bluuebunny/crossref_metadata_2025 huggingface dataset:
Anaerobic Digestion and Alternative Manure Management Technologies for Methane Emissions Mitigation on Californian Dairies
Authors: El Mashad Hamed M. , Barzee Tyler J. , Franco Roberta Brancher , Zhang Ruihong , Kaffka Stephen , Mitloehner Frank
Published: January 2023

California is the leading dairy state in the United States. The total sale of milk and its products represents about $6.3 billion annually out of the $50 billion generated from all agricultural production in the state. However, methane emissions from dairy manure and enteric fermentation represented nearly half of all annual methane emissions in California, with dairy manure accounting for 25%, and enteric fermentation for 20%. Methane emissions originating from manure are produced primarily from anaerobic settling basins and lagoons, which are the most common manure storage systems in the state. To achieve sustainability on dairy farms and to comply with state regulations for air and climate pollutants, dairy farms have implemented technologies such as anaerobic digestion and alternative manure management technologies. In addition, governmental incentive programs have been deployed to partially fund these technologies for eligible dairies in the state. The present article reviews the design and operations, effectiveness, and economics of the most common technologies employed in Californian dairies in reducing methane emissions. The technologies studied include anaerobic digesters, mechanical separators, compost-bedded pack barns, manure vacuuming followed by drying, and weeping walls. The current status and estimated effectiveness of government incentive programs are reviewed and recommendations for improvements presented. Finally, future trends and research needs for mitigating the emissions in Californian dairies are identified.
An Analytical Solution to the One-Dimensional Unsteady Temperature Field near the Newtonian Cooling Boundary
Authors: Ren Honglei , Tao Yuezan , Wei Ting , Kang Bo , Li Yucheng , Lin Fei
Published: January 2023

One-dimensional heat-conduction models in a semi-infinite domain, although forced convection obeys Newton’s law of cooling, are challenging to solve using standard integral transformation methods when the boundary condition φ(t) is an exponential decay function. In this study, a general theoretical solution was established using Fourier transform, but φ(t) was not directly present in the transformation processes, and φ(t) was substituted into the general theoretical solution to obtain the corresponding analytical solution. Additionally, the specific solutions and corresponding mathematical meanings were discussed. Moreover, numerical verification and sensitivity analysis were applied to the proposed model. The results showed that T(x,t) was directly proportional to the thermal diffusivity (a) and was inversely proportional to calculation distance (x) and the coefficient of cooling ratio (λ). The analytical solution was more sensitive to the thermal diffusivity than other factors, and the highest relative error between numerical and analytical solutions was roughly 4% under the condition of 2a and λ. Furthermore, T(x,t) grew nonlinearly as the material’s thermal diffusivity or cooling ratio coefficient changed. Finally, the analytical solution was applied for parameter calculation and verification in a case study, providing the reference basis for numerical calculation under specific complex boundaries, especially for the study of related problems in the fields of fluid dynamics and peridynamics with the heat-conduction equation.
Identifying Immune-Specific Subtypes of Adrenocortical Carcinoma Based on Immunogenomic Profiling
Authors: Lu Qiqi , Nie Rongfang , Luo Jiangti , Wang Xiaosheng , You Linjun
Published: January 2023

Background: The tumor immune microenvironment (TIME) of adrenocortical carcinoma (ACC) is heterogeneous. However, a classification of ACC based on the TIME remains unexplored. Methods: We hierarchically clustered ACC based on the enrichment levels of twenty-three immune signatures to identify its immune-specific subtypes. Furthermore, we comprehensively compared the clinical and molecular profiles between the subtypes. Results: We identified two immune-specific subtypes of ACC: Immunity-H and Immunity-L, which had high and low immune signature scores, respectively. We demonstrated that this subtyping method was stable and reproducible by analyzing five different ACC cohorts. Compared with Immunity-H, Immunity-L had lower levels of immune cell infiltration, worse overall and disease-free survival prognosis, and higher tumor stemness, genomic instability, proliferation potential, and intratumor heterogeneity. Furthermore, the ACC driver gene CTNNB1 was more frequently mutated in Immunity-L than in Immunity-H. Several proteins, such as mTOR, ERCC1, Akt, ACC1, Cyclin_E1, β-catenin, FASN, and GAPDH, were more highly expressed in Immunity-L than in Immunity-H. In contrast, p53, Syk, Lck, PREX1, and MAPK were more highly expressed in Immunity-H. Pathway and gene ontology analysis showed that the immune, stromal, and apoptosis pathways were highly enriched in Immunity-H, while the cell cycle, steroid biosynthesis, and DNA damage repair pathways were highly enriched in Immunity-L. Conclusions: ACC can be classified into two stable immune-related subtypes, which have significantly different antitumor responses, molecular characteristics, and clinical outcomes. This subtyping may provide clinical implications for prognostic and immunotherapeutic stratification of ACC.
Identification and Characterization of Hdh-FMRF2 Gene in Pacific Abalone and Its Possible Role in Reproduction and Larva Development
Authors: Sukhan Zahid Parvez , Cho Yusin , Hossen Shaharior , Lee Won Kyo , Kho Kang Hee
Published: January 2023

