Genome-wide association study reveals genetic loci for ten trace elements in foxtail millet (Setaria italica).

KEY MESSAGE: One hundred and fifty-five QTL for trace element concentrations in foxtail millet were identified using a genome-wide association study, and a candidate gene associated with Ni-Co-Cr concentrations was detected. Foxtail millet (Setaria italica) is an important regional crop known for its rich mineral nutrient content, which has beneficial effects on human health. We assessed the concentrations of ten trace elements (Ba, Co, Cr, Cu, Fe, Mn, Ni, Pb, Sr, and Zn) in the grain of 408 foxtail millet accessions. Significant differences in the concentrations of five elements (Ba, Co, Ni, Sr, and Zn) were observed between two subpopulations of spring- and summer-sown foxtail millet varieties. Moreover, 84.4% of the element pairs exhibited significant correlations. To identify the genetic factors influencing trace element accumulation, a comprehensive genome-wide association study was conducted, identifying 155 quantitative trait locus (QTL) for the ten trace elements across three different environments. Among them, ten QTL were consistently detected in multiple environments, including qZn2.1, qZn4.4, qCr4.1, qFe6.3, qFe6.5, qCo6.1, qPb7.3, qPb7.5, qBa9.1, and qNi9.1. Thirteen QTL clusters were detected for multiple elements, which partially explained the correlations between elements. Additionally, the different concentrations of five elements between foxtail millet subpopulations were caused by the different frequencies of high-concentration alleles associated with important marker-trait associations. Haplotype analysis identified a candidate gene SETIT_036676mg associated with Ni accumulation, with the GG haplotype significantly increasing Ni-Co-Cr concentrations in foxtail millet. A cleaved amplified polymorphic sequence marker (cNi6676) based on the two haplotypes of SETIT_036676mg was developed and validated. Results of this study provide valuable reference information for the genetic research and improvement of trace element content in foxtail millet.

Bibliometric analysis: Hot spots and frontiers in acupuncture treatment of cerebral infarction.

OBJECTIVE: CiteSpace6.1.R2 is used to analyze the research status of acupuncture in the treatment of cerebral infarction, and to find relevant hot spots and frontiers. METHODS: The researchers searched the Web of Science Core Collection database. The search date is from the establishment of the database to August 31, 2023. The search terms and expressions are: ("Cerebral Infarction" OR "Ischemic stroke") AND ("Acupuncture" OR "fire needle"). The researchers used CiteSpace software to draw a knowledge map to explore the hot spots and frontiers of acupuncture in treating cerebral infarction. RESULTS: We screened 414 articles in the Web of Science Core Collection database. China is the country with the largest number of publications, with a total of 343 papers published. China's institutions cooperate most closely, and cooperation between countries is less and more scattered. The author with the highest number of published articles is Chen L, with a total of 31 published articles. The research focus mainly revolves around the mechanism of acupuncture treatment of cerebral infarction and electroacupuncture treatment of cerebral infarction. Among them, acupuncture treatment of cerebral infarction is the most. CONCLUSION: According to CiteSpace's analysis results, China is at the forefront of this research field, while other countries have less research in this field and little cooperation among countries. At present, the mainstream aspect of research is the mechanism of acupuncture treatment of cerebral infarction electroacupuncture and acupuncture points. Therefore, in future research, we should pay more attention to the treatment of cerebral infarction mechanism of acupuncture, problems with the type of acupuncture used, and acupuncture points.

Efficient identification of QTL for agronomic traits in foxtail millet (Setaria italica) using RTM- and MLM-GWAS.

