Extracellular vesicles (EVs) derived from human umbilical cord mesenchymal stem cells (hUCMSCs) have emerged as promising candidates for cell-free therapy in various diseases, including chronic ...cutaneous wounds. However, the lack of standardized protocols for EVs’ preparation and identification poses a significant challenge to their clinical application. Thus, the objective was to develop a safe and efficient method for the large-scale production of hUCMSC-derived EVs while establishing a comprehensive identification protocol encompassing morphology, particle size distribution, protein expression, and purity. This study observed that most of the EVs acquired through the protocol exhibited either a cup-shaped or round-shaped structure, with a median diameter of ~73.25 nm. The proportions of EVs positive for CD9, CD63, and CD81 were 37.5%, 38.6%, and 19.8%, respectively. To enhance their therapeutic potential in wound treatment, EVs were incorporated into chitosan hydrogel, forming chitosan hydrogel-EVs (CS-EVs). Furthermore, it was demonstrated that CS-EVs exhibited continuous release of EVs into the surrounding environment and, importantly, that the released EVs were internalized by human umbilical vein endothelial cells (HUVECs), resulting in significant enhancement of cell migration and angiogenesis. Additionally, in a rat model of diabetic foot ulcers, CS-EVs demonstrated a robust therapeutic effect in promoting wound healing. Following a 15-day treatment period, the group treated with CS-EVs demonstrated an impressive 93.3% wound closure ability, accompanied by a high degree of re-epithelialization. In contrast, the control group exhibited only a 71.5% reduction in wound size. In summary, this study offers solutions for the purification, characterization, and application of EVs in clinical wound treatment. These results not only offer fresh perspectives on the involvement of hUCMSC-derived EVs in wound healing but also introduce a non-invasive approach for applying EVs that holds practical significance in skin repair.
Graphical Abstract
Pneumoconiosis is one of the most serious occupational diseases worldwide. Silicosis due to prolonged inhalation of free silica dust during occupational activities is one of the main types. ...Cuproptosis is a newly discovered mode of programmed cell death characterized by the accumulation of free copper in the cell, which ultimately leads to cell death. Increased copper in the serum of silicosis patients, suggests that the development of silicosis is accompanied by changes in copper metabolism, but whether cuproptosis is involved in the progression of silicosis is actually to be determined. To test this hypothesis, we screened the genetic changes in patients with idiopathic fibrosis by bioinformatics methods and predicted and functionally annotated the cuproptosis-related genes among them. Subsequently, we established a mouse silicosis model and detected the concentration of copper ions and the activity of ceruloplasmin (CP) in serum, as well as changes of the concentration of copper and cuproptosis related genes in mouse lung tissues. We identified 9 cuproptosis-related genes among the differential genes in patients with IPF at different times and the tissue-specific expression levels of ferredoxin 1 (FDX1) and Lipoyl synthase (LIAS) proteins. Furthermore, serum CP activity and copper ion levels in silicosis mice were elevated on days 7th and 56th after silica exposure. The expression of CP in mouse lung tissue elevated at all stages after silica exposure. The mRNA level of FDX1 decreased on days 7th and 56th, and the protein level remained in accordance with the mRNA level on day 56th. LIAS and Dihydrolipoamide dehydrogenase (DLD) levels were downregulated at all times after silica exposure. In addition, Heatshockprotein70 (HSP70) expression was increased on day 56. In brief, our results demonstrate that there may be cellular cuproptosis during the development of experimental silicosis in mice and show synchronization with enhanced copper loading in mice.
•Elevated level of copper loading during the development of experimental silicosis.•The level of cuproptosis indicators changes synchronously with serum copper.•Cellular cuproptosis may exist in each phase of silicosis.
