bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of 2-(N-aryl-1,2,3-triazol-4-yl) quinoline derivatives as antitubercular agents endowed with InhA inhibitory activity
Authors: Sabt Ahmed , Abdulla Maha-Hamadien , Ebaid Manal S. , Pawełczyk Jakub , Abd El Salam Hayam A. , Son Ninh The , Ha Nguyen Xuan , Vaali Mohammed Mansoor-Ali , Traiki Thamer , Elsawi Ahmed E. , Dziadek Bozena , Dziadek Jaroslaw , Eldehna Wagdy M.
Published: August 2024

The spread of drug-resistant tuberculosis strains has become a significant economic burden globally. To tackle this challenge, there is a need to develop new drugs that target specific mycobacterial enzymes. Among these enzymes, InhA, which is crucial for the survival of Mycobacterium tuberculosis, is a key target for drug development. Herein, 24 compounds were synthesized by merging 4-carboxyquinoline with triazole motifs. These molecules were then tested for their effectiveness against different strains of tuberculosis, including M. bovis BCG, M. tuberculosis, and M. abscessus. Additionally, their ability to inhibit the InhA enzyme was also evaluated. Several molecules showed potential as inhibitors of M. tuberculosis. Compound 5n displayed the highest efficacy with a MIC value of 12.5 μg/mL. Compounds 5g, 5i, and 5n exhibited inhibitory effects on InhA. Notably, 5n showed significant activity compared to the reference drug Isoniazid. Molecular docking analysis revealed interactions between these molecules and their target enzyme. Additionally, the molecular dynamic simulations confirmed the stability of the complexes formed by quinoline-triazole conjugate 5n with the InhA. Finally, 5n underwent in silico analysis to predict its ADME characteristics. These findings provide promising insights for developing novel small compounds that are safe and effective for the global fight against tuberculosis.
Nanocomposite films based on chia (Salvia hispanica L.) flour seeds incorporating antioxidant chitosan nanoparticles
Authors: Morales-Olán Gema , Moreno-Zarate Pedro , Ríos-Corripio María Antonieta , Hernández-Cázares Aleida Selene , Rojas-López Marlon , Luna-Suárez Silvia
Published: August 2024

Chia (Salvia hispanica L.) flour seeds produce films with good barrier properties against water vapor and could be used as food packaging; however, their mechanical properties are poor, which limits their application. The incorporation of nanoparticles into natural polymers is a strategy used to improve the properties of films to increase their applications. Furthermore, nanoparticles can encapsulate antioxidant agents and generate active films. The objective of this study was to evaluate the influence of chia flour (4%–7%), glycerol (15%–25%), and chia extract-loaded chitosan nanoparticles (ChCNp) (0%–0.75%) on the physical, mechanical, barrier, structural and antioxidant properties of chia flour nanocomposite films. Chitosan nanoparticles loaded with antioxidant chia extract were synthesized by ionic gelation and incorporated into the films. The thickness, water vapor permeability, tensile strength, and antioxidant properties of the films were evaluated using a Box-Behnken experimental design. Structural analysis was conducted using the FTIR technique. The results of the ANOVA of the responses were adjusted to second and third order polynomial models obtaining determination coefficients of 0.96–0.99. The water vapor permeability of the films was 3.89 × 10-8–1.68 × 10−7 g mm/Pa s m2, tensile strength was 0.67–3.59 MPa and antioxidant activity was 57.12%–67.84%. The variables presented different effects on the films. Increasing the chia seed flour concentration negatively affected the water vapor permeability but improved the tensile strength and the antioxidant capacity of the films. The increase in glycerol concentration caused the films to become brittle. The nanoparticles had a significant effect on the thickness of the films and improved their mechanical and antioxidant properties. However, they did not show an effect on barrier properties. The results demonstrate that it is possible to obtain nanocomposite films with antioxidant capacity from chia seed flour and with the incorporation of chitosan nanoparticles loaded with antioxidants.
Developmental trajectories of children's playfulness in two- to six-year-olds
Authors: Wustmann Seiler Corina , Duss Isabelle , Rüdisüli Cornelia , Lannen Patricia
Published: August 2024

Even though playfulness has been found to be highly relevant to the development and wellbeing of young children, hardly any longitudinal findings are available on stability and changes in children's playfulness. This study examined developmental trajectories of children's playfulness in two- to six-year-olds over a two-year period and analyzed whether individual and family characteristics and transition to primary school explain these trajectories. The sample included 839 children (47.3% girls, MAge = 4.87 years, SDAge = 1.39) from 38 childcare centers and 47 kindergartens in Switzerland. Children's playfulness was assessed at three measurement time points at one-year intervals using the multidimensional Children's Playfulness Scale to gather parent and teacher reports. Second-order linear growth curve models showed significant interindividual differences in children's playfulness at initial baseline. These differences correlated with effects for age, migrant background, and maternal education. The growth-related processes varied depending on children's age, and the individual dimension of children's playfulness whether an increase, stability, or decline was observed. In particular, social components of playfulness were found to change. On average, children's playfulness increased in early years but decreased from school age onwards. However, closeness in parent–child relationships proved to be supportive of children's playfulness at all time points. The results indicate the significance of positive parenting to children's playfulness, but they also draw attention to how playful qualities can be maintained and more highly valued in the school environment. In general, the study can contribute to a better understanding of the construct of playfulness in childhood.
The perceptions of undergraduate students toward reading contemporary fiction in English: a case study of content-based ESL instruction at a self-financed tertiary institution in Hong Kong
Authors: Lo Noble , Shi Huiwen
Published: August 2024

Introduction

The study explores the effectiveness of teaching English literature to Hong Kong undergraduate students, particularly in a general education course titled “Fiction and Life: Understanding Human Development.” This course marked the first exposure for students to book-length fiction in English and critical response written in English, revealing the efficacy of using fictional works as content-based ESL instruction at the tertiary level in Hong Kong.

