , Enfermedad Crónica , Adulto Joven , Adolescente , Recuento de Plaquetas , Quinasa Syk/antagonistas & inhibidores , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/efectos adversosRESUMEN
Dysregulation of autophagy, a cellular catabolic mechanism essential for degradation of misfolded proteins, has been implicated in multiple neurodegenerative diseases. However, the mechanisms that lead to the autophagy dysfunction are still not clear. Based on the results of a genome-wide screen, we show that reactive oxygen species (ROS) serve as common mediators upstream of the activation of the type III PI3 kinase, which is critical for the initiation of autophagy. Furthermore, ROS play an essential function in the induction of the type III PI3 kinase and autophagy in response to amyloid beta peptide, the main pathogenic mediator of Alzheimer's disease (AD). However, lysosomal blockage also caused by Abeta is independent of ROS. In addition, we demonstrate that autophagy is transcriptionally down-regulated during normal aging in the human brain. Strikingly, in contrast to normal aging, we observe transcriptional up-regulation of autophagy in the brains of AD patients, suggesting that there might be a compensatory regulation of autophagy. Interestingly, we show that an AD drug and an AD drug candidate have inhibitory effects on autophagy, raising the possibility that decreasing input into the lysosomal system may help to reduce cellular stress in AD. Finally, we provide a list of candidate drug targets that can be used to safely modulate levels of autophagy without causing cell death.
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Envejecimiento/genética , Enfermedad de Alzheimer/patología , Autofagia/genética , Encéfalo/fisiología , Estudio de Asociación del Genoma Completo , Enfermedad de Alzheimer/genética , Péptidos beta-Amiloides/metabolismo , Encéfalo/patología , Regulación de la Expresión Génica , Humanos , Lisosomas/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Accurately assessing the impact of low-carbon urban construction on green economic development has great significance for achieving economic development with environmental protection, and for building an ecological civilization and a beautiful China. Based on panel data for 271 cities in China from 2004 to 2019, multi-period and spatial difference-in-difference econometric models were used to comprehensively investigate the impact of three batches of low-carbon city pilot policies on green economic development, finding the following: The contribution of low-carbon urban construction on urban green economic development is significant and positive, and still holds under a series of robustness tests. Parallel trend tests also show a lag in the policy effect, and the effect is strengthened over policy implementation time. Green orientation of technological progress, green transformation of industry, and green upgrade of consumption are important channels for the effect of the policies. The promotion effect of low-carbon city construction is stronger in the central and northern cities, and in cities with high green economic development, than in western and southern cities, and those with low green economic development. Construction of low-carbon pilot cities not only promotes their own green economic development, but also that in neighboring cities, exerting a demonstration effect. This effect is greater in urban areas. This study provides empirical support for policy planning to promote low-carbon urban construction across the country.
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Carbono , Desarrollo Económico , Ciudades , China , PolíticasRESUMEN
Lotus-seedpod structured Li2ZnTi3O8/C (P-LZTO) microspheres obtained by the molten salt method are reported for the first time. The received phase-pure Li2ZnTi3O8 nanoparticles are inserted into the carbon matrix homogeneously to form a Lotus-seedpod structure, as confirmed by the morphological and structural measurements. As the anode for lithium-ion batteries, the P-LZTO material demonstrates excellent electrochemical performance with a high rate capacity of 193.2 mAh g-1 at 5 A g-1 and long-term cyclic stability up to 300 cycles at 1 A g-1. After even 300 cyclings, the P-LZTO particles can maintain their morphological and structural integrity. The superior electrochemical performances have arisen from the unique structure where the polycrystalline structure is beneficial for shorting the lithium-ion diffusion path, while the well-encapsulated carbon matrix can not only enhance the electronic conductivity of the composite but also alleviate the stress anisotropy during lithiation/delithiation process, leading to well-preserved particles.
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Myelodysplastic syndrome (MDS) is a common hematological malignant disease, characterized by malignant hematopoietic stem cell proliferation in the bone marrow (BM); clinically, it mainly manifests clinically mainly by as pathological hematopoiesis, hemocytopenia, and high-risk transformation to acute leukemia. Several studies have shown that the BM microenvironment plays a critical role in the progression of MDS. In this study, we specifically evaluated mesenchymal stromal cells (MSCs) that exert immunomodulatory effects in the BM microenvironment. This immunomodulatory effect occurs through direct cell-cell contact and the secretion of soluble cytokines or micro vesicles. Several researchers have compared MSCs derived from healthy donors to low-risk MDS-associated bone mesenchymal stem cells (BM-MSCs) and have found no significant abnormalities in the MDS-MSC phenotype; however, these cells have been observed to exhibit altered function, including a decline in osteoblastic function. This altered function may promote MDS progression. In patients with MDS, especially high-risk patients, MSCs in the BM microenvironment regulate immune cell function, such as that of T cells, B cells, natural killer cells, dendritic cells, neutrophils, myeloid-derived suppressor cells (MDSCs), macrophages, and Treg cells, thereby enabling MDS-associated malignant cells to evade immune cell surveillance. Alterations in MDS-MSC function include genomic instability, microRNA production, histone modification, DNA methylation, and abnormal signal transduction and cytokine secretion.
