Screening for metabolic dysfunction-associated fatty liver disease: Time to discard the emperor's clothes of normal liver enzymes?

Metabolic dysfunction-associated fatty liver disease (MAFLD) is the most prevalent chronic liver condition worldwide. Current liver enzyme-based screening methods have limitations that may missed diagnoses and treatment delays. Regarding Chen et al, the risk of developing MAFLD remains elevated even when alanine aminotransferase levels fall within the normal range. Therefore, there is an urgent need for advanced diagnostic techniques and updated algorithms to enhance the accuracy of MAFLD diagnosis and enable early intervention. This paper proposes two potential screening methods for identifying individuals who may be at risk of developing MAFLD: Lowering these thresholds and promoting the use of noninvasive liver fibrosis scores.

Serum bile acid profiles are associated with heart failure with preserved ejection fraction in patients with metabolic dysfunction-associated fatty liver disease: An exploratory study.

AIM: To analyse the association between serum bile acid (BA) profile and heart failure (HF) with preserved ejection fraction (HFpEF) in patients with metabolic dysfunction-associated fatty liver disease (MAFLD). METHODS: We enrolled 163 individuals with biopsy-proven MAFLD undergoing transthoracic echocardiography for any indication. HFpEF was defined as left ventricular ejection fraction >50% with at least one echocardiographic feature of HF (left ventricular diastolic dysfunction, abnormal left atrial size) and at least one HF sign or symptom. Serum levels of 38 BAs were analysed using ultra-performance liquid chromatography coupled with tandem mass spectrometry. RESULTS: Among the 163 patients enrolled (mean age 47.0 ± 12.8 years, 39.3% female), 52 (31.9%) and 43 (26.4%) met the HFpEF and pre-HFpEF criteria, and 38 serum BAs were detected. Serum ursodeoxycholic acid (UDCA) and hyocholic acid (HCA) species were lower in patients with HFpEF and achieved statistical significance after correction for multiple comparisons. Furthermore, decreases in glycoursodeoxycholic acid and tauroursodeoxycholic acid were associated with HF status. CONCLUSIONS: In this exploratory study, specific UDCA and HCA species were associated with HFpEF status in adults with biopsy-confirmed MAFLD.

Quantifying Microstructure Features for High-Performance Solid Oxide Cells.

The drive for sustainable energy solutions has spurred interest in solid oxide fuel cells (SOFCs). This study investigates the impact of sintering temperature on SOFC anode microstructures using advanced 3D focused ion beam-scanning electron microscopy (FIB-SEM). The anode's ceramic-metal composition significantly influences electrochemical performance, making optimization crucial. Comparing cells sintered at different temperatures reveals that a lower sintering temperature enhances yttria-stabilized zirconia (YSZ) and nickel distribution, volume, and particle size, along with the triple-phase boundary (TPB) interface. Three-dimensional reconstructions illustrate that the cell sintered at a lower temperature exhibits a well-defined pore network, leading to increased TPB density. Hydrogen flow simulations demonstrate comparable permeability for both cells. Electrochemical characterization confirms the superior performance of the cell sintered at the lower temperature, displaying higher power density and lower total cell resistance. This FIB-SEM methodology provides precise insights into the microstructure-performance relationship, eliminating the need for hypothetical structures and enhancing our understanding of SOFC behavior under different fabrication conditions.

Myocardial infarction accelerates the progression of MASH by triggering immunoinflammatory response and induction of periosti.

Patients with metabolic dysfunction-associated steatotic liver disease (MASLD), especially advanced metabolic dysfunction-associated steatohepatitis (MASH), have an increased risk of cardiovascular diseases (CVDs). Whether CVD events will, in turn, influence the pathogenesis of MASLD remains unknown. Here, we show that myocardial infarction (MI) accelerates hepatic pathological progression of MASLD. Patients with MASLD who experience CVD events after their diagnosis exhibit accelerated liver fibrosis progression. MI promotes hepatic fibrosis in mice with MASH, accompanied by elevated circulating Ly6Chi monocytes and their recruitment to damaged liver tissues. These adverse effects are significantly abrogated when deleting these cells. Meanwhile, MI substantially increases circulating and cardiac periostin levels, which act on hepatocytes and stellate cells to promote hepatic lipid accumulation and fibrosis, finally exacerbating hepatic pathological progression of MASH. These preclinical and clinical results demonstrate that MI alters systemic homeostasis and upregulates pro-fibrotic factor production, triggering cross-disease communication that accelerates hepatic pathological progression of MASLD.

Causal relationship between primary biliary cholangitis and inflammatory bowel disease: a Mendelian randomization study.

