bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Embedded Nanoparticles on the Phonon Spectrum of Ice: An Inelastic X-ray Scattering Study
Authors: De Francesco Alessio , Scaccia Luisa , Formisano Ferdinando , Guarini Eleonora , Bafile Ubaldo , Nykypanchuk Dmytro , Alatas Ahmet , Li Mingda , Lynch Scott T. , Cunsolo Alessandro
Published: March 2023

As a contribution to the ongoing effort toward high-frequency sound manipulation in composite materials, we use Inelastic X-ray Scattering to probe the phonon spectrum of ice, either in a pure form or with a sparse amount of nanoparticles embedded in it. The study aims at elucidating the ability of nanocolloids to condition the collective atomic vibrations of the surrounding environment. We observe that a nanoparticle concentration of about 1 % in volume is sufficient to visibly affect the phonon spectrum of the icy substrate, mainly canceling its optical modes and adding nanoparticle phonon excitations to it. We highlight this phenomenon thanks to the lineshape modeling based on a Bayesian inference, which enables us to capture the finest detail of the scattering signal. The results of this study can empower new routes toward the shaping of sound propagation in materials through the control of their structural heterogeneity.
Nanomaterial Characterization in Complex Media—Guidance and Application
Authors: Hachenberger Yves Uwe , Rosenkranz Daniel , Kromer Charlotte , Krause Benjamin Christoph , Dreiack Nadine , Kriegel Fabian Lukas , Koz’menko Ekaterina , Jungnickel Harald , Tentschert Jutta , Bierkandt Frank Stefan , Laux Peter , Panne Ulrich , Luch Andreas
Published: March 2023

A broad range of inorganic nanoparticles (NPs) and their dissolved ions possess a possible toxicological risk for human health and the environment. Reliable and robust measurements of dissolution effects may be influenced by the sample matrix, which challenges the analytical method of choice. In this study, CuO NPs were investigated in several dissolution experiments. Two analytical techniques (dynamic light scattering (DLS) and inductively-coupled plasma mass spectrometry (ICP-MS)) were used to characterize NPs (size distribution curves) time-dependently in different complex matrices (e.g., artificial lung lining fluids and cell culture media). The advantages and challenges of each analytical approach are evaluated and discussed. Additionally, a direct-injection single particle (DI sp)ICP-MS technique for assessing the size distribution curve of the dissolved particles was developed and evaluated. The DI technique provides a sensitive response even at low concentrations without any dilution of the complex sample matrix. These experiments were further enhanced with an automated data evaluation procedure to objectively distinguish between ionic and NP events. With this approach, a fast and reproducible determination of inorganic NPs and ionic backgrounds can be achieved. This study can serve as guidance when choosing the optimal analytical method for NP characterization and for the determination of the origin of an adverse effect in NP toxicity.
cMIND Diet, Indoor Air Pollution, and Depression: A Cohort Study Based on the CLHLS from 2011 to 2018
Authors: Wang Ruoyu , Ye Chen , Huang Xiaojie , Halimulati Mairepaiti , Sun Meng , Ma Yuxin , Fan Rui , Zhang Zhaofeng
Published: March 2023

This study aims to explore the interaction between a Chinese version of the Mediterranean–DASH intervention for neurodegenerative delay (cMIND) diet and indoor air pollution and its effect on depression among older adults. This cohort study used 2011–2018 data from the Chinese Longitudinal Healthy Longevity Survey. Participants included 2724 adults aged 65 and older without depression. The Chinese version of the Mediterranean–DASH intervention for neurodegenerative delay (cMIND) diet scores ranged from 0 to 12 based on validated food frequency questionnaire responses. Depression was measured using the Phenotypes and eXposures Toolkit. Cox proportional hazards regression models were used to explore the associations, and the analysis was stratified using the cMIND diet scores. A total of 2724 participants (54.3% males and 45.9% 80 years and older) at baseline were included. Living with severe indoor pollution was associated with a 40% increase in the risk of depression (HR: 1.40, 95% CI: 1.07, 1.82) compared to living without indoor pollution. Indoor air pollution exposure was significantly associated with cMIND diet scores. Participants with a lower cMIND diet score (HR: 1.72, 95% CI: 1.24, 2.38) had a greater association with severe pollution than those with a higher cMIND diet score. The cMIND diet may alleviate depression caused by indoor pollution among older adults.
Sustainable Production of Ajuga Bioactive Metabolites Using Cell Culture Technologies: A Review
Authors: Popova Elena , Titova Maria , Tynykulov Marat , Zakirova Rano P. , Kulichenko Irina , Prudnikova Olga , Nosov Alexander
Published: March 2023

