bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of a 5-week therapeutic massage on erector spinae and upper trapezius muscle stiffness as determined by shear-wave elastography: a randomized controlled trial
Authors: Jelen Amadej , Javornik Erina , Meh Sara Gloria , Kozinc Žiga
Published: August 2024

Introduction

Massage is an effective treatment for reducing pain, swelling, stiffness, and improving muscle mobility. Although self-reported benefits on muscle stiffness and pain are well-known, studies measuring muscle stiffness objectively are scarce.

Methods

A randomized controlled trial involving 30 recreationally active young women (22.3 ± 0.4 years) was conducted. The participants were randomly assigned to either the control group or the intervention group which received a series of five 30-min whole back therapeutic massage sessions over 5 weeks. Shear wave elastography was used to assess muscle stiffness (erector spinae (ESp) and upper trapezius (UT) muscles) before and after the intervention and at 3-week follow-up.

Results

For ESp, there was no statistically significant time × group interaction (F = 2.908; p = 0.063). However, there was a statistically significant and large time × group interaction for UT (F = 13.533; p = 0.006; η2 = 0.19). Post-hoc testing for time indicated that the shear modulus in the intervention group was reduced at follow-up (p = 0.005; d = 1.02), while the difference between baseline and post-intervention measurements were not statistically significant (p = 0.053; d = 0.75).

Conclusion

In conclusion, massage significantly reduced proximal UT stiffness both 3 days and 3 weeks after the intervention. However, it had no significant effect on the distal part of UT or the ESp muscle.
Building a solid foundation: advancing evidence synthesis in agri-food systems science
Authors: Ellssel Pierre , Küstner Georg , Kaczorowska-Dolowy Magdalena , Vázquez Eduardo , Di Bene Claudia , Li Honghong , Brizuela-Torres Diego , Elangovan Vennila Elansurya , Vicente-Vicente José Luis , Avila-Ortega Daniel Itzamna
Published: August 2024

Enhancing the reliability of literature reviews and evidence synthesis is crucial for advancing the transformation of agriculture and food (agri-food) systems as well as for informed decisions and policy making. In this perspective, we argue that evidence syntheses in the field of agri-food systems research often suffer from a suite of methodological limitations that substantially increase the risk of bias, i.e., publication and selection bias, resulting in unreliable and potentially flawed conclusions and, consequently, poor decisions (e.g., policy direction, investment, research foci). We assessed 926 articles from the Collaboration for Environmental Evidence Database of Evidence Reviews (CEEDER) and recent examples from agri-food systems research to support our reasoning. The analysis of articles from CEEDER (n = 926) specifically indicates poor quality (Red) in measures to minimize subjectivity during critical appraisal (98% of all reviews), application of the eligibility criteria (97%), cross-checking of extracted data by more than one reviewer (97%), critical appraisal of studies (88%), establishment of an a priori method/protocol (86%), and transparent reporting of eligibility decisions (65%). Additionally, deficiencies (Amber) were found in most articles (>50%) regarding the investigation and discussion of variability in study findings (89%), comprehensiveness of the search (78%), definition of eligibility criteria (72%), search approach (64%), reporting of extracted data for each study (59%), consideration and discussion of the limitations of the synthesis (56%), documentation of data extraction (54%) and regarding the statistical approach (52%). To enhance the quality of evidence synthesis in agri-food science, review authors should use tried-and-tested methodologies and publish peer-reviewed a priori protocols. Training in evidence synthesis methods should be scaled, with universities playing a crucial role. It is the shared duty of research authors, training providers, supervisors, reviewers, and editors to ensure that rigorous and robust evidence syntheses are made available to decision-makers. We argue that all these actors should be cognizant of these common mistakes to avoid publishing unreliable syntheses. Only by thinking as a community can we ensure that reliable evidence is provided to support appropriate decision-making in agri-food systems science.
Ribosomal protein L32 contributes to the growth, antibiotic resistance and virulence of Glaesserella parasuis
Authors: Chen Qiaodan , Yu Bin , Su Fei , Ye Shiyi , Xu Lihua , Yuan Xiufang , Wu Shumin , Zhang Hui , Li Junxing
Published: August 2024

Glaesserella parasuis is the pathogen that causes Glässer’s disease in pigs, which is characterized by fibrinous polyserositis, arthritis and meningitis. Research on ribosomal protein L32 in microorganisms has mainly focused on regulating gene transcription and translation, but its effect on bacterial virulence is unclear. The role of L32 gene in G. parasuis is not clear, and in order to study the function of L32 gene, a suicide plasmid-mediated natural transformation method was used to construct a L32 gene deletion mutant. We found that although L32 was shown to be non-essential for cell proliferation, the growth curve of ΔL32 is clearly different compared with that of ZJ1208. ΔL32 produced more outer membrane vesicles (OMVs) with a variety of irregular shapes, but produced similar biofilm to the parental strain. ΔL32 is more sensitive to osmotic pressure, oxidation pressure and heat shock stress. Meanwhile, ΔL32 is significantly more susceptible to antimicrobials such as spectinomycin, apramycin, sulfafurazole, but not to other antibiotics used in this study. In the mouse challenge experiment, the mortality of mice infected with the mutant strain decreased by 40% compared to those infected with the wild-type strain, indicating that L32 is a virulence-associated factor which contributes to bacterial fitness in host environments. The above results show that L32 is important for the growth, stress resistance and virulence of G. parasuis, and this study also confirms for the first time that L32 plays an important role in antibiotic resistance against aminoglycosides and sulfonamides.
Impact of swine influenza A virus on porcine reproductive and respiratory syndrome virus infection in alveolar macrophages
Authors: Grevelinger Janaïna , Bourry Olivier , Meurens François , Perrin Aline , Hervet Caroline , Dubreil Laurence , Simon Gaëlle , Bertho Nicolas
Published: August 2024

