bluuebunny/crossref_metadata_2025 huggingface dataset:
A Biomimetic Platelet-Rich Plasma-Based Interpenetrating Network Printable Hydrogel for Bone Regeneration
Authors: Tang Shijia , Wang Lin , Zhang Yunyang , Zhang Feimin
Published: April 2022

Repair of bone defects caused by trauma or diseases is the primary focus of prosthodontics. Hydrogels are among the most promising candidates for bone tissue regeneration due to their unique features such as excellent biocompatibility, similarities to biological tissues, and plasticity. Herein, we developed a type of novel biomimetic interpenetrating polymeric network (IPN) hydrogel by combining methacrylated alginate and 4-arm poly (ethylene glycol)-acrylate (4A-PEGAcr) through photo-crosslinking. Platelet-rich plasma (PRP), a patient-specific source of autologous growth factors, was incorporated into the hydrogel, and thereafter the hydrogels were biological mineralized by simulated body fluid (SBF). Physical properties of hydrogels were comprehensively characterized. In vitro studies demonstrated that the incorporation of PRP and biomineralization promoted the biocompatibility of hydrogel. Strikingly, the osteogenic bioactivities, including ALP activity, mineralized nodule formation, and expression of osteogenic markers were found substantially enhanced by this biomineralized PRP-hydrogel. Finally, a rabbit model of bone defect was employed to assess in vivo bone regeneration, micro-CT analysis showed that the biomineralized PRP-hydrogels could significantly accelerate bone generation. We believed that this novel biomineralized PRP-incorporated IPN hydrogel could be promising scaffolds for bone tissue regeneration.
Clinical Significance of the Expression of Co-Stimulatory Molecule B7-H3 in Papillary Thyroid Carcinoma
Authors: Zhao Bohui , Huang Zehao , Zhu Xinyi , Cai Huizhu , Huang Yingcheng , Zhang Xiwei , Zhang Zongmin , Lu Haizhen , An Changming , Niu Lijuan , Li Zhengjiang
Published: April 2022

Background: B7-H3, also known as CD276, an important immune checkpoint member of the B7-CD28 family, is confirmed as a promising target after PD-L1 in clinical trials. Although the overexpression of B7-H3 has been associated with invasive metastatic potential and poor prognosis in multiple types of cancer, nothing is known regarding the expression profiles of B7-H3 in papillary thyroid carcinoma (PTC). In this study, we carried out a large-scale analysis of B7-H3 expression in PTC patients and evaluated the potential clinical significance of B7-H3.

Methods: In total, data from 1,210 samples, including 867 cases from TCGA and four GEO datasets, were collected for B7-H3–related transcriptome analyses, and 343 postoperative, whole-tumor sections were collected from patients with PTC at our institute for B7-H3–specific immunohistochemistry (IHC) staining. The statistical analysis was primarily accomplished using the R project for statistical computing.

Results: B7-H3 positivity was found in 84.8% of PTC patients (291/343), and the mRNA and protein expression levels of B7-H3 in PTC were markedly higher than those of para-tumor tissues (p < 0.001), demonstrating that B7-H3 can serve as a potential diagnostic biomarker for PTC. The significant upregulation of B7-H3 in PTC is caused by distinct patterns of CNVs and CpG DNA methylation. Functional enrichment analysis confirmed that high B7-H3 expression was significantly associated with specific immune features and angiogenesis. High B7-H3 protein expression was associated with tumor size (p = 0.022), extrathyroidal extension (ETE) (p = 0.003), and lymph node metastasis (LNM) (p < 0.001). More importantly, multivariate analysis confirmed that B7-H3 was an independent predictor of relapse-free survival (RFS) (p < 0.05). In the subgroup analysis, positive B7-H3 staining was associated with worse RFS in patients with primary tumor size ≥2 cm (p < 0.05), age ≥55 years (p < 0.05), LNM (p = 0.07), multifocality (p < 0.05), and ETE (p < 0.05). In addition, Circos plots indicated that B7-H3 was significantly associated with other immune checkpoints in the B7-CD28 family.

Conclusion: This is the first comprehensive study to elucidate the expression profile of B7-H3 in PTC. Our observations revealed that B7-H3 is a novel independent biomarker for predicting LNM and disease recurrence for PTC patients, and it thus may serve as an indicator that could be used to improve risk-adapted therapeutic strategies and a novel target for immunotherapy strategies for patients who undergo an aggressive disease course.
Plasmalogenic Lipid Analogs as Platelet-Activating Factor Antagonists: A Potential Novel Class of Anti-inflammatory Compounds
Authors: Rong Pu , Wang Jie-Li , Angelova Angelina , Almsherqi Zakaria A. , Deng Yuru
Published: April 2022

Plasmalogens and Platelet-Activating Factor (PAF) are both bioactive ether phospholipids. Whereas plasmalogens are recognized for their important antioxidant function and modulatory role in cell membrane structure and dynamics, PAF is a potent pro-inflammatory lipid mediator known to have messenger functions in cell signaling and inflammatory response. The relationship between these two types of lipids has been rarely studied in terms of their metabolic interconversion and reciprocal modulation of the pro-inflammation/anti-inflammation balance. The vinyl-ether bonded plasmalogen lipid can be the lipid sources for the precursor of the biosynthesis of ether-bonded PAF. In this opinion paper, we suggest a potential role of plasmalogenic analogs of PAF as modulators and PAF antagonists (anti-PAF). We discuss that the metabolic interconversion of these two lipid kinds may be explored towards the development of efficient preventive and relief strategies against PAF-mediated pro-inflammation. We propose that plasmalogen analogs, acting as anti-PAF, may be considered as a new class of bioactive anti-inflammatory drugs. Despite of the scarcity of available experimental data, the competition between PAF and its natural plasmalogenic analogs for binding to the PAF receptor (PAF-R) can be proposed as a mechanistic model and potential therapeutic perspective against multiple inflammatory diseases (e.g., cardiovascular and neurodegenerative disorders, diabetes, cancers, and various manifestations in coronavirus infections such as COVID-19).
A Current Overview of the Biological Effects of Combined Space Environmental Factors in Mammals
Authors: Xu Ying , Pei Weiwei , Hu Wentao
Published: April 2022

