Deficiency of DDX3X results in neurogenesis defects and abnormal behaviors via dysfunction of the Notch signaling.

The molecular mechanisms underlying the neurodevelopmental disorders (NDDs) caused by DDX3X variants remain poorly understood. In this study, we validated that de novo DDX3X variants are enriched in female developmental delay (DD) patients and mainly affect the evolutionarily conserved amino acids based on a meta-analysis of 46,612 NDD trios. We generated a ddx3x deficient zebrafish allele, which exhibited reduced survival rate, DD, microcephaly, adaptation defects, anxiolytic behaviors, social interaction deficits, and impaired spatial recognitive memory. As revealed by single-nucleus RNA sequencing and biological validations, ddx3x deficiency leads to reduced neural stem cell pool, decreased total neuron number, and imbalanced differentiation of excitatory and inhibitory neurons, which are responsible for the behavioral defects. Indeed, the supplementation of L-glutamate or glutamate receptor agonist ly404039 could partly rescue the adaptation and social deficits. Mechanistically, we reveal that the ddx3x deficiency attenuates the stability of the crebbp mRNA, which in turn causes downregulation of Notch signaling and defects in neurogenesis. Our study sheds light on the molecular pathology underlying the abnormal neurodevelopment and behavior of NDD patients with DDX3X mutations, as well as providing potential therapeutic targets for the precision treatment.

[A clinical study on the optimal placement depth for peripherally inserted central catheter through the great saphenous vein in preterm infants]. / 早产儿经大隐静脉行PICCç½®ç®¡æœ€ä½³ç½®ç®¡æ·±åº¦çš„ä¸´åºŠç ”ç©¶.

OBJECTIVES: To investigate the correlation between optimal placement depth (OPD) and physical measurement parameters in preterm infants receiving placement of peripherally inserted central catheter (PICC) through the great saphenous vein (GSV), and to establish a predictive formula for OPD during the placement of PICC through the GSV. METHODS: A retrospective analysis was performed for the preterm infants who received the placement of PICC through the GSV in the Neonatal Intensive Care Unit of the Third Xiangya Hospital of Central South University from December 2022 to February 2024. According to the site of puncture [GSV of the knee joint (KJ) or the ankle joint (AJ)], they were divided into a GSV-KJ placement group (n=38) and a GSV-AJ placement group (n=33). The infants were measured in terms of body weight (BW), body length, the length of the upper and lower parts of the body, head circumference, and abdominal circumference at the time of placement. The Pearson correlation analysis was used to investigate the correlation between the above variables and OPD. A predictive formula was established for OPD in the placement of PICC via the GSV in preterm infants, and the predicted residual between the predicted depth and the ideal OPD was compared between the conventional predictive formula and the new predictive formula. RESULTS: The Pearson correlation analysis showed that PICC OPD was significantly positively correlated with BW, body length, the length of the upper and lower parts of the body, head circumference, and abdominal circumference in both the GSV-KJ placement group and GSV-AJ placement group (P<0.05), with the highest degree of correlation between OPD and BW. The univariate linear regression analysis showed a linear relationship between PICC OPD and BW in both groups. The predictive formulas for OPD were as follows: GSV-KJ PICC OPD (cm) = 13.1 + 2.7 × BW (kg) and GSV-AJ PICC OPD (cm) = 13.4 + 6.0 × BW (kg), and the new predictive formulas had a significantly lower predicted residual than the conventional predictive formula (P<0.05). CONCLUSIONS: OPD for PICC through the GSV is positively correlated with BW, and the prediction results of the new predictive formula based on BW are closer to the ideal OPD.

Supplementation of spermidine enhances the quality of postovulatory aged porcine oocytes.

