Microstructural Evolution, Hardness and Wear Resistance of WC-Co-Ni Composite Coatings Fabricated by Laser Cladding.

This study investigated how process parameters of laser cladding affect the microstructure and mechanical properties of WC-12Co composite coating for use as a protective layer of continuous caster rolls. WC-Co powders, WC-Ni powders, and Ni-Cr alloy powder with various wear resistance characteristics were evaluated in order to determine their applicability for use as cladding materials for continuous caster roll coating. The cladding process was conducted with various parameters, including laser powers, cladding speeds, and powder feeding rates, then the phases, microstructure, and micro-hardness of the cladding layer were analyzed in each specimen. Results indicate that, to increase the hardness of the cladding layer in WC-Co composite coating, the dilution of the cladding layer by dissolution of Fe from the substrate should be minimized, and the formation of the Fe-Co alloy phase should be prevented. The mechanical properties and wear resistance of each powder with the same process parameters were compared and analyzed. The microstructure and mechanical properties of the laser cladding layer depend not only on the process parameters, but also on the powder characteristics, such as WC particle size and the type of binder material. Additionally, depending on the degree of thermal decomposition of WC particles and evolution of W distribution within the cladding layer, the hardness of each powder can differ significantly, and the wear mechanism can change.

Making the Brightest Ones Dim: Maximizing the Photothermal Conversion Efficiency of BODIPY-Based Photothermal Agents.

The successful implementation of photothermal therapy (PTT) in cancer treatment hinges on the development of highly effective photothermal agents (PTAs). Boron dipyrromethene (BODIPY) dyes, being well known for their high brightness and quantum efficiencies, are the antithesis of PTAs. Nonetheless, a systematic exploration of the photophysics and photothermal characteristics of a series of π-extended BODIPY dyes with high absorptivity in the near-infrared (NIR) region has achieved superior photothermal conversion efficiencies (>90%), in both monomeric state and nanoparticles after encapsulation in a biocompatible polyethyleneglycol 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy-(polyethylene glycol)-2000]. Optimal PTA candidates combine strong NIR absorption provided by extended donor-acceptor conjugation and an optimization of the electronic and steric effects of meso-substituents to maximize photothermal conversion performance. The PTT-optimized meso-CF3-BODIPY, TCF3PEn exhibits exceptional efficacy in inducing cancer cell apoptosis and in vivo tumor ablation using low-power NIR laser irradiation (0.3 W cm-2, 808 nm) as well as excellent biological safety, underscoring its potential for advancing light-induced cancer therapies.

Intravenous immunoglobulin resistance in Kawasaki disease patients: prediction using clinical data.

BACKGROUND: About 10-20% of Kawasaki disease (KD) patients are resistant to the initial infusion of intravenous immunoglobin (IVIG). The aim of this study was to assess whether IVIG resistance in KD patients could be predicted using standard clinical and laboratory features. METHODS: Data were from two cohorts: a Korean cohort of 7101 KD patients from 2015 to 2017 and a cohort of 649 KD patients from San Diego enrolled from 1998 to 2021. Features included laboratory values, the worst Z-score from the initial echocardiogram or during hospitalization, and the five clinical KD signs at presentation. RESULTS: Five machine learning models achieved a maximum median AUC of 0.711 [IQR: 0.706-0.72] in the Korean cohort and 0.696 [IQR: 0.609-0.722] in the San Diego cohort during stratified 10-fold cross-validation using significant laboratory features identified from univariate analysis. Adding the Z-score, KD clinical signs, or both did not considerably improve the median AUC in either cohort. CONCLUSIONS: Using commonly measured clinical laboratory data alone or in conjunction with echocardiographic findings and clinical features is not sufficient to predict IVIG resistance. Further attempts to predict IVIG resistance will need to incorporate additional data such as transcriptomics, proteomics, and genetics to achieve meaningful predictive utility. IMPACT: We demonstrated that laboratory, echocardiographic, and clinical findings cannot predict intravenous immunoglobin (IVIG) resistance to a clinically meaningful extent using machine learning in a homogenous Asian or ethnically diverse population of patients with Kawasaki disease (KD). Visualizing these features using uniform manifold approximation and projection (UMAP) is an important step to evaluate predictive utility in a qualitative manner. Further attempts to predict IVIG resistance in KD patients will need to incorporate novel biomarkers or other specialized features such as genetic differences or transcriptomics to be clinically useful.

Trend of fetal echocardiography use and comparison of medical costs for congenital heart disease treatment based on fetal echocardiography use in a Korean single center.

