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Abstract Reactive oxygen species (ROS)‐mediated sonodynamic therapy (SDT) holds increasing potential in treating deep‐seated tumor owing to the high tissue‐penetration depth. However, the inevitable accumulation of sonosensitizers in normal tissues not only make it difficult to realize the in situ SDT, but also induces sonodynamic effects in normal tissues. Herein, this work reports the passivation and selective activation strategies for the sonodynamic and near‐infrared (NIR) imaging performances of an intelligent antitumor theranostic platform termed Cu‐IR783 nanoparticles (NPs). Owing to the ruptured coordination bond between IR783 with Cu ions by responding to tumor microenvironment (TME), the selective activation of IR783 only occurred in tumor tissues to achieve the visualized in‐situ SDT. The tumor‐specific released Cu ions not only realized the cascade amplification of ROS generation through Cu+‐mediated Fenton‐like reaction, but also triggered cuproptosis through Cu+‐induced DLAT oligomerization and mitochondrial dysfunction. More importantly, the immunosuppressive TME can be reversed by the greatly enhanced ROS levels and high‐efficiency cuproptosis, ultimately inducing immunogenic cell death that promotes robust systemic immune responses for the eradication of primary tumors and suppression of distant tumors. This work provides a distinct paradigm of the integration of SDT, CDT, and cuproptosis in a controlled manner to achieve visualized in‐situ antitumor therapy.

ABSTRACT Over-application of chemical fertilizers and continuous cropping obstacles seriously restrict the sustainable development of tobacco production. Localized fertilization of beneficial microbes has potential advantages in achieving higher productivity, but the underlying biological mechanisms of interactions between rhizospheric microorganisms and the related metabolic cycle remain poorly characterized. Here, an integrative analysis of microbiomes with non-targeted metabolomics was performed on 30 soil samples of rhizosphere, root surrounding, and bulk soils from flue‐cured tobacco under continuous and non-continuous monocropping systems. The analysis was conducted using UPLC-MS/MS platforms and high-throughput amplicon sequencing targeting the bacterial 16S rRNA gene and fungal ITS gene. The microbial inoculant consisted of Bacillus subtilis, B. velezensis, and B. licheniformis at the ratio of 1:1:1 in effective microbial counts, improved the cured leaf yield and disease resistance of tobacco, and enhanced nicotine and nitrogen contents of tobacco leaves. The bacterial taxa Rhizobium, Pseudomonas, Sphingomonadaceae, and Burkholderiaceae of the phylum Proteobacteria accumulated in high relative abundance and were identified as biomarkers following the application of the microbial inoculant. Under continuous monocropping, metabolomics demonstrated that the application of the microbial inoculant significantly affected the soil metabolite spectrum, and the differential metabolites were significantly enriched to the synthesis and degradation of nicotine (nicotinate and nicotinamide metabolism and biosynthesis of alkaloids derived from nicotinic acid). In addition, microbes were closely related to the accumulation of metabolites through correlation analysis. The interactions between plant roots and rhizospheric microorganisms provide valuable information for understanding how these beneficial microbes affect complex biological processes and the adaption capacity of plants to environments.IMPORTANCEThis study elaborated on how the microbial fertilizer significantly changed overall community structures and metabolite spectrum of rhizospheric microbes, which provide insights into the process of rhizosphere microbial remolding in response to continuous monocropping. we verified the hypothesis that the application of the microbial inoculant in continuous cropping would lead to the selection of distinct microbiota communities by establishing models to correlate biomarkers. Through correlation analysis of the microbiome and metabolome, we proved that rhizospheric microbes were closely related to the accumulation of metabolites, including the synthesis and degradation of nicotine. The interactions between plant roots and rhizospheric microorganisms provide valuable information for understanding how these beneficial microbes affect complex biological processes and the adaption capacity of plants to environments.

