Triple Aspiration Versus Conventional Aspiration Techniques: A Randomized In-Vitro Evaluation.

BACKGROUND AND PURPOSE: A single aspiration maneuver using a large volume syringe is a common and effective technique for aspiration thrombectomy. Multiple aspiration cycles using large aspiration syringes has been proposed as a means to improve efficacy over single aspiration. In this study, we sought to investigate the efficacy of a "triple aspiration technique" where a large volume syringe is cycled three times prior to catheter retraction during aspiration thrombectomy. MATERIALS AND METHODS: A 3D-printed adult vasculature was used as a benchtop thrombectomy platform. Fibrin-rich and red blood cell-rich clots were prepared in centrifuge tubes using human plasma, red blood cells, and calcium chloride. Next, clots were placed in the carotid terminus of the model, and the performances of three different aspiration techniques-triple syringe, single syringe, and continuous pump aspiration-were compared in a randomized manner (1:1:1). Outcomes of interest included first-pass efficacy (FPE), complete clot removal (final mTICI 2c/3), the number of thrombectomy attempts to achieve mTICI 2c/3, vacuum pressure, and distal embolization. The distal emboli were detected using a 70-micron cell strainer placed at the outflow of the model and quantified using an image processing algorithm. The vacuum pressures were measured using a pressure transducer (Honeywell, NC, USA). RESULTS: A total of 102 replicates were performed, 34 for each technique. The triple aspiration technique provided a significantly higher rate of FPE than the syringe and pump aspiration techniques (67.6% vs. 41.1%, p= 0.02). Additionally, the triple aspiration technique achieved complete clot removal with a significantly lower number of thrombectomy attempts compared to single syringe aspiration (1.2 ± 0.5 vs. 1.8 ± 0.8, p=0.005). The triple aspiration technique generated significantly higher vacuum pressure than both the single syringe and vacuum pump aspiration (28.3 ± 0.2 vs. 27.2 ± 0.3 (p= 0.002) and 26.2 ± 0.4 (p=0.001), respectively). The differences in complete clot removal and distal embolization parameters were not statistically significantly different across the groups. CONCLUSIONS: Our findings suggest that the triple aspiration technique can improve FPE rates and vacuum pressure in aspiration thrombectomy. Further studies are needed to examine the safety and efficacy of triple aspiration in the clinical setting. ABBREVIATIONS: AcommA = anterior communicating artery; FPE = first pass efficacy; ICA = internal carotid artery; MCA = middle cerebral artery; MT = mechanical thrombectomy; mTICI = modified thrombolysis in cerebral infarction scale; PcommA = posterior communicating artery.

Liver stiffness measurement by magnetic resonance elastography predicts cirrhosis and decompensation in alcohol-related liver disease.

PURPOSE: To evaluate magnetic resonance elastography (MRE)-based liver stiffness measurement as a biomarker to predict the onset of cirrhosis in early-stage alcohol-related liver disease (ALD) patients, and the transition from compensated to decompensated cirrhosis in ALD. METHODS: Patients with ALD and at least one MRE examination between 2007 and 2020 were included in this study. Patient demographics, liver chemistries, MELD score (within 30 days of the first MRE), and alcohol abstinence history were collected from the electronic medical records. Liver stiffness and fat fraction were measured. Disease progression was assessed in the records by noting cirrhosis onset in early-stage ALD patients and decompensation in those initially presenting with compensated cirrhosis. Nomograms and cut-off values of liver stiffness, derived from Cox proportional hazards models were created to predict the likelihood of advancing to cirrhosis or decompensation. RESULTS: A total of 182 patients (132 men, median age 57 years) were included in this study. Among 110 patients with early-stage ALD, 23 (20.9%) developed cirrhosis after a median follow-up of 6.2 years. Among 72 patients with compensated cirrhosis, 33 (45.8%) developed decompensation after a median follow-up of 4.2 years. MRE-based liver stiffness, whether considered independently or adjusted for age, alcohol abstinence, fat fraction, and sex, was a significant and independent predictor for both future cirrhosis (Hazard ratio [HR] = 2.0-2.2, p = 0.002-0.003) and hepatic decompensation (HR = 1.2-1.3, p = 0.0001-0.006). Simplified Cox models, thresholds, and corresponding nomograms were devised for practical use, excluding non-significant or biased variables. CONCLUSIONS: MRE-based liver stiffness assessment is a useful predictor for the development of cirrhosis or decompensation in patients with ALD.

Alginate oligosaccharide improves 5-fluorouracil-induced intestinal mucositis by enhancing intestinal barrier and modulating intestinal levels of butyrate and isovalerate.

