Search

Abstract Genome-wide association studies (GWAS) identified over fifty loci associated with lung cancer risk. However, underlying mechanisms and target genes are largely unknown, as most risk-associated variants might regulate gene expression in a context-specific manner. Here, we generate a barcode-shared transcriptome and chromatin accessibility map of 117,911 human lung cells from age/sex-matched ever- and never-smokers to profile context-specific gene regulation. Identified candidate cis-regulatory elements (cCREs) are largely cell type-specific, with 37% detected in one cell type. Colocalization of lung cancer candidate causal variants (CCVs) with these cCREs combined with transcription factor footprinting prioritize the variants for 68% of the GWAS loci. CCV-colocalization and trait relevance score indicate that epithelial and immune cell categories, including rare cell types, contribute to lung cancer susceptibility the most. A multi-level cCRE-gene linking system identifies candidate susceptibility genes from 57% of the loci, where most loci display cell-category-specific target genes, suggesting context-specific susceptibility gene function.

Abstract A wide variety of metabolic gene clusters exist in eukaryotic genomes, but fatty acid metabolic gene clusters have not been discovered. Here, combining with metabolic and phenotypic genome-wide association studies, we identify a major locus containing a six-gene fatty acid metabolic gene cluster on chromosome 3 (FGC3) that controls the cutin monomer hydroxymonoacylglycerols (HMGs) contents and rice yield, possibly through variation in the transcription of FGC3 members. We show that HMGs are sequentially synthesized in the endoplasmic reticulum by OsFAR2, OsKCS11, OsGPAT6, OsCYP704B2 and subsequently transported to the apoplast by OsABCG22 and OsLTPL82. Mutation of FGC3 members reduces HMGs, leading to defective male reproductive development and a significant decrease in yield. OsMADS6 and OsMADS17 directly regulate FGC3 and thus influence male reproduction and yield. FGC3 is conserved in Poaceae and likely formed prior to the divergence of Pharus latifolius. The eukaryotic fatty acid and plant primary metabolic gene cluster we identified show a significant impact on the origin and evolution of Poaceae and has potential for application in hybrid crop breeding.

Background Mosaic loss of chromosome Y (mLOY) in leukocytes of men reflects genomic instability from aging, smoking, and environmental exposures. A similar mosaic loss of chromosome X (mLOX) occurs among women. However, the associations between mLOY, mLOX, and risk of incident heart diseases are unclear. Methods and Results We estimated associations between mLOY, mLOX, and risk of incident heart diseases requiring hospitalization, including atrial fibrillation, myocardial infarction, ischemic heart disease, cardiomyopathy, and heart failure. We analyzed 190 613 men and 224 853 women with genotyping data from the UK Biobank. Among these participants, there were 37 037 men with mLOY and 13 978 women with mLOX detected using the Mosaic Chromosomal Alterations caller. Multivariable Cox regression was used to estimate hazard ratios (HRs) and 95% CIs of each incident heart disease in relation to mLOY in men and mLOX in women. Additionally, Mendelian randomization was conducted to estimate causal associations. Among men, detectable mLOY was associated with elevated risk of atrial fibrillation (HR, 1.06 [95% CI, 1.03–1.11]). The associations were apparent in both never smokers (HR, 1.07 [95% CI, 1.01–1.14]) and ever smokers (HR, 1.05 [95% CI, 1.01–1.11]) as well as men aged >60 and ≤60 years. Mendelian randomization analyses supported causal associations between mLOY and atrial fibrillation (HRMR‐PRESSO, 1.15 [95% CI, 1.13–1.18]). Among postmenopausal women, we found a suggestive inverse association between detectable mLOX and atrial fibrillation risk (HR, 0.90 [95% CI, 0.83–0.98]). However, associations with mLOY and mLOX were not found for other heart diseases. Conclusions Our findings suggest that mLOY and mLOX reflect sex‐specific biological processes or exposure profiles related to incident atrial fibrillation requiring hospitalization.

