Diabetic nephropathy (DN) remains one of the severe complications associated with diabetes mellitus. It is worthwhile to uncover the underlying mechanisms of clinical benefits of human urine‐derived ...stem cells (hUSCs) in the treatment of DN. At present, the clinical benefits associated with hUSCs in the treatment of DN remains unclear. Hence, our study aims to investigate protective effect of hUSC exosome along with microRNA‐16‐5p (miR‐16‐5p) on podocytes in DN via vascular endothelial growth factor A (VEGFA). Initially, miR‐16‐5p was predicated to target VEGFA based on data retrieved from several bioinformatics databases. Notably, dual‐luciferase report gene assay provided further verification confirming the prediction. Moreover, our results demonstrated that high glucose (HG) stimulation could inhibit miR‐16‐5p and promote VEGFA in human podocytes (HPDCs). miR‐16‐5p in hUSCs was transferred through the exosome pathway to HG‐treated HPDCs. The viability and apoptosis rate of podocytes after HG treatment together with expression of the related factors were subsequently determined. The results indicated that miR‐16‐5p secreted by hUSCs could improve podocyte injury induced by HG. In addition, VEGA silencing could also ameliorate HG‐induced podocyte injury. Finally, hUSC exosomes containing overexpressed miR‐16‐5p were injected into diabetic rats via tail vein, followed by qualification of miR‐16‐5p and observation on the changes of podocytes, which revealed that overexpressed miR‐16‐5p in hUSCs conferred protective effects on HPDCs in diabetic rats. Taken together, the present study revealed that overexpressed miR‐16‐5p in hUSC exosomes could protect HPDCs induced by HG and suppress VEGFA expression and podocytic apoptosis, providing fresh insights for novel treatment of DN.
Review of hair follicle dermal cells Yang, Chao-Chun; Cotsarelis, George
Journal of dermatological science,
01/2010, Volume:
57, Issue:
1
Journal Article
Peer reviewed
Open access
Abstract Hair follicle stem cells in the epithelial bulge are responsible for the continual regeneration of the hair follicle during cycling. The bulge cells reside in a niche composed of dermal ...cells. The dermal compartment of the hair follicle consists of the dermal papilla and dermal sheath. Interactions between hair follicle epithelial and dermal cells are necessary for hair follicle morphogenesis during development and in hair reconstitution assays. Dermal papilla and dermal sheath cells express specific markers and possess distinctive morphology and behavior in culture. These cells can induce hair follicle differentiation in epithelial cells and are required in hair reconstitution assays either in the form of intact tissue, dissociated freshly prepared cells or cultured cells. This review will focus on hair follicle dermal cells since most therapeutic efforts to date have concentrated on this aspect of the hair follicle, with the idea that enriching hair-inductive dermal cell populations and expanding their number by culture while maintaining their properties, will establish an efficient hair reconstitution assay that could eventually have therapeutic implications.
Internal short-circuit is the most dangerous abusive condition for Li-ion batteries and has been the root cause for several catastrophic accidents involving Li-ion batteries in recent years. ...Large-format Li-ion batteries are particularly vulnerable to internal short-circuits because of high energy content. Nail penetration test is commonly used to study the internal short-circuits, but the test results usually have poor reproducibility and offer limited insight. In this work, a 3 D multiscale electrochemical-thermal coupled model is used to investigate the nail penetration process in a large-format Li-ion cell. A parametric study is carried out and the results reveal strong coupling of the cell thermal response and electrochemical behaviour, which is influenced substantially by key parameters including shorting resistance, nail diameter, nail thermal conductivity, and cell capacity. The present study provides some insight that will help design more reliable experimental internal short-circuit testing protocols and improve the abuse tolerance of Li-ion cells.
A recent study suggests that the streaming instability, one of the leading mechanisms for driving the formation of planetesimals,
may not be as efficient as previously thought. Under some disc ...conditions, the growth time-scale of the instability can be longer
than the disc lifetime when multiple dust species are considered. To further explore this finding, we use both linear analysis and
direct numerical simulations with gas fluid and dust particles tomutually validate and study the unstablemodes of the instability in
more detail.We extend the previously studied parameter space by one order of magnitude in both the range of the dust-size distribution
Ts, min, Ts, max and the total solid-to-gas mass ratio ε and introduce a third dimension with the slope q of the size distribution.
We find that the fast-growth regime and the slow-growth regime are distinctly separated in the ε–Ts, max space, while this boundary
is not appreciably sensitive to q or Ts, min.With a wide range of dust sizes present in the disc (e.g. Ts, min 10−3), the growth rate
in the slow-growth regime decreases as more dust species are considered.With a narrow range of dust sizes (e.g. Ts, max/Ts, min =
5), on the other hand, the growth rate in most of the ε–Ts, max space is converged with increasing dust species, but the fast and the
slow growth regimes remain clearly separated. Moreover, it is not necessary that the largest dust species dominate the growth of
the unstable modes, and the smaller dust species can affect the growth rate in a complicated way. In any case, we find that the
fast-growth regime is bounded by ε 1 or Ts, max 1, which may represent the favourable conditions for planetesimal formation.