Chemotherapy-induced mucositis (CIM) is the typical side effect of chemotherapy. This study investigates the potential of alginate oligosaccharide (AOS) in ameliorating CIM induced by 5-fluorouracil (5-FU) in a murine model and its underlying mechanisms. AOS effectively mitigated body weight loss and histopathological damage, modulated inflammatory cytokines and attenuated the oxidative stress. AOS restored intestinal barrier integrity through enhancing expression of tight junction proteins via MLCK signaling pathway. AOS alleviated intestinal mucosal damage by inhibiting TLR4/MyD88/NF-κB signaling pathway, downregulating the pro-apoptotic protein Bax and upregulating the anti-apoptotic protein Bcl-2. Moreover, AOS significantly enriched intestinal Akkermansiaceae and increased the production of short-chain fatty acids (SCFAs), most notably butyrate and isovalerate. Pre-treatment with butyrate and isovalerate also alleviated 5-FU-induced CIM. In conclusion, AOS effectively mitigated CIM through strenghthening intestinal barrier, attenuating inflammation, and modulating gut microbiota and intestianl levels of butyrate and isovalerate. These finding indicate that AOS could be potentially utilized as a supplemental strategy for prevention or mitigation of CIM.

B3galt5 functions as a PXR target gene and regulates obesity and insulin resistance by maintaining intestinal integrity.

Pregnane X receptor (PXR) has been reported to regulate glycolipid metabolism. The dysfunction of intestinal barrier contributes to metabolic disorders. However, the role of intestinal PXR in metabolic diseases remains largely unknown. Here, we show that activation of PXR by tributyl citrate (TBC), an intestinal-selective PXR agonist, improves high fat diet (HFD)-induced obesity. The metabolic benefit of intestinal PXR activation is associated with upregulation of ß-1,3 galactosyltransferase 5 (B3galt5). Our results reveal that B3galt5 mainly expresses in the intestine and is a direct PXR transcriptional target. B3galt5 knockout exacerbates HFD-induced obesity, insulin resistance and inflammation. Mechanistically, B3galt5 is essential to maintain the integrity of intestinal mucus barrier. B3galt5 ablation impairs the O-glycosylation of mucin2, destabilizes the mucus layer, and increases intestinal permeability. Furthermore, B3galt5 deficiency abolishes the beneficial effect of intestinal PXR activation on metabolic disorders. Our results suggest the intestinal-selective PXR activation regulates B3galt5 expression and maintains metabolic homeostasis, making it a potential therapeutic strategy in obesity.

In vitro evaluation of flow diverter performance using a human fibrinogen-based flow model.

OBJECTIVE: Fibrin deposition represents a key step in aneurysm occlusion, promoting endothelization of implants and connective tissue organization as part of the aneurysm-healing mechanism. In this study, the authors introduce a novel in vitro testing platform for flow diverters based on human fibrinogen. METHODS: A flow diverter was deployed in 4 different glass models. The glass models had the same internal parent artery (4 mm) and aneurysm (8 mm) diameters with varying parent artery angulations (paraophthalmic, sidewall, bifurcation, and slightly curved models). The neck size and area were 4 mm and 25 mm2, respectively. Human fibrinogen (330 mg/dl) was circulated within the glass models at varying flow rates (0, 3, 4, and 5 ml/sec) with or without heparin, calcium chloride, and thrombin for as long as 6 hours or until complete fibrin coverage of the flow diverter's neck was achieved. Aneurysm neck coverage was defined as macroscopic fibrin deposition occluding the flow diverters' pores. Flow characteristics after flow diverter deployment were assessed with computational fluid dynamics analysis. The effects of flow rates, heparin, calcium chloride, and thrombin on fibrin deposition rates were tested using 1-way ANOVA and the Tukey test. RESULTS: A total of 84 replicates were performed. Human fibrin did not accumulate on the flow diverter stents under static conditions. The fibrin deposition rate on the aneurysm neck was significantly greater with the 5 ml/sec flow rate as compared to 3 ml/sec for all models. The paraophthalmic model had the highest inflow velocity of 48.7 cm/sec. The bifurcation model had the highest maximum shear stress (SS) and maximum normalized shear stress values at the device cells at 843.3 dyne/cm2 and 35.1 SS/SSinflow, respectively. The fibrin deposition rates of the paraophthalmic and bifurcation models were significantly higher than those of sidewall and slightly curved models for all additive or flow rate comparisons (p = 0.001 for all comparisons). The incorporation of thrombin significantly increased the fibrin deposition rates across all models (p = 0.001 for all models). CONCLUSIONS: Rates of fibrin deposition varied widely across different configurations and additive conditions in this novel in vitro model system. Fibrin accumulation started at the aneurysm inflow zone where flow velocity and shear stress were the highest. The primary factors influencing fibrin deposition included flow velocities, shear stress, and the addition of thrombin at a physiological concentration. Further research is needed to test the clinical utility of fibrinogen-based models for patient-specific aneurysms.

