Unveiling the imprinted dance: how parental genomes orchestrate seed development and hybrid success.

Parental epigenetic asymmetries, which contribute to the monoallelic expression of genes known as imprints, play a critical role in seed development in flowering plants. Primarily, differential DNA methylation patterns and histone modifications on parental alleles form the molecular basis of gene imprinting. Plants predominantly exhibit this non-Mendelian inheritance phenomenon in the endosperm and the early embryo of developing seeds. Imprinting is crucial for regulating nutrient allocation, maintaining seed development, resolving parental conflict, and facilitating evolutionary adaptation. Disruptions in imprinted gene expression, mediated by epigenetic regulators and parental ploidy levels, can lead to endosperm-based hybridization barriers and hybrid dysfunction, ultimately reducing genetic diversity in plant populations. Conversely, imprinting helps maintain genetic stability within plant populations. Imprinted genes likely influence seed development in various ways, including ensuring proper endosperm development, influencing seed dormancy, and regulating seed size. However, the functions of most imprinted genes, the evolutionary significance of imprinting, and the long-term consequences of imprinting disruptions on plant development and adaptation need further exploration. Thus, it is clear that research on imprinting has immense potential for improving our understanding of plant development and ultimately enhancing key agronomic traits. This review decodes the possible genetic and epigenetic regulatory factors underpinning genomic imprinting and their positive and negative consequences on seed development. This study also forecasts the potential implications of exploiting gene imprinting for crop improvement programs.

Long-term efficacy of drug-coated balloon-based treatment for de novo left anterior descending artery disease.

Drug-coated balloons (DCB) are increasingly utilized in percutaneous coronary intervention (PCI), but their effectiveness in coronary artery disease (CAD) needs further exploration. This study investigates the efficacy and safety of a DCB-based strategy for de novo left anterior descending artery (LAD) disease. Patients with de novo LAD lesions treated with DCB alone or combined with drug-eluting stents (DES) and were retrospectively enrolled from 2010 to 2023 (n = 268). The comparator group consisted of patients treated with second-generation DES from a Korean multicenter registry (n = 4,147). The primary endpoint was three-year major adverse cardiovascular events (MACE), including cardiac death, myocardial infarction, target vessel revascularization, target lesion thrombosis, and major bleeding. In the DCB-based group (n = 268), 218 (81.3%) received DCB-only, while 50 (18.7%) underwent a hybrid approach. After propensity score-matching of 243 paired subjects, baseline characteristics were balanced. The DCB-based PCI reduced overall stent burden by 86.7% and significantly lowered the risk of MACE at three years compared to DES-only PCI (4.5% vs. 7.6%, HR 0.50, 95% CI 0.28-0.90; p = 0.020). The most significant reduction was in major bleeding. The DCB-based approach offers an alternative to DES-only strategy for LAD PCI by reducing three-year MACE risk, supporting its use in treating de novo CAD.

Ninjurin1 deficiency differentially mitigates colorectal cancer induced by azoxymethane and dextran sulfate sodium in male and female mice.

This study investigated the role of Ninjurin1 (Ninj1), encoding a small transmembrane protein, in colitis-associated colon tumorigenesis in relation to sex hormones. Male and female wild-type (WT) and Ninj1 knockout (KO) mice were treated with azoxymethane (AOM) and dextran sulfate sodium (DSS), with or without testosterone propionate (TP). At week 2 (acute colitis stage), Ninj1 KO exhibited an alleviation in the colitis symptoms in both male and female mice. The M2 macrophage population increased and CD8+ T cell population decreased only in the female Ninj1 KO than in the female WT AOM/DSS group. In the female AOM/DSS group, TP treatment exacerbated colon shortening in the Ninj1 KO than in the WT. At week 13 (tumorigenesis stage), male Ninj1 KO mice had fewer tumors, but females showed similar tumors. In the WT AOM/DSS group, females had more M2 macrophages and fewer M1 macrophages than males, but this difference was absent in Ninj1 KO mice. In the Ninj1 KO versus WT group, the expression of pro-inflammatory mediators and Ho-1 and CD8+ T cell populations decreased in both female and male Ninj1 KO mice. In the WT group, M2 macrophage populations were increased by AOM/DSS treatment and decreased by TP treatment. However, neither treatment changed the cell populations in the Ninj1 KO group. These results suggest that Ninj1 is involved in colorectal cancer development in a testosterone-dependent manner, which was different in male and female. This highlights the importance of considering sex disparities in understanding Ninj1's role in cancer pathogenesis.