KEY MESSAGE: Eleven QTLs for agronomic traits were identified by RTM- and MLM-GWAS, putative candidate genes were predicted and two markers for grain weight were developed and validated. Foxtail millet (Setaria italica), the second most cultivated millet crop after pearl millet, is an important grain crop in arid regions. Seven agronomic traits of 408 diverse foxtail millet accessions from 15 provinces in China were evaluated in three environments. They were clustered into two divergent groups based on genotypic data using ADMIXTURE, which was highly consistent with their geographical distribution. Two models for genome-wide association studies (GWAS), namely restricted two-stage multi-locus multi-allele (RTM)-GWAS and mixed linear model (MLM)-GWAS, were used to dissect the genetic architecture of the agronomic traits based on 13,723 SNPs. Eleven quantitative trait loci (QTLs) for seven traits were identified using two models (RTM- and MLM-GWAS). Among them, five were considered stable QTLs that were identified in at least two environments using MLM-GWAS. One putative candidate gene (SETIT_006045mg, Chr4: 744,701-746,852) that can enhance grain weight per panicle was identified based on homologous gene comparison and gene expression analysis and was validated by haplotype analysis of 330 accessions with high-depth (10×) resequencing data (unpublished). In addition, homologous gene comparison and haplotype analysis identified one putative foxtail millet ortholog (SETIT_032906mg, Chr2: 5,020,600-5,029,771) with rice affecting the target traits. Two markers (cGWP6045 and kTGW2906) were developed and validated and can be used for marker-assisted selection of foxtail millet with high grain weight. The results provide a fundamental resource for foxtail millet genetic research and breeding and demonstrate the power of integrating RTM- and MLM-GWAS approaches as a complementary strategy for investigating complex traits in foxtail millet.

A homogeneous label-free electrochemical aptasensor based on an omega-like DNA nanostructure for progesterone detection.

A novel homogeneous label-free electrochemical aptamer sensor for the detection of progesterone was prepared by combining a well-designed omega (Ω)-like DNA (Ω-DNA) nanostructure, with an isothermal cycling amplification strategy based on the highly efficient exonuclease III (Exo III). The omega-like (Ω) DNA is composed of two oligonucleotide strands: DNA1 and DNA2. The Pro aptamer triggers a chain displacement reaction of Ω-DNA nanostructures, forms a new double-stranded DNA structure (aptamer precursor-DNA2), and releases DNA1. Then, Exo III selectively cleaves the DNA duplex and releases the Pro aptamer to participate in a new displacement reaction. Meanwhile, the released DNA1 strands gain access to the strongly bound hemin, forming a hemin/G-quadruplex (DNAzyme). In the presence of hydrogen peroxide (H2O2), differential pulse voltammetry (DPV) was used to detect the current signal from the oxidation of o-phenylenediamine (OPD) to aminoazobenzene (DAP) catalyzed by DNAzyme. However, the amount of released DNA1 from the Ω-DNA nanostructures is reduced in the presence of the target Pro, and the DPV signal declines because of the small amount of DNAzyme formed. The developed electrochemical aptasensor has a wide dynamic linear relationship in the range of 1 pg mL-1 to 10 ng mL-1 under optimal conditions. Its detection limit is down to 0.3 pg mL-1, providing a potential platform for a sensitive Pro assay among electrochemical assays.

Combined linkage analysis and association mapping identifies genomic regions associated with yield-related and drought-tolerance traits in wheat (Triticum aestivum L.).

KEY MESSAGE: Combined linkage analysis and association mapping identified genomic regions associated with yield and drought tolerance, providing information to assist breeding for high yield and drought tolerance in wheat. Wheat (Triticum aestivum L.) is one of the most widely grown food crops and provides adequate amounts of protein to support human health. Drought stress is the most important abiotic stress constraining yield during the flowering and grain development periods. Precise targeting of genomic regions underlying yield- and drought tolerance-responsive traits would assist in breeding programs. In this study, two water treatments (well-watered, WW, and rain-fed water stress, WS) were applied, and five yield-related agronomic traits (plant height, PH; spike length, SL; spikelet number per spike, SNPS; kernel number per spike, KNPS; thousand kernel weight, TKW) and drought response values (DRVs) were used to characterize the drought sensitivity of each accession. Association mapping was performed on an association panel of 304 accessions, and linkage analysis was applied to a doubled haploid (DH) population of 152 lines. Eleven co-localized genomic regions associated with yield traits and DRV were identified in both populations. Many previously cloned key genes were located in these regions. In particular, a TKW-associated region on chromosome 2D was identified using both association mapping and linkage analysis and a key candidate gene, TraesCS2D02G142500, was detected based on gene annotation and differences in expression levels. Exonic SNPs were analyzed by sequencing the full length of TraesCS2D02G142500 in the association panel, and a rare haplotype, Hap-2, which reduced TKW to a lesser extent than Hap-1 under drought stress, and the Hap-2 varieties presented drought-insensitive. Altogether, this study provides fundamental insights into molecular targets for high yield and drought tolerance in wheat.

