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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.

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.

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.

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.

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.

Sheep horns are composed of bone and sheaths, and the BMPR1A gene is required for cartilage and osteogenic differentiation. Therefore, the BMPR1A gene may have a function related to the sheep horn, but its relationship with the sheep horn remains unclear. In this study, we first utilized RNA sequencing (RNA-seq) data to investigate the expression of the BMPR1A gene in different tissues and breeds of sheep. Second, whole-genome sequencing (WGS) data were used to explore the functional sites of the BMPR1A gene. Lastly, the allele-specific expression of the BMPR1A gene was explored. Our results indicate that BMPR1A gene expression is significantly higher in the normal horn groups than in the scurred groups. Importantly, this trend is consistent across several sheep breeds. Therefore, this finding suggests that the BMPR1A gene may be related to horn type. A total of 43 Single-Nucleotide Polymorphisms (SNPs) (F-statistics > 0.15) and 10 allele-specific expressions (ASEs) exhibited difference between the large and small horn populations. It is probable that these sites significantly impact the size of sheep horns. Compared to other polled species, we discovered ten amino acid sites that could influence horn presence. By combining RNA-seq and WGS functional loci results, we identified a functional site at position 40574836 on chromosome 25 that is both an SNP and exhibits allele-specific expression. In conclusion, we demonstrated that the BMPR1A gene is associated with horn type and identified some important functional sites which can be used as molecular markers in the breeding of sheep horns.

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.

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.

For de novo mutational signature analysis, the critical first step is to decide how many signatures should be expected in a cancer genomics study. An incorrect number could mislead downstream analyses. Here we present SUITOR (Selecting the nUmber of mutatIonal signaTures thrOugh cRoss-validation), an unsupervised cross-validation method that requires little assumptions and no numerical approximations to select the optimal number of signatures without overfitting the data. In vitro studies and in silico simulations demonstrated that SUITOR can correctly identify signatures, some of which were missed by other widely used methods. Applied to 2,540 whole-genome sequenced tumors across 22 cancer types, SUITOR selected signatures with the smallest prediction errors and almost all signatures of breast cancer selected by SUITOR were validated in an independent breast cancer study. SUITOR is a powerful tool to select the optimal number of mutational signatures, facilitating downstream analyses with etiological or therapeutic importance.

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.

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.

Summary: Recent genomic studies suggest that Asian breast cancer (BC) may have distinct somatic features; however, most comparisons of BC genomic features across populations did not account for differences in age, subtype, and sequencing methods. In this study, we analyzed whole-exome sequencing (WES) data to characterize somatic copy number alterations (SCNAs) and mutation profiles in 98 Hong Kong BC (HKBC) patients and compared with those from The Cancer Genome Atlas of European ancestry (TCGA-EA, N = 686), which had similar distributions of age at diagnosis and PAM50 subtypes as in HKBC. We developed a two-sample Poisson model to compare driver gene selection pressure, which reflects the effect sizes of cancer driver genes, while accounting for differences in sample size, sequencing platforms, depths, and mutation calling methods. We found that somatic mutation and SCNA profiles were overall very similar between HKBC and TCGA-EA. The selection pressure for small insertions and deletions (indels) in GATA3 (false discovery rate (FDR) corrected p < 0.01) and single-nucleotide variants (SNVs) in TP53 (nominal p = 0.02, FDR corrected p = 0.28) was lower in HKBC than in TCGA-EA. Among the 13 signatures of single-base substitutions (SBS) that are common in BC, we found a suggestively higher contribution of SBS18 and a lower contribution of SBS1 in HKBC than in TCGA-EA, while the two APOBEC-induced signatures showed similar prevalence. Our results suggest that the genomic landscape of BC was largely very similar between HKBC and TCGA-EA, despite suggestive differences in some driver genes and mutational signatures that warrant future investigations in large and diverse Asian populations.

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.

