A transformer-based genomic prediction method fused with knowledge-guided module.

Genomic prediction (GP) uses single nucleotide polymorphisms (SNPs) to establish associations between markers and phenotypes. Selection of early individuals by genomic estimated breeding value shortens the generation interval and speeds up the breeding process. Recently, methods based on deep learning (DL) have gained great attention in the field of GP. In this study, we explore the application of Transformer-based structures to GP and develop a novel deep-learning model named GPformer. GPformer obtains a global view by gleaning beneficial information from all relevant SNPs regardless of the physical distance between SNPs. Comprehensive experimental results on five different crop datasets show that GPformer outperforms ridge regression-based linear unbiased prediction (RR-BLUP), support vector regression (SVR), light gradient boosting machine (LightGBM) and deep neural network genomic prediction (DNNGP) in terms of mean absolute error, Pearson's correlation coefficient and the proposed metric consistent index. Furthermore, we introduce a knowledge-guided module (KGM) to extract genome-wide association studies-based information, which is fused into GPformer as prior knowledge. KGM is very flexible and can be plugged into any DL network. Ablation studies of KGM on three datasets illustrate the efficiency of KGM adequately. Moreover, GPformer is robust and stable to hyperparameters and can generalize to each phenotype of every dataset, which is suitable for practical application scenarios.

BTA2 regulates tiller angle and the shoot gravity response through controlling auxin content and distribution in rice.

Tiller angle is a key agricultural trait that establishes plant architecture, which in turn strongly affects grain yield by influencing planting density in rice. The shoot gravity response plays a crucial role in the regulation of tiller angle in rice, but the underlying molecular mechanism is largely unknown. Here, we report the identification of the BIG TILLER ANGLE2 (BTA2), which regulates tiller angle by controlling the shoot gravity response in rice. Loss-of-function mutation of BTA2 dramatically reduced auxin content and affected auxin distribution in rice shoot base, leading to impaired gravitropism and therefore a big tiller angle. BTA2 interacted with AUXIN RESPONSE FACTOR7 (ARF7) to modulate rice tiller angle through the gravity signaling pathway. The BTA2 protein was highly conserved during evolution. Sequence variation in the BTA2 promoter of indica cultivars harboring a less expressed BTA2 allele caused lower BTA2 expression in shoot base and thus wide tiller angle during rice domestication. Overexpression of BTA2 significantly increased grain yield in the elite rice cultivar Huanghuazhan under appropriate dense planting conditions. Our findings thus uncovered the BTA2-ARF7 module that regulates tiller angle by mediating the shoot gravity response. Our work offers a target for genetic manipulation of plant architecture and valuable information for crop improvement by producing the ideal plant type.

Randomized controlled trial of intravesical electrical stimulation for underactive bladder.

AIM: To evaluate the efficacy and safety of intravesical electrical stimulation (IVES) performed with a novel device in patients with underactive bladder (UAB). PATIENTS AND METHODS: This was a multicentre, prospective, single-blind, randomized controlled clinical trial of patients with UAB in China. Eligible patients were randomly assigned in a 1:1 ratio to receive conventional IVES (n = 38) or IVES with an open circuit (n = 38). The primary efficacy measure was change from baseline in post-void residual urine volume (PVR) after 4 weeks of treatment. Secondary efficacy measures included changes in maximum urinary flow rate (Qmax ), bladder voiding efficiency (BVE), number of 24-h clean intermittent catheterization (CIC) procedures, and Patient Perception of Bladder Condition-Scale (PPBC-S) and American Urological Association Symptom Index Quality of Life (AUA-SI-QoL) scores from baseline after 4 weeks of treatment. Adverse events (AEs) were monitored throughout the trial. RESULTS: In the full analysis set (FAS), the mean (sd) PVR changes in the trial and control groups at 4 weeks were -97.1 (107.5) mL and -10.5 (86.7) mL, respectively (P < 0.01). Similar results were obtained in the per-protocol set (PPS): -102.9 (100.0) mL vs 0.7 (82.5) mL (P < 0.01). In the FAS and PPS, Qmax improved significantly at 4 weeks (P = 0.04 and P = 0.03). In the FAS and PPS, BVE was significantly improved at 4 weeks in the two groups (P < 0.01 and P < 0.01), whereas no significant differences in the number of 24-h CIC procedures, PPBC-S score or AUA-SI-QoL score were observed between the groups. Six possible therapy-related AEs occurred in six patients (four in the trial group and two in the control group; P = 0.67), all of which were urinary tract infections. No severe AEs were reported. CONCLUSIONS: The results of this clinical study strongly demonstrate that UAB patients benefit from this novel IVES device. More research is needed to validate the clinical utility of this device.

