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Abstract Background This paper investigated the link between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and diabetic kidney disease (DKD) in adult diabetic patients and identified the optimal NHHR value for impacting DKD. Methods This cross-sectional research made use of records from the National Health and Nutrition Examination Survey (NHANES) executed between 2005 and 2016. The link of NHHR to DKD risk was analyzed by logistic regression and restricted cubic spline (RCS) models. The stability and reliability of the results were assessed by subgroup analysis and sensitivity analysis. Results In total, 4,177 participants were involved. As a continuous variable, NHHR was markedly connected to an increased risk of DKD (OR 1.07, 95% CI 1.02, 1.12, P

A new measure for intuitionistic fuzzy numbers (IFNs) is proposed to reflect the magnitude of IFNs, and a novel ranking approach for IFNs is presented based on this measure. Furthermore, the theoretical basis of the ranking method is investigated, and several intuitionistic fuzzy monotonic dependent ordered weighted averaging (IFMDOWA) operators are developed, such as the conservative IFMDOWA (COV-IFMDOWA) operator, positive intuitionistic fuzzy monotonic DOWA (POS-IFMDOWA) operator, conservative intuitionistic fuzzy hybrid monotonic dependent order weighted averaging (COV-IFHMDOWA) operator, and positive intuitionistic fuzzy hybrid monotonic dependent order weighted averaging (POS-IFHMDOWA) operator. Finally, a numerical example is given to illustrate the flexibility of our proposed monotonic dependent order weighted averaging operators in a practical decision making process.

During ovarian development, gonadal ridge epithelial-like (GREL) cells arise from the epithelial cells of the ventral surface of the mesonephros. They ultimately develop into follicular granulosa cells or into ovarian surface epithelial cells. Stromal fibroblasts arise from the mesonephros and penetrate the ovary. We developed methods for isolating and culturing fetal ovarian GREL cells and ovarian fibroblasts by expansion of colonies without passage. In culture, these two cell types were morphologically different. We examined the expression profile of 34 genes by qRT-PCR, of which 24 genes had previously been studied in whole fetal ovaries. Expression of nine of the 10 newly-examined genes in fetal ovaries correlated with gestational age (MUC1, PKP2, CCNE1 and CCNE2 negatively; STAR, COL4A1, GJA1, LAMB2 and HSD17B1 positively). Comparison between GREL cells and fetal fibroblasts revealed higher expression of KRT19, PKP2, OCLN, MUC1, ESR1 and LGR5 and lower expression of GJA1, FOXL2, NR2F2, FBN1, COL1A1, NR5A1, CCND2, CCNE1 and ALDH1A1. Expression of CCND2, CCNE1, CCNE2, ESR2 and TGFBR1 was higher in the fetal fibroblasts than in adult fibroblasts; FBN1 was lower. Expression of OCLN, MUC1, LAMB2, NR5A1, ESR1, ESR2, and TGFBR3 was lower in GREL cells than ovarian surface epithelial cells. Expression of KRT19, DSG2, PKP2, OCLN, MUC1, FBN1, COL1A1, COL3A1, STAR and TGFBR2 was higher and GJA1, CTNNB1, LAMB2, NR5A1, CYP11A1, HSD3B1, CYP19A1, HSD17B1, FOXL2, ESR1, ESR2, TGFBR3 and CCND2 was lower in GREL cells compared to granulosa cells. TGFβ1 altered the expression of COL1A1, COL3A1 and FBN1 in fetal fibroblasts and epidermal growth factor altered the expression of FBN1 and COL1A1. In summary, the two major somatic cell types of the developing ovary have distinct gene expression profiles. They, especially GREL cells, also differ from the cells they ultimately differentiate in to. The regulation of cell fate determination, particularly of the bi-potential GREL cells, remains to be elucidated.

