Changes of serum cortisol during pregnancy and labor initiation: an onsite cross-sectional study.

Background: Increased maternal cortisol secretion has been observed during pregnancy and labor. However, due to the limitations in diagnostic methods, the dynamic change of cortisol during the short period between threatened labor and labor is unknown. In this study, we aim to evaluate the changes in serum cortisol during late pregnancy and full-term labor initiation, verifying if cortisol could serve as a biomarker for the diagnosis of labor initiation from threatened labor. Methods: This cross-sectional onsite study involved 564 participants of 6 different gestational stages (C: Control; T1: Trimester 1; T3: Trimester 3; E: expectant; TL: threatened labor; L: labor), all patients in the E, TL, and L groups were at full term. The serum cortisol concentration was quantified with a point-of-care test (POCT), and the gestation, age, parity, and BMI of participants were documented. Morning serum cortisol was collected between 8:00 and 10:00 a.m., except for the TL and L group women who were tested upon arrival or during latent labor. With cortisol levels or all five variables, L was distinguished from TL using machine learning algorithms. Results: Significant elevation of cortisol concentration was observed between T1 and T3, or TL and L group (P< 0.001). Women belonging to the E and TL group showed similar gestation week and cortisol levels. Diagnosis of labor initiation using cortisol levels (cutoff = 21.46 µg/dL) yielded sensitivity, specificity, and AUC of 86.50%, 88.60%, and 0.934. With additional variables, a higher specificity (89.29%) was achieved. The diagnostic accuracy of all methods ranged from 85.93% to 87.90%. Conclusion: Serum cortisol could serve as a potential biomarker for diagnosis of L form TL. The rapid onsite detection of serum cortisol with POCT could facilitate medical decision-making for admission and special treatments, either as an additional parameter or when other technical platforms are not available.

Preliminary study on the diagnostic value of LEAP-2 and CK18 in biopsy-proven MAFLD.

Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) has become the leading cause of chronic liver disease. Liver biopsy, as the diagnostic gold standard, is invasive and has sampling bias, making it particularly important to search for sensitive and specific biomarkers for diagnosis. Cytokeratin 18 (CK18) M30 and M65 are products of liver cell apoptosis and necrosis, respectively, and liver-expressed antimicrobial peptide 2 (LEAP-2) is a related indicator of glucose and lipid metabolism. Correlation studies have found that all three indicators positively correlate with the liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Through comparison of diagnostic values, it was found that CK18 M65 can better distinguish between healthy individuals and MAFLD; LEAP-2 can effectively distinguish MAFLD from other liver diseases, especially ALD.

The Role and Mechanism of Nicotinamide Riboside in Oxidative Damage and a Fibrosis Model of Trabecular Meshwork Cells.

Purpose: To investigate the potential effects and mechanism of nicotinamide riboside (NR) on the oxidative stress and fibrosis model of human trabecular meshwork (HTM) cell line cells. Methods: HTM cells were pretreated with NR, followed by the induction of oxidative injury and fibrosis by hydrogen peroxide (H2O2) and TGF-ß2, respectively. Cell viability was tested using Hoechst staining and MTT assays, cell proliferation was assessed by EdU assay, and cell apoptosis was detected by flow cytometry and western blotting. DCFH-DA and DHE probes were used to measure the level of reactive oxygen species (ROS), and MitoTracker staining was used to measure the mitochondrial membrane potential (MMP). Fibrotic responses, including cell migration and deposition of extracellular matrix (ECM) proteins, were detected via Transwell assays, qRT-PCR, and immunoblotting. Results: NR pretreatment improved the viability, proliferation, and MMP of H2O2-treated HTM cells. Compared to cells treated solely with H2O2, HTM cells treated with both NR and H2O2, exhibited a reduced rate of apoptosis and generation of ROS. Compared with H2O2 pretreatment, NR pretreatment upregulated expression of the JAK2/Stat3 pathway but inhibited mitogen-activated protein kinase (MAPK) pathway expression. Moreover, 10-ng/mL TGF-ß2 promoted cell proliferation and migration, which were inhibited by NR pretreatment. Both qRT-PCR and immunoblotting showed that NR inhibited the expression of fibronectin in a TGF-ß2-induced fibrosis model. Conclusions: NR has a protective effect on oxidative stress and fibrosis in HTM cells, which may be related to the JAK2/Stat3 pathway and MAPK pathway. Translational Relevance: Our research provides the ongoing data for potential therapy of NAD+ precursors in glaucoma.

