bluuebunny/crossref_metadata_2025 huggingface dataset:
Household Financial Vulnerability to Income and Medical Expenditure Shocks: Measurement and Determinants
Authors: He Lei , Zhou Shuyi
Published: April 2022

This paper proposes a novel ex ante indicator to measure the degree of household financial vulnerability by calculating the probability of falling into financial distress under uncertain income and medical expenditure. The advantage of this measure is that it can reflect the capacity of households to deal with income shock and medical expenditure shock and quantify the degree of financial vulnerability for households beforehand. We employ it to measure the financial vulnerability of Chinese urban and rural households separately by using data from the China Health and Retirement Longitudinal Study (CHARLS) 2011, 2013, and 2015. Further, we analyze the potential determinants and their contributions to financial vulnerability changes. We find that rural households experience higher financial vulnerability than urban households. Furthermore, the investigation into the effects of potential determinants suggests that demographic variables (including age, gender, education, marital status, household size, labor force, and area), health-related variables (including health status, disability, and health shock), and medical insurance variables (including urban employee medical insurance and commercial medical insurance) have significant effects on the financial vulnerability of both urban and rural households. Contribution analysis of the determinants of household financial vulnerability shows that variables including disability, health shock, household size, labor force, and education contribute most to the changes in financial vulnerability.
Application of Personalized Education in the Mobile Medical App for Breast Self-Examination
Authors: Błajda Joanna , Barnaś Edyta , Kucab Anna
Published: April 2022

Introduction. Mobile apps are considered intelligent tools useful in various areas of public health. The social dimension of breast cancer and the current epidemic situation require tools that may increase knowledge and improve the skills in the field of breast self-examination. The study aims to assess the use of personalized education based on algorithms with conditions in the mobile medical app for breast self-examination. Materials and methods. In total, 500 women from the Podkarpackie Province were enrolled in the study, which was a representative group for the inhabitants of this province. The subjects were randomly divided into two groups (group I: the study group including 250 people; group II: the controls of 250 people). The study group was subjected to intervention, which was personalized education on breast cancer. The method was a proprietary mobile medical app based on algorithms with conditions. The study was carried out from March 2018 to February 2019. Results. The majority of women, 77.8% (N = 389), were under 30 years of age. Only a small amount of the breast area was marked in the tactile test in both groups. In the study group, the average number of selected points was 14.86 (7.43% of the area to be examined), while in the control group it amounted to 9.14 (4.57%). The area most commonly examined in Test I in both groups was the central area of the mammary gland with the nipple. After the intervention in Test II, women from the study group marked a significantly greater area in the tactile test than women from the control group (χ2 = 99.733; df = 6; p < 0.0001). The mean result in the study group was 22.10, while in the control group it amounted to 9.10. It was found that the breast area marked in both tests depended solely on the women’s knowledge about breast cancer (p < 0.001). It was also found that the higher the risk of developing breast cancer, the more points in Test I were indicated by the women in the tactile test (p = 0.0122). Conclusions. Educational mobile medical apps for breast cancer prevention may help to deal with breast cancer, which is an important public health issue. It is also important to broaden the possibilities of medical apps for breast self-examination with elements verifying the skills of the three-stage compression of the examined breast.
The Association between Childhood Exposure to Ambient Air Pollution and Obesity: A Systematic Review and Meta-Analysis
Authors: Huang Chao , Li Cheng , Zhao Fengyi , Zhu Jing , Wang Shaokang , Sun Guiju
Published: April 2022

Obesity has become a worldwide epidemic; 340 million of children and adolescents were overweight or obese in 2016, and this number continues to grow at a rapid rate. Epidemiological research has suggested that air pollution affects childhood obesity and weight status, but the current evidence remains inconsistent. Therefore, the aim of this meta-analysis was to estimate the effects of childhood exposure to air pollutants on weight. A total of four databases (PubMed, Web of Science, Embase, and Cochrane Library) were searched for publications up to December 31, 2021, and finally 15 studies met the inclusion criteria for meta-analysis. Merged odds ratios (ORs), coefficients (β), and 95% confidence intervals (95% CIs) that were related to air pollutants were estimated using a random-effects model. The meta-analysis indicated that air pollutants were correlated with childhood obesity and weight gain. For obesity, the association was considerable for PM10 (OR = 1.12, 95% CI: 1.06, 1.18), PM2.5 (OR = 1.28, 95% CI: 1.13, 1.45), PM1 (OR = 1.41, 95% CI: 1.30, 1.53), and NO2 (OR = 1.11, 95% CI: 1.06, 1.18). Similarly, BMI status increased by 0.08 (0.03–0.12), 0.11 (0.05–0.17), and 0.03 (0.01–0.04) kg/m2 with 10 μg/m3 increment in exposure to PM10, PM2.5, and NO2. In summary, air pollution can be regarded as a probable risk factor for the weight status of children and adolescents. The next step is to conduct longer-term and large-scale studies on different population subgroups, exposure concentrations, and pollutant combinations to provide detailed evidence. Meanwhile, integrated management of air pollution is essential.
A Review of Historical Changes of Tropical and Extra-Tropical Cyclones: A Comparative Analysis of the United States, Europe, and Asia
Authors: Lau Yui-Yip , Yip Tsz-Leung , Dulebenets Maxim A. , Tang Yuk-Ming , Kawasaki Tomoya
Published: April 2022

