bluuebunny/crossref_metadata_2025 huggingface dataset:
Scarcity Value Assessment of Ecosystem Services Based on Changes in Supply and Demand: A Case Study of the Yangtze River Delta City Cluster, China
Authors: Zhou Xiaoping , Yang Lan , Gu Xiaokun , Zhang Lufa , Li Li
Published: September 2022

Rapid urbanization and economic development have resulted in a mismatch between the supply and demand of ecosystem services. The theoretical value of ecosystem services (ESTV) is not suitable for determining ecosystem service compensation, posing challenges for integrated regional ecological development. A scarcity value model was used to analyze the influence of changes in supply and demand on the scarcity value of ecosystem services (ESSV) in the context of land-use change. The spatio-temporal distribution characteristics and trends of the ESSV from 2010 to 2020 were assessed in the Yangtze River Delta (YRD) urban agglomeration in China, and the driving factors were analyzed to provide theoretical guidance for horizontal ecological compensation across regions. The results show the following: (1) In the scenario that did not consider the impact of supply and demand changes on the scarcity value, the total ESTV decreased by 8.67% from 2010 to 2020, and high-value areas shifted to the west and south, whereas low-value areas shifted to the central and northern region and the Jiangsu, Zhejiang, and Shanghai Ringbelt. The ESTV was low in Shanghai and Jiangsu and high in Zhejiang. (2) In the scenario that considered changes in the supply and demand of ecosystem services, the ESSV increased from RMB 213 million in 2010 to RMB 1.323 billion in 2020; an increase of 521.13%. The scarcity value showed high variability within the provinces, with a larger difference between Zhejiang and Jiangsu and a smaller difference between Anhui and Shanghai. The ESSV was higher in counties with increased urbanization and high population density and lower in counties with slower economic growth and fewer people. (3) Regional ecological integration planning and management should be strengthened, and the ESSV might be considered as the reference standard for ecological compensation. The ESSV showed that spatio-temporal heterogeneity might guide the conversion from ecological resources to ecological capital and promote the regulatory role of market mechanisms to achieve horizontal payments for ecosystem services across regions.
Health Risk Assessment of Heavy Metals in Shallow Groundwater of Coal–Poultry Farming Districts
Authors: Chen Jiayu , Gui Herong , Guo Yan , Li Jun
Published: September 2022

This study aimed to assess the heavy metal (Mn, Ni, Cu, Zn, Sr, Cd, Pb, and Cr) pollution characteristics, sources, and human health risks in shallow groundwater in the impact zones of urban and rural semi-intensive poultry farms in Suzhou City. Ordinary kriging interpolation showed that poultry farming contributed substantially to the pollution of shallow groundwater by Mn, Zn, and Cu. Positive matrix factorization was applied to identify the sources of heavy metals, and the health risks were assessed based on the hazard index and carcinogenic risks of the various sources. Heavy metal enrichment was closely related to anthropogenic activities. In addition, four sources were identified: poultry manure (29.33%), natural source (27.94%), industrial activities (22.29%), and poultry wastewater (20.48%). The main exposure route of carcinogenic and non-carcinogenic risks to adults and children was oral ingestion. The non-carcinogenic risk of oral ingestion in children was higher than that in adults; the carcinogenic risk was higher in adults than in children. Poultry manure (42.0%) was considered the largest contributor to non-carcinogenic risk, followed by poultry wastewater (21%), industrial activities (20%), and natural sources (17%). Industrial activity (44%) was the primary contributor to carcinogenic risk, followed by poultry wastewater (25%), poultry manure (19%), and natural sources (12%).
Capturing Household Structure and Mobility within and between Remote Aboriginal Communities in Northern Australia Using Longitudinal Data: A Pilot Study
Authors: Goldsmith Jessie J. , Campbell Patricia T. , Villanueva-Cabezas Juan Pablo , Chisholm Rebecca H. , McKinnon Melita , Gurruwiwi George G. , Dhurrkay Roslyn G. , Dockery Alfred M. , Geard Nicholas , Tong Steven Y. C. , McVernon Jodie , Gibney Katherine B.
Published: September 2022

Cultural practices and development level can influence a population’s household structures and mixing patterns. Within some populations, households can be organized across multiple dwellings. This likely affects the spread of infectious disease through these communities; however, current demographic data collection tools do not record these data. Methods: Between June and October 2018, the Contact And Mobility Patterns in remote Aboriginal Australian communities (CAMP-remote) pilot study recruited Aboriginal mothers with infants in a remote northern Australian community to complete a monthly iPad-based contact survey. Results: Thirteen mother–infant pairs (participants) completed 69 study visits between recruitment and the end of May 2019. Participants reported they and their other children slept in 28 dwellings during the study. The median dwelling occupancy, defined as people sleeping in the same dwelling on the previous night, was ten (range: 3.5–25). Participants who completed at least three responses (n = 8) slept in a median of three dwellings (range: 2–9). Each month, a median of 28% (range: 0–63%) of the participants travelled out of the community. Including these data in disease transmission models amplified estimates of infectious disease spread in the study community, compared to models parameterized using census data. Conclusions: The lack of data on mixing patterns in populations where households can be organized across dwellings may impact the accuracy of infectious disease models for these communities and the efficacy of public health actions they inform.
Role of Atmospheric Temperature and Seismic Activity in Spring Water Hydrogeochemistry in Urumqi, China
Authors: Zhou Zhihua , Zhong Jun
Published: September 2022

