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1.
Sci Total Environ ; 771: 144839, 2021 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-33545462

RESUMO

3-methylcholanthrene (3-MCA) is a typical representative PAH. It has strong toxicity and is a typical chemical carcinogen. However, the epigenetic mechanisms underlying 3-MCA-induced tumourigenesis are largely unknown. In this study, a model of the 3-MCA-induced malignant transformation of human bronchial epithelial (HBE) cells was established successfully. The profiles of gene expression and DNA methylation and hydroxymethylation were obtained and analysed with an Illumina HiSeq 4000. A total of 707 genes were found to be significantly up-regulated, and 686 genes were found to be significantly down-regulated. Compared to control cells, 8545 mRNA-associated differentially methylated regions and 15,121 mRNA-associated differentially hydroxymethylated regions in promoters were found to be significantly altered in transformed cells. By using mRNA expression and DNA methylation and hydroxymethylation interaction analysis, 99 differentially expressed genes were identified. Among them, CA9 and EGLN3 were verified to be significantly down-regulated, and CARD6 and LCP1 were shown to be significantly up-regulated, and these genes mainly participated in cell growth, migration and invasion, indicating that these genes were key genes involved in the 3-MCA-induced malignant transformation of HBE cells. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that a large number of differentially expressed genes (DEGs) were involved mainly in RNA polymerase II transcription factor activity, chemical carcinogenesis, base-excision repair (BER), cytokine-cytokine receptor interactions, glycerolipid metabolism, steroid hormone biosynthesis, cAMP signalling pathways and other signalling pathways. Our study suggested that characteristic gene alterations associated with DNA methylation and hydroxymethylation could play important roles in environmental 3-MCA-induced lung carcinogenesis.

2.
Proc Natl Acad Sci U S A ; 118(8)2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33558418

RESUMO

The expansion of anatomically modern humans (AMHs) from Africa around 65,000 to 45,000 y ago (ca. 65 to 45 ka) led to the establishment of present-day non-African populations. Some paleoanthropologists have argued that fossil discoveries from Huanglong, Zhiren, Luna, and Fuyan caves in southern China indicate one or more prior dispersals, perhaps as early as ca. 120 ka. We investigated the age of the human remains from three of these localities and two additional early AMH sites (Yangjiapo and Sanyou caves, Hubei) by combining ancient DNA (aDNA) analysis with a multimethod geological dating strategy. Although U-Th dating of capping flowstones suggested they lie within the range ca. 168 to 70 ka, analyses of aDNA and direct AMS 14C dating on human teeth from Fuyan and Yangjiapo caves showed they derive from the Holocene. OSL dating of sediments and AMS 14C analysis of mammal teeth and charcoal also demonstrated major discrepancies from the flowstone ages; the difference between them being an order of magnitude or more at most of these localities. Our work highlights the surprisingly complex depositional history recorded at these subtropical caves which involved one or more episodes of erosion and redeposition or intrusion as recently as the late Holocene. In light of our findings, the first appearance datum for AMHs in southern China should probably lie within the timeframe set by molecular data of ca. 50 to 45 ka.

3.
J Magn Reson Imaging ; 2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33594768

RESUMO

BACKGROUND: Magnetic resonance imaging (MRI)-based radiomics features (RFs) quantify tumors radiological phenotypes but are sensitive to postprocessing parameters, including the intensity harmonization technique (IHT), while mappings enable objective quantitative assessment. PURPOSE: To investigate whether T2 mapping could improve repeatability, reproducibility, and performances of radiomics compared to conventional T2-weighted imaging (T2WI). STUDY TYPE: Prospective. SUBJECTS: Twenty-six healthy adults. FIELD STRENGTH/SEQUENCE: Respiratory-trigged radial turbo spin echo (TSE) multiecho T2 mapping (prototype) and conventional TSE T2WI of the abdomen were acquired twice at 1.5 T. ASSESSMENT: T2 maps were reconstructed using a two-parameter exponential fitting model. Volumes-of-interest (VOIs) were manually drawn in six tissues: liver, kidney, pancreas, muscle, bone, and spleen. After co-registration, conventional T2WIs were processed with two IHTs (standardization [std] and histogram-matching [HM]) resulting in four paired input image types: initial T2WI, T2WIstd , T2WIHM , and T2-map. VOIs were propagated to extract 45 RFs from MRI-1 and MRI-2 of each image type (LIFEx, v5.10). STATISTICAL TESTS: Influence of the input data type on RF values was evaluated with analysis of variance. RFs test-retest repeatability and reproducibility over multiple segmentations were evaluated with intra-class correlation coefficient (ICC). Correlations between k-means clusters and the six tissues depending on the RFs dataset were investigated with adjusted-Rand-index (ARI). RESULTS: About 41 of 45 (91.1%) RFs were significantly influenced by the input image type (P values < 0.05), which was the most influential factor on repeatability of RFs (P-value < 0.05). Repeatability ICCs from T2-map displayed intermediate values between the initial T2WI (range: 0.407-0.736) and the T2WIHM (range: 0.724-0.817). The number of RFs with interobserver and intraobserver reproducibility ICCs ≥ 0.90 was 37/45 (82.2%) for T2WIHM , 33/45 (73.3%) for T2WIstd , 31/45 (68.9%) for T2 map, and 25/45 (55.6%) for the initial T2WI. T2 map provided the best tissue discrimination (ARI = 0.414 vs. 0.157 with T2WIHM ). DATA CONCLUSION: T2 mapping provided RFs with moderate to substantial repeatability and reproducibility ICCs, along with the most preserved discriminative information. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: 1.

