Enhanced sorption and destruction of PFAS by biochar-enabled advanced reduction process.

The biochar-enabled advanced reduction process (ARP) was developed for enhanced sorption (by biochar) and destruction of PFAS (by ARP) in water. First, the biochar (BC) was functionalized by iron oxide (Fe3O4), zero valent iron (ZVI), and chitosan (chi) to produce four biochars (BC, Fe3O4-BC, ZVI-chi-BC, and chi-BC) with improved physicochemical properties (e.g., specific surface area, pore structure, hydrophobicity, and surface functional groups). Batch sorption experimental results revealed that compared to unmodified biochar, all modified biochars showed greater sorption efficiency, and the chi-BC performed the best for PFAS sorption. The chi-BC was then selected to facilitate reductive destruction and defluorination of PFAS in water by ARP in the UV-sulfite system. Adding chi-BC in UV-sulfite ARP system significantly enhanced both degradation and defluorination efficiencies of PFAS (up to ∼100% degradation and ∼85% defluorination efficiencies). Radical analysis using electron paramagnetic resonance (EPR) spectroscopy showed that sulfite radicals dominated at neutral pH (7.0), while hydrated electrons (eaq-) were abundant at higher pH (11) for the efficient destruction of PFAS in the ARP system. Our findings elucidate the synergies of biochar and ARP in enhancing PFAS sorption and degradation, providing new insights into PFAS reductive destruction and defluorination by different reducing radical species at varying pH conditions.

Counteractive effects of predator invasion and habitat destruction on predator-prey systems.

Alien species invasion and habitat destruction are among the primary threats to native animal communities, particularly for native predator-prey systems. However, when predator invasion and habitat destruction co-occur, it remains unclear whether their respective threats to native systems compensate each other or accumulate, as well as how these effects respond to the different characteristics of predator invasion and habitat destruction. In this study, we developed a spatially explicit simulation model with one prey species and one predator species and exposed it to invasive predators and habitat destruction with different properties. The results revealed the following insights: (1) Habitat destruction can compensate threats to native predator-prey systems from global predator invasion only when native predators possess predation capability similar to those of the invaders. In other scenarios, cumulative effects arise from predator invasion and habitat destruction. (2) Low levels of habitat destruction occurring at a faster rate, in conjunction with a substantial number of global invasive predators being present, can better compensate their respective threats to native predator-prey systems than the other scenarios. These findings provide valuable insights into situations where habitat destruction and alien species invasion coincide. They raise the question of whether we can leverage the interaction between them to reduce threats to biodiversity.

Cardiac gene delivery using ultrasound: State of the field.

Over the past two decades, there has been tremendous and exciting progress toward extending the use of medical ultrasound beyond a traditional imaging tool. Ultrasound contrast agents, typically used for improved visualization of blood flow, have been explored as novel non-viral gene delivery vectors for cardiovascular therapy. Given this adaptation to ultrasound contrast-enhancing agents, this presents as an image-guided and site-specific gene delivery technique with potential for multi-gene and repeatable delivery protocols-overcoming some of the limitations of alternative gene therapy approaches. In this review, we provide an overview of the studies to date that employ this technique toward cardiac gene therapy using cardiovascular disease animal models and summarize their key findings.

Modeling green energy and innovation for ecological risk management using second generation dynamic quantile panel data model.

Ecological risk management has emerged as a critical research and policy development area in energy and environmental economics. Sustained ecology is crucial for the standard of living and food security. As the adverse impacts of environmental degradation and climate change become increasingly apparent it is imperative to understand ecological risk and its interconnectedness with environmental pressure, clean energy, economic activity, globalization, and green technology. Ecological risk is assessed using the environmental performance index which is a holistic indicator of climate change, environmental pressures and human actions in which most of these indicators have spatial effects. This paper explores the multifaceted relationship between identified anthropogenic critical factors and their role in effectively managing ecological risk globally. This study has developed the second-generation dynamic panel quantile regression considering spatial effects of economic activities on ecology across borders of 55 countries between 1995 and 2022. This innovative hybrid estimation scheme that integrated theoretical and econometric aspects makes the model robust to major regression issues. Several implications ranked in decreasing order of its effectiveness are reducing environmental pressure, expediting energy transition, and embracing economic integration while there is a need to work on rejuvenating green technology and green growth.