Integrating genome-wide association study into genomic selection for the prediction of agronomic traits in rice (Oryza sativa L.).

Accurately identifying varieties with targeted agronomic traits was thought to contribute to genetic selection and accelerate rice breeding progress. Genomic selection (GS) is a promising technique that uses markers covering the whole genome to predict the genomic-estimated breeding values (GEBV), with the ability to select before phenotypes are measured. To choose the appropriate GS models for breeding work, we analyzed the predictability of nine agronomic traits measured from a population of 459 diverse rice varieties. By the comparison of eight representative GS models, we found that the prediction accuracies ranged from 0.407 to 0.896, with reproducing kernel Hilbert space (RKHS) having the highest predictive ability in most traits. Further results demonstrated the predictivity of GS is altered by several factors. Moreover, we assessed the method of integrating genome-wide association study (GWAS) into various GS models. The predictabilities of GS combined peak-associated markers generated from six different GWAS models were significantly different; a recommendation of Mixed Linear Model (MLM)-RKHS was given for the GWAS-GS-integrated prediction. Finally, based on the above result, we experimented with applying the P-values obtained from optimal GWAS models into ridge regression best linear unbiased prediction (rrBLUP), which benefited the low predictive traits in rice. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-023-01423-y.

Genomic insight into genetic changes and shaping of major inbred rice cultivars in China.

The annual planting area of major inbred rice (Oryza sativa) cultivars reach more than half of the total annual planting area of inbred rice cultivars in China. However, how the major inbred rice cultivars changed during decades of genetic improvement and why they can be prevalently cultivated in China remains unclear. Here, we investigated the underlying genetic changes of major inbred cultivars and the contributions of landraces and introduced cultivars during the improvement by resequencing a collection of 439 rice accessions including major inbred cultivars, landraces, and introduced cultivars. The results showed that landraces were the main genetic contribution sources of major inbred Xian (Indica) cultivars, while introduced cultivars were that of major inbred Geng (Japonica) cultivars. Selection scans and haplotype frequency analysis shed light on the reflections of some well-known genes in rice improvement, and breeders had different preferences for the Xian's and Geng's breeding. Six candidate regions associated with agronomic traits were identified by genome-wide association mapping, five of which were under positive selection in rice improvement. Our study provides a comprehensive insight into the development of major inbred rice cultivars and lays the foundation for genomics-based breeding in rice.

Parallel Speciation of Wild Rice Associated with Habitat Shifts.

The occurrence of parallel speciation strongly implies the action of natural selection. However, it is unclear how general a phenomena parallel speciation is since it was only shown in a small number of animal species. In particular, the adaptive process and mechanisms underlying the process of parallel speciation remain elusive. Here, we used an integrative approach incorporating population genomics, common garden, and crossing experiments to investigate parallel speciation of the wild rice species Oryza nivara from O. rufipogon. We demonstrated that O. nivara originated multiple times from different O. rufipogon populations and revealed that different O. nivara populations have evolved similar phenotypes under divergent selection, a reflection of recurrent local adaptation of ancient O. rufipogon populations to dry habitats. Almost completed premating isolation was detected between O. nivara and O. rufipogon in the absence of any postmating barriers between and within these species. These results suggest that flowering time is a "magic" trait that contributes to both local adaptation and reproductive isolation in the origin of wild rice species. Our study thus demonstrates a convincing case of parallel ecological speciation as a consequence of adaptation to new environments.

A map of rice genome variation reveals the origin of cultivated rice.

