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1.
Nat Cell Biol ; 22(10): 1276-1285, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33005030

RESUMO

Breast cancer brain metastasis (BCBM) is a devastating disease. Radiation therapy remains the mainstay for treatment of this disease. Unfortunately, its efficacy is limited by the dose that can be safely applied. One promising approach to overcoming this limitation is to sensitize BCBMs to radiation by inhibiting their ability to repair DNA damage. Here, we report a DNA repair suppressor, leucine-rich repeat-containing protein 31 (LRRC31), that was identified through a genome-wide CRISPR screen. We found that overexpression of LRRC31 suppresses DNA repair and sensitizes BCBMs to radiation. Mechanistically, LRRC31 interacts with Ku70/Ku80 and the ataxia telangiectasia mutated and RAD3-related (ATR) at the protein level, resulting in inhibition of DNA-dependent protein kinase, catalytic subunit (DNA-PKcs) recruitment and activation, and disruption of the MutS homologue 2 (MSH2)-ATR module. We demonstrate that targeted delivery of the LRRC31 gene via nanoparticles improves the survival of tumour-bearing mice after irradiation. Collectively, our study suggests LRRC31 as a major DNA repair suppressor that can be targeted for cancer radiosensitizing therapy.

2.
Sci Robot ; 5(44)2020 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-33022610

RESUMO

The aerobatic maneuvers of swifts could be very useful for micro aerial vehicle missions. Rapid arrests and turns would allow flight in cluttered and unstructured spaces. However, these decelerating aerobatic maneuvers have been difficult to demonstrate in flapping wing craft to date because of limited thrust and control authority. Here, we report a 26-gram X-wing ornithopter of 200-millimeter fuselage length capable of multimodal flight. Using tail elevation and high thrust, the ornithopter was piloted to hover, fly fast forward (dart), turn aerobatically, and dive with smooth transitions. The aerobatic turn was achieved within a 32-millimeter radius by stopping a dart with a maximum deceleration of 31.4 meters per second squared. In this soaring maneuver, braking was possible by rapid body pitch and dynamic stall of wings at relatively high air speed. This ornithopter can recover to glide stability without tumbling after a 90-degree body flip. We showed that the tail presented a strong stabilizing moment under high thrust, whereas the wing membrane flexibility alleviated the destabilizing effect of the forewings. To achieve these demands for high thrust, we developed a low-loss anti-whirl transmission that maximized thrust output by the flapping wings to 40 grams in excess of body weight. By reducing the reactive load and whirl, this indirect drive consumed 40% less maximum electrical power for the same thrust generation than direct drive of a propeller. The triple roles of flapping wings for propulsion, lift, and drag enable the performance of aggressive flight by simple tail control.

3.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 3909-3912, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33018855

RESUMO

Haptic feedback allows an individual to identify various object properties. In this preliminary study, we determined the performance of stiffness recognition using transcutaneous nerve stimulation when a prosthetic hand was moved passively or was controlled actively by the subjects. Using a 2x8 electrode grid placed along the subject's upper arm, electrical stimulation was delivered to evoke somatotopic sensation along their index finger. Stimulation intensity, i.e. sensation strength, was modulated using the fingertip forces from a sensorized prosthetic hand. Object stiffness was encoded based on the rate of change of the evoked sensation as the prosthesis grasped one of three objects of different stiffness levels. During active control, sensation was modulated in real time as recorded forces were converted to stimulation amplitudes. During passive control, prerecorded force traces were randomly selected from a pool. Our results showed that the accuracy of object stiffness recognition was similar in both active and passive conditions. A slightly lower accuracy was observed during active control in one subject, which indicated that the sensorimotor integration processes could affect haptic perception for some users.

