Polymerase-Based Signal Delay for Temporally Regulating DNA Involved Reactions, Programming Dynamic Molecular Systems, and Biomimetic Sensing.

Complex temporal molecular signals play a pivotal role in the intricate biological pathways of living organisms, and cells exhibit the ability to transmit and receive information by intricately managing the temporal dynamics of their signaling molecules. Although biomimetic molecular networks are successfully engineered outside of cells, the capacity to precisely manipulate temporal behaviors remains limited. In this study, the catalysis activity of isothermal DNA polymerase (DNAP) through combined use of molecular dynamics simulation analysis and fluorescence assays is first characterized. DNAP-driven delay in signal strand release ranged from 100 to 102 min, which is achieved through new strategies including the introduction of primer overhangs, utilization of inhibitory reagents, and alteration of DNA template lengths. The results provide a deeper insight into the underlying mechanisms of temporal control DNAP-mediated primer extension and DNA strand displacement reactions. Then, the regulated DNAP catalysis reactions are applied in temporal modulation of downstream DNA-involved reactions, the establishment of dynamic molecular signals, and the generation of barcodes for multiplexed detection of target genes. The utility of DNAP-based signal delay as a dynamic DNA nanotechnology extends beyond theoretical concepts and achieves practical applications in the fields of cell-free synthetic biology and bionic sensing.

FTO promotes gastric cancer progression by modulating MAP4K4 expression via demethylation in an m6A-dependent manner.

Gastric cancer (GC) is a serious malignant tumour with a high mortality rate and a poor prognosis. Recently, emerging evidence has suggested that N6-methyladenosine (m6A) modification plays a crucial regulatory role in cancer progression. However, the exact role of m6A regulatory factors FTO in GC is unclear. First, the expression of m6A methylation-related regulatory factors in clinical samples and the clinical data of the corresponding patients were obtained from The Cancer Genome Atlas (TCGA-STAD) dataset, and correlation analysis between FTO expression and patient clinicopathological parameters was subsequently performed. qRT-PCR, immunohistochemistry (IHC) and western blotting (WB) were used to verify FTO expression in GC. CCK-8, EdU, flow cytometry and transwell assays were used to evaluate the effect of FTO on the behaviour of GC cells. Transcriptome sequencing and RNA immunoprecipitation analysis were used to explore the potential regulatory mechanisms mediated by FTO. FTO was highly expressed in GC tissues and cells, and high expression of FTO predicted a worse prognosis than low expression. Functionally, overexpression of FTO promoted the proliferation, migration and invasion of GC cells but inhibited cell apoptosis. Mechanistically, we found that FTO is upregulated in GC and promotes GC progression by modulating the expression of MAP4K4. Taken together, our findings provide new insights into the effects of FTO-mediated m6A demethylation and could lead to the development of new strategies for GC monitoring and aggressive treatment.

The Inflammatory State of Follicular Fluid Combined with Negative Emotion Indicators can Predict Pregnancy Outcomes in Patients with PCOS.

Polycystic ovary syndrome (PCOS) is a complex endocrine disorder syndrome with an incidence of 6% to 10% in women of reproductive age. Women with PCOS not only exhibit abnormal follicular development and fertility disorders, but also have a greater tendency to develop anxiety and depression. Our aim was to evaluate the ability of inflammatory factors in follicular fluid to predict embryonic developmental potential and pregnancy outcome and to construct a machine learning model that can predict IVF pregnancy outcomes based on indicators such as basic sex hormones, embryonic morphology, the follicular microenvironment, and negative emotion. In this study, inflammatory factors (CRP, IL-6, and TNF-α) in follicular fluid samples obtained from 225 PCOS and 225 non-PCOS women were detected via ELISA. For patients with PCOS, the levels of CRP and IL-6 in the follicular fluid in the pregnant group were significantly lower than those in the nonpregnant group. For non-patients with PCOS, only the level of IL-6 in the follicular fluid was significantly lower in the pregnant group than in the nonpregnant group. In addition, for both PCOS and non-patients with PCOS, compared with those in the pregnant group, patients in the nonpregnant group showed more pronounced signs of anxiety and depression. Finally, the factors that were significantly different between the two subgroups (pregnancy and nonpregnancy) of patients with or without PCOS were identified by an independent sample t test first and further analysed by multilayer perceptron (MLP) and random forest (RF) models to distinguish the two clinical pregnancy outcomes according to the classification function. The accuracy of the RF model in predicting pregnancy outcomes in patients with or without PCOS was 95.6% and 91.1%, respectively. The RF model is more suitable than the MLP model for predicting pregnancy outcomes in IVF patients. This study not only identified inflammatory factors that can affect embryonic development and assessed the anxiety and depression tendencies of PCOS patients, but also constructed an AI model that predict pregnancy outcomes through machine learning methods, which is a beneficial clinical tool.

