bluuebunny/crossref_metadata_2025 huggingface dataset:
Attributes of Lactobacillus acidophilus as Effected by Carao (Cassia grandis) Pulp Powder
Authors: Marcia Jhunior , Aleman Ricardo Santos , Montero-Fernández Ismael , Martín-Vertedor Daniel , Manrique-Fernández Víctor , Moncada Marvin , Kayanush Aryana
Published: April 2023

This study aimed to examine the prebiotic effect of Carao (Cassia grandis) pulp powder on the probiotic characteristics of Lactobacillus acidophilus regarding the viability, enzymatic activity, lysozyme resistance, bile and acid tolerances, and tolerance to gastric juices. Carao powder was used at 0% (control), 1%, 2%, and 3% (w/v). Acid and lysozyme tolerance were determined at 0, 30, 60, 90, and 120 min of incubation, whereas bile tolerance was analyzed at 0, 4, and 8 h. The gastric juice tolerance was determined at pH 2, 3, 4, 5, and 7 during 0 and 30 min of incubation. The protease was evaluated at 0, 12, and 24 h of incubation. The bacterial viability experiment was carried out for 10 h, taking readings every hour. Low-acidity conditions were used, and no significant differences were found between the control and the different Carao concentrations added to the L. acidophilus viability study. The Carao samples at 2% and 3% had significantly (p < 0.05) higher counts for bile and lysozyme resistance and higher protease activity when compared to control samples. On the other hand, Carao addition did not impact bacterial viability, acid tolerance, and gastric juice resistance. Thus, Carao pulp powder at different concentrations could act as a prebiotic source to enhance the development of L. acidophilus during gastrointestinal digestion.
Growth Performance, Digestive Enzyme Activities, and Oxidative Stress Markers in the Proximal Intestine of European Sea Bass (Dicentrarchus labrax) Fed High Starch or Lipid Diets
Authors: García-Meilán Irene , Herrera-Muñoz Juan Ignacio , Ordóñez-Grande Borja , Fontanillas Ramón , Gallardo Ángeles
Published: April 2023

The effect of different main dietary compositions on growth, anticipatory digestive enzyme activities, and oxidative status was studied in the proximal intestine of juvenile European sea bass. A control diet (C, 44% protein, 17.6% lipid, and 20% starch), three diets with increasing starch levels to test protein sparing (P36S36, P40S29, and P43S24), and two diets with high lipid content (L20S13 and L22S7) were tested. After 20 weeks, growth, digestive enzyme activities, lipid peroxidation, antioxidant enzyme activities, and G6PDH activity were measured after a 24-h fast. Sea bass fed P43S24 and L20S13 maintained an oxidative status like C fish, up-regulated CAT activity, and adjusted anticipatory protease activity. Instead, the lipid peroxidation increased in the L22S7 group, although CAT activity increased, whereas anticipatory total protease activity was downregulated. P40S29 also triggered LPO and CAT activity, but G6PDH levels diminished significantly. Moreover, an up-regulation in digestive enzyme activities was found. Finally, P36S36 fish showed less antioxidant enzyme activity and G6PDH, although their LPO tended to increase and their lipase and α-amylase activities were upregulated. In conclusion, the inclusion of carbohydrates up to 24% or lipids up to 20% is possible for this species if protein requirements are met without negative effects on growth.
Identification of Keystone Species in Ecological Communities in the East China Sea
Authors: Wang Yin , Kindong Richard , Gao Chunxia , Wang Jiaqi
Published: April 2023

Keystone species are critical to preserving community stability and species diversity. Identifying key species and investigating their ecological regulation will help to prioritize important species and gain a better understanding of community stability mechanisms. It is based on this understanding that the present study tried to elucidate major keystone species in an important ecosystem in eastern Chinese waters. Therefore, data were collected from fisheries surveys conducted between 2016 and 2021 in the East China Sea. We identified Muraenesox cinereus, Leptochela gracilis, and Trichiurus lepturus as keystone species in the region based on the results of principal component analysis of ten network indices. The removal analysis performed suggested that the loss of keystone species might have a negative impact on the complexity and stability of the food web in the East China Sea. As a result, keystone species should be prioritized in marine ecosystems.
Effect of CSN3 Gene Polymorphism on the Formation of Milk Gels Induced by Physical, Chemical, and Biotechnological Factors
Authors: Kruchinin Aleksandr G. , Illarionova Elena E. , Galstyan Aram G. , Turovskaya Svetlana N. , Bigaeva Alana V. , Bolshakova Ekaterina I. , Strizhko Mariya N.
Published: April 2023

During the last decade, research into genetic markers in the casein gene cluster has been actively introduced in cattle breeding programs. A special interest has been paid to the polymorphism of the CSN3 gene, responsible for the expression of the k-casein, playing a key role in protein coagulation, interaction with whey proteins, stabilization, and aggregation of casein micelles. This paper aimed to determine the effect of CSN3 genetic polymorphism on acid; rennet; acid–rennet; heat- and acid-induced as well as heat- and calcium-induced coagulation in skimmed milk; and protein-standardized milk systems (UF, NF, RO, VE). The influence of polymorphic variants of the CSN3 gene on the coagulation ability of milk proteins was assessed by the particle size of casein micelles, protein retention factor in the clot, and coagulation ability (duration of induction period, mass coagulation period, dynamic viscosity in gel point). The correlation between CSN3 gene polymorphism and protein coagulation was revealed. Milk systems obtained from CSN3 BB milk were found to have the shortest duration of coagulation, formation of better gel strength values, and increased yield compared to CSN3 AA. This study will improve the efficiency of milk processing and optimize the technology of dairy product production.
The Properties of Different Starches under the Influence of Glucono-Delta-Lactone at Different Concentrations
Authors: Mohd Shukri Afirah , Cheng Lai-Hoong
Published: April 2023

