bluuebunny/crossref_metadata_2025 huggingface dataset:
When brands show a human side, hearts open a wide! Enhancing prosocial behavior through anthropomorphized brand messaging in cause related marketing
Authors: Durgha Devi L. , Arumugam Thangaraja
Published: December 2024

This paper discusses the influence mechanism of prosocial behavior through anthropomorphized brand messaging in cause related marketing among young adults, based on heuristic systematic model, the study assesses how different modes of information processing shapes consumers’ prosocial behavior, with moderating effect of execution style. An online survey was conducted among 299 young adults in Chennai, Tamil Nadu, India, utilizing a purposive sampling technique. Structural Equation Modeling was applied using Smart-PLS. The findings indicate that anthropomorphized brand message in cause related marketing significantly influence prosocial behavior. Systematic information processing is positively associated with brand anthropomorphism, while heuristic processing shows a negative association. The execution style moderates the relationship between brand anthropomorphism and prosocial behavior, with cause-focused messaging enhancing the effectiveness of anthropomorphism in cause related marketing initiatives. The study suggests that brands can enhance effectiveness of cause related marketing by adopting anthropomorphized messaging, which fosters deeper emotional connectionsand encourages systematic information processing. The implications are significant for marketers aiming to design effective cause related marketing strategies that resonate with socially conscious young adults.
VET leaders’ collaborative problem-solving skills: insights from a professionals’ master’s degree program
Authors: Trikoili Anna , Georgiou Despoina , Pittich Daniel
Published: December 2024

Vocational education and training (VET) structures are ecosystems bound to collaboration. As VET leaders’ roles become increasingly diverse and demanding, challenges must be addressed through collaborative efforts within teams. Leaders’ collaborative problem-solving (CPS) skills remain unexplored despite the importance of CPS in VET settings. This single case study investigates the CPS skills that VET leaders use in addressing tasks and challenges in an educational setting. Postgraduate students in a professional master’s degree program with several years of work experience in VET leadership positions served as study participants. We utilised content analysis on video data of participants engaging in group work on an assignment that required them to give both constructed responses and creative solutions. The study also analysed VET leaders’ self-reflections on their CPS skills collected through a survey tool. Our results revealed that despite participants’ similar professional profiles, their performance in CPS varied significantly. Older participants seemed to have better self-reflection skills, and experienced professionals could allocate cognitive resources to more complex strategic and meta-cognitive processes. This study can be used as a roadmap for targeted professional development programs aiming to improve CPS skills and for informed decisionmaking in choosing professionals for pivotal leadership positions.
English learners with dyslexia benefit from English dyslexia intervention: an observational study of routine intervention practices
Authors: Middleton Anna E. , Davila Marcela , Frierson Sheryl L.
Published: December 2024

Introduction

Learning to read when the language of the curriculum differs from one’s home language can pose unique challenges. For example, compared to the language spoken at home, the learner may be less familiar with the sound structure and have relatively limited word knowledge in the language of instruction. In the United States, English is the primary language of reading instruction for students who are English Proficient (EP) and for English Learners (EL). Current evidence indicates that for both EP and EL students, code-based competencies and meaning-based skills are important for learning to read. English-language reading interventions have been shown to be beneficial for EPs and ELs with reading problems, though it is not clear if this is also true when the reading problem is a reading disorder like dyslexia.

Methods

The current study addresses this question by comparing EL and EP student’s reading profile at baseline and changes over time in response to evidence-based English Language Dyslexia Instruction (ELDI) in public schools. One-hundred eighty-six students with dyslexia were followed over the course of two academic years. Assessments measured code and meaning-based reading skills. Multivariate profile analysis and linear mixed effects modeling were conducted to compare baseline reading profiles as well as growth in targeted skills over time.

Results

Findings reveal similar patterns of reading profiles across EL and EP groups, with more severe baseline deficits emerging for ELs. Groups performed equivalently on target reading skills after two years of intensive multi-componential reading intervention.

Conclusion

Findings confirm and extend previous research, suggesting ELs with Dyslexia can be identified and successfully served through routine practices, including ELDI.
Rubric development and validation for assessing educational robotics skills
Authors: Yousef Ahmad , Ayyoub Abedalkarim
Published: December 2024

The current study describes the process of development and validation of a rubric for assessing educational robotics skills among middle school students. A multiphase method has been followed, including a literature study, expert consultation, content validation, pilot testing, reliability analysis, and construct validation. The resulting dual-category rubric designing and programming skills were further elaborated by specific criteria and performance levels. Content validation identified seven key criteria: stability and durability, motors, innovation, code organization, dependability and reliability, movement and rotation, and innovative use of sensors. The results of inter-rater reliability analysis for all criteria indicated good agreement, with Krippendorff’s alpha ranging from 0.941 to 1.000. Additionally, construct validation using exploratory factor analysis confirmed a two-factor structure that aligns with the intended domains of design and programming skills, explaining 67.4% of the total variance. The rubric was consistent with learning/teaching theories such as Bloom’s taxonomy, constructivist learning theory, and self-determination theory. This rubric fulfills the existing need for a specific assessment tool in educational robotics and supports educational practices through very detailed feedback to students on their performance. This adds much to educational assessment and education in robotics and enhances teaching and learning outcomes for STEAM education in various settings.
Interaction between Vitamin D homeostasis, gut microbiota, and central precocious puberty
Authors: Guo Doudou , Ning Xin , Bai Tao , Tan Lingfang , Zhou Yanfen , Guo Zhichen , Li Xin
Published: December 2024

