bluuebunny/crossref_metadata_2025 huggingface dataset:
Professional Sports Trainers' Burnout in Fully Online and Blended Classes: Innovative Approaches in Physical Education and Sports Training
Authors: Nguyễn Hoàng Minh Thuận , Ɖỗ Thị Hoài Thu' , Nguyễn Nhật Quang
Published: June 2022

The COVID-19 pandemic has forced many educational institutions worldwide to establish emergency remote teaching systems. Although online teaching has long been applied in many other subjects, online sports training is still under-researched in developing countries like Vietnam. In Vietnam, sports trainers are innovatively making many efforts to teach sports online amidst such a once-in-many-generations event. Particularly, a gym center chain has been offering two special formats of online courses utilizing virtual reality (VR) and three-dimensional (3D) technologies, namely, fully online and blended courses. The first format comprises 50% asynchronous sessions using VR and 3D technologies to provide trainees with theoretical knowledge and 50% offline sessions for practical skills training. The second format also includes 50% asynchronous sessions using the same technologies; however, the training for practical skills is conducted via an e-conferencing platform (Zoom). Fortunately, the blended courses have attracted significant attention from many sports trainees. However, as sports trainers in Vietnam had minimal opportunities to teach online before this epidemic, it is likely that, while teaching these courses, they can encounter moments of burnout, which comprises three dimensions, such as exhaustion, cynicism, and low professional efficacy. Thus, we aim to investigate factors that affected each dimension of burnout among sports trainers, using the mixed-method approach with questionnaires and focus-group interviews within this study. This study suggests practical pedagogical implications for sports trainers and administrators to curb stress and burnout in online sports training courses in times of crisis.
A New MAMLD1 Variant in an Infant With Microphallus and Hypospadias With Hormonal Pattern Suggesting Partial Hypogonadotropic Hypogonadism—Case Report
Authors: Yeste Diego , Aguilar-Riera Cristina , Canestrino Gennaro , Fernández-Alvarez Paula , Clemente María , Camats-Tarruella Núria
Published: June 2022

MAMLD1 (X chromosome) is one of the recognized genes related to different sex development. It is expressed in testis and ovaries and seems to be involved in fetal sex development and in adult reproductive function, including testosterone biosynthesis. However, its exact role remains unclear. Over 40 genetic variants have been described, mainly in male individuals and mostly associated with hypospadias. Although MAMLD1 has been shown to regulate the expression of the steroidogenic pathway, patients with MAMLD1 variants mostly show normal gonadal function and normal testosterone levels. Here we describe a patient (46,XY) with hypospadias and microphallus, with low testosterone and dihydrotestosterone (DHT) levels, and with inappropriately low values of luteinizing hormone (LH) during minipuberty. This hormonal pattern was suggestive of partial hypogonadotropic hypogonadism. A stimulation test with hCG (4 months) showed no significant increase in both testosterone and dihydrotestosterone concentrations. At 5 months of age, he was treated with intramuscular testosterone, and the penis length increased to 3.5 cm. The treatment was stopped at 6 months of age. Our gonadal function massive-sequencing panel detected a previously unreported nonsense variant in the MAMLD1 gene (c.1738C>T:p.Gln580Ter), which was classified as pathogenic. This MAMLD1 variant, predicting a truncated protein, could explain his genital phenotype. His hormonal profile (low testosterone, dihydrotestosterone, and LH concentrations) together with no significant increase of testosterone and DHT plasma concentrations (hCG test) highlight the potential role of this gene in the biosynthesis of testosterone during the fetal stage and minipuberty of the infant. Besides this, the LH values may suggest an involvement of MAMLD1 in the LH axis or a possible oligogenesis. It is the first time that a decrease in DHT has been described in a patient with an abnormal MAMLD1.
Central Gαi2 Protein Mediated Neuro-Hormonal Control of Blood Pressure and Salt Sensitivity
Authors: Amraei Razie , Moreira Jesse D. , Wainford Richard D.
Published: June 2022

Hypertension, a major public health issue, is estimated to contribute to 10% of all deaths worldwide. Further, the salt sensitivity of blood pressure is a critical risk factor for the development of hypertension. The hypothalamic paraventricular nucleus (PVN) coordinates neuro-hormonal responses to alterations in plasma sodium and osmolality and multiple G Protein-Coupled Receptors (GPCRs) are involved in fluid and electrolyte homeostasis. In acute animal studies, our laboratory has shown that central Gαi/o subunit protein signal transduction mediates hypotensive and bradycardic responses and that Gz/q, proteins mediate the release of arginine vasopressin (AVP) and subsequent aquaretic responses to acute pharmacological stimuli. Extending these studies, our laboratory has shown that central Gαi2 proteins selectively mediate the hypotensive, sympathoinhibitory and natriuretic responses to acute pharmacological activation of GPCRs and in response to acute physiological challenges to fluid and electrolyte balance. In addition, following chronically elevated dietary sodium intake, salt resistant rats demonstrate site-specific and subunit-specific upregulation of Gαi2 proteins in the PVN, resulting in sympathoinhibition and normotension. In contrast, chronic dietary sodium intake in salt sensitive animals, which fail to upregulate PVN Gαi2 proteins, results in the absence of dietary sodium-evoked sympathoinhibition and salt sensitive hypertension. Using in situ hybridization, we observed that Gαi2 expressing neurons in parvocellular division of the PVN strongly (85%) colocalize with GABAergic neurons. Our data suggest that central Gαi2 protein-dependent responses to an acute isotonic volume expansion (VE) and elevated dietary sodium intake are mediated by the peripheral sensory afferent renal nerves and do not depend on the anteroventral third ventricle (AV3V) sodium sensitive region or the actions of central angiotensin II type 1 receptors. Our translational human genomic studies have identified three G protein subunit alpha I2 (GNAI2) single nucleotide polymorphisms (SNPs) as potential biomarkers in individuals with salt sensitivity and essential hypertension. Collectively, PVN Gαi2 proteins-gated pathways appear to be highly conserved in salt resistance to counter the effects of acute and chronic challenges to fluid and electrolyte homeostasis on blood pressure via a renal sympathetic nerve-dependent mechanism.
The Relationship Between Pre-Operative Glycosylated Haemoglobin and Opioid Consumption After Caesarean Section in Women With Gestational Diabetes Mellitus
Authors: Yang Chen , Li Yue , Hu Jianying , Wu Jiangnan , Huang Shaoqiang
Published: June 2022

