Combined Effect of Hydrophilic Pore and the Type of Protons on Proton Conductivity in Porous Metal-Organic Frameworks: A Feasible Approach to Achieve a Super Proton Conductor under Hydrated Conditions.

There has been a steady growth of interest in proton-conductive metal-organic frameworks (MOFs) due to their potential utility in proton-exchange membrane fuel cells. To attain a super proton conductivity (>1 × 10-2 S cm-1) in a MOF-based proton conductor is a key step toward practical application. Currently, most studies are focused on enhancing the proton conductivity of porous MOFs by controlling a single factor, such as the type of protons or hydrophilic pore or hydrogen bond. However, a limited contribution from a single factor cannot afford to remarkably increase the proton conductivity of the MOF and form a super proton conductor. Herein, we constructed two distinct porous MOFs, {(H3O+)4[Cu12(ci)12(OH)4(H2O)12]·3H2O·9DMF} (Cu-ci-3D, H2ci = 1H-indazole-5-carboxylic acid, DMF = N,N'-dimethylformamide) and {[Co(Hppca)2]·2HN(CH3)2·CH3OH·2H2O} (Co-ppca-2D, H2ppca = 5-(pyridin-3-yl)-1H-pyrazole-3-carboxylic acid), to tune their proton conductivities at high relative humidity (RH) using the combined effect of hydrophilic pore and the type of protons, ultimately achieving super proton conduction. Excitingly, Cu-ci-3D indeed harvests a super proton conductivity of 1.37 × 10-2 S cm-1 at 353 K and ∼97% RH, superior to some previously reported MOF-based proton conductors. The results present a unique perspective for developing high-performance MOF-based proton conductors and understanding their structure-performance relationships.

Quantification of 3-Dimensional Confluence-Atrial Morphology in Supracardiac Total Anomalous Pulmonary Venous Connection.

Background: Pulmonary vein stenosis (PVS) continues to be a major complication after surgical repair of total anomalous pulmonary venous connection (TAPVC). Recent studies suggest that the morphology of pulmonary venous confluence and the left atrium (LA) is associated with PVS. However, there are limited data on the prognostic value of integrating quantitative confluence-atrial morphology into risk stratification. Objectives: This study sought to evaluate the prognostic impact of novel imaging metrics derived from 3-dimensional (3D) computed tomography angiography (CTA) modeling on postsurgical PVS (PPVS) in the supracardiac TAPVC (sTAPVC) setting. Methods: Patients undergoing sTAPVC repair in 2017 to 2022 from 3 centers were retrospectively reviewed. Study investigators developed 3D CTA modeled geometric features to quantify confluence-atrial morphology that were analyzed with regard to PPVS. Results: Of the 162 patients (median age 61 days; 55% having preoperative pulmonary venous obstruction [prePVO]) included, 47 (29%) with PPVS at a median of 1.5 months ([quartile 1-quartile 3: 1.5-3.0 months]). In the univariable analysis, the indexed total volume of the LA and confluence (iTVLC) and the ratio of the corresponding confluence length to the mean distance between the LA and confluence (CCL/mDBLC ratio) were significantly associated with PPVS. In a multivariable model adjusting for prePVO and age, the iTVLC and CCL/mDBLC ratio independently predicted PPVS (HR: 1.15; 95% CI: 1.06-1.25; and HR: 1.20; 95% CI: 1.08-1.35, respectively, all P < 0.01). Specifically, an iTVLC ≥20 cm3/m2 and a CCL/mDBLC ratio ≥7.7 were significantly associated with a reduced risk of PPVS. Conclusions: Quantification of 3D confluence-atrial morphology appears to offer a deeper and better metric to predict PPVS in patients with sTAPVC.

Implementation of Accurate Parameter Identification for Proton Exchange Membrane Fuel Cells and Photovoltaic Cells Based on Improved Honey Badger Algorithm.

