Understanding phosphorus mobilization mechanisms in acidic soil amended with calcium-silicon-magnesium-potassium fertilizer.

Calcium-silicon-magnesium-potassium fertilizer (CSMP) is usually used as an amendment to counteract soil acidification caused by historical excessive nitrogen (N) applications. However, the impact of CSMP addition on phosphorus (P) mobilization in acidic soils and the related mechanisms are not fully understood. Specifically, a knowledge gap exists with regards to changes in soil extracellular enzymes that contribute to P release. Such a knowledge gap was investigated by an incubation study with four treatments: i) initial soil (Control), ii) urea (60 mg kg-1) addition (U); iii) CSMP (1%) addition (CSMP) and iv) urea (60 mg kg-1) and CSMP (1%) additions (U + CSMP). Phosphorus mobilization induced by different processes was distinguished by biologically based P extraction. The Langmuir equation, K edge X-ray absorption near-edge structure spectroscopy, and ecoenzyme vector analysis according to the extracellular enzyme activity stoichiometry were deployed to investigate soil P sorption intensity, precipitation species, and microbial-driven turnover of organophosphorus. Results showed that CaCl2 extractable P (or citric acid extractable P) content increased by 63.4% (or 39.2%) in the soil with CSMP addition, compared with the study control. The accelerated mobilization of aluminum (Al)/iron (Fe)-bound P after CSMP addition, indicated by the reduction of the sum of FePO4·2H2O and AlPO4 proportion, contributed to this increase. The decrease of P sorption capacity can also be responsible for it. The CSMP addition increased enzyme extractable P in the soil nearly 7-fold and mitigated the limitations of carbon (C) and P for soil microorganisms (indicated by the enzyme stoichiometry and ecoenzyme vector analysis), suggesting that microbial turnover processes also contribute to P mobilization in amended acidic soil. These findings indicate that the P mobilization in CSMP amended acidic soil not only attributed to both decreasing P sorption capacity and dissolving phosphate precipitation, but also to the increase of the microbial turnover of the organophosphorus pool.

Hydrogenated silicene nanosheet functionalized scaffold enables immuno-bone remodeling.

An ideal implant needs to have the ability to coordinate the foreign body response and tissue regeneration. Here, Hydrogenated-silicon nanosheets (H-Si NSs) with favorable biodegradability are integrated and functionalized into a ß-tricalcium phosphate scaffold (H-Si TCP) for bone defect healing. H-Si TCP can greatly improve bone regeneration through osteoimmunomodulation-guided biodegradation in vivo. The spatiotemporal regulation of degradation products replenishes sufficient nutrients step by step for the entire process of bone repair. Extracellular and intracellular reactive oxygen species (ROS) are first downregulated by reaction with H-Si NSs, followed by marked M2 polarization, remodeling the micro-environment timely for immune-bone regeneration. The release of primary reaction products awakened bone marrow mesenchymal stem cells (BMSCs), which are converted into osteoblasts anchored on scaffolds. Subsequently, biomineralization is promoted by the final degradation products. The intrinsic ROS-responsive, immunoregulatory, and osteo-promotive capability of 2D H-Si NSs makes such composite H-Si TCP scaffold a highly potential alternative for the treatment of critical bone defect.

Natural and biocompatible dressing unit based on tea carbon dots modified core-shell electrospun fiber for diabetic wound disinfection and healing.

Wound infection and healing in patients with diabetes is one of the complex problems in trauma treatment. Therefore, designing and preparing an advanced dressing membrane for treating the wounds of such patients is essential. In this study, a zein film with biological tea carbon dots (TCDs) and calcium peroxide (CaO2) as the main components for promoting diabetic wound healing was prepared by an electrospinning technique, which combines the advantages of natural degradability and biosafety. CaO2 is a biocompatible material with a microsphere structure that reacts with water to release hydrogen peroxide and calcium ions. TCDs with a small diameter were doped in the membrane to mitigate its properties while improving the antibacterial and healing effects of the membrane. TCDs/CaO2 was mixed with ethyl cellulose-modified zein (ZE) to prepare the dressing membrane. The antibacterial properties, biocompatibility and wound-healing properties of the composite membrane were investigated by antibacterial experiment, cell experiment and a full-thickness skin defect. TCDs/CaO2 @ZE exhibited significant anti-inflammatory and wound healing-promoting properties in diabetic rats, without any cytotoxicity. This study is meaningful in developing a natural and biocompatible dressing membrane for diabetic wound healing, which shows a promising application in wound disinfection and recovery in patients with chronic diseases.

