Comparison of safety and efficacy of tubeless vs. conventional mini percutaneous nephrolithotomy in patients with Escherichia coli bacteriuria.

To evaluate the safety and efficacy of tubeless percutaneous nephrolithotomy (PCNL) in patients with Escherichia coli (E. coli) bacteriuria. We conducted a retrospective review of 84 patients with E. coli bacteriuria who underwent PCNL. Patients were divided into two groups according to whether a nephrostomy tube is placed at the end of the procedure. Preoperative clinical data, surgical outcomes, and postoperative complications were compared. Then, regression analysis of factors predicting success rate of PCNL in patients with E. coli bacteriuria was performed. After PCNL, residual fragments ≤ 4 mm were considered as success. At baseline, the two groups were similar with regard to age, gender, BMI, underlying disease, hydronephrosis, stone characteristics, and urinalysis. Postoperative fever occurred in 1 patient (3.8%) in the tubeless PCNL group, and in 5 patients (8.6%) in the conventional PCNL group (p > 0.05). There were no significant differences in terms of successful rate, decrease in hemoglobin, pain scores, blood transfusion, and hospitalization expenses. However, the tubeless PCNL group had significantly shorter operative time (60 vs. 70 min, p = 0.033), indwelling time of catheter (2 vs. 4 days, p < 0.001), and hospital stays (3 vs. 5 days, p < 0.001) than the conventional PCNL group. In the analysis of factors predicting success, the stone diameter, stone burden, and operative time were associated with success rate of PCNL. It is safe and effective to perform tubeless PCNL in patients with E. coli bacteriuria. Compared to conventional PCNL, tubeless PCNL accelerates patient recovery and shortens hospital stays.

Prognostic Model Construction of Disulfidptosis-Related Genes and Targeted Anticancer Drug Research in Pancreatic Cancer.

Pancreatic cancer stands as one of the most lethal malignancies, characterized by delayed diagnosis, high mortality rates, limited treatment efficacy, and poor prognosis. Disulfidptosis, a recently unveiled modality of cell demise induced by disulfide stress, has emerged as a critical player intricately associated with the onset and progression of various cancer types. It has emerged as a promising candidate biomarker for cancer diagnosis, prognosis assessment, and treatment strategies. In this study, we have effectively established a prognostic risk model for pancreatic cancer by incorporating multiple differentially expressed long non-coding RNAs (DElncRNAs) closely linked to disulfide-driven cell death. Our investigation delved into the nuanced relationship between the DElncRNA-based predictive model for disulfide-driven cell death and the therapeutic responses to anticancer agents. Our findings illuminate that the high-risk subgroup exhibits heightened susceptibility to the small molecule compound AZD1208, positioning it as a prospective therapeutic agent for pancreatic cancer. Finally, we have elucidated the underlying mechanistic potential of AZD1208 in ameliorating pancreatic cancer through its targeted inhibition of the peroxisome proliferator-activated receptor-γ (PPARG) protein, employing an array of comprehensive analytical methods, including molecular docking and molecular dynamics (MD) simulations. This study explores disulfidptosis-related genes, paving the way for the development of targeted therapies for pancreatic cancer and emphasizing their significance in the field of oncology. Furthermore, through computational biology approaches, the drug AZD1208 was identified as a potential treatment targeting the PPARG protein for pancreatic cancer. This discovery opens new avenues for exploring targets and screening drugs for pancreatic cancer.

Preference for diagnosing and treating renal colic during pregnancy: a survey among Chinese urologists.

