bluuebunny/crossref_metadata_2025 huggingface dataset:
Metallurgical Defects and Roughness Investigation in the Laser Powder Bed Fusion Multi-Scanning Strategy of AlSi10Mg Parts
Authors: Boschetto Alberto , Bottini Luana , Pilone Daniela
Published: June 2024

Laser Powder Bed Fusion is the most attractive additive manufacturing technology for its capability to produce metal components with complex geometry. One of the main drawbacks is the poor surface roughness. In this work, different scan strategies and process parameters were studied and their effect on surface roughness, alloy microstructure, and metallurgical defects were discussed. The results highlighted that only tailored process conditions could combine acceptable roughness and absence of metallurgical defects. For the upskin, it has been seen that, although by increasing the Volumetric Energy Density value the Ra decreases, Volumetric Energy Density values higher than 69 J/mm3 determine meltpool instability with consequent formation of gas defects in the subsurface area. Similarly, by increasing the Linear Energy Density value, the Ra of the lateral surfaces decreases, but above 0.37 J/mm, metallurgical defects form in the subsurface area. This study also highlighted that the proposed process involves only a contained increase of the production times. In fact, the evaluation of the increased production times, related to the adoption of this multi-scanning strategy, is of fundamental importance to consider if the proposed process can be advantageously applied on an industrial scale.
Effect of Cobalt on the Microstructure of Fe-B-Sn Amorphous Metallic Alloys
Authors: Grey Daniel G. , Cesnek Martin , Bujdoš Marek , Miglierini Marcel B.
Published: June 2024

Fe78B15Sn7 and (Fe3Co1)78B15Sn7 amorphous metallic alloys were prepared using the method of planar flow casting. The amorphous nature of ribbons containing 7 at. % Sn was verified by X-ray diffraction. The resulting chemical composition was checked by flame atomic absorption spectroscopy and by mass spectrometry with inductively coupled plasma. The microstructure of the as-quenched metallic glasses was investigated by 57-Fe and 119-Sn Mössbauer spectrometry. The experiments were performed with transmission geometry at 300 K, 100 K, and 4.2 K, and in an external magnetic field of 6 T. The replacement of a quarter of the Fe by Co did not cause significant modifications of the hyperfine interactions in the 57-Fe nuclei. The observed minor variations in the local magnetic microstructure were attributed to alterations in the topological short-range order. However, the in-field 57-Fe Mössbauer spectra indicated a misalignment of the partial magnetic moments. On the other hand, the presence of Co considerably affected the local magnetic microstructure of the 119-Sn nuclei. This was probably due to the higher magnetic moment of Co, which induces transfer fields and polarization effects on the diamagnetic Sn atoms.
Distribution Behavior of Impurities during the Hydrogen Reduction Ironmaking Process
Authors: Wang Hao , Liu Fupeng , Zeng Hong , Liao Jinfa , Wang Jinliang , Lai Chaobin
Published: June 2024

The traditional blast furnace ironmaking process is the most widely used ironmaking process globally, yet it is associated with significant drawbacks, including high energy consumption and carbon emissions. To achieve low-carbon ironmaking, researchers have developed hydrogen ironmaking, which is capable of achieving lower CO2 emissions. Nevertheless, the distribution behavior of impurities has been less studied in the existing research on hydrogen ironmaking. Therefore, in this study, the factors affecting the slag properties and distribution of impurity elements during hydrogen ironmaking were investigated using FactSage, and smelting experiments were carried out. The results show that temperature has the greatest influence on the distribution behavior of the impurities, and excessively elevated temperatures result in the ingress of a significant quantity of impurities into the reduced iron. Reduced iron with a purity of 98.52% was obtained under the conditions of 10%, 10%, 2%, and 2% ratios of CaO, SiO2, MgO, and Al2O3, respectively, a hydrogen flow rate of 12 mL/min, and a temperature of 1400 °C; Lg L Mg, Lg L Al, Lg L Si, and Lg L Ca were 2.72, 2.41, 3.36, and 2.45, respectively (“L” stands for slag-to-metal ratio). The slag was mainly dominated by the silicate, and the iron was mainly lost in the form of mechanical inclusions in the slag. This study will enrich the basic theory of hydrogen ironmaking and is of great significance for the realization of carbon neutralization.
Adaptive Effects of Endocrine Hormones on Metabolism of Macronutrients during Fasting and Starvation: A Scoping Review
Authors: Karimi Reza , Yanovich Alina , Elbarbry Fawzy , Cleven Anita
Published: June 2024

