bluuebunny/crossref_metadata_2025 huggingface dataset:
Benzo[A]Pyrene Biodegradation by Multiple and Individual Mesophilic Bacteria under Axenic Conditions and in Soil Samples
Authors: Nzila Alexis , Musa Musa M. , Afuecheta Emmanuel , Al-Thukair Assad , Sankaran Saravanan , Xiang Lei , Li Qing X.
Published: January 2023

To date, only a handful of bacterial strains that can independently degrade and utilize benzo[a]pyrene (BaP) as the sole carbon source has been isolated and characterized. Here, three new bacterial strains—JBZ1A, JBZ2B, and JBZ5E—were isolated from contaminated soil and, using 16S rRNA sequencing, were identified as Brad rhizobium japonicum, Micrococcus luteus, and Bacillus cereus, respectively. The growth ability of each individual strain and a consortium of all strains in the presence of BaP (4–400 µmol·L−1, pH 7, 37 °C) was identified by the doubling time (dt). The results illustrate that dt decreased with increasing BaP concentrations for individual strains and the consortium. The optimum growth conditions of the consortium were 37 °C, 0.5% NaCl (w/v), and pH 7. Under these conditions, the degradation rate was 1.06 µmol·L−1·day−1, whereas that of individual strains ranged from 0.9 to 0.38 µmol·L−1·day−1. B. cereus had the strongest contribution to the consortium’s activity, with a degradation rate of 0.9 µmol·L−1·day−1. The consortium could also remove BaP spiked with soil but at a lower rate (0.01 µmol L−1.day−1). High-performance liquid chromatography–high-resolution tandem mass spectrometry permitted the detection of the metabolites of these strains, and a biodegradation pathway is proposed.
The Influence of Previous Lifestyle on Occupational Physical Fitness in the Context of Military Service
Authors: Oja Leila , Piksööt Jaanika
Published: January 2023

The Estonian Defense Forces are the basis of military service, mandatory for all male citizens of the Republic of Estonia who are at least 17 years old. The physical load in military service, especially in the first stage, is significantly greater than for men in everyday life. Therefore, it is important to know if health promotion in civilian life adequately prepares young people for military service and to what extent pre-military health behaviors affect physical performance during service. The purpose of this work was to examine conscripts’ physical fitness at different stages of military service and its relationships with previous lifestyle. Soldiers’ physical fitness was estimated three times during military service using three tests: sit-ups, push-ups and 2-mile run. Lifestyle and socio-economic background data was collected by a web-based questionnaire (n = 235). Linear regression analysis was performed using Army Physical Fitness Test (APFT) scores as dependent variables and questionnaire data as independent variables. The socio-economic background variables had no effect on physical fitness scores throughout the training period (p > 0.05). Young men that were physically more active daily, did sports, had healthier diet and did not smoke before entering military service showed better physical fitness test results throughout the period of service (p < 0.05). The effect of participation in sports was evident, as the conscripts with previous sports experiences demonstrated higher fitness tests scores (p < 0.01). These findings show that health promotion initiatives or programs for promoting physical activity and healthy diet, and preventing obesity and tobacco use, can also have a positive effect on the physical performance of young men during military service.
Effect of Azithromycin on Exacerbations in Asthma Patients with Obesity: Protocol for a Multi-Center, Prospective, Single-Arm Intervention Study
Authors: Tashiro Hiroki , Takahashi Koichiro , Uchida Masaru , Kurihara Yuki , Sadamatsu Hironori , Takamori Ayako , Kimura Shinya , Sueoka-Aragane Naoko
Published: January 2023

Introduction: Obesity is associated with severe asthma, but no specific treatment has been established. The gut microbiome is increasingly recognized as a crucial factor, but specific treatments focused on the gut microbiome have not been established. Recently, azithromycin has been found to have the capacity to attenuate exacerbations, a characteristic of severe asthma. The effect of azithromycin on obesity-induced severe asthma is not understood. Methods: The purpose of the present study is to clarify the effect of azithromycin on exacerbations in asthmatic patients with obesity. To explore the mechanism, the gut microbiome, metabolites of microbes such as short-chain fatty acids, and blood inflammatory cytokines will be analyzed to evaluate the correlation with the effect of azithromycin on exacerbations in obesity-induced severe asthma. A multi-center, prospective, single-arm intervention study is planned. Discussion: The present study will allow us to evaluate the effect of azithromycin on exacerbations, particularly in asthma patients with obesity, and explore biomarkers, targeting molecules including the gut microbiome, which are correlated with decreased exacerbations. The present results could contribute to identifying new therapeutic prospects and targeted microbes or molecules associated with severe clinical characteristics in asthmatic patients with obesity. Trial registration: This study has been registered as a prospective study with the University Hospital Medical Information Network (UMIN0000484389) and the Japan Registry of Clinical Trials (jRCTs071220023).
Physical Activity and Sleep Quality Association in Different Populations: A Meta-Analysis
Authors: Zhao Haitao , Lu Chuntian , Yi Cuixia
Published: January 2023