To explore the preference for diagnosing and treating renal colic during pregnancy among Chinese urologists. A questionnaire was designed using the Sojump® platform. WeChat, the largest social networking platform in China, was used to distribute the questionnaire to urologists at hospitals of all levels in China. In total, 110 responses were included. Of the respondents, 100.0% used ultrasound to diagnose renal colic during pregnancy, followed by magnetic resonance imaging (17.3%) and low-dose CT (3.6%). Phloroglucinol (80.9%) and progesterone (72.7%) were the most commonly used antispasmodics and analgesics. Opioid analgesics were not commonly used (12.7%). Most of the respondents (63.6%) indicated that no more than 20% of the patients needed surgical intervention. If surgery was unavoidable, 95.5% preferred temporary renal drainage, including ureteral stenting (92.7%) and percutaneous nephrostomy (2.7%). However, some respondents still preferred definitive stone treatment, such as ureteroscopy lithotripsy (3.6%) and percutaneous nephrolithotomy (0.9%). Moreover, there were no differences in the choices of urologists with different professional titles regarding diagnostic tools, most therapeutic medications, or surgical methods (p > 0.05). Ultrasound is the preferred tool for diagnosing renal colic during pregnancy. Low-dose CT is still not widely accepted. Pregnant patients with renal colic are initially treated conservatively. Urologists prefer ureteral stenting when there are clinical indications for intervention.

Covalent organic framework-sodium alginate-Ca2+-polyacrylic acid composite beads for convenient dispersive solid-phase extraction of neonicotinoid insecticides in fruit and vegetables.

Neonicotinoids, the fastest-growing class of insecticides, have posed a multi-media residue problem with adverse effects on environment, biodiversity and human health. Herein, covalent organic framework-sodium alginate-Ca2+-polyacrylic acid composite beads (CACPs), facilely prepared at room temperature, were used in convenient dispersive solid-phase extraction (dSPE) and combined with high-performance liquid chromatography (HPLC) for the detection of five neonicotinoid insecticides (thiamethoxam, acetamiprid, dinotefuran, clothianidin, imidacloprid). CACPs can be completely separated within 1 min without centrifugation. After seven adsorption/desorption cycles, it maintained high extraction efficiencies (>90%). The developed method exhibited a wide linear range (0.01 âˆ¼ 10 µg mL-1), low limits of detection (LODs, 0.0028 âˆ¼ 0.0031 mg kg-1), and good repeatability (RSD ≤ 8.11%, n = 3). Moreover, it was applied to the determination of five neonicotinoids in fruit and vegetables (peach, pear, lettuce, cucumber, tomato), and recoveries ranged from 73.6% to 116.2%.

[Regularity of ventilator-associated pneumonia induced by three common pathogens].

OBJECTIVE: To investigate the incidence and infection regularity of ventilator-associated pneumonia (VAP) in patients undergoing tracheal intubation and to provide reference for the prevention and treatment of VAP infection in the future. METHODS: A retrospective study was conducted to collect the microbial data of airway secretion cultures from 72 patients with endotracheal intubation admitted to the emergency ward of Shanghai Fifth People's Hospital from May 2020 to February 2021, and the species of microorganisms and intubation time were statistically analyzed. RESULTS: Among 72 patients with endotracheal intubation, males were more than females (58.33% vs. 41.67%); Patients over 60 years old accounted for 90.28%; pneumonia was the main primary disease, accounting for 58.33%. Pathogenic tests showed that: (1) 72 patients were infected with Acinetobacter baumannii (AB), Klebsiella pneumoniae (KP), and Pseudomonas aeruginosa (PA) 48 hours after intubation, 51.39% (37/72), 27.78% (20/72), and 26.39% (19/72), respectively. The infection rate of AB was significantly higher than that of KP and PA. Within 48 hours of intubation, the infection rates of AB, KP, and PA were 20.83% (15/72), 13.89% (10/72), and 4.17% (3/72), respectively. Of the 42 patients with primary pneumonia, 61.90% (26/42) were infected with one or more of the three pathogenic bacteria AB, KP, and PA 48 hours after intubation, indicating a change in the etiology of the pathogenic bacteria, with the main pathogenic bacteria transitioning from other pathogenic bacteria to AB, KP, and PA. (2) AB, KP, and PA were prone to cause late onset VAP (i.e., intubation ≥ 5 days). Respectively, among VAP patients infected with AB, late onset VAP accounted for 59.46% (22/37). Among patients infected with KP, 75.00% (15/20) had late onset VAP. Among patients infected with PA, late onset VAP accounted for 94.74% (18/19), indicating a higher proportion of late onset VAP caused by PA and KP. (3) Infection was closely related to intubation time, and the pipeline can be replaced according to the peak period of infection. AB and KP infections peaked within 4 days after intubation, reaching 57.69% (30/52) and 50.00% (15/30), respectively. It is recommended to replace the tubes or undergo sensitive antimicrobial therapy around 3-4 days after starting the machine. The proportion of PA infection after 7 days of intubation was 72.73% (16/22), and it was considered to replace the pipeline after 7 days. (4) Most of the three pathogenic bacteria, AB, KP, and PA were carbapenem resistant pathogens with multiple drug resistance. Except for PA, the infection rate of carbapenem resistant bacteria (CRAB, CRKP) was significantly higher than that of non-carbapenem resistant bacteria (AB, KP), accounting for 86.54% (45/52) and 66.67% (20/30) of the corresponding infection cases, respectively, while CRPA only accounts for 18.18% (4/22). CONCLUSIONS: The main differences in VAP infection caused by AB, KP, and PA pathogens are infection time, infection probability, and carbapenem resistance. Targeted prevention and treatment measures can be implemented for patients with intubation.

