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1.
Mar Pollut Bull ; 158: 111418, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32753202

RESUMO

In this study, the recent history of heavy metal pollution in the Fangcheng Bay (South China) was reconstructed utilizing three 210Pb-dated sediment cores. The metal concentration profiles display three trends since the 1970s and clearly reflect local urbanization and industrialization. The metals in the Fangcheng Bay started to accumulate in the 1970s but remained relatively low until the 1990s which corresponds to the slow urbanization and industrialization. The metal accumulation in the eastern Fangcheng Bay peaked in the early 2000s following the steep increases in accordance with the rapid industrialization of the eastern Fangcheng Bay where the core HSL was collected. Conversely, the heavy metal profiles in the western Fangcheng Bay present slight step increases in the early 2000s followed by a dramatic metal enrichment in the late 2000s; the expansion of these two cores, which begins in the early 2000s, concurs well with the rapid local urbanization and industrialization.


Assuntos
Metais Pesados/análise , Poluentes Químicos da Água/análise , Baías , China , Monitoramento Ambiental , Sedimentos Geológicos , Desenvolvimento Industrial , Urbanização
2.
Arthritis Rheumatol ; 2020 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-32602200

RESUMO

OBJECTIVES: Coagulopathy is one of the characteristics of critically ill patients with Coronavirus Disease 2019 (COVID-19). Antiphospholipid antibodies (aPLs) contribute to coagulopathy, but their role in COVID-19 remains unclear. We aimed to determine the prevalence and characteristics of aPLs in patients with COVID-19. METHODS: Sera collected from 66 critically ill and 13 non-critically ill patients with COVID-19 were tested for anti-cardiolipin (aCL) and anti-ß2-glycoprotein 1 (aß2GP1) (IgG, IgM, and IgA) and IgG aß2GP1-D1 by the chemiluminescence assay (CIA) and IgM and IgG anti-phosphatidylserine/prothrombin (aPS/PT) by ELISA. RESULTS: aPLs were detected in 47.0% of critically ill patients (31/66), but not in patients with non-critical conditions. IgA aß2GP1 was the most common aPL, present in 28.8% (19/66) critically ill patients, followed by IgA aCL (25.8%,17/66) and IgG aß2GP1 (18.2%,12/66). For multiple aPLs, IgA aß2GP1+IgA aCL was the most common type (22.7%, 15/66), followed by IgA aß2GP1+IgA aCL+ IgG aß2GP1 (15.2%, 10/66). aPLs emerge around 35-39 days post-disease onset. Dynamic analysis of aPLs revealed 4 patterns based on persistence or transient appearance of the aPLs. Patients with multiple aPLs displayed significantly higher incidence of cerebral infarction (p=0.023). CONCLUSIONS: aPLs were common in critically ill patients. Multiple medium or high levels aPLs may help identify patients at risk of developing cerebral infarction. aPLs may be transient and disappear within a few weeks, but in genetically predisposed patients, COVID-19 may trigger the development of "COVID-19-induced-APS-like-syndrome". Long-term follow-up on COVID-19 patients positive for aPLs would be of great importance.

3.
ACS Synth Biol ; 2020 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-32610012

RESUMO

Acetogenic bacteria are rising in popularity as chassis microbes for biotechnology due to their capability of converting inorganic one-carbon (C1) gases to organic chemicals. To fully uncover the potential of acetogenic bacteria, synthetic biology tools are imperative to either engineer designed functions or to interrogate the physiology. Here, we report a genome-editing tool at a one-nucleotide resolution, namely base editing, for acetogenic bacteria based on CRISPR-targeted deamination. This tool combines nuclease deactivated Cas9 with activation-induced cytidine deaminase to enable cytosine-to-thymine substitution without DNA cleavage, homology-directed repair, and donor DNA, which are generally the bottlenecks for applying conventional CRISPR-Cas systems in bacteria. We designed and validated a modularized base-editing tool in the model acetogenic bacterium Clostridium ljungdahlii. The editing principles were investigated, and an in-silico analysis revealed the capability of base editing across the genome and the potential for off-target events. Moreover, genes related to acetate and ethanol production were disrupted individually by installing premature STOP codons to reprogram carbon flux toward improved acetate production. This resulted in engineered C. ljungdahlii strains with the desired phenotypes and stable genotypes. Our base-editing tool promotes the application and research in acetogenic bacteria and provides a blueprint to upgrade CRISPR-Cas-based genome editing in bacteria in general.

