Prevention and Potential Treatment Strategies for Respiratory Syncytial Virus.

Respiratory syncytial virus (RSV) is a significant viral pathogen that causes respiratory infections in infants, the elderly, and immunocompromised individuals. RSV-related illnesses impose a substantial economic burden worldwide annually. The molecular structure, function, and in vivo interaction mechanisms of RSV have received more comprehensive attention in recent times, and significant progress has been made in developing inhibitors targeting various stages of the RSV replication cycle. These include fusion inhibitors, RSV polymerase inhibitors, and nucleoprotein inhibitors, as well as FDA-approved RSV prophylactic drugs palivizumab and nirsevimab. The research community is hopeful that these developments might provide easier access to knowledge and might spark new ideas for research programs.

[Updated reproductive toxicology of polybrominated diphenyl ether].

Since 1970, polybrominated diphenyl ether (PBDE) has been widely used as additive flame retardants in everyday consumer products, including polyurethane foam and electronic products like mattresses and upholstered furniture. Thermoplastics, mixed in polymers, do not chemically bond with plastics, textiles, etc., and therefore can be separated from the product into the environment. Because of its high lipophilicity, accumulation, degradation-resistance and biochemical toxicity, PBDE can invade the human body in a variety of ways and is toxic to multiple systems in the human body. PBDE affects the male reproductive system in many aspects, as by causing sperm quality decline, epididymis, seminal vesicle and prostate dysplasia, sperm head deformity, and decreased levels of testosterone and other reproductive hormones. PBDE also affects male reproductive function from the genetic aspect, as by altering the sperm DNA methylation level, inducing sperm chromatin damage, etc. Some environmental factors, such as high-fat diet and indoor dust increase, can indirectly promote the reproductive toxicity of PBDE. This article reviews the impacts of PBDE on exposed populations and the animal reproductive system and the latest research progress at home and abroad.

Enantioselective Total Synthesis of (-)-Pavidolide B.

The enantioselective synthesis of (-)-pavidolide B (1) was achieved in a linear sequence of 10 steps. The key steps are (a) an enantioselective organocatalytic cyclopropanation; (b) a radical-based cascade annulation for the regio- and diastereo-selective synthesis of the highly functionalized lactone 3 bearing the characteristic tricyclic core and seven contiguous stereocenters;

Longitudinal Changes in Liver Aminotransferases Predict Metabolic Syndrome in Chinese Patients with Nonviral Hepatitis.

OBJECTIVE: This study explored the correlation of longitudinal changes in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels with the incidence of metabolic syndrome (Mets) based on a dynamic health examination cohort. METHODS: A Mets-free dynamic cohort involving 4541 participants who underwent at least three health examinations from 2006 to 2011 was included in the study. Mets was defined according to the Chinese Medical Association Diabetes Branch definition that included hypertension, obesity, hyperlipidemia, and hyperglycemia. Generalized estimating equation (GEE) model was used to analyze multivariate relative risk (RR) of repeated observations of ALT and AST in quartiles for Mets or its components according to gender. RESULTS: In all, 826 Mets cases were reported. Adjustment of relevant parameters indicated that time-varying changes in ALT and AST levels were positively associated with the incidence of Mets in a dose-response manner. Positive association between high ALT levels and fatty liver was much stronger than that between high AST levels and fatty liver, particularly in male participants. These associations were consistently observed in the following subgroups: participants with ALT and AST levels of <40 U/L, participants with of <25 kg/m2, and participants with non-fatty liver. Furthermore, participants with 2 Mets components at baseline showed lower multivariate adjusted RRs of ALT and AST for Mets than participants with 0-1 Mets component. CONCLUSION: These results suggested that elevated serum ALT and AST levels were early biomarkers of Mets or its components.

Regulation of pepc gene expression in Anabaena sp. PCC 7120 and its effects on cyclic electron flow around photosystem I and tolerances to environmental stresses.

