Transforming growth factor-beta 1 enhances discharge activity of cortical neurons.

JOURNAL/nrgr/04.03/01300535-202502000-00031/figure1/v/2024-05-28T214302Z/r/image-tiff Transforming growth factor-beta 1 (TGF-ß1) has been extensively studied for its pleiotropic effects on central nervous system diseases. The neuroprotective or neurotoxic effects of TGF-ß1 in specific brain areas may depend on the pathological process and cell types involved. Voltage-gated sodium channels (VGSCs) are essential ion channels for the generation of action potentials in neurons, and are involved in various neuroexcitation-related diseases. However, the effects of TGF-ß1 on the functional properties of VGSCs and firing properties in cortical neurons remain unclear. In this study, we investigated the effects of TGF-ß1 on VGSC function and firing properties in primary cortical neurons from mice. We found that TGF-ß1 increased VGSC current density in a dose- and time-dependent manner, which was attributable to the upregulation of Nav1.3 expression. Increased VGSC current density and Nav1.3 expression were significantly abolished by preincubation with inhibitors of mitogen-activated protein kinase kinase (PD98059), p38 mitogen-activated protein kinase (SB203580), and Jun NH2-terminal kinase 1/2 inhibitor (SP600125). Interestingly, TGF-ß1 significantly increased the firing threshold of action potentials but did not change their firing rate in cortical neurons. These findings suggest that TGF-ß1 can increase Nav1.3 expression through activation of the ERK1/2-JNK-MAPK pathway, which leads to a decrease in the firing threshold of action potentials in cortical neurons under pathological conditions. Thus, this contributes to the occurrence and progression of neuroexcitatory-related diseases of the central nervous system.

Gamma-glutamyl transferase 5 overexpression in cerebrovascular endothelial cells improves brain pathology, cognition, and behavior in APP/PS1 mice.

JOURNAL/nrgr/04.03/01300535-202502000-00030/figure1/v/2024-05-28T214302Z/r/image-tiff In patients with Alzheimer's disease, gamma-glutamyl transferase 5 (GGT5) expression has been observed to be downregulated in cerebrovascular endothelial cells. However, the functional role of GGT5 in the development of Alzheimer's disease remains unclear. This study aimed to explore the effect of GGT5 on cognitive function and brain pathology in an APP/PS1 mouse model of Alzheimer's disease, as well as the underlying mechanism. We observed a significant reduction in GGT5 expression in two in vitro models of Alzheimer's disease (Aß1-42-treated hCMEC/D3 and bEnd.3 cells), as well as in the APP/PS1 mouse model. Additionally, injection of APP/PS1 mice with an adeno-associated virus encoding GGT5 enhanced hippocampal synaptic plasticity and mitigated cognitive deficits. Interestingly, increasing GGT5 expression in cerebrovascular endothelial cells reduced levels of both soluble and insoluble amyloid-ß in the brains of APP/PS1 mice. This effect may be attributable to inhibition of the expression of ß-site APP cleaving enzyme 1, which is mediated by nuclear factor-kappa B. Our findings demonstrate that GGT5 expression in cerebrovascular endothelial cells is inversely associated with Alzheimer's disease pathogenesis, and that GGT5 upregulation mitigates cognitive deficits in APP/PS1 mice. These findings suggest that GGT5 expression in cerebrovascular endothelial cells is a potential therapeutic target and biomarker for Alzheimer's disease.

Exogenous paths regulate electron transfer enhancing sediment phosphorus immobilization.

