Congener Variation of Genetic Dependent-Developmental Toxicology in Two Emerging Classes of Dioxin-like Compounds.

Emerging classes of dioxin-like compounds (DLCs) like hydroxylated/methoxylated polybrominated diphenyl ethers (HO-/MeO-PBDEs) and polychlorinated diphenyl sulfides (PCDPSs) could lead to diverse adverse outcomes in humans and wildlife, yet knowledge gaps exist in their molecular mechanisms associated with different structures following early life environmental exposure. This study integrated a genetic knockout technique and concentration-dependent reduced zebrafish transcriptome approach (CRZT) to unravel the toxicological pathways underpinning developmental toxicity of four HO-/MeO-PBDEs and five PCDPSs at environmentally relevant doses. Generally, the dependence of aryl hydrocarbon receptor (AhR) on the embryotoxicity and transcriptomic potencies induced by the HO-PBDEs and PCDPSs varied across different congeners. The knockout of the ahr2 gene led to 1.02- to 76.48-fold decreases of DLC-induced embryotoxicities and reduced the transcriptome-based potencies ranging from 1.38 to 2124.74 folds in the CRZT test. The fold changes denoting AhR-mediated potentials significantly increased with the increasing chlorination degrees of MeO-PBDEs and PCDPSs (p < 0.05). Moreover, ahr2 knockout primarily affected the DLC-induced early molecular responses relevant to DNA damage, enzyme activation, and organ development. Our integrated approach revealed the differential role of AhR in mediating the developmental toxicity of emerging DLCs possessing varied structures at environmentally relevant doses.

Categorization of collagen type I and II blend hydrogel using multipolarization SHG imaging with ResNet regression.

Previously, the discrimination of collagen types I and II was successfully achieved using peptide pitch angle and anisotropic parameter methods. However, these methods require fitting polarization second harmonic generation (SHG) pixel-wise information into generic mathematical models, revealing inconsistencies in categorizing collagen type I and II blend hydrogels. In this study, a ResNet approach based on multipolarization SHG imaging is proposed for the categorization and regression of collagen type I and II blend hydrogels at 0%, 25%, 50%, 75%, and 100% type II, without the need for prior time-consuming model fitting. A ResNet model, pretrained on 18 progressive polarization SHG images at 10° intervals for each percentage, categorizes the five blended collagen hydrogels with a mean absolute error (MAE) of 0.021, while the model pretrained on nonpolarization images exhibited 0.083 MAE. Moreover, the pretrained models can also generally regress the blend hydrogels at 20%, 40%, 60%, and 80% type II. In conclusion, the multipolarization SHG image-based ResNet analysis demonstrates the potential for an automated approach using deep learning to extract valuable information from the collagen matrix.

Genotoxicity Assessment of Haloacetaldehyde Disinfection Byproducts via a Simplified Yeast-Based Toxicogenomics Assay.

Haloacetaldehydes (HALs) represent the third-largest category of disinfection byproducts (DBPs) in drinking water in terms of weight. As a subset of unregulated DBPs, only a few HALs have undergone assessment, yielding limited information regarding their genotoxicity mechanisms. Herein, we developed a simplified yeast-based toxicogenomics assay to evaluate the genotoxicity of five specific HALs. This assay recorded the protein expression profiles of eight Saccharomyces cerevisiae strains fused with green fluorescent protein, including all known DNA damage and repair pathways. High-resolution real-time pathway activation data and protein expression profiles in conjunction with clustering analysis revealed that the five HALs induced various DNA damage and repair pathways. Among these, chloroacetaldehyde and trichloroacetaldehyde were found to be positively associated with genotoxicity, while dichloroacetaldehyde, bromoacetaldehyde, and tribromoacetaldehyde displayed negative associations. The protein effect level index, which are molecular end points derived from a toxicogenomics assay, exhibited a statistically significant positive correlation with the results of traditional genotoxicity assays, such as the comet assay (rp = 0.830 and p < 0.001) and SOS/umu assay (rp = 0.786 and p = 0.004). This yeast-based toxicogenomics assay, which employs a minimal set of gene biomarkers, can be used for mechanistic genotoxicity screening and assessment of HALs and other chemical compounds. These results contribute to bridging the knowledge gap regarding the molecular mechanisms underlying the genotoxicity of HALs and enable the categorization of HALs based on their distinct DNA damage and repair mechanisms.

