bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic value and immune landscapes of TERT promoter methylation in triple negative breast cancer
Authors: Lin Fei , Huang Jiajia , Zhu Wancui , Jiang Tongchao , Guo Jia , Xia Wen , Chen Miao , Guo Ling , Deng Wuguo , Lin Huanxin
Published: July 2023

Background

Treatment options for patients with triple-negative breast cancer (TNBC) remain limited to mainstay therapies owing to a lack of efficacious therapeutic targets. Accordingly, there is an urgent need to discover and identify novel molecular targets for the treatment and diagnosis of this disease. In this study, we analyzed the correlation of telomerase reverse transcriptase (TERT) methylation status with TERT expression, prognosis, and immune infiltration in TNBC and identified the role of TERT methylation in the regulation TNBC prognosis and immunotherapy.

Methods

Data relating to the transcriptome, clinicopathological characteristics and methylation of TNBC patients were obtained from The Cancer Genome Atlas (TCGA) database. TERT expression levels and differential methylation sites (DMSs) were detected. The correlations between TERT expression and DMSs were calculated. Kaplan–Meier curves was plotted to analyze the relationship between the survival of TNBC patients and the DMSs. The correlations of DMSs and TERT expression with several immunological characteristics of immune microenvironment (immune cell infiltration, immunomodulators, immune-related biological pathways, and immune checkpoints) were assessed. The results were validated using 40 TNBC patients from Sun Yat-sen University Cancer Center (SYSUCC).

Results

Six DMSs were identified. Among them, four sites (cg11625005, cg07380026, cg17166338, and cg26006951) were within the TERT promoter, in which two sites (cg07380026 and cg26006951) were significantly related to the prognosis of patients with TNBC. Further validation using 40 TNBC samples from SYSUCC showed that the high methylation of the cg26006951 CpG site was associated with poor survival prognosis (P=0.0022). TERT expression was significantly correlated with pathological N stage and clinical stage, and cg07380026 were significantly associated with pathological T and N stages in the TCGA cohort. Moreover, the methylation site cg26006951, cg07380026 and TERT expression were significantly correlated with immune cell infiltration, common immunomodulators, and the level of the immune checkpoint receptor lymphocyte activation gene 3 (LAG-3) in TNBC patients.

Conclusion

TERT promotertypermethylation plays an important role in TERT expression regulation and tumor microenvironment in TNBC. It is associated with overall survival and LAG-3 expression. TERT promoter hypermethylation may be a potential molecular biomarker for predicting response to the TERT inhibitors and immune checkpoint inhibitors in TNBC.
Lipedema stage affects adipocyte hypertrophy, subcutaneous adipose tissue inflammation and interstitial fibrosis
Authors: Kruppa Philipp , Gohlke Sabrina , Łapiński Kamila , Garcia-Carrizo Francisco , Soultoukis George A. , Infanger Manfred , Schulz Tim J. , Ghods Mojtaba
Published: July 2023

Introduction

Lipedema is a painful subcutaneous adipose tissue (SAT) disease characterized by adipocyte hypertrophy, immune cell recruitment, and fibrosis in the affected areas. These features are thought to contribute to the development and progression of the condition. However, the relationship between lipedema disease stage and the associated adipose tissue changes has not been determined so far.

Methods

SAT biopsies of 32 lipedema patients, ranging across the pathological stages I to III, and 14 BMI- and age-matched controls were harvested from lipedema-affected thighs and non-symptomatic lower abdominal regions. Histological and immunohistochemical (IHC) staining and expression analysis of markers for adipogenesis, immunomodulation, and fibrosis were performed on the tissue biopsies.

Results

Lipedema patients showed increased adipocyte areas and a stage-dependent shift towards larger cell sizes in the thighs. Lipedema SAT was linked with increased interstitial collagen accumulation in the thighs, but not the lower abdominal region when compared to controls. There was a trend toward progressive SAT fibrosis of the affected thighs with increasing lipedema stage. Elevated gene expression levels of macrophage markers were found for thigh SAT biopsies, but not in the abdominal region. IHC staining of lipedema thigh biopsies confirmed a transiently elevated macrophage polarization towards an M2-like (anti-inflammatory) phenotype.

Conclusions

In summary, lipedema SAT is associated with stage-dependent adipocyte hypertrophy, stage-progressive interstitial fibrosis and elevated proportion of M2-like macrophages. The character of the inflammatory response differs from primary obesity and may possess an essential role in the development of lipedema.
Challenges and opportunities of molecular epidemiology: using omics to address complex One Health issues in tropical settings
Authors: Tigistu-Sahle Feven , Mekuria Zelalem H. , Satoskar Abhay R. , Sales Gustavo F. C. , Gebreyes Wondwossen A. , Oliveira Celso J. B.
Published: July 2023

