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1.
Sci Immunol ; 4(41)2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31784498

RESUMO

Pathogenic CARD11 mutations cause aberrant nuclear factor κB (NF-κB) activation, which is presumably responsible for multiple immunological disorders. However, whether there is an NF-κB-independent regulatory mechanism contributing to CARD11 mutations related to pathogenesis remains undefined. Using three distinct genetic mouse models, the Card11 knockout (KO) mouse model mimicking primary immunodeficiency, the CARD11 E134G point mutation mouse model representing BENTA (B cell expansion with NF-κB and T cell anergy) disease, and the mouse model bearing oncogenic K215M mutation, we show that CARD11 has a noncanonical function as a negative regulator of the AKT-FOXO1 signal axis, independent of NF-κB activation. Although BENTA disease-related E134G mutant elevates NF-κB activation, we find that E134G mutant mice phenotypically copy Card11 KO mice, in which NF-κB activation is disrupted. Mechanistically, the E134G mutant causes exacerbated AKT activation and reduced FOXO1 protein in B cells similar to that in Card11 KO cells. Moreover, the oncogenic CARD11 mutant K215M reinforces the importance of the noncanonical function of CARD11. In contrast to the E134G mutant, K215M shows a stronger inhibitory effect on AKT activation and more stabilized FOXO1. Likewise, E134G and K215M mutants have converse impacts on B cell development and differentiation. Our results demonstrate that, besides NF-κB, CARD11 also governs the AKT/FOXO1 signaling pathway in B cells. The critical role of CARD11 is further revealed by the effects of pathogenic CARD11 mutants on this noncanonical regulatory function on the AKT-FOXO1 signaling axis.

2.
Genome Biol ; 20(1): 262, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31791371

RESUMO

BACKGROUND: Regulation of the mRNA life cycle is central to gene expression control and determination of cell fate. miRNAs represent a critical mRNA regulatory mechanism, but despite decades of research, their mode of action is still not fully understood. RESULTS: Here, we show that eIF4A2 is a major effector of the repressive miRNA pathway functioning via the Ccr4-Not complex. We demonstrate that while DDX6 interacts with Ccr4-Not, its effects in the mechanism are not as pronounced. Through its interaction with the Ccr4-Not complex, eIF4A2 represses mRNAs at translation initiation. We show evidence that native eIF4A2 has similar RNA selectivity to chemically inhibited eIF4A1. eIF4A2 exerts its repressive effect by binding purine-rich motifs which are enriched in the 5'UTR of target mRNAs directly upstream of the AUG start codon. CONCLUSIONS: Our data support a model whereby purine motifs towards the 3' end of the 5'UTR are associated with increased ribosome occupancy and possible uORF activation upon eIF4A2 binding.

3.
Geriatr Gerontol Int ; 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31803998

RESUMO

AIM: It is forecasted that the figure of families in China who lost their only child will reach 10 million by 2035. Traditional Chinese culture places these families in a particularly disadvantaged position for elderly care. It is quite important to understand the elderly care needs of the parents. METHODS: The cluster sampling method was used to select the parents who lost their only child in Wuhu city, China. Univariate and multivariate logistic regression analysis models were carried out to analyze factors influencing the parents' preferences for elderly care mode and choice of caregivers. RESULTS: The Geriatric Depression Scale score (P < 0.001) was significantly associated with the parents' preferences for elderly care mode. Parents with different sex, marital status and grandchildren status had different preferences for their choice of caregivers. The number of chronic diseases and Geriatric Depression Scale scores were significantly associated with preferences for choice of caregivers. CONCLUSIONS: These parents should have a preferential policy of check in to a nursing home and simplify the check-in procedure. The parents should receive prompt for depression and stay in the community for elderly care. The government should guarantee that spouseless parents have priority in enjoying nurse/nursing home worker services. The government should support the development of volunteer services. Geriatr Gerontol Int 2019; ••: ••-••.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31698523

