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1.
Artigo em Inglês | MEDLINE | ID: mdl-33035161

RESUMO

This paper presents a pulse-stimulus sensor readout circuit for use in cardiovascular disease examinations. The sensor is based on a gold nanoparticle plate with an antibody post-modification. The proposed system utilizes gated pulses to detect the biomarker Cardiac Troponin I in an ionic solution. The characteristic of the electrostatic double-layer capacitor generated by the analyte is related to the concentration of Cardiac Troponin I in the solvent. After sensing by the transistor, a current-to-frequency converter (I-to-F) and delay-line-based time-to-digital converter (TDC) convert the information into a series of digital codes for further analysis. The design is fabricated in a 0.18-um standard CMOS process. The chip occupies an area of 0.92 mm2 and consumes 125 uW. In the measurements, the proposed circuit achieved a 1.77 Hz/pg-mL sensitivity and 72.4 dB dynamic range.

2.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1605-1610, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067961

RESUMO

OBJECTIVE: To investigate the effect and possible mechanism of up-regulation of p-Akt by doxycycline (DOX) on myeloma cell line H929. METHODS: Multiple myeloma cell line H929 was treated with DOX at different concentrations for different times, and cell proliferation rate was measured by CCK-8 assay. The protein expression level of p-Akt, PTEN, p-PDK1, p-mTOR, p-GSK-3ß, and p-BAD was analyzed by Western blot. The mRNA levels of mTOR, BCL-2, and NF-κB was analyzed by RT-PCR. PI3K inhibitor Wortmannin was used to antagonize the up-regulation of p-Akt, and the cell proliferation and p-Akt protein expression level were analyzed by CCK-8 assay and Western blot respectively. RESULTS: DOX could inhibit the proliferation of H929 cells and up-regulate the expression of p-Akt at the same time. The protein levels of both p-PDK1 and PTEN in H929 cells did not alter significantly during DOX treatment. The expressions of p-BAD and p-GSK-3ß were up-regulated in H929 cells after treated with DOX, but the expression of p-mTOR was not altered. The mRNA levels of mTOR, BCL-2, and NF-κB in H929 were all down-regulated in H929 cells during DOX treatment. The effect up-regulating p-Akt level by DOX was suppressed when DOX combined with PI3K inhibitor Wortmannin and Wortmannin could enhance the inhibitory effect of DOX in H929 cells. CONCLUSION: DOX can activate PI3K/Akt signaling pathway in H929 cells, and antagonizing this effect of DOX may enhance its cytotoxicity to myeloma cells.

3.
J Immunol ; 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33046503

RESUMO

Emerging evidence indicates that Myo9b is a cancer metastasis-related protein and functions in a variety of immune-related diseases. However, it is not clear whether and how Myo9b functions in malignant pleural effusion (MPE). In this study, our data showed that Myo9b expression levels correlated with lung cancer pleural metastasis, and nucleated cells in MPE from either patients or mice expressed a lower level of Myo9b than those in the corresponding blood. Myo9b deficiency in cancer cells suppressed MPE development via inhibition of migration. Myo9b deficiency in mice suppressed MPE development by decreasing TH1 cells and increasing TH17 cells. CD4+ naive T cells isolated from Myo9b-/- mouse spleens exhibited less TH1 cell differentiation and more TH17 cell differentiation in vitro. mRNA sequencing of nucleated cells showed that T cell-specific adaptor protein (TSAd) was downregulated in Myo9b-/- mouse MPE, and enrichment of the H3K27me3 mark in the TSAd promoter region was found in the Myo9b-/- group. Naive T cells purified from wild type mouse spleens transfected with TSAd-specific small interfering RNAs (siRNAs) also showed less TH1 cell differentiation and more TH17 cell differentiation than those from the siRNA control group. Furthermore, downregulation of TSAd in mice using cholesterol-conjugated TSAd-specific siRNA suppressed MPE development, decreased TH1 cells, and increased TH17 cells in MPE in vivo. Taken together, Myo9b deficiency suppresses MPE development not only by suppressing pleural cancer metastasis but also by regulating TH1/TH17 cell response via a TSAd-dependent pathway. This work suggests Myo9b and TSAd as novel candidates for future basic and clinical investigations of cancer.