The molecular biology tools available since the early 1970s have been crucial to the development of molecular epidemiology as an important branch of public health, and are used for the identification of host genetic and environmental factors associated with both communicable (CDs) and non-communicable diseases (NCDs) across human and animal populations. Molecular epidemiology has significantly contributed to the understanding of etiological agents, disease distribution, and how to track outbreaks, as well as to prevention and control measures against tropical infectious diseases. However, there have been significant limitations compromising the successful application of molecular epidemiology in low-to-middle income countries (LMICs) to address complex issues at the animal–human–environment interface. Recent advances in our capacity to generate information by means of high-throughput DNA genomic sequencing, transcriptomics, and metabolomics have allowed these tools to become accessible at ever-lower costs. Furthermore, recently emerged omics fields such as lipidomics are improving our insights into molecular epidemiology by measuring lipid phenotypes that gauge environmental and genetic factors in large epidemiological studies. In parallel, the development of bioinformatic tools has revolutionized the utility of omics, providing novel perspectives to better characterize pools of biological molecules and translate them into the structure, function, and dynamics of organisms. Unfortunately, the use of such powerful tools has not been optimal for a One Health approach to both CDs and NCDs, particularly in low-resource tropical settings. The aim of this review is to present the fundamentals of omics tools and their potential use in molecular epidemiology, and to critically discuss the impact of omics on the evolving One Health dimension applied to tropical diseases. We use Ethiopia and Brazil as model systems to illustrate existing gaps and opportunities, while also addressing global applications. Moreover, we also discuss perspectives on exploring omics based molecular epidemiology in the context of One Health as a crucial approach to preventing and mitigating the burden of CDs and NCDs at the interface of human health, animal health, and the environment. This review shows that building capacity in the tropical regions is crucial to establishing equitable global health.
Application of Newton iteration to the numerical solution of variable-density groundwater flow in saturated-unsaturated coastal zones
Authors: Yao Meng , Yu Shengchao , Li Hailong
Published: July 2023

When addressing the question of variable saturation and density groundwater flow in coastal zones, the highly nonlinear system of coupled water-salt equations may deserve more attention. The classical Picard scheme is associated with slow calculation speeds and low precision, which hardly meet the actual needs of users. Here, we developed a new numerical solution for coastal groundwater flow issues based on the Newton scheme and compared the advantages and disadvantages of different numerical methods by analyzing the cases of seawater intrusion. The simulation results indicated that the variable-density effect significantly extends the computation time of the model, but the Newton scheme still has the advantages of computational speed and better convergence compared with the Picard scheme, especially in conditions involving high-frequency and large-amplitude tidal fluctuations, steep aquifer slopes, and a coarse grid. Furthermore, the Newton-Picard method, based on the Newton and Picard schemes, improves the robustness of the Newton solution and optimizes the convergence of the Picard solution. This study has revealed the computational characteristics of the Newton scheme in addressing the issues of coastal variable saturation and density groundwater flow, providing new ideas and insights for numerical solutions to coastal groundwater flow problems.
First description of in situ chlorophyll fluorescence signal within East Antarctic coastal polynyas during fall and winter
Authors: Bourreau Lucie , Pauthenet Etienne , Le Ster Loïc , Picard Baptiste , Portela Esther , Sallée Jean-Baptiste , McMahon Clive R. , Harcourt Robert , Hindell Mark , Guinet Christophe , Bestley Sophie , Charrassin Jean-Benoît , DuVivier Alice , Sylvester Zephyr , Krumhardt Kristen , Jenouvrier Stéphanie , Labrousse Sara
Published: July 2023

Antarctic coastal polynyas are persistent and recurrent regions of open water located between the coast and the drifting pack-ice. In spring, they are the first polar areas to be exposed to light, leading to the development of phytoplankton blooms, making polynyas potential ecological hotspots in sea-ice regions. Knowledge on polynya oceanography and ecology during winter is limited due to their inaccessibility. This study describes i) the first in situ chlorophyll fluorescence signal (a proxy for chlorophyll-a concentration and thus presence of phytoplankton) in polynyas between the end of summer and winter, ii) assesses whether the signal persists through time and iii) identifies its main oceanographic drivers. The dataset comprises 698 profiles of fluorescence, temperature and salinity recorded by southern elephant seals in 2011, 2019-2021 in the Cape-Darnley (CDP;67˚S-69˚E) and Shackleton (SP;66˚S-95˚E) polynyas between February and September. A significant fluorescence signal was observed until April in both polynyas. An additional signal occurring at 130m depth in August within CDP may result from in situ growth of phytoplankton due to potential adaptation to low irradiance or remnant chlorophyll-a that was advected into the polynya. The decrease and deepening of the fluorescence signal from February to August was accompanied by the deepening of the mixed layer depth and a cooling and salinification of the water column in both polynyas. Using Principal Component Analysis as an exploratory tool, we highlighted previously unsuspected drivers of the fluorescence signal within polynyas. CDP shows clear differences in biological and environmental conditions depending on topographic features with higher fluorescence in warmer and saltier waters on the shelf compared with the continental slope. In SP, near the ice-shelf, a significant fluorescence signal in April below the mixed layer (around 130m depth), was associated with fresher and warmer waters. We hypothesize that this signal could result from potential ice-shelf melting from warm water intrusions onto the shelf leading to iron supply necessary to fuel phytoplankton growth. This study supports that Antarctic coastal polynyas may have a key role for polar ecosystems as biologically active areas throughout the season within the sea-ice region despite inter and intra-polynya differences in environmental conditions.
Differential activation of neuropeptide FF receptors by gonadotropin-inhibitory hormone peptides in the European sea bass
Authors: Wang Bin , Paullada-Salmerón José A. , Vergès-Castillo Alba , Muñoz-Cueto José A.
Published: July 2023