The shock resistance capability of ship power equipment is an important guarantee for the safe and stable operation of ships, and a reasonable evaluation method can be more convenient for obtaining the prediction results of power equipment shock resistance. First, the impact processes are divided into the low/high speed collision impact process and non-contact explosion impact process, and the non-integrated and integrated shock resistance methods of ship equipment are described in terms of the master-slave system. The research progress is then summarized and key research technologies in the field of shock resistance for ship power equipment are put forward. The non-integrated methods of ship equipment are divided into three categories, namely the equivalent static method, dynamic design analysis method and time-domain analysis method, and combined with the characteristics of integrated methods. It is concluded that the equivalent static method is only applicable to structurally simple power equipment with low frequency effects; the dynamic design analysis method neglects the effects of adjacent equipment, vibration isolation system and hull structure on impact input loads; and the time-domain analysis method is only applicable to specific scenarios or shock signal inputs such as explosive shocks. The integration of ship equipment takes into account the multi-degree-of-freedom system formed by the hull structure–base–vibration isolation system–equipment, and the calculation results are closer to the actual working condition data, but a large amount of resources is consumed in the modelling and calculation process. Finally, the author forecasts and summarizes important development directions for ship power equipment shock resistance, including the accurate selection of evaluation methods, reasonable improvement of shock resistance test rigs, extraction and analysis of impact response signals, analysis of the multi-field coupling effects of power equipment, simplification study of the physical models of power equipment, research on the equivalent substitution of internal flow media, and the combination of data mining and deep learning methods.

Noncontact optical thermometers have attracted widespread attention, but existing problems such as single-mode and low-sensitivity thermometers still urgently need to be solved. Herein, a novel multiple-mode thermometer was designed for the polymorphism LaSc3(BO3)4:Eu2+/3+,Li+. X-ray diffraction (XRD) patterns revealed a slight transition between α- and β-phases with the concentrations of the dopants, which is further proved by structure refinements and first-principles calculations. The coexistence of Eu2+ and Eu3+ in the phosphors and their relative percentages were confirmed by X-ray absorption near-edge structure (XANES) spectra. Benefiting from appropriate emissions from Eu2+ and Eu3+ without obvious energy transfer and their opposite changing trends with temperatures under 307 nm excitation, a triple-mode optical thermometer is obtained for this material within the temperature range of 150–450 K. The highest sensitivities of 27.65, 14.05, and 7.68 %·K−1 are achieved based on two fluorescence intensity ratio (FIR) modes of Eu2+ and Eu3+ (5d–4f/5D0–7F2,4) and the fluorescence lifetime (FL) mode of Eu2+, respectively. To the best of our knowledge, the former is almost the highest in Eu2+ and Eu3+ co-doped thermometers. These results indicate that this material may be used as an excellent multiple-mode optical thermometer.

As more multi-ancestry GWAS summary data become available, we have developed a comprehensive trans-ancestry pathway analysis framework that effectively utilizes this diverse genetic information. Within this framework, we evaluated various strategies for integrating genetic data at different levels-SNP, gene, and pathway-from multiple ancestry groups. Through extensive simulation studies, we have identified robust strategies that demonstrate superior performance across diverse scenarios. Applying these methods, we analyzed 6,970 pathways for their association with schizophrenia, incorporating data from African, East Asian, and European populations. Our analysis identified over 200 pathways significantly associated with schizophrenia, even after excluding genes near genome-wide significant loci. This approach substantially enhances detection efficiency compared to traditional single-ancestry pathway analysis and the conventional approach that amalgamates single-ancestry pathway analysis results across different ancestry groups. Our framework provides a flexible and effective tool for leveraging the expanding pool of multi-ancestry GWAS summary data, thereby improving our ability to identify biologically relevant pathways that contribute to disease susceptibility.

