bluuebunny/crossref_metadata_2025 huggingface dataset:
Histidine Enhances the Anticancer Effect of Gemcitabine against Pancreatic Cancer via Disruption of Amino Acid Homeostasis and Oxidant—Antioxidant Balance
Authors: Kumar Narendra , Rachagani Satyanarayana , Natarajan Gopalakrishnan , Crook Alexandra , Gopal Thiyagarajan , Rajamanickam Vinothkumar , Kaushal Jyoti B. , Nagabhishek Sirpu N. , Powers Robert , Batra Surinder K. , Saraswathi Viswanathan
Published: May 2023

Due to the severe toxicity posed by chemotherapeutic drugs, adjuvant nutritional intervention has gained increased attention in the treatment of pancreatic cancer (PC). Amino acid (AA) metabolism is aberrantly regulated in PC and circulating histidine (His) levels are low in PC patients. We hypothesized that His uptake and/or metabolism is dysregulated in PC and that combining His with gemcitabine (Gem), a drug used in the treatment of PC, will enhance the anti-cancer effects of Gem. We performed in vitro and in vivo studies to determine the anticancer effect of the combination of His and Gem against lethal PC. We demonstrate that circulating His levels are low in both human subjects and genetically engineered mice exhibiting pancreatic tumors. Interestingly, the expression of histidine ammonia lyase, an enzyme involved in His catabolism, is higher in PC compared to normal subjects. His + Gem exerts a more potent cytotoxic effect in PC cells compared to individual treatments. His treatment results in a profound increase in His accumulation, accompanied by a depletion of a number of AAs, promoting cancer cell survival and/or glutathione (GSH) synthesis. His but not Gem increases hydrogen peroxide and depletes cellular GSH. Supplementation with GSH protects cells against His + Gem-induced cytotoxicity. Further, our in vivo studies demonstrate that His + Gem potently reduced tumor mass and improved mouse survival. Taken together, our data suggest that PC cells exhibit an aberrant His uptake/accumulation which, in turn, leads to oxidative stress and depletion of AA pool, thereby enhancing the anticancer effect of Gem.
Long-Term Treatment with Gadopentetic Acid or Gadodiamide Increases TRPC5 Expression and Decreases Adriamycin Nuclear Accumulation in Breast Cancer Cells
Authors: Zhang Weiheng , Wang Mengyuan , Lv Weizhen , White Fletcher A. , Chen Xingjuan , Obukhov Alexander G.
Published: May 2023

Gadopentetic acid and gadodiamide are paramagnetic gadolinium-based contrast agents (GBCAs) that are routinely used for dynamic contrast-enhanced magnetic resonance imaging (MRI) to monitor disease progression in cancer patients. However, growing evidence indicates that repeated administration of GBCAs may lead to gadolinium (III) cation accumulation in the cortical bone tissue, skin, basal ganglia, and cerebellum, potentially leading to a subsequent slow long-term discharge of Gd3+. Gd3+ is a known activator of the TRPC5 channel that is implicated in breast cancer’s resistance to chemotherapy. Herein, we found that gadopentetic acid (Gd-DTPA, 1 mM) potentiated the inward and outward currents through TRPC5 channels, which were exogenously expressed in HEK293 cells. Gd-DTPA (1 mM) also activated the Gd3+-sensitive R593A mutant of TRPC5, which exhibits a reduced sensitivity to GPCR-Gq/11-PLC dependent gating. Conversely, Gd-DTPA had no effect on TRPC5-E543Q, a Gd3+ insensitive TRPC5 mutant. Long-term treatment (28 days) of human breast cancer cells (MCF-7 and SK-BR-3) and adriamycin-resistant MCF-7 cells (MCF-7/ADM) with Gd-DTPA (1 mM) or gadodiamide (GDD, 1 mM) did not affect the IC50 values of ADM. However, treatment with Gd-DTPA or GDD significantly increased TRPC5 expression and decreased the accumulation of ADM in the nuclei of MCF-7 and SK-BR-3 cells, promoting the survival of these two breast cancer cells in the presence of ADM. The antagonist of TRPC5, AC1903 (1 μM), increased ADM nuclear accumulation induced by Gd-DTPA-treatment. These data indicate that prolonged GBCA treatment may lead to increased breast cancer cell survival owing to the upregulation of TRPC5 expression and the increased ADM resistance. We propose that while focusing on providing medical care of the best personalized quality in the clinic, excessive administration of GBCAs should be avoided in patients with metastatic breast cancer to reduce the risk of promoting breast cancer cell drug resistance.
Exploring the Therapeutic Potential of Elastase Inhibition in Age-Related Macular Degeneration in Mouse and Human
Authors: Navneet Soumya , Brandon Carlene , Simpson Kit , Rohrer Bärbel
Published: May 2023

