The CRY2-COP1-HY5-BBX7/8 module regulates blue light-dependent cold acclimation in Arabidopsis.

Light and temperature are two key environmental factors that coordinately regulate plant growth and development. Although the mechanisms that integrate signaling mediated by cold and red light have been unraveled, the roles of the blue light photoreceptors cryptochromes in plant responses to cold remain unclear. In this study, we demonstrate that the CRYPTOCHROME2 (CRY2)-COP1-HY5-BBX7/8 module regulates blue light-dependent cold acclimation in Arabidopsis thaliana. We show that phosphorylated forms of CRY2 induced by blue light are stabilized by cold stress and that cold-stabilized CRY2 competes with the transcription factor HY5 to attenuate the HY5-COP1 interaction, thereby allowing HY5 to accumulate at cold temperatures. Furthermore, our data demonstrate that B-BOX DOMAIN PROTEIN7 (BBX7) and BBX8 function as direct HY5 targets that positively regulate freezing tolerance by modulating the expression of a set of cold-responsive genes, which mainly occurs independently of the C-repeat-binding factor pathway. Our study uncovers a mechanistic framework by which CRY2-mediated blue-light signaling enhances freezing tolerance, shedding light on the molecular mechanisms underlying the crosstalk between cold and light signaling pathways in plants.

Coronatine Enhances Chilling Tolerance of Tomato Plants by Inducing Chilling-Related Epigenetic Adaptations and Transcriptional Reprogramming.

Low temperature is an important environmental factor limiting the widespread planting of tropical and subtropical crops. The application of plant regulator coronatine, which is an analog of Jasmonic acid (JA), is an effective approach to enhancing crop's resistance to chilling stress and other abiotic stresses. However, the function and mechanism of coronatine in promoting chilling resistance of tomato is unknown. In this study, coronatine treatment was demonstrated to significantly increase tomato chilling tolerance. Coronatine increases H3K4me3 modifications to make greater chromatin accessibility in multiple chilling-activated genes. Corresponding to that, the expression of CBFs, other chilling-responsive transcription factor (TF) genes, and JA-responsive genes is significantly induced by coronatine to trigger an extensive transcriptional reprogramming, thus resulting in a comprehensive chilling adaptation. These results indicate that coronatine enhances the chilling tolerance of tomato plants by inducing epigenetic adaptations and transcriptional reprogramming.

Body Mass Index May Positively Correlate with Bone Mineral Density of Lumbar Vertebra and Femoral Neck in Postmenopausal Females.

BACKGROUND: Our study aimed to explore the relationship between body mass index (BMI) and bone mineral density (BMD) of lumbar vertebra and femoral neck in postmenopausal females. MATERIAL/METHODS: From September 2012 to September 2014, 236 healthy postmenopausal females who underwent physical examinations at the Women & Children's Health Care Hospital of Linyi were enrolled into our study. These subjects were divided into 3 groups: underweight group, normal weight group, and overweight group. In addition, there were 2 age stratifications: <60 years old and ≥60 years old. DPX-L type dual-energy X-ray bone densitometry (American Lunar Company) was used to measure the BMD of lumbar vertebra and femoral neck in the recruited subjects. Pearson test was used for correlation analysis. RESULTS: BMDs and T-scores of lumbar vertebra (L1-L4), femoral neck, proximal femur, and Ward's triangle region among the groups were ranked as follows: underweight group < normal weight group < overweight group. There were significant differences in body weight and BMI among the underweight, normal weight, and overweight groups (P<0.05). The T-scores of all examined anatomic locations showed significant differences between the underweight group and normal weight group, as well as between the underweight group and overweight group (both P<0.05). Only the T-scores of lumbar vertebra L2-L4 had significant differences between the normal weight group and overweight group (P<0.05). The BMDs of all anatomic components under study showed statistical differences in both age stratifications between the overweight group and underweight group, as well as between the overweight group and normal weight group (both P<0.05). When stratified above 60 years old, the BMDs of lumbar vertebra (L1, L2 and L4) showed statistical differences between the normal weight group and underweight group (P<0.05). Various factors could be ranked according to the absolute values of correlation coefficients as below: body weight, BMI, height, and age. Body weight, BMI, and height were positively correlated with the BMDs of all examined anatomic locations (P<0.05). However, age was negatively correlated with the various components of the body (lumbar vertebra L1, L2 and L4, femoral neck, proximal femur, Ward's triangle region: P<0.05; lumbar vertebra L3: P>0.05). CONCLUSIONS: Our study provides evidence that body weight and BMI are important factors affecting BMD. Postmenopausal females with low BMI are more likely to have osteopenia, and are likely to develop osteoporosis. BMI can be used as an important index to prevent osteoporosis.