Introduction

Women with Gestational diabetes mellitus (GDM) had a higher need and consumption of analgesics than women without GDM. The preoperative level of HbA1c was associated with the postoperative consumption for analgesics in diabetic patients. This prospective observational study go further to investigate the relationship between the pre-operative HbA1c and the post-operative consumption for analgesics in women with GDM.

Methods

Women with GDM and a singleton pregnancy undergoing elective cesarean section under combined spinal-epidural anaesthesia were divided into two groups based on pre-operative HbA1c: group HbA1c < 6% and group HbA1c ≥ 6%. Analgesics consumption, number of patient-controlled analgesia (PCA) compression, and pain scores in 6 hours and 24 hours post-operation were compared between the two groups. Then Pearson’s correlation coefficient and a stepwise multivariate linear regression were performed to investigate possible independentpredictors of post-operative 24-hour sufentanil consumption.

Results

Analgesics consumption was significantly lower (18.8 ± 0.4 vs 23.2 ± 4.3; 82.7 ± 2.4 vs 115.8 ± 17.4, P < 0.001), and number of PCA compressions was significantly less frequent (1 [1-2] vs 3 [1-5]; 5 [3-7] vs 7 [3-15], P < 0.001), and in group HbA1c < 6% than in group HbA1c ≥ 6% in 6 hours and 24 hours post-operation.The univariate analysis showed that sufentanil consumption at 24 hours post-operation was significantly related to pre-operative HbA1c (r = 0.338, P < 0.001) and parity (r = 0.184, P = 0.03) and was related to blood glucose management methods (r = 0.172, P = 0.043). Multivariate linear regression analysis showed that HbA1c was the independent factor related to post-operative 24-hour sufentanil consumption (adjusted r2 = 0.246, P < 0.001)

Conclusions

This study demonstrated that in pregnant women with GDM, the pre-operative HbA1c is independently related to the need for and consumption of analgesics in 24 hours after CS.
Nomogram for Quantitatively Estimating the Risk of Fibrosis Progression in Type 2 Diabetic Patients With Nonalcoholic Fatty Liver Disease: A Pilot Study
Authors: Xia Jinying , Jin Guang , Hua Qifeng , Cui Shihan , Li Jianhui
Published: June 2022

Background

Correct identification of the fibrosis progression risk is a critical step in the management of patients with type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD), because liver fibrosis, especially advanced liver fibrosis, is difficult to reverse. However, the progression of liver fibrosis is typically unnoticeable, leading to many patients failing to adhere to long-term therapeutic interventions. Reliable clinical tools for the quantification of the fibrosis progression risk may have effects on following long-term therapeutic recommendations to avoid further liver injury.

Objective

This study aims to develop a nomogram for quantitatively estimating the risk of fibrosis progression in T2DM patients with NAFLD during lifestyle intervention.

Methods

A total of 432 medical records of T2DM patients with NAFLD were retrospectively analyzed in this study. We divided patients into the progression and no-progression groups according to whether the value of liver stiffness measurement (LSM) increased by > 2 kPa at the last visit. The independent factors associated with the fibrosis progression, which were screened by univariate and multivariate Logistic regression, constituted the nomogram to determine the likelihood of fibrosis progression in T2DM patients with NAFLD.

Results

Sixty-five of the 432 individuals (15%) were found to have fibrosis progression. Changes in body mass index [odds ratio (OR) = 1.586], glycosylated hemoglobin A1c (OR = 6.636), alanine aminotransferase (OR = 1.052), and platelet counts (OR = 0.908) were independently associated with fibrosis progression (all P < 0.05) and functioned as components of the newly developed nomogram. It showed satisfied discrimination and calibration after 1,000 bootstrapping. The DCA indicated that the nomogram yielded clinical net benefit when the threshold probability was < 0.8.