The genus Ajuga (Lamiaceae) is rich in medicinally important species with biological activities ranging from anti-inflammatory, antitumor, neuroprotective, and antidiabetic to antibacterial, antiviral, cytotoxic, and insecticidal effects. Every species contains a unique and complex mixture of bioactive metabolites—phytoecdysteroids (PEs), iridoid glycosides, withanolides, neo-clerodane terpenoids, flavonoids, phenolics, and other chemicals with high therapeutic potential. Phytoecdysteroids, the main compounds of interest, are natural anabolic and adaptogenic agents that are widely used as components of dietary supplements. Wild plants remain the main source of Ajuga bioactive metabolites, particularly PEs, which leads to frequent overexploitation of their natural resources. Cell culture biotechnologies offer a sustainable approach to the production of vegetative biomass and individual phytochemicals specific for Ajuga genus. Cell cultures developed from eight Ajuga taxa were capable of producing PEs, a variety of phenolics and flavonoids, anthocyanins, volatile compounds, phenyletanoid glycosides, iridoids, and fatty acids, and demonstrated antioxidant, antimicrobial, and anti-inflammatory activities. The most abundant PEs in the cell cultures was 20-hydroxyecdysone, followed by turkesterone and cyasterone. The PE content in the cell cultures was comparable or higher than in wild or greenhouse plants, in vitro-grown shoots, and root cultures. Elicitation with methyl jasmonate (50–125 µM) or mevalonate and induced mutagenesis were the most effective strategies that stimulated cell culture biosynthetic capacity. This review summarizes the current progress in cell culture application for the production of pharmacologically important Ajuga metabolites, discusses various approaches to improve the compound yield, and highlights the potential directions for future interventions.
The Impact of Sarcopenia Onset Prior to Cancer Diagnosis on Cancer Survival: A National Population-Based Cohort Study Using Propensity Score Matching
Authors: Su Chih-Hsiung , Chen Wan-Ming , Chen Ming-Chih , Shia Ben-Chang , Wu Szu-Yuan
Published: March 2023

Purpose: The relationship between the onset of sarcopenia prior to cancer diagnosis and survival outcomes in various types of cancer is not well understood. To address this gap in knowledge, we conducted a propensity score-matched population-based cohort study to compare the overall survival of cancer patients with and without sarcopenia. Patients and Methods: In our study, we included patients with cancer and divided them into two groups based on the presence or absence of sarcopenia. To ensure comparability between the groups, we matched patients in both groups at a ratio of 1:1. Results: After the matching process, our final cohort included 20,416 patients with cancer (10,208 in each group) who were eligible for further analysis. There were no significant differences between the sarcopenia and nonsarcopenia groups in terms of confounding factors such as age (mean 61.05 years versus 62.17 years), gender (52.56% versus 52.16% male, 47.44% versus 47.84% female), comorbidities, and cancer stages. In our multivariate Cox regression analysis, we found that the adjusted hazard ratio (aHR; 95% confidence interval [CI]) of all-cause death for the sarcopenia group compared to the nonsarcopenia group was 1.49 (1.43–1.55; p < 0.001). Additionally, the aHRs (95% CIs) of all-cause death for those aged 66–75, 76–85, and >85 years (compared to those aged ≤65 years) were 1.29 (1.23–1.36), 2.00 (1.89–2.12), and 3.26 (2.97–3.59), respectively. The aHR (95% CI) of all-cause death for those with a Charlson comorbidity index (CCI) ≥ 1 compared to those with a CCI of 0 was 1.34 (1.28–1.40). The aHR (95% CI) of all-cause death for men compared to women was 1.56 (1.50–1.62). When comparing the sarcopenia and nonsarcopenia groups, the aHRs (95% CIs) for lung, liver, colorectal, breast, prostate, oral, pancreatic, stomach, ovarian, and other cancers were significantly higher. Conclusion: Our findings suggest that the onset of sarcopenia prior to cancer diagnosis may be linked to reduced survival outcomes in cancer patients.
Exploring the Longitudinal Stability of Food Neophilia and Dietary Quality and Their Prospective Relationship in Older Adults: A Cross-Lagged Panel Analysis
Authors: Wortmann Hanna R. , Gisch Ulrike A. , Bergmann Manuela M. , Warschburger Petra
Published: March 2023

Poor dietary quality is a major cause of morbidity, making the promotion of healthy eating a societal priority. Older adults are a critical target group for promoting healthy eating to enable healthy aging. One factor suggested to promote healthy eating is the willingness to try unfamiliar foods, referred to as food neophilia. This two-wave longitudinal study explored the stability of food neophilia and dietary quality and their prospective relationship over three years, analyzing self-reported data from N = 960 older adults (MT1 = 63.4, range = 50–84) participating in the NutriAct Family Study (NFS) in a cross-lagged panel design. Dietary quality was rated using the NutriAct diet score, based on the current evidence for chronic disease prevention. Food neophilia was measured using the Variety Seeking Tendency Scale. The analyses revealed high a longitudinal stability of both constructs and a small positive cross-sectional correlation between them. Food neophilia had no prospective effect on dietary quality, whereas a very small positive prospective effect of dietary quality on food neophilia was found. Our findings give initial insights into the positive relation of food neophilia and a health-promoting diet in aging and underscore the need for more in-depth research, e.g., on the constructs’ developmental trajectories and potential critical windows of opportunity for promoting food neophilia.
High Protein Intake at Lunch Is Negatively Associated with Blood Pressure in Community-Dwelling Older Adults: A Cross-Sectional Study
Authors: Coelho-Júnior Hélio José , Aguiar Samuel da Silva , Gonçalves Ivan de Oliveira , Calvani Riccardo , Tosato Matteo , Landi Francesco , Picca Anna , Marzetti Emanuele
Published: March 2023

