bluuebunny/crossref_metadata_2025 huggingface dataset:
Haptic Glove Systems in Combination with Semi-Immersive Virtual Reality for Upper Extremity Motor Rehabilitation after Stroke: A Systematic Review and Meta-Analysis
Authors: Fernández-Vázquez Diego , Cano-de-la-Cuerda Roberto , Navarro-López Víctor
Published: August 2022

Background: The effectiveness of the virtual reality (VR) for the upper extremity (UE) motor rehabilitation after stroke has been widely studied. However, the effectiveness of the combination between rehabilitation gloves and semi-immersive VR (SVR) compared to conventional treatment has not yet been studied. Methods: A systematic search was conducted in Pubmed, Web of Science, PEDRo, and Scopus, Cochrane, CINHAAL databases from inception to May 2022. Randomized controlled trials were included if patients were under rehabilitation with haptic gloves combined with SVR intervention focused on the UE rehabilitation in stroke patients. Risk of bias and methodological quality were evaluated with the Physiotherapy Evidence Database (PEDro), and the modified Cochrane library criteria. A random effects model was used for the quantitative assessment of the included studies using the standard mean difference with a 95% confidence interval. Heterogeneity among the included studies was assessed using Cochran’s Q test and the incoherence index (I2). Results: After a first screening, seven studies were included. Significant differences with a 95% confidence interval were obtained in favor of the rehabilitation glove combined with SVR in the short term (SMD—standardized mean differences = 0.38, 95% CI—confidence interval = 0.20; 0.56; Z: 4.24; p =< 0.001). In the long term, only the studies that performed an intervention based in rehabilitation glove combined with SVR with also included rehabilitation were able to maintain the improvements (SMD = 0.71, 95% CI = 0.40; 1.02; Z: 4.48; p =< 0.001). Conclusions: The combined use of rehabilitation haptic gloves and SVR with conventional rehabilitation produces significant improvements with respect to conventional rehabilitation treatment alone in terms of functionality of the UE in stroke patients.
Parental Divorce Process and Post-Divorce Parental Behaviors and Strategies: Examining Emerging Adult Children’s Attachment-Related Anxiety and Avoidance
Authors: Smith-Etxeberria Klara , Corres-Medrano Irune , Fernandez-Villanueva Itziar
Published: August 2022

The main goal of this study was to examine the role of parental behaviors during both the process of divorce and the post-divorce period on emerging adult children’s attachment-related anxiety and avoidance. Specifically, we analyzed how recalled coparental respect and cooperation, interparental conflict, positive parenting strategies, and both parents’ emotional state and instability from adult children’s perspective during the divorce process and the post-divorce period were associated with emerging adult children’s current attachment representations. Our sample consisted of 173 emerging adults (Mage = 22.01). The results of this study demonstrate that paternal coparental respect and cooperation along with freedom provided by the mother to talk about the father during the divorce process and post-divorce period were both related to lower attachment-related avoidance. Our findings also confirm a significant link between some paternal positive attitudes during the divorce process (i.e., freedom provided by the father to talk about the mother) and low attachment-related anxiety. Overall, the results of this research confirm that beyond divorce perse, several variables surrounding the divorce process better explain variations in adult children’s attachment representations, which contribute to better comprehending the effects of parental divorce.
Conceptual Design of the “Private Car” Self-Isolation Ecosystem for the 2019-nCoV Infection
Authors: Wang Yudong , Wang Lanting , Wu Xinggui , Ding Ziyi , Zheng Wanbo , Liang Xingxing , An Huaming
Published: August 2022

Since the beginning of the COVID-19 outbreak, confirmed and suspected cases of the disease have been increasing rapidly. The isolation of cases is one of the most effective methods for the control and containment of COVID-19 and has been rapidly popularized. Problems with isolation have gradually emerged, such as the inadequate allocation of isolation resources and the failure to properly resettle many of the suspected cases of the 2019-nCoV infection. In this paper, a self-isolation ecosystem of a rapid-deploying negative-pressurized “private car” is proposed for housing patients with 2019-nCoV infection, which could be lightweight, moderately sized and transparent to enable group supervision and communication. This “private car” isolation method aims to achieve self-isolation of patients and essentially solves the problem of where and how to isolate suspected cases while saving isolation resources and preventing the large-scale transmission of COVID-19.
Analysis of Factors Associated with Subjective Mild Cognitive Impairment (MCI) among Older Adults Resident in the Community
Authors: Hwang Eun Jeong
Published: August 2022

This study explored the associated factors of mild cognitive impairment (MCI) in older adults, focusing on personal characteristics and health promotion activities. The research design of this study was a non-experimental, cross-sectional design. This study used secondary data from the 2019 community health survey conducted by the Korea Disease Control and Prevention Agency (KDCA). In this study, 20,041 older adults with subjective MCI and 52,587 healthy older adults—a total of 72,628 subjects—were analyzed as the final subjects in this study. The data were analyzed by using descriptive statistics, a chi-square test, an independent t-test, and logistic regression. The results indicate that the probability of experiencing subjective MCI significantly decreased with an increase in monthly income (odds ratio (OR) = 1.71, 95% confidence interval (CI) = 1.19–2.46); increased with an increase in depressive symptoms (odds ratio (OR) = 1.09, 95% confidence interval (CI) = 1.04–1.15); and decreased with an increase in the quality of life level (OR = 0.90, 95% CI = 0.82–0.99). Through the results of this study, several factors related to MCI in older adults were identified. If these related factors are properly managed, the possibility of MCI in older adults may be reduced. Therefore, MCI in older adults should be addressed as a preventable disease rather than a natural aging process.
Heat Wave and Bushfire Meteorology in New South Wales, Australia: Air Quality and Health Impacts
Authors: Islam Mohammad S. , Fang Tianxin , Oldfield Callum , Larpruenrudee Puchanee , Beni Hamidreza Mortazavy , Rahman Md. M. , Husain Shahid , Gu Yuantong
Published: August 2022

