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Abstract Biochar and organic fertilizer substitution have been utilized to improve crop yields and promote sustainable agricultural development. However, few studies have focused on how biochar and organic fertilizer substitution regulate the diversities of bacterial meta-communities and sub-communities (i.e., habitat specialists and generalists) within soil aggregates on the Loess Plateau. A field experiment, containing six treatments, namely no fertilizer (CK), no fertilizer plus 104 kg ha−1 biochar (CK + B), traditional N fertilizer (TF, 150 kg N ha−1), traditional N fertilizer plus 104 kg ha−1 biochar (TF + B), organic fertilizer replacing (OF), and organic fertilizer replacing plus 104 kg ha−1 biochar (OF + B), was adopted to explore the influences of biochar and organic fertilizer substitution on the size distribution, nutrient levels, extracellular enzymatic stoichiometry, bacterial meta-community and sub-community diversities, structures, ecological networks, and assembly processes within bulk soil, large macro-aggregates (> 2 mm), small macro-aggregates (0.25–2 mm), and micro-aggregates (

Global warming can cause surface temperatures to rise, which can trigger permafrost degradation and severe soil erosion. This erosion can contribute to the degradation of water and soil resources and threaten the stability of the terrestrial ecosystem of the cryosphere, which can also contribute to geological tectonic changes in cold regions. However, there is limited research on the changes in horizontal settlement that occurs during permafrost thawing. To study the internal settlement of permafrost after thawing, four types of soilice mixtures were thawed and analysed indoors to quantitatively describe the internal settlement process and moisture conditions in thawing permafrost and to determine the variation in permafrost thawing and settlement processes. The results indicated that there were variations in the packing density of the soil–ice mixtures according to the soil type. Additionally, the packing density exhibited a favourable correlation with the water content, and the following size relationship for the packing density of the different soil types at the same water content could be established: ST (sand) > HB (silty loam) > SL (sandy loam) > YC (silty clay). The soil types exhibited varying surface soil coefficients of variation (Cv), with sample HB yielding the highest Cv value of 10.15 % and sample SL exhibiting the lowest Cv value of 5.85 %. Cv gradually decreased with increasing sample depth, and the Cv in the deepest horizon reached approximately 1.58 %. There was a significant difference in the amount of surface settlement in the vertical direction among the different samples (P 0.05). The residual thickness of the soil horizon in the samples tended to decrease with increasing soil horizon depth. In this study, the settlement deformation of the soil horizon in the freeze–thaw process along the horizontal and vertical directions was examined, which could provide a reference for the regulation of the evolution of the geological structure during permafrost degradation and theoretical guidance for studying engineering instability in cold regions.

Due to the existence of an electric double layer in the soil, frozen soil always has a certain amount of unfrozen water. And it will migrate under the action of the electric field. Select a kind of frost heave-sensitive soil (Lanzhou loess) as the object of study, and several bench-scale experiments on frozen Lanzhou loess were performed using 4, 6, 8, 10, and 12 V/cm potential gradients. The water content was measured after tests to investigate the relationship between water migration and applied potential gradient. The current was monitored during the experiments to calculate the energy consumption, and to evaluate the usability of electroosmosis in the frozen soil. The amount of water migration increase with the increase of potential gradient and the varied water content with potential gradients can be divided into steady, fluctuation, and incremental stage. The variation of current can reflect the process of water migration to a certain extent and can be divided into two stages, and water migration mainly occurs at the stage of drastic change of current.