Since pepc gene encoding phosphoenolpyruvate carboxylase (PEPCase) has been cloned from Anabaena sp. PCC 7120 and other cyanobacteria, the effects of pepc gene expression on photosynthesis have not been reported yet. In this study, we constructed mutants containing either upregulated (forward) or downregulated (reverse) pepc gene in Anabaena sp. PCC 7120. Results from real-time quantitative polymerase chain reaction (RT-qPCR), Western blot and enzymatic analysis showed that PEPCase activity was significantly reduced in the reverse mutant compared with the wild type, and that of the forward mutant was obviously increased. Interestingly, the net photosynthesis in both the reverse mutant and the forward mutant were higher than that of the wild type, but dark respiration was decreased only in the reverse mutant. The absorbance changes of P700 upon saturation pulse showed the photosystem I (PSI) activity was inhibited, as reflected by Y(I), and Y(NA) was elevated, and dark reduction of P700(+) was stimulated, indicating enhanced cyclic electron flow (CEF) around PSI in the reverse mutant. Additionally, the reverse mutant photosynthesis was higher than that of the wild type in low temperature, low and high pH, and high salinity, and this implies increased tolerance in the reverse mutant through downregulated pepc gene.

Imprinting analysis of porcine DIO3 gene in two fetal stages and association analysis with carcass and meat quality traits.

Imprinted genes play important roles in mammalian growth, development and behavior. In this study, we obtained 1568 bp mRNA sequence of porcine DIO3 (deiodinase, iodothyronine, type III), and also identified its imprinting status during porcine fetal development. The complete open reading frame (ORF) encoding 278 amino acids. The porcine DIO3 mRNA was expressed predominantly in backfat, mildly in liver, uterus, kidney, heart, small intestine, muscle and stomach, and almost absent in spleen and lung. A single nucleotide polymorphism in exon (A/C (687)) was used to investigate the allele frequencies in different pig breeds and the imprinting status in porcine embryonic tissues. The results indicate that DIO3 was imprinted in all the tested tissues. Statistical analysis showed the DIO3 gene polymorphism was significantly associated with almost all the fat deposition and carcass traits, including lean meat percentage (LMP), fat meat percentage (FMP), ratio of lean to fat (RLF), shoulder fat thickness (SFT), sixth-seventh rib fat thickness (RFT), buttock fat thickness (BFT), loin eye area (LEA), and intramuscular fat (IMF).

[The effects of different herbal compound and extracts from different extraction methods on hypoxia tolerance in mice].

Objective: To investigate the effects of different prescription compositions of traditional Chinese medicine and its different extraction methods of compound formula extracts on hypoxia tolerance in mice, in order to preferably select their prescription compositions and preparation extraction methods. Methods: Male BALB/c mice were randomly divided into 6 groups: blank control group, compound danshen group, compound Rhodiola Rosea alcohol-water extract group (Rhodiola rosea, Astragali Radix, Polygonati Rhizoma, Lycii Fructus), compound Rhodiola Rosea water extract group, compound Astragalus alcohol-water extract group (Astragali Radix, Polygonati Rhizoma, Lycii Fructus) and compound Astragalus water extract group, 30 mice in each group. Each group was administered continuously by gavage for 10 d. The blank group was gavaged with sterilized injection water. The mice in the other groups were treated with 0.15 g/kg of compound danshen, 3 g/kg of compound Rhodiola Rosea alcohol-water extract or water extract, and 1.7 g/kg of compound Astragalus alcohol-water extract or water extract, respectively. Each group was subjected to normobaric hypoxia tolerance test, sodium nitrite toxicity survival test and acute cerebral ischemia-hypoxia test 1 h after the last gavage, and the mice brain tissues were used to determine the activity of antioxidant enzymes and metabolites related to oxidative stress. Results: Compared with the blank control group, in normobaric hypoxia tolerance test, the survival time of mice in the compound danshen group and the compound Astragalus alcohol-water extract group and water extraction group was prolonged significantly (P＜0.01), and the number of open-mouth gasping after cerebral ischemia and hypoxia was increased significantly (P＜0.05). There was no statistical difference in survival time after sodium nitrite injection in each group. Compared with the blank control group, the activities of T-AOC, SOD, GSH and CAT were increased significantly (P＜0.05, P＜0.01) and the content of MDA was decreased significantly (P＜0.01) in the compound Astragalus water extract group. Compared with the compound danshen group, the activities of SOD, CAT and GSH were increased significantly (P＜0.01, P＜0.05) and the content of MDA was decreased significantly (P＜0.05). Conclusion: Compound Astragalus water extraction has the best effect of hypoxia tolerance, compound Rhodiola Rosea can eliminate Rhodiola rosea and consists of Astragali Radix, Polygonati Rhizoma, Lycii Fructus and its extraction method is water extraction.

