The pan-tandem repeat map highlights multiallelic variants underlying gene expression and agronomic traits in rice.

Tandem repeats (TRs) are genomic regions that tandemly change in repeat number, which are often multiallelic. Their characteristics and contributions to gene expression and quantitative traits in rice are largely unknown. Here, we survey rice TR variations based on 231 genome assemblies and the rice pan-genome graph. We identify 227,391 multiallelic TR loci, including 54,416 TR variations that are absent from the Nipponbare reference genome. Only 1/3 TR variations show strong linkage with nearby bi-allelic variants (SNPs, Indels and PAVs). Using 193 panicle and 202 leaf transcriptomic data, we reveal 485 and 511 TRs act as QTLs independently of other bi-allelic variations to nearby gene expression, respectively. Using plant height and grain width as examples, we identify and validate TRs contributions to rice agronomic trait variations. These findings would enhance our understanding of the functions of multiallelic variants and facilitate rice molecular breeding.

A pan-TE map highlights transposable elements underlying domestication and agronomic traits in Asian rice.

Transposable elements (TEs) are ubiquitous genomic components and hard to study due to being highly repetitive. Here we assembled 232 chromosome-level genomes based on long-read sequencing data. Coupling the 232 genomes with 15 existing assemblies, we developed a pan-TE map comprising both cultivated and wild Asian rice. We detected 177 084 high-quality TE variations and inferred their derived state using outgroups. We found TEs were one source of phenotypic variation during rice domestication and differentiation. We identified 1246 genes whose expression variation was associated with TEs but not single-nucleotide polymorphisms (SNPs), such as OsRbohB, and validated OsRbohB's relative expression activity using a dual-Luciferase (LUC) reporter assays system. Our pan-TE map allowed us to detect multiple novel loci associated with agronomic traits. Collectively, our findings highlight the contributions of TEs to domestication, differentiation and agronomic traits in rice, and there is massive potential for gene cloning and molecular breeding by the high-quality Asian pan-TE map we generated.

Adjunctive therapy with an oral H2S donor provides additional therapeutic benefit beyond SGLT2 inhibition in cardiometabolic heart failure with preserved ejection fraction.

BACKGROUND AND PURPOSE: Sodium glucose cotransporter 2 inhibitors (SGLT2i) have emerged as a potent therapy for heart failure with preserved ejection fraction (HFpEF). Hydrogen sulphide (H2S), a well-studied cardioprotective agent, could be beneficial in HFpEF. SGLT2i monotherapy and combination therapy involving an SGLT2i and H2S donor in two preclinical models of cardiometabolic HFpEF was investigated. EXPERIMENTAL APPROACH: Nine-week-old C57BL/6N mice received L-NAME and a 60% high fat diet for five weeks. Mice were then randomized to either control, SGLT2i monotherapy or SGLT2i and H2S donor, SG1002, for five additional weeks. Ten-week-old ZSF1 obese rats were randomized to control, SGLT2i or SGLT2i and SG1002 for 8 weeks. SG1002 monotherapy was investigated in additional animals. Cardiac function (echocardiography and haemodynamics), exercise capacity, glucose handling and multiorgan pathology were monitored during experimental protocols. KEY RESULTS: SGLT2i treatment improved E/e' ratio and treadmill exercise in both models. Combination therapy afforded increases in cardiovascular sulphur bioavailability that coincided with improved left end-diastolic function (E/e' ratio), exercise capacity, metabolic state, cardiorenal fibrosis, and hepatic steatosis. Follow-up studies with SG1002 monotherapy revealed improvements in diastolic function, exercise capacity and multiorgan histopathology. CONCLUSIONS AND IMPLICATIONS: SGLT2i monotherapy remediated pathological complications exhibited by two well-established HFpEF models. Adjunctive H2S therapy resulted in further improvements of cardiometabolic perturbations beyond SGLT2i monotherapy. Follow-up SG1002 monotherapy studies inferred an improved phenotype with combination therapy beyond either monotherapy. These data demonstrate the differing effects of SGLT2i and H2S therapy while also revealing the superior efficacy of the combination therapy in cardiometabolic HFpEF.

