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Abstract Background The atherogenic index of plasma (AIP) is considered an independent risk factor for coronary artery disease (CAD). The present study investigated whether AIP correlates with the formation of coronary collateral circulation (CCC) in CAD patients with chronic total occlusion (CTO). Methods This retrospective study included 1093 CAD patients with CTO confirmed by coronary angiography from January 2020 to December 2020 at Beijing Anzhen Hospital. Based on the Rentrop scoring system, the patients were divided into the good CCC group and the poor CCC group. AIP was calculated by log (triglyceride/high-density lipoprotein cholesterol). Meanwhile, the study population was further divided into four groups according to the quartiles of AIP. Results Patients in the poor CCC group exhibited significantly higher AIP compared to those in the good CCC group (0.31 ± 0.27 vs. 0.14 ± 0.24, p

Abstract Postzygotic reproductive isolation, which results in the irreversible divergence of species, is commonly accompanied by hybrid sterility, necrosis/weakness, or lethality in the F1 or other offspring generations. Here we show that the loss of function of HWS1 and HWS2, a couple of duplicated paralogs, together confer complete interspecific incompatibility between Asian and African rice. Both of these non-Mendelian determinants encode the putative Esa1-associated factor 6 (EAF6) protein, which functions as a characteristic subunit of the histone H4 acetyltransferase complex regulating transcriptional activation via genome-wide histone modification. The proliferating tapetum and inappropriate polar nuclei arrangement cause defective pollen and seeds in F2 hybrid offspring due to the recombinant HWS1/2-mediated misregulation of vitamin (biotin and thiamine) metabolism and lipid synthesis. Evolutionary analysis of HWS1/2 suggests that this gene pair has undergone incomplete lineage sorting (ILS) and multiple gene duplication events during speciation. Our findings have not only uncovered a pair of speciation genes that control hybrid breakdown but also illustrate a passive mechanism that could be scaled up and used in the guidance and optimization of hybrid breeding applications for distant hybridization.

Rice panicle architecture dominates grain yield. In this study, the authors demonstrate a method for rationally overcoming the trade-off between yield traits and optimizing rice panicle architecture by specifically manipulating ligand–receptor pairs.

Abstract The surgical timing after neoadjuvant androgen‐deprivation therapy (ADT) plus abiraterone acetate (AA) for patients with locally advanced or metastatic prostate cancer (PCa) is unknown. We divided patients with locally advanced or metastatic PCa into three groups according to prostate‐specific antigen (PSA) nadir after neoadjuvant ADT plus AA: group 1 (PSA ≤ 0.2 ng/ml), group 2 (0.2 4.0 ng/ml).The median PSA baseline levels in groups 1, 2, 3 were 118.42 (32.03–457.78), 143.48 (17.7–8100.16), and153.35 (46.44–423.31) ng/ml, respectively. The median times of progression to CRPC in groups 1, 2,and 3 were 30, 26, and 26 months, respectively. Compared to patients with PSA nadir >0.2 ng/ml, patients with PSA nadir

Zhang et al. report QTL GS3.1 as regulating rice grain size via metabolic flux allocation between two branches of phenylpropanoid metabolism. Their results identify the biosynthetic pathway for grain size regulation via a multidrug and toxic compounds extrusion transporter, and demonstrate enlarged grains, reduced flavonoid content, and increased lignin content in the panicles with GS3.1.

Global warming threatens food security. Rice (Oryza sativa L.), a vital food crop, is vulnerable to heat stress, especially at the reproductive stage. Here we summarize putative mechanisms of high-temperature perception (via RNA secondary structure, the phyB gene, and phase separation) and response (membrane fluidity, heat shock factors, heat shock proteins, and ROS (reactive oxygen species) scavenging) in plants. We describe how rice responds to heat stress at different cell-component levels (membrane, endoplasmic reticulum, chloroplasts, and mitochondria) and functional levels (denatured protein elimination, ROS scavenging, stabilization of DNA and RNA, translation, and metabolic flux changes). We list temperature-sensitive genetic male sterility loci available for use in rice hybrid breeding and explain the regulatory mechanisms associated with some of them. Breeding thermotolerant rice species without yield penalties via natural alleles mining and transgenic editing should be the focus of future work.