Tropical cyclones are highly destructive weather systems, especially in coastal areas. Tropical cyclones with maximum sustained winds exceeding 74 mph (≈119 kph) are classified as typhoons in the Northwest Pacific, whilst the term ‘hurricanes’ applies to other regions. This study aims to investigate the general characteristics of the most devastating and catastrophic tropical cyclones in the USA Europe, and Asia. To achieve the study objectives, the three most devastating typical tropical cyclones in each region were selected. The tropical cyclones were examined based on various features, such as the number of deaths, minimum pressure, highest wind speed, total financial losses, and frequency per year. In contrast to Europe and Asia, the USA has recorded the highest number of catastrophic tropical cyclones. The damage induced by hurricanes Katrina, Harvey, and Maria in the USA totalled approximately USD USD 380 billion. In addition, the present research highlights the demand to improve the public attitude and behaviour toward the impact of climate change along with the enhancement of climate change alleviation strategies. The number of intense tropical cyclones is expected to rise, and the tropical cyclone-related precipitation rate is expected to increase in warmer-climate areas. Stakeholders and industrial practitioners may use the research findings to design resilience and adaptation plans in the face of tropical cyclones, allowing them to assess the effects of climate change on tropical cyclone incidents from an academic humanitarian logistics viewpoint in the forthcoming years.
The Effects of Urban Neighborhood Environmental Evaluation and Health Service Facilities on Residents’ Self-Rated Physical and Mental Health: A Comparative and Empirical Survey
Authors: Wan Jiangjun , Zhao Yutong , Chen Yun , Wang Yanlan , Su Yi , Song Xueqian , Zhang Shaoyao , Zhang Chengyan , Zhu Wei , Yang Jinxiu
Published: April 2022

(1) Background: The neighborhood environment has been shown to be an essential factor affecting residents’ quality of life and health, but the relationship between the characteristics of health service facilities and health levels is rarely known. (2) Methods: This study used a representative sample (n = 591, 303 women; 288 men, age 18–85 years, lived in Chengdu for an extensive time) of residents living in Chengdu City, China, and took spatial point data and empirical research data to construct an ordered logistic regression model. We contrastively analyzed the influence of different variables in the neighborhood environment and health service facilities on self-rated physical health (SRPH) and self-rated mental health (SRMH). (3) Results: The frequency of use and accessibility of multiple facilities in the health service facilities were significantly associated with self-rated health (SRH). Significant differences occurred between residents’ perceived accessibility and actual accessibility of facilities in SRH. Comparing the results of SRPH and SRMH revealed that the influencing factors that affect the two vary. The factors that significantly affect SRMH include neighborhood physical environment evaluation; social environmental evaluation; the frequency of use of the parks and squares, and sports zones; and the accessibility of parks and squares, specialized hospitals, community hospitals, and pharmacies. However, the factors that significantly affect SRPH include the frequency of use of sports venues, general hospitals, and pharmacies and the accessibility of general hospitals. The social environment of the neighborhood is also a non-negligible part, and its interaction with the physical environment of the neighborhood affects the outcome of SRH. (4) Conclusions: Neighborhood environmental characteristics and the layout of health service facilities have significant differential effects on people’s physical and psychological health, and this information is of great value in promoting healthy city development and improving the quality of life of urban populations around the world.
Pregnant Women’s Knowledge of and Attitudes towards Influenza Vaccination during the COVID-19 Pandemic in Poland
Authors: Pisula Agata , Sienicka Agnieszka , Pawlik Katarzyna Karina , Dobrowolska-Redo Agnieszka , Kacperczyk-Bartnik Joanna , Romejko-Wolniewicz Ewa
Published: April 2022

Pregnant women are more susceptible to influenza virus infections due to the immunological and physiological changes in the course of pregnancy. Vaccination during pregnancy is a safe and effective method for protecting both the mothers and the infants from influenza and its complications. This study was conducted in order to determine the knowledge and attitudes of Polish pregnant women towards influenza vaccination during the COVID-19 pandemic. A questionnaire-based and self-administered study was carried out fully online and a total of 515 women participated. A total of 52% (n = 268) of surveyed women answered that vaccination against influenza during pregnancy was safe. However, only 21% (n = 108) were vaccinated against influenza during their current pregnancy and 17.5% (n = 90) intended to be vaccinated. The participants indicated many concerns about getting vaccinated during pregnancy, but also many benefits that come with the vaccination. General knowledge about influenza, its complications, and vaccination was quite high in the study group.
Temporal and Spatial Analysis of Alzheimer’s Disease Based on an Improved Convolutional Neural Network and a Resting-State FMRI Brain Functional Network
Authors: Sun Haijing , Wang Anna , He Shanshan
Published: April 2022

