METTL1-mediated tRNA m7G methylation and translational dysfunction restricts breast cancer tumorigenesis by fueling cell cycle blockade.

BACKGROUND: RNA modifications of transfer RNAs (tRNAs) are critical for tRNA function. Growing evidence has revealed that tRNA modifications are related to various disease processes, including malignant tumors. However, the biological functions of methyltransferase-like 1 (METTL1)-regulated m7G tRNA modifications in breast cancer (BC) remain largely obscure. METHODS: The biological role of METTL1 in BC progression were examined by cellular loss- and gain-of-function tests and xenograft models both in vitro and in vivo. To investigate the change of m7G tRNA modification and mRNA translation efficiency in BC, m7G-methylated tRNA immunoprecipitation sequencing (m7G tRNA MeRIP-seq), Ribosome profiling sequencing (Ribo-seq), and polysome-associated mRNA sequencing were performed. Rescue assays were conducted to decipher the underlying molecular mechanisms. RESULTS: The tRNA m7G methyltransferase complex components METTL1 and WD repeat domain 4 (WDR4) were down-regulated in BC tissues at both the mRNA and protein levels. Functionally, METTL1 inhibited BC cell proliferation, and cell cycle progression, relying on its enzymatic activity. Mechanistically, METTL1 increased m7G levels of 19 tRNAs to modulate the translation of growth arrest and DNA damage 45 alpha (GADD45A) and retinoblastoma protein 1 (RB1) in a codon-dependent manner associated with m7G. Furthermore, in vivo experiments showed that overexpression of METTL1 enhanced the anti-tumor effectiveness of abemaciclib, a cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor. CONCLUSION: Our study uncovered the crucial tumor-suppressive role of METTL1-mediated tRNA m7G modification in BC by promoting the translation of GADD45A and RB1 mRNAs, selectively blocking the G2/M phase of the cell cycle. These findings also provided a promising strategy for improving the therapeutic benefits of CDK4/6 inhibitors in the treatment of BC patients.

Haplotype-resolved T2T reference genomes for wild and domesticated accessions shed new insights into the domestication of jujube.

Chinese jujube (Ziziphus jujuba Mill.) is one of the most important deciduous tree fruits in China, with substantial economic and nutritional value. Jujube was domesticated from its wild progenitor, wild jujube (Z. jujuba var. spinosa), and both have high medicinal value. Here we report the 767.81- and 759.24-Mb haplotype-resolved assemblies of a dry-eating 'Junzao' jujube (JZ) and a wild jujube accession (SZ), using a combination of multiple sequencing strategies. Each assembly yielded two complete haplotype-resolved genomes at the telomere-to-telomere (T2T) level, and ~81.60 and 69.07 Mb of structural variations were found between the two haplotypes within JZ and SZ, respectively. Comparative genomic analysis revealed a large inversion on each of chromosomes 3 and 4 between JZ and SZ, and numerous genes were affected by structural variations, some of which were associated with starch and sucrose metabolism. A large-scale population analysis of 672 accessions revealed that wild jujube originated from the lower reaches of the Yellow River and was initially domesticated at local sites. It spread widely and was then independently domesticated at the Shanxi-Shaanxi Gorge of the middle Yellow River. In addition, we identified some new selection signals regions on genomes, which are involved in the tissue development, pollination, and other aspects of jujube tree morphology and fertilization domestication. In conclusion, our study provides high-quality reference genomes of jujube and wild jujube and new insights into the domestication history of jujube.

Simultaneous and ultrafast detection of pan-SARS-coronaviruses and influenza A/B viruses by a novel multiplex real-time RT-PCR assay.

