bluuebunny/crossref_metadata_2025 huggingface dataset:
Loss of Serum Glucocorticoid-Inducible Kinase 1 SGK1 Worsens Malabsorption and Diarrhea in Microvillus Inclusion Disease (MVID)
Authors: Ahsan Md Kaimul , dos Reis Diego Carlos , Barbieri Andrea , Sumigray Kaelyn D. , Nottoli Timothy , Salas Pedro J. , Ameen Nadia A.
Published: July 2022

Microvillus inclusion disease (MVID), a lethal congenital diarrheal disease, results from loss of function mutations in the apical actin motor myosin VB (MYO5B). How loss of MYO5B leads to both malabsorption and fluid secretion is not well understood. Serum glucocorticoid-inducible kinase 1 (SGK1) regulates intestinal carbohydrate and ion transporters including cystic fibrosis transmembrane conductance regulator (CFTR). We hypothesized that loss of SGK1 could reduce CFTR fluid secretion and MVID diarrhea. Using CRISPR-Cas9 approaches, we generated R26CreER;MYO5Bf/f conditional single knockout (cMYO5BKO) and R26CreER;MYO5Bf/f;SGK1f/f double knockout (cSGK1/MYO5B-DKO) mice. Tamoxifen-treated cMYO5BKO mice resulted in characteristic features of human MVID including severe diarrhea, microvillus inclusions (MIs) in enterocytes, defective apical traffic, and depolarization of transporters. However, apical CFTR distribution was preserved in crypts and depolarized in villus enterocytes, and CFTR high expresser (CHE) cells were observed. cMYO5BKO mice displayed increased phosphorylation of SGK1, PDK1, and the PDK1 target PKCι in the intestine. Surprisingly, tamoxifen-treated cSGK1/MYO5B-DKO mice displayed more severe diarrhea than cMYO5BKO, with preservation of apical CFTR and CHE cells, greater fecal glucose and reduced SGLT1 and GLUT2 in the intestine. We conclude that loss of SGK1 worsens carbohydrate malabsorption and diarrhea in MVID.
It Is Time to Focus on “Segmental Remodeling” with Validated Biomarkers as “Stressed Heart Morphology” in Prevention of Heart Failure
Authors: Yalcin Fatih , Garcia Mario J.
Published: July 2022

In cardiovascular medicine, hemodynamic stress with hypertension is a major risk [...]
Non-Invasive Detection of a De Novo Frameshift Variant of STAG2 in a Female Fetus: Escape Genes Influence the Manifestation of X-Linked Diseases in Females
Authors: Provenzano Aldesia , La Barbera Andrea , Lai Francesco , Perra Andrea , Farina Antonio , Cariati Ettore , Zuffardi Orsetta , Giglio Sabrina
Published: July 2022

Background: We report on a 20-week-old female fetus with a diaphragmatic hernia and other malformations, all of which appeared after the first-trimester ultrasound. Methods and Results: Whole trio exome sequencing (WES) on cell-free fetal DNA (cff-DNA) revealed a de novo frameshift variant of the X-linked STAG2 gene. Loss-of-function (LoF) STAG2 variants cause either holoprosencephaly (HPE) or Mullegama–Klein–Martinez syndrome (MKMS), are de novo, and only affect females, indicating male lethality. In contrast, missense mutations associate with milder forms of MKMS and follow the classic X-linked recessive inheritance transmitted from healthy mothers to male offspring. STAG2 has been reported to escape X-inactivation, suggesting that disease onset in LoF females is dependent on inadequate dosing for at least some of the transcripts, as is the case with a part of the autosomal dominant diseases. Missense STAG2 variants produce a quantity of transcripts, which, while resulting in a different protein, leads to disease only in hemizygous males. Similar inheritance patterns are described for other escapee genes. Conclusions: This study confirms the advantage of WES on cff-DNA and emphasizes the role of the type of the variant in X-linked disorders.
Insights into Teacher Beliefs and Practice in Primary-School EFL in France
Authors: Whyte Shona , Wigham Ciara R. , Younès Nathalie
Published: July 2022

Teacher beliefs affect choices of methods, representations of learning, and classroom practice, and are important in understanding primary EFL teaching in France, where language teaching has been a compulsory subject entrusted to generalist class teachers for 20 years. This quantitative study explores questionnaire data from 254 primary teachers, associating teacher beliefs and classroom practice. With respect to views of language teaching and learning, the study reveals a three-way division of teachers between grammar-oriented teaching (PPP), communicative-language teaching (CLT), and ‘sceptical’ teachers. The PPP (n = 72) group employed the smallest range of teaching activities and rarely taught older pupils. The CLT group (n = 60) tended to have higher English proficiency and more in-service training and offered the widest range of oral activities. The sceptical group (n = 85) took no strong theoretical position, had lower English proficiency, and focused on listening and speaking skills. We found no correlation between teacher age and language learning beliefs or teaching practices. However, teachers who offered a wider range of activities in any of the five competences tended to have more in-service training and higher English proficiency. Further correlations were found between oral language teaching and technology integration, and written language teaching and teaching experience. The paper concludes with links to previous teacher cognition research and suggestions for teacher education.
Pathogenesis of Distal Symmetrical Polyneuropathy in Diabetes
Authors: Smith Sasha , Normahani Pasha , Lane Tristan , Hohenschurz-Schmidt David , Oliver Nick , Davies Alun Huw
Published: July 2022