Conclusion

We developed a nomogram incorporating dynamic alterations in clinical features to estimate the risk of fibrosis progression in T2DM patients with NAFLD, which aids the patients’ compliance with long-term life interventions while allowing for prompt intervention adjustments.
The Role of Kisspeptin in the Control of the Hypothalamic-Pituitary-Gonadal Axis and Reproduction
Authors: Xie Qinying , Kang Yafei , Zhang Chenlu , Xie Ye , Wang Chuxiong , Liu Jiang , Yu Caiqian , Zhao Hu , Huang Donghui
Published: June 2022

The discovery of kisspeptin as a critical central regulatory factor of GnRH release has given people a novel understanding of the neuroendocrine regulation in human reproduction. Kisspeptin activates the signaling pathway by binding to its receptor kisspeptin receptor (KISS1R) to promote GnRH secretion, thereby regulating the hypothalamic-pituitary-gonadal axis (HPG) axis. Recent studies have shown that kisspeptin neurons located in arcuate nucleus (ARC) co-express neurokinin B (NKB) and dynorphin (Dyn). Such neurons are called KNDy neurons. KNDy neurons participate in the positive and negative feedback of estrogen to GnRH secretion. In addition, kisspeptin is a key factor in the initiation of puberty, and also regulates the processes of female follicle development, oocyte maturation, and ovulation through the HPG axis. In male reproduction, kisspeptin also plays an important role, getting involved in the regulation of Leydig cells, spermatogenesis, sperm functions and reproductive behaviors. Mutations in the KISS1 gene or disorders of the kisspeptin/KISS1R system may lead to clinical symptoms such as idiopathic hypogonadotropic hypogonadism (iHH), central precocious puberty (CPP) and female infertility. Understanding the influence of kisspeptin on the reproductive axis and related mechanisms will help the future application of kisspeptin in disease diagnosis and treatment. In this review, we critically appraise the role of kisspeptin in the HPG axis, including its signaling pathways, negative and positive feedback mechanisms, and its control on female and male reproduction.
Parametric Analysis of a Universal Isotherm Model to Tailor Characteristics of Solid Desiccants for Dehumidification
Authors: Burhan Muhammad , Chen Qian , Shahzad Muhammad Wakil , Ja M Kum , Ng Kim Choon
Published: June 2022

Cooling has a significant share in energy consumption, especially in hot tropical regions. The conventional mechanical vapor compression (MVC) cycle, widely used for air-conditioning needs, has high energy consumption as air is cooled down to a dew point to remove the moisture. Decoupling the latent cooling load through dehumidification from the sensible cooling load can significantly improve the energy requirement for air-conditioning applications. Solid desiccants have shown safe and reliable operation against liquid desiccants, and several configurations of solid desiccants dehumidifiers are studied to improve their performance. However, the characteristics of solid desiccants are critical for the performance and overall operation of the dehumidifier. The properties of every desiccant depend upon its porous adsorbing surface characteristics. Hence, it has an optimum performance for certain humid conditions. Therefore, for a better dehumidification performance in a specific tropical region, the solid desiccant must have the best performance, according to the humidity range of that region. In this article, a theoretical methodology has been discussed to help the industry and chemists to understand the porous structural properties of adsorbent surfaces needed to tune the material performance for a particular humidity value before material synthesis.
Two-Stage Robust Optimal Scheduling of “Nearly-Zero-Carbon Park” Considering the Synergy of Waste Disposal and Carbon Capture Gas-Fired Power Plants
Authors: Yao Zongjun , Zhang Tieyan , Zhao Yan
Published: June 2022

Aiming at the demand characteristics of “Nearly-zero Carbon Parks" (NZCP) powered by all renewable energy for low-carbon emissions and waste reduction, a NZCP topology and a two-stage robust optimal scheduling model based on the Carbon Capture Gas-fired Power Plant (CCGPP)-Power to Gas(P2G)-Waste Disposal (WD) collaborative model are proposed in this paper. First, the relationship between WD, CCGPP and energy supply and demand that can be generated from renewable energy is studied, and according to the system energy regulation requirements, the energy flexibility of residential loads, small industrial loads and electric vehicles are considered, and the NZCP mathematical model based on the CCGPP-P2G-WD collaborative model is established. Secondly, NZCP energy supply and demand characteristics are studied, and an energy coordination model for NZCP energy conversion and storage powered by 100% renewable energy is established. Then, wind power, photovoltaic power, and combined demand response uncertainties are considered, and the NZCP two-stage robust hybrid optimal dispatch model is established based on second-order cone relaxation and dual theory. Finally, the simulation analysis is carried out based on the operation data of the integrated energy system of a park in a certain area in northern my country. The simulation results show that the proposed two-stage robust optimal scheduling model of NZCP coordinated with WD and CCGPP can effectively improve the economy of the system at a higher energy balance level, improve the absorption capacity of renewable energy, and provide better multi-time scale energy regulation characteristics for NZCP with a larger energy supply scale.
Population Density: An Underlying Mechanism Between Road Transportation and Environmental Quality
Authors: Din Ashraf Ud , Ming Jian , Vega-Muñoz Alejandro , Salazar Sepúlveda Guido , Contreras-Barraza Nicolás
Published: June 2022

