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1.
Nature ; 626(8000): 742-745, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38383623

RESUMO

Observationally, kilonovae are astrophysical transients powered by the radioactive decay of nuclei heavier than iron, thought to be synthesized in the merger of two compact objects1-4. Over the first few days, the kilonova evolution is dominated by a large number of radioactive isotopes contributing to the heating rate2,5. On timescales of weeks to months, its behaviour is predicted to differ depending on the ejecta composition and the merger remnant6-8. Previous work has shown that the kilonova associated with gamma-ray burst 230307A is similar to kilonova AT2017gfo (ref. 9), and mid-infrared spectra revealed an emission line at 2.15 micrometres that was attributed to tellurium. Here we report a multi-wavelength analysis, including publicly available James Webb Space Telescope data9 and our own Hubble Space Telescope data, for the same gamma-ray burst. We model its evolution up to two months after the burst and show that, at these late times, the recession of the photospheric radius and the rapidly decaying bolometric luminosity (Lbol ∝ t-2.7±0.4, where t is time) support the recombination of lanthanide-rich ejecta as they cool.

2.
Kaohsiung J Med Sci ; 39(11): 1062-1076, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37698263

RESUMO

To investigate the biological role and mechanism of circ_0084188 in colorectal cancer (CRC). Real-time quantitative polymerase chain reaction and western blot assay were used to detect RNA levels and protein levels in CRC cell lines (HCT116 and SW480), respectively. Cell proliferation was evaluated by Cell Counting Kit-8 assay, 5-ethynyl-2'-deoxyuridine assay, and colony formation assays. Cell apoptosis was determined using flow cytometry. Cell migration and invasion were measured by transwell assay. Sphere formation efficiency was determined by sphere formation assay. The interaction between microRNA-654-3p (miR-654-3p) and circ_0084188 or Kruppel-like factor 12 (KLF12) was confirmed by a dual-luciferase reporter, RNA immunoprecipitation and RNA pull-down assays. Xenograft in CRC mice model was utilized for exploring the role of circ_0084188 in vivo.Circ_0084188 was overexpressed in CRC tissues and cells. Circ_0084188 silencing suppressed cell proliferation, migration, invasion, and stemness and induced apoptosis in CRC cells. Circ_0084188 acted as a sponge for miR-654-3p, and circ_0084188 regulated CRC cell behaviors via sponging miR-654-3p. Moreover, KLF12 was a target of miR-654-3p, and miR-654-3p overexpression inhibited the malignant behaviors of CRC cells by downregulating KLF12. Mechanically, circ_0084188 sponged miR-654-3p to regulate KLF12 expression in CRC cells. In addition, circ_0084188 downregulation inhibited tumor growth in vivo.Circ_0084188 knockdown might repress CRC progression partially via regulating the miR-654-3p/KLF12 axis, providing a novel insight into the pathogenesis of CRC.


Assuntos
Neoplasias Colorretais , MicroRNAs , Animais , Humanos , Camundongos , Apoptose/genética , Western Blotting , Linhagem Celular Tumoral , Proliferação de Células/genética , Neoplasias Colorretais/genética , Fatores de Transcrição Kruppel-Like/genética , MicroRNAs/genética , RNA Circular/genética
3.
Integr Cancer Ther ; 22: 15347354231188679, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37565358

RESUMO

BACKGROUND: Aromatase inhibitors (AIs) are recommended as the preferred therapy for postmenopausal women with hormone receptor-positive (HR+) breast cancer. As a result, aromatase inhibitor-associated musculoskeletal symptom (AIMSS) have become a major problem leading to therapy discontinuation and decreased quality of life in patients receiving adjuvant AIs treatment. Multiple therapies have been attempted, but have yielded limited clinical results. This study will be performed to determine whether acupoint thread embedding (ATE) combined with Wenshen Bugu Decoction can effectively treat AIMSS, so as to improve the AIs medication compliance of postmenopausal breast cancer patients. METHODS: This study will utilize a randomized, 2 parallel groups controlled trial design. A total of 128 eligible postmenopausal breast cancer women with AIMSS will be randomized to receive a 12-week treatment with Wenshen Bugu Decoction alone (control group) or in combination with ATE (treatment group) in a 1:1 ratio. The primary outcome will be the 12 week Brief Pain Inventory Worst Pain (BPI-WP) score. The secondary outcome measures will include response rate, Brief Pain Inventory-Short Form (BFI-SF), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Functional Assessment of Cancer Therapy-Endocrine Symptom (FACT-ES), Functional Assessment of Cancer Therapy-Breast (FACT-B), bone marrow density (BMD), blood markers of bone metabolite, Morisky medication adherence scale-8 (MMAS-8), credibility and expectancy, and survival outcomes. DISCUSSION: This trial may provide clinical evidence that ATE combined with Wenshen Bugu Decoction can be beneficial for treating AIMSS among postmenopausal breast cancer survivors. Our findings will be helpful to enhance the quality of life and reduce the occurrence of AIs withdrawal.


