Alloying and confinement effects on hierarchically nanoporous CuAu for efficient electrocatalytic semi-hydrogenation of terminal alkynes.

Electrocatalytic alkynes semi-hydrogenation to produce alkenes with high yield and Faradaic efficiency remains technically challenging because of kinetically favorable hydrogen evolution reaction and over-hydrogenation. Here, we propose a hierarchically nanoporous Cu50Au50 alloy to improve electrocatalytic performance toward semi-hydrogenation of alkynes. Using Operando X-ray absorption spectroscopy and density functional theory calculations, we find that Au modulate the electronic structure of Cu, which could intrinsically inhibit the combination of H* to form H2 and weaken alkene adsorption, thus promoting alkyne semi-hydrogenation and hampering alkene over-hydrogenation. Finite element method simulations and experimental results unveil that hierarchically nanoporous catalysts induce a local microenvironment with abundant K+ cations by enhancing the electric field within the nanopore, accelerating water electrolysis to form more H*, thereby promoting the conversion of alkynes. As a result, the nanoporous Cu50Au50 electrocatalyst achieves highly efficient electrocatalytic semi-hydrogenation of alkynes with 94% conversion, 100% selectivity, and a 92% Faradaic efficiency over wide potential window. This work provides a general guidance of the rational design for high-performance electrocatalytic transfer semi-hydrogenation catalysts.

Asymmetric Local Electric Field Induced by Dual Heteroatoms on Copper Boosts Efficient CO2 Reduction Over Ultrawide Potential Window.

Electrocatalytic reduction of CO2 powered by renewable electricity provides an elegant route for converting CO2 into valuable chemicals and feedstocks, but normally suffers from a high overpotential and low selectivity. Herein, Ag and Sn heteroatoms were simultaneously introduced into nanoporous Cu (np-Ag/Sn-Cu) mainly in the form of an asymmetric local electric field for CO2 electroreduction to CO in an aqueous solution. The designed np-Ag/Sn-Cu catalyst realizes a recorded 90% energy efficiency and a 100% CO Faradaic efficiency over ultrawide potential window (ΔE = 1.4 V), outperforming state-of-the-art Au and Ag-based catalysts. Density functional theory calculations combined with in situ spectroscopy studies reveal that Ag and Sn heteroatoms incorporated into Cu matrix could generate strong and asymmetric local electric field, which promotes the activation of CO2 molecules, enhances the stabilization of the *COOH intermediate, and suppresses the hydrogen evolution reaction, thus favoring the production of CO during CO2RR.

Defect Engineered Bi2Te3 Nanosheets with Enhanced Haloperoxidase Activity for Marine Antibiofouling.

Defective bismuth telluride (Bi2Te3) nanosheets, an artificial nanozyme mimicking haloperoxidase activity (hPOD), show promise as eco-friendly, bactericidal, and antimicrofouling materials by enhancing cytotoxic hypohalous acid production from halides and H2O2. Microscopic and spectroscopic characterization reveals that controlled NaOH (upto X = 250 µL) etching of the nearly inactive non-transition metal chalcogenide Bi2Te3 nanosheets creates controlled defects (d), such as Bi3+species, in d-Bi2Te3-X that induces enhanced hPOD activity. d-Bi2Te3-250 exhibits approximately eight-fold improved hPOD than the as-grown Bi2Te3 nanosheets. The antibacterial activity of d-Bi2Te3-250 nanozymes, studied by bacterial viability, show 1, and 45% viability for Staphylococcus aureus and Pseudomonas aeruginosa, respectively, prevalent in marine environments. The hPOD mechanism is confirmed using scavengers, implicating HOBr and singlet oxygen for the effect. The antimicrofouling property of the d-Bi2Te3-250 nanozyme has been studied on Pseudomonas aeruginosa biofilm in a lab setting by multiple assays, and also on titanium (Ti) plates coated with the nanozyme mixed commercial paint, exposed to seawater in a real setting. All studies, including direct microscopic evidence, exhibit inhibition of microfouling, up to ≈73%, in the presence of nanozymes. This approach showcases that defect engineering can induce antibacterial, and antimicrofouling activity in non-transition metal chalcogenides, offering an inexpensive alternative to noble metals.

