Myosin-binding protein 13 mediates primary seed dormancy via abscisic acid biosynthesis and signaling in Arabidopsis.

Dormancy is an essential characteristic that enables seeds to survive in unfavorable conditions while germinating when conditions are favorable. Myosin-binding proteins (MyoBs) assist in the movement of organelles along actin microfilaments by attaching to both organelles and myosins. In contrast to studies on yeast and metazoans, research on plant MyoBs is still in its early stages and primarily focuses on tip-growing cells. In this study, we found that Arabidopsis MyoB13 is highly expressed in dry mature seeds. The myob13 mutant, created using CRISPR/Cas9, exhibits a preharvest sprouting phenotype, which can be mitigated by after-ripening treatment, indicating that MyoB13 plays a positive role in primary seed dormancy. Furthermore, we show that MyoB13 negatively regulates ABA biosynthesis and signaling pathways. Notably, the expression of MyoB13 orthologs from maize and soybean can completely restore the phenotype of the Arabidopsis myob13 mutant, suggesting that the function of MyoB13 in ABA-induced seed dormancy is evolutionarily conserved. Therefore, the functional characterization of MyoB13 offers an additional genetic resource to help prevent vivipary in crop species.

HILPDA-mediated lipidomic remodelling promotes radiotherapy resistance in nasopharyngeal carcinoma by accelerating mitophagy.

Radiotherapy resistance is a major obstacle to nasopharyngeal carcinoma (NPC) therapy and contributes to tumour recurrence and metastasis. Lipid metabolism is a key regulatory mechanism in cancer biology; however, its role in NPC radiotherapy resistance remains unclear. In this study, we identified hypoxia-inducible lipid droplet-associated protein (HILPDA) as a newly discovered regulator of radioresistance that induces not only lipid droplet (LD) formation but also intracellular lipid remodelling, notably changing mitochondrial cardiolipin (CL) levels. Additionally, we found that the upregulation of CL promotes mitophagy in response to irradiation exposure. Mechanistically, HILPDA inhibits PINK1-mediated CLS1 ubiquitination and degradation. The combination of a mitophagy inhibitor and irradiation significantly increases the radiosensitivity of NPC cells. Human cancer-derived data confirmed that the HILPDA-CLS1 pathway promotes NPC radioresistance. Collectively, these findings suggest that HILPDA plays a critical role in promoting NPC radioresistance and might be targeted to overcome radiotherapeutic resistance in NPC patients in the clinic.

Repeatability assessment of anterior segment measurements in myopic patients using an anterior segment OCT with placido corneal topography and agreement with a swept-source OCT.

BACKGROUND: The precision of anterior segment biometric measurements in eyes has become increasingly important in refractive surgery. The purpose of this study is to assess the repeatability of the automatic measurements provided by a new spectral-domain optical coherence tomograph (SD-OCT)/Placido topographer (MS-39, CSO) and its agreement with a swept-source OCT (SS-OCT) biometer (CASIA SS-1000, Tomey) in patients with myopia. METHODS: The right eye of 235 subjects was scanned 3 times with both devices. The evaluated parameters included central corneal radius of the steep meridian, central corneal radius of the flat meridian, mean central corneal radius, thinnest corneal thickness, central corneal thickness, anterior chamber depth, corneal volume and diameter. The intraobserver repeatability of the MS-39 measurements was calculated using intraclass correlation coefficient (ICC), within subject standard deviation, coefficient of repeatability, coefficient of variation and repeated-measures analysis of variance of the 3 repeated measurements. The agreement between the two devices was evaluated by 95% limits of agreement (LoA). RESULTS: The majority of the parameters acquired from MS-39 showed high repeatability. The repeatability of corneal diameter was slightly lower than the other measurements, although the ICC remained high. Agreement with the CASIA SS-1000 was good, indicated by the Bland-Altman plots with narrow 95% LoA values for all parameters assessed. CONCLUSIONS: The high repeatability of automatic measurements by the new device supports its clinical application in eyes with myopia, and the good agreement between the two devices indicates they could be used interchangeably for the parameters evaluated.

NHC-Catalyzed Chemoselective Reactions of Enals and Cyclopropylcarbaldehydes for Access to Chiral Dihydropyranone Derivatives.