4.
Int J Artif Organs ; : 391398820962112, 2020 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-33016167

RESUMO

OBJECTIVES: Examine the impacts of age, diabetes, gender, and access type on vascular access (VA) associated costs among Chinese hemodialysis (HD) patients. METHODS: We retrospectively included patients whose first permanent VA was created at the West China Hospital. Clinical characteristics, maturation, intervention, utilization, and exchange of every VA, as well as VA-related infection were collected. The study period for each patient was from HD initiation to the last follow-up. VA-related costs, including those for placement and intervention procedures, were calculated according to the standards set in 2019 for Chinese tertiary hospitals. Mann-Whitney U and Chi-square tests were conducted for comparisons between groups. RESULTS: A total of 358 Chinese HD patients experienced functionally 143 arteriovenous fistula (AVF), 22 arteriovenous graft (AVG), and 439 tunneled cuffed central venous catheter (tcCVC) during a median study period of 26 (IQR 13-44) months, of which 42.5% used more than one permanent VA. The median annual VA-related cost in the groups of age >75 years and ⩽75 years, diabetes and non-diabetes, male and female, was $525 and $397 (p = 0.016), $459 and $462 (p = 0.64), $476 and $445 (p = 0.94), respectively. The median monthly costs for AVF ($18), AVG ($289), and tcCVC ($37) were significantly different. CONCLUSION: HD patients aged >75 years had significantly higher annual VA-related costs. However, the annual VA-related costs did not differ across the diabetes groups or the gender groups. AVF was the most cost-effective permanent VA type in China, partly due to the inexpensive materials used compared to AVG or tcCVC.

5.
Biomark Med ; 14(13): 1229-1242, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33021390

RESUMO

Aim: To develop robust and accurate prognostic biomarkers to help clinicians optimize therapeutic strategies. Materials & methods: Differentially prognosis-related autophagy genes were identified by bioinformatics analysis method. Results: Seven prognosis-related autophagy genes were more significantly related to the prognosis of hepatocellular carcinoma (HCC). Functional enrichment analysis demonstrated that these genes were mainly enriched in the autophagy pathway. BIRC5, HSPB8 and TMEM74 exhibited significant prognostic value for HCC. Besides, the risk score and BIRC5 have significant significance with clinicopathological significance of HCC. Conclusion: The research has identified a number of prognosis-related autophagy genes that associated with the survival and clinical stage of HCC. In addition, the prognostic model can be used to calculate the patient's risk score and these prognosis-related autophagy genes might serve as therapeutic targets.

6.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 3517-3520, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33018762

RESUMO

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technology that modulates the excitability of the brain by delivering weak electric currents to the brain via scalp electrodes. Electrode configuration and injected current intensity are two important parameters in the tDCS design. This simulation study examined three commercially available electrode configurations, i.e. conventional low definition rectangular pad, high-definition Disc, and high-definition 4 x 1 with different electrode distances and different injected current intensity. Simulation results show that increasing the injected current intensity of HD-tDCS mainly increases the electrical field strength for all configurations. Both Disc and 4 x 1 high definition tDCS (HD-tDCS) have better focality than the conventional low-definition rectangular pad. Increasing the inter-electrode distance in HD-tDCS enlarges the electrical field strength and the depth of stimulation but reduces the focality. In motor rehabilitation, a trade-off needs to be made in the tDCS design to allow the electrical field reaching the white matter to facilitate the usage of the cortico-spinal tract without influencing other undesirable regions in the brain.

