Kinase CPK10 regulates low light-induced tomato flower drop downstream of IDL6 in a calcium-dependent manner.

Flower drop is a major cause for yield loss in many crops. Previously, we found that tomato (Solanum lycopersicum) INFLORESCENCE DEFICIENT IN ABSCISSION-Like (SlIDL6) contributes to flower drop induced by low light. However, the molecular mechanisms by which SlIDL6 acts as a signal to regulate low light-induced abscission remain unclear. In this study, SlIDL6 was found to elevate cytosolic Ca2+ concentrations ([Ca2+]cyt) in the abscission zone (AZ), which was required for SlIDL6-induced flower drop under low light. We further identified that one calcium-dependent protein kinase gene (SlCPK10) was highly expressed in the AZ and up-regulated by SlIDL6-triggered [Ca2+]cyt. Over-expression and knockout of SlCPK10 in tomato resulted in accelerated and delayed abscission, respectively. Genetic evidence further indicated that knockout of SlCPK10 significantly impaired the function of SlIDL6 in accelerating abscission. Furthermore, Ser-371 phosphorylation in SlCPK10 dependent on SlIDL6 was necessary and sufficient for its function in regulating flower drop, probably by stabilizing the SlCPK10 proteins. Taken together, our findings reveal that SlCPK10, as a downstream component of the IDL6 signaling pathway, regulates flower drop in tomato under low light stress.

A SlCLV3-SlWUS module regulates auxin and ethylene homeostasis in low light-induced tomato flower abscission.

Premature abscission of flowers and fruits triggered by low light stress can severely reduce crop yields. However, the underlying molecular mechanism of this organ abscission is not fully understood. Here, we show that a gene (SlCLV3) encoding CLAVATA3 (CLV3), a peptide hormone that regulates stem cell fate in meristems, is highly expressed in the pedicel abscission zone (AZ) in response to low light in tomato (Solanum lycopersicum). SlCLV3 knockdown and knockout lines exhibit delayed low light-induced flower drop. The receptor kinases SlCLV1 and BARELY ANY MERISTEM1 function in the SlCLV3 peptide-induced low light response in the AZ to decrease expression of the transcription factor gene WUSCHEL (SlWUS). DNA affinity purification sequencing identified the transcription factor genes KNOX-LIKE HOMEDOMAIN PROTEIN1 (SlKD1) and FRUITFULL2 (SlFUL2) as SlWUS target genes. Our data reveal that low light reduces SlWUS expression, resulting in higher SlKD1 and SlFUL2 expression in the AZ, thereby perturbing the auxin response gradient and causing increased ethylene production, eventually leading to the initiation of abscission. These results demonstrate that the SlCLV3-SlWUS signaling pathway plays a central role in low light-induced abscission by affecting auxin and ethylene homeostasis.

A simple clinical risk score (ABCDMP) for predicting mortality in patients with AECOPD and cardiovascular diseases.

BACKGROUND: The morbidity and mortality among hospital inpatients with AECOPD and CVDs remains unacceptably high. Currently, no risk score for predicting mortality has been specifically developed in patients with AECOPD and CVDs. We therefore aimed to derive and validate a simple clinical risk score to assess individuals' risk of poor prognosis. STUDY DESIGN AND METHODS: We evaluated inpatients with AECOPD and CVDs in a prospective, noninterventional, multicenter cohort study. We used multivariable logistic regression analysis to identify the independent prognostic risk factors and created a risk score model according to patients' data from a derivation cohort. Discrimination was evaluated by the area under the receiver-operating characteristic curve (AUC), and calibration was assessed by the Hosmer-Lemeshow goodness-of-fit test. The model was validated and compared with the BAP-65, CURB-65, DECAF and NIVO models in a validation cohort. RESULTS: We derived a combined risk score, the ABCDMP score, that included the following variables: age > 75 years, BUN > 7 mmol/L, consolidation, diastolic blood pressure ≤ 60 mmHg, mental status altered, and pulse > 109 beats/min. Discrimination (AUC 0.847, 95% CI, 0.805-0.890) and calibration (Hosmer‒Lemeshow statistic, P = 0.142) were good in the derivation cohort and similar in the validation cohort (AUC 0.811, 95% CI, 0.755-0.868). The ABCDMP score had significantly better predictivity for in-hospital mortality than the BAP-65, CURB-65, DECAF, and NIVO scores (all P < 0.001). Additionally, the new score also had moderate predictive performance for 3-year mortality and can be used to stratify patients into different management groups. CONCLUSIONS: The ABCDMP risk score could help predict mortality in AECOPD and CVDs patients and guide further clinical research on risk-based treatment. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trail Registry NO.:ChiCTR2100044625; URL: http://www.chictr.org.cn/showproj.aspx?proj=121626 .

