Enhancer-mediated FOXO3 expression promotes MSC adipogenic differentiation by activating autophagy.

BACKGROUND: Mesenchymal stem cells (MSCs) are pluripotent stem cells capable of differentiating into osteocytes, adipocytes and chondrocytes. However, in osteoporosis, the balance of differentiation is tipped toward adipogenesis and the key mechanism is controversial. Researches have shown that, as upstream regulatory elements of gene expression, enhancers ar involved in the expression of identity genes. In this study, we identified enhancers-mediated gene FOXO3 promoting MSC adipogenic differentiation by activating autophagy. METHODS: We integrated data of RNA sequencing (RNA-seq), chromatin immunoprecipitation sequencing (ChIP-seq) and ATAC-sequencing (ATAC-seq) to find the identity gene FOXO3. The expression of FOXO3 protein, adipogenic transcription factors and the substrate of autophagy were measured by western blotting. The Oil Red O (ORO) staining was used to visualize the adipogenesis of MSCs. Immunohistochemistry was used to visualize the FOXO3 expression in adipocytes in bone marrow. Immunofluorescence was used to detect the expression of PPARγ and LC3B. RESULTS: During adipogenesis, enhancers redistribute to genes associated with adipogenic differentiation, among which we identified the pivotal identity gene FOXO3. FOXO3 could promote the expression of the adipogenic transcription factors PPARγ, CEBPα, and CEBPß during adipogenic differentiation, while PPARγ, CEBPα, and CEBPß could in turn bind to FOXO3 and continue to promote FOXO3 expression to form a positive feedback loop. Consistently elevated FOXO3 expression promotes autophagy by activating the PI3K-AKT pathway which mediates adipogenic differentiation. CONCLUSIONS: Pivotal identity gene FOXO3 promotes autophagy by activating PI3K-AKT pathway, which provokes adipogenic differentiation of MSCs. Enhancer-regulated adipogenic identity gene FOXO3 could be an attractive treatment for osteoporosis.

Characterization of atmospheric mercury from mercury-added product manufacturing using passive air samplers.

Although alternatives to mercury (Hg) are available in most products and industrial activities, Hg continues to be an ingredient in some products, including fluorescent lamps and electrical and electronic equipment (EEE). In this work, low-cost passive air samplers (PASs) were used to investigate the atmospheric Hg pollution in Zhongshan, a large industrial city and major hub of mercury-added product manufacturing in South China. The GEM concentrations in the atmosphere were measured for two weeks during the summer of 2019 at a total of 144 sites across Zhongshan. Comparison with the results of active sampling confirmed that the PASs yielded accurate and reliable gaseous elemental mercury (GEM) concentrations and were thus well-suited for multi-site field monitoring. The mean GEM concentrations in the areas with mercury-added product manufacturing activities (5.1 ± 0.4 ng m-3) were significantly higher than those in other parts of Zhongshan (1.5 ± 0.4 ng m-3), indicating that local releases, rather than regional transport, were responsible for the atmospheric Hg pollution. Elevated GEM concentrations (up to 11.4 ng m-3) were found in the vicinity of fluorescent lamp and EEE factories and workshops, indicating significant Hg vapor emissions, presumably from the outdated production technologies and non-standard operation by under-trained workers. The Hg emissions from mercury-added product manufacturing were estimated to be 0.06 and 7.8 t yr-1 for Zhongshan and China, respectively, based on the scales of fluorescent lamp and EEE production. The non-carcinogenic health risk of Zhongshan residents from inhalation and ingestion was judged acceptable, whereby the inhalation exposure in Hg-polluted areas exceeded that of dietary ingestion. These findings demonstrate that mercury-added product manufacturing still contributes notably to anthropogenic gaseous Hg releases in the industrial areas with intense mercury-added product manufacturing activities.

The m6A methyltransferase METTL16 negatively regulates MCP1 expression in mesenchymal stem cells during monocyte recruitment.

