Neuregulin 1 mitigated prolactin deficiency through enhancing TRPM8 signaling under the influence of melatonin in senescent pituitary lactotrophs.

The age-related alterations in pituitary function, including changes in prolactin (PRL) production contributes to the systemic susceptibility to age-related diseases. Our previous research has shown the involvement of Nrg1 in regulating the expression and secretion of PRL. However, the precise role of Nrg1 in mitigating the senescence of pituitary lactotrophs and the underlying mechanisms are yet to be comprehended. Here, data from the GEPIA database was used to evaluate the association between transient receptor potential cation channel subfamily M member 8 (TRPM8) and PRL in normal human pituitary tissues, followed by immunofluorescence verification using a human pituitary tissue microarray. TRPM8 levels showed a significant positive association with PRL expression in normal human pituitary tissues, and both TRPM8 and PRL levels declined during aging, suggesting that TRPM8 may regulate pituitary aging by affecting PRL production. It was also found that treatment with exogenous neuregulin 1 (Nrg1) markedly delayed the senescence of GH3 cells (rat lactotroph cell line) generated by D-galactose (D-gal). In addition, melatonin reduced the levels of senescence-related markers in senescent pituitary cells by promoting Nrg1 / ErbB4 signaling, stimulating PRL expression and secretion. Further investigation showed that Nrg1 attenuated senescence in pituitary cells by increasing TRPM8 expression. Downregulation of TRPM8 activation eliminated Nrg1-mediated amelioration of pituitary cell senescence. These findings demonstrate the critical function of Nrg1 / ErbB signaling in delaying pituitary lactotroph cell senescence and enhancing PRL production via promoting TRPM8 expression under the modulation of melatonin.

Syntrophic methane production from volatile fatty acids: Focus on interspecies electron transfer.

Methane is a renewable biomass energy source produced via anaerobic digestion (AD). Interspecies electron transfer (IET) between methanogens and syntrophic bacteria is crucial for mitigating energy barriers in this process. Understanding IET is essential for enhancing the efficiency of syntrophic methanogenesis in anaerobic digestion. Interspecies electron transfer mechanisms include interspecies H2/formate transfer, direct interspecies electron transfer (DIET), and electron-shuttle-mediated transfer. This review summarizes the mechanisms, developments, and research gaps in IET pathways. Interspecies H2/formate transfer requires strict control of low H2 partial pressure and involves complex enzymatic reactions. In contrast, DIET enhances the electron transfer efficiency and process stability. Conductive materials and key microorganisms can be modulated to stimulate the DIET. Electron shuttles (ES) allow microorganisms to interact with extracellular electron acceptors without direct contact; however, their efficiency depends on various factors. Future studies should elucidate the key functional groups, metabolic pathways, and regulatory mechanisms of IET to guide the optimization of AD processes for efficient renewable energy production.

Diagnostic and prognostic role of LINC01767 in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a primary contributor to cancer-related mortality on a global scale. However, the underlying molecular mechanisms are still poorly understood. Long noncoding RNAs are emerging markers for HCC diagnosis, prognosis, and therapeutic target. No study of LINC01767 in HCC was published. AIM: To conduct a multi-omics analysis to explore the roles of LINC01767 in HCC for the first time. METHODS: DESeq2 Package was used to analyze different gene expressions. Receiver operating characteristic curves assessed the diagnostic performance. Kaplan-Meier univariate and Cox multivariate analyses were used to perform survival analysis. The least absolute shrinkage and selection operator (LASSO)-Cox was used to identify the prediction model. Subsequent to the validation of LINC01767 expression in HCC fresh frozen tissues through quantitative real time polymerase chain reaction, next generation sequencing was performed following LINC01767 over expression (GSE243371), and Gene Ontology/Kyoto Encyclopedia of Genes and Genomes/Gene Set Enrichment Analysis/ingenuity pathway analysis was carried out. In vitro experiment in Huh7 cell was carried out. RESULTS: LINC01767 was down-regulated in HCC with a log fold change = 1.575 and was positively correlated with the cancer stemness. LINC01767 was a good diagnostic marker with area under the curve (AUC) [0.801, 95% confidence interval (CI): 0.751-0.852, P = 0.0106] and an independent predictor for overall survival (OS) with hazard ratio = 1.899 (95%CI: 1.01-3.58, P = 0.048). LINC01767 nomogram model showed a satisfied performance. The top-ranked regulatory network analysis of LINC01767 showed the regulation of genes participating various pathways. LASSO regression identified the 9-genes model showing a more satisfied performance than 5-genes model to predict the OS with AUC > 0.75. LINC01767 was down-expressed obviously in tumor than para-tumor tissues in our cohort as well as in cancer cell line; the over expression of LINC01767 inhibit cell proliferation and clone formation of Huh7 in vitro. CONCLUSION: LINC01767 was an important tumor suppressor gene in HCC with good diagnostic and prognostic performance.