Most current research on Alzheimer’s disease (AD) is based on transverse measurements. Given the nature of neurodegeneration in AD progression, observing longitudinal changes in the structural features of brain networks over time may improve the accuracy of the predicted transformation and provide a good measure of the progression of AD. Currently, there is no cure for patients with existing AD dementia, but patients with mild cognitive impairment (MCI) in the prodromal stage of AD dementia may be diagnosed. The study of the early diagnosis of MCI and the prediction of MCI to AD transformation is of great significance for the monitoring of the MCI to AD transformation process. Despite the high rate of MCI conversion to AD, the neuropathological cause of MCI is heterogeneous. However, many people with MCI remain stable. Treatment options are different for patients with stable MCI and those with underlying dementia. Therefore, it is of great significance for clinical practice to predict whether patients with MCI will develop AD dementia. This paper proposes an improved algorithm that is based on a convolution neural network (CNN) with residuals combined with multi-layer long short-term memory (LSTM) to diagnose AD and predict MCI. Firstly, multi-time resting-state fMRI images were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database for preprocessing, and then an AAL brain partition template was used to construct a 90 × 90 functional connectivity (FC) network matrix of a whole-brain region of interest (ROI). Secondly, the diversity of training samples was increased by generating an adversarial network (GAN). Finally, a CNN with residuals and a multi-layer LSTM model were constructed to automatically classify and predict the functional adjacency matrix. This method can not only distinguish Alzheimer’s disease from normal health conditions at multiple time points, but can also predict progressive MCI (pMCI) and stable MCI (sMCI) at multiple time points. The classification accuracies in AD vs. NC and sMCI vs.pMCI reached 93.5% and 75.5%, respectively.
COVID-19 and the Elderly’s Mental Illness: The Role of Risk Perception, Social Isolation, Loneliness and Ageism
Authors: Donizzetti Anna Rosa , Lagacé Martine
Published: April 2022

For almost two years, populations around the globe faced precariousness and uncertainty as a result of the COVID-19 pandemic. Older adults were highly affected by the virus, and the policies meant to protect them have often resulted in ageist stereotypes and discrimination. For example, the public discourse around older adults had a paternalistic tone framing all older adults as “vulnerable”. This study aimed to measure the extent to which perceived age discrimination in the context of the COVID-19 pandemic, as well as the sense of loneliness and social isolation, fear and perception of COVID-19 risks, had a negative effect on older adults’ mental illness. To do so, a self-report questionnaire was administered to 1301 participants (average age: 77.25 years old, SD = 5.46; 56.10% females, 43.90% males). Descriptive and correlational analyses were performed, along with structural equation modelling. Results showed that perceived age discrimination in the context of the COVID-19 pandemic positively predicts loneliness and also indirectly predicts mental illness. In addition, loneliness is the strongest predictor of mental illness together with fear of COVID-19 and social isolation. Such results highlight the importance of implementing public policies and discourses that are non-discriminating, and that favour the inclusion of older people.
Traditional and Undulating Periodization on Body Composition, Strength Levels and Physical Fitness in Older Adults
Authors: Vargas-Molina Salvador , García-Sillero Manuel , Romance Ramón , Petro Jorge L. , Jiménez-García José Daniel , Bonilla Diego A. , Kreider Richard B. , Benítez-Porres Javier
Published: April 2022

Introduction: Undulating training has been investigated in sedentary and trained adults, but less is known about the influence of undulating training in older adults. Purpose: This study aimed to evaluate body composition, strength levels, and physical fitness in response to traditional or undulating training in older adults. Methods: A controlled, double-arm trial was conducted in eighteen older adults (10 males, 8 females; 64 ± 2.1 years; 165.12 ± 7.5 cm; 72.5 ± 11.4 kg; 26.5 ± 3.2 k·gm−2) who were randomly assigned to traditional (n = 9, TT) or undulating training (n = 9, UT) for eight weeks. Dual X-ray absorptiometry was used to measure fat-free mass (FFM), fat mass (FM), and bone mineral density (BMD). Strength levels were evaluated by the handgrip strength and the one-repetition maximum in vertical chest press, rowing machine, squat, monopodal horizontal leg press, and leg extension. In addition, functional capacity was assessed using the Senior Fitness Test (SFT). Statistical analysis included mean/median comparisons to establish the difference after the intervention (paired Student’s t-test or Wilcoxon test), and effect size calculations based on estimates. Results: After correction for fat-free adipose tissue, a significant increase in FFM was observed in both groups, while no significant changes were found in FM and BMD. Upper- and lower-limbs strength showed significant increases in both groups, although clinical significance varied among exercises. Favorable results were seen on the cardiorespiratory fitness and strength components of the SFT in both groups. Conclusions: The 8-week UT and TT protocols are valid options for improving FFM and increasing strength and functional capacity in women and men over 60 years of age.
Controversies in the Pathogenesis, Diagnosis and Treatment of PCOS: Focus on Insulin Resistance, Inflammation, and Hyperandrogenism
Authors: Armanini Decio , Boscaro Marco , Bordin Luciana , Sabbadin Chiara
Published: April 2022

Polycystic ovary syndrome (PCOS) is a heterogeneous and extremely common disease with symptoms that vary with the age of the patient, typically characterized by hyperandrogenism, chronic oligo-anovulation, and/or several metabolic disorders. The syndrome includes various phenotypes, and the pathogenesis is multifactorial, often involving insulin resistance. This feature is closely related to ovarian dysfunction, inflammation, hyperandrogenism, and metabolic disorders, which characterize and complicate the syndrome. Therapy currently considers both lifestyle improvements and medications, and must be tailored on a case-by-case basis. To date, the published studies have not arrived at a definition of the most suitable therapy for each individual case and many of the drugs used are still off-label. In this review, we discuss some controversial diagnostic and therapeutic aspects of PCOS, such as the role of insulin resistance, inflammation, and hyperandrogenism. We also evaluated the advantages and disadvantages of contraceptive therapy and antiandrogens.
Genome-Wide Identification, Expansion, and Evolution Analysis of Homeobox Gene Family Reveals TALE Genes Important for Secondary Cell Wall Biosynthesis in Moso Bamboo (Phyllostachys edulis)
Authors: Que Feng , Liu Qingnan , Zha Ruofei , Xiong Aisheng , Wei Qiang
Published: April 2022