Food deprivation can occur for different reasons. Fasting (<24 h duration) occurs to meet religious or well-being goals. Starvation (>1-day duration) occurs when there is intentional (hunger strike or treatment of a medical condition) or unintentional (anorexia nervosa, drought, epidemic famine, war, or natural disaster) food deprivation. A scoping review was undertaken using the PubMed database to explore 1805 abstracts and review 88 eligible full-text articles to explore the adaptive relationships that emerge between cortisol, insulin, glucagon, and thyroid hormones on the metabolic pathways of macronutrients in humans during fasting and starvation. The collected data indicate that fasting and starvation prime the human body to increase cortisol levels and decrease the insulin/glucagon ratio and triiodothyronine (T3) levels. During fasting, increased levels of cortisol and a decreased insulin/glucagon ratio enhance glycogenolysis and reduce the peripheral uptake of glucose and glycogenesis, whereas decreased T3 levels potentially reduce glycogenolysis. During starvation, increased levels of cortisol and a decreased insulin/glucagon ratio enhance lipolysis, proteolysis, fatty acid and amino acid oxidation, ketogenesis, and ureagenesis, and decreased T3 levels reduce thermogenesis. We present a potential crosstalk between T3 and the above hormones, including between T3 and leptin, to extend their adaptive roles in the metabolism of endogenous macronutrients during food deprivation.
Anomaly-Based Variable Models: Examples of Unusual Track and Extreme Precipitation of Tropical Cyclones
Authors: Qian Weihong , Du Jun , Ai Yang , Leung Jeremy , Liu Yongzhu , Xu Jianjun
Published: June 2024

Tropical cyclones (TCs) can cause severe wind and rain hazards. Unusual TC tracks and their extreme precipitation forecasts have become two difficult problems faced by conventional models of primitive equations. The case study in this paper finds that the numerical computation of the climatological component in conventional models restricts the prediction of unusual TC tracks. The climatological component should be a forcing quantity, not a predictor in the numerical integration of all models. Anomaly-based variable models can overcome the bottleneck of forecast time length or the one-week forecasting barrier, which is limited to less than one week for conventional models. The challenge in extreme precipitation forecasting is how to physically get the vertical velocity. The anomalous moisture stress modulus (AMSM), as an indicator of heavy rainfall presented in this paper, considers the two conditions associated with vertical velocity and anomalous specific humidity in the lower troposphere. Vertical velocity is produced by the orthogonal collision of horizontal anomalous airflows.
A Novel EWOD Platform for Freely Transporting Droplets in Double and Single-Plate Structures
Authors: Chang Yii-Nuoh , Huang Ting-Rui , Yao Da-Jeng
Published: June 2024

This study developed a novel dielectric wetting microfluidic operation platform combining parallel-plate and coplanar-plate regions with a curved surface structure as the connection structure. With the new electrowetting on dielectric (EWOD) platform, “droplet pull-out” has been successfully achieved and viewed as an essential new operation for microfluidics with the dielectric wetting technique. The EWOD system is divided into a PDMS substrate top plate and an indium tin oxide (ITO) glass substrate as a bottom layer on this chip. In the parallel-plate region, the droplets can be generated and transported through the square parallel electrodes; in the single-plate area, the droplets can be pulled out from the parallel structure, transported and mixed through the common grounded coplanar electrodes. In dielectric wetting performance testing, coplanar electrodes can apply a maximum driving force of 31.22 µN to DI water and 13.38 µN to propylene carbonate (PC). This driving force is sufficient to detach the sample from the top cover and pull the sub-droplet from the parallel plate structure for DI water, PC and polyethylene glycol diacrylate (PEGDA) buffer. The novel EWOD system also possesses the advantage of precise volume control for liquid samples; the volume error of the generated droplet can be controlled within 0.1% to 2%.
Microplastic Analysis in Soil Using Ultra-High-Resolution UV–Vis–NIR Spectroscopy and Chemometric Modeling
Authors: Pieniazek Lori Shelton , McKinney Michael L. , Carr Jake A. , Shen Lei
Published: June 2024

