Apigenin suppresses epithelial-mesenchymal transition in high glucose-induced retinal pigment epithelial cell by inhibiting CBP/p300-mediated histone acetylation.

Epithelial mesenchymal transition (EMT) is a critical process implicated in the pathogenesis of retinal fibrosis and the exacerbation of diabetic retinopathy (DR) within retinal pigment epithelium (RPE) cells. Apigenin (AP), a potential dietary supplement for managing diabetes and its associated complications, has demonstrated inhibitory effects on EMT in various diseases. However, the specific impact and underlying mechanisms of AP on EMT in RPE cells remain poorly understood. In this study, we have successfully validated the inhibitory effects of AP on high glucose-induced EMT in ARPE-19 cells and diabetic db/db mice. Notably, our findings have identified CBP/p300 as a potential therapeutic target for EMT in RPE cells and have further substantiated that AP effectively downregulates the expression of EMT-related genes by attenuating the activity of CBP/p300, consequently reducing histone acetylation alterations within the promoter region of these genes. Taken together, our results provide novel evidence supporting the inhibitory effect of AP on EMT in RPE cells, and highlight the potential of specifically targeting CBP/p300 as a strategy for inhibiting retinal fibrosis in the context of DR.

The Evolution, Expression Patterns, and Domestication Selection Analysis of the Annexin Gene Family in the Barley Pan-Genome.

Plant annexins constitute a conserved protein family that plays crucial roles in regulating plant growth and development, as well as in responses to both biotic and abiotic stresses. In this study, a total of 144 annexin genes were identified in the barley pan-genome, comprising 12 reference genomes, including cultivated barley, landraces, and wild barley. Their chromosomal locations, physical-chemical characteristics, gene structures, conserved domains, and subcellular localizations were systematically analyzed to reveal the certain differences between wild and cultivated populations. Through a cis-acting element analysis, co-expression network, and large-scale transcriptome analysis, their involvement in growth, development, and responses to various stressors was highlighted. It is worth noting that HvMOREXann5 is only expressed in pistils and anthers, indicating its crucial role in reproductive development. Based on the resequencing data from 282 barley accessions worldwide, genetic variations in thefamily were investigated, and the results showed that 5 out of the 12 identified HvMOREXanns were affected by selection pressure. Genetic diversity and haplotype frequency showed notable reductions between wild and domesticated barley, suggesting that a genetic bottleneck occurred on the annexin family during the barley domestication process. Finally, qRT-PCR analysis confirmed the up-regulation of HvMOREXann7 under drought stress, along with significant differences between wild accessions and varieties. This study provides some insights into the genome organization and genetic characteristics of the annexin gene family in barley at the pan-genome level, which will contribute to better understanding its evolution and function in barley and other crops.

Identification of ALDOB as a novel prognostic biomarker in kidney clear cell renal cell carcinoma.

Kidney clear cell renal cell carcinoma (KIRC) is also the most lethal subtype among all kidney cancer subtypes, posing a severe threat to public health. Therefore, it is crucial to identify new, reliable biomarkers in KIRC. Therefore, it is crucial to identify novel, reliable biomarkers associated with KIRC. We analyzed RNA sequence results from TCGA and several GEO datasets. The commonly deregulated gene, ALDOB, was found in multiple data and confirmed its important prognostic value. Subsequently, we explored the specific mechanism by which ALDOB regulates anti-tumor immunity through in vivo and in vitro experiments. We found that ALDOB may play a role in regulating tumor growth by regulating CD8+ T cell infiltration. This is consistent with the results of our immune infiltration-related analysis. In addition, we have also discovered the effect of ALDOB in previous studies on other cancer types. Finally, we concluded that ALDOB may have potential reference value for immunotherapy and can also be used as an independent predictor of prognosis in KIRC.

Nonconventional Electrochemical Reactions in Rechargeable Lithium-Sulfur Batteries.

Rechargeable lithium-sulfur (Li-S) batteries are promising for high-energy storage. However, conventional redox reactions involving sulfur (S) and lithium (Li) can lead to unstable intermediates. Over the past decade, many strategies have emerged to address this challenge, enabling nonconventional electrochemical reactions in Li-S batteries. In our Perspective, we provide a brief review of these strategies and highlight their potential benefits. Specifically, our group has pioneered a top-down approach, investigating Li-S reactions at molecular and subatomic levels, as demonstrated in our recent work on stable S isotopes. These insights not only enhance understanding of charge transfer and storage properties but also offer exciting opportunities for advancements in battery materials research.