Tuning Crystal Phase of Palladium-Selenium Nanowires for Enhanced Ethylene Glycol Electrocatalytic Oxidation.

Alcohol electrooxidation is pivotal for a sustainable energy economy. However, designing efficient electrocatalysts for this process is still a formidable challenge. Herein, palladium-selenium nanowires featuring distinct crystal phases: monoclinic Pd7Se2 and tetragonal Pd4.5Se for ethylene glycol electrooxidation reaction (EGOR) are synthesized. Notably, the supported monoclinic Pd7Se2 nanowires (m-Pd7Se2 NWs/C) exhibit superior EGOR activity, achieving a mass activity (MA) and specific activity (SA) of 10.4 A mgPd -1 (18.7 mA cm-2), which are 8.0 (6.7) and 10.4 (8.2) times versus the tetragonal Pd4.5Se and commercial Pd/C and surpass those reported in the literature. Furthermore, m-Pd7Se2 NWs/C displays robust catalytic activity for other alcohol electrooxidation. Comprehensive characterization and density functional theory (DFT) calculations reveal that the enhanced electrocatalytic performance is attributed to the increased formation of Pd0 on the high-index facets of the m-Pd7Se2 NWs, which lowers the energy barriers for the C─C bond dissociation in CHOHCHOH* and the CO* oxidation to CO2*. This study provides palladium-based alloy electrocatalysts exhibiting the highest mass activity reported to date for the electrooxidation of ethylene glycol, achieved through the crystalline phase engineering strategy.

Design and synthesis of versatile ligand precursors based on phosphonium ylides for palladalactam formation and catalytic investigation.

A new series of ligand precursors designed for the synthesis of palladalactams has been developed. These precursors are easily accessible through a one-step reaction involving 2-chloro-N-phenylacetamide and a wide choice of various monophosphines, offering tunable electronic and steric properties within the ligand framework. The stability of both ligand precursors and resulting palladalactams in ambient air enhances their practical applicability. A newly synthesized palladalactam, featuring an electron-donating triethylphosphine moiety on the anionic phosphonium ylide ligand scaffold exhibited promising catalytic activities in the Mizoroki-Heck coupling reaction between aryl chlorides and alkenes. Theoretical calculations further affirmed that the ligand system in the complex is the most electron-donating, forming the strongest Pd-C bond compared to other complexes with alternative phosphine moieties.

Implementation of a Real-Time Documentation Assistance Tool: Automated Diagnosis (AutoDx).

BACKGROUND: Clinical documentation improvement programs are utilized by most health care systems to enhance provider documentation. Suggestions are sent to providers in a variety of ways, and are commonly referred to as coding queries. Responding to these coding queries can require significant provider time and do not often align with workflows. To enhance provider documentation in a more consistent manner without creating undue burden, alternative strategies are required. OBJECTIVES: The aim of this study is to evaluate the impact of a real-time documentation assistance tool, named AutoDx, on the volume of coding queries and encounter-level outcome metrics, including case-mix index (CMI). METHODS: The AutoDx tool was developed utilizing tools existing within the electronic health record, and is based on the generation of messages when clinical conditions are met. These messages appear within provider notes and required little to no interaction. Initial diagnoses included in the tool were electrolyte deficiencies, obesity, and malnutrition. The tool was piloted in a cohort of Hospital Medicine providers, then expanded to the Neuro Intensive Care Unit (NICU), with addition diagnoses being added. RESULTS: The initial Hospital Medicine implementation evaluation included 590 encounters pre- and 531 post-implementation. The volume of coding queries decreased 57% (p < 0.0001) for the targeted diagnoses compared with 6% (p = 0.77) in other high-volume diagnoses. In the NICU cohort, 829 encounters pre-implementation were compared with 680 post. The proportion of AutoDx coding queries compared with all other coding queries decreased from 54.9 to 37.1% (p < 0.0001). During the same period, CMI demonstrated a significant increase post-implementation (4.00 vs. 4.55, p = 0.02). CONCLUSION: The real-time documentation assistance tool led to a significant decrease in coding queries for targeted diagnoses in two unique provider cohorts. This improvement was also associated with a significant increase in CMI during the implementation time period.