Abnormal turnover of the extracellular matrix (ECM) protein elastin has been linked to AMD pathology. Elastin is a critical component of Bruch’s membrane (BrM), an ECM layer that separates the retinal pigment epithelium (RPE) from the underlying choriocapillaris. Reduced integrity of BrM’s elastin layer corresponds to areas of choroidal neovascularization (CNV) in wet AMD. Serum levels of elastin-derived peptides and anti-elastin antibodies are significantly elevated in AMD patients along with the prevalence of polymorphisms of genes regulating elastin turnover. Despite these results indicating significant associations between abnormal elastin turnover and AMD, very little is known about its exact role in AMD pathogenesis. Here we report on results that suggest that elastase enzymes could play a direct role in the pathogenesis of AMD. We found significantly increased elastase activity in the retinas and RPE cells of AMD mouse models, and AMD patient-iPSC-derived RPE cells. A1AT, a protease inhibitor that inactivates elastase, reduced CNV lesion sizes in mouse models. A1AT completely inhibited elastase-induced VEGFA expression and secretion, and restored RPE monolayer integrity in ARPE-19 monolayers. A1AT also mitigated RPE thickening, an early AMD phenotype, in HTRA1 overexpressing mice, HTRA1 being a serine protease with elastase activity. Finally, in an exploratory study, examining archival records from large patient data sets, we identified an association between A1AT use, age and AMD risk. Our results suggest that repurposing A1AT may have therapeutic potential in modifying the progression to AMD.
Theoretical Basis for the Photoelastic Residual Stress Evaluation in Misaligned Cubic Crystals
Authors: Davì Fabrizio , Rinaldi Daniele , Montalto Luigi
Published: May 2023

Photoelasticity is a fast and powerful technique for internal stress detection and quality control in crystals; to fully exploit its possibilities, an appropriate theoretical analysis must be developed for different crystallographic structure and observation planes. For a cubic crystal specimen whose geometry is non-coherent with its crystallographic directions (i.e., observation planes and crystallographic directions are not parallel), we write a set of equations that allow an estimate of the refraction indices as a function of the residual stress. This is obtained upon the assumption that the residual stress may be represented by a plane stress parallel to the observation face. For cubic crystals, we obtain an explicit estimate of the residual stress intensity; this can be achieved provided we know the piezo-optic tensor component, the orientation of two non-parallel specimen faces with respect to the crystallographic axes, and that we can measure the principal directions of the refractive indices on the observation face.
Genetic Variability and Family Relationships in a Reintroduced Osprey (Pandion haliaetus) Population: A Field-Lab Integrated Approach
Authors: Monti Flavio , Mengoni Chiara , Sforzi Andrea , Pezzo Francesco , Serra Lorenzo , Sammuri Giampiero , Mucci Nadia
Published: May 2023

Reintroductions represent an opportunity to restore local biodiversity and reverse the effect of taxa extinction. However, they need feasibility and monitoring plans before and during their implementation to ensure concrete and lasting results. During the 20th century, the osprey (Pandion haliaetus) underwent a severe population decline in many European countries due to direct persecution and coast exploitation. In the 1960s–1970s, it was declared extinct as a breeder in Italy. In 2004, the Maremma Regional Park (Tuscany, central Italy) started a reintroduction project by capturing and releasing, from 2006 to 2010, 33 juvenile Corsican ospreys on the southern coast of Tuscany. The settlement of the first breeding pair in 2011 was the initial sign of the success of the reintroduction project, then further pairs settled from 2011 onward. A total of 81 feather or blood samples were collected for DNA extraction from both translocated (2006–2010) and newborn individuals (2011–2021). Individuals were analyzed at 16 microsatellite loci to verify any changes in genetic variability over time and to set out a protocol for the reconstruction of kinship for conservation and management purposes. We did not observe a reduction in genetic variability between the two sampling periods, although we found a slight sign of the founder effect in the reestablished population. A strong genetic differentiation was observed between this Mediterranean population and an injured osprey from a Northern European population, thus confirming the importance of considering the local genetic pool in any reintroduction project. Monogamous behavior was confirmed by family reconstruction, which allowed the identification of clear kinship relationships. Our findings indirectly inform on the genetic variability of the population during the 16-year period from the start of the project and provide useful insights for its long-term conservation.
Faunistic and Structural Changes in Shallow Coastal Benthic Communities of the Ebre Delta (NW Mediterranean Sea)
Authors: Ramón Montserrat , Marco-Herrero Elena , Galimany Eve , Recasens Laura , Abelló Pere
Published: May 2023

The Ebre Delta (NW Mediterranean), which is considered a highly vulnerable ecosystem, is one of the most important European wetlands and belongs to the Natura 2000 network. The present study aims to characterize the benthic megainvertebrate communities inhabiting the Ebre Delta soft-bottom infralittoral to acquire faunistic and biological knowledge for two periods of time, 23 years apart. Experimental trawls were conducted during the two periods (1992–1993 and 2016–2017) in three depth strata, between 5 and 25 m. A total of 139 and 170 taxa were collected at each period, respectively. Our results showed that community species composition and structure varied between periods and among depth strata. Overall, a large decrease in density and biomass was detected for most species in all three depth strata examined (0–5, 15–20, and 20–25 m) in 2016–2017, especially in the shallowest stratum. Species richness was higher in 2016–2017 than in 1992–1993, and the lowest values were found at the shallowest stratum in both periods. The significant biomass losses herein reported highlight the need to increase, in time and effort, the monitoring of large marine invertebrates in coastal areas, where many taxa provide important ecosystem functions and services.
Microbial Community and Enzyme Activity of Forest Plantation, Natural Forests, and Agricultural Land in Chilean Coastal Cordillera Soils
Authors: Rivas Yessica , Aponte Humberto , Rivera-Salazar Diego , Matus Francisco , Martínez Oscar , Encina Carolina , Retamal-Salgado Jorge
Published: May 2023