Predicting the system efficiency of green energy and developing forward-looking power technologies are key points to accelerating the global energy transition. This research focuses on optimizing the parameters of proton exchange membrane fuel cells (PEMFCs) and photovoltaic (PV) cells using the honey badger algorithm (HBA), a swarm intelligence algorithm, to accurately present the performance characteristics and efficiency of the systems. Although the HBA has a fast search speed, it was found that the algorithm's search stability is relatively low. Therefore, this study also enhances the HBA's global search capability through the rapid iterative characteristics of spiral search. This method will effectively expand the algorithm's functional search range in a multidimensional and complex solution space. Additionally, the introduction of a sigmoid function will smoothen the algorithm's exploration and exploitation mechanisms. To test the robustness of the proposed methodology, an extensive test was conducted using the CEC'17 benchmark functions set and real-life applications of PEMFC and PV cells. The results of the aforementioned test proved that with regard to the optimization of PEMFC and PV cell parameters, the improved HBA is significantly advantageous to the original in terms of both solving capability and speed. The results of this research study not only make definite progress in the field of bio-inspired computing but, more importantly, provide a rapid and accurate method for predicting the maximum power point for fuel cells and photovoltaic cells, offering a more efficient and intelligent solution for green energy.

Investigation of Biomechanical Differences in Level Walking between Patients with Bilateral and Unilateral Total Knee Replacements.

Due to the high risk of a bilateral total knee arthroplasty (TKR) following unilateral TKR, this study was performed to investigate bilateral TKR patients. Specifically, we examined biomechanical differences between the first replaced and second replaced limbs of bilateral patients. Furthermore, we examined bilateral TKR effects on hip, knee, and ankle biomechanics, compared to the replaced and non-replaced limbs of unilateral patients. Eleven bilateral patients (70.09 ± 5.41 years, 1.71 ± 0.08 m, 91.78 ± 13.00 kg) and fifteen unilateral TKR patients (65.67 ± 6.18 years, 1.73 ± 0.10 m, 87.72 ± 15.70 kg) were analyzed while performing level walking. A repeated measures one-way ANOVA was performed to analyze between-limb differences within the bilateral TKR group. A 2 × 2 (limb × group) ANOVA was used to determine differences between bilateral and unilateral patients. Our results showed that the second replaced limb exhibited a lower peak initial-stance knee extension moment than the first replaced limb. No other kinematic or kinetic differences were found. Bilateral patients exhibited lower initial-stance knee extension moments, knee abduction moments, and dorsiflexion moments, compared to unilateral patients. Bilateral patients also exhibited lower push-off peak hip flexion moments and vertical GRF. The differences between the first and second replaced limbs of bilateral patients may indicate different adaptation strategies used following a second TKR. The significant group differences indicate that adaptations are different between these groups, and it is not recommended to use patients with unilateral and bilateral TKR together in gait analyses.

The survival and cost-effectiveness analysis of adjunctive Chinese medicine therapy for patients with non-small cell lung cancer: a nationwide cohort study in Taiwan.

Introduction: Cancer, particularly lung cancer, is a significant global healthcare challenge. Non-Small Cell Lung Cancer (NSCLC) constitutes 85% of cases. Patients often seek alternative therapies like Chinese medicine alongside Western treatments. This study investigates the survival outcomes and cost-effectiveness of adjunctive Chinese medicine therapy for NSCLC patients in Taiwan. Methods: We utilized the National Health Insurance Research Database in a retrospective cohort study from 2000 to 2018, focusing on NSCLC patients diagnosed between 2007 and 2013. After propensity score matching 1:5 ratio, then compared patients with and without adjunctive Chinese medicine therapy. Survival outcomes, cost-effectiveness, and sensitivity analyses were conducted. Results: The study involved 43,122 NSCLC patients with 5.76% receiving adjunctive Chinese medicine. There is no significant associated between the risk of death and adjuvant Chinese medicine therapy until 181-365 days of adjuvant treatment could reduce the risk of death (HR = 0.88, 95% CI: 0.80-0.98). Cost-effectiveness analysis showed an incremental cost-effectiveness ratio of 880,908 NT$/year. Conclusion: Adjunctive Chinese medicine therapy, particularly when administered for 181-365 days, significantly reduced the mortality risk among stage IV NSCLC patients. The cost-effectiveness aligns with willingness-to-pay thresholds, indicating economic benefit.

Fabrication electro-spun Poly(vinyl alcohol)-Melamine nonwoven membrane composite separator for high-power lithium-ion batteries.

