bluuebunny/crossref_metadata_2025 huggingface dataset:
Security and Violence Perception of Medical Interns during Social Service Practice in Mexico
Authors: Martinez-Fierro Margarita L. , Ramirez-Madrigal Miguel A. , Covarrubias-Carrillo Rosa Martha , Avila-Carrasco Lorena , Flores-Morales Virginia , Meza-Zavala Oscar G. , de León-Sigg María , Vázquez-Reyes Sodel , Mauricio-González Alejandro , Velasco-Elizondo Perla , Garza-Veloz Idalia
Published: December 2021

The increase of insecurity levels in Mexico, as well as the fact that violence is a frequent experience among health personnel, motivated this study whose purpose was to evaluate the perception of security and violence that social service medical interns (SSMI) had on the institutions and localities where they carried out their social work and make visible the main types of violence to which they were exposed. This was a cross-sectional study, based on a perception survey self-administered to 157 SSMI from Zacatecas, in Mexico. A high proportion of the participants (75.8%) stated that they were victims of violence, describing 134 incidents; however, only 33.6% of SSMI made an official report. The reported incidents were related to organized crime (31.9%), verbal violence (20.6%), violence by the authorities (14.7%) and sexual harassment (11.8%). One hundred percent of the victims of sexual harassment were women (p = 0.039). According to the above, it is a priority to generate strategies to prevent and reduce the risk of exposure to the violence generated in the medical units and communities where SSMI carry out their activities as medical graduates, as well as, to efficiently process formal violence reports to promote a safe environment that favors the fulfillment of the practice of SSMIs in Mexico.
Help-Seeking as a Maladaptive Coping Style in the Pandemic Scenario: What Worked and What Did Not for Facing This New Stressor
Authors: Simione Luca , Gnagnarella Camilla , Spina Giulia , Bersani Giuseppe
Published: December 2021

The spread of COVID-19 and its related confinement measures were important stressors for a large part of the global population, with massive effects on both physical and mental health. Assessing how individuals coped with such a stressor and which strategies were effective is one of the main challenges for psychological research. In this study, we aimed to investigate the coping strategies implied during the COVID-19 lockdown and their effectiveness. We recruited 374 Italian participants through convenience sampling during the first pandemic wave (April 2020). We administered to our participants an online battery of questionnaires including the Brief COPE, the use of alternative coping strategies proposed by the WHO to help people facing lockdown stress, and a range of psychological symptoms. An exploratory factor analysis conducted on the subscales of the Brief COPE revealed a three-factor structure. Following the previous literature, we named these factors engagement, disengagement, and help-seeking coping styles. In the pandemic scenario, the engagement and disengagement styles revealed the typical correlation patterns with psychological symptoms (i.e., the engagement was adaptive while the disengagement was maladaptive). Instead, contrary to previous literature, help-seeking was positively related to psychological symptoms, suggesting a mismatch between searching for help and finding it during the lockdown. This result supports the importance of evaluating the effectiveness of coping strategies in the pandemic scenario, to give more compelling and precise advice to the population.
A Multiscale Land Use Regression Approach for Estimating Intraurban Spatial Variability of PM2.5 Concentration by Integrating Multisource Datasets
Authors: Shi Yuan , Lau Alexis Kai-Hon , Ng Edward , Ho Hung-Chak , Bilal Muhammad
Published: December 2021

Poor air quality has been a major urban environmental issue in large high-density cities all over the world, and particularly in Asia, where the multiscale complex of pollution dispersal creates a high-level spatial variability of exposure level. Investigating such multiscale complexity and fine-scale spatial variability is challenging. In this study, we aim to tackle the challenge by focusing on PM2.5 (particulate matter with an aerodynamic diameter less than 2.5 µm,) which is one of the most concerning air pollutants. We use the widely adopted land use regression (LUR) modeling technique as the fundamental method to integrate air quality data, satellite data, meteorological data, and spatial data from multiple sources. Unlike most LUR and Aerosol Optical Depth (AOD)-PM2.5 studies, the modeling process was conducted independently at city and neighborhood scales. Correspondingly, predictor variables at the two scales were treated separately. At the city scale, the model developed in the present study obtains better prediction performance in the AOD-PM2.5 relationship when compared with previous studies (R2¯ from 0.72 to 0.80). At the neighborhood scale, point-based building morphological indices and road network centrality metrics were found to be fit-for-purpose indicators of PM2.5 spatial estimation. The resultant PM2.5 map was produced by combining the models from the two scales, which offers a geospatial estimation of small-scale intraurban variability.
Does Industrial Transfer Change the Spatial Structure of CO2 Emissions?—Evidence from Beijing-Tianjin-Hebei Region in China
Authors: Yue Jiachen , Zhu Huasheng , Yao Fei
Published: December 2021

As an important cause of global warming, CO2 emissions have become a research hotspot in recent years. Industrial transfer impacts regional CO2 emissions and is related to the low-carbon development of regional industries. Taking the Beijing-Tianjin-Hebei region (BTH region) as an example, this study analysed industrial transfer’s direct and indirect impacts on CO2 emissions based on a mediating model and two-way fixed effect panel regression. The results obtained indicate that industrial transfer-in has promoted CO2 emissions to a small extent, and the positive impact of industrial transfer-in on CO2 emissions wanes over time. Industrial transfer affects CO2 emissions by acting on the economic level, on population size, and on urbanisation level, but the indirect effect is weaker than the direct effect. Industrial transfer does not lead to technological upgrading, but the latter is an effective means of carbon emission reduction. Industrial transfer-in has shown a positive effect on CO2 emissions for most cities, but there are exceptions, such as Cangzhou. In the future, the BTH region should maintain coordinated development among cities and improve the cooperative innovation mechanism for energy conservation and emission reduction.
Attitudes towards Mandatory Occupational Vaccination and Intention to Get COVID-19 Vaccine during the First Pandemic Wave among Mongolian Healthcare Workers: A Cross-Sectional Survey
Authors: Turbat Battsetseg , Sharavyn Bold , Tsai Feng-Jen
Published: December 2021

