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1.
Biomed Microdevices ; 23(2): 21, 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33821351

RESUMO

Cervical degenerative disease is a common and frequently occurring disease, which seriously affects the health and quality of the life of patients worldwide. Anterior cervical decompression and interbody fusion is currently recognized as the gold standard for the treatment of degenerative cervical spondylosis. Polyetheretherketone (PEEK) has become the prevailing material for cervical fusion surgery. Although PEEK has excellent biocompatibility, it is difficult to form bone connection at its bone-implant interface due to its low surface hydrophilicity and conductivity. It is widely accepted that Ti has excellent osteogenic activity and biocompatibility. In this study, a Ti-PEEK composite cage was prepared by coating Ti on the surface of a PEEK cage using a vacuum plasma spraying technique to enhance the osteogenic property of PEEK. The Ti-PEEK samples were evaluated in terms of their in vitro cellular behaviors and in vivo osteointegration, and the results were compared to a pure PEEK substrate. The skeleton staining and MTS assay indicated that the MC3T3-E1 cells spread and grew well on the surface of Ti-PEEK cages. The osteogenic gene expression and western blot analysis of osteogenic protein showed upregulated bone-forming activity of MC3T3-E1 cells in Ti-PEEK cages. Furthermore, a significant increase in new bone formation was demonstrated on Ti-PEEK implants in comparison with PEEK implants at 12 weeks in a sheep cervical spine fusion test. These results proved that the Ti-PEEK cage exhibited enhanced osseointegrative properties compared to the PEEK cage both in vitro and in vivo.

2.
Pol Arch Intern Med ; 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33825417

RESUMO

INTRODUCTION: Although vitamin K antagonists (VKAs) are recommended as first-line anticoagulants for patients with left ventricular thrombus (LVT), accumulating evidence suggests direct oral anticoagulants (DOACs) could be safe alternatives for VKAs. Efficacy and safety of DOACs should be assessed to justify their usage for LVT patients. OBJECTIVES: To compare the efficacy and safety of DOACs and VKAs for the treatment of LVT. PATIENTS AND METHODS: We performed a meta-analysis of observational studies to compare DOACs to VKAs in LVT patients. The PubMed and EMBASE databases were searched for articles published until November 12, 2020. Pooled effects were estimated using Mantel-Haenszel method and presented as risk ratios (RR) using fixed-effect model. Reporting followed the Meta-analyses of observational studies in epidemiology (MOOSE) guideline. RESULTS: A total of 2467 LVT patients from 13 studies were included. Compared with VKAs, DOACs showed similar efficacy in prevention of stroke or systemic embolism (RR: 0.96, 95% confidence interval [CI]: 0.80-1.16, P = 0.68) and thrombus resolution (RR: 0.88, 95% CI: 0.72-1.09, P = 0.26), but significantly lower risk of stroke (RR: 0.68, 95% CI: 0.47-1.00, P = 0.048). For safety outcomes, DOAC users showed similar risk of any bleedings (RR: 0.94, 95% CI: 0.67-1.31, P = 0.70), but lower risk of clinically relevant bleedings (RR: 0.35, 95% CI: 0.13-0.92, P = 0.03) compared with VKA users. CONCLUSIONS: Compared with VKAs, DOACs acquired similar efficacy and safety profile for patients with LVT, but could reduce the risk of strokes and clinically relevant bleedings.

3.
Science ; 372(6538): 171-175, 2021 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-33833120

RESUMO

Sexual reproduction in angiosperms relies on precise communications between the pollen and pistil. The molecular mechanisms underlying these communications remain elusive. We established that in Arabidopsis, a stigmatic gatekeeper, the ANJEA-FERONIA (ANJ-FER) receptor kinase complex, perceives the RAPID ALKALINIZATION FACTOR peptides RALF23 and RALF33 to induce reactive oxygen species (ROS) production in the stigma papillae, whereas pollination reduces stigmatic ROS, allowing pollen hydration. Upon pollination, the POLLEN COAT PROTEIN B-class peptides (PCP-Bs) compete with RALF23/33 for binding to the ANJ-FER complex, leading to a decline of stigmatic ROS that facilitates pollen hydration. Our results elucidate a molecular gating mechanism in which distinct peptide classes from pollen compete with stigma peptides for interaction with a stigmatic receptor kinase complex, allowing the pollen to hydrate and germinate.