Here we report an ultrafast quadruplex RT-qPCR assay with robust diagnostic ability to detect and distinguish pan-SARS-CoVs and influenza A/B viruses within 35 min. This quadruplex RT-qPCR assay comprised of one novel RNA-based internal control targeting human ß2-microglobulin (B2M) for process accuracy and three newly-designed primers-probe sets targeting the envelope protein (E) of pan-SARS-CoV, matrix protein (MP) of influenza A virus and non-structural (NS) region of influenza B virus. This quadruplex assay exhibited a sensitivity comparable to its singleplex counterparts and a slightly higher to that of the Centers for Disease Control and Prevention-recommended SARS-CoV-2 and influenza A/B assays. The novel assay showed no false-positive amplifications with other common respiratory viruses, and its 95 % limits of detection for pan-SARS-CoV and influenza A/B virus was 4.26-4.52 copies/reaction. Moreover, the assay was reproducible with less than 1 % coefficient of variation and adaptable testing different clinical and environmental samples. Our ultrafast quadruplex RT-qPCR assay can serve as an attractive tool for effective differentiation of influenza A/B virus and SARS-CoV-2, but more importantly prognose the reemergence/emergence of SARS and novel coronaviruses or influenza viruses from animal spillover.

A Fully Metaoptical Zoom Lens with a Wide Range.

Metalenses are typically designed for a fixed focal length, restricting their functionality to static scenarios. Various methods have been introduced to achieve the zoom function in metalenses. These methods, however, have a very limited zoom range, or they require additional lenses to achieve direct imaging. Here, we demonstrate a zoom metalens based on axial movement that performs both the imaging and the zoom function. The key innovation is the use of a polynomial phase profile that mimics an aspheric lens, which allows an extended depth of focus, enabling a large zoom range. Experimental results show that this focal length variation, combined with the extended depth of focus, translates into an impressive zoom range of 11.9× while maintaining good imaging quality. We see applications for such a zoom metalens in surveillance cameras of drones or microrobots to reduce their weight and volume, thus enabling more flexible application scenarios.

Reward Circuit Local Field Potential Modulations Precede Risk Taking.

Risk taking behavior is a symptom of multiple neuropsychiatric disorders and often lacks effective treatments. Reward circuitry regions including the amygdala, orbitofrontal cortex, insula, and anterior cingulate have been implicated in risk-taking by neuroimaging studies. Electrophysiological activity associated with risk taking in these regions is not well understood in humans. Further characterizing the neural signalling that underlies risk-taking may provide therapeutic insight into disorders associated with risk-taking. Eleven patients with pharmacoresistant epilepsy who underwent stereotactic electroencephalography with electrodes in the amygdala, orbitofrontal cortex, insula, and/or anterior cingulate participated. Patients participated in a gambling task where they wagered on a visible playing card being higher than a hidden card, betting $5 or $20 on this outcome, while local field potentials were recorded from implanted electrodes. We used cluster-based permutation testing to identify reward prediction error signals by comparing oscillatory power following unexpected and expected rewards. We also used cluster-based permutation testing to compare power preceding high and low bets in high-risk (<50% chance of winning) trials and two-way ANOVA with bet and risk level to identify signals associated with risky, risk averse, and optimized decisions. We used linear mixed effects models to evaluate the relationship between reward prediction error and risky decision signals across trials, and a linear regression model for associations between risky decision signal power and Barratt Impulsiveness Scale scores for each patient. Reward prediction error signals were identified in the amygdala (p=0.0066), anterior cingulate (p=0.0092), and orbitofrontal cortex (p=6.0E-4, p=4.0E-4). Risky decisions were predicted by increased oscillatory power in high-gamma frequency range during card presentation in the orbitofrontal cortex (p=0.0022), and by increased power following bet cue presentation across the theta-to-beta range in the orbitofrontal cortex ( p =0.0022), high-gamma in the anterior cingulate ( p =0.0004), and high-gamma in the insula ( p =0.0014). Risk averse decisions were predicted by decreased orbitofrontal cortex gamma power ( p =2.0E-4). Optimized decisions that maximized earnings were preceded by decreases within the theta to beta range in orbitofrontal cortex ( p =2.0E-4), broad frequencies in amygdala ( p =2.0E-4), and theta to low-gamma in insula ( p =4.0E-4). Insula risky decision power was associated with orbitofrontal cortex high-gamma reward prediction error signal ( p =0.0048) and with patient impulsivity ( p =0.00478). Our findings identify and help characterize reward circuitry activity predictive of risk-taking in humans. These findings may serve as potential biomarkers to inform the development of novel treatment strategies such as closed loop neuromodulation for disorders of risk taking.

Rectifying METTL4-Mediated N6-Methyladenine Excess in Mitochondrial DNA Alleviates Heart Failure.

