Aspirin suppresses hepatocellular carcinoma progression by inhibiting platelet activity.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common malignant liver disease in the world. Platelets (PLTs) are known to play a key role in the maintenance of liver homeostasis and the pathophysiological processes of a variety of liver diseases. Aspirin is the most classic antiplatelet agent. However, the molecular mechanism of platelet action and whether aspirin can affect HCC progression by inhibiting platelet activity need further study. AIM: To explore the impact of the antiplatelet effect of aspirin on the development of HCC. METHODS: Platelet-rich plasma, platelet plasma, pure platelet, and platelet lysate were prepared, and a coculture model of PLTs and HCC cells was established. CCK-8 analysis, apoptosis analysis, Transwell analysis, and real-time polymerase chain reaction (RT-PCR) were used to analyze the effects of PLTs on the growth, metastasis, and inflammatory microenvironment of HCC. RT-PCR and Western blot were used to detect the effects of platelet activation on tumor-related signaling pathways. Aspirin was used to block the activation and aggregation of PLTs both in vitro and in vivo, and the effect of PLTs on the progression of HCC was detected. RESULTS: PLTs significantly promoted the growth, invasion, epithelial-mesenchymal transition, and formation of an inflammatory microenvironment in HCC cells. Activated PLTs promoted HCC progression by activating the mitogen-activated protein kinase/protein kinase B/signal transducer and activator of transcription three (MAPK/ AKT/STAT3) signaling axis. Additionally, aspirin inhibited HCC progression in vitro and in vivo by inhibiting platelet activation. CONCLUSION: PLTs play an important role in the pathogenesis of HCC, and aspirin can affect HCC progression by inhibiting platelet activity. These results suggest that antiplatelet therapy has promising application prospects in the treatment and combined treatment of HCC.

Increasing the Maximum Detectable Flow Velocity in High-Frequency Ultrasound Vector Doppler Imaging.

High-frequency ultrasound (HFUS; >30 MHz) Doppler imaging has been widely used in the imaging of small animals and humans because of its high resolution. Vector Doppler imaging (VDI) has certain advantages for visualizing complex flow patterns independent of the Doppler angle. However, no commercial HFUS VDI system is currently available; therefore, several studies have connected an ultrasound research platform (Verasonics Vantage 256) with an HFUS array transducer for HFUS VDI. Unfortunately, the maximum frame rate of this system is only 10 kHz at an operational frequency of 40 MHz because of limitations related to data transmission hardware, thereby restricting the maximum detectable velocity of Doppler measurements. To address this drawback, in the present study, an electrocardiography (ECG)-gating-based HFUS VDI system was developed to avoid Doppler flow aliasing in data acquisition by ultrasound research platform at its maximum frame rate of 10 kHz. The developed method aligns all tilted plane waves with the ECG R-wave, which avoids the trade-off between frame rate and tilted angles number in conventional VDI. The performance of the proposed data acquisition method in HFUS VDI was verified using a steady-flow phantom, for which estimation errors were less than 10% under different flow settings. In animal studies, peak flow velocities in the carotid artery, left ventricle, and aortic arch of wild-type mice were measured (approximately 55, 655, and 765 mm/s, respectively). Also, the HFUS VDI from the mitral regurgitation mice model was obtained to present the complex flow patterns through the proposed method. In contrast to the conventional method, no Doppler aliasing occurs in the proposed method because the frame rate is sufficient. The experimental results indicate the developed HFUS VDI has the potential to become a useful tool for vector flow visualization in small animals, even under a high flow velocity.

Long Short-Term Memory Networks' Application on Typhoon Wave Prediction for the Western Coast of Taiwan.

Huge waves caused by typhoons often induce severe disasters along coastal areas, making the effective prediction of typhoon-induced waves a crucial research issue for researchers. In recent years, the development of the Internet of Underwater Things (IoUT) has rapidly increased the prediction of oceanic environmental disasters. Past studies have utilized meteorological data and feedforward neural networks (e.g., BPNN) with static network structures to establish short lead time (e.g., 1 h) typhoon wave prediction models for the coast of Taiwan. However, sufficient lead time for prediction remains essential for preparedness, early warning, and response to minimize the loss of lives and properties during typhoons. The aim of this research is to construct a novel long lead time typhoon-induced wave prediction model using Long Short-Term Memory (LSTM), which incorporates a dynamic network structure. LSTM can capture long-term information through its recurrent structure and selectively retain necessary signals using memory gates. Compared to earlier studies, this method extends the prediction lead time and significantly improves the learning and generalization capability, thereby enhancing prediction accuracy markedly.