Distal symmetrical polyneuropathy (DSPN) is a serious complication of diabetes associated with significant disability and mortality. Although more than 50% of people with diabetes develop DSPN, its pathogenesis is still relatively unknown. This lack of understanding has limited the development of novel disease-modifying therapies and left the reasons for failed therapies uncertain, which is critical given that current management strategies often fail to achieve long-term efficacy. In this article, the pathogenesis of DSPN is reviewed, covering pathogenic changes in the peripheral nervous system, microvasculature and central nervous system (CNS). Furthermore, the successes and limitations of current therapies are discussed, and potential therapeutic targets are proposed. Recent findings on its pathogenesis have called the definition of DSPN into question and transformed the disease model, paving the way for new research prospects.
Searching New Solutions for NiTi Sensors through Indirect Additive Manufacturing
Authors: Carreira Pedro , Gatões Daniel , Alves Nuno , Ramos Ana Sofia , Vieira Maria Teresa
Published: July 2022

Shape Memory Alloys (SMAs) can play an essential role in developing novel active sensors for self-healing, including aeronautical systems. However, the NiTi SMAs available in the market are almost limited to wires, small sheets, and coatings. This restriction is mainly due to the difficulty in processing NiTi through conventional processes. Thus, the objective of this study is to evaluate the potential of one of the most promising routes for NiTi additive manufacturing—material extrusion (MEX). Optimizing the different steps during processing is mandatory to avoid brittle secondary phases formation, such as Ni3Ti. The prime NiTi powder is prealloyed, but it also contains NiTi2 and Ni as secondary phases. The present study highlights the role of Ni and NiTi2, with the later having a melting temperature (Tm = 984 °C) lower than the NiTi sintering temperature, thus allowing a welcome liquid phase sintering (LPS). Nevertheless, the reaction of the liquid phase with the Ni phase could contribute to the formation of brittle intermetallic compounds, particularly around NiTi and NiTi2 phases, affecting the final structural properties of the 3D object. The addition of TiH2 to the virgin prealloyed NiTi powder was also studied and revealed the non-formation of Ni3Ti for a specific composition. The balancing addition of extra Ni revealed priority in the Ni3Ti appearance, emphasizing the role of Ni. Feedstocks extruded (filaments) and green strands (layers), before and after debinding & sintering, were used as homothetic of 3D objects for evaluation of defects (microtomography), microstructures, and mechanical properties. The composition of prealloyed powder with 5 wt.% TiH2 addition after sintering showed a homogeneous matrix with the NiTi2 second phase uniformly dispersed.
Time-Dependent Seismic Fragility of Typical Concrete Girder Bridges under Chloride-Induced Corrosion
Authors: Liu Xiaoxiao , Zhang Wenbin , Sun Peng , Liu Ming
Published: July 2022

Recent studies highlighted the importance of the combined effects of prestress loss and corrosion deterioration for concrete girder bridge structures when the effect of damage on the performance level is estimated. The multi-deterioration mechanisms connected with chloride erosion include the cross-sectional area loss of longitudinal bars and stirrups, the reduction in the ductility, the decrease in the strength of steels and the strength loss of concrete in RC columns. For the corroded RC columns and corroded elastomeric bridge bearings, analytical models of the material degradation phenomena were employed for performing the probabilistic seismic performance analysis, which could obtain the system seismic fragility of aging bridges by considering the failure functionality of multiple correlated components (e.g., columns, bearings). The combined effects of prestress loss and cracking were also considered when developing time-dependent system seismic fragility functions. Here, a typical multi-span reinforced concrete girder bridge was used as a case study for studying the time-variant seismic performance. The results revealed the importance of the joint effects of the multi-deterioration mechanisms when modeling the time-dependent seismic fragility of aging bridge systems, as well as the significance of considering the combined effects of prestress loss and cracking.
Host–Bacterial Interactions: Outcomes of Antimicrobial Peptide Applications
Authors: Alkatheri Asma Hussain , Yap Polly Soo-Xi , Abushelaibi Aisha , Lai Kok-Song , Cheng Wan-Hee , Lim Swee-Hua Erin
Published: July 2022

The bacterial membrane is part of a secretion system which plays an integral role to secrete proteins responsible for cell viability and pathogenicity; pathogenic bacteria, for example, secrete virulence factors and other membrane-associated proteins to invade the host cells through various types of secretion systems (Type I to Type IX). The bacterial membrane can also mediate microbial communities’ communication through quorum sensing (QS), by secreting auto-stimulants to coordinate gene expression. QS plays an important role in regulating various physiological processes, including bacterial biofilm formation while providing increased virulence, subsequently leading to antimicrobial resistance. Multi-drug resistant (MDR) bacteria have emerged as a threat to global health, and various strategies targeting QS and biofilm formation have been explored by researchers worldwide. Since the bacterial secretion systems play such a crucial role in host–bacterial interactions, this review intends to outline current understanding of bacterial membrane systems, which may provide new insights for designing approaches aimed at antimicrobials discovery. Various mechanisms pertaining interaction of the bacterial membrane with host cells and antimicrobial agents will be highlighted, as well as the evolution of bacterial membranes in evasion of antimicrobial agents. Finally, the use of antimicrobial peptides (AMPs) as a cellular device for bacterial secretion systems will be discussed as emerging potential candidates for the treatment of multidrug resistance infections.
In Situ X-ray Radiography and Computational Modeling to Predict Grain Morphology in β-Titanium during Simulated Additive Manufacturing
Authors: Jasien Chris , Saville Alec , Becker Chandler Gus , Klemm-Toole Jonah , Fezzaa Kamel , Sun Tao , Pollock Tresa , Clarke Amy J.
Published: July 2022

