Uncovering ghost introgression through genomic analysis of a distinct eastern Asian hickory species.

Ghost introgression, or the transfer of genetic material from extinct or unsampled lineages to sampled species, has attracted much attention. However, conclusive evidence for ghost introgression, especially in plant species, remains scarce. Here, we newly assembled chromosome-level genomes for both Carya sinensis and Carya cathayensis, and additionally re-sequenced the whole genomes of 43 C. sinensis individuals as well as 11 individuals representing 11 diploid hickory species. These genomic datasets were used to investigate the reticulation and bifurcation patterns within the genus Carya (Juglandaceae), with a particular focus on the beaked hickory C. sinensis. By combining the D-statistic and BPP methods, we obtained compelling evidence that supports the occurrence of ghost introgression in C. sinensis from an extinct ancestral hickory lineage. This conclusion was reinforced through the phylogenetic network analysis and a genome scan method VolcanoFinder, the latter of which can detect signatures of adaptive introgression from unknown donors. Our results not only dispel certain misconceptions about the phylogenetic history of C. sinensis but also further refine our understanding of Carya's biogeography via divergence estimates. Moreover, the successful integration of the D-statistic and BPP methods demonstrates their efficacy in facilitating a more precise identification of introgression types.

Development and validation of a prognostic score to identify the optimal candidate for preemptive TIPS in patients with cirrhosis and acute variceal bleeding.

BACKGROUND AND AIM: Baveno VII workshop recommends the use of preemptive TIPS (p-TIPS) in patients with cirrhosis and acute variceal bleeding (AVB) at high- risk of treatment failure. However, the criteria defining "high-risk" have low clinical accessibility or include subjective variables. We aimed to develop and externally validate a model for better identification of p-TIPS candidates. APPROACH AND RESULTS: The derivation cohort included 1554 patients with cirrhosis and AVB who were treated with endoscopy plus drug (n = 1264) or p-TIPS (n = 290) from 12 hospitals in China between 2010 and 2017. We first used competing risk regression to develop a score for predicting 6-week and 1-year mortality in patients treated with endoscopy plus drugs, which included age, albumin, bilirubin, international normalized ratio, white blood cell, creatinine, and sodium. The score was internally validated with the bootstrap method, which showed good discrimination (6 wk/1 y concordance-index: 0.766/0.740) and calibration, and outperformed other currently available models. In the second stage, the developed score was combined with treatment and their interaction term to predicate the treatment effect of p-TIPS (mortality risk difference between treatment groups) in the whole derivation cohort. The estimated treatment effect of p-TIPS varied substantially among patients. The prediction model had good discriminative ability (6 wk/1 y c -for-benefit: 0.696/0.665) and was well calibrated. These results were confirmed in the validation dataset of 445 patients with cirrhosis with AVB from 6 hospitals in China between 2017 and 2019 (6-wk/1-y c-for-benefit: 0.675/0.672). CONCLUSIONS: We developed and validated a clinical prediction model that can help to identify individuals who will benefit from p-TIPS, which may guide clinical decision-making.

High-Entropy Strategy to Achieve Electronic Band Convergence for High-Performance Thermoelectrics.

Multiband convergence has attracted significant interest due to its positive effects on further improving thermoelectric performance. However, the current research mainly focuses on two- or three-band convergence in lead chalcogenides through doping and alloying. Therefore, exploring a new strategy to facilitate more-band convergence has instructive significance and practical value in thermoelectric research. Herein, we first propose a high-entropy strategy to achieve four-band convergence for optimizing thermoelectric performance. Taking high-entropy AgSbPbSnGeTe5 as an example, we found that the emergence of more-band convergence occurs as the configuration entropy increases; in particular, the four-band convergence occurs in high-entropy AgSbPbSnGeTe5. The overlap of multiatom orbitals in the high-entropy sample contributes to the convergence of four valence bands, promoting the improvement of electrical performance. Meanwhile, due to large lattice distortion and disordered atoms, the phonon mean free path is effectively compressed, resulting in low lattice thermal conductivity of high-entropy AgSbPbSnGeTe5. Consequently, AgSbPbSnGeTe5 achieved an intrinsically high ZT value of 1.22 at 673 K, providing a cornerstone for further optimizing thermoelectric performance. For example, by generally optimizing the carrier concentration, a peak ZT value of ∼1.75 at 723 K is achieved. These insights offer a comprehensive understanding of the band structure affected by unique structures of high-entropy materials and also shed useful light on innovation mechanisms and functionalities for future improvement of thermoelectric performance.

