bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative Study on the Efficiency of Mercury Removal From Wastewater Using Bacterial Cellulose Membranes and Their Oxidized Analogue
Authors: Suárez-Avendaño D. , Martínez-Correa E. , Cañas-Gutierrez A. , Castro-Riascos M. , Zuluaga-Gallego R. , Gañán-Rojo P. , Peresin M. , Pereira M. , Castro-Herazo C.
Published: March 2022

A comparative study was conducted on the efficiency of mercury removal using bacterial nanocellulose (BNC) membranes obtained from the fermentation of the microorganism Komagataeibacter medellinensis, in contrast with its oxidized analog obtained by modifying the bacterial nanocellulose membranes via oxidation with 2,2,6,6-Tetramethylpiperidine-1-oxyl. Both types of membranes (modified and unmodified) were characterized to identify variations in the Physico-chemical parameters after modification. FTIR spectra confirmed the chemical modification of cellulose in all reaction conditions by the presence of a new characteristic band at ∼1730 cm−1, corresponding to the new carboxylic groups produced by the oxidative process, and the decline of the band at ∼1,650 cm−1, corresponding to the hydroxyl groups of the C6 carbon. While the XRD profiles indicated that the percentage of BNC crystallinity decreased and the SEM images showed that the nanoribbon network was interrupted as the amount of oxidizing agent increased. The kinetics of mercury removal from both types of membrane was evaluated by calculating the concentration of mercury at different times and establishing a mathematical model to describe the kinetics of this process. The modified membranes improved significantly the adsorption process of the metal ion and it was found that the modification that results in the greatest adsorption efficiency was BNC-m 7.5 with a value of 92.97%. The results obtained suggest that the modification of the bacterial nanocellulose membranes by oxidation transcendentally improves the mercury removal capacity, outlining the modified membranes as an excellent material for mercury removal in wastewater.
Evaluation of Additional Drosophila suzukii Male-Only Strains Generated Through Remobilization of an FL19 Transgene
Authors: Yamamoto Akihiko , Yadav Amarish K. , Scott Maxwell J.
Published: March 2022

Drosophila suzukii (D. suzukii) (Matsumura, 1931; Diptera: Drosophilidae), also known as spotted wing Drosophila, is a worldwide pest of fruits with soft skins such as blueberries and cherries. Originally from Asia, D. suzukii is now present in the Americas and Europe and has become a significant economic pest. Growers largely rely on insecticides for the control of D. suzukii. Genetic strategies offer a species-specific environmentally friendly way for suppression of D. suzukii populations. We previously developed a transgenic strain of D. suzukii that produced only males on a diet that did not contain tetracycline. The strain carried a single copy of the FL19 construct on chromosome 3. Repeated releases of an excess of FL19 males led to suppression of D. suzukii populations in laboratory cage trials. Females died as a consequence of overexpression of the tetracycline transactivator (tTA) and tTA-activated expression of the head involution defective proapoptotic gene. The aim of this study was to generate additional male-only strains that carried two copies of the FL19 transgene through crossing the original line with a piggyBac jumpstarter strain. Males that carried either two chromosome 3 or a singleX-linked transgene were identified through stronger expression of the red fluorescent protein marker gene. The brighter fluorescence of the X-linked lines was likely due to dosage compensation of the red fluorescent protein gene. In total, four X-linked lines and eleven lines with two copies on chromosome 3 were obtained, of which five were further examined. All but one of the strains produced only males on a diet without tetracycline. When crossed with wild type virgin females, all of the five two copy autosomal strains examined produced only males. However, the single copy X-linked lines did not show dominant female lethality. Five of the autosomal lines were further evaluated for productivity (egg to adult) and male competition. Based on these results, the most promising lines have been selected for future population suppression experiments with strains from different geographical locations.
Caspase-8 Deficient Osteoblastic Cells Display Alterations in Non-Apoptotic Pathways
Authors: Vesela Barbora , Killinger Michael , Rihova Kamila , Benes Petr , Svandová Eva , Kratochvilová Adela , Trcka Filip , Kleparnik Karel , Matalova Eva
Published: March 2022

Caspase-8 is the key component of the receptor-mediated (extrinsic) apoptotic pathway. Immunological localization of active caspase-8 showed its presence in osteoblasts, including non-apoptotic ones. Further in vivo exploration of caspase-8 functions in the bone is hindered by the fact that the caspase-8 knock-out is lethal prenatally. Examinations were thus performed using individual cell populations in vitro. In this study, caspase-8 was eliminated by the CRISPR/cas9 technology in MC3T3-E1 cells, the most common in vitro model of osteoblastic populations. The aim of the work was to specify the consequences of caspase-8 deficiency on non-apoptotic pathways. The impact on the osteogenic gene expression of the osteoblastic cells along with alterations in proliferation, caspase cascades and rapamycin induced autophagy response were evaluated. Osteogenic differentiation of caspase-8 deficient cells was inhibited as these cells displayed a decreased level of mineralization and lower activity of alkaline phosphatase. Among affected osteogenic genes, based on the PCR Array, major changes were observed for Ctsk, as down-regulated, and Gdf10, as up-regulated. Other significantly down-regulated genes included those coding osteocalcin, bone morphogenetic proteins (-3, -4 and -7), collagens (-1a1, -14a1) or Phex. The formation of autophagosomes was not altered in rapamycin-treated caspase-8 deficient cells, but expression of some autophagy-related genes, including Tnfsf10, Cxcr4, Dapk1 and Igf1, was significantly downregulated. These data provide new insight into the effects of caspase-8 on non-apoptotic osteogenic pathways.
The Protective Effects of γ-Tocotrienol on Muscle Stem Cells Through Inhibiting Reactive Oxidative Stress Production
Authors: Yang Shuo , Yang Juan , Zhao Huiwen , Deng Rong , Fan Hancheng , Zhang Jinfu , Yang Zihao , Zeng Huihong , Kuang Bohai , Shao Lijian
Published: March 2022

