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Background: Staphylococcus aureus is one of the most important bacteria in human colonization and infection. Clonal complex1 (CC1) is one of the largest and most important S. aureus CCs, and it is a predominant clone in S. aureus colonization and can cause a series of S. aureus infections including bloodstream infections. No studies on the relationship of CC1 S. aureus between colonization and infection have been published. Methods: To figure out if there are some significant factors in CC1 S. aureus help its colonization or infection, 15 CC1 S. aureus isolates including ten from colonization and five from bloodstream infections were enrolled in this study. Whole-genome sequencing and bioinformatics analysis were performed. Results: Virulence factor regulators XdrA, YSIRK signal peptide, CPBP family and OmpR family specifically found in infection isolates can promote virulence factors and enhance the pathogenicity of S. aureus. In addition, some significant differences in metabolism and human diseases were discovered between colonization and infection. Fst family of type I toxin–antitoxin system that mainly maintains stable inheritance was specifically found in CC1 S. aureus colonization isolates and might help S. aureus survive for colonization. No significant differences in genomic evolutionary relationship were found among CC1 S. aureus isolates between colonization and infection. Conclusions: Virulence factor regulators and metabolic state can promote CC1 S. aureus pathogenic process compared with colonization, and it seems that the strains of colonization origin cannot have pathogenic potential. Experimental confirmation and a bigger number of CC1 S. aureus strains are necessary for further study about the details and mechanism between colonization and infection. [ABSTRACT FROM AUTHOR]

Background: Bufalin (BA) is a potent traditional Chinese medicine derived from toad venom. It has shown significant antitumor activity, but its use is limited by cardiotoxicity, which necessitates innovative delivery methods, such as rod-shaped mesoporous silica nanoparticles (rMSNs). rMSNs have been extensively employed for reducing drug toxicity and for controlled or targeted drug delivery in tumor therapy. However, their potential in delivering BA has not been completely elucidated. Therefore, in this study, BA-loaded rMSNs (BA-rMSNs) were developed to investigate their potential and mechanism in impairing colon cancer cells. Methods: rMSNs were developed via the sol‒gel method. Drug encapsulation efficiency and loading capacity were determined to investigate the advantages of the rMSN in loading BA. The antiproliferative activities of the BA-rMSNs were investigated via 5-ethynyl-2'-deoxyuridine and CCK-8. To evaluate cell death, Annexin V-APC/PI apoptotic and calcein-AM/PI double staining were performed. Western blotting, oil red O staining, and Nile red solution were employed to determine the ability of BA-rMSNs to regulate lipophagy. Results: The diameter of the BA-rMSNs was approximately 60 nm. In vitro studies demonstrated that BA-rMSNs markedly inhibited HCT 116 and HT-29 cell proliferation and induced cell death. In vivo studies revealed that BA-rMSNs reduced BA-mediated cardiotoxicity and enhanced BA tumor targeting. Mechanistic studies revealed that BA-rMSNs blocked lipophagy. Conclusions: rMSNs reduced BA-mediated cardiotoxicity and impaired the growth of colon cancer cells. Mechanistically, antitumor activity depends on lipophagy. [ABSTRACT FROM AUTHOR]