Background: Several studies indicated that inflammatory bowel disease (IBD) may contribute to increased susceptibility to primary biliary cholangitis (PBC). However, the causal relationship between IBD and PBC remains unclear. Methods: The genetic variant data of patients with IBD and PBC were obtained from published genome-wide association studies (GWASs). The IBD data were further divided into a discovery dataset and a validation dataset depending on the data source. We conducted a two-sample Mendelian randomization (MR) analysis using the inverse variance weighting (IVW), MR-Egger, weighted median (WM), MR robust adjusted profile score (MR-RAPS), and maximum likelihood (ML) methods, with IVW being the main focus, to verify the causal relationship between IBD and PBC. Additionally, a series of sensitivity analyses were performed to ensure the reliability of the results. Results: In the discovery cohort, the IVW analysis results (OR = 1.114, P = 0.011) indicated a significant association between IBD and PBC. The MR-RAPS (OR = 1.130, P = 0.007) and ML (OR = 1.115, P = 0.011) analyses yielded results consistent with those of IVW in confirming IBD as a risk factor for PBC. In the validation cohort, consistent findings were observed regarding the causal relationship between IBD and PBC using IVW, MR-RAPS, and ML analyses; all three methods identified IBD as a risk factor for developing PBC. By the IVW analysis, Crohn's disease (CD) emerged as the most prominent subtype of IBD associated with an increased risk of developing PBC in both the discovery cohort (OR = 1.068, P = 0.049) and the validation cohort (OR = 1.082, P = 0.019). Conclusion: The results of the MR analysis suggest a causal relationship between IBD and PBC, highlighting the necessity for proactive PBC prevention in patients with IBD, particularly those with CD.

High-Energy Laser Protection Performance of Fibrous Felt-Reinforced Aerogels with Hierarchical Porous Architectures.

Continuous-wave lasers can cause irreversible damage to structured materials in a very short time. Modern high-energy laser protection materials are mainly constructed from ceramic, polymer, and metal constitutions. However, these materials are protected by sacrificing their structural integrity under the irradiation of high-energy lasers. In this contribution, we reported multilayer fibrous felt-reinforced aerogels that can sustain the continuous irradiation of a laser at a power density of 120 MW·m-2 without structural damage. It is found that the exceptional high-energy laser protection performance and the comparable mechanical properties of aerogel nanocomposites are attributed to the unique characteristics of hierarchical porous architectures. In comparison with various preparation methods and other aerogel materials, multilayer fibrous felt-reinforced aerogels exhibit the best performance in high-energy laser protection, arising from the gradual interception and the Raman-Rayleigh scattering cycles of a high-energy laser in the porous aerogels. Furthermore, a near-zero thermal expansion coefficient and extremely low thermal conductivity at high temperature allow the lightweight felt-reinforced aerogels to be applied in extreme conditions. The felt-reinforced aerogels reported herein offer an attractive material that can withstand complex thermomechanical stress and retain excellent insulation properties at extremely high temperature.

Effect of exogenous calcitriol on myopia development and axial length in guinea pigs with form deprivation myopia.

The annual increase in myopia prevalence poses a significant economic and health challenge. Our study investigated the effect of calcitriol role in myopia by inducing the condition in guinea pigs through form deprivation for four weeks. Untargeted metabolomics methods were used to analyze the differences in metabolites in the vitreous body, and the expression of vitamin D receptor (VDR) in the retina was detected. Following form deprivation, the guinea pigs received intraperitoneal injections of calcitriol at different concentrations. We assessed myopia progression using diopter measurements and biometric analysis after four weeks. Results indicated that form deprivation led to a pronounced shift towards myopia, characterized by reduced choroidal and scleral thickness, disorganized collagen fibers, and decreased scleral collagen fiber diameter. Notably, a reduction in calcitriol expression in vitreous body, diminished vitamin D and calcitriol levels in the blood, and decreased VDR protein expression in retinal tissues were observed in myopic guinea pigs. Calcitriol administration effectively slowed myopia progression, preserved choroidal and scleral thickness, and prevented the reduction of scleral collagen fiber diameter. Our findings highlight a significant decrease in calcitriol and VDR expressions in myopic guinea pigs and demonstrate that exogenous calcitriol supplementation can halt myopia development, enhancing choroidal and scleral thickness and scleral collagen fiber diameter.

Adaptive Fabrication of Electrochemical Chips with a Paste-Dispensing 3D Printer.