The TALE gene family is a subfamily of the homeobox gene family and has been implicated in regulating plant secondary growth. However, reports about the evolutionary history and function of the TALE gene family in bamboo are limited. Here, the homeobox gene families of moso bamboo Olyra latifolia and Bonia amplexicaulis were identified and compared. Many duplication events and obvious expansions were found in the TALE family of woody bamboo. PhTALEs were found to have high syntenies with TALE genes in rice. Through gene co-expression analysis and quantitative real-time PCR analysis, the candidate PhTALEs were thought to be involved in regulating secondary cell wall development of moso bamboo during the fast-growing stage. Among these candidate PhTALEs, orthologs of OsKNAT7, OSH15, and SH5 in moso bamboo may regulate xylan synthesis by regulating the expression of IRX-like genes. These results suggested that PhTALEs may participate in the secondary cell wall deposition in internodes during the fast-growing stage of moso bamboo. The expansion of the TALE gene family may be implicated in the increased lignification of woody bamboo when divergent from herbaceous bamboos.
Colocalization and Interaction Study of Neuronal JNK3, JIP1, and β-Arrestin2 Together with PSD95
Authors: Musi Clara Alice , Marchini Giacomo , Giani Arianna , Tomaselli Giovanni , Priori Erica Cecilia , Colnaghi Luca , Borsello Tiziana
Published: April 2022

c-Jun N-terminal kinases (JNKs) are stress-activated serine/threonine protein kinases belonging to the mitogen-activated protein kinase (MAPK) family. Among them, JNK3 is selectively expressed in the central nervous system, cardiac smooth muscle, and testis. In addition, it is the most responsive JNK isoform to stress stimuli in the brain, and it is involved in synaptic dysfunction, an essential step in neurodegenerative processes. JNK3 pathway is organized in a cascade of amplification in which signal transduction occurs by stepwise, highly controlled phosphorylation. Since different MAPKs share common upstream activators, pathway specificity is guaranteed by scaffold proteins such as JIP1 and β-arrestin2. To better elucidate the physiological mechanisms regulating JNK3 in neurons, and how these interactions may be involved in synaptic (dys)function, we used (i) super-resolution microscopy to demonstrate the colocalization among JNK3–PSD95–JIP1 and JNK3–PSD95–β-arrestin2 in cultured hippocampal neurons, and (ii) co-immunoprecipitation techniques to show that the two scaffold proteins and JNK3 can be found interacting together with PSD95. The protein-protein interactions that govern the formation of these two complexes, JNK3–PSD95–JIP1 and JNK3–PSD95–β-arrestin2, may be used as targets to interfere with their downstream synaptic events.
Identification of Secreted Protein Gene-Based SNP Markers Associated with Virulence Phenotypes of Puccinia striiformis f. sp. tritici, the Wheat Stripe Rust Pathogen
Authors: Bai Qing , Wang Meinan , Xia Chongjing , See Deven R. , Chen Xianming
Published: April 2022

Stripe rust caused by Puccinia striiformis f. sp. tritici (Pst) is a destructive disease that occurs throughout the major wheat-growing regions of the world. This pathogen is highly variable due to the capacity of virulent races to undergo rapid changes in order to circumvent resistance in wheat cultivars and genotypes and to adapt to different environments. Intensive efforts have been made to study the genetics of wheat resistance to this disease; however, no known avirulence genes have been molecularly identified in Pst so far. To identify molecular markers for avirulence genes, a Pst panel of 157 selected isolates representing 126 races with diverse virulence spectra was genotyped using 209 secreted protein gene-based single nucleotide polymorphism (SP-SNP) markers via association analysis. Nineteen SP-SNP markers were identified for significant associations with 12 avirulence genes: AvYr1, AvYr6, AvYr7, AvYr9, AvYr10, AvYr24, AvYr27, AvYr32, AvYr43, AvYr44, AvYrSP, and AvYr76. Some SP-SNPs were associated with two or more avirulence genes. These results further confirmed that association analysis in combination with SP-SNP markers is a powerful tool for identifying markers for avirulence genes. This study provides genomic resources for further studies on the cloning of avirulence genes, understanding the mechanisms of host–pathogen interactions, and developing functional markers for tagging specific virulence genes and race groups.
Role of Polymer Concentration and Crosslinking Density on Release Rates of Small Molecule Drugs
Authors: Briggs Francesca , Browne Daryn , Asuri Prashanth
Published: April 2022

Over the past few years, researchers have demonstrated the use of hydrogels to design drug delivery platforms that offer a variety of benefits, including but not limited to longer circulation times, reduced drug degradation, and improved targeting. Furthermore, a variety of strategies have been explored to develop stimulus-responsive hydrogels to design smart drug delivery platforms that can release drugs to specific target areas and at predetermined rates. However, only a few studies have focused on exploring how innate hydrogel properties can be optimized and modulated to tailor drug dosage and release rates. Here, we investigated the individual and combined roles of polymer concentration and crosslinking density (controlled using both chemical and nanoparticle-mediated physical crosslinking) on drug delivery rates. These experiments indicated a strong correlation between the aforementioned hydrogel properties and drug release rates. Importantly, they also revealed the existence of a saturation point in the ability to control drug release rates through a combination of chemical and physical crosslinkers. Collectively, our analyses describe how different hydrogel properties affect drug release rates and lay the foundation to develop drug delivery platforms that can be programmed to release a variety of bioactive payloads at defined rates.
KRAS: A Druggable Target in Colon Cancer Patients
Authors: Negri Francesca , Bottarelli Lorena , de’Angelis Gian Luigi , Gnetti Letizia
Published: April 2022

