Integration of genome-wide association study, linkage analysis, and population transcriptome analysis to reveal the TaFMO1-5B modulating seminal root growth in bread wheat.

Bread wheat, one of the keystone crops for global food security, is challenged by climate change and resource shortage. The root system plays a vital role in water and nutrient absorption, making it essential for meeting the growing global demand. Here, using an association-mapping population composed of 406 accessions, we identified QTrl.Rs-5B modulating seminal root development with a genome-wide association study and validated its genetic effects with two F5 segregation populations. Transcriptome-wide association study prioritized TaFMO1-5B, a gene encoding the flavin-containing monooxygenases, as the causal gene for QTrl.Rs-5B, whose expression levels correlate negatively with the phenotyping variations among our population. The lines silenced for TaFMO1-5B consistently showed significantly larger seminal roots in different genetic backgrounds. Additionally, the agriculture traits measured in multiple environments showed that QTrl.Rs-5B also affects yield component traits and plant architecture-related traits, and its favorable haplotype modulates these traits toward that of modern cultivars, suggesting the application potential of QTrl.Rs-5B for wheat breeding. Consistently, the frequency of the favorable haplotype of QTrl.Rs-5B increased with habitat expansion and breeding improvement of bread wheat. In conclusion, our findings identified and demonstrated the effects of QTrl.Rs-5B on seminal root development and illustrated that it is a valuable genetic locus for wheat root improvement.

Left atrial strain brings new insights for evaluating early diastolic dysfunction in patients with well-functioning bicuspid aortic valve.

BACKGROUND: Left atrial reservoir strain (LARS) is an early sensor of left ventricular (LV) diastolic dysfunction. Still, the clinical implications of LARS in patients with well-functioning bicuspid aortic valve (BAV) remain unknown. MATERIALS: The study recruited 103 patients with well-functioning BAV and 50 controls with tricuspid aortic valves. LARS, LV global longitudinal strain (LVGLS) and aortic elasticity indices (aortic strain, aortic distensibility and stiffness index) were acquired. This study aimed to analyze the changes of LARS and further explore the influential factors of LARS in patients with well-functioning BAV. RESULTS: Patients with BAV had lower LARS (34.17 ± 4.85 vs. 44.72 ± 6.06 %, P < .001) and LVGLS (20.53 ± 1.28 vs. 22.30 ± .62 %, P < .001), and abnormal aortic elasticity indices (aortic strain:7.14 ± 1.57 vs. 10.99 ± 1.03 %, aortic distensibility: 5.82 ± 1.50 vs. 8.98 ± 2.42 (10-6 cm2 dyne-1 ), and stiffness index: 6.30 ± 2.30 vs. 3.92 ± .98, all P < .05) compared with controls. LARS was associated with LVGLS (r = .799), interventricular septum index (r = -.232), lateral e' (r = .290), septal e' (r = .308), E/e' ratio (r = -.392), aortic strain (r = .829), aortic distensibility (r = .361), and stiffness index (r = -.724) (all P < .05). LVGLS, aortic strain and E/e' ratio were independent influencers of LARS in the multifactorial analysis model (all P < .05). CONCLUSION: In patients with well-functioning BAV, decreased LARS may provide evidence of subclinical LV diastolic function impairment. LARS may be helpful for clinical risk stratification in such a population.

MLP-based classification of COVID-19 and skin diseases.

Recent years have witnessed a growing interest in neural network-based medical image classification methods, which have demonstrated remarkable performance in this field. Typically, convolutional neural network (CNN) architectures have been commonly employed to extract local features. However, the transformer, a newly emerged architecture, has gained popularity due to its ability to explore the relevance of remote elements in an image through a self-attention mechanism. Despite this, it is crucial to establish not only local connectivity but also remote relationships between lesion features and capture the overall image structure to improve image classification accuracy. Therefore, to tackle the aforementioned issues, this paper proposes a network based on multilayer perceptrons (MLPs) that can learn the local features of medical images on the one hand and capture the overall feature information in both spatial and channel dimensions on the other hand, thus utilizing image features effectively. This paper has been extensively validated on COVID19-CT dataset and ISIC 2018 dataset, and the results show that the method in this paper is more competitive and has higher performance in medical image classification compared with existing methods. This shows that the use of MLP to capture image features and establish connections between lesions is expected to provide novel ideas for medical image classification tasks in the future.

CDK5 Upregulated by ELF3 Transcription Promotes IL-1ß-induced Inflammation and Extracellular Matrix Degradation in Human Chondrocytes.