Background: The kidney is exceptionally vulnerable during sepsis, often resulting in sepsis-associated acute kidney injury (SA-AKI), a condition that not only escalates morbidity but also significantly raises sepsis-related mortality rates. Circular RNA circ_001653 has been previously reported to be upregulated in the serum of SA-AKI patients, while the role and underlying mechanism of circ_001653 in SA-AKI remains unknown. In this study, we aimed to explore the functional role and the molecular mechanism of circ_001653 in the pathogenesis of SA-AKI. Methods: LPS-stimulated HK-2 cells and ligation and perforation of cecum (CLP)-induced rats were used as in vitro and in vivo models of SA-AKI. The target gene expression levels were measured using qRT-PCR and western blot. Renal function (BUN, sCr, uNGAL, and uKIM-1), and renal pathological changes were detected in septic mice. TUNEL and EdU assays were conducted to measure apoptosis and proliferation rates in vitro. DCFH-DA staining was used to detect ROS levels in vitro and in vivo. Oxidative stress markers (SOD, GSH-Px, MDA, and SOD), and inflammation markers (IL-1β, IL-6, and TNF-α) were determined using commercial kits both in vitro and in vivo. Additionally, gain-and-loss-of-function assays and mechanistic experiments were conducted to explore the regulatory role of circ_001653 in SA-AKI pathogenesis. Results: Data showed that circ_001653 expression was high in LPS-stimulated HK-2 cells and CLP-induced rat renal tissue and was mainly localized in the cytoplasm. Notably, circ_001653 silencing alleviated SA-AKI by reducing apoptosis and alleviating oxidative stress and inflammation in HK-2 cells and renal tissue of rats. Mechanistically, it was found that circ_001653 alleviated SA-AKI by recruiting BUD13 to activate the KEAP1/Nrf2/HO-1 signaling pathway. Conclusions: To summarize, our study is the first to reveal elevated expression of circ_001653 in sepsis-associated AKI, and its downregulation effectively attenuates AKI by reducing apoptosis, inflammation, and oxidative stress. Mechanistically, circ_001653 exerts its effects by recruiting BUD13 to activate the KEAP1/Nrf2/HO-1 signaling pathway. These findings suggest circ_001653 as a potential therapeutic target for the drug development of sepsis-associated AKI. [ABSTRACT FROM AUTHOR]

Cancer immunotherapy has sparked a wave of cancer research, driven by recent successful proof-of-concept clinical trials. However, barriers are emerging during its rapid development, including broad adverse effects, a lack of reliable biomarkers, tumor relapses, and drug resistance. Integration of nanomedicine may ameliorate current cancer immunotherapy. Ultra-large surface-to-volume ratio, extremely small size, and easy modification surface of nanoparticles enable them to selectively detect cells and kill cancer cells in vivo. Exciting synergistic applications of the two approaches have emerged in treating various cancers at the intersection of cancer immunotherapy and cancer nanomedicine, indicating the potential that the combination of these two therapeutic modalities can lead to new paradigms in the treatment of cancer. This review discusses the status of current immunotherapy and explores the possible opportunities that the nanomedicine platform can make cancer immunotherapy more powerful and precise by synergizing the two approaches. [ABSTRACT FROM AUTHOR]

Background: Significant concomitants of the sick role maladaptation in colorectal cancer (CRC) patients include inappropriate cognitions, emotional states, and overt conducts associated to disease. This protocol was developed to implement and evaluate the effects of a self-led, virtual reality-based cognitive behavioral therapy (VR-CBT) on the sick role adaptation among working-age CRC patients. Methods: This is an assessor-blinded, randomized controlled trail that adheres to the SPIRIT 2013 Statement guidelines. A total of 60 working-age CRC patients will be recruited from the colorectal wards of a cancer center and randomly assigned to the VR-CBT group or attention control (AC) group. The VR-CBT group will receive a 7-sessions VR-CBT targeted to sick role adaptation, while the AC group will receive weekly attention at the same time the VR-CBT group receives the intervention. The sick role adaptation, anxiety and depression, illness perceptions, and quality of life will be measured at baseline, 1, 2 and 3-month after completion of the intervention. Side-effects related to VR in the VR-CBT group will be measured at the end of each session. The participants will receive invitations to participate in semi-structured interviews to explore their experiences with the intervention. Discussion: The positive outcomes and user experience of VR-CBT will advance researches on the effectiveness of psychosocial interventions that aims to promote adaptation to the unexpected sick role on cancer populations. This protocol can be tested as an accessible and feasible alternative to traditional high-cost treatment in a randomized controlled study to improve the outcomes of younger cancer survivors. Trial registration. The protocol was registered on 21 June, 2023 in Chinese Clinical Trial Registry (No.: ChiCTR2300072699) at https://www.chictr.org.cn/. [ABSTRACT FROM AUTHOR]

