Search

Background: The variations in non-coding RNA alterations and the host immune response between patients with bacterial and non-bacterial sepsis, along with their clinical characteristics, are largely unknown. Methods: The landscape of long non-coding RNA (lncRNA) and mRNA in whole blood cells from pediatric patients with bacterial sepsis or non-bacterial sepsis were characterized using an Arraystar human LncRNA microarray. Weighted correlation network analysis (WGCNA) were conducted to identify immune-related LncRNA-mRNA signatures. Least absolute shrinkage and selection operator (Lasso) regression and Ridge regression analysis were employed to develop a specific LncRNA-mRNA signature, serving as a discriminant classifier for bacterial and non-bacterial sepsis in children. Results: A total of 33 differentially expressed lncRNAs and 52 mRNAs were identified in pediatric patients with either bacterial sepsis or non-bacterial sepsis. Among these, 69 lncRNAs and mRNAs were pinpointed using WGCNA and found to be significantly correlated with clinical parameters. Further intersection analysis identified 12 lncRNAs and 16 mRNAs as immune-related signature for discerning bacterial infections in children with sepsis. Additionaly, the lncRNA-mRNA co-expression network highlighted the key lncRNAs (AC090159.1 and AC080129.2) and mRNAs (S100A8 and TCF7L2) as an infection score model. Lasso regression analysis revealed that this infection score model achieved an area under the received operating curve (AUROC) of 0.96 in the training set and 0.86 in the validation set. Ultimately, the expression levels of these 4 key lncRNAs and mRNAs showed significant correlation with CRP or PCT levels. Conclusion: The machine learning model, developed utilizing key lncRNAs (AC090159.1 and AC080129.2) and mRNAs (S100A8 and TCF7L2), demonstrates robust discrimination and calibration capabilities for distinguishing between bacterial and non-bacterial sepsis in children.

Abstract The upper tropospheric water vapor is a key component of Earth's climate. Understanding variations in upper tropospheric water vapor and identifying its influencing factors is crucial for enhancing our comprehension of global climate change. While many studies have shown the impact of El Niño-Southern Oscillation (ENSO) and global warming on water vapor, how they affect the upper tropospheric water vapor remains unclear. Long-term, high-precision ERA5 specific humidity data from the European Centre for Medium-Range Weather Forecasts (ECMWF) provided the data foundation for this study. On this basis, we successfully obtained the patterns of global warming (Independent Component 1, IC1) and ENSO (Independent Component 2, IC2) by employing the strategy of independent component analysis (ICA) combined with non-parametric optimal dimension selection to investigate the upper tropospheric water vapor variations and responses to ENSO and global warming. The results indicate that global warming and ENSO are the primary factors contributing to water vapor variations in the upper troposphere, achieving the significant correlations of 0.87 and 0.61 with water vapor anomalies respectively. Together, they account for 86% of the global interannual variations in water vapor. Consistent with previous studies, our findings also find positive anomalies in upper tropospheric water vapor during El Niño years and negative anomalies during La Niña years. Moreover, the influence extent of ENSO on upper tropospheric water vapor varies with the changing seasons.

Abstract Background Hyperemesis gravidarum (HG) is a severe form of pregnancy-related nausea and vomiting affecting 0.3–2.3% of pregnancies, which can lead to fluid, electrolyte, and acid–base imbalances, nutritional deficiencies, and weight loss, and is usually severe enough to require hospitalization. Abnormally elevated urinary ketones are commonly seen in patients with HG, and ketone bodies are free to pass through the placenta, and maternal hyperketonemia, with or without acidosis, is associated with an increased rate of stillbirth, an increased incidence of congenital anomalies, and impaired neurophysiologic development of the infant. This study investigates the obstetric outcomes of patients with HG and whether HG increases the incidence of cardiovascular disease in the offspring. Methods This study included 1020 pregnant women who were hospitalized in our hospital for HG and ultimately delivered in our hospital as well as pregnant women without HG in early gestation and delivered in our hospital from January 2019-January 2020, and we collected and followed up the clinical information of the pregnant women and their offspring. Results Pregnant women with HG were more likely to have severe urinary ketones, the rate of early miscarriage and mid-term miscarriage was significantly higher in women with HG compared to pregnant women without HG. Fetal and neonatal head and abdominal circumferences were smaller in HG group than in control group. Neonatal birth weight and length were also lower in the HG group and cardiovascular anomalies were more likely to occur in the offspring of women with HG when all births were followed up for 3 years. Conclusions HG may cause poor obstetric outcomes and was associated with the development of cardiovascular disease in the offspring of women with HG.

