bluuebunny/crossref_metadata_2025 huggingface dataset:
Coffee Silver Skin—Health Safety, Nutritional Value, and Microwave Extraction of Proteins
Authors: Biondić Fučkar Vedran , Božić Angela , Jukić Anita , Krivohlavek Adela , Jurak Gordana , Tot Ana , Serdar Sonja , Žuntar Irena , Režek Jambrak Anet
Published: January 2023

The aim of this research was to evaluate the health safety (concentrations of pesticide residues and heavy metals) and nutritional parameters (macro- and microminerals and crude fibre) of coffee silver skin (CS), as well to isolate proteins from this by-product using an optimised microwave extraction method. The CS by-product samples showed the highest amount of potassium, followed by calcium, magnesium, and sodium. Iron was found in the highest quantity among the microminerals, followed by copper, manganese, zinc, and chromium. The CS sample showed a large amount of fibre and a moderate quantity of proteins obtained by the optimised microwave extraction method. Four heavy metals (nickel, lead, arsenic, and cadmium) were detected, and all were under the permitted levels. Among the 265 analysed pesticides, only three showed small quantity. The results for the proteins extracted by microwave showed that the total protein concentration values ranged from 0.52 ± 0.01 mg/L to 0.77 ± 0.07 mg/L. The highest value of the concentration of total proteins (0.77 ± 0.07 mg/L) was found in the sample treated for 9 min, using a power of 200 W. Based on these results, it can be concluded that CS is a healthy and nutritionally rich nutraceutical that could be used in the production of new products in the food industry and other industries.
Acknowledgment to the Reviewers of Games in 2022
Authors:   Games Editorial Office
Published: January 2023

High-quality academic publishing is built on a rigorous peer review process, and Games is no exception, upholding its high standards for published papers due to the outstanding efforts of our reviewers [...]
Polypyrrole-Barium Ferrite Magnetic Cryogels for Water Purification
Authors: Milakin Konstantin A. , Taboubi Oumayma , Acharya Udit , Lhotka Miloslav , Pokorný Václav , Konefał Magdalena , Kočková Olga , Hromádková Jiřina , Hodan Jiří , Bober Patrycja
Published: January 2023

Magnetic polypyrrole-gelatin-barium ferrite (PPy-G-BaFe) cryogels/aerogels were synthesized by one-step oxidative cryopolymerization of pyrrole in the presence of various fractions of barium ferrite (BaFe) nanoparticles, dispersed in aqueous gelatin solution. The successful incorporation of BaFe into the composites was confirmed by elemental analysis and scanning electron microscopy paired with an energy-dispersive X-ray detector. The maximum achieved content of BaFe in the resulting material was 3.9 wt%. The aerogels with incorporated BaFe had significantly higher specific surface area and conductivity, reaching 19.3 m2 g−1 and 4 × 10−4 S cm−1, respectively, compared to PPy-G aerogel, prepared in the absence of BaFe (7.3 m2 g−1 and 1 × 10−5 S cm−1). The model adsorption experiment using an anionic dye, Reactive Black 5, showed that magnetic PPy-G-BaFe aerogel, prepared at 10 wt% BaFe fraction, had significantly higher adsorption rate and higher adsorption capacity, compared to PPy-G (dye removal fraction 99.6% and 89.1%, respectively, after 23 h). Therefore, the prepared PPy-G-BaFe aerogels are attractive adsorbents for water purification due to their enhanced adsorption performance and the possibility of facilitated separation from solution by a magnetic field.
Metformin Therapy and Breast Cancer Incidence in the Ha’il Region
Authors: Osman Mhdia , Muqbel Taif , Abduallh Ahad , Alanazi Shuruq , Khalifa Nasrin E. , Khojali Weam M. A. , Elagib Halima Mustafa , Hussein Weiam , Abdallah Marwa H.
Published: January 2023

Background: Metformin is a drug used to treat patients with type 2 diabetes, especially those who suffer from obesity. It is also used in the treatment of women with polycystic ovary syndrome (PCOS). This disease is related to insulin resistance and multiplied blood sugar ranges. Furthermore, it has been established that the use of metformin improves the menstrual cycles and ovulation rates of these women. Methods: A structured questionnaire was conducted to determine the prevalence of breast cancer among women using metformin in the Ha’il region. Result: The incidence of breast cancer among women using metformin in the Ha’il region is very low. Thus, it can be said that breast cancer cases declined among diabetics taking metformin. This means that metformin use is associated with a lower risk of breast cancer in women with type 2 diabetes, even in cases where these women have a family history of breast cancer. Conclusions: According to previous findings, metformin has been linked to lower breast cancer risk in women with type 2 diabetes. Furthermore, the findings of this study corroborate the literature on this subject by indicating that there is a substantial connection between metformin use and a lower risk of breast cancer in women with type 2 diabetes. However, further in vitro and in vivo experiments are crucial to investigate the protective effect of metformin against breast cancer and to confirm our findings.
Best-Worst Scaling Survey of Inpatients’ Preferences in Medical Decision-Making Participation in China
Authors: Sun Tao , Chen Hanlin , Gao Yuan , Xiang Yingru , Wang Feng , Ni Ziling , Wang Xiaohe , Huang Xianhong
Published: January 2023