An N-heterocyclic carbene (NHC)-catalyzed chemoselective activation reaction of 1-cyclopropylcarbaldehydes and α-alkynyl enals is reported. NHC selectively catalyzes 1-cyclopropylaldehydes, followed by a [2 + 4] cycloaddition reaction with α-alkynyl enals. The target dihydropyranone derivatives bearing different substituents and substitution patterns can be obtained in good to excellent yields with excellent enantio- and diastereoselectivities under mild conditions.

Algorithms for Designing Unimodular Sequences with High Doppler Tolerance for Simultaneous Fully Polarimetric Radar.

Simultaneous fully polarimetric radar uses orthogonal polarization channels to transmit a pair of signals, both of which must have good auto- and cross-correlation characteristics. In this paper, the design of sequences with good correlation properties and Doppler tolerance is investigated. New cyclic algorithms, namely, Cyclic Algorithm-Gradient I (CAGI) and Cyclic Algorithm-Gradient II (CAGII) are proposed to solve the optimization problem. Meanwhile, the sequences designed in this paper have ultra-low auto- and cross-correlation side-lobes in a specified lag interval. Numerical experiments are conducted to demonstrate and validate the superiority of the proposed cyclic algorithms, especially for the measurement of moving targets.

A Method for Estimating the Polarimetric Scattering Matrix of Moving Target for Simultaneous Fully Polarimetric Radar.

To precisely obtain the polarimetric scattering matrix (PSM) of moving target, a measurement model for the simultaneous fully polarimetric radar is formulated. The calibration errors and isolation of the transmitted waveforms are considered. To address the decline in performance of the traditional PSM estimation methods when the target moves, a novel method with measurement selection is proposed. Numerical experiments are conducted to demonstrate and validate the superiority of the proposed method, especially for the PSM estimation of the target with non-uniform motion.

Gene expression profiling of venous malformations identifies the role of SDC1 in venous endothelial cells.

Objective: To obtain insight into the molecular process implicated in venous malformations (VMs) and identify potential targets for treatment of VMs, this study profiled the gene expression pattern in VMs, investigated alterations of syndecan-1 (SDC1) expression in VMs, and tested the hypothesis that aberrant SDC1 expression triggers abnormal angiogenesis and VM development. Methods: Microarray analysis was performed to identify differentially expressed genes (DEGs) on a transcriptome-wide level in VMs and conjunctive normal. Gene Ontology molecular functional analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis were carried out to establish enhancement of biological signaling pathways involved in VMs. Among the DEGs, we focused on SDC1, which is involved in matrix remodeling, cell proliferation and invasion, and angiogenesis. SDC1 expression in VMs was verified by qRT-PCR, western blotting, and immunohistochemistry. Loss-of-function of SDC1 was achieved in human umbilical vein endothelial cells (HUVECs) by siRNA to investigate the roles of SDC1 in cell migration, invasion, and angiogenesis. Results: Compared with control tissue, the transcriptome study identified 274 upregulated DEGs and 3 downregulated DEGs. The transcript and protein levels of SDC1 were significantly decreased in VMs compared with normal tissue. Inhibition of SDC1 enhanced HUVEC migration, invasion, and angiogenesis. Conclusion: Our genome-wide microarray analysis suggests the involvement of numerous genes in VMs. Among them, SDC1 plays a substantial role in the process of angiogenesis and development of VMs. SDC1 may represent a potential target for a molecular therapy for VMs.

Understanding the role of pathways in a deep neural network.

Deep neural networks have demonstrated superior performance in artificial intelligence applications, but the opaqueness of their inner working mechanism is one major drawback in their application. The prevailing unit-based interpretation is a statistical observation of stimulus-response data, which fails to show a detailed internal process of inherent mechanisms of neural networks. In this work, we analyze a convolutional neural network (CNN) trained in the classification task and present an algorithm to extract the diffusion pathways of individual pixels to identify the locations of pixels in an input image associated with object classes. The pathways allow us to test the causal components which are important for classification and the pathway-based representations are clearly distinguishable between categories. We find that the few largest pathways of an individual pixel from an image tend to cross the feature maps in each layer that is important for classification. And the large pathways of images of the same category are more consistent in their trends than those of different categories. We also apply the pathways to understanding adversarial attacks, object completion, and movement perception. Further, the total number of pathways on feature maps in all layers can clearly discriminate the original, deformed, and target samples.