Loureirin B ameliorates cholestatic liver fibrosis via AKT/mTOR/ATG7-mediated autophagy of hepatic stellate cells.

AIM OF THE STUDY: Chronic cholestasis leads to liver fibrosis, which lacks effective treatment. In this study, we investigated the role and mechanisms of action of loureirin B (LB) in cholestatic liver fibrosis. MATERIALS AND METHODS: Bile duct ligation (BDL)-induced hepatic fibrosis mice were used as in vivo models. Transforming growth factor-ß1 (TGF-ß1)-pretreated HSC-T6 cells were used to explore the mechanism by which LB attenuates liver fibrosis in vitro. RNA sequencing, quantitative PCR (qPCR), western blotting, immunohistochemistry and immunofluorescence were performed to detect the fibrosis markers and measure autophagy levels. Flow cytometry, cell counting kit-8 (CCK-8) assay, and 5'-ethynyl-2'-deoxyuridine (EdU) assay were conducted to detect cell proliferation and viability. GFP-RFP-LC3 adenovirus, autophagy-related protein 7 (ATG7) siRNA, and bafilomycin A1 (BafA1) were used to verify autophagic flux. RESULTS: Our results showed that LB ameliorates liver injury, inhibits collagen deposition, and decreases the expressions of fibrosis-related markers in BDL-induced mouse livers. In vitro, we found that LB inhibited proliferation and migration, promoted apoptosis, and inhibited the activation of HSC-T6 cells pretreated with TGF-ß1. RNA sequencing analysis of HSC-T6 cells showed that LB treatment predominantly targeted autophagy-related pathways. Further protein analysis indicated that LB downregulated the expression of phosphorylated AKT (p-AKT) and phosphorylated mTOR (p-mTOR), and upregulated LC3-II, p62, and ATG7 both in vivo and in vitro. Intriguingly, ATG7 inactivation reversed the antifibrotic effects of LB on HSC-T6 cells. CONCLUSIONS: LB can improve BDL-induced liver fibrosis by inhibiting the activation and proliferation of HSCs and is expected to be a promising antifibrotic drug.

Emergence of eravacycline heteroresistance in carbapenem-resistant Acinetobacter baumannii isolates in China.

Carbapenem-resistant Acinetobacter baumannii (CRAB) is resistant to almost all antibiotics. Eravacycline, a newer treatment option, has the potential to treat CRAB infections, however, the mechanism by which CRAB isolates develop resistance to eravacycline has yet to be clarified. This study sought to investigate the features and mechanisms of eravacycline heteroresistance among CRAB clinical isolates. A total of 287 isolates were collected in China from 2020 to 2022. The minimum inhibitory concentration (MIC) of eravacycline and other clinically available agents against A. baumannii were determined using broth microdilution. The frequency of eravacycline heteroresistance was determined by population analysis profiling (PAP). Mutations and expression levels of resistance genes in heteroresistant isolates were determined by polymerase chain reaction (PCR) and quantitative real-time PCR (qRT-PCR), respectively. Antisense RNA silencing was used to validate the function of eravacycline heteroresistant candidate genes. Twenty-five eravacycline heteroresistant isolates (17.36%) were detected among 144 CRAB isolates with eravacycline MIC values ≤4 mg/L while no eravacycline heteroresistant strains were detected in carbapenem-susceptible A. baumannii (CSAB) isolates. All eravacycline heteroresistant strains contained OXA-23 carbapenemase and the predominant multilocus sequence typing (MLST) was ST208 (72%). Cross-resistance was observed between eravacycline, tigecycline, and levofloxacin in the resistant subpopulations. The addition of efflux pump inhibitors significantly reduced the eravacycline MIC in resistant subpopulations and weakened the formation of eravacycline heteroresistance in CRAB isolates. The expression levels of adeABC and adeRS were significantly higher in resistant subpopulations than in eravacycline heteroresistant parental strains (P < 0.05). An ISAba1 insertion in the adeS gene was identified in 40% (10/25) of the resistant subpopulations. Decreasing the expression of adeABC or adeRS by antisense RNA silencing significantly inhibited eravacycline heteroresistance. In conclusion, this study identified the emergence of eravacycline heteroresistance in CRAB isolates in China, which is associated with high expression of AdeABC and AdeRS.