Diagnostic performance of angiography-derived fractional flow reserve compared to pressure wire-derived fractional flow reserve: Rationale and design of MPFFR pivotal trial.

BACKGROUND: Cardiovascular disease remains the leading cause of death and the use of percutaneous coronary intervention (PCI) is steadily increasing. Current guidelines advocate the use of the fractional flow reserve (FFR) to assess coronary stenosis and treatment strategies; however, invasive FFR has some limitations. Angiography-derived FFR is a potential alternative for calculating FFR from two-dimensional (2D) angiographic images, thereby reducing invasiveness and complications. A novel artificial intelligence (AI)-based angiography-derived FFR, named "MPFFR," offers automated operator-independent hemodynamic calculations; this phase 3 trial aims to validate its diagnostic performance against 2D-quantitative coronary angiography (QCA). METHODS AND ANALYSIS: This pivotal MPFFR trial is a prospective, multicenter, single-blind study. This trial involves patients with coronary artery disease (CAD) from eight cardiovascular centers. Invasive FFR will be performed according to standard guidelines and defined as the reference standard. Angiography-derived FFR will be computed using a proprietary method and 2D-QCA will be performed using validated software. The primary endpoint is the area under the curve for identifying physiologically significant coronary stenosis (FFR ≤0.80), with secondary endpoints including diagnostic accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and correlations between angiography-derived and invasive FFR. This study is designed to demonstrate the superiority of angiography-derived FFR over 2D-QCA and is powered to achieve this with a sample size of 240 patients. Medipixel Inc. supports the trial and is not involved in the data analysis or management.

Deep learning-based analysis of EGFR mutation prevalence in lung adenocarcinoma H&E whole slide images.

EGFR mutations are a major prognostic factor in lung adenocarcinoma. However, current detection methods require sufficient samples and are costly. Deep learning is promising for mutation prediction in histopathological image analysis but has limitations in that it does not sufficiently reflect tumor heterogeneity and lacks interpretability. In this study, we developed a deep learning model to predict the presence of EGFR mutations by analyzing histopathological patterns in whole slide images (WSIs). We also introduced the EGFR mutation prevalence (EMP) score, which quantifies EGFR prevalence in WSIs based on patch-level predictions, and evaluated its interpretability and utility. Our model estimates the probability of EGFR prevalence in each patch by partitioning the WSI based on multiple-instance learning and predicts the presence of EGFR mutations at the slide level. We utilized a patch-masking scheduler training strategy to enable the model to learn various histopathological patterns of EGFR. This study included 868 WSI samples from lung adenocarcinoma patients collected from three medical institutions: Hallym University Medical Center, Inha University Hospital, and Chungnam National University Hospital. For the test dataset, 197 WSIs were collected from Ajou University Medical Center to evaluate the presence of EGFR mutations. Our model demonstrated prediction performance with an area under the receiver operating characteristic curve of 0.7680 (0.7607-0.7720) and an area under the precision-recall curve of 0.8391 (0.8326-0.8430). The EMP score showed Spearman correlation coefficients of 0.4705 (p = 0.0087) for p.L858R and 0.5918 (p = 0.0037) for exon 19 deletions in 64 samples subjected to next-generation sequencing analysis. Additionally, high EMP scores were associated with papillary and acinar patterns (p = 0.0038 and p = 0.0255, respectively), whereas low EMP scores were associated with solid patterns (p = 0.0001). These results validate the reliability of our model and suggest that it can provide crucial information for rapid screening and treatment plans.

Arenicolide Family Macrolides Provide a New Therapeutic Lead Combating Multidrug-resistant Tuberculosis.

The emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis (Mtb) poses a significant threat to health globally. During searching for new chemical entities regulating MDR- and XDR-Mtb, chemical investigation of the black oil beetle gut bacterium Micromonospora sp. GR10 led to the discovery of eight new members of arenicolides along with the identification of arenicolide A (Ar-A, 1), which was a previously reported macrolide with incomplete configuration. Genomic analysis of the bacterial strain GR10 revealed their putative biosynthetic pathway. Quantum mechanics-based computation, chemical derivatizations, and bioinformatic analysis established the absolute stereochemistry of Ar-A and arenicolides D-K (Ar-D-K, 2-9) completely for the first time. Biological studies of 1-9 revealed their antimicrobial activity against MDR and XDR strains of Mtb. Ar-A had the most potent in vitro antimicrobial efficacy against MDR- and XDR-Mtb. Mechanistically, Ar-A induced ATP depletion and destabilized Mtb cell wall, thereby inhibiting growth. Notably, Ar-A exerted a significant antimicrobial effect against Mtb in macrophages, was effective in the treatment of Mtb infections, and showed a synergistic effect with amikacin (AMK) in a mouse model of MDR-Mtb lung infection. Collectively, our findings indicate Ar-A to be a promising drug lead for drug-resistant tuberculosis.

Association between hepatocyte TM4SF5 expression and gut microbiome dysbiosis during non-alcoholic fatty liver disease development.

Gut microbiome dysbiosis is involved in non-alcoholic fatty liver disease (NAFLD) development. Hepatic transmembrane 4 L six family member 5 (TM4SF5) overexpression promotes NAFLD. However, how gut microbiota are associated with TM4SF5-mediated NAFLD remains unexplored. We analyzed the gut microbiome using feces from hepatocyte-specific TM4SF5-overexpressing transgenic (Alb-TGTm4sf5-Flag, TG) or Tm4sf5-/- knock-out (KO) mice fed a normal chow diet (NCD), high-fat diet (HFD) for 2 weeks (HFD2W), or methionine-choline-deficient diet (MCD) for 4 weeks to investigate associations among Tm4sf5 expression, diet, and the gut microbiome. TG-NCD mice showed a higher Firmicutes-to-Bacteroidetes (F/B) ratio, with less enrichment of Akkermansia muciniphila and Lactobacillus reuteri. NASH-related microbiomes in feces were more abundant in TG-HFD2w mice than in KO-HFD2w mice. Further, TG-MCD showed a higher F/B ratio than TG-NCD or KO mice, with decreases or increases in microbiomes beneficial or detrimental to the liver, respectively. Such effects in TG-MCD animals were correlated with functional pathways producing short-chain fatty acids (SCFAs). Furthermore, potential functional pathways of the gut microbiome were metabolically parallel to NAFLD features in TG-MCD mice. These results suggest that hepatocyte Tm4sf5 supports gut microbiome dysbiosis and metabolic activity, leading to SCFA production and hepatic inflammation during NAFLD development.

Introgression of Herbicide-Resistant Gene from Genetically Modified Brassica napus L. to Brassica rapa through Backcrossing.

Interspecific hybridization between two different Brassicaceae species, namely Brassica rapa ssp. pekinensis (♀) (AA, 2n = 2x = 20) and genetically modified Brassica napus (♂) (AACC, 2n = 4x = 38), was performed to study the transmission of a herbicide resistance gene from a tetraploid to a diploid Brassica species. Initially, four different GM B. napus lines were used for hybridization with B. rapa via hand pollination. Among the F1 hybrids, the cross involving the B. rapa (♀) × GM B. napus (♂) TG#39 line exhibited the highest recorded crossability index of 14.7 ± 5.7. However, subsequent backcross progenies (BC1, BC2, and BC3) displayed notably lower crossability indices. The F1 plants displayed morphological characteristics more aligned with the male parent B. napus, with significant segregation observed in the BC1 generation upon backcrossing with the recurrent parent B. rapa. By the BC2 and BC3 generations, the progeny stabilized, manifesting traits from both parents to varying degrees. Cytogenetic analysis revealed a substantial reduction in chromosome numbers, particularly in backcrossing progenies. BC1 plants typically exhibited 21-25 chromosomes, while BC2 progenies showed 21-22 chromosomes, and by the BC3 generation, stability was achieved with an average of 20 chromosomes. SSR marker analysis confirmed the progressive reduction of C-genome regions, retaining minimal C-genome-specific bands throughout successive backcrossing. Despite the extensive elimination of C-genome-specific genomic regions, the glyphosate resistance gene from the male parent B. napus was introgressed into BC3 progenies, suggesting that the glyphosate resistance gene located and introgressed in A-chromosome/genome regions of the Brassica plants.