Research on Indoor Environment Prediction of Pig House Based on OTDBO-TCN-GRU Algorithm.

Temperature and humidity, along with concentrations of ammonia and hydrogen sulfide, are critical environmental factors that significantly influence the growth and health of pigs within porcine habitats. The ability to accurately predict these environmental variables in pig houses is pivotal, as it provides crucial decision-making support for the precise and targeted regulation of the internal environmental conditions. This approach ensures an optimal living environment, essential for the well-being and healthy development of the pigs. The existing methodologies for forecasting environmental factors in pig houses are currently hampered by issues of low predictive accuracy and significant fluctuations in environmental conditions. To address these challenges in this study, a hybrid model incorporating the improved dung beetle algorithm (DBO), temporal convolutional networks (TCNs), and gated recurrent units (GRUs) is proposed for the prediction and optimization of environmental factors in pig barns. The model enhances the global search capability of DBO by introducing the Osprey Eagle optimization algorithm (OOA). The hybrid model uses the optimization capability of DBO to initially fit the time-series data of environmental factors, and subsequently combines the long-term dependence capture capability of TCNs and the non-linear sequence processing capability of GRUs to accurately predict the residuals of the DBO fit. In the prediction of ammonia concentration, the OTDBO-TCN-GRU model shows excellent performance with mean absolute error (MAE), mean square error (MSE), and coefficient of determination (R2) of 0.0474, 0.0039, and 0.9871, respectively. Compared with the DBO-TCN-GRU model, OTDBO-TCN-GRU achieves significant reductions of 37.2% and 66.7% in MAE and MSE, respectively, while the R2 value is improved by 2.5%. Compared with the OOA model, the OTDBO-TCN-GRU achieved 48.7% and 74.2% reductions in the MAE and MSE metrics, respectively, while the R2 value improved by 3.6%. In addition, the improved OTDBO-TCN-GRU model has a prediction error of less than 0.3 mg/m3 for environmental gases compared with other algorithms, and has less influence on sudden environmental changes, which shows the robustness and adaptability of the model for environmental prediction. Therefore, the OTDBO-TCN-GRU model, as proposed in this study, optimizes the predictive performance of environmental factor time series and offers substantial decision support for environmental control in pig houses.

Photopolymerizable and Antibacterial Hydrogels Loaded with Metabolites from Lacticaseibacillus rhamnosus GG for Infected Wound Healing.

In response to increasing antibiotic resistance and the pressing demand for safer infected wound care, probiotics have emerged as promising bioactive agents. To address the challenges associated with the safe and efficient application of probiotics, this study successfully loaded metabolites from Lacticaseibacillus rhamnosus GG (LGG) into a gelatin cross-linked macromolecular network by an in situ blending and photopolymerization method. The obtained LM-GelMA possesses injectability and autonomous healing capabilities. Importantly, the incorporation of LGG metabolites endows LM-GelMA with excellent antibacterial properties against Staphylococcus aureus and Escherichia coli, while maintaining good biocompatibility. In vivo assessments revealed that LM-GelMA can accelerate wound healing by mitigating infections induced by pathogenic bacteria. This is accompanied by a reduction in the expression of key proinflammatory cytokines such as TNF-α, IL-6, VEGFR2, and TGF-ß, leading to increased re-epithelialization and collagen formation. Moreover, microbiological analysis confirmed that LM-GelMA can modulate the abundance of beneficial wound microbiota at family and genus levels. This study provides a facile strategy and insights into the functional design of hydrogels from the perspective of wound microenvironment regulation.