Interlayer Phonon Coupling from Heavy and Light Sublayers in a Natural Van der Waals Superlattice.

Layered compounds characterized by van der Waals gaps are often associated with relatively weak interlayer particle interactions. However, in specific scenarios, these seemingly feeble forces can exert an impact on interlayer interactions through subtle energy fluctuations, which can give rise to a diverse range of physical and chemical properties, particularly intriguing in the context of thermal transport. In this study, taking a natural superlattice composed of alternately stacked PbS and SnS2 sublayers as a model, we proposed that in a superlattice, there is strong hybridization between acoustic phonons of heavy sublayers and optical phonons of light sublayers. We identified newly generated vibration modes in the superlattice, such as interlayer shear and breathing, which exhibit lower sound velocity and contribute less to heat transport compared to their parent materials, which significantly alters the thermal behaviors of the superlattice compared to its bulk counterparts. Our findings on the behavior of interlayer phonons in superlattices not only can shed light on developing functional materials with enhanced thermal dissipation capabilities but also contribute to the broader field of condensed matter physics, offering insights into various fields, including thermoelectrics and phononic devices, and may pave the way for technological advancements in these areas.

Genomic Insights into Adaptation to Karst Limestone and Incipient Speciation in East Asian Platycarya spp. (Juglandaceae).

When challenged by similar environmental conditions, phylogenetically distant taxa often independently evolve similar traits (convergent evolution). Meanwhile, adaptation to extreme habitats might lead to divergence between taxa that are otherwise closely related. These processes have long existed in the conceptual sphere, yet molecular evidence, especially for woody perennials, is scarce. The karst endemic Platycarya longipes, and its only congeneric species, P. strobilacea, which is widely distributed in the mountains in East Asia, provide an ideal model for examining the molecular basis of both convergent evolution and speciation. Using chromosome-level genome assemblies of both species, and whole genome resequencing data from 207 individuals spanning their entire distribution range, we demonstrate that P. longipes and P. strobilacea form two species-specific clades, which diverged around 2.09 million years ago. We find an excess of genomic regions exhibiting extreme interspecific differentiation, potentially due to long-term selection in P. longipes, likely contributing to the incipient speciation of the genus Platycarya. Interestingly, our results unveil underlying karst adaptation in both copies of the calcium influx channel gene TPC1 in P. longipes. TPC1 has previously been identified as a selective target in certain karst-endemic herbs, indicating a convergent adaptation to high calcium stress among karst-endemic species. Our study reveals the genic convergence of TPC1 among karst endemics, and the driving forces underneath the incipient speciation of the two Platycarya lineages.

Genomic Insights into Adaptation to Karst Limestone and Incipient Speciation in East Asian Platycarya spp. (Juglandaceae).