AIEgens-enhanced rapid sensitive immunofluorescent assay for SARS-CoV-2 with digital microfluidics.

BACKGROUND: Sensitive and rapid antigen detection is critical for the diagnosis and treatment of infectious diseases, but conventional ELISAs including chemiluminescence-based assays are limited in sensitivity and require many operation steps. Fluorescence immunoassays are fast and convenient but often show limited sensitivity and dynamic range. RESULTS: To address the need, an aggregation-induced emission fluorgens (AIEgens) enhanced immunofluorescent assay with beads-based quantification on the digital microfluidic (DMF) platform was developed. Portable DMF devices and chips with small electrodes were fabricated, capable of manipulating droplets within 100 nL and boosting the reaction efficiency. AIEgen nanoparticles (NPs) with high fluorescence and photostability were synthesized to enhance the test sensitivity and detection range. The integration of AIEgen probes, transparent DMF chip design, and the large magnetic beads (10 µm) as capture agents enabled rapid and direct image-taking and signal calculation of the test result. The performance of this platform was demonstrated by point-of-care quantification of SARS-CoV-2 nucleocapsid (N) protein. Within 25 min, a limit of detection of 5.08 pg mL-1 and a limit of quantification of 8.91 pg mL-1 can be achieved using <1 µL sample. The system showed high reproducibility across the wide dynamic range (10-105 pg mL-1), with the coefficient of variance ranging from 2.6% to 9.8%. SIGNIFICANCE: This rapid, sensitive AIEgens-enhanced immunofluorescent assay on the DMF platform showed simplified reaction steps and improved performance, providing insight into the small-volume point-of-care testing of different biomarkers in research and clinical applications.

Associations of recurrent lumbar disc herniation after percutaneous endoscopic lumbar discectomy with age, body mass index, modic change, disc degeneration and sacral slope: A quantitative review.

Recurrent lumbar disc herniation (rLDH) seriously affects the quality of life of patients and increases the medical burden. The purpose of the present study was to determine the risk factors for rLDH after percutaneous endoscopic lumbar discectomy (PELD). The PubMed, Cochrane Library and Embase databases were searched for studies on the factors associated with rLDH after PELD. The databases were searched from inception to March 30, 2023. The combined effects of categorical variables and continuous variables were measured using odds ratios (ORs) and weighted mean differences (WMDs), respectively, and their corresponding 95% confidence intervals (CIs) were calculated. RevMan 5.3 software was used for data analysis. A total of 9 case-control studies were included in this meta-analysis, comprising 5,446 patients. This study explored a total of 18 potential risk factors for rLDH after PELD; ultimately, 5 factors were associated with the risk of rLDH. Meta-analysis showed that older age (WMD=6.49, 95% CI: 2.52 to 10.46), greater body mass index (WMD=1.16, 95% CI: 0.69 to 1.62), modic change (OR=2.48, 95% CI: 1.54 to 3.99), Pfirrmann grade ≥4 (OR=2.84, 95% CI: 1.3 to 6.16) and greater sacral slope angle (WMD=3.48, 95% CI: 0.53 to 6.42) were risk factors for rLDH after PELD. The risk factors identified in the present study may enable clinicians to identify high-risk populations early and to select appropriate surgical procedures to reduce the risk of rLDH. Perioperative interventions targeting the modifiable factors identified in this study may be beneficial for reducing the risk of rLDH.

Impact of glioma peritumoral edema, tumor size, and tumor location on alternating electric fields (AEF) therapy in realistic 3D rat glioma models: a computational study.