Pseudotrophic muscular dystrophy is a common clinical skeletal muscle necrotic disease, among which Duchenne muscular dystrophy (DMD) is the predominant. For such diseases, there is no clinically effective treatment, which is only symptomatic or palliative treatment. Oxidative stress and chronic inflammation are common pathological features of DMD. In recent years, it has been found that the pathophysiological changes of skeletal muscle in DMD mice are related to muscle stem cell failure. In the present study, we established a DMD mice model and provided tocotrienol (γ-tocotrienol, GT3), an antioxidant compound, to explore the relationship between the physiological state of muscle stem cells and oxidative stress. The results showed that the application of GT3 can reduce ROS production and cellular proliferation in the muscle stem cells of DMD mice, which is beneficial to promote the recovery of muscle stem cell function in DMD mice. GT3 treatment improved the differentiation ability of muscle stem cells in DMD mice with increasing numbers of MyoD+ cells. GT3 application significantly decreased percentages of CD45+ cells and PDGFRα+ fibro-adipogenic progenitors in the tibialis anterior of DMD mice, indicating that the increased inflammation and fibro-adipogenic progenitors were attenuated in GT3-treated DMD mice. These data suggest that increased ROS production causes dysfunctional muscle stem cell in DMD mice, which might provide a new avenue to treat DMD patients in the clinic.
Nicotinic Acid Adenine Dinucleotide Phosphate Induces Intracellular Ca2+ Signalling and Stimulates Proliferation in Human Cardiac Mesenchymal Stromal Cells
Authors: Faris Pawan , Casali Claudio , Negri Sharon , Iengo Lara , Biggiogera Marco , Maione Angela Serena , Moccia Francesco
Published: March 2022

Nicotinic acid adenine dinucleotide phosphate (NAADP) is a newly discovered second messenger that gates two pore channels 1 (TPC1) and 2 (TPC2) to elicit endo-lysosomal (EL) Ca2+ release. NAADP-induced lysosomal Ca2+ release may be amplified by the endoplasmic reticulum (ER) through the Ca2+-induced Ca2+ release (CICR) mechanism. NAADP-induced intracellular Ca2+ signals were shown to modulate a growing number of functions in the cardiovascular system, but their occurrence and role in cardiac mesenchymal stromal cells (C-MSCs) is still unknown. Herein, we found that exogenous delivery of NAADP-AM induced a robust Ca2+ signal that was abolished by disrupting the lysosomal Ca2+ store with Gly-Phe β-naphthylamide, nigericin, and bafilomycin A1, and blocking TPC1 and TPC2, that are both expressed at protein level in C-MSCs. Furthermore, NAADP-induced EL Ca2+ release resulted in the Ca2+-dependent recruitment of ER-embedded InsP3Rs and SOCE activation. Transmission electron microscopy revealed clearly visible membrane contact sites between lysosome and ER membranes, which are predicted to provide the sub-cellular framework for lysosomal Ca2+ to recruit ER-embedded InsP3Rs through CICR. NAADP-induced EL Ca2+ mobilization via EL TPC was found to trigger the intracellular Ca2+ signals whereby Fetal Bovine Serum (FBS) induces C-MSC proliferation. Furthermore, NAADP-evoked Ca2+ release was required to mediate FBS-induced extracellular signal-regulated kinase (ERK), but not Akt, phosphorylation in C-MSCs. These finding support the notion that NAADP-induced TPC activation could be targeted to boost proliferation in C-MSCs and pave the way for future studies assessing whether aberrant NAADP signaling in C-MSCs could be involved in cardiac disorders.
Global Threat of Carbapenem-Resistant Gram-Negative Bacteria
Authors: Jean Shio-Shin , Harnod Dorji , Hsueh Po-Ren
Published: March 2022

Infections caused by multidrug-resistant (MDR) and extensively drug-resistant (XDR) Gram-negative bacteria (GNB), including carbapenem-resistant (CR) Enterobacterales (CRE; harboring mainly blaKPC, blaNDM, and blaOXA-48-like genes), CR- or MDR/XDR-Pseudomonas aeruginosa (production of VIM, IMP, or NDM carbapenemases combined with porin alteration), and Acinetobacter baumannii complex (producing mainly OXA-23, OXA-58-like carbapenemases), have gradually worsened and become a major challenge to public health because of limited antibiotic choice and high case-fatality rates. Diverse MDR/XDR-GNB isolates have been predominantly cultured from inpatients and hospital equipment/settings, but CRE has also been identified in community settings and long-term care facilities. Several CRE outbreaks cost hospitals and healthcare institutions huge economic burdens for disinfection and containment of their disseminations. Parenteral polymyxin B/E has been observed to have a poor pharmacokinetic profile for the treatment of CR- and XDR-GNB. It has been determined that tigecycline is suitable for the treatment of bloodstream infections owing to GNB, with a minimum inhibitory concentration of ≤ 0.5 mg/L. Ceftazidime-avibactam is a last-resort antibiotic against GNB of Ambler class A/C/D enzyme-producers and a majority of CR-P. aeruginosa isolates. Furthermore, ceftolozane-tazobactam is shown to exhibit excellent in vitro activity against CR- and XDR-P. aeruginosa isolates. Several pharmaceuticals have devoted to exploring novel antibiotics to combat these troublesome XDR-GNBs. Nevertheless, only few antibiotics are shown to be effective in vitro against CR/XDR-A. baumannii complex isolates. In this era of antibiotic pipelines, strict implementation of antibiotic stewardship is as important as in-time isolation cohorts in limiting the spread of CR/XDR-GNB and alleviating the worsening trends of resistance.
Gut Microbiota-Related Inflammation Factors as a Potential Biomarker for Diagnosing Major Depressive Disorder
Authors: Bai Shunjie , Bai Huili , Li Detao , Zhong Qi , Xie Jing , Chen Jian-jun
Published: March 2022

