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1.
Adv Healthc Mater ; : e2100785, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34212532

RESUMO

Ultrasound treatment is an effective method for accelerating chronic wound healing. However, it is not widely used because traditional ultrasonic probes cannot be conformal to the wound surface, which leads to limitations of use and unstable treatment effects. In addition, the use of liquid coupling agent increases the chance of wound infection. A strategy is proposed to design and fabricate a flexible ultrasonic patch for treating chronic wounds effectively. The piezoelectric ceramic in the patch is discretized into several linearly arranged units, which are integrated on a flexible circuit substrate. A thin hydrogel patch is used as both encapsulation and coupling layer to avoid wound infection and ensure the penetration of ultrasound. The ultrasonic patch is soft, light, and can completely conform to the treatment area. Bending of the patch focuses the sound beams on the center of the bending circle, which achieves control of the target treatment area. Ultrasound treatment experiments are carried out on some type-II diabetic rats. Immunohistochemical (IHC) results indicate that ultrasound accelerates wound healing by activating Rac1 in both dermal and epidermal layers. Treatment results show that wound treated with the ultrasound heals faster than wounds without. The healing time is shortened by ≈40%.

2.
Macromol Rapid Commun ; : e2100333, 2021 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-34219313

RESUMO

Polymerization-induced self-assembly via reversible addition-fragmentation chain transfer (RAFT)-mediated emulsion polymerization is an emerging method in which macro-RAFT agents are chain extended with hydrophobic monomers in water to form block copolymer nano-objects. However, almost all RAFT-mediated emulsion polymerizations are limited to AB diblock copolymers by using monofunctional macro-RAFT agents with non-reactive end groups. In this study, the first investigation on how the reactive end group of macro-RAFT agent affects RAFT-mediated emulsion polymerization is reported. Three macro-RAFT agents with different end groups are synthesized and employed in RAFT-mediated emulsion polymerization. Effects of end groups on morphologies of block copolymer nano-objects and polymerization process are studied. Block copolymer nano-objects prepared by using an asymmetric difunctional macro-RAFT agent can be functionalized by further chain extension on the surface. It is expected that the current study will not only expand the scope of RAFT-mediated emulsion polymerization, but also provide a novel strategy to prepare functional polymer nanoparticles.

3.
J Alzheimers Dis ; 2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34219730

RESUMO

BACKGROUND: Phospholipid transfer protein (PLTP) belongs to the lipid transfer glycoprotein family. Studies have shown that it is closely related to Alzheimer's disease (AD); however, the exact effect and mechanism remain unknown. OBJECTIVE: To observe the effect of PLTP overexpression on behavioral dysfunction and the related mechanisms in APP/PS1/Tau triple transgenic (3×Tg-AD) mice. METHODS: AAV-PLTP-EGFP was injected into the lateral ventricle to induce PLTP overexpression. The memory of 3×Tg-AD mice and wild type (WT) mice aged 10 months were assessed using Morris water maze (MWM) and shuttle-box passive avoidance test (PAT). Western blotting and ELISA assays were used to quantify the protein contents. Hematoxylin and eosin, Nissl, and immunochemistry staining were utilized in observing the pathological changes in the brain. RESULTS: 3×Tg-AD mice displayed cognitive impairment in WMW and PAT, which was ameliorated by PLTP overexpression. The histopathological hallmarks of AD, senile plaques and neurofibrillary tangles, were observed in 3×Tg-AD mice and were improved by PLTP overexpression. Besides, the increase of amyloid-ß42 (Aß 42) and Aß 40 were found in the cerebral cortex and hippocampus of 3×Tg-AD mice and reversed by PLTP overexpression through inhibiting APP and PS1. PLTP overexpression also reversed tau phosphorylation at the Ser404, Thr231 and Ser199 of the hippocampus in 3×Tg-AD mice. Furthermore, PLTP overexpression induced the glycogen synthase kinase 3ß (GSK3ß) inactivation via upregulating GSK3ß (pSer9). CONCLUSION: These results suggest that PLTP overexpression has neuroprotective effects. These effects are possibly achieved through the inhibition of the Aß production and tau phosphorylation, which is related to GSK3ß inactivation.