Ewing Sarcoma of the Larynx with Thyroid Cartilage Destruction: A Case Report.

Ewing sarcoma of the larynx is extremely rare, only a few number of cases have been reported. In this report, we describe a case of extraskeletal Ewing sarcoma of the larynx with thyroid cartilage destruction. Laryngoscope, 2024.

YTHDF1 promotes the osteolytic bone metastasis of breast cancer via inducing EZH2 and CDH11 translation.

Bone metastasis is common in breast cancer and more effective therapies are required, however, its molecular mechanism is poorly understood. Additionally, the role of the m6A reader YTHDF1 in bone metastasis of breast cancer has not been reported. Here, we reveal that the increased expression of YTHDF1 is clinically correlated with breast cancer bone metastases. YTHDF1 promotes migration, invasion, and osteoblast adhesion and induces osteoclast differentiation of cancer cells in vitro and vivo. Mechanically, RNA-seq, MeRIP-seq and RIP-seq analysis, and molecular biology experiments demonstrate that YTHDF1 translationally enhances EZH2 and CDH11 expression by reading m6A-enriched sites of their transcripts. Moreover, adeno-associated virus (AAV) was used to deliver shYTHDF1 (shYTHDF1-AAV) in intratibial injection models, eliciting a significant suppressive effect on breast cancer bone metastatic formation and osteolytic destruction. Overall, we uncovered that YTHDF1 promotes osteolytic bone metastases of breast cancer by inducing EZH2 and CDH11 translation.

Enhancing the Thermal Mineralization of Perfluorooctanesulfonate on Granular Activated Carbon Using Alkali and Alkaline-Earth Metal Additives.

Thermal treatment has emerged as a promising approach for either the end-of-life treatment or regeneration of granular activated carbon (GAC) contaminated with per- and polyfluoroalkyl substances (PFAS). However, its effectiveness has been limited by the requirement for high temperatures, the generation of products of incomplete destruction, and the necessity to scrub HF in the flue gas. This study investigates the use of common alkali and alkaline-earth metal additives to enhance the mineralization of perfluorooctanesulfonate (PFOS) adsorbed onto GAC. When treated at 800 °C without an additive, only 49% of PFOS was mineralized to HF. All additives tested demonstrated improved mineralization, and Ca(OH)2 had the best performance, achieving a mineralization efficiency of 98% in air or N2. Its ability to increase the reaction rate and shift the byproduct selectivity suggests that its role may be catalytic. Moreover, additives reduced HF in the flue gas by instead reacting with the additive to form inorganic fluorine (e.g., CaF2) in the starting waste material. A hypothesized reaction mechanism is proposed that involves the electron transfer from O2- defect sites of CaO to intermediates formed during the thermal decomposition of PFOS. These findings advocate for the use of additives in the thermal treatment of GAC for disposal or reuse, with the potential to reduce operating costs and mitigate the environmental impact associated with incinerating PFAS-laden wastes.

Regulation of IFP in solid tumours through acoustic pressure to enhance infiltration of nanoparticles of various sizes.

Numerous nanomedicines have been developed recently that can accumulate selectively in tumours due to the enhanced permeability and retention (EPR) effect. However, the high interstitial fluid pressure (IFP) in solid tumours limits the targeted delivery of nanomedicines. We were previously able to relieve intra-tumoural IFP by low-frequency non-focused ultrasound (LFNFU) through ultrasonic targeted microbubble destruction (UTMD), improving the targeted delivery of FITC-dextran. However, the accumulation of nanoparticles of different sizes and the optimal acoustic pressure were not evaluated. In this study, we synthesised Cy5.5-conjugated mesoporous silica nanoparticles (Cy5.5-MSNs) of different sizes using a one-pot method. The Cy5.5-MSNs exhibited excellent stability and biosafety regardless of size. MCF7 tumour-bearing mice were subjected to UTMD over a range of acoustic pressures (0.5, 0.8, 1.5 and 2.0 MPa), and injected intravenously with Cy5.5-MSNs. Blood perfusion, tumour IFP and intra-tumoural accumulation of Cy5.5-MSNs were analysed. Blood perfusion and IFP initially rose, and then declined, as acoustic pressure intensified. Furthermore, UTMD significantly enhanced the accumulation of differentially sized Cy5.5-MSNs in tumour tissues compared to that of the control group, and the increase was sevenfold higher at an acoustic pressure of 1.5 MPa. Taken together, UTMD enhanced the infiltration and accumulation of Cy5.5-MSNs of different sizes in solid tumours by reducing intra-tumour IFP.

