bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of potential ferroptosis-associated biomarkers in rheumatoid arthritis
Authors: He Xu , Zhang Juqi , Gong Mingli , Gu Yanlun , Dong Bingqi , Pang Xiaocong , Zhang Chenglong , Cui Yimin
Published: July 2023

Background

Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by inflammation and gradual joint degeneration, resulting in function disability. Recently, ferroptosis, a novel form of regulated cell death that involves iron-dependent lipid peroxidation, has been implicated in the pathogenesis of RA. However, the underlying molecular mechanisms and key genes involved in ferroptosis in RA remain largely unknown.

Methods

The GSE134420 and GSE77298 datasets were downloaded and DEGs were identified using R software. The DEGs were then mapped to the dataset of 619 ferroptosis-related genes obtained from the GeneCards database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted to investigate the possible biological functions. Protein-protein interaction (PPI) networks were constructed to identify the hub genes. The relationship between hub genes and immune infiltration was estimated using the CIBERSORT algorithms. Gene Set Enrichment Analysis (GSEA) was used to explore the underlying signaling pathways of hub genes. Genome-wide association studies (GWAS) analysis was performed to confirm the pathogenic regions of the hub genes. RcisTarget and Gene-motif ranking databases were used to identify transcription factors (TFs) associated with the hub genes. The miRcode databases were utilized to construct the microRNA (miRNA)-messenger RNA (mRNA) network. Single-cell analysis was utilized to cluster cells and display the expression of hub genes in cell clusters. Finally, the expression and potential mechanism of hub genes were investigated in human and experimental samples.

Results

Three hub genes PTGS2, ENO1, and GRN highly associated with ferroptosis were identified. Four pathogenic genes HLA-B, MIF, PSTPIP, TLR1 were identified that were significantly and positively correlated with the expression levels of hub genes. The results of the GSEA showed that the hub genes were significantly enriched in pathways related to immunity, lysosome, phagocytosis and infection. ENO1 and PTGS2 were enriched in the TF-binding motif of cisbp_M5493. The hub genes were validated in experimental and patient samples and highly level of ENO1 expression was found to inhibit ACO1, which reduces ferroptosis in proliferating fibroblast-like synoviocytes (FLS).

Conclusion

PTGS2, ENO1 and GRN were identified and validated as potential ferroptosis-related biomarkers. Our work first revealed that ENO1 is highly expressed in RA synovium and that ferroptosis may be regulated by the ENO1-ACO1 axis, advancing the understanding of the underlying ferroptosis-related mechanisms of synovial proliferation and providing potential diagnostic and therapeutic targets for RA.
Immune escape and resistance to immunotherapy in mismatch repair deficient tumors
Authors: Mestrallet Guillaume , Brown Matthew , Bozkus Cansu Cimen , Bhardwaj Nina
Published: July 2023

Up to 30% of colorectal, endometrial and gastric cancers have a deficiency in mismatch repair (MMR) protein expression due to either germline or epigenetic inactivation. Patients with Lynch Syndrome who inherit an inactive MMR allele have an up to 80% risk for developing a mismatch repair deficient (MMRd) cancer. Due to an inability to repair DNA, MMRd tumors present with genomic instability in microsatellite regions (MS). Tumors with high MS instability (MSI-H) are characterized by an increased frequency of insertion/deletions (indels) that can encode novel neoantigens if they occur in coding regions. The high tumor antigen burden for MMRd cancers is accompanied by an inflamed tumor microenvironment (TME) that contributes to the clinical effectiveness of anti-PD-1 therapy in this patient population. However, between 40 and 70% of MMRd cancer patients do not respond to treatment with PD-1 blockade, suggesting that tumor-intrinsic and -extrinsic resistance mechanisms may affect the success of checkpoint blockade. Immune evasion mechanisms that occur during early tumorigenesis and persist through cancer development may provide a window into resistance pathways that limit the effectiveness of anti-PD-1 therapy. Here, we review the mechanisms of immune escape in MMRd tumors during development and checkpoint blockade treatment, including T cell dysregulation and myeloid cell-mediated immunosuppression in the TME. Finally, we discuss the development of new therapeutic approaches to tackle resistance in MMRd tumors, including cancer vaccines, therapies targeting immunosuppressive myeloid programs, and immune checkpoint combination strategies.
Dynamics of rhizosphere bacterial communities and soil physiochemical properties in response to consecutive ratooning of sugarcane
Authors: Khan Abdullah , Wei Yibin , Adnan Muhammad , Ali Izhar , Zhang Muqing
Published: July 2023