Central precocious puberty (CPP) is an endocrine disease in children, characterized by rapid genital development and secondary sexual characteristics before the age of eight in girls and nine in boys. The premature activation of the hypothalamic-pituitary-gonadal axis (HPGA) limits the height of patients in adulthood and is associated with a higher risk of breast cancer. How to prevent and improve the prognosis of CPP is an important problem. Vitamin D receptor (VDR) is widely expressed in the reproductive system, participates in the synthesis and function of regulatory sex hormones, and affects the development and function of gonads. In addition, gut microbiota plays an important role in human health by mainly regulating metabolites, energy homeostasis, and hormone regulation. This review aims to clarify the effect of vitamin D deficiency on the occurrence and development of CPP and explore the role of gut microbiota in it. Although evidence on the interaction between vitamin D deficiency, gut microbiota, and sexual development remains limited, vitamin D supplementation and gut microbiota interventions offer a promising, non-invasive strategy for managing CPP.
L-shaped relationship between atherogenic index of plasma with uric acid levels and hyperuricemia risk
Authors: Huang Jingjing , Chen Chunhong , Jie Chunxiao , Li Ruying , Chen Chunyong
Published: December 2024

Background

Hyperuricemia is a major risk factor for cardiovascular disease. This study aimed to investigate the relationship between the atherogenic index of plasma (AIP) and serum uric acid (SUA) levels, as well as the risk of hyperuricemia.

Methods

Utilizing data from the National Health and Nutrition Examination Survey (NHANES), we conducted a cross-sectional study involving 9,439 participants aged 18 years and above with complete triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) data. AIP was calculated as the logarithm of the ratio of TG to HDL-C. Weighted linear regression, weighted logistic regression, subgroup analysis, generalized additive model, restricted cubic spline and two-part linear and logistic regression were utilized to examine the relationships between AIP and SUA levels and hyperuricemia risk.

Results

We identified a non-linear and L-shaped relationship between AIP and both SUA levels and hyperuricemia prevalence, with significant increasing observed up to a saturation point (0.588 for uric acid levels and 0.573 for hyperuricemia prevalence). Below these thresholds, the odds ratios (OR) for increased SUA and hyperuricemia were 0.854 (95% confidence interval [CI]: 0.762, 0.946) and 4.4 (95% CI: 3.528, 5.488), respectively (P<0.001). Beyond these points, the associations were not statistically significant.

Conclusion

Our findings suggest that AIP is significantly and non-linear associated with SUA levels and hyperuricemia risk, with a saturation effect observed beyond specific thresholds. These insights could inform clinical strategies for managing cardiovascular and metabolic risks associated with elevated AIP. Further longitudinal studies are warranted to confirm these associations and elucidate the underlying mechanisms.
Associations of systemic inflammation and systemic immune inflammation with serum uric acid concentration and hyperuricemia risk: the mediating effect of body mass index
Authors: Zhang Yueyue , Han Shichao , Duan Zhizhou , Tian Xu , Li Xueyi , Hou Guangdong , Gao Xuelin , Tian Chunjuan , Li Xiangyu , Yu Wenyuan , Zhou Qin , Niu Zhiping , Wang Fuli
Published: December 2024

Background

With the development of lifestyle, elevated uric acid and hyperuricemia have become important factors affecting human health, but the biological mechanism and risk factors are still unclear.

Methods

A multi-stage, cross-sectional study of 41,136 adults from the NHANES 2003-2018 was conducted. Serum uric acid concentrations, platelet, neutrophil, lymphocyte, and monocyte counts were measured. The systemic inflammation response (SIRI) index and systemic immune-inflammatory (SII) index were calculated to reflect systemic inflammation and systemic immune inflammation. The height and weight data were obtained to assess body mass index (BMI). Generalized linear models were used to examine the relationships of SIRI and SII with uric acid and hyperuricemia risk, as well as the associations of SIRI and SII with BMI, and BMI with uric acid and hyperuricemia risk. Causal mediation effect model was used to assess the mediating effect of BMI in the relationships of SIRI, and SII with uric acid concentration and hyperuricemia risk.

Results

The prevalence of hyperuricemia in US adults is 19.78%. Positive associations were found in the relationships of SIRI and SII with uric acid level, hyperuricemia risk, and BMI, as well as the relationships of BMI with uric acid and hyperuricemia risk. Causal mediation effect model showed that BMI played an important mediating role in the relationships of SIRI, and SII with uric acid concentration and hyperuricemia risk, with the proportion of mediating effect ranging from 23.0% to 35.9%.

Conclusion

Exposure to higher SIRI and SII is associated with increased uric acid concentration and hyperuricemia risk in adults, and BMI plays an important mediating effect. Reducing systemic inflammation and systemic immune inflammation and proper weight control could be effective ways to reduce hyperuricemia prevalence and related health problems.
Higher remnant cholesterol increases the risk of coronary heart disease and diabetes in postmenopausal women
Authors: Zhang Yan , Song Kexin , Bi Shuli , Li Mingyang , Yao Zhuhua
Published: December 2024

Background

Postmenopausal women represent the demographic increasingly susceptible to cardiovascular and metabolic diseases. Elevated levels of remnant cholesterol (RC) have been implicated in atherosclerosis and insulin resistance.