The depletion of air quality is a major problem that is faced around the globe. In Australia, the pollutants emitted by bushfires play an important role in making the air polluted. These pollutants in the air result in many adverse impacts on the environment. This paper analysed the air pollution from the bushfires from November 2019 to July 2020 and identified how it affects the human respiratory system. The bush fires burnt over 13 million hectares, destroying over 2400 buildings. While these immediate effects were devastating, the long-term effects were just as devastating, with air pollution causing thousands of people to be admitted to hospitals and emergency departments because of respiratory complications. The pollutant that caused most of the health effects throughout Australia was Particulate Matter (PM) PM2.5 and PM10. Data collection and analysis were covered in this paper to illustrate where and when PM2.5 and PM10, and other pollutants were at their most concerning levels. Susceptible areas were identified by analysing environmental factors such as temperature and wind speed. The study identified how these pollutants in the air vary from region to region in the same time interval. This study also focused on how these pollutant distributions vary according to the temperature, which helps to determine the relationship between the heatwave and air quality. A computational model for PM2.5 aerosol transport to the realistic airways was also developed to understand the bushfire exhaust aerosol transport and deposition in airways. This study would improve the knowledge of the heat wave and bushfire meteorology and corresponding respiratory health impacts.
Application of an EMG-Rehabilitation Robot in Patients with Post-Coronavirus Fatigue Syndrome (COVID-19)—A Feasibility Study
Authors: Zasadzka Ewa , Tobis Sławomir , Trzmiel Tomasz , Marchewka Renata , Kozak Dominika , Roksela Anna , Pieczyńska Anna , Hojan Katarzyna
Published: August 2022

This pilot study aimed to assess the safety and feasibility of an EMG-driven rehabilitation robot in patients with Post-Viral Fatigue (PVF) syndrome after COVID-19. The participants were randomly assigned to two groups (IG—intervention group and CG—control group) in an inpatient neurological rehabilitation unit. Both groups were assessed on admission and after six weeks of rehabilitation. Rehabilitation was carried out six days a week for six weeks. The patients in the IG performed additional training using an EMG rehabilitation robot. Muscle fatigue was assessed using an EMG rehabilitation robot; secondary outcomes were changes in hand grip strength, Fatigue Assessment Scale, and functional assessment scales (Functional Independence Measure, Barthel Index). Both groups improved in terms of the majority of measured parameters comparing pre- and post-intervention results, except muscle fatigue. Muscle fatigue scores presented non-significant improvement in the IG and non-significant deterioration in the CG. Using an EMG rehabilitation robot in patients with PVF can be feasible and safe. To ascertain the effectiveness of such interventions, more studies are needed, particularly involving a larger sample and also assessing the participants’ cognitive performance.
Chances of Mortality Are 3.5-Times Greater in Elderly Patients with Umbilical Hernia Than in Adult Patients: An Analysis of 21,242 Patients
Authors: Patel Saral , Smiley Abbas , Feingold Cailan , Khandehroo Bardia , Kajmolli Agon , Latifi Rifat
Published: August 2022

The goal of this study was to identify risk factors that are associated with mortality in adult and elderly patients who were hospitalized for umbilical hernia. A total of 14,752 adult patients (ages 18–64 years) and 6490 elderly patients (ages 65+), who were admitted emergently for umbilical hernia, were included in this retrospective cohort study. The data were gathered from the National Inpatient Sample (NIS) 2005–2014 database. Predictors of mortality were identified via a multivariable logistic regression, in patients who underwent surgery and those who did not for adult and elderly age groups. The mean (SD) ages for adult males and females were 48.95 (9.61) and 46.59 (11.35) years, respectively. The mean (SD) ages for elderly males and females were 73.62 (6.83) and 77.31 (7.98) years, respectively. The overall mortality was low (113 or 0.8%) in the adult group and in the elderly group (179 or 2.8%). In adult patients who underwent operation, age (OR = 1.066, 95% CI: 1.040–1.093, p < 0.001) and gangrene (OR = 5.635, 95% CI: 2.288–13.874, p < 0.001) were the main risk factors associated with mortality. Within the same population, female sex was found to be a protective factor (OR = 0.547, 95% CI: 0.351–0.854, p = 0.008). Of the total adult sample, 43% used private insurance, while only 18% of patients in the deceased population used private insurance. Conversely, within the entire adult population, only about 48% of patients used Medicare, Medicaid, or self-pay, while these patients made up 75% of the deceased group. In the elderly surgical group, the main risk factors significantly associated with mortality were frailty (OR = 1.284, 95% CI: 1.105–1.491, p = 0.001), gangrene (OR = 13.914, 95% CI: 5.074–38.154, p < 0.001), and age (OR = 1.034, 95% CI: 1.011–1.057, p = 0.003). In the adult non-operation group, hospital length of stay (HLOS) was a significant risk factor associated with mortality (OR = 1.077, 95% CI: 1.004–1.155, p = 0.038). In the elderly non-operation group, obstruction was the main risk factor (OR = 4.534, 95% CI: 1.387–14.819, p = 0.012). Elderly patients experienced a 3.5-fold higher mortality than adult patients who were emergently admitted with umbilical hernia. Increasing age was a significant risk factor of mortality within all patient populations. In the adult surgical group, gangrene, Medicare, Medicaid, and self-pay were significant risk factors of mortality and female sex was a significant protective factor. In the adult non-surgical group, HLOS was the main risk factor of mortality. In the elderly population, frailty and gangrene were the main risk factors of mortality within the surgical group, and obstruction was the main risk factor for the non-surgical group.
Effects of Tartrazine on Some Sexual Maturation Parameters in Immature Female Wistar Rats
Authors: Mindang Elisabeth Louise Ndjengue , Awounfack Charline Florence , Ndinteh Derek Tantoh , Krause Rui W. M. , Njamen Dieudonne
Published: August 2022