In the northern Da Xing’anling Mountains in Northeast China on the southern margin of the Eastern Asia permafrost body, the ground thermal state and boreal ecological environment are sensitive to climate change and human activities. Since the 1980s, the Hola Basin here has been continuously and extensively developed. In particular, open pits and later backfilling in strip coal mining alters land–atmospheric hydrothermal exchanges in permafrost regions, leading to serious damages to the permafrost environment and boreal forest. After mining, pits need to be backfilled timely and properly for hydrothermal recovery of Xing’an permafrost and the boreal ecological environment. In this study, based on the comparative analysis of monitored ground temperatures in backfilled and undisturbed areas, influencing factors of thermal recovery after backfilling were analyzed through numerical simulations. Results show that the thermal recovery of permafrost in the backfilled area is closely related to temperature, depth, material, and soil moisture content of backfill. The warmer, finer, and thicker the backfill soils, the longer the permafrost recovery. Thermal recovery of permafrost also depends on the moisture content of backfill; the shortest recovery occurs at 15–25% in the backfilled soil moisture content. Based on numerical simulations and combined with enlightenments from features of the ecosystem-protected Xing’an permafrost in Northeast China, a composite configuration of organic soil, crush-rock layer, and proper re-vegetation measures is advised. Based on prudent regulation of heat transfer modes, this composite backfilling method can effectively cool the backfilled ground and can even possibly offset the climate warming.

The cone-cylindrical pile foundation is a kind of shallow buried foundation, which needs to be open excavated and backfilled during construction. The density of the backfill is closely related to the refreezing process of the backfill. However, there is still a lack of relevant research on the relationship between backfill density and the refreezing process of backfill. The method of model experiment is selected to study the refreezing process of backfill under three backfill soil densities. The controlled density of backfill is 1.83, 1.62 and 1.36 g/cm3, and the times of freeze–thaw cycle is 14, 22 and 39, respectively. The main research findings are as follows: First, the effect of the initial temperature of the backfill on the refreezing is mainly reflected in the first three freeze–thaw cycles; the second is that the higher the density of the backfill, the faster the backfill responds to changes in outside air temperature, and the shorter the freezing time; third, the pile foundation is a good conductor of heat, which will cause the soil temperature change on the pile side to be significantly greater than that of the natural soil, and the temperature change of the pile foundation surface is greater than that of the backfill. The research results can provide a reference for the backfill construction of pile foundations in cold regions and the selection of boundary conditions for related numerical simulations.

Osteosarcoma is the most common primary malignancy of bones and primarily occurs in adolescents and young adults. However, a second smaller peak of osteosarcoma incidence was reported in the elderly aged more than 60. Elderly patients with osteosarcoma exhibit different characteristics compared to young patients, which usually results in a poor prognosis. The mechanism underlying osteosarcoma development in elderly patients is intriguing and of significant value in clinical applications. Senescent cells can accelerate tumor progression by metabolic reprogramming. Recent research has shown that methylmalonic acid (MMA) was significantly up-regulated in the serum of older individuals and played a central role in the development of aggressive characteristics. We found that the significant accumulation of MMA in elderly patients imparted proliferative potential to osteosarcoma cells. The expression of MAFB was excessively up-regulated in osteosarcoma specimens and was further enhanced in response to MMA accumulation as the patient aged. Specifically, we first confirmed a novel molecular mechanism between cellular senescence and cancer, in which the MMA-driven transcriptional reprogramming of the MAFB-NOTCH3 axis accelerated osteosarcoma progression via the activation of PI3K-AKT pathways. Moreover, the down-regulation of the MAFB-NOTCH3 axis increased the sensitivity and effect of AKT inhibitors in osteosarcoma through significant inhibition of AKT phosphorylation. In conclusion, we confirmed that MAFB is a novel age-dependent biomarker for osteosarcoma, and targeting the MAFB-NOTCH3 axis in combination with AKT inhibition can serve as a novel therapeutic strategy for elderly patients with osteosarcoma in experimental and clinical trials.

The purpose of this paper is to study the influence of different adhesives and dosage on the performance of ink absorption coating and improve the quality of foam surface. In this experiment, silica was used as pigment, PVA1788, PVA1799, PVA235 and soluble starch were used as binders, and rigid polyurethane foam was used as coating object. In this experiment, a spraying method was used to coat the surface of plastic foam, UV printer was used for graphic output, and related equipment were used to test the performance of the coating. The results showed that when the ratio of adhesive (PVA1788) to pigment was 20%, the whiteness and wettability of the coating were the best. In this case, rich color range and gradation level could be obtained. With the increase of the alcoholysis of polyvinyl alcohol, the dissolution became difficult, water resistance increased, bonding force increased, film formation became better, and the contact angle of the coating prepared by the high alcoholysis of PVA as adhesive was lower. The coating with PVA235 as adhesive had the highest color density and the best comprehensive effect. [ABSTRACT FROM AUTHOR]