The meta-analysis statistical methodology was used to test the effect of physical activity intervention on sleep quality. According to the preliminary results of the meta-analysis, moderating variables (age stage and physical activity intensity) were included for further study. On this basis, measures and schemes to improve sleep quality through physical activity were put forward. A preliminary Endnote X9 search of relevant literature from six electronic databases (Web of Science, Medline, PubMed, CNKI, PsycINFO and Wanfang) was performed. The results showed the following: (1) The overall test effect of physical activity intervention on sleep quality was not significant (p = 0.15). (2) Moderate- and low-intensity physical activity had significant effects on sleep quality (moderate intensity d = 2.56, p = 0.015; low-intensity d = 1.38, p = 0.03), while high-intensity physical activity had no obvious effect on sleep quality (d = 1.12, p = 0.32). (3) There were differences in the effect of physical activity on sleep quality at different ages. The effect of physical activity on sleep quality was more obvious in children and middle-aged and elderly people (children d = 1.24, p = 0.03; middle-aged and elderly people d = 1.98, p = 0.037), but not in young people (d = 1.32, p = 0.11). Conclusion: The overall effect of physical activity on sleep quality was not significant. Physical activity had an obvious effect on the sleep quality of children and middle-aged and elderly people but had no obvious effect on young people. Moderate-intensity physical activity had a certain effect on sleep quality, but high-intensity physical activity had no obvious effect on sleep quality. Future studies need to confirm these findings with a good large sample and moderating variables.
Molecular Cloning and Characterization of a Serotonin N-Acetyltransferase Gene, xoSNAT3, from Xanthomonas oryzae pv. oryzae
Authors: Chen Xian , Zhao Yancun , Laborda Pedro , Yang Yong , Liu Fengquan
Published: January 2023

Rice bacterial blight (BB), caused by Xanthomonas oryzae pv. oryzae (Xoo), is one of the top ten bacterial plant diseases worldwide. Serotonin N-acetyltransferase (SNAT) is one of the key rate-limiting enzymes in melatonin (MT) biosynthesis. However, its function in pathogenic bacteria remains unclear. In this study, a Xoo SNAT protein (xoSNAT3) that showed 27.39% homology with sheep SNAT was identified from a collection of 24 members of GCN5-related N-acetyltransferase (GNAT) superfamily in Xoo. This xoSNAT3 could be induced by MT. In tobacco-based transient expression system, xoSNAT3 was found localized on mitochondria. In vitro studies indicated that xoSNAT3 showed the optima enzymatic activity at 50 °C. The recombinant enzyme showed Km and Vmax values of 709.98 μM and 2.21 nmol/min/mg protein, respectively. Mutant △xoSNAT3 showed greater impaired MT biosynthesis than the wild-type strain. Additionally, △xoSNAT3 showed 14.06% less virulence and 26.07% less biofilm formation. Collectively, our results indicated that xoSNAT3 services as a SNAT involved in MT biosynthesis and pathogenicity in Xoo.
Removal of Hexavalent Chromium in Aqueous Solution by Cellulose Filter Paper Loaded with Nano-Zero-Valent Iron: Performance Investigation and Numerical Modeling
Authors: Li Huali , Ren Zhongyu , Huang Dan , Jing Qi , Tang Haokai
Published: January 2023

Cr(VI) pollution in water bodies is very harmful to human health and the environment. Therefore, it is necessary to remove Cr(VI) from water. In this study, the composite (FP-nZVI) was prepared by loading nano-zero-valent iron (nZVI) onto cellulose filter paper (FP) using a liquid-phase reduction method to improve the dispersibility and oxidation resistance of nZVI. In batch experiments, the effects of iron loading of FP-nZVI, initial concentration of Cr(VI), temperature, and pH on Cr(VI) removal were particularly investigated. The maximum removal rate of 98.6% was achieved at 25 °C, pH = 5, initial concentration of Cr(VI) of 20 mg/L, and FeCl3·6H2O solution concentration of 0.8 mol/L. The removal of Cr(VI) by FP-nZVI conformed to a pseudo-second-order kinetic model and Langmuir isotherm model. The mechanism of Cr(VI) removal was a multi-step removal mechanism, involving adsorption, reduction, and coprecipitation. Column experiments investigated the effect of flow rate (1 mL/min, 3 mL/min, and 5 mL/min) on Cr(VI) removal. We found that increasing flow rate slightly decreased the removal rate of Cr(VI). The transport of Cr(VI) in composite porous media was simulated using HYDRUS-1D, and the results show that the two-site model can well simulate the reactive transport of Cr(VI). This study may provide a useful reference for the remediation of groundwater contaminated with Cr(VI) or other similar heavy metals using FP-nZVI.
Attitudes towards Trans Men and Women in Spain: An Adaptation of the ATTMW Scale
Authors: López-Sáez Miguel Ángel , Angulo-Brunet Ariadna , Platero Lucas R. , Bochicchio Vincenzo , Lecuona Oscar
Published: January 2023

This article presents the results of the adaptation and validation of the Attitudes Toward Trans Men and Women (ATTMW) scale—a measure capable of detecting transphobic positions towards trans men and women—in the Spanish context. A total of 310 prospective teachers from different stages of education participated in the study on its adaptation. In order to provide quantitative evidence of validity, confirmatory factor analysis and regression analysis with different constructs and sociodemographic variables were carried out. Internal consistency reliability was adequate. The study demonstrated that the ATTMW is a psychometrically sound instrument for the assessment of attitudes towards trans people, especially with items that categorize trans women and men as second-class people.
Preventing Punitive Violence: Implementing Positive Discipline in Everyday Parenting (PDEP) with Marginalized Populations in Bangladesh
Authors: Ateah Christine A. , Khondkar Laila , Milon Firozul , Rabbani Rasheda
Published: January 2023