Methods

Employing a mixed-methods approach, the study included questionnaires distributed to 310 students and thematic analysis of semi-structured interview data.

Results

Findings indicate a largely positive attitude toward the reading and writing experience, suggesting benefits for ESL teaching and learning in Asia.

Discussion

The study advocates for incorporating English literature into the general education curriculum to foster a more organic and contextualized language acquisition process. This research uniquely contributes to the field by examining student perceptions in a self-financed tertiary institution context, offering new insights that have not been explored before in Hong Kong’s ESL landscape.
Developing valid assessments in the era of generative artificial intelligence
Authors: Kaldaras Leonora , Akaeze Hope O. , Reckase Mark D.
Published: August 2024

Generative Artificial Intelligence (GAI) holds tremendous potential to transform the field of education because GAI models can consider context and therefore can be trained to deliver quick and meaningful evaluation of student learning outcomes. However, current versions of GAI tools have considerable limitations, such as social biases often inherent in the data sets used to train the models. Moreover, the GAI revolution comes during a period of moving away from memorization-based education systems toward supporting learners in developing the ability to apply knowledge and skills to solve real-world problems and explain real-world phenomena. A challenge in using GAI tools for scoring assessments aimed at fostering knowledge application is ensuring that these algorithms are scoring the same construct attributes (e.g., knowledge and skills) as a trained human scorer would score when evaluating student performance. Similarly, if using GAI tools to develop assessments, one needs to ensure that the goals of GAI-generated assessments are aligned with the vision and performance expectations of the learning environments for which these assessments are developed. Currently, no guidelines have been identified for assessing the validity of AI-based assessments and assessment results. This paper represents a conceptual analysis of issues related to developing and validating GAI-based assessments and assessment results to guide the learning process. Our primary focus is to investigate how to meaningfully leverage capabilities of GAI for developing assessments. We propose ways to evaluate the validity evidence of GAI-produced assessments and assessment scores based on existing validation approaches. We discuss future research avenues aimed at establishing guidelines and methodologies for assessing the validity of AI-based assessments and assessment results. We ground our discussion in the theory of validity outlined in the Standards for Educational and Psychological Testing by the American Educational Research Association and discuss how we envision building on the standards for establishing the validity of inferences made from the test scores in the context of GAI-based assessments.
Polyunsaturated fatty acids and diabetic microvascular complications: a Mendelian randomization study
Authors: Liu Bingyang , Liu Ruiyan , Gu Yi , Shen Xiaoying , Zhou Jianqing , Luo Chun
Published: August 2024

Background

Observational studies and clinical trials have implicated polyunsaturated fatty acids (PUFAs) in potentially safeguarding against diabetic microvascular complication. Nonetheless, the causal nature of these relationships remains ambiguous due to conflicting findings across studies. This research employs Mendelian randomization (MR) to assess the causal impact of PUFAs on diabetic microvascular complications.

Methods

We identified instrumental variables for PUFAs, specifically omega-3 and omega-6 fatty acids, using the UK Biobank data. Outcome data regarding diabetic microvascular complications were sourced from the FinnGen Study. Our analysis covered microvascular outcomes in both type 1 and type 2 diabetes, namely diabetic neuropathy (DN), diabetic retinopathy (DR), and diabetic kidney disease (DKD). An inverse MR analysis was conducted to examine the effect of diabetic microvascular complications on PUFAs. Sensitivity analyses were performed to validate the robustness of the results. Finally, a multivariable MR (MVMR) analysis was conducted to determine whether PUFAs have a direct influence on diabetic microvascular complications.

Results

The study indicates that elevated levels of genetically predicted omega-6 fatty acids substantially reduce the risk of DN in type 2 diabetes (odds ratio (OR): 0.62, 95% confidence interval (CI): 0.47–0.82, p = 0.001). A protective effect against DR in type 2 diabetes is also suggested (OR: 0.75, 95% CI: 0.62–0.92, p = 0.005). MVMR analysis confirmed the stability of these results after adjusting for potential confounding factors. No significant effects of omega-6 fatty acids were observed on DKD in type 2 diabetes or on any complications in type 1 diabetes. By contrast, omega-3 fatty acids showed no significant causal links with any of the diabetic microvascular complications assessed.