Mandatory occupational vaccination for health care workers (HCWs) is a debatable issue, especially during the COVID-19 pandemic. This study aimed to determine Mongolian HCWs’ attitudes towards mandatory occupational vaccination, the intention to get the COVID-19 vaccine, and the associated factors. A cross-sectional study based on an online survey with a convenience sampling strategy was conducted from February to April 2021 among 238 Mongolia HCWs. Chi-square and logistic regression were performed for analysis. While only 39.9% of HCWs were aware of recommended occupational vaccinations, they highly agreed with the mandatory occupational vaccination on HCWs (93.7%). The agreement rate is significantly higher than their attitude toward general vaccination (93.7% vs. 77.8%). HCW’s willingness to get the COVID-19 vaccine was high (67.2%). HCWs aged 26–35 years old who worked in tertiary level hospitals had less willingness to get the COVID-19 vaccine (50%). Participants with lower confidence in the efficacy of the COVID-19 vaccine (ORs = 15.659) and less positive attitudes toward general vaccination (ORs = 5.288) were less likely to get the COVID-19 vaccine. Mongolian HCWs’ agreement rate of mandatory occupational vaccination is higher than other countries. Their intention to get the COVID-19 vaccine is high and associated with confidence in the effectiveness of the vaccine.
Associations between Melatonin, Neuroinflammation, and Brain Alterations in Depression
Authors: Won Eunsoo , Na Kyoung-Sae , Kim Yong-Ku
Published: December 2021

Pro-inflammatory systemic conditions that can cause neuroinflammation and subsequent alterations in brain regions involved in emotional regulation have been suggested as an underlying mechanism for the pathophysiology of major depressive disorder (MDD). A prominent feature of MDD is disruption of circadian rhythms, of which melatonin is considered a key moderator, and alterations in the melatonin system have been implicated in MDD. Melatonin is involved in immune system regulation and has been shown to possess anti-inflammatory properties in inflammatory conditions, through both immunological and non-immunological actions. Melatonin has been suggested as a highly cytoprotective and neuroprotective substance and shown to stimulate all stages of neuroplasticity in animal models. The ability of melatonin to suppress inflammatory responses through immunological and non-immunological actions, thus influencing neuroinflammation and neurotoxicity, along with subsequent alterations in brain regions that are implicated in depression, can be demonstrated by the antidepressant-like effects of melatonin. Further studies that investigate the associations between melatonin, immune markers, and alterations in the brain structure and function in patients with depression could identify potential MDD biomarkers.
Role of Biomarkers as Prognostic Factors in Acute Peripheral Facial Palsy
Authors: Kim Tae Hoon , Yeo Seung Geun , Byun Jae Yong
Published: December 2021

Acute peripheral facial palsy (APFP), including Bell’s palsy and Ramsay Hunt syndrome, is a disease that affects daily life through facial motor dysfunction, causing psychological problems. Various tests to evaluate prognosis have been studied; however, there are no validated predictive biomarkers to guide clinical decision making. Therefore, specific biomarkers that respond to treatment are required to understand prognostic outcomes. In this review, we discuss existing literature regarding the role of APFP biomarkers in prognosis and recovery. We searched the PubMed, EMBASE, and Cochrane Library databases for relevant papers. Our screening identified relevant studies and biomarkers correlating with the identification of predictive biomarkers. Only studies published between January 2000 and October 2021 were included. Our search identified 5835 abstracts, of which 35 were selected. All biomarker samples were obtained from blood and were used in the evaluation of disease severity and prognosis associated with recovery. These biomarkers have been effective prognostic or predictive factors under various conditions. Finally, we classified them into five categories. There is no consensus in the literature on the correlation between outcomes and prognostic factors for APFP. Furthermore, the correlation between hematologic laboratory values and APFP prognosis remains unclear. However, it is important to identify new methods for improving the accuracy of facial paralysis prognosis prediction. Therefore, we systematically evaluated prognostic and potentially predictive APFP biomarkers. Unfortunately, a predictive biomarker validating APFP prognosis remains unknown. More prospective studies are required to reveal and identify promising biomarkers providing accurate prognosis.
Structural and Functional Change in Albino Rat Retina Induced by Various Visible Light Wavelengths
Authors: Kaidzu Sachiko , Okuno Tsutomu , Tanito Masaki , Ohira Akihiro
Published: December 2021