Population-level exploration of alternative splicing and its unique role in controlling agronomic traits of rice.

Alternative splicing (AS) plays crucial roles in regulating various biological processes in plants. However, the genetic mechanisms underlying AS and its role in controlling important agronomic traits in rice (Oryza sativa) remain poorly understood. In this study, we explored AS in rice leaves and panicles using the rice minicore collection. Our analysis revealed a high level of transcript isoform diversity, with approximately one fifth of potential isoforms acting as major transcripts in both tissues. Regarding the genetic mechanism of AS, we found that the splicing of 833 genes in the leaf and 1,230 genes in the panicle was affected by cis-genetic variation. Twenty-one percent of these AS events could only be explained by large structural variations. Approximately 77.5% of genes with significant splicing quantitative trait loci (sGenes) exhibited tissue-specific regulation, and AS can cause 26.9% (leaf) and 23.6% (panicle) of sGenes to have altered, lost or gained functional domains. Additionally, through splicing-phenotype association analysis, we identified phosphate-starvation induced RING-type E3 ligase (OsPIE1; LOC_Os01g72480), whose splicing ratio was significantly associated with plant height. In summary, this study provides an understanding of AS in rice and its contribution to the regulation of important agronomic traits.

Uncovering key salt-tolerant regulators through a combined eQTL and GWAS analysis using the super pan-genome in rice.

For sessile plants, gene expression plays a pivotal role in responding to salinity stress by activating or suppressing specific genes. However, our knowledge of genetic variations governing gene expression in response to salt stress remains limited in natural germplasm. Through transcriptome analysis of the Global Mini-Core Rice Collection consisting of a panel of 202 accessions, we identified 22 345 and 27 610 expression quantitative trait loci associated with the expression of 7787 and 9361 eGenes under normal and salt-stress conditions, respectively, leveraging the super pan-genome map. Notably, combined with genome-wide association studies, we swiftly pinpointed the potential candidate gene STG5-a major salt-tolerant locus known as qSTS5. Intriguingly, STG5 is required for maintaining Na+/K+ homeostasis by directly regulating the transcription of multiple members of the OsHKT gene family. Our study sheds light on how genetic variants influence the dynamic changes in gene expression responding to salinity stress and provides a valuable resource for the mining of salt-tolerant genes in the future.

3D SHINKEI MR neurography in evaluation of traumatic brachial plexus.

3D SHINKEI neurography is a new sequence for imaging the peripheral nerves. The study aims at assessing traumatic brachial plexus injury using this sequence. Fifty-eight patients with suspected trauma induced brachial plexus injury underwent MR neurography (MRN) imaging in 3D SHINKEI sequence at 3 T. Surgery and intraoperative somatosensory evoked potentials or clinical follow-up results were used as the reference standard. MRN, surgery and electromyography (EMG) findings were recorded at four levels of the brachial plexus-roots, trunks, cords and branches. Fifty-eight patients had pre- or postganglionic injury. The C5-C6 nerve postganglionic segment was the most common (average 42%) among the postganglionic injuries detected by 3D SHINKEI MRN. The diagnostic accuracy (83.75%) and the specificity (90.30%) of MRN higher than that of EMG (p < 0.001). There was no significant difference in the diagnostic sensitivity of MRN compared with EMG (p > 0.05). Eighteen patients with brachial plexus injury underwent surgical exploration after MRN examination and the correlation between MRN and surgery was 66.7%. Due to the high diagnostic accuracy and specificity, 3D SHINKEI MRN can comprehensively display the traumatic brachial plexus injury. This sequence has great potential in the accurate diagnosis of traumatic brachial plexus injury.

