Effect of dexmedetomidine on ncRNA and mRNA profiles of cerebral ischemia-reperfusion injury in transient middle cerebral artery occlusion rats model.

Ischemic stroke poses a significant global health burden, with rapid revascularization treatments being crucial but often insufficient to mitigate ischemia-reperfusion (I/R) injury. Dexmedetomidine (DEX) has shown promise in reducing cerebral I/R injury, but its potential molecular mechanism, particularly its interaction with non-coding RNAs (ncRNAs), remains unclear. This study investigates DEX's therapeutic effect and potential molecular mechanisms in reducing cerebral I/R injury. A transient middle cerebral artery obstruction (tMACO) model was established to simulate cerebral I/R injury in adult rats. DEX was administered pre-ischemia and post-reperfusion. RNA sequencing and bioinformatic analyses were performed on the ischemic cerebral cortex to identify differentially expressed non-coding RNAs (ncRNAs) and mRNAs. The sequencing results showed 6,494 differentially expressed (DE) mRNA and 2698 DE circRNA between the sham and tMCAO (I/R) groups. Additionally, 1809 DE lncRNA, 763 DE mRNA, and 2795 DE circRNA were identified between the I/R group and tMCAO + DEX (I/R + DEX) groups. Gene ontology (GO) analysis indicated significant enrichment in multicellular biogenesis, plasma membrane components, and protein binding. KEGG analysis further highlighted the potential mechanism of DEX action in reducing cerebral I/R injury, with hub genes involved in inflammatory pathways. This study demonstrates DEX's efficacy in reducing cerebral I/R injury and offers insights into its brain-protective effects, especially in ischemic stroke. Further research is warranted to fully understand DEX's neuroprotective mechanisms and its clinical applications.

Black holes regulate cool gas accretion in massive galaxies.

The nucleus of almost all massive galaxies contains a supermassive black hole (BH)1. The feedback from the accretion of these BHs is often considered to have crucial roles in establishing the quiescence of massive galaxies2-14, although some recent studies show that even galaxies hosting the most active BHs do not exhibit a reduction in their molecular gas reservoirs or star formation rates15-17. Therefore, the influence of BHs on galaxy star formation remains highly debated and lacks direct evidence. Here, based on a large sample of nearby galaxies with measurements of masses of both BHs and atomic hydrogen (HI), the main component of the interstellar medium18, we show that the HI gas mass to stellar masses ratio (µHI = MHI/M⋆) is more strongly correlated with BH masses (MBH) than with any other galaxy parameters, including stellar mass, stellar mass surface density and bulge masses. Moreover, once the µHI-MBH correlation is considered, µHI loses dependence on other galactic parameters, demonstrating that MBH serves as the primary driver of µHI. These findings provide important evidence for how the accumulated energy from BH accretion regulates the cool gas content in galaxies, by ejecting interstellar medium gas and/or suppressing gas cooling from the circumgalactic medium.

Computed tomography (CT)-based skeletal muscle vertebral-related index to assess low muscle mass in patients with non-small cell lung cancer.