Objective

Although many works have been done, the objectively measured diagnostic biomarkers are not available. Thus, we conducted this study to identify potential biomarkers for objectively diagnosing depression and explore the role of gut microbiota in the onset of depression.

Methods

Major depressive disorder (MDD) patients (n=56) and demographic data-matched healthy controls (HCs) (n=56) were included in this study. The gut microbiota in fecal samples and inflammation-related factors in serum were measured. Both univariate and multivariate statistical analyses were performed to identify the differential gut microbiota and inflammation-related factors.

Results

Finally, 46 differential operational taxonomic units (OTUs) (60.9% OTUs belonging to Firmicutes) and ten differential inflammation-related factors were identified. Correlation analysis showed that there were significant correlations between 14 differential OTUs (9 OTUs belonging to Firmicutes and 5 OTUs belonging to family Lachnospiraceae under Firmicutes) and seven differential inflammation-related factors. Meanwhile, 14 differential OTUs (9 OTUs belonging to Firmicutes and 5 OTUs belonging to family Lachnospiraceae under Firmicutes) and five differential inflammation-related factors (adiponectin, apolipoprotein A1, alpha 1-antitrypsin, neutrophilicgranulocyte count/white blood cell count and basophil count) were significantly correlated to depression severity. A panel consisting of these five differential inflammation-related factors could effectively diagnose MDD patients from HCs.

Conclusions

Our results suggested that Firmicutes, especially family Lachnospiraceae, might play a role in the onset of depression via affecting the inflammation levels of host, and these five differential inflammation-related factors could be potential biomarkers for objectively diagnosing MDD.
Comparative Analysis of Gut Microbiota in Centenarians and Young People: Impact of Eating Habits and Childhood Living Environment
Authors: Sepp Epp , Smidt Imbi , Rööp Tiiu , Štšepetova Jelena , Kõljalg Siiri , Mikelsaar Marika , Soidla Indrek , Ainsaar Mare , Kolk Helgi , Vallas Mirjam , Jaagura Madis , Mändar Reet
Published: March 2022

The composition of centenarians’ gut microbiota has consistently been used as a model for healthy aging studies. However, there is an incomplete understanding of how childhood living conditions and eating habits affect the development and composition of gastrointestinal microbiota in centenarians with good cognitive functions. We compared the gut microbiota as well as the living and eating habits of the oldest-old group and the young people group. The richness and diversity of microbiota and the abundance of hereditary and environmental microbes were higher in people with longevity than young people. People with longevity ate more potatoes and cereal products. In their childhood, they had more exposure to farm animals and did not have sewers compared with young people. Young people’s gut microbiota contained more butyrate-producing bacteria and bacteria that characterized an animal-based Western diet. These results expand our understanding of the effects of childhood environment and diet on the development and stability of the microbiota in people with longevity.
The Effect of Blood Pressure Variability on Coronary Atherosclerosis Plaques
Authors: Liu Yue , Luo Xing , Jia Haibo , Yu Bo
Published: March 2022

Hypertension is one of the most important risk factors for coronary heart disease (CHD). The regulation of blood pressure plays a significant role in the development and prognosis of CHD. Blood pressure variability (BPV) refers to the degree of fluctuation of blood pressure over a period of time and is an important indicator of blood pressure stability. Blood pressure fluctuations are complex physiological phenomena, being affected by physiological and pharmacological effects and regulated by behavioral, environmental, hydrodynamic, and neural factors. According to the different time periods for measuring BPV, it can be divided into very short-term, short-term, mid-term, and long-term. Multiple cardiovascular disease animal models and clinical experiments have consistently indicated that abnormal BPV is closely related to coronary events and is a risk factor for CHD independently of average blood pressure. Thrombosis secondary to plaque rupture (PR) or plaque erosion can cause varying blood flow impairment, which is the main pathological basis of CHD. Plaque morphology and composition can influence the clinical outcome, treatment, and prognosis of patients with CHD. Research has shown that PR is more easily induced by hypertension. After adjusting for the traditional factors associated with plaque development, in recent years, some new discoveries have been made on the influence of abnormal BPV on the morphology and composition of coronary plaques and related mechanisms, including inflammation and hemodynamics. This article reviews the impact of BPV on coronary plaques and their related mechanisms, with a view to prevent the occurrence and development of CHD by controlling BPV and to provide new prevention and treatment strategies for the clinical treatment of abnormal blood pressure.
Social Determinants of Disparities in Mortality Outcomes in Congenital Heart Disease: A Systematic Review and Meta-Analysis
Authors: Tran Richard , Forman Rebecca , Mossialos Elias , Nasir Khurram , Kulkarni Aparna
Published: March 2022

Background

Social determinants of health (SDoH) affect congenital heart disease (CHD) mortality across all forms and age groups. We sought to evaluate risk of mortality from specific SDoH stratified across CHD to guide interventions to alleviate this risk.