FMRFamide-related peptides are neuropeptides involved in a wide range of biological processes, including reproduction and larval development. To characterize the involvement of FMRFamide in the reproduction and larval development of Pacific abalone Haliotis discus hannai, an FMRFamide cDNA (Hdh-FMRF2) was cloned from the cerebral ganglion (CG). Fluorescence in situ hybridization and qRT-PCR were performed for functional characterization. The Hdh-FMRF2 cDNA encoded 204 deduced amino acids that contained a putative signal peptide and four FaRP domains. The major population of Hdh-FMRF2 neuronal cell bodies was localized in the cortex of CG. Hdh-FMRF2 mRNA expression was significantly upregulated in CG during the mature stage of gonadal development and effective accumulative temperature (EAT) exposed abalone in both sexes. In the induced spawning event, Hdh-FMRF2 expression was significantly upregulated during spawning in males. However, no upregulation was observed in females, suggesting Hdh-FMRF2 might inhibit gamete release in female abalone. These results revealed Hdh-FMRF2 as a reproduction related peptide. Furthermore, mRNA expression in larval development suggested that this peptide was also involved in larval development during development of Pacific abalone. Collectively, this study provides evidence of possible involvement of an FMRFamide neuropeptide in the reproduction and larval development of Pacific abalone.
Recent Trends in Metal Nanoparticles Decorated 2D Materials for Electrochemical Biomarker Detection
Authors: Koyappayil Aneesh , Yagati Ajay Kumar , Lee Min-Ho
Published: January 2023

Technological advancements in the healthcare sector have pushed for improved sensors and devices for disease diagnosis and treatment. Recently, with the discovery of numerous biomarkers for various specific physiological conditions, early disease screening has become a possibility. Biomarkers are the body’s early warning systems, which are indicators of a biological state that provides a standardized and precise way of evaluating the progression of disease or infection. Owing to the extremely low concentrations of various biomarkers in bodily fluids, signal amplification strategies have become crucial for the detection of biomarkers. Metal nanoparticles are commonly applied on 2D platforms to anchor antibodies and enhance the signals for electrochemical biomarker detection. In this context, this review will discuss the recent trends and advances in metal nanoparticle decorated 2D materials for electrochemical biomarker detection. The prospects, advantages, and limitations of this strategy also will be discussed in the concluding section of this review.
The Buffering Effect of Awe on Negative Emotions in Self-Threatening Situations
Authors: Sun Zhaoyang , Hou Yubo , Song Lili , Wang Kun , Yuan Mengchan
Published: January 2023

Negative emotions arising from self-threat are ubiquitous and harmful. We propose that the experience of awe awakens the small-self, which in turn alleviates these negative emotions. We examine our theoretical hypotheses in four studies employing various self-threatening situations, using distinct awe manipulations and involving participants from different countries. The participants experiencing awe reported lower levels of negative emotions arising from self-threat compared with those in the neutral (Study 1) and happiness conditions (Study 2). Moreover, we verified that the small-self mediates the alleviating effect of awe on negative emotions through measuring (Study 3) and manipulating the small-self (Study 4). Beyond a set of practical implications for promoting mental health and well-being, our research also provides novel insights into awe, self-appraisal, and self-threat.
High Indoor Rn Concentration Mitigation in a Heritage Building: Case Study Analysis of the Applied Constructive Measures
Authors: Nunes Leonel J. R. , Curado António
Published: January 2023

Indoor radon (Rn) concentration is pointed out by the World Health Organization (WHO) as the second leading cause of lung cancer. Adopting mitigation measures based on ventilation procedures is an effective solution for most cases. However, the occurrence of abnormal concentrations of indoor Rn in heritage buildings, where most interventions are restricted, may lead to alternative remediation techniques. In these cases, constructive mitigation measures, such as the use of barrier membranes on the floor or specific coating mortars on the walls, can be adequate solutions. In the current investigation, two constructive measures were applied and analyzed sequentially. The preliminary long-term monitoring campaign registered extremely high indoor Rn concentration measurements. The application of a barrier membrane covering the floor of the test compartment allowed a 90% reduction in the average Rn concentration, but it nevertheless remained substantially above the recommended value of 300 Bq·m−3. Subsequently, a coating mortar was applied on the walls. The combined measures contributed to a total reduction of 94% in the average indoor Rn concentration, which remains slightly above the recommended exposure limit. Despite the verified reduction and the apparent effectiveness of the measures, it is still necessary to carry out more monitoring campaigns to test their general applicability.
Vector-Valued Intensity Measures Based on Spectral Shape to Predict Seismic Fragility Surfaces in Reinforced Concrete Buildings
Authors: Zavala Noel , Bojórquez Edén , Barraza Manuel , Bojórquez Juan , Villela Almendra , Campos José , Torres José , Sánchez Ricardo , Carvajal Joel
Published: January 2023

Although some studies have been conducted to compute fragility surfaces of buildings using vector-valued seismic intensity measures (IMs), in all the cases, the first component of the vector usually is the spectral acceleration at first mode of vibration of the structure Sa(T1). In this study, fragility surfaces of three reinforced concrete buildings (RCB) subjected to narrow-band ground motions obtained from soft soil of Mexico City are computed considering vector-valued IMs based not only on Sa(T1), but also the velocity V(T1), pseudo-velocity Sv(T1), and normalized input energy by the mass EI/m(T1) as the first component. As second component of the vector-valued IMs, the Peak Ground Acceleration (PGA), Peak Ground Velocity (PGV), effective duration (tD), earthquake damage potential (ID) and four Np spectral shape-based parameters obtained through spectral acceleration (NpSa), velocity (NpV), pseudo-velocity (NpSv), and input energy (NpEI) have been analyzed. In order to obtain fragility surfaces, Multinomial Logistic Regression (MLR) was applied. It is observed that those vector-valued IMs based on the spectral shape proxies were more efficient to predict the probability of failure of RCB. For this reason, it is important to consider spectral shape vector-valued IMs in order to reduce uncertainty in the structural response of buildings under earthquakes. Thus, the use of two parameters instead of a single intensity measure improves the efficiency. Moreover, the fragility surfaces can be used for the seismic risk evaluation of buildings.
Therapeutic Drug Monitoring of Tyrosine Kinase Inhibitors in the Treatment of Advanced Renal Cancer
Authors: Puisset Florent , Mseddi Mourad , Mourey Loïc , Pouessel Damien , Blanchet Benoit , Chatelut Etienne , Chevreau Christine
Published: January 2023