4.
Lupus Sci Med ; 8(1)2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33558437

RESUMO

OBJECTIVE: To evaluate the performance of the European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) SLE classification criteria in a cohort of patients with biopsy-confirmed lupus nephritis (LN) and their renal prognosis. METHODS: Patients with newly diagnosed SLE attending and followed up for >12 months were included. A retrospective review of all patients with renal biopsy fulfilling a consensus expert opinion during 2014 and 2018. Clinical, serological and pathological data were collected and each patient was assigned a high/low criteria scores (HS/LS) group. Survival curves for flare adjusted for multiplicity on renal flares, was applied to the two groups. RESULTS: Applying EULAR/ACR criteria in our cohort of 126 patients, 6 (4.76%) did not meet the criterion, resulting in a sensitivity of 95.24%. The EULAR/ACR criteria scores was positively correlated with SLE disease activity index scores. Additionally, we noticed that a significant difference in clinical and immunological manifestations between HS and LS group. We observed a higher proportions of class Ⅲ or Ⅳ LN and lower proportions of class Ⅱ or V LN (p=0.034) and pathological higher activity index in HS group (p=0.007). Compared with LS groups, patients involved more severe renal damage and achieved higher rate of complete remission in the HS group. The Kaplan-Meier exploratory analyses, adjusted for LN classification, estimated glomerular filtration rate, activity index and chronicity index and induction and maintenance treatments, showed that patients in the HS group had a tendency of higher renal flare risk than that in the LS group (HR=0.21, p=0.04). CONCLUSIONS: The EULAR/ACR criteria performed high sensitivity in identifying SLE in this cohort of biopsy-confirmed LN. Patients with LN with high criteria scores had more extrarenal manifestations, and worse renal prognosis in the short and long terms.

5.
Int J Biol Sci ; 17(2): 487-497, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33613107

RESUMO

Background: This meta-analysis was aimed to quantitatively assess the associations of metabolic syndrome (MetS) and its components with colorectal cancer (CRC). Methods: PubMed, EMBASE and Web of Science databases were systematically searched for eligible studies. A total of 18 studies for CRC incidence and 12 studies for CRC mortality were identified. Results: MetS was associated with an increased risk of CRC incidence and mortality in male (RR: 1.28, 95 % CI 1.16-1.39, and 1.24, 1.18-1.31, respectively) and correlated with an increased risk of CRC incidence in female (RR: 1.21, 1.13-1.30), but not with CRC mortality in female. MetS increased the risk of cancer-specific mortality (RR: 1.72, 1.03-2.42), but not overall mortality. The risk estimates of CRC incidence changed little depending on age, sex, cancer site, the type of studies, ethnicity, publication year, or definition of MetS. As for CRC mortality, further stratified analyses indicated statistical significance in studies with assessing cancer-specific survival outcome, in male, a cohort design, ethnicity of non-Chinese or with definition of MetS as ≥ 3 metabolic abnormalities. Obesity and hyperglycemia are risk factors of CRC incidence in both male and female. Only dysglycemia is the risk factor for CRC mortality. Conclusions: MetS is associated with an increased risk of CRC incidence and cancer-specific mortality, but not overall mortality. In addition, MetS may increase the CRC mortality in male rather than in female. However, since most of the studies on CRC mortality were conducted in Chinese, further studies are needed to clarify this connection.