Clinical analysis of lupus miliaris disseminatus faciei: a cross-sectional study and literature review.

Background: The clinical similarity of lupus miliaris disseminatus faciei (LMDF) and other papular granulomatous facial disorders often makes its correct diagnosis challenging. Diagnosis often requires the assistance of pathological examination, and dermoscopy can be used as an auxiliary and non-invasive examination method, however, the current findings remain incomplete. Objectives: This study aimed to summarize the clinical, histopathological and dermoscopic features of LMDF in the Chinese Han population and aiming to provide practical significance to correct diagnosis. Methods: 109 patients of LMDF were collected in the Department of Dermatology, the Second Affiliated Hospital of Xi'an Jiaotong University from August 2015 to August 2023. The clinical and histopathological manifestations of all patients, as well as the dermoscopic image features of 44 cases, including background, follicular findings, vessels, and other structures, were summarized and evaluated. Results: The most significant histopathological features of LMDF in 109 cases is epithelioid granulomatous infiltrate in the superficial dermis, with or without caseation. The most significant dermoscopic features of LMDF in all 44 cases were orange structureless background (30/44), follicular plug (32/44), follicular white scar-like area (32/44), unspecific linear vessels (24/44), linear vessels with branch (24/44) and white streaks (18/44). Conclusion: Histopathologically, LMDF is characterized by the presence of epithelioid granulomatous infiltrate in the superficial dermis, with or without caseation. Dermoscopically, it exhibits a distinctive orange structureless background, follicular plug, follicular white scar-like area, nonspecific linear vessels, linear vessels with branches, and white streaks.

Luspatercept versus epoetin alfa in erythropoiesis-stimulating agent-naive, transfusion-dependent, lower-risk myelodysplastic syndromes (COMMANDS): primary analysis of a phase 3, open-label, randomised, controlled trial.

BACKGROUND: The preplanned interim analysis of the COMMANDS trial showed greater efficacy of luspatercept than epoetin alfa for treating anaemia in erythropoiesis-stimulating agent (ESA)-naive patients with transfusion-dependent, lower-risk myelodysplastic syndromes. In this Article, we report the results of the primary analysis of the trial. METHODS: COMMANDS is a phase 3, open-label, randomised, controlled trial conducted at 142 sites in 26 countries. Eligible patients were those aged 18 years or older, with myelodysplastic syndromes of very low risk, low risk, or intermediate risk (as defined by the Revised International Prognostic Scoring System), who were ESA-naive and transfusion dependent, and had a serum erythropoietin concentration of less than 500 U/L. Patients were stratified by baseline red blood cell transfusion burden, serum erythropoietin concentration, and ring sideroblast status, and randomly allocated (1:1) to receive luspatercept (1·0-1·75 mg/kg body weight, subcutaneously, once every 3 weeks) or epoetin alfa (450-1050 IU/kg body weight, subcutaneously, once a week; maximum total dose 80 000 IU) for at least 24 weeks. The primary endpoint was red blood cell transfusion independence lasting at least 12 weeks with a concurrent mean haemoglobin increase of at least 1·5 g/dL (weeks 1-24), evaluated in the intention-to-treat population. The safety population included all patients who received at least one dose of treatment. This trial is registered with ClinicalTrials.gov (NCT03682536; active, not recruiting). FINDINGS: Between Jan 2, 2019, and Sept 29, 2022, 363 patients were screened and randomly allocated: 182 (50%) to luspatercept and 181 (50%) to epoetin alfa. Median age was 74 years (IQR 69-80), 162 (45%) patients were female, and 201 (55%) were male. 289 (80%) were White, 44 (12%) were Asian, and two (1%) were Black or African American. 23 (6%) were Hispanic or Latino and 311 (86%) were not Hispanic or Latino. Median follow-up for the primary endpoint was 17·2 months (10·4-27·7) for the luspatercept group and 16·9 months (10·1-26·6) for the epoetin alfa group. A significantly greater proportion of patients in the luspatercept group reached the primary endpoint (110 [60%] vs 63 [35%]; common risk difference on response rate 25·4% [95% CI 15·8-35·0]; p<0·0001). Median follow-up for safety analyses was 21·4 months (IQR 14·2-32·4) for the luspatercept group and 20·3 months (12·7-30·9) for the epoetin alfa group. Common grade 3-4 treatment-emergent adverse events occurring among luspatercept recipients (n=182) were hypertension (19 [10%] patients), anaemia (18 [10%]), pneumonia (ten [5%]), syncope (ten [5%]), neutropenia (nine [5%]), thrombocytopenia (eight [4%]), dyspnoea (eight [4%]), and myelodysplastic syndromes (six [3%]); and among epoetin alfa recipients (n=179) were anaemia (14 [8%]), pneumonia (14 [8%]), neutropenia (11 [6%]), myelodysplastic syndromes (ten [6%]), hypertension (eight [4%]), iron overload (seven [4%]), and COVID-19 pneumonia (six [3%]). The most common serious treatment-emergent adverse events in both groups were pneumonia (nine [5%] luspatercept recipients and 13 [7%] epoetin alfa recipients) and COVID-19 (eight [4%] luspatercept recipients and ten [6%] epoetin alfa recipients). One death (due to acute myeloid leukaemia) considered to be luspatercept-related was reported at the interim analysis. INTERPRETATION: Luspatercept represents a new standard of care for ESA-naive patients with transfusion-dependent, lower-risk myelodysplastic syndromes. Significantly more patients had red blood cell transfusion independence and haematological improvement with luspatercept than with epoetin alfa, with benefits observed across patient subgroups. FUNDING: Celgene and Acceleron Pharma.

