Interference with GPR4 inactivates NLRP3 inflammasome signaling by inhibiting LPAR1 expression to ameliorate oxygen-glucose deprivation/reoxygenation-induced inflammation and apoptosis of cardiomyocytes.

Myocardial ischemia/reperfusion (MI/R) injury is a detrimental disease with high mortality worldwide. We aimed to explore the role of G protein-coupled receptor 4 (GPR4) and lysophosphatidic acid receptor 1 (LPAR1) in MI/R injury in vitro. H9c2 cells were exposed to oxygen-glucose deprivation/reoxygenation (OGD/R) conditions to simulate the MI/R injury and GPR4 expression was detected. Then, GPR4 was knocked down and cell viability was examined with a CCK-8 assay. The activities of LDH, CK and CK-MB were detected to evaluate the damage of OGD/R-induced H9c2 cells. ELISA kits and TUNEL staining were used to examine the inflammation and apoptosis of H9c2 cells exposed to OGD/R conditions. Western blot was employed to detect the expression of proteins related to apoptosis and NLRP3 inflammasome signaling. Additionally, Co-IP analyzed the binding between GPR4 and LPAR1. Finally, LPAR1 was overexpressed to conduct the rescue experiments. Results revealed that GPR4 was upregulated in OGD/R-treated H9c2 cells and GPR4 knockdown attenuated the damage of H9c2 cells. OGD/R induced inflammation and apoptosis were markedly inhibited by GPR4 silencing, as evidenced by the decreased TNF-α, IL-6 and IL-8 levels as well as the elevated Bcl-2 expression and reduced Bax and cleaved caspase3 expression. Moreover, GPR4 bound to LPAR1 and upregulated LPAR1 expression. Interference with GPR4 inactivated the NLRP3 inflammasome signaling. Besides, LPAR1 overexpression abrogated the effects of GPR4 silencing on the damage, inflammation and apoptosis of H9c2 cells induced by OGD/R. Particularly, LPAR1 upregulation promoted the activation of NLRP3 inflammasome signaling in GPR4-silenced H9c2 cells induced by OGD/R. To be concluded, GPR4 deficiency inactivates NLRP3 inflammasome signaling by inhibiting LPAR1 expression to ameliorate OGD/R -induced inflammation and apoptosis of cardiomyocytes.

Application of artificial intelligence-based dual-modality analysis combining fundus photography and optical coherence tomography in diabetic retinopathy screening in a community hospital.

BACKGROUND: To assess the feasibility and clinical utility of artificial intelligence (AI)-based screening for diabetic retinopathy (DR) and macular edema (ME) by combining fundus photos and optical coherence tomography (OCT) images in a community hospital. METHODS: Fundus photos and OCT images were taken for 600 diabetic patients in a community hospital. Ophthalmologists graded these fundus photos according to the International Clinical Diabetic Retinopathy (ICDR) Severity Scale as the ground truth. Two existing trained AI models were used to automatically classify the fundus images into DR grades according to ICDR, and to detect concomitant ME from OCT images, respectively. The criteria for referral were DR grades 2-4 and/or the presence of ME. The sensitivity and specificity of AI grading were evaluated. The number of referable DR cases confirmed by ophthalmologists and AI was calculated, respectively. RESULTS: DR was detected in 81 (13.5%) participants by ophthalmologists and in 94 (15.6%) by AI, and 45 (7.5%) and 53 (8.8%) participants were diagnosed with referable DR by ophthalmologists and by AI, respectively. The sensitivity, specificity and area under the curve (AUC) of AI for detecting DR were 91.67%, 96.92% and 0.944, respectively. For detecting referable DR, the sensitivity, specificity and AUC of AI were 97.78%, 98.38% and 0.981, respectively. ME was detected from OCT images in 49 (8.2%) participants by ophthalmologists and in 57 (9.5%) by AI, and the sensitivity, specificity and AUC of AI were 91.30%, 97.46% and 0.944, respectively. When combining fundus photos and OCT images, the number of referrals identified by ophthalmologists increased from 45 to 75 and from 53 to 85 by AI. CONCLUSION: AI-based DR screening has high sensitivity and specificity and may feasibly improve the referral rate of community DR.

Oct1/Pou2f1 is selectively required for colon regeneration and regulates colon malignancy.