Methods

We searched electronic databases between January 1980 and June 2019 and included studies that evaluated occurrence of CHD deaths and SDoH in English articles. Meta-analysis was performed if SDoH data were available in >3 studies. We included race/ethnicity, deprivation, insurance status, maternal age, maternal education, single/multiple pregnancy, hospital volume, and geographic location of patients as SDoH. Data were pooled using random-effects model and outcome was reported as odds ratio (OR) with 95% confidence interval (CI).

Results

Of 17,716 citations reviewed, 65 met inclusion criteria. Sixty-three were observational retrospective studies and two prospective. Of 546,981 patients, 34,080 died. Black patients with non-critical CHD in the first year of life (Odds Ratio 1.62 [95% confidence interval 1.47–1.79], I2 = 7.1%), with critical CHD as neonates (OR 1.27 [CI 1.05-1.55], I2 = 0%) and in the first year (OR 1.68, [1.45-1.95], I2 = 0.3%) had increased mortality. Deprived patients, multiple pregnancies, patients born to mothers <18 years and with education <12 years, and patients on public insurance with critical CHD have greater likelihood of death after the neonatal period.

Conclusion

This systematic review and meta-analysis found that Black patients with CHD are particularly vulnerable for mortality. Numerous SDoH that affect mortality were identified for specific time points in CHD course that may guide interventions, future research and policy.

Systematic Review Registration

[https://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42019139466&ID=CRD42019139466], identifier [CRD42019139466].
Ticagrelor vs. Clopidogrel in Older Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: Insights From a Real-World Registry
Authors: Zhang Yunnan , Peng Wenxing , Shi Xiujin , Han Jialun , Wang Yifan , Fang Zhenwei , Lin Yang
Published: March 2022

Background and Objectives

It is unclear whether more potent P2Y12 inhibitors are of benefit to older patients who are at high risk for both ischemia and bleeding. We conducted an observational study to compare the clinical outcomes of clopidogrel and ticagrelor uses in older patients with an acute coronary syndrome (ACS).

Methods

Older patients (aged ≥65 years) with ACS who underwent percutaneous coronary intervention (PCI) were divided into clopidogrel-treated and ticagrelor-treated groups. The primary observational endpoint was the occurrence of net adverse clinical and cerebral events (NACCEs) during a 12-month period, which is defined as the composite endpoint of all-cause death, myocardial infarction (MI), stroke, stent thrombosis, urgent coronary revascularization, and clinically significant bleeding. The secondary endpoints were clinically significant bleeding and major adverse clinical and cerebral events (MACCEs).

Results

This study included a total of 2,611 patients. Of them, 1,636 received clopidogrel and 975 received ticagrelor. Between patients receiving clopidogrel and those receiving ticagrelor, no significant differences were noted in NACCE (8.4 vs. 9.7%, respectively; adjusted hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.66–1.12) or MACCE (7.1 vs. 7.0%, respectively; adjusted HR, 1.13; 95% CI, 0.83–1.55) during the 12-month follow-up period. In contrast, the occurrence of clinically significant bleeding was significantly less in clopidogrel-treated patients compared with that in ticagrelor-treated patients (27, 1.7%, vs. 31, 3.2%, respectively; adjusted HR, 0.42; 95% CI, 0.25–0.69). Stratified analyses revealed no significant association between age (≥75 years vs. <75 years) and treatment condition in terms of primary or secondary endpoints.

Conclusion

This study showed that clopidogrel and ticagrelor had comparable net clinical benefits in patients with ACS aged ≥65 years. Additionally, clopidogrel was associated with a significantly lower risk of major bleeding than ticagrelor without an increase in ischemic risk. These findings suggest that clopidogrel is an effective alternative to the more potent P2Y12 inhibitor ticagrelor in older patients.
Prenatal Progestin Exposure-Mediated Oxytocin Suppression Contributes to Social Deficits in Mouse Offspring
Authors: Huang Saijun , Zeng Jiaying , Sun Ruoyu , Yu Hong , Zhang Haimou , Su Xi , Yao Paul
Published: March 2022

Epidemiological studies have shown that maternal hormone exposure is associated with autism spectrum disorders (ASD). The hormone oxytocin (OXT) is a central nervous neuropeptide that plays an important role in social behaviors as well as ASD etiology, although the detailed mechanism remains largely unknown. In this study, we aim to investigate the potential role and contribution of OXT to prenatal progestin exposure-mediated mouse offspring. Our in vitro study in the hypothalamic neurons that isolated from paraventricular nuclei area of mice showed that transient progestin exposure causes persistent epigenetic changes on the OXT promoter, resulting in dissociation of estrogen receptor β (ERβ) and retinoic acid-related orphan receptor α (RORA) from the OXT promoter with subsequent persistent OXT suppression. Our in vivo study showed that prenatal exposure of medroxyprogesterone acetate (MPA) triggers social deficits in mouse offspring; prenatal OXT deficiency in OXT knockdown mouse partly mimics, while postnatal ERβ expression or postnatal OXT peptide injection partly ameliorates, prenatal MPA exposure-mediated social deficits, which include impaired social interaction and social abilities. On the other hand, OXT had no effect on prenatal MPA exposure-mediated anxiety-like behaviors. We conclude that prenatal MPA exposure-mediated oxytocin suppression contributes to social deficits in mouse offspring.
Effectiveness of Remotely Delivered Interventions to Simultaneously Optimize Management of Hypertension, Hyperglycemia and Dyslipidemia in People With Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Fernando Malindu E. , Seng Leonard , Drovandi Aaron , Crowley Benjamin J. , Golledge Jonathan
Published: March 2022

Background

Remotely delivered interventions may be more efficient in controlling multiple risk factors in people with diabetes.

