bluuebunny/crossref_metadata_2025 huggingface dataset:
The rs7404339 AA Genotype in CDH5 Contributes to Increased Risks of Kawasaki Disease and Coronary Artery Lesions in a Southern Chinese Child Population
Authors: Wang Yishuai , Lin Kun , Zhang Linyuan , Lin Yueling , Yu Hongyan , Xu Yufen , Fu Lanyan , Pi Lei , Li Jinqing , Mai Hanran , Wei Bing , Jiang Zhiyong , Che Di , Gu Xiaoqiong
Published: April 2022

Background

Kawasaki disease (KD) is an acute, self-limited febrile illness of unknown cause. And it predominantly affects children <5 years and the main complication is coronary artery lesion (CAL). Studies demonstrated that vascular endothelial cells (VECs) played a very important role in the CAL of KD. VE-cad encoded by CDH5 may exert a relevant role in endothelial cell biology through controlling the cohesion of the intercellular junctions. The pathogenesis of KD remains unclear and genetic factors may increase susceptibility of KD. However, the relationship between CDH5 polymorphisms and KD susceptibility has not been reported before. The present study is aimed at investigating whether the rs7404339 polymorphism in CDH5 is associated with KD susceptibility and CAL in a southern Chinese child population.

Methods and Results

We recruited 1,335 patients with KD and 1,669 healthy children. Each participant had supplied 2 mL of fresh blood in the clinical biologic bank at our hospital for other studies. Multiplex PCR is used to assess the genotypes of rs7404339 polymorphism in CDH5. According to the results, we found significant correlated relationship between rs7404339 polymorphism in CDH5 and KD susceptibility [AA vs. GG: adjusted odds ratio (OR) = 1.43, 95% confidence interval (CI) = 1.00–2.05; p = 0.0493; recessive model: adjusted OR = 1.44, 95% CI = 1.01–2.06, P = 0.0431]. In further stratified analysis, we found that children younger than 60 months (adjusted OR = 1.46, 95% CI = 1.01–2.10; p = 0.0424) and male (adjusted OR = 1.70, 95% CI = 1.09–2.65; p = 0.0203) with the rs7404339 AA genotype in CDH5 had a higher risk of KD than carriers of the GA/GG genotype. Furthermore, stratification analysis revealed that patients with the rs7404339 AA genotype exhibited the significantly higher onset risk for CAL than carriers of the GA/GG genotype (adjusted age and gender odds ratio = 1.56, 95% CI = 1.01–2.41; P = 0.0433).

Conclusion

Our results showed that rs7404339 AA genotype in CDH5 is significant associated with KD susceptibility. And children younger than 60 months and male with the rs7404339 AA genotype had a higher risk of KD than carriers with the GA/GG genotype. Furthermore, patients with the rs7404339 AA genotype exhibited a significantly higher risk of CAL complication than carriers of the GA/GG genotype.
Ca2+/Calmodulin-Dependent Protein Kinase II Regulation by RIPK3 Alleviates Necroptosis in Transverse Arch Constriction-Induced Heart Failure
Authors: Cao Ji , Zhang Jingjing , Qian Jianan , Wang Xue , Zhang Wei , Chen Xiangfan
Published: April 2022

Some studies have reported that the activation of Ca2+/calmodulin dependent protein kinase (CaMKII) plays a vital role in the pathogenesis of cardiovascular disease. Moreover, receptor interacting protein kinase 3 (RIPK3)-mediated necroptosis is also involved in the pathological process of various heart diseases. In the present study, we aimed to investigate the effect of RIPK3-regulated CaMKII on necroptosis in heart failure (HF) and its underlying mechanism. Wild type (WT) and RIPK3-depleted (RIPK3–/–) mice were treated with transverse arch constriction (TAC). After 6 weeks, echocardiography, myocardial injury, CaMKII activity, necroptosis, RIPK3 expression, mixed lineage kinase domain-like protein (MLKL) phosphorylation, and mitochondrial ultrastructure were measured. The results showed that TAC aggravated cardiac dysfunction, CaMKII activation, and necroptosis in WT mice. However, depletion of RIPK3 alleviated cardiac insufficiency, CaMKII activation, and necroptosis in TAC-treated mice. To verify the experimental results, WT mice were transfected with AAV-vector and AAV-RIPK3 shRNA, followed by TAC operation. The findings were consistent with the expected results. Collectively, our current data indicated that the activation of CaMKII, MLKL and necroptosis in HF mice were increased in a RIPK3-dependent manner, providing valuable insights into the pathogenesis and treatment strategy of HF.
The Relationship Between Body Mass Index and In-hospital Survival in Patients Admitted With Acute Heart Failure
Authors: Elbaz-Greener Gabby , Rozen Guy , Carasso Shemy , Yarkoni Merav , Wijeysundera Harindra C. , Alcalai Ronny , Gotsman Israel , Rahamim Eldad , Planer David , Amir Offer
Published: April 2022

Background

The association between Body Mass Index (BMI) and clinical outcomes following acute heart failure (AHF) hospitalization is debated in the literature. Our objective was to study the real-world relationship between BMI and in-hospital mortality in patients who were admitted with AHF.

Methods

In this retrospective, multi-center study, we utilized the National Inpatient Sample (NIS) database to identify a sampled cohort of patients who were hospitalized with AHF between October 2015 and December 2016. Outcomes of interest included in-hospital mortality and length of stay (LOS). Patients were divided into 6 BMI (kg/m2) subgroups according to the World Health Organization (WHO) classification: (1) underweight ≤ 19, (2) normal weight 20–25, (3) overweight 26–30, (4) obese I 31–35, (5) obese II 36–39, and (6) extremely obese ≥40. A multivariable logistic regression model was used to identify predictors of in-hospital mortality and to identify predictors of LOS.