Recent advances in germinated cereal and pseudo-cereal starch: Properties and challenges in its modulation on quality of starchy foods.

Germination is an environmentally friendly process with no use of additives, during which only water spraying is done to activate endogenous enzymes for modification. Furthermore, it could induce bioactive phenolics accumulation. Controlling endogenous enzymes' activity is essential to alleviate granular disruption, crystallinity loss, double helices' dissociation, and molecular degradation of cereal and pseudo-cereal starch. Post-treatments (e.g. thermal and high-pressure technology) make it possible for damaged starch to reassemble towards well-packed structure. These contribute to alleviated loss of solubility and pasting viscosity, improved swelling power, or enhanced resistant starch formation. Cereal or pseudo-cereal flour (except that with robust structure) modified by early germination is more applicable to produce products with desirable texture and taste. Besides shortening duration, germination under abiotic stress is promising to mitigate starch damage for better utilization in staple foods.

Scutellarin Protects against Myocardial Ischemia-reperfusion Injury by Enhancing Aerobic Glycolysis through miR-34c-5p/ALDOA Axis.

Background: Aerobic glycolysis has recently demonstrated promising potential in mitigating the effects of ischemia-reperfusion (IR) injury. Scutellarin (Scu) possesses various cardioprotective properties that warrant investigation. To mimic IR injury in vitro, this study employed hypoxia/reoxygenation (H/R) injury. Methods and Results: First, we conducted an assessment of the protective properties of Scu against HR in H9c2 cells, encompassing inflammation damage, apoptosis injury, and oxidative stress. Then, we verified the effects of Scu on the Warburg effect in H9c2 cells during HR injury. The findings indicated that Scu augmented aerobic glycolysis by upregulating p-PKM2/PKM2 levels. Following, we built a panel of six long noncoding RNAs and seventeen microRNAs that were reported to mediate the Warburg effect. Based on the results, miR-34c-5p was selected for further experiments. Then, we observed Scu could mitigate the HR-induced elevation of miR-34c-5p. Upregulation of miR-34c-5p could weaken the beneficial impacts of Scu in cellular viability, inflammatory damage, oxidative stress, and the facilitation of the Warburg effect. Subsequently, our investigation revealed a decrease in both ALDOA mRNA and protein levels following HR injury, which could be restored by Scu administration. Downregulation of ALDOA or Mimic of miR-34c-5p could reduce these effects induced by Scu. Conclusions: Scu provides cardioprotective effects against IR injury by upregulating the Warburg effect via miR-34c-5p/ALDOA.

The relationship between atmospheric particulate matter, leaf surface microstructure, and the phyllosphere microbial diversity of Ulmus L.

