Contribution of FOS in neutrophils to venous thromboembolism via miR-144 based on bioinformatic prediction and validation.

The Finkel-Biskis-Jinkins Osteosarcoma (c-Fos; encoded by FOS) plays an important role in several cardiovascular diseases, including atherosclerosis and stroke. However, the relationship between FOS and venous thromboembolism (VTE) remains unknown. We identified differentially expressed genes in Gene Expression Omnibus dataset, GSE48000, comprising VTE patients and healthy individuals, and analysed them using CIBERSORT and weighted co-expression network analysis (WGCNA). FOS and CD46 expressions were significantly downregulated (FOS p = 2.26E-05, CD64 p = 8.83E-05) and strongly linked to neutrophil activity in VTE. We used GSE19151 and performed PCR to confirm that FOS and CD46 had diagnostic potential for VTE; however, only FOS showed differential expression by PCR and ELISA in whole blood samples. Moreover, we found that hsa-miR-144 which regulates FOS expression was significantly upregulated in VTE. Furthermore, FOS expression was significantly downregulated in neutrophils of VTE patients (p = 0.03). RNA sequencing performed on whole blood samples of VTE patients showed that FOS exerted its effects in VTE via the leptin-mediated adipokine signalling pathway. Our results suggest that FOS and related genes or proteins can outperform traditional clinical markers and may be used as diagnostic biomarkers for VTE.

Hsa_circ_0004872 alleviates meningioma progression by sponging miR-190a-3p/PTEN signaling.

BACKGROUND: Meningioma, the most prevalent intracranial tumor, possesses a significant propensity for malignant transformation. Circular RNAs (circ-RNAs), a class of non-coding RNAs, have emerged as crucial players in tumorigenesis. This study explores the functional relevance of hsa_circ_0004872, a specific circ-RNA, in the context of meningioma. METHODS: Molecular structure and stability of hsa_circ_0004872 were elucidated through PCR identification. Meningioma cell proliferation and apoptosis were assessed using the CCK-8 assay and flow cytometry, respectively. Gene and protein expression were analyzed via qRT-PCR and western blot. Molecular interactions were confirmed through dual-luciferase reporter gene and RIP assays. RESULTS: Hsa_circ_0004872, derived from exons 2 to 4 of the host gene MAPK1, demonstrated enhanced stability compared to its host MAPK1. Clinical data described that hsa_circ_0004872 was reduced in meningioma tissues and cell lines, and negatively correlated to poor survival rate of meningioma patients. Overexpression of hsa_circ_0004872 exhibited inhibitory effects on cell proliferation and promotion of apoptosis in vitro. Subsequent investigations unveiled a direct interaction between hsa_circ_0004872 and miR-190a-3p, leading to the activation of the PI3K/AKT signaling pathway through targeting PTEN. Notably, miR-190a-3p silence accelerated the apoptosis and proliferation inhibition of meningioma cells by inactivating PTEN/PI3K/AKT signaling, while miR-190a-3p overexpression showed an opposite effect, which greatly reversed the anti-tumor effects of hsa_circ_0004872 overexpression. CONCLUSION: In summary, our findings highlighted the intricate role of hsa_circ_0004872 in meningioma, shedding light on the regulatory mechanisms involving circ-RNAs in tumor progression. This positions hsa_circ_0004872 as a potential key regulatory factor in meningioma with implications for future therapeutic interventions.

POSS and PEG Contained Copolymer for Antibioadhesive Rigid Contact Lenses Materials Application.

Myopia is a global public health issue. Rigid contact lenses (RCLs) are an effective way to correct or control myopia. However, bioadhesion issues remain one of the significant obstacles limiting its clinical application. Although enhancing hydrophilicity through various surface treatments can mitigate this problem, the duration of effectiveness is short-lived and the processing involved is complex and costly. Herein, an antiadhesive RCLs material was designed via 8-armed methacrylate-POSS (8MA-POSS), and poly(ethylene glycol) methacrylate (PEGMA) copolymerization with 3-[tris(trimethylsiloxy)silyl] propyl methacrylate (TRIS). The POSS and PEG segments incorporated P(TRIS-co-PEGMA-co-8MA-POSS) (PTPM) material was obtained and their optical transparency, refractive index, resolution, hardness, surface charge, thermal features, and wettability were tested and optimized. The antibioadhesion activities, including protein, lipid, and bacteria, were evaluated as well. In vitro and in vivo results indicated that the optimized antibioadhesive PTPM materials present good biocompatibility and biosafety. Thus, such POSS and PEG segments containing material were a potential antibioadhesive RCL material option.