Climate change influences on the streamflow and sediment supply to the Chao Phraya River basin, Thailand.

This study investigates the effects of climate change on the sediment loads of the Ping and Wang River basins and their contribution to the sediment dynamics of the lower Chao Phraya River basin in Thailand. The various climate models under different Representative Concentration Pathways (RCPs) scenarios are employed to project sediment loads in future. The findings indicate a significant increase in river flow approximately 20% in the Ping River (PR) and 35% in the Wang River (WR) by the mid-21st century and continuing into the distant future. Consequently, this is expected to result in sediment loads up to 0.33 × 106 t/y in the PR and 0.28 × 106 t/y in the WR. This escalation is particularly notable under the RCP 8.5 scenario, which assumes higher greenhouse gas emissions. Additionally, the research provides insights into the potential positive implications for the Chao Phraya Delta's coastal management. Without further damming in the Ping and Wang River basins, the anticipated rise in sediment supply could aid in mitigating the adverse effects of land subsidence and sea-level rise, which have historically caused extensive shoreline retreat in the delta region, particularly around Bangkok Metropolis. The paper concludes that proactive adaptation strategies are required to manage the expected changes in the hydrological and sediment regimes to protect vulnerable coastal zones and ensure the sustainable management of the Chao Phraya River Basin in the face of climate change.

Paeoniflorin promotes PPARγ expression to suppress HSCs activation by inhibiting EZH2-mediated histone H3K27 trimethylation.

BACKGROUND: The alleviating effect of paeoniflorin (Pae) on liver fibrosis has been established; however, the molecular mechanism and specific target(s) underlying this effect remain elusive. PURPOSE: This study was to investigate the molecular mechanism underlying the regulatory effect of Pae on hepatic stellate cells (HSCs) activation in liver fibrosis, with a specific focus on the role of Pae in modulating histone methylation modifications. METHODS: The therapeutic effect of Pae was evaluated by establishing in vivo and in vitro models of carbon tetrachloride (CCl4)-induced mice and transforming growth factor ß1 (TGF-ß1)-induced LX-2 cells, respectively. Molecular docking, surface plasmon resonance (SPR), chromatin immunoprecipitation-quantitative real time PCR (ChIP-qPCR) and other molecular biological methods were used to clarify the molecular mechanism of Pae regulating HSCs activation. RESULTS: Our study found that Pae inhibited HSCs activation and histone trimethylation modification in liver of CCl4-induced mice and LX-2 cells. We demonstrated that the inhibitory effect of Pae on the activation of HSCs was dependent on peroxisome proliferator-activated receptor γ (PPARγ) expression and enhancer of zeste homolog 2 (EZH2). Mechanistically, Pae directly binded to EZH2 to effectively suppress its enzymatic activity. This attenuation leaded to the suppression of histone H3K27 trimethylation in the PPARγ promoter region, which induced upregulation of PPARγ expression. CONCLUSION: This investigative not only sheds new light on the precise targets that underlie the remission of hepatic fibrogenesis induced by Pae but also emphasizes the critical significance of EZH2-mediated H3K27 trimethylation in driving the pathogenesis of liver fibrosis.

FIB-4 index is associated with mortality in critically ill patients with alcohol use disorder: Analysis from the MIMIC-IV database.

BACKGROUND: The relationship between fibrosis-4 (FIB-4) index and all-cause mortality in critically ill patients with alcohol use disorder (AUD) is unclear. The present study aimed to investigate the predictive ability of FIB-4 for all-cause mortality in critically ill AUD patients and the association between them. METHODS: A total of 2528 AUD patients were included using the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. FIB-4 was calculated for each patient using the existing formula. The patients were equally divided into four groups based on the quartiles of FIB-4. Multivariate logistic regression and Cox proportional hazard model were used to evaluate the association of FIB-4 with in-hospital mortality, 28-day mortality and 1-year mortality. Kaplan-Meier curves were used to analyse the incidence of 28-day mortality among four groups. RESULTS: FIB-4 was positively associated with 28-day mortality of AUD patients with hazard ratio (HR) of 1.354 [95% confidence interval (CI) 1.192-1.538]. There were similar trends in the in-hospital mortality [odds ratio (OR): 1.440, 95% CI (1.239-1.674)] and 1-year mortality [HR: 1.325, 95% CI (1.178-1.490)]. CONCLUSION: Increased FIB-4 is associated with greater in-hospital mortality, 28-day mortality and 1-year mortality in critically ill AUD patients.