BACKGROUND: Plants can retain atmospheric particulate matter (PM) through their unique foliar microstructures, which has a profound impact on the phyllosphere microbial communities. Yet, the underlying mechanisms linking atmospheric particulate matter (PM) retention by foliar microstructures to variations in the phyllosphere microbial communities remain a mystery. In this study, we conducted a field experiment with ten Ulmus lines. A series of analytical techniques, including scanning electron microscopy, atomic force microscopy, and high-throughput amplicon sequencing, were applied to examine the relationship between foliar surface microstructures, PM retention, and phyllosphere microbial diversity of Ulmus L. RESULTS: We characterized the leaf microstructures across the ten Ulmus lines. Chun exhibited a highly undulated abaxial surface and dense stomatal distribution. Langya and Xingshan possessed dense abaxial trichomes, while Lieye, Zuiweng, and Daguo had sparsely distributed, short abaxial trichomes. Duomai, Qingyun, and Lang were characterized by sparse stomata and flat abaxial surfaces, whereas Jinye had sparsely distributed but extensive stomata. The mean leaf retention values for total suspended particulate (TSP), PM2.5, PM2.5-10, PM10-100, and PM> 100 were 135.76, 6.60, 20.10, 90.98, and 13.08 µg·cm- 2, respectively. Trichomes substantially contributed to PM2.5 retention, while larger undulations enhanced PM2.5-10 retention, as evidenced by positive correlations between PM2.5 and abaxial trichome density and between PM2.5-10 and the adaxial raw microroughness values. Phyllosphere microbial diversity patterns varied among lines, with bacteria dominated by Sediminibacterium and fungi by Mycosphaerella, Alternaria, and Cladosporium. Redundancy analysis confirmed that dense leaf trichomes facilitated the capture of PM2.5-associated fungi, while bacteria were less impacted by PM and struggled to adhere to leaf microstructures. Long and dense trichomes provided ideal microhabitats for retaining PM-borne microbes, as evidenced by positive feedback loops between PM2.5, trichome characteristics, and the relative abundances of microorganisms like Trichoderma and Aspergillus. CONCLUSIONS: Based on our findings, a three-factor network profile was constructed, which provides a foundation for further exploration into how different plants retain PM through foliar microstructures, thereby impacting phyllosphere microbial communities.

Exploration of the combined role of immune checkpoints and immune cells in the diagnosis and treatment of ankylosing spondylitis: a preliminary study immune checkpoints in ankylosing spondylitis.

OBJECTIVE: Immune checkpoints have emerged as promising therapeutic targets for autoimmune diseases. However, the specific roles of immune checkpoints in the pathophysiology of ankylosing spondylitis (AS) remain unclear. METHODS: Hip ligament samples were obtained from two patient groups: those with AS and femoral head deformity, and those with femoral head necrosis but without AS, undergoing hip arthroplasty. Label-Free Quantification (LFQ) Protein Park Analysis was used to identify the protein composition of the ligaments. Peripheral blood samples of 104 AS patients from public database were used to validate the expression of key proteins. KEGG, GO, and GSVA were employed to explore potential pathways regulated by immune checkpoints in AS progression. xCell was used to calculate cell infiltration levels, LASSO regression was applied to select key cells, and the correlation between immune checkpoints and immune cells was analyzed. Drug sensitivity analysis was conducted to identify potential therapeutic drugs targeting immune checkpoints in AS. The expression of key genes was validated through immunohistochemistry (IHC). RESULTS: HLA-DMB and HLA-DPA1 were downregulated in the ligaments of AS and this has been validated through peripheral blood datasets and IHC. Significant differences in expression were observed in CD8 + Tcm, CD8 + T cells, CD8 + Tem, osteoblasts, Th1 cells, and CD8 + naive T cells in AS. The infiltration levels of CD8 + Tcm and CD8 + naive T cells were significantly positively correlated with the expression levels of HLA-DMB and HLA-DPA1. Immune cell selection using LASSO regression showed good predictive ability for AS, with AUC values of 0.98, 0.81, and 0.75 for the three prediction models, respectively. Furthermore, this study found that HLA-DMB and HLA-DPA1 are involved in Th17 cell differentiation, and both Th17 cell differentiation and the NF-kappa B signaling pathway are activated in the AS group. Drug sensitivity analysis showed that AS patients are more sensitive to drugs such as doramapimod and GSK269962A. CONCLUSION: Immune checkpoints and immune cells could serve as avenues for exploring diagnostic and therapeutic strategies for AS.

Identifying critical features of iron phosphate particle for lithium preference.