Geese are susceptible to oxidative stress during breeding, leading to senescence of granulosa cells (GCs) and reduced egg production. Adiponectin (ADPN) is a cytokine secreted by adipose tissue that functions to regulate metabolism and antioxidants. However, its role in the regulation of goose GCs is unclear. To investigate this, senescence in primary goose GCs was induced by D-gal and assessed via RT‒qPCR, senescence-associated β-galactosidase (SA-β-gal) staining, immunofluorescence, flow cytometry, and transcriptomics. The effect of ADPN on GC senescence was investigated by overexpressing and knocking down ADPN expression. The results showed that ADPN could alleviate oxidative stress and cell cycle arrest in GCs, reduce the expression of the senescence-associated secretory phenotype (SASP)-related genes IL-6 and IL-8, regulate the metabolic capacity of GCs, reduce the accumulation of SA-β-gal, maintain telomere length, and alleviate the senescence of GCs induced by D-gal. The RNA-seq results provided further evidence for the regulatory effect of ADPN on GC senescence. ADPN was shown to attenuate oxidative stress-induced GC senescence through the AGE (Advanced glycation end products)-RAGE (Receptor of advanced glycation end products) and NOD-like receptor pathways. These findings may contribute to the development of improved theoretical references for improving egg-laying performance and prolonging the service life of geese.

The transient receptor potential canonical 6 (TRPC6) channel, a nonselective cation channel that allows the passage of Ca2+, plays an important role in renal diseases. TRPC6 is activated by Ca2+ influx, oxidative stress, and mechanical stress. Studies have shown that in addition to glomerular diseases, TRPC6 can contribute to renal tubular disorders, such as acute kidney injury, renal interstitial fibrosis, and renal cell carcinoma (RCC). However, the tubule-specific physiological functions of TRPC6 have not yet been elucidated. Its pathophysiological role in ischemia/reperfusion (I/R) injury is debatable. Thus, TRPC6 may have dual roles in I/R injury. TRPC6 induces renal fibrosis and immune cell infiltration in a unilateral ureteral obstruction (UUO) mouse model. Additionally, TRPC6 overexpression may modify G2 phase transition, thus altering the DNA damage checkpoint, which can cause genomic instability and RCC tumorigenesis and can control the proliferation of RCC cells. This review highlights the importance of TRPC6 in various conditions of the renal tubular system. To better understand certain renal disorders and ultimately identify new therapeutic targets to improve patient care, the pathophysiology of TRPC6 must be clarified.

The study of upper ocean mixing processes, including their dynamics and thermodynamics, has been a primary focus for oceanographers and meteorologists. Wave breaking in deep water is believed to play a significant role in these processes, affecting air–sea interactions and contributing to the energy dissipation of surface waves. This, in turn, enhances the transfer of gas, heat, and mass at the ocean surface. In this paper, we use the FVCOM-SWAVE coupled wave and current model, which is based on the MY-2.5 turbulent closure model, to examine the response of upper ocean turbulent kinetic energy (TKE) and temperature to various wave breaking parametric schemes. We propose a new parametric scheme for wave breaking energy at the sea surface, which is based on the correlation between breaking wave parameter RB and whitecap coverage. The impact of this new wave breaking parametric scheme on the upper ocean under typhoon conditions is analyzed by comparing it with the original parametric scheme that is primarily influenced by wave age. The wave field simulated by SWAVE was verified using Jason-3 satellite altimeter data, confirming the effectiveness of the simulation. The simulation results for upper ocean temperature were also validated using OISST data and Argo float observational data. Our findings indicate that, under the influence of Typhoon Nanmadol, both parametric schemes can transfer the energy of sea surface wave breaking into the seawater. The new wave breaking parameter RB scheme effectively enhances turbulent mixing at the ocean surface, leading to a decrease in sea surface temperature (SST) and an increase in mixed layer depth (MLD). This further improves upon the issue of uneven mixing of seawater at the air–sea interface in the MY-2.5 turbulent closure model. However, it is important to note that wave breaking under typhoon conditions is only one aspect of wave impact on ocean disturbances. Therefore, further research is needed to fully understand the impact of waves on upper ocean mixing, including the consideration of other wave mechanisms.

