Advances in metabolism pathways of theaflavins: digestion, absorption, distribution and degradation.

Theaflavins, a major kind of component in black tea, have been reported to show a variety of biological activities and health effects. However, the unstable chemical properties, low bioavailability and unclear metabolism pathways of theaflavins have left much to be desired in terms of its specific efficacy and applications. This paper provides a comprehensive knowledge on the digestion, absorption, metabolism, distribution and excretion of theaflavins. We find that pH-dependent stability, efflux transport proteins are closely related to the low absorption rate and low bioavailability of theaflavins. When pass through the gastrointestinal tract, TFDG, TF2A and TF2B are gradually degraded to TF1, and release gallic acid. Then, the theaflavins skeleton are degraded into small molecular phenolic substances under the action of enzymes and microorganisms. In addition, theaflavins are widely distributed in the human body including brain, lung, heart, kidney, liver, blood tissue in a low content and can be excreted through feces. However, the influence of digestive enzymes barrier and gut microbial barrier on theaflavins are still unclear. Importantly, most findings are reported by in vitro methods and animal experiments, the metabolites and metabolic pathways of theaflavins in human body are not fully understood and need to be further investigated. We hope to lay a theoretical basis for exploring methods to improve the bioavailability of theaflavins and expanding the application of theaflavins in health foods as well as pharmaceuticals.

Two Omics Methods Expose Anti-Depression Mechanism of Raw and Vinegar-Baked Bupleurum Scorzonerifolium Willd.

Bupleurum scorzonerifolium willd. (BS) and its vinegar-baked product (VBS) has been frequently utilized for depression management in clinical Chinese medicine. This paper aims to elucidate the antidepressant mechanism of BS and VBS from the perspectives of metabonomics and gut microbiota. A rat model of depression was established by CUMS combined with feeding alone to evaluate the antidepressant effects of BS and VBS. UPLC-Q-TOF-MS/MS-based metabolomics and 16S rRNA sequencing of rat feces were applied and the correlation of differential metabolic markers and intestinal floras was analyzed. The result revealed that BS and VBS significantly improved depression-like behaviors and the levels of monoamine neurotransmitters in CUMS rats. There were 27 differential endogenous metabolites between CUMS and normal rats, which were involved in 8 metabolic pathways. Whereas, BS and VBS could regulate 18 and 20 metabolites respectively, wherein fifteen of them were shared metabolites. On the genus level, BS and VBS could regulate twenty-five kinds of intestinal floras in CUMS rats, that is, they increased the abundance of beneficial bacteria and decreased the abundance of harmful bacteria. In conclusion, both BS and VBS exert excellent antidepressant effects by regulating various metabolic pathways and ameliorating intestinal microflora dysfunction.

Blocking Gremlin1 inhibits M1 macrophage polarization through Notch1/Hes1 signaling pathway in apical periodontitis.

BACKGROUND: Gremlin1 is a multifunctional protein whose expression is demonstrated to be involved in a series of physiology and pathological processes. The association between Gremlin1 and apcial periodontitis (AP) has been established. M1-polarized macrophages are crucial immune cells that exacerbate the progression of apical periodontal inflammatory response, but the function of Gremlin1 during macrophages activation in periapical lesions is still unclear. This study attempts to explore the regulatory effects of Gremlin1 on macrophage polarization on apical periodontitis microenviroment. METHODS: Clinical specimens were used to determine the expression of Gremlin1 in periapical tissues by immunohistochemical (IHC) staining. Then, the disease models of periapical inflammation in rats were established, and adenovirus- associated virus (AAVs) was used to blockade Gremlin1 expression. Lentivirus carrying sh-Gremlin1 particles were used to transfect THP-1 induced M1-subtype macrophages. To assess the expression of associated molecules, Western-blot, immunofluorescence staining were performed. RESULTS: Gremlin1 was significantly up-regulated in the periapical tissues of subjects with AP as identified by IHC staining, and positively correlated with levels of M1 macrophage-associated genes. Rats AP model with inhibition of Gremlin1 in periapical lesions exhibited limited infiltration of macrophages and decreased expression of M1 macrophage-related genes in periapical lesions. Furthermore, Gremlin1 blockade substantially decreased the Notch1/Hes1 signaling pathway activation level. The in vitro experiments confirmed the above results. CONCLUSION: Taken together, current study illustrated that the Gremlin1 suppression in periapical lesions inhibited M1 macrophage polarization through Notch1/Hes1 axis. Moreover, Gremlin1 may act as a potential candidate in the treatment of AP.

