Mesenchymal stem cells (MSCs) confer therapeutic benefits in various pathologies and cancers by releasing extracellular vesicles (EVs) loaded with bioactive compounds. Herein, we identified bone ...marrow MSC (BMSC)-derived EVs harboring microRNA (miR)-29b-3p to regulate osteogenic differentiation through effects on the suppressor of cytokine signaling 1 (SOCS1)/nuclear factor (NF)-κB pathway
targeting of lysine demethylase 5A (KDM5A) in osteoporosis.
We quantified the miR-29b-3p in BMSC-derived EVs from bone marrow specimens of osteoporotic patients and non-osteoporotic patients during total hip arthroplasty (THA). miR-29b-3p targeting KDM5A was confirmed by promoter luciferase assay, and enrichment of KDM5A in the promoter region of SOCS1 was analyzed by chromatin immunoprecipitation (ChIP). The expression and translocation of NF-κB to the nucleus were detected by western blot analysis and immunofluorescence staining, respectively. An ovariectomized (OVX) osteoporosis mouse model was established to further confirm the
findings.
BMSC-derived EVs of osteoporotic patients exhibited downregulated miR-29b-3p. EV-encapsulated miR-29b-3p from BMSCs potentiated osteogenic differentiation by specifically inhibiting KDM5A. KDM5A inhibited osteogenic differentiation by the regulation of H3K4me3 and H3K27ac of SOCS1. SOCS1 potentiated osteogenic differentiation by inhibiting NF-κB pathway.
EV-encapsulated miR-29b-3p derived from BMSCs potentiated osteogenic differentiation through blockade of the SOCS1/NF-κB pathway by inhibition of KDM5A.
In this study, the concentrations of seven heavy metals (Cr, Ni, Cu, Zn, As, Hg, and Pb) and Pb isotope in a sediment core from the Shuanglong reservoir, Southwestern China, were investigated. Based ...on the constant rate of supply (CRS) model, the age span of a 60 cm sediment sample was determined to range from the years 1944 to 2015. Combined with chronology and heavy metal content, the evolution of the sources and pollution levels of heavy metals showed a changing trend composed of various stages. The sources of heavy metals transitioned from natural origins in 1944–1964 to industrial origins in 1965–2004. The subsequent reduction in heavy metal content was mainly due to the vigorous implementation of environmental protection policies from 2005 to 2012. In recent years (2013–2015), the heavy metal content has increased due to frequent human activity. Principal component analysis (PCA), correlation analysis, and the coefficient of variation (CV) analysis indicated that Cr, Ni, Cu, Zn, and As were derived from natural processes, Pb mainly came from automobile manufacturing, and Hg was mainly from industrial sources. The values of the geo-accumulation index (Ig), single pollution index (Pi), and single potential ecological risk index (Er) showed that the contamination of Hg and Pb was slight to moderate. Moreover, the values of the potential ecological risk index (RI), pollution load index (PLI), and Nemerow index (PN) indicated that the Shuanglong reservoir is under low ecological risk.
Abstract Objective Smooth muscle cells (SMCs) death promotes atherosclerotic lesion necrosis and plaque destabilization. We investigated the potential mechanisms of rat SMCs death in response to ...excess free cholesterol (FC). Methods and results Rat aortic SMCs were incubated with “water soluble cholesterol” and acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor Sandoz58035 to establish FC-overloading cell model. Disruption of mitochondrial network and endoplasmic reticulum (ER) was observed after 12 h incubation by transient transfection. After treated for 24 h, enhanced cell death was noted as detected by propidium iodide (PI) staining/flow cytometry ( P < 0.001 vs. control). SMCs death was associated with markedly decreased mitochondrial transmembrane potential (Δ φ m), as well as upregulation of cellular reactive oxygen species (ROS) and ER stress. We also investigated possible signaling pathways involved in excess FC-initiated cell death and found that unfolded protein response (UPR) was activated, with increased cellular Bax expression and release of mitochondrial cytochrome c. Conclusion Our findings suggested that FC-overloading might trigger SMCs death. Both ER- and mitochondria-based signals might be implicated in these lethal events.
