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The authors sequenced the genome of an isolate of E. coli obtained from a German girl with bloody diarrhea and shared the data online with other researchers, facilitating rapid assembly of the genome. Escherichia coli is a widespread commensal of the mammalian gut and a versatile pathogen. 1 , 2 Enterovirulent strains of E. coli are classified into a number of overlapping pathotypes, which include Shiga-toxin–producing, enterohemorrhagic, and enteroaggregative varieties. 2 Enteroaggregative E. coli strains have been associated with sporadic and epidemic diarrhea and, in the laboratory, show a distinctive pattern of adherence to Hep-2 cells (termed aggregative, or “stacked brick”). 3 In Shiga-toxin–producing E. coli, the toxin is encoded on a prophage and inhibits protein synthesis within susceptible eukaryotic cells. Strains of enterohemorrhagic E. coli produce Shiga toxin and a specific protein secretion system (called a . . .

Residents of the Tibetan Plateau show heritable adaptations to extreme altitude. We sequenced 50 exomes of ethnic Tibetans, encompassing coding sequences of 92% of human genes, with an average coverage of 18x per individual. Genes showing population-specific allele frequency changes, which represent strong candidates for altitude adaptation, were identified. The strongest signal of natural selection came from endothelial Per-Arnt-Sim (PAS) domain protein 1 (EPAS1), a transcription factor involved in response to hypoxia. One single-nucleotide polymorphism (SNP) at EPAS1 shows a 78% frequency difference between Tibetan and Han samples, representing the fastest allele frequency change observed at any human gene to date. This SNP's association with erythrocyte abundance supports the role of EPAS1 in adaptation to hypoxia. Thus, a population genomic survey has revealed a functionally important locus in genetic adaptation to high altitude.

Respiratory diseases, marked by structural changes in the airways and lung tissues, can lead to reduced respiratory function and, in severe cases, respiratory failure. The side effects of current treatments, such as hormone therapy, drugs, and radiotherapy, highlight the need for new therapeutic strategies. Traditional Chinese Medicine (TCM) offers a promising alternative, leveraging its ability to target multiple pathways and mechanisms. Active compounds from Chinese herbs and other natural sources exhibit anti-inflammatory, antioxidant, antitumor, and immunomodulatory effects, making them valuable in preventing and treating respiratory conditions. Ferroptosis, a unique form of programmed cell death (PCD) distinct from apoptosis, necrosis, and others, has emerged as a key area of interest. However, comprehensive reviews on how natural products influence ferroptosis in respiratory diseases are lacking. This review will explore the therapeutic potential and mechanisms of natural products from TCM in modulating ferroptosis for respiratory diseases like acute lung injury (ALI), asthma, pulmonary fibrosis (PF), chronic obstructive pulmonary disease (COPD), lung ischemia–reperfusion injury (LIRI), pulmonary hypertension (PH), and lung cancer, aiming to provide new insights for research and clinical application in TCM for respiratory health.

Background: Respiratory diseases are common and frequent diseases. Due to the high pathogenicity and side effects of respiratory diseases, the discovery of new strategies for drug treatment is a hot area of research. Scutellaria baicalensis Georgi (SBG) has been used as a medicinal herb in China for over 2000 years. Baicalin (BA) is a flavonoid active ingredient extracted from SBG that BA has been found to exert various pharmacological effects against respiratory diseases. However, there is no comprehensive review of the mechanism of the effects of BA in treating respiratory diseases. This review aims to summarize the current pharmacokinetics of BA, baicalin-loaded nano-delivery system, and its molecular mechanisms and therapeutical effects for treating respiratory diseases. Method: This review reviewed databases such as PubMed, NCBI, and Web of Science from their inception to 13 December 2022, in which literature was related to “baicalin”, “ Scutellaria baicalensis Georgi”, “COVID-19”, “acute lung injury”, “pulmonary arterial hypertension”, “asthma”, “chronic obstructive pulmonary disease”, “pulmonary fibrosis”, “lung cancer”, “pharmacokinetics”, “liposomes”, “nano-emulsions”, “micelles”, “phospholipid complexes”, “solid dispersions”, “inclusion complexes”, and other terms. Result: The pharmacokinetics of BA involves mainly gastrointestinal hydrolysis, the enteroglycoside cycle, multiple metabolic pathways, and excretion in bile and urine. Due to the poor bioavailability and solubility of BA, liposomes, nano-emulsions, micelles, phospholipid complexes, solid dispersions, and inclusion complexes of BA have been developed to improve its bioavailability, lung targeting, and solubility. BA exerts potent effects mainly by mediating upstream oxidative stress, inflammation, apoptosis, and immune response pathways. It regulates are the NF-κB, PI3K/AKT, TGF-β/Smad, Nrf2/HO-1, and ERK/GSK3β pathways. Conclusion: This review presents comprehensive information on BA about pharmacokinetics, baicalin-loaded nano-delivery system, and its therapeutic effects and potential pharmacological mechanisms in respiratory diseases. The available studies suggest that BA has excellent possible treatment of respiratory diseases and is worthy of further investigation and development.