Mesenchymal stem cells (MSCs) possess strong immunoregulatory functions, one aspect of which is recruiting monocytes from peripheral vessels to local tissue by secreting monocyte chemoattractant protein 1 (MCP1). However, the regulatory mechanisms of MCP1 secretion in MSCs are still unclear. Recently, the N6-methyladenosine (m6A) modification was reported to be involved in the functional regulation of MSCs. In this study, we demonstrated that methyltransferase-like 16 (METTL16) negatively regulated MCP1 expression in MSCs through the m6A modification. Specifically, the expression of METTL16 in MSCs decreased gradually and was negatively correlated with the expression of MCP1 after coculture with monocytes. Knocking down METTL16 markedly enhanced MCP1 expression and the ability to recruit monocytes. Mechanistically, knocking down METTL16 decreased MCP1 mRNA degradation, which was mediated by the m6A reader YTH N6-methyladenosine RNA-binding protein 2 (YTHDF2). We further revealed that YTHDF2 specifically recognized m6A sites on MCP1 mRNA in the CDS region and thus negatively regulated MCP1 expression. Moreover, an in vivo assay showed that MSCs transfected with METTL16 siRNA showed greater ability to recruit monocytes. These findings reveal a potential mechanism by which the m6A methylase METTL16 regulates MCP1 expression through YTHDF2-mediated mRNA degradation and suggest a potential strategy to manipulate MCP1 expression in MSCs.

Recent Progress on In Situ/Operando Characterization of Rechargeable Alkali Ion Batteries.

The specific chemical and physical evolutions of electrode materials under operating conditions should be understood to optimize their electrochemical performances. The in-situ/operando techniques including Raman spectrum, transmission electron microscope, X-ray diffraction, X-ray absorption spectrum, and magnetization are powerful tools, which can provide the real-time surficial/interfacial changes of electrodes, the transformation of crystal lattice structures, the adjustment of electronic states and even the influence of magnetic properties under operating conditions. In this Review, the advantages and limitations of these in-situ/operando techniques in investigating the inner energy storage mechanisms of various type electrode materials are analyzed. The representative research results such as the ion dependent storage mechanism, step-alloying processes and space charge storage theory are highlighted. In addition, the challenges and opportunities of in-situ/operando characterizations are proposed as well.

Atmospheric mercury pollution caused by fluorescent lamp manufacturing and the associated human health risk in a large industrial and commercial city.

Although already eliminated in most industrial processes, mercury, as an essential ingredient in all energy-efficient lighting technologies, is still used in fluorescent lamp manufacturing. This study was conducted to investigate the atmospheric pollution caused by fluorescent lamp production and assess the associated public health risk in a large industrial and commercial city of south China, Zhongshan, which is a major production hub of lighting products. Concentrations of total gaseous mercury (TGM) in the atmosphere were measured over a total of 342 sites in the industrial, commercial, and residential areas. The average levels of TGM in the industrial, commercial, and residential areas prior to the landing of a typhoon were 12 ± 11, 3.6 ± 2.1, and 2.7 ± 1.3 ng⋅m-3, respectively. TGM concentrations in the industrial areas exhibited significant diurnal variation, with levels in the working hours being much higher than those in the non-working hours, which indicates that the high atmospheric mercury concentrations were contributed by local emissions, instead of regional transport. Most fluorescent lamp manufacturing activities in the city were shut down during a typhoon event, which resulted in a significant reduction in the average TGM level (down to 1.6 ± 1.8 ng⋅m-3) and rendered the difference in the average TGM levels in the industrial areas no longer significant between the working and non-working hours. Elevated TGM levels (up to 49 ng⋅m-3) were found near clusters of small-scale fluorescent lamp workshops in both industrial and commercial areas, which is indicative of significant emissions of mercury vapor resulting from obsolete equipment and production technologies. No significant non-carcinogenic risk was found for the general residents in the sampling area over the study period, while the risk for the workers in the fluorescent lamp manufacturing facilities and workshops could be higher. These findings indicate that fluorescent lamp manufacturing in the developing countries is a major source of atmospheric mercury.

Unveiling Intrinsic Potassium Storage Behaviors of Hierarchical Nano Bi@N-Doped Carbon Nanocages Framework via In Situ Characterizations.

