Genetic Variability of CYP4F2, CYP2D6, CYP2E1, and ACE in the Chinese Yi Population.

Genetic polymorphisms of very important pharmacogenes (VIP) are a significant factor contributing to inter-individual variability in drug therapy. The purpose of this study was to identify significantly different loci in the Yi population and to enrich their pharmacogenomic information. 54 VIP variants were selected from the Pharmacogenomics Knowledge Base (PharmGKB) and genotyped in 200 Yi individuals. Then, we compared their genotype distribution between the Yi population and the other 26 populations using the χ2 test. Compared with the other 26 populations, the genotype frequencies of 4 single nucleotide polymorphisms (SNPs), rs2108622 (CYP4F2), rs1065852 (CYP2D6), rs2070676 (CYP2E1), and rs4291 (ACE), had significant differences in the Yi population. For example, the TT genotype frequency of rs2108622 (8.1%) was higher than that of African populations, and the AA genotype frequency of rs1065852 (27.3%) was higher than that of other populations except East Asians. We also found that the Yi populations differed the least from East Asians and the most from Africans. Furthermore, the differences in these variants might be related to the effectiveness and toxicity risk of using warfarin, iloperidone, cisplatin cyclophosphamide, and other drugs in the Yi population. Our data complement the pharmacogenomic information of the Yi population and provide theoretical guidance for their personalized treatment.

Genetic polymorphisms of pharmacogenomic VIP variants in the Hui population from Ningxia Province of China.

Pharmacogenomics has been widely used to study the very important pharmacogenetic (VIP) variants among different populations. However, there is little pharmacogenomic information about the Chinese Hui population. Our research aimed to reveal the outstandingly different loci in the Hui population, and provide a theoretical foundation for personalized drug use in the Hui population, so as to facilitate more effective treatment of diseases. This study genotyped 53 VIP variants of 26 genes in 200 independent Hui individuals based on the Pharmacogenetics and Pharmacogenomics Knowledge Base (PharmGKB). Remarkable differences in the genotype and allele frequencies between the Hui and 26 other populations from the 1000 Genomes Project were assessed using the χ2 test. The genotype and allele frequencies of single nucleotide polymorphisms (SNPs) in PTGS2 (rs20417), NAT2 (rs1801280), NAT2 (rs1208), ACE (rs4291), and CYP2D6 (rs1065852) were considerably different in the Hui population compared with those in the other 26 populations. Besides, using the PharmGKB database, we identified several VIP variants that may alter the drug metabolism of ibuprofen, rofecoxib (PTGS2), captopril (ACE), citalopram, and escitalopram (CYP2D6). We also discovered other variants associated with adverse reactions to cisplatin and cyclophosphamide (NAT2). Our study indicated that the loci of PTGS2 (rs20417), NAT2 (rs1801280 and rs1208), ACE (rs4291), and CYP2D6 (rs1065852) in the Hui population were obviously different from those in the other 26 populations, which provides reliable information for predicting drug efficacy. Besides, it supplements the pharmacogenomic knowledge of the Hui population and lays the foundation for the individualized treatment for the Hui population.

Modifying the Fiber Structure and Filtration Performance of Polyester Materials Based on Two Different Preparation Methods.

How to build a satisfactory indoor environment has become increasingly important. In this paper, the synthesis and improvement of the most widely used polyester materials in China were carried out based on two different preparation methods, and the structures and filtration performances were tested and analyzed. The results showed that a carbon black coating was wrapped on the surfaces of the new synthetic polyester filter fibers. Compared with the original materials, the filtration efficiencies of PM10, PM2.5, and PM1 were increased by 0.88-6.26, 1.68-8.78, and 0.42-4.84%, respectively. The best filtration velocity was 1.1 m/s, and the new synthetic polyester materials with direct impregnation demonstrated superior filtration performance. The filtration efficiency of the new synthetic polyester materials was improved on the particulates with sizes of 1.0-5.0 µm. The filtration performance of G4 was better than that of G3. The filtration efficiencies of PM10, PM2.5, and PM1 were improved by 4.89, 4.20, and 11.69%, respectively. The quality factor value can be used to assess the comprehensive filtration performance of air filters in practical applications. It could provide reference values for the selection of synthetic methods of new filter materials.

