Structural Reversibility of Nanoscaled Sn Anodes.

Alloying-type anode materials provide high capacity for lithium-ion batteries; however, they suffer pulverization problems resulting from the volume change during cycling. Realizing the cycling reversibility of these anodes is therefore critical for sustaining their electrochemical performance. Here, we investigate the structural reversibility of Sn NPs during cycling at atomic-level resolution utilizing in situ high-resolution TEM. We observed a surprisingly near-perfect structural reversibility after a complete cycle. A three-step phase transition happens during lithiation, accompanied by the generation of a significant number of defects, grain boundaries, and up to 202% volume expansion. In subsequent delithiation, the volume, morphology, and crystallinity of the Sn NPs were restored to their initial state. Theoretical calculations show that compressive stress drives the removal of vacancies generated within the NPs during delithiation, therefore maintaining their intact morphology. This work demonstrates that removing vacancies during cycling can efficiently improve the structural reversibility of high-capacity anode materials.

Downregulation of circ_0035292 Alleviates LPS-Induced WI-38 Cell Injury via Targeting miR-494-3p/TLR4 Pathway in Infantile Pneumonia.

Circular RNAs (circRNAs) have been confirmed to mediate infantile pneumonia development. In this, we investigated the role and new mechanism of circ_0035292 regulating infantile pneumonia progression. Lipopolysaccharide (LPS)-treated WI-38 cells were used to mimic infantile pneumonia cell injury models. Quantitative real-time PCR was used to measure circ_0035292, microRNA (miR)-494-3p and toll-like receptor 4 (TLR4). Cell proliferation and apoptosis were assessed by MTT assay, EdU assay, and flow cytometry. Protein expression was tested using western blot analysis. Inflammation and oxidative stress were evaluated by measuring IL-6, IL-1ß, MDA and SOD levels using ELISA assay and corresponding kits. RNA interaction was confirmed by dual-luciferase reporter assay and RIP assay. Circ_0035292 had elevated expression in infantile pneumonia patients and LPS-induced WI-38 cells. Silenced circ_0035292 could enhance WI-38 cell proliferation, while suppress apoptosis, inflammation and oxidative stress under LPS treatment. Mechanically, circ_0035292 targeted miR-494-3p to positively regulate TLR4. The rescue experiments indicated that miR-494-3p inhibitor abolished the function of circ_0035292 knockdown, and TLR4 overexpression reversed the inhibitory effect of miR-494-3p on LPS-induced WI-38 cell injury. Circ_0035292 might be a potential target for infantile pneumonia treatment, which knockdown could relieve LPS-induced cell injury via the regulation of miR-494-3p/TLR4 axis.

Melatonin Delays Arthritis Inflammation and Reduces Cartilage Matrix Degradation through the SIRT1-Mediated NF-κB/Nrf2/TGF-ß/BMPs Pathway.

Cartilage, a flexible and smooth connective tissue that envelops the surfaces of synovial joints, relies on chondrocytes for extracellular matrix (ECM) production and the maintenance of its structural and functional integrity. Melatonin (MT), renowned for its anti-inflammatory and antioxidant properties, holds the potential to modulate cartilage regeneration and degradation. Therefore, the present study was devoted to elucidating the mechanism of MT on chondrocytes. The in vivo experiment consisted of three groups: Sham (only the skin tissue was incised), Model (using the anterior cruciate ligament transection (ACLT) method), and MT (30 mg/kg), with sample extraction following 12 weeks of administration. Pathological alterations in articular cartilage, synovium, and subchondral bone were evaluated using Safranin O-fast green staining. Immunohistochemistry (ICH) analysis was employed to assess the expression of matrix degradation-related markers. The levels of serum cytokines were quantified via Enzyme-linked immunosorbent assay (ELISA) assays. In in vitro experiments, primary chondrocytes were divided into Control, Model, MT, negative control, and inhibitor groups. Western blotting (WB) and Quantitative RT-PCR (q-PCR) were used to detect Silent information regulator transcript-1 (SIRT1)/Nuclear factor kappa-B (NF-κB)/Nuclear factor erythroid-2-related factor 2 (Nrf2)/Transforming growth factor-beta (TGF-ß)/Bone morphogenetic proteins (BMPs)-related indicators. Immunofluorescence (IF) analysis was employed to examine the status of type II collagen (COL2A1), SIRT1, phosphorylated NF-κB p65 (p-p65), and phosphorylated mothers against decapentaplegic homolog 2 (p-Smad2). In vivo results revealed that the MT group exhibited a relatively smooth cartilage surface, modest chondrocyte loss, mild synovial hyperplasia, and increased subchondral bone thickness. ICH results showed that MT downregulated the expression of components related to matrix degradation. ELISA results showed that MT reduced serum inflammatory cytokine levels. In vitro experiments confirmed that MT upregulated the expression of SIRT1/Nrf2/TGF-ß/BMPs while inhibiting the NF-κB pathway and matrix degradation-related components. The introduction of the SIRT1 inhibitor Selisistat (EX527) reversed the effects of MT. Together, these findings suggest that MT has the potential to ameliorate inflammation, inhibit the release of matrix-degrading enzymes, and improve the cartilage condition. This study provides a new theoretical basis for understanding the role of MT in decelerating cartilage degradation and promoting chondrocyte repair in in vivo and in vitro cultured chondrocytes.