The continued development of metal additive manufacturing (AM) has expanded the engineering metallic alloys for which these processes may be applied, including beta-titanium alloys with desirable strength-to-density ratios. To understand the response of beta-titanium alloys to AM processing, solidification and microstructure evolution needs to be investigated. In particular, thermal gradients (Gs) and solidification velocities (Vs) experienced during AM are needed to link processing to microstructure development, including the columnar-to-equiaxed transition (CET). In this work, in situ synchrotron X-ray radiography of the beta-titanium alloy Ti-10V-2Fe-3Al (wt.%) (Ti-1023) during simulated laser-powder bed fusion (L-PBF) was performed at the Advanced Photon Source at Argonne National Laboratory, allowing for direct determination of Vs. Two different computational modeling tools, SYSWELD and FLOW-3D, were utilized to investigate the solidification conditions of spot and raster melt scenarios. The predicted Vs obtained from both pieces of computational software exhibited good agreement with those obtained from in situ synchrotron X-ray radiography measurements. The model that accounted for fluid flow also showed the ability to predict trends unobservable in the in situ synchrotron X-ray radiography, but are known to occur during rapid solidification. A CET model for Ti-1023 was also developed using the Kurz–Giovanola–Trivedi model, which allowed modeled Gs and Vs to be compared in the context of predicted grain morphologies. Both pieces of software were in agreement for morphology predictions of spot-melts, but drastically differed for raster predictions. The discrepancy is attributable to the difference in accounting for fluid flow, resulting in magnitude-different values of Gs for similar Vs.
Effect of the Fracturing Degree of the Source Rock on Rock Avalanche River-Blocking Behavior Based on the Coupled Eulerian-Lagrangian Technique
Authors: Bao Yiding , Chen Jianping , Zhang Weifeng , Li Yuchao , Li Zhihai , Du Ni
Published: July 2022

In this study, the effect of the fracturing degree of the source rock on rock avalanche river-blocking behavior was investigated. The study included the analysis of mass movement behavior, impulse wave behavior, and the formation of landslide dams. The study included a series of simulations of rock avalanche river-blocking based on the coupled Eulerian-Lagrangian (CEL) technique. Prior to the simulation, a water column collapse model was applied to validate the use of the CEL technique on fluid-structure interaction, and to calibrate the material parameters. The source rock in the rock avalanche simulation was cut by different groups of structural planes, with the number of 0 × 0 × 0, 1 × 1 × 1, 4 × 4 × 4, 9 × 9 × 9, 14 × 14 × 14, 19 × 19 × 19 in each dimension, respectively, to represent different fracturing degrees, on the premise of the same volume and shape of the source rock. The simulation results showed that the sliding mass exhibited structure stabilization, such that the structure of the sliding mass gradually stabilized to a steady status over time, in the mass movement process. The structure stabilization made the center of the sliding mass constantly decrease, and provided a higher speed of movement for the rock avalanches with higher fracturing degrees of the source rock. As for the impulse wave behavior, with the increase in the fracturing degree of the source rock, the maximum kinetic energy of the water decreased, and the maximum height and propagation speed of the impulse waves decreased, which indicated that the maximum height and the propagation speed of the impulse waves were positively correlated with the maximum kinetic energy of the water. In regard to the formation of the landslide dams, when the fracturing degree of the source rock was low, the shape of the landslide dam was very different. With the increase of the fracturing degree of the source rock, the shapes of the landslide dams stabilized, and varied slightly after the fracturing degree of the source rock reached a threshold value.
Numerical Study on Mechanical Properties of the Freezing–Thawing Cycle of Tailings Based on Particle Discrete Element Method
Authors: Huang Gang , Yang Yunqin , Liu Mingyu , Zhang Jianhua , Liu Faping , Mwangi Akisa David , Ye Haiwang
Published: July 2022

To study the effects of the number of freezing–thawing cycles (F-T cycles), the dry density, and the average particle diameter on the mechanical properties of tailings, the calibration laws of the fine-scale parameters in the discrete particle element numerical simulation software PFC2D(Particle Flow Code) were first tested, and then pre-experiments were conducted in the form of orthogonal tests. Finally, according to the results of the pre-experiments and the analysis of the pre-experimental results by SPSS (Statistical Product Service Solutions) software, uniaxial tests were carried out for different numbers of freeze–thaw cycles, different dry densities, and different average particle sizes. The tailings specimens were subjected to uniaxial compression simulations. The results showed that (1) the uniaxial compressive strength of the tailings specimens decreased with each freeze–thaw cycle, and stabilized after seven freeze–thaw cycles. (2) With a greater number of freeze–thaw actions, the porosity of the tailings increased after freeze–thawing. The peak of porosity was much higher than that of the models with fewer than seven freeze–thaw actions. (3) The contact number of tailings specimens showed a significant decrease after the number of freeze–thaw cycles reached seven. However, the amount of exposure was not the main factor affecting the strength of tailings (4). As the number of freeze–thaws increased, the tailings model was more prone to stress concentration. Previously, PFC software has been applied to tailings simulation studies, and this study verifies the feasibility of this method. This research is able to offer a reference for studying the mechanical property changes of tailings in the cold highland area.
Magnesium Status and Ca/Mg Ratios in a Series of Children and Adolescents with Chronic Diseases
Authors: Escobedo-Monge Marlene Fabiola , Barrado Enrique , Parodi-Román Joaquín , Escobedo-Monge María Antonieta , Torres-Hinojal María Carmen , Marugán-Miguelsanz José Manuel
Published: July 2022