Methods

This study aimed to investigate the relationship between RC and the prevalence of coronary heart disease (CHD), diabetes, and CHD combined with diabetes in a nationally representative sample of US postmenopausal women using data from the National Health and Nutrition Examination Survey (NHANES) 2007-2018. Multivariate logistic regression models were employed to evaluate the association between RC and the outcomes of interest. Nonlinear associations were assessed using restricted cubic splines (RCS), and subgroup analyses, along with interaction tests, were performed.

Results

A total of 1611 participants were included in the final analysis. Higher RC levels were significantly associated with increased risks of CHD [OR=1.67, 95%CI (1.02, 2.74)], diabetes [OR=1.77, 95%CI (1.22, 2.58)], and CHD combined with diabetes [OR=2.28, 95%CI (1.17, 4.42)] (all P<0.05). Compared to the lowest RC quartile (Q1), the highest quartile (Q4) demonstrated elevated incidences of CHD [OR=1.76, 95%CI (1.04, 2.98)], diabetes [OR=1.81, 95%CI (1.30, 2.53)], and CHD combined with diabetes [OR=3.08, 95%CI (1.29, 7.37)] (all P<0.05). RCS curves indicated a nearly linear relationship between RC and the risks of CHD, diabetes, and CHD combined with diabetes.

Conclusion

Our study reveals a significant positive correlation between RC levels and the prevalence of CHD, diabetes, and CHD combined with diabetes among postmenopausal women. Understanding these associations could potentially inform targeted prevention and management strategies tailored to this vulnerable population.
Evaluation of thyroid function tests among children with neurological disorders
Authors: Meng Haojie , Bigambo Francis Manyori , Gu Wei , Wang Xu , Li Yang
Published: December 2024

Background

Thyroid hormones (THs) are essential for brain development. Numerous studies have identified significant links between thyroid dysfunction and cognitive function. However, research on the significance and necessity of thyroid function tests in diagnosis of neurological disorders is limited and subject to controversy.

Methods

Our study employed a combination of meta-analysis and case-control design. For the meta-analysis, we conducted a systematic search of online databases for studies that compared thyroid function tests in children with neurological disorders to controls. In our case-control study, we recruited a total of 11836 children, comprising 7035 cases and 4801 healthy controls. Wilcoxon Rank Sum Test was used to determine characteristics of thyroid function between the cases and healthy controls. In order to exclude the false discovery rate (FDR), the Benjamini-Hochberg (BH) procedure is applied.

Results

A total of 12 relevant literature sources were included in the meta-analysis. Compared with controls, free thyroxine (FT4) levels were significantly decreased in neurological disorders in meta-analysis (MD = -0.29, 95% CI: -0.50 to -0.09), whereas thyroid-stimulating hormone (TSH) levels showed no significant difference (MD = -0.07, 95% CI: -0.36 to 0.21). In our case-control study, levels of free thyroxine (FT4), total triiodothyronine (TT3), total thyroxine (TT4), and anti-thyroglobulin antibodies (TG-Ab) were notably reduced among individuals with neurological disorders, compared with healthy controls (P<0.001, P<0.001, P=0.036, P=0.006). However, thyroid-stimulating hormone (TSH) levels did not show any statistically significant differences among the cases and controls.

Conclusions

Our research demonstrates that, in comparison to controls, children with neurological disorders exhibited a significant decrease in FT4 levels, while TSH levels remained unchanged. This finding provides a reference for potential serum marker of neurological disorders in children. Replication in future studies with the assessment of THs is needed to determine whether thyroid function should be included as a routine screening in these children.
Prediction of remaining service life of lithium battery based on VMD-MC-BiLSTM
Authors: Guangxiong Meng , Zhongnan Liang , Zhongyi Mou
Published: December 2024

The growing popularity of battery-powered products, such as electric vehicles and wearable devices, has increasingly motivated the need to predict the remaining life of lithium-based batteries. This study proposes a method for predicting the remaining life of lithium-based batteries based on a hybrid neural network. First, variational modal decomposition (VMD) was used for noise reduction to maximize retention of the original information and prevent capacity degradation. Second, the trend of capacity decline after noise reduction was modeled and predicted using the combination of bidirectional long short-term memory (BiLSTM) and Monte Carlo (MC) dropout. Finally, experiments were conducted to show that the new method based on the VMD-MC-BiLSTM network achieves good performance for predicting the remaining life of a lithium battery with sufficient confidence level, thereby providing a new approach for optimizing the management of lithium batteries.
Global health benefits associated with a substantial decrease in land transportation emissions during the COVID-19 period
Authors: Zhao Yilong , Chen Yubao , Zhuo Fengqing , Fu Hongbo
Published: December 2024

