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expression analysis and was validated by haplotype analysis of 330 accessions with high-depth (10×) resequencing data (unpublished).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.

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.

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.

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.

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.

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.

Ecological genomics of Chinese wheat improvement: implications in breeding for adaptation.

BACKGROUND: China has diverse wheat varieties that adapt to very different environments divided into ten agro-ecological zones. A better understanding of genomic differences and patterns of selection among agro-ecological zones could provide useful information in selection of specific adaptive traits in breeding. RESULTS: We genotyped 438 wheat accessions from ten zones with kompetitive allele specific PCR (KASP) markers specific to 47 cloned genes for grain yield, quality, adaptation and stress resistance. Phylogenetic trees and principle component analysis revealed clear differences in winter and spring growth habits. Nucleotide diversity (π) and π ratio (πCL/πMCC) suggested that genetic diversity had increased during breeding, and that Chinese landraces (CL) from Zones I-V contributed little to modern Chinese cultivars (MCC). π ratio and Fst identified 24 KASP markers with 53 strong selection signals specific to Zones I (9 signals), II (12), III (5), IV (5), V (6), and VI (6). Genes with clear genetic differentiation and strong response to selection in at least three zones were leaf rust resistance gene Lr34 (I, II, III and IV), photoperiod sensitivity gene Ppd-D1 (I, II, III, IV and V), vernalization gene Vrn-B1 (V, VII, VIII and X), quality-related gene Glu-B1 (I, II and III) and yield-related genes Sus1-7B (I, II, III, IV and IX), Sus2-2A (I, II, III., IV and VI) and GW2-6B (II, V and VI). CONCLUSIONS: This study examined selection of multiple genes in each zone, traced the distribution of important genetic variations and provided useful information for ecological genomics and enlightening future breeding goals for different agro-ecological zones.

Identification and evolution of C4 photosynthetic pathway genes in plants.

BACKGROUND: NADP-malic enzyme (NAPD-ME), and pyruvate orthophosphate dikinase (PPDK) are important enzymes that participate in C4 photosynthesis. However, the evolutionary history and forces driving evolution of these genes in C4 plants are not completely understood. RESULTS: We identified 162 NADP-ME and 35 PPDK genes in 25 species and constructed respective phylogenetic trees. We classified NADP-ME genes into four branches, A1, A2, B1 and B2, whereas PPDK was classified into two branches in which monocots were in branch I and dicots were in branch II. Analyses of selective pressure on the NAPD-ME and PPDK gene families identified four positively selected sites, including 94H and 196H in the a5 branch of NADP-ME, and 95A and 559E in the e branch of PPDK at posterior probability thresholds of 95%. The positively selected sites were located in the helix and sheet regions. Quantitative RT-PCR (qRT-PCR) analyses revealed that expression levels of 6 NADP-ME and 2 PPDK genes from foxtail millet were up-regulated after exposure to light. CONCLUSION: This study revealed that positively selected sites of NADP-ME and PPDK evolution in C4 plants. It provides information on the classification and positive selection of plant NADP-ME and PPDK genes, and the results should be useful in further research on the evolutionary history of C4 plants.

Accurate and efficient estimation of small P-values with the cross-entropy method: applications in genomic data analysis.

MOTIVATION: Small P-values are often required to be accurately estimated in large-scale genomic studies for the adjustment of multiple hypothesis tests and the ranking of genomic features based on their statistical significance. For those complicated test statistics whose cumulative distribution functions are analytically intractable, existing methods usually do not work well with small P-values due to lack of accuracy or computational restrictions. We propose a general approach for accurately and efficiently estimating small P-values for a broad range of complicated test statistics based on the principle of the cross-entropy method and Markov chain Monte Carlo sampling techniques. RESULTS: We evaluate the performance of the proposed algorithm through simulations and demonstrate its application to three real-world examples in genomic studies. The results show that our approach can accurately evaluate small to extremely small P-values (e.g. 10-6 to 10-100). The proposed algorithm is helpful for the improvement of some existing test procedures and the development of new test procedures in genomic studies. AVAILABILITY AND IMPLEMENTATION: R programs for implementing the algorithm and reproducing the results are available at: https://github.com/shilab2017/MCMC-CE-codes. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Association of yield-related traits in founder genotypes and derivatives of common wheat (Triticum aestivum L.).