Early Renal Denervation Attenuates Cardiac Dysfunction in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: The renal sympathetic nervous system modulates systemic blood pressure, cardiac performance, and renal function. Pathological increases in renal sympathetic nerve activity contribute to the pathogenesis of heart failure with preserved ejection fraction (HFpEF). We investigated the effects of renal sympathetic denervation performed at early or late stages of HFpEF progression. METHODS AND RESULTS: Male ZSF1 obese rats were subjected to radiofrequency renal denervation (RF-RDN) or sham procedure at either 8 weeks or 20 weeks of age and assessed for cardiovascular function, exercise capacity, and cardiorenal fibrosis. Renal norepinephrine and renal nerve tyrosine hydroxylase staining were performed to quantify denervation following RF-RDN. In addition, renal injury, oxidative stress, inflammation, and profibrotic biomarkers were evaluated to determine pathways associated with RDN. RF-RDN significantly reduced renal norepinephrine and tyrosine hydroxylase content in both study cohorts. RF-RDN therapy performed at 8 weeks of age attenuated cardiac dysfunction, reduced cardiorenal fibrosis, and improved endothelial-dependent vascular reactivity. These improvements were associated with reductions in renal injury markers, expression of renal NLR family pyrin domain containing 3/interleukin 1ß, and expression of profibrotic mediators. RF-RDN failed to exert beneficial effects when administered in the 20-week-old HFpEF cohort. CONCLUSIONS: Our data demonstrate that early RF-RDN therapy protects against HFpEF disease progression in part due to the attenuation of renal fibrosis and inflammation. In contrast, the renoprotective and left ventricular functional improvements were lost when RF-RDN was performed in later HFpEF progression. These results suggest that RDN may be a viable treatment option for HFpEF during the early stages of this systemic inflammatory disease.

A centromere map based on super pan-genome highlights the structure and function of rice centromeres.

Rice (Oryza sativa) is a significant crop worldwide with a genome shaped by various evolutionary factors. Rice centromeres are crucial for chromosome segregation, and contain some unreported genes. Due to the diverse and complex centromere region, a comprehensive understanding of rice centromere structure and function at the population level is needed. We constructed a high-quality centromere map based on the rice super pan-genome consisting of a 251-accession panel comprising both cultivated and wild species of Asian and African rice. We showed that rice centromeres have diverse satellite repeat CentO, which vary across chromosomes and subpopulations, reflecting their distinct evolutionary patterns. We also revealed that long terminal repeats (LTRs), especially young Gypsy-type LTRs, are abundant in the peripheral CentO-enriched regions and drive rice centromere expansion and evolution. Furthermore, high-quality genome assembly and complete telomere-to-telomere (T2T) reference genome enable us to obtain more centromeric genome information despite mapping and cloning of centromere genes being challenging. We investigated the association between structural variations and gene expression in the rice centromere. A centromere gene, OsMAB, which positively regulates rice tiller number, was further confirmed by expression quantitative trait loci, haplotype analysis and clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated protein 9 methods. By revealing the new insights into the evolutionary patterns and biological roles of rice centromeres, our finding will facilitate future research on centromere biology and crop improvement.

Neuralgic amyotrophy: sensitivity and specificity of magnetic resonance neurography in diagnosis: A retrospective study.

BACKGROUND: Neuralgic amyotrophy (NA) is a clinically acute or subacute disease. To study the characteristics of brachial plexus magnetic resonance neurography (MRN) in patients with NA, and to explore the clinical application value of MRN combined with electromyography (EMG) in the diagnosis of NA. METHODS: Brachial plexus MRN images of 32 patients with NA were retrospectively analyzed, and their characteristics were investigated. The accuracy, sensitivity and specificity of MRN, EMG, and the combination of the 2 methods for NA diagnosis were compared. RESULTS: Among the 32 patients with NA, 28 (87.5%) cases of unilateral brachial plexus involvement, 18 (56.3%) cases of multiple nerve roots involvement. In 10 cases, C5 nerve roots were involved alone, and in 9 cases, C5 to C6 nerve roots were involved together. The T2 signal intensity of the affected nerve increased, and 19 cases showed thickened and smooth nerve root edges. Twelve cases showed uneven thickening and segmental stenosis of the involved nerve roots. The diagnostic accuracy, sensitivity, and specificity of MRN for NA were higher than those of EMG. Combining MRN and EMG could improve the sensitivity and specificity of diagnosis. CONCLUSION: The main feature of MRN in patients with NA was that it was unilateral brachial plexus asymmetric involvement. The diagnostic effect of MRN was better than that of EMG. The combined diagnosis of MRN and EMG can help clinicians diagnose NA accurately.

A rice variation map derived from 10 548 rice accessions reveals the importance of rare variants.