Abstract To accelerate the pace in the field of photothermal therapy (PTT), it is urged to develop easily accessible photothermal agents (PTAs) showing high photothermal conversion efficiency (PCE). As a proof‐of‐concept, hereby a conventional strategy is presented to prepare donor–acceptor (D–A) structured PTAs through cycloaddition‐retroelectrocyclization (CA–RE) reaction, and the resultant PTAs give high PCE upon near‐infrared (NIR) irradiation. By joint experimental‐theoretical study, these PTAs exhibit prominent D–A structure with strong intramolecular charge transfer (ICT) characteristics and significantly twisting between D and A units which account for the high PCEs. Among them, the DMA‐TCNQ exhibits the strongest absorption in NIR range as well as the highest PCE of 91.3% upon irradiation by 760‐nm LED lamp (1.2 W cm−2). In vitro and in vivo experimental results revealed that DMA‐TCNQ exhibits low dark toxicity and high phototoxicity after IR irradiation along with nude mice tumor inhibition up to 81.0% through intravenous therapy. The findings demonstrate CA–RE reaction as a convenient approach to obtain twisted D–A structured PTAs for effective PTT and probably promote the progress of cancer therapies.

Aerodynamic modeling and control law design methods are crucial foundational technologies that enable efficient maneuvering flight of aircraft. Hence, this study focuses on how to construct the aerodynamic model and design control law using machine learning, as well as their differences from classical methods. To conduct this, a modified NACA0012 airfoil with a tail functioning as an elevator is employed as the geometry model. Through the utilization of the rigid dynamic grid method and overlapping grid technology, the pitch of the airfoil and the deflection of the elevator are efficient to execute. Firstly, the pitching moment coefficient is sampled through both steady and unsteady computations. Then, multivariate nonlinear regression (MNR) models and artificial neural network (ANN) models are established based on steady and unsteady sampling data, respectively. Additionally, the obtained model is evaluated using open-loop control laws. Based on the evaluation, the proportional-integral-derivative (PID) control algorithm is used to design the airfoil pitching control law using the MNR model. Meanwhile, deep reinforcement learning (DRL) is used to design the pitching control law using the ANN model. Finally, the PID and DRL controllers are implemented in a CFD environment for airfoil pitching control to verify their effectiveness in application scenarios. The results suggest that models based on both steady and unsteady data can reflect dynamic aerodynamic characteristics. However, using unsteady computation for data sampling significantly reduces time consumption compared to steady computation. Furthermore, the model constructed by ANN may have unexpected excellent characteristics. Both the PID and DRL control laws, designed based on the models, perfectly complete the control process in the CFD environment. This study provides valuable insights for the implementation of controllable maneuvering flight in aircraft.

Abstract Albeit nanozymes‐based tumor catalytic therapy (NCT) relies on endogenous chemical reactions that could achieve tumor microenvironment (TME)‐specialized reactive oxygen species (ROS) production, the unsatisfactory catalytic activity of nanozymes accompanied by complex TME poses a barrier to the therapeutic effect of NCT. Herein, a one‐step in situ synthesis strategy is reported to construct ternary Ru/TiO2−x@TiCN heterojunctions through oxidative conversion of TiCN nanosheets (NSs) to TiO2−x NSs and reductive deposition of Ru3+ to Ru nanoparticles. The narrow bandgap and existence of heterojunctions enhance the ultrasound‐activated ROS generation of Ru/TiO2−x@TiCN because of the accelerated electron transfer and inhibits electron–hole pair recombination. The augmented ROS production efficiency is achieved by Ru/TiO2−x@TiCN with triple enzyme‐like activities, which amplifies the ROS levels in a cascade manner through the catalytic decomposition of endogenous H2O2 to relieve hypoxia and heterojunction‐mediated NCT, as well as depletion of overexpressed glutathione. The satisfactory therapeutic effects of Ru/TiO2−x@TiCN heterojunctions are achieved through synergetic sonodynamic therapy and NCT, which achieve the complete elimination of tumors without recurrence. This strategy highlights the potential of in situ synthesis of semiconductor heterojunctions as enhanced sonosensitizers and nanozymes for efficient tumor therapy.

