Assessing the Impact of an Artificial Intelligence-Based Model for Intracranial Aneurysm Detection in CT Angiography on Patient Diagnosis and Outcomes (IDEAL Study)-a protocol for a multicenter, double-blinded randomized controlled trial.

BACKGROUND: This multicenter, double-blinded, randomized controlled trial (RCT) aims to assess the impact of an artificial intelligence (AI)-based model on the efficacy of intracranial aneurysm detection in CT angiography (CTA) and its influence on patients' short-term and long-term outcomes. METHODS: Study design: Prospective, multicenter, double-blinded RCT. SETTINGS: The model was designed for the automatic detection of intracranial aneurysms from original CTA images. PARTICIPANTS: Adult inpatients and outpatients who are scheduled for head CTA scanning. Randomization groups: (1) Experimental Group: Head CTA interpreted by radiologists with the assistance of the True-AI-integrated intracranial aneurysm diagnosis strategy (True-AI arm). (2) Control Group: Head CTA interpreted by radiologists with the assistance of the Sham-AI-integrated intracranial aneurysm diagnosis strategy (Sham-AI arm). RANDOMIZATION: Block randomization, stratified by center, gender, and age group. PRIMARY OUTCOMES: Coprimary outcomes of superiority in patient-level sensitivity and noninferiority in specificity for the True-AI arm to the Sham-AI arm in intracranial aneurysms. SECONDARY OUTCOMES: Diagnostic performance for other intracranial lesions, detection rates, workload of CTA interpretation, resource utilization, treatment-related clinical events, aneurysm-related events, quality of life, and cost-effectiveness analysis. BLINDING: Study participants and participating radiologists will be blinded to the intervention. SAMPLE SIZE: Based on our pilot study, the patient-level sensitivity is assumed to be 0.65 for the Sham-AI arm and 0.75 for the True-AI arm, with specificities of 0.90 and 0.88, respectively. The prevalence of intracranial aneurysms for patients undergoing head CTA in the hospital is approximately 12%. To establish superiority in sensitivity and noninferiority in specificity with a margin of 5% using a one-sided α = 0.025 to ensure that the power of coprimary endpoint testing reached 0.80 and a 5% attrition rate, the sample size was determined to be 6450 in a 1:1 allocation to True-AI or Sham-AI arm. DISCUSSION: The study will determine the precise impact of the AI system on the detection performance for intracranial aneurysms in a double-blinded design and following the real-world effects on patients' short-term and long-term outcomes. TRIAL REGISTRATION: This trial has been registered with the NIH, U.S. National Library of Medicine at ClinicalTrials.gov, ID: NCT06118840 . Registered 11 November 2023.

Relations between near-field enhancements and Purcell factors in hybrid nanostructures of plasmonic antennas and dielectric cavities.

Strong near-field enhancements (NFEs) of nanophotonic structures are believed to be closely related to high Purcell factors (FP). Here, we theoretically show that the correlation is partially correct; the extinction cross section (σ) response is also critical in determining FP. The divergence between NFE and FP is especially pronounced in plasmonic-dielectric hybrid systems, where the plasmonic antenna supports dipolar plasmon modes and the dielectric cavity hosts Mie-like resonances. The cavity's enhanced-field environment can boost the antenna's NFEs, but the FP is not increased concurrently due to the larger effective σ that is intrinsic to the FP calculations. Interestingly, the peak FP for the coupled system can be predicted by using the NFE and σ responses. Furthermore, the limits for FP of coupled systems are considered; they are determined by the sum of the FP of a redshifted (or modified, if applicable) antenna and an individual cavity. This contrasts starkly with the behavior of NFE which is closely associated with the multiplicative effects of the NFEs provided by the antenna and the dielectric cavity. The differing behaviors of NFE and FP in hybrid cavities have varied impacts on relevant nanophotonic applications such as fluorescence, Raman scattering and enhanced light-matter interactions.

RGCNPPIS: A Residual Graph Convolutional Network for Protein-Protein Interaction Site Prediction.