Over the past century, the average age for onset of puberty has declined. Several additives present in our food are thought to contribute significantly to this early puberty which is recognized to also affect people’s health in later life. On this basis, the impact of 40-days unique oral administration of the food dye tartrazine (7.5, 27, and 47 mg/kg BW doses) was evaluated on some sexual maturation parameters on immature female Wistar rats. Vaginal opening was evaluated during the treatment period. At the end of the treatments, animals were sacrificed (estrus phase) and the relative weight of reproductive organs, pituitary gonadotrophin and sexual steroids level, cholesterol level in ovaries and folliculogenesis were evaluated. Compared to the control group, animals receiving tartrazine (47 mg/kg BW) showed significantly high percentage of early vaginal opening from day 45 of age, and an increase in the number of totals, primaries, secondaries, and antral follicles; a significant increase in serum estrogen, LH and in uterine epithelial thickness. Our findings suggest that tartrazine considerably disturbs the normal courses of puberty. These results could validate at least in part the global observations on increasingly precocious puberty in girls feeding increasingly with industrially processed foods.
Does Childhood Maltreatment Predict Moral Disgust? The Underlying Mediating Mechanisms
Authors: Zhang Qingji , Zhou Yue , Chen Ziyuan , Xiang Yanhui
Published: August 2022

Although moral disgust is one of the most important moral emotions, there is limited evidence about the antecedents of it in China. This paper aimed to discuss the linkage between childhood maltreatment and moral disgust, and investigated the specific mechanism between these two variables from the perspective of emotional development and moral development, respectively, based on the Tripartite Model. By combining random sampling and cluster sampling, this study recruited 968 participants from college. Then, childhood maltreatment, moral disgust, emotional intelligence, and empathy were measured separately by using the Childhood Trauma Questionnaire (CTQ), Moral Disgust Scale (MD), Wong Law Emotional Intelligence Scale (WLEIS), and Interpersonal Reactivity Index–C (IRI). Additionally, the results of the mediation model analysis show that childhood maltreatment is negatively predictable of moral disgust. In addition, the mechanism by which childhood maltreatment influences moral disgust could be explained by the effect of emotional intelligence on empathy. To sum up, this study explored and explained the specific mechanism between childhood maltreatment and moral disgust, replenishing previous achievements and providing support for the design of intervention on moral disgust by improving emotional intelligence and empathy.
Physical Activity and Quality of Life in Adult Men and Women with Distorted Perception of Weight Status: Nationwide Surveys (KNHANES 2016–2018)
Authors: Lee Su-Jin , Lim Min-Gyu , Kim Jung hee , Park Chulyong , Ko YoungJi , Kim Myung-Gwan , Kim Chul-Hyun , Kim Aeryoung , Hwang Jong-Moon
Published: August 2022

This study analyzed the distorted perception of weight in adults aged 20 years or older and investigated the difference in the amount of physical activity and health-related quality of life (HRQOL). This study examined 21,326 adults regarding their body mass index (BMI), subjective body recognition (SBR), physical activity (according to the Global Physical Activity Questionnaire; GPAQ), and HRQOL (EuroQol-5 Dimension; EQ-5D) from the 7th Korea National Health and Nutrition Examination Survey (2016–2018). Independent t-test, analysis of variance (ANOVA), chi-square test, and multiple regression analysis were conducted. The group with the same BMI and SBR significantly showed a long time of activity vigorous-intensity (F = 21.25, p = 0.003) and moderate-intensity time (F = 17.24, p < 0.001). In the ‘BMI = SBR’ group, the sub-group with normal BMI and normal SBR showed the highest vigorous-intensity (mean ± SD = 7.20 ± 26.05, F = 37.86, p < 0.001) and moderate-intensity (mean ± SD = 13.89 ± 30.18, F = 43.27, p < 0.001) activity times. The sub-group with normal BMI and normal SBR had the highest percentage of responding as normal in the five EQ-5D sub-items. For the score of the EQ-5D Index, the highest score was shown in the group that felt subjectively more obese than the actual BMI (F = 56.83, p < 0.001). In the ‘BMI = SBR’ group, these factors related to physical activity (vigorous-intensity, moderated-intensity, and walking) are factors influencing health-related quality of life in this regression model (F = 396.57, p < 0.001, R2 = 0.165). Various health promotion programs and policy recommendations to reduce the distorted perception of weight are required.
Pathogen Profile of Children Hospitalised with Severe Acute Respiratory Infections during COVID-19 Pandemic in the Free State Province, South Africa
Authors: Ogunbayo Ayodeji E. , Mogotsi Milton T. , Sondlane Hlengiwe , Nkwadipo Kelebogile R. , Sabiu Saheed , Nyaga Martin M.
Published: August 2022