Songorine modulates macrophage polarization and metabolic reprogramming to alleviate inflammation in osteoarthritis.

Introduction: Osteoarthritis (OA) is a prevalent joint disorder characterized by multifaceted pathogenesis, with macrophage dysregulation playing a critical role in perpetuating inflammation and joint degeneration. Methods: This study focuses on Songorine, derived from Aconitum soongaricum Stapf, aiming to unravel its therapeutic mechanisms in OA. Comprehensive analyses, including PCR, Western blot, and immunofluorescence, were employed to evaluate Songorine's impact on the joint microenvironment and macrophage polarization. RNA-seq analysis was conducted to unravel its anti-inflammatory mechanisms in macrophages. Metabolic alterations were explored through extracellular acidification rate monitoring, molecular docking simulations, and PCR assays. Oxygen consumption rate measurements were used to assess mitochondrial oxidative phosphorylation, and Songorine's influence on macrophage oxidative stress was evaluated through gene expression and ROS assays. Results: Songorine effectively shifted macrophage polarization from a pro-inflammatory M1 phenotype to an anti-inflammatory M2 phenotype. Notably, Songorine induced metabolic reprogramming, inhibiting glycolysis and promoting mitochondrial oxidative phosphorylation. This metabolic shift correlated with a reduction in macrophage oxidative stress, highlighting Songorine's potential as an oxidative stress inhibitor. Discussion: In an in vivo rat model of OA, Songorine exhibited protective effects against cartilage damage and synovial inflammation, emphasizing its therapeutic potential. This comprehensive study elucidates Songorine's multifaceted impact on macrophage modulation, metabolic reprogramming, and the inflammatory microenvironment, providing a theoretical foundation for its therapeutic potential in OA.

The social network perspective on power system co-evolution: responses to "double carbon target" realization in China.

The introduction of dual carbon targets will significantly impact power system development. Despite this, there is currently limited research on achieving system evolution and transition while ensuring safety, low-carbon output, and efficiency, as well as quantitatively analyzing the resulting changes dual carbon targets will have on the power system. Co-evolution of the power system offers a solution to balance the impact of dual carbon goals and enhance interaction among system entities, thereby facilitating the achievement of these goals. Our study focuses on constructing an evolutionary topological network by analyzing the dynamic evolution rule of power systems. We investigate the co-evolution pattern of power systems by analyzing the relationship between the role of power system agents and their dynamic structures. Furthermore, we analyze the future structural changes of power systems, which can provide theoretical support for achieving dual carbon goals in the power system. Our findings highlight key measures to promote synergistic evolution, including increasing energy storage capabilities, stabilizing renewable energy supply, breaking inter-provincial barriers in electricity transmission, and developing a multi-level intelligent power system. Through link analysis, we discover that future power systems will maintain a mild coordination among agents rather than implementing large-scale realignment and reconfiguration. We posit that overcoming obstacles can be achieved by fostering cohesion between the network and agents through technological innovation and widespread market diffusion to drive co-evolution.

Motor symptoms of Parkinson's disease are affected by temperature: A controlled pilot study.