BACKGROUND: Myocardial mitochondrial dysfunction underpins the pathogenesis of heart failure (HF), yet therapeutic options to restore myocardial mitochondrial function are scarce. Epigenetic modifications of mitochondrial DNA (mtDNA), such as methylation, play a pivotal role in modulating mitochondrial homeostasis. However, their involvement in HF remains unclear. METHODS: Experimental HF models were established through continuous angiotensin II and phenylephrine (AngII/PE) infusion or prolonged myocardial ischemia/reperfusion injury. The landscape of N6-methyladenine (6mA) methylation within failing cardiomyocyte mtDNA was characterized using high-resolution mass spectrometry and methylated DNA immunoprecipitation sequencing. A tamoxifen-inducible cardiomyocyte-specific Mettl4 knockout mouse model and adeno-associated virus vectors designed for cardiomyocyte-targeted manipulation of METTL4 (methyltransferase-like protein 4) expression were used to ascertain the role of mtDNA 6mA and its methyltransferase METTL4 in HF. RESULTS: METTL4 was predominantly localized within adult cardiomyocyte mitochondria. 6mA modifications were significantly more abundant in mtDNA than in nuclear DNA. Postnatal cardiomyocyte maturation presented with a reduction in 6mA levels within mtDNA, coinciding with a decrease in METTL4 expression. However, an increase in both mtDNA 6mA level and METTL4 expression was observed in failing adult cardiomyocytes, suggesting a shift toward a neonatal-like state. METTL4 preferentially targeted mtDNA promoter regions, which resulted in interference with transcription initiation complex assembly, mtDNA transcriptional stalling, and ultimately mitochondrial dysfunction. Amplifying cardiomyocyte mtDNA 6mA through METTL4 overexpression led to spontaneous mitochondrial dysfunction and HF phenotypes. The transcription factor p53 was identified as a direct regulator of METTL4 transcription in response to HF-provoking stress, thereby revealing a stress-responsive mechanism that controls METTL4 expression and mtDNA 6mA. Cardiomyocyte-specific deletion of the Mettl4 gene eliminated mtDNA 6mA excess, preserved mitochondrial function, and mitigated the development of HF upon continuous infusion of AngII/PE. In addition, specific silencing of METTL4 in cardiomyocytes restored mitochondrial function and offered therapeutic relief in mice with preexisting HF, irrespective of whether the condition was induced by AngII/PE infusion or myocardial ischemia/reperfusion injury. CONCLUSIONS: Our findings identify a pivotal role of cardiomyocyte mtDNA 6mA and the corresponding methyltransferase, METTL4, in the pathogenesis of mitochondrial dysfunction and HF. Targeted suppression of METTL4 to rectify mtDNA 6mA excess emerges as a promising strategy for developing mitochondria-focused HF interventions.

Long term outcome after endovascular treatment for large ischemic core acute stroke is associated with hypoperfusion intensity ratio and onset-to-reperfusion time.

BACKGROUND: Endovascular treatment (EVT) is effective for large vessel occlusion (LVO) stroke with smaller volumes of CT perfusion (CTP)-defined core. However, the influence of perfusion imaging during thrombectomy on the functional outcomes of patients with large ischemic core (LIC) stroke at both early and late time windows is uncertain in real-world practice. METHOD: A retrospective analysis was performed on 99 patients who underwent computed tomography angiography (CTA) and CT perfusion (CTP)-Rapid Processing of Perfusion and Diffusion (RAPID) before EVT and had a baseline ischemic core ≥ 50 mL and/or Alberta Stroke Program Early CT Score (ASPECTS) score of 0-5. The primary outcome was the three-month modified Rankin Scale (mRS) score. Data were analyzed by binary logistic regression and receiver operating characteristic (ROC) curves. RESULTS: A fair outcome (mRS, 0-3) was found in 34 of the 99 patients while 65 had a poor prognosis (mRS, 4-6). The multivariate logistic regression analysis showed that onset-to-reperfusion (OTR) time (odds ratio [OR], 1.004; 95% confidence interval [CI], 1.001-1.007; p = 0.008), ischemic core (OR, 1.066; 95% CI, 1.024-1.111; p = 0.008), and the hypoperfusion intensity ratio (HIR) (OR, 70.898; 95% CI, 1.130-4450.152; p = 0.044) were independent predictors of outcome. The combined results of ischemic core, HIR, and OTR time showed good performance with an area under the ROC curve (AUC) of 0.937, significantly higher than the individual variables (p < 0.05) using DeLong's test. CONCLUSIONS: Higher HIR and longer OTR time in large core stroke patients were independently associated with unfavorable three-month outcomes after EVT.

