Parametric Control via the Algebraic Expression of Lotus-Type Pore Shapes in Metals.

Lotus-type porous metals, characterized by low densities, large surface areas, and directional properties, are contemporarily utilized as lightweight, catalytic, and energy-damping materials; heat sinks; etc. In this study, the effects of dimensionless working parameters on the morphology of lotus-type pores in metals during unidirectional solidification were extensively investigated via general algebraic expressions. The independent dimensionless parameters include metallurgical, transport, and geometrical parameters such as Sieverts' law constant, a partition coefficient, the solidification rate, a mass transfer coefficient, the imposed mole fraction of a solute gas, the total pressure at the top free surface, hydrostatic pressure, a solute transport parameter, inter-pore spacing, and initial contact angle. This model accounts for transient gas pressure in the pore, affected by the solute transfer, gas, capillary, and hydrostatic pressures, and Sieverts' laws at the bubble cap and top free surface. Solute transport across the cap accounts for solute convection at the cap and the amount of solute rejected by the solidification front into the pore. The shape of lotus-type pores can be described using a proposed fifth-degree polynomial approximation, which captures the major portions between the initial contact angle and the maximum radius at a contact angle of 90 degrees, obtained by conserving the total solute content in the system. The proposed polynomial approximation, along with its working parameters, offers profound insights into the formation and shape of lotus-type pores in metals. It systematically provides deep insights into mechanisms that may not be easily revealed with experimental studies. The prediction of a lotus-type pore shape is thus algebraically achieved in good agreement with the available experimental data and previous analytical results.

Skin sympathetic nerve activity in symptomatic and asymptomatic paroxysmal atrial fibrillation.

BACKGROUND: It remains unclear what causes symptoms in patients with paroxysmal atrial fibrillation (AF). OBJECTIVE: This study aimed to correlate the magnitudes of the skin sympathetic nerve activity (SKNA) with symptoms in patients with AF. METHODS: We prospectively enrolled patients with symptomatic paroxysmal AF for ambulatory electrocardiogram and SKNA recording. Heart rhythms at time of symptoms were categorized as AF or normal sinus rhythm (NSR). Maximal and average SKNA (aSKNA) and heart rate (HR) were compared between symptomatic and asymptomatic AF and NSR episodes using mixed effects models to account for within-patient correlations. RESULTS: Among the 31 enrolled patients, 16 (52%) had at least one episode of AF, and 24 (77%) endorsed symptoms during the monitoring period. Compared with asymptomatic AF episodes, symptomatic AF episodes had higher maximal aSKNA (1.260 [IQR 1.114-1.723] µV vs. 1.108 [IQR 0.974-1.312] µV, p<0.001) and higher maximal HR (152±24 bpm vs. 132±19 bpm, p<0.001). Symptomatic NSR episodes were associated with higher maximal aSKNA (1.612 [IQR 1.287-2.027] µV vs. 1.332 [IQR 1.033-1.668] µV, p=0.001) and higher maximal HR (152±24 bpm vs. 105±16 bpm, p<0.001) than asymptomatic NSR episodes. Of the symptomatic episodes, 66 (73%) occurred during NSR and 24 (27%) during AF. All p-values were obtained from mixed effects models. CONCLUSION: Symptomatic episodes in patients with paroxysmal AF were more frequently associated with NSR than AF. Symptomatic AF and NSR episodes were associated with higher aSKNA than asymptomatic episodes. In patients with paroxysmal AF, symptoms correlate better with SKNA than heart rhythm.

pH-Responsive ß-Glucans-Complexed mRNA in LNPs as an Oral Vaccine for Enhancing Cancer Immunotherapy.

