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ß-glucan, a polysaccharide found in various sources, exhibits unique physicochemical properties, yet its high polymerization limits clinical applications because of its solubility. Addressing this limitation, we introduce PPTEE-glycan, a highly purified soluble ß-1,3/1,6-glucan derived from Aureobasidium pullulans. The refined PPTEE-glycan demonstrated robust immune stimulation in vitro, activated dendritic cells, and enhanced co-stimulatory markers, cytokines, and cross-presentation. Formulated as a PPTEE + microemulsion (ME), it elevated immune responses in vivo, promoting antigen-specific antibodies and CD8+ T cell proliferation. Intratumoral administration of PPTEE + ME in tumor-bearing mice induced notable tumor regression, which was linked to the activation of immunosuppressive cells. This study highlights the potential of high-purity Aureobasidium pullulans-derived ß-glucan, particularly PPTEE, as promising immune adjuvants, offering novel avenues for advancing cancer immunotherapy.
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Introduction: Dispatcher-assisted cardiopulmonary resuscitation (DA-CPR) improves bystander CPR rates and survival outcomes. This study aimed to identify barriers to successful DA-CPR in patients with out-of-hospital cardiac arrest (OHCA). Methods: This retrospective observational study used data from a nationwide OHCA database from 2017 to 2021. Adult emergency medical services (EMS)-treated patients with OHCA with a presumed cardiac etiology were enrolled. The main exposure variable was compliance with DA-CPR. The primary outcome was good neurological recovery at hospital discharge. Multivariable logistic regression analysis was conducted to identify the major factors associated with unsuccessful DA-CPR with and without multiple imputations. Causal mediation analysis was conducted using witnessed status as a mediator. Results: In the final analysis, 49,165 patients with OHCA were included. A total of 36,865 (75.0%) patients successfully underwent DA-CPR. A higher proportion of good neurological recovery was observed in the successful DA-CPR group than in the non-successful DA-CPR group (P < 0.001). The following factors were identified as risk factors for unsuccessful DA-CPR: age > 65 years, male sex, OHCA occurring in a non-metropolitan area or private place, unwitnessed status, whether the bystander was a non-family member or non-cohabitant, female sex or had not received CPR training, and primary call dispatchers not receiving any first-aid training. Additional analyses after multiple imputations showed similar results. Mediation effect was significant for most risk factors for unsuccessful DA-CPR. Conclusions: Bystander characteristics (non-family member or non-cohabitant, female, and uneducated status for CPR) and primary call dispatchers not receiving first-aid training were identified as risk factors for unsuccessful DA-CPR.
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Background: Accurate medical advice is paramount in ensuring optimal patient care, and misinformation can lead to misguided decisions with potentially detrimental health outcomes. The emergence of large language models (LLMs) such as OpenAI's GPT-4 has spurred interest in their potential health care applications, particularly in automated medical consultation. Yet, rigorous investigations comparing their performance to human experts remain sparse. Objective: This study aims to compare the medical accuracy of GPT-4 with human experts in providing medical advice using real-world user-generated queries, with a specific focus on cardiology. It also sought to analyze the performance of GPT-4 and human experts in specific question categories, including drug or medication information and preliminary diagnoses. Methods: We collected 251 pairs of cardiology-specific questions from general users and answers from human experts via an internet portal. GPT-4 was tasked with generating responses to the same questions. Three independent cardiologists (SL, JHK, and JJC) evaluated the answers provided by both human experts and GPT-4. Using a computer interface, each evaluator compared the pairs and determined which answer was superior, and they quantitatively measured the clarity and complexity of the questions as well as the accuracy and appropriateness of the responses, applying a 3-tiered grading scale (low, medium, and high). Furthermore, a linguistic analysis was conducted to compare the length and vocabulary diversity of the responses using word count and type-token ratio. Results: GPT-4 and human experts displayed comparable efficacy in medical accuracy ("GPT-4 is better" at 132/251, 52.6% vs "Human expert is better" at 119/251, 47.4%). In accuracy level categorization, humans had more high-accuracy responses than GPT-4 (50/237, 21.1% vs 30/238, 12.6%) but also a greater proportion of low-accuracy responses (11/237, 4.6% vs 1/238, 0.4%; P=.001). GPT-4 responses were generally longer and used a less diverse vocabulary than those of human experts, potentially enhancing their comprehensibility for general users (sentence count: mean 10.9, SD 4.2 vs mean 5.9, SD 3.7; P<.001; type-token ratio: mean 0.69, SD 0.07 vs mean 0.79, SD 0.09; P<.001). Nevertheless, human experts outperformed GPT-4 in specific question categories, notably those related to drug or medication information and preliminary diagnoses. These findings highlight the limitations of GPT-4 in providing advice based on clinical experience. Conclusions: GPT-4 has shown promising potential in automated medical consultation, with comparable medical accuracy to human experts. However, challenges remain particularly in the realm of nuanced clinical judgment. Future improvements in LLMs may require the integration of specific clinical reasoning pathways and regulatory oversight for safe use. Further research is needed to understand the full potential of LLMs across various medical specialties and conditions.