RESUMO

BACKGROUND: This paper was carried out based on two motivations: (a) prior studies achieved mixed results regarding the effect of passive smoking on depression; and (b) studies on the impacts of passive smoking usually neglect effects on older people. In our paper, we studied the causal effect of passive smoking at home on depression among older people aged 60 years and older in China with a longitudinal study. METHODS: In assessing the causal relationship, we developed a fixed-effects instrumental variable method using an exogenous variable-health consciousness and the smoking status of parents-as instruments of smoking status. We used data from the China Health and Retirement Longitudinal Study (CHARLS), which provides a national, high-quality, and longitudinal household survey of people aged 45 years and older. RESULTS: Our empirical results reveal that passive smoking at home increased the depressive symptoms of older people, regardless of their smoking status. Moreover, the impact of passive smoking on depression is larger for nonsmokers than smokers. Additionally, the health consciousness and smoking status of parents are effective instrumental variables. CONCLUSIONS: This paper calls for governments and medical institutions to pay more attention to the health of older people and their need for healthy living environments.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31725399

RESUMO

Sample balancing includes sample selection and sample reweighting. Sample selection aims to remove some bad samples that may lead to bad local optima. Sample reweighting aims to assign optimal weights to samples to improve performance. In this article, we integrate a sample selection method based on self-paced learning into deep learning frameworks and study the influence of different sample selection strategies on training deep networks. In addition, most of the existing sample reweighting methods mainly take per-class sample number as a metric, which does not fully consider sample qualities. To improve the performance, we propose a novel metric based on the multiview semantic encoders to reweight the samples more appropriately. Then, we propose an optimization mechanism to embed sample weights into loss functions of deep networks, which can be trained in end-to-end manners. We conduct experiments on the CIFAR data set and the ImageNet data set. The experimental results demonstrate that our proposed sample balancing method can improve the performances of deep learning methods in several visual recognition tasks.

6.
Biosci Rep ; 39(11)2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31696217

RESUMO

Latarjet osteotomy is still one of the most reliable and commonly used surgeries in treating recurrent anterior shoulder dislocation. The coracoid process (CP) is the main structure of this surgery. However, the blood supply of CP is not fully understood, and the extent of destruction of blood supply of coracoid bone graft after Latarjet osteotomy procedure is still controversial. Five embalmed cadaveric upper limbs specimens were employed for macro observation of the blood supply of CP. The conjoint tendon (CT) and CP interface were dissected for histology. Sixteen fresh frozen shoulder specimens were used for perfusion and micro CT scanning. Eight specimens were used to present the whole vessel structure of CP. The other eight underwent Latarjet osteotomy procedure. The coracoid bone grafts in both groups were scanned to clarify the remnant blood supply. It was found that the CP was nourished by supra-scapular artery (SSA), thoracic-acromial artery and branch from second portion of the axillary artery (AA). After Latarjet osteotomy procedure, no artery from CT was detected to penetrate the CP at its attachment. Only in one specimen the blood vessel that originated from the CT penetrated the bone graft at the inferior side. Therefore, most of the blood supply was destroyed although there is a subtle possibility that the vessels derived from the CT nourished the inferior side of the CP. In a nutshell, CP is a structure with rich blood supply. The traditional Latarjet osteotomy procedure would inevitably cut off the blood supply of the coracoid bone graft.

8.
Artigo em Inglês | MEDLINE | ID: mdl-31742383

RESUMO

Inspired by the highly importance of hollow structures in nature such as blood vessels and bamboos in matter transportation, properties enhancement or even survival of living creatures, the creation of hollow materials remains considerable interest. However, constructing hollow unique living-like soft and wet polymeric hydrogels with desirable structures and functionalities is still a big challenge. Here, we reported a robust and effective strategy to fabricate complex three-dimensional hollow polymeric hydrogel with designed shape and function diversity on the basis of supramolecular interactions. Through placing a Ca2+ included gelatin core into the solution of alginate, hydrogel shell could be formed along the shape of the gelatin core via coordination between alginate chains and Ca2+ diffused from gelatin. Hollow hydrogel could finally be obtained by dissolving the gelatin core. Various complex 3D hollow structures could be achieved by designing/constructing assembled gelatin core as building block with adjustable supramolecular metal coordination position and strength. Moreover, hollow hydrogels with function diversity could be developed by introducing functional polymers or nanoparticles into the hydrogel wall. This work has made important progress in developing hollow polymeric hydrogel with desirable structures, shapes and various functional applications including soft actuators and chemical reaction containers.

