Fingerprint Profiling of Glycans on Extracellular Vesicles via Lectin-Induced Aggregation Strategy for Precise Cancer Diagnostics.

Extracellular vesicles (EVs) harbor abundant glycans that mediate various functions, such as intercellular communication and disease advancement, which play significant roles in disease progression. However, the presence of EV heterogeneity in body fluids and the complex nature of the glycan structures have posed challenges for the detection of EV glycans. In this study, we provide a streamlined method integrated, membrane-specific separation with lectin-induced aggregation strategy (MESSAGE), for multiplexed profiling of EV glycans. By leveraging a rationally designed lectin-induced aggregation strategy, the expression of EV glycans is converted to size-based signals. With the assistance learning machine algorithms, the MESSAGE strategy with high sensitivity, specificity, and simplicity can be used for early cancer diagnosis and classification, as well as monitoring cancer metastasis via 20 µL plasma sample within 2 h. Furthermore, our platform holds promise for advancing the field of EV-based liquid biopsy for clinical applications, opening new possibilities for the profiling of EV glycan signatures in various disease states.

Preoperative Structural Risk Factors for Glaucoma After Penetrating Keratoplasty for Congenital Corneal Opacity: An Observational Study.

INTRODUCTION: Post-keratoplasty glaucoma (PKG) is a major complication following penetrating keratoplasty (PKP) for congenital corneal opacity (CCO). This study aims to assess the preoperative structural risk factors for PKG following PKP for CCO using ultrasound biomicroscopy (UBM). METHODS: Pediatric patients with CCO who underwent preoperative UBM and primary PKP were enrolled. Patients with anterior segment operation history or with a follow-up duration less than 12 months were excluded. The structural features of the anterior segment including central corneal thickness, anterior chamber depth, angle closure range (ACR), anterior synechia range, maximum iridocorneal adhesion length, abnormal iridocorneal synechia, and lens anomalies were identified on UBM images. The medical histories were reviewed to identify clinical features. The incidence of PKG was assessed to determine significant structural and clinical risk factors. RESULTS: Fifty-one eyes of 51 pediatric patients with CCO were included. The median age at surgery was 8.0 months, and the mean follow-up duration was 33 ± 9 months. Eleven (21.6%) eyes developed PKG. The main structural risk factors were abnormal iridocorneal synechia (P = 0.015), lens anomaly (P = 0.001), and larger ACR (P = 0.045). However, a larger range of normal anterior synechia without involvement of the angle was not a significant risk factor. Preoperative glaucoma (P < 0.001) and higher intraocular pressure (P = 0.015) were clinical risk factors. A shallow anterior chamber was a unique risk factor for sclerocornea (P = 0.019). CONCLUSIONS: Detailed preoperative examination of iridocorneal synechia, lens, and angle closure using UBM is critical for PKG risk assessment, surgical prognosis evaluation, and postoperative management in patients with CCO.

Neuroprotective effects of ulinastatin on Escherichia coli meningitis rats through inhibiting PKCα phosphorylation and reducing zonula occludens-1 degradation.

Ulinastatin, a broad-spectrum inflammatory inhibitor widely employed in the management of severe pancreatitis and sepsis, has not been extensively investigated for its therapeutic potential in bacterial meningitis. This study aims to assess the neuroprotective effects of ulinastatin on bacterial meningitis and elucidate its underlying mechanism. The rat model of bacterial meningitis was established by intracerebral injection of Escherichia coli. 3-week-old SD rats were randomly divided into 5 groups with 8 rats in each group, including control group, E.coli group, E.coli + UTI group (ulinastatin 50000IU/kg), E.coli + UTI + PMA group (ulinastatin 50000IU/kg + PMA 200 ug/kg), and E.coli + PMA group(PMA 200 ug/kg). Behavioral changes were assessed by Loeffler neurobehavioral score. Histomorphologic changes and apoptosis were assessed by hematoxylin and eosin staining, Nissl staining and TUNEL staining. Immunohistochemistry and immunofluorescence and western blotting were used to detect the expression levels of zonula occludens-1 (ZO-1) and phosphorylation protein kinase C (PKCα).It was found that ulinastatin treatment in Escherichia coli meningitis rats improved neurological function, alleviated meningeal inflammatory infiltration, reduced neuronal death, promoted the integrity of the blood-brain barrier structure. Moreover, phorbol myristate acetate (PMA, a protein kinase C activator), blocked the effective action of ulinastatin. These findings suggest that ulinastatin had neuroprotective effects on bacterial meningitis by inhibiting PKCα phosphorylation and reducing ZO-1 degradation, demonstrating that ulinastatin may be a promising strategy in the treatment of bacterial meningitis.