Discovery and verification of anti-inflammatory-related quality markers in the aerial part of Bupleurum scorzonerifolium by UPLC-Q-TOF-MS/MS and in RAW 264.7 cells and a zebrafish model.

INTRODUCTION: The root of Bupleurum scorzonerifolium Willd. (BS) is officially recognized in the Chinese Pharmacopoeia. In contrast, the aerial part of BS (ABS), accounting for 80% of BS, is typically discarded, causing potential waste of medicinal resources. ABS has shown benefits in the treatment of inflammation-related diseases in China and Spain, and the material basis underlying its anti-inflammatory effects must be systematically elucidated for the rational use of ABS. OBJECTIVE: We aimed to screen and validate the anti-inflammatory quality markers (Q-markers) of ABS and to confirm the ideal time for ABS harvesting. METHODS: The chemical components and anti-inflammatory effects of ABS from 10 extracted parts were analyzed by UPLC-Q-TOF-MS/MS and in a lipopolysaccharide (LPS)-induced cell model. Anti-inflammatory substances were screened by Pearson bivariate analysis and gray correlation analysis, and the anti-inflammatory effects were verified in a zebrafish tail-cutting inflammation model. HPLC was applied to measure the Q-marker contents of ABS in different harvesting periods. RESULTS: Ten ABS extracts effectively alleviated the increase in LPS-induced proinflammatory cytokines in RAW 264.7 cells. Forty components were identified from them, among which 27 were common components. Eight components were correlated with anti-inflammatory effects, which were confirmed to reverse the expression of proinflammatory and anti-inflammatory factors in a zebrafish model. Chlorogenic acid, hypericin, rutin, quercetin, and isorhamnetin can be detected by HPLC, and the maximum contents of these five Q-markers were obtained in the sample harvested in August. CONCLUSION: The anti-inflammatory Q-markers of ABS were elucidated by chromatographic-pharmacodynamic-stoichiometric analysis, which served as a crucial basis for ABS quality control.

The Role of Macrophage Efferocytosis in the Pathogenesis of Apical Periodontitis.

Macrophages (Mφs) play a crucial role in the homeostasis of the periapical immune micro-environment caused by bacterial infection. Mφ efferocytosis has been demonstrated to promote the resolution of multiple infected diseases via accelerating Mφ polarization into M2 type. However, the Mφ efferocytosis-apical periodontitis (AP) relationship has not been elucidated yet. This study aimed to explore the role of Mφ efferocytosis in the pathogenesis of AP. Clinical specimens were collected to determine the involvement of Mφ efferocytosis in the periapical region via immunohistochemical and immunofluorescence staining. For a further understanding of the moderator effect of Mφ efferocytosis in the pathogenesis of AP, both an in vitro AP model and in vivo AP model were treated with ARA290, a Mφ efferocytosis agonist. Histological staining, micro-ct, flow cytometry, RT-PCR and Western blot analysis were performed to detect the inflammatory status, alveolar bone loss and related markers in AP models. The data showed that Mφ efferocytosis is observed in the periapical tissues and enhancing the Mφ efferocytosis ability could effectively promote AP resolution via facilitating M2 Mφ polarization. Collectively, our study demonstrates the functional importance of Mφ efferocytosis in AP pathology and highlights that accelerating Mφ efferocytosis via ARA290 could serve as an adjuvant therapeutic strategy for AP.

Sulforaphane attenuates cancer cell-induced atrophy of C2C12 myotubes.

