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To improve the corrosion resistance of biodegradable Mg alloys, WE43 alloys were implanted with Fe, Ti, Zn and Zr ions at the same implantation dose. The surface morphology, valence state of elements, nano-hardness (NH), elastic modulus (EM), degradation rate and in vitro cell experiments of the modified WE43 alloys were systematically studied. A modified layer composed of Mg, MgO, the implanted elements and their oxides was formed on the modified alloys. Since high-speed metal ions caused severe surface lattice damage, the surface hardness of the substrate considerable increased. Electrochemical tests demonstrated a substantial enhancement in the corrosion resistance of the modified alloys via the implantation of Ti and Zr ions, resulting in a reduction of the corrosion current density to 88.1 ± 9.9 and 15.6 ± 11.4 µA cm−2, respectively, compared with the implantation of Fe and Zn ions. Biocompatibility tests showed that the implantation of Fe, Ti, Zn and Zr ions enhanced the anticoagulant and hemolytic resistance of the WE43 alloy. All surface-modified samples showed negligible cytotoxicity (0–1) at 12.5% extract concentration. Moreover, the alloys implanted with Fe, Ti and Zn ions significantly promoted proliferation of human umbilical vein endothelial cells (HUVEC) compared with the unmodified alloy. The results demonstrate that Ti ion implantation is the best choice for WE43 alloy modification to achieve outstanding corrosion resistance and biocompatibility.

Biomass activated carbon regeneration technology is widely used for environmental treatment and resource recovery. Various regeneration methods are available, including thermal, chemical, microwave, electrochemical, biological, wet oxidation, supercritical fluid, and ozone regeneration. Among these methods, thermal regeneration is the most widely used. Chemical regeneration is a simple and cost-effective option. Microwave regeneration allows for accurate control of regeneration parameters and quick processing of spent activated carbon. Electrochemical regeneration can be operated at low temperatures and has good regeneration stability. Biological regeneration technology is a more environmentally friendly option as it can reduce the use of chemicals. Wet oxidation regeneration technology can treat activated carbon with less loss of quality and lower energy consumption. Supercritical fluid regeneration technology uses recyclable and non-polluting solvents. Ozone technology is another option for regenerating spent activated carbon at room temperature and pressure, which can be beneficial for the process economics. The article reviews these technologies and provides an analysis of each method′s regeneration mechanism, technical characteristics, and current research status.

To address the issues of low bioavailability, degradation during processing, and limited use in precision nutrition of anthocyanins (ACNs). ACNs nanoparticles using ACNs as the core, soybean lecithin constructed-Liposome (Lipo), and Gum Arabic (GA) as the carrier were prepared in this study, namely Liposome/Gum Arabic-anthocyanins (Lipo/GA-ACNs) nanoparticles. In this study, nanoparticles of ACNs with ACNs as the core and liposomes (Lipo) constructed using soy lecithin and gum arabic (GA) as carriers, namely liposome/gum arabic-anthocyanins (Lipo/GA-ACNs) nanoparticles, were prepared. Environmental factors and in vitro simulated digestion on the stability of Lipo/GA-ACNs nanoparticles with various formulations were investigated. Additionally, the in vitro lipid-lowering activity of Lipo/GA-ACNs nanoparticles after digestion was examined. Results showed that Lipo/GA-ACNs nanoparticles had good stability under simulated thermal processing and different ion environments. When the ACNs to GA mass ratio was 1:10, the Lipo/GA-ACNs nanoparticles inhibited lipid droplet accumulation and reactive oxygen species accumulation in HepG-2 cells 3.8% and 1.99% more effectively than ACNs after simulated digestion. This study concluded that Lipo/1.0GA was a promising oral delivery system to deliver ACNs and achieve liver lipid-lowering, with the potential to be developed into functional foods with precision nutritional properties.

Abstract Immunotherapy has revolutionized the treatment of cancer. However, its efficacy remains to be optimized. There are at least two major challenges in effectively eradicating cancer cells by immunotherapy. Firstly, cancer cells evade immune cell killing by down-regulating cell surface immune sensors. Secondly, immune cell dysfunction impairs their ability to execute anti-cancer functions. Radiotherapy, one of the cornerstones of cancer treatment, has the potential to enhance the immunogenicity of cancer cells and trigger an anti-tumor immune response. Inspired by this, we fabricate biofunctionalized liposome-like nanovesicles (BLNs) by exposing irradiated-cancer cells to ethanol, of which ethanol serves as a surfactant, inducing cancer cells pyroptosis-like cell death and facilitating nanovesicles shedding from cancer cell membrane. These BLNs are meticulously designed to disrupt both of the aforementioned mechanisms. On one hand, BLNs up-regulate the expression of calreticulin, an “eat me” signal on the surface of cancer cells, thus promoting macrophage phagocytosis of cancer cells. Additionally, BLNs are able to reprogram M2-like macrophages into an anti-cancer M1-like phenotype. Using a mouse model of malignant pleural effusion (MPE), an advanced-stage and immunotherapy-resistant cancer model, we demonstrate that BLNs significantly increase T cell infiltration and exhibit an ablative effect against MPE. When combined with PD-1 inhibitor (α-PD-1), we achieve a remarkable 63.6% cure rate (7 out of 11) among mice with MPE, while also inducing immunological memory effects. This work therefore introduces a unique strategy for overcoming immunotherapy resistance.

Abstract Background The risk factors associated with niche on the cesarean scar have been reported, however, the degree of these factors associated with large niche and the accumulation effects of these risk factors on the development of large niche are unclear. Methods Large niche was evaluated by transvaginal sonography during mid-follicular phase. Logistic regression model was used to assess 32 risk factors by univariate analysis. Then, a scoring model based on the screened risk factors was generated. The performance of this model was evaluated by area under curve (AUC). Finally, the scoring model was applied in 123 women to assess the external validation. Result(s) In the training cohort study, 163 women were diagnosed with large niche. The final scoring model involves eight risk factors with the rating scores including age at delivery (30–34 years: 1 point; ≥ 35 years: 4.5 points), retroflexed uterus (8.5 points), meconium-stained amniotic fluid (4.5 points), twice CSs (4.0 points), postpartum endometritis (4.5 points), premature rupture of membranes (2.5 points), intrahepatic cholestasis of pregnancy (mild to moderate: 3 points; severe: 6.5 points), and cervical dilatation (1-3 cm: 2.0 points; 4-10 cm: 4.5 points). The accumulation effect with a cut-off value of 8.0 in the scoring was associated with the large niche after CS. Conclusion(s) This is the first scoring model to objectively quantify the risk of a large niche after CS. Optimal risk factors control by avoiding high score factors and multiple factors accumulation may eliminate the risk of large niche development.