Abstract Adult‐type granulosa cell tumors (aGCTs) account for 90% of malignant ovarian sex cord‐stromal tumors and 2–5% of all ovarian cancers. These tumors are usually diagnosed at an early stage and are treated with surgery. However, one‐third of patients relapse between 4 and 8 years after initial diagnosis, and there are currently no effective treatments other than surgery for these relapsed patients. As the majority of aGCTs (>95%) harbor a somatic mutation in FOXL2 (c.C402G; p.C134W), the aim of this study was to identify genetic mutations besides FOXL2 C402G in aGCTs that could explain the clinical diversity of this disease. Whole‐genome sequencing of 10 aGCTs and their matched normal blood was performed to identify somatic mutations. From this analysis, a custom amplicon‐based panel was designed to sequence 39 genes of interest in a validation cohort of 83 aGCTs collected internationally. KMT2D inactivating mutations were present in 10 of 93 aGCTs (10.8%), and the frequency of these mutations was similar between primary and recurrent aGCTs. Inactivating mutations, including a splice site mutation in candidate tumor suppressor WNK2 and nonsense mutations in PIK3R1 and NLRC5, were identified at a low frequency in our cohort. Missense mutations were identified in cell cycle‐related genes TP53, CDKN2D, and CDK1. From these data, we conclude that aGCTs are comparatively a homogeneous group of tumors that arise from a limited set of genetic events and are characterized by the FOXL2 C402G mutation. Secondary mutations occur in a subset of patients but do not explain the diverse clinical behavior of this disease. As the FOXL2 C402G mutation remains the main driver of this disease, progress in the development of therapeutics for aGCT would likely come from understanding the functional consequences of the FOXL2 C402G mutation.

Abstract Background Global simultaneous recording of atrial activation during atrial fibrillation (AF) can elucidate underlying mechanisms contributing to AF maintenance. A better understanding of these mechanisms may allow for an individualized ablation strategy to treat persistent AF. The study aims to characterize left atrial endocardial activation patterns during AF using noncontact charge‐density mapping. Methods Twenty‐five patients with persistent AF were studied. Activation patterns were characterized into three subtypes: (i) focal with centrifugal activation (FCA); (ii) localized rotational activation (LRA); and (iii) localized irregular activation (LIA). Continuous activation patterns were analyzed and distributed in 18 defined regions in the left atrium. Results A total of 144 AF segments with 1068 activation patterns were analyzed. The most common pattern during AF was LIA (63%) which consists of four disparate features of activation: slow conduction (45%), pivoting (30%), collision (16%), and acceleration (7%). LRA was the second‐most common pattern (20%). FCA accounted for 17% of all activations, arising frequently from the pulmonary veins (PVs)/ostia. A majority of patients (24/25; 96%) showed continuous and highly dynamic patterns of activation comprising multiple combinations of FCA, LRA, and LIA, transitioning from one to the other without a discernible order. Preferential conduction areas were typically seen in the mid‐anterior (48%) and lower‐posterior (40%) walls. Conclusion Atrial fibrillation is characterized by heterogeneous activation patterns identified in PV‐ostia and non‐PV regions throughout the LA at varying locations between individuals. Clinical implications of individualized ablation strategies guided by charge‐density mapping need to be determined.

Increasing grain yield needs to be put in the context of environmental stress. Here, the authors reveal that a UDP-glucosyltransferase is associated with regulation of rice grain size, abiotic stress tolerance, flavonoid-mediated auxin signaling, and redirection of carbon flux to flavonoid glycosides synthesis.

Prostate cancer is a common malignant tumor and the second leading cause of cancer-related death in men. Radiation therapy is a curative treatment for localized prostate cancer and has a limited effect for castration-resistant prostate cancer (CRPC). Interleukin 24 (IL-24) has a radiosensitizing effect in cancer cells. Our previous studies showed that ZD55-IL-24, an oncolytic adenovirus harboring IL-24, had better anti-tumor effect with no toxicity to normal cells. In this study, we evaluated the synergistic anti-tumor effect of oncolytic adenovirus ZD55-IL-24 combined with radiotherapy in prostate cancer. In Vitro and In Vivo experiments showed that the combined therapy significantly inhibited the growth of prostate cancer and provoked apoptosis of prostate cancer cells. In conclusion, the combination of ionizing radiation and oncolytic adenovirus expressing IL24 could achieve synergistic anti-tumor effect on prostate cancer, and is a promising strategy for prostate cancer therapy.

Mutation signatures in cancer genomes reflect endogenous and exogenous mutational processes, offering insights into tumour etiology, features for prognostic and biologic stratification and vulnerabilities to be exploited therapeutically. We present a novel machine learning formalism for improved signature inference, based on multi-modal correlated topic models (MMCTM) which can at once infer signatures from both single nucleotide and structural variation counts derived from cancer genome sequencing data. We exemplify the utility of our approach on two hormone driven, DNA repair deficient cancers: breast and ovary (n = 755 samples total). We show how introducing correlated structure both within and between modes of mutation can increase accuracy of signature discovery, particularly in the context of sparse data. Our study emphasizes the importance of integrating multiple mutation modes for signature discovery and patient stratification, and provides a statistical modeling framework to incorporate additional features of interest for future studies.

We develop a new regression algorithm, cMIKANA, for inference of gene regulatory networks from combinations of steady-state and time-series gene expression data. Using simulated gene expression datasets to assess the accuracy of reconstructing gene regulatory networks, we show that steady-state and time-series data sets can successfully be combined to identify gene regulatory interactions using the new algorithm. Inferring gene networks from combined data sets was found to be advantageous when using noisy measurements collected with either lower sampling rates or a limited number of experimental replicates. We illustrate our method by applying it to a microarray gene expression dataset from human umbilical vein endothelial cells (HUVECs) which combines time series data from treatment with growth factor TNF and steady state data from siRNA knockdown treatments. Our results suggest that the combination of steady-state and time-series datasets may provide better prediction of RNA-to-RNA interactions, and may also reveal biological features that cannot be identified from dynamic or steady state information alone. Finally, we consider the experimental design of genomics experiments for gene regulatory network inference and show that network inference can be improved by incorporating steady-state measurements with time-series data.