Whole genome resequencing reveals the adaptability of native chickens to drought, tropical and frigid environments in Xinjiang.

Chickens exhibit extensive genetic diversity and are distributed worldwide. Different chicken breeds have evolved to thrive in diverse environmental conditions. However, research on the genetic mechanisms underlying chicken adaptation to extreme environments, such as tropical, frigid and drought-prone regions, remains limited. In this study, we conducted whole-genome sequencing of 240 individuals from six native chicken breeds in Xinjiang, China, as well as 4 publicly available chicken breeds inhabiting regions with varying annual precipitations, temperatures, and altitudes. Our analysis revealed several genetic variants among the examined breeds. Furthermore, we investigated the genetic diversity and population structure of breeds residing in extreme drought and temperature environments by comparing them. Notably, native chicken breeds exhibited different genetic diversity and population structures. Moreover, we identified candidate genes associated with chicken adaptability to the environment, such as CORO2A, CTNNA3, AGMO, GRID2, BBOX1, COL3A1, INSR, SOX5, MAP2 and PLPPR1. Additionally, pathways such as lysosome, cysteine and methionine metabolism, glycosaminoglycan degradation, and Wnt signaling may be play crucial roles in regulating chicken adaptation to drought environments. Overall, these findings contribute to our understanding of the genetic mechanisms governing chicken adaptation to extreme environments, and also offer insights for enhancing the resilience of chicken breeds to different climatic conditions.

[Acupuncture combined with repeated transcranial magnetic stimulation for mild to moderate post-stroke depression: a randomized controlled trial].

OBJECTIVE: To explore the clinical effect of acupuncture combined with repeated transcranial magnetic stimulation (rTMS) for mild to moderate post-stroke depression. METHODS: Ninety patients with mild to moderate post-stroke depression were randomly divided into a combination group (30 cases, 4 cases dropped out), an acupuncture group (30 cases, 3 cases dropped out) and a rTMS group (30 cases, 5 cases dropped out). All the three groups received basic treatment, the combination group was treated with acupuncture combined with rTMS, the acupuncture group was treated with acupuncture, and the rTMS group was treated with rTMS. The acupuncture was applied at Baihui (GV 20), Yintang (GV 24+) , Danzhong (CV 17) and bilateral Shenmen (HT 7), Taichong (LR 3), Neiguan (PC 6). All the three groups were treated once a day, 5 times a week for 4 weeks. The Hamilton depression scale (HAMD-17) score, Pittsburgh sleep quality index (PSQI) score and event-related potential were compared among the three groups before and after treatment. RESULTS: After treatment, the HAMD-17 scores and PSQI scores in the three groups were reduced compared with those before treatment (P<0.01) , and the HAMD-17 score and PSQI score in the combination group were lower than those in the acupuncture group and the rTMS group (P<0.05). After treatment, the latency of event-related potential (P300, mismatch negativityï¼»MMNï¼½) in the three groups was shortened compared with that before treatment (P<0.05), and the latency of event-related potential in the combination group was shorter than that in the acupuncture group and the rTMS group (P<0.05). CONCLUSION: Acupuncture combined with rTMS can effectively alleviate the depressive state of patients with mild to moderate post-stroke depression, improve the sleep quality and the latency of event-related potential P300 and MMN.