BackgroundGrowing evidence indicates a potential association between the gut microbiome and psoriasis. Nevertheless, the precise nature of these associations and whether they constitute causal relationships remain unclear.MethodsA rigorous bidirectional two-sample Mendelian randomization study was undertaken to establish a putative causal link between gut microbiota and psoriasis. We drew upon publicly available datasets containing summary statistics from GWAS to accomplish this. Utilizing various analytical techniques, including inverse variance weighting, MR-Egger, weighted median, weighted model, and MR-PRESSO, we sought to validate the putative causal association between gut microbiota and psoriasis. A reverse Mendelian randomization analysis was conducted to further investigate the relationship.ResultsAfter conducting a forward Mendelian randomization analysis, a causal relationship was established between 19 gut microbiota and psoriasis. Furthermore, the reverse MR study revealed causality between psoriasis and 13 gut microbiota. Notably, no substantial heterogeneity of instrumental variables or horizontal pleiotropy was observed.ConclusionThis research suggests a potential genetic association and causal nexus between gut microorganisms and psoriasis, indicating potential implications for the clinical management and therapy of psoriasis. Additional observational studies with a larger population sample size and animal model experiments are imperative to fully elucidate this association’s underlying mechanisms.

BackgroundIncreasing evidence suggests a robust correlation between the gut microbiome and alopecia areata. In light of the extensive diversity of gut microbiota, this study aims to utilize state-of-the-art and comprehensive data to explore the causative association between gut microbiota and alopecia areata.ObjectiveWe conducted a Mendelian randomization (MR)-based two-sample study to elucidate the causal relationship between gut microbiota and alopecia areata.MethodSummary information on Ncase = 767 and Ncontrol = 394,105 cases of alopecia areata was obtained from the FinnGen study. A total of 473 gut microbial taxa were summarized from the genome-wide association study (GWAS) catalog. The study comprised a forward Mendelian randomization (MR) analysis with the gut microbiome as the exposure factor and alopecia areata as the outcome, as well as a reverse MR analysis with alopecia areata as the exposure factor and the gut microbiome as the outcome. Various analytical methods including inverse variance weighting (IVW), Weighted Median, MR-Egger, Weighted Mode, and Simple Mode were employed. Subsequently, sensitivity analysis was conducted to ensure the robustness of our research findings.ResultThis study has established a causal relationship between gut microbiota and alopecia areata. Forward causal analysis revealed causality relationships between 16 gut microbial taxa and alopecia areata, while reverse causal analysis found that there may be a causal relationship between alopecia areata and 16 gut microbial taxa (not statistically significant).ConclusionOur study findings suggest a causal relationship between gut microbiota and alopecia areata, providing potential guidance for future clinical trials.

Abstract Floral organ shape and size in cereal crops can affect grain size and yield, so genes that regulate their development are promising breeding targets. The lemma, which protects inner floral organs, can physically constrain grain growth; while the awn, a needle-like extension of the lemma, creates photosynthate to developing grain. Although several genes and modules controlling grain size and awn/lemma growth in rice have been characterized, these processes, and the relationships between them, are not well understood for barley and wheat. Here, we demonstrate that the barley E-class gene HvMADS1 positively regulates awn length and lemma width, affecting grain size and weight. Cytological data indicates that HvMADS1 promotes awn and lemma growth by promoting cell proliferation, while multi-omics data reveals that HvMADS1 target genes are associated with cell cycle, phytohormone signaling, and developmental processes. We define two potential targets of HvMADS1 regulation, HvSHI and HvDL, whose knockout mutants mimic awn and/or lemma phenotypes of mads1 mutants. Additionally, we demonstrate that HvMADS1 interacts with APETALA2 (A-class) to synergistically activate downstream genes in awn/lemma development in barley. Notably, we find that MADS1 function remains conserved in wheat, promoting cell proliferation to increase awn length. These findings extend our understanding of MADS1 function in floral organ development and provide insights for Triticeae crop improvement strategies.