Despite the global expansion of forest plantations in Chile, their effect on biology properties of soil has still been only scarcely studied. Land use change in the Chilean Coastal Cordillera (36° to 40° S) is mainly attributed to the conversion of native forest to agriculture and forest plantations (Eucalyptus globulus and Pinus radiata de Don). The aim of this paper was to evaluate the changes in microbial composition (PCR-DGGE) and enzyme activity after the substitution of a native forest (e.g., Nothofagus spp.) by fast-growing exotic species and cropping. The most important factors that influence the abundance and diversity of bacteria and the fungi community were the soil organic matter (SOM) content, phosphorous (P-Olsen), calcium (Ca), boron (B), and water-holding capacity. These variables can better predict the microbial community composition and its enzymatic activity in the surface Ah horizon. Land use change also affected chemical soil properties of biogeochemical cycles. However, to deeply understand the connection between chemical and physical soil factors and microbial community composition, more research is needed. On the other hand, the expansion of forest plantations in Chile should be subject to legislation aimed to protect the biological legacy as a strategy for forest productivity as well as the soil microbial biodiversity.
Microevolutionary Processes in a Foundation Tree Inform Macrosystem Patterns of Community Biodiversity and Structure
Authors: Bothwell Helen M. , Keith Arthur R. , Cooper Hillary F. , Hull Julia B. , Andrews Lela V. , Wehenkel Christian , Hultine Kevin R. , Gehring Catherine A. , Cushman Samuel A. , Whitham Thomas G. , Allan Gerard J.
Published: May 2023

Despite an increased focus on multiscale relationships and interdisciplinary integration, few macroecological studies consider the contribution of genetic-based processes to landscape-scale patterns. We test the hypothesis that tree genetics, climate, and geography jointly drive continental-scale patterns of community structure, using genome-wide SNP data from a broadly distributed foundation tree species (Populus fremontii S. Watson) and two dependent communities (leaf-modifying arthropods and fungal endophytes) spanning southwestern North America. Four key findings emerged: (1) Tree genetic structure was a significant predictor for both communities; however, the strength of influence was both scale- and community-dependent. (2) Tree genetics was the primary driver for endophytes, explaining 17% of variation in continental-scale community structure, whereas (3) climate was the strongest predictor of arthropod structure (24%). (4) Power to detect tree genotype—community phenotype associations changed with scale of genetic organization, increasing from individuals to populations to ecotypes, emphasizing the need to consider nonstationarity (i.e., changes in the effects of factors on ecological processes across scales) when inferring macrosystem properties. Our findings highlight the role of foundation tree species as drivers of macroscale community structure and provide macrosystems ecology with a theoretical framework for linking fine- and intermediate-scale genetic processes to landscape-scale patterns. Management of the genetic diversity harbored within foundation species is a critical consideration for conserving and sustaining regional biodiversity.
The “Oxygen Sink” of Bamboo Shoots Regulates and Guarantees the Oxygen Supply for Aerobic Respiration
Authors: Huang Manchang , Zhao Aoshun , Ding Xingcui , Li Jian , Zhang Jiajia , Ma Ruixiang , Xiao Zizhang , Cai Hanjiang , Wang Anke , Bi Yufang
Published: May 2023

The amazingly rapid growth of bamboo shoots requires strong respiration and provides a large amount of energy and intermediate metabolites. Strong aerobic respiration requires a large amount of O2. This raises the following question: What is the source and mechanism of O2 supply to meet aerobic respiration? However, currently, this remains unknown. The underground buds (US), the 2-m-high overground buds (AS), and the 8-m-high growth arrest buds (HS) of bamboo (Phyllostachys prominens) were collected to represent their different stages of growth and development. The fifth bamboo shoot node at each stage was sealed by two membranes, and treated in a polyethylene zip-lock bag filled with air (21% O2 + 79% N2) and nitrogen (100% N2) for 1.5 h. The concentrations of free O2 and CO2 in the shoot cavities in polyethylene zip-lock bags, and the ethanol content in the shoot body before and after treatment were determined. In addition, the photosynthetic rates of the fifth bamboo internodes of 1 y/o, 2 y/o and 3 y/o bamboo in the field were measured. The results indicated that: (1) When treated with air and nitrogen, US, AS and HS mainly exhibited aerobic respiration, and there was almost no anaerobic respiration; (2) When treated with air, 59.66%, 54.47% and 45.84% of the O2 in the aerobic respiration of US, AS and HS came from the polyethylene zip-lock bag, 0.06%, 0.57% and 0.650% came from the shoot cavity, but 40.28%, 44.96% and 53.51% of the O2 was of an unknown source; (3) Treated by nitrogen, 0.19%, 4.71% and 4.79% of O2 in aerobic respiration of US, AS and HS came from shoot cavity, while the other 99.808%, 95.290% and 95.21% of O2 came from unknown sources; and (4) The photosynthesis of the fifth internodes of 1 y/o, 2 y/o and 3 y/o bamboo generated little oxygen that could not absolutely meet the huge O2 supply for aerobic respiration. It was concluded that the respiration of P. prominens shoots in its different growth and development stages was dominated by aerobic respiration. O2 supply pathways were mainly via the sheath stomata; however, there was little absorption from dissolved O2 in the soil water and little supply produced by shoot/stem photosynthesis. It was found that the large supply of oxygen in the aerobic respiration of bamboo shoots and young bamboo was of an unknown source under air treatment and nitrogen treatment, i.e., 40.28%–53.51% and 95.21%–99.81% of oxygen in the aerobic respiration of bamboo shoots and young bamboo was of unknown origin, respectively. Therefore, we proposed that bamboo shoots may exhibit the phenomenon of acting as an “oxygen sink”, which can provide a large amount of O2 from unknown sources to ensure the rapid growth of bamboo shoots and young bamboo.
Reference Values, Determinants and Regression Equation for the Timed-Up and Go Test (TUG) in Healthy Asian Population Aged 21 to 85 Years
Authors: Tan Teck Chye , Guo Yan Y. , Ho Dilys J. , Sanwari Nur Aidah Binti , Quek Patricia H. , Tan Rachel S. , Yap Felicia S. , Yang Mingxing , Yeung Meredith T.
Published: May 2023