Exosomes Derived from Hypoxia-Cultured Human Adipose Stem Cells Alleviate Articular Chondrocyte Inflammaging and Post-Traumatic Osteoarthritis Progression.

Osteoarthritis (OA) is the most common age-related degenerative joint disease. Inflammaging, linking inflammation and aging, is found in senescent cells with the secretions of matrix-degrading proteins and proinflammatory cytokines. The senescence-associated secretory phenotype (SASP) plays a very important role in OA progression. However, there remains no effective way to suppress OA progression, especially by suppressing inflammaging and/or the chondrocyte SASP. Recent studies have shown that exosomes derived from hypoxia-cultured BMSCs can regenerate cartilage in OA animal models. Some reports have further indicated that exosomes secreted from MSCs contribute to the efficacy of MSC therapy in OA. However, whether hypoxia-cultured ADSC-secreted exosomes (hypoxia-ADSC-Exos) can alleviate the chondrocyte SASP or OA progression remains unclear. Accordingly, we hypothesized that hypoxia-ADSC-Exos have a beneficial effect on the normal functions of human articular chondrocytes (HACs), can attenuate the SASP of OA-like HACs in vitro, and further suppress OA progression in rats. Hypoxia-ADSC-Exos were derived from ADSCs cultured in 1% O2 and 10% de-Exo-FBS for 48 h. The molecular and cell biological effects of hypoxia-ADSC-Exos were tested on IL1-ß-induced HACs as OA-like HACs in vitro, and the efficacy of OA treatment was tested in ACLT-induced OA rats. The results showed that hypoxia-ADSC-Exos had the best effect on GAG formation in normal HACs rather than those cultured in normoxia or hypoxia plus 2% de-Exo-FBS. We further found that hypoxia-ADSC-Exos alleviated the harmful effect in OA-like HACs by decreasing markers of normal cartilage (GAG and type II collagen) and increasing markers of fibrous or degenerative cartilage (type I or X collagen), matrix degradation enzymes (MMP13 and ADAMT5), and inflammatory cytokines (TNFα and IL-6). More importantly, intra-articular treatment with hypoxia-ADSC-Exos suppressed OA progression, as evidenced by the weight-bearing function test and cartilage GAG quantification in ACLT rats. Moreover, through NGS and bioinformatic analysis, seven potential miRNAs were found in hypoxia-ADSC-Exos, which may contribute to regulating cellular oxidative stress and attenuating cell senescence. In summary, we demonstrated that hypoxia-ADSC-Exos, carrying potent miRNAs, not only improve normal HAC function but also alleviate HAC inflammaging and OA progression. The results suggest that hypoxia-ADSC-Exo treatment may offer another strategy for future OA therapy.

Prediction of zebrafish embryonic developmental toxicity by integrating omics with adverse outcome pathway.

New approach methodologies (NAMs), especially omics-based high-throughput bioassays have been developed rapidly, providing rich mechanistic information such as molecular initiation events (MIEs) and (sub)cellular key events (KEs) in adverse outcome pathways (AOPs). However, how to apply the knowledge of MIEs/KEs to predict adverse outcomes (AOs) induced by chemicals represents a new challenge for computational toxicology. Here, an integrated method named ScoreAOP was developed and evaluated to predict chemicals' developmental toxicity for zebrafish embryos by integrating four related AOPs and dose-dependent reduced zebrafish transcriptome (RZT). The rules of ScoreAOP included 1) sensitivity of responsive KEs demonstrated by point of departure of KEs (PODKE), 2) evidence reliability and 3) distance between KEs and AOs. Moreover, eleven chemicals with different modes of action (MoAs) were tested to evaluate ScoreAOP. Results showed that eight of the eleven chemicals caused developmental toxicity at tested concentration in apical tests. All the tested chemicals' developmental defects were predicted using ScoreAOP, whereas eight out of the eleven chemicals predicted by ScoreMIE which was developed to score MIEs disturbed by chemicals based on in vitro bioassays data. Finally, in terms of mechanism explanation, ScoreAOP clustered chemicals with different MoAs while ScoreMIE failed, and ScoreAOP revealed the activation of aryl hydrocarbon receptor (AhR) plays a significant role in dysfunction of cardiovascular system, resulting in zebrafish developmental defects and mortality. In conclusion, ScoreAOP represents a promising approach to apply mechanism information obtained from omics to predict AOs induced by chemicals.