DLGAP5 Regulates the Proliferation, Migration, Invasion, and Cell Cycle of Breast Cancer Cells via the JAK2/STAT3 Signaling Axis.

The aim of this study was to discover new biomarkers to detect breast cancer (BC), which is an aggressive cancer with a high mortality rate. In this study, bioinformatic analyses (differential analysis, weighted gene co-expression network analysis, and machine learning) were performed to identify potential candidate genes for BC to study their molecular mechanisms. Furthermore, Quantitative Real-time PCR and immunohistochemistry assays were used to examine the protein and mRNA expression levels of a particular candidate gene (DLGAP5). And the effects of DLGAP5 on cell proliferation, migration, invasion, and cell cycle were further assessed using the Cell Counting Kit-8 assay, colony formation, Transwell, wound healing, and flow cytometry assays. Moreover, the changes in the JAK2/STAT3 signaling-pathway-related proteins were detected by Western Blot. A total of 44 overlapping genes were obtained by differential analysis and weighted gene co-expression network analysis, of which 25 genes were found in the most tightly connected cluster. Finally, NEK2, CKS2, UHRF1, DLGAP5, and FAM83D were considered as potential biomarkers of BC. Moreover, DLGAP5 was highly expressed in BC. The down-regulation of DLGAP5 may inhibit the proliferation, migration, invasion, and cell cycle of BC cells, and the opposite was true for DLGAP5 overexpression. Correspondingly, silencing or overexpression of the DLGAP5 gene inhibited or activated the JAK2/STAT3 signaling pathway, respectively. DLGAP5, as a potential biomarker of BC, may impact the cell proliferation, migration, invasion, cell cycle, and BC development by modulating the JAK2/STAT3 signaling pathway.

Identification and Characterization of AP2/ERF Transcription Factors in Yellow Horn.

The AP2/ERF gene family involves numerous plant processes, including growth, development, metabolism, and various plant stress responses. However, several studies have been conducted on the AP2/ERF gene family in yellow horn, a new type of oil woody crop and an essential oil crop in China. According to sequence alignment and phylogenetic analyses, one hundred and forty-five AP2/ERF genes were detected from the yellow horn genome. They were divided into four relatively conserved subfamilies, including 21 AP2 genes, 119 ERBP genes, 4 RAV genes, and 1 Soloist gene. Gene analysis of XsAP2/ERF TFs showed 87 XsAP2/ERF TFs lacked introns. There were 75 pairs of collinearity relationships between X. sorbifolium and Arabidopsis, indicating a close similarity. In addition, the expression patterns of XsAP2/ERF TFs under cold treatments confirmed that the XsAP2/ERF TFs play essential roles in abiotic stress response. The expression of eight XsAP2/ERF transcription factors was verified in different tissues and under various stress treatments using RT-qPCR. This study establishes a starting point for further research to explore the potential mechanisms of identifying candidate AP2/ERF TFs that could respond to the abiotic stress of yellow horn.

Inhibiting role of rosiglitazone in the regulation of inflammatory response and protective effects for severe acute pancreatitis in mice.

OBJECTIVES: Our study aimed to probe the effects of rosiglitazone treatment on a severe acute pancreatitis (SAP) model induced by caerulein and investigate the underlying mechanism. METHODS: Differentially expressed messenger RNAs (mRNAs) in the mice of a SAP group were screened out by microarray analysis. The inflammatory response pathway was obtained from the online website DAVID Bioinformatics Resources 6.8. The interactions of caerulein and its target proteins were shown by search tool for interactions of chemicals (STITCH). Functional interactions of the genes associated with pancreatitis and the target proteins of caerulein were obtained with search tool for interactions of chemicals (STRING). SAP mice were established by hourly intraperitoneal injection of caerulein. Rosiglitazone was used as treatment drug, and pancreatic inflammation was assessed. The expression of Socs3 was studied by reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot analysis. The expression of interleukin (IL)-6, IL-1b, and Egr1 were studied by RT-PCR and Western blot analysis. RESULTS: The GSE77983 data were analyzed, and the results showed that Socs3 was overexpressed in SAP tissues. The inflammation response pathway in pancreas was selected by DAVID, STITCH, and STRING. After injection of rosiglitazone in mice, the serum levels of amylase and lipase were decreased. Furthermore, the mRNA and protein levels of Socs3 and inflammatory cytokines in pancreatic tissues were downregulated. CONCLUSIONS: Rosiglitazone could protect mice with SAP from injury by downregulating Socs3 and inhibiting the inflammatory response pathway.