Abstract Background Osteosarcoma is a malignant bone tumor that usually affects adolescents aged 15–19 y. The DNA damage response (DDR) is significantly enhanced in osteosarcoma, impairing the effect of systemic chemotherapy. Targeting the DDR process was considered a feasible strategy benefitting osteosarcoma patients. However, the clinical application of DDR inhibitors is not impressive because of their side effects. Chinese herbal medicines with high anti-tumor effects and low toxicity in the human body have gradually gained attention. 2-Hydroxy-3-methylanthraquinone (HMA), a Chinese medicine monomer found in the extract of Oldenlandia diffusa, exerts significant inhibitory effects on various tumors. However, its anti-osteosarcoma effects and defined molecular mechanisms have not been reported. Methods After HMA treatment, the proliferation and metastasis capacity of osteosarcoma cells was detected by CCK-8, colony formation, transwell assays and Annexin V-fluorescein isothiocyanate/propidium iodide staining. RNA-sequence, plasmid infection, RNA interference, Western blotting and immunofluorescence assay were used to investigate the molecular mechanism and effects of HMA inhibiting osteosarcoma. Rescue assay and CHIP assay was used to further verified the relationship between MYC, CHK1 and RAD51. Results HMA regulate MYC to inhibit osteosarcoma proliferation and DNA damage repair through PI3K/AKT signaling pathway. The results of RNA-seq, IHC, Western boltting etc. showed relationship between MYC, CHK1 and RAD51. Rescue assay and CHIP assay further verified HMA can impair homologous recombination repair through the MYC-CHK1-RAD51 pathway. Conclusion HMA significantly inhibits osteosarcoma proliferation and homologous recombination repair through the MYC-CHK1-RAD51 pathway, which is mediated by the PI3K-AKT signaling pathway. This study investigated the exact mechanism of the anti-osteosarcoma effect of HMA and provided a potential feasible strategy for the clinical treatment of human osteosarcoma. Graphical Abstract

Abstract SGLT2 (sodium-glucose cotransporter 2) is an important mediator of epithelial glucose transport and has been reported that SGLT2, robustly and diffusely expressed in malignant cancer cells, was overexpressed in various tumors, and inhibiting the SGLT2 expression significantly inhibited tumor progression. By blocking the functional activity of SGLT2, SGLT2 inhibitors have shown anticancer effects in several malignant cancers, including breast cancer, cervical cancer, hepatocellular cancer, prostate cancer, and lung cancer. However, the anticancer effect of SGLT2 inhibitors in osteosarcoma and the specific mechanism are still unclear. In the present study, we found that SGLT2 was overexpressed at the protein level in osteosarcoma. Furthermore, our results showed that the SGLT2 inhibitor significantly inhibited osteosarcoma tumor growth and induced infiltration of immune cells in vivo by upregulating STING expression and activating the IRF3/IFN-β pathway, which could attribute to the suppression of AKT phosphorylation. In addition, the combined treatment with SGLT2 inhibitor and STING agonist 2’3’-cGAMP exerted synergistic antitumor effects in osteosarcoma. Furthermore, the overexpression of SGLT2 at the protein level was correlated with the degradation of SGLT2 induced by TRIM21. This result demonstrated that SGLT2 is a novel therapeutic target of osteosarcoma, and that the SGLT2 inhibitor, especially in combination with 2’3’-cGAMP, is a potential therapeutic drug.