Felodipine (FEL)–tetracyanoethylene (TCNE)–2,2′-bipyridine (Bpy) complex was prepared with FEL, TCNE–Bpy and characterized by fluorescence, ultraviolet, and infrared. By exploring the concentration and dosage of Bpy, it was found that 1 mL 2 × 10−3 mol‧L−1 of Bpy had the best effect. The sequence of reagent addition was determined to be followed by FEL, then by TCNE, and then followed by Bpy. The concentration of FEL was 2.5 × 10−4 to 9.0 × 10−3 mol‧L−1, which had a good linear relationship with fluorescence intensity. The compound had good accuracy, precision, and specificity, and could be used for the determination of phelodipine content in FEL sustained-release tablets.

Background/ObjectiveSilage characteristics of grass materials directly affect their silage qualities. To expand the source of silage raw materials and develop mixed silages underlined by exploring the positive interactions between forage grasses and legumes, three gramineous grasses, Napier grass (Pennisetum purpureum), king grass (Pennisetum sinese), and forage maize (Zea mays) were separately mixed ensiled with a combination of four forage legumes including Medicago sativa, Vicia villosa, Vicia sativa, and Trifolium repens.MethodsThe chemical composition and fermentation quality of the mixed silages were analyzed and compared with those of the sole silages of these three grasses, as well as the diversity of microbial communities, through the 16S/ITS full-length sequencing.ResultsThe results showed that the inclusion of forage legumes could somewhat improve the fermentation quality, as indicated by significantly (p < 0.05) higher crude protein and lactic acid contents while lower neutral detergent fiber, acid detergent fiber contents and pH values, compared with the sole silages. Among the three types of mixed silages, the mixed king grass had the highest dry matter and crude protein content as well as lowest neutral detergent fiber and acid detergent fiber content. Meanwhile, the bacterial and fungal communities in the mixed silages were influenced by increased the relative abundance of lactic acid bacteria, which inhibited the proliferation of undesirable bacteria, such as Hafnia alvei, Enterobacter cloacae, and Serratia proteamaculanss. Co-occurrence networks identified 32 nodes with 164 positive and 18 negative correlations in bacteria and 80 nodes with two negative and 76 positive correlations in fungi during fermentation.ConclusionInclusion of forage legume to grasses can improve the fermentation quality and optimize the structure of microbial community, which appears to be a feasible strategy to enhance the forage resource utilization.

Multi-walled carbon nanotubes (MWCNTs) mainly induce oxidative stress through the overproduction of reactive oxygen species (ROS), which can lead to cytotoxicity. Celastrol, a plant-derived compound, can exert antioxidant effects by reducing ROS production. Our results indicated that exposure to MWCNTs decreased cell viability and increased ROS production. Nrf2 knockdown (kd) led to increased ROS production and enhanced MWCNT-induced cytotoxicity. Keap1-kd led to decreased ROS production and attenuated cytotoxicity. Treatment with celastrol significantly decreased ROS production and promoted Keap1 protein degradation through the lysosomal pathway, thereby enhancing the translocation of Nrf2 from the cytoplasm to the nucleus and increasing HO-1 expression. The in vivo results showed that celastrol could alleviate the inflammatory damage of lung tissues, increase the levels of the antioxidants, GSH and SOD, as well as promote the expression of the antioxidant protein, HO-1 in MWCNT-treated mice. Celastrol can alleviate MWCNT-induced oxidative stress through the Keap1/Nrf2/HO-1 signaling pathway.

Graphite-carbon nitride (g-C3N4) was prepared by thermocondensation, and g-C3N4/BiVO4 material (GCB) and g-C3N4/CNTs composite material (GCC) were prepared by doping different contents of BiVO4 and carbon nanotubes (CNTs) with g-C3N4 samples, respectively. Then, BiVO4, CNTs, and g-C3N4 samples with different contents were doped to prepare ternary composite material (GCBC). In the performance experiment, Sulfamethoxazole (SMZ) was used as degradation material to evaluate the photocatalytic performance of the prepared samples, and the degradation reaction kinetics equation, quadric cycle stability experiment, free radical capture, and intermediates identification were studied. The intermediates of photocatalytic degradation of SMZ were analyzed by high-performance liquid chromatography-mass spectrometry. From the experimental data, it can be seen that for SMZ solution, when the reaction time T = 0 min and retention time rt = 7.53 min, there is a peak corresponding to the substance with m/z [M + H]+ of 254, which is judged as SMZ. At 20, 40, and 60 min, rt was 2.00, 7.06, and 9.57 min, indicating the presence of intermediates in the photocatalytic process. Experimental analysis shows that there are three intermediates of SMZ degradation by composite sample GCBC. In this work, three kinds of composite materials were successfully prepared, and a variety of characterization, SMZ as pollutants, test the photocatalytic performance of composite materials (GCB, GCC, and GCBC) samples, and elucidated the cyclic stability of the material, active species capture, and photocatalytic degradation mechanism.

