Identification of Pyroptosis-Related Genes Regulating the Progression of Chronic Rhinosinusitis with Nasal Polyps.

INTRODUCTION: Chronic rhinosinusitis with nasal polyps (CRSwNP) is an immunologic disease, and pyroptosis, an inflammation-based cellular death, strictly modulates CRSwNP pathology, whereas the pyroptosis genes and mechanisms involved in CRSwNP remain unclear. Herein, we explored disease biomarkers and potential therapeutic targets for pyroptosis and immune regulation in CRSwNP using bioinformatics analysis and tissue-based verification. METHODS: We retrieved the transcriptional profiles of the high-throughput dataset GSE136825 from the Gene Expression Omnibus database, as well as 170 pyroptosis-related gene expressions from GeneCards. Using R, we identified differentially expressed pyroptosis-related genes and examined the potential biological functions of the aforementioned genes using Gene Ontology, Kyoto Encyclopedia of the Genome pathway, immune infiltration, and protein-protein interaction (PPI) network analyses, thereby generating a list of hub genes. The hub genes were, in turn, verified using real-time quantitative polymerase chain reaction (qRT-PCR), immunohistochemistry (IHC), and Western blotting (WB). Ultimately, using the StarBase and miRTarBase databases, we estimated the targeting microRNAs and long chain non-coding RNAs. RESULTS: We demonstrated that the identified pyroptosis-related genes primarily modulated bacterial defense activities, as well as inflammasome immune response and assembly. Moreover, they were intricately linked to neutrophil and macrophage infiltration. Furthermore, we validated the tissue contents of hub genes AIM2, NLPR6, and CASP5 and examined potential associations with clinical variables. We also developed a competitive endogenous RNA (ceRNA) modulatory axis to examine possible underlying molecular mechanisms. CONCLUSION: We found AIM2, CASP5, and NLRP6, three hub genes for pyroptosis in chronic rhinosinusitis with nasal polyps, by biological analysis, experimental validation, and clinical variable validation.

Reduced Proliferative Capacity and Defense against Staphylococcus aureus in Human Nasal Mucosal Epithelium Lacking ZNF365.

INTRODUCTION: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common chronic inflammatory disease of the nose characterized by barrier disruption and environmental susceptibility, and the deletion of ZNF365 may be a factor inducing these manifestations. However, there is no study on the mechanism of action between CRSwNP and ZNF365. Therefore, this study focuses on the effect of the zinc finger protein ZNF365 on the proliferation of nasal mucosal epithelial cells and their defense against Staphylococcus aureus (S. aureus). METHODS: Immunohistochemistry and Western blot were applied to verify the changes of ZNF365 expression in nasal polyp tissues and control tissues, as well as in primary epithelial cells. ZNF365 was knocked down in human nasal mucosa epithelial cell line (HNEpc), and the proliferation, migration, and transdifferentiation of epithelium were observed by immunofluorescence, QPCR, CCK8, and cell scratch assay. The changes of mesenchymal markers and TLR4-MAPK-NF-κB pathway were also observed after the addition of S. aureus. RESULTS: ZNF365 expression was reduced in NP tissues and primary nasal mucosal epithelial cells compared to controls. Knockdown of ZNF365 in HNEpc resulted in decreased proliferation and migration ability of epithelial cells and abnormal epithelial differentiation (decreased expression of tight junction proteins). S. aureus stimulation further inhibited epithelial cell proliferation and migration, while elevated markers of epithelial-mesenchymal transition and inflammatory responses occurred. CONCLUSION: ZNF365 is instrumental in maintaining the proliferative capacity of nasal mucosal epithelial cells and defending against the invasion of S. aureus. The findings suggest that ZNF365 may participate in the development of CRSwNP.

Transcriptome Analysis of White- and Red-Fleshed Apple Fruits Uncovered Novel Genes Related to the Regulation of Anthocyanin Biosynthesis.

