Dual-site OER mechanism exploration through regulating asymmetric multi-site NiOOH.

Asymmetric nickel oxyhydroxide (NiOOH) possesses multi-OH and O active sites on different surfaces, (001) and (001̄), which possibly causes a complicated catalytic process. Density functional theory (DFT) calculations reveal that the unconventional dual-site mechanism (UDSM) of the oxygen evolution reaction (OER) on NiOOH (001) and (001̄) exhibits significantly lower overpotentials of 0.80 and 0.77 V, compared to 1.24 and 1.62 V for the single-site mechanism (SSM), respectively. Through chemical doping or heterojunction modifications, the constructed NiOOH@FeOOH (001̄) heterojunction reduces the thermodynamic overpotential to 0.49 V from original 0.77 V undergoing the UDSM. Although Fe/Co-doping or physical compression yield similar or slightly higher overpotentials and are not conductive to facilitating the OER process by the UDSM, all dual-site paths exhibit obviously lower overpotentials than the SSM for pristine and regulated NiOOH (001) and (001̄) from the whole viewpoint. This work identifies a more reasonable and efficient dual-site OER mechanism, which is expected to help the rational design of highly-efficient electrocatalysts.

Concomitant use of antidepressants and benzodiazepines during pregnancy and associated risk of congenital malformations: a population-based cohort study in Taiwan.

BACKGROUND: Despite the frequent co-administration of antidepressants and benzodiazepines, the association between such concomitant use during pregnancy and the risk of congenital malformations remains inadequately explored. This study aims to examine the association between concomitant use of antidepressants and benzodiazepines during the first trimester and organ-specific congenital malformations. METHODS: We conducted a population-based cohort study using Taiwan's National Birth Certificate Application database, the Maternal and Child Health database, and Taiwan's National Health Insurance database. Pregnant people aged 15-50 years with singleton births between Jan 1, 2004, and Dec 31, 2018, were included. Use of antidepressants and benzodiazepines was defined as at least one prescription during the first trimester, and concomitant use was defined as the overlapping prescription of both drugs with an overlapping prescription period. The primary outcomes were overall congenital malformations and eight organ-specific malformations, consisting of the nervous system, heart, respiratory system, oral cleft, digestive system, urinary system, genital system, and limb malformations. Logistic regression models with propensity score fine stratification weighting approach were used to control for measured confounders. Analyses controlling for confounding by indication and sibling comparison analyses were done to address unmeasured confounders. No individuals with lived experience participated in the research or writing process. FINDINGS: The cohort included 2 634 021 singleton pregnancies, and 8599 (0·3%) individuals were concomitant users of antidepressants and benzodiazepines during the first trimester (mean age at delivery was 31·8 years [SD 5·2] for pregnancies with exposure to antidepressants and benzodiazepines vs 30·7 years [SD 4·9] for pregnancies without exposure). All study participants were female, and information about ethnicity was not available. Absolute risk of overall malformations was 3·81 per 100 pregnancies with exposure, compared with 2·87 per 100 pregnancies without exposure. The propensity score-weighted odds ratios (weighted ORs) did not suggest an increased risk for overall malformations (weighted OR 1·10, 95% CI 0·94-1·28), heart defects (1·01, 0·83-1·23), or any of the other organ-specific malformations, except for digestive system malformations, for which the weighted OR remained statistically significant after adjustment (1·63, 1·06-2·51). The absence of an increased risk for overall congenital malformations associated with concomitant use of antidepressants and benzodiazepines was supported by the analyses controlling for confounding by indication and sibling-matched comparisons. INTERPRETATION: The findings of this study suggest that the concomitant use of antidepressants and benzodiazepines during the first trimester is not associated with a substantial increase in risk for most malformation subtypes. However, considering other potential adverse effects of using both medications concomitantly, a thorough assessment of the risks and benefits is crucial for clinical decision making. FUNDING: National Science and Technology Council.