Abstract In order to treat dyes in the wastewater of the printing industry and to reutilize walnut shell (WS) waste generate economic benefits, supercritical carbon dioxide (SC-CO2) pretreatment technology was developed to prepare porous biochar as a precursor for adsorption material. Orthogonal experiments were conducted at the temperatures of 200, 300, and 400 ℃ with durations of 20, 40, and 60 min, and a control group was set up using N2 pretreatment. Then, KOH activation was employed to prepare biochar adsorption material. The biochars were analyzed and characterized using TGA, BET, SEM, FT-IR, and XRD, and the liquid and gas phase products of the pretreatment process were analyzed semi-quantitatively and quantitatively using GC–MS and gas chromatography. Methylene blue (MB) dye was selected as an indicator to measure the adsorption capacity of biochar, and adsorption kinetics were analyzed based on the data. The results indicate that pretreatment with SC-CO2 effectively enhanced the performance and yield of the activated carbon. The highest specific surface area increased by 18%, and the maximum adsorption of MB increased by 23% compared to the N2 control group. The yield increased by 8–262% and the specific surface area increased by 50–192% compared to the direct activation of walnut shell (WS). During the pretreatment processes for the preparation of biochar adsorption material with the best specific surface area, phenol-enriched bio-oil was produced as a by-product which has economic value. Graphical Abstract

Abstract Background Glioblastoma (GBM) is the most common malignant tumor of the central nervous system. It is an aggressive tumor characterized by rapid proliferation, diffuse tumor morphology, and poor prognosis. Unfortunately, current treatments, such as surgery, radiotherapy, and chemotherapy, are unable to achieve good outcomes. Therefore, there is an urgent need to explore new treatment targets. A detailed mechanistic exploration of the role of the nuclear pore transporter KPNB1 in GBM is lacking. This study demonstrated that KPNB1 regulated GBM progression through a transcription factor YBX1 to promote the expression of post-protrusion membrane protein NLGN3. This regulation was mediated by the deubiquitinating enzyme USP7. Methods A tissue microarray was used to measure the expression of KPNB1 and USP7 in glioma tissues. The effects of KPNB1 knockdown on the tumorigenic properties of glioma cells were characterized by colony formation assays, Transwell migration assay, EdU proliferation assays, CCK-8 viability assays, and apoptosis analysis using flow cytometry. Transcriptome sequencing identified NLGN3 as a downstream molecule that is regulated by KPNB1. Mass spectrometry and immunoprecipitation were performed to analyze the potential interaction between KPNB1 and YBX1. Moreover, the nuclear translocation of YBX1 was determined with nuclear-cytoplasmic fractionation and immunofluorescence staining, and chromatin immunoprecipitation assays were conducted to study DNA binding with YBX1. Ubiquitination assays were performed to determine the effects of USP7 on KPNB1 stability. The intracranial orthotopic tumor model was used to detect the efficacy in vivo. Results In this study, we found that the nuclear receptor KPNB1 was highly expressed in GBM and could mediate the nuclear translocation of macromolecules to promote GBM progression. Knockdown of KPNB1 inhibited the progression of GBM, both in vitro and in vivo. In addition, we found that KPNB1 could regulate the downstream expression of Neuroligin-3 (NLGN3) by mediating the nuclear import of transcription factor YBX1, which could bind to the NLGN3 promoter. NLGN3 was necessary and sufficient to promote glioma cell growth. Furthermore, we found that deubiquitinase USP7 played a critical role in stabilizing KPNB1 through deubiquitination. Knockdown of USP7 expression or inhibition of its activity could effectively impair GBM progression. In vivo experiments also demonstrated the promoting effects of USP7, KPNB1, and NLGN3 on GBM progression. Overall, our results suggested that KPNB1 stability was enhanced by USP7-mediated deubiquitination, and the overexpression of KPNB1 could promote GBM progression via the nuclear translocation of YBX1 and the subsequent increase in NLGN3 expression. Conclusion This study identified a novel and targetable USP7/KPNB1/YBX1/NLGN3 signaling axis in GBM cells.

Abstract Background The development of radioresistance seriously hinders the efficacy of radiotherapy in lung cancer. However, the underlying mechanisms by which radioresistance occurs are still incompletely understood. The N6-Methyladenosine (m6A) modification of RNA is involved in cancer progression, but its role in lung cancer radioresistance remains elusive. This study aimed to identify m6A regulators involved in lung cancer radiosensitivity and further explore the underlying mechanisms to identify therapeutic targets to overcome lung cancer radioresistance. Methods Bioinformatic mining was used to identify the m6A regulator IGF2BP2 involved in lung cancer radiosensitivity. Transcriptome sequencing was used to explore the downstream factors. Clonogenic survival assays, neutral comet assays, Rad51 foci formation assays, and Annexin V/propidium iodide assays were used to determine the significance of FBW7/IGF2BP2/SLC7A5 axis in lung cancer radioresistance. Chromatin immunoprecipitation (ChIP)-qPCR analyses, RNA immunoprecipitation (RIP) and methylated RNA immunoprecipitation (MeRIP)-qPCR analyses, RNA pull-down analyses, co-immunoprecipitation analyses, and ubiquitination assays were used to determine the feedback loop between IGF2BP2 and SLC7A5 and the regulatory effect of FBW7/GSK3β on IGF2BP2. Mice models and tissue microarrays were used to verify the effects in vivo. Results We identified IGF2BP2, an m6A “reader”, that is overexpressed in lung cancer and facilitates radioresistance. We showed that inhibition of IGF2BP2 impairs radioresistance in lung cancer both in vitro and in vivo. Furthermore, we found that IGF2BP2 enhances the stability and translation of SLC7A5 mRNA through m6A modification, resulting in enhanced SLC7A5-mediated transport of methionine to produce S-adenosylmethionine. This feeds back upon the IGF2BP2 promoter region by further increasing the trimethyl modification at lysine 4 of histone H3 (H3K4me3) level to upregulate IGF2BP2 expression. We demonstrated that this positive feedback loop between IGF2BP2 and SLC7A5 promotes lung cancer radioresistance through the AKT/mTOR pathway. Moreover, we found that the ubiquitin ligase FBW7 functions with GSK3β kinase to recognize and degrade IGF2BP2. Conclusions Collectively, our study revealed that the m6A “reader” IGF2BP2 promotes lung cancer radioresistance by forming a positive feedback loop with SLC7A5, suggesting that IGF2BP2 may be a potential therapeutic target to control radioresistance in lung cancer.

