bluuebunny/crossref_metadata_2025 huggingface dataset:
HIV and Substance Use in Latin America: A Scoping Review
Authors: Huff Hanalise V. , Carcamo Paloma M. , Diaz Monica M. , Conklin Jamie L. , Salvatierra Justina , Aponte Rocio , Garcia Patricia J.
Published: June 2022

This scoping review aims to explore the interplay between substance use (SU) and HIV in Latin America (LA). Database searches yielded 3481 references; 196 were included. HIV prevalence among people who used substances (PWUS) ranged from 2.8–15.2%. SU definitions were variable throughout studies, and thus data were not easily comparable. In 2019, only 2% of new HIV infections were attributed to injection drug use (IDU) in LA. Factors associated with HIV among PWUS included being female, IDU and homelessness, and PWUS were likely to engage in risky sexual behaviors, start antiretroviral treatment late, have poor adherence, have treatment failure, be lost to follow-up, have comorbidities, and experience higher mortality rates and lower quality of life, as has been reported in PLWH with SU in other regions. Five intervention studies were identified, and only one was effective at reducing HIV incidence in PWUS. Interventions in other regions have varying success depending on context-specific characteristics, highlighting the need to conduct more research in the LA region. Though progress has been made in establishing SU as a major concern in people living with HIV (PLWH), much more is yet to be done to reduce the burden of HIV and SU in LA.
Identifying Drug-Therapy Problems among Syrian Refugees in Zaatari Refugee Camp
Authors: Hammad Alaa M. , Al-Qerem Walid , Alasmari Fawaz , Ling Jonathan , Qarqaz Raghda , Alaqabani Hakam
Published: June 2022

Background: Due to a lack of proper pharmaceutical care, Syrian refugees in the Zaatari refugee camp are more likely to have drug-related issues, such as prescription errors and adverse drug occurrences. Aim: The current study aims to identify drug-therapy problems among Syrian refugees in the Zaatari refugee camp. Method: This is a retrospective cross-sectional study. Patients’ files were collected from the Zaatari camp database. Patients who were 18 years or older and were previously diagnosed with a chronic disease were included. A classification of drug therapy problems (DTPs) was adapted. Results: The data of 1530 adult patients (896 females) were collected. The mean age of the sample was 53.7 years and the mean Body mass Index (BMI) was 27.20. The mean of all taken medications was 4.01 (±2.33) medications, with a maximum number of 13. A total of 3572 DTPs was identified, with a mean of 2.33 (±1.26) DTPs per patient. Based on the above-mentioned classification, 70.32% of the DTPs were related to indication, 26.65% were related to effectiveness, and 3.03% were related to safety. Conclusion: This study found that refugees in the Zaatari refugee camp have numerous DTPs among their medications. Greater focus should be placed on their medical care, in order to prevent any future complications due to DTPs.
Jordan’s Pandemic Influenza Preparedness (PIP): A Reflection on COVID-19 Response
Authors: Kheirallah Khalid A. , Al-Nusair Mohammed , Aljabeiti Shahed , Sheikali Nadir , Alzoubi Abdallah , Alsulaiman Jomana W. , Al-Mistarehi Abdel-Hameed , Alzoubi Hamed , Bani Mousa Ayman Ahmad , Allouh Mohammed Z.
Published: June 2022

The COVID-19 pandemic made it clear to the world that better preparedness for future pandemics is paramount. This study aims to explore how the 2018 Jordan’s Pandemic Influenza Preparedness (PIP) assessment plan (conducted utilizing a standardized tool of the CDC National Inventory of Core Capabilities for Pandemic Influenza Preparedness and Response) reflected on the initial COVID-19 response. A qualitative, single intrinsic case study design, utilizing interpretivist approach, was utilized to interview subject-matter experts and explore the potential reflection of PIP assessment on COVID-19 response. Utilizing a mini-Delphi approach, the interviews aimed at generating an in-depth understanding of how the Jordan’s PIP risk assessment reflects on the country’s response to COVID-19. The following 12 core capabilities, along with their reflections on COVID-19, were assessed: country planning, research and use of findings, communications, epidemiologic capability, laboratory capability, routine influenza surveillance, national respiratory disease surveillance, outbreak response, resources for containment, community-based interventions to prevent the spread of influenza, infection control (IC), and health sector pandemic response. Jordan’s experience and preparedness for influenza may have served as a crucial guide to establishing success in COVID-19 control and mitigation. Surveillance, outbreak, and research activities were very well established in Jordan’s PIP, whereas surge capacity in human capital and health facility were identified as two high-risk areas. However, the limitation in these two areas was met during the COVID-19 response. Still, human capital suffered fatigue, and there was an evident lack of laboratory testing plans when COVID-19 cases increased. Jordan’s experience with PIP may have served as a guide for establishing successful COVID-19 control and mitigation. The established PIP principles, systems, and capacities seem to have reflected well on fighting against COVID-19 in terms of more efficient utilization of available surveillance, laboratory, outbreak management, and risk communications. This reflection facilitated a better mitigation and control of COVID-19.
Multivariate Statistical Analysis for the Detection of Air Pollution Episodes in Chemical Industry Parks
Authors: Zhao Xiangyu , Cheng Kuang , Zhou Wang , Cao Yi , Yang Shuang-Hua
Published: June 2022