Accurate identification of protein-protein interaction (PPI) sites is crucial for understanding the mechanisms of biological processes, developing PPI networks, and detecting protein functions. Currently, most computational methods primarily concentrate on sequence context features and rarely consider the spatial neighborhood features. To address this limitation, we propose a novel residual graph convolutional network for structure-based PPI site prediction (RGCNPPIS). Specifically, we use a GCN module to extract the global structural features from all spatial neighborhoods, and utilize the GraphSage module to extract local structural features from local spatial neighborhoods. To the best of our knowledge, this is the first work utilizing local structural features for PPI site prediction. We also propose an enhanced residual graph connection to combine the initial node representation, local structural features, and the previous GCN layer's node representation, which enables information transfer between layers and alleviates the over-smoothing problem. Evaluation results demonstrate that RGCNPPIS outperforms state-of-the-art methods on three independent test sets. In addition, the results of ablation experiments and case studies confirm that RGCNPPIS is an effective tool for PPI site prediction.

Prevalence of metabolic syndrome among patients with hepatocellular carcinoma of different etiologies: a retrospective study.

AIMS: This study compared the prevalences of metabolic syndrome and of cardiac or kidney comorbidities among patients with hepatocellular carcinoma (HCC) associated with metabolic dysfunction-related fatty liver disease (MAFLD), chronic infection with hepatitis B or C virus (HBV or HCV), or the combination of MAFLD and chronic HBV infection. METHODS: Medical records were retrospectively analyzed for patients with HCC who underwent hepatectomy between March 2013 and March 2023. Patients with HCC of different etiologies were compared in terms of their clinicodemographic characteristics and laboratory data before surgery. RESULTS: Of the 2422 patients, 1,822 (75.2%) were chronically infected with HBV without MAFLD and HCV, 415 (17.2%) had concurrent MAFLD and chronic HBV infection but no HCV infection, 121 (5.0%) had MAFLD without hepatitis virus infection, and 64 (2.6%) were chronically infected with HCV in the presence or absence of MAFLD and HBV infection. Compared to patients chronically infected with HBV without MAFLD and HCV, those with MAFLD but no hepatitis virus infection showed significantly lower prevalence of cirrhosis, ascites, portal hypertension, alpha-fetoprotein concentration ≥ 400 ng/mL, tumor size > 5 cm, multinodular tumors and microvascular invasion. Conversely, they showed significantly higher prevalence of metabolic syndrome, hypertension, type 2 diabetes, abdominal obesity, history of cardiovascular disease, T-wave alterations, hypertriglyceridemia and hyperuricemia, as well as higher risk of arteriosclerotic cardiovascular disease. Compared to patients with MAFLD but no hepatitis virus infection, those with concurrent MAFLD and chronic infection with HBV showed significantly higher prevalence of cirrhosis, ascites and portal hypertension, but significantly lower prevalence of hypertension and history of cardiovascular disease. Compared to patients with other etiologies, those chronically infected with HCV in the presence or absence of MAFLD and HBV infection, showed significantly higher prevalence of cirrhosis, portal hypertension, ascites, and esophagogastric varices. CONCLUSION: Patients with HCC associated with MAFLD tend to have a background of less severe liver disease than those with HCC of other etiologies, but they may be more likely to suffer metabolic syndrome or comorbidities affecting the heart or kidneys.

Distinct roles of TREM2 in central nervous system cancers and peripheral cancers.

Glioblastomas (GBM) are incurable central nervous system (CNS) cancers characterized by substantial myeloid cell infiltration. Whether myeloid cell-directed therapeutic targets identified in peripheral non-CNS cancers are applicable to GBM requires further study. Here, we identify that the critical immunosuppressive target in peripheral cancers, triggering receptor expressed on myeloid cells-2 (TREM2), is immunoprotective in GBM. Genetic or pharmacological TREM2 deficiency promotes GBM progression in vivo. Single-cell and spatial sequencing reveals downregulated TREM2 in GBM-infiltrated myeloid cells. TREM2 negatively correlates with immunosuppressive myeloid and T cell exhaustion signatures in GBM. We further demonstrate that during GBM progression, CNS-enriched sphingolipids bind TREM2 on myeloid cells and elicit antitumor responses. Clinically, high TREM2 expression in myeloid cells correlates with better survival in GBM. Adeno-associated virus-mediated TREM2 overexpression impedes GBM progression and synergizes with anti-PD-1 therapy. Our results reveal distinct functions of TREM2 in CNS cancers and support organ-specific myeloid cell remodeling in cancer immunotherapy.

