GIMAP5 deficiency reveals a mammalian ceramide-driven longevity assurance pathway.

Preserving cells in a functional, non-senescent state is a major goal for extending human healthspans. Model organisms reveal that longevity and senescence are genetically controlled, but how genes control longevity in different mammalian tissues is unknown. Here, we report a new human genetic disease that causes cell senescence, liver and immune dysfunction, and early mortality that results from deficiency of GIMAP5, an evolutionarily conserved GTPase selectively expressed in lymphocytes and endothelial cells. We show that GIMAP5 restricts the pathological accumulation of long-chain ceramides (CERs), thereby regulating longevity. GIMAP5 controls CER abundance by interacting with protein kinase CK2 (CK2), attenuating its ability to activate CER synthases. Inhibition of CK2 and CER synthase rescues GIMAP5-deficient T cells by preventing CER overaccumulation and cell deterioration. Thus, GIMAP5 controls longevity assurance pathways crucial for immune function and healthspan in mammals.

Structural basis for TNIP1 binding to FIP200 during mitophagy.

TNIP1 has been increasingly recognized as a security check to finely adjust the rate of mitophagy by disrupting the recycling of the Unc-51-like kinase complex during autophagosome formation. Through tank-binding kinase 1-mediated phosphorylation of the TNIP1 FIP200 interacting region (FIR) motif, the binding affinity of TNIP1 for FIP200, a component of the Unc-51-like kinase complex, is enhanced, allowing TNIP1 to outcompete autophagy receptors. Consequently, FIP200 is released from the autophagosome, facilitating further autophagosome expansion. However, the molecular basis by which FIP200 utilizes its claw domain to distinguish the phosphorylation status of residues in the TNIP1 FIR motif for recognition is not well understood. Here, we elucidated multiple crystal structures of the complex formed by the FIP200 claw domain and various phosphorylated TNIP1 FIR peptides. Structural and isothermal titration calorimetry analyses identified the crucial residues in the FIP200 claw domain responsible for the specific recognition of phosphorylated TNIP1 FIR peptides. Additionally, utilizing structural comparison and molecular dynamics simulation data, we demonstrated that the C-terminal tail of TNIP1 peptide affected its binding to the FIP200 claw domain. Moreover, the phosphorylation of TNIP1 Ser123 enabled the peptide to effectively compete with the peptide p-CCPG1 (the FIR motif of the autophagy receptor CCPG1) for binding with the FIP200 claw domain. Overall, our work provides a comprehensive understanding of the specific recognition of phosphorylated TNIP1 by the FIP200 claw domain, marking an initial step toward fully understanding the molecular mechanism underlying the TNIP1-dependent inhibition of mitophagy.

Granzyme B degrades extracellular matrix and promotes inflammation and choroidal neovascularization.

Age-related macular degeneration (AMD) is a common retinal neurodegenerative disease among the elderly. Neovascular AMD (nAMD), a leading cause of AMD-related blindness, involves choroidal neovascularization (CNV), which can be suppressed by anti-angiogenic treatments. However, current CNV treatments do not work in all nAMD patients. Here we investigate a novel target for AMD. Granzyme B (GzmB) is a serine protease that promotes aging, chronic inflammation and vascular permeability through the degradation of the extracellular matrix (ECM) and tight junctions. Extracellular GzmB is increased in retina pigment epithelium (RPE) and mast cells in the choroid of the healthy aging outer retina. It is further increased in donor eyes exhibiting features of nAMD and CNV. Here, we show in RPE-choroidal explant cultures that exogenous GzmB degrades the RPE-choroid ECM, promotes retinal/choroidal inflammation and angiogenesis while diminishing anti-angiogenic factor, thrombospondin-1 (TSP-1). The pharmacological inhibition of either GzmB or mast-cell degranulation significantly reduces choroidal angiogenesis. In line with our in vitro data, GzmB-deficiency reduces the extent of laser-induced CNV lesions and the age-related deterioration of electroretinogram (ERG) responses in mice. These findings suggest that targeting GzmB, a serine protease with no known endogenous inhibitors, may be a potential novel therapeutic approach to suppress CNV in nAMD.

IGF2BP3 promotes glutamine metabolism of endometriosis by interacting with UCA1 to enhances the mRNA stability of GLS1.