The study of microplastics (MPs) in soils is impeded by similarities between plastic and non-plastic particles and the misidentification of MP by current analytical methods such as visual microscopic examination. Soil MPs pose serious ecological and public health risks because of their abundance, persistence, and ubiquity. Thus, reliable identification methods are badly needed for scientific study. One possible solution is UV–Vis–NIR spectroscopy, which has the ability to rapidly identify and quantify concentrations of soil microplastics. In this study, a full-range, field portable spectrometer (350–2500 nm) with ultra-high spectral resolution (1.5 nm, 3.0 nm, and 3.8 nm) identified three types of common plastics: low-density polyethylene (LDPE), polyvinyl chloride (PVC), and polypropylene (PP). Three sets of artificially MP-treated vermiculite soil samples were prepared for model prediction testing and validation: 150 samples for model calibration and 50 samples for model validation. A partial least square regression model using the spectral signatures for quantification of soil and MP mixtures was built with all three plastic polymers. Prediction R2 values of all three polymers showed promising results: polypropylene R2 = 0.943, polyvinyl chloride R2 = 0.983, and polyethylene R2 = 0.957. Our study supports previous work showing that combining ultra-high-resolution UV–Vis–NIR spectrometry with quantitative modeling can improve the accuracy and speed of MP identification and quantification in soil.
Quantification of Feldspar and Quartz Nucleation Delay in a Hydrous Peraluminous Granitic Melt
Authors: Bilodeau Maude , Baker Don R.
Published: June 2024

A modified model based on classical nucleation theory was applied to a natural hydrous peraluminous pegmatite composition and tested against crystallization experiments in order to further investigate the quantification of nucleation delay in felsic melts. Crystallization experiments were performed in a piston-cylinder apparatus at 630 MPa and temperatures between 650 and 1000 °C for durations ranging from 0.3 to 211 h. Experimental run products were investigated by scanning electron microscopy paired with energy dispersive spectroscopy analyses of both crystalline and quenched liquid phases, the results of which were compared to an established theoretical nucleation delay model from the literature. The experiments showed good agreement (within a factor of 5) with the model for quartz, while it showed moderate agreement (within a factor of 10) with the model for sodic feldspar. Other crystals also nucleated, demonstrating abundant features of disequilibrium. Our research further demonstrates the potential of the model to predict nucleation delay, showing promising results for the quantification of the nucleation delay of quartz and feldspar in natural felsic melts, thus adding to previously published studies on hydrous, metaluminous, felsic melts and dry basaltic melts.
Zircon U-Pb Dating, Geochemistry, Lu-Hf Isotope Characteristics, and Geological Significance of Volcanic Rocks in Zhenghe Fozi Mountain National Geopark, Fujian, China
Authors: Chen Nan , Li Dunpeng , Huang Yanna , Fu Yihang , Yang Xiaomin , Wang Hanbin
Published: June 2024

Fozi Mountain National Geopark is located in Zhenghe County in the northern region of Fujian Province, where the volcanic rocks of the Zhaixia Formation of the Shimaoshan Group are exposed. Zircon U-Pb dating and geochemical analysis were carried out to constrain its age and tectonic environment. The results show that three zircon U-Pb dating samples have attained ages of 99.2 ± 1.0 Ma, 99.6 ± 0.8 Ma, and 99.7 ± 2.0 Ma. Volcanic rocks in the core scenic area of Fozi Mountain were formed during the Late Cretaceous period. Elemental analysis showed that these volcanic rocks were dominated by the shoshonite series. They include gray dacite porphyry, grayish-white breccia tuff, volcanic agglomerate, and gray tuffaceous sandstone. These rocks were characterized by high silicon, high alkali content, and rich potassium levels. Lu-Hf isotope analysis of zircons revealed that their εHf(t) values varied from −8.7 to −6.8. The corresponding TDM2 values were primarily distributed in the range of 1.71 Ga to 1.59 Ga. These findings indicated that the magma primarily originated from the partial melting of the Mesoproterozoic crystalline basement, accompanied by a small number of mantle-derived materials. Tectonic environment analysis indicated that these rocks were formed in the post-orogenic intraplate extensional environment, which was associated with the back-arc extension or lithospheric thinning caused by the subduction of the paleo-Pacific plate beneath the Eurasian plate. The formation of these volcanic rocks was attributed to post-orogenic magmatism.
Synergistic Effect of SiO2 and Fe3O4 Nanoparticles in Autophagy Modulation
Authors: Nanda Sitansu Sekhar , Kim Danyeong , Yang Hyewon , An Seong Soo A. , Yi Dong Kee
Published: June 2024