Nonreciprocal P T-symmetric magnon laser in spinning cavity optomagnonics.

We propose a scheme to achieve nonreciprocal parity-time (P T)-symmetric magnon laser in a P T-symmetric cavity optomagnonical system. The system consists of active and passive optical spinning resonators. We demonstrate that the Fizeau light-dragging effect induced by the spinning of a resonator results in significant variations in magnon gain and stimulated emitted magnon numbers for different driving directions. We find that utilizing the Fizeau light-dragging effect allows the system to operate at ultra-low thresholds even without reaching gain-loss balance. A one-way magnon laser can also be realized across a range of parameters. High tunability of the magnon laser is achieved by changing the spinning speed of the resonators and driving direction. Our work provides a new way to explore various nonreciprocal effects in non-Hermitian magnonic systems, which may be applied to manipulate photons and magnons in multi-body non-Hermitian coupled systems.

Assessment of sleep disturbance in patients with Wilson's disease.

BACKGROUND: Wilson's disease (WD) is frequently manifested with anxiety, depression and sleep disturbance; this investigation aimed to elucidate these manifestations and identify the influencing factors of sleep disturbance. METHODS: Sleep disturbance, anxiety and depression were compared in 42 WD and 40 age- and gender-matched healthy individuals. 27 individuals indicated a neurological form of the disease (NV), and 15 had a non-neurological variant (NNV). RESULTS: This investigation revealed that the Parkinson's disease sleep scale (PDSS) score of WD individuals was lower, whereas their Epworth Sleepiness Scale (ESS), Pittsburgh sleep quality index (PSQI), Hamilton Anxiety Scale (HAMA), and Hamilton Depression Scale (HAMD) scores were higher than the healthy individuals (p < 0.05). Furthermore, the WD subjects had markedly increased prevalence of poor sleep quality, anxiety, and depression than healthy individuals (p < 0.05). Subgroup analysis showed that NV subjects had significantly higher scores on the UWDRS, PSQI, HAMA, and HAMD scales than those in the NV group, as well as higher rates of EDS, anxiety, and depression (p < 0.05). In patients with sleep disturbance, we identified UWDRS, neurological variant, and depression as associated factors. The linear regression model demonstrated depression as the dominant risk factor. CONCLUSIONS: Depression is highly correlated with and is a determinant of sleep disturbance in WD patients.

Proteome-wide identification and functional analysis of ubiquitinated proteins in Hepa1-6 cells by knockdown of E3 ubiquitin ligase SIAH1.

Background: Hepatocellular carcinoma (HCC) is an aggressive malignancy that poses a serious threat to human life. The conventional therapies for HCC cannot substantially improve overall survival (OS), disease duration, and prognosis. Therefore, it is important to study the underlying mechanism of HCC and seek better methods for HCC prevention and treatment. Ubiquitination is a post-translational modification that modulates great cellular function by cooperating with E1, E2, and E3 ligases. Yet, the ubiquitination and lysine residues in HCC are still elusive. Seven in absentia homolog 1 (SIAH1), as an important E3 ubiquitin ligase, regulates ubiquitin-mediated proteolysis to function as a tumor suppressor in HCC. In the present study, we downregulated SIAH1 in the mouse HCC cell line Hepa1-6 and studied its function by using proteome-wide identification. Methods: SIAH1 was knocked down by SIAH1 short hairpin RNA (shRNA) in mouse HCC cell line Hepa1-6 cells, and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis was conducted to analyze the ubiquitinated proteins. Functional analysis was performed using Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment. Results: The systematic profiling showed a total of 550 differently expressed proteins (DEPs), including 263 upregulated DEPs and 287 downregulated DEPs. Considering the amino acid sequences around the modified lysine residues, seven proteins were identified as conserved ubiquitination motifs in the peptides. The ubiquitinated proteins were mainly distributed in the cytoplasm, nucleus, and plasma membrane. Functional analysis suggested that the ubiquitinated proteins were mostly enriched in the nucleus, cytoplasm, and extracellular space; in addition, the ubiquitinated proteins were mostly attributed to the protein binding, and disease. The ubiquitinated proteins modulate HCC by mapping lysine modification sites. Conclusions: The use of high-throughput characterization to identify novel and specific targets associated with SIAH1 is of great significance in terms of functional weight. The results obtained in this paper from the analysis of proteomic data provided novel insights into ubiquitination regulation in HCC, which pave the way for further research and mechanism discovery of HCC.