Abstract Male-pattern baldness (MPB) is related to dysregulation of androgens such as testosterone. A previously observed relationship between MPB and skin cancer may be due to greater exposure to ultraviolet radiation or indicate a role for androgenic pathways in the pathogenesis of skin cancers. We dissected this relationship via Mendelian randomization (MR) analyses, using genetic data from recent male-only meta-analyses of cutaneous melanoma (12,232 cases; 20,566 controls) and keratinocyte cancers (KCs) (up to 17,512 cases; >100,000 controls), followed by stratified MR analysis by body-sites. We found strong associations between MPB and the risk of KC, but not with androgens, and multivariable models revealed that this relationship was heavily confounded by MPB single nucleotide polymorphisms involved in pigmentation pathways. Site-stratified MR analyses revealed strong associations between MPB with head and neck squamous cell carcinoma and melanoma, suggesting that sun exposure on the scalp, rather than androgens, is the main driver. Men with less hair covering likely explains, at least in part, the higher incidence of melanoma in men residing in countries with high ambient UV.

Background Previous pandemics have had negative effects on mental health, but there are few data on children and adolescents who were receiving ongoing psychiatric treatment. Aims To study changes in emotions and clinical state, and their predictors, during the COVID-19 pandemic in France. Method We administered (by interview) the baseline Youth Self-Report version of the CoRonavIruS Health Impact Survey v0.3 (CRISIS, French translation) to 123 adolescent patients and the Parent/Caregiver version to evaluate 99 child patients before and during the first ‘lockdown’. For 139 of these patients who received ongoing treatment in our centre, treating physicians retrospectively completed longitudinal global ratings for five time periods, masked to CRISIS ratings. Results The main outcome measure was the sum of eight mood state items, which formed a single factor in each age group. Overall, this score improved for each age group during the first lockdown. Clinician ratings modestly supported this result in patients without intellectual disability or autism spectrum disorder. Improvement of mood states was significantly associated with perceived improvement in family relationships in both age groups. Conclusions Consistent with previous studies of clinical cohorts, our patients had diverse responses during the pandemic. Several factors may have contributed to the finding of improvement in some individuals during the first lockdown, including the degree of family support or conflict, stress reduction owing to isolation, limitations of the outcome measures and/or possible selection bias. Ongoing treatment may have had a protective effect. Clinically, during crises additional support may be needed by families who experience increased conflict or who care for children with intellectual disability.

Abstract Background The rule of thumb that there is little gain in statistical power by obtaining more than 4 controls per case, is based on type-1 error α = 0.05. However, association studies that evaluate thousands or millions of associations use smaller α and may have access to plentiful controls. We investigate power gains, and reductions in p-values, when increasing well beyond 4 controls per case, for small α. Methods We calculate the power, the median expected p-value, and the minimum detectable odds-ratio (OR), as a function of the number of controls/case, as α decreases. Results As α decreases, at each ratio of controls per case, the increase in power is larger than for α = 0.05. For α between 10–6 and 10–9 (typical for thousands or millions of associations), increasing from 4 controls per case to 10–50 controls per case increases power. For example, a study with power = 0.2 (α = 5 × 10–8) with 1 control/case has power = 0.65 with 4 controls/case, but with 10 controls/case has power = 0.78, and with 50 controls/case has power = 0.84. For situations where obtaining more than 4 controls per case provides small increases in power beyond 0.9 (at small α), the expected p-value can decrease by orders-of-magnitude below α. Increasing from 1 to 4 controls/case reduces the minimum detectable OR toward the null by 20.9%, and from 4 to 50 controls/case reduces by an additional 9.7%, a result which applies regardless of α and hence also applies to “regular” α = 0.05 epidemiology. Conclusions At small α, versus 4 controls/case, recruiting 10 or more controls/cases can increase power, reduce the expected p-value by 1–2 orders of magnitude, and meaningfully reduce the minimum detectable OR. These benefits of increasing the controls/case ratio increase as the number of cases increases, although the amount of benefit depends on exposure frequencies and true OR. Provided that controls are comparable to cases, our findings suggest greater sharing of comparable controls in large-scale association studies.

Abstract Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (Pinteraction = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications.