BACKGROUND: Spermidine (SPD) is an intermediate compound in the polyamine metabolism which takes critical part in a variety of cellular processes. In particular, it has been reported to exert anti-aging effects, suppress the age-related diseases, and extend lifespan across species. However, whether it has the favorable influence on the quality of postovulatory aged oocytes remains elusive. METHODS: Immunostaining and fluorescence intensity measurement were used to evaluate the effects of postovulatory aging and SPD supplementation on the oocyte fragmentation, spindle/chromosome structure, actin polymerization, dynamics of cortical granules (CGs) and ovastacin, mitochondrial distribution and function, as well as autophagy levels. In addition, in vitro sperm binding assay and in vitro fertilization (IVF) experiment were applied to assess the impacts of postovulatory aging and SPD supplementation on the sperm binding ability and fertilization capacity of oocytes. RESULTS: Here, we showed that supplementation of SPD during postovulatory aging could relieve the deterioration of porcine oocytes. Specifically, we found that postovulatory aging impaired the oocyte quality by damaging the morphological integrity of oocytes, maintenance of spindle/chromosome structure, and dynamics of actin cytoskeleton. Postovulatory aging also weakened the sperm binding ability and fertilization capacity of oocytes by compromising the distribution pattern of CGs and their content ovastacin. Notably, supplementation of SPD attenuated these defects in postovulatory aged porcine oocytes via strengthening mitochondrial function, eliminating excessive reactive oxygen species (ROS), inhibiting apoptosis, and enhancing autophagy levels. CONCLUSION: Altogether, our findings demonstrate that SPD supplementation is a feasible approach to ameliorate the quality of postovulatory aged oocytes, which can be potentially applied to the human assisted reproductive technology (ART) and in vitro production of animal embryos.

Genetic and Environmental Factors Co-Contributing to Behavioral Abnormalities in adnp/adnp2 Mutant Zebrafish.

Human mutations of ADNP and ADNP2 are known to be associated with neural developmental disorders (NDDs), including autism spectrum disorders (ASDs) and schizophrenia (SZ). However, the underlying mechanisms remain elusive. In this study, using CRISPR/Cas9 gene editing technology, we generated adnp and adnp2 mutant zebrafish models, which exhibited developmental delays, brain deficits, and core behavioral features of NDDs. RNA sequencing analysis of adnpa-/-; adnpb-/- and adnp2a-/-; adnp2b-/- larval brains revealed altered gene expression profiles affecting synaptic transmission, autophagy, apoptosis, microtubule dynamics, hormone signaling, and circadian rhythm regulation. Validation using whole-mount in situ hybridization (WISH) and real-time quantitative PCR (qRT-PCR) corroborated these findings, supporting the RNA-seq results. Additionally, loss of adnp and adnp2 resulted in significant downregulation of pan-neuronal HuC and neuronal fiber network α-Tubulin signals. Importantly, prolonged low-dose exposure to environmental endocrine disruptors (EEDs) aggravated behavioral abnormalities in adnp and adnp2 mutants. This comprehensive approach enhances our understanding of the complex interplay between genetic mutations and environmental factors in NDDs. Our findings provide novel insights and experimental foundations into the roles of adnp and adnp2 in neurodevelopment and behavioral regulation, offering a framework for future preclinical drug screening aimed at elucidating the pathogenesis of NDDs and related conditions.

Low-intensity focused ultrasound combined with microbubbles for non-invasive downregulation of rabbit carotid body activity in the treatment of hypertension.

Targeting the carotid body (CB) is a new approach in treating hypertension. This study investigates the efficacy and safety of ultrasound combined with microbubbles in targeting CB to treat hypertension. Twenty-seven hypertensive rabbits were randomly assigned to three groups: microbubbles only (sham group, n = 11), ultrasound plus microbubbles (LIFU group, n = 11), and bilateral carotid sinus nerve denervation (CSND group, n = 5). Four weeks post-intervention, blood pressure, hypoxic ventilatory response (HVR), blood pressure variability (BPV), heart rate variability (HRV), biochemical indicators, neurohormones, and histopathology were assessed in all groups. The results indicated significant reductions in systolic and diastolic blood pressure in the LIFU and CSND groups post-intervention, along with decreases in BPV, HRV, and catecholamines. HVR results showed a 35.10% reduction in CB activity in the LIFU group compared to the sham group, which was significantly lower than the reduction in the CSND group compared to the sham group (73.85%). Histopathology and transmission electron microscopy confirmed CB damage and cell apoptosis, with immunofluorescence showing a reduction in type I and II cells. In conclusion, LIFU combined with microbubbles can reduce blood pressure by lowering CB and sympathetic nerve activity.

ARHGAP26 deficiency drives the oocyte aneuploidy and early embryonic development failure.