Springs offer insight into the sources and mechanisms of groundwater recharge and can be used to characterize fluid migration during earthquakes. However, few reports provide sufficient annual hydrochemical and isotopic data to compare the variation characteristics and mechanisms with both atmospheric temperature and seismic effects. In this study, we used continuous δ2H, δ18O, and major ion data from four springs over 1 year to understand the groundwater origin, recharge sources, circulation characteristics, and coupling relationships with atmospheric temperature and earthquakes. We found that (1) atmospheric temperatures above and below 0 °C can cause significant changes in ion concentrations and water circulation depth, resulting in the mixing of fresh and old water in the aquifer, but it cannot cause changes in δ2H and δ18O. (2) Earthquakes of magnitude ≥ 4.8 within a 66 km epicentral distance can alter fault zone characteristics (e.g., permeability) and aggravate water–rock reactions, resulting in significant changes in δ2H, δ18O, and hydrochemical ion concentrations. (3) Hydrogen and oxygen isotopes are the most sensitive precursory seismic indicators. The results of this study offer a reference for the establishment of long-term hydrochemical and isotopic monitoring, with the potential for use in earthquake forecasting.
Peri-Implant Health and Diagnostic Considerations
Authors: Mancini Leonardo
Published: September 2022

In recent years, implant rehabilitation has become a popular method for replacing lost teeth [...]
Considering the Subjective Well-Being of Israeli Jews during the COVID-19 Pandemic: Messaging Insights from Religiosity and Spirituality as Coping Mechanisms
Authors: Muralidharan Sidharth , Roth-Cohen Osnat , LaFerle Carrie
Published: September 2022

Consistent with Terror Management Theory (TMT), COVID-19 has made us question our mortality and past studies have indicated the importance of religiosity to enhance subjective well-being (SWB), however, studies on spirituality’s impact are incomplete. The pandemic has created an environment where both religiosity and spirituality may play a vital role. Israel was selected due to the emergence of Jewish spirituality, a phenomenon that is growing in importance but understudied. In response to these caveats, the current study examines the mediating role played by spirituality on the SWB of the religious during the pandemic. Participants from Israel (n = 138) were recruited via Qualtrics’ online panels. Findings showed Jews’ religiosity was important to enhance their SWB, i.e., religious beliefs bring certainty and happiness to one’s life, especially, during the COVID-19 pandemic. More importantly, spirituality mediated the effect of religiosity on SWB, specifically, spirituality was important to enhance the well-being of low religious Jews. Implications for health messaging during a global pandemic are discussed.
Assessment of Mental Health and Quality of Life Status of Undergraduate Students in Indonesia during COVID-19 Outbreak: A Cross-Sectional Study
Authors: Karuniawati Hidayah , Sari Nila , Hossain Md. Sanower , Ismail Wan Ismahanisa , Haq Aniq Hudiyah Bil , Yulianti Tri , Taufik Taufik , Sudarsono Gardhika Rizky
Published: September 2022

The COVID-19 pandemic globally impacted physical, spiritual, and mental health (MH). The consequences significantly affected students’ quality of life (QoL) too. This cross-sectional study assessed MH status and its relationship to the QoL of college students in Indonesia. This study collected data (September 2021–April 2022) online using the depression, anxiety, and stress scale-21 (DASS-21) to measure MH and the world health organization quality-of-life scale (WHOQoL-BREF) to measure the QoL. The data were analysed using SPSS with a bivariate and multivariate linear regression test. A total of 606 respondents participated in this study, with the majority being women (81.0%), aged 21–27 years (44.3%), and unmarried (98.5%) respondents. We observed 24.4% (n = 148) moderate depression, 18.3% (n = 111) very severe anxiety, and 21.1% (n = 128) moderate stress status. The QoL measurement determined that a moderate QoL in the physical and environmental health domains (>70%) and poor QoL in the psychological health domain (58.3%) were found. Gender, age, family support, history of COVID-19 diagnosis, family with COVID-19 diagnosis, vaccination status, and physical symptoms are significantly associated with MH status and QoL (p-value < 0.05). This study demonstrated that COVID-19 was negatively related to college students’ MH and QoL. Targeted interventions may be needed to ameliorate both MH and QoL.
The Development and Acceptability of a Wilderness Programme to Support the Health and Well-Being of Adolescent and Young Adult Cancer Survivors: The WAYA Programme
Authors: Jong Miek C. , Stub Trine , Mulder Eric , Jong Mats
Published: September 2022

Detailed descriptions of theory, structure, and activities with causal links to specified outcomes of wilderness programs are lacking. Addressing this gap, the present qualitative study gives a thorough description of the development of the Wilderness programme for Adolescent and Young Adult (AYA) cancer survivors (WAYA). WAYA is adapted to the individual needs of AYA cancer survivors. It was conceived around Næss’s ecosophy and the Positive Health Model, and refined based on findings from a scoping review and patient/public involvement. Programme aims were to increase physical activity, self-confidence, personal growth, joy, safety within nature, meaningful relationships, and self-efficacy. The programme was an eight-day expedition followed three months later by a four-day base-camp. Activities included hiking, backpacking, kayaking, rock climbing, mindfulness and bushcrafting. Evaluation of the programme through focus group and individual interviews with 15 facilitators and 17 participants demonstrated that a diverse group of participants, challenging activities, and mindfulness-based practices were found to positively influence group bonding and the learning process. Furthermore, including an expedition and base-camp component was found to be beneficial in supporting the development of participants’ own personal outdoor practices. In conclusion, this study demonstrated that the WAYA programme is safe and well accepted by AYA cancer survivors.
Can Global Value Chain Participation Drive Green Upgrade in China’s Manufacturing Industry?
Authors: Wang Shi , Wang Hua
Published: September 2022