Crop domestications are long-term selection experiments that have greatly advanced human civilization. The domestication of cultivated rice (Oryza sativa L.) ranks as one of the most important developments in history. However, its origins and domestication processes are controversial and have long been debated. Here we generate genome sequences from 446 geographically diverse accessions of the wild rice species Oryza rufipogon, the immediate ancestral progenitor of cultivated rice, and from 1,083 cultivated indica and japonica varieties to construct a comprehensive map of rice genome variation. In the search for signatures of selection, we identify 55 selective sweeps that have occurred during domestication. In-depth analyses of the domestication sweeps and genome-wide patterns reveal that Oryza sativa japonica rice was first domesticated from a specific population of O. rufipogon around the middle area of the Pearl River in southern China, and that Oryza sativa indica rice was subsequently developed from crosses between japonica rice and local wild rice as the initial cultivars spread into South East and South Asia. The domestication-associated traits are analysed through high-resolution genetic mapping. This study provides an important resource for rice breeding and an effective genomics approach for crop domestication research.

Genome-wide association study of cold tolerance of Chinese indica rice varieties at the bud burst stage.

KEY MESSAGE: A region containing three genes on chromosome 1 of indica rice was associated with cold tolerance at the bud burst stage; these results may be useful for breeding cold-tolerant lines. Low temperature at the bud burst stage is one of the major abiotic stresses limiting rice growth, especially in regions where rice seeds are sown directly. In this study, we investigated cold tolerance of rice at the bud burst stage and conducted a genome-wide association study (GWAS) based on the 5K rice array of 249 indica rice varieties widely distributed in China. We improved the method to assess cold tolerance at the bud burst stage in indica rice, and used severity of damage (SD) and seed survival rate (SR) as the cold-tolerant indices. Population structure analysis demonstrated that the Chinese indica panel was divided into three subgroups. In total, 47 significant single-nucleotide polymorphism (SNP) loci associated with SD and SR, were detected by association mapping based on mixed linear model. Because some loci overlapped between SD and SR, the loci contained 13 genome intervals and most of them have been reported previously. A major QTL for cold tolerance on chromosome 1 at the position of 31.6 Mb, explaining 13.2% of phenotypic variation, was selected for further analysis. Through LD decay, GO enrichment, RNA-seq data, and gene expression pattern analyses, we identified three genes (LOC_Os01g55510, LOC_Os01g55350 and LOC_Os01g55560) that were differentially expressed between cold-tolerant and cold-sensitive varieties, suggesting they may be candidate genes for cold tolerance. Together, our results provide a new method to assess cold tolerance in indica rice, and establish the foundation for isolating genes related to cold tolerance that could be used in rice breeding.

Comparative Proteomic Analysis of Rana chensinensis Oviduct.

As one of most important traditional Chinese medicine resources, the oviduct of female Rana chensinensis (Chinese brown frog) was widely used in the treatment of asthenia after sickness or delivery, deficiency in vigor, palpitation, and insomnia. Unlike other vertebrates, the oviduct of Rana chensinensis oviduct significantly expands during prehibernation, in contrast to the breeding period. To explain this phenomenon at the molecular level, the protein expression profiles of Rana chensinensis oviduct during the breeding period and prehibernation were observed using isobaric tags for relative and absolute quantitation (iTRAQ) technique. Then, all identified proteins were used to obtain gene ontology (GO) annotation. Ultimately, KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis was performed to predict the pathway on differentially expressed proteins (DEPs). A total of 4479 proteins were identified, and 312 of them presented different expression profiling between prehibernation and breeding period. Compared with prehibernation group, 86 proteins were upregulated, and 226 proteins were downregulated in breeding period. After KEGG enrichment analysis, 163 DEPs were involved in 6 pathways, which were lysosome, RNA transport, glycosaminoglycan degradation, extracellular matrix (ECM)⁻receptor interaction, metabolic pathways and focal adhesion. This is the first report on the protein profiling of Rana chensinensis oviduct during the breeding period and prehibernation. Results show that this distinctive physiological phenomenon of Rana chensinensis oviduct was mainly involved in ECM⁻receptor interaction, metabolic pathways, and focal adhesion.