Impact of the Coronavirus Disease 2019 Pandemic on Leisure Screen Time and Eating Habits of Japanese High School Students: A Comparison between before and during the Pandemic.

This study aimed to determine whether adolescents' leisure screen time differed during the coronavirus disease 2019 (COVID-19) pandemic compared to before the pandemic, and to identify factors that affect leisure screen time among Japanese high school students. The Health Behavior in School Children questionnaire was used to investigate differences in eating habits and physical and mental health. The results showed that the leisure screen time of Japanese high school students was 2.6 h (SD = 1.4) before the pandemic, and 3.2 h (SD = 1.5) during the pandemic. The factors that increased leisure screen time were found to differ between boys and girls. No significant deterioration in physical and mental health was observed. The impact of the pandemic on eating habits differed in boys and girls. Boys reported "not feeling great about life" as a factor that increased leisure screen time during the pandemic, suggesting that negative emotions influenced the increase in leisure screen time. The pandemic had a significant impact on girls' leisure screen time. Longer screen time should be carefully monitored because it can lead to sleep disturbances, worsening of mental health, and obesity. Compared with before the pandemic, the health status of boys and girls changed little. Eating habits tended to improve for both boys and girls.

MiR-218-5p/EGFR Signaling in Arsenic-Induced Carcinogenesis.

BACKGROUND: Arsenic is a well-known carcinogen inducing lung, skin, bladder, and liver cancer. Abnormal epidermal growth factor receptor (EGFR) expression is common in lung cancer; it is involved in cancer initiation, development, metastasis, and treatment resistance. However, the underlying mechanism for arsenic-inducing EGFR upregulation remains unclear. METHODS: RT-PCR and immunoblotting assays were used to detect the levels of miR-218-5p and EGFR expression. The Luciferase assay was used to test the transcriptional activity of EGFR mediated by miR-218-5p. Cell proliferation, colony formation, wound healing, migration assays, tube formation assays, and tumor growth assays were used to study the function of miR-218-5p/EGFR signaling. RESULTS: EGFR and miR-218-5p were dramatically upregulated and downregulated in arsenic-induced transformed (As-T) cells, respectively. MiR-218-5p acted as a tumor suppressor to inhibit cell proliferation, migration, colony formation, tube formation, tumor growth, and angiogenesis. Furthermore, miR-218-5p directly targeted EGFR by binding to its 3'-untranslated region (UTR). Finally, miR-218-5p exerted its antitumor effect by inhibiting its direct target, EGFR. CONCLUSION: Our study highlights the vital role of the miR-218-5p/EGFR signaling pathway in arsenic-induced carcinogenesis and angiogenesis, which may be helpful for the treatment of lung cancer induced by chronic arsenic exposure in the future.

METTL3-mediated N6-methyladenosine modification and HDAC5/YY1 promote IFFO1 downregulation in tumor development and chemo-resistance.