Engagement in the global division of labor has greatly influenced China’s economy and environment. With the multi-regional input–output (MRIO) framework, we calculate the global value chain (GVC) participation index of China’s 16 manufacturing sectors. We also measure the green upgrade index of manufacturing sectors based on the super-efficiency epsilon-based measure (SEBM) and the Malmquist–Luenberger (ML) index. In addition, the effect of GVC participation on the green upgrade of manufacturing sectors is empirically tested with a fixed effects regression model for panel data. Results show that: (1) sectors that rank high in the forward linkage-based GVC participation index also tend to rank high in the backward linkage-based GVC participation index; (2) the ML index is greater than 1 in most years, indicating that the green upgrade of China’s manufacturing sectors shows an uptrend; (3) for both forward and backward linkage, the rise of the GVC and complex GVC participation indexes significantly promotes the green upgrade of manufacturing sectors. Finally, GVC participation of China’s manufacturing sectors promotes green upgrade mainly through green technology progress. The conclusions have empirical evidence and policy implications for the advancement to medium- and high-end GVC participation and the green transition of China’s manufacturing sectors.
How We Might Further Integrate Considerations of Environmental Impact When Assessing the Value of Health Technologies
Authors: Greenwood Dufour Barbara , Weeks Laura , De Angelis Gino , Marchand Dave K. , Kaunelis David , Severn Melissa , Walter Melissa , Mittmann Nicole
Published: September 2022

There is growing awareness of the impact health technologies can have on the environment and the negative consequences of these environmental impacts on human health. However, health system decision-makers may lack the expertise, data, or resources to incorporate environmental considerations when making decisions about the adoption and use of health technologies. In this article, we describe how health technology assessment (HTA) is evolving to address climate change by providing health system decision-makers with the information they can use to reduce the impact of health care systems on the environment. Our objective is to consider approaches for including the environment domain when conducting an HTA—in particular, the use of the deliberative process—and for determining when the domain should be included. We explore the challenges of gathering the relevant data necessary to assess the environmental impact of a health technology, and we describe a “triage” approach for determining when an in-depth environmental impact assessment is warranted. We also summarize related initiatives from HTA agencies around the world.
Spatial-Temporal Characteristics of Multi-Hazard Resilience in Ecologically Fragile Areas of Southwest China: A Case Study in Aba
Authors: Zhou Ying , Su Qihao , Li Yulian , Li Xingwei
Published: September 2022

Aba’s topography, weather, and climate make it prone to landslides, mudslides, and other natural disasters, which limit economic and social growth. Assessing and improving regional resilience is important to mitigate natural disasters and achieve sustainable development. In this paper, the entropy weight method is used to calculate the resilience of Aba under multi-hazard stress from 2010 to 2018 by combining the existing framework with the disaster resilience of the place (DROP) model. Then spatial-temporal characteristics are analyzed based on the coefficient of variation and exploratory spatial data analysis (ESDA). Finally, partial least squares (PLS) regression is used to identify the key influences on disaster resilience. The results show that (1) the disaster resilience in Aba increased from 2010 to 2018 but dropped in 2013 and 2017 due to large-scale disasters. (2) There are temporal and spatial differences in the level of development in each of the Aba counties. From 2010 to 2016, disaster resilience shows a significant positive spatial association and high-high (HH) aggregation in the east and low-low (LL) aggregation in the west. Then the spatial aggregation weakened after 2017. This paper proposes integrating regional development, strengthening the development level building, and emphasizing disaster management for Aba.
A Mobile Application to Help Self-Manage Pain Severity, Anxiety, and Depressive Symptoms in Patients with Fibromyalgia Syndrome: A Pilot Study
Authors: Miró Jordi , Lleixà-Daga Meritxell , de la Vega Rocío , Llorens-Vernet Pere , Jensen Mark P.
Published: September 2022

Treatment for individuals with fibromyalgia syndrome (FMS) is complex and is not always accessible to those who could benefit. The aim of this study was to conduct a preliminary evaluation of a mobile-app-delivered, cognitive behavioral treatment (CBT)-based intervention in helping adults self-manage fibromyalgia symptoms. A total of 100 adults with FMS (M [SD] age = 49.81, [9.99] years; 94% women) were given access to the digital treatment program and downloaded the app. Pain severity, anxiety symptoms, depression symptoms, fatigue, and sleep quality were assessed at pre-treatment, post-treatment, and 3-month follow-up. Fifty-three of the potential participants completed the 47-day treatment. Data showed significant improvements in pain severity (p = 0.007, d = 0.43), anxiety (p = 0.011, d = 0.40) and depressive symptoms (p = 0.001, d = 0.50) from pre-treatment to post-treatment. The effect sizes associated with app use are consistent with improvements seen in previously published clinical trials of CBT for FMS. Improvements were generally maintained, although there was some decrease in the outcomes from post-treatment to the 3-month follow-up. Most participants reported that they were very satisfied with the app. The use of the app was associated with similar levels of improvements found with in-person CBT treatment for FMS. Research to evaluate the effectiveness of the app in a controlled trial is warranted.
Evaluation of Trophic Structure and Energy Flow in a Pelteobagrus fulvidraco Integrated Multi-Trophic Aquaculture System
Authors: Zhao Yuxi , Liu Xingguo , Lu Ming , Zhou Runfeng , Sun Zhaoyun , Xiao Shuwen
Published: September 2022