4.
Mol Genet Genomic Med ; : e1747, 2021 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-34302448

RESUMO

BACKGROUND: Hypoxia within the plateau has a negative effect on skeletal muscle and may play a role in the development of sarcopenia in humans. Tibetans having lived in the Qinghai-Tibet Plateau for thousands of years, are a high-risk group for sarcopenia; however, they have a distinctive suite of genetic traits that enable them to tolerate environmental hypoxia and are genetically significantly different from Han Chinese and other lowland populations. Sarcopenia has been consistently found to be associated with single-nucleotide polymorphisms, but few studies have investigated the role of single-nucleotide polymorphisms in a range of muscle phenotypes and sarcopenia in Tibetan peoples. METHODS: Our study aimed to investigate the skeletal muscle mass and fat mass of 160 Tibetans (80 men and 80 women) from Lhasa (altitude of 3600 meters) and analyze the association between the polymorphisms of fat mass and obesity protein (FTO) rs9939609, FTO rs9936385, activin type IIB receptor (ACVR2B) rs2276541, insulin receptor substrate 1 (IRS1) 2943656 and sarcopenia. RESULT: FTO rs9939609 and rs9936385 polymorphisms were associated with lower limb skeletal muscle mass and sarcopenia for Tibetan women, and TT homozygotes had a higher risk for sarcopenia. But ACVR2B rs2276541 and IRS1 2943656 polymorphisms were unassociated with sarcopenia in Tibetan. CONCLUSION: In Tibetans, FTO rs9939609 and rs9936385 polymorphisms were associated with sarcopenia, and ACVR2B rs2276541 and IRS1 2943656 polymorphisms were unassociated with sarcopenia.

5.
Front Immunol ; 12: 711939, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34305952

RESUMO

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Recently was been found that pyroptosis is a unique form of proinflammatory programmed death, that is different from apoptosis. A growing number of studies have investigated pyroptosis and its relationship with sepsis, including the mechanisms, role, and relevant targets of pyroptosis in sepsis. While moderate pyroptosis in sepsis can control pathogen infection, excessive pyroptosis can lead to a dysregulated host immune response and even organ dysfunction. This review provides an overview of the mechanisms and potential therapeutic targets underlying pyroptosis in sepsis identified in recent decades, looking forward to the future direction of treatment for sepsis.

6.
Int J Biol Macromol ; 2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34310992

RESUMO

To clarify the mechanism of semicarbazide-modified α-lactalbumin (SEM-LA)-mediated cytotoxicity, we investigated its effect on human U937 leukemia cells and MCF-7 breast cancer cells in the current study. SEM-LA induced apoptosis in U937 cells, which showed increased NOX4 expression, procaspase-8 degradation, and t-Bid production. FADD depletion inhibited SEM-LA-elicited caspase-8 activation, t-Bid production, and cell death, indicating that SEM-LA activated death receptor-mediated apoptosis in U937 cells. SEM-LA stimulated Ca2+-mediated Akt activation, which in turn increased Sp1- and p300-mediated NOX4 transcription. The upregulation of NOX4 expression promoted ROS-mediated p38 MAPK phosphorylation, leading to protein phosphatase 2A (PP2A)-regulated tristetraprolin (TTP) degradation. Remarkably, TTP downregulation increased the stability of TNF-α mRNA, resulting in the upregulation of TNF-α protein expression. Abolishment of Ca2+-NOX4-ROS axis-mediated p38 MAPK activation attenuated SEM-LA-induced TNF-α upregulation and protected U937 cells from SEM-LA-mediated cytotoxicity. The restoration of TTP expression alleviated the effect of TNF-α upregulation and cell death induced by SEM-LA. Altogether, the data in this study demonstrate that SEM-LA activates TNF-α-mediated apoptosis in U937 cells through the NOX4/p38 MAPK/PP2A axis. We think that a similar pathway can also explain the death of MCF-7 human breast cancer cells after SEM-LA treatment.