The association between air pollution and obesity: an umbrella review of meta-analyses and systematic reviews.

The objective of this umbrella review was to investigate comprehensive and synthesized evidence of the association between ambient air pollution and obesity based on the current systematic reviews and meta-analyses. Related studies from databases including PubMed, EMBASE, Web of Science, and the Cochrane Library, published before July 16, 2023, were considered in the analysis. All selected systematic reviews and meta-analyses were included in accordance with PRISMA guidelines. The risk of bias and the methodological quality were evaluated using the AMSTAR 2 tool. The protocol for this umbrella review was documented in PROSPERO with the registration number: CRD42023450191. This umbrella review identified 7 studies, including 5 meta-analyses and 2 systematic reviews, to assess the impacts of air pollutants on obesity. Commonly examined air pollutants included PM1, PM2.5, PM10, NO2, SO2, O3. Most of the included studies presented that air pollution exposure was positively associated with the increased risk of obesity. The impact of air pollution on obesity varied by different ambient air pollutants. This study provided compelling evidence that exposure to air pollution had a positive association with the risk of obesity. These findings further indicate the importance of strengthening air pollution prevention and control. Future studies should elucidate the possible mechanisms and pathways linking air pollution to obesity.

Neuroimaging and clinical features of bilateral Wallerian degeneration of middle cerebellar peduncles subsequent to pontine infarction.

OBJECTIVE: Wallerian degeneration (WD) of the middle cerebellar peduncles (MCPs) following pontine infarction is a rare secondary degenerative neurological condition. Due to its infrequency, there is limited research on its characteristics. METHODS: This study aims to present three cases of WD of MCPs following pontine infarction and to analyze the prognosis, clinical manifestations, and neuroimaging features by amalgamating our cases with previously reported ones. RESULTS: The cohort consisted of 25 cases, comprising 18 men and 7 women aged 29 to 77 years (mean age: 66.2 years). The majority of patients (94%) exhibit risk factors for cerebrovascular disease, with hypertension being the primary risk factor. Magnetic resonance imaging (MRI) can detect WD of MCPs within a range of 21 days to 12 months following pontine infarction. This degeneration is characterized by bilateral symmetric hyperintensities on T2/FLAIR-weighted images (WI) lesions in the MCPs. Moreover, restricted diffusion, with hyperintensity on diffusion-weighted imaging (DWI) and low apparent diffusion coefficient (ADC) signal intensity may be observed as early as 21 days after the infarction. Upon detection of WD, it was observed that 20 patients (80%) remained asymptomatic during subsequent clinic visits, while four (16%) experienced a worsening of pre-existing symptoms. CONCLUSIONS: These findings underscore the importance of neurologists enhancing their understanding of this condition by gaining fresh insights into the neuroimaging characteristics, clinical manifestations, and prognosis of individuals with WD of bilateral MCPs.

HEARTSVG: a fast and accurate method for identifying spatially variable genes in large-scale spatial transcriptomics.

Identifying spatially variable genes (SVGs) is crucial for understanding the spatiotemporal characteristics of diseases and tissue structures, posing a distinctive challenge in spatial transcriptomics research. We propose HEARTSVG, a distribution-free, test-based method for fast and accurately identifying spatially variable genes in large-scale spatial transcriptomic data. Extensive simulations demonstrate that HEARTSVG outperforms state-of-the-art methods with higher F 1 scores (average F 1 Score=0.948), improved computational efficiency, scalability, and reduced false positives (FPs). Through analysis of twelve real datasets from various spatial transcriptomic technologies, HEARTSVG identifies a greater number of biologically significant SVGs (average AUC = 0.792) than other comparative methods without prespecifying spatial patterns. Furthermore, by clustering SVGs, we uncover two distinct tumor spatial domains characterized by unique spatial expression patterns, spatial-temporal locations, and biological functions in human colorectal cancer data, unraveling the complexity of tumors.