Metallic bismuth has drawn attention as a promising alloying anode for advanced potassium ion batteries (PIBs). However, serious volume expansion/electrode pulverization and sluggish kinetics always lead to its inferior cycling and rate properties for practical applications. Therefore, advanced Bi-based anodes via structural/compositional optimization and sur-/interface design are needed. Herein, we develop a bottom-up avenue to fabricate nanoscale Bi encapsulated in a 3D N-doped carbon nanocages (Bi@N-CNCs) framework with a void space by using a novel Bi-based metal-organic framework as the precursor. With elaborate regulation in annealing temperatures, the optimized Bi@N-CNCs electrode exhibits large reversible capacities and long-duration cyclic stability at high rates when evaluated as competitive anodes for PIBs. Insights into the intrinsic K+ -storage processes of the Bi@N-CNCs anode are put forward from comprehensive in situ characterizations.

TRAF4 acts as a fate checkpoint to regulate the adipogenic differentiation of MSCs by activating PKM2.

BACKGROUND: Mesenchymal stem cells (MSCs) selectively differentiate into adipocytes or osteoblasts, and several molecules control the fate determination of MSCs. Understanding these key checkpoints greatly contributes to the ability to induce specific MSC differentiation for clinical applications. In this study, we aimed to explore whether TNF receptor-associated factor 4 (TRAF4) affects MSC adipogenic differentiation, which we previously reported that could positively regulated the osteogenic differentiation. METHODS: Western blotting and Real-time Polymerase Chain Reaction were used to detected the expression pattern of TRAF4 during adipogenic differentiation. Lentivirus was constructed to regulate TRAF4 expression, and oil red O staining and Western blotting were used to assess its role in adipogenesis, which was confirmed in vivo by implanting an MSC-matrigel mixture into nude mice. Western blotting was used to detect the activated signaling pathways, and a specific inhibitor and agonist were used to clear the roles of the key signaling pathways. Additionaly, Co-Immunoprecipitation was conducted to find that Pyruvate kinase isozyme type M2 (PKM2) interacts with TRAF4, and to further explore their binding and functional domains. Finally, an RNA-binding protein immunoprecipitation assay and Western blotting were used to detect whether N6-methyladenosine mediates the decreased TRAF4 expression during adipogenic differentiation. FINDINGS: The results demonstrated that TRAF4 negatively regulates MSC adipogenesis in vitro and in vivo. Mechanistically, we revealed that TRAF4 binds to PKM2 to activate the kinase activity of PKM2, which subsequently activates ß-catenin signaling and then inhibits adipogenesis. Furthermore, TRAF4 downregulation during adipogenesis is regulated by ALKBH5-mediated N6-methyladenosine RNA demethylation. INTERPRETATION: TRAF4 negatively regulates the adipogenesis of MSCs by activating PKM2 kinase activity, which may act as a checkpoint to fine-tune the balance of adipo-osteogenic differentiation, and suggests that TRAF4 may be a novel target of MSCs in clinical use and may also illuminate the underlying mechanisms of bone metabolic diseases. FUNDING: This study was supported by the National Natural Science Foundation of China (81871750 and 81971518) and the Science and Technology Project of Guangdong Province (2019B02023600 and 2017A020215070).

Public health risk of toxic metal(loid) pollution to the population living near an abandoned small-scale polymetallic mine.