Background: The present study was conducted to explore the association between protein intake across the main meals and hypertension (HTN)-related parameters in community-dwelling Brazilian older adults. Methods: Brazilian community-dwelling older adults were recruited in a senior center. Dietary habits were assessed through 24 h recall. Protein intake was classified as high and low according to median and recommended dietary allowance values. Absolute and body weight (BW)–adjusted protein consumption levels were quantified and analyzed according to ingestion across the main meals. Systolic (SBP) and diastolic blood pressure (DBP) were measured using an oscilometric monitor. Participants were categorized as hypertensive according to physician diagnosis or the detection of high SBP and/or DBP values. Results: One hundred ninety-seven older adults were enrolled in the present study. Protein intake at lunch was independently and negatively associated with SBP. Furthermore, a lower prevalence of HTN (diagnosed by a physician) was observed in participants with higher intakes of protein. These results remained significant after adjustment for many covariates. However, significance was lost when kilocalories and micronutrients were included in the model. Conclusions: Findings of the present study indicate that protein intake at lunch was independently and negatively associated with systolic BP in community-dwelling older adults.
Effect of Walnut Supplementation on Dietary Polyphenol Intake and Urinary Polyphenol Excretion in the Walnuts and Healthy Aging Study
Authors: Amen Rita I. , Sirirat Rawiwan , Oda Keiji , Rajaram Sujatha , Nwachukwu Ifeanyi , Cofan Montserrat , Ros Emilio , Sabate Joan , Haddad Ella H.
Published: March 2023

Among all tree nuts, walnuts contain the highest total polyphenols by weight. This secondary data analysis examined the effect of daily walnut supplementation on the total dietary polyphenols and subclasses and the urinary excretion of total polyphenols in a free-living elderly population. In this 2-year prospective, randomized intervention trial (ID NCT01634841), the dietary polyphenol intake of participants who added walnuts daily to their diets at 15% of daily energy were compared to those in the control group that consumed a walnut-free diet. Dietary polyphenols and subclasses were estimated from 24 h dietary recalls. Phenolic estimates were derived from Phenol-Explorer database version 3.6. Participants in the walnut group compared to the control group had a higher intake of total polyphenols, flavonoids, flavanols, and phenolic acids in mg/d (IQR): 2480 (1955, 3145) vs. 1897 (1369, 2496); 56 (42,84) vs. 29 (15, 54); 174 (90, 298) vs. 140 (61, 277); and 368 (246, 569) vs. 242 (89, 398), respectively. There was a significant inverse association between dietary flavonoid intake and urine polyphenol excretion; less urinary excretion may imply that some of the polyphenols were eliminated via the gut. Nuts had a significant contribution to the total polyphenols in the diet, suggesting that a single food like walnuts added to habitual diet can increase the polyphenol intake in a Western population.
Chronic Nonbacterial Osteomyelitis of the Jaw in a 3-Year-Old Girl
Authors: Makino Shigeru , Oshige Hideo , Shinozuka Jun , Imashuku Shinsaku
Published: March 2023

Differential diagnosis of bacterial osteomyelitis (BOM) and chronic nonbacterial osteomyelitis (CNO) is challenging. Pediatric CNO can be diagnosed at around 10 years of age and when CNO cases involve only the jaw, it is difficult to make a diagnosis in a young child. A 3-year-old female developed CNO at the jaw alone. She presented with no fever, right jaw pain, mild trismus, and a preauricular facial swelling around the right mandible. Computed tomography (CT) revealed a hyperostotic right mandible, with osteolytic and sclerotic changes associated with periosteal reaction. At first, we suspected BOM and antibiotics were administered. Subsequently, CNO was diagnosed, and the patient received flurbiprofen (a nonsteroidal anti-inflammatory drug (NSAIDs)). Lack of a sufficient response led to successful treatment with a combination of oral alendronate and flurbiprofen. Physicians should be aware of CNO, a rare autoinflammatory noninfectious bone disease of unknown etiology, even in young children, although the disease mostly affects older children and adolescents.
Mechanisms of Neurorespiratory Toxicity Induced by Fentanyl Analogs—Lessons from Animal Studies
Authors: Chamoun Karam , Chevillard Lucie , Hajj Aline , Callebert Jacques , Mégarbane Bruno
Published: March 2023

In 2020, fentanyl and its analogs contributed to ~65% of drug-attributed fatalities in the USA, with a threatening increasing trend during the last ten years. These synthetic opioids used as potent analgesics in human and veterinary medicine have been diverted to recreational aims, illegally produced and sold. Like all opioids, central nervous system depression resulting from overdose or misuse of fentanyl analogs is characterized clinically by the onset of consciousness impairment, pinpoint miosis and bradypnea. However, contrasting with what observed with most opioids, thoracic rigidity may occur rapidly with fentanyl analogs, contributing to increasing the risk of death in the absence of immediate life support. Various mechanisms have been proposed to explain this particularity associated with fentanyl analogs, including the activation of noradrenergic and glutamatergic coerulospinal neurons and dopaminergic basal ganglia neurons. Due to the high affinities to the mu-opioid receptor, the need for more elevated naloxone doses than usually required in morphine overdose to reverse the neurorespiratory depression induced by fentanyl analogs has been questioned. This review on the neurorespiratory toxicity of fentanyl and analogs highlights the need for specific research focused on these agents to better understand the involved mechanisms of toxicity and develop dedicated strategies to limit the resulting fatalities.
Curcumin and Andrographis Exhibit Anti-Tumor Effects in Colorectal Cancer via Activation of Ferroptosis and Dual Suppression of Glutathione Peroxidase-4 and Ferroptosis Suppressor Protein-1
Authors: Miyazaki Katsuki , Xu Caiming , Shimada Mitsuo , Goel Ajay
Published: March 2023