Current commercial separators used in lithium-ion batteries have inherent flaws, especially poor thermal stability, which pose substantial safety risks. This study introduces a high-safety composite membrane made from electrospun poly(vinyl alcohol)-melamine (PVAM) and polyvinylidene fluoride (PVDF) polymer solutions via a dip coating method, designed for high-voltage battery systems. The poly(vinyl alcohol) and melamine components enhance battery safety, while the PVDF coating improves lithium-ion conductivity. The dip-coated PVDF/Esp-PVAM composite separators were evaluated for electrolyte uptake, contact angle, thermal stability, porosity, electrochemical stability and ionic conductivity. Notably, our Dip 1 % PVDF@Esp-PVAM composite separator exhibited excellent wettability and a lithium-ion conductivity of approximately 7.75 × 10⁻4 S cm⁻1 at room temperature. These separators outperformed conventional PE separators in half-cells with Ni-rich NCM811 cathodes, showing exceptional cycling stability with 93.4 % capacity retention after 100 cycles at 1C/1C, as compared to 84.8 % for PE separators. Our Dip 1 % PVDF@Esp-PVAM composite separator demonstrates significant potential for enhancing the long-term durability and high-rate performance of lithium-ion batteries, making it a promising option for long-term energy storage applications.

Contribution of greenness, air pollution, and residential food environment to excess gestational weight gain: A cross-sectional study in Wuhan, China.

OBJECTIVES: Our goal was to explore how greenness, air pollution, and residential food environment were linked to excessive gestational weight gain (EGWG), and to estimate their combined effects on this condition. METHOD: This cross-sectional analysis included 51,507 pregnant women from the Wuhan Maternal and Child Health Management Information System between 2016 and 2019. Generalized linear mixed regression models were employed to explore the relationships between greenness, air pollution, residential food environmental exposure, and EGWG; and the combined effects were further estimated by cluster analysis and principal components analysis. RESULT: We only found a significant association between convenience store density within the 250 m buffer zone (OR = 1.03 and 95% CI: 1.01,1.05) and EGWG. In terms of air pollution, sulfur dioxide(SO2), particulate matter with a diameter of 10 µm or less(PM10), and particulate matter with a diameter of 2.5 µm or less(PM2.5) were substantially correlated with a higher prevalence of EGWG and higher GWG, with (OR = 1.16 and 95% CI: 1.12,1.21; OR = 1.12 and 95% CI: 1.08,1.16; OR = 1.17 and 95% CI: 1.14,1.21, respectively) per interquartile range(IQR) increase. Cluster analysis revealed the presence of three clusters representing urban exposures. In contrast to urban environment clusters characterized by favourable conditions, those exhibiting elevated air pollution levels, high-density residential food environment and low levels of greenness were found to have increased odds of EGWG (OR = 1.10, 95% CI: 1.03, 1.19). CONCLUSION: This study emphasizes that exposure to elevated air pollution, high-density residential neighbourhood food environments, and low levels of greenness is a neighbourhood obesogenic environment for pregnant women.

Assessing CO2 sources and sinks in and around Taiwan: Implication for achieving regional carbon neutrality by 2050.

Taiwan has pledged to achieve net-zero carbon emissions by 2050, but the current extent of carbon sinks in Taiwan remains unclear. Therefore, this study aims to first review the existing nature-based carbon sinks on land and in the oceans around Taiwan. Subsequently, we suggest potential strategies to reduce CO2 emissions and propose carbon dioxide removal methods (CDRs). The natural carbon sinks by forests, sediments, and oceans in and around Taiwan are approximately 21.5, 42.1, and 96.8 Mt-CO2 y-1, respectively, which is significantly less than Taiwan's CO2 emissions (280 Mt-CO2 y-1). Taiwan must consider decarbonization strategies like using electric vehicles, renewable energy, and hydrogen energy by formulating enabling policies. Besides more precisely assessing both terrestrial and marine carbon sinks, Taiwan should develop novel CDRs such as bioenergy with carbon capture and storage, afforestation, reforestation, biochar, seaweed cultivation, and ocean alkalinity enhancement, to reach carbon neutrality by 2050.

Nutrient sources, phytoplankton blooms, and hypoxia along the Chinese coast in the East China Sea: Insight from 2014.