9.
Opt Express ; 27(19): 26432-26445, 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31674525

RESUMO

Owing to the weak signals produced by all-fiber coherent lidar systems, when the instability of the local oscillator laser power is greater than the target echo signal, it is difficult to extract a target's intensity image. In this study, an intensity imaging method for weak signal all-fiber lidars is proposed. First, a phase compensation method is used to correct the position of the heterodyne signal in the time domain to reduce the impact of noise on the positioning heterodyne signal. In addition, an algorithm is proposed to extract the weak echo signal from the corrected heterodyne signal in the time domain to obtain the relative intensity of the echo signal of a single pixel point. Finally, we analyze and verify the proposed imaging method by using false alarm rates, range, intensity accuracy, and the speckle characteristics of the target. The method proposed in this study only requires that the phase of the heterodyne signal be corrected by the proposed numerical method without the need for other optical equipment, thus simplifying the entire system. It is very important to improve the detection sensitivity of coherent lidar remote imaging system.

10.
Cell ; 179(4): 864-879.e19, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31675497

RESUMO

Physical or mental stress leads to neuroplasticity in the brain and increases the risk of depression and anxiety. Stress exposure causes the dysfunction of peripheral T lymphocytes. However, the pathological role and underlying regulatory mechanism of peripheral T lymphocytes in mood disorders have not been well established. Here, we show that the lack of CD4+ T cells protects mice from stress-induced anxiety-like behavior. Physical stress-induced leukotriene B4 triggers severe mitochondrial fission in CD4+ T cells, which further leads to a variety of behavioral abnormalities including anxiety, depression, and social disorders. Metabolomic profiles and single-cell transcriptome reveal that CD4+ T cell-derived xanthine acts on oligodendrocytes in the left amygdala via adenosine receptor A1. Mitochondrial fission promotes the de novo synthesis of purine via interferon regulatory factor 1 accumulation in CD4+ T cells. Our study implicates a critical link between a purine metabolic disorder in CD4+ T cells and stress-driven anxiety-like behavior.

11.
Nitric Oxide ; 94: 125-134, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31759970

RESUMO

Microglia population is primarily determined by a finely-regulated proliferation process during early development of the central nervous system (CNS). Nitric oxide (NO) is known to inhibit proliferation in numerous cell types. However, how NO signaling regulates microglia proliferation remains elusive. Using wildtype (WT) and inducible nitric oxide synthase knockout (iNOS-/-) mice, this study investigated the role and underlying mechanisms of iNOS/NO signaling in microglia proliferation. Here we reported that iNOS-/- mice displayed significantly more BrdU-labeled proliferating microglia in the cortex than that in WT mice at postnatal day 10. Compared to microglia isolated from WT mouse cortex, significantly more iNOS-/- microglia displayed the specific cell-cycle markers Ki67 and phospho-histone H3 (pH3) in their nuclei. In addition, treating WT microglia with the NOS inhibitor LNAME drastically increased the percentage of cells expressing Ki67 and pH3, whereas treating iNOS-/- microglia with NOC18, a slow-release NO-donor, significantly decreased the percentage of microglia expressing the two cell-cycle markers. Moreover, inhibition of protein kinase-G (PKG) in WT microglia increased the proportion of microglia expressing Ki67 and pH3, whereas activation of PKG signaling using 8Br-cGMP in iNOS-/- microglia significantly decreased the fraction of microglia displaying Ki67 and pH3. Interestingly, in the presence of a PKG inhibitor, NOC18 increased the quantity of iNOS-/- microglia expressing Ki67 and pH3. Together, these results indicate that basal activity of iNOS/NO signaling impedes microglial cell-cycle progression and attenuates proliferation through activation of the cGMP-PKG pathway. However, NO increases microglia cell-cycle progression in the absence of cGMP-PKG signaling.