4.
Artigo em Inglês | MEDLINE | ID: mdl-32633586

RESUMO

PURPOSE: To evaluate the accuracy of the robot-assisted computed tomography (CT)-guided coordinate positioning puncture method by phantom and animal experiments. MATERIAL AND METHODS: In the phantom experiment, seven robot-assisted punctures were made to evaluate the accuracy of the method. In the animal experiment, 18 punctures (nine robotic and nine manual) were made in the livers of nine rabbits. The indicators, such as needle-tract length, angle deviation, puncture accuracy, number of scans required, and radiation exposure dose were compared between manual and robotic punctures. The paired-samples t-test was used for analysis. RESULTS: In the phantom experiment, the mean accuracy of seven punctures was 2.67 mm. In the animal experiment, there was no significant difference in needle-tract length (32.58 mm vs. 34.04 mm, p = .606), angle deviation (17.21° vs. 21.23° p = .557) and puncture accuracy (8.42 vs. 8.77 mm, p = .851) between the two groups. However, the number CT scans required (2.44 vs. 3.33, p = .002), and the radiation exposure dose (772.98 vs. 1077.89 mGy/cm, p = .003) were lower in the robot group than in the manual group. CONCLUSIONS: The coordinate positioning puncture method under robot-assisted CT-guidance can reach an accuracy that is comparable to that of the traditional manual CT-guided puncture method and with fewer CT scanning times accompanied with a lower radiation dosage.

5.
Zhongguo Zhong Yao Za Zhi ; 45(12): 2765-2771, 2020 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-32627449

RESUMO

Suanzaoren Decoction is a classic prescription for nourishing the heart and liver, nourishing blood and tranquilizing the mind. It has the functions of sedation and hypnosis, anti-anxiety, anti-depression, anti-convulsion and so on. Modern clinic is mostly used to treat different types of insomnia, depression, neurasthenia, tension headache and vertigo. In this paper, the chemical consti-tuents, pharmacological effects and clinical application of Suanzaoren Decoction are reviewed. Based on this, the quality marker(Q-marker) of Suanzaoren Decoction was predicted and analyzed according to the "five principles" of Q-marker of traditional Chinese medicine--transmission and traceability, specificity, effectiveness, measurability and compatibility environment of compound prescriptions. The results indicated that jujuboside, spinosin, ferulic acid, senkyunolide Ⅰ, sarsasapogenin, mangiferin, liquiritoside and glycyrrhizic acid were predicted and analyzed, and those can be used as Q-markers of Suanzaoren Decoction. Subsequently, the above components can be selected as indicators to control and evaluate the quality of Suanzaoren Decoction and its preparations, and establish a quality traceability system.

6.
Nat Commun ; 11(1): 3410, 2020 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-32641700

RESUMO

COVID-19 is associated with 5.1% mortality. Although the virological, epidemiological, clinical, and management outcome features of COVID-19 patients have been defined rapidly, the inflammatory and immune profiles require definition as they influence pathogenesis and clinical expression of COVID-19. Here we show lymphopenia, selective loss of CD4+ T cells, CD8+ T cells and NK cells, excessive T-cell activation and high expression of T-cell inhibitory molecules are more prominent in severe cases than in those with mild disease. CD8+ T cells in patients with severe disease express high levels of cytotoxic molecules. Histochemical studies of lung tissue from one fatality show sub-anatomical distributions of SARS-CoV-2 RNA and massive infiltration of T cells and macrophages. Thus, aberrant activation and dysregulation of CD8+ T cells occur in patients with severe COVID-19 disease, an effect that might be for pathogenesis of SARS-CoV-2 infection and indicate that immune-based targets for therapeutic interventions constitute a promising treatment for severe COVID-19 patients.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/patologia , Pneumonia Viral/imunologia , Pneumonia Viral/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus/imunologia , Biomarcadores/metabolismo , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/patologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/patologia , Quimiotaxia de Leucócito , China/epidemiologia , Infecções por Coronavirus/sangue , Infecções por Coronavirus/virologia , Citocinas/sangue , Feminino , Humanos , Inflamação , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/patologia , Contagem de Leucócitos , Pulmão/imunologia , Pulmão/virologia , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/virologia
7.
Opt Express ; 28(14): 19988-19996, 2020 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-32680067