Porcine respiratory disease complex represents a major challenge for the swine industry, with swine influenza A virus (swIAV) and porcine reproductive and respiratory syndrome virus (PRRSV) being major contributors. Epidemiological studies have confirmed the co-circulation of these viruses in pig herds, making swIAV-PRRSV co-infections expected. A couple of in vivo co-infection studies have reported replication interferences between these two viruses. Herein, using a reductionist in vitro model, we investigated the potential mechanisms of these in vivo interferences. We first examined the impact of swIAV on porcine alveolar macrophages (AMs) and its effects on AMs co-infection by PRRSV. This was done either in monoculture or in co-culture with respiratory tracheal epithelial cells to represent the complexity of the interactions between the viruses and their respective target cells (epithelial cells for swIAV and AMs for PRRSV). AMs were obtained either from conventional or specific pathogen-free (SPF) pigs. SwIAV replication was abortive in AMs, inducing cell death at high multiplicity of infections. In AMs from three out of four conventional animals, swIAV showed no impact on PRRSV replication. However, inhibition of PRRSV multiplication was observed in AMs from one animal, accompanied by an early increase in the expression of interferon (IFN)-I and IFN-stimulated genes. In AMs from six SPF pigs, swIAV inhibited PRRSV replication in all animals, with an early induction of antiviral genes. Co-culture experiments involving tracheal epithelial cells and AMs from either SPF or conventional pigs all showed swIAV-induced inhibition of PRRSV replication, together with early induction of antiviral genes. These findings highlight the complex interactions between swIAV and PRRSV in porcine AMs, and would suggest a role of host factors, such as sanitary status, in modulating viral propagation. Our co-culture experiments demonstrated that swIAV inhibits PRRSV replication more effectively in the presence of respiratory tracheal epithelial cells, suggesting a synergistic antiviral response between AMs and epithelial cells, consistent with in vivo experiments.
Indoor Visible Light Fingerprint Location Method Based on Marine Predator Algorithm-Optimized Least Squares Support Vector Machine
Authors: Mei Yuanjia , Deng Yong
Published: August 2024

To increase the accuracy of indoor visible light positioning, a novel indoor visible light localization technique based on the marine predator algorithm-optimized least squares support vector machine (MPA-LSSVM) is suggested. The light signals of each reference point are recorded in the first place and a fingerprint database is created. Introduced thereafter is the marine predator algorithm, which, through iterative optimization of the hyperparameters of the least squares support vector machine, aims to establish an optimal localization model using finely-tuned hyperparameters. This culminated in the development of a positioning model, successfully attaining the objective of enhancing accuracy in positioning while minimizing time expenditure. In an indoor-positioning scene (size: 1 m × 1 m × 1 m), the average positioning error of the proposed positioning method is 0.041 m, and the proportion of test points with positioning errors less than 0.1 m is 96.7%.
FDG PET-CT for the Detection of Occult Nodal Metastases in Head and Neck Cancer: A Systematic Review and Meta-Analysis
Authors: Guedj Danaé , Neveü Sophie , Becker Minerva , Mermod Maxime
Published: August 2024

Because of an estimated 20–30% prevalence of occult lymph node (LN) metastases in patients with head and neck squamous cell carcinoma (HNSCC), neck dissection is often proposed, despite its potential morbidity. In this systematic review and meta-analysis, the diagnostic performance of FDG PET-CT in detecting occult LN metastases was evaluated in patients with clinically negative necks (cN0) and in whom histopathology of a neck dissection specimen served as gold standard. Overall, 16 studies out of 2062 screened on PubMed and EMBASE fulfilled the inclusion criteria (n = 1148 patients). Seven of these sixteen studies were split into two or three studies because they contained data that could be processed distinctly in our meta-analysis. For this reason, a total of 25 studies were identified and included in the analysis (n total = 1918 patients). The overall prevalence of metastatic nodes per patient was 22.67%. The pooled sensitivity, specificity, diagnostic odds ratios, and negative predictive value (NPV) were 0.71 (95%CI: 0.66–0.75), 0.90 (95%CI: 0.84–0.93), 20.03 (95%CI: 13.51–29.70), and 0.92 (95%CI: 0.89–0.95), respectively. The main causes of inter-study heterogeneity included different reference standards (evaluation per patient, per neck side, or per neck level). The current meta-analysis showed that FDG PET-CT has a high specificity and NPV for ruling out nodal involvement in cN0 necks, but a limited sensitivity.
Mutational Signatures in Colorectal Cancer: Translational Insights, Clinical Applications, and Limitations
Authors: Crisafulli Giovanni
Published: August 2024