Mounting degradation in the environmental quality (EQL), specifically from the transport industry, is a big threat and challenge for sustainable development. The transport sector’s emission has gained researchers’ attention on climate change and transportation because of its increasing share in global emission. This study, thus, aims to analyze the links among road infrastructure (RIN), road transport energy consumption (RTEC), and environmental quality with the moderating role of population density (PDN). The study has used a dataset of five South Asian countries from 1971 to 2014. The study applies the Breusch–Pagan LM test to identify the issue of cross-sectional dependence. CIPS (second-generation unit root test) is applied to check the stationarity properties of the data, whereas the Westerlund (Oxf. Bul. Econ. Stat., 2007, 69 (6), 709–748) co-integration test is used to confirm the long-run association among the variables. Moreover, a fully modified ordinary least square (FMOLS) model is applied to analyze the effect that road transportation has on environmental quality. The study finds a positive effect of road infrastructure, road density (RDN), energy intensity (EIN), and road transport energy consumption on transport-generated emissions, which indicates that road transportation is harmful to environmental quality. Our results confirm the significant moderating role of population density in strengthening the relations of road infrastructure, road transport energy consumption, and environmental quality. It is concluded that population density works as a bridge between road infrastructure, road transport energy consumption, and environmental quality, which helps capture a strong impact of road transportation. We offer the planners of road transportation with a novel and practical approach to examine population density changes policy in the growing countries to analyze the environmental quality.
Exploring the Dynamic Relationship Between Energy Efficiency, Trade, Economic Growth, and CO2 Emissions: Evidence From Novel Fourier ARDL Approach
Authors: Liu Shuaibin , Durani Farah , Syed Qasim Raza , Haseeb Mohammad , Shamim Juhi , Li Zaijun
Published: June 2022

Climate change, energy security, and volatile energy prices have been emerging as eminent threats worldwide. To overcome these concerns, energy efficiency could play a positive role. Hence, this study probes whether energy efficiency curbs CO2 emissions in the US, while controlling for trade, economic growth, and population. We use the Fourier-ADF and Fourier-LM tests to discern the unit-roots. Moreover, to render reliable findings, we rely on the novel Fourier ARDL model. The study divulges that energy efficiency plunges emissions in the long- and short-run. In particular, a 1% upsurge in energy efficiency impedes emissions by about 0.37% and 1.07% during the long- and short-term, respectively. Moreover, population and economic growth escalate emissions whether it is long- or short-run. Next, we document that trade upsurges emissions in the long-run. Also, we perform two types of sensitivity analysis to test whether our key results remain the same across different models/methods. Finally, we suggest escalating energy efficiency through investment and technological advancement. Moreover, import tariffs on renewables should be plunged while there should be relatively high tariffs on non-renewables.
A Comparison Between Omicron and Earlier COVID-19 Variants' Disease Severity in the Milan Area, Italy
Authors: Consolazio David , Murtas Rossella , Tunesi Sara , Lamberti Anna , Senatore Sabrina , Faccini Marino , Russo Antonio Giampiero
Published: June 2022

Background

In the context of the fourth wave of the COVID-19 pandemic in Italy, which occurred in correspondence with the outbreak of the Omicron variant, it became fundamental to assess differences in the risk of severe disease between the Omicron variant and the earlier SARS-CoV-2 variants that were still in circulation despite Omicron becoming prevalent.

Methods

We collected data on 2,267 genotyped PCR-positive swab tests and assessed whether the presence of symptoms, risk of hospitalization, and recovery times were significantly different between Omicron and the earlier variants. Multivariable models adjusted for sex, age class, citizenship, comorbidities, and symptomatology allowed assessing the difference in outcomes between Omicron and the earlier variants according to vaccination status and timing of administration.

Results

Compared to the earlier variants in the same period, Omicron was less symptomatic, resulted in fewer hospital admissions for those who were unvaccinated and for those who were already immunized after the booster dose, and was associated with quicker recovery, yet not in subjects with three vaccination doses.

Conclusion

Despite being milder, Omicron's higher transmissibility and vaccine resistance should not lead to underrating its damage potential, especially with regard to hospital and health service saturation.
Recombinant Full-Length Hepatitis C Virus E1E2 Dimer Elicits Pangenotypic Neutralizing Antibodies
Authors: Lin Tianli , Chi Xiaojing , Liu Xiuying , Pan Shengnan , Chen Wenfang , Duan Huarui , Zhang Xinhui , Yang Wei
Published: June 2022

An effective prophylactic vaccine would be beneficial for controlling and eradicating hepatitis C virus (HCV) infections. However, the high diversity across HCV genotypes is a major challenge for vaccine development. Selection of the appropriate immunogen is critical to elicit broad HCV neutralizing antibodies (NAbs). To increase the antigenic coverage of heterodimer glycoproteins, we designed and produced recombinant E1E2 antigens for genotypes 1a/1b/2a/3a/6a from an IgG Fc-tagged precursor protein in FreeStyle 293-F cells. The recombinant E1 and E2 antigens were localized and associated with the endoplasmic reticulum and co-purified from membrane extracts. By examining the interactions with HCV entry co-receptors and the blockade of HCV infection, we found that these purified Fc-E1E2 proteins displayed correct folding and function. Mouse immunization results showed that each recombinant E1E2 antigen could elicit a pangenotypic antibody response to itself and other genotypes. We also found that the pentavalent formula triggered a relatively higher and more uniform NAb titer and T cell response than monovalent antigens. Taken together, our findings may provide a useful strategy for the vaccine development of HCV and other viruses with highly heterogeneous surface glycoproteins.
Natural Killer Cells Induce CD8+ T Cell Dysfunction via Galectin-9/TIM-3 in Chronic Hepatitis B Virus Infection
Authors: Liu Siyu , Xu Chang , Yang Fan , Zong Lu , Qin Yizu , Gao Yufeng , Su Qian , Li Tuantuan , Li Ye , Xu Yuanhong , Zheng Meijuan
Published: June 2022