PURPOSE: The motor symptoms (MS) of Parkinson's disease (PD) have been affecting the quality of life in patients. In clinical practice, most patients with PD report that MS are more severe in winter than in summer, and hyperthermic baths (HTB) could temporarily improve MS. The study aimed to evaluate the effects of seasonal variation and aquatic thermal environment of HTB on the MS of PD. PATIENTS AND METHODS: A cross-sectional study of 203 Chinese Han patients was performed. Univariate and multivariate analyses were performed to analyze seasonal variation in MS relative to baseline data (sex, age at onset, duration, season of birth, Hoehn and Yahr stage, family history, levodopa equivalent dose, and the effect of HTB on MS). Ten subjects participated in the HTB study, and one patient dropped out. The paired Wilcoxon rank test was used to assess the differences in the Movement Disorder Society-United Parkinson's disease Rating Scale (MDS-UPDRS) part III motor examination total scores and the modified Webster Symptoms Score between non-HTB and before HTB and between non-HTB and after HTB. RESULTS: The improvement of MS after HTB was an independent risk factor for seasonal variation in MS (OR, 25.203; 95% CI, 10.951-58.006; p = .000). Patients with PD had significant improvements in the MDS-UPDRS part III motor examination total scores, especially in bradykinesia (p = .043), rigidity (p = .008), posture (p = .038), and rest tremor amplitude (p = .047). CONCLUSION: Seasonal variation in temperature and water temperature of HTB may affect MS in some patients with PD. Simple HTB could be recommended as physiotherapy for patients with PD who report temperature-sensitive MS.

Case report: A lung squamous cell carcinoma patient with a rare EGFR G719X mutation and high PD-L1 expression showed a good response to anti-PD1 therapy.

Lung cancer treatment has transitioned fully into the era of immunotherapy, yielding substantial improvements in survival rate for patients with advanced non-small cell lung cancer (NSCLC). In this report, we present a case featuring a rare epidermal growth factor receptor (EGFR) mutation accompanied by high programmed death-ligand 1 (PD-L1) expression, demonstrating remarkable therapeutic efficacy through a combination of immunotherapy and chemotherapy. A 77-year-old male with no family history of cancer suffered from upper abdominal pain for more than half months in August 2020 and was diagnosed with stage IV (cT3N3M1c) lung squamous cell carcinoma (LUSC) harboring both a rare EGFR p.G719C mutation and high expression of PD-L1 (tumor proportion score [TPS] = 90%). Treatment with the second-generation targeted therapy drug Afatinib was initiated on September 25, 2020. However, resistance ensued after 1.5 months of treatment. On November 17, 2020, immunotherapy was combined with chemotherapy (Sintilimab + Albumin-bound paclitaxel + Cisplatin), and a CT scan conducted three months later revealed significant tumor regression with a favorable therapeutic effect. Subsequently, the patient received one year of maintenance therapy with Sintilimab, with follow-up CT scans demonstrating subtle tumor shrinkage (stable disease). This case provides evidence for the feasibility and efficacy of immunotherapy combined with chemotherapy in the treatment of EGFR-mutated and PD-L1 highly expressed LUSC.

High-Temperature Phase Transition with Switchable Dielectric Behavior and Significant Photoluminescence Changes in a Zero-Dimensional Hybrid SbBr6 Perovskite.

In the past decade, metal halide materials have been favored by many researchers because of their excellent physical and chemical properties under thermal, electrical, and light stimuli, such as ferroelectricity, dielectric, nonlinearity, fluorescence, and semiconductors, greatly promoting their application in optoelectronic devices. In this study, we successfully constructed an unleaded organic-inorganic hybrid perovskite crystal: [Cl-C6H4-(CH2)2NH3]3SbBr6 (1), which underwent a high-temperature reversible phase transition near Tp = 368 K. The phase transition behavior of 1 was characterized by differential scanning calorimetry, accompanied by a thermal hysteresis of 6 K. In addition, variable-temperature Raman spectroscopy analysis and PXRD further verified the sensitivity of 1 to temperature and the phase transition from low symmetry to high symmetry. Temperature-dependent dielectric testing shows that 1 can be a sensitive switching dielectric constant switching material. Remarkably, 1 exhibits strong photoluminescence emission with a wavelength of 478 nm and a narrow band gap of 2.7 eV in semiconductors. As the temperature increases and decreases, fluorescence undergoes significant changes, especially near Tc, which further confirms the reversible phase transition of 1. All of these findings provide new avenues for designing and assembling new phase change materials with high Tp and photoluminescence properties.

Morphine- and foot shock-responsive neuronal ensembles in the VTA possess different connectivity and biased GPCR signaling pathway.