Mutations in KRAS are among the most frequent aberrations in cancer, including colon cancer. KRAS direct targeting is daunting due to KRAS protein resistance to small molecule inhibition. Moreover, its elevated affinity to cellular guanosine triphosphate (GTP) has made the design of specific drugs challenging. Indeed, KRAS was considered ‘undruggable’. KRASG12C is the most commonly mutated variant of KRAS in non-small cell lung cancer. Currently, the achievements obtained with covalent inhibitors of this variant have given the possibility to assess the best therapeutic approach to KRAS-driven tumors. Mutation-related biochemical assets and the tissue of origin are expected to influence responses to treatment. Further attempts to obtain mutant-specific KRAS (KRASG12C) switch-II covalent inhibitors are ongoing and the results are promising. Drugs targeted to block KRAS effector pathways could be combined with direct KRAS inhibitors, immunotherapy or T cell-targeting approaches in KRAS-mutant tumors. The development of valuable combination regimens will be essential against potential mechanisms of resistance that may arise during treatment.
The Anti-Inflammatory Properties of Licorice (Glycyrrhiza glabra)-Derived Compounds in Intestinal Disorders
Authors: Leite Camila dos Santos , Bonafé Gabriel Alves , Carvalho Santos Juliana , Martinez Carlos Augusto Real , Ortega Manoela Marques , Ribeiro Marcelo Lima
Published: April 2022

Intestinal diseases, such as inflammatory bowel diseases (IBDs) and colorectal cancer (CRC), are a significant source of morbidity and mortality worldwide. Epidemiological data have shown that IBD patients are at an increased risk for the development of CRC. IBD-associated cancer develops against a background of chronic inflammation and oxidative stress, and their products contribute to cancer development and progression. Therefore, the discovery of novel drugs for the treatment of intestinal diseases is urgently needed. Licorice (Glycyrrhiza glabra) has been largely used for thousands of years in traditional Chinese medicine. Licorice and its derived compounds possess antiallergic, antibacterial, antiviral, anti-inflammatory, and antitumor effects. These pharmacological properties aid in the treatment of inflammatory diseases. In this review, we discuss the pharmacological potential of bioactive compounds derived from Licorice and addresses their anti-inflammatory and antioxidant properties. We also discuss how the mechanisms of action in these compounds can influence their effectiveness and lead to therapeutic effects on intestinal disorders.
Perspectives for Primary Ciliary Dyskinesia
Authors: Bukowy-Bieryllo Zuzanna , Witt Michal , Zietkiewicz Ewa
Published: April 2022

Primary ciliary dyskinesia (PCD) is a ciliopathy caused by genetically determined impairment of motile cilia–organelles present on the surface of many types of cells [...]
The Characters of Non-Coding RNAs and Their Biological Roles in Plant Development and Abiotic Stress Response
Authors: Ma Xu , Zhao Fei , Zhou Bo
Published: April 2022

Plant growth and development are greatly affected by the environment. Many genes have been identified to be involved in regulating plant development and adaption of abiotic stress. Apart from protein-coding genes, more and more evidence indicates that non-coding RNAs (ncRNAs), including small RNAs and long ncRNAs (lncRNAs), can target plant developmental and stress-responsive mRNAs, regulatory genes, DNA regulatory regions, and proteins to regulate the transcription of various genes at the transcriptional, posttranscriptional, and epigenetic level. Currently, the molecular regulatory mechanisms of sRNAs and lncRNAs controlling plant development and abiotic response are being deeply explored. In this review, we summarize the recent research progress of small RNAs and lncRNAs in plants, focusing on the signal factors, expression characters, targets functions, and interplay network of ncRNAs and their targets in plant development and abiotic stress responses. The complex molecular regulatory pathways among small RNAs, lncRNAs, and targets in plants are also discussed. Understanding molecular mechanisms and functional implications of ncRNAs in various abiotic stress responses and development will benefit us in regard to the use of ncRNAs as potential character-determining factors in molecular plant breeding.
Transportin-3 Facilitates Uncoating of Influenza A Virus
Authors: Zou Jiahui , Yu Luyao , Zhu Yinxing , Yang Shuaike , Zhao Jiachang , Zhao Yaxin , Jiang Meijun , Xie Shengsong , Liu Hailong , Zhao Changzhi , Zhou Hongbo
Published: April 2022

Influenza A viruses (IAVs) are a major global health threat and in the future, may cause the next pandemic. Although studies have partly uncovered the molecular mechanism of IAV–host interaction, it requires further research. In this study, we explored the roles of transportin-3 (TNPO3) in IAV infection. We found that TNPO3-deficient cells inhibited infection with four different IAV strains, whereas restoration of TNPO3 expression in knockout (KO) cells restored IAV infection. TNPO3 overexpression in wild-type (WT) cells promoted IAV infection, suggesting that TNPO3 is involved in the IAV replication. Furthermore, we found that TNPO3 depletion restrained the uncoating in the IAV life cycle, thereby inhibiting the process of viral ribonucleoprotein (vRNP) entry into the nucleus. However, KO of TNPO3 did not affect the virus attachment, endocytosis, or endosomal acidification processes. Subsequently, we found that TNPO3 can colocalize and interact with viral proteins M1 and M2. Taken together, the depletion of TNPO3 inhibits IAV uncoating, thereby inhibiting IAV replication. Our study provides new insights and potential therapeutic targets for unraveling the mechanism of IAV replication and treating influenza disease.
Heat-Stress Preconditioning Attenuates Behavioral Responses to Psychological Stress: The Role of HSP-70 in Modulating Stress Responses
Authors: Belity Tal , Horowitz Michal , Hoffman Jay R. , Epstein Yoram , Bruchim Yaron , Todder Doron , Cohen Hagit
Published: April 2022