4.
Hum Cell ; 2021 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-33813726

RESUMO

Gallbladder carcinoma (GBC) is a lethal biliary tract malignant neoplasm. Patient-derived primary cancer cell lines (PDPCs) are appropriate models to explore biological characteristics and potential therapeutics; however, there is a lack of PDPCs in GBC. In this study, we aimed to establish and characterize the GBC PDPCs, and further investigated the intra-tumor heterogeneity (ITH). Multi-region sampling (3-9 regions) of the operable tumor tissue samples was used to establish PDPCs. Short tandem repeat genotyping for cell authentication and karyotyping was performed, followed by whole-exome sequencing and RNA sequencing to assess the ITH at the genetic and transcriptional levels, respectively. Thirty-eight PDPCs were successfully established from seven GBC patients and characterized. ITH was observed with a median of 38.3% mutations being heterogeneous (range, 26.6-59.4%) across all patients. Similar with other tumor types, TP53 mutations were always truncal. In addition, there were three genes, KMT2C, CDKN2A, and ARID1A, with truncal mutations in at least two patients. A median of 370 differentially expressed genes (DEGs) was identified per patient. Distinct expression patterns were observed between major histocompatibility complex (MHC) class I and II genes. We found the expression of MHC class II genes in the PDPC samples was closely regulated by CIITA, while that of MHC class I genes were not correlated with CIITA expression. The PDPCs established from GBC patients can serve as novel in vitro models to identify the ITH, which may pave a crucial molecular foundation for enhanced understanding of tumorigenesis and progression.

5.
Food Chem ; 355: 129443, 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33799265

RESUMO

Here, a facile hydrothermal method was used to synthesize highly photoluminescent N-doped carbon dots, and the quantum yields reached 97.1%. Then, a label-free immunosensor based on the inner filter effect of carbon dots was developed for ultrasensitive detection of aflatoxin M1 residues in milk. The detection limit was 0.0186 ng/mL (equivalents to 18.10 ng/kg), which satisfied the most stringent maximum tolerable limit value of 25 ng/kg. Besides, the immunosensor showed a good linear relationship from 0.003 ng/mL to 0.81 ng/mL, and the average recoveries ranged from 79.6% to 112.5% for spiked milk samples, with relative standard deviations ranging from 6.7% to 13.3%. Compared with other immunoassays, the inner filter effect-based immunosensor incorporating fluorescent detection into conventional enzymatic cascade amplification systems and could be a reliable on-site screening method for aflatoxin M1 residue analysis.

6.
Handb Exp Pharmacol ; 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33834276

RESUMO

Nalfurafine has been used clinically in Japan for treatment of itch in kidney dialysis patients and in patients with chronic liver diseases. A one-year post-marketing study showed nalfurafine to be safe and efficacious without producing side effects of typical KOR agonists such as anhedonia and psychotomimesis. In this chapter, we summarize in vitro characterization and in vivo preclinical studies on nalfurafine. In vitro, nalfurafine is a highly potent and moderately selective KOR full agonist; however, whether it is a biased KOR agonist is a matter of debate. In animals, nalfurafine produced anti-pruritic effects in a dose range lower than that caused side effects, including conditioned place aversion (CPA), hypolocomotion, motor incoordination, consistent with the human data. In addition, nalfurafine showed antinociceptive effects in several pain models at doses that did not cause the side effects mentioned above. It appears to be effective against inflammatory pain and mechanical pain, but less so against thermal pain, particularly high-intensity thermal pain. U50,488H and nalfurafine differentially modulated several signaling pathways in a brain region-specific manners. Notably, U50,488H, but not nalfurafine, activated the mTOR pathway, which contributed to U50,488H-induced CPA. Because of its lack of side effects associated with typical KOR agonists, nalfurafine has been investigated as a combination therapy with an MOR ligand for pain treatment and for its effects on opioid use disorder and alcohol use disorder, and results indicate potential usefulness for these indications. Thus, although in vitro data regarding uniqueness of nalfurafine in terms of signaling at the KOR are somewhat equivocal, in vivo results support the assertion that nalfurafine is an atypical KOR agonist with a significantly improved side-effect profile relative to typical KOR agonists.