7.
J Theor Biol ; 509: 110509, 2020 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-33022285

RESUMO

A major challenge in understanding spike-time dependent information encoding in the neural system is the non-linear firing response to inputs of the individual neurons. Hence, quantitative exploration of the putative mechanisms of this non-linear behavior is fundamental to formulating the theory of information transfer in the neural system. The objective of this simulation study was to evaluate and quantify the effect of slowly activating outward membrane current, on the non-linearity in the output of a one-compartment Hodgkin-Huxley styled neuron. To evaluate this effect, the peak conductance of the slow potassium channel (gK-slow) was varied from 0% to 200% of its normal value in steps of 33%. Both cross- and iso-frequency coupling between the input and the output of the simulated neuron was computed using a generalized coherence measure, i.e., n:m coherence. With increasing gK-slow, the amount of sub-harmonic cross-frequency coupling, where the output frequencies (1-8 Hz) are lower than the input frequencies (15-35 Hz), increased progressively whereas no change in iso-frequency coupling was observed. Power spectral and phase-space analysis of the neuronal membrane voltage vs. slow potassium channel activation variable showed that the interaction of the slow channel dynamics with the fast membrane voltage dynamics generates the observed sub-harmonic coupling. This study provides quantitative insights into the role of an important membrane mechanism i.e. the slowly activating outward current in generating non-linearities in the output of a neuron.

8.
Sci Total Environ ; 755(Pt 2): 142648, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33045598

RESUMO

Benzodiazepines (BZDs) are one of the most widely prescribed psychoactive drugs, however their persistence in the receiving environment has raised great concerns about their potential ecological risks. Here we investigated the occurrence, fate and mass loading of 17 BZDs and their 3 transformation products in 11 wastewater treatment plants (WWTPs) in Guangdong province, China. A total of 10 BZDs and 1 transformation product were found in the WWTPs influents, effluents and excess sludge, with concentrations reaching up to 44.5 ng/L (clozapine), 27.1 ng/L (oxazepam) and 62.9 ng/g (clozapine), respectively. The overall removal efficiency varied widely from negative to complete removal in these 11 WWTPs. Mass balance analysis of two representative WWTPs (WWTPA and WWTPB) with different treatment processes showed that their removals were mainly attributed to the sludge adsorption and biodegradation/biotransformation. The total usage of detected BZDs was estimated to be 185 kg/y in Guangdong province, China, while the total emission was 143 kg/y. Based on sewage epidemiology method, the total back-estimated consumption and emissions of BZDs and their transformation products in one district of Guangzhou (WWTPC service area) were 1012 mg/d/1000 people and 10.1 mg/d/1000 people, respectively. The findings from this study demonstrate the persistence of BZDs in WWTPs and also provide basis for further investigation into the potential ecological risks from this group of chemicals.

9.
Acta Pharmacol Sin ; 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32934346

RESUMO

Recent studies demonstrate that diet quercetin (Quer) has obvious bone protective effects on ovariectomized rodents but thus far there is no direct evidence to support the inhibitory effect of Quer on bone loss caused by long-term unloading. In the present study, we investigated whether Quer could prevent bone loss induced by unloading in mice. Mice were subjected to hindlimb suspension (HLS) and received Quer (25, 50, 100 mg· kg-1 ·day-1, ig) for 4 weeks. Before euthanasia blood sample was collected; the femurs were harvested and subjected to MicroCT analysis. We showed that Quer administration markedly improved bone microstructure evidenced by dose-dependently reversing the reduction in bone volume per tissue volume, trabecular number, and bone mineral density, and the increase of trabecular spacing in mice with HLS. Analysis of serum markers and bone histometric parameters confirmed that Quer at both middle and high doses significantly decreased bone resorption-related markers collagen type I and tartrate-resistant acid phosphatase 5b, and increased bone formation-related marker procollagen 1 N-terminal propeptide as compared with HLS group. Treatment with Quer (1, 2, 5 µM) dose-dependently inhibited RANKL-induced osteoclastogenesis through promoting the expression of antioxidant hormone stanniocalcin 1 (STC1) and decreasing ROS generation; knockdown of STC1 blocked the inhibitory effect of Quer on ROS generation. Knockdown of STC1 also significantly promoted osteoclastogenesis in primary osteoclasts. In conclusion, Quer protects bones and prevents unloading-caused bone loss in mice through STC1-mediated inhibition of osteoclastogenesis. The findings suggest that Quer has the potential to prevent and treat off-load bone loss as an alternative supplement.