Objective.Alternating electric fields (AEF) therapy is a treatment modality for patients with glioblastoma. Tumor characteristics such as size, location, and extent of peritumoral edema may affect the AEF strength and distribution. We evaluated the sensitivity of the AEFs in a realistic 3D rat glioma model with respect to these properties.Approach.The electric properties of the peritumoral edema were varied based on calculated and literature-reported values. Models with different tumor composition, size, and location were created. The resulting AEFs were evaluated in 3D rat glioma models.Main results.In all cases, a pair of 5 mm diameter electrodes induced an average field strength >1 V cm-1. The simulation results showed that a negative relationship between edema conductivity and field strength was found. As the tumor core size was increased, the average field strength increased while the fraction of the shell achieving >1.5 V cm-1decreased. Increasing peritumoral edema thickness decreased the shell's mean field strength. Compared to rostrally/caudally, shifting the tumor location laterally/medially and ventrally (with respect to the electrodes) caused higher deviation in field strength.Significance.This study identifies tumor properties that are key drivers influencing AEF strength and distribution. The findings might be potential preclinical implications.

Comparison of the quality of Nurse-Led palliative care with standard medical care during six months in 405 patients with Parkinson's disease and burdens of their Caregivers: A retrospective study at a single center in China.

BACKGROUND: Palliative care is mainly used to improve the quality of life of patients with chronic diseases by addressing their medical conditions and psychological problems. End-stage Parkinson's disease (PD) is also a progressive disease like cancer and could be managed by palliative care. This study was conducted at a single center in China and aimed to compare the quality of nurse-led palliative care with standard medical care during six months in 405 patients with Parkinson's disease (PPD) and their caregivers using the Chinese version of the 39-item Parkinson's Disease Questionnaire (PDQ-39) and the Chinese Zarit Burden Interview (ZBI) scale. METHODS: PPD (stage 2-5) received nurse-led palliative care (NP cohort, 103 patients; 103 caregivers) or neurologist-led standard care (NS cohort, 134 patients; 134 caregivers), or primary care practitioner-led usual care (PS cohort, 168 patients; 168 caregivers) for six months. RESULTS: Before the health professional-led care (BN), the PDQ-39 score of PPD was 68 (71-64) and their caregivers had 54.86 ± 7.64 a ZBI scale. After 6-months of the health professional-led care (AN), the PDQ-39 score of PPD and a ZBI scale of their caregivers decreased for the NP cohort as compared to those of BN condition and those of patients in the NS and PS cohorts at AN condition (p < 0.001 for all). CONCLUSIONS: The quality of life of PPD must be improved and the burden on their caregivers must be relieved. Nurse-led palliative care successfully improved the quality of life of PPD and reduced their caregiver burden.

Studies on the transfer effect of aged polyethylene microplastics in soil-plant system.

The widespread use of polyethylene (PE) agricultural films has led to a large accumulation of microplastics in soil, and the environmental effects of microplastics on soil-plants have received increasing attention. In the actual soil environment, microplastics undergo significant changes in their physicochemical properties due to aging, accompanied by complex ecological and environmental effects. However, the quantitative understanding of the environmental effects of microplastic aging in soil-plant systems is still unclear. Therefore, this study investigated the effects of aged and unaged PE microplastics on ecological functions and microplastic transfer mechanisms in soil-plant system, and confirmed the transport behavior of micrometer-sized microplastics (26 µm) within maize plants, expanding the upper size limit of existing studies on microplastic transport within plants. The accumulation of microplastics in maize was also quantitatively assessed in combination with the self-established method of Eu marked PE. The mobility ratio of microplastics from soil to roots, roots to stems, and stems to leaves was 1.07%, 0.76%, and 103.28%, respectively. This study provides a scientific understanding for the environmental effects of microplastics in soil-plants systems quantitatively.

The effect of different prebiotics on intestinal probiotics in newly diagnosed diabetic patients.