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Inteligência Artificial , Cardiologia , Humanos , Cardiologia/normasRESUMO
OBJECTIVE: This study investigated the differences in injury profiles and safety device effectiveness among children with road traffic injuries (RTIs) involving passenger vehicles and school buses. METHODS: Using data from the Emergency Department-based Injury In-depth Surveillance database, this multicentre cross-sectional study investigated the injury profiles of 14 669 children aged 12 years old and younger who experienced RTIs from 2011-2021. Demographic factors, injury distribution, severity and effect of safety device use between RITs involving passenger vehicles and school buses were compared. RESULTS: RTIs in children most frequently occurred between 12:00 and 18:00 hours (46.9%). School bus-related RTIs peaked during school commute hours, that is, from 06:00 to 12:00 hours, and were associated with a higher prevalence of head (63.1% vs 58.9%, p<0.05) and extremity injuries (upper extremity: 8.0% vs 6.4% and lower extremity: 11.1% vs 7.6 %, p<0.05) compared with those involving passenger vehicles. However, passenger vehicle crashes showed higher proportions of neck and chest injuries, along with injuries requiring hospitalisation and intensive care. Safety devices exhibited preventive effects against head and lower extremity injuries in both vehicle types. While safety devices showed effective in reducing hospital admissions and severe injuries in passenger vehicles, their effectiveness in school buses was not observed. CONCLUSION: This study highlights the different epidemiology and injury profiles of RTIs among children involving passenger vehicles and school buses. Improved safety devices, particularly in school buses, are necessary to ensure the comprehensive protection of child passengers and reduce the risk of severe injuries during road traffic incidents.
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In 2D noble metals like copper, the carrier scattering at grain boundaries has obscured the intrinsic nature of electronic transport. However, it is demonstrated that the intrinsic nature of transport by hole carriers in 2D copper can be revealed by growing thin films without grain boundaries. As even a slight deviation from the twin boundary is perceived as grain boundaries by electrons, it is only through the thorough elimination of grain boundaries that the hidden hole-like attribute of 2D single-crystal copper can be unmasked. Two types of Fermi surfaces, a large hexagonal Fermi surface centered at the zone center and the triangular Fermi surface around the zone corner, tightly matching to the calculated Fermi surface topology, confirmed by angle-resolved photoemission spectroscopy (ARPES) measurements and vivid nonlinear Hall effects of the 2D single-crystal copper account for the presence of hole carriers experimentally. This breakthrough suggests the potential to manipulate the majority carrier polarity in metals by means of grain boundary engineering in a 2D geometry.