mRNA vaccines for cancer immunotherapy are commonly delivered using lipid nanoparticles (LNPs), which, when administered intravenously, may accumulate in the liver, potentially limiting their therapeutic efficacy. To overcome this challenge, the study introduces an oral mRNA vaccine formulation tailored for efficient uptake by immune cells in the gastrointestinal (GI) tract, known for its high concentration of immune cells, including dendritic cells (DCs). This formulation comprises mRNA complexed with ß-glucans (ßGlus), a potential adjuvant for vaccines, encapsulated within LNPs (ßGlus/mRNA@LNPs). The ßGlus/mRNA complexes within the small compartments of LNPs demonstrate a distinctive ability to partially dissociate and reassociate, responding to pH changes, effectively shielding mRNA from degradation in the harsh GI environment. Upon oral administration to tumor-bearing mice, ßGlus/mRNA@LNPs are effectively taken up by intestinal DCs and local nonimmune cells, bypassing potential liver accumulation. This initiates antigen-specific immune responses through successful mRNA translation, followed by drainage into the mesenteric lymph nodes to stimulate T cells and trigger specific adaptive immune responses, ultimately enhancing antitumor effects. Importantly, the vaccine demonstrates safety, with no significant inflammatory reactions observed. In conclusion, the potential of oral ßGlus/mRNA@LNPs delivery presents a promising avenue in cancer immunotherapy, offering needle-free and user-friendly administration for widespread adoption and self-administration.

Sympathetic toggled paroxysmal atrial fibrillation and recurrent premature atrial contractions in ambulatory patients.

BACKGROUND: Autonomic nerve activity is important in the mechanisms of paroxysmal atrial fibrillation (PAF). OBJECTIVE: The purpose of this study was to test the hypothesis that a single burst of skin sympathetic nerve activity (SKNA) can toggle on and off PAF or premature atrial contraction (PAC) clusters. METHODS: Simultaneous recording of SKNA and electrocardiogram (neuECG) recording was performed over 7 days in patients with PAF. RESULTS: In study 1, 8 patients (7 men and 1 woman; age 62 ± 8 years) had 124 episodes of PAF. An SKNA burst toggled both on and off PAF in 8 episodes (6.5%) (type 1), toggled on but not off in 12 episodes (9.7%) (type 2), and toggled on a PAC cluster followed by PAF in 4 episodes (3.2%) (type 3). The duration of these PAF episodes was <10 minutes. The remaining 100 episodes (80.6%) were associated with active SKNA bursts throughout PAF (type 4) and lasted longer than type 1 (P = .0185) and type 2 (P = .0027) PAF. There were 47 PAC clusters. Among them, 24 (51.1%) were toggled on and off, and 23 (48.9%) were toggled on but not off by an SKNA burst. In study 2, 17 patients (9 men and 8 women; age 58 ± 12 years) had <10 minutes of PAF (4, 8, 0, and 31 of types 1, 2, 3, and 4, respectively). There were significant circadian variations of all types of PAF. CONCLUSION: A single SKNA burst can toggle short-duration PAF and PAC cluster episodes on and off. The absence of continued SKNA after the onset might have affected the maintenance of these arrhythmias.

Sustainability of exercise-induced benefits on circulating MicroRNAs and physical fitness in community-dwelling older adults: a randomized controlled trial with follow up.

BACKGROUND: Circulating miRNAs (c-miR) have been shown to be potential biomarkers in sarcopenia, but the miRNAs response to aerobic exercise in older people remains inconclusive. We sought to examine the exercise benefits on physical fitness and miRNAs, and to explore the mediating effect of miRNAs on training-induced fitness changes. METHODS: This controlled trial recruited 58 community-dwelling older adults and randomized them into exercise group (EX) and control group (CON). EX received 8-week supervised moderate intensity cycling training 3x/week. C-miR expression (c-miR-21, c-miR-126, c-miR-146a, c-miR-222), physical fitness (body composition, cardiorespiratory fitness, muscular fitness) and physical activity level (PAL, measured as in daily step counts) were evaluated at baseline, post-training, and post-16-week follow-up. The mediating effect of miRNA expression onto exercise-induced physical fitness change was determined by causal mediation analysis (CMA). RESULTS: Exercise significantly improved body fat and cardiorespiratory fitness in older people while maintaining muscle mass and strength, and augmented expression of c-miR-126, c-miR-146a, and c-miR-222 for up to 16 weeks post-training. Notably, older people in EX had substantially higher daily step counts than CON throughout the study even after the active training period. However, CMA revealed no significant indirect effect but a potential mediating effect of c-miR-21, but not the rest, onto the body composition, cardiorespiratory fitness, and lower limb strength. CONCLUSION: An eight-week supervised MICT program promoted a higher level of physical activity up to 16 weeks post-training, which induces better cardiorespiratory fitness and resists decline in muscular measures. C-miRNA, especially c-miR-21, potentially mediates the training effect upon fitness.