Air pollution episodes (APEs) caused by excessive emissions from chemical industry parks (CIPs) have resulted in severe environmental damage in recent years. Therefore, it is of great importance to detect APEs timely and effectively using contaminant measurements from the air quality monitoring network (AQMN) in the CIP. Traditionally, APE can be detected by determining whether the contaminant concentration at any ambient monitoring station exceeds the national environmental standard. However, the environmental standards used are unified in various ambient monitoring stations, which ignores the source–receptor relationship in the CIP and challenges the effective detection of excessive emissions in some scenarios. In this paper, an approach based on a multivariate statistical analysis (MSA) method is proposed to detect the APEs caused by excessive emissions from CIPs. Using principal component analysis (PCA), the spatial relationships hidden among the historical environmental monitoring data are extracted, and the high-dimensional data are projected into only two subspaces. Then, two monitoring indices, T2 and Q, which represent the variability in these subspaces, are utilized to monitor the pollution status and detect the potential APEs in the CIP. In addition, the concept of APE detectability is also defined, and the condition for APE detectability is derived, which explains when the APEs can be detectable. A simulated case for a CIP in Zhejiang province of China is studied to evaluate the performance of this approach. The study indicates that the method can have an almost 100% APE detection rate. The real-world measurements of Total Volatile Organic Compounds (TVOC) at a 10-min time interval from 3 December 2020∼12 December 2020 are also analyzed, and 64 APEs caused by excessive TVOC emissions are detected in a total of 1440 time points.
Effects of Physicochemical Parameters on Struvite Crystallization Based on Kinetics
Authors: Wu Jinzhu , Li Yifan , Xu Baojian , Li Mei , Wang Jing , Shao Yuanyuan , Chen Feiyong , Sun Meng , Liu Bing
Published: June 2022

The precipitation of struvite (MgNH4PO4·6H2O) is considered to be a promising method for the recovery of phosphate from wastewater. In this review, the kinetic models, which are commonly used to explain the process of struvite crystallization, are described. The mixed-suspension mixed-product removal (MSMPR) model is based on the population balance equation (the size-dependent growth model and the size-independent growth model). Thereafter, the first-order kinetic fitting model that aligned with concentration changes in the substrate is summarized. Finally, the several physical and chemical factors that affected the efficiency of struvite crystallization are determined. The supersaturation ratio, which is seen as the driving force of struvite crystallization, is the main factor that influences crystallization; however, it cannot be used in practical applications of engineering because it is indirectly associated with the following factors: pH, the molar ratio of Mg:N:P, and the interference of foreign impurities. In this study, we present conclusions that should be used to guide further research studies, and encourage the engineering practice of wastewater treatment with struvite precipitation.
Longitudinal Predictors of Coronavirus-Related PTSD among Young Adults from Poland, Germany, Slovenia, and Israel
Authors: Ochnik Dominika , Rogowska Aleksandra M. , Arzenšek Ana , Benatov Joy
Published: June 2022

The aim of this study was to reveal longitudinal predictors of coronavirus-related PTSD and the moderating roles of country, sex, age, and student status among young adults from Poland, Germany, Slovenia, and Israel. We included the following predictors: perceived stress, exposure to COVID-19, perceived impact of COVID-19 on well-being in socioeconomic status (PNIC-SES) and social relationships (PNIC-SR), fear of COVID-19, fear of vaccination, and trust in institutions. We conducted the study online among a representative sample of 1723 young adults aged 20–40 (M = 30.74, SD = 5.74) years in February 2021 (T1) and May–June 2021 (T2). We used McNemar’s χ2 and the paired samples Student’s t-test to test differences over time. We assessed the relationships between variables using Pearson’s correlation. We performed structural equation modeling (SEM) to examine the associations between variables at T1 and T2. We used a lagged regression model to examine the causal influences between variables across different time points (T1 and T2). The results showed that all variables decreased over time, except exposure to COVID-19. The rates of infected, tested, and under-quarantine participants increased. The rates of those who lost a job and experienced worsening economic status decreased. The rate of hospitalized participants and those experiencing the loss of close ones did not change. Higher perceived stress, fear of COVID-19, fear of vaccination, and trust in institutions were significant longitudinal predictors of coronavirus-related PTSD regardless of country, sex, age, and student status. Institutions should provide more accurate programs for public health, so trust in institutions can be a protective and not a risk factor in future traumatic events.
Analysis of the Effect of Human-Machine Co-Driving Vehicle on Pedestrian Crossing Speed at Uncontrolled Mid-Block Road Sections: A VR-Based Case Study
Authors: Wang Kun , Xu Liang , Jiang Han
Published: June 2022

The current study investigates the effects of speed and time headway of human-machine co-driving vehicles on pedestrian crossing speed at uncontrolled mid-block road sections. A VR-based simulation study is conducted to study pedestrian crossing behaviour when facing human-machine co-driving vehicles. A total of 30 college students are recruited, and each participant is required to complete 5 street-crossing simulator trials facing human-machine co-driving vehicles with varying time headway levels and speeds. The correlations and differences between demographic information, time headway, vehicle speed, and pedestrian crossing speed are analyzed. The results show that gender and pedestrian’s trust in human-machine co-driving vehicles are significantly correlated with pedestrian crossing speed. The pedestrian crossing speed increases with the increase in vehicle speed and decreases with the increase in vehicle time headway. In addition, the time headway has a stronger correlation with the pedestrian crossing speed than the vehicle speed. The findings will provide theoretical and methodological support for the formulation of pedestrian crossing control measures in the stage of human-machine co-driving.
Occurrence, Distribution, and Risk Assessment of Antibiotics in the Aquatic Environment of the Karst Plateau Wetland of Yangtze River Basin, Southwestern China
Authors: Guo Feng , Wang Yanan , Peng Jie , Huang Hetian , Tu Xiangting , Zhao Hu , Zhan Nan , Rao Zhu , Zhao Gaofeng , Yang Hongbo
Published: June 2022