Results

A weighted total of 219,950 hospitalizations for AHF across the US were analyzed. The mean age was 66.3 ± 31.5 years and most patients (51.8%) were male. The crude data showed a non-linear complex relationship between BMI and AHF population outcomes. Patients with elevated BMI exhibited significantly lower in-hospital mortality compared to the underweight and normal weight study participants (5.5, 5,5, 2,8, 1.6, 1.4, 1.6% in groups by BMI ≤ 19, 20–25, 26–30, 31–35, 36–39, and, ≥40 respectively, p < 0.001) and shorter LOS. In the multivariable regression model, BMI subgroups of ≤ 25kg/m2 were found to be independent predictors of in-hospital mortality. Age and several comorbidities, and also the Deyo Comorbidity Index, were found to be independent predictors of increased mortality in the study population.

Conclusion

A reverse J-shaped relationship between BMI and mortality was documented in patients hospitalized for AHF in the recent years confirming the “obesity paradox” in the real-world setting.
Extracellular Nucleophosmin Is Increased in Psoriasis and Correlates With the Determinants of Cardiovascular Diseases
Authors: D'Agostino Marco , Beji Sara , Sileno Sara , Lulli Daniela , Mercurio Laura , Madonna Stefania , Cirielli Corrado , Pallotta Sabatino , Albanesi Cristina , Capogrossi Maurizio C. , Avitabile Daniele , Melillo Guido , Magenta Alessandra
Published: April 2022

We previously showed that genotoxic stress induced an active extracellular release of nucleophosmin (NPM) in human cardiac mesenchymal progenitor cells, and that serum deprivation provokes NPM secretion from human endothelial cells, eliciting inflammation via nuclear factor kappa B (NF-kB) transcriptional activation. In this study, we wanted to determine whether NPM was similarly modulated in the skin and plasma of psoriatic patients (Pso). We found that NPM was induced in 6 skin biopsies compared to 6 normal skin biopsies and was markedly increased in lesional (LS) vs. non-lesional skin (NLS) biopsies. Moreover, NPM was also increased at the transcriptional levels in LS vs. NLS. Both the innate stimuli, such as lipopolysaccharides and Poly inositol–cytosine and adaptive stimuli, that is, cytokine mix, were able to induce the extracellular release of NPM in immortalized keratinocytes and human skin fibroblasts in the absence of cytotoxicity. Interestingly, NPM interacts with Toll-like receptor (TLR)4 in these cells and activates an NF-kB-dependent inflammatory pathway upregulating interleukin IL-6 and COX-2 gene expression. Finally, circulating NPM was increased in the plasma of 29 Pso compared to 29 healthy controls, and positively correlates with psoriasis area severity index (PASI) and with determinants of cardiovascular diseases (CVDs), such as pulse wave velocity, systolic pressure, and left ventricular mass. Furthermore, NPM positively correlates with miR-200c circulating levels, which we previously showed to increase in Pso and correlate with CVD progression. Our data show that circulating miR-200c is physically associated with extracellular NPM, which most probably is responsible for its extracellular release and protection upon cytokine mix via a TLR4-mechanism. In conclusion, NPM is increased in psoriasis both in the skin and plasma and might be considered a novel biologic target to counteract chronic inflammation associated with CVD risk.
End-to-End Deep Learning of Non-rigid Groupwise Registration and Reconstruction of Dynamic MRI
Authors: Yang Junwei , Küstner Thomas , Hu Peng , Liò Pietro , Qi Haikun
Published: April 2022

Temporal correlation has been exploited for accelerated dynamic MRI reconstruction. Some methods have modeled inter-frame motion into the reconstruction process to produce temporally aligned image series and higher reconstruction quality. However, traditional motion-compensated approaches requiring iterative optimization of registration and reconstruction are time-consuming, while most deep learning-based methods neglect motion in the reconstruction process. We propose an unrolled deep learning framework with each iteration consisting of a groupwise diffeomorphic registration network (GRN) and a motion-augmented reconstruction network. Specifically, the whole dynamic sequence is registered at once to an implicit template which is used to generate a new set of dynamic images to efficiently exploit the full temporal information of the acquired data via the GRN. The generated dynamic sequence is then incorporated into the reconstruction network to augment the reconstruction performance. The registration and reconstruction networks are optimized in an end-to-end fashion for simultaneous motion estimation and reconstruction of dynamic images. The effectiveness of the proposed method is validated in highly accelerated cardiac cine MRI by comparing with other state-of-the-art approaches.
Long-Term Effect of Febuxostat on Endothelial Function in Patients With Asymptomatic Hyperuricemia: A Sub-Analysis of the PRIZE Study
Authors: Maruhashi Tatsuya , Higashi Yukihito , Yoshida Hisako , Tanaka Atsushi , Eguchi Kazuo , Tomiyama Hirofumi , Kario Kazuomi , Kato Toru , Oda Nozomu , Tahara Nobuhiro , Oguri Mitsutoshi , Watada Hirotaka , Node Koichi
Published: April 2022

Background

Xanthine oxidase is involved in the production of uric acid and the generation of superoxide anion. We evaluated the long-term effect of febuxostat, a non-purine selective xanthine oxidase inhibitor, on endothelial function in patients with asymptomatic hyperuricemia.

