Targeting signaling pathways in osteosarcoma: Mechanisms and clinical studies.

Osteosarcoma (OS) is a highly prevalent bone malignancy among adolescents, accounting for 40% of all primary malignant bone tumors. Neoadjuvant chemotherapy combined with limb-preserving surgery has effectively reduced patient disability and mortality, but pulmonary metastases and OS cells' resistance to chemotherapeutic agents are pressing challenges in the clinical management of OS. There has been an urgent need to identify new biomarkers for OS to develop specific targeted therapies. Recently, the continued advancements in genomic analysis have contributed to the identification of clinically significant molecular biomarkers for diagnosing OS, acting as therapeutic targets, and predicting prognosis. Additionally, the contemporary molecular classifications have revealed that the signaling pathways, including Wnt/ß-catenin, PI3K/AKT/mTOR, JAK/STAT3, Hippo, Notch, PD-1/PD-L1, MAPK, and NF-κB, have an integral role in OS onset, progression, metastasis, and treatment response. These molecular classifications and biological markers have created new avenues for more accurate OS diagnosis and relevant treatment. We herein present a review of the recent findings for the modulatory role of signaling pathways as possible biological markers and treatment targets for OS. This review also discusses current OS therapeutic approaches, including signaling pathway-based therapies developed over the past decade. Additionally, the review covers the signaling targets involved in the curative effects of traditional Chinese medicines in the context of expression regulation of relevant genes and proteins through the signaling pathways to inhibit OS cell growth. These findings are expected to provide directions for integrating genomic, molecular, and clinical profiles to enhance OS diagnosis and treatment.

Supplementation of hyaluronic acid injections with vitamin D improve knee function by attenuating synovial fluid oxidative stress in osteoarthritis patients with vitamin D insufficiency.

Objectives: There is still controversy about the effect of vitamin D supplementation on osteoarthritis (OA). The purpose of this study was to investigate the effects of vitamin D supplementation with Hyaluronic acid (HA) injection on OA. Methods: We investigated serum vitamin D levels and oxidative stress (OS) in synovial fluid from patients with OA who underwent total knee arthroplasty (grade IV, n = 24) and HA injection (grade II and III, n = 40). The effects of HA injection with or without oral vitamin D supplementation on synovial fluid OS and knee pain and function were then further investigated. Finally, patients underwent HA injection were divided into two groups according to vitamin D levels (vitamin D < or > 30 ng/ml), and the efficacy of the two groups were compared. Results: The results showed that the levels of glutathione peroxidase (GSH-PX) (P < 0.05) in the synovial fluid were lower in patients with stage IV OA than that in patients with stage II-III OA, while the levels of malondialdehyde (MDA) (P < 0.05) and lactate dehydrogenase (LDH) (P < 0.01) were significantly higher. Moreover, we found that age, BMI and vitamin D levels were significantly associated with the levels of oxidants and/or antioxidants in synovial fluid, and that vitamin D was significantly negatively correlated with BMI (R = -0.3527, p = 0.0043). Supplementation of HA injections with vitamin D significantly reduced the OS status in synovial fluid, attenuated knee pain and improved knee function in OA patients with vitamin D insufficiency. Conclusion: We conclude that maintenance of vitamin D sufficiency may be beneficial for the treatment of OA by improving OS in synovial fluid.

Phytochemicals, biological activity, and industrial application of lotus seedpod (Receptaculum Nelumbinis): A review.

Lotus (Nelumbo nucifera Gaertn.) is a well-known food and medicinal plant. Lotus seedpod (Receptaculum Nelumbinis) is the by-products during lotus products processing, which is considered as waste. Numerous studies have been conducted on its phytochemicals, biological activity and industrial application. However, the information on lotus seedpod is scattered and has been rarely summarized. In this review, summaries on preparation and identification of phytochemicals, the biological activities of extracts and phytochemicals, and applications of raw material, extracts and phytochemicals for lotus seedpod were made. Meanwhile, the future study trend was proposed. Recent evidence indicated that lotus seedpods extracts, obtained by non-organic and organic solvents, possessed several activities, which were influenced by extraction solvents and methods. Lotus seedpods were rich in phytochemicals categorized as different chemical groups, such as proanthocyanidins, oligomeric procyanidins, flavonoids, alkaloids, terpenoids, etc. These phytochemicals exhibited various bioactivities, including ameliorating cognitive impairment, antioxidation, antibacterial, anti-glycative, neuroprotection, anti-tyrosinase and other activities. Raw material, extracts and phytochemicals of lotus seedpods could be utilized as sources for biochar and biomass material, in food industry and as dye. This review gives well-understanding on lotus seedpod, and provides theoretical basis for its future research and application.

