The administration of bone mesenchymal stem cells (BMSCs) could reverse experimental colitis, and the predominant mechanism in tissue repair seems to be related to their paracrine activity. BMSCs ...derived extracellular vesicles (BMSC-EVs), including mcirovesicles and exosomes, containing diverse proteins, mRNAs and micro-RNAs, mediating various biological functions, might be a main paracrine mechanism for stem cell to injured cell communication. We aimed to investigate the potential alleviating effects of BMSC-EVs in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis model. Intravenous injection of BMSC-EVs attenuated the severity of colitis as evidenced by decrease of disease activity index (DAI) and histological colonic damage. In inflammation response, the BMSC-EVs treatment significantly reduced both the mRNA and protein levels of nuclear factor kappaBp65 (NF-κBp65), tumor necrosis factor-alpha (TNF-α), induciblenitric oxidesynthase (iNOS) and cyclooxygenase-2 (COX-2) in injured colon. Additionally, the BMSC-EVs injection resulted in a markedly decrease in interleukin-1β (IL-1β) and an increase in interleukin-10 (IL-10) expression. Therapeutic effect of BMSC-EVs associated with suppression of oxidative perturbations was manifested by a decrease in the activity of myeloperoxidase (MPO) and Malondialdehyde (MDA), as well as an increase in superoxide dismutase (SOD) and glutathione (GSH). BMSC-EVs also suppressed the apoptosis via reducing the cleavage of caspase-3, caspase-8 and caspase-9 in colitis rats. Data obtained indicated that the beneficial effects of BMSC-EVs were due to the down regulation of pro-inflammatory cytokines levels, inhibition of NF-κBp65 signal transduction pathways, modulation of anti-oxidant/ oxidant balance, and moderation of the occurrence of apoptosis.
•Geochemical baselines of heavy metals (HMs) were established in greenhouse soils.•The established baselines facilitated a more accurate HM evaluation.•Cd was considered to be the main contribution ...of soil contamination in this study.•Accumulation of Cd, Pb and Zn in surface soils ascribed to anthropogenic sources.
Currently, heavy metal (HM) contamination in greenhouse soils is a significant concern due to the rapid expansion of greenhouse agriculture. However, it is difficult to accurately assess HM pollution in greenhouse soils in China due to the lack of local geochemical baseline concentrations (GBCs) or corresponding background values. In the present study, the GBCs of HMs in Dongtai, a representative greenhouse area of China, were established from subsoils using cumulative frequency distribution (CFD) curves. The pollution levels of HMs and potential ecological risks were investigated using different quantitative indices, such as geo-accumulation index (Igeo), pollution index (PI), pollution load index (PLI) and ecological risk index (RI), based on these regional GBCs. The total concentrations of six metals (Cd, Cr, Cu, Ni, Pb and Zn) in surface soils were determined and shown to be lower than the concentrations reported in other greenhouse regions of China. The GBCs of Cd, Cr, Cu, Ni, Pb and Zn were 0.059–0.092, 39.20–54.50, 12.52–15.57, 20.63–23.26, 13.43–16.62 and 43.02–52.65mgkg−1, respectively. Based on this baseline criterion, Cd, Pb and Zn accumulated in the surface soils because they were present at concentrations higher than their baseline values. The soils were moderately polluted by Cd according to the Igeo values, and the PI results indicated that moderate Cd contamination was present in this area. The large variation of Igeo value of Cd revealed that Cd in this area was likely influenced by agricultural activities. The PLI showed that most of the study area was moderately polluted. However, an analysis of the RI showed that the investigated HMs had low ecological risks. Correlation analysis and principle component analysis suggested that the Cd, Pb and Zn in the greenhouse soils mainly originated from anthropogenic sources (agricultural activities, atmospheric deposition etc.), while Cr, Cu, and Ni originated from natural sources. The findings of this study illustrated the necessity of GBC establishment at the local scale to facilitate more accurate HM evaluation of greenhouse soils. It is advisable to pay more attention to Cd, which could cause environmental problems in the greenhouse system.
Research Summary
We examine how organizations govern interfirm transactions that involve innovative tasks. Designing contracts that foster innovation is challenging and becomes more complex when ...exchange hazards are present. We draw on regulatory focus theory to examine the effects of promotion and prevention effects in contract framing contracts to address how firms should design their contracts to balance the need for promoting innovation and protecting against opportunistic behavior. Using a sample of contracts from the information technology services industry, we find that in the presence of exchange hazards, task innovation involves hybrid payment systems, less use of detailed description of requirements, and more use of extensive contingency planning.
Managerial Summary
Managers must understand how contract design can aid in the success of interfirm innovation endeavors as radical innovation is frequently developed in an interfirm context. Our findings suggest that contract negotiators should pay special attention to several contractual elements when designing contracts for tasks that require more radical innovation. In particular, the payment structure, specifications of outcomes and processes, and contingency planning clauses influence the innovative output of suppliers. Employees who understand the task should participate in contract negotiation and design, allowing them to outsource more innovative tasks and manage them more effectively.