Deep learning evaluation of echocardiograms to identify occult atrial fibrillation.

Atrial fibrillation (AF) often escapes detection, given its frequent paroxysmal and asymptomatic presentation. Deep learning of transthoracic echocardiograms (TTEs), which have structural information, could help identify occult AF. We created a two-stage deep learning algorithm using a video-based convolutional neural network model that (1) distinguished whether TTEs were in sinus rhythm or AF and then (2) predicted which of the TTEs in sinus rhythm were in patients who had experienced AF within 90 days. Our model, trained on 111,319 TTE videos, distinguished TTEs in AF from those in sinus rhythm with high accuracy in a held-out test cohort (AUC 0.96 (0.95-0.96), AUPRC 0.91 (0.90-0.92)). Among TTEs in sinus rhythm, the model predicted the presence of concurrent paroxysmal AF (AUC 0.74 (0.71-0.77), AUPRC 0.19 (0.16-0.23)). Model discrimination remained similar in an external cohort of 10,203 TTEs (AUC of 0.69 (0.67-0.70), AUPRC 0.34 (0.31-0.36)). Performance held across patients who were women (AUC 0.76 (0.72-0.81)), older than 65 years (0.73 (0.69-0.76)), or had a CHA2DS2VASc ≥2 (0.73 (0.79-0.77)). The model performed better than using clinical risk factors (AUC 0.64 (0.62-0.67)), TTE measurements (0.64 (0.62-0.67)), left atrial size (0.63 (0.62-0.64)), or CHA2DS2VASc (0.61 (0.60-0.62)). An ensemble model in a cohort subset combining the TTE model with an electrocardiogram (ECGs) deep learning model performed better than using the ECG model alone (AUC 0.81 vs. 0.79, p = 0.01). Deep learning using TTEs can predict patients with active or occult AF and could be used for opportunistic AF screening that could lead to earlier treatment.

Comparison of the effect between traditional conservation and nasointestinal tube placement in adhesive small bowel obstruction: A matched case-control study.

Adhesive small bowel obstruction (ASBO) causes a major burden in emergency medicine. Owing to in situ decompression, nasointestinal tube (NIT) placement has been increasingly used in clinical practice compared with traditional conservation (TC); however, the indications remain controversial. This study was designed to explore the indications for each treatment in ASBOs and then suggest the optimal strategy. After propensity score matching, 128 pairs were included (the NIT and TC groups). The occurrence of severe adverse events (SAEs), peri-treatment clinical parameters, and radiological features were compared between the successful and failed treatment groups. According to different stages of the entire treatment, the independent risk factors for adverse effects for ASBO were analysed in phase I and phase II. In phase I, normal red blood cells (RBC) levels (p = 0.011) and a balanced sodium ion level (p = 0.016) positively affected the outcomes of TC treatment. In phase II, for the TC group, the successful treatment rate reached 79.5% for patients with ASBOs whose normal RBC levels (p = 0.006) or decreasing white blood cells (WBC) levels (p = 0.014) after treatment. For the NIT group, the treatment success rate was 68.1% for patients whose electrolyte imbalance could be reversed or whose neutrophil count/lymphocyte ratio (NLR) levels was lower than 4.3 (p = 0.018). TC treatment is highly recommended for patients with normal RBC counts and sodium levels pretreatment. After dynamic monitoring of the treatment process, for both the TC and NIT groups, once ASBOs had elevated inflammatory biomarkers or irreversible electrolyte disturbances, surgical interference was preferred.

(E,Z)-1,1,1,4,4,4-Hexafluorobut-2-enes: hydrofluoroolefins halogenation/dehydrohalogenation cascade to reach new fluorinated allene.