In this study, the occurrence, distribution, and ecological risk of 40 commonly used antibiotics, including 15 sulfonamides (SAs), 9 fluoroquinolones (FQs), 7 macrolides (MCs), 3 tetracyclines (TCs), 2 chloramphenicols (CAPs), and 4 other categories, in the aquatic environment of the karst plateau wetland Caohai of the Yangtze River basin in southwestern China are reported. In total, 27 antibiotics were detected, with the detection rate ranging from 5% to 100%. The total concentration at each site ranged from 21.8 ng/L to 954 ng/L, with the average concentration being 189 ng/L. FQs and MCs were the most predominant categories, contributing 29.3% and 25.0% of the total antibiotic burden. The five most commonly detected antibiotics were ciprofloxacin (CIP), oxytetracycline (OTC), acetyl sulfamethoxazole (ASMZ), norfloxacin (NOR), and florfenicol (FF). The spatial distribution of the total concentration at each site demonstrated a decreasing trend from the southeastern area upstream adjoining the main counties to the northwestern area downstream, indicating that human activities have a great impact. Meanwhile, the natural attenuation rates of different types of antibiotics in the direction of flow ranged from 17.6% to 100%, which implied the natural purification potential of the wetland for antibiotics. The cluster analysis results indicated that domestic sewage and wastewater from agriculture and animal husbandry were the main sources of contamination in the surrounding wetland. Risk quotients (RQs) assessment showed that most of the individuals were at low to medium risk and that the adverse risks posed by mixtures of antibiotics were higher than those posed by the individual antibiotics.
Research on the Effects of Soundscapes on Human Psychological Health in an Old Community of a Cold Region
Authors: Cui Peng , Li Tingting , Xia Zhengwei , Dai Chunyu
Published: June 2022

The acoustic environment of residential areas is critical to the health of the residents. To reveal the impact of the acoustic environment on people’s mental health and create a satisfactory acoustic setting, this study took a typical old residential area in Harbin as an example, conducted a field measurement and questionnaire survey on it, and took typical acoustic sources as the research object for human body index measurement. The relationship between heart rate (HR), skin conductivity level (SCL), physiological indicators, semantic differences (SD), and psychological indicators was studied. The sound distribution in the old community was obtained, determining that gender, age, and education level are significant factors producing different sound source evaluations. Music can alleviate residents’ psychological depression, while traffic sounds and residents’ psychological state can affect the satisfaction evaluation of the sound environment. There is a significant correlation between the physiological and psychological changes produced by different sounds. Pleasant sounds increase a person’s HR and decrease skin conductivity. The subjects’ HR increased 3.24 times per minute on average, and SCL decreased 1.65 times per minute on average in relation to hearing various sound sources. The SD evaluation showed that lively, pleasant, and attractive birdsongs and music produced the greatest HR and SCL changes, and that the sound barrier works best when placed 8 m and 18 m from the road.
Prevalence of Human Papillomavirus (HPV) in the Oral Cavity of a Healthy Population in South-Eastern Poland
Authors: Koleśnik Marcin , Stępień Ewa , Polz-Dacewicz Małgorzata
Published: June 2022

Human papillomavirus (HPV) is associated with both benign lesions and with neoplastic diseases, such as oropharyngeal cancer. Due to the increasing occurrence of these neoplasms on a global scale, it seems important to estimate the risk factors in the population. So far, data on the presence of oral HPV in the European population are scarce. Oral HPV was detected in 53 out of 461 healthy subjects (11.5%) in south-eastern Poland. Among the most common oncogenic types, HPV 16 was reported in four subjects (0.87%) and HPV 18 in three subjects (0.65%). Another high-risk type, HPV 45, was detected in nine subjects (1.95%). Low risk types (HPV 6, 11, 54) were detected in 25 cases, which constituted 5.4% of all tested samples. In adults and children, statistically more HPV positive cases have been reported in males than in females. A positive relationship was demonstrated between age and the amount of positive oral HPV. The presence of HPV was statistically more frequent in the population living in urban rather than in rural areas in all studied age groups (p < 0.05).
Efficient Removal of Nonylphenol Isomers from Water by Use of Organo-Hydrotalcites
Authors: Cosano Daniel , Esquivel Dolores , Romero-Salguero Francisco J. , Jiménez-Sanchidrián César , Ruiz José Rafael
Published: June 2022

The presence of potent organic endocrine-disrupting chemicals (EDCs) in natural aquifers can have adverse impacts on public health and the environment. 4-nonylphenol, one such EDC, can be efficiently removed from water by adsorption onto a clayey material. In this work, we created an effective sorbent for this purpose by using co-precipitation and subsequent ion-exchange to intercalate the organic anion deoxycholate into a Mg/Al hydrotalcite. Intercalating deoxycholate ions increased the organophilicity of the hydrotalcite surface. The solid was used to adsorb 4-nonylphenol at different pollutant concentrations and temperatures. The adsorption process was subjected to a kinetic study. Based on the results, the EDC was adsorbed by chemisorption. In addition, based on the equilibrium isotherms used for the process, the Freundlich model was the most accurate in reproducing the adsorption of 4-nonylphenol onto deoxycholate-intercalated hydrotalcite.
Association of Personality with Cognitive Failure among Japanese Middle-Aged and Older Adults
Authors: Iwasa Hajime , Yoshida Yuko , Ishioka Yoshiko , Suzukamo Yoshimi
Published: June 2022