Polyvinyl Butyral Polymeric Host Material-Based Fluorescent Thin Films to Achieve Highly Efficient Red and Green Colour Conversion for Advanced Next-Generation Displays.

Rare-earth element-free fluorescent materials are eco-friendlier than other traditional fluorescent precursors, such as quantum dots and phosphors. In this study, we explore a simple and facile solution-based technique to prepare fluorescent films, which are highly stable under ordinary room conditions and show hydrophobic behaviour. The proposed hybrid material was designed with hybrid composites that use polyvinyl butyral (PVB) as a host doped with organic dyes. The red and green fluorescent films exhibited quantum yields of 89% and 80%, respectively, and both are very uniform in thickness and water resistant. Additionally, PVB was further compared with another polymeric host, such as polyvinylpyrrolidone (PVP), to evaluate their binding ability and encapsulation behaviour. Next, the effect of PVB on the optical and chemical properties of the fluorescent materials was studied using UV spectroscopy and Fourier transform infrared spectroscopy. The analysis revealed that no new bond was formed between the host material and fluorescent precursor during the process, with intermolecular forces being present between different molecules. Moreover, the thickness of the fluorescent film and quantum yield relation were evaluated. Finally, the hydrophobic nature, strong binding ability, and optical enhancement by PVB provide a powerful tool for fabricating a highly efficient fluorescent film with enhanced stability in an external environment based on its promising encapsulation properties. These efficient fluorescent films have a bright potential in colour conversion for next-generation display applications.

Bioaccumulation, Trophic Transfer, and Biotransformation of Polychlorinated Diphenyl Ethers in a Simulated Aquatic Food Chain.

Polychlorinated diphenyl ethers (PCDEs) are detected in aquatic environments and demonstrate adverse effects in aquatic organisms. However, data regarding the environmental behavior of PCDEs in aquatic ecosystems are lacking. In the present study, a simulated aquatic food chain (Scenedesmus obliquus-Daphnia magna-Danio rerio) was constructed in a lab setting, and the bioaccumulation, trophic transfer, and biotransformation of 12 PCDE congeners were quantitatively investigated for the first time. The log-transformed bioaccumulation factors (BCFs) of PCDEs in S. obliquus, D. magna, and D. rerio were in the range of 2.94-3.77, 3.29-4.03, and 2.42-2.89 L/kg w.w., respectively, indicating the species-specific bioaccumulation of PCDE congeners. The BCF values increased significantly with the increasing number of substituted Cl atoms, with the exception of CDE 209. The number of Cl atoms at the para and meta positions were found to be the major positive contributing factors for BCFs in the case of the same number of substituted Cl. The lipid-normalized biomagnification factors (BMFs) of S. obliquus to D. magna, D. magna to D. rerio, and the whole food chain for the 12 PCDE congeners ranged at 1.08-2.27, 0.81-1.64, and 0.88-3.64, respectively, suggesting that some congeners had BMFs comparable to PBDEs and PCBs. Dechlorination was the only metabolic pathway observed for S. obliquus and D. magna. For D. rerio, dechlorination, methoxylation, and hydroxylation metabolic pathways were observed. 1H nuclear magnetic resonance (NMR) experiments and theoretical calculations confirmed that methoxylation and hydroxylation occurred at the ortho position of the benzene rings. In addition, reliable quantitative structure-property relationship (QSPR) models were constructed to qualitatively describe the relationships between molecular structure descriptors and BCFs for PCDEs. These findings provide insights into the movement and transformation of PCDEs in aquatic ecosystems.

Effects of organic substrates on sulfate-reducing microcosms treating acid mine drainage: Performance dynamics and microbial community comparison.

