bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Tobacco Smoking on the Survivability of Patients with Multiple Cancers and Single Lung Cancer
Authors: Romaszko-Wojtowicz Anna , Lorenc Andżelika , Buciński Adam , Doboszyńska Anna
Published: July 2022

Lung cancer is the leading cause of death worldwide among men and women. Tobacco smoking is the number one risk factor for lung cancer. The aim of our study was to evaluate the survivability of patients with single lung cancer in relation to the survival time in patients with multiple neoplasms whose last neoplasm was a lung cancer. A retrospective analysis was con-ducted of data from medical histories of patients hospitalized at the Pulmonary Hospital in Olsztyn (Poland) from 2012 to 2017, with a lung cancer diagnosis as the first or subsequent cancer. The total longevity of women with diagnosed multiple cancers was found to be shorter than that of men: 67.60 years (SD: 7.77) and 69.91 years (SD: 7.97), respectively. Among the ex-smokers, the longevity of men (68.93 years) was longer than that of women (66.18 years). Survival time, counted from the diagnosis of both the first and subsequent cancer, was longer among patients with multiple cancers than among patients with single lung cancer (p = 0.000). Women’s survivability was worse than men’s in the case of multiple cancers and in the group of people who quit smoking (p = 0.037; p = 0.000). To conclude, smoking tobacco affects the survival of patients with lung cancer. Smoking cessation improves overall survival.
Does Tibetan Household Livelihood Capital Enhance Tourism Participation Sustainability? Evidence from China’s Jiaju Tibetan Village
Authors: Shui Wei , Zhang Yiyi , Wang Xinggui , Liu Yuanmeng , Wang Qianfeng , Duan Fei , Wu Chaowei , Shui Wanyu
Published: July 2022

Identifying effective transformations to reduce poverty and approach rural sustainability is at the core of the first sustainable development goal of the United Nations. This article offers scientific support for continued efforts in sustaining rural development and livelihood resilience. Many studies have examined drivers of livelihood transition from farming to non-farm activities, especially participation in tourism against the backdrop of rural tourism development. However, few studies have identified ways to measure the level of tourism participation or have discussed how household-level capital influences decisions regarding tourism participation made by Tibetan ethnic households. This article assesses the role of livelihood capital in the adoption of tourism activities at the household level in Jiaju Tibetan Village, an ethnic region that is experiencing struggling agricultural business and developing tourism sector. Using household survey data, this study presents an ordinal logistic regression model to identify the determinants of the household tourism participation level. The results showed that households’ tourism participation was influenced by physical capital (e.g., proximity to major roads, odds ratio = 2.83 at p = 0.024; fixed capitals, odds ratio = 101.19 at p = 0.039), human capital (e.g., availability of family labor, odds ratio = 0.25 at p = 0.004; availability of skilled member, odds ratio = 2.91 at p = 0.002), and social capital (e.g., relatives in governmental sectors, odds ratio = 5.22 at p = 0.044; government payments, odds ratio = 8.78 at p = 0.04), while the influence of financial capital was not significant. The proximity to major roads, availability of skilled members, fixed assets, and direct and indirect support from the government to households were significantly and positively associated with tourism participation level. The effects of household labor availability and annual family income remain unclear. Overall, household livelihood capital plays a critical role in the enhancement of tourism participation in Jiaju Tibetan Village. Our findings have implications for understanding the shift of on-farm occupation to off-farm activities in tourism and for the pursuit of policies contributing to poverty reduction and rural revitalization in China as well as to the Sustainable Development Goals.
A-REST (Activity to Reduce Excessive Sitting Time): A Feasibility Trial to Reduce Prolonged Sitting in Police Staff
Authors: Brierley Marsha L. , Smith Lindsey R. , Chater Angel M. , Bailey Daniel P.
Published: July 2022

The aim of this study was to evaluate the acceptability and feasibility of a theory-derived sedentary workplace intervention for police office staff. Twenty-four staff participated in an 8-week intervention (single arm, pre-post design) incorporating an education session, team competition with quick response (QR) codes, team trophy, weekly leaderboard newsletters, a self-monitoring phone app, and electronic prompt tools. The intervention supported participants to reduce and break up their sitting time with three minutes of incidental movement every 30 min at work. Feasibility and acceptability were assessed using mixed methods via the RE-AIM QuEST and PRECIS-2 frameworks. The intervention was highly pragmatic in terms of eligibility, organisation, adherence, outcome, and analysis. It was slightly less pragmatic on recruitment and setting. Delivery and follow-up were more explanatory. Reach and adoption indicators demonstrated feasibility among police staff, across a range of departments, who were demographically similar to participants in previous office-based multi-component interventions. The intervention was delivered mostly as planned with minor deviations from protocol (implementation fidelity). Participants perceived the intervention components as highly acceptable. Results showed improvements in workplace sitting and standing, as well as small improvements in weight and positive affect. Evaluation of the intervention in a fully powered randomised controlled trial to assess behaviour and health outcomes is recommended.
Simulation on the Evolution Trend of the Urban Sprawl Spatial Pattern in the Upper Reaches of the Yangtze River, China
Authors: Zhang Yuxiang , Guan Dongjie , He Xiujuan , Yin Boling
Published: July 2022

