Exosome therapy is a promising therapeutic approach for intervertebral disc degeneration (IVDD) and achieves its therapeutic effects by regulating metabolic disorders, the microenvironment and cell ...homeostasis with the sustained release of microRNAs, proteins, and transcription factors. However, the rapid clearance and disruption of exosomes are the two major challenges for the application of exosome therapy in IVDD. Herein, a thermosensitive acellular extracellular matrix (ECM) hydrogel coupled with adipose-derived mesenchymal stem cell (ADSC) exosomes (dECM@exo) that inherits the superior properties of nucleus pulposus tissue and ADSCs was fabricated to ameliorate IVDD. This thermosensitive dECM@exo hydrogel system can provide not only in situ gelation to replenish ECM leakage in nucleus pulposus cells (NPCs) but also an environment for the growth of NPCs. In addition, sustained release of ADSC-derived exosomes from this system regulates matrix synthesis and degradation by regulating matrix metalloproteinases (MMPs) and inhibits pyroptosis by mitigating the inflammatory response in vitro. Animal results demonstrated that the dECM@exo hydrogel system maintained early IVD microenvironment homeostasis and ameliorated IVDD. This functional system can serve as a powerful platform for IVD drug delivery and biotherapy and an alternative therapy for IVDD.
New constraints are presented on the spin-dependent weakly-interacting-massive-particle- (WIMP-)nucleon interaction from the PandaX-II experiment, using a data set corresponding to a total exposure ...of 3.3×10^{4} kg day. Assuming a standard axial-vector spin-dependent WIMP interaction with ^{129}Xe and ^{131}Xe nuclei, the most stringent upper limits on WIMP-neutron cross sections for WIMPs with masses above 10 GeV/c^{2} are set in all dark matter direct detection experiments. The minimum upper limit of 4.1×10^{-41} cm^{2} at 90% confidence level is obtained for a WIMP mass of 40 GeV/c^{2}. This represents more than a factor of 2 improvement on the best available limits at this and higher masses. These improved cross-section limits provide more stringent constraints on the effective WIMP-proton and WIMP-neutron couplings.
We report new searches for solar axions and galactic axionlike dark matter particles, using the first low-background data from the PandaX-II experiment at China Jinping Underground Laboratory, ...corresponding to a total exposure of about 2.7×10^{4} kg day. No solar axion or galactic axionlike dark matter particle candidate has been identified. The upper limit on the axion-electron coupling (g_{Ae}) from the solar flux is found to be about 4.35×10^{-12} in the mass range from 10^{-5} to 1 keV/c^{2} with 90% confidence level, similar to the recent LUX result. We also report a new best limit from the ^{57}Fe deexcitation. On the other hand, the upper limit from the galactic axions is on the order of 10^{-13} in the mass range from 1 to 10 keV/c^{2} with 90% confidence level, slightly improved compared with the LUX.
Cerebrospinal fluid (CSF) in the paravascular spaces of the surface arteries (sPVS) is a vital pathway in brain waste clearance. Arterial pulsations may be the driving force of the paravascular flow, ...but its pulsatile pattern remains poorly characterized, and no clinically practical method for measuring its dynamics in the human brain is available. In this work, we introduce an imaging and quantification framework for in-vivo non-invasive assessment of pulsatile fluid dynamics in the sPVS. It used dynamic Diffusion-Weighted Imaging (dDWI) at a lower b-values of 150s/mm
2
and retrospective gating to detect the slow flow of CSF while suppressing the fast flow of adjacent arterial blood. The waveform of CSF flow over a cardiac cycle was revealed by synchronizing the measurements with the heartbeat. A data-driven approach was developed to identify sPVS and allow automatic quantification of the whole-brain fluid waveforms. We applied dDWI to twenty-five participants aged 18–82 y/o. Results demonstrated that the fluid waveforms across the brain showed an explicit cardiac-cycle dependency, in good agreement with the vascular pumping hypothesis. Furthermore, the shape of the CSF waveforms closely resembled the pressure waveforms of the artery wall, suggesting that CSF dynamics is tightly related to artery wall mechanics. Finally, the CSF waveforms in aging participants revealed a strong age effect, with a significantly wider systolic peak observed in the older relative to younger participants. The peak widening may be associated with compromised vascular compliance and vessel wall stiffening in the older brain. Overall, the results demonstrate the feasibility, reproducibility, and sensitivity of dDWI for detecting sPVS fluid dynamics of the human brain. Our preliminary data suggest age-related alterations of the paravascular pumping. With an acquisition time of under six minutes, dDWI can be readily applied to study fluid dynamics in normal physiological conditions and cerebrovascular/neurodegenerative diseases.
•The implementation of the GLC project will have a two-sided effect on soil erosion.•Reservoir modification is the most important factor affecting the gully erosion.•Erosion can be reduced by slope, ...leveling and hydraulic engineering optimization modifications.
The effect of land use on erosion over space and time is relevant. In this study, two types of land-use management practices, the gully land consolidation (GLC) project and the land consolidation (LC) project, were applied on the Loess Plateau. Based on the soil erosion that occurred from 2010 to 2019, the spatial distribution, spatiotemporal evolution and susceptibility map of soil erosion were analyzed by geospatial analysis, statistical methods and frequency ratio (FR) models. The results showed that the implementation of the GLC project can have two effects on soil erosion. Firstly, a large amount of slope erosion was caused by slope excavation in the GLC watershed; secondly, the amount and scale of gully erosion were effectively controlled by hydraulic engineering. In addition, the unreasonable hydraulic engineering of the LC project can cause large areas of soil erosion. The influencing factors of gully erosion can be ranked as follows: reservoir > elevation > dam land > flow length > geology > LS. Three aspects of engineering optimization measures for the GLC project were proposed: 1. Slope excavation should be reduced, and diverse slope protections should be implemented in this project, especially for the bottom of the slope, which should adopt different measures than the top of the slope. 2. For trenches within 1.2 km of the gully head, more attention should focus on soil and water conservation measures than on land leveling. 3. Hydraulic engineering and irrigation and drainage engineering should effectively cooperate with leveling projects and adjust the applied measures to the local conditions and the natural shape of the original rivers. As a new land-use management approach, our results highlight that little is known about the effect of the GLC project on soil erosion, and our results can provide specific guidance for the next step of project implementation.
