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Tomato (Solanum lycopersicum) is an important crop but frequently experiences saline-alkali stress. Our previous studies have shown that exogenous spermidine (Spd) could significantly enhance the saline-alkali resistance of tomato seedlings, in which a high concentration of Spd and jasmonic acid (JA) exerted important roles. However, the mechanism of Spd and JA accumulation remains unclear. Herein, SlWRKY42, a Group II WRKY transcription factor, was identified in response to saline-alkali stress. Overexpression of SlWRKY42 improved tomato saline-alkali tolerance. Meanwhile, SlWRKY42 knockout mutants, exhibited an opposite phenotype. RNA-sequencing data also indicated that SlWRKY42 regulated the expression of genes involved in JA signaling and Spd synthesis under saline-alkali stress. SlWRKY42 is directly bound to the promoters of SlSPDS2 and SlNHX4 to promote Spd accumulation and ionic balance, respectively. SlWRKY42 interacted with SlMYC2. Importantly, SlMYC2 is also bound to the promoter of SlSPDS2 to promote Spd accumulation and positively regulated saline-alkali tolerance. Furthermore, the interaction of SlMYC2 with SlWRKY42 boosted SlWRKY42's transcriptional activity on SlSPDS2, ultimately enhancing the tomato's saline-alkali tolerance. Overall, our findings indicated that SlWRKY42 and SlMYC2 promoted saline-alkali tolerance by the Spd biosynthesis pathway. Thus, this provides new insight into the mechanisms of plant saline-alkali tolerance responses triggered by polyamines (PAs)., (© 2025 Institute of Botany, Chinese Academy of Sciences.)

Salt stress adversely affects the growth and yield of crops. Glutathione S-transferases (GSTs) are involved in plant growth and responses to biotic and abiotic stresses. In this study, 400 mm NaCl stress significantly induced the expression of Glutathione S-transferase U43 (SlGSTU43) in the roots of the wild-type tomato (Solanum lycopersicum L.) plants. Overexpressing SlGSTU43 enhanced the ability of scavenging reactive oxygen species in tomato leaves and roots under NaCl stress, while SlGSTU43 knock-out mutants showed the opposite performance. RNA sequencing analysis revealed that overexpressing SlGSTU43 affected the expression of genes related to lignin biosynthesis. We demonstrated that SlGSTU43 can regulate the lignin content in tomato through its interaction with SlCOMT2, a key enzyme involved in lignin biosynthesis, and promote the growth of tomato plants under NaCl stress. In addition, SlMYB71 and SlWRKY8 interact each other, and can directly bind to the promoter of SlGSTU43 to transcriptionally activate its expression separately or in combination. When SlMYB71 and SlWRKY8 were silenced in tomato plants individually or collectively, the plants were sensitive to NaCl stress, and their GST activities and lignin contents decreased. Our research indicates that SlGSTU43 can enhance salt stress tolerance in tomato by regulating lignin biosynthesis, which is regulated by interacting with SlCOMT2, as well as SlMYB71 and SlWRKY8. This finding broadens our understanding of GST functions., Competing Interests: Conflict of interest statement. The authors declare no conflict of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society of Plant Biologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objective: The purpose of this work was to develop an anti-CAT-SYI immunoglobulin Y (IgY) antibody that targeted both GtfB (glucosyltransferase B) and GbpB (glucan-binding protein B) and test its anticaries properties in rats., Methods: A new CAT-SYI fusion gene was created utilising functional DNA fragments from the GtfB and GbpB genes. The recombinant antigens, comprising the fused CAT-SYI antigen, GtfB, and GbpB, were expressed and purified using a prokaryotic expression and purification system. The purified recombinant antigens were utilised to immunise laying hens against particular IgY production. The biological activities of these particular IgY antibodies were then assessed both in vitro and in vivo, including their capacity to suppress biofilm formation and tooth caries., Results: Results indicated that these produced IgY antibodies demonstrated a high antibody titer (>0.1 μg/mL) and could precisely recognise and bind to their respective antigens. Furthermore, it was discovered that these specific IgY antibodies successfully bind to Streptococcus mutans and significantly reduce biofilm development. After 8 weeks of ingesting antigen-specific IgY meals, comprising anti-GtfB IgY and anti-GbpB IgY, the severity of dental caries was dramatically reduced in S mutans-infected Sprague-Dawley rats (P < .01). Anti-CAT-SYI IgY therapy significantly reduced tooth cavities by 89.0% in vivo (P < .05) compared to other treatment groups., Conclusions: The anti-CAT-SYI IgY, a multitarget antibody that targets both GtfB and GbpB, displayed excellent inhibitory effects against S mutans, making it a promising targeted method with improved anticaries efficacy and significant application opportunities., Competing Interests: Conflict of interest None disclosed., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Polycomb repressive complex 2 (PRC2) catalyzes the writing of the tri-methylated histone H3 at Lys27 (H3K27me3) epigenetic marker and suppresses the expression of genes, including tumor suppressors. The function of the complex can be partially antagonized by the SWI/SNF chromatin-remodeling complex. Previous studies have suggested that PRC2 is important for the proliferation of tumors with SWI/SNF loss-of-function mutations. In the present study, we have developed an EED-directed allosteric inhibitor of PRC2 termed BR0063, which exhibits anti-proliferative properties in a subset of solid tumor cell lines harboring mutations of the SWI/SNF subunits, SMARCA4 or ARID1A. Tumor cells sensitive to BR0063 exhibited several distinct phenotypes, including cell senescence, which was mediated by the up-regulation of CDKN2A/p16. Further experiments revealed that the expression of p16 was suppressed in the BR0063-resistant cells via DNA hypermethylation in the CpG island (CGI) promoter region, rather than via PRC2 occupancy. The expression of TET1, which is required for DNA demethylation, was found to be inversely correlated with p16 CGI methylation, and this may serve as a biomarker for the prediction of resistance to PRC2 inhibitors in SWI/SNF LOF tumors., (© 2024. The Author(s).)

Saline-alkali stress is a widely distributed abiotic stress that severely limits plant growth. γ-Aminobutyric acid (GABA) accumulates rapidly in plants under saline-alkali stress, but the underlying molecular mechanisms and associated regulatory networks remain unclear. Here, we report a MYB-like protein, I-box binding factor (SlMYBI), which positively regulates saline-alkali tolerance through induced GABA accumulation by directly modulating the glutamate decarboxylase (GAD) gene SlGAD1 in tomato (Solanum lycopersicum L.). Overexpression of SlGAD1 increased GABA levels and decreased reactive oxygen species accumulation under saline-alkali stress, while silencing of SlGAD1 further suggested that SlGAD1 plays an active role in GABA synthesis and saline-alkali tolerance of tomato. In addition, we found that SlMYBI activates SlGAD1 transcription. Both overexpression of SlMYBI and editing of SlMYBI using CRISPR-Cas9 showed that SlMYBI regulates GABA synthesis by modulating SlGAD1 expression. Furthermore, the interaction of SlNF-YC1 with SlMYBI enhanced the transcriptional activity of SlMYBI on SlGAD1 to further improve saline-alkali tolerance in tomato. Interestingly, we found that ethylene signaling was involved in the GABA response to saline-alkali stress by RNA-seq analysis of SlGAD1-overexpressing lines. This study elucidates the involvement of SlMYBI in GABA synthesis regulation. Specifically, the SlMYBI-SlNF-YC1 module is involved in GABA accumulation in response to saline-alkali stress., Competing Interests: Conflict of interest statement: The authors declare no conflict of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society of Plant Biologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background Cardiac MRI at 5 T has recently become available and potentially improves tissue contrast enhancement at gadolinium chelate-enhanced T1-weighted imaging. Purpose To evaluate the feasibility of 5-T myocardial late gadolinium enhancement (LGE) MRI in assessing myocardial fibrosis by comparing image quality and LGE quantification with reference-standard 3-T myocardial LGE MRI. Materials and Methods Consecutive patients with confirmed myocardial fibrosis on previous 3-T MRI scans between January 2023 and July 2023 prospectively underwent follow-up imaging from August 2023 to November 2023. Each participant underwent follow-up 5-T imaging using an identical dose of contrast agent. Radiologist scoring of image quality using a Likert scale (range, 1-5), signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), contrast ratio, and semiautomatic quantitative LGE assessment were obtained and reported as medians and IQRs. Paired Wilcoxon signed rank tests were used to compare characteristics derived at 3-T and 5-T imaging. Results A total of 18 participants (mean age, 49 years ± 17 [SD]; nine male participants) were included, with a mean interval of 6.2 months ± 2.3 between undergoing 3-T and 5-T MRI. Median image quality scores were 4.0 (IQR, 3.0-4.2) at 3 T and 4.0 (IQR, 3.0-4.4) at 5 T ( P = .45). SNR at 5 T was higher than at 3 T (183.7 [IQR, 147.2-255.9] vs 125.8 [IQR, 108.2-171.6], respectively; P = .002). Median CNR at 5 T was higher than at 3 T in normal myocardium (50.8 [IQR, 35.4-67.9] vs 16.5 [IQR, 11.3-24.6], respectively) and pericardial fat (21.4 [IQR, 7.1-29.3] vs -5.0 [IQR, -16.4 to -2.3], respectively) (both P < .001). There was no evidence of a difference in the percentage of LGE quantified between 5 T and 3 T (median, 11.8% [IQR, 7.7%-20.5%] vs 12.6% [IQR, 6.6%-20.4%], respectively; P = .81). Conclusion Myocardial LGE MRI at 5 T was found to be feasible, with no evidence of differences in subjective image quality and myocardial fibrosis quantification compared with 3-T myocardial LGE MRI. Furthermore, with use of identical contrast agent doses, SNRs and CNRs were improved at 5 T. Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Czum in this issue.