Background: Patients with lung cancer accompanied by sarcopenia may have a poor prognosis. Normally, low muscle mass associated with sarcopenia is assessed using the skeletal muscle index (SMI). It remains unclear whether the standardized skeletal muscle area (SMA) using 2-dimensional (2D) vertebral metrics (called the skeletal muscle vertebral related index, SMVI) could substitute for SMI when it is missing. The aim of this study was to investigate the feasibility of SMVI as an alternative to SMI, and their associations with overall survival (OS) in patients with non-small cell lung cancer (NSCLC). Methods: In this single-center study, a retrospective analysis was conducted on 433 NSCLC patients who underwent computed tomography (CT) scans. At the third lumbar vertebra (L3) level, measurements were taken for SMA, vertebral body area, transverse vertebral diameter (TVD), longitudinal vertebral diameter (LVD), and vertebral height (VH). The 4 SMVIs were skeletal muscle vertebral ratio (SMVR) (SMA/vertebral body area), skeletal muscle transverse vertebral diameter index (SMTVDI) (SMA/TVD2), skeletal muscle longitudinal vertebral diameter index (SMLVDI) (SMA/LVD2), and skeletal muscle vertebral height index (SMVHI) (SMA/VH2). The patients were categorized into low and high muscle mass groups based on SMI, and the differences in SMVIs between the 2 groups were compared to assess their correlation with SMI. Receiver operating characteristic (ROC) curves and the area under the curve (AUC) were utilized to assess the discriminatory ability. Kaplan-Meier curves were employed to compare the survival disparity between the 2 groups. Results: We included 191 male and 242 female patients in this study. Compared to the high muscle mass group, patients in the low muscle mass group exhibited significantly lower SMVR, SMTVDI, SMLVDI, and SMVHI (all P<0.05). All 4 SMVIs showed a positive correlation with SMI, with Spearman correlation coefficients of 0.83, 0.76, 0.75, and 0.67, respectively (all P<0.001). The AUC for diagnosing low muscle mass was higher than 0.8 for all 4 SMVI parameters. The Kaplan-Meier curve revealed that the low-risk group had a better survival probability than the high-risk group in the SMVR, SMTVDI, and SMLVDI. Conclusions: The SMVI functions as an alternative metric for evaluating skeletal muscle mass in the assessment of NSCLC based on SMI.

Negative association between Body Roundness Index and bone mineral density: insights from NHANES.

Background: Osteoporosis (OP), affecting millions around the globe, is a prevalent degenerative condition of the bones characterized by a decrease in bone mineral density (BMD) and an increase in bone fragility. A novel anthropometric measure, the Body Roundness Index (BRI), provides a more accurate assessment of body fat distribution compared to traditional metrics. Using data from the National Health and Nutrition Examination Survey (NHANES), this study aims to explore the relationship between BRI and total BMD in U.S. adults aged 20 and above. Methods: Data from NHANES (2011-2018) were examined, encompassing 9,295 participants following exclusions. Dual-energy X-ray absorptiometry (DXA) was employed to measure BMD. BRI was calculated using waist circumference (WC) and height. The study accounted for variables such as demographic traits, physical exam results, lab test findings, and survey responses. Weighted multivariable linear regression models and smooth curve fitting methods were utilized to assess the relationship between BRI and total BMD. Results: The research found a notable inverse relationship between BRI and total BMD. In the model with full adjustments, an increase of one unit in BRI was linked to a 0.0313 g/cm2 reduction in total BMD (P < 0.0001). Moreover, an inflection point was identified at BRI = 9.5229, where each one-unit rise in BRI beyond this threshold corresponded to a more substantial decrease in total BMD (0.0363 g/cm2). Analysis by subgroups revealed that this negative association was consistent across most demographic and health-related categories. Conclusions: The results demonstrate a notable inverse relationship between BRI and total BMD, indicating that a higher BRI could be associated with lower BMD and a potentially greater risk of developing OP. This underscores the significance of accounting for body fat distribution in preventing OP and advocates for the use of BRI as a valuable marker for early intervention approaches.

Bipolar disorder and oxidative stress: A bibliometric perspective.

OBJECTIVE: Accumulating evidence indicates that oxidative stress and the disruption of antioxidant defenses play an important role in the neurobiology of bipolar disorder (BD). Studies have found that increased oxidative stress may be associated with cell apoptosis and neuronal damage in BD patients. Hence, this study explored the research field related to BD and oxidative stress from a bibliometrics perspective. METHODS: Literature search and relevant data retrieval based on the Web of Sciences Core Collection (WoSCC). R software (version 4.2.2), VOSviewer software (version 1.6.18), and CiteSpace (version 6.1.6) were used in this bibliometric analysis. RESULTS: A total of 2081 publications related to BD and oxidative stress were published between 1986 and 2024. Bipolar Disorders was the journal that had the most publications in this area (72; 3.46%; IF = 5.9), while the United States (1285; 61.7%) and the University of Toronto (377; 18.1%) were the most productive country and institution, respectively. Apart from "oxidative stress" and "bipolar disorder," the most frequently used keywords were "schizophrenia," "prefrontal cortex," and "nitric oxide." CONCLUSIONS: The growing number of publications related to BD and oxidative stress in recent years highlights the importance of this research field. Hot topics in research related to BD and oxidative stress included animal experiments and molecular mechanisms, psychiatric-related inflammation and biomarkers, neurodegenerative diseases, and metabolism. Furthermore, the biological mechanisms of BD, particularly biomarkers and inflammation, may be the emerging research priority area in the future.