Phytoplankton blooms are common along the Chinese coast in the East China Sea, driven by various nutrient sources including river discharge, bottom water regeneration, and Kuroshio subsurface water intrusion. A notable 2014 summer bloom off the Zhejiang coast, exhibiting a Chl a concentration of 20.1 µg L-1, was significantly influenced by Changjiang River discharge, and high nutrient concentrations are often observed in the region's surface water. During blooms, primary production peaks at 1686.3 mg C m-3 d-1, indicating substantial CO2 absorption, with surface water fCO2 declining to 299.5 µatm, closely linked to plankton activities. Hypoxia often coincides with these frequent bloom occurrences, implicating marine-derived organic matter decomposition as a pivotal factor. Elevated particulate organic carbon concentrations further support this assumption, alongside increased nutrient levels, fCO2, and low pH in hypoxic waters. These findings underscore the intricate interplay between phytoplankton, nutrient cycling, and hypoxia formation, essential for effective coastal ecosystem management.

The impact of flooding from the Minjiang River on the succession of harmful algal blooms (HABs) caused by diatoms in China's offshore waters.

This study examines diatom assemblages in the Matsu Archipelago, an area influenced by Minjiang River runoff. It focuses on harmful algal blooms (HABs) that occurred between August 2021 and July 2022. Utilizing 18S rRNA metabarcoding and microscopic analysis, we observed a significant diatom bloom during early summer runoff, peaking at 5 × 105 cells L-1. The research reveals dynamic community changes during the runoff season, with dominant genera including Pseudo-nitzschia, Chaetoceros, and Skeletonema. Skeletonema cell density correlated with NO3 levels, Chaetoceros had a slight PO4 affinity, and Pseudo-nitzschia showed a negative correlation with Skeletonema. Pseudo-nitzschia, which prefers high light and pH conditions, had notably high concentrations in the flood season and in the autumn. In both, it was dominated by potential toxin-producing species - P. multistriata and P. pungens during the flooding, and P. cuspidate in the autumn. These findings highlight the intricate relationship between diatom dynamics and environmental factors, providing essential insights for managing HABs, especially Pseudo-nitzschia species, amidst environmental changes.

Creatine and L-carnitine attenuate muscular laminopathy in the LMNA mutation transgenic zebrafish.

Lamin A/C gene (LMNA) mutations contribute to severe striated muscle laminopathies, affecting cardiac and skeletal muscles, with limited treatment options. In this study, we delve into the investigations of five distinct LMNA mutations, including three novel variants and two pathogenic variants identified in patients with muscular laminopathy. Our approach employs zebrafish models to comprehensively study these variants. Transgenic zebrafish expressing wild-type LMNA and each mutation undergo extensive morphological profiling, swimming behavior assessments, muscle endurance evaluations, heartbeat measurement, and histopathological analysis of skeletal muscles. Additionally, these models serve as platform for focused drug screening. We explore the transcriptomic landscape through qPCR and RNAseq to unveil altered gene expression profiles in muscle tissues. Larvae of LMNA(L35P), LMNA(E358K), and LMNA(R453W) transgenic fish exhibit reduced swim speed compared to LMNA(WT) measured by DanioVision. All LMNA transgenic adult fish exhibit reduced swim speed compared to LMNA(WT) in T-maze. Moreover, all LMNA transgenic adult fish, except LMNA(E358K), display weaker muscle endurance than LMNA(WT) measured by swimming tunnel. Histochemical staining reveals decreased fiber size in all LMNA mutations transgenic fish, excluding LMNA(WT) fish. Interestingly, LMNA(A539V) and LMNA(E358K) exhibited elevated heartbeats. We recognize potential limitations with transgene overexpression and conducted association calculations to explore its effects on zebrafish phenotypes. Our results suggest lamin A/C overexpression may not directly impact mutant phenotypes, such as impaired swim speed, increased heart rates, or decreased muscle fiber diameter. Utilizing LMNA zebrafish models for drug screening, we identify L-carnitine treatment rescuing muscle endurance in LMNA(L35P) and creatine treatment reversing muscle endurance in LMNA(R453W) zebrafish models. Creatine activates AMPK and mTOR pathways, improving muscle endurance and swim speed in LMNA(R453W) fish. Transcriptomic profiling reveals upstream regulators and affected genes contributing to motor dysfunction, cardiac anomalies, and ion flux dysregulation in LMNA mutant transgenic fish. These findings faithfully mimic clinical manifestations of muscular laminopathies, including dysmorphism, early mortality, decreased fiber size, and muscle dysfunction in zebrafish. Furthermore, our drug screening results suggest L-carnitine and creatine treatments as potential rescuers of muscle endurance in LMNA(L35P) and LMNA(R453W) zebrafish models. Our study offers valuable insights into the future development of potential treatments for LMNA-related muscular laminopathy.