When challenged by similar environmental conditions, phylogenetically distant taxa often independently evolve similar traits (convergent evolution). Meanwhile, adaptation to extreme habitats might lead to divergence between taxa that are otherwise closely related. These processes have long existed in the conceptual sphere, yet molecular evidence, especially for woody perennials, is scarce. The karst endemic Platycarya longipes and its only congeneric species, Platycarya strobilacea, which is widely distributed in the mountains in East Asia, provide an ideal model for examining the molecular basis of both convergent evolution and speciation. Using chromosome-level genome assemblies of both species, and whole-genome resequencing data from 207 individuals spanning their entire distribution range, we demonstrate that P. longipes and P. strobilacea form two species-specific clades, which diverged around 2.09 million years ago. We find an excess of genomic regions exhibiting extreme interspecific differentiation, potentially due to long-term selection in P. longipes, likely contributing to the incipient speciation of the genus Platycarya. Interestingly, our results unveil underlying karst adaptation in both copies of the calcium influx channel gene TPC1 in P. longipes. TPC1 has previously been identified as a selective target in certain karst-endemic herbs, indicating a convergent adaptation to high calcium stress among karst-endemic species. Our study reveals the genic convergence of TPC1 among karst endemics and the driving forces underneath the incipient speciation of the two Platycarya lineages.

Element Diffusion Induced Carrier Transport Enhancement in High-Performance CZTSSe Self-Powered Photodetector.

Cu2ZnSn(S,Se)4 (CZTSSe) has attracted great interest in thin-film solar cells due to its excellent photoelectric performance in past decades, and recently is gradually expanding to the field of photodetectors. Here, the CZTSSe self-powered photodetector is prepared by using traditional photovoltaic device structure. Under zero bias, it exhibits the excellent performance with a maximum responsivity of 0.77 A W-1, a high detectivity of 8.78 × 1012 Jones, and a wide linear dynamic range of 103 dB. Very fast response speed with the rise/decay times of 0.576/1.792 µs, and ultra-high switching ratio of 3.54 × 105 are obtained. Comprehensive electrical and microstructure characterizations confirm that element diffusion among ITO, CdS, and CZTSSe layers not only optimizes band alignment of CdS/CZTSSe, but also suppresses the formation of interface defects. Such a suppression of interface defects and spike-like band alignment significantly inhibit carrier nonradiative recombination at interface and promote carrier transport capability. The low trap density in CZTSSe and low back contact barrier of CZTSSe/Mo could be responsible for the very fast response time of photodetector. This work definitely provides guidance for designing a high performance self-powered photodetector with high photoresponse, high switching ratio, fast response speed, and broad linear dynamic range.

Free-Breathing Compressed Sensing Cine Cardiac MRI for Assessment of Left Ventricular Strain by Feature Tracking in Children.

BACKGROUND: Cardiac MRI feature-tracking (FT) with breath-holding (BH) cine balanced steady state free precession (bSSFP) imaging is well established. It is unclear whether FT-strain measurements can be reliably derived from free-breathing (FB) compressed sensing (CS) bSSFP imaging. PURPOSE: To compare left ventricular (LV) strain analysis and image quality of an FB CS bSSFP cine sequence with that of a conventional BH bSSFP sequence in children. STUDY TYPE: Prospective. SUBJECTS: 40 children able to perform BHs (cohort 1 [12.1 ± 2.2 years]) and 17 children unable to perform BHs (cohort 2 [5.2 ± 1.8 years]). FIELD STRENGTH/SEQUENCE: 3T, bSSFP sequence with and without CS. ASSESSMENT: Acquisition times and image quality were assessed. LV myocardial deformation parameters were compared between BH cine and FB CS cine studies in cohort 1. Strain indices and image quality of FB CS cine studies were also assessed in cohort 2. Intraobserver and interobserver variability of strain parameters was determined. STATISTICAL TESTS: Paired t-test, Wilcoxon signed-rank test, intraclass correlation coefficient (ICC), and Bland-Altman analysis. A P-value <0.05 was considered statistically significant. RESULTS: In cohort 1, the mean acquisition time of the FB CS cine study was significantly lower than for conventional BH cine study (15.6 s vs. 209.4 s). No significant difference were found in global circumferential strain rate (P = 0.089), global longitudinal strain rate (P = 0.366) and EuroCMR image quality scores (P = 0.128) between BH and FB sequences in cohort 1. The overall image quality score of FB CS cine in cohort 2 was 3.5 ± 0.5 with acquisition time of 14.7 ± 2.1 s. Interobserver and intraobserver variabilities were good to excellent (ICC = 0.810 to 0.943). DATA CONCLUSION: FB CS cine imaging may be a promising alternative technique for strain assessment in pediatric patients with poor BH ability. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 1.