The lack of electron acceptors in anaerobic sediments leads to endogenous phosphorus release and low removal efficiency of organic pollutants. This study introduced electrodes and iron oxides into sediments to construct electron network transport chains to supplement electron acceptors. The sediment total organic carbon (TOC) removal efficiencies of closed-circuit (CC) and closed-circuit with Fe addition (CC-Fe) were estimated to be 1.4 and 1.7 times of the control. Unlike the fluctuation of phosphorus in the overlying water of the controls, the CC-Fe was stabled at 0.04-0.08 mg/L during the 84-d operation. The phosphorus in interstitial water of CC-Fe was 30 % less than in control, whereas in sediment, the redox sensitive phosphorus was increased by 14 %, indicating phosphorus was preferred to fix into sediments rather than interstitial water. This is important to reduce the risk of endogenous phosphorus returning to the overlying water. Microbial community analysis showed that the multiplication of Fonticella in CC-Fe (20 %) was 1.8-fold of control (11 %) which improved the TOC removal efficiency. While electroactive microorganisms accumulated near the electrode reduced the abundance of Fe-reducing bacteria, such as Desulfitobacterium (2.4 %), leading to better phosphorus fixation. These findings suggest a strategy for the efficient bioremediation of endogenous pollution in water, with broader implications for regulating electron transport paths and element cycles in aquatic environments.

A high-efficiency and durable flame retardant for cotton fabrics: Ammonium ethyl acryloylphosphoramidate.

The ammonium ethyl acryloylphosphoramidate (AEA) was synthesized by acrylamide, ethanolamine, and phosphorus oxychloride; the nuclear magnetic resonance (NMR) and Fourier transform infrared spectroscopy (FTIR) were applied to analyze the structure of AEA molecule. Using the dip-cure process to treat raw cotton (RC) with AEA flame retardant, the finished fabric had excellent flame retardancy. The cone calorimeter, thermogravimetric, FTIR, and vertical flame tests illustrated finished fabrics underwent synergistic and condensed-phase flame retardation. The finished fabric also had excellent durability, and the higher the sealing degree of phosphorus atoms, the higher the durability. The limiting oxygen index (LOI) of RC-AEA3-20 (raw cotton finished with 20 wt% AEA3) reached 45.4 %. However, the LOI only dropped to 34.9 % after 50 laundering cycles under the AATCC 61-2013 3 A standard. The excellent durability and FTIR analyses of finished fabrics suggested that the -N-P(=O)-O-C- covalent bond was formed between flame retardant and cellulose. This covalent bond exhibited a p-π conjugation effect, enhancing the stability of -N-P(=O)-O-C- bond, improving the durability of finished fabrics. In conclusion, adding reactive groups into flame retardants, like CH2=CH- and -N-P(=O)-O-NH4+, could increase the durability of finished cotton fabrics.

A comprehensive foodomics analysis of rambutan seed oils: Focusing on the physicochemical parameters, lipid concomitants and lipid profiles.

A foodomics approach was employed to systematically characterize and compare the quality parameters, antioxidant activity, minor-components, fatty acid composition, and lipid profiles of the seed oils from the three most popular rambutan varieties in China. The total lipid content ranged from 23.40 to 25.77 g/100 g. The fatty acids 9cC18:1 (39.84%-40.92%) and C20:0 (28.45%-30.23%) were identified as the dominant ones, which are uncommon among higher plants. All oil samples exhibited low AI and TI values. BR-7 exhibited the highest levels of squalene (21.48 mg/kg), cholesterol (144.43 mg/kg), and tocopherol (17.42 mg/kg), and the lowest levels of polyphenols (24.21 mg GAE/kg). Additionally, a total of 807 lipid species were identified, with TAG, DGTS, and PE being the predominant ones. Multivariate statistical analyses revealed significant variations in lipid profiles among the varieties, particularly in glycerophospholipids and sphingolipids. Fifty-seven distinct lipids were identified as potential markers for distinguishing between rambutan varieties. Furthermore, a hypothetical scenario was developed by linking relevant lipid metabolism pathways. These findings establish a theoretical framework for comprehending rambutan seed oil in depth and unlocking its high-value potential.

Associations of Tooth loss with Risk of All-cause and Cause-specific Mortality Among US Adults with Diabetes mellitus.