Ratooning in sugarcane often leads to soil problems such as degradation, acidification, and soil-borne diseases that negatively impact agriculture output and sustainability. Understanding the alteration in bacterial communities, activities, and their diversity connected to the plant and soil under consecutive ratooning still needs to be clarified. To address this gap, multidisciplinary approaches such as Illumina sequencing and measurement of soil nutrients and enzymes were used in this study to analyze soil samples in a field with three consecutive ratooning sugarcane crops. The results revealed a decline in crop yield and significant changes (P < 0.05) in soil nutrients and bacterial diversity. Ratooning resulted in an acidic environment that potentially affected soil nutrients and enzyme activity responsible for the cycling of carbon, nitrogen, and phosphorous. Non-metric dimensional scaling (NMDS) confirmed the effect of ratooning on soil attributes. Moreover, a positive correlation between soil physiochemical properties and soil enzymes was observed. Alpha diversity indices indicated greater bacterial diversity in ratooning sugarcane. Bacterial diversity varied throughout the ratooning crop, and significant (P < 0.05) changes in the relative abundance of specific phyla were observed. For example, the relative abundance of Proteobacteria was decreased, and Acidobacteria was increased. Furthermore, the relative abundance of bacterial phyla was strongly correlated with soil attributes (enzymes and nutrients). Additionally, ratooning results in the depletion or enrichment of important agriculture microbial genera such as Sphingomonas, Burkholderia, and Acidothermus (P < 0.05), respectively. In conclusion, ratooning led to soil acidification, decreased fertility, and altered microbial structure and activity. Thus, restraining soil acidity by means of liming or biofertilizers to maintain soil nutrients, enzymatic activities, and microbial structure could benefit plants and soil to help create a long-term eco-friendly sugarcane cropping system.
Rasch validation of a new scale to measure dependency in arm use in daily life: the Upper Limb Lucerne ICF-based Multidisciplinary Observation Scale
Authors: Van de Winckel Ann , Ottiger Beatrice , Veerbeek Janne Marieke , Nyffeler Thomas , Vanbellingen Tim
Published: July 2023

Introduction

About 77% of adults with stroke have upper limb impairments. Many scales are available to measure the impairment and activity level of the affected limb. However, an observational scale to assess dependency on others in upper limb performance during daily life activities instead of laboratory settings is lacking. Therefore, we developed a new 5-item Upper Limb Lucerne ICF-based Multidisciplinary Observation Scale (UL-LIMOS). As next step in the psychometric analysis, we evaluated the unidimensionality and structural validity of the UL-LIMOS with Rasch Measurement Theory and we calculated a cut-off score for independent arm use in daily life activities at discharge.

Methods

This is a single-center cross-sectional study in adults with (sub) acute stroke. We applied Rasch Measurement Theory (RMT) to analyze the structural validation and unidimensionality of the UL-LIMOS. The outputs provide evidence of unidimensionality, item and person fit, overall fit, differential item functioning (DIF), principal component analysis of residuals (PCAR), person separation reliability (PSR), and residual item correlations (to identify local item dependence). Person mean location, floor and ceiling effects identify proper targeting.

Results

We recruited 407 adults with (sub) acute stroke (median age 63 years, 157 women). All items and persons fit the Rasch model. The PSR of 0.90 indicates that clinicians and researchers can reliably use the scale for individual decision-making. There were small floor (2.70%) and ceiling (13.00%) effects. The average person mean location was 1.32 ± 2.99 logits. There was no DIF. PCAR eigenvalue was 2.46 with 49.23% explained variance. Paired t-tests revealed that 0.89% of person locations were significantly different, confirming unidimensionality. One pair of items (arm and hand use and fine hand use) showed residual item correlations. The ROC’s AUC was 0.90, CI95% = [0.85–0.96] with cut-off score of ≥14/20, and high sensitivity (87%, CI95% = [81%–91%]), specificity (83%, CI95% = [77%–87%]) for independent arm use in daily living at discharge.

Discussion

The new Rasch-based UL-LIMOS is a valid ICF-based observation performance scale at the ICF-activity level, to evaluate dependency during upper limb use in daily life in adults with stroke. Additional psychometric analyses are warranted. The UL-LIMOS would be a valuable addition to the core assessments of adults with (sub) acute stroke.
Mechanism of PGC-1α-mediated mitochondrial biogenesis in cerebral ischemia–reperfusion injury
Authors: Yuan Ying , Tian Yuan , Jiang Hui , Cai Luo-yang , Song Jie , Peng Rui , Zhang Xiao-ming
Published: July 2023

Cerebral ischemia–reperfusion injury (CIRI) is a series of cascade reactions that occur after blood flow recanalization in the ischemic zone in patients with cerebral infarction, causing an imbalance in intracellular homeostasis through multiple pathologies such as increased oxygen free radicals, inflammatory response, calcium overload, and impaired energy metabolism, leading to mitochondrial dysfunction and ultimately apoptosis. Rescue of reversibly damaged neurons in the ischemic hemispheric zone is the key to saving brain infarction and reducing neurological deficits. Complex and active neurological functions are highly dependent on an adequate energy supply from mitochondria. Mitochondrial biogenesis (MB), a process that generates new functional mitochondria and restores normal mitochondrial function by replacing damaged mitochondria, is a major mechanism for maintaining intra-mitochondrial homeostasis and is involved in mitochondrial quality control to ameliorate mitochondrial dysfunction and thus protects against CIRI. The main regulator of MB is peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), which improves mitochondrial function to protect against CIRI by activating its downstream nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (TFAM) to promote mitochondrial genome replication and transcription. This paper provides a theoretical reference for the treatment of neurological impairment caused by CIRI by discussing the mechanisms of mitochondrial biogenesis during cerebral ischemia–reperfusion injury.
Multiple micronutrient deficiencies alter energy metabolism in host and gut microbiome in an early-life murine model
Authors: Littlejohn Paula T. , Bar-Yoseph Haggai , Edwards Karlie , Li Hong , Ramirez-Contreras Cynthia Y. , Holani Ravi , Metcalfe-Roach Avril , Fan Yiyun M. , Yang Tom Min-Shih , Radisavljevic Nina , Hu Xiaoke , Johnson James D. , Finlay B. Brett
Published: July 2023

Introduction

Micronutrients perform a wide range of physiological functions essential for growth and development. However, most people still need to meet the estimated average requirement worldwide. Globally, 2 billion people suffer from micronutrient deficiency, most of which are co-occurring deficiencies in children under age five. Despite decades of research, animal models studying multiple micronutrient deficiencies within the early-life period are lacking, which hinders our complete understanding of the long-term health implications and may contribute to the inefficacy of some nutritional interventions. Evidence supporting the Developmental Origins of Health and Disease (DOHaD) theory demonstrates that early-life nutritional deficiencies carry life-long consequences mediated through various mechanisms such as abnormal metabolic programming, stunting, altered body composition, and the gut microbiome. However, this is largely unexplored in the multiple micronutrient deficient host.