Accurate and fast small p-value estimation for permutation tests in high-throughput genomic data analysis with the cross-entropy method.

Permutation tests are widely used for statistical hypothesis testing when the sampling distribution of the test statistic under the null hypothesis is analytically intractable or unreliable due to finite sample sizes. One critical challenge in the application of permutation tests in genomic studies is that an enormous number of permutations are often needed to obtain reliable estimates of very small p-values, leading to intensive computational effort. To address this issue, we develop algorithms for the accurate and efficient estimation of small p-values in permutation tests for paired and independent two-group genomic data, and our approaches leverage a novel framework for parameterizing the permutation sample spaces of those two types of data respectively using the Bernoulli and conditional Bernoulli distributions, combined with the cross-entropy method. The performance of our proposed algorithms is demonstrated through the application to two simulated datasets and two real-world gene expression datasets generated by microarray and RNA-Seq technologies and comparisons to existing methods such as crude permutations and SAMC, and the results show that our approaches can achieve orders of magnitude of computational efficiency gains in estimating small p-values. Our approaches offer promising solutions for the improvement of computational efficiencies of existing permutation test procedures and the development of new testing methods using permutations in genomic data analysis.

Chitosan oligosaccharide attenuates acute kidney injury and renal interstitial fibrosis induced by ischemia-reperfusion.

Acute kidney injury (AKI) and renal interstitial fibrosis are global clinical syndromes associated with high morbidity and mortality. Renal ischemia-reperfusion (I/R) injury, which commonly occurs during surgery, is one of the major causes of AKI. Nevertheless, an efficient therapeutic approach for AKI and the development of renal interstitial fibrosis is still lacking due to its elusive pathogenetic mechanism. Here, we showed that chitosan oligosaccharide (COS), a natural oligomer polysaccharide degraded from chitosan, significantly attenuates I/R-induced AKI and maintains glomerular filtration function by inhibiting oxidative stress, mitochondrial damage, and excessive endoplasmic reticulum stress both in vitro and in vivo. In addition, long-term administration of COS can also attenuate the proliferation of myofibroblasts, mitigate extra cellular matrix deposition, and thus inhibit the transition of AKI to chronic kidney disease through participating in metabolic and redox biological processes. Our findings provide novel insights into the protective role of COS against acute kidney injury.

An Explicit-Correction-Force Scheme of IB-LBM Based on Interpolated Particle Distribution Function.

In order to obtain a better numerical simulation method for fluid-structure interaction (FSI), the IB-LBM combining the lattice Boltzmann method (LBM) and immersed boundary method (IBM) has been studied more than a decade. For this purpose, an explicit correction force scheme of IB-LBM was proposed in this paper. Different from the current IB-LBMs, this paper introduced the particle distribution function to the interpolation process from the fluid grids to the immersed boundary at the mesoscopic level and directly applied the LBM force models to obtain the interface force with a simple form and explicit process. Then, in order to ensure the mass conservation in the local area of the interface, this paper corrected the obtained interface force with the correction matrix, forming the total explicit-correction-force (ECP) scheme of IB-LBM. The results of four numerical tests were used to verify the order of accuracy and effectiveness of the present method. The streamline penetration is limited and the numerical simulation with certain application significance is successful for complex boundary conditions such as the movable rigid bodies (free oscillation of the flapping foil) and flexible deformable bodies (free deformation of cylinders). In summary, we obtained a simple and alternative simulation method that can achieve good simulation results for engineering reference models with complex boundary problems.

SiMYBS3, Encoding a Setaria italica Heterosis-Related MYB Transcription Factor, Confers Drought Tolerance in Arabidopsis.