Peptidoglycan endopeptidase MepM of uropathogenic Escherichia coli contributes to competitive fitness during urinary tract infections.

BACKGROUND: Urinary tract infections (UTIs) are common bacterial infections, primarily caused by uropathogenic Escherichia coli (UPEC), leading to significant health issues and economic burden. Although antibiotics have been effective in treating UPEC infections, the rise of antibiotic-resistant strains hinders their efficacy. Hence, identifying novel bacterial targets for new antimicrobial approaches is crucial. Bacterial factors required for maintaining the full virulence of UPEC are the potential target. MepM, an endopeptidase in E. coli, is involved in the biogenesis of peptidoglycan, a major structure of bacterial envelope. Given that the bacterial envelope confronts the hostile host environment during infections, MepM's function could be crucial for UPEC's virulence. This study aims to explore the role of MepM in UPEC pathogenesis. RESULTS: MepM deficiency significantly impacted UPEC's survival in urine and within macrophages. Moreover, the deficiency hindered the bacillary-to-filamentous shape switch which is known for aiding UPEC in evading phagocytosis during infections. Additionally, UPEC motility was downregulated due to MepM deficiency. As a result, the mepM mutant displayed notably reduced fitness in causing UTIs in the mouse model compared to wild-type UPEC. CONCLUSIONS: This study provides the first evidence of the vital role of peptidoglycan endopeptidase MepM in UPEC's full virulence for causing UTIs. MepM's contribution to UPEC pathogenesis may stem from its critical role in maintaining the ability to resist urine- and immune cell-mediated killing, facilitating the morphological switch, and sustaining motility. Thus, MepM is a promising candidate target for novel antimicrobial strategies.

Effects of self-efficacy on frontal midline theta power and golf putting performance.

Introduction: Self-efficacy (SE), defined as an individual's belief in their ability to complete a task, is linked to top-down attentional control, influencing motor performance in sports. Although the behavioral effects of SE are well-documented, there is a lack of research on the mechanisms through which SE affects sports performance. Our research aims to elucidate the neurophysiological mechanisms that underlie the impact of self-efficacy on sports performance. Specifically, we intend to explore the effects of low and high SE on frontal midline theta (Fmθ) activity, associated with sustained top-down attention, and on motor performance. Methods: We recruited thirty-four professional golfers to perform 60 putts, during which their electroencephalographic activity was monitored. SE levels were assessed using a visual analog scale from 0 to 10 before each putt, with scores categorized into higher or lower SE based on each golfer's individual average score. Results: Paired t-tests indicated that trials with higher SE scores had a higher putting success rate than those with lower SE scores (53.3% vs. 46.7%). Furthermore, trials associated with higher SE scores exhibited lower Fmθ activity compared to those with lower SE scores (4.49 vs. 5.18). Discussion: Our results suggest that higher SE is associated with reduced top-down attentional control, leading to improved putting performance. These findings support Bandura's theory of SE, which suggests that the effects of efficacy beliefs are mediated by cognitive, motivational, emotional, and decision-making processes. This study sheds light on the intermediate processes of SE by examining its impact on the anticipation of outcomes, sports performance, and attentional control prior to putting.

First report of the chromosomal integration of carbapenemase gene blaIMP-19 in Acinetobacter baumannii AB322: the legacy of integron in phage-plasmid?