The antiviral response of natural killer (NK) cells and CD8+ T cells is weak in patients with chronic hepatitis B (CHB) infection. However, the specific characteristics of these cells and the association between NK cells and CD8+ T cell dysfunction is not well known. In this study, higher galectin-9 (Gal-9) expression was observed in circulating NK cells from CHB patients than from healthy controls and was found to contribute to NK cell dysfunction. In addition, circulating CD8+ T cells showed obvious dysfunction and overexpressed TIM-3, the natural receptor of Gal-9, during active CHB infection. Gal-9+ and Gal-9- NK cells from active CHB patients were sorted and cocultured with autologous CD8+ T cells. The proportion of tetramer+CD8+ T cells and the cytokines production of CD8+ T cells were lower after cocultivation with Gal-9+ than with Gal-9- NK cells. We showed that in vitro depletion of NK cells increased circulating hepatitis B virus (HBV)-specific CD8+ T cell responses in patients with active CHB infection. Because Gal-9 is increased in the serum of CHB patients, CD8+ T cells were sorted and cultured with exogenous Gal-9, resulting in lower IFN-γ, TNF-α, CD107a, and granzyme B levels, decreased expression of the activation receptor CD69, increased expression of TIM-3, and a high percentage of early apoptotic CD8+ T cells. Blocking Gal-9 or TIM-3 in vitro in a culture of peripheral blood mononuclear cells (PBMCs) stimulated with HBV peptide from active CHB patients restored CD8+ T cell function. However, blocking Gal-9 in vitro after removal of NK cells from PBMCs did not rescue CD8+ T cells exhaustion. Furthermore, NK and CD8+ T cells from active CHB patients were sorted and cocultured in vitro, and the exhaustion of CD8+ T cells were alleviated after blocking Gal-9 or TIM-3. In summary, overexpression of Gal-9 on NK cells, which interacts with TIM-3+CD8+ T cells and likely contributes to antiviral CD8+ T cell dysfunction, may be a potential target for the treatment of CHB patients.
Multicomponent Precipitation and Strengthening in Intermetallic-Strengthened Alloys
Authors: Fang J.Y.C. , Liu W.H. , Yang T. , Wu Y. , Jiao Z.B.
Published: June 2022

Advanced structural materials with superior mechanical properties are of technological importance for industrial applications. Multicomponent precipitation provides a potential approach for designing high-performance alloys and has been receiving increasing attention from both academia and industry. In this Perspective, we highlight the recent advances and future perspectives in multicomponent-precipitation-strengthened alloys, including multicomponent steels, superalloys, and high-entropy alloys. The emphasis is placed on the unique microstructural features and challenges of multicomponent precipitation as well as their impacts on the strengthening behavior. Finally, future research areas for this class of materials are critically discussed.
Peltigera frigida Lichens and Their Substrates Reduce the Influence of Forest Cover Change on Phosphate Solubilizing Bacteria
Authors: Muster Cecilia , Leiva Diego , Morales Camila , Grafe Martin , Schloter Michael , Carú Margarita , Orlando Julieta
Published: June 2022

Phosphorus (P) is one of the most critical macronutrients in forest ecosystems. More than 70 years ago, some Chilean Patagonian temperate forests suffered wildfires and the subsequent afforestation with foreign tree species such as pines. Since soil P turnover is interlinked with the tree cover, this could influence soil P content and bioavailability. Next to soil microorganisms, which are key players in P transformation processes, a vital component of Patagonian temperate forest are lichens, which represent microbial hotspots for bacterial diversity. In the present study, we explored the impact of forest cover on the abundance of phosphate solubilizing bacteria (PSB) from three microenvironments of the forest floor: Peltigera frigida lichen thallus, their underlying substrates, and the forest soil without lichen cover. We expected that the abundance of PSB in the forest soil would be strongly affected by the tree cover composition since the aboveground vegetation influences the edaphic properties; but, as P. frigida has a specific bacterial community, lichens would mitigate this impact. Our study includes five sites representing a gradient in tree cover types, from a mature forest dominated by the native species Nothofagus pumilio, to native second-growth forests with a gradual increase in the presence of Pinus contorta in the last sites. In each site, we measured edaphic parameters, P fractions, and the bacterial potential to solubilize phosphate by quantifying five specific marker genes by qPCR. The results show higher soluble P, labile mineral P, and organic matter in the soils of the sites with a higher abundance of P. contorta, while most of the molecular markers were less abundant in the soils of these sites. Contrarily, the abundance of the molecular markers in lichens and substrates was less affected by the tree cover type. Therefore, the bacterial potential to solubilize phosphate is more affected by the edaphic factors and tree cover type in soils than in substrates and thalli of P. frigida lichens. Altogether, these results indicate that the microenvironments of lichens and their substrates could act as an environmental buffer reducing the influence of forest cover composition on bacteria involved in P turnover.
Mitochondrial Genome Contributes to the Thermal Adaptation of the Oomycete Phytophthora infestans
Authors: Shen Lin-Lin , Waheed Abdul , Wang Yan-Ping , Nkurikiyimfura Oswald , Wang Zong-Hua , Yang Li-Na , Zhan Jiasui
Published: June 2022