[The changes of Dectin-1 and TLR2 in human umbilical vein endothelial cells stimulated by Aspergillus fumigatus].

OBJECTIVE: To observe the changes of TLR-2, Dectin-1 expression on endothelial cells, and to explore their role in the immune response after contact with Aspergillus fumigatus. METHODS: Aspergillus fumigatus and human umbilical vein endothelial cells were co-incubated. Cells were collected respectively after incubation for 0 h, 1 h, 2 h, 4 h and 6 h. TLR2 and Dectin-1 receptor expressions were detected by flow cytometry, and their protein was measured by Western blot. The distribution of the receptors in the cells were observed by immunofluorescence. RESULT: TLR2 and Dectin-1 were expressed on the endothelial cell surface in quiescent condition. The mean fluorescence intensity of TLR2 on endothelial cells decreased from 45 to 13 stimulation by Aspergillus fumigatus, but the mean fluorescence intensity of Dectin-1 increased from 13 to 35 in the first 2 hours and then decreased. By Western blot, the electrophoresis strip of Dectin-1 was most bright in 2 hours after contact with the fungus, and then decreased 4 and 6 hours. TLR2 did not change significantly. Dectin-1 with fluorescent labeling was seen in spores and hyphae as well as in the cell membrane under confocal microscope. TLR2 was detected only on cell surface. CONCLUSION: TLR2 and Dectin-1 were expressed by endothelial cells, and may be useful in the identification of Aspergillus fumigatus.

Identification of Circular RNA Expression Profiles in White Adipocytes and Their Roles in Adipogenesis.

Obesity and its related metabolic diseases have become great public health threats worldwide. Although accumulated evidence suggests that circRNA is a new type of non-coding RNAs regulating various physiological and pathological processes, little attention has been paid to the expression profiles and functions of circRNAs in white adipose tissue. In this study, 3,771 circRNAs were detected in three stages of white adipogenesis (preadipocyte, differentiating preadipocyte, and mature adipocyte) by RNA-seq. Experimental validation suggested that the RNA-seq results are highly reliable. We found that nearly 10% of genes which expressed linear RNAs in adipocytes could also generate circRNAs. In addition, 40% of them produced multiple circRNA isoforms. We performed correlation analysis and found that a great deal of circRNAs (nearly 50%) and their parental genes were highly correlated in expression levels. A total of 41 differential expression circRNAs (DECs) were detected during adipogenesis and an extremely high ratio of them (80%) were correlated with their parental genes, indicating these circRNAs may potentially play roles in regulating the expression of their parental genes. KEGG enrichment and GO annotation of the parental genes suggesting that the DECs may participate in several adipogenesis-related pathways. Following rigorous selection, we found that many up-regulated circRNAs contain multiple miRNAs binding sites, such as miR17, miR-30c, and miR-130, indicating they may potentially facilitate their regulatory functions by acting as miRNA sponges. These results suggest that plenty of circRNAs are expressed in white adipogenesis and the DECs may serve as new candidates for future adipogenesis regulation.

[N-cadherin as a receptor for adhesion and endocytosis of Aspergillus fumigatus by human umbilical vein endothelial cells].

OBJECTIVE: To study the receptor for adhesion and endocytosis of Aspergillus fumigatus hyphae by human umbilical vein endothelial cells (HUVEC). METHODS: Aspergillus fumigatus hyphae were incubated with the total protein of HUVEC for investigating the binding of N-cadherin and the fungus. After the model of adhesion and endocytosis of Aspergillus fumigatus by HUVEC was established, the capacity of adhesion and endocytosis was evaluated with the presence of the antibody to N-cadherin. RESULTS: N-cadherin sticked to the surface of Aspergillus fumigatus. Adhesion and endocytosis were inhibited with the presence of the antibody to N-cadherin. CONCLUSION: N-cadherin is a receptor for adhesion and endocytosis of Aspergillus fumigatus by HUVEC.