Severe acute respiratory infections (SARI) contribute to mortality in children ≤5 years. Their microbiological aetiologies are often unknown and may be exacerbated in light of coronavirus disease 19 (COVID-19). This study reports on respiratory pathogens in children ≤5 years (n = 84) admitted with SARI during and between the second and third waves of COVID-19 infection in South Africa. Nasopharyngeal/oropharyngeal swabs collected were subjected to viral detection using QIAstat-Dx® Respiratory SARS-CoV-2 Panel. The results revealed viral positivity and negativity detection rates of 88% (74/84) and 12% (10/84), respectively. Of the 21 targeted pathogens, human rhinovirus/enterovirus (30%), respiratory syncytial virus (RSV; 26%), and severe acute respiratory syndrome coronavirus 2 (24%) were mostly detected, with other viruses being 20% and a co-infection rate of 64.2% (54/84). Generally, RSV-positive samples had lower Ct values, and fewer viruses were detected during the third wave. Changes in the circulation patterns of respiratory viruses with total absence of influenza virus could be attributed to measures against COVID-19 transmission, which may result in waned immunity, thereby increasing susceptibility to severe infections in the following season. High viral co-infection rate, as detected, may complicate diagnosis. Nonetheless, accurate identification of the pathogens may guide treatment decisions and infection control.
The Sources and Potential Hosts Identification of Antibiotic Resistance Genes in the Yellow River, Revealed by Metagenomic Analysis
Authors: Zhang Kai , Li Kuangjia , Liu Ziyi , Li Qidi , Li Wenpeng , Chen Qi , Xia Yangchun , Hu Feiyue , Yang Fengxia
Published: August 2022

The fate of antibiotic resistance genes (ARGs) has been revealed in various environmental media in recent years. Namely, the emergence of genes that resist colistin and carbapenems has attracted wide attention. However, the pollution condition of ARGs and sources in the Yellow River is still little understood, despite the river being the second longest in China. The present study determined the levels of ARG pollution in the Henan section of the Yellow River and evaluated the role of the aquaculture industry in the spread of ARGs. As revealed by the results, a total of 9 types of ARGs were detected in the sediments of the Yellow River, and the total ARG content in the Yellow River ranges from 7.27 to 245.45 RPKM. Sul1 and sul2 are the dominant ARGs, and the huge usage of sulfonamides, horizontal gene transfer, and wide bacteria host contribute to the prevalence of these two genes. The results of Spearman correlation analysis indicate that the breeding industry has little influence on ARGs in the Yellow River. Network analysis reveals that the opportunistic pathogen Pseudomonas is the potential host of sul1, tetG, and ANT(3′′)-IIa, which can pose a risk to human health.
Modelling the Mobility Changes Caused by Perceived Risk and Policy Efficiency
Authors: Wu Sijin , Grant-Muller Susan , Yang Lili
Published: August 2022

In many countries, governments have implemented non-pharmaceutical techniques to limit COVID-19 transmission. Restricting human mobility is one of the most common interventions, including lockdown, travel restrictions, working from home, etc. However, due to the strong transmission ability of the virus variants, further rounds of interventions, including a strict lockdown, are not considered as effective as expected. The paper aims to understand how the lockdown policy and pandemics changed human mobility in the real scenario. Here we focus on understanding the mobility changes caused by compliance with restrictions and risk perceptions, using a mobility index from the Google report during three strict lockdown periods in Leeds, the largest city in the county of West Yorkshire, England, from March 2020 to March 2021. The research uses time-varying z-scores and Principal Component Analysis (PCA) to simulate how local people dynamically process and perceive health risks based on multi-dimensional daily COVID-19 reports first. Further modelling highlights exponentially increasing policy non-compliance through the duration of lockdown, probably attributable to factors such as mental anxiety and economic pressures. Finally, the proposed nonlinear regression model examines the mobility changes caused by the population’s dynamic risk perceptions and lockdown duration. The case study model in Leeds shows a good fit to the empirical mobility data and indicates that the third lockdown policy took effect much slower than the first. At the same time, the negative impact of the epidemic on population mobility decayed by 40% in the third lockdown period in contrast with the first lockdown. The risk perception estimation methods could reflect that the local population became increasingly accustomed to the COVID-19 situation, and local people rationally evaluated the risks of COVID in the third lockdown period. The results demonstrate that simulated risk perceptions and policy decay could explain urban mobility behaviour during lockdown periods, which could be a reference for future decision-making processes.
Spatial Pattern and Formation Mechanism of Rural Tourism Resources in China: Evidence from 1470 National Leisure Villages
Authors: Xie Yuchen , Meng Xiangzhuang , Cenci Jeremy , Zhang Jiazhen
Published: August 2022