7.
Elife ; 102021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34313218

RESUMO

Sleep is essential in maintaining physiological homeostasis in the brain. While the underlying mechanism is not fully understood, a 'synaptic homeostasis' theory has been proposed that synapses continue to strengthen during awake, and undergo downscaling during sleep. This theory predicts that brain excitability increases with sleepiness. Here, we collected transcranial magnetic stimulation (TMS) measurements in 38 subjects in a 34-hour program, and decoded the relationship between cortical excitability and self-report sleepiness using advanced statistical methods. By utilizing a combination of partial least squares (PLS) regression and mixed-effect models, we identified a robust pattern of excitability changes, which can quantitatively predict the degree of sleepiness. Moreover, we found that synaptic strengthen occurred in both excitatory and inhibitory connections after sleep deprivation. In sum, our study provides supportive evidence for the synaptic homeostasis theory in human sleep and clarifies the process of synaptic strength modulation during sleepiness.

8.
J Environ Manage ; 296: 113252, 2021 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-34261035

RESUMO

The study uses an emerging soil treatment technology, the Multi-Soil Layering System (MSL), which is composed of the zeolite permeability layers (PL) and the soil mixture block layers (SMB). The experimental results show that the SMBs with iron particle (SMB-I) removed more than 83% of the total phosphorus (P) pollution in the water, and the outflow sewage concentration is 9.6 mg/L. In contrast, the SMBs with red clay (SMB-R) has 23% removal rate, and the outflow sewage concentration is 46.45 mg/L. Only 0.013 mg/L Fe concentration was detected in the SMB-R system and release of Fe from red soil is hardly achieved under neutral water environment. The SMB-R and SMB-I systems reduced 108.89 mg/g and 20.93 mg/g respectively and the SMB-R had higher removal efficiency of P per gram released Fe. The chromaticity problem of the effluent water in the SMB-I is up to 225 platinum cobalt, and that of the SMB-R is 172 platinum cobalt. Adding 10 g oyster shell (slice-only) and/or 0.65 g polyglutamic acid have effectively removed up to 99% 25-mg/L Fe in the effluent water; the chromaticity problem caused by Fe effluent was successfully solved. Furthermore, the iron particle has the highest unit cost among the materials in the SMBs (US$1.47/kg in lab and US$0.12/kg in field). Removal of 1 mg/L TP in the MSL system costs US$0.036 (by lab) in terms of removal TP rate in the laboratory was 83% and is economically feasible in field development.

9.
Artigo em Inglês | MEDLINE | ID: mdl-34251273

RESUMO

Autosomal dominant tubulointerstitial kidney disease (ADTKD)-uromodulin (UMOD) is the most common non-polycystic genetic kidney disease, but it remains unrecognized due to its clinical heterogeneity and lack of screening test. Moreover, clinical feature being a poor predictor of the disease outcome further highlights the need for development of mechanistic biomarkers in ADTKD. However, low abundant urinary proteins secreted by thick ascending limb (TAL) cells, where UMOD is synthesized, have posed a challenge on detection of biomarkers in ADTKD-UMOD. In the CRISPR/Cas9-generated murine model and patients with ADTKD-UMOD, we find that immunoglobulin heavy chain-binding protein (BiP), an ER chaperone, was exclusively upregulated by mutant UMOD in TAL and easily detected by Western blot in the urine at an early stage of disease. However, even the most sensitive ELISA failed to detect urinary BiP in affected individuals. We therefore developed an ultrasensitive, plasmon-enhanced fluorescence-linked immunosorbent assay (p-FLISA) to quantify urinary BiP concentration by harnessing the newly invented ultrabright fluorescent nanoconstruct, termed "plasmonic fluor" (Nat Biomed Eng 2020). p-FLISA demonstrated that urinary BiP excretion was significantly elevated in ADTKD-UMOD patients compared with unaffected controls, which may have potential utility in risk stratification, disease activity monitoring, disease progression prediction, and guidance of ER-targeted therapies in ADTKD.