A series of 2,3-dihalo-1,1,1,4,4,4-hexafluorobutanes and 2-halo-1,1,1,4,4,4-hexafluorobut-2-enes were prepared from commercially available hydrofluoroolefins 1,1,1,4,4,4-hexafluorobut-2-enes and their 1H, 19F and 13C chemical shifts measured. Some reactions of synthesized 2-halo-1,1,1,4,4,4-hexafluorobut-2-enes have been investigated. A simple, one-pot procedure for the preparation of a new allene (1,1,4,4,4-pentafluorobuta-1,2-diene) and some of its transformations is presented.

Associations of maternal serum concentration of iron-related indicators with birth outcomes in Chinese: a pilot prospective cohort study.

BACKGROUND: Previous studies of maternal iron and birth outcomes have been limited to single indicators that do not reflect the comprehensive relationship with birth outcomes. We aimed to investigate the relationship between maternal iron metabolism and neonatal anthropometric indicators using comprehensive iron-related indicators. METHODS: A total of 914 Chinese mother-child dyads were enrolled in this prospective study. Subjects' blood samples were collected at ≤ 14 weeks of gestation. Serum concentrations of iron-related indicators were measured by enzyme-linked immunosorbent assay (ELISA). Femur length was measured by B-ultrasound nearest delivery. Neonatal anthropometric indicators were collected from medical records. RESULTS: After adjustment for potential covariates, higher iron (per one standard deviation, SD increase) was detrimentally associated with - 0.22 mm lower femur length, whereas higher transferrin (per one SD increase) was associated with 0.20 mm higher femur length. Compared with normal subjects (10th-90th percentiles), subjects with extremely high (> 90th percentile) iron concentration were detrimentally associated with lower femur length, birth weight, and chest circumference, and a higher risk of low birth weight, LBW (HR: 3.92, 95%CI: 1.28, 12.0). Subjects with high concentration of soluble transferrin receptor, sTFR and transferrin (> 90th percentile) were associated with higher femur length. Subjects with low concentration of iron and ferritin concentrations (< 10th percentile) were associated with a higher risk of LBW (HR: 4.10, 95%CI: 1.17, 14.3) and macrosomia (HR: 2.79, 95%CI: 1.06, 7.35), respectively. CONCLUSIONS: Maternal iron overload in early pregnancy may be detrimentally associated with neonatal anthropometric indicators and adverse birth outcomes.

CircNOP14 increases the radiosensitivity of hepatocellular carcinoma via inhibition of Ku70-dependent DNA damage repair.

Circular RNAs (circRNAs) are profoundly affected in hepatocellular carcinoma (HCC) through various pathways. However, the role of circRNAs in the radiosensitivity of HCC cells is yet to be explored. In this study, we identified a circRNA-hsa_circ_0006737 (circNOP14) involved in the radiosensitivity of HCC. We found that circNOP14 increased the radiosensitivity of HCC cells both in vitro and in vivo. Notably, using a circRNA pulldown assay and RNA-binding protein immunoprecipitation, we identified Ku70 as a novel and robust interacting protein of circNOP14. Mechanistically, circNOP14 interacts with Ku70 and prevents its nuclear translocation, thereby increasing irradiation-induced DNA damage. Therefore, our findings may provide a predictive indicator and intervention option for 125I brachytherapy or external radiotherapy in HCC.

Mechanism of chromosomal mosaicism in preimplantation embryos and its effect on embryo development.

Aneuploidy is one of the main causes of miscarriage and in vitro fertilization failure. Mitotic abnormalities in preimplantation embryos are the main cause of mosaicism, which may be influenced by several endogenous factors such as relaxation of cell cycle control mechanisms, defects in chromosome cohesion, centrosome aberrations and abnormal spindle assembly, and DNA replication stress. In addition, incomplete trisomy rescue is a rare cause of mosaicism. However, there may be a self-correcting mechanism in mosaic embryos, which allows some mosaicisms to potentially develop into normal embryos. At present, it is difficult to accurately diagnose mosaicism using preimplantation genetic testing for aneuploidy. Therefore, in clinical practice, embryos diagnosed as mosaic should be considered comprehensively based on the specific situation of the patient.

Influence of surface nanostructure-induced innermost ion structuring on capacitance of carbon/ionic liquid double layers.