Characteristics, treatments, in-hospital and long-term outcomes among inpatients with acute exacerbation of chronic obstructive pulmonary disease in China: sex differences in a large cohort study.

BACKGROUND: Data related to the characteristics, treatments and clinical outcomes of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients in China are limited, and sex differences are still a neglected topic. METHODS: The patients hospitalized for AECOPD were prospectively enrolled from ten medical centers in China between September 2017 and July 2021. Patients from some centers received follow-up for 3 years. Data regarding the characteristics, treatments and in-hospital and long-term clinical outcomes from male and female AECOPD patients included in the cohort were analyzed and compared. RESULTS: In total, 14,007 patients with AECOPD were included in the study, and 11,020 (78.7%) were males. Compared with males, female patients were older (74.02 ± 10.79 vs. 71.86 ± 10.23 years, P < 0.001), and had more comorbidities (2.22 ± 1.64 vs. 1.73 ± 1.56, P < 0.001), a higher frequency of altered mental status (5.0% vs. 2.9%, P < 0.001), lower diastolic blood pressure (78.04 ± 12.96 vs. 79.04 ± 12.47 mmHg, P < 0.001). In addition, there were also significant sex differences in a range of laboratory and radiographic findings. Females were more likely to receive antibiotics, high levels of respiratory support and ICU admission than males. The in-hospital and 3-year mortality were not significantly different between males and females (1.4% vs. 1.5%, P = 0.711; 35.3% vs. 31.4%, P = 0.058), while female smokers with AECOPD had higher in-hospital mortality than male smokers (3.3% vs. 1.2%, P = 0.002) and male smokers exhibited a trend toward higher 3-year mortality compared to female smokers (40.7% vs. 33.1%, P = 0.146). CONCLUSIONS: In AECOPD inpatients, females and males had similar in-hospital and long-term survival despite some sex differences in clinical characteristics and treatments, but female smokers had significantly worse in-hospital outcomes than male smokers. CLINICAL TRIAL REGISTRATION: Retrospectively registered, registration number is ChiCTR2100044625, date of registration 21/03/2021. URL: http://www.chictr.org.cn/showproj.aspx?proj=121626 .

SlBEL11 regulates flavonoid biosynthesis, thus fine-tuning auxin efflux to prevent premature fruit drop in tomato.

Auxin regulates flower and fruit abscission, but how developmental signals mediate auxin transport in abscission remains unclear. Here, we reveal the role of the transcription factor BEL1-LIKE HOMEODOMAIN11 (SlBEL11) in regulating auxin transport during abscission in tomato (Solanum lycopersicum). SlBEL11 is highly expressed in the fruit abscission zone, and its expression increases during fruit development. Knockdown of SlBEL11 expression by RNA interference (RNAi) caused premature fruit drop at the breaker (Br) and 3 d post-breaker (Br+3) stages of fruit development. Transcriptome and metabolome analysis of SlBEL11-RNAi lines revealed impaired flavonoid biosynthesis and decreased levels of most flavonoids, especially quercetin, which functions as an auxin transport inhibitor. This suggested that SlBEL11 prevents premature fruit abscission by modulating auxin efflux from fruits, which is crucial for the formation of an auxin response gradient. Indeed, quercetin treatment suppressed premature fruit drop in SlBEL11-RNAi plants. DNA affinity purification sequencing (DAP-seq) analysis indicated that SlBEL11 induced expression of the transcription factor gene SlMYB111 by directly binding to its promoter. Chromatin immunoprecipitation-quantitative polymerase chain reaction and electrophoretic mobility shift assay showed that S. lycopersicum MYELOBLASTOSIS VIRAL ONCOGENE HOMOLOG111 (SlMYB111) induces the expression of the core flavonoid biosynthesis genes SlCHS1, SlCHI, SlF3H, and SlFLS by directly binding to their promoters. Our findings suggest that the SlBEL11-SlMYB111 module modulates flavonoid biosynthesis to fine-tune auxin efflux from fruits and thus maintain an auxin response gradient in the pedicel, thereby preventing premature fruit drop.