Activin A as a potential biomarker for preserved ratio impaired spirometry (PRISm) and clinical outcomes in community-dwelling adults.

INTRODUCTION: This study endeavors to decipher the association between Activin A and PRISm, thereby addressing the potential of Activin A as a serum biomarker for early detection and long-term clinical outcome prediction of PRISm and subsequent all-cause mortality. METHODS: The study sample comprised middle-aged and older adults from the I-Lan Longitudinal Aging Study. Pulmonary function including forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were measured. Demographic data and laboratory data (including serum Activin A levels) were also collected. Multivariate logistic regression and Cox proportional hazards models were used to identify independent predictors of PRISm and all-cause mortality, respectively. RESULTS: Among 711 eligible participants, 34 % had PRISm. The risk of PRISm elevated with Activin A levels in group quartiles (adjusted odds ratio (aOR), Q2: 1.606 [95 % CI 0.972-2.652], p = 0.064, Q3: 2.666 [1.635-4.348], p < 0.001, Q4: 3.225 [1.965-5.293], p < 0.001). On the other hand, lower hemoglobin (aOR: 1.122, p = 0.041) and higher blood urea nitrogen (BUN) levels (aOR: 1.033, p = 0.048) were associated with increased risk of PRISm. In addition, the PRISm group had a higher all-cause mortality rate (non-PRISm 4.5% vs. PRISm 8.3 %, p = 0.038). Multivariate Cox models also identify a higher level of Activin A as a risk factor of all-cause mortality (aHR: 1.001 [1.000-1.003], p = 0.042). CONCLUSIONS: Higher Activin A quartiles were linked to increased risk of PRISm, along with lower hemoglobin and higher BUN levels. Additonally, elevated Activin A was a significant risk factor of all-cause mortality.

2D MXene Biomaterials for Catalytic Medical Applications.

In recent years, two-dimensional transition metal carbides, nitrides, and carbonitrides, termed as MXenes, have been widely applied in energy storage, photocatalysis and biomedicine owing to their unique physicochemical properties of large specific surface area, high electrical conductivity, excellent optical performance, good stability, etc. Moreover, due to their strong light absorption capacity in the first and second near-infrared bio-window, and their ability of being simply functionalized with multiple organic/inorganic materials, MXene biomaterials have shown great potential in the field of catalytic therapy. This review will summarize the common catalytic mechanism of MXene biomaterials and their latest applications in catalytic medicine such as tumor therapy, antibacterial and anti-inflammatory, and present the current challenges and opportunities in clinical translation for future development to promote the advancement of MXene biomaterials in the field of catalytic medicine.

The distinct impacts of sarcopenic and dynapenic obesity on mortality in middle-aged and older adults based on different adiposity metrics: Results from I-Lan Longitudinal Aging Study.

BACKGROUND & AIMS: Sarcopenic obesity (SO) and dynapenic obesity (DO) represent two manifestations of excessive fat accumulation concurrent with compromised muscle mass and function, thereby necessitating an examination of their implications for health. This study aims to investigate the relationship between SO/DO and mortality, taking into account various adiposity measures and existing sarcopenia criteria, with further stratified analyses based on age and gender. METHODS: The study sample comprised 1779 older adults residing in the community from the I-Lan Longitudinal Aging Study (ILAS). Body composition was assessed via dual-energy X-ray absorptiometry. The diagnosis of sarcopenia was adhered to the 2019 consensus of the Asian Working Group for Sarcopenia, while adiposity was measured by waist circumference (WC), body mass index (BMI), and fat percentage. SO/DO was defined as the coexistence of sarcopenia/dynapenia and obesity. Multivariate Cox proportional hazard regression models were adopted to examine the association between SO or DO, defined by WC, BMI, fat percentage, and mortality. RESULTS: This 11-year follow-up study of 1779 participants aged 63.9 ± 9.2 years involved 15,068 person-years and 229 deaths. WC-defined SO (HR 1.9, 95% CI 1.1-3.3, p = 0.021) and WC-defined DO (HR 1.4, 95% CI 1.1-1.9, p = 0.022) significantly increased mortality risk, whereas definitions employing alternative adiposity metrics exhibited no statistical significance. WC-defined SO was associated with increased risk of mortality among middle-aged adults, while WC-defined DO was associated with increased risk of mortality among older adults. In sex-specific analysis, WC-defined DO was also associated with increased risk of mortality in men (HR 1.6, 95% CI 1.1-2.4, p = 0.019), while defined by other measurements showed no associations in both sexes. CONCLUSIONS: The study identified a significant link between SO/DO, defined by WC, and an 11-year mortality risk, advocating for WC-defined adiposity as an obesity measure and personalized interventions considering SO and DO's distinct impacts on mortality in middle-aged and older adults.