This study explored the associations between personality traits and cognitive failure (including minor lapses and prospective and retrospective memory failure) among middle-aged and older adults living in Japan. The participants were 373 adults, aged 40–84 (167 men and 206 women). The 15-item Japanese version of the Short Inventory of Minor Lapses was used to evaluate minor lapses, and the 16-item Japanese version of the Prospective and Retrospective Memory Questionnaire was used to assess prospective and retrospective memory failure. The participants’ variables evaluated for their association with cognitive failure were gender, age, education, paid work, social network, chronic disease, sleep quality, and the Big Five personality traits (i.e., neuroticism, extraversion, openness, agreeableness, and conscientiousness). Multivariable regression analyses demonstrated that sleep quality (β = −0.232), neuroticism (β = 0.163), and conscientiousness (β = −0.295) were related to minor lapses; age (β = 0.152), sleep quality (β = −0.168), and conscientiousness (β = −0.290) were associated with prospective memory failure; and age (β = 0.268), sleep quality (β = −0.146), and conscientiousness (β = −0.221) were associated with retrospective memory failure. These findings may facilitate the development of efficient strategies for the prevention of cognitive dysfunction and its adverse consequences for personal health.
Impact of Climate Change Beliefs on Youths’ Engagement in Energy-Conservation Behavior: The Mediating Mechanism of Environmental Concerns
Authors: Han Ping , Tong Zepeng , Sun Yan , Chen Xuefeng
Published: June 2022

Global climate change presents a profound threat to the survival and continued development of humanity. The present study featured a survey of 3005 adolescents in China on 13 December 2021, aiming to determine whether climate change beliefs (including recognition of the existence of climate change, cognition of the causes of climate change, and climate change risk perception) influence their engagement in energy-conservation behaviors. Concurrently, the psychological mechanism underlying the influence of environmental concerns on the above relationship was also tested. The results showed that, among youths, climate change belief positively predicts engagement in energy-conservation behaviors. Specifically, awareness of the existence of climate change, knowledge of the causes of climate change, and climate change risk perception all positively predict engagement in energy-conservation behaviors. Further, environmental concerns were found to play a mediating role in the relationship between climate change beliefs and energy-conservation actions. From a practical perspective, the government and education departments should guide young people to develop accurate perceptions of climate change, and should raise their awareness of energy conservation and social responsibility, which should lead to their development of energy-conservation habits.
Structural and Functional Analysis of SHP Promoter and Its Transcriptional Response to FXR in Zn-Induced Changes to Lipid Metabolism
Authors: Gao Han , Fan Xing , Wu Qi-Chun , Chen Chuan , Xiao Fei , Wu Kun
Published: June 2022

Zinc alleviates hepatic lipid deposition, but the transcriptional regulatory mechanisms are still unclear. In this study, we characterized the promoter of an SHP (short heterodimer partner) in a teleost Pelteobagrus fulvidraco. The binding sites of an FXR (farnesoid X receptor) were predicted by the SHP promoter, indicating that the FXR mediated its transcriptional activity. The site mutagenesis and the EMSA (electrophoretic mobility shift assay) found that the −375/−384 bp FXR site on the SHP promoter was the functional binding locus responsible for the Zn-induced transcriptional activation. A further study of yellow catfish hepatocytes suggested that the activation of the FXR/SHP is responsible for the effect of Zn on the decreasing lipid content. Thus, this study provides direct evidence of the interaction between the FXR and SHP promoter in fish, and accordingly elucidates the potential transcriptional mechanism by which Zn reduces hepatic lipid accumulation.
Microbiome Changes in Connective Tissue Diseases and Vasculitis: Focus on Metabolism and Inflammation
Authors: La Barbera Lidia , Macaluso Federica , Fasano Serena , Grasso Giulia , Ciccia Francesco , Guggino Giuliana
Published: June 2022

The microbial community acts as an active player in maintaining homeostasis and immune functions through a continuous and changeable cross-talk with the host immune system. Emerging evidence suggests that altered microbial composition, known as dysbiosis, might perturb the delicate balance between the microbiota and the immune system, triggering inflammation and potentially contributing to the pathogenesis and development of chronic inflammatory diseases. This review will summarize the current evidence about the microbiome-immunity cross-talk, especially focusing on the microbiota alterations described in patients with rheumatic diseases and on the recent findings concerning the interaction between microbiota, metabolic function, and the immune system.
Regulation of Phenolic Compound Production by Light Varying in Spectral Quality and Total Irradiance
Authors: Pech Radomír , Volná Adriana , Hunt Lena , Bartas Martin , Červeň Jiří , Pečinka Petr , Špunda Vladimír , Nezval Jakub
Published: June 2022