Methods

In the PRIZE study, patients with hyperuricemia were randomly assigned to either add-on febuxostat treatment (febuxostat group) or non-pharmacologic hyperuricemia treatment (control group). Among the 514 participants, endothelial function was assessed in 41 patients in the febuxostat group and 38 patients in the control group by flow-mediated vasodilation (FMD) of the brachial artery at the beginning of the study and after 12 and/or 24 months of treatment (63 men; median age, 68.0 years).

Results

The least squares mean concentration of serum uric acid was significantly lower in the febuxostat group than in the control group at 6 months (mean between-group difference [febuxostat group - control group], −2.09 mg/dL [95% confidence interval (CI), −2.520 to −1.659]; P < 0.001), 12 months (mean between-group difference, −2.28 mg/dL [95% CI, −2.709 to −1.842]; P < 0.001), and 24 months (mean between-group difference, −2.61 mg/dL [95% CI, −3.059 to −2.169]; P < 0.001). No significant differences were found between groups in the least squares mean estimated percentage change in FMD at 12 months (mean between-group difference, −0.56% [95% CI, −1.670 to 0.548]; P = 0.319) and at 24 months (mean between-group difference, −0.60% [95% CI, −1.886 to 0.685]; P = 0.357).

Conclusion

Febuxostat treatment did not alter endothelial function assessed by FMD during a 2-year study period in patients with asymptomatic hyperuricemia.
Deletion of the Pyrophosphate Generating Enzyme ENPP1 Rescues Craniofacial Abnormalities in the TNAP−/− Mouse Model of Hypophosphatasia and Reveals FGF23 as a Marker of Phenotype Severity
Authors: Nam Hwa Kyung , Emmanouil Emmanouil , Hatch Nan E.
Published: April 2022

Hypophosphatasia is a rare heritable metabolic disorder caused by deficient Tissue Non-specific Alkaline Phosphatase (TNAP) enzyme activity. A principal function of TNAP is to hydrolyze the tissue mineralization inhibitor pyrophosphate. ENPP1 (Ectonucleotide Pyrophosphatase/Phosphodiesterase 1) is a primary enzymatic generator of pyrophosphate and prior results showed that elimination of ENPP1 rescued bone hypomineralization of skull, vertebral and long bones to different extents in TNAP null mice. Current TNAP enzyme replacement therapy alleviates skeletal, motor and cognitive defects but does not eliminate craniosynostosis in pediatric hypophosphatasia patients. To further understand mechanisms underlying craniosynostosis development in hypophosphatasia, here we sought to determine if craniofacial abnormalities including craniosynostosis and skull shape defects would be alleviated in TNAP null mice by genetic ablation of ENPP1. Results show that homozygous deletion of ENPP1 significantly diminishes the incidence of craniosynostosis and that skull shape abnormalities are rescued by hemi- or homozygous deletion of ENPP1 in TNAP null mice. Skull and long bone hypomineralization were also alleviated in TNAP−/−/ENPP1−/− compared to TNAP−/−/ENPP1+/+ mice, though loss of ENPP1 in combination with TNAP had different effects than loss of only TNAP on long bone trabeculae. Investigation of a relatively large cohort of mice revealed that the skeletal phenotypes of TNAP null mice were markedly variable. Because FGF23 circulating levels are known to be increased in ENPP1 null mice and because FGF23 influences bone, we measured serum intact FGF23 levels in the TNAP null mice and found that a subset of TNAP−/−/ENPP1+/+ mice exhibited markedly high serum FGF23. Serum FGF23 levels also correlated to mouse body measurements, the incidence of craniosynostosis, skull shape abnormalities and skull bone density and volume fraction. Together, our results demonstrate that balanced expression of TNAP and ENPP1 enzymes are essential for microstructure and mineralization of both skull and long bones, and for preventing craniosynostosis. The results also show that FGF23 rises in the TNAP−/− model of murine lethal hypophosphatasia. Future studies are required to determine if the rise in FGF23 is a cause, consequence, or marker of disease phenotype severity.
Movable Fluid Distribution Characteristics and Microscopic Mechanism of Tight Reservoir in Yanchang Formation, Ordos Basin
Authors: Wu Ke , Chen Dezhao , Zhang Weigang , Yang Hua , Wu Hanning , Cheng Xin , Qu Yiqian , He Mengqing
Published: April 2022

Tight sandstone reservoirs have smaller pore throats, complex structures, strong heterogeneity in the pore throat system, and significant differences in fluid distribution. To reveal the occurrence characteristics of movable fluids in tight sandstone reservoirs, the typical tight sandstone core samples from the Chang 4+5 reservoir of the Upper Triassic Yanchang Formation of the Ordos Basin were selected and the micro pore throat classification standard was established by using casting thin slices, field emission scanning electron microscopy (FE-SEM), high-pressure mercury injection (HPMI), and nuclear magnetic resonance (NMR) technology. The test analysis results showed that the Chang 4+5 tight sandstone reservoir can be divided into Type I, II, and III reservoirs by the different pore throat structure. Type I reservoirs have well-developed pore throats, good connectivity, low threshold pressure (0.42 MPa on average), high movable fluid saturation (46.82% on average), and a minimum pore throat radius of movable fluid (0.056 μm on average). The pore throat structure and fluid production degree of the other two reservoir types gradually deteriorated. Note that the tight sandstone reservoirs of the Chang 4+5 reservoirs have smaller pore throats but high movable fluid content in smaller pore throats (17% on average). With the deterioration of the pore throat structure in reservoir, the degree of fluid utilization in larger pore throats decreases (74.33%–57.33%), whereas the degree of fluid utilization in smaller pore throats does not change significantly (25.67%–13.82%). Many factors affect movable fluid parameters. The movable fluid parameters of tight sandstone reservoirs in the Chang 4+5 reservoir have a good positive correlation with permeability (R2 = 0.85) and sorting coefficients (R2 = 0.88). The movable fluid parameters of smaller and larger pore throats have no obvious correlation with a single factor. Multiple factors affect the fluid occurrence characteristics of different scale pore throats.
Geochronology and Paleoenvironmental Changes of Late Pleistocene Sediments in the Ross Sea, Antarctica
Authors: Li Guogang , Bu Ruyuan , Yi Liang , Hu Bangqi , Li Yunhai , Ji Youjun , Li Yixin , Wang Liang
Published: April 2022