The clinical significance and anti-tumor role of PRKG1 in bladder cancer.

Introduction: cGMP-dependent protein kinase 1 (PRKG1) has shown to be associated with some tumorigenesis, while the role of PRKG1 in bladder cancer is unclear. Methods: To investigate the biological and clinical significance of PRKG1 in bladder cancer, we detected the expression of PRKG1 and explored the function of PRKG1 in bladder cancer cells. The PRKG1 transcripts data was downloaded from The Cancer Genome Atlas (TCGA) database, and immunohistochemistry staining was conducted on formalin-fixed paraffin-embedded (FFPE) sample tissues. Relationship between clinical characteristics of patients and expression of PRKG1 was analyzed in FFPE samples, TCGA database, and GSE19423 dataset. PRKG1 was over-expressed, and cell proliferation, migration, invasion, apoptosis, and spheroidizing ability were then detected. Chemosensitivity to cisplatin was detected with cell viability, and half-maximal drug inhibitory concentration (IC50) was calculated. In addition, the relation between PRKG1 expression and the infiltration level of tumor immune cells in tumor microenvironment were analyzed. Results: The results showed expression of PRKG1 was lower in bladder cancer, compared with normal tissues both at protein and transcript levels. Lower PRKG1 expression was related to higher tumor grade, T stage, and muscle invasion, also predicted worse overall survival and recurrence free survival in patients treated with Bacillus Calmette-Guerin (BCG) intravesical immunotherapy. Analysis of tumor immune cells infiltration showed lower PRKG1 was associated with non-inflamed tumor microenvironment. Conclusion: The present study firstly identified the anti-tumor role and tumor immune regulatory role of PRKG1, also found loss of PRKG1 could be used as a prognosis factor. The present study provided a potential biomarker and therapy target to bladder cancer.

Phosphorus fertilization enhanced overwintering, root system and forage yield of late-seeded alfalfa in sodic soils.

Sowing date and soil fertility are very important factors in the overwintering and production performance of alfalfa (Medicago sativa L.), yet there's a knowledge gap in knowledge on how late-seeded alfalfa responds to phosphorus (P) fertilization. A field study was conducted in Inner Mongolia from 2020 to 2022 using a split-plot design. The main plots consisted of five sowing dates (31 July, 8, 16, and 24 August, and 1 September), while the subplots involved five P application rates (0, 40, 70, 100, and 130 kg P2O5 ha-1). Throughout the growing seasons, the overwintering rate, root traits, forage yield, and yield components were measured. The results revealed a consistent decrease in overwintering ability and productivity with the delayed sowing. This reduction in overwintering rate was mainly due to diminished root traits, while the decrease in forage yield was largely associated with a reduction in plants per square meter. However, P fertilizer application to late-seeded alfalfa demonstrated potential in enhancing the diameter of both the crown and taproot, thus strengthening the root system and improving the overwintering rate, the rate of increase ranges from 11.6 to 49%. This adjustment could also improve the shoots per square meter and mass per shoot, increasing by 9.4-31.3% and 15.0-27.1% respectively in 2 years, which can offset the decline in forage yield caused by late sowing and might even increase the forage yield. Regression and path analysis indicated that alfalfa forage yield is primarily affected by mass per shoot rather than shoots per square meter. This study recommended that the sowing of alfalfa in similar regions of Inner Mongolia should not be later than mid-August. Moreover, applying P fertilizer (P2O5) at 70.6-85.9 kg ha-1 can enhance the forage yield and persistence of late-seeded alfalfa. Therefore, appropriate late sowing combined with the application of P fertilizer can be used as an efficient cultivation strategy for alfalfa cultivation after a short-season crop harvest in arid and cold regions.

Association of dietary live microbe intake with prevalence of osteoporosis in US postmenopausal women: a cross-sectional study.