Methods

we developed a preclinical model to examine undernutrition’s metabolic and functional impact on the host and gut microbiome early in life. Three-week-old weanling C57BL/6N male mice were fed a low-micronutrient diet deficient in zinc, folate, iron, vitamin A, and vitamin B12 or a control diet for 4-weeks.

Results

Our results showed that early-life multiple micronutrient deficiencies induced stunting, altered body composition, impaired glucose and insulin tolerance, and altered the levels of other micronutrients not depleted in the diet within the host. In addition, functional metagenomics profiling and a carbohydrate fermentation assay showed an increased microbial preference for simple sugars rather than complex ones, suggestive of a less developed microbiome in the low-micronutrient-fed mice. Moreover, we found that a zinc-only deficient diet was not sufficient to induce these phenotypes, further supporting the importance of studying co-occurring deficiencies.

Discussion

Together, these findings highlight a previously unappreciated role of early-life multiple micronutrient deficiencies in shaping the metabolic phenome of the host and gut microbiome through altered glucose energy metabolism, which may have implications for metabolic disease later in life in micronutrient-deficient survivors.
The impact of high-glucose or high-fat diets on the metabolomic profiling of mice
Authors: Xie Dadi , Zhang Yanbo , Guo Yujin , Xue Xianzhong , Zhao Shiyuan , Geng Chunmei , Li Yuanyuan , Yang Rui , Gan Yizhang , Li Hanbing , Ren Zhongfa , Jiang Pei
Published: July 2023

Objective

Diets high in glucose or fat contribute to an increased prevalence of the diseases. Therefore, the objective of the current research was to observe and evaluate the impact of dietary components on different metabolomic profiles in primary tissues of mice.

Methods

For 8 weeks, diet with high-glucose or-fat was given to C57BL/6 J mice. The levels of metabolites in the primary tissues of mice were studied using gas chromatography-mass spectrometry (GC-MS) and analyzed using multivariate statistics.

Results

By comparing the metabolic profiles between the two diet groups and control group in mice main tissues, our study revealed 32 metabolites in the high-glucose diet (HGD) group and 28 metabolites in the high-fat diet (HFD) group. The most significantly altered metabolites were amino acids (AAs; L-alanine, L-valine, glycine, L-aspartic acid, L-isoleucine, L-leucine, L-threonine, L-glutamic acid, phenylalanine, tyrosine, serine, proline, and lysine), fatty acids (FAs; propanoic acid, 9,12-octadecadienoic acid, pentadecanoic acid, hexanoic acid, and myristic acid), and organic compounds (succinic acid, malic acid, citric acid, L-(+)-lactic acid, myo-inositol, and urea). These metabolites are implicated in many metabolic pathways related to energy, AAs, and lipids metabolism.

Conclusion

We systematically analyzed the metabolic changes underlying high-glucose or high-fat diet. The two divergent diets induced patent changes in AA and lipid metabolism in the main tissues, and helped identify metabolic pathways in a mouse model.
Advances in nutritional supplementation for sarcopenia management
Authors: Liu Simin , Zhang Lin , Li Shuangqing
Published: July 2023

Sarcopenia is a syndrome characterized by a decline in muscular mass, strength, and function with advancing age. The risk of falls, fragility, hospitalization, and death is considerably increased in the senior population due to sarcopenia. Although there is no conclusive evidence for drug treatment, resistance training has been unanimously recognized as a first-line treatment for managing sarcopenia, and numerous studies have also pointed to the combination of nutritional supplementation and resistance training as a more effective intervention to improve quality of life for people with sarcopenia. People with both malnutrition and sarcopenia have a higher mortality rate, so identifying people at risk of malnutrition and intervening early is extremely important to avoid sarcopenia and its associated problems. This article provides important information for dietary interventions in sarcopenia by summarizing the discoveries and developments of nutritional supplements such as protein, leucine, β-hydroxy-β-methylbutyric acid, vitamin D, vitamin C, vitamin E, omega-3 fatty acids, creatine, inorganic nitrate, probiotics, minerals, collagen peptides, and polyphenols in the management of sarcopenia.
Comparison of primary hepatic neuroendocrine tumors and non-hepatitis B non-hepatitis C hepatocellular carcinoma on contrast-enhanced ultrasound
Authors: Tan Zhizhi , Li Jiawu , Wu Zhenru , Zhou Zhengling , Yang Lulu , Luo Yan
Published: July 2023

Objective

The purpose of this study was to compare the sonographic features of primary hepatic neuroendocrine tumors (PHNETs) to those of non-hepatitis B and non-hepatitis C hepatocellular carcinoma (NBNC-HCC) on contrast-enhanced ultrasound (CEUS).

Materials and methods

Fourteen patients with a mean age of 56.9 ± 12.2 (SD) years with histopathologically confirmed PHNET were included in the study. Twenty-eight patients with a mean age of 58.5 ± 10.4 years with histopathologically confirmed NBNC-HCC were randomly selected as the control group. The clinical data, conventional ultrasound and CEUS features were retrospectively analyzed between PHNET and NBNC-HCC.