Urban sprawl has become the main pattern of spatial expansion in many large cities in China, and its ecological and environmental effects profoundly impact Chinese urban development. In this paper, nighttime light data and statistical yearbook data are adopted as basic data sources to simulate the evolution trend of the urban sprawl in the upper Yangtze River (UYR), China. First, the urban sprawl index (USI) is employed to assess the level of urban sprawl and to determine the characteristics of urban sprawl under different scales. Second, the spatial autocorrelation model is applied to reveal the spatial pattern change characteristics of urban sprawl from 1992 to 2015. Third, a scenario analysis model of urban sprawl is constructed to simulate the evolution trend of the urban sprawl under different scenarios. Finally, based on the Geodetector, the influence of factors and factor interactions influencing urban sprawl in different time periods is analyzed. The results yield the following main conclusions: (1) The urban sprawl in the UYR first intensifies and then stabilizes over time. The number of cities with high USI in Sichuan province, medium cities, and Chengdu-Chongqing urban agglomeration increases over time, indicating that urban sprawl is intensifying in these areas. (2) The urban sprawl hot spots experience a pattern transformation process of point-like expansion-point-ring expansion-point-axis expansion-axis radiation. (3) Under the scenarios with different scales, the urban land sprawl in large cities is the highest, accounting for more than 47% of the UYR. Urban land sprawl extent in the Chengdu-Chongqing urban agglomeration is the highest, accounting for more than 51% of the UYR. The cities exhibiting the highest sprawl are Chongqing, Lijiang, and Kunming, accounting for 25.84%, 7.37%, and 5.11%, respectively, of the UYR. (4) In the different time scenario simulations, the urban land in large cities exhibits the highest sprawl, accounting for approximately 48.16% of the UYR. The urban land in the Chengdu-Chongqing urban agglomeration demonstrates the highest sprawl, accounting for 50.92% of the UYR. (5) From 1996 to 2002, the driver with the highest influence on urban sprawl was secondary industry share of GDP, with a q-statistic of 0.616. From 2009 to 2015, the driver with the highest influence on urban sprawl was green space per capita with a q-statistic of 0.396.
The Impact of Mortality Salience, Negative Emotions and Cultural Values on Suicidal Ideation in COVID-19: A Conditional Process Model
Authors: Huang Feng , Li Sijia , Li Dongqi , Yang Meizi , Ding Huimin , Di Yazheng , Zhu Tingshao
Published: July 2022

As suicides incurred by the COVID-19 outbreak keep happening in many countries, researchers have raised concerns that the ongoing pandemic may lead to “a wave of suicides” in society. Suicidal ideation (SI) is a critical factor in conducting suicide intervention and also an important indicator for measuring people’s mental health. Therefore, it is vital to identify the influencing factors of suicidal ideation and its psychological mechanism during the outbreak. Based on the terror management theory, in the present study we conducted a social media big data analysis to explore the joint effects of mortality salience (MS), negative emotions (NE), and cultural values on suicidal ideation in 337 regions on the Chinese mainland. The findings showed that (1) mortality salience was a positive predictor of suicidal ideation, with negative emotions acting as a mediator; (2) individualism was a positive moderator in the first half-path of the mediation model; (3) collectivism was a negative moderator in the first half-path of the mediation model. Our findings not only expand the application of the terror management theory in suicide intervention but provide some insights into post-pandemic mental healthcare. Timely efforts are needed to provide psychological interventions and counseling on outbreak-caused negative emotions in society. Compared with people living in collectivism-prevailing regions, those living in individualism-prevailing regions may be more vulnerable to mortality salience and negative emotions and need more social attention.
A 6-Month Home-Based Functional Electrical Stimulation Program for Foot Drop in a Post-Stroke Patient: Considerations on a Time Course Analysis of Walking Performance
Authors: David Romain , Billot Maxime , Ojardias Etienne , Parratte Bernard , Roulaud Manuel , Ounajim Amine , Louis Frédéric , Meklat Hachemi , Foucault Philippe , Lombard Christophe , Jossart Anne , Mainini Laura , Lavallière Martin , Goudman Lisa , Moens Maarten , Laroche Davy , Salga Marjorie , Genêt François , Daviet Jean-Christophe , Perrochon Anaick , Compagnat Maxence , Rigoard Philippe
Published: July 2022

Foot drop is a common disability in post-stroke patients and represents a challenge for the clinician. To date, ankle foot orthosis (AFO) combined with conventional rehabilitation is the gold standard of rehabilitation management. AFO has a palliative mechanical action without actively restoring the associated neural function. Functional electrical stimulation (FES), consisting of stimulation of the peroneal nerve pathway, represents an alternative approach. By providing an FES device (Bioness L-300, BIONESS, Valencia, CA, USA) for 6 months to a post-stroke 22-year-old woman with a foot drop, our goal was to quantify its potential benefit on walking capacity. The gait parameters and the temporal evolution of the speed were collected with a specific connected sole device (Feet Me®) during the 10-m walking, the time up and go, and the 6-minute walking tests with AFO, FES, or without any device (NO). As a result, the walking speed changes on 10-m were clinically significant with an increase from the baseline to 6 months in AFO (+0.14 m.s−1), FES (+0.36 m.s−1) and NO (+0.32 m.s−1) conditions. In addition, the speed decreased at about 4-min in the 6-minute walking test in NO and AFO conditions, while the speed increased in the FES conditions at baseline and after 1, 3, and 6 months. In addition to the walking performance improvement, monitoring the gait speed in an endurance test after an ecological rehabilitation training program helps to examine the walking performance in post-stroke patients and to propose a specific rehabilitation program.
Evolution Modes, Types, and Social-Ecological Drivers of Ecologically Critical Areas in the Sichuan–Yunnan Ecological Barrier in the Last 15 Years
Authors: Shi Xinyu , Zhao Xiaoqing , Pu Junwei , Huang Pei , Gu Zexian , Chen Yanjun
Published: July 2022

