Identification of ferroptosis-related genes in the progress of NASH

BackgroundNon-alcoholic steatohepatitis (NASH) is becoming more widespread, and some similarities exist between its etiology and ferroptosis. However, there are limited investigations on which ferroptosis-related genes (FRGs) are regulated in NASH and how to regulate them. We screened and validated the pivotal genes linked to ferroptosis in NASH to comprehend the function of ferroptosis in the development of NASH.MethodsTwo mRNA expression data were obtained from the Gene Expression Omnibus (GEO) as the training set and validation set respectively. FRGs were downloaded from FerrDb. The candidate genes were obtained from the intersection between differentially expressed genes (DEGs) and FRGs, and further analyzed using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The hub genes were identified by the protein-protein interaction (PPI) network and Cytoscape. Then, FRGs closely related to the severity of NASH were identified and further confirmed using the validation set and mouse models. Ultimately, based on these genes, a diagnostic model was established to differentiate NASH from normal tissues using another data set from GEO.ResultsA total of 327 FRGs in NASH were acquired and subjected to GSEA. And 42 candidate genes were attained by overlapping the 585 FRGs with 2823 DEGs, and enrichment analysis revealed that these genes were primarily engaged in the fatty acid metabolic, inflammatory response, and oxidative stress. A total of 10 hub genes (PTGS2、IL1B、IL6、NQO1、ZFP36、SIRT1、ATF3、CDKN1A、EGR1、NOX4) were then screened by PPI network. The association between the expression of 10 hub genes and the progress of NASH was subsequently evaluated by a training set and verified by a validation set and mouse models. CDKN1A was up-regulated along with the development of NASH while SIRT1 was negatively correlated with the course of the disease. And the diagnostic model based on CDKN1A and SIRT1 successfully distinguished NASH from normal samples.ConclusionIn summary, our findings provide a new approach for the diagnosis, prognosis, and treatment of NASH based on FRGs, while advancing our understanding of ferroptosis in NASH

Small and mighty: adaptation of superphylum Patescibacteria to groundwater environment drives their genome simplicity.

BackgroundThe newly defined superphylum Patescibacteria such as Parcubacteria (OD1) and Microgenomates (OP11) has been found to be prevalent in groundwater, sediment, lake, and other aquifer environments. Recently increasing attention has been paid to this diverse superphylum including > 20 candidate phyla (a large part of the candidate phylum radiation, CPR) because it refreshed our view of the tree of life. However, adaptive traits contributing to its prevalence are still not well known.ResultsHere, we investigated the genomic features and metabolic pathways of Patescibacteria in groundwater through genome-resolved metagenomics analysis of > 600 Gbp sequence data. We observed that, while the members of Patescibacteria have reduced genomes (~ 1 Mbp) exclusively, functions essential to growth and reproduction such as genetic information processing were retained. Surprisingly, they have sharply reduced redundant and nonessential functions, including specific metabolic activities and stress response systems. The Patescibacteria have ultra-small cells and simplified membrane structures, including flagellar assembly, transporters, and two-component systems. Despite the lack of CRISPR viral defense, the bacteria may evade predation through deletion of common membrane phage receptors and other alternative strategies, which may explain the low representation of prophage proteins in their genomes and lack of CRISPR. By establishing the linkages between bacterial features and the groundwater environmental conditions, our results provide important insights into the functions and evolution of this CPR group.ConclusionsWe found that Patescibacteria has streamlined many functions while acquiring advantages such as avoiding phage invasion, to adapt to the groundwater environment. The unique features of small genome size, ultra-small cell size, and lacking CRISPR of this large lineage are bringing new understandings on life of Bacteria. Our results provide important insights into the mechanisms for adaptation of the superphylum in the groundwater environments, and demonstrate a case where less is more, and small is mighty

New insights into β-glucan-enhanced immunity in largemouth bass Micropterus salmoides by transcriptome and intestinal microbial composition