Magnesium (Mg) is an essential divalent cation involved in various enzymatic reactions that regulate vital biological functions. The main goal was to evaluate Mg status and its association with nutritional indicators in 78 children and adolescents with chronic diseases. We assessed anthropometric, biochemical, diet, body composition, and bone densitometry valuations. Serum Mg and Ca levels were determined using the standardized method and diet calcium (Ca) and Mg consumption by a prospective 72 h diet survey. Mean serum Ca (9.9 mg/dL), Mg (2.08 mg/dL) dietary Ca (102% DRI: Dietary Reference Intake), and Mg intake (105% DRI) were normal. A total of 45% had hypomagnesemia, 12% had hypermagnesemia, and 26% and 24% had inadequate and high Mg intake, respectively. Only 6% of patients had poor Mg intake and hypomagnesemia, and 54% and 90% of our series had an elevated serum Ca/Mg ratio > 4.70 (mean 4.79) and a low Ca/Mg intake ratio < 1.70 (mean 1.06), respectively. Both Ca/Mg ratios were linked with the risk of developing other chronic conditions such as cardiovascular disease, type 2 diabetes, syndrome metabolic, and even several cancers. Therefore, 79% of children and adolescents with chronic diseases were at elevated risk of having abnormal Mg status and developing other chronic illnesses.
Molecular Alterations Caused by Alcohol Consumption in the UK Biobank: A Mendelian Randomisation Study
Authors: O’Farrell Felix , Jiang Xiyun , Aljifri Shahad , Pazoki Raha
Published: July 2022

Alcohol consumption is associated with the development of cardiovascular diseases, cancer, and liver disease. The biological mechanisms are still largely unclear. Here, we aimed to use an agnostic approach to identify phenotypes mediating the effect of alcohol on various diseases. Methods: We performed an agnostic association analysis between alcohol consumption (red and white wine, beer/cider, fortified wine, and spirits) with over 7800 phenotypes from the UK biobank comprising 223,728 participants. We performed Mendelian randomisation analysis to infer causality. We additionally performed a Phenome-wide association analysis and a mediation analysis between alcohol consumption as exposure, phenotypes in a causal relationship with alcohol consumption as mediators, and various diseases as the outcome. Results: Of 45 phenotypes in association with alcohol consumption, 20 were in a causal relationship with alcohol consumption. Gamma glutamyltransferase (GGT; β = 9.44; 95% CI = 5.94, 12.93; Pfdr = 9.04 × 10−7), mean sphered cell volume (β = 0.189; 95% CI = 0.11, 0.27; Pfdr = 1.00 × 10−4), mean corpuscular volume (β = 0.271; 95% CI = 0.19, 0.35; Pfdr = 7.09 × 10−10) and mean corpuscular haemoglobin (β = 0.278; 95% CI = 0.19, 0.36; Pfdr = 1.60 × 10−6) demonstrated the strongest causal relationships. We also identified GGT and physical inactivity as mediators in the pathway between alcohol consumption, liver cirrhosis and alcohol dependence. Conclusion: Our study provides evidence of causality between alcohol consumption and 20 phenotypes and a mediation effect for physical activity on health consequences of alcohol consumption.
Specific Strains of Faecalibacterium prausnitzii Ameliorate Nonalcoholic Fatty Liver Disease in Mice in Association with Gut Microbiota Regulation
Authors: Hu Wenbing , Gao Wenyu , Liu Zongmin , Fang Zhifeng , Wang Hongchao , Zhao Jianxin , Zhang Hao , Lu Wenwei , Chen Wei
Published: July 2022

Evidence linking Faecalibacterium prausnitzii abundance to nonalcoholic fatty liver disease (NAFLD) is accumulating; however, the causal relationship remains obscure. In this study, 12 F. prausnitzii strains were orally administered to high fat diet fed C57BL/6J mice for 12 weeks to evaluate the protective effects of F. prausnitzii on NAFLD. We found that five F. prausnitzii strains, A2-165, LB8, ZF21, PL45, and LC49, significantly restored serum lipid profiles and ameliorated glucose intolerance, adipose tissue dysfunction, hepatic steatosis, inflammation, and oxidative stress in a mouse model of NAFLD. Moreover, two strains, LC49 and LB8, significantly enhanced short-chain fatty acid (SCFA) production and modulated the gut microbiota. Based on the combined analysis of linear discriminant analysis effect size and microbial communities, the core microbiome related to NAFLD comprised Odoribacter, Roseburia, Erysipelatoclostridium, Tyzzerella, Faecalibaculum, Blautia, and Acetatifactor, and the last five genera can be reversed by treatment with the LC49 and LB8 strains. Additionally, the LC49 and LB8 strains enriched Lactobacillus, Ileibacterium, Faecalibacterium, Dubosiella, and Bifidobacterium and downregulated pathways involving carbohydrate metabolism, amino acid metabolism, and fatty acid biosynthesis. Interestingly, LC49 supplementation also upregulated tryptophan metabolism, glutathione metabolism, and valine, leucine, and isoleucine degradation, which might be related to NAFLD prevention. Collectively, F. prausnitzii LC49 and LB8 exerted considerable anti-NAFLD and microbiota-regulating effects, indicating their potential as probiotic agents for NAFLD treatment.
Comment on Wardzinski et al. Mobile Phone Radiation Deflects Brain Energy Homeostasis and Prompts Human Food Ingestion. Nutrients 2022, 14, 339
Authors: Witthöft Michael , Köteles Ferenc , Szemerszky Renáta
Published: July 2022

Wardzinski and colleagues present the findings of an experimental provocation study, in which the effect of a 25 min exposure to radiofrequency electromagnetic field (EMF) emitted by a mobile phone on food consumption is studied [...]
Reply to Witthöft et al. Comment on “Wardzinski et al. Mobile Phone Radiation Deflects Brain Energy Homeostasis and Prompts Human Food Ingestion. Nutrients 2022, 14, 339”
Authors: Wardzinski Ewelina , Jauch-Chara Kamila , Haars Sarah , Melchert Uwe , Scholand-Engler Harald , Oltmanns Kerstin
Published: July 2022