Rural tourism development has been an essential driving force behind China’s promotion of integrated urban–rural development, sustainable rural development and rural revitalization in the new era. This study included 1470 villages on the national list of beautiful leisure villages in China (BLVCs) from 2010 to 2021. We explored the distribution characteristics and influencing factors based on mathematical statistics and spatial analysis in ArcGIS to provide a theoretical reference for promoting the development of leisure village agriculture and rural tourism. The results show that the distribution of BLVC presents a clustered state, showing a distribution pattern of a dual core, seven centers and multiple scattered points. BLVCs are mainly distributed in areas with flat terrain and sufficient water resources, which are conducive to agricultural production and life. Having convenient transportation and rich tourism resources aids the promotion of rural tourism development. The resulting gap in regional development is balanced to some extent by government support. The research results provide a reference value for future rural spatial optimization and sustainable development. This paper summarizes the law of rural development and clarifies the factors influencing the development of rural tourism, and it provides the Chinese experience as a model for a rural renaissance empowered by rural tourism.
Identification of Urban Agglomeration Spatial Range Based on Social and Remote-Sensing Data—For Evaluating Development Level of Urban Agglomeration
Authors: Zhang Shuai , Wei Hua
Published: August 2022

The accurate identification of urban agglomeration spatial area is helpful in understanding the internal spatial relationship under urban expansion and in evaluating the development level of urban agglomeration. Previous studies on the identification of spatial areas often ignore the functional distribution and development of urban agglomerations by only using nighttime light data (NTL). In this study, a new method is firstly proposed to identify the accurate spatial area of urban agglomerations by fusing night light data (NTL) and point of interest data (POI); then an object-oriented method is used by this study to identify the spatial area, finally the identification results obtained by different data are verified. The results show that the accuracy identified by NTL data is 82.90% with the Kappa coefficient of 0.6563, the accuracy identified by POI data is 81.90% with the Kappa coefficient of 0.6441, and the accuracy after data fusion is 90.70%, with the Kappa coefficient of 0.8123. The fusion of these two kinds of data has higher accuracy in identifying the spatial area of urban agglomeration, which can play a more important role in evaluating the development level of urban agglomeration; this study proposes a feasible method and path for urban agglomeration spatial area identification, which is not only helpful to optimize the spatial structure of urban agglomeration, but also to formulate the spatial development policy of urban agglomeration.
Antioxidant Therapeutic Strategies in Neurodegenerative Diseases
Authors: Morén Constanza , deSouza Ruth Mary , Giraldo Darly Milena , Uff Christopher
Published: August 2022

The distinguishing pathogenic features of neurodegenerative diseases include mitochondrial dysfunction and derived reactive oxygen species generation. The neural tissue is highly sensitive to oxidative stress and this is a prominent factor in both chronic and acute neurodegeneration. Based on this, therapeutic strategies using antioxidant molecules towards redox equilibrium have been widely used for the treatment of several brain pathologies. Globally, polyphenols, carotenes and vitamins are among the most typical exogenous antioxidant agents that have been tested in neurodegeneration as adjunctive therapies. However, other types of antioxidants, including hormones, such as the widely used melatonin, are also considered neuroprotective agents and have been used in different neurodegenerative contexts. This review highlights the most relevant mitochondrial antioxidant targets in the main neurodegenerative disorders including Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease and also in the less represented amyotrophic lateral sclerosis, as well as traumatic brain injury, while summarizing the latest randomized placebo-controlled trials.
Sorafenib and Doxorubicin Show Synergistic Effects in Human and Canine Osteosarcoma Cell Lines
Authors: Yang Ya-Ting , Yuzbasiyan-Gurkan Vilma
Published: August 2022

Osteosarcoma (OSA) is the most common bone tumor in both humans and dogs and has a nearly ten-fold higher incidence in dogs than humans. Despite advances in the treatment of other cancers, the overall survival rates for OSA have stagnated for the past four decades. Therefore, there is a great need to identify novel and effective treatments. We screened a series of tyrosine kinase inhibitors and selected sorafenib, a multi-kinase inhibitor, for further evaluation alone and in combination with cisplatin, carboplatin, and doxorubicin on canine and human OSA cell lines. Our data point to synergistic effects when sorafenib is combined with doxorubicin, but not when combined with cisplatin or carboplatin, in both human and canine OSA. Based on current findings, clinical trials using a combination of doxorubicin and sorafenib in proof-of-concept studies in dogs are warranted. These studies can be carried out relatively quickly in dogs where case load is high and, in turn, provide useful data for the initiation of clinical trials in humans.
Macrophage-Specific, Mafb-Deficient Mice Showed Delayed Skin Wound Healing
Authors: Inoue Yuri , Liao Ching-Wei , Tsunakawa Yuki , Tsai I-Lin , Takahashi Satoru , Hamada Michito
Published: August 2022

Macrophages play essential roles throughout the wound repair process. Nevertheless, mechanisms regulating the process are poorly understood. MAFB is specifically expressed in the macrophages in hematopoietic tissue and is vital to homeostatic function. Comparison of the skin wound repair rates in macrophage-specific, MAFB-deficient mice (Mafbf/f::LysM-Cre) and control mice (Mafbf/f) showed that wound healing was significantly delayed in the former. For wounded GFP knock-in mice with GFP inserts in the Mafb locus, flow cytometry revealed that their GFP-positive cells expressed macrophage markers. Thus, macrophages express Mafb at wound sites. Immunohistochemical (IHC) staining, proteome analysis, and RT-qPCR of the wound tissue showed relative downregulation of Arg1, Ccl12, and Ccl2 in Mafbf/f::LysM-Cre mice. The aforementioned genes were also downregulated in the bone marrow-derived, M2-type macrophages of Mafbf/f::LysM-Cre mice. Published single-cell RNA-Seq analyses showed that Arg1, Ccl2, Ccl12, and Il-10 were expressed in distinct populations of MAFB-expressing cells. Hence, the MAFB-expressing macrophage population is heterogeneous. MAFB plays the vital role of regulating multiple genes implicated in wound healing, which suggests that MAFB is a potential therapeutic target in wound healing.
Identification of a Novel Lipase with AHSMG Pentapeptide in Hypocreales and Glomerellales Filamentous Fungi
Authors: Gutiérrez-Domínguez Denise Esther , Chí-Manzanero Bartolomé , Rodríguez-Argüello María Mercedes , Todd Jewel Nicole Anna , Islas-Flores Ignacio , Canseco-Pérez Miguel Ángel , Canto-Canché Blondy
Published: August 2022