Detailed knowledge of the genetic variations in diverse crop populations forms the basis for genetic crop improvement and gene functional studies. In the present study, we analyzed a large rice population with a total of 10 548 accessions to construct a rice super-population variation map (RSPVM), consisting of 54 378 986 single nucleotide polymorphisms, 11 119 947 insertion/deletion mutations and 184 736 presence/absence variations. Assessment of variation detection efficiency for different population sizes revealed a sharp increase of all types of variation as the population size increased and a gradual saturation of that after the population size reached 10 000. Variant frequency analysis indicated that ∼90% of the obtained variants were rare, and would therefore likely be difficult to detect in a relatively small population. Among the rare variants, only 2.7% were predicted to be deleterious. Population structure, genetic diversity and gene functional polymorphism of this large population were evaluated based on different subsets of RSPVM, demonstrating the great potential of RSPVM for use in downstream applications. Our study provides both a rich genetic basis for understanding natural rice variations and a powerful tool for exploiting great potential of rare variants in future rice research, including population genetics and functional genomics.

Research progress of the artificial intelligence application in wastewater treatment during 2012-2022: a bibliometric analysis.

This study identified literatures from the Web of Science Core Collection on the application of artificial intelligence in wastewater treatment from 2011 to 2022, through bibliometrics, to summarize achievements and capture the scientific and technological progress. The number of papers published is on the rise, and especially, the number of papers issued after 2018 has increased sharply, with China contributing the most in this regard, followed by the US, Iran and India. The University of Tehran has the largest number of papers, WATER is the most published journal, and Nasr M has the largest number of articles. Collaborative network has been developed mainly through cooperation between European countries, China and the US. Remote sensing in developing countries needs to be further integrated with water quality monitoring programs. It is worth noting that artificial neural network is a research hotspot in recent years. Through keyword clustering analysis, 'machine learning' and 'deep learning' are hot keywords that have emerged since 2019. The use of neural networks for predicting the effectiveness of treatment of difficult to degrade wastewater is a future research trend. The rapid advancement of deep learning provides the opportunity to build automated pipeline defect detection systems through image recognition.

Identification of natural allelic variation in TTL1 controlling thermotolerance and grain size by a rice super pan-genome.

Continuously increasing global temperatures present great challenges to food security. Grain size, one of the critical components determining grain yield in rice (Oryza sativa L.), is a prime target for genetic breeding. Thus, there is an immediate need for genetic improvement in rice to maintain grain yield under heat stress. However, quantitative trait loci (QTLs) endowing heat stress tolerance and grain size in rice are extremely rare. Here, we identified a novel negative regulator with pleiotropic effects, Thermo-Tolerance and grain Length 1 (TTL1), from the super pan-genomic and transcriptomic data. Loss-of-function mutations in TTL1 enhanced heat tolerance, and caused an increase in grain size by coordinating cell expansion and proliferation. TTL1 was shown to function as a transcriptional regulator and localized to the nucleus and cell membrane. Furthermore, haplotype analysis showed that hapL and hapS of TTL1 were obviously correlated with variations of thermotolerance and grain size in a core collection of cultivars. Genome evolution analysis of available rice germplasms suggested that TTL1 was selected during domestication of the indica and japonica rice subspecies, but still had much breeding potential for increasing grain length and thermotolerance. These findings provide insights into TTL1 as a novel potential target for the development of high-yield and thermotolerant rice varieties.

Effect of Quality of Life on Radiation Adherence for Patients With Cervical Cancer in an Urban Safety Net Health System.