The effects of visible light, from short to long wavelengths, on the retina were investigated functionally and histologically. The left eyes of Sprague–Dawley albino rats (6-weeks old, n = 6 for each wavelength) were exposed to seven narrow-band wavelengths (central wavelengths, 421, 441, 459, 501, 541, 581, and 615 nm) with bandwidths of 16 to 29 nm (half bandwidth, ±8–14.5 nm) using a xenon lamp source with bandpass filters at the retinal radiant exposures of 340 and 680 J/cm2. The right unexposed eyes served as controls. Seven days after exposure, flash electroretinograms (ERGs) were recorded, and the outer nuclear layer (ONL) thickness was measured. Compared to the unexposed eyes, significant reductions in the a- and b-wave ERG amplitudes were seen in eyes exposed to 460-nm or shorter wavelengths of light. The ONL thickness near the optic nerve head also tended to decrease with exposure to shorter wavelengths. The decreased ERG amplitudes and ONL thicknesses were most prominent in eyes exposed to 420-nm light at both radiant exposures. When the wavelengths were the same, the higher the amount of radiant exposure and the stronger the damage. Compared to the unexposed eyes, the a- and b-waves did not decrease significantly in eyes exposed to 500-nm or longer wavelength light. The results indicate that the retinal damage induced by visible light observed in albino rats depends on the wavelength and energy level of the exposed light.
Combination of Genomic and Transcriptomic Approaches Highlights Vascular and Circadian Clock Components in Multiple Sclerosis
Authors: Scapoli Chiara , Ziliotto Nicole , Lunghi Barbara , Menegatti Erica , Salvi Fabrizio , Zamboni Paolo , Baroni Marcello , Mascoli Francesco , Bernardi Francesco , Marchetti Giovanna
Published: December 2021

Aiming at exploring vascular components in multiple sclerosis (MS) with brain outflow disturbance, we combined transcriptome analysis in MS internal jugular vein (IJV) wall with WES in MS families with vertical transmission of disease. Main results were the differential expression in IJV wall of 16 MS-GWAS genes and of seven genes (GRIN2A, GRIN2B, IL20RB, IL26, PER3, PITX2, and PPARGC1A) not previously indicated by GWAS but encoding for proteins functionally interacting with MS candidate gene products. Strikingly, 22/23 genes have been previously associated with vascular or neuronal traits/diseases, nine encoded for transcriptional factors/regulators and six (CAMK2G, GRIN2A, GRIN2B, N1RD1, PER3, PPARGC1A) for circadian entrainment/rhythm components. Among the WES low-frequency (MAF ≤ 0.04) SNPs (n = 7) filtered in the 16 genes, the NR1D1 rs17616365 showed significantly different MAF in the Network for Italian Genomes affected cohort than in the 1000 Genome Project Tuscany samples. This pattern was also detected in five nonintronic variants (GRIN2B rs1805482, PER3 rs2640909, PPARGC1A rs2970847, rs8192678, and rs3755863) in genes coding for functional partners. Overall, the study proposes specific markers and low-frequency variants that might help (i) to understand perturbed biological processes in vascular tissues contributing to MS disease, and (ii) to characterize MS susceptibility genes for functional association with disease-pathways.
E2f2 Attenuates Apoptosis of Activated T Lymphocytes and Protects from Immune-Mediated Injury through Repression of Fas and FasL
Authors: Mustafa Noor , Mitxelena Jone , Infante Arantza , Zenarruzabeitia Olatz , Eriz Ainhoa , Iglesias-Ara Ainhoa , Zubiaga Ana M.
Published: December 2021

Targeted disruption of E2f2 in mice causes T-cell hyperactivation and a disproportionate cell cycle entry upon stimulation. However, E2f2−/− mice do not develop a lymphoproliferative condition. We report that E2f2 plays a Fas-dependent anti-apoptotic function in vitro and in vivo. TCR-stimulated murine E2f2−/− T cells overexpress the proapoptotic genes Fas and FasL and exhibit enhanced apoptosis, which is prevented by treatment with neutralizing anti-FasL antibodies. p53 pathway is activated in TCR-stimulated E2f2−/− lymphocytes, but targeted disruption of p53 in E2f2−/− mice does not abrogate Fas/FasL expression or apoptosis, implying a p53-independent apoptotic mechanism. We show that E2f2 is recruited to Fas and FasL gene promoters to repress their expression. in vivo, E2f2−/− mice are prone to develop immune-mediated liver injury owing to an aberrant lymphoid Fas/FasL activation. Taken together, our results suggest that E2f2-dependent inhibition of Fas/FasL pathway may play a direct role in limiting the development of immune-mediated pathologies.
Physical Considerations for In Vitro ESWT Research Design
Authors: Slezak Cyrill , Rose Roland , Jilge Julia M. , Nuster Robert , Hercher David , Slezak Paul
Published: December 2021

In vitro investigations, which comprise the bulk of research efforts geared at identifying an underlying biomechanical mechanism for extracorporeal shock wave therapy (ESWT), are commonly hampered by inadequate descriptions of the underlying therapeutic acoustical pressure waves. We demonstrate the necessity of in-situ sound pressure measurements inside the treated samples considering the significant differences associated with available applicator technologies and cell containment. A statistical analysis of pulse-to-pulse variability in an electrohydraulic applicator yields a recommendation for a minimal pulse number of n = 300 for cell pallets and suspensions to achieve reproducible treatments. Non-linear absorption behavior of sample holders and boundary effects are shown for transient peak pressures and applied energies and may serve as a guide when in-situ measurements are not available or can be used as a controllable experimental design factor. For the use in microbiological investigations of ESWT we provide actionable identification of common problems in describing physical shockwave parameters and improving experimental setups by; (1) promoting in-situ sound field measurements, (2) statistical evaluation of applicator variability, and (3) extrapolation of treatment parameters based on focal and treatment volumes.
Availability of Arg, but Not tRNA, Is a Rate-Limiting Factor for Intracellular Arginylation
Authors: Avcilar-Kucukgoze Irem , MacTaggart Brittany , Kashina Anna
Published: December 2021