Ovarian cancer (OC) is a malignant tumor that seriously threatens women's health. Due to the difficulty of early diagnosis, most patients exhibit advanced disease or peritoneal metastasis at diagnosis. We discovered that IFFO1 is a novel tumor suppressor, but its role in tumorigenesis, development and chemoresistance is unknown. In this study, IFFO1 levels were downregulated across cancers, leading to the acceleration of tumor development, metastasis and/or cisplatin resistance. Overexpression of IFFO1 inhibited the translocation of ß-catenin to the nucleus and decreased tumor metastasis and cisplatin resistance. Furthermore, we demonstrated that IFFO1 was regulated at both the transcriptional and posttranscriptional levels. At the transcriptional level, the recruitment of HDAC5 inhibited IFFO1 expression, which is mediated by the transcription factor YY1, and the METTL3/YTHDF2 axis regulated the mRNA stability of IFFO1 in an m6A-dependent manner. Mice injected with IFFO1-overexpressing cells had lower ascites volumes and tumor weights throughout the peritoneal cavity than those injected with parental cells expressing the vector control. In conclusion, we demonstrated that IFFO1 is a novel tumor suppressor that inhibits tumor metastasis and reverses drug resistance in ovarian cancer. IFFO1 was downregulated at both the transcriptional level and posttranscriptional level by histone deacetylase and RNA methylation, respectively, and the IFFO1 signaling pathway was identified as a potential therapeutic target for cancer.

Epigenetic Regulation in Chromium-, Nickel- and Cadmium-Induced Carcinogenesis.

Environmental and occupational exposure to heavy metals, such as hexavalent chromium, nickel, and cadmium, are major health concerns worldwide. Some heavy metals are well-documented human carcinogens. Multiple mechanisms, including DNA damage, dysregulated gene expression, and aberrant cancer-related signaling, have been shown to contribute to metal-induced carcinogenesis. However, the molecular mechanisms accounting for heavy metal-induced carcinogenesis and angiogenesis are still not fully understood. In recent years, an increasing number of studies have indicated that in addition to genotoxicity and genetic mutations, epigenetic mechanisms play critical roles in metal-induced cancers. Epigenetics refers to the reversible modification of genomes without changing DNA sequences; epigenetic modifications generally involve DNA methylation, histone modification, chromatin remodeling, and non-coding RNAs. Epigenetic regulation is essential for maintaining normal gene expression patterns; the disruption of epigenetic modifications may lead to altered cellular function and even malignant transformation. Therefore, aberrant epigenetic modifications are widely involved in metal-induced cancer formation, development, and angiogenesis. Notably, the role of epigenetic mechanisms in heavy metal-induced carcinogenesis and angiogenesis remains largely unknown, and further studies are urgently required. In this review, we highlight the current advances in understanding the roles of epigenetic mechanisms in heavy metal-induced carcinogenesis, cancer progression, and angiogenesis.

Chromium (VI)-induced ALDH1A1/EGF axis promotes lung cancer progression.

Cr(VI) is broadly applied in industry. Cr(VI) exposure places a big burden on public health, thereby increasing the risk of lung squamous cell carcinoma (LUSC). The mechanisms underlying Cr(VI)-induced LUSC remain largely elusive. Here, we report that the cancer stem cell (CSC)/tumour-initiating cell (TIC)-like subgroup within Cr(VI)-transformed bronchial epithelial cells (CrT) promotes lung cancer tumourigenesis. Mechanistically, Cr(VI) exposure specifically increases the expression levels of aldehyde dehydrogenase 1A1 (ALDH1A1), a CSC marker, through KLF4-mediated transcription. ALDH1A1 maintains self-renewal of CrT/TICs and facilitates the expression and secretion of EGF from CrT/TICs, which subsequently promotes the activation of EGFR signalling in differentiated cancer cells and tumour growth of LUSC. In addition, the ALDH1A1 inhibitor A37 and gemcitabine synergistically suppress LUSC progression. Importantly, high ALDH1A1 expression levels are positively correlated with advanced clinical stages and predict poor survival in LUSC patients. These findings elucidate how ALDH1A1 modulates EGF secretion from TICs to facilitate LUSC tumourigenesis, highlighting new therapeutic strategies for malignant lung cancers.