4.
J Orthop Surg Res ; 15(1): 461, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33028358

RESUMO

PURPOSE: Non-surgical treatment of primary patellar dislocation has a high risk of recurrent dislocation; thus, we tried to identify injuries in which sites of the medial patellofemoral ligament (MPFL) were most associated with recurrent dislocation by analyzing relevant original literature in order to provide improved suggestions on early surgical treatment. METHODS: According to the preset retrieval strategy, the original studies were retrieved until January 2020 using MEDLINE, Embase and Cochrane Library. Review Manager 5.3 software was used to summarize and compare the differences of recurrent dislocation of MPFL injuries at different attachments. RESULTS: Although the incidence of recurrent patellar dislocation at the femoral attachment of MPFL was higher overall (femoral only vs. patellar only vs. combined: 37.6% vs. 32.3% vs. 35.8%), no statistical difference was found among the three groups (femoral only vs. patellar only, RR = 1.32 [95% CI 0.89-1.95]; P = 0.17) (femoral only vs. combined, RR = 1.15 [95% CI 0.59-2.22]; P = 0.68) (patellar only vs. combined, RR = 0.94 [95% CI 0.69-1.29]; P = 0.72). In addition, the sulcus angle of recurrent dislocation group is significantly greater than that in the non-recurrent dislocation group (MD = 3.06 [95% CI 0.42-5.70]; P = 0.02). CONCLUSIONS: Based on the pooled data collected from the original studies available, the risk of recurrent patellar dislocation due to damage to the MPFL at different sites did not differ. Additionally, the sulcus angle in the group with recurrent dislocation was considerably higher when comparing with the group without recurrent dislocation, that is, the shallower and flatter of the trochlear groove, the higher the risk of recurrent patellar dislocation.

5.
Surg Endosc ; 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33037491

RESUMO

BACKGROUND: The goal of this study was to compare the efficacy and safety of needle-knife fistulotomy (NKF) to that of conventional cannulation methods (CCMs) when used for primary biliary access in patients with duodenal papillary tumors. METHODS: Consecutive patients who had duodenal papillary tumors and who underwent endoscopic retrograde cholangiopancreatography (ERCP) were retrospectively enrolled. Successful cannulation rates, cannulation and procedure times, and the prevalence of adverse events were compared between the NKF and CCM groups. RESULTS: A total of 404 patients (NKF, n = 124; CCM, n = 280) with duodenal papillary tumors were included. The primary and overall cannulation rates were 92.1% (372/404) and 96.0% (388/404), respectively. Compared to CCMs, NKF was associated with a significantly higher successful cannulation rate (99.2% versus 88.9%, P < 0.001) and significantly lower cannulation times (2.1 ± 2.0 min versus 4.7 ± 5.2 min), procedure times (8.8 ± 3.8 min versus 12.9 ± 7.6 min), and unintentional pancreatic duct cannulation rates (1.6% versus 20%), with P < 0.001 for all. Overall adverse events occurred less frequently in the NKF group (3.2% versus 10.7%, P = 0.011). Of these adverse events, post-ERCP pancreatitis (PEP) was significantly lower in the NKF group than in the CCM group (1.6% versus 6.8%, P = 0.03). Bleeding and cholangitis rarely occurred with either cannulation method (0.8% versus 2.1%, P = 0.681, and 0.8% versus 1.7%, P = 0.671, respectively). CONCLUSION: NKF is a more effective and safer procedure than CCMs for patients with duodenal papillary tumors.

8.
ISME J ; 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33028975

RESUMO

Cropping systems have fertilized soils for decades with undetermined consequences for the productivity and functioning of terrestrial ecosystems. One of the critical unknowns is the role of soil biodiversity in controlling crop production after decades of fertilization. This knowledge gap limits our capacity to assess how changes in soil biodiversity could alter crop production and soil health in changing environments. Here, we used multitrophic ecological networks to investigate the importance of soil biodiversity, in particular, the biodiversity of key-stone taxa in controlling soil functioning and wheat production in a 35-year field fertilization experiment. We found strong and positive associations between soil functional genes, crop production and the biodiversity of key-stone phylotypes; soils supporting a larger number of key-stone nematode, bacteria and fungi phylotypes yielded the highest wheat production. These key-stone phylotypes were also positively associated with plant growth (phototrophic bacteria, nitrogen fixers) and multiple functional genes related to nutrient cycling. The retrieved information on the genomes clustered with key-stone bacterial phylotypes indicated that the key-stone taxa had higher gene copies of oxidoreductases (participating most biogeochemical cycles of ecosystems and linking to microbial energetics) and 71 essential functional genes associated with carbon, nitrogen, phosphorus, and sulfur cycling. Altogether, our work highlights the fundamental role of the biodiversity of key-stone phylotypes in maintaining soil functioning and crop production after several decades of fertilization, and provides a list of key-stone phylotypes linking to crop production and soil nutrient cycling, which could give science-based guidance for sustainable food production.