Prebiotics exert favorable effects on the host through interactions with probiotics, and their beneficial impacts have been extensively validated across various chronic ailments, including diabetes. This study presents findings from a case-control investigation involving 10 individuals with type 2 diabetes mellitus (T2DM) and 10 healthy counterparts. Fresh stool specimens were collected from all participants. Following a 24-h fermentation period in mediums containing xylitol and mannitol, the observed increase in Lactobacillus abundance within the case group exceeded that of the control group. Similarly, in mediums containing soluble starch, choline, and L-carnitine, the augmentation of Bifidobacterium within the case group surpassed that of the controls. Notably, a statistically significant divergence in sugar degradation rate emerged between the case and control groups, specifically in the medium harboring lactulose and isomalto-oligosaccharides. Remarkably, the degradation rate of lactulose exhibited a positive correlation with the expansion of Bifidobacterium (R 2 = .147, p = .037). Likewise, the degradation rate of isomalto-oligosaccharides demonstrated a positive correlation with Bifidobacterium proliferation (R 2 = .165, p = .041). In conclusion, prebiotics like xylitol and mannitol exhibit the capacity to enhance intestinal probiotic populations in individuals newly diagnosed with diabetes. The modifications in the intestinal flora homeostasis of diabetic patients may be evidenced by alterations in the degradation rate of specific prebiotic substrates.

Advanced design and applications of digital microfluidics in biomedical fields: An update of recent progress.

Significant breakthroughs have been made in digital microfluidic (DMF)-based technologies over the past decades. DMF technology has attracted great interest in bioassays depending on automatic microscale liquid manipulations and complicated multi-step processing. In this review, the recent advances of DMF platforms in the biomedical field were summarized, focusing on the integrated design and applications of the DMF system. Firstly, the electrowetting-on-dielectric principle, fabrication of DMF chips, and commercialization of the DMF system were elaborated. Then, the updated droplets and magnetic beads manipulation strategies with DMF were explored. DMF-based biomedical applications were comprehensively discussed, including automated sample preparation strategies, immunoassays, molecular diagnosis, blood processing/testing, and microbe analysis. Emerging applications such as enzyme activity assessment and DNA storage were also explored. The performance of each bioassay was compared and discussed, providing insight into the novel design and applications of the DMF technology. Finally, the advantages, challenges, and future trends of DMF systems were systematically summarized, demonstrating new perspectives on the extensive applications of DMF in basic research and commercialization.

Early enteral nutrition intervention promotes multiple functional recovery in patients with traumatic intracerebral hemorrhage: A prospective randomized controlled study.

OBJECTIVE: To delve into how early enteral nutrition intervention exert its part in promoting multiple functional recovery in patients with traumatic intracerebral hemorrhage (TICH). METHOD: This prospective randomized controlled study recruited 152 traumatic intracerebral hemorrhage patients in our hospital. The observation group (n = 77) received early enteral nutrition intervention (≤ 48 h), while the control group (n = 75) were given delayed enteral nutrition (> 48 h). Further comparison was performed on the recovery of various physiologic functions between the two groups. RESULTS: After treatment, GCS score and GOS score in the observation group were significantly higher than those in the control group (P < 0.05), and mRS Score was significantly lower than that in the control group (P < 0.05). Moreover, the observation group demonstrated a considerable post-treatment elevation in adrenocorticotropic hormone (ACTH) and cortisol (Cor) levels, which were notably higher than the control group's levels (both P < 0.05). The changes in Bifidobacteria, Enterococcus, and Escherichia coli values pre and post-treatment were more remarkable in the observation group (all P < 0.05). Kaplan-Meier survival curve analysis indicated a substantial difference in survival curves between patients who provided with early enteral nutrition and those where it later (P < 0.05). CONCLUSION: The early application of enteral nutrition can promote neurological function recovery, improve the disorder of intestinal flora and the patient's nutritional status, reduce the increase of injury factors under stress, and lower the mortality risk among patients suffering from TICH.

Electric field distributions in realistic 3D rat head models during alternating electric field (AEF) therapy: a computational study.

Objective.Application of alternating electrical fields (AEFs) in the kHz range is an established treatment modality for primary and recurrent glioblastoma. Preclinical studies would enable innovations in treatment monitoring and efficacy, which could then be translated to benefit patients. We present a practical translational process converting image-based data into 3D rat head models for AEF simulations and study its sensitivity to parameter choices.Approach.Five rat head models composed of up to 7 different tissue types were created, and relative permittivity and conductivity of individual tissues obtained from the literature were assigned. Finite element analysis was used to model the AEF strength and distribution in the models with different combinations of head tissues, a virtual tumor, and an electrode pair.Main results.The simulations allowed for a sensitivity analysis of the AEF distribution with respect to different tissue combinations and tissue parameter values.Significance.For a single pair of 5 mm diameter electrodes, an average AEF strength inside the tumor exceeded 1.5 V cm-1, expected to be sufficient for a relevant therapeutic outcome. This study illustrates a robust and flexible approach for simulating AEF in different tissue types, suitable for preclinical studies in rodents and translatable to clinical use.