Bioremediation techniques utilizing sulfate-reducing bacteria (SRB) for acid mine drainage (AMD) treatment have attracted growing attention in recent years, yet substrate bioavailability for SRB is a key factor influencing treatment effectiveness and long-term stability. This study investigated the effects of external organic substrates, including four complex organic wastes (i.e., sugarcane bagasse, straw compost, shrimp shell (SS), and crab shell (CS)) and a small-molecule organic acid (i.e., propionate), on AMD removal performance and associated microbial communities during the 30-day operation of sulfate-reducing microcosms. The results showed that the pH values increased in all five microcosms, while CS exhibited the highest neutralization ability and a maximum alkalinity generation of 1507 mg/L (as CaCO3). Sulfate reduction was more effective in SS and CS microcosms, with sulfate removal efficiencies of 95.6% and 86.0%, respectively. All sulfate-reducing microcosms could remove heavy metals to different degrees, with the highest removal rate of >99.0% observed for aluminum. The removal efficiency of manganese, the most recalcitrant metal, was the highest (96%) in the CS microcosm. Correspondingly, SRB was more abundant in the CS and SS microcosms as revealed by sequencing analysis, while Desulfotomaculum was the dominant SRB in the CS microcosm, accounting for 10.8% of total effective bacterial sequences. Higher abundances of functional genes involved in fermentation and sulfur cycle were identified in CS and SS microcosms. This study suggests that complex organic wastes such as CS and SS could create and maintain preferable micro-environments for active growth and metabolism of functional microorganisms, thus offering a cost-efficient, stable, and environmental-friendly solution for AMD treatment and management.

Characterization of collagen response to bone fracture healing using polarization-SHG.

In this study, we extend on the three parameter analysis approach of utilizing a noninvasive dual-liquid-crystal-based polarization-resolved second harmonic generation (SHG) microscopy to facilitate the quantitative characterization of collagen types I and II in fracture healing tissues. The SHG images under various linear and circular polarization states are analyzed and quantified in terms of the peptide pitch angle (PA), SHG-circular dichroism (CD), and anisotropy parameter (AP). The results show that the collagen PA has a value of 49.26° after 2 weeks of fracture healing (collagen type II domination) and 49.05° after 4 weeks (collagen type I domination). Moreover, the SHG-CD and AP values of the different collagen types differ by 0.05. The change tendencies of the extracted PA, SHG-CD, and AP parameters over the healing time are consistent with the collagen properties of healthy nonfractured bone. Thus, the feasibility of the proposed dual-liquid-crystal-based polarization-SHG method for differentiating between collagen types I and II in bone fracture healing tissue is confirmed.

Ablation of Discoidin Domain Receptor 1 Provokes an Osteopenic Phenotype by Regulating Osteoblast/Osteocyte Autophagy and Apoptosis.

Discoidin domain receptor 1 (DDR1) is a collagen receptor that belongs to the receptor tyrosine kinase family. We have previously shown that DDR1 plays a crucial role during bone development, resulting in dwarfism and a short stature in osteoblast-specific knockout mice (OKO mice). However, the detailed pathophysiological effects of DDR1 on bone development throughout adulthood have remained unclear. This study aims to identify how DDR1 regulates osteoblast and osteocyte functions in vivo and in vitro during bone development in adulthood. The metabolic changes in bone tissues were analyzed using Micro-CT and immunohistochemistry staining (IHC) in vivo; the role of DDR1 in regulating osteoblasts was examined in MC3T3-E1 cells in vitro. The Micro-CT analysis results demonstrated that OKO mice showed a 10% reduction in bone-related parameters from 10 to 14 weeks old and a significant reduction in cortical thickness and diameter compared with flox/flox control mice (FF) mice. These results indicated that DDR1 knockout in OKO mice exhibiting significant bone loss provokes an osteopenic phenotype. The IHC staining revealed a significant decrease in osteogenesis-related genes, including RUNX2, osteocalcin, and osterix. We noted that DDR1 knockout significantly induced osteoblast/osteocyte apoptosis and markedly decreased autophagy activity in vivo. Additionally, the results of the gain- and loss-of-function of the DDR1 assay in MC3T3-E1 cells indicated that DDR1 can regulate the osteoblast differentiation through activating autophagy by regulating the phosphorylation of the mechanistic target of rapamycin (p-mTOR), light chain 3 (LC3), and beclin-1. In conclusion, our study highlights that the ablation of DDR1 results in cancellous bone loss by regulating osteoblast/osteocyte autophagy. These results suggest that DDR1 can act as a potential therapeutic target for managing cancellous bone loss.

Accumulation of high-molecular-weight polycyclic aromatic hydrocarbon impacted the performance and microbial ecology of bioretention systems.