Artificial intelligence system for outcome evaluations of human in vitro fertilization-derived embryos.

BACKGROUND: In vitro fertilization (IVF) has emerged as a transformative solution for infertility. However, achieving favorable live-birth outcomes remains challenging. Current clinical IVF practices in IVF involve the collection of heterogeneous embryo data through diverse methods, including static images and temporal videos. However, traditional embryo selection methods, primarily reliant on visual inspection of morphology, exhibit variability and are contingent on the experience of practitioners. Therefore, an automated system that can evaluate heterogeneous embryo data to predict the final outcomes of live births is highly desirable. METHODS: We employed artificial intelligence (AI) for embryo morphological grading, blastocyst embryo selection, aneuploidy prediction, and final live-birth outcome prediction. We developed and validated the AI models using multitask learning for embryo morphological assessment, including pronucleus type on day 1 and the number of blastomeres, asymmetry, and fragmentation of blastomeres on day 3, using 19,201 embryo photographs from 8271 patients. A neural network was trained on embryo and clinical metadata to identify good-quality embryos for implantation on days or day 5, and predict live-birth outcomes. Additionally, a 3D convolutional neural network was trained on 418 time-lapse videos of preimplantation genetic testing (PGT)-based ploidy outcomes for aneuploidy prediction and consequent live-birth outcomes. RESULTS: These two approaches enabled us to automatically assess the implantation potential. By combining embryo and maternal metrics in an ensemble AI model, we evaluated live-birth outcomes in a prospective cohort that achieved higher accuracy than experienced embryologists (46.1% vs. 30.7% on day 3, 55.0% vs. 40.7% on day 5). Our results demonstrate the potential for AI-based selection of embryos based on characteristics beyond the observational abilities of human clinicians (area under the curve: 0.769, 95% confidence interval: 0.709-0.820). These findings could potentially provide a noninvasive, high-throughput, and low-cost screening tool to facilitate embryo selection and achieve better outcomes. CONCLUSIONS: Our study underscores the AI model's ability to provide interpretable evidence for clinicians in assisted reproduction, highlighting its potential as a noninvasive, efficient, and cost-effective tool for improved embryo selection and enhanced IVF outcomes. The convergence of cutting-edge technology and reproductive medicine has opened new avenues for addressing infertility challenges and optimizing IVF success rates.

Bioinformatic analysis indicated that STARD4-AS1 might be a novel ferroptosis-related biomarker of oral squamous cell carcinoma.

Background: Oral squamous cell carcinoma (OSCC) stands as the predominant form of oral cancer, marked by a poor prognosis. Ferroptosis, a type of programmed cell death, plays a critical role in the initiation and progression of various cancers. Long non-coding RNAs (lncRNAs) are prominent in modulating cancer development. Nevertheless, the prognostic significance of ferroptosis-related lncRNAs (FRLs) in OSCC remains inadequately explored. This study aims to develop a predictive signature based on FRLs to forecast the prognosis of OSCC patients. Methods: We gathered expression profiles of FRLs along with clinical data from The Cancer Genome Atlas (TCGA) and FerrDb databases. A prognostic model based on 10 FRLs were constructed using Cox regression analyses with LASSO algorithms, and their predictive power was evaluated. Then, the model was used to investigate functional enrichment, immune landscape, m6A genes, somatic variations, and drug response in different risk cohorts of patients. Finally, the expression and function of STARD4-AS1 (steroidogenic acute regulator protein-related lipid transfer domain containing 4-antisense RNA 1), a potential prognostic marker for OSCC screening based on our bioinformatics analysis, were investigated in vitro. Results: We developed a signature comprising 10 FRLs to stratify patients into two risk cohorts according to their calculated risk scores. Patients classified as high-risk exhibited significantly poorer prognoses compared to those in the low-risk cohort. Furthermore, survival analysis, patient risk heat plot, and risk curve verified the accuracy of the signature. The role of this signature in OSCC was well investigated using immune microenvironment, mutational, and gene set enrichment analysis (GSEA). Moreover, seven drugs, including cisplatin and docetaxel, were identified as potential treatments for patients with high-risk cancers. In addition, the knockdown of STARD4-AS1 in OSCC cell lines markedly inhibited cell proliferation and migration and induced ferroptosis. Conclusion: Using this signature may improve overall survival predictions in OSCC, throwing new light on immunotherapies and targeted therapies. Moreover, STARD4-AS1 might regulate the process of ferroptosis and could be used as a novel biomarker of OSCC.