Acacetin targets STING to alleviate the destabilization of the medial meniscus-induced osteoarthritis in mice.

Osteoarthritis (OA) is a common joint disorder affecting about 7% of the global population, primarily characterized by the gradual loss of articular cartilage. This degeneration results from local inflammation, matrix depletion, and direct cartilage damage. A critical element in this process is the activation of the stimulator of the interferon genes (STING) pathway. Emerging evidence highlights its potential as a therapeutic target, with natural products showing promise as inhibitors. Our study centers on Acacetin, a basic unit of polyketides known for its anti-inflammatory properties. Prior research has highlighted its potential interaction with STING based on the structure. Thus, this study aimed to assess the effectiveness of Acacetin as a STING inhibitor and its protective role against OA. In vitro experiments showed that Acacetin pretreatment not only mitigated interleukin-1ß (IL-1ß)-induced cytotoxicity but also decreased the inflammatory response and degeneration in chondrocytes stimulated IL-1ß. In vivo studies revealed that Acacetin administration significantly reduced articular cartilage destruction, abnormal bone remodeling, and osteophyte formation in a model of OA induced by destabilization of the medial meniscus (DMM). Mechanistically, Acacetin was found to interact directly with STING, and inhibit IL-1ß-induced activation of STING, along with the subsequent phosphorylation of the TBK1/NF-κB pathway in chondrocytes. In conclusion, our findings establish Acacetin as an effective inhibitor of STING that protects chondrocytes from IL-1ß-induced damage and slows the progression of OA in mice.

Inflammatory diseases causing joint and bone destruction: rheumatoid arthritis and hemophilic arthropathy.

Various diseases and conditions cause joint disorders. Osteoarthritis (OA) is characterized by the degeneration of articular cartilage, synovitis, and anabolic changes in surrounding bone tissues. In contrast, rheumatoid arthritis (RA) and hemophilic arthropathy (HA) display marked destruction of bone tissues caused by synovitis. RA is a representative autoimmune disease. The primary tissue of RA pathogenesis is the synovial membrane and involves various immune cells that produce catabolic cytokines and enzymes. Hemophilia is a genetic disorder caused by a deficiency in blood clotting factors. Recurrent intra-articular bleeding leads to chronic synovitis through excessive iron deposition and results in the destruction of affected joints. Although the triggers for these two joint diseases are completely different, many cytokines and enzymes are common in the pathogenesis of both RA and HA. This review focuses on the similarities between joint and bone destruction in RA and HA. The insights may be useful in developing better treatments for hemophilia patients with arthropathy and osteoporosis by leveraging advanced therapeutics for RA.

Toll-like receptor 4 deficiency affects the balance of osteoclastogenesis and osteoblastogenesis in periodontitis.

Toll-like receptor 4 (TLR4) acts as a double-edged sword in the occurrence and development of periodontitis. While the activation of TLR4 in macrophages aids in clearing local pathogens, it can also disrupt innate immune responses, upsetting microecological balance and accelerating the destruction of periodontal bone tissues. To date, the effects of TLR4 on osteogenesis and osteoclastogenesis in periodontitis have not been comprehensively studied. In this study, we investigated the development of periodontitis in the Tlr4-/- mice by ligating their second molars with silk threads. Compared to wild-type (WT) mice, Tlr4-/- mice demonstrated increased resistance to periodontitis-associated bone destruction, as evidenced by decreased bone resorption and enhanced bone regeneration. Mechanistically, the deletion of Tlr4 not only inhibited osteoclast formation by reducing the expression of NFATc1, CTSK and TRAP, but also enhanced osteogenic abilities through increased expression of OCN, OPN and RUNX2. In conclusion, TLR4 tips the balance of osteoclastogenesis and osteogenesis, thereby promoting periodontal bone destruction in periodontitis.

