Occurrence and spatiotemporal distribution of arsenic biotransformation genes in urban dust.

Microbially-mediated arsenic biotransformation plays a pivotal role in the biogeochemical cycling of arsenic; however, the presence of arsenic biotransformation genes (ABGs) in urban dust remains unclear. To investigate the occurrence and spatiotemporal distributions of ABGs, a total of one hundred and eighteen urban dust samples were collected from different districts of Xiamen city, China in summer and winter. Although inorganic arsenic species, including arsenate [As(V)] and arsenite [As(III)], were found to be predominant, the methylated arsenicals, particularly trimethylarsine oxide [TMAs(V)O] and dimethylarsenate [DMAs(V)], were detected in urban dust. Abundant ABGs were identified in urban dust via AsChip analysis (a high-throughput qPCR chip for ABGs), of which As(III) S-adenosylmethionine methyltransferase genes (arsM), As(V) reductase genes (arsC), As(III) oxidase genes (aioA), As(III) transporter genes (arsB), and arsenic-sensing regulator genes (arsR) were the most prevalent, collectively constituting more than 90 % of ABGs in urban dust. Microbes involved in arsenic methylation were assigned to bacteria (e.g., Actinomycetes and Alphaproteobacteria), archaea (e.g., Halobacteria), and eukaryotes (e.g., Chlamydomonadaceae) in urban dust via the arsM amplicon sequencing. Temperature, a season-dependent environmental factor, profoundly affected the abundance of ABGs and the composition of microbes involved in arsenic methylation. This study provides new insights into the presence of ARGs within the urban dust.

In situ synthesis of layered nickel organophosphonates for efficient aqueous nickel-zinc battery cathodes.

Aqueous nickel-zinc (Ni-Zn) batteries have received increasing research interests because of their reliable safety and economical-friendliness. However, the retarded ionic diffusion, low capacity and limited stability of traditional Ni-based cathodes greatly impedes the practical application of Ni-Zn batteries. Herein, two metal organophosphonate materials of Ni methylphosphonate (Ni-MPA) and Ni phenylphosphonate (Ni-PPA) directly grown on Ni foam are constructed successfully through one step solvothermal technique. These two self-supported Ni organophosphonates featured hybrid two-dimensional (2D) structures consisting of alternating inorganic and organic layers, where the inorganic layers are formed by six-coordinated Ni2+ bridged by oxygen atoms and capped by organophosphonate groups, availing to provide rich open redox reaction sites, rapid ion diffusion and structural flexibility. The research results reveal that the organic groups in phosphonic acid ligands have important influence on their electrochemical properties. Consequently, the Ni-MPA electrode exhibits a higher specific capacity of 2.27 mAh/cm2 compared to that of the Ni-PPA electrode (1.1 mAh/cm2) at 3.0 mA/cm2; however, it demonstrates a more rapid transformation rate into Ni(OH)2 in an alkaline solution. Furthermore, the constructed Ni-MPA//Zn battery can deliver an impressive areal energy density of 2.95 mWh/cm2, good rate performance as well as a long-term cycling stability.

Engineering iron carbide catalyst with aerophilic and electron-rich surface for improved electrochemical CO2 reduction.

Highly efficient electrocatalyst for carbon dioxide reduction (CO2RR) is desirable for converting CO2 into carbon-based chemicals and reducing anthropogenic carbon emission. Regulating catalyst surface to improve the affinity for CO2 and the capability of CO2 activation is the key to high-efficiency CO2RR. In this work, we develop an iron carbide catalyst encapsulated in nitrogenated carbon (SeN-Fe3C) with an aerophilic and electron-rich surface by inducing preferential formation of pyridinic-N species and engineering more negatively charged Fe sites. The SeN-Fe3C exhibits an excellent CO selectivity with a CO Faradaic efficiency (FE) of 92 % at -0.5 V (vs. RHE) and remarkably enhanced CO partial current density as compared to the N-Fe3C catalyst. Our results demonstrate that Se doping reduces the Fe3C particle size and improves the dispersion of Fe3C on nitrogenated carbon. More importantly, the preferential formation of pyridinic-N species induced by Se doping endows the SeN-Fe3C with an aerophilic surface and improves the affinity of the SeN-Fe3C for CO2. Density functional theory (DFT) calculations reveal that the electron-rich surface, which is caused by pyridinic N species and much more negatively charged Fe sites, leads to a high degree of polarization and activation of CO2 molecule, thus conferring a remarkably improved CO2RR activity on the SeN-Fe3C catalyst.