Foveapeltis gen. nov., an unusual cleroid genus with large hypomeral cavities from mid-Cretaceous amber (Coleoptera: Cleroidea).

Beetles have a remote evolutionary history dating back to the Carboniferous, with Mesozoic fossils playing a pivotal role in elucidating the early evolution of extant families. Despite their exceptional preservation in amber, deciphering the systematic positions of Mesozoic trogossitid-like beetles remains challenging. Here, we describe and illustrate a new trogossitid-like lineage from mid-Cretaceous Kachin amber, Foveapeltis rutai Li, Kolibác, Liu & Cai, gen. et sp. nov. Foveapeltis stands out within the Cleroidea due to the presence of a significant large cavity on each hypomeron. While the exact phylogenetic placement of Foveapeltis remains uncertain, we offer a discussion on its potential affinity based on our constrained phylogenetic analyses.

The impact of flooding from the Minjiang River on the succession of harmful algal blooms (HABs) caused by diatoms in China's offshore waters.

This study examines diatom assemblages in the Matsu Archipelago, an area influenced by Minjiang River runoff. It focuses on harmful algal blooms (HABs) that occurred between August 2021 and July 2022. Utilizing 18S rRNA metabarcoding and microscopic analysis, we observed a significant diatom bloom during early summer runoff, peaking at 5 × 105 cells L-1. The research reveals dynamic community changes during the runoff season, with dominant genera including Pseudo-nitzschia, Chaetoceros, and Skeletonema. Skeletonema cell density correlated with NO3 levels, Chaetoceros had a slight PO4 affinity, and Pseudo-nitzschia showed a negative correlation with Skeletonema. Pseudo-nitzschia, which prefers high light and pH conditions, had notably high concentrations in the flood season and in the autumn. In both, it was dominated by potential toxin-producing species - P. multistriata and P. pungens during the flooding, and P. cuspidate in the autumn. These findings highlight the intricate relationship between diatom dynamics and environmental factors, providing essential insights for managing HABs, especially Pseudo-nitzschia species, amidst environmental changes.

Composition, distribution, and risk assessment of heavy metals in large-scale river water on the Tibetan Plateau.

Heavy metals present in aquatic ecosystems constitute a significant threat to both the environment and human health. In this study, we analyzed various heavy metals (As, Cr, Co, Ni, Cu, Mo, Cd, Pb and Sb) using extensive surface water samples collected from the Tibetan Plateau in 2021 and 2023. Results showed that downstream water samples exhibited higher content (mean 12.6 µg/L) of heavy metals compared to those from the glacier basins. It is noteworthy that heavy metal content varied significantly both in the glacier basin and downstream (4.6-29.1 µg/L and 7.8-55.2 µg/L, respectively). However, elevated concentrations at certain sites (e.g., Saga County and Dangque Zangbu River) were primarily attributed to the disproportionate contribution of individual heavy metals, possibly stemming from specific human activities or natural conditions. In the glacier basin, only Cr exhibited a decreasing trend in enrich factors (EF) with increasing Sc concentration, whereas, in the downstream areas, most elements displayed a declining trend. Furthermore, apart from a few sampling sites, heavy metal concentrations in the glacier basin remained relatively balanced, suggesting that these metals predominantly originate from natural sources. The values of potential ecological risk for an individual element (Eri) and potential ecological risk index (PER) indicate that the ecological and human risks associated with almost heavy metals (except As) in the aquatic ecosystem are minimal. ENVIRONMENTAL IMPLICATION: Heavy metals in aquatic ecosystems pose a significant threat to ecological and human health. Due to delicate ecological balance of the Tibetan Plateau and its critical role as a water resource, we analyzed various heavy metals (As, Cr, Co, Ni, Cu, Mo, Cd, Pb and Sb) concentrations and EF in land surface river water, to find out the pollution levels and possible sources of heavy metals in the aquatic ecosystems. The results of risk assessment showed that the prevention and management of arsenic in Tibetan Plateau needs attention, but most heavy metals pose no threaten to ecological and human health.