Results

PHNET was more common in women (57.1%, 8/14 cases), and NBNC-HCC was more common in men (75.0%, 21/28) (P=0.040). No significant differences were observed in etiology, tumor marker, and liver function between the two group (P>0.05). Conventional ultrasound revealed that the tumor size of PHNET (10.1 ± 4.7 cm) was larger than that of NBNC-HCC (5.9 ± 3.8 cm) (P=0.006). NBNC-HCC was predominantly hypoechoic, while the echogenicity of PHNET varied (P=0.001). On CEUS, 57.1% (8/14) of PHNETs showed heterogeneous hyperenhancement, whereas 77.0% (21/28) of NBNC-HCC presented homogeneous hyperenhancement (P=0.015). Furthermore, 35.7% (5/14) of PHNETs showed early washout (onset of washout <60 s), which was significantly different from that of NBNC-HCC (3.7%, 1/28) (P=0.005).

Conclusion

CEUS is helpful in discriminating between PHNET and NBNC-HCC. PHNETs mainly present as a single mass with a large size (>10 cm) in the liver. The CEUS showed that most PHNETs exhibited heterogeneous enhancement in the arterial phase, washout in the portal venous and late phases and early washout being more likely than NBNC-HCC. However, more imaging features need to be evaluated in a larger sample.
Predictive value of controlling nutritional status score in postoperative recurrence and metastasis of breast cancer patients with HER2-low expression
Authors: Li Yue , Zhang Yue , Zhou Zhaoyue , Shang Lingmin , Huang Yuanxi , Lu Xiangshi , Cheng Shaoqiang
Published: July 2023

Background

To investigate the predictive value of controlling nutritional status (CONUT) score in Postoperative Recurrence and Metastasis of Breast Cancer Patients with HER2-Low Expression.

Methods

The clinicopathological data of 697 female breast cancer patients who pathology confirmed invasive ductal carcinoma and surgery in Harbin Medical University Tumor Hospital from January 2014 to January 2017 were retrospectively analyzed. The relationship between CONUT score and various clinicopathological factors as well as prognosis was evaluated.

Results

Based on the cut-off point of ROC curve, compared with the low CONUT score group, the high CONUT score group had worse 5-year RFS. In subgroup analysis, compared with the low CONUT group, the high CONUT group had worse prognosis at different TNM stages. Univariate and multivariate results showed that the low CONUT score group had better overall survival and recurrence-free survival than the high CONUT group.

Conclusion

CONUT score is an independent predictor of postoperative recurrence and metastasis in HER2-low breast cancer patients. It is may be used as an effective tool to predict the recurrence and metastasis of HER2-low breast cancer.
Pembrolizumab plus lenvatinib in advanced endometrial cancer: case report and systematic review of lung toxicity
Authors: Staropoli Nicoletta , Salvino Angela , Falcone Federica , Farenza Valentina , Costa Martina , Rossini Giacomo , Manti Francesco , Crispino Antonella , Riillo Caterina , Ciliberto Domenico , Arbitrio Mariamena , Tassone Pierfrancesco , Tagliaferri Pierosandro
Published: July 2023

Background

The optimal strategy for the treatment of recurrent and/or advanced endometrial cancer is still undefined. Recently, despite the lack of any predictive biomarker, the combination of pembrolizumab with lenvatinib has improved survival outcomes. We here report the long-term management of lung toxicity in a patient with endometrial cancer, and we critically review the current therapeutic options for this disease.

Results

A patient with heavily pretreated endometrial cancer took pembrolizumab plus lenvatinib for 1 year, achieving a persistent partial response with a time to treatment failure of 18 months, despite relevant lung toxicity that did not affect the remarkable overall clinical benefit. A systematic review of this combination underlines the efficacy outcome despite toxicity. Interestingly, the literature review on lung toxicity suggested the role of anti-angiogenetic agents in the pathogenesis of lung cavitation, probably related to direct treatment activity, and disclosed a potential radiological sign predictive of the activity of anti-angiogenetic agents.

Conclusion

We underline the efficacy of pembrolizumab plus lenvatinib in the current treatment landscape of endometrial cancer, underscoring the relevance of a correct management of toxicity.
Hypoxia: syndicating triple negative breast cancer against various therapeutic regimens
Authors: Srivastava Nityanand , Usmani Salman Sadullah , Subbarayan Rajasekaran , Saini Rashmi , Pandey Pranav Kumar
Published: July 2023