Purpose: Magnetic resonance imaging (MRI) refers to one of the critical image modalities for diagnosis, whereas its long acquisition time limits its application. In this study, the aim was to investigate whether deep learning-based techniques are capable of using the common information in different MRI sequences to reduce the scan time of the most time-consuming sequences while maintaining the image quality., Method: Fully sampled T1-FLAIR, T2-FLAIR, and T2WI brain MRI raw data originated from 217 patients and 105 healthy subjects. The T1-FLAIR and T2-FLAIR sequences were subsampled using Cartesian masks based on four different acceleration factors. The fully sampled T1/T2-FLAIR images were predicted from undersampled T1/T2-FLAIR images and T2WI images through deep learning-based reconstruction. They were qualitatively assessed by two senior radiologists in accordance with the diagnosis decision and a four-point scale image quality score. Furthermore, the images were quantitatively assessed based on regional signal-to-noise ratios (SNRs) and contrast-to-noise ratios (CNRs). The chi-square test was performed, where p < 0.05 indicated a difference with statistical significance., Results: The diagnosis decisions from two senior radiologists remained unchanged in accordance with the accelerated and fully sampled images. There were no significant differences in the regional SNRs and CNRs of most assessed regions (p > 0.05) between the accelerated and fully sampled images. Moreover, no significant difference was identified in the image quality assessed by two senior radiologists (p > 0.05)., Conclusion: Deep learning-based image reconstruction is capable of significantly expediting the brain MR imaging process and producing acceptable image quality without affecting diagnosis decisions., (© 2024 The Author(s). Brain and Behavior published by Wiley Periodicals LLC.)

Objective: T2-weighted 2D fast spin echo sequence serves as the standard sequence in&#xD;clinical pelvic MR imaging protocols. However, motion artifacts and blurring caused&#xD;by peristalsis present significant challenges. Patient preparation such as administering&#xD;antiperistaltic agents is often required before examination to reduce artifacts, which&#xD;discomfort the patients. This work introduce a novel dynamic approach for T2&#xD;weighted pelvic imaging to address peristalsis-induced motion issue without any patient&#xD;preparation.&#xD;Approach: A rapid dynamic data acquisition strategy with complementary sampling&#xD;trajectory is designed to enable highly undersampled motion-resistant data sampling,&#xD;and an unrolling method based on deep equilibrium model is leveraged to reconstruct&#xD;images from the dynamic sampled k-space data. Moreover, the fix-point convergence of&#xD;the equilibrium model ensures the stability of the reconstruction. The high acceleration&#xD;factor in each temporal phase, which is much higher than that in traditional static&#xD;imaging, has the potential to effectively freeze pelvic motion, thereby transforming&#xD;the imaging problem from conventional motion prevention or removal to motion&#xD;reconstruction.&#xD;Main results: Experiments on both retrospective and prospective data have&#xD;demonstrated the superior performance of the proposed dynamic approach in reducing&#xD;motion artifacts and accurately depicting structural details compared to standard static&#xD;imaging.&#xD;Significance: The proposed dynamic approach effectively captures motion states&#xD;through dynamic data acquisition and deep learning-based reconstruction, addressing&#xD;motion-related challenges in pelvic imaging., (© 2024 Institute of Physics and Engineering in Medicine. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Thermosensitive transient receptor potential (thermoTRP) ion channels can transduce external thermal stimuli to neural electrical signals, allowing organisms to detect and respond to changes in environmental temperature. Reproducing such ionic machinery holds promise for advancing the design of highly efficient low-grade thermal energy harvesters and ultrasensitive thermal sensors. However, there still exist challenges for artificial nanofluidic architectures to achieve comparable thermoelectric performance. Here, we report nanofluidic thermoelectric transducers with ultrahigh and tunable sensitivities controlled by electrostatic gating in graphene nanochannels. The equivalent Seebeck coefficient can be significantly boosted and reaches 1 order of magnitude higher than the current state of the art, even beyond thermoTRP ion channels. The improvement is attributed to substantial slippage on the highly charged graphene surface, leading to enhanced electrokinetic ion transport inside the graphene channel, which is confirmed by a scaling theory for thermoelectric coupling as well as molecular dynamic simulations. The dependence of the nanofluidic thermoelectric on the concentration, channel size, and cation types is also investigated to further clarify the underlying mechanism.

Background Coronary MR angiography (CMRA) at 3 T offers higher signal to noise ratio and contrast to noise ratio compared with 1.5 T. CMRA at 5 T may provide better diagnostic performance. Purpose To assess the feasibility and clinical application of 5-T noncontrast whole-heart CMRA and compare 5-T acquisition with 3-T acquisition. Materials and Methods From September 2023 to April 2024, patients scheduled for coronary CT angiography (CCTA) and volunteers were prospectively recruited. CCTA served as the reference standard in patients. CMRA was performed using a 3-T spectral attenuated inversion-recovery (3T SPAIR ) sequence and 3-T Dixon (3T Dixon ) sequence with routine spatial resolution (3T SPAIR-routine and 3T Dixon-routine , respectively), and 5-T Dixon (5T Dixon ) with routine and high spatial resolution (5T Dixon-routine and 5T Dixon-high , respectively). The study evaluated image quality, coronary artery calcium (CAC), the severity of coronary artery disease (CAD) graded according to Coronary Artery Disease Reporting and Data System, and the presence of ≥50% coronary stenosis. The nonparametric paired Wilcoxon signed rank test, McNemar test, generalized estimating equation model, and kappa test were used. Results Eight volunteers and 79 patients were included (mean age, 52 years ± 11 [SD]; 48 male). Image quality was higher for 5T Dixon-routine compared with 3T SPAIR-routine and 3T Dixon-routine ( P < .001 for both) and similar for 5T Dixon-high ( P = .60). The per-segment sensitivity for CAC was higher at 5T Dixon-high than 5T Dixon-routine (78.3% vs 53.3%; P < .001), with no difference in specificity (98.6% vs 98.6%; P > .99). In grading the severity of CAD, 5T Dixon-routine showed better consistency with CCTA than 3T SPAIR-routine (κ = 0.46 vs 0.13) and 3T Dixon-routine (κ = 0.55 vs 0.42). For detecting ≥50% stenosis, the per-patient sensitivity, specificity, and accuracy were as follows: 5T Dixon-routine versus 3T SPAIR-routine , 88.9% versus 55.6%, 86.5% versus 62.2%, and 87.0% versus 60.9% ( P = .55, .01, and .18, respectively); 5T Dixon-routine versus 3T Dixon-routine , 90.0% versus 80.0%, 86.8% versus 71.1%, and 87.5% versus 72.9%, respectively ( P > .05 for all). Conclusion Noncontrast CMRA at 5 T shows potential to evaluate CAC and coronary stenosis simultaneously and demonstrates superior diagnostic performance compared with at 3 T. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Rahsepar and Kim in this issue.