Pre-PCI CT-FFR Predicts Target Vessel Failure After Stent Implantation.

OBJECTIVES: To investigate the predictive value of coronary computed tomography angiography-derived fractional flow reserve (CT-FFR) before percutaneous coronary intervention (PCI) to predict target vessel failure (TVF) after stent implantation. METHODS: This retrospective study included 429 patients (429 vessels) who underwent PCI and stent implantation after CCTA within 3 months. All patients underwent coronary stent implantation between January 2012 and December 2019. A dedicated workstation (Syngo Via, Siemens) was used to analyze and measure the CT-FFR value. The cut-off values of pre-PCI CT-FFR for predicting TVF were defined as 0.80 and the value using the log-rank maximization method, respectively. The primary outcome was TVF, defined as a composite of cardiac death, target vessel myocardial infarction, and clinically driven target vessel revascularization (TVR), which was a secondary outcome. RESULTS: During a median 64.0 months follow-up, the cumulative incidence of TVF was 7.9% (34/429). The cutoff value of pre-PCI CT-FFR based on the log-rank maximization method was 0.74, which was the independent predictor for TVF [hazard ratio (HR): 2.61 (95% CI: 1.13, 6.02); P=0.024] and TVR [HR: 3.63 (95%CI: 1.25, 10.51); P=0.018]. Compared with the clinical risk factor model, pre-PCI CT-FFR significantly improved the reclassification ability for TVF [net reclassification improvement (NRI), 0.424, P<0.001; integrative discrimination index (IDI), 0.011, P=0.022]. Adding stent information to the prediction model resulted in an improvement in reclassification for the TVF (C statistics: 0.711, P=0.001; NRI: 0.494, P<0.001; IDI: 0.020, P=0.028). CONCLUSIONS: Pre-PCI CT-FFR ≤0.74 was an independent predictor for TVF or TVR, and integration of clinical, pre-PCI CT-FFR, and stent information models can provide a better risk stratification model in patients with stent implantation.

Integrated identification-quantification (ID-Quant) workflow utilizing UPLC-QTOF-MS for the therapeutic drug monitoring of multi-component antibiotics without pure standards: Validation using teicoplanin.

The lack of individual pure standard has hampered the application of therapeutic drug monitoring (TDM) for multi-component antibiotics in clinical laboratories. Here, we aimed to develop an integrated identification-quantification (ID-Quant) workflow based on ultra-high-performance liquid chromatography coupled with quadrupole/time-of-flight mass spectrometry (UHPLC-QTOF-MS) to enable the comprehensive determination of all teicoplanin components without needing pure standards. The workflow comprises three steps. First, non-targeted MSE full scanning was used to detect and identify all potential ingredients. Then, characteristic product ions were selected to generate a quantitative time-of-flight multiple reaction monitoring (Tof-MRM) method. Finally, the constituent composition of teicoplanin injection was determined and utilized as an alternative reference standard to monitor the teicoplanin ingredients in human serum samples. As a result, nine teicoplanin analogs were identified from teicoplanin injection (Sanofi-Aventis, France). The overall performance of the Tof-MRM method was satisfactory in terms of linearity, precision, accuracy, and limits of detection. Utilizing the drug as standard, the individual concentrations for each component in patient serum were determined to be 0.120 µg/mL (A3-1), 0.020 µg/mL (N-1), 0.550 µg/mL (N-2), 0.730 µg/mL (A2-1), 4.26 µg/mL (A2-2,3), 4.79 µg/mL (A2-4,5), and 0.290 µg/mL (N-3), respectively. The distribution pattern of teicoplanin components was also discovered to differ from that in the drug injection. Overall, this integrated ID-Quant workflow based on UHPLC-QTOF-MS enables the robust quantitation of all teicoplanin analogs without the need for individual pure standard. This approach could help address the standard unavailability problem in the TDM of multi-component antibiotics.