Drought is a major limiting factor affecting grain production. Drought-tolerant crop varieties are required to ensure future grain production. Here, 5597 DEGs were identified using transcriptome data before and after drought stress in foxtail millet (Setaria italica) hybrid Zhangza 19 and its parents. A total of 607 drought-tolerant genes were screened through WGCNA, and 286 heterotic genes were screened according to the expression level. Among them, 18 genes overlapped. One gene, Seita.9G321800, encoded MYBS3 transcription factor and showed upregulated expression after drought stress. It is highly homologous with MYBS3 in maize, rice, and sorghum and was named SiMYBS3. Subcellular localization analysis showed that the SiMYBS3 protein was located in the nucleus and cytoplasm, and transactivation assay showed SiMYBS3 had transcriptional activation activity in yeast cells. Overexpression of SiMYBS3 in Arabidopsis thaliana conferred drought tolerance, insensitivity to ABA, and earlier flowering. Our results demonstrate that SiMYBS3 is a drought-related heterotic gene and it can be used for enhancing drought resistance in agricultural crop breeding.

Modeling and Simulation of Autonomous Inflow Control Devices for Gas Exploitation.

Horizontal well technology is an efficient method of oil and gas exploitation. The goal of increasing oil production and improving productivity can be achieved by increasing the contact area between the reservoir and the wellbore. The presence of bottom water cresting reduces the efficiency of oil and gas production significantly. Autonomous inflow control devices (AICDs) are widely used to delay the influx of water into the wellbore. Two kinds of AICDs are proposed to restrain the bottom water breakthrough during natural gas production. The fluid flows in the AICDs are simulated numerically. The pressure difference between the inlet and outlet is calculated to evaluate the ability of blocking the flow. A dual-inlet design can increase the flow rate of AICDs, thus enhancing the water blocking effect. Numerical simulations show that the devices can block water flowing into the wellbore effectively.

Transient targeting of BIM-dependent adaptive MCL1 preservation enhances tumor response to molecular therapeutics in non-small cell lung cancer.

Despite remarkable efficacy, targeted treatments often yield a subpopulation of residual tumor cells in part due to non-genetic adaptions. Previous mechanistic understanding on the emergence of these drug-tolerant persisters (DTPs) has been limited to epigenetic and transcriptional reprogramming. Here, by comprehensively interrogating therapy-induced early dynamic protein changes in diverse oncogene-addicted non-small cell lung cancer models, we identified adaptive MCL1 increase as a new and universal mechanism to confer apoptotic evasion and DTP formation. In detail, acute MAPK signaling disruption in the presence of genotype-based tyrosine kinase inhibitors (TKIs) prompted mitochondrial accumulation of pro-apoptotic BH3-only protein BIM, which sequestered MCL1 away from MULE-mediated degradation. A small-molecule combination screen uncovered that PI3K-mTOR pathway blockade prohibited MCL1 upregulation. Biochemical and immunocytochemical evidence indicated that mTOR complex 2 (mTORC2) bound and phosphorylated MCL1, facilitating its interaction with BIM. As a result, short-term polytherapy combining antineoplastic TKIs with PI3K, mTOR or MCL1 inhibitors sufficed to prevent DTP development and promote cancer eradication. Collectively, these findings support that upfront and transient targeting of BIM-dependent, mTORC2-regulated adaptive MCL1 preservation holds enormous promise to improve the therapeutic index of molecular targeted agents.

Comparison of Tongue Acupuncture and Traditional Acupuncture in the Treatment of Poststroke Dysarthria: A Meta-Analysis and Tongue Acupuncture System Classification Evaluation.

Objective: To discuss whether tongue acupuncture is more effective than traditional acupuncture in the treatment of poststroke dysarthria and explore the advantage of tongue acupuncture treatment parameters. Methods: We evaluated the efficacy of tongue acupuncture compared with traditional acupuncture through a rigorous meta-analysis process. The included studies were from eight databases in English and Chinese. The Cochrane risk of bias assessment tool was used to evaluate the quality of studies. Stata15.1 software was used for meta-analysis and sensitivity analysis. Tongue acupuncture therapeutic parameters were classified and counted based on tongue acupoint location, acupuncture manipulation, and the number of manipulations. Subgroup analysis was used to compare the differences between various treatment parameters. Outcome The meta-analysis eventually included a total of 9 studies. Tongue acupuncture is superior to traditional acupuncture in clinical efficacy [OR = 3.62, 95%Cl (2.24, 5.85), P < 0.0001], FDA score [SMD = -1.99, 95%Cl (-3.77, -0.21), P=0.028], and NIHSS score [WMD = 0.86, 95%Cl (0.15, 1.57), P=0.017, I2 = 31.7%] in the treatment of poststroke dysarthria. According to the classified statistics of tongue acupuncture treatment parameters, there are three kinds of tongue acupuncture points in 9 studies: lingual surface, sublingual, and both lingual surface and sublingual acupoints. The operation methods include the oblique stabbing of the root of the tongue, twisting after stabbing, and acupoint pricking. The number of operation methods varies from 1 to 3. Conclusion: Tongue acupuncture outperforms traditional acupuncture in terms of clinical efficacy, FDA score, and NIHSS score in the treatment of poststroke dysarthria. The curative effect of sublingual acupoints is better than that of lingual surface acupoints, the combined use of multiple manipulations is better than that of a single manipulation, and acupuncture manipulation has a cumulative effect. PROSPERO registration number: CRD42021285722.