Physical and other types of punishment remain common in Bangladesh, despite overwhelming evidence of their harm and worldwide efforts to decrease their use. One of the strategic priorities of Save the Children in Bangladesh’s Child Protection Program is to protect children from physical and humiliating punishment in homes, schools, and other settings. Save the Children in Bangladesh selected the Positive Discipline in Everyday Parenting (PDEP) Program to provide parents with alternatives to physical punishment that comply with human rights standards while strengthening relationships and understanding of child development. High-risk communities where children are particularly vulnerable were selected for this project. The PDEP program was delivered to 857 parents living in lower socioeconomic areas of Bangladesh, including ethnic minority groups, and parents living in urban slums of Dhaka and rural brothel areas. Due to the low levels of education of the participants (almost two-thirds of participants had not completed elementary school), simplified pre and posttests were utilized. Following program completion, parents’ approval of both physical punishment and punishment in general declined; they were less likely to view typical parent-child conflicts as intentional misbehavior and were less reactive to frustration. In addition, parents indicated an increased understanding of the positive discipline and more confidence in their parenting skills. Before taking PDEP, 64% of the parents often felt like they just did not know what to do as a parent, compared to 34% following program completion. PDEP demonstrated the potential to decrease the use of physical and humiliating punishments by parents living in high-risk communities in Bangladesh.
Satisfaction with Life and Nutritional Behaviour, Body Composition, and Functional Fitness of Women from the Kraków Population Participating in the “Healthy Active Senior” Programme
Authors: Gacek Maria , Wojtowicz Agnieszka , Kosiba Grażyna , Majer Magdalena , Gradek Joanna , Koteja Agnieszka , Czerwińska-Ledwig Olga
Published: January 2023

Pro-health behaviours are related to a person’s personal resources. The aim of the study was to assess the relationship between satisfaction with life (SWL), nutritional behaviours, somatic indices, and functional efficiency of senior women. The research was conducted among 120 women aged 60–84 (Me = 65) participating in the “Healthy Active Senior” project at the University of Physical Education in Kraków. The Satisfaction with Life Scale (SWLS) and the proprietary validated questionnaire of nutritional behaviour were used. Body composition was assessed using the method of bioelectrical impedance (TANITA SC-330ST analyser), while physical fitness was evaluated via the Senior Fitness test (Fullerton Functional Fitness Test). Correlations between the variables were measured by implementing Spearman’s R signed-rank correlation coefficients (with p < 0.05). Positive correlations between SWL and selected nutrition behaviours have been demonstrated, including eating 5–6 meals (p < 0.001) and drinking at least 2 litres of fluids a day (p = 0.023), consuming cereal products daily, including whole-grains (p = 0.001), avoiding alcoholic beverages (p = 0.030), and applying vitamin D supplementation (p = 0.010). At the same time, negative correlations between SWL and limiting the consumption of red as well as processed meats (p = 0.002), animal fats (p = 0.046), and the preference for vegetable oils in one’s diet (p = 0.023) were shown. Significant correlations between satisfaction with life and two indicators of functional fitness were also confirmed: negative—with the variable ‘2.44-m Get-Up and Go’ (p = 0.003); and positive—with the ‘2-Minute Step in Place’ test (p = 0.034). The relationships between SWL and somatic indices did not reach the level of statistical significance. Among the women participating in the “Healthy Active Senior” programme, correlations between SWL and rational nutritional behaviours, as well as indices of functional fitness, were found (mostly positive), while the trends in these areas were not fully unambiguous, suggesting the validity of conducting further research.
Determining Work-Rest Schedules for Visual Tasks That Use Optical Head-Mounted Displays Based on Visual Fatigue and Visually Induced Motion Sickness Recovery
Authors: Hsiao Chih-Yu , Kuo Chia-Chen , Liou Yi-An , Wang Mao-Jiun
Published: January 2023

This study aimed to determine work-rest schedules for visual tasks of different lengths by evaluating visual fatigue and visually induced motion sickness (VIMS) using an optical head-mounted display (OHMD). Thirty participants were recruited to perform 15 and 30 min visual tasks using an OHMD. After completing each visual task, participants executed six levels of rest time. Critical flicker fusion frequency (CFF) values, relative electroencephalography indices, and Simulator Sickness Questionnaire (SSQ) scores were collected and analyzed. Results indicated that after completing the 15 and 30 min visual tasks, participants experienced visual fatigue and VIMS. There was no significant difference between baseline CFF values, four electroencephalography relative power index values, and SSQ scores when participants completed a 15 min visual task followed by a 20 min rest and a 30 min visual task followed by a 30 min rest. Based on our results, a 20 min rest for visual fatigue and VIMS recovery after a 15 min visual task on an OHMD and a 25 min rest for visual fatigue and VIMS recovery after a 30 min visual task on an OHMD are recommended. This study suggests a work-rest schedule for OHMDs that can be used as a reference for OHMD user guidelines to reduce visual fatigue and visually induced motion sickness.
Sociodemographic Factors Associated with the Level of Knowledge of Early Postpartum Women about Oral Health Prevention in Infants Aged 0 to 2 Years Old: A Cross-Sectional Study under a Multivariable Analysis
Authors: Gaspar-Damaso Nilda , Ladera-Castañeda Marysela , Córdova-Limaylla Nancy , Briceño-Vergel Gissela , Cervantes-Ganoza Luis , Nicho-Valladares Miriam , Cornejo-Pinto Alberto , Echavarría-Gálvez Alí , Cayo-Rojas César
Published: January 2023