Review on treatment and utilization of barium slag in China.

Barium slag (BS) is generated as a by-product waste during the production of barium salts from barite. A large amount of BS is discharged annually threating the ecological environment and restricting the development of the barium salts industry. In China, BS is classified as hazardous waste due to its corrosivity, and more importantly because of its extraction toxicity of barium. Soluble barium is toxic and can result in barium poisoning for environment and human beings. The current review presents a detailed summary on general characteristics, discharge and disposal status, harmless treatment pathways and comprehensive utilization of BS in China. BaO, SiO2, CaO, and SO3 occur as main chemical compositions in BS, especially BaO accounting approximately for 35-40%. The mineral compositions include unreacted barite, quartz, clay minerals, newly-formed phases from the side reactions such as BaCO3, BaSiO3 and BaSO3, and residual carbon. A special attention is given to the assessment of the harmless treatment methods for BS from hazardous waste to general waste, which will decrease its management costs. Precipitation and solidification of soluble barium is the common pathway for harmless treatment of BS, and the using of other industrial waste can realize cost-saving. Methods for comprehensive utilization of BS include recovery of barium and carbon, application in building materials, and using as adsorbents for wastewater treatment. In particular, we analyzed and discussed the advantages and disadvantages of these existing process routes, intending to promote potentials for comprehensive utilization of BS in the future.

Opening a door to the spatiotemporal history of plants from the tropical Indochina Peninsula to subtropical China.

The complexity of global biodiversity in the tropical Indochina Peninsula and subtropical China bioregions has fascinated biologists for decades, but little is known about the spatiotemporal patterns in these regions. Accordingly, the aims of present study were to investigate the evolutionary and distribution patterns of Engelhardia in these regions and establish a model for examining biogeographic patterns and geological events throughout the tropical Indochina Peninsula and subtropical China. The effects of geological events occurring in the area between the Indochina Peninsula and subtropical China bioregions on the two trees species (i.e., E. roxburghiana and E. fenzelii) were evaluated. A robust phylogenetic framework of 884 individuals from 79 populations was used to generate time-calibrated cytoplasmic and nuclear phylogenetic frameworks based on cpDNA, nrDNA, and nSSR data, respectively. When considered along with ancestral area reconstructions, the genetic data were also used to assess and reconstruct the species' population genetic structure and diversity. These analyses yielded important information about the (1) historical distribution relationships between the tropical and subtropical flora of China; (2) effects of the East Asian summer monsoon (EASM) on the evolutionary history of Asia's plants; and (3) importance of biogeography in conservation planning. Although cytoplasmic-nuclear discordance indicated cpDNA and nrDNA were subject to distinct evolutionary mechanisms that reflected respective evolutionary histories of the plastid and nuclear genomes of prior demographic and biogeographic events. The tropical elements of Engelhardia occupied the Indochina Peninsula during the early Eocene, whereas the subtropical elements were transformed from the tropical elements during Miocene cooling and the onset of the EASM at the Oligocene-Miocene boundary, intensified during the late Miocene and Pliocene, facilitating the transformation of Engelhardia from the tropical Indochina Peninsula to subtropical China. Demographic history provided insights into prominent planning frameworks in conservation biology, namely that subtropical China functioned as a refugium during past climate oscillations and will continue to serve in this capacity in the future.