BACKGROUND: Insulin like growth factor II mRNA binding protein 3 (IGF2BP3) has been implicated in numerous inflammatory and cancerous conditions. However, its precise molecular mechanisms in endometriosis (EMs) remains unclear. The aim of this study is to examine the influence of IGF2BP3 on the occurrence and progression of EMs and to elucidate its underlying molecular mechanism. METHODS: Efects of IGF2BP3 on endometriosis were confrmed in vitro and in vivo. Based on bioinformatics analysis, RNA immunoprecipitation (RIP), RNA pull-down assays and Fluorescent in situ hybridization (FISH) were used to show the association between IGF2BP3 and UCA1. Single-cell spatial transcriptomics analysis shows the expression distribution of glutaminase 1 (GLS1) mRNA in EMs. Study the effect on glutamine metabolism after ectopic endometriotic stromal cells (eESCs) were transfected with Sh-IGF2BP3 and Sh-UCA1 lentivirus. RESULTS: Immunohistochemical staining have revealed that IGF2BP3 was upregulated in ectopic endometriotic lesions (EC) compared to normal endometrial tissues (EN). The proliferation and migration ability of eESCs were greatly reduced by downregulating IGF2BP3. Additionally, IGF2BP3 has been observed to interact with urothelial carcinoma associated 1 (UCA1), leading to increased stability of GLS1 mRNA and subsequently enhancing glutamine metabolism. Results also demonstrated that IGF2BP3 directly interacts with the 3' UTR region of GLS1 mRNA, influencing its expression and stability. Furthermore, UCA1 was able to bind with c-MYC protein, stabilizing c-MYC mRNA and consequently enhancing GLS1 expression through transcriptional promotion. CONCLUSION: These discoveries underscored the critical involvement of IGF2BP3 in the elevation and stability of GLS1 mRNA in the context of glutamine metabolism by interacting with UCA1 in EMs. The implications of our study extended to the identification of possible therapeutic targets for individuals with EMs.

Longitudinal Follow-Up of Fibrosis-4 in Patients at Risk of Metabolic Dysfunction-Associated Steatotic Liver Disease Receiving Low-Dose Methotrexate Treatment.

Several noninvasive liver fibrosis tests have been developed and appear to predict the severity of fibrosis, possibly replacing invasive liver biopsy as a monitoring tool.1 The fibrosis-4 (FIB-4) score originally was proposed to help assess liver fibrosis in patients with human immunodeficiency virus and hepatitis C virus co-infection.1 FIB-4 has been used widely to monitor the severity of liver fibrosis, especially in patients with nonalcoholic fatty liver disease,2 now termed metabolic dysfunction-associated steatotic liver disease (MASLD).3.

F11R RNA trinucleotide over-edited by ADAR in gastric and colorectal cancers: Cross-cohort validation, gene expression regulation, and diagnostic significance.

The F11 receptor (F11R) gene encoding junctional adhesion molecule A has been associated with gastric cancer (GC) and colorectal cancer (CRC), in which its role and regulation remain to be further elucidated. Recently F11R was also identified as a potential target of adenosine-to-inosine (A-to-I) mediated by the adenosine deaminases acting on RNA (ADARs). Herein, using RNA-Seq and experimental validation, our current study revealed an F11R RNA trinucleotide over-edited by ADAR, with its regulation of gene expression and clinical significance in four GC and three CRC cohorts. Our results found an over-edited AAA trinucleotide in an AluSg located in the F11R 3'-untranslated region (3'-UTR), which showed editing levels correlated with elevated ADAR expression across all GC and CRC cohorts in our study. Overexpression and knockdown of ADAR in GC and CRC cells, followed by RNA-Seq and Sanger sequencing, confirmed the ADAR-mediated F11R 3'-UTR trinucleotide editing, which potentially disrupted an RBM45 binding site identified by crosslinking immunoprecipitation sequencing (CLIP-seq) and regulated F11R expression in luciferase reporter assays. Moreover, the F11R trinucleotide editing showed promising predictive performance for diagnosing GC and CRC across GC and CRC cohorts. Our findings thus highlight both the potential biological and clinical significance of an ADAR-edited F11R trinucleotide in GC and CRC, providing new insights into its application as a novel diagnostic biomarker for both cancers.

Bio-Sprayed/Threaded Microalgae Remain Viable and Indistinguishable from Controls.