Distinct from Earth’s environment, space environmental factors mainly include space radiation, microgravity, hypomagnetic field, and disrupted light/dark cycles that cause physiological changes in astronauts. Numerous studies have demonstrated that space environmental factors can lead to muscle atrophy, bone loss, carcinogenesis, immune disorders, vascular function and cognitive impairment. Most current ground-based studies focused on single environmental factor biological effects. To promote manned space exploration, a better understanding of the biological effects of the spaceflight environment is necessary. This paper summarizes the latest research progress of the combined biological effects of double or multiple space environmental factors on mammalian cells, and discusses their possible molecular mechanisms, with the hope of providing a scientific theoretical basis to develop appropriate countermeasures for astronauts.
ULK4 in Neurodevelopmental and Neuropsychiatric Disorders
Authors: Luo Shilin , Zheng Nanxi , Lang Bing
Published: April 2022

The gene Unc51-like kinase 4 (ULK4) belongs to the Unc-51-like serine/threonine kinase family and is assumed to encode a pseudokinase with unclear function. Recently, emerging evidence has suggested that ULK4 may be etiologically involved in a spectrum of neuropsychiatric disorders including schizophrenia, but the underlying mechanism remains unaddressed. Here, we summarize the key findings of the structure and function of the ULK4 protein to provide comprehensive insights to better understand ULK4-related neurodevelopmental and neuropsychiatric disorders and to aid in the development of a ULK4-based therapeutic strategy.
Optimization of Automatic Synthesis and Separation of [18F] AV-45 and Quality Control
Authors: Zhang Qi-Zhou , Li Yu-Bin , Yilihamu Nazi , Li Xiao-Hong , Ba Ya , Qin Yong-De
Published: April 2022

Objective: Based on the Tracerlab FXF-N platform, a synthesis program and preparative high-performance liquid chromatography (HPLC) purification program edited by us can stably and repeatedly produce [18F] AV-45 without changing the process. The [18F] AV-45 produced meets the main indexes of radiopharmaceutical intravenous preparations.

Methods: The O-toluene sulfonated precursor (1 mg) was subjected to nucleophilic radiofluorination at 115°C in anhydrous dimethyl sulfoxide (DMSO), then the protective group was hydrolyzed by acid. The neutralized reaction mixture was purified through a preparative HPLC then formulated for injection using a C18 purification cartridge. This method yielded a relatively pure [18F] AV-45 product with high specific activity.

Results: Four consecutive radiochemical synthesis operations were carried out in this experiment; the average production time of [18F] AV-45 preparation was 60 min, the radiochemical yield was 14.8 ± 2.1% (n = 4), the radiochemical purity was greater than 95%, and the other important quality control indexes met the requirements of radioactive drugs for intravenous administration.

Conclusion: This experiment was based on the Tracerlab FXF-N platform with the synthesis program and preparative HPLC purification program edited by us. Through screening and optimization of the separation and purification system and the separation and analysis system, as well as automatic radiochemical synthesis and preparation quality control, intravenous [18F] AV-45 was successfully prepared.
Characteristics of COVID-19 Patients With SARS-CoV-2 Positivity in Feces
Authors: Wu Wenrui , Shi Ding , Zhu Xueling , Xie Jiaojiao , Xu Xinyi , Chen Yanfei , Wu Jingjing , Li Lanjuan
Published: April 2022

Background

SARS-CoV-2 is highly contagious and poses a great threat to epidemic control and prevention. The possibility of fecal-oral transmission has attracted increasing concern. However, viral shedding in feces has not been completely investigated.

Methods

This study retrospectively reviewed 97 confirmed coronavirus disease 2019 (COVID-19) patients hospitalized at the First Affiliated Hospital, School of Medicine, Zhejiang University, from January 19 to February 17, 2020. SARS-CoV-2 RNA in samples of sputum, nasopharyngeal or throat swabs, bronchoalveolar lavage and feces was detected by real-time reverse transcription polymerase chain reaction (RT–PCR). Clinical characteristics and parameters were compared between groups to determine whether fecal RNA was positive.

Results

Thirty-four (35.1%) of the patients showed detectable SARS-CoV-2 RNA in feces, and 63 (64.9%) had negative detection results. The median time of viral shedding in feces was approximately 25 days, with the maximum time reaching 33 days. Prolonged fecal-shedding patients showed longer hospital stays. Those patients for whom fecal viral positivity persisted longer than 3 weeks also had lower plasma B-cell counts than those patients in the non-prolonged group [70.5 (47.3-121.5) per μL vs. 186.5 (129.3-376.0) per μL, P = 0.023]. Correlation analysis found that the duration of fecal shedding was positively related to the duration of respiratory viral shedding (R = 0.70, P < 0.001) and negatively related to peripheral B-cell counts (R = -0.44, P < 0.05).