The aberrant activation of FGFR acts as a potent driver of multiple types of human cancers. Despite the development of several conventional small-molecular FGFR inhibitors, their clinical efficacy is largely compromised because of low selectivity and side effects. In this study, we report the selective FGFR1/2-targeting proteolysis-targeting chimera BR-cpd7 that displays significant isoform specificity to FGFR1/2 with half maximal degradation concentration values around 10 nmol/L while sparing FGFR3. The following mechanistic investigation reveals the reduced FGFR signaling, through which BR-cpd7 induces cell-cycle arrest and consequently blocks the proliferation of multiple FGFR1/2-dependent tumor cells. Importantly, BR-cpd7 has almost no antiproliferative activity against cancer cells without FGFR aberrations, furtherly supporting its selectivity. In vivo, BR-cpd7 exhibits robust antitumor effects in FGFR1-dependent lung cancer at well-tolerated dose schedules, accompanied by complete FGFR1 depletion. Overall, we identify BR-cpd7 as a promising candidate for developing a selective FGFR1/2-targeted agent, thereby offering a new therapeutic strategy for human cancers in which FGFR1/2 plays a critical role., (©2024 American Association for Cancer Research.)

Modern tomatoes produce colorful mature fruits, but many wild tomato ancestors form green or gray green ripe fruits. Here, tomato cultivar 'Lvbaoshi' (LBS) that produces green ripe fruits was found to contain three recessive loci responsible for fruit development. The colorless peel of LBS fruits was caused by a 603 bp deletion in the promoter of SlMYB12. The candidate genes of the remaining two loci were identified as STAY-GREEN 1 (SlSGR1) and PHYTOENE SYNTHASE 1 (SlPSY1). SGR1 and PSY1 co-suppression by RNAi converted the pink fruits into green ripe fruits in transgenic plants. An amino acid change in PSY1 and a deletion in the promoter of SGR1 were also identified in several wild tomatoes bearing green or gray ripe fruits. Overexpression of PSY1 from green ripe fruit wild tomatoes in LBS plants could only partially rescue the green ripe fruit phenotype of LBS, and transgenic lines expressing ProSGR1::SGR1 from Solanum pennellii also failed to convert purple-flesh into red-flesh fruits. This work uncovers a novel regulatory mechanism by which SlMYB12, SlPSY1, and SlSGR1 control fruit color in cultivated and some wild tomato species., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Saline-alkali stress is an important abiotic stress factor affecting tomato (Solanum lycopersicum L.) plant growth. Although the involvement of the tomato SlWRKY gene family in responses to saline-alkali stress has been well established, the mechanism underlying resistance to saline-alkali stress remains unclear. In this study, we investigated the role of SlWRKY81 in conferring saline-alkali stress resistance by using overexpression and knockout tomato seedlings obtained via genetic modification. We demonstrated that SlWRKY81 improves the ability of tomato to withstand saline-alkali stress by enhancing antioxidant capacity, root activity, and proline content while reducing malondialdehyde levels. Saline-alkali stress induces an increase in jasmonic acid (JA) content in tomato seedlings, and the SlWRKY81 promoter responds to JA signaling, leading to an increase in SlWRKY81 expression. Furthermore, the interaction between SlJAZ1 and SlWRKY81 represses the expression of SlWRKY81. SlWRKY81 binds to W-box motifs in the promoter regions of SlSPDS2 and SlNHX4, thereby positively regulating their expression. This regulation results in increased spermidine (Spd) content and enhanced potassium (K + ) absorption and sodium (Na + ) efflux, which contribute to the resistance of tomato to saline-alkali stress. However, JA and SlJAZ1 exhibit antagonistic effects. Elevated JA content reduces the inhibitory effect of SlJAZ1 on SlWRKY81, leading to the release of additional SlWRKY81 protein and further augmenting the resistance of tomato to saline-alkali stress. In summary, the modulation of Spd synthesis and Na + /K + homeostasis mediated by the interaction between SlWRKY81 and SlJAZ1 represents a novel pathway underlying tomato response to saline-alkali stress., (© 2024 Society for Experimental Biology and John Wiley & Sons Ltd.)

The aberrant activation of fibroblast growth factor receptor (FGFR) acts as a potent driver of multiple types of human cancers. Despite the development of several conventional small-molecular FGFR inhibitors, their clinical efficacy is largely compromised due to low selectivity and side effects. Here, we report the selective FGFR1/2-targeting proteolysis targeting chimeric (PROTAC), BR-cpd7 that displays significant isoform specificity to FGFR1/2 with DC50 values around 10 nM, while sparing FGFR3. The following mechanistic investigation reveals the reduced FGFR signaling, through which BR-cpd7 induces cell cycle arrest and consequently blocks the proliferation of multiple FGFR1/2-dependent tumor cells. Importantly, BR-cpd7 has almost no anti-proliferative activity against cancer cells without FGFR aberrations, furtherly supporting its selectivity. In vivo, BR-cpd7 exhibits robust antitumor effects in FGFR1-dependent lung cancer at well-tolerated dose schedules, accompanied by complete FGFR1 depletion. Overall, we identify BR-cpd7 as a promising candidate for developing a selective FGFR1/2-targeted agent, thereby offering a new therapeutic strategy for human cancers in which FGFR1/2 plays a critical role.

Flowering time, an important factor in plant adaptability and genetic improvement, is regulated by various genes in tomato (Solanum lycopersicum). In this study, we characterized a tomato mutant, EARLY FLOWERING (EF), that developed flowers much earlier than its parental control. EF is a dominant gain-of-function allele with a T-DNA inserted 139 bp downstream of the stop codon of FANTASTIC FOUR 1/2c (FAF1/2c). The transcript of SlFAF1/2c was at elevated levels in the EF mutant. Overexpressing SlFAF1/2c in tomato plants phenocopied the early flowering trait of the EF mutant. Knocking out SlFAF1/2c in the EF mutant reverted the early flowering phenotype of the mutant to the normal flowering time of the wild-type tomato plants. SlFAF1/2c promoted the floral transition by shortening the vegetative phase rather than by reducing the number of leaves produced before the emergence of the first inflorescence. The COP9 signalosome subunit 5B (CSN5B) was shown to interact with FAF1/2c, and knocking out CSN5B led to an early flowering phenotype in tomato. Interestingly, FAF1/2c was found to reduce the accumulation of the CSN5B protein by reducing its protein stability. These findings imply that FAF1/2c regulates flowering time in tomato by reducing the accumulation and stability of CSN5B, which influences the expression of SINGLE FLOWER TRUSS (SFT), JOINTLESS (J) and UNIFLORA (UF). Thus, a new allele of SlFAF1/2c was discovered and found to regulate flowering time in tomato., (© 2023 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.)

Saline-alkali is an important abiotic stressor influencing tomato production. Exogenous methyl jasmonate (MeJA) is well known to increase tomato resistance to a variety of stresses, although its exact mechanism is yet unknown. In this study we confirmed that 22.5 μmol/l MeJA could significantly improve the saline-alkali stress resistance of tomato. Saline-alkali (300 mM) stress increased the endogenous MeJA and jasmonic acid (JA) contents of tomato by 18.8 and 13.4%, respectively. Exogenous application of 22.5 μmol/l MeJA increased the endogenous MeJA and JA contents in tomato by 15.2 and 15.9%, respectively. Furthermore, we found an important transcription factor, SlWRKY80 , which responded to MeJA, and constructed its overexpressing and knockout lines through genetic transformation. It was found that SlWRKY80 actively regulated tomato resistance to saline-alkali stress, and the spraying of exogenous MeJA (22.5 μmol/l) reduced the sensitivity of SlWRKY80 knockout lines to saline-alkali stress. The SlWRKY80 protein directly combines with the promoter of SlSPDS2 and SlNHX4 to positively regulate the transcription of SlSPDS2 and SlNHX4 , thereby promoting the synthesis of spermidine and Na + /K + homeostasis, actively regulating saline-alkali stress. The augmentation of JA content led to a notable reduction of 70.6% in the expression of SlJAZ1 , and the release of the SlWRKY80 protein interacting with SlJAZ1. In conclusion, we revealed the mechanism of exogenous MeJA in tomato stress resistance through multiple metabolic pathways, elucidated that exogenous MeJA further promotes spermidine synthesis and Na + /K + homeostasis by activating the expression of SlWRKY80 , which provides a new theoretical basis for the study of the JA stress resistance mechanism and the production of tomato., Competing Interests: The authors declare no competing commercial or financial interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nanjing Agricultural University.)

DC1 (Divergent C1) domain proteins are a new class of proteins that have been discovered in recent years, which play an important role in plant growth, development, and stress response. In order to better study the distribution and function of DC1 domain proteins in tomatoes, a genome-wide identification was conducted. It was found that there are twenty-one DC1 domain protein genes distributed on nine chromosomes of tomatoes, named SlCHP1-21 . Phylogenetic analysis shows that twenty-one SlCHP genes are divided into six subfamilies. Most of the SlCHP genes in tomatoes have no or very short introns. All SlCHP proteins, with the exception of SlCHP8 and SlCHP17, contain variable amounts of C1 domain. Analysis of the SlCHP gene promoter sequence revealed multiple cis-elements responsive to plant stress. qRT-CR analysis showed that most members of SlCHP gene expressed in the roots. The SlCHP11 , 13 , 16 , 17, and SlCHP20 genes showed specific responses to high temperature, low temperature, salt, and drought stress. In addition, the subcellular localization and interaction proteins of SlCHP were analyzed and predicted. Together, these results provides a theoretical basis for further exploration of the function and mechanism of the SlCHP gene in tomatoes.