The transcription factor Oct1/Pou2f1 promotes poised gene expression states, mitotic stability, glycolytic metabolism and other characteristics of stem cell potency. To determine the effect of Oct1 loss on stem cell maintenance and malignancy, we deleted Oct1 in two different mouse gut stem cell compartments. Oct1 deletion preserved homeostasis in vivo and the ability to establish organoids in vitro, but blocked the ability to recover from treatment with dextran sodium sulfate, and the ability to maintain organoids after passage. In a chemical model of colon cancer, loss of Oct1 in the colon severely restricted tumorigenicity. In contrast, loss of one or both Oct1 alleles progressively increased tumor burden in a colon cancer model driven by loss-of-heterozygosity of the tumor suppressor gene Apc. The different outcomes are consistent with prior findings that Oct1 promotes mitotic stability, and consistent with differentially expressed genes between the two models. Oct1 ChIPseq using HCT116 colon carcinoma cells identifies target genes associated with mitotic stability, metabolism, stress response and malignancy. This set of gene targets overlaps significantly with genes differentially expressed in the two tumor models. These results reveal that Oct1 is selectively required for recovery after colon damage, and that Oct1 has potent effects in colon malignancy, with outcome (pro-oncogenic or tumor suppressive) dictated by tumor etiology.

Constructing 3D Interconnected Si/SiOx /C Nanorings from Polyhedral Oligomeric Silsesquioxane.

Polyhedral oligomeric silsesquioxane (POSS) is a family of organic/inorganic hybrid materials with specific molecular symmetry, and shows great potential in the structural design of nanomaterials. Here, a "bottom-up" strategy is designed to fabricate 3D interconnected Si/SiOx /C nanorings (NRs) via AlCl3 -assisted aluminothermic reduction using dodecaphenyl cage silsesquioxane (T12 -Ph) as the building block. In this process, AlCl3 acts as both a liquid medium for reduction, and significantly as the catalyst to the cross-linking of phenyl groups in T12 -Ph. The obtained Si/SiOx /C NRs exhibits uniform diameter of ≈165 nm and well distribution of C and Si elements. The unique ring-like structure of Si/SiOx /C NRs makes it have great application potential in the field of lithium ion batteries. Notably, Si/SiOx /C NRs exhibits superior high-rate capacity and good cycle stability when used as anode for LIBs. More excitingly, Si/SiOx /C NRs can deliver a high reversible capacity of 517.9 mA h g-1 at ultra-low temperature of -70 °C, and the capacity retention as high as ≈50% of that at 25 °C. This work not only broadens structural design of carbon-based nanomaterials but also provides more possibilities for the application of POSS.

Real-time Prediction of the Daily Incidence of COVID-19 in 215 Countries and Territories Using Machine Learning: Model Development and Validation.

BACKGROUND: Advanced prediction of the daily incidence of COVID-19 can aid policy making on the prevention of disease spread, which can profoundly affect people's livelihood. In previous studies, predictions were investigated for single or several countries and territories. OBJECTIVE: We aimed to develop models that can be applied for real-time prediction of COVID-19 activity in all individual countries and territories worldwide. METHODS: Data of the previous daily incidence and infoveillance data (search volume data via Google Trends) from 215 individual countries and territories were collected. A random forest regression algorithm was used to train models to predict the daily new confirmed cases 7 days ahead. Several methods were used to optimize the models, including clustering the countries and territories, selecting features according to the importance scores, performing multiple-step forecasting, and upgrading the models at regular intervals. The performance of the models was assessed using the mean absolute error (MAE), root mean square error (RMSE), Pearson correlation coefficient, and Spearman correlation coefficient. RESULTS: Our models can accurately predict the daily new confirmed cases of COVID-19 in most countries and territories. Of the 215 countries and territories under study, 198 (92.1%) had MAEs <10 and 187 (87.0%) had Pearson correlation coefficients >0.8. For the 215 countries and territories, the mean MAE was 5.42 (range 0.26-15.32), the mean RMSE was 9.27 (range 1.81-24.40), the mean Pearson correlation coefficient was 0.89 (range 0.08-0.99), and the mean Spearman correlation coefficient was 0.84 (range 0.2-1.00). CONCLUSIONS: By integrating previous incidence and Google Trends data, our machine learning algorithm was able to predict the incidence of COVID-19 in most individual countries and territories accurately 7 days ahead.

Emergence of a Radical-Stabilizing Metal-Organic Framework as a Radio-photoluminescence Dosimeter.