This study assesses inpatients’ preferences for participating in medical decision-making and determines the factors’ rankings in order of importance and whether they vary for respondents with different characteristics. Case 1 best-worst scaling (BWS) was used for the study design. Thirteen attributes influencing inpatient medical decision-making participation were identified based on a literature review and interview results. A balanced incomplete block design was used to form choice sets for the BWS questionnaire for a cross-sectional study examining inpatients’ preferences for participating in medical decision-making. Based on results from 814 inpatient participants, the three most important factors influencing inpatients’ medical decision-making participation were inpatients’ trust in physicians, physicians’ professional expertise, and physicians’ attitudes. The mixed logit model results reflect the significant heterogeneity in respondents’ preferences for shared decision-making. To facilitate resource allocation, improve the physician-patient relationship, and encourage patient decision-making participation more actively and effectively, decision-makers should emphasize patients’ trust, enhance physicians’ ability to diagnose and treat diseases, and improve their attitudes toward providing care and communication from the perspectives of patients, physicians, and the social environment. Further research is needed on the heterogeneity of patients’ preferences for participating in medical decision-making and how to improve patient participation.
Evaluating Efficacy of a COVID-19 Alternative Care Site Preparedness Assessment Tool for Catastrophic Healthcare Surge Capacity during Pandemic Response
Authors: Scanlon Molly , Taylor Ellen , Waltz Kirsten
Published: January 2023

During the COVID-19 pandemic, implementing catastrophic healthcare surge capacity required a network of facility infrastructure beyond the immediate hospital to triage the rapidly growing numbers of infected individuals and treat emerging disease cases. Providing regional continuity-of-care requires an assessment of buildings for alternative care sites (ACS) to extend healthcare operations into non-healthcare settings. The American Institute of Architects (AIA) appointed a COVID-19 ACS Task Force involving architects, engineers, public health, and healthcare professionals to conduct a charrette (i.e., intensive workshop) to establish guidance during the alert phase of the pandemic. The task force developed an ACS Preparedness Assessment Tool (PAT) for healthcare teams to assist with their rapid evaluation of building sites for establishing healthcare operations in non-healthcare settings. The tool was quickly updated (V2.0) and then translated into multiple languages. Subsequently, the authors of this manuscript reviewed the efficacy of the PAT V2.0 in the context of reported case studies from healthcare teams who developed a COVID-19 ACS in community settings. In summary, policy makers should re-examine the role of the built environment during emergency pandemic response and its impact on patients and health professionals. An updated ACS PAT tool should be established as part of the public health preparedness for implementing catastrophic healthcare surge capacity.
Assessing the Potential of Combined SMAP and In-Situ Soil Moisture for Improving Streamflow Forecast
Authors: Wakigari Shimelis Asfaw , Leconte Robert
Published: January 2023

Soil moisture is an essential hydrological variable for a suite of hydrological applications. Its spatio-temporal variability can be estimated using satellite remote sensing (e.g., SMOS and SMAP) and in-situ measurements. However, both have their own strengths and limitations. For example, remote sensing has the strength of maintaining the spatial variability of near-surface soil moisture, while in-situ measurements are accurate and preserve the dynamics range of soil moisture at both surface and larger depths. Hence, this study is aimed at (1) merging the strength of SMAP with in-situ measurements and (2) exploring the effectiveness of merged SMAP/in-situ soil moisture in improving ensemble streamflow forecasts. The conditional merging technique was adopted to merge the SMAP-enhanced soil moisture (9 km) and its downscaled version (1 km) separately with the in-situ soil moisture collected over the au Saumon watershed, a 1025 km2 watershed located in Eastern Canada. The random forest machine learning technique was used for downscaling of the near-surface SMAP-enhanced soil moisture to 1 km resolution, whereas the exponential filter was used for vertical extrapolation of the SMAP near-surface soil moisture. A simple data assimilation technique known as direct insertion was used to update the topsoil layer of a physically-based distributed hydrological model with four soil moisture products: (1) the merged SMAP/in-situ soil moisture at 9 and 1 km resolutions; (2) the original SMAP-enhanced (9 km), (3) downscaled SMAP-enhanced (1 km), and (4) interpolated in-situ surface soil moisture. In addition, the vertically extrapolated merged SMAP/in-situ soil moisture and subsurface (rootzone) in-situ soil moisture were used to update the intermediate layer of the model. Results indicate that downscaling of the SMAP-enhanced soil moisture to 1 km resolution improved the spatial variability of soil moisture while maintaining the spatial pattern of its original counterpart. Similarly, merging of the SMAP with in- situ soil moisture preserved the dynamic range of in-situ soil moisture and maintained the spatial heterogeneity of SMAP soil moisture. Updating of the top layer of the model with the 1 km merged SMAP/in-situ soil moisture improved the ensemble streamflow forecast compared to the model updated with either the SMAP-enhanced or in-situ soil moisture alone. On the other hand, updating the top and intermediate layers of the model with surface and vertically extrapolated SMAP/in-situ soil moisture, respectively, did not further improve the accuracy of the ensemble streamflow forecast. Overall, this study demonstrated the potential of merging the SMAP and in-situ soil moisture for streamflow forecast.
A Study on the Soundscape of Underground Commercial Space in Lu’an City and Hefei City, China
Authors: Wang Su , He Huaidong , Li Fulong , Xiao Qingqing
Published: January 2023