In this study, glucono-delta-lactone (GDL), which is Generally Recognized as Safe (GRAS), was added to native starches to modify their physicochemical properties. The effects of GDL on the molecular weight, pasting properties, flow behavior, gel syneresis, and crystallization properties of potato, tapioca, and corn starches were investigated. GPC results showed that as the GDL concentration increased, the molecular weight of amylose increased, whereas that of amylopectin decreased. An analysis using the Rapid Visco Analyzer revealed that the addition of GDL improved the pasting properties of potato starch, with reduced peak viscosity and breakdown viscosity, and it also improved setback viscosity. On the other hand, tapioca starch degraded substantially after GDL addition, indicating a lower tendency for short-term retrogradation, as reflected in the lower setback viscosity. The effects of GDL on corn starch pasting properties were very similar to those observed for tapioca starch, but the changes were relatively subtle. In terms of flow behavior, GDL addition decreased and increased the flow index values of the potato and tapioca starch pastes, respectively. However, the effect of GDL addition on the flow index value of the corn starch paste was found to be insignificant. The results also showed that the percentage of syneresis under the influence of GDL depended on the starch botanical origin—that is, potato starch, 14–18%, tapioca starch, 10–13%, and corn starch, 17–20%—which was substantiated by crystallinity analysis. It was observed that GDL has the potential to be used for starch modification because it creates desirable functionalities with the advantage of being a green-labelled ingredient.
Canadian Free Sugar Intake and Modelling of a Reformulation Scenario
Authors: Bernstein Jodi T. , Christoforou Anthea K. , Ng Alena (Praneet) , Weippert Madyson , Mulligan Christine , Flexner Nadia , L’Abbe Mary R.
Published: April 2023

Recommendations suggest limiting the intake of free sugar to under 10% or 5% of calories in order to reduce the risk of negative health outcomes. This study aimed to examine Canadian free sugar intake and model how intakes change following the implementation of a systematic reformulation of foods and beverages to be 20% lower in free sugar. Additionally, this study aimed to examine how calorie intake might be impacted by this reformulation scenario. Canadians’ free sugar and calorie intakes were determined using free sugar and calorie data from the Food Label Information Program (FLIP) 2017, a Canadian branded food composition database, and applied to foods reported as being consumed in Canadian Community Health Survey—Nutrition (CCHS-Nutrition) 2015. A “counterfactual” scenario was modelled to examine changes in intake following the reformulation of foods to be 20% lower in free sugar. The overall mean free sugar intake was 12.1% of calories and was reduced to align with the intake recommendations at 10% of calories in the “counterfactual” scenario (p < 0.05). Calorie intake was reduced by 3.2% (60 calories) in the “counterfactual” scenario (p < 0.05). Although the overall average intake was aligned with the recommendations, many age/sex groups exceeded the recommended intake, even in the “counterfactual” scenario. The results demonstrate a need to reduce the intake of free sugar in Canada to align with dietary recommendations, potentially through reformulation. The results can be used to inform future program and policy decisions related to achieving the recommended intake levels of free sugar in Canada.
Development and Quality Evaluation of Rigatoni Pasta Enriched with Hemp Seed Meal
Authors: Axentii Marina , Stroe Silviu-Gabriel , Codină Georgiana Gabriela
Published: April 2023

Existing food trends and modern consumers’ nutritional preferences have led to a rising demand for plant-based sources of protein such as hemp seed meal and the possibility of consumption hemp-rich products, most often in wheat-based staple foods, such as pasta. Pasta, as a conventional food product, is widely consumed worldwide due to its nutritional value, long shelf life, easy preparation, versatility of uses and also relatively low cost, which has made this product popular over time. Five formulations of rigatoni-shaped pasta obtained by partial replacement of wheat grain flour with 5%, 10%, 15% and 20% hemp seed meal (HSM) were studied regarding the technological, physicochemical, textural, antioxidant and sensory properties of the pasta samples. The substitution of wheat flour with hemp seed meal (HSM) led to a slight increase in the cooking loss (CL) and optimal cooking time (OCT) compared to the control sample, while the water absorption (WA) and swelling index (SI) decreased during evaluation. The experimental results also showed a decrease in luminosity and fracturability, with an increased firmness of pasta dough. Moreover, the developed pasta showed a significant improvement in antioxidant capacity in terms of total phenolic content (TPC) and antioxidant activity (DPPH). The pasta samples with 15% and 20% HSM substitutes experienced a browning process due to the Maillard reactions during drying, as well as a color loss during cooking; however, the color changes did not affect the acceptability of the product. The partial replacement of wheat flour with hemp seed protein highlighted the possibility of developing a new innovative type of pasta that claims a functional benefit and presents an improved nutritional value, mainly due to the partial protein intake, as well as certain benefits for a human diet.
Antibiotic-Free Poultry Meat Consumption and Its Determinants
Authors: Mohammadi Hosein , Saghaian Sayed , Boccia Flavio
Published: April 2023