Wave-induced radiation stress (RS), as a primary driver of ocean currents influenced by waves, plays an important role in the response of upper ocean temperatures under typhoons. Previous studies have mainly focused on wave-generated currents and coastal currents in nearshore areas. This paper incorporates the geostrophic effect into the wave-induced radiation stress of wave-current interaction, and the effect of waves on the changes in upper ocean temperature (including sea surface temperature (SST) and mixed layer temperature) under typhoon Nanmadol (2022) is studied. The FVCOM-SWAVE model is used to conduct a preliminary numerical study in the western Pacific Ocean. The RS with the geostrophic effect increased the horizontal and vertical components, leading to an enhancement in turbulent mixing and a decrease in SST by up to 1.0 °C to 1.4 °C, which is closer to the SST obtained by OISST remote sensing fusion observation data. In the strong divergence domain, the direction of the vortex flow exhibits a more pronounced turn to the right, accompanied by an increase in water velocity. The vertical temperature profile of the ocean shows that the water below is perturbed by the RS component of the geostrophic effect, and the depth of the mixed layer increases by about 2 m, which is closer to the depth of the mixed layer observed by the Argo floats, indirectly enhancing the vertical mass transport of the ocean. In general, this shows that RS, which takes into account geostrophic effects, enhances the effect of waves on the water below, indirectly leading to lower temperatures in the upper ocean, and the simulated results align more closely with the observed data, offering valuable insights for enhancing marine numerical forecasting accuracy.

Neuromedin B（NMB） is a member of mammalian bombesin-like peptide family and almost all its potent biological actions take place exclusively through its receptor NMBR,which has been identified as a G-protein couple receptor with seven trans-membrane regions.NMB and NMBR represent an interesting signaling axis over which NMB/NMBR perform multiple biological activities,in particularly,they have been highlighted in the regulation of the immunology system. This review aims to provide a brief overview of the recent advancements in our understanding regarding the potential immunological functions of NMB and NMBR in cell proliferation,tumorigenesis,angiogenesis,neurogenic inflammation,anti-influenza A virus（IAV） infections,and briefly discusses the potential importance of these observations. All these implicated that targeting NMBR or developing analogues of NMB may represent a useful strategy for development of new anti-IAV agents. [ABSTRACT FROM AUTHOR]

Abstract Background New-onset atrial fibrillation (NOAF) is a common complication in patients with acute myocardial infarction (AMI) during hospitalization. Galectin-3 (Gal-3) is a novel inflammation marker that is significantly associated with AF. The association between post-AMI NOAF and Gal-3 during hospitalization is yet unclear. Objective The present study aimed to investigate the predictive value of plasma Gal-3 for post-AMI NOAF. Methods A total of 217 consecutive patients admitted with AMI were included in this retrospective study. Peripheral venous blood samples were obtained within 24 h after admission and plasma Gal-3 concentrations were measured. Results Post-AMI NOAF occurred in 18 patients in this study. Patients with NOAF were older (p

A good safety and immunogenicity profile was reported in Phase I and II clinical trials of inactivated SARS-CoV-2 vaccines. Here, we report two cases associated with vaccine-associated adverse events, including one patient with fever and another with anaphylactic shock resulting from inactivated SARS-CoV-2 vaccination. Cell sub-types and the importance of genetic characteristics were assessed using single-cell mRNA sequencing and machine learning. Overall, the patient with fever showed a significant increase in the numbers of cytotoxic CD8 T cells and MKI67high CD8 T cells. A potential concurrent infection with the Epstein–Barr virus enhanced interferon type I responses to vaccination against the virus. STAT1, E2F1, YBX1, and E2F7 played a key role in the transcription regulation of MKI67high CD8 T cells. In contrast, the patient with allergic shock displayed predominant increases in the numbers of S100A9high monocytes, activated CD4 T cells, and PPBPhigh megakaryocytes. The decision tree showed that LYZ and S100A8 in S100A9high monocytes contributed to the degranulation of neutrophils and activation of neutrophils involved in allergic shock. PPBP and PF4 were major contributors to platelet degranulation. These findings highlight the diversity of adverse reactions following inactivated SARS-CoV-2 vaccination and show the emerging role of cellular subtypes and central genes in vaccine-associated adverse reactions.