Aneuploidy, the presence of a chromosomal anomaly, is a major cause of spontaneous abortions and recurrent pregnancy loss in humans. However, the underlying molecular mechanisms still remain poorly understood. Here, we report that ARHGAP26, a putative tumor suppressor gene, is a newly identified regulator of oocyte quality to maintain mitochondrial integrity and chromosome euploidy, thus ensuring normal embryonic development and fertility. Taking advantage of knockout mouse model, we revealed that genetic ablation of Arhgap26 caused the oocyte death at GV stage due to the mitochondrial dysfunction-induced ROS accumulation. Lack of Arhgap26 also impaired both in vitro and in vivo maturation of survived oocytes which results in maturation arrest and aneuploidy, and consequently leading to early embryonic development defects and subfertility. These observations were further verified by transcriptome analysis. Mechanistically, we discovered that Arhgap26 interacted with Cofilin1 to maintain the mitochondrial integrity by regulating Drp1 dynamics, and restoration of Arhgap26 protein level recovered the quality of Arhgap26-null oocytes. Importantly, we found an ARHGAP26 mutation in a patient with history of recurrent miscarriage by chromosomal microarray analysis. Altogether, our findings uncover a novel function of ARHGAP26 in the oocyte quality control and prevention of aneuploidy and provide a potential treatment strategy for infertile women caused by ARHGAP26 mutation.

Mitigating citrus fruit cracking: the efficacy of chelated calcium or silicon foliar fertilizers in 'Okitsu no. 58' citrus fruit.

The 'Okitsu No. 58' citrus variety is highly prone to fruit cracking, which jeopardizes yield and results in economic losses. In this study, we investigated the impacts of spraying 5 distinct concentrations (0.1, 0.2, 0.3, 0.4, and 0.5 g/L) of chelated calcium (Ca) or silicon (Si) fertilizers at the young fruit stage (60-90 days after flowering, DAF) on fruit cracking and quality in the citrus variety 'Okitsu No. 58'. The results showed either Ca or Si fertilizer treatments reduced fruit cracking. We found that all Ca and partial Si treatments (0.4 and 0.5 g/L) significantly promoted the accumulation of Ca content in the peel. Notably, Ca or Si treatments significantly reduced polygalacturonase (PG) activity and inhibited the production of water-soluble pectin (WSP) in the peel. Additionally, Ca or Si treatments elevated the superoxide dismutase (SOD) activity and decreased the malondialdehyde (MDA) content of the peels. Changes in these parameters likely contributed to strengthening the durability of peel cell wall constituents, thus enhancing the fruit's resistance to fruit cracking. Overall, except for the C3 (0.3 g/L of Ca), Ca or Si fertilizers contributed to fruit conventional quality, mainly in terms of higher soluble sugars (SS) and SS/TA (titratable acid). Therefore, our findings will provide a reference for the prevention and control of citrus fruit cracking and the development of new fertilizers.

Multifaceted anomaly detection framework for leachate monitoring in landfills.

The imperative to preserve environmental resources has transcended traditional conservation efforts, becoming a crucial element for sustaining life. Our deep interconnectedness with the natural environment, which directly impacts our well-being, emphasizes this urgency. Contaminants such as leachate from landfills are increasingly threatening groundwater, a vital resource that provides drinking water for nearly half of the global population. This critical environmental threat requires advanced detection and monitoring solutions to effectively safeguard our groundwater resources. To address this pressing need, we introduce the Multifaceted Anomaly Detection Framework (MADF), which integrates Electrical Resistivity Tomography (ERT) with advanced machine learning models-Isolation Forest (IF), One-Class Support Vector Machines (OC-SVM), and Local Outlier Factor (LOF). MADF processes and analyzes ERT data, employing these hybrid machine learning models to identify and quantify anomaly signals accurately via the majority vote strategy. Applied to the Chaling landfill site in Zhuzhou, China, MADF demonstrated significant improvements in detection capability. The framework enhanced the precision of anomaly detection, evidenced by higher Youden Index values (≈ 6.216%), with a 30% increase in sensitivity and a 25% reduction in false positives compared to traditional ERT inversion methods. Indeed, these enhancements are crucial for effective environmental monitoring, where the cost of missing a leak could be catastrophic, and for reducing unnecessary interventions that can be resource-intensive. These results underscore MADF's potential as a robust tool for proactive environmental management, offering a scalable and adaptable solution for comprehensive landfill monitoring and pollution prevention across varied environmental settings.