The association between live microbe intake and osteoporosis in postmenopausal women remains unknown. The research findings indicated that an increased intake of live microbes through dietary sources was associated with a low prevalence of osteoporosis among postmenopausal women. PURPOSE: To investigate the relationship between the consumption of live microbes in the diet and osteoporosis in postmenopausal women. METHODS: A cross-sectional investigation using data obtained from the National Health and Nutrition Examination Survey was conducted. Participants were classified into three groups by using the dietary live microbe classification system developed by Sanders. Dual x-ray absorptiometry was used to measure body mineral density, and osteoporosis was diagnosed according to the World Health Organization criteria. We conducted a crude and adjusted multivariate logistic regression analysis, and utilized the restricted cubic splines model to assess the correlation between the consumption of live microbes in the diet and osteoporosis in postmenopausal women. RESULTS: A total of 1378 women who had undergone menopause were enrolled in the study. After controlling for potential covariates, individuals with a high consumption of live microbes in their diet exhibited a notably low prevalence of osteoporosis in comparison to those with a low intake of dietary live microbes (odd ratio: 0.46, 95% confidence interval: 0.23, 0.93, P = 0.03). Subgroup analysis showed the stability of the results, and restricted cubic splines showed an approximate L-shape curve. CONCLUSIONS: In this research, a higher consumption of live microbes in the diet was linked to a low prevalence of osteoporosis in postmenopausal women.

High-yield synthesis of hydroxylated boron nitride nanosheets and their utilization in thermally conductive polymeric nanocomposites.

Hexagonal boron nitride nanosheets (BNNSs) possess remarkable potential for various applications due to their unprecedented properties. However, the scalable production of BNNSs with both expansive surface and high solubility continues to present a significant challenge. Herein, we propose an innovative and efficient two-step method for manufacturing hydroxyl-functionalized BNNSs (OH-BNNSs). Initially, hydroxyl groups are covalently attached to bulk hexagonal boron nitride (h-BN) surfaces through H2O2 treatment. Then, the hydroxyl-functionalized h-BN undergoes exfoliation on account of a sudden increase in interlayer gas pressure generated by the vigorous decomposition of H2O2 in alkali solutions, resulting in the creation of OH-BNNSs. This approach produces relatively large flakes with an average dimension of 1.65 µm and a high yield of 45.2%. The resultant OH-BNNSs exhibit remarkable stability and dispersibility in a range of solvents. Their integration into thermoplastic polyurethane (TPU) significantly enhances both thermal conductivity and stability, attributed to the excellent compatibility with the resin matrix. This study represents a significant advancement in the functionalization and exfoliation of h-BN, opening new avenues for its promising applications in polymer composites.

Endocrine Outcomes and Associated Predictive Factors for Somatotrophin Pituitary Adenoma after Endoscopic Endonasal Transsphenoidal Surgery: 10 Years of Experience in a Single Institute.

Objective Biochemical remission rates of endoscopic endonasal transsphenoidal surgery (EETS) and its associated predictive factors were evaluated in patients with somatotrophin pituitary adenomas. Methods The patients who underwent EETS in Jinling Hospital were identified between 2011 and 2020. The surgeons' experience, preoperative insulin-like growth factor 1 (IGF-1), basal growth hormone (GH) levels, nadir GH levels, and the tumor characteristics were analyzed for their relationships with endocrine outcomes. Total 98 patients were included for single factor analysis and regression analysis. They were divided into three groups according to the admission chronologic order. Results The overall remission rate of the patients was 57% (56/98) for all the patients over 10 years. In the single factor analysis, we found that the tumor size, cavernous invasion, and sellar invasion were valuable to predict the endocrine outcome after surgery. As for the suprasellar invasion, no significant difference was found between the noninvasive group and the invasive group. The preoperative IGF-1 level ( p = 0.166), basal GH level ( p = 0.001), and nadir GH level ( p = 0.004) were also different between the remission group and the nonremission group in the single factor analysis. The logistic regression analysis indicated that the preoperative nadir GH (odds ratio = 0.930, 95% confidence interval = 0.891-0.972, p = 0.001) was a significant predictor for the endocrine outcomes after surgery. Conclusion The surgeons' experience is an important factor that can affect the patients' endocrine outcomes after surgery. The macroadenomas with lateral invasion are more difficult to cure. Patients with higher preoperative nadir GH levels are less likely to achieve remission.