Conclusions

Our MR analysis reveals a causal link between omega-6 fatty acids and certain diabetic microvascular complications in type 2 diabetes, potentially providing novel insights for further mechanistic and clinical investigations into diabetic microvascular complications.
Metabolic alkalosis in cystic fibrosis: from vascular volume depletion to impaired bicarbonate excretion
Authors: Soleimani Manoocher
Published: August 2024

Cystic fibrosis (CF) is the most common life-threatening genetic disease in the United States and among people of European descent. Despite the widespread distribution of the cystic fibrosis transmembrane conductance regulator (CFTR) along kidney tubules, specific renal phenotypes attributable to CF have not been well documented. Recent studies have demonstrated the downregulation of the apical Cl-/HCO3- exchanger pendrin (Slc26a4) in kidney B-intercalated cells of CF mouse models. These studies have shown that kidneys of both mice and humans with CF have an impaired ability to excrete excess HCO3-, thus developing metabolic alkalosis when subjected to excess HCO3- intake. The purpose of this minireview is to discuss the latest advances on the role of pendrin as a molecule with dual critical roles in acid base regulation and systemic vascular volume homeostasis, specifically in CF. Given the immense prevalence of vascular volume depletion, which is primarily precipitated via enhanced chloride loss through perspiration, we suggest that the dominant presentation of metabolic alkalosis in CF is due to the impaired function of pendrin, which plays a critical role in systemic vascular volume and acid base homeostasis.
Associations between estradiol and hyperuricemia and the mediating effects of TC, TG, and TyG: NHANES 2013–2016
Authors: Zhang Chuxin , Qian Hongyang , Cui Yiwei , Li Xiaojuan , Cheng Yuli , Gao Lin
Published: August 2024

Objectives

To explore the relationship between estradiol (E2) and the incidence of hyperuricemia (HUA) in adult women and to explore whether glucolipid metabolism disorders play a mediating role in mediating this relationship.

Methods

A total of 2,941 participants aged 20–65 years were included in the National Health and Nutrition Examination Survey (NHANES) 2013–2016. Multivariate logistic regression analysis was performed to evaluate the correlations of E2 with HUA. Multivariate linear regression analysis was performed to evaluate the associations between E2 and triglyceride (TG), total cholesterol (TC), and the triglyceride-glucose index (TyG). The restricted cubic spline (RCS) model was used to further explore the association between E2 and HUA and between TG, TC, and TyG and HUA. Mediation analyses were performed to examine whether TC, TG, and TyG mediated the relationship between E2 and HUA.

Results

After adjusting for covariates, logistic regression revealed that ln(E2) was significantly associated with HUA in the female subgroup (p = 0.035) and that the incidence of HUA tended to increase with decreasing ln(E2) (p for trend = 0.026). Linear regression showed that E2 was significantly associated with TC (p = 0.032), TG (p = 0.019), and TyG (p = 0.048). The RCS model showed that ln(E2) was linearly correlated with the incidence of HUA (p-overall = 0.0106, p-non-linear = 0.3030). TC and TyG were linearly correlated with HUA (TC: p-overall = 0.0039, p-non-linear = 0.4774; TyG: p-overall = 0.0082, p-non-linear = 0.0663), whereas TG was non-linearly correlated with HUA. Mediation analyses revealed that TC, TG, and TyG significantly mediated the relationship between ln(E2) and HUA (TC, indirect effect: −0.00148, 7.5%, p = 0.008; TG, indirect effect: −0.00062, 3.1%, p = 0.004; TyG, indirect effect: −0.00113, 5.6%, p = 0.016).

Conclusion

In conclusion, this study demonstrated that compared with women aged 20–45 years, women aged 45–55 years and 55–65 years had lower E2 levels and a greater incidence of HUA. E2 levels and the incidence of HUA were negatively associated in female individuals but not in male individuals. In addition, TC, TG, and TyG, which are markers of glucolipid metabolism, played a mediating role in the association between E2 and HUA.
Evaluating the role of aldosterone synthesis on adrenal cell fate
Authors: Aminuddin Amnani , Brown Morris J. , Azizan Elena Aisha
Published: August 2024

Hypertension affects one-third of the adult population worldwide, with primary aldosteronism (PA) accounting for at least 5-10% of these cases. The aldosterone synthase enzyme (CYP11B2) plays a pivotal role in PA manifestation, as increased expression of CYP11B2 leads to excess aldosterone synthesis. Physiological expression of CYP11B2 in humans is normally limited to cells of the adrenal zona glomerulosa under tight homeostatic regulation. In PA, however, there are CYP11B2-positive lesions in the adrenal cortex that autonomously secrete aldosterone, highlighting the dysregulation of adrenal cortex zonation and function as a key aspect of PA pathogenesis. Thus, this review aims to summarize the development of the adrenal glands, the key regulators of adrenal cortex homeostasis, and the dysregulation of this homeostasis. It also discusses the development of CYP11B2 inhibitors for therapeutic use in patients with hypertension, as well as the current knowledge of the effects of CYP11B2 inhibition on adrenal cortex homeostasis and cell fate. Understanding the control of adrenal cell fate may offer valuable insights into both the pathogenesis of PA and the development of alternative treatment approaches for PA.
The role of calcium channels in osteoporosis and their therapeutic potential
Authors: Hao Ying , Yang Ningning , Sun Mengying , Yang Shangze , Chen Xingjuan
Published: August 2024

Osteoporosis, a systemic skeletal disorder marked by diminished bone mass and compromised bone microarchitecture, is becoming increasingly prevalent due to an aging population. The underlying pathophysiology of osteoporosis is attributed to an imbalance between osteoclast-mediated bone resorption and osteoblast-mediated bone formation. Osteoclasts play a crucial role in the development of osteoporosis through various molecular pathways, including the RANK/RANKL/OPG signaling axis, cytokines, and integrins. Notably, the calcium signaling pathway is pivotal in regulating osteoclast activation and function, influencing bone resorption activity. Disruption in calcium signaling can lead to increased osteoclast-mediated bone resorption, contributing to the progression of osteoporosis. Emerging research indicates that calcium-permeable channels on the cellular membrane play a critical role in bone metabolism by modulating these intracellular calcium pathways. Here, we provide an overview of current literature on the regulation of plasma membrane calcium channels in relation to bone metabolism with particular emphasis on their dysregulation during the progression of osteoporosis. Targeting these calcium channels may represent a potential therapeutic strategy for treating osteoporosis.
Model predictive control for single-phase cascaded H-bridge photovoltaic inverter system considering common-mode voltage suppression
Authors: Wei Xinwei , Tao Wanyu , Fu Xunbo
Published: August 2024