A multitude of exogenous and endogenous processes have the potential to result in DNA damage. While the repair mechanisms are typically capable of correcting this damage, errors in the repair process can result in mutations. The findings of research conducted in 2012 indicate that mutations do not occur randomly but rather follow specific patterns that can be attributed to known or inferred mutational processes. The process of mutational signature analysis allows for the inference of the predominant mutational process for a given cancer sample, with significant potential for clinical applications. A deeper comprehension of these mutational signatures in CRC could facilitate enhanced prevention strategies, facilitate the comprehension of genotoxic drug activity, predict responses to personalized treatments, and, in the future, inform the development of targeted therapies in the context of precision oncology. The efforts of numerous researchers have led to the identification of several mutational signatures, which can be categorized into different mutational signature references. In CRC, distinct mutational signatures are identified as correlating with mismatch repair deficiency, polymerase mutations, and chemotherapy treatment. In this context, a mutational signature analysis offers considerable potential for enhancing minimal residual disease (MRD) tests in stage II (high-risk) and stage III CRC post-surgery, stratifying CRC based on the impacts of genetic and epigenetic alterations for precision oncology, identifying potential therapeutic vulnerabilities, and evaluating drug efficacy and guiding therapy, as illustrated in a proof-of-concept clinical trial.
Multifractal Hopscotch in Hopscotch by Julio Cortázar
Authors: Dec Jakub , Dolina Michał , Drożdż Stanisław , Kwapień Jarosław , Stanisz Tomasz
Published: August 2024

Punctuation is the main factor introducing correlations in natural language written texts and it crucially impacts their overall effectiveness, expressiveness, and readability. Punctuation marks at the end of sentences are of particular importance as their distribution can determine various complexity features of written natural language. Here, the sentence length variability (SLV) time series representing Hopscotch by Julio Cortázar are subjected to quantitative analysis with an attempt to identify their distribution type, long-memory effects, and potential multiscale patterns. The analyzed novel is an important and innovative piece of literature whose essential property is freedom of movement between its building blocks given to a reader by the author. The statistical consequences of this freedom are closely investigated in both the original, Spanish version of the novel, and its translations into English and Polish. Clear evidence of rich multifractality in the SLV dynamics, with a left-sided asymmetry, however, is observed in all three language versions as well as in the versions with differently ordered chapters.
Ten Years of Teaching Forgiveness Education in the Schools of Greece: Looking toward the Future
Authors: Galiti Peli
Published: August 2024

This article presents the accumulated experience and outcomes after ten years of forgiveness education (FE) in the schools of Greece. The author implemented the program throughout Greece by publishing new books on FE adapted to the Greek culture and training an interdisciplinary team of educators through both in-person and online workshops in several Greek cities. Using feedback from the experiences of the trained teachers and the participating students, a lot of valuable information was obtained for the future expansion of forgiveness education programs. Our objective is to provide a conceptual map for educators so that they may be better equipped when designing their own implementation plans for forgiveness education programs in other schools and countries. Dissemination practices and innovative methods are suggested. Recommendations for the future also include steps for the development and growth of FE in institutions and settings outside the school environment, thus spreading FE concepts and the resultant new ways of thinking and practices throughout the community.
Improving the Expansion of Electricity Services Considering Affordability Issues: A Case Study in Brazilian Low-Income Households
Authors: Piai Paiva Juliani Chico , Cordeiro Sandra Maria Almeida , Saath Kleverton Clóvis de Oliveira , Jannuzzi Gilberto de Martino
Published: August 2024

The assurance of universal access to electricity refers to not only physical access to electricity, heating, and/or cooling services but also making them affordable to families. This is the case in Brazil, where physical electricity access reaches more than 99% of the urban population, but a high proportion of households are disconnected due to lack of payment. Affordability is a key factor in planning the expansion and maintenance of the electricity grid. In this paper, therefore, we propose the development of a strategy, called the Payment Capability Indicator (PCI), that provides new information about the relationship between energy cost and family income. The classic indicator, the Ten Percent Rule (TPR), was the base, and empirical research was conducted in two low-income neighborhoods in Paraná state, southern Brazil. The results consider variables that add new information to guide local public policies, combining interventions to improve affordability, energy efficiency, alternatives to energy services and consumer behavioral changes.
Short-Term Forecasts of Energy Generation in a Solar Power Plant Using Various Machine Learning Models, along with Ensemble and Hybrid Methods
Authors: Piotrowski Paweł , Kopyt Marcin
Published: August 2024

High-quality short-term forecasts of electrical energy generation in solar power plants are crucial in the dynamically developing sector of renewable power generation. This article addresses the issue of selecting appropriate (preferred) methods for forecasting energy generation from a solar power plant within a 15 min time horizon. The effectiveness of various machine learning methods was verified. Additionally, the effectiveness of proprietary ensemble and hybrid methods was proposed and examined. The research also aimed to determine the appropriate sets of input variables for the predictive models. To enhance the performance of the predictive models, proprietary additional input variables (feature engineering) were constructed. The significance of individual input variables was examined depending on the predictive model used. This article concludes with findings and recommendations regarding the preferred predictive methods.
Dual Active Bridge Converter with Interleaved and Parallel Operation for Electric Vehicle Charging
Authors: Muhammetoglu Burak , Jamil Mohsin
Published: August 2024