Retracted and republished from: "The current state of research on influenza antiviral drug development: drugs in clinical trial and licensed drugs".

Influenza viruses (IVs) threaten global human health due to the high morbidity, infection, and mortality rates. Currently, the influenza drugs recommended by the Food and Drug Administration are oseltamivir, zanamivir, peramivir, and baloxavir marboxil. These recommended antivirals are currently effective for major subtypes of IVs as the compounds target conserved domains in neuraminidase or polymerase acidic (PA) protein. However, this trend may gradually change due to the selection of antiviral drugs and the natural evolution of IVs. Therefore, there is an urgent need to develop drugs related to the treatment of influenza to deal with the next pandemic. Here, we summarized the cutting-edge research in mechanism of action, inhibitory activity, and clinical efficacy of drugs that have been approved and drugs that are still in clinical trials for influenza treatment. We hope this review will provide up-to-date and comprehensive information on influenza antivirals and generate hypotheses for screens and development of new broad-spectrum influenza drugs in the near future.

Migraines, vasomotor symptoms, and cardiovascular disease in the Coronary Artery Risk Development in Young Adults study.

OBJECTIVE: To examine whether vasomotor symptoms (VMS) and migraine headaches, hypothesized to be vasoactive conditions, are associated with greater risk for cardiovascular disease (CVD) events including strokes. METHODS: We performed a secondary data analysis of a subset of women (n = 1,954) in the Coronary Artery Risk Development in Young Adults (CARDIA) study, a population-based cohort, which began data collection at 18 to 30 y of age. We examined whether migraine headaches and VMS trajectories (characterized as minimal, increasing, and persistent) at CARDIA year 15 examination were associated with higher risk of CVD events and stroke (both ischemic and hemorrhagic) using Cox proportional hazards regression models and adjustment for traditional CVD risk factors (age, cigarette use, and levels of systolic and diastolic blood pressure, fasting glucose, high- and low-density cholesterol, and triglycerides) and reproductive factors. RESULTS: Among women with minimal VMS (n = 835), increasing VMS (n = 521), and persistent VMS (n = 598), there were 81 incident CVD events including 42 strokes. Women with histories of migraine and persistent VMS had greater risk of CVD (hazard ratio [HR], 2.25; 95% CI, 1.15-4.38) after adjustment for age, race, estrogen use, oophorectomy, and hysterectomy compared with women without migraine histories and with minimal/increasing VMS. After adjustment for CVD risk factors, these associations were attenuated (HR, 1.51; 95% CI, 0.73-3.10). Similarly, women with histories of migraine and persistent VMS had greater risk of stroke (HR, 3.15; 95% CI, 1.35-7.34), but these associations were attenuated after adjustment for CVD risk factors (HR, 1.70; 95% CI, 0.66-4.38). CONCLUSIONS: Migraines and persistent VMS jointly associate with greater risk for CVD and stroke, although risk is attenuated with adjustment for traditional CVD risk factors.

[Genetic analysis of eighteen patients from Gansu Province with Tetrahydrobiopterin deficiency].

OBJECTIVE: To explore the genetic basis of eighteen patients with Tetrahydrobiopterin deficiency (BH4D) from Gansu Province. METHODS: Eighteen patients diagnosed with BH4D at Gansu Provincial Maternal and Child Health Care Hospital from January 2018 to December 2021 were selected as the study subjects. Whole exome sequencing was carried out, and candidate variants were verified by Sanger sequencing. RESULTS: All of the thirty-six alleles of the eighteen patients were successfully determined by molecular genetic testing. Sixteen patients were found to harbor variants of the PTS gene, and two had harbored variants of the QDPR gene. Ten variants were detected in the PTS gene, with the most common ones being c.259C>T (34.38%) and c.286G>A (15.63%). Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.259C>T was classified as a pathogenic variant, whilst the c.286G>A, c.166G>A, c.200C>T, c.272A>G, c.402A>C, c.421G>T, c.84_291A>G and c.317C>T were classified as likely pathogenic variants. A novel c.289_290insCTT variant was classified as likely pathogenic (PM1+PM2_Supporting+PM3+PP3+PP4). The two variants (c.478C>T and c.665C>T) detected in the QDPR gene were both classified as variants of uncertain significance (PM1+PM2_Supporting+PP3+PP4). CONCLUSION: Genetic testing has clarified the pathogenic variants in these BH4D patients, which has enabled timely and accurate clinical intervention and treatment, and provided a reference for genetic counseling and reproductive guidance for their families.