Drivers of phenotypic variation in cartilage: Circadian clock genes.

Endogenous homeostasis and peripheral tissue metabolism are disrupted by irregular fluctuations in activation, movement, feeding and temperature, which can accelerate negative biological processes and lead to immune reactions, such as rheumatoid arthritis (RA) and osteoarthritis (OA). This review summarizes abnormal phenotypes in articular joint components such as cartilage, bone and the synovium, attributed to the deletion or overexpression of clock genes in cartilage or chondrocytes. Understanding the functional mechanisms of different genes, the differentiation of mouse phenotypes and the prevention of joint ageing and disease will facilitate future research.

Gut microbiota changes in preeclampsia, abnormal placental growth and healthy pregnant women.

BACKGROUND: Preeclampsia (PE) is a condition of high blood pressure that is usually concurrent with proteinuria in pregnancy. PE complicates the management of both maternal and fetal health and contributes to most adverse pregnancy outcomes, but the mechanism underlying the development of PE remains unclear. In this study, we performed a case-control study to compare the gut microbiota of PE (n = 26), abnormal placental growth (APG, n = 25) and healthy pregnant women (n = 28) and analyzed the potential pathogenic role of gut microbiota in PE progression. RESULTS: The clinical pathophysiological state did not affect the bacterial diversity, while the compositions of the gut microbiota were significantly altered in both the PE and APG groups compared with healthy pregnant women. At the phylum level, TM7 was significantly increased in women with APG. Heterogeneity was observed at the genus level, especially in genera with positive LDA scores, suggesting the stage-dependent effect of gut microbiota on the development of PE. The beneficial bacterium Lactobacillus was markedly depleted in the PE and APG groups but was only correlated with blood pressure (BP) and proteinuria levels in the PE group. Two different bacterial taxa belonged to Lactobacillus showed different correlations (OTU255 and OTU784 were significantly related to PE and APG, respectively). CONCLUSIONS: Our results indicated that shifts in the gut microbiota might occur from the early stages of the development of PE, which is of possible etiological and therapeutic importance.

The potential role of senescence in limiting fibrosis caused by aging.

Fibrosis-related diseases carry with them a high mortality rate and their morbidity increases with age. Recent findings indicate that induced senescence in myofibroblasts can limit or reduce myocardial fibrosis, cirrhosis, and idiopathic pulmonary fibrosis, while also accelerating wound healing. However, more senescent cells are accumulated as organisms age, which exacerbates aging-related diseases. These two contradictory theories inspired us to summarize papers on the restrictive effect of senescence on fibrosis and to input the key findings into simple software that we developed to assist with data organization and presentation. In this review, we illustrate that senescent cells secrete more matrix metalloproteinases to solubilize excess collagen, while chemokines and cytokines activate immune cells to eliminate senescent cells. In the elderly, it is perhaps more effective to limit fibrosis by inducing myofibroblast senescence and then removing senescent cells that are not cleared via normal mechanisms by antisenescence therapies.

Horizontal Gene Transfer has Impacted cox1 Gene Evolution in Cassytha filiformis.

The gene cox1 is one of the most reported mitochondrial genes involved in horizontal gene transfer among angiosperms. However, whether different cox1 copies exist in different populations of a species and whether any other novel way except intron homing exists for cox1 intron acquisition is less understood. In this study, we chose Cassytha filiformis, a parasitic plant from the angiosperm family Lauraceae, as an example to study cox1 variation and evolution. We identified the stable and inheritable co-occurrence of two copies of cox1 genes, which were different in base composition and insertion/deletion among samples of a single species, C. filiformis. The bioinformatic analyses revealed that Type I copy had intact open reading frames, but type II copy had premature stop codons and was a pseudogene. Further INDEL characterization, phylogenetic analyses, and CCT comparisons consistently support two different origins for the two types of C. filiformis cox1 genes. Type I cox1 was likely vertically inherited within the magnoliids but it has captured an intron from another species, whereas the entire type II intron-containing cox1 has most likely been transferred integrally from Cuscuta or other Convolvulaceae species. The finding of the two independent horizontal gene transfer events associated with C. filiformis cox1 genes not only promotes our understanding of the evolutionary history of C. filiformis, but also leaves intriguing evolutionary questions that merits further efforts.