Osteoarthritis (OA) is a common chronic disease with age-associated increase in both incidence and prevalence. The cyclin-dependent kinase 5 (CDK5), which is a member of the CDK family, is involved in many chronic diseases. This study was performed to explore the functional role of CDK5 in OA and to discuss the detailed molecular mechanisms. The expressions of CDK5 and ELF3 before or after transfection were detected with reverse transcription-quantitative PCR (RT-qPCR) and western blot. 5-ethynyl-2'-deoxyuridine (Edu) and terminal deoxynucleoitidyl transferase-mediated nick-end labeling (TUNEL) assays were used to detect the proliferation and apoptosis of C28/I2 cells. The levels of inflammatory cytokines were estimated using enzyme-linked immunosorbent assay (ELISA) while the expressions of proteins implicated in extracellular matrix (ECM) degradation- and apoptosis were detected using western blot. Additionally, the activity of CDK5 promoters and its binding with ELF3 were detected using luciferase activity assay and chromatin immunoprecipitation (CHIP) assay. In the present study, it was discovered that the mRNA and protein expressions of CDK5 were significantly increased in IL-1ß-induced C28/I2 cells. After depleting CDK5 expression, the apoptosis, inflammation and ECM in C28/I2 cells with IL-1ß induction were suppressed. It was also found that ELF3 expression was increased in IL-1ß-induced C28/I2 cells and acted as a transcription factor binding to the CDK5 promoter to regulate its transcriptional expression. The further experiments evidenced that ELF3 overexpression partially reversed the inhibitory effects of CDK5 deficiency on IL-1ß-induced apoptosis, inflammation and ECM in C28/I2 cells. Collectively, CDK5 that upregulated by ELF3 transcription could promote the development of OA.

Multi-Wavelength Narrow-Spacing Laser Frequency Stabilization Technology Based on Fabry-Perot Etalon.

Classical frequency-stabilized lasers have achieved high-frequency stability and reproducibility; however, their extensive wavelength spacing limits their utility in various scenarios. This study introduces a novel frequency-stabilized laser scheme that integrates a Fabry-Perot etalon (FPE) with digital control technology and wavelength modulation techniques. The FPE, characterized by multiple transmission peaks at minimal frequency intervals, provides stable frequency references for different lasers, thereby enhancing the system's flexibility and adaptability. An error signal is derived from the first-order differentiation of the FPE's transmission curve. A 180° phase difference was observed in the feedback output signal when the laser's central frequency diverged from the reference, determining that the direction of the frequency control was accordingly determined.Employing feedback control, the laser's output frequency is stabilized at the transmission peak frequency of the FPE. Experimental results demonstrate that this stabilization scheme effectively locks the laser's output wavelength to different transmission peak frequencies of the FPE, achieving 25 GHz wavelength spacing. The frequency stability is improved by two orders of magnitude on a second-level timescale, maintained within hundreds of kHz, equating to a frequency stability level of 10-10.

Risk factors for the recurrence of left atrioventricular valvular regurgitation after surgical repair of partial and transitional atrioventricular septal defect.

Background: Left atrioventricular valvular regurgitation (LAVVR) recurrence after partial and transitional atrioventricular septal defect (AVSD) repair is the main risk factor associated with reoperation or mortality. The purpose of this study was to identify risk factors associated with the recurrence of LAVVR after surgical repair of transitional and partial AVSD at a single institution. Methods: A hundred and fifty-seven patients who underwent anatomical repair for partial and transitional AVSD from January 2013 to December 2021 were included in our institutional database. Demographic characteristics, operative information, comorbidities, complications, and outcomes were retrieved from electronic medical records. Echocardiographic evaluations included cardiac dimensions, the degree of LAVVR, and the anatomy of the atrioventricular valve. Results: After a median follow-up period of 5.8 years, 40 patients had recurrent moderate or even more severe LAVVR. Compared with patients without recurrent LAVVR, those experiencing LAVVR recurrence were more likely to have larger preoperative left atrial (LA) size and larger left ventricular (LV) size after standardization, larger left atrioventricular valve (LAVV) cleft width, higher proportions of preoperative moderate or even more severe LAVVR, and immediately postoperative mild to moderate or even more severe LAVVR. Univariate Cox regression analysis showed that age at first repair, height, LA size after standardization, LV size after standardization, the severity of preoperative LAVVR, immediately postoperative LAVVR, and the LAVV cleft width more than 1cm were risk factors for recurrent LAVVR (P<0.05 for all). Multivariable Cox regression analysis showed that mild to moderate or even more severe LAVVR postoperatively [hazard ratio (HR) 9.53, 95% confidence interval (CI): 3.78-24.01; P<0.001], the width of LAVV cleft more than 1 cm (HR: 3.90, 95% CI: 1.80-8.48; P<0.001) and age at first repair (HR: 0.45, 95% CI: 0.31-0.66; P<0.001) were independently associated with the recurrence of LAVVR. Conclusions: The width of LAVV cleft, mild to moderate or even more severe LAVVR immediately after surgery, and age at initial surgery are risk factors for recurrent LAVVR. The presence of recurrent LAVVR necessitates proactive surveillance to facilitate timely reintervention.