In recent decades, meat consumption has increased globally due to increased incomes. A consequence of increased red meat consumption has been the rise in greenhouse gas emissions and nutrition-related diseases. Consumption of antibiotic-free (ABF) poultry meat is a viable healthy and sustainable substitute that will cause less damage to humans and the environment in the long run. This study was undertaken due to the increasing importance of healthy food consumption to preventing nutrition-related diseases. The health food industry is still in its preliminary stages; for market development of organic broiler meat and movement toward sustainable production of ABF meat, the first necessary step is conducting empirical research on ABF poultry meat consumption and identifying factors that influence household consumption patterns of ABF poultry meat. Therefore, the objectives of this study were the investigation of factors affecting poultry meat consumption by consumers and ABF poultry meat preference. Comparing the results could reveal what percentage of consumers are able to buy healthier higher-priced antibiotic-free poultry meat. Data were collected from 360 completed questionnaires completed by households from the city of Mashhad, Iran via simple random sampling in 2021. To investigate the first objective, an ordered logit model was used. The results showed that age, the head of household’s education, awareness of the nutritional benefits of poultry meat, advertising, and family income were statistically significant determinants of poultry meat consumption. To investigate the second objective, since some consumers cannot buy ABF poultry meat due to the higher prices, we used a two-step Heckman model. The results showed that the awareness of the nutritional benefits of ABF poultry meat, the head of household’s education, monthly family income, and advertising had positive impacts, with prices having a negative impact on the amount of antibiotic-free poultry meat consumed by the households. Comparing the results of the two models revealed that only about 30% of consumers could buy ABF poultry meat, mainly due to the higher prices. This study recommends improving consumer awareness, targeted distribution of ABF poultry meat according to customers’ economic and demographic characteristics, affordable prices, and appropriate marketing tools for sustainable consumption of ABF poultry meat.
A Model-Free Finite-Time Control Technique for Synchronization of Variable-Order Fractional Hopfield-like Neural Network
Authors: Alsaade Fawaz W. , Al-zahrani Mohammed S. , Yao Qijia , Jahanshahi Hadi
Published: April 2023

Although the literature presents promising techniques for the control of integer-order systems, control and synchronizing fractional systems still need further improvement to ensure their robustness and convergence time. This study aims to address this issue by proposing a model-free and finite-time super-twisting control technique for a variable-order fractional Hopfield-like neural network. The proposed controller is enhanced with an intelligent observer to account for disturbances and uncertainties in the chaotic model of the Hopfield-like neural network. The controller is able to regulate the system even when its complex variable-order fractional dynamic is completely unknown. Moreover, the proposed technique guarantees finite-time convergence of the closed-loop system. First, the dynamics of the variable-order fractional Hopfield-like neural network are examined. Then, the control design is described and its finite-time stability is proven. The controller is then applied to the variable-order fractional system and tested under two different scenarios to evaluate its performance. The results of the simulations demonstrate the excellent performance of the proposed method in both scenarios.
A Novel Similarity Measure of Spatiotemporal Event Setting Sequences: Method Development and Case Study
Authors: Xu Fuyu , Beard Kate
Published: April 2023

Examining the similarity of event environments or surroundings—more precisely, settings—provides additional insight in analyzing event sequences, as it provides information about the context and potential common factors that may have influenced them. This article proposes a new similarity measure for event setting sequences, which involve the space and time in which events occur. While similarity measures for spatiotemporal event sequences have been studied, the settings and setting sequences have not yet been studied. While modeling event setting sequences, we consider spatial and temporal scales to define the bounds of the setting and incorporate dynamic variables alongside static variables. Using a matrix-based representation and an extended Jaccard index, we developed new similarity measures that allow for the use of all variable data types. We successfully used these similarity measures coupled with other multivariate statistical analysis approaches in a case study involving setting sequences and pollution event sequences associated with the same monitoring stations, which validate the hypothesis that more similar spatial-temporal settings or setting sequences may generate more similar events or event sequences. In conclusion, the developed similarity measures have wide application beyond the case study to other disciplinary contexts and geographical settings. They offer researchers a powerful tool for understanding different factors and their dynamics corresponding to occurrences of spatiotemporal event sequences.
Professional Self-Esteem of Turkish Midwifery Students: A Mixed-Methods Approach
Authors: Baykal Akmeşe Zehra , Yücel Ummahan
Published: April 2023