Protein arginylation, mediated by arginyltransferase ATE1, is a posttranslational modification of emerging biological importance that consists of transfer of the amino acid Arg from tRNA to protein and peptide targets. ATE1 can bind tRNA and exhibits specificity toward particular tRNA types, but its dependence on the availability of the major components of the arginylation reaction has never been explored. Here we investigated key intracellular factors that can potentially regulate arginylation in vivo, including several tRNA types that show strong binding to ATE1, as well as availability of free Arg, in an attempt to identify intracellular rate limiting steps for this enzyme. Our results demonstrate that, while modulation of tRNA levels in cells does not lead to any changes in intracellular arginylation efficiency, availability of free Arg is a potentially rate-limiting factor that facilitates arginylation if added to the cultured cells. Our results broadly outline global pathways that may be involved in the regulation of arginylation in vivo.
Revising the Role of Cortical Cytoskeleton during Secretion: Actin and Myosin XI Function in Vesicle Tethering
Authors: Zhang Weiwei , Staiger Christopher J.
Published: December 2021

In plants, secretion of cell wall components and membrane proteins plays a fundamental role in growth and development as well as survival in diverse environments. Exocytosis, as the last step of the secretory trafficking pathway, is a highly ordered and precisely controlled process involving tethering, docking, and fusion of vesicles at the plasma membrane (PM) for cargo delivery. Although the exocytic process and machinery are well characterized in yeast and animal models, the molecular players and specific molecular events that underpin late stages of exocytosis in plant cells remain largely unknown. Here, by using the delivery of functional, fluorescent-tagged cellulose synthase (CESA) complexes (CSCs) to the PM as a model system for secretion, as well as single-particle tracking in living cells, we describe a quantitative approach for measuring the frequency of vesicle tethering events. Genetic and pharmacological inhibition of cytoskeletal function, reveal that the initial vesicle tethering step of exocytosis is dependent on actin and myosin XI. In contrast, treatments with the microtubule inhibitor, oryzalin, did not significantly affect vesicle tethering or fusion during CSC exocytosis but caused a minor increase in transient or aborted tethering events. With data from this new quantitative approach and improved spatiotemporal resolution of single particle events during secretion, we generate a revised model for the role of the cortical cytoskeleton in CSC trafficking.
Composites Based on Gellan Gum, Alginate and Nisin-Enriched Lipid Nanoparticles for the Treatment of Infected Wounds
Authors: Reczyńska-Kolman Katarzyna , Hartman Kinga , Kwiecień Konrad , Brzychczy-Włoch Monika , Pamuła Elżbieta
Published: December 2021

Due to growing antimicrobial resistance to antibiotics, novel methods of treatment of infected wounds are being searched for. The aim of this research was to develop a composite wound dressing based on natural polysaccharides, i.e., gellan gum (GG) and a mixture of GG and alginate (GG/Alg), containing lipid nanoparticles loaded with antibacterial peptide—nisin (NSN). NSN-loaded stearic acid-based nanoparticles (NP_NSN) were spherical with an average particle size of around 300 nm and were cytocompatible with L929 fibroblasts for up to 500 µg/mL. GG and GG/Alg sponges containing either free NSN (GG + NSN and GG/Alg + NSN) or NP_NSN (GG + NP_NSN and GG/Alg + NP_NSN) were highly porous with a high swelling capacity (swelling ratio above 2000%). Encapsulation of NSN within lipid nanoparticles significantly slowed down NSN release from GG-based samples for up to 24 h (as compared to GG + NSN). The most effective antimicrobial activity against Gram-positive Streptococcus pyogenes was observed for GG + NP_NSN, while in GG/Alg it was decreased by interactions between NSN and Alg, leading to NSN retention within the hydrogel matrix. All materials, except GG/Alg + NP_NSN, were cytocompatible with L929 fibroblasts and did not cause an observable delay in wound healing. We believe that the developed materials are promising for wound healing application and the treatment of bacterial infections in wounds.
Berberine Decreases Intestinal GLUT2 Translocation and Reduces Intestinal Glucose Absorption in Mice
Authors: Zhang Min , Yang Hongyan , Yang Erwan , Li Jia , Dong Ling
Published: December 2021

Postprandial hyperglycemia is an important causative factor of type 2 diabetes mellitus, and permanent localization of intestinal GLUT2 in the brush border membrane is an important reason of postprandial hyperglycemia. Berberine, a small molecule derived from Coptidis rhizome, has been found to be potent at lowering blood glucose, but how berberine lowers postprandial blood glucose is still elusive. Here, we investigated the effect of berberine on intestinal glucose transporter 2 (GLUT2) translocation and intestinal glucose absorption in type 2 diabetes mouse model. Type 2 diabetes was induced by feeding of a high-fat diet and injection of streptozotocin and diabetic mice were treated with berberine for 6 weeks. The effects of berberine on intestinal glucose transport and GLUT2 translocation were accessed in isolated intestines and intestinal epithelial cells (IEC-6), respectively. We found that berberine treatment improved glucose tolerance and systemic insulin sensitivity in diabetic mice. Furthermore, berberine decreased intestinal glucose transport and inhibited GLUT2 translocation from cytoplasm to brush border membrane in intestinal epithelial cells. Mechanistically, berberine inhibited intestinal insulin-like growth factor 1 (IGF-1R) phosphorylation and thus reduced localization of PLC-β2 in the membrane, leading to decreased GLUT2 translocation. These results suggest that berberine reduces intestinal glucose absorption through inhibiting IGF-1R-PLC-β2-GLUT2 signal pathway.
Single-Chain Fragment Variables Targeting Leukocidin ED Can Alleviate the Inflammation of Staphylococcus aureus-Induced Mastitis in Mice
Authors: Zhang Lei , Ye Xin , Jia Yan , Cheng Manling , Wu Dangjin , Tohti Kalbinur , Zhu Jianguo
Published: December 2021