Enhanced phosphorus fixation in red mud-amended acidic soil subjected to periodic flooding-drying and straw incorporation.

Globally, red mud is a solid waste from the aluminum industry, which is rich in iron oxides. It is an effective soil amendment in agriculture that protects connected waters from legacy diffuse phosphorus (P) soil losses. However, other management practices such as flooding and drying and/or organic carbon inputs could potentially alter P fixation in these red mud-amended soils thereby releasing P to waters. The present study was designed and conducted to monitor the mobilization of P in a red mud-amended acidic soil subjected to periodic flooding-drying, straw incorporation, and a mix of both management practices. Sequential extraction and K edge X-ray absorption near-edge structure spectroscopy (k-XANES) were employed to distinguish P fractions/species and the Langmuir model was fitted to evaluate soil P sorption capacity. The content of labile P indicated by CaCl2-P was increased significantly by 101% and 28.7% in the straw incorporation and periodic flooding-drying treatments, while it decreased significantly by 22.3% in the combined periodic flooding-drying with straw incorporation treatment, compared with Control. The inherent phosphate contained in sorghum straw, and the enhanced iron (Fe) reduction and dissolution of Calcium (Ca)-bound P induced by straw addition contributed to mobilization of P in the straw incorporation treatment. In contrast, the increased poorly crystalline Al/Fe oxides-bound P and occluded Fe-bound P fraction in the combined periodic flooding-drying with straw incorporation treatment explains the decrease in CaCl2-P. Furthermore, the increased soil P sorption capacity and the decreased P desorption rate were also responsible for the reduced P loss risk in the treatment. The results of structural equation modelling (SEM) indicated that organically complexed Fe and Fe-bound P were directly affecting P mobilization in the amended soil. Overall, the present study shows that appropriate flooding-drying events coupled with straw incorporation could be a mitigation practice for stabilizing P in red mud-amended soil. However, before it can be applied on a wide scale, multi-point and field trials should be carried out to further evaluate actual environmental implications.

A Real-Time Memory Updating Strategy for Unsupervised Person Re-Identification.

Recently, clustering-based methods have been the dominant solution for unsupervised person re-identification (ReID). Memory-based contrastive learning is widely used for its effectiveness in unsupervised representation learning. However, we find that the inaccurate cluster proxies and the momentum updating strategy do harm to the contrastive learning system. In this paper, we propose a real-time memory updating strategy (RTMem) to update the cluster centroid with a randomly sampled instance feature in the current mini-batch without momentum. Compared to the method that calculates the mean feature vectors as the cluster centroid and updating it with momentum, RTMem enables the features to be up-to-date for each cluster. Based on RTMem, we propose two contrastive losses, i.e., sample-to-instance and sample-to-cluster, to align the relationships between samples to each cluster and to all outliers not belonging to any other clusters. On the one hand, sample-to-instance loss explores the sample relationships of the whole dataset to enhance the capability of density-based clustering algorithm, which relies on similarity measurement for the instance-level images. On the other hand, with pseudo-labels generated by the density-based clustering algorithm, sample-to-cluster loss enforces the sample to be close to its cluster proxy while being far from other proxies. With the simple RTMem contrastive learning strategy, the performance of the corresponding baseline is improved by 9.3% on Market-1501 dataset. Our method consistently outperforms state-of-the-art unsupervised learning person ReID methods on three benchmark datasets. Code is made available at:https://github.com/PRIS-CV/RTMem.

Understanding the relative contributions of fungi and bacteria led nitrous oxide emissions in an acidic soil amended with industrial waste.