Radio-photoluminescence (RPL) materials display a distinct radiation-induced permanent luminescence center, and therefore find application in the detection of ionizing radiation. The current inventory of RPL materials, which were discovered by serendipity, has been limited to a small number of metal-ion-doped inorganic materials. Here we document the RPL of a metal-organic framework (MOF) for the first time: X-ray induced free radicals are accumulated on the organic linker and are subsequently stabilized in the conjugated fragment in the structure, while the metal center acts as the X-ray attenuator. These radicals afford new emission features in both UV-excited and X-ray excited luminescence spectra, making it possible to establish linear relationships between the radiation dose and the normalized intensity of the new emission feature. The MOF-based RPL materials exhibit advantages in terms of the dose detection range, reusability, emission stability, and energy threshold. Based on a comprehensive electronic structure and energy diagram study, the rational design and a substantial expansion of candidate RPL materials can be anticipated.

EFFECT OF OPTIC DISK-FOVEA DISTANCE ON MEASUREMENTS OF INDIVIDUAL MACULAR INTRARETINAL LAYERS IN NORMAL SUBJECTS.

PURPOSE: To investigate the effect of optic disk-fovea distance (DFD) on measurements of macular intraretinal layers using spectral domain optical coherence tomography in normal subjects. METHODS: One hundred and eighty-two eyes from 182 normal subjects were imaged using spectral domain optical coherence tomography. The average thicknesses of eight macular intraretinal layers were measured using an automatic segmentation algorithm. Partial correlation test and multiple regression analysis were used to determine the effect of DFD on thicknesses of intraretinal layers. RESULTS: Disk-fovea distance correlated negatively with the overall average thickness in all the intraretinal layers (r ≤ -0.17, all P ≤ 0.025) except the ganglion cell layer and photoreceptor. In multiple regression analysis, greater DFD was associated with thinner nerve fiber layer (6.78 µm decrease per each millimeter increase in DFD, P < 0.001), thinner ganglion cell-inner plexiform layer (2.16 µm decrease per each millimeter increase in DFD, P = 0.039), thinner ganglion cell complex (8.94 µm decrease per each millimeter increase in DFD, P < 0.001), thinner central macular thickness (18.16 µm decrease per each millimeter increase in DFD, P < 0.001), and thinner total macular thickness (15.94 µm decrease per each millimeter increase in DFD, P < 0.001). CONCLUSION: Thinner measurements of macular intraretinal layers were significantly associated with greater DFD. A clinical assessment of macular intraretinal layers in the evaluation of various macular diseases should always be interpreted in the context of DFD.

A Flexible and Highly Sensitive Inductive Pressure Sensor Array Based on Ferrite Films.

There is a rapid growing demand for highly sensitive, easy adaptive and low-cost pressure sensing solutions in the fields of health monitoring, wearable electronics and home care. Here, we report a novel flexible inductive pressure sensor array with ultrahigh sensitivity and a simple construction, for large-area contact pressure measurements. In general, the device consists of three layers: a planar spiral inductor layer and ferrite film units attached on a polyethylene terephthalate (PET) membrane, which are separated by an array of elastic pillars. Importantly, by introducing the ferrite film with an excellent magnetic permeability, the effective permeability around the inductor is greatly influenced by the separation distance between the inductor and the ferrite film. As a result, the value of the inductance changes largely as the separation distance varies as an external load applies. Our device has achieved an ultrahigh sensitivity of 1.60 kPa-1 with a resolution of 13.61 Pa in the pressure range of 0-0.18 kPa, which is comparable to the current state-of-the-art flexible pressure sensors. More remarkably, our device shows an outstanding stability when exposed to environmental interferences, e.g., electrical noises from skin surfaces (within 0.08% variations) and a constant pressure load for more than 32 h (within 0.3% variations). In addition, the device exhibits a fast response time of 111 ms and a good repeatability under cyclic pressures varying from 38.45 to 177.82 Pa. To demonstrate its practical usage, we have successfully developed a 4 × 4 inductive pressure sensor array into a wearable keyboard for a smart electronic calendar application.

OIPAV: an Integrated Software System for Ophthalmic Image Processing, Analysis, and Visualization.