Quinine-modified polymer monolithic column with reversed-phase /strong anion-exchange mixed-mode for pressurized capillary electrochromatography.

Via the facile ring-opening reaction of epoxy groups with quinine, a novel polymer monolith with quaternary ammonium for reversed-phase/strong anion-exchange mixed-mode has been fabricated for pressurized capillary electrochromatography (pCEC). Optimization on the preparation of quinine-modified monoliths has been investigated, and characteristics including morphology, permeability, mechanical stability, reproducibility, and column performance have been also studied. Active quaternary ammonium groups were conveniently produced to generate cationic action sites and stable anodic electroosmotic flow. Multiple interactions including reversed-phase, strong anion-exchange, electrostatic repulsion and π-π stacking interactions were obtained. Satisfactory separation capability of various analytes such as alkylbenzenes, polycyclic aromatic hydrocarbons, benzoic acid and its homologs, and ß2 -receptor excitants has been achieved. Applied to the real sample, the good resolution of three alkaloids in Corydalis yanhusuo were achieved by pCEC with the quinine-modified monolith. The results light a potential access to facilely fabricating quaternary ammonium-functionalized polymer monolith with multiple interactions for efficient electrochromatography profiling of various compounds.

The influence of HK2 blood group antigen on human B cell activation for ABOi-KT conditions.

BACKGROUND: It is well known that ABO blood group system incompatible kidney transplantation (ABOi-KT) is an effective strategy for end-stage renal disease. The main barrier for ABOi-KT is how to keep host B cell activation and blood group antibody titer in low levels. Moreover, the mechanism of B cell activation induced by blood group antigen was unclear in ABOi-KT. RESULTS: In this study, HK2 cells were identified to express blood group B antigen when cocultured with lymphocytes of blood group A. Optical microscope observation demonstrated that HK2 cells in coculture group gradually decreased. Furthermore, flow cytometer assay identified that T cell phenotypes (CD3+, CD3+CD4+ and CD3+CD8+) had no significant change and B cell phenotypes (CD19+ and CD138+) were all significantly enhanced (3.07 and 3.02 folds) at day 4. In addition, immunoturbidimetry analysis demonstrated that blood group B antibody was significantly increased to 2.35 fold at day 4, IgG was significantly increased to 3.60 and 2.81 folds at days 4 and 8 respectively, while IgM had no significant change at the measured time points. CONCLUSIONS: Taken together, B cells were activated and secreted blood group B antibody after treatment with HK2 expressing blood group B antigen. The results of this study maybe useful for further determination of the mechanism of B cell activation after ABO incompatible kidney endothelial cells stimulation.

Lentivirus-mediated over-expression of let-7b microRNA suppresses hepatic fibrosis in the mouse infected with Schistosoma japonicum.

Transforming growth factor-ß (TGF-ß) signaling pathway is documented to participate in liver fibrosis via multifactorial mechanisms. microRNA Let-7b (Let-7b) has been proved to alleviate cell fibrosis through regulating TGF-ß receptor I (TßRI), but whether it is involved in Schistosomiasis liver fibrosis (SLF) has not been determined. In the present, SLF mice model was used to investigate Let-7b's function and mechanism in SLF. We found that hepatic let-7b expression was continuously declined in SLF, accompanied by the induction of TGF-ß pathway molecules (TGF-ß1, TßRI), profibrogenic mediators (α-SMA, colla I), and Th1/Th2 cells response factors (IFN-γ, IL-4). When recombinant Lentivirus of let-7b (Lenti-let-7b) was transfected into S. japonicum-infected mice, the mice hepatic fibrosis was distinctly ameliorated, and TGF-ß1, TßRI, α-SMA, and colla I expressions were remarkly decreased, mice serum IL-4 and IFN-γ levels were reduced. Similarly, over-expression of let-7b down-regulated the expression of TßRI in THP-1 cells transfected with let-7b mimics, while TßRI was up-regulated after treated with let-7b inhibitor. These findings suggested that let-7b is a negative regulator to SLF through downregulating TßRI, and inhibits Th1 and Th2 type cell immune response. This provides a novel potential therapeutic strategy for SFL prevention.

Digital economy, binary factor mismatch and sustainable economic development of coastal areas in China.