6.
J Alzheimers Dis ; 2021 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-33579854

RESUMO

BACKGROUND: Mechanisms through which arterial stiffness impacts cognitive function are crucial for devising better strategies to prevent cognitive decline. OBJECTIVE: To examine the associations of arterial stiffness with white matter integrity and cognition in community dwellings, and to investigate whether white matter injury was the intermediate of the associations between arterial stiffness and cognition. METHODS: This study was a cross-sectional analysis on 952 subjects (aged 55.5±9.1 years) who underwent diffusion tensor imaging and measurement of brachial-ankle pulse wave velocity (baPWV). Both linear regression and tract-based spatial statistics were used to investigate the association between baPWV and white matter integrity. The association between baPWV and global cognitive function, measured as the mini-mental state examination (MMSE) was evaluated. Mediation analysis was performed to assess the influence of white matter integrity on the association of baPWV with MMSE. RESULTS: Increased baPWV was significantly associated with lower mean global fractional anisotropy (ß= -0.118, p <  0.001), higher mean diffusivity (ß= 0.161, p <  0.001), axial diffusivity (ß= 0.160, p <  0.001), and radial diffusivity (ß= 0.147, p <  0.001) after adjustment of age, sex, and hypertension, which were measures having a direct effect on arterial stiffness and white matter integrity. After adjustment of age, sex, education, apolipoprotein E ɛ4, cardiovascular risk factors, and brain atrophy, we found an association of increased baPWV with worse performance on MMSE (ß= -0.093, p = 0.011). White matter disruption partially mediated the effect of baPWV on MMSE. CONCLUSION: Arterial stiffness is associated with white matter disruption and cognitive decline. Reduced white matter integrity partially explained the effect of arterial stiffness on cognition.

7.
Anticancer Drugs ; 2021 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-33587353

RESUMO

BACKGROUND: MiRNA is an important regulator of tumorigenesis and tumor progression. MiR-337 expression was increased in pancreatic cancer tissues and it was associated with patients' survival. This study aimed to explore the influence and the potential working mechanism of miR-337 on the malignant behaviors of pancreatic cancer cells. METHODS: MiR-337 expression was detected by qRT-PCR. The expression levels of STAT3, epithelial-mesenchymal transition-related genes and Wnt/ß-Catenin pathway genes were evaluated by qRT-PCR and western blot. Cell counting kit -8 and colony formation assays were conducted to examine the proliferation of AsPC-1 and SW1990 cells. Wound healing and transwell assays were performed to determine the migration and invasion of AsPC-1 and SW1990 cells. The predicted target gene of miR-337 was verified by luciferase reporter assay. RESULTS: The expression of miR-337 was decreased and STAT3 expression was increased in pancreatic cancer tissues as well as tumor cells. Overexpression of miR-337 suppressed proliferation, invasion and migration of AsPC-1 and SW1990 cells. MiR-337 targeted 3'UTR of STAT3 and inhibited STAT3 expression. In addition, exogenous STAT3 partially restored the inhibitory role of miR-337 on proliferation, invasion and migration of AsPC-1 and SW1990 cells. Moreover, miR-337 impeded the expression of Wnt/ß-catenin pathway-related genes. Through the saving experiment, we found that the inhibitory effect of miR-337 on AsPC-1 and SW1990 cells was abolished by the addition of LiCl. CONCLUSION: These outcomes expounded that miR-337 inactivated the Wnt/ß-catenin pathway to suppress the malignant behaviors of pancreatic cancer cells through targeting STAT3. This study may provide a novel biomarker for diagnosis and a new therapeutic target for pancreatic cancer treatment.