10.
Brain Res ; 1749: 147136, 2020 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-32980332

RESUMO

Fear-related anxiety disorders, such as social phobia and post-traumatic stress disorder, are partly explained by an uncontrollable state of fear. An emerging literature suggests dopamine receptor-1 (D1 receptor) in the amygdala is involved in the regulation of fear memory. An early study has reported that amygdaloid D1 receptor (D1R) is not coupled to the classic cAMP-dependent signal transduction. Here, we investigated whether SKF83959, a typical D1R agonist that mainly activates a D1-like receptor-dependent phosphatidylinositol (PI) signal pathway, facilitates fear extinction and reduces the return of extinguished fear. Interestingly, long-term loss of fearful memories can be induced through a combination of SKF83959 (1 mg/kg/day, i.p., once daily for one week) pharmacotherapy and extinction training. Furthermore, sub-chronic administration of SKF83959 after fear conditioning reduced fear renewal and reinstatement in the mice. We found that the activation D1R and PI signaling in the amygdala was responsible for the effect of SKF83959 on fear extinction. Additionally, SKF83959 significantly promoted the elevation of brain-derived neurotrophic factor (BDNF) expression, possibly by the cAMP response element binding protein (CREB) -directed gene transcription. Given the beneficial effects on extinction, SKF83959 may emerge as a candidate pharmacological approach for improving cognitive-behavioral therapy on fear-related anxiety disorders.

11.
J Fish Dis ; 43(11): 1409-1418, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32880984

RESUMO

Clonorchis sinensis, an important fish-borne zoonotic trematode, is widely distributed in South-East Asia, especially in China. Infections from human and animal reservoir hosts occur due to the consumption of raw or undercooked fish with C. sinensis metacercariae. This study aimed to evaluate the prevalence of C. sinensis metacercariae in fish in South-East Asia via systematic review and meta-analysis. We searched PubMed, ScienceDirect, China National Knowledge Infrastructure, Wanfang and Chongqing VIP databases for studies published between 1976 and 2020 that are related to the prevalence of C. sinensis metacercariae in fish. Studies were screened with keywords based on inclusion and exclusion criteria. Seventy-one eligible articles were identified, covering three countries: China, Korea and Vietnam. The pooled prevalence of C. sinensis metacercariae in fish from South-East Asia was 30.5%, with 35.1% in China, 29.7% in Korea and 8.4% in Vietnam. In subgroup analyses of climate, season, water source and publication date, the highest prevalence was identified in the Dwb climate type (43.3%), summer (70.2%), river (34.5%) and pre-2001 publications (38.9%), respectively. In comparison, the lowest prevalence was found in the Dfa climate type (14.5%), winter (19.5%), lake (8.0%) and post-2001 publications (23.8%). Meta-regression results indicated that country (p = .009), the published time (p = .035) and water source subgroups (p = .003) may be the source of heterogeneity. Overall, our study indicates that a high prevalence of C. sinensis infections occurs in fish in China, Korea and Vietnam, illuminating a significant public health concern in these countries.