Identification of Brachypodium distachyon B3 genes reveals that BdB3-54 regulates primary root growth.

B3 is a class of plant-specific transcription factors with important roles in plant development and growth. Here, we identified 69 B3 transcription factors in Brachypodium distachyon that were unevenly distributed across all five chromosomes. The ARF, REM, LAV, and RAV subfamilies were grouped based on sequence characteristics and phylogenetic relationships. The phylogenetically related members in the B3 family shared conserved domains and gene structures. Expression profiles showed that B3 genes were widely expressed in different tissues and varied in response to different abiotic stresses. BdB3-54 protein from the REM subfamily was located in the nucleus by subcellular localization and processed transcriptional activation activity. Overexpression of BdB3-54 in Arabidopsis increased primary root length. Our study provides a basis for further research on the functions of BdB3 genes.

Relationship between the Volume Ratio of Subchorionic Hematoma to Gestation SAC in First-trimester and Pregnancy Outcome of Patients with Threatened Abortion.

OBJECTIVE: To find the relationship between the volume ratio of subchorionic hematoma (SCH) to gestation sac measured by three-dimensional ultrasound and pregnancy outcome of patients with threatened abortion. STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: The Second Affiliated Hospital of Soochow University, Suzhou, China, from January 2016 to December 2020. METHODOLOGY: Medical data of patients, who were diagnosed with threatened abortion (persistent or intermittent vaginal bleeding) were collected. All included patients underwent ultrasonography for SCH at gestation age of 6-8 weeks. According to the patients' evaluation, they were classified into a case group combined with threatened abortion and SCH (n=145), and a control group with threatened abortion (n=76). The clinical data and three-dimensional ultrasound parameters of the two groups were compared to find the relationship between the volume ratio of SCH to gestation sac and pregnancy outcome. RESULTS: In the case group, the hospital stay was longer, the abdominal pain, its duration ≥7 days, and adverse pregnancy outcomes were higher than in the control group (p<0.05). Patients with moderate and severe area ratio and volume ratio of SCH to gestation sac were significantly related to higher abortion and stillbirth rates than patients with mild ratio (p<0.05). The area under the curve, sensitivity and specificity of the volume ratio of SCH to gestation sac in predicting abortion and stillbirth were higher than that of the area ratio of SCH to gestation sac. CONCLUSION: The volume ratio of SCH to gestation sac by three-dimensional ultrasound in first-trimester plays an important role to predict pregnancy outcome. KEY WORDS: Ultrasonography, Hematoma, Pregnancy outcome, Threatened abortion, ROC curve.

Management of the palato-radicular groove with a periodontal regenerative procedure and prosthodontic treatment: A case report.

BACKGROUND: Palato-radicular groove (PRG) is defined as an anomalous formation of teeth. The etiology of PRG remains unclear. The prognosis of a tooth with a PRG is unfavorable. The treatment of combined periodontal-endodontic lesions requires multidisciplinary management to control the progression of bone defects. Some researchers reported cases that had short-term observations. The management of teeth with PRGs is of great clinical significance. However, to date, no case reports have been documented on the use of bone regeneration and prosthodontic treatment for PRGs. CASE SUMMARY: This case reported the management of a 40-year-old male patient with the chief complaint of slight mobility and abscess in the upper right anterior tooth for 15 d and was diagnosed with type II PRG of tooth 12 with combined endodontic-periodontal lesions. The accumulation of plaque and calculus caused primary periodontitis and a secondary endodontic infection. A multidisciplinary management approach was designed that included root canal therapy, groove sealing, a periodontal regenerative procedure, and prosthodontic treatment. During a 2-year follow-up period, a good prognosis was observed. CONCLUSION: This report indicates that bone regeneration and prosthodontic treatment may contribute to the long-term favorable prognosis of teeth with PRGs.