Mechanical method to reduce aberrations for a two-sided coating axisymmetric optical lens based on the specialized finite element method.

Two-sided coated optical lenses are important in optical applications. A film-stress-induced aberration can adversely affect the lens performance. In this paper, a mechanical method has been developed to reduce this aberration. The proposed method uses a specialized finite element method with an easy modeling process and high versatility to analyze the impact of film parameters (including stress, the thickness, and the coating range) on aberrations under different lens geometric parameters. Theoretically, by selecting the property film parameters within the range of an application's requirements can reduce the aberrations. The proposed method could reduce film-stress-induced aberrations to make the aberration compensation easier.

[Research Advances in the Association Between Alzheimer's Disease and Double-Stranded RNA-Dependent Protein Kinase].

Alzheimer's disease (AD) is a severe threat to human health and one of the three major causes of human death.Double-stranded RNA-dependent protein kinase (PKR) is an interferon-induced protein kinase involved in innate immunity.In the occurrence and development of AD,PKR is upregulated and continuously activated.On the one hand,the activation of PKR triggers an integrated stress response in brain cells.On the other hand,it indirectly upregulates the expression of ß-site amyloid precursor protein cleaving enzyme 1 and facilitates the accumulation of amyloid-ß protein (Aß),which could activate PKR activator to further activate PKR,thus forming a sustained accumulation cycle of Aß.In addition,PKR can promote Tau phosphorylation,thereby reducing microtubule stability in nerve cells.Inflammation in brain tissue,neurotoxicity resulted from Aß accumulation,and disruption of microtubule stability led to the progression of AD and the declines of memory and cognitive function.Therefore,PKR is a key molecule in the development and progression of AD.Effective PKR detection can aid in the diagnosis and prediction of AD progression and provide opportunities for clinical treatment.The inhibitors targeting PKR are expected to control the activity of PKR,thereby controlling the progression of AD.Therefore,PKR could be a target for the development of therapeutic drugs for AD.

A novel camptothecin derivative, ZBH-01, exhibits superior antitumor efficacy than irinotecan by regulating the cell cycle.

BACKGROUND: Irinotecan (CPT-11) is a classic chemotherapeutic agent that plays an important role in the clinical treatment of metastatic colon cancer and other malignant tumors. We previously designed a series of novel irinotecan derivatives. In this study, we select one representative, ZBH-01, to investigate its sophisticated antitumor mechanism in colon tumor cells. METHODS: The cytotoxic activity of ZBH-01 on colon cancer cells was evaluate by MTT or Cell Counting Kit-8 (CCK8) assay, 3D and xenograft model. The inhibitory effect of ZBH-01 on TOP1 was detected by DNA relaxation assay and Immuno Complex of Ezyme (ICE) bioassay. The molecular mechanism of ZBH-01 was explored by Next-Generation Sequencing (NGS), bioinformatics analyses, flow cytometry, qRT-PCR, and western blot etc. RESULTS: ZBH-01 can induce obvious DNA damage and has superior antitumor activity against colon cancer cells compared to CPT-11 and SN38 (7-Ethyl-10-hydroxy camptothecin, the in vivo active form of CPT-11) both in vivo and in vitro. Its inhibitory effect on topoisomerase I (TOP1) was also comparable with these two control drugs. There are a much larger number of 842 downregulated and 927 upregulated mRNAs in ZBH-01 treatment group than that in the controls. The most significantly enriched KEGG pathways for these dysregulated mRNAs were DNA replication, the p53 signaling pathway, and the cell cycle. After constructing a protein-protein interaction (PPI) network and screening out a prominent cluster, 14 involved in the cell cycle process was identified. Consistently, ZBH-01 induced G0/G1 phase arrest in colon cancer cells, while CPT-11/SN38 caused S phase arrest. The initiation of apoptosis by ZBH-01 was also superior to CPT-11/SN38, followed by the increased expression of Bax, active caspase 3, and cleaved-PARP, and decreased expression of Bcl-2. Additionally, CCNA2 (cyclin A2), CDK2 (cyclin-dependent kinase 2), and MYBL2 (MYB proto-oncogene like 2) might be involved in the G0/G1 cell cycle arrest induced by ZBH-01. CONCLUSIONS: ZBH-01 can be an antitumor candidate drug for preclinical study in the future.