The ecological barrier is a complex ecosystem that couples the human–nature relationship, and the ecologically critical area is an irreplaceable area with a special value in the ecosystem. Therefore, protecting the ecologically critical area is vital for maintaining and improving regional ecological security. Limited research has been conducted on the evolution of ecologically critical areas, and none of the studies have considered the spatiotemporal heterogeneity of the driving factors for different evolution modes and types. Therefore, this research adopts the ecologically critical index, landscape expansion index, and the random forest model to analyze the pattern, driving factors, and its spatial-temporal heterogeneity to the evolution modes and specific types of ecologically critical areas in the Sichuan–Yunnan ecological barrier area in the last 15 years. The results showed that: (1) the ecologically critical areas in the Sichuan–Yunnan ecological barrier have changed dramatically, with the area reduction being 61.06%. Additionally, the spatial distribution characteristics of the ecologically critical area from north to south include planar, point, and linear forms. (2) The evolution trend of the ecologically critical area is ‘degradation–expansion–degradation’. Spread is the predominant type of expansion mode, whereas atrophy is the predominant type of degradation mode, indicating that the evolution mainly occurs at the edge of the original ecologically critical areas. (3) In general, precipitation, area of forest, area of cropland, and GDP have contributed significantly to the evolution of ecologically critical areas. However, the same driving factor has different effects on the expansion and degradation of these areas. Expansion is driven by multiple factors at the same time but is mainly related to human activities and land use change, whereas for degradation, climate and policy are the main driving factors. The present research aimed to quantitatively identify the evolution modes and specific types of ecologically critical areas and explore the spatiotemporal heterogeneity of driving factors. The results can help decision-makers in formulating ecological protection policies according to local conditions and in maintaining and enhancing the regional ecological functions, thereby promoting the sustainable development of society-economy-ecology.
Management of Female Genital Mutilation/Cutting-Related Obstetric Complications: A Training Evaluation
Authors: Nordmann Kim , Subirón-Valera Ana Belén , King Mandella , Küpper Thomas , Martínez-Pérez Guillermo Z.
Published: July 2022

Although female genital mutilation/cutting (FGM/C) is a prevalent practice in Liberia, healthcare workers lack the capacity to provide adequate care for FGM/C survivors. Therefore, Liberian nurses, physician assistants, midwives and trained traditional midwives were trained in sexual, obstetric and psychosocial care for FGM/C survivors in 2019. Through questionnaires, we assessed knowledge acquisition, trainee attitudes towards FGM/C care and acceptability to implement WHO-endorsed recommendations. The questionnaires were analyzed using descriptive statistics for quantitative data and an inductive approach for qualitative data. A total of 99 female and 34 male trainees participated. Most trainees perceived FGM/C as harmful to women’s health, as a violation of women’s rights and showed a willingness to change their clinical practice. While 82.8% (n = 74/90) perceived their role in advocating against FGM/C, 10.0% (n = 9/90) felt that they should train traditional circumcisers to practice FGM/C safely. The pre-training FGM/C knowledge test demonstrated higher scores among physician assistants (13.86 ± 3.02 points) than among nurses (12.11 ± 3.12 points) and midwives (11.75 ± 2.27 points). After the training, the mean test score increased by 1.69 points, from 12.18 (±2.91) points to 13.87 (±2.65) points. The trainings successfully increased theoretical knowledge of FGM/C-caused health effects and healthcare workers’ demonstrated willingness to implement evidence-based guidelines when providing care to FMG/C survivors.
Domain-Specific Language for Land Administration System Transactions
Authors: Pržulj Đorđe , Dejanović Igor , Stefanović Miroslav , Lolić Teodora , Sladojević Srđan
Published: July 2022

The Land Administration System (LAS) records real estates, owners, and rights information. Changes that take place in the real world are recorded as transactions in LAS. This paper discusses various data-integrity constraints that have to be taken into account so that LAS data will be correct and consistent after the execution of LAS transactions. Those transactions are executed by system users, typically through some graphical user interface (GUI) applications. Domain-specific languages (DSLs) provide the possibility for domain experts to write statements that can be interpreted and executed on respective software systems. In the case of LAS, DSL for LAS transactions could enable land administration experts to write statements that would execute transactions and keep LAS data up to date with real world changes. Two types of LAS transactions are considered: legal transactions, which result in ownership changes, and survey transactions, which change the real estate geometry data. In this paper, a possible DSL solution for transactions in the LAS domain is proposed. A system architecture that could enable the efficient writing, validation, verification, execution, and storage of DSL statements is also proposed. A possible DSL for LAS transaction implementation is presented, and examples of legal and survey transactions are explained. The advantages and possible challenges of the proposed solution’s implementation are also discussed in this paper.
Involvement of Molecular Mechanisms between T/B Cells and IL-23: From Palmoplantar Pustulosis to Autoimmune Diseases
Authors: Fukasawa Takemichi , Yoshizaki-Ogawa Asako , Enomoto Atsushi , Miyagawa Kiyoshi , Sato Shinichi , Yoshizaki Ayumi
Published: July 2022