In this paper, a novel solar driven smoke ventilation system was proposed for the moxibustion therapy. A mathematical model is developed based on heat balance and fluid flow, and the performance of ...the ventilation system is studied. Sensitivity analyses of solar radiation intensity from 100 to 1000 W/m2, collector length from 1 to 10 m, solar system width from 0.5 to 3 m, and chimney width from 0.1 to 0.3 m, and chimney height from 0.5 to 3 m are also performed. For stronger solar radiation, larger collector or higher chimney, the effective heat flux of the solar system increases and the flow rate increases. For the solar radiation of larger than 210 W/m2, the velocity at the smoke pipe entrance is larger than the critical velocity of 0.5 m/s. Higher chimney also leads to the increase of the driving force besides receiving more solar radiation. For reaching the pipe entrance velocity of larger than the critical velocity, a solar radiation of larger than 210 W/m2, a chimney height of higher than 0.89 m, a collector length of larger than 1.9 m, or a collector width of larger than 0.198 m is needed. The conclusions are obtained under the absent parametric values: the solar radiation intensity of 600 W/m2, the chimney height of 2 m, the solar collector length of 8 m, and the widths of solar collector and chimney of 0.25 m. This work lays a solid foundation for application of this solar driven smoke ventilation system to the moxibustion therapy.
Clay-abundant shale formations are quite common worldwide shale plays. This particular type of shale play has unique physico-chemical characteristics and therefore responds uniquely to the gas ...storage and production process. Clay minerals have huge surface areas due to prevailing laminated structures, and the deficiency in positive charges in the combination of tetrahedral and octahedral sheets in clay minerals produces strong cation exchange capacities (CECs), all of which factors create huge gas storage capacity in clay-abundant shale formations. However, the existence of large amounts of tiny clay particles separates the contacts between quartz particles, weakening the shale formation and enhancing its ductile properties. Furthermore, clay minerals’ strong affinity for water causes clay-abundant shale formations to have large water contents and therefore reduced gas storage capacities. Clay-water interactions also create significant swelling in shale formations. All of these facts reduce the productivity of these formations. The critical influences of clay mineral-water interaction on the productivity of this particular type of shale plays indicates the inappropriateness of using traditional types of water-based fracturing fluids for production enhancement. Non-water-based fracturing fluids are therefore preferred, and CO2 is preferable due to its many unique favourable characteristics, including its minor swelling effect, its ability to create long and narrow fractures at low breakdown pressures due to its ultralow viscosity, its contribution to the mitigation of the greenhouse gas effect, rapid clean-up and easy residual water removal capability. The aim of this paper is to obtain comprehensive knowledge of utilizing appropriate production enhancement techniques in clay-abundant shale formations based on a thorough literature review.
Blast lung injuries (BLIs) are frequent because of industrial accidents and terrorist groups. Bone marrow mesenchymal stem cells (BMSCs) and exosomes derived from BMSCs (BMSCs-Exo) have become a hot ...topic in modern biology because of their significance in damage healing, immune regulation, and gene therapy. The aim of this study is to investigate the effect of BMSCs and BMSCs-Exo on BLI in rats caused by gas explosion. Here, BMSCs and BMSCs-Exo were transplanted into BLI rats via tail vein and then evaluated pathological alterations, oxidative stress, apoptosis, autophagy, and pyroptosis in the lung tissue. Through histopathology and changes in malondialdehyde (MDA) and superoxide dismutase (SOD) contents, we discovered that oxidative stress and inflammatory infiltration in the lungs were significantly reduced by BMSCs and BMSCs-Exo. After treatment with BMSCs and BMSCs-Exo, apoptosis-related proteins, such as cleaved caspase-3 and Bax, were significantly decreased, and the ratio of Bcl-2/Bax was significantly increased; the level of pyroptosis-associated proteins, including NLRP3, GSDMD-N, cleaved caspase-1, IL-1β, and IL-18, were decreased; autophagy-related proteins, beclin-1 and LC3, were downregulated while P62 was upregulated; the number of autophagosomes was decreased. In summary, BMSCs and BMSCs-Exo attenuate BLI caused by gas explosion, which may be associated with apoptosis, aberrant autophagy, and pyroptosis.