Corrigendum: Regulation of microrna-497-targeting AKT2 influences tumor growth and chemoresistance to cisplatin in lung cancer.

[This corrects the article DOI: 10.3389/fcell.2020.00840.].

The active functional microbes contribute differently to soil nitrification and denitrification potential under long-term fertilizer regimes in North-East China.

Nitrogen (N) cycling microorganisms mediate soil nitrogen transformation processes, thereby affecting agricultural production and environment quality. However, it is not fully understood how active N-cycling microbial community in soil respond to long-term fertilization, as well as which microorganisms regulate soil nitrogen cycling in agricultural ecosystem. Here, we collected the soils from different depths and seasons at a 29-year fertilization experimental field (organic/chemical fertilizer), and investigated the transcriptions of N-cycling functional genes and their contribution to potential nitrification and denitrification. We found that long-term fertilization exerted significant impacts on the transcript abundances of nitrifiers (AOA amoA, AOB amoA and hao) and denitrifiers (narG and nosZ), which was also notably influenced by season variation. The transcriptions of AOA amoA, hao, and narG genes were lowest in autumn, and AOB amoA and nosZ transcript abundances were highest in autumn. Compared to no fertilization, soil potential nitrification rate (PNR) was reduced in fertilization treatments, while soil potential denitrification rate (PDR) was significantly enhanced in organic combined chemical fertilizer treatment. Both PNR and PDR were highest in 0-20 cm among the tested soil depths. Path model indicated active nitrifiers and denitrifiers had significant impact on soil PNR and PDR, respectively. The transcriptions of AOA amoA and nxr genes were significantly correlated with soil PNR (Pearson correlation, r > 0.174, p < 0.05). Significant correlation of napA and nosZ transcriptions with soil PDR (Pearson correlation, r > 0.234, p < 0.05) was also revealed. Random forest analysis showed that SOC content and soil pH were the important factors explaining the total variance of active nitrifers and denitrifiers, respectively. Taken together, long-term fertilization regimes reduced soil PNR and enhanced PDR, which could be attributed to the different responses of active N-cycling microorganisms to soil environment variations. This work provides new insight into the nitrogen cycle, particularly microbial indicators in nitrification and denitrification of long-term fertilized agricultural ecosystems.

Transcriptome and Metabolome Analyses Reveals the Pathway and Metabolites of Grain Quality Under Phytochrome B in Rice (Oryza sativa L.).

BACKGROUND: Grain size and chalkiness is a critical agronomic trait affecting rice yield and quality. The application of transcriptomics to rice has widened the understanding of complex molecular responsive mechanisms, differential gene expression, and regulatory pathways under varying conditions. Similarly, metabolomics has also contributed drastically for rice trait improvements. As master regulators of plant growth and development, phys influence seed germination, vegetative growth, photoperiodic flowering, shade avoidance responses. OsPHYB can regulate a variety of plant growth and development processes, but little is known about the roles of rice gene OsPHYB in modulating grain development. RESULTS: In this study, rice phytochrome B (OsPHYB) was edited using CRISPR/Cas9 technology. We found that OsPHYB knockout increased rice grain size and chalkiness, and increased the contents of amylose, free fatty acids and soluble sugar, while the gel consistency and contents of proteins were reduced in mutant grains. Furthermore, OsPHYB is involved in the regulation of grain size and chalk formation by controlling cell division and complex starch grain morphology. Transcriptomic analysis revealed that loss of OsPHYB function affects multiple metabolic pathways, especially enhancement of glycolysis, fatty acid, oxidative phosphorylation, and antioxidant pathways, as well as differential expression of starch and phytohormone pathways. An analysis of grain metabolites showed an increase in the free fatty acids and lysophosphatidylcholine, whereas the amounts of sugars, alcohols, amino acids and derivatives, organic acids, phenolic acids, alkaloids, nucleotides and derivatives, and flavonoids decreased, which were significantly associated with grain size and chalk formation. CONCLUSIONS: Our study reveals that, OsPHYB plays an important regulatory role in the growth and development of rice grains, especially grain size and chalkiness. Furthermore, OsPHYB regulates grain size and chalkiness formation by affecting gene metabolism interaction network. Thus, this study not only revealed that OsPHYB plays a vital role in regulating grain size and chalkiness of rice but reveal new functions and highlighted the importance and value of OsPHYB in rice grain development and provide a new strategy for yield and quality improvement in rice breeding.