Background: The rate of the prenatal diagnosis of congenital heart disease is increasing along with advances in fetal echocardiography techniques. Here, we aimed to investigate the trend of the use of fetal echocardiography over time and to compare the medical costs of congenital heart disease treatment according to whether fetal echocardiography was performed. Methods: We reviewed our hospital's database, and patients who underwent the first surgery for congenital heart disease within 30 days of birth during 2005-2007, 2011-2013, and 2017-2019 were included. The severity of congenital heart disease diagnosed in each case was evaluated according to The Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery Congenital Heart Surgery Mortality Scores (STS-EACTS Mortality Scores) and Mortality Categories (STAT Mortality Categories). Results: In total, 375 patients were analyzed, and fetal echocardiography use increased significantly after the 2010s compared with in 2005-2007 (19.1% vs. 39%, p = 0.032 in Mortality Category 1-3; 15.5% vs. 69.5%, p = 0.000 in Mortality Category 4-5). Additionally, the mean STS-EACTS Mortality Score was higher in prenatally diagnosed patients than in postnatally diagnosed patients (2.287 vs. 1.787, p = 0.001). In the recent period, there was no significant difference in hospitalization durations and medical costs according to whether or not fetal echocardiography was performed. Conclusions: This single center study showed the use of fetal echocardiography is increasing. Further, prenatal diagnosis with fetal echocardiography causing no differences in medical costs in recent years. Therefore, we suggest that fetal echocardiography can be applied more widely without increasing the economic burden.

Genetically Stable and Scalable Nanoengineering of Human Primary T Cells via Cell Mechanoporation.

Effective tumor regression has been observed with chimeric antigen receptor (CAR) T cells; however, the development of an affordable, safe, and effective CAR-T cell treatment remains a challenge. One of the major obstacles is that the suboptimal genetic modification of T cells reduces their yield and antitumor activity, necessitating the development of a next-generation T cell engineering approach. In this study, we developed a nonviral T cell nanoengineering system that allows highly efficient delivery of diverse functional nanomaterials into primary human T cells in a genetically stable and scalable manner. Our platform leverages the unique cell deformation and restoration process induced by the intrinsic inertial flow in a microchannel to create nanopores in the cellular membrane for macromolecule internalization, leading to effective transfection with high scalability and viability. The proposed approach demonstrates considerable potential as a practical alternative technique for improving the current CAR-T cell manufacturing process.

Anaerobic digestion of sewage sludge using anaerobic dynamic membrane bioreactor under various sludge composition and organic loading rates.

This study investigates the effects of sludge compositions and organic loading rates (OLRs) on stable biogas production during sludge digestion. Batch digestion experiments evaluate the effects of alkaline-thermal pretreatment and waste activated sludge (WAS) fractions on the biochemical methane potential (BMP) of sludge. A lab-scale anaerobic dynamic membrane bioreactor (AnDMBR) is fed with a mixture of primary sludge and pretreated WAS. Monitoring of volatile fatty acid to total alkalinity (FOS/TAC) helps maintain operational stability. The highest average methane production rate of 0.7 L/L·d is achieved when the OLR, hydraulic retention time, WAS volume fraction, and FOS/TAC ratio are 5.0 g COD/L·d, 12 days, 0.75, and 0.32, respectively. This study finds functional redundancy in two pathways: hydrogenotrophic and acetolactic. An increase in OLR promotes bacterial and archaeal abundance and specific methanogenic activity. These results can be applied to the design and operation of sludge digestion for stable, high-rate biogas recovery.

Carbamate JNK3 Inhibitors Show Promise as Effective Treatments for Alzheimer's Disease: In Vivo Studies on Mouse Models.

We have been developing new inhibitors for c-Jun N-terminal kinase 3 (JNK3) as a potential treatment for Alzheimer's disease (AD). We identified potential JNK3 inhibitors through pharmacodynamic optimization studies, including benzimidazole compounds 2 and 3, but their unreliable pharmacokinetic properties led us to develop carbamate inhibitors 2h and 3h. In vitro studies validated carbamate inhibitors 2h and 3h as potent and highly selective JNK3 inhibitors with favorable pharmacokinetic profiles. Oral administration of 2h and 3h to both APP/PS1 and 3xTg AD mouse models improved cognitive function, indicating their potential as effective treatments for Alzheimer's disease. Carbamate JNK3 inhibitor 3h, in particular, restored cognitive function to near-normal levels in the 3xTg mice model of AD and led to pTau reduction in the hippocampal tissues of 3xTg-AD mice during in vivo behavioral evaluations. We intend to further develop these carbamate JNK3 inhibitors in preclinical studies as a potential first-in-class treatment for AD.