Exposure to high ambient temperature is a stressor that influences both biological and behavioral functions and has been previously shown to have an extensive impact on brain structure and function. Physiological, cellular and behavioral responses to heat-stress (HS) (40–41 °C, 2 h) were evaluated in adult male Sprague-Dawley rats. The effect of HS exposure before predator-scent stress (PSS) exposure (i.e., HS preconditioning) was examined. Finally, a possible mechanism of HS-preconditioning to PSS was investigated. Immunohistochemical analyses of chosen cellular markers were performed in the hippocampus and in the hypothalamic paraventricular nucleus (PVN). Plasma corticosterone levels were evaluated, and the behavioral assessment included the elevated plus-maze (EPM) and the acoustic startle response (ASR) paradigms. Endogenous levels of heat shock protein (HSP)-70 were manipulated using an amino acid (L-glutamine) and a pharmacological agent (Doxazosin). A single exposure to an acute HS resulted in decreased body mass (BM), increased body temperature and increased corticosterone levels. Additionally, extensive cellular, but not behavioral changes were noted. HS-preconditioning provided behavioral resiliency to anxiety-like behavior associated with PSS, possibly through the induction of HSP-70. Targeting of HSP-70 is an attractive strategy for stress-related psychopathology treatment.
Neferine, an Alkaloid from Lotus Seed Embryos, Exerts Antiseizure and Neuroprotective Effects in a Kainic Acid-Induced Seizure Model in Rats
Authors: Lin Tzu-Yu , Hung Chih-Yu , Chiu Kuan-Ming , Lee Ming-Yi , Lu Cheng-Wei , Wang Su-Jane
Published: April 2022

Current anti-seizure drugs fail to control approximately 30% of epilepsies. Therefore, there is a need to develop more effective anti-seizure drugs, and medicinal plants provide an attractive source for new compounds. This study aimed to evaluate the possible anti-seizure and neuroprotective effects of neferine, an alkaloid from the lotus seed embryos of Nelumbo nucifera, in a kainic acid (KA)-induced seizure rat model and its underlying mechanisms. Rats were intraperitoneally (i.p.) administrated neferine (10 and 50 mg/kg) 30 min before KA injection (15 mg/kg, i.p.). Neferine pretreatment increased seizure latency and reduced seizure scores, prevented glutamate elevation and neuronal loss, and increased presynaptic protein synaptophysin and postsynaptic density protein 95 expression in the hippocampi of rats with KA. Neferine pretreatment also decreased glial cell activation and proinflammatory cytokine (interleukin-1β, interleukin-6, tumor necrosis factor-α) expression in the hippocampi of rats with KA. In addition, NOD-like receptor 3 (NLRP3) inflammasome, caspase-1, and interleukin-18 expression levels were decreased in the hippocampi of seizure rats pretreated with neferine. These results indicated that neferine reduced seizure severity, exerted neuroprotective effects, and ameliorated neuroinflammation in the hippocampi of KA-treated rats, possibly by inhibiting NLRP3 inflammasome activation and decreasing inflammatory cytokine secretion. Our findings highlight the potential of neferine as a therapeutic option in the treatment of epilepsy.
Circular RNAs: Emblematic Players of Neurogenesis and Neurodegeneration
Authors: D’Anca Marianna , Buccellato Francesca R. , Fenoglio Chiara , Galimberti Daniela
Published: April 2022

In the fascinating landscape of non-coding RNAs (ncRNAs), circular RNAs (circRNAs) are peeping out as a new promising and appreciated class of molecules with great potential as diagnostic and prognostic biomarkers. They come from circularization of single-stranded RNA molecules covalently closed and generated through alternative mRNA splicing. Dismissed for many years, similar to aberrant splicing by-products, nowadays, their role has been regained. They are able to regulate the expression of linear mRNA transcripts at different levels acting as miRNA sponges, interacting with ribonucleoproteins or exerting a control on gene expression. On the other hand, being extremely conserved across phyla and stable, cell and tissue specific, mostly abundant than the linear RNAs, it is not surprising that they should have critical biological functions. Curiously, circRNAs are particularly expressed in brain and they build up during aging and age-related diseases. These extraordinary peculiarities make circRNAs potentially suitable as promising molecular biomarkers, especially of aging and neurodegenerative diseases. This review aims to explore new evidence on circRNAs, emphasizing their role in aging and pathogenesis of major neurodegenerative disorders, Alzheimer’s disease, frontotemporal dementia, and Parkinson’s diseases with a look toward their potential usefulness in biomarker searching.
Identification of WxL and S-Layer Proteins from Lactobacillus brevis with the Ability to Bind Cellulose and Xylan
Authors: Hao Zhenzhen , Zhang Wenjing , Wang Xiaolu , Wang Yuan , Qin Xing , Luo Huiying , Huang Huoqing , Su Xiaoyun
Published: April 2022