Risk factors of in-hospital mortality and discriminating capacity of NIVO score in exacerbations of COPD requiring noninvasive ventilation.

BACKGROUND: Noninvasive mechanical ventilation (NIV) is recommended as the initial mode of ventilation to treat acute respiratory failure in patients with AECOPD. The Noninvasive Ventilation Outcomes (NIVO) score has been proposed to evaluate the prognosis in patients with AECOPD requiring assisted NIV. However, it is not validated in Chinese patients. METHODS: We used data from the MAGNET AECOPD Registry study, which is a prospective, noninterventional, multicenter, real-world study conducted between September 2017 and July 2021 in China. Data for the potential risk factors of mortality were collected and the NIVO score was calculated, and the in-hospital mortality was evaluated using the NIVO risk score. RESULTS: A total of 1164 patients were included in the study, and 57 patients (4.9%) died during their hospital stay. Multiple logistic regression analysis revealed that age ≥75 years, DBP <60 mmHg, Glasgow Coma Scale ≤14, anemia and BUN >7 mmol/L were independent predictors of in-hospital mortality. The in-hospital mortality was associated with an increase in the risk level of NIVO score and the difference was statistically significant (p < .001). The NIVO risk score showed an acceptable accuracy for predicting the in-hospital mortality in AECOPD requiring assisted NIV (AUC: 0.657, 95% CI: 0.584-0.729, p < .001). CONCLUSION: Our findings identified predictors of mortality in patients with AECOPD receiving NIV, providing useful information to identify severe patients and guide the management of AECOPD. The NIVO score showed an acceptable predictive value for AECOPD receiving NIV in Chinese patients, and additional studies are needed to develop and validate predictive scores based on specific populations.

The HD-Zip transcription factor SlHB15A regulates abscission by modulating jasmonoyl-isoleucine biosynthesis.

Plant organ abscission, a process that is important for development and reproductive success, is inhibited by the phytohormone auxin and promoted by another phytohormone, jasmonic acid (JA). However, the molecular mechanisms underlying the antagonistic effects of auxin and JA in organ abscission are unknown. We identified a tomato (Solanum lycopersicum) class III homeodomain-leucine zipper transcription factor, HOMEOBOX15A (SlHB15A), which was highly expressed in the flower pedicel abscission zone and induced by auxin. Knocking out SlHB15A using clustered regularly interspaced short palindromic repeats-associated protein 9 technology significantly accelerated abscission. In contrast, overexpression of microRNA166-resistant SlHB15A (mSlHB15A) delayed abscission. RNA sequencing and reverse transcription-quantitative PCR analyses showed that knocking out SlHB15A altered the expression of genes related to JA biosynthesis and signaling. Furthermore, functional analysis indicated that SlHB15A regulates abscission by depressing JA-isoleucine (JA-Ile) levels through inhabiting the expression of JASMONATE-RESISTANT1 (SlJAR1), a gene involved in JA-Ile biosynthesis, which could induce abscission-dependent and abscission-independent ethylene signaling. SlHB15A bound directly to the SlJAR1 promoter to silence SlJAR1, thus delaying abscission. We also found that flower removal enhanced JA-Ile content and that application of JA-Ile severely impaired the inhibitory effects of auxin on abscission. These results indicated that SlHB15A mediates the antagonistic effect of auxin and JA-Ile during tomato pedicel abscission, while auxin inhibits abscission through the SlHB15A-SlJAR1 module.