This paper presents the design and optimization of a bidirectional Dual Active Bridge (DAB) converter for electric vehicle battery charging applications, encompassing both heavy and light electric vehicles. The core of this study is a 5.6 kW DAB converter that can seamlessly transition between 3.7 kW and 11.2 kW power outputs to accommodate different vehicle requirements without the need for circuit component changes. This flexibility is achieved through the novel integration of interleaved and parallel operation capabilities, allowing for efficient operation across a broad power range. Key innovations include the design of a high-frequency transformer with dual secondary outputs to facilitate power transfer at high currents up to 30 A, an optimized thermal design, and minimized stress on the circuit board. The use of next-generation power semiconductors and low-loss magnetic circuit elements has resulted in an optimized single-stage bidirectional converter design that showcases enhanced efficiency and competitiveness in the field. Furthermore, the converter’s design enables easy reconfiguration to meet the desired power output, vehicle type, and application needs, making it adaptable for future applications such as Vehicle-to-Grid (V2G) systems. The combination of these features—versatility in power output, efficient high-current transfer, innovative use of power semiconductors, and adaptability for future technologies—positions this DAB converter as a significant advancement in electric vehicle charging technology, offering a scalable solution to meet the evolving demands of electric mobility and renewable energy integration.
Characterization of Architecture Bounding Surfaces in Fluvial Tight Sandstone Reservoirs and Their Influence on Remaining Gas: A Case Study from the Suzhong Block, Sulige Gas Field
Authors: Liu Xinqiang , Li Jinbu , Liu Yuming , Chen Qi , Bai Yuqi , Li Fuping , Jin Lei , Zhang Bingbing
Published: August 2024

The H8 and S1 reservoirs in the lower Shihezi Formation and Shanxi Formation of the central block in the Sulige Gas Field are typical fluvial tight sandstone reservoirs. Due to frequent river channel migrations during deposition, the reservoirs exhibit complex spatial structures with developed intra-sand mudstone interlayers. As the field has entered the middle and late stages of development, the distribution of remaining gas is intricately controlled by these interlayers, necessitating research on their distribution to understand the remaining gas patterns and types for effective extraction enhancement. However, the thinness of interlayers presents a challenge for precise prediction. Addressing this, this study delineates different interlayer types and their origins, applies reservoir architecture theory, and utilizes bounding surfaces characterization, planar and sectional distribution studies, unit scale analysis, horizontal well data, and quantitative characterization methods to investigate the internal reservoir architecture bounding surfaces. The study finely portrays the interlayer distribution, analyzes the control of reservoir architecture bounding surfaces on remaining gas, and establishes a multi-tiered reservoir architecture model in the study area. Numerical simulation of the gas reservoir clarifies the types of remaining gas enrichment. This study also identifies and quantitatively characterizes the 5–3 level architecture bounding surfaces within the sandbody, categorizing the remaining gas into bounding surfaces-controlled, well-network uncontrolled, and single-layer unperforated types, proposing targeted enhancement measures for each type. Based on the findings, four vertical wells and three horizontal wells were deployed, improving the well network density to three wells per square kilometer. The first completed horizontal well encountered an effective drilling rate of 61.7%, marking significant implications for the exploitation and recovery enhancement of similar tight sandstone gas reservoirs.
The Impact of Primary Literature-Based, Critical Thinking Activities on Competency Enhancement for Pre-Health Students
Authors: Katzman Shoshana D. , Carrion Carmen A. , Hurst-Kennedy Jennifer
Published: August 2024

Thinking and reasoning competencies are crucial for the success of future healthcare professionals and are noted as pre-professional competencies for medical school admissions. At Agnes Scott College, our graduate-level Medical Cell Biology class focuses on cellular structure and function in human disease. In this course, students complete assignments meant to foster critical thinking competencies, wherein they analyze primary articles on the cellular pathogenesis of disease and relevant drug therapies. To assess student perspectives on these assignments, we developed a survey to gauge student attitudes toward the effectiveness of these assignments in supporting their learning and preparing them as applicants to various health professions programs. Attitudinal data shows that these assignments have helped students think critically when evaluating scientific literature and bolstered their understanding of cell biology in the progression and treatment of human pathologies, better preparing them for their future careers in the health professions.
Genome-Wide Characterization of the BTB Gene Family in Poplar and Expression Analysis in Response to Hormones and Biotic/Abiotic Stresses
Authors: Yue Jing , Dai Xinren , Li Quanzi , Wei Mingke
Published: August 2024

The BTB (Broad-complex, tramtrack, and bric-a-brac) gene family, characterized by a highly conserved BTB domain, is implicated in a spectrum of biological processes, encompassing growth and development, as well as stress responses. Characterization and functional studies of BTB genes in poplar are still limited, especially regarding their response to hormones and biotic/abiotic stresses. In this study, we conducted an HMMER search in conjunction with BLASTp and identified 95 BTB gene models in Populus trichocarpa. Through domain motif and phylogenetic relationship analyses, these proteins were classified into eight families, NPH3, TAZ, Ankyrin, only BTB, BACK, Armadillo, TPR, and MATH. Collinearity analysis of poplar BTB genes with homologs in six other species elucidated evolutionary relationships and functional conservations. RNA-seq analysis of five tissues of poplar identified BTB genes as playing a pivotal role during developmental processes. Comprehensive RT-qPCR analysis of 11 BTB genes across leaves, roots, and xylem tissues revealed their responsive expression patterns under diverse hormonal and biotic/abiotic stress conditions, with varying degrees of regulation observed in the results. This study marks the first in-depth exploration of the BTB gene family in poplar, providing insights into the potential roles of BTB genes in hormonal regulation and response to stress.
Advances in Molecular Mechanisms of Kidney Disease: Integrating Renal Tumorigenesis of Hereditary Cancer Syndrome
Authors: Cicchetti Rossella , Basconi Martina , Litterio Giulio , Mascitti Marco , Tamborino Flavia , Orsini Angelo , Digiacomo Alessio , Ferro Matteo , Schips Luigi , Marchioni Michele
Published: August 2024