12.
Am J Sports Med ; : 363546519887959, 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31765231

RESUMO

BACKGROUND: Some studies have advocated the use of suture-button fixation during the Latarjet procedure to reduce complications associated with screw fixation. However, the sample size of these studies is relatively small, and their follow-up period is short. PURPOSE: To investigate the efficacy of the suture-button Latarjet procedure with at least 3 years of follow-up and remodeling of the coracoid graft. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A total of 152 patients who underwent the suture-button Latarjet procedure between February 2013 and February 2016 were selected, and 128 patients who met the inclusion criteria were enrolled in this study. Preoperative and postoperative clinical results were assessed. The position and healing condition of the coracoid graft and arthropathy of the glenoid and humeral head were also assessed using radiography and 3-dimensional computed tomography (CT). RESULTS: The mean follow-up time was 40.3 ± 5.8 months. There were 102 patients included in this study. The mean visual analog scale score for pain during motion, the American Shoulder and Elbow Surgeons score, the Rowe score, and the Walch-Duplay score were improved considerably. A total of 100 grafts achieved bone union. The overall absorption rate was 12.6% ± 4.3%. Graft absorption mostly occurred on the edge and outside the "best-fit" circle of the glenoid. A vertical position was achieved in 98 grafts (96% of all cases) immediately postoperatively, with the mean graft midline center at the 4 o'clock position. In the axial view, CT showed that 89 grafts were flush to the glenoid, whereas 2 and 11 grafts were fixed medially and laterally, respectively. In all cases, the bone graft and glenoid tended to extend toward each other to form concentric circles during the remodeling process. During follow-up observations, the height of the 11 grafts that were positioned laterally (ie, above the glenoid level) exhibited a wave-curved change. No arthropathy was observed in any patient. CONCLUSION: Patient outcomes were satisfactory after the modified arthroscopic suture-button Latarjet technique. Graft absorption mostly occurred on the edge and outside the "best-fit" circle of the glenoid. The graft exhibited the phenomenon of ectatic growing when it fused with the glenoid and finally remodeled to a new concentric circle with the humeral head analogous to the original glenoid. Grafts positioned laterally did not cause arthropathy of the joints within the period of the study.

13.
ACS Appl Mater Interfaces ; 11(47): 44609-44616, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31684720

RESUMO

In this study, we demonstrated the Au-catalyzed growth of free-standing defect-free zinc-blende structured InAs nanobelts on the GaAs {111}B substrate by molecular beam epitaxy. Through detailed morphological, chemical, and structural characterizations using advanced electron microscopy, it was found that the nanobelts grew along the ⟨001̅⟩ direction, induced by Au catalysts via vapor-solid-solid mechanism, with features of {001̅} catalyst/nanobelt interfaces and extensive {11̅0} surfaces. The formation of the belt-shaped morphology of our nanostructures resulted from a faster lateral growth rate along the ±[110] direction than that along the ±[11̅0] direction, driven by polarity. This study provides insights into understanding the growth of free-standing zinc-blende structured <001̅> InAs nanobelts.

14.
Small ; : e1903362, 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31736239

RESUMO

Recent years have witnessed rapid progresses made in the photoelectric performance of two-dimensional materials represented by graphene, black phosphorus, and transition metal dichalcogenides. Despite significant efforts, a photodetection technique capable for longer wavelength, higher working temperature as well as fast responsivity, is still facing huge challenges due to a lack of best among bandgap, dark current, and absorption ability. Exploring topological materials with nontrivial band transport leads to peculiar properties of quantized phenomena such as chiral anomaly, and magnetic-optical effect, which enables a novel feasibility for an advanced optoelectronic device working at longer wavelength. In this work, the direct generation of photocurrent at low energy terahertz (THz) band at room temperature is implemented in a planar metal-PtTe2 -metal structure. The results show that the THz photodetector based on PtTe2 with bow-tie-type planar contacts possesses a high photoresponsivity (1.6 A W-1 without bias voltage) with a response time less than 20 µs, while the PtTe2 -graphene heterostructure-based detector can reach responsivity above 1.4 kV W-1 and a response time shorter than 9 µs. Remarkably, it is already exploitable for large area imaging applications. These results suggest that topological semimetals such as PtTe2 can be ideal materials for implementation in a high-performing photodetection system at THz band.