Seven tyrosine kinase inhibitor compounds with anti-angiogenic properties remain key drugs to treat advanced renal cell carcinoma. There is a strong rationale to develop therapeutic drug monitoring for these drugs. General considerations of such monitoring of the several groups of anticancer drugs are given, with a focus on oral therapy. Pharmacokinetics and the factors of inter- and intraindividual variabilities of these tyrosine kinase inhibitors are described together with an exhaustive presentation of their pharmacokinetic/pharmacodynamic relationships. The latter was observed in studies where every patient was treated with the same dose, and the results of several prospective studies based on dose individualization support the practice of increasing individual dosage in case of low observed plasma drug concentrations. Finally, the benefits and limits of therapeutic drug monitoring as a routine practice are discussed.
Immunotherapy for Triple-Negative Breast Cancer: Combination Strategies to Improve Outcome
Authors: Li Liying , Zhang Fan , Liu Zhenyu , Fan Zhimin
Published: January 2023

Due to the absence of hormone receptor (both estrogen receptors and progesterone receptors) along with human epidermal growth factor receptor 2 (HER-2) amplification, the treatment of triple-negative breast cancer (TNBC) cannot benefit from endocrine or anti-HER-2 therapy. For a long time, chemotherapy was the only systemic treatment for TNBC. Due to the lack of effective treatment options, the prognosis for TNBC is extremely poor. The successful application of immune checkpoint inhibitors (ICIs) launched the era of immunotherapy in TNBC. However, the current findings show modest efficacy of programmed cell death- (ligand) 1 (PD-(L)1) inhibitors monotherapy and only a small proportion of patients can benefit from this approach. Based on the basic principles of immunotherapy and the characteristics of the tumor immune microenvironment (TIME) in TNBC, immune combination therapy is expected to further enhance the efficacy and expand the beneficiary population of patients. Given the diversity of drugs that can be combined, it is important to select effective biomarkers to identify the target population. Moreover, the side effects associated with the combination of multiple drugs should also be considered.
A Subset of PD-1-Expressing CD56bright NK Cells Identifies Patients with Good Response to Immune Checkpoint Inhibitors in Lung Cancer
Authors: Gascón-Ruiz Marta , Ramírez-Labrada Ariel , Lastra Rodrigo , Martínez-Lostao Luis , Paño-Pardo J. Ramón , Sesma Andrea , Zapata-García María , Moratiel Alba , Quílez Elisa , Torres-Ramón Irene , Yubero Alfonso , Domingo María Pilar , Esteban Patricia , Gálvez Eva M. , Pardo Julián , Isla Dolores
Published: January 2023

(1) Despite the effectiveness of immune checkpoint inhibitors (ICIs) in lung cancer, there is a lack of knowledge about predictive biomarkers. The objective of our study is to analyze different subsets of T-lymphocytes and natural killer (NK) cells as predictive biomarkers in a cohort of patients with nonsmall cell lung cancer (NSCLC) treated with ICI. (2) This is an observational, prospective study with 55 NSCLC patients treated with ICI. A total of 43 T and NK cell subsets are analyzed in peripheral blood, including the main markers of exhaustion, differentiation, memory, activation, and inhibition. (3) Regarding the descriptive data, Granzyme B+CD4+ Treg lymphocytes stand out (median 17.4%), and within the NK populations, most patients presented cytotoxic NK cells (CD56+CD3−CD16+GranzymeB+; median 94.8%), and about half of them have highly differentiated adaptive-like NK cells (CD56+CD3−CD16+CD57+ (mean 59.8%). A statistically significant difference was observed between the expression of PD1 within the CD56bright NK cell subpopulation (CD56+CD3−CD16−PD-1+) (p = 0.047) and a better OS. (4) Circulating immune cell subpopulations are promising prognostic biomarkers for ICI. Pending on validation with a larger sample, here we provide an analysis of the major circulating T and NK cell subsets involved in cancer immunity, with promising results despite a small sample size.
Ocular Complications of Radiotherapy in Uveal Melanoma
Authors: Zemba Mihail , Dumitrescu Otilia-Maria , Gheorghe Alina Gabriela , Radu Madalina , Ionescu Mihai Alexandru , Vatafu Andrei , Dinu Valentin
Published: January 2023

Uveal melanoma is the most common primary malignant intraocular tumor in adults. Radiation therapy has replaced enucleation and is now the preferred treatment in most cases. Nonetheless, around 70% of patients develop radiation-related complications, some of which are vision-threatening. The objective of this review is to present the most important complications associated with radiotherapy in the treatment of uveal melanoma and their pathogenesis, incidence, risk factors, and available preventive and therapeutic measures. The most common complications are cataracts, with a reported incidence ranging from 4% to 69%, and radiation retinopathy, reported in 5–68% of cases. Radiation-related complications are responsible for approximately half of secondary enucleations, the leading cause being neovascular glaucoma. A poor visual outcome is mainly associated with the presence of radiation retinopathy and radiation optic neuropathy. Therapeutic options are available for the majority of complications with the notable exception of optic neuropathy. However, many studies report a final visual acuity of less than 20/200 in more than 60% of treated eyes. Reducing complication rates can be achieved by lowering the dose of radiation, with the use of eccentric, customized plaques and careful planning of the irradiation delivery in order to protect structures vital to vision and by associating radiation therapy with other methods with the aim of reducing tumor volume.
Therapeutic Targeting of Cancer-Associated Fibroblasts in the Non-Small Cell Lung Cancer Tumor Microenvironment
Authors: Shintani Yasushi , Kimura Toru , Funaki Soichiro , Ose Naoko , Kanou Takashi , Fukui Eriko
Published: January 2023