7.
JCI Insight ; 6(7)2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33830080

RESUMO

No effective systemic treatment is available for patients with unresectable, recurrent, or metastatic mucoepidermoid carcinoma (MEC), the most common salivary gland malignancy. MEC is frequently associated with a t(11;19)(q14-21;p12-13) translocation that creates a CRTC1-MAML2 fusion gene. The CRTC1-MAML2 fusion exhibited transforming activity in vitro; however, whether it serves as an oncogenic driver for MEC establishment and maintenance in vivo remains unknown. Here, we show that doxycycline-induced CRTC1-MAML2 knockdown blocked the growth of established MEC xenografts, validating CRTC1-MAML2 as a therapeutic target. We further generated a conditional transgenic mouse model and observed that Cre-induced CRTC1-MAML2 expression caused 100% penetrant formation of salivary gland tumors resembling histological and molecular characteristics of human MEC. Molecular analysis of MEC tumors revealed altered p16-CDK4/6-RB pathway activity as a potential cooperating event in promoting CRTC1-MAML2-induced tumorigenesis. Cotargeting of aberrant p16-CDK4/6-RB signaling and CRTC1-MAML2 fusion-activated AREG/EGFR signaling with the respective CDK4/6 inhibitor Palbociclib and EGFR inhibitor Erlotinib produced enhanced antitumor responses in vitro and in vivo. Collectively, this study provides direct evidence for CRTC1-MAML2 as a key driver for MEC development and maintenance and identifies a potentially novel combination therapy with FDA-approved EGFR and CDK4/6 inhibitors as a potential viable strategy for patients with MEC.

8.
J Acoust Soc Am ; 149(3): 2072, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33810767

RESUMO

On the quest towards efficiently eliminating noises, the development of a subwavelength sound absorber with the capability of free ventilation remains challenging. Here, we theoretically propose and experimentally demonstrate an asymmetric metamaterial absorber constructed by tuned Mie resonators (MRs) with unbalanced intrinsic losses. The lossy MR layer is highly dissipative to consume the sound energy while the lossless one acts as an acoustically soft boundary. Thus, the absorber presents quasi-perfect absorption (95% in experiment) for sound waves incident from the port nearer the dissipative MR and large-amount reflection (71% in experiment) from the opposite port. Moreover, the fluid dynamics investigation confirms the superior character of free air circulation owing to the ultrasparsity (volume filling ratio as low as 5%) of the absorber and its robustness to the velocity of airflows. Due to the multiple-order resonant modes of MR, we further demonstrate the flexibility of a methodology to extend asymmetric absorptions into multibands. Coupled mode analysis is employed to reveal the physical mechanism and further indicates that sparsity can be tuned by attentively controlling the reference leakage factor and intrinsic loss.