The palaeoceanographic studies are largely limited by poor carbonate preservation in high-latitude regions. To improve our knowledge in this key area, we studied a sediment core (ANT32-RA05C) in terms of paleomagnetic and 230Th dating and geochemical properties, collected from the continental slope of the Ross Sea, Antarctica. The two major results are as follows: 1) the sedimentation rate based on 230Th isotopes is 1.37 cm/kyr, agreeing well with the correlation of the relative paleomagnetic intensity of the core ANT32-RA05C to changes in Earth’s magnetic intensity and 2) the sediments contain ice-rafted debris (IRD) over 30%, with a considerable contribution of siliceous deposits. Integrating geochronological and geochemical properties of the studied core, a correlation of the regional paleoenvironmental process to the EPICA Dome C (EDC) Antarctic temperature is established, inferring that the IRD input and primary productivity are both enhanced in a warm climate. Moreover, a leading phase of biogenic processes to changes in the ice sheet in the Ross Ice Shelf is observed, highlighting a dominant role of the oceanic circulation in the ice-sheet retreat during the last deglaciation. Overall, the sedimentary record in the Ross Sea documents some key features of the paleoenvironmental processes in the Late Pleistocene, which could be correlated with large-scale changes in Antarctica and thus are worthy of further investigation in the future.
Spatial-Temporal Evolution of the Gas Hydrate Stability Zone and Accumulation Patterns of Double BSRs Formation in the Shenhu Area
Authors: Song Yingrui , Lei Yuhong , Zhang Likuan , Cheng Ming , Li Chao , Liu Naigui
Published: April 2022

The current study examines the methane gas hydrate stability zone (GHSZ) in the Shenhu area in the northern South China Sea (SCS) as an example to calculate the thickness of the GHSZ and reconstruct its evolution since 8.2 Ma. Two mechanisms for typical double BSRs in the Shenhu area are shown, and the relationship between the evolving thickness of the GHSZ and the dynamic accumulation of NGHs at typical stations in the Shenhu area is clarified. The results show that the thickness of the GHSZ varies over time with overall thickening in the Shenhu area. The current thickness of the GHSZ is between 160.98 and 267.94 m. Two mechanisms of double BSRs in the Shenhu area are summarized: the double BSRs pattern based on changes in formation temperature, pressure and other conditions and the double BSRs pattern based on differences in gas source and composition. The formation process and occurrence characteristics of double BSRs and hydrate at site SH-W07-2016 in the Shenhu area are also closely related to the changes in thickness of the GHSZ. In addition, the age when gas source first enters the GHSZ has a considerable influence on the dynamic accumulation process of hydrate. Since the formation of hydrate above the BSR at site SH-W07-2016, the GHSZ has experienced up to two periods of thickening and two periods of thinning at this site. With the changes in the thickness of the GHSZ, up to two stages of hydrate formation and at most two stages of hydrate decomposition have occurred. This paper is of great value for understanding the formation of multiple bottom-simulating reflectors (BSRs) as well as the migration, accumulation and dissipation of natural gas hydrate (NGH) during the dynamic accumulation process.
Analysis of Failure Behavior Based on the Ring Shear Test in a Bedding Rock Landslide of the Three Gorges Reservoir
Authors: Li Wei-na , Xu Guang-li , Yu Zhang
Published: April 2022

Complex geological environment and climatic conditions lead to frequent geological disasters in the Three Gorges Reservoir area. In particular, due to the impact of reservoir impoundment, a large number of landslides have occurred, resulting in huge economic losses and casualties. In this study, the bedding rock landslide is taken as the research object. First, the DTA-138 geotechnical ring shear apparatus system is used for the ring shear test. Second, a two-dimensional numerical model of Shanshucao landslide was established, and simulation was carried out. The main conclusions are as follows: 1) The shear stress–shear displacement curves of sliding zone soil under different shear rates show typical strain softening characteristics. 2) The shear rate–internal friction angle curve showed a good logarithmic relationship. 3) The fundamental reason for the rapid sliding into the river after the instability of the main sliding zone of the Shanshucao landslide is the negative rate effect of the argillized interlayer sliding zone soil in the main sliding zone.
Acoustoelastic FD Simulation of Elastic Wave Propagation in Prestressed Media
Authors: Yang Haidi , Fu Li-Yun , Fu Bo-Ye , Müller Tobias M.
Published: April 2022