[Clinical Features of Nosocomial Infections in Agranulocytosis Patients with Hematological Malignancies and Analysis of Risk Factors].

OBJECTIVE: To explore the clinical features and risk factors for nosocomial infections in agranulocytosis patients with hematological malignancies so as to provide basis for clinical prevention and treatment of nosocomial infections. METHODS: The clinical data of 725 patients with agranulocytosis in the First Hospital of Lanzhou University from May 2015 to May 2018 were retrospectively analyzed, including sex, age, primary disease, treatment stage, agranulocytosis degree, agranulocytosis duration, nosocomial infection, infectous site, average length of stay and average days of infection. Univariate analysis (Chi-square test) and multivariate analysis (non-conditional Logistic regression models) were used to analyze the risk factors of nosocomial infection. RESULTS: The most common sites of nosocomial infection in agranulocytosis patients with hematological maliguancies were upper respiratory tract, accounting for 24.0%, followed by lung (16.2%) and blood stream (13.8%). In disease composition, acute leukemia holded the first place, accounting for 82.1%, among which the acute myeloid leukemia had the highest infection rate, accounting for 73.3%, followed by acute lymphoblastic leukemia. The infection rates were 68.0% and 66.7% for multiple myeloma, 79.3% and 84.5% for acute leukemia at the initial induction and relapse stages, respectively. 184 pathogenic bacteria were isolated clinically, of which 126 were a Gram-negative bacteria, 23 were Gram-positive bacteria and 35 were fungi, accounting for 68.48%, 12.50% and 19.02%, respectively. It was found that age, primary disease, degree and duration of granulocyte deficiency, chemotherapy, glucocorticoid use and disease status all associated with nosocomial infection (P＜0.05). Multivariate unconditional logistic regression analysis showed that acute leukemia, absolute count of neutrophils＜0.2×109/L, chemotherapy and disease unremitting were the main risk factors of nosocomial infection. CONCLUSION: The patients with malignant hematological agranulocytosis are a high-risk population of nosocomial infection. Nosocomial infection rate is still high, especially in patients with acute leukemia who have received chemotherapy or without complete remission or neutrophil absolute count less than 0.2×109/L. Thus early intervention measures should be taken to reduce the incidence of nosocomial infection and mortality.

[Distribution and Drug Sensitivity of Pathogens Causing Nosocomial Infection in Patients with Hematological Granulocytosis].

OBJECTIVE: To investigate the distribution and drug resistance of nosocomial infection pathogens in AL patients with hematological agranulocytosis, so as to provide evidence for the clinical rational use of antibiotics. METHODS: Pathogenic data of 504 hospitalized patients with agranulocytosis caused by nosocomial infection in the Department of Hematology, the First Hospital of Lanzhou University from May 2015 to May 2018 were collected and retrospectively analyzed for the distribution of pathogenic bacteria and the results of drug susceptibility. RESULTS: The isolated pathogenic bacteria strains amounted to 184, out of which, 168 strains (91.3%) orginated from the patients with acute leukemia, while 16 strains (8.7%) originated from the patients with non-acute leukemia. The positive samples mainly originated from blood stream, the isolated bacteria from which were 81 straims (44%); then originated from sputam and pharynx swabs, from which isolated bacteria amounted to 54 strains (29.3%) and 35 strains (19%) respectively. In the pathogenic bacteria, the Gram-negative bacteria amounted to 126 strains accounting for 68.46%, out of which the most commond bacteria strains were Klebseilla pneumoniae, cscherichia coli and Pseudomonas aeruginosa; the Gram positive bocteria amounted to 23 strains accounting for 12.5%, mainly staphy lococeus anreus, and Staphylococcus epitermidis; the fungi amounted to 35 strains accounting for 19.02%, mainly Candida albicans. The detection rates of Escherichia coli and Klebsiella pneumoniae producing extended-spectrum ß-lactamases (ESBLs) were 40.0% and 22.2%, respectively. They were 100% sensitive to amikacin and 27.8% resistant to carbapenems. Klebsiella pneumoniae had the highest sensitivity to amikacin, 94.44% to ampicillin, 97.22% to carbapenems and 100% sensitive to ammonia. Their penicillin-resistance rate was the highest, up to 80%; Pseudomonas aeruginosa was sensitive to the antibiotics (＞80%）. Methicillin-resistant Staphylococcus aureus and methicillin-resistant coagulase-negative Staphylococcus were detected in Gram-positive bacteria. The susceptibility rate of main Gram-positive bacteria to vancomycin and linezolid was 100%, and they were 100% resistant to penicillin. CONCLUSION: Gram-negative bacteria are the main pathogens of nosocomial infection in patients with hematological agranulocytosis. Pathogens have different resistance to antimicrobial agents. It is important to know the distribution and susceptibility of common pathogens for rational selection of antimicrobial agents and control of nosocomial infection.