The objective was to evaluate the sociodemographic factors associated with the level of knowledge of early puerperal women about oral health prevention in infants. This cross-sectional and analytical study evaluated 303 early puerperal women from a hospital in the Peruvian capital. A validated 18-question questionnaire was used to measure the level of knowledge. A logistic regression model was used to evaluate the influence of age, marital status, educational level, number of children, monthly income, and having a dentist as a family member. A significance of p < 0.05 was considered. A total of 46.86%, 30.36%, and 22.77% of the puerperal had poor, fair, and good knowledge, respectively. The risk of having poor knowledge was two times higher (OR = 2.43; CI: 1.26–4.70) in early postpartum women aged 18 to 25 years than in those older than 35 years. Early postpartum women with no education, primary and secondary education were 11 times (OR = 11.76; CI: 2.41–57.43), 6 times (OR = 6.61; CI: 1.72–25.45), and 5 times (OR = 5.50; CI: 1.52–19.89), respectively, more likely to have significantly poor knowledge compared to those with university education. In conclusion, only a small minority of early postpartum women had a good knowledge of oral health prevention in infants aged 0 to 2 years. Younger and less educated puerperal were at greater risk of having little knowledge on this topic. Finally, not having basic education was the main risk factor identified.
The Associations of Loneliness and Social Support with Cognitive Impairment among Middle-Aged and Older Individuals with Diabetes
Authors: Cohn-Schwartz Ella , Joshi Rennie , McClure Leslie A.
Published: January 2023

Diabetes mellitus is a chronic disease with significant morbidity and mortality and it is associated with poor cognitive performance in later life. This study seeks to determine the relationship between social support and cognitive function among participants with type 2 diabetes mellitus (T2DM). We used data from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, including participants with T2DM aged 45 and older (n = 4821). We examined different aspects of perceived social support, measured as structural social support (e.g., marital status), functional social support (having a caregiver in case of sickness or disability), and loneliness. We examined cognitive functioning using a six-item screener. Our results indicate that adults who felt lonely for 5–7 days per week had almost double the odds of cognitive impairment compared to those who didn’t feel lonely. These results suggest that among middle-aged and older individuals with T2DM, interventions targeting lonely adults and which aim to reduce loneliness may combat some of the risks of cognitive decline.
Geochemical Characteristics of Rare-Metal, Rare-Dispersed, and Rare-Earth Elements and Depositional Environments in the Shanxi Formation Coal, Huainan Coalfield, Anhui, China
Authors: Wang Weicheng , Zheng Liugen , Wu Zhiwei , Zhang Qian , Chen Xing , Chen Yongchun , Zhang Liqun
Published: January 2023

Coal, being one of the major energy sources for power generation, contains several critical trace elements. There is a growing scarcity and expense of these critical elements as a result of the increased demand and limitation of mining sources. To explore the geochemical characteristics of the rare-metal, rare-dispersed (scattered), and rare-earth elements (TREs) in coal, 25 coal seam samples of the Shanxi Formation in the Huainan coalfield were collected. The major element oxides, minerals, and TREs were analyzed by X-ray fluorescence spectroscopy (XRF), X-ray diffraction (XRD), and inductively coupled plasma-mass spectrometry (ICP-MS). The results revealed that the coal of the Shanxi Formation had ultra-low moisture and low ash yield and was medium–high-volatility with low sulfur content and high calorific value. Concerning minerals, the coal was mainly composed of kaolinite, illite, quartz, calcite, dolomite, and pyrite. Compared with Chinese coal and world hard coal, rare-metal element Li and rare-dispersed element Se were enriched, whereas Ga and Ta were only slightly enriched. The average content of REYs was 51.34 μg/g, which is lower than the average content of REYs in Chinese coal. It has the enrichment characteristics of light REYs. In the vertical direction, the content of most TREs was higher in the roof and floor of the coal seam and the parting, indicating that the sedimentary microenvironment plays an important role in controlling the migration and enrichment of elements. The experimental results of sequential chemical extraction and correlation analysis showed that the TREs in the Shanxi Formation coal mainly exist in a residual and carbonate bound state, and occur in clay minerals and carbonate minerals. The enrichment of Se may be due to its high organic form ratio. The C-value, B content, w(Sr)/w(Ba), and REY geochemical parameters indicated that the Shanxi Formation Coal seam was developed in a transitional, semi-saline, deltaic sedimentary environment. With their development affected by seawater, REYs in coal are greatly supplied by terrigenous clastics. The complex sedimentary environment is an important reason for the varying occurrence states of TREs in the Shanxi Formation coals.
Probing Regional Disparities and Their Characteristics in a Suburb of a Global South Megacity: The Case of Bekasi Regency, Jakarta Metropolitan Region
Authors: Kurnia Adib Ahmad , Rustiadi Ernan , Fauzi Akhmad , Pravitasari Andrea Emma , Ženka Jan
Published: January 2023