Neuropeptide FF (NPFF) and gonadotropin-inhibitory hormone (GnIH) are thought to be paralogous, and a recent study has revealed that both NPFF and GnIH peptides can activate the GnIH receptor (GnIHR, also called NPFFR1) in the European sea bass (Dicentrarchus labrax). However, whether GnIH can bind to the NPFF receptor (NPFFR2) is still yet unknown in this species. Accordingly, we further investigated the potential interactions between GnIH and NPFFR2 (two NPFFR2 forms present in sea bass, namely NPFFR2-1 and NPFFR2-2) on the intracellular signaling pathways. Neither GnIH1 nor GnIH2 had any effect on basal CRE-luc activity, while forskolin-stimulated CRE-luc activity was significantly reduced when COS-7 cells expressing sea bass NPFFR2-1 and NPFFR2-2 were challenged with these two GnIH peptides. NPFF and NPAF also inhibited forskolin-induced CRE-luc activity via their cognate receptors. An evident stimulation of SRE-luc activity was observed when COS-7 cells transfected with NPFFR2-1 and NPFFR2-2 were treated with NPFF and NPAF, whereas GnIH peptides had no effect, except a slight but significant increase elicited by 1000 nM of GnIH1 in COS-7 cells expressing NPFFR2-2. Moreover, only GnIH2 exerted an inhibitory action on NFAT-RE-luc activity in COS-7 cells expressing NPFFR2-1. None of GnIH or NPFF peptides altered ERK phosphorylation levels via NPFFR2 receptors. Our results provide new evidence that sea bass GnIH peptides may exert their functions partially via NPFFR2, and PKA, PKC and Ca2+ routes are potential mediators.
Dynamic control of aluminum morphology by wire and arc additive manufacturing based on image feedback
Authors: Wang Xin , liu Linlin , Zhou Chen , Xu Taojin , Luo Maolin , Hu Xiaolin
Published: July 2023

The stability of the forming layer shape is a critical factor that impacts the final quality of sample morphology in wire and arc additive manufacturing (WAAM). This paper investigates the forming process and control methods to identify ways to optimize the process and improve the quality of the final product. The study aims to enhance the quality and precision of samples produced by the WAAM process by establishing a morphology control method based on image feedback. The focus is on real-time image acquisition using a CCD and simultaneous extraction of forming process parameter characteristics. Using a central composite experimental design, a prediction model is developed to estimate key process parameters and feature sizes of deposits, including deposition height and width. To further analyze the dynamic characteristics of feature sizes of deposited layers, step response identification is conducted using three process parameters as the system input: forming speed, arc current, and wire feeding speed. The experiments are designed to determine the weight of each process parameter and achieve a high level of response speed and precision. The findings indicate that the feature size of the deposited layer is most sensitive to changes in forming speed, followed by wire feeding speed, while arc current has the least impact on feature size. After verification, the monitoring of the deposition height and width was found to be in good agreement with the prediction model, with an accuracy of over 90%. The results of this study can be used for size measurement and optimization of large aviation aluminum alloy components using WAAM technology and to improve the quality of products produced using these processes.
A review on experimentally observed mechanical and microstructural characteristics of interfaces in multi-material laser powder bed fusion
Authors: Wu Ziheng , Wilson-Heid Alexander E. , Griffiths R. Joey , Elton Eric S.
Published: July 2023

Additive manufacturing (AM) is a revolutionary technology. One of the key AM categories, metal powder-based fusion processes, has many advantages compared to conventional methods for fabricating structural materials, such as permitting increased geometric complexity. While single material metal powder AM has advanced significantly in the past decade, multi-material AM is gradually attracting more attention owing to the recent breakthrough in multi-material feedstock delivery and the growing interest of fabricating functionally graded components. Multi-material AM offers an alternative route for applications that require location dependent material properties and high geometrical complexity. The AM community has invented several ways to achieve compositional gradients and discrete boundaries in two and three dimensions using mechanical spreading, nozzle-based, electrophotographic, and hybrid techniques. This article reviews the current state of laser powder bed fusion based multi-material AM of metals with focuses on the characteristics of the material interface as well as the properties and performance of the AM built functionally graded materials. We show the common challenges and issues related to material transitions, such as defects, segregation, phase separation, and the efficacy of some potential solutions including material and process optimizations. Additionally, this study evaluates the applicability and limitations of the existing testing standards and methods for measuring mechanical performance of functionally graded materials. Finally, we discuss mechanical testing development opportunities, which can help multi-material AM move towards higher technological maturity. In general, we find that the link between gradient microstructure and mechanical properties is not well understood or studied and suggest several mechanical tests that may better inform this knowledge gap.
Bibliometric and visualized analysis of myopic corneal refractive surgery research: from 1979 to 2022
Authors: Yang Fang , Dong Yi , Bai Chen , Alzogool Mohammad , Wang Yan
Published: July 2023

Background

Myopic corneal refractive surgery is one of the most prevalent ophthalmic procedures for correcting ametropia. This study aimed to perform a bibliometric analysis of research in the field of corneal refractive surgery over the past 40 years in order to describe the current international status and to identify most influential factors, while highlighting research hotspots.