Professional self-esteem (PSE) is the individual’s judgment of worthiness formed regarding the self-attributions related to the individual’s profession. A well-developed PSE is important for midwives to be successful in their profession, have a strong sense of belonging, and see the profession as important and valuable. This study aims to determine the perception of PSE among midwifery students, explain how their perceptions are formed, and reveal how they perceive the midwifery profession and how the components that make up this perception determine their PSE. Students’ average PSE score was analyzed, and the study was conducted using an explanatory sequential, which is a mixed-method approach, to interpret the results of the questionnaire and comparative analysis in more detail through direct interviews with university midwifery program students in western Turkey. Quantitative data were collected using the Individual Data Collection Form and the Professional Self-Esteem Scale. One-way analysis variance and independent sample t-tests were used to analyze the quantitative data. The students with the highest and lowest scale scores from each class level were interviewed using a Semi-Structured Interview Form. Thematic analysis was applied to analyze the qualitative data. The mean PSES score was 117.51 ± 17.60. The t-test analysis result shows that there was a significant difference between the PSES score and choosing the midwifery department willingly, believing that they could perform the midwifery profession before and after starting the midwifery education (p < 0.05). Three main themes were obtained: the meaning of being a midwife, deciding to become a midwife, and the difficulties of being a midwife. It can be said that the main force behind the students’ belief that the difficulties of the midwifery profession can be overcome is their strong love for the midwifery profession and their internalization of its importance.
Biomechanics of Topspin Forehand Loop in Table Tennis: An Application of OpenSim Musculoskeletal Modelling
Authors: Zhu Ruizhe , Yang Xiaoyi , Chong Luis C. , Shao Shirui , István Bíró , Gu Yaodong
Published: April 2023

Topspin is one of the most attacking strokes in table tennis, and topspin forehand loop is an effective way to score. The aim of this study was to investigate the kinematics of the lower extremities in topspin forehand loop between different levels via OpenSim Musculoskeletal Modelling. Ten elite athletes (NL1) and ten medium athletes (NL2) performed the topspin forehand loop without muscle and joint injuries. An eight-camera Vicon motion capture system was used to measure the kinematics data. During the topspin forehand loop, the forward phase (FP) and the entire phase (EP) of the NL1 were significantly shorter than that of the NL2. In the sagittal plane, NL1 significantly had greater hip and ankle flexion and extension at range of motion (ROM) but less hip flexion and knee flexion at FP and less ankle flexion at BP than NL2. In the frontal plane, NL1 displayed less ROM in the hip joint and significantly less hip abduction ROM at the backward phase (BP). In the transverse plane, NL1 had a significantly greater ROM in the hip joint and displayed significantly less hip ROM at the BP. The level differences presented in this study could help table tennis athletes to improve performance and coaches to develop technical training.
Bacterial Vaginosis and Post-Operative Pelvic Infections
Authors: Ziogou Afroditi , Ziogos Eleftherios , Giannakodimos Ilias , Giannakodimos Alexios , Sifakis Stavros , Ioannou Petros , Tsiodras Sotirios
Published: April 2023

Bacterial vaginosis (BV) represents a condition in which the normal protective Lactobacilli, especially those that produce H2O2, are replaced by high quantities of facultative anaerobes, leading to gynecologic and obstetric post-operative complications. BV is an important cause of obstetric and gynecological adverse sequelae and it could lead to an increased risk of contracting sexually transmitted infections such as gonorrhea, genital herpes, Chlamydia, Trichomonas, and human immunodeficiency virus. Herein, we reviewed bacterial vaginosis and its association with post-operative pelvic infections. In Obstetrics, BV has been associated with increased risk of preterm delivery, first-trimester miscarriage in women undergoing in vitro fertilization, preterm premature rupture of membranes, chorioamnionitis, amniotic fluid infections, postpartum and postabortal endomyometritis as well as postabortal pelvic inflammatory disease (PID). In gynecology, BV increases the risk of post-hysterectomy infections such as vaginal cuff cellulitis, pelvic cellulitis, pelvic abscess, and PID. BV is often asymptomatic, can resolve spontaneously, and often relapses with or without treatment. The American College of Obstetricians and Gynecologists recommends testing for BV in women having an increased risk for preterm delivery. Women with symptoms should be evaluated and treated. Women with BV undergoing gynecological surgeries must be treated to reduce the frequency of post-operative pelvic infections. Metronidazole and clindamycin are the mainstays of therapy. Currently, there is no consensus on pre-surgery screening for BV; decisions are made on a case-by-case basis.
Analysis of Digitized 3D Models Published by Archaeological Museums
Authors: Hernández-Muñoz Óscar
Published: April 2023

Nowadays, many museums publish virtual versions of the artifacts they keep in their collections in different 3D model viewers available on the Internet. However, despite the wide experience that some of them have in this field, it is still possible to find many virtual models that do not meet the desirable requirements for their publication on the Internet, especially regarding the optimization of the mesh and color textures needed for greater efficiency in the visualization and downloading of 3D objects. In this study, a sample of virtual models of objects belonging to multiple archaeological museums from different countries is analyzed. We considered multiple characteristics of the models, such as the number of polygons that compose them, the quality of the meshes, filter effects applied during post-processing, etc. The results of this research indicate that it is still necessary to make a greater effort to improve the training and digital skills of the professionals in charge of the digitization process in this area of cultural heritage.
Morphogenesis Changes in Protocorm Development during Symbiotic Seed Germination of Dendrobium chrysotoxum (Orchidaceae) with Its Mycobiont, Tulasnella sp.
Authors: Gao Xinzhen , Wang Yu , Deng Die , Luo Yinling , Shao Shicheng , Luo Yan
Published: April 2023