Relationship between maternal postpartum depression, fatigue, sleep quality and infant growth: A cross-sectional study.

BACKGROUND: Current research separately analyzed the connection between postpartum depression, fatigue, sleep and infant development. However, depression, fatigue and sleep quality often coexisted as adverse symptoms in postpartum women and influenced infant development together. This study explored the maternal postpartum symptoms on infant growth. METHODS: Our study included 224 pairs of singleton full-term mothers and their infants who underwent routine pediatric outpatient clinics. Latent profile analysis was applied to identify the latent classes based on mothers' postpartum depression, fatigue and sleep profile characteristics. We evaluated the maternal adverse symptoms and infant development using multivariable logistic regressions. RESULTS: Totally, 224 pairs of eligible mothers (28.85 ± 4.43 years) and infants (30.93 ± 3.26 days) participated in this study. Latent profile analysis identified 3 latent groups: mild (58.04%), moderate (34.37%), and severe (7.59%) postpartum adverse symptoms. Postpartum adverse symptoms were associated with delayed development in the baby's motor level (χ2 = 6.572, p = .037) and weight-for-length (χ2 = 9.652, p = .008). After controlling for mother and infant related factors, postpartum adverse symptoms remained a risk factor for infant motor level (odds ratio [OR]: 4.35; 95% confidence interval [CI]: 1.25-15.08) and weight-for-length (OR: 5.53; 95% CI: 1.55-19.74). CONCLUSIONS: Maternal postpartum depression, fatigue and sleep quality are associated with infant development. Clinically, mothers with these symptoms should be intervened timely to avoid the aggravation of maternal symptoms, which affect baby's development.

Diuretic Treatment in Heart Failure: A Practical Guide for Clinicians.

Congestion and fluid retention are the hallmarks of decompensated heart failure and the major reason for the hospitalization of patients with heart failure. Diuretics have been used in heart failure for decades, and they remain the backbone of the contemporary management of heart failure. Loop diuretics is the preferred diuretic, and it has been given a class I recommendation by clinical guidelines for the relief of congestion symptoms. Although loop diuretics have been used virtually among all patients with acute decompensated heart failure, there is still very limited clinical evidence to guide the optimized diuretics use. This is a sharp contrast to the rapidly growing evidence of the rest of the guideline-directed medical therapy of heart failure and calls for further studies. The loop diuretics possess a unique pharmacology and pharmacokinetics that lay the ground for different strategies to increase diuretic efficiency. However, many of these approaches have not been evaluated in randomized clinical trials. In recent years, a stepped and protocolized diuretics dosing has been suggested to have superior benefits over an individual clinician-based strategy. Diuretic resistance has been a major challenge to decongestion therapy for patients with heart failure and is associated with a poor clinical prognosis. Recently, therapy options have emerged to help overcome diuretic resistance to loop diuretics and have been evaluated in randomized clinical trials. In this review, we aim to provide a comprehensive review of the pharmacology and clinical use of loop diuretics in the context of heart failure, with attention to its side effects, and adjuncts, as well as the challenges and future direction.

The IGF2BP3/Notch/Jag1 pathway: A key regulator of hepatic stellate cell ferroptosis in liver fibrosis.