The patterns and risk factors of relapse in oesophageal squamous cell cancers who achieve pathologic complete response to neoadjuvant chemoradiotherapy.

BACKGROUND: This study aimed to investigate the patterns and risk factors for recurrence in oesophageal squamous cell carcinoma (ESCC) patients with pathologic complete response after neoadjuvant chemoradiotherapy (nCRT). METHODS: Between January 2008 and December 2018, a total of 96 patients with pCR were enrolled in this study. Lymph nodes with pathologic complete response (LN-ypCR response (+)) were defined as those lymph nodes without residual tumour but with the presence of treatment response to nCRT. Prognostic factors for recurrence-free survival (RFS) were analyzed with Cox proportional hazards models and the Fine-Gray competing risk models. Lymph nodes (LN) stations were counted according to Japan Oesophageal Society (JES) classification. RESULTS: The median follow-up time was 51.5 months. Recurrence occurred in 15 cases (15.6%) with a 9.9 months median time to recurrence and a 15.6 months median survival after recurrence. The most majority of recurrent diseases developed within the first 2 years after surgery. Distant recurrences were detected in 14 cases (14.6%), in which the most common recurrence sites were no.104 LN and lung, followed by no.16 LN. The mean RFS in the whole cohort was 116.6 months. LN-ypCR response (+) was identified as the independently prognostic factor for worse RFS in both of multivariate Cox model and Fine-Gray competing risk model (P = 0.001 and P = 0.002, respectively). CONCLUSIONS: Relapse is not rare in ESCC cases with pCR after nCRT. Distant recurrences, the predominant pattern of relapse, mostly occur within the first 2 years after oesophagectomy. pCR patients with LN-ypCR response (+) have a higher risk for postoperative recurrence.

Minimally invasive esophagectomy with non-invasive ventilation by laryngeal mask-assisted anesthesia for esophageal squamous cell carcinoma: case report.

Minimally invasive esophagectomy for cancer surgery remains associated with significant morbidity and surgical complications across the globe. Non-intubation video-assisted thoracic surgery (NIVATS) has been successfully employed in lung resection in recent years, but there are few reported cases with regard to the safety and feasibility of this approach in radical esophagectomy for patients with esophageal cancers. We present 4 consecutive cases with esophageal squamous cell carcinoma (ESCC) who received minimally invasive McKeown's esophagectomy under non-intubation general anesthesia from November 2022 to April 2023. All these patients were aged from 55 to 75 years old and were pathologically diagnosed with ESCC. All procedures of McKeown's esophagectomy in these patients were completed with non-invasive ventilation by laryngeal mask-assisted anesthesia. Operation duration ranged from 185 to 395 minutes and the estimated blood loss ranged from 25 to 60 ml in these 4 cases. No severe hypoxia was observed and transient hypercapnia was resolved intraoperatively. None of them was converted to endotracheal intubation with mechanical ventilation or to thoracotomy. The number of retrieved lymph nodes in mediastinum were 21-27 and all patients received R0 surgery with pathological stage as T1bN0M0 to T3N2M0. There was no serious complication (Clavien-Dindo grade III-IV) observed perioperatively and they were all discharged 11-14 days after the surgery with resumption of oral feeding. They are all alive without tumor recurrence at the date of data collection. The safety and efficacy of minimally invasive esophagectomy with non-invasive ventilation by laryngeal mask-assisted anesthesia for patients with ESCC are warranted for explored in a larger cohort study.

Tilapia head gelatins to stabilize fish oil emulsions and the effect of extraction methods.