Analysis on spatial structure characteristics and influencing factors of Beijing-Tianjin-Hebei Region MICE cities.

Industrial upgrading and transfer is one of the three key areas in the coordinated development of Beijing-Tianjin-Hebei Region. Meetings, incentives, conferences and exhibitions (MICE) are important means of promoting industrial upgrading. Urban MICE industry, as an important carrier of event activities, become an important gripper for coordinated development of Beijing-Tianjin-Hebei Region. City exhibition space structure plays an dominant role in regional economic development, and it will greatly promote smooth implementation of the coordinated development strategy of Beijing-Tianjin-Hebei Region. In this paper, 13 prefecture-level cities in Beijing, Tianjin and Hebei were selected as research objects, and the data from 2012 to 2018 were selected to establish a gravity model of the attractiveness of MICE cities. With the help of UCINET software, the network density, centrality, cohesive subgroup and core-edge of nodes researches were obtained to analyze the spatial structure characteristics of the attractiveness of MICE cities in Beijing-Tianjin-Hebei Region. The influencing factors of the spatial characteristics of MICE city attractiveness are analyzed by using geographically weighted regression model. The results show that: (1) Beijing, as the overall core area, act as a prominent role. Beijing strengthens the attraction to the superior resources of the surrounding areas, but the network of MICE cities tends to be unbalanced. (2) Overall space forms a subgroup from a single independent subgroup to a subgroup that is spatially separated from each other and acts as an intermediary channel to connect each other, and the core region decreases from 3 to 2. Langfang was removed from the list, leaving Beijing and Tianjin as the core. (3) The influence of supporting facilities, urban environment and population factors on the MICE city attractiveness of Beijing-Tianjin-Hebei Region is increasing gradually. The influence of tourism development level on the MICE city attractiveness of Beijing-Tianjin-Hebei Region is decreasing gradually. The influence of economic development level and Internet development level on the MICE city attractiveness of Beijing-Tianjin-Hebei Region remains unchanged.

CPK28-NLP7 module integrates cold-induced Ca2+ signal and transcriptional reprogramming in Arabidopsis.

Exposure to cold triggers a spike in cytosolic calcium (Ca2+) that often leads to transcriptional reprogramming in plants. However, how this Ca2+ signal is perceived and relayed to the downstream cold signaling pathway remains unknown. Here, we show that the CALCIUM-DEPENDENT PROTEIN KINASE 28 (CPK28) initiates a phosphorylation cascade to specify transcriptional reprogramming downstream of cold-induced Ca2+ signal. Plasma membrane (PM)-localized CPK28 is activated rapidly upon cold shock within 10 seconds in a Ca2+-dependent manner. CPK28 then phosphorylates and promotes the nuclear translocation of NIN-LIKE PROTEIN 7 (NLP7), a transcription factor that specifies the transcriptional reprogramming of cold-responsive gene sets in response to Ca2+, thereby positively regulating plant response to cold stress. This study elucidates a previously unidentified mechanism by which the CPK28-NLP7 regulatory module integrates cold-evoked Ca2+ signal and transcriptome and thus uncovers a key strategy for the rapid perception and transduction of cold signals from the PM to the nucleus.

Natural polymorphism of ZmICE1 contributes to amino acid metabolism that impacts cold tolerance in maize.