Enterotoxigenic E. coli is one of the bacterial pathogens contributing to the global resistance crisis in public health and animal husbandry. The problem of antibiotic resistance is becoming more and more serious, and phage is considered one of the potential alternatives to antibiotics that could be utilized to treat bacterial infections. Our study isolated and identified a lytic phage PGX1 against multidrug-resistant enterotoxigenic E. coli EC6 strain from sewage. The phage lysis profile revealed that PGX1 exhibited a lytic effect on multidrug-resistant enterotoxigenic E. coli strains of serotype O60. Through phage whole genome sequencing and bioinformatics analysis, PGX1 was found to be the class Caudoviricetes, family Autographiviridae, genus Teseptimavirus. The length of the PGX1 genome is about 37,009 bp, containing 54 open reading frames (ORFs). Notably, phage PGX1 lacks any lysogenic-related genes or virulence genes. Furthermore, phage PGX1 demonstrates strong adaptability, tolerance, and stability in various pH (pH4-10) and temperatures (4–40°C). The in vivo and in vitro tests demonstrated that phage PGX1 significantly removes and inhibits the formation of multidrug-resistant EC6 biofilm and effectively controls the Galleria mellonella larvae and enterotoxigenic E. coli EC6 during mice infection. In conclusion, the above findings demonstrated that phage PGX1 may be a novel antimicrobial agent to control multidrug-resistant E. coli infections. [ABSTRACT FROM AUTHOR]

Background: Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with a five-year survival rate of approximately 10%. Genetic mutations are pivotal drivers in PDAC pathogenesis, but recent investigations also revealed the involvement of non-genetic alterations in the disease development. In this study, we undertook a multi-omics approach, encompassing ATAC-seq, RNA-seq, ChIP-seq, and Hi-C methodologies, to dissect gene expression alterations arising from changes in chromosome accessibility and chromatin three-dimensional interactions in PDAC. Results: Our findings indicate that chromosomal structural alterations can lead to abnormal expressions on key genes during PDAC development. Notably, overexpression of oncogenes FGFR2, FOXA2, CYP2R1, and CPOX can be attributed to the augmentation of promoter accessibility, coupled with long-range interactions with distal elements. Additionally, our findings indicate that chromosomal structural alterations caused by genomic instability can lead to abnormal expressions in PDACs. As an example, by analyzing chromosomal changes, we identified a putative oncogenic gene, LPAR1, which shows upregulated expression in both PDAC cell lines and clinical samples. The overexpression is correlated with alterations in LPAR1-associated 3D genome structure and chromatin state. We further demonstrated that high LPAR1 activity is required for enhanced PDAC cell migration in vitro. Conclusions: Collectively, our findings reveal that the chromosomal conformational alterations, in addition to the well-known genetic mutations, are critical for PDAC tumorigenesis. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to determine the independent and incremental values of advanced oxidative protein product (AOPP), interleukin 6 (IL-6), and growth differentiation factor 15 (GDF15) in identifying arteriosclerosis in patients with obstructive sleep apnea (OSA). Methods: A total of 104 individuals diagnosed with OSA by polysomnography were recruited in our study. Arteriosclerosis was defined by measuring the ultrafast pulse wave velocity of the carotid artery. Peripheral venous blood samples were collected to analyze the levels of AOPP, IL-6, and GDF15 utilizing commercially available enzyme-linked immunosorbent assays. Results: Compared to OSA patients without arteriosclerosis, those with arteriosclerosis exhibited significantly higher levels of AOPP, IL-6, and GDF15. GDF15 remained significantly associated with arteriosclerosis even after accounting for clinical factors such as age, gender, body mass index, systolic blood pressure, fasting blood glucose, smoking, and the apnea–hypoxia index (AHI). GDF15 demonstrated the largest area under the curve (AUC) for identifying arteriosclerosis in OSA patients (AUC, 0.85 [0.77–0.94]). The logistic regression model, combining clinical factors and AHI, was enhanced by the inclusion of AOPP and IL-6 (Chi-square = 25.06), and even further improved when GDF15 was added (Chi-square = 50.74). The integrated discrimination index increased by 0.06 to 0.16 when GDF15 was added to the models including clinical factors, AOPP, and IL-6. Conclusions: This study verified the independent and incremental value of GDF15 in identifying arteriosclerosis in OSA patients, surpassing clinical risk factors and other serum biomarkers such as AOPP and IL-6. [ABSTRACT FROM AUTHOR]