Palmoplantar pustulosis (PPP) is a disease that causes recurrent blisters and aseptic pustules on the palms and soles. It has been suggested that both innate and acquired immunity are involved. In particular, based on the tonsils and basic experiments, it has been assumed that T and B cells are involved in its pathogenesis. In addition, the results of clinical trials have suggested that IL-23 is closely related to the pathogenesis. This review describes PPP and the genetic background, the factors involved in the onset and exacerbation of disease and its relation to the molecular mechanism. In addition, we describe the usefulness of biological therapy and its implications in relation to the importance in pathology, the pathogenesis of PPP, the importance of the role of the IL-23–Th17 axis and IL-36 in PPP. Furthermore, we describe an animal experimental model of PPP, the efficacy and mechanism of action of guselkumab, an anti-IL-23 antibody, the latest research, and finally the possibility for it to be effective for other autoimmune diseases.
Irradiated Triple-Negative Breast Cancer Co-Culture Produces a Less Oncogenic Extracellular Matrix
Authors: Brett Elizabeth , Rosemann Michael , Azimzadeh Omid , Pagani Andrea , Prahm Cosima , Daigeler Adrien , Duscher Dominik , Kolbenschlag Jonas
Published: July 2022

Triple-negative breast cancer is the most common and most deadly cancer among women. Radiation is a mainstay of treatment, administered after surgery, and used in the hope that any remaining cancer cells will be destroyed. While the cancer cell response is normally the focus of radiation therapy, little is known about the tumor microenvironment response after irradiation. It is widely reported that increased collagen expression and deposition are associated with cancer progression and poor prognosis in breast cancer patients. Aside from the classical fibrotic response, ratios of collagen isoforms have not been studied in a radiated tumor microenvironment. Here, we created one healthy co-culture of stromal fibroblasts and adipose-derived stem cells, and one triple-negative breast cancer co-culture, made of stromal fibroblasts, adipose derived stem cells, and triple-negative breast cancer cells. After irradiation, growth and decellularization of co-cultures, we reseeded the breast cancer cells for 24 h and analyzed the samples using mass spectrometry. Proteomic analysis revealed that collagen VI, a highly oncogenic collagen isoform linked to breast cancer, was decreased in the irradiated cancer co-culture. This indicates that the anti-cancer impact of radiation may be not only cell ablative, but also influential in creating a less oncogenic microenvironment.
COX-2/sEH Dual Inhibitor Alleviates Hepatocyte Senescence in NAFLD Mice by Restoring Autophagy through Sirt1/PI3K/AKT/mTOR
Authors: Zhang Chen-Yu , Tan Xiao-Hua , Yang Hui-Hui , Jin Ling , Hong Jie-Ru , Zhou Yong , Huang Xiao-Ting
Published: July 2022

We previously found that the disorder of soluble epoxide hydrolase (sEH)/cyclooxygenase-2 (COX-2)-mediated arachidonic acid (ARA) metabolism contributes to the pathogenesis of the non-alcoholic fatty liver disease (NAFLD) in mice. However, the exact mechanism has not been elucidated. Accumulating evidence points to the essential role of cellular senescence in NAFLD. Herein, we investigated whether restoring the balance of sEH/COX-2-mediated ARA metabolism attenuated NAFLD via hepatocyte senescence. A promised dual inhibitor of sEH and COX-2, PTUPB, was used in our study to restore the balance of sEH/COX-2-mediated ARA metabolism. In vivo, NAFLD was induced by a high-fat diet (HFD) using C57BL/6J mice. In vitro, mouse hepatocytes (AML12) and mouse hepatic astrocytes (JS1) were used to investigate the effects of PTUPB on palmitic acid (PA)-induced hepatocyte senescence and its mechanism. PTUPB alleviated liver injury, decreased collagen and lipid accumulation, restored glucose tolerance, and reduced hepatic triglyceride levels in HFD-induced NAFLD mice. Importantly, PTUPB significantly reduced the expression of liver senescence-related molecules p16, p53, and p21 in HFD mice. In vitro, the protein levels of γH2AX, p53, p21, COX-2, and sEH were increased in AML12 hepatocytes treated with PA, while Ki67 and PCNA were significantly decreased. PTUPB decreased the lipid content, the number of β-gal positive cells, and the expression of p53, p21, and γH2AX proteins in AML12 cells. Meanwhile, PTUPB reduced the activation of hepatic astrocytes JS1 by slowing the senescence of AML12 cells in a co-culture system. It was further observed that PTUPB enhanced the ratio of autophagy-related protein LC3II/I in AML12 cells, up-regulated the expression of Fundc1 protein, reduced p62 protein, and suppressed hepatocyte senescence. In addition, PTUPB enhanced hepatocyte autophagy by inhibiting the PI3K/AKT/mTOR pathway through Sirt1, contributing to the suppression of senescence. PTUPB inhibits the PI3K/AKT/mTOR pathway through Sirt1, improves autophagy, slows down the senescence of hepatocytes, and alleviates NAFLD.
Dosing Limitation for Intra-Renal Arterial Infusion of Mesenchymal Stromal Cells
Authors: Munk Anders , Duvald Christina Søndergaard , Pedersen Michael , Lohmann Stine , Keller Anna Krarup , Møller Bjarne Kuno , Ringgaard Steffen , Buus Niels Henrik , Jespersen Bente , Eijken Marco
Published: July 2022