Using HJ-CCD image and PLS algorithm to estimate the yield of field-grown winter wheat.

Remote sensing has been used as an important means of estimating crop production, especially for the estimation of crop yield in the middle and late growth period. In order to further improve the accuracy of estimating winter wheat yield through remote sensing, this study analyzed the quantitative relationship between satellite remote sensing variables obtained from HJ-CCD images and the winter wheat yield, and used the partial least square (PLS) algorithm to construct and validate the multivariate remote sensing models of estimating the yield. The research showed a close relationship between yield and most remote sensing variables. Significant multiple correlations were also recorded between most remote sensing variables. The optimal principal components numbers of PLS models used to estimate yield were 4. Green normalized difference vegetation index (GNDVI), optimized soil-adjusted vegetation index (OSAVI), normalized difference vegetation index (NDVI) and plant senescence reflectance index (PSRI) were sensitive variables for yield remote sensing estimation. Through model development and model validation evaluation, the yield estimation model's coefficients of determination (R2) were 0.81 and 0.74 respectively. The root mean square error (RMSE) were 693.9 kg ha-1 and 786.5 kg ha-1. It showed that the PLS algorithm model estimates the yield better than the linear regression (LR) and principal components analysis (PCA) algorithms. The estimation accuracy was improved by more than 20% than the LR algorithm, and was 13% higher than the PCA algorithm. The results could provide an effective way to improve the estimation accuracy of winter wheat yield by remote sensing, and was conducive to large-area application and promotion.

NADPH Oxidases: The Vital Performers and Center Hubs during Plant Growth and Signaling.

NADPH oxidases (NOXs), mostly known as respiratory burst oxidase homologs (RBOHs), are the key producers of reactive oxygen species (ROS) in plants. A lot of literature has addressed ROS signaling in plant development regulation and stress responses as well as on the enzyme's structure, evolution, function, regulation and associated mechanisms, manifesting the role of NOXs/RBOHs as the vital performers and center hubs during plant growth and signaling. This review focuses on recent advances of NOXs/RBOHs on cell growth, hormone interaction, calcium signaling, abiotic stress responses, and immunity. Several primary particles, including Ca2+, CDPKs, BIK1, ROPs/RACs, CERK, FER, ANX, SnRK and SIK1-mediated regulatory mechanisms, are fully summarized to illustrate the signaling behavior of NOXs/RBOHs and their sophisticated and dexterous crosstalks. Diverse expression and activation regulation models endow NOXs/RBOHs powerful and versatile functions in plants to maintain innate immune homeostasis and development integrity. NOXs/RBOHs and their related regulatory items are the ideal targets for crop improvement in both yield and quality during agricultural practices.

Quantitative monitoring of leaf area index in wheat of different plant types by integrating NDVI and Beer-Lambert law.