Purpose

To pool evidence from randomized controlled trials testing remote management interventions to simultaneously control blood pressure, blood glucose and lipids.

Data Sources

PubMed/Medline, EMBASE, CINAHL and the Cochrane library were systematically searched for randomized controlled trials (RCTs) until 20th June 2021.

Study Selection

Included RCTs were those that reported participant data on blood pressure, blood glucose, and lipid outcomes in response to a remotely delivered intervention.

Data Extraction

Three authors extracted data using a predefined template. Primary outcomes were glycated hemoglobin (HbA1c), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), systolic and diastolic blood pressure (SBP & DBP). Risk of bias was assessed using the Cochrane collaboration RoB-2 tool. Meta-analyses are reported as standardized mean difference (SMD) with 95% confidence intervals (95%CI).

Data Synthesis

Twenty-seven RCTs reporting on 9100 participants (4581 intervention and 4519 usual care) were included. Components of the remote management interventions tested were identified as patient education, risk factor monitoring, coaching on monitoring, consultations, and pharmacological management. Comparator groups were typically face-to-face usual patient care. Remote management significantly reduced HbA1c (SMD -0.25, 95%CI -0.33 to -0.17, p<0.001), TC (SMD -0.17, 95%CI -0.29 to -0.04, p<0.0001), LDL-c (SMD -0.11, 95%CI -0.19 to -0.03, p=0.006), SBP (SMD -0.11, 95%CI -0.18 to -0.04, p=0.001) and DBP (SMD -0.09, 95%CI -0.16 to -0.02, p=0.02), with low to moderate heterogeneity (I²= 0 to 75). Twelve trials had high risk of bias, 12 had some risk and three were at low risk of bias.

Limitations

Heterogeneity and potential publication bias may limit applicability of findings.

Conclusions

Remote management significantly improves control of modifiable risk factors.

Systematic Review Registration

[https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=258433], identifier PROSPERO (CRD42021258433).
Connecting the Dots Between the Gut–IGF-1–Prostate Axis: A Role of IGF-1 in Prostate Carcinogenesis
Authors: Matsushita Makoto , Fujita Kazutoshi , Hatano Koji , De Velasco Marco A. , Uemura Hirotsugu , Nonomura Norio
Published: March 2022

Prostate cancer (PCa) is the most common malignancy in men worldwide, thus developing effective prevention strategies remain a critical challenge. Insulin-like growth factor 1 (IGF-1) is produced mainly in the liver by growth hormone signaling and is necessary for normal physical growth. However, several studies have shown an association between increased levels of circulating IGF-1 and the risk of developing solid malignancies, including PCa. Because the IGF-1 receptor is overexpressed in PCa, IGF-1 can accelerate PCa growth by activating phosphoinositide 3-kinase and mitogen-activated protein kinase, or increasing sex hormone sensitivity. Short-chain fatty acids (SCFAs) are beneficial gut microbial metabolites, mainly because of their anti-inflammatory effects. However, we have demonstrated that gut microbiota-derived SCFAs increase the production of IGF-1 in the liver and prostate. This promotes the progression of PCa by the activation of IGF-1 receptor downstream signaling. In addition, the relative abundance of SCFA-producing bacteria, such as Alistipes, are increased in gut microbiomes of patients with high-grade PCa. IGF-1 production is therefore affected by the gut microbiome, dietary habits, and genetic background, and may play a central role in prostate carcinogenesis. The pro-tumor effects of bacteria and diet-derived metabolites might be potentially countered through dietary regimens and supplements. The specific diets or supplements that are effective are unclear. Further research into the “Gut–IGF-1–Prostate Axis” may help discover optimal diets and nutritional supplements that could be implemented for prevention of PCa.
Evaluation Model and Application of Shale Oil Production Efficiency Under Energy-Depleted Development Mode in Jimsar Sag
Authors: Gao Yang , Zhi Dongming , Li Yingyan , Jiang Zhenxue , Deng Yuan , Qin Jianhua
Published: March 2022

In order to reveal the shale oil production mechanism and production efficiency under the energy-depleted development mode, experiments on expulsion oil based on imbibition and elastic energy release under high temperature and pressure were carried out, and nuclear magnetic resonance on-line monitoring was used to observe the production characteristics of shale oil. The experimental results show that the imbibition-expulsion oil mainly occurs in the small-size pore-throat system. Under the condition of high temperature and pressure, the oil-expulsion efficiency is generally less than 2% affected by pore pressure, which is significantly different from the conventional imbibition experiment results. Although elastic-energy expulsion oil occurs in different sizes of pore-throat systems, the oil-expulsion efficiency in large size pore-throat systems is more sensitive to temperature. Overall, the total elastic-energy oil-expulsion efficiency is significantly positively correlated with reservoir physical properties, production differential pressure and temperature, and negatively correlated with crude oil viscosity. Comprehensively considering various geological factors affecting oil-expulsion efficiency, the shale oil production efficiency evaluation model under the energy-depleted development mode is constructed, and the movable oil porosity of shale oil development section in the study area is evaluated. The results show that there is a good positive correlation between movable oil porosity and oil production intensity. The movable oil porosity of dry layer is generally lower than 0.5% and that of poor oil layer is between 0.5% and 1.5%. When the movable oil porosity is between 1.5 and 2.5%, it can be determined as the type II oil layer, and for more than 2.5%, it is the type I oil layer. The single-well evaluation results show that the shale oil “sweet spots” of the Lucaogou Formation in Jimsar Sag are mainly distributed in P2l22−1∼ P2l22−3 and P2l12−1∼ P2l12−3, which is in good agreement with the current development status.
Experimental Analysis and Performance Evaluation of Spider Hydraulic Buffer for Rod Dropping in Reactor
Authors: Yue Ti , Yuan Pan , Huang Shan , Zhu Fawen , Li Yuanming , Huang Chunlan , Zheng Lele , Wang Haoyu , Liu Menglong
Published: March 2022