Drug-Coated Balloon Angioplasty of the Side Branch During Provisional Stenting: The Multicenter Randomized DCB-BIF Trial.

BACKGROUND: Side branch stenting is often required during provisional stenting, leading to suboptimal results. Drug-coated balloons (DCB) for the compromised side branch have emerged as an attractive strategy. However, the benefit of DCB for coronary bifurcations remains unclear. OBJECTIVES: This study aimed to investigate whether DCB, compared with a noncompliant balloon (NCB), for the pinched side branch improves the outcomes of provisional stenting in patients with simple, true coronary bifurcations. METHODS: In this multicenter, randomized controlled trial, patients with true coronary bifurcations who had side branch diameter stenosis of ≥70% after main vessel stenting at 22 centers in China, Indonesia, Italy, and Korea were randomly assigned to either DCB or NCB intervention. The primary endpoint was major adverse cardiac events, a composite of cardiac death, target vessel myocardial infarction, or clinically driven target-lesion revascularization at the 1-year follow-up. RESULTS: Between September 8, 2020, and June 2, 2023, 784 patients with true coronary bifurcation lesions undergoing main vessel stenting and having a severely compromised side branch were randomly assigned to the DCB (n = 391) or NCB (n = 393) group. One-year follow-up was completed in all patients. The primary endpoint occurred in 28 patients in the DCB group and 49 patients in the NCB group (Kaplan-Meier rate: 7.2% vs 12.5%; HR: 0.56; 95% CI: 0.35-0.88; P = 0.013), driven by a reduction in myocardial infarction. There were no significant differences between groups in procedural success, crossover to a 2-stent approach, all-cause death, revascularization, or stent thrombosis. CONCLUSIONS: In patients with simple and true coronary bifurcation lesions undergoing provisional stenting, main vessel stenting with a DCB for the compromised side branch resulted in a lower 1-year rate of the composite outcome compared with an NCB intervention for the side branch. The high rates of periprocedural myocardial infarction, which occurred early and did not lead to revascularization, are of unclear clinical significance.

Sex Difference in 5-year Relative Survival Following Percutaneous Coronary Intervention.

Background: Survival rates following percutaneous coronary intervention (PCI) show variability across studies, particularly regarding sex-specific outcomes. Relative survival analysis, which considers survival patterns in sex-and age-matched general populations, could help explain this variability. Methods: In a 2011 nationwide South Korean PCI cohort study with 48,783 patients, all-cause death was assessed as the primary outcome over 5 years. Observed and relative survival rates at 5 years conditional on surviving 0 days, 30 days, 1 year, and 2 years were assessed. Sex-specific differences in clinical characteristics were adjusted using propensity score-matching. Results: In the unadjusted analyses, 15,710 females had more cardiovascular risk factors than 33,073 males. Both observed survival (HR 1.28; 95% CI [1.22-1.34]) and relative survival (HR 1.21; 95% CI [1.16-1.27]) were lower in females than males (all p<0.001). In the analyses of 14,454 matched pairs, females showed higher observed survival (HR 0.78; 95% CI [0.74-0.82]), but lower relative survival (HR 1.19; 95% CI [1.13-1.26]), compared to males (all p<0.001). This trend was particularly notable in females aged 60 years or older. These findings persisted in analyses conditional on surviving 30 days, 1 year and 2 years. Conclusion: The adjusted 5-year relative survival of older females was lower than that of age-matched males, highlighting the need for the excessive risk reduction in older females undergoing PCI.

Developing a Microsatellite Polymerase Chain Reaction System for Small Yellow Croaker (Larimichthys polyactis) and Its Application in Parentage Assignment.