Influence path identification of topography, soil, hydrology and landscape on phosphorus buffering capacity in typical agricultural catchments in central subtropical China.

The catchment phosphorus buffering capacity (PBF) determines the pressure-state-response relationship between anthropogenic P inputs and aquatic ecosystems at a catchment scale, and is affected by biogeochemical, hydrological, and ecological catchment characteristics. However, the complex relationship between these catchment characteristic factors and their impact pathways on PBF remains ambiguous, leading to large uncertainty in balancing agricultural productivity and water conservation via improving BF through management practices. In this study, the short-term buffering index, calculated from net anthropogenic P input and riverine P exports, was used to quantify the spatiotemporal variations in PBF in source agricultural catchments in the Dongting Lake basin. Partial least squares structural equation modeling was used to investigate the relationship between the PBF and the catchment characteristics. The results indicate that catchment PBF was directly determined by soil properties and hydrological conditions, while landscape patterns significantly mediated the effects of topography on soil and hydrology. Considering the pathway preferences of the model, landscape patterns could be the priority for characterizing and regulating PBF. According to a change-point analysis, the probability of PBF weakening increases dramatically when the proportion of farmland (Farm%) > 24.6%, degree of patch interspersion (Contagion index) < 64.5%, and Perimeter-Area Ratio Distribution (PARA) > 348.7. These findings provide new insights into catchment buffering mechanisms and can be used to promote the simultaneous achievement of agricultural production and environmental conservation goals.

Landscape patterns of catchment and land-use regulate legacy phosphorus releases in subtropical mixed agricultural and woodland catchments.

Landscape composition and configuration determine the exchange of matter and energy among different landscape patches and may affect riverine phosphorus (P) exports derived from watershed legacy sources. However, a lack of understanding of landscape pattern effects on legacy P releases has yielded large uncertainties in mitigating watershed water quality using management practices or landscape planning. This study revealed the significance of legacy effect in the headwater catchments through the time-lag response of the long-term trend of river P exports to the change of net anthropogenic P input (NAPI). By constructing empirical statistical models that incorporated NAPI, hydroclimatic, terrain factors, soil chemical properties, and land use variables, the sources of annual riverine total phosphorus (TP) and dissolved inorganic phosphorus (DIP) exports were divided into current annual NAPI input and legacy sources inputs. The model estimations indicated that the contribution of legacy sources to riverine TP exports was 0.33-1.12 kg ha-1 yr-1 (50.7-82.8%), which was significantly higher than the contribution to DIP exports (0.18-0.49 kg ha-1 yr-1, 42.4-81.4%) in 2012-2017. Redundancy analysis (RDA) and variance partitioning analysis (VPA) methods were used to quantify the relative contribution of landscape patterns, soil P content, and terrain factors to legacy P releases. Results revealed that the relative contribution of the landscape composition and configuration to the total variations of legacy P releases was greater than that of the soil P and terrain factors. For different land use patches, a large area of woodland with a high aggregation degree and a large area of ponds with multiple net structures may significantly alleviate legacy P releases. In contrast, the legacy P releases were significantly positively associated with highly aggregated agricultural, tea plantation, and residential patches. This study provides theoretical support for strategies aiming to control legacy P from the perspective of landscape planning.

Flooding and straw returning regulates the partitioning of soil phosphorus fractions and phoD-harboring bacterial community in paddy soils.

Flooding and straw returning are effective agricultural practices in promoting phosphorus (P) availability in paddy soils. However, little is known about the effects of these practices and their interaction on the soil P pools and functional microbes responsible for soil P mobilization. Our 4-year paddy field experiment aimed to analyze the responses of soil P fractions and phoD-harboring bacterial communities in a double-rice cropping system to intermittent flooding (IF) and continuous flooding (CF), in plots with (+ S) and without (-S) straw return. Compared to IF, CF significantly increased soil citrate-P and marginally decreased the HCl-P fractions, suggesting that the stable inorganic P pools are transferred to labile inorganic P at lower redox potentials. Compared to the -S treatments, + S treatments significantly increased the labile organic fractions (enzyme-P). Correspondingly, a decreased soil total organic P concentration was observed in + S treatment. Additionally, + S treatment significantly increased the activity of acid phosphomonoesterase and alkaline phosphomonoesterase and the abundance of phoD-harboring bacteria. These results indicated that straw promoted organic P minimization to release orthophosphate. The diversity of the phoD-harboring bacteria and complexity of the co-occurrence network decreased under the CF + S treatment; however, all keystone species of the phoD-harboring bacteria were retained in this oxygen-deficient environment. This study highlights that irrigation regimes mediate the processes of inorganic P mobilization, while straw returns regulate the processes of organic P mineralization. Additionally, flooding could be a more effective agricultural practice than straw returning to promote soil P availability in paddy soils. KEY POINTS: •Soil P pools and phoD-harboring bacteria communities were assessed. •Straw return mainly affects the mineralization of organic P. •Continuous flooding mainly affects the mobilization of inorganic P.