Application of Phosphorylated Tau for Predicting Outcomes Among Sudden Cardiac Arrest Survivors.

BACKGROUND: Phosphorylated Tau (p-Tau), an early biomarker of neuronal damage, has emerged as a promising candidate for predicting neurological outcomes in cardiac arrest (CA) survivors. Despite its potential, the correlation of p-Tau with other clinical indicators remains underexplored. This study assesses the predictive capability of p-Tau and its effectiveness when used in conjunction with other predictors. METHODS: In this single-center retrospective study, 230 CA survivors had plasma and brain computed tomography scans collected within 24 h after the return of spontaneous circulation (ROSC) from January 2016 to June 2023. The patients with prearrest Cerebral Performance Category scores ≥ 3 were excluded (n = 33). The neurological outcomes at discharge with Cerebral Performance Category scores 1-2 indicated favorable outcomes. Plasma p-Tau levels were measured using an enzyme-linked immunosorbent assay, diastolic blood pressure (DBP) was recorded after ROSC, and the gray-to-white matter ratio (GWR) was calculated from brain computed tomography scans within 24 h after ROSC. RESULTS: Of 197 patients enrolled in the study, 54 (27.4%) had favorable outcomes. Regression analysis showed that higher p-Tau levels correlated with unfavorable neurological outcomes. The levels of p-Tau were significantly correlated with DBP and GWR. For p-Tau to differentiate between neurological outcomes, an optimal cutoff of 456 pg/mL yielded an area under the receiver operating characteristic curve of 0.71. Combining p-Tau, GWR, and DBP improved predictive accuracy (area under the receiver operating characteristic curve = 0.80 vs. 0.71, p = 0.008). CONCLUSIONS: Plasma p-Tau levels measured within 24 h following ROSC, particularly when combined with GWR and DBP, may serve as a promising biomarker of neurological outcomes in CA survivors, with higher levels predicting unfavorable outcomes.

Real-World Clinical Performance of a Novolimus-Eluting Stent Versus a Sirolimus-Eluting Stent.

INTRODUCTION: The DESyne novolimus-eluting coronary stent (NES) is a new-generation drug-eluting stent (DES) that is widely used, but clinical data are rarely reported for this stent. We compared the safety and effectiveness of the DESyne NES and the Orsiro bioresorbable polymer sirolimus-eluting stent (SES) in patients undergoing percutaneous coronary intervention (PCI). METHODS: This was a retrospective, single-center, observational study. Between July 2017 and December 2022, patients who presented with chronic or acute coronary syndrome undergoing PCI with DESyne NES or Orsiro SES were consecutively enrolled in the present study. The primary endpoint, major adverse cardiovascular event (MACE), was a composite of cardiovascular death, target-vessel myocardial infarction, or clinically driven target-lesion revascularization. RESULTS: A total of 776 patients (age 68.8 ± 12.2; 75.9% male) undergoing PCI were included. Overall, 231 patients with 313 lesions received NES and 545 patients with 846 lesions received SES. During a follow-up duration of 784 ± 522 days, the primary endpoint occurred in 10 patients (4.3%) in the NES group and in 36 patients (6.6%) in the SES group. After multivariate adjustment, the risk of MACE did not significantly differ between groups (NES vs. SES, hazard ratio 0.74, 95% CI, 0.35-1.55, p = 0.425). The event rate of individual components of the primary endpoint was comparable between the two groups. CONCLUSIONS: Favorable and similar clinical outcomes were observed in patients undergoing PCI with either NES or SES in a medium-term follow-up duration. Future studies with adequately powered clinical endpoints are required for further evaluation.

Electronic Medical Record-Based Nudge Intervention to Increase Comprehensive Molecular Genotyping in Patients With Metastatic Non-Small Cell Lung Cancer: Results From a Prospective Clinical Trial.