The changes in global air pollutant concentrations influenced by the COVID-19 lockdown have been widely investigated. The lack of clarity regarding the individual contributions to restricted human activities (i.e., transportation) has limited the understanding of the health impacts of the lockdown. In this study, an efficient chemical transport model (GEOS-Chem) was employed to simulate the concentration changes in air pollutants (PM2.5, NO2, and O3) associated with emission reductions in land transportation and the corresponding health benefits. The simulated results suggested that transportation-related PM2.5, NO2, and O3 reduced by 20%, 36%, and 55%, respectively. The reduction in O3 concentrations presented regional variations, with percentages ranked as follows: China (67%) > India (56%) > Europe (−81%) > the US (−86%), indicating the various intensities of secondary transformations with spatial relevance. The health benefits were also simulated, and the all-caused mortalities were estimated to be 63,547 (95% CI: 47,597, 79,497), 52,685 (95% CI: 32,310, 73,059), and 231,980 (95% CI: 210,373, 253,586) for the reduced concentration of PM2.5, NO2, and O3 globally, respectively. Transportation-related O3 reduction contributed the largest proportion (∼67%) to global health benefits, further emphasizing the global relevance and severity of O3 pollution. Our study confirms that the health benefits of transportation emission reduction during the COVID-19 lockdown were considerable and provides relevant simulated data as supporting evidence. We suggest that further coordinated efforts to restrict certain pollutants worldwide should focus on controlling the global O3 concentrations to protect people from severe O3 exposure.
Comparing species richness and abundance of bumble bees between urban and natural areas using a photographic survey approach
Authors: MacLeod Janelle , Silva-Opps Marina , Sanchez Javier
Published: December 2024

Bumble bees are essential pollinators that provide critical ecosystem services yet, studies are documenting global species declines while recognizing those declines may be understated due to insufficient baseline data. This study investigates bumble bee species richness and abundance across urban and natural sites in Prince Edward Island, Canada, focusing on Charlottetown (urban) and Prince Edward Island National Park (natural). We conducted fieldwork in August and September 2019 using a non-invasive photographic survey technique. We used published keys and sought feedback from citizen science platforms like iNaturalist and Bumble Bee Watch to verify species identification. Our results revealed nine bumble bee species, with Bombus impatiens being the most abundant and Bombus perplexus the rarest. Species richness was higher in natural sites, while urban sites demonstrated moderate levels of bumble bee diversity. Additionally, our findings suggest that sites containing a mix of natural and human-cultivated plant types, predominantly found in our urban study sites, may support higher diversity and evenness levels than those of homogenized plant types (natural or human-cultivated). This research illustrates the practicality of photographic surveys to document the species richness and diversity of bumble bees while avoiding disturbance to populations in urban and natural habitats of Prince Edward Island.
Redefining maladaptation to climate change: a conceptual examination of the unintended consequences of adaptation strategies on ecological-human systems
Authors: Rouzaneh Davoud , Savari Moslem
Published: December 2024

This study presents a redefinition of maladaptation to climate change, offering a comprehensive analysis through qualitative content analysis with an inductive approach, supported by focus group discussions. The main goal was to uncover the conceptual dimensions of the unintended and negative impacts of adaptation strategies on socio-ecological systems, particularly forests and natural resources. The findings indicate that some adaptation measures, though initially aimed at mitigating climate change effects, can paradoxically exacerbate long-term vulnerability, leading to environmental degradation and a diminished adaptive capacity of these systems. In response to these outcomes, the study offers strategic recommendations for managing maladaptation risks. These include adopting integrated adaptation management practices, fostering participatory policymaking, and leveraging local knowledge to enhance both social and ecological resilience. By highlighting the critical need to recognize maladaptation’s potential, this research equips policymakers and natural resource managers with insights into the unintended consequences of adaptation efforts, enabling them to craft more effective strategies for climate resilience.
Validation of selection signatures for coat color in the Podolica Italiana gray cattle breed
Authors: Bruno Silvia , Rovelli Giacomo , Landi Vincenzo , Sbarra Fiorella , Quaglia Andrea , Pilla Fabio , Lasagna Emiliano , Ciani Elena
Published: December 2024

Taurine and indicine gray cattle represent relevant livestock resources in many countries of the world. A gray coat color and pigmented skin, which are common in most of the gray cattle breeds, have been demonstrated to confer better adaptation to solar radiation and thermal stresses. In a previous study adopting the FST-outlier approach with BayeScan v2.0, we identified differentially selected genomic regions in a set of gray cattle breeds, including the Podolica Italiana, and contrasted these findings with four non-gray cattle breeds. More supported signals were detected on bovine chromosomes (BTAs) 2, 4, 14, and 26 that encompassed more than fifty genes known to be directly or indirectly related to one or more steps in pigment biology. In the present study, we aimed to validate the previously observed signals using the same methodological approach on three new Podolica Italiana sample sets (N = 30 animals each). These animals were selected from the ANABIC genetic station during performance tests as being representative of the Podolica Italiana population at three different timeframes separated by approximately 10 years each. We typed these samples to the loci of 23,027 quality-controlled single-nucleotide polymorphisms. We also analyzed the dataset using the haplotype-based approach available in hapFLK v1.4 software. Both the FST-outlier and hapFLK approaches validated the abovementioned signals on BTAs 2, 4, 14, and 26. Moreover, both methods detected additional supported regions on BTAs 7 and 18 that included a total of 42 genes, of which most were already known from literature to be implicated in pigmentation traits.
Vitamin, antioxidant and micronutrient supplementation and the risk of developing incident autoimmune diseases: a systematic review and meta-analysis
Authors: Low Chen Ee , Loke Sean , Chew Nicole Shi Min , Lee Ainsley Ryan Yan Bin , Tay Sen Hee
Published: December 2024

Background

Autoimmune diseases pose significant health challenges worldwide and affect millions. In recent years, there has been growing interest in exploring preventive strategies through nutritional interventions using vitamins, antioxidants, and micronutrients to reduce the risk of developing autoimmune diseases. However, excessive supplementation has also been associated with toxicity.