(1) Background: The small yellow croaker, an economically important fish in East Asia, has been subjected to population declines due to overfishing and environmental pressures. The development of effective breeding programs is considered crucial for the species, and accurate parentage assignment is deemed essential for such programs. (2) Methods: The assembled reference genome of the small yellow croaker was utilized to select highly polymorphic microsatellite markers. A multiplex PCR system was optimized for the simultaneous amplification of these markers. The system's accuracy was validated using controlled mating pairs and subsequently applied to a group mating scenario. (3) Results: The developed multiplex PCR system demonstrated high accuracy in assigning offspring to their parents in both the controlled and group mating scenarios. (4) Conclusions: The system is presented as a valuable tool for pedigree management, selective breeding, and conservation efforts for the small yellow croaker, facilitating sustainable aquaculture practices and genetic improvement.

Clopidogrel Versus Aspirin as Chronic Maintenance Antiplatelet Monotherapy in Patients After Percutaneous Coronary Intervention With Chronic Kidney Disease: A Post Hoc Analysis of the HOST-EXAM Trial.

BACKGROUND: Clopidogrel monotherapy improved clinical outcomes compared with aspirin monotherapy during a chronic maintenance period in patients who underwent coronary stenting in the HOST-EXAM (Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis-Extended Antiplatelet Monotherapy) trial. However, it is uncertain whether the beneficial effect of clopidogrel over aspirin is different according to the renal function. METHODS AND RESULTS: We conducted a post hoc analysis of the HOST-EXAM trial. Chronic kidney disease (CKD) was defined as baseline estimated glomerular filtration rate <60 mL/min per 1.73 m2. The primary end point was a composite of all-cause death, nonfatal myocardial infarction, stroke, readmission due to acute coronary syndrome, and Bleeding Academic Research Consortium bleeding type ≥3, during the 2-year follow up. Among the 5438 patients enrolled in the HOST-EXAM trial, 4844 patients (mean age, 63.3±10.6 years; 74.9% men) with a baseline creatinine value were analyzed in this study. A total of 508 (10.5%) patients had CKD, who were at higher risk of the primary end point compared with those without CKD (hazard ratio [HR], 2.01 [95% CI, 1.51-2.67]). Clopidogrel monotherapy was associated with a lower rate of the primary end point in both patients with CKD (HR, 0.74 [95% CI, 0.44-1.25]) and patients without CKD (HR, 0.71 [95% CI, 0.56-0.91]). No significant interaction was observed between the treatment effect and CKD status (P for interaction=0.889). CONCLUSIONS: During the chronic maintenance period after coronary stenting, the risk of thrombotic and bleeding events was significantly higher in patients with CKD compared with those without CKD. There was no statistical difference in the treatment effect of clopidogrel monotherapy in those with versus without CKD.

Neurodevelopmental imprints of sociomarkers in adolescent brain connectomes.

Neural consequences of social disparities are not yet rigorously investigated. How socioeconomic conditions influence children's connectome development remains unknown. This paper endeavors to gauge how precisely the connectome structure of the brain can predict an individual's social environment, thereby inversely assessing how social influences are engraved in the neural development of the Adolescent brain. Utilizing Adolescent Brain and Cognition Development (ABCD) data (9099 children residing in the United States), we found that social conditions both at the household and neighborhood levels are significantly associated with specific neural connections. Solely with brain connectome data, we train a linear support vector machine (SVM) to predict socio-economic conditions of those adolescents. The classification performance generally improves when the thresholds of the advantageous and disadvantageous environments compartmentalize the extreme cases. Among the tested thresholds, the 20th and 80th percentile thresholds using the dual combination of household income and neighborhood education yielded the highest Area Under the Precision-Recall Curve (AUPRC) of 0.8224. We identified 8 significant connections that critically contribute to predicting social environments in the parietal lobe and frontal lobe. Insights into social factors that contribute to early brain connectome development is critical to mitigate the disadvantages of children growing up in unfavorable neighborhoods.

An inducible sphingosine kinase 1 in hepatic stellate cells potentiates liver fibrosis.