Lung cancer is the most frequently diagnosed cancer and the leading cause of cancer death worldwide. The most common lung cancer is non-small cell lung cancer (NSCLC), with an overall 5-year survival rate of around 20% because NSCLC is a metastatic disease. A better understanding of the mechanism underlying lung cancer metastasis is therefore urgently needed. The tumor microenvironment involves different types of stromal cells and functions as key components in the progression of NSCLC. Through epithelial–mesenchymal transition (EMT), in which epithelial cells lose their polarity and acquire mesenchymal potential, cancer cells acquire metastatic abilities, as well as cancer stem-cell-like potential. We previously reported that cancer-associated fibroblasts (CAFs) interact with lung cancer cells to allow for the acquisition of malignancy and treatment resistance by paracrine loops via EMT signals in the tumor microenvironment. Furthermore, CAFs regulate the cytotoxic activity of immune cells via various cytokines and chemokines, creating a microenvironment of immune tolerance. Regulation of CAFs can therefore affect immune responses. Recent research has shown several roles of CAFs in NSCLC tumorigenesis, owing to their heterogeneity, so molecular markers of CAFs should be elucidated to better classify tumor-promoting subtypes and facilitate the establishment of CAF-specific targeted therapies. CAF-targeted cancer treatments may suppress EMT and regulate the niche of cancer stem cells and the immunosuppressive network and thus may prove useful for NSCLC treatment through multiple mechanisms.
FOXP3 Isoforms Expression in Cervical Cancer: Evidence about the Cancer-Related Properties of FOXP3Δ2Δ7 in Keratinocytes
Authors: Garcia-Becerra Natalia , Aguila-Estrada Marco Ulises , Palafox-Mariscal Luis Arturo , Hernandez-Flores Georgina , Aguilar-Lemarroy Adriana , Jave-Suarez Luis Felipe
Published: January 2023

Cervical cancer (CC) is the fourth most common type of cancer among women; the main predisposing factor is persistent infection by high-risk human papillomavirus (hr-HPV), mainly the 16 or 18 genotypes. Both hr-HPVs are known to manipulate the cellular machinery and the immune system to favor cell transformation. FOXP3, a critical transcription factor involved in the biology of regulatory T cells, has been detected as highly expressed in the tumor cells of CC patients. However, its biological role in CC, particularly in the keratinocytes, remained unclarified. Therefore, this work aimed to uncover the effect of FOXP3 on the biology of the tumoral cells. First, public databases were analyzed to identify the FOXP3 expression levels and the transcribed isoforms in CC and normal tissue samples. The study’s findings demonstrated an increased expression of FOXP3 in HPV16+ CC samples. Additionally, the FOXP3Δ2 variant was detected as the most frequent splicing isoform in tumoral cells, with a high differential expression level in metastatic samples. However, the analysis of FOXP3 expression in different CC cell lines, HPV+ and HPV-, suggests no relationship between the presence of HPV and FOXP3 expression. Since the variant FOXP3Δ2Δ7 was found highly expressed in the HPV16+ SiHa cell line, a model with constitutive expression of FOXP3Δ2Δ7 was established to evaluate its role in proliferation, migration, and cell division. Finally, RNAseq was performed to identify differentially expressed genes and enriched pathways modulated by FOXP3Δ2Δ7. The exogenous expression of FOXP3Δ2Δ7 promotes cell division, proliferation, and migration. The transcriptomic analyses highlight the upregulation of multiple genes with protumor activities. Moreover, immunological and oncogenic pathways were detected as highly enriched. These data support the hypothesis that FOXP3Δ2Δ7 in epithelial cells induces cancer-related hallmarks and provides information about the molecular events triggered by this isoform, which could be important for developing CC.
Risk Assessment and Pancreatic Cancer: Diagnostic Management and Artificial Intelligence
Authors: Granata Vincenza , Fusco Roberta , Setola Sergio Venanzio , Galdiero Roberta , Maggialetti Nicola , Silvestro Lucrezia , De Bellis Mario , Di Girolamo Elena , Grazzini Giulia , Chiti Giuditta , Brunese Maria Chiara , Belli Andrea , Patrone Renato , Palaia Raffaele , Avallone Antonio , Petrillo Antonella , Izzo Francesco
Published: January 2023