Bioaccessibility of microplastic-associated heavy metals using an in vitro digestion model and its implications for human health risk assessment.

Microplastics can act as carriers of heavy metals and may enter humans through ingestion and threaten human health. However, the bioaccessibility of heavy metals associated with microplastics and its implications for human health risk assessments are poorly understood. Therefore, in this study, four typical heavy metals (As(V), Cr(VI), Cd(II), and Pb(II)) and one typical microplastic (polyvinyl chloride, PVC) were chosen to estimate the human health risk of microplastic-associated heavy metals by incorporating bioaccessibility. Significant adsorption of heavy metals was observed with the following order for adsorption capacity: Pb(II) > Cr(VI) > Cd(II) > As(V); the efficiencies for desorption of these four heavy metals from PVC microplastics were all below 10%. The Fourier transform infrared spectroscopy results indicated that the functional groups on the surface of the virgin PVC microplastics did not play an important role in the capture process. Heavy metals in both gastric and small intestinal phases were prone to release from PVC microplastics when bioaccessibility was evaluated with the in vitro SBRC (Soluble Bioavailability Research Consortium) digestion model. In addition, Pb(II) bioaccessibility in the gastric phase was significantly higher than those in the other phases, while As(V), Cr(VI), and Cd(II) bioaccessibilities showed the opposite trend. After incorporating bioaccessibility adjustments, the noncarcinogenic hazards and carcinogenic risks determined were lower than those based on total metal contents. The individual hazard quotients (HQ) and carcinogenic risks (CR) for ingestion of these four heavy metals from PVC microplastics were all lower than the threshold values for adults and children. In summary, this study will provide a new view of the human health risks of heavy metals associated with microplastics.

CD38 Drives Progress of Osteoarthritis by Affecting Cartilage Homeostasis.

OBJECTIVE: To observe expression of CD38, a key modulator of nicotinamide dinucleotide (NAD+) metabolism in mice with knee osteoarthritis, and protective effect of CD38 inhibition during the osteoarthritis (OA) development. METHOD: The destabilization of the medial meniscus (DMM) model was performed in mice to mimic the process of OA. Immunofluorescence of CD38 was performed to evaluate its response during the OA process. Limb bud-derived mesenchymal cells were isolated for micromass culture. 100 nM or 1 µM CD38 inhibitor (78c) treatment for 14 days and CD38 sgRNA infection were then used to explore the effects of chondrogenic differentiation via Alcian blue staining. The expressions of chondrogenic markers were detected using RT-PCR and Western blot. To explore the protective effect of CD38 inhibitor on cartilage degradation during OA in vivo, a CD38 inhibitor was injected into the knee joint after DMM operations. Micro-CT analysis and Safranin O-fast green staining were used to evaluate subchondral bone micro-architecture changes and cartilage degeneration. RESULTS: Compared to the control group, the CD38 expression in superficial cartilage was obviously increased in DMM group (P < 0.05). During the normal chondrogenic differentiation, the extracellular matrix formed and expression of Sox9, Col2, aggrecan increased apparently while CD38 expression decreased, which could be reversed with ablation of CD38 in limb bud-derived mesenchymal cells. Consistent with findings in vitro, CD38 blockage via CD38 inhibitor injection protected against osteosclerosis in medial subchondral bone and cartilage degeneration in DMM-induced experimental mice. Compared to the Sham group, DMM mice showed significantly increased values of BV and BV/TV in subchondral bone (P < 0.05) and Mankin score, which could be rescued by 78c treatment (P < 0.05). Also the CD38 inhibitor contributed to homeostasis of anabolism and catabolism by upregulating Sox9, Col2, aggrecan and downregulating Runx2, Col10 and Mmp13. CONCLUSION: This study primarily implicates CD38 as an important regulator of chondrogenic differentiation. Inhibition of CD38 demonstrated protection against cartilage degeneration, which suggests that CD38 could be a potential therapeutic target for OA.