An integrated multi-trophic aquaculture system (IMTA) combined muti-trophic organism cultivation with ecological engineering facilities effectively improves energy utilization efficiency and reduces pollution emission, which promotes the development of the aquaculture industry. In this study, an Ecopath model was used to analyze the Pelteobagrus fulvidraco-integrated multi-trophic aquaculture system (FMRP). The results showed that the effective trophic level range of FMRP was low (1~2.566), and the energy throughput was mainly concentrated in trophic level I (65.39%). The utilization rate of commercial fish feed was high. Due to the lack of predators for detritus and primary producers (Oryza sativa L. and hydrophyte), the energy throughput of detritus and the primary production were not fully utilized. The ascendency/total development capacity (A/TDC) and overhead/total development capacity (O/TDC) were 0.29 and 0.59, respectively, which indicated that the aquaculture system had high elasticity and strong anti-perturbation ability, but the stability could be substantially improved. The results of the carrying capacity assessment showed that the maximal single increments of Pelteobagrus fulvidraco fry and juvenile were 0.12 g/m2 and 0.42 g/m2, respectively, and the maximal common increments of Pelteobagrus fulvidraco fry and juvenile were 0.10 g/m2 and 0.10 g/m2, respectively, which indicated that there was insufficient space for increment. The study showed that the FMRP still needed to be improved in the aspects of polyculture species, energy consumption and stability. It would be necessary for the FMRP to perform further optimization and enhancement on the energy utilization efficiency, system stability and comprehensive benefits.
CSR in Professional Football in Times of Crisis: New Ways in a Challenging New Normal
Authors: Oeckl Severin J. S. , Morrow Stephen
Published: September 2022

While corporate social responsibility (CSR) activities are well-established among football clubs, COVID-19 challenged clubs’ capacity and commitment to continue delivering in times of crisis. Focusing on Scottish Professional Football League (SPFL) Premiership clubs and their charitable foundations, we examined challenges presented by restrictions and limited resources and how these impacted the decision making of CSR managers, as well as their prioritisation of projects undertaken. Qualitative research methods were applied in a two-step process. A content analysis drawing on publicly available resources provided a holistic overview of the CSR landscape in Scottish football. Subsequent semi-structured interviews with CSR managers of four clubs’ foundations offered detailed insights into crisis response. We found that resource limitations resulted primarily in operational rather than financial difficulties. To remain functional and consistent with their motives, foundations initiated new ways to address target groups’ social needs. Specifically, delivery shifted towards direct help and short-term support. While foundations continued to benefit from being associated with the parent football club, autonomy from the club was a critical success factor intensifying stakeholder relationships and community links. COVID-19-related disruptive factors resulted in more rapid decision making and greater empowerment of operational staff. Lessons learned have potential implications for CSR management post-pandemic.
Relations between Structure and Zn(II) Binding Affinity Shed Light on the Mechanisms of Rad50 Hook Domain Functioning and Its Phosphorylation
Authors: Tran Józef Ba , Padjasek Michał , Krężel Artur
Published: September 2022

The metal binding at protein–protein interfaces is still uncharted territory in intermolecular interactions. To date, only a few protein complexes binding Zn(II) in an intermolecular manner have been deeply investigated. The most notable example of such interfaces is located in the highly conserved Rad50 protein, part of the Mre11-Rad50-Nbs1 (MRN) complex, where Zn(II) is required for homodimerization (Zn(Rad50)2). The high stability of Zn(Rad50)2 is conserved not only for the protein derived from the thermophilic archaeon Pyrococcus furiosus (logK12 = 20.95 for 130-amino-acid-long fragment), which was the first one studied, but also for the human paralog studied here (logK12 = 19.52 for a 183-amino-acid-long fragment). As we reported previously, the extremely high stability results from the metal-coupled folding process where particular Rad50 protein fragments play a critical role. The sequence–structure–stability analysis based on human Rad50 presented here separates the individual structural components that increase the stability of the complex, pointing to amino acid residues far away from the Zn(II) binding site as being largely responsible for the complex stabilization. The influence of the individual components is very well reflected by the previously published crystal structure of the human Rad50 zinc hook (PDB: 5GOX). In addition, we hereby report the effect of phosphorylation of the zinc hook domain, which exerts a destabilizing effect on the domain. This study identifies factors governing the stability of metal-mediated protein–protein interactions and illuminates their molecular basis.
Arabidopsis Ubiquitin-Conjugating Enzymes UBC4, UBC5, and UBC6 Have Major Functions in Sugar Metabolism and Leaf Senescence
Authors: Wang Sheng , Cao Ling , Willick Ian R. , Wang Hong , Tanino Karen K.
Published: September 2022