Cancer cachexia is common in many cancers and the loss of skeletal muscle mass compromises the response to therapies and quality of life. A contributing mechanism is oxidative stress and compounds able to attenuate it may be protective. Sulforaphane (SFN), a natural antioxidant in cruciferous vegetables, activates nuclear factor erythroid 2-related factor 2 (Nrf2) signaling to decrease oxidative stress. Although SFN has potential as a cancer therapeutic, whether it can attenuate muscle wasting in the absence or presence of chemotherapy is unknown. In healthy C2C12 myotubes, SFN administration for 48 h induced hypertrophy through increased myoblast fusion via Nrf2 and ERK signaling. To determine whether SFN could attenuate wasting induced by cancer cells, myotubes were cocultured with or without Colon-26 (C-26) cancer cells for 48 h and treated with 5-fluorouracil (5-FU, 5 µM) or vehicle (DMSO). SFN (10 µM) or DMSO was added for the final 24 h. Coculture with cancer cells in the absence and presence of 5-FU reduced myotube width by ∼30% (P < 0.001) and ∼20% (P < 0.01), respectively, which was attenuated by SFN (P < 0.05). Exposure to C-26 conditioned media reduced myotube width by 15% (P < 0.001), which was attenuated by SFN. Western immunoblotting and qRT-PCR confirmed activation of Nrf2 signaling and antioxidant genes. Coadministration of Nrf2 inhibitors (ML-385) or MEK inhibitors (PD184352) revealed that SFN's attenuation of atrophy was blocked by ERK inhibition. These data support the chemoprotective and antioxidative function of SFN in myotubes, highlighting its therapeutic potential for cancer-related muscle wasting.

Core Target and Key Signal Pathway of Xiaoluo in the Treatment of Thyroid Cancer.

Context: At present, hormone therapy and surgery are the main treatments for thyroid cancer, and they have a quick effect but a high recurrence rate. Also, the side effects are significant. it's extremely urgent to explore treatments that can take into account both therapeutic benefits and side effects. Objective: The study intended to explore whether Xiaoluo has an inhibitory effect on the proliferation of thyroid-cancer cells in vitro and to examine the core target and key signaling pathway of Xiaoluo in the treatment of thyroid cancer, using the thyroid-cancer cell line SW579. Design: The research team performed an in-vitro study. Setting: The study took place at the College of Pharmacy at Harbin University of Commerce in Harbin, China. Outcome Measures: The research team used a Western blot analysis to detect the expression of apoptosis proteins-B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), and Caspase-3-and the activity related to the signaling pathways phosphoinositide 3-kinase (PI3K)/ protein kinase B (AKT)/ mammalian target of rapamycin 1 (mTORC1). The team measured optical densities and inhibition rates for the 1, 2, 5, 10, and 15 mg/mL Xiaokuo groups and for a negative control group. The research team measured apoptosis, expression of Bcl-2, Bax, and Caspase-3, and expression of P13K, AKT, and mTor for the 10 µmol/L LY294002, 10 mg/mL Xiaoluo, 100 ng/mL IGF-1, and 100 ng/mL IGF-1+10 mg/mL Xiaoluo groups and for the blank control group. Results: The inhibition of SW579 cell proliferation increased with each increase in the Xiaoluo concentration from 1-15 mg/mL, and the inhibition rate reached 49.63% when the concentration was 15 mg/ml. The Xiaoluo group's late and total apoptosis rates were significantly higher (both P < .01) than those of the blank control group. The Xiaoluo group's expression of the Bcl-2 protein was significantly lower (P < .05), and its expressions of Bax and Caspase-3 were significantly higher (both P < .01) than those of the blank control group. The Xiaoluo group's expressions of P-PI3K, P-Akt, and P-MTOR were significantly lower than those of the blank group (all P < .01). These findings were comparable to those that occurred with use of the PI3K/AKT/mTORC1 signaling pathway inhibitor LY294002. Conclusions: Xiaoluo exerts its antithyroid-cancer effects through the induction of apoptosis in thyroid cancer cells through the inhibition of the PI3K/AKT/mTORC1 signaling pathway. Xiaoluo may serve as a potential therapeutic agent for the treatment of thyroid cancer.

Gene-coexpression network analysis identifies specific modules and hub genes related to cold stress in rice.