Abstract Background There is conclusive evidence of a multifaceted and bidirectional relationship between loneliness and depression and anxiety. Nonetheless, more extensive research is needed to examine their relationships at a more granular level. This study employed a network analysis approach to identify the pathological mechanisms underpinning those relationships and to identify important bridge nodes as potential targets for intervention. Methods 941 University students were included in this study. The ULS-6 (the short-form UCLA Loneliness Scale) was used to assess loneliness, the PHQ-9 (Patient Health questionnaire-9) and GAD-7 (Generalized anxiety disorder 7-item) scales were used to assess the symptoms of depression and anxiety. We constructed two network structures of loneliness-anxiety and loneliness-depression and computed bridge expected influence for each symptom. In addition, we showed a flow network of “Suicide” containing symptoms of depression and loneliness. Results All edges were positive in both networks constructed and the strongest edges were present within disorder communities. The overall connection between loneliness and depression was stronger compared to anxiety. The results demonstrated that the loneliness item “People are around me but not with me” was identified as bridge symptom in both networks. Furthermore, “Suicide” was directly connected to five symptoms of depression and four items of loneliness, with the strongest connections being between it and “Feeling of worthlessness” and “Psychomotor agitation/retardation”. Conclusions Our findings provide a more nuanced explanation of the link between loneliness and depression and anxiety. The results identified the bridge symptom “People are around me but not with me”, which had the strongest effect on enhancing symptoms of depression and anxiety. Clinical improvements based on the findings of this study and the impact of the intervention are discussed.

The annual degradation of biological soil health within Northeast China (NC), specifically in the context of spring maize (Zea mays L.) cultivation, has been a growing concern. Improving straw management is a potential strategy to ameliorate this ongoing deterioration. This study aimed to determine the responses of soil gaseous nitrogen (N) losses to deep-plowed maize straw into the surface soil layer. The field experiment was conducted from 2019 to 2021 with six treatments: no straw (S0N0), half straw (7.5 ​t ​ha−1, S0.5N0), and full straw return (15 ​t ​ha−1, S1N0) without N fertilizer; no straw (S0N200), half straw (S0.5N200), and full straw return (S1N200) with 200 ​kg ​N ha−1. The results indicated that the cumulative ammonia (NH3) volatilization increased by 74.6% and 120.0% in S0.5N200 and S1N200 compared with S0N200, respectively. The cumulative nitrous oxide (N2O) emissions were lower in S0.5 and S1 than in S0 by 48.8% and 45.3%, respectively. The soil NO3−-N content in the 0−80 ​cm layer was reduced by 48.5% and 56.5% in S0.5 and S1, respectively, compared with S0. However, the agronomic efficiency of N (AEN) decreased by 5.4% and 17.6% in S0.5 and S1, respectively, compared with S0 in 2021. Overall, the deep incorporation of maize straw into farmland in NC primarily increased the NH3 emission in the short term. However, it was beneficial for reducing the N2O emission and avoiding N leaching into deeper soil layers. An increase in N fertilization would better meet the demand for maize growth, thus enhancing the yield. In the future, controlling the NH3 emission to improve N use efficiency can further unleash the potential of the straw return to increase soil N reservoirs, enhance ecological benefits, and maintain food security.

Calcium-phosphate (CaP) coatings have been widely used in the field of biodegradable magnesium alloys. This paper provides a novel pretreatment method before depositing CaP coatings on the surface of WE43 biomedical magnesium alloys. The surface morphology, phase composition, corrosion resistance and in vitro biological properties of coated samples were investigated. The results showed that a uniform and dense CaP coating formed on the surface of WE43 magnesium alloy pretreated by FCVA (Filtered Cathode Vacuum Arc Technology) possessed better corrosion resistance. Compared with WE43 substrate, Icorr of FCVA/CaP sample decreased by 85.56%. The ALP activity, OD value of COL secretion and mineralization of FCVA/CaP sample reached nearly 2 times higher than that of bare WE43.

Abstract Background Acute myeloid leukaemia (AML) is a haematological malignancy with unfavourable prognosis. Despite the effectiveness of chemotherapy and targeted therapy, relapse or drug resistance remains a major threat to AML patients. N6‐methyladenosine (m6A) RNA methylation and super‐enhancers (SEs) are extensively involved in the leukaemogenesis of AML. However, the potential relationship between m6A and SEs in AML has not been elaborated. Methods Chromatin immunoprecipitation (ChIP) sequencing data from Gene Expression Omnibus (GEO) cohort were analysed to search SE‐related genes. The mechanisms of m6 A‐binding proteins IGF2BP2 and IGF2BP3 on DDX21 were explored via methylated RNA immunoprecipitation (MeRIP) assays, RNA immunoprecipitation (RIP) assays and luciferase reporter assays. Then we elucidated the roles of DDX21 in AML through functional assays in vitro and in vivo. Finally, co‐immunoprecipitation (Co‐IP) assays, RNA sequencing and ChIP assays were performed to investigate the downstream mechanisms of DDX21. Results We identified two SE‐associated transcripts IGF2BP2 and IGF2BP3 in AML. High enrichment of H3K27ac, H3K4me1 and BRD4 was observed in IGF2BP2 and IGF2BP3, whose expression were driven by SE machinery. Then IGF2BP2 and IGF2BP3 enhanced the stability of DDX21 mRNA in an m6A‐dependent manner. DDX21 was highly expressed in AML patients, which indicated a poor survival. Functionally, knockdown of DDX21 inhibited cell proliferation, promoted cell apoptosis and led to cell cycle arrest. Mechanistically, DDX21 recruited transcription factor YBX1 to cooperatively trigger ULK1 expression. Moreover, silencing of ULK1 could reverse the promoting effects of DDX21 overexpression in AML cells. Conclusions Dysregulation of SE‐IGF2BP2/IGF2BP3‐DDX21 axis facilitated the progression of AML. Our findings provide new insights into the link between SEs and m6A modification, elucidate the regulatory mechanisms of IGF2BP2 and IGF2BP3 on DDX21, and reveal the underlying roles of DDX21 in AML.