Integration of carbapenemase gene blaIMP into the chromosome of carbapenem-resistant Acinetobacter baumannii (CRAB) has not been reported. The aim of this study was to explore the genomic characteristics of CRAB AB322 isolated from a Taiwanese patient diagnosed with bacteremia in 2011, whose chromosome harbors blaIMP-19. Disk diffusion and broth microdilution were employed to analyze the antimicrobial susceptibility of AB322 to 14 antimicrobials. Nanopore whole-genome sequencing platform was utilized for AB322 genome sequencing, and conjugation was further performed to investigate the transferability of blaIMP-19 to amikacin-resistant A. baumannii 218 (AB218) and Acinetobacter nosocomialis 254 (AN254). The results showed that AB322 was classified as multidrug-resistant A. baumannii but remained susceptible to ampicillin/sulbactam, colistin, and tigecycline. Whole-genome sequencing revealed the AB322 genome, consisting of a 4,098,985-bp chromosome, a 71,590-bp conjugative plasmid named pAB322-1, and an 8,726-bp plasmid named pAB322-2. Multilocus sequence typing analysis indicated that AB322 belonged to sequence type 1. AB322 chromosome harbored numerous acquired antimicrobial resistance genes, including aph(3')-Ia, aadA1b, aadA1, aac(6')-Ib3, aac (3)-Ia, blaADC-25, blaOXA-69, blaIMP-19, catA1, sul1, and tet(A), conferring resistance to ß-lactams, aminoglycosides, chloramphenicol, sulfamethoxazole, and tetracyclines. Moreover, blaIMP-19 was identified to be situated within class 1 integron In240 and an incomplete PHAGE_Salmon_SJ46_NC_031129 on AB322 chromosome. However, conjugation experiments revealed that blaIMP-19 could not be transferred to AB218 and AN254 in our testing conditions. In conclusion, we first report the presence of chromosomal-integrated blaIMP-19 in CRAB, possibly mediated by integron. The future dissemination of blaIMP-19 among different species, leading to carbapenem resistance dissemination, requires close monitoring. IMPORTANCE: The horizontal transfer of antimicrobial-resistant genes is crucial for the dissemination of resistance, especially as Acinetobacter baumannii has emerged as a clinically significant pathogen. However, in this study, we first report the integration of the blaIMP-19 gene into the chromosome of A. baumannii, and such horizontal transfer may be associated with integron-phage elements. Additionally, it is possible that these DNA fragments carrying antimicrobial-resistant genes could further spread to other pathogens by moving horizontally onto conjugative plasmids.

Intestinal dual-specificity phosphatase 6 regulates the cold-induced gut microbiota remodeling to promote white adipose browning.

Gut microbiota rearrangement induced by cold temperature is crucial for browning in murine white adipose tissue. This study provides evidence that DUSP6, a host factor, plays a critical role in regulating cold-induced gut microbiota rearrangement. When exposed to cold, the downregulation of intestinal DUSP6 increased the capacity of gut microbiota to produce ursodeoxycholic acid (UDCA). The DUSP6-UDCA axis is essential for driving Lachnospiraceae expansion in the cold microbiota. In mice experiencing cold-room temperature (CR) transitions, prolonged DUSP6 inhibition via the DUSP6 inhibitor (E/Z)-BCI maintained increased cecal UDCA levels and cold-like microbiota networks. By analyzing DUSP6-regulated microbiota dynamics in cold-exposed mice, we identified Marvinbryantia as a genus whose abundance increased in response to cold exposure. When inoculated with human-origin Marvinbryantia formatexigens, germ-free recipient mice exhibited significantly enhanced browning phenotypes in white adipose tissue. Moreover, M. formatexigens secreted the methylated amino acid Nε-methyl-L-lysine, an enriched cecal metabolite in Dusp6 knockout mice that reduces adiposity and ameliorates nonalcoholic steatohepatitis in mice. Our work revealed that host-microbiota coadaptation to cold environments is essential for regulating the browning-promoting gut microbiome.

Characterization of the broad-spectrum antibacterial activity of bacteriocin-like inhibitory substance-producing probiotics isolated from fermented foods.