In this article, a model predictive control (MPC) with common-mode voltage (CMV) suppression is proposed for single-phase cascaded H-bridge (CHB) inverters, which can also simultaneously achieve control objectives of grid-connected current tracking, voltages balancing of different H-bridge submodules on the DC-side and switching frequency reduction. To suppress high-frequency components of the common-mode voltage without additional switching devices, the algorithm proposed designs the predicted and reference values of the CMV and incorporates them in the cost function. At the same time, the capacitor voltages balancing control is integrated in the calculation of the optimal modulation function of the H-bridge, which reduces the complexity of control effectively. Besides, switching times of the MOSFETs are compared in two cycles. The cost function is constructed to represent comprehensive effect of the control. Finally, an experiment is performed on the hardware-in-the-loop experimental platform. The experimental results show that the proposed algorithm can offer a better voltage THD and reduce the times of switch action by nearly half while maintaining high-precision current tracking and maximum power point of photovoltaic modules, which alleviate the potential electromagnetic interference and cabling problem.
Effects of autumn tillage with straw return on soil physical characteristics of corn fields in the eastern loess plateau
Authors: Fan Yuchen , Yuan Yaqi , Li Tao , Lin Wen , Tang Xiwang , Liang Gaimei , Li Nana
Published: August 2024

The implementation of unsuitable tillage practices has the potential to disrupt the structure integrity of the ploughed layer, as well as to influence the physical parameters of the soil. The application of a reasonable tillage method has been demonstrated to result in an improvement in the physical quality of the soil. Three autumn tillage practices have been implemented at the Dongyang Experimental Station of Shanxi Agricultural University since 2016: no-tillage with straw mulch (NTS), autumn rotary tillage with straw incorporation (RTS), and autumn plough tillage with straw incorporation (PTS). The impact of autumn tillage practices on soil physical quality in the 0–30 cm profile of spring corn fields was evaluated following the corn harvest in 2018 and 2019. The results showed that compared to the NTS treatment, the application of RTS was found to have decreased significantly by 9.6%–24.2% in soil bulk density, while it increased significantly by 12.8%–34.0% in total porosity and by 43.5%–146.4% in macroporosity at a depth of 5–10 cm. In comparison to the NTS treatment, the adoption of PTS was found to decrease significantly by 10.7%–30.5% soil bulk density, while it increased significantly by 9.9%–42.7% the total porosity and 23.1%–202.8% the macroporosity at a depth of 0–10 cm. Furthermore, the soil microporosity significantly increase of 7.5%–11.1% under the RTS treatment at the 0–5 cm soil depth and 7.7%–11.2% under the PTS treatment at the 10–20 cm soil depth. Soil physical quality index (SQI) significantly increase under the RTS and PTS treatments, with a 41.26% and 57.57% improvement, respectively, in comparison to the NTS treatment. In summary, the adoption of autumn tillage with straw return (RTS and PTS) demonstrated a reduction in soil bulk density, an increase in soil porosity, macroporosity, and a promotion of capillary porosity, and promoted the improvement of soil physical quality on the Eastern Loess Plateau when compared to no-tillage with straw mulch (NTS).
Role of tumor-associated macrophages in hepatocellular carcinoma: impact, mechanism, and therapy
Authors: Zhang Yinqi , Han Guoyong , Gu Jian , Chen Zhiqiang , Wu Jindao
Published: August 2024

Hepatocellular carcinoma (HCC) is a highly frequent malignancy worldwide. The occurrence and progression of HCC is a complex process closely related to the polarization of tumor-associated macrophages (TAMs) in the tumor microenvironment (TME). The polarization of TAMs is affected by a variety of signaling pathways and surrounding cells. Evidence has shown that TAMs play a crucial role in HCC, through its interaction with other immune cells in the TME. This review summarizes the origin and phenotypic polarization of TAMs, their potential impacts on HCC, and their mechanisms and potential targets for HCC immunotherapy.
Tranexamic acid: a narrative review of its current role in perioperative medicine and acute medical bleeding
Authors: Bouras Marwan , Bourdiol Alexandre , Rooze Paul , Hourmant Yannick , Caillard Anaïs , Roquilly Antoine
Published: August 2024

Purpose

Tranexamic acid (TXA) is the most widely prescribed antifibrinolytic for active bleeding or to prevent surgical bleeding. Despite numerous large multi-center randomized trials involving thousands of patients being conducted, TXA remains underutilized in indications where it has demonstrated efficacy and a lack of harmful effects. This narrative review aims to provide basic concepts about fibrinolysis and TXA’s mode of action and is focused on the most recent and important trials evaluating this drug in different hemorrhagic situations.

Methods

We selected every low bias RCT, and we highlighted their strengths and limitations throughout this review.

Principal findings

While TXA appears to have a favorable benefit–risk ratio in most situations (trauma, obstetrics, at-risk for bleeding surgeries) evidence of benefit is lacking in certain medical settings (SAH, digestive bleeding).