Conclusions

COVID-19 patients who shed SARS-CoV-2 RNA in feces presented similar clinical characteristics and outcomes as those who did not shed SARS-CoV-2 RNA in feces. The prolonged presence of SARS-CoV-2 nucleic acids in feces was highly correlated with the prolonged shedding of SARS-CoV-2 RNA in the respiratory tract and with lower plasma B-cell counts.
Sex Difference Trend in 5-Year Mortality Among Patients With Coronary Artery Disease: A 24,432 Chinese Cohort Study From 2007 to 2014
Authors: Huang Haozhang , Lai Wenguang , Li Qiang , Wei Haiyan , Remutula Nuerbahaer , Tuersun Tilakezi , Yang Zhou , Bao Kunming , Yan Zelin , Wang Bo , He Yibo , Chen Shiqun , Ou Chun-Quan , Yang Heyin , Chen Jiyan , Liu Jin , Liu Yong
Published: April 2022

Background

The sex difference trend of short-term mortality in coronary artery disease (CAD) is narrowing, which has been reported in the previous studies. However, no studies assess the sex difference temporal trends of CAD mortality in China especially long-term mortality trend.

Methods

Based on the registry at Guangdong Provincial People's Hospital which is the largest cardiovascular center in South China, this retrospective cohort study included 24,432 hospitalized patients with CAD confirmed by coronary angiography from January 2007 to December 2014. Women and men were followed for 1-year and 5-year all-cause mortality.

Results

From 2007 to 2014, 5-year age-standardized mortality increased from 10.0 to 11.7% in men (p for trend < 0.001) and from 11.5 to 8.1% in women (p for trend = 0.99). The multivariable-adjusted hazard ratios (95% CI), which compare women with men, were from 1.02 (0.39–2.67) to 0.66 (0.39–1.12) for 1-year all-cause mortality and 1.23 (0.64–2.36) to 0.59 (0.44–0.79) for 5-year all-cause mortality (p for trend = 0.04).

Conclusion

Our study found that the mortality risk among men and women was similar in the 1-year prognosis of CAD, and there was no significant downward trend. In the 5-year long-term prognosis of CAD, the mortality risk among men continued to rise, while women had reached the peak, which means that the mortality risk continues to be higher among men than women.
Left Ventricular Remodeling in Non-syndromic Mitral Valve Prolapse: Volume Overload or Concomitant Cardiomyopathy?
Authors: Pype Lobke L. , Bertrand Philippe B. , Paelinck Bernard P. , Heidbuchel Hein , Van Craenenbroeck Emeline M. , Van De Heyning Caroline M.
Published: April 2022

Mitral valve prolapse (MVP) is a common valvular disorder that can be associated with mitral regurgitation (MR), heart failure, ventricular arrhythmias and sudden cardiac death. Given the prognostic impact of these conditions, it is important to evaluate not only mitral valve morphology and regurgitation, but also the presence of left ventricular (LV) function and remodeling. To date, several possible hypotheses have been proposed regarding the underlying mechanisms of LV remodeling in the context of non-syndromic MVP, but the exact pathophysiological explanation remains elusive. Overall, volume overload related to severe MR is considered the main cause of LV dilatation in MVP. However, significant LV remodeling has been observed in patients with MVP and no/mild MR, particularly in patients with bileaflet MVP or Barlow’s disease, generating several new hypotheses. Recently, the concept of “prolapse volume” was introduced, adding a significant volume load to the LV on top of the transvalvular MR volume. Another possible hypothesis is the existence of a concomitant cardiomyopathy, supported by the link between MVP and myocardial fibrosis. The origin of this cardiomyopathy could be either genetic, a second hit (e.g., on top of genetic predisposition) and/or frequent ventricular ectopic beats. This review provides an overview of the different mechanisms and remaining questions regarding LV remodeling in non-syndromic MVP. Since technical specifications of imaging modalities impact the evaluation of MR severity and LV remodeling, and therefore might influence clinical decision making in these patients, this review will also discuss assessment of MVP using different imaging modalities.
Preventing Postpartum Venous Thromboembolism in 2022: A Narrative Review
Authors: Blondon Marc , Skeith Leslie
Published: April 2022

The postpartum period represents the most critical time for pregnancy-associated venous thromboembolism (VTE), which is responsible for substantial morbidity and an important cause of maternal mortality. The estimated risk of postpartum VTE of about 1/1,000 deliveries can be modulated with the knowledge of maternal and obstetrical risk factors, although a precise estimate remains challenging in individuals. The use of postpartum low-dose low-molecular-weight heparins are tailored at intermediate and high-risk groups to reduce the thrombotic burden, despite the lack of dedicated randomized controlled trials. In this review, we will highlight the contemporary evidence on the risk of postpartum VTE, its stratification and its prevention. We will also discuss our knowledge on the values and preferences of women for postpartum thromboprophylaxis and their adherence to treatment.
Distinct Mid-Latitude Eurasian Rossby Wave Trains Preceding Strong and Weak Cold Surges in Southern China
Authors: Lin Juanjuan , Cheung Ho-Nam
Published: April 2022

This study investigates the large-scale circulation anomalies of strong and weak cold surges in southern China. Results show that the strong and weak surges are associated with a distinct Rossby wave train across Eurasia projecting onto the Scandinavia (SCAND) and Eurasian (EU) patterns. On one hand, the strong surge is preceded by a positive SCAND pattern and a transition of the EU pattern from its negative to positive phase. The corresponding wave train propagates southeastward from East Asia to the North Pacific. This is associated with a strong intensification of the Siberian high, a deepened East Asian trough, and a sharp meridional pressure gradient between northern and southern China; these advect intense cold air masses from Siberia to southern China. On the other hand, the weak surge is preceded by a negative SCAND pattern and a positive EU pattern. The corresponding wave train does not propagate from East Asia to the North Pacific. This wave train has a weak impact on the East Asian winter monsoon circulation and corresponds to weak cold air advections towards southern China. Overall, the intra-seasonal variation of the Eurasian teleconnection patterns is crucial for a comprehensive understanding of the cold surge in southern China.
Fracture Effectiveness Evaluation of Ultra-Deep Tight Sandstone Reservoirs: A Case Study of the Keshen Gas Field, Tarim Basin, West China
Authors: Wang Zhimin , Xu Ke , Zhang Hui , Wang Haiying , Yin Guoqing , Wang Zhaohui , Zhao Wei
Published: April 2022