10.
Artigo em Inglês | MEDLINE | ID: mdl-34200689

RESUMO

Emergency units have been gradually recognized as important settings for palliative care initiation, but require precise palliative care assessments. Patients with different illness trajectories are found to differ in palliative care referrals outside emergency unit settings. Understanding how illness trajectories associate with patient traits in the emergency department may aid assessment of palliative care needs. This study aims to investigate the timing and acceptance of palliative referral in the emergency department among patients with different end-of-life trajectories. Participants were classified into three end-of-life trajectories (terminal, frailty, organ failure). Timing of referral was determined by the interval between the date of referral and the date of death, and acceptance of palliative care was recorded among participants eligible for palliative care. Terminal patients had the highest acceptance of palliative care (61.4%), followed by those with organ failure (53.4%) and patients with frailty (50.1%) (p = 0.003). Terminal patients were more susceptible to late and very late referrals (47.4% and 27.1%, respectively) than those with frailty (34.0%, 21.2%) and with organ failure (30.1%, 18.8%) (p < 0.001, p = 0.022). In summary, patients with different end-of-life trajectories display different palliative care referral and acceptance patterns. Acknowledgement of these characteristics may improve palliative care practice in the emergency department.


Assuntos
Hospitais para Doentes Terminais , Cuidados Paliativos , Serviço Hospitalar de Emergência , Humanos , Encaminhamento e Consulta , Estudos Retrospectivos
11.
Intern Emerg Med ; 2021 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-34304351

RESUMO

Given the increasing burden of acute myocardial infarction (AMI) in China, regional cooperative rescue systems have been constructed based on chest pain centers (CPCs). This study evaluated the effects of these regional cooperative rescue systems on reperfusion time and prognosis of AMI patients. This study included 1937 AMI patients, divided into two groups according to the date of admission, group A (July 2017-June 2018) and group B (July 2018-June 2019). Reperfusion time, the fatality rate for any cause during hospitalization, and the incidence of major adverse cardiovascular and cerebrovascular events (MACCE) in the 6 months following discharge were compared between the two groups. The proportion of patients treated within the guideline goals for first medical contact to balloon (FMC-to-B) time showed improvement from 40.7% in group A to 50.4% in group B (P = 0.005). The fatality rate for any cause (5.5% vs. 8.0%, P = 0.026) during hospitalization was lower in the B group compared to the A group. Multivariate logistic regression analysis revealed that the fatality rate for any cause (OR 0.614, 95% CI 0.411-0.918, P = 0.017) was significantly lower in group B compared with group A. No significant differences were detected between the two groups for the incidence of MACCE and death for any cause at 6 months using the log-rank test and multivariate Cox regression analysis. The improvement of regional cooperative rescue systems shortened system delays and reduced in-hospital deaths. Although the system has resulted in some substantial improvements, additional improvement is needed.

12.
Oxid Med Cell Longev ; 2021: 6670579, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34285766

RESUMO

Ischemia-reperfusion injury (IRI) has indeed been shown as a main complication of hepatectomy, liver transplantation, trauma, and hypovolemic shock. A large number of studies have confirmed that microvascular and parenchymal damage is mainly caused by reactive oxygen species (ROS), which is considered to be a major risk factor for IRI. Under normal conditions, ROS as a kind of by-product of cellular metabolism can be controlled at normal levels. However, when IRI occurs, mitochondrial oxidative phosphorylation is inhibited. In addition, oxidative respiratory chain damage leads to massive consumption of adenosine triphosphate (ATP) and large amounts of ROS. Additionally, mitochondrial dysfunction is involved in various organs and tissues in IRI. On the one hand, excessive free radicals induce mitochondrial damage, for instance, mitochondrial structure, number, function, and energy metabolism. On the other hand, the disorder of mitochondrial fusion and fission results in further reduction of the number of mitochondria so that it is not enough to clear excessive ROS, and mitochondrial structure changes to form mitochondrial membrane permeable transport pores (mPTPs), which leads to cell necrosis and apoptosis, organ failure, and metabolic dysfunction, increasing morbidity and mortality. According to the formation mechanism of IRI, various substances have been discovered or synthesized for specific targets and cell signaling pathways to inhibit or slow the damage of liver IRI to the body. Here, based on the development of this field, this review describes the role of mitochondria in liver IRI, from aspects of mitochondrial oxidative stress, mitochondrial fusion and fission, mPTP formation, and corresponding protective measures. Therefore, it may provide references for future clinical treatment and research.