Bioretention has been considered as an effective management practice for urban stormwater in the removal of pollutants including polycyclic aromatic hydrocarbons (PAHs). However, the accumulation of high-molecular-weight (HMW) PAHs in bioretention systems and their potential impact on the pollutants removal performance and microbial ecology are still not fully understood. In this study, comparisons of treatment effectiveness, enzyme activity and microbial community in bioretention systems with different types of media amendments were carried out at different spiking levels of pyrene (PYR). The results showed that the removal efficiencies of chemical oxygen demand (COD) and total nitrogen in the bioretention systems were negatively impacted by the PYR levels. The relative activities of soil dehydrogenase and urease were increasingly inhibited by the elevated PYR level, indicating the declining microbial activity regarding organic matter decomposition. The spiking of PYR negatively affected microbial diversity, and distinct time- and influent-dependent changes in microbial communities were observed. The relative abundance of PAH-degrading microorganisms increased in PYR-spiked systems, while the abundance of nitrifiers decreased. The addition of media amendments was beneficial for the enrichment of microorganisms that are more resistant to PYR-related stress, therefore elevating the COD concentration removal rate by ∼50%. This study gives new insight into the multifaceted impacts of HMW PAH accumulation on microbial fingerprinting and enzyme activities, which may provide guidance on better stormwater management practices via bioretention in terms of improved system longevity and performance.

Problematic Mobile Phone Use Increases with the Fear of Missing Out Among College Students: The Effects of Self-Control, Perceived Social Support and Future Orientation.

INTRODUCTION: Mobile phones bring much convenience to college students' lives, but they also cause problems. Few studies have explored the effect of the fear of missing out (FoMO) on problematic mobile phone use among college students. This study tested the mediating effect of self-control in the relationship between FoMO and problematic mobile phone use. It also explored the moderating roles of perceived social support and future orientation in the relationship between these variables. METHODS: A cross-sectional design was used in this study. Materials include the Fear of Missing Out Scale, Perceived Social Support Scale, Self-control Scale (Chinese version), Mobile Phone Addiction Index, and Consideration of Future Consequences Scale. Of 3606 participants, 3189 completed the questionnaire. SPSS 21 was used to analyze the mediation and moderation effects. RESULTS: The results showed that problematic mobile phone use was positively predicted by FoMO. The relationship between FoMO and problematic mobile phone use was partially mediated by self-control. When the scores of perceived social support and future orientation were high, the negative effect of FoMO on problematic mobile phone use was reduced. CONCLUSION: The negative effect of FoMO on problematic mobile phone use through self-control was moderated by perceived social support and future orientation.

Biodegradation performance and diversity of enriched bacterial consortia capable of degrading high-molecular-weight polycyclic aromatic hydrocarbons.

Polycyclic aromatic hydrocarbons (PAHs) are key organic pollutants in the environment that pose threats to the ecosystem and human health. The degradation of high molecular weight (HMW) PAHs by enriched bacterial consortia has been previously studied, while the involved metabolisms and microbial communities are still unclear and warrant further investigations. In this study, five bacterial consortia capable of utilizing different PAHs (naphthalene, anthracene, and pyrene) as the sole carbon and energy sources were enriched from PAH-contaminated soil samples. Among the five consortia, consortium TC exhibited the highest pyrene degradation efficiency (91%) after 19 d of incubation. The degradation efficiency was further enhanced up to 99% by supplementing yeast extract. Besides, consortium TC showed tolerances to high concentrations of pyrene (up to 1000 mg/L) and different heavy metal stresses (including Zn2+, Cd2+, and Pb2+). The dominant genus in consortium TC, GS, and PL showing relatively higher degradation efficiency for anthracene and pyrene was Pseudomonas, whereas consortium PG and GD were predominated by genus Achromobacter and class Enterobacteriaceae, respectively. Consortium TC, as a highly efficient HMW PAH-degrading consortium, could be applied for synergistic biodegradation of HMW PAHs and in situ bioremediation of the sites contaminated with both PAHs and heavy metals.

The relationship between teacher professional identity and burnout amid the pandemic: A moderated mediation model.

Background: Teacher burnout is affected by personal and social factors. COVID-19 has greatly impacted teachers' physical and mental health, which could aggravate teacher burnout. Purpose: Based on the JD-R model, this study aims to investigate the relationship between teacher professional identity (TPI) and job burnout during the COVID-19 pandemic, and examine the moderating roles of perceived organizational support (POS) and psychological resilience (PR) in these relationships among primary and secondary school teachers in China. Methods: A total of 3,147 primary and secondary school teachers participated in this study. Findings: Work engagement played a mediating role in the relationship between professional identity and burnout; when the POS and PR scores were high, the predictive coefficient of TPI on burnout was the largest. Originality: This study tested the mechanism underlying the relationship between TPI and burnout, and explored the protective factors of burnout. Implications: This study supports the applicability of the JD-R model during COVID-19 and provides ideas for teachers to reduce burnout.