The “Timed-Up-and-Go” test (TUG) is a standard assessment tool for functional mobility as it assesses several functional components, including balance, gait, and lower-extremity strength. It has good reliability and validity and is cost-effective and safe, making it an ideal screening tool for falls in various populations, such as older adults or various conditions. However, TUG interpretation relies on comparisons against local normative reference values (NRV), which few studies established for the Asian or younger population. Hence, this study aims to: (1) establish the normative reference values NRV for the population aged 21 to 85 years; (2) determine demographic and anthropometric variables that influence the TUG results; and (3) establish the regression equation of the TUG. A prospective, convenience sampling cross-sectional study recruited subjects aged 21–85 from the community to complete two TUG trials in various parts of Singapore. Variables collected include gender, age, height (meters, m), weight (kilograms, kg), and hand grip strength (HGS) (kg). The intraclass correlation coefficient (ICC) and 95% confidence interval (95% CI) determined test-retest, intra- and inter-rater reliabilities. TUG and variables were analyzed with descriptive statistics and multiple linear regression. p < 0.05 was accepted as statistical significance. Further, 838 subjects (542 females, 296 males) completed the data collection. The mean TUG time was 9.16 s (95% CI 9.01–9.3). Slower TUG was observed with advanced age and female gender. Multiple linear regression analysis demonstrated that age, height, and weight were the best variables to predict TUG scores. The regression formula presented as: TUG (second) = 9.11 + 0.063 (Age, years)—3.19 (Height, meters) + 0.026 (Weight, Kilograms) (R2 = 0.374, p < 0.001). This study provided the TUG NRV and regression formula for healthy Asian adults aged 21 to 85. The information may provide a quick reference for the physical function to interpret assessment findings and guide decision-making in various health and healthcare settings.
Subjective Happiness, Frequency of Laughter, and Hypertension: A Cross-Sectional Study Based on the Japan Gerontological Evaluation Study (JAGES)
Authors: Hayashi Fumikazu , Shirai Yuka , Ohira Tetsuya , Shirai Kokoro , Kondo Naoki , Kondo Katsunori
Published: May 2023

In recent years, positive psychological factors, such as subjective happiness and laughter, have been reported to be associated with cardiovascular disease. In this study, we examined the relationship of hypertension with subjective happiness and frequency of laughter using the data from the Japan Gerontological Evaluation Study (JAGES). Of the 138,294 respondents, 26,368 responded to a version of the self-administered questionnaire that included a question about the frequency of laughter in the JAGES 2013. In total, 22,503 (10,571 men and 11,932 women) were included in the analysis after excluding those with missing responses regarding a history of hypertension, frequency of laughter, and subjective happiness. The prevalence of hypertension in this study was 10,364 (46.1%). Multivariate logistic regression analysis showed that age, female sex, obesity, infrequent chewing, former and current drinker, seeing three to five friends, and the absence of hobbies were positively associated with hypertension. However, infrequent laughter/high level of subjective happiness, frequent laughter/high level of subjective happiness, being underweight, and current smoker were negatively associated with hypertension. As per the findings of this study, it was determined that subjective happiness was negatively associated with hypertension. Therefore, this study suggests that having more opportunities to feel happiness may be important in preventing hypertension.
Improving Semantic Information Retrieval Using Multinomial Naive Bayes Classifier and Bayesian Networks
Authors: Chebil Wiem , Wedyan Mohammad , Alazab Moutaz , Alturki Ryan , Elshaweesh Omar
Published: May 2023

This research proposes a new approach to improve information retrieval systems based on a multinomial naive Bayes classifier (MNBC), Bayesian networks (BNs), and a multi-terminology which includes MeSH thesaurus (Medical Subject Headings) and SNOMED CT (Systematized Nomenclature of Medicine of Clinical Terms). Our approach, which is entitled improving semantic information retrieval (IMSIR), extracts and disambiguates concepts and retrieves documents. Relevant concepts of ambiguous terms were selected using probability measures and biomedical terminologies. Concepts are also extracted using an MNBC. The UMLS (Unified Medical Language System) thesaurus was then used to filter and rank concepts. Finally, we exploited a Bayesian network to match documents and queries using a conceptual representation. Our main contribution in this paper is to combine a supervised method (MNBC) and an unsupervised method (BN) to extract concepts from documents and queries. We also propose filtering the extracted concepts in order to keep relevant ones. Experiments of IMSIR using the two corpora, the OHSUMED corpus and the Clinical Trial (CT) corpus, were interesting because their results outperformed those of the baseline: the P@50 improvement rate was +36.5% over the baseline when the CT corpus was used.
Frequency and Outcomes of Patients Presenting with Non-ST Elevation Myocardial Infarction (NSTEMI) without Standard Modifiable Risk Factors: A US Healthcare Experience
Authors: Anderson Jeffrey L. , Knight Stacey , May Heidi T. , Le Viet T. , Bair Tami L. , Knowlton Kirk U. , Muhlestein Joseph B.
Published: May 2023