Staphylococcus aureus is a vital bovine mastitis pathogen causing huge economic losses to the dairy industry worldwide. In our previous studies, leukotoxin ED (LukED) was detected in most S. aureus strains isolated from bovine mastitis. Here, four single-chain fragment variables (scFvs) (ZL8 and ZL42 targeting LukE, ZL22 and ZL23 targeting LukD) were obtained using purified LukE and LukD proteins as the antigens after five rounds of bio-panning. The complementarity-determining region 3 (CDR3) of the VH domain of these scFvs exhibited significant diversities. In vitro, the scFvs significantly decreased LukED-induced cell killing by inhibiting the binding of LukED to chemokine receptors (CCR5 and CXCR2) and reduced the death rates of bovine neutrophils and MAC-T cells caused by LukED and S. aureus (p < 0.05). In an S. aureus-induced mouse mastitis model, histopathology and MPO results revealed that scFvs ameliorated the histopathological damages and reduced the infiltration of inflammatory cells (p < 0.05). The ELISA and qPCR assays showed that scFvs reduced the transcription and expression levels of Tumor Necrosis Factor-alpha (TNF-α), interleukin-1β (IL-1β), IL-6, IL-8 and IL-18 (p < 0.05). The overall results demonstrated the protective anti-inflammatory effect of scFvs in vitro and in vivo, enlightening the potential role of scFvs in the prevention and treatment of S. aureus-induced mastitis.
Immunopathological Analysis of a Mouse Model of Arthritis-Associated Scleritis and Implications for Molecular Targeted Therapy for Severe Scleritis
Authors: Nishio Yusuke , Taniguchi Hiroko , Takeda Ayaka , Hori Junko
Published: December 2021

Scleritis involves inflammation of the sclera, which constitutes 75% of the wall of the eye. This pathology is often seen as an ocular lesion associated with systemic inflammatory diseases. Severe types of scleritis such as posterior scleritis require urgent immunosuppressive treatments, including molecularly targeted therapies to avoid permanent visual impairment. Which molecules should be selected as targets has remained unclear. To clarify the pathogenesis of scleritis and propose appropriate target molecules for therapy, we have established novel animal model of scleritis by modifying the Collagen-II Induced Arthritis (CIA) model. Immunization twice with collagen II emulsified with complete Freund’s adjuvant (CFA) caused arthritis and scleritis. The clinical appearance resembled human diffuse scleritis. Histopathological analysis suggested that macrophages, plasma cells, deposition of immune complexes, and growth of blood and lymphatic vessels are involved in the pathogenesis of CIA-associated scleritis. In addition, we analysed the background diseases of posterior scleritis and responses to molecularly targeted therapies as a case series study. We inferred from both the animal model and case series study that targets should not be T cells, but factors inhibiting macrophage activity such as tumor necrosis factor (TNF) and interleukin (IL)-6, and molecules suppressing antibody-producing cells such as CD20 on B cells should be targeted by molecularly targeted therapies.
Brassinosteroids and the Tolerance of Cereals to Low and High Temperature Stress: Photosynthesis and the Physicochemical Properties of Cell Membranes
Authors: Sadura Iwona , Janeczko Anna
Published: December 2021

Cereals, which belong to the Poaceae family, are the most economically important group of plants. Among abiotic stresses, temperature stresses are a serious and at the same time unpredictable problem for plant production. Both frost (in the case of winter cereals) and high temperatures in summer (especially combined with a water deficit in the soil) can result in significant yield losses. Plants have developed various adaptive mechanisms that have enabled them to survive periods of extreme temperatures. The processes of acclimation to low and high temperatures are controlled, among others, by phytohormones. The current review is devoted to the role of brassinosteroids (BR) in cereal acclimation to temperature stress with special attention being paid to the impact of BR on photosynthesis and the membrane properties. In cereals, the exogenous application of BR increases frost tolerance (winter rye, winter wheat), tolerance to cold (maize) and tolerance to a high temperature (rice). Disturbances in BR biosynthesis and signaling are accompanied by a decrease in frost tolerance but unexpectedly an improvement of tolerance to high temperature (barley). BR exogenous treatment increases the efficiency of the photosynthetic light reactions under various temperature conditions (winter rye, barley, rice), but interestingly, BR mutants with disturbances in BR biosynthesis are also characterized by an increased efficiency of PSII (barley). BR regulate the sugar metabolism including an increase in the sugar content, which is of key importance for acclimation, especially to low temperatures (winter rye, barley, maize). BR either participate in the temperature-dependent regulation of fatty acid biosynthesis or control the processes that are responsible for the transport or incorporation of the fatty acids into the membranes, which influences membrane fluidity (and subsequently the tolerance to high/low temperatures) (barley). BR may be one of the players, along with gibberellins or ABA, in acquiring tolerance to temperature stress in cereals (particularly important for the acclimation of cereals to low temperature).
Roles and Mechanisms of the Protein Quality Control System in Alzheimer’s Disease
Authors: Liu Yaping , Ding Runrong , Xu Ze , Xue Yuan , Zhang Dongdong , Zhang Yujing , Li Wenjie , Li Xing
Published: December 2021