Widespread and Adaptive Alterations in Genome-Wide Gene Expression Associated with Ecological Divergence of Two Oryza Species.

Ecological speciation is a common mechanism by which new species arise. Despite great efforts, the role of gene expression in ecological divergence and speciation is poorly understood. Here, we conducted a genome-wide gene expression investigation of two Oryza species that are evolutionarily young and distinct in ecology and morphology. Using digital gene expression technology and the paired-end RNA sequencing method, we obtained 21,415 expressed genes across three reproduction-related tissues. Of them, approximately 8% (1,717) differed significantly in expression levels between the two species and these differentially expressed genes are randomly distributed across the genome. Moreover, 62% (1,064) of the differentially expressed genes exhibited a signature of directional selection in at least one species. Importantly, the genes with differential expression between species evolved more rapidly at the 5' flanking sequences than the genes without differential expression relative to coding sequences, suggesting that cis-regulatory changes are likely adaptive and play an important role in the ecological divergence of the two species. Finally, we showed evidence of significant differentiation between species in phenotype traits and observed that genes with differential expression were overrepresented with functional terms involving phenotypic and ecological differentiation between the two species, including reproduction- and stress-related characteristics. Our findings demonstrate that ecological speciation is associated with widespread and adaptive alterations in genome-wide gene expression and provide new insights into the importance of regulatory evolution in ecological speciation in plants.

Uncovering novel loci for mesocotyl elongation and shoot length in indica rice through genome-wide association mapping.

MAIN CONCLUSION: Totally, 23 loci were detected, and 383 candidate genes were identified, and four of these candidate genes, Os01g0392100, Os04g0630000, Os01g0904700 and Os07g0615000, were regarded as promising targets. Direct-seeding cultivation is becoming popular in rice (Oryza sativa L.)-planting countries because it is labor- and time-efficient. However, low seedling establishment and slow seedling emergence have restricted the application and popularity of the technique. Mesocotyl elongation and shoot length are two important traits that can enhance rice seedling emergence. A single nucleotide polymorphism (SNP) is a genome sequence variation caused by a single base within a population, and SNPs evenly distributed throughout the genomes of plant species. In this study, a genome-wide association study (GWAS), based on 4136 SNPs, was performed using a compressed mixed linear model that accounted for population structure and relative kinship to detect novel loci for the two traits. Totally, 23 loci were identified, including five loci located known QTLs region. For the mesocotyl elongation, 17 major loci were identified, explaining ~19.31 % of the phenotypic variation. For the shoot length, six major loci were detected, explaining ~ 39.79 % of the phenotypic variation. In total, 383 candidate genes were included in a 200-kb genomic region (± 100 kb of each locus). Additionally, 32 SNPs were identified in 30 candidate genes. Relative expression level analyses indicated that four candidate genes containing SNP variations, Os01g0392100, Os04g0630000, Os01g0904700 and Os07g0615000, represented promising targets. Finally, eight elite accessions with long mesocotyl and shoot lengths were chosen as breeding donors for further rice direct-seeding variety modifications.

Genome wide association mapping for grain shape traits in indica rice.

MAIN CONCLUSION: Using genome-wide association mapping, 47 SNPs within 27 significant loci were identified for four grain shape traits, and 424 candidate genes were predicted from public database. Grain shape is a key determinant of grain yield and quality in rice (Oryza sativa L.). However, our knowledge of genes controlling rice grain shape remains limited. Genome-wide association mapping based on linkage disequilibrium (LD) has recently emerged as an effective approach for identifying genes or quantitative trait loci (QTL) underlying complex traits in plants. In this study, association mapping based on 5291 single nucleotide polymorphisms (SNPs) was conducted to identify significant loci associated with grain shape traits in a global collection of 469 diverse rice accessions. A total of 47 SNPs were located in 27 significant loci for four grain traits, and explained ~44.93-65.90 % of the phenotypic variation for each trait. In total, 424 candidate genes within a 200 kb extension region (±100 kb of each locus) of these loci were predicted. Of them, the cloned genes GS3 and qSW5 showed very strong effects on grain length and grain width in our study. Comparing with previously reported QTLs for grain shape traits, we found 11 novel loci, including 3, 3, 2 and 3 loci for grain length, grain width, grain length-width ratio and thousand grain weight, respectively. Validation of these new loci would be performed in the future studies. These results revealed that besides GS3 and qSW5, multiple novel loci and mechanisms were involved in determining rice grain shape. These findings provided valuable information for understanding of the genetic control of grain shape and molecular marker assistant selection (MAS) breeding in rice.