We are somewhat surprised about the extent of the feedback that we received upon our publication [...]
Vitamin A in Skin and Hair: An Update
Authors: VanBuren Christine A. , Everts Helen B.
Published: July 2022

Vitamin A is a fat-soluble micronutrient necessary for the growth of healthy skin and hair. However, both too little and too much vitamin A has deleterious effects. Retinoic acid and retinal are the main active metabolites of vitamin A. Retinoic acid dose-dependently regulates hair follicle stem cells, influencing the functioning of the hair cycle, wound healing, and melanocyte stem cells. Retinoic acid also influences melanocyte differentiation and proliferation in a dose-dependent and temporal manner. Levels of retinoids decline when exposed to ultraviolet irradiation in the skin. Retinal is necessary for the phototransduction cascade that initiates melanogenesis but the source of that retinal is currently unknown. This review discusses new research on retinoids and their effects on the skin and hair.
Effects of Acute Mistletoe (Viscum album L.) Ingestion on Aerobic Exercise Performance
Authors: Goode Emily C. , Van Duser Sarah E. , Rogers Rebecca R. , Williams Tyler D. , Ballmann Christopher G.
Published: July 2022

Mistletoe (Viscum album L.; VA) has been traditionally used in folk medicine to combat fatigue and stress. Evidence has shown that chronic consumption of VA results in an enhancement of oxidative metabolism and exercise performance. However, no studies have investigated how acute VA consumption influences performance. The purpose of this brief report was to investigate the effects of acute VA ingestion on rowing exercise performance. Physically active females were recruited for this study. In a crossover, counterbalanced design, participants completed two trials each with a different treatment: (1) VA (2000 mg) and (2) placebo (PL; gluten-free cornstarch; 2000 mg). A total of 30 minutes prior to exercise, participants consumed their treatment. The participants were familiarized with the rowing ergometer and warmed up for 5 min at 50% of age-predicted heart rate max. Immediately following the warm-up, the participants completed a 2000 m rowing time trial. Blood lactate (La) was obtained with a lactate meter via finger prick before and after exercise. Power output, trial time, heart rate, rating of perceived exertion (RPE), and La were analyzed. The findings revealed no significant differences for the relative power output (p = 0.936), trial time (p = 0.842) or heart rate (p = 0.762). Rating of perceived exertion was lower with VA ingestion (p = 0.027). La was significantly higher post-exercise regardless of treatment (p < 0.001). However, post-exercise La was lower with VA ingestion (p = 0.032). Findings do not support VA as an ergogenic aid but suggest ingestion may alter metabolism resulting in less La formation and subjective fatigue.
Good Response of Advanced Thymic Carcinoma with Low PD-L1 Expression to Chemotherapy plus Pembrolizumab as First-Line Therapy and to Pembrolizumab as Maintenance Therapy: A Case Report
Authors: Nishii Yoichi , Furuhashi Kazuki , Ito Kentaro , Sakaguchi Tadashi , Suzuki Yuta , Fujiwara Kentaro , Yasuma Taro , Kobayashi Tetsu , D’Alessandro-Gabazza Corina N. , Gabazza Esteban C. , Taguchi Osamu , Hataji Osamu
Published: July 2022

Thymic carcinoma is a rare malignant tumor with a poor prognosis. No standard treatment is currently available. The present case was a 64-year-old male smoker with no symptoms referred to our hospital because of abnormal chest radiological findings. The CT study showed a tumor between the anterior mediastinum and the right lung upper lobe, multiple nodular shadows along the right pleura, and pleural effusion. A CT-guided needle biopsy revealed squamous cell carcinoma. However, the differential diagnosis between thymic carcinoma and primary lung cancer was difficult. Treatment with carboplatin, nanoparticle albumin-bound paclitaxel, and pembrolizumab was initiated. The CT scan showed tumor shrinkage and good clinical response after four treatment cycles. Therapy was switched to maintenance therapy with pembrolizumab alone. Imaging studies showed further tumor shrinkage after twelve cycles of maintenance therapy with pembrolizumab. Sixteen cycles of maintenance therapy were continued without performance status deterioration. An abnormal radiological finding was detected after a twelve-month exacerbation-free period. The diagnosis was thymic carcinoma. Treatment with lenvatinib was initiated, and tumor-size reduction was observed. This is the first report of a case showing a successful maintenance therapy with pembrolizumab after effective first-line therapy with a combination of carboplatin-based chemotherapy plus pembrolizumab in advanced thymic carcinoma.
C-Myc Expression in Oral Squamous Cell Carcinoma: Molecular Mechanisms in Cell Survival and Cancer Progression
Authors: Marconi Guya Diletta , Della Rocca Ylenia , Fonticoli Luigia , Melfi Francesco , Rajan Thangavelu Soundara , Carradori Simone , Pizzicannella Jacopo , Trubiani Oriana , Diomede Francesca
Published: July 2022