Brain-wide human oscillatory local field potential activity during visual working memory.

Oscillatory activity in the local field potential (LFP) is thought to be a marker of cognitive processes. To understand how it differentiates tasks and brain areas in humans, we recorded LFPs in 15 adults with intracranial depth electrodes, as they performed visual-spatial and shape working memory tasks. Stimulus appearance produced widespread, broad-band activation, including in occipital, parietal, temporal, insular, and prefrontal cortex, and the amygdala and hippocampus. Occipital cortex was characterized by most elevated power in the high-gamma (100-150 Hz) range during the visual stimulus presentation. The most consistent feature of the delay period was a systematic pattern of modulation in the beta frequency (16-40 Hz), which included a decrease in power of variable timing across areas, and rebound during the delay period. These results reveal the widespread nature of oscillatory activity across a broad brain network and region-specific signatures of oscillatory processes associated with visual working memory.

Clinical significance of ribosome production factor 2 homolog in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide. Dysregulation of ribosome biogenesis increases the risk of cancer. RPF2 (ribosome production factor 2 homolog), a member of the BRIX family, is involved in ribosome biogenesis. However, the biological functions of RPF2 in HCC remain unclear. This study aims to evaluate the function of RPF2 and its clinical significance in HCC. We collected 45 pairs of HCC/adjacent samples and 291 HCC samples. These samples were used to perform immunohistochemical analysis and western blot. Six cell lines were used to perform western blot, and two of cell lines, SMCC-7721 and SNU449, were subjected to CCK-8, wound healing and transwell assays. Immunofluorescence staining was executed in SMCC-7721 cells. The protein levels of RPF2 were higher in HCC tissues than in adjacent tissues. Immunofluorescence staining showed that the RPF2 protein was located in the nucleuses, especially the nucleolus. Furthermore, the immunohistochemical analysis showed that high expression levels of nuclear RPF2 correlated with poor prognosis, vascular invasion, liver cirrhosis and tumor size. Cell experiments showed that overexpression of RPF2 promoted cell proliferation, migration and invasion, while knockdown of RPF2 tended to show the opposite effect. This is the first report that RPF2 is involved in HCC progression. The levels of RPF2 were significantly high in HCC tumors and had a side effect on prognosis in HCC patients. RPF2 has the potential to be a useful marker for HCC.

Metformin rejuvenates Nap1l2-impaired immunomodulation of bone marrow mesenchymal stem cells via metabolic reprogramming.

Ageing and cell senescence of mesenchymal stem cells (MSCs) limited their immunomodulation properties and therapeutic application. We previously reported that nucleosome assembly protein 1-like 2 (Nap1l2) contributes to MSCs senescence and osteogenic differentiation. Here, we sought to evaluate whether Nap1l2 impairs the immunomodulatory properties of MSCs and find a way to rescue the deficient properties. We demonstrated that metformin could rescue the impaired migration properties and T cell regulation properties of OE-Nap1l2 BMSCs. Moreover, metformin could improve the impaired therapeutic efficacy of OE-Nap1l2 BMSCs in the treatment of colitis and experimental autoimmune encephalomyelitis in mice. Mechanistically, metformin was capable of upregulating the activation of AMPK, synthesis of l-arginine and expression of inducible nitric oxide synthase in OE-Nap1l2 BMSCs, leading to an increasing level of nitric oxide. This study indicated that Nap1l2 negatively regulated the immunomodulatory properties of BMSCs and that the impaired functions could be rescued by metformin pretreatment via metabolic reprogramming. This strategy might serve as a practical therapeutic option to rescue impaired MSCs functions for further application.

Combined Filtering Method for Offshore Oil and Gas Platform Point Cloud Data Based on KNN_PCF and Hy_WHF and Its Application in 3D Reconstruction.