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Targeted and stimuli-responsive drug delivery enhances therapeutic efficacy and minimizes undesirable side effects of cancer treatment. Although cellulose nanocrystals (CNCs) are used as drug carriers because of their robustness, spindle shape, biocompatibility, renewability, and nontoxicity, the lack of programmability and functionality of CNCs-based platforms hampers their application. Thus, high adaptability and the capacity to form dynamic 3D nanostructures of DNA may be advantageous, as they can provide functionalities such as target-specific and stimuli-responsive drug release. Using DNA nanotechnology, the functional polymeric form of DNA nanostructures can be replicated using rolling circle amplification (RCA), and the biologically and physiologically stable DNA nanostructures may overcome the challenges of CNCs. In this study, multifunctional polymeric DNAs produced with RCA were strongly complexed with surface-modified CNCs via electrostatic interactions to form polymeric DNA-decorated CNCs (pDCs). Particle size, polydispersity, zeta potential, and biostability of the nanocomplexes were analyzed. As a proof of concept, the dynamic structural functionalities of DNA nanostructures were verified by observing cancer-targeted intracellular delivery and pH-responsive drug release. pDCs showed anticancer properties without side effects in vitro, owing to their aptamer and i-motif functionalities. In conclusion, pDCs exhibited multifunctional anticancer activities, demonstrating their potential as a promising hybrid nanocomplex platform for targeted cancer therapy.
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Celulose , DNA , Portadores de Fármacos , Liberação Controlada de Fármacos , Nanopartículas , Nanoestruturas , Celulose/química , Humanos , Nanopartículas/química , DNA/química , Nanoestruturas/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/administração & dosagem , Polímeros/química , Concentração de Íons de Hidrogênio , Doxorrubicina/química , Doxorrubicina/farmacologia , Doxorrubicina/administração & dosagem , Sobrevivência Celular/efeitos dos fármacosRESUMO
The subchronic toxicity and toxicokinetics of a combination of rabeprazole sodium and sodium bicarbonate were investigated in dogs by daily oral administration for 13 consecutive weeks with a 4-week recovery period. The dose groups consisted of control (vehicles), (5 + 200), (10 + 400), and (20 + 800) mg/kg of rabeprazole sodium + sodium bicarbonate, 20 mg/kg of rabeprazole sodium only, and 800 mg/kg of sodium bicarbonate only. Esophageal ulceration accompanied by inflammation was observed in only one animal in the male (20 + 800) mg/kg rabeprazole sodium + sodium bicarbonate group. However, the severity of the ulceration was moderate, and the site of occurrence was focally extensive; thus, it was assumed to be a treatment-related effect of rabeprazole sodium + sodium bicarbonate. In the toxicokinetics component of this study, systemic exposure to rabeprazole sodium (AUClast and Cmax at Day 91) was greater in males than females, suggesting sex differences. AUClast and Cmax at Day 91 were increased compared to those on Day 1 in a dose-dependent manner. A delayed Tmax and no drug accumulation were observed after repeated dosage. In conclusion, we suggest under the conditions of this study that the no-observed-adverse-effect level (NOAEL) of the combination of rabeprazole sodium + sodium bicarbonate in male and female dogs is (10 + 400) and (20 + 800) mg/kg, respectively.
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Magnetic anisotropy in atomically thin correlated heterostructures is essential for exploring quantum magnetic phases for next-generation spintronics. Whereas previous studies have mostly focused on van der Waals systems, here we investigate the impact of dimensionality of epitaxially grown correlated oxides down to the monolayer limit on structural, magnetic, and orbital anisotropies. By designing oxide superlattices with a correlated ferromagnetic SrRuO3 and nonmagnetic SrTiO3 layers, we observed modulated ferromagnetic behavior with the change of the SrRuO3 thickness. Especially, for three-unit-cell-thick layers, we observe a significant 1500% improvement of the coercive field in the anomalous Hall effect, which cannot be solely attributed to the dimensional crossover in ferromagnetism. The atomic-scale heterostructures further reveal the systematic modulation of anisotropy for the lattice structure and orbital hybridization, explaining the enhanced magnetic anisotropy. Our findings provide valuable insights into engineering the anisotropic hybridization of synthetic magnetic crystals, offering a tunable spin order for various applications.
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Homochirality is an important feature in biological systems and occurs even in inorganic nanoparticles. However, the mechanism of chirality formation and the key steps during growth are not fully understood. Here we identify two distinguishable pathways from achiral to chiral morphologies in gold nanoparticles by training an artificial neural network of cellular automata according to experimental results. We find that the chirality is initially determined by the nature of the asymmetric growth along the boundaries of enantiomeric high-index planes. The deep learning-based interpretation of chiral morphogenesis provides a theoretical understanding but also allows us to predict an unprecedented crossover pathway and the resulting morphology.