Incorporating bioaccessibility and source apportionment into human health risk assessment of heavy metals in urban dust of Xiamen, China.

Heavy metals in urban dust could pose noticeable human health risks, but there are few studies focusing on comprehensive human health risk assessment with the incorporation of both bioaccessibility and source apportionment in urban dust. Thus, fifty-eight urban dust samples were collected from kindergartens in Xiamen to analyze the bioaccessibility-based, source-specific health risk of heavy metals (V, Co, Ni, As, Mo, Cr, Mn, Cu, Zn, and Pb). Most heavy metals, except for V and Mn, were significantly enriched in urban dust based on their values of geoaccumulation index (Igeo) and may be influenced by human activities. The oral bioaccessibility values of heavy metals, which were estimated by the Solubility/Bioaccessibility Research Consortium (SBRC) in vitro model, ranged from 1.563% to 76.51%. The source apportionment determined by applying the absolute principal component analysis-multiple linear regression (APCS-MLR) model indicated five main potential sources, coal combustion, traffic and industrial, natural, construction and furniture sources, and unidentified sources, with contributions of 34.09%, 20.72%, 18.72%, 7.597% and 18.87%, respectively, to the accumulation of heavy metals in urban dust. After incorporating bioaccessibility adjustments, lower non-carcinogenic and carcinogenic risks of heavy metals were observed than those based on total metal content, with the mean hazard index (HI) values being less than the threshold value (1) and the mean total carcinogenic risk (TCR) values exceeding the precautionary criterion (10-6) for both adults and children. By combining bioaccessibility-based health risk assessment and source apportionment, traffic and industrial emissions and coal combustion dominated the noncarcinogenic and carcinogenic risks induced by heavy metals in urban dust, respectively. This study is expected to promote the systematic integration of source apportionment and bioaccessibility into health risk estimation for heavy metal contamination in urban dust, thus providing useful implications for better human health protection.

Inter-rater agreement of rotator cuff tendon and muscle magnetic resonance imaging parameters evaluated preoperatively and during the first postoperative year following rotator cuff repair.

BACKGROUND: Magnetic resonance imaging (MRI) is standard of care for rotator cuff evaluation, with clinical interpretation usually limited to qualitative judgments. The reliability of MRI-based measurements and scoring systems has been evaluated only preoperatively or ≥6 months following rotator cuff repair, when repairs are in the later stages of healing. This study describes the MRI assessments and inter-rater agreement of various rotator cuff tendon and muscle parameters evaluated preoperatively and 4 times during the first postoperative year. METHODS: Two musculoskeletal radiologists independently assessed MRI scans of 42 patients preoperatively and 3, 12, 26, and 52 weeks after rotator cuff repair. Using standardized reading rules, readers assessed tendon integrity (5-point Sugaya classification), tear dimensions, muscle fat (5-point Goutallier classification) and atrophy (4-point Warner classification), muscle cross-sectional areas, and myotendinous junction distance. Raw exact agreement proportions, κ statistics, and correlation coefficients were used to quantify inter-rater agreement. RESULTS: Readers showed moderate to substantial above-chance agreement in scoring rotator cuff tendon integrity and supraspinatus muscle atrophy and good to excellent agreement on tear dimensions and muscle cross-sectional areas but only fair to moderate agreement for fatty infiltration and myotendinous junction distance. Only fatty infiltration grades evidenced observer bias. Inter-rater agreement did not appear time dependent. CONCLUSION: By use of defined reading rules in a research setting, MRI evaluations of rotator cuff tendon integrity, tear dimensions, muscle atrophy, and cross-sectional areas have reasonable reliability at all time points in the first postoperative year. However, the presence of clinically significant disagreements, even in such favorable circumstances, indicates the need for improved imaging tools for precise rotator cuff evaluation.

Inhibition of PTEN activity promotes IB4-positive sensory neuronal axon growth.

Traumatic nerve injuries have become a common clinical problem, and axon regeneration is a critical process in the successful functional recovery of the injured nervous system. In this study, we found that peripheral axotomy reduces PTEN expression in adult sensory neurons; however, it did not alter the expression level of PTEN in IB4-positive sensory neurons. Additionally, our results indicate that the artificial inhibition of PTEN markedly promotes adult sensory axon regeneration, including IB4-positive neuronal axon growth. Thus, our results provide strong evidence that PTEN is a prominent repressor of adult sensory axon regeneration, especially in IB4-positive neurons.