Line structured light (LSL) measurement systems can obtain high accuracy profiles, but the overall clarity relies greatly on the sampling interval of the scanning process. Photometric stereo (PS), on the other hand, is sensitive to tiny features but has poor geometrical accuracy. Cooperative measurement with these two methods is an effective way to ensure precision and clarity results. In this paper, an LSL-PS cooperative measurement system is brought out. The calibration methods used in the LSL and PS measurement system are given. Then, a data fusion algorithm with adaptive weights is proposed, where an error function that contains the 3D point cloud matching error and normal vector error is established. The weights, which are based on the angles of adjacent normal vectors, are also added to the error function. Afterward, the fusion results can be obtained by solving linear equations. From the experimental results, it can be seen that the proposed method has the advantages of both the LSL and PS methods. The 3D reconstruction results have the merits of high accuracy and high clarity.

Summary: Genetics have nominated many schizophrenia risk genes and identified convergent signals between schizophrenia and neurodevelopmental disorders. However, functional interpretation of the nominated genes in the relevant brain cell types is often lacking. We executed interaction proteomics for six schizophrenia risk genes that have also been implicated in neurodevelopment in human induced cortical neurons. The resulting protein network is enriched for common variant risk of schizophrenia in Europeans and East Asians, is down-regulated in layer 5/6 cortical neurons of individuals affected by schizophrenia, and can complement fine-mapping and eQTL data to prioritize additional genes in GWAS loci. A sub-network centered on HCN1 is enriched for common variant risk and contains proteins (HCN4 and AKAP11) enriched for rare protein-truncating mutations in individuals with schizophrenia and bipolar disorder. Our findings showcase brain cell-type-specific interactomes as an organizing framework to facilitate interpretation of genetic and transcriptomic data in schizophrenia and its related disorders.

Abstract This study presents a clock synchronization method based on quantum entanglement which is simple and reliable and more efficient. The clock synchronization method based on quantum entanglement scheme can greatly improve the accuracy and precision of measurement. More importantly, the proposed method avoids synchronization error caused by traditional method due to the asymmetry of two-way delay. The probability of measuring the quantum state oscillates in cosine or sine fashion with propagation delay. The final experimental and simulation results are basically consistent with the theoretical results. The clock synchronization method based on quantum entanglement scheme can greatly imrprove the accuracy and precision of measurement.

Background: Antidepressants are a first-line treatment for depression. However, only a third of individuals experience remission after the first treatment. Common genetic variation, in part, likely regulates antidepressant response, yet the success of previous genome-wide association studies has been limited by sample size. This study performs the largest genetic analysis of prospectively assessed antidepressant response in major depressive disorder to gain insight into the underlying biology and enable out-of-sample prediction. Methods: Genome-wide analysis of remission (nremit = 1852, nnonremit = 3299) and percentage improvement (n = 5218) was performed. Single nucleotide polymorphism–based heritability was estimated using genome-wide complex trait analysis. Genetic covariance with eight mental health phenotypes was estimated using polygenic scores/AVENGEME. Out-of-sample prediction of antidepressant response polygenic scores was assessed. Gene-level association analysis was performed using MAGMA and transcriptome-wide association study. Tissue, pathway, and drug binding enrichment were estimated using MAGMA. Results: Neither genome-wide association study identified genome-wide significant associations. Single nucleotide polymorphism–based heritability was significantly different from zero for remission (h2 = 0.132, SE = 0.056) but not for percentage improvement (h2 = −0.018, SE = 0.032). Better antidepressant response was negatively associated with genetic risk for schizophrenia and positively associated with genetic propensity for educational attainment. Leave-one-out validation of antidepressant response polygenic scores demonstrated significant evidence of out-of-sample prediction, though results varied in external cohorts. Gene-based analyses identified ETV4 and DHX8 as significantly associated with antidepressant response. Conclusions: This study demonstrates that antidepressant response is influenced by common genetic variation, has a genetic overlap schizophrenia and educational attainment, and provides a useful resource for future research. Larger sample sizes are required to attain the potential of genetics for understanding and predicting antidepressant response.