The preparation and use of gelatins from fish by-products have attracted much attention in the field of food science. Herein, four types of tilapia head gelatins were extracted and characterized: hot water-pretreated gelatin (HWG), acetic acid-pretreated gelatin (AAG), sodium hydroxide-pretreated gelatin (SHG), and pepsin enzyme-pretreated gelatin (PEG). The gel strength values followed the order: PEG (74 ± 1 Bloom) > AAG (66 ± 1) > HWG (59 ± 1) > SHG (34 ± 1). The foaming properties, fish oil emulsion viscosity, emulsion activity, and emulsion stabilization ability followed this order: PEG > HWG ≥ AAG > SHG. The effect mechanisms of extraction methods and gelatin concentrations on the emulsion stability involved the interfacial tension, emulsion viscosity, and fat-binding capacity. This work provided important knowledge for analyzing the relations between the structure and function of gelatin. It also provided a high-value application method of fish wastes.

Coping with alpine habitats: genomic insights into the adaptation strategies of Triplostegia glandulifera (Caprifoliaceae).

How plants find a way to thrive in alpine habitats remains largely unknown. Here we present a chromosome-level genome assembly for an alpine medicinal herb, Triplostegia glandulifera (Caprifoliaceae), and 13 transcriptomes from other species of Dipsacales. We detected a whole-genome duplication event in T. glandulifera that occurred prior to the diversification of Dipsacales. Preferential gene retention after whole-genome duplication was found to contribute to increasing cold-related genes in T. glandulifera. A series of genes putatively associated with alpine adaptation (e.g. CBFs, ERF-VIIs, and RAD51C) exhibited higher expression levels in T. glandulifera than in its low-elevation relative, Lonicera japonica. Comparative genomic analysis among five pairs of high- vs low-elevation species, including a comparison of T. glandulifera and L. japonica, indicated that the gene families related to disease resistance experienced a significantly convergent contraction in alpine plants compared with their lowland relatives. The reduction in gene repertory size was largely concentrated in clades of genes for pathogen recognition (e.g. CNLs, prRLPs, and XII RLKs), while the clades for signal transduction and development remained nearly unchanged. This finding reflects an energy-saving strategy for survival in hostile alpine areas, where there is a tradeoff with less challenge from pathogens and limited resources for growth. We also identified candidate genes for alpine adaptation (e.g. RAD1, DMC1, and MSH3) that were under convergent positive selection or that exhibited a convergent acceleration in evolutionary rate in the investigated alpine plants. Overall, our study provides novel insights into the high-elevation adaptation strategies of this and other alpine plants.

Adjuvant Therapy for Hepatocellular Carcinoma After Curative Treatment: Several Unanswered Questions.

Most patients with hepatocellular carcinoma (HCC) have a poor prognosis. Hepatectomy and local ablation are the main curative treatments for HCC. Nevertheless, the recurrence rate after hepatectomy or ablation is up to 70%, which seriously affects patient prognosis. Several adjuvant therapies have been explored to reduce postoperative recurrence. However, although a variety of adjuvant therapies have been shown to reduce the recurrence rate and improve overall survival, a standard consensus of national HCC guidelines for adjuvant treatment is lacking. Therefore, there are significant differences in the recommendations for adjuvant therapy for HCC between the Eastern and Western guidelines. A variety of adjuvant treatment methods, such as antiviral therapy, transarterial chemoembolization or traditional Chinese medicine, are recommended by the Chinese HCC guidelines. However, Western guidelines make few recommendations other than antiviral therapy. Adjuvant immune checkpoint inhibitors are recommended only in the recently updated American Association for the Study of Liver Diseases guidelines. This review summarized the existing adjuvant therapy options after curative hepatectomy or ablation and discusses several important dilemmas of adjuvant treatments.

Genome-Wide Identification and Expression Pattern Analysis of TIFY Family Genes Reveal Their Potential Roles in Phalaenopsis aphrodite Flower Opening.