Patients with ST-elevation myocardial infarction (STEMI), but without standard modifiable risk factors (SMuRF-less), are surprisingly common and appear to have a worse, or at best similar, short-term prognosis. However, relatively little attention has been paid to the prevalence and prognosis of SMuRF-less patients with non-STEMI (NSTEMI). The aim of our study was to identify the proportion and outcomes of SMuRF-less NSTEMI patients in a large US healthcare population. Patients with NSTEMI between 2001–2021 presenting to Intermountain Healthcare hospitals and catheterization laboratories were included. SMuRF-less status was defined as no clinical diagnosis of, or treatment for, hypertension, hyperlipidemia, diabetes, and smoking. Outcomes were assessed at 60 days and long-term for major adverse cardiovascular events (MACE: death, myocardial infarction, and heart failure hospitalization). Multivariable Cox proportional hazard regression was used to determine MACE hazard ratios (HR) for SMuRF-less versus patients with SMuRF. NSTEMI patients totaled 8196, of which 1458 (17.8%) were SMuRF-less. SMuRF-less patients were younger, more frequently male, had fewer comorbidities, and were slightly less likely to have revascularization. For SMuRF-less patients, 60-day MACE outcomes were lower (adj HR = 0.55, p < 0.0001), and this persisted for long-term MACE outcomes (adj HR = 0.64, p < 0.0001) and for each of its components. In this large US healthcare population, SMuRF-less NSTEMI presentation, as with STEMI presentation, was found to be common (17.8%). However, unlike STEMI reports, short- and long-term outcomes were better for SMuRF-less patients. Further studies to increase understanding of risk factors and preventive measures for NSTEMI in SMuRF-less patients are indicated.
Language Change and Morphological Processes in Contemporary Chinese: The Case of 健康码 (Health QR Code)
Authors: Xiao Yun , Ren Yi
Published: May 2023

The Chinese language has witnessed remarkable changes in the past several decades, marked by a rapid rise of new words, frequent innovation of pseudo-affixes, and a notable increase in word length. By analyzing the creation, spread, and expansion of the new word 健康码 Jiankang-ma “health QR code”, this study sheds light on how language change takes place and how nonce formation is brought into being. Following the explosion of COVID-19 in China, 健康码 Jiankang-ma “health QR code” was created and promoted by the local and central governments and subsequently generated a large XX-码 XX-ma “XX-code” word family through various morphological processes, such as abbreviation, clipping, derivation, and analogy, where -码 -ma “-code” has acquired some new meaning distinct from its original form as a bound root. Linguistically, 健康码 Jiankang-ma “health QR code” is a three-morpheme word in a 2 + 1 length pattern, which phonologically consists of a single super foot that makes the expression catchy and appealing. The highly productive AB-C internal structure makes -码 -ma “-code”, although not yet a fully grammaticalized affix, a strong pseudo-suffix that has high morphological productivity with a fixed suffix positioning. Given the high frequency of the lexical 码 ma “code” in contemporary Chinese language use, the pseudo-suffix -码 -ma “-code” may, however, not completely replace it in the long run, as principles of grammaticalization theories predict. Instead, it is likely that both the lexical 码ma “code” and the pseudo-suffix -码 -ma “-code” will coexist side by side along split pathways.
Study on the Tribological Behavior and the Interaction between Friction and Oxidation of Graphite Reinforced by Impregnated Phosphate at High Temperatures
Authors: Cheng Hao , Gao Siyang , Duan Deli , Yang Shuai , Xue Weihai , Wu Bi , Zhu Zhenguo
Published: May 2023

The stability of the graphite seal device is a key factor for the normal operation of aero engines. However, conventional graphite exhibits poor comprehensive performance due to its porous structure, which limits its application at high temperatures. Therefore, in this paper, phosphate was used to impregnated graphite pores, and the interaction between the friction, wear, and oxidation of phosphate-impregnated graphite against superalloy at high temperatures was studied through pin-on-disk friction tests. The results revealed that the coefficient of friction (COF) of matrix graphite fluctuated greatly, from 0.07 to 0.17, in the range of 100 °C to 500 °C, while the COF of impregnated graphite was stable, at around 0.13, from 100 °C to 500 °C. The wear rates of the two types of graphite were close from 20 °C to 300 °C, while the wear rate of the impregnated graphite was significantly lower than that of the matrix graphite at higher temperatures, from 400 °C and 500 °C. The reason was that the impregnated phosphate reacted with graphite at a high temperature, forming the inert site which helped to inhibit the oxidation and maintain the mechanical properties of the impregnated graphite at high temperatures. In addition, the impregnated graphite could maintain better integrity of the contact surface and reduce the inclusion of large hard metal oxides, thus effectively reducing the abrasive wear of the disk. Therefore, the wear depth of the superalloy disk samples with impregnated graphite was significantly lower than that of the matrix graphite. The results promote the application of phosphate-impregnated graphite under the high temperature conditions of aero engines.
Hypericin Ameliorates Depression-like Behaviors via Neurotrophin Signaling Pathway Mediating m6A Epitranscriptome Modification
Authors: Lei Chunguang , Li Ningning , Chen Jianhua , Wang Qingzhong
Published: May 2023