State-specific Regulation of Electrical Stimulation in the Intralaminar Thalamus of Macaque Monkeys: Network and Transcriptional Insights into Arousal.

Long-range thalamocortical communication is central to anesthesia-induced loss of consciousness and its reversal. However, isolating the specific neural networks connecting thalamic nuclei with various cortical regions for state-specific anesthesia regulation is challenging, with the biological underpinnings still largely unknown. Here, simultaneous electroencephalogram-fuctional magnetic resonance imaging (EEG-fMRI) and deep brain stimulation are applied to the intralaminar thalamus in macaques under finely-tuned propofol anesthesia. This approach led to the identification of an intralaminar-driven network responsible for rapid arousal during slow-wave oscillations. A network-based RNA-sequencing analysis is conducted of region-, layer-, and cell-specific gene expression data from independent transcriptomic atlases and identifies 2489 genes preferentially expressed within this arousal network, notably enriched in potassium channels and excitatory, parvalbumin-expressing neurons, and oligodendrocytes. Comparison with human RNA-sequencing data highlights conserved molecular and cellular architectures that enable the matching of homologous genes, protein interactions, and cell types across primates, providing novel insight into network-focused transcriptional signatures of arousal.

The First Identification of Homomorphic XY Sex Chromosomes by Integrating Cytogenetic and Transcriptomic Approaches in Plestiodon elegans (Scincidae).

The sex chromosomes of skinks are usually poorly differentiated and hardly distinguished by cytogenetic methods. Therefore, identifying sex chromosomes in species lacking easily recognizable heteromorphic sex chromosomes is necessary to fully understand sex chromosome diversity. In this paper, we employed cytogenetics, sex quantification of genes, and transcriptomic approaches to characterize the sex chromosomes in Plestiodon elegans. Cytogenetic examination of metaphases revealed a diploid number of 2n = 26, consisting of 12 macrochromosomes and 14 microchromosomes, with no significant heteromorphic chromosome pairs, speculating that the sex chromosomes may be homomorphic or poorly differentiated. The results of the sex quantification of genes showed that Calumenin (calu), COPI coat complex subunit γ 2 (copg2), and Smoothened (smo) were at half the dose in males as in females, suggesting that they are on the X chromosome. Transcriptomic data analysis from the gonads yielded the excess expression male-specific genes (n = 16), in which five PCR molecular markers were developed. Restricting the observed heterozygosity to males suggests the presence of homomorphic sex chromosomes in P. elegans, XX/XY. This is the first breakthrough in the study of the sex chromosomes of Plestiodon.

Photoelectrochemical immunoassay of cardiac troponin I based on ZnTCPP/CdIn2S4 type-II heterojunction and co-catalyzed precipitation biolabeling.

CdIn2S4 and zinc tetrakis(4-carboxyphenyl)porphyrin (ZnTCPP) were synthesized by hydrothermal method, and an organic dye-sensitized inorganic semiconductor ZnTCPP/CdIn2S4 type II heterojunction was constructed on a fluorine-doped tin oxide (FTO) substrate electrode. A sandwich immunostructure for signal-attenuation photoelectrochemical (PEC) detection of cardiac troponin I (cTnI) was constructed using the ZnTCPP/CdIn2S4/FTO photoanode and a horseradish peroxidase (HRP)-ZnFe2O4-Ab2-bovine serum albumin (BSA) immunolabeling complex. The bioenzyme HRP and the HRP-like nanozyme ZnFe2O4 can co-catalyze the oxidation of 4-chloro-1-naphthol (4-CN) by H2O2 to produce an insoluble precipitate on the photoanode, thus notably reducing the anodic photocurrent for quantitative determination of cTnI. Under the optimal conditions, the photocurrent at 0 V vs. SCE in 0.1 M phosphate buffer solution (pH 7.40) containing 0.1 M ascorbic acid was linear with the logarithm of cTnI concentration from 500 fg mL-1 to 50.0 ng mL-1, and the limit of detection (LOD, S/N = 3) is 0.15 pg mL-1. Spiked recoveries were 95.1% ~ 104% for assay of cTnI in human serum samples.

METTL14 inhibits the malignant processes of gastric cancer cells by promoting N6-methyladenosine (m6A) methylation of TAF10.