Dissecting the vascular-cognitive nexus: energetic vs. conventional hemodynamic parameters.

Blood pressure or flow measurements have been associated with vascular health and cognitive function. We proposed that energetic hemodynamic parameters may provide a more nuanced understanding and stronger correlation with cognitive function, in comparisons with conventional aortic and carotid pressure and flow parameters. The study comprised 1858 participants, in whom we assessed cognitive function via MoCA method, and measured central aortic and carotid pressure and flow waveforms. In addition to various pressure and flow parameters, we calculated energetic hemodynamic parameters through integration of pressure multiplying flow with respect to time. Energetic hemodynamic parameters, particularly aortic and carotid mean and pulsatile energy and pulsatility index (PI), were significantly associated with MoCA score more than any aortic and carotid pressure and flow parameters, after adjusting for age, sex, education, depression score, heart rate, BMI, HDL-cholesterol, and glucose levels. MoCA exhibited a strong positive relationship with carotid mean energy (standardized beta = 0.053, P = 0.0253) and a negative relationship with carotid energy PI (standardized beta = -0.093, P = 0.0002), exceeding the association with all traditional pressure- or flow-based parameters. Aortic pressure reflection coefficient at the aorto-carotid junction was positively correlated with mean carotid energy and negatively correlated with PI. Aortic characteristic impedance positively correlated with carotid energy PI but not mean energy. Our research indicates that energetic hemodynamic parameters, particularly carotid mean energy and carotid energy PI, have a stronger association with MoCA scores than traditional pressure- or flow-based metrics. This correlation with cognitive function is notably influenced by the properties of the aorto-carotid interface.

Research on the mechanism of sea buckthorn leaf Fu tea in the treatment of hyperlipidemia.

Background: Hyperlipidemia (HLP) presents a significant challenge to global public health. Mounting evidence suggests that statins, the recommended first-line lipid-lowering agents, have significant adverse effects. Consequently, the quest for natural and efficacious alternative therapies is steadily emerging as a research priority for HLP prevention and treatment. Consumption of tea, which is rich in diverse biologically active compounds with the capacity to regulate lipid metabolism and combat obesity, has emerged as a promising alternative therapy. Sea buckthorn leaves are rich in a multitude of biologically active substances, have a hypolipidemic effect, and can be used as a raw material for tea because of their unique flavor. There is a suggestion that combining Aspergillus cristatus with tea could modify or boost the lipid-lowering active compounds present in tea, thereby increasing its efficacy in regulating lipid metabolism. Results: Sea Buckthorn Leaf Fu Tea (SBLFT) was obtained by fermentation when sea buckthorn leaves contained 42 % moisture, inoculated with Aspergillus cristatus 0.2 mL/g, and incubated for 8 d at constant temperature. Animal experiments demonstrated that SBLFT significantly inhibited body weight gain in HLP rats and reduced lipid content and serum oxidative stress. In addition, liver tissue sections and functional indices showed that SBLFT can improve liver morphology and function abnormalities. Reverse transcription-polymerase chain reaction results indicated that the expression of Liver kinase B1 (LKB1), adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK), acetyl CoA carboxylase 1 (ACC1), and sterol-regulatory element binding protein-1 (SREBP1c) gene related to lipid metabolism was altered. Conclusion: SBLFT improved HLP, specifically via promoting the expression of LKB1 in the liver of HLP rats, activating AMPK, and inhibiting ACC1 and SREBP1c expression, resulting in the inhibition of fatty acid and triglyceride synthesis-related enzymes at the transcriptional level.