Control rod drop is one of the key measures for the safe shutdown of the reactor. The two important evaluation indicators of the drop process are the drop time-length and the maximum impact force. By theoretical and experimental methods, this paper analyzes the influencing factors and evaluates the performance of a new type of spider hydraulic buffer with compact structure and ingenious design, which couples mechanical force and fluid resistance. First, through experiments, it is found that the real-time curve of the maximum impact force often has a bimodal structure. And the double peaks vary with the change of the internal structure of the hydraulic buffer. Secondly, since there are many variables about the structure (aperture, position, quantity, piston stroke et al.), in order to consider their influence on the maximum impact force, an equivalent ongoing flow area of the drain holes is introduced. It suggested that when the flow area of the working holes which can be covered by the stroke is close to the flow area of the remaining holes, the impact force tends to appear a minimum value. A relationship between the maximum impact force and the structure is proposed accordingly. Finally, this paper proposes a quantitative evaluation method for comprehensive buffering performance, in which the comprehensive performance evaluation factor η (0<η < 1) takes into account both the maximum impact force and the drop time. The smaller the maximum impact force and the rod drop time-length, the closer the evaluation factor η is to 1, indicating that the buffering performance is better. The research in this paper will not only help to further understand the mechanism of the drop rod buffering process, but also contribute to the structural optimization of the subsequent spider hydraulic buffer.
Pollutant Flux Estimation of the Lijiang River Based on an Improved Prediction-Correction Method
Authors: Chen Junhong , Shi Wenfei , Jin Xin
Published: March 2022

Pollutant flux estimation and the analysis of flux variations are the basis for water quality assessment and water pollution control. At present, pollution flux estimation has certain shortcomings, such as a low frequency of water quality monitoring and inadequate calculation methods. To improve the rationality and reliability of river pollution flux estimation results, an improved prediction-correction pollution flux estimation method was developed by combining the LOADEST model and the Kalman filtering algorithm. By establishing the regression equation between pollutant flux and daily discharge, the predicted pollution flux procedure can be calculated using the LOADEST model. In a subsequent step, the pollutant flux is corrected based on the Kalman filtering algorithm. The improved method was applied to estimate the fluxes of chemical oxygen demand (COD), ammonia nitrogen (NH3-N), and total phosphorus (TP) at the Guilin Section of the Lijiang River from 2010 to 2019. The estimated fluxes were in good agreement with the measured ones, with relative deviation values for COD, NH3-N, and TP of 2.27, 3.20, and 1.39%, respectively. The improved method can reasonably estimate fluctuations in river pollution fluxes without requiring more data. The results in the present study provide powerful scientific basis for pollutant flux estimation under low-frequency water quality monitoring.
Increasing Anthropogenic Disturbance Restricts Wildebeest Movement Across East African Grazing Systems
Authors: Stabach Jared A. , Hughey Lacey F. , Crego Ramiro D. , Fleming Christen H. , Hopcraft J. Grant C. , Leimgruber Peter , Morrison Thomas A. , Ogutu Joseph O. , Reid Robin S. , Worden Jeffrey S. , Boone Randall B.
Published: March 2022

The ability to move is essential for animals to find mates, escape predation, and meet energy and water demands. This is especially important across grazing systems where vegetation productivity can vary drastically between seasons or years. With grasslands undergoing significant changes due to climate change and anthropogenic development, there is an urgent need to determine the relative impacts of these pressures on the movement capacity of native herbivores. To measure these impacts, we fitted 36 white-bearded wildebeest (Connochaetes taurinus) with GPS collars across three study areas in southern Kenya (Amboseli Basin, Athi-Kaputiei Plains, and Mara) to test the relationship between movement (e.g., directional persistence, speed, home range crossing time) and gradients of vegetation productivity (i.e., NDVI) and anthropogenic disturbance. As expected, wildebeest moved the most (21.0 km day–1; CI: 18.7–23.3) across areas where movement was facilitated by low human footprint and necessitated by low vegetation productivity (Amboseli Basin). However, in areas with moderate vegetation productivity (Athi-Kaputiei Plains), wildebeest moved the least (13.3 km day–1; CI: 11.0–15.5). This deviation from expectations was largely explained by impediments to movement associated with a large human footprint. Notably, the movements of wildebeest in this area were also less directed than the other study populations, suggesting that anthropogenic disturbance (i.e., roads, fences, and the expansion of settlements) impacts the ability of wildebeest to move and access available resources. In areas with high vegetation productivity and moderate human footprint (Mara), we observed intermediate levels of daily movement (14.2 km day–1; CI: 12.3–16.1). Wildebeest across each of the study systems used grassland habitats outside of protected areas extensively, highlighting the importance of unprotected landscapes for conserving mobile species. These results provide unique insights into the interactive effects of climate and anthropogenic development on the movements of a dominant herbivore in East Africa and present a cautionary tale for the development of grazing ecosystems elsewhere.
Beyond Genes: Inclusion of Alternative Splicing and Alternative Polyadenylation to Assess the Genetic Architecture of Predisposition to Voluntary Alcohol Consumption in Brain of the HXB/BXH Recombinant Inbred Rat Panel
Authors: Lusk Ryan , Hoffman Paula L. , Mahaffey Spencer , Rosean Samuel , Smith Harry , Silhavy Jan , Pravenec Michal , Tabakoff Boris , Saba Laura M.
Published: March 2022