9.
Can J Gastroenterol Hepatol ; 2021: 5557814, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33791253

RESUMO

Objectives: Diagnosis and treatment of primary biliary cholangitis (PBC) are often complicated by hepatic and/or extrahepatic manifestations, which in turn affect the natural course and prognosis of PBC. This study evaluated the clinical characteristics and prognosis of PBC co-occurring with intrahepatic and extrahepatic autoimmune disease (AID). Methods: Clinical data of patients with PBC who were admitted to the Beijing Ditan Hospital from September 2008 to December 2014 were retrospectively reviewed, assessed for other autoimmune diseases, and analyzed statistically. All patients received ursodeoxycholic acid (UDCA) treatment. Results: Data from 505 patients were evaluated. Approximately 35.0% of patients had at least one additional AID. AIDs included Sjögren's syndrome (SS; 26.3%), autoimmune hepatitis (AIH; 7.1%), rheumatoid arthritis (RA; 1.4%), hypothyroidism (0.8%), Graves's thyroiditis (0.6%), systemic lupus erythematosus (SLE; 0.4%), and Hashimoto's thyroiditis (0.2%). No differences in response rates of UDCA were found between the PBC group and the PBC-SS group or PBC complicated with AID group (both P > 0.05). White blood cell (WBC, RR = 1.072, 95% CI: 1.016-1.130, P=0.011), platelet counts (PLT, RR = 0.995, 95% CI: 0.992-0.998, P=0.003), and prothrombin time and international normalized ratio (PT/INR, RR = 1.799, 95% CI: 1.010-3.206, P=0.046) were independent prognostic factors in patients with PBC. The overall survival time of patients in PBC-AIH and PBC-SS groups was shorter than that of those with PBC (P < 0.001). Conclusions: AIH was the most common in hepatic comorbidity. SS was the most frequent extrahepatic comorbidity. WBC, PLT, and PT/INR were independent prognostic factors in patients with PBC. AID coexisted with PBC impaired patients' survival.

10.
BMC Surg ; 21(1): 141, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33740933

RESUMO

BACKGROUND: The open-door laminoplasty is an effective procedure for the treatment of cervical spondylotic myelopathy. However, little information is available about the surgical results of open-door laminoplasty in the treatment of intraspinal tumors. In the present study, we aimed to investigate the clinical effect of open-door laminoplasty with ARCH plate fixation in the treatment of cervical intraspinal tumors. METHODS: This was a retrospective study. From January 2013 to May 2018, 38 patients (13 males and 25 females, the average age of 44 ± 17 years) with cervical intraspinal tumors underwent open-door laminoplasty with ARCH plate fixation in our hospital. The operation time, blood loss, pre- and postoperative visual analog scale (VAS), and Japanese Orthopedic Association (JOA) scores were determined. To determine the radiographic outcomes, cervical X-ray film and magnetic resonance imaging (MRI) were performed before and after the operation, and cervical X-ray sagittal film was used to measure Cobb angle. The clinical data before and after the operation were compared by t-test. RESULTS: A total of 38 patients underwent a successful operation and demonstrated primary healing. The average operation time was 113 ± 12 min. The average blood loss was 120 ± 19 mL. All patients were followed up for 26.1 ± 2.8 months, and the final follow-up time was more than 24 months. VAS scores were much better at 24 months after operation compared with those before the operation, which were decreased from 6.1 ± 1.1 to 1.4 ± 0.7 (t = 32.63, P < 0.01). The JOA score was improved from 9.9 ± 1.5 to 15.5 ± 0.6 (t = - 18.36, P < 0.01), and the mean JOA recovery rate was 79% ± 11% at 24 months after the operation. There was no significant difference in Cobb angle between pre-operation and 24 months after the operation, which was 9.8 ± 2.6 and 10.3 ± 3.1 respectively (t = - 0.61, P > 0.05). Neither spinal malalignment on the coronal plane nor displacement of the laminoplasty flap was observed on postoperative cervical X-ray and MRI examinations at the final follow-up. CONCLUSIONS: Open-door laminoplasty with ARCH plate fixation was a safe and effective surgical approach for the treatment of cervical intraspinal tumors.


Assuntos
Vértebras Cervicais , Laminoplastia , Neoplasias da Coluna Vertebral , Adulto , Placas Ósseas , Vértebras Cervicais/cirurgia , Feminino , Humanos , Laminoplastia/métodos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias da Coluna Vertebral/cirurgia , Resultado do Tratamento
11.
Aging (Albany NY) ; 13(5): 7589-7607, 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33658399