Research on the osteogenic properties of 3D-printed porous titanium alloy scaffolds loaded with Gelma/PAAM-ZOL composite hydrogels.

Although titanium alloy is the most widely used endoplant material in orthopedics, the material is bioinert and good bone integration is difficult to achieve. Zoledronic acid (ZOL) has been shown to locally inhibit osteoclast formation and prevent osteoporosis, but excessive concentrations of ZOL exert an inhibitory effect on osteoblasts; therefore, stable and controlled local release of ZOL may reshape bone balance and promote bone regeneration. To promote the adhesion of osteoblasts to many polar groups, researchers have applied gelatine methacryloyl (Gelma) combined with polyacrylamide hydrogel (PAAM), which significantly increased the hydrogen bonding force between the samples and improved the stability of the coating and drug release. A series of experiments demonstrated that the Gelma/PAAM-ZOL bioactive coating on the surface of the titanium alloy was successfully prepared. The coating can induce osteoclast apoptosis, promote osteoblast proliferation and differentiation, achieve dual regulation of bone regeneration, successfully disrupt the balance of bone remodelling and promote bone tissue regeneration. Additionally, the coating improves the metal biological inertness on the surface of titanium alloys and improves the bone integration of the scaffold, offering a new strategy for bone tissue engineering to promote bone technology.

Sub-Nanosheet Induced Inverse Growth of Negative Valency Au Clusters for Tumor Treatment by Enhanced Oxidative Stress.

Cluster aggregation states are thermodynamically favored at the subnanoscale, for which an inverse growth from nanoparticles to clusters may be realized on subnanometer supports. Herein, we develop Au-polyoxometalate-layered double hydroxide (Au-POM-LDH) sub-1 nm nanosheets (Sub-APL) based on the above strategy, where sub-1 nm Au clusters with negative valence are generated by the in situ disintegration of Au nanoparticles on POM-LDH supports. Sub-1 nm Au clusters with ultrahigh surface atom ratios exhibit remarkable efficiency for glutathione (GSH) depletion. The closely connected sub-1 nm Au with negative valence and POM hetero-units can promote the separation of hole-electrons, resulting in the enhanced reactive oxygen species (ROS) generation under ultrasound (US). Besides, the reversible redox of Mo in POM is able to deplete GSH and trigger chemodynamic therapy (CDT) simultaneously, further enhancing the oxidative stress. Consequently, the Sub-APL present 2-fold ROS generation under US and 7-fold GSH depletion compared to the discrete Au and POM-LDH mixture. Therefore, the serious imbalance of redox in the TME caused by the sharp increase of ROS and rapid decrease of GSH leads to death of tumor ultimately.

Association of MRI findings with paraspinal muscles fat infiltration at lower lumbar levels in patients with chronic low back pain: a multicenter prospective study.

OBJECTIVE: In chronic low back pain (CLBP), the relationship between spinal pathologies and paraspinal muscles fat infiltration remains unclear. This study aims to evaluate the relationship between MRI findings and paraspinal muscles morphology and fat infiltration in CLBP patients by quantitative MRI. METHODS: All the CLBP patients were enrolled from July 2021 to December 2022 in four medical institutions. The cross-sectional area (CSA) and proton density fat fraction (PDFF) of the multifidus (MF) and erector spinae (ES) muscles at the central level of the L4/5 and L5/S1 intervertebral discs were measured. MRI findings included degenerative lumbar spondylolisthesis (DLS), intervertebral disc degeneration (IVDD), facet arthrosis, disc bulge or herniation, and disease duration. The relationship between MRI findings and the paraspinal muscles PDFF and CSA in CLBP patients was analyzed. RESULTS: A total of 493 CLBP patients were included in the study (198 females, 295 males), with an average age of 45.68 ± 12.91 years. Our research indicates that the number of MRI findings are correlated with the paraspinal muscles PDFF at the L4/5 level, but is not significant. Moreover, the grading of IVDD is the primary factor influencing the paraspinal muscles PDFF at the L4-S1 level (BES at L4/5=1.845, P < 0.05); DLS was a significant factor affecting the PDFF of MF at the L4/5 level (B = 4.774, P < 0.05). After including age, gender, and Body Mass Index (BMI) as control variables in the multivariable regression analysis, age has a significant positive impact on the paraspinal muscles PDFF at the L4-S1 level, with the largest AUC for ES PDFF at the L4/5 level (AUC = 0.646, cut-off value = 47.5), while males have lower PDFF compared to females. BMI has a positive impact on the ES PDFF only at the L4/5 level (AUC = 0.559, cut-off value = 24.535). CONCLUSION: The degree of paraspinal muscles fat infiltration in CLBP patients is related to the cumulative or synergistic effects of multiple factors, especially at the L4/L5 level. Although age and BMI are important factors affecting the degree of paraspinal muscles PDFF in CLBP patients, their diagnostic efficacy is moderate.