The ubiquitin-conjugating enzyme (E2) is required for protein ubiquitination. Arabidopsis has 37 E2s grouped into 14 subfamilies and the functions for many of them are unknown. We utilized genetic and biochemical methods to study the roles of Arabidopsis UBC4, UBC5, and UBC6 of the E2 subfamily IV. The Arabidopsis ubc4/5/6 triple mutant plants had higher levels of glucose, sucrose, and starch than the control plants, as well as a higher protein level of a key gluconeogenic enzyme, cytosolic fructose 1,6-bisphosphatase 1 (cyFBP). In an in vitro assay, the proteasome inhibitor MG132 inhibited the degradation of recombinant cyFBP whereas ATP promoted cyFBP degradation. In the quadruple mutant ubc4/5/6 cyfbp, the sugar levels returned to normal, suggesting that the increased sugar levels in the ubc4/5/6 mutant were due to an increased cyFBPase level. In addition, the ubc4/5/6 mutant plants showed early leaf senescence at late stages of plant development as well as accelerated leaf senescence using detached leaves. Further, the leaf senescence phenotype remained in the quadruple ubc4/5/6 cyfbp mutant. Our results suggest that UBC4/5/6 have two lines of important functions, in sugar metabolism through regulating the cyFBP protein level and in leaf senescence likely through a cyFBP-independent mechanism.
Waldenström Macroglobulinemia: Mechanisms of Disease Progression and Current Therapies
Authors: Boutilier Ava J. , Huang Lina , Elsawa Sherine F.
Published: September 2022

Waldenström macroglobulinemia is an indolent, B-cell lymphoma without a known cure. The bone marrow microenvironment and cytokines both play key roles in Waldenström macroglobulinemia (WM) tumor progression. Only one FDA-approved drug exists for the treatment of WM, Ibrutinib, but treatment plans involve a variety of drugs and inhibitors. This review explores avenues of tumor progression and targeted drug therapy that have been investigated in WM and related B-cell lymphomas.
Lipopolysaccharides and Cellular Senescence: Involvement in Atherosclerosis
Authors: Suzuki Kaori , Susaki Etsuo A. , Nagaoka Isao
Published: September 2022

Atherosclerosis is a chronic inflammatory disease of the vascular walls related to aging. Thus far, the roles of cellular senescence and bacterial infection in the pathogenesis of atherosclerosis have been speculated to be independent of each other. Some types of macrophages, vascular endothelial cells, and vascular smooth muscle cells are in a senescent state at the sites of atherosclerotic lesions. Likewise, bacterial infections and accumulations of lipopolysaccharide (LPS), an outer-membrane component of Gram-negative bacteria, have also been observed in the atherosclerotic lesions of patients. This review introduces the integration of these two potential pathways in atherosclerosis. Previous studies have suggested that LPS directly induces cellular senescence in cultured monocytes/macrophages and vascular cells. In addition, LPS enhances the inflammatory properties (senescence-associated secretory phenotype [SASP]) of senescent endothelial cells. Thus, LPS derived from Gram-negative bacteria could exaggerate the pathogenesis of atherosclerosis by inducing and enhancing cellular senescence and the SASP-associated inflammatory properties of specific vascular cells in atherosclerotic lesions. This proposed mechanism can provide novel approaches to preventing and treating this common age-related disease.
Dexamethasone-Loaded Hydrogels Improve Motor and Cognitive Functions in a Rat Mild Traumatic Brain Injury Model
Authors: Macks Christian , Jeong Daun , Bae Sooneon , Webb Ken , Lee Jeoung Soo
Published: September 2022

Functional recovery following traumatic brain injury (TBI) is limited due to progressive neuronal damage resulting from secondary injury-associated neuroinflammation. Steroidal anti-inflammatory drugs, such as dexamethasone (DX), can reduce neuroinflammation by activated microglia and infiltrated macrophages. In our previous work, we developed hydrolytically degradable poly(ethylene) glycol-bis-(acryloyloxy acetate) (PEG-bis-AA) hydrogels with dexamethasone (DX)-conjugated hyaluronic acid (HA-DXM) and demonstrated that dexamethasone-loaded hydrogels (PEG-bis-AA/HA-DXM) can reduce neuroinflammation, apoptosis, and lesion volume and improve neuronal cell survival and motor function recovery at seven days post-injury (DPI) in a rat mild-TBI model. In this study, we investigate the effects of the local application of PEG-bis-AA/HA-DXM hydrogels on motor function recovery at 7 DPI and cognitive functional recovery as well as secondary injury at 14 DPI in a rat mild-CCI TBI model. We observed that PEG-bis-AA/HA-DXM-treated animals exhibit significantly improved motor functions by the rotarod test and cognitive functions by the Morris water maze test compared to untreated TBI animals. We also observed that PEG-bis-AA/HA-DXM hydrogels reduce the inflammatory response, apoptosis, and lesion volume compared to untreated animals at 14 DPI. Therefore, PEG-bis-AA/HA-DXM hydrogels can be promising a therapeutic intervention for TBI treatment.
Preparation and Characterization of Degradable Cellulose−Based Paper with Superhydrophobic, Antibacterial, and Barrier Properties for Food Packaging
Authors: Jiang Xiaofan , Li Qiang , Li Xinting , Meng Yao , Ling Zhe , Ji Zhe , Chen Fushan
Published: September 2022