CRISPR/Cas12a-based assay for the rapid and high-sensitivity detection of Streptococcus agalactiae colonization in pregnant women with premature rupture of membrane.

BACKGROUND: Streptococcus agalactiae or group B Streptococcus (GBS) is a leading infectious cause of neonatal morbidity and mortality. It is essential to establish a robust method for the rapid and ultra-sensitive detection of GBS in pregnant women with premature rupture of membrane (PROM). METHODS: This study developed a CRISPR-GBS assay that combined the advantages of the recombinase polymerase amplification (RPA) and CRISPR/Cas12a system for GBS detection. The clinical performance of the CRISPR-GBS assay was assessed using vaginal or cervical swabs that were collected from 179 pregnant women with PROM, compared in parallel to culture-based matrix-assisted laser desorption ionization time-of-flight mass spectrometry (culture-MS) method and real-time quantitative polymerase chain reaction (qPCR) assay. RESULTS: The CRISPR-GBS assay can be completed within 35 min and the limit of detection was as low as 5 copies µL-1. Compared with the culture-MS, the CRISPR-GBS assay demonstrated a sensitivity of 96.64% (144/149, 95% confidence interval [CI] 92.39-98.56%) and a specificity of 100% (30/30, 95% CI 88.65-100%). It also had a high concordance rate of 98.88% with the qPCR assay. CONCLUSIONS: The established CRISPR-GBS platform can detect GBS in a rapid, accurate, easy-to-operate, and cost-efficient manner. It offered a promising tool for the intrapartum screening of GBS colonization.

The Application of Wearable Sensors and Machine Learning Algorithms in Rehabilitation Training: A Systematic Review.

The integration of wearable sensor technology and machine learning algorithms has significantly transformed the field of intelligent medical rehabilitation. These innovative technologies enable the collection of valuable movement, muscle, or nerve data during the rehabilitation process, empowering medical professionals to evaluate patient recovery and predict disease development more efficiently. This systematic review aims to study the application of wearable sensor technology and machine learning algorithms in different disease rehabilitation training programs, obtain the best sensors and algorithms that meet different disease rehabilitation conditions, and provide ideas for future research and development. A total of 1490 studies were retrieved from two databases, the Web of Science and IEEE Xplore, and finally 32 articles were selected. In this review, the selected papers employ different wearable sensors and machine learning algorithms to address different disease rehabilitation problems. Our analysis focuses on the types of wearable sensors employed, the application of machine learning algorithms, and the approach to rehabilitation training for different medical conditions. It summarizes the usage of different sensors and compares different machine learning algorithms. It can be observed that the combination of these two technologies can optimize the disease rehabilitation process and provide more possibilities for future home rehabilitation scenarios. Finally, the present limitations and suggestions for future developments are presented in the study.

Assessment System for Child Head Injury from Falls Based on Neural Network Learning.

Toddlers face serious health hazards if they fall from relatively high places at home during everyday activities and are not swiftly rescued. Still, few effective, precise, and exhaustive solutions exist for such a task. This research aims to create a real-time assessment system for head injury from falls. Two phases are involved in processing the framework: In phase I, the data of joints is obtained by processing surveillance video with Open Pose. The long short-term memory (LSTM) network and 3D transform model are then used to integrate key spots' frame space and time information. In phase II, the head acceleration is derived and inserted into the HIC value calculation, and a classification model is developed to assess the injury. We collected 200 RGB-captured daily films of 13- to 30-month-old toddlers playing near furniture edges, guardrails, and upside-down falls. Five hundred video clips extracted from these are divided in an 8:2 ratio into a training and validation set. We prepared an additional collection of 300 video clips (test set) of toddlers' daily falling at home from their parents to evaluate the framework's performance. The experimental findings revealed a classification accuracy of 96.67%. The feasibility of a real-time AI technique for assessing head injuries in falls through monitoring was proven.

Value of clinical features combined with multimodal ultrasound in predicting lymph node metastasis in cervical central area of papillary thyroid carcinoma.