Knocking Out Non-muscle Myosin II in Retinal Ganglion Cells Promotes Long-Distance Optic Nerve Regeneration.

In addition to altered gene expression, pathological cytoskeletal dynamics in the axon are another key intrinsic barrier for axon regeneration in the central nervous system (CNS). Here, we show that knocking out myosin IIA and IIB (myosin IIA/B) in retinal ganglion cells alone, either before or after optic nerve crush, induces significant optic nerve regeneration. Combined Lin28a overexpression and myosin IIA/B knockout lead to an additive promoting effect and long-distance axon regeneration. Immunostaining, RNA sequencing, and western blot analyses reveal that myosin II deletion does not affect known axon regeneration signaling pathways or the expression of regeneration-associated genes. Instead, it abolishes the retraction bulb formation and significantly enhances the axon extension efficiency. The study provides clear evidence that directly targeting neuronal cytoskeleton is sufficient to induce significant CNS axon regeneration and that combining altered gene expression in the soma and modified cytoskeletal dynamics in the axon is a promising approach for long-distance CNS axon regeneration.

c-Myc controls the fate of neural progenitor cells during cerebral cortex development.

The anatomical structure of the mammalian cerebral cortex is the essential foundation for its complex neural activity. This structure is developed by proliferation, differentiation, and migration of neural progenitor cells (NPCs), the fate of which is spatially and temporally regulated by the proper gene. This study was used in utero electroporation and found that the well-known oncogene c-Myc mainly promoted NPCs' proliferation and their transformation into intermediate precursor cells. Furthermore, the obtained results also showed that c-Myc blocked the differentiation of NPCs to postmitotic neurons, and the expression of telomere reverse transcriptase was controlled by c-Myc in the neocortex. These findings indicated c-Myc as a key regulator of the fate of NPCs during the development of the cerebral cortex.

Telomerase Reverse Transcriptase and p53 Regulate Mammalian Peripheral Nervous System and CNS Axon Regeneration Downstream of c-Myc.

Although several genes have been identified to promote axon regeneration in the CNS, our understanding of the molecular mechanisms by which mammalian axon regeneration is regulated is still limited and fragmented. Here by using female mouse sensory axon and optic nerve regeneration as model systems, we reveal an unexpected role of telomerase reverse transcriptase (TERT) in regulation of axon regeneration. We also provide evidence that TERT and p53 act downstream of c-Myc to control sensory axon regeneration. More importantly, overexpression of p53 in sensory neurons and retinal ganglion cells is sufficient to promote sensory axon and optic never regeneration, respectively. The study reveals a novel c-Myc-TERT-p53 signaling pathway, expanding horizons for novel approaches promoting CNS axon regeneration.SIGNIFICANCE STATEMENT Despite significant progress during the past decade, our understanding of the molecular mechanisms by which mammalian CNS axon regeneration is regulated is still fragmented. By using sensory axon and optic nerve regeneration as model systems, the study revealed an unexpected role of telomerase reverse transcriptase (TERT) in regulation of axon regeneration. The results also delineated a c-Myc-TERT-p53 pathway in controlling axon growth. Last, our results demonstrated that p53 alone was sufficient to promote sensory axon and optic nerve regeneration in vivo Collectively, the study not only revealed a new mechanisms underlying mammalian axon regeneration, but also expanded the pool of potential targets that can be manipulated to enhance CNS axon regeneration.

Regulation of adult mammalian intrinsic axonal regeneration by NF-κB/STAT3 signaling cascade.

The inflammatory response is a critical regulator for the regeneration of axon following nervous system injury. Nuclear factor-kappa B (NF-κB) is characteristically known for its ubiquitous role in the inflammatory response. However, its functional role in adult mammalian axon growth remains elusive. Here, we found that the NF-κB signaling pathway is activated in adult sensory neurons through peripheral axotomy. Furthermore, inhibition of NF-κB in peripheral sensory neurons attenuated their axon growth in vitro and in vivo. Our results also showed that NF-κB modulated axon growth by repressing the phosphorylation of STAT3. Furthermore, activation of STAT3 significantly promoted adult optic nerve regeneration. Taken together, the findings of our study indicated that NF-κB/STAT3 cascade is a critical regulator of intrinsic axon growth capability in the adult nervous system.