Utilizing observed wind speed and direction data from observation stations near the Taiwan Strait and ocean buoys, along with forecast data from the EC model, GRAPES_GFS model, and PanGu weather prediction model within the same period, RMSE, MAE, CC, and other parameters were calculated. To comparatively evaluate the forecasting performance of the PanGu weather prediction model on the sea surface wind field near the Taiwan Strait from 00:00 on 1 June 2023, to 23:00 on 31 May 2024. The PanGu weather prediction model is further divided into the ERA5 (PanGu) model driven by ERA5 initial fields and the GRAPES_GFS (PanGu) model driven by GRAPES_GFS initial fields. The main conclusions are as follows: (1) over a one-year evaluation period, for wind speed forecasts with lead times of 0 h to 120 h in the Taiwan Strait region, the overall forecasting skill of the PanGu weather prediction model is superior to that of the model forecasts; (2) different initial fields input into the PanGu weather prediction model lead to different final forecast results, with better initial field data corresponding to forecast results closer to observations, thus indicating the operational transferability of the PanGu model in smaller regions; (3) regarding forecasts of wind speed categories, the credibility of the results is high when the wind speed level is ≤7, and the PanGu weather prediction model performs better among similar forecasts; (4) although the EC model's wind direction forecasts are closer to the observation field results, the PanGu weather forecasting model also provides relatively accurate and rapid forecasts of the main wind directions within a shorter time frame. [ABSTRACT FROM AUTHOR]

Cardiovascular disease remains the leading cause of mortality in women, yet it has not raised the awareness from the public. The pathogenesis of cardiovascular disease differs significantly between females and males concerning the effect of sex hormones. Estrogen and progestogen impact cardiovascular system through genomic and non-genomic effects. Before menopause, cardiovascular protective effects of estrogens have been well described. Progestogens were often used in combination with estrogens in hormone therapy. Fluctuations in sex hormone levels, particularly estrogen deficiency, were considered the specific risk factor in women's cardiovascular disease. However, considerable heterogeneity in the impact of hormone therapy was observed in clinical trials. The heterogeneity is likely closely associated with factors such as the initial time, administration route, dosage, and formulation of hormone therapy. This review will delve into the pathogenesis and hormone therapy, summarizing the effect of female sex hormones on hypertension, pre-eclampsia, coronary heart disease, heart failure with preserved ejection fraction, and cardiovascular risk factors specific to women. [ABSTRACT FROM AUTHOR]

Endometriosis is a significant risk factor for clear cell and endometrioid ovarian cancers and is often found contiguous with these cancers. Using whole-genome shotgun sequencing of seven clear cell ovarian carcinomas (CCC) and targeted sequencing in synchronous endometriosis, we have investigated how this carcinoma may evolve from endometriosis. In every case we observed multiple tumour-associated somatic mutations in at least one concurrent endometriotic lesion. ARID1A and PIK3CA mutations appeared consistently in concurrent endometriosis when present in the primary CCC. In several cases, one or more endometriotic lesions carried the near-complete complement of somatic mutations present in the index CCC tumour. Ancestral mutations were detected in both tumour-adjacent and -distant endometriotic lesions, regardless of any cytological atypia. These findings provide objective evidence that multifocal benign endometriotic lesions are clonally related and that CCCs arising in these patients progress from endometriotic lesions that may already carry sufficient cancer-associated mutations to be considered neoplasms themselves, albeit with low malignant potential. We speculate that genomically distinct classes of endometriosis exist and that ovarian endometriosis with high mutational burden represents one class at high risk for malignant transformation.

This study focused on correcting short-term wind speed forecasts extracted from GFS global forecast data sets at corresponding locations and heights. Data measurement mode and calibration method of the LiDAR data were discussed, and wind speed at three different heights (50m, 80m, and 100m) from floating LiDARs were employed. The results indicated that directly using the Kalman filter method with sliding adaptive weights to generate the average hysteresis deviation to correct the wind speed did not yield satisfactory results. Statistical analysis suggested that better standard deviation results can be obtained by lowering the ratio of the average hysteresis deviation in the forecast correction formula. When the average hysteresis deviation ratio was reduced to 0.1--0.5, the wind speed standard deviation after correction by the Kalman filtering method was generally lower than the wind speed standard deviation before correction, and the best ratio was 0.3. Using this hysteresis deviation ratio for wind speed correction at different forecast times and periods for these three LiDAR devices revealed that, except for individual data sets, more than 90% of the wind speed data sets exhibited reduced standard deviation after correction compared to the uncorrected data sets. After the introduction of this improved algorithm, the wind speed forecast improvement rate at each height ranged from 5% to 20%. [ABSTRACT FROM AUTHOR]