Background Targeted sequencing using oncopanels requires comprehensive assessments of accuracy and detection sensitivity to ensure analytical validity. By employing reference materials characterized by the U.S. Food and Drug Administration-led SEquence Quality Control project phase2 (SEQC2) effort, we perform a cross-platform multi-lab evaluation of eight Pan-Cancer panels to assess best practices for oncopanel sequencing. Results All panels demonstrate high sensitivity across targeted high-confidence coding regions and variant types for the variants previously verified to have variant allele frequency (VAF) in the 5–20% range. Sensitivity is reduced by utilizing VAF thresholds due to inherent variability in VAF measurements. Enforcing a VAF threshold for reporting has a positive impact on reducing false positive calls. Importantly, the false positive rate is found to be significantly higher outside the high-confidence coding regions, resulting in lower reproducibility. Thus, region restriction and VAF thresholds lead to low relative technical variability in estimating promising biomarkers and tumor mutational burden. Conclusion This comprehensive study provides actionable guidelines for oncopanel sequencing and clear evidence that supports a simplified approach to assess the analytical performance of oncopanels. It will facilitate the rapid implementation, validation, and quality control of oncopanels in clinical use.

Background High-throughput sequencing of blood cell-free DNA (cfDNA) techniques offer an opportunity to characterize and monitor cancer rapidly in a non-invasive and real-time manner. Nonetheless, there lacks a tool within therapeutic arsenal to identify multi-omics alterations simultaneously from a single biopsy. In current times, bisulfite-based sequencing detects 5mC and 5hmC at single-base resolution is the golden standard of DNA methylation, while the degradation of DNA and biased sequencing data are the problems of this method. Objective To identify the consistency analysis of methylation and genetic variation with single library, we presented a platform detecting multi-omics data simultaneously from a single blood biopsy using bisulfite-free method of genomic methylation sequencing (GM-seq) mediated by TET enzyme. Methods We detected methylomic and genetic changes simultaneously from a single blood biopsy in NA12878 and randomly chose ten blood biopsies from colorectal cancer or lung cancer patients to validate the ability of GM-seq. Results Similar cytosine methylation level between whole genome bisulfite sequencing (WGBS) and GM-seq were identified in NA12878. Moreover, longer insert size, CpGs coverage and GC distribution were outperformed than WGBS. In addition, the comparison of the single nucleotide polymorphism (SNP), insertion-deletion (Indel) and copy number variation (CNV) in NA12878 or ctDNA from liver cancer between GM-seq and whole genome sequencing (WGS) show a good consistency, indicating that this method is feasible for detecting genetic variation in blood. Conclusion In conclusion, our work demonstrated a method for identification of the methylated modification and genetic variations simultaneously from a single blood biopsy.

Surface polarized reflectance is related to its optical properties and observation geometry. It disturbs remote sensing of aerosol. In this study, we differentiated the polarized reflectance of a natural surface based on the normalized difference vegetation index and scattering angle, and the interband correlation coefficients were generally higher than that without differentiation. The spectral relationship was determined based on normalized difference vegetation index and scattering angle and then employed for aerosol retrieval from polarization and anisotropy of reflectances for atmospheric sciences coupled with observations from a lidar measurements. The retrieved aerosol optical depths (AODs) were contrasted with Aerosol Robotic Network results. The correlation coefficient between the retrieved and Aerosol Robotic Network AODs increased from 0.723 to 0.836, and the root‐mean‐square error reduced from 0.348 to 0.245 after considering the differentiated relationship. Thus, the accuracy of the retrieved AOD values was improved. Plain Language Summary The spectral relationship of surface polarized reflectance is related to the properties of land cover and observation geometry. Yet on many occasions of aerosol remote sensing, it is not sufficiently considered. In this study, we differentiated the polarized reflectance of a natural surface based on its properties and observation angles and the new spectral relationship was obtained using satellite measurements of 3 years. This relationship was applied to aerosol remote sensing and it provided more accurate results. It was demonstrated that surface property and observation angle values differentially contribute the surface polarized reflectance and considering the difference benefits the estimate of aerosol from satellite measurements. Key Points We determined the differentiated spectral relationships of surface polarized reflectance The accuracy of aerosol remote sensing was enhanced by using the relationships