Triple-negative breast cancer (TNBC) is one of the deadliest subtypes of breast cancer (BC) for its high aggressiveness, heterogeneity, and hypoxic nature. Based on biological and clinical observations the TNBC related mortality is very high worldwide. Emerging studies have clearly demonstrated that hypoxia regulates the critical metabolic, developmental, and survival pathways in TNBC, which include glycolysis and angiogenesis. Alterations to these pathways accelerate the cancer stem cells (CSCs) enrichment and immune escape, which further lead to tumor invasion, migration, and metastasis. Beside this, hypoxia also manipulates the epigenetic plasticity and DNA damage response (DDR) to syndicate TNBC survival and its progression. Hypoxia fundamentally creates the low oxygen condition responsible for the alteration in Hypoxia-Inducible Factor-1alpha (HIF-1α) signaling within the tumor microenvironment, allowing tumors to survive and making them resistant to various therapies. Therefore, there is an urgent need for society to establish target-based therapies that overcome the resistance and limitations of the current treatment plan for TNBC. In this review article, we have thoroughly discussed the plausible significance of HIF-1α as a target in various therapeutic regimens such as chemotherapy, radiotherapy, immunotherapy, anti-angiogenic therapy, adjuvant therapy photodynamic therapy, adoptive cell therapy, combination therapies, antibody drug conjugates and cancer vaccines. Further, we also reviewed here the intrinsic mechanism and existing issues in targeting HIF-1α while improvising the current therapeutic strategies. This review highlights and discusses the future perspectives and the major alternatives to overcome TNBC resistance by targeting hypoxia-induced signaling.
Diagnostic experience of intravenous leiomyomatosis with emphasis on conventional ultrasonography imaging: a single-center study
Authors: Ge Zhitong , Wang Yahong , Wang Ying , Li Wanying , Yang Xiao , Li Jianchu , Wang Hongyan
Published: July 2023

Objective

Intravenous leiomyomatosis (IVL) is a rare and aggressive tumor type that has the potential to extend into the inferior vena cava (IVC) and is susceptible to be misdiagnosed and neglected. Despite its clinical significance, there is a paucity of research that has focused on the specific manifestations of IVL on ultrasonography. Therefore, this study aims to systematically analyze the specific ultrasound features of IVL and augment its diagnostic accuracy.

Materials and method

Prospective inclusion was granted to patients admitted to our hospital between December 2016 and March 2021 for an IVC-occupying lesion. Multi-modal ultrasonography, encompassing gray-scale and color Doppler, was conducted. Lesions were categorized as IVL or non-IVL based on pathological or follow-up data. Two ultrasound sonographers with over 5 years of experience read and recorded ultrasound data for all lesions, which were subsequently comparatively analyzed to identify specific signs of IVL.

Results

A total of 284 patients diagnosed with IVC-occupying lesions were included in the study. The lesion types comprised of IVL (n=67, 23.6%), IVC thrombus (n=135, 47.5%), tumor thrombus of renal carcinoma involving the IVC (n=35, 12.4%), tumor thrombus of liver carcinoma involving the IVC (n=24, 8.5%), leiomyosarcoma of the IVC (n=14, 4.9%), and tumor thrombus of adrenocortical adenocarcinoma (n=9, 4.1%). The presence of “sieve hole” and “multi-track” signs was observed in 20 IVL lesions under the grey-scale modality, while both signs were absent in the non-IVL group (P<0.01). The study found no statistically significant differences in the presentation of “sieve hole” and “multi-track” signs under the grey-scale and color Doppler modalities in cases of intravascular lithotripsy (IVL) (P>0.05). Using these two signs as diagnostic criteria for IVL, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), miss rate, misdiagnosis rate, and accuracy were determined to be 29.9%, 100%, 100%, 82.2%, 70.1%, 0, and 83.5%, respectively (AUC ROC=0.649; 95%CI: 0.537-0.761).

Conclusion

IVL exhibits distinct ultrasound presentations, including “sieve hole” and “multi-track” signs, which demonstrate high specificity and accuracy as diagnostic indicators. Furthermore, these signs are corroborated by pathological evidence and effectively distinguish IVL from other lesions occupying the IVC.
Theoretical design for covering Engeletin with functionalized nanostructure-lipid carriers as neuroprotective agents against Huntington’s disease via the nasal-brain route
Authors: Smriti  , Singla Madhav , Gupta Saurabh , Porwal Omji , Nasser Binjawhar Dalal , Sayed Amany A. , Mittal Pooja , El-Demerdash Fatma M. , Algahtani Mohammad , Singh Sachin Kumar , Dua Kamal , Gupta Gaurav , Bawa Puneet , Altyar Ahmed E. , Abdel-Daim Mohamed M.
Published: July 2023

Objective:To propose a theoretical formulation of engeletin-nanostructured lipid nanocarriers for improved delivery and increased bioavailability in treating Huntington’s disease (HD).

Methods:We conducted a literature review of the pathophysiology of HD and the limitations of currently available medications. We also reviewed the potential therapeutic benefits of engeletin, a flavanol glycoside, in treating HD through the Keap1/nrf2 pathway. We then proposed a theoretical formulation of engeletin-nanostructured lipid nanocarriers for improved delivery across the blood-brain barrier (BBB) and increased bioavailability.

Results:HD is an autosomal dominant neurological illness caused by a repetition of the cytosine-adenine-guanine trinucleotide, producing a mutant protein called Huntingtin, which degenerates the brain’s motor and cognitive functions. Excitotoxicity, mitochondrial dysfunction, oxidative stress, elevated concentration of ROS and RNS, neuroinflammation, and protein aggregation significantly impact HD development. Current therapeutic medications can postpone HD symptoms but have long-term adverse effects when used regularly. Herbal medications such as engeletin have drawn attention due to their minimal side effects. Engeletin has been shown to reduce mitochondrial dysfunction and suppress inflammation through the Keap1/NRF2 pathway. However, its limited solubility and permeability hinder it from reaching the target site. A theoretical formulation of engeletin-nanostructured lipid nanocarriers may allow for free transit over the BBB due to offering a similar composition to the natural lipids present in the body a lipid solubility and increase bioavailability, potentially leading to a cure or prevention of HD.