Conclusion

Although in some situations the drug’s effect on significant outcomes is modest, its favorable safety profile allows it to be recommended for trauma patients, in obstetrics, and in scheduled surgeries at risk of bleeding. However, it cannot be recommended in cases of spontaneous intracranial bleeding, subarachnoid hemorrhage (SAH), or gastrointestinal bleeding.
Three new species of Laccaria (Agaricales, Basidiomycota) from Southwest China (Yunnan) based on morphological and multi-gene sequence data
Authors: Li Jing , Che Nian-Jie , Cui Yang-Yang
Published: August 2024

Introduction

The genus Laccaria has been reported from temperate and tropical areas and is an important constituent in forest ecosystems. However, the species diversity of Laccaria in Southwest China (Yunnan) has been underestimated.

Methods

In this paper, descriptions based on morphological and multi-gene sequence data from internal transcribed spacer (ITS) region, large subunit ribosomal RNA gene (nrLSU), translation elongation factor 1-α (TEF1α) and the polymerase II second largest subunit (RPB2) of three new Laccaria species from Southwest China (Yunnan) are reported.

Results

Two of these were characterized by orange pileus and globose to subglobose basidiospores: L. cinnabarina and L. spinulosa. While L. cinnabarina has orange red colored basidiocarps with conspicuously pellucid-striate pattern, and a fibrillose stipe with longitudinally striations, L. spinulosa has a brownish orange to brown fruiting body with light white pruinae and 2-spored basidia. Laccaria longistriata is characterized by brown to flesh-colored basidioma, prominently striate to sulcate pileus and globose to subglobose basidiospores.

Discussion

The three new species were described, illustrated and compared with closely related species in morphology and phylogeny.
Synergistic removal of Staphylococcus aureus biofilms by using a combination of phage Kayvirus rodi with the exopolysaccharide depolymerase Dpo7
Authors: Duarte Ana Catarina , Fernández Lucía , Jurado Andrea , Campelo Ana Belén , Shen Yang , Rodríguez Ana , García Pilar
Published: August 2024

Introduction

Bacteriophages have been shown to penetrate biofilms and replicate if they find suitable host cells. Therefore, these viruses appear to be a good option to tackle the biofilm problem and complement or even substitute more conventional antimicrobials. However, in order to successfully remove biofilms, in particular mature biofilms, phages may need to be administered along with other compounds. Phage-derived proteins, such as endolysins or depolymerases, offer a safer alternative to other compounds in the era of antibiotic resistance.

Methods

This study examined the interactions between phage Kayvirus rodi with a polysaccharide depolymerase (Dpo7) from another phage (Rockefellervirus IPLA7) against biofilms formed by different Staphylococcus aureus strains, as determined by crystal violet staining, viable cell counts and microscopy analysis.

Results and discussion

Our results demonstrated that there was synergy between the two antimicrobials, with a more significant decreased in biomass and viable cell number with the combination treatment compared to the phage and enzyme alone. This observation was confirmed by microscopy analysis, which also showed that polysaccharide depolymerase treatment reduced, but did not eliminate extracellular matrix polysaccharides. Activity assays on mutant strains did not identify teichoic acids or PNAG/PIA as the exclusive target of Dpo7, suggesting that may be both are degraded by this enzyme. Phage adsorption to S. aureus cells was not significantly altered by incubation with Dpo7, indicating that the mechanism of the observed synergistic interaction is likely through loosening of the biofilm structure. This would allow easier access of the phage particles to their host cells and facilitate infection progression within the bacterial population.
Trematocine-derived antimicrobial peptides from the Antarctic fish Trematomus bernacchaii: potent antibacterial agents against ESKAPE pathogens
Authors: Squitieri Damiano , Massaro Federica , Graziano Monica Mollica , Borocci Stefano , Cacaci Margherita , Di Vito Maura , Porcelli Fernando , Rosato Roberto , Ceccacci Francesca , Sanguinetti Maurizio , Buonocore Francesco , Bugli Francesca
Published: August 2024

Introduction

This study investigated the interaction with membrane mimetic systems (LUVs), bacterial membranes, the CD spectra, and the bactericidal activity of two designed trematocine mutants, named Trem-HK and Trem-HSK. Mutants were constructed from the scaffold of Trematocine (Trem), a natural 22-amino acid AMP from the Antarctic fish Trematomus bernacchii, aiming to increase their positive charge.

Methods

The selectivity of the designed AMPs towards bacterial membranes was improved compared to Trematocine, verified by their interaction with different LUVs and their membranolytic activity. Additionally, their α-helical conformation was not influenced by the amino acid substitutions. Our findings revealed a significant enhancement in antibacterial efficacy against ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacteriaceae family) pathogens for both Trem-HK and Trem-HSK.

Results

Firstly, we showed that the selectivity of the two new designed AMPs towards bacterial membranes was greatly improved compared to Trematocine, verifying their interaction with different LUVs and their membranolytic activity. We determined that their α-helical conformation was not influenced by the amino acid substitutions. We characterized the tested bacterial collection for resistance traits to different classes of antibiotics. The minimum inhibitory and bactericidal concentration (MIC and MBC) values of the ESKAPE collection were reduced by up to 80% compared to Trematocine. The bactericidal concentrations of Trematocine mutants showed important membranolytic action, evident by scanning electron microscopy, on all tested species. We further evaluated the cytotoxicity and hemolytic activity of the mutants. At 2.5 μM concentration, both mutants demonstrated low cytotoxicity and hemolysis, indicating selectivity towards bacterial cells. However, these effects increased at higher concentrations.