BACKGROUND: When plants are subjected to cold stress, they undergo a series of molecular and physiological changes to protect themselves from injury. Indica cultivars can usually withstand only mild cold stress in a relatively short period. Hormone-mediated defence response plays an important role in cold stress. Weighted gene co-expression network analysis (WGCNA) is a very useful tool for studying the correlation between genes, identifying modules with high phenotype correlation, and identifying Hub genes in different modules. Many studies have elucidated the molecular mechanisms of cold tolerance in different plants, but little information about the recovery process after cold stress is available. RESULTS: To understand the molecular mechanism of cold tolerance in rice, we performed comprehensive transcriptome analyses during cold treatment and recovery stage in two cultivars of near-isogenic lines (9311 and DC907). Twelve transcriptomes in two rice cultivars were determined. A total of 2509 new genes were predicted by fragment splicing and assembly, and 7506 differentially expressed genes were identified by pairwise comparison. A total of 26 modules were obtained by expression-network analysis, 12 of which were highly correlated with cold stress or recovery treatment. We further identified candidate Hub genes associated with specific modules and analysed their regulatory relationships based on coexpression data. Results showed that various plant-hormone regulatory genes acted together to protect plants from physiological damage under short-term low-temperature stress. We speculated that this may be common in rice. Under long-term cold stress, rice improved the tolerance to low-temperature stress by promoting autophagy, sugar synthesis, and metabolism. CONCLUSION: Through WGCNA analysis at the transcriptome level, we provided a potential regulatory mechanism for the cold stress and recovery of rice cultivars and identified candidate central genes. Our findings provided an important reference for the future cultivation of rice strains with good tolerance.

Genome wide association analysis for yield related traits in maize.

BACKGROUND: Understanding the genetic basis of yield related traits contributes to the improvement of grain yield in maize. RESULTS: Using 291 excellent maize inbred lines as materials, six yield related traits of maize, including grain yield per plant (GYP), grain length (GL), grain width (GW), kernel number per row (KNR), 100 kernel weight (HKW) and tassel branch number (TBN) were investigated in Jinan, in 2017, 2018 and 2019. The average values of three environments were taken as the phenotypic data of yield related traits, and they were statistically analyzed. Based on 38,683 high-quality SNP markers in the whole genome of the association panel, the MLM with PCA model was used for genome-wide association analysis (GWAS) to obtain 59 significantly associated SNP sites. Moreover, 59 significantly associated SNPs (P < 0.0001) referring to GYP, GL, GW, KNR, HKW and TBN, of which 14 SNPs located in yield related QTLs/QTNs previously reported. A total of 66 candidate genes were identified based on the 59 significantly associated SNPs, of which 58 had functional annotation. CONCLUSIONS: Using genome-wide association analysis strategy to identify genetic loci related to maize yield, a total of 59 significantly associated SNP were detected. Those results aid in our understanding of the genetic architecture of maize yield and provide useful SNPs for genetic improvement of maize.

Functional analysis revealed the involvement of ZmABCB15 in resistance to rice black-streaked dwarf virus infection.

BACKGROUND: Maize rough dwarf disease (MRDD), caused by rice black-streaked dwarf virus (RBSDV) belonging to the Fijivirus genus, seriously threatens maize production worldwide. Three susceptible varieties (Ye478, Zheng 58, and Zhengdan 958) and two resistant varieties (P138 and Chang7-2) were used in our study. RESULTS: A set of ATP-binding cassette subfamily B (ABCB) transporter genes were screened to evaluate their possible involvements in RBSDV resistance. In the present study, ZmABCB15, an ABCB transporter family member, was cloned and functionally identified. Expression analysis showed that ZmABCB15 was significantly induced in the resistant varieties, not in the susceptible varieties, suggesting its involvement in resistance to the RBSDV infection. ZmABCB15 gene encodes a putative polar auxin transporter containing two trans-membrane domains and two P-loop nucleotide-binding domains. Transient expression analysis indicated that ZmABCB15 is a cell membrance localized protein. Over-expression of ZmABCB15 enhanced the resistance by repressing the RBSDV replication ratio. ZmABCB15 might participate in the RBSDV resistance by affecting the homeostasis of active and inactive auxins in RBSDV infected seedlings. CONCLUSIONS: Polar auxin transport might participate in the RBSDV resistance by affecting the distribution of endogenous auxin among tissues. Our data showed the involvement of polar auxin transport in RBSDV resistance and provided novel mechanism underlying the auxin-mediated disease control technology.