One-dimensional (1D) olivine iron phosphate (FePO4) is widely proposed for electrochemical lithium (Li) extraction from dilute water sources, however, significant variations in Li selectivity were observed for particles with different physical attributes. Understanding how particle features influence Li and sodium (Na) co-intercalation is crucial for system design and enhancing Li selectivity. Here, we investigate a series of FePO4 particles with various features and revealed the importance of harnessing kinetic and chemo-mechanical barrier difference between lithiation and sodiation to promote selectivity. The thermodynamic preference of FePO4 provides baseline of selectivity while the particle features are critical to induce different kinetic pathways and barriers, resulting in different Li to Na selectivity from 6.2 × 102 to 2.3 × 104. Importantly, we categorize the FePO4 particles into two groups based on their distinctly paired phase evolutions upon lithiation and sodiation, and generate quantitative correlation maps among Li preference, morphological features, and electrochemical properties. By selecting FePO4 particles with specific features, we demonstrate fast (636 mA/g) Li extraction from a high Li source (1: 100 Li to Na) with (96.6 ± 0.2)% purity, and high selectivity (2.3 × 104) from a low Li source (1: 1000 Li to Na) with (95.8 ± 0.3)% purity in a single step.

Deciphering immunodiffusion: In silico optimization for faster protein diagnostics.

Immunodiffusion tests offer a simple yet powerful method for detecting protein antigens, but their long assay times hinder clinical utility. We unveil the complex interplay of parameters governing this process using finite element simulations. By meticulously validating our model against real-world data, we elucidate how initial concentrations and diffusivities of antigen and antibody shape the intensity, size, and formation time of the precipitin ring. Our key innovation lies in employing phase diagram analysis to map the combined effects of these parameters on assay performance. This framework enables rapid in silico parameter estimation, paving the way for the design of novel immunodiffusion assays with drastically reduced assay times. The presented approach holds immense potential for optimizing protein diagnostics for fast and reliable diagnostics.

Urinary haloacetic acid concentrations in relation to sex and thyroid hormones among reproductive-aged men.

Sex and thyroid hormones are critical for male reproductive health. However, the associations between haloacetic acid (HAA) exposure - a known endocrine disruptor - and sex and thyroid hormones in humans remains unclear. We thus recruited 502 male participants seeking fertility evaluation from a reproductive center. We measured concentrations of sex and thyroid hormones in a single blood sample and dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) in repeated urine samples. Multivariable linear regression models were constructed to evaluate the associations between HAA concentrations and hormone measurements. After adjusting for potential confounders and urinary creatinine concentrations, urinary concentrations of TCAA were inversely associated with serum levels of sex hormone-binding globulin (SHBG), testosterone (T), T/luteinizing hormone ratio (T/LH), and thyroid stimulating hormone (TSH) (all P for trend < 0.10). Compared with participants in the lowest quartile of TCAA concentrations, those in the highest quartile had reduced serum levels of SHGB by 14.2 % (95% CI: -26.7, -3.0 %), T by 11.1 % (95% CI: -21.7, -1.3 %), T/LH by 21.0 % (95% CI: -36.7, -7.1 %), and TSH by 19.1 % (95% CI: -39.7, -1.5 %). Additionally, we observed inverse associations between continuous measurements of urinary HAAs and serum levels of free T, bioactive T, and estradiol. Our findings suggest that male HAA exposure may be associated with disrupted sex and thyroid function.

Prediction of additional hospital days in patients undergoing cervical spine surgery with machine learning methods.