Rapid advancements in nanotechnology have expanded its applications and synergistic impact on modern nanosystems. The comprehensive assessment of nanomaterials’ safety for human exposure has become crucial and heightened. In addition to the characterization of cell proliferation and apoptosis, probing the implication of autophagy is vital for understanding the ramification of nanomaterials. Hence, HEK-293 kidney cells were employed to understand the changes in induction and perturbation of autophagy in cells by iron oxide (Fe3O4) and silica (SiO2) nanoparticles. Interestingly, Fe3O4 worked as a potent modulator of the autophagy process through its catalytic performance, which can develop better than that of SiO2 nanoparticles mechanism, stressing their therapeutic implication in the understanding of cell behaviors. The quantification of reactive oxygen species (ROS) was measured along with the process of autophagy during cell growth. This modulated autophagy will help in cell fate determination in complementary therapy for disease treatment, provide a clinical strategy for future study.
Distinguishing the Charge Trapping Centers in CaF2-Based 2D Material MOSFETs
Authors: Zhao Zhe , Xiong Tao , Gong Jian , Liu Yue-Yang
Published: June 2024

Crystalline calcium fluoride (CaF2) is drawing significant attention due to its great potential of being the gate dielectric of two-dimensional (2D) material MOSFETs. It is deemed to be superior to boron nitride and traditional silicon dioxide (SiO2) because of its larger dielectric constant, wider band gap, and lower defect density. Nevertheless, the CaF2-based MOSFETs fabricated in the experiment still present notable reliability issues, and the underlying reason remains unclear. Here, we studied the various intrinsic defects and adsorbates in CaF2/molybdenum disulfide (MoS2) and CaF2/molybdenum disilicon tetranitride (MoSi2N4) interface systems to reveal the most active charge-trapping centers in CaF2-based 2D material MOSFETs. An elaborate Table comparing the importance of different defects in both n-type and p-type devices is provided. Most impressively, the oxygen molecules (O2) adsorbed at the interface or surface, which are inevitable in experiments, are as active as the intrinsic defects in channel materials, and they can even change the MoSi2N4 to p-type spontaneously. These results mean that it is necessary to develop a high-vacuum packaging process, as well as prepare high-quality 2D materials for better device performance.
Supplementation Strategies for Strength and Power Athletes: Carbohydrate, Protein, and Amino Acid Ingestion
Authors: Bird Stephen P. , Nienhuis Mitch , Biagioli Brian , De Pauw Kevin De , Meeusen Romain
Published: June 2024

It is a common belief amongst strength and power athletes that nutritional supplementation strategies aid recovery by shifting the anabolic/catabolic profile toward anabolism. Factors such as nutrient quantity, nutrient quality, and nutrient timing significantly impact upon the effectiveness of nutritional strategies in optimizing the acute responses to resistance exercise and the adaptive response to resistance training (i.e., muscle growth and strength expression). Specifically, the aim of this review is to address carbohydrates (CHOs), protein (PRO), and/or amino acids (AAs) supplementation strategies, as there is growing evidence suggesting a link between nutrient signaling and the initiation of protein synthesis, muscle glycogen resynthesis, and the attenuation of myofibrillar protein degradation following resistance exercise. Collectively, the current scientific literature indicates that nutritional supplementation strategies utilizing CHO, PRO, and/or AA represents an important approach aimed at enhancing muscular responses for strength and power athletes, primarily increased muscular hypertrophy and enhanced strength expression. There appears to be a critical interaction between resistance exercise and nutrient–cell signaling associated with the principle of nutrient timing (i.e., pre-exercise, during, and post-exercise). Recommendations for nutritional supplementation strategies to promote muscular responses for strength and athletes are provided.
The Relationship between Patient Self-Reported, Pre-Morbid Physical Activity and Clinical Outcomes of Inpatient Treatment in Youth with Anorexia Nervosa: A Pilot Study
Authors: Pech Martina , Correll Christoph U. , Schmidt Janine , Zeeck Almut , Hofmann Tobias , Busjahn Andreas , Haas Verena
Published: June 2024