Targeted protein degradation systems to enhance Wnt signaling.

Molecules that facilitate targeted protein degradation (TPD) offer great promise as novel therapeutics. The human hepatic lectin asialoglycoprotein receptor (ASGR) is selectively expressed on hepatocytes. We have previously engineered an anti-ASGR1 antibody-mutant RSPO2 (RSPO2RA) fusion protein (called SWEETS) to drive tissue-specific degradation of ZNRF3/RNF43 E3 ubiquitin ligases, which achieved hepatocyte-specific enhanced Wnt signaling, proliferation, and restored liver function in mouse models, and an antibody-RSPO2RA fusion molecule is currently in human clinical trials. In the current study, we identified two new ASGR1- and ASGR1/2-specific antibodies, 8M24 and 8G8. High-resolution crystal structures of ASGR1:8M24 and ASGR2:8G8 complexes revealed that these antibodies bind to distinct epitopes on opposing sides of ASGR, away from the substrate-binding site. Both antibodies enhanced Wnt activity when assembled as SWEETS molecules with RSPO2RA through specific effects sequestering E3 ligases. In addition, 8M24-RSPO2RA and 8G8-RSPO2RA efficiently downregulate ASGR1 through TPD mechanisms. These results demonstrate the possibility of combining different therapeutic effects and degradation mechanisms in a single molecule.

Design principles and therapeutic applications of novel synthetic WNT signaling agonists.

Wingless-related integration site or Wingless and Int-1 or Wingless-Int (WNT) signaling is crucial for embryonic development, and adult tissue homeostasis and regeneration, through its essential roles in cell fate, patterning, and stem cell regulation. The biophysical characteristics of WNT ligands have hindered efforts to interrogate ligand activity in vivo and prevented their development as therapeutics. Recent breakthroughs have enabled the generation of synthetic WNT signaling molecules that possess characteristics of natural ligands and potently activate the pathway, while also providing distinct advantages for therapeutic development and manufacturing. This review provides a detailed discussion of the protein engineering of these molecular platforms for WNT signaling agonism. We discuss the importance of WNT signaling in several organs and share insights from the initial application of these new classes of molecules in vitro and in vivo. These molecules offer a unique opportunity to enhance our understanding of how WNT signaling agonism promotes tissue repair, enabling targeted development of tailored therapeutics.

Optimizing Coarse-Grained Models for Large-Scale Membrane Protein Simulation.

Coarse-grained (CG) models have been developed for studying membrane proteins at physiologically relevant scales. Such methods, including popular CG lipid models, exhibit stability and efficiency at moderate scales, but they can become impractical or even unusable beyond a critical size due to various technical issues. Here, we report that these scale-dependent issues can arise from progressively slower relaxation dynamics and become confounded by unforeseen instabilities observed only at larger scales. To address these issues, we systemically optimized a 4-site solvent-free CG lipid model that is suitable for conducting micron-scale molecular dynamics simulations of membrane proteins under various membrane properties. We applied this lipid model to explore the long-range membrane deformation induced by a large mechanosensitive ion channel, PIEZO. We show that the optimized CG models are powerful in elucidating the structural and dynamic interplay between PIEZO and the membrane. Furthermore, we anticipate that our methodological insights can prove useful for resolving issues stemming from scale-dependent limitations of similar CG methodologies.

Insight into the research history and trends of total anomalous pulmonary venous connection: a bibliometric analysis.