N6-methyladenosine (m6A) methylation mediates cancer development by regulating cell proliferation and metastasis. This study aimed to identify whether methyltransferase 14 (METTL14) affects gastric cancer (GC) cellular functions and its underlying mechanism. METTL14 and TATA-box binding protein associated factor 10 (TAF10) levels were examined using quantitative real-time PCR, immunohistochemical assay, and Western blot. Biological functions were assessed using cell counting kit-8, colony formation, and transwell assays. The interaction between METTL14 and TAF10 was analyzed using RNA immunoprecipitation, methylated RNA immunoprecipitation, and luciferase reporter assay. A xenograft tumor mouse model was established to assess the role of METTL14 in vivo. The results suggested that METTL14 was low expressed and TAF10 was highly expressed in GC tissues and cells. METTL14 overexpression inhibited GC cell viability, colony, migration, and invasion. TAF10 was predicted and confirmed to be negatively related to METTL14. METTL14 promoted m6A methylation of TAF10 and inhibited TAF10 stability. Moreover, TAF10 counteracted the cellular behaviors regulated by METTL14. Overexpression of METTL14 inhibited tumor growth and histopathology. In conclusion, METTL14 inhibits GC progression by attenuating GC cell proliferation, migration, and invasion. Mechanistically, METTL14 promoted m6A methylation of TAF10, suppressed the stability of TAF10, and thus downregulated the TAF10 levels, These results provide a new insight into GC therapy.

Cyclic Aspiration in Mechanical Thrombectomy: Influencing Factors and Experimental Validation.

BACKGROUND AND PURPOSE: Mechanical thrombectomy is a fundamental intervention for acute ischemic stroke treatment. While conventional techniques are effective, cyclic aspiration (CyA) shows potential for better recanalization rates. We aim to investigate factors affecting CyA and compare them with static aspiration (StA). MATERIALS AND METHODS: StA setup consisted of an aspiration pump connected to pressure transducer. CyA was tested with five subsequent iterations: single solenoid valve with air+saline (1) or saline alone (2) as aspiration medium; two solenoid valves with air+saline (3) as aspiration medium; complete air removal and saline feeding (4); pressurized saline feeding (5). To assess the efficacy of clot ingestion, the pressure transducer was replaced with a distal aspiration catheter. Moderately stiff clot analogs (15 mm) were used to investigate the ingestion quantified as clot relative weight loss. Additionally, the aspiration flow rate was assessed for each setup. RESULTS: With CyA setup 1, the amplitude of the achieved negative pressure waves declined with increasing frequencies but progressively increased with each subsequent iteration, achieving a maximum amplitude of 81 kPa for setup 5 at 1Hz. Relative clot weight loss was significantly higher with setup 5 at 5Hz than with StA (100% vs. 37,8%; p=0.05). Aspiration flow rate was lower with CyA than with StA (setup 5 at 5Hz: 199,8ml/min vs. StA: 311ml/min; p<0.01). CONCLUSIONS: Cyclic aspiration with the appropriate setup may represent an encouraging innovation in mechanical thrombectomy, offering a promising pathway for improving efficacy in clot ingestion and recanalization. The observed benefits warrant confirmation in a clinical setting. ABBREVIATIONS: CyA -cyclic aspiration, StA - static aspiration, FPR -first pass reperfusion, MT -mechanical thrombectomy, DAC -distal aspiration catheter, LVO -large vessel occlusion.

Age-related differences in drug-induced liver injury: a retrospective single-center study from a large liver disease specialty hospital in China, 2002-2022.

BACKGROUND AND AIMS: Drug-induced liver injury (DILI) is a prevalent adverse reaction in clinical settings. However, there is limited research on age-related differences in DILI. We performed a large-scale retrospective study to delineate the characteristics of DILI across different age groups. METHODS: We collected data on a total of 17,946 patients with confirmed DILI hospitalized at the Fifth Medical Center of the People's Liberation Army (PLA) General Hospital in Beijing, China, from January 1, 2002, to December 31, 2022. The patients were stratified based on age into the following groups: children (< 18 years), young adults (18-44 years), middle-aged individuals (45-64 years), and elderly individuals (≥ 65 years). We gathered demographic information, medical histories, laboratory results, disease severity assessments, and mortality statistics for all patients. RESULTS: Overall, the distribution of DILI cases across different age groups was as follows: 6.57% were children, 24.82% were young adults, 49.06% were middle-aged individuals, and 19.54% were elderly individuals. The percentage of females increased with age, rising from 36.47% in the pediatric group to 60.51% in the elderly group. Notably, central nervous system agents (15.44%) and anti-infectious agents (21.80%) were more commonly associated with DILI in children, while cardiovascular agents (10.58%) and herbal dietary supplements or traditional medicines (H/TMs) (26.29%) were more prevalent among elderly people with DILI. Among all age groups, hepatocellular-type DILI was more common in the pediatric group (p < 0.001), whereas cholestatic-type DILI and chronic DILI were more prevalent in the elderly group (p < 0.001). Acute liver failure (ALF) and fatal outcomes were more prevalent in the pediatric and elderly groups, particularly in the pediatric group (2.04%, p = 0.041; 0.85%, p = 0.007, respectively). CONCLUSIONS: Children and elderly individuals face a higher risk of adverse outcomes following DILI.