Inflorescence abscission protein SlIDL6 promotes low light intensity-induced tomato flower abscission.

In many fruiting plant species, flower abscission is induced by low light stress. Here, we elucidated how signaling mediated by the peptide INFLORESCENCE DEFICIENT IN ABSCISSION (IDA) controls low light-induced flower drop in tomato (Solanum lycopersicum). We analyzed the expression patterns of an IDA-Like gene (SlIDL6) during low light-induced flower abscission, and used tandem mass spectrometry to identify and characterize the mature SlIDL6 peptide. Tomato knockout lines were created to investigate the in vivo function of SlIDL6. In addition, yeast one-hybrid assays were used to investigate the binding of the SlWRKY17 transcription factor to the SlIDL6 promoter, and silencing of SlWRKY17 expression delayed low light-induced flower abscission. SlIDL6 was specifically expressed in the abscission zone and at high levels during low light-induced abscission and ethylene treatment. SlIDL6 knockout lines showed delayed low light-induced flower drop, and the application of SlIDL6 peptide accelerated abscission. Overexpression of SlIDL6 rescued the ida mutant phenotype in Arabidopsis (Arabidopsis thaliana), suggesting functional conservation between species. SlIDL6-mediated abscission was via an ethylene-independent pathway. We report a SlWRKY17-SlIDL6 regulatory module that functions in low light promoted abscission by increasing the expression of enzymes involved in cell wall remodeling and disassembly.

SlERF52 regulates SlTIP1;1 expression to accelerate tomato pedicel abscission.

Abscission of plant organs is induced by developmental signals and diverse environmental stimuli and involves multiple regulatory networks, including biotic or abiotic stress-impaired auxin flux in the abscission zone (AZ). Depletion of auxin activates AZ ethylene (ETH) production and triggers acceleration of abscission, a process that requires hydrogen peroxide (H2O2). However, the interaction between these networks and the underlying mechanisms that control abscission are poorly understood. Here, we found that expression of tonoplast intrinsic proteins, which belong to the aquaporin (AQP) family in the AZ was important for tomato (Solanum lycopersicum) pedicel abscission. Liquid chromatography-tandem mass spectrometry and in situ hybridization revealed that SlTIP1;1 was most abundant and specifically present in the tomato pedicel AZ. SlTIP1;1 localized in the plasma membrane and tonoplast. Knockout of SlTIP1;1 resulted in delayed abscission, whereas overexpression of SlTIP1;1 accelerated abscission. Further analysis indicated that SlTIP1;1 mediated abscission via gating of cytoplasmic H2O2 concentrations and osmotic water permeability (Pf). Elevated cytoplasmic levels of H2O2 caused a suppressed auxin signal in the early abscission stage and enhanced ETH production during abscission. Furthermore, we found that increasing Pf was required to enhance the turgor pressure to supply the break force for AZ cell separation. Moreover, we observed that SlERF52 bound directly to the SlTIP1;1 promoter to regulate its expression, demonstrating a positive loop in which cytoplasmic H2O2 activates ETH production, which activates SlERF52. This, in turn, induces SlTIP1;1, which leads to elevated cytoplasmic H2O2 and water influx.

Tomato SlIDA has a critical role in tomato fertilization by modifying reactive oxygen species homeostasis.

Anther development and pollen tube elongation are key steps for pollination and fertilization. The timing and spatial distribution of reactive oxygen species (ROS) and programmed cell death are central to these processes, but the regulatory mechanism of ROS production is not well understood. Inflorescence deficient in abscission (IDA) is implicated in many plant development and responses to environmental stimuli. However, their role in reproductive development is still unknown. We generated tomato knockout lines (CR-slida) of an IDA homolog (SlIDA), which is expressed in the tapetum, septum and pollen tube, and observed a severe defect in male gametes. Further analysis indicated that there was a programmed cell death defect in the tapetum and septum and a failure of anther dehiscence in the CR-slida lines, likely related to insufficient ROS signal. Liquid chromatography-tandem mass spectrometry identified mature SlIDA as a 14-mer EPIP peptide, which was shown to be secreted, and a complementation experiment showed that application of a synthetic 14-mer EPIP peptide rescued the CR-slida defect and enhanced the ROS signal. Moreover, the application of the ROS scavengers diphenyleneiodonium or Mn-TMPP suppressed peptide function. Collectively, our results revealed that SlIDA plays an essential role in pollen development and pollen tube elongation by modulating ROS homeostasis.