Abstract Endothelial dysfunction is common in patients with chronic kidney disease (CKD), but the mechanism is unknown. In this study, we found that the circulating ANRIL level was increased and correlated with vascular endothelial dysfunction in patients with CKD, also negatively correlated with plasma brain-derived neurotrophic factor (BDNF) concentration. We constructed the ANRIL knockout mice model, and found that ANRIL deficiency reversed the abnormal expression of BDNF, along with endothelial nitric oxide synthase (eNOS), vascular adhesion molecule 1 (VCAM-1) and Von Willebrand factor (vWF). Meanwhile, mitochondrial dynamics-related proteins, Dynamin-related protein 1 (Drp1) and mitofusins (Mfn2) level were also recovered. In addition, in vitro, serum derived from CKD patients and uremia toxins induced abnormal expression of ANRIL. By making use of the gain- and loss-of-function approaches, we observed that ANRIL mediated endothelial dysfunction through BDNF downregulation. To explore the specific mechanism, RNA pull-down and RNA-binding protein immunoprecipitation (RIP) were used to explore the binding of ANRIL to histone methyltransferase Enhancer of zeste homolog 2 (EZH2). Further experiments found increased EZH2 and histone H3 lysine 27 trimethylation (H3K27me3) levels at the BDNF promoter region. Collectively, we demonstrated that ANRIL mediate BDNF transcriptional suppression through recruitment of EZH2 to the BDNF promoter region, then regulated the proteins expression related to endothelial function and mitochondrial dynamics. This study provides new insights for the study of endothelial dysfunction in CKD.

Introduction: This study systematically reviewed scientific evidence concerning the influence of green space on obesity in China. Methods: Keyword and reference search was conducted in PubMed, Web of Science, Scopus, EBSCO, and CNKI. Predetermined selection criteria included study designs: experimental and observational studies; subjects: people of all ages; exposures: green space (i.e., any open land partly or entirely covered with grass, trees, shrubs, or other vegetation); outcomes: body weight status (e.g., body mass index [BMI], overweight, or obesity); and country: China. Results: Ten studies met the selection criteria and were included in the review. All studies adopted a cross-sectional design. Overall greenness measures were found to be inversely associated with BMI, overweight, and obesity in most included studies. Street greenness, which measures the perceived greenness at the eye level on streets, was found to be inversely associated with BMI and obesity. By contrast, mixed results were observed for the relationship between green space accessibility and weight outcomes. Air quality was found to mediate the relationship between greenness and obesity. The influence of green space on obesity tended to vary by residents’ gender, age, and socioeconomic status. Boys, women, older residents, and those with lower education or household income were more likely to benefit from greenness exposure. Conclusion: The literature on green space exposure in relation to obesity in China remains limited. Longitudinal and quasi-experimental studies are warranted to assess the causal link between green space and obesity. Future measures should better capture the self-perception, quality, and attractiveness of green space. The underlying pathways through which green space affects residents’ weight outcomes should be further elucidated.

The wave period is a wave parameter that is significantly influenced by factors such as wind speed and bottom topography. Previous research on wave period parameterization has primarily focused on wind-dominated sea areas and may not be applicable to certain regions, such as the equatorial calm or coastal areas dominated by swell waves. To address this limitation, this paper utilizes the third-generation wave numerical model SWAN to perform wave numerical simulations for a portion of the Northwest Pacific Ocean. The simulation incorporates observational data from nearshore stations, buoys, and satellite altimeters for error analysis. To develop a new wave parameterization scheme (WS-23), we employ extensive NDBC buoy data and incorporate the exponential rate and wave age characteristics that were previously established by predecessors. Our scheme introduces a judgement mechanism to distinguish between wind waves, swell waves, and mixed waves. The resulting ocean wave factor enhances the mean wave period values calculated using the model and other parameterization schemes. The experimental results demonstrate that our new parameterization scheme effectively improves the abnormal peak of the fitting data. Comparing the output values of the mean wave period element output of the SWAN model with our new parameterization scheme, we observe a reduction in the mean values of Ea, Ec, and RMSE by 0.231, 1.94%, and 0.162, respectively, while increasing the average r by 0.05.