Insights into wave propagation in prestressed media are important in geophysical applications such as monitoring changes in geo-pressure and tectonic stress. This can be addressed by acoustoelasticity theory, which accounts for nonlinear strain responses due to stresses of finite magnitude. In this study, a rotated staggered grid finite-difference (RSG-FD) method with an unsplit convolutional perfectly matched layer absorbing boundary is used to solve the relevant acoustoelastic equations with third-order elastic constants for elastic wave propagation in prestressed media. We partially verify our numerical simulations by the plane-wave theoretical solution. Comparisons of theoretical and calculated wave velocities are conducted for both P-wave and S-wave as a function of hydrostatic prestresses. We discuss several aspects of the numerical implementation. Numerical acoustoelasticity simulations for wave propagation in single- and double-layer models are carried out under four states of prestresses, confining, uniaxial, pure-shear, and simple-shear. The results display the effective anisotropy of elastic wave propagation in acoustoelastic media, illustrating that the prestress-induced velocity anisotropy is of orthotropic features strongly related to the orientation of prestresses. These examples demonstrate the significant impact of prestressed conditions on seismic responses in both phase and amplitude.
Association of Mild Thyroid Dysfunction and Adverse Prognosis Among Chinese Patients With Acute ST Segment Elevation Myocardial Infarction
Authors: Li Mei-Fang , Wei Ze-Tao , Li Shuai , Feng Qi-Ming , Li Jing-Bo
Published: April 2022

Aims

Thyroid hormones widely affect the cardiovascular system, but the effects of mild thyroid dysfunction on the clinical prognosis of patients with acute ST segment elevation myocardial infarction (STEMI) remains unclear. Our aims were to analyze the relations between mild thyroid dysfunction at admission and clinical outcomes in Chinese patients with STEMI.

Methods

A total of 1,176 STEMI patients with the available data of thyroid function and follow-up were analyzed, including 348 patients with mild thyroid dysfunction [subclinical hypothyroidism (n=81), hyperthyroidism (SHyper) (n=51), and low triiodothyronine syndrome (LT3S) (n=216)] and 828 patients with euthyroid function. During a median 4.4-year follow-up, in-hospital mortality, cardiac and all-cause mortalities were subsequently compared among the four groups.

Results

Compared with the euthyroid group, STEMI patients in the SHyper and LT3S groups faced obviously increased risks of in-hospital death [odds ratio (OR): 5.007, 95% confidence interval (CI): 1.246–20.124, p = 0.023 and OR: 2.491, 95% CI: 1.054–5.887, p = 0.037, respectively) even after adjustment for various confounding factors. During a median 4.4-year follow-up, STEMI patients with LT3S at baseline had higher cardiovascular mortality [hazard ratio (HR): 1.880, 95% CI: 1.178–2.998, p = 0.008] and all-cause mortality HR: 1.647, 95% CI: 1.072–2.531, p = 0.023] than those with euthyroid at baseline, whereas no significantly increased mortality was found for STEMI patients with SCH and SHyper at baseline.

Conclusions

STEMI patients with SHyper at admission had increased risk of in-hospital mortality, and STEMI patients with LT3S at baseline had worse prognosis and higher incidences of in-hospital mortality and cardiovascular and all-cause deaths compared with euthyroid patients.
Estrogenic Pastures: A Source of Endocrine Disruption in Sheep Reproduction
Authors: Pool Kelsey R. , Chazal Faustine , Smith Jeremy T. , Blache Dominique
Published: April 2022

Phytoestrogens can impact on reproductive health due to their structural similarity to estradiol. Initially identified in sheep consuming estrogenic pasture, phytoestrogens are known to influence reproductive capacity in numerous species. Estrogenic pastures continue to persist in sheep production systems, yet there has been little headway in our understanding of the underlying mechanisms that link phytoestrogens with compromised reproduction in sheep. Here we review the known and postulated actions of phytoestrogens on reproduction, with particular focus on competitive binding with nuclear and non-nuclear estrogen receptors, modifications to the epigenome, and the downstream impacts on normal physiological function. The review examines the evidence that phytoestrogens cause reproductive dysfunction in both the sexes, and that outcomes depend on the developmental period when an individual is exposed to phytoestrogen.
Immune Cells as Critical Regulators of Steroidogenesis in the Testis and Beyond
Authors: Gu Xiaowei , Li Shu-Yun , Matsuyama Satoko , DeFalco Tony
Published: April 2022

Steroidogenesis is an essential biological process for embryonic development, reproduction, and adult health. While specific glandular cells, such as Leydig cells in the testis, are traditionally known to be the principal players in steroid hormone production, there are other cell types that contribute to the process of steroidogenesis. In particular, immune cells are often an important component of the cellular niche that is required for the production of steroid hormones. For several decades, studies have reported that testicular macrophages and Leydig cells are intimately associated and exhibit a dependency on the other cell type for their proper development; however, the mechanisms that underlie the functional relationship between macrophages and Leydig cells are unclear. Beyond the testis, in certain instances immune cells themselves, such as certain types of lymphocytes, are capable of steroid hormone production, thus highlighting the complexity and diversity that underlie steroidogenesis. In this review we will describe how immune cells are critical regulators of steroidogenesis in the testis and in extra-glandular locations, as well as discuss how this area of research offers opportunities to uncover new insights into steroid hormone production.
Multi-Source Data Processing and Fusion Method for Power Distribution Internet of Things Based on Edge Intelligence
Authors: Yuan Quande , Pi Yuzhen , Kou Lei , Zhang Fangfang , Li Yang , Zhang Zhenming
Published: April 2022

With the rapid advancement of the Energy Internet strategy, the number of sensors within the Power Distribution Internet of Things (PD-IoT) has increased dramatically. In this study, an edge intelligence-based PD-IoT multi-source data processing and fusion method is proposed to solve the problems of confusing storage and insufficient fusion computing performance of multi-source heterogeneous distribution data. First, a PD-IoT multi-source data processing and fusion architecture based on edge smart terminals is designed. Second, the multi-source sensor data in the distribution network is unified in dimension and magnitude. By introducing the Box–Cox transform to improve the data offset problem in the Z-score normalization process, a multi-source heterogeneous data processing method for distribution networks based on the Box–Cox transform Z-score is proposed. Then, the conflicting phenomena of DS inference methods in data source fusion are optimally handled based on the PCA algorithm. A multi-source data fusion model based on DS inference with conflict optimization is constructed to ensure the effective fusion of distribution data sources from different domains. Finally, the effectiveness of the proposed method is verified by an experimental analysis of an IEEE39 node system in a regional distribution network in China.
Formation of Solonchak in the Area of the Discharged Ancient Brine Wells (Perm Krai, Russia)
Authors: Khayrulina Elena , Mitrakova Natalya , Poroshina Natalya , Menshikova Elena , Perminova Anna
Published: April 2022