Electrochemical (EC) detection is a powerful tool supporting simple, low-cost, and rapid analysis. Although screen printing is commonly used to mass fabricate disposable EC chips, its mask is relatively expensive. In this research, we demonstrated a method for fabricating three-electrode EC chips using 3D printing of relatively high-viscosity paste. The electrodes consisted of two layers, with carbon paste printed over silver/silver chloride paste, and the printed EC chips were baked at 70 °C for 1 h. Engineering challenges such as bulging of the tubing, clogging of the nozzle, dripping, and local accumulation of paste were solved by material selection for the tube and nozzle, and process optimization in 3D printing. The EC chips demonstrated good reversibility in redox reactions through cyclic voltammetry tests, and reliably detected heavy metal ions Pb(II) and Cd(II) in solutions using differential pulse anodic stripping voltammetry measurements. The results indicate that by optimizing the 3D printing of paste, EC chips can be obtained by maskless and flexible 3D printing techniques in lieu of screen printing.

Obesity Paradox in Patients with Acute Coronary Syndrome: Is Malnutrition the Answer?

BACKGROUND: Obesity paradox has been reported in patients with cardiovascular disease, showing an inverse association between obesity as defined by BMI (in kg/m2) and prognosis. Nutritional status is associated with systemic inflammatory response and affects cardiovascular disease outcomes. OBJECTIVES: This study sought to examine the influence of obesity and malnutrition on the prognosis of patients with acute coronary syndrome (ACS). METHODS: This study included consecutive patients diagnosed with ACS and underwent coronary angiogram between January 2009 and February 2023. At baseline, patients were categorized according to their BMI as follows: underweight (<18), normal weight (18-24.9), overweight (25.0-29.9), and obese (>30.0). We assessed the nutritional status by Prognostic Nutritional Index (PNI). Malnutrition was defined as a PNI value of <38. RESULTS: Of the 21,651 patients with ACS, 582 (2.7%) deaths from any cause were observed over 28.7 months. Compared with the patient's state of normal weight, overweight, and obesity were associated with decreased risk of all-cause mortality. Malnutrition was independently associated with poor survival (hazards ratio: 2.64; 95% CI: 2.24, 3.12; P < 0.001). In malnourished patients, overweight and obesity showed a 39% and 72% reduction in the incidence of all-cause mortality, respectively. However, in nourished patients, no significant reduction in the incidence of all-cause mortality was observed (all P > 0.05). CONCLUSIONS: Obesity paradox appears to occur in patients with ACS. Malnutrition may be a significant independent risk factor for prognosis in patients with ACS. The obesity paradox is influenced by the status of malnutrition.

High-Density Dynamic Bonds Cross-Linked Hydrogel with Tissue Adhesion, Highly Efficient Self-Healing Behavior, and NIR Photothermal Antibacterial Ability as Dressing for Wound Repair.

Multifunctional hydrogels with tissue adhesion, self-healing behavior, and antibacterial properties have potential in wound healing applications. However, their inefficient self-healing behavior and antibacterial agents can cause long-term cytotoxicity and drug resistance, considerably limiting their clinical use. Herein, we reported a PDA@LA hydrogel constructed by introducing polydopamine nanoparticles (PDA-NPs) into a high-density dynamic bonds cross-linked lipoic acid (LA) hydrogel that was formed by the polymerization of LA. Because of its rich carboxyl groups, the LA hydrogel could adhere firmly to various tissues. Owing to the high-density dynamic bonds, the cut LA hydrogel exhibited highly inefficient self-healing behavior and recovered to its uncut state after self-healing for 10 min. After the introduction of the PDA-NPs, the hydrogel was able to heat up to more than 40 °C to kill approximately 100% of the Escherichia coli and Staphylococcus aureus under near-infrared (NIR) laser, thus resisting wound infections. Because no toxic antibacterial agent was used, the PDA@LA hydrogel caused mild long-term cytotoxicity or drug resistance. Consequently, the adhesive, highly efficient self-healing, and NIR photothermal antibacterial PDA@LA hydrogel exhibits considerable potential for clinical use.

Mechanistic Insights into Surfactant-Modulated Electrode-Electrolyte Interface for Steering H2O2 Electrosynthesis.

Electrocatalytic reactions taking place at the electrified electrode-electrolyte interface involve processes of proton-coupled electron transfer. Interfacial protons are delivered to the electrode surface via a H2O-dominated hydrogen-bond network. Less efforts are made to regulate the interfacial proton transfer from the perspective of interfacial hydrogen-bond network. Here, we present quaternary ammonium salt cationic surfactants as electrolyte additives for enhancing the H2O2 selectivity of the oxygen reduction reaction (ORR). Through in situ vibrational spectroscopy and molecular dynamics calculation, it is revealed that the surfactants are irreversibly adsorbed on the electrode surface in response to a given bias potential range, leading to the weakening of the interfacial hydrogen-bond network. This decreases interfacial proton transfer kinetics, particularly at high bias potentials, thus suppressing the 4-electron ORR pathway and achieving a highly selective 2-electron pathway toward H2O2. These results highlight the opportunity for steering H2O-involved electrochemical reactions via modulating the interfacial hydrogen-bond network.