BACKGROUND: Machine learning (ML), a subset of artificial intelligence (AI), uses algorithms to analyze data and predict outcomes without extensive human intervention. In healthcare, ML is gaining attention for enhancing patient outcomes. This study focuses on predicting additional hospital days (AHD) for patients with cervical spondylosis (CS), a condition affecting the cervical spine. The research aims to develop an ML-based nomogram model analyzing clinical and demographic factors to estimate hospital length of stay (LOS). Accurate AHD predictions enable efficient resource allocation, improved patient care, and potential cost reduction in healthcare. METHODS: The study selected CS patients undergoing cervical spine surgery and investigated their medical data. A total of 945 patients were recruited, with 570 males and 375 females. The mean number of LOS calculated for the total sample was 8.64 ± 3.7 days. A LOS equal to or <8.64 days was categorized as the AHD-negative group (n = 539), and a LOS > 8.64 days comprised the AHD-positive group (n = 406). The collected data was randomly divided into training and validation cohorts using a 7:3 ratio. The parameters included their general conditions, chronic diseases, preoperative clinical scores, and preoperative radiographic data including ossification of the anterior longitudinal ligament (OALL), ossification of the posterior longitudinal ligament (OPLL), cervical instability and magnetic resonance imaging T2-weighted imaging high signal (MRI T2WIHS), operative indicators and complications. ML-based models like Lasso regression, random forest (RF), and support vector machine (SVM) recursive feature elimination (SVM-RFE) were developed for predicting AHD-related risk factors. The intersections of the variables screened by the aforementioned algorithms were utilized to construct a nomogram model for predicting AHD in patients. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve and C-index were used to evaluate the performance of the nomogram. Calibration curve and decision curve analysis (DCA) were performed to test the calibration performance and clinical utility. RESULTS: For these participants, 25 statistically significant parameters were identified as risk factors for AHD. Among these, nine factors were obtained as the intersection factors of these three ML algorithms and were used to develop a nomogram model. These factors were gender, age, body mass index (BMI), American Spinal Injury Association (ASIA) scores, magnetic resonance imaging T2-weighted imaging high signal (MRI T2WIHS), operated segment, intraoperative bleeding volume, the volume of drainage, and diabetes. After model validation, the AUC was 0.753 in the training cohort and 0.777 in the validation cohort. The calibration curve exhibited a satisfactory agreement between the nomogram predictions and actual probabilities. The C-index was 0.788 (95% confidence interval: 0.73214-0.84386). On the decision curve analysis (DCA), the threshold probability of the nomogram ranged from 1 to 99% (training cohort) and 1 to 75% (validation cohort). CONCLUSION: We successfully developed an ML model for predicting AHD in patients undergoing cervical spine surgery, showcasing its potential to support clinicians in AHD identification and enhance perioperative treatment strategies.

Mapping global lake aquatic vegetation dynamics using 10-m resolution satellite observations.

Aquatic vegetation is crucial for improving water quality, supporting fisheries and preserving biodiversity in lakes. Monitoring the spatiotemporal dynamics of aquatic vegetation is indispensable for the assessment and protection of lake ecosystems. Nevertheless, a comprehensive global assessment of lacustrine aquatic vegetation is lacking. This study introduces an automatic identification algorithm (with a total accuracy of 94.4%) for Sentinel-2 MSI, enabling the first-ever global mapping of aquatic vegetation distribution in 1.4 million lakes using 14.8 million images from 2019 to 2022. Results show that aquatic vegetation occurred in 81,116 lakes across six continents over the past four years, covering a cumulative maximum aquatic vegetation area (MVA) of 16,111.8 km2. The global median aquatic vegetation occurrence (VO, in %) is 3.0%, with notable higher values observed in South America (7.4%) and Africa (4.1%) compared with Asia (2.7%) and North America (2.4%). High VO is also observed in lakes near major rivers such as the Yangtze, Ob, and Paraná Rivers. Integrating historical data with our calculated MVA, the aquatic vegetation changes in 170 lakes worldwide were analyzed. It shows that 72.4% (123/170) of lakes experienced a decline in aquatic vegetation from the early 1980s to 2022, encompassing both submerged and overall aquatic vegetation. The most substantial decrease is observed in Asia and Africa. Our findings suggest that, beyond lake algal blooms and temperature, the physical characteristics of the lakes and their surrounding environments could also influence aquatic vegetation distribution. Our research provides valuable information for the conservation and restoration of lacustrine aquatic vegetation.

Establishment and validation of nomogram model for predicting major adverse cardiac events in patients with acute ST-segment elevation myocardial infarction based on glycosylated hemoglobin A1c to apolipoprotein A1 ratio: An observational study.