Oral squamous cell carcinoma (OSCC) represents 90% of malignant epithelial cancer that occurs in the oral cavity. The c-Myc factor is expressed in multiple types of cancer, comprising head and neck squamous cell carcinoma (HNSCC), where it plays a fundamental role in tumor prognosis and in the self-renewal of tumor stem cells. However, the role of c-Myc in controlling OSCC cells is not well-known. The aim of the present study is the evaluation of the biological roles and regulatory mechanism of c-Myc in the pathogenesis of OSCC. Results indicated that c-Myc, c-Jun, Bcl-2, hypoxia inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9), ERK 1/2 and pERK1/2 were overexpressed in a cellular model of squamous cell carcinoma, Cal-27. Doxorubicin (Doxo), a common chemotherapeutic agent, inhibited cell invasion, hypoxia, angiogenesis and inflammation in a cellular model of Cal-27 cells as indicated by downregulation of MMP-9, VEGF, ERK 1/2 and pERK 1/2 as well as promoted apoptosis as evidenced by the downregulation of Bcl-2 protein. This work aimed at underlying the functional relevance of c-Myc in OSCC and the HIF-Myc collaboration by integrating the knowledge on this molecular link in an OSCC tumor microenvironment. The results obtained showed for the first time the vital role of c-Myc in Cal-27 in cell survival/proliferation and tumor growth as well as the negative regulatory effect of Doxo against c-Myc signaling pathway.
The Application of Hollow Fiber Cartridge in Biomedicine
Authors: Hou Yixuan , Mi Kun , Sun Lei , Zhou Kaixiang , Wang Lei , Zhang Lan , Liu Zhenli , Huang Lingli
Published: July 2022

The hollow fiber cartridge has the advantages of good semi-permeability, high surface area to volume ratio, convenient operation, and so on. Its application in chemical analysis, drug in vitro experiment, hemodialysis, and other fields has been deeply studied. This paper introduces the basic structure of hollow fiber cartridge, compares the advantages and disadvantages of a hollow fiber infection model constructed by a hollow fiber cartridge with traditional static model and animal infection model and introduces its application in drug effects, mechanism of drug resistance, and evaluation of combined drug regimen. The principle and application of hollow fiber bioreactors for cell culture and hollow fiber dialyzer for dialysis and filtration were discussed. The hollow fiber cartridge, whether used in drug experiments, artificial liver, artificial kidney, etc., has achieved controllable experimental operation and efficient and accurate experimental results, and will provide more convenience and support for drug development and clinical research in the future.
Towards the Preparation of a Hydrogel from Lyophilisates of the Aloe arborescens Aqueous Extract
Authors: Pawłowicz Kamil , Paczkowska-Walendowska Magdalena , Osmałek Tomasz , Cielecka-Piontek Judyta
Published: July 2022

Aloe gel is a medicinal raw material with proven pharmacological activity. The health-promoting properties of other species of Aloe upon topical application prompted us to develop a formulation for the topical application of A. arborescence species. As a result of the gel preparation from the aqueous lyophilized extracts of three-year-old leaves of A. arborescence, no changes in the composition of the content of aloins A and aloenin A were found. The potential to neutralize free radicals was tested using DPPH and CUPRAC techniques, which confirmed the anti-radical activity of the lyophilisate. Screening of the inhibition of enzymes, the hyperactivity of which is associated with adverse changes in the skin of a pro-inflammatory nature, was performed. Importantly, using the PAMPA SKIN model, the possibility of the penetration of selected extract compounds (aloin A and aloenin A) through the skin was proven. Then, two formulations were prepared based on sodium alginate and hydroxypropyl methylcellulose (HPMC) and the hydrogels were characterized (rheological analysis, drug release profiles, permeability, and stability studies). HPMC-based hydrogel was the one with a targeted release of active substances and greater stability. Aloe arborescens hydrogel matrices seem to be a promising treatment strategy for inflammatory surface damage based on “green technology” at the stage of extract preparation and development of the drug form for topical application.
Synthesis and Rheological Characterization of a Novel Salecan Hydrogel
Authors: Zhang Qinling , Ren Teng , Gan Jing , Sun Lirong , Guan Chenxia , Zhang Qian , Pan Shihui , Chen Hao
Published: July 2022

Salecan (Sal) is a novel microbial polysaccharide. In the present research, thermal treatment was performed to fabricate Sal hydrogel. The effect of Sal concentration on water holding capacity, swelling properties, texture properties, and microstructure of the hydrogels was discussed. It was found that the equilibrium degree of swelling (EDS) of Sal hydrogels was above 1500%, inferred Sal was a highly hydrophilic polysaccharide. As Sal concentration increased from 3.5 to 8.0 wt%, the hardness increased from 0.88 to 2.07 N and the water hold capability (WHC) increased from 91.3% to 98.2%. Furthermore, the internal network structure of Sal hydrogel also became denser and more uniform. Rheological studies suggested that elastic hydrogel formed under the gelation process. All these results demonstrated that Sal hydrogel prepared by thermal treatment had good gelling properties, which opened up a new safe way for the preparation of Sal hydrogel and broadened the application range of Sal.
Nanodevices for the Efficient Codelivery of CRISPR-Cas9 Editing Machinery and an Entrapped Cargo: A Proposal for Dual Anti-Inflammatory Therapy
Authors: García-Fernández Alba , Vivo-Llorca Gema , Sancho Mónica , García-Jareño Alicia , Ramírez-Jiménez Laura , Barber-Cano Eloísa , Murguía José , Orzáez Mar , Sancenón Félix , Martínez-Máñez Ramón
Published: July 2022