Methods

A bibliometric analysis based on the Web of Science Core Collection (WoSCC) was used to analyze the publication trends in research related to myopic corneal refractive surgery. VOSviewer v.1.6.10 was used to construct the knowledge map in order to visualize the publications, distribution of countries, international collaborations, author productivity, source journals, cited references, keywords, and research hotspots in this field.

Results

A total of 4,680 publications on myopic corneal refractive surgery published between 1979 and 2022 were retrieved. The United States has published the most papers, with Emory University contributing to the most citations. The Journal of Cataract and Refractive Surgery published the greatest number of articles, and the top 10 cited references mainly focused on outcomes and wound healing in refractive surgery. Previous research emphasized “radial keratotomy (RK)” and excimer laser-associated operation methods. The keywords containing femtosecond (FS) laser associated with “small incision lenticule extraction (SMILE)” and its “safety” had higher burst strength, indicating a shift of operation methods and coinciding with the global trends in refractive surgery. The document citation network was clustered into five groups: (1) outcomes of refractive surgery: (2) preoperative examinations for refractive surgery were as follows: (3) complications of myopic corneal refractive surgery; (4) corneal wound healing and cytobiology research related to photorefractive laser keratotomy; and (5) biomechanics of myopic corneal refractive surgery.

Conclusion

The bibliometric analysis in this study may provide scholars with valuable to information and help them better understand the global trends in myopic corneal refractive surgery research frontiers. Two stages of rapid development occurred around 1991 and 2013, shortly after the innovation of PRK and SMILE surgical techniques. The most cited articles mainly focused on corneal wound healing, clinical outcomes, ocular aberration, corneal ectasia, and corneal topography, representing the safety of the new techniques.
Uric acid and glaucoma: a systematic review and meta-analysis
Authors: Mohammadi Mohammad , Yarmohammadi Adeleh , Salehi-Abargouei Amin , Ghasemirad Hamidreza , Shirvani Mohammad , Ghoshouni Hamed
Published: July 2023

Background

Glaucoma, the leading cause of irreversible blindness, is a common disorder that contributes to gradual optic nerve degeneration. The beneficial impacts of uric acid (UA) have been reported in some neurodegenerative conditions such as Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis. But the results of current studies about the association between serum UA level and glaucoma are conflicting. The present meta-analysis was conducted to provide a better understanding of the association between serum UA level and glaucoma.

Methods

We searched the databases of PubMed, Scopus, Web of Science, and Google Scholar systematically until November 20, 2022 to identify case-control studies, comparing the serum UA concentrations of the patients with glaucoma and controls. The mean ± standard division difference was used to assess the difference in serum UA concentrations between the glaucoma patients and controls.

Results

Six studies involving 1,221 glaucoma patients and 1,342 control group were included in the present meta-analysis. This meta-analysis using a random effect model indicated that the mean UA level in glaucoma patients was 0.13 (I2 = 91.92%, 95% CI = −0.42 to 0.68) higher than the controls; however, it was not statistically significant.

Conclusions

Our findings provide evidence that glaucoma patients have a higher serum UA level compared to the controls, but this difference is not statistically significant. Prospective studies are needed to determine the possible association between increased UA and glaucoma pathogenesis.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022364055, identifier: CRD42022364055.
Aerobic methanotrophy increases the net iron reduction in methanogenic lake sediments
Authors: Vigderovich Hanni , Eckert Werner , Elvert Marcus , Gafni Almog , Rubin-Blum Maxim , Bergman Oded , Sivan Orit
Published: July 2023

In methane (CH4) generating sediments, methane oxidation coupled with iron reduction was suggested to be catalyzed by archaea and bacterial methanotrophs of the order Methylococcales. However, the co-existence of these aerobic and anaerobic microbes, the link between the processes, and the oxygen requirement for the bacterial methanotrophs have remained unclear. Here, we show how stimulation of aerobic methane oxidation at an energetically low experimental environment influences net iron reduction, accompanied by distinct microbial community changes and lipid biomarker patterns. We performed incubation experiments (between 30 and 120 days long) with methane generating lake sediments amended with 13C-labeled methane, following the additions of hematite and different oxygen levels in nitrogen headspace, and monitored methane turnover by 13C-DIC measurements. Increasing oxygen exposure (up to 1%) promoted aerobic methanotrophy, considerable net iron reduction, and the increase of microbes, such as Methylomonas, Geobacter, and Desulfuromonas, with the latter two being likely candidates for iron recycling. Amendments of 13C-labeled methanol as a potential substrate for the methanotrophs under hypoxia instead of methane indicate that this substrate primarily fuels methylotrophic methanogenesis, identified by high methane concentrations, strongly positive δ13CDIC values, and archaeal lipid stable isotope data. In contrast, the inhibition of methanogenesis by 2-bromoethanesulfonate (BES) led to increased methanol turnover, as suggested by similar 13C enrichment in DIC and high amounts of newly produced bacterial fatty acids, probably derived from heterotrophic bacteria. Our experiments show a complex link between aerobic methanotrophy and iron reduction, which indicates iron recycling as a survival mechanism for microbes under hypoxia.
Multi-omics analysis of LAMB3 as a potential immunological and biomarker in pan-cancer
Authors: Wang Yanghao , Li Guoyu , Wang ZhiYuan , Wang Weizhou , Wang Xiaofang , Luo Xuan , Zhao Juan , Li Fangfang , Bian Li
Published: July 2023