The objective of the current study is to assess the usefulness of HbA1cAp ratio in predicting in-hospital major adverse cardiac events (MACEs) among acute ST-segment elevation myocardial infarction (STEMI) patients that have undergone percutaneous coronary intervention (PCI). Further, the study aims to construct a ratio nomogram for prediction with this ratio. The training cohort comprised of 511 STEMI patients who underwent emergency PCI at the Huaibei Miners' General Hospital between January 2019 and May 2023. Simultaneously, 384 patients treated with the same strategy in First People's Hospital of Hefei formed the validation cohort during the study period. LASSO regression was used to screen predictors of nonzero coefficients, multivariate logistic regression was used to analyze the independent factors of in-hospital MACE in STEMI patients after PCI, and nomogram models and validation were established. The LASSO regression analysis demonstrated that systolic blood pressure, diastolic blood pressure, D-dimer, urea, and glycosylated hemoglobin A1c (HbA1c)/apolipoprotein A1 (ApoA1) were significant predictors with nonzero coefficients. Multivariate logistic regression analysis was further conducted to identify systolic blood pressure, D-dimer, urea, and HbA1c/ApoA1 as independent factors associated with in-hospital MACE after PCI in STEMI patients. Based on these findings, a nomogram model was developed and validated, with the C-index in the training set at 0.77 (95% CI: 0.723-0.817), and the C-index in the validation set at 0.788 (95% CI: 0.734-0.841), indicating excellent discrimination accuracy. The calibration curves and clinical decision curves also demonstrated the good performance of the nomogram models. In patients with STEMI who underwent PCI, it was noted that a higher HbA1c of the ApoA1 ratio is significantly associated with in-hospital MACE. In addition, a nomogram is constructed having considered the above-mentioned risk factors to provide predictive information on in-hospital MACE occurrence in these patients. In particular, this tool is of great value to the clinical practitioners in determination of patients with a high risk.

Ion cocktail therapy for myocardial infarction by synergistic regulation of both structural and electrical remodeling.

Myocardial infarction (MI) is a leading cause of death worldwide. Few drugs hold the ability to depress cardiac electrical and structural remodeling simultaneously after MI, which is crucial for the treatment of MI. The aim of this study is to investigate an effective therapy to improve both electrical and structural remodeling of the heart caused by MI. Here, an "ion cocktail therapy" is proposed to simultaneously reverse cardiac structural and electrical remodeling post-MI in rats and minipigs by applying a unique combination of silicate, strontium (Sr) and copper (Cu) ions due to their specific regulatory effects on the behavior of the key cells involved in MI including angiogenesis of endothelial cells, M2 polarization of macrophages and apoptosis of cardiomyocyte. The results demonstrate that ion cocktail treatment attenuates structural remodeling post-MI by ameliorating infarct size, promoting angiogenesis in both peri-infarct and infarct areas. Meantime, to some extent, ion cocktail treatment reverses the deteriorative electrical remodeling by reducing the incidence rate of early/delayed afterdepolarizations and minimizing the heterogeneity of cardiac electrophysiology. This ion cocktail therapy reveals a new strategy to effectively treat MI with great clinical translation potential due to the high effectiveness and safety of the ion cocktail combination.

Preservation of Topological Surface States in Millimeter-Scale Transferred Membranes.

Ultrathin topological insulator membranes are building blocks of exotic quantum matter. However, traditional epitaxy of these materials does not facilitate stacking in arbitrary orders, while mechanical exfoliation from bulk crystals is also challenging due to the non-negligible interlayer coupling therein. Here we liberate millimeter-scale films of the topological insulator Bi2Se3, grown by molecular beam epitaxy, down to 3 quintuple layers. We characterize the preservation of the topological surface states and quantum well states in transferred Bi2Se3 films using angle-resolved photoemission spectroscopy. Leveraging the photon-energy-dependent surface sensitivity, the photoemission spectra taken with 6 and 21.2 eV photons reveal a transfer-induced migration of the topological surface states from the top to the inner layers. By establishing clear electronic structures of the transferred films and unveiling the wave function relocation of the topological surface states, our work lays the physics foundation crucial for the future fabrication of artificially stacked topological materials with single-layer precision.

Overexpression of phosphatidylserine synthase IbPSS1 enhances salt tolerance by stimulating ethylene signaling-dependent lignin synthesis in sweetpotato roots.