Renal cell carcinoma (RCC) comprises various histologically distinct subtypes, each characterized by specific genetic alterations, necessitating individualized management and treatment strategies for each subtype. An exhaustive search of the PubMed database was conducted without any filters or restrictions. Inclusion criteria encompassed original English articles focusing on molecular mechanisms of kidney cancer. On the other hand, all non-original articles and articles published in any language other than English were excluded. Hereditary kidney cancer represents 5–8% of all kidney cancer cases and is associated with syndromes such as von Hippel–Lindau syndrome, Birt–Hogg–Dubè syndrome, succinate dehydrogenase-deficient renal cell cancer syndrome, tuberous sclerosis complex, hereditary papillary renal cell carcinoma, fumarate hydratase deficiency syndrome, BAP1 tumor predisposition syndrome, and other uncommon hereditary cancer syndromes. These conditions are characterized by distinct genetic mutations and related extra-renal symptoms. The majority of renal cell carcinoma predispositions stem from loss-of-function mutations in tumor suppressor genes. These mutations promote malignant advancement through the somatic inactivation of the remaining allele. This review aims to elucidate the main molecular mechanisms underlying the pathophysiology of major syndromes associated with renal cell carcinoma. By providing a comprehensive overview, it aims to facilitate early diagnosis and to highlight the principal therapeutic options available.
Ciliary Motility Decreased by a CO2/HCO3−-Free Solution in Ciliated Human Nasal Epithelial Cells Having a pH Elevated by Carbonic Anhydrase IV
Authors: Okamoto Shota , Yasuda Makoto , Kawaguchi Kotoku , Yasuoka Kasane , Kikukawa Yumi , Asano Shinji , Tsujii Taisei , Inoue Sana , Amagase Kikuko , Inui Taka-aki , Hirano Shigeru , Inui Toshio , Marunaka Yoshinori , Nakahari Takashi
Published: August 2024

An application of CO2/HCO3−-free solution (Zero-CO2) did not increase intracellular pH (pHi) in ciliated human nasal epithelial cells (c-hNECs), leading to no increase in frequency (CBF) or amplitude (CBA) of the ciliary beating. This study demonstrated that the pHi of c-hNECs expressing carbonic anhydrase IV (CAIV) is high (7.64), while the pHi of ciliated human bronchial epithelial cells (c-hBECs) expressing no CAIV is low (7.10). An extremely high pHi of c-hNECs caused pHi, CBF and CBA to decrease upon Zero-CO2 application, while a low pHi of c-hBECs caused them to increase. An extremely high pHi was generated by a high rate of HCO3− influx via interactions between CAIV and Na+/HCO3− cotransport (NBC) in c-hNECs. An NBC inhibitor (S0859) decreased pHi, CBF and CBA and increased CBF and CBA in c-hNECs upon Zero-CO2 application. In conclusion, the interactions of CAIV and NBC maximize HCO3− influx to increase pHi in c-hNECs. This novel mechanism causes pHi to decrease, leading to no increase in CBF and CBA in c-hNECs upon Zero-CO2 application, and appears to play a crucial role in maintaining pHi, CBF and CBA in c-hNECs periodically exposed to air (0.04% CO2) with respiration.
Functional Peptides from Yak Milk Casein: Biological Activities and Structural Characteristics
Authors: Wang Wen , Liang Qi , Zhao Baotang , Chen Xuhui , Song Xuemei
Published: August 2024

The average content of casein in yak milk is 40.2 g/L. Casein can be degraded by enzymatic digestion or food processing to produce abundant degradation peptides. International researchers have studied the degradation peptides of yak milk casein by using multiple techniques and methods, such as in vitro activity tests, cellular experiments, proteomics, bioinformatics, etc., and found that the degradation peptides have a wide range of functional activities that are beneficial to the human body, such as angiotensin-converting enzyme (ACE) inhibitory, antioxidant, anti-inflammatory, antidiabetic, antimicrobial, anticancer, and immunomodulatory activities, etc., and it has been proved that the types and strengths of functional activities are closely related to the structural characteristics of the peptides. This paper describes the characteristics of yak milk proteins, the functional activities, and mechanism of action of degraded peptides. Based on the types of functional activities of yak milk casein degradation peptides, we classified and elucidated the effects of structural factors, such as peptide molecular weight, peptide length, amino acid sequence, physicochemical properties, electrical charge, hydrophobicity, spatial conformation, chain length, and the type of enzyme on these activities. It reveals the great potential of yak milk casein degradation peptides as functional active peptide resources and as auxiliary treatments for diseases. It also provides important insights for analyzing yak casein degradation peptide activity and exploring high-value utilization.
Transglutaminase 2 Regulates HSF1 Gene Expression in the Acute Phase of Fish Optic Nerve Regeneration
Authors: Sugitani Kayo , Mokuya Takumi , Kanai Yu , Takaya Yurina , Omori Yuya , Koriyama Yoshiki
Published: August 2024