Synchytrium endobioticum, the causal agent of potato wart disease, poses a major threat to commercial potato production. Understanding the roles of transcriptionally regulated genes following pathogen infection is necessary for understanding the system-level host response to pathogen. Although some understanding of defense mechanisms against S. endobioticum infection has been gained for incompatible interactions, the genes and signaling pathways involved in the compatible interaction remain unclear. Based on the collection of wart diseased tubers of a susceptible cultivar, we performed phenotypic and dual RNA-Seq analyses of wart lesions in seven stages of disease progression. We totally detected 5,052 differentially expressed genes (DEGs) by comparing the different stages of infection to uninfected controls. The tendency toward differential gene expression was active rather than suppressed under attack by the pathogen. The number of DEGs step-up along with the development of the disease and the first, third and seventh of the disease stages showed substantially increase of DEGs in comparison of the previous stage. The important functional groups identified via Gene ontology (GO) and KEGG enrichment were those responsible for plant-pathogen interaction, fatty acid elongation and phenylpropanoid biosynthesis. Gene coexpression networks, composed of 17 distinct gene modules that contained between 25 and 813 genes, revealed high interconnectivity of the induced response and led to the identification of a number of hub genes enriched at different stages of infection. These results provide a comprehensive perspective on the global response of potato to S. endobioticum infection and identify a potential transcriptional regulatory network underlying this susceptible response, which contribute to a better understanding of the potato–S. endobioticum pathosystem.

Viral disease in potatoes has been a major problem in potato production worldwide. In addition to the potential risk of introducing new diseases in new areas, viral-disease epidemics/pandemics can be initiated by “spillover” of indigenous viruses from infected alternative hosts into introduced cultivars. To investigate the tendency of potential viral infection/resistance, we analyzed the viromes of introduced and indigenous varieties of potatoes among different tissues using RNA-seq libraries. Bioinformatics analyses revealed that potato viruses PVM, PVY, and PVS were dominant and the most frequently identified viruses infecting potato virus-free plants in the field, and showed an infection bias between introduced and indigenous cultivars. PVY and PVS were the major viruses in introduced varieties, whereas PVM showed an extraordinarily high percentage in the indigenous variety. Other three common viruses, PVH, potato mop-top virus, and potato leafroll virus were identified specifically in the indigenous variety. There was a tendency for tissue-specific infection and sequence variation in viruses: underground parts (tubers, roots) harbored more unusual viruses, and tubers harbored relatively more variation with a high frequency of single nucleotide polymorphisms than other tissues. Taken together, our study provides a comprehensive overview of the composition, distribution, and sequence variation of viruses between introduced and indigenous varieties of potatoes.

Abstract Background The circadian clock drives endogenous 24-h rhythms that allow organisms to adapt and prepare for predictable and repeated changes in their environment throughout the day-night (diurnal) cycle. Many components of the circadian clock in Arabidopsis thaliana have been functionally characterized, but comparatively little is known about circadian clocks in grass species including major crops like maize and sorghum. Results Comparative research based on protein homology and diurnal gene expression patterns suggests the function of some predicted clock components in grasses is conserved with their Arabidopsis counterparts, while others have diverged in function. Our analysis of diurnal gene expression in three panicoid grasses sorghum, maize, and foxtail millet revealed conserved and divergent evolution of expression for core circadian clock genes and for the overall transcriptome. We find that several classes of core circadian clock genes in these grasses differ in copy number compared to Arabidopsis, but mostly exhibit conservation of both protein sequence and diurnal expression pattern with the notable exception of maize paralogous genes. We predict conserved cis-regulatory motifs shared between maize, sorghum, and foxtail millet through identification of diurnal co-expression clusters for a subset of 27,196 orthologous syntenic genes. In this analysis, a Cochran–Mantel–Haenszel based method to control for background variation identified significant enrichment for both expected and novel 6–8 nucleotide motifs in the promoter regions of genes with shared diurnal regulation predicted to function in common physiological activities. Conclusions This study illustrates the divergence and conservation of circadian clocks and diurnal regulatory networks across syntenic orthologous genes in panacoid grass species. Further, conserved local regulatory sequences contribute to the architecture of these diurnal regulatory networks that produce conserved patterns of diurnal gene expression.