The TIFY gene family (formerly known as the zinc finger proteins expressed in inflorescence meristem (ZIM) family) not only functions in plant defense responses but also are widely involved in regulating plant growth and development. However, the identification and functional analysis of TIFY proteins remain unexplored in Orchidaceae. Here, we identified 19 putative TIFY genes in the Phalaenopsis aphrodite genome. The phylogenetic tree classified them into four subfamilies: 14 members from JAZ, 3 members from ZML, and 1 each from PPD and TIFY. Sequence analysis revealed that all Phalaenopsis TIFY proteins contained a TIFY domain. Exon-intron analysis showed that the intron number and length of Phalaenopsis TIFY genes varied, whereas the same subfamily and subgroup genes had similar exon or intron numbers and distributions. The most abundant cis-elements in the promoter regions of the 19 TIFY genes were associated with light responsiveness, followed by MeJA and ABA, indicating their potential regulation by light and phytohormones. The 13 candidate TIFY genes screened from the transcriptome data exhibited two types of expression trends, suggesting their different roles in cell proliferation and cell expansion of floral organ growth during Phalaenopsis flower opening. Overall, this study serves as a background for investigating the underlying roles of TIFY genes in floral organ growth in Phalaenopsis.

Juglone triggers apoptosis of non-small cell lung cancer through the reactive oxygen species -mediated PI3K/Akt pathway.

Non-small cell lung cancer (NSCLC) is one of the most common malignancies worldwide, and oxidative stress plays a crucial role in its development. Juglone, a naturally occurring naphthoquinone in J. mandshurica, exhibits significant cytotoxic activity against various cancer cell lines. However, whether the anticancer activity of juglone is associated with oxidative stress remains unexplored. In this study, mouse Lewis lung cancer (LLC) and human non-small cell lung cancer A549 cells were used to explore the anticancer mechanisms of juglone. Juglone inhibited LLC and A549 cells viability, with IC50 values of 10.78 µM and 9.47 µM, respectively, for 24 h, and substantially suppressed the migration and invasion of these two lung cancer cells. Additionally, juglone arrested the cell cycle, induced apoptosis, increased the cleavage of caspase 3 and the protein expression of Bax and Cyt c, and decreased the protein expression of Bcl-2 and caspase-3. Furthermore, juglone treatment considerably increased intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) levels, but suppressed glutathione peroxidase 4 (GPX4) and superoxide dismutase (SOD) activities. It also inhibited the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway, which was attenuated by 1,3-diCQA (an activator of PI3K/Akt). Moreover, N-acetylcysteine (a ROS scavenger) partially reversed the positive effects of juglone in terms of migration, invasion, ROS production, apoptosis, and PI3K/Akt pathway-associated protein expression. Finally, in tumor-bearing nude mouse models, juglone inhibited tumor growth without any apparent toxicity and significantly induced apoptosis in NSCLC cells. Collectively, our findings suggest that juglone triggers apoptosis via the ROS-mediated PI3K/Akt pathway. Therefore, juglone may serve as a potential therapeutic agent for the treatment of NSCLC.

Regional impact assessment of air quality improvement: The air quality lifecourse assessment tool (AQ-LAT) for the West Midlands combined authority (WMCA) area.

Poor air quality is the largest environmental health risk in England. In the West Midlands, UK, ∼2.9 million people are affected by air pollution with an average loss in life expectancy of up to 6 months. The 2021 Environment Act established a legal framework for local authorities in England to develop regional air quality plans, generating a policy need for predictive environmental impact assessment tools. In this context, we developed a novel Air Quality Lifecourse Assessment Tool (AQ-LAT) to estimate electoral ward-level impacts of PM2.5 and NO2 exposure on outcomes of interest to local authorities, namely morbidity (asthma, coronary heart disease (CHD), stroke, lung cancer), mortality, and associated healthcare costs. We apply the Tool to assess the health economic burden of air pollutant exposure and estimate benefits that would be generated by meeting WHO 2021 Global Air Quality Guidelines (AQGs) (annual average concentrations) for NO2 (10 µg/m3) and PM2.5 (5 µg/m3) in the West Midlands Combined Authority Area. All West Midlands residents live in areas which exceed WHO AQGs, with 2070 deaths, 2070 asthma diagnoses, 770 CHD diagnoses, 170 lung cancers and 650 strokes attributable to air pollution exposure annually. Reducing PM2.5 and NO2 concentrations to WHO AQGs would save 10,700 lives reducing regional mortality by 1.8%, gaining 92,000 quality-adjusted life years (QALYs), and preventing 20,500 asthma, 7400 CHD, 1400 lung cancer, and 5700 stroke diagnoses, with economic benefits of £3.2 billion over 20 years. Significantly, we estimate 30% of QALY gains relate to reduced disease burden. The AQ-LAT has major potential to be replicated across local authorities in England and applied to inform regional investment decisions.