A zinc finger protein BBX19 interacts with ABF3 to affect drought tolerance negatively in chrysanthemum.

Drought is an environmental factor that can severely influence plant development and distribution, and greatly affect the yield and economic value of crops. We characterized CmBBX19, a BBX family subgroup IV member gene, from the transcriptome database of Chrysanthemum morifolium in response to drought stress. Drought stress and ABA treatments downregulated the expression of CmBBX19. We generated CmBBX19-overexpressing (CmBBX19-OX) lines and CmBBX19-suppressing lines (CmBBX19-RNAi), and found that suppressed expression of CmBBX19 led to enhanced drought tolerance compared with the wild-type (WT) controls, while CmBBX19-OX lines exhibited reduced drought tolerance. Downstream gene analysis showed that CmBBX19 modulates drought tolerance mainly through inducing changes in the expression of ABA-dependent pathway genes, including protective protein, redox balance and cell wall biogenesis genes, such as responsive to ABA 18, peroxidase 12, and cellulose synthase-like protein G2. Moreover, CmBBX19 was shown to interact with CmABF3, a master ABA signaling component, to suppress expression of these downstream genes. We conclude that BBX19-ABF3 module functions in the regulation of drought tolerance of chrysanthemum through an ABA-dependent pathway.

Long non-coding RNA CRNDE promotes cell apoptosis by suppressing miR-495 in inflammatory bowel disease.

OBJECTIVE: This article aims to investigate the mechanism of microRNA-495 (miR-495) and long non-coding RNA CRNDE on the apoptosis of colonic epithelial cells in inflammatory bowel diseases (IBDs). METHODS: The mouse model of IBD was induced by dextran sulfate sodium (DSS), and human colonic epithelial cell lines (HT-29, LOVO, and Caco-2) were treated with DSS, and received cell transfection. RNA interference was used to down-regulate CRNDE expression. RESULTS: CRNDE and SOCS1 were highly expressed, but miR-495 was lowly expressed in the DSS-induced colitis tissues and colonic epithelial cell lines. Interference of CRNDE inhibited cell apoptosis of DSS-induced colonic epithelial cells. The interaction between CRNDE and miR-495 was confirmed by RNA immunoprecipitation and RNA pull-down assay. The target relationship between miR-495 and SOCS1 was confirmed by the luciferase reporter assay. CRNDE promoted DSS-induced colonic epithelial cell apoptosis via miR-495/SOCS1. CRNDE interference in DSS-induced colitis mouse model alleviated clinical manifestations of IBD. CONCLUSIONS: Our findings demonstrated that CRNDE promoted DSS-induced colonic epithelial cell apoptosis via suppressing miR-495 and increasing SOCS1, indicating CRNDE as a novel target of treating IBD.

Discriminative pattern of reduced cerebral blood flow in Parkinson's disease and Parkinsonism-Plus syndrome: an ASL-MRI study.