Prognostic Implications of Left Atrial Strain in Bicuspid Aortic Valve With Chronic Aortic Regurgitation.

BACKGROUND: Left atrial reservoir strain (LARS) is a novel imaging biomarker of left ventricular diastolic dysfunction. This study aimed to examine the prognostic implications of LARS in patients with bicuspid aortic valve and significant (moderate-severe to severe) aortic regurgitation. METHODS AND RESULTS: A total of 220 patients with bicuspid aortic valve and significant aortic regurgitation were prospectively enrolled in our study. LARS and left ventricular global longitudinal strain were derived from speckle-tracking echocardiography. The end point was a composite of all-cause mortality, heart failure hospitalization, and aortic valve repair or replacement. The threshold value of LARS <24% was used to identify impaired left atrial mechanics based on prior results. During a median follow-up of 364 (interquartile range, 294-752) days, 46 patients (20.9%) reached the composite end points. On multivariable Cox analysis, impaired LARS (adjusted hazard ratio, 2.08 [95% CI, 1.05-4.11]; P=0.036) was a statistically significant predictor of composite end points after adjustment for other statistically significant predictors. Finally, adding impaired LARS to other statistically significant predictors (New York Heart Association functional class and left ventricular global longitudinal strain) significantly improved the global χ2 (from 32.19 to 36.56; P=0.037) and reclassification (continuous net reclassification index=0.55; P<0.001) of the prediction model. CONCLUSIONS: In patients with bicuspid aortic valve and significant aortic regurgitation, the impairment of LARS is a strong independent prognostic predictor and confers incremental prognostic utility over clinical and other echocardiographic parameters. These findings suggest that LARS could be considered in risk stratification for such populations.

Hijacking of host mitochondria by Toxoplasma gondii and SARS-CoV-2.

Mitochondria regulate energy production, cell cycle, and immune signaling. Li et al. recently reported that Toxoplasma gondii induces the shedding of mitochondrial outer membrane to promote its growth. Intriguingly, the hijacking of host mitochondria has been shown to play an essential role in the pathogenesis of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Bionic Nonsmooth Drag Reduction Mathematical Model Construction and Subsoiling Verification.

In this study, a bionic nonsmooth drag-reducing surface design method was proposed; a mathematical model was developed to obtain the relationship between the altitude of the nonsmooth drag-reducing surface bulges and the spacing of two bulges, as well as the speed of movement, based on which two subsoiler shovel tips were designed and verified on field experiments. The mechanism of nonsmooth surface drag reduction in soil was analyzed, inspired by the efficient digging patterns of antlions. The nonsmooth surface morphology of the antlion was acquired by scanning electron microscopy, and a movement model of the nonsmooth surface in soil was developed, deriving that the altitude of the nonsmooth drag-reducing surface bulge is proportional to the square of the distance between two bulges and inversely proportional to the square of the movement speed. A flat subsoiler shovel tip and a curved tip were designed by applying this model, and the smooth subsoiler shovel tips and the pangolin scale bionic tips were used as controls, respectively. The effect of the model-designed subsoilers on drag reduction was verified by subsoiling experiments in the field. The results showed that the resistance of the model-designed curved subsoiler was the lowest, the resistance of the pangolin scale bionic subsoiler was moderate, and the resistance of the smooth surface subsoiler was the highest; the resistance of the curved subsoiler was less than the flat subsoilers; the resistance reduction rate of the model-designed curved subsoiler was 24.6% to 33.7% at different depths. The nonsmooth drag reduction model established in this study can be applied not only to the design of subsoilers but also to the design of nonsmooth drag reduction surfaces of other soil contacting parts.

A Unique Type of Highly-Activated Microglia Evoking Brain Inflammation via Mif/Cd74 Signaling Axis in Aged Mice.