Colorectal cancer (CRC) is the leading cause of cancer-related deaths worldwide. The limitations of current chemotherapeutic drugs in CRC include their toxicity, side effects, and exorbitant costs. To assess these unmet needs in CRC treatment, several naturally occurring compounds, including curcumin and andrographis, have gained increasing attention due to their multi-targeted functionality and safety vs. conventional drugs. In the current study, we revealed that a combination of curcumin and andrographis exhibited superior anti-tumor effects by inhibiting cell proliferation, invasion, colony formation, and inducing apoptosis. Genome-wide transcriptomic expression profiling analysis revealed that curcumin and andrographis activated the ferroptosis pathway. Moreover, we confirmed the gene and protein expression of glutathione peroxidase 4 (GPX-4) and ferroptosis suppressor protein 1 (FSP-1), the two major negative regulators of ferroptosis, were downregulated by this combined treatment. With this regimen, we also observed that intracellular accumulation of reactive oxygen species and lipid peroxides were induced in CRC cells. These cell line findings were validated in patient-derived organoids. In conclusion, our study revealed that combined treatment with curcumin and andrographis exhibited anti-tumorigenic effects in CRC cells through activation of ferroptosis and by dual suppression of GPX-4 and FSP-1, which have significant potential implications for the adjunctive treatment of CRC patients.
The Role of Tocotrienol in Arthritis Management—A Scoping Review of Literature
Authors: Tejpal Singh Hashwin Singh , Aminuddin Alya Aqilah , Pang Kok-Lun , Ekeuku Sophia Ogechi , Chin Kok-Yong
Published: March 2023

Arthritis is a cluster of diseases impacting joint health and causing immobility and morbidity in the elderly. Among the various forms of arthritis, osteoarthritis (OA) and rheumatoid arthritis (RA) are the most common. Currently, satisfying disease-modifying agents for arthritis are not available. Given the pro-inflammatory and oxidative stress components in the pathogenesis of arthritis, tocotrienol, a family of vitamin E with both anti-inflammatory and antioxidant properties, could be joint-protective agents. This scoping review aims to provide an overview of the effects of tocotrienol on arthritis derived from the existing scientific literature. A literature search using PubMed, Scopus and Web of Science databases was conducted to identify relevant studies. Only cell culture, animal and clinical studies with primary data that align with the objective of this review were considered. The literature search uncovered eight studies investigating the effects of tocotrienol on OA (n = 4) and RA (n = 4). Most of the studies were preclinical and revealed the positive effects of tocotrienol in preserving joint structure (cartilage and bone) in models of arthritis. In particular, tocotrienol activates the self-repair mechanism of chondrocytes exposed to assaults and attenuates osteoclastogenesis associated with RA. Tocotrienol also demonstrated strong anti-inflammatory effects in RA models. The single clinical trial available in the literature showcases that palm tocotrienol could improve joint function among patients with OA. In conclusion, tocotrienol could be a potential anti-arthritic agent pending more results from clinical studies.
Polylactic Acid/Poly(vinylpyrrolidone) Co-Electrospun Fibrous Membrane as a Tunable Quercetin Delivery Platform for Diabetic Wounds
Authors: Di Cristo Francesca , Valentino Anna , De Luca Ilenia , Peluso Gianfranco , Bonadies Irene , Di Salle Anna , Calarco Anna
Published: March 2023

Diabetic wound infections (DWI) represent one of the most costly and disruptive complications in diabetic mellitus. The hyperglycemic state induces a persistent inflammation with immunological and biochemical impairments that promotes delayed wound healing processes and wound infection that often results in extended hospitalization and limb amputations. Currently, the available therapeutic options for the management of DWI are excruciating and expensive. Hence, it is essential to develop and improve DWI-specific therapies able to intervene on multiple fronts. Quercetin (QUE) exhibits excellent anti-inflammatory, antioxidant, antimicrobial and wound healing properties, which makes it a promising molecule for the management of diabetic wounds. In the present study, Poly-lactic acid/poly(vinylpyrrolidone) (PP) co-electrospun fibers loaded with QUE were developed. The results demonstrated a bimodal diameter distribution with contact angle starting from 120°/127° and go to 0° in less than 5 s indicating the hydrophilic nature of fabricated samples. The release QUE kinetics, analyzed in simulated wound fluid (SWF), revealed a strong initial burst release, followed by a constant and continuous QUE release. Moreover, QUE-loaded membranes present excellent antibiofilm and anti-inflammatory capacity and significantly reduce the gene expression of M1 markers tumor necrosis factor (TNF)-α, and IL-1β in differentiated macrophages. In conclusion, the results suggested that the prepared mats loaded with QUE could be a hopeful drug-delivery system for the effective treatment of diabetic wound infections.
Tumor Spheroids as Model to Design Acoustically Mediated Drug Therapies: A Review
Authors: Roy Marie , Alix Corentin , Bouakaz Ayache , Serrière Sophie , Escoffre Jean-Michel
Published: March 2023