The topographic amplification effect has significant impacts on structural safety since it causes inconsistencies in seismic response. Previous studies on topographical influence focus on a certain ...point and cross-sections, which is insufficient to comprehensively understand the topographic amplification effect. Besides, few studies analyze the relationship between seismic response and ground motion frequency. Hence, this study aims to investigate the effects of topographic irregularity of the whole site, and explore the relationship between seismic response characteristics and signal frequency. An analysis procedure for modeling and meshing an actual 3D site is proposed by combining SolidWorks, SketchUp and Abaqus. Finite element method (FEM) is applied to simulate the seismic response. Results show that the site amplification and de-amplification are associated with topographic features. Specifically, the seismic responses of ravine and ridge areas could differ by a factor of two. However, acceleration response in ravine areas shows unusual amplification under input signal frequencies over 4 Hz. Besides, the frequency of input ground motion certainly affects the seismic site amplification. Specifically, in this study, the seismic response peaks when the input frequency is in the range of 0.4–0.8 Hz, which corresponds to the resonance frequency of the numerical model. In terms of frequency, site amplification showed a correlation between actual recordings and artificial signal inputs, but lower intensities are observed when actual records are input. Therefore, the engineering risk will be underestimated when the topographic irregularity and frequency characteristic of input ground motion are inappropriately considered. The findings of this study provide a new approach to investigate the actual 3D site amplification effects and shed new insight on regional seismic risk analysis.
•A method for generating numerical models of irregular 3D terrain is proposed.•The correlation between the seismic response and topographic characteristics of the valley at the actual site is investigated.•Seismic site amplification is closely related to input signal frequency.
The ambient electrocatalytic N2 reduction reaction (NRR) enabled by TiO2 has attracted extensive recent attention. Previous studies suggest the formation of Ti3+ in TiO2 can significantly improve the ...NRR activity, but it still remains unclear what kinds of Ti3+ are effective. Herein, it is demonstrated that mixed‐valent Cu acts as an effective dopant to modulate the oxygen vacancy (VO) concentration and Ti3+ formation, which markedly improves the electrocatalytic NRR performance. In 0.5 m LiClO4, this electrocatalyst attains a high Faradic efficiency of 21.99% and a large NH3 yield of 21.31 µg h−1 mgcat.−1 at –0.55 V vs reversible hydrogen electrode, which even surpasses most reported Ti‐based NRR electrocatalysts. Using density function theory calculations, it is evidenced that mixed‐valent Cu ions modulate the TiO2 (101) surface with multiple oxygen vacancies, which is beneficial for generating different Ti3+ 3d1 defect states localized below the Fermi energy. N2 activation and adsorption are effectively strengthened when Ti3+ 3d1 defect states present the splitting of eg and t2g orbitals, which can be modulated by its coordination structure. The synergistic roles of the three ion pairs formed by the VO defect, including Cu1+–Ti4+, Ti3+–Ti4+ and Ti3+–Ti3+, are together responsible for the enhanced NRR performance.
Cu‐doped TiO2 nanoparticles are highly active toward ambient N2‐to‐NH3 conversion with excellent selectivity. In 0.5 m LiClO4, this catalyst attains a high Faradaic efficiency of 21.99% and a large NH3 yield of 21.31 µg h‒1 mgcat.‒1 at ‒0.55 V versus reversible hydrogen electrode. Density function theory calculations are further discussed for the N2 reduction reaction catalytic mechanism on the Cu‐doped TiO2 (101) surface.
Background and Aim
Epithelial–mesenchymal transition (EMT), characterized by the decrease of E‐cadherin (E‐Cad) and increase in vimentin and alpha‐smooth muscle actin (α‐SMA), was demonstrated to ...participate in inflammatory bowel disease‐related fibrosis. miR‐200b plays an anti‐fibrosis role in inhibiting EMT by targeting ZEB1 and ZEB2. But the stability of exogenous miR‐200b in blood limits its application. Microvesicles (MVs), which can transfer miRNAs among cells and prevent them from degradation, may provide an excellent transport system for the delivery of miR‐200b in the treatment of fibrosis.
Methods
Bone marrow mesenchymal stem cells (BMSCs) were transfected with lentivirus to overexpress miR‐200b. The MVs packaged with miRNA‐200b were harvested for the anti‐fibrotic treatment using in vitro (transforming growth factor beta 1‐mediated EMT in intestinal epithelial cells: IEC‐6) and in vivo (TNBS‐induced intestinal fibrosis in rats) models. The pathological morphology was observed, and the fibrosis related proteins, such as E‐Cad, vimentin, α‐SMA, ZEB1, and ZEB2, were detected.
Results
MiR‐200b‐MVs would significantly reverse the morphology in TGF‐β1‐treated IEC‐6 cells and improve the TNBS‐induced colon fibrosis histologically. The treatment of miR‐200b‐MVs increased miR‐200b levels both in the IEC‐6 cells and colon, resulting in a significant prevention EMT and alleviation of fibrosis. The expression of E‐Cad was increased, and the expressions of vimentin and α‐SMA were decreased. ZBE1 and ZEB2, the targets of miR‐200b, were also decreased.