Background: The common carp (Cyprinus carpio) might best represent the domesticated allopolyploid animals. Although subgenome divergence which is well-known to be a key to allopolyploid domestication has been comprehensively characterized in common carps, the link between genetic architecture underlying agronomic traits and subgenome divergence is unknown in the selective breeding of common carps globally. Results: We utilized a comprehensive SNP dataset in 13 representative common carp strains worldwide to detect genome-wide genetic variations associated with scale reduction, vibrant skin color, and high growth rate in common carp domestication. We identified numerous novel candidate genes underlie the three agronomically most desirable traits in domesticated common carps, providing potential molecular targets for future genetic improvement in the selective breeding of common carps. We found that independently selective breeding of the same agronomic trait (e.g., fast growing) in common carp domestication could result from completely different genetic variations, indicating the potential advantage of allopolyploid in domestication. We observed that candidate genes associated with scale reduction, vibrant skin color, and/or high growth rate are repeatedly enriched in the immune system, suggesting that domestication of common carps was often accompanied by the disease resistance improvement. Conclusions: In common carp domestication, asymmetric subgenome selection is prevalent, while parallel subgenome selection occurs in selective breeding of common carps. This observation is not due to asymmetric gene retention/loss between subgenomes but might be better explained by reduced pleiotropy through transposable element-mediated expression divergence between ohnologs. Our results demonstrate that domestication benefits from polyploidy not only in plants but also in animals. [ABSTRACT FROM AUTHOR]

Background: Exposure to extreme cold or heat temperature is one leading cause of weather-associated mortality and morbidity in animals. Emerging studies demonstrate that the microbiota residing in guts act as an integral factor required to modulate host tolerance to cold or heat exposure, but common and unique patterns of animal-temperature associations between cold and heat have not been simultaneously examined. Therefore, we attempted to investigate the roles of gut microbiota in modulating tolerance to cold or heat exposure in mice., Results: The results showed that both cold and heat acutely change the body temperature of mice, but mice efficiently maintain their body temperature at conditions of chronic extreme temperatures. Mice adapt to extreme temperatures by adjusting body weight gain, food intake and energy harvest. Fascinatingly, 16 S rRNA sequencing shows that extreme temperatures result in a differential shift in the gut microbiota. Moreover, transplantation of the extreme-temperature microbiota is sufficient to enhance host tolerance to cold and heat, respectively. Metagenomic sequencing shows that the microbiota assists their hosts in resisting extreme temperatures through regulating the host insulin pathway., Conclusions: Our findings highlight that the microbiota is a key factor orchestrating the overall energy homeostasis under extreme temperatures, providing an insight into the interaction and coevolution of hosts and gut microbiota., (© 2024. The Author(s).)

Background: Prior to December 2022, there were no reports of reinfection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Shaanxi province, China. Since then, China has refined its strategy in response to coronaviruses. The purpose of this study was to determine the incidence of SARS-CoV-2 reinfections and its contributing factors, as well as to compare clinical characteristics between first and second episodes of infection in Shaanxi Province, China between December 2022 and February 2023., Methods: We conducted a cross-sectional study using an epidemiological survey system and electronic questionnaires to investigate the incidence of SARS-CoV-2 reinfection among previously infected individuals during the epidemic wave owing to the Omicron variant that began in December 2022. A logistic regression model was used to determine those factors influencing SARS-CoV-2 reinfections., Results: According to the virus variant that caused the first infection, the rate of reinfection for the Omicron variants was 1.28%, 1.96%, and 5.92% at 2-3 months, 4-5 months, and 7-9 months after the primary infection, respectively. The rate of reinfection for the Delta variants was 25.10% 11-12 months after the primary infection. Females, adults between 18 and 38 years and being a medical worker were associated with an increased risk of reinfection. Fever, cough, sore throat and fatigue were the four most common clinical symptoms during both first and second COVID-19 infections., Conclusions: In our study, the rate of SARS-CoV-2 reinfection increased over time during epidemic waves predominantly involving the Omicron variant in Shaanxi province, China. Large-scale infections are less likely in subsequent Omicron epidemic waves. Nevertheless, it is essential to continuously monitor cases of infection as well as continue surveillance for emerging SARS-CoV-2 variants., (© 2024. The Author(s).)