The immunomodulatory and regenerative properties of mesenchymal stromal cells (MSCs) make MSC therapy a promising therapeutic strategy in kidney disease. A targeted MSC administration via the renal artery offers an efficient delivery method with limited spillover to other organs. Although local administration alleviates safety issues with MSCs in systemic circulation, it introduces new safety concerns in the kidneys. In a porcine model, we employed intra-renal arterial infusion of ten million allogenic adipose tissue-derived MSCs. In order to trigger any potential adverse events, a higher dose (hundred million MSCs) was also included. The kidney function was studied by magnetic resonance imaging after the MSC infusion and again at two weeks post-treatment. The kidneys were assessed by single kidney glomerular filtration rate (skGFR) measurements, histology and inflammation, and fibrosis-related gene expression. None of the measured parameters were affected immediately after the administration of ten million MSCs, but the administration of one hundred million MSCs induced severe adverse events. Renal perfusion was reduced immediately after MSC administration which coincided with the presence of microthrombi in the glomeruli and signs of an instant blood-mediated inflammatory reaction. At two weeks post-treatment, the kidneys that were treated with one hundred million MSCs showed reduced skGFR, signs of tissue inflammation, and glomerular and tubular damage. In conclusions, the intra-renal administration of ten million MSCs is well-tolerated by the porcine kidney. However, higher concentrations (one hundred million MSCs) caused severe kidney damage, implying that very high doses of intra-renally administered MSCs should be undertaken with caution.
Regulation of CD4+ and CD8+ T Cell Biology by Short-Chain Fatty Acids and Its Relevance for Autoimmune Pathology
Authors: Schiweck Carmen , Edwin Thanarajah Sharmili , Aichholzer Mareike , Matura Silke , Reif Andreas , Vrieze Elske , Weigert Andreas , Visekruna Alexander
Published: July 2022

The gut microbiota encodes a broad range of enzymes capable of synthetizing various metabolites, some of which are still uncharacterized. One well-known class of microbiota-derived metabolites are the short-chain fatty acids (SCFAs) such as acetate, propionate, butyrate and valerate. SCFAs have long been considered a mere waste product of bacterial metabolism. Novel results have challenged this long-held dogma, revealing a central role for microbe-derived SCFAs in gut microbiota-host interaction. SCFAs are bacterial signaling molecules that act directly on host T lymphocytes by reprogramming their metabolic activity and epigenetic status. They have an essential biological role in promoting differentiation of (intestinal) regulatory T cells and in production of the anti-inflammatory cytokine interleukin-10 (IL-10). These small molecules can also reach the circulation and modulate immune cell function in remote tissues. In experimental models of autoimmune and inflammatory diseases, such as inflammatory bowel disease, multiple sclerosis or diabetes, a strong therapeutic potential of SCFAs through the modulation of effector T cell function was observed. In this review, we discuss current research activities toward understanding a relevance of microbial SCFA for treating autoimmune and inflammatory pathologies from in vitro to human studies.
Exploring the Molecular Interactions of Symmetrical and Unsymmetrical Selenoglycosides with Human Galectin-1 and Galectin-3
Authors: Pirone Luciano , Nieto-Fabregat Ferran , Di Gaetano Sonia , Capasso Domenica , Russo Rita , Traboni Serena , Molinaro Antonio , Iadonisi Alfonso , Saviano Michele , Marchetti Roberta , Silipo Alba , Pedone Emilia
Published: July 2022

Galectins (Gals) are small cytosolic proteins that bind β-galactoside residues via their evolutionarily conserved carbohydrate recognition domain. Their dysregulation has been shown to be associated with many diseases. Consequently, targeting galectins for clinical applications has become increasingly relevant to develop tailored inhibitors selectively for one galectin. Accordingly, binding studies providing the molecular details of the interaction between galectin and inhibitor may be useful for the rational design of potent and selective antagonists. Gal-1 and Gal-3 are among the best-studied galectins, mainly for their roles in cancer progression; therefore, the molecular details of their interaction with inhibitors are demanded. This work gains more value by focusing on the interaction between Gal-1 and Gal-3 with the selenylated analogue of the Gal inhibitor thiodigalactose, characterized by a selenoglycoside bond (SeDG), and with unsymmetrical diglycosyl selenides (unsym(Se). Gal-1 and Gal-3 were produced heterologously and biophysically characterized. Interaction studies were performed by ITC, NMR spectroscopy, and MD simulation, and thermodynamic values were discussed and integrated with spectroscopic and computational results. The 3D complexes involving SeDG when interacting with Gal-1 and Gal-3 were depicted. Overall, the collected results will help identify hot spots for the design of new, better performing, and more specific Gal inhibitors.
BPA Decreases PDCD4 in Bovine Granulosa Cells Independently of miR-21 Inhibition
Authors: Sabry Reem , Williams Makenna , Werry Nicholas , LaMarre Jonathan , Favetta Laura A.
Published: July 2022