8.
Phytother Res ; 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33452698

RESUMO

The present study was undertaken to identify whether prostaglandin E2 receptor is the potential receptor/binding site for Ginkgolide A, Ginkgolide B, Ginkgolide K, and Bilobalide, the four main ingredients of the Ginkgo biloba L., leaves. Using functional assays, we identified EP4, coupled with Gs protein, as a target of Ginkgolide B. In human neuroblastoma SH-SY5Y cells suffered from oxygen-glucose deprivation/reperfusion, Ginkgolide B-activated PKA, Akt, and ERK1/2 as well as Src-mediated transactivation of epidermal growth factor receptor. These resulted in downstream signaling pathways, which enhanced cell survival and inhibited apoptosis. Knockdown of EP4 prevented Ginkgolide B-mediated Src, epidermal growth factor receptor (EGFR), Akt, and ERK1/2 phosphorylation and neuroprotective effects. Moreover, Src inhibitor prevented Ginkgolide B-mediated EGFR transactivation and the downstream Akt and ERK1/2 activation, while the phosphorylation of PKA induced by Ginkgolide B was not affected, indicating Ginkgolide B might transactivate EGFR in a ligand-independent manner. EP4 knockdown in a rat middle cerebral artery occlusion (MCAO) model prevented Ginkgolide B-mediated infarct size reduction and neurological assessment improvement. At the same time, the increased expressions of p-Akt, p-ERK1/2, p-PKA, p-Src, and p-EGFR and the deceased expression of cleaved capases-3 induced by Ginkgolide B in cerebral cortex were blocked due to EP4 knockdown. In conclusion, Ginkgolide B exerts neuroprotective effects in rat MCAO model through the activation of EP4 and the downstream transactivation of EGFR.

9.
BMC Med Inform Decis Mak ; 21(1): 19, 2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33446198

RESUMO

BACKGROUND: CPGs are not uniformly successful in improving care and several instances of implementation failure have been reported. Performing a comprehensive assessment of the barriers and enablers is key to developing an informed implementation strategy. Our objective was to investigate determinants of guideline implementation and explore associations of self-reported adherence to guidelines with characteristics of participants in China. METHODS: This is a cross-sectional survey, using multi-stage stratified typical sampling based on China's economic regional divisions (the East, the Middle, the West and the Northeast). 2-5 provinces were selected from each region. 2-3 cities were selected in each province, and secondary and tertiary hospitals from each city were included. We developed a questionnaire underpinned by recommended methods for the design and conduct of self-administered surveys and based on conceptual framework of guideline use, in-depth related literature analysis, guideline development manuals, related behavior change theory. Finally, multivariate analyses were performed using logistic regression to produce adjusted odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS: The questionnaire consisted of four sections: knowledge of methodology for developing guidelines; barriers to accessing guideline; barriers to guideline implementation; and methods for improving guideline implementation. There were 1732 participants (87.3% response rate) from 51 hospitals. Of these, 77.2% reported to have used guidelines frequently or very frequently. The key barriers to guideline use were lack of education or training (46.2%), and overly simplistic wording or overly broad scope of recommendations (43.8%). Level of adherence to guidelines was associated with geographical regions (the northeast P < 0.001; the west P = 0.02; the middle P < 0.001 compared with the east), hospital grades (P = 0.028), length of practitioners' practice (P = 0.006), education background (Ph.D., P = 0.027; Master, P = 0.002), evidence-based medicine skills acquired in work unit (P = 0.012), and medical specialty of practitioner (General Practice, P = 0.006; Surgery, P = 0.043). CONCLUSION: Despite general acknowledgement of the importance of guidelines, the use of guidelines was not as frequent as might have been expected. To optimize the likelihood of adherence to guidelines, guideline implementation should follow an actively developed dissemination plan incorporating features associated with adherence in our study.

10.
J Chromatogr Sci ; 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33434918

RESUMO

A bioanalytical method for simultaneous quantification of isoniazid (INH), pyrazinamide (PZA) and ethambutol (EMB) in plasma was developed and validated using high-performance liquid chromatography with tandem mass spectrometry. After extracted by protein precipitation with acetonitrile, the analytes were separated on a Waters XBridge Amide column by isocratic elution with acetonitrile and 5 mM ammonium acetate solution containing 0.3% formic acid (77:23, v/v) at a flow rate of 0.5 mL/min. The detection was carried out on a triple quadrupole tandem mass spectrometer equipped with an electrospray ionization source in positive mode by monitoring the selected ion transitions at m/z 205.2 â†’ 116.1, m/z 137.9 â†’ 121.2, m/z 124.3 â†’ 78.9 and m/z 213.1 â†’ 122.4 for EMB, INH, PZA and EMB-d8 Internal standard (IS), respectively. The calibration curves were linear over the range of 0.0125-2.00 µg/mL for EMB, 0.0625-10.0 µg/mL for INH and 0.250-40.0 µg/mL for PZA. Neither cross-analytes inter-conversion nor matrix effects were observed. The intra- and inter-assay precision (%RSD) values were within 8.80%, and accuracy (%RE) ranged from -11.13 to 13.49%, indicating that the precision and accuracy were well within the acceptable limits of variation. The method would be helpful for analysis of EMB, INH and PZA in plasma samples from clinical pharmacokinetics and therapeutic drug monitoring.