Assuntos
Inibidores da Aromatase , Neoplasias da Mama , Humanos , Feminino , Inibidores da Aromatase/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/complicações , Qualidade de Vida , Pontos de Acupuntura , Pós-Menopausa , Dor/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto
4.
J Am Chem Soc ; 145(16): 9233-9241, 2023 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-37043290

RESUMO

A new strategy focusing on the last-stage asymmetric assembly of the ring D, which inherently possesses the densest part of stereogenic centers and functional groups in the A/B/C/D ring system of (-)-cephalotaxine, has been developed, in which a novel Rh-catalyzed asymmetric (2 + 3) annulation of tertiary enamides with enoldiazoacetates is designed and explored for enantioselective construction of the crucial cyclopentane ring D bearing a unique spirocyclic aza-quaternary stereocenter. Based on the expeditious access of chiral functionalized building block with the tetracyclic A/B/C/D ring system, a concise enantioselective total synthesis of (-)-cephalotaxine starting from readily available homopiperonyl alcohol has been achieved in nine steps with only two column chromatography purifications. Following the tactical introduction of the Meinwald rearrangement, enantioselective divergent syntheses of (-)-cephalotine B with an additional C3-O-C11 oxo-bridged bond (14 steps), (-)-fortuneicyclidin B with an unprecedented C3-C10 bond (14 steps), and its 2-epimer (-)-fortuneicyclidin A (16 steps) have been also accomplished for the first time.

5.
Nature ; 612(7939): 232-235, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36477130

RESUMO

It is generally believed that long-duration gamma-ray bursts (GRBs) are associated with massive star core collapse1, whereas short-duration GRBs are associated with mergers of compact star binaries2. However, growing observations3-6 have suggested that oddball GRBs do exist, and several criteria (prompt emission properties, supernova/kilonova associations and host galaxy properties) rather than burst duration only are needed to classify GRBs physically7. A previously reported long-duration burst, GRB 060614 (ref. 3), could be viewed as a short GRB with extended emission if it were observed at a larger distance8 and was associated with a kilonova-like feature9. As a result, it belongs to the type I (compact star merger) GRB category and is probably of binary neutron star (NS) merger origin. Here we report a peculiar long-duration burst, GRB 211211A, whose prompt emission properties in many aspects differ from all known type I GRBs, yet its multiband observations suggest a non-massive-star origin. In particular, substantial excess emission in both optical and near-infrared wavelengths has been discovered (see also ref. 10), which resembles kilonova emission, as observed in some type I GRBs. These observations point towards a new progenitor type of GRBs. A scenario invoking a white dwarf (WD)-NS merger with a post-merger magnetar engine provides a self-consistent interpretation for all the observations, including prompt gamma rays, early X-ray afterglow, as well as the engine-fed11,12 kilonova emission.


Assuntos
Raios gama
7.
Chem Commun (Camb) ; 58(62): 8710-8713, 2022 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-35833607

RESUMO

The unique reactivity of indolyl-substituted p-QMs as a new type of two-carbon synthon has been explored for the first time in a novel iron(III)-catalyzed tandem annulation. This (2+2) annulation/retro-4π electrocyclization/imino-Nazarov cyclization cascade reaction is characterized by an unusual structural reconstruction of indolyl-substituted p-QMs, leading to an expeditious assembly of synthetically important functionalized cyclopenta[b]indoles.