Small-scale mining activities in many developing countries have caused severe environmental issues to the surrounding areas, which ultimately threatened the health of local populations. Based on detailed characterization of the local drinking water and surface soil, as well as foodstuffs, this study comprehensively assessed the public health risk of toxic metal(loid)s to the population living in three villages surrounding an abandoned small-scale polymetallic mine in southern China. The agricultural soils contained elevated levels of Cu, Zn, As, Cd, and Pb, which originated from the mining district, and as expected, the locally cultivated rice and vegetables were contaminated by As, Cd, and Pb to varying extents. Arsenic occurred in both inorganic and organic forms in the rice and vegetables, with inorganic As (i-As) accounting for 82.2% (45.4-100%) and 94.7% (65.2-100%) of the total As contents in rice and vegetables, respectively. Results of health risk assessment indicate that the residents in the impacted villages had serious non-carcinogenic and carcinogenic risk. Dietary exposure to i-As and Cd through rice and vegetable consumption was the primary cause of non-carcinogenic risk, while i-As intake was the dominant contributor of carcinogenic risk. These findings suggest that significant environmental pollution by toxic metal(loid)s could result from small-scale metal mines, even after being abandoned, and the accumulation of the toxic metal(loid)s in food crops could pose significant health risk to the local residents. Immediate actions should be taken to discourage them from consuming the locally produced food crops, while long-term control measures for containment of toxic metal(loid) pollution are being developed, and high priority should be given to the remediation of Cd and As in the contaminated soils.

Quantitative source apportionment of heavy metal(loid)s in the agricultural soils of an industrializing region and associated model uncertainty.

Heavy metal(loid)s are natural constituents of the Earth's crust, and apportionment of their sources in surface soils is a challenging task. This study evaluated the application of positive matrix factorization (PMF) model, assisted with regression modeling and geospatial mapping, in the quantitative source apportionment of heavy metal(loid)s in the agricultural soils of Handan, a region covering >12,000 km2. Obvious enrichment of As, Cd, Cu, Pb, and Zn was found in the surface soils, with Cd alone accounted for 73 % of the overall potential ecological risk. PMF model revealed that Cd (56.9 %) and Pb (47.8 %) in the region's agricultural soils were predominantly contributed by industrial sources, Fe (71.8 %), Cr (60.0 %), V (52.9 %), Cu (50.7 %), Ni (42.2 %), and Mn (41.4 %) were primarily of lithogenic origin, while Co (54.1 %), As (42.9 %), and Zn (40.0 %) mainly came from the mixed sources of natural background, agricultural sources, and vehicle emissions. Uncertainty analysis showed that the contributions of pollution sources to the soil heavy metal(loid)s estimated by PMF model had considerable variations. While quantitative source apportionment of heavy metal(loid)s in soils could be achieved with PMF based on their spatial distributions, combination with emission inventory and reactive transport are probably necessary to obtain more accurate results.

Construction of a multi-dimensional flexible MnS based paper electrode with ultra-stable and high-rate capability towards efficient sodium storage.

Recently, there has been an urgent need for flexible and low cost rechargeable batteries for the emerging flexible and wearable electronic devices. Herein, MnS nanoparticles embedded in carbon nanowires/reduced graphene oxide (MnS@CNWs/rGO) composite paper were synthesized via a simple yet scalable strategy with Mn based coordination nanowires and graphene oxide as precursors. The combination of multi-dimensional subunits offers not only a robust structure but also abundant pathways for fast electron/ion diffusion. When directly used as a free-standing electrode for sodium ion batteries (SIBs), the ultra-flexible paper anode exhibits excellent mechanical and electrochemical performance, benefitting from the synergistic effects between nano-dimensional MnS encapsulated in CNWs and conductive rGO nanosheets. Remarkably, a high reversible gravimetric/volumetric capacity of ∼560 mA h g-1/∼362.3 mA h cm-3 is obtained using the self-supported flexible electrode at a current density of 0.1 A g-1, which is almost 92.4% of the theoretical capacity of MnS. More competitively, the flexible MnS@CNWs/rGO anode exhibits an unprecedented long cycle life with a high reversible capacity of ∼150 mA h g-1 at 1 A g-1 after 10, 000 cycles. This highly favours the promising application of MnS@CNWs/rGO paper in advanced flexible SIBs as an appealing anode.

Construction of Hierarchical Nanotubes Assembled from Ultrathin V3 S4 @C Nanosheets towards Alkali-Ion Batteries with Ion-Dependent Electrochemical Mechanisms.