11.
Cell Tissue Res ; 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33439348

RESUMO

Organ preservation is a prerequisite for an urgent increase in the availability of organs for solid organ transplantation (SOT). An increasing amount of expanded criteria donor (ECD) organs are used clinically. Currently, the paradigm of organ preservation is shifting from simple reduction of cellular metabolic activity to maximal simulation of an ex vivo physiological microenvironment. An ideal organ preservation technique should not only preserve isolated organs but also offer the possibility of rehabilitation and evaluation of organ function prior to transplantation. Based on the fact that mesenchymal stromal cells (MSCs) possess strong regeneration properties, the combination of MSCs with machine perfusion (MP) is expected to be superior to conventional preservation methods. In recent years, several studies have attempted to use this strategy for SOT showing promising outcomes. With better organ function during ex vivo preservation and the potential of utilization of organs previously deemed untransplantable, this strategy is meaningful for patients with organ failure to help overcome organ shortage in the field of SOT.

12.
Sci China Life Sci ; 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33439457

RESUMO

We aimed to assess the associations of large artery stenosis (LAS) and cerebral small vessel disease (CSVD) with the risk of ischemic stroke and to investigate their respective and combined contributions. In the prospective population-based Shunyi Study, 1,082 stroke-free participants aged 55.9±9.1 years were included. Participants were followed for incident stroke throughout the study period (2013-2019). Total small vessel disease score was used to measure CSVD burden. Cervico-cerebral large artery stenosis was evaluated via brain magnetic resonance angiography and carotid ultrasound. We estimated the risk of ischemic stroke in relation to LAS and CSVD with Cox regression models. During a mean follow-up of 4.2 years, 34 participants (3.1%) experienced at least one ischemic stroke. Severe LAS (≥50% stenosis versus no stenosis: HR=3.27 (95% CI: 1.31-8.18)) and high CSVD burden (total small vessel disease score 2-4 versus 0 point: HR=12.73 (4.83-33.53)) were associated with increased stroke risk independently. In multivariate models, CSVD burden (7.72%) explained a larger portion of the variation in stroke risk than severity of LAS (3.49%). Our findings identified that both LAS and CSVD were associated with future ischemic stroke in asymptomatic subjects, while those with high CSVD burden deserve more attention in primary prevention of stroke.

13.
Int Urol Nephrol ; 2021 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-33392885

RESUMO

PURPOSE: This study evaluated the correlation of anti-ß2-glycoprotein I (anti-ß2-GPI) antibodies with complement activation in patients with idiopathic membranous nephropathy (IMN). METHODS: Thirty-two IMN patients with positive anti-ß2-GPI antibody were enrolled, and 32 age- and sex-matched IMN patients with negative anti-ß2-GPI antibody were randomly enrolled as controls. The frozen serum samples of these 64 patients were collected for detection of anti-phospholipase A2 receptor (PLA2R) antibody and the activity of three complement pathways. Paraffin specimens of the kidney tissues of these 64 patients were collected for immunohistochemical staining of C4d. RESULTS: IMN patients with positive anti-ß2-GPI antibody had a significant decline of the residual complement activity of alternative pathway than those with negative anti-ß2-GPI antibody (37.4 ± 21.2% vs 65.7 ± 50.5%, P = 0.021). The positive rate of kidney C4d staining in IMN patients with and without anti-ß2-GPI was 65.6 and 81.2%, with no significant difference (P = 0.257). Patients with and without anti-ß2-GPI had the same positive rate of anti-PLA2R antibody. CONCLUSION: Anti-ß2-GPI antibody was associated with alternative complement activation in patients with IMN.