Tumor spheroids as well as multicellular tumor spheroids (MCTSs) are promising 3D in vitro tumor models for drug screening, drug design, drug targeting, drug toxicity, and validation of drug delivery methods. These models partly reflect the tridimensional architecture of tumors, their heterogeneity and their microenvironment, which can alter the intratumoral biodistribution, pharmacokinetics, and pharmacodynamics of drugs. The present review first focuses on current spheroid formation methods and then on in vitro investigations exploiting spheroids and MCTS for designing and validating acoustically mediated drug therapies. We discuss the limitations of the current studies and future perspectives. Various spheroid formation methods enable the easy and reproducible generation of spheroids and MCTSs. The development and assessment of acoustically mediated drug therapies have been mainly demonstrated in spheroids made up of tumor cells only. Despite the promising results obtained with these spheroids, the successful evaluation of these therapies will need to be addressed in more relevant 3D vascular MCTS models using MCTS-on-chip platforms. These MTCSs will be generated from patient-derived cancer cells and nontumor cells, such as fibroblasts, adipocytes, and immune cells.
Chitosan-Based Biomaterials for Tissue Regeneration
Authors: Kim Yevgeniy , Zharkinbekov Zharylkasyn , Raziyeva Kamila , Tabyldiyeva Laura , Berikova Kamila , Zhumagul Dias , Temirkhanova Kamila , Saparov Arman
Published: March 2023

Chitosan is a chitin-derived biopolymer that has shown great potential for tissue regeneration and controlled drug delivery. It has numerous qualities that make it attractive for biomedical applications such as biocompatibility, low toxicity, broad-spectrum antimicrobial activity, and many others. Importantly, chitosan can be fabricated into a variety of structures including nanoparticles, scaffolds, hydrogels, and membranes, which can be tailored to deliver a desirable outcome. Composite chitosan-based biomaterials have been demonstrated to stimulate in vivo regeneration and the repair of various tissues and organs, including but not limited to, bone, cartilage, dental, skin, nerve, cardiac, and other tissues. Specifically, de novo tissue formation, resident stem cell differentiation, and extracellular matrix reconstruction were observed in multiple preclinical models of different tissue injuries upon treatment with chitosan-based formulations. Moreover, chitosan structures have been proven to be efficient carriers for medications, genes, and bioactive compounds since they can maintain the sustained release of these therapeutics. In this review, we discuss the most recently published applications of chitosan-based biomaterials for different tissue and organ regeneration as well as the delivery of various therapeutics.
Relevance of the Extraction Stage on the Anti-Inflammatory Action of Fucoidans
Authors: Flórez-Fernández Noelia , Vaamonde-García Carlos , Torres Maria Dolores , Buján Manuela , Muíños Alexandra , Muiños Antonio , Lamas-Vázquez María J. , Meijide-Faílde Rosa , Blanco Francisco J. , Domínguez Herminia
Published: March 2023

The anti-inflammatory action of fucoidans is well known, based on both in vitro and some in vivo studies. The other biological properties of these compounds, their lack of toxicity, and the possibility of obtaining them from a widely distributed and renewable source, makes them attractive novel bioactives. However, fucoidans’ heterogeneity and variability in composition, structure, and properties depending on seaweed species, biotic and abiotic factors and processing conditions, especially during extraction and purification stages, make it difficult for standardization. A review of the available technologies, including those based on intensification strategies, and their influence on fucoidan composition, structure, and anti-inflammatory potential of crude extracts and fractions is presented.
System Analysis Based on Lipid-Metabolism-Related Genes Identifies AGT as a Novel Therapy Target for Gastric Cancer with Neoadjuvant Chemotherapy
Authors: Zhu Le , Ma Ming , Zhang Lumin , Wang Shun , Guo Yu , Ling Xinxin , Lin Hanchao , Lai Nannan , Lin Shengli , Du Ling , Dong Qiongzhu
Published: March 2023

Gastric cancer (GC) is one of the most common causes of cancer-related deaths worldwide, and chemotherapy is still a standard strategy for treating patients with advanced GC. Lipid metabolism has been reported to play an important role in the carcinogenesis and development of GC. However, the potential values of lipid-metabolism-related genes (LMRGs) concerning prognostic value and the prediction of chemotherapy responsiveness in GC remains unclear. A total of 714 stomach adenocarcinoma patients were enrolled from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. Using univariate Cox and LASSO regression analyses, we developed a risk signature based on LMRGs that can distinguish high-GC-risk patients from low-risk patients with significant differences in overall survival. We further validated this signature prognostic value using the GEO database. The R package “pRRophetic” was applied to calculate the sensitivity of each sample from high- and low-risk groups to chemotherapy drugs. The expression of two LMRGs, AGT and ENPP7, can predict the prognosis and response to chemotherapy in GC. Furthermore, AGT significantly promoted GC growth and migration, and the downregulation of AGT enhanced the chemotherapy response of GC both in vitro and in vivo. Mechanistically, AGT induced significant levels of epithelial–mesenchymal transition (EMT) through the PI3K/AKT pathway. The PI3K/AKT pathway agonist 740 Y-P can restore the EMT of GC cells impaired by AGT knockdown and treatment with 5-fluorouracil. Our findings suggest that AGT plays a key role in the development of GC, and targeting AGT may help to improve the chemotherapy response of GC patients.
Radioimmune Imaging of α4β7 Integrin and TNFα for Diagnostic and Therapeutic Applications in Inflammatory Bowel Disease
Authors: Signore Alberto , Bonfiglio Rita , Varani Michela , Galli Filippo , Campagna Giuseppe , Desco Manuel , Cussó Lorena , Mattei Maurizio , Wunder Andreas , Borri Filippo , Lupo Maria T. , Bonanno Elena
Published: March 2023