Pain trajectories and their associations with cognition among older adults: a 10-year cohort study from network perspective.

BACKGROUND: Few studies have examined the associations between pain trajectories and cognitive function in older adults. This study explored the associations between pain trajectories and different cognitive domains in older adults from a network perspective. METHODS: Data on pain trajectories were derived from the Health and Retirement Study between 2010 and 2020 using latent class growth analyses. Measurements of key cognition domains, including memory, attention, calculation, orientation and language, were included. Linear regression and network analysis were performed to evaluate the associations between different pain trajectories and cognition. RESULTS: A total of 9,551 older adults were included in this study and three trajectories of pain were identified. After controlling for the covariates, persistent severe pain trajectory was associated with poorer overall cognition, memory and calculation ability when compared to mild or non-persistent pain trajectory. In the pain and cognition network model, memory (expected influence (EI) = 0.62), language (EI = 0.58) and calculation (EI = 0.41) were the most central domains. CONCLUSIONS: Pain trajectories appeared stable over time among older adults in this study. Severity of persistent pain was an important risk factor for poor cognition, especially in relation to memory and calculation domains. Interventions targeting memory, language and calculation domains might be useful in addressing cognitive decline in older adults with persistent pain.

FHL3 promotes the formation of fast glycolytic muscle fibers by interacting with YY1 and muscle glycolytic metabolism.

The proportions of the various muscle fiber types are important in the regulation of skeletal muscle metabolism, as well as animal meat production. Four-and-a-half LIM domain protein 3 (FHL3) is highly expressed in fast glycolytic muscle fibers and differentially regulates the expression of myosin heavy chain (MyHC) isoforms at the cellular level. Whether FHL3 regulates the transformation of muscle fiber types in vivo and the regulatory mechanism is unclear. In this study, muscle-specific FHL3 transgenic mice were generated by random integration, and lentivirus-mediated gene knockdown or overexpression in muscles of mice or pigs was conducted. Functional analysis showed that overexpression of FHL3 in muscles significantly increased the proportion of fast-twitch myofibers and muscle mass but decreased muscle succinate dehydrogenase (SDH) activity and whole-body oxygen consumption. Lentivirus-mediated FHL3 knockdown in muscles significantly decreased muscle mass and the proportion of fast-twitch myofibers. Mechanistically, FHL3 directly interacted with the Yin yang 1 (YY1) DNA-binding domain, repressed the binding of YY1 to the fast glycolytic MyHC2b gene regulatory region, and thereby promoted MyHC2b expression. FHL3 also competed with EZH2 to bind the repression domain of YY1 and reduced H3K27me3 enrichment in the MyHC2b regulatory region. Moreover, FHL3 overexpression reduced glucose tolerance by affecting muscle glycolytic metabolism, and its mRNA expression in muscle was positively associated with hemoglobin A1c (HbA1c) in patients with type 2 diabetes. Therefore, FHL3 is a novel potential target gene for the treatment of muscle metabolism-related diseases and improvement of animal meat production.

Genomic insights into biased allele loss and increased gene numbers after genome duplication in autotetraploid Cyclocarya paliurus.