Amendment of fertilized arable soil with alkaline industrial waste has the potential to ameliorate soil acidification whilst also improving crop yield. Another co-benefit is nitrous oxide (N2O) emission abatement but the contribution of fungi and bacteria involved in this process remains unclear. Two incubation experiments were conducted to: 1) examine how amendment of acidic soils with a mixture of phosphorus tailings mixture and insoluble potassium-containing rocks (PT) affect N2O emissions and 2) understand the microbial mechanisms and relative contributions of fungi and bacteria responsible for N2O emissions. In the first incubation experiment, the four treatments consisted of: i) the study control, ii) urea, iii) PT amendment and iv) PT amendment plus urea. Results showed that the PT amendment significantly increased soil pH from 4.8 to above 6.0, and reduced N2O emissions by 65.7%. PT-amended soils had higher N2 emissions and faster O2 consumption. The PT amendment significantly increased extracellular enzyme activities of leucine aminopeptidase and N-Acetyl-ß-glucosaminidase, while it significantly decreased activities of ß-1, 4-glucosidase and ß-cellobiosidase. Two antibiotics (cycloheximide and streptomycin) combined with substrate-induced respiration method were used in the second incubation experiment. Compared to soil with urea, urea with PT amendment raised soil bacteria-related N2O from 9.2% to 18.8% while decreasing fungi-related N2O from 50.5% to 43.2%. These findings suggest that the N2O emissions from acidic soils can be considerably mitigated by the application of alkaline industrial wastes. The contribution of fungi should be considered when designing and applying N2O mitigation strategies in acidic soils. DATA AVAILABILITY: Data will be made available on request.

Less sclerotic microarchitecture pattern with increased bone resorption in glucocorticoid-associated osteonecrosis of femoral head as compared to alcohol-associated osteonecrosis of femoral head.

Background: Glucocorticoid usage and alcohol abuse are the most widely accepted risk factors for nontraumatic osteonecrosis of femoral head (ONFH). Despite distinct etiologies between glucocorticoid-associated ONFH (GONFH) and alcohol-associated ONFH (AONFH), little is known about the differences of the microarchitectural and histomorphologic characteristics between these subtypes of ONFH. Purposes: To investigate bone microarchitecture, bone remodeling activity and histomorphology characteristics of different regions in femoral heads between GONFH and AONFH. Methods: From September 2015 to October 2020, 85 patients diagnosed with GONFH and AONFH were recruited. Femoral heads were obtained after total hip replacement. Femoral head specimens were obtained from 42 patients (50 hips) with GONFH and 43 patients (50 hips) with AONFH. Micro-CT was utilized to assess the microstructure of 9 regions of interest (ROIs) in the femoral head. Along the supero-inferior orientation, the femoral head was divided into necrotic region, reactive interface, and normal region; along the medio-lateral orientation, the femoral head was divided into medial region, central region and lateral region. Decalcified and undecalcified bone histology was subsequently performed to evaluate histopathological alterations and bone remodeling levels. Results: In the necrotic region, most of the microarchitectural parameters did not differ significantly between GONFH and AONFH, whereas both the reactive interface and normal region revealed a less sclerotic microarchitecture but a higher bone remodeling level in GONFH than AONFH. Despite similar necrotic pathological manifestations, subchondral trabecular microfracture in the necrotic region was more severe and vasculature of the reactive interface was more abundant in GONFH. Conclusions: GONFH and AONFH shared similar microarchitecture and histopathological features in the necrotic region, while GONFH exhibited a less sclerotic microarchitecture and a more active bone metabolic status in both the reactive interface and normal region. These differences between GONFH and AONFH in bone microarchitectural and histopathological characteristics might contribute to the development of disease-modifying prevention strategies and treatments for ONFH, taking into etiologies.

Environmental and economic benefits of substituting chemical potassium fertilizer with crop straw residues in China.

Chemical potassium (K) fertilizer plays a crucial role in improving crop productivity, yet its production and application also result in environmental issues including greenhouse gas emission and atmospheric pollution emissions. In addition, the abandon or open burning of crop straw not only causes the wasting of resource, but also creates environmental problems. On-present studies recognize the importance of the substitution of straw resource utilization for chemical K fertilizer, yet whether such action can effectively mitigate the emissions of greenhouse gas and pollutants remains unclear. In this study, we examine the effects of substituting straw for chemical K fertilizer on the emissions of greenhouse gas and pollutants and the associated direct and damage cost implications in China at the provincial level. Results showed that the useable straw contributed 2750 Gg of K from 2000 to 2009 and 3567 Gg from 2010 to 2017, equaling 121% and 57.3% of chemical K fertilizer, respectively. Chemical K fertilizer substitution with straw can also reduce annual emissions of greenhouse gases, ammonia, nitrogen oxide, and fine particulate matter by 664 Gg, 18.5 Gg, 10.7 Gg, and 1.48 Gg, respectively. The average abatement cost reached 4790 million USD during 2000-2009 and 3898 million USD during 2010-2017, respectively. And the mitigation potential of the emissions of greenhouse gas and pollutants and average abatement cost showed a large spatial heterogeneity at the provincial level. Overall, replacing chemical K fertilizer with straw is an efficient strategy to reduce environmental risk and utilize agricultural waste.