BACKGROUND: Total anomalous pulmonary venous connection (TAPVC) is a rare congenital heart disease characterized by the inability of all pulmonary veins to connect to the left atrium. Our previous bibliometric article summarized the characteristics of only the 100 most cited papers in TAPVC research. The purpose of this study was to use comprehensive bibliometric analysis to examine the development history, current status, and future trends in the field of TAPVC. METHODS: All publications on TAPVC published between 2000 and 2023 were collected from the Web of Science Core Collection. The publication and citation data were quantitatively analyzed by publication year, country, institution, author, and journal. Co-authorship and co-occurrence analyses were performed using VOSviewer, and keyword and reference bursts were identified using CiteSpace. Pearson's test was used to examine the correlations between two continuous variables. RESULTS: As of July 20, 2023, we identified 368 publications with 3320 citations. These publications were published in 132 journals and authored by 1835 researchers from 457 institutions in 47 countries. For the number of publications, the top country, top institution, top author, and top journals were the United States (n = 82), Shanghai Jiao Tong University (n = 13), Huiwen Chen (n = 9), and Annals of Thoracic Surgery and Pediatric Cardiology (n = 29 each), respectively. For the number of citations, the top country, top affiliation, top author, and top journal were the United States (n = 1348), University of Toronto (n = 250), Christopher A. Caldarone (n = 315), and Annals of Thoracic Surgery (n = 746), respectively. The number of national publications significantly correlated with GDP (R = 0.887, P < 0.001), research & development (R&D) expenditure (R = 0.375, P = 0.013), population (R = 0.694, P < 0.001), and journals (R = 0.751, P < 0.001). The number of national citations significantly correlated with GDP (R = 0.881, P < 0.001), R&D expenditure (R = 0.446, P = 0.003), population (R = 0.305, P = 0.037), and journals (R = 0.917, P < 0.001). International collaboration in the field of TAPVC was not well developed. The most commonly cited publication discussed era changes in mortality and reoperation rate in TAPVC patients. The most common keywords were "total anomalous pulmonary venous connection" and "congenital heart disease". The keyword "case report" appeared most recently, with an average occurrence year of 2021.8. The co-occurrence analysis grouped 26 keywords into six themes: surgical repair of TAPVC, postoperative pulmonary vein stenosis, surgical repair of TAPVC patients with heterotaxy, application of echocardiography in diagnosing TAPVC, application of echocardiography in the prenatal diagnosis of TAPVC, and application of the sutureless technique in the surgical repair of TAPVC patients with right atrial isomerism or a single ventricle. Citation burst detection identified 32 references with citation bursts, seven of which had ongoing citation bursts until 2023. CONCLUSIONS: This study conducted a bibliometric analysis to provide a comprehensive overview of TAPVC research. We hope to offer new ideas for promoting development in the field of TAPVC.

Cancer stages and mortality risk of breast cancer between women with and without disabilities: A national population-based cohort study in Taiwan.

BACKGROUND: The second-most common cause of cancer-related death for women worldwide is breast cancer. However, there is little information about breast cancer among women with disabilities in Taiwan. OBJECTIVES: This study investigated differences between women with and without disabilities regarding breast cancer stages and evaluated the probability of developing an advanced stage and the mortality risk of breast cancer. METHODS: This study conducted a nationwide retrospective cohort study using the National Health Insurance Research Database and other nationwide databases. Our participants were newly diagnosed breast cancer patients, including women with and without disabilities, between 2004 and 2010. We matched both of them with propensity score matching methods (1:5), and all were followed up until the end of 2016. RESULTS: This study included 50,683 participants with breast cancer. After matching, women with disabilities who did not receive breast cancer screening had a more significant proportion of advanced-stage breast cancer (19.95 %) than those without disabilities who did not receive breast cancer screening (16.87 %). After adjusting for related variables, women with disabilities were 1.27 times more likely to have advanced-stage breast cancer than those without disabilities. Additionally, after suffering from breast cancer, individuals with disabilities had a 1.23 times greater mortality risk compared to those without disabilities. CONCLUSIONS: Although cancer stages were controlled, women with disabilities still had a higher mortality risk of breast cancer. Hence, policymakers should pay more attention to women with disabilities to treat them at an early stage, which can reduce the mortality risk attributable to advanced stages.