The red flesh coloration of apples is a result of a biochemical pathway involved in the biosynthesis of anthocyanins and anthocyanidins. Based on apple genome analysis, a high number of regulatory genes, mainly transcription factors such as MYB, which are components of regulatory complex MYB-bHLH-WD40, and several structural genes (PAL, 4CL, CHS, CHI, F3H, DFR, ANS, UFGT) involved in anthocyanin biosynthesis, have been identified. In this study, we investigated novel genes related to the red-flesh apple phenotype. These genes could be deemed molecular markers for the early selection of new apple cultivars. Based on a comparative transcriptome analysis of apples with different fruit-flesh coloration, we successfully identified and characterized ten potential genes from the plant hormone transduction pathway of auxin (GH3); cytokinins (B-ARR); gibberellins (DELLA); abscisic acid (SnRK2 and ABF); brassinosteroids (BRI1, BZR1 and TCH4); jasmonic acid (MYC2); and salicylic acid (NPR1). An analysis of expression profiles was performed in immature and ripe fruits of red-fleshed cultivars. We have uncovered genes mediating the regulation of abscisic acid, salicylic acid, cytokinin, and jasmonic acid signaling and described their role in anthocyanin biosynthesis, accumulation, and degradation. The presented results underline the relationship between genes from the hormone signal transduction pathway and UFGT genes, which are directly responsible for anthocyanin color transformation as well as anthocyanin accumulation during apple-fruit ripening.

Multimolecular characteristics and role of BRCA1 interacting protein C-terminal helicase 1 (BRIP1) in human tumors: a pan-cancer analysis.

BACKGROUND: The aberrant expression of BRIP1 was associated with several cancers; however, the panoramic picture of BRIP1 in human tumors remains unclear. This study aims to explore the pan-cancerous picture of the expression of BRIP1 across 33 human cancers. METHODS: Based on the data from TCGA and GTEx, a series of bioinformatic analyses were applied to systematically explore the genetic landscape and biologic function of BRIP1 in 33 human tumors. RESULTS: We observed prognosis-related differential BRIP1 expressions between various carcinomas and the corresponding normal tissues. "Basal transcription factors," "homologous recombination," "nucleotide excision repair," and DNA metabolism pathways may play a role in the functional mechanisms of BRIP1. Patients with uterine corpus endometrial carcinoma presented with the highest alteration frequency of BRIP1 (nearly 10%). Single-nucleotide and copy number variations of BRIP1 were noticed in multiple cancers, and the expression of BRIP1 is significantly regulated by copy number variation in breast invasive carcinoma and lung squamous cell carcinoma. BRIP1 expression is negatively correlated with the DNA methylation levels in many tumors and is associated with the activation of apoptosis, cell cycle, DNA damage response, and inhibition of hormone ER and RNS/MARK signaling pathways. Moreover, a positive correlation was observed between BRIP1 expression and the immune infiltration levels of cancer-associated fibroblasts and CD8+ T cells in lung adenocarcinoma. CONCLUSION: Our pan-cancer analysis of BRIP1 provides a valuable resource for understanding the multimolecular characteristics and biological function of BRIP1 across human cancers.

Two Novel α-Thalassemia Mutations CD 39 -C [Thr > Pro] and CD 109 ACC > CCC [Thr > Pro] Identified in Two Chinese Families: A Case Report.

We reported the identification of two rare α-thalassemia silent carriers with novel HBA1 mutations of CD 39 -C [Thr > Pro] (HBA1: c.114del; p.Thr39Profs*11) and CD 109 ACC > CCC [Thr > Pro] (HBA1: c.325A > C; p. Thr109Pro), respectively. The two probands were pregnant women diagnosed with mild hypochromic anemia or microcytic hypochromic anemia by routine blood tests. They started iron therapy before taking differential diagnosis from iron deficiency anemia. After wait and watch approach, they both accepted thalassemia genetic screening, which identified CD 39 -C [Thr > Pro] and CD 109 ACC > CCC [Thr > Pro], respectively. Due to inappropriate iron therapy, worse anemia and iron overload were noticed in the first proband, but no obvious side effect was found in both probands. Functional analysis showed that, relative to the wild type, CD 39 -C [Thr > Pro] considerably reduced the expression of the HBA1 protein while CD 109 ACC > CCC [Thr > Pro] only had a minor impact. Our study highlighted the importance of gestational thalassemia screening based on next-generation sequencing for identifying novel rare thalassemia variants and increased our understanding about the relationship between genotype and phenotype of α-thalassemia.