Proteogenomic landscape of human pancreatic ductal adenocarcinoma in an Asian population reveals tumor cell-enriched and immune-rich subtypes.

We report a proteogenomic analysis of pancreatic ductal adenocarcinoma (PDAC). Mutation-phosphorylation correlations identified signaling pathways associated with somatic mutations in significantly mutated genes. Messenger RNA-protein abundance correlations revealed potential prognostic biomarkers correlated with patient survival. Integrated clustering of mRNA, protein and phosphorylation data identified six PDAC subtypes. Cellular pathways represented by mRNA and protein signatures, defining the subtypes and compositions of cell types in the subtypes, characterized them as classical progenitor (TS1), squamous (TS2-4), immunogenic progenitor (IS1) and exocrine-like (IS2) subtypes. Compared with the mRNA data, protein and phosphorylation data further classified the squamous subtypes into activated stroma-enriched (TS2), invasive (TS3) and invasive-proliferative (TS4) squamous subtypes. Orthotopic mouse PDAC models revealed a higher number of pro-tumorigenic immune cells in TS4, inhibiting T cell proliferation. Our proteogenomic analysis provides significantly mutated genes/biomarkers, cellular pathways and cell types as potential therapeutic targets to improve stratification of patients with PDAC.

The effects of ammonia acclimation on biogas recovery and the microbial population in continuous anaerobic digestion of swine manure.

This study investigated the ammonia toxicity and the acclimation of anaerobic microbiome in continuous anaerobic digestion of swine manure using unacclimated inoculum. When the total ammonia nitrogen concentration (TAN) reached 2.5 g N/L, the methane yield decreased from 254.1 ± 9.6 to 154.6 ± 9.9 mL/g COD. The free ammonia nitrogen concentration of the inhibited condition was 190 mg N/L. The methane yield was eventually recovered as 269.6 ± 3.6 mL/g COD with a further operation. Anaerobic toxicity assay (ATA) showed that mixed liquor from the recovered phase possessed enhanced tolerance to ammonia, not only within the exposed level in continuous operation (<2.5 g NH3/L) but also over the range (>2.5 g NH3/L). Microbial analysis revealed that continuous operation under ammonia stress resulted in the change of both bacterial and archaeal populations. The ammonia adaptation was concurrent with the archaeal population shift from Methanosaeta to Methanosarcina and Methanobacterium. The dominancy of Clostridia in bacterial population was found in the recovered phase. It is highly recommended to use an inoculum acclimated to a target ammonia level which can be pre-checked by ATA and to secure a start-up period for ammonia adaptation in the field application of anaerobic digestion for swine manure.

Biohydrogen and biomethane production from food waste using a two-stage dynamic membrane bioreactor (DMBR) system.

This study examined a two-stage dynamic membrane bioreactor (DMBR) system for biohydrogen and biomethane production from food waste (FW) in mesophilic condition. The two-stage DMBR system enabled high-rate H2 and CH4 production from particulate feedstock by enhanced microorganism retention. Chemical energy in FW was recovered up to 79% as renewable energy. The highest average hydrogen production rate of 7.09 ± 0.42 L/L-d was observed at a hydraulic retention time (HRT) of 8 h in the H2-DMBR, while the highest CH4 average production rate of 0.99 ± 0.02 L/L-d was observed at an HRT of 6 d in the CH4-DMBR. The high specific methanogenic activity of 71.7 mL CH4/g VSS-d was maintained at the short HRT, which also contributed to the high MPR. The genus Clostridium was dominant in the H2-DMBR, while bacterial and archaeal populations in the CH4-DMBR were dominated by the class Clostridia and genera Methanobacterium and Methanosaeta, respectively.

Sludge disintegration and anaerobic digestion enhancement by alkaline-thermal pretreatment: Economic evaluation and microbial population analysis.

Alkaline-thermal pretreatment was examined for waste activated sludge (WAS) disintegration and subsequent anaerobic digestion (AD). Pretreatment at 60 °C was estimated to provide better economic benefits than higher temperature conditions. The maximum methane yield of 215.6 mL/g COD was achieved when WAS was pretreated at 60 °C and pH 10 for 24 h, which was 46.6% higher than untreated WAS. The pretreatment condition also provided the maximum net savings. The degree of sludge disintegration, considering both loosely bound-extracellular polymeric substance and soluble COD, would be a better indicator to predict anaerobic digestibility than the solubilization rate that considers soluble COD alone. Microbial analysis implied that pretreatment facilitated the growth of hydrolytic bacteria, phyla Bacteroidetes and Firmicutes. In addition, sludge pretreatment enhanced the growth of both acetoclastic and hydrogenotrophic methanogens, genera Methanosaeta and Methanobacterium. The mild AT-PT would be useful to enhance the digestion performance and economic benefit of WAS digestion.