BACKGROUND: Autopolyploidy is a valuable model for studying whole-genome duplication (WGD) without hybridization, yet little is known about the genomic structural and functional changes that occur in autopolyploids after WGD. Cyclocarya paliurus (Juglandaceae) is a natural diploid-autotetraploid species. We generated an allele-aware autotetraploid genome, a chimeric chromosome-level diploid genome, and whole-genome resequencing data for 106 autotetraploid individuals at an average depth of 60 × per individual, along with 12 diploid individuals at an average depth of 90 × per individual. RESULTS: Autotetraploid C. paliurus had 64 chromosomes clustered into 16 homologous groups, and the majority of homologous chromosomes demonstrated similar chromosome length, gene numbers, and expression. The regions of synteny, structural variation and nonalignment to the diploid genome accounted for 81.3%, 8.8% and 9.9% of the autotetraploid genome, respectively. Our analyses identified 20,626 genes (69.18%) with four alleles and 9191 genes (30.82%) with one, two, or three alleles, suggesting post-polyploid allelic loss. Genes with allelic loss were found to occur more often in proximity to or within structural variations and exhibited a marked overlap with transposable elements. Additionally, such genes showed a reduced tendency to interact with other genes. We also found 102 genes with more than four copies in the autotetraploid genome, and their expression levels were significantly higher than their diploid counterparts. These genes were enriched in enzymes involved in stress response and plant defense, potentially contributing to the evolutionary success of autotetraploids. Our population genomic analyses suggested a single origin of autotetraploids and recent divergence (~ 0.57 Mya) from diploids, with minimal interploidy admixture. CONCLUSIONS: Our results indicate the potential for genomic and functional reorganization, which may contribute to evolutionary success in autotetraploid C. paliurus.

Improving physicochemical characteristics and cytotoxicity of baicalin esters by liposome encapsulation.

The instability of ester bonds, low water solubility, and increased cytotoxicity of flavonoid glycoside esters significantly limit their application in the food industry. Therefore, the present study attempted to resolve these issues through liposome encapsulation. The results showed that baicalin butyl ester (BEC4) and octyl ester (BEC8) have higher encapsulation and loading efficiencies and lower leakage rate from liposomes than baicalin. FTIR results revealed the location of BEC4 and BEC8 in the hydrophobic layer of liposomes, which was different from baicalin. Additionally, liposome encapsulation improved the water solubility and stability of BEC4 and BEC8 in the digestive system and PBS but significantly reduced their cytotoxicity. Furthermore, the release rate of BEC4 and BEC8 from liposomes was lower than that of baicalin during gastrointestinal digestion. These results indicate that liposome encapsulation alleviated the negative effects of fatty chain introduction into flavonoid glycosides.

Loss of RAGE prevents chronic intermittent hypoxia-induced nonalcoholic fatty liver disease via blockade of NF-кB pathway.

In recent years, receptor for advanced glycation end-products (RAGE) has been documented to induce liver fibrosis and inflammatory reaction. Further, microarray data analysis of this study predicted high expression of RAGE in non-alcoholic fatty liver disease (NAFLD). However, its specific mechanisms remain to be elucidated. Hence, this study is aimed at investigating the mechanistic insights of RAGE in chronic intermittent hypoxia (CIH)-induced NAFLD. ApoE knockout (ApoE-/-) mice were exposed to CIH to induce NAFLD, and primary hepatocytes were also exposed to CIH to mimic in vitro setting. Accordingly, we found that RAGE and NF-κB were upregulated in the liver tissues of CIH-induced NAFLD mice and CIH-exposed hepatocytes. Depleted RAGE attenuated CIH-induced hepatocyte injury, lipid deposition, and inflammation. The relationship between RAGE and NF-κB was analyzed by in silico analysis and correlation analysis. It was demonstrated that knockdown of RAGE inhibited the NF-кB pathway, thus alleviating CIH-induced disorders in hepatocytes. Moreover, in vivo experiments also verified that depletion of RAGE alleviated CIH-induced NAFLD by inhibiting NF-кB pathway. Collectively, loss of RAGE blocked the NF-кB pathway to alleviate CIH-induced NAFLD, therefore, highlighting a potential hepatoprotective target for treating NAFLD.

Dead-End Hybridization in Walnut Trees Revealed by Large-Scale Genomic Sequence Data.