Abstract Background Oral microbiota may be related to pancreatic cancer risk because periodontal disease, a condition linked to multiple specific microbes, has been associated with increased risk of pancreatic cancer. We evaluated the association between oral microbiota and pancreatic cancer in Iran. Methods A total of 273 pancreatic adenocarcinoma cases and 285 controls recruited from tertiary hospitals and a specialty clinic in Tehran, Iran provided saliva samples and filled out a questionnaire regarding demographics and lifestyle characteristics. DNA was extracted from saliva and the V4 region of the 16S rRNA gene was PCR amplified and sequenced on the MiSeq. The sequencing data were processed using the DADA2 plugin in QIIME 2 and taxonomy was assigned against the Human Oral Microbiome Database. Logistic regression and MiRKAT models were calculated with adjustment for potential confounders. Results No association was observed for alpha diversity with an average of 91.11 (standard deviation [SD] 2.59) sequence variants for cases and 89.42 (SD 2.58) for controls. However, there was evidence for an association between beta diversity and case status. The association between the Bray‐Curtis dissimilarity and pancreatic cancer was particularly strong with a MiRKAT P‐value of .000142 and specific principal coordinate vectors had strong associations with cancer risk. Several specific taxa were also associated with case status after adjustment for multiple comparisons. Conclusion The overall microbial community appeared to differ between pancreatic cancer cases and controls. Whether these reflect differences evident before development of pancreatic cancer will need to be evaluated in prospective studies.

Abstract Background Heterogeneity of immune gene expression patterns of luminal breast cancer (BC), which is clinically heterogeneous and overall considered as low immunogenic, has not been well studied especially in non-European populations. Here, we aimed at characterizing the immune gene expression profile of luminal BC in an Asian population and associating it with patient characteristics and tumor genomic features. Methods We performed immune gene expression profiling of tumor and adjacent normal tissue in 92 luminal BC patients from Hong Kong using RNA-sequencing data and used unsupervised consensus clustering to stratify tumors. We then used luminal patients from The Cancer Genome Atlas (TCGA, N = 564) and a Korean breast cancer study (KBC, N = 112) as replication datasets. Results Based on the expression of 130 immune-related genes, luminal tumors were stratified into three distinct immune subtypes. Tumors in one subtype showed higher level of tumor-infiltrating lymphocytes (TILs), characterized by T cell gene activation, higher expression of immune checkpoint genes, higher nonsynonymous mutation burden, and higher APOBEC-signature mutations, compared with other luminal tumors. The high-TIL subtype was also associated with lower ESR1/ESR2 expression ratio and increasing body mass index. The comparison of the immune profile in tumor and matched normal tissue suggested a tumor-derived activation of specific immune responses, which was only seen in high-TIL patients. Tumors in a second subtype were characterized by increased expression of interferon-stimulated genes and enrichment for TP53 somatic mutations. The presence of three immune subtypes within luminal BC was replicated in TCGA and KBC, although the pattern was more similar in Asian populations. The germline APOBEC3B deletion polymorphism, which is prevalent in East Asian populations and was previously linked to immune activation, was not associated with immune subtypes in our study. This result does not support the hypothesis that the germline APOBEC3B deletion polymorphism is the driving force for immune activation in breast tumors in Asian populations. Conclusion Our findings suggest that immune gene expression and associated genomic features could be useful to further stratify luminal BC beyond the current luminal A/B classification and a subset of luminal BC patients may benefit from checkpoint immunotherapy, at least in Asian populations.

Background: The prevalence of insomnia and hypersomnia in depressed individuals is substantially higher than that found in the general population. Unfortunately, these concurrent sleep problems can have profound effects on the disease course. Although the full biology of sleep remains to be elucidated, a recent genome-wide association (GWAS) of insomnia, and other sleep traits in over 1 million individuals was recently published and provides many promising hits for genetics of insomnia in a population-based sample.Methods: Using data from the largest available GWAS of insomnia and other sleep traits, we sought to test if sleep variable PRS scores derived from population-based studies predicted sleep variables in samples of depressed cases [Psychiatric Genomics Consortium - Major Depressive Disorder subjects (PGC MDD)]. A leave-one-out analysis was performed to determine the effects that each individual study had on our results.Results: The only significant finding was for insomnia, where p-value threshold, p = 0.05 was associated with insomnia in our PGC MDD sample (R2 = 1.75−3, p = 0.006).Conclusion: Our results reveal that

The lysozyme-modified nanoparticles (LY@ZnO NPs) were synthesized by the reduction–oxidation method, and the morphology and structure of LY@ZnO were analyzed by Fourier transform infrared (FTIR) spectroscopy, powder X-ray diffraction (XRD), scanning electron microsclope (SEM), and particle size analysis. The antibacterial effects of LY@ZnO against Escherichia coli (E. coli, Gram-negative bacteria) and Staphylococcus aureus (S. aureus, Gram-positive bacteria) were discussed by measuring the zone of inhibition (ZOI) and growth inhibition. The antimicrobial experiments showed that the LY@ZnO NPs possessed better antibacterial activity than ZnO. Besides, the antibacterial mechanism of LY@ZnO was also investigated, which was attributed to the generation of reactive oxygen species (ROS). Furthermore, the toxicities of LY@ZnO in vivo and in vitro were discussed by the cell counting kit-8 method and animal experiments, showing that LY@ZnO possessed excellent biocompatibility. Finally, the therapeutic effect of LY@ZnO on a rat skin infection model caused by methicillin-resistant Staphylococcus aureus (MRSA) was also studied, which exhibited good anti-infective activity. Our findings showed that LY@ZnO possessed remarkable antibacterial ability due to its excellent membrane permeability and small particle size. Besides, LY@ZnO also exhibited certain stability and great safety, which showed tremendous prospects for microbial infection in patients. It would also be helpful for a better understanding of the enzyme-modified nanomaterials against bacteria.