Microalgae are increasingly playing a significant role in many areas of research and development. Recent studies have demonstrated their ability to aid wound healing by their ability to generate oxygen, aiding the healing process. Bearing this in mind, the capability to spray/spin deposit microalgae in suspension (solution) or compartmentalize living microalgae within architectures such as fibers/scaffolds and beads, would have significance as healing mechanisms for addressing a wide range of wounds. Reconstructing microalgae-bearing architectures as either scaffolds or beads could be generated via electric field (bio-electrospraying and cell electrospinning) and non-electric field (aerodynamically assisted bio-jetting/threading) driven technologies. However, before studying the biomechanical properties of the generated living architectures, the microalgae exposed to these techniques must be interrogated from a molecular level upward first, to establish these techniques, have no negative effects brought on the processed microalgae. Therefore these studies, demonstrate the ability of both these jetting and threading technologies to directly handle living microalgae, in suspension or within a polymeric suspension, safely, and form algae-bearing architectures such as beads and fibers/scaffolds.

Oral-gut microbial transmission promotes diabetic coronary heart disease.

BACKGROUND: Diabetes is a predominant driver of coronary artery disease worldwide. This study aims to unravel the distinct characteristics of oral and gut microbiota in diabetic coronary heart disease (DCHD). Simultaneously, we aim to establish a causal link between the diabetes-driven oral-gut microbiota axis and increased susceptibility to diabetic myocardial ischemia-reperfusion injury (MIRI). METHODS: We comprehensively investigated the microbial landscape in the oral and gut microbiota in DCHD using a discovery cohort (n = 183) and a validation chohort (n = 68). Systematically obtained oral (tongue-coating) and fecal specimens were subjected to metagenomic sequencing and qPCR analysis, respectively, to holistically characterize the microbial consortia. Next, we induced diabetic MIRI by administering streptozotocin to C57BL/6 mice and subsequently investigated the potential mechanisms of the oral-gut microbiota axis through antibiotic pre-treatment followed by gavage with specific bacterial strains (Fusobacterium nucleatum or fecal microbiota from DCHD patients) to C57BL/6 mice. RESULTS: Specific microbial signatures such as oral Fusobacterium nucleatum and gut Lactobacillus, Eubacterium, and Roseburia faecis, were identified as potential microbial biomarkers in DCHD. We further validated that oral Fusobacterium nucleatum and gut Lactobacillus are increased in DCHD patients, with a positive correlation between the two. Experimental evidence revealed that in hyperglycemic mice, augmented Fusobacterium nucleatum levels in the oral cavity were accompanied by an imbalance in the oral-gut axis, characterized by an increased coexistence of Fusobacterium nucleatum and Lactobacillus, along with elevated cardiac miRNA-21 and a greater extent of myocardial damage indicated by TTC, HE, TUNEL staining, all of which contributed to exacerbated MIRI. CONCLUSION: Our findings not only uncover dysregulation of the oral-gut microbiota axis in diabetes patients but also highlight the pivotal intermediary role of the increased abundance of oral F. nucleatum and gut Lactobacillus in exacerbating MIRI. Targeting the oral-gut microbiota axis emerges as a potent strategy for preventing and treating DCHD. Oral-gut microbial transmission constitutes an intermediate mechanism by which diabetes influences myocardial injury, offering new insights into preventing acute events in diabetic patients with coronary heart disease.

Study on the immune-enhancing and inhabiting transmissible gastroenteritis virus effects of polysaccharides from Cimicifuga rhizoma.

Cimicifugae rhizoma is a traditional Chinese herbal medicine in China, and modern pharmacological research showed that it has obvious antiviral activity. Many polysaccharides have been proved to have immune enhancement and antiviral activity, but there are few studies on the biological activity of Cimicifuga rhizoma polysaccharide (CRP). The aim was to explore the character of CRP and its effects on improving immune activity and inhibiting transmissible gastroenteritis virus (TGEV). The monosaccharide composition, molecular weight, fourier transform infrared spectra and electron microscopy analysis of CRP was measured. The effect of CRP on immune activity in lymphocytes and RAW264.7 cells were studied by colorimetry, FITC-OVA fluorescent staining and ELISA. The effect of CRP on TGEV-infected PK-15 cells was determined using Real-time PCR, Hoechst fluorescence staining, trypan blue staining, acridine orange staining, Annexin V-FITC/PI fluorescent staining, DCFH-DA loading probe, and JC-1 staining. Network pharmacology was used to predict the targets of CRP in enhancing immunity and anti-TGEV, and molecular docking was used to further analyze the binding mode between CPR and core targets. The results showed that CRP was mainly composed of glucose and galactose, and its molecular weight was 64.28 kDa. The content of iNOS and NO in CRP group were significantly higher than the control group. CRP (125 and 62.5 µg/mL) could significantly enhance the phagocytic capacity of RAW264.7 cells, and imprive the content of IL-1ß content compared with control group. 250 µg/mL of CRP possessed the significant inhibitory effect on TGEV, which could significantly reduce the apoptosis compared to TGVE group and inhibit the decrease in mitochondrial membrane potential compared to TGVE group. The mRNA expression of TGEV N gene in CRP groups was significantly lower than TGEV group. PPI showed that the core targets of immune-enhancing were AKT1, MMP9, HSP90AA1, etc., and the core targets of TGE were CASP3, MMP9, EGFR, etc. Molecular docking show that CRP has binding potential with target. These results indicated that CRP possessed the better immune enhancement effect and anti-TGEV activity.