The Role of Tumor Microenvironment in Regulating the Plasticity of Osteosarcoma Cells.

Osteosarcoma (OS) is a malignancy that is becoming increasingly common in adolescents. OS stem cells (OSCs) form a dynamic subset of OS cells that are responsible for malignant progression and chemoradiotherapy resistance. The unique properties of OSCs, including self-renewal, multilineage differentiation and metastatic potential, 149 depend closely on their tumor microenvironment. In recent years, the likelihood of its dynamic plasticity has been extensively studied. Importantly, the tumor microenvironment appears to act as the main regulatory component of OS cell plasticity. For these reasons aforementioned, novel strategies for OS treatment focusing on modulating OS cell plasticity and the possibility of modulating the composition of the tumor microenvironment are currently being explored. In this paper, we review recent studies describing the phenomenon of OSCs and factors known to influence phenotypic plasticity. The microenvironment, which can regulate OSC plasticity, has great potential for clinical exploitation and provides different perspectives for drug and treatment design for OS.

[Analysis of SEDL gene mutation in a Chinese pedigree with X-linked spondyloepiphyseal dysplasia tarda].

OBJECTIVE: To explore the molecular mechanism for a family with hereditary X-linked spondyloepiphysealdysplasia tarda (SEDT). METHODS: For 3 affected males and 2 obligate carrier females from the family, exons 3 to 6 of SEDL gene were amplified with PCR and sequenced. RESULTS: In the three patients, a deletional mutation (c.267_271delAAGAC) in exon 5 has been identified, which has caused frameshift of the protein product. CONCLUSION: c.267_271delAAGAC frameshift mutation of the exon 5 of the SEDL gene probably underlies the disease in this family.

Increased FGF2 expression promotes immune cell infiltration and correlates with an unfavorable prognosis in thyroid cancer.

To delve into the expression and functions of FGF2 in patient with thyroid cancer (THCA), we conducted a systematic analysis of the association of FGF2 with immune cell infiltration, and prognosis in THCA patients. The transcription and protein levels, methylation, and biological properties of FGF2 were examined, along with its correlation with prognosis and immune cell infiltration in THCA patients using online databases UALCAN, Human Protein Atlas, Kaplan-Meier Plotter, DNMIVD, cBioPortal, GEPIA, Metascape, Linkedomics and TIMER. Clinical samples were collected for Western blot analyses. FGF2 was substantially overexpressed in the tumor group and shown correlations with age, tumor histology, nodal metastasis, and cancer stages. Moreover, higher expression of FGF2 (HR = 3.42, 95 % CI:1.57-7.44, p = 0.00099) was greatly correlated with poorer relapse-free survival in THCA patients, particularly in female patients. FGF2 methylation level was increased in the tumor group (p = 1.29E-6), and higher methylation levels of FGF2 were positively correlated with the poorer progression-free interval in THCA patients (p = 0.015). FGF2 mutations were markedly associated with shorter disease-free survival, with a mutation rate of 6 % among the total 498 THCA patients. FGF2 functions were potentially related to cell adhesion, cytokine-cytokine receptor interaction and angiogenesis. FGF2 expression showed positive correlations with the infiltration of B cells (Cor = 0.569, p = 1.04e-42), CD4+ T cells (Cor = 0.555, p = 9.43e-41), macrophages (Cor = 0.438, p = 2.94e-42), neutrophils (Cor = 0.578, p = 9.354e-45), and dendritic cells (Cor = 0.591, p = 5.00e-47). FGF2 is a potential prognostic marker in THCA patients, with its functions possibly related to cell adhesion, interaction of the cytokine-cytokine receptor, angiogenesis, and the promotion of multiple immune cell infiltration.