Soundscape is an important part and one of the main factors of the underground space environment. Field surveys were conducted to evaluate the soundscape of underground commercial spaces and to compare it with the soundscape of the above-ground commercial spaces between two cities (Lu’an City and Hefei City) in China, consequently presenting the construction strategy of the soundscape of underground commercial spaces in urban areas. The results showed that the sound in the shopping center, which people found comfortable, was at the lower to intermediate level. The main sounds that people perceived as “general” sounds were environmental sounds such as music, the humming of the air conditioning, people talking, walking, and the hawking of the stores. Nevertheless, “very comfortable” sounds were background music and the sound of live performances, which were indicated in the majority of people’s opinions on evaluating a comfortable feeling, thus reflecting the impact of the sound of mall music on people’s cognitive psychology. Therefore, it is necessary to control the volume of environmental noise at a certain level so that people’s health is not adversely affected. It also helps shoppers to feel more comfortable psychologically and physiologically.
Excessive Facial Wrinkling Is Associated with COPD Occurrence—Does COPD Damage Skin Beauty and Quality?
Authors: Szczegielniak Jan , Bogacz Katarzyna , Łuniewski Jacek , Krajczy Marcin , Pilis Wiesław , Majorczyk Edyta
Published: January 2023

The aim of this study was to investigate facial wrinkling in COPD patients, its relationship with lung function parameters, and the differences in wrinkling between COPD patients and smokers without COPD. The study included 56 patients with COPD with smoking history and 84 controls. Wrinkle intensity was measured and classified using Daniell’s grading system, and the total length of wrinkles was also estimated. The predominant grades of Daniell’s scale were IV–V for COPD patients (89.3% of current and 75.0% of former smokers), III–V for controls who currently smoke (89.2%), and II–III for former (92.9%) and never smokers (100%) controls. These distributions were statistically significantly different, but current and former smokers with COPD and COPD former smokers and control current smokers did not differ. In terms of the total length of wrinkles, the COPD patients possessed significantly longer wrinkles than the control subgroups (all p-values were <0.004). Negative correlations between wrinkle length and lung parameters were found. This phenomenon seems to be independent of smoking, but the length of wrinkles is related to lung function parameters. It seems that not only smoking but also COPD damages skin beauty and quality.
A Effectiveness-and Efficiency-Based Improved Approach for Measuring Ecological Well-Being Performance in China
Authors: He Bei , Du Xiaoyun , Li Junkang , Chen Dan
Published: January 2023

Finding solutions to the challenges posed by China’s urbanization is an urgent, pressing global concern. An effective approach for evaluating the ecological well-being performance (EWP) is a guideline for improvement. Most previous studies have focused on the evaluation of EWP efficiency without considering the effectiveness of the EWP, which may mislead the practice of improving the EWP. This paper proposed a bi-dimensional effectiveness and efficiency perspective evaluation of the EWP for pursuing sustainable development goals. The Ecological Consumption Index and the Human Development Index are selected to evaluate indicators for the EWP. The entropy method, line-weighted method, and four-quadrant evaluation framework are used to disclose EWP effectiveness. A Super SBM model and the DEA moving split-windows analysis method are applied to calculate the EWP efficiency. Data from 30 provinces in China for the period of 1997 to 2019 have been collected for empirical study to demonstrate the effectiveness of the proposed method. The main findings of the case study are: (1) The ECI and HDI increased during the study period, while the annual average value of the EWP efficiency among 30 provinces in China has decreased with fluctuation; (2) provinces in southern China and Chongqing have a low level of ECI and demonstrate good performance in the HDI; and (3) most developed regions, such as Beijing, Shanghai, and Guangdong, have not presented the best EWPs. The results of this study can provide a basis for understanding the EWP in China so as to formulate targeted sustainable-development strategies.
Effects of Different Hamstring Eccentric Exercise Programs on Preventing Lower Extremity Injuries: A Systematic Review and Meta-Analysis
Authors: Hu Chenxi , Du Zhikun , Tao Mei , Song Yafeng
Published: January 2023

This systematic review and meta-analysis aims to investigate the effects and differences of various hamstring eccentric training protocols for the prevention of lower limb injuries, and we further propose a more refined hamstring eccentric training protocol for the prevention of lower limb injuries. A literature search for the effects of hamstring eccentric training on lower extremity sports injuries was conducted using the PubMed, Web of Science, and EMBASE databases, and the literature was searched covering the period from the date of the database’s creation to 20 August 2022. A meta-analysis of the included literature was performed using R.4.21 for lower extremity injuries, injuries in various parts of the lower extremity, and subgroup analysis for exercise frequency, exercise cycle, and exercise population. A total of 23 randomized controlled trial (RCT) studies were found to be included in the meta-analysis, and 15 of these trials, totaling 14,721 patients, were determined to be included in the overall lower extremity injury prevention effect. The analysis showed that the implementation of a hamstring eccentric training program reduced lower extremity injuries by 28%, and it resulted in a 46% decrease in hamstring injury rate and a 34% decrease in knee injury rate. The subgroup analysis revealed that the frequency of exercise was most significant in the twice-a-week exercise group, that the exercise program was most effective in preventing injuries in the 21–30-week exercise period, and that the program was most effective in preventing injuries in elite athletes and amateur adult athletic populations, compared with adolescents.
Metallic Nanosystems in the Development of Antimicrobial Strategies with High Antimicrobial Activity and High Biocompatibility
Authors: Skłodowski Karol , Chmielewska-Deptuła Sylwia Joanna , Piktel Ewelina , Wolak Przemysław , Wollny Tomasz , Bucki Robert
Published: January 2023