Abstract
The formation of the first supermassive black holes is expected to have occurred in some most pronounced matter and galaxy overdensities in the early universe. We have conducted a ...submillimeter wavelength continuum survey of 54
z
∼ 6 quasars using the Submillimeter Common-User Bolometre Array-2 on the James Clerk Maxwell Telescope to study the environments around
z
∼ 6 quasars. We identified 170 submillimeter galaxies (SMGs) with above 3.5
σ
detections in 450 or 850
μ
m maps. Their far-IR luminosities are (2.2–6.4) × 10
12
L
⊙
, and their star formation rates are ∼400–1200
M
⊙
yr
−1
. We also calculated the SMGs’ differential and cumulative number counts in a combined area of ∼620 arcmin
2
. To a 4
σ
detection (at ∼5.5 mJy), SMGs’ overdensity is
0.68
−
0.19
+
0.21
(±0.19), exceeding the blank-field source counts by a factor of 1.68. We find that 13/54 quasars show overdensities (at ∼5.5 mJy) of
δ
SMG
∼ 1.5–5.4. The combined area of these 13 quasars exceeds the blank-field counts with the overdensity to 5.5 mJy of
δ
SMG
∼
2.46
−
0.55
+
0.64
(±0.25) in the regions of ∼150 arcmin
2
. However, the excess is insignificant on the bright end (e.g., 7.5 mJy). We also compare results with previous environmental studies of Ly
α
emitters and Lyman break galaxies on a similar scale. Our survey presents the first systematic study of the environment of quasars at
z
∼ 6. The newly discovered SMGs provide essential candidates for follow-up spectroscopic observations to test whether they reside in the same large-scale structures as the quasars and search for protoclusters at an early epoch.
Because the limitations of water-based fracturing fluids restrict their fracturing efficiency and scope of application, liquid CO2 is regarded as a promising substitute, owing to its unique ...characteristics, including its greater environmental friendliness, shorter clean-up time, greater adsorption capacity than CH4 and less formation damage. Conversely, the disadvantage of high leak-off rate of CO2 fracturing due to its very low viscosity determines its applicability in gas shales with ultra-low permeability, accurate measurement of shale permeability to CO2 is therefore crucial to evaluate the appropriate injection rate and total consumption of CO2. The main purpose of this study is to accurately measure shale permeability to CO2 flow during hydraulic fracturing, and to compare the leak-off of CO2 and water fracturing. A series of permeability tests was conducted on cylindrical shale samples 38 mm in diameter and 19 mm long using water, CO2 in different phases and N2 considering multiple influencing factors. According to the experimental results, the apparent permeability of shale matrix to gaseous CO2 or N2 is greatly over-estimated compared with intrinsic permeability or that of liquid CO2 due to the Klinkenberg effect. This phenomenon explains that the permeability values measured under steady-state conditions are much higher than those under transient conditions. Supercritical CO2 with higher molecular kinetic energy has slightly higher permeability than liquid CO2. The leak-off rate of CO2 is an order of magnitude higher than that of water under the same injection conditions due to its lower viscosity. The significant decrease of shale permeability to gas after water flooding is due to the water block effect, and much longer clean-up time and deep water imbibition depth greatly impede the gas transport from the shale matrix to the created fractures. Therefore, it is necessary to substitute water-based fracturing fluids with liquid or super-critical CO2 in clay-abundant shale formations.