Simple sequence repeat (SSR) markers were developed from expressed sequence tags (ESTs) in the eastern oyster (Crassostrea virginica). ESTs of the eastern oyster were downloaded from GenBank and ...screened for SSRs with at least eight units of dinucleotide or five units of tri-, tetra-, penta-, and hexa-nucleotide repeats. The screening of 9101 ESTs identified 127 (1.4%) SSR-containing sequences. Primers were designed for 88 SSR-containing ESTs with good and sufficient flanking sequences. Polymerase chain reaction (PCR) amplification was successful for 71 primer pairs, including 19 (27%) pairs that amplified fragments longer than expected sizes, probably due to introns. Sixty-six pairs that produced fragments shorter than 800 bp were screened for polymorphism in five oysters from three populations via polyacrylamide gels, and 53 of them (80%) were polymorphic. Fifty-three polymorphic SSRs were labeled and genotyped in 30 oysters from three populations via an automated sequencer. Five of the SSRs amplified more than two fragments per oyster, suggesting locus duplication. The remaining 48 SSRs had 2 alleles per individual, including 11 with null alleles. In the 30 oysters analyzed, the SSRs had an average of 9.3 alleles per locus, ranging from 2 to 24. Forty-three loci segregated in a family with 100 progeny, with nine showing significant deviation from Mendelian ratios (three after Bonferroni correction). Seventy percent of the loci were successfully amplified in C. rhizophorae and 34% in C. gigas. This study demonstrates that ESTs are valuable resources for the development of SSR markers in the eastern oyster, and EST-derived SSRs are more transferable across species than genomic SSRs.
Plastic film mulching (PM) is widely utilized for maize production in China. However, the effect of PM on the grain yield of crops has not been established, and the biochemical mechanism underlying ...the increase or decrease in grain yield under PM is not yet understood. Grain filling markedly affects the grain yield. The objective of this study was to investigate the effects of PM on maize grain filling under different irrigation levels and the relationship of such effects with hormonal changes. In the present study, PM was compared with traditional nonmulching management (TN) under 220 mm, 270 mm and 320 mm irrigation amount, and the grain filling characters of the grains located in various parts of the ear and the hormonal changes in the grains were measured. The results indicated that at 220 mm irrigation, PM significantly increased the grain filling rate of the middle and basal grains and decreased the grain filling rate of the upper grains. At 270 mm irrigation, the PM significantly increased the grain filling rate of the all grains. At 320 mm irrigation, the PM only significantly increased the grain filling rate of the upper grains. The IAA, Z+ZR and ABA content in the grains was positively correlated with the grain weight and grain-filling rates; however, the ETH evolution rate of the grains was negatively correlated with the grain weight and grain-filling rates. These results show that the effect of PM on maize grain filling is related to the irrigation amount and that the grain position on the ear and the grain filling of the upper grains was more sensitive to PM and irrigation than were the other grains. In addition, the PM and irrigation regulated the balance of hormones rather than the content of individual hormones to affect the maize grain filling.
The thermal structure of the environmental atmosphere associated with Terrestrial Gamma-ray Flashes (TGFs) is investigated with the combined observations from several detectors (FERMI, RHESSI, and ...Insight-HXMT) and GNSS-RO (SAC-C, COSMIC, GRACE, TerraSAR-X, and MetOp-A). The geographic distributions of TGF-related tropopause altitude and climatology are similar. The regional TGF-related tropopause altitude in Africa and the Caribbean Sea is 0.1–0.4 km lower than the climatology, whereas that in Asia is 0.1–0.2 km higher. Most of the TGF-related tropopause altitudes are slightly higher than the climatology, while some of them have a slightly negative bias. The subtropical TGF-producing thunderstorms are warmer in the troposphere and have a colder and higher tropopause over land than the ocean. There is no significant land–ocean difference in the thermal structure for the tropical TGF-producing thunderstorms. The TGF-producing thunderstorms have a cold anomaly in the middle and upper troposphere and have stronger anomalies than the deep convection found in previous studies.
Adversarial examples can evade the detection of text classification models based on Deep Neural Networks (DNNs), thus posing a potential security threat to the system. To address this problem, we ...propose an adversarial example defense method for Chinese text classification called WordRevert. The method first obtains the "positive text" containing the adversarial words by filtering the clauses that do not contribute to the current classification label. Then the detection network is combined with the position importance calculation function to achieve the detection of the adversarial words. Finally, the adversarial words are restored to the original words by calculating the candidate score and the detection score. The experiments show that the current popular Chinese text adversarial attack algorithms can be effectively defended by this method, and achieve a significant increase in the accuracy of the adversarial examples with a small reduction in the classification accuracy of clean samples while achieving better precision, recall, and F1 value of adversarial word detection and restoration.