Antimicrobial peptides, such as bacteriocin, produced by probiotics have become a promising novel class of therapeutic agents for treating infectious diseases. Selected lactic acid bacteria (LAB) isolated from fermented foods with probiotic potential were evaluated for various tests, including exopolysaccharide production, antibiotic susceptibility, acid and bile tolerance, antibacterial activity, and cell adhesion and cytotoxicity to gastric cell lines. Six selected LAB strains maintained their high viability under gastrointestinal conditions, produced high exopolysaccharides, showed no or less cytotoxicity, and adhered successfully to gastric cells. Furthermore, three strains, Weissella confusa CYLB30, Lactiplantibacillus plantarum CYLB47, and Limosilactobacillus fermentum CYLB55, demonstrated a strong antibacterial effect against drug-resistant Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella enterica serovar Choleraesuis, Enterococcus faecium, and Staphylococcus aureus. Whole genome sequencing was performed on these three strains using the Nanopore platform; then, the results showed that all three strains did not harbor genes related to toxins, superantigens, and acquired antimicrobial resistance, in their genome. The bacteriocin gene cluster was found in CYLB47 genome, but not in CYLB30 and CYLB55 genomes. In SDS-PAGE, the extract of CYLB30 and CYLB47 bacteriocin-like inhibitory substance (BLIS) yielded a single band with a size of less than 10 kDa. These BLIS inhibited the growth and biofilm formation of drug-resistant P. aeruginosa and methicillin-resistant S. aureus (MRSA), causing membrane disruption and inhibiting adhesion ability to human skin HaCaT cells. Moreover, CYLB30 and CYLB47 BLIS rescued the larvae after being infected with P. aeruginosa and MRSA infections. In conclusion, CYLB30 and CYLB47 BLIS may be potential alternative treatment for multidrug-resistant bacteria infections.

A 19-year longitudinal study to characterize carbapenem-nonsusceptible Acinetobacter isolated from patients with bloodstream infections and the contribution of conjugative plasmids to carbapenem resistance and virulence.

BACKGROUND: This study aimed to characterize carbapenem-nonsusceptible Acinetobacter (CNSA) isolated from patients with bacteremia from 1997 to 2015. METHODS: A total of 173 CNSA (12.3%) was recovered from 1403 Acinetobacter isolates. The presence of selected ß-lactamase genes in CNSA was determined by PCR amplification. The conjugation test was used to determine the transferability of metallo-ß-lactamase (MBL)-carrying plasmids. Whole genome sequencing in combination with phenotypic assays was carried out to characterize MBL-plasmids. RESULTS: In general, a trend of increasing numbers of CNSA was observed. Among the 173 CNSA, A. baumannii (54.9%) was the most common species, followed by A. nosocomialis (23.1%) and A. soli (12.1%). A total of 49 (28.3%) CNSA were extensively drug-resistant, and all were A. baumannii. The most common class D carbapenemase gene in 173 CNSA was blaOXA-24-like (32.4%), followed by ISAba1-blaOXA-51-like (20.8%), ISAba1-blaOXA-23 (20.2%), and IS1006/IS1008-blaOXA-58 (11.6%). MBL genes, blaVIM-11,blaIMP-1, and blaIMP-19 were detected in 9 (5.2%), 20 (11.6%), and 1 (0.6%) CNSA isolates, respectively. Transfer of MBL genes to AB218 and AN254 recipient cells was successful for 7 and 6 of the 30 MBL-plasmids, respectively. The seven AB218-derived transconjugants carrying MBL-plasmids produced less biofilm but showed higher virulence to larvae than recipient AB218. CONCLUSIONS: Our 19-year longitudinal study revealed a stable increase in CNSA during 2005-2015. blaOXA-24-like, ISAba1-blaOXA-51-like, and ISAba1-blaOXA-23 were the major determinants of Acinetobacter carbapenem resistance. MBL-carrying plasmids contribute not only to the carbapenem resistance but also to A. baumannii virulence.

Molecular characterization of lugdunin inactivation mechanisms and their association with Staphylococcus lugdunensis genetic types.

