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1.
iScience ; 27(6): 109924, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38827403

ABSTRACT

Since the Russia-Ukraine war in February 2022, European electricity prices have experienced considerable turbulence, primarily attributed to a shortage in the natural gas supply. We investigate the relationship between natural gas prices in the European continent and electricity prices in Nordic countries before and after the outbreak of war. Despite the low proportion of natural gas electricity generation, the empirical analysis reveals both direct and indirect transmission paths for natural gas prices in Nordic countries. Meanwhile, the theoretical analysis demonstrates how Nordic renewable (wind and solar) and other non-gas generators exercise market power through price bidding in the anticipation of an increase in gas prices or a shortage of gas supply, which results in higher electricity prices. Understanding the underlying factors and dynamics driving substantial price fluctuations in the Nordic electricity market is essential for comprehending the intricate interconnections within the European energy landscape.

2.
Org Lett ; 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38836549

ABSTRACT

A highly ortho-selective CAr-H olefination of tertiary anilines without a directing group was developed. This reaction tolerated various substituted arenes and olefin coupling partners, affording ortho-olefination products in moderate to good yields. Preliminary mechanistic studies showed that N-Ac-d-Ala, Ag2CO3, and BQ were the key factors for tuning the regioselectivity from para to ortho. Density functional theory was used to achieve a theoretical understanding of the ortho selectivity.

3.
J Am Chem Soc ; 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38837941

ABSTRACT

The absolute band edge positions and work function (Φ) are the key electronic properties of metal oxides that determine their performance in electronic devices and photocatalysis. However, experimental measurements of these properties often show notable variations, and the mechanisms underlying these discrepancies remain inadequately understood. In this work, we focus on ceria (CeO2), a material renowned for its outstanding oxygen storage capacity, and combine theoretical and experimental techniques to demonstrate environmental modifications of its ionization potential (IP) and Φ. Under O-deficient conditions, reduced ceria exhibits a decreased IP and Φ with significant sensitivity to defect distributions. In contrast, the IP and Φ are elevated in O-rich conditions due to the formation of surface peroxide species. Surface adsorbates and impurities can further augment these variabilities under realistic conditions. We rationalize the shifts in energy levels by separating the individual contributions from bulk and surface factors, using hybrid quantum mechanical/molecular mechanical (QM/MM) embedded-cluster and periodic density functional theory (DFT) calculations supported by interatomic-potential-based electrostatic analyses. Our results highlight the critical role of on-site electrostatic potentials in determining the absolute energy levels in metal oxides, implying a dynamic evolution of band edges under catalytic conditions.

4.
J Adv Res ; 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38844123

ABSTRACT

INTRODUCTION: Osteoarthritis (OA) is the most common arthritis that is characterized by the progressive synovial inflammation and loss of articular cartilage. Although GYY4137 is a novel and slow-releasing hydrogen sulfide (H2S) donor with potent anti-inflammatory properties that may modulate the progression of OA, its underlying mechanism remains unclear. OBJECTIVES: In this study, we validated the protective role of GYY4137 against OA pathological courses and elucidated its underlying regulatory mechanisms. METHODS: Cell transfection, immunofluorescence staining, EdU assay, transmission electron microscopy, mitochondrial membrane potential measurement, electrophoretic mobility shift assay, sulfhydration assay, qPCR and western blot assays were performed in the primary mouse chondrocytes or the mouse macrophage cell line raw 264.7 for in vitro study. DMM-induced OA mice model and Macrophage-specific p65 knockout (p65f/f LysM-CreERT2) mice on the C57BL/6 background were used for in vivo study. RESULTS: We found that GYY4137 can alleviate OA progress by suppressing synovium pyroptosis in vivo. Moreover, our in vitro data revealed that GYY4137 attenuates inflammation-induced NLRP3 and caspase-1 activation and results in a decrease of IL-1ß production in macrophages. Mechanistically, GYY4137 increased persulfidation of NF-kB p65 in response to inflammatory stimuli that results in a decrease of cellular reactive oxygen species (ROS) accumulation and ameliorates mitochondrial dysfunctions. Using site-directed mutagenesis, we showed that H2S persulfidates cysteine38 in p65 protein and hampers p65 transcriptional activity, and p65 mutant impaired macrophage responses to GYY4137. CONCLUSION: These findings suggest a mechanism by which GYY4137 through redox modification of p65 participates in inhibiting NLRP3 activation by OA to regulate inflammatory responses. Thus, we propose that GYY4137 represents a promising novel therapeutic strategy for the treatment of OA.