The High-tech Industrial Development Districts (HIDDs) are technological engines for the regional economy in China. The Chinese government implemented the Torch Initiative to accelerate industrial ...agglomeration and innovation development by administratively upgrading the local HIDDs into a national list since 1989. The policy intervention emphasizes the labor and capital inputs on science and technology. The study adopts the Stochastic Frontier Analysis (SFA) to understand the economic efficiency of the enlisted national HIDDs in the Yangtze River Delta. The results suggest that the average efficiency trends of the all-in-total sales, product sales and commodity sales are decreasing while that of technology sales is increasing from 2007 to 2019. In the total sales efficiency evaluation, most early-enrolled HIDDs are in the high-efficiency group whereas the newcomers are in the low-efficiency group. The Nantong HIDD has the highest efficiency, followed by Wuxi, Taizhou, Suzhou, Nanjing, Shanghai ZJ, Xiaoshan, Ningbo, Suzhou IP and Jiangyin HIDDs. Huainan, Huaian, Tongling, Shanghai ZZ, Lianyungang and Suqian HIDDs rank very low in the total sales evaluation. Besides, Hangzhou, Nantong and Ningbo HIDDs rank first in the technology, product and commodity sales efficiency evaluation correspondingly. In addition, the increase of S&T labor inputs would decrease the efficiency of the product, commodity and total sales while the increase of the S&T capital inputs is as expected a facilitator to the efficiency of product, commodity and total sales. This study contributes to the discussion on the role of political intervention in technological innovation by breaking down the economic efficiency into three major parts, the efficiency of technology, product and commodity sales. The findings could help policymakers strike a balance between the human and capital inputs in regional innovation capability.
Where are the new herbicides? Qu, Ren‐Yu; He, Bo; Yang, Jing‐Fang ...
Pest management science,
June 2021, 2021-Jun, 2021-06-00, 20210601, Volume:
77, Issue:
6
Journal Article
Efficient exciton diffusion and charge transport play a vital role in advancing the power conversion efficiency (PCE) of organic solar cells (OSCs). Here, a facile strategy is presented to ...simultaneously enhance exciton/charge transport of the widely studied PM6:Y6‐based OSCs by employing highly emissive trans‐bis(dimesitylboron)stilbene (BBS) as a solid additive. BBS transforms the emissive sites from a more H‐type aggregate into a more J‐type aggregate, which benefits the resonance energy transfer for PM6 exciton diffusion and energy transfer from PM6 to Y6. Transient gated photoluminescence spectroscopy measurements indicate that addition of BBS improves the exciton diffusion coefficient of PM6 and the dissociation of PM6 excitons in the PM6:Y6:BBS film. Transient absorption spectroscopy measurements confirm faster charge generation in PM6:Y6:BBS. Moreover, BBS helps improve Y6 crystallization, and current‐sensing atomic force microscopy characterization reveals an improved charge‐carrier diffusion length in PM6:Y6:BBS. Owing to the enhanced exciton diffusion, exciton dissociation, charge generation, and charge transport, as well as reduced charge recombination and energy loss, a higher PCE of 17.6% with simultaneously improved open‐circuit voltage, short‐circuit current density, and fill factor is achieved for the PM6:Y6:BBS devices compared to the devices without BBS (16.2%).
The exciton diffusion and charge transport of PM6:Y6‐based organic solar cells are simultaneously enhanced by trans‐bis(dimesitylboron)stilbene (BBS), and the PM6:Y6:BBS devices achieve a higher efficiency of 17.6% relative to that without BBS (16.2%).
Src homology 2 domain-containing phosphatase 2 (SHP2) is an attractive therapeutic target for human cancers and other human diseases. Herein, we report our discovery of potent small-molecule SHP2 ...degraders whose design is based upon the proteolysis-targeting chimera (PROTAC) concept. This work has led to the discovery of potent and effective SHP2 degraders, exemplified by SHP2-D26. SHP2-D26 achieves DC50 values of 6.0 and 2.6 nM in esophageal cancer KYSE520 and acute myeloid leukemia MV4;11 cells, respectively, and is capable of reducing SHP2 protein levels by >95% in cancer cells. SHP2-D26 is >30-times more potent in inhibition of phosphorylation of extracellular signal-regulated kinase (ERK) and of cell growth than SHP099, a potent SHP2 inhibitor, in KYSE520 and MV4;11 cancer cell lines. This study demonstrates that induced SHP2 degradation is a very effective approach to inhibit the function of SHP2. Further optimization of these SHP2 degraders may lead to the development of a new class of therapies for cancers and other human diseases.
Intervertebral disc degeneration (IVDD) is one of the leading causes of low back pain and one of the most common health problems in the world. The nucleotide-binding oligomerization domain-like ...receptor family pyrin domain-containing-3 (NLRP3) inflammasome, as a pattern recognition receptor, has been shown to be associated with the pathological processes of many diseases in recent years. With the exploration of the mechanism of IVDD, recent studies have shown that activation of the NLRP3 inflammasome is associated with intervertebral disc (IVD) inflammation, pyroptosis, extracellular matrix degradation and apoptosis of IVD cells. In this review, we summarize the structural characteristics of NLRP3 inflammasome and the activation signalling mechanisms. We also describe the role of the NLRP3 inflammasome in the pathological process of IVDD and the application of the targeting the NLRP3 inflammasome in IVDD treatment.
An outbreak of betacoronavirus severe acute respiratory syndrome (SARS)-CoV-2 began in Wuhan, China in December 2019. COVID-19, the disease associated with SARS-CoV-2 infection, rapidly spread to ...produce a global pandemic. We report development of a rapid (<40 min), easy-to-implement and accurate CRISPR-Cas12-based lateral flow assay for detection of SARS-CoV-2 from respiratory swab RNA extracts. We validated our method using contrived reference samples and clinical samples from patients in the United States, including 36 patients with COVID-19 infection and 42 patients with other viral respiratory infections. Our CRISPR-based DETECTR assay provides a visual and faster alternative to the US Centers for Disease Control and Prevention SARS-CoV-2 real-time RT-PCR assay, with 95% positive predictive agreement and 100% negative predictive agreement.
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