Hepatic stellate cells (HSCs) play a role in hepatic fibrosis and sphingosine kinase (SphK) is involved in biological processes. As studies on the regulatory mechanisms and functions of SphK in HSCs during liver fibrosis are currently limited, this study aimed to elucidate the regulatory mechanism and connected pathways of SphK upon HSC activation. The expression of SphK1 was higher in HSCs than in hepatocytes, and upregulated in activated primary HSCs. SphK1 was also increased in liver homogenates of carbon tetrachloride-treated or bile duct ligated mice and in transforming growth factor-ß (TGF-ß)-treated LX-2 cells. TGF-ß-mediated SphK1 induction was due to Smad3 signaling in LX-2 cells. SphK1 modulation altered the expression of liver fibrogenesis-related genes. This SphK1-mediated profibrogenic effect was dependent on SphK1/sphingosine-1-phosphate/sphingosine-1-phosphate receptor signaling through ERK. Epigallocatechin gallate blocked TGF-ß-induced SphK1 expression and hepatic fibrogenesis by attenuating Smad and MAPK activation. SphK1 induced by TGF-ß facilitates HSC activation and liver fibrogenesis, which is reversed by epigallocatechin gallate. Accordingly, SphK1 and related signal transduction may be utilized to treat liver fibrosis.

Mitochondria Activity and CXCR4 Collaboratively Promote the Differentiation of CD11c+ B Cells Induced by TLR9 in Lupus.

Lupus is characterized by the autoantibodies against nuclear Ags, underscoring the importance of identifying the B cell subsets driving autoimmunity. Our research focused on the mitochondrial activity and CXCR4 expression in CD11c+ B cells from lupus patients after ex vivo stimulation with a TLR9 agonist, CpG-oligodeoxyribonucleotide (ODN). We also evaluated the response of CD11c+ B cells in ODN-injected mice. Post-ex vivo ODN stimulation, we observed an increase in the proportion of CD11chi cells, with elevated mitochondrial activity and CXCR4 expression in CD11c+ B cells from lupus patients. In vivo experiments showed similar patterns, with TLR9 stimulation enhancing mitochondrial and CXCR4 activities in CD11chi B cells, leading to the generation of anti-dsDNA plasmablasts. The CXCR4 inhibitor AMD3100 and the mitochondrial complex I inhibitor IM156 significantly reduced the proportion of CD11c+ B cells and autoreactive plasmablasts. These results underscore the pivotal roles of mitochondria and CXCR4 in the production of autoreactive plasmablasts.

Synergistic effects of cellulose nanocrystal on the mechanical and shape memory properties of TPU composites.

Cellulose nanocrystal is a nanomaterial that has a large specific surface area, high surface energy, and high strength. As well, it is biocompatible, environmentally friendly, nontoxic, and can be extracted from biomass resources. Because of these features, cellulose nanocrystals can be used to improve the mechanical properties of polymer matrices with a shape memory effect and as a shape memory switch. In this study, a polytrimethylene ether glycol-based thermoplastic polyurethane (TPU)/cellulose nanocrystal (CNC) composite was prepared via an in-situ polymerization process to create a self-healing polymer matrix. Also, the effect of CNC doses in low concentrations (≤2 wt%) on the different properties of the resulting bio-nanocomposite was investigated. The results showed that the introduction of CNCs affects the hydrogen bonding within the polymer matrix and provides better thermal stability in the high temperature range than pure TPU. Furthermore, the samples with 0 wt%, 0.75 wt%, 1 wt%, and 2 wt% of CNC exhibited an increasing trend in tensile strength with values of 11.71 MPa, 18.95 MPa, 17.88 MPa, and 26.18 MPa, respectively, which indicates a remarkable improvement in mechanical strength. The shape memory behavior was also notably prominent in this polymer composite, where the composite containing 2 wt% of CNC showed the fastest recovery time (240 s) at 75 °C with the highest shape retention. Moreover, their flow behavior and deformation capacity were examined through rheology tests. Besides, docking simulations were conducted in silico to assess the interaction of the TPU/CNC composite with the DNA gyrase enzyme. The interaction between CNC/TPU composite and DNA gyrase was meticulously analyzed across 10 distinct conformations, yielding docking scores ranging from -6.5 Kcal/mol to -5.3 Kcal/mol. Overall, the physico-mechanical properties of the TPU/CNC composites were substantially enhanced with the incorporation of nanofillers.

Hierarchical gradients of multiple timescales in the mammalian forebrain.