Fracture effectiveness evaluation has an important impact on the efficient exploration and development of ultra-deep fractured reservoirs. Based on the liquid production profile results collected during the development of the Keshen gas field and based on the traditional static evaluation of fracture density, opening and filling degree, the fracture effectiveness evaluation of ultra-deep reservoirs is carried out from the perspectives of fracture activity, fracture opening and fracture connectivity. The results show that the static characteristics, such as fracture density and fracture properties, are only some factors that determine the effectiveness of fractures. From the perspective of contributions to reservoir permeability, dynamic parameters such as fracture activity, fracture opening and fracture connectivity are the key factors in determining the effectiveness of fractures. Practice has proven that fractures with a high shear ratio, low stress environment and high connection with the fracture system around the well are the main seepage channels for oil and gas supply in the development process. The research results provide a scientific basis for well location deployment, optimization of reconstruction intervals and optimization of development schemes.
An Interactive Web Application Helps Students Explore Water Balance Concepts
Authors: Gannon John P. , McGuire Kevin J.
Published: April 2022

The concept of a water balance is a foundational topic in hydrology classrooms. While understanding and applying this concept is crucial to the introduction of more advanced topics, students often struggle to develop a thorough understanding of the relationships between components, assumptions, and limitations of a water balance. To aid students in developing a working understanding of a water balance, we developed a web application that runs a one dimensional Thornthwaite-type water balance at any of thousands of NOAA climate stations across the continental United States using the local soil-water storage capacity at the station location. Within the app, students can manipulate the soil-water storage capacity, latitude, temperature, and precipitation to better understand how it works and explore scenarios of land use, extreme weather, and climate change. The application is free and will run on any device that can open an internet browser window (laptops, chromebooks, smartphones, etc). Here we present the details of the model, functionality of the application, and link to several ready-made classroom activities. Finally, results from student surveys in two hydrology classrooms show that students may learn water balance concepts more effectively than traditional methods such as spreadsheet computations.
Factors Defining the Association Between Vitamin D and Testosterone in Males With Type 2 Diabetes and Hypogonadism
Authors: Hu Xin , Han Xue , Chen Yu , Xiang Pingping , Wei Xiao , Gong Tong , He Zhiwei , Su Yafeng , Chen Guofang , Liu Chao
Published: April 2022

Objective

This study aimed to evaluate Serum 25-hydroxyvitamin D (25[OH]D) levels in diabetic men with and without hypogonadism and figured out the potential factors influencing the connection between vitamin D and testosterone.

Methods

A total of 367 men with type 2 diabetes mellitus (T2DM) were investigated, including 254 men with normal gonadal function (Group 1) and 113 men with hypogonadism (Group 2). Men with hypogonadism were classified as either hypogonadotropic hypogonadism (Group 2a) or hypergonadotropic hypogonadism (Group 2b). Serum 25(OH)D levels were detected by liquid chromatography-tandem mass spectrometry in all cases. Morning total testosterone (TT), estradiol (E), dehydroepiandrosterone (DHEA), prolactin (PRL), sex hormone-binding globulin (SHBG), luteinizing hormone (LH), follicle-stimulating hormone (FSH), thyroid function, parathyroid and adrenal hormones, fasting blood glucose (FBG), fasting insulin (Fins) and hemoglobin A1c (HbA1c) were also assessed.

Results

The prevalence of hypovitaminosis D in men with T2DM was up to 96.46%. Serum 25(OH)D levels were significantly lower in men with hypogonadism than those with eugonadism (16.65 ± 6.44 ng/mL vs. 18.17 ± 6.17 ng/mL, P=0.033). The lowest 25(OH)D level was observed in Group 2a (16.22 ± 6.52 ng/mL). After adjustment for the selected factors, serum 25(OH)D concentrations were shown to be positively correlated with TT concentrations (r=0.137, P=0.032). The relationship between 25(OH)D and testosterone was altered by age, duration of T2DM, body mass index, and HbA1c. Serum 25(OH)D level was positively associated with serum TT level in men with age <60 years (r=0.180, P=0.003), or with duration≥5 years (r=0.186, P=0.013), or with body mass index (BMI)≥28kg/m2 (r=0.431, P=0.000), or with HbA1c≥9% (r=0.145, P=0.031).

Conclusions

These findings indicate that type 2 diabetes patients with hypogonadism have lower 25(OH)D levels than those without hypogonadism. There seems to be a positive association between the serum 25(OH)D and TT levels, which affected by age, duration, BMI, and HbA1c
A Preliminary Study on Infrared Thermograph of Metabolic Syndrome
Authors: Gao Meng-jiao , Xue Hui-zhong , Cai Rui , Jiang Bi-yao , Mi Bao-hong , Chen Zong-jun , Shi Yin-chun , Xiao Yong-hua , Zhang Wen-zheng
Published: April 2022

Objective

To explore the temperature distribution characteristics of the face, palms, feet and the trunk area of metabolic syndrome (MS) through infrared thermography (IRT) and provide evidence for the application of IRT in the assistant evaluation of MS population.