Discussion

Assessment of in vivo toxicity using the Galleria mellonella model revealed no adverse effects in larvae treated with both mutants, even at concentrations up to 20 times higher than the lowest MIC observed for Acinetobacter baumannii, suggesting a high potential safety profile for the mutants. This study highlights the significant improvement in antibacterial efficacy achieved by increasing the positive charge of Trem-HK and Trem-HSK. This improvement was reached at the cost of reduced biocompatibility. Further research is necessary to optimize the balance between efficacy and safety for these promising AMPs.
Pan-cancer analysis and single-cell analysis reveals FAM110B as a potential target for survival and immunotherapy
Authors: Li Yuwei , Li Xiaoxi , Wu Bihua , Su Shuangyan , Su Yunpeng , Guo Le
Published: August 2024

Background: FAM110B belongs to the family that has a 110 sequence similarity (FAM110) and is located in the centrosome and mitotic spindle. FAM110B has been linked to tumor cell growth in earlier research. Uncertainty exists regarding FAM110B’s function within the tumor microenvironment is unclear as well as pan-cancer.

Methods: In order to assess the variation in FAM110B expression within normal and pan-cancer tissues, we combined the TCGA and GTEx databases. The cBioPortal database and the GSCALite platform were used to examine the variation in genome and methylation alteration of FAM110B. Cox regression, Kaplan-Meier, and SangerBox were employed to examine the clinical features and prognosis of FAM110B and pan-cancer. The purpose of the correlational research was to investigate the associations within immunerelated genes, tumor mutation burden, microsatellite instability, immune-related genes, and immunological checkpoints and FAM110B expression. ESTIMATE, EPIC, QUANTISEQ, and MCPCOUNTER methods were used to calculate the interaction among FAM110B expression as well as the tumor immune microenvironment. The immunoinfiltration and function of FAM110B were analyzed by single-cell databases (TISCH and CancerSEA). Finally, we evaluated the sensitivity of FAM110B to small-molecule medications through GDSC and CTRP databases.

Results: The transcription and protein expression of FAM110B varies significantly throughout cancer types, and this has predictive value for the prognosis of some tumors; including brain lower grade glioma (LGG), stomach adenocarcinoma (STAD), pancreatic adenocarcinoma (PAAD), etc. In the tumor microenvironment, the expression level of FAM110B was associated with immune cell infiltration, immune checkpoint immune regulatory genes, tumor mutational burden, and microsatellite fragility to a certain extent.

Conclusion: This work investigates the possibility of utility of FAM110B as a marker to forecast pan-cancer immunotherapy response, providing a theoretical basis for cancer therapy.
Discovery of an 8-oxoguanine regulator PCBP1 inhibitor by virtual screening and its synergistic effects with ROS-modulating agents in pancreatic cancer
Authors: Qiao Kexiong , Xu Chengjie , Zhang Chaolei , Wang Qianqian , Jiang Jun , Chen Zongrong , Zhou Liangjing , Jia Shengnan , Cao Liping
Published: August 2024

Introduction: Drugs that target reactive oxygen species (ROS) metabolism have progressed the treatment of pancreatic cancer treatment, yet their efficacy remains poor because of the adaptation of cancer cells to high concentration of ROS. Cells cope with ROS by recognizing 8-oxoguanine residues and processing severely oxidized RNA, which make it feasible to improve the efficacy of ROS-modulating drugs in pancreatic cancer by targeting 8-oxoguanine regulators.

Methods: Poly(rC)-binding protein 1 (PCBP1) was identified as a potential oncogene in pancreatic cancer through datasets of The Cancer Genome Atlas (TCGA) project and Gene Expression Omnibus (GEO). High-throughput virtual screening was used to screen out potential inhibitors for PCBP1. Computational molecular dynamics simulations was used to verify the stable interaction between the two compounds and PCBP1 and their structure–activity relationships. In vitro experiments were performed for functional validation of silychristin.

Results: In this study, we identified PCBP1 as a potential oncogene in pancreatic cancer. By applying high-throughput virtual screening, we identified Compound 102 and Compound 934 (silychristin) as potential PCBP1 inhibitors. Computational molecular dynamics simulations and virtual alanine mutagenesis verified the structure–activity correlation between PCBP1 and the two identified compounds. These two compounds interfere with the PCBP1–RNA interaction and impair the ability of PCBP1 to process RNA, leading to intracellular R loop accumulation. Compound 934 synergized with ROS agent hydrogen peroxide to strongly improve induced cell death in pancreatic cancer cells.