12.
J Immunol Res ; 2020: 2141508, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32908938

RESUMO

Berberine (BBR), a natural compound extracted from a Chinese herb, has been shown to effectively attenuate insulin resistance (IR) and inflammation in the clinic. However, its ameliorative mechanism against IR is not well defined. This study is aimed at investigating the effect of BBR and protein phosphatase, Mg2+/Mn2+-dependent 1B (PPM1B) on IR. Biochemical measurements and liver histopathology were detected using the biochemical analyzer and HE staining in ZDF rats, respectively. Microarray analysis of liver tissues was performed, and differentially expressed gene (DEG) levels were examined by quantitative real-time PCR (qPCR) and Western blot. Additionally, the effect of BBR was also explored in HepG2-IR cells. The glucose oxidase method and the fluorescent glucose analog were used to detect glucose consumption and uptake, respectively. The PKA inhibitor H89, ELISA, qPCR, Western blot, and immunofluorescence staining were employed to estimate the expression levels of related signaling pathways. To evaluate the roles of PPM1B, HepG2-IR cells were stably infected with lentivirus targeting PPM1B. The administration of BBR drastically decreased the body weight, urine volume, blood glucose, blood urea nitrogen (BUN), CHOL, hepatic index levels, and pathologic changes and improved ALB levels in ZDF rats with PPM1B upregulation. Furthermore, BBR effectively improves glucose consumption, uptake, and inflammation in HepG2-IR cells. The knockdown of PPM1B expression aggravated the inflammatory response and glycometabolism disorder in HepG2-IR cells. Mechanistically, a reversal in the expression of cAMP, PKA, PPM1B, PPARγ, LRP1, GLUT4, NF-κB p65, JNK, pIKKß Ser181, IKKß, IRS-1 Ser307, IRS-1, IRS-2 Ser731, IRS-2, PI3K p85, and AKT Ser473 contributes to ameliorate IR in HepG2-IR cells with BBR treatment. Altogether, these results suggest that BBR might regulate IR progression through the regulation of the cAMP, PKA, PPM1B, PPARγ, LRP1, GLUT4, NF-κB p65, JNK, pIKKß Ser181, IKKß, IRS-1 Ser307, IRS-1, IRS-2 Ser731, IRS-2, PI3K p85, and AKT Ser473 expression in the liver.

13.
Fertil Steril ; 2020 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-32912637

RESUMO

OBJECTIVE: To explore the exome and transcriptome characteristics potentially underlying the pathogenesis of varicocele (VE). DESIGN: Experimental study and cohort study. SETTING: Academic research laboratory and university-affiliated hospital. PATIENT(S): Eleven VE patients whose fathers also had VE, plus 151 additional patients and 324 healthy men for variants genotyping; for the rat model, eight Sprague-Dawley male rats. INTERVENTION(S): Partial ligation of renal vein was conducted to establish VE rat models for whole-transcriptome RNA sequencing (RNA-seq). MAIN OUTCOME MEASURE(S): Genes with differential expression and/or harboring potential pathogenic variants detected via RNA-seq and whole-exome sequencing (WES) then subjected to population-based survey to define candidate genes of VE and analyzed via Gene Ontology and Kyoto Encyclopedia of Genes and Genomes to identify VE-involved pathways. RESULT(S): Whole-transcriptome RNA sequencing (RNA-seq) was performed using left spermatic veins of five rat VE models and three controls. We identified 9,688 genes and 18 pathways via RNA-seq, and via WES 160 genes harboring 279 potential deleterious variants and 16 pathways. Nine genes (AAMP, KMT2D, IRS2, SPINT1, IFT122, MKI67, DCHS1, LAMA2, and CBL) had variants in more than one patient who underwent WES, and six of these genes (AAMP, SPINT1, MKI67, IFT122, LAMA2, and DCHS1) showed differential expression. The population-based survey showed that AAMP, SPINT1, and MKI67 were strongly associated with VE risk. Together, two omic 67 data sets revealed four pathways potentially related to VE. CONCLUSION(S): For the first time, we have described the exome and transcriptome characteristics of VE. The bi-omics identified novel candidate genes and pathways involving the occurrence and development of VE.

14.
J Nanobiotechnology ; 18(1): 139, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32993662

RESUMO

Drug therapy of osteoarthritis (OA) is limited by the short retention and lacking of stimulus-responsiveness after intra-articular (IA) injection. The weak acid microenvironment in joint provides a potential trigger for controlled drug release systems in the treatment of OA. Herein, we developed an pH-responsive metal - organic frameworks (MOFs) system modified by hyaluronic acid (HA) and loaded with an anti-inflammatory protocatechuic acid (PCA), designated as MOF@HA@PCA, for the therapy of OA. Results demonstrated that MOF@HA@PCA could smartly respond to acidic conditions in OA microenvironment and gradually release PCA, which could remarkably reduce synovial inflammation in both IL-1ß induced chondrocytes and the OA joints. MOF@HA@PCA also down-regulated the expression of inflammatory markers of OA and promoted the expression of cartilage-specific makers. This work may provide a new insight for the design of efficient nanoprobes for precision theranostics of OA .