In order to promote the sustainable economic development, it is critical employ the digital economy to solve the mismatch dilemma of land and marine factors in coastal areas. It analyzed the influencing mechanisms between the digital economy, land and labor factor mismatch and coastal economic sustainable development using network development and new economic growth theories. The intermediary and regulating effect models were used for empirical tests using panel data from 11 Chinese coastal provinces (city or district) between 2009 and 2018. Results found that: (1) Digital economy promoted the sustainable development of land and marine binary economies in coastal areas; (2) Digital economy improved the factor mismatch of land and marine binary economies, which further affected the sustainable economic development; (3) Market integration is conducive to alleviating land and marine factor mismatch and strengthening the optimization effect of the digital economy on the factor mismatch. This research provides a new perspective for clarifying the mechanism of the digital economy on sustainable economic development, as well as a reference for the realization of rational allocation of factor resources and sustainable economic development by taking factor mismatch of land and marine binary economies and market integration as the intermediary variables and regulatory variables.

Multi-objective location-routing optimization based on machine learning for green municipal waste management.

Most of the existing municipal waste management (MWM) systems focus on the optimization of the waste disposal center locations and waste collection paths, which can be modeled based on the location-routing problem (LRP). This study models a green MWM system by a three-objective location-routing problem to achieve equilibrium among the total cost, carbon emission, and residential satisfaction. The amount of waste demand for each customer is considered as an independent discrete random variable following a normal distribution. The multi-objectives and non-deterministic characteristics make this problem more intractable than the traditional LRP. A multi-objective optimization algorithm based on decision tree classifier is proposed for solving this problem. The decision tree classifier learns from previous searching experience, and then guides the following evolution process to avoid blind searching. The experimental results show that the proposed algorithm has high competitiveness compared with other state-of-art methods. A case study is also conducted for a real waste collection problem in a certain area of Beijing. The proposed method adopts efficient location-routing strategies to balance the total cost, carbon emissions, and distance between residential areas and waste disposal centers.

Treatment of primary epididymal adenocarcinoma: a case report and review of the literature.

BACKGROUND: Epididymal tumors, especially malignant tumors, have low incidence and are rare in our clinical work. However, they may progress quickly and have poor prognosis. For such rare clinical cases with extremely low incidence rates, and as they are prone to misdiagnosis and missed diagnosis and have a very poor prognosis, clinical workers need to pay special attention and consider the possibility of primary epididymal malignant tumors. CASE REPORT: A 63-year-old Chinese male patient from Asia was admitted due to scrotal pain. Upon examination, an abnormal lesion was found in the right epididymal region. After thorough evaluation, surgical resection was performed, and the postoperative pathological result confirmed the presence of epididymal adenocarcinoma. After further ruling out secondary lesions, primary epididymal adenocarcinoma was considered. Right retroperitoneal lymph node dissection was performed under laparoscopic for treatment, and 1/11 lymph node metastasis was detected after surgery. The patient is currently under close follow-up. CONCLUSIONS: The number of clinical cases of primary epididymal malignant tumors is very limited, there is currently no standardized diagnosis and treatment process, and there is a lack of systematic evaluation methods regarding the effectiveness of different treatment options such as chemotherapy, radiotherapy, immunotherapy, and targeted therapy. In addition, the outcome is difficult to predict. In this article, we reviewed relevant literature and systematically elaborated on the diagnosis and treatment of epididymal malignant tumors, hoping to provide useful information for relevant experts.

Effect of bridge height on airflow and aeolian sand flux near surface along the Qinghai-Tibet Railway, China.

In this work, we studied the near-surface flow field structure of railway bridges with different heights through field investigation and wind tunnel simulation experiments. Meanwhile, we simulated the distribution of sand accumulation around a bridge via CFD software based on the sand accumulation around the Basuoqu bridge in the Cuona Lake section of the Qinghai-Tibet Railway. Results show that the sand around this railway bridge is mainly from the lake sediment on the west side of the railway and the weathered detritus on the east side. The height of the railway bridge in the sandy area affects the distribution of the near-surface flow field and the variation in speed on both sides of the bridge. The wind speed trough on both sides of the 6 m high bridge is higher, and the horizontal distance between the wind speed trough and the bridge section is 1.5 times that of the 3 m high bridge. Wind speed attenuates in a certain range on the windward and leeward sides of the bridge, forming an aeolian area; under the beam body, it is affected by the narrow tube effect, forming a wind erosion area. The height of the bridge determines its sand transport capacity. Under certain wind conditions, the overhead area at the bottom of the 3 m high bridge and its two sides do not have the sand transport capacity, so sand accumulates easily. Nevertheless, the sand accumulation phenomenon gradually disappears with the increase in bridge clearance height. The objectives of this study are to reveal the formation mechanism of sand damage for railway bridges, provide theoretical support for the scientific design of railway bridges in sandy areas, and formulate reasonable railway sand prevention measures to ensure the safety of railway running, which have certain theoretical significance and practical value.