A new quantitative insight: Interaction of polyethylene microplastics with soil - microbiome - crop.

In this study, the interaction between primary/secondary PE MPs and soil - microbiome - crop complex system and PE MPs enrichment behavior in crops were studied by using the self-developed quantitative characterization method of Eu-MPs and in situ zymography. The results demonstrated for the first time the enrichment effect of micron-sized PE (> 10 µm) in crops, manifested as roots>leaves>stems. Primary PE MPs significantly increased soil TN, TC, SOM and ß-glu activity and inhibited Phos activity. Age-PE MPs significantly reduced soil TN, TP, ß-glu and Phos activities and also have significant inhibitory effects on plant height, stem diameter, and leaf dry weight of maize. Age-PE MPs significantly affected soil microbial diversity, mainly caused by bacterial genera such as UTCFX1, Sphingomonas, Subgroup-6 and Gemmatimonas. Age-PE MPs also affected some metabolism related to microbial community composition and maize growth, including Glycerolipid, Citrate cycle (TCA cycle), C5-Branched dibasic acid, Arginine and proline, Tyrosine metabolism, pentose phosphate pathway, Valine, leucine and isoleucine biosynthesis. These research results indicated that the PE MPs, which are widely present in farmland soils, can affect crop growth, soil microbial community and metabolic function after aging, thus affecting agroecosystems and terrestrial biodiversity.

Review of the advances in lipid anchors-based biosensors for the isolation and detection of exosomes.

Exosomes are nanoparticles with a bilayer lipid structure that carry cargo from their cells of origin. These vesicles are vital to disease diagnosis and therapeutics; however, conventional isolation and detection techniques are generally complicated, time-consuming, and costly, thus hampering the clinical applications of exosomes. Meanwhile, sandwich-structured immunoassays for exosome isolation and detection rely on the specific binding of membrane surface biomarkers, which may be limited by the type and amount of target protein present. Recently, lipid anchors inserted into the membranes of vesicles through hydrophobic interactions have been adopted as a new strategy for extracellular vesicle manipulation. By combining nonspecific and specific binding, the performance of biosensors can be improved variously. This review presents the reaction mechanisms and properties of lipid anchors/probes, as well as advances in the development of biosensors. The combination of signal amplification methods with lipid anchors is discussed in detail to provide insights into the design of convenient and sensitive detection techniques. Finally, the advantages, challenges, and future directions of lipid anchor-based exosome isolation and detection methods are highlighted from the perspectives of research, clinical use, and commercialization.

Scalable fabrication of self-assembled GeSn vertical nanowires for nanophotonic applications.

In this work, scalable fabrication of self-assembled GeSn vertical nanowires (NWs) based on rapid thermal annealing (RTA) and inductively coupled-plasma (ICP) dry etching was proposed. After thermal treatment of molecular-beam-epitaxy-grown GeSn, self-assembled Sn nanodots (NDs) were formed on surface and the spontaneous emission from GeSn direct band was enhanced by ∼5-fold. Employing the self-assembled Sn NDs as template, vertical GeSn NWs with a diameter of 25 ± 6 nm and a density of 2.8 × 109 cm-2 were obtained by Cl-based ICP dry etching technique. A prototype GeSn NW photodetector (PD) with rapid switching ability was demonstrated and the optoelectronic performance of Ge NW PD was systematically studied. The GeSn NW PD exhibited an ultralow dark current density of ∼33 nA/cm2 with a responsivity of 0.245 A/W and a high specific detectivity of 2.40 × 1012 cm Hz1/2 W-1 at 1550 nm under -1 V at 77 K. The results prove that this method is prospective for low-cost and scalable fabrication of GeSn NWs, which are promising for near infrared or short wavelength infrared nanophotonic devices.