Biofilm formation as a method of improved treatment during anaerobic digestion of organic matter for biogas recovery.

The efficiency of anaerobic digestion could be increased by promoting microbial retention through biofilm development. The inclusion of certain types of biofilm carriers has differentiated existing AD biofilm reactors through their respective mode of biofilm growth. Bacteria and archaea engaged in methanogenesis during anaerobic processes potentially build biofilms by adhering or attaching to biofilm carriers. Meta-analyzed results depicted varying degrees of biogas enhancement within AD biofilm reactors. Furthermore, different carrier materials highly induced the dynamicity of the dominant microbial population in each system. It is suggested that the promotion of surface contact and improvement of interspecies electron transport have greatly impacted the treatment results. Modern spectroscopy techniques have been and will continue to give essential information regarding biofilm's composition and structural organization which can be useful in elucidating the added function of this special layer of microbial cells.

Effect of low-thermal pretreatment on the methanogenic performance and microbiome population of continuous high-solid anaerobic digester treating dewatered sludge.

Undigested and dewatered sludge at 10% total solids was pretreated at 60 °C for 3 h and fed to a lab-scale horizontal anaerobic bioreactor for 130 days with solids retention time (SRTs) from 25 to 16 d. The low-thermal pretreatment enabled higher net energy production, improved sludge treatment efficiency, and enhanced digestion stability. The highest average biomethane yield and production rate were 138.5 mL/g VS and 0.43 L/L.d, respectively, and the economic benefit was expected to be the maximum at SRT 16 d. Pretreatment did not increase the specific methanogenic activity per unit methanogen, but resulted in higher abundance of methanogenic archaea and hydrolytic bacteria. Methanogenic population shifted from hydrogenotrophic to acetoclastic, consistent with predicted gene expression at SRT equal or below 20 d. Anaerobic digestion along with low-thermal could be a feasible management strategy for undigested dewatered sludge from small WWTPs.

Highly Efficient Transfection of Human Primary T Lymphocytes Using Droplet-Enabled Mechanoporation.

Whole-cell-based therapy has been extensively used as an effective disease treatment approach, and it has rapidly changed the therapeutic paradigm. To fully accommodate this shift, advances in genome modification and cell reprogramming methodologies are critical. Traditionally, molecular tools such as viral and polymer nanocarriers and electroporation have been the norm for internalizing external biomolecules into cells for cellular engineering. However, these approaches are not fully satisfactory considering their cytotoxicity, high cost, low scalability, and/or inconsistent and ineffective delivery and transfection. To address these challenges, we present an approach that leverages droplet microfluidics with cell mechanoporation, bringing intracellular delivery to the next level. In our approach, cells and external cargos such as mRNAs and plasmid DNAs are coencapsulated into droplets, and as they pass through a series of narrow constrictions, the cell membrane is mechanically permeabilized where the cargos in the vicinity are internalized via convective solution exchange enhanced by recirculation flows developed in the droplets. Using this principle, we demonstrated a high level of functional macromolecule delivery into various immune cells, including human primary T cells. By utilizing droplets, the cargo consumption was drastically reduced, and near-zero clogging was realized. Furthermore, high scalability without sacrificing cell viability and superior delivery over state-of-the-art methods and benchtop techniques were demonstrated. Notably, the droplet-based intracellular delivery strategy presented here can be further applied to other mechanoporation microfluidic techniques, highlighting its potential for cellular engineering and cell-based therapies.

Enhanced anaerobic digestion of waste-activated sludge via bioaugmentation strategy-Phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt2) analysis through hydrolytic enzymes and possible linkage to system performance.

In this study, anaerobic digestion of waste-activated sludge was bioaugmented with hydrolytic bacteria, Bacteroidetes uniformis (Bacteroidetes, B) and Clostridium sp. (Firmicutes, F) at various dosages. Bioaugmentation resulted in enhanced methane conversion of waste-activated sludge. The highest methane yield of 298.1 mL CH4/g-COD, 85.2% COD conversion efficiency was obtained when Bacteroidetes uniformis and Clostridium sp. were augmented at 100 and 900 CFU/mL, respectively. The microbial community analysis demonstrated that bioaugmentation increased the proportion of Bacteroidetes, Firmicutes, and Proteobacteria. Furthermore, at the highest methane yield, the principal methanogenic pathway was altered from acetoclastic to a mixture of hydrogenotrophic and acetoclastic; the major species shifted from Methanosaeta concilii to Methanobacterium subterraneum. Predicted gene analysis revealed that increased expression of hydrolases resulted in enhanced methane conversion through bioaugmentation.