Photosynthetically active radiation (PAR) is an important environmental cue inducing the production of many secondary metabolites involved in plant oxidative stress avoidance and tolerance. To examine the complex role of PAR irradiance and specific spectral components on the accumulation of phenolic compounds (PheCs), we acclimated spring barley (Hordeum vulgare) to different spectral qualities (white, blue, green, red) at three irradiances (100, 200, 400 µmol m−2 s−1). We confirmed that blue light irradiance is essential for the accumulation of PheCs in secondary barley leaves (in UV-lacking conditions), which underpins the importance of photoreceptor signals (especially cryptochrome). Increasing blue light irradiance most effectively induced the accumulation of B-dihydroxylated flavonoids, probably due to the significantly enhanced expression of the F3′H gene. These changes in PheC metabolism led to a steeper increase in antioxidant activity than epidermal UV-A shielding in leaf extracts containing PheCs. In addition, we examined the possible role of miRNAs in the complex regulation of gene expression related to PheC biosynthesis.
Development of High-Efficiency, Magnetically Separable Palladium-Decorated Manganese-Ferrite Catalyst for Nitrobenzene Hydrogenation
Authors: Hajdu Viktória , Muránszky Gábor , Nagy Miklós , Kopcsik Erika , Kristály Ferenc , Fiser Béla , Viskolcz Béla , Vanyorek László
Published: June 2022

Aniline (AN) is one of the most important compounds in the chemical industry and is prepared by the catalytic hydrogenation of nitrobenzene (NB). The development of novel, multifunctional catalysts which are easily recoverable from the reaction mixture is, therefore, of paramount importance. Compared to conventional filtration, magnetic separation is favored because it is cheaper and more facile. For satisfying these requirements, we developed manganese ferrite (MnFe2O4)–supported, magnetically separable palladium catalysts with high catalytic activity in the hydrogenation of nitrobenzene to aniline. In addition to high NB conversion and AN yield, remarkable aniline selectivity (above 96 n/n%) was achieved. Surprisingly, the magnetic support alone also shows moderate catalytic activity even without noble metals, and thus, up to 94 n/n% nitrobenzene conversion, along with 47 n/n% aniline yield, are attainable. After adding palladium nanoparticles to the support, the combined catalytic activity of the two nanomaterials yielded a fast, efficient, and highly selective catalyst. During the test of the Pd/MnFe2O4 catalyst in NB hydrogenation, no by-products were detected, and consequently, above 96 n/n% aniline yield and 96 n/n% selectivity were achieved. The activity of the Pd/MnFe2O4 catalyst was not particularly sensitive to the hydrogenation temperature, and reuse tests indicate its applicability in at least four cycles without regeneration. The remarkable catalytic activity and other favorable properties can make our catalyst potentially applicable to both NB hydrogenation and other similar or slightly different reactions.
Cellular Environment and Phenotypic Heterogeneity: How Data-Driven Modeling Finds the Smoking Gun
Authors: Guilbert Marie , Courtade Emmanuel , Thommen Quentin
Published: June 2022

The cellular environment modifies cellular phenotypes, in particular, the stress response phenotype, which easily exhibits high phenotypic heterogeneity due to the common characteristics of its regulatory networks. The aim of this work is to quantify and interpret the impact of collagen type I, a major component of the cellular environment, on the phenotypic heterogeneity of the cellular response. Our approach combines in an original way the monitoring of the response of a single cell and the mathematical modeling of the network. After a detailed statistical description of the phenotypic heterogeneity of the cellular response, the mathematical modeling explains how the observed changes can be explained by an induced increase in the average expression of a central protein of the regulatory network. The predictions of the data-driven model are fully consistent with the biochemical measurements performed. The framework presented here is also a new general methodology to study phenotypic heterogeneity, although we focus here on the response to proteotoxic stress in HeLa cells.
Collaborative Action of Microglia and Astrocytes Mediates Neutrophil Recruitment to the CNS to Defend against Escherichia coli K1 Infection
Authors: Liu Peng , Wang Xinyue , Yang Qian , Yan Xiaolin , Fan Yu , Zhang Si , Wei Yi , Huang Min , Jiang Lingyan , Feng Lu
Published: June 2022

Escherichia coli K1 is a leading cause of neonatal bacterial meningitis. Recruitment of neutrophils to the central nervous system (CNS) via local immune response plays a critical role in defense against E. coli K1 infection; however, the mechanism underlying this recruitment remains unclear. In this study, we report that microglia and astrocytes are activated in response to stimulation by E. coli K1 and/or E. coli K1-derived outer membrane vesicles (OMVs) and work collaboratively to drive neutrophil recruitment to the CNS. Microglial activation results in the release of the pro-inflammatory cytokine TNF-α, which activates astrocytes, resulting in the production of CXCL1, a chemokine critical for recruiting neutrophils. Mice lacking either microglia or TNF-α exhibit impaired production of CXCL1, impaired neutrophil recruitment, and an increased CNS bacterial burden. C-X-C chemokine receptor 2 (CXCR2)-expressing neutrophils primarily respond to CXCL1 released by astrocytes. This study provides further insights into how immune responses drive neutrophil recruitment to the brain to combat E. coli K1 infection. In addition, we show that direct recognition of E. coli K1 by microglia is prevented by the K1 capsule. This study also reveals that OMVs are sufficient to induce microglial activation.
The Less We Eat, the Longer We Live: Can Caloric Restriction Help Us Become Centenarians?
Authors: Dakic Tamara , Jevdjovic Tanja , Vujovic Predrag , Mladenovic Aleksandra
Published: June 2022