To observe the clinical and imaging characteristics of radiation-induced optic neuropathy (RION).
We retrospectively reviewed the clinical data of 43 patients (69 eyes) who were diagnosed with RION ...at the Chinese PLA General Hospital from 2010 to 2021.
The latency from radiotherapy to onset of visual loss ranged from 1 to 132 (36.33 ± 30.48) months. Optic disc pallor and optic disc edema were found in 27.0% (10/37) and 8.1% (3/37) of the eyes, respectively, within 2 months. After treatment, the best corrected visual acuity (BCVA) was restored in 24.6% (17/69) of the eyes and the final BCVA improved in 13.0% (9/69) of the eyes. An 82.5% (33/40) of the eyes with magnetic resonance imaging (MRI) showed enhancement of the affected optic nerve, mostly (69.7%) in the intracranial segment, and 36.4% (12/33) of the eyes with expansion and T2-high signals also showed enhancement of the affected optic nerve. The superior retinal nerve fiber layer (RNFL) and the outer circle superior quadrant (OS) of the inner limiting membrane to retinal pigment epithelium (ILM-RPE) layer thinned significantly during the first month. The center of the ILM-RPE layer thickened significantly during the first two months and the inner circle temporal quadrant (IT) of the ILM-RPE layer thickened significantly from the third to sixth month. The RNFL thinned significantly after 6 months except for the temporal quadrant, and the average inner circle superior quadrant (IS) and outer circle of the ILM-RPE layer thinned significantly after 6 months. There was no significant difference between hyperbaric oxygen therapy (HBOT) and high-dose intravenous methylprednisolone (IVMP) therapy in improving BCVA recovery or final BCVA (P > 0.05).
The structural damage of the RNFL and ILM-RPE layer occurred during the first month, the RNFL showed progressive thinning during the follow-up period, while the ILM-RPE layer showed thinning during the first month, thickening from the third to sixth month, and thinning after 6 months. There was a discrete region of enhancement of the optic nerve, often with expansion and high-T2 signals on MRI. HBOT and high-dose IVMP therapy were hardly effective for treating RION in the non-acute stage.
Introduction
The aim of this study was to determine the effect of a new type of Mg-3Nd-1Gd-0.3Sr-0.2Zn-0.4Zr (abbreviated to Mg-Nd-Gd-Sr) alloy on bone marrow mesenchymal stem cell (BMSCs) function ...derived from SD rats.
Methods
BMSCs were first isolated and cultured in vitro using the whole bone marrow adherence method, and identified by BMSC surface biomarkers and osteogenic induction. The in vitro biological safety of the Mg-Nd-Gd-Sr alloy was studied by cytotoxicity and apoptosis experiments, and the in vitro biological functions were studied by cell adhesion and cell proliferation experiments.
Results
The results showed that high-purity BMSCs were isolated using the whole bone marrow adherence method. Flow cytometry showed high expression of CD44 and CD90, and low expression of CD31 and CD45 in the BMSCs. Osteogenic induction showed that the BMSCs differentiated into osteoblasts, and mineralized nodules were observed. The cytotoxicity of the Mg-Nd-Gd-Sr alloy to SD rat BMSCs was 0–1 grade, suggesting that the Mg-Nd-Gd-Sr alloy had no significant cytotoxic effect on SD rat BMSCs; compared with the control group, there was no significant cell apoptosis in any of the experimental groups (p > 0.05). Cell adhesion experiments showed that the number of adherent cells increased with the duration of culture with the exception of the 100% concentration group; compared with the control group, the 75% concentration group had the highest number of adherent cells at the 1st, 3rd, 5th, and 7th hours (p < 0.05). Cell proliferation experiments showed that the number of cells in all experiment groups was higher than the control group (p < 0.05) on the 1st, 3rd, 5th, and 7th days, with the highest number of cells in the 75% concentration group (p < 0.05).
Conclusion
Our data indicate that the extracts of new type of Mg-Nd-Gd-Sr alloy has no apparent cytotoxicity to BMSCs, does not affect cell apoptosis, and has good biocompatibility. Different concentrations of Mg-Nd-Gd-Sr alloy extracts promoted the adhesion and proliferation of BMSCs. The alloy had good biological functions, and is thus a promising bone repair material.
PDF