In this article, we report one of the few examples of nanoparticles capable of simultaneously delivering CRISPR-Cas9 gene-editing machinery and releasing drugs for one-shot treatments. Considering the complexity of inflammation in diseases, the synergistic effect of nanoparticles for gene-editing/drug therapy is evaluated in an in vitro inflammatory model as proof of concept. Mesoporous silica nanoparticles (MSNs), able to deliver the CRISPR/Cas9 machinery to edit gasdermin D (GSDMD), a key protein involved in inflammatory cell death, and the anti-inflammatory drug VX-765 (GSDMD45CRISPR-VX-MSNs), were prepared. Nanoparticles allow high cargo loading and CRISPR-Cas9 plasmid protection and, thus, achieve the controlled codelivery of CRISPR-Cas9 and the drug in cells. Nanoparticles exhibit GSDMD gene editing by downregulating inflammatory cell death and achieving a combined effect on decreasing the inflammatory response by the codelivery of VX-765. Taken together, our results show the potential of MSNs as a versatile platform by allowing multiple combinations for gene editing and drug therapy to prepare advanced nanodevices to meet possible biomedical needs.
Genetic Augmentation of Legume Crops Using Genomic Resources and Genotyping Platforms for Nutritional Food Security
Authors: Salgotra Romesh K. , Stewart Charles Neal
Published: July 2022

Recent advances in next generation sequencing (NGS) technologies have led the surge of genomic resources for the improvement legume crops. Advances in high throughput genotyping (HTG) and high throughput phenotyping (HTP) enable legume breeders to improve legume crops more precisely and efficiently. Now, the legume breeder can reshuffle the natural gene combinations of their choice to enhance the genetic potential of crops. These genomic resources are efficiently deployed through molecular breeding approaches for genetic augmentation of important legume crops, such as chickpea, cowpea, pigeonpea, groundnut, common bean, lentil, pea, as well as other underutilized legume crops. In the future, advances in NGS, HTG, and HTP technologies will help in the identification and assembly of superior haplotypes to tailor the legume crop varieties through haplotype-based breeding. This review article focuses on the recent development of genomic resource databases and their deployment in legume molecular breeding programmes to secure global food security.
Morphological and Physiological Indicators for Screening Cell Lines with High Potential for Somatic Embryo Maturation at an Early Stage of Somatic Embryogenesis in Pinus Koraiensis
Authors: Peng Chunxue , Gao Fang , Wang Hao , Tretyakova Iraida Nikolaevna , Nosov Alexander Mikhaylovich , Shen Hailong , Yang Ling
Published: July 2022

Many cell lines in the embryogenic callus cannot produce somatic embryos (SEs) even if they meet the optimal SE maturation culture conditions during conifer somatic embryogenesis. This phenomenon hinders the progress of the industrial-scale reproduction of conifers. Therefore, there is an urgent need to obtain morphological and physiological markers to screen embryogenic calli in response to SE maturation conditions. To detect cell lines with high somatic embryogenesis potential during the proliferation process, we counted the number of pro-embryos and early SEs (ESEs) in different cell lines and storage substances, endogenous hormones, and polyamine contents. The results showed that the yield of P. koraiensis SEs was heavily dependent on genotype (p = 0.001). There were high levels of PE III (pro-embryo III) number, ESE number, and soluble protein content, in the response cell lines (R cell lines), which were 1.6-, 3-, and 1.1-fold those of the obstructive cell lines (B cell lines), respectively. The B cell line had high levels of starch, auxin (IAA), Put, Spd, and putrescine: spermine (Put: Spm) compared to the R cell line. In addition, the numbers of PE III, ESEs, and soluble protein content were significantly positively correlated with SE yield. In contrast, the contents of starch, abscisic acid (ABA), Put, Spm, and Spd were significantly negatively correlated with SE yield. To ensure the accuracy of the results, we used nine cell lines to test the results. The PE III and ESE numbers and the Spm and Spd contents were positively correlated with SE yield, while the levels of starch, ABA, IAA, Put: Spd, and Put: Spm were negatively correlated with SE yield. Thus, we recommend using high PE III and ESEs as morphological indicators and low levels of starch, IAA, ABA, and Put: Spm as physiological markers to screen cell lines with a high somatic embryogenesis potential. In addition, we also found that the relationship between Spd, Spm, and SE yield was opposite in the two experimental results. Therefore, we speculate that the differences in Spd and Spm content are mainly affected by genotype. In conclusion, this study obtained the morphological and physiological markers of some high-somatic embryogenic cell lines by comparing the differences between nine somatic embryogenic cell lines. Our results can guide the improvement of conifer somatic embryogenesis technology and can provide a theoretical basis for accelerating the application of biotechnology in large-scale artificial breeding.
Hirsutanone Isolated from the Bark of Alnus japonica Attenuates Melanogenesis via Dual Inhibition of Tyrosinase Activity and Expression of Melanogenic Proteins
Authors: Uto Takuhiro , Tung Nguyen Huu , Shoyama Yukihiro
Published: July 2022

Hirsutanone (Hir) and oregonin (Ore) are diarylheptanoids isolated from the bark of Alnus japonica. In this study, we investigated the anti-melanogenic activity of Hir and Ore in B16-F1 murine melanoma and normal human epidermal melanocytes (HEMn-DP) and elucidated the mechanisms of action. In B16-F1 cells, Hir and Ore suppressed melanin synthesis induced by α-melanocyte-stimulating hormone (α-MSH) without cytotoxicity. The inhibitory effect of Hir on melanin synthesis was much stronger than that of Ore. In addition, Hir reduced melanin content in HEMn-DP cells. As tyrosinase is a key enzyme in melanin synthesis, the effect of Hir on tyrosinase activity was assessed. The results demonstrated that Hir partially decreased tyrosinase activity and intracellular tyrosinase activity. Moreover, Hir suppressed the protein expression of melanogenic enzymes, including tyrosinase, tyrosinase-related protein (TRP)-1, and TRP-2, leading to reduced melanin biosynthesis. Hir also led to the suppression of cAMP response element-binding protein (CREB) phosphorylation and microphthalmia-associated transcription factor (MITF) expression, which control the expression of melanogenic enzymes. These results suggest that Hir suppressed melanin synthesis by dual inhibition of tyrosinase activity and the CREB/MITF pathway leading to the expression of melanogenic enzymes and may be a potent cosmetic and therapeutic agent for hyperpigmentation disorders.
Microencapsulation by Spray Drying and Antioxidant Activity of Phenolic Compounds from Tucuma Coproduct (Astrocaryum vulgare Mart.) Almonds
Authors: Ferreira Lindalva Maria de Meneses Costa , Pereira Rayanne Rocha , Carvalho-Guimarães Fernanda Brito de , Remígio Myrth Soares do Nascimento , Barbosa Wagner Luiz Ramos , Ribeiro-Costa Roseane Maria , Silva-Júnior José Otávio Carréra
Published: July 2022