Cyclic adenosine 3', 5'-monophosphate (cAMP) signaling is a crucial therapeutic target for ulcerative colitis.

The pathogenesis of ulcerative colitis (UC), a chronic intestine inflammatory disease primarily affecting adolescents, remains uncertain. Contemporary studies suggest that a confluence of elements, including genetic predispositions, environmental catalysts, dysregulated immune responses, and disturbances in the gut microbiome, are instrumental in the initiation and advancement of UC. Among them, inflammatory activation and mucosal barrier damage caused by abnormal immune regulation are essential links in the development of UC. The impairment of the mucosal barrier is intricately linked to the interplay of various cellular mechanisms, including oxidative stress, autophagy, and programmed cell death. An extensive corpus of research has elucidated that level of cyclic adenosine 3',5'-monophosphate (cAMP) undergo modifications in the midst of inflammation and participate in a diverse array of cellular operations that mitigate inflammation and the impairment of the mucosal barrier. Consequently, a plethora of pharmacological agents are currently under development, with some advancing through clinical trials, and are anticipated to garner approval as novel therapeutics. In summary, cAMP exerts a crucial influence on the onset and progression of UC, with fluctuations in its activity being intimately associated with the severity of the disease's manifestation. Significantly, this review unveils the paramount role of cAMP in the advancement of UC, offering a tactical approach for the clinical management of individuals afflicted with UC.

Loss of cell junctional components and matrix alterations drive cell desquamation and fibrotic changes in Idiopathic Pulmonary Fibrosis.

The distal bronchioles in Idiopathic Pulmonary Fibrosis (IPF) exhibit histopathological abnormalities such as bronchiolization, peribronchiolar fibrosis and honeycomb cysts that contribute to the overall architectural remodeling of lung tissue seen in the disease. Here we describe an additional histopathologic finding of epithelial desquamation in patients with IPF, wherein epithelial cells detach from the basement membrane of the distal bronchioles. To understand the mechanism driving this pathology, we performed spatial transcriptomics of the epithelial cells and spatial proteomics of the basement membrane of the distal bronchioles from IPF patients and patients with no prior history of lung disease. Our findings reveal a downregulation of cell junctional components, upregulation of epithelial-mesenchymal transition signatures and dysregulated basement membrane matrix in IPF distal bronchioles, facilitating epithelial desquamation. Further, functional assays identified regulation between Collagen IV in the matrix, and the junctional genes JUP and PLEC , that is crucial for maintaining distal bronchiolar homeostasis. In IPF, this balanced regulation between matrix and cell-junctions is disrupted, leading to loss of epithelial adhesion, peribronchiolar fibrosis and epithelial desquamation. Overall, our study suggests that in IPF the interplay between the loss of cell junctions and a dysregulated matrix results in desquamation of distal bronchiolar epithelium and lung remodeling, exacerbating the disease. One Sentence Summary: Two-way regulation of cell junctional proteins and matrix proteins drives cellular desquamation and fibrosis in the distal bronchioles of patients with Idiopathic Pulmonary Fibrosis.

Establishment of an acute arterial mesenteric ischaemia model in canines with an endovascular approach.