A great paradigm for foremost food packaging is to use renewable and biodegradable lignocellulose−based materials instead of plastic. Novel packages were successfully prepared from the cellulose paper by coating a mixture of polylactic acid (PLA) with cinnamaldehyde (CIN) as a barrier screen and nano silica−modified stearic acid (SA/SiO2) as a superhydrophobic layer. As comprehensively investigated by various tests, results showed that the as−prepared packages possessed excellent thermal stability attributed to inorganic SiO2 incorporation. The excellent film−forming characteristics of PLA improved the tensile strength of the manufactured papers (104.3 MPa) as compared to the original cellulose papers (70.50 MPa), enhanced by 47.94%. Benefiting from the rough nanostructure which was surface−modified by low surface energy SA, the contact angle of the composite papers attained 156.3°, owning superhydrophobic performance for various liquids. Moreover, the composite papers showed excellent gas, moisture, and oil bacteria barrier property as a result of the reinforcement by the functional coatings. The Cobb300s and WVP of the composite papers were reduced by 100% and 88.56%, respectively, and their antibacterial efficiency was about 100%. As the novel composite papers have remarkable thermal stability, tensile strength, and barrier property, they can be exploited as a potential candidate for eco−friendly, renewable, and biodegradable cellulose paper−based composites for the substitute of petroleum−derived packages.
Formulation, Characterisation and Evaluation of the Antihypertensive Peptides, Isoleucine-Proline-Proline and Leucine-Lysine-Proline in Chitosan Nanoparticles Coated with Zein for Oral Drug Delivery
Authors: Khalid Danish Minna , Gleeson John P. , Brayden David J. , Byrne Hugh J. , Frías Jesus M. , Ryan Sinéad M.
Published: September 2022

Isoleucine-Proline-Proline (IPP) and Leucine-Lysine-Proline (LKP) are food-derived tripeptides whose antihypertensive functions have been demonstrated in hypertensive rat models. However, peptides display low oral bioavailability due to poor intestinal epithelial permeability and instability. IPP and LKP were formulated into nanoparticles (NP) using chitosan (CL113) via ionotropic gelation and then coated with zein. Following addition of zein, a high encapsulation efficiency (EE) (>80%) was obtained for the NP. In simulated gastric fluid (SGF), 20% cumulative release of the peptides was achieved after 2 h, whereas in simulated intestinal fluid (SIF), ~90% cumulative release was observed after 6 h. Higher colloidal stability (39–41 mV) was observed for the coated NP compared to uncoated ones (30–35 mV). In vitro cytotoxicity studies showed no reduction in cellular viability of human intestinal epithelial Caco-2 and HepG2 liver cells upon exposure to NP and NP components. Administration of NP encapsulating IPP and LKP by oral gavage to spontaneously hypertensive rats (SHR) attenuated systolic blood pressure (SBP) for 8 h. This suggests that the NP provide appropriate release to achieve prolonged hypotensive effects in vivo. In conclusion, chitosan-zein nanoparticles (CZ NP) have potential as oral delivery system for the encapsulation of IPP and LKP.
Temperature-Biased miRNA Expression Patterns during European Sea Bass (Dicentrarchus labrax) Development
Authors: Papadaki Maria , Kaitetzidou Elisavet , Papadakis Ioannis E. , Sfakianakis Dimitris G. , Papandroulakis Nikos , Mylonas Constantinos C. , Sarropoulou Elena
Published: September 2022

Environmental effects and, particularly, temperature changes have been demonstrated to influence the activity, function, and well-being of teleosts. Temperature may change seasonally in the wild, and in captivity under aquaculture operations. Moreover, climate change is expected to shift temperature profiles worldwide. MicroRNAs (miRNA) are important temperature-sensitive gene-expression regulators acting at the post-transcriptional level. They are known to be key regulators in development, reproduction, and immune responses. Therefore, early larval development of the European sea bass (Dicentrarchus labrax), one of the most extensively cultured species in Mediterranean aquaculture, was investigated at early rearing temperatures, i.e., 15, 17.5, and 20 °C, in regard to the impact of temperatures on miRNAs through sncRNA high-throughput sequencing but also at the phenotypic level in terms of growth, sex, vision, and skeletal deformities. Expression profiling revealed stage- and temperature-specific miRNA expression targeting genes with roles in reproduction and immune response mainly at the flexion and all-fins stages. Similar stage- and temperature-specific results were also observed concerning the number of rod cells and lower jaw elongation. The present work presents for the first time highly promising results on the influence of early rearing temperature at the post-transcriptional level during European sea bass development, with a putative impact on reproduction and immune response, as well as regarding teleost vision and larval development.
The Utilization of Physiologically Active Molecular Components of Grape Seeds and Grape Marc
Authors: Hegedüs Imre , Andreidesz Kitti , Szentpéteri József L. , Kaleta Zoltán , Szabó László , Szigeti Krisztián , Gulyás Balázs , Padmanabhan Parasuraman , Budan Ferenc , Máthé Domokos
Published: September 2022