14.
Neurochem Res ; 46(3): 660-674, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33392910

RESUMO

Depression afflicts more than 300 million people worldwide, but there is currently no universally effective drug in clinical practice. In this study, chronic restraint stress (CRS)-induced mice depression model was used to study the antidepressant effects of resveratrol and its mechanism. Our results showed that resveratrol significantly attenuated depression-like behavior in mice. Consistent with behavioral changes, resveratrol significantly attenuated CRS-induced reduction in the density of dendrites and dendritic spines in both hippocampus and medial prefrontal cortex (mPFC). Meanwhile, in hippocampus and mPFC, resveratrol consistently alleviated CRS-induced cofilin1 activation by increasing its ser3 phosphorylation. In addition, cofilin1 immunofluorescence distribution in neuronal inner peri-membrane in controls, and cofilin1 diffusely distribution in the cytoplasm in CRS group were common in hippocampus. However, the distribution of cofilin1 in mPFC was reversed. Pearson's correlation analysis revealed that there was a significant positive correlation found between the sucrose consumption in sucrose preference test and the dendrite density in multiple sub-regions of hippocampus and mPFC, and a significant negative correlation between the immobility time in tail suspension test and the dendrite/dendritic spine density in several different areas of hippocampus and mPFC. P-cofilin1 was significantly positively correlated with the overall dendritic spine density in mPFC as well as with the overall dendrite density or BDNF in the hippocampus. Our results suggest that the BDNF/cofilin1 pathway, in which cofilin1 may be activated in a brain-specific manner, was involved in resveratrol's attenuating the dendrite and dendritic spine loss and behavioral abnormality.

15.
ACS Biomater Sci Eng ; 7(1): 133-143, 2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33332969

RESUMO

Artificial ligaments prepared from polyethylene terephthalate (PET) are widely accepted for clinical anterior cruciate ligament (ACL) reconstruction to recover the native function of knee joints. However, due to the chemical inertness and hydrophobicity of PET, improving its bioactivity and promoting graft-bone integration are still great challenges. Inspired by the natural biomineralization process on the surface of a historical stone, in this study, a bioactive organic/inorganic composite coating that is composed of poly(allylamine hydrochloride) and chondroitin sulfate with magnesium silicate (MgSiO3) doping is developed for surface modification of PET (MSPC-PET). This composite coating promotes adhesion and proliferation of bone marrow mesenchymal stem cells (BMSCs) and its bioactive inorganic components (MgSiO3) could induce osteogenic differentiation of BMSCs. Furthermore, an in vivo experiment indicated that this composite coating might afford superior graft-bone integration between MSPC-PET and the host bone tunnel, and fibrous scar tissue formation was also inhibited. More importantly, a biomechanical analysis proved that there was a strong integration between the MSPC-PET graft and the bone tunnel, which will improve biomechanical properties for the restoration of ACL function. This study shows that this bioactive composite coating-modified PET graft for the ACL reconstruction can effectively achieve good integration of ACL artificial grafts and bone tunnels and prevent surgical failure.

16.
Nat Commun ; 11(1): 6167, 2020 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-33268778

RESUMO

Thermoelectrics are promising by directly generating electricity from waste heat. However, (sub-)room-temperature thermoelectrics have been a long-standing challenge due to vanishing electronic entropy at low temperatures. Topological materials offer a new avenue for energy harvesting applications. Recent theories predicted that topological semimetals at the quantum limit can lead to a large, non-saturating thermopower and a quantized thermoelectric Hall conductivity approaching a universal value. Here, we experimentally demonstrate the non-saturating thermopower and quantized thermoelectric Hall effect in the topological Weyl semimetal (WSM) tantalum phosphide (TaP). An ultrahigh longitudinal thermopower [Formula: see text] and giant power factor [Formula: see text] are observed at ~40 K, which is largely attributed to the quantized thermoelectric Hall effect. Our work highlights the unique quantized thermoelectric Hall effect realized in a WSM toward low-temperature energy harvesting applications.

17.
Nutrients ; 12(12)2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33333894

RESUMO

Values for the digestible indispensable amino acid score (DIAAS) of a protein are based on true ileal amino acid (AA) digestibility values obtained in adult humans or in the growing pig as an animal model. An experiment was conducted using growing pigs to determine the true ileal digestibility (TID) values of AA in six cooked Chinese pulses (kidney bean, mung bean, adzuki bean, broad beans, peas and chickpeas). Each pulse was included in a diet as the only source of crude protein (CP). An N-free diet was given to allow determination of gut endogenous AA losses. Seven growing pigs each fitted with a T-cannula at the terminal ileum were allotted to a 7 by 6 incomplete Latin square with seven diets and six 7-d periods. The true digestibility values % for the total indispensable AA were higher (p < 0.001) for broad beans (87.3 ± 2.98) and lower (p < 0.001) for kidney bean (73.3 ± 4.84) than for the other pulses. For the older child (over 3 years), adolescent and adult, the DIAAS (%) was 88 for kidney bean, 86 for mung bean, 76 for chickpeas, 68 for peas, 64 for adzuki bean and 60 for broad beans.