13.
Mol Cell Endocrinol ; 535: 111392, 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34246727

RESUMO

Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder in reproductive-aged women, and its pathogenesis is still under debate. Recent studies suggest crucial roles for microRNAs (miRNAs) in PCOS development. The let-7 family miRNAs constitute the most abundant miRNAs in human granulosa cells (GCs), and plays an important role in follicular development. However, research on the let-7e implications of the non-hyperandrogenic (non-HA) phenotype remains unclear. This study aimed at determining the role of let-7e in the progression of PCOS. We performed quantitative real-time PCR to examine the levels of let-7e in fifty-two non-HA PCOS patients and fifty-two controls. A receiver operating characteristic (ROC) curve were used to reveal the diagnostic value of let-7e in non-HA PCOS. Using an immortalized human granulosa cell line, KGN, we investigated the influence of let-7e on cell proliferation and autophagy. Our data substantiated the expression of let-7e was significantly increased in non-HA PCOS group, and associated with an increased antral follicle count. The ROC curve indicated a major separation between non-HA PCOS group and the control group. Let-7e knockdown suppressed cell proliferation and enhanced cell autophagy by activating p21 pathway. Conversely, let-7e overexpression promoted cell proliferation and inhibited cell autophagy by suppressing p21 pathway. Our results indicate that increased let-7e levels in non-HA PCOS GCs may contribute to excessive follicular activation and growth, thereby involving in the pathogenesis of PCOS. Let-7e may thus be a potential therapeutic target in non-HA PCOS.

14.
Nutrients ; 13(6)2021 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-34204322

RESUMO

Previous studies have shown links between heavy metals and many health issues. However, data on the association between heavy metals and mortality in the general population are still limited. Therefore, the aim of this study was to investigate the relationship between heavy metals and overall mortality in the general population. We enrolled 2497 participants (1001 males and 1496 females) living in southern Taiwan, and measured levels of seven heavy metals: lead (Pb) in blood and cadmium (Cd), nickel (Ni), copper (Cu), chromium (Cr), manganese (Mn) and arsenic (As) in urine. The median follow-up period was 41.8 (4-50) months, during which 40 (1.6%) patients died. Compared to the participants who survived, those who died had higher urine Cd, higher urine Cu and lower urine Mn levels. Multivariate analysis showed that high urine Cd (per 1 µg/L; hazard ratio [HR], 1.352; 95% confidence interval [CI], 1.089-1.680; p = 0.006), high urine Cu (per 1 µg/dL; HR, 1.350; 95% CI, 1.151-1.583; p < 0.001), and low urine Mn (per 1 µg/L; HR, 0.717; 95% CI, 0.557-0.923; p = 0.010) were associated with increased overall mortality. In conclusion, our results demonstrated that high levels of urine Cd and Cu and low urine Mn level were associated with increased overall mortality in the general population.