INTRODUCTION: Liver fibrosis is primarily driven by the activation of hepatic stellate cells (HSCs), which involves various epigenetic modifications. OBJECTIVES: N6-methyladenosine (m6A), the most prevalent RNA modification in eukaryotic cells, influences numerous physiological and pathological processes. Nevertheless, the role of insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3), a reader gene mediating m6A modifications, in liver fibrosis remains unclear. METHODS AND RESULTS: This study demonstrated that IGF2BP3 knockout reduces liver fibrosis by promoting HSC ferroptosis (FPT) and inactivating HSCs. Multi-omics analysis revealed that HSC-specific IGF2BP3 knockout decreased m6A content in Jagged1 (Jag1), a key component of the Notch signalling pathway. Furthermore, IGF2BP3 deficiency significantly reduced the expression of hairy and enhancer of split-1 (Hes1), a transcription factor in the Notch/Jag1 signalling pathway, with mRNA levels declining to 35%-62% and protein levels to 28%-35%. Additionally, it suppressed glutathione peroxidase 4 (GPX4) (decreased to approximately 31%-38%), a negative regulator of FPT, thereby facilitating HSC FPT progression and reducing profibrotic gene expression. CONCLUSION: These findings uncover a novel IGF2BP3/Notch/Jag1 signalling pathway involving HSC FPT, suggesting promising targets for ameliorating liver fibrosis. KEY POINTS/HIGHLIGHTS: IGF2BP3 deficiency inactivates Jag1 signalling. IGF2BP3 deficiency-mediated m6A modifications promote HSC ferroptosis. IGF2BP3 inhibition facilitates ferroptosis in HSCs via the Hes1/GPX4 axis. IGF2BP3 deficiency inactivates Jag1/Notch1/3/Hes1 signalling pathway inactivation, leading to the decrease in GPX4, which contributes to HSC ferroptosis.

Kobresia humilis via root-released flavonoids recruit Bacillus for promoted growth.

Alpine meadows, which are critical for biodiversity and ecosystem services, are increasingly degrading, necessitating effective restoration strategies. This study explored the mechanism by which Kobresia humilis, an alpine meadow-constructive species, modulates the rhizosphere microbiome via root exudates to enhance growth. Field investigations revealed that the plant height of K. humilis in a severely degraded (SD) alpine meadow was significantly higher than that in other K. humilis populations. Consequently, we analysed the differences between this plot and other K. humilis samples with different degrees of degradation to explore the reasons underlying the phenotypic differences in K. humilis. 16 S rRNA amplicon sequencing results showed that the SD plots were significantly enriched with more Bacillus, altering the composition of the rhizosphere microbial community of K. humilis. The collection and analysis of root exudates from various K. humilis locations revealed distinct differences. Procrustes analysis indicated a strong correlation between the root exudates and the rhizosphere microbiome composition of K. humilis. Model-based integration of metabolite observations, species abundance 2 (MIMOSA2), and Spearman's rank correlation coefficient analysis were used to identify the root exudates potentially related to the enrichment and recruitment of Bacillus. Bacillus from SD samples was isolated and screened, and the representative strain D334 was found to be differentially enriched compared to other samples. A series of in vitro experiments with the screened root exudates and strain D334 demonstrated that K. humilis could recruit Bacillus and promote its colonisation by releasing flavonoids, particularly baicalin. Additionally, K. humilis can release sucrose and riboflavin, which promote strain growth. Finally, soil microbiome transplantation experiments confirmed that different K. humilis phenotypes were closely related to the functions of the rhizosphere microbiome, especially in root morphological shaping. Moreover, the effects of Bacillus inoculation and the microbiome on the plant phenotypes were consistent. In summary, this study revealed a new mechanism by which K. humilis recruits rhizosphere growth-promoting bacteria and enhances soil nutrient utilisation, thereby promoting plant growth. These findings provide a theoretical basis for ecological restoration using soil microbial communities and clarify the relationship between plant metabolites and microbial community assembly.

Inhibiting miR-618 Promotes Keratinocytes Proliferation and Migration to Enhance Wound Healing in Mice.