OBJECTIVES: To determine whether tooth loss affects all-cause and cause-specific mortality in a nationally representative sample of adults with diabetes mellitus (DM) in the United States. METHODS: This prospective cohort study involved 8,207 participants aged 30 years or older at baseline, all diagnosed with diabetes mellitus and enrolled in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018. Tooth loss was stratified into 28 teeth (complete), 20-27 teeth (tooth loss), 9-19 teeth (lacking functional), 1-8 teeth (severe tooth loss) and edentulism. To estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and specific-cause mortality in diabetes mellitus participants according to tooth loss, multivariate cox proportional hazards regression models were used. Relationships between mortality and quartiles of mean tooth loss levels were analyzed, with the lowest quartile as the baseline for comparisons. RESULTS: During a median of 6.92 years of follow-up, 2,317 deaths were documented. After multivariate adjustments, higher tooth loss levels were significantly and non-linearly associated with higher risks of all-cause, CVD-related and DM-related mortality among participants with DM. When compared with the reference group of mean tooth loss levels, the highest quartile showed significantly increased risks: all-cause mortality (HR, 2.11; 95% CI, 1.53-2.91, P-trend < 0.001), CVD-related mortality (HR, 3.24, 95% CI, 1.54-6.85, P-trend < 0.001) and DM-related mortality (HR, 2.78, 95% CI, 1.15-6.68, P-trend < 0.001). CONCLUSIONS: Tooth loss is associated with an increased risk of all-cause, CVD-related and diabetes mellitus mortality among adults with diabetes mellitus in the US.

Incidence of medical device-related pressure injuries: a meta-analysis.

BACKGROUND: Medical device-related pressure injures (MDRPIs) are common in critically ill patients and associated with negative clinical outcomes and elevated healthcare expenses. We aim to estimate worldwide incidence of MDRPI and explore associated factors through systemic review and meta-analysis. METHODS: The PubMed, Web of Science, Cochrane Library, and Ovid EMBASE databases were systematically queried to identify relevant studies published from Jan 1, 2010 up until June 30, 2024. Studies were included if they provided data on the incidence or prevalence of MDRPI. Random-effect models were utilized to calculate the overall or domain-specific aggregated estimates of MDRPI. A meta-regression analysis was additionally performed to investigate the heterogeneity among studies. RESULTS: We included 28 observational studies on 117,624 patients in the meta-analysis. The overall incidence of MDRPI was 19.3% (95% confidence interval (CI) 13.5-25.2%). The incidence of MDRPI in Europe, North America, Asia, South America, and Oceania was 17.3% (95% CI 12.7-21.9%), 3.6% (95% CI 0.0-8.5%), 21.9% (95% CI 14.3-29.6%), 48.3% (95% CI 20.8-75.7%), and 13.0% (95% CI 5.0-21.1%), respectively (p < 0.01). Multivariate meta-regressions revealed South America and special inpatient (critically ill patient, etc.) were independently associated with higher MDRPI incidence. CONCLUSIONS: Nearly, 20% of the patients in ICU suffered from MDRPI. The incidence of MDRPI in underdeveloped regions is particularly concerning, highlighting the importance of focusing on measures to prevent it, in order to reduce the medical burden and enhance the quality of life for affected patients.

qPrimerDB 2.0: an updated comprehensive gene-specific qPCR primer database for 1172 organisms.

High-quality primer design is essential for the success of all polymerase chain reaction (PCR)-based experiments. We previously developed a thermodynamics-based gene-specific quantitative PCR (qPCR) primer database for 147 organisms, which has been used extensively in gene expression studies. However, the number of organisms and the imperfection of function in the database limits its potential applications. Here, we improved the functionality of qPrimerDB to create a more comprehensive primer resource. Specifically, we (i) developed an improved primer design tool, qPrimer, building upon the previous qPrimerDB pipeline, to enhance the efficiency and simplicity of genome-scale qPCR primer design; (ii) pre-computed qPCR primer resources from 1 308 genomes of 1172 organisms and (iii) introduced a complete system for identifying, designing, checking, marking, and submitting qPCR primers. qPrimerDB 2.0 is freely available at https://qprimerdb.biodb.org. The qPrimer source code is available at https://github.com/swu1019lab/qPrimer.