15.
Artigo em Inglês | MEDLINE | ID: mdl-34205053

RESUMO

BACKGROUND: The incidence rates of lip and oral cancer have continued to increase, and prognosis is associated with a country's socioeconomic status. The mortality-to-incidence ratio (MIR) is a reasonable indicator of disparities in cancer screening and treatment. In this study, we aimed to understand the association between economic status and cancer prognosis. METHODS: Data were obtained from the Global Cancer Observatory (GLOBOCAN) and the World Health Organization (WHO). The MIRs were compared to evaluate the correlation with the human development index (HDI), the current health expenditure (CHE), and the ratio of CHE over gross domestic product (CHE/GDP) disparities via Spearman's rank correlation coefficient. RESULTS: The results showed that Asia had the most cases and deaths. In addition, they showed a significant association (p < 0.001, p = 0.005, and p < 0.001, respectively) of the crude rate (CR) of incidence with the HDI, the CHE, and the CHE/GDP. However, their associations with mortality rate (p = 0.303, p = 0.997, and p = 0.101) were not significant. Regarding the correlation of the MIRs, the results revealed a significant association with the HDI, the CHE, and the CHE/GDP (p < 0.001, p < 0.001, and p < 0.001, respectively). CONCLUSION: Countries with higher HDI, CHE per capita, and CHE/GDP tend to have lower MIRs, which indicates favorable clinical outcomes.


Assuntos
Gastos em Saúde , Neoplasias Bucais , Ásia , Saúde Global , Humanos , Incidência , Lábio , Neoplasias Bucais/epidemiologia
16.
Medicine (Baltimore) ; 100(28): e26624, 2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34260550

RESUMO

ABSTRACT: Acute gastrointestinal injury (AGI) is commonly present in patients with acute pancreatitis (AP). It is often difficult to predict gastrointestinal function in the early stage due to lack of reliable markers. We aimed to assess whether early plasma trefoil factor 2 (TFF-2) is a potential predictor for AGI.Fifty one patients were included for the onset of AP (from developing abdominal pain) within 72 hours in this prospective observational single-center study from January 2013 to July 2015. Among them 23 patients were classified as mild, 17 as moderately severe, and 11 as severe according to 2012 Atlanta classification. Plasma samples were collected only once at admission to the ICU. Twenty samples of healthy adults were also collected as control. The TFF-2 levels were determined by using a human TFF-2 enzyme-linked immunoassay. AGI grades from 1st to 7th day after admission were observed.The plasma TFF-2 levels among AP patients in early stage were significantly higher than healthy controls (766.41 ng/mL vs 94.37 ng/mL, P < .0001). The correlations between TFF-2 levels and AGI grades from 1st to 4th day after admission were positive (r = 0.47, 0.43, 0.42, 0.40 respectively, P < .05). As a predictor of acute gastrointestinal failure, plasma TFF-2 was superior to others: Acute Physiology and Chronic Health Evaluation II, sequential organ failure assessment, procalcitonin, C-reactive protein, serum calcium. In addition, TFF-2 increased along with the severity of AP (r = 0.554, P < .0001) and associated with Acute Physiology and Chronic Health Evaluation II, sequential organ failure assessment, C-reactive protein, serum calcium.The plasma TFF-2 levels were increased in patients in early stage of AP and correlated with AGI grades and disease severity in our study. TFF-2 might be a potential predictor for acute gastrointestinal failure in patients with AP.

17.
J Investig Med ; 2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34282046

RESUMO

Sonographic septation is associated with prolonged hospitalization and increased mortality in patients diagnosed with empyema. However, it is unknown whether sonographic septation is associated with complicated parapneumonic effusion (CPPE) or the need for invasive procedures among patients with pneumonia. In this retrospective study, we included 180 patients with non-purulent neutrophilic exudative pleural effusion secondary to pulmonary infections such as pneumonia and lung abscess. We performed univariate and multivariate logistic regression analyses, including baseline clinical characteristics, values from blood samples, and sonographic echogenicity, to identify variables correlated with CPPE and the need for invasive procedures. Seventy of the 180 included patients (38.89%) displayed sonographic septation. Multivariate logistic regression analysis identified that sonographic septation (adjusted OR (AOR)=3.38 (95% CI 1.64 to 6.98), p=0.001) and younger age (AOR=2.63 (95% CI 1.24 to 5.58), p=0.012) were independently associated with CPPE. With regard to treatment strategy, sonographic septation (AOR 9.06 (95% CI 3.71 to 22.11), p<0.001) and total serum protein level (AOR=1.80 (95% CI 1.13 to 2.86), p=0.013) were independently associated with the need for subsequent invasive procedures in patients with CPPE using multivariate logistic regression analysis. Sonographic septation is a useful predictor of CPPE and may imply the need for early invasive procedures.