The delay in wound healing caused by chronic wounds or pathological scars is a pressing issue in clinical practice, imposing significant economic and psychological burdens on patients. In particular, with the aging of the population and the increasing incidence of diseases such as diabetes, impaired wound healing is one of the growing health problems. MicroRNA (miRNA) plays a crucial role in wound healing and regulates various biological processes. Our results show that miR-618 was significantly upregulated during the inflammatory phase of wound healing.Subsequently, miR-618 promotes the secretion of pro-inflammatory cytokines and regulates the proliferation and migration of keratinocytes. Mechanistically, miR-618 binds to the target gene-Atp11b and inhibits the PI3K-Akt signaling pathway, inhibiting the epithelial-mesenchymal transition (EMT) of keratinocytes. In addition, the PI3K-Akt signaling pathway induces the enrichment of nuclear miR-618, and miR-618 binds to the promoter of Lin7a to regulate gene transcription. Intradermal injection of miR-618 antagomir around full-thickness wounds in peridermal mice effectively accelerates wound closure compared to control. In conclusion, miR-618 antagomir can be a potential therapeutic agent for wound healing.

Real-time analgesic efficacy and factors determining drug requirements of combined spinal-epidural analgesia for labor: a prospective cohort study.

PURPOSE: Combined spinal-epidural analgesia (CSEA) is effective but not sufficient for labor pain. This study was conducted to assess the real-time analgesic efficacy, side effects of anesthetic drug dosage, and maternal satisfaction in labor to provide reference for the optimization of labor analgesia. METHODS: This was a prospective, cohort, single-center study that included 3020 women who received CSEA for labor analgesia. The visual analogue scale (VAS) for labor pain, real-time anesthetic drug dosage, side effects, adverse labor outcomes, factors influencing average drug dosage, and maternal satisfaction with CSEA were assessed. RESULTS: Overall, the VAS labor pain score was lowest at the first hour after the anesthesia was given. After 4 h for primiparas and 3 h for multiparas, the VAS score was greater than 3 but the anesthetic drug dosage did not reach the maximum allowed dosage at the same time. The average anesthetic drug dosage was positively correlated with fever, urinary retention, uterine atony, prolonged active phase, prolonged second stage, assisted vaginal delivery, and postpartum hemorrhage. The average anesthetic drug dosage was the highest in women ≤ 20 years old, those with a body mass index (BMI) ≥ 24.9 kg/m2, and those with a primary or secondary education level. CONCLUSION: Appropriate age guidance and emphasis on education of labor analgesia, weight management during pregnancy, and real-time anesthetic dosage adjustment during labor based on VAS pain score may have positive effects on the satisfaction of labor analgesia. CLINICAL TRIAL NUMBER AND REGISTRY: Clinicaltrials.gov (ChiCTR2100051809).

Development and initial validation of the contemporary Chinese Familism Scale.

OBJECTIVES: Familism is a core ideology in Chinese society, yet it has been understudied in this cultural context, potentially attributed to the lack of quantifiable measures. This study sought to develop a reliable and valid scale, the Contemporary Chinese Familism Scale (CCFS), to assess Chinese familism and analyze its structural and psychological characteristics in contemporary China. METHOD: The scale development and validation process comprised four studies: in Study 1, literature review, qualitative interviews, and item evaluations by experts were conducted to develop the initial item pool for the CCFS; in Studies 2 and 3, item analysis, exploratory and confirmatory factor analyses, competing model comparisons, and measurement invariance tests were conducted to examine the structure underlying familism (N1 = 958, Mage = 25.4 years; N2 = 570, Mage = 32.01 years); in Study 4, reliability and validity assessments were conducted to further explore the psychometric properties of the final 27-item CCFS using three samples (N2 = 570, Mage = 32.01 years; N3 = 710, Mage = 22.37 years; N4 = 932, Mage = 40.98 years). RESULT: A bifactor structure with one general factor and five specific factors (Connection and Closeness, Offspring and Lineage, Honor and Reference, Harmony and Sacrifice, and Care and Help) demonstrated the best fit for the data and supported the multidimensionality of familism in contemporary China. Subsequent psychometric analyses provided initial evidence for the optimal psychometric properties of the CCFS. CONCLUSION: This study contributes to our understanding of the multifaceted nature of familism in contemporary China by developing a culturally sensitive scale on Chinese familism. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Management of patients with heart failure and chronic kidney disease.