RESUMO

Vulvovaginal atrophy (VVA) is a common menopause-related symptom affecting more than 50% of midlife and older women and cancer patients whose ovarian function are lost or damaged. Regardless of estrogen deficiency, whether other factors such as the gut microbiota play role in VVA have not been thoroughly investigated. To this end, we performed ovariectomy on 12-weeks' old mice and follow-up at 4 weeks after ovariectomy, and observed atrophied vagina and an altered gut microbiota in ovariectomized mice.. We further performed fecal microbiota transplantation with feces from another cohort of ovary-intact fecund female mice to the ovariectomized ones, and found that the vaginal epithelial atrophy was significantly alleviated as well as the gut microbiota was pointedly changed. All these results suggest that ovarian activity has some influence on the gut microbiota, and the latter from the ovary-intact female mice can somehow make the vagina of mice deficient in ovarian function healthier maybe by up-expressing ESR1 in vaginal cells and enhancing regeneration in vagina. This kind of association between gut microbiota and vaginal health need further exploration such that it may provide an alternative treatment by modulating gut microbiota in patients suffering from VVA but may be reluctant to hormone therapy.

12.
Clin Chim Acta ; 517: 156-161, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33662358

RESUMO

The microbial infectious diseases (infectious diseases) represent the leading global public health problem, and the effective treatment depends on rapid and accurate detection of pathogens. Droplet digital PCR (ddPCR), a new assay that combines microfluidics technology with TaqMan-based PCR, provides absolute quantification without the need of the standard curves. With the development of ddPCR, it has become an ideal tool for microorganism detection. In this review, we summarized the major literature with regard to the application of ddPCR in detecting the pathogenic microorganisms of infectious diseases, including bacteria, fungi, and virus. The ddPCR method has the advantages of detecting the targeted DNA of infectious microorganisms, with high sensitivity, high precision, and absolute quantification. Thus, ddPCR has emerged as a promising and reliable tool in detecting pathogenicmicroorganisms.

13.
J Microbiol Methods ; 184: 106202, 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33722638

RESUMO

We reported a modified CFW assay for rapid detection of fungi in blood samples and evaluated its efficacy in vivo and in vitro. The positive rate, sensitivity, and negative predictive values of the modified CFW method were all significantly higher than those of traditional fungal culture and KOH methods.

14.
Environ Pollut ; 280: 116996, 2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33784563

RESUMO

A key challenge for phytoextraction is the identification of high efficiency, growth-supporting, and low cost chelating agents. To date, no substance has satisfied all above criteria. This study investigated nine traditional Chinese herbs and found that Phyllanthus emblica fruit (FPE) extract could be utilised as an optimal chelate for the phytoextraction of cadmium (Cd)-contaminated soils. FPE application into soil at a ratio of 0.1% (w/w) significantly increased extractable Cd (by 43%) compared to the control. The success of FPE as a chelating agent was attributed to high quantities of polyphenol compounds (0.76%) and organic acids (9.6%), in particular, gallic acid (7.6%). Furthermore, antioxidative properties (1.4%) and free amino acids in FPE alleviated Cd-induced oxidant toxicity and enhanced plant biomass. FPE promoted 78% higher phytoextraction efficiency in Platycladus orientalis compared to traditional chelating agents (EDTA). Furthermore, 76% of FPE was degraded 90 days after the initial application, and there was no difference in extractable Cd between the treatment and control. FPE has been commercially produced at a lower market price than other biodegradable chelates. As a commercially available and cost-effective chelator, FPE could be utilised to treat Cd-contaminated soils without adverse environmental impacts.

15.
Cell Rep ; 34(13): 108913, 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33789102

RESUMO

Prdm12 is a key transcription factor in nociceptor neurogenesis. Mutations of Prdm12 cause congenital insensitivity to pain (CIP) from failure of nociceptor development. However, precisely how deletion of Prdm12 during development or adulthood affects nociception is unknown. Here, we employ tissue- and temporal-specific knockout mouse models to test the function of Prdm12 during development and in adulthood. We find that constitutive loss of Prdm12 causes deficiencies in proliferation during sensory neurogenesis. We also demonstrate that conditional knockout from dorsal root ganglia (DRGs) during embryogenesis causes defects in nociception. In contrast, we find that, in adult DRGs, Prdm12 is dispensable for most pain-sensation and injury-induced hypersensitivity. Using transcriptomic analysis, we find mostly unique changes in adult Prdm12 knockout DRGs compared with embryonic knockout and that PRDM12 is likely a transcriptional activator in the adult. Overall, we find that the function of PRDM12 changes over developmental time.