Assuntos
Indóis , Ferro , Catálise , Ciclização , Indolquinonas , Indóis/química
8.
Phytochemistry ; 200: 113223, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35513134

RESUMO

Dendrobium officinale Kimura et Migo, one of the most important orchids because of its medicinal and edible value, has a typical Dendrobium Sw. flora scent, which has great application potential and commercial value to be characterized. The aroma-active compounds originating from D. officinale fresh flowers (DFF) were investigated using a sensomics approach. A combined solid phase microextraction and solvent-assisted flavor evaporation method were used to accurately capture the overall aromatic profile. Exactly 34 odorants were detected and identified by aroma extract dilution analysis (AEDA) coupled with gas chromatography/olfactometry-mass spectrometry (GC/O-MS) in DFF, of which nine odorants had a flavor dilution (FD) factor ≥27. All 34 odorants were further quantified. The odor activity values (OAVs) were calculated with the highest value of 7444, in which 18 compounds were confirmed to be key odorants, including 1-octen-3-ol, hexanal, nonanal, phenylacetaldehyde, linalool, 4-oxoisophorone, theaspirane, methyl salicylate, etc. Among the studies above, 42 out of 78 volatiles and 14 out of 34 odorants were identified in DFF for the first time. Then, the aroma profile of the DFF was simulated successfully by aroma recombination experiments based on the quantitation results, and the omission test suggested that alcohols are the decisive type of compounds in the DFF key odorants. In addition, a progressive addition test showed that the aroma recombinate prepared with 18 reference key odorants was able to reconstruct the characteristic aroma of DFF. In comparison, the recombinate constituted by mixing all 34 reference odorants in the same concentrations as determined in the DDF sample could mimic the flower scent and closely match the sensory attributes of the original D. officinale fresh flower.


Assuntos
Dendrobium , Perfumes , Compostos Orgânicos Voláteis , Flores/química , Odorantes/análise , Olfatometria , Compostos Orgânicos Voláteis/análise
9.
World J Gastrointest Oncol ; 13(11): 1709-1724, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34853645

RESUMO

BACKGROUND: Pancreatic cancer (PC) is one of the most lethal malignancies worldwide. It is known that the proliferation of PC cells is a critical process in the disease. Previous studies have failed to identify the key genes associated with PC cell proliferation, using bioinformatic analysis, genome-wide association studies, and candidate gene testing. AIM: To investigate the function of the chromobox 8 (CBX8)/receptor substrate 1 (IRS1)/AKT axis in PC. METHODS: A genome-wide CRISPR-Cas9 screening was performed to select genes that could facilitate PC cell proliferation. Quantitative reverse transcription-polymerase chain reaction was used to detect the expression of CBX8 in PC tissues and cells. The regulatory roles of CBX8 in cell proliferation, migration, and invasion were verified by in vivo and in vitro functional assays. RESULTS: CBX8 was upregulated in PC tissues and shown to drive PC cell proliferation. Higher expression of CBX8 was correlated with worse outcomes of PC patients from two independent cohorts comprising a total of 116 cases. CBX8 was also proved to serve as a promising therapeutic target for a PC xenograft model. We demonstrated that hypoxia-inducible factor (HIF)-1a induced CBX8 transcription by binding to the promoter of CBX8. CBX8 efficiently activated the PI3K/AKT signaling by upregulating insulin IRS1. CONCLUSION: CBX8 is a key gene regulated by HIF-1α, and activates the IRS1/AKT pathway, which suggests that targeting CBX8 may be a promising therapeutic strategy for PC.

10.
Front Immunol ; 12: 688910, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34177945

RESUMO

Lactate is an end product of glycolysis. As a critical energy source for mitochondrial respiration, lactate also acts as a precursor of gluconeogenesis and a signaling molecule. We briefly summarize emerging concepts regarding lactate metabolism, such as the lactate shuttle, lactate homeostasis, and lactate-microenvironment interaction. Accumulating evidence indicates that lactate-mediated reprogramming of immune cells and enhancement of cellular plasticity contribute to establishing disease-specific immunity status. However, the mechanisms by which changes in lactate states influence the establishment of diverse functional adaptive states are largely uncharacterized. Posttranslational histone modifications create a code that functions as a key sensor of metabolism and are responsible for transducing metabolic changes into stable gene expression patterns. In this review, we describe the recent advances in a novel lactate-induced histone modification, histone lysine lactylation. These observations support the idea that epigenetic reprogramming-linked lactate input is related to disease state outputs, such as cancer progression and drug resistance.