Expression QTL (eQTL) analyses have suggested many genes mediating genome-wide association study (GWAS) signals but most GWAS signals still lack compelling explanatory genes. We have leveraged an adipose-specific gene regulatory network to infer expression regulator activities and phenotypic master regulators (MRs), which were used to detect activity QTLs (aQTLs) at cardiometabolic trait GWAS loci. Regulator activities were inferred with the VIPER algorithm that integrates enrichment of expected expression changes among a regulator's target genes with confidence in their regulator-target network interactions and target overlap between different regulators (i.e., pleiotropy). Phenotypic MRs were identified as those regulators whose activities were most important in predicting their respective phenotypes using random forest modeling. While eQTLs were typically more significant than aQTLs in cis, the opposite was true among candidate MRs in trans. Several GWAS loci colocalized with MR trans-eQTLs/aQTLs in the absence of colocalized cis-QTLs. Intriguingly, at the 1p36.1 BMI GWAS locus the EPHB2 cis-aQTL was stronger than its cis-eQTL and colocalized with the GWAS signal and 35 BMI MR trans-aQTLs, suggesting the GWAS signal may be mediated by effects on EPHB2 activity and its downstream effects on a network of BMI MRs. These MR and aQTL analyses represent systems genetic methods that may be broadly applied to supplement standard eQTL analyses for suggesting molecular effects mediating GWAS signals.

ABSTRACT Cigarettes and opium contain chemicals and particulate matter that may modify the oral microbiota. This study aimed to investigate the association between cigarette and opium use with the oral microbiota. A total of 558 participants were recruited from Iran between 2011 and 2015. Individuals were categorized as never cigarette nor opium users, ever cigarette-only smokers, ever opium-only users, and ever both cigarette and opium users. Participants provided saliva samples for 16S rRNA gene sequencing. Logistic regression, microbiome regression-based kernel association test (MiRKAT), and zero-inflated beta regression models were calculated. For every increase in 10 observed amplicon sequence variants (ASVs), the odds for being a cigarette-only smoker, opium-only user, and both user compared to never users decreased by 9% (odds ratio [OR] = 0.91; 95% confidence interval [95% CI] = 0.86 to 0.97), 13% (OR = 0.87; 95% CI = 0.75 to 1.01), and 12% (OR = 0.88; 95% CI = 0.80 to 0.96), respectively. The microbial communities differed by cigarette and opium use as indicated by MiRKAT models testing the three beta-diversity matrices (P < 0.05 for all). Three genera were less likely and one genus was more likely to be detected in cigarette-only smokers or opium-only users than in never users. The relative abundance of the phylum Actinobacteria (never, 14.78%; both, 21.20%) was higher and the phyla Bacteroidetes (never, 17.63%; both, 11.62%) and Proteobacteria (never, 9.06%; both, 3.70%) were lower in users of both cigarettes and opium, while the phylum Firmicutes (never, 54.29%; opium, 65.49%) was higher in opium-only users. Cigarette and opium use was associated with lower alpha-diversity, overall oral microbiota community composition, and both the presence and relative abundance of multiple taxa. IMPORTANCE Cigarette smoking and opium use are associated with periodontal disease caused by specific bacteria such as Porphyromonas gingivalis, which suggests a link between cigarette smoking and opium use and the oral microbiota. Alterations of the oral microbiota in cigarette smokers compared to nonsmokers have been reported, but this has not been studied across diverse populations. Additionally, the association of opium use with the oral microbiota has not been investigated to date. We conducted this study to investigate differences in the oral microbiota between ever users of cigarettes only, opium only, and both cigarettes and opium and never users of cigarettes and opium in Iran. Lower alpha-diversity, distinct overall oral microbial communities, and the presence and relative abundance of multiple taxa have been found for users of cigarettes and/or opium.