Striving for longevity is neither a recent human desire nor a novel scientific field. The first article on this topic was published in 1838, when the average human life expectancy was approximately 40 years. Although nowadays people on average live almost as twice as long, we still (and perhaps more than ever) look for new ways to extend our lifespan. During this seemingly endless journey of discovering efficient methods to prolong life, humans were enthusiastic regarding several approaches, one of which is caloric restriction (CR). Where does CR, initially considered universally beneficial for extending both lifespan and health span, stand today? Does a lifelong decrease in food consumption represent one of the secrets of centenarians’ long and healthy life? Do we still believe that if we eat less, we will live longer? This review aims to summarize the current literature on CR as a potential life-prolonging intervention in humans and discusses metabolic pathways that underlie this effect.
Synthesis and Anti-Cancer Activity of New Pyrazolinyl-Indole Derivatives: Pharmacophoric Interactions and Docking Studies for Identifying New EGFR Inhibitors
Authors: Khalilullah Habibullah , Agarwal Deepak K. , Ahsan Mohamed J. , Jadav Surender S. , Mohammed Hamdoon A. , Khan Masood Alam , Mohammed Salman A. A. , Khan Riaz
Published: June 2022

Newly designed series of indole-containing pyrazole analogs, pyrazolinylindoles, were synthesized, and their structures were confirmed based on the spectral data of the 1H NMR, 13C NMR, and HR-MS analyses. Preliminary anti-cancer activity testings were carried out by the National Cancer Institute, United States of America (NCI, USA). Compounds HD02, HD05, and HD12 demonstrated remarkable cytotoxic activities against nine categories of cancer types based cell line panels which included leukemia, colon, breast, melanoma, lungs, renal, prostate, CNS, and ovarian cancer cell lines. The highest cytotoxic effects were exhibited by the compounds HD02 [1-(5-(1-H-indol-3-yl)-3-(p-tolyl)-4,5-dihydro-1H-pyrazol-1-yl)-2-phenylethanone], HD05 [1-(3-(4-chlorophenyl)-5-(1H-indol-3-yl)-4,5-dihydro-1H-pyrazol-1-yl)-2-phenoxyethanone], and HD12 [(3-(4-chlorophenyl)-5-(1H-indol-3-yl)-4,5-dihydro-1H-pyrazol-1-yl)(pyridin-4-yl)methanone] against some of the 56 types of NCI-based cell lines in different panels. Compound HD05 showed the maximum range of cancer cell growth inhibitions against all categories of the cell lines in all nine panels. On average, in comparison to the referral standard, imatinib, at a dose level of 10 µM, the HD05 showed significant activity against leukemia in the range of 78.76%, as compared to the imatinib at 9% of cancer cells’ growth inhibitions. Molecular docking simulation studies were performed in silico on the epidermal growth factor receptor (EGFR) tyrosine kinase, in order to validate the activity.
Role of miR-133/Dio3 Axis in the T3-Dependent Modulation of Cardiac mitoK-ATP Expression
Authors: Canale Paola , Nicolini Giuseppina , Pitto Letizia , Kusmic Claudia , Rizzo Milena , Balzan Silvana , Iervasi Giorgio , Forini Francesca
Published: June 2022

The opening of the ATP-sensitive mitochondrial potassium channel (mitok-ATP) is a common goal of cardioprotective strategies in the setting of acute and chronic myocardial disease. The biologically active thyroid hormone (TH), 3-5-3-triiodothyronine (T3), has been indicated as a potential activator of mitoK-ATP but the underlying mechanisms are still elusive. Here we describe a novel role of T3 in the transcriptional regulation of mitoK and mitoSur, the recently identified molecular constituents of the channel. To mimic human ischemic heart damage, we used a rat model of a low T3 state as the outcome of a myocardial ischemia/reperfusion event, and neonatal rat cardiomyocytes (NRCM) challenged with hypoxia or H2O2. Either in the in vivo or in vitro models, T3 administration to recover the physiological concentrations was able to restore the expression level of both the channel subunits, which were found to be downregulated under the stress conditions. Furthermore, the T3-mediated transcriptional activation of mitoK-ATP in the myocardium and NRCM was associated with the repression of the TH-inactivating enzyme, deiodinase 3 (Dio3), and an up-regulation of the T3-responsive miR-133a-3p. Mechanistically, the loss and gain of function experiments and reporter gene assays performed in NRCM, have revealed a new regulatory axis whereby the silencing of Dio3 under the control of miR-133a-3p drives the T3-dependent modulation of cardiac mitoK and mitoSur transcription.
Silicon Nitride as a Biomedical Material: An Overview
Authors: Du Xiaoyu , Lee Seunghun S. , Blugan Gurdial , Ferguson Stephen J.
Published: June 2022

Silicon nitride possesses a variety of excellent properties that can be specifically designed and manufactured for different medical applications. On the one hand, silicon nitride is known to have good mechanical properties, such as high strength and fracture toughness. On the other hand, the uniqueness of the osteogenic/antibacterial dualism of silicon nitride makes it a favorable bioceramic for implants. The surface of silicon nitride can simultaneously inhibit the proliferation of bacteria while supporting the physiological activities of eukaryotic cells and promoting the healing of bone tissue. There are hardly any biomaterials that possess all these properties concurrently. Although silicon nitride has been intensively studied as a biomedical material for years, there is a paucity of comprehensive data on its properties and medical applications. To provide a comprehensive understanding of this potential cornerstone material of the medical field, this review presents scientific and technical data on silicon nitride, including its mechanical properties, osteogenic behavior, and antibacterial capabilities. In addition, this paper highlights the current and potential medical use of silicon nitride and explains the bottlenecks that need to be addressed, as well as possible solutions.
Platelet-Rich Plasma as an Alternative to Xenogeneic Sera in Cell-Based Therapies: A Need for Standardization
Authors: Anitua Eduardo , Zalduendo Mar , Troya Maria , Alkhraisat Mohammad H. , Blanco-Antona Leticia Alejandra
Published: June 2022