The change in soil-forming processes and, as a result, in the ecosystem due to nearly 300-year long outflow of highly saline waters from ancient brine wells is considered for Perm Krai in Russia for the first time. The study area is located in the high floodplain of the Usolka River valley. Sodium-chloride ancient brine wells with mineralization of about 30 g/L flow in streams over the soil surface and enter the Usolka River. The paper considers three soil types at various distances from a saline stream. The main pedogenic processes are the sod-forming process and gleying in alluvial soils. Soils in Gleyic Fluvisols (background)—Gleyic Fluvisols (Sulfatic) (transition)—Solonchak (affected by sodium-chloride brines) series were studied in terms of occurring soil-forming processes. All studied soils are formed under hydromorphic conditions. It is evidenced by gleization. However, the morphological and physicochemical properties of the soils differ. The presence of water-soluble ions in the solonchak suggests that salinization is occurring. The sum of toxic salts was 0.94% which was several times higher than in the transition and background soils. The sodium adsorption ratio (SAR) ranged from 10.4 to 21.6, with a рН of 8.3–9.1. The saline soils were more alkaline (pH average 8.8 and 9.3) than the background soil (pH 8.1). SAR decreased significantly in the Solonchak—transition—background soil series from 16.9 to 0.7. The aforementioned observations, as well as physical properties of the saline soil, clearly show the entry of sodium into the solonchak adsorption complex, indicating the solonization process. The study area is characterized by the presence of salt-tolerant species of herbaceous plants and an obligate halophyte. Salicornia perennans Willd, a halophyte, was discovered in the wells’ discharge area at a distance of 0.2–1.5 m from saline streams. The analysis of the long-term impact of highly mineralized waters on the natural environment will aid in revealing and forecasting ecosystem changes caused by potash mining in Perm Krai for environmental risk assessment for new and existing potash enterprises.
Barriers and Enablers to the Regulation of Sanitation Services: A Framework for Emptying and Transport Services in Sub-Saharan African Cities
Authors: Lerebours Alix , Scott Rebecca , Sansom Kevin , Kayaga Sam
Published: April 2022

Onsite sanitation is the dominant form of sanitation in Sub-Saharan African cities. Services for emptying the fecal sludge from these facilities and transporting it to safe disposal or treatment plants are crucial to public and environmental health. While these services are becoming increasingly regulated, implementation of the regulation remains a challenge. Through a multiple-case study anchored in the Contextual Interaction Theory, this research investigated the barriers and enablers to regulating emptying and transport services for fecal sludge. Looking at the cases of Kampala, Lusaka, and Freetown, this research found that both the content of the regulation and the regulatory process (initiation, creation or reform through to implementation) play a key role in the extent to which the regulation is or can be implemented. New elements relating to the knowledge, motivation, and resources of all stakeholders are identified as crucial to achieve regulated services. The findings have resulted in a framework that identifies the key elements to consider when regulating services. This framework would prove useful to practitioners and researchers engaged through all stages of creating, implementing, and evaluating regulatory practices.
Genotyping-by-Sequencing Reveals the Impact of Restocking on Wild Common Carp Populations of the Southern Caspian Basin
Authors: Jafari Omid , Zeinalabedini Mehrshad , Robledo Diego , Fernandes Jorge M. O. , Hedayati Ali-Akbar , Arefnezhad Babak
Published: April 2022

Understanding the population structure and level of genetic diversity of wild populations is fundamental for appropriate stock management and species conservation. The common carp (Cyprinus carpio) is one of the most important bony fish throughout the Southern coastline of the Caspian Sea, but captures of this species have seen a dramatic reduction during the last decade. As a consequence, a restocking program has been put in place to maintain C. carpio populations, but its impact is not clear. In the present study, the population structure and genetic diversity of C. carpio in the Southern Caspian basin was determined using 17,828 single-nucleotide polymorphism (SNP) markers. A total of 117 individuals collected from four different locations in the southern Caspian basin and a farm were genotyped by genotyping-by-sequencing. The overall Fst obtained was 0.04, indicating a low level of differentiation between populations, and most genetic diversity was attributed to within population variation (97%). The low Fst values suggest that frequent migration events between different locations occur, and three migration events were inferred in the present study. However, each population still showed a distinct genetic profile, which allowed distinguishing the origin of the fish. This indicates that the ongoing restocking program is maintaining the differences between populations to some extent. Nonetheless, high inbreeding and low heterozygosity were detected in all populations, suggesting that additional conservation efforts are required to protect C. carpio populations in the Southern coast of the Caspian Sea.
The Impact of Digital Inclusive Finance on Agricultural Green Total Factor Productivity: Evidence From China
Authors: Gao Qiang , Cheng Changming , Sun Guanglin , Li Jianfeng
Published: April 2022