Ultrasound-targeted microbubble destruction facilitates cartilage repair through increased the migration of mesenchymal stem cells via HIF-1α-mediated glycolysis pathway in rats.

OBJECTIVE: Mesenchymal stem cells (MSCs) can treat osteoarthritis (OA), but their therapeutic efficacy is poor to date due to low migration efficiency. This study aimed to determine whether ultrasound-targeted microbubble destruction (UTMD) could ameliorate cartilage repair efficiency through facilitating the migration of MSCs via hypoxia-inducible factor-1α (HIF-1α)-mediated glycolysis regulatory pathway in OA model rats. METHODS: OA rats were treated with MSCs alone or in combination with UTMD, respectively, for 4 weeks. Cartilage histopathology, MSCs migration efficiency, von Frey fiber thresholds, and the expression levels of collagen II and MMP-13 were measured. Further, MSCs were extracted from the bone marrow of rats, cocultured with osteoarthritic chondrocytes, transfected to siRNA-HIF-1α, and subjected to UTMD for 4 days. Glucose consumption, lactate production, and cell migration efficiency were assessed. The protein expression levels of HIF-1α, HK2, PKM2, and GLUT1 were measured, respectively. RESULTS: In OA rat model, NC-MSCs + UTMD improved migration efficiency, increased collagen II expression, decreased MMP-13 expression, and delayed osteoarthritis progression. Silencing HIF-1α attenuated the effects induced by UTMD. In vitro, UTMD led to increases in MSC activity and migration, glucose consumption, lactate production, and the protein expression of HIF-1α, HK2, PKM2, and GLUT1 expression, all of which were reversed upon HIF-1α silencing. CONCLUSION: UTMD enhances MSCs migration and improves cartilage repair efficiency through the HIF-1α-mediated glycolytic regulatory pathway, providing a novel therapy strategy for knee osteoarthritis.

Unlocking novel therapeutic avenues in glioblastoma: Harnessing 4-amino cyanine and miRNA synergy for next-gen treatment convergence.

Glioblastoma (GBM) poses a formidable challenge in oncology due to its aggressive nature and dismal prognosis, with average survival rates around 15 months despite conventional treatments. This review proposes a novel therapeutic strategy for GBM by integrating microRNA (miRNA) therapy with 4-amino cyanine molecules possessing near-infrared (NIR) properties. miRNA holds promise in regulating gene expression, particularly in GBM, making it an attractive therapeutic target. 4-amino cyanine molecules, especially those with NIR properties, have shown efficacy in targeted tumor cell degradation. The combined approach addresses gene expression regulation and precise tumor cell degradation, offering a breakthrough in GBM treatment. Additionally, the review explores noncoding RNAs classification and characteristics, highlighting their role in GBM pathogenesis. Advanced technologies such as antisense oligonucleotides (ASOs), locked nucleic acids (LNAs), and peptide nucleic acids (PNAs) show potential in targeting noncoding RNAs therapeutically, paving the way for precision medicine in GBM. This synergistic combination presents an innovative approach with the potential to advance cancer therapy in the challenging landscape of GBM.

The effects of local variations in conditions on carbon storage and release in the continental mantle.