While deep learning has found widespread utility in gearbox fault diagnosis, its direct application to wind turbine gearboxes encounters significant hurdles. Disparities in data distribution across a spectrum of operating conditions for wind turbines result in a marked decrease in diagnostic accuracy. In response, this study introduces a tailored dynamic conditional adversarial domain adaptation model for fault diagnosis in wind turbine gearboxes amidst cross-condition scenarios. The model adeptly adjusts the importance of aligning marginal and conditional distributions using distance metric factors. Information entropy parameters are also incorporated to assess individual sample transferability, prioritizing highly transferable samples during domain alignment. The amalgamation of these dynamic factors empowers the approach to maintain stability across varied data distributions. Comprehensive experiments on both gear and bearing data validate the method's efficacy in cross-condition fault diagnosis. Comparative outcomes demonstrate that, when contrasted with four advanced transfer learning techniques, the dynamic conditional adversarial domain adaptation model attains superior accuracy and stability in multi-transfer tasks, making it notably suitable for diagnosing wind turbine gearbox faults.

Purpose: To propose an acceleration method for 3D variable flip-angle (VFA) T 1 mapping based on a technique called shift undersampling improves parametric mapping efficiency and resolution (SUPER)., Methods: The proposed method incorporates strategies of SUPER, controlled aliasing in volumetric parallel imaging (CAIPIRINHA), and total variation-based regularization to accelerate 3D VFA T 1 mapping. The k-space sampling grid of CAIPIRINHA is internally undersampled with SUPER along the contrast dimension. A proximal algorithm was developed to preserve the computational efficiency of SUPER in the presence of regularization. The regularized SUPER-CAIPIRINHA (rSUPER-CAIPIRINHA) was compared with low rank plus sparsity (L + S), reconstruction of principal component coefficient maps (REPCOM), and other SUPER-based methods via simulations and in vivo brain T 1 mapping. The results were assessed quantitatively with NRMSE and structural similarity index measure (SSIM), and qualitatively by two experienced reviewers., Results: rSUPER-CAIPIRINHA achieved a lower NRMSE and higher SSIM than L + S (0.11 ± 0.01 vs. 0.19 ± 0.03, p < 0.001; 0.66 ± 0.05 vs. 0.37 ± 0.03, p < 0.001) and REPCOM (0.16 ± 0.02, p < 0.001; 0.46 ± 0.04, p < 0.001). The reconstruction time of rSUPER-CAIPIRINHA was 6% of L + S and 2% of REPCOM. For the qualitative comparison, rSUPER-CAIPIRINHA showed improvement of overall image quality and reductions of artifacts and blurring, although with a lower apparent SNR. Compared with 2D SUPER-SENSE, rSUPER-CAIPIRINHA significantly reduced NRMSE (0.11 ± 0.01 vs. 0.23 ± 0.04, p < 0.001) and generated less noisy reconstructions., Conclusion: By incorporating SUPER, CAIPIRINHA, and regularization, rSUPER-CAIPIRINHA mitigated noise amplification, reduced artifacts and blurring, and achieved faster reconstructions compared with L + S and REPCOM. These advantages render 3D rSUPER-CAIPIRINHA VFA T 1 mapping potentially useful for clinical applications., (© 2023 International Society for Magnetic Resonance in Medicine.)

Fast and low-dose reconstructions of medical images are highly desired in clinical routines. We propose a hybrid deep-learning and iterative reconstruction (hybrid DL-IR) framework and apply it for fast magnetic resonance imaging (MRI), fast positron emission tomography (PET), and low-dose computed tomography (CT) image generation tasks. First, in a retrospective MRI study (6,066 cases), we demonstrate its capability of handling 3- to 10-fold under-sampled MR data, enabling organ-level coverage with only 10- to 100-s scan time; second, a low-dose CT study (142 cases) shows that our framework can successfully alleviate the noise and streak artifacts in scans performed with only 10% radiation dose (0.61 mGy); and last, a fast whole-body PET study (131 cases) allows us to faithfully reconstruct tumor-induced lesions, including small ones (<4 mm), from 2- to 4-fold-accelerated PET acquisition (30-60 s/bp). This study offers a promising avenue for accurate and high-quality image reconstruction with broad clinical value., Competing Interests: Declaration of interests S.L., J.W., X.W., X.H., Y. Zhang, Y.W., Q.Z., Y.X., Y. Zhan, X.S.Z., F.S., and D.S. are employees of Shanghai United Imaging Intelligence Co., Ltd.; G.L., G.Q., Y.L., W.C., and Y.D. are employees of Shanghai United Imaging Healthcare Co., Ltd. The companies have no role in designing and performing the surveillance and analyzing and interpreting the data., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Multiple Gretchen Hagen 3 (GH3) genes have been implicated in a range of processes in plant growth and development through their roles in maintaining hormonal homeostasis. However, there has only been limited study on the functions of GH3 genes in tomato (Solanum lycopersicum). In this work, we investigated the important function of SlGH3.15, a member of the GH3 gene family in tomato. Overexpression of SlGH3.15 led to severe dwarfism in both the above- and below-ground sections of the plant, accompanied by a substantial decrease in free IAA content and reduction in the expression of SlGH3.9, a paralog of SlGH3.15. Exogenous supply of IAA negatively affected the elongation of the primary root and partially restored the gravitropism defects in SlGH3.15-overexpression lines. While no phenotypic change was observed in the SlGH3.15 RNAi lines, double knockout lines of SlGH3.15 and SlGH3.9 were less sensitive to treatments with the auxin polar transport inhibitor. Overall, these findings revealed important roles of SlGH3.15 in IAA homeostasis and as a negative regulator of free IAA accumulation and lateral root formation in tomato., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Endogenous spermidine can improve the resistance of plants to saline-alkali stress. SlSPDS1 and SlSPDS2 are the main spermidine synthase (SPDS) genes in tomatoes. In comparison with SlSPDS1, SlSPDS2 plays an important role in wild-type tomato seedling under saline-alkali stress. However, limited research has focused on the role of SlSPDS2 in saline-alkali stress. Wild-type (WT) and SPDS gene (SlSPDS2) transgenic over-expression tomato seedlings were used to explore the function of endogenous spermidine on the saline-alkali resistance of tomato seedlings. The results show that SlSPDS2 overexpression under normal conditions and saline-alkali stress increased the content of endogenous free polyamines and the expression levels of polyamine synthesis-related genes in tomato seedlings. Under saline-alkali stress, SlSPDS2 overexpression significantly reduced Na + /K + ratio, relative electrical conductivity, O 2 ·- , H 2 O 2 , and malondialdehyde content, increased Seedling index, relative water content, antioxidant enzyme activities (peroxidase, superoxide dismutase, and catalase), and the contents of proline and soluble sugar in tomato leaf, and mitigated the adverse effect of saline-alkali stress on tomato seedlings. In summary, the overexpression of SlSPDS2 tomato seedlings regulated the ionic homeostasis, antioxidant enzyme system, and osmotic regulatory substances of tomato seedlings living in saline-alkali environment by increasing endogenous free polyamine content, thereby improving the resistance of tomato seedlings against saline-alkali stress., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Osteoporosis and sarcopenia (termed "Osteosarcopenia"), the twin-aging diseases, are major contributors to reduced bone mass and muscle weakness in the elderly population. Connexin 43 (Cx43) in osteocytes has been previously reported to play vital roles in bone homeostasis and muscle function in mature mice. The Cx43-formed gap junctions (GJs) and hemichannels (HCs) in osteocytes are important portals for the exchange of small molecules in cell-to-cell and cell-to-extracellular matrix, respectively. However, the roles of Cx43-based GJs and HCs in both bone and muscle aging are still unclear. Here, we used two transgenic mouse models with overexpression of the dominant negative Cx43 mutants primarily in osteocytes driven by the 10-kb Dmp1 promoter, R76W mice (inhibited gap junctions but enhanced hemichannels) and Δ130-136 mice (both gap junction and hemichannels are inhibited), to determine the actions of Cx43-based hemichannels (HCs) and gap junctions (GJs) in the regulation of bone and skeletal muscle from aged mice (18 months) as compared with those from adult mice (10 months). We demonstrated that enhancement of Cx43 HCs reduces bone mass due to increased osteoclast surfaces while the impairment of Cx43 HCs increases osteocyte apoptosis in aged mice caused by reduced PGE 2 levels. Furthermore, altered mitochondrial homeostasis with reduced expression of Sirt-1, OPA-1, and Drp-1 resulted in excessive ROS level in muscle soleus (SL) of aged transgenic mice. In vitro, the impairment of Cx43 HCs in osteocytes from aged mice also promoted muscle collagen synthesis through activation of TGFβ/smad2/3 signaling because of reduced PGE 2 levels in the PO CM. These findings indicate that the enhancement of Cx43 HCs while GJs are inhibited reduces bone mass, and the impairment of Cx43 HCs inhibits PGE 2 level in osteocytes and this reduction promotes muscle collagen synthesis in skeletal muscle through activation of TGFβ/smad2/3 signaling, which together with increased ROS level contributes to reduced muscle force in aged mice.