Impact of climate change on the global circulation of West Nile virus and adaptation responses: a scoping review.

BACKGROUND: West Nile virus (WNV), the most widely distributed flavivirus causing encephalitis globally, is a vector-borne pathogen of global importance. The changing climate is poised to reshape the landscape of various infectious diseases, particularly vector-borne ones like WNV. Understanding the anticipated geographical and range shifts in disease transmission due to climate change, alongside effective adaptation strategies, is critical for mitigating future public health impacts. This scoping review aims to consolidate evidence on the impact of climate change on WNV and to identify a spectrum of applicable adaptation strategies. MAIN BODY: We systematically analyzed research articles from PubMed, Web of Science, Scopus, and EBSCOhost. Our criteria included English-language research articles published between 2007 and 2023, focusing on the impacts of climate change on WNV and related adaptation strategies. We extracted data concerning study objectives, populations, geographical focus, and specific findings. Literature was categorized into two primary themes: 1) climate-WNV associations, and 2) climate change impacts on WNV transmission, providing a clear understanding. Out of 2168 articles reviewed, 120 met our criteria. Most evidence originated from North America (59.2%) and Europe (28.3%), with a primary focus on human cases (31.7%). Studies on climate-WNV correlations (n = 83) highlighted temperature (67.5%) as a pivotal climate factor. In the analysis of climate change impacts on WNV (n = 37), most evidence suggested that climate change may affect the transmission and distribution of WNV, with the extent of the impact depending on local and regional conditions. Although few studies directly addressed the implementation of adaptation strategies for climate-induced disease transmission, the proposed strategies (n = 49) fell into six categories: 1) surveillance and monitoring (38.8%), 2) predictive modeling (18.4%), 3) cross-disciplinary collaboration (16.3%), 4) environmental management (12.2%), 5) public education (8.2%), and 6) health system readiness (6.1%). Additionally, we developed an accessible online platform to summarize the evidence on climate change impacts on WNV transmission ( https://2xzl2o-neaop.shinyapps.io/WNVScopingReview/ ). CONCLUSIONS: This review reveals that climate change may affect the transmission and distribution of WNV, but the literature reflects only a small share of the global WNV dynamics. There is an urgent need for adaptive responses to anticipate and respond to the climate-driven spread of WNV. Nevertheless, studies focusing on these adaptation responses are sparse compared to those examining the impacts of climate change. Further research on the impacts of climate change and adaptation strategies for vector-borne diseases, along with more comprehensive evidence synthesis, is needed to inform effective policy responses tailored to local contexts.

Releasing Free Anions by High Donor Number Cosolvent in Noncorrosive Electrolytes of Commercially Available Magnesium Salts.

Passivation of the magnesium (Mg) anode in the chloride-free electrolytes using commercially available Mg salts is a critical issue for rechargeable Mg batteries. Herein, a high donor number cosolvent of 1-methylimidazolium (MeIm) is introduced into Mg(TFSI)2- and Mg(HMDS)2-based electrolytes to address the passivation problem and realize highly reversible Mg plating/stripping. Theoretical calculations and experimental characterization results reveal that the strong coordination ability of MeIm with Mg2+ can weaken the anion-cation interactions and promote the formation of free anions that have higher reduction stability, thus significantly suppressing anion-derived passivation layer formation. By adding MeIm cosolvent into Mg(TFSI)2-based electrolyte, the average Coulombic efficiency of the Mg//Cu cell is increased from less than 20% to over 90%, and the Mg//Mg cell can stably cycle for over 800 h with a low overpotential. In the MeIm-regulated Mg(HMDS)2-based electrolyte, the solvation structure change, featured by an effective separation of Mg2+ and HMDS-, greatly increases the ionic conductivity by more than 30 times. This solvation structure regulation strategy for noncorrosive electrolytes of commercially available Mg salts has a great potential for application in future rechargeable Mg metal batteries.