Recent advances indicate that the amount of carbon released by gradual degassing from the mantle needs to be revised upwards, whereas the carbon supplied by plumes may have been overestimated in the past. Variations in rock types and oxidation state may be very local and exert strong influences on carbon storage and release mechanisms. Deep subduction may be prevented by diapirism in thick sedimentary packages, whereas carbonates in thinner sequences may be subducted. Carbonates stored in the mantle transition zone will melt when they heat up, recognized by coupled stable isotope systems (e.g. Mg, Zn, Ca). There is no single 'mantle oxygen fugacity', particularly in the thermal boundary layer (TBL) and lowermost lithosphere, where very local mixtures of rock types coexist. Carbonate-rich melts from either subduction or melting of the uppermost asthenosphere trap carbon by redox freezing or as carbonate-rich dykes in this zone. Deeply derived, reduced melts may form further diamond reservoirs, recognized as polycrystalline diamonds associated with websteritic silicate minerals. Carbon is released by either edge-driven convection, which tears sections of the TBL and lower lithosphere down so that they melt by a mixture of heating and oxidation, or by lateral advection of solids beneath rifts. Both mechanisms operate at steps in lithosphere thickness and result in carbonate-rich melts, explaining the spatial association of craton edges and carbonate-rich magmatism. High-pressure experiments on individual rock types, and increasingly on reactions between rocks and melts, are fine-tuning our understanding of processes and turning up unexpected results that are not seen in studies of single rocks. Future research should concentrate on elucidating local variations and integrating these with the interpretation of geophysical signals. Global concepts such as average sediment compositions and a uniform mantle oxidation state are not appropriate for small-scale processes; an increased focus on local variations will help to refine carbon budget models.

Synergic effect of combined xenogeneic mesenchymal stem cells and ceftriaxone on acute septic arthritis.

BACKGROUND: This study tested the hypothesis that combined ceftriaxone (Cef) and human umbilical cord-derived mesenchymal stem cells (HUCDMSCs) was better than either therapy for alleviating acute septic arthritis (ASA). METHODS AND RESULTS: Adult-male C57BL/6 mice were categorized into control group (Clt), group A (ASA only), group B [ASA + Cef (5 mg/kg, IM per day, at days 2 to 16 after ASA induction)], group C [ASA + HUCDMSCs (5 × 105 per mice at days 2, 3, 4 after ASA induction)], and group D (ASA + Cef + HUCDMSCs). Animals were euthanized by day 28. The result demonstrated that the body weight was significantly lower, whereas the ratio of kidney or spleen weight to WB, circulatory WBC count, bacterial colony-formation-unit from circulatory/kidney extraction were significantly higher in group A than in other groups (all P < .001). The proinflammatory cytokines (IL-6/TNF-α) of knee joint fluid were lowest in Clt and significantly and progressively reduced from groups A to D, whereas the circulatory levels of these 2 parameters at the time points of days 3/7/28 exhibited an identical pattern as knee joint fluid among the groups (all P-value < .0001). The scores of vertebral-bone destructions/inflamed synovium were lowest in Clt, highest in group A, significantly higher in group C than in groups B/D, and significantly higher in group C than in group D (all P < .0001). CONCLUSION: Combined antibiotics and Cef and HUCDMSCs was superior to just one therapy for suppressing circulatory and tissue levels of inflammation and knee joint destruction in ASA.

Differential alterations of CXCR3, CXCR5 and CX3CR1 in patients with immune thrombocytopenia.

As a versatile element for maintaining homeostasis, the chemokine system has been reported to be implicated in the pathogenesis of immune thrombocytopenia (ITP). However, research pertaining to chemokine receptors and related ligands in adult ITP is still limited. The states of several typical chemokine receptors and cognate ligands in the circulation were comparatively assessed through various methodologies. Multiple variable analyses of correlation matrixes were conducted to characterize the correlation signatures of various chemokine receptors or candidate ligands with platelet counts. Our data illustrated a significant decrease in relative CXCR3 expression and elevated plasma levels of CXCL4, 9-11, 13, and CCL3 chemokines in ITP patients with varied platelet counts. Flow cytometry assays revealed eminently diminished CXCR3 levels on T and B lymphocytes and increased CXCR5 on cytotoxic T cell (Tc) subsets in ITP patients with certain platelet counts. Meanwhile, circulating CX3CR1 levels were markedly higher on T cells with a concomitant increase in plasma CX3CL1 level in ITP patients, highlighting the importance of aberrant alterations of the CX3CR1-CX3CL1 axis in ITP pathogenesis. Spearman's correlation analyses revealed a strong positive association of peripheral CXCL4 mRNA level, and negative correlations of plasma CXCL4 concentration and certain chemokine receptors with platelet counts, which might serve as a potential biomarker of platelet destruction in ITP development. Overall, these results indicate that the differential expression patterns and distinct activation states of peripheral chemokine network, and the subsequent expansion of circulating CXCR5+ Tc cells and CX3CR1+ T cells, may be a hallmark during ITP progression, which ultimately contributes to thrombocytopenia in ITP patients.