5.
Chem Sci ; 15(20): 7714-7724, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38784755

ABSTRACT

Photo-thermal-synergistic hydrogenation is a promising strategy for upcycling carbon dioxide into fuels and chemicals by maximally utilizing full-spectrum solar energy. Herein, by immobilizing Pt-Rh bimetal onto a well-developed GaN NWs/Si platform, CO2 was photo-thermo-catalytically hydrogenated towards CO under concentrated light illumination without extra energies. The as-designed architecture demonstrates a considerable CO evolution rate of 11.7 mol gGaN-1 h-1 with a high selectivity of 98.5% under concentrated light illumination of 5.3 W cm-2, leading to a benchmark turnover frequency of 26 486 mol CO per mol PtRh per hour. It is nearly 2-3 orders of magnitude higher than that of pure thermal catalysis under the same temperature by external heating without light. Control experiments, various spectroscopic characterization methods, and density functional theory calculations are correlatively conducted to reveal the origin of the remarkable performance as well as the photo-thermal enhanced mechanism. It is found that the recombination of photogenerated electron-hole pairs is dramatically inhibited under high temperatures arising from the photothermal effect. More critically, the synergy between photogenerated carriers arising from ultraviolet light and photoinduced heat arising from visible- and infrared light enables a sharp reduction of the apparent activation barrier of CO2 hydrogenation from 2.09 downward to 1.18 eV. The evolution pathway of CO2 hydrogenation towards CO is also disclosed at the molecular level. Furthermore, compared to monometallic Pt, the introduction of Rh further reduces the desorption energy barrier of *CO by optimizing the electronic properties of Pt, thus enabling the achievement of excellent activity and selectivity. This work provides new insights into CO2 hydrogenation by maximally utilizing full-spectrum sunlight via photo-thermal synergy.

6.
Brain Behav ; 14(5): e3512, 2024 May.
Article in English | MEDLINE | ID: mdl-38747874

ABSTRACT

OBJECTIVE: Our study aimed to investigate the correlation between intraoperative hypothermia and postoperative delirium (POD) in patients undergoing general anesthesia for gastrointestinal surgery. METHODS: The study comprised 750 participants from the Perioperative Neurocognitive Disorder Risk Factor and Prognosis (PNDRFAP) study database, which ultimately screened 510 individuals in the final analysis. Preoperative cognitive function was evaluated using the Mini-Mental State Examination (MMSE). The occurrence of POD was determined using the Confusion Assessment Method, and the severity of POD was evaluated using the Memorial Delirium Assessment Scale. Logistic regression was employed to scrutinize the association between intraoperative hypothermia and the incidence of POD, and the sensitivity analysis was conducted by introducing adjusted confounding variables. Decision curves and a nomogram model were utilized to assess the predictive efficacy of intraoperative hypothermia for POD. Mediation analysis involving 10,000 bootstrapped iterations was employed to appraise the suggested mediating effect of numeric rating scale (NRS) scores at 24 and 48 h post-surgeries. The receiver-operating characteristic (ROC) was utilized to evaluate the effectiveness of intraoperative hypothermia in predicting POD. RESULTS: In the PNDRFAP study, the occurrence of POD was notably higher in the intraoperative hypothermia group (62.2%) compared to the intraoperative normal body temperature group (9.8%), with an overall POD incidence of 17.6%. Logistic regression analysis, adjusted for various confounding factors (age [40-90], gender, education, MMSE, smoking history, drinking history, hypertension, diabetes, and the presence of cardiovascular heart disease), demonstrated that intraoperative hypothermia significantly increased the risk of POD (OR = 4.879, 95% CI = 3.020-7.882, p < .001). Mediation analyses revealed that the relationship between intraoperative hypothermia and POD was partially mediated by NRS 24 h after surgery, accounting for 14.09% of the association (p = .002). The area under the curve of the ROC curve was 0.685, which confirmed that intraoperative hypothermia could predict POD occurrence to a certain extent. Decision curve and nomogram analyses, conducted using the R package, further substantiated the predictive efficacy of intraoperative hypothermia on POD. CONCLUSION: Intraoperative hypothermia may increase the risk of POD, and this association may be partially mediated by NRS scores 24 h after surgery.