Laminin Subunit Beta 3 (LAMB3) is a transcription factor and participates in the coding of laminin. It plays an important role in cell proliferation, adhesion, and transfer by regulating various target genes and signaling pathways. However, the role of LAMB3 in human pan-cancer immunology and prognosis is still poorly understood. The TCGA, GTEx, CCLE, and HPA databases were utilized for the analysis of LAMB mRNA and protein expression. The expression of LAMB3 in various immune and molecular subtypes of human cancer was examined using the TISIDB database. The prognostic significance of LAMB3 in various cancers and clinical subtypes was investigated using Kaplan-Meier and Cox regression analysis. The relationship between LAMB3 expression, various immune cell infiltration, immune checkpoints, tumor mutational load, microsatellite instability, and DNA methylation was examined using the TCGA database. Clinical samples of four lung cancer cell lines and eight lung cancer cases were collected to confirm the expression of mRNA in lung cancer. In 17 cancers, the mRNA for LAMB3 is expressed differently and has good diagnostic and prognostic value in 22 cancers. Cox regression and Nomogram analysis show that LAMB3 is an independent risk factor for 15 cancers. LAMB3 is implicated in a variety of tumorigenesis and immune-related signaling pathways, according to GO, KEGG, and GSEA results. LAMB3 expression was associated with TMB in 33 cancer types and MSI in 32 cancer types, while in lung cancer LAMB3 expression was strongly associated with immune cell infiltration and negatively correlated with all seven methylated CpG islands. Cellular experiments demonstrated that LAMB3 promotes malignant behavior of tumor cells. Preliminary mechanistic exploration revealed its close association with PD-L1, CTLA4, cell stemness gene CD133 and β-catenin-related signaling pathways. Based on these findings, it appears that LAMB3 could be a potential therapeutic target for immunotherapy and tumor prognosis. Our findings reveal an important role for LAMB3 in different cancer types.
SPARC: a potential target for functional nanomaterials and drugs
Authors: Jiang Shan , Sun Hui-Feng , Li Shuang , Zhang Ning , Chen Ji-Song , Liu Jian-Xin
Published: July 2023

Secreted protein acidic and rich in cysteine (SPARC), also termed osteonectin or BM-40, is a matricellular protein which regulates cell adhesion, extracellular matrix production, growth factor activity, and cell cycle. Although SPARC does not perform a structural function, it, however, modulates interactions between cells and the surrounding extracellular matrix due to its anti-proliferative and anti-adhesion properties. The overexpression of SPARC at sites, including injury, regeneration, obesity, cancer, and inflammation, reveals its application as a prospective target and therapeutic indicator in the treatment and assessment of disease. This article comprehensively summarizes the mechanism of SPARC overexpression in inflammation and tumors as well as the latest research progress of functional nanomaterials in the therapy of rheumatoid arthritis and tumors by manipulating SPARC as a new target. This article provides ideas for using functional nanomaterials to treat inflammatory diseases through the SPARC target. The purpose of this article is to provide a reference for ongoing disease research based on SPARC-targeted therapy.
Virtual brain simulations reveal network-specific parameters in neurodegenerative dementias
Authors: Monteverdi Anita , Palesi Fulvia , Schirner Michael , Argentino Francesca , Merante Mariateresa , Redolfi Alberto , Conca Francesca , Mazzocchi Laura , Cappa Stefano F. , Cotta Ramusino Matteo , Costa Alfredo , Pichiecchio Anna , Farina Lisa M. , Jirsa Viktor , Ritter Petra , Gandini Wheeler-Kingshott Claudia A. M. , D’Angelo Egidio
Published: July 2023

Introduction

Neural circuit alterations lay at the core of brain physiopathology, and yet are hard to unveil in living subjects. The Virtual Brain (TVB) modeling, by exploiting structural and functional magnetic resonance imaging (MRI), yields mesoscopic parameters of connectivity and synaptic transmission.

Methods

We used TVB to simulate brain networks, which are key for human brain function, in Alzheimer’s disease (AD) and frontotemporal dementia (FTD) patients, whose connectivity and synaptic parameters remain largely unknown; we then compared them to healthy controls, to reveal novel in vivo pathological hallmarks.

Results

The pattern of simulated parameter differed between AD and FTD, shedding light on disease-specific alterations in brain networks. Individual subjects displayed subtle differences in network parameter patterns that significantly correlated with their individual neuropsychological, clinical, and pharmacological profiles.