Current status of the preclinical evaluation of alternating electric fields as a form of cancer therapy.

Exposing cancer cells to alternating electric fields of 100-300 kHz frequency and 1-4 V/cm strength has been shown to significantly reduce cancer growth in cell culture and in human patients. This form of anti-cancer therapy is more commonly referred to as tumor treating fields (TTFields), a novel treatment modality that has been approved by the U.S. Food and Drug Administration for use in patients with glioblastoma and malignant pleural mesothelioma. Pivotal trials in other solid organ cancer trials are underway. In regards to overall survival, TTFields alone is comparable to chemotherapy alone in recurrent glioblastoma. However, when combined with adjuvant chemotherapy, TTFields prolong median survival by 4.9 months in newly-diagnosed glioblastoma. TTFields hold promise as a therapeutic approach to numerous solid organ cancers. This review summarizes the current status of TTFields research at the preclinical level, highlighting recent aspects of a relatively complex working hypothesis. In addition, we point out the gaps between limited preclinical in vivo studies and the available clinical data. To date, no customized system for TTFields delivery in rodent models of glioblastoma has been presented. We aim to motivate the expansion of TTFields preclinical research and facilitate the availability of suitable hardware, to ultimately improve outcomes in patients with cancer.

Efficacy and safety of tirzepatide in patients with type 2 diabetes: A systematic review and meta-analysis.

Purpose: A systematic review and meta-analysis was conducted to combine the data available from clinical trials and evaluate the clinical efficacy and safety of tirzepatide in people with type 2 diabetes (T2D). Methods: We systematically searched the MEDLINE, Embase, Cochrane Library, and clinical trials registries (https://clinicaltrials.gov) up to 25 March 2022 for randomized controlled trials (RCTs) that compared tirzepatide with placebo or active hypoglycemic drugs in subjects with T2D. Heterogeneity was judged by the I 2 value and Cochran's Q test. The randomized effects model was adopted to calculate risk ratios and weighted mean differences (WMDs). The primary outcome was the change from baseline in HbA1c levels. Secondary efficacy endpoints were fasting serum glucose (FSG), change of body weight, blood pressure, fasting lipid profiles, and safety indexes. Results: Six trials comprising 6,579 subjects (4,410 in the tirzepatide group and 2,054 in the control group) fulfilled the pre-specified criteria and were included in the study. Tirzepatide treatment resulted in reducing HbA1c (WMD: -1.07%; 95% confidence intervals [CIs]: -1.44, -0.56), FSG (WMD, -21.50 mg/dl; 95% CI: -34.44, -8.56), body weight (WMD: -7.99 kg; 95% CI -11.36, -4.62), and blood pressure and ameliorated fasting lipid profiles, without increasing hypoglycemia, either as monotherapy or an add-on therapy. Tirzepatide increased the risk of gastrointestinal adverse events mainly in add-on therapy but not in terms of pancreatitis or cholelithiasis. Furthermore, tirzepatide presented a dose-response effect on the reduction in HbA1c and body weight and increase in nausea and vomiting. Conclusion: In patients with type 2 diabetes, tirzepatide shows superior blood glucose control and weight loss performance, without an increased risk of hypoglycemia. Systematic Review Registration: (https://www.crd.york.ac.uk/PROSPERO), identifier (CRD42022319442).

'Stress hyperglycemia ratio and in-hospital prognosis in non-surgical patients with heart failure and type 2 diabetes.