microRNAs (miRNAs) are susceptible to environmental factors that might affect cellular function and impose negative effects on female reproduction. miR-21 is the most abundant miRNA in bovine granulosa cells and is widely reported as affected by Bisphenol A (BPA) exposure, yet the cause and consequences are not entirely elucidated. BPA is a synthetic endocrine disruptor associated with poor fertility. miR-21 function in bovine granulosa cells is investigated utilizing locked nucleic acid (LNA) oligonucleotides to suppress miR-21. Before measuring apoptosis and quantifying miR-21 apoptotic targets PDCD4 and PTEN, transfection was optimized and validated. BPA was introduced to see how it affects miR-21 regulation and which BPA-mediated effects are influenced by miR-21. miR-21 knockdown and specificity against additional miRNAs were confirmed. miR-21 was found to have antiapoptotic effects, which could be explained by its effect on the proapoptotic target PDCD4, but not PTEN. Previous findings of miR-21 overexpression were validated using BPA treatments, and the temporal influence of BPA on miR-21 levels was addressed. Finally, BPA effects on upstream regulators, such as VMP1 and STAT3, explain the BPA-dependent upregulation of miR-21 expression. Overall, this research enhances our understanding of miR-21 function in granulosa cells and the mechanisms of BPA-induced reproductive impairment.
Associations of Dynapenic Obesity and Sarcopenic Obesity with the Risk of Complications in COVID-19
Authors: Pérez-Campos Mayoral Laura , Matias-Cervantes Carlos Alberto , Pérez-Campos Eduardo , Romero Díaz Carlos , Laguna Barrios Luis Ángel , Pina Canseco María del Socorro , Martínez Cruz Margarito , Pérez-Campos Mayoral Eduardo , Solórzano Mata Carlos Josué , Rodal Canales Francisco Javier , Martínez Ruíz Héctor , Hernández-Huerta María Teresa
Published: July 2022

Ageing is associated with changes in body composition, such as low muscle mass (sarcopenia), decreased grip strength or physical function (dynapenia), and accumulation of fat mass. When the accumulation of fat mass synergistically accompanies low muscle mass or reduced grip strength, it results in sarcopenic obesity and dynapenic obesity, respectively. These types of obesity contribute to the increased risk of cardiovascular disease and mortality in the elderly, which could increase the damage caused by COVID-19. In this review, we associated factors that could generate a higher risk of COVID-19 complications in dynapenic obesity and sarcopenic obesity. For example, skeletal muscle regulates the expression of inflammatory cytokines and supports metabolic stress in pulmonary disease; hence, the presence of dynapenic obesity or sarcopenic obesity could be related to a poor prognosis in COVID-19 patients.
Toxicogenomics and Molecular Markers in Pollution
Authors: Crespo-Lopez Maria Elena
Published: July 2022

Pollution is defined as the presence in or introduction of a substance into the environment that has harmful or poisonous effects [...]
Dysregulation of SIRT3 SUMOylation Confers AML Chemoresistance via Controlling HES1-Dependent Fatty Acid Oxidation
Authors: Zhang Yirong , Shen Yajie , Wei Weiqing , Wang Wenhan , Jiang Daiji , Ren Yizhuo , Peng Zijing , Fan Qiuju , Cheng Jinke , Ma Jiao
Published: July 2022

Sirtuin 3 (SIRT3) deacetylase is a key regulator for chemoresistance in acute myeloid leukemia (AML) cells due to its capability of modulating mitochondrial metabolism and reactive oxygen species (ROS). SIRT3 is de-SUMOylated by SUMO-specific peptidase 1 (SENP1), which enhances its deacetylase activity. Therefore, dysregulation of SIRT3 SUMOylation may lead to fortified chemoresistance in AML. Indeed, SIRT3 de-SUMOylation was induced by chemotherapeutic agents, which in turn, exacerbated resistance against chemotherapies in AML by activating SIRT3 via preventing its proteasome degradation. Furthermore, RNA-seq revealed that expression of a collection of genes was altered by SIRT3 de-SUMOylation including inhibition of transcription factor Hes Family BHLH Transcription Factor 1 (HES1), a downstream substrate of Notch1 signaling pathway, leading to increased fatty acids oxidation (FAO). Moreover, the SENP1 inhibitor momordin-Ic or HES1 overexpression synergized with cytarabine to eradicate AML cells in vitro and in xenograft mouse models. In summary, the current study revealed a novel role of SIRT3 SUMOylation in the regulation of chemoresistance in AML via HES1-dependent FAO and provided a rationale for SIRT3 SUMOylation and FAO targeted interventions to improve chemotherapies in AML.
The Vascular Endothelium and Coagulation: Homeostasis, Disease, and Treatment, with a Focus on the Von Willebrand Factor and Factors VIII and V
Authors: De Pablo-Moreno Juan A. De , Serrano Luis Javier , Revuelta Luis , Sánchez María José , Liras Antonio
Published: July 2022

The vascular endothelium has several important functions, including hemostasis. The homeostasis of hemostasis is based on a fine balance between procoagulant and anticoagulant proteins and between fibrinolytic and antifibrinolytic ones. Coagulopathies are characterized by a mutation-induced alteration of the function of certain coagulation factors or by a disturbed balance between the mechanisms responsible for regulating coagulation. Homeostatic therapies consist in replacement and nonreplacement treatments or in the administration of antifibrinolytic agents. Rebalancing products reestablish hemostasis by inhibiting natural anticoagulant pathways. These agents include monoclonal antibodies, such as concizumab and marstacimab, which target the tissue factor pathway inhibitor; interfering RNA therapies, such as fitusiran, which targets antithrombin III; and protease inhibitors, such as serpinPC, which targets active protein C. In cases of thrombophilia (deficiency of protein C, protein S, or factor V Leiden), treatment may consist in direct oral anticoagulants, replacement therapy (plasma or recombinant ADAMTS13) in cases of a congenital deficiency of ADAMTS13, or immunomodulators (prednisone) if the thrombophilia is autoimmune. Monoclonal-antibody-based anti-vWF immunotherapy (caplacizumab) is used in the context of severe thrombophilia, regardless of the cause of the disorder. In cases of disseminated intravascular coagulation, the treatment of choice consists in administration of antifibrinolytics, all-trans-retinoic acid, and recombinant soluble human thrombomodulin.
Roles of RNA Sensors in Host Innate Response to Influenza Virus and Coronavirus Infections
Authors: Li Wei , Wang Hongnuan , Zheng Shijun J.
Published: July 2022