Photocatalyst Au@Ni-MOFs with Different Plasmonic Coverages for Improved Hydrogen Evolution from Water.

Plasmonic materials are fundamental photosensitizer materials for photocatalytic reactions. Various structures, including core-shell types, satellite types, and distribution types, have been designed and prepared for the optimization of photocatalytic reactions. However, understanding the profound enhancement mechanism of various structures is still challenging. Thus, the plasmonic coverage is considered to be an index for analyzing the influence mechanism. Here, Au@Ni-MOF core-shell flower sphere-like photocatalysts are prepared, and the size of the flower sphere can be precisely regulated by varying the amount of Au. Thus, different plasmonic coverages are realized through the tuning of spheres of different sizes. The high plasmonic coverage of catalysts can enhance visible light absorption, facilitate the generation of photogenerated electron-hole pairs, and shorten the photogenerated carrier transport distance. Moreover, the exponential relationship between the photocatalytic hydrogen production performance and the plasmonic coverage can also be used as a guide for material design. As a result, a photocatalytic hydrogen production rate of 3389 µmol·g-1·h-1 is achieved in the Au@Ni-MOF sample with high plasmonic coverage, which will advance the plasmonic application in photocatalytic reactions.

Exosomes regulate doxorubicin resistance in breast cancer via miR-34a-5p/NOTCH1.

Breast cancer (BRCA) is the most common cancer among women. Adriamycin (ADR), also known as doxorubicin (Dox), is a commonly used chemotherapeutic agent for BRCA patients, however, the susceptibility of tumor cells to develop resistance to Dox has severely limited its clinical use. One new promising therapeutic target for breast cancer patients is exosomes. The objective of this study was to investigate the role of exosomes in regulating Dox resistance in BRCA. In this study, the exosomes from both types of cells were extracted by differential centrifugation. The effect of exosomes on drug resistance was assessed by laser confocal microscopy, MTT assay, and qRT-PCR. The miRNA was transfected into cells using Lipofectamine 2000, which was then evaluated for downstream genes and changes in drug resistance. Exosomes from MCF-7 cells (MCF-7/exo) and MCF-7/ADR cells (ADR/exo) were effectively extracted in this study. The ADR/exo was able to endocytose MCF-7 cells and make them considerably more resistant to Dox. Moreover, we observed a significant difference in miR-34a-5p expression in MCF-7/ADR and ADR/exo compared to MCF-7 and MCF-7/exo. Among the miR-34a-5p target genes, NOTCH1 displayed a clear change with a negative correlation. In addition, when miR-34a-5p expression was elevated in MCF-7/ADR cells, the expression of miR-34a-5p in ADR/exo was also enhanced alongside NOTCH1, implying that exosomes may carry miRNA into and out of cells and perform their function. In conclusion, exosomes can influence Dox resistance in breast cancer cells by regulating miR-34a-5p/NOTCH1. These findings provide novel insights for research into the causes of tumor resistance and the enhancement of chemotherapy efficacy in breast cancer.

The role of strigolactones in resistance to environmental stress in plants.