Lipases are enzymes that hydrolyze triglycerides to fatty acids and glycerol. A typical element in lipases is a conserved motif of five amino acids (the pentapeptide), most commonly G-X-S-X-G. Lipases with the pentapeptide A-X-S-X-G are present in species of Bacillus, Paucimonas lemoignei, and the yeast Trichosporon asahii; they are usually thermotolerant and solvent resistant. Recently, while searching for true lipases in the Trichoderma harzianum genome, one lipase containing the pentapeptide AHSMG was identified. In this study, we cloned from T. harzianum strain B13-1 the lipase ID135964, renamed here as ThaL, which is 97.65% identical with the reference. We found that ThaL is a lid-containing true lipase of cluster III that belongs to a large family comprising highly conserved proteins in filamentous fungi in the orders Hypocreales and Glomerellales, in which predominantly pathogenic fungi are found. ThaL was expressed in conidia, as well as in T. harzianum mycelium, where it was cultured in liquid minimal medium. These results—together with the amino acid composition, absence of a signal peptide, mitochondrial sorting prediction, disordered regions in the protein, and lineage-specific phylogenetic distribution of its homologs—suggest that ThaL is a non-canonical effector. In summary, AHSMG-lipase is a novel lipase family in filamentous fungi, and is probably involved in pathogenicity.
Integrative Metabolome and Transcriptome Analysis Reveals the Regulatory Network of Flavonoid Biosynthesis in Response to MeJA in Camelliavietnamensis Huang
Authors: Yan Heqin , Zheng Wei , Wang Yong , Wu Yougen , Yu Jing , Xia Pengguo
Published: August 2022

Flavonoids are secondary metabolites widely found in plants, which perform various biological activities, such as antiinflammation, antioxidation, antitumor, and so on. Camellia vietnamensis Huang, a species of oil-tea Camellia tree, is an important woody oil crop species widely planted on Hainan Island, which provides health benefits with its high antioxidant activity and abundant flavonoid content. However, very little is known about the overall molecular mechanism of flavonoid biosynthesis in C. vietnamensis Huang. In this study, methyl jasmonate (MeJA) is used as an inducer to change the content of secondary metabolites in C. vietnamensis. Then, the potential mechanisms of flavonoid biosynthesis in C. vietnamensis leaves in response to MeJA were analyzed by metabolomics and transcriptomics (RNA sequencing). The results showed that metabolome analysis detected 104 flavonoids and 74 fatty acyls which showed different expression patterns (increased or decreased expression). It was discovered by KEGG analysis that three differentially accumulated metabolites (cinnamaldehyde, kaempferol and quercitrin) were annotated in the phenylpropanoid biosynthesis (ko00940), flavonoid biosynthesis (ko00941), and flavone and flavonol biosynthesis (ko00944) pathways. In the transcriptome analysis, 35 different genes involved in the synthesis of flavonoids were identified by MapMan analysis. The key genes (PAL, 4CL, CCR, CHI, CHS, C4H, FLS) that might be involved in the formation of flavonoid were highly expressed after 2 h of MeJA treatment. This study provides new insights and data supporting the molecular mechanism underlying the metabolism and synthesis of flavonoids in C. vietnamensis under MeJA treatment.
Identification of Potential Cytochrome P450 3A5 Inhibitors: An Extensive Virtual Screening through Molecular Docking, Negative Image-Based Screening, Machine Learning and Molecular Dynamics Simulation Studies
Authors: Islam Md Ataul , Dudekula Dawood Babu , Rallabandi V. P. Subramanyam , Srinivasan Sridhar , Natarajan Sathishkumar , Chung Hoyong , Park Junhyung
Published: August 2022

Cytochrome P450 3A5 (CYP3A5) is one of the crucial CYP family members and has already proven to be an important drug target for cardiovascular diseases. In the current study, the PubChem database was screened through molecular docking and high-affinity molecules were adopted for further assessment. A negative image-based (NIB) model was used for a similarity search by considering the complementary shape and electrostatics of the target and small molecules. Further, the molecules were segregated into active and inactive groups through six machine learning (ML) matrices. The active molecules found in each ML model were used for in silico pharmacokinetics and toxicity assessments. A total of five molecules followed the acceptable pharmacokinetics and toxicity profiles. Several potential binding interactions between the proposed molecules and CYP3A5 were observed. The dynamic behavior of the selected molecules in the CYP3A5 was explored through a molecular dynamics (MD) simulation study. Several parameters obtained from the MD simulation trajectory explained the stability of the protein–ligand complexes in dynamic states. The high binding affinity of each molecule was revealed by the binding free energy calculation through the MM-GBSA methods. Therefore, it can be concluded that the proposed molecules might be potential CYP3A5 molecules for therapeutic application in cardiovascular diseases subjected to in vitro/in vivo validations.
Forsythiaside A Improves the Inhibitory Efficiency of Recombinant Protein Vaccines against Bovine Viral Diarrhea Virus Infection
Authors: Yang Guanghui , Wang Jiufeng , Wang Shenghua , Zhu Yaohong
Published: August 2022