OBJECTIVE: To explore the clinical features, multimodal ultrasound features and multimodal ultrasound imaging features in predicting lymph node metastasis in the central cervical region of papillary thyroid carcinoma. METHODS: A total of 129 patients with papillary thyroid carcinoma (PTC) confirmed by pathology were selected from our hospital from September 2020 to December 2022. According to the pathological results of cervical central lymph nodes, these patients were divided into metastatic group and non-metastatic group. Patients were randomly sampled and divided into training group (n = 90) and verification group (n = 39) according to the ratio of 7:3. The independent risk factors for central lymph node metastasis (CLNM) were determined by least absolute shrinkage and selection operator and multivariate logistic regression. Based on independent risk factors to build a prediction model, select the best diagnostic effectiveness of the prediction model sketch line chart, and finally, the line chart calibration and clinical benefits were evaluated. RESULTS: A total of 8, 11 and 17 features were selected from conventional ultrasound images, shear wave elastography (SWE) images and contrast-enhanced ultrasound (CEUS) images to construct the Radscore of conventional ultrasound, SWE and CEUS, respectively. After univariate and multivariate logistic regression analysis, male, multifocal, encapsulation, iso-high enhancement and multimodal ultrasound imaging score were independent risk factors for cervical CLNM in PTC patients (p < 0.05). Based on independent risk factors, a clinical combined with multimodal ultrasound feature model was constructed, and multimodal ultrasound Radscore were added to the clinical combined with multimodal ultrasound feature model to form a joint prediction model. In the training group, the diagnostic efficacy of combined model (AUC = 0.934) was better than that of clinical combined with multimodal ultrasound feature model (AUC = 0.841) and multimodal ultrasound radiomics model (AUC = 0.829). In training group and validation group, calibration curves show that the joint model has good predictive ability for cervical CLNM of PTC patients; The decision curve shows that most of the net benefits of the nematic chart are higher than those of clinical + multimodal ultrasound feature model and multimodal ultrasound radiomics model within a reasonable risk threshold range. CONCLUSION: Male, multifocal, capsular invasion and iso-high enhancement are independent risk factors of CLNM in PTC patients, and the clinical plus multimodal ultrasound model based on these four factors has good diagnostic efficiency. The joint prediction model after adding multimodal ultrasound Radscore to clinical and multimodal ultrasound features has the best diagnostic efficiency, high sensitivity and specificity, which is expected to provide objective basis for accurately formulating individualized treatment plans and evaluating prognosis.

Development and validation of a risk assessment scale for pathological scarring.

To develop a risk assessment scale for pathological scarring and validate its psychometric properties. This was a methodological study. Researchers developed the scale based on a literature review, qualitative study and Delphi expert consultation. Subsequently, 409 patients participated in the study to test the psychometric properties of the scale. We evaluated construct validity, content validity, internal consistency reliability, and interrater reliability. The researchers developed a scale consisting of three dimensions and 12 items. Factor analysis extracted a total of four common factors that accounted for 62.22% of the total variance. The results revealed that the item-content validity index (I-CVI) ranged from 0.67 to 1, while the scale-content validity index (S-CVI) was 0.82. Internal consistency reliability: Cronbach's α of the items ranged from 0.67 to 0.76, while Cronbach's α of the whole scale was 0.74. Interrater reliability: the Kappa number was 0.73. The final scale showed adequate construct validity, content validity, and reliability. It is appropriate for use in research and clinical practice settings to identify patients with a risk of pathological scarring. Further study is needed to confirm the scale's validity and reliability in other settings and populations.

A critical role of AMP-activated protein kinase in regulating intestinal nutrient absorption, barrier function, and intestinal diseases.

As one of the most important organs in animals, the intestine is responsible for nutrient absorption and acts as a barrier between the body and the environment. Intestinal physiology and function require the participation of energy. 5'-adenosine monophosphate-activated protein kinase (AMPK), a classical and highly expressed energy regulator in intestinal cells, regulates the process of nutrient absorption and barrier function and is also involved in the therapy of intestinal diseases. Studies have yielded findings that AMPK regulates the absorption of glucose, amino acids, and fatty acids in the intestine primarily by regulating transportation systems, as we detailed here. Moreover, AMPK is involved in the regulation of the intestinal mechanical barrier and immune barrier through manipulating the expression of tight junctions, antimicrobial peptides, and secretory immunoglobulins. In addition, AMPK also participates in the regulation of intestinal diseases, which indicates that AMPK is a promising therapeutic target for intestinal diseases and cancer. In this review, we summarized the current understanding regarding how AMPK regulates intestinal nutrient absorption, barrier function, and intestinal diseases.