Path planning for wheeled mobile robots on partially known uneven terrain is an open challenge since robot motions can be strongly influenced by terrain with incomplete environmental information such as locally detected obstacles and impassable terrain areas. This paper proposes a hierarchical path planning approach for a wheeled robot to move in a partially known uneven terrain. We first model the partially known uneven terrain environment respecting the terrain features, including the slope, step, and unevenness. Second, facilitated by the terrain model, we use A⋆ algorithm to plan a global path for the robot based on the partially known map. Finally, the Q -learning method is employed for local path planning to avoid locally detected obstacles in close range as well as impassable terrain areas when the robot tracks the global path. The simulation and experimental results show that the designed path planning approach provides satisfying paths that avoid locally detected obstacles and impassable areas in a partially known uneven terrain compared with the classical A⋆ algorithm and the artificial potential field method.

Objective: Currently, the treatment of spontaneous intracerebral hemorrhage (sICH) is limiting, especially in patients with midline shift and supratentorial hemorrhage. Here, we investigated the clinical value of minimally invasive surgery (MIS) in patients with midline shift and supratentorial sICH by observing the consciousness state, midline shift, and short-term mortality., Methods: A total of 124 supratentorial sICH patients with midline shift, hematoma volume >30 mL and <150 mL were included in this study. Based on treatment methods, the enrolled patients were divided into minimally invasive surgical (MIS) (group 1, n = 61) and conservative (group 2, n = 63) treatment groups. Measurements of midline shift and state of consciousness using the Glasgow Coma Scale (GCS) score were performed on day 2 following treatment. Additionally, mortality, adverse events, and neurologic recovery (modified Rankin Scale score) in each group were observed after 1 month., Results: On postoperative day 2, the recovery rates of midline shift and consciousness state in group 1 patients were 59.02% and 50.82%, respectively, significantly higher than group 2, 26.98% and 25.40% (P < 0.01). By comparing death, adverse events, and neurologic function recovery of the 2 groups within 1 month postoperative, we observed a significantly lower fatality rate in group 1 (16.39%; 10 cases) than group 2 (33.33%; 21 cases) (P < 0.05). No significant difference of the adverse event rates was observed between groups 1 and 2 (19.67% [12 cases] vs. 19.05% [12 cases]). In addition, neurologic function recovery also had no significant difference between the 2 groups (P > 0.05)., Conclusions: MIS could reduce early-stage midline shift, improve consciousness state and reduce short-term mortality in patients with supratentorial sICH., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Angiopoietin-like 2 (Angptl2) is reported to be correlated with cardiovascular diseases, but its role in hypertension remains unclear. This study aimed to investigate the role and potential mechanism of Angptl2 in hypertension. Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs) were used to detect the expression of Angptl2. Angiotensin II (Ang II) stimulates vascular smooth muscle cells (VSMCs) to mimic hypertension in vitro. Cell proliferation, migration, and invasion abilities were determined using CCK-8, cell colony formation, wound healing, and transwell assays, respectively. The cell cycle distribution was detected by flow cytometry. The expression of Ki67 was determined by immunofluorescence, and protein expression was measured using western blotting. Angptl2 was found to be elevated in hypertensive rats in vivo and in VSMCs upon Ang II stimulation in vitro. Angptl2 knockdown suppressed cell proliferation, colony formation, cell migration, and invasion as well as the downregulation of Ki67. Additionally, Angptl2 knockdown hindered cell cycle progression and downregulated protein expression of CDK2/4 and cyclin D1, but upregulated p21 expression. Furthermore, Angptl2 knockdown inhibited activation of the NLRP3 inflammasome. Our findings suggest that Angptl2 knockdown suppresses VSMC proliferation, migration, and invasion induced by Ang II. Angptl2 may be a new target for vascular remodeling in hypertension.

The cleanliness of hydraulic oil can reflect the service life of the oil and the wear state of hydraulic machinery. An impedance sensor is proposed to distinguish multi-contaminants in hydraulic oil. The impedance sensor has two detection modes: the inductance-resistance mode is used to detect metal debris, and the capacitance mode is used to distinguish water droplets and air bubbles. By adding a built-in silicon steel strip and an external silicon steel strip with high magnetic permeability, the distribution area, strength, and uniformity of the magnetic field are enhanced to improve the detection sensitivity under inductance and resistance parameters. In addition, the silicon steel strips are used as electrode plates to introduce capacitance parameter detection. The experimental results show that the resistance detection method based on coil successfully improves the detection ability for non-ferromagnetic metal debris. The impedance sensor for distinguishing multi-contaminants in hydraulic oil can provide technical support for fault diagnosis of offshore hydraulic machinery.

Although autocatalytic ethylene biosynthesis plays an important role in the ripening of climacteric fruits, our knowledge of the network that promotes it remains limited. We identified white fruit (wf), a tomato mutant that produces immature fruit that are white and that ripen slowly. We found that an inversion on chromosome 10 disrupts the LUTESCENT2 (L2) gene, and that white fruit is allelic to lutescent2. Using CRISPR/Cas9 technology we knocked out L2 in wild type tomato and found that the l2-cr mutants produced phenotypes that were very similar to white fruit (lutescent2). In the l2-cr fruit, chloroplast development was impaired and the accumulation of carotenoids and lycopene occurred more slowly than in wild type. During fruit ripening in l2-cr mutants, the peak of ethylene release was delayed, less ethylene was produced, and the expression of ACO genes was significantly suppressed. We also found that exogenous ethylene induces the expression of L2 and that ERF.B3, an ethylene response factor, binds to the promoter of the L2 gene and activates its transcription. Thus, the expression of L2 is regulated by exogenous ethylene. Taken together, our results indicate that ethylene may affect the expression of L2 gene and that L2 participates in autocatalytic ethylene biosynthesis during tomato fruit ripening., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

An inductive oil pollutant detection sensor based on a high-gradient magnetic field structure is designed in this paper, which is mainly used for online detection and fault analysis of pollutants in hydraulic and lubricating oil systems. The innovation of the sensor is based on the inductance detection method. Permalloy is embedded in the sensing region of the sensor, so that the detection area generates a high gradient magnetic field to enhance the detection accuracy of the sensor. Compared with traditional inductive sensors, the sensor has a significant improvement in detection accuracy, and the addition of permalloy greatly improves the stability of the sensor's detection unit structure. The article theoretically analyzes the working principle of the sensor, optimizes the design parameters and structure of the sensor through simulation, determines the best permalloy parameters, and establishes an experimental system for verification. Experimental results show that when a piece of permalloy is added to the sensing unit, the signal-to-noise ratio (SNR) of iron particles is increased by more than 20%, and the signal-to-noise ratio of copper particles is increased by more than 70%. When two pieces of permalloy are added, the signal-to-noise ratio for iron particles is increased by more than 70%, and the SNR for copper particles is increased several times. This method raises the lower limit of detection for ferromagnetic metal particles to 20 μm, and the lower limit for detection of non-ferromagnetic metal particles to 80 μm, which is the higher detection accuracy of the planar coil sensors. This paper provides a new and faster online method for pollutant detection in oil, which is of great significance for diagnosing and monitoring the health of oil in mechanical systems.