Links between premorbid physical activity (PA) and disease onset/course in patients with anorexia nervosa (AN) remain unclear. The aim was to assess self-reported PA as a predictor of change in percent median BMI (%mBMI) and length of hospital stay (LOS). Five PA domains were assessed via semi-structured interview in adolescents with AN at hospitalization: premorbid PA in school grades 1-6 (PA1-6); PA before AN onset (PA-pre) and after AN onset (PA-post); new, pathological motivation for PA (PA-new); and high intensity PA (PA-high). Eating disorder psychopathology was measured via the Eating Disorder Examination Questionnaire (EDE-Q), and current PA (steps/day) with accelerometry. PA1-6 was also assessed in healthy controls (HCs). Using stepwise backward regression models, predictors of %mBMI change and LOS were examined. Compared with 22 HCs (age = 14.7 ± 1.3 years, %mBMI = 102.4 ± 12.1), 25 patients with AN (age = 15.1 ± 1.7 years, %mBMI = 74.8 ± 6.0) reported significantly higher PA1-6 (median, AN = 115 [interquartile range IQR = 75;200] min vs. HC = 68 [IQR = 29;105] min; p = 0.017). PA-post was 244 ± 323% higher than PA-pre. PA1-6 was directly associated with PA-pre (p = 0.001) but not with PA-post (p = 0.179) or change in PA-pre to PA-post (p = 0.735). Lower %mBMI gain was predicted by lower baseline %mBMI (p = 0.001) and more PA-high (p = 0.004; r2 = 0.604). Longer LOS was predicted by higher PA-pre (p = 0.003, r2 = 0.368). Self-reported PA may identify a subgroup of youth with AN at risk of less weight gain and prolonged LOS during inpatient treatment for AN.
Evaluation of Nutrition and Performance Parameters in Division 1 Collegiate Athletes
Authors: Shoemaker Marni E. , Dicks Nathan D. , Northrup Megan J. , Daughters Seth W. , Krings Taylor N. , Barry Allison M.
Published: June 2024

Background: Testing and evaluating athletes is necessary and should include performance, body composition, and nutrition. The purpose of this study was to report assessments of dietary intake, V˙O2max, and body composition in D1 collegiate athletes and examine relationships between these assessments. Methods: Dietary intake was assessed with 3-day recalls and compared to recommendations, and body composition was assessed via bioelectrical impedance analysis (BIA) (n = 48). V˙O2max was evaluated using a graded exercise test (GXT) with a verification bout (n = 35). Reliability between “true” V˙O2max and verification was determined. Correlations and regressions were performed. Results: Energy, carbohydrate, and micronutrient intake was lower than recommendations. Mean V˙O2max was 47.3 and 47.4 mL·kg−1·min−1 for GXT and verification, respectively. While correlations were apparent among dietary intake, V˙O2max, and body composition, percent fat-free mass (%FFM) predicted 36% of V˙O2max. Conclusions: Collegiate athletes are not meeting energy and carbohydrate recommendations and exceed fat recommendations. Vitamin D and magnesium were low in all sports, and iron and calcium were low in females. V˙O2max ranged from 35.6 to 63.0 mL·kg−1·min−1, with females below average and males meeting typical values for their designated sport. Assessing D1 athletes can provide guidance for sports dietitians, coaches, and strength and conditioning specialists to track and monitor nutrition in athletes.
Protein Requirements for Maximal Muscle Mass and Athletic Performance Are Achieved with Completely Plant-Based Diets Scaled to Meet Energy Needs: A Modeling Study in Professional American Football Players
Authors: Goldman David M. , Warbeck Cassandra B. , Karlsen Micaela C.
Published: June 2024