Normalized difference vegetation index (NDVI) is one of the most important vegetation indices in crop remote sensing. It features a simple, fast, and non-destructive method and has been widely used in remote monitoring of crop growing status. Beer-Lambert law is widely used in calculating crop leaf area index (LAI), however, it is time-consuming detection and low in output. Our objective was to improve the accuracy of monitoring LAI through remote sensing by integrating NDVI and Beer-Lambert law. In this study, the Beer-Lambert law was firstly modified to construct a monitoring model with NDVI as the independent variable. Secondly, experimental data of wheat from different years and various plant types (erectophile, planophile and middle types) was used to validate the modified model. The results showed that at 130 DAS (days after sowing), the differences in NDVI, leaf area index (LAI) and extinction coefficient (k) of the three plant types with significantly different leaf orientation values (LOVs) reached the maximum. The NDVI of the planophile-type wheat reached saturation earlier than that of the middle and erectophile types. The undetermined parameters of the model (LAI = -ln (a1 × NDVI + b1)/(a2 × NDVI + b2)) were related to the plant type of wheat. For the erectophile-type cultivars (LOV ≥ 60°), the parameters for the modified model were, a1 = 0.306, a2 = -0.534, b1 = -0.065, and b2 = 0.541. For the middle-type cultivars (30° < LOV < 60°), the parameters were, a1 = 0.392, a2 = -0.881, b1 = 0.028, and b2 = 0.845. And for the planophile-type cultivars (LOV ≤ 30°), those parameters were, a1 = 0.596, a2 = -1.306, b1 = 0.014, and b2 = 1.130. Verification proved that the modified model based on integrating NDVI and Beer-Lambert law was better than Beer-Lambert law model only or NDVI-LAI direct model only. It was feasible to quantitatively monitor the LAI of different plant-type wheat by integrating NDVI and Beer-Lambert law, especially for erectophile-type wheat (R2 = 0.905, RMSE = 0.36, RE = 0.10). The monitoring model proposed in this study can accurately reflect the dynamic changes of plant canopy structure parameters, and provides a novel method for determining plant LAI.

Interaction between TaNOX7 and TaCDPK13 Contributes to Plant Fertility and Drought Tolerance by Regulating ROS Production.

Reactive oxygen species (ROS) homeostasis is critical for both physiological processes and stress responses of plants. NADPH oxidases (NOXs) are the key producers of ROS in plants. However, their functions in ROS homeostasis and plant growth regulation in wheat (Triticum aestivum) are little investigated. Here, we cloned and characterized a NOX isoform TaNOX7 in wheat. Overexpression of TaNOX7 in rice led to enhanced root length, ROS production, drought tolerance as well as bigger panicles and higher yield but shorter growth period duration. Further results indicate that TaCDPK13, a member of calcium-dependent protein kinases (CDPKs), can directly interact with TaNOX7 and enhance ROS production in plants. These results demonstrate that TaNOX7 plays crucial roles in wheat development, fertility, and drought tolerance via interaction with TaCDPK13, which may act as an upstream regulator of TaNOX7 to regulate ROS production in wheat.

Assemblies of copper bis(triazole) coordination polymers using the same keggin polyoxometalate template.

Four inorganic-organic hybrid compounds, [Cu(I)(4)(bte)(4)(SiW(12)O(40))] (1), [Cu(II)(2)(bte)(4)(SiW(12)O(40))].4H(2)O (2) [bte = 1,2-bis(1,2,4-triazol-1-yl)ethane], [Cu(I)(4)(btb)(2)(SiW(12)O(40))].2H(2)O (3), and [Cu(II)(2)(btb)(4)(SiW(12)O(40))].2H(2)O (4) [btb = 1,4-bis(1,2,4-triazol-1-yl)butane], were hydrothermally synthesized through use of the same Keggin polyoxometalate as the template and tuning the molar ratio of the bis(triazole) ligand to the Cu(II) ion. The ratio of the bis(triazole) ligand to Cu(II) has a crucial influence on the structures of this series. Single-crystal X-ray diffraction analyses indicate that compound 1 is constructed by tetranuclear ring-connecting chains and polymerized [Cu(bte)](+) chains, between which SiW(12) anions are inserted to form a three-dimensional (3D) structure. Compound 2 shows a (4(4).6(2)) two-dimensional grid sheet. The discrete SiW(12) anions are sandwiched by the sheets, just like "hamburgers". Compound 3 presents channel-like [Cu(2)(btb)](2+) polymerized chains, which are further connected by SiW(12) anions to construct a 3D framework. Compound 4 exhibits a (6(6)) 3D Cu-btb framework with hexagonal channels, into which the tetradentate SiW(12) anions are incorporated. The thermal stabilities of the compounds are discussed.