With the increasing scale of deep-sea oil exploration and drilling platforms, the assessment, maintenance, and optimization of marine structures have become crucial. Traditional detection and manual measurement methods are inadequate for meeting these demands, but three-dimensional laser scanning technology offers a promising solution. However, the complexity of the marine environment, including waves and wind, often leads to problematic point cloud data characterized by noise points and redundancy. To address this challenge, this paper proposes a method that combines K-Nearest-Neighborhood filtering with a hyperbolic function-based weighted hybrid filtering. The experimental results demonstrate the exceptional performance of the algorithm in processing point cloud data from offshore oil and gas platforms. The method improves noise point filtering efficiency by approximately 11% and decreases the total error by 0.6 percentage points compared to existing technologies. Not only does this method accurately process anomalies in high-density areas-it also removes noise while preserving important details. Furthermore, the research method presented in this paper is particularly suited for processing large point cloud data in complex marine environments. It enhances data accuracy and optimizes the three-dimensional reconstruction of offshore oil and gas platforms, providing reliable dimensional information for land-based prefabrication of these platforms.

Utility of the Systemic Inflammation Response Index as a Predictor of Pneumonia After Spontaneous Intracerebral Hemorrhage.

OBJECTIVE: We sought to determine whether the initial Systemic Inflammatory Response Index (SIRI) was associated with pneumonia after spontaneous intracerebral hemorrhage (SICH) in hospitalized patients. PATIENTS AND METHODS: Patients with SICH admitted to Taizhou People's Hospital between January 2019 and December 2021 were retrospectively analyzed. Baseline variables were compared between stroke-associated pneumonia (SAP) and non-SAP groups. Multivariable logistic regression analyses were utilized to calculate the relationship between SIRI and SAP risk. RESULTS: Of 495 patients included in this research, 192 (38.79%) developed SAP ultimately. The SIRI values exhibited the highest area under the curve value for SAP incidence (area under the curve = 0.736, 95% CI: 0.692-0.781), with respective sensitivity and specificity values of 0.646 and 0.749 at the optimal cutoff threshold of 2.53. In multivariate analysis, high SIRI (≥2.53) was a significant independent predictor of post-SICH SAP even after controlling for other possible confounding variables (odds ratio: 5.11, 95% CI: 2.89-9.04, P < 0.001). According to the restricted cubic splines model, SAP risk increases as SIRI increases. CONCLUSIONS: We observed that SIRI values may offer high diagnostic utility as a predictor of SAP risk among patients with SICH during the early stages of the disease.

Development of a Clinicopathological-Radiomics Model for Predicting Progression and Recurrence in Meningioma Patients.

RATIONALE AND OBJECTIVES: Tumor progression and recurrence（P/R）after surgical resection are common in meningioma patients and can indicate poor prognosis. This study aimed to investigate the values of clinicopathological information and preoperative magnetic resonance imaging (MRI) radiomics in predicting P/R and progression-free survival (PFS) in meningioma patients. METHODS AND MATERIALS: A total of 169 patients with pathologically confirmed meningioma were included in this study, 54 of whom experienced P/R. Clinicopathological information, including age, gender, Simpson grading, World Health Organization (WHO) grading, Ki-67 index, and radiotherapy history, as well as preoperative traditional radiographic findings and radiomics features for each MRI modality (T1-weighted, T2-weighted, and enhanced T1-weighted images) were initially extracted. After feature selection, the optimal performance was estimated among the models established using different feature sets. Finally, Cox survival analysis was further used to predict PFS. RESULTS: Ki-67 index, Simpson grading, WHO grading, and radiotherapy history were found to be independent predictors for P/R in the multivariate regression analysis. This clinicopathological model had an area under the curve (AUC) of 0.865 and 0.817 in the training and testing sets, respectively. The performance of the combined radiomics model reached 0.85 and 0.84, respectively. A clinicopathological-radiomics model was then established, which significantly improved the prediction of meningioma P/R (AUC = 0.93 and 0.88, respectively). Finally, the risk ratio was estimated for each selected feature, and the C-index of 0.749 was obtained. CONCLUSION: Radiomics signatures of preoperative MRI have the ability to predict meningioma at the risk of P/R. By integrating clinicopathological information, the best performance was achieved.