Discussion: Our results provide valuable insights into the development of drugs that target PCBP1 and identified promising synergistic agents for ROS-modulating drugs in pancreatic cancer.
Association between a combination of cognitively stimulating leisure activities and long-chain polyunsaturated fatty acid intake on cognitive decline among community-dwelling older Japanese individuals
Authors: Tokuda Hisanori , Horikawa Chika , Nishita Yukiko , Kaneda Yoshihisa , Obata Hidenori , Rogi Tomohiro , Izumo Takayuki , Nakai Masaaki , Shimokata Hiroshi , Otsuka Rei
Published: August 2024

Multifactorial lifestyle approaches could be more effective than a single factor for maintaining cognitive function. This study investigated the association of combining cognitively stimulating leisure activities (CSLAs), including puzzles, quizzes, and cognitive training games, with intake of long-chain polyunsaturated fatty acids (LCPUFAs), including docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and arachidonic acid (ARA), on cognitive function in the older Japanese individuals without dementia. Participants were community-dwelling Japanese individuals without a self-reported history of dementia (n = 906, aged 60–88 years) from datasets of a 2-year longitudinal study (baseline: 2006–2008 and follow-up: 2008–2010). CSLA engagement and LCPUFA intake were divided into high and low groups according to frequency (≥once/week and <once/week) for CSLA engagement and median intake level for LCPUFA intake according to sex, then categorized into four groups. The associations of multivariate-adjusted odds ratio (OR) for a cognitive decline, shown as a decrease in the Mini-Mental State Examination score by 2 or more points, and the combination of CSLA engagement with LCPUFA intake were assessed using a multiple logistic regression model. Subgroup analysis involved participants with low DHA and EPA intakes (n = 303; median intake, 325 mg/day), mirroring those in North America. The HIGH-CSLA/HIGH-ARA group cumulatively yielded a lower OR for cognitive decline (0.41; 95% confidence interval, 0.25–0.70) than did the LOW-CSLA/LOW-ARA group (p for trend = 0.001). In the subgroup analysis, the OR for the HIGH-CSLA/HIGH-DHA group was notably reduced (0.31; 95% confidence interval, 0.11–0.87; p for trend = 0.025) compared with the LOW-CSLA/LOW-DHA group. High CSLA engagement frequency combined with high ARA intake may cumulatively reduce the risk of cognitive decline among older Japanese individuals. Furthermore, combining CSLA engagement frequency with DHA intake could have a positive association with maintaining cognitive function among older individuals, particularly those with low DHA and EPA intakes.
Neurocognitive mechanisms of emotional interference in native and foreign languages: evidence from proficient bilinguals
Authors: Del Maschio Nicola , Sulpizio Simone , Bellini Camilla , Del Mauro Gianpaolo , Giannachi Matteo , Buga Duygu , Fedeli Davide , Perani Daniela , Abutalebi Jubin
Published: August 2024

Currently available data show mixed results as to whether the processing of emotional information has the same characteristics in the native (L1) as in the second language (L2) of bilinguals. We conducted a functional magnetic resonance imaging (fMRI) experiment to shed light on the neurocognitive mechanisms underlying bilinguals’ emotional processing in L1 and L2 during an emotional interference task (i.e., the Emotional Stroop Task – EST). Our sample comprised proficient Italian-English bilinguals who learned their L2 during childhood mainly in instructional rather than immersive contexts. In spite of no detectable behavioural effects, we found stronger brain activations for L1 versus L2 emotional words in sectors of the posteromedial cortex involved in attention modulation, episodic memory, and affective processing. While fMRI findings are consistent with the hypothesis of a stronger emotional resonance when processing words in a native language, our overall pattern of results points to the different sensitivity of behavioural and hemodynamic responses to emotional information in the two languages of bilingual speakers.
Longitudinal assessment of glymphatic changes following mild traumatic brain injury: Insights from perivascular space burden and DTI-ALPS imaging
Authors: Zhuo Jiachen , Raghavan Prashant , Li Jiang , Roys Steven , Njonkou Tchoquessi Rosy Linda , Chen Hegang , Wickwire Emerson M. , Parikh Gunjan Y. , Schwartzbauer Gary T. , Grattan Lynn M. , Wang Ze , Gullapalli Rao P. , Badjatia Neeraj
Published: August 2024

Introduction

Traumatic brain injury (TBI) even in the mild form may result in long-lasting post-concussion symptoms. TBI is also a known risk to late-life neurodegeneration. Recent studies suggest that dysfunction in the glymphatic system, responsible for clearing protein waste from the brain, may play a pivotal role in the development of dementia following TBI. Given the diverse nature of TBI, longitudinal investigations are essential to comprehending the dynamic changes in the glymphatic system and its implications for recovery.

Methods

In this prospective study, we evaluated two promising glymphatic imaging markers, namely the enlarged perivascular space (ePVS) burden and Diffusion Tensor Imaging-based ALPS index, in 44 patients with mTBI at two early post-injury time points: approximately 14 days (14Day) and 6–12 months (6–12Mon) post-injury, while also examining their associations with post-concussion symptoms. Additionally, 37 controls, comprising both orthopedic patients and healthy individuals, were included for comparative analysis.

Results

Our key findings include: (1) White matter ePVS burden (WM-ePVS) and ALPS index exhibit significant correlations with age. (2) Elevated WM-ePVS burden in acute mTBI (14Day) is significantly linked to a higher number of post-concussion symptoms, particularly memory problems. (3) The increase in the ALPS index from acute (14Day) to the chronic (6–12Mon) phases in mTBI patients correlates with improvement in sleep measures. Furthermore, incorporating WM-ePVS burden and the ALPS index from acute phase enhances the prediction of chronic memory problems beyond socio-demographic and basic clinical information.