The human microbiome has been recently shown to be associated with disease risks and has important implications in risk stratification and precision medicine. Due to abundant taxa in the human body, microbiome data are high-dimensional and compositional. Dirichlet distributions and their generalization are used to characterize the dependence structures of microbial data. Another existing method for fitting microbiome data employed Gaussian graphical model using the centered log-transformation (CLR). However, Dirichlet distributions are not able to infer networks or to estimate some extremely rare probabilities. On the other hand, it is hard to interpret the network analysis results using CLR. Furthermore, the data analysis showed that there is a lack of efficient multivariate distributions for fitting microbiome data, which results in inadequate statistical inferences. In this paper, we propose new multivariate distributions for modeling the dependence structures of the high dimensional and compositional microbiome data using inverse gamma distributions and copula techniques. The data analysis in the American gut project shows our proposed methods perform well.

Epidemiological studies have observed that risk of endometriosis is associated with history of cutaneous melanoma and vice versa. Evidence for shared biological mechanisms between the two traits is limited. The aim of this study was to investigate the genetic correlation and causal relationship between endometriosis and melanoma. Summary statistics from genome-wide association meta-analyses (GWAS) for endometriosis and melanoma were used to estimate the genetic correlation between the traits and Mendelian randomization was used to test for a causal association. When using summary statistics from separate female and male melanoma cohorts we identified a significant positive genetic correlation between melanoma in females and endometriosis (rg = 0.144, se = 0.065, p = 0.025). However, we find no evidence of a correlation between endometriosis and melanoma in males or a combined melanoma dataset. Endometriosis was not genetically correlated with skin color, red hair, childhood sunburn occasions, ease of skin tanning, or nevus count suggesting that the correlation between endometriosis and melanoma in females is unlikely to be influenced by pigmentary traits. Mendelian Randomization analyses also provided evidence for a relationship between the genetic risk of melanoma in females and endometriosis. Colocalization analysis identified 27 genomic loci jointly associated with the two diseases regions that contain different causal variants influencing each trait independently. This study provides evidence of a small genetic correlation and relationship between the genetic risk of melanoma in females and endometriosis. Genetic risk does not equate to disease occurrence and differences in the pathogenesis and age of onset of both diseases means it is unlikely that occurrence of melanoma causes endometriosis. This study instead provides evidence that having an increased genetic risk for melanoma in females is related to increased risk of endometriosis. Larger GWAS studies with increased power will be required to further investigate these associations.

The microbiome is the collection of all microbial genes and can be investigated by sequencing highly variable regions of 16S ribosomal RNA (rRNA) genes. Evidence suggests that environmental factors and host genetics may interact to impact human microbiome composition. Identifying host genetic variants associated with human microbiome composition not only provides clues for characterizing microbiome variation but also helps to elucidate biological mechanisms of genetic associations, prioritize genetic variants, and improve genetic risk prediction. Since a microbiota functions as a community, it is best characterized by β diversity; that is, a pairwise distance matrix. We develop a statistical framework and a computationally efficient software package, microbiomeGWAS, for identifying host genetic variants associated with microbiome β diversity with or without interacting with an environmental factor. We show that the score statistics have positive skewness and kurtosis due to the dependent nature of the pairwise data, which makes p-value approximations based on asymptotic distributions unacceptably liberal. By correcting for skewness and kurtosis, we develop accurate p-value approximations, whose accuracy was verified by extensive simulations. We exemplify our methods by analyzing a set of 147 genotyped subjects with 16S rRNA microbiome profiles from non-malignant lung tissues. Correcting for skewness and kurtosis eliminated the dramatic deviation in the quantile–quantile plots. We provided preliminary evidence that six established lung cancer risk SNPs were collectively associated with microbiome composition for both unweighted (p = 0.0032) and weighted (p = 0.011) UniFrac distance matrices. In summary, our methods will facilitate analyzing large-scale genome-wide association studies of the human microbiome.

Schima superba (Theaceae) is a subtropical evergreen tree and is used widely for forest firebreaks and gardening. It is a plant that tolerates salt and typically accumulates elevated amounts of manganese in the leaves. With large ecological amplitude, this tree species grows quickly. Due to its substantial biomass, it has a great potential for soil remediation. To evaluate the thorough framework of the mRNA, we employed PacBio sequencing technology for the first time to generate S. Superba transcriptome. In this analysis, overall, 511,759 full length non-chimeric reads were acquired, and 163,834 high-quality full-length reads were obtained. Overall, 93,362 open reading frames were obtained, of which 78,255 were complete. In gene annotation analyses, the Kyoto Encyclopedia of Genes and Genomes (KEGG), Clusters of Orthologous Genes (COG), Gene Ontology (GO), and Non-Redundant (Nr) databases were allocated 91,082, 71,839, 38,914, and 38,376 transcripts, respectively. To identify long non-coding RNAs (lncRNAs), we utilized four computational methods associated with protein families (Pfam), Cooperative Data Classification (CPC), Coding Assessing Potential Tool (CPAT), and Coding Non-Coding Index (CNCI) databases and observed 8,551, 9,174, 20,720, and 18,669 lncRNAs, respectively. Moreover, nine genes were randomly selected for the expression analysis, which showed the highest expression of Gene 6 (Na_Ca_ex gene), and CAX (CAX-interacting protein 4) was higher in manganese (Mn)-treated group. This work provided significant number of full-length transcripts and refined the annotation of the reference genome, which will ease advanced genetic analyses of S. superba.