OBJECTIVE: To evaluate the impact of stress hyperglycemia on the in-hospital prognosis in non-surgical patients with heart failure and type 2 diabetes. RESEARCH DESIGN AND METHODS: We identified non-surgical hospitalized patients with heart failure and type 2 diabetes from a large electronic medical record-based database of diabetes in China (WECODe) from 2011 to 2019. We estimated stress hyperglycemia using the stress hyperglycemia ratio (SHR) and its equation, say admission blood glucose/[(28.7 × HbA1c)- 46.7]. The primary outcomes included the composite cardiac events (combination of death during hospitalization, requiring cardiopulmonary resuscitation, cardiogenic shock, and the new episode of acute heart failure during hospitalization), major acute kidney injury (AKI stage 2 or 3), and major systemic infection. RESULTS: Of 2875 eligible Chinese adults, SHR showed U-shaped associations with composite cardiac events, major AKI, and major systemic infection. People with SHR in the third tertile (vs those with SHR in the second tertile) presented higher risks of composite cardiac events ([odds ratio, 95% confidence interval] 1.89, 1.26 to 2.87) and major AKI (1.86, 1.01 to 3.54). In patients with impaired kidney function at baseline, both SHR in the first and third tertiles anticipated higher risks of major AKI and major systemic infection. CONCLUSIONS: Both high and low SHR indicates poor prognosis during hospitalization in non-surgical patients with heart failure and type 2 diabetes.

Causal relationships between metabolic-associated fatty liver disease and iron status: Two-sample Mendelian randomization.

BACKGROUND & AIMS: Dysregulated iron homeostasis plays an important role in the hepatic manifestation of metabolic-associated fatty liver disease (MAFLD). We investigated the causal effects of five iron metabolism markers, regular iron supplementation and MAFLD risk. METHODS: Genetic summary statistics were obtained from open genome-wide association study databases. Two-sample bidirectional Mendelian randomization analysis was performed to estimate the causal effect between iron status and MAFLD, including Mendelian randomization inverse-variance weighted, weighted median methods and Mendelian randomization-Egger regression. The Mendelian randomization-PRESSO outlier test, Cochran's Q test and Mendelian randomization-Egger regression were used to assess outliers, heterogeneity and pleiotropy respectively. RESULTS: Mendelian randomization inverse-variance weighted results showed that the genetically predicted per standard deviation increase in liver iron (Data set 2: odds ratio 1.193, 95% confidence interval [CI] 1.074-1.326, p = .001) was associated with an increased MAFLD risk, consistent with the weighted median estimates and Mendelian randomization-Egger regression, although Data set 1 was not significant. Mendelian randomization inverse-variance weighted analysis showed that genetically predicted MAFLD was significantly associated with increased serum ferritin levels in both datasets (Dataset 1: ß = .038, 95% CI = .014 to .062, p = .002; Dataset 2: ß = .081, 95% CI = .025 to .136, p = .004), and a similar result was observed with the weighted median methods for Dataset 2 instead of Mendelian randomization-Egger regression. CONCLUSIONS: This study uncovered genetically predicted causal associations between iron metabolism status and MAFLD. These findings underscore the need for improved guidelines for managing MAFLD risk by emphasizing hepatic iron levels as a risk factor and ferritin levels as a prognostic factor.

Scaling behavior of InAlN/GaN HEMTs on silicon for RF applications.

Due to the low cost and the scaling capability of Si substrate, InAlN/GaN high-electron-mobility transistors (HEMTs) on silicon substrate have attracted more and more attentions. In this paper, a high-performance 50-nm-gate-length InAlN/GaN HEMT on Si with a high on/off current (Ion/Ioff) ratio of 7.28 × 106, an average subthreshold swing (SS) of 72 mV/dec, a low drain-induced barrier lowing (DIBL) of 88 mV, an off-state three-terminal breakdown voltage (BVds) of 36 V, a current/power gain cutoff frequency (fT/fmax) of 140/215 GHz, and a Johnson's figure-of-merit (JFOM) of 5.04 THz V is simultaneously demonstrated. The device extrinsic and intrinsic parameters are extracted using equivalent circuit model, which is verified by the good agreement between simulated and measured S-parameter values. Then the scaling behavior of InAlN/GaN HEMTs on Si is predicted using the extracted extrinsic and intrinsic parameters of devices with different gate lengths (Lg). It presents that a fT/fmax of 230/327 GHz can be achieved when Lg scales down to 20 nm with the technology developed in the study, and an improved fT/fmax of 320/535 GHz can be achieved on a 20-nm-gate-length InAlN/GaN HEMT with regrown ohmic contact technology and 30% decreased parasitic capacitance. This study confirms the feasibility of further improvement of InAlN/GaN HEMTs on Si for RF applications.