The Jakarta metropolitan region (the Jakarta megacity), located in the fourth most populous country in the world (Indonesia), is the largest urban agglomeration in the Global South—continues to grow, especially in its outer suburbs (Bekasi Regency). The governments (Central and Local) tend to implement an urban-biased policy (UBP) to connect Bekasi Regency into global production networks and boost Bekasi Regency’s income. However, previous case studies of China and Vietnam have revealed that the UBP increases economic disparities between urban and rural areas. Therefore, this study probes urban–rural economic disparities and their characteristics at a microregional level (desa/kelurahan) in the Bekasi Regency. The methods applied in this study are geographically weighted regression (GWR), RULT index, and quantitative zoning. The results show that almost all desa/kelurahan in the high poverty (HPv) cluster are rural neighborhoods (desa/kelurahan with rural characteristics). By contrast, only 5% of desa/kelurahan with urban characteristics are HPvs, while the remainder are in the low poverty (LPv) cluster. Rural neighborhoods with HPv tend to have a high percentage of households dependent on agriculture. Thus, empirical results (with a case of a Global South megacity suburb) further support previous evidence that the UBP has caused urban–rural economic disparities.
Salvia plebeia R.Br. and Rosmarinic Acid Attenuate Dexamethasone-Induced Muscle Atrophy in C2C12 Myotubes
Authors: Kim Jae-Yong , Kim Hye Mi , Kim Ji Hoon , Guo Shuo , Lee Do Hyun , Lim Gyu Min , Kim Wondong , Kim Chul Young
Published: January 2023

Skeletal muscle atrophy occurs when protein degradation exceeds protein synthesis and is associated with increased circulating glucocorticoid levels. Salvia plebeia R.Br. (SPR) has been used as herbal remedy for a variety of inflammatory diseases and has various biological actions such as antioxidant and anti-inflammatory activities. However, there are no reports on the effects of SPR and its bioactive components on muscle atrophy. Herein, we investigated the anti-atrophic effect of SPR and rosmarinic acid (RosA), a major compound of SPR, on dexamethasone (DEX)-induced skeletal muscle atrophy in C2C12 myotubes. Myotubes were treated with 10 μM DEX in the presence or absence of SPR or RosA at different concentrations for 24 h and subjected to immunocytochemistry, western blot, and measurements of ROS and ATP levels. SPR and RosA increased viability and inhibited protein degradation in DEX-treated C2C12 myotubes. In addition, RosA promoted the Akt/p70S6K/mTOR pathway and reduced ROS production, and apoptosis. Furthermore, the treatment of RosA significantly recovered SOD activity, autophagy activity, mitochondrial contents, and APT levels in DEX-treated myotubes. These findings suggest that SPR and RosA may provide protective effects against DEX-induced muscle atrophy and have promising potential as a nutraceutical remedy for the treatment of muscle weakness and atrophy.
DeepsmirUD: Prediction of Regulatory Effects on microRNA Expression Mediated by Small Molecules Using Deep Learning
Authors: Sun Jianfeng , Ru Jinlong , Ramos-Mucci Lorenzo , Qi Fei , Chen Zihao , Chen Suyuan , Cribbs Adam P. , Deng Li , Wang Xia
Published: January 2023

Aberrant miRNA expression has been associated with a large number of human diseases. Therefore, targeting miRNAs to regulate their expression levels has become an important therapy against diseases that stem from the dysfunction of pathways regulated by miRNAs. In recent years, small molecules have demonstrated enormous potential as drugs to regulate miRNA expression (i.e., SM-miR). A clear understanding of the mechanism of action of small molecules on the upregulation and downregulation of miRNA expression allows precise diagnosis and treatment of oncogenic pathways. However, outside of a slow and costly process of experimental determination, computational strategies to assist this on an ad hoc basis have yet to be formulated. In this work, we developed, to the best of our knowledge, the first cross-platform prediction tool, DeepsmirUD, to infer small-molecule-mediated regulatory effects on miRNA expression (i.e., upregulation or downregulation). This method is powered by 12 cutting-edge deep-learning frameworks and achieved AUC values of 0.843/0.984 and AUCPR values of 0.866/0.992 on two independent test datasets. With a complementarily constructed network inference approach based on similarity, we report a significantly improved accuracy of 0.813 in determining the regulatory effects of nearly 650 associated SM-miR relations, each formed with either novel small molecule or novel miRNA. By further integrating miRNA–cancer relationships, we established a database of potential pharmaceutical drugs from 1343 small molecules for 107 cancer diseases to understand the drug mechanisms of action and offer novel insight into drug repositioning. Furthermore, we have employed DeepsmirUD to predict the regulatory effects of a large number of high-confidence associated SM-miR relations. Taken together, our method shows promise to accelerate the development of potential miRNA targets and small molecule drugs.
The Sertoli Cell Complement Signature: A Suspected Mechanism in Xenograft Survival
Authors: Washburn Rachel L. , Martinez-Marin Dalia , Korać Ksenija , Sniegowski Tyler , Rodriguez Alexis R. , Chilton Beverly S. , Hibler Taylor , Pruitt Kevin , Bhutia Yangzom D. , Dufour Jannette M.
Published: January 2023

The complement system is an important component of transplant rejection. Sertoli cells, an immune regulatory testicular cell, survive long-term when transplanted across immunological barriers; thus, understanding the mechanisms behind this unique survival would be of great benefit to the transplantation field. This study focused on Sertoli cell inhibition of complement as relevant in xenotransplantation. Neonatal pig Sertoli cells (NPSCs) survived activated human complement in vitro while neonatal pig islet (NPI) aggregates and pig aortic endothelial cell (PAEC) survival were diminished to about 65% and 12%, respectively. PAECs cultured in NPSC-conditioned media and human complement demonstrated a 200% increase in survival suggesting that NPSCs secrete complement-inhibiting substances that confer protection. Bioinformatic and molecular analyses identified 21 complement inhibitors expressed by NPSCs with several significantly increased in NPSCs compared to NPIs or PAECs. Lastly, RNA sequencing revealed that NPSCs express 25 other complement factors including cascade components and receptors. Overall, this study identified the most comprehensive Sertoli cell complement signature to date and indicates that the expression of a variety of complement inhibitors ensures a proper regulation of complement through redundant inhibition points. Understanding the regulation of the complement system should be further investigated for extending xenograft viability.
Cadmium-Induced Proteinuria: Mechanistic Insights from Dose–Effect Analyses
Authors: Satarug Soisungwan , Vesey David A. , Gobe Glenda C.
Published: January 2023