Ultrathin core-shell V3 S4 @C nanosheets assembled into hierarchical nanotubes (V3 S4 @C NS-HNTs) are synthesized by a self-template strategy and evaluated as general anodes for alkali-ion batteries. Structural/physicochemical characterizations and DFT calculations bring insights into the intrinsic relationship between crystal structures and electrochemical mechanisms of the V3 S4 @C NS-HNTs electrode. The V3 S4 @C NS-HNTs are endowed with strong structural rigidness owing to the layered VS2 subunits and interlayer occupied V atoms, and efficient alkali-ion adsorption/diffusion thanks to the electroactive V3 S4 -C interfaces. The resulting V3 S4 @C NS-HNTs anode exhibit distinct alkali-ion-dependent charge storage mechanisms and exceptional long-durability cyclic performance in storage of K+ , benefiting from synergistic contributions of pseudocapacitive and reversible intercalation/de-intercalation behaviors superior to those of the conversion-reaction-based Li+ -/Na+ -storage counterparts.

Leaching of heavy metals from abandoned mine tailings brought by precipitation and the associated environmental impact.

Abandoned tailings are one of the most important sources of heavy metal pollution in the areas surrounding mining districts, and significant leaching of heavy metals could be brought by precipitation. This study investigated the leaching of heavy metals from the tailings of a small-scale abandoned polymetallic mine in south China by rainwater with batch and column tests and evaluated the associated environmental impact. The mean contents of Cr, Ni, Cu, Zn, As, Cd, and Pb in the un-weathered mine tailings were 1.46×102, 3.11×102, 4.10×103, 2.18×104, 2.82×102, 5.65×102, and 8.74×103mg/kg, respectively, and appreciable fractions of Cd, Zn, Cu, and Cr in the tailings were present in the acid soluble form. Batch and column leaching tests consistently showed that significant quantities of heavy metals could be released from the mine tailings. Based on the results of column leaching tests, it was estimated that the average fluxes of Cr, Ni, Cu, Zn, As, Cd, and Pb from the mine tailings at the studied mining district leached by precipitation were 3.20, 38.3, 12.5, 1.52×104, 104, 1.08, and 9.26g/ha/yr, respectively. The metal-rich tailing leachate would impact the quality of surface water and soils downhill of the mining district, and pose significant potential ecological risk to the farmland soils, which are irrigated by local surface water. These findings indicate the importance of tailings as a source of heavy metals in the mining districts of south China with heavy precipitation, as well as the need for mitigating the releases of heavy metals and the associated environmental impact from abandoned mine tailings.

Heavy metal pollution caused by small-scale metal ore mining activities: A case study from a polymetallic mine in South China.

Although metal ore mining activities are well known as an important source of heavy metals, soil pollution caused by small-scale mining activities has long been overlooked. This study investigated the pollution of surface soils in an area surrounding a recently abandoned small-scale polymetallic mining district in Guangdong province of south China. A total of 13 tailing samples, 145 surface soil samples, and 29 water samples were collected, and the concentrations of major heavy metals, including Cr, Mn, Co, Ni, Cu, Zn, As, Cd, Pb, and Se, were determined. The results show that the tailings contained high levels of heavy metals, with Cu, Zn, As, Cd, and Pb occurring in the ranges of 739-4.15 × 103, 1.81 × 103-5.00 × 103, 118-1.26 × 103, 8.14-57.7, and 1.23 × 103-6.99 × 103 mg/kg, respectively. Heavy metals also occurred at high concentrations in the mine drainages (15.4-17.9 mg/L for Cu, 21.1-29.3 mg/L for Zn, 0.553-0.770 mg/L for Cd, and 1.17-2.57 mg/L for Pb), particularly those with pH below 3. The mean contents of Cu, Zn, As, Cd, and Pb in the surface soils of local farmlands were up to 7 times higher than the corresponding background values, and results of multivariate statistical analysis clearly indicate that Cu, Zn, Cd, and Pb were largely contributed by the mining activities. The surface soils from farmlands surrounding the mining district were moderately to seriously polluted, while the potential ecological risk of heavy metal pollution was extremely high. It was estimated that the input fluxes from the mining district to the surrounding farmlands were approximately 17.1, 59.2, 0.311, and 93.8 kg/ha/yr for Cu, Zn, Cd, and Pb, respectively, which probably occurred through transport of fine tailings by wind and runoff, and mine drainage as well. These findings indicate the significant need for proper containment of the mine tailings at small-scale metal ore mines.