Cold stress negatively affects maize (Zea mays L.) growth, development and yield. Metabolic adjustments contribute to the adaptation of maize under cold stress. We show here that the transcription factor INDUCER OF CBF EXPRESSION 1 (ZmICE1) plays a prominent role in reprogramming amino acid metabolome and COLD-RESPONSIVE (COR) genes during cold stress in maize. Derivatives of amino acids glutamate/asparagine (Glu/Asn) induce a burst of mitochondrial reactive oxygen species, which suppress the cold-mediated induction of DEHYDRATION RESPONSE ELEMENT-BINDING PROTEIN 1 (ZmDREB1) genes and impair cold tolerance. ZmICE1 blocks this negative regulation of cold tolerance by directly repressing the expression of the key Glu/Asn biosynthesis genes, ASPARAGINE SYNTHETASEs. Moreover, ZmICE1 directly regulates the expression of DREB1s. Natural variation at the ZmICE1 promoter determines the binding affinity of the transcriptional activator ZmMYB39, a positive regulator of cold tolerance in maize, resulting in different degrees of ZmICE1 transcription and cold tolerance across inbred lines. This study thus unravels a mechanism of cold tolerance in maize and provides potential targets for engineering cold-tolerant varieties.

Effect of revascularization on IL-6 and TNF-α in patients with thromboangiitis obliterans.

The aim of the study was to investigate the effects of revascularization in treating patients with thromboangiitis obliterans (TAO), to analyze the prognosis of TAO. The treatment group comprised 32 patients with TAO of lower limbs who were selected between March 2012 and March 2017. Patients in the treatment group were treated with revascularization (vascular bypass surgery, catheter-directed thrombolysis and angioplasty, endovascular angioplasty + stening, thromboectomy and/or endarterectomy) + Western medicine. Another 33 patients with TAO who were treated with Western medicine alone comprised the control group. Treatment outcomes were compared between the groups. Serum levels of interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor-α (TNF-α) were also detected and compared between the groups. Multivariate analysis was performed to identify the factors related to prognosis. Compared with control group, treatment outcomes were significantly better in the treatment group (P<0.05). After treatment, the serum levels of IL-6, IL-8 and TNF-α significantly decreased in both groups, and the decrease in the treatment group was more significant (P<0.01). Multivariate analysis revealed that vascular bypass surgery and preoperative ischemic degree are associated with treatment effect. Our results show that revascularization treatment of TAO is conducive to clinical symptoms and dysfunction of inflammatory cytokines, and the type of surgery and surgical timing significantly affect treatment outcomes.

MicroRNA-409-3p inhibits osteosarcoma cell migration and invasion by targeting catenin-δ1.

Osteosarcoma is the most common primary bone cancer which is associated with early metastatic potential and poor prognosis. However, the molecular mechanisms underlying osteosarcoma progression are not well characterized. Here, we investigated the role of miR-409-3p in osteosarcoma metastasis. Osteosarcoma tissue showed decreased expression of miR-409-3p compared to adjacent non-tumorous tissue. The expression level of miR-409-3p was negatively correlated with osteosarcoma metastasis. Overexpression of miR-409-3p in osteosarcoma cells (U2OS) inhibited cell migration and invasion. Bioinformatics analysis showed that catenin-δ1 (CTNND1, p120-catenin) is a direct target of miR-409-3p. Overexpression of miR-409-3p repressed the expression of catenin-δ1 in U2OS cells at both mRNA and protein levels. Meanwhile, miR-409-3p repressed the activity of luciferase reporter containing the 3'-untranslated region (3'UTR) of CTNND1 gene. Furthermore, expression of catenin-δ1 rescued the inhibitory effect of miR-409-3p on cell migration and invasion. Altogether, these results indicated that miR-409-3p targets catenin-δ1 to repress osteosarcoma metastasis.

Let-7c miRNA Inhibits the Proliferation and Migration of Heat-Denatured Dermal Fibroblasts Through Down-Regulating HSP70.