Cadmium (Cd) is a toxic metal that accumulates in kidneys, especially in the proximal tubular epithelial cells, where virtually all proteins in the glomerular ultrafiltrate are reabsorbed. Here, we analyzed archived data on the estimated glomerular filtration rate (eGFR) and excretion rates of Cd (ECd), total protein (EProt), albumin (Ealb), β2-microglobulin (Eβ2M), and α1-microglobulin (Eα1M), which were recorded for residents of a Cd contamination area and a low-exposure control area of Thailand. Excretion of Cd and all proteins were normalized to creatinine clearance (Ccr) as ECd/Ccr and EProt/Ccr to correct for differences among subjects in the number of surviving nephrons. Low eGFR was defined as eGFR ≤ 60 mL/min/1.73 m2, while proteinuria was indicted by EPro/Ccr ≥ 20 mg/L of filtrate. EProt/Ccr varied directly with ECd/Ccr (β = 0.263, p < 0.001) and age (β = 0.252, p < 0.001). In contrast, eGFR values were inversely associated with ECd/Ccr (β = −0.266, p < 0.001) and age (β = −0.558, p < 0.001). At ECd/Ccr > 8.28 ng/L of filtrate, the prevalence odds ratios for proteinuria and low eGFR were increased 4.6- and 5.1-fold, respectively (p < 0.001 for both parameters). Thus, the eGFR and tubular protein retrieval were both simultaneously diminished by Cd exposure. Of interest, ECd/Ccr was more closely correlated with EProt/Ccr (r = 0.507), Eβ2M (r = 0.430), and Eα1M/Ccr (r = 0.364) than with EAlb/Ccr (r = 0.152). These data suggest that Cd may differentially reduce the ability of tubular epithelial cells to reclaim proteins, resulting in preferential reabsorption of albumin.
SOMAscan Proteomics Identifies Novel Plasma Proteins in Amyotrophic Lateral Sclerosis Patients
Authors: Berrone Elena , Chiorino Giovanna , Guana Francesca , Benedetti Valerio , Palmitessa Claudia , Gallo Marina , Calvo Andrea , Casale Federico , Manera Umberto , Favole Alessandra , Crociara Paola , Testori Camilla , Carta Valerio , Tessarolo Carlotta , D’Angelo Antonio , De Marco Giovanni , Caramelli Maria , Chiò Adriano , Casalone Cristina , Corona Cristiano
Published: January 2023

Amyotrophic lateral sclerosis (ALS) is a complex disease characterized by the interplay of genetic and environmental factors for which, despite decades of intense research, diagnosis remains rather delayed, and most therapeutic options fail. Therefore, unravelling other potential pathogenetic mechanisms and searching for reliable markers are high priorities. In the present study, we employ the SOMAscan assay, an aptamer-based proteomic technology, to determine the circulating proteomic profile of ALS patients. The expression levels of ~1300 proteins were assessed in plasma, and 42 proteins with statistically significant differential expression between ALS patients and healthy controls were identified. Among these, four were upregulated proteins, Thymus- and activation-regulated chemokine, metalloproteinase inhibitor 3 and nidogen 1 and 2 were selected and validated by enzyme-linked immunosorbent assays in an overlapping cohort of patients. Following statistical analyses, different expression patterns of these proteins were observed in the familial and sporadic ALS patients. The proteins identified in this study might provide insight into ALS pathogenesis and represent potential candidates to develop novel targeted therapies.
Potential Impact of Non-Steroidal Mineralocorticoid Receptor Antagonists in Cardiovascular Disease
Authors: Rahman Asadur , Jahan Nourin , Rahman Md Tanvir , Nishiyama Akira
Published: January 2023

Inappropriate mineralocorticoid receptor (MR) activation in different cardiovascular cell types has deleterious effects on cardiac remodeling and function. Therefore, MR inhibition is a crucial pharmacological strategy to overcome cardiovascular dysfunction. Despite efficient blockade of MR with steroidal MR antagonists (MRAs), their clinical application is unsatisfactory due to the adverse effects. Newer non-steroidal MRAs with greater potency could be suitable for clinical application, especially in patients with type 2 diabetes mellitus and chronic kidney disease. Although clinical evidence has shown the beneficial effects of non-steroidal MRAs on cardiovascular outcomes in patients with heart failure with reduced ejection fraction, clinical trials are ongoing to evaluate the efficacy of heart failure with preserved ejection fraction. Therefore, comparative pharmacological characterization of non-steroidal MRAs over classic steroidal MRAs is crucial. Here, we summarize the pre-clinical evidence of non-steroidal MRAs, which suggests an improvement in cardiac dysfunction, as well as the underlying molecular mechanisms in animal models mimicking different clinical conditions. In addition, we discuss up-to-date information from clinical trials regarding the beneficial effects of non-steroidal MRAs on meaningful cardiovascular outcomes. Both pre-clinical and clinical evidence support treatment with non-steroidal MRAs in patients with cardiovascular disease.
Opioid-Induced Reductions in Amygdala Lateral Paracapsular GABA Neuron Circuit Activity
Authors: Ronström Joakim W. , Johnson Natalie L. , Jones Stephen T. , Werner Sara J. , Wadsworth Hillary A. , Brundage James N. , Stolp Valerie , Graziane Nicholas M. , Silberman Yuval , Steffensen Scott C. , Yorgason Jordan T.
Published: January 2023