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Leucemia Mieloide Aguda , Células Madre Mesenquimatosas , Síndromes Mielodisplásicos , Humanos , Síndromes Mielodisplásicos/genética , Médula Ósea/patología , Células de la Médula Ósea/patología , Leucemia Mieloide Aguda/patología , Microambiente TumoralRESUMEN
Objective: To determine the effect of the autophagy inhibitor, 3-methyladenine (3-MA), on cognitive function changes, microglia activity, neuronal apoptosis, and inflammation in rats following radiation-induced brain injury. Methods: The following groups were established: control, model, and 3-MA. A rat model of radiation-induced brain injury was generated with a medium dose of X-rays. A Morris water maze was used to observe the cognitive function of the rats. H&E staining was used to observe the pathological changes in the hippocampus. The morphological and quantitative changes of neuronal nuclear (NeuN)-positive neurons and Iba-1-positive microglia in the ipsilateral hippocampus were analyzed by immunohistochemistry. Western blot analysis was done to measure the changes of NeuN ionized calcium binding adapter molecule 1(Iba-1) and apoptosis-related proteins. Immunofluorescence staining of Iba-1 and Microtuble-associated protein light chain 3 (LC3) was done to evaluate the changes in microglia autophagy. TUNEL staining was used to detect apoptosis in the hippocampus. Enzyme-Linked Immunosorbent Assay was used to detect the levels of TNF-α and IL-6 as a measure of the inflammatory response in the hippocampus. Results: After irradiation, the nucleus of the neurons in the hippocampus was constricted, the pyramidal tract structure was disordered, neuronal apoptosis was increased (P < .001), the expression of microglia increased (P < .01), autophagy was increased (P < .05), and conversion of microglia to the M2 type increased (P < .05). After 3-MA administration, the level of autophagy decreased (P < .05), the damage to the hippocampal region was reduced, neuronal apoptosis decreased (P < .01), and the activity of the microglia decreased (P < .01). Conclusion: Radiation can active the Microglia. 3-MA inhibits autophagy and excessive activity in microglia, and promotes the conversion of microglia from the M1 to the M2 type, thereby promoting the recovery of brain tissue following radiation exposure.
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Tumor-initiating cells (TICs) with stem-like cell properties initiate and sustain progressive growth, resulting in a heterogeneous tumor mass. The survival and growth of tumors rely on the development of a vasculature to provide nutrients and oxygen. Crosstalk between TICs and vascularization may be one of the central players in the initiation, long-term maintenance, and progression of tumors. This review surveys current evidence concerning the crosstalk that occurs in tumor/stromal interactions, including genetic change, vascular niche, hypoxia, and dormancy of tumors. A better understanding of this crosstalk might help provide the basis for developing more effective therapeutic drug targets.
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Neoplasias/irrigación sanguínea , Neoplasias/patología , Células Madre Neoplásicas/patología , Neovascularización Patológica/patología , Animales , HumanosRESUMEN
Recently, research interest in the application of lignin is growing, especially as adsorbent material. However, single lignin shows unsatisfactory adsorption performance, and thus, construction of lignin-based nanocomposites is worth considering. Herein, we introduced graphene oxide (GO) into lignin to form lignin/GO (LGNs) composite nanospheres by a self-assembly method. FTIR and 1H NMR spectroscopy illustrated that lignin and GO are tightly connected by hydrogen bonds. The LGNs as an environmental friendly material, also exhibit excellent performance for Cr(vi) removal. The maximum sorption capacity of LGNs is 368.78 mg g-1, and the sorption efficiency is 1.5 times than that of lignin nanospheres (LNs). The removal process of Cr(vi) via LGNs mainly relies on electrostatic interaction, and it also involves the reduction of Cr(vi) to Cr(iii). Moreover, LGNs still have high adsorption performance after repeating five times with the sorption capacity of 150.4 mg g-1 in 200 mg g-1 Cr(vi) solution. Therefore, the prepared lignin-GO composite nanospheres have enormous potential as a low-cost, high-absorbent and recyclable adsorbent, and can be used in wastewater treatment.
RESUMEN
The treatment for large artery atherosclerosis (LAA) stroke is also important for patients with cerebral small vessel disease (SVD). Our aim is to clarify the risk factors for ischemic cerebral SVD and to evaluate the different risk factor profiles of the two ischemic stroke subtypes, namely, ischemic cerebral SVD and LAA. A total of 353 patients with acute ischemic stroke were assigned to two groups according to the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) criteria: the ischemic cerebral SVD group and the LAA group. A total of 70 non-stroke patients admitted during the same period served as the control group. Clinical variables were collected, including age, sex, blood pressure, blood glucose, triglycerides, low-density lipoprotein, total cholesterol (TC), smoking history, drinking history, coronary atherosclerotic heart disease and family history of a high-risk disease. Multivariate logistic regression (MLR) analyses were performed. MLR analysis showed that risk factors for LAA stroke included hypertension, diabetes mellitus, high low-density lipoprotein, hypertriglyceridemia and smoking compared with the control group. The analysis also showed that the risk factors for cerebral SVD stroke were hypertension, diabetes mellitus, high TC, hypertriglyceridemia and smoking. In terms of the factors distinguishing LAA and cerebral SVD, MLR demonstrated that high TC played prominent roles in cerebral SVD. Hypertension, diabetes mellitus, high total cholesterol, hypertriglyceridemia and smoking are independent risk factors for cerebral SVD stroke. Compared with the LAA stroke group, patients with cerebral SVD stroke were more likely to have a high level of TC.