Genome-wide characterization and expression profiling of the HD-ZIP gene family in Acoraceae under salinity and cold stress.

The Homeodomain-Leucine Zipper (HD-ZIP) transcription factors play a pivotal role in governing various aspects of plant growth, development, and responses to abiotic stress. Despite the well-established importance of HD-ZIPs in many plants, their functions in Acoraceae, the basal lineage of monocots, remain largely unexplored. Using recently published whole-genome data, we identified 137 putative HD-ZIPs in two Acoraceae species, Acorus gramineus and Acorus calamus. These HD-ZIP genes were further classified into four subfamilies (I, II, III, IV) based on phylogenetic and conserved motif analyses, showcasing notable variations in exon-intron patterns among different subfamilies. Two microRNAs, miR165/166, were found to specifically target HD-ZIP III genes with highly conserved binding sites. Most cis-acting elements identified in the promoter regions of Acoraceae HD-ZIPs are involved in modulating light and phytohormone responsiveness. Furthermore, our study revealed an independent duplication event in Ac. calamus and a one-to-multiple correspondence between HD-ZIP genes of Ac. calamus and Ac. gramineus. Expression profiles obtained from qRT-PCR demonstrated that HD-ZIP I genes are strongly induced by salinity stress, while HD-ZIP II members have contrasting stress responses in two species. HD-ZIP III and IV genes show greater sensitivity in stress-bearing roots. Taken together, these findings contribute valuable insights into the roles of HD-ZIP genes in stress adaptation and plant resilience in basal monocots, illuminating their multifaceted roles in plant growth, development, and response to abiotic stress.

Spatial confinement modulates endothelial cell behavior and traction force in 3D hydrogel microgrooves.

The mechanical environment of vascular endothelial cells (ECs) encompasses a wide range of curvatures due to variations in blood vessel diameters. Integrins, key mediators of cell-matrix interactions, establish connections between the extracellular matrix and the actin cytoskeleton, influencing diverse cellular behaviors. In this study, we explored the impact of spatial confinement on human umbilical vein ECs (HUVECs) cultured within three-dimensional hydrogel microgrooves of varying curvatures and the underlying role of integrins in mediating cellular responses. Employing maskless lithography, we successfully fabricated precise and wall curvatures-controlled hydrogel microgrooves, conferring spatial constraints on the cells. Our investigations revealed substantial alterations in HUVEC behavior within the hydrogel microgrooves with varying sidewall curvatures, marked by reduced cell size, enhanced orientation, and increased apoptosis. Interestingly, microgroove curvature emerged as a crucial factor influencing cell orientation and apoptosis, with rectangular microgrooves eliciting distinct changes in cell orientation, while ring-form microgrooves exhibited higher apoptosis rates. The side-wall effect in the 20 µm region near the microgroove wall had the greatest influence on cell orientation and apoptosis. HUVECs within the microgrooves exhibited elevated integrin expression, and inhibition of αV-integrin by cilengitide significantly curtailed cell apoptosis without affecting proliferation. Additionally, integrin-mediated cell traction force closely correlated with the spatial confinement effect. Cilengitide not only reduced integrin and focal adhesion expression but also attenuated cell traction force and cytoskeletal actin filament alignment. Overall, our findings elucidate the spatial confinement of ECs in hydrogel microgrooves and underscores the pivotal role of integrins, particularly αV-integrin, in mediating cell traction force and apoptosis within this microenvironment.

Global prevalence of MAFLD-related hepatocellular carcinoma: A systematic review and meta-analysis.