Although hybridization plays a large role in speciation, some unknown fraction of hybrid individuals never reproduces, instead remaining as genetic dead-ends. We investigated a morphologically distinct and culturally important Chinese walnut, Juglans hopeiensis, suspected to have arisen from hybridization of Persian walnut (J. regia) with Asian butternuts (J. cathayensis, J. mandshurica, and hybrids between J. cathayensis and J. mandshurica). Based on 151 whole-genome sequences of the relevant taxa, we discovered that all J. hopeiensis individuals are first-generation hybrids, with the time for the onset of gene flow estimated as 370,000 years, implying both strong postzygotic barriers and the presence of J. regia in China by that time. Six inversion regions enriched for genes associated with pollen germination and pollen tube growth may be involved in the postzygotic barriers that prevent sexual reproduction in the hybrids. Despite its long-recurrent origination and distinct traits, J. hopeiensis does not appear on the way to speciation.

Integrative analysis of genomic and epigenomic data reveal underlying superenhancer-mediated microRNA regulatory network for human bone mineral density.

Bone mineral density (BMD) is a highly heritable complex trait and is a key indicator for diagnosis and treatment for osteoporosis. In the last decade, numerous susceptibility loci for BMD and fracture have been identified by genome-wide association studies (GWAS); however, fine mapping of these loci is challengeable. Here, we proposed a new long-range fine-mapping approach that combined superenhancers (SEs) and microRNAs (miRNAs) data, which were two important factors in control of cell identity and specific differentiation, with the GWAS summary datasets in cell-type-restricted way. Genome-wide SE-based analysis found that the BMD-related variants were significantly enriched in the osteoblast SE regions, indicative of potential long-range effects of such SNPs. With the SNP-mapped SEs (mSEs), 13 accessible long-range mSE-interacted miRNAs (mSE-miRNAs) were identified by integrating osteoblast Hi-C and ATAC-seq data, including three known bone-related miRNAs (miR-132-3p, miR-212-3p and miR-125b-5p). The putative targets of the two newly identified mSE-miRNAs (miR-548aj-3p and miR-190a-3p) were found largely enriched in osteogenic-related pathway and processes, suggesting that these mSE-miRNAs could be functional in the regulation of osteoblast differentiation. Furthermore, we identified 54 genes with the long-range 'mSE-miRNA' approach, and 24 of them were previously reported to be related to skeletal development. Besides, enrichment analysis found that these genes were specifically enriched in the post-transcriptional regulation and bone formation processes. This study provided a new insight into the approach of fine-mapping of GWAS loci. A tool was provided for the genome-wide SE-based analysis and the detection of long-range osteoblast-restricted mSE-miRNAs (https://github.com/Zheng-Lab-Westlake/Osteo-Fine-Mapp-SNP2SE2miRNA).

White matter changes in young and middle-aged males with chronic prostatitis/chronic pelvic pain syndrome: Tract-based spatial statistics analysis.

The supraspinal mechanism plays a key role in developing and maintaining chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). However, it is not clear how white matter changes in young and middle-aged males with CP/CPPS. In this cross-sectional study, 23 CP/CPPS patients and 22 healthy controls (HCs) were recruited. Tract-based spatial statistics was applied to investigate the differences in diffusion tensor imaging metrics, including fractional anisotropy (FA), mean diffusion (MD), radial diffusion (RD) and axial diffusion (AD), between CP/CPPS patients and HCs. The study also examined the association between white matter alterations and clinical variables in patients using correlation analysis. Compared with HCs, patients showed decreased FA, MD, RD and AD in the body and genu of the corpus callosum and right anterior corona radiata. In addition, they showed increased FA along with decreased MD, RD and AD in the left posterior limb of the internal capsule (PLIC-L), left external capsule and left cerebral peduncle. The FA of PLIC-L was negatively correlated with disease duration (r = -.54, corrected p = .017), while MD and RD were positively correlated (r = .45, corrected p = .042; r = .57, corrected p = .017). These results suggest that CP/CPPS is associated with extensive changes in white matter tracts, which are involved in pain processing. In particular, the FA, MD and RD values in the PLIC-L were correlated with the disease duration, indicating that the long-term course of CP/CPPS may have effects on the white matter microstructure of the pain perception pathways.