This manuscript applies the GML model with unexpected output to measure agricultural green total factor productivity (GTFP) in 30 provinces in China from 2011 to 2019. We explore the effect and mechanism of digital inclusive finance (DIF) on agricultural green total factor productivity. Our empirical results show that during the sample period, China’s agricultural green total factor productivity has shown an increasing trend. Digital inclusive finance mainly promotes agricultural GTFP by improving green technology level. The coverage rate, the application rate and the digitalization rate of digital inclusive finance all generate positive effects on agricultural green total factor productivity, among which the coverage rate contributes the most. Besides, the positive effect of digital inclusive finance in the eastern coastal areas is more significant than in other areas. The analysis of the mechanism shows that digital inclusive finance can indirectly help improve agricultural green total factor productivity through motivating agricultural technology innovation and industrial structure optimization. The research results of this manuscript are extremely meaningful for better implement DIF-related policies, and promote the green development of agriculture.
The Genetic and Clinical Outcomes in Fetuses With Isolated Fetal Growth Restriction: A Chinese Single-Center Retrospective Study
Authors: Zhou Hang , Cheng Ken , Li Yingsi , Fu Fang , Li Ru , Zhang Yongling , Yang Xin , Jing Xiangyi , Li Fucheng , Han Jin , Pan Min , Zhen Li , Li Dongzhi , Liao Can
Published: April 2022

Objective: To evaluate the utility of a chromosomal microarray (CMA) in fetuses with isolated fetal growth restriction (FGR) and explore risk factors for the prediction of chromosomal aberration and perinatal adverse outcomes.

Method: This study included 271 fetuses of estimated fetal weight less than the 3rd percentile without other structural malformation. Early-onset and late-onset FGR were defined as gestational weeks less than 32 weeks and more than 32 weeks respectively. These patients underwent quantitative fluorescent polymerase chain reaction (QF-PCR) and CMA as the first-line genetic detection strategy. Chromosomal anomalies were compared after stratified analysis by the early-onset and the late-onset FGR, including the absence or presence of ultrasound soft markers, abnormal amniotic fluid, abnormal umbilical Doppler, and gestational disorders. The follow-up time was within 1 year after birth. Logistic regression was used to seek risk predictors of chromosomal aberration and perinatal adverse outcomes for isolated FGR.

Results: The CMA identified clinically significant variants in 18/271 (6.6%) fetuses, and variants of unknown significance (VOUS) in 15/271 (5.5%) fetuses. Stratified analysis showed that there was a higher incidence of clinically significant variants in fetuses with the early-onset FGR compared with late-onset FGR (8.7%, 17/195 vs. 1.3%, 1/76, p < 0.05). Regression analysis showed that early gestational age (GA) at diagnosis of FGR was the major risk factor for chromosomal aberration (OR = 0.846). By variable regression analysis, early GA at diagnosis and decreased estimated fetal weight (EFW) percentile of suspicion of FGR, asymmetrical FGR, abnormal amniotic fluid, and severe preeclampsia could all increase the risk of adverse outcomes of isolated FGR including intra-uterine fetal death (IUFD), termination of pregnancy (TOP), and preterm birth in pregnancies with FGR.

Conclusion: This study emphasized the value of microarrays for unbalanced genomic variants in fetuses with isolated FGR, especially since the gestational age of nullipara was less than 32 weeks. Perinatal adverse outcomes of isolated FGR were influenced by multiple factors including GA and estimated fetal weight (EFW) percentile of suspicion of FGR, asymmetrical FGR, abnormal amniotic fluid, and severe preeclampsia.
Histone Modifications, Internucleosome Dynamics, and DNA Stresses: How They Cooperate to “Functionalize” Nucleosomes
Authors: Krajewski Wladyslaw A.
Published: April 2022

Tight packaging of DNA in chromatin severely constrains DNA accessibility and dynamics. In contrast, nucleosomes in active chromatin state are highly flexible, can exchange their histones, and are virtually “transparent” to RNA polymerases, which transcribe through gene bodies at rates comparable to that of naked DNA. Defining mechanisms that revert nucleosome repression, in addition to their value for basic science, is of key importance for the diagnosis and treatment of genetic diseases. Chromatin activity is largely regulated by histone posttranslational modifications, ranging from small chemical groups up to the yet understudied “bulky” ubiquitylation and sumoylation. However, it is to be revealed how histone marks are “translated” to permissive or repressive changes in nucleosomes: it is a general opinion that histone modifications act primarily as “signals” for recruiting the regulatory proteins or as a “neutralizer” of electrostatic shielding of histone tails. Here, we would like to discuss recent evidence suggesting that histone ubiquitylation, in a DNA stress–dependent manner, can directly regulate the dynamics of the nucleosome and their primary structure and can promote nucleosome decomposition to hexasome particles or additionally stabilize nucleosomes against unwrapping. In addition, nucleosome repression/ derepression studies are usually performed with single mononucleosomes as a model. We would like to review and discuss recent findings showing that internucleosomal interactions could strongly modulate the dynamics and rearrangements of nucleosomes. Our hypothesis is that bulky histone modifications, nucleosome inherent dynamics, internucleosome interactions, and DNA torsions could act in cooperation to orchestrate the formation of different dynamic states of arrayed nucleosomes and thus promote chromatin functionality and diversify epigenetic programming methods.
Inhibitory Effect of FMRFamide on NO Production During Immune Defense in Sepiella japonica
Authors: Zheng Libing , Cao Huimin , Qiu Jiayin , Chi Changfeng
Published: April 2022