Objective

We aim to assess how the intake of vitamins, antioxidants and micronutrients affect the risk of developing autoimmune diseases.

Methods

This PRISMA-adherent systematic review involved a systematic search of PubMed, Embase and Cochrane for controlled studies that evaluated the risk of incident autoimmune diseases after supplementation. Random effects meta-analyses were used for primary analysis.

Results

18 studies were included. Overall meta-analyses observed that vitamin D did not influence the risk of autoimmune diseases (RR=0.99, 95%CI: 0.81-1.20). However, among the different vitamin D dosages, subgroup analysis demonstrated that those who were supplemented with 600-800IU/day may have a statistically significant reduction in risk (RR=0.55, 95%CI: 0.38; 0.82). Systematic review suggested that consumption of most vitamins, micronutrients and antioxidants may not have any effect on the risk of autoimmune diseases. Smoking, age, physical or outdoor activity and diet were significant confounding factors that affected the efficacy of such interventions.

Conclusion

We studied the effect of various vitamins, micronutrients and antioxidants on the risk of developing autoimmune diseases. Our study contributes to the evolving landscape of nutritional immunology, providing a foundation for future research to unravel more definite relationships with supplementation and the development of incident autoimmune diseases.

Systematic review registration

https://www.crd.york.ac.uk/prospero/, identifier CRD42024504796.
CD8+ T cell exhaustion in the tumor microenvironment of breast cancer
Authors: Xie Hanghang , Xi Xiaowei , Lei Ting , Liu Hongli , Xia Zhijia
Published: December 2024

CD8+ T cells are crucial cytotoxic components of the tumor immune system. In chronic inflammation, they become low-responsive, a state known as T cell exhaustion (TEX). The aim of immune checkpoint blockade is to counteract TEX, yet its dynamics in breast cancer remain poorly understood. This review defines CD8+ TEX and outlines its features and underlying mechanisms. It also discusses the primary mechanisms of CD8+ TEX in breast cancer, covering inhibitory receptors, immunosuppressive cells, cytokines, transcriptomic and epigenetic alterations, metabolic reprogramming, and exosome pathways, offering insights into potential immunotherapy strategies for breast cancer.
Novel T-cell subsets as non-invasive biomarkers of vascular damage along the predialysis stages of chronic kidney disease
Authors: Martín-Vírgala Julia , Miranda-Prieto Daniel , Fernández-Villabrille Sara , Martín-Carro Beatriz , González-García Nerea , Bande-Fernández Joaquín , Díaz-Corte Carmen , Fernández-Martín José Luis , Alonso-Montes Cristina , Suárez Ana , Panizo Sara , Naves-Díaz Manuel , Rodríguez-Carrio Javier , Carrillo-López Natalia
Published: December 2024

Introduction

Cardiovascular disease is the major cause of premature death in chronic kidney disease (CKD) and vascular damage is often detected belatedly, usually evaluated by expensive and invasive techniques. CKD involves specific risk factors that lead to vascular calcification and atherosclerosis, where inflammation plays a critical role. However, there are few inflammation-related markers to predict vascular damage in CKD. This study aimed to investigate immune populations in pre-dialysis patients to (i) identify subset alterations, (ii) assess longitudinal changes, and (iii) evaluate their applicability as biomarkers of subclinical vascular indices.

Methods

43 pre-dialysis CKD patients in stages CKD-2 to CKD-5 and 38 controls were recruited at baseline and after 18-month follow-up. Aortic stiffness was determined by carotid-femoral pulse wave velocity (PWV) and abdominal aortic calcification was quantified by the Kauppila index on X-rays. Carotid intima-media thickness, the number of carotid plaques and adventitial neovascularization were evaluated by Superb Microvascular Imaging. Peripheral blood mononuclear cells were isolated and immune cell populations were assessed by flow cytometry: senescent T cells (CD4+CD28null), Tang (CD3+CD31+CD184+) and derived subsets, and monocyte subsets (classical, intermediate and non-classical; and ACE expression).

Results

Senescent T cells were increased in CKD. Despite Tang levels were unchanged compared to controls, this subset exhibited enhanced immunosenescence traits (CD28null and inverted CD4+CD8+ ratio) in CKD. Furthermore, Tang were negatively correlated with CKD progression. Slight alterations within monocyte subsets were observed. These findings were validated at the 18-month follow-up. Tang were correlated with several subclinical indices, and further analyses revealed an independent effect on PWV and their potential value as biomarkers. Intermediate monocytes were positively correlated with PWV.

Conclusion

Pre-dialysis CKD stages are hallmarked by alterations in immune cell populations related to vascular homeostasis, including early T-cell immunosenescence traits and a stage-dependent Tang depletion, which was independently related to vascular stiffness. All these features were replicated upon follow-up, thus providing validation toward our results. Our findings pave the ground for future studies addressing the functional contribution of these cellular mediators at the local level, assessing their potential predictive value in the long-term and implementing preventive strategies in the clinical setting.
OCTN1 mediates acetylcholine transport in the A549 lung cancer cells: possible pathophysiological implications
Authors: Pochini Lorena , Tedesco Giusi Elisabetta , Mazza Tiziano , Scalise Mariafrancesca , Indiveri Cesare
Published: December 2024