Influenza virus and coronavirus are two important respiratory viruses, which often cause serious respiratory diseases in humans and animals after infection. In recent years, highly pathogenic avian influenza virus (HPAIV) and SARS-CoV-2 have become major pathogens causing respiratory diseases in humans. Thus, an in-depth understanding of the relationship between viral infection and host innate immunity is particularly important to the stipulation of effective control strategies. As the first line of defense against pathogens infection, innate immunity not only acts as a natural physiological barrier, but also eliminates pathogens through the production of interferon (IFN), the formation of inflammasomes, and the production of pro-inflammatory cytokines. In this process, the recognition of viral pathogen-associated molecular patterns (PAMPs) by host pattern recognition receptors (PRRs) is the initiation and the most important part of the innate immune response. In this review, we summarize the roles of RNA sensors in the host innate immune response to influenza virus and coronavirus infections in different species, with a particular focus on innate immune recognition of viral nucleic acids in host cells, which will help to develop an effective strategy for the control of respiratory infectious diseases.
Microglia as Therapeutic Target for Radiation-Induced Brain Injury
Authors: Liu Qun , Huang Yan , Duan Mengyun , Yang Qun , Ren Boxu , Tang Fengru
Published: July 2022

Radiation-induced brain injury (RIBI) after radiotherapy has become an increasingly important factor affecting the prognosis of patients with head and neck tumor. With the delivery of high doses of radiation to brain tissue, microglia rapidly transit to a pro-inflammatory phenotype, upregulate phagocytic machinery, and reduce the release of neurotrophic factors. Persistently activated microglia mediate the progression of chronic neuroinflammation, which may inhibit brain neurogenesis leading to the occurrence of neurocognitive disorders at the advanced stage of RIBI. Fully understanding the microglial pathophysiology and cellular and molecular mechanisms after irradiation may facilitate the development of novel therapy by targeting microglia to prevent RIBI and subsequent neurological and neuropsychiatric disorders.
Metabolic Inflexibility as a Pathogenic Basis for Atrial Fibrillation
Authors: Qin Xinghua , Zhang Yudi , Zheng Qiangsun
Published: July 2022

Atrial fibrillation (AF), the most common sustained arrhythmia, is closely intertwined with metabolic abnormalities. Recently, a metabolic paradox in AF pathogenesis has been suggested: under different forms of pathogenesis, the metabolic balance shifts either towards (e.g., obesity and diabetes) or away from (e.g., aging, heart failure, and hypertension) fatty acid oxidation, yet they all increase the risk of AF. This has raised the urgent need for a general consensus regarding the metabolic changes that predispose patients to AF. “Metabolic flexibility” aptly describes switches between substrates (fatty acids, glucose, amino acids, and ketones) in response to various energy stresses depending on availability and requirements. AF, characterized by irregular high-frequency excitation and the contraction of the atria, is an energy challenge and triggers a metabolic switch from preferential fatty acid utilization to glucose metabolism to increase the efficiency of ATP produced in relation to oxygen consumed. Therefore, the heart needs metabolic flexibility. In this review, we will briefly discuss (1) the current understanding of cardiac metabolic flexibility with an emphasis on the specificity of atrial metabolic characteristics; (2) metabolic heterogeneity among AF pathogenesis and metabolic inflexibility as a common pathological basis for AF; and (3) the substrate-metabolism mechanism underlying metabolic inflexibility in AF pathogenesis.
Antipsychotic Drug Aripiprazole Protects Liver Cells from Oxidative Stress
Authors: Kramar Barbara , Pirc Marolt Tinkara , Monsalve Maria , Šuput Dušan , Milisav Irina
Published: July 2022

Antipsychotics used to treat schizophrenia can cause drug-induced liver injury (DILI), according to the Roussel Uclaf Causality Assessment Method. The role of oxidative stress in triggering injury in these DILI cases is unknown. We repeatedly administrated two second-generation antipsychotics, aripiprazole and olanzapine, at laboratory alert levels to study underlying mechanisms in stress prevention upon acute oxidative stress. The drugs were administered continuously for up to 8 weeks. For this, hepatoma Fao cells, which are suitable for metabolic studies, were used, as the primary hepatocytes survive in the culture only for about 1 week. Four stress responses—the oxidative stress response, the DNA damage response and the unfolded protein responses in the endoplasmic reticulum and mitochondria—were examined in H2O2-treated cells by antioxidant enzyme activity measurements, gene expression and protein quantification. Oxidant conditions increased the activity of antioxidant enzymes and upregulated genes and proteins associated with oxidative stress response in aripiprazole-treated cells. While the genes associated with DNA damage response, Gadd45 and p21, were upregulated in both aripiprazole- and olanzapine-treated cells, only aripiprazole treatment was associated with upregulation in response to even more H2O2, which also coincided with better survival. Endoplasmic reticulum stress-induced Chop was also upregulated; however, neither endoplasmic reticulum nor mitochondrial unfolded protein response was activated. We conclude that only aripiprazole, but not olanzapine, protects liver cells against oxidative stress. This finding could be relevant for schizophrenia patients with high-oxidative-stress-risk lifestyles and needs to be validated in vivo.
A Review of Microfluidic Experimental Designs for Nanoparticle Synthesis
Authors: Niculescu Adelina-Gabriela , Mihaiescu Dan Eduard , Grumezescu Alexandru Mihai
Published: July 2022