15.
Aging (Albany NY) ; 12(17): 16672-16674, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32915771

RESUMO

Pregnant women are susceptible population of COVID-19 which are more likely to have complications and even progress to severe illness. Pregnancy with COVID-19 and neonates are rarely reported. We report a newborn with normal IgM and elevated IgG antibodies born to an asymptomatic infection mother with COVID-19. We assessed whether there was intrauterine vertical transmission potential of COVID-19.

16.
Pharm Biol ; 58(1): 992-998, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32964757

RESUMO

CONTENT: Isochlorogenic acid A, one of the main components of Duhaldea nervosa (Wallich ex Candolle) A. Anderberg (Asteraceae), is a folk medicine used to treat a variety of diseases including fracture and rheumatoid arthritis. Despite its widespread use, the metabolism of isochlorogenic acid A in vivo has not been fully studied. OBJECTIVE: An analytical strategy based on UHPLC-Q-Exactive Orbitrap MS is proposed for the detection and identification of the metabolites of isochlorogenic acid A in rats. MATERIALS AND METHODS: Six male Sprague-Dawley rats (180 ± 20 g) were randomly divided into two groups. Then, blood and tissue samples were obtained after oral administration of isochlorogenic acid A (200 mg/kg). All the samples were pre-treated by the Solid Phase Extraction (SPE) method. Next, the samples were analysed by UHPLC-Q-Exactive Orbitrap MS. Finally, the metabolites were identified based on the metabolomic workflow template. RESULTS: A total of 33 metabolites were identified in rat plasma, with 30 of them being reported for the first time. The distribution of all metabolites in tissues was first investigated, three of them were widely distributed in liver, lungs, and kidneys. The corresponding reactions including methylation, hydrolysis, sulphate conjugation, glucuronide conjugation, as well as their composite reactions, are reported in this study. DISCUSSION AND CONCLUSIONS: This method has wide-scale application prospects in the identification of metabolites. Considering that limited research has been conducted in this area, this study proposes metabolic pathways to further understand mechanisms of isochlorogenic acid A and the forms that are truly effective in vivo.

17.
Brain Sci ; 10(9)2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32961836

RESUMO

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive brain-stimulation technique that transiently modulates cerebral cortex excitability, achieving overall positive results in poststroke motor-function recovery. Excessive inhibition of the ipsilesional-affected hemisphere by the contralesional-unaffected hemisphere has seriously hindered poststroke motor-function recovery. Hence, intracortical disinhibition can be used as an approach to managing poststroke brain injury. This technique promotes neural plasticity for faster motor-function recovery. rTMS relieves unilateral inhibition of the brain function by regulatinga interhemispheric-imbalanced inhibition. This paper summarized 12 studies from 2016 to date, focusing on rTMS on motor function after acute and chronic stroke by regulating the interhemispheric imbalance of inhibitory inputs. Although rTMS studies have shown promising outcomes on recovery of motor functions in stroke patients, different intervention methods may lead to discrepancies in results. A uniform optimal stimulus model cannot routinely be used, mainly due to the stimulus schemes, stroke types and outcome-measuring differences among studies. Thus, the effect of rTMS on poststroke motor-function recovery should be investigated further to standardize the rTMS program for optimal poststroke motor-function recovery. More randomized, placebo-controlled clinical trials with standardized rTMS protocols are needed to ensure the effectiveness of the treatment.