The genetic diversity and structure of indica rice in China as detected by single nucleotide polymorphism analysis.

BACKGROUND: Rice (Oryza sativa L.) is the staple food of more than half of the world's population. The identification of genetic diversity in local varieties of rice compared with that of improved or introduced varieties is important in breeding elite varieties for sustainable agriculture. Array-based single nucleotide polymorphism (SNP) detection is a useful technique for such studies and breeding applications. RESULTS: We developed a 5291-SNP genome-wide array and used it to genotype 471 indica rice accessions in China using Illumina's Infinium technology. Local, introduced, and improved rice varieties were clustered into three sub-groups, with some overlapping shown in principal component analysis and neighbor-joining tree, also confirmed by model-based structure. A minor allele frequency ≥ 0.2 was observed in 72% of polymorphic SNPs in local rice varieties, which was higher than that in other sub-groups. Local rice varieties also had the highest mean polymorphism information content (PIC) and genetic diversity. Analysis of molecular variance showed that 90.61% of genetic variation was a result of differences within sub-groups. CONCLUSIONS: Our results revealed that SNP analysis clustered local varieties, introduced varieties, and improved varieties into three clear sub-groups. The distribution of parameter PIC values on sub-group genomes revealed that genetic differentiation among them might not be on a genome-wide scale, but rather on selected loci or chromosomal intervals. The result of Gene Ontology enrichment analysis showed that genes nearby those selected SNPs associated different molecular functions or various traits among sub-groups.

Genetic variation and association mapping for 12 agronomic traits in indica rice.

BACKGROUND: Increasing rice (Oryza sativa L.) yield is a crucial challenge for modern agriculture. The ideal plant architecture is considered to be critical to enhance rice yield. Elite plant morphological traits should include compact plant type, short stature, few unproductive tillers, thick and sturdy stems and erect leaves. To reveal the genetic variations of important morphological traits, 523 germplasm accessions were genotyped using the Illumina custom-designed array containing 5,291 single nucleotide polymorphisms (SNPs) and phenotyped in two independent environments. Genome-wide association studies were performed to uncover the genotypic and phenotypic variations using a mixed linear model. RESULTS: In total, 126 and 172 significant loci were identified and these loci explained an average of 34.45% and 39.09% of the phenotypic variance in two environments, respectively, and 16 of 298 (~5.37%) loci were detected across the two environments. For the 16 loci, 423 candidate genes were predicted in a 200-kb region (±100 kb of the peak SNP). Expression-level analyses identified four candidate genes as the most promising regulators of tiller angle. Known (NAL1 and Rc) and new significant loci showed pleiotropy and gene linkage. In addition, a long genome region covering ~1.6 Mb on chromosome 11 was identified, which may be critical for rice leaf architecture because of a high association with flag leaf length and the ratio of flag leaf length and width. The pyramid effect of the elite alleles indicated that these significant loci could be beneficial for rice plant architecture improvements in the future. Finally, 37 elite varieties were chosen as breeding donors for further rice plant architectural modifications. CONCLUSIONS: This study detected multiple novel loci and candidate genes related to rice morphological traits, and the work demonstrated that genome-wide association studies are powerful strategies for uncovering the genetic variations of complex traits and identifying candidate genes in rice, even though the linkage disequilibrium decayed slowly in self-pollinating species. Future research will focus on the biological validation of the candidate genes, and elite varieties will also be of interest in genome selection and breeding by design.

Plasma proteasomal chymotrypsin-like activity correlates with prostate cancer progression.