9.
Artigo em Inglês | MEDLINE | ID: mdl-33030686

RESUMO

PURPOSE: This meta-analysis compared the efficacy and safety of oral anticoagulation (OAC) therapy alone versus OAC plus single antiplatelet therapy (SAPT) in patients with an indication for chronic OAC (mostly due to atrial fibrillation) after transcatheter aortic valve implantation (TAVI). METHODS: A systematic literature search was performed in the PubMed, Embase, and Cochrane Library databases to identify relevant studies. Data was extracted from the eligible studies and outcomes expressed as relative risks (RRs) with 95% confidence intervals (CIs). RESULTS: Five studies comprising 1344 patients with an indication for chronic OAC and undergoing TAVI were included. Of the 1344 patients, 480 patients received OAC therapy alone and 864 patients received OAC plus SAPT. There were no significant differences between OAC alone versus OAC plus SAPT in all-cause mortality (RR = 1.05, 95% CI 0.84-1.30, p = 0.69) and ischemic stroke (RR = 0.95, 95% CI 0.95-1.61, p = 0.86). However, OAC alone was associated with significantly lower risks of all bleeding events (RR = 0.62, 95% CI 0.49-0.69, p < 0.0001) and major and/ life-threatening bleeding events (RR = 0.57, 95% CI 0.42-0.76, p = 0.0002) compared to OAC plus SAPT. CONCLUSION: In patients with an indication for chronic anticoagulation, post-TAVI antithrombotic therapy with OAC alone compared to OAC plus SAPT may be not significantly different in reducing all-cause mortality and ischemic stroke, but has an important benefit in a significantly lower risk of all bleeding and major and/life-threatening bleeding events.

11.
Sci Total Environ ; 755(Pt 2): 142702, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33049532

RESUMO

Environmental selection of antibiotic resistance genes (ARGs) is considered to be caused by antibiotic or metal residues, frequently used in livestock. In this study we examined three commercial poultry farms to correlate the co-occurrence patterns of antibiotic and metal residues to the presence of ARGs. We quantified 283 ARGs, 12 mobile genetic elements (MGEs), 49 targeted antibiotics, 7 heavy metals and sequenced 16S rRNA genes. The abundance and type of ARG were significantly enriched in manure while soil harbored the most diverse bacterial community. Procrustes analysis displayed significant correlations between ARGs/MGEs and the microbiome. Cadmium (Cd), arsenic (As), zinc (Zn), copper (Cu) and lead (Pb) were responsible for a majority of positive correlations to ARGs when compared to antibiotics. Integrons and transposons co-occurred with ARGs corresponding to 9 classes of antibiotics, especially Class1 integrase intI-1LC. Redundancy analysis (RDA) and Variance partitioning analysis (VPA) showed that antibiotics, metals, MGEs and bacteria explain solely 0.7%, 5.7%, 12.4%, and 21.9% of variances of ARGs in the microbial community, respectively. These results suggested that bacterial composition and horizontal gene transfer were the major factors shaping the composition of ARGs; Metals had a bigger effect on ARG profile than detected antibiotics in this study.

12.
BMC Med Inform Decis Mak ; 20(Suppl 9): 223, 2020 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-32967667

RESUMO

BACKGROUND: Prostate cancer is a very common and highly fatal in men. Current non-invasive detection methods like serum biomarker are unsatisfactory. Biomarkers with high accuracy for diagnostic of prostate cancer are urgently needed. Many lipid species have been found related to various cancers. The purpose of our study is to explore the diagnostic value of lipids for prostate cancer. RESULTS: Using triple quadruple liquid chromatography electrospray ionization tandem mass spectrometry, we performed lipidomics profiling of 367 lipids on a total 114 plasma samples from 30 patients with prostate cancer, 38 patients with benign prostatic hyperplasia (BPH), and 46 male healthy controls to evaluate the lipids as potential biomarkers in the diagnosis of prostate cancer. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database was used to construct the potential mechanism pathway. After statistical analysis, five lipids were identified as a panel of potential biomarkers for the detection of prostate cancer between prostate cancer group and the BPH group; the sensitivity, specificity, and area under curve (AUC) of the combination of these five lipids were 73.3, 81.6%, and 0.800, respectively. We also identified another panel of five lipids in distinguishing between prostate cancer group and the control group with predictive values of sensitivity at 76.7%, specificity at 80.4%, and AUC at 0.836, respectively. The glycerophospholipid metabolism pathway of the selected lipids was considered as the target pathway. CONCLUSIONS: Our study indicated that the identified plasma lipid biomarkers have potential in the diagnosis of prostate cancer.