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BACKGROUND: Adiponectin (ADPN) plays a critical role in endocrine and cardiovascular functions, but traditional production methods, such as Escherichia coli and mammalian systems, have faced challenges in generating sufficiently active middle molecular weight (MMW) and high molecular weight (HMW) forms of recombinant human ADPN (hADPN). In our previous study, we proposed genome-edited chickens as an efficient platform for producing multimeric hADPN. However, the consistency of multimeric hADPN expression in this system across generations had not been further investigated. RESULTS: In this study, subsequent generations of ovalbumin (OVA) ADPN knock-in chickens showed stable multimeric hADPN production, yielding ~ 26% HMW ADPN (0.59 mg/mL) per hen. Comparative analysis revealed that egg white (EW)-derived hADPN predominantly consisted of hexameric and HMW forms, similar to serum-derived hADPN. In contrast, hADPN obtained from human embryonic kidney (HEK) 293 and High-Five (Hi-5) cells also exhibited the presence of trimers, indicating variability across different production systems. Furthermore, transcriptional expression analysis of ADPN multimerization-associated endoplasmic reticulum chaperone genes (Ero1-Lα, DsbA-L, ERP44, and PDI) indicated upregulation in the oviduct magnum of ADPN KI hens, suggesting the chicken oviduct magnum as the optimal site for HMW ADPN production. Lastly, the functional analysis demonstrated that EW-derived hADPN significantly reduced lipid droplets and downregulated lipid accumulation-related genes (LOX-1, AT1R, FAS, and FABP4) in human umbilical vein endothelial cells (HUVECs). CONCLUSION: In summary, stable and functional multimeric hADPN can be produced in genome-edited chickens even after generations. This highlights the potential of using chicken bioreactor for producing various high-value proteins.
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Robust ferroelectricity in HfO2-based ultrathin films has the potential to revolutionize nonvolatile memory applications in nanoscale electronic devices because of their compatibility with the existing Si technology. However, to fully exploit the potential of ferroelectric HfO2-based thin films, it is crucial to develop strategies for the controlled stabilization of various HfO2-based polymorphs in nanoscale heterostructures. This study demonstrates how substrate-orientation-induced anisotropic strain can engineer the crystal symmetry, structural domain morphology, and growth orientation of ultrathin Hf0.5Zr0.5O2 (HZO) films. Epitaxial ultrathin HZO films were grown on the heterostructures of (001)- and (110)-oriented La2/3Sr1/3MnO3/SrTiO3 (LSMO/STO) substrate. Various structural analyses revealed that the (110)-oriented substrate promotes a higher degree of structural order (crystallinity) with improved stability of the (111)-oriented orthorhombic phase (Pca21) of HZO. Conversely, the (001)-oriented substrate not only induces a distorted orthorhombic structure but also facilitates the partial stabilization of nonpolar phases. Electrical measurements revealed robust ferroelectric properties in epitaxial thin films without any wake-up effect, where the well-ordered crystal symmetry stabilized by STO(110) facilitated better ferroelectric characteristics. This study suggests that tuning the epitaxial growth of ferroelectric HZO through substrate orientation can improve the stability of the metastable ferroelectric orthorhombic phase and thereby offer a better understanding of device applications.
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ß-Glucan is an immunoenhancing agent whose biological activities are linked to molecular structure. On that basis, the polysaccharide can be physiochemically modified to produce valuable functional materials. This study investigated the physical properties and immunostimulatory activity of modified ß-glucan. Alkali-treated ß-glucan had a distinct shape and smaller particle size than untreated ß-glucan. The reduced particle size was conducive to the stability of the suspension because the ß-glucan appeared to be completely dissolved by this treatment, forming an amorphous mass. Furthermore, alkali treatment improved the immunostimulating activity of ß-glucan, whereas exposure of macrophages to heat-treated ß-glucan decreased their immune activity. ß-Glucan with reduced particle size by wet-grinding also displayed immunomodulatory activities. These results suggested that the particle size of ß-glucan is a key factor in ß-glucan-induced immune responses of macrophages. Thus, the modification of the ß-glucan particle size provides new opportunities for developing immunoenhancing nutraceuticals or pharmacological therapies in the future.