Subject(s)
Delirium , Hypothermia , Intraoperative Complications , Postoperative Complications , Humans , Male , Female , Middle Aged , Aged , Hypothermia/epidemiology , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Delirium/etiology , Delirium/epidemiology , Intraoperative Complications/epidemiology , Intraoperative Complications/etiology , Anesthesia, General/adverse effects , Risk Factors , Digestive System Surgical Procedures/adverse effects , Incidence , Adult
7.
Postgrad Med J ; 2024 May 20.
Article in English | MEDLINE | ID: mdl-38767468

ABSTRACT

For metastatic prostate cancer, androgen deprivation therapy (ADT) is the key strategy to control the disease. However, after 18-24 months of treatment, most patients will progress from metastatic hormone-sensitive prostate cancer (mHSPC) to metastatic castration-resistant prostate cancer (mCRPC) even with ADT. Once patients enter into mCRPC, they face with significant declines in quality of life and a dramatically reduced survival period. Thus, doublet therapy, which combines ADT with new hormone therapy (NHT) or ADT with docetaxel chemotherapy, substitutes ADT alone and has become the "gold standard" for the treatment of mHSPC. In recent years, triplet therapy, which combines ADT with NHT and docetaxel chemotherapy, has also achieved impressive effects in mHSPC. This article provides a comprehensive review of the recent applications of the triplet therapy in the field of mHSPC.

8.
J Multidiscip Healthc ; 17: 2389-2397, 2024.
Article in English | MEDLINE | ID: mdl-38770170

ABSTRACT

Background: Post-stroke Fatigue (PSF) after Intracerebral Hemorrhage (ICH) is a long-term symptom in stroke survivors. However, the pathogenesis of PSF remains inadequately understood and sufficient evidence-based treatments are lacking. Mobile health (mHealth) technology offers a promising approach to expanding access to high-quality and culturally tailored evidence-based mental care. Aim: This study examined the role of mHealth called iHealth in the management of PSF after ICH. Methods: A total of 225 patients diagnosed with intracerebral hemorrhage (ICH) were included in the study and randomly assigned to either the Mobile Health Intervention Group (mHI Group) or the non-Mobile Health Intervention Group (non-mHI). The management involved the utilization of a digital healthcare application named iHealth, which incorporated digital questionnaires, fatigue scale tests, and online videos for the purpose of administering the Patient Fatigue Reporting Measurement Information System (PFRMIS) short form as part of the initial patient assessment following ICH. The study was conducted remotely via video conferencing over a 12-week period in mHI Group, with fatigue assessments being conducted 3 months post-ICH onset in two groups. Results: Following the administration of PSF by iHealth, Univariate Logistic analyses indicated a significant association between fatigue and the type of activity, with patients who were sedentary or did nothing experiencing higher levels of fatigue (ß=2.332, p<0.001; ß=2.517, p<0.001). Multivariate Logistic analyses demonstrated a positive association between the intensity of physical activity and decreased emotional well-being and family support, as well as increased fatigue. (p=0.001, p=0.002, p=0.001). The FSS results demonstrated a significantly reduced incidence of PSF in the MHI group in comparison to non-mHI group following the conclusion of the programme. (13.1% vs 40%, p<0.001). Conclusion: This study explored the effectiveness of the iHealth app for PSF following ICH, indicating that iHealth is a clinically valuable tool that warrants further dissemination.