Comparison of soil heavy metal pollution caused by e-waste recycling activities and traditional industrial operations.

The traditional industrial operations are well recognized as an important source of heavy metal pollution, while that caused by the e-waste recycling activities, which have sprouted in some developing countries, is often overlooked. This study was carried out to compare the status of soil heavy metal pollution caused by the traditional industrial operations and the e-waste recycling activities in the Pearl River Delta, and assess whether greater attention should be paid to control the pollution arising from e-waste recycling activities. Both the total contents and the chemical fractionation of major heavy metals (As, Cr, Cd, Ni, Pb, Cu, and Zn) in 50 surface soil samples collected from the e-waste recycling areas and 20 soil samples from the traditional industrial zones were determined. The results show that the soils in the e-waste recycling areas were mainly polluted by Cu, Zn, As, and Cd, while Cu, Zn, As, Cd, and Pb were the major heavy metals in the soils from the traditional industrial zones. Statistical analyses consistently show that Cu, Cd, Pb, and Zn in the surface soils from both types of sites were contributed mostly by human activities, while As, Cr, and Ni in the soils were dominated by natural background. No clear distinction was found on the pollution characteristic of heavy metals in the surface soils between the e-waste recycling areas and traditional industrial zones. The potential ecological risk posed by heavy metals in the surface soils from both types of sites, which was dominated by that from Cd, ranged from low to moderate. Given the much shorter development history of e-waste recycling and its largely unregulated nature, significant efforts should be made to crack down on illegal e-waste recycling and strengthen pollution control for related activities.

Monocular precrash vehicle detection: features and classifiers.

Robust and reliable vehicle detection from images acquired by a moving vehicle (i.e., on-road vehicle detection) is an important problem with applications to driver assistance systems and autonomous, self-guided vehicles. The focus of this work is on the issues of feature extraction and classification for rear-view vehicle detection. Specifically, by treating the problem of vehicle detection as a two-class classification problem, we have investigated several different feature extraction methods such as principal component analysis, wavelets, and Gabor filters. To evaluate the extracted features, we have experimented with two popular classifiers, neural networks and support vector machines (SVMs). Based on our evaluation results, we have developed an on-board real-time monocular vehicle detection system that is capable of acquiring grey-scale images, using Ford's proprietary low-light camera, achieving an average detection rate of 10 Hz. Our vehicle detection algorithm consists of two main steps: a multiscale driven hypothesis generation step and an appearance-based hypothesis verification step. During the hypothesis generation step, image locations where vehicles might be present are extracted. This step uses multiscale techniques not only to speed up detection, but also to improve system robustness. The appearance-based hypothesis verification step verifies the hypotheses using Gabor features and SVMs. The system has been tested in Ford's concept vehicle under different traffic conditions (e.g., structured highway, complex urban streets, and varying weather conditions), illustrating good performance.

On-road vehicle detection: a review.

Developing on-board automotive driver assistance systems aiming to alert drivers about driving environments, and possible collision with other vehicles has attracted a lot of attention lately. In these systems, robust and reliable vehicle detection is a critical step. This paper presents a review of recent vision-based on-road vehicle detection systems. Our focus is on systems where the camera is mounted on the vehicle rather than being fixed such as in traffic/driveway monitoring systems. First, we discuss the problem of on-road vehicle detection using optical sensors followed by a brief review of intelligent vehicle research worldwide. Then, we discuss active and passive sensors to set the stage for vision-based vehicle detection. Methods aiming to quickly hypothesize the location of vehicles in an image as well as to verify the hypothesized locations are reviewed next. Integrating detection with tracking is also reviewed to illustrate the benefits of exploiting temporal continuity for vehicle detection. Finally, we present a critical overview of the methods discussed, we assess their potential for future deployment, and we present directions for future research.