Bromodomain‐containing protein 4 (BRD4) inhibitors have been clinically developed to treat acute myeloid leukemia (AML), but their application is limited by the possibility of drug resistance, which is reportedly associated with the activation of the WNT/β‐catenin pathway. Meanwhile, homoharringtonine (HHT), a classic antileukemia drug, possibly inhibits the WNT/β‐catenin pathway. In this study, we attempted to combine a novel BRD4 inhibitor (ACC010) and HHT to explore their synergistic lethal effects in treating AML. Here, we found that co‐treatment with ACC010 and HHT synergistically inhibited cell proliferation, induced apoptosis, and arrested the cell cycle in FMS‐like tyrosine kinase 3‐internal tandem duplication (FLT3‐ITD)–positive AML cells in vitro, and significantly inhibiting AML progression in vivo. Mechanistically, ACC010 and HHT cooperatively downregulated MYC and inhibited FLT3 activation. Further, when HHT was added, ACC010‐resistant cells demonstrated a good synergy. We also extended our study to the mouse BaF3 cell line with FLT3‐inhibitor‐resistant FLT3‐ITD/tyrosine kinase domain mutations and AML cells without FLT3‐ITD. Collectively, our results suggested that the combination treatment of ACC010 and HHT might be a promising strategy for AML patients, especially those carrying FLT3‐ITD.

Abstract Background Glioblastoma (GBM) is recognized as among the most aggressive forms of brain tumor. Patients typically present with a five-year survival rate of less than 6% with traditional surgery and chemoradiotherapy, which calls for novel immunotherapies like chimeric antigen receptor T (CAR-T) cells therapy. In response to endoplasmic reticulum (ER) stress in multiple tumor cells including GBM, the glucose-regulated protein 78 (GRP78) expression increases and the protein is partially translocated to the cell surface, while it is restricted to the cytoplasm and the nucleus in normal cells. Methods In this study, to target the cell surface GRP78 (csGRP78), CAR-T cells based on its binding peptide were generated. In vitro two GBM cell lines and glioma stem cells (GSCs) were used to confirm the localization of csGRP78 and the cytotoxicity of the CAR-T cells. In vivo a GBM xenograft model was used to assess the killing activity and the safety of the CAR-T cells. Results We confirmed the localization of csGRP78 at the cell surface of two GBM cell lines (U-251MG and U-87MG) and in GSCs. Co-culture experiments revealed that the CAR-T cells could specifically kill the GBM tumor cells and GSCs with specific IFN-γ release. Furthermore, in the tumor xenograft model, the CAR-T cells could decrease the number of GSCs and significantly suppress tumor cell growth. Importantly, we found no obvious off-target effects or T cell infiltration in major organs following systemic administration of these cells. Conclusions The csGRP78 targeted CAR-T cells efficiently kill GBM tumor cells and GSCs both in vitro and in vivo, and ultimately suppress the xenograft tumors growth without obvious tissue injuries. Therefore, our study demonstrates that csGRP78 represents a valuable target and the csGRP78-targeted CAR-T cells strategy is an effective immunotherapy against GBM.

Intercropping is a vital cropping system that can create a conducive growth environment for crops and enhance land productivity. Tiger nuts (Cyperus esculentus L.) have high oil content and are adaptable to various soil types, making them a promising new oil crop with significant development potential. This study evaluated the plant height, leaf area, tiller numbers, biomass, land equivalent ratio (LER), and root morphological characteristics of tiger nuts. The agronomic traits and root distribution of tiger nuts and other crops were further investigated to achieve the goal of high yield for tiger nuts. Seven intercropping systems were implemented in the experiment: maize–tiger nut intercropping (MT), soybean–tiger nut intercropping (ST), cotton–tiger nut intercropping (CT), monoculture tiger nut (T), monoculture maize (M), monoculture soybean (S), and monoculture cotton (C). The results indicated that under different planting systems, the agronomic traits of tiger nuts in MT and ST modes were superior, with plant height and tiller numbers increasing by 7.6% to 11.6%. However, the plant height and Soil Plant Analysis Development (SPAD) values in CT mode were slightly lower than in T mode. Additionally, intercropping reduced the leaf area by 6.2% to 37.9%. Root development was more pronounced in intercropping modes, with the ST mode showing the most significant improvement, increasing the 0–20 cm root length density (RLD) by 12.2% to 45.7%. Therefore, each of the three intercropping modes demonstrated distinct advantages. The LER of the intercropping systems ranged from 1.10 to 1.24, enhancing land utilization, with tiger nuts being the dominant species. Compared to monoculture, the ST mode exhibited the best overall effect. Understanding the impact of different planting systems on tiger nuts provides valuable insights for developing tiger nut cultivation in Xinjiang.