9.
Prosthet Orthot Int ; 2024 May 21.
Article in English | MEDLINE | ID: mdl-38771762

ABSTRACT

BACKGROUND: Implicit magnitudes and distribution of excessive contact pressures under hand orthoses hinder clinicians from precisely adjusting them to relieve the pressures. To address this, contact pressure under a hand orthosis were analysed using finite element method. METHODS: This paper proposed a method to numerically predict the relatively high magnitudes and critical distribution of contact pressures under hand orthosis through finite element analysis, to identify excessive contact pressure locations. The finite element model was established consisting of the hand, orthosis and bones. The hand and bones were assumed to be homogeneous and elastic bodies, and the orthosis was considered as an isotropic and elastic shell. Two predictions were conducted by assigning either low (fat) or high (skin) material stiffness to the hand model to attain the range of pressure magnitudes. An experiment was conducted to measure contact pressures at the predicted pressure locations. RESULTS: Identical pressure distributions were obtained from both predictions with relatively high pressure values disseminated at 12 anatomical locations. The highest magnitude was found at the thumb metacarpophalangeal joint with the maximum pressure range from 13 to 78 KPa. The measured values were within the predicted range of pressure magnitudes. Moreover, 6 excessive contact pressure locations were identified. CONCLUSIONS: The proposed method was verified by the measurement results. It renders understanding of interface conditions underneath the orthosis to inform clinicians regarding orthosis design and adjustment. It could also guide the development of 3D printed or sensorised orthosis by indicating optimal locations for perforations or pressure sensors.

10.
PLoS One ; 19(5): e0303997, 2024.
Article in English | MEDLINE | ID: mdl-38781252

ABSTRACT

BACKGROUND: The Chinese government has been promoting commercial medical insurance (CMI) in recent decades as it plays an increasingly important role in addressing disease burden, health inequities, and other healthcare challenges. However, compared with developed countries, the CMI is still less fledged with low coverage. OBJECTIVE: This study aims to explore the factors associated with enrollment in CMI, with regards to explicit characteristics (including sociodemographic characteristics and family economic status), latent characteristics (including social security status), and the global incentive compatibility index (including health status), to inform the design of CMI to improve its coverage in China. METHODS: Based on the principal-agent model, we summarized and classified the factors associated with the enrollment in CMI, and then analyzed the data generated from the Chinese General Social Survey in 2015,2018 and 2021 respectively. A comparison of factors regarding sociodemographic characteristics, family economic status, social security status, and health status was conducted between individuals enrolled and unenrolled in CMI using Mann-Whitney U test and Chi-square test. Binary logistic regression analysis was used to explore factors influencing the enrollment status of CMI. RESULTS: Of all individuals, the proportion of enrolled individuals shows an increasing trend year by year, with 8.7%,11.8% and 14.1% enrolled in CMI in 2015,2018 and 2021, respectively. The binary regression analysis further suggested that the factors associated with the enrollment in CMI were consistent in 2015,2018 and 2021.We found that individuals divorced, obese, who had a higher level of education, had non-agricultural household registration, perceived themselves as the upper social status, conducted daily exercise, had more family houses, had a car, had investment activities, or did not have basic health insurance were more likely to be enrolled in CMI. CONCLUSIONS: We identified multidimensional factors associated with the enrollment of CMI, which help inform the government and insurance industry to improve the coverage of CMI.