BACKGROUND: Yield improvement is an ever-important objective of wheat breeding. Studying and understanding the phenotypes and genotypes of yield-related traits has potential for genetic improvement of crops. RESULTS: The genotypes of 215 wheat cultivars including 11 founder parents and 106 derivatives were analyzed by the 9 K wheat SNP iSelect assay. A total of 4138 polymorphic single nucleotide polymorphism (SNP) loci were detected on 21 chromosomes, of which 3792 were mapped to single chromosome locations. All genotypes were phenotyped for six yield-related traits including plant height (PH), spike length (SL), spikelet number per spike (SNPS), kernel number per spike (KNPS), kernel weight per spike (KWPS), and thousand kernel weight (TKW) in six irrigated environments. Genome-wide association analysis detected 117 significant associations of 76 SNPs on 15 chromosomes with phenotypic explanation rates (R 2 ) ranging from 2.03 to 12.76%. In comparing allelic variation between founder parents and their derivatives (106) and other cultivars (98) using the 76 associated SNPs, we found that the region 116.0-133.2 cM on chromosome 5A in founder parents and derivatives carried alleles positively influencing kernel weight per spike (KWPS), rarely found in other cultivars. CONCLUSION: The identified favorable alleles could mark important chromosome regions in derivatives that were inherited from founder parents. Our results unravel the genetic of yield in founder genotypes, and provide tools for marker-assisted selection for yield improvement.

Numerical simulation of embryo transfer: how the viscosity of transferred medium affects the transport of embryos.

BACKGROUND: Embryo transfer (ET) is a key step of assisted reproductive procedures, where the transferred medium containing the embryos is injected into the uterine cavity through a transcervical catheter and blended with intrauterine fluid in the uterine cavity. This procedure determines the delivery sites of embryos in the uterine cavity and has crucial impact on the implantation. Due to practical restrictions and ethical issues, it is often difficult to perform an in vivo study in humans to examine factors that affect the motions and delivery of embryos during ET. Alternatively, mathematical modeling is a powerful tool to that end. RESULTS: A computational model is developed to simulate the intrauterine mixing flow and track the embryo motions. Two important factors affecting the intrauterine flow are studied via this model: the viscosity of the transferred medium and the injection speed. Numerical results show that the dispersion pattern and the final delivery sites of the embryos are significantly influenced by the viscosity of the transferred medium. Specially, increasing the transferred medium viscosity close to that of the uterine fluid can enhance the probability that the embryos are delivered close to the fundus and keep them from being dragged backward to the cervix during catheter withdrawal. In addition, a slow injection speed can lower the driving force on the embryo during ET, which can prevent the embryo from being injured. CONCLUSIONS: Based on our study, the practice of using a transferred medium with similar viscosity to that of the uterine fluid and a slow injection speed is recommended for real embryo transfer procedures in clinic.

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.

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.

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.

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.

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.

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.

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.

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.

Curcumin promotes osteogenic differentiation of human periodontal ligament stem cells by inducting EGR1 expression.

OBJECTIVE: Human periodontal ligament stem cells (hPDLSCs) attract attention for the periodontal regeneration therapy. Curcumin may promote osteogenic differentiation of hPDLSCs. This research aims to elucidate whether Curcumin displays promoting osteogenic differentiation and its mechanism. METHODS: The hPDLSCs were isolated from human periodontal ligament by immunomagnetic beads, identified with immumofluorescence. hPDLSCs were treated with 0, 5, 10, 20, 50, 100 µmol/L Curcumin. The early growth response gene 1 (EGR1) siRNA or plasmind were tranfected into the hPDLSCs. The viability, Alkaline Phosphatase (ALP) activity and mineralizaiton level of hPDLSCs were measured with 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay, ALP Assay Kit or Alizarin Red staining. The expression of EGR1, RUNX family transcription factor 2 (Runx2), bone gamma-carboxyglutamate protein (OC), secreted phosphoprotein 1 (OPN) and collagen type I alpha 1 chain (Collagen I), in hPDLSC were determined by Western blotting and quantitative reverse transcription-polymerase chain reaction. RESULTS: The isolated hPDLSCs were spindle or irregular, arranged in radial shape and shown positive expression of STRO-1, CD146 and Vimentin. Curcumin 10 µmol/L treatment maximal promoting the cells viability, ALP activities, mineralization, and levels of Runx2, OC, OPN, Collagen I and EGR-1 in hPDLSCs. EGR-1 siRNA transfection inversed Curcumin's promoting effect on ALP activities, mineralization, and levels of Runx2, OC, OPN, Collagen I and EGR-1 in hPDLSCs. While the EGR-1 plasmid transfection enhanced Curcumin's promoting effect on these parameters of hPDLSCs. CONCLUSION: Curcumin promotes the osteogenic differentiation of hPDLSCs, which may work through the EGR1. Curcumin may be a promising medicine for periodontitis treatment and periodontal regeneration.