Assessment of fetal intraventricular diastolic fluid dynamics using ultrasound vector flow mapping.

OBJECTIVE: The purpose of this study was to investigate the feasibility of visualizing and quantifying the normal pattern of vortex formation in the left ventricle (LV) and right ventricle (RV) of the fetal heart during diastole using vector flow mapping (VFM). METHODS: A total of 36 healthy fetuses in the second trimester (mean gestational age: 23 weeks, 2 days; range: 22-24 weeks) were enrolled in the study. Color Doppler signals were recorded in the four-chamber view to observe the phase of the diastolic vortices in the LV and RV. The vortex area and circulation were measured, and parameters such as intraventricular pressure difference (IVPD), intraventricular pressure gradient (IVPG), and average energy loss (EL_AVG) were evaluated at different diastolic phases, including isovolumic relaxation (D1), early diastole (D2), and late diastole (D3). RESULTS: Healthy second-trimester fetal vortex formations were observed in both the LV and RV at the end of diastole, with the vortices rotating in a clockwise direction towards the outflow tract. There were no significant differences in vortex area and circulation between the two ventricles (p > 0.05). However, significant differences were found in IVPD, IVPG, and EL_AVG among the diastolic phases (D1, D2, and D3) (p < 0.05). Trends in IVPD, IVPG, and EL_AVG during diastole (D1-D2-D3) revealed increasing IVPD and EL_AVG values, as well as decreasing IVPG values. Furthermore, during D3, the RV exhibited significantly higher IVPD, IVPG, and EL_AVG compared to the LV (p > 0.05). CONCLUSION: VFM is a valuable technique for analyzing the formation of vortices in the left and right ventricles during fetal diastole. The application of VFM technology has the potential to enhance the assessment of fetal cardiac parameters.

E3 ubiquitin ligase Siah1 aggravates NAFLD through Scp2 ubiquitination.

Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver disorders and accompanied by multiple metabolic dysfunctions. Although excessive lipid accumulation in hepatocytes has been identified as a crucial mediator of NAFLD development, the underlying mechanisms are very complicated and remain largely unknown. In this study, we reported that upregulated expression of the seven in absentia homolog 1 (Siah1) in the liver exacerbated NAFLD progression. Conversely, Siah1 downregulation markedly alleviated the high fat diet-induced accumulation of hepatic fat and expression of genes related to lipid metabolism in vitro and in vivo. The mechanistic study revealed that Siah1 interacted with sterol carrier protein 2 (Scp2) and promotes its ubiquitination and degradation, suggesting that Siah1 is an important activator of Scp2 ubiquitination in the context of NAFLD. Our results demonstrated that Siah1 regulated the lipid accumulation in NAFLD by interacting with Scp2. Thus, this study presents Siah1 as a promising therapeutic target in the development of NAFLD.

Brain-wide human oscillatory LFP activity during visual working memory.

Oscillatory activity is thought to be a marker of cognitive processes, although its role and distribution across the brain during working memory has been a matter of debate. To understand how oscillatory activity differentiates tasks and brain areas in humans, we recorded local field potentials (LFPs) in 12 adults as they performed visual-spatial and shape-matching memory tasks. Tasks were designed to engage working memory processes at a range of delay intervals between stimulus delivery and response initiation. LFPs were recorded using intracranial depth electrodes implanted to localize seizures for management of intractable epilepsy. Task-related LFP power analyses revealed an extensive network of cortical regions that were activated during the presentation of visual stimuli and during their maintenance in working memory, including occipital, parietal, temporal, insular, and prefrontal cortical areas, and subcortical structures including the amygdala and hippocampus. Across most brain areas, the appearance of a stimulus produced broadband power increase, while gamma power was evident during the delay interval of the working memory task. Notable differences between areas included that occipital cortex was characterized by elevated power in the high gamma (100-150 Hz) range during the 500 ms of visual stimulus presentation, which was less pronounced or absent in other areas. A decrease in power centered in beta frequency (16-40 Hz) was also observed after the stimulus presentation, whose magnitude differed across areas. These results reveal the interplay of oscillatory activity across a broad network, and region-specific signatures of oscillatory processes associated with visual working memory.