There has been an explosion in scientific interest in using human-platelet-rich plasma (PRP) as a substitute of xenogeneic sera in cell-based therapies. However, there is a need to create standardization in this field. This systematic review is based on literature searches in PubMed and Web of Science databases until June 2021. Forty-one studies completed the selection criteria. The composition of PRP was completely reported in less than 30% of the studies. PRP has been used as PRP-derived supernatant or non-activated PRP. Two ranges could be identified for platelet concentration, the first between 0.14 × 106 and 0.80 × 106 platelets/µL and the second between 1.086 × 106 and 10 × 106 platelets/µL. Several studies have pooled PRP with a pool size varying from four to nine donors. The optimal dose for the PRP or PRP supernatant is 10%. PRP or PRP-derived supernatants a have positive effect on MSC colony number and size, cell proliferation, cell differentiation and genetic stability. The use of leukocyte-depleted PRP has been demonstrated to be a feasible alternative to xenogeneic sera. However, there is a need to improve the description of the PRP preparation methodology as well as its composition. Several items are identified and reported to create guidelines for future research.
Monocyte–Macrophage Lineage Cell Fusion
Authors: Kloc Malgorzata , Subuddhi Arijita , Uosef Ahmed , Kubiak Jacek Z. , Ghobrial Rafik M.
Published: June 2022

Cell fusion (fusogenesis) occurs in natural and pathological conditions in prokaryotes and eukaryotes. Cells of monocyte–macrophage lineage are highly fusogenic. They create syncytial multinucleated giant cells (MGCs) such as osteoclasts (OCs), MGCs associated with the areas of infection/inflammation, and foreign body-induced giant cells (FBGCs). The fusion of monocytes/macrophages with tumor cells may promote cancer metastasis. We describe types and examples of monocyte–macrophage lineage cell fusion and the role of actin-based structures in cell fusion.
Determination of Intra- and Extracellular Metabolic Adaptations of 3D Cell Cultures upon Challenges in Real-Time by NMR
Authors: Urzì Christian , Hertig Damian , Meyer Christoph , Maddah Sally , Nuoffer Jean-Marc , Vermathen Peter
Published: June 2022

NMR flow devices provide longitudinal real-time quantitative metabolome characterisation of living cells. However, discrimination of intra- and extracellular contributions to the spectra represents a major challenge in metabolomic NMR studies. The present NMR study demonstrates the possibility to quantitatively measure both metabolic intracellular fingerprints and extracellular footprints on human control fibroblasts by using a commercially available flow tube system with a standard 5 mm NMR probe. We performed a comprehensive 3D cell culture system characterisation. Diffusion NMR was employed for intra- and extracellular metabolites separation. In addition, complementary extracellular footprints were determined. The implemented perfused NMR bioreactor system allowed the determination of 35 metabolites and intra- and extracellular separation of 19 metabolites based on diffusion rate differences. We show the reliability and sensitivity of NMR diffusion measurements to detect metabolite concentration changes in both intra- and extracellular compartments during perfusion with different selective culture media, and upon complex I inhibition with rotenone. We also demonstrate the sensitivity of extracellular footprints to determine metabolic variations at different flow rates. The current method is of potential use for the metabolomic characterisation of defect fibroblasts and for improving physiological comprehension.
Role of the Ribonuclease ONCONASE in miRNA Biogenesis and tRNA Processing: Focus on Cancer and Viral Infections
Authors: Menegazzi Marta , Gotte Giovanni
Published: June 2022

The majority of transcribed RNAs do not codify for proteins, nevertheless they display crucial regulatory functions by affecting the cellular protein expression profile. MicroRNAs (miRNAs) and transfer RNA-derived small RNAs (tsRNAs) are effectors of interfering mechanisms, so that their biogenesis is a tightly regulated process. Onconase (ONC) is an amphibian ribonuclease known for cytotoxicity against tumors and antiviral activity. Additionally, ONC administration in patients resulted in clinical effectiveness and in a well-tolerated feature, at least for lung carcinoma and malignant mesothelioma. Moreover, the ONC therapeutic effects are actually potentiated by cotreatment with many conventional antitumor drugs. This review not only aims to describe the ONC activity occurring either in different tumors or in viral infections but also to analyze the molecular mechanisms underlying ONC pleiotropic and cellular-specific effects. In cancer, data suggest that ONC affects malignant phenotypes by generating tRNA fragments and miRNAs able to downregulate oncogenes expression and upregulate tumor-suppressor proteins. In cells infected by viruses, ONC hampers viral spread by digesting the primer tRNAs necessary for viral DNA replication. In this scenario, new therapeutic tools might be developed by exploiting the action of ONC-elicited RNA derivatives.
TRX2/Rab35 Interaction Impairs Exosome Secretion by Inducing Rab35 Degradation
Authors: Zhang Tao , Zhao Lili , Han Liping , Li Yan , Hu Lanlin , Wang Huani , Zou Fangdong
Published: June 2022