Conclusion

ePVS burden and ALPS index offers distinct values in assessing glymphatic structure and activity. Early evaluation of glymphatic function could be crucial for understanding TBI recovery and developing targeted interventions to improve patient outcomes.
Examining child schooling/care location and child temperament as predictors of restaurant-related behaviors during the COVID-19 pandemic: findings from a nationally representative survey
Authors: Goldsmith Juliana , Ferrante Mackenzie J. , Tauriello Sara , Epstein Leonard H. , Leone Lucia A. , Anzman-Frasca Stephanie
Published: August 2024

Purpose

Emerging research highlights impacts of the COVID-19 pandemic on U.S. families, including changes in eating behavior and increased child body mass index. Aims of the present study were to examine whether child temperament and at-home vs. out-of-home childcare/school predicted families’ restaurant-related behaviors during the pandemic. Examining energy balance-related behaviors, like restaurant patronage, during the pandemic can help better understand lasting impacts on child health behaviors and health outcomes.

Methods

An online survey was administered to U.S. parents with a 4-to-8-year-old child in October 2020 (n = 1,000). Linear and logistic regression examined whether child temperament and at home vs. out-of-home childcare/school predicted: (1) the frequency the child consumed restaurant meals (take-out, delivery, dine-in), (2) who chose the child’s restaurant meal, and (3) parent-reported reasons for the child’s meal choice. Income, education, employment, race/ethnicity, and regional COVID-19 restrictions were tested as covariates.

Results

Parents with children higher on negative affectivity reported more frequent restaurant use in-person (p < 0.05) and via delivery (p < 0.05) compared to parents of children lower on negativity. Child negativity was also linked with parent-reported reasons for children’s restaurant meal choices. Parents of children receiving at-home childcare/schooling used delivery services less frequently than those receiving out-of-home care or schooling (p < 0.01).

Conclusion

These findings suggest that individual and family factors may impact restaurant use and the meal selection process for children using restaurants during and beyond the COVID-19 era. Continued examination of individual differences in the impacts of the COVID-19 pandemic can facilitate intervention and policy approaches that fit with different families’ needs.
Diagnostic and prognostic significance of ALU-based cell-free DNA in colorectal cancer: a systematic review and meta-analysis
Authors: Taghizadeh-Teymorloei Mohammad , Alizadeh Leila , Matin Somaieh , Jafari-Koshki Tohid , Karimi Abbas
Published: August 2024

Introduction

Colorectal cancer (CRC) is a major global health concern. This study aimed to investigate the role of ALU-based cell-free DNA (cfDNA) in the diagnosis and prognosis of CRC.

Methods

We selected relevant literature from PubMed, Scopus, Web of Science, EMBASE, and Science Direct databases based on strict inclusion and exclusion criteria. 17 eligible studies were included in the final analysis (13 studies for diagnostic and 4 studies for prognostic meta-analysis). The search covered relevant publications up to July 1, 2024.

Results

The pooled sensitivity, specificity, and diagnostic odds ratios (DOR) of ALU-based cfDNA in CRC diagnosis were 0.81 (95% CI= [0.70, 0.89]), 0.90 (95% CI= [0.70, 0.96]), and 40.58 (95% CI= [17.87, 92.19]), respectively. The area under the ROC curve was 0.92 (95% CI= [0.89, 0.94]). Patients with higher concentrations of plasma/serum ALU-based cfDNA had poorer overall survival (OS) (pooled hazard ratio = 2.33 ([95% CI= [1.80, 3.03]).

Conclusion

The current evidence supports the utility of circulating ALU as a promising non-invasive diagnostic and prognostic tool for CRC. Furthermore, as a potential biomarker, ALU-based cfDNA could play a significant role in clinical application.

Clinical implications

The evidence suggests that circulating ALU-based cell-free DNA (cfDNA) holds promise as a non-invasive diagnostic and prognostic tool for colorectal cancer, potentially enhancing clinical decision-making.

Systematic review registration

https://www.crd.york.ac.uk/prospero/, identifier PROSPERO (CRD42023486369).
External breast prostheses after mastectomy: production and selection of a low-cost functional model to be performed in developing countries
Authors: Vieira René Aloisio da Costa , Ibrahim Matheus Sampaio , de Souza Araujo Lucas Guimarães , Souza Junior José de Assis e , de Freitas Carla Simone Moreira , de Oliveira Luiz Carlos Navarro
Published: August 2024

Introduction

Breast cancer is one of the most common types of cancer affecting women. Despite advancements in early diagnosis, neoadjuvant therapy, and various treatment modalities, mastectomy remains a common procedure for many women. Although some women opt for reconstructive surgery (BR), many do not have the indication, desire, or opportunity to undergo this procedure.

Methods

An easily manufactured, washable, lightweight, and inexpensive external breast prosthesis (EBP) model was developed specifically for the study. Participants were presented with five EBP models–one commercially available, three manufactured options, and one created for the study–and were asked to choose a prosthesis. We also evaluated the factors associated with non-adherence to EBP among women who had undergone mastectomy without BR. The chi-square test was used to assess adherence or non-adherence to EBP, while logistic regression was used to identify factors associated with non-adherence.

Results

We introduced a low-cost, lightweight, washable EBP model. When participants were asked to choose between two prostheses, the silicone prosthesis was the first choice for 33.9% of the participants, while the prosthesis created for the study emerged as the second choice for 70.5%. Out of the 72 women assessed, 45.8% (33) opted not to use any of the EBP models. Our analysis revealed that age and BMI were significantly associated with non-use of EBP.

Conclusion

Multiple barriers contribute to non-adherence to EBP, underscoring the need for interventions aimed at improving patient knowledge and adherence. This study introduces a lightweight, easily reproducible, and low-cost EBP model.