Osteocytes could release some small molecules (≤ 1 kDa) through gap junctions and hemichannels to extracellular environment, such as prostaglandin E2 (PGE2), nitric oxide (NO) and adenosine triphosphate (ATP), which play key roles in transferring signals between bone cells and other tissue cells. Connexin (Cx) 43 is the most abundant connexin in osteocytes. To further discover molecules released by osteocytes through Cx43 channels and better understand the regulatory function of Cx43 channels in osteocytes, we performed non-targeted global metabolomics analysis using liquid chromatography-tandem mass spectrometry (LC-MS/MS) on conditioned medium collected from osteocytes isolated from two transgenic mouse models with Cx43 dominant negative mutants driven by a 10 kb-DMP1 promoter: R76W (gap junctions are blocked, whereas hemichannels are promoted) and Δ130-136 (both gap junctions and hemichannels are blocked). The results revealed that several new categories of molecules, such as "fatty acyls" and "carboxylic acids and derivatives", could be released through osteocytic Cx43 channels. In addition, alteration of Cx43 channel function affected the release of metabolites related to inflammatory reaction and oxidative stress. Pathway analysis further showed that citric acid cycle was the most differential metabolic pathway regulated by Cx43 channels. In sum, these results isolated new potential metabolites released by osteocytes through Cx43 channels, and offered a novel perspective to understand the regulatory mechanisms of osteocytes on themselves and other cells as well., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chen, Li, Zhang, Ning, Yang, Jiang, Wang and Xu.)

DNA-binding proteins (DBPs) play pivotal roles in many biological functions such as alternative splicing, RNA editing, and methylation. Many traditional machine learning (ML) methods and deep learning (DL) methods have been proposed to predict DBPs. However, these methods either rely on manual feature extraction or fail to capture long-term dependencies in the DNA sequence. In this paper, we propose a method, called PDBP-Fusion, to identify DBPs based on the fusion of local features and long-term dependencies only from primary sequences. We utilize convolutional neural network (CNN) to learn local features and use bi-directional long-short term memory network (Bi-LSTM) to capture critical long-term dependencies in context. Besides, we perform feature extraction, model training, and model prediction simultaneously. The PDBP-Fusion approach can predict DBPs with 86.45% sensitivity, 79.13% specificity, 82.81% accuracy, and 0.661 MCC on the PDB14189 benchmark dataset. The MCC of our proposed methods has been increased by at least 9.1% compared to other advanced prediction models. Moreover, the PDBP-Fusion also gets superior performance and model robustness on the PDB2272 independent dataset. It demonstrates that the PDBP-Fusion can be used to predict DBPs from sequences accurately and effectively; the online server is at http://119.45.144.26:8080/PDBP-Fusion/., Competing Interests: The authors declare there are no competing interests., (©2021 Li et al.)

NF-Y transcription factors are reported to play diverse roles in a wide range of biological processes in plants. However, only a few active NF-Y complexes are known in plants and the precise functions of NF-Y complexes in flavonoid biosynthesis have not been determined. Using various molecular, genetic and biochemical approaches, we found that NF-YB8a, NF-YB8b and NF-YB8c - a NF-YB subgroup - can interact with a specific subgroup of NF-YC and then recruit either of two distinct NF-YAs to form NF-Y complexes that bind the CCAAT element in the CHS1 promoter. Furthermore, suppressing the expression of particular NF-YB genes increased the levels of H3K27me3 at the CHS1 locus and significantly suppressed the expression of CHS1 during tomato fruit ripening, which led to the development of pink-coloured fruit with colourless peels. Altogether, by demonstrating that NF-Y transcription factors play essential roles in flavonoid biosynthesis and by providing significant molecular insight into the regulatory mechanisms that drive the development of pink-coloured tomato fruit, we provide a major advance to our fundamental knowledge and information that has considerable practical value for horticulture., (© 2020 The Authors New Phytologist © 2020 New Phytologist Foundation.)

Bone-muscle crosstalk plays an important role in skeletal biomechanical function, the progression of numerous pathological conditions, and the modulation of local and distant cellular environments. Previous work has revealed that the deletion of connexin (Cx) 43 in osteoblasts, and consequently, osteocytes, indirectly compromises skeletal muscle formation and function. However, the respective roles of Cx43-formed gap junction channels (GJs) and hemichannels (HCs) in the bone-muscle crosstalk are poorly understood. To this end, we used two Cx43 osteocyte-specific transgenic mouse models expressing dominant negative mutants, Δ130-136 (GJs and HCs functions are inhibited), and R76W (only GJs function is blocked), to determine the effect of these two types of Cx43 channels on neighboring skeletal muscle. Blockage of osteocyte Cx43 GJs and HCs in Δ130-136 mice decreased fast-twitch muscle mass with reduced muscle protein synthesis and increased muscle protein degradation. Both R76W and Δ130-136 mice exhibited decreased muscle contractile force accompanied by a fast-to-slow fiber transition in typically fast-twitch muscles. In vitro results further showed that myotube formation of C2C12 myoblasts was inhibited after treatment with the primary osteocyte conditioned media (PO CM) from R76W and Δ130-136 mice. Additionally, prostaglandin E2 (PGE2) level was significantly reduced in both the circulation and PO CM of the transgenic mice. Interestingly, the injection of PGE2 to the transgenic mice rescued fast-twitch muscle mass and function; however, this had little effect on protein synthesis and degradation. These findings indicate a channel-specific response: inhibition of osteocytic Cx43 HCs decreases fast-twitch skeletal muscle mass alongside reduced protein synthesis and increased protein degradation. In contrast, blockage of Cx43 GJs results in decreased fast-twitch skeletal muscle contractile force and myogenesis, with PGE2 partially accounting for the measured differences.

Purpose: Glioma is one of the most common malignant tumors affecting human health. Long non-coding RNA (lncRNA) TMPO-AS1 participates in the pathogenesis of various cancers. However, the role of lncRNA TMPO-AS1 in glioma remains largely unknown. This study aims to uncover the role of TMPO-AS1 and explore its potential mechanism in glioma., Methods: Expression levels of TMPO-AS1 and miR-383-5p in glioma cell lines were measured by real-time quantitative PCR (RT-qPCR). CCK-8, colony formation, wound-healing, and Transwell assays were conducted to determine cell proliferation, migration and invasion abilities, respectively. Western blotting was applied to detect the expression of corresponding proteins. Immunofluorescence assay was performed to measure the expression of Ki67. The binding condition between TMPO-AS1 and miR-383-5p was verified by dual-luciferase reporter assay., Results: We found that TMPO-AS1 was up-regulated while miR-383-5p was down-regulated in glioma cell lines, and knockdown of TMPO-AS1 significantly suppressed glioma cell proliferation, migration and invasion abilities. miR-383-5p was demonstrated to be a direct target of TMPO-AS1. Besides, inhibition of miR-383-5p abolished the effects of TMPO-AS1 knockdown on glioma cells., Conclusion: In summary, our study revealed that inhibition of lncRNA TMPO-AS1 could suppress glioma progression through targeting miR-383-5p. TMPO-AS1 might be used as a therapeutic target for glioma treatment., Competing Interests: The authors report no conflicts of interest for this work., (© 2020 Liu et al.)

This work provides a simple method to prepare a hydrophilic/oleophobic coating using polyester filter cloth as the substrate, a mixture of three hydrophilic polymers (poly(aspartic acid), poly(acrylic acid), and poly(vinyl alcohol)); SiO 2 with an average particle size of 30 nm is used to improve the surface roughness of the filter cloth. Then, a long fluorocarbon chain of 1 H ,1 H ,2 H ,2 H -perfluorooctyltriethoxysilane is grafted onto the surface by a vacuum silanization coupling reaction to obtain hydrophilic/oleophobic properties. The water and hexadecane contact angles of the treated filter cloth are 3 and 99.8°, respectively. A separation efficiency of 98% was achieved in hexadecane/water separation. The durability test shows that the separation efficiency of toward hexadecane-water mixture remains more than 98% after 20 cycles. The obtained material also presents a strong underwater antipollution property when using hexane, rapeseed oil, mineral oil, and pump oil as model pollutants. For oils with higher viscosity, the separation efficiency remains above 97%. However, the separation efficiency is ∼80% when treating emulsions.

In order to improve the throughput and sensitivity of the inductive metal micro-abrasive particle detection sensor, this paper uses microfluidic detection technology to design a high-throughput abrasive particle detection sensor based on PDMS (Polydimethylsiloxane). Theoretical modeling analyzes the magnetization of metal abrasive particles in the coil's time-harmonic magnetic field, and uses COMSOL simulation to calculate the best performance parameters of the sensor. Through the experiment of the control variable method, the corresponding signal value is obtained and the signal-to-noise ratio (SNR) is calculated. The SNR value and error value are calculated, and the SNR is corrected. The detection limit of the sensor is determined to be 10 μm iron particles and 60 μm copper particles. The optimal design parameters of the 3-D solenoid coil and the frequency characteristics of the sensor are obtained. Finally, through high-throughput experiments and analysis, it was found that there was a reasonable error between the actual throughput and the theoretical throughput. The design ideas suggested in this article can not only improve the sample throughput, but also ensure the detection accuracy. This provides a new idea for the development of an inductive on-line detection method of abrasive particle technology.