Radiotherapy (RT) serves as the primary treatment for solid tumors. Its potential to incite an immune response against tumors both locally and distally profoundly impacts clinical outcomes. However, RT may also promote the accumulation of immunosuppressive cytokines and immunosuppressive cells, greatly impeding the activation of antitumor immune responses and substantially limiting the effectiveness of RT. Therefore, regulating post-RT immunosuppression to steer the immune milieu toward heightened activation potentially enhances RT’s therapeutic potential. Cytokines, potent orchestrators of diverse cellular responses, play a pivotal role in regulating this immunosuppressive response. Identifying and promptly neutralizing early released immunosuppressive cytokines are a crucial development in augmenting RT’s immunomodulatory effects. To this end, we conducted a screen of immunosuppressive cytokines following RT and identified macrophage colony-stimulating factor (MCSF) as an early up-regulated and persistent immune suppressor. Single-cell sequencing revealed that the main source of up-regulated MCSF derived from tumor cells. Mechanistic exploration revealed that irradiation-dependent phosphorylation of the p65 protein facilitated its binding to the MCSF gene promoter, enhancing transcription. Knockdown and chemical inhibitor experiments conclusively demonstrated that suppressing tumor cell-derived MCSF amplifies RT’s immune-activating effects, with optimal results achieved by early MCSF blockade after irradiation. Additionally, we validated that MCSF acted on macrophages, inducing the secretion of a large number of inhibitory cytokines. In summary, we propose a novel approach to enhance the immune activation effects of RT by blocking the MCSF-CSF1R signaling pathway early after irradiation.

The anisotropy of energetic particles provides essential information to help resolve the underlying fundamental physics of their spatial distributions, injection, acceleration, and transport processes. In this work, we report an energetic ion enhancement that is characterized by very large and long-lasting anisotropies observed by STEREO A and Solar Orbiter, which are nearly aligned along the same nominal Parker spiral. This ion enhancement appears at the rising phase of a widespread solar energetic particle event that was associated with the farside coronal mass ejection on 2022 February 15. According to our analysis, the long-lasting anisotropy resulted from the continuous injection of energetic ions from a well-connected particle source located beyond the STEREO A’s orbit. Solar Orbiter also observed an interval of very large anisotropy dominated exclusively by sunward streaming ions but with the additional implication that it detected the very early phase of ion injections onto magnetic field lines that newly connected to the particle source, which is likely the first reported event of this kind. These results further illustrate how energetic particle anisotropy information, in particular from multiple observer locations, can be used to disentangle the sources and transport processes of energetic ions, even when their heliospheric context is not simple.

Abstract Background Identifying therapeutic targets and prognostic biomarkers significantly contributes to individualized treatment of acute myeloid leukemia (AML). Dihydropyrimidinase‐like 2 (DPYSL2) expression was decreased in homoharringtonine (HHT)‐resistant AML cells, which were established by our group. DPYSL2 plays an important role in axon growth and has oncogene effect in glioblastoma. However, little research has been conducted to investigate the function of DPYSL2 in AML pathogenesis. Methods Auto‐docking was used to reveal the targeting relationship between HHT and DPYSL2. Overall survival (OS), event‐free survival (EFS), and relapse‐free survival (RFS) were used to evaluate the prognostic impact of DPYSL2 for AML. ShRNA was used to knockdown the expression of SPATS2L. Apoptosis was assessed by flow cytometry. In vivo growth and survival were assessed using a xenotransplantation mice model. RNA sequencing was performed to elucidate the molecular mechanisms underlying the role of SPATS2L in AML and were confirmed by Western blot. Results We found DPYSL2 was the target of HHT. Next, we found AML cell lines and patients had higher DPYSL2 expression levels than the normal samples. Further multivariate analysis demonstrated that high DPYSL2 expression was an independent poor prognostic factor for OS, EFS, and RFS in AML. Inhibition of DPYSL2 expression suppressed cell growth, induced apoptosis in AML cell lines, and prolonged the survival of AML xenograft NCG mice. Through RNA‐seq analysis from TCGA and our data, the JAK2/STAT3/STAT5‐PI3K P85/AKT/GSK3b axis was thought to be the critical pathway in regulating DPYSL2 in AML development. Conclusions We first time confirmed that DPYSL2 was a target of HHT and played an oncogene role in AML by regulating JAK/STAT signaling pathway. Therefore, DPYSL2 could serve as a novel prognostic marker and therapeutic target for AML treatment.

Abstract Background Spermatogenesis associated serine rich 2 like (SPATS2L) was highly expressed in homoharringtonine (HHT) resistant acute myeloid leukemia (AML) cell lines. However, its role is little known in AML. The present study aimed to investigate the function of SPATS2L in AML pathogenesis and elucidate the underlying molecular mechanisms. Methods Overall survival (OS), event-free survival (EFS), relapse-free survival (RFS) were used to evaluate the prognostic impact of SPATS2L for AML from TCGA database and ourcohort. ShRNA was used to knockdown the expression of SPATS2L. Apoptosis was assessed by flow cytometry. The changes of proteins were assessed by Western blot(WB). A xenotransplantation mice model was used to evaluate in vivo growth and survival. RNA sequencing was performed to elucidate the molecular mechanisms underlying the role of SPATS2L in AML. Results SPATS2L expression increased with increasing resistance indexes(RI) in HHT-resistant cell lines we had constructed. Higher SPATS2L expression was observed in intermediate/high-risk patients than in favorable patients. Meanwhile, decreased SPATS2L expression was observed in AML patients achieving complete remission (CR). Multivariate analysis showed high SPATS2L expression was an independent poor predictor of OS, EFS, RFS in AML. SPATS2L knock down (KD) suppressed cell growth, induced apoptosis, and suppressed key proteins of JAK/STAT pathway, such as JAK2, STAT3, STAT5 in AML cells. Inhibiting SPATS2L expression markedly enhanced the pro-apoptotic effects of traditional chemotherapeutics (Ara-c, IDA, and HHT). Conclusions High expression of SPATS2L is a poor prognostic factor in AML, and targeting SPATS2L may be a promising therapeutic strategy for AML patients.