Conclusion:The theoretical formulation of engeletin-nanostructured lipid nanocarriers has the potential to improve delivery and increase the bioavailability of engeletin in the treatment of HD, which may lead to a cure or prevention of this fatal illness.
Prediction of guidewire-induced aortic deformations during EVAR: a finite element and in vitro study
Authors: Emendi Monica , Støverud Karen H. , Tangen Geir A. , Ulsaker Håvard , Manstad-H Frode , Di Giovanni Pierluigi , Dahl Sigrid K. , Langø Thomas , Prot Victorien
Published: July 2023

Introduction and aims: During an Endovascular Aneurysm Repair (EVAR) procedure a stiff guidewire is inserted from the iliac arteries. This induces significant deformations on the vasculature, thus, affecting the pre-operative planning, and the accuracy of image fusion. The aim of the present work is to predict the guidewire induced deformations using a finite element approach validated through experiments with patient-specific additive manufactured models. The numerical approach herein developed could improve the pre-operative planning and the intra-operative navigation.

Material and methods: The physical models used for the experiments in the hybrid operating room, were manufactured from the segmentations of pre-operative Computed Tomography (CT) angiographies. The finite element analyses (FEA) were performed with LS-DYNA Explicit. The material properties used in finite element analyses were obtained by uniaxial tensile tests. The experimental deformed configurations of the aorta were compared to those obtained from FEA. Three models, obtained from Computed Tomography acquisitions, were investigated in the present work: A) without intraluminal thrombus (ILT), B) with ILT, C) with ILT and calcifications.

Results and discussion: A good agreement was found between the experimental and the computational studies. The average error between the final in vitro vs. in silico aortic configurations, i.e., when the guidewire is fully inserted, are equal to 1.17, 1.22 and 1.40 mm, respectively, for Models A, B and C. The increasing trend in values of deformations from Model A to Model C was noticed both experimentally and numerically. The presented validated computational approach in combination with a tracking technology of the endovascular devices may be used to obtain the intra-operative configuration of the vessels and devices prior to the procedure, thus limiting the radiation exposure and the contrast agent dose.
Towards further understanding the applications of endophytes: enriched source of bioactive compounds and bio factories for nanoparticles
Authors: Choudhary Nisha , Dhingra Naveen , Gacem Amel , Yadav Virendra Kumar , Verma Rakesh Kumar , Choudhary Mahima , Bhardwaj Uma , Chundawat Rajendra Singh , Alqahtani Mohammed S. , Gaur Rajarshi Kumar , Eltayeb Lienda Bashier , Al Abdulmonem Waleed , Jeon Byong-Hun
Published: July 2023

The most significant issues that humans face today include a growing population, an altering climate, an growing reliance on pesticides, the appearance of novel infectious agents, and an accumulation of industrial waste. The production of agricultural goods has also been subject to a great number of significant shifts, often known as agricultural revolutions, which have been influenced by the progression of civilization, technology, and general human advancement. Sustainable measures that can be applied in agriculture, the environment, medicine, and industry are needed to lessen the harmful effects of the aforementioned problems. Endophytes, which might be bacterial or fungal, could be a successful solution. They protect plants and promote growth by producing phytohormones and by providing biotic and abiotic stress tolerance. Endophytes produce the diverse type of bioactive compounds such as alkaloids, saponins, flavonoids, tannins, terpenoids, quinones, chinones, phenolic acids etc. and are known for various therapeutic advantages such as anticancer, antitumor, antidiabetic, antifungal, antiviral, antimicrobial, antimalarial, antioxidant activity. Proteases, pectinases, amylases, cellulases, xylanases, laccases, lipases, and other types of enzymes that are vital for many different industries can also be produced by endophytes. Due to the presence of all these bioactive compounds in endophytes, they have preferred sources for the green synthesis of nanoparticles. This review aims to comprehend the contributions and uses of endophytes in agriculture, medicinal, industrial sectors and bio-nanotechnology with their mechanism of action.
How robust are egocentric and altercentric interference effects in social cognition? a test with explicit and implicit versions of a continuous false belief task
Authors: Haskaraca Feride Nur , Proft Marina , Liszkowski Ulf , Rakoczy Hannes
Published: July 2023

It has been long assumed that meta-representational theory of mind (ToM) -our ability to ascribe mental states to ourselves and other people- emerges around age four as indicated in performance on explicit verbal false belief tasks. In contrast, newer studies assessing false belief understanding with implicit, non-verbal measures suggest that some form of ToM may be present even in infancy. But these studies now face replication issues, and it remains unclear whether they can provide robust evidence for implicit ToM. One line of research on implicit ToM, however, may remain promising: Studies that tap so-called altercentric biases. Such biases occur when agents in their judgments about the world are influenced (perform slower, more error-prone) in light of another agent’s deviating perspective even if that perspective is completely irrelevant to the task; they thus can be seen as indicators of spontaneous and implicit ToM. Altercentric biases are the mirror images of egocentric biases (agents are influenced by their own perspective when evaluating another agent’s deviating perspective). In three studies with adults, we aimed to tap both egocentric and altercentric interference effects within the same task format. We used the so-called Sandbox task, a false belief task with continuous locations. In Study 1, we tested an online adaptation of the Sandbox task, which we also used to explore potential cross-cultural differences in these biases. Studies 2 and 3 combined the Sandbox task with mouse-tracking measures. These studies revealed neither egocentric nor altercentric biases. These null results are discussed with regard to the question whether absence of evidence here may present evidence of absence of such spontaneous perspective-taking biases or merely false negatives.
New approach methodologies to facilitate and improve the hazard assessment of non-genotoxic carcinogens—a PARC project
Authors: Audebert Marc , Assmann Ann-Sophie , Azqueta Amaya , Babica Pavel , Benfenati Emilio , Bortoli Sylvie , Bouwman Peter , Braeuning Albert , Burgdorf Tanja , Coumoul Xavier , Debizet Kloé , Dusinska Maria , Ertych Norman , Fahrer Jörg , Fetz Verena , Le Hégarat Ludovic , López de Cerain Adela , Heusinkveld Harm J. , Hogeveen Kevin , Jacobs Miriam N. , Luijten Mirjam , Raitano Giuseppa , Recoules Cynthia , Rundén-Pran Elise , Saleh Mariam , Sovadinová Iva , Stampar Martina , Thibol Lea , Tomkiewicz Céline , Vettorazzi Ariane , Van de Water Bob , El Yamani Naouale , Zegura Bojana , Oelgeschläger Michael
Published: July 2023