IIAM: Intra and Inter Attention With Mutual Consistency Learning Network for Medical Image Segmentation.

Medical image segmentation provides a reliable basis for diagnosis analysis and disease treatment by capturing the global and local features of the target region. To learn global features, convolutional neural networks are replaced with pure transformers, or transformer layers are stacked at the deepest layers of convolutional neural networks. Nevertheless, they are deficient in exploring local-global cues at each scale and the interaction among consensual regions in multiple scales, hindering the learning about the changes in size, shape, and position of target objects. To cope with these defects, we propose a novel Intra and Inter Attention with Mutual Consistency Learning Network (IIAM). Concretely, we design an intra attention module to aggregate the CNN-based local features and transformer-based global information on each scale. In addition, to capture the interaction among consensual regions in multiple scales, we devise an inter attention module to explore the cross-scale dependency of the object and its surroundings. Moreover, to reduce the impact of blurred regions in medical images on the final segmentation results, we introduce multiple decoders to estimate the model uncertainty, where we adopt a mutual consistency learning strategy to minimize the output discrepancy during the end-to-end training and weight the outputs of the three decoders as the final segmentation result. Extensive experiments on three benchmark datasets verify the efficacy of our method and demonstrate superior performance of our model to state-of-the-art techniques.

Design, Synthesis, and Herbicidal Evaluation of Pyrrolidinone-Containing 2-Phenylpyridine Derivatives as Novel Protoporphyrinogen Oxidase Inhibitors.

In this work, a series of pyrrolidinone-containing 2-phenylpyridine derivatives were synthesized and evaluated as novel protoporphyrinogen IX oxidase (PPO, EC 1.3.3.4) inhibitors for herbicide development. At 150 g ai/ha, compounds 4d, 4f, and 4l can inhibit the grassy weeds of Echinochloa crus-galli (EC), Digitaria sanguinalis (DS), and Lolium perenne (LP) with a range of 60 to 90%. Remarkably, at 9.375 g ai/ha, these compounds showed 100% inhibition effects against broadleaf weeds of Amaranthus retroflexus (AR) and Abutilon theophrasti (AT), which were comparable to the performance of the commercial herbicides flumioxazin (FLU) and saflufenacil (SAF) and better than that of acifluorfen (ACI). Molecular docking analyses revealed significant hydrogen bonding and π-π stacking interactions between compounds 4d and 4l with Arg98, Asn67, and Phe392, respectively. Additionally, representative compounds were chosen for in vivo assessment of PPO inhibitory activity, with compounds 4d, 4f, and 4l demonstrating excellent inhibitory effects. Notably, compounds 4d and 4l induced the accumulation of reactive oxygen species (ROS) and a reduction in the chlorophyll (Chl) content. Consequently, compounds 4d, 4f, and 4l are promising lead candidates for the development of novel PPO herbicides.

Discovery of Pyridyl-Benzothiazol Hybrids as Novel Protoporphyrinogen Oxidase Inhibitors via Scaffold Hopping.

In order to discover novel protoporphyrinogen oxidase (PPO) inhibitors with excellent herbicidal activity, a series of structurally novel 6-(pyridin-2-yl) benzothiazole derivatives were designed based on the scaffold hopping strategy. The in vitro experiments demonstrated that the newly synthesized compounds exhibited noteworthy inhibitory activity against Arabidopsis thaliana PPO (AtPPO), with IC50 values ranging from 0.06 to 1.36 µM. Preliminary postemergence herbicidal activity tests and crop safety studies indicated that some of our compounds exhibited excellent herbicidal activity and crop safety. For instance, compound (rac)-7as exhibited superior herbicidal activities to commercially available flumioxazin (FLU) and saflufenacil (SAF) at all the tested concentrations and showed effective herbicidal activities even at a dosage as low as 18.75 g ai/ha. Meanwhile, compound (rac)-7as showed good crop safety for wheat at a dosage as high as 150 g of ai/ha. Although the absolute configuration of compound 7as has no obvious effect on its herbicidal activity, compound (R)-7as showed a slightly higher crop safety than compound (S)-7as. Molecular simulation studies of Nicotiana tabacum PPO (NtPPO) and our candidate compounds showed that the benzothiazole moiety of compounds (R)-7as or (S)-7as formed multiple π-π stacking interactions with FAD, and the pyridine ring generated π-π stacking with Phe-392. Our finding proved that the pyridyl-benzothiazol hybrids are promising scaffolds for the development of PPO-inhibiting herbicides.