Phosphatidylserine (PS) is an important lipid signaling required for plant growth regulation and salt stress adaptation. However, how PS positively regulate plant salt tolerance is still largely unknown. In this study, IbPSS1-overexpressed sweetpotato plants that exhibited overproduction of PS was employed to explore the mechanisms underlying the PS stimulation of plant salt tolerance. The results revealed that the IbPSS1-overexpressed sweetpotato accumulated less Na+ in the stem and leaf tissues compared with the wild type plants. Proteomic profile of roots showed that lignin synthesis-related proteins over-accumulated in IbPSS1-overexpressed sweetpotato. Correspondingly, the lignin content was enhanced but the influx of Na + into the stele was significantly blocked in IbPSS1-overexpressed sweetpotato. The results further revealed that ethylene synthesis and signaling related genes were upregulated in IbPSS1-overexpressed sweetpotato. Ethylene imaging experiment revealed the enhancement of ethylene mainly localized in the root stele. Inhibition of ethylene synthesis completely reversed the PS-overproduction induced lignin synthesis and Na+ influx pattern in stele tissues. Taken together, our findings demonstrate a mechanism by which PS regulates ethylene signaling and lignin synthesis in the root stele, thus helping sweetpotato plants to block the loading of Na+ into the xylem and to minimize the accumulation of Na+ in the shoots.

CircSCNN1A inhibits the proliferation, migration and invasion of renal cell carcinoma cells by decreasing CLDN8 expression through miR-590-5p.

BACKGROUND: Increasing evidence suggests that circular RNA (circRNA) plays a regulatory role in the progression of renal cell carcinoma (RCC). However, the precise function and underlying mechanism of circSCNN1A in RCC progression still remain unclear. METHODS: The expression levels of circSCNN1A, microRNA-590-5p (miR-590-5p), claudin 8 (CLDN8), cyclin D1, matrix metalloprotein 2 (MMP2), MMP9, E-cadherin, N-cadherin and vimentin were detected by a quantitative real-time polymerase chain reaction and Western blotting analysis. Immunohistochemistry assay was performed to analyze the positive expression rate of CLDN8. Cell proliferation was investigated by cell colony formation, 5-Ethynyl-2'-deoxyuridine and DNA content quantitation assays. Cell migration and invasion were assessed by wound-healing and transwell invasion assays. Interactions among circSCNN1A, miR-590-5p and CLDN8 were identified by dual-luciferase reporter assay, RNA immunoprecipitation assay and RNA pull-down assay. Xenograft mouse model assay was conducted to verify the effect of circSCNN1A on tumor formation in vivo. RESULTS: CircSCNN1A and CLDN8 expression were significantly downregulated, while miR-590-5p was upregulated in both RCC tissues and cells. CircSCNN1A overexpression inhibited RCC cell proliferation, migration and invasion, accompanied by decreases of cyclin D1, MMP2, MMP9, N-cadherin and vimentin expression and an increase of E-cadherin expression. CircSCNN1A acted as a miR-590-5p sponge and regulated RCC cell processes by binding to miR-590-5p. CLDN8, a target gene of miR-590-5p, was involved in the regulation of the biological behaviors of RCC cells by miR-590-5p. In addition, circSCNN1A induced CLDN8 production by interacting with miR-590-5p. Further, circSCNN1A suppressed tumor formation in vivo. CONCLUSION: CircSCNN1A inhibited RCC cell proliferation, migration and invasion by regulating the miR-590-5p/CLDN8 pathway.

Preparation of Rehmanniae Radix Praeparata Polysaccharide Iron(III) Complex and Evaluation of Its Biological Activity.

This study extracted and purified a polysaccharide from Rehmanniae radix praeparata (RGP) with an average molecular weight. The structural characteristics of RGP and its iron (III) complex, RGP-Fe(III), were examined for their antioxidant properties and potential in treating iron deficiency anemia (IDA). Analysis revealed that RGP comprised Man, Rha, Gal, and Xyl, with a sugar residue skeleton featuring 1→3; 1→2, 3; and 1→2, 3, 4 linkages, among others. RGP-Fe(III) had a molecular weight of 4.39×104 Da. Notably, RGP-Fe(III) exhibited superior antioxidant activity compared to RGP alone. In IDA rat models, treatment with RGP-Fe(III) led to increased weight gain, restoration of key blood parameters including hemoglobin, red blood cells, and mean hemoglobin content, elevated serum iron levels, and decreased total iron-binding capacity. Histological examination revealed no observable toxic effects of RGP-Fe(III) on the liver and spleen. These findings suggest the potential of RGP-Fe(III) as a therapeutic agent for managing IDA and highlight its promising antioxidant properties.