Role of the circRNA_34414/miR-6960a-5p/SIRT3 axis in postoperative delirium via CA1 Vglut1+ neurons in older mice.

AIMS: Postoperative delirium (POD) is a common neurological complication in elderly patients after anesthesia/surgery. The main purpose of this study is to explore the effect of circRNA-targeted miRNA regulating SIRT3 on mitochondrial function through ceRNA mechanism under the surgical model of tibial fracture and to further explore the potential mechanism of postoperative delirium mediated by circRNA, so as to provide new ideas for clinical diagnosis and prevention of POD. METHODS: The surgical model of tibial fracture under sevoflurane anesthesia caused acute delirium-like behavior in elderly mice. We observed that the decrease of SIRT3 and mitochondrial dysfunction was related to POD, and miRNA and circRNA (circRNA_34414) related to SIRT3 were further studied. Through luciferase and RAP, we observed that circRNA_34414, as a miRNA sponge, was involved in the regulation of SIRT3 expression. RESULTS: Postoperative delirium in elderly mice showed decreased expression of hippocampal circRNA_34414, increased expression of miR-6960-5p, decreased expression of SIRT3, and impaired mitochondrial membrane potential. Overexpression of circRNA_34414, or knockdown of miR-6960-5p, or overexpression of SIRT3 in hippocampal CA1 glutamatergic neurons significantly upregulated hippocampal SIRT3 expression, increased mitochondrial membrane potential levels, and significantly ameliorated postoperative delirium in aged mice; CircRNA_34414 ameliorates postoperative delirium in mice, possibly by targeting miR-6960-5p to upregulate SIRT3. CONCLUSIONS: CircRNA_34414 is involved in the improvement of postoperative delirium induced by anesthesia/surgery by upregulating SIRT3 via sponging miR-6960-5p.

Properties, evaluation and application of naringin magnetic molecularly imprinted polymer based on synergistic imprinting strategy.

A novel and facile surface molecularly imprinted polymer coated on magnetic chitosan (Fe3O4@CS@MIP) was fabricated for the selective recognition and enrichment of naringin (NRG). The Fe3O4@CS@MIP was prepared based on covalent-noncovalent synergistic imprinting strategies, utilizing 4-vinyl phenyl boric acid as covalent functional monomer, deep eutectic solvent (choline chloride/methacrylic acid [ChCl/MAA]) as non-covalent functional monomer and Fe3O4@CS nanoparticles as the magnetic support. The obtained Fe3O4@CS@MIP exhibited a uniform morphology, excellent crystallinity, outstanding magnetic properties, and high surface area. Owing to the double recognition abilities, the resultant polymer showed exceptional binding performance and rapid mass transfer in phosphate buffer (pH 7.0). The maximum binding amount of Fe3O4@CS@MIP was found to be 15.08 mg g-1, and the equilibrium adsorption could be achieved within 180 min. Moreover, they also exhibited stronger selectivity for NRG and satisfactory reusability, with only 11.0% loss after five adsorption-desorption cycles. Additionally, the Fe3O4@CS@MIP, serving as an adsorbent, presented practical application potential in the separation and enrichment of NRG from pummelo peel, with extraction efficiency in the range of 79.53% to 84.63%. This work provided a new strategy for improving the performance of MIP and contributed an attractive option for the extraction of NRG in complex samples.

Characteristics and Genesis of Carbonate Weathering Crust Reservoirs: A Case from the Ma5Member of Ordovician in Gaoqiao Area, Ordos Basin, China.