Antimicrobial resistance is a major and growing global problem and new approaches to combat infections caused by antibiotic resistant bacterial strains are needed. In recent years, increasing attention has been paid to nanomedicine, which has great potential in the development of controlled systems for delivering drugs to specific sites and targeting specific cells, such as pathogenic microbes. There is continued interest in metallic nanoparticles and nanosystems based on metallic nanoparticles containing antimicrobial agents attached to their surface (core shell nanosystems), which offer unique properties, such as the ability to overcome microbial resistance, enhancing antimicrobial activity against both planktonic and biofilm embedded microorganisms, reducing cell toxicity and the possibility of reducing the dosage of antimicrobials. The current review presents the synergistic interactions within metallic nanoparticles by functionalizing their surface with appropriate agents, defining the core structure of metallic nanoparticles and their use in combination therapy to fight infections. Various approaches to modulate the biocompatibility of metallic nanoparticles to control their toxicity in future medical applications are also discussed, as well as their ability to induce resistance and their effects on the host microbiome.
Carbonyl Cyanide 3-Chloro Phenyl Hydrazone (CCCP) Restores the Colistin Sensitivity in Brucella intermedia
Authors: Zoaiter Malak , Zeaiter Zaher , Mediannikov Oleg , Sokhna Cheikh , Fournier Pierre-Edouard
Published: January 2023

Brucella intermedia (formerly Ochrobactrum intermedium), a non-fermentative bacterium, has been isolated from animals and human clinical specimens. It is naturally resistant to polymyxins, including colistin (CO), and may cause opportunistic infections in humans. We isolated six Brucella intermedia strains from Senegalese monkey stool. In order to determine whether an efflux pump mechanism was involved in CO resistance in B. intermedia, we evaluated the effects of verapamil (VRP), reserpine (RSP), phe-arg β-naphthylamide dihydrochloride (PAβN) and carbonyl cyanide 3-chloro phenyl hydrazone (CCCP), four efflux pump inhibitors, on these colistin-resistant strains. Using the broth microdilution method, a CO and CCCP combination of 2 µg/mL and 10 µg/mL, respectively, significantly reduced the CO minimal inhibitory concentration (MIC) of B. intermedia, supporting an efflux pump mechanism. In contrast, VRP, PAβN and RSP did not restore CO susceptibility. A time kill assay showed a bactericidal effect of the CO–CCCP combination. Genomic analysis revealed a potential implication in the CO resistance mechanism of some conserved efflux pumps, such as YejABEF, NorM and EmrAB, as previously reported in other bacteria. An inhibitory effect of the CO–CCCP combination was observed on biofilm formation using the crystal violet method. These results suggest that the intrinsic CO resistance in Brucella intermedia is linked to an efflux pump mechanism and that the synergistic effect of CO–CCCP may open a new field to identify new treatments to restore antibiotic efficacy in humans.
Natural Killer Cell-Based Immunotherapy against Glioblastoma
Authors: Morimoto Takayuki , Nakazawa Tsutomu , Maeoka Ryosuke , Nakagawa Ichiro , Tsujimura Takahiro , Matsuda Ryosuke
Published: January 2023

Glioblastoma (GBM) is the most aggressive and malignant primary brain tumor in adults. Despite multimodality treatment involving surgical resection, radiation therapy, chemotherapy, and tumor-treating fields, the median overall survival (OS) after diagnosis is approximately 2 years and the 5-year OS is poor. Considering the poor prognosis, novel treatment strategies are needed, such as immunotherapies, which include chimeric antigen receptor T-cell therapy, immune checkpoint inhibitors, vaccine therapy, and oncolytic virus therapy. However, these therapies have not achieved satisfactory outcomes. One reason for this is that these therapies are mainly based on activating T cells and controlling GBM progression. Natural killer (NK) cell-based immunotherapy involves the new feature of recognizing GBM via differing mechanisms from that of T cell-based immunotherapy. In this review, we focused on NK cell-based immunotherapy as a novel GBM treatment strategy.
Deficiency of S100A9 Alleviates Sepsis-Induced Acute Liver Injury through Regulating AKT-AMPK-Dependent Mitochondrial Energy Metabolism
Authors: Zhang Yanting , Wu Feng , Teng Fei , Guo Shubin , Li Huihua
Published: January 2023

Acute liver injury (ALI) is recognized as a serious complication of sepsis in patients in intensive care units (ICUs). S100A8/A9 is known to promote inflammation and immune responses. However, the role of S100A8/A9 in the regulation of sepsis-induced ALI remains known. Our results indicated that S100A8/A9 expression was significantly upregulated in the livers of septic mice 24 h after cecal ligation and a puncture (CLP) operation. Moreover, S100A9-KO in mice markedly attenuated CLP-induced liver dysfunction and injury, promoting the AMPK/ACC/GLUT4-mediated increases in fatty acid and glucose uptake as well as the improvement in mitochondrial function and ATP production. In contrast, treatment with the AMPK inhibitor Compound C reversed the inhibitory effects of S100A9 KO on CLP-induced liver dysfunction and injury in vivo. Finally, the administration of the S100A9 inhibitor Paquinimod (Paq) to WT mice protected against CLP-induced mortality, liver injury and mitochondrial dysfunction. In summary, our findings demonstrate for the first time that S100A9 plays an important pro-inflammatory role in sepsis-mediated ALI by regulating AKT-AMPK-dependent mitochondrial energy metabolism and highlights that targeting S100A9 may be a promising new approach for the prevention and treatment of sepsis-related liver injury.
Circular RNAs as a Diagnostic and Therapeutic Target in Cardiovascular Diseases
Authors: Joaquim Victor Hugo Antonio , Pereira Noemy Pinto , Fernandes Tiago , Oliveira Edilamar Menezes
Published: January 2023