Suboptimal immune recovery and associated factors among people living with HIV/AIDS on second-line antiretroviral therapy in central China: A retrospective cohort study.

The introduction and scale-up of antiretroviral therapy (ART) have contributed to significantly improved patients with acquired immune deficiency syndrome (AIDS) quality of life and prolongs their survival. This has occurred by suppressing viral replication and recovering the CD4 cell count. However, some patients do not normalize their CD4 cell count, despite suppression of the viral load (VL). Patients with suboptimal immune recovery (SIR), as defined by a VL < 400 copies/ml with a CD4 cell count of<200 cells/µl, after ART initiation, exhibit severe immune dysfunction and have a higher risk of AIDS and non-AIDS events. In recent years, People living with HIV/AIDS (PLWHA) with first-line ART failure began to gradually switch to second-line ART. This study aimed to examine the prevalence and factors affecting SIR among PLWHA who switch to second-line ART in rural China. A 1-year retrospective cohort study was conducted among PLWHA who switched to second-line ART between January 2009 and December 2018. All patients with a VL < 400 copies/ml after 1 year of second-line ART were included. SIR was defined as a CD4 cell count <200 cells/µl and a VL < 400 copies/ml after 1 year of second-line ART. The data collected from medical records were analyzed by univariate and multivariate analyses. A total of 5294 PLWHA met the inclusion criteria, 24 died, and 1152 were lost to follow-up after 1 year of second-line ART. Among 4118 PLWHA who were followed up, 3039 with a VL < 400 copies/ml had their data analyzed, and the prevalence of SIR was 13.1%. The patients' mean age at recruitment was 47.6 ± 8.1 years and 45.3% were men. A total of 30.7% of patients were HIV-positive for >8 years and 88.2% were receiving ART before starting second-line ART for >3 years. The mean CD4 cell count was 354.8 ± 238.2 cells/µl. A multivariable analysis showed that male sex, single status (unmarried or divorced), and a low CD4 cell count were risk factors for SIR among PLWHA with second-line ART. The prevalence of SIR among PLWHA who switched to second-line ART in this retrospective cohort study is lower than that in most other studies. Several factors associated with SIR include male sex, marital status, and CD4 cell count levels in PLWHA.

Prevotella as the hub of the cervicovaginal microbiota affects the occurrence of persistent human papillomavirus infection and cervical lesions in women of childbearing age via host NF-κB/C-myc.

There is evidence that coinfection of cervicovaginal high-risk human papillomavirus (HR-HPV) and bacteria is common in women of childbearing age. However, the relationship between bacterial vaginosis (BV) and persistent HR-HPV infection in women of childbearing age and the underlying mechanisms remain unclear. In this study, we determined whether BV affects persistent HR-HPV infection in women aged 20-45 years and explored the possible mechanisms of their interactions. From January 1 to April 30, 2020, we recruited women aged 20-45 years with and without BV at a ratio of 1:2 from Fujian Maternity and Child Health Hospital. All women were followed up at 0, 12, and 24 months. A BV assay, HR-HPV genotyping and cervical cytology were performed at each follow-up. At 0 months, additional vaginal secretions and cervical exfoliated cells were collected for 16S ribosomal RNA sequencing, bacterial metabolite determination, and POU5F1B, C-myc, TLR4, NF-κB, and hTERT quantification. A total of 920 women were included. The abundance of Prevotella (p = 0.016) and Gardnerella (p = 0.027) were higher, whereas the abundance of Lactobacillus was lower (p = 0.001) in women with persistent HR-HPV infection and high-grade squamous intraepithelial lesions (HSIL). The abundance of Prevotella (p = 0.025) and Gardnerella (p = 0.018) increased in the vaginas of women with persistent HPV16 infection, whereas only the abundance of Prevotella (p = 0.026) was increased in women with persistent HPV18 infection. The abundance of Prevotella in the vagina was significantly positively correlated with the expression levels of TLR4, NF-κB, C-myc, and hTERT in host cervical cells (p < 0.05). Our findings suggest that overgrowth of Prevotella in the vagina may influence the occurrence of persistent HR-HPV infection-related cervical lesions through host NF-κB and C-myc signaling.

Total Synthesis of Suberitines A-D Featuring Tunable Biomimetic Late-Stage Oxidative Dearomatization and Acetalization.