Purpose: This study aimed to evaluate the feasibility of establishing an arterial acute mesenteric ischemia (AMI) model in canines using transcatheter autologous thrombus administration. Materials and methods: Ten canines were divided into the experimental group (Group A, n = 5) and the sham group (Group B, n = 5). The canines in Group A received thrombus administration to the superior mesenteric artery (SMA) through a guiding catheter, while the canines in Group B received normal saline administration. Blood samples were collected and tested at baseline and 2 h after modelling. Canines in Group A underwent manual thromboaspiration after blood and intestine samples were collected. Ischaemic grades of intestinal mucosa were evaluated under light microscopes. Results: The AMI models were successfully conducted in all canines without procedure-related vessel injury or death. At the 2-h follow-up, the high-sensitivity C-reactive protein and D-dimer in Group A were significantly higher than in Group B (5.72 ± 1.8 mg/L vs. 2.82 ± 1.5 mg/L, p = 0.024; 2.25 ± 0.8 µg/mL vs. 0.27 ± 0.10 µg/mL, p = 0.005; respectively). The mean histopathologic intestinal ischaemic grade in Group A was significantly higher than in Group B (2.4 ± 0.5 vs. 0.8 ± 0.4, p < 0.001). After a median of 2 times of thromboaspiration, 80% (4/5) of the canines achieved complete SMA revascularisation. Conclusion: This experimental study demonstrated that establishing an arterial model in canines using endovascular approaches was feasible. The present model may play an important role in the investigation of endovascular techniques in the treatment of arterial AMI.

Comparison of low and standard pneumoperitoneum pressure in laparoscopic pediatric inguinal hernia repair.

Introduction: The effectiveness and safety of low pneumoperitoneum in laparoscopic pediatric inguinal hernia repair is unclear and required to explore. Aim: To evaluate the benefits of low (LPP) vs. standard pneumoperitoneum pressure (SPP) in laparoscopic pediatric inguinal hernia repair. Material and methods: We performed a retrospective cohort analysis of patients with pediatric inguinal hernia. The patients were divided into LPP and SPP groups. Anesthesia and postoperative characteristics were analyzed. Results: We enrolled 169 eligible patients in this study. Anesthesia and postanesthesia care unit times in the LPP group were lower than those in the SPP group (p = 0.00, p = 0.01, respectively). The LPP group had lower values for peak partial pressure of end-tidal carbon dioxide (PETCO2; mm Hg) (33.37 ±4.09 vs. 36.56 ±4.08), trough PETCO2 (38.33 ±5.04 vs. 40.46 ±4.14), and PETCO2 at the end of surgery (35.29 ±4.59 vs. 38.76 ±4.22). The LPP group required less sufentanil citrate (8.76 ±4.07 ml vs. 18.03 ±16.04 ml) and midazolam (1.56 ±0.45 ml vs 1.79 ±0.59 ml) vs. the SPP group, respectively. There was no significant difference between the groups regarding postoperative complications. Conclusions: LPP was associated with shorter anesthesia and postanesthesia care unit times, and lower PETCO2 values compared with SPP. Compared with the SPP group, the LPP group had comparable operation times and postoperative complications. However, long-term outcome studies are needed.

A randomized, double-blind, placebo-controlled study of Cistanche tubulosa and Ginkgo biloba extracts for the improvement of cognitive function in middle-aged and elderly people.

Mild cognitive impairment poses an increasing challenge to middle-aged and elderly populations. Traditional Chinese medicinal herbs like Cistanche tubulosa and Ginkgo biloba (CG) have been proposed as potential agents to improve cognitive and memory functions. A randomized controlled trial involving 100 Chinese middle-aged and elderly participants was conducted to investigate the potential synergistic effects of CG on cognitive function in individuals at risk of neurodegenerative diseases. Over 90 days, both CG group and placebo group received two tablets daily, with each pair of CG tablets containing 72 mg echinacoside and 27 mg flavonol glycosides. Cognitive functions were assessed using multiple scales and blood biomarkers were determined at baseline, Day 45, and Day 90. The CG group exhibited significant improvements in the scores of Mini-Mental State Examination (26.5 at baseline vs. 27.1 at Day 90, p < 0.001), Montreal Cognitive Assessment (23.4 at baseline vs. 25.3 at Day 90, p < 0.001), and World Health Organization Quality of Life (81.6 at baseline vs. 84.2 at Day 90, p < 0.001), all surpassing scores in placebo group. Notably, both the Cognitrax matrix test and the Wechsler Memory Scale-Revised demonstrated enhanced memory functions, including long-term and delayed memory, after CG intervention. Moreover, cognitive-related blood biomarkers, including total tau, pT181, pS199, pT231, pS396, and thyroid-stimulating hormone, significantly decreased, whereas triiodothyronine and free triiodothyronine significantly increased. No treatment-related adverse events were reported, and routine blood and urine tests remained stable. These findings indicated that CG supplementation could potentially serve as an effective supplementary solution for enhancing cognitive and memory functions.