Bovine viral diarrhea virus (BVDV) is a critical animal pathogen that leads to cattle production losses associated with acute disease, immune dysregulation, reproductive failure, and respiratory disease. Due to the monotonous control technique and neglect of BVDV, increasing prevalence of BVDV has caused significant economic losses in the cattle industry worldwide. Therefore, novel anti-BVDV drugs are essential to prevent and control BVDV. Our previous studies have found that Forsythoside A (FTA) could inhibit the replication of BVDV via TRAF2-dependent CD28-4-1BB signaling in bovine peripheral blood mononuclear cells (PBMCs), but whether they can directly inhibit the BVDV remains unclear. Here, we further investigated the effects of FTA on BVDV and its underlying mechanisms of action. We found that FTA significantly inhibited the replication of BVDV in the MDBK cell directly. The results demonstrated that FTA could reduce the functional activation of Caspase-1 to inhibit the inflammatory response caused by BVDV infection and increase the expression of type I interferon (IFN-I) to clear the virus in vitro. The animal experiment was performed to evaluate the antiviral effect of FTA in vivo. Notably, after challenged with BVDV, mice with FTA + Erns-E2 protein displayed alleviated pathological damage and decreased the viral load in the spleen compared with mice inoculated with Erns-E2 protein. Furthermore, treatment with FTA enhanced body defense and delayed infection by the BVDV. Our results reveal that FTA suppresses BVDV replication both in vitro and in vivo and therefore shows promise as an anti-BVDV agent.
Functionalized Platinum Nanoparticles with Biomedical Applications
Authors: Gutiérrez de la Rosa Sagrario Yadira , Muñiz Diaz Ramiro , Villalobos Gutiérrez Paola Trinidad , Patakfalvi Rita , Gutiérrez Coronado Óscar
Published: August 2022

Functionalized platinum nanoparticles have been of considerable interest in recent research due to their properties and applications, among which they stand out as therapeutic agents. The functionalization of the surfaces of nanoparticles can overcome the limits of medicine by increasing selectivity and thereby reducing the side effects of conventional drugs. With the constant development of nanotechnology in the biomedical field, functionalized platinum nanoparticles have been used to diagnose and treat diseases such as cancer and infections caused by pathogens. This review reports on physical, chemical, and biological methods of obtaining platinum nanoparticles and the advantages and disadvantages of their synthesis. Additionally, applications in the biomedical field that can be utilized once the surfaces of nanoparticles have been functionalized with different bioactive molecules are discussed, among which antibodies, biodegradable polymers, and biomolecules stand out.
In Silico Study of Cell Surface Structures of Parabacteroides distasonis Involved in Its Maintenance within the Gut Microbiota
Authors: Chamarande Jordan , Cunat Lisiane , Alauzet Corentine , Cailliez-Grimal Catherine
Published: August 2022

The health-promoting Parabacteroides distasonis, which is part of the core microbiome, has recently received a lot of attention, showing beneficial properties for its host and potential as a new biotherapeutic product. However, no study has yet investigated the cell surface molecules and structures of P. distasonis that allow its maintenance within the gut microbiota. Moreover, although P. distasonis is strongly recognized as an intestinal commensal species with benefits for its host, several works displayed controversial results, showing it as an opportunistic pathogen. In this study, we reported gene clusters potentially involved in the synthesis of capsule, fimbriae-like and pili-like cell surface structures in 26 P. distasonis genomes and applied the new RfbA-typing classification in order to better understand and characterize the beneficial/pathogenic behavior related to P. distasonis strains. Two different types of fimbriae, three different types of pilus and up to fourteen capsular polysaccharide loci were identified over the 26 genomes studied. Moreover, the addition of data to the rfbA-type classification modified the outcome by rearranging rfbA genes and adding a fifth group to the classification. In conclusion, the strain variability in terms of external proteinaceous structure could explain the inter-strain differences previously observed of P. distasonis adhesion capacities and its potential pathogenicity, but no specific structure related to P. distasonis beneficial or detrimental activity was identified.
Nitrous Oxide Emissions from Nitrite Are Highly Dependent on Nitrate Reductase in the Microalga Chlamydomonas reinhardtii
Authors: Bellido-Pedraza Carmen M. , Calatrava Victoria , Llamas Angel , Fernandez Emilio , Sanz-Luque Emanuel , Galvan Aurora
Published: August 2022

Nitrous oxide (N2O) is a powerful greenhouse gas and an ozone-depleting compound whose synthesis and release have traditionally been ascribed to bacteria and fungi. Although plants and microalgae have been proposed as N2O producers in recent decades, the proteins involved in this process have been only recently unveiled. In the green microalga Chlamydomonas reinhardtii, flavodiiron proteins (FLVs) and cytochrome P450 (CYP55) are two nitric oxide (NO) reductases responsible for N2O synthesis in the chloroplast and mitochondria, respectively. However, the molecular mechanisms feeding these NO reductases are unknown. In this work, we use cavity ring-down spectroscopy to monitor N2O and CO2 in cultures of nitrite reductase mutants, which cannot grow on nitrate or nitrite and exhibit enhanced N2O emissions. We show that these mutants constitute a very useful tool to study the rates and kinetics of N2O release under different conditions and the metabolism of this greenhouse gas. Our results indicate that N2O production, which was higher in the light than in the dark, requires nitrate reductase as the major provider of NO as substrate. Finally, we show that the presence of nitrate reductase impacts CO2 emissions in both light and dark conditions, and we discuss the role of NO in the balance between CO2 fixation and release.
Cannabinoids and Chronic Liver Diseases
Authors: Mboumba Bouassa Ralph-Sydney , Sebastiani Giada , Di Marzo Vincenzo , Jenabian Mohammad-Ali , Costiniuk Cecilia T.
Published: August 2022