RESUMO

Random phase-shifting digital holography based on a self-calibrated system is proposed. In the proposed method, the hologram and the calibration interference fringes can be recorded simultaneously in a single image based on the space-division-multiplexing technique. Three randomly phase-shifted holograms and corresponding interference fringes are recorded, and the phase-shifting amount between each two adjacent holograms is calculated by the sampling Moiré method from the calibration interference fringes. A reflective object is used to demonstrate the effectiveness of the proposed method in the numerical and experiment.

8.
Cell Metab ; 32(2): 188-202.e5, 2020 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-32610096

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic presents an unprecedented threat to global public health. Herein, we utilized a combination of targeted and untargeted tandem mass spectrometry to analyze the plasma lipidome and metabolome in mild, moderate, and severe COVID-19 patients and healthy controls. A panel of 10 plasma metabolites effectively distinguished COVID-19 patients from healthy controls (AUC = 0.975). Plasma lipidome of COVID-19 resembled that of monosialodihexosyl ganglioside (GM3)-enriched exosomes, with enhanced levels of sphingomyelins (SMs) and GM3s, and reduced diacylglycerols (DAGs). Systems evaluation of metabolic dysregulation in COVID-19 was performed using multiscale embedded differential correlation network analyses. Using exosomes isolated from the same cohort, we demonstrated that exosomes of COVID-19 patients with elevating disease severity were increasingly enriched in GM3s. Our work suggests that GM3-enriched exosomes may partake in pathological processes related to COVID-19 pathogenesis and presents the largest repository on the plasma lipidome and metabolome distinct to COVID-19.

9.
Kidney Blood Press Res ; 45(4): 623-630, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32492687

RESUMO

INTRODUCTION: Thrombocytopenia, ascites, myelofibrosis, renal dysfunction, and organomegaly (TAFRO) syndrome is a newly recognized and rare clinical subtype of Castleman disease. Renal involvement in TAFRO syndrome usually presents with mild proteinuria, microscopic hematuria, and acute renal injury requiring temporary renal replacement. There is no standard therapy available and treatment failures are common, leading to a poor prognosis. We report a case of acute renal failure caused by TAFRO syndrome, successfully managed by long-term corticosteroids combined with bortezomib and cyclophosphamide. CASE PRESENTATION: The patient was a 52-year-old female who presented with fever, anasarca, oliguria, and abdominal distension at first. She progressed rapidly to anuric renal failure requiring hemodialysis. She also demonstrated thrombocytopenia, anemia, coagulopathy, and a hyperinflammatory status. Her CT scan showed severe polyserositis, splenomegaly, and lymphadenopathy. Her serum vascular epithelial growth factor level was significantly elevated. Axillary lymph node biopsy showed hyaline-vascular type Castleman disease, supporting the diagnosis of TAFRO syndrome. Her renal function recovered after high-dose steroids and supportive treatment. A weekly dosing regimen of bortezomib, cyclophosphamide, and dexamethasone combined with medium dose prednisone in between were deployed. Her blood cell count and renal function remained stable after 6 months. The inflammation was suppressed and the polyserositis resolved completely. CONCLUSION: TAFRO syndrome is rare and has a poor prognosis due to the lack of standard treatment. Our patient might be the first TAFRO case successfully treated by bortezomib, cyclophosphamide, and corticosteroids.

10.
Int J Neurosci ; : 1-6, 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32576077

RESUMO

Background: Contralateral C7 nerve transfer is a new surgical treatment for stroke patients with unilateral upper extremity paralysis, but neuropathic pain in the nonparalyzed side is the common complication after surgery. We report a stroke patient with neuropathic pain after C7 nerve transfer who received combination treatment of transcutaneous electrical nerve stimulation(TENS) and pregabalin.Case Summary: A 53-year old, 6 months post-stroke patient with right hemiplegia after contralateral C7 nerve transfer was admitted in our department with a significant neuropathic pain in his left upper extremity. The treatment of pregabalin and TENS were used for patient. The visual analogue scale(VAS), medical outcomes study sleep scale(MOS-SS) and hospital anxiety and depression scale(HADS) were assessed after 1 months treatment. After treatment, the pain of his nonparalyzed upper extremity was relieved, the sleeping quality and the anxiety and depression were improved in patient.Conclusion: This report suggests that the combination of pregabalin and TENS have prominent clinical effects on neuropathic pain of nonparalyzed side in stroke patients after contralateral C7 nerve transfer.