Abstract Background Despite advances in targeted agent development, effective treatment of acute myeloid leukemia (AML) remains a major clinical challenge. The B-cell lymphoma-2 (BCL-2) inhibitor exhibited promising clinical activity in AML, acute lymphoblastic leukemia (ALL) and diffuse large B-cell lymphoma (DLBCL) treatment. APG-2575 is a novel BCL-2 selective inhibitor, which has demonstrated anti-tumor activity in hematologic malignancies. Homoharringtonine (HHT), an alkaloid, exhibited anti-AML activity. Methods The synergistic effects of APG-2575 and HHT were studied in AML cell lines and primary samples. MTS was used to measure the cell viability. Annexin V/propidium iodide staining was used to measure the apoptosis rate by flow cytometry. AML cell xenografted mouse models were established to evaluate the anti-leukemic effect of BCL-2 inhibitor, HHT and their combination in vivo. Western blot was used to determine the expression of related proteins. Results APG-2575 showed comparable anti-leukemic effect to the FDA-approved BCL-2 inhibitor ABT-199 in vitro and in vivo. Combined treatment of HHT with APG-2575 synergistically inhibited AML cell growth and engraftment. Mechanistically, HHT promoted degradation of myeloid cell leukemia-1 (MCL-1), which was reported to induce BCL-2 inhibitor resistant, through the PI3K/AKT/GSK3β signaling pathway. Conclusion Our results provide an effective AML treatment strategy through combination of APG-2575 and HHT, which is worthy of further clinical research.

Non-B-cell acute leukemia is a term that encompasses T-cell acute lymphoblastic leukemia (T-ALL) and acute myeloid leukemia (AML). Currently, the therapeutic effectiveness of existing treatments for refractory or relapsed (R/R) non-B-cell acute leukemia is limited. In such situations, chimeric antigen receptor (CAR)-T cell therapy may be a promising approach to treat non-B-cell acute leukemia, given its promising results in B-cell acute lymphoblastic leukemia (B-ALL). Nevertheless, fratricide, malignant contamination, T cell aplasia for T-ALL, and specific antigen selection and complex microenvironment for AML remain significant challenges in the implementation of CAR-T therapy for T-ALL and AML patients in the clinic. Therefore, designs of CAR-T cells targeting CD5 and CD7 for T-ALL and CD123, CD33, and CLL1 for AML show promising efficacy and safety profiles in clinical trials. In this review, we summarize the characteristics of non-B-cell acute leukemia, the development of CARs, the CAR targets, and their efficacy for treating non-B-cell acute leukemia.

Abstract Background Fatty acid oxidation (FAO) provides an important source of energy to promote the growth of leukemia cells. Carnitine palmitoyltransferase 1a(CPT1a), a rate-limiting enzyme of the essential step of FAO, can facilitate cancer metabolic adaptation. Previous reports demonstrated that CPT1a acts as a potential molecular target in solid tumors and hematologic disease. However, no systematic study was conducted to explore the prognostic value of CPT1a expression and possible treatment strategies with CPT1a inhibitor on acute myeloid leukemia (AML). Methods The expression of CPT1a in 325 cytogenetically normal AML (CN-AML) patients was evaluated using RT-PCR. The combination effects of ST1326 and ABT199 were studied in AML cells and primary patients. MTS was used to measure the cell proliferation rate. Annexin V/propidium iodide staining and flow cytometry analysis was used to measure the apoptosis rate. Western blot was used to measure the expression of Mcl-1. RNAseq and GC-TOFMS were used for genomic and metabolic analysis. Results In this study, we found AML patients with high CPT1a expression (n = 245) had a relatively short overall survival (P = 0.01) compared to patients in low expression group (n = 80). In parallel, downregulation of CPT1a inhibits proliferation of AML cells. We also conducted genomic and metabolic interactive analysis in AML patients, and found several essential genes and pathways related to aberrant expression of CPT1a. Moreover, we found downregulation of CPT1a sentitized BCL-2 inhibitor ABT199 and CPT1a-selective inhibitor ST1326 combined with ABT199 had a strong synergistic effect to induce apoptosis in AML cells and primary patient blasts for the first time. The underlying synergistic mechanism might be that ST1326 inhibits pGSK3β and pERK expression, leading to downregulation of Mcl-1. Conclusion Our study indicates that overexpression of CPT1a predicts poor clinical outcome in AML. CPT1a-selective inhibitor ST1326 combined with Bcl-2 inhibitor ABT199 showed strong synergistic inhibitory effects on AML.

Peripheral T-cell lymphomas (PTCLs) are highly heterogeneous and present significant treatment challenges. Immune checkpoint therapies, such as PD-1 and CTLA-4 inhibitors, have significantly changed the clinical management paradigm of tumors. The roles of immune checkpoints in PTCL and related agents have been actively explored over recent years. PD-1 and PD-L1 expression is detectable in both PTCL and immune cells within the tumor microenvironment and forms the basis for the exploration of antibodies targeting these proteins. Such antibodies are currently being investigated in clinical trials to guide individualized therapy. PD-1/PD-L1 inhibitors alone and in combination with chemotherapy, radiotherapy, or targeted therapy have shown broad clinical efficacy and improved the survival of cancer patients. Studies of other immune checkpoint proteins, such as CTLA-4, TIM-3, LAG-3, and TIGIT, are likely to provide potential novel targets for immunotherapy. Here, we review the role of and recent advances in immune checkpoint blockade in common subtypes of PTCL, focusing on the anti-tumor immune responses to PD-1/PD-L1 blockers.

High yields and low carbon emissions are new challenges for modern crop production. Balancing the crop yield and reducing greenhouse gas (GHG) emissions has become a new field of agronomic technology innovation. Cereal–legume intercropping is a typical diversification planting system, which has been expected to achieve the dual goals of high production and low GHG emissions. However, the synergistic effect of integrating various technologies in an intercropping system on GHG emissions and whether it will achieve the high yield and low emissions goal remains to be determined. Therefore, bibliometric analysis has investigated the worldwide development trend of cereal–legume intercropping designs. The literature on the GHG emissions of the cereal–legume intercropping system was summarized. Additionally, the effects and mechanisms of different agricultural management methods regarding soil nitrous oxide and carbon dioxide emissions in the cereal–legume intercropping system were summarized. The research on GHG emissions of cereal–legume intercropping systems in non-growing seasons must be revised. In situ observations of GHG emissions from intercropping systems in different regions should be strengthened. This work is valuable in supporting and evaluating the potential of GHG reduction in a cereal–legume intercropping system in various farming areas.