American football players consume large quantities of animal-sourced protein in adherence with traditional recommendations to maximize muscle development and athletic performance. This contrasts with dietary guidelines, which recommend reducing meat intake and increasing consumption of plant-based foods to promote health and reduce the risk of chronic disease. The capacity of completely plant-based diets to meet the nutritional needs of American football players has not been studied. This modeling study scaled dietary data from a large cohort following completely plant-based diets to meet the energy requirements of professional American football players to determine whether protein, leucine, and micronutrient needs for physical performance and health were met. The Cunningham equation was used to estimate calorie requirements. Nutrient intakes from the Adventist Health Study 2 were then scaled to this calorie level. Protein values ranged from 1.6–2.2 g/kg/day and leucine values ranged from 3.8–4.1 g/meal at each of four daily meals, therefore meeting and exceeding levels theorized to maximize muscle mass, muscle strength, and muscle protein synthesis, respectively. Plant-based diets scaled to meet the energy needs of professional American football players satisfied protein, leucine, and micronutrient requirements for muscle development and athletic performance. These findings suggest that completely plant-based diets could bridge the gap between dietary recommendations for chronic disease prevention and athletic performance in American football players.
Direct-Acting Antiviral Agents in Prevention of Maternal–Fetal Transmission of Hepatitis C Virus in Pregnancy
Authors: Hartley Christopher , Van Trung , Karnsakul Wikrom
Published: June 2024

Prior to the Food and Drug Administration approval of ledipaspavir/sofosbuvir (Harvoni®) in 2014, the treatment of hepatitis C was interferon plus or minus ribavirin. This treatment had low cure rates for hepatitis C virus and was teratogenic and therefore avoided in pregnant patients. Vertical transmission is the most common transmission of hepatitis C in pediatric patients, whereas medical equipment that was not properly cleaned and sterilized, blood products which were not checked (historically), sharing and reusing syringes and needles, and dialysis are the most common forms of hepatitis C transmission in adults. The treatment of pregnant women with direct-acting antivirals is important because the treatment of pediatric patients cannot begin until three years of age and does not always occur prior to the symptom development of hepatitis C. This review article will include glecaprevir/pibrentasvir (Mayvret®), sofosbuvir/velpatasvir (Epclusa®), and sofosbuvir/velpatasvir plus voxilaprevir (Vosevi®). We aim to review the teratogenic risk of direct-acting antivirals as well as currently published clinical trials and ongoing research on direct-acting antiviral hepatitis C treatment in pregnancy in this publication.
Promising Strategies to Reduce the SARS-CoV-2 Amyloid Deposition in the Brain and Prevent COVID-19-Exacerbated Dementia and Alzheimer’s Disease
Authors: Navolokin Nikita , Adushkina Viktoria , Zlatogorskaya Daria , Telnova Valeria , Evsiukova Arina , Vodovozova Elena , Eroshova Anna , Dosadina Elina , Diduk Sergey , Semyachkina-Glushkovskaya Oxana
Published: June 2024

The COVID-19 pandemic, caused by infection with the SARS-CoV-2 virus, is associated with cognitive impairment and Alzheimer’s disease (AD) progression. Once it enters the brain, the SARS-CoV-2 virus stimulates accumulation of amyloids in the brain that are highly toxic to neural cells. These amyloids may trigger neurological symptoms in COVID-19. The meningeal lymphatic vessels (MLVs) play an important role in removal of toxins and mediate viral drainage from the brain. MLVs are considered a promising target to prevent COVID-19-exacerbated dementia. However, there are limited methods for augmentation of MLV function. This review highlights new discoveries in the field of COVID-19-mediated amyloid accumulation in the brain associated with the neurological symptoms and the development of promising strategies to stimulate clearance of amyloids from the brain through lymphatic and other pathways. These strategies are based on innovative methods of treating brain dysfunction induced by COVID-19 infection, including the use of photobiomodulation, plasmalogens, and medicinal herbs, which offer hope for addressing the challenges posed by the SARS-CoV-2 virus.
Swellable Microneedles in Drug Delivery and Diagnostics
Authors: Omidian Hossein , Dey Chowdhury Sumana
Published: June 2024