For the first time, a novel dithiomaleimides (DTM) based tetra-antennary GalNAc conjugate was developed, which enable both efficient siRNA delivery and good traceability, without incorporating extra fluorophores. This conjugate can be readily constructed by three click-type reactions, that is, amidations, thiol-dibromomaleimide addition and copper catalyzed azide–alkyne cycloaddition (CuAAC). And it also has comparable siRNA delivery efficiency, with a GalNAc L96 standard to mTTR target. Additionally, due to the internal DTMs, a highly fluorescent emission was observed, which benefited delivery tracking and reduced the cost and side effects of the extra addition of hydrophobic dye molecules. In all, the simple incorporation of DTMs to the GalNAc conjugate structure has potential in gene therapy and tracking applications.

Parkinson's disease (PD) is a familiar neurodegenerative disease, accompanied by motor retardation, static tremor, memory decline and dementia. Heredity, environment, age and oxidative stress have been suggested as key factors in the instigation of PD. The Keap1-Nrf2-ARE signaling is one of the most significant anti- oxidative stress (OS) pathways. The Keap1 is a negative regulator of the Nrf2. The Keap1-Nrf2-ARE pathway can induce cell oxidation resistance and reduce nerve injury to treat neurodegenerative diseases. Ellagic acid (EA) can inhibit the Keap1 to accumulate the Nrf2 in the nucleus, and act on the ARE to produce target proteins, which in turn may alleviate the impact of OS on neuronal cells of PD. This review analyzes the structure and physiological role of EA, along with the structure, composition and functions of the Keap1-Nrf2-ARE signaling pathway. We further expound on the mechanism of ellagic acid in its activation of the Keap1-Nrf2-ARE signaling pathway, as well as the relationship between EA in impairing the TLR4/Myd88/NF-κB and Nrf2 pathways. Ellagic acid has the potentiality of improving PD by activating the Keap1-Nrf2-ARE signaling pathway and scavenging free radicals.

Abstract Background Galectin-3 (Gal-3) is currently recognized as a promising biomarker for myocardial fibrosis. This study aimed to explore the potential association between plasma Gal-3 concentrations and atrial fibrillation (AF) progression in paroxysmal AF (PAF) patients Methods A total of 213 PAF patients were included for analysis in this study. All peripheral blood samples were prospectively collected and stored at -80℃ for subsequent Gal-3 quantification. The AF progression was defined as transformation from PAF to persistent AF (PsAF). Results A total of 51 PAF patients progressed to PsAF during a mean follow-up period of 674.44 ± 19.48 days. Patients with AF progression had significantly higher baseline plasma Gal-3 concentrations than those stayed in PAF status (13.52 ± 0.94 vs. 7.93 ± 0.37, p

Radiation stress is defined as the excess momentum caused by ocean waves, which exerts an indispensable impact on the upper-layer ocean conditions as waves pass by. Previous research concentrated on sea surface cooling caused by typhoons. In this paper, we investigated the effect of wave-induced radiation stress on upper-layer ocean temperature (including sea surface temperature (SST) and mixed-layer temperature) under typhoon conditions, as well as the effect of radiation stress on the surface current field. The FVCOM-SWAVE model, which is based on the SWAN model, is used to simulate the response of upper-layer ocean temperature to radiation stress. The simulated results, when validated with Jason-3 satellite and ARGO data, could reproduce the observed phenomenon well in general. Compared to simulations without radiation stress, the bias in the SST results is reduced by about 1 °C if the radiation stress term is taken into account. The mixed-layer depth temperature is expected to be simulated more accurately, with a root mean square error (RMSE) of less than 1.63 °C and a correlation coefficient (COR) of about 0.94. Results show that wave-induced radiation stress enhances the surface current and causes certain deviations to the right so that the upper water diverges and upwelling increases, resulting in a decrease in SST. When the influence of double typhoons is considered, the airflow of LEKIMA(L) rotates from the northwest toward KROSA (R), limiting the development of significant wave height (SWH) and reducing the cooling range. As a result, the present study is of tremendous importance in precisely forecasting the ocean state of the western North Pacific (WNP).