Rice florets are subtended by two sterile lemmas, whose origin and biological functions have not been studied extensively. Here we demonstrate that two putative transcription factors, LAX PANICLE1 (LAX1) and FRIZZY PANICLE (FZP), synergistically control the development of sterile lemmas. Both LAX1 and FZP are previously known for their roles in panicle and floret development. Disruption of either LAX1 or FZP greatly reduces the number of floret development. We generated new lax1 mutants (lax1-c) using CRISPR/Cas9 gene editing technology. In addition to the expected lax panicle phenotypes, we noticed that a significant number of spikelets of lax1-c developed elongated sterile lemmas. Moreover, our characterization of lax1-RNAi plants also revealed sterile lemma phenotypes similar to lax1-c mutants. We isolated a weak allele of fzp (fzp-14) in a genetic screen for lax1–1 enhancers. The fzp-14 lax1–1 double mutants completely eliminated flower development. Interestingly, the isolated fzp-14 produced spikelets with elongated sterile lemmas. Furthermore, fzp-14 was haploid-insufficient in the lax1–1 background whereas fzp-14 heterozygous plants were indistinguishable from wild type plants. The lax1–1 fzp-14+/− also developed elongated sterile lemma as observed in lax1-c, lax1-RNAi, and fzp-14, suggesting that LAX1 and FZP synergistically control sterile lemma development. Keywords: LAX1, FZP, Rice, CRISPR, Flower development, Sterile lemma

Background: Dietary fat absorption involves the re-esterification of digested triacylglycerol in the enterocytes, it is a biological process catalyzed by monoacylglycerol O-acyltransferase 2 (MOGAT2, aka MGAT2), which is highly expressed in the small intestine. A previous study showed that the loss of the Mogat2 gene can prevent high-fat diet-induced obesity in mice. Obesity is associated with an increased risk of several types of cancer including a postmenopausal mammary tumor. Methods: We collected 147 patients with triple-negative breast adenocarcinoma to explore the relationship between MOGAT2 expression and overall patient survival. The TCGA data were also retrieved for analyzing the prognostic values of MOGAT2 mRNA level as well as the relationships between MOGAT2 and DGAT1/2 mRNA levels. We also used a Mogat2-deficient mouse mammary tumor model by crossing Mogat2-deficient mice with MMTV-PyMT mice to examine the effect of MOGAT2 on mammary tumor development. Results: In human triple-negative breast adenocarcinoma, elevated expression of MOGAT2 correlated with a poorer patient prognosis. Obesity could be induced by a relatively high-fat diet (37% of calories from fat) in the mice with or without Mogat2 knockout. Mammary tumor development was deteriorated by a relatively high-fat diet regardless of Mogat2 deficiency. As a compensation mechanism, upregulation of diacylglycerol O-acyltransferases 1 and 2 (Dgat1 and Dgat2) in the Mogat2 deficient mice was found. Consistently, in human normal tissues adjacent to breast cancer, an inverse correlation between MOGAT2 mRNA level and DGAT1/2 mRNA levels was also found. Conclusions: Elevated expression of MOGAT2 in triple-negative breast adenocarcinoma predicts poorer patient overall survival. With the compensation of Dgat1 and Dgat2, Mogat2 deficiency alone cannot prevent fat diet-induced obesity, nor prevent mammary tumor development in a mouse model.