Assuntos
Ácido Láctico/metabolismo , Acetilcoenzima A/metabolismo , Animais , Epigênese Genética , Histonas/metabolismo , Humanos , Ácido Láctico/imunologia , Microambiente Tumoral
11.
Zhongguo Zhong Yao Za Zhi ; 45(12): 2784-2791, 2020 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-32627451

RESUMO

Jiaotai Pills is a traditional medical prescription to treat the incompatibility of heart and kidney. It has the distinctive functions of heart and kidney communication, sedation and hypnosis, anti-anxiety and depression, as well as the improvement of insulin resistance. However, this pill is broadly used to cure insomnia, anxiety, depression, and diabetes in the contemporary clinical trials. Based on the article, it illustrates the research progress of the chemical ingredients, pharmacological actions, and clinical applications of Jiaotai Pills. With respect to the "five principles" of Q-marker in Chinese medicine, the Q-marker of Jiaotai Pills is comprehensively predicted and analyzed, noting that berberine, epiberberine, coptisine chloride, palmatine chloride, berberine chloride, berberrubine chloride, ferulic acid, cinnamic acid, cinnamaldehyde, proanthocyanidin B2 can be treated as the Q-marker of Jiaotai Pills. In addition, these components of Q-marker have been selected as indicators to provide a significant reference for the quality control and surveillance research of Jiaotai Pills.


Assuntos
Medicamentos de Ervas Chinesas , Biomarcadores , Controle de Qualidade
12.
World J Gastroenterol ; 26(19): 2349-2373, 2020 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-32476798

RESUMO

BACKGROUND: Pancreatic cancer (PC) is one of the deadliest cancers worldwide. PC metastasis involves a complex set of events, including epithelial-mesenchymal transition (EMT), that increase tumor cell invasiveness. Recent evidence has shown that hypoxia is a major EMT regulator in pancreatic cancer cells and facilitates metastasis; however, the mechanisms remain elusive. AIM: To investigate the role of miR-301a in hypoxia-induced EMT in PC cells. METHODS: Real-time PCR and Western blot analysis were used to detect the expression of miR-301a and EMT markers in PDAC cells cultured in hypoxic and normoxic conditions. Western blot analysis was used to detect the expression of EMT markers in PDAC cells with miR-301a overexpression. Wound healing assay and Transwell assay were used to detect the migration capabilities of PDAC cells with miR-301a overexpression and knockout. Luciferase assay was used to detect the miR-301a promoter and the 3' untranslated region activity of TP63. Orthotopic PC mouse models were used to study the role of miR-301a in metastasis of PDAC cells in vivo. In situ hybridization assay was used to detect the expression of miR-301a in PDAC patient samples (adjacent paratumor and paired tumor tissues). . RESULTS: Hypoxic environment could directly promote the EMT of PC cells. The expression level of miR-301a was increased in a HIF2α dependent manner in hypoxia-cultured CFPAC-1 and BxPC-3 cells. Overexpression of miR-301a enhanced the hypoxia-induced EMT of PC cells, while knocking out miR-301a result in the suppression of hypoxia-induced EMT. TP63 was a direct target of miR-301a and involved in the metastatic process of PC cells. Furthermore, miR-301a upregulation facilitated PDAC distant metastasis and lymph node metastasis in vivo. Additionally, miR-301a overexpression was indicative of aggressive clinicopathological behaviors and poor prognosis. CONCLUSION: The newly identified HIF-2α-miR301a-TP63 signaling pathway may play a crucial role in hypoxia-induced EMT in PDAC cells.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Carcinoma Ductal Pancreático/genética , MicroRNAs/genética , Neoplasias Pancreáticas/genética , Fatores de Transcrição/genética , Proteínas Supressoras de Tumor/genética , Regiões 3' não Traduzidas/genética , Animais , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/patologia , Hipóxia Celular/genética , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Inativação de Genes , Humanos , Estimativa de Kaplan-Meier , Masculino , Camundongos , MicroRNAs/análise , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Pâncreas/patologia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Prognóstico , Regiões Promotoras Genéticas/genética , Transdução de Sinais/genética , Ensaios Antitumorais Modelo de Xenoenxerto
13.
Zhongguo Zhong Yao Za Zhi ; 45(2): 383-390, 2020 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-32237322