Circular RNAs (circRNAs) are a family of noncoding RNAs (ncRNAs) that are endogenous and widely distributed in different species, performing several functions, mainly their association with microRNAs (miRNAs) and RNA-binding proteins. CVDs remain the leading cause of death worldwide; therefore, the development of new therapies and strategies, such as gene therapies or nonpharmacological therapies, with low cost, such as physical exercise, to alleviate these diseases is of extreme importance for society. With increasing evidence of ncRNA participating in the progression of CVDs, several studies have reported these RNAs as promising targets for diagnosis and treatment. There are several studies of CVDs and the role of miRNAs and lncRNAs; however, little is known about the new class of RNAs, called circRNAs, and CVDs. In this mini review, we focus on the mechanisms of circRNAs and CVDs.
Single-Molecule Localization Microscopy of Presynaptic Active Zones in Drosophila melanogaster after Rapid Cryofixation
Authors: Mrestani Achmed , Lichter Katharina , Sirén Anna-Leena , Heckmann Manfred , Paul Mila M. , Pauli Martin
Published: January 2023

Single-molecule localization microscopy (SMLM) greatly advances structural studies of diverse biological tissues. For example, presynaptic active zone (AZ) nanotopology is resolved in increasing detail. Immunofluorescence imaging of AZ proteins usually relies on epitope preservation using aldehyde-based immunocompetent fixation. Cryofixation techniques, such as high-pressure freezing (HPF) and freeze substitution (FS), are widely used for ultrastructural studies of presynaptic architecture in electron microscopy (EM). HPF/FS demonstrated nearer-to-native preservation of AZ ultrastructure, e.g., by facilitating single filamentous structures. Here, we present a protocol combining the advantages of HPF/FS and direct stochastic optical reconstruction microscopy (dSTORM) to quantify nanotopology of the AZ scaffold protein Bruchpilot (Brp) at neuromuscular junctions (NMJs) of Drosophila melanogaster. Using this standardized model, we tested for preservation of Brp clusters in different FS protocols compared to classical aldehyde fixation. In HPF/FS samples, presynaptic boutons were structurally well preserved with ~22% smaller Brp clusters that allowed quantification of subcluster topology. In summary, we established a standardized near-to-native preparation and immunohistochemistry protocol for SMLM analyses of AZ protein clusters in a defined model synapse. Our protocol could be adapted to study protein arrangements at single-molecule resolution in other intact tissue preparations.
Identification of Genipin as a Potential Treatment for Type 2 Diabetes
Authors: Wu Yajun , Wang Yao , Liu Dongmin
Published: January 2023

The prevalence of type 2 diabetes (T2D) has been rising dramatically in many countries around the world. The main signatures of T2D are insulin resistance and dysfunction of β-cells. While there are several pharmaceutical therapies for T2D, no effective treatment is available for reversing the functional decline of pancreatic β-cells in T2D patients. It has been well recognized that glucagon-like peptide-1 (GLP-1), which is an incretin hormone secreted from intestinal L-cells, plays a vital role in regulating glycemic homeostasis via potentiating glucose-stimulated insulin secretion and promoting β-cell function. We found that genipin, a natural compound from Elli, can directly target intestinal L-cells, leading to the secretion of GLP-1. Incubation of the cells with genipin elicited a rapid increase in intracellular Ca2+. Inhibition of PLC ablated genipin-stimulated Ca2+ increase and GLP-1 secretion, suggesting that genipin-induced GLP-1 release from cells is dependent on the PLC/Ca2+ pathway. In vivo, acute administration of genipin stimulated GLP-1 secretion in mice. Chronically, treatment with genipin via oral gavage at 50 mg/kg/day for 6 weeks reversed hyperglycemia and insulin resistance in high-fat-diet (HFD)-induced obese mice. Moreover, genipin alleviated the impaired lipid metabolism and decreased lipid accumulation in the liver of obese mice. These results suggest that naturally occurring genipin might potentially be a novel agent for the treatment of T2D and diet-induced fatty liver disease.
Tachykinin Receptor-Selectivity of the Potential Glioblastoma-Targeted Therapy, DOTA-[Thi8,Met(O2)11]-Substance P
Authors: Suthiram Janine , Pieters Ané , Mohamed Moosa Zulfiah , Zeevaart Jan Rijn , Sathekge Mike M. , Ebenhan Thomas , Anderson Ross C. , Newton Claire L.
Published: January 2023

Radiopharmaceutical development hinges on the affinity and selectivity of the biological component for the intended target. An analogue of the neuropeptide Substance P (SP), 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-[Thi8,Met(O2)11]-SP (DOTA-[Thi8,Met(O2)11]SP), in the theranostic pair [68Ga]Ga-/ [213Bi]Bi-DOTA-[Thi8,Met(O2)11]SP has shown promising clinical results in the treatment of inoperable glioblastoma. As the theranostic targeting component, modifications to SP that affect the selectivity of the resulting analogue for the intended target (neurokinin-1 receptor [NK1R]) could be detrimental to its therapeutic potential. In addition to other closely related tachykinin receptors (neurokinin-2 receptor [NK2R] and neurokinin-3 receptor [NK3R]), SP can activate a mast cell expressed receptor Mas-related G protein-coupled receptor subtype 2 (MRGPRX2), which has been implicated in allergic-type reactions. Therefore, activation of these receptors by SP analogues has severe implications for their therapeutic potential. Here, the receptor selectivity of DOTA-[Thi8,Met(O2)11]SP was examined using inositol phosphate accumulation assay in HEK293-T cells expressing NK1R, NK2R, NK3R or MRGPRX2. DOTA-[Thi8,Met(O2)11]SP had similar efficacy and potency as native SP at NK1R, but displayed greater NK1R selectivity. DOTA-[Thi8,Met(O2)11]SP was unable to elicit significant activation of the other tachykinin receptors nor MRGPRX2 at high concentrations nor did it display antagonistic behaviour at these receptors. DOTA-[Thi8,Met(O2)11]SP, therefore has high potency and selectivity for NK1R, supporting its potential for targeted theranostic use in glioblastoma multiforme and other conditions characterised by NK1R overexpression.
Genetic Variation, DIMBOA Accumulation, and Candidate Gene Identification in Maize Multiple Insect-Resistance
Authors: Niu Yining , Zhao Xiaoqiang , Chao Wun , Lu Peina , Bai Xiaodong , Mao Taotao
Published: January 2023