Supplying amendments alleviates aluminum toxicity and regulates cadmium accumulation by spinach in strongly acidic soils.

Al toxicity and Cd pollution are key limiting factors for agricultural production in the acidic soils in China. The application of amendments is an effective and promising measure for remediating strongly acidic Cd-contaminated soils. However, the information on applying amendments for alleviating Al toxicity and regulating plant Cd accumulation is still rare. Here, oyster shell (OS), red mud (RM), hydroxyapatite (HAP), and biochar (BC) at 30 g kg-1 were investigated for alleviating Al toxicity and decreasing Cd accumulation in spinach plants. The results showed that four amendments significantly increased soil pH, and reduced soil exchangeable Al3+ and DTPA-Cd, promoted spinach growth (P < 0.05). Al(OH)30 and Al-HA were the main forms of active Al in soil. The BC and OS were more effective to alleviate Al toxicity but significantly (P < 0.05) increased Cd accumulation in spinach. RM and HAP effectively reduced the uptake of Cd by spinach plants as well as alleviated Al toxicity (P < 0.05). Bivariate correlation analysis and the partial least squares path modeling analysis indicated that soil exchangeable Al3+ was the main limiting factor for biomass production. Our study demonstrated that HAP could significantly alleviate Al toxicity, promote spinach growth, and decrease Cd accumulation in strongly acidic Cd-contaminated soils. Besides, OS and BC effectively alleviated soil Al toxicity leading to promoting the growth of spinach. Compared with CK, RM treatment significantly reduced soil Cd bioavailability (61.2%) and decreased Cd concentration and uptake of spinach plants by 90.0% and 50.7%. These results indicated that RM could be used as an efficient amendment in Cd contaminated.

A meta-analysis to examine whether nitrification inhibitors work through selectively inhibiting ammonia-oxidizing bacteria.

Nitrification inhibitor (NI) is often claimed to be efficient in mitigating nitrogen (N) losses from agricultural production systems by slowing down nitrification. Increasing evidence suggests that ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB) have the genetic potential to produce nitrous oxide (N2O) and perform the first step of nitrification, but their contribution to N2O and nitrification remains unclear. Furthermore, both AOA and AOB are probably targets for NIs, but a quantitative synthesis is lacking to identify the "indicator microbe" as the best predictor of NI efficiency under different environmental conditions. In this present study, a meta-analysis to assess the response characteristics of AOB and AOA to NI application was conducted and the relationship between NI efficiency and the AOA and AOB amoA genes response under different conditions was evaluated. The dataset consisted of 48 papers (214 observations). This study showed that NIs on average reduced 58.1% of N2O emissions and increased 71.4% of soil NH 4 + concentrations, respectively. When 3, 4-dimethylpyrazole phosphate (DMPP) was applied with both organic and inorganic fertilizers in alkaline medium soils, it had higher efficacy of decreasing N2O emissions than in acidic soils. The abundance of AOB amoA genes was dramatically reduced by about 50% with NI application in most soil types. Decrease in N2O emissions with NI addition was significantly correlated with AOB changes (R 2 = 0.135, n = 110, P < 0.01) rather than changes in AOA, and there was an obvious correlation between the changes in NH 4 + concentration and AOB amoA gene abundance after NI application (R 2 = 0.037, n = 136, P = 0.014). The results indicated the principal role of AOB in nitrification, furthermore, AOB would be the best predictor of NI efficiency.

Microstructural and histomorphological features of osteophytes in late-stage human knee osteoarthritis with varus deformity.