Interleukin receptor activates a MYD88-ARNO-ARF6 cascade to disrupt vascular stability.

The innate immune response is essential for combating infectious disease. Macrophages and other cells respond to infection by releasing cytokines, such as interleukin-1ß (IL-1ß), which in turn activate a well-described, myeloid-differentiation factor 88 (MYD88)-mediated, nuclear factor-κB (NF-κB)-dependent transcriptional pathway that results in inflammatory-cell activation and recruitment. Endothelial cells, which usually serve as a barrier to the movement of inflammatory cells out of the blood and into tissue, are also critical mediators of the inflammatory response. Paradoxically, the cytokines vital to a successful immune defence also have disruptive effects on endothelial cell-cell interactions and can trigger degradation of barrier function and dissociation of tissue architecture. The mechanism of this barrier dissolution and its relationship to the canonical NF-κB pathway remain poorly defined. Here we show that the direct, immediate and disruptive effects of IL-1ß on endothelial stability in a human in vitro cell model are NF-κB independent and are instead the result of signalling through the small GTPase ADP-ribosylation factor 6 (ARF6) and its activator ARF nucleotide binding site opener (ARNO; also known as CYTH2). Moreover, we show that ARNO binds directly to the adaptor protein MYD88, and thus propose MYD88-ARNO-ARF6 as a proximal IL-1ß signalling pathway distinct from that mediated by NF-κB. Finally, we show that SecinH3, an inhibitor of ARF guanine nucleotide-exchange factors such as ARNO, enhances vascular stability and significantly improves outcomes in animal models of inflammatory arthritis and acute inflammation.

Plasma Membrane-Localized Calcium Pumps and Copines Coordinately Regulate Pollen Germination and Fertility in Arabidopsis.

Calcium plays an important role in plant growth, development, and response to environmental stimuli. Copines are conserved plasma membrane-localized calcium-binding proteins which regulate plant immune responses and development. In this study, we found that copine proteins BON2 and BON3, the paralogs of BON1, physically interact with calcium pumps ACA8 and ACA10 in Arabidopsis. Notably, ACA9, the closest homologue of ACA8 and ACA10 functioning in pollen tube growth, interacts with all three copines. This is consistent with the protein⁻protein interactions between the two protein families, the aca8, aca10, aca8/aca10, bon1/2/3 mutants as well as aca9 mutant exhibited defects on pollen germination and seed production. Taken together, plasma membrane-localized interacting calcium pumps and copines coordinately control pollen tube growth, likely through manipulating calcium efflux.

An Energetic Guide for Estimating Trifluoromethyl Cation Donor Abilities of Electrophilic Trifluoromethylating Reagents: Computations of X-CF3 Bond Heterolytic Dissociation Enthalpies.

This work established an energetic guide for estimating the trifluoromethyl cation-donating abilities (TC(+)DA) of electrophilic trifluoromethylating reagents through computing X-CF3 bond (X = O, S, Se, Te, and I) heterolytic dissociation enthalpies. TC(+)DA values for a wide range of popular reagents were derived on the basis of density functional calculations (M06-2X). A good correspondence has been identified between the computed TC(+)DA values and the experimentally observed relative trifluoromethylating capabilities of the reagents. Substituent effects hold good linear free energy relationships on the TC(+)DAs of the most widely used reagents including Umemoto reagent, Yagupolskii-Umemoto reagent, and Togni reagents, which allow their trifluoromethylating capabilities to be rationally tuned by substituents and thus extend their synthetic utility. All the information disclosed in this work would contribute to future rational exploration of the electrophilic trifluoromethylation chemistry.