Ionic liquids have drawn great interest as electrolytes for energy storage applications in which they form characteristic electrical double layers at electrode interfaces. For ionic liquids at carbon electrode interfaces, their double layers are subject to nanoscale structuring of the electrode surface, involving altered ion structure and interactions that significantly influence the double layer capacitance. In this regard, we investigate the modulation of ionic liquid double layers by electrode surface roughness and the resulting effects on the ion structure, interaction, and capacitance. We performed fixed voltage molecular dynamics simulations to compute the differential capacitance profiles for the ionic liquids [BMIm+][TFSI-] and [BMIm+][FSI-] at model carbon electrode interfaces with the surface channel width at subnanometer and nanometer scales. We find that both [BMIm+][TFSI-] and [BMIm+][FSI-] exhibit enhanced differential capacitance for the electrode surface with a subnanometer channel width relative to the flat graphene surface, but the most pronounced enhancements for these two ionic liquids unexpectedly appear at different applied potential regimes. For [BMIm+][TFSI-], the nanostructured electrode shows significant enhancement of capacitance at high positive potential. For [BMIm+][FSI-], on the other hand, this enhancement is small at positive polarization but noticeable at low negative potential. We demonstrate that differences in these capacitance trends is due to differences in ion correlation that arise from a steric constraint of nanostructured electrode surface on the voltage-mediated restructuring of ions closest to the electrode interface. For example, the TFSI- and FSI- anions tend to structure with their charged and nonpolar groups in contact with the positive electrode surface when the constraint on these close-contact anions is relaxed. This anion structuring largely retains the cation association near the nanostructured electrode, resulting in only a slight increase in capacitance at positive polarization. Our simulations highlight the sensitive dependence of the innermost ion structure on the electrode surface nanostructure and applied voltage and the resulting influence on ion correlation and capacitance of ionic liquid double layers.

Reproductive Effect by Rheumatoid Arthritis and Related Autoantibodies.

Rheumatoid arthritis (RA) is a common inflammatory arthritis in women. The effects of RA on the reproductive system are usually overlooked, as RA is not diagnosed until later in reproductive age. Whether RA itself or its related rheumatoid antibodies have an impact on female reproductive function has long been a thought-provoking issue. In brief, relevant epidemiological evidence has shown that women affected by RA are more likely to have coexisting reproductive disorders, including infertility, endometriosis, and premature ovarian insufficiency (POI), or to subsequently develop them. Furthermore, linkage between RA and pregnancy loss (PL) as well as polycystic ovary syndrome (PCOS) is also well known, albeit controversial in available evidence. RA and reproductive disorders appear to share a similar inflammatory immune response and genetic background. The stress experienced by patients with RA may affect their reproductive choices to some extent. Notably, few studies have explored the impact of rheumatoid antibodies such as rheumatoid factors (RFs) and anti-citrullinated protein antibodies (ACPAs) on reproductive disorders. Although it has been mentioned that the rate of RF and/or ACPA positivity is higher in women with a history of PL and POI, the clinical relevance of this relationship and underlying mechanisms still need to be further clarified.

Blood pressure variability supersedes heart rate variability as a real-world measure of dementia risk.

Blood pressure variability (BPV) and heart rate variability (HRV) have been associated with Alzheimer's Disease and Related Dementias (ADRD) in rigorously controlled studies. However, the extent to which BPV and HRV may offer predictive information in real-world, routine clinical care is unclear. In a retrospective cohort study of 48,204 adults (age 54.9 ± 17.5 years, 60% female) receiving continuous care at a single center, we derived BPV and HRV from routinely collected clinical data. We use multivariable Cox models to evaluate the association of BPV and HRV, separately and in combination, with incident ADRD. Over a median 3 [2.4, 3.0] years, there were 443 cases of new-onset ADRD. We found that clinically derived measures of BPV, but not HRV, were consistently associated with incident ADRD. In combined analyses, only patients in both the highest quartile of BPV and lowest quartile of HRV had increased ADRD risk (HR 2.34, 95% CI 1.44-3.81). These results indicate that clinically derived BPV, rather than HRV, offers a consistent and readily available metric for ADRD risk assessment in a real-world patient care setting. Thus, implementation of BPV as a widely accessible tool could allow clinical providers to efficiently identify patients most likely to benefit from comprehensive ADRD screening.