Graves’ disease (GD) is a well-known organ-specific autoimmune disease characterized by hyperthyroidism, goiter, and exophthalmos. The incidence of GD is approximately 2.0–3.0% in China and 0.5–2.0% in Western countries. Due to the complex pathogenesis and etiology of GD, current treatment methods have great side effects that seriously endanger human health. Therefore, it is particularly important to understand the pathogenesis of GD. Various studies have shown that genetics, epigenetics, cellular immunology, and gut microbiota are all involved in the development of GD. Genetically, CD25 gene and VDR gene polymorphisms are involved in the development of GD by increasing the ratio of Th17/Treg cells. Epigenetically, miR-23a-3p and lncRNA-MEG3 lead to Th17/Treg imbalance and participate in the progression of GD. Moreover, commensal microbe deletion can disrupt Th17/Treg balance and participate in the occurrence of GD. The imbalance of Th17/Treg cells induced by genetics, epigenetics, and gut microbiota plays a vital role in the pathogenesis of GD. Therefore, this article reviews the role of genetics, epigenetics, cellular immunology, and gut microbiota in the pathogenic mechanism of GD. This may lead to the development of novel therapeutic strategies and providing promising therapeutic targets.

In dryland agroecosystems, intercropping fruit trees with legumes is often an important option for maintaining and improving soil N quality and fertility. The relationships of fine root length density (FRLD), soil water content (SWC), and soil NO3−-N content (SNC) in agroforestry systems is essential for optimal orchard management. Our objective was to understand the temporal and spatial dynamics of FRLD, SWC, and SNC in an apple–soybean intercropping system and competition between species for ecological niches. We established an orchard with soybean and apple, including monoculture apple (MA), monoculture soybean (MS), and apple–soybean intercrop (AS) treatments. We collected data on the distribution of FRLD, SWC, SNC, and productivity under the MA, AS, and MS from 2020 to 2021. This study showed that AS had more FRLD compared to MA, and intercropping apple (IA) FRLD increased at 20–60 cm soil depth at 50 and 100 cm from the tree and decreased at 0–40 cm soil depth at 150 and 200 cm from the tree. Intercropping increased the SWC of the system and decreased the SNC, and the effect of intercropping was concentrated in the soybean cover area. The competition between apple and soybean reached its maximum at soybean seed filling stage, with competition occurring mainly at 100 cm from the tree and at 0–20 cm soil depth. Intercropping affected soybean growth and also reduced soybean yield with a land equivalent ratio = 1.45. By understanding the dynamics of subsoil resources in the apple–soybean intercropping system and interspecific competition, we can provide a theoretical basis for exploring the potential of sustainable intensification of agroforestry systems.

Behçet’s disease (BD) is a chronic refractory multisystem autoinflammatory disease, characterized by typical clinical features of non-specific vasculitis, oral and genital ulcers, uveitis, as well as skin lesions. The exact etiopathogenesis of BD remains unknown, existing studies have indicated that genetics and environmental factors contribute to the increased development of BD. Recently, several studies have shown that external environmental factors can affect the process of epigenetic modification, and abnormalities of epigenetic factors have been confirmed to be involved in the occurrence of BD. At the same time, abnormalities of gut microbiota (GM) in the body, have also been confirmed to participate in the pathogenesis of BD by regulating the balance of Th17/Tregs. This article reviews the pathogenesis of BD and summarizes numerous clinical studies, focusing on the mechanism of GM and epigenetic factors impacting on BD, and providing new ideas for further elucidating the pathogenesis of BD.

Agroforestry is considered a means to provide sustainable and productive agriculture. This work aims to study the effect of fruit-grass agroforestry patterns on the soil moisture, salinity, growth, and yield of fruit trees, as well as to provide a reference for the development of agroforestry complex systems in Northwest China. The study has been designed with two cropping patterns: monocropped apple and apple-ryegrass intercropping. The results showed that compared to monocropped apples, intercropped apples have increased soil moisture content by 33.38–39.02%, net photosynthetic rate by 35.33–42.26%, transpiration rate by 29.62–29.76%, and stomatal conductance by 15.65–16.55% in the 0–60 cm soil layer. Intercrop reduced the total soil salt content by 36.41–38.58%, and the intercellular CO2 concentration decreased by 5.96–6.61%. In addition, intercropping improves fruit yield and quality by improving the orchard environment and increasing tree height, breast height, north-south crown spread, and east-west crown spread. Therefore, increased yield and quality can be achieved by changing the fruit tree and ryegrass planting method, which is beneficial to the sustainable development of agriculture in Northwest China.

Background: Acute myeloid leukemia (AML) is a group of heterogeneous hematologic malignancies correlates with poor prognosis. It is important to identify biomarkers for effective treatment of AML. Kinases participate in many regulatory pathways and biological activities in AML. Previous studies demonstrated that MAP4K1, a serine/threonine kinase, was associated with immune regulation and cancer progression. However, its role and mechanism in acute myeloid leukemia (AML) have not been explored.Methods: RNA-seq profiling was performed for Homoharringtonine (HHT)-resistant and Homoharringtonine (HHT)-sensitive cell lines. Bioinformatic tools were used for differential analysis. Cell culture and transfection, Cell proliferation, apoptosis and Cell cycle assay, Quantitative RT-PCR, and Western blotting analysis were used to explore biological phenotypes in vitro.Findings: We found that MAP4K1 was highly expressed in HHT-induced resistant AML cell lines. In addition, overexpression of MAP4K1 in AML cells induced resistance of AML cells against HHT. Not only that, the findings of this study showed that overexpression of MAP4K1 was an independent risk factor that predicts poor prognosis of AML. Further, In vitro studies showed that MAP4K1 modulated cell cycle through MAPK and DNA damage/repair pathways. Therefore, MAP4K1 is a potential target for developing therapies for AML.Interpretation: This study demonstrates that MAP4K1 not only regulates HHT resistance but also independently predicts AML prognosis. In addition, understanding the regulatory mechanism of MAP4K1 reveals novel treatment strategies for resistant and refractory AML.Fundings: This work was supported by the National Natural Science Foundation of China (NSFC) (Grant No.81800199, 81670124, 82070118) and the Natural Science Foundation of Zhejiang Province (LY20H080008).