Response of bacterial community structure to different phosphorus additions in a tobacco-growing soil.

Introduction: Phosphorus (P), which plays a vital role in plant growth, is continually added to soil to maximize biomass production, leading to excessive P accumulation and water eutrophication. Results: In this study, a pot experiment using a subtropical tobacco-growing soil fertilized with four P levels-no P, low P, medium P, and high P-was conducted and rhizosphere and bulk soils were analyzed. Results: P addition significantly increased tobacco biomass production (except under low P input) and total soil P and available P content (P<0.05), whereas total nitrogen content decreased in the rhizosphere soils, although this was only significant with medium P application. P fertilization also significantly altered the bacterial communities of rhizosphere soils (P<0.05), but those of bulk soils were unchanged (P>0.05). Moreover, a significant difference was found between rhizosphere soils with low (LR) and high (HR) P inputs (P<0.05). Additionally, compared with rhizosphere soils with no P (CKR), Shannon diversity showed a declining trend, which was significant with LR and HR (P<0.05), whereas an increasing tendency was observed for Chao1 diversity except in LR (P>0.05). Functional prediction revealed that P application significantly decreased the total P and N metabolism of microorganisms in rhizosphere soils (P<0.05). Discussion: Collectively, our results indicate that maintaining sustainable agricultural ecosystems under surplus P conditions requires more attention to be directed toward motivating the potential of soil functional microbes in P cycling, rather than just through continual P input.

Very important pharmacogenetic variants landscape and potential clinical relevance in the Zhuang population from Yunnan province.

The gradual evolution of pharmacogenomics has shed light on the genetic basis for inter-individual drug response variations across diverse populations. This study aimed to identify pharmacogenomic variants that differ in Zhuang population compared with other populations and investigate their potential clinical relevance in gene-drug and genotypic-phenotypic associations. A total of 48 variants from 24 genes were genotyped in 200 Zhuang subjects using the Agena MassARRAY platform. The allele frequencies and genotype distribution data of 26 populations were obtained from the 1000 Genomes Project, followed by a comparison and statistical analysis. After Bonferroni correction, significant differences in genotype frequencies were observed of CYP3A5 (rs776746), ACE (rs4291), KCNH2 (rs1805123), and CYP2D6 (rs1065852) between the Zhuang population and the other 26 populations. It was also found that the Chinese Dai in Xishuangbanna, China, Han Chinese in Beijing, China, and Southern Han Chinese, China showed least deviation from the Zhuang population. The Esan in Nigeria, Gambian in Western Division, The Gambia, and Yoruba in Ibadan, Nigeria exhibited the largest differences. This was also proved by structural analysis, Fst analysis and phylogenetic tree. Furthermore, these differential variants may be associated with the pharmacological efficacy and toxicity of Captopril, Amlodipine, Lisinopril, metoclopramide, and alpha-hydroxymetoprolol in the Zhuang population. Our study has filled the gap of pharmacogenomic information in the Zhuang population and has provided a theoretical framework for the secure administration of drugs in the Zhuang population.

The landscape of very important pharmacogenes variants and potential clinical relevance in the Chinese Jingpo population: a comparative study with worldwide populations.