Pathways and mechanisms by which biochar application reduces nitrogen and phosphorus runoff losses from a rice agroecosystem.

Biochar application has the potential to reduce nitrogen (N) and phosphorus (P) losses in agricultural runoff, but little is known about how and to what extent biochar is effective in rice agroecosystems. In this study, in a typical double-rice cropping system, N and P runoff losses and soil carbon (C), N, and P contents (soil CNP contents) were observed under three different biochar application rates (0, 24, and 48 t ha-1, which were defined as CK, LB, and HB, respectively) from 2017 to 2019. The results showed that the two-year averages of soil total organic C (TOC), total N (TSN), total P (TSP), available P (Olsen P), microbial biomass N (MBN), and microbial biomass P (MBP) contents were generally higher in the biochar treatments than in CK (P < 0.05). Specifically, the TSP, TOC, and MBN contents increased with the increasing biochar application rate, thus demonstrating the significant effects of biochar application on the paddy soil CNP contents and composition. The HB and LB treatments reduced the seasonal mean runoff flow-weighted total N (TN_wc) and total P (TP_wc) concentrations by 32.4% and 42.1%, respectively, compared to CK. Structural equation modeling (SEM) further revealed that the paths and mechanisms by which biochar reduced the TN_wc and TP_wc were different, depending on the different application rates. HB reduced the TN_wc mainly through the direct absorption of N, followed by the indirect inhibition of N mineralization, whereas LB decreased the TP_wc mainly through the strong P sorption capacity of the biochar. The direct effect of HB on the TN_wc was 1.58 times as strong as the indirect effect (path coefficients: -0.68 vs. 0.43, respectively), and the direct effect of LB on the TP_wc was 1.78 times as strong as the indirect effect (path coefficients: -0.89 vs. 0.50, respectively). Given the distinct pathways and mechanisms by which biochar reduced NP runoff losses, in practice, the biochar application rate should be optimized according to a targeted priority of reducing either N or P runoff losses in rice agroecosystems.

Nitrogen and phosphorus runoff losses were influenced by chemical fertilization but not by pesticide application in a double rice-cropping system in the subtropical hilly region of China.

As one of the important nitrogen (N) and phosphorus (P) pollution sources of waters, the paddy water N and P runoff losses are still poorly understood in the double rice cropping system under the interaction of chemical fertilizer and pesticide. In the subtropical hilly region of China, we conducted a 1.5-year continuous and high-frequency monitoring of paddy water N and P concentrations, runoff N and P losses, and grain yield in a double rice-cropping system with different chemical fertilizer and pesticide application rates. The results showed that the high-risk periods for N loss were in the first 5 days after the base fertilizer (BF) application and the first 10 days after the topdressing fertilizer application in both early and late rice seasons, while the high-risk periods for P loss were in the first 5 days after BF application in the early rice season and the first 15 days after BF application in the late rice season. The N and P runoff losses in the early rice season were greater than those in the late rice season, due to that the N and P fertilizers use efficiencies were lower, and thus paddy water N and P concentrations were higher in the early rice season. The paddy N and P concentrations and N and P runoff losses increased significantly with increased fertilizer application rates, while the pesticide application rate did not significantly affect N and P losses. Therefore, special effects (e.g., avoiding high irrigation, fertilizer deep application) should be taken during the high-risk periods of N and P losses to reduce the N and P runoff losses in the double rice cropping system, especially in the early rice season. There are also potentials to reduce fertilizer and pesticide input without reducing rice grain yield for the double rice cropping system in the subtropical hilly region of China.

Dynamics and underlying mechanisms of N2O and NO emissions in response to a transient land-use conversion of Masson pine forest to tea field.