BACKGROUND: Accurate identification of Parkinson's disease (PD) and Parkinsonism-Plus syndrome (PPS), especially in the early stage of the disease, is very important. The purpose of this study was to investigate the discriminative spatial pattern of cerebral blood flow (CBF) between patients with PD and PPS. METHODS: Arterial spin labeling (ASL) perfusion-weighted imaging was performed in 20 patients with PD (mean age 56.35 ± 7.56 years), 16 patients with PPS (mean age 59.62 ± 6.89 years), and 17 healthy controls (HCs, mean age 54.17 ± 6.58 years). Voxel-wise comparison of the CBF was performed among PD, PPS, and HC groups. The receiver operating characteristic (ROC) curve was used to evaluate the performance of CBF in discriminating between PD and PPS. The relationship between CBF and non-motor neuropsychological scores was assessed by correlation analysis. RESULTS: PD group showed a significantly decreased CBF in the right cerebelum_crus2, the left middle frontal gyrus (MFG), the triangle inferior frontal gyrus (IFG_Tri), the left frontal medial orbital gyrus (FG_Med_Orb) and the left caudate nucleus (CN) compared with the HC group (P < 0.05). Besides the above regions, the left supplementary motor area (SMA), the right thalamus had decreased CBF in the PPS group compared with the HC group (P < 0.05). PPS group had lower CBF value in the left MFG, the left IFG_Tri, the left CN, the left SMA, and the right thalamus compared with the PD group (P < 0.05). CBFs in left IFG_Tri, the left CN, the left SMA, and the right thalamus had moderate to high capacity in discriminating between PD and PPS patients (AUC 0.719-0.831). The CBF was positively correlated with the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores in PD patients, while positively correlated with the MMSE, Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD) scores in PPS patients (P < 0.05). CONCLUSION: PD and PPS patients have certain discriminative patterns of reduced CBFs, which can be used as a surrogate marker for differential diagnosis.

Berberrubine and its analog, hydroxypropyl-berberrubine, regulate LDLR and PCSK9 expression via the ERK signal pathway to exert cholesterol-lowering effects in human hepatoma HepG2 cells.

Berberine (BBR), the major isoquinoline alkaloid in Chinese herb Rhizoma coptidis, has significant lipid-lowering effect by upregulating hepatic low-density lipoprotein receptor (LDLR) expression. In a previous study, we have indicated that berberrubine (M3), a major metabolite of BBR in vivo, displays the most potential hypolipidemic effects via upregulating LDLR expression in human hepatoma (HepG2) cells compared with BBR and 3 other metabolites. Accordingly, 9 M3 analogs (A1-A9) were modified at the C9 position. We aimed to find a new promising agent by evaluating the cholesterol-lowering effect and clarifying the related molecular mechanism. In the current study, the cellular cholesterol content was assayed with a commercial cholesterol assay kit. Real-time polymerase chain reaction and Western blot assay were used to explore the molecular mechanism of M3 and its analogs on the hypolipidemic effect. Among M3 and its analogs, hydroxypropyl-berberrubine (A8) exhibited the highest potential effects on the upregulation of LDLR expression, which was accompanied by a steady decline of proprotein convertase subtilisin/kexin type 9 (PCSK9) messenger RNA and protein levels. Furthermore, inhibition of extracellular signal-regulated kinase (ERK) activity with PD98059 prevented the upregulation of LDLR and downregulation of PCSK9 induced by A8. The current study revealed that M3 and its structurally modified analog, A8, could regulate hepatic LDLR and PCSK9 expression to exert lipid-lowering effects via the ERK signal pathway, while A8 showed a stronger effect and might be a promising drug candidate against hyperlipidemia.

MicroRNA1917 targets CTR4 splice variants to regulate ethylene responses in tomato.