Abstract Background Acute kidney injury (AKI), with a high morbidity and mortality, is recognized as a risk factor for chronic kidney disease (CKD). AKI-CKD transition has been regarded as one of the most pressing unmet needs in renal diseases. Recently, studies have showed that salt inducible kinase 1 (SIK1) plays a role in epithelial-mesenchymal transition (EMT) and inflammation, which are the hallmarks of AKI-CKD transition. However, whether SIK1 is involved in AKI-CKD transition and by what mechanism it regulates AKI-CKD transition remains unknown. Methods We firstly detected the expression of SIK1 in kidney tissues of AKI patients and AKI mice by immunohistochemistry staining, and then we established Aristolochic acid (AA)-induced AKI-CKD transition model in C57BL/6 mice and HK2 cells. Subsequently, we performed immunohistochemistry staining, ELISA, real-time PCR, Western blot, immunofluorescence staining and Transwell assay to explore the role and underlying mechanism of SIK1 on AKI-CKD transition. Results The expression of SIK1 was down-regulated in AKI patients, AKI mice, AA-induced AKI-CKD transition mice, and HK2 cells. Functional analysis revealed that overexpression of SIK1 alleviated AA-induced AKI-CKD transition and HK2 cells injury in vivo and in vitro. Mechanistically, we demonstrated that SIK1 mediated AA-induced AKI-CKD transition by regulating WNT/β-catenin signaling, the canonical pathway involved in EMT, inflammation and renal fibrosis. In addition, we discovered that inhibition of WNT/β-catenin pathway and its downstream transcription factor Twist1 ameliorated HK2 cells injury, delaying the progression of AKI-CKD transition. Conclusions Our study demonstrated, for the first time, a protective role of SIK1 in AKI-CKD transition by regulating WNT/β-catenin signaling pathway and its downstream transcription factor Twist1, which will provide novel insights into the prevention and treatment AKI-CKD transition in the future.

Abstract Introduction The progression of paroxysmal AF (PAF) to persistent AF (PsAF) worsens the prognosis of AF, but its underlying mechanisms remain elusive. Recently, circular RNAs (circRNAs) were reported to be associated with cardiac fibrosis. In case of the vital role of cardiac fibrosis in AF persistency, we hypothesis that circRNAs may be potential regulators in the process of AF progression. Materials and methods 6 persistent and 6 paroxysmal AF patients were enrolled as derivation cohort. Plasma circRNAs expressions were determined by microarray and validated by RT-PCR. Fibrosis level, manifested by serum TGF-β, was determined by ELISA. Pathways and related non-coding RNAs involving in the progression of AF regulated were predicted by in silico analysis. Results PsAF patients showed a distinct circRNAs expression profile with 92 circRNAs significantly dysregulated (fold change ≥ 2, p

Chronic kidney disease (CKD) has been recognized as an increasingly serious public health problem globally over the decades. Accumulating evidence has shown that the incidence rate of cancer was relatively higher in CKD patients than that in general population, which, mechanistically, may be related to chronic inflammation, accumulation of carcinogenic compounds, oxidative stress, impairment of DNA repair, excessive parathyroid hormone and changes in intestinal microbiota, etc. And in patients with cancer, regardless of tumor types or anticancer treatment, it has been indicated that the morbidity and incidence rate of concomitant CKD was also increased, suggesting a complex inter-relationship between CKD and cancer and arousing increasing attention from both nephrologists and oncologists. This narrative review focused on the correlation between CKD and cancer, and underlying molecular mechanisms, which might provide an overview of novel interdisciplinary research interests and the potential challenges related to the screening and treatment of CKD and cancer. A better understanding of this field might be of help for both nephrologists and oncologists in the clinical practice.