Wound healing is a complex physiological process necessitating the coordinated action of various cell types, signals and microRNAs (miRNAs). However, little is known regarding the role of miRNAs in mediating this process. In the present study, we show that let-7c miRNA is decreased in heat-denatured fibroblasts and that inhibiting let-7c expression leads to the increased proliferation and migration of dermal fibroblasts, whereas the overexpression of let-7c exerts an opposite effect. Further investigation has identified heat shock protein 70 as a direct target of let-7c and has demonstrated that the expression of HSP70 in fibroblasts is negatively correlated with let-7c levels. Moreover, down-regulation of let-7c expression is accompanied by up-regulation of Bcl-2 expression and down-regulation of Bax expression, both of which are the downstream genes of HSP70. Notably, the knockdown of HSP70 by HSP70 siRNA apparently abrogates the stimulatory effect of let-7c inhibitor on heat-denatured fibroblasts proliferation and migration. Overall, we have identified let-7c as a key regulator that inhibits fibroblasts proliferation and migration during wound healing.

Repetitive magnetic stimulation affects the microenvironment of nerve regeneration and evoked potentials after spinal cord injury.

Repetitive magnetic stimulation has been shown to alter local blood flow of the brain, excite the corticospinal tract and muscle, and induce motor function recovery. We established a rat model of acute spinal cord injury using the modified Allen's method. After 4 hours of injury, rat models received repetitive magnetic stimulation, with a stimulus intensity of 35% maximum output intensity, 5-Hz frequency, 5 seconds for each sequence, and an interval of 2 minutes. This was repeated for a total of 10 sequences, once a day, 5 days in a week, for 2 consecutive weeks. After repetitive magnetic stimulation, the number of apoptotic cells decreased, matrix metalloproteinase 9/2 gene and protein expression decreased, nestin expression increased, somatosensory and motor-evoked potentials recovered, and motor function recovered in the injured spinal cord. These findings confirm that repetitive magnetic stimulation of the spinal cord improved the microenvironment of neural regeneration, reduced neuronal apoptosis, and induced neuroprotective and repair effects on the injured spinal cord.

The Cotransplantation of Olfactory Ensheathing Cells with Bone Marrow Mesenchymal Stem Cells Exerts Antiapoptotic Effects in Adult Rats after Spinal Cord Injury.

The mechanisms behind the repairing effects of the cotransplantation of olfactory ensheathing cells (OECs) with bone marrow mesenchymal stromal cells (BMSCs) have not been fully understood. Therefore, we investigated the effects of the cotransplantation of OECs with BMSCs on antiapoptotic effects in adult rats for which the models of SCI are induced. We examined the changes in body weight, histopathological changes, apoptosis, and the expressions of apoptosis-related proteins after 14 days and 28 days after transplantation. We also assessed animal locomotion using BBB test. We found that treatment with OECs and BMSCs had a remissive effect on behavioral outcome and histopathological changes induced SCI. Furthermore, we observed the significant antiapoptotic effect on cotransplant treated group. In addition, cotransplantation of OECs with BMSCs was found to have more significant repairing effect than that of OECs or BMSCs alone. Furthermore, the recovery of hind limb could be related to antiapoptotic effect of OECs and BMSCs through downregulating the apoptotic pathways. Finally, our data suggested the cotransplantation of OECs with BMSCs holds promise for a potential cure after SCI through the ability to incorporate into the spinal cord.

[Treatment of tibial fracture with interlocking intramedullary nail and tripus].

OBJECTIVE: To explore the method and effect of inter-locking intramedullary nail and tripus in closed reduction for treating tibial fracture. METHODS: One hundred and twenty-six patients of tibial fractures were treated by inter-locking intramedullary nail and tripus in closed reduction. There were 76 males and 50 females aged from 25 to 68, the mean age was 38; There were 86 close fractures and 40 open fractures (Gustilo I and II type). AO classification system was used for all cases, fracture type A in 49 cases, type B in 41 cases, type C in 36 cases. RESULTS: All patients were followed up for 10 to 16 months. Fratures were cured, according to the criteria of Johner-Wruhs, the results were excellent in 103 cases, good in 18 cases, fair in 5 cases. CONCLUSION: Inter-locking intramedullary nail is the optimal operation method in treating tibial fracture. Static locking should be a routine way, and closed reduction, no stripping periosteum, infectious rate and complications are reduced. Through tripus work intensity are reduced and reduction easily during operation.