As a vital element of climate change, elevated temperatures resulting from global warming present new challenges to natural and agricultural sustainability, such as ecological disease management. Mitochondria regulate the energy production of cells in responding to environmental fluctuation, but studying their contribution to the thermal adaptation of species is limited. This knowledge is needed to predict future disease epidemiology for ecology conservation and food security. Spatial distributions of the mitochondrial genome (mtDNA) in 405 Phytophthora infestans isolates originating from 15 locations were characterized. The contribution of MtDNA to thermal adaptation was evaluated by comparative analysis of mtDNA frequency and intrinsic growth rate, relative population differentiation in nuclear and mtDNA, and associations of mtDNA distribution with local geography climate conditions. Significant variation in frequency, intrinsic growth rate, and spatial distribution was detected in mtDNA. Population differentiation in mtDNA was significantly higher than that in the nuclear genome, and spatial distribution of mtDNA was strongly associated with local climatic conditions and geographic parameters, particularly air temperature, suggesting natural selection caused by a local temperature is the main driver of the adaptation. Dominant mtDNA grew faster than the less frequent mtDNA. Our results provide useful insights into the evolution of pathogens under global warming. Given its important role in biological functions and adaptation to local air temperature, mtDNA intervention has become an increasing necessity for future disease management. To secure ecological integrity and food production under global warming, a synergistic study on the interactive effect of changing temperature on various components of biological and ecological functions of mitochondria in an evolutionary frame is urgently needed.
Combination of Isothermal Recombinase-Aided Amplification and CRISPR-Cas12a-Mediated Assay for Rapid Detection of Major Severe Acute Respiratory Syndrome Coronavirus 2 Variants of Concern
Authors: Lin Hongqing , Liang Yuanhao , Zou Lirong , Li Baisheng , Zhao Jianhui , Wang Haiying , Sun Jiufeng , Deng Xiaoling , Tang Shixing
Published: June 2022

Coronavirus disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 variants is a new and unsolved threat; therefore, it is an urgent and unmet need to develop a simple and rapid method for detecting and tracking SARS-CoV-2 variants. The spike gene of SARS-CoV-2 was amplified by isothermal recombinase-aided amplification (RAA) followed by the cleavage of CRISPR-Cas12a in which five allele-specific crRNAs and two Omicron-specific crRNAs were designed to detect and distinguish major SARS-CoV-2 variants of concerns (VOCs), including alpha, beta, delta variants, and Omicron sublineages BA.1 and BA.2. The whole reaction can be carried out in one tube at 39°C within 1.5–2 h, and the results can be read out by a fluorescence meter or naked eyes. Our results show that the RAA/CRISPR-Cas12a-based assay could readily distinguish the signature mutations, i.e., K417N, T478K, E484K, N501Y, and D614G, with a sensitivity of 100.0% and a specificity of 94.9–100.0%, respectively. The assay had a low limit of detection (LOD) of 104 copies/reaction and a concordance of 92.59% with Sanger sequencing results when detecting 54 SARS-CoV-2 positive clinical samples. The two Omicron-specific crRNAs can readily and correctly distinguish Omicron BA.1 and BA.2 sublineages with a LOD of as low as 20 copies/reaction. Furthermore, no cross-reaction was observed for all crRNAs analyzed when detecting clinical samples infected with 11 common respiratory pathogens. The combination of isothermal amplification and CRISPR-Cas12a-mediated assay is suitable for rapid detection of major SARS-CoV-2 variants in point-of-care testing and in resource-limiting settings. This simple assay could be quickly updated for emerging variants and implemented to routinely monitor and track the spread of SARS-CoV-2 variants.
In silico Analysis of Peptide-Based Biomarkers for the Diagnosis and Prevention of Latent Tuberculosis Infection
Authors: Cheng Peng , Wang Liang , Gong Wenping
Published: June 2022

Background

Latent tuberculosis infection (LTBI) is the primary source of active tuberculosis (ATB), but there are no specific methods for diagnosing and preventing LTBI.

Methods

Dominant T and B cell epitopes predicted from five antigens related to LTBI and Mycobacterium tuberculosis region of difference (LTBI-RD) were used to construct a novel polypeptide molecule (PPM). Then, the physicochemical properties, secondary structure, tertiary structure of the PPM, and its binding ability to toll-like receptor 2 (TLR2) and TLR4 were analyzed by bioinformatics tools. Finally, immune stimulation and expression optimization of the PPM were carried out.

Results

Four helper T lymphocytes (HTL) epitopes, five cytotoxic T lymphocytes (CTL) epitopes, and three B cell epitopes were predicted and screened from five LTBI-RD related antigens. These epitopes were connected in series with linkers and adjuvants to construct a novel PPM termed C543P. The results indicated that antigenicity and immunogenicity scores of the C543P candidate were 0.936399 and 1.36469, respectively. The structural analysis results showed that the C543P candidate had good stability. Its secondary structure contained 43.6% α-helix, the Z-score after tertiary structure optimization was −7.9, and the Ramachandran diagram showed that 88.77% amino acid residues of the C543P candidate were in the allowable region. Furthermore, the C543P candidate showed an excellent affinity to TLR2 (−1091.7kcal/mol) and TLR4 (−1102.7kcal/mol). In addition, we also analyzed the immunological characteristics of the C543P candidate. Immune stimulation prediction showed that the C543P candidate could effectively activate T and B lymphocytes and produce high levels of Th1 cytokines such as IFN-γ and IL-2.