Background: Colorectal cancer (CRC) is one of the causes of cancer-related death worldwide. The aim of our study was to disclose the expression pattern and underlying molecular mechanism of circular RNA TADA2A (circTADA2A) in CRC., Methods: The levels of circTADA2A, transcriptional adaptor 2A (TADA2A), microRNA-374a-3p (miR-374a-3p) and Kruppel like factor 14 (KLF14) were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Xenograft tumor assay was used to uncover the function of circTADA2A in vivo. The miRNA targets of circTADA2A were searched using circbank and starbase softwares, while DIANA TOOL was used to explore miR-374a-3p-mRNA interactions. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were performed to validate the target relationship of circTADA2A/miR-374a-3p/KLF14 axis. Cell cycle and apoptosis were analyzed by flow cytometry. The glycolysis of CRC cells was determined by Seahorse XF e 96 Extracellular Flux Analyzer, Glucose Uptake Colorimetric Assay kit, Lactate Assay Kit II and ATP Colorimetric Assay kit. KLF14 protein level was measured by Western blot assay., Results: CircTADA2A was abnormally down-regulated in CRC tissues and cell lines. CircTADA2A overexpression impeded CRC tumor growth in vivo. MiR-374a-3p was verified as a target of circTADA2A in CRC cells, and circTADA2A inhibited the malignant potential of CRC cells through targeting miR-374a-3p. MiR-374a-3p interacted with KLF14 messenger RNA (mRNA), and miR-374a-3p deteriorated CRC through down-regulating KLF14. CircTADA2A enhanced the abundance of KLF14 through targeting miR-374a-3p in CRC cells., Conclusion: CircTADA2A functioned as a tumor suppressor in CRC to inhibit the glycolysis and cell cycle and potentiate the apoptosis of CRC cells via miR-374a-3p/KLF14 axis.

Objective: In recent years, a number of case-control studies have focused on the association between the DJ-1 g.168&#95;185del polymorphism and the risk of Parkinson's disease (PD). However, the results have been conflicting. To estimate the relationship between the DJ-1 g.168&#95;185del polymorphism and PD susceptibility, a comprehensive meta-analysis was performed., Methods: Eligible studies concerning the DJ-1 g.168&#95;185del polymorphism and PD susceptibility were searched for in the PubMed, Web of Science, Embase, Wanfang, CNKI, and VIP databases. Odds ratios and 95% confidence intervals were calculated to estimate the strength of the associations. In total, 11 studies were included in this meta-analysis, including 13 case-control studies with 2890 cases and 3043 controls., Results: This meta-analysis revealed that DJ-1 g.168&#95;185del variants are associated with PD susceptibility in the non-Asian population, but not in the Asian population., Conclusions: Our meta-analysis suggests that DJ-1 gene variants are not associated with the risk of PD in the overall population.

Connexin (Cx) 43 forms gap junctions and hemichannels that mediate communication between osteocytes and adjacent cells or the extracellular environment in bone, respectively. To investigate the role of each channel type in response to mechanical unloading, two transgenic mouse models overexpressing dominant-negative Cx43 predominantly in osteocytes driven by a 10 kb dentin matrix protein 1 ( Dmp1 ) promoter were generated. The R76W mutation resulted in gap junction inhibition and enhancement of hemichannels, whereas the Δ130-136 mutation inhibited both gap junctions and hemichannels. Both mutations led to cortical bone loss with increased endocortical osteoclast activity during unloading. Increased periosteal osteoclasts with decreased apoptotic osteocytes were observed only in R76W mice. These findings indicated that inhibiting osteocytic Cx43 channels promotes bone loss induced by unloading, mainly in the cortical area; moreover, hemichannels protect osteocytes against apoptosis and promote periosteal bone remodeling, whereas gap junctions modulate endocortical osteoclast activity in response to unloading., (Copyright © 2020 Zhao, Liu, Li, Chen, Shang, Yang, Jiang and Xu.)

The cross-talk between cells is very critical for moving forward fracture healing in an orderly manner. Connexin (Cx) 43-formed gap junctions and hemichannels mediate the communication between adjacent cells and cells and extracellular environment. Loss of Cx43 in osteoblasts/osteocytes results in delayed fracture healing. For investigating the role of two channels in osteocytes in bone repair, two transgenic mouse models with Cx43 dominant negative mutants driven by a 10 kb-DMP1 promoter were generated: R76W (gap junctions are blocked, whereas hemichannels are promoted) and Δ130-136 (both gap junctions and hemichannels are blocked). R76W mice (promotion of hemichannels) showed a significant increase of new bone formation, whereas delayed osteoclastogenesis and healing was observed in Δ130-136 (impairment of gap junctions), but not in R76W mice (hemichannel promotion may recover the delay). These results suggest that gap junctions and hemichannels play some similar and cooperative roles in bone repair., (© 2019 Wiley Periodicals, Inc.)

The nature of muscle-bone crosstalk has been historically considered to be only mechanical, where the muscle is the load applier while bone provides the attachment sites. However, this dogma has been challenged with the emerging notion that bone and muscle act as secretory endocrine organs affect the function of each other. Biochemical crosstalk occurs through myokines such as myostatin, irisin, interleukin (IL)-6, IL-7, IL-15, insulin-like growth factor-1, fibroblast growth factor (FGF)-2, and β-aminoisobutyric acid and through bone-derived factors including FGF23, prostaglandin E 2 , transforming growth factor β, osteocalcin, and sclerostin. Aside from the biochemical and mechanical interaction, additional factors including aging, circadian rhythm, nervous system network, nutrition intake, and exosomes also have effects on bone-muscle crosstalk. Here, we summarize the current research progress in the area, which may be conductive to identify potential novel therapies for the osteoporosis and sarcopenia, especially when they develop in parallel., (© 2019 Wiley Periodicals, Inc.)

In the present study, we identified a novel circular RNA (circRNA), hsa&#95;circ&#95;0046701, in glioma cells. We measured the expression of hsa&#95;circ&#95;0046701 using qRT-PCR in glioma tissues and cell lines, and explored its functions using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, colony formation, and Transwell assays. Luciferase reporter assays were performed to validate the correlation between microRNA miR-142-3p and hsa&#95;circ&#95;0046701 or integrin subunit beta 8 (ITGB8). The results showed that hsa&#95;circ&#95;0046701 was significantly upregulated in glioma tissues and cell lines, and knockdown of hsa&#95;circ&#95;0046701 inhibited cell proliferation and invasion. Luciferase reporter assays indicated that hsa&#95;circ&#95;0046701 functions as a sponge for miR-142-3p and regulates the expression of ITGB8. Subsequently, functional assays revealed that silencing of hsa&#95;circ&#95;0046701 could upregulate miR-142-3p, resulting in downregulation of ITGB8. The results demonstrated that the hsa&#95;circ&#95;0046701/miR-142-3p/ITGB8 axis might play critical regulatory roles in the pathogenesis and development of glioma., (Copyright © 2018. Published by Elsevier Inc.)

Polycomb repressive complex 2 (PRC2) consists of three core subunits, EZH2, EED and SUZ12, and plays pivotal roles in transcriptional regulation. The catalytic subunit EZH2 methylates histone H3 lysine 27 (H3K27), and its activity is further enhanced by the binding of EED to trimethylated H3K27 (H3K27me3). Small-molecule inhibitors that compete with the cofactor S-adenosylmethionine (SAM) have been reported. Here we report the discovery of EED226, a potent and selective PRC2 inhibitor that directly binds to the H3K27me3 binding pocket of EED. EED226 induces a conformational change upon binding EED, leading to loss of PRC2 activity. EED226 shows similar activity to SAM-competitive inhibitors in blocking H3K27 methylation of PRC2 target genes and inducing regression of human lymphoma xenograft tumors. Interestingly, EED226 also effectively inhibits PRC2 containing a mutant EZH2 protein resistant to SAM-competitive inhibitors. Together, we show that EED226 inhibits PRC2 activity via an allosteric mechanism and offers an opportunity for treatment of PRC2-dependent cancers.