Opioid use and withdrawal evokes behavioral adaptations such as drug seeking and anxiety, though the underlying neurocircuitry changes are unknown. The basolateral amygdala (BLA) regulates these behaviors through principal neuron activation. Excitatory BLA pyramidal neuron activity is controlled by feedforward inhibition provided, in part, by lateral paracapsular (LPC) GABAergic inhibitory neurons, residing along the BLA/external capsule border. LPC neurons express µ-opioid receptors (MORs) and are potential targets of opioids in the etiology of opioid-use disorders and anxiety-like behaviors. Here, we investigated the effects of opioid exposure on LPC neuron activity using immunohistochemical and electrophysiological approaches. We show that LPC neurons, and other nearby BLA GABA and non-GABA neurons, express MORs and δ-opioid receptors. Additionally, DAMGO, a selective MOR agonist, reduced GABA but not glutamate-mediated spontaneous postsynaptic currents in LPC neurons. Furthermore, in LPC neurons, abstinence from repeated morphine-exposure in vivo (10 mg/kg/day, 5 days, 2 days off) decrease the intrinsic membrane excitability, with a ~75% increase in afterhyperpolarization and ~40–50% enhanced adenylyl cyclase-dependent activity in LPC neurons. These data show that MORs in the BLA are a highly sensitive targets for opioid-induced inhibition and that repeated opioid exposure results in impaired LPC neuron excitability.
Distribution of DC Subtypes: CD83+, DC-LAMP+, CD1a+, CD1c+, CD123+, and DC-SIGN+ in the Tumor Microenvironment of Endometrial Cancers—Correlation with Clinicopathologic Features
Authors: Dyduch Grzegorz , Miążek Apolonia , Laskowicz Łukasz , Szpor Joanna
Published: January 2023

Treatment options for endometrial cancer (EC) do not provide satisfactory survival improvement for advanced cases, hence the interest in novel therapies utilizing immunological regulatory mechanisms. Measures to modify the functionality of dendritic cells (DCs) found in TME are intensively investigated, given that DCs play a crucial role in inducing antitumor immunity. Samples of malignant endometrial neoplasms obtained from 94 patients were immunohistochemically stained with selected antibodies. Counts of positively identified DCs were correlated with clinical advancement and histological malignancy of cancers. The most prominent DC subtypes were immature DC-SIGN+ or CD123+. Mature CD83+ DCs were the fewest. We found a significant divergence of grade value distribution between cancers of different DCs’ CD1a+ counts. The DC-LAMP+ count was positively associated with grade. Cancers with the least DC CD1c+ or DC CD123+ had higher pT scores than ones that were more heavily infiltrated. ECs can suppress immune cells, hence the predominance of immature DCs in our samples. Associations between DC counts and clinicopathological features of EC were observed only for a few subsets, which was plausibly due to the low diversity of the obtained samples or the small group size. Predictive abilities of particular DC immune subsets within EC’s TME remain ambiguous, which calls for further research.
Glycoproteomics in Cerebrospinal Fluid Reveals Brain-Specific Glycosylation Changes
Authors: Baerenfaenger Melissa , Post Merel A. , Langerhorst Pieter , Huijben Karin , Zijlstra Fokje , Jacobs Joannes F. M. , Verbeek Marcel M. , Wessels Hans J. C. T. , Lefeber Dirk J.
Published: January 2023

The glycosylation of proteins plays an important role in neurological development and disease. Glycoproteomic studies on cerebrospinal fluid (CSF) are a valuable tool to gain insight into brain glycosylation and its changes in disease. However, it is important to consider that most proteins in CSFs originate from the blood and enter the CSF across the blood–CSF barrier, thus not reflecting the glycosylation status of the brain. Here, we apply a glycoproteomics method to human CSF, focusing on differences between brain- and blood-derived proteins. To facilitate the analysis of the glycan site occupancy, we refrain from glycopeptide enrichment. In healthy individuals, we describe the presence of heterogeneous brain-type N-glycans on prostaglandin H2-D isomerase alongside the dominant plasma-type N-glycans for proteins such as transferrin or haptoglobin, showing the tissue specificity of protein glycosylation. We apply our methodology to patients diagnosed with various genetic glycosylation disorders who have neurological impairments. In patients with severe glycosylation alterations, we observe that heavily truncated glycans and a complete loss of glycans are more pronounced in brain-derived proteins. We speculate that a similar effect can be observed in other neurological diseases where a focus on brain-derived proteins in the CSF could be similarly beneficial to gain insight into disease-related changes.
Gut Microbiota-Derived TMAO: A Causal Factor Promoting Atherosclerotic Cardiovascular Disease?
Authors: Canyelles Marina , Borràs Carla , Rotllan Noemí , Tondo Mireia , Escolà-Gil Joan Carles , Blanco-Vaca Francisco
Published: January 2023