Catalpol reduced LPS induced BV2 immunoreactivity through NF-κB/NLRP3 pathways: an in Vitro and in silico study.

Background: Ischemic Stroke (IS) stands as one of the primary cerebrovascular diseases profoundly linked with inflammation. In the context of neuroinflammation, an excessive activation of microglia has been observed. Consequently, regulating microglial activation emerges as a vital target for neuroinflammation treatment. Catalpol (CAT), a natural compound known for its anti-inflammatory properties, holds promise in this regard. However, its potential to modulate neuroinflammatory responses in the brain, especially on microglial cells, requires comprehensive exploration. Methods: In our study, we investigated into the potential anti-inflammatory effects of catalpol using lipopolysaccharide (LPS)-stimulated BV2 microglial cells as an experimental model. The production of nitric oxide (NO) by LPS-activated BV2 cells was quantified using the Griess reaction. Immunofluorescence was employed to measure glial cell activation markers. RT-qPCR was utilized to assess mRNA levels of various inflammatory markers. Western blot analysis examined protein expression in LPS-activated BV2 cells. NF-κB nuclear localization was detected by immunofluorescent staining. Additionally, molecular docking and molecular dynamics simulations (MDs) were conducted to explore the binding affinity of catalpol with key targets. Results: Catalpol effectively suppressed the production of nitric oxide (NO) induced by LPS and reduced the expression of microglial cell activation markers, including Iba-1. Furthermore, we observed that catalpol downregulated the mRNA expression of proinflammatory cytokines such as IL-6, TNF-α, and IL-1ß, as well as key molecules involved in the NLRP3 inflammasome and NF-κB pathway, including NLRP3, NF-κB, caspase-1, and ASC. Our mechanistic investigations shed light on how catalpol operates against neuroinflammation. It was evident that catalpol significantly inhibited the phosphorylation of NF-κB and NLRP3 inflammasome activation, both of which serve as upstream regulators of the inflammatory cascade. Molecular docking and MDs showed strong binding interactions between catalpol and key targets such as NF-κB, NLRP3, and IL-1ß. Conclusion: Our findings support the idea that catalpol holds the potential to alleviate neuroinflammation, and it is achieved by inhibiting the activation of NLRP3 inflammasome and NF-κB, ultimately leading to the downregulation of pro-inflammatory cytokines. Catalpol emerges as a promising candidate for the treatment of neuroinflammatory conditions.

Risk Factors for 30-Day Mortality of Community-Acquired Bloodstream Infection Patients in Changsha City, Hunan Province, China.