Imaging using radiolabelled monoclonal antibodies can provide, non-invasively, molecular information which allows for the planning of the best treatment and for monitoring the therapeutic response in cancer, as well as in chronic inflammatory diseases. In the present study, our main goal was to evaluate if a pre-therapy scan with radiolabelled anti-α4β7 integrin or radiolabelled anti-TNFα mAb could predict therapeutic outcome with unlabelled anti-α4β7 integrin or anti-TNFα mAb. To this aim, we developed two radiopharmaceuticals to study the expression of therapeutic targets for inflammatory bowel diseases (IBD), to be used for therapy decision making. Both anti-α4β7 integrin and anti-TNFα mAbs were successfully radiolabelled with technetium-99m with high labelling efficiency and stability. Dextran sulfate sodium (DSS)-induced colitis was used as a model for murine IBD and the bowel uptake of radiolabelled mAbs was evaluated ex vivo and in vivo by planar and SPECT/CT images. These studies allowed us to define best imaging strategy and to validate the specificity of mAb binding in vivo to their targets. Bowel uptake in four different regions was compared to immunohistochemistry (IHC) score (partial and global). Then, to evaluate the biomarker expression prior to therapy administration, in initial IBD, another group of DSS-treated mice was injected with radiolabelled mAb on day 2 of DSS administration (to quantify the presence of the target in the bowel) and then injected with a single therapeutic dose of unlabelled anti-α4β7 integrin or anti-TNFα mAb. Good correlation was demonstrated between bowel uptake of radiolabelled mAb and immunohistochemistry (IHC) score, both in vivo and ex vivo. Mice treated with unlabelled α4β7 integrin and anti-TNFα showed an inverse correlation between the bowel uptake of radiolabelled mAb and the histological score after therapy, proving that only mice with high α4β7 integrin or TNFα expression will benefit of therapy with unlabelled mAb.
Studies on Cistanches Herba: A Bibliometric Analysis
Authors: Wu Longjiang , Xiang Tian , Chen Chen , Isah Murtala Bindawa , Zhang Xiaoying
Published: March 2023

As a famous tonic herb, Cistanches Herba is known for its broad medicinal functions, especially its hormone balancing, anti-aging, anti-dementia, anti-tumor, anti-oxidative, neuroprotective, and hepatoprotective effects. This study aims to provide a comprehensive bibliometric analysis of studies on Cistanche and to identify research hotspots and frontier topics on the genus. Based on the metrological analysis software CiteSpace, 443 Cistanche related papers were quantitatively reviewed. The results indicate that 330 institutions from 46 countries have publications in this field. China was the leading country in terms of research importance and number of publication (335 articles). In the past decades, studies on Cistanche have mainly focused on its rich active substances and pharmacological effects. Although the research trend shows that Cistanche has grown from an endangered species to an important industrial plant, its breeding and cultivation continue to be important areas for research. In the future, the application of Cistanche species as functional foods may be a new research trend. In addition, active collaborations among researchers, institutions, and countries are expected.
Miniature Inverted-Repeat Transposable Elements: Small DNA Transposons That Have Contributed to Plant MICRORNA Gene Evolution
Authors: Pegler Joseph L. , Oultram Jackson M. J. , Mann Christopher W. G. , Carroll Bernard J. , Grof Christopher P. L. , Eamens Andrew L.
Published: March 2023

Angiosperms form the largest phylum within the Plantae kingdom and show remarkable genetic variation due to the considerable difference in the nuclear genome size of each species. Transposable elements (TEs), mobile DNA sequences that can amplify and change their chromosome position, account for much of the difference in nuclear genome size between individual angiosperm species. Considering the dramatic consequences of TE movement, including the complete loss of gene function, it is unsurprising that the angiosperms have developed elegant molecular strategies to control TE amplification and movement. Specifically, the RNA-directed DNA methylation (RdDM) pathway, directed by the repeat-associated small-interfering RNA (rasiRNA) class of small regulatory RNA, forms the primary line of defense to control TE activity in the angiosperms. However, the miniature inverted-repeat transposable element (MITE) species of TE has at times avoided the repressive effects imposed by the rasiRNA-directed RdDM pathway. MITE proliferation in angiosperm nuclear genomes is due to their preference to transpose within gene-rich regions, a pattern of transposition that has enabled MITEs to gain further transcriptional activity. The sequence-based properties of a MITE results in the synthesis of a noncoding RNA (ncRNA), which, after transcription, folds to form a structure that closely resembles those of the precursor transcripts of the microRNA (miRNA) class of small regulatory RNA. This shared folding structure results in a MITE-derived miRNA being processed from the MITE-transcribed ncRNA, and post-maturation, the MITE-derived miRNA can be used by the core protein machinery of the miRNA pathway to regulate the expression of protein-coding genes that harbor homologous MITE insertions. Here, we outline the considerable contribution that the MITE species of TE have made to expanding the miRNA repertoire of the angiosperms.
Cytogeography of Naturalized Solidago canadensis Populations in Europe
Authors: Tian Zhongsai , Cheng Jiliang , Xu Jingxuan , Feng Dongyan , Zhong Jian , Yuan Xiaoxiao , Zhang Zheng , Zhang Yu , Mao Zhiyuan , Qiang Sheng
Published: March 2023