Pancreatic cancer (PC) is one of the deadliest cancers, and it is responsible for a number of deaths almost equal to its incidence. The high mortality rate is correlated with several explanations; the main one is the late disease stage at which the majority of patients are diagnosed. Since surgical resection has been recognised as the only curative treatment, a PC diagnosis at the initial stage is believed the main tool to improve survival. Therefore, patient stratification according to familial and genetic risk and the creation of screening protocol by using minimally invasive diagnostic tools would be appropriate. Pancreatic cystic neoplasms (PCNs) are subsets of lesions which deserve special management to avoid overtreatment. The current PC screening programs are based on the annual employment of magnetic resonance imaging with cholangiopancreatography sequences (MR/MRCP) and/or endoscopic ultrasonography (EUS). For patients unfit for MRI, computed tomography (CT) could be proposed, although CT results in lower detection rates, compared to MRI, for small lesions. The actual major limit is the incapacity to detect and characterize the pancreatic intraepithelial neoplasia (PanIN) by EUS and MR/MRCP. The possibility of utilizing artificial intelligence models to evaluate higher-risk patients could favour the diagnosis of these entities, although more data are needed to support the real utility of these applications in the field of screening. For these motives, it would be appropriate to realize screening programs in research settings.
Treatment Outcomes and Prognostic Factors of Gemcitabine Plus Nab-Paclitaxel as Second-Line Chemotherapy after Modified FOLFIRINOX in Unresectable Pancreatic Cancer
Authors: Mie Takafumi , Sasaki Takashi , Takeda Tsuyoshi , Okamoto Takeshi , Hamada Tsuyoshi , Ishitsuka Takahiro , Yamada Manabu , Nakagawa Hiroki , Furukawa Takaaki , Kasuga Akiyoshi , Matsuyama Masato , Ozaka Masato , Sasahira Naoki
Published: January 2023

Outcomes and prognostic factors of second-line gemcitabine plus nab-paclitaxel (GnP) after modified FOLFIRINOX (mFFX) for unresectable pancreatic cancer were unclear. We retrospectively analyzed consecutive patients with unresectable pancreatic cancer treated with GnP after first-line mFFX treatment between March 2015 and March 2022 at our hospital. A total of 103 patients were included. Median overall survival (OS) from the start of first-line and second-line treatments was 14.9 months and 7.2 months, respectively. Median progression-free survival (PFS) was 3.6 months. Performance status, modified Glasgow prognostic score, and neutrophil-to-lymphocyte ratio were independently associated with OS. Our prognostic model using these parameters classifies patients into good (n = 70) and poor (n = 33) prognosis groups. Median OS and PFS were longer in the good prognosis group than in the poor prognosis group (OS: 9.3 vs. 3.8 months, p < 0.01; PFS: 4.1 vs. 2.3 months, p < 0.01). Grade 3/4 adverse events were observed in 70.9% of patients, with neutropenia being the most frequent. While GnP as second-line treatment was well-tolerated, efficacy of second-line gemcitabine plus nab-paclitaxel was notably limited, particularly in the poor prognosis group.
Cissus quadrangularis (Hadjod) Inhibits RANKL-Induced Osteoclastogenesis and Augments Bone Health in an Estrogen-Deficient Preclinical Model of Osteoporosis Via Modulating the Host Osteoimmune System
Authors: Azam Zaffar , Sapra Leena , Baghel Kalpana , Sinha Niharika , Gupta Rajesh K. , Soni Vandana , Saini Chaman , Mishra Pradyumna K. , Srivastava Rupesh K.
Published: January 2023

Osteoporosis is a systemic skeletal disease characterised by low bone mineral density (BMD), degeneration of bone micro-architecture, and impaired bone strength. Cissus quadrangularis (CQ), popularly known as Hadjod (bone setter) in Hindi, is a traditional medicinal herb exhibiting osteoprotective potential in various bone diseases, especially osteoporosis and fractures. However, the cellular mechanisms underpinning its direct effect on bone health through altering the host immune system have never been elucidated. In the present study, we interrogated the osteoprotective and immunoporotic (the osteoprotective potential of CQ via modulating the host immune system) potential of CQ in preventing inflammatory bone loss under oestrogen-deficient conditions. The current study outlines the CQ’s osteoprotective potential under both ex vivo and in vivo (ovariectomized) conditions. Our ex vivo data demonstrated that, in a dose-dependent manner CQ, suppresses the RANKL-induced osteoclastogenesis (p < 0.001) as well as inhibiting the osteoclast functional activity (p < 0.001) in mouse bone marrow cells (BMCs). Our in vivo µ-CT and flow cytometry data further showed that CQ administration improves bone health and preserves bone micro-architecture by markedly raising the proportion of anti-osteoclastogenic immune cells, such as Th1 (p < 0.05), Th2 (p < 0.05), Tregs (p < 0.05), and Bregs (p < 0.01), while concurrently lowering the osteoclastogenic Th17 cells in bone marrow, mesenteric lymph nodes, Peyer’s patches, and spleen in comparison to the control group. Serum cytokine analysis further supported the osteoprotective and immunoporotic potential of CQ, showing a significant increase in the levels of anti-osteoclastogenic cytokines (p < 0.05) (IFN-γ, IL-4, and IL-10) and a concurrent decrease in the levels of osteoclastogenic cytokines (p < 0.05) (TNF-α, IL-6, and IL-17). In conclusion, our data for the first time delineates the novel cellular and immunological mechanism of the osteoprotective potential of CQ under postmenopausal osteoporotic conditions.
Heat Shock Protein 27 Is Involved in the Bioactive Glass Induced Osteogenic Response of Human Mesenchymal Stem Cells
Authors: Hyväri Laura , Vanhatupa Sari , Ojansivu Miina , Kelloniemi Minna , Pakarinen Toni-Karri , Hupa Leena , Miettinen Susanna
Published: January 2023