Alzheimer’s disease (AD) is characterized by the deposition of senile plaques (SPs) and the formation of neurofibrillary tangles (NTFs), as well as neuronal dysfunctions in the brain, but in fact, patients have shown a sustained disease progression for at least 10 to 15 years before these pathologic biomarkers can be detected. Consequently, as the most common chronic neurological disease in the elderly, the challenge of AD treatment is that it is short of effective biomarkers for early diagnosis. The protein quality control system is a collection of cellular pathways that can recognize damaged proteins and thereby modulate their turnover. Abundant evidence indicates that the accumulation of abnormal proteins in AD is closely related to the dysfunction of the protein quality control system. In particular, it is the synthesis, degradation, and removal of essential biological components that have already changed in the early stage of AD, which further encourages us to pay more attention to the protein quality control system. The review mainly focuses on the endoplasmic reticulum system (ERS), autophagy–lysosome system (ALS) and the ubiquitin–proteasome system (UPS), and deeply discusses the relationship between the protein quality control system and the abnormal proteins of AD, which can not only help us to understand how and why the complex regulatory system becomes malfunctional during AD progression, but also provide more novel therapeutic strategies to prevent the development of AD.
Glial Cell Activation and Oxidative Stress in Retinal Degeneration Induced by β-Alanine Caused Taurine Depletion and Light Exposure
Authors: Martínez-Vacas Ana , Di Pierdomenico Johnny , Valiente-Soriano Francisco J. , Vidal-Sanz Manuel , Picaud Serge , Villegas-Pérez María Paz , García-Ayuso Diego
Published: December 2021

We investigate glial cell activation and oxidative stress induced by taurine deficiency secondary to β-alanine administration and light exposure. Two months old Sprague-Dawley rats were divided into a control group and three experimental groups that were treated with 3% β-alanine in drinking water (taurine depleted) for two months, light exposed or both. Retinal and external thickness were measured in vivo at baseline and pre-processing with Spectral-Domain Optical Coherence Tomography (SD-OCT). Retinal cryostat cross sections were immunodetected with antibodies against various antigens to investigate microglial and macroglial cell reaction, photoreceptor outer segments, synaptic connections and oxidative stress. Taurine depletion caused a decrease in retinal thickness, shortening of photoreceptor outer segments, microglial cell activation, oxidative stress in the outer and inner nuclear layers and the ganglion cell layer and synaptic loss. These events were also observed in light exposed animals, which in addition showed photoreceptor death and macroglial cell reactivity. Light exposure under taurine depletion further increased glial cell reaction and oxidative stress. Finally, the retinal pigment epithelial cells were Fluorogold labeled and whole mounted, and we document that taurine depletion impairs their phagocytic capacity. We conclude that taurine depletion causes cell damage to various retinal layers including retinal pigment epithelial cells, photoreceptors and retinal ganglion cells, and increases the susceptibility of the photoreceptor outer segments to light damage. Thus, beta-alanine supplements should be used with caution.
Homologous Recombination Deficiencies and Hereditary Tumors
Authors: Yamamoto Hideki , Hirasawa Akira
Published: December 2021

Homologous recombination (HR) is a vital process for repairing DNA double-strand breaks. Germline variants in the HR pathway, comprising at least 10 genes, such as BRCA1, BRCA2, ATM, BARD1, BRIP1, CHEK2, NBS1(NBN), PALB2, RAD51C, and RAD51D, lead to inherited susceptibility to specific types of cancers, including those of the breast, ovaries, prostate, and pancreas. The penetrance of germline pathogenic variants of each gene varies, whereas all their associated protein products are indispensable for maintaining a high-fidelity DNA repair system by HR. The present review summarizes the basic molecular mechanisms and components that collectively play a role in maintaining genomic integrity against DNA double-strand damage and their clinical implications on each type of hereditary tumor.
Optimal Efficacy and Safety of Humanized Anti-Scg3 Antibody to Alleviate Oxygen-Induced Retinopathy
Authors: He Ye , Tian Hong , Dai Chang , Wen Rong , Li Xiaorong , Webster Keith A. , Li Wei
Published: December 2021

The retinopathy of prematurity (ROP), a neovascular retinal disorder presenting in premature infants, is the leading causes of blindness in children. Currently, there is no approved drug therapy for ROP in the U.S., highlighting the urgent unmet clinical need for a novel therapeutic to treat the disease. Secretogranin III (Scg3) was recently identified as a disease-selective angiogenic factor, and Scg3-neutralizing monoclonal antibodies were reported to alleviate pathological retinal neovascularization in mouse models. In this study, we characterized the efficacy and safety of a full-length humanized anti-Scg3 antibody (hAb) to ameliorate retinal pathology in oxygen-induced retinopathy (OIR) mice, a surrogate model of ROP, by implementing histological and functional analyses. Our results demonstrate that the anti-Scg3 hAb outperforms the vascular endothelial growth factor inhibitor aflibercept in terms of efficacy and safety to treat OIR mice. Our findings support the development of anti-Scg3 hAb for clinical application.
Impact of High-Dose Irradiation on Human iPSC-Derived Cardiomyocytes Using Multi-Electrode Arrays: Implications for the Antiarrhythmic Effects of Cardiac Radioablation
Authors: Kim Jae Sik , Choi Seong Woo , Park Yun-Gwi , Kim Sung Joon , Choi Chang Heon , Cha Myung-Jin , Chang Ji Hyun
Published: December 2021