Purpose: To analyze the factors affecting patients' prognoses based on the community acquired-bloodstream infection patient data from 2017 to 2021. Patients and Methods: The data of 940 patients were retrieved, having at least one positive bilateral blood culture within 48 hours of hospitalization, and grouped into survivor and non-survivor groups. The clinical characteristics, laboratory results, causative pathogen and other indicators were collected and compared, and risk factors were identified by applying Cox proportional hazard regression model to the data. Results: Community acquired-bloodstream infection is most commonly caused by Escherichia coli, Klebsiella species and Staphylococcus hominis. Among the total of 940 selected patients, 52 (5.5%) died during hospitalization. The demographic parameters like age and gender, clinical protocols like maintenance hemodialysis, glucocorticoid use during hospitalization, catheter placement, procaicitonin, total protein, albumin, creatinine, uric acid contents and Sequential Organ Failure Assessment scores were significantly different between the survivor and non-survivor groups. The survival analysis results revealed that age (HR=1.02, 95% CI: 1.00-1.05, P=0.002), glucocorticoid use during hospitalization (HR=3.69, 95% CI: 1.62-8.37, P=0.021) and Sequential Organ Failure Assessment score (HR=1.10, 95% CI: 1.03-1.18, P=0.004) might be the risk factors affecting 30-day mortality in patients with community acquired-bloodstream infection. Conclusion: The identified risk factors may help guide clinical treatment protocol for patients with community acquired-bloodstream infection, providing more effective treatment strategy selection with improved clinical outcomes.

GNAS mutations suppress cell invasion by activating MEG3 in growth hormone-secreting pituitary adenoma.

Approximately 30%-40% of growth hormone-secreting pituitary adenomas (GHPAs) harbor somatic activating mutations in GNAS (α subunit of stimulatory G protein). Mutations in GNAS are associated with clinical features of smaller and less invasive tumors. However, the role of GNAS mutations in the invasiveness of GHPAs is unclear. GNAS mutations were detected in GHPAs using a standard polymerase chain reaction (PCR) sequencing procedure. The expression of mutation-associated maternally expressed gene 3 (MEG3) was evaluated with RT-qPCR. MEG3 was manipulated in GH3 cells using a lentiviral expression system. Cell invasion ability was measured using a Transwell assay, and epithelial-mesenchymal transition (EMT)-associated proteins were quantified by immunofluorescence and western blotting. Finally, a tumor cell xenograft mouse model was used to verify the effect of MEG3 on tumor growth and invasiveness. The invasiveness of GHPAs was significantly decreased in mice with mutated GNAS compared with that in mice with wild-type GNAS. Consistently, the invasiveness of mutant GNAS-expressing GH3 cells decreased. MEG3 is uniquely expressed at high levels in GHPAs harboring mutated GNAS. Accordingly, MEG3 upregulation inhibited tumor cell invasion, and conversely, MEG3 downregulation increased tumor cell invasion. Mechanistically, GNAS mutations inhibit EMT in GHPAs. MEG3 in mutated GNAS cells prevented cell invasion through the inactivation of the Wnt/ß-catenin signaling pathway, which was further validated in vivo. Our data suggest that GNAS mutations may suppress cell invasion in GHPAs by regulating EMT through the activation of the MEG3/Wnt/ß-catenin signaling pathway.

The influence of activity patterns and relative humidity on particle resuspension in classrooms.

This paper investigates the impact of children's recess activity patterns on particulate matter (PM) resuspension in indoor environments, highlighting the complex, multi-dimensional nature of these activities and their interaction with environmental parameters. Despite the recognized role of indoor human activity in PM resuspension, research specifically addressing the effects of children's movements has been sparse. Through experimental scenarios that account for the characteristics of student activities, such as movement speed, trajectory, the number of participants, aisle widths, and varying humidity levels, this study uncovers significant differences in PM resuspension rates. It reveals that not only do movement speed and trajectory have a profound impact, but also the interaction between humidity and these factors plays a critical role, especially under lower humidity conditions. Additionally, the study demonstrates how the combination of people density and spatial configurations can significantly influence resuspension rates. The findings offer valuable insights for designing strategies to mitigate particle pollution in classrooms and similar indoor environments.

Characterization of a glycosyltransferase from Paris polyphylla for application in biosynthesis of rare ophiopogonins and ginsenosides.