A DEA game cross-efficiency based improved method for measuring urban carbon emission efficiency in China.

An accurate evaluation of carbon emission efficiency (CEE) at the city level can provide guidelines for understanding low carbon performance, which is crucial to achieving dual carbon targets. Existing CEE studies focused on national, industrial, and provincial scales while neglecting the city level and failing to consider competing relationships among decision-making units in their measurement models. To fill these gaps, this paper introduces the data envelopment analysis game cross-efficiency model (DEA-GCE) to measure urban CEE performance and compares it with the traditional Super-SBM model using the data from 283 Chinese cities between 2006 and 2019. The results show that (1) the DEA-GCE method provided more intensive and stable results. (2) Overall CEE of Chinese cities declined slightly amidst fluctuations during this period. (3) CEE in cities exhibits spatial clustering characteristics. CEE performance in Northeast China has improved, while CEE in Northwest China continues to lag behind. This study introduced an innovative method for calculating urban CEE and conducted an empirical study of 283 Chinese cities, which has implications for formulation of emission reduction policies.

Atmospheric wet and dry phosphorus deposition in Lake Erhai, China.

Lake Erhai is a potentially phosphorus (P)-limited lake and its water quality may have been affected by atmospheric P deposition. However, there have been few studies on atmospheric P deposition in this lake. In this study, we established five wet deposition monitoring sites and two dry deposition monitoring sites around Lake Erhai to quantify the wet and dry deposition of total phosphorus (TP), including dissolved inorganic phosphorus (DIP), dissolved organic phosphorus (DOP) and particulate phosphorus (PP) from July 2022 to June 2023. Wet deposition fluxes of P species were collected by automatic rainfall collection instrument, and dry deposition fluxes were estimated using airborne concentration measurements and inferential models. The results reveal that among the different P components, DOP had the highest contribution (50%) to wet TP deposition (average all sites 12.7 ± 0.7 mg P m2/yr), followed by PP (40%) and DIP (10%). Similarly, DOP (51%) was the major contributor to dry TP deposition (average two sites 2.4 ± 0.9 mg P m2/yr), followed by DIP (35%) and PP (14%). Wet deposition dominated the annual total TP deposition (wet plus dry), accounting for approximately 83%. The key seasons for dry deposition were spring and autumn, which accounted for 64% of the annual total dry TP deposition. In comparison, wet deposition was significantly higher in the summer, accounting for 73% of the annual total wet TP deposition. The results of the potential source contribution function and concentration-weighted trajectories analysis indicate that local source emission and long-range transport from surrounding cities jointly exerted a substantial influence on aerosol P concentrations, particularly in the eastern and northwestern regions of the lake. These findings provide a comprehensive understanding of the different P components in atmospheric deposition, which is beneficial for developing effective strategies to manage the P cycle in Lake Erhai.

Mutation identification of the DSPP in a Chinese family with DGI-II and an up-to-date bioinformatic analysis.

In this study, through linkage analysis of a four-generation Chinese family with multiple members afflicted with DGI (type II), we identified a novel missense mutation in DSPP. The mutation was located in exon 2 at the second nucleotide position of the last codon and resulted in a substitution of a proline with a leucine residue (c.50C>T, p.P17L, g.50C>T). To assess the potential effects of this novel mutation, we utilized various bioinformatics analysis programs. The results indicate that the mutation likely affects protein cleavage/trafficking. We also analyzed previously reported mutations of DSPP. In summary, our finding supports that the genomic sequence that corresponds to the P17 residue of DSPP is a mutational hotspot and P17 may be critical for the function of DSPP.

Exploring the effect of human capital on carbon emissions: evidences from 125 countries.