Cancer-induced bone pain (CIBP) has a considerable impact on patients’ quality of life as well as physical and mental health. At present, patients with CIBP are managed according to the three-step analgesic therapy algorithm proposed by the World Health Organization. Opioids are commonly used as the first-line treatment for moderate-to-severe cancer pain but are limited due to addiction, nausea, vomiting and other gastrointestinal side effects. Moreover, opioids have a limited analgesic effect in some patients. In order to optimize the management of CIBP, we must first identify the underlying mechanisms. In some patients, surgery, or surgery combined with radiotherapy or radiofrequency ablation is the first step in the management of CIBP. Various clinical studies have shown that anti-nerve growth factor (NGF) antibodies, bisphosphonates, or RANKL inhibitors can reduce the incidence and improve the management of cancer pain. Herein, we review the mechanisms of cancer pain and potential therapeutic strategies to provide insights for optimizing the management of CIBP.

Osteosarcoma is the most common bone tumor affecting both adolescents and children. Although localized osteosarcoma has an overall survival of >70% in the clinic, metastatic, refractory, and recurrent osteosarcoma have poorer survival rates. Exosomes are extracellular vesicles released by cells and originally thought to be a way for cells to discard unwanted products. Currently, exosomes have been reported to be involved in intercellular cross-talk and induce changes in cellular behavior by transferring cargoes (proteins, DNA, RNA, and lipids) between cells. Exosomes regulate osteosarcoma progression, and processes such as tumorigenesis, proliferation, metastasis, angiogenesis, immune evasion, and drug resistance. Increasing evidences shows that exosomes have significant potential in promoting osteosarcoma progression and development. In this review, we describe the current research status of exosomes in osteosarcoma, focusing on the biological functions of osteosarcoma exosomes as well as their application in osteosarcoma as diagnostic biomarkers and therapeutic targets.

Abstract Background Recently, microRNA-20a (miR-20a) has been reported to influence the clinical features and may have prognostic value in human cancers. The present meta-analysis assessed the prognostic role of miR-20a in various carcinomas. Methods Literature searches of seven electronic databases were performed for eligible articles of the prognostic role of miR-20a in human cancers. Hazard ratios (HR) for overall survival (OS), disease free survival (DFS), progression-free survival (PFS) as well as their 95% confidence intervals (95%CIs) were used to assess the influence of miR-20a expression on patient prognosis. Odds ratio (OR) and 95%CIs were applied to evaluate the correlation between miR-20a expression and clinicopathological characteristics. Results Based on the OS analyzed by log rank tests, there was a significant association between miR-20a levels and OS by fixed effects model. By subgroup analyses, the significance was also observed in the studies of specimen derived from blood and gastrointestinal cancer group. The independent prognostic role of miR-20a expression for the OS was observed significantly by fixed effects model. In addition, we observed significant association between miR-20a expression levels and DFS of log rank tests, DFS of cox regression. Significant relation of gender/differentiation and the expression level of miR-20a was identified. Conclusions Base on the findings, the elevated miR-20a expression level is related to poor prognosis of gastrointestinal cancer patients. As for other types of carcinomas, the results are still not stable and more studies are required to further identify miR-20a prognostic values. In addition, miR-20a expression level is relatively higher in women than that in men, and increased miR-20a expression level is linked to poor tumor differentiation.

Abstract Biofilms have been related to the persistence of infections on medical implants, and these cannot be eradicated because of the resistance of biofilm structures. Therefore, a biocompatible phototherapeutic system is developed composed of MoS2, IR780 photosensitizer, and arginine–glycine–aspartic acid–cysteine (RGDC) to safely eradicate biofilms on titanium implants within 20 min. The magnetron‐sputtered MoS2 film possesses excellent photothermal properties, and IR780 can produce reactive oxygen species (ROS) with the irradiation of near‐infrared (NIR, λ = 700–1100 nm) light. Consequently, the combination of photothermal therapy (PTT) and photodynamic therapy (PDT), assisted by glutathione oxidation accelerated by NIR light, can provide synergistic and rapid killing of bacteria, i.e., 98.99 ± 0.42% eradication ratio against a Staphylococcus aureus biofilm in vivo within 20 min, which is much greater than that of PTT or PDT alone. With the assistance of ROS, the permeability of damaged bacterial membranes increases, and the damaged bacterial membranes become more sensitive to heat, thus accelerating the leakage of proteins from the bacteria. In addition, RGDC can provide excellent biosafety and osteoconductivity, which is confirmed by in vivo animal experiments.