Xylanase releases xylo-oligosaccharides from dietary xylan, which stimulate the growth of the gut bacteria lactobacilli. Many lactobacilli adhere to dietary fibers, which may facilitate the assimilation of xylo-oligosaccharides and help them gain competence in the gut, but the underlying mechanisms remain elusive. Herein we report, from the highly abundant transcripts of Lactobacillus brevis cultured in wheat arabinoxylan supplemented with a xylanase, the identification of genes encoding four putative cell-surface WxL proteins (Lb630, Lb631, Lb632, and Lb635) and one S-layer protein (Lb1325) with either cellulose- or xylan-binding ability. The repetitively occurring WxL proteins were encoded by a gene cluster, among which Lb630 was chosen for further mutational studies. The analysis revealed three aromatic residues (F30, W61, and W156) that might be involved in the interaction of the protein with cellulose. A homology search in the genome of Enterococcus faecium identified three WxL proteins with conserved counterparts of these three aromatic residues, and they were also found to be able to bind cellulose and xylan. The findings suggested a role of the cell-surface WxL and S-layer proteins in assisting the cellular adhesion of L. brevis to plant cell wall polysaccharides.
Decoding the Synaptic Proteome with Long-Term Exposure to Midazolam during Early Development
Authors: Nguyen Nghi M. , Vellichirammal Neetha N. , Guda Chittibabu , Pendyala Gurudutt
Published: April 2022

The intensive use of anesthetic and sedative agents in the neonatal intensive care unit (NICU) has raised controversial concerns about the potential neurodevelopmental risks. This study focused on midazolam (MDZ), a common benzodiazepine regularly used as a sedative on neonates in the NICU. Mounting evidence suggests a single exposure to MDZ during the neonatal period leads to learning disturbances. However, a knowledge gap that remains is how long-term exposure to MDZ during very early stages of life impacts synaptic alterations. Using a preclinical rodent model system, we mimicked a dose-escalation regimen on postnatal day 3 (P3) pups until day 21. Next, purified synaptosomes from P21 control and MDZ animals were subjected to quantitative mass-spectrometry-based proteomics, to identify potential proteomic signatures. Further analysis by ClueGO identified enrichment of proteins associated with actin-binding and protein depolymerization process. One potential hit identified was alpha adducin (ADD1), belonging to the family of cytoskeleton proteins, which was upregulated in the MDZ group and whose expression was further validated by Western blot. In summary, this study sheds new information on the long-term exposure of MDZ during the early stages of development impacts synaptic function, which could subsequently perturb neurobehavioral outcomes at later stages of life.
Methylglyoxal Impairs Sister Chromatid Separation in Lymphocytes
Authors: Donnellan Leigh , Young Clifford , Simpson Bradley S. , Dhillon Varinderpal S. , Costabile Maurizio , Hoffmann Peter , Fenech Michael , Deo Permal
Published: April 2022

The accurate segregation of sister chromatids is complex, and errors that arise throughout this process can drive chromosomal instability and tumorigenesis. We recently showed that methylglyoxal (MGO), a glycolytic by-product, can cause chromosome missegregation events in lymphocytes. However, the underlying mechanisms of this were not explored. Therefore, in this study, we utilised shotgun proteomics to identify MGO-modified proteins, and label-free quantitation to measure changes in protein abundance following exposure to MGO. We identified numerous mitotic proteins that were modified by MGO, including those involved in the separation and cohesion of sister chromatids. Furthermore, the protein abundance of Securin, an inhibitor of sister chromatid separation, was increased following treatment with MGO. Cytological examination of chromosome spreads showed MGO prevented sister chromatid separation, which was associated with the formation of complex nuclear anomalies. Therefore, results from this study suggest MGO may drive chromosomal instability by preventing sister chromatid separation.
Fatty Acids and Metabolomic Composition of Follicular Fluid Collected from Environments Associated with Good and Poor Oocyte Competence in Goats
Authors: Izquierdo Dolors , Roura Montserrat , Pérez-Trujillo Míriam , Soto-Heras Sandra , Paramio María-Teresa
Published: April 2022

In goats, embryo oocyte competence is affected by follicle size regardless the age of the females. In previous studies we have found differences in blastocyst development between oocytes coming of small (<3 mm) and large follicles (>3 mm) in prepubertal (1–2 months-old) goats. Oocyte competence and Follicular Fluid (FF) composition changes throughout follicle growth. The aim of this study was to analyze Fatty Acids (FAs) composition and metabolomic profiles of FF recovered from small and large follicles of prepubertal goats and follicles of adult goats. FAs were analyzed by chromatography and metabolites by 1H-Nuclear Magnetic Resonance (1H-NMR) Spectrometry. The results showed important differences between adult and prepubertal follicles: (a) the presence of α,β-glucose in adult and no detection in prepubertal; (b) lactate, -N-(CH3)3 groups and inositol were higher in prepubertal (c) the percentage of Linolenic Acid, Total Saturated Fatty Acids and n-3 PUFAs were higher in adults; and (d) the percentage of Linoleic Acid, total MUFAs, PUFAs, n-6 PUFAs and n-6 PUFAs: n-3 PUFAs ratio were higher in prepubertal goats. Not significant differences were found in follicle size of prepubertal goats, despite the differences in oocyte competence for in vitro embryo production.
Genome Integrity and Neurological Disease
Authors: Scheijen Elle E. M. , Wilson David M.
Published: April 2022