Abiotic stress impairs plant growth and development, thereby causing low yield and inferior quality of crops. Increasing studies reported that strigolactones (SL) are plant hormones that enhance plant stress resistance by regulating plant physiological processes and gene expressions. In this review, we introduce the response and regulatory role of SL in salt, drought, light, heat, cold and cadmium stresses in plants. This review also discusses how SL alleviate the damage of abiotic stress in plants, furthermore, introducing the mechanisms of SL enhancing plant stress resistance at the genetic level. Under abiotic stress, the exogenous SL analog GR24 can induce the biosynthesis of SL in plants, and endogenous SL can alleviate the damage caused by abiotic stress. SL enhanced the stress resistance of plants by protecting photosynthesis, enhancing the antioxidant capacity of plants and promoting the symbiosis between plants and arbuscular mycorrhiza (AM). SL interact with abscisic acid (ABA), salicylic acid (SA), auxin, cytokinin (CK), jasmonic acid (JA), hydrogen peroxide (H2O2) and other signal molecules to jointly regulate plant stress resistance. Lastly, both the importance of SL and their challenges for future work are outlined in order to further elucidate the specific mechanisms underlying the roles of SL in plant responses to abiotic stress.

Orexin B protects dopaminergic neurons from 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity associated with reduced extracellular signal-regulated kinase phosphorylation.

BACKGROUND: The loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc) is a major pathological hallmark of Parkinson's disease (PD). Orexin B (OXB) has been reported to promote the growth of DA neurons. However, the roles of OXB in the degeneration of DA neurons still remained not fully clear. METHODS: An in vivo PD model was constructed by administrating 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice. Pole test was performed to investigate the motor function of mice and the number of DA neurons was detected by immunofluorescence (IF). A PD cell model was established by treating SH-SY5Y cells with 1-methyl-4-phenylpyridinium (MPP+). OXB was added to the culture medium 2 h after MPP + treatment. Microscopic analysis was carried out to investigate the function of OXB in the cell model of PD 24 h after MPP + challenge. RNA-Seq analysis of the PD cell model was performed to explore the possible mechanisms. Western blot was used to detect the phosphorylation levels of extracellular signal-regulated kinase (ERK). RESULTS: OXB significantly decreased the DA neurons death caused by MPTP, alleviated MPP+-induced neurotoxicity in SH-SY5Y cells, and robustly enhanced the weight and motor ability of PD mice. Besides, RNA-Seq analysis demonstrated that the mitogen-activated protein kinase (MAPK) pathway was involved in the pathology of PD. Furthermore, MPP + led to increased levels of phosphorylation of ERK (p-ERK), OXB treatment significantly decreased the levels of p-ERK in MPP+-treated SH-SY5Y cells. CONCLUSIONS: This study demonstrated that OXB exerts a neuroprotective role associated with reduced ERK phosphorylation in the PD model. This suggests that OXB may have therapeutic potential for treatment of PD.

Morphology and location of thrombus and sludge in patients with non-valvular atrial fibrillation.

BACKGROUND: Stroke and thromboembolism in nonvalvular atrial fibrillation (NVAF) primarily arise from thrombi or sludge in the left atrial appendage (LAA). Comprehensive insight into the characteristics of these formations is essential for effective risk assessment and management. METHODS: We conducted a single-center retrospective observational of 176 consecutive NVAF patients with confirmed atrial/appendage thrombus or sludge determined by a pre-ablation transesophageal echocardiogram (TEE) from December 2017 to April 2019. We obtained clinical and echocardiographic characteristics, including left atrial appendage emptying velocity (LAAeV) and filling velocity (LAAfV). Data analysis focused on identifying the morphology and location of thrombus or sludge. Patients were divided into the solid thrombus and sludge groups, and the correlation between clinical and echocardiographic variables and thrombotic status was analyzed. RESULTS: Morphological classification: In total, thrombi were identified in 78 patients, including 71 (40.3%) mass and 7 (4.0%) lamellar, while sludge was noted in 98 (55.7%). Location classification: 92.3% (72/78) of patients had thrombus confined to the LAA; 3.8% (3/78) had both LA and LAA involvement; 2.7% (2/78) had LA, LAA and RAA extended into the RA, the remained 1.2%(1/78) was isolated to RAA. 98.0% (96/98) of patients had sludge confined to the LAA; the remaining 2.0% (2/98) were present in the atrial septal aneurysm, which protrusion of interatrial septum into the RA. The thrombus and sludge groups showed low LAAeV (19.43 ± 9.59 cm/s) or LAAfV (17.40 ± 10.09 cm/s). Only LA dimension ≥ 40 mm was independently associated with the thrombus state in the multivariable model. CONCLUSION: This cohort study identified rare thrombus morphology and systematically summarized the classification of thrombus morphology. The distribution of thrombus and sludge outside limited to LAA was updated, including bilateral atrial and appendage involvement and rare atrial septal aneurysm sludge. LAAeV and LAAfV were of limited value in distinguishing solid thrombus from sludge. CLINICAL TRIAL NUMBER: ChiCTR-OCH-13,003,729.