OBJECTIVES: To illustrate the microstructural and histomorphological characteristics of osteophytes in the human knee osteoarthritis (OA). METHODS: Tibial plateau specimens, including osteophytes and subchondral trabecular bone (STB) from weight-bearing and non-weight-bearing regions, were obtained from 81 patients with OA after total knee arthroplasty surgery. All the patients had varus deformity of the knee. Micro-CT was applied to evaluate the microstructure characteristics of the tibial plateau, which was segmented into 6 regions of interest (ROIs). After micro-CT scanning, decalcified and undecalcified bone histology were performed to assess histological features and bone remodeling status in these different ROIs. RESULTS: In both medial and lateral plateaus, osteophytes exhibited a less sclerotic microstructure and higher bone remodeling level compared with STB from weight-bearing and non-weight-bearing regions. Moreover, the medial osteophyte tended to have a more sclerotic microarchitecture and a relatively low level of bone metabolism than its lateral counterpart. Osteophyte, which consists of mesenchymal connective tissue cap, cartilage and mineralized bone tissue, demonstrated evident chondrocyte hypertrophy and endochondral ossification in the cartilage-to-bone interface. Compared with the non-weight-bearing region, the weight-bearing region showed more severely deteriorated cartilage, and more sclerotic subchondral bone with high remodeling status. CONCLUSION: Osteophytes exhibited a sparse microstructure and high bone remodeling level in knee OA, but demonstrating region-dependent variations. In addition, the microstructure, bone metabolism status and pathological alterations of osteochondral complex were distinct between weight-bearing and non-weight-bearing regions in the tibial plateau. Biomechanical stress might play a pivotal role in osteophyte formation and deterioration of osteochondral complex.

Contribution of ferroptosis and GPX4's dual functions to osteoarthritis progression.

BACKGROUND: Osteoarthritis (OA) is the most common joint disease and is the leading cause of chronic disability among older people. Chondrocyte death and extracellular matrix (ECM) degradation was involved in OA pathogenesis. Ferroptosis was an iron-dependent cell death associated with peroxidation of lipids. Here, we proved that ferroptosis exists in OA and identified glutathione peroxidase 4 (GPX4) as an important regulator of OA. METHODS: Ferroptosis-related alterations were analyzed in human OA and undamaged cartilage. Expression of GPX4 was examined in 55 paired human OA samples. Ferrostatin-1 (Fer-1) and Deferoxamine (DFO) were used to treat OA, in vitro and in vivo. Alterations of GPX4-mediated signaling pathway were identified by RNA-seq analysis. AAV-Gpx4-shRNA were used to downregulate GPX4 expression in vivo. FINDINGS: Transcriptomic, biochemical, and microscopical analyses indicated that ferroptosis was closely associated with OA. Expression of GPX4 in the OA cartilage from 55 OA patients were significantly lower than undamaged cartilage. Fer-1 and DFO could protect OA in a necroptosis-independent manner, suggesting that ferroptosis exists in OA prog. Importantly, GPX4 downregulation could increase the sensitivity of chondrocytes to oxidative stress and aggravate ECM degradation through the MAPK/NFκB pathway. Furthermore, downregulation of GPX4 expression by AAV-Gpx4 shRNA aggravated OA in vivo. INTERPRETATION: Ferroptosis contributes to OA pathogenesis and GPX4 was the intersection of two mechanisms in regulating OA progression: ferroptosis and ECM degradation. FUNDING: This work was supported by the Projects of International Cooperation and Exchanges of National Natural Science Funding of China (Grant no. 81820108020), the National Key Research and Development Project of China (Grant no. 2018YFC1106300) and the Basic Science Program of Shanghai Jiao Tong University Affiliated Sixth People's Hospital (Grant no. ynms202102).

Nb2C MXene-Functionalized Scaffolds Enables Osteosarcoma Phototherapy and Angiogenesis/Osteogenesis of Bone Defects.

Early surgical resection and chemotherapy of bone cancer are commonly used in the treatment of bone tumor, but it is still highly challenging to prevent recurrence and fill the bone defect caused by the resection site. In this work, we report a rational integration of photonic-responsive two-dimensional (2D) ultrathin niobium carbide (Nb2C) MXene nanosheets (NSs) into the 3D-printed bone-mimetic scaffolds (NBGS) for osteosarcoma treatment. The integrated 2D Nb2C-MXene NSs feature specific photonic response in the second near-infrared (NIR-II) biowindow with high tissue-penetrating depth, making it highly efficient in killing bone cancer cells. Importantly, Nb-based species released by the biodegradation of Nb2C MXene can obviously promote the neogenesis and migration of blood vessels in the defect site, which can transport more oxygen, vitamins and energy around the bone defect for the reparative process, and gather more immune cells around the defect site to accelerate the degradation of NBGS. The degradation of NBGS provides sufficient space for the bone remodeling. Besides, calcium and phosphate released during the degradation of the scaffold can promote the mineralization of new bone tissue. The intrinsic multifunctionality of killing bone tumor cell and promoting angiogenesis and bone regeneration makes the engineered Nb2C MXene-integrated composite scaffolds a distinctive implanting biomaterial on the efficient treatment of bone tumor.