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Herein, a novel extracellular matrix (ECM) hydrogel is proposed fabricated solely from decellularized, human fibroblast-derived matrix (FDM) toward advanced wound healing. This FDM-gel is physically very stable and viscoelastic, while preserving the natural ECM diversity and various bioactive factors. Subcutaneously transplanted FDM-gel provided a permissive environment for innate immune cells infiltration. Compared to collagen hydrogel, excellent wound healing indications of FDM-gel treated in the full-thickness wounds are noticed, particularly hair follicle formation via highly upregulated ß-catenin. Sequential analysis of the regenerated wound tissues disclosed that FDM-gel significantly alleviated pro-inflammatory cytokine and promoted M2-like macrophages, along with significantly elevated vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) level. A mechanistic study demonstrated that macrophages-FDM interactions through cell surface integrins α5ß1 and α1ß1 resulted in significant production of VEGF and bFGF, increased Akt phosphorylation, and upregulated matrix metalloproteinase-9 activity. Interestingly, blocking such interactions using specific inhibitors (ATN161 for α5ß1 and obtustatin for α1ß1) negatively affected those pro-healing growth factors secretion. Macrophages depletion animal model significantly attenuated the healing effect of FDM-gel. This study demonstrates that the FDM-gel is an excellent immunomodulatory material that is permissive for host cells infiltration, resorbable with time, and interactive with macrophages, where it thus enables regenerative matrix remodeling toward a complete wound healing.
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Matriz Extracelular , Fibroblastos , Hidrogéis , Macrófagos , Cicatrização , Humanos , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Cicatrização/efeitos dos fármacos , Animais , Fibroblastos/metabolismo , Fibroblastos/efeitos dos fármacos , Matriz Extracelular/metabolismo , Camundongos , Modelos Animais de Doenças , MasculinoRESUMO
RNA nanotechnology, including rolling circle transcription (RCT), has gained increasing interest as a fascinating siRNA delivery nanoplatform for biostable and tumor-targetable RNA-based therapies. However, due to the lack of fine-tuning technologies for RNA nanostructures, the relationship between physicochemical properties and siRNA efficacy of polymeric siRNA nanoparticles (PRNs) with different sizes has not yet been fully elucidated. Herein, we scrutinized the effects of size/surface chemistry-tuned PRNs on the biological and physiological interactions with tumors. PRNs with adjusted size and surface properties were prepared using sequential engineering processes: RCT, condensation, and nanolayer deposition of functional biopolymers. Through the RCT process, nanoparticles of three sizes with a diameter of 50-200 nm were fabricated and terminated with three types of biopolymers: poly-l-lysine (PLL), poly-l-glutamate (PLG), and hyaluronic acid (HA) for different surface properties. Among the PRNs, HA-layered nanoparticles with a diameter of â¼200 nm exhibited the most effective systemic delivery, resulting in superior anticancer effects in an orthotopic breast tumor model due to the CD44 receptor targeting and optimized nanosized structure. Depending on the type of PRNs, the in vivo siRNA delivery with protein expression inhibition differed by up to approximately 20-fold. These findings indicate that the types of layered biopolymers and the PRNs size mediate efficient polymeric siRNA delivery to the targeted tumors, resulting in high RNAi-induced therapeutic efficacy. This RNA-nanotechnology-based size/surface editing can overcome the limitations of siRNA therapeutics and represents a potent built-in module method to design RNA therapeutics tailored for targeted cancer therapy.