Many anatomical and physiological features of cortical circuits, ranging from the biophysical properties of synapses to the connectivity patterns among different neuron types, exhibit consistent variation along the hierarchical axis from sensory to association areas. Notably, the scale of temporal correlation of neural activity at rest, known as the intrinsic timescale, increases systematically along this hierarchy in both primates and rodents, analogous to the growing scale and complexity of spatial receptive fields. However, how the timescales for task-related activity vary across brain regions and whether their hierarchical organization appears consistently across different mammalian species remain unexplored. Here, we show that both the intrinsic timescale and the timescales of task-related activity follow a similar hierarchical gradient in the cortices of monkeys, rats, and mice. We also found that these timescales covary similarly in both the cortex and basal ganglia, whereas the timescales of thalamic activity are shorter than cortical timescales and do not conform to the hierarchical order predicted by their cortical projections. These results suggest that the hierarchical gradient of cortical timescales might be a universal feature of intra-cortical circuits in the mammalian brain.

Impact of proton pump inhibitor use on clinical outcomes in East Asian patients receiving clopidogrel following drug-eluting stent implantation.

BACKGROUND: Concomitant use of clopidogrel and proton pump inhibitor (PPI) is common, but PPI may reduce the antiplatelet effects of clopidogrel in patients undergoing percutaneous coronary intervention (PCI). We evaluated the impact of PPI use on clinical outcomes in post-PCI patients, by incorporating P2Y12 reaction unit (PRU) and CYP2C19 genotyping results. METHODS: From a multicenter registry of patients who underwent PCI with drug-eluting stent implantation and received clopidogrel-based dual antiplatelet therapy (DAPT), patients who were prescribed a PPI at the time of PCI (PPI users) were compared to those who were not (non-users). The primary outcome included all-cause death, myocardial infarction, stent thrombosis, or cerebrovascular accident at 12 months. Major bleeding (Bleeding Academic Research Consortium [BARC] types 3-5) and gastrointestinal (GI) bleeding (BARC types 3-5) were important secondary outcomes. The adjusted outcomes were compared using a 1:1 propensity-score (PS) matching and competing risk analysis. RESULTS: Of 13,160 patients, 2,235 (17.0%) were prescribed PPI, with an average age of 65.4 years. PPI users had higher on-treatment PRU levels than non-users. After PS matching, the primary outcome occurred in 51 patients who were PPI users (cumulative incidence, 4.7%) and 41 patients who were non-users (cumulative incidence, 3.7%; log-rank p = 0.27). In carriers of both CYP2C19 loss-of-function alleles, PPI use was linked to an increased risk of the primary outcome (hazard ratio, 3.22; 95% confidence interval, 1.18-8.78). The incidence of major bleeding and GI bleeding (BARC types 3-5) was comparable between PPI users and non-users in the PS-matched cohort. CONCLUSIONS: In post-PCI patients receiving clopidogrel-based DAPT, PPI use was not linked to an increased risk of adverse cardiac and cerebrovascular events, but there was a small but significant increase in on-treatment PRU. Future research using a more individualized approach would further elucidate these interactions and guide evidence-based clinical practices.

Inorganic-Derived 0D Perovskite Induced Surface Lattice Arrangement for Efficient and Stable All-Inorganic Perovskite Solar Cells.

The inverted inorganic CsPbI3 perovskite solar cells (PSCs) are prospective candidates for next-generation photovoltaics owing to inherent robust thermal/photo-stability and compatibility for tandems. However, the performance and stability of the inverted CsPbI3 PSCs fall behind the n-i-p counterparts due to poor energetic alignment and abundant interfacial defect states. Here, an inorganic 0D Cs4PbBr6 with a good lattice strain arrangement is implemented as the surface anchoring capping layer on CsPbI3. The Cs4PbBr6 perovskite induces enhanced electron-selective junction and thus facilitates efficient charge extraction and effectively inhibits non-radiative recombination. Consequently, the CsPbI3 PSCs with Cs4PbBr6 demonstrate the highest power conversion efficiency (PCE) of CsPbI3-based inverted PSCs, reaching 21.03% PCE from a unit cell and 17.39% PCE from a module with a 64 cm2 aperture area. Furthermore, the resulting devices retain 92.48% after 1000 h under simultaneous 1-sun and damp heat (85 °C / 85% relative humidity) environment.