Background: Telomere shortening is strongly associated with cardiovascular aging and disease, and patients with shorter telomeres in peripheral blood leukocytes are at higher risk of cardiovascular diseases such as heart failure and atrial fibrillation (AF). Telomerase reverse transcriptase (TERT) maintains telomere length, and overexpression of TERT has been shown to reduce cardiomyocyte apoptosis and myocardial infarct size, and extend the lifespan of aged mice. However, the specific impact of TERT on the electrophysiology of cardiomyocytes remains to be elucidated. The aims of this study were to evaluate the role of TERT in Ca2+ homeostasis and mitochondrial function in atrial myocytes as well as the underlying mechanisms. Methods: TERT overexpressed and silenced HL-1 cells were constructed with lentiviruses, and the respective empty lentiviral vectors were used as negative controls. Then the patch clamp technique was used to record the electrophysiological characteristics such as cell action potential duration (APD) and L-type Ca2+ currents (ICa,L), flow cytometry was used to detect intracellular Ca2+ concentration and mitochondrial membrane potential (MMP), and the Seahorse assay was used to measure the oxygen consumption rate (OCR). Results: TERT silencing led to intracellular Ca2+ overload, shortened APD, decreased ICa,L current density, altered Ca2+ gating mechanism, decreased MMP and OCR, and increased reactive oxygen species (ROS), whereas TERT overexpression led to the reverse effects. Additionally, TERT silencing resulted in intracellular Ca2+ overload with decreased expression of the SERCA2a, CaV1.2, and NCX1.1, whereas TERT overexpression had opposing effects. Furthermore, we discovered that TERT could regulate the expression of p53 and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). The expression of PGC-1α was downregulated by the p53 agonist Tenovin-6 but upregulated by the p53 inhibitor PFTα. The effects of the PGC-1α inhibitor SR-18292 on intracellular Ca2+ and cell electrophysiology were similar to those of silencing TERT, whereas the PGC-1α agonist ZLN005 produced comparable outcomes to TERT overexpression. Conclusions: TERT silencing-induced Ca2+ overload and mitochondrial dysfunction may be one mechanism of age-related AF. Overexpression of TERT reduced the basis for arrhythmia formation such as AF, suggesting a favorable safety profile for TERT therapy. TERT regulated intracellular Ca2+ homeostasis and mitochondrial function through the p53/PGC-1α pathway. In addition, PGC-1α might be a novel target for AF, suggesting that intervention for AF should be not limited to abnormal cation handling.

Abstract Background Hemorrhage is a potential and serious adverse drug reaction, especially for geriatric patients with long-term administration of rivaroxaban. It is essential to establish an effective model for predicting bleeding events, which could improve the safety of rivaroxaban use in clinical practice. Methods The hemorrhage information of 798 geriatric patients (over the age of 70 years) who needed long-term administration of rivaroxaban for anticoagulation therapy was constantly tracked and recorded through a well-established clinical follow-up system. Relying on the 27 collected clinical indicators of these patients, conventional logistic regression analysis, random forest and XGBoost-based machine learning approaches were applied to analyze the hemorrhagic risk factors and establish the corresponding prediction models. Furthermore, the performance of the models was tested and compared by the area under curve (AUC) of the receiver operating characteristic (ROC) curve. Results A total of 112 patients (14.0%) had bleeding adverse events after treatment with rivaroxaban for more than 3 months. Among them, 96 patients had gastrointestinal and intracranial hemorrhage during treatment, which accounted for 83.18% of the total hemorrhagic events. The logistic regression, random forest and XGBoost models were established with AUCs of 0.679, 0.672 and 0.776, respectively. The XGBoost model showed the best predictive performance in terms of discrimination, accuracy and calibration among all the models. Conclusion An XGBoost-based model with good discrimination and accuracy was built to predict the hemorrhage risk of rivaroxaban, which will facilitate individualized treatment for geriatric patients.