The hydrocarbon reserves in carbonate rocks account for about half of the global hydrocarbon reserves and are an important reservoir type. The Ordovician Majiagou Formation in the central Ordos Basin is a representative weathering crust reservoir. The Caledonian movement uplifted the stratum as a whole, and subsequently, 120 million years of exposed weathering, denudation, and leaching created this unique karst paleomorphology. Dolomite reservoirs have developed dissolved pores and microfractures, which are the best reserved spaces for natural gas and good hydrocarbon migration channels. This paper takes the Ma5Member (hereinafter referred to as Ma51+2) carbonate reservoir in Gaoqiao Gas Field as the research target, based on the core, thin section, cathodoluminescence, logging data, etc., and systematically study the effect of karstification on the reservoir and the genesis of the dolomite reservoir. The results show that the depositional period of the Ordovician Majiagou strata is a regression cycle and the depositional environment is a limited evaporative tidal flat. The reservoir lithology of Ma51+2 is mainly gypsiferous dolomite and micrite dolomite. The reservoir space types consist of intergranular pores, gypsum mold pore, intragranular dissolution pores, intercrystalline pores, and microfractures. The porosity has values from 0.3 to 11.2% (mostly less than 5.0%) with an average of 3.3%, and the permeability ranges from 0.003 to 13.2 mD (mostly less than 1 mD) with an average of 0.36 mD. Karstification is divided into three periods, including syngenetic karst, eogenetic karst, and burial karst. The sedimentary microfacies determine the material basis of the reservoir, and multistage karstification finally modifies the physical properties. By deeply exploring the formation mechanism and influencing factors of the carbonate reservoir in the Ordovician Majiagou Formation, it provides an important theoretical basis and practical guidance for oil and gas exploration and development. At the same time, it also has important reference value for understanding and predicting the development law and distribution characteristics of carbonate reservoirs under similar geological background.

The long-term outcomes in drug-resistant epilepsy patients who underwent subtotal hemispherotomy: A single-center retrospective cohort study.

OBJECTIVE: To evaluate the long-term outcomes of subtotal hemispherotomy (SH) in treating drug-resistant epilepsy caused by unilateral hemispheric lesions and try to give the prognostic factors for these outcomes. METHODS: We retrospectively reviewed the clinical data of 19 patients who underwent SH in Sanbo Brain Hospital, Capital Medical University, Beijing, China, from May 2008 to April 2021. All clinical data and factors related to surgical and functional outcomes, including motor, neuropsychiatric, and language function, were collected and analyzed. RESULTS: The surgical outcomes showed 13 (68 %) patients were seizure-free at the last follow-up (2-14 years, mean: 5.6±2.9). No changes were found in motor outcomes in 12 (63 %) patients; seven (37 %) patients had new permanent motor deficits (NPMD). Improvement in the full-scale intelligence quotient (FIQ) (p = 0.009) was observed. Univariate analysis found that patients who did not achieve seizure freedom had a significantly older age at surgery (p = 0.017) and acute post-operative seizures (APOS) (p = 0.046). Kaplan-Meier analysis also identified significant differences in seizure outcomes between the children and adult subgroups (p = 0.0017). Multivariate Cox analysis showed that older age at surgery (HR=1.055, p = 0.034) was associated with shorter time-to-seizure-recurrence. Resection of the central operculum and insula (OR= 80.433, p =0.031) and higher monthly seizure frequency (OR= 1.073, p = 0.040) were also poor prognostic factors for motor function outcomes. CONCLUSION: SH is an effective treatment procedure in treating patients with drug-resistant epilepsy caused by hemispheric lesions with satisfied seizure outcomes, limited impairment of motor function, and preserving neuropsychiatric outcomes.

Coordination of miR319-TaPCF8 with TaSPL14 orchestrates auxin signaling and biosynthesis to regulate plant height in common wheat.