A role for acetylcholine in cell proliferation, epithelial mesenchymal transition and invasion has been well assessed and related to the presence of the non-neuronal cholinergic system in lung cancer. For the operation of this non-neuronal system, acetylcholine should be released by a transporter mediated non-quantal process. OCTN1 is one of the transporters able to catalyse acetylcholine efflux in vitro and ex vivo. Using the A549 cell line as a lung cancer model, it has been found that these cells express OCTN1 at a higher level with respect to other cancer cells. The transport capacity of OCTN1 extracted from A549 and reconstituted into proteoliposomes reflects the protein expression profile. The properties of the acetylcholine transport mediated by OCTN1 of A549 in terms of specificity to ligands and ability to catalyse efflux of acetylcholine correspond to those previously described for the same transporter in other cells or to those of the human recombinant protein. OCTN1 is the major player in acetylcholine release in A549 and, therefore, may represent a target for inhibitors able to block the acetylcholine action in this type of aggressive tumors.
Fractionated alpha and mixed beam radiation promote stronger pro-inflammatory effects compared to acute exposure and trigger phagocytosis
Authors: Karimi Roshan Mostafa , Belikov Sergey , Ix Melissa , Protti Nicoletta , Balducci Claudia , Dodel Richard , Ross J. Alexander , Lundholm Lovisa
Published: December 2024

Introduction and methods

Aiming to evaluate safety aspects of a recently proposed approach to target Alzheimer’s disease, we mimicked a complex boron neutron capture therapy field using a mixed beam consisting of high- and low-linear energy transfer (LET) radiation, 241Am alpha particles (α) and/or X-ray radiation respectively, in human microglial (HMC3) cells.

Results

Acute exposure to 2 Gy X-rays induced the strongest response in the formation of γH2AX foci 30 min post irradiation, while α- and mixed beam-induced damage (α:X-ray = 3:1) sustained longer. Fractionation of the same total dose (0.4 Gy daily) induced a similar number of γH2AX foci as after acute radiation, however, α- or mixed irradiation caused a higher expression of DNA damage response genes CDKN1A and MDM2 24 h after the last fraction, as well as a stronger decrease in cell viability and clonogenic survival compared to acute exposure. Phosphorylation of STING, followed by phosphorylation of NF-κB subunit p65, was rapidly induced (1 or 3 h, respectively) after the last fraction by all radiation qualities. This led to IL-1β secretion into the medium, strongly elevated expression of pro-inflammatory cytokine genes and enhanced phagocytosis after fractionated exposure to α- and mixed beam-irradiation compared to their acute counterparts 24 h post-irradiation. Nevertheless, all inflammatory changes were returning to basal levels or below 10–14 days post irradiation.

Discussion

In conclusion, we demonstrate strong transient pro-inflammatory induction by daily high-LET radiation in a microglia model, triggering phagocytosis which may aid in clearing amyloid beta, but importantly, from a safety perspective, without long-term alterations.
Calcium-sensor proteins but not bicarbonate ion activate retinal photoreceptor membrane guanylyl cyclase in photoreceptors
Authors: Peshenko Igor V. , Olshevskaya Elena V. , Dizhoor Alexander M.
Published: December 2024

Retinal membrane guanylyl cyclase (RetGC), regulated by guanylyl cyclase activating proteins (GCAPs) via negative calcium-feedback, is one of the most critically important enzymes in vertebrate rod and cone physiology, enabling their sensitivity to light. It was also reported that, similarly to olfactory receptor guanylyl cyclase, bicarbonate anion directly stimulates RetGC activity in photoreceptors as a novel phototransduction-linked regulating factor. We directly tested whether or not RetGC is a bicarbonate-activated enzyme using recombinant human RetGC expressed in HEK293 cells and the native RetGC in mouse retinas. Whereas RetGC in all cases was activated by GCAPs, we found no evidence indicating that bicarbonate can produce direct stimulating effect on RetGC catalytic activity, either basal or GCAP-activated, even at concentrations as high as 100 mM. Instead, near-physiological concentrations of bicarbonate only slightly reduced RetGC activity, whereas concentrations substantially exceeding physiological levels caused a more pronounced reduction of RetGC activity measured in mouse retinas. Our results argue that photoreceptor guanylyl cyclase is not a bicarbonate-stimulated enzyme and rule out the possibility that effects of bicarbonate on photoreceptor physiology are mediated by a direct stimulation of retinal guanylyl cyclase by HCO3−.
Early in vitro results indicate that de-O-acetylated sialic acids increase Selectin binding in cancers
Authors: Das Kakali , Schulte Megan , Gerhart Megan , Bayoumi Hala , Paulson Delayna , Fink Darci M. , Parrish Colin , Willand-Charnley Rachel
Published: December 2024