11.
Ren Fail ; 42(1): 483-488, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32438839

RESUMO

The coronavirus disease-19 (COVID-19) has spread over many countries and regions since the end of 2019, becoming the most severe public health event at present. Most of the critical cases developed multiple organ dysfunction, including acute kidney injury (AKI). Cytokine storm syndrome (CSS) may complicate the process of severe COVID-19 patients. This manuscript reviews the different aspects of blood purification in critically ill patients with AKI and increased inflammatory factors, and examines its potential role in severe COVID-19 treatment. Continuous renal replacement therapy (CRRT) has been practiced in many sepsis patients with AKI. Still, the timing and dosing need further robust evidence. In addition to the traditional CRRT, the high-throughput membrane with adsorption function and cytokine adsorption column are two representatives of recently emerging novel membrane technologies. Their potential in removing inflammatory factors and other toxins prospects for the treatment of severe COVID-19.


Assuntos
Betacoronavirus , Calcinose/terapia , Infecções por Coronavirus/terapia , Citocinas , Doenças das Valvas Cardíacas/terapia , Hipotricose/terapia , Pneumonia Viral/terapia , Terapia de Substituição Renal , Dermatopatias Genéticas/terapia , Calcinose/etiologia , Infecções por Coronavirus/complicações , Estado Terminal , Doenças das Valvas Cardíacas/etiologia , Humanos , Hipotricose/etiologia , Pandemias , Pneumonia Viral/complicações , Dermatopatias Genéticas/etiologia
12.
J Am Heart Assoc ; 9(10): e015743, 2020 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-32400247

RESUMO

Background The aim of this study was to identify associations between dietary intakes of eggs and cholesterol and all-cause and heart disease mortality in a US population. Methods and Results Data from the National Health and Nutrition Examination Survey 1999-2014 were used in this study, which included 37 121 participants ≥20 years of age. Dietary information was assessed via 24-hour dietary recalls at baseline. Mortality status was documented until December 31, 2015. Cox proportional hazards models were used to examine the associations between dietary intakes of eggs and cholesterol and all-cause and heart disease mortality. During a median follow-up of 7.8 years, 4991 deaths were documented, including 870 deaths from heart disease. No significant association was observed between additional daily consumption of half an egg and all-cause mortality (multivariable-adjusted hazard ratio, 1.04; 95% CI, 0.96-1.13), or heart disease mortality (0.96; 0.80-1.14). Each 50-mg/day increase of cholesterol intake was inversely associated with all-cause mortality among participants with daily intake <250 mg (0.87; 0.77-0.98), but positively associated with all-cause mortality among participants with daily intake ≥250 mg (1.07; 1.01-1.12). No significant association was found between dietary cholesterol intake and heart disease mortality. Conclusions No significant association was found between egg consumption and mortality in US adults. The association between dietary cholesterol intake and all-cause mortality depended on the baseline intake levels, with an inverse association in those with lower intake levels (<250 mg/day) but a positive association in those with higher intake levels (≥250 mg/day).

13.
BMC Cancer ; 20(1): 390, 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32375685

RESUMO

BACKGROUND: Osteosarcoma (OS) is the most frequent primary malignancy of bone with a high incidence in adolescence. This study aimed to construct a publicly available, integrated database of human OS, named HOsDb. METHODS: Microarray data, current databases, and a literature search of PubMed were used to extract information relevant to human OS-related genes and their transcription factors (TFs) and single nucleotide polymorphisms (SNPs), as well as methylation sites and microRNAs (miRNAs). This information was collated for constructing the HOsDb. RESULTS: In total, we identified 7191 OS tumor-related genes, 763 OS metastasis-related genes, and 1589 OS drug-related genes, corresponding to 190,362, 21,131, and 41,135 gene-TF pairs, respectively, 3,749,490, 358,361, and 767,674 gene-miRNA pairs, respectively; and 28,386, 2532, and 3943 SNPs, respectively. Additionally, 240 OS-related miRNAs, 1695 genes with copy number variations in OS, and 18 genes with methylation sites in OS were identified. These data were collated to construct the HOsDb, which is available at www.hosdatabase.com. Users can search OS-related molecules using this database. CONCLUSION: The HOsDb provides a platform that is comprehensive, quick, and easily accessible, and it will enrich our current knowledge of OS.