Post transcriptional modifications of RNA are powerful mechanisms by which eukaryotes expand their genetic diversity. For instance, researchers estimate that most transcripts in humans undergo alternative splicing and alternative polyadenylation. These splicing events produce distinct RNA molecules, which in turn yield distinct protein isoforms and/or influence RNA stability, translation, nuclear export, and RNA/protein cellular localization. Due to their pervasiveness and impact, we hypothesized that alternative splicing and alternative polyadenylation in brain can contribute to a predisposition for voluntary alcohol consumption. Using the HXB/BXH recombinant inbred rat panel (a subset of the Hybrid Rat Diversity Panel), we generated over one terabyte of brain RNA sequencing data (total RNA) and identified novel splice variants (via StringTie) and alternative polyadenylation sites (via aptardi) to determine the transcriptional landscape in the brains of these animals. After establishing an analysis pipeline to ascertain high quality transcripts, we quantitated transcripts and integrated genotype data to identify candidate transcript coexpression networks and individual candidate transcripts associated with predisposition to voluntary alcohol consumption in the two-bottle choice paradigm. For genes that were previously associated with this trait (e.g., Lrap, Ift81, and P2rx4) (Saba et al., Febs. J., 282, 3556–3578, Saba et al., Genes. Brain. Behav., 20, e12698), we were able to distinguish between transcript variants to provide further information about the specific isoforms related to the trait. We also identified additional candidate transcripts associated with the trait of voluntary alcohol consumption (i.e., isoforms of Mapkapk5, Aldh1a7, and Map3k7). Consistent with our previous work, our results indicate that transcripts and networks related to inflammation and the immune system in brain can be linked to voluntary alcohol consumption. Overall, we have established a pipeline for including the quantitation of alternative splicing and alternative polyadenylation variants in the transcriptome in the analysis of the relationship between the transcriptome and complex traits.
Genomic Imprinting in the New Omics Era: A Model for Systems-Level Approaches
Authors: Hubert Jean-Noël , Demars Julie
Published: March 2022

Genomic imprinting represents a noteworthy inheritance mechanism leading to allele-specific regulations dependent of the parental origin. Imprinted loci are especially involved in essential mammalian functions related to growth, development and behavior. In this mini-review, we first offer a summary of current representations associated with genomic imprinting through key results of the three last decades. We then outline new perspectives allowed by the spread of new omics technologies tackling various interacting levels of imprinting regulations, including genomics, transcriptomics and epigenomics. We finally discuss the expected contribution of new omics data to unresolved big questions in the field.
The Transcription of ZIP9 Is Associated With the Macrophage Polarization and the Pathogenesis of Hepatocellular Carcinoma
Authors: Gou Yingying , Yang Dan , Tian Taikun , Zhu Xingguo , Zhang Raorao , Ren Jiaqi , Tu Dezhen , Luo Yi , Miao Yuqing , Zhao Huan , Wang Yu , Wei Bin
Published: March 2022

Hepatocellular carcinoma (HCC) is one of the most common digestive system cancers (DSCs) with a poor prognosis. Zinc‐regulated transporter (ZRT)/iron‐regulated transporter (IRT) like protein transporters (ZIPs) encode membrane transport proteins, which are responsible for the absorption of zinc and play important roles in the pathogenesis of various human cancers. Tumor-associated macrophages (TAMs) are important participants in the regulation of tumor microenvironment and the development of HCC. Individual role of each ZIP involved in hepatocarcinogenesis remains elusive. In this study, the transcription patterns of ZIPs in the DSCs were screened firstly through GEPIA2 database. Interestingly, the analysis of the DSCs data showed the distinct mRNA levels of ZIPs between DSCs tissues and healthy controls. Notably, the transcription levels of ZIP2, ZIP5, ZIP8, ZIP9 and ZIP14 were decreased significantly in the tissues of human liver cancer compared to paracarcinoma liver tissues. To further confirm the mRNA transcriptional changes of Zips in HCC, N-Nitrosodiethylamine (DEN) combined with carbon tetrachloride (CCl4) inducing mouse model of HCC were established. Consistently, the mRNA levels of Zip2, Zip9, and Zip14 in liver tissues of HCC induced mice were also decreased compared with the healthy controls. In addition, mouse peritoneal elucidated macrophages (PEMs)-derived M1/M2 macrophages in vitro, as well as human patients of HCC-derived TAMs, were used to examine the transcription levels of ZIPs. Our results showed that both Zip2 and Zip9 were up-regulated in M2-polarized macrophages. Zip2 transcript was also up-regulated M1-polarized macrophages, but Zip9 was slightly down-regulated. TAMs generated from human liver cancer tissues also displayed a decrease in ZIP9 transcription compared to paracarcinoma tissues. To further explore the role of Zip9 in M1/M2 polarization, the siRNA knockdown results revealed that Zip9, but not Zip2, could promote M2 macrophage polarization and impair M1 macrophage polarization. Mechanistically, Zip9 enhances phosphorylated STAT6 to promote M2 macrophage polarization but suppresses the phosphorylation of IκBα/β to inhibit M1 macrophage polarization. Together, our results indicate that ZIP9 may involve in macrophages polarity in HCC development and may be a potent new biomarker for the diagnosis of HCC.
Anti-FcαRI Monoclonal Antibodies Resolve IgA Autoantibody-Mediated Disease
Authors: Bos Amelie , Aleyd Esil , van der Steen Lydia P. E. , Winter P. J. , Heemskerk Niels , Pouw Stephan M. , Boon Louis , Musters Rene J. P. , Bakema Jantine E. , Sitaru Cassian , Cogné Michel , van Egmond Marjolein
Published: March 2022