Subject(s)
Insurance, Health , Humans , China , Insurance, Health/economics , Female , Male , Adult , Middle Aged , Surveys and Questionnaires , Socioeconomic Factors , Young Adult , Adolescent , Aged , Health Status
11.
Front Med (Lausanne) ; 11: 1354514, 2024.
Article in English | MEDLINE | ID: mdl-38784231

ABSTRACT

Background: Crigler-Najjar syndrome (CNS) is caused by mutations in uridine 5'-diphosphate glucuronyltransferase (UGT1A1) resulting in enzyme deficiency and hyperbilirubinemia. Type II CNS patients could respond to phenobarbital treatment and survive. This study presents a rare case of type II CNS. Case summary: The proband was a 29-year-old male patient admitted with severe jaundice. A hepatic biopsy showed bullous steatosis of the peri-central veins of the hepatic lobule, sediment of bile pigment, and mild periportal inflammation with normal liver plate structure. The type II CNS was diagnosed by routine genomic sequencing which found that the proband with the Gry71Arg/Tyr486Asp compound heterozygous mutations in the UGT1A1 gene. After treatment with phenobarbital (180 mg/day), his bilirubin levels fluctuated between 100 and 200 µmol/L for 6 months and without severe icterus. Conclusion: Type II CNS could be diagnosed by routine gene sequencing and treated by phenobarbital.

12.
Nanomaterials (Basel) ; 14(10)2024 May 10.
Article in English | MEDLINE | ID: mdl-38786797

ABSTRACT

A rapid and accurate monitoring of hazardous formaldehyde (HCHO) gas is extremely essential for health protection. However, the high-power consumption and humidity interference still hinder the application of HCHO gas sensors. Hence, zeolitic imidazolate framework-8 (ZIF-8)-loaded Pt-NiO/In2O3 hollow nanofibers (ZPNiIn HNFs) were designed via the electrospinning technique followed by hydrothermal treatment, aiming to enable a synergistic advantage of the surface modification and the construction of a p-n heterostructure to improve the sensing performance of the HCHO gas sensor. The ZPNiIn HNF sensor has a response value of 52.8 to 100 ppm HCHO, a nearly 4-fold enhancement over a pristine In2O3 sensor, at a moderately low temperature of 180 °C, along with rapid response/recovery speed (8/17 s) and excellent humidity tolerance. These enhanced sensing properties can be attributed to the Pt catalysts boosting the catalytic activity, the p-n heterojunctions facilitating the chemical reaction, and the appropriate ZIF-8 loading providing a hydrophobic surface. Our research presents an effective sensing material design strategy for inspiring the development of cost-effective sensors for the accurate detection of indoor HCHO hazardous gas.

13.
Cancer Lett ; 593: 216957, 2024 May 16.
Article in English | MEDLINE | ID: mdl-38762192

ABSTRACT

Circular RNAs (circRNAs) have been implicated in cancer development. However, their regulation, function, and underlying mechanisms of action remain unclear. We found that circHIPK2 was downregulated in colon cancer, and low expression levels of circHIPK2 were associated with high tumor grade and poor patient survival. The expression of circHIPK2 was observed to be regulated by the transcription factor HOXD10, which was downregulated in colon cancer. Consequently, low circHIPK2 expression promoted colon cancer cell proliferation, migration, and invasion in vitro and tumor growth and metastasis in vivo. Mechanistically, circHIPK2 sponges miR-373-3p to upregulate the expression of the tumor suppressor RGMA, leading to the activation of BMP/Smad signaling and, ultimately, the inhibition of colon cancer cells, indicating that circHIPK2 inhibits colon cancer cells through the miR-373-3p/RGMA/BMP pathway. These findings revealed a previously unknown regulation, function, and underlying mechanism of circHIPK2 in cancer cells. Hence, circHIPK2 may have a prognostic value and serve as a potential target for colon cancer treatment.

14.
Food Chem ; 454: 139752, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38815330

ABSTRACT

Ferritin, a vital protein required to store iron in a cage-like structure, is critical for maintaining iron balance. Ferritin can be attacked by free radicals during iron reduction and release, thereby leading to oxidative damage. Whether other biomacromolecules such as casein phosphopeptides (CPP) could influence the ferritin's function in iron oxidation and release and affect the ferritin stability remains unclear. This study aims to investigate the effect of CPP on the ferritin­iron ion interaction, thereby focusing on role of CPP on ferritin stability. Results showed that CPP weakened the iron oxidation activity of ferritin but promoted iron release. Moreover, CPP could effectively chelate iron, capture hydroxyl radicals, and reduce the degradation of ferritin. This study highlights the role of CPP in the ferritin­iron relationship, and lays a foundation for understanding the interaction between ferritin, peptides, and metal ions.