Methods

We collected thermographs of 184 participants (91 males, 93 females) and further divided participants of each gender into 4 groups according to the number of abnormal metabolic indexes. Mean temperatures of 6 Region of Interests (ROIs) (face, anterior trunk, bilateral palms and dorsum of feet) were calculated. Comparisons of the mean temperatures between genders, among groups and ROIs were carried out.

Results

Male participants had higher mean temperature in their face, palms (P<0.01) and dorsum of feet (P<0.05), and lower mean temperature in the anterior trunk (P<0.01). Female participants with MS had higher mean temperature in their palms and dorsum of feet (P<0.01) and lower mean temperature in the anterior trunk (P<0.01) than normal participants. Similar tendencies were shown in the mean temperature of the left palms and trunk of MS males. With the increase of the number of abnormal metabolic indexes, it seems that the mean temperature gradually increased in palms and dorsum of feet, and decreased in the anterior trunk.

Conclusion

The thermograph of MS exhibits certain characteristics. This may help reveal the correlations between Infrared thermography and metabolic disorders.
Transient Stability Analysis and Control of Distributed Photovoltaic Generators in the DC Distribution Network
Authors: He Hanghang , Xia Yanghong , Wei Wei , Yang Pengcheng
Published: April 2022

As dominant power sources, the safe and reliable operation of photovoltaic (PV) generators is crucial for the DC distribution network. This study analyzes the transient stability of PV generators under large disturbances and proposes a variable parameter control strategy to suppress the transient instability. First, the transient stability of the PV generators is analyzed using the proposed power–voltage evolution curve. It is found that the PV side easily suffers undervoltage faults during the transient process, which will cause instability of the system. Based on the revealed unstable mechanism, the variable parameter control is proposed to enhance the transient stability of PV generators. Finally, all the findings have been validated by hardware-in-loop tests.
Stratified Saline Flume Experiments on the Entrainment Process of the Atmospheric Convective Boundary Layer With Vertical Wind Shear
Authors: Li A. , Lin W. , Gao W. , Liu T. , Xia Y.
Published: April 2022

A stratified saline flume experimental apparatus was set up in this study to experimentally simulate the entrainment process of the atmospheric convective boundary layer with vertical wind shear, of which the entrainment characteristics are quite different from those of the shear-free convective boundary layer. Entrainment occurs at the interface of the flume inlet until the velocity difference between the upper and lower layers reaches 0.04 m/s, and a thin stable entrainment zone is formed at a 12zi distance from the flow inlet, where zi is the height of the entrainment zone. Shear in the entrainment zone induces the counter-gradient momentum transport process, and a series of large-scale vortices with a characteristic length of about (1.0–1.5)zi fills this region. The data analysis shows that the velocity difference and buoyancy flux of the bottom plume promote the occurrence of entrainment, while the density difference between the upper and lower layers inhibits it. The contribution of the shear effect to the entrainment process was introduced into the characteristic velocity scale, and a new scaling relation between the dimensionless thickness of the entrainment zone and the corrected Richardson number was obtained as Δz/zi = 1.17RiNC−1/2 from the experimental results, which agrees well with the available radar data and the numerical simulation data.
Thermodynamics and Kinetics of pH-dependent Dissolution of Sparingly Soluble Alkaline Earth Hydroxides in Source-Separated Human Urine Collected in Decentralised Sanitation Systems
Authors: Simha Prithvi , Deb Chinmoy Kanti , Randall Dyllon G. , Vinnerås Björn
Published: April 2022

Alkaline earth hydroxides are widely used in water and wastewater treatment. Within the emerging niche of source-separating sanitation, these chemicals have found a new application—to prevent urease-catalysed degradation of urea present in freshly excreted human urine. However, little is known about the dissolution behaviour of these hydroxides in biological fluids like human urine. Herein, we investigate the solubility of Mg(OH)2 and examine factors that govern its dissolution in different types of urine (real fresh urine, synthetic fresh urine, synthetic dephosphatised fresh urine and real fresh urine concentrated by CO2-free drying). We report experimentally determined as well as thermodynamically simulated data on Mg(OH)2 solubility, dissolution kinetics, and chemical speciation in urine. We find that it takes between 6 and 16 min for Mg(OH)2 to dissolve and the average solubility in real fresh urine at 25°C to be 650 mg L−1. We show that solubility is influenced mainly by concentration of organic compounds, soluble phosphate, and magnesium excreted in fresh urine. When fresh urine is supersaturated with Mg(OH)2, the pH increases to >10.5 and urease-catalysed degradation of urea is inhibited for >14 days. Removing 95% water present in urine increases the solubility of Mg(OH)2 to 16,240 mg L−1 but reduces pH to < 10. Because relative increase in Mg(OH)2 solubility decreases as more water is removed and the solubility is retrograde with respect to temperature, to increase the urine pH to >10 and prevent enzymatic ureolysis, the temperature must be kept < 29°C at 75% water removal and < 22°C at 95% water removal. We find this dissolution behaviour of Mg(OH)2 in concentrated urine solutions to be unlike other alkaline earth hydroxides. These findings have significant implications for the design of new sanitation systems that separately collect and recycle plant-essential nutrients present in human urine.
CRISPR-Mediated Activation of αV Integrin Subtypes Promotes Neuronal Differentiation of Neuroblastoma Neuro2a Cells
Authors: Riccardi Sara , Cingolani Lorenzo A. , Jaudon Fanny
Published: April 2022