Ophthalmic medical images, such as optical coherence tomography (OCT) images and color photo of fundus, provide valuable information for clinical diagnosis and treatment of ophthalmic diseases. In this paper, we introduce a software system specially oriented to ophthalmic images processing, analysis, and visualization (OIPAV) to assist users. OIPAV is a cross-platform system built on a set of powerful and widely used toolkit libraries. Based on the plugin mechanism, the system has an extensible framework. It provides rich functionalities including data I/O, image processing, interaction, ophthalmic diseases detection, data analysis, and visualization. By using OIPAV, users can easily access to the ophthalmic image data manufactured from different imaging devices, facilitate workflows of processing ophthalmic images, and improve quantitative evaluations. With a satisfying function scalability and expandability, the software is applicable for both ophthalmic researchers and clinicians.

Elimination of Osteosarcoma by Necroptosis with Graphene Oxide-Associated Anti-HER2 Antibodies.

The prognosis for non-resectable or recurrent osteosarcoma (OS) remains poor. The finding that the majority of OS overexpress the protooncogene HER2 raises the possibility of using HER2 as a therapeutic target. However, clinical trials on the anti-HER2 antibody trastuzumab (TRA) in treating OS find no therapeutic benefit. HER2 overexpression in OS is not generally associated with gene amplification, with low-level expression regarded as HER2 "negative", as per criteria used to classify breast cancer HER2 status. Nevertheless, active HER2-targeting approaches, such as virus-based HER2 vaccines or CAR-T cells have generated promising results. More recently, it has been found that the noncovalent association of TRA with nanomaterial graphene oxide (GO) generates stable TRA/GO complexes capable of rapidly killing OS cells. TRA/GO induces oxidative stress and strong HER2 signaling to elicit immediate degradation of both cIAP (cellular inhibitor of apoptosis protein) and caspase 8, leading to activation of necroptosis. This is an attractive mechanism of cancer cell death as chemo/apoptosis-resistant tumors may remain susceptible to necroptosis. In addition, necroptosis is potentially immunogenic to promote tumor immunity, as opposed to apoptosis that tends to silence tumor immunity. Currently, no established anticancer therapeutics are known to eliminate cancers by necroptosis. The aim of this article is to review the rationale and mechanisms of TRA/GO-mediated cytotoxicity.

[Cloning and expression analysis of LncRNA-RgAGT2 responding to consecutive monoculture in Rehmannia glutinosa].

The consecutive monoculture obstacle is a major problem in the field of Rehmannia glutinosa( R. glutinosa),has severely declined the yield and quality of R. glutinosa. Here,using hi TAIL-PCR and RACE techniques,we have cloned the full-length transcript( 1 573 bp) of Unigene 29334＿All screened by DGE as a consecutive monoculture obstacle response gene of R. glutinosa. Based on ORF Finder prediction,all ORFs detected in the full-length transcript were less than 300 nt,which suggested that the above transcript was confirmed to be a long non-coding RNA( LncRNA). With alignment in R. glutinosa transcriptome,this LncRNA was partially homologous to alanine glyoxylate transaminase 2 gene( Rg AGT2),which was named LncRNA-RgATG2. To further explore the function of LncRNA-RgAGT2,we have examined expression patterns of LncRNA-RgAGT2 and Rg AGT2 at five critical development stages( seedling,elongation,pre-expanding,mid-expanding,late-expanding) in the first and second year replanting of R. glutinosa,respectively. The results indicated that LncRNA-RgAGT2,as a potential regulator,is possible to play a vital role in Rg AGT2 expression regulation. Meanwhile,LncRNA-RgAGT2 has presented significant variation in all development stages of R. glutinosa,which could be used as a " diagnostic label" to assess consecutive monoculture obstacle. This study,for the first time,showed that LncRNA was responsible for the response and regulation of consecutive monoculture obstacle,which would be a powerful supplement to reveal the molecular mechanisms of consecutive monoculture obstacle of R. glutinosa.

Improved fruit α-tocopherol, carotenoid, squalene and phytosterol contents through manipulation of Brassica juncea 3-HYDROXY-3-METHYLGLUTARYL-COA SYNTHASE1 in transgenic tomato.