Autopolyploidization has driven the successful invasion of Solidago canadensis in East Asia. However, it was believed that only diploid S. canadensis invaded Europe, whereas polyploids never did. Here, molecular identification, ploidy level, and morphological traits of ten S. canadensis populations collected in Europe were compared with previously identified S. canadensis populations from other continents and S. altissima populations. Furthermore, the ploidy-driven geographical differentiation pattern of S. canadensis in different continents was investigated. All ten European populations were identified as S. canadensis with five diploid and five hexaploid populations. Significant differences in morphological traits existed among diploids and polyploids (tetraploids and hexaploids), rather than between polyploids from different introduced ranges and between S. altissima and polyploidy S. canadensis. The invasive hexaploids and diploids had few differences in latitudinal distributions in Europe, which was similar to the native range but different from a distinct climate-niche differentiation in Asia. This may be attributed to the bigger difference in climate between Asia and Europe and North America. The morphological and molecular evidences proved the invasion of polyploid S. canadensis in Europe and suggest that S. altissima may be merged into a complex of S. canadensis species. Our study may be concluded that geographical and ecological niche differentiation of an invasive plant driven by ploidy depends on the degree of difference in the environmental factors between the introduced and native range, which provides new insight into the invasive mechanism.
Enhancement of Salinity Stress Tolerance in Lettuce (Lactuca sativa L.) via Foliar Application of Nitric Oxide
Authors: Sardar Hasan , Khalid Zubair , Ahsan Muhammad , Naz Safina , Nawaz Aamir , Ahmad Riaz , Razzaq Kashif , Wabaidur Saikh M. , Jacquard Cédric , Širić Ivan , Kumar Pankaj , Abou Fayssal Sami
Published: March 2023

Salt stress negatively affects the growth, development, and yield of horticultural crops. Nitric oxide (NO) is considered a signaling molecule that plays a key role in the plant defense system under salt stress. This study investigated the impact of exogenous application of 0.2 mM of sodium nitroprusside (SNP, an NO donor) on the salt tolerance and physiological and morphological characteristics of lettuce (Lactuca sativa L.) under salt stress (25, 50, 75, and 100 mM). Salt stress caused a marked decrease in growth, yield, carotenoids and photosynthetic pigments in stressed plants as compared to control ones. Results showed that salt stress significantly affected the oxidative compounds (superoxide dismutase (SOD), peroxidase (POD), catalase (CAT) and ascorbate peroxidase (APX)) and non-oxidative compounds (ascorbic acid, total phenols, malondialdehyde (MDA), proline, and H2O2) in lettuce. Moreover, salt stress decreased nitrogen (N), phosphorous (P), and potassium ions (K+) while increasing Na ions (Na+) in the leaves of lettuce under salt stress. The exogenous application of NO increased ascorbic acid, total phenols, antioxidant enzymes (SOD, POD, CAT, and APX) and MDA content in the leaves of lettuce under salt stress. In addition, the exogenous application of NO decreased H2O2 content in plants under salt stress. Moreover, the exogenous application of NO increased leaf N in control, and leaf P and leaf and root K+ content in all treatments while decreasing leaf Na+ in salt-stressed lettuce plants. These results provide evidence that the exogenous application of NO on lettuce helps mitigate salt stress effects.
Effect of Inoculum Size and Age, and Sucrose Concentration on Cell Growth to Promote Metabolites Production in Cultured Taraxacum officinale (Weber) Cells
Authors: Martínez María Eugenia , Jorquera Lorena , Poirrier Paola , Díaz Katy , Chamy Rolando
Published: March 2023

Pentacyclic triterpenes, including lupeol, α- amyrin, and β-amyrin, present a large range of biological activities including anti-inflammatory, anti-cancer, and gastroprotective properties. The phytochemistry of dandelion (Taraxacum officinale) tissues has been widely described. Plant biotechnology offers an alternative for secondary metabolite production and several active plant ingredients are already synthesized through in vitro cultures. This study aimed to establish a suitable protocol for cell growth and to determine the accumulation of α-amyrin and lupeol in cell suspension cultures of T. officinale under different culture conditions. To this end, inoculum density (0.2% to 8% (w/v)), inoculum age (2- to 10-week-old), and carbon source concentration (1%, 2.3%, 3.2%, and 5.5% (w/v)) were investigated. Hypocotyl explants of T. officinale were used for callus induction. Age, size, and sucrose concentrations were statistically significant in cell growth (fresh and dry weight), cell quality (aggregation, differentiation, viability), and triterpenes yield. The best conditions for establishing a suspension culture were achieved by using a 6-week-old callus at 4% (w/v) and 1% (w/v) of sucrose concentration. Results indicate that 0.04 (±0.02) α-amyrin and 0.03 (±0.01) mg/g lupeol can be obtained in suspension culture under these starting conditions at the 8th week of culture. The results of the present study provide a backdrop for future studies in which an elicitor could be incorporated to increase the large-scale production of α-amyrin and lupeol from T. officinale.
Moonlight Is Perceived as a Signal Promoting Genome Reorganization, Changes in Protein and Metabolite Profiles and Plant Growth
Authors: Singiri Jeevan R. , Priyanka Govindegowda , Trishla Vikas S. , Adler-Agmon Zachor , Grafi Gideon
Published: March 2023

Rhythmic exposure to moonlight has been shown to affect animal behavior, but its effects on plants, often observed in lunar agriculture, have been doubted and often regarded as myth. Consequently, lunar farming practices are not well scientifically supported, and the influence of this conspicuous environmental factor, the moon, on plant cell biology has hardly been investigated. We studied the effect of full moonlight (FML) on plant cell biology and examined changes in genome organization, protein and primary metabolite profiles in tobacco and mustard plants and the effect of FML on the post-germination growth of mustard seedlings. Exposure to FML was accompanied by a significant increase in nuclear size, changes in DNA methylation and cleavage of the histone H3 C-terminal region. Primary metabolites associated with stress were significantly increased along with the expression of stress-associated proteins and the photoreceptors phytochrome B and phototropin 2; new moon experiments disproved the light pollution effect. Exposure of mustard seedlings to FML enhanced growth. Thus, our data show that despite the low-intensity light emitted by the moon, it is an important environmental factor perceived by plants as a signal, leading to alteration in cellular activities and enhancement of plant growth.
Blue Photons from Broad-Spectrum LEDs Control Growth, Morphology, and Coloration of Indoor Hydroponic Red-Leaf Lettuce
Authors: Meng Qingwu , Runkle Erik S.
Published: March 2023