Hypericin, one of the major antidepressant constituents of St. John’s wort, was shown to exert antidepressant effects by affecting cerebral CYP enzymes, serotonin homeostasis, and neuroinflammatory signaling pathways. However, its exact mechanisms are unknown. Previous clinical studies reported that the mRNA modification N6-methyladenosine (m6A) interferes with the neurobiological mechanism in depressed patients, and it was also found that the antidepressant efficacy of tricyclic antidepressants (TCAs) is related to m6A modifications. Therefore, we hypothesize that the antidepressant effect of hypericin may relate to the m6A modification of epitranscriptomic regulation. We constructed a UCMS mouse depression model and found that hypericin ameliorated depressive-like behavior in UCMS mice. Molecular pharmacology experiments showed that hypericin treatment upregulated the expression of m6A-modifying enzymes METTL3 and WTAP in the hippocampi of UCMS mice. Next, we performed MeRIP-seq and RNA-seq to study m6A modifications and changes in mRNA expression on a genome-wide scale. The genome-wide m6A assay and MeRIP-qPCR results revealed that the m6A modifications of Akt3, Ntrk2, Braf, and Kidins220 mRNA were significantly altered in the hippocampi of UCMS mice after stress stimulation and were reversed by hypericin treatment. Transcriptome assays and qPCR results showed that the Camk4 and Arhgdig genes might be related to the antidepressant efficacy of hypericin. Further gene enrichment results showed that the differential genes were mainly involved in neurotrophic factor signaling pathways. In conclusion, our results show that hypericin upregulates m6A methyltransferase METTL3 and WTAP in the hippocampi of UCMS mice and stabilizes m6A modifications to exert antidepressant effects via the neurotrophin signaling pathway. This suggests that METTL3 and WTAP-mediated changes in m6A modifications may be a potential mechanism for the pathogenesis of depression and the efficacy of antidepressants, and that the neurotrophin signaling pathway plays a key role in this process.
Immunomodulatory, Anti-Inflammatory, and Anti-Cancer Properties of Ginseng: A Pharmacological Update
Authors: Valdés-González Jose Antonio , Sánchez Marta , Moratilla-Rivera Ignacio , Iglesias Irene , Gómez-Serranillos María Pilar
Published: May 2023

Ginseng, a medicinal plant of the genus Panax, boasts a rich historical record of usage that dates back to the Paleolithic period. This botanical is extensively acknowledged and consumed in Eastern countries for its therapeutic properties, and, in Western countries, it is becoming increasingly popular as a remedy for fatigue and asthenia. This review provides an update on current research pertaining to ginseng and its isolated compounds, namely, ginsenosides and polysaccharides. The primary focus is on three crucial pharmacological activities, namely, immunomodulation, anti-inflammatory, and anti-cancer effects. The review encompasses studies on both isolated compounds and various ginseng extracts obtained from the root, leaves, and berries.
Thickness-Dependent Evolutions of Surface Reconstruction and Band Structures in Epitaxial β–In2Se3 Thin Films
Authors: Meng Qinghao , Yu Fan , Liu Gan , Zong Junyu , Tian Qichao , Wang Kaili , Qiu Xiaodong , Wang Can , Xi Xiaoxiang , Zhang Yi
Published: May 2023

Ferroelectric materials have received great attention in the field of data storage, benefiting from their exotic transport properties. Among these materials, the two-dimensional (2D) In2Se3 has been of particular interest because of its ability to exhibit both in-plane and out-of-plane ferroelectricity. In this article, we realized the molecular beam epitaxial (MBE) growth of β–In2Se3 films on bilayer graphene (BLG) substrates with precisely controlled thickness. Combining in situ scanning tunneling microscopy (STM) and angle-resolved photoemission spectroscopy (ARPES) measurements, we found that the four-monolayer β–In2Se3 is a semiconductor with a (9 × 1) reconstructed superlattice. In contrast, the monolayer β–In2Se3/BLG heterostructure does not show any surface reconstruction due to the interfacial interaction and moiré superlattice, which instead results in a folding Dirac cone at the center of the Brillouin zone. In addition, we found that the band gap of In2Se3 film decreases after potassium doping on its surface, and the valence band maximum also shifts in momentum after surface potassium doping. The successful growth of high-quality β–In2Se3 thin films would be a new platform for studying the 2D ferroelectric heterostructures and devices. The experimental results on the surface reconstruction and band structures also provide important information on the quantum confinement and interfacial effects in the epitaxial β–In2Se3 films.
Influence of Lennard–Jones Parameters in the Temperature Dependence of Real Gases Diffusion through Nanochannels
Authors: Rodríguez García Brais , Piñeiro Manuel M. , Pérez-Rodríguez Martín
Published: May 2023

Umbrella Sampling Molecular Dynamics has been used to determine transition energies for different guest molecules through hydroquinone β-clathrate nanochannels, as well as their temperature trend. This clathrate has been shown to successfully enclathrate different types of small gases with remarkable selectivity, and thus it has been proposed as a potential gas separation and storage medium. Most of these potential guest gases can be successfully modeled as single Lennard–Jones spheres. Then, to obtain a general view of diffusion probabilities for different potential guest molecules, a comparative study for different virtual guest molecules described by different Lennard–Jones parameters has been performed. A regular temperature trend has been obtained for the transition energies for the molecular model characteristic parameter range explored. Finally, to locate the transition energy values of real gases within the space of phases explored, calculations have been repeated for molecular models of different noble gases and H2. The correlation results presented allow a wide interpolation ability for determining the transition energies of potential guest molecules stored or diffusing through the nanochannels of the studied clathrate structure.
Microencapsulation of Lead-Halide Perovskites in an Oil-in-Fluorine Emulsion for Cell Imaging
Authors: Wang Jia-Xin , Liu Chang , Huang Hao , He Rui , Geng Shengyong , Yu Xue-Feng
Published: May 2023