Synovial Oxygenation at Photoacoustic Imaging to Assess Rheumatoid Arthritis Disease Activity.

Background Synovial hypoxia is a hallmark of rheumatoid arthritis (RA). Photoacoustic (PA) imaging, based on the use of laser-generated US, can detect the oxygenation status of tissue in individuals with RA. However, large studies are lacking, with few investigating the correlation between oxygenation status and disease activity. Purpose To measure synovial oxygenation status in participants with RA by using a multimodal PA US imaging system and to determine the correlation between PA imaging-measured oxygen saturation (SO2) and disease activity. Materials and Methods In this prospective observational cohort study, multimodal PA US imaging examinations were performed on small joints of consecutive participants with RA, who were treated at two outpatient rheumatology clinics from 2019 to 2021, and healthy controls. The SO2 values of the synovium were measured with dual-wavelength PA imaging and classified into three categories-hyperoxia, intermediate oxygenation status, or hypoxia-based on the signal coloration and clustering analysis of the SO2 values. The correlations of oxygenation status with power Doppler US (PDUS) scoring and clinical disease activity index were evaluated with one-way analysis of variance and the Kruskal-Wallis test with Bonferroni correction. Results A total of 118 participants with RA (median age, 55 years [IQR, 41-62 years]; 92 women) and 15 healthy control participants (median age, 37 years [IQR, 33-41 years]; 11 women) were included. The wrist synovium was categorized as hyperoxic in 36 participants with RA, of intermediate oxygenation status in 48 participants, and hypoxic in 34 participants. All control participants had hyperoxic synovial tissues. For participants with RA, hyperoxic synovium had more affluent Doppler US-depicted vasculature than those with hypoxia and intermediate oxygenation status (mean PDUS grade: hyperoxia, 2.7 ± 0.6 [SD]; intermediate, 1.3 ± 0.7; hypoxia, 1.1 ± 0.8; P < .001). Participants with intermediate status synovium had a lower clinical disease activity index than those with hypoxia (intermediate, 11.0 [IQR, 5.0-21.5] vs hypoxia, 26.0 [IQR, 18.0-39.0]; P = .001). Conclusion Photoacoustic imaging-detected hypoxia in thickened synovium correlated with less vascularization and higher disease activity in participants with rheumatoid arthritis. Clinical trial registration no. NCT04297475 © RSNA, 2022 Online supplemental material is available for this article.

HDAC inhibitor ITF2357 reduces resistance of mutant-KRAS non-small cell lung cancer to pemetrexed through a HDAC2/miR-130a-3p-dependent mechanism.

BACKGROUND: Histone deacetylases (HDAC) contribute to oncogenic program, pointing to their inhibitors as a potential strategy against cancers. We, thus, studied the mechanism of HDAC inhibitor ITF2357 in resistance of mutant (mut)-KRAS non-small cell lung cancer (NSCLC) to pemetrexed (Pem). METHODS: We first determined the expression of NSCLC tumorigenesis-related HDAC2 and Rad51 in NSCLC tissues and cells. Next, we illustrated the effect of ITF2357 on the Pem resistance in wild type-KARS NSCLC cell line H1299, mut-KARS NSCLC cell line A549 and Pem-resistant mut-KARS cell line A549R in vitro and in xenografts of nude mice in vivo. RESULTS: Expression of HDAC2 and Rad51 was upregulated in NSCLC tissues and cells. Accordingly, it was revealed that ITF2357 downregulated HDAC2 expression to diminish the resistance of H1299, A549 and A549R cells to Pem. HDAC2 bound to miR-130a-3p to upregulate its target gene Rad51. The in vitro findings were reproduced in vivo, where ITF2357 inhibited the HDAC2/miR-130a-3p/Rad51 axis to reduce the resistance of mut-KRAS NSCLC to Pem. CONCLUSION: Taken together, HDAC inhibitor ITF2357 restores miR-130a-3p expression by inhibiting HDAC2, thereby repressing Rad51 and ultimately diminishing resistance of mut-KRAS NSCLC to Pem. Our findings suggested HDAC inhibitor ITF2357 as a promising adjuvant strategy to enhance the sensitivity of mut-KRAS NSCLC to Pem.