Involvement of energy and cell wall metabolisms in chilling tolerance improved by hydrogen sulfide in cold-stored tomato fruits.

KEY MESSAGE: Hydrogen sulfide improved cold resistance of tomato fruits by regulating energy metabolism and delaying cell wall degradation, thereby alleviating the damage of cold storage on fruits. Postharvest cold storage in tomato fruits extended shelf life but caused the appearance of chilling injury (CI), appeared by softness and spots on the surface of the fruits. These changes were linked closely with energy and cell wall metabolisms. Hydrogen sulfide (H2S), as the gaseous fresh-keeping regulator, was used in the present study to investigate the effects of H2S on energy and cell wall metabolisms in tomato fruits during cold storage. Fruits after harvest were fumigated with different concentrations (0, 0.5, 1, 1.5 mM) of sodium hydrosulfide (NaHS) solution as H2S honor for 24 h and stored at 4 °C for 25 days. The results showed that 1 and 1.5 mM NaHS solution fumigation promoted the accumulation of endogenous H2S, followed by the increase in L-cysteine desulfurase (LCD) and D-cysteine desulfurase (DCD) activities in fruits during cold storage. It was also found that 1 and 1.5 mM NaHS treatments improved H+-ATPase, Ca2+-ATPase, cytochrome C oxidase (CCO), and succinic dehydrogenase (SDH) activities. Moreover, the contents of cellulose and hemicellulose were increased by 1 and 1.5 mM NaHS, following down-regulated activities of cellulase (CL), pectin lyase (PL), α-mannosidase (α-man) and ß-Galactosidase (ß-Gal) and down-regulated expression of PL1, PL8, MAN4 and MAN7 genes. Thus, H2S alleviates CI led by cold storage in tomato fruits via regulating energy and cell wall metabolisms.

CircRNA (circ)_0007823 Contributes to Triple-Negative Breast Cancer Progression and Cisplatin Resistance via the miR-182-5p/FOXO1 Pathway.

Cisplatin (DDP) is used for the clinical management of triple-negative breast cancer (TNBC). However, the development of drug resistance limits its therapeutic efficacy. Circular RNAs (circRNAs) are known to be involved in tumor DDP resistance. In our previous study, we reported that circ_0007823 expression is downregulated and correlated with adverse prognosis in TNBC. However, its association with DDP resistance remains unclear. This study aimed to determine the role of circ_0007823 and miR-182-5p in DDP-resistant TNBC and explore the underlying mechanisms. First, expression profiles circ_0007823, microRNA (miR)-182-5p, and forkhead box O1 (FOXO1) in TNBC cells were determined. Additionally, biological characteristics of cells, including apoptosis, cell cycle, proliferation, and migration, were analyzed using various assays. Luciferase reporter and rescue assays were used to determine the correlations among circ_0007823, miR-182-5p, and FOXO1 expression. MiR-182-5p was overexpressed in DDP-resistant TNBC cells. MiR-182-5p knockdown suppressed the invasiveness and increased the apoptosis of drug-resistant cells, contributing to G1 arrest and S phase reduction. Mechanistically, circ_0007823 targeted miR-182-5p, and its overexpression drastically reduced the promotional effects of the miR-182-5p mimic on the aggression and transfer ability of drug-resistant cells. Furthermore, FOXO1 overexpression increased the sensitivity of cells to DDP and reduced their malignant progression. Therefore, FOXO1 was established as the downstream target of miR-182-5p that may be used to treat DDP-resistant TNBC. In summary, circ_0007823 overexpression attenuated DDP resistance in TNBC via the miR-182-5p-FOXO1 axis, indicating the therapeutic potential of circ_0007823 DDP-resistant TNBC treatment.

Impact of microplastic residues from polyurethane films on crop growth: Unraveling insights through transcriptomics and metabolomics analysis.