BACKGROUND AND PURPOSE: Our previous studies showed that lugdunin activities are associated with Staphylococcus lugdunensis genotypes, and most isolates do not exhibit lugdunin activity. As a continuation of our previous analysis, we focused on the reasons for defects in lugdunin production in S. lugdunensis clinical isolates. METHODS: A comparative analysis of 36 S. lugdunensis whole genome sequencing data revealed three major mutation types, unknown deletion mechanism that caused most of lug operon genes lost, mobile genetic element (MGE) insertion, and nonsense mutations, which potentially damaged lugdunin production. A total of 152 S. lugdunensis clinical isolates belonging to lugdunin nonproducers were further examined for the above three mutation types. PCR products were sequenced to examine these variations. RESULTS: Forty-six of the 152 isolates were CRISPR-Cas IIC isolates, including 26 ST27, 14 ST4, and 6 ST29 isolates; further investigation confirmed that all of their lug operons had lost almost all lug operon genes except lugM. An IS256 insertion in lugA was identified in 16 isolates, and most isolates (15 over 16) belonged to ST3. In addition, three nonsense mutations caused by single nucleotide substitutions (an adenine deletion in lugB at the 361th and 1219th nucleotides and an adenine deletion in lugC at the 1612nd nucleotide) that were frequently observed among 36 S. lugdunensis whole genome sequencing data were further observed in our clinical isolates. These three nonsense mutations were frequently found in most of CRISPR-Cas IIIA strains, especially in ST6 isolates. CONCLUSION: Our findings suggest that the mechanisms affecting lugdunin production are associated with S. lugdunensis molecular types.

Platinum-Ruthenium Dual-Atomic Sites Dispersed in Nanoporous Ni0.85Se Enabling Ampere-Level Current Density Hydrogen Production.

Alkaline anion-exchange-membrane water electrolyzers (AEMWEs) using earth-abundant catalysts is a promising approach for the generation of green H2. However, the AEMWEs with alkaline electrolytes suffer from poor performance at high current density compared to proton exchange membrane electrolyzers. Here, atomically dispersed Pt-Ru dual sites co-embedded in nanoporous nickel selenides (np/Pt1Ru1-Ni0.85Se) are developed by a rapid melt-quenching approach to achieve highly-efficient alkaline hydrogen evolution reaction. The np/Pt1Ru1-Ni0.85Se catalyst shows ampere-level current density with a low overpotential (46 mV at 10 mA cm-2 and 225 mV at 1000 mA cm-2), low Tafel slope (32.4 mV dec-1), and excellent long-term durability, significantly outperforming the benchmark Pt/C catalyst and other advanced large-current catalysts. The remarkable HER performance of nanoporous Pt1Ru1-Ni0.85Se is attributed to the strong intracrystal electronic metal-support interaction (IEMSI) between Pt-Se-Ru sites and Ni0.85Se support which can greatly enlarge the charge redistribution density, reduce the energy barrier of water dissociation, and optimize the potential determining step. Furthermore, the assembled alkaline AEMWE with an ultralow Pt and Ru loading realizes an industrial-level current density of 1 A cm-2 at 1.84 volts with high durability.

A longitudinal epidemiology study of fluoroquinolone-nonsusceptible Klebsiella pneumoniae reveals an increasing prevalence of qnrB and qnrS in Taiwan.