Conclusion

We constructed a novel PPM with acceptable antigenicity, immunogenicity, stability, and ability to induce robust immune responses. This study provides a new diagnostic biomarker or peptides-based vaccine for LTBI diagnosis and prevention.
Mechanisms of Ferroptosis and Emerging Links to the Pathology of Neurodegenerative Diseases
Authors: Sun Yiyan , Xia Xiaohuan , Basnet Diksha , Zheng Jialin C. , Huang Jian , Liu Jianhui
Published: June 2022

Neurodegenerative diseases are a diverse class of diseases attributed to chronic progressive neuronal degeneration and synaptic loss in the brain and/or spinal cord, including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis and multiple sclerosis. The pathogenesis of neurodegenerative diseases is complex and diverse, often involving mitochondrial dysfunction, neuroinflammation, and epigenetic changes. However, the pathogenesis of neurodegenerative diseases has not been fully elucidated. Recently, accumulating evidence revealed that ferroptosis, a newly discovered iron-dependent and lipid peroxidation-driven type of programmed cell death, provides another explanation for the occurrence and progression of neurodegenerative diseases. Here, we provide an overview of the process and regulation mechanisms of ferroptosis, and summarize current research progresses that support the contribution of ferroptosis to the pathogenesis of neurodegenerative diseases. A comprehensive understanding of the emerging roles of ferroptosis in neurodegenerative diseases will shed light on the development of novel therapeutic technologies and strategies for slowing down the progression of these diseases.
Recent Advances in Nanomaterials for Diagnosis, Treatments, and Neurorestoration in Ischemic Stroke
Authors: Lin Xinru , Li Na , Tang Hongli
Published: June 2022

Stroke is a major public health issue, corresponding to the second cause of mortality and the first cause of severe disability. Ischemic stroke is the most common type of stroke, accounting for 87% of all strokes, where early detection and clinical intervention are well known to decrease its morbidity and mortality. However, the diagnosis of ischemic stroke has been limited to the late stages, and its therapeutic window is too narrow to provide rational and effective treatment. In addition, clinical thrombolytics suffer from a short half-life, inactivation, allergic reactions, and non-specific tissue targeting. Another problem is the limited ability of current neuroprotective agents to promote recovery of the ischemic brain tissue after stroke, which contributes to the progressive and irreversible nature of ischemic stroke and also the severity of the outcome. Fortunately, because of biomaterials’ inherent biochemical and biophysical properties, including biocompatibility, biodegradability, renewability, nontoxicity, long blood circulation time, and targeting ability. Utilization of them has been pursued as an innovative and promising strategy to tackle these challenges. In this review, special emphasis will be placed on the recent advances in the study of nanomaterials for the diagnosis and therapy of ischemic stroke. Meanwhile, nanomaterials provide much promise for neural tissue salvage and regeneration in brain ischemia, which is also highlighted.
Therapeutic Strategies and Metal-Induced Oxidative Stress: Application of Synchrotron Radiation Microbeam to Amyotrophic Lateral Sclerosis in the Kii Peninsula of Japan
Authors: Yoshida Sohei
Published: June 2022

A series of extensive gene-environment studies on amyotrophic lateral sclerosis (ALS) and Parkinsonism–dementia complex (PDC) in Guam Island, USA, and the Kii Peninsula of Japan, including Auyu Jakai, West New Guinea, have led us to hypothesize that a prolonged low calcium (Ca) and magnesium (Mg) intake, especially over generation, may cause oxidative stress to motor and nigral neurons by an increased uptake of environment metallic elements, i.e., aluminum (Al), manganese (Mn), and iron (Fe). Otherwise, 5–10% of total ALS cases are familial ALS (fALS), of which 20% of the fALS cases linked to a point mutation of Cu/Zn superoxide dismutase (SOD1). In the vicinity of the Kii Peninsula, about 7% of the ALS cases are also linked to the SOD1 mutation. Using synchrotron radiation (SR) microbeam, conglomerate inclusion (SOD1 aggregates) within a spinal motor neuron of the fALS case in the vicinity revealed a loss of copper (Cu) in contrast to extremely high contents of Zinc (Zn) and Ca. That means an exceptionally low Cu/Zn ratio with an increased Ca content, indicating the abnormalities of the active site of SOD1 protein of the fALS. Furthermore, sALS in the southernmost high incidence areas of the Kii Peninsula showed a low Cu/Zn ratio within a motor neuron, suggesting a fragility of SOD1 proteins. From the perspective of gene–environment interactions, the above two research trends may show a common oxidative stress underlying the neuronal degenerative process of ALS/PDC in the Kii Peninsula of Japan. Therefore, it is a crucial point for the prospect of therapeutic strategy to clarify a role of transition metals in the oxidative process in both ALS/PDC, including ALS elsewhere in the world. This paper reviews a history of the genetic epidemiological studies, especially from the aspect of gene–environment interaction, on ALS/PDC in the Kii and Guam high incidence foci and the results of a series of analytical research on trace metallic elements within neurons of both sALS and fALS cases, especially using a synchrotron radiation (SR) microbeam of Spring-8 and Photon Factory of Japan. The SR microbeam is an ideal X-ray source, which supplies an extremely high brilliance (high-intensity photon) and tunability (energy variability) to investigate trace metallic elements contained in biological specimens at the cellular level, even more without any damages. This research will provide a valuable information about the mechanism of oxidative stress involved in neuronal cell death in ALS and related neurodegenerative disorders. To elucidate the physicochemical mechanism of the oxidative process in neuronal degeneration, it will shed a new light on the therapeutic strategies for ALS/PDC in near future.
Neuroprotective Potential of Aromatic Herbs: Rosemary, Sage, and Lavender
Authors: Faridzadeh Arezoo , Salimi Yasaman , Ghasemirad Hamidreza , Kargar Meraj , Rashtchian Ava , Mahmoudvand Golnaz , Karimi Mohammad Amin , Zerangian Nasibeh , Jahani Negar , Masoudi Anahita , Sadeghian Dastjerdi Bahare , Salavatizadeh Marieh , Sadeghsalehi Hamidreza , Deravi Niloofar
Published: June 2022