The utilisation of coated controlled-release fertilizers (CRFs) leads to the persistence of residual plastic films in agricultural soils, posing a potential threat to crop health. This study investigates the impacts of four residual films (0.39 %, w/w) derived from CRFs in soil, including petrochemical polyether, bio-based polyether, castor oil polyester, and wheat straw polyester polyurethane on wheat growth. This study found that PecPEUR significantly reduced wheat plant height, stem diameter, leaf area, and aboveground fresh weight by 24.8 %, 20.2 %, and 25.7 %. Through an in-depth exploration of transcriptomics and metabolomics, it has been discovered that all residual films disrupted glycolysis-related metabolic pathways in wheat roots, affecting seedling growth. Among them, PecPEUR significantly reduced the fresh weight of aboveground parts by 20.5 %. In contrast, polyester polyurethane residue had no discernible impact on aboveground wheat growth. This was attributed to the enrichment of wheat root genes in jasmonic acid and γ-aminobutyric acid metabolic pathways, thus mitigating oxidative stress, enhancing stress resistance, and ensuring normal plant growth. This study, for the first time, provides comprehensive insights into the effects of polyurethane film residue on wheat seedling growth, underscoring its potential as a promising alternative to conventional plastics in soil.

Dosimetric characterization for GRID collimator-based spatially fractionated radiation therapy: Dosimetric parameter acquisition and machine interchangeability investigation.

PURPOSE: The purpose of this study is to characterize the dosimetric properties of a commercial brass GRID collimator for high energy photon beams including 15 and 10 MV. Then, the difference in dosimetric parameters of GRID beams among different energies and linacs was evaluated. METHOD: A water tank scanning system was used to acquire the dosimetric parameters, including the percentage depth dose (PDD), beam profiles, peak to valley dose ratios (PVDRs), and output factors (OFs). The profiles at various depths were measured at 100 cm source to surface distance (SSD), and field sizes of 10 × 10 cm2 and 20 × 20 cm2 on three linacs. The PVDRs and OFs were measured and compared with the treatment planning system (TPS) calculations. RESULTS: Compared with the open beam data, there were noticeable changes in PDDs of GRID fields across all the energies. The GRID fields demonstrated a maximal of 3 mm shift in dmax (Truebeam STX, 15MV, 10 × 10 cm2). The PVDR decreased as beam energy increases. The difference in PVDRs between Trilogy and Truebeam STx using 6MV and 15MV was 1.5% ± 4.0% and 2.1% ± 4.3%, respectively. However, two Truebeam linacs demonstrated less than 2% difference in PVDRs. The OF of the GRID field was dependent on the energy and field size. The measured PDDs, PVDRs, and OFs agreed with the TPS calculations within 3% difference. The TPS calculations agreed with the measurements when using 1 mm calculation resolution. CONCLUSION: The dosimetric characteristics of high-energy GRID fields, especially PVDR, significantly differ from those of low-energy GRID fields. Two Truebeam machines are interchangeable for GRID therapy, while a pronounced difference was observed between Truebeam and Trilogy. A series of empirical equations and reference look-up tables for GRID therapy can be generated to facilitate clinical applications.

Nomogram for predicting the risk of nonalcoholic fatty liver disease in older adults in Qingdao, China: A cross-sectional study.

BACKGROUND AND OBJECTIVES: To explore the risk factors for non-alcoholic fatty liver disease (NAFLD) and to establish a non-invasive tool for the screening of NAFLD in an older adult population. METHODS AND STUDY DESIGN: A total of 131,161 participants were included in this cross-sectional study. Participants were randomly divided into training and validation sets (7:3). The least absolute shrinkage and selection operator method was used to screen risk factors. Multivariate logistic regression was employed to develop a nomogram, which was made available online. Receiver operating characteristic curve analysis, calibration plots, and decision curve analysis were used to validate the discrimination, calibration, and clinical practicability of the nomogram. Sex and age subgroup analyses were conducted to further validate the reliability of the model. RESULTS: Nine variables were identified for inclusion in the nomogram (age, sex, waist circumference, body mass index, exercise frequency, systolic blood pressure, fasting plasma glucose, alanine aminotransferase, and low-density lipoprotein cholesterol). The area under the receiver operating characteristic curve values were 0.793 and 0.790 for the training set and the validation set, respectively. The calibration plots and decision curve analyses showed good calibration and clinical utility. Subgroup analyses demonstrated consistent discriminatory ability in different sex and age subgroups. CONCLUSIONS: This study established and validated a new nomogram model for evaluating the risk of NAFLD among older adults. The nomogram had good discriminatory performance and is a non-invasive and convenient tool for the screening of NAFLD in older adults.