Ethylene perception is regulated by receptors, and the downstream protein CONSTITUTIVE TRIPLE RESPONSE1 is a key suppressor of ethylene signalling. The non-conserved tomato (Solanum lycopersicum) microRNA1917 (Sly-miR1917) mediates degradation of SlCTR4 splice variants (SlCTR4sv) but the molecular details of this pathway remain unknown. Sly-miR1917 and the targeted SlCTR4sv are ubiquitously expressed in all tomato organs. Overexpression of Sly-miR1917 enhances ethylene responses, including the triple response in etiolated seedlings, in the absence of ethylene, as well as epinastic petiole growth, accelerated pedicel abscission, and fruit ripening. Enhanced ethylene signalling in Sly-miR1917-overexpressing plants (1917-OE) is accompanied by up-regulation of ethylene biosynthesis and signalling genes, and increased ethylene emission. These phenotypes were recovered by repressing the positive ethylene regulator EIN2. Moreover, the Sly-miR1917-targeted SlCTR4 splice variant SlCTR4sv3, expressed specifically in the abscission zone, exhibited the opposite expression pattern to Sly-miR1917. Complementation of the Arabidopsis thaliana ctr-1 mutant and yeast two-hybrid and bimolecular fluorescence complementation assays suggested that SlCTR4sv3 functions in ethylene signalling. Co-expression of Sly-miR1917 and SlCTR4sv3 in Nicotiana benthamiana further suggested that Sly-miR1917 cleaves SlCTR4sv3 in vivo. Database homology searching revealed a Solanum tuberosum CTR-like splice variant containing a Sly-miR1917 binding sequence, and a homologue of mature Sly-miR1917 in potato, indicating a conserved function for miR1917 and the regulatory miRNA-mediated ethylene network in solanaceous species.

LncRNA TUG1 promoted viability and associated with gemcitabine resistant in pancreatic ductal adenocarcinoma.

OBJECTIVE: To investigate the underlying mechanism of lncRNA TUG1 in pancreatic ductal adenocarcinoma (PDAC). METHODS: The expression of TUG1 was defined by qRT-PCR. The apoptotic cells were detected by flow cytometry assay. The cell migration and invasion were measured by scratch assay and Transwell assay. The level of ERK pathway was detected using Western blot. RESULTS: Compared with normal tissues and cells, the expression of TUG1 was up-regulated in pancreatic cancer tissue and cells. Meanwhile, knockdown of TUG1 could promote PDAC cells apoptosis and inhibit PDAC cells viability, migration and invasion. In addition, overexpression of TUG1 enhanced the gemcitabine chemoresistance of PDAC cells. Surprisingly, gemcitabine combined with SCH772984 (a suppressor of ERK pathway) could reverse the drug resistance resulted from overexpression of TUG1. CONCLUSION: TUG1 promoted the viability of PDAC cells and enhanced its resistance of gemcitabine.

A Zinc Finger Protein Regulates Flowering Time and Abiotic Stress Tolerance in Chrysanthemum by Modulating Gibberellin Biosynthesis.

Flowering time and an ability to tolerate abiotic stresses are important for plant growth and development. We characterized BBX24, a zinc finger transcription factor gene, from Chrysanthemum morifolium and found it to be associated with both flowering time and stress tolerance. Transgenic lines with suppressed expression of Cm-BBX24 (Cm-BBX24-RNAi) flowered earlier than wild-type plants and showed decreased tolerance to freezing and drought stresses. Global expression analysis revealed that genes associated with both photoperiod and gibberellin (GA) biosynthesis pathways were upregulated in Cm-BBX24-RNAi lines, relative to the wild type. By contrast, genes that were upregulated in overexpressing lines (Cm-BBX24-OX), but downregulated in Cm-BBX24-RNAi lines (both relative to the wild type), included genes related to compatible solutes and carbohydrate metabolism, both of which are associated with abiotic stress. Cm-BBX24 expression was also influenced by daylength and GA4/7 application. Under long days, changes in endogenous GA1, GA4, GA19, and GA20 levels occurred in young leaves of transgenic lines, relative to the wild type. Regulation of flowering involves the FLOWERING TIME gene, which integrates photoperiod and GA biosynthesis pathways. We postulate that Cm-BBX24 plays a dual role, modulating both flowering time and abiotic stress tolerance in chrysanthemum, at least in part by influencing GA biosynthesis.

Emerging techniques for assisting and accelerating food freezing processes: A review of recent research progresses.