Carcinogenic chemicals, or their metabolites, can be classified as genotoxic or non-genotoxic carcinogens (NGTxCs). Genotoxic compounds induce DNA damage, which can be detected by an established in vitro and in vivo battery of genotoxicity assays. For NGTxCs, DNA is not the primary target, and the possible modes of action (MoA) of NGTxCs are much more diverse than those of genotoxic compounds, and there is no specific in vitro assay for detecting NGTxCs. Therefore, the evaluation of the carcinogenic potential is still dependent on long-term studies in rodents. This 2-year bioassay, mainly applied for testing agrochemicals and pharmaceuticals, is time-consuming, costly and requires very high numbers of animals. More importantly, its relevance for human risk assessment is questionable due to the limited predictivity for human cancer risk, especially with regard to NGTxCs. Thus, there is an urgent need for a transition to new approach methodologies (NAMs), integrating human-relevant in vitro assays and in silico tools that better exploit the current knowledge of the multiple processes involved in carcinogenesis into a modern safety assessment toolbox. Here, we describe an integrative project that aims to use a variety of novel approaches to detect the carcinogenic potential of NGTxCs based on different mechanisms and pathways involved in carcinogenesis. The aim of this project is to contribute suitable assays for the safety assessment toolbox for an efficient and improved, internationally recognized hazard assessment of NGTxCs, and ultimately to contribute to reliable mechanism-based next-generation risk assessment for chemical carcinogens.
Research on the Vibration Reduction Mechanism of a New Tensioning Platform with an Embedded Superstructure
Authors: Sun Xiaoqing , Yang Zhengyin , Wang Ju , Hou Xiusong , Yang Yikun
Published: July 2023

Aiming at the problem of precision driving and vibration suppression for sensitive payloads on-orbit, this paper proposes a new compliant platform based on an embedded superstructure and a smart material actuator. Firstly, the main structure of the platform is designed and optimized to achieve the expected indicators via the response surface method. Then, the vibration reduction mechanism of the platform with the embedded superstructure is studied by establishing an equivalent model. Following that, a four-phase superstructure is matched and designed with a compact space, and the results are verified by finite element modal analysis. Finally, both the tensioning performance and vibration reduction performance under fixed frequency harmonic disturbance are studied via transient dynamic simulation. Based on the obtained results, directions for future improvements are proposed. The relevant conclusions can provide a reference for function integration of precision tensioning and vibration suppression.
Fundamental Study of Premixed Methane Air Combustion in Extreme Turbulent Conditions Using PIV and C-X CH PLIF
Authors: Hossain Md. Amzad , Islam Md Nawshad Arslan , De La Torre Martin , Zamora Arturo Acosta , Choudhuri Ahsan
Published: July 2023

This paper presents the flow and flame characteristics of a highly turbulent reactive flow over a backward-facing step inside a windowed combustor. Flow and combustion experiments were performed at Re = 15,000 and Re = 30,000 using high-resolution 10 kHz PIV and 10 kHz PLIF diagnostic techniques. Grid turbulators (Grid) with two different hole diameters (HD of 1.5 mm and 3 mm) and blockage ratios (BR of 46%, 48%, 62%, and 63%) were considered for the turbulence study. Grids introduced different turbulent length scales (LT) in the flow, causing the small eddies and turbulence intensity to increase downstream. The backward-facing step increased the turbulence level in the recirculation zone. This helped to anchor the flame in that zone. The small HD grids (Grids 1 and 3) produced continuous fluid structures (small-scale), whereas the larger HD grids (Grids 2 and 4) produced large-scale fluid structures. Consequently, the velocity fluctuation was lower (~25.6 m/s) under small HD grids and higher (~27.7 m/s) under large HD grids. The flame study was performed at Φ = 0.8, 1.0, and 1.2 using C-X CH PLIF. An Adaptive MATLAB-based flame imaging scheme has been developed for turbulent reacting flows. Grids 1 and 3 induced more wrinkles in the flame due to higher thermal instabilities, pressure fluctuation, and diffusion under those grids. The flamelet breakdown and burnout events were higher under Grids 2 and 4 due to higher thermal diffusivity and a slower diffusion rate. It was observed that the flame wrinkling and flame stretching are higher at Re = 30,000 compared to Re = 15,000. The Borghi–Peters diagram showed that the flames were within the thin reaction zone except for Grid 1 at Re = 15,000, where flames fell in the corrugated zone. It was observed from PIV and PLIF analyses that Re and LT mostly controlled the flame and flow characteristics.
Fuzzy Neural Network PID Control Used in Individual Blade Control
Authors: Yang Renguo , Gao Yadong , Wang Huaming , Ni Xianping
Published: July 2023