Maize seedlings contain high amounts of 2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA), and the effect of DIMBOA is directly associated with multiple insect-resistance against insect pests such as Asian corn borer and corn leaf aphids. Although numerous genetic loci for multiple insect-resistant traits have been identified, little is known about genetic controls regarding DIMBOA content. In this study, the best linear unbiased prediction (BLUP) values of DIMBOA content in two ecological environments across 310 maize inbred lines were calculated; and their phenotypic data and BLUP values were used for marker-trait association analysis. We identified nine SSRs that were significantly associated with DIMBOA content, which explained 4.30–20.04% of the phenotypic variation. Combined with 47 original genetic loci from previous studies, we detected 19 hot loci and approximately 11 hot loci (in Bin 1.04, Bin 2.00–2.01, Bin 2.03–2.04, Bin 4.00–4.03, Bin 5.03, Bin 5.05–5.07, Bin 8.01–8.03, Bin 8.04–8.05, Bin 8.06, Bin 9.01, and Bin 10.04 regions) supported pleiotropy for their association with two or more insect-resistant traits. Within the 19 hot loci, we identified 49 candidate genes, including 12 controlling DIMBOA biosynthesis, 6 involved in sugar metabolism/homeostasis, 2 regulating peroxidases activity, 21 associated with growth and development [(auxin-upregulated RNAs (SAUR) family member and v-myb avian myeloblastosis viral oncogene homolog (MYB)], and 7 involved in several key enzyme activities (lipoxygenase, cysteine protease, restriction endonuclease, and ubiquitin-conjugating enzyme). The synergy and antagonism interactions among these genes formed the complex defense mechanisms induced by multiple insect pests. Moreover, sufficient genetic variation was reported for DIMBOA performance and SSR markers in the 310 tested maize inbred lines, and 3 highly (DIMBOA content was 402.74–528.88 μg g−1 FW) and 15 moderate (DIMBOA content was 312.92–426.56 μg g−1 FW) insect-resistant genotypes were major enriched in the Reid group. These insect-resistant inbred lines can be used as parents in maize breeding programs to develop new varieties.
Application of Metal–Organic Frameworks (MOFs) in Environmental Biosystems
Authors: Zhang Lu , Zheng Qingwen , Zhang Zheng , Li Huidong , Liu Xue , Sun Jinzhi , Wang Ruiwen
Published: January 2023

Metal–organic frameworks (MOFs) are crystalline materials that are formed by self-assembling organic linkers and metal ions with large specific areas and pore volumes. Their chemical tunability, structural diversity, and tailor-ability make them adaptive to decorate many substrate materials, such as biomass-derived carbon materials, and competitive in many environmental biosystems, such as biofuel cells, bioelectrocatalysts, microbial metal reduction, and fermentation systems. In this review, we surmised the recent progress of MOFs and MOF-derived materials and their applications in environmental biosystems. The behavior of MOFs and MOF-derived materials in different environmental biosystems and their influences on performance are described. The inherent mechanisms will guide the rational design of MOF-related materials and lead to a better understanding of their interaction with biocomponents.
Effects of Oxidative Stress on the Autophagy and Apoptosis of Granulosa Cells in Broody Geese
Authors: Hou Li’E , Gu Tiantian , Weng Kaiqi , Zhang Yu , Zhang Yang , Chen Guohong , Xu Qi
Published: January 2023

Broodiness is an unfavorable trait associated with the cessation of egg laying. Studies have found that excessive granulosa cell apoptosis and autophagy occur during goose broodiness. Other studies have also confirmed that oxidative stress is an important cause of apoptosis and autophagy. However, whether oxidative stress occurs during goose broodiness and whether this oxidative stress causes apoptosis and autophagy have not been fully elucidated. In this study, we investigated the effects of oxidative stress on the autophagy and apoptosis of granulosa cells in broody geese. The results showed higher mRNA expression of genes related to antioxidative stress responses (GPX, SOD-1, SOD-2, COX-2, CAT and hsp70) in pre-broody and broody geese than in laying birds. In addition, increased levels of granulosa cell apoptosis and autophagy were observed in pre-broody geese than in laying geese. Additionally, granulosa cells treated with H2O2 exhibited increased apoptosis and autophagy in vitro, and these effects were responsible for goose granulosa cell death. Moreover, vitamin E treatment effectively protected granulosa cells from H2O2-induced oxidative stress by inhibiting ROS production. Correspondingly, granulosa cell apoptosis and autophagy were greatly alleviated by vitamin E treatment. Together, our results demonstrated serious oxidative stress and granulosa cell apoptosis and autophagy in broody geese, and oxidative stress promoted apoptosis and autophagy. Vitamin E alleviated the autophagy and apoptosis of granulosa cells by inhibiting oxidative stress.
A Combination of Caffeine Supplementation and Enriched Environment in an Alzheimer’s Disease Mouse Model
Authors: Stazi Martina , Zampar Silvia , Klafki Hans-Wolfgang , Meyer Thomas , Wirths Oliver
Published: January 2023