16.
J Org Chem ; 2020 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-32240591

RESUMO

A visible-light-induced, catalyst-free radical cross-coupling cyclization of diselenides or disulfides with N-allylbromodifluoroacetamide has been developed. This developed protocol exhibits good functional group tolerance and affords a variety of 4-thio- and 4-seleno-substituted 3,3-difluoro-γ-lactams in moderate to good yields. Based on control experiments, a plausible radical-radical cross-coupling pathway is proposed.

17.
Physiol Rep ; 8(6): e14405, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32212257

RESUMO

Protein kinase A (PKA) activity is pivotal for proper functioning of the human heart, and its dysregulation has been implicated in a variety of cardiac pathologies. PKA regulatory subunit 1α (R1α, encoded by the PRKAR1A gene) is highly expressed in the heart, and controls PKA kinase activity by sequestering PKA catalytic subunits. Patients with PRKAR1A mutations are often diagnosed with Carney complex (CNC) in early adulthood, and may die later in life from cardiac complications such as heart failure. However, it remains unknown whether PRKAR1A deficiency interferes with normal heart development. Here, we showed that left ventricular mass was reduced in young CNC patients with PRKAR1A mutations or deletions. Cardiac-specific heterozygous ablation of PRKAR1A in mice increased cardiac PKA activity, and reduced heart weight and cardiomyocyte size without altering contractile function at 3 months of age. Silencing of PRKAR1A, or stimulation with the PKA activator forskolin completely abolished α1-adrenergic receptor-mediated cardiomyocyte hypertrophy. Mechanistically, depletion of PRKAR1A provoked PKA-dependent inactivating phosphorylation of Drp1 at S637, leading to impaired mitochondrial fission. Pharmacologic inhibition of Drp1 with Mdivi 1 diminished hypertrophic growth of cardiomyocytes. In conclusion, PRKAR1A deficiency suppresses cardiomyocyte hypertrophy and impedes heart growth, likely through inhibiting Drp1-mediated mitochondrial fission. These findings provide a potential novel mechanism for the cardiac manifestations associated with CNC.

19.
J Biol Chem ; 295(13): 4265-4276, 2020 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-32075913

RESUMO

Recent clinical investigations indicate that anthracycline-based chemotherapies induce early decline in heart mass in cancer patients. Heart mass decline may be caused by a decrease in cardiac cell number because of increased cell death or by a reduction in cell size because of atrophy. We previously reported that an anthracycline, doxorubicin (DOX), induces apoptotic death of cardiomyocytes by activating cyclin-dependent kinase 2 (CDK2). However, the signaling pathway downstream of CDK2 remains to be characterized, and it is also unclear whether the same pathway mediates cardiac atrophy. Here we demonstrate that DOX exposure induces CDK2-dependent phosphorylation of the transcription factor forkhead box O1 (FOXO1) at Ser-249, leading to transcription of its proapoptotic target gene, Bcl-2-interacting mediator of cell death (Bim). In cultured cardiomyocytes, treatment with the FOXO1 inhibitor AS1842856 or transfection with FOXO1-specific siRNAs protected against DOX-induced apoptosis and mitochondrial damage. Oral administration of AS1842856 in mice abrogated apoptosis and prevented DOX-induced cardiac dysfunction. Intriguingly, pharmacological FOXO1 inhibition also attenuated DOX-induced cardiac atrophy, likely because of repression of muscle RING finger 1 (MuRF1), a proatrophic FOXO1 target gene. In conclusion, DOX exposure induces CDK2-dependent FOXO1 activation, resulting in cardiomyocyte apoptosis and atrophy. Our results identify FOXO1 as a promising drug target for managing DOX-induced cardiotoxicity. We propose that FOXO1 inhibitors may have potential as cardioprotective therapeutic agents during cancer chemotherapy.

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