PURPOSE: Less than half of the patients with newly diagnosed metastatic non-small cell lung cancer (NSCLC) undergo comprehensive molecular testing. We designed an electronic medical record (EMR)-based "nudge intervention" to prompt plasma-based molecular testing at the time of initial medical oncology consultation. METHODS: A nonrandomized prospective trial was conducted at the University of Pennsylvania's academic practice and two affiliated community practices. Molecular genotyping was performed by tissue- and/or plasma-based next generation sequencing methods. Comprehensive testing was defined as testing for EGFR, ALK, BRAF, ROS1, MET, RET, KRAS, and NTRK. Guideline-concordant treatment was defined as the use of the appropriate first-line (1L) therapy as per the National Comprehensive Cancer Network (NCCN) guidelines. Proportion of patients with comprehensive molecular genotyping results available at any time, molecular results available before 1L therapy, and guideline-concordant 1L treatment were compared between the preintervention and postintervention cohorts using Fisher's exact test or Pearson's chi-squared test. RESULTS: Five hundred and thirty-three patients were included, 376 in the preintervention cohort and 157 in the postintervention cohort. After implementation of the EMR-based nudge, a higher proportion of patients underwent comprehensive molecular testing in the postintervention versus the preintervention cohort (100% v 88%, P = <.001), had results of comprehensive molecular testing available before initiating 1L treatment (97.3% v 91.6%, P = .026), and received NCCN guideline-concordant care (89.8% v 78.2%, P = .035). CONCLUSION: Across three practice sites in a large health system, implementation of a provider team-focused EMR-based nudge intervention was feasible, and led to a higher number of patients with NSCLC undergoing comprehensive molecular genotyping. These findings demonstrate that behavioral nudges can promote molecular testing and should be studied further as a tool to improve guideline-concordant care in both community and academic sites.

Strong, anti-swelling, and biodegradable seaweed-based straws with surface mineralized CaCO3 armor.

While the extensive utilization of disposable plastic straws has resulted in significant environmental issues such as microplastics and soil and ocean pollution, the quest for alternative straws for versatile use remains a formidable challenge. Here, drawing inspiration from naturally water-resistant materials such as bones and sea urchins, we have developed seaweed-based straws with significantly improved water resistance and mechanical strength via in-situ mineralization of CaCO3 on their surfaces. Specifically, the COO- groups on the G (α-L-guluronate) blocks of alginate were employed to establish a robust cross-linked network, while the COO- groups on the M (ß-D-mannuronate) blocks attracted free Ca2+ through electrostatic forces, thereby promoting CaCO3 nucleation. This effectively prevents COOH groups from hydrating, reducing swelling, and results in the fabrication of nano- to micron-sized CaCO3 particles that reinforce the structure without compromising the cross-linked network. Compared with the control group, the S5% sample (prepared with 5 % Na2CO3 solution) exhibited a 102 % increase in water contact angle, a 35 % decrease in swelling degree, and a 35.5 % and 37.5 % increase in ultimate flexural and tensile stress, respectively. Furthermore, the potential use of these straws as a waste for heavy metal adsorption was investigated, addressing environmental concerns while demonstrating economic feasibility.

Effect of measurement procedure errors on assessing lung fluid via remote dielectric sensing system.

The study assessed the impact of procedural errors on the remote dielectric sensing system (ReDS), a non-invasive lung fluid assessment technology, in an Asian cohort. Healthy volunteers underwent ReDS measurements following manufacturer's instructions, with two consecutive measurements one minute apart. A subset of 20 participants had modified procedure settings. Reliability was measured using intraclass correlation coefficient (ICC). The study included 86 healthy volunteers, and all ReDS measurements fell within the recommended normal range. The intra-rater reliability of ReDS measurements was excellent, with an ICC of 0.968. Among the subset of 20 subjects, deviations in height and weight did not significantly affect ReDS values. However, deviations in chest size by ± 3 cm had a noticeable impact on ReDS measures, and incorrect station selection led to fluctuations in ReDS readings. In conclusion, the ReDS system demonstrated excellent intra-rater reliability and applicability in an Asian cohort. Procedural errors, such as chest size measurement and station selection, significantly influenced ReDS measurements. Adherence to standardized operating procedures is crucial to ensure accurate and consistent results. These findings highlight the importance of adherence to manufacturer instructions when utilizing ReDS for lung fluid assessment, thereby enhancing its reliability and clinical applicability.

Predictors and Risk Score for Immune Checkpoint-Inhibitor-Associated Myocarditis Severity.