13.
Sci Total Environ ; 752: 141874, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32889284

RESUMO

Soil fauna takes an active part in accelerating turnover of nutrients in terrestrial ecosystems. Anaerobic ammonium oxidation (anammox) has been widely characterized, however, whether anammox is active in earthworm gut and the effect of earthworm on anammox in soil remain unknown. In this study, the activity, abundance and community of anammox bacteria in earthworm guts and soils from microcosms were determined using a 15N-tracing technique, quantitative PCR, and anammox bacterial 16S rRNA gene amplicon sequencing. Results showed that anammox rates in guts ranged between 5.81 and 14.19 nmol N g-1 dw gut content h-1, which were significantly (P < 0.01) higher than that in their surrounding soils during 30 day incubation. On the contrary, abundances of hzsB genes encoding subunit B hydrazine synthase in guts were significantly (P < 0.05) lower than those in their surrounding soils. Anammox rates, denitrification N2 production rates and hzsB genes in soils with earthworms were significantly (P < 0.05) lower than those in control soils. Anammox bacterial compositions differed significantly (P < 0.05) between gut and soil, and earthworm altered anammox bacterial communities in soils. Brocadia, Kuenenia and abundant unclassified anammox bacteria were detected in collected soils and gut contents, in which Brocadia was only detected in guts. These results suggested that microbes in earthworm gut increase, but present of earthworm reduces anammox and denitrification associated N loss by altering the anammox bacterial community compositions in soils.

15.
ISME J ; 2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-32963346

RESUMO

Antibiotic-resistant pathogens pose a significant threat to human health. Several dispersal mechanisms have been described, but transport of both microbes and antibiotic resistance genes (ARGs) via atmospheric particles has received little attention as a pathway for global dissemination. These atmospheric particles can return to the Earth's surface via rain or snowfall, and thus promote long-distance spread of ARGs. However, the diversity and abundance of ARGs in fresh snow has not been studied and their potential correlation with particulate air pollution is not well explored. Here, we characterized ARGs in 44 samples of fresh snow from major cities in China, three in North America, and one in Europe, spanning a gradient from pristine to heavily anthropogenically influenced ecosystems. High-throughput qPCR analysis of ARGs and mobile genetic elements (MGEs) provided strong indications that dissemination of ARGs in fresh snow could be exacerbated by air pollution, severely increasing the health risks of both air pollution and ARGs. We showed that snowfall did effectively spread ARGs from point sources over the Earth surface. Together our findings urge for better pollution control to reduce the risk of global dissemination of antibiotic resistance genes.

16.
Int J Surg ; 83: 39-46, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32927138

RESUMO

OBJECTIVE: To evaluate the clinical efficacy of oblique lateral interbody fusion combined posterior percutaneous pedicle screw fixation in the treatment of single segment lumbar tuberculosis. METHODS: Patients who underwent surgical treatment for single segment lumbar tuberculosis from 2015 to 2018 in our department were retrospectively included in this study. The included patients were divided into two groups, namely oblique lateral interbody fusion combined percutaneous pedicle screw fixation (OLIF) group and traditional posterior transforaminal or transpedicular approach debridement and pedicle screws fixation (PTA) group, according to the surgical methods. Outcomes including operative time, operative blood loss, hospital stay, visual analogue scale (VAS) score, Oswestry disability index (ODI), erythrocyte sedimentation rate (ESR), C reactive protein (CRP), Cobb angle correction and loss, bone fusion time, ASIA grade and complications were all recorded and compared. RESULTS: A total of 60 patients were included in this study, involving 23 patients in the OLIF group and 37 patients in the PTA group. The OLIF group had less operative time, blood loss and shorter hospital stay compared with the PTA group (P < 0.05). Both the two groups achieved significant improvements in ESR, CRP and ASIA grade at the last follow-up (P < 0.05), but no significant differences were found between them (P>0.05). There were no significant differences in Cobb angle correction and loss between the two groups (P > 0.05), but the bone graft fusion time of the OLIF group was significantly shorter than the PTA group (P < 0.05). The two groups achieved similar improvement in VAS score and ODI at 12 months postoperative and the last follow-up, however, OLIF group had a lower VAS score and ODI at 1 month, 3 months and 6 months postoperative (P < 0.05). No significant difference was found in complications between the two groups (P > 0.05) and all patients were cured after active treatment. CONCLUSIONS: Both OLIF and PTA can achieve satisfactory clinical efficacy in the surgical treatment of single segment lumbar TB, but OLIF has the advantages of less surgical trauma, faster postoperative recovery and shorter bone fusion time.