BACKGROUND: Pharmacogenomics is a facet of personalized medicine that explores how genetic variants affect drug metabolism and adverse drug reactions. Therefore, this study aims to detect distinct pharmacogenomic variations among the Jingpo population and explore their clinical correlation with drug metabolism and toxicity. METHODS: Agena MassARRAY Assay was used to genotype 57 VIP variants in 28 genes from 159 unrelated Jingpo participants. Subsequently, the chi-squared test and Bonferroni's statistical tests were utilized to conduct a comparative analysis of genotypes and allele frequencies between the Jingpo population and the other 26 populations from the 1000 Genome Project. RESULTS: We discovered that the KHV (Kinh in Ho ChiMinh City, Vietnam), CHS (Southern Han Chi-nese, China) and JPT (Japanese in Tokyo, Japan) exhibited the smallest differences from the Jingpo with only 4 variants, while ESN (Esan in Nigeria) exhibited the largest differences with 30 variants. Besides, a total of six considerably different loci (rs4291 in ACE, rs20417 in PTGS2, rs1801280 and rs1799929 in NAT2, rs2115819 in ALOX5, rs1065852 in CYP2D6, p < 3.37 × 10-5) were identified in this study. According to PharmGKB, rs20417 (PTGS2), rs4291 (ACE), rs2115819 (ALOX5) and rs1065852 (CYP2D6) were found to be associated with the metabolism efficiency of non-steroidal anti-inflammatory drugs (NSAIDs), aspirin, montelukast and tamoxifen, respectively. Meanwhile, rs1801280 and rs1799929 (NAT2) were found to be related to drug poisoning with slow acetylation. CONCLUSION: Our study unveils distinct pharmacogenomic variants in the Jingpo population and discovers their association with the metabolic efficiency of NSAIDs, montelukast, and tamoxifen.

Effects of drought stress on photosynthetic physiological characteristics, leaf microstructure, and related gene expression of yellow horn.

Yellow horn grows in northern China and has a high tolerance to drought and poor soil. Improving photosynthetic efficiency and increasing plant growth and yield under drought conditions have become important research content for researchers worldwide. Our study goal is to provide comprehensive information on photosynthesis and some candidate genes breeding of yellow horn under drought stress. In this study, seedlings' stomatal conductance, chlorophyll content, and fluorescence parameters decreased under drought stress, but non-photochemical quenching increased. The leaf microstructure showed that stomata underwent a process from opening to closing, guard cells from complete to dry, and surrounding leaf cells from smooth to severe shrinkage. The chloroplast ultrastructure showed that the changes of starch granules were different under different drought stress, while plastoglobules increased and expanded continuously. In addition, we found some differentially expressed genes related to photosystem, electron transport component, oxidative phosphate ATPase, stomatal closure, and chloroplast ultrastructure. These results laid a foundation for further genetic improvement and deficit resistance breeding of yellow horn under drought stress.

Identification and characterization of lipoxygenase (LOX) genes involved in abiotic stresses in yellow horn.

Lipoxygenase (LOX) gene plays an essential role in plant growth, development, and stress response. 15 LOX genes were identified, which were unevenly distributed on chromosomes and divided into three subclasses in this study. In promoter region analysis, many cis-elements were identified in growth and development, abiotic stress response, hormonal response, and light response. qRT-PCR showed that the LOX gene showed tissue specificity in seven tissues, especially XsLOX1, 3, and 7 were relatively highly expressed in roots, stems, and axillary buds. The different expression patterns of LOX genes in response to abiotic stress and hormone treatment indicate that different XsLOX genes have different reactions to these stresses and play diversified roles. This study improves our understanding of the mechanism of LOX regulation in plant growth, development, and stress and lays a foundation for further analysis of biological functions.

Leaf nutrient resorption of two life-form tree species in urban gardens and their response to soil nutrient availability.

Background: Leaf nutrient resorption is a key strategy in plant conservation that minimizes nutrient loss and enhances productivity. However, the differences of the nutrient resorption among garden tree species in urban ecosystems were not clearly understood, especially the differences of nitrogen resorption efficiency (NRE) and phosphorous resorption efficiency (PRE) between evergreen and deciduous trees. Methods: We selected 40 most generally used garden tree specie belonged two life forms (evergreen and deciduous) and investigated the nitrogen (N) and phosphorus (P) concentrations in green and senesced leaves and soil nutrient concentrations of nine samples trees for each species. Then, the nutrient concentrations and resorption efficiency were compared, and the soil nutrients utilization strategies were further analyzed. Results: The results showed that the N concentration was significantly higher in the green and senesced leaves of deciduous trees than in the leaves of evergreen trees. The two life-form trees were both N limited and evergreen trees were more sensitive to N limitation. The NRE and PRE in the deciduous trees were significantly higher than those in the evergreen trees. The NRE was significantly positively correlated with the PRE in the deciduous trees. As the soil N and P concentrations increased, the nutrient resorption efficiency (NuRE) of the evergreen trees increased, but that of the deciduous trees decreased. Compared with the deciduous trees, the evergreen trees were more sensitive to the feedback of soil N and P concentrations. These findings reveal the N and P nutrient resorption mechanism of evergreen and deciduous trees and fill a gap in the understanding of nutrient resorption in urban ecosystems.