Human capital (HC) plays a crucial role in economic growth, and also has a considerable effect on environmental performance, including carbon emissions (CEs). Existing studies have drawn inconsistent conclusions on whether and how HC affects CEs, and most of them conduct case studies of a certain country or several countries with similar economic backgrounds. In order to accurately determine the effect and the influence mechanism of HC on CEs, this research conducted an empirical study by applying econometric method and the panel data of 125 countries over the period 2000-2019. The empirical results indicate that there is an inverted U-shaped nexus between HC and CEs of full sample countries, revealing that HC will increase CEs before turning point and decrease CEs after turning point. From a heterogeneity perspective, this inverted U-shaped nexus only exists in high and upper-middle income countries, while is not supported in low and lower-middle income countries. This study further disclosed that HC can affect CEs by the mediating effects of labor productivity, energy intensity, and industrial structure from a macro perspective. Specifically, HC will increase CEs by promoting labor productivity, while decrease CEs by reducing energy intensity and the proportion of secondary industry. These results can provide important references for governments of different countries to make tailored carbon reduction policies according to the mitigation effect of HC on CEs.

A Effectiveness-and Efficiency-Based Improved Approach for Measuring Ecological Well-Being Performance in China.

Finding solutions to the challenges posed by China's urbanization is an urgent, pressing global concern. An effective approach for evaluating the ecological well-being performance (EWP) is a guideline for improvement. Most previous studies have focused on the evaluation of EWP efficiency without considering the effectiveness of the EWP, which may mislead the practice of improving the EWP. This paper proposed a bi-dimensional effectiveness and efficiency perspective evaluation of the EWP for pursuing sustainable development goals. The Ecological Consumption Index and the Human Development Index are selected to evaluate indicators for the EWP. The entropy method, line-weighted method, and four-quadrant evaluation framework are used to disclose EWP effectiveness. A Super SBM model and the DEA moving split-windows analysis method are applied to calculate the EWP efficiency. Data from 30 provinces in China for the period of 1997 to 2019 have been collected for empirical study to demonstrate the effectiveness of the proposed method. The main findings of the case study are: (1) The ECI and HDI increased during the study period, while the annual average value of the EWP efficiency among 30 provinces in China has decreased with fluctuation; (2) provinces in southern China and Chongqing have a low level of ECI and demonstrate good performance in the HDI; and (3) most developed regions, such as Beijing, Shanghai, and Guangdong, have not presented the best EWPs. The results of this study can provide a basis for understanding the EWP in China so as to formulate targeted sustainable-development strategies.

Bioinformatics analysis of CUL2/4A/9 and its function in head and neck squamous cell carcinoma.

INTRODUCTION: Several previous studies have shown that differential expression of cullin (CUL) family proteins may be involved in mediation of the signal transduction pathways associated with cancer. However, the function of CULs is still unclear in head and neck squamous cell carcinoma (HNSCC). MATERIAL AND METHODS: We used The Cancer Genome Atlas (TCGA) database, cBioPortal, Metascape, STRING, Cytoscape, Tumor Immune Estimation Resource (TIMER), Kaplan-Meier plotter, and Tumor Immune System Interaction Database (TISIDB) to access the expression of CULs and the possible correlation with the tumourigenesis, development, prognosis, immunity, and transcriptional level of CULs in HNSCC. Furthermore, real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect messenger ribonucleid acid (mRNA) levels in HNSCC tissues and cell samples. We also explored the cell proliferation and migration separately by CCK8 assay and wound healing assay. RESULTS: The results showed that the expressions of CUL2/4A were upregulated and CUL9 was downregulated in HNSCC patients as compared with normal patients. CUL2/4A/9 were also linked to the clinicopathological features and overall survival of HNSCC in bioinformatics analysis. Moreover, we noticed that CUL2/4A/9 may take part in tumour-specific immune response by modulating the tumour-infiltrating lymphocytes (TILs) and immunomodulators. Lastly, we found that CUL2/4A/9 could promote cellular proliferation and migration. CONCLUSION: These results suggest that the transcriptional levels of CUL2/4A/9 were upregulated and these genes could affect proliferation and migration of HNSCC cells. Therefore, CUL2/4A/9 could potentially function as novel independent biomarkers in HNSCC patients.