3-Hydroxy-3-methylglutaryl-coenzyme A synthase (HMGS) in the mevalonate (MVA) pathway generates isoprenoids including phytosterols. Dietary phytosterols are important because they can lower blood cholesterol levels. Previously, the overexpression of Brassica juncea wild-type (wt) and mutant (S359A) BjHMGS1 in Arabidopsis up-regulated several genes in sterol biosynthesis and increased sterol content. Recombinant S359A had earlier displayed a 10-fold higher in vitro enzyme activity. Furthermore, tobacco HMGS overexpressors (OEs) exhibited improved sterol content, plant growth and seed yield. Increased growth and seed yield in tobacco OE-S359A over OE-wtBjHMGS1 coincided with elevations in NtSQS expression and sterol content. Herein, the overexpression of wt and mutant (S359A) BjHMGS1 in a crop plant, tomato (Solanum lycopersicum), caused an accumulation of MVA-derived squalene and phytosterols, as well as methylerythritol phosphate (MEP)-derived α-tocopherol (vitamin E) and carotenoids, which are important to human health as antioxidants. In tomato HMGS-OE seedlings, genes associated with the biosyntheses of C10, C15 and C20 universal precursors of isoprenoids, phytosterols, brassinosteroids, dolichols, methylerythritol phosphate, carotenoid and vitamin E were up-regulated. In OE-S359A tomato fruits, increased squalene and phytosterol contents over OE-wtBjHMGS1 were attributed to heightened SlHMGR2, SlFPS1, SlSQS and SlCYP710A11 expression. In both tomato OE-wtBjHMGS1 and OE-S359A fruits, the up-regulation of SlGPS and SlGGPPS1 in the MEP pathway that led to α-tocopherol and carotenoid accumulation indicated cross-talk between the MVA and MEP pathways. Taken together, the manipulation of BjHMGS1 represents a promising strategy to simultaneously elevate health-promoting squalene, phytosterols, α-tocopherol and carotenoids in tomato, an edible fruit.

Automated contour analysis of multi-cellular spheroids spreading through high content imaging.

The morphology of 2D cell colonies has been studied to understand tumor metastasis in the past decades. However, 2D cell cultures are lacking many features of 3D tissues, and their physiological behaviors are quite different from solid tumors in vivo. In this work, we studied the multi-cellular tumor spheroid (MCTS) spreading on the substrate, which keeps parts of 3D tissue characteristics and facilitates cell tracking through 2D imaging. By using a high content imaging system (HCS), we tracked multiple spheroids in one single 96-well plate for 36 h. An automated algorithm based on Otsu's method was developed to investigate the morphological details of spheroids through the quantification of radius length and its coefficients of variation. Spheroid spreading is altered by the PIP-platin, which was a novel platinum based drug previously reported by us with an inhibitory effect on cell migration. All parameters showed dose dependent decreases when PIP-platin concentration increased, indicating the inhibition of spheroid expansion by this compound. To investigate the surface roughness of spheroids affected by the drug, we applied the Fourier parameter ß and the normalized standard deviation of the radius STD r / [Formula: see text], which were found inversely proportional to the concentrations of PIP-platin. Particularly at the low drug concentrations, the indices of contour roughness appeared to be more sensitive than spheroid sizes, which could be the potential morphological markers for high content screening of drugs.

Curcumin prevents strokes in stroke-prone spontaneously hypertensive rats by improving vascular endothelial function.

BACKGROUND: Antioxidants have shown great promise in stroke prevention. Diarylheptanoids (also known as diphenylheptanoids) are a small class of plant secondary metabolites that possess antioxidant activity greater than that of α-tocopherol. Curcumin is the best known member and is mainly extracted from turmeric. This study aimed to explore whether curcumin has a preventive effect on stroke. METHODS: Stroke-prone spontaneously hypertensive rats (SHRsp) were randomly divided into control group (n = 10) and curcumin group (n = 10), and saline or curcumin (100 mg/kg/day) was administrated daily. Vascular endothelial function was examined by the relaxation of the artery in response to acetylcholine (ACH). The levels of reactive oxygen species (ROS) and nitric oxide (NO) were measured by using dihydroethidium (DHE) and 4, 5-diaminofluorescein (DAF-2 DA), respectively. The expression of uncoupling protein 2 (UCP2) was examined by RT-PCR and immunoblotting. RESULTS: Administration of curcumin significantly delayed the onset of stroke and increased the survival of SHRsp, which was ascribed to decreased ROS and improved endothelial dependent relaxation of carotid arteries. In the presence of UCP2 inhibitor genipin, both curcumin-mediated decrease of ROS and increase of NO production were blocked. CONCLUSION: Our study suggests that curcumin exerts a stroke preventive effect by attenuating oxidative stress to improve vascular endothelial function, which might be associated with UCP2 signaling.