Abstract Background During pollen wall formation in flowering plants, a conserved metabolon consisting of acyl-CoA synthetase (ACOS), polyketide synthase (PKS) and tetraketide α-pyrone reductase (TKPR), is required for sporopollenin synthesis. Despite this, the precise function of each of these components in different species remains unclear. Results In this study, we characterized the function of OsTKPR1, a rice orthologue of Arabidopsis TKPR1. Loss of function of OsTKPR1 delayed tapetum degradation, reduced the levels of anther cuticular lipids, and impaired Ubisch body and pollen exine formation, resulting in complete male sterility. In addition, the phenylpropanoid pathway in mutant anthers was remarkably altered. Localization studies suggest that OsTKPR1 accumulates in the endoplasmic reticulum, while specific accumulation of OsTKPR1 mRNA in the anther tapetum and microspores is consistent with its function in anther and pollen wall development. Conclusions Our results show that OsTKPR1 is indispensable for anther cuticle development and pollen wall formation in rice, providing new insights into the biochemical mechanisms of the conserved sporopollenin metabolon in flowering plants.

Abstract The National Cancer Institute (NCI) sponsored a 2-day workshop, “Next Steps in Studying the Human Microbiome and Health in Prospective Studies,” in Bethesda, Maryland, May 16–17, 2017. The workshop brought together researchers in the field to discuss the challenges of conducting microbiome studies, including study design, collection and processing of samples, bioinformatics and statistical methods, publishing results, and ensuring reproducibility of published results. The presenters emphasized the great potential of microbiome research in understanding the etiology of cancer. This report summarizes the workshop and presents practical suggestions for conducting microbiome studies, from workshop presenters, moderators, and participants.

We previously identified 10 lung adenocarcinoma susceptibility loci in a genome-wide association study (GWAS) conducted in the Female Lung Cancer Consortium in Asia (FLCCA), the largest genomic study of lung cancer among never-smoking women to date. Furthermore, household coal use for cooking and heating has been linked to lung cancer in Asia, especially in Xuanwei, China. We investigated the potential interaction between genetic susceptibility and coal use in FLCCA. We analyzed GWAS-data from Taiwan, Shanghai, and Shenyang (1472 cases; 1497 controls), as well as a separate study conducted in Xuanwei (152 cases; 522 controls) for additional analyses. We summarized genetic susceptibility using a polygenic risk score (PRS), which was the weighted sum of the risk-alleles from the 10 previously identified loci. We estimated associations between a PRS, coal use (ever/never), and lung adenocarcinoma with multivariable logistic regression models, and evaluated potential gene-environment interactions using likelihood ratio tests. There was a strong association between continuous PRS and lung adenocarcinoma among never coal users (Odds Ratio (OR) = 1.69 (95% Confidence Interval (CI) = 1.53, 1.87), p=1 × 10−26). This effect was attenuated among ever coal users (OR = 1.24 (95% CI: 1.03, 1.50), p = 0.02, p-interaction = 6 × 10−3). We observed similar attenuation among coal users from Xuanwei. Our study provides evidence that genetic susceptibility to lung adenocarcinoma among never-smoking Asian women is weaker among coal users. These results suggest that lung cancer pathogenesis may differ, at least partially, depending on exposure to coal combustion products. Notably, these novel findings are among the few instances of sub-multiplicative gene-environment interactions in the cancer literature.

GDSL esterases/lipases (GELPs), present throughout all living organisms, have been a very attractive research subject in plant science due mainly to constantly emerging properties and functions in plant growth and development under both normal and stressful conditions. This review summarizes the advances in research on plant GELPs in several model plants and crops, including Arabidopsis, rice, maize and tomato, while focusing on the roles of GELPs in regulating plant development and plant–environment interactions. In addition, the possible regulatory network and mechanisms of GELPs have been discussed.