Objective This meta-analysis aimed to determine the associations between the rs3761547, rs3761548, and rs3761549 single-nucleotide polymorphisms (SNPs) of the forkhead box P3 ( FOXP3 ) gene and susceptibility to Graves’ disease (GD). Methods Case–control studies with information on the associations between the rs3761547, rs3761548, and rs3761549 FOXP3 SNPs and GD published before 01 May 2020 were identified in the PubMed, Embase, Web of Science, and China National Knowledge Infrastructure databases. Data from the studies were analyzed using RevMan version 5.3. Results Seven independent case–control studies including 4051 GD patients and 4569 controls were included in the meta-analysis. The overall pooled analysis indicated that FOXP3 /rs3761548 and FOXP3 /rs3761549 polymorphisms were significantly associated with GD susceptibility (rs3761548: A vs. C, odds ratio [OR] = 1.32, 95% confidence interval [CI] 1.05–1.67; rs3761549: TT vs. CC, OR = 1.98, 95%CI 1.49–2.65; (TT + TC) vs. CC, OR = 1.44, 95%CI 1.11–1.88). In contrast, the FOXP3 /rs3761547 polymorphism was not associated with GD susceptibility. Subgroup analysis according to ethnicity showed that rs3761548 was associated with GD in Asians but not in Caucasians, whereas rs3761549 was associated in both Asians and Caucasians. Conclusion This meta-analysis demonstrated that FOXP3 /rs3761548 and FOXP3 /rs3761549 SNPs were significantly associated with susceptibility to GD, at least in Asian populations.

Intercropping is a breakthrough in land-use optimization. This work aimed to study the effects of intercropping patterns on the growth, yield, root morphological characteristics, and interspecific competition of maize and soybean, as well as provide a reference for the development of intercropping patterns of maize and soybean in Northwest China. Three different cropping patterns were designed: monocropping maize, monocropping soybean, and maize-soybean intercropping. Agronomic traits, intercropping indicators such as land equivalent ratio (LER), aggressivity (A), competition ratio (CR), and actual yield loss (AYL), as well as root morphological characteristics were assessed. The results showed that, compared with monocropping, the intercropping maize plant height increased by 6.07–8.40%, and the intercropping soybean plant height increased by 35.27–38.94%; the root length density (RLD) of intercropping maize was higher than that of monocropping maize, the RLD of intercropping soybean was lower than that of monocropping soybean, in the 0–40 cm soil layer the intercropping increased maize RLD by 1.79–7.44% while the soybean RLD was reduced by 3.06–9.46%; the aggressivity of maize was greater than 0 and the competition ratio was greater than 1, which was the dominant species; the maize/soybean land equivalent ratio was 1.18–1.26, which improved the land utilization rate. Therefore, the effect of increasing yield can be achieved by changing the maize and soybean planting method, which is beneficial to the ecological strategy of sustainable development in the northwest region.

The quality of strawberry powder depends on the freshness of the fruit that produces the powder. Therefore, identifying whether the strawberry powder is made from freshly available, short-term stored, or long-term stored strawberries is important to provide consumers with quality-assured strawberry powder. Nevertheless, such identification is difficult by naked eyes, as the powder colours are very close. In this work, based on the measurement of near-infrared (NIR) spectroscopy and mid-infrared (MIR) spectra of strawberry powered, good classification results of 100.00% correct rates to distinguish whether the strawberry powder was made from freshly available or stored fruit was obtained. Furthermore, partial least squares regression and least squares support vector machines (LS-SVM) models were established based on NIR, MIR, and combination of NIR and MIR data with full variables or optimal variables of strawberry powder to predict the storage days of strawberries that produced the powder. Optimal variables were selected by successive projections algorithm (SPA), uninformation variable elimination, and competitive adaptive reweighted sampling, respectively. The best model was determined as the SPA-LS-SVM model based on MIR spectra, which had the residual prediction deviation (RPD) value of 11.198 and the absolute difference between root-mean-square error of calibration and prediction (AB_RMSE) value of 0.505. The results of this work confirmed the feasibility of using NIR and MIR spectroscopic techniques for rapid identification of strawberry powder made from freshly available and stored strawberry.

The rapid and non-destructive detection of mechanical damage to fruit during postharvest supply chains is important for monitoring fruit deterioration in time and optimizing freshness preservation and packaging strategies. As fruit is usually packed during supply chain operations, it is difficult to detect whether it has suffered mechanical damage by visual observation and spectral imaging technologies. In this study, based on the volatile substances (VOCs) in yellow peaches, the electronic nose (e-nose) technology was applied to non-destructively predict the levels of compression damage in yellow peaches, discriminate the damaged fruit and predict the time after the damage. A comparison of the models, established based on the samples at different times after damage, was also carried out. The results show that, at 24 h after damage, the correct answer rate for identifying the damaged fruit was 93.33%, and the residual predictive deviation in predicting the levels of compression damage and the time after the damage, was 2.139 and 2.114, respectively. The results of e-nose and gas chromatography-mass spectrophotometry (GC–MS) showed that the VOCs changed after being compressed—this was the basis of the e-nose detection. Therefore, the e-nose is a promising candidate for the detection of compression damage in yellow peach.

The burial dissolution of carbonate rocks has long been an interesting topic of reservoir geologists. Integrated with geological studies and reactive transport modeling, this study investigated the Cambrian dolomites that were buried at depths up to 8408 m and still preserved a large amount of unfilled dissolution vugs from the borehole TS1 in the northern Tarim Basin. Studies indicate that these vugs were formed in association with fault-channeled hydrothermal fluids from greater depth through “retrograde dissolution” as the fluid temperature dropped during upward migration. The reactive transport modeling results suggest an important control of the vertical permeability of wall-rock on fluid and temperature patterns which, in turn, would control the spatial distribution of dissolving-originated porosity. The hydrothermal dissolution mainly occurred in dolomite wall-rocks with higher vertical permeability (extensive development of tensional fractures and connected pore spaces), producing additional dissolved porosity there during deep burial. This study implicates the importance of multidisciplinary approaches for understanding the burial/hydrothermal dissolution of dolomite rocks and predicting favourable deep/ultradeep carbonate reservoirs.