Novel compound heterozygous variants in ARL13B lead to Joubert syndrome.

Joubert syndrome (JBTS) is a systematic developmental disorder mainly characterized by a pathognomonic mid-hindbrain malformation. All known JBTS-associated genes encode proteins involved in the function of antenna-like cellular organelle, primary cilium, which plays essential roles in cellular signal transduction and development. Here, we identified four unreported variants in ARL13B in two patients with the classical features of JBTS. ARL13B is a member of the Ras GTPase family and functions in ciliogenesis and cilia-related signaling. The two missense variants in ARL13B harbored the substitutions of amino acids at evolutionarily conserved positions. Using model cell lines, we found that the accumulations of the missense variants in cilia were impaired and the variants showed attenuated functions in ciliogenesis or the trafficking of INPP5E. Overall, these findings expanded the ARL13B pathogenetic variant spectrum of JBTS.

Prospective early adulthood risk factors for vasomotor symptoms in the Coronary Artery Risk Development in Young Adults study.

OBJECTIVE: Previous studies have assessed potential risk factors for vasomotor symptoms (VMS) beginning in midlife. We examined whether early adulthood risk factors predict VMS trajectories over time. METHODS: We performed a secondary data analysis of the Coronary Artery Risk Development in Young Adults (CARDIA) study, a population-based cohort. We included women who answered questions about VMS at three or more examinations (n = 1,966). We examined whether risk factors at baseline (when participants were aged 18-30 y; average age, 25 y) and the year 15 (Y15) exam (at ages 33-45 y; average age, 40 y) were associated with VMS trajectories from Y15 through Y35. Logistic regression models were used to evaluate the associations with VMS trajectories. RESULTS: We identified three trajectories of VMS presence: minimal (40%), increasing over time (27%), and persistent (33%). Baseline factors associated with persistent VMS over time included Black race, less than a high school education, depressive symptoms, migraines, cigarette use, and at Y15 hysterectomy. Baseline factors associated with increasing VMS over time included Black race and lower body mass index. Risk factors for bothersome VMS were similar and also included thyroid disease, although thyroid disease was not associated with persistence of VMS over time. Associations were similar among women who had not undergone hysterectomy and in Black and White women. CONCLUSIONS: Risk factors for VMS may be identified in early adulthood. Further examination of risk factors such as migraines and depressive symptoms in early adulthood may be helpful in identifying therapies for VMS.

A Gpr35-tuned gut microbe-brain metabolic axis regulates depressive-like behavior.

Gene-environment interactions shape behavior and susceptibility to depression. However, little is known about the signaling pathways integrating genetic and environmental inputs to impact neurobehavioral outcomes. We report that gut G-protein-coupled receptor, Gpr35, engages a microbe-to-brain metabolic pathway to modulate neuronal plasticity and depressive behavior in mice. Psychological stress decreases intestinal epithelial Gpr35, genetic deletion of which induces depressive-like behavior in a microbiome-dependent manner. Gpr35-/- mice and individuals with depression have increased Parabacteroides distasonis, and its colonization to wild-type mice induces depression. Gpr35-/- and Parabacteroides distasonis-colonized mice show reduced indole-3-carboxaldehyde (IAld) and increased indole-3-lactate (ILA), which are produced from opposing branches along the bacterial catabolic pathway of tryptophan. IAld and ILA counteractively modulate neuroplasticity in the nucleus accumbens, a brain region linked to depression. IAld supplementation produces anti-depressant effects in mice with stress or gut epithelial Gpr35 deficiency. Together, these findings elucidate a gut microbe-brain signaling mechanism that underlies susceptibility to depression.

Boosting Cu─In─Zn─S-based Quantum-Dot Light-Emitting Diodes Enabled by Engineering Cu─NiOx /PEDOT:PSS Bilayered Hole-Injection Layer.