RESUMO

Enzyme-linked immunosorbent assay(ELISA) and metabolomics were used to analyze and compare two animal models of heart-kidney insomnia, in order to explore a more ideal animal model and preliminarily explore the essence of heart-kidney insomnia. Based on the clinical symptoms and disease characteristics of heart-kidney insomnia, the animal model of heart-kidney insomnia was reproduced through intraperitoneal injection with p-chlorophenylalanine(PCPA) and multi-factor interaction. The animal model of disease-syndrome combination was evaluated by behavioral observation, ELISA and metabolomics. Wistar rats were randomly divided into normal group, PCPA group and compound model group(FH). The rats' behavior, body weight, adrenal index and spleen index were recorded. The levels of corticotropin releasing hormone(CRH) and adrenocorticotropin(ACTH) in serum were detected by ELISA, and the differential metabolites in serum were detected by UPLC-QE-MS. The body weight and adrenal index in FH group were significantly lower than those in PCPA group(P<0.05); whereas ACTH and CRH in FH group were significantly higher than those in PCPA group by ELISA; nine potential biomarkers were identified by serum sample statistics. There were four main metabolic pathways in cardiorenal insomnia: pentose phosphate metabolism, alanine, aspartic acid and glutamic acid metabolism, histidine metabolism, and taurine and subtaurine metabolism. PCPA and multi-factor interaction method can successfully replicate the insomnia model, but multi-factor modeling method is more similar to clinical traditional Chinese medicine syndrome. Animal behavior, ELISA and metabolomics were used to evaluate the rat model of cardiorenal insomnia from in vitro to in vivo, from macro to micro, and from individual to the whole.


Assuntos
Modelos Animais de Doenças , Metaboloma , Soro/metabolismo , Distúrbios do Início e da Manutenção do Sono/metabolismo , Animais , Medicina Tradicional Chinesa , Ratos , Ratos Wistar
14.
Neurosci Bull ; 36(2): 153-164, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31444653

RESUMO

Fear memories are critical for survival. Nevertheless, over-generalization of these memories, depicted by a failure to distinguish threats from safe stimuli, is typical in stress-related disorders. Previous studies have supported a protective role of ketamine against stress-induced depressive behavior. However, the effect of ketamine on fear generalization remains unclear. In this study, we investigated the effects of ketamine on fear generalization in a fear-generalized mouse model. The mice were given a single sub-anesthetic dose of ketamine (30 mg/kg, i.p.) 1 h before, 1 week before, immediately after, or 22 h after fear conditioning. The behavioral measure of fear (indicated by freezing level) and synaptic protein expression in the basolateral amygdala (BLA) and inferior-limbic pre-frontal cortex (IL-PFC) of mice were examined. We found that only ketamine administered 22 h after fear conditioning significantly decreased the fear generalization, and the effect was dose-dependent and lasted for at least 2 weeks. The fear-generalized mice showed a lower level of brain-derived neurotrophic factor (BDNF) and a higher level of GluN2B protein in the BLA and IL-PFC, and this was reversed by a single administration of ketamine. Moreover, the GluN2B antagonist ifenprodil decreased the fear generalization when infused into the IL-PFC, but had no effect when infused into the BLA. Infusion of ANA-12 (an antagonist of the BDNF receptor TrkB) into the BLA or IL-PFC blocked the effect of ketamine on fear generalization. These findings support the conclusion that a single dose of ketamine administered 22 h after fear conditioning alleviates the fear memory generalization in mice and the GluN2B-related BDNF signaling pathway plays an important role in the alleviation of fear generalization.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/metabolismo , Condicionamento Clássico/efeitos dos fármacos , Medo/efeitos dos fármacos , Ketamina/farmacologia , Receptores de N-Metil-D-Aspartato/metabolismo , Tonsila do Cerebelo/metabolismo , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Córtex Pré-Frontal/metabolismo , Transdução de Sinais/efeitos dos fármacos
15.
J Craniofac Surg ; 30(5): 1601-1604, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31299778