18.
Nat Biotechnol ; 2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34282325

RESUMO

RNA modifications, such as N6-methyladenosine (m6A), modulate functions of cellular RNA species. However, quantifying differences in RNA modifications has been challenging. Here we develop a computational method, xPore, to identify differential RNA modifications from nanopore direct RNA sequencing (RNA-seq) data. We evaluate our method on transcriptome-wide m6A profiling data, demonstrating that xPore identifies positions of m6A sites at single-base resolution, estimates the fraction of modified RNA species in the cell and quantifies the differential modification rate across conditions. We apply xPore to direct RNA-seq data from six cell lines and multiple myeloma patient samples without a matched control sample and find that many m6A sites are preserved across cell types, whereas a subset exhibit significant differences in their modification rates. Our results show that RNA modifications can be identified from direct RNA-seq data with high accuracy, enabling analysis of differential modifications and expression from a single high-throughput experiment.

19.
Macromol Biosci ; : e2100191, 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34263547

RESUMO

Human organoids mimic the physiology and tissue architecture of organs and are of great significance for promoting the study of human diseases. Traditionally, organoid cultures rely predominantly on animal or tumor-derived extracellular matrix (ECM), resulting in poor reproducibility. This limits their utility in for large-scale drug screening and application for regenerative medicine. Recently, synthetic polymeric hydrogels, with high biocompatibility and biodegradability, stability, uniformity of compositions, and high throughput properties, have emerged as potential materials for achieving 3D architectures for organoid cultures. Compared to conventional animal or tumor-derived organoids, these newly engineered hydrogel-based organoids more closely resemble human organs, as they are able to mimic native structural and functional properties observed in-situ. In this review, recent developments in hydrogel-based organoid culture will be summarized, emergent hydrogel technology will be highlighted, and future challenges in applying them to organoid culture will be discussed.

20.
Artigo em Inglês | MEDLINE | ID: mdl-34263995

RESUMO

Hypertension is a frequent manifestation of chronic kidney disease but the ideal blood pressure (BP) target in patients with coronary artery disease (CAD) with end-stage renal disease (ESRD) (eGFR < 15 ml/min/1.73m2 ) still unclear. The authors aimed to investigate the ideal achieved BP in ESRD patients with CAD after coronary intervention. Five hundred and seventy-five ESRD patients who had undergone percutaneous coronary interventions (PCIs) were enrolled and their clinical outcomes were analyzed according to the category of systolic BP (SBP) and diastolic BP (DBP) achieved. The clinical outcomes included major cardiovascular events (MACE) and MACE plus hospitalization for congestive heart failure (total cardiovascular (CV) event).The mean systolic BP was 135.0 ± 24.7 mm Hg and the mean diastolic BP was 70.7 ± 13.1 mm Hg. Systolic BP 140-149 mm Hg and diastolic BP 80-89 mm Hg had the lowest MACE (11.0%; 13.2%) and total CV event (23.3%; 21.1%). Patients with systolic BP < 120 mm Hg had a higher risk of MACE (HR: 2.01; 95% CI: 1.17-3.46, p = .008) than those with systolic BP 140-149 mm Hg. Patients with systolic BP ≥ 160 mm Hg (HR: 1.84; 95% CI, 3.27-1.04, p = .04) and diastolic blood BP ≥ 90 mm Hg (HR: 2.19; 95% CI: 1.15-4.16, p = .02) had a higher risk of total CV event rate when compared to those with systolic BP 140-149 mm Hg and diastolic BP 80-89 mm Hg. A J-shaped association between systolic (140-149 mm Hg) and diastolic (80-89 mm Hg) BP and decreased cardiovascular events for CAD was found in patients with ESRD after undergoing PCI in non-Western population.

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