Discussion

These TVB simulations, by informing about a new personalized set of networks parameters, open new perspectives for understanding dementias mechanisms and design personalized therapeutic approaches.
The cerebellum and cognitive neural networks
Authors: Zhang Pingshu , Duan Liqin , Ou Ya , Ling Qirong , Cao Lingyun , Qian Hongchun , Zhang Jian , Wang Jing , Yuan Xiaodong
Published: July 2023

Cognitive function represents a complex neurophysiological capacity of the human brain, encompassing a higher level of neural processing and integration. It is widely acknowledged that the cerebrum plays a commanding role in the regulation of cognitive functions. However, the specific role of the cerebellum in cognitive processes has become a subject of considerable scholarly intrigue. In 1998, Schmahmann first proposed the concept of “cognitive affective syndrome (CCAS),” linking cerebellar damage to cognitive and emotional impairments. Since then, a substantial body of literature has emerged, exploring the role of the cerebellum in cognitive neurological function. The cerebellum’s adjacency to the cerebral cortex, brainstem, and spinal cord suggests that the cerebral-cerebellar network loops play a crucial role in the cerebellum’s participation in cognitive neurological functions. In this review, we comprehensively examine the recent literature on the involvement of the cerebellum in cognitive functions from three perspectives: the cytological basis of the cerebellum and its anatomical functions, the cerebellum and cognitive functions, and Crossed cerebellar diaschisis. Our aim is to shed light on the role and mechanisms of the cerebellum in cognitive neurobrain networks.
Abnormal brain activity in lumbar disc herniation patients with chronic pain is associated with their clinical symptoms
Authors: Tang Cheng , Guo Guangxin , Fang Sitong , Yao Chongjie , Zhu Bowen , Kong Lingjun , Pan Xuanjin , Li Xinrong , He Weibin , Wu Zhiwei , Fang Min
Published: July 2023

Introduction

Lumbar disc herniation, a chronic degenerative disease, is one of the major contributors to chronic low back pain and disability. Although many studies have been conducted in the past on brain function in chronic low back pain, most of these studies did not classify chronic low back pain (cLBP) patients according to their etiology. The lack of etiologic classification may lead to inconsistencies between findings, and the correlation between differences in brain activation and clinical symptoms in patients with cLBP was less studied in the past.

Methods

In this study, 36 lumbar disc herniation patients with chronic low back pain (LDHCP) and 36 healthy controls (HCs) were included to study brain activity abnormalities in LDHCP. Visual analogue scale (VAS), oswestry disability index (ODI), self-rating anxiety scale (SAS), self-rating depression scale (SDS) were used to assess clinical symptoms.

Results

The results showed that LDHCP patients exhibited abnormally increased and diminished activation of brain regions compared to HCs. Correlation analysis showed that the amplitude of low frequency fluctuations (ALFF) in the left middle frontal gyrus is negatively correlated with SAS and VAS, while the right superior temporal gyrus is positively correlated with SAS and VAS, the dorsolateral left superior frontal gyrus and the right middle frontal gyrus are negatively correlated with VAS and SAS, respectively.

Conclusion

LDHCP patients have brain regions with abnormally increased and abnormally decreased activation compared to healthy controls. Furthermore, some of the abnormally activated brain regions were correlated with clinical pain or emotional symptoms.
Maternal dietary fiber intake during pregnancy and child development: the Japan Environment and Children's Study
Authors: Miyake Kunio , Horiuchi Sayaka , Shinohara Ryoji , Kushima Megumi , Otawa Sanae , Yui Hideki , Akiyama Yuka , Ooka Tadao , Kojima Reiji , Yokomichi Hiroshi , Mochizuki Kazuki , Yamagata Zentaro ,   The Japan Environment Children's Study Group
Published: July 2023

Background

Animal studies have shown that maternal low-fiber diets during pregnancy may impair brain development and function in offspring, but this has not been validated by epidemiological studies. The aim of this study was to investigate the link between maternal dietary fiber intake during pregnancy and neurodevelopmental delay in offspring using a large birth cohort.

Methods

A total of 76,207 mother-infant pairs were analyzed using data from the Japan Environment and Children's Study, a nationwide prospective cohort study. Maternal dietary fiber intake was estimated using the food frequency questionnaire in mid-pregnancy. Maternal dietary fiber intake was adjusted for energy and classified into quintiles. Developmental delay was assessed in five domains using the Japanese version of the Ages and Stages Questionnaire, Third Edition at the age of 3 years. The logistic regression analysis was performed to estimate the odds ratio (OR) and 95% confidence interval (CI) for the link between dietary fiber intake during pregnancy and developmental delay at the age of 3 years.

Results

The lowest intake group of total dietary fiber had a higher risk of delayed communication [adjusted OR (aOR), 1.51; 95% CI, 1.32–1.74], fine motor (aOR, 1.45; 95% CI, 1.32–1.61), problem-solving (aOR, 1.46; 95% CI, 1.32–1.61), and personal-social skills (aOR, 1.30; 95% CI, 1.12–1.50) than did the highest intake group. An analysis that excluded the effects of insufficient folic acid intake during pregnancy also showed a similar trend.