Influence of technical processing units on polyphenols and antioxidant capacity of carrot (Daucus carrot L.) juice.

The effect of three processing units (blanching, enzyme liquefaction, and pasteurisation) on polyphenols and antioxidant activity of carrot juices was investigated. Polyphenols and antioxidant activity of carrot juices varied with different processes. Five polyphenolic acids were identified in fresh carrot juice, and the predominant compound was chlorogenic acid. Compared with fresh carrot juice, blanching and enzyme liquefaction could result in the increase of the total polyphenol content (TPC) and the antioxidant activity in scavenging DPPH free radicals (DPPH) and Fe(2+)-chelating capacity (FC), whereas pasteurisation could result in the decrease of the TPC and the antioxidant activity in DPPH and FC. Meanwhile blanching, enzyme liquefaction, and pasteurisation showed little influence on the antioxidant activity in lipid peroxidation protection. The antioxidant activities in DPPH and FC increased with increasing concentration while no correlation between lipid peroxidation protection and polyphenols concentration. Polyphenols still retained high antioxidant activity after the processes, which have potential health benefits for consumers.

Morphological and functional characteristics of three-dimensional engineered bone-ligament-bone constructs following implantation.

The incidence of ligament injury has recently been estimated at 400,000/year. The preferred treatment is reconstruction using an allograft, but outcomes are limited by donor availability, biomechanical incompatibility, and immune rejection. The creation of an engineered ligament in vitro solely from patient bone marrow stromal cells (has the potential to greatly enhance outcomes in knee reconstructions. Our laboratory has developed a scaffoldless method to engineer three-dimensional (3D) ligament and bone constructs from rat bone marrow stem cells in vitro. Coculture of these two engineered constructs results in a 3D bone-ligament-bone (BLB) construct with viable entheses, which was successfully used for medial collateral ligament (MCL) replacement in a rat model. 1 month and 2 month implantations were applied to the engineered BLBs. Implantation of 3D BLBs in a MCL replacement application demonstrated that our in vitro engineered tissues grew and remodeled quickly in vivo to an advanced phenotype and partially restored function of the knee. The explanted 3D BLB ligament region stained positively for type I collagen and elastin and was well vascularized after 1 and 2 months in vivo. Tangent moduli of the ligament portion of the 3D BLB 1 month explants increased by a factor of 2.4 over in vitro controls, to a value equivalent to those observed in 14-day-old neonatal rat MCLs. The 3D BLB 1 month explants also exhibited a functionally graded response that closely matched native MCL inhomogeneity, indicating the constructs functionally adapted in vivo.

The effect of implantation on scaffoldless three-dimensional engineered bone constructs.

Our laboratory has previously developed scaffoldless engineered bone constructs (EBC). Bone marrow stromal cells (BMSC) were harvested from rat femur and cultured in medium that induced osteogenic differentiation. After reaching confluence, the monolayer of cells contracted around two constraint points forming a cylinder. EBCs were placed in small diameter (0.5905 x 0.0625 in.) or large diameter (0.5905 x 0.125 in.) silicone tubing and implanted intramuscularly in the hind limb of a rat. Bone mineral content (BMC) of the EBC was analyzed before implantation and at 1 and 2 mo following implantation and compared to that of native femur bone at different stages of development. Negligible BMC was observed in E-20 femur or EBCs prior to implantation. One-month implantation in both small and large tubing increased BMC in the EBC. BMC of EBC from large tubing was greater than in 14 d rat neonatal femurs, but was 2% and 3% of BMC content in adult bone after 1 and 2 mo of implantation, respectively. Alizarine Red and osteopontin staining of the EBCs before and after implantation confirmed increased bone mineralization in the implanted EBCs. Implanted EBCs also had extensive vascularization. Our data suggest that BMSC can be successfully used for the generation of scaffoldless EBC, and this model can be potentially used for the generation of autologous bone transplants in humans.