In order to further reduce the vibration level of helicopters, the active vibration control technology of helicopters has been extensively studied. Among them, individual blade control (IBC) independently applies high-order harmonics to each blade with an actuator, which can improve the aerodynamic environment of the blade and effectively reduce the vibration load of the hub. The rotor structural dynamics model based on the Hamilton energy variation principle and the medium deformation beam theory were established firstly, and the aerodynamic model based on the dynamic inflow model and the Leishman–Beddoes unsteady aerodynamic model were also established. The structural finite element method and the direct numerical integration method were used to calculate the vibration response of the rotor to determine the vibration load of the hub. After these, the steepest descent-golden section combinatorial optimization algorithm was used to find the optimization parameters of IBC. Based on this, the input parameters of fuzzy neural network PID control were determined, and the rotor hub vibration load control simulation was conducted. Under the effect of IBC, the vibration loads of the hub could be reduced by about 60%. The article gives the best control laws of individual harmonic pitch control and their combinations. These results can theoretically be applied to the design of control law to reduce helicopter vibration loads.
Disease Detection and Identification of Rice Leaf Based on Improved Detection Transformer
Authors: Yang Hua , Deng Xingquan , Shen Hao , Lei Qingfeng , Zhang Shuxiang , Liu Neng
Published: July 2023

In recent years, the domain of diagnosing plant afflictions has predominantly relied upon the utilization of deep learning techniques for classifying images of diseased specimens; however, these classification algorithms remain insufficient for instances where a single plant exhibits multiple ailments. Consequently, we view the region afflicted by the malady of rice leaves as a minuscule issue of target detection, and then avail ourselves of a computational approach to vision to identify the affected area. In this paper, we advance a proposal for a Dense Higher-Level Composition Feature Pyramid Network (DHLC-FPN) that is integrated into the Detection Transformer (DETR) algorithm, thereby proffering a novel Dense Higher-Level Composition Detection Transformer (DHLC-DETR) methodology which can effectively detect three diseases: sheath blight, rice blast, and flax spot. Initially, the proposed DHLC-FPN is utilized to supersede the backbone network of DETR through amalgamation with Res2Net, thus forming a feature extraction network. Res2Net then extracts five feature scales, which are coalesced through the deployment of high-density rank hybrid sampling by the DHLC-FPN architecture. The fused features, in concert with the location encoding, are then fed into the transformer to produce predictions of classes and prediction boxes. Lastly, the prediction classes and the prediction boxes are subjected to binary matching through the application of the Hungarian algorithm. On the IDADP datasets, the DHLC-DETR model, through the utilization of data enhancement, elevated mean Average Precision (mAP) by 17.3% in comparison to the DETR model. Additionally, mAP for small target detection was improved by 9.5%, and the magnitude of hyperparameters was reduced by 324.9 M. The empirical outcomes demonstrate that the optimized structure for feature extraction can significantly enhance the average detection accuracy and small target detection accuracy of the model, achieving an average accuracy of 97.44% on the IDADP rice disease dataset.
Technology of Automatic Evaluation of Dairy Herd Fatness
Authors: Yurochka Sergey S. , Dovlatov Igor M. , Pavkin Dmitriy Y. , Panchenko Vladimir A. , Smirnov Aleksandr A. , Proshkin Yuri A. , Yudaev Igor
Published: July 2023

The global recent development trend in dairy farming emphasizes the automation and robotization of milk production. The rapid development rate of dairy farming requires new technologies to increase the economic efficiency and improve production. The research goal was to increase the milk production efficiency by introducing the technology to automatically assess the fatness of a dairy herd in 0.25-point step on a 5-point scale. Experimental data were collected on the 3D ToF camera O3D 303 installed in a walk-through machine on robotic free-stall farms in the period from August 2020 to November 2022. The authors collected data on 182 animals and processed 546 images. All animals were between 450 and 700 kg in weight. Based on the regression analysis, they developed software to find and identify the main five regions of interest: the spinous processes of the lumbar spine and back; the transverse processes of the lumbar spine and the gluteal fossa area; the malar and sciatic tuberosities; the tail base; and the vulva and anus region. The adequacy of the proposed technology was verified by means of a parallel expert survey. The developed technology was tested on 3 farms with a total of 1810 cows and is helpful for the non-contact evaluation of the fatness of a dairy herd within the herd’s life cycle. The developed method can be used to evaluate the tail base area with 100% accuracy. The hungry hole can be determined with a 98.9% probability; the vulva and anus area—with a 95.10% probability. Protruding vertebrae—namely, spinous processes and transverse processes—were evaluated with a 52.20% and 51.10% probability. The system’s overall accuracy was assessed as 93.4%, which was a positive result. Animals in the condition of 2.5 to 3.5 at 5–6 months were considered healthy. The developed system makes it possible to divide the animals into three groups, confirming their physiological status: normal range body condition, exhaustion, and obesity. By means of a correlation dependence equal to R = 0.849 (Pearson method), the authors revealed that animals of the same breed and in the same lactation range have a linear dependence of weight-to-fatness score. They have developed an algorithm for automated assessment of the fatness of animals with further staging of their physiological state. The economic effect of implementing the proposed system has been demonstrated. The effect of increasing the production efficiency of a dairy farm by introducing the technology of automatic evaluation of the fatness of a dairy herd with a 0.25-point step on a 5-point scale had been achieved. The overall accuracy of the system was estimated at 93.4%.