BackgroundAtrial fibrillation (AF) is the most common cardiac arrhythmia and significantly increases the risk of stroke and heart failure (HF), contributing to a higher mortality rate. Increasing age is a major risk factor for AF; however, the mechanisms of how aging contributes to the occurrence and progression of AF remain unclear. This study conducted weighted gene co-expression network analysis (WGCNA) to identify key modules and hub genes and determine their potential associations with aging-related AF.Materials and methodsWGCNA was performed using the AF dataset GSE2240 obtained from the Gene Expression Omnibus, which contained data from atrial myocardium in cardiac patients with permanent AF or sinus rhythm (SR). Hub genes were identified in clinical samples. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were also performed.ResultsGreen and pink were the most critical modules associated with AF, from which nine hub genes, PTGDS, COLQ, ASTN2, VASH1, RCAN1, AMIGO2, RBP1, MFAP4, and ALDH1A1, were hypothesized to play key roles in the AF pathophysiology in elderly and seven of them have high diagnostic value. Functional enrichment analysis demonstrated that the green module was associated with the calcium, cyclic adenosine monophosphate (cAMP), and peroxisome proliferator-activated receptors (PPAR) signaling pathways, and the pink module may be associated with the transforming growth factor beta (TGF-β) signaling pathway in myocardial fibrosis.ConclusionWe identified nine genes that may play crucial roles in the pathophysiological mechanism of aging-related AF, among which six genes were associated with AF for the first time. This study provided novel insights into the impact of aging on the occurrence and progression of AF, and identified biomarkers and potential therapeutic targets for AF.

ABSTRACT Rapid increase in resistance of Helicobacter pylori (H. pylori) has hindered antibiotics-based eradication efforts worldwide and raises the need for additional approaches. Here, we investigate the role of zinc-based compounds in inhibiting H. pylori growth and modulating antibiotic sensitivities, interrogate their downstream transcriptomic changes, and highlight the potential mechanism driving the observed effects. We showed that zinc acetate inhibited H. pylori growth and increased H. pylori sensitivity to levofloxacin. Transcriptomic profiling showed distinct gene expression patterns between zinc acetate treated groups versus controls. In particular, we independently replicated the association between zinc acetate treatment and increased ssrA expression. Knockdown of ssrA restored levofloxacin resistance to levels of the control group. In this study, we first demonstrated the role of zinc acetate in H. pylori growth and antibiotic sensitivities. Additionally, we explored the transcriptomic perturbations of zinc acetate followed by functional knockdown follow-up of differentially expressed ssrA, highlighting the role of tmRNA and trans-translation in H. pylori levofloxacin resistance. Our results provide alternative and complementary strategies for H. pylori treatment and shed light on the underlying mechanisms driving these effects. IMPORTANCE Helicobacter pylori (H. pylori) eradication plays an important role in gastric cancer prevention, but the antimicrobial resistance of H. pylori is fast becoming a growing concern. In this study, we investigated the role of zinc acetate in inhibiting H. pylori growth and modulating antibiotic sensitivities in vitro. Additionally, we explored the transcriptomic perturbations of zinc acetate followed by functional knockdown follow-up of differentially expressed ssrA, highlighting the role of tmRNA and trans-translation in H. pylori levofloxacin resistance. Our results open up a new horizon for the treatment of antibiotic-resistant H. pylori.

Jiao Fan, Yige Ding, et al. examine the impact of cytosine and adenine deaminases on transcriptome-wide gene expression and splicing in HeLa and HEK293T cells. They found that both kinds of editors could induce broad changes in expression and splicing, independent of Cas9 activity, highlighting the need for further efforts to characterize deaminase enzymes in base editor platforms.

Until now, the transcriptome of preimplantation mouse embryos has only been analysed by short-read sequencing. Here, the authors perform long-read sequencing to provide a more detailed transcriptome of the preimplantation mouse embryo, identifying various novel transcripts, for example Kdm4dl.

Renin-angiotensin system (RAS) inhibitors and calcium channel blockers (CCB) are often used together in chronic kidney disease (CKD). The PubMed, EMBASE, and Cochrane Library databases were searched to identify randomized controlled trials (RCTs) in order to explore better subtypes of CCB for the treatment of CKD. This meta-analysis of 12 RCTs with 967 CKD patients who were treated with RAS inhibitors demonstrated that, when compared with L-type CCB, N-/T-type CCB was superior in reducing urine albumin/protein excretion (SMD, −0.41; 95% CI, −0.64 to −0.18; p < 0.001) and aldosterone, without influencing serum creatinine (WMD, −3.64; 95% CI, −11.63 to 4.35; p = 0.37), glomerular filtration rate (SMD, 0.06; 95% CI, −0.13 to 0.25; p = 0.53), and adverse effects (RR, 0.95; 95% CI, 0.35 to 2.58; p = 0.93). In addition, N-/T-type CCB did not decrease the systolic blood pressure (BP) (WMD, 0.17; 95% CI, −1.05 to 1.39; p = 0.79) or diastolic BP (WMD, 0.64; 95% CI, −0.55 to 1.83; p = 0.29) when compared with L-type CCB. In CKD patients treated with RAS inhibitors, N-/T-type CCB is more effective than L-type CCB in reducing urine albumin/protein excretion without increased serum creatinine, decreased glomerular filtration rate, and increased adverse effects. The additional benefit is independent of BP and may be associated with decreased aldosterone (PROSPERO, CRD42020197560).