Identification of SLC2A3 as a prognostic indicator correlated with the NF-κB/EMT axis and immune response in head and neck squamous cell carcinoma.

SLC2A3 is an important member of the glucose transporter superfamily. It has been recently suggested that upregulation of SLC2A3 is associated with poor survival and acts as a prognostic marker in a variety of tumors. Unfortunately, the prognostic role of SLC2A3 in head and neck squamous cell carcinoma (HNSC) is less known. In the present study, we analyzed SLC2A3 expression in HNSC and its correlation with prognosis using TCGA and GEO databases. The results showed that SLC2A3 mRNA expression was higher in HNSC compared with adjacent normal tissues, which was validated with our 9 pairs of HNSC specimens. Moreover, high SLC2A3 expression predicted poor prognosis in HNSC patients. Mechanistically, GSEA revealed that high expression of SLC2A3 was enriched in epithelial-mesenchymal transition (EMT) and NF-κB signaling. In HNSC cell lines, SLC2A3 knockdown inhibited cell proliferation and migration. In addition, NF-κB P65 and EMT-related gene expression was suppressed upon SLC2A3 knockdown, indicating that SLC2A3 may play a preeminent role in the progression of HNSC through the NF-κB/EMT axis. Meanwhile, the expression of SLC2A3 was negatively correlated with immune cells, suggesting that SLC2A3 may be involved in the immune response in HNSC. The correlation between SLC2A3 expression and drug sensitivity was further assessed. In conclusion, our study demonstrated that SLC2A3 could predict the prognosis of HNSC patients and mediate the progression of HNSC via the NF-κB/EMT axis and immune responses.

Evaluation Method for Urban Public Service Carrying Capacity (UPSCC): A Qualitative-Quantitative Bi-Dimensional Perspective.

Urban Public Service Carrying Capacity plays an essential role in urban social and economic development. However, existing study has been focused on the evaluation of UPSCC from a quantitative perspective. It is necessary to evaluate UPSCC from a qualitative-quantitative bi-dimensional perspective. This paper establishes an innovative evaluation method for UPSCC based on a qualitative-quantitative bi-dimensional (QQBD) perspective. The proposed QQBD-based UPSCC evaluation method can help identify the weak areas of public services. The conclusions of this study are as follows. Firstly, public services are people-oriented social resources, which should be evaluated from both quantitative and qualitative perspectives. Secondly, the quantitative measurement of public service carrying capacity needs to consider both UPSCC load and carrier, while the qualitative measurement needs to consider the satisfaction among stakeholders. Thirdly, the demonstration of the case study cities shows the effectiveness of the qualitative-quantitative bi-dimensional UPSCC evaluation method. By applying the QQBD-based UPSCC evaluation method introduced in this study, decision makers can identify the specific areas that affect the UPSCC performance, and thus tailor-made policy can be designed for improving UPSCC performance by adjusting UPSCC quantity and quality.

[Analysis of metabolite differences in skin between Clapp's Favorite and its mutant Red Clapp's Favorite through non-targeted metabolomics].