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Nanopartículas , Neoplasias , Distribuição Tecidual , Linhagem Celular Tumoral , RNA Interferente Pequeno/genética , Nanopartículas/química , Polímeros/metabolismo , Biopolímeros/metabolismo , Neoplasias/tratamento farmacológicoRESUMO
OBJECTIVE: The Montreal Cognitive Assessment (MoCA) is recommended for general cognitive evaluation in Parkinson's disease (PD) patients. However, age- and education-adjusted cutoffs specifically for PD have not been developed or systematically validated across PD cohorts with diverse education levels. METHODS: In this retrospective analysis, we utilized data from 1,293 Korean patients with PD whose cognitive diagnoses were determined through comprehensive neuropsychological assessments. Age- and education-adjusted cutoffs were formulated based on 1,202 patients with PD. To identify the optimal machine learning model, clinical parameters and MoCA domain scores from 416 patients with PD were used. Comparative analyses between machine learning. METHODS: and different cutoff criteria were conducted on an additional 91 consecutive patients with PD. RESULTS: The cutoffs for cognitive impairment decrease with increasing age within the same education level. Similarly, lower education levels within the same age group correspond to lower cutoffs. For individuals aged 60-80 years, cutoffs were set as follows: 25 or 24 years for those with more than 12 years of education, 23 or 22 years for 10-12 years, and 21 or 20 years for 7-9 years. Comparisons between age- and education-adjusted cutoffs and the machine learning method showed comparable accuracies. The cutoff method resulted in a higher sensitivity (0.8627), whereas machine learning yielded higher specificity (0.8250). CONCLUSION: Both the age- and education-adjusted cutoff. METHODS: and machine learning. METHODS: demonstrated high effectiveness in detecting cognitive impairment in PD patients. This study highlights the necessity of tailored cutoffs and suggests the potential of machine learning to improve cognitive assessment in PD patients.
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Every year, the overprescription, misuse, and improper disposal of antibiotics have led to the rampant development of drug-resistant pathogens and, in turn, a significant increase in the number of patients who die of drug-resistant fungal infections. Recently, researchers have begun investigating the use of antimicrobial peptides (AMPs) as next-generation antifungal agents to inhibit the growth of drug-resistant fungi. The antifungal activity of alpha-helical peptides designed using the cationic amino acids containing lysine and arginine and the hydrophobic amino acids containing isoleucine and tryptophan were evaluated using 10 yeast and mold fungi. Among these peptides, WIK-14, which is composed of a 14-mer with tryptophan sequences at the amino terminus, showed the best antifungal activity via transient pore formation and ROS generation. In addition, the in vivo antifungal effects of WIK-14 were investigated in a mouse model infected with drug-resistant Candida albicans. The results demonstrate the potential of AMPs as antifungal agents.
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Antifúngicos , Triptofano , Camundongos , Animais , Humanos , Antifúngicos/farmacologia , Antifúngicos/química , Triptofano/química , Lisina/química , Peptídeos Antimicrobianos , Peptídeos Catiônicos Antimicrobianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/química , Aminoácidos/farmacologia , Candida albicans , Arginina/química , Testes de Sensibilidade MicrobianaRESUMO
Repeated pandemics caused by the influenza virus and severe acute respiratory syndrome coronavirus (SARS-CoV) have resulted in serious problems in global public health, emphasizing the need for broad-spectrum antiviral therapeutics against respiratory virus infections. Here, we show the protective effects of long-acting recombinant human interleukin-7 fused with hybrid Fc (rhIL-7-hyFc) against major respiratory viruses, including influenza virus, SARS-CoV-2, and respiratory syncytial virus. Administration of rhIL-7-hyFc in a therapeutic or prophylactic regimen induces substantial antiviral effects. During an influenza A virus (IAV) infection, rhIL-7-hyFc treatment increases pulmonary T cells composed of blood-derived interferon γ (IFNγ)+ conventional T cells and locally expanded IL-17A+ innate-like T cells. Single-cell RNA transcriptomics reveals that rhIL-7-hyFc upregulates antiviral genes in pulmonary T cells and induces clonal expansion of type 17 innate-like T cells. rhIL-7-hyFc-mediated disease prevention is dependent on IL-17A in both IAV- and SARS-CoV-2-infected mice. Collectively, we suggest that rhIL-7-hyFc can be used as a broadly active therapeutic for future respiratory virus pandemic.