Self-Adaptive Graph With Nonlocal Attention Network for Skeleton-Based Action Recognition.

Graph convolutional networks (GCNs) have achieved encouraging progress in modeling human body skeletons as spatial-temporal graphs. However, existing methods still suffer from two inherent drawbacks. Firstly, these models process the input data based on the physical structure of the human body, which leads to some latent correlations among joints being ignored. Furthermore, the key temporal relationships between nonadjacent frames are overlooked, preventing to fully learn the changes of the body joints along the temporal dimension. To address these issues, we propose an innovative spatial-temporal model by introducing a self-adaptive GCN (SAGCN) with global attention network, collectively termed SAGGAN. Specifically, the SAGCN module is proposed to construct two additional dynamic topological graphs to learn the common characteristics of all data and represent a unique pattern for each sample, respectively. Meanwhile, the global attention module (spatial attention (SA) and temporal attention (TA) modules) is designed to extract the global connections between different joints in a single frame and model temporal relationships between adjacent and nonadjacent frames in temporal sequences. In this manner, our network can capture richer features of actions for accurate action recognition and overcome the defect of the standard graph convolution. Extensive experiments on three benchmark datasets (NTU-60, NTU-120, and Kinetics) have demonstrated the superiority of our proposed method.

Herbicidal Activity of Beflubutamid Analogues as PDS Inhibitors and SAR Analysis and Degradation Dynamics in Wheat.

In this work, a series of beflubutamid (BF) analogues' postemergent herbicidal activity was evaluated, and the structure-activity relationship (SAR) was discussed. At a dosage of 300 g ai/ha, compounds (Rac)-6h and (Rac)-6q showed excellent herbicidal activity against Amaranthus retroflexus, Abutilon theophrasti, and Medicago sativa, with inhibition rates of 90, 100, and 80% and 100, 100, and 100%, respectively, comparable to that of commercial herbicide BF, which showed inhibition rates of 90, 100, and 100%, respectively. Notably, at dosages of 150 and 300 g ai/ha, the chiral compounds (S)-6h and (S)-6q exhibited higher herbicidal activities than their racemates. Molecular docking results indicated that compounds (S)-BF and (S)-6h have stronger binding affinities with Oryza sativa phytoene desaturase (OsPDS), resulting in a higher herbicidal activity. Additionally, the degradation dynamics half-life of (S)-BF in wheat was determined to be 77.02 h. Consequently, compounds (S)-6h and (S)-6q are promising lead candidates for the development of highly effective herbicides.

Structure-activity relationship and biological evaluation of xanthine derivatives as PCSK9 inhibitors for the treatment of atherosclerosis.

Developing non-statin small molecules for the treatment of hypercholesterolemia remains challenging. The proprotein convertase subtilisin/kexin type 9 (PCSK9)-targeted therapies have attracted considerable attentions. Forty-five 7030B-C5 derivatives were synthesized and evaluated for the PCSK9 repression activity, taking the PCSK9 transcriptional inhibitor 7030B-C5 as the lead. Structure-activity relationship (SAR) analysis at C8 and N7-position was carried out, and compound 3s and 5r exhibited comparable PCSK9 transcriptional inhibitory activity but much lower cytotoxicity with the therapeutic index (TI) values doubled of that of 7030B-C5. In the in vitro assay, both compounds significantly reduced the level of PCSK9 protein and increased LDL receptor (LDLR) protein level. What's more, both compounds promoted LDL cholesterol (LDL-C) clearance more efficiently than 7030B-C5 in HepG2 cells. Most importantly, compound 3s reduced the atherosclerotic plaque areas with promising lipid-lowing effects in ApoE KO mice with a higher in vivo activity and lower toxicity. The regulatory mechanism of 3s was explored that it might target the transcription factor HNF1α and/or HINFP upstream of PCSK9 transcription, similar to that of 7030B-C5. Thus, 3s was considered as a potential anti-atherosclerosis drug candidate as a novel PCSK9 down-regulatory agent, worthy of further investigations.