Volatile metabolomics and transcriptomics analyses provide insights into the mechanism of volatile changes during fruit development of 'Ehime 38' (Citrus reticulata) and its bud mutant.

Volatile compounds are important determinants affecting fruit flavor. Previous study has identified a bud mutant of 'Ehime 38' (Citrus reticulata) with different volatile profile. However, the volatile changes between WT and MT during fruit development and underlying mechanism remain elusive. In this study, a total of 35 volatile compounds were identified in the pulps of WT and MT at five developmental stages. Both varieties accumulated similar and the highest levels of volatiles at stage S1, and showed a downward trend as the fruit develops. However, the total volatile contents in the pulps of MT were 1.4-2.5 folds higher than those in WT at stages S2-S5, which was mainly due to the increase in the content of d-limonene. Transcriptomic and RT-qPCR analysis revealed that most genes in MEP pathway were positively correlated with the volatile contents, of which DXS1 might mainly contribute to the elevated volatiles accumulation in MT by increasing the flux into the MEP pathway. Moreover, temporal expression analysis indicated that these MEP pathway genes functioned at different developmental stages. This study provided comprehensive volatile metabolomics and transcriptomics characterizations of a citrus mutant during fruit development, which is valuable for fruit flavor improvement in citrus.

Realizing highly efficient vertical coupling with dielectric deflective metasurfaces.

Using dielectric deflective metasurfaces, we propose a novel, to the best of our knowledge, out-of-plane modulation scheme to realize vertical coupling on a 220 nm silicon-on-insulator platform. The metasurface is used to deflect vertical incident light to an oblique angle with high efficiency in the cladding layer. This deflection introduces a lateral wave vector component, thus preventing bi-directional transmission of traditional vertical coupling due to the second-order Bragg reflection of the grating. Additionally, an apodized design is employed for the subwavelength grating to improve mode matching with a deflection angle incident. The integration of the metasurface and subwavelength grating enables a new vertical coupling scheme with high efficiency. After global optimization, we achieved a simulation coupling efficiency of -2.19 dB. The measured coupling efficiency is -3.36 dB with a center wavelength of 1545.6 nm and a 1-dB bandwidth of 32 nm. The results confirm the feasibility of the proposed new architecture.

Bioinformatics analysis of PANoptosis regulators in the diagnosis and subtyping of steroid-induced osteonecrosis of the femoral head.

In this study, we aimed to investigate the involvement of PANoptosis, a form of regulated cell death, in the development of steroid-induced osteonecrosis of the femoral head (SONFH). The underlying pathogenesis of PANoptosis in SONFH remains unclear. To address this, we employed bioinformatics approaches to analyze the key genes associated with PANoptosis. Our analysis was based on the GSE123568 dataset, allowing us to investigate both the expression profiles of PANoptosis-related genes (PRGs) and the immune profiles in SONFHallowing us to investigate the expression profiles of PRGs as well as the immune profiles in SONFH. We conducted cluster classification based on PRGs and assessed immune cell infiltration. Additionally, we used the weighted gene co-expression network analysis (WGCNA) algorithm to identify cluster-specific hub genes. Furthermore, we developed an optimal machine learning model to identify the key predictive genes responsible for SONFH progression. We also constructed a nomogram model with high predictive accuracy for assessing risk factors in SONFH patients, and validated the model using external data (area under the curve; AUC = 1.000). Furthermore, we identified potential drug targets for SONFH through the Coremine medical database. Using the optimal machine learning model, we found that 2 PRGs, CASP1 and MLKL, were significantly correlated with the key predictive genes and exhibited higher expression levels in SONFH. Our analysis revealed the existence of 2 distinct PANoptosis molecular subtypes (C1 and C2) within SONFH. Importantly, we observed significant variations in the distribution of immune cells across these subtypes, with C2 displaying higher levels of immune cell infiltration. Gene set variation analysis indicated that C2 was closely associated with multiple immune responses. In conclusion, our study sheds light on the intricate relationship between PANoptosis and SONFH. We successfully developed a risk predictive model for SONFH patients and different SONFH subtypes. These findings enhance our understanding of the pathogenesis of SONFH and offer potential insights into therapeutic strategies.