Microfluidics is defined as emerging science and technology based on precisely manipulating fluids through miniaturized devices with micro-scale channels and chambers. Such microfluidic systems can be used for numerous applications, including reactions, separations, or detection of various compounds. Therefore, due to their potential as microreactors, a particular research focus was noted in exploring various microchannel configurations for on-chip chemical syntheses of materials with tailored properties. Given the significant number of studies in the field, this paper aims to review the recently developed microfluidic devices based on their geometry particularities, starting from a brief presentation of nanoparticle synthesis and mixing within microchannels, further moving to a more detailed discussion of different chip configurations with potential use in nanomaterial fabrication.
Pharmacological Probes to Validate Biomarkers for Analgesic Drug Development
Authors: van Niel Johannes , Bloms-Funke Petra , Caspani Ombretta , Cendros Jose Maria , Garcia-Larrea Luis , Truini Andrea , Tracey Irene , Chapman Sonya C. , Marco-Ariño Nicolás , Troconiz Iñaki F. , Phillips Keith , Finnerup Nanna Brix , Mouraux André , Treede Rolf-Detlef
Published: July 2022

There is an urgent need for analgesics with improved efficacy, especially in neuropathic and other chronic pain conditions. Unfortunately, in recent decades, many candidate analgesics have failed in clinical phase II or III trials despite promising preclinical results. Translational assessment tools to verify engagement of pharmacological targets and actions on compartments of the nociceptive system are missing in both rodents and humans. Through the Innovative Medicines Initiative of the European Union and EFPIA, a consortium of researchers from academia and the pharmaceutical industry was established to identify and validate a set of functional biomarkers to assess drug-induced effects on nociceptive processing at peripheral, spinal and supraspinal levels using electrophysiological and functional neuroimaging techniques. Here, we report the results of a systematic literature search for pharmacological probes that allow for validation of these biomarkers. Of 26 candidate substances, only 7 met the inclusion criteria: evidence for nociceptive system modulation, tolerability, availability in oral form for human use and absence of active metabolites. Based on pharmacokinetic characteristics, three were selected for a set of crossover studies in rodents and healthy humans. All currently available probes act on more than one compartment of the nociceptive system. Once validated, biomarkers of nociceptive signal processing, combined with a pharmacometric modelling, will enable a more rational approach to selecting dose ranges and verifying target engagement. Combined with advances in classification of chronic pain conditions, these biomarkers are expected to accelerate analgesic drug development.
Fine Mapping of qTGW7b, a Minor Effect QTL for Grain Weight in Rice (Oryza sativa L.)
Authors: Gu Houwen , Zhang Kunming , Gull Sadia , Chen Chuyan , Ran Jinhui , Zou Bingyin , Wang Ping , Liang Guohua
Published: July 2022

Grain weight is a key trait that determines rice quality and yield, and it is primarily controlled by quantitative trait loci (QTL). Recently, attention has been paid to minor QTLs. A minor effect QTL qTGW7 that controls grain weight was previously identified in a set of chromosomal fragment substitution lines (CSSLs) derived from Nipponbare (NPB)/93-11. Compared to NPB, the single segment substitution line (SSSL) N83 carrying the qTGW7 introgression exhibited an increase in grain length and width and a 4.5% increase in grain weight. Meanwhile, N83 was backcrossed to NPB to create a separating population, qTGW7b, a QTL distinct from qTGW7, which was detected between markers G31 and G32. Twelve near-isogenic lines (NILs) from the BC9F3 population and progeny of five NILs from the BC9F3:4 population were genotyped and phenotyped, resulting in the fine mapping of the minor effect QTL qTGW7b to the approximately 86.2-kb region between markers G72 and G32. Further sequence comparisons and expression analysis confirmed that five genes, including Os07g39370, Os07g39430, Os07g39440, Os07g39450, and Os07g39480, were considered as the candidate genes underlying qTGW7b. These results provide a crucial foundation for further cloning of qTGW7b and molecular breeding design in rice.
Obesity and Bone Health: A Complex Relationship
Authors: Piñar-Gutierrez Ana , García-Fontana Cristina , García-Fontana Beatriz , Muñoz-Torres Manuel
Published: July 2022

Recent scientific evidence has shown an increased risk of fractures in patients with obesity, especially in those with a higher visceral adipose tissue content. This contradicts the old paradigm that obese patients were more protected than those with normal weight. Specifically, in older subjects in whom there is a redistribution of fat from subcutaneous adipose tissue to visceral adipose tissue and an infiltration of other tissues such as muscle with the consequent sarcopenia, obesity can accentuate the changes characteristic of this age group that predisposes to a greater risk of falls and fractures. Other factors that determine a greater risk in older subjects with obesity are chronic proinflammatory status, altered adipokine secretion, vitamin D deficiency, insulin resistance and reduced mobility. On the other hand, diagnostic tests may be influenced by obesity and its comorbidities as well as by body composition, and risk scales may underestimate the risk of fractures in these patients. Weight loss with physical activity programs and cessation of high-fat diets may reduce the risk. Finally, more research is needed on the efficacy of anti-osteoporotic treatments in obese patients.