The reproductive development process of rice is not only important for basic developmental biology research, but also of great benefit to production practice. However, current understanding of the reproductive growth process is relatively limited, especially in the later stages of development. Here we report that OsGAMYBL2, a homologous gene of GAMYB, is required for pollen maturation and germination in rice, and that loss of function of OsGAMYBL2 leads to male sterility in rice. We generated three alleles of OsGAMYBL2 knockout mutants using CRISPR/Cas9 system, all of them lost fertility when grown in the paddy field. Semi-section and electron microscopy observations revealed that there are no visible morphological changes in the outer and inner surfaces of anther and in the surface of mature pollens between mutants and wild type. However, pollens at late developmental stages exhibited much lighter pollen viability staining and some of them shriveled. In vitro and in vivo germination experiments showed that mutant pollens fail to germinate, leading to abnormal pollen tube formation and subsequent defective pollination. Furthermore, we observed that as compared with high temperature at 30 ​°C, low-temperature at 22 ​°C affects less on osgmybl2 fertility. Collectively, we proposed that OsGAMYBL2 is likely involved in the regulation of starch accumulation during later pollen development with a thermal-sensitive way, which improves our understanding on the reproductive development in plants.

With the increasing interest in autonomous transport, machine vision and remote sensing, several three-dimensional time-of-flight (ToF) imaging technologies that can recover object's fine details have been presented. Single-pixel imaging provides an alternative to ToF photon-counting imaging with a scanned laser spot. In this work, we present a pseudo-random spread spectrum technique based single-pixel ToF imaging method, which can avoid the range ambiguity, broaden the range of signal frequencies. In addition, the Quadratic Correlation Reconstruction algorithm is applied to further increase the accuracy. With environmental light and system noise, compared to the conventional ToF single-pixel lidar we demonstrate that this approach enhances scene reconstruction quality with depth accuracy improvements of 10.5. This method may open a new gate for improved non-scanning lidar systems.

Abstract Formins are actin-binding proteins that are key to maintaining the actin cytoskeleton in cells. However, molecular mechanisms controlling the stability of formin proteins in plants remain unknown. Here, we have identified six rice SIAH-type E3 ligases, named RIP1-6 (RMD Interacting Protein 1–6) respectively, with ubiquitination enzyme activity in vitro. All six proteins can form homo- and hetero-dimers with themselves, and hetero-dimers with type II formin RMD/OsFH5. In vivo assays showed that RIP1-6 proteins localize in the cytoplasm with a punctate distribution, and all of them interact with RMD to change its native diffuse cytoplasmic localization to match that of RIP1-6. To our surprise, degradation experiments revealed that RIP1, RIP5, and RIP6 decrease rather than increase the degradation rate of RMD. Genetic analyses revealed redundancy between these six genes; either single or double mutants did not show any obvious phenotypes. However, the sextuple rip1-6 mutant displayed dwarf height, wrinkled seeds and wider leaves that were similar to the previously reported rmd mutant, and defective microfilaments and increased flag leaf angles that were not reported in rmd mutant. Collectively, our study provides insights into the mechanisms determining formin protein stability in plants.