The endangered epiphytic orchid, Dendrobium chrysotoxum, is known for its ornamental and medicinal uses. However, knowledge of this orchid’s symbiotic seed germination, protocorm anatomy, and developmental morphology is completely unknown. In this study, we investigated the process of protocorm development of D. chrysotoxum during symbiotic germination using anatomical technologies and scanning electron microscopy. There are six development stages that were morphologically and anatomically defined during symbiotic seed germination. The embryo transformed into a protocorm at stage two, and a protrusion developed from the top of the protocorm at stage three and elongated to form the cotyledon at stage four. The stem apical meristem (SAM) was initiated at stage three and well developed at stage four. The first leaf and the root appeared at stages five and six, respectively. The hyphae entered through the micropylar end of the seed at stage one and then invaded the protocorm through rhizoids when rhizoids formed. Invading fungal hyphae colonized the inner cortex at the base of protocorms, formed pelotons, and were digested by host cells later. We conclude that protocorm development is programmed by the embryo, which determines the structure and function of the protocorm. The two developmental zones in a polarized D. chrysotoxum embryo include the smaller cells zone, which forms the cotyledon and a shoot apical meristem at the apical end, and the larger cells zone, which forms the mycorrhiza to house the symbiont at the basal end. These results will provide important insights for further research on the mechanisms underlying orchid-fungi symbiosis and enhance the understanding of orchid evolution.
Dealing with Intimate Partner Violence and Family Violence in a Regional Centre of Western Australia: A Study of the Knowledge, Attitudes, and Practices of Local Social Workers
Authors: Pelkowitz Lindi , Crossley Caroline , Greville Heath , Thompson Sandra C.
Published: April 2023

In the Midwest region of Western Australia, rates of intimate partner and family violence (IPV/FV) are high. We undertook research into social workers’ knowledge, attitudes, and skills as part of addressing this significant public health issue. Social workers come into contact with people experiencing IPV/FV in multiple settings, so their understandings and responses are critical to the prevention and interventions related to violence against women. The goal of the research was to determine the issues that the social workers in this region needed to be addressed that could assist in tackling the problem of IPV/FV. A questionnaire included open-ended questions to capture information on respondents’ profiles, knowledge, attitudes, practices, and education around IPV/FV, with 29 of 37 social workers working in the region responding. We also elicited respondents' recommendations related to training and service delivery. Despite working in many settings, most social workers had contact with people experiencing IPV/FV and had reasonable confidence and knowledge that showed an understanding of the complexity of FV, including why women stay in violent relationships. This paper identified social workers’ need for more education, including during their university training, resources, and service coordination to support best practice delivery of services to people affected by IPV/FV. Training to develop skills for conversations about IPV/FV with clients, around safety planning, and greater access to safe alternative accommodation for those leaving FV were identified priorities.
Perspectives on the Person-Centered Practice of Healthcare Professionals at an Inpatient Hospital Department: A Descriptive Study
Authors: Vareta Diana Alves , Oliveira Célia , Família Carlos , Ventura Filipa
Published: April 2023

The characteristics of health professionals and their understanding of person-centeredness may have important implications for the development of person-centered practice in specific care settings. In this study, we characterized the perceptions of the person-centered practice of a multidisciplinary team of health professionals working in the internal medicine inpatient unit of a Portuguese hospital. Data were collected using a brief sociodemographic and professional questionnaire and the person-centered practice inventory-staff (PCPI-S), and the effect of different sociodemographic and professional variables on each PCPI-S domain was determined using an analysis of variance (ANOVA). The results showed that a person-centered practice was positively perceived in the major constructs of prerequisites (M = 4.12; SD = 0.36), the practice environment (M = 3.50; SD = 0.48), and person-centered process (M = 4.08; SD = 0.62) domains. The highest scored construct was developed interpersonal skills (M = 4.35; SD = 0.47), and the lowest was supportive organization systems (M = 3.08; SD = 0.80). Gender was found to influence the perceptions of knowing self (F(2,75) = 3.67, p = 0.03, partial η2 = 0.089) and the physical environment (F(2,75) = 3.63, p = 0.03, partial η2 = 0.088), as was profession on shared decision-making systems (F(2,75) = 5.38, p < 0.01, partial η2 = 0.125) and commitment to the job (F(2,75) = 5.27, p < 0.01, partial η2 = 0.123), and the educational level on being professionally competent (F(1,75) = 4.99, p = 0.03, partial η2 = 0.062) and having commitment to the job (F(2,75) = 4.49, p = 0.04, partial η2 = 0.056). In addition, the PCPI-S proved to be a reliable instrument for characterizing healthcare professionals’ perceptions of the person-centeredness of care in this context. Identifying personal and professional variables that influence these perceptions could provide a starting point for defining strategies to move practice toward person-centeredness and for monitoring changes in healthcare practice.
Metabolic Effects of New Glucose Transporter (GLUT-1) and Lactate Dehydrogenase-A (LDH-A) Inhibitors against Chemoresistant Malignant Mesothelioma
Authors: Franczak Marika A. , Krol Oliwia , Harasim Gabriela , Jedrzejewska Agata , Zaffaroni Nadia , Granchi Carlotta , Minutolo Filippo , Avan Amir , Giovannetti Elisa , Smolenski Ryszard T. , Peters Godefridus J.
Published: April 2023