18.
Aging (Albany NY) ; 122020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33226960

RESUMO

Autophagy is involved in degenerative diseases such as osteoarthritis and disc degeneration. Although, tumor necrosis factor α-induced protein 3 (TNFAIP3) is well-known as a key regulator of inflammation and autophagy, it is still not clear whether TNFAIP3 regulates autophagy to protect from human disc cells degeneration. We hypothesize that TNFAIP3 may also regulate autophagy to inhibit pro-inflammatory cytokines expression in human nucleus pulposus cells (NPCs). In this study, TNFAIP3 expression was increased in degenerative disc tissue as well as LPS-stimulated human NPCs, and the effect of TNFAIP3 in LPS-induced NPCs was further explored. The results demonstrated that pro-inflammatory cytokines expression in TNFAIP3-His cells was decreased, while it was increased in TNFAIP3-siRNA cells. Further molecular mechanism research showed that TNFAIP3-siRNA cells enhanced the phosphorylation of mammalian target of rapamycin (mTOR) and inhibited autophagy. Meanwhile, after treatment of TNFAIP3-siRNA cells with the mTOR inhibitor Torin1, the level of autophagy increased and the decrease of extracellular matrix was reversed. In summary, overexpressed TNFAIP3 can promote autophagy and reduce inflammation in LPS-induced human NPCs. Moreover, autophagy triggered by TNFAIP3 can ameliorate the degeneration of inflammatory human NPCs, providing a potential and an attractive therapeutic strategy for degenerative disease.

19.
Artigo em Inglês | MEDLINE | ID: mdl-33191586

RESUMO

By manipulating the nucleation and growth of solid materials, the synthesis of various sophisticated nanostructures has been achieved. Similar methodology, if applied to liquid, could enable the mass-production and control of ultra-small droplets at the scale of nanoparticles (10 -18  L or below). It would be highly desirable since droplets plays a fundamental role in numerous applications. Here we present a general strategy to synthesize and manipulate nanoscale droplets, similar to what has been done to solid nanoparticles in the classis solution-synthesis. It was achieved by a solute-induced phase separation which initiates the nucleation of droplets from a homogeneous solution. These liquid nanoparticles have great potentials to be manipulated like their solid counterparts, borrowing from the vast methodologies of nanoparticle synthesis, such as burst nucleation, seeded growth and co-precipitations. LNPs also serve as a general synthetic platform, to fabricate nanoreactors, drug-loaded carriers, and other hollow nanostructures with a variety of shell materials.

20.
Artigo em Inglês | MEDLINE | ID: mdl-33141329

RESUMO

OBJECTIVE: Rate-limiting enzyme 3b-hydroxysteroid dehydrogenase type 1 (3ßHSD1) encoded by HSD3B1 catalyzes the transition of dehydroepiandrosterone (DHEA) to dihydrotestosterone (DHT). The HSD3B1 (1245C) variant renders 3bHSD1 of resistant to ubiquitination and degradation, leading to a large amount of protein accumulation in the cell. Multiple clinical studies have shown that this mutation was correlated with resistance to androgen-deprivation therapy in prostate cancer. However, the results were not consistent depending on different treatment strategy and in some researches, the number of observed cases was relatively small. METHODS: To determine the effects of HSD3B1 (1245C) variant on resistance to androgen-deprivation therapy in prostate cancer, we performed a meta-analysis of the available literature. Electronic database searches identified appropriately designed studies that detected HSD3B1 in prostate cancer. We conducted a systematic search of studies in the following databases: PubMed, and EMBASE published until August 10, 2020 using the following search terms: (HSD3B1 AND ((((prostate cancer) OR prostatic neoplasm) OR prostatic carcinoma) OR prostatic cancer). RESULTS: Eight researches were included in this research. The result validated that the HSD3B1 (1245C) variant allele was associated with a shorter PFS (HR, 1.97; 95% CI, 1.39-2.79; P = 0.0001) (homozygous wild-type group) in men with prostate cancer when treated with ADT, however, a higher PFS (HR, 0.68; 95% CI, 0.48-0.96; P = 0.03) when treated with ADT and CYP17A1 inhibitor. CONCLUSION: The HSD3B1 (1245C) variant is a predictor of ADT plus CYP17A1 inhibitor response in prostate cancer.

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