Establishment of a model of LPS-induced inflammatory injury in human aortic endothelial cells.

PURPOSE: We aim to establish an LPS-induced human aortic endothelial cells (HAECs) inflammatory injury model and explore the optimal conditions for inducing its injury. We expect to provide modeling references for the related experiments of vascular inflammatory diseases. METHODS: HAECs were cultured in vitro and treated with different concentrations of lipopolysaccharide (LPS) (0.1, 1, 10, 50, 100 µg/mL) for 6, 12, and 24 h to establish the HAECs inflammatory injury model. The cell viability was determined by CCK-8 assay; the expression levels of inflammatory cytokines in the cells were detected by RT-PCR；the apoptosis rate of the cells was detected by flow cytometry. RESULTS: ① Within 24 h of LPS treatment, the cell viability of the 0.1 and 1 µg/mL groups showed an overall increasing trend with time, while the cell viability of the 10, 50, and 100 µg/mL groups increased first and then decreased with time, and the cell viability of 50 and 100 µg/mL groups was significantly lower than the normal control group at 24 h (P<0.01). ② RT-PCR results showed that after 50 and 100 µg/mL LPS for 24 h, the inflammatory cytokines all showed an apparent upward trend compared with the normal control group (P<0.05), which was more significant in the 100 µg/mL group. ③ After 100 µg/mL LPS for 24 h, the apoptotic necrosis rate of HAECs was higher than the normal control group (P<0.01). CONCLUSIONS: This experiment successfully established a HAECs injury model, indicating that the optimal conditions for inducing injury are an LPS concentration of 100 µg/mL and a treatment time of 24 h.

Genome-Wide Analysis of the GLK Gene Family and Its Expression at Different Leaf Ages in the Citrus Cultivar Kanpei.

The GLK gene family plays a crucial role in the regulation of chloroplast development and participates in chlorophyll synthesis. However, the precise mechanism by which GLK contributes to citrus's chlorophyll synthesis remains elusive. The GLK gene family causes variations in the photosynthetic capacity and chlorophyll synthesis of different citrus varieties. In this study, we identified tissue-specific members and the key CcGLKs involved in chlorophyll synthesis. A total of thirty CcGLK transcription factors (TFs) were discovered in the citrus genome, distributed across all nine chromosomes. The low occurrence of gene tandem duplication events and intronic variability suggests that intronic variation may be the primary mode of evolution for CcGLK TFs. Tissue-specific expression patterns were observed for various GLK family members; for instance, CcGLK12 and CcGLK15 were specifically expressed in the skin, while CcGLK30 was specific to the ovary, and CcGLK10, CcGLK6, CcGLK21, CcGLK2, CcGLK18, CcGLK9, CcGLK28, and CcGLK8 were specifically expressed in the leaves. CcGLK4, CcGLK5, CcGLK11, CcGLK23, CcGLKl7, CcGLK26, and CcGLK20 may participate in the regulation of the ALA, prochlorophylate, protoporphyrin IX, Mg-protoporphyrin IX, Chl b, T-Chl, MG-ProtoIX ME, and POR contents in citrus.

Triglyceride-glucose index predicts sepsis-associated acute kidney injury and length of stay in sepsis: A MIMIC-IV cohort study.

Background: Inflammation and stress response may be related to the occurrence of sepsis-associated acute kidney injury (SA-AKI) in patients with sepsis.Insulin resistance (IR) is closely related to the stress response, inflammatory response, immune response and severity of critical diseases. We assume that the triglyceride-glucose (TyG) index, an alternative indicator for IR, is associated with the occurrence of SA-AKI in patients with sepsis. Methods: Data were obtained from The Medical Information Mart for Intensive Care-IV(MIMIC-IV) database in this retrospective cohort study. Univariate and multivariate logistic regression analysis and multivariate restricted cubic spline(RCS) regression were conducted to evaluate the association between TyG index and SA-AKI, length of stay (LOS). Subgroup and sensitivity analyses were performed to verify the robustness of the results. Results: The study ultimately included data from 1426 patients with sepsis, predominantly of white ethnicity (59.2%) and male sex (56.4%), with an SA-AKI incidence rate of 78.5%. A significant linear association was observed between the TyG index and SA-AKI (OR, 1.40; 95% confidence interval(CI) [1.14-1.73]). Additionally, the TyG index demonstrated a significant correlation with the length of stay (LOS) in both the hospital (ß, 1.79; 95% CI [0.80-2.77]) and the intensive care unit (ICU) (ß, 1.30; 95% CI [0.80-1.79]). Subgroup and sensitivity analyses confirmed the robustness of these associations. Conclusion: This study revealed a strong association between the TyG index and both SA-AKI and length of stay in patients with sepsis. These findings suggest that the TyG index is a potential predictor of SA-AKI and the length of hospitalization in sepsis cases, broadening its application in this context. However, further research is required to confirm whether interventions targeting the TyG index can genuinely enhance the clinical outcomes of patients with sepsis.