Given that exosomes mediate intercellular communication by delivering cellular components to recipient cells or tissue, they have the potential to be engineered to deliver therapeutic payloads. However, the regulatory mechanism of exosome secretion is poorly understood. In addition, mitochondrial components have been found in exosomes, suggesting communication between mitochondria and exosomes. However, the molecular mechanism of the mitochondria and vesicle interaction remains unclear. Here, we showed that mitochondrial thioredoxin 2 (TRX2) decreased exosome concentrations and inhibited HCT116 cell migration. Coimmunoprecipitation/mass spectrometry (Co-IP/MS) showed that TRX2 interacted with Rab35. TRX2 and Rab35 bound to each other at their N-terminal motifs and colocalized on mitochondria. Furthermore, TRX2 induced Rab35 degradation, resulting in impaired exosome secretion. Additionally, Rab35 mediated the suppressive effects of TRX2 on cell migration, and TRX2 suppressed cell migration through exosomes. Taken together, this study first found an interaction between TRX2 and Rab35. These results revealed a new role for TRX2 in the regulation of exosome secretion and cell migration and explained the upstream regulatory mechanism of Rab35. Furthermore, these findings also provide new molecular evidence for communication between mitochondria and vesicles.
Slaying (Yet Again) the Brain-Eating Zombie Called the “Isochore Theory”: A Segmentation Algorithm Used to “Confirm” the Existence of Isochores Creates “Isochores” Where None Exist
Authors: Graur Dan
Published: June 2022

The isochore theory, which was proposed more than 40 years ago, depicts the mammalian genome as a mosaic of long, homogeneous regions that are characterized by their guanine and cytosine (GC) content. The human genome, for instance, was claimed to consist of five compositionally distinct isochore families. The isochore theory, in all its reincarnations, has been repeatedly falsified in the literature, yet isochore proponents have persistently resurrected it by either redefining isochores or by proposing alternative means of testing the theory. Here, I deal with the latest attempt to salvage this seemingly immortal zombie—a sequence segmentation method called isoSegmenter, which was claimed to “identify” isochores while at the same time disregarding the main characteristic attribute of isochores—compositional homogeneity. I used a series of controlled, randomly generated simulated sequences as a benchmark to study the performance of isoSegmenter. The main advantage of using simulated sequences is that, unlike real data, the exact start and stop point of any isochore or homogeneous compositional domain is known. Based on three key performance metrics—sensitivity, precision, and Jaccard similarity index—isoSegmenter was found to be vastly inferior to isoPlotter, a segmentation algorithm with no user input. Moreover, isoSegmenter identified isochores where none exist and failed to identify compositionally homogeneous sequences that were shorter than 100−200 kb. Will this zillionth refutation of “isochores” ensure a final and permanent entombment of the isochore theory? This author is not holding his breath.
Long Non-Coding RNA MIR31HG Promotes the Transforming Growth Factor β-Induced Epithelial-Mesenchymal Transition in Pancreatic Ductal Adenocarcinoma Cells
Authors: Ko Ching-Chung , Hsieh Yao-Yu , Yang Pei-Ming
Published: June 2022

The epithelial-to-mesenchymal transition (EMT) describes a biological process in which polarized epithelial cells are converted into highly motile mesenchymal cells. It promotes cancer cell dissemination, allowing them to form distal metastases, and also involves drug resistance in metastatic cancers. Transforming growth factor β (TGFβ) is a multifunctional cytokine that plays essential roles in development and carcinogenesis. It is a major inducer of the EMT. The MIR31 host gene (MIR31HG) is a newly identified long non-coding (lnc)RNA that exhibits ambiguous roles in cancer. In this study, a cancer genomics analysis predicted that MIR31HG overexpression was positively correlated with poorer disease-free survival of pancreatic ductal adenocarcinoma (PDAC) patients, which was associated with upregulation of genes related to TGFβ signaling and the EMT. In vitro evidence demonstrated that TGFβ induced MIR31HG expression in PDAC cells, and knockdown of MIR31HG expression reversed TGFβ-induced EMT phenotypes and cancer cell migration. Therefore, MIR31HG has an oncogenic role in PDAC by promoting the EMT.
Novel Insight into the Potential Role of Acylglycerophosphate Acyltransferases Family Members on Triacylglycerols Synthesis in Buffalo
Authors: Ma Xiao-ya , Duan An-qin , Lu Xing-rong , Liang Sha-sha , Sun Pei-hao , Sohel Md Mahmodul Hasan , Abdel-Shafy Hamdy , Amin Ahmed , Liang Ai-xin , Deng Ting-xian
Published: June 2022

Acylglycerophosphate acyltransferases (AGPATs) are the rate-limiting enzymes for the de novo pathway of triacylglycerols (TAG) synthesis. Although AGPATs have been extensively explored by evolution, expression and functional studies, little is known on functional characterization of how many members of the AGPAT family are involved in TAG synthesis and their impact on the cell proliferation and apoptosis. Here, 13 AGPAT genes in buffalo were identified, of which 12 AGPAT gene pairs were orthologous between buffalo and cattle. Comparative transcriptomic analysis and real-time quantitative reverse transcription PCR (qRT-PCR) further showed that both AGPAT1 and AGPAT6 were highly expressed in milk samples of buffalo and cattle during lactation. Knockdown of AGPAT1 or AGPAT6 significantly decreased the TAG content of buffalo mammary epithelial cells (BuMECs) and bovine mammary epithelial cells (BoMECs) by regulating lipogenic gene expression (p < 0.05). Knockdown of AGPAT1 or AGPAT6 inhibited proliferation and apoptosis of BuMECs through the expression of marker genes associated with the proliferation and apoptosis (p < 0.05). Our data confirmed that both AGPAT1 and AGPAT6 could regulate TAG synthesis and growth of mammary epithelial cells in buffalo. These findings will have important implications for understanding the role of the AGPAT gene in buffalo milk performance.