Cancers utilize a simple glycan, Sialic Acid, to engage in metastatic processes via the Sialic acid (Sia) -Selectin pathway. Selectins recognize and bind to sialylated substrates, resulting in adhesion, migration, and extravasation, however, how deviations from the canonical form of Sia regulate binding to Selectin receptors (E, L, and P) on hemopoietic cells resulting in these metastatic processes, remained a gap in knowledge. De-O-acetylated Sias has been recently shown to be an integral substrate to the binding of sialic acid binding proteins. The two proteins responsible for regulating the acetyl functional group on Sia’s C6 tail, are Sialic acid acetylesterase (SIAE) and Sialic acid O acetyltransferase (CASD1). To elucidate the contribution of functional group alterations on Sia, 9-O and 7,9-O-acetylation of Sia was modulated via the use of CRISRP-Cas9 gene editing and with Sialyl Glycan Recognition Probes, to produce either O-acetylated-Sia or de-O-acetylated- Sia, respectively. In vitro experiments revealed that increased cell surface expression of de-O-acetylated- Sia resulted in an increase in Selectin binding, enhanced cell proliferation, and increased migration capabilities both in lung and colon cancer. These results delineate for the first time the mechanistic contribution of de-O-acetylated-Sia to Selectin binding, reinforcing the importance of elucidating functional group alterations on Sia and their contribution. Without accurate identification of which functionalized form of Sia is being utilized to bind to sialic acid binding proteins, we cannot accurately produce glycan therapeutics with the correct specificity and reactivity, thus this work contributes an integral component in the development of promising therapeutic avenues, for example in the realm of enzyme antibody drug conjugates.
Tracheal reconstructive surgery under ECMO for the treatment of congenital tracheal stenosis in the premature infant: case report
Authors: Xu Qian Ya , Sapana Tamang , Qi Yu , Fu Guo Wei , Guo Long Hui , Ma Wei , Wang Li Li , Zhao Gai , Wang Hai Xia , Zhang Qian
Published: December 2024

Background

Congenital tracheal stenosis (CTS) is a rare but life-threatening malformation of the trachea. Surgical reconstruction is the treatment of choice in symptomatic cases which is highly risky and is rarely performed in extremely premature infants. With this, reporting a case of CTS managed by tracheal reconstructive surgery under ECMO in a baby weighing 1.47 kg at 32 + 1 WOG was the first ever case in China.

Case presentation

A premature newborn with a very low birth weight (VLBW) was admitted to our institute for breathing difficulties, requiring mechanical ventilation, and experienced two unsuccessful attempts of extubation. The team performed tracheal reconstructive surgery supported by ECMO after identifying lower tracheal stenosis through a bronchoscopy examination. One month after the surgery, oxygen support was able to discontinue. The patient's entire hospitalization was incredibly challenging, marked by hemodynamic instability with persistent anemia, and disseminated intravascular coagulation (DIC), which were managed with great care. Despite the difficult stay, a follow-up bronchoscopy revealed no obstruction or tracheal stenosis, leading to a successful discharge.

Conclusion

Advancements in diagnostic techniques and innovative management methods have made diagnosing and treating CTS easier, even in premature infants. Our case is the first in China to successfully undergo tracheal reconstructive surgery supported by ECMO, inspiring future achievements in the medical field.
Case Report: Giant axillary lipoma in an infant
Authors: Ren Haiyang , Lv Haoqiang , Wang Chuanjun , Liu Hao , Liu Xiurui , Wei Hua , Tian Ping
Published: December 2024

Lipoma is a benign mesenchymal tissue tumor, mainly composed of mature adipose cells; it is most common in adults and is rarely observed in children. The clinical data of an infant diagnosed with a giant axillary lipoma admitted to our hospital were analyzed. A 12-month-old girl presented with a large mass in the right axillary region. Imaging examination suggested a mesenchymal tissue tumor and postoperative pathology confirmed lipoma.
Shensu IV maintains the integrity of the glomerular filtration barrier and exerts renal protective effects by regulating endogenous hydrogen sulfide levels
Authors: Zhou Shuhui , Zheng Liping , Zheng Tingxuan , Zhan Haiyan , Lin Qiuyuan , Wei Jiaoao , Huang Yong
Published: December 2024

Background

Nephrotic syndrome has a significant impact on global health, often leading to cardiovascular disease and high mortality due to limited effective treatments. This study investigates the efficacy of Shensu IV in a puromycin aminonucleoside (PAN)-induced rat model of nephropathy.

Methods

Rat models and in vitro podocyte PAN nephropathy models were established with PAN and treated with Shensu IV. Renal function was evaluated by measuring urine output and protein content, while hydrogen sulfide (H2S) and oxidative stress markers were quantified in serum and podocyte lysates. We conducted histological examination on kidney tissues and analyzed molecular markers (CD2AP, nephrin, and PI3K/AKT pathway) using RT-qPCR and Western blot.

Results

Shensu IV significantly improved urine output and proteinuria, and attenuated glomerular damage, fibrosis, and mitochondrial swelling in PAN-treated rats. Mechanistically, Shensu IV enhanced endogenous H2S production, reducing oxidative stress and activating the PI3K/AKT pathway in vivo and in vitro. This facilitated the upregulation of the target genes CD2AP and nephrin, which are critical for maintaining glomerular integrity and improving renal function in PAN nephropathy models.

Conclusion

Shensu IV and NaHS confer renal protection primarily by modulating oxidative stress and restoring the integrity of the glomerular filtration barrier through mechanisms involving the enhancement of the PI3K/AKT pathway and modulation of H2S levels. These findings suggest a promising therapeutic potential for these metabolites in the treatment of nephrotic syndrome.
Synergistic combinations of Angelica sinensis for myocardial infarction treatment: network pharmacology and quadratic optimization approach
Authors: Wang Wen-Di , Fan Xin-Yi , Wei Xiao-Qi , Chai Wang-Jing , Li Fang-He , Gao Kuo , Liu Bin , Guo Shu-Zhen
Published: December 2024

Background and aim

Angelica sinensis (Oliv.) Diels (Danggui, DG), exhibits potential in myocardial infarction (MI) treatment. However, research on its synergistic combinations for cardioprotective effects has been limited owing to inadequate approaches.