Background Restriction Enzyme-based Reduced Representation Library (RRL) method represents a relatively feasible and flexible strategy used for Single Nucleotide Polymorphism (SNP) identification in different species. It has remarkable advantage of reducing the complexity of the genome by orders of magnitude. However, comprehensive evaluation for actual efficacy of SNP identification by this method is still unavailable. Results In order to evaluate the efficacy of Restriction Enzyme-based RRL method, we selected Tsp 45I enzyme which covers 266 Mb flanking region of the enzyme recognition site according to in silico simulation on human reference genome, then we sequenced YH RRL after Tsp 45I treatment and obtained reads of which 80.8% were mapped to target region with an 20-fold average coverage, about 96.8% of target region was covered by at least one read and 257 K SNPs were identified in the region using SOAPsnp software. Compared with whole genome resequencing data, we observed false discovery rate (FDR) of 13.95% and false negative rate (FNR) of 25.90%. The concordance rate of homozygote loci was over 99.8%, but that of heterozygote were only 92.56%. Repeat sequences and bases quality were proved to have a great effect on the accuracy of SNP calling, SNPs in recognition sites contributed evidently to the high FNR and the low concordance rate of heterozygote. Our results indicated that repeat masking and high stringent filter criteria could significantly decrease both FDR and FNR. Conclusions This study demonstrates that Restriction Enzyme-based RRL method was effective for SNP identification. The results highlight the important role of bias and the method-derived defects represented in this method and emphasize the special attentions noteworthy.

Key Points We re‐derived the spectral relationships of surface polarized reflectance over north China Aerosol optical depths over north China were retrieved from polarized satellite observations using the new relationships The seasonal variation of vegetable surface is the main disturbance in aerosol retrieval North China has one of the world's largest densities of atmospheric aerosol particles. The surface and aerosol properties in this area are complex. We evaluated the spectral relationship between surface polarized reflectances and introduced specific types of aerosol to improve the remote sensing of aerosols in this area. First, we searched for low‐aerosol‐loading areas (clean areas) based on Moderate resolution Imaging Spectroradiometer (MODIS) measurements between 2009 and 2011. Then, we recalculated the spectral relationships of surface polarized reflectance from corrected Polarization and Anisotropy of Reflectances for Atmospheric Sciences coupled with Observations from a Lidar (PARASOL) measurements. Finally, the re‐derived relationships and aerosol clustering modes for East Asia were applied using the adaptive land‐atmospheric decoupling (ALAD) algorithm to retrieve aerosol optical depth (AOD). We collected 914 PARASOL measured samples matched the site data of the aerosol robotic network (AERONET), within a wide AOD range between 2005 and 2013. The AOD trends from AERONET and PARASOL were similar. The slope of the regression line was 0.836, with a low intercept (0.032) and high correlation coefficient (0.854), and 53.6% of the retrieved AODs were within the range of the expected error. Compared with the MODIS daily AOD, we found that the variation in PARASOL results displayed a smooth tendency with the increase of AODs. The 914 sampling points were classified according to location and season to identify any discrepancies in the retrieved results. It was found that vegetation surfaces were responsible for most of the uncertainty due to their seasonal characteristics.

Lung adenocarcinoma (LUAD) represents a prevalent subtype of non-small cell lung cancer with a complex molecular landscape. Dysregulated cellular energetics, notably the interplay between hypoxia and glycolysis, has emerged as a hallmark feature of LUAD tumorigenesis and progression. In this study, we aimed to identify hypoxia and glycolysis related gene signatures and construct a prognostic model to enhance the clinical management of LUAD. A gene signature associated with hypoxia and glycolysis was established within the The Cancer Genome Atlas (TCGA) cohort and subsequently validated in the GSE31210 cohort. Additionally, a nomogram was formulated to aid in predictive modeling. Subsequently, an evaluation of the tumor microenvironment and immune checkpoints expression levels was conducted to discern disparities between low risk and high risk groups. Lastly, an exploration for drugs with potential effectiveness was carried out. Our analyses revealed a distinct hypoxia and glycolysis related gene signature consisting of 6 genes significantly associated with LUAD patient survival. Integration of these genes into the prognostic model demonstrated superior predictive accuracy for patient outcomes. Furthermore, we developed a user-friendly nomogram that effectively translates the model's prognostic information into a practical tool for clinical decision-making. This study elucidates the critical role of hypoxia and glycolysis related genes in LUAD and offers a novel prognostic model with promising clinical utility. This model has the potential to refine risk stratification and guide personalized therapeutic interventions, ultimately improving the prognosis of LUAD patients.