15.
Chem Commun (Camb) ; 60(45): 5828-5831, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38747249

ABSTRACT

The salt metathesis of a boryl-ethynyl lithium salt {[(HCDipN)2]B-CC-Li} with a monochlorosilylene [LSi(:)Cl; L = PhC(NtBu)2] produced an isolable boryl-ethynyl silylene {1; [(HCDipN)2]B-CC-Si(L)}. The Si(II) center in 1 possesses a nonbonding lone pair and forms a covalent bond with the ethynyl group. The characterization of 1 was carried out by multinuclear NMR spectroscopy, single-crystal X-ray structure analysis and DFT calculations. Additionally, a reactivity study of 1 was conducted towards oxygen-containing and aryl C-F substrates.

16.
Angew Chem Int Ed Engl ; : e202407613, 2024 May 12.
Article in English | MEDLINE | ID: mdl-38736299

ABSTRACT

Anion-exchange membrane fuel cells provide the possibility to use platinum group metal-free catalysts, but the anodic hydrogen oxidation reaction (HOR) suffers from sluggish kinetics and its source is still debated. Here, over nickel-tungsten (Ni-W) alloy catalysts, we show that the Ni:W ratio greatly governs the HOR performance in alkaline electrolyte. Experimental and theoretical studies unravel that alloying with W can tune the unpaired electrons in Ni, tailoring the potential of zero charge and the catalytic surface to favor hydroxyl adsorption (OHad). The OHad species coordinately interact with potassium (K+) ions, which break the K+ solvation sheath to leave free water molecules, yielding an improved connectivity of hydrogen-bond networks. Consequently, the optimal Ni17W3 alloy exhibits alkaline HOR activity superior to the state-of-the-art platinum on carbon (Pt/C) catalyst and operates steadily with negligible decay after 10,000 cycles. Our findings offer new understandings of alloyed HOR catalysts and will guide rational design of next-generation catalysts for fuel cells.

17.
iScience ; 27(6): 109811, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38799585

ABSTRACT

Magnesium-ion batteries (MIBs) a strong candidate to set off the second-generation energy storage boom due to their double charge transfer and dendrite-free advantages. However, the strong coulombic force and the huge diffusion energy barrier between Mg2+ and the electrode material have led to need for a cathode material that can enable the rapid and reversible de-insertion of Mg2+. So far, researchers have found that the sulfur-converted cathode materials have a greater application prospect due to the advantages of low price and high specific capacity, etc. Based on these advantages, it is possible to achieve the goal of increasing the magnesium storage capacity and cycling stability by reasonable modification of crystal or morphology. In this review, we focus on the application of a variety of sulfur-converted cathode materials in MIBs in recent years from the perspective of microstructural design, and provide an outlook on current challenges and future development.

18.
Front Psychol ; 15: 1361158, 2024.
Article in English | MEDLINE | ID: mdl-38746924

ABSTRACT

Introduction: Why do some people show more corruption when facing uncertain environment? The present study aimed to give a plausible answer from an evolutionary perspective: this might be rooted in people's different life history strategies (slow vs. fast). Methods: The present study measured the participants' corrupt intentions by a hypothetical scenario and primed the feeling of economic environmental uncertainty by requiring the participants to read economic uncertainty (vs. neutral) materials. Results: It is revealed that the participants with fast life history strategies had stronger corrupt intentions after reading materials about economic uncertainty than reading neutral materials. In addition, the desire for power mediated the interactive effect between life history strategy and economic uncertainty on corrupt intentions for fast life history strategists. Discussion: This finding was discussed for its theoretical and practical implications from the perspective of life history theory.