Unexpected Self-Assembly of Nanographene Oxide Membranes upon Electron Beam Irradiation for Ultrafast Ion Sieving.

Nanographene oxide (nGO) flakes-graphene oxide with a lateral size of ≈100 nm or less-hold great promise for superior flux and energy-efficient nanofiltration membranes for desalination and precise ionic sieving owing to their unique high-density water channels with less tortuousness. However, their potential usage is currently limited by several challenges, including the tricky self-assembly of nano-sized flakes on substrates with micron-sized pores, severe swelling in aqueous solutions, and mechanical instability. Herein, the successful fabrication of a robust membrane stacked with nGO flakes on a substrate with a pore size of 0.22 µm by vacuum filtration is reported. This membrane achieved an unprecedented water permeance above 819.1 LMH bar-1, with a high rejection rate of 99.7% for multivalent metal ions. The nGO flakes prepared using an electron beam irradiation method, have uniquely pure hydroxyl groups and abundant aromatic regions. The calculations revealed the strong hydrogen bonds between two nGO flakes, which arise from hydroxyl groups, coupled with hydrophobic aromatic regions, greatly enhance the stability of stacked flakes in aqueous solutions and increase their effective lateral size. The research presents a simple yet effective approach toward the fabrication of advanced 2D nanographene membranes with superior performance for ion sieving applications.

Left Bundle Branch Area Pacing With or Without Conduction System Capture in Heart Failure Models.

BACKGROUND: Left bundle branch area pacing includes left bundle branch pacing (LBBP) and left ventricular septal pacing (LVSP), which is effective in patients with dyssynchronous heart failure (DHF). However, the basic mechanisms are unknown. OBJECTIVES: This study aimed to compare LBBP with LVSP and explore potential mechanisms underlying the better clinical outcomes of LBBP. METHODS: A total of 24 beagles were assigned to the following groups: 1) control group; 2) DHF group, left bundle branch ablation followed by 6 weeks of AOO pacing at 200 ppm; 3) LBBP group, DHF for 3 weeks followed by 3 weeks of DOO pacing at 200 ppm; and 4) LVSP with the same interventions in the LBBP group. Metrics of electrocardiogram, echocardiography, hemodynamics, and expression of left ventricular proteins were evaluated. RESULTS: Compared with LVSP, LBBP had better peak strain dispersion (44.67 ± 1.75 ms vs 55.50 ± 4.85 ms; P < 0.001) and hemodynamic effect (dP/dtmax improvement: 27.16% ± 7.79% vs 11.37% ± 4.73%; P < 0.001), whereas no significant differences in cardiac function were shown. The altered expressions of proteins in the lateral wall vs septum in the DHF group were partially reversed by LBBP and LVSP, which was associated with the contraction and adhesion process, separately. CONCLUSIONS: The animal study demonstrated that LBBP offered better mechanical synchrony and improved hemodynamics than LVSP, which might be explained by the reversed expression of contraction proteins. These results supported the potential superiority of left bundle branch area pacing with the capture of the conduction system in DHF model.

Vertical distribution of microplastics in sediment columns along the coastline of China.