Cyclophilin A binds to AKT1 and facilitates the tumorigenicity of Epstein-Barr virus by mediating the activation of AKT/mTOR/NF-κB positive feedback loop.

The AKT/mTOR and NF-κB signalings are crucial pathways activated in cancers including nasopharyngeal carcinoma (NPC), which is prevalent in southern China and closely related to Epstein-Barr virus (EBV) infection. How these master pathways are persistently activated in EBV-associated NPC remains to be investigated. Here we demonstrated that EBV-encoded latent membrane protein 1 (LMP1) promoted cyclophilin A (CYPA) expression through the activation of NF-κB. The depletion of CYPA suppressed cell proliferation and facilitated apoptosis. CYPA was able to bind to AKT1, thus activating AKT/mTOR/NF-κB signaling cascade. Moreover, the use of mTOR inhibitor, rapamycin, subverted the activation of the positive feedback loop, NF-κB/CYPA/AKT/mTOR. It is reasonable that LMP1 expression derived from initial viral infection is enough to assure the constant potentiation of AKT/mTOR and NF-κB signalings. This may partly explain the fact that EBV serves as a tumor-promoting factor with minimal expression of the viral oncoprotein LMP1 in malignancies. Our findings provide new insight into the understanding of causative role of EBV in tumorigenicity during latent infection.

Epigenetic Dysregulations in Arsenic-Induced Carcinogenesis.

Arsenic is a crucial environmental metalloid whose high toxicity levels negatively impact human health. It poses significant health concerns to millions of people in developed and developing countries such as the USA, Canada, Bangladesh, India, China, and Mexico by enhancing sensitivity to various types of diseases, including cancers. However, how arsenic causes changes in gene expression that results in heinous conditions remains elusive. One of the proposed essential mechanisms that still has seen limited research with regard to causing disease upon arsenic exposure is the dysregulation of epigenetic components. In this review, we have extensively summarized current discoveries in arsenic-induced epigenetic modifications in carcinogenesis and angiogenesis. Importantly, we highlight the possible mechanisms underlying epigenetic reprogramming through arsenic exposure that cause changes in cell signaling and dysfunctions of different epigenetic elements.

ROS and miRNA Dysregulation in Ovarian Cancer Development, Angiogenesis and Therapeutic Resistance.

The diverse repertoires of cellular mechanisms that progress certain cancer types are being uncovered by recent research and leading to more effective treatment options. Ovarian cancer (OC) is among the most difficult cancers to treat. OC has limited treatment options, especially for patients diagnosed with late-stage OC. The dysregulation of miRNAs in OC plays a significant role in tumorigenesis through the alteration of a multitude of molecular processes. The development of OC can also be due to the utilization of endogenously derived reactive oxygen species (ROS) by activating signaling pathways such as PI3K/AKT and MAPK. Both miRNAs and ROS are involved in regulating OC angiogenesis through mediating multiple angiogenic factors such as hypoxia-induced factor (HIF-1) and vascular endothelial growth factor (VEGF). The NAPDH oxidase subunit NOX4 plays an important role in inducing endogenous ROS production in OC. This review will discuss several important miRNAs, NOX4, and ROS, which contribute to therapeutic resistance in OC, highlighting the effective therapeutic potential of OC through these mechanisms.

Epigenetic alterations of CXCL5 in Cr(VI)-induced carcinogenesis.