Bioactive glass (BaG) materials are increasingly used in clinics, but their regulatory mechanisms on osteogenic differentiation remain understudied. In this study, we elucidated the currently unknown role of the p38 MAPK downstream target heat shock protein 27 (HSP27), in the osteogenic commitment of human mesenchymal stem cells (hMSCs), derived from adipose tissue (hASCs) and bone marrow (hBMSCs). Osteogenesis was induced with ionic extract of an experimental BaG in osteogenic medium (OM). Our results showed that BaG OM induced fast osteogenesis of hASCs and hBMSCs, demonstrated by enhanced alkaline phosphatase (ALP) activity, production of extracellular matrix protein collagen type I, and matrix mineralization. BaG OM stimulated early and transient activation of p38/HSP27 signaling by phosphorylation in hMSCs. Inhibition of HSP27 phosphorylation with SB202190 reduced the ALP activity, mineralization, and collagen type I production induced by BaG OM. Furthermore, the reduced pHSP27 protein by SB202190 corresponded to a reduced F-actin intensity of hMSCs. The phosphorylation of HSP27 allowed its co-localization with the cytoskeleton. In terminally differentiated cells, however, pHSP27 was found diffusely in the cytoplasm. This study provides the first evidence that HSP27 is involved in hMSC osteogenesis induced with the ionic dissolution products of BaG. Our results indicate that HSP27 phosphorylation plays a role in the osteogenic commitment of hMSCs, possibly through the interaction with the cytoskeleton.
Establishing Hedgehog Gradients during Neural Development
Authors: Douceau Sara , Deutsch Guerrero Tanya , Ferent Julien
Published: January 2023

A morphogen is a signaling molecule that induces specific cellular responses depending on its local concentration. The concept of morphogenic gradients has been a central paradigm of developmental biology for decades. Sonic Hedgehog (Shh) is one of the most important morphogens that displays pleiotropic functions during embryonic development, ranging from neuronal patterning to axon guidance. It is commonly accepted that Shh is distributed in a gradient in several tissues from different origins during development; however, how these gradients are formed and maintained at the cellular and molecular levels is still the center of a great deal of research. In this review, we first explored all of the different sources of Shh during the development of the nervous system. Then, we detailed how these sources can distribute Shh in the surrounding tissues via a variety of mechanisms. Finally, we addressed how disrupting Shh distribution and gradients can induce severe neurodevelopmental disorders and cancers. Although the concept of gradient has been central in the field of neurodevelopment since the fifties, we also describe how contemporary leading-edge techniques, such as organoids, can revisit this classical model.
Early Regional Patterning in the Human Prefrontal Cortex Revealed by Laminar Dynamics of Deep Projection Neuron Markers
Authors: Kopić Janja , Junaković Alisa , Salamon Iva , Rasin Mladen-Roko , Kostović Ivica , Krsnik Željka
Published: January 2023

Early regional patterning and laminar position of cortical projection neurons is determined by activation and deactivation of transcriptional factors (TFs) and RNA binding proteins (RBPs) that regulate spatiotemporal framework of neurogenetic processes (proliferation, migration, aggregation, postmigratory differentiation, molecular identity acquisition, axonal growth, dendritic development, and synaptogenesis) within transient cellular compartments. Deep-layer projection neurons (DPN), subplate (SPN), and Cajal–Retzius neurons (CRN) are early-born cells involved in the establishment of basic laminar and regional cortical architecture; nonetheless, laminar dynamics of their molecular transcriptional markers remain underexplored. Here we aimed to analyze laminar dynamics of DPN markers, i.e., transcription factors TBR1, CTIP2, TLE4, SOX5, and RBP CELF1 on histological serial sections of the human frontal cortex between 7.5–15 postconceptional weeks (PCW) in reference to transient proliferative, migratory, and postmigratory compartments. The subtle signs of regional patterning were seen during the late preplate phase in the pattern of sublaminar organization of TBR1+/Reelin+ CRN and TBR1+ pioneering SPN. During the cortical plate (CP)-formation phase, TBR1+ neurons became radially aligned, forming continuity from a well-developed subventricular zone to CP showing clear lateral to medial regional gradients. The most prominent regional patterning was seen during the subplate formation phase (around 13 PCW) when a unique feature of the orbitobasal frontal cortex displays a “double plate” pattern. In other portions of the frontal cortex (lateral, dorsal, medial) deep portion of CP becomes loose and composed of TBR1+, CTIP2+, TLE4+, and CELF1+ neurons of layer six and later-born SPN, which later become constituents of the expanded SP (around 15 PCW). Overall, TFs and RBPs mark characteristic regional laminar dynamics of DPN, SPN, and CRN subpopulations during remarkably early fetal phases of the highly ordered association cortex development.
OPA1 Dominant Optic Atrophy: Diagnostic Approach in the Pediatric Population
Authors: Arruti Natalia , Rodríguez-Solana Patricia , Nieves-Moreno María , Guerrero-Carretero Marta , del Pozo Ángela , Montaño Victoria E. F. , Santos-Simarro Fernando , Rikeros-Orozco Emi , Delgado-Mora Luna , Vallespín Elena , Noval Susana
Published: January 2023