Neuronal differentiation is a complex process whose dysfunction can lead to brain disorders. The development of new tools to target specific steps in the neuronal differentiation process is of paramount importance for a better understanding of the molecular mechanisms involved, and ultimately for developing effective therapeutic strategies for neurodevelopmental disorders. Through their interactions with extracellular matrix proteins, the cell adhesion molecules of the integrin family play essential roles in the formation of functional neuronal circuits by regulating cell migration, neurite outgrowth, dendritic spine formation and synaptic plasticity. However, how different integrin receptors contribute to the successive phases of neuronal differentiation remains to be elucidated. Here, we implemented a CRISPR activation system to enhance the endogenous expression of specific integrin subunits in anin vitromodel of neuronal differentiation, the murine neuroblastoma Neuro2a cell line. By combining CRISPR activation with morphological and RT-qPCR analyses, we show that integrins of the αV family are powerful inducers of neuronal differentiation. Further, we identify a subtype-specific role for αV integrins in controlling neurite outgrowth. While αVβ3 integrin initiates neuronal differentiation of Neuro2a cells under proliferative conditions, αVβ5 integrin appears responsible for promoting a complex arborization in cells already committed to differentiation. Interestingly, primary neurons exhibit a complementary expression pattern for β3 and β5 integrin subunits during development. Our findings reveal the existence of a developmental switch between αV integrin subtypes during differentiation and suggest that a timely controlled modulation of the expression of αV integrins by CRISPRa provides a means to promote neuronal differentiation.
MicroRNA Profiling of the Tears of Children With Vernal Keratoconjunctivitis
Authors: Syed Nazmul Huda , Shahidan Wan Nazatul Shima , Shatriah Ismail , Zunaina Embong
Published: April 2022

Vernal Keratoconjunctivitis (VKC) is a chronic conjunctival inflammatory condition that typically affects children. Extracellular microRNAs (miRNAs) are small noncoding RNA molecules, the expression of which is reported to regulate cellular processes implicated in several eye diseases. The aim of this preliminary study is to identify the miRNA expression profile in the tears of children with VKC vis-à-vis controls, and to statistically evaluate these miRNAs as potential diagnostic biomarkers of VKC. The study involved a VKC group and a control group. Tear specimens were collected using Schirmer’s strips. RNA was isolated using miRNeasy Micro kit and quantification was performed using an Agilent Bioanalyzer RNA 6000 Nano kit and Small RNA kit. miRNA profiling was performed using the Agilent microarray technique. A total of 51 miRNAs (48 upregulated and three downregulated) were differentially expressed in the tears of children with VKC and controls. The three most significantly upregulated miRNAs were hsa-miR-1229-5p, hsa-miR-6821-5p, and hsa-miR-6800-5p, and the three most significantly downregulated miRNAs were hsa-miR-7975, hsa-miR-7977, and hsa-miR-1260a. All the upregulated miRNAs are potential diagnostic biomarkers of VKC pending validation due to their larger discriminatory area under the curve (AUC) values. miRNA target prediction analysis revealed multiple overlapping genes that are known to play a role in conjunctival inflammation. We identified a set of differentially expressed miRNAs in the tears of children with VKC that may play a role in VKC pathogenesis. This study serves as the platform study for future miRNA studies that will provide a deeper understanding of the pathophysiology of VKC.
Novel miRNA-SSRs for Improving Seed Hardness Trait of Pomegranate (Punica granatum L.)
Authors: Patil Prakash Goudappa , Singh Nripendra Vikram , Bohra Abhishek , Jamma Shivani , N Manjunatha , C Venkatesh S. , Karuppannan Dhinesh Babu , Sharma Jyotsana , Marathe Rajiv A.
Published: April 2022

Present research discovered novel miRNA-SSRs for seed type trait from 761 potential precursor miRNA sequences of pomegranate. SSR mining and BLASTx of the unique sequences identified 69 non-coding pre-miRNA sequences, which were then searched for BLASTn homology against Dabenzi genome. Sixty three true pri-miRNA contigs encoding 213 pre-miRNAs were predicted. Analysis of the resulting sequences enabled discovery of SSRs within pri-miRNA (227) and pre-miRNA sequences (79). A total of 132 miRNA-SSRs were developed for seed type trait from 63 true pri-miRNAs, of which 46 were specific to pre-miRNAs. Through ePCR, 123 primers were validated and mapped on eight Tunisia chromosomes. Further, 80 SSRs producing specific amplicons were ePCR-confirmed on multiple genomesi.e.Dabenzi, Taishanhong, AG2017 and Tunisia, yielding a set of 63 polymorphic SSRs (polymorphism information content ≥0.5). Of these, 32 miRNA-SSRs revealed higher polymorphism level (89.29%) when assayed on six pomegranate genotypes. Furthermore, target prediction and network analysis suggested a possible association of miRNA-SSRsi.e.miRNA_SH_SSR69, miRNA_SH_SSR36, miRNA_SH_SSR103, miRNA_SH_SSR35 and miRNA_SH_SSR53 with seed type trait. These miRNA-SSRs would serve as important genomic resource for rapid and targeted improvement of seed type trait of pomegranate.
Change of Left Ventricular Myocardial Contractility in Speckle Tracking Echocardiography After Transjugular Intrahepatic Portosystemic Shunt Predicts Survival
Authors: Jansen Christian , Nordmann Pia , Cremonese Carla , Praktiknjo Michael , Chang Johannes , Lehmann Jennifer , Thomas Daniel , Nickenig Georg , Weber Marcel , Stöhr Elisabeth , Öztürk Can , Zachoval Christian , Hammerstingl Christoph , Strassburg Christian P. , Meyer Carsten , Trebicka Jonel
Published: April 2022

Background

Left ventricular global longitudinal strain (LV-GLS) has been shown to better reflect the left cardiac contractility in cirrhosis than other investigations and might bear prognostic value. The aim of this study was to investigate the evolution of myocardial contractility assessed by speckle tracking echocardiography (STE) after transjugular intrahepatic portosystemic shunt (TIPS) placement and its prognostic value in outcome.