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Influenza Humana , Interleucina-17 , Animais , Camundongos , Humanos , Interleucina-17/genética , Interleucina-7 , Linfócitos T , SARS-CoV-2 , Influenza Humana/tratamento farmacológico , Antivirais/farmacologia , Antivirais/uso terapêuticoRESUMO
Layered 2D transition metal dichalcogenides (TMDs) have been suggested as efficient substitutes for Pt-group metal electrocatalysts in the hydrogen evolution reaction (HER). However, poor catalytic activities in neutral and alkaline electrolytes considerably hinder their practical applications. Furthermore, the weak adhesion between TMDs and electrodes often impedes long-term durability and thus requires a binder. Here, a universal platform is reported for robust dual-atom doped 2D electrocatalysts with superior HER performance over a wide pH range media. V:Co-ReS2 on a wafer scale is directly grown on oxidized Ti foil by a liquid-phase precursor-assisted approach and subsequently used as highly efficient electrocatalysts. The catalytic performance surpasses that of Pt group metals in a high current regime (≥ 100 mA cm-2) at pH ≥ 7, with a high durability of more than 70 h in all media at 200 mA cm-2. First-principles calculations reveal that V:Co dual doping in ReS2 significantly reduces the water dissociation barrier and simultaneously enables the material to achieve the thermoneutral Gibbs free energy for hydrogen adsorption.
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Objective: "SIGnature Libraries" channel the dynamism of academic society-based special interest groups (SIG) to systematically identify and provide user-oriented access to essential literature for a subspecialty field in a manner that keeps pace with the field's continuing evolution. The libraries include literature beyond clinical trial data to encompass historical context, diagnostic conceptualization, and community organization materials to foster a holistic understanding of how neurologic conditions affect individuals, their community, and their lived experience. Methods: Utilizing a modified-Delphi approach, Child Neurology Society's Cerebral Palsy (CP) SIG (n = 75) administered two rounds of literature submissions and ratings. A final review by an 11-member international advisory group determined threshold ratings for resource inclusion and the library's final structure. Results: Seventy-nine articles were submitted for the first Delphi round and 22 articles for the second Delphi round. Survey response rates among SIG members were 29/75 for the first round and 24/75 for the second round. The advisory board added additional articles in the final review process in view of the overall project goal. A total of 60 articles were included in the final library, and articles were divided into seven sections and stratified by rating scores. A process for ongoing revisions of the library was determined. The library will be published on the Child Neurology Society website and made publicly accessible. Conclusions: The CP SIGnature Library offers learners an unprecedented resource that provides equitable access to latest consensus guidelines, existing seminal datasets, up-to-date review articles, and other patient care tools. A distinctive feature of the library is its intentional large scope and depth, presented in a stratified fashion relative to the consensus-determined importance of each article. Learners can efficiently navigate the library based on individual interests and goals, and the library can be used as core curriculum for CP education.
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The realm of antimicrobial proteins in plants is extensive but remains relatively uncharted. Understanding the mechanisms underlying the action of plant antifungal proteins (AFPs) holds promise for antifungal strategies. This study aimed to bridge this knowledge gap by comprehensively screening Arabidopsis thaliana species to identify novel AFPs. Using MALDI-TOF analysis, we identified a member of the TEOSINTE BRANCHED1/CYCLOIDEA/PROLIFERATING CELL FACTOR1 (TCP) family of transcription factors as a novel AFP, A. thaliana TCP21 (AtTCP21; accession number NP_196450). Bacterially purified recombinant AtTCP21 inhibited the growth of various pathogenic fungal cells. AtTCP21 was more potent than melittin, a well-known AFP, in combating Colletotrichum gloeosporioides. Growth inhibition assays against various fungal pathogens and yeasts confirmed the pH-dependent antimicrobial activity of AtTCP21. Without inducing any membrane alterations, AtTCP21 penetrates the fungal cell wall and membrane, where it instigates a repressive milieu for fungal cell growth by generating intracellular reactive oxygen species and mitochondrial superoxides; resulting in morphological changes and apoptosis. Our findings demonstrate the redox-regulating effects of AtTCP21 and point to its potential as an antimicrobial agent.