Aaptaminoids are a unique family of marine alkaloids bearing a benzo[de][1,6]-naphthyridine core. This work describes the first total synthesis of suberitines A-D (1-4), four typical dimeric natural aaptaminoids, employing a step-saving bidirectional strategy. Key methods applied in the total synthesis include a cationic cascade to construct the bis-isoquinoline(s) with Hendrickson reagent-mediated Friedel-Crafts-type cyclization and eliminative aromatization, and a Bronsted acid-promoted Vilsmeier cyclization to generate the naphthyridine(s). The conditionally tunable PIDA-mediated oxidative dearomatization and subsequent methanolysis or hydrolysis successfully served as a powerful biomimetic tool to elaborate the essential oxygenated functionalities of suberitines A-D (1-4) in proper solvent-combinations at the final stage of total synthesis. The biomimetic proposal employed in the late-stage redox interchanges of related natural products was eventually supported by the isolation of synthetic intermediate 23 a as a natural product from the same natural source. Biological screening revealed that five of the synthetic samples including two natural suberitines and three full-skeleton natural product-like intermediates exhibited low micromolar inhibitory activities against the growth of cancer cell line K562.

Energy deprivation-induced AMPK activation inhibits milk synthesis by targeting PrlR and PGC-1α.

BACKGROUND: The mammary gland is responsible for milk production and secretion, which is critical for neonatal health during lactation. Lactation efficiency is largely affected by energy status with unclear mechanism. RESULTS: In the current study, we found that synthesis of milk fat and protein was significantly inhibited under energy-deficient conditions, which is accompanied with AMP-activated protein kinase (AMPK) activation. Modulating the AMPK signaling pathway directly or indirectly affects the synthesis of milk fat and protein. Besides mammalian target of rapamycin complex 1 (mTORC1) signaling in the regulation of milk synthesis, we discovered that AMPK mainly regulates the synthesis of milk protein through prolactin signaling. Mechanistically, AMPK triggers the ubiquitination of prolactin receptor (PrlR) through regulating the activity of ß-transducin repeat-containing protein (ß-TrCP, an E3 ligase). Subsequently, PrlR is degraded by the endocytosis process of lysosomes, which further attenuates prolactin signaling. In addition, our results revealed that AMPK activation inhibits milk fat synthesis through decreasing and accelerating de novo synthesis and ß-oxidation of fatty acids, respectively. To be precise, AMPK activation inhibits rate limiting enzymes and transcriptional regulatory factors involved in de novo fatty acid synthesis and decreases the acetylation process of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) to strengthen the oxidation of fatty acids. CONCLUSIONS: Taken together, AMPK regulates the synthesis of milk not only depends on canonical mTORC1 signaling and key rate-limiting enzymes, but also through manipulating the degradation of PrlR and the acetylation of PGC-1α. Video Abstract.

Molecular Characteristics and Risk Factors of Bloodstream Infection Caused by Escherichia coli ST131 in Southeast China.

BACKGROUND: E. coli ST131 is the predominant lineage among extraintestinal pathogenic E. coli isolates worldwide and is an important pathogen associated with all kinds of human infections. The aim of this study was to investigate the prevalence and molecular characteristics of E. coli ST131 and non-ST131 isolates that cause bloodstream infections and evaluate the risk factors for E. coli ST131. METHODS: A total of 103 E. coli isolates associated with bloodstream infection were collected between August 2014 and August 2015 at a Chinese university hospital. The isolates were classified into ST131 and non-ST131 E. coli groups by multilocus sequence typing. Phylogenetic analysis, susceptibility testing, virulence genotyping, PCR-based O typing, and pulsed-field gel electrophoresis (PFGE) were performed, and the clinical features of patients in both groups were compared. RESULTS: Overall, 12 isolates (11.7%) were identified as ST131 isolates, including 10 O25b-ST131 (83.3%) and 2 O16-ST131 (16.7%) clones. All 103 E. coli isolates were divided into four phylogenetic groups: B2 was the predominant phylogenetic group (n = 39, 37.9%), and it was followed in descending order by D (n = 33, 32.0%), A (n = 20, 19.4%), and B1 (n = 11, 10.7%). Compared with the non-ST131 isolates, the E. coli ST131 isolates harbored more virulence factors and were associated with a significantly higher incidence of urinary tract infection (p = 0.040) and a significantly greater length of hospital stay (p = 0.045). According to PFGE analysis, the molecular features of the E. coli ST131 isolates were highly diverse, and there was no dominant clone. CONCLUSIONS: The ST131 isolates collected from Southeast China in this study exhibited strong virulence and multiple drug resistance, and the main serotype was O25b-ST131. Therefore, future studies should focus on O16-ST131 subclones in order to better understand the prognosis of patients with bloodstream infection caused by E. coli ST131.