Previously, we demonstrated that inhibition of proteasomal chymotrypsin-like (CT-like) activity in human prostate cancer (PCa) PC-3 cultures and PC-3 xenografts results in accumulation of ubiquitinated proteins, followed by induction of cell death. Studies have shown that plasma CT-like proteasomal activity may be a powerful biomarker for risk stratification in hematologic malignancies. We hypothesized that circulating proteasomes could also be used to stratify risk for patients with PCa. A total of 109 patients with suspected PCa underwent prostatic biopsies were enrolled. Subjects were divided into non-cancer, low-risk PCa, and high-risk PCa groups. Three different proteasomal activity markers (CT-like, caspase-like, and trypsin-like) were measured and compared among the three groups. The proteasomal target proteins, Ub-prs, Hsp70, Bax, and P27 in plasma and prostate tissues were also evaluated. Multivariate analysis was used to assess whether CT-like activity was a predictor of PCa progression. Only proteasomal CT-like activity in the high-risk group was statistically higher than in the non-cancer group (P < 0.05). The expression of Ub-prs, Hsp70, Bax, and P27 protein was decreased in both plasma and PCa tissue of high-risk patients. CT-like activity was found to be an independent predictor of high-risk PCa. Subjects with CT-like activity ≥55 had a 2.15-fold higher risk of having high-risk PCa as compared to those with a CT-like activity of <55 (P = 0.021). We found CT-like activity to be an independent predictor of high-risk PCa, and as such, it may be a good candidate as a biomarker for high-risk PCa detection and stratification.

Genome-wide association study of blast resistance in indica rice.

BACKGROUND: Rice blast disease is one of the most serious and recurrent problems in rice-growing regions worldwide. Most resistance genes were identified by linkage mapping using genetic populations. We extensively examined 16 rice blast strains and a further genome-wide association study based on genotyping 0.8 million single nucleotide polymorphism variants across 366 diverse indica accessions. RESULTS: Totally, thirty associated loci were identified. The strongest signal (Chr11_6526998, P =1.17 × 10-17) was located within the gene Os11g0225100, one of the rice Pia-blast resistance gene. Another association signal (Chr11_30606558) was detected around the QTL Pif. Our study identified the gene Os11g0704100, a disease resistance protein containing nucleotide binding site-leucine rich repeat domain, as the main candidate gene of Pif. In order to explore the potential mechanism underlying the blast resistance, we further examined a locus in chromosome 12, which was associated with CH149 (P =7.53 × 10-15). The genes, Os12g0424700 and Os12g0427000, both described as kinase-like domain containing protein, were presumed to be required for the full function of this locus. Furthermore, we found some association on chromosome 3, in which it has not been reported any loci associated with rice blast resistance. In addition, we identified novel functional candidate genes, which might participate in the resistance regulation. CONCLUSIONS: This work provides the basis of further study of the potential function of these candidate genes. A subset of true associations would be weakly associated with outcome in any given GWAS; therefore, large-scale replication is necessary to confirm our results. Future research will focus on validating the effects of these candidate genes and their functional variants using genetic transformation and transferred DNA insertion mutant screens, to verify that these genes engender resistance to blast disease in rice.

MLN2238 synergizes BH3 mimetic ABT-263 in castration-resistant prostate cancer cells by induction of NOXA.

Patients undergoing androgen blockade therapy develop castration-resistant prostate cancer (CRPC), which is associated with Bcl-2 upregulation and results in disease progression and death. In recent years, promising therapeutic agents, such as the BH3-only mimetic ABT-263 and proteasome inhibitors, have been developed and widely evaluated against a broad spectrum of cancer types, including prostate cancer, alone or in combination with other chemotherapeutic agents. In this study, the antitumor efficacy of ABT-263 and MLN2238 were evaluated as single agents and in combination in four CRPC cell lines: PC3, C4-2B, C4-2, and DU145. The viability of the treated cells and markers of apoptosis were assayed. Protein-protein interactions were analyzed by co-immunoprecipitation in drug-treated cells. Lentivirus-mediated short hairpin RNA was used to knockdown Bax, Mcl-1, and NOXA expressions. We found that ABT-263 and MLN2238 alone exhibited a mild cytotoxicity, and in combination, they elicited a synergistic cytotoxic effect in CRPC cells. The cell apoptosis induced by the combination drug treatment was evidenced by enhanced caspase-3 and Poly (ADP-ribose) polymerase (PARP) cleavage, and annexin-V-positive staining was significantly depleted by Bax knockdown. MLN2238 treatment upregulated NOXA and Mcl-1 expression, leading NOXA/Mcl-1 complexes to disassociate Bak from its complexes with Mcl-1 and enhancing ABT263-triggered Bax activation. NOXA knockdown by short hairpin RNA significantly attenuated the cytotoxicity of ABT-263 and MLN2238 co-administration. In conclusion, MLN2238 and ABT-263 synergistically triggered apoptosis in CRPC cells by upregulating NOXA and activating Bax, indicating a promising therapeutic strategy for the treatment of CRPC.