β-glucan is widely used in aquaculture due to its immunostimulatory effects, but the specific effect and potential regulatory mechanism on largemouth bass (Micropterus salmoides) are still unclear. Here, we evaluated the effects of β-glucan on growth, resistance to Aeromonas schubertii, intestinal health, and transcriptome of largemouth bass to reveal the potential regulators, metabolic pathways, and altered differential microbiota. Four experimental diets were designed with β-glucan supplementation levels of 0 (control), 100 (LA-100), 200 (MA-200), and 300 (HA-300) mg kg-1, and each diet was fed to largemouth bass (79.30 ± 0.50 g) in triplicate for 70 days, followed by a 3-day challenge experiment. Results showed that different β-glucan supplementations had no significant effects on growth performance and whole-body composition. Fish fed a diet with 300 mg kg-1 β-glucan significantly increased the activity of lysozyme than those fed diets with 0 and 100 mg kg-1 β-glucan. In addition, the survival rate of largemouth bass in β-glucan supplementation groups was significantly higher than the control group at 12- and 24-h challenge by Aeromonas schubertii. Transcriptome analysis showed that a total of 1,245 genes were differentially expressed [|log2(fold change)| ≥1, q-value ≤0.05], including 109 immune-related differentially expressed genes (DEGs). Further analysis revealed that significantly upregulated and downregulated DEGs associated with immunity were mapped into 12 and 24 pathways, respectively. Results of intestinal microflora indicated that fish fed a diet with 300 mg kg-1 β-glucan had higher bacterial richness and diversity as evaluated by Sobs, Chao, Ace, and Simpson indices, but no significant differences were found in the comparison groups. Furthermore, 300 mg kg-1 β-glucan significantly increased the relative abundance of Mycoplasma and decreased Proteobacteria (mainly Escherichia-Shigella and Escherichia coli) and Bacillus anthracis in largemouth bass intestinal microflora. The findings of this study provided new insights that will be valuable in future studies to elucidate the mechanism of immunity enhancement by β-glucan

Climate warming accelerates temporal scaling of grassland soil microbial biodiversity.

Determining the temporal scaling of biodiversity, typically described as species-time relationships (STRs), in the face of global climate change is a central issue in ecology because it is fundamental to biodiversity preservation and ecosystem management. However, whether and how climate change affects microbial STRs remains unclear, mainly due to the scarcity of long-term experimental data. Here, we examine the STRs and phylogenetic-time relationships (PTRs) of soil bacteria and fungi in a long-term multifactorial global change experiment with warming (+3 °C), half precipitation (-50%), double precipitation (+100%) and clipping (annual plant biomass removal). Soil bacteria and fungi all exhibited strong STRs and PTRs across the 12 experimental conditions. Strikingly, warming accelerated the bacterial and fungal STR and PTR exponents (that is, the w values), yielding significantly (P < 0.001) higher temporal scaling rates. While the STRs and PTRs were significantly shifted by altered precipitation, clipping and their combinations, warming played the predominant role. In addition, comparison with the previous literature revealed that soil bacteria and fungi had considerably higher overall temporal scaling rates (w = 0.39-0.64) than those of plants and animals (w = 0.21-0.38). Our results on warming-enhanced temporal scaling of microbial biodiversity suggest that the strategies of soil biodiversity preservation and ecosystem management may need to be adjusted in a warmer world

Cancer risk from gaseous carbonyl compounds in indoor environment generated from household coal combustion in Xuanwei, China

Airborne carbonyls were characterized from emitted indoor coal combustion. Samples were collected in Xuanwei (Yunnan Province), a region in China with a high rate of lung cancer. Eleven of 19 types of samples (58%) demonstrated formaldehyde concentrations higher than the World Health Organization exposure limit (a 30-min average of 100 μg m−3). Different positive significant correlations between glyoxal/methylglyoxal and formaldehyde/acetaldehyde concentrations were observed, suggesting possible different characteristics in emissions between two pairs of carbonyl compounds. A sample in the highest inhalation risk shows 29.2 times higher risk than the lowest sample, suggesting different coal sampling locations could contribute to the variation of inhalation risk. Inhabitants in Xuanwei also tend to spend more time cooking and more days per year indoors than the national average. The calculated cancer risk ranged from 2.2–63 × 10−5, which shows 13 types of samples at high-risk level. Cumulative effect in combination with different carbonyls could have contributed to the additive actual inhalation cancer risk. There is a need to explicitly address the health effects of environmentally relevant doses, considering life-long exposure in indoor dwellings

Global diversity and biogeography of bacterial communities in wastewater treatment plants