Conclusions
miR‐200b could be transferred from genetically modified BMSCs to the target cells or tissue by MVs. The mechanisms of miR‐200b‐MVs in inhibiting colonic fibrosis were related to suppressing the development of EMT by targeting ZEB1and ZEB2.
Diabetic microvascular complications, including diabetic kidney disease (DKD), retinopathy (DR), and neuropathy (DN), were major causes of morbidity and mortality in diabetic patients worldwide. It ...has been suggested that urinary albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) were not the only indicators of renal function impairment in DKD and that they were also associated with diabetic peripheral neuropathy (DPN) which might affect nerve conduction velocity (NCV). As 30–40% of DPN patients had no subjective symptoms, while current perception threshold (CPT) could detect sensory nerve damage at an early stage. As a result, we aimed to investigate correlation between UACR, eGFR and CPT in DKD patients.
A total of 273 DKD patients from the First Affiliated Hospital of Kunming Medical University from January 2018 to June 2020 were enrolled to complete the CPT test. CPT values of the bilateral median nerve and superficial and deep peroneal nerves at 2000 Hz, 250 Hz, and 5 Hz were collected.
In normoesthesia and hypaesthesia patients with DKD, MDRD-eGFR correlated negatively with TC (r = -0.135, P = 0.037), left superficial peroneal and deep peroneal nerve 2000 Hz CPT (r = -0.205, P = 0.001) and right superficial peroneal and deep peroneal nerve 2000 Hz CPT (r = -0.154, P = 0.017). Besides, left and right superficial peroneal and deep peroneal nerve 2000 Hz CPT correlated with CKD-EPI-eGFR and UACR. Multivariate logistic regression analysis found left superficial peroneal and deep peroneal nerve 2000 Hz CPT was independently associated with both MDRD-eGFR and CKD-EPI-eGFR.
Decreased MDRD-eGFR and CKD-EPI-eGFR were expected to be a predictor of peripheral nerve injury in normoesthesia and hypaesthesia patients with DKD.
•Temperature compensation is discussed by considering interfacial action between the monitored structure and bonded FBG sensors.•Modified temperature-compensation function is proposed to enhance ...measurement accuracy of FBG sensors.•Effectiveness of the proposed function is validated by experiments.•Improved temperature-compensation measures for FBG sensors applied to structures under different loading conditions are suggested.•Hysteretic response time of FBG sensors is discussed and proper packaging design is experimentally proved to be feasible for decreasing the response time of FBG under thermal loading.
Fiber Bragg grating (FBG) based sensors have been extensively used to monitor the deformation of structures (i.e., aircrafts, ocean platforms, bridges, tunnels, pavements and high-speed railways), for the advantages of absolute measurement, anti-electromagnetic interference, high precision, multiplexing and integration of sensing network over other sensors. However, due to the temperature-sensitive characteristics of FBG, temperature compensation should be considered to remove the thermal effect, so as to accurately reflect the strain information of the monitored structure. Traditional temperature-compensation method ignores the influence of the interfacial interaction between the structure and the bonded FBG on the measured data, which may lead to the compensated value smaller than the actual value. For this reason, modified temperature-compensation function with the influence of interfacial action considered is proposed to enhance the measurement accuracy of FBG based sensors. Laboratory tests on two kinds of samples under temperature loading have been conducted to validate the effectiveness of the proposed function. Improved temperature-compensation measures for FBG based sensors applied to structures under different loading conditions (i.e., high and low temperature, static and dynamic mechanical load) are discussed, with the temperature hysteresis of FBG sensing elements considered. The study in this paper presents a scientific instruction for the better interpretation of testing data measured by FBG sensors and the accurate use of FBG sensors for the temperature and strain detection of structures in engineering
As the most aggressive tumor, the outcome of pancreatic cancer (PACA) has not improved observably over the last decade. Anatomy-based TNM staging does not exactly identify treatment-sensitive ...patients, and an ideal biomarker is urgently needed for precision medicine. Based on expression files of 1280 patients from 10 multicenter cohorts, we screened 32 consensus prognostic genes. Ten machine-learning algorithms were transformed into 76 combinations, of which we selected the optimal algorithm to construct an artificial intelligence-derived prognostic signature (AIDPS) according to the average C-index in the nine testing cohorts. The results of the training cohort, nine testing cohorts, Meta-Cohort, and three external validation cohorts (290 patients) consistently indicated that AIDPS could accurately predict the prognosis of PACA. After incorporating several vital clinicopathological features and 86 published signatures, AIDPS exhibited robust and dramatically superior predictive capability. Moreover, in other prevalent digestive system tumors, the nine-gene AIDPS could still accurately stratify the prognosis. Of note, our AIDPS had important clinical implications for PACA, and patients with low AIDPS owned a dismal prognosis, higher genomic alterations, and denser immune cell infiltrates as well as were more sensitive to immunotherapy. Meanwhile, the high AIDPS group possessed observably prolonged survival, and panobinostat may be a potential agent for patients with high AIDPS. Overall, our study provides an attractive tool to further guide the clinical management and individualized treatment of PACA.
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