The imbalance of charge injection is considered to be a major factor that limits the device performance of cadmium-free quantum-dot light-emitting diodes (QLEDs). In this work, high-performance cadmium-free Cu─In─Zn─S(CIZS)-based QLEDs are designed and fabricated through tailoring interfacial energy level alignment and improving the balance of charge injection. This is achieved by introducing a bilayered hole-injection layer (HIL) of Cu-doped NiOx (Cu─NiOx )/Poly(3,4-ethylenedioxythiophene): poly (styrene sulfonate) (PEDOT:PSS). High-quality Cu─NiOx film is prepared through a novel and straightforward sol-gel procedure. Multiple experimental characterizations and theoretical calculations show that the incorporation of Cu2+ ions can regulate the energy level structure of NiOx and enhance the hole mobility. The state-of-art CIZS-based QLEDs with Cu─NiOx /PEDOT:PSS bilayered HIL exhibit the maximum external quantum efficiency of 6.04% and half-life time of 48 min, which is 1.3 times and four times of the device with only PEDOT:PSS HIL. The work provides a new pathway for developing high-performance cadmium-free QLEDs.

Uncovering the hidden threat: The widespread presence of chromosome-borne accessory genetic elements and novel antibiotic resistance genetic environments in Aeromonas.

The emergence of antibiotic-resistant Aeromonas strains in clinical settings has presented an escalating burden on human and public health. The dissemination of antibiotic resistance in Aeromonas is predominantly facilitated by chromosome-borne accessory genetic elements, although the existing literature on this subject remains limited. Hence, the primary objective of this study is to comprehensively investigate the genomic characteristics of chromosome-borne accessory genetic elements in Aeromonas. Moreover, the study aims to uncover novel genetic environments associated with antibiotic resistance on these elements. Aeromonas were screened from nonduplicated strains collected from two tertiary hospitals in China. Complete sequencing and population genetics analysis were performed. BLAST analysis was employed to identify related elements. All newly identified elements were subjected to detailed sequence annotation, dissection, and comparison. We identified and newly designated 19 chromosomal elements, including 18 integrative and mobilizable elements (IMEs) that could be classified into four categories: Tn6737-related, Tn6836-related, Tn6840-related, and Tn6844a-related IMEs. Each class exhibited a distinct pattern in the types of resistance genes carried by the IMEs. Several novel antibiotic resistance genetic environments were uncovered in these elements. Notably, we report the first identification of the blaOXA-10 gene and blaVEB-1 gene in clinical A. veronii genome, the first presence of a tetA(E)-tetR(E) resistance gene environment within the backbone region in IMEs, and a new mcr-3.15 resistance gene environment. The implications of these findings are substantial, as they provide new insights into the evolution, structure, and dissemination of chromosomal-borne accessory elements.

Genomic epidemiology and heterogeneity of Providencia and their blaNDM-1-carrying plasmids.

Providencia as an opportunistic pathogen can cause serious infection, and moreover the emergence of multi-drug-resistant Providencia strains poses a potentially life-threatening risk to public health. However, a comprehensive genomic study to reveal the population structure and dissemination of Providencia is still lacking. In this study, we conducted a genomic epidemiology analysis on the 580 global sequenced Providencia isolates, including 257 ones sequenced in this study (42 ones were fully sequenced). We established a genome sequence-based species classification scheme for Providencia, redefining the conventional 11 Providencia species into seven genocomplexes that were further divided into 18 genospecies, providing an extensively updated reference for Providencia species discrimination based on the largest Providencia genome dataset to date. We then dissected the profile of antimicrobial resistance genes and the prevalence of multi-drug-resistant Providencia strains among these genocomplexes/genospecies, disclosing the presence of diverse and abundant antimicrobial resistance genes and high resistance ratios against multiple classes of drugs in Providencia. We further dissected the genetic basis for the spread of blaNDM-1 in Providencia. blaNDM-1 genes were mainly carried by five incompatible (Inc) groups of plasmids: IncC, IncW, IncpPROV114-NR, IncpCHS4.1-3, and IncpPrY2001, and the last three were newly designated in this study. By tracking the spread of blaNDM-1-carrying plasmids, IncC, IncpPROV114-NR, IncpCHS4.1-3, and IncpPrY2001 plasmids were found to be highly involved in parallel horizontal transfer or vertical clonal expansion of blaNDM-1 among Providencia. Overall, our study provided a comprehensive genomic view of species differentiation, antimicrobial resistance prevalence, and plasmid-mediated blaNDM-1 dissemination in Providencia.