Microorganisms in wastewater treatment plants (WWTPs) are essential for water purification to protect public and environmental health. However, the diversity of microorganisms and the factors that control it are poorly understood. Using a systematic global-sampling effort, we analysed the 16S ribosomal RNA gene sequences from ~1,200 activated sludge samples taken from 269 WWTPs in 23 countries on 6 continents. Our analyses revealed that the global activated sludge bacterial communities contain ~1 billion bacterial phylotypes with a Poisson lognormal diversity distribution. Despite this high diversity, activated sludge has a small, global core bacterial community (n = 28 operational taxonomic units) that is strongly linked to activated sludge performance. Meta-analyses with global datasets associate the activated sludge microbiomes most closely to freshwater populations. In contrast to macroorganism diversity, activated sludge bacterial communities show no latitudinal gradient. Furthermore, their spatial turnover is scale-dependent and appears to be largely driven by stochastic processes (dispersal and drift), although deterministic factors (temperature and organic input) are also important. Our findings enhance our mechanistic understanding of the global diversity and biogeography of activated sludge bacterial communities within a theoretical ecology framework and have important implications for microbial ecology and wastewater treatment processes

[[alternative]]Latent class analysis on preventive health service utilization among post-menopausal women in Taiwan

[[abstract]]停經是女性生命歷程之重要事件，停經之後對女性的影響包含生理與心理兩層面，已有越來越多的研究指出，婦女在經歷停經時所導致之生理/心理影響，具有顯著之隨機效應(random effect)，亦即每位婦女之主觀感受、症狀困擾、症狀嚴重度、因應策略等面向有相當大的個體差異，進而有不同反應之醫療服務利用。然而，除導因於心理層面、個別體質與營養的差異外，如何透過系統性的比較探索停經前後各項健康服務使用之高低次族群，以瞭解此部分群聚的分佈情況，進一步再分析其社會經濟與個人罹病史之相互關聯結構，將有助於釐清停經對於婦女影響之個別群體差異性，以及聯結其反應於各項健康服務使用之情況。本研究以2009年國家衛生研究院『國民健康訪問調查』為分析基礎，透過潛在類別資料分析法，提出下列七點結論：一、總體來說，停經後婦女相較於停經前有2至3倍的醫療服務使用(包括門、急診以及住院)。二、在健檢服務使用方面，總體來說停經後婦女相較於停經前有較高的健檢服務使用，但停經前有較高之子宮頸抹片、非政府補助之成人健檢及網路健康資訊使用。三、停經前婦女之健康服務使用可區分為高健檢服務使用組以及低健檢服務使用組，其中低健檢服務使用組占有60%。四、停經前婦女屬於低健檢組之特質包括: 年輕者、未婚者、低教育程度、居住於非北部地區、非與配偶同住者、抽菸/嚼檳榔/無規律運動習慣者、不具慢性病個人病史以及無慢性病家族病史者。五、停經前婦女屬於高健檢組擁有顯著較高機率於停經後會歸類於高健檢組，顯示出停經前若具有高健檢行為者其健檢行為的顯著延續性；然而，本研究也發現停經前屬於高健檢組在停經後也同時擁有較高的機率會歸類於高醫療使用組，其原因則與多重慢性疾病以及家族病史背景具有顯著相關。六、停經後婦女之健康服務使用可區分為高健檢組、高醫療組以及低使用組，其中高醫療使用組占有10%，低使用組也占有40%。七、停經後婦女屬於高醫療使用組之特質包括: 高齡、無偶、低教育程度、大陸省份籍貫、居住於南部地區、複雜式居住內容、抽菸/嚼檳榔/無規律運動習慣者、具糖尿病個人病史以及慢性病家族病史者。總結來說，本研究實證停經後婦女之個別差異性具有高度的群聚分類，各不同分類與家庭和社會經濟條件支持相關。從健康促進的政策思考，可針對本文所列舉之人口學特質、社會經濟因子及疾病狀況等面向提供民眾獲得正確停經亦或更年期資訊，避免未來高醫療服務使用之情形。[[abstract]]Menopause is one of the important events in the life course of women, and the impact from menopause on not only physical but also psychological aspect. More and more research indicated that the physiological and psychological affect during menopause had random effects among individuals; in other words, individual differences exist in subjective feelings, symptom distress, symptom severity, coping strategies, etc. which reflect to the variance in the use of health care services.However, different groups divided by frequency of using health care services before and after menopause, were compared systematically to analysis interrelation between socio-economic status and health history, further to clarify individual differences in menopause and the use of health care service. In this study, latent class analysis was applied to data from "National Health Interview Survey" in 2009 from National Institutes of Health, and followings were concluded:1.Compare to premenopausal, postmenopausal women were 2-3 times more in the frequency of using health care services (including outpatient service, emergency and inpatient service).2.In comparison to premenopausal, postmenopausal women had a higher use of health services besides Pap smear, non-government grants of adult health examination and internet searching health information. 3.Health service utilization in premenopausal women may be divided into high and low use of health examination which held 60% of this population. 4.Characteristics of premenopausal women in the group of low use of health examination included young adults, single, low education level, living in the non-northern region of Taiwan, not resident with their spouse, smoking/chewing betel nut / no regular exercise habit, no chronic disease and no family history of chronic disease.5.Premenopausal women belonging to high use in health examination had significant higher chance to be in high use in health examination group after menopause; nonetheless, premenopausal women in high use in health examination group also had higher probability to be in high use in medical service after menopause, it was significantly related to personal history or family history of chronic disease. 6.Health care utilization in postmenopausal women may be divided into three different groups, high use in health examination, high use in medical service and low use in health examination and medical. Ten percent of the population occupied in high use in medical service group, and 40% in low use in health examination and medical group.7.Characteristics of postmenopausal women in the high use in medical service included elderly, widow, low education level, Chinese origin, living in the southern region of Taiwan, complicated residency, smoking/chewing betel nut/no regular exercise habit, diabetic and with family history of chronic diseases.In conclusion, this study proved that individual differences in postmenopausal women had a high degree of clustering classification, and each group related to family and socio-economic status. In the perspective of health promotion, demographic characteristics, socioeconomic status and diseased states provided in the study offered people correct information about medical use during and after menopause to avoid high medical utilization in the future