Abstract Background To initiate fecal and oral collections in prospective cohort studies for microbial analyses, it is essential to understand how field conditions and geographic differences may impact microbial communities. This study aimed to investigate the impact of fecal and oral sample collection methods and room temperature storage on collection samples for studies of the human microbiota. Results We collected fecal and oral samples from participants in two Iranian cohorts located in rural Yazd (n = 46) and urban Gonbad (n = 38) and investigated room temperature stability over 4 days of fecal (RNAlater and fecal occult blood test [FOBT] cards) and comparability of fecal and oral (OMNIgene ORAL kits and Scope mouthwash) collection methods. We calculated interclass correlation coefficients (ICCs) based on 3 alpha and 4 beta diversity metrics and the relative abundance of 3 phyla. After 4 days at room temperature, fecal stability ICCs and ICCs for Scope mouthwash were generally high for all microbial metrics. Similarly, the fecal comparability ICCs for RNAlater and FOBT cards were high, ranging from 0.63 (95% CI: 0.46, 0.75) for the relative abundance of Firmicutes to 0.93 (95% CI: 0.89, 0.96) for unweighted Unifrac. Comparability ICCs for OMNIgene ORAL and Scope mouthwash were lower than fecal ICCs, ranging from 0.55 (95% CI: 0.36, 0.70) for the Shannon index to 0.79 (95% CI: 0.69, 0.86) for Bray-Curtis. Overall, RNAlater, FOBT cards and Scope mouthwash were stable up to 4 days at room temperature. Samples collected using FOBT cards were generally comparable to RNAlater while the OMNIgene ORAL were less similar to Scope mouthwash. Conclusions As microbiome measures for feces samples collected using RNAlater, FOBT cards and oral samples collected using Scope mouthwash were stable over four days at room temperature, these would be most appropriate for microbial analyses in these populations. However, one collection method should be consistently since each method may induce some differences.

Here we describe an uncommon case of a 48-year-old male patient with an invasive thymoma invading the superior vena cava, bilateral innominate veins, right internal jugular vein, right subclavian vein, right atrium, azygos vein, and part of the lung tissues. The tumor was resected entirely under cardiopulmonary bypass support, and the venous bypass using a vascular graft was successfully established between the left innominate vein and the right atrium. The postoperative course was uneventful, and the patient was discharged 15 days after surgery without complications.

Abstract γ‐oryzanol is the most studied component in rice (Oryza sativa L.) bran oil. It is not only associated with physiological processes of rice growth and development but also grain quality that is related to human health. Previous studies focused mainly on γ‐oryzanol composition and content in various rice cultivars, while its biosynthetic and regulatory pathways remain unknown. Here we present the quantitative identification of γ‐oryzanol in rice seeds across 179 Asian cultivated accessions using ultra‐performance liquid chromatography–time‐of‐flight mass spectrometry (UPLC‐TOF/MS), which revealed a significant natural variation in γ‐oryzanol content among these tested rice accessions. In addition, we present, for the first time, the genome‐wide association study (GWAS) on rice seed γ‐oryzanol, which identified 187 GWAS signal hot spots and 13 candidate genes that are associated with variable γ‐oryzanol content and provided the top 10 rice haplotypes with high γ‐oryzanol content for breeding. Collectively, our study provides valuable germplasms for breeding rice cultivars rich in γ‐oryzanol and genetic resources for elucidating genetic and biochemical bases of variable γ‐oryzanol in rice.

The vacuole is an important organelle with multiple functions in plants, and the tonoplast that wraps the vacuole also plays essential roles in intracellular trafficking and ion homeostasis. Previous studies found that tonoplast proton pumps regulate embryo development and morphogenesis through their effects on vacuole biogenesis and distribution, as well as polar auxin transport and concomitant auxin gradient. However, the precise roles of the tonoplast proton pumps in gametophyte development remain unclear. Here we demonstrated that the lack of two types of tonoplast proton pumps or the absence of V-ATPase alone leads to abnormal development and nuclear localization of female gametophyte (FG), and slowed endosperm nuclei division after fertilization of the central cell. We further revealed that V-ATPase regulates auxin levels in ovules through coordinating the content and localization of PIN-FORMED 1 (PIN1) protein, hence influencing nuclear spacing between centra cell and egg cell, and subsequent endosperm development. Collectively, our findings revealed a crucial role of V-ATPase in auxin-mediated FG development in Arabidopsis and expanded our understanding of the functions of tonoplast proton pumps in seed plants reproductive development.