Susceptibility identification for seasonal influenza A/H3N2 based on baseline blood transcriptome.

Introduction: Influenza susceptibility difference is a widely existing trait that has great practical significance for the accurate prevention and control of influenza. Methods: Here, we focused on the human susceptibility to the seasonal influenza A/H3N2 of healthy adults at baseline level. Whole blood expression data for influenza A/H3N2 susceptibility from GEO were collected firstly (30 symptomatic and 19 asymptomatic). Then to explore the differences at baseline, a suite of systems biology approaches - the differential expression analysis, co-expression network analysis, and immune cell frequencies analysis were utilized. Results: We found the baseline condition, especially immune condition between symptomatic and asymptomatic, was different. Co-expression module that is positively related to asymptomatic is also related to immune cell type of naïve B cell. Function enrichment analysis showed significantly correlation with "B cell receptor signaling pathway", "immune response-activating cell surface receptor signaling pathway" and so on. Also, modules that are positively related to symptomatic are also correlated to immune cell type of neutrophils, with function enrichment analysis showing significantly correlations with "response to bacterium", "inflammatory response", "cAMP-dependent protein kinase complex" and so on. Responses of symptomatic and asymptomatic hosts after virus exposure show differences on resisting the virus, with more effective frontline defense for asymptomatic hosts. A prediction model was also built based on only baseline transcription information to differentiate symptomatic and asymptomatic population with accuracy of 0.79. Discussion: The results not only improve our understanding of the immune system and influenza susceptibility, but also provide a new direction for precise and targeted prevention and therapy of influenza.

Dependence of Graphene Oxide (GO) Toxicity on Oxidation Level, Elemental Composition, and Size.

The mass production of graphene oxide (GO) unavoidably elevates the chance of human exposure, as well as the possibility of release into the environment with high stability, raising public concern as to its potential toxicological risks and the implications for humans and ecosystems. Therefore, a thorough assessment of GO toxicity, including its potential reliance on key physicochemical factors, which is lacking in the literature, is of high significance and importance. In this study, GO toxicity, and its dependence on oxidation level, elemental composition, and size, were comprehensively assessed. A newly established quantitative toxicogenomic-based toxicity testing approach, combined with conventional phenotypic bioassays, were employed. The toxicogenomic assay utilized a GFP-fused yeast reporter library covering key cellular toxicity pathways. The results reveal that, indeed, the elemental composition and size do exert impacts on GO toxicity, while the oxidation level exhibits no significant effects. The UV-treated GO, with significantly higher carbon-carbon groups and carboxyl groups, showed a higher toxicity level, especially in the protein and chemical stress categories. With the decrease in size, the toxicity level of the sonicated GOs tended to increase. It is proposed that the covering and subsequent internalization of GO sheets might be the main mode of action in yeast cells.

Design, Manufacturing, and Control of a Pneumatic-Driven Passive Robotic Gait Training System for Muscle-Weakness in a Lower Limb.

We designed and manufactured a pneumatic-driven robotic passive gait training system (PRPGTS), providing the functions of body-weight support, postural support, and gait orthosis for patients who suffer from weakened lower limbs. The PRPGTS was designed as a soft-joint gait training rehabilitation system. The soft joints provide passive safety for patients. The PRPGTS features three subsystems: a pneumatic body weight support system, a pneumatic postural support system, and a pneumatic gait orthosis system. The dynamic behavior of these three subsystems are all involved in the PRPGTS, causing an extremely complicated dynamic behavior; therefore, this paper applies five individual interval type-2 fuzzy sliding controllers (IT2FSC) to compensate for the system uncertainties and disturbances in the PRGTS. The IT2FSCs can provide accurate and correct positional trajectories under passive safety protection. The feasibility of weight reduction and gait training with the PRPGTS using the IT2FSCs is demonstrated with a healthy person, and the experimental results show that the PRPGTS is stable and provides a high-trajectory tracking performance.