Acquisition Efficiency and Technical Repeatability of Dual-Frequency 3D Vector MR Elastography of the Liver.

BACKGROUND: MR elastography (MRE) at 60 Hz is widely used for staging liver fibrosis. MRE with lower frequencies may provide inflammation biomarkers. PURPOSE: To establish a practical simultaneous dual-frequency liver MRE protocol at both 30 Hz and 60 Hz during a single examination and validate the occurrence of second harmonic waves at 30 Hz. STUDY TYPE: Retrospective. SUBJECTS: One hundred six patients (48 females, age: 50.0 ± 13.4 years) were divided as follows: Cohort One (15 patients with chronic liver disease [CLD] and 25 healthy volunteers) with simultaneous dual-frequency MRE. Cohort Two (66 patients with CLD) with second harmonic MRE. FIELD STRENGTH/SEQUENCE: 3-T, single- or dual-frequency MRE at 30 Hz and 60 Hz. ASSESSMENT: Liver stiffness (LS) in both cohorts was evaluated with manually placed volumetric ROIs by two independent analyzers. Image quality was assessed by three independent readers on a 4-point scale (0-3: none/failed, fair, moderate, excellent) based on the depth of wave propagation with 1/3 incremental penetration. The success rate was derived from the percentage of nonzero quality scores. STATISTICAL TESTS: Measurement agreement, bias, and repeatability of LS were assessed using intraclass correlation coefficients (ICCs), Bland-Altman plots, and repeatability coefficient (RC). Mann-Whitney U tests were used to evaluate the differences in image quality between different methods. A P-value <0.05 was considered statistically significant. RESULTS: Success rate was 97.5% in Cohort One and 91% success rate for the second harmonic MRE in Cohort Two. The second harmonic and conventional MRE showed excellent agreement in LS (all ICCs >0.90). The quality scores for the second harmonic wave images were lower than those from the conventional MRE (Z = -4.523). DATA CONCLUSION: Compared with conventional and second harmonic methods, simultaneous dual-frequency had better image quality, high success rate and the advantage of intrinsic co-registration, while the second harmonic method can be an alternative if custom waveform is not available. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 1.

High-Entropy Engineering Reinforced Surface Electronic States and Structural Defects of Hierarchical Metal Oxides@Graphene Fibers toward High-Performance Wearable Supercapacitors.

Construction advanced fibers with high Faradic activity and conductivity are effective to realize high energy density with sufficient redox reactions for fiber-based electrochemical supercapacitors (FESCs), yet it is generally at the sacrifice of kinetics and structural stability. Here, a high-entropy doping strategy is proposed to develop high-energy-density FESCs based on high-entropy doped metal oxide@graphene fiber composite (HE-MO@GF). Due to the synergistic participation of multi-metal elements via high-entropy doping, the HE-MO@GF features abundant oxygen vacancies from introducing various low-valence metal ions, lattice distortions, and optimized electronic structure. Consequently, the HE-MO@GF maintains sufficient active sites, a low diffusion barrier, fast adsorption kinetics, improved electronic conductivity, enhanced structural stability, and Faradaic reversibility. Thereinto, HE-MO@GF presents ultra-large areal capacitance (3673.74 mF cm-2) and excellent rate performance (1446.78 mF cm-2 at 30 mA cm-2) in 6 M KOH electrolyte. The HE-MO@GF-based solid-state FESCs also deliver high energy density (132.85 µWh cm-2), good cycle performance (81.05% of capacity retention after 10,000 cycles), and robust tolerance to sweat erosion and multiple washing, which is woven into the textile to power various wearable devices (e.g., watch, badge and luminous glasses). This high-entropy strategy provides significant guidance for designing innovative fiber materials and highlights the development of next-generation wearable energy devices.