Conclusion

This study showed that maternal dietary fiber deficiency during pregnancy might influence an increased risk of neurodevelopmental delay in offspring.
Effects of high oleic acid peanuts on mice’s liver and adipose tissue metabolic parameters and gut microbiota composition
Authors: Anavi-Cohen Sarit , Tsybina-Shimshilashvili Nina , Zandani Gil , Hovav Ran , Sela Noa , Nyska Abraham , Madar Zecharia
Published: July 2023

This study aimed to investigate the effects of two types of peanuts, regular Hanoch (HN) and a new high-oleic cultivar., Hanoch-Oleic (HO), on metabolic parameters and gut microbiota composition. Male C57BL/6 mice were fed with a normal diet (ND) or ND supplemented with HN (NDh) or HO (NDo). Following 18 weeks of diet regimen, the NDo group exhibited reduced body weight and peri-gonadal adipose-to-body weight ratio, paralleled to lesser food consumption. Although blood levels of total cholesterol, HDL-cholesterol, free fatty acids, and liver enzyme levels did not differ between groups, decreased insulin sensitivity was found in the NDh group. Within adipose tissue, the expression of lipolytic and lipogenic enzymes was higher, while those related to lipid oxidation were lower in the NDh group compared to the NDo group. Additionally, HO peanuts consumption promoted the establishment of a healthy microbiota, with an enhanced abundance of Bifidobacterium, Lactobacillus, and Coprococcus genera. In conclusion, the inclusion of the HO peanut cultivar., rather than the conventional peanut cultivar., in a balanced diet was related to better metabolic outcomes and was linked to a favorable microbiota profile.
Apolipoprotein A-I attenuates peritoneal fibrosis associated with peritoneal dialysis by inhibiting oxidative stress and inflammation
Authors: Lu Jing , Gao Jie , Sun Jing , Wang Haiping , Sun Huijuan , Huang Qian , Zhang Yao , Zhong Shuo
Published: July 2023

Apolipoprotein A-I (apoA-I), 90% of which is present in high-density lipoprotein (HDL), is the main constituent of HDL, has anti-inflammatory and anti-oxidant properties, and has received extensive attention in anti-atherosclerosis. Yet little is known about apoA-I ’s role in peritoneal dialysis. In this study, by analyzing PD patients (n = 81), we found that decreased apoA/HDL-C ratio is significantly associated with rapid decline in peritoneal function. Further studies were performed in animal experiments to determine the ascendancy of apolipoprotein A-I mimetic peptide (D-4F) on peritoneum, we found that D-4F administration reduced peritoneal fibrosis and peritoneal endothelial mesenchymal transformation (EMT) induced by high glucose peritoneal dialysate, such as N-cadherin, Fibronectin, Vimentin, and α-smooth muscle actin (α-SMA) expression decreased. In mechanism, D-4F can significantly inhibit Smad2/3 phosphorylation, which is the major pathway leading to fibrosis. Furthermore, D-4F treatment inhibited NADPH oxidase and thiobarbituric acid reactive substances (TBARS) expression, increased the activity of certain enzymes, such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Finally, treatment with D-4F inhibits the expression of interleukins-6(IL-6), Interleukin-1β(IL-1β), and tumor necrosis factor-α(TNF-α). Taken together, based on the above research evidence, apoA-I and its peptide mimic may regulate the oxidative stress, TGF- β1/Smads signaling pathway and inflammatory response to reduce peritoneal fibrosis due to peritoneal dialysis.
A review of FDA approved drugs and their formulations for the treatment of breast cancer
Authors: Chaurasia Mohini , Singh Romi , Sur Srija , Flora S. J. S.
Published: July 2023

Breast cancer is one of the most diagnosed solid cancers globally. Extensive research has been going on for decades to meet the challenges of treating solid tumors with selective compounds. This article aims to summarize the therapeutic agents which are either being used or are currently under approval for use in the treatment or mitigation of breast cancer by the US FDA, to date. A structured search of bibliographic databases for previously published peer-reviewed research papers on registered molecules was explored and data was sorted in terms of various categories of drugs used in first line/adjuvant therapy for different stages of breast cancer. We included more than 300 peer-reviewed papers, including both research and reviews articles, in order to provide readers an useful comprehensive information. A list of 39 drugs are discussed along with their current status, dose protocols, mechanism of action, pharmacokinetics, possible side effects, and marketed formulations. Another interesting aspect of the article included focusing on novel formulations of these drugs which are currently in clinical trials or in the process of approval. This exhaustive review thus shall be a one-stop solution for researchers who are working in the areas of formulation development for these drugs.
Telmisartan versus metformin in downregulating myostatin gene expression and enhancing insulin sensitivity in the skeletal muscles of type 2 diabetic rat model
Authors: Abd-Eltawab Tammam Ahmed , Rizg Waleed Y. , Fakhry Boushra Amy , Alhelf Maha , Alissa Mohammed , Soliman Ghada F. , Nady Ouais Ghada , Hosny Khaled M. , Alkhalidi Hala M. , Elebiary Ahmed Magdy
Published: July 2023

Objective: Telmisartan is an angiotensin receptor blocker (ARB) that specifically blocks angiotensin II type-1 receptors (AT1R). Telmisartan has been proven to have antidiabetic effects via a variety of mechanisms, and it can be utilized in some diabetic patients due to its dual benefit for hypertensive patients with type 2 DM (T2DM) and when the other oral antidiabetic medications are intolerable or contraindicated. However, its precise underlying hypoglycemic mechanism is still obscure.