Malignant mesothelioma (MM) is a highly aggressive and resistant tumor. The prognostic role of key effectors of glycolytic metabolism in MM prompted our studies on the cytotoxicity of new inhibitors of glucose transporter type 1 (GLUT-1) and lactate dehydrogenase-A (LDH-A) in relation to ATP/NAD+ metabolism, glycolysis and mitochondrial respiration. The antiproliferative activity of GLUT-1 (PGL13, PGL14) and LDH-A (NHI-1, NHI-2) inhibitors, alone and in combination, were tested with the sulforhodamine-B assay in peritoneal (MESO-II, STO) and pleural (NCI-H2052 and NCI-H28) MM and non-cancerous (HMEC-1) cells. Effects on energy metabolism were measured by both analysis of nucleotides using RP-HPLC and evaluation of glycolysis and respiration parameters using a Seahorse Analyzer system. All compounds reduced the growth of MM cells in the µmolar range. Interestingly, in H2052 cells, PGL14 decreased ATP concentration from 37 to 23 and NAD+ from 6.5 to 2.3 nmol/mg protein. NHI-2 reduced the ATP/ADP ratio by 76%. The metabolic effects of the inhibitors were stronger in pleural MM and in combination, while in HMEC-1 ATP reduction was 10% lower compared to that of the H2052 cells, and we observed a minor influence on mitochondrial respiration. To conclude, both inhibitors showed cytotoxicity in MM cells, associated with a decrease in ATP and NAD+, and were synergistic in the cells with the highest metabolic modulation. This underlines cellular energy metabolism as a potential target for combined treatments in selected cases of MM.
Acute Downregulation but Not Genetic Ablation of Murine MCU Impairs Suppressive Capacity of Regulatory CD4 T Cells
Authors: Jost Priska , Klein Franziska , Brand Benjamin , Wahl Vanessa , Wyatt Amanda , Yildiz Daniela , Boehm Ulrich , Niemeyer Barbara A. , Vaeth Martin , Alansary Dalia
Published: April 2023

By virtue of mitochondrial control of energy production, reactive oxygen species (ROS) generation, and maintenance of Ca2+ homeostasis, mitochondria play an essential role in modulating T cell function. The mitochondrial Ca2+ uniporter (MCU) is the pore-forming unit in the main protein complex mediating mitochondrial Ca2+ uptake. Recently, MCU has been shown to modulate Ca2+ signals at subcellular organellar interfaces, thus fine-tuning NFAT translocation and T cell activation. The mechanisms underlying this modulation and whether MCU has additional T cell subpopulation-specific effects remain elusive. However, mice with germline or tissue-specific ablation of Mcu did not show impaired T cell responses in vitro or in vivo, indicating that ‘chronic’ loss of MCU can be functionally compensated in lymphocytes. The current work aimed to specifically investigate whether and how MCU influences the suppressive potential of regulatory CD4 T cells (Treg). We show that, in contrast to genetic ablation, acute siRNA-mediated downregulation of Mcu in murine Tregs results in a significant reduction both in mitochondrial Ca2+ uptake and in the suppressive capacity of Tregs, while the ratios of Treg subpopulations and the expression of hallmark transcription factors were not affected. These findings suggest that permanent genetic inactivation of MCU may result in compensatory adaptive mechanisms, masking the effects on the suppressive capacity of Tregs.
Facile Synthesis of Sulfur-Containing Functionalized Disiloxanes with Nonconventional Fluorescence by Thiol–Epoxy Click Reaction
Authors: Tang Jing , Feng Shengyu , Wang Dengxu
Published: April 2023

Herein, a series of novel sulfur-containing functionalized disiloxanes based on a low-cost and commercially available material, i.e., 1,3-bis(3-glycidoxypropyl)-1,1,3,3-tetramethyldisiloxane, and various thiol compounds were prepared by thiol–epoxy click reaction. It was found that both lithium hydroxide (LiOH) and tetrabutylammonium fluoride (TBAF) have high catalytic activity after optimizing the reaction condition, and the reaction can be carried out with high yields, excellent regioselectivity, mild reaction condition, and good tolerance of functional groups. These compounds exhibit excellent nonconventional fluorescence due to the formation of coordination bonds between Si atoms and heteroatoms (e.g., S or N) and can emit blue fluorescence upon ultraviolet (UV) irradiation. These results demonstrate that the thiol–epoxy click reaction could promisingly act as an efficient organosilicon synthetic methodology to construct various organosilicon materials with novel structures and functionality, and thus their application scope will be significantly expanded.
Neuropilin-1 Knockout and Rescue Confirms Its Role to Promote Metastasis in MDA-MB-231 Breast Cancer Cells
Authors: Al-Zeheimi Noura , Gao Yan , Greer Peter A. , Adham Sirin A.
Published: April 2023

Breast cancer (BC) metastasis remains a leading cause of female mortality. Neuropilin-1 (NRP-1) is a glycoprotein receptor that plays ligand-dependent roles in BC. Clinical studies indicate its correlation with metastatic disease; however, its functional role in BC metastasis remains uncertain. CRISPR-Cas9 was used to knockout the NRP-1 gene in MDA-MB-231 BC cells, and the effects on metastasis were determined using an orthotopic mouse engraftment model. NRP-1 expression in knockout cells was rescued using a recombinant cDNA with a silent mutation in the sgRNA target-adjacent PAM sequence. Differentially expressed genes between NRP-1 knockout and control cells were determined using whole-transcriptome sequencing and validated using real-time PCR. NRP-1KO cells showed a pronounced reduction in the metastasis to the lungs. KEGG pathway analysis of the transcriptome data revealed that PI3K and ECM receptor interactions were among the top altered pathways in the NRP-1KO cells. In addition, reduction in metastasis enhancers proteins, Integrin-β3 and Tenascin-C, and genes CCL20 and FN1 and upregulation of metastasis suppressor genes, ACVRL and GPX3 in NRP-1KO were detected. These findings provide evidence for a functional role for NRP-1 in BC metastasis, supporting further exploration of NRP-1 and the identified genes as targets in treating metastatic BC.
Deoxynivalenol Mycotoxin Inhibits Rabies Virus Replication In Vitro
Authors: Liu Qian , He Qing , Zhu Wuyang
Published: April 2023