A multifunctional substance P-conjugated chitosan hydrochloride hydrogel accelerates full-thickness wound healing by enhancing synchronized vascularization, extracellular matrix deposition, and nerve regeneration.

Due to the native skin limitations and the complexity of reconstructive microsurgery, advanced biomaterials are urgently required to promote wound healing for severe skin defects caused by accidents and disasters. Accumulating evidence has supported that substance P (SP) has a potential effect on skin regeneration. However, SP application is seriously impeded by its poor stability and oxidative reactions occurring during production, transportation, and storage. An SP-conjugated chitosan hydrochloride hydrogel (CSCl-SP) fabricated in this study demonstrated an enhanced capacity to repair full-thickness skin defects. CSCl-SP provided a stable in vitro delivery system for SP. The dissolution of CSCl-SP promoted the proliferation, migration, and tube formation, as well as angiogenesis-related gene and protein expression in human umbilical vein endothelial cells. CSCI-SP also stimulated the proliferation, migration, and production of anabolic growth factor in human fibroblasts. Moreover, CSCl-SP significantly promoted the neurite outgrowth in Neuro-2A cells. In vivo, CSCl-SP dramatically strengthened the vascularization, extracellular matrix deposition and remodeling, and nerve regeneration, thereby promoting efficient recovery of the full-thickness skin defect. Thus, synchronized multifunction of the CSCl-SP hydrogel makes it a promising and smart material for intractable skin defects.

miR-4286 functions in osteogenesis and angiogenesis via targeting histone deacetylase 3 and alleviates alcohol-induced bone loss in mice.

OBJECTIVES: Alcohol consumption is one of the leading factors contributing to premature osteopenia. MicroRNA (miRNA) coordinates a cascade of anabolic and catabolic processes in bone homeostasis and dynamic vascularization. The aim was to investigate the protective role of miR-4286 in alcohol-induced bone loss and its mechanism. MATERIALS AND METHODS: The effect of miR-4286 and alcohol on bone mesenchymal stem cells (BMSCs) and human umbilical vein endothelial cells (HUVECs) was explored via multiple in vitro assays, including cell proliferation, QPCR, Western blot, osteogenesis, angiogenesis etc miR-4286 directly regulated HDAC3 was investigated by luciferase reporter assay, and the function of HDAC3 was also explored in vitro. Moreover, alcohol-induced bone loss in mice was established to reveal the preventive effect of miR-4286 by radiographical and histopathological assays. RESULTS: In vitro, ethanol dramatically inhibited the proliferation and osteogenesis of BMSCs, and substantially impaired the proliferation and vasculogenesis of HUVECs. However, a forced overexpression of miR-4286 within BMSCs and HUVECs could largely abolish inhibitory effects by alcohol. Furthermore, alcohol-induced inhibition on osteogenic and vasculogenic functions was mediated by histone deacetylase 3 (HDAC3), and dual-luciferase reporter assay showed that HDAC3 was the direct binding target of miR-4286. In vivo, micro-CT scanning and histology assessment revealed that miR-4286 could prevent alcohol-induced bone loss. CONCLUSIONS: We firstly demonstrated that miR-4286 might function via intimate osteogenesis-angiogenesis pathway to alleviate alcohol-induced osteopenia via targeting HDAC3.

Intercellular mitochondrial transfer as a means of tissue revitalization.

As the crucial powerhouse for cell metabolism and tissue survival, the mitochondrion frequently undergoes morphological or positional changes when responding to various stresses and energy demands. In addition to intracellular changes, mitochondria can also be transferred intercellularly. Besides restoring stressed cells and damaged tissues due to mitochondrial dysfunction, the intercellular mitochondrial transfer also occurs under physiological conditions. In this review, the phenomenon of mitochondrial transfer is described according to its function under both physiological and pathological conditions, including tissue homeostasis, damaged tissue repair, tumor progression, and immunoregulation. Then, the mechanisms that contribute to this process are summarized, such as the trigger factors and transfer routes. Furthermore, various perspectives are explored to better understand the mysteries of cell-cell mitochondrial trafficking. In addition, potential therapeutic strategies for mitochondria-targeted application to rescue tissue damage and degeneration, as well as the inhibition of tumor progression, are discussed.

Chrysophanic acid shifts the differentiation tendency of BMSCs to prevent alcohol-induced osteonecrosis of the femoral head.