PURPOSE: Outcomes for patients undergoing chemoradiation for cervical cancer are dependent on adherence to radiation therapy (RT). In other diseases, quality of life (QoL) is associated with treatment adherence, but the association between QoL and RT adherence for patients with cervical cancer remains unclear. METHODS AND MATERIALS: This prospective study included patients undergoing RT for cervical cancer from 2017 to 2021 at an urban safety net hospital. The Functional Assessment of Cancer Therapy-Cervical Cancer Version 4 was used to assess QoL based on 5 subscales (physical, functional, social and emotional, and cervical-cancer specific). The survey was administered at radiation consult, then weekly during RT and at follow-up. Patient information was abstracted from the medical record. Radiation nonadherence was defined as missing ≥2 days of external beam RT. The Functional Assessment of Cancer Therapy-Cervical Cancer Version 4 total and subscale scores were compared between adherent and nonadherent patients. Multivariable logistic regression was performed to control for confounding variables. RESULTS: Ninety-three patients were enrolled, completing 522 surveys. Median age at diagnosis was 46 years (interquartile range, 40-51); 76% of patients were Hispanic, and 12% were Black. Only 30% of patients were nonadherent with RT. A psychiatric comorbidity (P = .012) and symptomatic presentation (P = .027) were associated with decreased adherence. Baseline total QoL was higher in treatment-adherent than in nonadherent patients (median, 124.86; range, 48-160; 108.9, 46-150; P = .01). Higher baseline functional and physical subscale scores were associated with adherence (P < .05). Change from baseline to lowest score during treatment in the emotional subscale was also associated with patient adherence (P < .05). In multivariable analysis, higher baseline physical score, baseline total score, and change in emotional subscale score were associated with adherence (P < .05). CONCLUSIONS: Poor QoL during chemoradiation for cervical cancer is associated with missed treatments. Physician assessment of a patient's well-being while they are undergoing RT is of utmost importance to improve adherence to treatment.

Compared analysis with a high-quality genome of weedy rice reveals the evolutionary game of de-domestication.

The weedy rice (Oryza sativa f. spontanea) harbors large numbers of excellent traits and genetic diversities, which serves as a valuable germplasm resource and has been considered as a typical material for research about de-domestication. However, there are relatively few reference genomes on weedy rice that severely limit exploiting these genetic resources and revealing more details about de-domestication events. In this study, a high-quality genome (~376.4 Mb) of weedy rice A02 was assembled based on Nanopore ultra-long platform with a coverage depth of about 79.3× and 35,423 genes were predicted. Compared to Nipponbare genome, 5,574 structural variations (SVs) were found in A02. Based on super pan-genome graph, population SVs of 238 weedy rice and cultivated rice accessions were identified using public resequencing data. Furthermore, the de-domestication sites of weedy rice and domestication sites of wild rice were analyzed and compared based on SVs and single-nucleotide polymorphisms (SNPs). Interestingly, an average of 2,198 genes about de-domestication could only be found by F ST analysis based on SVs (SV-F ST) while not by F ST analysis based on SNPs (SNP-F ST) in divergent region. Additionally, there was a low overlap between domestication and de-domestication intervals, which demonstrated that two different mechanisms existed in these events. Our finding could facilitate pinpointing of the evolutionary events that had shaped the genomic architecture of wild, cultivated, and weedy rice, and provide a good foundation for cloning of the superior alleles for breeding.

Heavy Metal Pollution and Health Risk Assessment of Vegetable-Soil Systems of Facilities Irrigated with Wastewater in Northern China.

Soil pollution by heavy metals is a major concern in China and has received much attention in recent years. Aiming to investigate the status of heavy metal pollution and the safety of vegetables in the soil of wastewater-irrigated facilities, this study investigated the distribution and migration characteristics of heavy metals in vegetable−soil systems of facilities in a typical sewage irrigation area of the Xi River, Shenyang City, northern China. Health risks due to the fact of exposure to heavy metals in the vegetable soil of facilities and ingrown vegetables through different exposure pathways were evaluated. Spatial interpolation and a potential ecological risk assessment were applied to evaluate the soil quality. Bioaccumulation factors (BCFs) were used to analyze the absorption and transportation capacity of Cd, Cu, Pb, and Zn by different parts of different vegetables. The results showed that the average concentration of Cd exceeded the standard values by 1.82 times and accumulated by 11 times, suggesting that Cd poses the most severe pollution among the four metals in the soil of facilities in the Xi River sewage irrigation area. In the city, a significant accumulation of Cd in the soil was identified with different spatial distributions. Cd also contributed the most in terms of the estimated potential ecological risk index, while the impacts of the other three metals were relatively small. The concentrations of heavy metals were mostly lower than the limit set by the corresponding Chinese standards. Various BCFs were observed for the four metals in the order Cd > Zn > Cu > Pb. Vegetables also demonstrated different BCFs in the order of leaf vegetables > Rhizome vegetable > Solanaceae vegetable. The magnitude of the noncarcinogenic risk for all four heavy metals was less than one for all three exposure routes and did not cause significant noncarcinogenic health effects in humans. However, the carcinogenic risk of Cd from some vegetables via dietary intake was considered higher. Protection measures should be taken to implement better pollution control and land use planning.