Association of anti-HER2 antibody with graphene oxide for curative treatment of osteosarcoma.

The finding of HER2 overexpression in osteosarcoma (OS) makes HER2 a potential therapeutic target. However, studies indicate OS cells are nonresponsive to anti-HER2 antibody trastuzumab (TRA) therapy. We established stable, non-covalent association of TRA with nanomaterial graphene oxide (GO) to generated multivalent TRA/GO complexes that demonstrated markedly enhanced HER2-binding activity and capacity to rapidly kill OS cells. TRA/GO simultaneously induced oxidative stress and HER2 signaling in the target cells, leading to rapid depletion of the cellular inhibitors of apoptosis protein (cIAP) and caspase-8, formation of RIP1/RIPK3/MLKL necroptosome and necroptosis of the OS cells. Intravenous administration of TRA/GO eradicated established xenograft the OS in immunodeficient mice, resulting in indefinite survival of the animals, whereas TRA in its original form failed to do so. No appreciable side effects were observed with TRA/GO therapy. The results demonstrate a novel, nontoxic, curative therapy for a HER2pos cancer in a preclinical animal model.

Differential proteomic analysis of replanted Rehmannia glutinosa roots by iTRAQ reveals molecular mechanisms for formation of replant disease.

BACKGROUND: The normal growth of Rehmannia glutinosa, a widely used medicinal plant in China, is severely disturbed by replant disease. The formation of replant disease commonly involves interactions among plants, allelochemicals and microbes; however, these relationships remain largely unclear. As a result, no effective measures are currently available to treat replant disease. RESULTS: In this study, an integrated R. glutinosa transcriptome was constructed, from which an R. glutinosa protein library was obtained. iTRAQ technology was then used to investigate changes in the proteins in replanted R. glutinosa roots, and the proteins that were expressed in response to replant disease were identified. An integrated R. glutinosa transcriptome from different developmental stages of replanted and normal-growth R. glutinosa produced 65,659 transcripts, which were accurately translated into 47,818 proteins. Using this resource, a set of 189 proteins was found to be significantly differentially expressed between normal-growth and replanted R. glutinosa. Of the proteins that were significantly upregulated in replanted R. glutinosa, most were related to metabolism, immune responses, ROS generation, programmed cell death, ER stress, and lignin synthesis. CONCLUSIONS: By integrating these key events and the results of previous studies on replant disease formation, a new picture of the damaging mechanisms that cause replant disease stress emerged. Replant disease altered the metabolic balance of R. glutinosa, activated immune defence systems, increased levels of ROS and antioxidant enzymes, and initiated the processes of cell death and senescence in replanted R. glutinosa. Additionally, lignin deposition in R. glutinosa roots that was caused by replanting significantly inhibited tuberous root formation. These key processes provide important insights into the underlying mechanisms leading to the formation of replant disease and also for the subsequent development of new control measures to improve production and quality of replanted plants.

Transcriptome analysis reveals metabolic alteration due to consecutive monoculture and abiotic stress stimuli in Rehamannia glutinosa Libosch.

KEY MESSAGE: We deeply investigated the mechanism underlying metabolic regulation in response to consecutive monoculture (replanting disease) and different abiotic stresses that unfolded the response mechanism to consecutive monoculture problem through RNA-seq analysis. The consecutive monoculture problem (CMP) resulted of complex environmental stresses mediated by multiple factors. Previous studies have noted that multiple stress factors in consecutive monoculture soils or plants severely limited the interpretation of the critical molecular mechanism, and made a predict that the specifically responding factor was autotoxic allelochemicals. To identify the specifically responding genes, we compared transcriptome changes in roots of Rehamannia glutinosa Libosch using consecutive monoculture, salt, drought, and ferulic acid as stress factors. Comparing with normal growth, 2502, 2672, 2485, and 1956 genes were differentially expressed in R. glutinosa under consecutive monoculture practice, salt, drought, and ferulic acid stress, respectively. In addition, 510 genes were specifically expressed under consecutive monoculture, which were not present under the other stress conditions. Integrating the biological and enrichment analyses of the differentially expressed genes, the result demonstrated that the plants could alter enzyme genes expression to reconstruct the complicated metabolic pathways, which used to tolerate the CMP and abiotic stresses. Furthermore, most of the affected pathway genes were closely related to secondary metabolic processes, and the influence of consecutive monoculture practice on the transcriptome genes expression profile was very similar to the profile under salt stress and then to the profile under drought stress. The outlined schematic diagram unfolded the putative signal regulation mechanism in response to the CMP. Genes that differentially up- or down-regulated under consecutive monoculture practice may play important roles in the CMP or replanting disease in R. glutinosa.