Chronic kidney disease (CKD) and heart failure are often co-existing conditions due to a shared pathophysiological process involving neurohormonal activation and hemodynamic maladaptation. A wide range of pharmaceutical and interventional tools are available to patients with CKD, consisting of traditional ones with decades of experience and newer emerging therapies that are rapidly reshaping the landscape of medical care for this population. Management of patients with heart failure and CKD requires a stepwise approach based on renal function and the clinical phenotype of heart failure. This is often challenging due to altered drug pharmacokinetics interactions with various degrees of kidney function and frequent adverse effects from the therapy that lead to poor patient tolerance. Despite a great body of clinical evidence and guidelines that have offered various treatment options for patients with heart failure and CKD, respectively, patients with CKD are still underrepresented in heart failure clinical trials, especially for those with advanced CKD and end-stage renal disease (ESRD). Future studies are needed to better understand the generalizability of these therapeutic options among heart failures with different stages of CKD.

The Effect of Two Siderophore-Producing Bacillus Strains on the Growth Promotion of Perennial Ryegrass under Cadmium Stress.

Cadmium (Cd) is a highly toxic and cumulative environmental pollutant. Siderophores are heavy metal chelators with high affinity to heavy metals, such as Cd. Ryegrass (Lolium perenne L.) has a potential remediation capacity for soils contaminated by heavy metals. Consequently, using ryegrass alongside beneficial soil microorganisms that produce siderophores may be an effective means to remediate soils contaminated with Cd. In this study, the Bacillus strains WL1210 and CD303, which were previously isolated from the rhizospheres of Nitraria tangutorum in Wulan and Peganum harmala L. in Dachaidan, Qinghai, China, respectively, both arid and sandy environments, were evaluated for heavy metal pollution mitigation. Our quantitative analyses have discerned that the two bacterial strains possess commendable attributes of phosphorus (P) solubilization and potassium (K) dissolution, coupled with the capacity to produce phytohormones. To assess the heavy metal stress resilience of these strains, they were subjected to a cadmium concentration gradient, revealing their incremental growth despite cadmium presence, indicative of a pronounced tolerance threshold. The subsequent phylogenetic analysis, bolstered by robust genomic data from conserved housekeeping genes, including 16S rDNA, gyr B gene sequencing, as well as dnaK and recA, delineated a species-level phylogenetic tree, thereby confirming the strains as Bacillus atrophaeus. Additionally, we identified the types of iron-carrier-producing strains as catechol (WL1210) and carboxylic acid ferrophilin (CD303). A genomic analysis uncovered functional genes in strain CD303 associated with plant growth and iron carrier biosynthesis, such as fnr and iscA. Ryegrass seed germination assays, alongside morphological and physiological evaluations under diverse heavy metal stress, underscored the strains' potential to enhance ryegrass growth under high cadmium stress when treated with bacterial suspensions. This insight probes the strains' utility in leveraging alpine microbial resources and promoting ryegrass proliferation.

Depleting profibrotic macrophages using bioactivated in vivo assembly peptides ameliorates kidney fibrosis.

Managing renal fibrosis is challenging owing to the complex cell signaling redundancy in diseased kidneys. Renal fibrosis involves an immune response dominated by macrophages, which activates myofibroblasts in fibrotic niches. However, macrophages exhibit high heterogeneity, hindering their potential as therapeutic cell targets. Herein, we aimed to eliminate specific macrophage subsets that drive the profibrotic immune response in the kidney both temporally and spatially. We identified the major profibrotic macrophage subset (Fn1+Spp1+Arg1+) in the kidney and then constructed a 12-mer glycopeptide that was designated as bioactivated in vivo assembly PK (BIVA-PK) to deplete these cells. BIVA-PK specifically binds to and is internalized by profibrotic macrophages. By inducing macrophage cell death, BIVA-PK reshaped the renal microenvironment and suppressed profibrotic immune responses. The robust efficacy of BIVA-PK in ameliorating renal fibrosis and preserving kidney function highlights the value of targeting macrophage subsets as a potential therapy for patients with CKD.