Cardiac radioablation is emerging as an alternative option for refractory ventricular arrhythmias. However, the immediate acute effect of high-dose irradiation on human cardiomyocytes remains poorly known. We measured the electrical activities of human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) upon irradiation with 0, 20, 25, 30, 40, and 50 Gy using a multi-electrode array, and cardiomyocyte function gene levels were evaluated. iPSC-CMs showed to recover their electrophysiological activities (total active electrode, spike amplitude and slope, and corrected field potential duration) within 3–6 h from the acute effects of high-dose irradiation. The beat rate immediately increased until 3 h after irradiation, but it steadily decreased afterward. Conduction velocity slowed in cells irradiated with ≥25 Gy until 6–12 h and recovered within 24 h; notably, 20 and 25 Gy-treated groups showed subsequent continuous increase. At day 7 post-irradiation, except for cTnT, cardiomyocyte function gene levels increased with increasing irradiation dose, but uniquely peaked at 25–30 Gy. Altogether, high-dose irradiation immediately and reversibly modifies the electrical conduction of cardiomyocytes. Thus, compensatory mechanisms at the cellular level may be activated after the high-dose irradiation acute effects, thereby, contributing to the immediate antiarrhythmic outcome of cardiac radioablation for refractory ventricular arrhythmias.
Molecular and Clinical Implications of Variant Repeats in Myotonic Dystrophy Type 1
Authors: Peric Stojan , Pesovic Jovan , Savic-Pavicevic Dusanka , Rakocevic Stojanovic Vidosava , Meola Giovanni
Published: December 2021

Myotonic dystrophy type 1 (DM1) is one of the most variable monogenic diseases at phenotypic, genetic, and epigenetic level. The disease is multi-systemic with the age at onset ranging from birth to late age. The underlying mutation is an unstable expansion of CTG repeats in the DMPK gene, varying in size from 50 to >1000 repeats. Generally, large expansions are associated with an earlier age at onset. Additionally, the most severe, congenital DM1 form is typically associated with local DNA methylation. Genetic variability of DM1 mutation is further increased by its structural variations due to presence of other repeats (e.g., CCG, CTC, CAG). These variant repeats or repeat interruptions seem to confer an additional level of epigenetic variability since local DNA methylation is frequently associated with variant CCG repeats independently of the expansion size. The effect of repeat interruptions on DM1 molecular pathogenesis is not investigated enough. Studies on patients indicate their stabilizing effect on DMPK expansions because no congenital cases were described in patients with repeat interruptions, and the age at onset is frequently later than expected. Here, we review the clinical relevance of repeat interruptions in DM1 and genetic and epigenetic characteristics of interrupted DMPK expansions based on patient studies.
Information Diffusion Model in Twitter: A Systematic Literature Review
Authors: Firdaniza Firdaniza , Ruchjana Budi , Chaerani Diah , Radianti Jaziar
Published: December 2021

Information diffusion, information spread, and influencers are important concepts in many studies on social media, especially Twitter analytics. However, literature overviews on the information diffusion of Twitter analytics are sparse, especially on the use of continuous time Markov chain (CTMC). This paper examines the following topics: (1) the purposes of studies about information diffusion on Twitter, (2) the methods adopted to model information diffusion on Twitter, (3) the metrics applied, and (4) measures used to determine influencer rankings. We employed a systematic literature review (SLR) to explore the studies related to information diffusion on Twitter extracted from four digital libraries. In this paper, a two-stage analysis was conducted. First, we implemented a bibliometric analysis using VOSviewer and R-bibliometrix software. This approach was applied to select 204 papers after conducting a duplication check and assessing the inclusion–exclusion criteria. At this stage, we mapped the authors’ collaborative networks/collaborators and the evolution of research themes. Second, we analyzed the gap in research themes on the application of CTMC information diffusion on Twitter. Further filtering criteria were applied, and 34 papers were analyzed to identify the research objectives, methods, metrics, and measures used by each researcher. Nonhomogeneous CTMC has never been used in Twitter information diffusion modeling. This finding motivates us to further study nonhomogeneous CTMC as a modeling approach for Twitter information diffusion.
Overview of the Development and Use of Akt Inhibitors in Prostate Cancer
Authors: Gasmi Anis , Roubaud Guilhem , Dariane Charles , Barret Eric , Beauval Jean-Baptiste , Brureau Laurent , Créhange Gilles , Fiard Gaëlle , Fromont Gaëlle , Gauthé Mathieu , Ruffion Alain , Renard-Penna Raphaële , Sargos Paul , Rouprêt Morgan , Ploussard Guillaume , Mathieu Romain
Published: December 2021

Deregulation of the PI3K-Akt-mTOR pathway plays a critical role in the development and progression of many cancers. In prostate cancer, evidence suggests that it is mainly driven by PTEN loss of function. For many years, the development of selective Akt inhibitors has been challenging. In recent phase II and III clinical trials, Ipatasertib and Capivasertib associated with androgen deprivation therapies showed promising outcomes in patients with metastatic castration-resistant prostate cancer and PTEN-loss. Ongoing trials are currently assessing several Akt inhibitors in prostate cancer with different combinations, at different stages of the disease.
The ED-PLANN Score: A Simple Risk Stratification Tool for Out-of-Hospital Cardiac Arrests Derived from Emergency Departments in Korea
Authors: Lim Hyouk Jae , Ro Young Sun , Kim Ki Hong , Park Jeong Ho , Hong Ki Jeong , Song Kyoung Jun , Shin Sang Do
Published: December 2021