Methods

In this study, 206 (126 males) patients with liver cirrhosis receiving TIPS were included. In all study patients, conventional transthoracic echocardiography (TTE) was performed before and in the first weeks after TIPS placement to assess left and right ventricular volume, planar and functional parameters. Also, LV-GLS was measured by STE to assess left ventricular contractility as surrogate for myocardial dysfunction. Hemodynamic and clinical parameters were assessed before TIPS and during follow-up.

Results

As expected, most conventional parameters of TTE showed a significant change after TIPS placement. However, neither the absolute values, nor the changes of conventional cardiac parameters of TTE before and after TIPS insertion were associated with survival. By contrast, an increase in contractility of more than 20% using STE after TIPS was an independent predictor of mortality.

Conclusion

These results demonstrate that an increase of left ventricular contractility of more than 20% after TIPS insertion is an independent predictor of survival and this may identify patients at risk and in need of closer follow-up care.
SARS-CoV-2 Spike Protein Expression In Vitro and Hematologic Effects in Mice Vaccinated With AZD1222 (ChAdOx1 nCoV-19)
Authors: Stebbings Richard , Jones Christopher , Cotton Peter , Armour Gillian , Maguire Shaun , Skellett Vicky , Tang Chi-Man , Goodman Joanne , Brady Tyler , Takahashi Virginia , Daunt Andrew , Lapointe Jean-Martin , Cohen Taylor S.
Published: April 2022

Severe COVID-19 can be associated with a prothrombotic state, increasing risk of morbidity and mortality. The SARS-CoV-2 spike glycoprotein is purported to directly promote platelet activation via the S1 subunit and is cleaved from host cells during infection. High plasma concentrations of S1 subunit are associated with disease progression and respiratory failure during severe COVID-19. There is limited evidence on whether COVID-19 vaccine-induced spike protein is similarly cleaved and on the immediate effects of vaccination on host immune responses or hematology parameters. We investigated vaccine-induced S1 subunit cleavage and effects on hematology parameters using AZD1222 (ChAdOx1 nCoV-19), a simian, replication-deficient adenovirus-vectored COVID-19 vaccine. We observed S1 subunit cleavage in vitro following AZD1222 transduction of HEK293x cells. S1 subunit cleavage also occurred in vivo and was detectable in sera 12 hours post intramuscular immunization (1x1010 viral particles) in CD-1 mice. Soluble S1 protein levels decreased within 3 days and were no longer detectable 7–14 days post immunization. Intravenous immunization (1x109 viral particles) produced higher soluble S1 protein levels with similar expression kinetics. Spike protein was undetectable by immunohistochemistry 14 days post intramuscular immunization. Intramuscular immunization resulted in transiently lower platelet (12 hours) and white blood cell (12–24 hours) counts relative to vehicle. Similarly, intravenous immunization resulted in lower platelet (24–72 hours) and white blood cell (12–24 hours) counts, and increased neutrophil (2 hours) counts. The responses observed with either route of immunization represent transient hematologic changes and correspond to expected innate immune responses to adenoviral infection.
Role of Cellular Metabolism in the Formation of Neutrophil Extracellular Traps in Airway Diseases
Authors: Morán Gabriel , Uberti Benjamín , Quiroga John
Published: April 2022

Neutrophil extracellular traps (NETs) are a recently described mechanism of neutrophils that play an important role in health and disease. NETs are an innate defense mechanism that participate in clearance of pathogens, but they may also cause collateral damage in unrelated host tissues. Neutrophil dysregulation and NETosis occur in multiple lung diseases, such as pathogen-induced acute lung injury, pneumonia, chronic obstructive pulmonary disease (COPD), severe asthma, cystic fibrosis, and recently, the novel coronavirus SARS-CoV-2. More recently, research into immunometabolism has surged due to the possibility of reprogramming metabolism in order to modulate immune functions. The present review analyzes the different metabolic pathways associated with NETs formation, and how these impact on pathologies of the airways.
Complement-Mediated Neutralisation Identified in Ebola Virus Disease Survivor Plasma: Implications for Protection and Pathogenesis
Authors: Mellors Jack , Tipton Tom , Fehling Sarah Katharina , Akoi Bore Joseph , Koundouno Fara Raymond , Hall Yper , Hudson Jacob , Alexander Frances , Longet Stephanie , Taylor Stephen , Gorringe Andrew , Magassouba N’Faly , Konde Mandy Kader , Hiscox Julian , Strecker Thomas , Carroll Miles
Published: April 2022