16.
Nature ; 575(7783): 473-479, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31748722

RESUMO

Traditional technologies for virtual reality (VR) and augmented reality (AR) create human experiences through visual and auditory stimuli that replicate sensations associated with the physical world. The most widespread VR and AR systems use head-mounted displays, accelerometers and loudspeakers as the basis for three-dimensional, computer-generated environments that can exist in isolation or as overlays on actual scenery. In comparison to the eyes and the ears, the skin is a relatively underexplored sensory interface for VR and AR technology that could, nevertheless, greatly enhance experiences at a qualitative level, with direct relevance in areas such as communications, entertainment and medicine1,2. Here we present a wireless, battery-free platform of electronic systems and haptic (that is, touch-based) interfaces capable of softly laminating onto the curved surfaces of the skin to communicate information via spatio-temporally programmable patterns of localized mechanical vibrations. We describe the materials, device structures, power delivery strategies and communication schemes that serve as the foundations for such platforms. The resulting technology creates many opportunities for use where the skin provides an electronically programmable communication and sensory input channel to the body, as demonstrated through applications in social media and personal engagement, prosthetic control and feedback, and gaming and entertainment.

17.
Nat Commun ; 10(1): 5230, 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31745089

RESUMO

The Hengduan Mountains (HDM) biodiversity hotspot exhibits exceptional alpine plant diversity. Here, we investigate factors driving intraspecific divergence within a HDM alpine species Salix brachista (Cushion willow), a common component of subnival assemblages. We produce a high-quality genome assembly for this species and characterize its genetic diversity, population structure and pattern of evolution by resequencing individuals collected across its distribution. We detect population divergence that has been shaped by a landscape of isolated sky island-like habitats displaying strong environmental heterogeneity across elevational gradients, combined with population size fluctuations that have occurred since approximately the late Miocene. These factors are likely important drivers of intraspecific divergence within Cushion willow and possibly other alpine plants with a similar distribution. Since intraspecific divergence is often the first step toward speciation, the same factors can be important contributors to the high alpine species diversity in the HDM.

18.
Molecules ; 24(23)2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31757115

RESUMO

The pentafluorosulfane (SF5) group, as a more electronegative bioisostere than the trifluoromethyl (CF3) group, has been gaining greater attention and increasingly reported usage in medicinal chemistry. Ostarine is the selective androgen receptor modulators (SARMs) containing a CF3 group in clinical trial III. In this study, 21 ostarine derivatives for replacing the CF3 group with SF5 substituents were synthesized. Some SF5-derivatives showed androgen receptor (AR) agonistic activities in vitro. The results pointed to the potential of using this scaffold to develop new AR agonists.

19.
Int Immunopharmacol ; : 105954, 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31757676

RESUMO

Osteoarthritis (OA) is a chronic inflammatory disease that is the basis of cartilage extracellular matrix degeneration and joint inflammation. Scutellarin is an herbal flavonoid glucuronide, isolated from the Chinese traditional herb Erigeron breviscapus, has been reported to have anti-inflammatory effect. Here, we showed that Scutellarin could inhibit inflammation and protects cartilage from degeneration in vitro and in vivo. Scutellarin downregulate the mRNA and protein expression of MMP1, MMP13, and ADAMTS-5, Wnt3a, Frizzled7 and promote the expression of Collagen II and Aggrecan. Moreover, scutellarin inhibit the migration of ß-catenin and phosphorylation of p38 into the nucleus, which may relate to the mediation of the Wnt/ß-catenin and MAPK signaling pathway. Furthermore, scutellarin significantly inhibit the cartilage degradation of DMM-induced OA mice by safranin-O and fast green staining. In conclusion, our study indicates that scutellarin may be a potential drug for the treatment of OA.

20.
Artigo em Inglês | MEDLINE | ID: mdl-31724280

RESUMO

Herein, a sensitive amine-responsive disassembly of self-assembled Au(I)-Cu(I) double salts was observed and its utilization for the synergistic catalysis was further enlightened. Investigation of the disassembly of [Au(NHC)2][CuI2] revealed the contribution of Cu-assisted ligand exchange of N-heterocyclic carbene (NHC) by amine in [Au(NHC)2]+ and the capacity of [CuI2]- on the oxidative step. By integrating the implicative information coded in the responsive behaviour and inherent catalytic functions of d10 metal complexes, we have developed a novel catalyst for the oxidative carbonylation of amines. The advantages of this protocol were clearly reflected on mild reaction condtion and the significantly expanded scope (51 examples); both primary and steric secondary amines can be employed as substrates. The cooperative reactivity from Au and Cu centers, as an indispensable prerequisite for the excellent catalytic performance, was validated in the synthesis of (un)symmetric ureas and carbamates.

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