Early risk stratification of out-of-hospital cardiac arrest (OHCA) patients with insufficient information in emergency departments (ED) is difficult but critical in improving intensive care resource allocation. This study aimed to develop a simple risk stratification score using initial information in the ED. Adult patients who had OHCA with medical etiology from 2016 to 2020 were enrolled from the Korean Cardiac Arrest Research Consortium (KoCARC) database. To develop a scoring system, a backward logistic regression analysis was conducted. The developed scoring system was validated in both external dataset and internal bootstrap resampling. A total of 8240 patients were analyzed, including 4712 in the development cohort and 3528 in the external validation cohort. An ED-PLANN score (range 0–5) was developed incorporating 1 point for each: P for serum pH ≤ 7.1, L for serum lactate ≥ 10 mmol/L, A for age ≥ 70 years old, N for non-shockable rhythm, and N for no-prehospital return of spontaneous circulation. The area under the receiver operating characteristics curve (AUROC) for favorable neurological outcome was 0.93 (95% CI, 0.92–0.94) in the development cohort, 0.94 (95% CI, 0.92–0.95) in the validation cohort. Hosmer–Lemeshow goodness-of-fit tests also indicated good agreement. The ED-PLANN score is a practical and easily applicable clinical scoring system for predicting favorable neurological outcomes of OHCA patients.
Slt2-MAPK/RNS1 Controls Conidiation via Direct Regulation of the Central Regulatory Pathway in the Fungus Metarhizium robertsii
Authors: Meng Yamin , Tang Xingyuan , Bao Yuting , Zhang Mingxiang , Tang Dan , Zhang Xing , Chen Xiaoxuan , Fang Weiguo
Published: December 2021

Ascomycete fungi usually produce small hydrophobic asexual conidia that are easily dispersed and essential for long-term survival under a variety of environmental conditions. Several upstream signaling regulators have been documented to control conidiation via regulation of the central regulatory pathway that contains the transcription factors BrlA, AbaA and WetA. Here, we showed that the Slt2-MAPK signaling pathway and the transcription factor RNS1 constitute a novel upstream signaling cascade that activates the central regulatory pathway for conidiation in the Ascomycetes fungus M. robertsii. The BrlA gene has two overlapping transcripts BrlAα and BrlAβ; they have the same major ORF, but the 5’ UTR of BrlAβ is 835 bp longer than the one of BrlAα. During conidiation, Slt2 phosphorylates the serine residue at the position 306 in RNS1, which self-induces. RNS1 binds to the BM2 motif in the promoter of the BrlA gene and induces the expression of the transcript BlrAα, which in turn activates the expression of the genes AbaA and WetA. In conclusion, the Slt2/RNS1 cascade represents a novel upstream signaling pathway that initiates conidiation via direct activation of the central regulatory pathway. This work provides significant mechanistic insights into the production of asexual conidia in an Ascomycete fungus.
Recent Developments in Metabolomics Studies of Endophytic Fungi
Authors: Nagarajan Kashvintha , Ibrahim Baharudin , Ahmad Bawadikji Abdulkader , Lim Jun-Wei , Tong Woei-Yenn , Leong Chean-Ring , Khaw Kooi Yeong , Tan Wen-Nee
Published: December 2021

Endophytic fungi are microorganisms that colonize living plants’ tissues without causing any harm. They are known as a natural source of bioactive metabolites with diverse pharmacological functions. Many structurally different chemical metabolites were isolated from endophytic fungi. Recently, the increasing trends in human health problems and diseases have escalated the search for bioactive metabolites from endophytic fungi. The conventional bioassay-guided study is known as laborious due to chemical complexity. Thus, metabolomics studies have attracted extensive research interest owing to their potential in dealing with a vast number of metabolites. Metabolomics coupled with advanced analytical tools provides a comprehensive insight into systems biology. Despite its wide scientific attention, endophytic fungi metabolomics are relatively unexploited. This review highlights the recent developments in metabolomics studies of endophytic fungi in obtaining the global metabolites picture.
The Interaction among Microbiota, Epigenetic Regulation, and Air Pollutants in Disease Prevention
Authors: Pulliero Alessandra , Traversi Deborah , Franchitti Elena , Barchitta Martina , Izzotti Alberto , Agodi Antonella
Published: December 2021

Environmental pollutants can influence microbiota variety, with important implications for the general wellbeing of organisms. In subjects at high-risk of cancer, gut, and lung microbiota are distinct from those of low-risk subjects, and disease progression is associated with microbiota alterations. As with many inflammatory diseases, it is the combination of specific host and environmental factors in certain individuals that provokes disease outcomes. The microbiota metabolites influence activity of epigenetic enzymes. The knowledge of the mechanisms of action of environmental pollution now includes not only the alteration of the gut microbiota but also the interaction between different human microbiota niches such as the lung–gut axis. The epigenetic regulations can reprogram differentiated cells in response to environmental changes. The microbiota can play a major role in the progression and suppression of several epigenetic diseases. Accordingly, the maintenance of a balanced microbiota by monitoring the environmental stimuli provides a novel preventive approach for disease prevention. Metagenomics technologies can be utilized to establish new mitigation approaches for diseases induced by polluted environments. The purpose of this review is to examine the effects of particulate matter exposure on the progression of disease outcomes as related to the alterations of gut and lung microbial communities and consequent epigenetic modifications.