Effects of Wx Genotype, Nitrogen Fertilization, and Temperature on Rice Grain Quality.

Quality is a complex trait that is not only the key determinant of the market value of the rice grain, but is also a major constraint in rice breeding. It is influenced by both genetic and environmental factors. However, the combined effects of genotypes and environmental factors on rice grain quality remain unclear. In this study, we used a three-factor experimental design to examine the grain quality of different Wx genotypes grown under different nitrogen fertilization and temperature conditions during grain development. We found that the three factors contributed differently to taste, appearance, and nutritional quality. Increased Wx function and nitrogen fertilization significantly reduced eating quality, whereas high temperature (HT) had almost no effect. The main effects of temperature on appearance quality and moderate Wx function at low temperatures (LTs) contributed to better appearance, and higher nitrogen fertilization promoted appearance at HTs. With regard to nutritional quality, Wx alleles promoted amylose content (AC) as well as starch-lipids content (SLC); nitrogen fertilization increased storage protein content (PC); and higher temperature increased lipid content but decreased the PC. This study helps to broaden the understanding of the major factors that affect the quality of rice and provides constructive messages for rice quality improvement and the cultivation of high-quality rice varieties.

Red fluorescent AIEgens based multifunctional nonviral gene vectors for the efficient combination of gene therapy and photodynamic therapy in anti-cancer.

Precise molecular engineering of AIEgens-based cationic delivery systems for high transfection efficiency (TE) and effective photodynamic therapy (PDT) holds a huge potential for cancer treatment. Herein, three amphiphiles (DT-C6/8/12-M) consisting of di(triazole-[12]aneN3) (M) and 1,1-dicyano-2-phenyl-2-(4-diphenylamino)phenyl-ethylene (DT) units have been developed to achieve luminescent tracking, efficient TE, and effective PDT in vitro and in vivo. These compounds exhibited strong aggregated induced emission (AIE) at 630 nm and mega Stokes shifts of up to 160 nm. They were able to bind DNA into nanoparticles with suitable sizes, positive surface potential, and good biocompatibility in the presence of DOPE. Among them, vector DT-C12-M/DOPE with n-dodecyl linker achieved a transfection efficiency as high as 42.3 folds that of Lipo2000 in PC-3 cell lines. DT-C12-M/DOPE exhibited the capability of successful endo/lysosomal escape and rapid nuclear delivery of pDNA, and the gene delivery process was clearly monitored via confocal laser scanning microscopy. Moreover, efficient reactive oxygen species (ROS) generation by DT-C12-M upon light irradiation led to effective PDT in vitro . We further show that combination of p53 gene therapy and PDT dramatically enhanced cancer therapeutic outcome in vivo. This "three birds, one stone" strategy offers a novel and promising approach for real-time tracking of gene delivery and better cancer treatment.

A super pan-genomic landscape of rice.

Pan-genomes from large natural populations can capture genetic diversity and reveal genomic complexity. Using de novo long-read assembly, we generated a graph-based super pan-genome of rice consisting of a 251-accession panel comprising both cultivated and wild species of Asian and African rice. Our pan-genome reveals extensive structural variations (SVs) and gene presence/absence variations. Additionally, our pan-genome enables the accurate identification of nucleotide-binding leucine-rich repeat genes and characterization of their inter- and intraspecific diversity. Moreover, we uncovered grain weight-associated SVs which specify traits by affecting the expression of their nearby genes. We characterized genetic variants associated with submergence tolerance, seed shattering and plant architecture and found independent selection for a common set of genes that drove adaptation and domestication in Asian and African rice. This super pan-genome facilitates pinpointing of lineage-specific haplotypes for trait-associated genes and provides insights into the evolutionary events that have shaped the genomic architecture of various rice species.