The 2013–2016 Ebola virus (EBOV) epidemic in West Africa was unprecedented in case numbers and fatalities, and sporadic outbreaks continue to arise. Antibodies to the EBOV glycoprotein (GP) are strongly associated with survival and their use in immunotherapy is often initially based on their performance in neutralisation assays. Other immune effector functions also contribute to EBOV protection but are more complex to measure. Their interactions with the complement system in particular are comparatively under-researched and commonly excluded from cellular immunoassays. Using EBOV convalescent plasma samples from the 2013–2016 epidemic, we investigated antibody and complement-mediated neutralisation and how these interactions can influence immunity in response to EBOV-GP and its secreted form (EBOV-sGP). We defined two cohorts: one with low-neutralising titres in relation to EBOV-GP IgG titres (LN cohort) and the other with a direct linear relationship between neutralisation and EBOV-GP IgG titres (N cohort). Using flow cytometry antibody-dependent complement deposition (ADCD) assays, we found that the LN cohort was equally efficient at mediating ADCD in response to the EBOV-GP but was significantly lower in response to the EBOV-sGP, compared to the N cohort. Using wild-type EBOV neutralisation assays with a cohort of the LN plasma, we observed a significant increase in neutralisation associated with the addition of pooled human plasma as a source of complement. Flow cytometry ADCD was also applied using the GP of the highly virulent Sudan virus (SUDV) of theSudan ebolavirusspecies. There are no licensed vaccines or therapeutics against SUDV and it overlaps in endemicity with EBOV. We found that the LN plasma was significantly less efficient at cross-reacting and mediating ADCD. Overall, we found a differential response in ADCD between LN and N plasma in response to variousEbolavirusglycoproteins, and that these interactions could significantly improve EBOV neutralisation for selected LN plasma samples. Preservation of the complement system in immunoassays could augment our understanding of neutralisation and thus protection against infection
Identification of a Tumor Immunological Phenotype-Related Gene Signature for Predicting Prognosis, Immunotherapy Efficacy, and Drug Candidates in Hepatocellular Carcinoma
Authors: Tang Yuqin , Guo Chengbin , Yang Zhao , Wang Yumei , Zhang Yongqiang , Wang Dong
Published: April 2022

Hepatocellular carcinoma (HCC) is the predominant subtype of primary liver cancer and represents a highly heterogeneous disease, making it hard to predict the prognosis and therapy efficacy. Here, we established a novel tumor immunological phenotype-related gene index (TIPRGPI) consisting of 11 genes by Univariate Cox regression and the least absolute shrinkage and selection operator (LASSO) algorithm to predict HCC prognosis and immunotherapy response. TIPRGPI was validated in multiple datasets and exhibited outstanding performance in predicting the overall survival of HCC. Multivariate analysis verified it as an independent predictor and a TIPRGPI-integrated nomogram was constructed to provide a quantitative tool for clinical practice. Distinct mutation profiles, hallmark pathways, and infiltration of immune cells in tumor microenvironment were shown between the TIPRGPI high and low-risk groups. Notably, significant differences in tumor immunogenicity and tumor immune dysfunction and exclusion (TIDE) were observed between the two risk groups, suggesting a better response to immune checkpoint blockade (ICB) therapy of the low-risk group. Besides, six potential drugs binding to the core target of the TIPRGPI signature were predicted via molecular docking. Taken together, our study shows that the proposed TIPRGPI was a reliable signature to predict the risk classification, immunotherapy response, and drugs candidate with potential application in the clinical decision and treatment of HCC. The novel “TIP genes”-guided strategy for predicting the survival and immunotherapy efficacy, we reported here, might be also applied to more cancers other than HCC.
The Missing Link in Correlates of Protective Tuberculosis Immunity: Recognizing the Infected Cell
Authors: Lewinsohn David Michael , Lewinsohn Deborah Anne
Published: April 2022

For most vaccination studies, the assessment of vaccine-induced CD4+and CD8+T cells has relied upon the measurement of antigen-specific polyfunctional cells, typically using recombinant antigen or peptide pools. However, this approach leaves open the question as to whether or not these cells are responsive to the Mtb-infected cell within the context of Mtb infection and hence leaves open the possibility that a key parameter of vaccine immunogenicity may be overlooked. In this review, we discuss the case that these measurements almost certainly over-estimate the capacity of both CD4+and CD8+T cells to recognize the Mtb-infected cell.
Periodontitis-Derived Dark-NETs in Severe Covid-19
Authors: Vitkov Ljubomir , Knopf Jasmin , Krunić Jelena , Schauer Christine , Schoen Janina , Minnich Bernd , Hannig Matthias , Herrmann Martin
Published: April 2022

The frequent severe COVID-19 course in patients with periodontitis suggests a link of the aetiopathogenesis of both diseases. The formation of intravascular neutrophil extracellular traps (NETs) is crucial to the pathogenesis of severe COVID-19. Periodontitis is characterised by an increased level of circulating NETs, a propensity for increased NET formation, delayed NET clearance and low-grade endotoxemia (LGE). The latter has an enormous impact on innate immunity and susceptibility to infection with SARS-CoV-2. LPS binds the SARS-CoV-2 spike protein and this complex, which is more active than unbound LPS, precipitates massive NET formation. Thus, circulating NET formation is the common denominator in both COVID-19 and periodontitis and other diseases with low-grade endotoxemia like diabetes, obesity and cardiovascular diseases (CVD) also increase the risk to develop severe COVID-19. Here we discuss the role of propensity for increased NET formation, DNase I deficiency and low-grade endotoxaemia in periodontitis as aggravating factors for the severe course of COVID-19 and possible strategies for the diminution of increased levels of circulating periodontitis-derived NETs in COVID-19 with periodontitis comorbidity.
The Adipose Tissue Macrophages Central to Adaptive Thermoregulation
Authors: Rahman Md. Shamim , Jun Heejin
Published: April 2022

White fat stores excess energy, and thus its excessive expansion causes obesity. However, brown and beige fat, known as adaptive thermogenic fat, dissipates energy in the form of heat and offers a therapeutic potential to counteract obesity and metabolic disorders. The fat type-specific biological function is directed by its unique tissue microenvironment composed of immune cells, endothelial cells, pericytes and neuronal cells. Macrophages are major immune cells resident in adipose tissues and gained particular attention due to their accumulation in obesity as the primary source of inflammation. However, recent studies identified macrophages’ unique role and regulation in thermogenic adipose tissues to regulate energy expenditure and systemic energy homeostasis. This review presents the current understanding of macrophages in thermogenic fat niches with an emphasis on discrete macrophage subpopulations central to adaptive thermoregulation.