Type 2 Diabetes Increases the Risk of Serious and Life-Threatening Conditions Among Adults With Traumatic Spinal Cord Injury.

Objective: To compare the incidence of and adjusted hazards for serious and life-threatening morbidities among adults with traumatic spinal cord injury (TSCI) with and without type 2 diabetes (T2D). Participants and Methods: A retrospective longitudinal cohort study was conducted from September 1, 2022 to February 2, 2023, among privately insured beneficiaries if they had an International Classification of Diseases, 9th Revision or 10th Revision, Clinical Modification diagnostic code for TSCI (n=9081). Incidence estimates of serious and life-threatening morbidities, and more common secondary and long-term health conditions, were compared at 5 years of enrollment. Survival models were used to quantify unadjusted and adjusted hazard ratios for serious and life-threatening morbidities. Results: Adults living with TSCI and T2D had a higher incidence of all of the morbidities assessed as compared with nondiabetic adults with TSCI. Fully adjusted survival models reported that adults with TSCI and T2D had a greater hazard for most of the serious and life-threatening conditions assessed, including sepsis (hazard ratio [HR]: 1.65), myocardial infarction (HR: 1.63), osteomyelitis (HR: 1.9), and stroke or transient ischemic attack (HR: 1.59). Rates for comorbid and secondary conditions were higher for individuals with TSCI and T2D, such as pressure sores, urinary tract infections, and depression, even after controlling for sociodemographic and comorbid conditions. Conclusion: Adults living with TSCI and T2D have a significantly higher incidence of and risk of developing serious and life-threatening morbidities as compared with nondiabetic adults with TSCI.

Association between the weight-adjusted waist index and stroke: a cross-sectional study.

BACKGROUND: The weight-adjusted waist index (WWI) is a new measure of obesity, and this study aimed to determine the association between the WWI and stroke. METHODS: Using the National Health and Nutrition Examination Survey (NHANES) 2011-2020 dataset, cross-sectional data from 23,389 participants were analysed. The correlation between the WWI and stroke was investigated through multivariate logistic regression and smoothing curve fitting. Subgroup analysis and interaction tests were also carried out. RESULTS: The research involved 23,389 participants, of whom 893 (3.82%) had a stroke. The fully adjusted model revealed a positive correlation between the WWI and stroke [1.25 (1.05, 1.48)]. Individuals who were in the highest quartile of WWI exhibited a 62% higher likelihood of experiencing a stroke than those in the lowest quartile [1.62 (1.06, 2.48)]. Subgroup analysis and interaction tests revealed that this positive correlation was similar in different population settings (all P for interaction > 0.05). CONCLUSION: A higher WWI was associated with a higher prevalence of stroke. The results of this study underscore the value of the WWI in stroke prevention and management.

The current state of research on influenza antiviral drug development: drugs in clinical trial and licensed drugs.

Influenza viruses (IVs) threaten global human health due to the high morbidity, infection, and mortality rates. Currently, the influenza drugs recommended by the FDA are oseltamivir, zanamivir, peramivir, and baloxavir marboxil. Notably, owing to the high variability of IVs, no drug exists that can effectively treat all types and subtypes of IVs. Moreover, the current trend of drug resistance is likely to continue as the viral genome is constantly mutating. Therefore, there is an urgent need to develop drugs related to the treatment of influenza to deal with the next pandemic. Here, we summarized the cutting-edge research in mechanism of action, inhibitory activity, and clinical efficacy of drugs that have been approved and drugs that are still in clinical trials for influenza treatment. We hope this review will provide up-to-date and comprehensive information on influenza antivirals and generate hypotheses for screens and development of new broad-spectrum influenza drugs in the near future.

Abundant diversity of accessory genetic elements and associated antimicrobial resistance genes in pseudomonas aeruginosa isolates from a single Chinese hospital.