Analysis of sugar components and identification of SPS genes in citrus fruit development.

Sugar is a primary determinant of citrus fruit flavour, but undergoes varied accumulation processes across different citrus varieties owing to high genetic variability. Sucrose phosphate synthase (SPS), a key enzyme in glucose metabolism, plays a crucial role in this context. Despite its significance, there is limited research on sugar component quality and the expression and regulatory prediction of SPS genes during citrus fruit development. Therefore, we analysed the sugar quality formation process in 'Kiyomi' and 'Succosa', two citrus varieties, and performed a comprehensive genome-wide analysis of citrus CsSPSs. We observed that the accumulation of sugar components significantly differs between the two varieties, with the identification of four CsSPSs in citrus. CsSPS sequences were highly conserved, featuring typical SPS protein domains. Expression analysis revealed a positive correlation between CsSPS expression and sugar accumulation in citrus fruits. However, CsSPS expression displays specificity to different citrus tissues and varieties. Transcriptome co-expression network analysis suggests the involvement of multiple transcription factors in shaping citrus fruit sugar quality through the regulation of CsSPSs. Notably, the expression levels of four CsWRKYs (CsWRKY2, CsWRKY20, CsWRKY28, CsWRKY32), were significantly positively correlated with CsSPSs and CsWRKY20 might can activate sugar accumulation in citrus fruit through CsSPS2. Collectively, we further emphasize the potential importance of CsWRKYs in citrus sugar metabolism, our findings serve as a reference for understanding sugar component formation and predicting CsSPS expression and regulation during citrus fruit development.

Identification of signaling pathways that specify a subset of migrating enteric neural crest cells at the wavefront in mouse embryos.

During enteric nervous system (ENS) development, pioneering wavefront enteric neural crest cells (ENCCs) initiate gut colonization. However, the molecular mechanisms guiding their specification and niche interaction are not fully understood. We used single-cell RNA sequencing and spatial transcriptomics to map the spatiotemporal dynamics and molecular landscape of wavefront ENCCs in mouse embryos. Our analysis shows a progressive decline in wavefront ENCC potency during migration and identifies transcription factors governing their specification and differentiation. We further delineate key signaling pathways (ephrin-Eph, Wnt-Frizzled, and Sema3a-Nrp1) utilized by wavefront ENCCs to interact with their surrounding cells. Disruptions in these pathways are observed in human Hirschsprung's disease gut tissue, linking them to ENS malformations. Additionally, we observed region-specific and cell-type-specific transcriptional changes in surrounding gut tissues upon wavefront ENCC arrival, suggesting their role in shaping the gut microenvironment. This work offers a roadmap of ENS development, with implications for understanding ENS disorders.

A Novel Position-Sensitive Linear Winding Silicon Drift Detector.

A novel position-sensitive linear winding silicon drift detector (LWSDD) was designed and simulated. On the frontside (anode side), the collecting anodes were set on both sides of the detector, and an S-shaped linear winding cathode strip was arranged in the middle, which can realize independent voltage division and reduce the complexity of external bias resistor chain compared with the traditional linear silicon drift detector. The detectors were arranged in a butterfly shape, which increased the effective area of the detectors and improved the collection efficiency. The linear winding silicon drift detector can obtain one-dimensional position information by measuring the drift time of electrons. The 2D position information of the incident particle is obtained from the anodes coordinates of the readout signal. One-dimensional analytically exact solutions of electric potential and field were obtained for the first time for the linear winding silicon drift detector. The simulation results show that the electric potential distribution inside the detector is uniform, and the "drift channel" inside the detector points to the collecting anodes on both sides, which proves the reasonable and feasible design of the linear winding silicon drift detector.