17.
Medicine (Baltimore) ; 99(37): e22051, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32925738

RESUMO

Addressing pancreaticobiliary disorders concomitant with gastroesophageal varices remains challenging. The goal of this study was to evaluate and compare the efficacy and safety of endoscopic retrograde cholangiopancreatography (ERCP) in cirrhotic and noncirrhotic patients with gastroesophageal varices.We retrospectively analyzed the data of consecutive patients with gastroesophageal varices who underwent ERCP.Two hundred seventy ERCP procedures were performed on 208 patients. The overall technical success rate was 98.5%, and no difference was found between cirrhotic and noncirrhotic patients (98.7% vs 97.7%, P = .511); of these, endoscopic retrograde biliary drainage, endoscopic metal biliary endoprosthesis placement, endoscopic retrograde pancreatic drainage, and stone extraction were conducted in 173/270 (64.1%), 27/270 (10.0%), 26/270 (9.6%), and 116/270 (43.0%) cases, respectively. Endoscopic retrograde biliary drainage and stone extraction were more frequently performed in cirrhotic cases (67.7% versus 45.5%, P = .005; 46.5% versus 25.0%, P = .009, respectively), while the noncirrhotic group had significantly higher rates of endoscopic metal biliary endoprosthesis placement (31.8% versus 5.8%, P = .000) and endoscopic retrograde pancreatic drainage (18.2% versus 8.0%, P = .036) than the cirrhotic group. The overall rate of adverse events was 21.1%, including fever (6.7%), post-ERCP pancreatitis ( 3.0%), hyperamylasemia (6.3%), duodenal papilla bleeding (3.3%), cardiac mucosal laceration (1.1%), and perforation (0.4%). No differences in any of the adverse events were found between the 2 groups. Additionally, gastroesophageal variceal bleeding occurred in 1 patient with grade III varices 7 days after ERCP.ERCP may be effective and safe for patients with gastroesophageal varices, irrespective of the etiologies caused by liver cirrhosis.


Assuntos
Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Varizes Esofágicas e Gástricas/cirurgia , Cirrose Hepática/complicações , Adulto , Idoso , Varizes Esofágicas e Gástricas/etiologia , Feminino , Humanos , Hipertensão Portal/complicações , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Estudos Retrospectivos
18.
20.
Clin Respir J ; 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32935471

RESUMO

BACKGROUND: The feasibility of pneumothorax following low-dose CT-guided puncture lung biopsy in different severities of COPD has not been reported. METHODS: The data of the patients with pulmonary lesion who underwent low-dose CT-guided lung biopsy by one experienced operator in our hospital from January 1st to September 30th in 2019 were retrospectively collected. They were divided into COPD group and non-COPD group. The risk factors, incidence and severity of pneumothorax with the severity of COPD and changes in MMRC score, treatment way and discharge time after pneumothorax were assessed. RESULTS: Two hundred and nineteen patients were retrospectively enrolled in this study with 64 in the COPD group and 155 in the non-COPD group. The average age, MMRC score and the incidence of pneumothorax after biopsy were significantly higher in the COPD group (64.7 ± 1.27 years, 1.02 ± 0.13, 31.3%) than in the non-COPD group (58.8 ± 1.16 years, 0.35 ± 0.06, 17.4%, P < 0.05). The incidence of pneumothorax between I-II and III-IV in COPD did not reach the significant difference (P = 0.863). COPD was the only independent risk factor for pneumothorax after biopsy in a multivariable regression (P < 0.05). MMRC score was significantly increased at post-pneumothorax in the two groups (P < 0.001). There was no significant difference in diagnostic rate, severity of pneumothorax, the proportion of delayed pneumothorax, the changes in treatment way and discharge time between the two groups (P > 0.05). CONCLUSION: Although the incidence of pneumothorax after low dose CT-guided lung biopsy is increased in COPD, there was no difference in the severity of pneumothorax amongst the different severities of COPD and it is well-tolerated without increasing medical burden.

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