Endodermal pouch-expressed dmrt2b is important for pharyngeal cartilage formation

Pharyngeal pouches, a series of outpocketings derived from the foregut endoderm, are essential for craniofacial skeleton formation. However, the molecular mechanisms underlying endodermal pouch-regulated head cartilage development are not fully understood. In this study, we find that zebrafish dmrt2b, a gene encoding Doublesex- and Mab-3-related transcription factor, is specifically expressed in endodermal pouches and required for normal pharyngeal cartilage development. Loss of dmrt2b doesn't affect cranial neural crest (CNC) specification and migration, but leads to prechondrogenic condensation defects by reducing cxcl12b expression after CNC cell movement into the pharyngeal arches. Moreover, dmrt2b inactivation results in reduced proliferation and impaired differentiation of CNC cells. We also show that dmrt2b suppresses crossveinless 2 expression in endodermal pouches to maintain BMP/Smad signaling in the arches, thereby facilitating CNC cell proliferation and chondrogenic differentiation. This work provides insight into how transcription factors expressed in endodermal pouches regulate pharyngeal skeleton development through tissue–tissue interactions

Synthesis, Crystal Structure, Absolute Configuration and Antitumor Activity of the Enantiomers of 5-Bromo-2-chloro-N-(1-phenylethyl)pyridine-3-sulfonamide

Pyridinesulfonamide is an important fragment which has a wide range of applications in novel drugs. R- and S-isomers of 5-bromo-2-chloro-N-(1-phenylethyl)pyridine-3-sulfonamide have been synthesized, and the stereostructures have been researched. Single crystals of both compounds were obtained for X-ray analysis, and the absolute configurations (ACs) have been further confirmed by electronic circular dichroism (ECD), optical rotation (OR) and quantum chemical calculations. The crystal structures and calculated geometries were extremely similar, which permitted a comparison of the relative reliabilities of ACs obtained by ECD analyses and theoretical simulation. In addition, the effect of stereochemistry on the PI3Kα kinase and anticancer activity were investigated. Compounds 10a and 10b inhibit the activity of PI3Kα kinase with IC50 values of 1.08 and 2.69 μM, respectively. Furthermore, molecular docking was performed to analyze the binding modes of R- and S-isomers

Lung cancer mortality among women in Xuan Wei, China: a comparison of spatial clustering detection methods

The identification of spatial clusters of lung cancer mortality can be a useful instrument in detecting locations with high risk of this disease. This study compared 2 methods for identifying spatial clusters of village-level women lung cancer mortality rates in Xuan Wei. One used a local indicator of spatial association to detect which groups of neighboring villages had lung cancer mortality rates that were significantly related to each other. The other was a spatial scan technique that calculated a maximum likelihood ratio of lung cancer deaths relative to the underlying population in order to identify the group of villages with relatively higher risk. As each technique based its cluster detection process on its own criteria, different clusters of villages were identified. However, the overlapping indicated that the 2 methods illustrated different components of the same clusters. These spatial analytic techniques were complementary to each other and can be used jointly rather than separately