In atherosclerotic plaques, transformation of macrophages into foam cells is a key step in initiating the inflammatory response. Here Fan et al. show that casein kinase 2-interacting protein-1 (CKIP-1) limits foam cell formation and atherosclerosis by preventing expression of the scavenger receptor LOX-1 through REGγ-mediated degradation of Oct-1.

The dynamic emissivity retrieved from window channels of the microwave humidity sounder II (MWHS-2) onboard the China Meteorological Administration’s FengYun (FY)-3C polar orbiting satellite can provide more realistic emissivity over lands and potentially improve the numerical weather prediction (NWP) forecasts. However, whether the assimilation with the dynamic emissivity works for the precipitation forecasts over the complex geography is less investigated. In this paper, a typical precipitating case generated by the Southwest Vortex is selected and the Weather Research and Forecasting data assimilation (WRFDA) system is applied to examine the impacts of assimilating MWHS-2/FY-3C with the uses of the emissivity atlas and the dynamic emissivity on the forecasts. The results indicate that the use of the dynamic emissivity retrieved from the 89 GHz channel of MWHS-2/FY-3C apparently increases the used data number for assimilation and does improve the initial fields and the 24-hour forecasts (from 0000 UTC 24 June 2016 to 0000 UTC 25 June 2016) of precipitation distribution and intensity except for the rainfall over 100 mm. But these positive impacts are not evidently better than those with the emissivity atlas. In general, these results still suggest that the future use of the dynamic emissivity in the assimilation over the complex terrain is promising.

Anticentromere antibodies (ACA) were associated with lower oocyte maturation rates and cleavage rates, while the mechanism was not clear. Aims of this study were to examine whether active immunization with centromere protein C could elicit the CENP-C autoantibody in mice and the impacts of the CENP-C autoantibody on oocyte meiosis. Mice were divided into two groups, one was the experimental group immunized with human centromere protein C and Freund’s adjuvant (CFA), and the other was the control group injected with CFA only. Serum and oocytes of BALB/c mice immunized with human centromere protein C (CENP-C) in complete Freund’s adjuvant (CFA) or injected with only CFA were studied for the development of the CENP-C antibody. Rates of germinal vesicle breakdown (GVBD), first polar body (Pb1) extrusion, abnormal spindle morphology, and chromosome misalignment were compared between the experimental group and the control group. The CENP-C antibody was only observed in serum and oocytes of mice immunized with the centromere protein C antigen. The first polar body (Pb1) extrusion rate was lower in the experimental group (P

A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-22148-6

Our purpose is to explore whether anti-dsDNA antibody, which was demonstrated to enter living cells and induced apoptosis, could adversely affect reproductive outcomes. A total of 259 women receiving the in vitro fertilization-embryo transfer (IVF) cycle were enrolled in this study, including 52 women with positive ANA and anti-dsDNA (ANA+/anti-dsDNA+ group), 86 women with positive ANA and negative anti-dsDNA (ANA+/anti-dsDNA− group), and 121 women with negative ANA and anti-dsDNA (ANA−/anti-dsDNA− group). 136 nonpregnant women among 259 patients in the IVF-ET cycle were enrolled in the hormone replacement therapy frozen-thawed embryo transfer (HRT-TET) cycle. We compared basic characters and IVF outcomes among three groups in fresh embryo transfer and frozen-thawed embryo transfer cycle, respectively. The number of retrieved oocytes, available embryos, and high-quality embryos in the ANA+/anti-dsDNA+ group was lower than those in the other two groups in the fresh embryo transfer cycle. The rates of fertilization, implantation, and clinical pregnancy in the ANA+/anti-dsDNA+ group were the lowest, while the early miscarriage rate was the highest in the ANA+/anti-dsDNA+ group both in the fresh embryo transfer cycle and in the frozen-thawed embryo transfer cycle. Our data suggested that anti-dsDNA antibody may be the essential marker for defective oocytes or embryos in infertile women with any type of ANA.