The industrial processing of fruits in the Amazon region, such as tucuma, generates a large amount of coproducts with great nutritional potential. In this work, phenolic compounds from tucuma coproduct almonds were extracted and microencapsulated by spray drying using maltodextrin as the encapsulating agent and verified its antioxidant activity. Phenolic compounds were determined by UV spectroscopy and identified by Ultraefficiency Liquid Chromatography. Antioxidant activity was measured by ABTS and DPPH assay. Thermogravimetric techniques, infrared spectroscopy, scanning electron microscopy, moisture content and water activity were applied to characterize the microparticle. The crude extract and microparticle had total polyphenols of 135.1 mg/g ± 0.078 and 130.5 mg/g ± 0.024, respectively. Caffeic and gallic acids were identified. The crude extract and the microparticle showed good antioxidant activity by ABTS and DPPH assay, justified by the presence of the phenolic compounds found. The microparticle showed spherical and heterogeneous structures and good encapsulation efficiency from the spray drying process using maltodextrin. The results show that the extract of the tucuma almond coproduct can be used as a phenolic compound-rich source and microencapsulated with possible application for functional food production.
A Modified Langmuir Model for Moisture Diffusion in UGFRE of Composite Insulator Considering the Composite Degradation
Authors: Yuan Zhikang , Wang Cheng , Jin Lijun , Tu Youping , Zhang Yingyao , An Zhenlian , Zhao Yongfei
Published: July 2022

Water invasion induced aging and degradation of the unidirectional glass fiber reinforced epoxy resin (UGFRE) rod is inferred as the primary reason for the decay-like fracture of the composite insulator. In this paper, the moisture diffusion processes in the UGFRE from different directions at various test humidities and temperatures are studied. The moisture diffusion of the UGFRE sample obeys the Langmuir diffusion law under the humidity conditions of 53%, 82% and 100% at 40 °C. In deionized water, the moisture diffusion of the UGFRE sample also obeys the Langmuir diffusion law when the invading direction is vertical to the glass fiber. However, when the water invades the UGFRE sample, parallel with the glass fiber, the weight loss caused by composite degradation should not be neglected. A modified Langmuir model, taking Arrhenius Theory and the nonlinear aging characteristic of the composite into consideration, is proposed and can successfully describe the moisture diffusion process. Both the glass fibers and epoxy resin will degrade in the deionized water. The glass fibers show better resistance to degradation than the epoxy resin. The epoxy resin degrades from the glass fiber/epoxy resin interface and become fragments. For composite insulators, the water invasion through the ends should be avoided as far as possible, or the degradation of the UGFRE rod will result in decay-like fracture.
When the Land Sings: Reconstructing Prehistoric Environments Using Evidence from Quaternary Geology and Geomorphology, with Examples Drawn from Fluvial Environments in the Nile and Son Valleys
Authors: Williams Martin
Published: July 2022

Geomorphic evidence from rivers and lakes can help explain past changes in the locations of archaeological sites as well as environmental and climatic changes in their catchment areas. Examples drawn from the Blue and White Nile valleys in northeast Africa and from the Son and Belan valleys in north-central India reveal how Quaternary climatic fluctuations in the headwaters of these rivers are reflected in changes in river channel patterns downstream as well as in the type of sediment transported. Soils and sediments that contain prehistoric and historic artefacts can be analysed to show the type of environment in which the artefacts accumulated. Beds of volcanic ash may preserve former landscapes and their fossil remains and can provide a synchronous time marker against which to assess changes in the archaeological record. The pattern and tempo of past sea level fluctuations has controlled the distribution of coastal archaeological sites and helps to explain the absence of certain Holocene Neolithic sites in southeast Asia. Disturbance of archaeological sites by plants and animals, especially termites in tropical regions, can affect the stratigraphic and chronological integrity of the site.
Jonah in 20th Century Literature
Authors: Tiemeyer Lena-Sofia
Published: July 2022

The biblical book of Jonah has been the subject of multiple literary retellings, ranging from individual poems to whole novels and theatrical dramas. This article focuses on interaction with the book of Jonah in 20th-century world literature, where Jonah becomes our alter ego; he embodies our own struggles with God. I shall highlight three common tropes in the retellings: (1) Several retellings use the character of Jonah to express a person’s failure to escape God’s calling. Others use him to explore the Jewish experience of never being able to run away from being chosen by God. (2) Other retellings turn the trope of “the fleeing Jonah” into “Jonah the refugee”: Jonah is a man whom God abandoned. These retellings stem from Jonah 2:5 (Eng. 2:4] where Jonah expresses how he is cast out from God’s presence. They gain further inspiration from the affinity between the dialogue between God and Jonah in Jonah 4 and that between Cain and God in Gen 4. This intertextuality fashions Jonah as a type for the “wandering Jew.” (3) Yet another set of retellings employs the figure of Jonah to discuss God’s justice and his perceived failure to be unmerciful.