Freezing plays an important role in food preservation and the emergence of rapid freezing technologies can be highly beneficial to the food industry. This paper reviews some novel food freezing technologies, including high-pressure freezing (HPF), ultrasound-assisted freezing (UAF), electrically disturbed freezing (EF) and magnetically disturbed freezing (MF), microwave-assisted freezing (MWF), and osmo-dehydro-freezing (ODF). HPF and UAF can initiate ice nucleation rapidly, leading to uniform distribution of ice crystals and the control of their size and shape. Specifically, the former is focused on increasing the degree of supercooling, whereas the latter aims to decrease it. Direct current electric freezing (DC-EF) and alternating current electric freezing (AC-EF) exhibit different effects on ice nucleation. DC-EF can promote ice nucleation and AC-EF has the opposite effect. Furthermore, ODF has been successfully used for freezing various vegetables and fruit. MWF cannot control the nucleation temperature, but can decrease supercooling degree, thus decreasing the size of ice crystals. The heat and mass transfer processes during ODF have been investigated experimentally and modeled mathematically. More studies should be carried out to understand the effects of these technologies on food freezing process.

MiR-3910 Promotes the Growth and Migration of Cancer Cells in the Progression of Hepatocellular Carcinoma.

INTRODUCTION: Previous studies have reported that specific depletion of mammalian sterile-like kinase (MST1) in the mouse liver driven Hepatocellular carcinoma (HCC). However, how the expression of MST1 was regulated in the progression of HCC remains largely unknown. MATERIALS AND METHODS: The expression of miR-3910 in the HCC tissues and cell lines were examined using q-PCR. The functions of miR-3910 in HCC were examined using MTT assay, Boyden chamber assay and soft agar assay. The effects of miR-3910 on the metastasis of HCC cells were evaluated using the mouse model. RESULTS: Here, we have shown that miR-3910 regulated the expression of MST1. MiR-3910 was up-regulated in HCC samples and cell lines, and the expression of miR-3910 was induced by the oncogenic RasV12. In the functional study, miR-3910 was found to promote the growth and migration of HCC cells, and knocking down miR-3910 inhibited the metastasis of HCC cells. Mechanically, it was found that miR-3910 activated YAP signaling by targeting MST1. CONCLUSION: Taken together, this study demonstrated that miR-3910 exerted oncogenic effects on the progression of HCC and suggested that miR-3910 might be a therapeutic target for cancer therapy.

[Tract-based spatial statistics analysis on the white matter of patients with temporal lobe epilepsy and automatic recognition].

This study aims to determine the salient brain regions with abnormal changes in white matter structures from diffusion tensor imaging (DTI) images of the patients with temporal lobe epilepsy (TLE), and to discriminate the patients with TLE from normal controls (NCs). Firstly, the DTI images from 50 subjects (28 NCs and 22 TLE) were acquired. Secondly, the four measures including the fractional anisotropy (FA), the mean diffusivity (MD), the axial diffusivity (AD) and the radial diffusivity (RD) were calculated. Thirdly, the tract-based spatial statistics (TBSS) was adopted to extract the measures in brain regions with significant differences between the two compared groups. Fourthly, the obtained measures were used as input features of the support vector machine (SVM) for classification, and the support vector machine-recursive feature elimination (SVM-RFE) was compared with the support vector machine-tract-based spatial statistics (SVM-TBSS) method. Finally, the essential brain regions and their spatial distribution were analyzed and discussed. The experimental results showed that the FA measures of the TLE group decreased significantly in the corpus callosum, superior longitudinal fasciculus, corona radiata, external capsule, internal capsule, inferior fronto-occipital fasciculus, fasciculus uncinatus and sagittal stratum, which were nearly bilaterally distributed, while the MD and RD increased significantly in most of these brain regions of the TLE group. Although the AD also increased, the differences were not statistically significant. The SVM-TBSS classifier obtained accuracies of 82%, 76% and 76% using the FA, MD and RD for classification, respectively, and 80% using combined measures. The SVM-RFE classifier obtained accuracies of 90%, 90% and 92% using the FA, MD and RD respectively, while the highest accuracy was 100% using combined measures. These results demonstrated that the SVM-RFE outperformed the SVM-TBSS, and the dominant characteristic influencing classification in brain regions were in associative and commissural fibers. These results illustrated that the measures of DTI images could reveal the abnormal changes in white matter structure of patients with TLE, providing effective information to clarify its pathological mechanism, localize the focus and diagnose automatically.