Senescence-associated alterations of microglia have only recently been appreciated in the aged brain. Although our previous study has reported chronic inflammation in aged microglia, the mechanism remains poorly understood. Here, we performed morphological detection and transcriptomic analysis of aged microglia at the single cell level. Aged mice showed a large quantity and a large body volume of microglia in the brain. Six subgroups of microglia with unique function were identified by single cell RNA sequencing. Three out of six subgroups showed dramatic variations in microglia between aged and young mice. A unique type of highly-activated microglia (HAM) was observed in aged mice only, with specific expression of several markers, including Lpl, Lgals3, Cst7, and Cd74. Gene clusters with functional implications in cell survival, energy metabolism, and immuno-inflammatory responses were markedly activated in HAM. Mechanistically, neuron-released Mif, acting through Cd74 receptor in HAM, promoted the immunochemotactic activity of microglia, which then triggered immuno-inflammatory responses in aged brains. These findings may reveal new targets for reducing age-related brain inflammation to maintain brain health.

Global Profiling of Dynamic Alternative Splicing Modulation in Arabidopsis Root upon Ralstonia solanacearum Infection.

Alternative splicing (AS) is an important mechanism by which eukaryotes regulate transcription and protein diversity. The dynamic changes in AS that occur on a genome-wide scale during interactions between plant roots and pathogens remain unknown. Here, we used the interaction between Arabidopsis and Ralstonia solanacearum as a model to explore the AS changes that take place during the response of roots to infection by means of high-throughput RNA-sequencing. We showed that dynamic changes in AS occur much earlier than changes at the level of transcription during R.solanacearum infection. Comparing genes that are regulated at the transcriptional and AS levels indicated that there are few common genes between differentially spliced genes (DSGs) and differentially expressed genes (DEGs). The functional gene ontology (GO) analysis identified that the enriched GO terms for the DSGs were different from those of the DEGs. The DSGs were over-represented in GO terms associated with post-transcriptional and translational regulations, suggesting that AS may act on RNA stability and during post-translation, thus affecting the output of plant defense molecules. Meanwhile, changes in DSGs were infection stage-specific. Furthermore, the nucleotide binding domain and leucine-rich repeat proteins and receptor-like kinases, key regulators in plant immunity, were shown to undergo dynamic changes in AS in response to R. solanacearum. Taken together, AS, along with transcription, modulates plant root defense to R. solanacearum through transcriptome reprogramming.

A quick and efficient hydroponic potato infection method for evaluating potato resistance and Ralstonia solanacearum virulence.

BACKGROUND: Potato, the third most important crop worldwide, plays a critical role in human food security. Brown rot, one of the most destructive potato diseases caused by Ralstonia solanacearum, results in huge economic losses every year. A quick, stable, low cost and high throughout method is required to meet the demands of identification of germplasm resistance to bacterial wilt in potato breeding programs. RESULTS: Here we present a novel R. solanacearum hydroponic infection assay on potato plants grown in vitro. Through testing wilt symptom appearance and bacterial colonization in aerial part of plants, we found that the optimum conditions for in vitro potato infection were using an OD600 0.01 bacterial solution suspended with tap water for infection, broken potato roots and an open container. Infection using R. solanacearum strains with differential degree of aggressivity demonstrated that this infection system is equally efficient as soil-drench inoculation for assessment of R. solanacearum virulence on potato. A small-scale assessment of 32 potato germplasms identified three varieties highly resistant to the pathogen, which indicates this infection system is a useful method for high-throughout screening of potato germplasm for resistance. Furthermore, we demonstrate the utility of a strain carrying luminescence to easily quantify bacterial colonization and the detection of latent infections in hydroponic conditions, which can be efficiently used in potato breeding programs. CONCLUSIONS: We have established a quick and efficient in vitro potato infection system, which may facilitate breeding for new potato cultivars with high resistance to R. solanacearum.

Rhodium-Catalyzed Synthesis of α,ß-Unsaturated Ketones through Sequential C-C Coupling and Redox Isomerization.

A novel Rh(I)-catalyzed sequential C-C coupling and redox isomerization between allylic alcohols and 1,3-dienes has been accomplished. This versatile protocol provides expeditious access to a broad range of polysubstituted α,ß-unsaturated ketones with excellent atom economy and regioselectivity.

Chemical constituents from Melastoma dodecandrum and their inhibitory activity on interleukin-8 production in HT-29 cells.

In search of anti-inflammatory lead compounds from traditional Chinese medicines, a bioassay-guided phytochemical study on Melastoma dodecandrum was carried out. As a result, 18 compounds have been isolated. Their chemical structures were determined on the basis of their physicochemical properties and spectral data. Among the isolates, three pentacyclic triterpenoids, ursolic acid (1), asiatic acid (3) and terminolic acid (6), together with one tannin casuarinin (17), were found to significantly decrease interleukin-8 (IL-8) production in human colon cancer cells. The results imply, at least in part, that the anti-inflammatory effect of M. dodecandrum could be due to inhibition of IL-8 production, demonstrated by these naturally occurring compounds described above.