Background: Neurons in the ventral tegmental area (VTA) are sensitive to stress and their maladaptation have been implicated in the psychiatric disorders such as anxiety and addiction, etc. The cellular properties of the VTA neurons in response to different stressors related to different emotional processing remain to be investigated. Methods: By combining immediate early gene (IEG)-dependent labeling, rabies virus tracing, ensemble-specific transcriptomic analysis and fiber photometry recording in the VTA of male mice, the spatial distribution, brain-wide connectivity and cellular signaling pathways in the VTA neuronal ensembles in response to morphine (Mor-Ens) or foot shock (Shock-Ens) stimuli were investigated. Results: Optogenetic activation of the Mor-Ens drove approach behavior, whereas chemogenetic activation of the Shock-Ens increased the anxiety level in mice. Mor-Ens were clustered and enriched in the ventral VTA, contained a higher proportion of dopaminergic neurons, received more inputs from the dorsal medial striatum and the medial hypothalamic zone, and exhibited greater axonal arborization in the zona incerta and ventral pallidum. Whereas Shock-Ens were more dispersed, contained a higher proportion of GABAergic neurons, and received more inputs from the ventral pallidum and the lateral hypothalamic area. The downstream targets of the G protein and ß-arrestin pathways, PLCß3 and phosphorylated AKT1Thr308, were relatively enriched in the Mor-Ens and Shock-Ens, respectively. Cariprazine, the G-protein-biased agonist for the dopamine D2 receptor, increased the response of Mor-Ens to sucrose water and decreased the anxiety-like behavior during morphine withdrawal, whereas the ß-arrestin-biased agonist UNC9994 decreased the response of Shock-Ens to tail suspension. Conclusions: Taken together, these findings reveal the heterogeneous connectivity and signaling pathways of the VTA neurons in response to morphine and foot shock, providing new insights for development of specific interventions for psychiatric disorders caused by various stressors associated with different VTA neuronal functions.

Projections from infralimbic medial prefrontal cortex glutamatergic outputs to amygdala mediates opioid induced hyperalgesia in male rats.

Repeated use of opioid analgesics may cause a paradoxically exacerbated pain known as opioid-induced hyperalgesia (OIH), which hinders effective clinical intervention for severe pain. Currently, little is known about the neural circuits underlying OIH modulation. Previous studies suggest that laterocapsular division of the central nucleus of amygdala (CeLC) is critically involved in the regulation of OIH. Our purpose is to clarify the role of the projections from infralimbic medial prefrontal cortex (IL) to CeLC in OIH. We first produced an OIH model by repeated fentanyl subcutaneous injection in male rats. Immunofluorescence staining revealed that c-Fos-positive neurons were significantly increased in the right CeLC in OIH rats than the saline controls. Then, we used calcium/calmodulin-dependent protein kinase IIα (CaMKIIα) labeling and the patch-clamp recordings with ex vivo optogenetics to detect the functional projections from glutamate pyramidal neurons in IL to the CeLC. The synaptic transmission from IL to CeLC, shown in the excitatory postsynaptic currents (eEPSCs), inhibitory postsynaptic currents (eIPSCs) and paired-pulse ratio (PPR), was observably enhanced after fentanyl administration. Moreover, optogenetic activation of this IL-CeLC pathway decreased c-Fos expression in CeLC and ameliorated mechanical and thermal pain in OIH. On the contrary, silencing this pathway by chemogenetics exacerbated OIH by activating the CeLC. Combined with the electrophysiology results, the enhanced synaptic transmission from IL to CeLC might be a cortical gain of IL to relieve OIH rather than a reason for OIH generation. Scaling up IL outputs to CeLC may be an effective neuromodulation strategy to treat OIH.

Intraoperative electroencephalogram features related to frailty in older patients: an exploratory prospective observational study.

Frailty is an independent risk factor for the increased incidence of postoperative delirium (POD). To date, the effect of frailty on intraoperative electroencephalogram (EEG) changes remains unexplored. The present study, an exploratory analysis of a prospective cohort study, aimed to investigate the differences in EEG characteristics between frail and robust patients. This prospective observational study was conducted between December 2020 and November 2021. The preoperative frailty status was assessed using the FRAIL scale. The patients' baseline (before anesthesia) and intraoperative EEG data were collected using a brain function monitor. Finally, 20 robust and 26 frail older patients scheduled for elective spinal surgery or transurethral prostatectomy under propofol-based general anesthesia were included in the final analysis. Baseline and intraoperative EEG spectrogram and power spectra were compared between the frail and robust groups. No differences were observed in baseline EEG between the frail and robust groups. When the intraoperative EEG spectral parameters were compared, the alpha peak frequency (10.56 ± 0.49 vs. 10.14 ± 0.36 Hz, P = 0.002) and alpha peak, delta, theta, alpha, and beta powers were lower in the frail group. After adjusting for age, Charlson Comorbidity Index (CCI), and mini-mental state examination (MMSE) score, the FRAIL score was still negatively associated with total, delta, theta, alpha, and beta powers. Frail patients had reduced EEG (0-30 Hz) power after the induction of propofol-based general anesthesia. After adjusting for age, CCI, and MMSE score, frail patients still showed evidence of reduced δ, θ, α, and ß power.