Fish retinal ganglion cells (RGCs) can regenerate after optic nerve lesions (ONLs). We previously reported that heat shock factor 1 (HSF1) and Yamanaka factors increased in the zebrafish retina 0.5–24 h after ONLs, and they led to cell survival and the transformation of neuro-stem cells. We also showed that retinoic acid (RA) signaling and transglutaminase 2 (TG2) were activated in the fish retina, performing neurite outgrowth 5–30 days after ONLs. In this study, we found that RA signaling and TG2 increased within 0.5 h in the zebrafish retina after ONLs. We examined their interaction with the TG2-specific morpholino and inhibitor due to the significantly close initiation time of TG2 and HSF1. The inhibition of TG2 led to the complete suppression of HSF1 expression. Furthermore, the results of a ChIP assay with an anti-TG2 antibody evidenced significant anti-TG2 immunoprecipitation of HSF1 genome DNA after ONLs. The inhibition of TG2 also suppressed Yamanaka factors’ gene expression. This rapid increase in TG2 expression occurred 30 min after the ONLs, and RA signaling occurred 15 min before this change. The present study demonstrates that TG2 regulates Yamanaka factors via HSF1 signals in the acute phase of fish optic nerve regeneration.
Monitoring Fruit Growth and Development in Apricot (Prunus armeniaca L.) through Gene Expression Analysis
Authors: Ortuño-Hernández Germán , Sánchez María , Ruiz David , Martínez-Gómez Pedro , Salazar Juan Alfonso
Published: August 2024

The main objective of this study was to monitor apricot development and ripening through gene expression analysis of key candidate genes using the RT-qPCR technique. Eight apricot cultivars were selected to analyze phenological and genetic patterns from pre-ripening stages through to postharvest. In addition, 19 selected genes were analyzed in the contrasting cultivars ‘Cebas Red’ and ‘Rojo Pasión’ in different stages (two preharvest stages S1 and S2, one harvest stage S3, and two postharvest stages S4 and S5). This pool of genes included genes related to fruit growth and ripening, genes associated with fruit color, and genes linked to the fruit’s nutraceutical aspects. Among the studied genes, Polygalacturonase (PG), Pectin methylesterase (PME), Aminocyclopropane-1-carboxylate synthase (ACS), and Myo-inositol-1-phosphate synthase (INO1) were directly related to fruit maturation and quality. Significant differential expression was observed between the cultivars, which correlated with variations in firmness, shelf life, and sensory characteristics of the apricots. ‘Rojo Pasión’ displayed high levels of PG, associated with rapid maturation and shorter postharvest shelf life, whereas ‘Cebas Red’ exhibited lower levels of this gene, resulting in greater firmness and extended shelf life. Genes CCD4, CRTZ, and ZDS, related to carotenoids, showed varied expression patterns during growth and postharvest stages, with higher levels in ‘Rojo Pasión’. On the other hand, Sucrose synthase (SUSY) and Lipoxygenase (LOX2) were prominent during the postharvest and growth stages, respectively. Additionally, GDP-L-galactose phosphorylase (VTC2_5) was linked to better postharvest performance. This research provides valuable insights for future breeding initiatives aimed at enhancing the quality and sustainability of apricot cultivation.
CRISPR/Cas-Mediated Knockdown of PD-L1 and KRAS in Lung Cancer Cells
Authors: Abounar Summer A. , El-Nikhely Nefertiti A. , Turkowski Kati , Savai Rajkumar , Saeed Hesham
Published: August 2024

Cancer cells can escape death and surveillance by the host immune system in various ways. Programmed cell death ligand 1 (PD-L1) is a transmembrane protein that is expressed by most cell types, including cancer cells, and can provide an inhibitory signal to its receptor PD-1, which is expressed on the surface of activated T cells, impairing the immune response. PD-L1/PD-1-mediated immune evasion is observed in several KRAS-mutated cancers. In the current study, we used the CRISPR/Cas9 system to knock down PD-L1 and KRAS in adenocarcinoma lung cells (A549 and H1975). Knockdown of PD-L1 was validated by qPCR and coculture with lymphocytes. The cells were functionally analyzed for cell cycle, migration and apoptosis. In addition, the effects of PD-L1 and KRAS downregulation on chemotherapy sensitivity and expression of inflammatory markers were investigated. Suppression of PD-L1 and KRAS led to a slowdown of the cell cycle in the G0/G1 phase and reduced migration, increased sensitivity to chemotherapy and triggered apoptosis of cancer cells. In addition, the conditioned medium of the modulated cells significantly affected the native cancer cells and reduced their viability and drug resistance. Our study suggests that dual silencing of PD-L1 and KRAS by CRISPR/Cas9 may be a promising therapeutic approach for the treatment of lung cancer.
EPA and DHA Enhance CACT Promoter Activity by GABP/NRF2
Authors: Stanca Eleonora , Spedicato Francesco , Giudetti Anna Maria , Giannotti Laura , Di Chiara Stanca Benedetta , Damiano Fabrizio , Siculella Luisa
Published: August 2024

Carnitine-acylcarnitine translocase (CACT) is a nuclear-encoded mitochondrial carrier that catalyzes the transfer of long-chain fatty acids across the inner mitochondrial membrane for β-oxidation. In this study, we conducted a structural and functional characterization of the CACT promoter to investigate the molecular mechanism underlying the transcriptional regulation of the CACT gene by n-3 PUFA, EPA and DHA. In hepatic BRL3A cells, EPA and DHA stimulate CACT mRNA and protein expression. Deletion promoter analysis using a luciferase reporter gene assay identified a n-3 PUFA response region extending from −202 to −29 bp. This region did not contain a response element for PPARα, a well-known PUFA-responsive nuclear receptor. Instead, bioinformatic analysis revealed two highly conserved GABP responsive elements within this region. Overexpression of GABPα and GABPβ subunits, but not PPARα, increased CACT promoter activity, more remarkably upon treatment with EPA and DHA. ChIP assays showed that n3-PUFA enhanced the binding of GABPα to the −202/−29 bp sequence. Furthermore, both EPA and DHA induced nuclear accumulation of GABPα. In conclusion, our findings indicate that the upregulation of CACT by n3-PUFA in hepatic cells is independent from PPARα and could be mediated by GABP activation.
A Narrative Review: Immunometabolic Interactions of Host–Gut Microbiota and Botanical Active Ingredients in Gastrointestinal Cancers
Authors: Li Shanlan , Feng Wuwen , Wu Jiaqi , Cui Herong , Wang Yiting , Liang Tianzhen , An Jin , Chen Wanling , Guo Zhuoqian , Lei Haimin
Published: August 2024