A variety of factors has been associated with healthy brain aging, and epidemiological studies suggest that physical activity and nutritional supplements such as caffeine may reduce the risk of developing dementia and, in particular, Alzheimer’s disease (AD) in later life. Caffeine is known to act as a cognitive enhancer but has been also shown to positively affect exercise performance in endurance activities. We have previously observed that chronic oral caffeine supplementation and a treatment paradigm encompassing physical and cognitive stimulation by enriched environment (EE) housing can improve learning and memory performance and ameliorate hippocampal neuron loss in the Tg4-42 mouse model of AD. Here, we investigated whether these effects were synergistic. To that end, previous findings on individual treatments were complemented with unpublished, additional data and analyzed in depth by ANOVA followed by Bonferroni multiple comparison post tests. We further evaluated whether plasma neurofilament light chain levels reflect neuropathological and behavioral changes observed in the experimental groups. While a treatment combining physical activity and caffeine supplementation significantly improved learning and memory function compared to standard-housed vehicle-treated Tg4-42 in tasks such as the Morris water maze, no major additive effect outperforming the effects of the single interventions was observed.
A Novel Cuticular Protein-like Cpr21L Is Essential for Nymph Survival and Male Fecundity in the Brown Planthopper
Authors: Chen Tongtong , Jiao Qiqi , Ye Chenglong , Wu Jiangen , Zheng Yuanyuan , Sun Chuanxin , Hao Peiying , Yu Xiaoping
Published: January 2023

Cuticular proteins (CPs) are a large family and perform a variety of functions. However, the physiological roles of cuticle protein 21-like (Cpr21L) in the brown planthopper (Nilaparvata lugens, BPH), one of the most destructive insect pests of rice, are largely unclear. In this study, Cpr21L was revealed to be expressed in both BPH nymphs and adults, and the mRNA expression level was much higher in male adults than female adults. Spatially, the expression of Cpr21L in the testis was higher than in the ovary. The RNA interference (RNAi) of Cpr21L seriously decreased nymph survival, and no individual survived 8 days post-dsCpr21L injection. The RNAi of Cpr21L in adults also decreased the fertility of males, especially in the dsCpr21L♂ × dsGFP♀ group. The average number of eggs laid by one female in this group significantly decreased by 50.1%, and the eggs’ hatchability decreased from 76.5% to 23.8% compared with the control (dsGFP♂ × dsGFP♀). Furthermore, observations under a stereomicroscope showed that the RNAi of Cpr21L severely impaired the development of the testes. Therefore, Cpr21L is essential for the nymphal survival and male fecundity of BPH, thus providing a possible target for pest control.
The Effect of Pretreatment on a PtCu/C Catalyst’s Structure and Functional Characteristics
Authors: Belenov Sergey , Nevelskaya Alina , Nikulin Alexey , Tolstunov Mikhail
Published: January 2023

This research focuses on studying the effects of various pretreatment types on a PtCu/C catalyst synthesized by the co-deposition of metal precursors. The treatment in a 1 M HNO3 solution for 1 h is shown to result in a slight increase in activity in the oxygen electroreduction reaction (both the mass activity and specific activity calculated for the value of the electrochemically active surface area). The sample obtained after the thermal treatment, which is carried out at 350 °C under an argon atmosphere for 1 h, demonstrates 1.7 times higher specific activity than the sample before the treatment. The durability testing results obtained by the stress testing method in a potential range of 0.6–1.4 V during 2000 cycles show that the PtCu/C catalysts after both the acid treatment and the thermal treatment are characterized by higher residual activity than the sample in the “as-prepared” state.
A Straightforward Cytometry-Based Protocol for the Comprehensive Analysis of the Inflammatory Valve Infiltrate in Aortic Stenosis
Authors: Álvarez-Heredia Pablo , Domínguez-del-Castillo José Joaquín , Reina-Alfonso Irene , Gutiérrez-González Carmen , Hassouneh Fakhri , Batista-Duharte Alexander , Trujillo-Aguilera Antonio , López-Romero Rosalía , Muñoz Ignacio , Solana Rafael , Pera Alejandra
Published: January 2023

Aortic stenosis (AS) is a frequent cardiac disease in old individuals, characterized by valvular calcification, fibrosis, and inflammation. Recent studies suggest that AS is an active inflammatory atherosclerotic-like process. Particularly, it has been suggested that several immune cell types, present in the valve infiltrate, contribute to its degeneration and to the progression toward stenosis. Furthermore, the infiltrating T cell subpopulations mainly consist of oligoclonal expansions, probably specific for persistent antigens. Thus, the characterization of the cells implicated in the aortic valve calcification and the analysis of the antigens to which those cells respond to is of utmost importance to develop new therapies alternative to the replacement of the valve itself. However, calcified aortic valves have been only studied so far by histological and immunohistochemical methods, unable to render an in-depth phenotypical and functional cell profiling. Here we present, for the first time, a simple and efficient cytometry-based protocol that allows the identification and quantification of infiltrating inflammatory leukocytes in aortic valve explants. Our cytometry protocol saves time and facilitates the simultaneous analysis of numerous surface and intracellular cell markers and may well be also applied to the study of other cardiac diseases with an inflammatory component.
Nanoparticle-Mediated Drug Delivery of Doxorubicin Induces a Differentiated Clonogenic Inactivation in 3D Tumor Spheroids In Vitro
Authors: Popescu Roxana Cristina , Kopatz Verena , Andronescu Ecaterina , Savu Diana Iulia , Doerr Wolfgang
Published: January 2023