[Values of Different Prognostical Score Systems in Evaluation of Clinical Efficacy for Patients with Newly Diagnosed Chronic Myeloid Leukemia].

OBJECTIVE: To explore the values of 4 prognostic score systems in evaluation of clinical effecacy for patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) treated with imatnib mesylate (IM) and the relationship between 4 prognostic score systems and deep molecular response (MR4.5). METHODS: The clinical data of 240 CML-CP patients treated with imatinib mesylate in our hospital between Janunay 2008 and December 2017 were analyzed retrospecively. The risk was stratified according to 4 prognostic score systems, the relationship between the 4 prognostic score systems and 3-month early molecular response (3M-EMR), 6 month complete cytogenetic response (6M-CCyR), 12-month major molecular response (12M-MMR) as well as the correlation of the 4 prognostic score systems with deep molecalar response were analyzed. RESULTS: At the end of treatment for 3 months, the EMR was evaluated for 219 patients, among them 164 (74.9%) patients achieved 3M-EMR; at the end of treatment for 6 months, CCyR was evaluated for 180 pathsents, among them 130 (72.2%) patients achicved 6M-CCyR; at the end of treatment for 12 months, the MMR was evaluated for 111 patients, among them 60 (54.1%) patients achieved 12M-MMR. Compared with the high-risk group, the treatment response to IM in the low-risk group (including the low-risk group and the intermediate-risk group) was better. There was significant difference in 3M-EMR according to Sokal score and ELTS score (P＜0.05), and there was significant difference in 12M-MMR according to EUTOS score and ELTS score (P＜0.05). Logistic regression analysis revealed Sokal score (HR=0.69, 95%CI：0.22-1.37, P＜0.05) and 3M-EMR (HR=0.47, 95%CI：0.28-0.84, P＜0.01) independently related with MR4.5, The combination of Sokal score, especially the low risk with 3M-EMR much more can predict MR4.5 (HR=0.42, 95%CI=0.21-0.82, P＜0.01). CONCLUSION: There is a remarkable clinical efficacy of imatinib mesylate on CML-CP patients, moreover, low risk group has a better therapeutic response. Both Sokal score and ELTS score evaluate 3M-EMR better, both EUTOS score and ELTS score evaluate 12M-MMR better. The combination of low risk in Sokal score with 3M-EMR much more can predict MR4.5. The results of this study provide the reference basis for evaluating the clinical therapentic efficacy and timely modifying the therapeutic regimens for CML patients, also possess the reference value for predicting the MR4.5.

Calmodulin Is the Fundamental Regulator of NADK-Mediated NAD Signaling in Plants.

Calcium (Ca2+) signaling and nicotinamide adenine dinucleotide (NAD) signaling are two basic signal regulation pathways in organisms, playing crucial roles in signal transduction, energy metabolism, stress tolerance, and various developmental processes. Notably, calmodulins (CaMs) and NAD kinases (NADKs) are important hubs for connecting these two types of signaling networks, where CaMs are the unique activators of NADKs. NADK is a key enzyme for NADP (including NADP+ and NADPH) biosynthesis by phosphorylating NAD (including NAD+ and NADH) and therefore, maintains the balance between NAD pool and NADP pool through an allosteric regulation mode. In addition, the two respective derivatives from NAD+ (substrate of NADK) and NADP+ (product of NADK), cyclic ADP-ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate (NAADP), have been considered to be the important messengers for intracellular Ca2+ homeostasis which could finally influence the combination between CaM and NADK, forming a feedback regulation mechanism. In this review article, we briefly summarized the major research advances related to the feedback regulation pathway, which is activated by the interaction of CaM and NADK during plant development and signaling. The theories and fact will lay a solid foundation for further studies related to CaM and NADK and their regulatory mechanisms as well as the NADK-mediated NAD signaling behavior in plant development and response to stress.