Background: Immune-checkpoint inhibitors (ICI) are associated with life-threatening myocarditis but milder presentations are increasingly recognized. The same autoimmune process that causes ICI-myocarditis can manifest concurrent generalized myositis, myasthenia-like syndrome, and respiratory muscle failure. Prognostic factors for this "cardiomyotoxicity" are lacking. Methods: A multicenter registry collected data retrospectively from 17 countries between 2014-2023. A multivariable cox regression model (hazard-ratio(HR), [95%confidence-interval]) was used to determine risk factors for the primary composite outcome: severe arrhythmia, heart failure, respiratory muscle failure, and/or cardiomyotoxicity-related death. Covariates included demographics, comorbidities, cardio-muscular symptoms, diagnostics, and treatments. Time-dependent covariates were used and missing data were imputed. A point-based prognostic risk score was derived and externally validated. Results: In 748 patients (67% male, age 23-94), 30-days incidence of the primary composite outcome, cardiomyotoxic death, and overall death were 33%, 13%, and 17% respectively. By multivariable analysis, the primary composite outcome was associated with active thymoma (HR=3.60[1.93-6.72]), presence of cardio-muscular symptoms (HR=2.60 [1.58-4.28]), low QRS-voltage on presenting electrocardiogram (HR for ≤0.5mV versus >1mV=2.08[1.31-3.30]), left ventricular ejection fraction (LVEF) <50% (HR=1.78[1.22-2.60]), and incremental troponin elevation (HR=1.86 [1.44-2.39], 2.99[1.91-4.65], 4.80[2.54-9.08], for 20, 200 and 2000-fold above upper reference limit, respectively). A prognostic risk score developed using these parameters showed good performance; 30-days primary outcome incidence increased gradually from 3.9%(risk-score=0) to 81.3%(risk-score≥4). This risk-score was externally validated in two independent French and US cohorts. This risk score was used prospectively in the external French cohort to identify low risk patients who were managed with no immunosuppression resulting in no cardio-myotoxic events. Conclusions: ICI-myocarditis can manifest with high morbidity and mortality. Myocarditis severity is associated with magnitude of troponin, thymoma, low-QRS voltage, depressed LVEF, and cardio-muscular symptoms. A risk-score incorporating these features performed well. Trial registration number: NCT04294771 and NCT05454527.

Programmed Intermittent Epidural Bolus Reduces Workloads in Labor Analgesia: A Single Center's Experience.

Background and Objectives: Labor epidural analgesia can be maintained through programmed intermittent epidural bolus (PIEB), continuous epidural infusion (CEI), or patient-controlled epidural analgesia (PCEA). Our department changed from CEI+PCEA to PIEB+PCEA as the maintenance method. The higher hourly dose setting in the current regimen brought to our concern that side effects would increase with proportional staff workloads. This study aimed to investigate the validity of our proposal that PIEB+PCEA may function as a feasible tool in reducing the amount of work in the obstetrics anesthesia units. Materials and methods: This 2-year retrospective review included parturients with vaginal deliveries under epidural analgesia. We compared the staff burden before and after the switch from CEI (6 mL/h, PCEA 6 mL lockout 15 min, group A) to PIEB (8 mL/h, PCEA 8 mL lockout 10 min, group B). The primary outcome was the difference of proportion of parturients requiring unscheduled visits between groups. Side effects and labor and neonatal outcomes were compared. Results: Of the 694 parturients analyzed, the proportion of those requiring unscheduled visits were significantly reduced in group B (20.8% vs. 27.7%, chi-square test, p = 0.033). The multivariate logistic regression showed that PIEB was associated with fewer unscheduled visits than CEI (OR = 0.53, 95% CI [0.36-0.80], p < 0.01). Group B exhibited a significantly lower incidence of asymmetric blockade, as well as motor blockade. In nulliparous subjects, obstetric anal sphincter injury occurred less frequently when PIEB+PCEA was used. Significantly more multiparous women experienced vacuum extraction delivery in group B than in group A, and they had a longer second stage of labor. Conclusions: The PIEB+PCEA protocol in our study reduced workloads in labor epidural analgesia as compared to CEI+PCEA, despite that a higher dose of analgesics was administered. Future studies are warranted to investigate the effect of manipulating the PIEB settings on the labor outcomes.