Involvement of 3D tumor cell models in the in vitro biological testing of novel nanotechnology-based strategies for cancer management can provide in-depth information on the real behavior of tumor cells in complex biomimetic architectures. Here, we used polyethylene glycol-encapsulated iron oxide nanoparticles for the controlled delivery of a doxorubicin chemotherapeutic substance (IONPDOX), and to enhance cytotoxicity of photon radiation therapy. The biological effects of nanoparticles and 150 kV X-rays were evaluated on both 2D and 3D cell models of normal human keratinocytes (HaCaT) and tumor cells—human cervical adenocarcinoma (HeLa) and human squamous carcinoma (FaDu)—through cell survival. In all 2D cell models, nanoparticles were similarly internalized in a peri-nuclear pattern, but resulted in different survival capabilities following radiation treatment. IONP on normal keratinocytes showed a protective effect, but a cytotoxic effect for cancer cells. In 3D tumor cell models, IONPDOX were able to penetrate the cell spheroids towards the hypoxic areas. However, IONPDOX and 150 kV X-rays led to a dose-modifying factor DMFSF=0.1 = 1.09 ± 0.1 (200 µg/mL IONPDOX) in HeLa spheroids, but to a radioprotective effect in FaDu spheroids. Results show that the proposed treatment is promising in the management of cervical adenocarcinoma.
Fluid Biomarkers of Central Nervous System (CNS) Involvement in Myotonic Dystrophy Type 1 (DM1)
Authors: Rossi Salvatore , Silvestri Gabriella
Published: January 2023

Myotonic dystrophy type 1 (DM1), commonly known as Steinert’s disease (OMIM #160900), is the most common muscular dystrophy among adults, caused by an unstable expansion of a CTG trinucleotide repeat in the 3′ untranslated region (UTR) of DMPK. Besides skeletal muscle, central nervous system (CNS) involvement is one of the core manifestations of DM1, whose relevant cognitive, behavioral, and affective symptoms deeply affect quality of life of DM1 patients, and that, together with muscle and heart, may profoundly influence the global disease burden and overall prognosis. Therefore, CNS should be also included among the main targets for future therapeutic developments in DM1, and, in this regard, identifying a cost-effective, easily accessible, and sensitive diagnostic and monitoring biomarker of CNS involvement in DM1 represents a relevant issue to be addressed. In this mini review, we will discuss all the papers so far published exploring the usefulness of both cerebrospinal fluid (CSF) and blood-based biomarkers of CNS involvement in DM1. Globally, the results of these studies are quite consistent on the value of CSF and blood Neurofilament Light Chain (NfL) as a biomarker of CNS involvement, with less robust results regarding levels of tau protein or amyloid-beta.
Moderate Constraint Facilitates Association and Force-Dependent Dissociation of HA-CD44 Complex
Authors: Yao Ziyang , Wu Jianhua , Fang Ying
Published: January 2023

Binding of cell surface glycoprotein CD44 to hyaluronic acid (HA) is a key event for mediating cell adhesion, motility, metastasis, inflammatory responses and tumor development, but the regulation mechanism and its molecular basis under diverse mechanical constraints remain unclear. We herein investigated interaction of CD44 HABD (HA binding site domain) to HA through free and steered molecular dynamics (MD) simulations as well as atomic force microscope (AFM) measurement using different constraints on HA. The middle, two ends or both of the constrained HA chains were fixed for MD simulations, while one and two biotin–avidin linkage or physical absorption were used to immobilize HA on substrates for AFM experiments, to model HA chains with low, moderate and high HA flexibilities, respectively. We found that binding of CD44 to moderate fixed HA was possessed of a better thermo-stability, a lower mechanical strength and a higher dissociation probability, while higher adhesive frequency, smaller rupture force and shorter lifetime were assigned to CD44 on the two biotin-immobilized HA rather than one biotin-immobilized or physically absorbed HA on substrates, suggesting a moderate HA flexibility requirement in favor of association and force-induced dissociation of CD44-HA complex. Tensile-induced convex conformation of HA chain was responsible for reduction of complex mechano-stability and did inversely a shrunken CD44 HABD under stretching; transition from catch bond to slip bond governed CD44-HA interaction. This study uncovered the regulation mechanism and its molecular basis for CD44-HA affinity under diverse mechano-microenvironments and provided a new insight into CD44-HA interaction-mediated cell inflammatory responses and tumor development.
Guiding Drug Repositioning for Cancers Based on Drug Similarity Networks
Authors: Qin Shimei , Li Wan , Yu Hongzheng , Xu Manyi , Li Chao , Fu Lei , Sun Shibin , He Yuehan , Lv Junjie , He Weiming , Chen Lina
Published: January 2023

Drug repositioning aims to discover novel clinical benefits of existing drugs, is an effective way to develop drugs for complex diseases such as cancer and may facilitate the process of traditional drug development. Meanwhile, network-based computational biology approaches, which allow the integration of information from different aspects to understand the relationships between biomolecules, has been successfully applied to drug repurposing. In this work, we developed a new strategy for network-based drug repositioning against cancer. Combining the mechanism of action and clinical efficacy of the drugs, a cancer-related drug similarity network was constructed, and the correlation score of each drug with a specific cancer was quantified. The top 5% of scoring drugs were reviewed for stability and druggable potential to identify potential repositionable drugs. Of the 11 potentially repurposable drugs for non-small cell lung cancer (NSCLC), 10 were confirmed by clinical trial articles and databases. The targets of these drugs were significantly enriched in cancer-related pathways and significantly associated with the prognosis of NSCLC. In light of the successful application of our approach to colorectal cancer as well, it provides an effective clue and valuable perspective for drug repurposing in cancer.