[Mutation in the UBIAD1 gene of a Chinese family with Schnyder crystal corneal dystrophy].

OBJECTIVE: To investigate the genetic feature of Schnyder corneal dystrophy identified in a four-generation Chinese family. METHOD: Ophthalmologic examinations were performed in 3 affected members and 2 unaffected members of a family with Schnyder corneal dystrophy and controls. Genomic DNA was extracted from peripheral blood. The coding regions, 3'UTR and 5'UTR of UBIAD1 gene from all samples were screened by polymerase chain reaction (PCR) and direct DNA sequencing using the primers designed according to the sequence of UBIAD1, and comparatively analyzed with data from Genebank. RESULT: The family has 15 members over 4 generations with similar signs and symptoms among proband and affected members. All affected members of the family demonstrated central discoid crystalline deposition with arcus lipoide. Confocal microscopy examination showed multiple depositions of crystalline materials in anterior stroma. OCT showed the high reflective material localized within the anterior stroma. A missense mutation c.305A > G in 1 exon of UBIAD1 gene resulting in a substitution of Asparagine to Serine at codon 102 (p.Asn102Ser) was found in all affected members of the family who were clinically diagnosed as Schnyder corneal dystrophy while not in the unaffected members of the family and controls. CONCLUSION: The missense mutation c.305A > G(p.Asn102Ser) of UBIAD1 gene may cause the disease of the family. Gene screen can assist clinicians in making definitive diagnosis, presymptomatic diagnosis and prenatal diagnosis.

[The investigation of microbial culturing of microkeratome blades and sponges used in laser in situ keratomileusis].

OBJECTIVE: The microbial culturing results were analysed from samples of the microkeratome blade and sponges in laser in situ keratomileusis (LASIK) procedures as for crossing the rational antibiotic eye drops for preventing infectious keratitis. METHOD: In this prospective study, 106 microkeratome blades and 212 sponges were cultured in routine LASIK procedure, at Excimer laser center in Henan Eye Institute During March to April 2009. Positive cultures were then sent for routine sensitivities and the results were analysed. RESULTS: 8 of the 106 blades were culturing positive, the positive rate was 7.55%. Each four positive cultures were in male and female patients. There was no statistical difference with gender (P = 1.000). 23 of the 212 sponges cultures were positive. The positive rate was 10.38%. All positive cultures grew Staphylococcus epidermidis. Twelve sponge positive cultures were in right eye and 11 were in left eye. There was no statistical difference between the right eye and left eye (P = 0.825). All of the 31 positive cultures were sensitive to gatifloxacin. The sensitivity of gatifloxacin, tobramycin, levofloxacin, ofloxacin, and ciprofloxacin were 100.00%, 96.77% (30/31), 93.55% (29/31), 90.32% (28/31) and 74.20% (23/31) respectively. All the patients have no infectious keratitis followed-up more then 6 monthes. CONCLUSION: There could be positive cultures from samples of the microkeratome blade and sponges in routine LASIK procedures but no patients with positive cultures developed postoperative infectious keratitis. The main positive bacteria was Staphylococcus epidermidis. They are sensitive to third and the fourth-generation fluoroquinolones and tobramycin antibiotics. Pre and post-operative supply of sensitive antibiotics can prevent post-operative infection.

[The clinical analysis of corneal interface fluid syndrome].

OBJECTIVE: To analysis the clinical characteristics of corneal interface fluid syndrome (IFS). METHODS: This is a retrospective study. During Jun. 2007 to Oct. 2011. Eight cases (12 eyes) of IFS were diagnosed at Henan Eye Institute. The history and complete ophthalmic examination that include Slit-lamp examination, Slit-lamp photography, IOP, anterior segment OCT (AS-OCT), confocal microscopic exams were recorded. RESULTS: In total 8 cases (12 eyes), 4 cases were bilateral, 4 cases were unilateral. Six patients were male and 2 were female. The age of the patients ranged from 19 to 35 years. Post-lasik steroid-induced elevated IOP was 4 eyes in 2 patients. Primary open angle glaucoma was 4 eyes in 2 patients. 1 patient (1 eye) was Posner-Shlossman syndrome, 1 patient (1 eye) was pigmented glaucoma, 1 patient (1 eye) was post-lasik traumatic iritis. 1 patient (1 eye) got IFS after repeated flap reposition because of epithelium ingrowth. Slit-lamp exam indicated edematous corneal, lamellar haze, interface fluids accumulation. AS-OCT showed obvious interface dark area. Confocal microscopy exam showed edematous corneal flap, more oval and large keratocytes' nuclei but no inflammatory cells. CONCLUSIONS: IFS is a rare but serious complication after LASIK. The main causes are high intraocular pressure and/or dysfunction of corneal endothelium. Careful exam by slit-lamp may help diagnosis, and further AS-OCT and/or in vivo confocal microscopy exam will confirm it.