Wheat culms, comprising four to six internodes, are critically involved in determining plant height and lodging resistance, essential factors for field performance and regional adaptability. This study revealed the regulatory function of miR319 in common wheat plant height. Repression of tae-miR319 through short tandem target mimics (STTM) caused an increased plant height, while overexpression (OE) of tae-miR319 had the opposite effect. Overexpressing a miR319-resistant target gene TaPCF8 (rTaPCF8), increased plant height. TaPCF8 acted as a transcription repressor of downstream genes TaIAAs, which interact physically with TaSPL14. The significant differences of indole-3-acetic acid (IAA) contents indicate the involvement of auxin pathway in miR319-mediated plant height regulation. Finally, we identified two TaPCF8 haplotypes in global wheat collections. TaPCF8-5A-Hap2, as per association and evolution examinations, was subjected to strong substantial selection throughout wheat breeding. This haplotype, associated with shorter plant height, aligns with global breeding requirements. Consequently, in high-yield wheat breeding, we proposed a potential molecular marker for marker-assisted selection (MAS). Our findings offer fresh perspectives into the molecular mechanisms that underlie the miR319-TaPCF8 module's regulation of plant height by orchestrating auxin signaling and biosynthesis in wheat.

The clinical characteristics analysis of serum markers for the cardiovascular system in early-stage COVID-19 patients.

Background: This study aimed to investigate alterations in serum markers [creatine kinase-MB (CKMB), cardiac troponin T (cTnT), myoglobin (Myo), B-type natriuretic peptide (BNP), D-dimer (DD), procalcitonin (PCT) and interleukin-6 (IL6)] in early Omicron variant infection and analyzed their correlation with clinical parameters. Methods: Retrospective analysis of 1,138 mild/asymptomatic cases at Tianjin First Central Hospital, including age, gender, serum markers and nucleic acid test results. Statistical analysis used SPSS software, version 24.0. Results: Elevated cTnT, BNP (125-400), and DD (0.55-1.10) levels were prevalent at 12.92%, 15.64%, and 14.50%, respectively. Females had significantly higher proportions with slightly elevated BNP (19.34%) and DD (19.69%) levels. Patients over 35 had a higher proportion of slight elevation in BNP (20.00%). Abnormal levels of serum markers were significantly associated with older age, increased PCT and IL6 levels, as well as delayed nucleic acid clearance. Additionally, levels of immunoglobulin G (IgG) were notably reduced in these cases. Patients with prolonged nucleic acid clearance (>14 days) had higher BNP and DD levels upon admission. Logistic regression identified PCT (OR = 237.95) as the most significant risk factor for abnormal serum markers for cardiovascular system injury. Conclusion: Early Omicron infection might do subclinical damage to the cardiovascular system. Elevated cTnT, BNP and DD levels were correlated with age, gender, inflammatory factors, and IgG. Notably, high PCT level emerged as the most robust predictor of abnormal serum biomarkers.

Prenatal Diagnosis of Persistent Left Superior Vena Cava Using High-Definition Flow Render Mode and Spatiotemporal Image Correlation.

OBJECTIVE: This study aimed to assess the use of two-dimensional (2D) ultrasound combined with high-definition flow (HD-flow) render mode and spatiotemporal image correlation (STIC) in diagnosing and classifying fetal persistent left superior vena cava (PLSVC). METHODS: Overall, 114 cases of fetal PLSVC were diagnosed using 2D ultrasound combined with STIC, and 114 normal fetuses of the same gestational week were selected. These cases were retrospectively analyzed to evaluate the effectiveness of the diagnostic approach. RESULTS: All 114 PLSVC cases were diagnosed using 2D ultrasound combined with STIC. Although the diagnostic coincidence rate of PLSVC in the HD-flow combined with STIC was similar to that in the 2D ultrasound combined with HD-flow (96.8 vs 96.2%), 2D ultrasound with STIC enabled dynamic visualization of the PLSVC, furthering prenatal diagnosis. These cases were classified as type I PLSVC: 80 cases of type Ia, 29 cases of type Ib, and 5 cases of type Ic. Seventy isolated PLSVC cases (61.4%) were noted, whereas 44 cases (35.6%) were associated with concomitant structural abnormalities. Intracardiac structural malformations accounted for the highest proportion (n = 53, 58.89%), followed by single umbilical artery and facial/bodily abnormalities (n = 10, 11.11%). CONCLUSION: Combining HD-flow and STIC complements 2D ultrasound in diagnosing and classifying fetal PLSVC, demonstrating significant clinical relevance.