At present, there has been relatively less coverage of microplastics (MPs) pollution in sediment columns, especially across a large geographical span. This study collected sediment columns across 11 provinces along the coastline of China for MPs pollution investigation. The study found higher MPs diversity (Simpson diversity index) in sediment columns than in surface sediments, mostly comprising fiber MPs with dominant transparent and blue colors. Lower MPs pollution was noted in mangrove reserves, while estuarine and coastal areas showed higher pollution levels. Spearman correlation analysis shows that vertical of MPs abundance significantly decreased with depth at 6 of 11 sites. Large-sized MPs with diverse colors in deeper sediments (>40 cm) suggests that burial processes may render MPs more resistant to degradation. Our research highlights varied MPs distribution in coastal sediment, aiding future marine MPs pollution prediction and assessment.

Machine Learning in Hypertrophic Cardiomyopathy: Nonlinear Model From Clinical and CMR Features Predicting Cardiovascular Events.

BACKGROUND: The cumulative burden of hypertrophic cardiomyopathy (HCM) is significant, with a noteworthy percentage (10%-15%) of patients with HCM per year experiencing major adverse cardiovascular events (MACEs). A current risk stratification scheme for HCM had only limited accuracy in predicting sudden cardiac death (SCD) and failed to account for a broader spectrum of adverse cardiovascular events and cardiac magnetic resonance (CMR) parameters. OBJECTIVES: This study sought to develop and evaluate a machine learning (ML) framework that integrates CMR imaging and clinical characteristics to predict MACEs in patients with HCM. METHODS: A total of 758 patients with HCM (67% male; aged 49 ± 14 years) who were admitted between 2010 and 2017 from 4 medical centers were included. The ML model was built on the internal discovery cohort (533 patients with HCM, admitted to Fuwai Hospital, Beijing, China) by using the light gradient-boosting machine and internally evaluated using cross-validation. The external test cohort consisted of 225 patients with HCM from 3 medical centers. A total of 14 CMR imaging features (strain and late gadolinium enhancement [LGE]) and 23 clinical variables were evaluated and used to inform the ML model. MACEs included a composite of arrhythmic events, SCD, heart failure, and atrial fibrillation-related stroke. RESULTS: MACEs occurred in 191 (25%) patients over a median follow-up period of 109.0 months (Q1-Q3: 73.0-118.8 months). Our ML model achieved areas under the curve (AUCs) of 0.830 and 0.812 (internally and externally, respectively). The model outperformed the classic HCM Risk-SCD model, with significant improvement (P < 0.001) of 22.7% in the AUC. Using the cubic spline analysis, the study showed that the extent of LGE and the impairment of global radial strain (GRS) and global circumferential strain (GCS) were nonlinearly correlated with MACEs: an elevated risk of adverse cardiovascular events was observed when these parameters reached the high enough second tertiles (11.6% for LGE, 25.8% for GRS, -17.3% for GCS). CONCLUSIONS: ML-empowered risk stratification using CMR and clinical features enabled accurate MACE prediction beyond the classic HCM Risk-SCD model. In addition, the nonlinear correlation between CMR features (LGE and left ventricular pressure gradient) and MACEs uncovered in this study provides valuable insights for the clinical assessment and management of HCM.

Kneadable dough-type hydrogel transforming from dynamic to rigid network to repair irregular bone defects.

Irregular bone defects, characterized by unpredictable size, shape, and depth, pose a major challenge to clinical treatment. Although various bone grafts are available, none can fully meet the repair needs of the defective area. Here, this study fabricates a dough-type hydrogel (DR-Net), in which the first dynamic network is generated by coordination between thiol groups and silver ions, thereby possessing kneadability to adapt to various irregular bone defects. The second rigid covalent network is formed through photocrosslinking, maintaining the osteogenic space under external forces and achieving a better match with the bone regeneration process. In vitro, an irregular alveolar bone defect is established in the fresh porcine mandible, and the dough-type hydrogel exhibits outstanding shape adaptability, perfectly matching the morphology of the bone defect. After photocuring, the storage modulus of the hydrogel increases 8.6 times, from 3.7 kPa (before irradiation) to 32 kPa (after irradiation). Furthermore, this hydrogel enables effective loading of P24 peptide, which potently accelerates bone repair in Sprague-Dawley (SD) rats with critical calvarial defects. Overall, the dough-type hydrogel with kneadability, space-maintaining capability, and osteogenic activity exhibits exceptional potential for clinical translation in treating irregular bone defects.