A clinical and genetic study was conducted with pediatric patients and their relatives with optic atrophy 1 (OPA1) mutations to establish whether there is a genotype–phenotype correlation among the variants detected within and between families. Eleven children with a confirmed OPA1 mutation were identified during the study period. The main initial complaint was reduced visual acuity (VA), present in eight patients of the cohort. Eight of eleven patients had a positive family history of optic atrophy. The mean visual acuity at the start of the study was 0.40 and 0.44 LogMAR in the right and left eye, respectively. At the end of the study, the mean visual acuity was unchanged. Optical coherence tomography during the first visit showed a mean retinal nerve fiber layer thickness of 81.6 microns and 80.5 microns in the right and left eye, respectively; a mean ganglion cell layer of 52.5 and 52.4 microns, respectively, and a mean central macular thickness of 229.5 and 233.5 microns, respectively. The most common visual field defect was a centrocecal scotoma, and nine out of eleven patients showed bilateral temporal disc pallor at baseline. Sequencing of OPA1 showed seven different mutations in the eleven patients, one of which, NM_130837.3: c.1406_1407del (p.Thr469LysfsTer16), has not been previously reported. Early diagnosis of dominant optic atrophy is crucial, both for avoiding unnecessary consultations and/or treatments and for appropriate genetic counseling.
Protective Effect of Vitamin D against Hepatic Molecular Apoptosis Caused by a High-Fat Diet in Rats
Authors: Alshaibi Huda F. , Bakhashab Sherin , Almuhammadi Asma , Althobaiti Yusuf S. , Baghdadi Mohammed A. , Alsolami Khadeejah
Published: January 2023

The protective effects of vitamin D (VitD) in different diseases were studied. The liver is of great interest, especially with the presence of VitD receptors. A high-fat diet (HFD) is associated with many diseases, including liver injury. Consumption of saturated fatty acids triggers hepatic apoptosis and is associated with increased inflammation. We aimed in this study to investigate the protective effects of VitD on hepatic molecular apoptotic changes in response to an HFD in rats. Forty male Wistar albino rats were used and divided into four groups: control, HFD, control + VitD, and VitD-supplemented HFD (HFD + VitD) groups. After six months, the rats were sacrificed, and the livers were removed. RNA was extracted from liver tissues and used for the quantitative real-time RT-PCR of different genes: B-cell lymphoma/leukemia-2 (BCL2), BCL-2-associated X protein (Bax), Fas cell surface death receptor (FAS), FAS ligand (FASL), and tumor necrosis factor α (TNF-α). The results showed that an HFD increased the expression of the pro-apoptotic genes Bax, FAS, and FASL, and reduced the expression of the anti-apoptotic gene BCL2. Interestingly, a VitD-supplemented HFD significantly increased the BCL2 expression and decreased the expression of all pro-apoptotic genes and TNFα. In conclusion, VitD has a protective role against hepatic molecular apoptotic changes in response to an HFD.
In Vitro Investigation of Corrosion Control of Magnesium with Degradable Polycaprolactone Coatings for Cardiovascular Grafts
Authors: Knigge Sara , Mueller Marc , Fricke Lara , Schilling Tobias , Glasmacher Birgit
Published: January 2023

Magnesium is a promising metal for resorbable cardiovascular implants due to its high biocompatibility, high corrosion tendency, and mechanical properties. However, adapting its corrosion rate to the physiological healing processes is required to ascertain a safe graft function. A protective polymeric layer is supposed to slow down the corrosion rate of magnesium. Additionally, coatings can improve the host’s tissue interaction with the implant by implementing the local delivery of antibiotic drugs and growth or cell adhesion factors. However, little is known about the interaction of polymer-based coatings, their degradation, and magnesium corrosion. This study examines the corrosion mechanism of magnesium protected by spin coatings and electrospun fiber coatings under physiological conditions. Pure magnesium specimens were coated with polycaprolactone (PCL). The corrosion of the coated magnesium was evaluated using an immersion test in simulated body fluid. Spin coatings provided efficient protection against corrosive attacks and a significantly lower corrosion rate by 75% compared to uncoated magnesium. In contrast, fiber coatings did not provide relevant corrosion protection. On the other hand, magnesium corrosion caused the accelerated degradation of the PCL layer. A reliable and safe implant function is vital, especially in cardiovascular applications. Magnesium coating, therefore, should be carried out with spin coatings.
Synthesis of Magnetron-Sputtered TiN Thin-Films on Fiber Structures for Pulsed-Laser Emission and Refractive-Index Sensing Applications at 1550 nm
Authors: Ramírez Omar Gaspar , Méndez Manuel García , Tamayo Ricardo Iván Álvarez , Cortés Patricia Prieto
Published: January 2023

In this work, a set of titanium nitrides thin-films was synthesized with the technique of reactive RF and DC magnetron-sputtering. To demonstrate the versatility and effectiveness of the deposition technique, thin films were deposited onto different fiber structures varying the deposition parameters for optical applications as saturable absorbers in passively q-switched fiber lasers and as lossy mode resonance fiber refractometers. After deposition, optical and electronical properties of samples were characterized by UV–Vis and XPS spectroscopies, respectively. Samples presented coexisting phases of Ti nitride and oxide, where the nitride phase was non-stoichiometric metallic-rich, with a band gap in the range of Eg = 3.4–3.7 eV. For all samples, glass substrates were used as templates, and on top of them, optical fibers were mounted to be covered with their respective titanium compounds.
Polyphenols in Health and Disease: Gut Microbiota, Bioaccessibility, and Bioavailability
Authors: Bié Joaquim , Sepodes Bruno , Fernandes Pedro C. B. , Ribeiro Maria H. L.
Published: January 2023