Despite being considered the standard surgical procedure for symptomatic cervical disc disease, anterior cervical decompression and fusion invariably accelerates adjacent segment degeneration. ...Cervical total disc replacement is a motion-preserving procedure developed as a substitute to fusion. Whether cervical total disc replacement is superior to fusion remains unclear.
We comprehensively searched PubMed, EMBASE, Medline, and the Cochrane Library in accordance with the inclusion criteria to identify possible studies. The retrieved results were last updated on December 12, 2014. We classified the studies as short-term and midterm follow-up.
Nineteen randomized controlled trials involving 4516 cases were identified. Compared with anterior cervical decompression and fusion, cervical total disc replacement had better functional outcomes (neck disability index NDI, NDI success, neurological success, neck pain scores reported on a numerical rating scale NRS, visual analog scales scores and overall success), greater segmental motion at the index level, fewer adverse events and fewer secondary surgical procedures at the index and adjacent levels in short-term follow-up (P < 0.05). With midterm follow-up, the cervical total disc replacement group indicated superiority in the NDI, neurological success, pain assessment (NRS), and secondary surgical procedures at the index level (P < 0.05). The Short Form 36 (SF-36) and segmental motion at the adjacent level in the short-term follow-up showed no significant difference between the two procedures, as did the secondary surgical procedure rates at the adjacent level with midterm follow-up (P > 0.05).
Cervical total disc replacement presented favorable functional outcomes, fewer adverse events, and fewer secondary surgical procedures. The efficacy and safety of cervical total disc replacement are superior to those of fusion. Longer-term, multicenter studies are required for a better evaluation of the long-term efficacy and safety of the two procedures.
Cerebrospinal fluid (CSF) in the paravascular spaces of the surface arteries (sPVS) is a vital pathway in brain waste clearance. Arterial pulsations may be the driving force of the paravascular flow, ...but its pulsatile pattern remains poorly characterized, and no clinically practical method for measuring its dynamics in the human brain is available. In this work, we introduce an imaging and quantification framework for in-vivo non-invasive assessment of pulsatile fluid dynamics in the sPVS. It used dynamic Diffusion-Weighted Imaging (dDWI) at a lower b-values of 150s/mm2 and retrospective gating to detect the slow flow of CSF while suppressing the fast flow of adjacent arterial blood. The waveform of CSF flow over a cardiac cycle was revealed by synchronizing the measurements with the heartbeat. A data-driven approach was developed to identify sPVS and allow automatic quantification of the whole-brain fluid waveforms. We applied dDWI to twenty-five participants aged 18-82 y/o. Results demonstrated that the fluid waveforms across the brain showed an explicit cardiac-cycle dependency, in good agreement with the vascular pumping hypothesis. Furthermore, the shape of the CSF waveforms closely resembled the pressure waveforms of the artery wall, suggesting that CSF dynamics is tightly related to artery wall mechanics. Finally, the CSF waveforms in aging participants revealed a strong age effect, with a significantly wider systolic peak observed in the older relative to younger participants. The peak widening may be associated with compromised vascular compliance and vessel wall stiffening in the older brain. Overall, the results demonstrate the feasibility, reproducibility, and sensitivity of dDWI for detecting sPVS fluid dynamics of the human brain. Our preliminary data suggest age-related alterations of the paravascular pumping. With an acquisition time of under six minutes, dDWI can be readily applied to study fluid dynamics in normal physiological conditions and cerebrovascular/neurodegenerative diseases.
We present the results of a search for weakly interacting massive particles (WIMPs) from the commissioning run of the PandaX-II experiment located at the China Jinping Underground Laboratory. A WIMP ...search data set with an exposure of 306x19.1kg-day was taken, while its dominant Kr super(85) background was used as the electron recoil calibration. No WIMP candidates are identified, and a 90% upper limit is set on the spin-independent elastic WIMP-nucleon cross section with a lowest excluded cross section of 2.97x10 super(-45)cm super(2) at a WIMP mass of 44.7GeV/c super(2).
Lactose maldigesters report an increase in abdominal pain due to the consumption of milk containing a mixture of A1 and A2 β-casein as compared to milk containing only A2 β-casein. Gastric transit ...affects gastrointestinal symptoms and rapid transit has been associated with an increase in abdominal pain. We conducted a double-blinded, randomized, crossover trial in 10 lactose maldigesters. Subjects consumed each of the two types of milk: conventional milk containing 75% A1 β-casein and 25% A2 β-casein and A2 milk containing 100% A2 β-casein. Magnetic resonance images were acquired, and abdominal pain was rated and recorded at 0, 10, 30, 60 and 120 min after milk consumption. The volume of milk in the stomach was calculated using FSL software. The volume of milk in the stomach after consuming milk with 75% A1 β-casein and 25% A2 β-casein was significantly lower at 30 (
= 0.01), 60 (
= 0.002) and 120 (
< 0.001) minutes as compared to milk with 100% A2 β-casein in the 10 lactose maldigesters. The transit of New-World milk containing A1 and A2 β-casein was more rapid as compared to Old-World milk containing only A2 β-casein. This difference in transit may mediate symptoms of lactose intolerance.
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