Population genomic analysis unravels the evolutionary roadmap of pericarp color in rice.

Pigmented rice stands out for its nutritional value and is gaining more and more attention. Wild rice, domesticated red rice, and weedy rice all have a red pericarp and a comprehensive genetic background in terms of the red-pericarp phenotype. We performed population genetic analyses using 5104 worldwide rice accessions, including 2794 accessions with red or black pericarps, 85 of which were newly sequenced in this study. The results suggested an evolutionary trajectory of red landraces originating from wild rice, and the split times of cultivated red and white rice populations were estimated to be within the past 3500 years. Cultivated red rice was found to feralize to weedy rice, and weedy rice could be further re-domesticated to cultivated red rice. A genome-wide association study based on the 2794 accessions with pigmented pericarps revealed several new candidate genes associated with the red-pericarp trait for further functional characterization. Our results provide genomic evidence for the origin of pigmented rice and a valuable genomic resource for genetic investigation and breeding of pigmented rice.

Three-dimensional gait analysis of orthopaedic common foot and ankle joint diseases.

Walking is an indispensable mode of transportation for human survival. Gait is a characteristic of walking. In the clinic, patients with different diseases exhibit different gait characteristics. Gait analysis describes the specific situation of human gait abnormalities by observing and studying the kinematics and dynamics of limbs and joints during human walking and depicting the corresponding geometric curves and values. In foot and ankle diseases, gait analysis can evaluate the degree and nature of gait abnormalities in patients and provide an important basis for the diagnosis of patients' diseases, the correction of abnormal gait and related treatment methods. This article reviews the relevant literature, expounds on the clinical consensus on gait, and summarizes the gait characteristics of patients with common ankle and foot diseases. Starting from the gait characteristics of individuals with different diseases, we hope to provide support and reference for the diagnosis, treatment and rehabilitation of clinically related diseases.

A KNOX â ¡ transcription factor suppresses the NLR immune receptor BRG8-mediated immunity in rice.

Nucleotide-binding site and leucine-rich repeat (NLR) proteins are activated by detecting pathogen effectors, which in turn trigger host defenses and cell death. Although many NLRs have been identified, the mechanism responsible for NLR-triggered defense responses are still poorly understood. In this study, through GWAS approach, we identified a novel NLR gene, Blast Resistance Gene 8 (BRG8), conferring resistance to rice blast and bacterial blight diseases. Consistently, the BRG8 overexpression and complementation lines exhibited enhanced resistance to both pathogens. Subcellular localization assays showed that BRG8 localized in both cytoplasm and nucleus. More evidence revealed that nuclear-localized BRG8 enhanced rice immunity without hypersensitive response (HR)-like phenotype. Furthermore, we also demonstrated the CC domain of BRG8 not only physically interacted with itself, but also interacted with the KNOX Ⅱ protein HOMEOBOX ORYZA SATIVA59 (HOS59). Knockout of HOS59 in BRG8 background showed enhanced resistance to M. oryzae strain CH171 and Xoo strain CR4, similar to BRG8 background. In contrast, overexpression of HOS59 in BRG8 background, compromised the HR-like phenotype and resistance response. Further analysis revealed that HOS59 promotes the degradation of BRG8 via the 26S proteasome pathway. Collectively, our study highlights HOS59 as NLR immune regulators, fine-tune BRG8-mediated immune responses against pathogens, and provides new insights into NLR association and function in plant immunity.