[Relationship Between Cerebrovascular Reactivity and Depression in Patients With End-Stage Renal Disease].

Objective To investigate the relationship between cerebrovascular reactivity (CVR) and emotional disorders in the patients undergoing continuous hemodialysis for end-stage renal disease (ESRD).Methods The clinical data of the ESRD patients undergoing continuous hemodialysis were collected.Anxiety and depression of the patients were assessed by the Hamilton anxiety scale (HAMA) and Beck depression inventory,respectively.The cerebral hemodynamic changes during the breath holding test were monitored by transcranial Doppler sonography,and the breath-holding index (BHI) was calculated.The BHI≥0.69 and BHI<0.69 indicate normal CVR and abnormal CVR,respectively.Binary Logistic regression was employed to analyze the factors affecting the depressive state of ESRD patients.Results The group with abnormal CVR exhibited higher total cholesterol level (P=0.010),low density lipoprotein level (P=0.006),and incidence of depression (P=0.012) than the group with normal CVR.Compared with the non-depression group,the depression group displayed prolonged disease course (P=0.039),reduced body mass index (P=0.048),elevated HAMA score (P=0.001),increased incidence of anxiety (P<0.001),decreased BHI (P=0.015),and increased incidence of abnormal CVR (P=0.012).Binary Logistic regression analysis indicated anxiety as a contributing factor (OR=22.915,95%CI=2.653-197.956,P=0.004) and abnormal CVR as a risk factor (OR=0.074,95%CI=0.008-0.730,P=0.026) for depression.Conclusion Impaired CVR could pose a risk for depression in the patients with ESRD.

Specific and efficient knockdown of intracellular miRNA using partially neutralized phosphate-methylated DNA oligonucleic acid-loaded mesoporous silica nanoparticles.

Antisense oligonucleotides (ASOs) are molecules used to regulate RNA expression by targeting specific RNA sequences. One specific type of ASO, known as neutralized DNA (nDNA), contains site-specific methyl phosphotriester (MPTE) linkages on the phosphate backbone, changing the negatively charged DNA phosphodiester into a neutralized MPTE with designed locations. While nDNA has previously been employed as a sensitive nucleotide sequencing probe for the PCR, the potential of nDNA in intracellular RNA regulation and gene therapy remains underexplored. Our study aims to evaluate the regulatory capacity of nDNA as an ASO probe in cellular gene expression. We demonstrated that by tuning MPTE locations, partially and intermediately methylated nDNA loaded onto mesoporous silica nanoparticles (MSNs) can effectively knock down the intracellular miRNA, subsequently resulting in downstream mRNA regulation in colorectal cancer cell HCT116. Additionally, the nDNA ASO-loaded MSNs exhibit superior efficacy in reducing miR-21 levels over 72 hours compared to the efficacy of canonical DNA ASO-loaded MSNs. The reduction in the miR-21 level subsequently resulted in the enhanced mRNA levels of tumour-suppressing genes PTEN and PDCD4. Our findings underscore the potential of nDNA in gene therapies, especially in cancer treatment via a fine-tuned methylation location.

Combined JAK inhibition and PD-1 immunotherapy for non-small cell lung cancer patients.

Persistent inflammation driven by cytokines such as type-one interferon (IFN-I) can cause immunosuppression. We show that administration of the Janus kinase 1 (JAK1) inhibitor itacitinib after anti-PD-1 (programmed cell death protein 1) immunotherapy improves immune function and antitumor responses in mice and results in high response rates (67%) in a phase 2 clinical trial for metastatic non-small cell lung cancer. Patients who failed to respond to initial anti-PD-1 immunotherapy but responded after addition of itacitinib had multiple features of poor immune function to anti-PD-1 alone that improved after JAK inhibition. Itacitinib promoted CD8 T cell plasticity and therapeutic responses of exhausted and effector memory-like T cell clonotypes. Patients with persistent inflammation refractory to itacitinib showed progressive CD8 T cell terminal differentiation and progressive disease. Thus, JAK inhibition may improve the efficacy of anti-PD-1 immunotherapy by pivoting T cell differentiation dynamics.