Saponins are bioactive components of many medicinal plants, possessing complicated chemical structures and extensive pharmacological activities, but the production of high-value saponins remains challenging. In this study, a 6'-O-glucosyltransferase PpUGT7 (PpUGT91AH7) was functionally characterized from Paris polyphylla Smith var. yunnanensis (Franch.) Hand. -Mazz., which can transfer a glucosyl group to the C-6' position of diosgenin-3-O-rhamnosyl-(1 â†’ 2)-glucoside (1), pennogenin-3-O-rhamnosyl-(1 â†’ 2)-glucoside (2), and diosgenin-3-O-glucoside (5). The KM and Kcat values of PpUGT7 towards the substrate 2 were 8.4 µM and 2 × 10-3 s-1, respectively. Through molecular docking and site-directed mutagenesis, eight residues were identified to interact with the sugar acceptor 2 and be crucial for enzyme activity. Moreover, four rare ophiopogonins and ginsenosides were obtained by combinatorial biosynthesis, including an undescribed compound ruscogenin-3-O-glucosyl-(1 â†’ 6)-glucoside (10). Firstly, two monoglycosides 9 and 11 were generated using a known sterol 3-O-ß-glucosyltransferase PpUGT80A40 with ruscogenin (7) and 20(S)-protopanaxadiol (8) as substrates, which were further glycosylated to the corresponding diglycosides 10 and 12 under the catalysis of PpUGT7. In addition, compounds 7-11 were found to show inhibitory effects on the secretion of TNF-α and IL-6 in macrophages RAW264.7. The findings provide valuable insights into the enzymatic glycosylation processes in the biosynthesis of bioactive saponins in P. polyphylla var. yunnanensis, and also serve as a reference for utilizing UDP-glycosyltransferases to construct high-value or rare saponins for development of new therapeutic agents.

Insight into the bacterial community composition of the plastisphere in diverse environments of a coastal salt marsh.

The microbial community colonized on microplastics (MPs), known as the 'plastisphere', has attracted extensive concern owing to its environmental implications. Coastal salt marshes, which are crucial ecological assets, are considered sinks for MPs. Despite their strong spatial heterogeneity, there is limited information on plastisphere across diverse environments in coastal salt marshes. Herein, a 1-year field experiment was conducted at three sites in the Yancheng salt marsh in China. This included two sites in the intertidal zone, bare flat (BF) and Spartina alterniflora vegetation area (SA), and one site in the supratidal zone, Phragmites australis vegetation area (PA). Petroleum-based MPs (polyethylene and expanded polystyrene) and bio-based MPs (polylactic acid and polybutylene succinate) were employed. The results revealed significant differences in bacterial community composition between the plastisphere and sediment at all three sites examined, and the species enriched in the plastisphere exhibited location-specific characteristics. Overall, the largest difference was observed at the SA site, whereas the smallest difference was observed at the BF site. Furthermore, the MP polymer types influenced the composition of the bacterial communities in the plastisphere, also exhibiting location-specific characteristics, with the most pronounced impact observed at the PA site and the least at the BF site. The polybutylene succinate plastisphere bacterial communities at the SA and PA sites were quite different from the plastispheres from the other three MP polymer types. Co-occurrence network analyses suggested that the bacterial community network in the BF plastisphere exhibited the highest complexity, whereas the network in the SA plastisphere showed relatively sparse interactions. Null model analyses underscored the predominant role of deterministic processes in shaping the assembly of plastisphere bacterial communities across all three sites, with a more pronounced influence observed in the intertidal zone than in the supratidal zone. This study enriches our understanding of the plastisphere in coastal salt marshes.

A new evaluation system for drug-microbiota interactions.

The drug response phenotype is determined by a combination of genetic and environmental factors. The high clinical conversion failure rate of gene-targeted drugs might be attributed to the lack of emphasis on environmental factors and the inherent individual variability in drug response (IVDR). Current evidence suggests that environmental variables, rather than the disease itself, are the primary determinants of both gut microbiota composition and drug metabolism. Additionally, individual differences in gut microbiota create a unique metabolic environment that influences the in vivo processes underlying drug absorption, distribution, metabolism, and excretion (ADME). Here, we discuss how gut microbiota, shaped by both genetic and environmental factors, affects the host's ADME microenvironment within a new evaluation system for drug-microbiota interactions. Furthermore, we propose a new top-down research approach to investigate the intricate nature of drug-microbiota interactions in vivo. This approach utilizes germ-free animal models, providing foundation for the development of a new evaluation system for drug-microbiota interactions.