Application Potential of CTHRC1 as a Diagnostic and Prognostic Indicator for Colon Adenocarcinoma.

Colon adenocarcinoma (COAD), ranking third in incidence and second in mortality, is one of the most common cancer types in the world. The initial stages of COAD usually show no obvious clinical symptoms; moreover, effective screening or diagnostic indicators with high sensitivity and specificity are lacking, which often leads to missed treatment opportunities. Collagen triple helix repeat containing 1 (CTHRC1) is a glycosylated protein secreted during tissue repair, which reduces collagen matrix deposition and promotes cell migration. Under physiological conditions, the expression of CTHRC1 is conducive to wound healing; however, the pathological overexpression of CTHRC1 promotes tumour growth and proliferation. In this study, we evaluated the application potential of CTHRC1 as an early diagnosis and prognostic survival monitoring biomarker for COAD in addition to unravelling its molecular mechanism in the development of COAD and exploring new therapeutic targets. Therefore, various tumour databases were used to investigate the expression of CTHRC1 in COAD at the mRNA and protein levels. CTHRC1 expression was found to be significantly increased in COAD, regardless of clinical cancer stage, age, sex or race. Moreover, CTHRC1 expression was significantly correlated with poor prognosis and positively correlated with CD8+ T cell, CD4+ T cell, neutrophil, macrophage and dendritic cell infiltration. The relevant function pathways and neighbouring proteins to CTHRC1 in COAD were identified as ROR2, VAPA, LY6E and several collagen family proteins. Therefore, this study suggests that CTHRC1 is a potential diagnostic and prognostic biomarker for patients with COAD.

Bacterial Keratitis Following Small Incision Lenticule Extraction.

Purpose: To describe the development of bacterial keratitis after small incision lenticule extraction in 5 patients and to explore its appropriate therapies. Methods: We retrospectively summarized the clinical treatments of five patients with postoperative bacterial infection after small incision lenticule extraction, who were referred to our hospital from 2019 to 2021. Results: Five male patients had undergone bilateral SMILE in the local hospital due to myopia aged from 18 to 26 years. The onset of keratitis during 1-3 days postoperatively and four of them were severe infection (2 bilateral, 2 unilateral). In five cases, 1 patient (1 eye) who was infected mild keratitis after SMILE was treated with only topical antibiotics; the others who respond poorly to topical antibiotics require surgical treatment, which 1 patient (1 eye) infected necrotic mass of the corneal cap was scraped and irrigated with antibiotic, and 3 patients (5 eyes) were treated by converting the cap to flap, curetting the necrotic tissue and irrigating with the antibiotic solution. In all patients, the duration from onset to resolution was 1-5 weeks. The final uncorrected visual acuity was above 20/32. Conclusion: Owing to the upward popularity of refractive surgery, the incidence of keratitis after SMILE should not be ignored. Early diagnosis and timely treatment of post-SMILE keratitis are essential. For severe keratitis that fails to respond to topical antibiotics, the corneal cap should be opened as a flap.

Arabidopsis RAN GTPases are critical for mitosis during male and female gametogenesis.

The development of male and female gametophytes is a prerequisite for successful propagation of angiosperms. The small GTPases RAN play fundamental roles in numerous cellular processes. Although RAN GTPases have been characterized in plants, their roles in cellular processes are far from understood. We report here that RAN GTPases in Arabidopsis are critical for gametophytic development. RAN1 loss-of-function showed no defects in gametophytic development likely due to redundancy. However, the expression of a dominant negative or constitutively active RAN1 resulted in gametophytic lethality. Genetic interference of RAN GTPases caused the arrest of pollen mitosis I and of mitosis of functional megaspores, implying a key role of properly regulated RAN activity in mitosis during gametophytic development.