Effects of sulfamethoxazole on aerobic sludge granulation process.

AIMS: Our purpose was to clarify the effect of sulfamethoxazole (SMX) on the start-up period, particle formation, and treatment efficiency of an aerobic granular sludge system. METHODS AND RESULTS: We compared an R1 granular sequencing batch reactor (GSBR) started with 5 µg L-1 SMX and an R2 GSBR started without SMX, as a control, to investigate the impact of a trace amount of SMX (5 µg L-1 ) on aerobic granular sludge (AGS) characteristics and the removal of conventional contaminants. AGS granulation in the R1 system was not inhibited by SMX, but the granule particle size was smaller than that in the R2 system. Both systems had good performance removing conventional pollutants. Extracellular polymeric substance secretion in the R1 system was lower than that in the R2 system. After stabilizing reactor operations, the SMX removal efficiency in the R1 system (~73.93%) was higher than that in the R2 system (~70.66%). The start-up modes also determined the differences in the microbial community structure of the AGS systems. CONCLUSIONS: SMX-activated AGS performed better than AGS without SMX. SIGNIFICANCE AND IMPACT OF STUDY: The study can help engineers determine start-up modes with varieties of antibiotics in AGS processes and provide references for the optimization of water treatment processes.

A new cyclic peptide from Selaginella tamariscina.

A new cyclic peptide selapeptin B (1), together with one known nor-lignan glycoside moellenoside C (2), was isolated from Selaginella tamariscina. The structures of 1 and 2 were elucidated on the basis of chemical and spectral analysis, including 1D, 2D NMR analyses and HRESIMS. Two compounds were evaluated for cytotoxic activities against B16F10, MDA-MB-231, and MDA-MB-468 cell lines by MTT assay. Compound 1 showed the potent activity against B16F10 melanoma cell lines.

Two new flavonol glycosides from Selaginella tamariscina.

Two new flavonol glycosides 3,5,7-trimethoxyflavone-4'-O-[5'''-O-p-coumaroyl-ß-D-apiofuranoyl-(1'''→2'')-ß-D-glucopyranoside] (1) and 3,5,7-trimethoxyflavone -4'-O-ß-D-glucopyranoside (2) were isolated from Selaginella tamariscina. The structures of 1 and 2 were elucidated on the basis of chemical and spectral analysis, including 1D, 2D NMR analyses and HRESIMS spectrometry. Two compounds were evaluated for cytotoxic activities against A-375, MCF-7, MDA-MB-231 and MDA-MB-468 cell lines by MTT assay. Unfortunately, two compounds displayed no cytotoxic activities.

[Mechanism of Bupleurum scorzonerifolium and Paeonia lactiflora herbal pair against liver cancer: an exploration based on UPLC-Q-TOF-MS combined with network pharmacology].

This study aimed to decipher the pharmacodynamic material basis and mechanism of herbal pair Bupleurum scorzonerifolium-Paeonia lactiflora(BS-PL) against liver cancer based on UPLC-Q-TOF-MS and network pharmacology. MTT assay and human hepatocellular carcinoma HepG2 cells were used to screen the effective part of BS-PL, the active components of which were further analyzed and identified by UPLC-Q-TOF-MS. Next, we applied Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) to screen the active ingredients with OB≥30%. Then TCMSP and SwissTargetPrediction were used to collect and predict component targets, followed by the search of liver cancer-related targets with GeneCards and DisGeNET. The intersection targets were obtained using Venny 2.1.0. Protein-protein interaction(PPI) network was constructed using STRING to uncover the core targets, which were subjected to Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis based on DAVID. Finally, the effects of active ingredients on the expression of main proteins enriched in the key pathways of HepG2 cells were verified by Western blot. The results indicated that compared with 30%, 50%, and 70% ethanol extracts of BS-PL, the n-butanol extraction part(CSYZ) from 95% ethanol extract of BS-PL exhibited the best anti-tumor effect. UPLC-Q-TOF-MS revealed 31 ingredients, 14 of which showed OB≥30%. A total of 220 intersection targets were obtained, from which 35 were selected as the key targets under the condition of two times the median of degree. Among the 215 items with P<0.05 obtained through GO enrichment analysis, 154 were classified into biological processes, 22 into cell components and 39 into molecular functions. KEGG enrichment analysis revealed 95 significantly affected signaling pathways, and the ones(sorted in a descending order by P value) closely related to the anti-liver cancer effect of herbal pair were PI3 K-AKT signaling pathway, TNF signaling pathway, MAPK signaling pathway, HIF-1 signaling pathway, and ErbB signaling pathway. Finally, the PI3 K/AKT signaling pathway involving the largest number of targets was extrapolated, and it was found that this pathway contained 15 core targets and 8 active components. Experimental verification showed that the effective components of BS-PL significantly inhibited the expression of p-PI3 K and p-AKT, consistent with the prediction results of network pharmacology. In conclusion, the main pharmacodynamic substances of BS-PL against liver cancer are 14 components like saikosaponin a, saikosaponin d, and paeoniflorin, which exert the anti-liver cancer effect by regulating PI3 K/AKT pathway.