Polycomb repressive complex 2 (PRC2), a histone H3 lysine 27 methyltransferase, plays a key role in gene regulation and is a known epigenetics drug target for cancer therapy. The WD40 domain-containing protein EED is the regulatory subunit of PRC2. It binds to the tri-methylated lysine 27 of the histone H3 (H3K27me3), and through which stimulates the activity of PRC2 allosterically. Recently, we disclosed a novel PRC2 inhibitor EED226 which binds to the K27me3-pocket on EED and showed strong antitumor activity in xenograft mice model. Here, we further report the identification and validation of four other EED binders along with EED162, the parental compound of EED226. The crystal structures for all these five compounds in complex with EED revealed a common deep pocket induced by the binding of this diverse set of compounds. This pocket was created after significant conformational rearrangement of the aromatic cage residues (Y365, Y148 and F97) in the H3K27me3 binding pocket of EED, the width of which was delineated by the side chains of these rearranged residues. In addition, all five compounds interact with the Arg367 at the bottom of the pocket. Each compound also displays unique features in its interaction with EED, suggesting the dynamics of the H3K27me3 pocket in accommodating the binding of different compounds. Our results provide structural insights for rational design of novel EED binder for the inhibition of PRC2 complex activity., Competing Interests: L.Li, H.Z., M.Zhang., M.Zhao., Li.F., X.L., Z.G., Y.H., O.A., JH.Z., Y.L., H.F., Y.M., G.L., L.Liu., Le.F., F.L., L.T., W.Q., J.O., A.L., D.E. B., Z.Y., P.A.,C.L., E.L., J.G., and K.Z. are all employees of Novartis Institutes of BioMedical Research and may hold Novartis stock. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Objective: To explore the efficacy and safety of laparoscopic tunnel-like peri-anterior superior iliac spine suspension(L-TASISS) or combined with stapled transanal rectal resection (STARR) in the treatment of pelvic organ prolapse (POP) with outlet obstructive constipation (OOC)., Methods: A total of 119 POP patients complicated with OOC( II( to IIII( stage evaluated by POP-Q) received L-TASISS or combined with STARR in the First Affiliated Hospital of Zhengzhou University from August 2010 to January 2015. Clinical and follow-up data of these patients were analyzed retrospectively and compared before and after operation., Results: Among 119 cases, 51 cases(42.9%) underwent L-TASISS alone, and 68 cases (57.1%) received L-TASISS combined with STARR. All the 119 patients were successfully operated without conversion to open surgery. The operation time was (67.8±10.9) minutes, the intra-operative blood loss was (10.3±3.8) ml, the indwelling catheter time was (3.6±1.1) days, and hospital stay was (5.1±1.8) days. One month after operation, abdominal wall pain or stress occurred in 15 cases, of whom 3 cases were improved by local block injection, 1 case by incision stitches release, the rest ameliorated spontaneously within 3 months after surgery. No potential ureterostenosis, hydroureterosis, internal iliac vascular thrombosis resulting from compression of the mesh and other complications related to the mesh were found. One year after operation, all the patients were followed up. The OOC remission rate was 78.2%(93/119), of whom 76 cases were satisfied and 17 patients were completely satisfied. One case(0.8%) with stress urinary incontinence did not improve. Fifteen cases(12.6%) with algopareunia or dyspareunia did not achieve remission, but there was no new algopareunia or dyspareunia case. Eleven patients (9.2%) presented recurrence of symptoms, of whom 9 cases(7.6%) complained of sensation of incomplete evacuation. Two cases(1.7%) were graded as POP-Q II(, and 1 case (0.8%) as POP-Q III( after surgery. Constipation Score of all the patients was 1.4±0.9 (compared to 7.8±3.6 preoperatively) according to Rome III( criteria. Enterocele occurred in 53 cases (44.5%) preoperatively corresponded with only 1 case (0.8%) after operation (χ(2)=64.77, P=0.000). One hundred and six cases (86.6%) with defecation difficulties and 87 cases (73.1%) with sensation of incomplete evacuation before operation were significantly improved after surgery, corresponding with 7(5.9%) and 9 (7.6%) symptomatic cases respectively (χ(2)=155.78, P=0.000). Three cases (2.5%) with preoperative fecal incontinence symptoms were improved after operation as well., Conclusion: The procedure of L-TASISS or combined with STARR for POP patients with OCC has good short-term efficacy, and is safe and feasible.

Purpose To develop a three-dimensional breath-hold (BH) magnetic resonance (MR) cholangiopancreatographic protocol with sampling perfection with application-optimized contrast using different flip-angle evolutions (SPACE) acquisition and sparsity-based iterative reconstruction (SPARSE) of prospectively sampled 5% k-space data and to compare the results with conventional respiratory-triggered (RT) acquisition. Materials and Methods This HIPAA-compliant prospective study was institutional review board approved. Twenty-nine patients underwent conventional RT SPACE and BH-accelerated SPACE acquisition with 5% k-space sampling at 3 T. Spatial resolution and other parameters were matched when possible. BH SPACE images were reconstructed by enforcing joint multicoil sparsity in the wavelet domain (SPARSE-SPACE). Two board-certified radiologists independently evaluated BH SPARSE-SPACE and RT SPACE images for image quality parameters in the pancreatic duct and common bile duct by using a five-point scale. The Wilcoxon signed-rank test was used to compare BH SPARSE-SPACE and RT SPACE images. Results Acquisition time for BH SPARSE-SPACE was 20 seconds, which was significantly (P < .001) shorter than that for RT SPACE (mean ± standard deviation, 338.8 sec ± 69.1). Overall image quality scores were higher for BH SPARSE-SPACE than for RT SPACE images for both readers for the proximal, middle, and distal pancreatic duct, but the difference was not statistically significant (P > .05). For reader 1, distal common bile duct scores were significantly higher with BH SPARSE-SPACE acquisition (P = .036). More patients had acceptable or better overall image quality (scores ≥ 3) with BH SPARSE-SPACE than with RT SPACE acquisition, respectively, for the proximal (23 of 29 [79%] vs 22 of 29 [76%]), middle (22 of 29 [76%] vs 18 of 29 [62%]), and distal (20 of 29 [69%] vs 13 of 29 [45%]) pancreatic duct and the proximal (25 of 28 [89%] vs 22 of 28 [79%]) and distal (25 of 28 [89%] vs 24 of 28 [86%]) common bile duct. Conclusion BH SPARSE-SPACE showed similar or superior image quality for the pancreatic and common duct compared with that of RT SPACE despite 17-fold shorter acquisition time. (©) RSNA, 2016.

Background: Astragalus membranaceus Bge. var. mongolicus (Bge.) Hsiao (A. mongolicus) is an important traditional Chinese herb that is cultivated on a large scale in northwestern China. Understanding plant responses to drought has important effects on ecological environment recovery and local economic development. Here, we combined transcriptomics (Illumina Hiseq 2000) and metabolomics ((1)H-NMR) to investigate how the roots of two-year-old A. mongolicus responded to 14 days of progressive drought stress., Results: The dried soil reduced the relative water content (RWC) of the leaves and biomass, induced the differential expression of a large fraction of the transcriptome and significantly altered the metabolic processes. PCA analysis demonstrated that the sucrose, proline, and malate metabolites contributed greatly to the separation. Strikingly, proline was increased by almost 60-fold under severe stress compared to the control. Some backbone pathways, including glycolysis, tricarboxylic acid (TCA) cycle, glutamate-mediated proline biosynthesis, aspartate family metabolism and starch and sucrose metabolism, were significantly affected by drought. An integrated analysis of the interaction between key genes and the altered metabolites involved in these pathways was performed., Conclusions: Our findings demonstrated that the expression of drought-responsive genes showed a strong stress-dose dependency. Analysis of backbone pathways of the transcriptome and metabolome revealed specific genotypic responses to different levels of drought. The variation in molecular strategies to the drought may play an important role in how A. mongolicus and other legume crops adapt to drought stress.

Object: We aimed to demonstrate that follow-up scans in longitudinal examinations can be significantly accelerated by using images from previous scans as priors for constrained reconstruction., Materials and Methods: In this work, we propose a method for incorporating a prior image to improve the reconstruction of a new acquisition with considerable k-space undersampling, which contains a two-level registration scheme with non-parametric transformation, an adaptive synthesis procedure, and a constrained reconstruction with weighted total variation constraint. The performance of the method is evaluated using simulations, as well as results from volunteer and patient examinations., Results: In vivo experiments with both volunteers and patients show that incorporating a prior image into the constrained reconstruction produces many fewer reconstruction errors compared to the conventional reconstruction using only the highly undersampled k-space data., Conclusion: The redundant information in the prior image can be efficiently adopted to improve the reconstruction quality of the new acquisition. When maintaining the image quality, higher acceleration can be achieved with the incorporation of the prior image.