Novel Insights into Prokineticin 1 Role in Pregnancy-related Diseases.

Prokineticin 1 (PROK1) is a secreted protein involved in a range of physiological activities such as cell proliferation, migration, angiogenesis, and neuronal cell proliferation. Emerging evidences show that PROK1/PROK receptors (PROKRs) are expressed by trophoblasts, and decidual stroma cells at the maternal-fetal interface. PROK1 plays a critical role in successful pregnancy establishment by regulating the decidualization, implantation and placental development. Dysregulation of prokineticin signaling has been described in certain pathological states associated with pregnancy, including pre-eclampsia, recurrent miscarriage and fetal growth restriction. In this review, the expression and pleiotropic roles of PROK1 under physiological and pathological pregnancy conditions are discussed.

Network Pharmacology and Experimental Validation Explore the Pharmacological Mechanisms of Herb Pair for Treating Rheumatoid Arthritis.

OBJECTIVE: This study aimed to elucidate the multitarget mechanism of the Mori Ramulus - Taxilli Herba (MT) herb pair in treating rheumatoid arthritis (RA). METHODS: The targets of the herb pair and RA were predicted from databases and screened through cross-analysis. The core targets were obtained using protein-protein interaction (PPI) network analysis. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed. Finally, animal experiments were conducted to validate the anti-RA effect and mechanism of this herb pair. RESULTS: This approach successfully identified 9 active compounds of MT that interacted with 6 core targets (AKT1, TNF, IL6, TP53, VEGFA, and IL1ß). Pathway and functional enrichment analyses revealed that MT had significant effects on the TNF and IL-17 signaling pathways. The consistency of interactions between active components and targets in these pathways was confirmed through molecular docking. Moreover, the potential therapeutic effect of MT was verified in vivo, demonstrating its ability to effectively relieve inflammation by regulating these targeted genes and pathways. CONCLUSION: The present work suggests that the therapeutic effect of MT herb pair on RA may be attributed to its ability to regulate the TNF signaling pathway and IL-17 signaling pathway.

Outcome of chairside CAD/CAM ceramic restorations on endodontically treated posterior teeth: a prospective study.

OBJECTIVE: The aim of this study was to evaluate the outcome and risk factors for chairside CAD/CAM full cusp coverage restorations on endodontically treated posterior teeth after 3 years of follow-up. METHODS: A total of 245 endodontically treated posterior teeth of 224 patients were included and restored with CAD/CAM full cusp coverage all-ceramic restorations according to a standardized protocol. Patients were recalled after treatments 1 to 3 years and underwent clinical and radiological examinations. At recall, modified FDI criteria were used to determine treatment outcomes by 2 evaluators. Success was determined when FDI scores were 1-2, and failure was indicated when FDI scores were 5. Logistic regression analysis was performed to evaluate potential risk factors. RESULTS: A total of 183 patients presented at recall, and the clinical outcomes of 201 teeth were analyzed with a recall rate of 82.0% for teeth and 81.7% for patients after 1-3 years of follow-up.185 of 201 teeth were found to have FDI scores of 1-2, and the success rate was 92%. No teeth were extracted during the follow-up period. Fourteen failed cases with an FDI score of 5 presented restoration dislocation, fracture of restoration or/and tooth. Logistic regression analysis revealed that oral parafunction (OR 2.281, 95% CI 2.2 ~ 47.5, P value 0.01) was a risk factor for success rate. CONCLUSION: Chairside CAD/CAM all-ceramic full cusp coverage restoration was (could be) a promising alternative for restoring endodontically treated posterior teeth.