For indoor crop production, blue + red light-emitting diodes (LEDs) have high photosynthetic efficacy but create pink or purple hues unsuitable for workers to inspect crops. Adding green light to blue + red light forms a broad spectrum (white light), which is created by: phosphor-converted blue LEDs that cast photons with longer wavelengths, or a combination of blue, green, and red LEDs. A broad spectrum typically has a lower energy efficiency than dichromatic blue + red light but increases color rendering and creates a visually pleasing work environment. Lettuce growth depends on the interactions of blue and green light, but it is not clear how phosphor-converted broad spectra, with or without supplemental blue and red light, influence crop growth and quality. We grew red-leaf lettuce ‘Rouxai’ in an indoor deep-flow hydroponic system at 22 °C air temperature and ambient CO2. Upon germination, plants received six LED treatments delivering different blue fractions (from 7% to 35%) but the same total photon flux density (400 to 799 nm) of 180 μmol·m−2·s−1 under a 20 h photoperiod. The six LED treatments were: (1) warm white (WW180); (2) mint white (MW180); (3) MW100 + blue10 + red70; (4) blue20 + green60 + red100; (5) MW100 + blue50 + red30; and (6) blue60 + green60 + red60. Subscripts denote photon flux densities in μmol·m−2·s−1. Treatments 3 and 4 had similar blue, green, and red photon flux densities, as did treatments 5 and 6. At the harvest of mature plants, lettuce biomass, morphology, and color were similar under WW180 and MW180, which had different green and red fractions but similar blue fractions. As the blue fraction in broad spectra increased, shoot fresh mass, shoot dry mass, leaf number, leaf size, and plant diameter generally decreased and red leaf coloration intensified. Compared to blue + green + red LEDs, white LEDs supplemented with blue + red LEDs had similar effects on lettuce when they delivered similar blue, green, and red photon flux densities. We conclude that the blue photon flux density in broad spectra predominantly controls lettuce biomass, morphology, and coloration.
Floral Homeotic Factors: A Question of Specificity
Authors: Goslin Kevin , Finocchio Andrea , Wellmer Frank
Published: March 2023

MADS-domain transcription factors are involved in the control of a multitude of processes in eukaryotes, and in plants, they play particularly important roles during reproductive development. Among the members of this large family of regulatory proteins are the floral organ identity factors, which specify the identities of the different types of floral organs in a combinatorial manner. Much has been learned over the past three decades about the function of these master regulators. For example, it has been shown that they have similar DNA-binding activities and that their genome-wide binding patterns exhibit large overlaps. At the same time, it appears that only a minority of binding events lead to changes in gene expression and that the different floral organ identity factors have distinct sets of target genes. Thus, binding of these transcription factors to the promoters of target genes alone may not be sufficient for their regulation. How these master regulators achieve specificity in a developmental context is currently not well understood. Here, we review what is known about their activities and highlight open questions that need to be addressed to gain more detailed insights into the molecular mechanisms underlying their functions. We discuss evidence for the involvement of cofactors as well as the results from studies on transcription factors in animals that may be instructive for a better understanding of how the floral organ identity factors achieve regulatory specificity.
Performance Evaluation of Hot Mix Asphalt (HMA) Containing Polyethylene Terephthalate (PET) Using Wet and Dry Mixing Techniques
Authors: Agha Nisma , Hussain Arshad , Ali Agha Shah , Qiu Yanjun
Published: March 2023

This study evaluates the performance of Polyethylene Terephthalate (PET)-modified hot mix asphalt. Aggregate, bitumen of grade 60/70 and crushed plastic bottle waste were utilized in this study. Polymer Modified Bitumen (PMB) was prepared using a high shear laboratory type mixer rotating at a speed of 1100 rpm with varying PET content of 2%, 4%, 6%, 8% and 10%, respectively. Overall, the results of preliminary tests suggested that bitumen hardened with the addition of PET. Following optimum bitumen content determination, various modified and controlled HMA samples were prepared as per wet and dry mixing techniques. This research presents an innovative technique to compare the performance of HMA prepared via dry and wet mixing techniques. Performance evaluation tests, which include the Moisture Susceptibility Test (ALDOT-361-88), Indirect Tensile Fatigue Test (ITFT-EN12697-24) and Marshall Stability and Flow Tests (AASHTO T245-90), were conducted on controlled and modified HMA samples. The dry mixing technique yielded better results in terms of resistance against fatigue cracking, stability and flow; however, the wet mixing technique yielded better results in terms of resistance against moisture damage. The addition of PET at more than 4% resulted in a decreased trend for fatigue, stability and flow due to the stiffer nature of PET. However, for the moisture susceptibility test optimum PET content was noted to be 6%. Polyethylene Terephthalate-modified HMA is found to be the economical solution for high volume road construction and maintenance, besides having other significant advantages such as increased sustainability and waste reduction.