Neuropeptide Phe-Met-Arg-Phe-NH2 (FMRFamide), specifically existing in invertebrates, plays pivotal roles in various physiological processes. The involvement in neuroendocrine-immune regulation was explored in recent years, and it could modulate nitric oxide (NO) production under immune stress. However, detailed knowledge is still little known. In this study, we identified FMRFamide as an inhibitory factor on NO production in the immune reaction of Sepiella japonica. Firstly, Vibrio harveyi incubation caused significantly upregulated expression of FMRFamide precursor and NO synthase (NOS) in just hatched cuttlefish with quantitative Real-time PCR (qRT-PCR), which indicated that both were likely to be involved in the immune defense. The whole-mount in situ hybridization (ISH) detected FMRFamide precursor and NOS-positive signals appeared colocalization, suggesting that at histological and anatomical levels FMRFamide might interact with NOS. Next, NOS mRNA was highly significantly upregulated at 72 h when FMRFamide precursor mRNA was knocked down effectively with the RNA interference (RNAi) method; the results hinted that FMRFamide was likely to regulate NO production. Continuously, the inflammatory model was constructed in RAW 264.7 cells induced by lipopolysaccharide (LPS), FMRFamide administration resulted in a highly significant reduction of the NO level in dose- and time-response manners. Although the addition of the selected inducible NOS (iNOS) inhibitor had inhibited the NO production induced by LPS, the additional FMRFamide could still furtherly sharpen the process. Collectively, it was concluded that neuropeptide FMRFamide could indeed inhibit NO production to serve as feedback regulation at the late stage of immune response to protect hosts from excessive immune cytotoxicity. The inhibitory effect on NO production could not only be mediated by the NOS pathway but also be implemented through other pathways that needed to be furtherly explored. The results will provide data for comparing the structure and immune function of neuroendocrine-immune system (NEIS) between “advanced” cephalopods and other invertebrates and will provide new information for understanding the NEIS of cephalopods.
Variants Disrupting CD40L Transmembrane Domain and Atypical X-Linked Hyper-IgM Syndrome: A Case Report With Leishmaniasis and Review of the Literature
Authors: Palterer Boaz , Salvati Lorenzo , Capone Manuela , Mecheri Valentina , Maggi Laura , Mazzoni Alessio , Cosmi Lorenzo , Volpi Nila , Tiberi Lucia , Provenzano Aldesia , Giglio Sabrina , Parronchi Paola , Maggiore Giandomenico , Gallo Oreste , Bartoloni Alessandro , Annunziato Francesco , Zammarchi Lorenzo , Liotta Francesco
Published: April 2022

X-linked hyper-IgM (XHIGM) syndrome is caused by mutations of the CD40LG gene, encoding the CD40L protein. The clinical presentation is characterized by early-onset infections, with profound hypogammaglobulinemia and often elevated IgM, susceptibility to opportunistic infections, such asPneumocystis jiroveciipneumonia, biliary tract disease due toCryptosporidium parvum, and malignancy. We report a 41-year-old male presenting with recurrent leishmaniasis, hypogammaglobulinemia, and myopathy. Whole-exome sequencing (WES) identified a missense variant in the CD40LG gene (c.107T>A, p.M36K), involving the transmembrane domain of the protein and a missense variant in the carnitine palmitoyl-transferase II (CPT2; c.593C>G; p.S198C) gene, leading to the diagnosis of hypomorphic XHIGM and CPT2 deficiency stress-induced myopathy. A review of all the previously reported cases of XHIGM with variants in the transmembrane domain showcased that these patients could present with atypical clinical features. Variants in the transmembrane domain of CD40LG act as hypomorphic generating a protein with a lower surface expression. Unlike large deletions or extracellular domain variants, they do not abolish the interaction with CD40, therefore preserving some biological activity.
Short Term Isocaloric Ketogenic Diet Modulates NLRP3 Inflammasome Via B-hydroxybutyrate and Fibroblast Growth Factor 21
Authors: Kim Eun Ran , Kim So Ra , Cho Wonhee , Lee Sang-Guk , Kim Soo Hyun , Kim Jin Hee , Choi Eunhye , Kim Jeong-Ho , Yu Je-Wook , Lee Byung-Wan , Kang Eun Seok , Cha Bong-Soo , Lee Myung-Shik , Cho Jin Won , Jeon Justin Y. , Lee Yong-ho
Published: April 2022

A ketogenic diet (KD) is known to have beneficial health effects. Various types of KD interventions have been applied to manage metabolic syndrome based on modification of diet parameters such as duration of intervention, macronutrient components, and total calories. Nevertheless, the beneficial health impact of isocaloric KD is largely unknown, especially in healthy subjects. The present study investigated the acute effects of a 3-day isocaloric KD. In this non-randomized intervention study, we recruited 15 healthy volunteers aged 24-38 years (7 men and 8 women) and placed them on an isocaloric KD restricting intake of carbohydrates but not energy (75% fat, 20% protein, 5% carbohydrate) for 3 days. Biochemical profiles and laboratory measurements were performed. Peripheral blood monocular cells were cultured, and measured cell stimulated cytokines. After short-term isocaloric KD, subjects lost body weight and serum free fatty acid levels were increased. These results accompanied elevated serum β-hydroxybutyrate (BHB) concentration and fibroblast growth factor 21 (FGF21) levels and improved insulin sensitivity. Regarding the direct effect of BHB on inflammasome activation, interleukin-1β (IL-1β) and tumor necrosis factor-α secretion in response to adenosine triphosphate or palmitate stimulation in human macrophages decreased significantly after isocaloric KD. In ex-vivo experiments with macrophages, both FGF21 and BHB further reduced IL-1β secretion compared to either BHB or FGF21 alone. The inhibitory effect of FGF21 on IL-1β secretion was blunted with bafilomycin treatment, which blocked autophagy flux. In conclusion, isocaloric KD for 3 days is a promising approach to improve metabolic and inflammatory status.

Clinical Trial Registration

clinicaltrials.gov (NCT02964572).