RESUMO

Facial anthropometric measurements play an important part not only in forensic cases but also in clinical treatments. The utilization of 2D photograph methods in facial anthropometric studies to found database with age, gender, ethnicity, and region was expanded by other races but little for Han nationality. This study was undertaken to describe reference ranges of facial anthropometric proportions of Han nationality and compare the anthropometric characteristics with other ethnicities. Our subjects focused on full-face photos of Han nationality in South China which consisted of 1176 healthy person (425 adult males, 421 adult females and 157 underage boys and 173 underage girls). Eight anthropometric landmarks on photos were examined by ImageJ software, and 7 anthropometric ratios were analyzed. The results indicated sex- and age- and ethnics-related anthropometric variations in Chinese Han nationality in South China. For adults, females have larger ratios in intercanthal-nasal width and lip height index and smaller nose width index; for impubes, boys were larger in lip height index and smaller in lip width ratios than girls, but as age achieved, the underage boys and girls exhibited a significantly larger nose width index and lip width index, smaller canthal index, intercanthal-nasal width and lip height index. Comparing with Japanese, India, North American and Persian, Chinese Han showed great difference in facial anthropometric proportions.


Assuntos
Antropometria , Antropometria/métodos , Povo Asiático , China/etnologia , Pálpebras/anatomia & histologia , Face/anatomia & histologia , Feminino , Humanos , Índia , Masculino , Valores de Referência
16.
Huan Jing Ke Xue ; 40(2): 987-993, 2019 Feb 08.
Artigo em Chinês | MEDLINE | ID: mdl-30628368

RESUMO

The effects of biochar addition to compost on change characteristics and passivation effect of heavy metals (Cd, Pb, Cu, Zn, Ni) were investigated during the process of sludge composting with two different composts (group A:with biochar; group B:without biochar) and land application of compost. The results indicated that the total amount of heavy metals (except Ni) did not change significantly during the process of sludge composting and land application of compost. Additionally, biochar addition had little effect on the total amount of heavy metals. During the sludge composting process, five heavy metals (Cd, Pb, Cu, Zn, Ni) were passivated. Sludge composting with the addition of biochar can decrease the available contents of heavy metals, and the passivation effect of heavy metals was significant (P<0.05). The passivation rate of the five examined heavy metals (Cd, Pb, Cu, Zn, Ni)ranged from 16.39%-43.10%, and the passivation effect for Zn and Ni was more significant. However, the passivation effect was not significant in the sludge composting process without the addition of biochar (P>0.05). The concentrations of heavy metals in soil increased with the application of sewage sludge compost products. In the short term, biochar had a certain passivation effect on the available heavy metals in soils with sludge compost application, but the effect was not significant.


Assuntos
Carvão Vegetal , Compostagem , Metais Pesados/análise , Esgotos , Solo/química
17.
Chin J Nat Med ; 16(2): 113-124, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29455726

RESUMO

Due to ineffectiveness and side effects of existing analgesics, chronic pain has become one of the most complex and difficult problems in the clinic. Monoacylglycerol lipase (MAGL) is an essential hydrolase in the endocannabinoid system and has been identified as a potential target for the treatment of pain. In the present study, we designed and synthesized twelve tanshinone IIA analogs and screened their activity against MAGL. Selected compounds were tested for analgesic activity in vivo, with the acetic acid writhing test model. Among the test compounds, compound III-3 (IC50 120 nmol·L-1) showed significant activity against MAGL and ameliorated the clinical progression in the mouse pain model. Additionally, compound III-3, substitution with N-methyl-2-morpholinoacetamide, demonstrated improved solubility relative to tanshinone IIA.


Assuntos
Abietanos/administração & dosagem , Abietanos/síntese química , Analgésicos/administração & dosagem , Analgésicos/síntese química , Dor Crônica/tratamento farmacológico , Abietanos/química , Analgésicos/química , Animais , Dor Crônica/enzimologia , Avaliação Pré-Clínica de Medicamentos , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Monoacilglicerol Lipases/antagonistas & inibidores , Monoacilglicerol Lipases/metabolismo , Relação Estrutura-Atividade
18.
Hum Gene Ther ; 29(2): 223-233, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29338433

RESUMO

Clustered regularly interspaced short palindromic repeats (CRISPR)-caspase 9 (Cas9) genome editing technology holds great promise for the field of human gene therapy. However, a lack of safe and effective delivery systems restricts its biomedical application. Here, a folate receptor-targeted liposome (F-LP) was used to deliver CRISPR plasmid DNA co-expressing Cas9 and single-guide RNA targeting the ovarian cancer-related DNA methyltransferase 1 (DNMT1) gene (gDNMT1). F-LP efficiently bound the gDNMT1 plasmid and formed a stable complex (F-LP/gDNMT1) that was safe for injection. F-LP/gDNMT1 effectively mutated endogenous DNMT1 in vitro, and then expressed the Cas9 endonuclease and downregulated DNMT1 in vivo. The tumor growth of both paclitaxel-sensitive and -resistant ovarian cancers were inhibited by F-LP/gDNMT1, which shows fewer adverse effects than paclitaxel injection. Therefore, CRISPR-Cas9-targeted DNMT1 manipulation may be a potential therapeutic regimen for ovarian cancer, and lipid-mediated delivery systems represent promising delivery vectors of CRISPR-Cas9 technology for precise genome editing therapeutics.