Concurrent large spontaneous portosystemic shunt embolization for the prevention of overt hepatic encephalopathy after TIPS: A randomized controlled trial.

BACKGROUND AND AIMS: Large spontaneous portosystemic shunt (SPSS) is associated with increased risk of HE in patients undergoing transjugular intrahepatic portosystemic shunt (TIPS). This study aimed to evaluate whether prophylactic embolization of large SPSS at the time of TIPS creation could reduce the incidence of post-TIPS HE in patients with cirrhosis and variceal bleeding. APPROACH AND RESULTS: From June 2014 to August 2017, 56 patients with cirrhosis and large SPSS planning to undergo TIPS for the prevention of variceal bleeding were randomly assigned (1:1) to receive TIPS alone (TIPS group, n = 29) or TIPS plus simultaneous SPSS embolization (TIPS+E group, n = 27). The primary endpoint was overt HE. TIPS placement and SPSS embolization was successful in all patients. During a median follow-up of 24 months, the primary endpoint was met in 15 patients (51.7%) in the TIPS group and six patients (22.2%) in the TIPS+E group (p = 0.045). The 2-year cumulative incidence of overt HE was significantly lower in the TIPS+E group compared with the TIPS group (21.2% vs. 48.3%; HR, 0.38; 95% CI, 0.15-0.97; p = 0.043). The 2-year incidence of recurrent bleeding (TIPS+E vs. TIPS, 15.4% vs. 25.1%; p = 0.522), shunt dysfunction (12.3% vs. 18.6%, p = 0.593), death (15.0% vs. 6.9%, p = 0.352), and other adverse events was not significantly different between the two groups. CONCLUSIONS: In patients with cirrhosis treated with TIPS for variceal bleeding, concurrent large SPSS embolization reduced the risk for overt HE without increasing other complications. Concurrent large SPSS embolization should therefore be considered for prophylaxis of post-TIPS HE.

Evaluation of coronary microvascular dysfunction and risk factors in children and youth with Turner syndrome by magnetic resonance myocardial perfusion imaging.

OBJECTIVE: Turner syndrome (TS) has an increased predisposition to ischaemic heart disease and the status of coronary microcirculation in TS is largely unknown. This study aims to evaluate myocardial microvascular function in TS using first-pass magnetic resonance perfusion imaging and determine significant risk factors contributing to microvascular dysfunction in the early stage. DESIGN: Perspective cohort study. PATIENTS: The study cohort consisted of 67 children and youth with TS and 32 age- and gender-matched controls. Measurements Clinical characteristics, left ventricle (LV) volume and function and cardiovascular magnetic resonance-derived myocardial perfusion parameters were assessed. Univariable and multivariable linear regression analyses were performed to assess the potential risk factors for microvascular dysfunction. RESULT: Microvascular perfusion decreased in TS in global and segmented myocardium as reflected in the lower upslopecor and maximum signal intensity (MaxSI) of LV myocardium compared to controls. Multivariable linear regression analysis indicated that age (ß = -0.107, 95% confidence interval [CI] = -0.201 to -0.013, p = .026) and being overweight/obese (ß = -1.155, CI = -2.134 to -0.176, p = .021) were independent impact factors of microvascular dysfunction. Subgroup analysis showed the upslopecor of older patients with TS decreased more significantly compared with that of normal controls. Upslopecor and MaxSI were lower in overweight/obese patients with TS than in patients with normal body mass index (BMI) and controls. CONCLUSION: Myocardial microvascular dysfunction can occur in children and youth patients with TS. Age and overweight/obesity were the independent risk factors of microvascular dysfunction, which imply the importance of lowering BMI for the prevention of coronary heart disease in young TS population.