A self-immobilizing near-infrared fluorogenic probe for in vivo imaging of fibroblast activation protein-α.

Fibroblast activation protein-α (FAP) plays a crucial role in various physiological and pathological processes, making it a key target for cancer diagnostics and therapeutics. However, in vivo detection of FAP activity with fluorogenic probes remains challenging due to the rapid diffusion and clearance of fluorescent products from the target. Herein, we developed a self-immobilizing near-infrared (NIR) fluorogenic probe, Hcy-CF2H-PG, by introducing a difluoromethyl group to FAP substrate-caged NIR fluorophore. Upon selective activation by FAP, the fluorescence of Hcy-CF2H-PG was triggered, followed by the covalent labelling of FAP. Hcy-CF2H-PG demonstrated significantly improved sensitivity, selectivity, and long-lasting labelling capacity for FAP both in vitro and in vivo, compared to that of non-immobilized probes. This represents a noteworthy advancement in FAP detection and cancer diagnostics within complex physiological systems.

A DNA-Modularized STING Agonist with Macrophage-Selectivity and Programmability for Enhanced Anti-Tumor Immunotherapy.

The activation of cyclic GMP-AMP (cGAMP) synthase (cGAS) and its adaptor, stimulator of interferon genes (STING), is known to reprogram the immunosuppressive tumor microenvironment for promoting antitumor immunity. To enhance the efficiency of cGAS-STING pathway activation, macrophage-selective uptake, and programmable cytosolic release are crucial for the delivery of STING agonists. However, existing polymer- or lipid-based delivery systems encounter difficulty in integrating multiple functions meanwhile maintaining precise control and simple procedures. Herein, inspired by cGAS being a natural DNA sensor, a modularized DNA nanodevice agonist (DNDA) is designed that enable macrophage-selective uptake and programmable activation of the cGAS-STING pathway through precise self-assembly. The resulting DNA nanodevice acts as both a nanocarrier and agonist. Upon local administration, it demonstrates the ability of macrophage-selective uptake, endosomal escape, and cytosolic release of the cGAS-recognizing DNA segment, leading to robust activation of the cGAS-STING pathway and enhanced antitumor efficacy. Moreover, DNDA elicits a synergistic therapeutic effect when combined with immune checkpoint blockade. The study broadens the application of DNA nanotechnology as an immune stimulator for cGAS-STING activation.

Incidence and Impact of Takotsubo Syndrome in Hospitalized Patients With COVID-19.

BACKGROUND: Takotsubo syndrome has been reported in patients with COVID-19, although minimal data are available. This investigation assessed the incidence and impact of takotsubo syndrome on patients hospitalized with COVID-19. METHODS: A retrospective cohort study was conducted using International Statistical Classification of Diseases, Tenth Revision, codes to identify patients with a primary diagnosis of COVID-19 with or without takotsubo syndrome in the National Inpatient Sample 2020 database. Outcomes between groups were compared after propensity score matching for patient and hospital demographics and comorbidities. RESULTS: A total of 211,448 patients with a primary diagnosis of COVID-19 were identified. Of these, 171 (0.08%) had a secondary diagnosis of takotsubo syndrome. Before matching, patients with COVID-19 and takotsubo syndrome, compared with patients without takotsubo syndrome, were older (68.95 vs 64.26 years; P < .001); more likely to be female (64.3% vs 47.2%; P < .001); and more likely to have anxiety (24.6% vs 12.8%; P < .001), depression (17.5% vs 11.4%; P = .02), and chronic obstructive pulmonary disease (24.6% vs 14.7%; P < .001). The takotsubo syndrome group had worse outcomes than the non-takotsubo syndrome group for death (30.4% vs 11.1%), cardiac arrest (7.6% vs 2.1%), cardiogenic shock (12.9% vs 0.4%), length of hospital stay (10.7 vs 7.5 days), and total charges ($152,685 vs $78,468) (all P < .001). After matching and compared with the non-takotsubo syndrome group (n = 508), the takotsubo syndrome group (n = 170) had a higher incidence of inpatient mortality (30% vs 14%; P < .001), cardiac arrest (7.6% vs 2.8%; P = .009), and cardiogenic shock (12.4% vs 0.4%; P < .001); a longer hospital stay (10.7 vs 7.6 days; P < .001); and higher total charges ($152,943 vs $79,523; P < .001). CONCLUSION: Takotsubo syndrome is a rare but severe in-hospital complication in patients with COVID-19.