Hundreds of millions of people around the world suffer from neurological disorders or have experienced them intermittently, which has significantly reduced their quality of life. The common treatments for neurological disorders are relatively expensive and may lead to a wide variety of side effects including sleep attacks, gastrointestinal side effects, blood pressure changes, etc. On the other hand, several herbal medications have attracted colossal popularity worldwide in the recent years due to their availability, affordable prices, and few side effects. Aromatic plants, sage (Salvia officinalis), lavender (Lavandula angustifolia), and rosemary (Salvia Rosmarinus) have already shown anxiolytics, anti-inflammatory, antioxidant, and neuroprotective effects. They have also shown potential in treating common neurological disorders, including Alzheimer's disease, Parkinson's disease, migraine, and cognitive disorders. This review summarizes the data on the neuroprotective potential of aromatic herbs, sage, lavender, and rosemary.
Marketing of Food and Beverages to Children in the Eastern Mediterranean Region: A Situational Analysis of the Regulatory Framework
Authors: Al-Jawaldeh Ayoub , Jabbour Jana
Published: June 2022

Marketing of food items high in added saturated and/or trans-fat, sugar, or sodium (HFSS) negatively affect consumption patterns of young children. The World Health Organization (WHO) advised countries to regulate the marketing of foods and non-alcoholic beverages to young populations. The aim of this manuscript is to provide a situational analysis of the regulatory framework of food marketing policies targeting children in the Eastern Mediterranean Region (EMR). A semi structured questionnaire was shared with the focal points of EMR member states inquiring about the reforms and monitoring initiatives in place. Electronic databases were searched for relevant publications between 2005 and 2021. Results revealed that even though 68% of countries discussed the recommendations, progress toward the WHO set goals has been slow with only 14% of countries implementing any kind of restrictions and none executing a comprehensive approach. Reforms have focused on local television and radio marketing and left out several loopholes related to marketing on the internet, mobile applications, and cross border marketing. Recent monitoring initiatives revealed a slight improvement in the content of advertised material. Yet, unhealthy products are the most promoted in the region. This review identified the need to intensify the efforts to legislate comprehensive food marketing policies within and across EMR countries.
Molecular Characterization of the Tumor Microenvironment in Renal Medullary Carcinoma
Authors: Tourigny David S. , Zucker Mark , Kim Minsoo , Russo Paul , Coleman Jonathan , Lee Chung-Han , Carlo Maria I. , Chen Ying-Bei , Hakimi A. Ari , Kotecha Ritesh R. , Reznik Ed
Published: June 2022

Renal medullary carcinoma (RMC) is a highly aggressive disease associated with sickle hemoglobinopathies and universal loss of the tumor suppressor gene SMARCB1. RMC has a relatively low rate of incidence compared with other renal cell carcinomas (RCCs) that has hitherto made molecular profiling difficult. To probe this rare disease in detail we performed an in-depth characterization of the RMC tumor microenvironment using a combination of genomic, metabolic and single-cell RNA-sequencing experiments on tissue from a representative untreated RMC patient, complemented by retrospective analyses of archival tissue and existing published data. Our study of the tumor identifies a heterogenous population of malignant cell states originating from the thick ascending limb of the Loop of Henle within the renal medulla. Transformed RMC cells displayed the hallmarks of increased resistance to cell death by ferroptosis and proteotoxic stress driven by MYC-induced proliferative signals. Specifically, genomic characterization of RMC tumors provides substantiating evidence for the recently proposed dependence of SMARCB1-difficient cancers on proteostasis modulated by an intact CDKN2A-p53 pathway. We also provide evidence that increased cystine-mTORC-GPX4 signaling plays a role in protecting transformed RMC cells against ferroptosis. We further propose that RMC has an immune landscape comparable to that of untreated RCCs, including heterogenous expression of the immune ligand CD70 within a sub-population of tumor cells. The latter could provide an immune-modulatory role that serves as a viable candidate for therapeutic targeting.
Problems in CSF and Ophthalmic Disease Research
Authors: Machiele Ryan , Frankfort Benjamin Jay , Killer Hanspeter Esriel , Fleischman David
Published: June 2022

There has been significant interest and progress in the understanding of cerebrospinal fluid pressure and its relationship to glaucoma and other ophthalmic diseases. However, just as every physiologic fluid pressure fluctuates, cerebrospinal fluid pressure (CSFP) is similarly dynamic. Coupling this with the difficulty in measuring the pressure, there are many obstacles in furthering this field of study. This review highlights some of the difficulties in CSFP research, including fluid compartmentalization, estimation equations, and pressure fluctuation. Keeping these limitations in mind will hopefully improve the quality and context of this burgeoning field.