Aim of work: We sought to establish a link between telmisartan administration and myostatin expression in skeletal muscles of T2DM rat model as a potential hypoglycemic mechanism of telmisartan.

Materials and Methods: 32 male albino rats were included in the study; 8 rats served as controls (group I). T2DM was inducted in the other 24 rats, which were then randomly subdivided into 3 groups (8 in each): (group II) the Diabetic group and (groups III and IV) which were treated with either telmisartan (8 mg/kg/day) or metformin (250 mg/kg/day) respectively via oral gavage for a 4-week period.

Results: Telmisartan administration resulted in a significant improvement in OGTT, HOMA-IR, glucose uptake, and muscle mass/body ratios in Telmisartan group as compared to Diabetic group (p < 0.05). Additionally, telmisartan induced a significant boost in adiponectin and IL-10 serum levels with a substantial drop in TNF-α and IL-6 levels in Telmisartan group compared to diabetic rats (p < 0.05). Moreover, telmisartan significantly boosted SOD and GSH, and decreased MDA levels in the skeletal muscles of telmisartan group. Furthermore, a significant downregulation of myostatin and upregulation of insulin receptor, IRS-1, and IRS-3 genes in the skeletal muscles of Telmisartan group were also detected. Histologically, telmisartan attenuated the morphological damage in the skeletal muscle fibers compared to diabetic rats, as evidenced by a considerable decrease in the collagen deposition area percentage and a reduction in NF-kB expression in the muscle tissues of group III.

Conclusion: Telmisartan administration dramatically reduced myostatin and NF-kB expressions in skeletal muscles, which improved insulin resistance and glucose uptake in these muscles, highlighting a novel antidiabetic mechanism of telmisartan in treating T2DM.
Effects of linalyl acetate on oxidative stress, inflammation and endothelial dysfunction: can linalyl acetate prevent mild cognitive impairment?
Authors: Shin You Kyoung , Seol Geun Hee
Published: July 2023

Mild cognitive impairment (MCI) is a major public health challenge with an increasing prevalence. Although the mechanisms underlying the development of MCI remain unclear, MCI has been reported to be associated with oxidative stress, inflammatory responses, and endothelial dysfunction, suggesting that agents that reduce these factors may be key to preventing MCI. Currently, no agents have been approved for the treatment of MCI, with the efficacy of commonly prescribed cholinesterase inhibitors remaining unclear. Relatively safe natural products that can prevent the development of MCI are of great interest. Linalyl acetate (LA), the major component of clary sage and lavender essential oils, has been shown to have a variety of pharmacological effects, including anti-hypertensive, anti-diabetic, neuroprotective, anti-inflammatory, and antioxidant properties, which may have the potential for the prevention of MCI. The present review briefly summarizes the pathogenesis of MCI related to oxidative stress, inflammatory responses, and endothelial dysfunction as well as the benefits of LA against these MCI-associated factors. The PubMed and Google Scholar databases were used to search the relevant literature. Further clinical research may lead to the development of new strategies for preventing MCI, particularly in high-risk populations with oxidative stress, inflammatory responses, and endothelial dysfunction (e.g., patients with hypertension and/or diabetes mellitus).
Feasibility study of nuclear excitation by electron capture using an electron beam ion trap
Authors: Wang Yumiao , Ma Zhiguo , Yang Yi , Fu Changbo , He Wanbing , Ma Yugang
Published: July 2023

The nuclear excitation by electron capture (NEEC) mechanism is considered to be one of the most effective ways to excite nuclear isomers. Despite being proposed over 50 years ago, direct experimental evidence of NEEC is yet elusive. In this study, we propose an experimental scheme to examine the NEEC process using an electron beam ion trap (EBIT). In an EBIT, highly charged ions are bombarded by an electron beam, which can result in excitation of the nuclei in the trap through mechanisms such as NEEC and Coulomb excitation (CE), etc. Our calculations show that the total rates of NEEC production for some nuclei can reach over 0.1/s, which is higher than these from other mechanisms like CE. The proposed scheme may result in the confirmation of the existence of NEEC, and can also be used to study atomic nuclear excitation related processes.
Strong polarization-controlled terahertz generation by bi-elliptical polarized laser fields
Authors: Liu Yan-Mei , Li Ya-Ning , Zhang Lei , Jiao Zhi-Hong , Zhao Song-Feng , Wang Guo-Li
Published: July 2023

Terahertz generation from atoms driven by two color linearly polarized (LP) and circularly polarized (CP) laser fields have been well investigated. In this work, based on the photocurrent model, we investigate theoretically the intensity and polarization characteristics of terahertz waves radiated by the bi-elliptical polarized two-color laser fields with orthogonal or parallel major axes. We show that polarization-controlled, including circularly polarized terahertz waves with sufficient intensity comparable to that of co-rotating CP or parallel LP laser field, can be generated by using a longer-wavelength few-cycle bi-elliptical field. Our simulations also show that THz energy and ellipticity can be dramatically improved with dual-color elliptical field with tiny or large ellipticity, compared with that with two-color orthogonal LP field and counter-rotating CP laser field, respectively. Bi-elliptical polarized laser field provides a huge parameter space allowing for far-reaching control of THz emission.