Epithelial-Mesenchymal Transition Induces GSDME Transcriptional Activation for Inflammatory Pyroptosis.

GSDME is a newly recognized executor of cellular pyroptosis, and has been recently implicated in tumor growth and immunity. However, knowledge about the molecular regulators underlying GSDME abundance remains limited. Here, we performed integrative bioinformatics analyses and identified that epithelial-mesenchymal transition (EMT) gene signatures exhibited positive correlation with GSDME levels across human cancers. A causal role was supported by the observation that EMT dictated GSDME reversible upregulation in multiple experimental models. Mechanistically, transcriptional activation of GSDME was directly driven by core EMT-activating transcription factors ZEB1/2, which bound to the GSDME promoter region. Of functional importance, elevated GSDME in mesenchymally transdifferentiated derivatives underwent proteolytic cleavage upon antineoplastic drug exposure, leading to pyroptotic cell death and consequent cytokine release. Taken together, our findings pinpointed a key transcriptional machinery controlling GSDME expression and indicated potential therapeutic avenues to exploit GSDME-mediated inflammatory pyroptosis for the treatment of mesenchymal malignancies.

Identification of GATA Transcription Factors in Brachypodium distachyon and Functional Characterization of BdGATA13 in Drought Tolerance and Response to Gibberellins.

GATA transcription factors (TFs) are type IV zinc-finger proteins that have roles in plant development and growth. The 27 GATA TFs identified in the Brachypodium distachyon genome in this study were unevenly distributed across all five chromosomes and classified into four subgroups. Phylogenesis-related GATAs shared similar gene structures and conserved motifs. Expression profiles showed that all BdGATA genes were expressed in leaves and most were induced by PEG treatment. BdGATA13 was predominantly expressed in leaf tissue and phylogenetically close to OsSNFL1, AtGNC, and AtGNL. Its protein was detected in the nucleus by subcellular localization analysis. Overexpression of BdGATA13 in transgenic Arabidopsis resulted in darker green leaves, later flowering, and more importantly, enhanced drought tolerance compared to the wild type. BdGATA13 also promoted primary root development under GA treatment. These results lay a foundation for better understanding the function of GATA genes in B. distachyon and other plants.

Risk assessment of freezing injury during overwintering of wheat in the northern boundary of the Winter Wheat Region in China.

Freezing injury is one of the main restriction factors for winter wheat production, especially in the northern part of the Winter Wheat Region in China. It is very important to assess the risk of winter wheat-freezing injury. However, most of the existing climate models are complex and cannot be widely used. In this study, Zunhua which is located in the northern boundary of Winter Wheat Region in China is selected as research region, based on the winter meteorological data of Zunhua from 1956 to 2016, seven freezing disaster-causing factors related to freezing injury were extracted to formulated the freezing injury index (FII) of wheat. Referring to the historical wheat-freezing injury in Zunhua and combining with the cold resistance identification data of the National Winter Wheat Variety Regional Test (NWWVRT), consistency between the FII and the actual freezing injury situation was tested. Furthermore, the occurrence law of freezing injury in Zunhua during the past 60 years was analyzed by Morlet wavelet analyze, and the risk of freezing injury in the short term was evaluated. Results showed that the FII can reflect the occurrence of winter wheat-freezing injury in Zunhua to a certain extent and had a significant linear correlation with the dead tiller rate of wheat (P = 0.014). The interannual variation of the FII in Zunhua also showed a significant downward trend (R2 = 0.7412). There are two cycles of freezing injury in 60 years, and it showed that there's still exist a high risk in the short term. This study provides reference information for the rational use of meteorological data for winter wheat-freezing injury risk assessment.