Nutritional interventions may highly contribute to the maintenance or restoration of human health. Grapes (Vitis vinifera) are one of the oldest known beneficial nutritional components of the human diet. Their high polyphenol content has been proven to enhance human health beyond doubt in statistics-based public health studies, especially in the prevention of cardiovascular disease and cancer. The current review concentrates on presenting and classifying polyphenol bioactive molecules (resveratrol, quercetin, catechin/epicatechin, etc.) available in high quantities in Vitis vinifera grapes or their byproducts. The molecular pathways and cellular signaling cascades involved in the effects of these polyphenol molecules are also presented in this review, which summarizes currently available in vitro and in vivo experimental literature data on their biological activities mostly in easily accessible tabular form. New molecules for different therapeutic purposes can also be synthesized based on existing polyphenol compound classes available in high quantities in grape, wine, and grape marc. Therefore an overview of these molecular structures is provided. Novel possibilities as dendrimer nanobioconjugates are reviewed, too. Currently available in vitro and in vivo experimental literature data on polyphenol biological activities are presented in easily accessible tabular form. The scope of the review details the antidiabetic, anticarcinogenic, antiviral, vasoprotective, and neuroprotective roles of grape-origin flavonoids. The novelty of the study lies in the description of the processing of agricultural by-products (grape seeds and skins) of industrial relevance, and the detailed description of the molecular mechanisms of action. In addition, the review of the clinical therapeutic applications of polyphenols is unique as no summary study has yet been done.
Taking a Breather: Advances in Interleukin 5 Inhibition for Asthma Relief
Authors: Massey Oliver William , Suphioglu Cenk
Published: September 2022

Interleukin 5 (IL-5) is a major cytokine responsible for eosinophil proliferation, migration and degranulation. Eosinophils play a considerable role in the manifestation of type 2 asthma, and therefore this makes IL-5 a unique and clinically important target for therapeutic intervention. Due to the critical role that IL-5 plays in all areas of eosinophil activity, it has been identified and targeted by three therapeutics, Mepolizumab, Benralizumab and Reslizumab. This review describes the IL-5 pathway and presents the clinical trial history of the three IL-5 inhibitors, to provide insight into the role of IL-5 in clinical asthma presentation. Additionally, this review aims to foster further investigation into the IL-5 pathway by describing current novel therapeutic discovery strategies with monoclonal antibodies.
Strategies to Convert Cells into Hyaline Cartilage: Magic Spells for Adult Stem Cells
Authors: Kurenkova Anastasiia D. , Romanova Irina A. , Kibirskiy Pavel D. , Timashev Peter , Medvedeva Ekaterina V.
Published: September 2022

Damaged hyaline cartilage gradually decreases joint function and growing pain significantly reduces the quality of a patient’s life. The clinically approved procedure of autologous chondrocyte implantation (ACI) for treating knee cartilage lesions has several limits, including the absence of healthy articular cartilage tissues for cell isolation and difficulties related to the chondrocyte expansion in vitro. Today, various ACI modifications are being developed using autologous chondrocytes from alternative sources, such as the auricles, nose and ribs. Adult stem cells from different tissues are also of great interest due to their less traumatic material extraction and their innate abilities of active proliferation and chondrogenic differentiation. According to the different adult stem cell types and their origin, various strategies have been proposed for stem cell expansion and initiation of their chondrogenic differentiation. The current review presents the diversity in developing applied techniques based on autologous adult stem cell differentiation to hyaline cartilage tissue and targeted to articular cartilage damage therapy.
Anti-TNF Therapies Suppress Adipose Tissue Inflammation in Crohn’s Disease
Authors: Boronat-Toscano Albert , Monfort-Ferré Diandra , Menacho Margarita , Caro Aleidis , Bosch Ramon , Espina Beatriz , Algaba-Chueca Francisco , Saera-Vila Alfonso , Moliné Alicia , Marti Marc , Espin Eloy , Millan Mónica , Serena Carolina
Published: September 2022

Anti-TNF biologics have been shown to markedly improve the quality of life for patients with Crohn’s disease (CD), yet one-third of patients fail to benefit from this treatment. Patients with CD develop a characteristic wrapping of visceral adipose tissue (VAT) in the inflamed intestinal area, termed creeping fat, and it is known that adipose tissue expansion influences the efficacy of anti-TNF drugs. We questioned whether anti-TNF therapies impact the creeping fat in CD, which might affect the outcome of the disease. Adipose tissue biopsies were obtained from a cohort of 14 patients with CD that received anti-TNF drugs and from 29 non-anti-TNF-treated patients (control group) matched by sex, age, and body mass index undergoing surgical interventions for symptomatic complications. We found that anti-TNF therapies restored adipose tissue morphology and suppressed immune cell infiltration in the creeping fat. Additionally, anti-TNF treatments appeared to markedly improve the pro-inflammatory phenotype of adipose-tissue macrophages and adipose-tissue-derived stem cells. Our study provides evidence that anti-TNF medications influence immune cells and progenitor cells in the creeping of patients with CD, suppressing inflammation. We propose that perilesional VAT should be considered when administering anti-TNF therapy in patients with CD.
Urine NMR Metabolomics for Precision Oncology in Colorectal Cancer
Authors: Brezmes Jesús , Llambrich Maria , Cumeras Raquel , Gumà Josep
Published: September 2022