Trimethylamine-N-oxide (TMAO) is the main diet-induced metabolite produced by the gut microbiota, and it is mainly eliminated through renal excretion. TMAO has been correlated with an increased risk of atherosclerotic cardiovascular disease (ASCVD) and related complications, such as cardiovascular mortality or major adverse cardiovascular events (MACE). Meta-analyses have postulated that high circulating TMAO levels are associated with an increased risk of cardiovascular events and all-cause mortality, but the link between TMAO and CVD remains not fully consistent. The results of prospective studies vary depending on the target population and the outcome studied, and the adjustment for renal function tends to decrease or reverse the significant association between TMAO and the outcome studied, strongly suggesting that the association is substantially mediated by renal function. Importantly, one Mendelian randomization study did not find a significant association between genetically predicted higher TMAO levels and cardiometabolic disease, but another found a positive causal relationship between TMAO levels and systolic blood pressure, which—at least in part—could explain the link with renal function. The mechanisms by which TMAO can increase this risk are not clearly elucidated, but current evidence indicates that TMAO induces cholesterol metabolism alterations, inflammation, endothelial dysfunction, and platelet activation. Overall, there is no fully conclusive evidence that TMAO is a causal factor of ASCVD, and, especially, whether TMAO induces or just is a marker of hypertension and renal dysfunction requires further study.
Definition and Characterization of SOX11-Derived T Cell Epitopes towards Immunotherapy of Glioma
Authors: Liu Yibin , Keib Anna , Neuber Brigitte , Wang Lei , Riemer Angelika B. , Bonsack Maria , Hückelhoven-Krauss Angela , Schmitt Anita , Müller-Tidow Carsten , Schmitt Michael
Published: January 2023

The transcription factor SOX11 is a tumor-associated antigen with low expression in normal cells, but overexpression in glioblastoma (GBM). So far, conventional surgery, chemotherapy, and radiotherapy have not substantially improved the dismal prognosis of relapsed/refractory GBM patients. Immunotherapy is considered a promising strategy against GBM, but there is a fervent need for better immunotargets in GBM. To this end, we performed an in silico prediction study on SOX11, which primarily yielded ten promising HLA-A*0201-restricted peptides derived from SOX11. We defined a novel peptide FMACSPVAL, which had the highest score according to in silico prediction (6.02 nM by NetMHC-4.0) and showed an exquisite binding affinity to the HLA-A*0201 molecule in the peptide-binding assays. In the IFN-γ ELISPOT assays, FMACSPVAL demonstrated a high efficiency for generating SOX11-specific CD8+ T cells. Nine out of thirty-two healthy donors showed a positive response to SOX11, as assessed by the ELISPOT assays. Therefore, this novel antigen peptide epitope seems to be promising as a target for T cell-based immunotherapy in GBM. The adoptive transfer of in vitro elicited SOX11-specific CD8+ T cells constitutes a potential approach for the treatment of GBM patients.
Therapeutic Potential of Bioactive Components from Scutellaria baicalensis Georgi in Inflammatory Bowel Disease and Colorectal Cancer: A Review
Authors: Jang Jung Yoon , Im Eunok , Kim Nam Deuk
Published: January 2023

Scutellaria baicalensis Georgi (SBG), an herbal medicine with various biological activities, including anti-inflammatory, anticancer, antiviral, antibacterial, and antioxidant activities, is effective in treatment of colitis, hepatitis, pneumonia, respiratory infections, and allergic diseases. This herbal medicine consists of major active substances, such as baicalin, baicalein, wogonoside, and wogonin. Inflammatory bowel disease (IBD) comprises a group of inflammatory conditions of the colon and small intestine, with Crohn’s disease and ulcerative colitis being the main types. IBD can lead to serious complications, such as increased risk of colorectal cancer (CRC), one of the most common cancers worldwide. Currently, there is no cure for IBD, and its incidence has been increasing over the past few decades. This review comprehensively summarizes the efficacy of SBG in IBD and CRC and may serve as a reference for future research and development of drugs for IBD and cancer treatment.
Effectiveness and Safety of Over-the-Counter Tooth-Whitening Agents Compared to Hydrogen Peroxide In Vitro
Authors: Müller-Heupt Lena Katharina , Wiesmann-Imilowski Nadine , Kaya Sebahat , Schumann Sven , Steiger Maximilian , Bjelopavlovic Monika , Deschner James , Al-Nawas Bilal , Lehmann Karl Martin
Published: January 2023

(1) This study investigated the whitening effect, cytotoxicity and enamel surface alterations induced by different over-the-counter (OTC) bleaching agents in comparison to hydrogen peroxide. (2) Human teeth (n = 60) were randomly assigned into 6 groups (n = 10), stained with coffee solution for 7 d, followed by a whitening period of 7 d with either placebo, bromelain, sodium bicarbonate, sodium chlorite, PAP or hydrogen peroxide. Color measurements were performed with a spectrophotometer. Scanning electron micrographs (SEM) were taken to assess the enamel structure. Cytotoxicity of the tested substances was assessed based on the cell viability of primary human fibroblasts. (3) The application of all whitening gels resulted in a greater color difference of the enamel (ΔE) in comparison to the negative control. Hydrogen peroxide caused the greatest color difference. Bromelain and PAP treatment showed no enamel surface changes, in contrast to hydrogen peroxide treatment, which showed very mild interprismatic dissolution. Bromelain was the only non-cytotoxic agent. (4) The maximum effect achieved by all OTC bleaching agents was the removal of stains, whereas hydrogen peroxide was capable of further whitening the teeth. Bromelain treatment was neither cytotoxic, nor resulted in enamel surface alterations, and its whitening effect was less, yet still effective, compared to hydrogen peroxide.