Advantageous microbial community development and improved performance of pilot-scale field systems treating high-risk acid mine drainage with crab shell.

Microbial communities are crucial to the effectiveness and stability of bioremediation systems treating acid mine drainage (AMD); however, little research has addressed how they correlate to system performance under changing environmental conditions. In this study, 16S rRNA gene sequencing and quantitative PCR (qPCR) were used to characterize microbial communities within different substrate combinations of crab shell (CS) and spent mushroom compost (SMC) and their association with chemical performance in pilot-scale vertical flow ponds (VFPs) treating high risk AMD in central Pennsylvania over 643 days of operation. As compared to a control containing SMC, VFPs containing CS sustained higher alkalinity, higher sulfate-reducing rates, and more thorough metals removal (>90% for Fe and Al, >50% for Mn and Zn). Correspondingly, CS VFPs supported the growth of microorganisms in key functional groups at increasing abundance and diversity over time, especially more diverse sulfate-reducing bacteria. Through changing seasonal and operational conditions over almost two years, the relative abundance of the core phyla shifted in all reactors, but the smallest changes in functional gene copies were observed in VFPs containing CS. These results suggest that the high diversity and stability of microbial communities associated with CS are consistent with effective AMD treatment.

Intra-articular low-dose parathyroid hormone (1-34) improves mobility and articular cartilage quality in a preclinical age-related knee osteoarthritis model.

AIMS: Osteoarthritis (OA) is prevalent among the elderly and incurable. Intra-articular parathyroid hormone (PTH) ameliorated OA in papain-induced and anterior cruciate ligament transection-induced OA models; therefore, we hypothesized that PTH improved OA in a preclinical age-related OA model. METHODS: Guinea pigs aged between six and seven months of age were randomized into control or treatment groups. Three- or four-month-old guinea pigs served as the young control group. The knees were administered 40 µl intra-articular injections of 10 nM PTH or vehicle once a week for three months. Their endurance as determined from time on the treadmill was evaluated before kill. Their tibial plateaus were analyzed using microcalculated tomography (µCT) and histological studies. RESULTS: PTH increased the endurance on the treadmill test, preserved glycosaminoglycans, and reduced Osteoarthritis Research Society International score and chondrocyte apoptosis rate. No difference was observed in the subchondral plate bone density or metaphyseal trabecular bone volume and bone morphogenetic 2 protein staining. CONCLUSION: Subchondral bone is crucial in the initiation and progression of OA. Although previous studies have shown that subcutaneous PTH alleviates knee OA by improving subchondral and metaphyseal bone mass, we demonstrated that intra-articular PTH injections improved spontaneous OA by directly affecting the cartilage rather than the subchondral or metaphyseal bone in a preclinical age-related OA model. Cite this article: Bone Joint Res 2021;10(8):514-525.

SS-31 efficacy in a mouse model of Friedreich ataxia by upregulation of frataxin expression.

Friedreich ataxia (FRDA) is a serious hereditary neurodegenerative disease, mostly accompanied with hypertrophic cardiomyopathy, caused by the reduced expression of frataxin (FXN). However, there is still no effective treatment. Our previous studies have shown that SS-31, a mitochondrion-targeted peptide, is capable to upregulate the expression of FXN and improve the mitochondrial function in cells derived from FRDA patients. To further explore the potential of SS-31, we used the GAA expansion-based models, including Y47 and YG8R (Fxn KIKO) mice, primary neurons and macrophages from the mice and cells derived from FRDA patients. After once-daily intraperitoneal injection of 1 mg/kg SS-31 for 1 month, we observed the significant improvement of motor function. The vacuolation in dorsal root ganglia, lesions in dentate nuclei and the lost thickness of myelin sheath of spinal cord were all repaired after SS-31 treatment. In addition, the hypertrophic cardiomyocytes and disarrayed abnormal Purkinje cells were dramatically reduced. Interestingly, we found that SS-31 treatment upregulated FXN expression not only at the translational levels as observed in cell culture but also at mRNA levels in vivo. Consequently, mitochondrial morphology and function were greatly improved in all tested tissues. Importantly, our data provided additional evidence that the maintenance of the therapeutic benefits needed continuous drug administration. Taken together, our findings have demonstrated the effectiveness of SS-31 treatment through the upregulation of FXN in vivo and offer guidance of the potential usage in the clinical application for FRDA.