16.
Biomed Res Int ; 2021: 5450397, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33763470

RESUMO

Objective: We aimed to establish a method to determine whether microRNA-193b (miR-193b) levels in ABCA1-labeled serum exosomes might serve as a marker for the diagnosis of Alzheimer's disease. Methods: We used immunocapture methods to determine the levels of ABCA1-labeled exosomal miR-193b in cultures of white blood cells (WBCs), red blood cells (RBCs), mouse hippocampal neuron HT-22 cells, and primary mouse neuronal cells. ABCA1-labeled exosomal miR-193b levels were also evaluated in the cerebrospinal fluid (CSF) and serum of APP/PS1 double-transgenic mice, as well as control subjects (n = 60) and study participants with subjective cognitive decline (SCD, n = 89), stage and mild cognitive impairment (MCI, n = 92), and dementia of the Alzheimer type (DAT, n = 92). Results: ABCA1 levels of exosomes harvested from the medium of HT-22 cells and neurons were significantly higher than those of RBCs and WBCs (P < 0.05). Exosomal ABCA1 from the CSF of APP/PS1 mice were transmitted to the serum of wild-type mice after injection, and high miR-193b levels were observed in both the serum and CSF after injection. The ABCA1-labeled exosomal miR-193b levels were higher in the CSF of MCI and DAT patients compared with the CSF of the control group (P < 0.05). The ABCA1-labeled exosomal miR-193b were also slightly higher (P > 0.05) in the serum of SCD patients and significantly higher in the serum of MCI and DAT patients compared with the serum of the control group (P < 0.05). Conclusion: This study provides a method to capture specific exosomes. Detection of serum exosomes labeled with ABCA1 may facilitate the early diagnosis of AD.

17.
Org Lett ; 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33764790

RESUMO

Here we describe an unprecedented metal-free C(sp3)-H aroylation of amines via visible-light photoredox catalysis, which provides a straightforward route for the construction of a useful α-amino aryl ketone skeleton. Additionally, a number of selected products exhibit good biological activity for protecting PC12 cell damage, which shows that this skeleton has the potential to become a new neuroprotective agent. Finally, a series of mechanism experiments indicate that this transformation undergoes a photoredox catalytic radical-radical cross-coupling pathway.

18.
Artigo em Inglês | MEDLINE | ID: mdl-33734578

RESUMO

Many ribosomal proteins (RPs) not only play essential roles in ribosome biogenesis, but also have "extraribosomal" functions in various cellular processes. RpL36 encodes ribosomal protein L36, a component of the 60S subunit of ribosomes in Drosophila melanogaster. We report here that RpL36 is required for spermatogenesis in D. melanogaster. After showing the evolutionary conservation of RpL36 sequences in animals, we revealed that the RpL36 expression level in fly testes was significantly higher than in ovaries. Knockdown RpL36 in fly testes resulted in a significantly decreased egg hatch rate when these males mated with wild-type females. Furthermore, 76.67% of the RpL36 knockdown fly testes were much smaller in comparison to controls. Immunofluorescence staining exhibited that in the RpL36 knockdown testis hub cell cluster was enlarged, while the number of germ cells, including germ stem cells, was reduced. Knockdown of RpL36 in fly testis caused much fewer or no mature sperms in seminal vesicles. The terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) signal was stronger in RpL36 knockdown fly testes than in the control testes, but the TUNEL-positive cells could not be stained by Vasa antibody, indicating that apoptotic cells are not germ cells. The percentage of pH3-positive cells among the Vasa-positive cells was significantly reduced. The expression of genes involved in cell death, cell cycle progression, and JAK/STAT signaling pathway was significantly changed by RpL36 knockdown in fly testes. These results suggest that RpL36 plays an important role in spermatogenesis, likely through JAK/STAT pathway, thus resulting in defects in cell-cycle progression and cell death in D. melanogaster testes.