Assuntos
DNA (Citosina-5-)-Metiltransferase 1/genética , Técnicas de Transferência de Genes , Terapia Genética , Neoplasias Ovarianas/genética , Sistemas CRISPR-Cas/genética , Proliferação de Células/efeitos dos fármacos , DNA (Citosina-5-)-Metiltransferase 1/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Receptor 1 de Folato/genética , Receptor 1 de Folato/uso terapêutico , Edição de Genes , Regulação Neoplásica da Expressão Gênica , Humanos , Lipossomos/administração & dosagem , Lipossomos/química , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos
19.
Huan Jing Ke Xue ; 38(1): 405-411, 2017 Jan 08.
Artigo em Chinês | MEDLINE | ID: mdl-29965073

RESUMO

Two different sludge composting products (with and without biochar) were applied in field to study the variations of total mercury (THg) and methylmercury (MeHg) in soil and plants,as well as their migration in the soil-plant system and accumulation ability in plants during the sludge compost land use process.The results indicated that the concentrations THg and MeHg in soil increased after applying sewage sludge compost products,while the THg level was still lower than the secondary standard of national soil environmental quality.Biochar was speculated to probably promote the soil mercury methylation with lower MeHg/THg ratios in different soil treatments.THg concentrations in mature plants were significantly lower than those in seedling stage,but MeHg levels were higher than those in seedling stage.An obvious influence of composting on MeHg enrichment in plants was observed,and this similar effect was not found for THg enrichment.MeHg concentration in the soils applied with biochar compost was significantly higher than that without applying biochar compost soil,while MeHg in plant presented a contrary trend with higher level observed in no-biochar compost soil,suggesting that the addition of biochar could be in favour of soil MeHg formation and inhibit the MeHg accumulation in plants by influencing its migration.Since a strong MeHg accumulation ability with BCF of 1.24-14.63 was present in plant,the mercury ecological risk in soil environment caused by long-term fertilizing should be noticed.


Assuntos
Mercúrio/análise , Compostos de Metilmercúrio/análise , Plantas/química , Esgotos/química , Poluentes do Solo/análise , Compostagem , Monitoramento Ambiental , Solo
20.
Huan Jing Ke Xue ; 38(4): 1647-1653, 2017 Apr 08.
Artigo em Chinês | MEDLINE | ID: mdl-29965170

RESUMO

Effect of application of sewage sludge compost on the emission of greenhouse gas from soil was investigated by analyzing the dynamic characteristics and emission factor of CO2, CH4 and N2O in soil after spiking two different composts (A:compost with biochar, B:compost without biochar) with varying fertilizing amount into soil. The results indicated that emissions of CO2 and CH4 mainly occurred in the plant growth period with low fertilizer amount of biomass charcoal compost reducing CO2 emissions, and high application content increasing CO2 emissions. CH4 emission fluxes showed negative values, indicating that soil could adsorb CH4, and the adsorbing amount for control was significantly higher than those for other treatments (P<0.01). The absorbing amount in treatment A increased with the fertilizing amount (P<0.05). N2O emissions mainly occurred at the germination and seedling stages, and emission fluxes increased with the fertilizing amount (P<0.01). N2O was considered as the main generated greenhouse gas during agricultural process with sludge compost, and its emission factor from sludge compost soil was 1.02%-1.90% (A compost) and 1.28%-2.93% (B compost), respectively. Biochar could significantly reduce the carbon emission, as the total greenhouse gas released from soil with biochar compost was 19.49% to 35.56% less than that in soil without biochar, which was more obvious for N2O emission reduction (compared with CH4 mitigation).


Assuntos
Compostagem , Gases de Efeito Estufa/análise , Esgotos/química , Solo/química , Dióxido de Carbono/análise , Metano/análise , Óxido Nitroso/análise
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