Metabolomics is a fundamental approach to discovering novel biomarkers and their potential use for precision medicine. When applied for population screening, NMR-based metabolomics can become a powerful clinical tool in precision oncology. Urine tests can be more widely accepted due to their intrinsic non-invasiveness. Our review provides the first exhaustive evaluation of NMR metabolomics for the determination of colorectal cancer (CRC) in urine. A specific search in PubMed, Web of Science, and Scopus was performed, and 10 studies met the required criteria. There were no restrictions on the query for study type, leading to not only colorectal cancer samples versus control comparisons, but also prospective studies of surgical effects. With this review, all compounds in the included studies were merged into a database. In doing so, we identified up to 100 compounds in urine samples, and 11 were found in at least three articles. Results were analyzed in three groups: case (CRC and adenomas)/control, pre-/post-surgery, and combining both groups. When combining the case-control and the pre-/post-surgery groups, up to twelve compounds were found to be relevant. Seven down-regulated metabolites in CRC were identified, creatinine, 4-hydroxybenzoic acid, acetone, carnitine, d-glucose, hippuric acid, l-lysine, l-threonine, and pyruvic acid, and three up-regulated compounds in CRC were identified, acetic acid, phenylacetylglutamine, and urea. The pathways and enrichment analysis returned only two pathways significantly expressed: the pyruvate metabolism and the glycolysis/gluconeogenesis pathway. In both cases, only the pyruvic acid (down-regulated in urine of CRC patients, with cancer cell proliferation effect in the tissue) and acetic acid (up-regulated in urine of CRC patients, with chemoprotective effect) were present.
Synthesis, Anticancer Activity and Molecular Docking Studies of Novel N-Mannich Bases of 1,3,4-Oxadiazole Based on 4,6-Dimethylpyridine Scaffold
Authors: Strzelecka Małgorzata , Glomb Teresa , Drąg-Zalesińska Małgorzata , Kulbacka Julita , Szewczyk Anna , Saczko Jolanta , Kasperkiewicz-Wasilewska Paulina , Rembiałkowska Nina , Wojtkowiak Kamil , Jezierska Aneta , Świątek Piotr
Published: September 2022

Cancer is one of the greatest challenges in modern medicine today. Difficult and long-term treatment, the many side effects of the drugs used and the growing resistance to treatment of neoplastic cells necessitate new approaches to therapy. A very promising targeted therapy is based on direct impact only on cancer cells. As a continuation of our research on new biologically active molecules, we report herein the design, synthesis and anticancer evaluation of a new series of N-Mannich-base-type hybrid compounds containing morfoline or different substituted piperazines moieties, a 1,3,4-oxadiazole ring and a 4,6-dimethylpyridine core. All compounds were tested for their potential cytotoxicity against five human cancer cell lines, A375, C32, SNB-19, MCF-7/WT and MCF-7/DX. Two of the active N-Mannich bases (compounds 5 and 6) were further evaluated for growth inhibition effects in melanoma (A375 and C32), and normal (HaCaT) cell lines using clonogenic assay and a population doubling time test. The apoptosis was determined with the neutral version of comet assay. The confocal microscopy method enabled the visualization of F-actin reorganization. The obtained results demonstrated that compounds 5 and 6 have cytotoxic and proapoptotic effects on melanoma cells and are capable of inducing F-actin depolarization in a dose-dependent manner. Moreover, computational chemistry approaches, molecular docking and electrostatic potential were employed to study non-covalent interactions of the investigated compounds with four receptors. It was found that all the examined molecules exhibit a similar binding affinity with respect to the chosen reference drugs.
Emerging Roles of Ceramides in Breast Cancer Biology and Therapy
Authors: Pal Purab , Atilla-Gokcumen G. Ekin , Frasor Jonna
Published: September 2022

One of the classic hallmarks of cancer is the imbalance between elevated cell proliferation and reduced cell death. Ceramide, a bioactive sphingolipid that can regulate this balance, has long been implicated in cancer. While the effects of ceramide on cell death and therapeutic efficacy are well established, emerging evidence indicates that ceramide turnover to downstream sphingolipids, such as sphingomyelin, hexosylceramides, sphingosine-1-phosphate, and ceramide-1-phosphate, is equally important in driving pro-tumorigenic phenotypes, such as proliferation, survival, migration, stemness, and therapy resistance. The complex and dynamic sphingolipid network has been extensively studied in several cancers, including breast cancer, to find key sphingolipidomic alterations that can be exploited to develop new therapeutic strategies to improve patient outcomes. Here, we review how the current literature shapes our understanding of how ceramide synthesis and turnover are altered in breast cancer and how these changes offer potential strategies to improve breast cancer therapy.
Sensorineural Hearing Loss in Sjögren’s Syndrome
Authors: Okawa Yuko , Ihara Kenji
Published: September 2022

Sjögren’s syndrome is a chronic autoimmune disease characterized by systemic dysfunction of exocrine glands, mainly the salivary and lachrymal glands. Sjögren’s syndrome consists of two forms: primary Sjögren’s syndrome, which is characterized by dry eyes and dry mouth without autoimmune diseases; and secondary Sjögren’s syndrome, which is characterized by symptoms associated with other autoimmune diseases, such as systemic lupus erythematosus. Disease severities vary considerably from mild glandular dryness to severe glandular involvement with numerous extraglandular and systemic features. Sensorineural hearing loss is sometimes observed in both primary and secondary Sjögren’s syndrome. This review article consists of (1) Pathology of Sjögren’s syndrome, (2) Clinical manifestation of Sjögren’s syndrome, (3) Autoimmune inner ear disease, (4) Histoanatomical features of the inner ear, (5) Immunological characteristics of the inner ear, (6) Pathophysiology of autoimmune inner ear disease, (7) Treatment for sensorineural hearing loss in Sjögren’s syndrome, and (8) Future direction. Finally, we introduce a recently developed disease model of salivary gland inflammation and discuss future expectations for the treatment of sensorineural hearing loss in Sjögren’s syndrome.