Efficiency of sulfamethoxazole removal from wastewater using aerobic granular sludge: influence of environmental factors.

The effects of adsorption, sulfamethoxazole (SMX) content, chemical oxygen demand (COD), and dissolved oxygen (DO) are recognized to be crucial for SMX removal in the aerobic granular sludge (AGS) system. Therefore, we investigated the impact of adsorption and these three different environmental factors on the SMX removal loading rate and removal efficiency of an AGS system, and determined the differences in microbial community composition under different environmental conditions. Adsorption was not the main SMX removal mechanism, as it only accounted for 5% of the total removal. The optimal SMX removal conditions were obtained for AGS when the COD, DO, and SMX concentrations were 600 mg/L, 8 mg/L, and 2,000 µg/L, respectively. The highest SMX removal efficiency was 93.53%. Variations in the three environmental factors promoted the diversity and changes of microbial communities in the AGS system. Flavobacterium, Thauera, and norank_f_Microscillaceae are key microorganisms in the AGS system. Thauera, and norank_f_Microscillaceae were sensitive to increases in SMX concentrations and beneficial for degrading high SMX concentrations. In particular, Flavobacterium abundances gradually decreased with increasing SMX concentrations.

Two new selariscinins from Selaginella tamariscina (Beauv.) Spring.

Two new selariscinins named selariscinin F (1) and selariscinin G (2), along with one known selariscinin D (3) were isolated from Selaginella tamariscina. The structures of 1-3 were elucidated on the basis of chemical and spectral analysis, including 1D, 2D NMR analyses and HRESIMS.

Circular RNA circCCDC9 alleviates ischaemic stroke ischaemia/reperfusion injury via the Notch pathway.

Stroke is a leading cause of death and disability, while its pathophysiological mechanisms are not fully understood. In this study, we used the tMCAO mice model to investigate the role of circCCDC9 in the pathogenesis of stroke. We found that the expression of circCCDC9 was significantly decreased in the brains of tMCAO mice. The Evens blue and brain water content were significantly higher in the Pre-IR and Pre-IR+Vector mice, while these patterns were partially reversed by overexpression of circCCDC9. The nitrite content and eNOS expression were decreased in the Pre-IR and Pre-IR+Vector groups, which was restored by circCCDC9 overexpression. Overexpression of circCCDC9 also inhibited the expression of Caspase-3, Bax/Bcl-2 ratio and the expression of Notch1, NICD and Hes1 in tMCAO mice. Knockdown of circCCDC9 increased the expression of Caspase-3, Bax/Bcl-2 ratio and the expression of Notch1, NICD and Hes1. In summary, overexpression of circCCDC9 protected the blood-brain barrier and inhibited apoptosis by suppressing the Notch1 signalling pathway, while knockdown of circCCDC9 had the opposite effects. Our findings showed that circCCDC9 is a potential novel therapeutic target for cerebrovascular protection in acute ischaemic stroke.