Rabies is a highly fatal disease, and it is vital to find effective ways to manage and control infection. There is a need for new effective antiviral drugs that are particularly effective treatments for rabies. Deoxynivalenol (DON) is known mainly for its toxicity, but at the molecular level, it can inhibit RNA and DNA replication, and there is increasing evidence that different doses of DON have a positive effect on inhibiting virus replication. Based on this, we evaluated the effect of DON on inhibiting the rabies virus in vitro. The inhibitory effect of DON on rabies virus activity was dose- and time-dependent, and 0.25 μg/mL of DON could inhibit 99% of rabies virus activity within 24 h. Furthermore, DON could inhibit the adsorption, entry, replication, and release of rabies virus but could not inactivate the virus. The inhibitory effect of DON on rabies virus may be achieved by promoting apoptosis. Our study provides a new perspective for the study of anti-rabies virus and expands the direction of action of mycotoxins.
Biomolecular and Biohybrid Systems for Solar Energy Conversion
Authors: Kargul Joanna , Jacquet Margot
Published: April 2023

The depletion of fossil fuels and increased amount of atmospheric/environmental pollution associated with the excessive use of fossil fuels to power our economies have intensified the efforts of academia and industry worldwide to seek sustainable technological solutions to meet the global energy demand [...]
Mesenchymal Stem Cells in Nerve Tissue Engineering: Bridging Nerve Gap Injuries in Large Animals
Authors: Lischer Mirko , di Summa Pietro G. , Petrou Ilias G. , Schaefer Dirk J. , Guzman Raphael , Kalbermatten Daniel F. , Madduri Srinivas
Published: April 2023

Cell-therapy-based nerve repair strategies hold great promise. In the field, there is an extensive amount of evidence for better regenerative outcomes when using tissue-engineered nerve grafts for bridging severe gap injuries. Although a massive number of studies have been performed using rodents, only a limited number involving nerve injury models of large animals were reported. Nerve injury models mirroring the human nerve size and injury complexity are crucial to direct the further clinical development of advanced therapeutic interventions. Thus, there is a great need for the advancement of research using large animals, which will closely reflect human nerve repair outcomes. Within this context, this review highlights various stem cell-based nerve repair strategies involving large animal models such as pigs, rabbits, dogs, and monkeys, with an emphasis on the limitations and strengths of therapeutic strategy and outcome measurements. Finally, future directions in the field of nerve repair are discussed. Thus, the present review provides valuable knowledge, as well as the current state of information and insights into nerve repair strategies using cell therapies in large animals.
Visual Detection of Stem-Loop Primer Amplification (SPA) Products without Denaturation Using Peroxidase-like DNA Machines (PxDM)
Authors: Maltzeva Yulia I. , Gorbenko Daria A. , Nikitina Ekaterina V. , Rubel Maria S. , Kolpashchikov Dmitry M.
Published: April 2023

Rapid, inexpensive, and accurate determination of nucleic acids is a decisive factor in evaluating population’s health and monitoring treatment at point-of-care (POC) settings. Testing systems with visual outputs can provide instrument-free signal detection. Isothermal amplification technologies can substitute conventional polymerase chain reaction (PCR) testing due to compatibility with the POC diagnostic. Here, we have visually detected DNA fragments obtained by stem-loop-primer-assisted isothermal amplification (SPA), but not those obtained by PCR or LAMP amplification using DNA nanomachines with peroxidase-like activity (PxDM) with sensitivity to a single nucleotide substitution. Compared to the diagnostics with conventional loop-mediated isothermal amplification (LAMP), the PxDM method produces no false positive signals with the non-specific amplification products. The study suggests that PxDM, in conjunction with SPA isothermal amplification, can become a valid platform for POC testing systems.
Local Inflammatory Mediators Involved in Neuropathic Pain
Authors: García-Fernández Patricia , Reinhold Colette , Üçeyler Nurcan , Sommer Claudia
Published: April 2023

Polyneuropathy (PNP) is a term to describe diseases of the peripheral nervous system, 50% of which present with neuropathic pain. In some types of PNP, pain is restricted to the skin distally in the leg, suggesting a local regulatory process leading to pain. In this study, we proposed a pro-inflammatory pathway mediated by NF-κB that might be involved in the development of pain in patients with painful PNP. To test this hypothesis, we have collected nerve and skin samples from patients with different etiologies and levels of pain. We performed RT-qPCR to analyze the gene expression of the proposed inflammatory pathway components in sural nerve and in distal and proximal skin samples. In sural nerve, we showed a correlation of TLR4 and TNFα to neuropathic pain, and an upregulation of TNFα in patients with severe pain. Patients with an inflammatory PNP also presented a lower expression of TRPV1 and SIRT1. In distal skin, we found a reduced expression of TLR4 and miR-146-5p, in comparison to proximal skin. Our findings thus support our hypothesis of local inflammatory processes involved in pain in PNP, and further show disturbed anti-inflammatory pathways involving TRPV1 and SIRT1 in inflammatory PNP.
Metal-Organic Framework (MOF)—A Universal Material for Biomedicine
Authors: Vodyashkin Andrey A. , Sergorodceva Antonina V. , Kezimana Parfait , Stanishevskiy Yaroslav M.
Published: April 2023