Experimental procedure

We identified certain phenolic acids and phthalein compounds in DG. Network pharmacology analysis and experimental validation revealed the components that protected H9c2 cells and reduced lactate dehydrogenase levels. Subsequently, a combination of computational experimental strategies and a secondary phenotypic optimization platform was employed to identify effective component combinations with synergistic interactions. The Chou-Talalay and Zero Interaction Potency (ZIP) models were utilized to quantify the synergistic relationships. The optimal combination identified, Z-Ligustide and Chlorogenic acid (Z-LIG/CGA), was evaluated for its protective effects on cardiac function and cardiomyocytes apoptosis induced by inflammatory in a mouse model of induced by left anterior descending coronary artery ligation. Flow cytometry was further utilized to detect the polarization ratio of M1/M2 macrophages and the expression of inflammatory cytokines in serum was measured, assessing the inhibition of inflammatory responses and pro-inflammatory signaling factors by Z-LIG/CGA.

Key results

Quadratic surface analysis revealed that the Z-LIG/CGA combination displayed synergistic cardioprotective effects (combination index value <1; ZIP value >10). In vivo, Z-LIG/CGA significantly improved cardiac function and reduced the fibrotic area in mice post-MI, surpassing the results in groups treated with Z-LIG or CGA alone. Compared to the MI group, the Z-LIG/CGA group exhibited decreased ratios of the myocardial cell apoptosis-related proteins BAX/Bcl-2 and Cleaved Caspase-3/Caspase-3 in mice. Further research revealed that Z-LIG/CGA treatment significantly increased IL-1R2 levels, significantly decreased IL-17RA levels, and inhibited the activation of p-STAT1, thereby alleviating cell apoptosis after MI. Additionally, the Z-LIG/CGA combination significantly inhibited the ratio of M1/M2 macrophages and suppressed the expression levels of pro-inflammatory cytokines IL-1β, IL-6, IL-17, and TNF-α in the serum.

Conclusion and implications

We successfully identified a synergistic drug combination, Z-LIG/CGA, which improves MI outcomes by inhibiting cardiomyocyte apoptosis and inflammatory damage through modulating macrophage polarization and regulating the IL-1R2/IL-17RA/STAT1 signaling pathway. This study provides a charming paradigm to explore effective drug combinations in traditional Chinese medicine and a promising treatment for MI.
The isolation, bioactivity, and synthesis of natural products from Litsea verticillate with anti-HIV activities
Authors: Yan Jia-Lei , Nan Huiru , Fang Xiaoyu , Long Xiong-En , Jiang Yu , Liu Junyang
Published: December 2024

Natural products isolated from Litsea verticillata have attracted considerable attention from the chemical community due to their unique structures and promising anti-HIV activities. Recent progresses in the isolation and bioactivity studies for these natural molecules were summarized comprehensively. From the 23 previously uncharacterized compounds isolated from the plant Litsea verticillata, litseaverticillol B demonstrated the most potent anti-HIV activity in vitro, with IC50 ranging from 2 to 3 μg/mL. Meanwhile, litseaverticillol E displayed the highest selectivity index (SI = 3.1), indicating a favorable balance between antiviral potency and cellular toxicity. The plausible biosynthetic pathways and the total synthetic approaches for the representative members (litseaverticillols) were introduced in detail.
Transnational economic development: Pakistani and Indian diaspora in focus
Authors: Chauhdry Kinza Tasleem
Published: December 2024

Introduction

Type 2 diabetes mellitus (T2DM) often leads to elevated blood glucose levels and lipid metabolism disorder, which is generally accompanied by dysbiosis of gut microbiota and metabolic dysfunction.

Method

In this study, a mouse model of T2DM was established by feeding a high-fat/sucrose diet combined with injecting a low dose of streptozotocin. The aim of this study was to analyze the regulatory effect of Suaeda salsa extract (SSE) on T2DM and its effect on the intestinal flora of mice.

Results

The results showed that SSE could significantly improve the body weight, fasting blood glucose (FBG), area under the curve (AUC) of the oral glucose tolerance test (OGTT), glycosylated serum protein (GSP) and islet function index. Moreover, 4-week body weight, FBG, AUC of OGTT, GSP, as well as intestinal acetic and butyric acid were significantly better in the SSE-L than in the MET group (p  <  0.05). In addition, it was also found that the potential hypoglycemic mechanism of SSE was related to the expression of Akt serine/threonine kinase (AKT-1) and glucose transporter-2 (GLUT-2) genes. Compared with the model group, SSE intervention significantly increased the abundance of probiotics, such as Soleaferrea, Alloprevotella, Lactobacillus and Faecalibaculum, while decreasing the relative abundance of harmful bacteria, such as Phocaeicola and Bilophila. Analysis of the correlation among intestinal microbiota, short chain fatty acids (SCFAs) and the hypoglycemic index showed that Dwaynesavagella was significantly correlated with acetic, propionic and butyric acid, as well as all the diabetes-related indexes analyzed in this study.

Discussion

Thus, this taxon can potentially be used as a microbiological marker of type 2 diabetes. Taken together, these findings demonstrate that SSE can alleviate T2DM and its complications by improving glycemia-related indicators and modulating the structure of intestinal flora.