Reduction in renal interstitial fibrosis in aged male mice by intestinal microbiota rejuvenation.

INTRODUCTION: Renal interstitial fibrosis is an important pathological basis for kidney ageing and the progression of ageing nephropathy. In the present research, we established an aged mouse model of faecal microbiota transplantation (FMT), identified the rejuvenation features of the kidney in aged male mice, and preliminarily analysed the possible mechanism by which the rejuvenation of the intestinal microbiota reduces renal interstitial fibrosis and delays senescence in aged male mice. METHODS: We established an aged male mice model that was treated with FMT (FMT-Old) and a normal aged male mice control group (Old). Differentially expressed cytokines were identified using a cytokine array, and changes in protein expression related to signal transduction pathways in renal tissues were detected using a signalling pathway array. Senescence-associated ß-galactosidase and Masson staining were performed to observe the degrees of renal senescence and tubule interstitial fibrosis. Immunohistochemistry was utilized to detect changes in the expression of the ageing markers p53 and p21 and the inflammation-related protein nuclear factor (NF) κB p65 subunit (RelA/p65). RESULTS: The pathological features of renal senescence in the FMT-Old group were significantly alleviated, and the levels of the ageing indicators p53 and p21 were decreased (P < 0.05). Integrated predictive analysis revealed that six differentially expressed cytokines, macrophage inflammatory protein-3 beta (MIP-3ß or CCL-19), E-selectin, Fas ligand, C-X-C motif chemokine 11 (CXCL-11 or I-TAC), CXCL-1 (keratinocyte-derived chemokine), and CCL-3 (MIP-1α) were related to a common upstream regulatory protein, RelA/p65, and the expression of this protein was significantly different between groups according to the signalling pathway array. CONCLUSION: Our findings suggest that the intestinal microbiota regulates the renal microenvironment by reducing immune inflammatory responses through the inhibition of the NF-κB signalling pathway, thereby delaying renal senescence in aged male mice.

Identification and Validation of Aging Related Genes Signature in Chronic Obstructive Pulmonary Disease.

PURPOSE: Chronic Obstructive Pulmonary Disease (COPD) is regarded as an accelerated aging disease. Aging-related genes in COPD are still poorly understood. METHOD: Data set GSE76925 was obtained from the Gene Expression Omnibus (GEO) database. The "limma" package identified the differentially expressed genes. The weighted gene co-expression network analysis (WGCNA) constructes co-expression modules and detect COPD-related modules. The least absolute shrinkage and selection operator (LASSO) and the support vector machine recursive feature elimination (SVM-RFE) algorithms were chosen to identify the hub genes and the diagnostic ability. Three external datasets were used to identify differences in the expression of hub genes. Real-time reverse transcription polymerase chain reaction (RT-qPCR) was used to verify the expression of hub genes. RESULT: We identified 15 differentially expressed genes associated with aging (ARDEGs). The SVM-RFE and LASSO algorithms pinpointed four potential diagnostic biomarkers. Analysis of external datasets confirmed significant differences in PIK3R1 expression. RT-qPCR results indicated decreased expression of hub genes. The ROC curve demonstrated that PIK3R1 exhibited strong diagnostic capability for COPD. CONCLUSION: We identified 15 differentially expressed genes associated with aging. Among them, PIK3R1 showed differences in external data sets and RT-qPCR results. Therefore, PIK3R1 may play an essential role in regulating aging involved in COPD.

Compound-protein interaction prediction based on heterogeneous network reveals potential antihepatoma agents.