Angelica dahurica is a famous functional food and herb. To guarantee quality of A. dahurica, a strategy “Q-markers targeted screening” was successfully developed by sufficient extraction of compounds and the targeted screening of qualitative and quantitative markers calculated through chemometric methods based fingerprints. Accelerated solvent extraction was selected due to its prominent advantages exhibiting the maximum extraction yields and varieties of compounds and especially excellent reproducibility (RSD

Psoriasis is characterized by keratinocyte proliferation and immune cell infiltration. M2 isoform of pyruvate kinase (PKM2) was reported to have an important role in cell proliferation, which is a rate-limiting enzyme that regulates the final step of glycolysis. However, how PKM2 regulates cell metabolism and proliferation in psoriatic keratinocytes is still poorly understood. Interestingly, we found that PKM2 was highly expressed in psoriatic epidermis from patients and mouse models. PKM2 overexpression promoted keratinocyte glycolytic metabolism while knockdown inhibited keratinocyte proliferation and glycolysis. Mice lacking PKM2 specifically in keratinocytes, pharmacological inhibition of PKM2 or glycolysis inhibited keratinocyte proliferation and showed obvious remission in an imiquimod-induced psoriatic mouse model. Moreover, the inhibitor of the EGF-receptor blocked EGF-stimulated PKM2 expression and glycolysis in keratinocytes. We identify PKM2 as an upregulated gene in psoriasis. PKM2 is essential in keratinocyte over-proliferation and may represent a therapeutic target for psoriasis.

Mesocentrotus nudus is an important commercially aquatic species because of its high edible and medicinal values. However, wild stocks have dramatically decreased in recent decades. Understanding the population structure and genetic diversity can provide vital information for genetic conservation and improvement. In the present study, the genotyping-by-sequencing (GBS) approach was adopted to identify the genome-wide single-nucleotide polymorphisms (SNPs) from a collection of 80 individuals consisting of five geographical populations (16 individuals from each population), covering the natural habitats of M. nudus in China seas. An average of 0.96-Gb clean reads per sample were sequenced, and a total of 51,738 biallelic SNPs were identified. Based on these SNPs, diversity index analysis showed that all populations have a similar pattern with positive Fis (0.136) and low Ne (724.3). Low genetic differentiation and high genetic connectivity among five geographical populations were detected by pairwise Fst, principal component analysis (PCA), admixture, and phylogenetic analysis. Besides, two YWL individuals originating from an isolated ancestor may imply that there is a genetically differentiated population in the adjacent sea. Overall, the results showed that GBS is an effective method to detect genome-wide SNPs for M. nudus and suggested that the protective measures and the investigation with larger spatial scale and sample size for M. nudus should be carried out in the future.

AbstractGenetic diversity is the raw material for germplasm enhancement. Landraces and wild species relatives of potato, which contain a rich gene pool of valuable agronomic traits, can provide insights into the genetic diversity behind the adaptability of the common potato. The diploid plant, Solanum stenotomum

Long-term continuous monocropping negatively influences the physicochemical and biological characteristics of cultivated soil, especially for the economically important crop of flue-cured tobacco that is intolerant to continuous monocropping. The underlying mechanism of soil sickness under continuous monoculture and the temporal dynamic changes over the tobacco life cycle among different monoculture time spans remain poorly characterized. In this study, high-throughput sequencing targeting the 16S rRNA gene phylogenetic marker was performed on 60 soil samples of rhizosphere soil from flue−cured tobacco in the replanting, growth and harvest period across 5, 10, and 20 years of a continuous monocropping system. Bacterial community diversity decreased with the increase in duration of continuous monocropping, and the rhizosphere microbiota was highly dynamic in the harvest period. The random forests algorithm identified 17 taxa as biomarkers and a model was established to correlate root microbiota with continuous monocropping time of flue-cured tobacco. Molecular ecological network analysis elaborated the differences and interactions in bacterial co-occurrence patterns under different monocropping systems. The co-occurrence microbial network was larger in size but there were fewer interactions among microbial communities with the increase in continuous monocropping duration. These results provide insights into the changes of flue−cured tobacco root microbiome diversity in response to continuous monocropping and suggest a model for successional dynamics of the root-associated microbiota over continuous monocropping time and development stage. This study may help elucidate the theoretical basis underlying obstacles to continuous monocropping and could contribute to improving guidance for tobacco production.