[Advances on molecular mechanisms of Rehmannia glutinosa consecutive monoculture problem formation in multi-omics era].

Although consecutive monoculture problems have been studied for many years, no effective treatments are currently available. The complexity of systems triggered the formation of consecutive monoculture problems was one major cause. This paper elaborated the physiological and ecological mechanisms of consecutive monoculture problem formation based on the interaction relationship among multiple factors presented in the rhizosphere soil of consecutive monoculture plants. At same time, in this paper the multiple interactions among cultivated medicinal plants, autotoxic allelochemicals and rhizosphere microbial were proposed to be most important causes that derived the formation of consecutive monoculture problem. The paper also highlighted the advantage of 'omics' technologies integrating plant functional genomics and metabolomics as well as microbial macro-omics in understanding the multiple factor interaction under a particular ecological environment. Additionally, taking R. glutinosa as an example, the paper reviewed the molecular mechanism for the formation of R. glutinosa consecutive monoculture problem from the perspective of the accumulation of allelopathic autotoxins, the rhizosphere microecology catastrophe and theresponding of consecutive monoculture plants. Simultaneously, the roles of mutilple 'omics' technologies in comprehending these formation mechanism were described in detail. This paper provides finally a new insight to solve systematically the mechanism of consecutive monoculture problem formation on molecular level.

[Research progress of relationship between continuous cropping obstacles and microRNAs in Rehmannia glutinosa].

The efficacy of Rehmannia glutinosa which as a large quantity of traditional Chinese medicine is significant. However, the land must be given up after one season of R. glutinosa cultivation or replanted after a period of 8-10 years because of the severe continuous cropping obstacles. MicroRNAs is a class of endogenous non-coding small RNAs, which participate in regulation of physiological activities by target mRNA cleavage or translational repression in plants. In recent years,studies on the role of miRNAs in plants have made significant progresses,especially in medicinal plants．MiRNAs from some different medicinal plant species have been identified with regulatory effects．When plants are exposed to environmental stress, miRNAs act on stress-related genes and initiate stress-resistance mechanisms in the body against adverse factors. R. glutinosa is also a kind of environmental stress. It is conducive to deciphering the molecular mechanism of continuous cropping obstacles for us by researching miRNAs. This article reviews the production of miRNAs, mechanism, research approaches and characteristics of resisting the environmental stresses in plants, the development trends and future prospect of R. glutinosa miRNAs research.

CORRELATION OF OPTICAL INTENSITY ON OPTICAL COHERENCE TOMOGRAPHY AND VISUAL OUTCOME IN CENTRAL RETINAL ARTERY OCCLUSION.

PURPOSE: To investigate the relationship between optical coherence tomography (OCT) characteristics at baseline and visual outcome in central retinal artery occlusion (CRAO). METHODS: The medical charts and OCT images of patients with central retinal artery occlusion with follow-up for more than 90 days were reviewed. Optical intensities of inner retinal layers, outer nuclear layers, and photoreceptor/retinal pigment epithelium were measured using Image J software. Optical intensity ratio was calculated as the optical intensity of inner retinal layers divided by that of photoreceptor/retinal pigment epithelium. Retinal thickness over the nine early treatment diabetic retinopathy study regions was automatically calculated by OCT software. The relationship between best-corrected visual acuity at the last follow-up and OCT characteristics were analyzed using Spearman correlation. RESULTS: Fifteen eyes of 15 central retinal artery occlusion patients were included, with mean follow-up of 327.1 ± 184.1 days. The final best-corrected visual acuity was mildly or moderately correlated with retinal thicknesses, and strongly correlated with the optical intensity of photoreceptor/retinal pigment epithelium (r = -0.707, P = 0.003) and optical intensity ratio (r = 0.825, P < 0.001). CONCLUSION: Optical intensity ratio on OCT is highly correlated with visual prognosis in central retinal artery occlusion. It may be a potential biomarker of retinal ischemia.