Immunoglobulin A (IgA) is generally considered as a non-inflammatory regulator of mucosal immunity, and its importance in diversifying the gut microbiota is increasingly appreciated. IgA autoantibodies have been found in several autoimmune or chronic inflammatory diseases, but their role in pathophysiology is ill-understood. IgA can interact with the Fc receptor FcαRI on immune cells. We now established a novel IgA autoimmune blistering model, which closely resembles the human disease linear IgA bullous disease (LABD) by using genetically modified mice that produce human IgA and express human FcαRI. Intravital microscopy demonstrated that presence of IgA anti-collagen XVII, - the auto-antigen in LABD-, resulted in neutrophil activation and extravasation from blood vessels into skin tissue. Continued exposure to anti-collagen XVII IgA led to massive neutrophil accumulation, severe tissue damage and blister formation. Importantly, treatment with anti-FcαRI monoclonal antibodies not only prevented disease, but was also able to resolve existing inflammation and tissue damage. Collectively, our data reveal a novel role of neutrophil FcαRI in IgA autoantibody-mediated disease and identify FcαRI as promising new therapeutic target to resolve chronic inflammation and tissue damage.
Pyolysin of Trueperella pyogenes Induces Pyroptosis and IL-1β Release in Murine Macrophages Through Potassium/NLRP3/Caspase-1/Gasdermin D Pathway
Authors: Liang Hongmin , Wang Bing , Wang Junwei , Ma Bo , Zhang Wenlong
Published: March 2022

Trueperella pyogenes (T. pyogenes) is a commensal and an opportunistic pathogen of animals. This organism can cause inflammatory diseases, such as pneumonia, mastitis and endometritis in hosts. However, the molecular basis for the pro-inflammatory properties of this organism is still largely unknown. In the current study, using murine macrophages as model, the ability of T. pyogenes to induce pyroptosis was first determined. Then, pyolysin (PLO), a cholesterol-dependent cytolysin secreted by T. pyogenes, was found to be closely related to T. pyogenes-induced pyroptosis. Next, our work showed that PLO can form pores in the cell membrane, leading to the efflux of potassium (K+), NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-mediated caspase-1 activation, and gasdermin D (GSDMD) cleavage. Inhibition of the K+/NLRP3/caspase-1/GSDMD pathway abolished T. pyogenes and PLO-induced IL-1β release. Taken together, these results indicate T. pyogenes-induced inflammation is related to PLO-induced pyroptosis and IL-1β release. Our work shed light on the pathogenesis of T. pyogenes and the interaction between T. pyogenes and hosts’ immune system.
Genetic Variants of the BAFF Gene and Risk of Fatigue Among Patients With Primary Sjögren’s Syndrome
Authors: Flessa Christina-Maria , Zampeli Evangelia , Evangelopoulos Maria-Eleftheria , Natsis Vasilis , Bodewes Iris L. A. , Huijser Erika , Versnel Marjan A. , Moutsopoulos Haralampos M. , Mavragani Clio P.
Published: March 2022

Background/Purpose

Primary Sjögren’s Syndrome (SS) is characterized by B lymphocyte hyperactivity with B cell activating factor (BAFF) acting as an important regulator. Single Nucleotide Polymorphisms (SNPs) of the BAFF gene have been implicated in the pathogenesis of several autoimmune diseases characterized by heightened fatigue levels, including primary SS. We aimed to explore potential associations between BAFF SNPs and fatigue status of primary SS patients.

Methods

Fatigue status was assessed in 199 consecutive primary SS patients (Greek cohort) using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale. Clinical, histological, laboratory, psychometric and personality data were also collected. DNA extracted from peripheral blood of all patients underwent evaluation for the presence of five BAFF SNPs (rs9514827, rs1041569, rs9514828, rs1224141, rs12583006) by PCR. To confirm our findings, an independent replicative cohort of 62 primary SS patients (Dutch cohort) was implemented. Finally, 52 multiple sclerosis (MS) patients were served as disease controls (MS cohort). Analysis of BAFF SNPs in association with fatigue levels was performed by the online platforms SNPStats and SHEsis and the SPSS 26 and Graph Pad Prism 8.00 software.

Results

TT genotype of the rs9514828 BAFF polymorphism was significantly less frequent in the fatigued primary SS patients of the Greek cohort compared to the non-fatigued (14.1% vs 33.3%). The corresponding ORs [95%CI] in the dominant and overdominant models were 0.33 [0.15-0.72], p=0.003 and 0.42 [0.23-0.78], p=0.005 respectively. The association remained significant after adjustment for the variables contributing to fatigue in the univariate analysis (OR [95% CI]: 0.3 [0.1-0.9], p=0.026). Accordingly, in the Dutch cohort, there was a trend of lower mental fatigue among patients carrying the TT rs9514828 BAFF genotype compared to their CC counterparts (4.1 ± 2.4 vs 6.0 ± 2.2 respectively, p=0.06). The rs9514828 BAFF SNP was not significantly associated with fatigue in the MS cohort.

Conclusions

We report a novel association between genetic makeup and primary SS-associated fatigue with the rs9514828 TT genotype decreasing the likelihood of fatigue development among these patients. These findings need validation in multi-center studies.