Nowadays, there has been a rapid expansion of tea field converted from forestry for pursuing higher economic benefits. However, few researches focus on the effects of transient land-use conversion from Masson pine forest to artificial tea fields on soil N2O and NO emissions and the underlying mechanisms. A parallel field experiment was conducted from Masson pine forest and a newly converted tea plantation from Masson pine forest from 2013 to 2017 in subtropical central China. Masson pine forest conversion to tea field dramatically increased soil N2O and NO emissions (up to 4.00 ±â€¯0.43 and 1.93 ±â€¯0.45 kg N ha-1 yr-1, respectively) in the first year possibly due to enhanced soil organic N mineralization. With the extension of tea planting age, N2O and NO emissions showed an upward trend (ranged from 1.19 to 5.28, and 0.15 to 1.78 kg N ha-1 yr-1, respectively) influenced by fertilization and soil organic matter accumulation. The direct emission factors for N2O and NO in the newly converted tea fields were the largest in the first year (2.64 and 1.07%, respectively) after land-use conversion, and higher than the default value recommended by IPCC. The NO/N2O ratio was mainly lower than 1 in the fertilized tea field, and soil N2O and NO emission peaks mainly occurred in tea-growing season (wet season) with higher soil moisture and NH4+-N concentrations, and dominated by amoA-containing bacteria (AOB), suggesting nitrifier-denitrification could be the dominant process involved in soil nitrogenous gases emissions in tea field. These results can be summarized as dramatically increased soil N2O and NO emissions during the transient land-use conversion from Masson pine forest to tea field were possibly due to the substantial net soil organic N mineralization and the enhanced abundance of nitrification functional genes (AOB).

Mitochondrial Pyruvate Carriers Prevent Cadmium Toxicity by Sustaining the TCA Cycle and Glutathione Synthesis.

Cadmium (Cd) is a major heavy metal pollutant, and Cd toxicity is a serious cause of abiotic stress in the environment. Plants protect themselves against Cd stress through a variety of pathways. In a recent study, we found that mitochondrial pyruvate carriers (MPCs) are involved in Cd tolerance in Arabidopsis (Arabidopsis thaliana). Following the identification of MPCs in yeast (Saccharomyces cerevisiae) in 2012, most studies have focused on the function of MPCs in animals, as a possible approach to reduce the risk of cancer developing. The results of this study show that AtMPC protein complexes are required for Cd tolerance and prevention of Cd accumulation in Arabidopsis. AtMPC complexes are composed of two elements, AtMPC1 and AtMPC2 (AtNRGA1 or AtMPC3). When the formation of AtMPCs was interrupted by the loss of AtMPC1, glutamate could supplement the synthesis of acetyl-coenzyme A and sustain the TCA cycle. With the up-regulation of glutathione synthesis following exposure to Cd stress, the supplementary pathway could not efficiently drive the tricarboxylic acid cycle without AtMPC. The ATP content decreased concomitantly with the deletion of tricarboxylic acid activity, which led to Cd accumulation in Arabidopsis. More importantly, ScMPCs were also required for Cd tolerance in yeast. Our results suggest that the mechanism of Cd tolerance may be similar in other species.

Effect of controlled-release fertilizer on N2O emissions and tea yield from a tea field in subtropical central China.

Tea (Camellia sinensis L.), a perennial leaf-harvested crop, favors warm/humid climate and acidic/well-drained soils, and demands high nitrogen (N) fertilizer inputs which lead to significant emissions of N2O. Potential mitigation options should be adopted to improve N use efficiency (NUE) and reduce environmental pollution in tea field system. A 3-year field experiment was carried out in a tea field in southern China from January 2014 to December 2016 to investigate the effect of controlled-release fertilizer (CRF) application on N2O emissions in tea field system. Three practices, namely conventional treatment (CON, 105 kg N-oilcake ha-1 year-1 + 345 kg N-urea ha-1 year-1), treatment with a half amount of the N fertilizer (CRF50%, 105 kg N-oilcake ha-1 year-1 + 120 kg N CRF ha-1 year-1) and full amount of N fertilizer (CRF100%, 105 kg N-oilcake ha-1 year-1 + 345 kg N CRF ha-1 year-1) were used. Compared with the CON, our results showed that CRF50% reduced the N2O emissions by 26.2% (p > 0.05) and increased the tea yield by 31.3% (p > 0.05), while CRF100% significantly increased the N2O emissions by 96.7% (p < 0.05) and decreased the tea yield by 6.77% (p > 0.05). Overall, yield-scaled N2O emissions of tea were reduced by 44.5% (p > 0.05) under CRF50% and significantly increased by 100% (p < 0.05) under CRF100%, compared with CON. Based on the gross margin analysis, CRF50% obtained the highest net economic profit. Our findings suggest that reducing N input of CRF (CRF50%) is necessary and feasible for adoption in the current tea plantation system.