The gastrointestinal tract is where the majority of gut microbiota settles; therefore, the composition of the gut microbiota and the changes in metabolites, as well as their modulatory effects on the immune system, have a very important impact on the development of gastrointestinal diseases. The purpose of this article was to review the role of the gut microbiota in the host environment and immunometabolic system and to summarize the beneficial effects of botanical active ingredients on gastrointestinal cancer, so as to provide prospective insights for the prevention and treatment of gastrointestinal diseases. A literature search was performed on the PubMed database with the keywords “gastrointestinal cancer”, “gut microbiota”, “immunometabolism”, “SCFAs”, “bile acids”, “polyamines”, “tryptophan”, “bacteriocins”, “immune cells”, “energy metabolism”, “polyphenols”, “polysaccharides”, “alkaloids”, and “triterpenes”. The changes in the composition of the gut microbiota influenced gastrointestinal disorders, whereas their metabolites, such as SCFAs, bacteriocins, and botanical metabolites, could impede gastrointestinal cancers and polyamine-, tryptophan-, and bile acid-induced carcinogenic mechanisms. GPRCs, HDACs, FXRs, and AHRs were important receptor signals for the gut microbial metabolites in influencing the development of gastrointestinal cancer. Botanical active ingredients exerted positive effects on gastrointestinal cancer by influencing the composition of gut microbes and modulating immune metabolism. Gastrointestinal cancer could be ameliorated by altering the gut microbial environment, administering botanical active ingredients for treatment, and stimulating or blocking the immune metabolism signaling molecules. Despite extensive and growing research on the microbiota, it appeared to represent more of an indicator of the gut health status associated with adequate fiber intake than an autonomous causative factor in the prevention of gastrointestinal diseases. This study detailed the pathogenesis of gastrointestinal cancers and the botanical active ingredients used for their treatment in the hope of providing inspiration for research into simpler, safer, and more effective treatment pathways or therapeutic agents in the field.
Comprehensive Analysis of Methylome and Transcriptome to Identify Potential Genes Regulating Porcine Testis Development
Authors: Feng Yue , Zhang Yu , Wu Junjing , Qiao Mu , Zhou Jiawei , Xu Zhong , Li Zipeng , Sun Hua , Peng Xianwen , Mei Shuqi
Published: August 2024

DNA methylation plays a critical role in regulating gene expression during testicular development. However, few studies report on candidate genes related to the DNA methylation regulation of porcine testicular development. This study examined the differentially expressed genes (DEGs) and their methylation levels in testicular tissues from pigs at 60 days of age (60 d) and 180 days of age (180 d) using RNA-Seq and whole genome bisulfite sequencing (WGBS). It was determined that DNA methylation primarily occurs in the cytosine–guanine (CG) context, and the analysis identified 106,282 differentially methylated regions (DMRs) corresponding to 12,385 differentially methylated genes (DMGs). Further integrated analysis of RNA-Seq and WGBS data revealed 1083 DMGs negatively correlated with the expression of DEGs. GO analysis showed that these genes were significantly enriched in spermatogenesis, germ cell development, and spermatid differentiation. The screening of enriched genes revealed that hyper-methylation repressed ADAM30, ADAM3A, DPY19L2, H2BC1, MAK, RPL10L, SPATA16, and YBX2, while hypo-methylation elevated CACNA1I, CADM1, CTNNB1, JAM2, and PAFAH1B3 expression. Additionally, the methylation status of the key genes ADAM3A, ADAM30, YBX2, JAM2, PAFAH1B3, and CTNNB1 was detected by bisulfite sequencing PCR (BSP). This study offers insights into the epigenetic regulation mechanisms underlying porcine testicular development.
Deciphering the Impact of Nucleosides and Nucleotides on Copper Ion and Dopamine Coordination Dynamics
Authors: Sadowska Patrycja , Jankowski Wojciech , Bregier-Jarzębowska Romualda , Pietrzyk Piotr , Jastrząb Renata
Published: August 2024