Rate-Pressure Product is a Novel Predictor for Short- and Long-Term Mortality in Patients with Acute Coronary Syndrome Undergoing Primary PCI/Immediate Invasive Strategy.

Background: Rate-pressure product (RPP) calculated by multiplying heart rate by systolic blood pressure, is a convenient indicator closely associated with cardiac work or myocardial oxygen consumption. It has been reported to relate strongly to important indices of cardiovascular risk in patients with myocardial ischemia. However, its relationship with short- and long-term mortality in patients with acute coronary syndrome (ACS) undergoing primary PCI/immediate invasive strategy has not been defined. Methods: This study analyzed 1301 consecutive ACS patients who had undergone primary PCI, between January 2018 and September 2021. Patients with systolic BP < 90 mmHg were excluded to avoid the confounding effect of cardiogenic shock. RPP values were collected on admission and were divided into four groups: RPP ≤ 7.4, 7.4 ≤ 8.8, 8.8 <8.8 < RPP8, and RPP > 10.8. Clinical endpoints were in-hospital cardiac and long-term all-cause mortality. The predictive performance was assessed by C-statistic, multivariate analysis and survival analysis. Results: Multivariate analysis showed that these in the highest vs lowest category of RPP (>10.8 vs ≤7.4) had OR of 4.33 (95% CI=1.10 -17.01; P = 0.036) in in-hospital cardiac mortality and 3.15 (95% CI=1.24 -8.00; P = 0.016) in long-term all-cause mortality. In C-statistic analyses, RPP was a strong predictor in ACS, STEMI or UA/NSTEMI group for in-hospital cardiac mortality (AUC = 0.746, 95% CI = 0.722-0.770, p < 0.001) and long-term all-cause mortality (AUC = 0.701, 95% CI = 0.675-0.725, p < 0.001). The Kaplan-Meier event rate for long-term survival of RPP > 10.8 was significantly lower than that of RPP ≤ 10.8. Conclusion: RPP showed a positive association with in-hospital cardiac or long-term all-cause mortality in ACS patients undergoing primary PCI/immediate invasive strategy, and RPP > 10.8 can be as an independent predictor.

Layer Control of Magneto-Optical Effects and Their Quantization in Spin-Valley Splitting Antiferromagnets.

Magneto-optical effects (MOE), interfacing the fundamental interplay between magnetism and light, have served as a powerful probe for magnetic order, band topology, and valley index. Here, based on multiferroic and topological bilayer antiferromagnets (AFMs), we propose a layer control of MOE (L-MOE), which is created and annihilated by layer-stacking or an electric field effect. The key character of L-MOE is the sign-reversible response controlled by ferroelectric polarization, the Néel vector, or the electric field direction. Moreover, the sign-reversible L-MOE can be quantized in topologically insulating AFMs. We reveal that the switchable L-MOE originates from the combined contributions of spin-conserving and spin-flip interband transitions in spin-valley splitting AFMs, a phenomenon not observed in conventional AFMs. Our findings bridge the ancient MOE to the emergent realms of layertronics, valleytronics, and multiferroics and may hold immense potential in these fields.

Crystal Thermal Transport in Altermagnetic RuO_{2}.

We demonstrate the emergence of a pronounced thermal transport in the recently discovered class of magnetic materials-altermagnets. From symmetry arguments and first-principles calculations performed for the showcase altermagnet, RuO_{2}, we uncover that crystal Nernst and crystal thermal Hall effects in this material are very large and strongly anisotropic with respect to the Néel vector. We find the large crystal thermal transport to originate from three sources of Berry's curvature in momentum space: the Weyl fermions due to crossings between well-separated bands, the strong spin-flip pseudonodal surfaces, and the weak spin-flip ladder transitions, defined by transitions among very weakly spin-split states of similar dispersion crossing the Fermi surface. Moreover, we reveal that the anomalous thermal and electrical transport coefficients in RuO_{2} are linked by an extended Wiedemann-Franz law in a temperature range much wider than expected for conventional magnets. Our results suggest that altermagnets may assume a leading role in realizing concepts in spin caloritronics not achievable with ferromagnets or antiferromagnets.