BACKGROUND: Our objective was to investigate the prevalence of plasmid-mediated quinolone resistance (PMQR) genes in fluoroquinolone-nonsusceptible Klebsiella pneumoniae (FQNSKP) in Taiwan, 1999-2022. METHODS: A total of 938 FQNSKP isolates were identified from 1966 isolates. The presence of PMQR and virulence genes, antimicrobial susceptibility, capsular types, and PMQR-plasmid transferability were determined. RESULTS: An increasing number of PMQR-containing FQNSKP isolates were observed over the study period. Our results showed that 69.0% (647 isolates) of FQNSKP isolates contained at least one PMQR gene, and 40.6%, 37.0%, and 33.9% of FQNSKP carried aac(6')-Ib-cr, qnrB, and qnrS, respectively. None of FQNSKP carried qepA and qnrC. The most common combination of PMQR genes was aac(6')-Ib-cr and qnrB (12.3%). The presence of PMQR genes is strongly related to resistance to aminoglycoside, cephalosporin, tetracycline, and sulfamethoxazole/trimethoprim in FQNSKP. The capsular serotype K64 is the most common serotype we tested in both the non-PMQR and PMQR FQNSKP isolates, while K20 showed a higher prevalence in PMQR isolates. The magA and peg-344 genes showed a significantly higher prevalence rate in non-PMQR isolates than in PMQR isolates. Eleven isolates that carried the PMQR and carbapenemase genes were identified; however, three successful transconjugants showed that the PMQR and carbapenemase genes were not located on the same plasmid. CONCLUSIONS: Our results indicated an increasing prevalence of PMQR genes, especially qnrB and qnrS, in FQNSKP in Taiwan. Moreover, the distribution of PMQR genes was associated with capsular serotypes and antimicrobial resistance gene and virulence gene distribution in FQNSKP.

Isolation and characterizations of multidrug-resistant human cancer cells by a biodegradable nano-sensor.

Multidrug resistance (MDR) remains a significant challenge in cancer therapy, with inherent and acquired resistance distinct. While conventional drug selection processes enable the isolation of cancer cells with acquired multidrug resistance, identifying cancer cells with inherent drug resistance remains challenging. Herein, we proposed a molecular beacon (MB)-based strategy to identify and isolate the inherent MDR cancer cells. A lipid/PLGA core-shell nanoparticulate system (DNCP) was designed to deliver MB for intracellular MDR1 mRNA imaging. DNCP-MB - possess a surface potential of -8 mV and a size of 150 nm - demonstrated effective delivery of MB, remarkable selectivity towards the selected intracellular mRNA targets, and low cytotoxicity. Following DNCP transfection, fluorescence-activated cell sorting (FACS) was employed to differentiate MCF-7 cells into two distinct sub-populations: the Top 10 cells with a high level of MDR gene expression and the Bottom 10 cells with a low level of MDR gene expression, which represent inherent drug-resistant and non-drug-resistant cells, respectively. Intriguingly, we observed a positive correlation between elevated MDR1 mRNA expression and increased migration, enhanced proliferation rate, and tighter spheroid formation. Moreover, we conducted RNA sequencing analysis on the Top 10, Bottom 10, and MCF-7/ADR cells. The findings revealed a notable disparity in the gene ontology enrichment analysis of differentially expressed genes between the Top 10 and Bottom 10 cells when compared to the Bottom 10 and MCF-7/ADR cells. This novel approach provides a promising avenue for isolating inherent drug-resistant cells and holds significant potential in unraveling the mechanisms underlying inherent drug resistance.

Constructing Nanoporous Ir/Ta2 O5 Interfaces on Metallic Glass for Durable Acidic Water Oxidation.

Although proton exchange membrane water electrolyzers (PEMWE) are considered as a promising technique for green hydrogen production, it remains crucial to develop intrinsically effective oxygen evolution reaction (OER) electrocatalysts with high activity and durability. Here, a flexible self-supporting electrode with nanoporous Ir/Ta2O5 electroactive surface is reported for acidic OER via dealloying IrTaCoB metallic glass ribbons. The catalyst exhibits excellent electrocatalytic OER performance with an overpotential of 218 mV for a current density of 10 mA cm-2 and a small Tafel slope of 46.1 mV dec-1 in acidic media, superior to most electrocatalysts. More impressively, the assembled PEMWE with nanoporous Ir/Ta2 O5 as an anode shows exceptional performance of electrocatalytic hydrogen production and can operate steadily for 260 h at 100 mA cm-2 . In situ spectroscopy characterizations and density functional theory calculations reveal that the modest adsorption of OOH* intermediates to active Ir sites lower the OER energy barrier, while the electron donation behavior of Ta2 O5 to stabilize the high-valence states of Ir during the OER process extended catalyst's durability.