Huangqi Guizhi Wuwu Decoction suppresses inflammation and bone destruction in collagen-induced arthritis mice.

Objective: Rheumatoid arthritis (RA) is a chronic inflammatory and destructive arthritis, characterized by inflammatory infiltration and bone destruction. Huangqi Guizhi Wuwu Decoction (HGWD) is traditional Chinese medicine, which has been applied in the treatment of RA in clinical. The aim of this study was to investigate the therapeutic effect of HGWD on collagen-induced arthritis (CIA) mouse model. Methods: DBA/1J female mice were used to establish the collagen-induced arthritis (CIA) model. HGWD was administered intragastrically once a day for four weeks starting on the 22nd day after the first immunization. The body weight, hind paw thickness and clinical score were measured every five days. Gait analysis, histopathological staining, enzyme-linked immunosorbent assay (ELISA), ultrasound imaging and micro-computed tomography imaging were performed to determine the effects of HGWD treatment on inflammation and bone structure in this model. Moreover, Real-time PCR and Western blot analysis were used to detect inflammatory factors mRNA and protein levels after HGWD intervention in RAW 264.7 cells. Results: HGWD attenuated symptoms of arthritis, suppressed inflammatory synovium area and the serum levels of inflammatory factors, inhibited joint space enlargement in the knee and ankle joints, reduced numbers of osteoclasts, protected bone destruction, as well as improved motor function. HGWD decreased the expression of mRNA for inflammatory factors and the protein expression levels of p-NF-кB and IL-17. Conclusion: These results suggested that HGWD suppresses inflammation, attenuates bone erosion and maintains motor function in collagen-induced arthritis mice.

Interactive effects of drought and deforestation on multitrophic communities and aquatic ecosystem functions in the Neotropics-a test using tank bromeliads.

Background: Together with the intensification of dry seasons in Neotropical regions, increasing deforestation is expected to exacerbate species extinctions, something that could lead to dramatic shifts in multitrophic communities and ecosystem functions. Recent studies suggest that the effects of habitat loss are greater where precipitation has decreased. Yet, experimental studies of the pure and interactive effects of drought and deforestation at ecosystem level remain scarce. Methods: Here, we used rainshelters and transplantation from rainforest to open areas of natural microcosms (the aquatic ecosystem and microbial-faunal food web found within the rainwater-filled leaves of tank bromeliads) to emulate drought and deforestation in a full factorial experimental design. We analysed the pure and interactive effects of our treatments on functional community structure (including microorganisms, detritivore and predatory invertebrates), and on leaf litter decomposition in tank bromeliad ecosystems. Results: Drought or deforestation alone had a moderate impact on biomass at the various trophic level, but did not eliminate species. However, their interaction synergistically reduced the biomass of all invertebrate functional groups and bacteria. Predators were the most impacted trophic group as they were totally eliminated, while detritivore biomass was reduced by about 95%. Fungal biomass was either unaffected or boosted by our treatments. Decomposition was essentially driven by microbial activity, and did not change across treatments involving deforestation and/or drought. Conclusions: Our results suggest that highly resistant microorganisms such as fungi (plus a few detritivores) maintain key ecosystem functions in the face of drought and habitat change. We conclude that habitat destruction compounds the problems of climate change, that the impacts of the two phenomena on food webs are mutually reinforcing, and that the stability of ecosystem functions depends on the resistance of a core group of organisms. Assuming that taking global action is more challenging than taking local-regional actions, policy-makers should be encouraged to implement environmental action plans that will halt habitat destruction, to dampen any detrimental interactive effect with the impacts of global climate change.