Red Clapp's Favorite is the red mutation cultivar of the pear cultivar Clapp's Favorite. Fruit color is an important feature of pear fruits, with red skin generally attracting consumers. Anthocyanin, chlorophyll, and carotenoids are the most important pigments in the color formation of fruits. The red color of pear skin is mainly due to the concentration and composition of anthocyanin. Metabolomics is an emerging discipline that focuses on the qualitative and quantitative analysis of small metabolites with low molecular weight in biological cells and tissues. As an important part of systems biology, it is an effective means to solve many complex biological problems. Studies have analyzed pigment content, composition, and differentially expressed genes in the skin of green and red pears from various aspects. Anthocyanins are responsible for physiological activity on regulating pathways. The aim of this study was to discover differential metabolites in the skin of Clapp's Favorite and its red mutation cultivar Red Clapp's Favorite. The metabolic components were detected using high-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS). Chromatographic experiments were performed on an HSS T3 column (100 mm×2.1 mm, 1.8 µm) by using a mobile phase consisting of 0.1% (v/v) formic acid in acetonitrile and water, and mass spectrometry was conducted in the positive and negative modes by electrospray ionization (ESI). Red Clapp's Favorite and Clapp's Favorite were collected from the pear germplasm resource nursery of Yantai Institute of Agricultural Sciences in Shandong. The data were analyzed by principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) as well as cluster analysis and heat map. The first two principal components exhibited 62.3% and 8% of the total variance in the positive and negative ion modes, respectively. PCA can generally reflect metabolite differences between the two groups of samples, and there are significant differences in metabolites between the two cultivars. The results showed that PLS-DA clearly distinguishes the two groups of samples, which can be used to analyze the subsequent difference in components. The compounds were identified based on data retrieved from the PMDB databases according to the accurate mass number, secondary fragment, and isotope distribution. The results showed that the metabolite content in the skin of Red Clapp's Favorite and Clapp's Favorite were significant. There were 83 different metabolites (P<0.05, variable importance in project (VIP)≥1), including phenols and amino acids, which are involved in flavonoid metabolism, amino acid metabolism, phenyl propanoid biosynthesis, and other metabolic pathways, including 5 polyphenols, 3 flavonoids, 1 amino acid and derivatives, 8 phenylpropanes, 2 anthocyanins, 5 proanthocyanidins, 6 flavanols, 14 flavonols, 2 isoflavones, 13 triterpenoids, 3 organic acids and derivatives, 1 vitamin, 3 organic acids and derivatives, 15 lipids, and 2 other compounds. The chlorogenic acid and crypto-chlorogenic acid in Red Clapp's Favorite are 2.40 and 3.46 times as much as those in Clapp's Favorite. The anthocyanins of cornulin 3-glucoside and cornulin 3-galactoside were 10.235 and 9.394 times, respectively. Phenolic epicatechin and catechin increased by 4.689 and 4.635, respectively. The content of phenylpropane 3, 4-dihydroxycinnamic acid in Red Clapp's Favorite increased by 3.13 times. Among the 83 differential metabolites, 23 metabolites were enriched in the pathway. To display the relationship between the samples and the differences in metabolites among the different samples intuitively, hierarchical clustering and heat map analysis were performed on the metabolite expression levels with significant differences in the enrichment pathways. The Kyoto Encyclopedia of Genes and Genomes database was used to further analyze the pathway enrichment of different metabolites. According to the results, there were 6 metabolic pathways (P<0.05): flavonoid biosynthesis, flavone and flavonol biosynthesis, phenylpropanoid biosynthesis, butanoate metabolism, phenylalanine metabolism, and tyrosine metabolism. Plant secondary metabolism shows a complex diversity. This study would screen out other pathways affecting the biosynthesis of flavonoids, which could provide reference for the further study of biosynthesis and biological function of flavonoids in red fruits. This study provides a useful reference for metabolomics of red pears, which could provide a theoretical reference for the quality analysis and biological function research of pears.

Evaluating the Environmental Impact of Construction within the Industrialized Building Process: A Monetization and Building Information Modelling Approach.