19.
Front Neurosci ; 18: 1385675, 2024.
Article in English | MEDLINE | ID: mdl-38765669

ABSTRACT

Background: MicroRNAs (miRNAs) have pivotal roles in gene regulation. Circulating miRNAs have been developed as novel candidate non-invasive biomarkers for diagnosis, prognosis, and treatment response for diseases. However, miRNAs that have causal effects on Parkinson's Disease (PD) remain largely unknown. To investigate the causal relationships between miRNAs and PD, here we conduct a Mendelian randomization (MR) study. Methods: This study utilized the summary-level data of respective genome-wide association studies (GWAS) for 2083 miRNAs and seven PD-related outcomes to comprehensively reveal the causal associations between the circulating miRNAs and PD. Two-sample MR design was deployed and the causal effects were estimated with inverse variance weighted, MR-Egger, and weighted median. Comprehensively sensitive analyses were followed, including Cochran's Q test, MR-Egger intercept test, MR-PRESSO, and leave-one-out analysis, to validate the robustness of our results. Finally, we investigated the potential role of the MR significant miRNAs by predicting their target genes and functional enrichment analysis. Results: Inverse variance weighted estimates suggested that two miRNAs, miR-205-5p (ß = -0.46, 95%CI: -0.690 to -0.229, p = 9.3 × 10-5) and miR-6800-5p (ß = -0.389, 95%CI: -0.575 to -0.202, p = 4.32 × 10-5), significantly decreased the rate of cognitive decline among PD patients. In addition, eight miRNAs were nominally associated with more than three PD-related outcomes each. No significant heterogeneity of instrumental variables or horizontal pleiotropy was found. Gene Ontology (GO) analysis showed that the targets of these causal miRNAs were significantly enriched in cell cycle, apoptotic, and aging pathways. Conclusion: This MR study identified two miRNAs whose genetically regulated expression might have a causal role in the development of PD dementia. Our findings provided potential miRNA biomarkers to make better and early diagnoses and risk assessments of PD.

20.
PeerJ ; 12: e17362, 2024.
Article in English | MEDLINE | ID: mdl-38766486

ABSTRACT

Backgrounds: TBC1D family members (TBC1Ds) are a group of proteins that contain the Tre2-Bub2-Cdc16 (TBC) domain. Recent studies have shown that TBC1Ds are involved in tumor growth, but no analysis has been done of expression patterns and prognostic values of TBC1Ds in hepatocellular carcinoma (HCC). Methods: The expression levels of TBC1Ds were evaluated in HCC using the TIMER, UALCN and Protein Atlas databases. The correlation between the mRNA levels of TBC1Ds and the prognosis of patients with HCC in the GEPIA database was then analyzed. An enrichment analysis then revealed genes that potentially interact with TBC1Ds. The correlation between levels of TBC1Ds and tumor-infiltrating immune cells (TIICs) in HCC were studied using the TIMER 2.0 database. Finally, a series of in vitro assays verified the role of TBC1Ds in HCC progression. Results: This study revealed the upregulated expression of TBC1Ds in HCC and the strong positive correlation between the mRNA levels of TBC1Ds and poor prognosis of patients with HCC. The functions of TBC1Ds were mainly related to autophagy and the AMPK pathway. There was also a significant correlation between level of TBC1Ds and tumor-infiltrating immune cells (TIICs) in HCC. The promoting role of TBC1Ds in HCC progression was verified in vitro assays. Conclusion: The results of this analysis indicate that TBC1Ds may serve as new biomarkers for early diagnosis and treatment of HCC.


Subject(s)
Carcinoma, Hepatocellular , GTPase-Activating Proteins , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/immunology , Carcinoma, Hepatocellular/metabolism , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Liver Neoplasms/immunology , Liver Neoplasms/metabolism , Prognosis , GTPase-Activating Proteins/genetics , GTPase-Activating Proteins/metabolism , Gene Expression Regulation, Neoplastic , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Autophagy/genetics , RNA, Messenger/genetics , RNA, Messenger/metabolism , Cell Line, Tumor
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