Pathogenic Characteristics and Genomic Analysis of a Rare Serotype Salmonella enterica Serovar Moualine Isolated from the Blood.

BACKGROUND: Salmonella is composed of a wide variety of serovars that cause human self-limited gastrointestinal illnesses or invasive infections. Most of the Salmonella strains of clinical isolates belong to the A - F group. In December 2012, a case of invasive infection was caused by a rare Salmonella, Salmonella enterica serovar Moualine (S. Moualine), identified as 047 outside of groups A - F, which was easily missed or misreported. The goal is to ex-plore clinical symptoms and therapies of blood infection caused by S. Moualine and to provide theoretical basis and molecular level date for Salmonella research by analyzing pathogenic characteristics and genome information of S. Moualine. METHODS: The S. Moualine genome was sequenced using a PacBio RS II platform and Illumina HiSeq 4000 platform and analysis for serotyping serovars, ST types, the characterization of antibiotic resistance, virulence and phylogeny. RESULTS: The clinical symptoms were mainly irregular recurrent fever, lasting 1 - 3 weeks, with mild gastrointestinal symptoms. The genome size of S. Moualine was 4,611,151 bp, the serotype was 047 (+), Hy (+), H1,6 (+), and multilocus sequence typing analysis was ST3038. S. Moualine contains the majority of virulence genes. Interestingly, S. Moualine also harbors the rck and Typhi colonization factor (tcf) genes, which may play a role in invasive infection. S. Moualine encodes 17 Salmonella pathogenicity islands and is potentially dangerous to human health. Both phenotypic and genomic characterizations have demonstrated that S. Moualine generally showed low antimicrobial resistance potential. CONCLUSIONS: There were few reports on S. Moualine. According to clinical symptoms and genetic analysis, S. Moualine was predicted to be a highly virulent bacteria and was also potentially dangerous to health of humans. This study highlights that the transparency of global surveillance genomic data could accelerate the understanding of the virulence and antimicrobial resistance makeup of a previously unknown threat.

Ferroptosis Regulation by Nutrient Signalling.

Tremendous progress has been made in the field of ferroptosis since this regulated cell death process was first named in 2012. Ferroptosis is initiated upon redox imbalance and driven by excessive phospholipid peroxidation. Levels of multiple intracellular nutrients (iron, selenium, vitamin E and coenzyme Q10) are intimately related to the cellular antioxidant system and participate in the regulation of ferroptosis. Dietary intake of monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA) regulates ferroptosis by directly modifying the fatty acid composition in cell membranes. In addition, amino acids and glucose (energy stress) manipulate the ferroptosis pathway through the nutrient-sensitive kinases mechanistic target of rapamycin complex 1 (mTORC1) and AMP-activated protein kinase (AMPK). Understanding the molecular interaction between nutrient signals and ferroptosis sensors might help in the identification of the roles of ferroptosis in normal physiology and in the development of novel pharmacological targets for the treatment of ferroptosis-related diseases.

Structural Investigation of Aaptourinamine by a Novel Module-Assembly-Based Calculation.

Natural products have various and complicated structures, which is still a challenge for elucidating these compounds, especially for those lacking two-dimensional nuclear magnetic resonance (2D NMR) correlations mainly caused by high C/H ratios or proton-deficient and multiple heteroatoms through the conventional structural analytical methods. We reported a novel module-assembly calculation method named Dooerafa, which included constructing the meta-structures by a grafting method based on the crucial and the limited 2D NMR correlations, ring-contraction strategy based on mechanic force field and quantum chemical theory, and self-assemble calculation in Python programming for shaping up the structural candidates along with DFT-GIAO calculation. This new method, verified by a known alkaloid spiroreticulatine with the structure determined by X-ray diffraction, was performed for the structural elucidation of aaptourinamine isolated from marine sponge Aaptos suberitoides, showing us a brand new scaffold of imidazo [4,5,1-ij]pyrrolo [3,2-f]quinolin-7(8H)-one, which has a biosynthetic relationship with the bioactive and structurally unique aaptamine alkaloid.