Diabetic kidney disease (DKD) is one of the major microvascular complications of diabetes mellitus, with relatively high morbidity and mortality globally but still in short therapeutic options. Over the decades, a large body of data has demonstrated that oxidative stress, inflammatory responses, and hemodynamic disorders might exert critical influence in the initiation and development of DKD, whereas the delicate pathogenesis of DKD remains profoundly elusive. Recently, long non-coding RNAs (lncRNAs), extensively studied in the field of cancer, are attracting increasing attentions on the development of diabetes mellitus and its complications including DKD, diabetic retinopathy, and diabetic cardiomyopathy. In this review, we chiefly focused on abnormal expression and function of lncRNAs in major resident cells (mesangial cell, endothelial cell, podocyte, and tubular epithelial cell) in the kidney, summarized the critical roles of lncRNAs in the pathogenesis of DKD, and elaborated their potential therapeutic significance, in order to advance our knowledge in this field, which might help in future research and clinical treatment for the disease.

Abstract Background There is a paucity of evidence on the combination of the SYNTAX score II (SSII) and erythrocyte sedimentation rate (ESR) in assessing the long-term prognosis of patients with ST-elevated myocardial infarction (STEMI) and multivessel disease. The objective of this study was to investigate whether the ESR could enhance the predictive value of SSII on the long-term prognosis of STEMI patients. Methods A retrospective cohort study involving 483 STEMI and multivessel disease subjects receiving primary percutaneous coronary intervention was conducted. Major adverse cardiovascular events (MACE) included cardiovascular death, acute heart failure, recurrent myocardial infarction, revascularization, and nonfatal stroke. The predicted values of different models were estimated by a likelihood ratio test, Akaike’s information criteria (AIC), receiver operating characteristic (ROC) curves, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). Results During the follow-up period of up to 52 months, both the SSII and ESR were independently associated with MACE (hazard ratio [HR] = 1.032, p

Diabetic kidney disease (DKD) is one of the most common complications of diabetes mellitus (DM), without suitable therapies, causing end-stage renal diseases (ESRDs) ultimately. Moreover, there is increasing evidence demonstrating that long noncoding RNAs (lncRNAs) play crucial roles in the development of DKD. Our RNA sequencing data revealed a large group of differentially expressed lncRNAs in renal tissues of DKD, of which lncRNA ENSG00000254693 (lncRNA 254693 for short) changed drastically. In this study, we found that the expression of lncRNA 254693 was increased in both DKD patients and high-glucose-induced human podocytes. 5′/3′RACE and Northern blot assays were used to find the full length of lncRNA ENSG00000254693 which is 558 nucleotides and nonisoform that existed in human podocyte. Downregulation of lncRNA 254693 remarkably reversed the elevation of inflammation, apoptosis, and podocyte injury caused by high glucose. Then, we did bioinformatics analysis via RBPDB and found that lncRNA 254693 can combine with HuR, a RNA binding protein. Meanwhile, immunofluorescence and in situ hybridization double staining was used to prove the existence of colocalization between them. Intriguingly, lncRNA 254693 knockdown decreased HuR levels, while HuR knockdown also decreased the level of lncRNA 254693 and its stability. After this, RNA immunoprecipitation assay results confirmed the binding association between them again. In addition, we found that HuR was increased in high glucose-induced podocytes, and the silence of HuR could alleviate podocyte injury, inflammation, and apoptosis. These results together suggested a novel feedback regulation between lncRNA 254693 and HuR which could involve in podocyte injury and may serve as a predicted target for DKD therapies.

BackgroundAging is significantly associated with the incidence and progression of atrial fibrillation (AF) incidence. This study aimed to evaluate the potential predictive value of leukocyte telomere length (LTL) for progression from paroxysmal AF (PAF) to persistent AF (PsAF) after catheter ablation.Methods and ResultsA total of 269 patients with AF (154 patients with PAF and 115 patients with PsAF, respectively) were prospectively enrolled, and all patients with PAF at baseline were regularly followed up to determine whether and when they should progress to PsAF after catheter ablation therapy. Baseline relative LTL was measured by quantitative real-time PCR (rt-PCT). There was a significant negative association between LTL and age (r = −0.23, p < 0.001). Patients with PsAF had significantly shorter LTL than those with PAF. After a mean follow-up of 854.9 ± 18.7 d, progression events occurred in 35 out of the 154 patients with PAF. Those progressed patients with PAF were older (70.9 ± 8.0 vs. 62.3 ± 10.3, p < 0.001) and had shorter LTL (1.2 ± 0.3 vs. 1.5 ± 0.3, p < 0.001) than those who did not. The receiver operating characteristic (ROC) curve analysis showed a significant value of LTL in distinguishing patients with PAF from patients with PsAF, with an area under the ROC curve (AUC) of 0.63 (95% CI 0.56–0.70, p < 0.001), and the optimal cut-off value of LTL was 1.175, with a sensitivity and specificity of 56.03 and 82.04%, respectively. All patients with PAF were divided into two subgroups according to the optimal cut-off point of LTL calculated by the ROC curve analysis: high LTL group (≥1.175) and low LTL group (