OBJECTIVES: Pseudomonas aeruginosa has intrinsic antibiotic resistance and the strong ability to acquire additional resistance genes. However, a limited number of investigations provide detailed modular structure dissection and evolutionary analysis of accessory genetic elements (AGEs) and associated resistance genes (ARGs) in P. aeruginosa isolates. The objective of this study is to reveal the prevalence and transmission characteristics of ARGs by epidemiological investigation and bioinformatics analysis of AGEs of P. aeruginosa isolates taken from a Chinese hospital. METHODS: Draft-genome sequencing was conducted for P. aeruginosa clinical isolates (n = 48) collected from a single Chinese hospital between 2019 and 2021. The clones of P. aeruginosa isolates, type 3 secretion system (T3SS)-related virulotypes, and the resistance spectrum were identified using multilocus sequence typing (MLST), polymerase chain reaction (PCR), and antimicrobial susceptibility tests. In addition, 17 of the 48 isolates were fully sequenced. An extensive modular structure dissection and genetic comparison was applied to AGEs of the 17 sequenced P. aeruginosa isolates. RESULTS: From the draft-genome sequencing, 13 STs were identified, showing high genetic diversity. BLAST search and PCR detection of T3SS genes (exoT, exoY, exoS, and exoU) revealed that the exoS+/exoU- virulotype dominated. At least 69 kinds of acquired ARGs, involved in resistance to 10 different categories of antimicrobials, were identified in the 48 P. aeruginosa isolates. Detailed genetic dissection and sequence comparisons were applied to 25 AGEs from the 17 isolates, together with five additional prototype AGEs from GenBank. These 30 AGEs were classified into five groups -- integrative and conjugative elements (ICEs), unit transposons, IncpPBL16 plasmids, Incp60512-IMP plasmids, and IncpPA7790 plasmids. CONCLUSION: This study provides a broad-scale and deeper genomics understanding of P. aeruginosa isolates taken from a single Chinese hospital. The isolates collected are characterized by high genetic diversity, high virulence, and multiple drug resistance. The AGEs in P. aeruginosa chromosomes and plasmids, as important genetic platforms for the spread of ARGs, contribute to enhancing the adaptability of P. aeruginosa in hospital settings.

Factors associated with self-report of polycystic ovary syndrome in the Coronary Artery Risk Development in Young Adults study (CARDIA).

BACKGROUND: Polycystic ovary syndrome (PCOS) is underdiagnosed, but factors associated with women's report of diagnosis are not well-understood, particularly social determinants of health. Therefore, in a population-based cohort, we compared the characteristics of women with self-reported PCOS vs. women who have unrecognized PCOS vs. women without PCOS. METHODS: We performed a secondary data analysis of the Coronary Artery Risk Development in Young Adults (CARDIA) Study, a population-based, prospective cohort of Black and White women. Participants were women (n = 2028) who responded to the question, "Did a doctor or nurse ever tell you that you had polycystic ovarian syndrome or polycystic ovarian disease?" at the year 15 examination. Women who answered "yes" were defined as having self-reported PCOS. Women who answered "no or not sure" were defined as having unrecognized PCOS if they also had irregular menses and hyperandrogenemia between 20 and 30 years of age. Exposures of interest included social determinants of health, symptoms including irregular menses and hirsutism, and comorbid conditions. RESULTS: Forty-three (2.1%) of women had self-reported PCOS, 135 (6.7%) had unrecognized PCOS, and 1850 (91%) women were without PCOS. In logistic regression models adjusting for age, race, and center, women with self-reported PCOS were more likely to have obesity (OR 1.83, 95% CI 1.22, 2.75) and diabetes (OR 2.37, 95% CI 1.05, 5.33) compared to women without PCOS. Women with unrecognized PCOS were more likely to have hypertension (OR 1.68, 95% CI 1.03, 2.74) and food insecurity (OR 1.94, 95% CI 1.25, 3.01) compared to women without PCOS. CONCLUSIONS: Unrecognized PCOS is common. Self-report of PCOS is not associated with access to healthcare. Women who report PCOS are more often obese and comorbidities may contribute to recognition of PCOS.