The mode of coordination of copper(II) ions with dopamine (DA, L) in the binary, as well as ternary systems with Ado, AMP, ADP, and ATP (L′) as second ligands, was studied with the use of experimental—potentiometric and spectroscopic (VIS, EPR, NMR, IR)—methods and computational—molecular modeling and DFT—studies. In the Cu(II)/DA system, depending on the pH value, the active centers of the ligand involved in the coordination with copper(II) ions changed from nitrogen and oxygen atoms (CuH(DA)3+, Cu(DA)2+), via nitrogen atoms (CuH2(DA)24+), to oxygen atoms at strongly alkaline pH (Cu(DA)22+). The introduction of L′ into this system changed the mode of interaction of dopamine from oxygen atoms to the nitrogen atom in the hydroxocomplexes formed at high pH values. In the ternary systems, the ML′-L (non-covalent interaction) and ML′HxL, ML′L, and ML′L(OH)x species were found. In the Cu(II)/DA/AMP or ATP systems, mixed forms were formed up to a pH of around 9.0; above this pH, only Cu(II)/DA complexes occurred. In contrast to systems with AMP and ATP, ternary species with Ado and ADP occurred in the whole pH range at a high concentration, and moreover, binary complexes of Cu(II) ions with dopamine did not form in the detectable concentration.
Mutation Spectrum of GAA Gene in Pompe Disease: Current Knowledge and Results of an Italian Study
Authors: Moschetti Marta , Lo Curto Alessia , Giacomarra Miriam , Francofonte Daniele , Zizzo Carmela , Messina Elisa , Duro Giovanni , Colomba Paolo
Published: August 2024

Studying a patient with Pompe disease (PD) is like opening Pandora’s box. The specialist is faced with numerous clinical features similar to those of several diseases, and very often the symptoms are well hidden and none is associated with this rare disease. In recent years, scientific interest in this disease has been growing more and more, but still no symptom is recognized as key to a correct diagnosis of it, nor is there any specific disease marker to date. New diagnostic/therapeutic proposals on disease allow for the diffusion of knowledge of this pathology for timely diagnosis of the patient. Due to unawareness and difficulty in diagnosis, many adults with PD are diagnosed with great delay. In this article, we report and discuss current knowledge of PD and provide new data from work conducted on a cohort of 2934 Italian subjects recruited in recent years. A genetic analysis of the GAA gene was performed on patients with significant clinical signs and pathological enzyme activity to define the genetic profile of subjects. This identified 39 symptomatic PD subjects with low acid alpha-glucosidase enzyme activity and the presence of two causative mutations in GAA gene regions. Furthermore, 22 subjects with genetic variants of uncertain significance (GVUS) were identified.
Treatment of Chronic Haemophilic Synovitis with PRP: Clinical and In Vitro Studies
Authors: Caviglia Horacio , Landro María Eulalia , Oneto Paula , Cambiaggi Guillermo , Galatro Gustavo , Berni Micaela , Caliogna Laura , Carrera Silva Eugenio Antonio , Pasta Gianluigi
Published: August 2024

Intra-articular blood, iron and hemosiderin, hydroxyl radical cytokines, and neo-angiogenesis cause synovial inflammation, which leads to cartilage and joint damage. Platelet-rich plasma (PRP) inhibits most of the mediators that produce and maintain synovitis. We compile here our work showing the clinical effectiveness of intra-articular PRP injections and their potential role in stopping articular cartilage damage due to bleeding and its possible repair. A total of 116 joints, including knees (63%), elbows (19.8%), and ankles (17.2%), were treated with intra-articular injections of PRP. Moreover, we also show here the number of extracellular DNA traps (ETs) and the PRP effect in the synovial fluid of patients at the time of treatment and six months after. Clinically, it is demonstrated that PRP is effective in reducing bleeding episodes (p < 0.001) and pain (p < 0.0001) and improving the hemophilia joint health score (HJHS) (p < 0.001) at one year of follow-up. Furthermore, our results demonstrate that PRP inhibits ET formation in vitro and reconstitutes the immune system’s cellular components in the synovial fluid of patients after treatment. We conclude that PRP can be considered an effective, safe, and easy treatment for hemophilic synovitis.
Differences in Bone Metabolism between Children with Prader–Willi Syndrome during Growth Hormone Treatment and Healthy Subjects: A Pilot Study
Authors: Gajewska Joanna , Chełchowska Magdalena , Szamotulska Katarzyna , Klemarczyk Witold , Strucińska Małgorzata , Ambroszkiewicz Jadwiga
Published: August 2024

Despite therapy with growth hormone (GH) in children with Prader–Willi syndrome (PWS), low bone mineral density and various orthopedic deformities have been observed often. Therefore, this study aimed to analyze bone markers, with an emphasis on vitamin K-dependent proteins (VKDPs), in normal-weight children with PWS undergoing GH therapy and a low-energy dietary intervention. Twenty-four children with PWS and 30 healthy children of the same age were included. Serum concentrations of bone alkaline phosphatase (BALP), osteocalcin (OC), carboxylated-OC (Gla-OC), undercarboxylated-OC (Glu-OC), periostin, osteopontin, osteoprotegerin (OPG), sclerostin, C-terminal telopeptide of type I collagen (CTX-I), and insulin-like growth factor-I (IGF-I) were determined using immunoenzymatic methods. OC levels and the OC/CTX-I ratios were lower in children with PWS than in healthy children (p = 0.011, p = 0.006, respectively). Glu-OC concentrations were lower (p = 0.002), but Gla-OC and periostin concentrations were higher in patients with PWS compared with the controls (p = 0.005, p < 0.001, respectively). The relationships between IGF-I and OC (p = 0.013), Gla-OC (p = 0.042), and the OC/CTX-I ratio (p = 0.017) were significant after adjusting for age in children with PWS. Bone turnover disorders in children with PWS may result from impaired bone formation due to the lower concentrations of OC and the OC/CTX-I ratio. The altered profile of OC forms with elevated periostin concentrations may indicate more intensive carboxylation processes of VKDPs in these patients. The detailed relationships between the GH/IGF-I axis and bone metabolism markers, particularly VKDPs, in children with PWS requires further research.