Spontaneous bursts in neuronal networks with propagation involving a large number of synchronously firing neurons are considered to be a crucial feature of these networks both in vivo and in vitro. Recently, learning has been shown to improve the association and synchronization of spontaneous events in neuronal networks by promoting the firing of spontaneous bursts. However, little is known about the relationship between the learning phase and spontaneous bursts. By combining high-resolution measurement with a 4,096-channel complementary metal-oxide-semiconductor (CMOS) microelectrode array (MEA) and graph theory, we studied how the learning phase influenced the initiation of spontaneous bursts in cultured networks of rat cortical neurons in vitro. We found that a small number of selected populations carried most of the stimulus information and contributed to learning. Moreover, several new burst propagation patterns appeared in spontaneous firing after learning. Importantly, these “learning populations” had more hubs in the functional network that governed the initiation of spontaneous burst activity. These results suggest that changes in the functional structure of learning populations may be the key mechanism underlying increased bursts after learning. Our findings could increase understanding of the important role that synaptic plasticity plays in the regulation of spontaneous activity.

Skull base chordomas are treated with surgery and chemotherapy but often recur due to incomplete resection, understanding the molecular underpinnings of the tumours may provide additional therapeutic strategies. Here, the authors carry out whole genome sequencing of 80 skull base chordoma tumours and identify the SWI/SNF component—PBRM1—as a frequently mutated gene.

Low temperature germination (LTG) is a key agronomic trait in rice (Oryza sativa L.). However, the genetic basis of natural variation for LTG is largely unknown. Here, a genome-wide association study (GWAS) was performed using 276 accessions from the 3,000 Rice Genomes (3K-RG) project with 497 k single nucleotide polymorphisms (SNPs) to uncover potential genes for LTG in rice. In total, 37 quantitative trait loci (QTLs) from the 6th day (D6) to the 10th day (D10) were detected in the full population, overlapping with 12 previously reported QTLs for LTG. One novel QTL, namely qLTG1-2, was found stably on D7 in both 2019 and 2020. Based on two germination-specific transcriptome datasets, 13 seed-expressed genes were isolated within a 200 kb interval of qLTG1-2. Combining with haplotype analysis, a functional uncharacterized gene, LOC_Os01g23580, and a seed germination-associated gene, LOC_Os01g23620 (OsSar1a), as promising candidate genes, both of which were significantly differentially expressed between high and low LTG accessions. Collectively, the candidate genes with favorable alleles may be useful for the future characterization of the LTG mechanism and the improvement of the LTG trait in rice breeding.

Abstract Background For patients with acute exacerbation of COPD (AECOPD), type 2 diabetes mellitus (T2DM) as comorbidity have poor outcomes. However, data on the impact of previously diagnosed and new- diagnosed T2DM in such a patient population is lacking. Methods Inpatients diagnosed with AECOPD in the department of Pulmonary and Critical Care Medicine of The First Hospital of China Medical University during 2011–2017 were enrolled. Data on demography, prevalence of type 2 DM, other comorbidities, hospital stays and laboratory tests (including arterial partial pressure of oxygen [PaO2]) results were recorded. Results were compared with AECOPD patients having previously diagnosed and new-diagnosed type 2 diabetes. Markers associated with development of type 2 DM and the prognosis of AECOPD patients were identified. Results Of the 196 patients enrolled in this study, the overall prevalence of T2DM was 26%. The PaO2 in the newly diagnosed T2DM group was considerably lower versus non-diabetic group. The T2DM group had a longer hospital stay and higher troponin level versus the non-diabetic group. AECOPD patients with T2DM were found to be correlated with hypertension. Age, need for assisted ventilation, increased troponin, and elevated fasting blood glucose on admission were risk factors for death in hospitalized AECOPD patients. Conclusions AECOPD patients had a higher prevalence of T2DM than the general population; T2DM comorbidity caused lower PaO2, longer hospital stays, and increased troponin. Poor blood glucose control may increase the risk of death in AECOPD patients.

Many tumours are heterogenous, which calls into question whether multiple biopsies are required to accurately assess the cancer. Here, the authors show that papillary renal cell carcinoma is clonal in nature, suggesting that in this cancer one biopsy is sufficient for diagnosis and molecular analyses.

Many tumors are known to be heterogeneous. Here, the authors examined multiple samples from 84 patients with lung adenocarcinoma and demonstrate that the intratumor heterogeneity of methylation and copy number associates with poor prognosis.