Correlation between ESR1 and APOE gene polymorphisms and risk of osteonecrosis of the femoral head: a case-control study.

BACKGROUND: Osteonecrosis of the femoral head (ONFH) is a disease with a high disability rate, and genetic factors are closely related to its pathogenesis. This study aimed to investigate the possible correlation between ESR1 and APOE gene polymorphisms and the risk of ONFH. METHODS: In this case-control study, the potential association between three genetic variants (rs2982573 C < T, rs10872678 C < T, and rs9322332 A < C) of the ESR1 gene and two genetic variants (rs7259620 A < G and rs769446 C < T) of the APOE gene with the risk of ONFH was investigated. Correlations between gene polymorphisms and ONFH risk were assessed using logistic regression analysis, with calculation of odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The overall analysis demonstrated that rs9322332 in the ESR1 gene exhibited a correlation with a decreased risk of ONFH under the homozygous (AA vs.CC: OR = 0.69, 95% CI [0.53-0.90], p = 0.006), dominant (CA + AA vs. CC: OR = 0.70, 95% CI [0.54-0.90], p = 0.006), and additive (OR = 0.79, 95% CI [0.66-0.95], p = 0.013) models. The stratification analysis revealed that rs9322332 was linked to a lower risk of ONFH in subgroups characterized by individuals aged over 51 years and non-smokers. Nevertheless, there were no notable correlations found between ESR1 rs2982573 and rs10872678, as well as APOE rs7259620 and rs769446, with the risk of ONFH. CONCLUSION: ESR1-rs9322332 is closely linked to a decreased risk of ONFH, thereby enhancing our understanding of the relationship between gene polymorphisms and ONFH.

Effect of OR51E1 single nucleotide polymorphisms on glioma susceptibility in the Chinese Han population.

BACKGROUND: Glioma is one of the common primary intracranial tumors, which is heterogeneous among individuals with a low cure rate. Our study aimed to investigate the association between single nucleotide polymorphisms (SNPs) of the OR51E1 gene and glioma susceptibility in the Chinese Han population. METHODS: A total of six SNPs on OR51E1 in 1,026 subjects (526 cases and 500 controls) were genotyped by MassARRAY iPLEX GOLD assay. The association between these SNPs and glioma susceptibility was analyzed using logistic regression, and odds ratios (ORs) and 95% confidence intervals (CIs) were also calculated. The multifactor dimensionality reduction (MDR) method was applied to detect "SNP-SNP" interactions. RESULTS: In the overall sample, polymorphisms rs10768148, rs7102992, and rs10500608 were identified to be associated with glioma risk. In the stratified analysis based on gender, only polymorphism rs10768148 was observed to be associated with the risk of glioma. In the age-stratified analysis, rs7102992, rs74052483, and rs10500609 contributed to the risk of glioma in subjects aged > 40 years. And polymorphisms rs10768148 and rs7102992 were associated with the risk of glioma in subjects aged ≤ 40 years and subjects with astrocytoma. In addition, a strong synergistic relationship between rs74052483 and rs10768148, and a strong redundant relationship between rs7102992 and rs10768148 were identified in the study. CONCLUSIONS: This study demonstrated the association of OR51E1 polymorphisms with glioma susceptibility, providing a basis for assessing glioma risk-associated variants in the Chinese Han population.

High-quality genome assembly and comparative genomic profiling of yellowhorn (Xanthoceras sorbifolia) revealed environmental adaptation footprints and seed oil contents variations.