The superior optical properties of lead-halide perovskites (LHPs) inspired significant research in cell imaging applications; many encapsulating processes have improved perovskite stabilities with comparable biosafety. Herein, facile solvent evaporation encapsulation based on an oil-in-fluorine emulsion for aqueous-stable and extremely nontoxic LHP microcapsules is described. Perfluorooctane dispersed the emulsifier fluorocarbon surfactant to form a continuous fluorine phase, while LHPs and polymethylmethacrylate (PMMA) were dispersed in 1,2-dichloroethane, then emulsified in the fluorine phase to form an oil-in-fluorine emulsion. CsPbBr3 microcapsules with a dense PMMA shell that protect fragile CsPbBr3 from the external environment and inhibit lead ion release were obtained after solvent evaporation. The CsPbBr3 microcapsules not only retained 91% of fluorescence intensity after exposure to water for 30 d but also possess extremely low cytotoxicity for MCF-7 cells. After exposure to 2 mg/mL of CsPbBr3 microcapsules for 48 h, the cell viability remained >90%. The intracellular uptake of CsPbBr3 microcapsules indicates its potential use in cell imaging.
Feeding Difficulties in Late Preterm Infants and Their Impact on Maternal Mental Health and the Mother–Infant Relationship: A Literature Review
Authors: Vizzari Giulia , Morniroli Daniela , D’Auria Arianna , Travella Paola , Bezze Elena , Sannino Patrizio , Rampini Serena , Marchisio Paola , Plevani Laura , Mosca Fabio , Giannì Maria Lorella
Published: May 2023

Late preterm infants constitute the largest subset of premature infants and are more likely to experience feeding issues leading to delayed oral feeding independence and low breastfeeding rates. Considering the increased parental concern about their infants’ nutrition and growth, we performed a literature review to provide an update on the feeding challenges faced by late preterm infants and the impact of these issues on maternal mental health and the mother–infant relationship. Based on our findings, late preterm infants have a high prevalence of feeding difficulties which need to be addressed by targeted support interventions to promote breastfeeding success and the establishment of a harmonious dyadic interaction between the mother and her infant, all of which contribute to the prevention of altered feeding behavior later in life. There is still a need for additional research to develop a standardized and shared strategy that can be proven to be effective. Should this be accomplished, it will be possible to offer appropriate support for mothers, encourage the oral skills and maturation of late preterm infants, and improve the relationship quality within the dyad.
Acute Toxicity and Pharmacokinetic Profile of an EU-GMP-Certified Cannabis sativa L. in Rodents
Authors: Filipiuc Leontina-Elena , Ştefănescu Raluca , Solcan Carmen , Ciorpac Mitică , Szilagyi Andrei , Cojocaru Dana , Stanciu Gabriela Dumitrita , Creangă Ioana , Caratașu Cătălin-Cezar , Ababei Daniela-Carmen , Gavrila Roxana-Elena , Timofte Andrei-Daniel , Filipiuc Silviu-Iulian , Bild Veronica
Published: May 2023

The conundrum of Cannabis sativa’s applications for therapeutical purposes is set apart by the hundreds of known and commercially available strains, the social, cultural and historical context, and the legalization of its use for medical purposes in various jurisdictions around the globe. In an era where targeted therapies are continuously being developed and have become the norm, it is imperative to conduct standardized, controlled studies on strains currently cultivated under Good Manufacturing Practices (GMP) certification, a standard that guarantees the quality requirements for modern medical and therapeutic use. Thus, the aim of our study is to evaluate the acute toxicity of a 15.6% THC: <1% CBD, EU-GMP certified, Cannabis sativa L. in rodents, following the OECD acute oral toxicity guidelines, and to provide an overview of its pharmacokinetic profile. Groups of healthy female Sprague-Dawley rats were treated orally with a stepwise incremental dose, each step using three animals. The absence or presence of plant-induced mortality in rats dosed at one step determined the next step. For the EU GMP-certified Cannabis sativa L. investigated, we determined an oral LD50 value of over 5000 mg/kg in rats and a human equivalent oral dose of ≈806.45 mg/kg. Additionally, no significant clinical signs of toxicity or gross pathological findings were observed. According to our data, the toxicology, safety and pharmacokinetic profile of the tested EU-GMP-certified Cannabis sativa L. support further investigations through efficacy and chronic toxicity studies in preparation for potential future clinical applications and especially for the treatment of chronic pain.
Membranolytic Activity Profile of Nonyl 3,4-Dihydroxybenzoate: A New Anti-Biofilm Compound for the Treatment of Dermatophytosis
Authors: Costa-Orlandi Caroline B. , Bila Níura M. , Bonatti Jean Lucas C. , Vaso Carolina O. , Santos Mariana B. , Polaquini Carlos R. , Santoni Biasioli Mariana M. , Herculano Rondinelli D. , Regasini Luis O. , Fusco-Almeida Ana Marisa , Mendes-Giannini Maria José S.
Published: May 2023