Chronic exposure to hexavalent chromium compounds [Cr(VI)] is associated with an increased risk of cancers, but the molecular mechanisms remain to be elucidated. In this study, we found that CXCL5 levels in peripheral blood monocytes (PBMCs) and plasma from workers with occupational exposure to Cr(VI) were dramatically upregulated compared to non-exposure healthy subjects, and plasma C-X-C Motif Chemokine Ligand 5 (CXCL5) CXCL5 levels were positively correlated with Cr concentrations in subjects' toenails. Zinc chromate exposed mice showed higher levels of CXCL5 and its receptor CXCR2 in lung tissues, and in PBMCs. Similar CXCL5 upregulation was evident in Cr(VI)-induced transformed (Cr-T) cells with long-term Cr(VI) treatment. Mechanistic studies showed that elevated CXCL5 expression levels were regulated by Cr(VI)-induced histone modifications and DNA hypomethylation, and that the c-Myc/p300 complex was a key upstream regulator of histone H3 acetylation. CXCL5 overexpression promoted Cr(VI)-induced the epithelial to mesenchyme transition (EMT) by upregulating zinc finger E-box binding homeobox 1 (ZEB1) to promote tumor development. Our findings identify a novel mechanism by which CXCL5 is upregulated and promotes EMT and carcinogenesis upon chronic Cr(VI) exposure. Our work also implies that CXCL5 mRNA and protein levels will elevate in PBMCs and serum after occupational Cr(VI) exposure, which may be a potential target and biomarker for cancer prevention and health surveillance among populations exposed to Cr(VI).

Oxidized PUFAs Increase Susceptibility of Mice to Salmonella Infection by Diminishing Host's Innate Immune Responses.

Dietary ω-3 PUFAs are highly prone to oxidation, and this may potentially limit their application in the health-promoting field. Here, we sought to investigate whether and how oxidized PUFAs modulate the susceptibility of mice to Salmonella typhimurium (S. Tm) infection. Algae oil (AO) and oxidized algae oil (ox-AO) were administered to the C57BL/6 mice prior to S. Tm infection. Compared to the S. Tm group, ox-AO increased bacterial burden in systemic and intestinal tissues, downregulated host anti-infection responses, and developed worse colitis. In macrophages, ox-AO decreased both phagocytosis of S. Tm and clearance of intracellular bacteria and dampened the activation of mitogen-activated protein kinase (MAPK), NF-κB, and autophagy pathways. Furthermore, ox-AO diminished LPS-induced inflammatory cytokine production and S. Tm induced NLRC4 inflammasome activation. This study reveals that oxidized PUFAs may contribute to the development of enteric infections and regular monitoring of the oxidation status in commercial PUFA supplements to prevent their potential adverse impact on human health.

Bsu polymerase-mediated fluorescence coding for rapid and sensitive detection of 8-oxo-7,8-dihydroguanine in telomeres of cancer cells.

Guanine is the most susceptible to oxidation among all the DNA bases, and 8-oxo-7,8-dihydroguanine (OG) is one of main oxidation products that can occur in any part of chromosomal DNA. OG in the telomere sequence is associated with telomere shortening, cell aging, and dysfunction, and it may induce cancers. The accurate detection of OG in telomeres is important to early clinical diagnosis and molecular research. Herein, we develop a simple and rapid method to sensitively measure 8-oxo-7,8-dihydroguanine (OG) in telomeres of cancer cells by using Bsu polymerase-mediated fluorescence coding. This method is very simple without the requirement for any nucleic acid amplification or specific restriction enzyme recognition reaction, and Bsu polymerase can selectively incorporate Cy5-dATP into the opposite site of OG, endowing this method with good specificity. Moreover, the introduction of single-molecule detection significantly improves the sensitivity. This method can detect OG within 70 min with a limit of detection (LOD) of 2.45 × 10-18 M, and it can detect OG in genomic DNA extracted from H2O2-treated HeLa cells with a LOD of 0.0094 ng, holding great potential in disease-specific gene damage research and early clinic diagnosis.