Nonalcoholic fatty liver disease (NAFLD), alcohol-induced liver disease (ALD), and viral hepatitis are the main causes of morbidity and mortality related to chronic liver diseases (CLDs) worldwide. New therapeutic approaches to prevent or reverse these liver disorders are thus emerging. Although their etiologies differ, these CLDs all have in common a significant dysregulation of liver metabolism that is closely linked to the perturbation of the hepatic endocannabinoid system (eCBS) and inflammatory pathways. Therefore, targeting the hepatic eCBS might have promising therapeutic potential to overcome CLDs. Experimental models of CLDs and observational studies in humans suggest that cannabis and its derivatives may exert hepatoprotective effects against CLDs through diverse pathways. However, these promising therapeutic benefits are not yet fully validated, as the few completed clinical trials on phytocannabinoids, which are thought to hold the most promising therapeutic potential (cannabidiol or tetrahydrocannabivarin), remained inconclusive. Therefore, expanding research on less studied phytocannabinoids and their derivatives, with a focus on their mode of action on liver metabolism, might provide promising advances in the development of new and original therapeutics for the management of CLDs, such as NAFLD, ALD, or even hepatitis C-induced liver disorders.
Vascular Reactions of the Diving Reflex in Men and Women Carrying Different ADRA1A Genotypes
Authors: Baranova Tatyana , Podyacheva Ekaterina , Zemlyanukhina Tatyana , Berlov Dmitrii , Danilova Maria , Glotov Oleg , Glotov Andrey
Published: August 2022

The diving reflex is an oxygen-saving mechanism which is accompanied by apnea, reflex bradycardia development, peripheral vasoconstriction, spleen erythrocyte release, and selective redistribution of blood flow to the organs most vulnerable to lack of oxygen, such as the brain, heart, and lungs. However, this is a poorly studied form of hypoxia, with a knowledge gap on physiological and biochemical adaptation mechanisms. The reflective sympathetic constriction of the resistive vessels is realized via ADRA1A. It has been shown that ADRA1A SNP (p.Arg347Cys; rs1048101) is associated with changes in tonus in vessel walls. Moreover, the Cys347 allele has been shown to regulate systolic blood pressure. The aim of this work was to evaluate whether the ADRA1A polymorphism affected the pulmonary vascular reactions in men and women in response to the diving reflex. Men (n = 52) and women (n = 50) untrained in diving aged 18 to 25 were recruited into the study. The vascular reactions and blood flow were examined by integrated rheography and rheography of the pulmonary artery. Peripheral blood circulation was registered by plethysmography. The ADRA1A gene polymorphism (p.Arg347Cys; rs1048101) was determined by PCR-RFLP. In both men and women, reflective pulmonary vasodilation did occur in response to the diving reflex, but in women this vasodilation was more pronounced and was accompanied by a higher filling of the lungs with blood.. Additionally, ADRA1A SNP (p.Arg347Cys; rs1048101) is associated with sex. Interestingly, women with the Arg347 allele demonstrated the highest vasodilation of the lung vessels. Therefore, our data may help to indicate women with the most prominent adaptive reactions to the diving reflex. Our data also indicate that women and men with the Cys allele of the ADRA1A gene polymorphism have the highest risk of developing lung hypertension in response to the diving reflex. The diving reflex is an oxygen-saving mechanism which is accompanied by apnea, reflex bradycardia development, peripheral vasoconstriction, spleen erythrocyte release, and selective redistribution of blood flow to the organs most vulnerable to lack of oxygen, such as the brain, heart, and lungs. However, this is a poorly studied form of hypoxia, with a knowledge gap on physiological and biochemical adaptation mechanisms.
TRIM67 Deficiency Exacerbates Hypothalamic Inflammation and Fat Accumulation in Obese Mice
Authors: Jia Lanlan , Chen Zhengli , Pan Ting , Xia Yu , He Junbo , Jahangir Asad , Wei Xiaoli , Liu Wentao , Shi Riyi , Huang Chao , Luo Qihui
Published: August 2022

Obesity has achieved the appearance of a global epidemic and is a serious cause for concern. The hypothalamus, as the central regulator of energy homeostasis, plays a critical role in regulating food intake and energy expenditure. In this study, we show that TRIM67 in the hypothalamus was responsive to body-energy homeostasis whilst a deficiency of TRIM67 exacerbated metabolic disorders in high-fat-diet-induced obese mice. We found exacerbated neuroinflammation and apoptosis in the hypothalamus of obese TRIM67 KO mice. We also found reduced BDNF in the hypothalamus, which affected the fat sympathetic nervous system innervation and contributed to lipid accumulation in adipose tissue under high-fat-diet exposure. In this study, we reveal potential implications between TRIM67 and the hypothalamic function responding to energy overuptake as well as a consideration for the therapeutic diagnosis of obesity.