Comparison of children and adults in deep brain stimulation for Tourette Syndrome: a large-scale multicenter study of 102 cases with long-term follow-up.

BACKGROUND: Deep brain stimulation (DBS) is a promising therapy for refractory Gilles de la Tourette syndrome (GTS). However, its long-term efficacy, safety, and recommended surgical age remain controversial, requiring evidence to compare different age categories. METHODS: This retrospective cohort study recruited 102 GTS patients who underwent DBS between October 2006 and April 2022 at two national centers. Patients were divided into two age categories: children (aged < 18 years; n = 34) and adults (aged ≥ 18 years; n = 68). The longitudinal outcomes as tic symptoms were assessed by the YGTSS, and the YBOCS, BDI, and GTS-QOL were evaluated for symptoms of obsessive-compulsive disorder (OCD), depression, and quality of life, respectively. RESULTS: Overall, these included patients who finished a median 60-month follow-up, with no significant difference between children and adults (p = 0.44). Overall, the YGTSS total score showed significant postoperative improvements and further improved with time (improved 45.2%, 51.6%, 55.5%, 55.6%, 57.8%, 61.4% after 6, 12, 24, 36, 48, and ≥ 60 months of follow-up compared to baseline, respectively) in all included patients (all p < 0.05). A significantly higher improvement was revealed in children than adults at ≥ 60 months of follow-up in the YGTSS scores (70.1% vs 55.9%, p = 0.043), and the time to achieve 60% improvement was significantly shorter in the children group (median 6 months vs 12 months, p = 0.013). At the last follow-up, the mean improvements were 45.4%, 48.9%, and 55.9% and 40.3%, 45.4%, and 47.9% in YBOCS, BDI, and GTS-QOL scores for children and adults, respectively, which all significantly improved compared to baseline (all p < 0.05) but without significant differences between these two groups (all p > 0.05), and the children group received significantly higher improvement in GTS-QOL scores than adults (55.9% vs. 47.9%, p = 0.049). CONCLUSIONS: DBS showed acceptable long-term efficacy and safety for both children and adults with GTS. Surgeries performed for patients younger than 18 years seemed to show acceptable long-term efficacy and safety and were not associated with increased risks of loss of benefit compared to patients older than 18 at the time of surgery. However, surgeries for children should also be performed cautiously to ensure their refractoriness and safety.

Gestational Exposure to PM2.5 and Specific Constituents, Meconium Metabolites, and Neonatal Neurobehavioral Development: A Cohort Study.

Exposure to fine particulate matter (PM2.5) during pregnancy has been inversely associated with neonatal neurological development. However, the associations of exposure to specific PM2.5 constituents with neonatal neurological development remain unclear. We investigated these associations and examined the mediating role of meconium metabolites in a Chinese birth cohort consisting of 294 mother-infant pairs. Our results revealed that exposure to PM2.5 and its specific constituents (i.e., organic matter, black carbon, sulfate, nitrate, and ammonium) in the second trimester, but not in the first or third trimester, was inversely associated with the total neonatal behavioral neurological assessment (NBNA) scores. The PM2.5 constituent mixture in the second trimester was also inversely associated with NBNA scores, and sulfate was identified as the largest contributor. Furthermore, meconium metabolome analysis identified four metabolites, namely, threonine, lysine, leucine, and saccharopine, that were associated with both PM2.5 constituents and NBNA scores. Threonine was identified as an important mediator, accounting for a considerable proportion (14.53-15.33%) of the observed inverse associations. Our findings suggest that maternal exposure to PM2.5 and specific constituents may adversely affect neonatal behavioral development, in which meconium metabolites may play a mediating role.