Polyphenolic compounds (PC) are among the most abundant secondary metabolites in nature. They are widely distributed in the world and can be found in fruits, cereals, tea, coffee, and beverages. Due to their structural diversity, polyphenols have many different properties and biological effects. They are resistant to the acid of the gastric tract, and very few are hydrolysed or absorbed in the stomach. Significant portions of ingested polyphenols reach the large intestine and interact with the local bacteria, the so-called gut microbiota. Epidemiological studies confirm that moderate and prolonged intake of foods rich in polyphenols could prevent the development of cancer and chronic diseases, such as cardiovascular, neurodegenerative, type 2 diabetes, and obesity. The current work aims to provide an updated overview on the nature and occurrence of polyphenols, quantification methods, bioaccessibility and bioavailability, and impact on human health, namely through interactions with the gut microbiota.
High-Q Slow Sound Mode in a Phononic Fishbone Nanobeam Using an Acoustic Potential Well Cavity
Authors: Tsai Ying-Pin , Lin Bor-Shyh , Hsiao Fu-Li
Published: January 2023

Phononic crystals and phononic metamaterials are popular structures for manipulating acoustic waves with artificially arranged units that have different elastic constants. These structures are also used in acousto-optic coupling and optomechanical structures. In such research, a 1-D nanobeam containing a cavity region sandwiched by two mirror regions is one of the most common designs. However, searching bandgaps for suitable operation modes and the need for the mirror region are limitations in the device design. Therefore, we introduce the slow sound mode as the operating acoustic mode and use an acoustic potential well to further trap the phonons in the cavity. Three types of structures are introduced to investigate the effect of the potential well. The products of the mode frequencies and the quality factors of the modes are used to demonstrate the performance of the structures. The displacement field and the strain field show the concentrated slow sound modes of the potential wells and produce high quality factors.
New Liquid Crystalline Elastomeric Films Containing a Smectic Crosslinker: Chemical and Physical Properties
Authors: Resetic Andraz , Milavec Jerneja , Bubnov Alexej , Pociecha Damian , Hamplova Vera , Gorecka Ewa , Zalar Bostjan , Domenici Valentina
Published: January 2023

Side-chain liquid crystal elastomers (SC-LCEs) have been designed by using a new smectic crosslinker. Two types of monodomain films were prepared based on polysiloxane chains, with a different relative concentration of both crosslinker and mesogenic comonomers. The mesomorphic behavior of the two SC-LCE systems was investigated by differential scanning calorimetry and polarized optical microscopy showing a different mesomorphic behavior: in one case, we obtained a nematic SC-LCE film, in the other case, a Smectic A SC-LCE film. In both systems, the mesophases were stable in a wide temperature range. Moreover, the SC-LCE films possess a relatively high orientation at room temperature. The physical-chemical properties, such as the local orientational ordering, structural organization, and dynamics of SC-LCEs’ constituents were studied by means of static and dynamic 2H NMR experiments, small-angle X-ray, and wide-angle X-ray diffractions. The relevant physical properties, such as the thermo-elastic and thermo-mechanic behaviors, are reported and discussed in view of the practical applications.
Structural and Luminescence Properties of Cu(I)X-Quinoxaline under High Pressure (X = Br, I)
Authors: Gonzalez-Platas Javier , Rodriguez-Mendoza Ulises R. , Aguirrechu-Comeron Amagoia , Hernandez-Molina Rita R. , Turnbull Robin , Rodriguez-Hernandez Placida , Muñoz Alfonso
Published: January 2023

A study of high-pressure single-crystal X-ray diffraction and luminescence experiments together with ab initio simulations based on the density functional theory has been performed for two isomorphous copper(I) halide compounds with the empirical formula [C8H6Cu2X2N2] (X = Br, I) up to 4.62(4) and 7.00(4) GPa for X-ray diffraction and 6.3(4) and 11.6(4) GPa for luminescence, respectively. An exhaustive study of compressibility has been completed by means of determination of the isothermal equations of state and structural changes with pressure at room temperature, giving bulk moduli of K0 = 14.4(5) GPa and K′0 = 7.7(6) for the bromide compound and K0 = 13.0(2) GPa and K′0 = 7.4(2) for the iodide compound. Both cases exhibited a phase transition of second order around 3.3 GPa that was also detected in luminescence experiments under the same high-pressure conditions, wherein redshifts of the emission bands with increasing pressure were observed due to shortening of the Cu–Cu distances. Additionally, ab initio studies were carried out which confirmed the results obtained experimentally, although unfortunately, the phase transition was not predicted.
Automated Hypertension Detection Using ConvMixer and Spectrogram Techniques with Ballistocardiograph Signals
Authors: Ozcelik Salih T. A. , Uyanık Hakan , Deniz Erkan , Sengur Abdulkadir
Published: January 2023

Blood pressure is the pressure exerted by the blood in the veins against the walls of the veins. If this value is above normal levels, it is known as high blood pressure (HBP) or hypertension (HPT). This health problem which often referred to as the “silent killer” reduces the quality of life and causes severe damage to many body parts in various ways. Besides, its mortality rate is very high. Hence, rapid and effective diagnosis of this health problem is crucial. In this study, an automatic diagnosis of HPT has been proposed using ballistocardiography (BCG) signals. The BCG signals were transformed to the time-frequency domain using the spectrogram method. While creating the spectrogram images, parameters such as window type, window length, overlapping rate, and fast Fourier transform size were adjusted. Then, these images were classified using ConvMixer architecture, similar to vision transformers (ViT) and multi-layer perceptron (MLP)-mixer structures, which have attracted a lot of attention. Its performance was compared with classical architectures such as ResNet18 and ResNet50. The results obtained showed that the ConvMixer structure gave very successful results and a very short operation time. Our proposed model has obtained an accuracy of 98.14%, 98.79%, and 97.69% for the ResNet18, ResNet50, and ConvMixer architectures, respectively. In addition, it has been observed that the processing time of the ConvMixer architecture is relatively short compared to these two architectures.