Biopolymer production using volatile fatty acids as resource: Effect of feast-famine strategy and lignin reinforcement.

The present study aimed to investigate the biopolymer production using VFA's as carbon source through feast and famine strategy in a sequencing batch reactor. Famine condition with nutrients and oxygen limitation resulted in high polyhydroxybutyrate yield (PHB: 2.65 ± 0.012 g/L; 0.36 ± 0.015 gPHB/gVFA) than feast mode (0.26 ± 0.02 g/L; 0.034 ± 0.013 gPHB/gVFA). Repeated batch operations induced substrate consumption, wherein acetate utilization was high in both the conditions (feast: 83%, famine 74%) followed by butyrate (feast: 74%, famine 72%). Besides, high biomass concentration was also observed in feast condition (3.45 ± 0.14 g/L VSS), while oxygen and nutrients limitation in famine mode regulated the carbon use for biomass growth (2.46 ± 0.15 g/L VSS). Further, PHB grafting with lignin (3% and 5%) exhibited increased thermal stability than pristine PHB. Biopolymer production using VFA's as carbon source and utilization of lignin as functional filler for strengthening PHB offer lignin valorization also wider its applications specifically in the biomedical field.

A child with spontaneous recovery of normal sinus rhythm from idiopathic complete atrioventricular block.

Atrioventricular block in children is not common but is a life-threatening disease. As no spontaneous regression of conductive disruption was reported, those sustaining idiopathic atrioventricular blocks are difficult to manage and often require pacemaker implantation. In this study, we presented the first case of a child who surprisingly recovered from idiopathic complete atrioventricular block without intervention 4 years after initial presentation.

PHF7 Modulates BRDT Stability and Histone-to-Protamine Exchange during Spermiogenesis.

Spermatogenesis is a complex process of sperm generation, including mitosis, meiosis, and spermiogenesis. During spermiogenesis, histones in post-meiotic spermatids are removed from chromatin and replaced by protamines. Although histone-to-protamine exchange is important for sperm nuclear condensation, the underlying regulatory mechanism is still poorly understood. Here, we identify PHD finger protein 7 (PHF7) as an E3 ubiquitin ligase for histone H3K14 in post-meiotic spermatids. Generation of Phf7-deficient mice and Phf7 C160A knockin mice with impaired E3 ubiquitin ligase activity reveals defects in histone-to-protamine exchange caused by dysregulation of histone removal factor Bromodomain, testis-specific (BRDT) in early condensing spermatids. Surprisingly, E3 ubiquitin ligase activity of PHF7 on histone ubiquitination leads to stabilization of BRDT by attenuating ubiquitination of BRDT. Collectively, our findings identify PHF7 as a critical factor for sperm chromatin condensation and contribute to mechanistic understanding of fundamental phenomenon of histone-to-protamine exchange and potential for drug development for the male reproduction system.

Changes of hospitalization trend in the pediatric cardiology division of a single center by increasing adult with congenital heart disease.

BACKGROUND: As a result of advances in pediatric care and diagnostic testing, there is a growing population of adults with congenital heart disease (ACHD). The purpose of this study was to better define the epidemiology and changes in the trend of hospitalizations for ACHD in Korean society. METHODS: We reviewed outpatient and inpatient data from 2005 to 2017 to identify patient ≥18 years of age admitted for acute care with a congenital heart disease (CHD) diagnosis in the pediatric cardiology division. We tried to analyze changes of hospitalization trend for ACHD. RESULTS: The ratio of outpatients with ACHD increased 286.5%, from 11.1% (1748/15,682) in 2005 to 31.8% (7795/24,532) in 2017. The number of ACHD hospitalizations increased 360.7%, from 8.9% (37/414) in 2005 to 32.1% (226/705) in 2017. The average patient age increased from 24.3 years in 2005 to 27.4 in 2017. The main diagnosis for admission of ACHD is heart failure, arrhythmia and Fontan-related complications. The annual ICU admission percentage was around 5% and mean length of intensive care unit (ICU) stay was 8.4 ± 14.6 days. Mean personal hospital charges by admission of ACHD increased to around two times from 2005 to 2017. (from $2578.1 to $3697.0). Total annual hospital charges by ACHD markedly increased ten times (from $95,389.7 to $831,834.2). CONCLUSIONS: The number of hospital cares for ACHD dramatically increased more than five times from 2005 to 2017. We need preparations for efficient healthcare for adults with CHD such as a multi-dimensional approach, effective communication, and professional training.