Effects of different energy levels in low-protein diet on liver lipid metabolism in the late-phase laying hens through the gut-liver axis.

BACKGROUND: The energy/protein imbalance in a low-protein diet induces lipid metabolism disorders in late-phase laying hens. Reducing energy levels in the low-protein diet to adjust the energy-to-protein ratio may improve fat deposition, but this also decreases the laying performance of hens. This study investigated the mechanism by which different energy levels in the low-protein diet influences liver lipid metabolism in late-phase laying hens through the enterohepatic axis to guide feed optimization and nutrition strategies. A total of 288 laying hens were randomly allocated to the normal-energy and normal-protein diet group (positive control: CK) or 1 of 3 groups: low-energy and low-protein diet (LL), normal-energy and low-protein diet (NL), and high-energy and low-protein diet (HL) groups. The energy-to-protein ratios of the CK, LL, NL, and HL diets were 0.67, 0.74, 0.77, and 0.80, respectively. RESULTS: Compared with the CK group, egg quality deteriorated with increasing energy intake in late-phase laying hens fed low-protein diet. Hens fed LL, NL, and HL diets had significantly higher triglyceride, total cholesterol, acetyl-CoA carboxylase, and fatty acid synthase levels, but significantly lower hepatic lipase levels compared with the CK group. Liver transcriptome sequencing revealed that genes involved in fatty acid beta-oxidation (ACOX1, HADHA, EHHADH, and ACAA1) were downregulated, whereas genes related to fatty acid synthesis (SCD, FASN, and ACACA) were upregulated in LL group compared with the CK group. Comparison of the cecal microbiome showed that in hens fed an LL diet, Lactobacillus and Desulfovibrio were enriched, whereas riboflavin metabolism was suppressed. Cecal metabolites that were most significantly affected by the LL diet included several vitamins, such as riboflavin (vitamin B2), pantethine (vitamin B5 derivative), pyridoxine (vitamin B6), and 4-pyridoxic acid. CONCLUSION: A lipid metabolism disorder due to deficiencies of vitamin B2 and pantethine originating from the metabolism of the cecal microbiome may be the underlying reason for fat accumulation in the liver of late-phase laying hens fed an LL diet. Based on the present study, we propose that targeting vitamin B2 and pantethine (vitamin B5 derivative) might be an effective strategy for improving lipid metabolism in late-phase laying hens fed a low-protein diet.

Determination of trace heavy metal elements in litterfall by inductively coupled plasma optical emission spectrometry after extraction using choline chloride-based deep eutectic solvents.

The development of a green, safe, and accurate sample preparation method for the determination of trace metal elements in environmental samples is of great importance. Choline chloride-based deep eutectic solvents (DESs) were used to extract heavy metal elements from litterfall and the target analytes were measured using inductively coupled plasma optical emission spectrometry. Factors such as the type, ratio, dosage, and extraction time and temperature of the DESs were studied. A DES system based on choline chloride and maleic acid had the highest extraction efficiency of 98.5%, 88.4%, 90.2%, and 93.7% for Cd, Cu, Zn, and Fe. Under the optimized conditions, the limits of detection and limits of quantification were in the range of 0.04-0.70 and 0.13-2.30 mg kg-1. The repeatability (n = 3), estimated in terms of the relative standard deviation, ranged from 1.14% to 3.40%. The proposed method was validated for accuracy using GBW10087. Notably, the energy consumption of the newly developed method was only one-fifth that of a traditional acid digestion method. This work not only presents an environmentally friendly method for the determination of trace element concentrations in environmental samples but also deepens our understanding of DES systems.