ABSTRACTHepatitis E virus (HEV) can lead to high mortality during pregnancy. This study was to investigate the adverse pregnancy outcomes caused by different HEV genotypes and their prevention by HEV 239 vaccine in rabbits. Forty-two female rabbits were randomly and equally divided into 7 groups (A-G). HEV 239 vaccine and a placebo were administered to groups E (10 μg×2), F (5 μg×2) and G (1 mL of PBS×2) before copulation. After pregnancy, 1 mL of 1.5×106 copies/mL rabbit HEV3 was inoculated to groups A, E, F and G, swine HEV4/human HEV3 to groups B/C, and group D was a negative control. Anti-HEV antibody, HEV RNA, and alanine aminotransferase (ALT)/aspartate aminotransferase (AST) levels were monitored. Pregnant rabbits infected by HEV manifested HEV infection symptoms including fecal virus shedding, ALT/AST elevation, and histopathological changes, and adverse pregnancy outcomes. Immunized pregnant rabbits in groups E and F showed no HEV infection symptoms and adverse outcomes. The newborn rabbits delivered by pregnant rabbits with/without immunization showed without/with HEV infection symptoms. This study demonstrated that multiple genotypes of HEV infection can cause adverse outcomes and HEV 239 vaccine can prevent HEV-related adverse outcomes in pregnant rabbits.

Bone morphogenetic protein 15 (BMP15) is secreted by the mammalian oocytes and is indispensable for ovarian follicular development, ovulation, and fertility. To determine the regulation mechanism of BMP15 gene, the regulatory sequence of porcine BMP15 was investigated in this study. The cloned BMP15 promoter retains the cell-type specificity, and is activated in cells derived from ovarian tissue. The luciferase assays in combination with a series of deletion of BMP15 promoter sequence show that the -427 to -376 bp region of BMP15 promoter is the primary regulatory element, in which there are a number of transcription factor binding sites, including LIM homeobox 8 (LHX8), newborn ovary homeobox gene (NOBOX), and paired-like homeodomain transcription factor 1 (PITX1). Determination of tissue-specific expression reveals that LHX8, but not PITX1 and NOBOX, is exclusively expressed in pig ovary tissue and is translocated into the cell nuclei. Overexpression of LHX8 in Chinese hamster ovary (CHO) cells could significantly promote BMP15 promoter activation. This study confirms a key regulatory element that is located in the proximal region of BMP15 promoter and is regulated by the LHX8 factor. [ABSTRACT FROM AUTHOR]

ObjectivesTo investigate the association between inflammatory indices and clinical outcomes of hepatocellular carcinoma (HCC) patients treated with transarterial chemoembolization (TACE) by performing meta-analysis.MethodsA systematic literature search for relevant studies published up to August 2019 was performed by using PubMed, Web of Science, EMBASE, China National Knowledge Internet (CNKI) and Wanfang databases. Pooled hazard ratios (HR) or odds ratio (OR) and 95% confidence intervals (95% CI) were calculated.ResultsA total of 5280 patients from 22 studies were finally enrolled in the meta-analysis. The results demonstrated that elevated preoperative NLR, PLR, and CRP was associated with poor OS in HCC patients treated by TACE (HR = 1.81, P3 cm (OR = 2.42, P = 0.005).ConclusionsElevated preoperative NLR, PLR, and CRP are associated with poor prognosis in HCC patients treated with TACE. These inflammatory indices may be convenient, accessible, affordable and dependable biomarkers with prognostic potential for HCC patients treated by TACE.