PSMB2 plays an oncogenic role in glioma and correlates to the immune microenvironment.

There has been an upward trend in the incidence of glioma, with high recurrence and high mortality. The beta subunits of the 20S proteasome are encoded by the proteasome beta (PSMB) genes and may affect the proteasome's function in glioma, assembly and inhibitor binding. This study attempted to reveal the function of the proliferation and invasion of glioma cells, which is affected by proteasome 20S subunit beta 2 (PSMB2). We subjected the data downloaded from the TCGA database to ROC, survival, and enrichment analyses. After establishing the stable PSMB2 knockdown glioma cell line. We detect the changes in the proliferation, invasion and migration of glioma cells by plate colony formation assay, transwell assay, wound healing assay and flow cytometry and PSMB2 expression was verified by quantitative PCR and Western blotting to identify the mRNA and protein levels. PSMB2 expression was higher in glioma tissues, and its expression positively correlated with poor prognosis and high tumor grade and after PSMB2 knockdown, the proliferation, invasion and migration of glioma cells were weakened.

Effect of exogenous melatonin on antioxidant properties and fruit softening of 'Fengtang' plum fruit (Prunus salicina Lindl.) during storage at room temperature.

'Fengtang' plums soften quickly and lose flavor after harvest. This study comprehensively evaluated the effect of exogenous melatonin on the fruit quality of 'Fengtang' plums. According to our findings, exogenous melatonin prevented plum fruit from losing water, delayed the decline in firmness, and preserved a high TSS/TA level. Additionally, exogenous melatonin also enhanced the activity of antioxidant enzymes and increased the non-enzymatic antioxidants, thereby further increasing the antioxidant capacity of plum fruit. Notably, exogenous melatonin delayed the degradation of covalent soluble pectin (CSP), cellulose, and hemicellulose, as well as the rise in water-soluble pectin (WSP) concentration and the activity of cell wall degrading enzymes. Further investigation using atomic force microscopy (AFM) revealed that the chain-like structure of ionic-soluble pectin (ISP) and the self-assembly network structures of CSP were depolymerized, and melatonin treatment retarded the depolymerization of pectin structures. Our results showed that exogenous melatonin preserved the postharvest quality of plum fruits by controlling fruit softness and antioxidant capacity during storage.

Mesenchymal Stem Cells Attenuates Hirschsprung diseases - Associated Enterocolitis by Reducing M1 Macrophages Infiltration via COX-2 Dependent Mechanism.

OBJECTIVE AND DESIGN: Hirschsprung disease-associated enterocolitis (HAEC) is a common life-threatening complication of Hirschsprung disease (HSCR). We aimed to investigate the effectiveness, long-term safety and the underlying mechanisms of Mesenchymal stem cells (MSCs) based therapy for HAEC. MATERIAL OR SUBJECTS: Specimens from HSCR and HAEC patients were used to assess the inflammatory condition. Ednrb knock-out mice was used as HAEC model. MSCs was intraperitoneally transplanted into HAEC mice. The therapy effects, long-term outcome, safety and toxicity and the mechanism of MSCs on the treatment of HAEC were explored in vivo and in vitro. RESULTS: Intestinal M1 macrophages infiltration and severe inflammation condition were observed in HAEC. After the injection of MSCs, HAEC mice showed significant amelioration of the inflammatory injury and inhibition of M1 macrophages infiltration. The expression levels of pro-inflammatory cytokines (TNF-α and IFN-γ) were decreased and anti-inflammatory cytokines (IL-10 and TGF-ß) were increased. In addition, we found that effective MSCs homing to the inflamed colon tissue occurred without long-term toxicity response. However, COX-2 inhibitor could diminish the therapeutic effects of MSCs. Using MSCs and macrophages co-culture system, we identified that MSCs could alleviate HAEC by inhibiting M1 macrophages activation through COX-2-dependent MAPK/ERK signaling pathway. CONCLUSIONS: MSCs ameliorate HAEC by reducing M1 macrophages polarization via COX-2 mediated MAPK/ERK signaling pathway, thus providing novel insights and potentially promising strategy for the treatment or prevention of HAEC.