Hedyotis diffusa Willd (Rubiaceae) is a widely used and resourceful traditional Chinese medicine that exerts protection against aging and age‐related diseases. However, the underlying mechanisms of ...the protective effects remain largely unclear. Alzheimer's disease (AD) is an age‐related neurodegenerative disease, of which β‐amyloid (Aβ)‐induced toxicity has been suggested as a main cause. Herein, we use the transgenic Caenorhabditis elegans CL4176, CL2006, and CL2355 strains, which express human Aβ1‐42 peptide, to investigate the effects and the possible mechanisms of n‐butanol extract of H.diffusa (HDB)‐mediated protection against Aβ toxicity in vivo. During the experiments, a method of quality control for HDB was established by HPLC. Additionally, we examined the effects of HBD on gene expression changes with qRT‐PCR, aggregation of Aβ plagues with thioflavin‐S staining, and protein detection with GFP labeling. HDB improved lifespan, locomotion, and stress resistance. Further study showed that HDB decreased paralysis, the accumulation of ROS, and AChE activity. Moreover, HDB suppressed neuronal Aβ‐expression‐induced defects in chemotaxis behavior and increased SOD activity. HDB also downregulated the Aβ mRNA level and decreased the number of Aβ deposits. Furthermore, HDB increased the expression levels of sod‐3, daf‐16, hsf‐1, and hsp‐16.2 gene and upregulated hsp‐16.2::GFP and gst‐4::GFP expression. Taken together, these results suggest that HDB may protect against Aβ‐induced toxicity in C. elegans via the insulin/insulin‐like growth factor‐1 (IGF‐1) signaling pathway.
It is crucial to investigate the characteristics of meteorological drought in the Beijing–Tianjin–Hebei (BTH) region to improve the accuracy of agriculture and water resource monitoring and ...management. In this study, using instrumental observation data from 85 meteorological stations in the BTH region during 1961–2023 derived from the National Meteorological Information Center, we first calculated the meteorological drought comprehensive index (MCI) and analyzed the spatiotemporal characteristics of the MCI. In the BTH region, the MCI intensity from May to June was the most severe in the intraseasonal variation. The trend of the decreasing drought intensity in May–June has occurred for the past 60 years. The southern region in the BTH region was more likely to experience droughts. Next, the spatial patterns of the top two EOF modes of the May–June MCI were depicted. The primary spatial pattern of the BTH, which was characterized by consistent changes in the MCI throughout the entire BTH region, could be represented by the first mode’s R2 of 69.01%. Then, we compared the spatial pattern of the MCI intensity under different return periods. Using the May–June MCI of 1961–2023, the drought intensity gradually increased from northwest to southeast for the 10-, 20-, and 50-year return periods. However, the drought intensity decreased and then increased from northwest to southeast based on the 1991–2023 MCI. Notably, a 20-year return period of severe drought affected Beijing and northern Hebei in 2023. Finally, we discussed the linkages of drought in the BTH region and atmospheric circulation/sea surface temperature (SST) anomalies, which were calculated using the Pearson correlation coefficient and wavelet coherence. We suggest that the MCI variations in the BTH region may be related to the SST anomalies of the Indian Ocean in 1961–1990 and the Pacific Ocean in 1991–2023, respectively. The abovementioned studies have enlightened us to focus on predicting the Pacific SST for drought, which will facilitate agricultural production and water resource management in the BTH region.
The influence of water on the mechanical properties of rocks has been observed by many researchers in rock engineering and laboratory tests, especially for sedimentary rocks. In order to investigate ...the effect of water saturation on the mechanical properties of low-permeability rocks, uniaxial compression tests were conducted on siltstone with different water contents. The effects of water on the strength, elastic moduli, crack initiation and damage thresholds were observed for different water saturation levels. It was found that 10% water saturation level caused more than half of the reductions in mechanical properties. A new approach is proposed to analyze the stress-strain relations at different stages of compression by dividing the axial and lateral stress-strain curves into five equal stress zones, where stress zones 1-5 refer to 0%-20%, 20%-40%, 40%-60%, 60%-80% and 80%-100% of the peak stress, respectively. Stress zone 2 represents the elastic range better than stress zone 3 which is at half of the peak stress. The normalized crack initiation and crack damage stress thresholds obtained from the stress-strain curves and acoustic emission activities averaged 31.5% and 83% of the peak strength respectively. Pore pressure is inferred to take part in the deformation of low-permeability siltstone samples, especially at full saturation levels. A change of failure pattern from multi-fracturing to single shear failure with the increase of water saturation level was also observed.
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