SPI1 exacerbates iron accumulation and promotes osteoclast formation through inhibiting the expression of Hepcidin.

BACKGROUND: Osteoporosis (OP) can be caused by an overactive osteoclastic function. Anti-osteoporosis considerable therapeutic effects in tissue repair and regeneration because bone resorption is a unique osteoclast function. In this study, we mainly explored the underlying mechanisms of osteoclasts' effects on osteoporosis. METHODS: RAW264.7 cells were used and induced toward osteoclast and iron accumulation by M-CSF and RANKL administration. We investigated Hepcidin and divalent metal transporter 1 (DMT1) on iron accumulation and osteoclast formation in an ovariectomy (OVX)-induced osteoporosis. Osteoporosis was induced in mice by OVX, and treated with Hepcidin (10, 20, 40, 80 mg/kg, respectively) and overexpression of DMT1 by tail vein injection. Hepcidin, SPI1, and DMT1 were detected by immunohistochemical staining, western blot and RT-PCR. The bioinformatics assays, luciferase assays, and Chromatin Immunoprecipitation (ChIP) verified that Hepcidin was a direct SPI1 transcriptional target. Iron accumulation was detected by laser scanning confocal microscopy, Perl's iron staining and iron content assay. The formation of osteoclasts was assessed using tartrate-resistant acid phosphatase (TRAP) staining. RESULTS: We found that RAW264.7 cells differentiated into osteoclasts when exposed to M-CSF and RANKL, which increased the protein levels of osteoclastogenesis-related genes, including c-Fos, MMP9, and Acp5. We also observed higher concentration of iron accumulation when M-CSF and RANKL were administered. However, Hepcidin inhibited the osteoclast differentiation cells and decreased intracellular iron concentration primary osteoclasts derived from RAW264.7. Spi-1 proto-oncogene (SPI1) transcriptionally repressed the expression of Hepcidin, increased DMT1, facilitated the differentiation and iron accumulation of mouse osteoclasts. Overexpression of SPI1 significantly declined luciferase activity of HAMP promoter and increased the enrichment of HAMP promoter. Furthermore, our results showed that Hepcidin inhibited osteoclast differentiation and iron accumulation in mouse osteoclasts and OVX mice. CONCLUSION: Therefore, the study revealed that SPI1 could inhibit Hepcidin expression contribute to iron accumulation and osteoclast formation via DMT1 signaling activation in mouse with OVX.

Iron accumulation induced by hepcidin1 knockout accelerates the progression of aging osteoporosis.

OBJECTIVE: Iron accumulation is associated with osteoporosis. This study aims to explore the effect of chronic iron accumulation induced by hepcidin1 deficiency on aging osteoporosis. METHODS: Iron accumulation in hepcidin1 knockout aging mice was assessed by atomic absorption spectroscopy and Perl's staining. Bone microarchitecture was observed using Micro-CT. Hepcidin, ferritin, oxidative stress, and markers of bone turnover in serum were detected by enzyme-linked immunosorbent assay. Bone formation and resorption markers were measured by real-time quantitative PCR. Cell aging was induced by D-galactose treatment. CCK-8, flow cytometry, EdU assays, and Alizarin red staining were performed to reveal the role of hepcidin1 knockout in cell model. Iron Colorimetric Assay Kit and western blot were applied to detect iron and ferritin levels in cells, respectively. RESULTS: In hepcidin1-knockout mice, the ferritin and iron contents in liver and tibia were significantly increased. Iron accumulation induced by hepcidin1 knockout caused a phenotype of low bone mass and deteriorated bone microarchitecture. Osteogenic marker was decreased and osteoclast marker was increased in mice, accompanied by increased oxidative stress level. The mRNA expression levels of osteoclast differentiation markers (RANKL, Mmp9, OPG, Trap, and CTSK) were up-regulated, while bone formation markers (OCN, ALP, Runx2, SP7, and Col-1) were down-regulated in model group, compared to wild type mice. In vitro, hepcidin1 knockdown inhibited proliferation and osteogenic differentiation, while promoted apoptosis, with increased levels of iron and ferritin. CONCLUSION: Iron accumulation induced by hepcidin1 deficiency aggravates the progression of aging osteoporosis via inhibiting osteogenesis and promoting osteoclast genesis.