18.
J Hazard Mater ; 399: 123032, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32937710

RESUMO

In this study, magnetic material based reduced graphene oxide (M-rGO) was prepared through co-precipitation and displayed high catalytic efficiency together with persulfate (PS) for simultaneous p-arsanilic acid (p-ASA) decomposition and arsenic removal. Linear sweep voltammetry and chronoamperometric measurements with M-rGO revealed that PS was effectively bound to M-rGO surface and probably formed charge transfer complex, in which M-rGO was pivotal in mediating facile electron transfer. The effects of pH, temperatures, anions, p-ASA concentration, PS, and M-rGO dosages on p-ASA decomposition were studied in the system. Excellent degradation of p-ASA was carried out at a wide range of pH values, which was unattainable by other Fenton-like processes. Under optimal conditions, M-rGO exhibited prominent removal of both p-ASA (98.8 %) and inorganic arsenic (89.8 %). M-rGO had reasonably excellent repeatability and stability, and 77.7 % p-ASA degraded in the third recovered catalyst. The advantages of environmental friendliness, short reaction time, and straightforward synthesis of M-rGO will facilitate the development of heterogeneous Fenton-like catalysts under neutral conditions.

19.
Mol Genet Genomics ; 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32944789

RESUMO

Joubert syndrome (JBTS), a rare genetic disorder resulted from primary cilium defects or basal-body dysfunction, is characterized by agenesis of cerebellar vermis and abnormal brain stem. Both genotypes and phenotypes of JBTS are highly heterogeneous. The identification of pathogenic gene variation is essential for making a definite diagnosis on JBTS. Here, we found that hypoplasia of cerebellar vermis occurred in three male members in a Chinese family. Then, we performed whole exome sequencing to identify a novel missense mutation c.599T > C (p. L200P) in the OFD1 gene which is the candidate gene of X-linked JBTS (JBST10). The following analysis showed that the variant was absent in the 1000 Genomes, ExAC and the 200 female controls; the position 200 Leucine residue was highly conserved across species; the missense variant was predicted to be deleterious using PolyPhen-2, PROVEAN, SIFT and Mutation Taster. The OFD1 expression was heavily lower in the proband and an induced male fetus compared with a healthy male with a wild-type OFD1 gene. The in vitro expression analysis of transiently transfecting c.599T or c.599C plasmids into HEK-293T cells confirmed that the missense mutation caused OFD1 reduction at the protein level. And further the mutated OFD1 decreased the level of Gli1 protein, a read-out of Sonic hedgehog (SHH) signaling essential for development of central neural system. A known pathogenic variant c.515T > C (p. L172P) showed the similar results. All of these observations suggested that the missense mutation causes the loss function of OFD1, resulting in SHH signaling impairs and brain development abnormality. In addition, the three patients have Dandy-Walker malformation, macrogyria and tetralogy of Fallot, respectively, the latter two of which are firstly found in JBTS10 patients. In conclusion, our findings expand the context of genotype and phenotype in the JBTS10 patients.

20.
Artigo em Inglês | MEDLINE | ID: mdl-32894400

RESUMO

A definitive diagnosis of heparin-induced thrombocytopenia (HIT) is difficult to make, especially in patients undergoing cardiac surgery. In this retrospective cohort study, we assessed the platelet count trends and the response to fondaparinux in a population of patients of suspected HIT after pulmonary endarterectomy (PEA). Patients enrolled in this study were over the age of 18 years, and survived longer than 7 days after PEA between January 1, 2011 and December 31, 2015. HIT likelihood was assessed by the 4 T's score and interpreted by our institutional algorithm. 54 patients were operated, and 49 patients met the inclusion criteria. Six patients met the criteria for suspected HIT and were treated with fondaparinux until the platelet recovered. No significant difference was observed of clinical characteristics between intermediate to high HIT likelihood patients (HIT SUSPECTED) and low HIT likelihood patients (NO HIT SUSPECTED). HIT SUSPECTED patients reached platelet count lowest later (about 5.5 days after PEA), while NO HIT SUSPECTED patients is about 4.0 days after PEA. Percentage of platelet counts decrease (> 50%) was larger than NO HIT SUSPECTED patients (< 50%). There was no difference in mortality or residual pulmonary hypertension between HIT SUSPECTED and NO HIT SUSPECTED patients. Two HIT SUSPECTED patients who used heparin after PEA died, the other four survived by replacing heparin or low molecular weight heparin with fondaparinux. Suspected HIT patients should be surveilled carefully. Platelet counts trends may have some hints in the prevention of HIT. Fondaparinux may be effective for patients with suspected HIT.

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