OBJECTIVES: Osteonecrosis of the femoral head (ONFH), largely caused by alcohol abuse, is a refractory bone disease characterized by the impaired capacity of osteogenic differentiation of bone mesenchymal stem cells (BMSCs), as well as the disordered adipocyte accumulation. Chrysophanic acid (CPA) is a natural anthraquinone which has lipid regulation and bone protection capacity. The aim of this study was to reveal the potential function of CPA and the underlying mechanisms for the alcohol-induced ONFH. MATERIALS AND METHODS: The effects of alcohol and CPA on BMSCs were investigated by cell proliferation, induced differentiation assays and immunofluorescent staining. Meanwhile, the function of PI3K/AKT and AMPK pathway was investigated in the process of osteogenic and adipogenic differentiation, respectively. Furthermore, we established the rat model of alcohol-induced ONFH to reveal the pharmacotherapeutic effect of CPA in vivo using radiographical and histopathological methods. RESULTS: In vitro, alcohol significantly inhibited the proliferation and osteogenic differentiation of BMSCs but stimulated the adipogenic differentiation. However, CPA could counteract the anti-osteogenesis of alcohol partly via PI3K/AKT pathway and retard the promotion of alcohol-induced adipogenesis via AMPK pathway. In vivo, radiographical and histopathological findings showed that CPA could alleviate alcohol-induced ONFH and substantially restore the bone volume. CONCLUSIONS: We demonstrated that CPA ameliorated alcohol-induced ONFH possibly via regulating the differentiation tendency of BMSCs. Hence, CPA may become a beneficial herb extract to alleviate alcohol-induced ONFH.

miR-136-3p targets PTEN to regulate vascularization and bone formation and ameliorates alcohol-induced osteopenia.

Alcohol consumption is regarded as one of the leading risk factors for secondary osteopenia. Coupled angiogenesis and osteogenesis via distinct type-H vessels orchestrates subtle biological processes of bone homeostasis. The dysfunction of angiogenesis and osteogenesis contributes to decreased bone mass during the development of osteopenia. Herein, we identified microRNA-136-3p was remarkedly downregulated in the mouse model of alcohol-induced osteopenia. Following the alcohol administration, downregulated microRNA-136-3p significantly suppressed vascularization and osteogenic differentiation in human umbilical vein endothelial cells (HUVECs) and bone mesenchymal stem cells (BMSCs), respectively. Furthermore, microRNA-136-3p could target phosphatase and tensin homolog deleted on chromosome ten (PTEN) in both HUVECs and BMSCs, thus substantially modulating the capacity of vessel formation and osteogenic differentiation. In the mouse model, microRNA-136-3p Agomir ameliorated alcohol-induced osteopenia, with the concomitant restoration of bone mass and type-H vessel formation. For the first time, this study demonstrated the pivotal role of microRNA-136-3p/PTEN axis in regulations of vascularization and bone formation, which might become the potential therapeutic target of alcohol-induced bone loss.

Engineering 2D Mesoporous Silica@MXene-Integrated 3D-Printing Scaffolds for Combinatory Osteosarcoma Therapy and NO-Augmented Bone Regeneration.

The rising concerns of the recurrence and bone deficiency in surgical treatment of malignant bone tumors have raised an urgent need of the advance of multifunctional therapeutic platforms for efficient tumor therapy and bone regeneration. Herein, the construction of a multifunctional biomaterial system is reported by the integration of 2D Nb2 C MXene wrapped with S-nitrosothiol (RSNO)-grafted mesoporous silica with 3D-printing bioactive glass (BG) scaffolds (MBS). The near infrared (NIR)-triggered photonic hyperthermia of MXene in the NIR-II biowindow and precisely controlled nitric oxide (NO) release are coordinated for multitarget ablation of bone tumors to enhance localized osteosarcoma treatment. The in situ formed phosphorus and calcium components degraded from BG scaffold promote bone-regeneration bioactivity, augmented by sufficient blood supply triggered by on-demand NO release. The tunable NO generation plays a crucial role in sequential adjuvant tumor ablation, combinatory promotion of coupled vascularization, and bone regeneration. This study demonstrates a combinatory osteosarcoma ablation and a full osseous regeneration as enabled by the implantation of MBS. The design of multifunctional scaffolds with the specific features of controllable NO release, highly efficient photothermal conversion, and stimulatory bone regeneration provides an intriguing biomaterial platform for the diversified treatment of bone tumors.