Expression of CCL-18 and CX3CL1 in Serum, and Their Potential Roles as Two Diagnostic and Prognostic Markers in Chronic Obstructive Pulmonary Disease and Chronic cor Pulmonale (COPD&CCP): a Pilot Study.

BACKGROUND: CC chemokine ligand-18 (CCL-18) and CX3 chemokine ligand 1 (CX3CL1) are key factors of vascular and tissue injury in chronic respiratory diseases. Here, we investigated the value of CCL-18 and CX3CL1 in diagnosis and prognosis of patients with chronic obstructive pulmonary disease and chronic cor pulmonale (COPD&CCP). METHODS: First, we investigated the expression profile of CCL-18 and CX3CL1 in serum of COPD&CCP patients. Then the relationship of the level of CCL-18 and CX3CL1 with clinicopathological characteristics was analyzed. Subsequently, we evaluated the diagnostic accuracy of CCL-18 and CX3CL1 to discriminate COPD&CCP. The prognostic value and therapy outcome were also evaluated. RESULTS: Compared to healthy subjects, the level of CCL-18 (8.01 ± 2.01 ng/mL) and CX3CL1 (2,096.11 ± 306.09 ng/mL) was significantly increased in COPD&CCP patients (p < 0.05). The upregulation of CCL-18 and CX3CL1 was significantly correlated with clinicopathological characteristics including CRP, IL-6, FIB, NT-proBNP, FEV1, FEV1/FVC, PASP, LVEF, and T wave anomaly. The combination of CCL-18 and CX3CL1 showed high precision for discriminating COPD&CCP with high AUC values (0.828), sensitivity (66.1%), and specificity (92.5%). Furthermore, CCL-18 and CX3CL1 acted as independent factors which lead to poor clinical benefits and indicated poor prognosis of COPD&CCP patients. CONCLUSIONS: Taken together, our results indicated that CCL-18 and CX3CL1 could act as suitable biomarkers in prognosis and prognostic evaluation of COPD&CCP.

Genomic selection on shelling percentage and other traits for maize.

Genomic selection (GS) is the one of the new method for molecular marker-assisted selection (MAS) that can improve selection efficiency and thereby accelerate selective breeding progress. In the present study, we used the exotic germplasm LK1 to improve the shelling percentage of Qi319 by GS. Genome-wide marker effects for each trait were estimated based on the performance of the testcross and SNP data for F2 progenies in the training population. The accuracy of genomic predictions was estimated as the correlation between marker-predicted genotypic values and phenotypic values of the testcrosses for each trait in the validation population. Our study result indicated that selection response for shell percentage was 33.7%, which is greater than those for grain yield, kernel number per ear, or grain moisture at harvest. Selection response for tassel branch number and weight per 100 kernels was greater than 60%. The Higher trait heritability resulted in better prediction efficiency; Prediction accuracy increased with the training population size; Prediction efficiency did not differ significantly between SNP densities of 1000 bp and 55,000 bp. The results of the present research project will provide a basis for genome-wide selection technology in maize breeding, and lay the groundwork for the application of GS to germplasms that are useful in China.

Expression analysis of genes encoding double B-box zinc finger proteins in maize.

The B-box proteins play key roles in plant development. The double B-box (DBB) family is one of the subfamily of the B-box family, with two B-box domains and without a CCT domain. In this study, 12 maize double B-box genes (ZmDBBs) were identified through a genome-wide survey. Phylogenetic analysis of DBB proteins from maize, rice, Sorghum bicolor, Arabidopsis, and poplar classified them into five major clades. Gene duplication analysis indicated that segmental duplications made a large contribution to the expansion of ZmDBBs. Furthermore, a large number of cis-acting regulatory elements related to plant development, response to light and phytohormone were identified in the promoter regions of the ZmDBB genes. The expression patterns of the ZmDBB genes in various tissues and different developmental stages demonstrated that ZmDBBs might play essential roles in plant development, and some ZmDBB genes might have unique function in specific developmental stages. In addition, several ZmDBB genes showed diurnal expression pattern. The expression levels of some ZmDBB genes changed significantly under light/dark treatment conditions and phytohormone treatments, implying that they might participate in light signaling pathway and hormone signaling. Our results will provide new information to better understand the complexity of the DBB gene family in maize.