Neurological complications directly impact the lives of hundreds of millions of people worldwide. While the precise molecular mechanisms that underlie neuronal cell loss remain under debate, evidence indicates that the accumulation of genomic DNA damage and consequent cellular responses can promote apoptosis and neurodegenerative disease. This idea is supported by the fact that individuals who harbor pathogenic mutations in DNA damage response genes experience profound neuropathological manifestations. The review article here provides a general overview of the nervous system, the threats to DNA stability, and the mechanisms that protect genomic integrity while highlighting the connections of DNA repair defects to neurological disease. The information presented should serve as a prelude to the Special Issue “Genome Stability and Neurological Disease”, where experts discuss the role of DNA repair in preserving central nervous system function in greater depth.
High eEF1A1 Protein Levels Mark Aggressive Prostate Cancers and the In Vitro Targeting of eEF1A1 Reveals the eEF1A1–actin Complex as a New Potential Target for Therapy
Authors: Bosutti Alessandra , Dapas Barbara , Grassi Gabriele , Bussani Rossana , Zanconati Fabrizio , Giudici Fabiola , Bottin Cristina , Pavan Nicola , Trombetta Carlo , Scaggiante Bruna
Published: April 2022

Although the eukaryotic elongation factor eEF1A1 plays a role in various tumours, there is little information on its prognosis/therapeutic value in prostate carcinoma. In high-grade and castration-resistant prostate carcinoma (CRPC), the identification of novel therapeutic markers/targets remains a priority. The expression of eEF1A1 protein was determined in formalin-fixed, paraffin-embedded prostate cancer and hyperplasia tissue by IHC. The role of eEF1A1 was investigated in a cellular model using a DNA aptamer (GT75) we previously developed. We used the aggressive CRPC cancer PC-3 and non-tumourigenic PZHPV-7 lines. Cytotoxicity was measured by the MTS assay and eEF1A1 protein levels by in-cell Western assays. The mRNA levels of eEF1A1 were measured by qPCR and ddPCR. Higher expression of eEF1A1 was found in Gleason 7–8 compared with 4–6 tissues (Gleason ≥ 7, 87% versus Gleason ≤ 6, 54%; p = 0.033). Patients with a high expression of eEF1A1 had a worse clinical outcome. In PC-3, but not in PZHPV-7, GT75 decreased cell viability and increased autophagy and cell detachment. In PC-3 cells, but not in PZHPV-7, GT75 mainly co-localised with the fraction of eEF1A1 bound to actin. Overexpression of the eEF1A1 protein can identify aggressive forms of prostate cancer. The targeting of eEF1A1 by GT75 impaired cell viability in PC-3 cancer cells but not in PZHPV-7 non-tumourigenic cells, indicating a specific role for the protein in cancer survival. The eEF1A1–actin complexes appear to be critical for the viability of PC-3 cancer cells, suggesting that eEF1A1 may be an attractive target for therapeutic strategies in advanced forms of prostate cancer.
Short- and Long-Term Mortalities of Small and Large Larvae of Alphitobius diaperinus (Panzer) (Coleoptera: Tenebrionidae) on Concrete Surfaces Treated with Three Insecticides: Impact of Food
Authors: Kavallieratos Nickolas G. , Nika Erifili P. , Skourti Anna , Filintas Constantin S. , Goumenou Theofania D.
Published: April 2022

The lesser mealworm, Alphitobius diaperinus (Panzer) (Coleoptera: Tenebrionidae) is an important stored-product pest for the poultry industry as it is a vector of dangerous pathogens for humans. In the present study, we evaluated the short- and long-term mortalities of small and large larvae of A. diaperinus when they were exposed to concrete-covered Petri dishes treated with etofenprox, deltamethrin, and the combination of piperonyl butoxide+acetamiprid+d-tetramethrin. Small and large larvae were exposed to each insecticide applied on concrete surfaces with or without food. The short-term mortality was recorded after 1 day, 3 days, 5 days, and 7 days, while the long-term mortality was recorded 7 days after the transport of the larvae alive to pesticide-free concrete-covered dishes. Regarding short-term mortality levels, 97.8% and 80.0% of the small and large larvae, that were exposed to etofenprox without food, died after 7 days of exposure, respectively. Concerning deltamethrin, all tested small larvae were killed after 3 days (without food) and 5 days (with food) of exposure. For large larvae, deltamethrin caused 98.9% (with food) and 100.0% (without food) mortality levels after 5 days of exposure. The combination of piperonyl butoxide+acetamiprid+d-tetramethrin caused high mortality levels to small larvae, i.e., 84.4% and 100.0% on dishes with and without food, respectively, but low to moderate mortality levels to large larvae that did not exceed 67.8% after 7 days of exposure. Long-term mortality varied vastly among the tested insecticides. Etofenprox killed 100.0% of the small larvae on concrete without food, but 24.0% of the large larvae exposed to concrete containing food. Deltamethrin did not provide long-term mortality to large larvae when food was present. Piperonyl butoxide+acetamiprid+d-tetramethrin caused mortality rates that overall varied from 33.5% (large larvae on concrete with food) to 85.0% (small larvae on concrete with food). In conclusion, deltamethrin killed almost all exposed larvae at exposures of ≤5 days, regardless of their size and the presence of food on the concrete.