CRISPR/Cas9 gene editing technology has been very effective in editing genes in many plant species including rice. Here we further improve the current CRISPR/Cas9 gene editing technology in both efficiency and time needed for isolation of transgene-free and target gene-edited plants. We coupled the CRISPR/Cas9 cassette with a unit that activates anthocyanin biosynthesis, providing a visible marker for detecting the presence of transgenes. The anthocyanin-marker assisted CRISPR (AAC) technology enables us to identify transgenic events even at calli stage, to select transformants with elevated Cas9 expression, and to identify transgene-free plants in the field. We used the AAC technology to edit LAZY1 and G1 and successfully generated many transgene-free and target gene-edited plants at T1 generation. The AAC technology greatly reduced the labor, time, and costs needed for editing target genes in rice.

Added risk portended by diabetes in addition to hypertension has been related to an amplification of endothelial dysfunction. β-blockers are widely used for cardiovascular diseases and improve the endothelial function compared with a placebo. However, the effect of β-blockers on the endothelial progenitor cells (EPCs) function in diabetes is still unknown. Five β-blockers (metoprolol, atenolol, propranolol, bisoprolol, and nebivolol) were tested in EPC functional screening. Metoprolol improved EPC function significantly among the five β-blockers and was chosen for the in vivo tests in STZ induced diabetic mice. Reactive hyperemia peripheral arterial tonometry (RH-PAT) measurements were performed using the Endo-PAT2000 device in diabetic patients. Metoprolol, but not other β-blockers, improved EPC function in both tube formation and migration assay. EPC function was significantly decreased in diabetic mice, and metoprolol treatment restored damaged EPC migration capabilities and circulation EPC number. Metoprolol treatment promoted wound healing and stimulated angiogenesis in diabetic mice. Furthermore, metoprolol significantly enhanced eNOS phosphorylation and decreased O2− levels in EPCs of diabetic mice. In clinical trials, the RH-PAT index was significantly higher in metoprolol-treated versus bisoprolol-treated diabetics. Metoprolol could accelerate wound healing in diabetic mice and improve endothelial function in diabetic subjects, which may be mediated in part by improving impaired EPC function.

A well-developed root system in rice and other crops can ensure plants to efficiently absorb nutrients and water. Auxin is a key regulator for various aspect of root development, but the detailed molecular mechanisms by which auxin controls crown root development in rice are not understood. We show that overexpression of a YUC gene, which encodes the rate-limiting enzyme in auxin biosynthesis, causes massive proliferation of crown roots. On the other hand, we find that disruption of TAA1, which functions upstream of YUC genes, greatly reduces crown root development. We find that YUC overexpression-induced crown root proliferation requires the presence of the transcription factor WOX11. Moreover, the crown rootless phenotype of taa1 mutants was partially rescued by overexpression of WOX11. Furthermore, we show that WOX11 expression is induced in OsYUC1 overexpression lines, but is repressed in the taa1 mutants. Our results indicate that auxin synthesized by the TAA/YUC pathway is necessary and sufficient for crown root development in rice. Auxin activates WOX11 transcription, which subsequently drives crown root initiation and development, establishing the YUC-Auxin-WOX11 module for crown root development in rice.

Objectives: A novel analysis was undertaken to select a significant ultrasonographic parameter (USP) for classifying fetuses to support artificial neural network (ANN), and thus to enhance the accuracy of fetal weight estimation. Methods: In total, 2127 singletons were examined by prenatal ultrasound within 3 days before delivery. First, correlation analysis was used to determine a significant USP for fetal grouping. Second, K-means algorithm was utilized for fetal size classification based on the selected USP. Finally, stepwise regression analysis was used to examine input parameters of the ANN model. Results: The estimated fetal weight (EFW) of the new model showed mean absolute percent error (MAPE) of 5.26 ± 4.14% and mean absolute error (MAE) of 157.91 ± 119.90 g. Comparison of EFW accuracy showed that the new model significantly outperformed the commonly-used EFW formulas (all p < 0.05). Conclusion: We proved the importance of choosing a specific grouping parameter for ANN to improve EFW accuracy.