The ability of dermatophytes to live in communities and resist antifungal drugs may explain treatment recurrence, especially in onychomycosis. Therefore, new molecules with reduced toxicity that target dermatophyte biofilms should be investigated. This study evaluated nonyl 3,4-dihydroxybenzoate (nonyl) susceptibility and mechanism of action on planktonic cells and biofilms of T. rubrum and T. mentagrophytes. Metabolic activities, ergosterol, and reactive oxygen species (ROS) were quantified, and the expression of genes encoding ergosterol was determined by real-time PCR. The effects on the biofilm structure were visualized using confocal electron microscopy, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). T. rubrum and T. mentagrophytes biofilms were susceptible to nonyl and resistant to fluconazole, griseofulvin (all strains), and terbinafine (two strains). The SEM results revealed that nonyl groups seriously damaged the biofilms, whereas synthetic drugs caused little or no damage and, in some cases, stimulated the development of resistance structures. Confocal microscopy showed a drastic reduction in biofilm thickness, and transmission electron microscopy results indicated that the compound promoted the derangement and formation of pores in the plasma membrane. Biochemical and molecular assays indicated that fungal membrane ergosterol is a nonyl target. These findings show that nonyl 3,4-dihydroxybenzoate is a promising antifungal compound.
DCAT: Dual Cross-Attention-Based Transformer for Change Detection
Authors: Zhou Yuan , Huo Chunlei , Zhu Jiahang , Huo Leigang , Pan Chunhong
Published: May 2023

Several transformer-based methods for change detection (CD) in remote sensing images have been proposed, with Siamese-based methods showing promising results due to their two-stream feature extraction structure. However, these methods ignore the potential of the cross-attention mechanism to improve change feature discrimination and thus, may limit the final performance. Additionally, using either high-frequency-like fast change or low-frequency-like slow change alone may not effectively represent complex bi-temporal features. Given these limitations, we have developed a new approach that utilizes the dual cross-attention-transformer (DCAT) method. This method mimics the visual change observation procedure of human beings and interacts with and merges bi-temporal features. Unlike traditional Siamese-based CD frameworks, the proposed method extracts multi-scale features and models patch-wise change relationships by connecting a series of hierarchically structured dual cross-attention blocks (DCAB). DCAB is based on a hybrid dual branch mixer that combines convolution and transformer to extract and fuse local and global features. It calculates two types of cross-attention features to effectively learn comprehensive cues with both low- and high-frequency information input from paired CD images. This helps enhance discrimination between the changed and unchanged regions during feature extraction. The feature pyramid fusion network is more lightweight than the encoder and produces powerful multi-scale change representations by aggregating features from different layers. Experiments on four CD datasets demonstrate the advantages of DCAT architecture over other state-of-the-art methods.
Multi-Transduction-Mechanism Technology, an Emerging Approach to Enhance Sensor Performance
Authors: Elnemr Youssef Ezzat , Abu-Libdeh Aya , Raj Gian Carlo Antony , Birjis Yumna , Nazemi Haleh , Munirathinam Pavithra , Emadi Arezoo
Published: May 2023

Conventional sensor systems employ single-transduction technology where they respond to an input stimulus and transduce the measured parameter into a readable output signal. As such, the technology can only provide limited corresponding data of the detected parameters due to relying on a single transformed output signal for information acquisition. This limitation commonly results in the need for utilizing sensor array technology to detect targeted parameters in complex environments. Multi-transduction-mechanism technology, on the other hand, may combine more than one transduction mechanism into a single structure. By employing this technology, sensors can be designed to simultaneously distinguish between different input signals from complex environments for greater degrees of freedom. This allows a multi-parameter response, which results in an increased range of detection and improved signal-to-noise ratio. In addition, utilizing a multi-transduction-mechanism approach can achieve miniaturization by reducing the number of required sensors in an array, providing further miniaturization and enhanced performance. This paper introduces the concept of multi-transduction-mechanism technology by exploring different candidate combinations of fundamental transduction mechanisms such as piezoresistive, piezoelectric, triboelectric, capacitive, and inductive mechanisms.
Multi-Criteria Assessment of Taxi Transport Services for Public Procurement: Case Study for Bacau City
Authors: Bibire Luminita , Chitimus Alexandra-Dana , Ghenadi Adrian-Stelian
Published: May 2023

LCA methodology is often used in public procurement decision making. The European Commission introduced Life Cycle Costing (LCC) in 2014 to support this methodology. LCCs take into account costs incurred during a service, work or product’s lifetime. Application management techniques of LCC offer a better awareness of the factors that influence the resources and costs in the case of procurements. The identification of the factors that influence the costs is the main key of the LCC tool. In such a way, the life cycle management is focused on efficient purchasing. The awareness levels of the LCC criteria influence the cost and will also highlight other aspects of existing products that could benefit from the involvement of life cycle management. Taxi transport services (as an alternative to public transportation) are a sector of the economy with a good income when acquisitions are properly carried out. When the acquisitions are analyzed, governmental and local regularizations should be taken into account. Today, cities, as well as small towns, look forward to improving the quality of life of the citizens and reducing pollution. The acquisitions of buses/cars for public use must be carried out with respect to the required performance of the cars. On the one hand, the municipality should be in line with the European Commission’s policy; on the other hand, it should be in line with the state’s public procurement requirements. An acquisition must also be reasonable in terms of price, lifetime, environmental impact, circular economy and meeting citizens’ needs. The goal of this paper was to analyze the acquisition of cars for taxi services from the perspective of public procurements. The study was performed with the help of the Taxi LAL company from Bacau County. The LCC techniques were applied to identify the most “acceptable” as well as the most “profitable” choices for taxi services. For a better understanding of the problem, within the present paper the mechanism of cost assessment for a product modernization was exemplified.