Radiomics analysis for the prediction of locoregional recurrence of locally advanced oropharyngeal cancer and hypopharyngeal cancer.

PURPOSE: By radiomic analysis of the postcontrast CT images, this study aimed to predict locoregional recurrence (LR) of locally advanced oropharyngeal cancer (OPC) and hypopharyngeal cancer (HPC). METHODS: A total of 192 patients with stage III-IV OPC or HPC from two independent cohort were randomly split into a training cohort with 153 cases and a testing cohort with 39 cases. Only primary tumor mass was manually segmented. Radiomic features were extracted using PyRadiomics, and then the support vector machine was used to build the radiomic model with fivefold cross-validation process in the training data set. For each case, a radiomics score was generated to indicate the probability of LR. RESULTS: There were 94 patients with LR assigned in the progression group and 98 patients without LR assigned in the stable group. There was no significant difference of TNM staging, treatment strategies and common risk factors between these two groups. For the training data set, the radiomics model to predict LR showed 83.7% accuracy and 0.832 (95% CI 0.72, 0.87) area under the ROC curve (AUC). For the test data set, the accuracy and AUC slightly declined to 79.5% and 0.770 (95% CI 0.64, 0.80), respectively. The sensitivity/specificity of training and test data set for LR prediction were 77.6%/89.6%, and 66.7%/90.5%, respectively. CONCLUSIONS: The image-based radiomic approach could provide a reliable LR prediction model in locally advanced OPC and HPC. Early identification of those prone to post-treatment recurrence would be helpful for appropriate adjustments to treatment strategies and post-treatment surveillance.

Epigenetic regulator RNF20 underlies temporal hierarchy of gene expression to regulate postnatal cardiomyocyte polarization.

Differentiated cardiomyocytes (CMs) must undergo diverse morphological and functional changes during postnatal development. However, the mechanisms underlying initiation and coordination of these changes remain unclear. Here, we delineate an integrated, time-ordered transcriptional network that begins with expression of genes for cell-cell connections and leads to a sequence of structural, cell-cycle, functional, and metabolic transitions in mouse postnatal hearts. Depletion of histone H2B ubiquitin ligase RNF20 disrupts this gene network and impairs CM polarization. Subsequently, assay for transposase-accessible chromatin using sequencing (ATAC-seq) analysis confirmed that RNF20 contributes to chromatin accessibility in this context. As such, RNF20 is likely to facilitate binding of transcription factors at the promoters of genes involved in cell-cell connections and actin organization, which are crucial for CM polarization and functional integration. These results suggest that CM polarization is one of the earliest events during postnatal heart development and provide insights into how RNF20 regulates CM polarity and the postnatal gene program.

Cell-based screen identifies porphyrins as FGFR3 activity inhibitors with therapeutic potential for achondroplasia and cancer.

Overactive fibroblast growth factor receptor 3 (FGFR3) signaling drives pathogenesis in a variety of cancers and a spectrum of short-limbed bone dysplasias, including the most common form of human dwarfism, achondroplasia (ACH). Targeting FGFR3 activity holds great promise as a therapeutic approach for treatment of these diseases. Here, we established a receptor/adaptor translocation assay system that can specifically monitor FGFR3 activation, and we applied it to identify FGFR3 modulators from complex natural mixtures. An FGFR3-suppressing plant extract of Amaranthus viridis was identified from the screen, and 2 bioactive porphyrins, pheophorbide a (Pa) and pyropheophorbide a, were sequentially isolated from the extract and functionally characterized. Further analysis showed that Pa reduced excessive FGFR3 signaling by decreasing its half-life in FGFR3-overactivated multiple myeloma cells and chondrocytes. In an ex vivo culture system, Pa alleviated defective long bone growth in humanized ACH mice (FGFR3ACH mice). Overall, our study presents an approach to discovery and validation of plant extracts or drug candidates that target FGFR3 activation. The compounds identified by this approach may have applications as therapeutics for FGFR3-associated cancers and skeletal dysplasias.