LINC00606 promotes glioblastoma progression through sponge miR-486-3p and interaction with ATP11B.

BACKGROUND: LncRNAs regulate tumorigenesis and development in a variety of cancers. We substantiate for the first time that LINC00606 is considerably expressed in glioblastoma (GBM) patient specimens and is linked with adverse prognosis. This suggests that LINC00606 may have the potential to regulate glioma genesis and progression, and that the biological functions and molecular mechanisms of LINC00606 in GBM remain largely unknown. METHODS: The expression of LINC00606 and ATP11B in glioma and normal brain tissues was evaluated by qPCR, and the biological functions of the LINC00606/miR-486-3p/TCF12/ATP11B axis in GBM were verified through a series of in vitro and in vivo experiments. The molecular mechanism of LINC00606 was elucidated by immunoblotting, FISH, RNA pulldown, CHIP-qPCR, and a dual-luciferase reporter assay. RESULTS: We demonstrated that LINC00606 promotes glioma cell proliferation, clonal expansion and migration, while reducing apoptosis levels. Mechanistically, on the one hand, LINC00606 can sponge miR-486-3p; the target gene TCF12 of miR-486-3p affects the transcriptional initiation of LINC00606, PTEN and KLLN. On the other hand, it can also regulate the PI3K/AKT signaling pathway to mediate glioma cell proliferation, migration and apoptosis by binding to ATP11B protein. CONCLUSIONS: Overall, the LINC00606/miR-486-3p/TCF12/ATP11B axis is involved in the regulation of GBM progression and plays a role in tumor regulation at transcriptional and post-transcriptional levels primarily through LINC00606 sponging miR-486-3p and targeted binding to ATP11B. Therefore, our research on the regulatory network LINC00606 could be a novel therapeutic strategy for the treatment of GBM.

Drought stress tolerance and metabolomics of Medicago sativa induced by Bacillus amyloliquefaciens DGL1.

Introduction: This study used Bacillus amyloliquefaciens DGL1 isolated from the arid sandy land of the Qinghai-Tibetan Plateau as the research strain and investigated the effects of DGL1 on the biomass, physiology, and metabolites of Medicago sativa under different intensities of drought stress to provide a high-quality bacterial source and a theoretical basis for the research and development of biological fertilizer suitable for arid areas. Methods: The exopolysaccharides (EPS), 1-Aminocyclopropane-1-carboxylate deaminase (ACC), and phosphorus solubilizing capacity of DGL1 were determined. The effects of a DGL1 suspension on alfalfa biomass, physiological indexes, degree of peroxidation of cell membranes, and activity of antioxidant enzymes were determined after irrigating roots under drought stress. The effects on soil physicochemical properties were also evaluated, and metabolomics analysis was performed to explore the effect of DGL1 on the metabolites of alfalfa under drought stress. Results: Strain DGL1 produced extracellular polysaccharide EPS and ACC deaminase and was capable of phosphorus solubilization. Treatment with DGL1 increased the biomass of alfalfa under different degrees of drought stress, significantly increased the activities of alfalfa antioxidant enzymes Super Oxide Dismutase (SOD), Peroxidase (POD), and catalase (CAT), reduced the content of MDA and H2O2, and increased the content of quick-acting phosphorus, quick-acting potassium, ammonium nitrogen, and nitrate nitrogen in the soil, thus improving soil fertility. Through metabolomics analysis, DGL1 was shown to affect amino acid metabolic pathways, such as arginine, leucine, glutamate, and tyrosine, as well as the levels of energy-providing polysaccharides and lipids, in alfalfa under 15% PEG-6000 drought stress, enhancing alfalfa's capacity to resist drought stress. Discussion: Strain DGL1 enhances the drought suitability of alfalfa and has the potential for dryland development as a biological agent.