Metal-organic frameworks (MOFs) are a very promising platform for applications in various industries. In recent years, a variety of methods have been developed for the preparation and modification of MOFs, providing a wide range of materials for different applications in life science. Despite the wide range of different MOFs in terms of properties/sizes/chemical nature, they have not found wide application in biomedical practices at present. In this review, we look at the main methods for the preparation of MOFs that can ensure biomedical applications. In addition, we also review the available options for tuning the key parameters, such as size, morphology, and porosity, which are crucial for the use of MOFs in biomedical systems. This review also analyses possible applications for MOFs of different natures. Their high porosity allows the use of MOFs as universal carriers for different therapeutic molecules in the human body. The wide range of chemical species involved in the synthesis of MOFs makes it possible to enhance targeting and prolongation, as well as to create delivery systems that are sensitive to various factors. In addition, we also highlight how injectable, oral, and even ocular delivery systems based on MOFs can be used. The possibility of using MOFs as therapeutic agents and sensitizers in photodynamic, photothermal, and sonodynamic therapy was also reviewed. MOFs have demonstrated high selectivity in various diagnostic systems, making them promising for future applications. The present review aims to systematize the main ways of modifying MOFs, as well as the biomedical applications of various systems based on MOFs.
Impact of the Remission of Type 2 Diabetes on Cardiovascular Structure and Function, Exercise Capacity and Risk Profile: A Propensity Matched Analysis
Authors: Bilak Joanna M. , Yeo Jian L. , Gulsin Gaurav S. , Marsh Anna-Marie , Sian Manjit , Dattani Abhishek , Ayton Sarah L. , Parke Kelly S. , Bain Moira , Pang Wenjie , Boulos Sherif , Pierre Tim G. St , Davies Melanie J. , Yates Thomas , McCann Gerry P. , Brady Emer M.
Published: April 2023

Type 2 diabetes (T2D) confers a high risk of heart failure frequently with evidence of cardiovascular structural and functional abnormalities before symptom onset. The effects of remission of T2D on cardiovascular structure and function are unknown. The impact of the remission of T2D, beyond weight loss and glycaemia, on cardiovascular structure and function and exercise capacity is described. Adults with T2D without cardiovascular disease underwent multimodality cardiovascular imaging, cardiopulmonary exercise testing and cardiometabolic profiling. T2D remission cases (Glycated hemoglobin (HbA1c) < 6.5% without glucose-lowering therapy, ≥3 months) were propensity score matched 1:4 based on age, sex, ethnicity and time of exposure to those with active T2D (n = 100) with the nearest-neighbour method and 1:1 with non-T2D controls (n = 25). T2D remission was associated with a lower leptin–adiponectin ratio, hepatic steatosis and triglycerides, a trend towards greater exercise capacity and significantly lower minute ventilation/carbon dioxide production (VE/VCO2 slope) vs. active T2D (27.74 ± 3.95 vs. 30.52 ± 5.46, p < 0.0025). Evidence of concentric remodeling remained in T2D remission vs. controls (left ventricular mass/volume ratio 0.88 ± 0.10 vs. 0.80 ± 0.10, p < 0.025). T2D remission is associated with an improved metabolic risk profile and ventilatory response to exercise without concomitant improvements in cardiovascular structure or function. There is a requirement for continued attention to risk factor control for this important patient population.
Challenges of Treating ADHD with Comorbid Substance Use Disorder: Considerations for the Clinician
Authors: Barbuti Margherita , Maiello Marco , Spera Vincenza , Pallucchini Alessandro , Brancati Giulio , Maremmani Angelo , Perugi Giulio , Maremmani Icro
Published: April 2023

Adults with attention deficit/hyperactivity disorder (ADHD) often present psychiatric comorbidities and, in particular, substance use disorder (SUD). ADHD-SUD comorbidity is characterized by greater severity of both disorders, earlier age of onset, higher likelihood of polydrug-abuse and suicidal behaviors, more hospitalizations, and lower treatment adherence. At the present stage, research focused on the pharmacological management of ADHD with comorbid SUD in both adolescents and adults is still lacking. Furthermore, while the short-term effects of stimulants are well studied, less is known about the chronic effects of these drugs on dopamine signaling. Current available evidence is consistent in reporting that high doses of stimulant medications in ADHD-SUD subjects have a mild to moderate efficacy on ADHD symptoms. Some data suggest that pharmacological treatment with stimulants may be beneficial for both ADHD symptoms and comorbid cocaine or amphetamine use. However, in the long run, stimulant medications may have a potential risk for misuse. For the absence of potential misuse, atomoxetine is often recommended for ADHD with comorbid cocaine or amphetamine use disorder. However, its efficacy in reducing addictive behavior is not demonstrated. In subjects with other subtypes of SUD, both atomoxetine and stimulant drugs seem to have scarce impact on addictive behavior, despite the improvement in ADHD symptomatology. In this population, ADHD treatment should be combined with SUD-specific strategies.