19.
Liver Int ; 2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33655714

RESUMO

BACKGROUND/AIMS: Direct-acting antivirals (DAAs) are highly effective in treating chronic hepatitis C virus (HCV)-infected patients. The real-world treatment outcome in Taiwanese patients on a nationwide basis is elusive. METHODS: The Taiwan HCV Registry (TACR) programme is a nationwide registry platform including 48 study sites, which is organized and supervised by the Taiwan Association for the Study of the Liver. The primary endpoint was sustained virological response (SVR12, undetectable HCV RNA 12 weeks after end-of-treatment). RESULTS: A total of 13 951 registered patients with SVR12 data available were analysed (mean age, 63.0 years; female, 55.9%; HCV genotype-1 [GT1], 57.9%; cirrhosis, 38.4%; preexisting hepatocellular carcinoma [HCC], 10.6%; and hepatitis B virus coinfection, 7.7%). The overall SVR12 rate was 98.3%, with 98.7%, 98.0%, 98.4% and 97.4% in treatment-naïve noncirrhotic, treatment-naïve cirrhotic, treatment-experienced noncirrhotic and treatment-experienced cirrhotic patients, respectively. The SVR12 rate was > 95% across all subgroups except treatment-experienced cirrhotic patients who received sofosbuvir/ribavirin (88.7%), treatment-naïve noncirrhotic patients (94.8%) and treatment-experienced cirrhotic (94.8%) patients who received daclatasvir/asunaprevir. The most important factor associated with treatment failure was DAA adherence < 60% ( adjusted odds ratio [aOR]/95% confidence interval [CI]: 117.1/52.4-261.3, P < .001), followed by GT3/GT2 (aOR/CI: 5.78/2.25-14.9, P = .0003 and aOR/CI: 1.55/1.05-2.29, P = .03, compared with GT1), active hepatocellular carcinoma (aOR/CI: 4.29/2.57-7.16, P < .001), the use of sofosbuvir/ribavirin (aOR/CI: 2.51/1.67-3.77, P < .001) and daclatasvir/asunaprevir (aOR/CI: 3.29/1.94-5.58, P < .001), decompensated liver cirrhosis (aOR/CI: 2.50/1.20-5.22, P = .02) and high HCV viral loads (aOR/CI: 2.16/1.57-2.97, P < .001). CONCLUSIONS: DAAs are highly effective in treating Taiwanese HCV patients in the real-world setting. Maintaining DAA adherence and selecting highly efficacious regimens are keys to ensure treatment success.

20.
Sci Rep ; 11(1): 6325, 2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33737581

RESUMO

Cadmium (Cd) presents severe risks to human health and environments. The present study proposed a green option to reduce bioavailable Cd. Rice pot experiments were conducted under continuous flooding with three treatments (T1: intercropping azolla with rice; T2: incorporating azolla into soil before rice transplantation; CK: no azolla). The results showed that azolla incorporation reduced soluble Cd by 37% compared with the CK treatment, which may be explained by the decreased soil redox potential (Eh) (r = 0.867, P < 0.01). The higher relative abundance of Methylobacter observed in azolla incorporation treatment may account for dissolved organic carbon increase (r = 0.694; P < 0.05), and hence decreased the Cd availability for rice. Azolla incorporation increased the abundance of Nitrospira, indicating the potentially prominent role of nitrogen mineralization in increasing rice yields. Further, lower soluble Cd decreased the expression of OsNramp5, but increased OsHMA3 levels in rice roots, which decreased Cd accumulation in grains. Through these effects, azolla incorporation decreased Cd concentrations in rice grains by 80.3% and increased the production by 13.4%. The negligible amount of Cd absorbed by azolla would not increase the risk of long-term application. Thus, intercropping azolla with early rice and incorporating azolla into soil before late rice transplantation can contribute to safe production at large scales of double rice cultivation.

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