Yellowhorn (Xanthoceras sorbifolia) is a species of deciduous tree that is native to Northern and Central China, including Loess Plateau. The yellowhorn tree is a hardy plant, tolerating a wide range of growing conditions, and is often grown for ornamental purposes in parks, gardens, and other landscaped areas. The seeds of yellowhorn are edible and contain rich oil and fatty acid contents, making it an ideal plant for oil production. However, the mechanism of its ability to adapt to extreme environments and the genetic basis of oil synthesis remains to be elucidated. In this study, we reported a high-quality and near gap-less yellowhorn genome assembly, containing the highest genome continuity with a contig N50 of 32.5 Mb. Comparative genomics analysis showed that 1,237 and 231 gene families under expansion and the yellowhorn-specific gene family NB-ARC were enriched in photosynthesis and root cap development, which may contribute to the environmental adaption and abiotic stress resistance of yellowhorn. A 3-ketoacyl-CoA thiolase (KAT) gene (Xso_LG02_00600) was identified under positive selection, which may be associated with variations of seed oil content among different yellowhorn cultivars. This study provided insights into environmental adaptation and seed oil content variations of yellowhorn to accelerate its genetic improvement.

Genetic polymorphisms in CYP2B6 may be associated with lung cancer risk in the Chinese Han population.

BACKGROUND: Our study aimed to elucidate the association between single nucleotide polymorphisms (SNPs) in CYP2B6 gene and susceptibility to lung cancer (LC). METHODS: Five SNPs in CYP2B6 were genotyped in Chinese Han population (507 cases and 505 controls) utilizing Agena MassARRAY. The relationship between these SNPs and LC susceptibility was assessed using odds ratios, 95% confidence intervals, and χ2 tests. Additionally, multifactor dimensionality reduction was employed to analyze SNP-SNP interactions. Bioinformatics methods were applied to investigate the function of these SNPs. RESULTS: We found that rs2099361 was associated with an increased susceptibility to LC in the codominant model (OR = 1.31, p = 0.045). Stratification analysis revealed the allele G at rs4803418 and the allele T at rs4803420 of CYP2B6 (BMI >24 kg/m2) were significantly linked to decreased susceptibility of LC. Conversely, the allele C at rs12979270 (BMI >24 kg/m2) showed increased susceptibility to LC. Moreover, a robust redundant relationship between rs12979270 and rs4803420 was identified in the study. According to the VannoPortal database, we found that rs4803420, rs12979270 and rs2099361 may modulate the binding affinity of LMNB1, SP1 and HDAC2, respectively. CONCLUSIONS: Our results suggest that SNPs in the CYP2B6 gene play crucial roles in LC susceptibility.

Combined transcriptome and proteome analysis revealed the molecular regulation mechanisms of zinc homeostasis and antioxidant machinery in tobacco in response to different zinc supplies.

Zinc (Zn) is an essential micronutrient for plants. Adequate regulation of Zn uptake, transport and distribution, and adaptation to Zn-deficiency stress or Zn-excess toxicity are crucial for plant growth and development. However, little has been done to understand the molecular responses of plants toward different Zn supply levels. In the present study, we investigated the growth and physiological responses of tobacco seedlings grown under Zn-completely deficient, Zn-limiting, Zn-normal, and Zn-4-fold sufficient conditions, respectively, and demonstrated that Zn deficiency/limitation caused oxidative stress and impaired growth of tobacco plants. Combined transcriptome and proteome analysis revealed up-regulation of genes/proteins associated with Zn uptake and distribution, including ZIPs, NAS3s, and HMA1s, and up-regulation of genes/proteins involved in regulation of oxidative stress, including SODs, APX1s, GPX6, and GSTs in tobacco seedlings in response to Zn deficiency/limitation, suggesting that tobacco possessed mechanisms to regulate Zn homeostasis primarily through up-regulation of the ZIPs-NAS3s module, and to alleviate Zn deficiency/limitation-induced oxidative stress through activation of the antioxidant machinery. Our results provide novel insights into the adaptive mechanisms of tobacco in response to different Zn supplies, and would lay a theoretical foundation for development of varieties of tobacco or its relatives with high tolerance to Zn-deficiency.