Industrialization has been widely regarded as a sustainable construction method in terms of its environmental friendliness. However, existing studies mainly consider the single impact of greenhouse gas emissions or material consumption in the construction process of industrialized buildings, and pay less attention to ecological pollution and community interest, which leads to an insufficient understanding. There is an urgent need to systematically carry out accurate assessment of comprehensive construction environmental impact within industrialized building processes. Various methods, including face-to-face interviews, field research and building information modeling (BIM), were used for data collection. Four categories selected for the study included resource consumption, material loss, ecological pollution, and community interest. A life cycle assessment (LCA) model, namely input-process-output model (IPO), is proposed to analyze the construction environmental impact of the standard layer of industrialized buildings from four life cycle stages, namely, transportation, stacking, assembly and cast-in-place. The monetization approach of willingness to pay (WTP) was applied to make a quantitative comparison. Results reveal that the assembly stage has the largest impact on the environment at 66.13% among the four life cycle stages, followed by transportation at 16.39%, stacking at 10.29%, and cast-in-place at 7.19%. The key factors include power consumption, noise pollution, material loss, fuel consumption and component loss, which altogether account for more than 85% of the total impact. Relevant stakeholders can conduct their project using the same approach to determine the construction environmental performance and hence introduce appropriate measures to mitigate the environmental burden.

The assessment of epigenetic diversity, differentiation, and structure in the 'Fuji' mutation line implicates roles of epigenetic modification in the occurrence of different mutant groups as well as spontaneous mutants.

The 'Fuji' line includes many varieties with a similar genetic background and consistent inducement factors with epigenetic occurrence, thus it may be considered an ideal candidate for epigenetic research. In this study, 91 bud mutations of 'Fuji' apple were used as the test materials. Using the genetic variation within 'Fuji' as the control, the characteristics of epigenetic variation at different levels in both varieties and mutant groups were examined. The results showed that: (1) the global genomic DNA methylation level of the 91 bud mutants of 'Fuji' ranged from 29.120%-45.084%, with an average of 35.910%. Internal cytosine methylation was the main DNA methylation pattern. Regarding the variation of methylation patterns of 'Fuji' mutants, the vast majority of loci maintained the original methylation pattern existed in 'Fuji'. CHG methylation variation was the main type of variation; (2) the variation in methylation patterns between the mutant groups was greater than that of methylation levels. Among these patterns, the variation in CHG methylation patterns (including CHG hypermethylation and CHG demethylation) was expected to be dominant. The observed variation in methylation levels was more important in the Color mutant group; however, the variation in methylation patterns was more obvious in both the early maturation and Spur mutant groups. Moreover, the range of variation in the Early-maturation group was much wider than that in the Spur mutant group; (3) epigenetic diversity and genetic diversity were both low between the mutant groups. In the 'Fuji' mutant groups, there was few correlation between genetic and epigenetic variation, and epigenetic differentiation resulted in more loci with moderate or greater differentiation; (4) the purifying selection seemed to play a major role in the differentiation of different groups of 'Fuji' mutants (65.618%), but epigenetic diversity selection still occurred at nearly 35% of loci. Sixteen epigenetic outlier loci were detected.

Screening of mitochondrial tRNA mutations in 300 infants with hearing loss.

Mitochondrial DNA (MtDNA) mutations are the important causes for hearing loss. To see the contribution of mtDNA to deafness, we screened for mutations in mt-tRNA genes from 300 deaf infants and 200 healthy subjects. Moreover, we analyzed the mtDNA copy number and ROS levels in patients carrying the mt-tRNA mutations. Consequently, 3 mt-tRNA mutations: tRNALeu(UUR) A3243G; tRNAAla T5655C and tRNAGlu A14692G were identified, however, these mutations were not detected in controls. Of these, the A3243G mutation created a novel base-pairing (13G-23A) in the D-stem of tRNALeu(UUR); while the T5655C mutation occurred at the very conserved acceptor arm of tRNAAla; in addition, the A14692G mutation was located at position 55 in the TΨC loop of tRNAGlu. Molecular analysis showed that patients harbouring the A3243G, T5655C and A14692G mutations had a lower level of mtDNA copy number, while ROS level increased significantly when compared with controls. Through the application of the pathogenicity scoring system, we noticed that the A3243G, T5655C and A14692G should be regarded as 'definitely pathogenic' mutations associated with deafness. Thus, our study provided novel insight into the pathophysiology, early detection of mitochondrial deafness.