Highlights: A flow-bed water purification system with an asymmetric solar-thermal and catalytic membrane is designed for synergistic solar-thermal desalination of seawater/brine and catalytic degradation of organic pollutants. The hydrogen bonding networks can be regulated by the abundant surface –OH groups and the in situ generated ions and radicals during the degradation process for promoting solar-driven steam generation. The de-solvation of solvated Na+ and subsequent nucleation/growth of NaCl are effectively inhibited by SO42−/HSO5− ions. Although solar steam generation strategy is efficient in desalinating seawater, it is still challenging to achieve continuous solar-thermal desalination of seawater and catalytic degradation of organic pollutants. Herein, dynamic regulations of hydrogen bonding networks and solvation structures are realized by designing an asymmetric bilayer membrane consisting of a bacterial cellulose/carbon nanotube/Co2(OH)2CO3 nanorod top layer and a bacterial cellulose/Co2(OH)2CO3 nanorod (BCH) bottom layer. Crucially, the hydrogen bonding networks inside the membrane can be tuned by the rich surface –OH groups of the bacterial cellulose and Co2(OH)2CO3 as well as the ions and radicals in situ generated during the catalysis process. Moreover, both SO42− and HSO5− can regulate the solvation structure of Na+ and be adsorbed more preferentially on the evaporation surface than Cl−, thus hindering the de-solvation of the solvated Na+ and subsequent nucleation/growth of NaCl. Furthermore, the heat generated by the solar-thermal energy conversion can accelerate the reaction kinetics and enhance the catalytic degradation efficiency. This work provides a flow-bed water purification system with an asymmetric solar-thermal and catalytic membrane for synergistic solar thermal desalination of seawater/brine and catalytic degradation of organic pollutants. [ABSTRACT FROM AUTHOR]

Solar‐driven steam generation has emerged as a sustainable technology for addressing freshwater scarcity. However, significant challenges still exist in developing high‐performance, multifunctional evaporators that are adept at both efficiently evaporating water and degrading pollutants, primarily because of the trade‐offs among functional designs. Here, a self‐floating solar evaporator is reported by functionalizing balsa wood with solar‐thermal conversion material carbon nanotubes and catalytic manganese dioxide (MnO2) nanoflowers for simultaneous solar evaporation and pollutant degradation. MnO2 nanoflowers are rich in oxygen vacancies that can effectively activate peroxymonosulfate to generate reactive oxygen species for efficient organic pollutant degradation. A distinctive non‐wetted porous interior structure and a precisely targeted water pathway are spontaneously established in the multifunctional evaporator, ensuring fast water supply, thermal insulation, efficient mass transfer, and high buoyancy. The resulting evaporators successfully combine an impressive evaporation rate of 2.74 kg m−2 h−1, a high pollutant degradation efficiency (98.3% for 100 mg L−1 tetracycline and 97.4% for 200 mg L−1 Methyl orange), and stable self‐floating and self‐standing capabilities that ensure long‐term operation stability even in complex real‐world environments. This work provides an approach to design multifunctional solar evaporators, ensuring strong alignment with practical requirements while expanding their potential application scenarios. [ABSTRACT FROM AUTHOR]

SiC-coated C/C composites with mechanical damage were repaired by the heat treatment method and slurry painting–preoxidation. The effects of different process parameters on the microstructure, interface bonding and oxidation resistance of Si-SiC repair coatings at 1773 K for 10 h were studied. The results show that the repair coating is tightly bonded to the original coating and the C/C substrate, and there is no obvious interface. Under the optimal parameters, the weight reduction in the repaired specimen merely amounted to 0.32% subsequent to oxidation at 1773 K for 10 h, and the mass loss was 74.79% lower than that of the damaged specimen, being proximate to that of the intact specimen. The objective of this work lies in achieving a greater density of the coating within the repair zone by manipulating the diverse powder ratios and preoxidation temperatures in the repair slurry, thereby safeguarding the C/C composite material against oxidation during its service. It offers a convenient and highly efficient approach for the repair of coatings with substantial size defects, significantly prolonging the service life of the material. [ABSTRACT FROM AUTHOR]