BACKGROUND & AIMS: The global proportion of hepatocellular carcinoma (HCC) attributable to metabolic dysfunction-associated fatty liver disease (MAFLD) is unclear. The MAFLD diagnostic criteria allows objective diagnosis in the presence of steatosis plus defined markers of metabolic dysfunction, irrespective of concurrent liver disease. We aimed to determine the total global prevalence of MAFLD in HCC cohorts (total-MAFLD), including the proportion with MAFLD as their sole liver disease (single-MAFLD), and the proportion of those with concurrent liver disease where MAFLD was a contributary factor (mixed-MAFLD). METHODS: This systematic review and meta-analysis included studies systematically ascertaining MAFLD in HCC cohorts, defined using international expert panel criteria including ethnicity specific BMI cut-offs. A comparison of clinical and tumour characteristics was performed between single-MAFLD, mixed-MAFLD and non-MAFLD HCC. RESULTS: 22 studies (56,565 individuals with HCC) were included. Total and single-MAFLD HCC prevalence was 48.7% (95% CI; 34.5% - 63.0%) and 12.4% (95% CI; 8.3% - 17.3%), respectively. In HCC due to chronic hepatitis B, C and alcohol-related liver disease, mixed-MAFLD prevalence was 40.0% (95% CI; 30.2% - 50.3%), 54.1% (95% CI; 40.4% - 67.6%) and 64.3% (95% CI; 52.7% - 75.0%), respectively. Mixed-MAFLD HCC had significantly higher likelihood of cirrhosis and lower likelihood of metastatic spread compared to single-MAFLD HCC, and a higher platelet count and lower likelihood of macrovascular invasion compared to non-MAFLD HCC. CONCLUSION: MAFLD is common as a sole aetiology, but more so and as a co-factor in mixed-aetiology HCC, supporting the use of a positive diagnostic criteria.

Statistical Genomics Analysis of Simple Sequence Repeats from the Paphiopedilum Malipoense Transcriptome Reveals Control Knob Motifs Modulating Gene Expression.

Simple sequence repeats (SSRs) are found in nonrandom distributions in genomes and are thought to impact gene expression. The distribution patterns of 48 295 SSRs of Paphiopedilum malipoense are mined and characterized based on the first full-length transcriptome and comprehensive transcriptome dataset from 12 organs. Statistical genomics analyses are used to investigate how SSRs in transcripts affect gene expression. The results demonstrate the correlations between SSR distributions, characteristics, and expression level. Nine expression-modulating motifs (expMotifs) are identified and a model is proposed to explain the effect of their key features, potency, and gene function on an intra-transcribed region scale. The expMotif-transcribed region combination is the most predominant contributor to the expression-modulating effect of SSRs, and some intra-transcribed regions are critical for this effect. Genes containing the same type of expMotif-SSR elements in the same transcribed region are likely linked in function, regulation, or evolution aspects. This study offers novel evidence to understand how SSRs regulate gene expression and provides potential regulatory elements for plant genetic engineering.

Fish oil-loaded multicore submillimeter-sized capsules prepared with monoaxial electrospraying, chitosan-tripolyphosphate ionotropic gelation, and Tween blending.

In order to load fish oil for potential encapsulation of fat-soluble functional active substances, fish oil-loaded multicore submillimeter-sized capsules were prepared with a combination method of three strategies (monoaxial electrospraying, chitosan-tripolyphosphate ionotropic gelation, and Tween blending). The chitosan-tripolyphosphate/Tween (20, 40, 60, and 80) capsules had smaller and evener fish oil cores than the chitosan-tripolyphosphate capsules, which resulted from that Tween addition induced smaller and evener fish oil droplets in the emulsions. Tween addition decreased the water contents from 56.6 % to 35.0 %-43.4 %, increased the loading capacities from 10.4 % to 12.7 %-17.2 %, and increased encapsulation efficiencies from 97.4 % to 97.8 %-99.1 %. In addition, Tween addition also decreased the highest peroxide values from 417 meq/kg oil to 173-262 meq/kg oil. These properties' changes might result from the structural differences between the chitosan-tripolyphosphate and chitosan-tripolyphosphate/Tween capsules. All the results suggested that the obtained chitosan-tripolyphosphate/Tween capsules are promising carriers for fish oil encapsulation. This work also provided useful knowledge to understand the preparation, structural, and physicochemical properties of the chitosan-tripolyphosphate capsules.