Despite the development of an increasing number of multi-kinase and immune checkpoint inhibitors for hepatocellular carcinoma (HCC), improvement in cancer survival remains limited due to their similar structures and targets. Natural products (NPs) maintain diverse structures and activities and are important sources of drug discovery. Currently, most of active NPs exhibit ambiguous binding targets and mechanisms. Herein, we proposed the CIPHEN (compound-protein interactions prediction based on the heterogeneous network) to predict potential antihepatoma NPs and their targets. The evaluation of canonical compound-protein interactions (CPIs) databases and independent test demonstrated the good ability of CPIHN to reveal known and unreported CPIs. Both prediction and experiment results indicated that CIPHEN could unveil relationships between actively antihepatoma sesquiterpenoid dimers (SDs) and anti-HCC targets. In conclusion, the CIPHEN provides a promising choice to investigate the mode of action of compounds, which will help to accelerate the process of drug research and development against HCC.

The effect of salinity on trimethoprim adsorption by activated sludge extracellular polymeric substances at trace concentration.

The saline wastewater produced in industrial activities and seawater use would flow into wastewater treatment plants and affect the characteristic of extracellular polymeric substance (EPS) of activated sludge, which could potentially impact the removal of antibiotics via adsorption. Nonetheless, the effect of salinity on trimethoprim adsorption by activated sludge extracellular polymeric substances at trace concentration and the underlying mechanism remain largely unknown. In this study, the effect of salinity on the adsorption removal of a typical antibiotic, i.e., trimethoprim (TMP) at trace concentration (25.0 µg/L) was evaluated. The results showed the content of EPS was decreased significantly from 56.36 to 21.70 mg/g VSS when the salinity was increased from 0 to 10 g/L. Protein fractions occupied the predominant component of EPS, whose concentration was decreased from 38.17 to 12.83 mg/g VSS. The equilibrium adsorption capacity of activated sludge for TMP was decreased by 49.70% (from 4.97 to 2.50 µg/g VSS). The fluorescence quenching results indicated the fluorescence intensity of tryptophan-like substances was decreased by 30% and the adsorption sites of EPS were decreased from 0.51 to 0.21 when the salinity was increased. The infrared spectrum and XPS results showed that the nitrogen-containing groups from protein were decreased significantly. The circular dichroic analysis showed α helix structure of protein in EPS was decreased with the increase of salinity, which was responsible for the decrease of adsorption capacity for TMP.

Saikosaponin A attenuates osteoclastogenesis and bone loss by inducing ferroptosis.

To alleviate bone loss, most current drugs target osteoclasts. Saikosaponin A (Ssa), a triterpene saponin derived from Bupleurum falcatum (also known as Radix bupleuri), has immunoregulatory, neuromodulatory, antiviral, anticancer, anti-convulsant, anti-inflammatory, and anti-proliferative effects. Recently, modulation of bone homeostasis was shown to involve ferroptosis. Herein, we aimed to determine Ssa's inhibitory effects on osteoclastogenesis and differentiation, whether ferroptosis is involved, and the underlying mechanisms. Tartrate-resistant acid phosphatase (TRAP) staining, F-actin staining, and pit formation assays were conducted to confirm Ssa-mediated inhibition of RANKL-induced osteoclastogenesis in vitro. Ssa could promote osteoclast ferroptosis and increase mitochondrial damage by promoting lipid peroxidation, as measured by iron quantification, FerroOrange staining, Dichloro-dihydro-fluorescein diacetate, MitoSOX, malondialdehyde, glutathione, and boron-dipyrromethene 581/591 C11 assays. Pathway analysis showed that Ssa can promote osteoclasts ferroptosis by inhibiting the Nrf2/SCL7A11/GPX4 axis. Notably, we found that the ferroptosis inhibitor ferrostatin-1 and the Nrf2 activator tert-Butylhydroquinone reversed the inhibitory effects of Ssa on RANKL-induced osteoclastogenesis. In vivo, micro-computed tomography, hematoxylin and eosin staining, TRAP staining, enzyme-linked immunosorbent assays, and immunofluorescence confirmed that in rats with periodontitis induced by lipopolysaccharide, treatment with Ssa reduced alveolar bone resorption dose-dependently. The results suggested Ssa as a promising drug to treat osteolytic diseases.