This manuscript explores the transformative potential of swellable microneedles (MNs) in drug delivery and diagnostics, addressing critical needs in medical treatment and monitoring. Innovations in hydrogel-integrated MN arrays facilitate controlled drug release, thereby expanding treatment options for chronic diseases and conditions that require precise dosage control. The review covers challenges, such as scalability, patient compliance, and manufacturing processes, as well as achievements in advanced manufacturing, biocompatibility, and versatile applications. Nonetheless, limitations in physiological responsiveness and long-term stability remain, necessitating further research in material innovation and integration with digital technologies. Future directions focus on expanding biomedical applications, material advancements, and regulatory considerations for widespread clinical adoption.
Application of Photodynamic Therapy with 5-Aminolevulinic Acid to Extracorporeal Photopheresis in the Treatment of Cutaneous T-Cell Lymphoma: A First-in-Human Phase I/II Study
Authors: Christensen Eidi , Foss Olav Andreas , Holien Toril , Juzenas Petras , Peng Qian
Published: June 2024

Extracorporeal photopheresis (ECP) is a therapeutic modality used for T-cell-mediated disorders. This approach involves exposing isolated white blood cells to photoactivatable 8-methoxypsoralen (8-MOP) and UVA light, aiming to induce apoptosis in T-cells and thereby modulate immune responses. However, conventional 8-MOP-ECP lacks cell selectivity, killing both healthy and diseased cells, and has shown limited treatment efficacy. An alternative approach under investigation involves the use of 5-aminolevulinic acid (ALA) in conjunction with light, referred to as ALA-based photodynamic therapy. Our previous ex vivo studies suggest that ALA-ECP exhibits greater selectivity and efficiency in killing T-cells derived from patients with T-cell-mediated disorders compared to those treated with 8-MOP-ECP. We have conducted a clinical phase I–(II) study evaluating ALA-ECP safety and tolerability in cutaneous T-cell lymphoma (CTCL). Here, 20 ALA-ECP treatments were administered to one CTCL patient, revealing no significant changes in vital signs. Two adverse events were reported; both evaluated by the Internal Safety Review Committee as non-serious. In addition, five conceivable events with mainly mild symptoms took place. During the study period, a 53% reduction in skin involvement and a 50% reduction in pruritus was observed. In conclusion, the results indicate that ALA-ECP treatment is safe and well tolerated.
Progress in Topical and Transdermal Drug Delivery Research—Focus on Nanoformulations
Authors: Lunter Dominique , Klang Victoria , Eichner Adina , Savic Sanela M. , Savic Snezana , Lian Guoping , Erdő Franciska
Published: June 2024

Skin is the largest organ and a multifunctional interface between the body and its environment. It acts as a barrier against cold, heat, injuries, infections, chemicals, radiations or other exogeneous factors, and it is also known as the mirror of the soul. The skin is involved in body temperature regulation by the storage of fat and water. It is an interesting tissue in regard to the local and transdermal application of active ingredients for prevention or treatment of pathological conditions. Topical and transdermal delivery is an emerging route of drug and cosmetic administration. It is beneficial for avoiding side effects and rapid metabolism. Many pharmaceutical, technological and cosmetic innovations have been described and patented recently in the field. In this review, the main features of skin morphology and physiology are presented and are being followed by the description of classical and novel nanoparticulate dermal and transdermal drug formulations. The biophysical aspects of the penetration of drugs and cosmetics into or across the dermal barrier and their investigation in diffusion chambers, skin-on-a-chip devices, high-throughput measuring systems or with advanced analytical techniques are also shown. The current knowledge about mathematical modeling of skin penetration and the future perspectives are briefly discussed in the end, all also involving nanoparticulated systems.
Examining the Impact of the World Health Organization 2022 Guidelines on Evaluation of Biosimilars for Non-Local Comparators in Biosimilar Studies on Middle East and North Africa Member States
Authors: Strand Michael W. , Watanabe Jonathan H.
Published: June 2024

Global support and standardization of regulation for biosimilars approval owes much of its legacy to the World Health Organization (WHO), since the first guidance by the organization on the matter was released in 2009. Since then, and with over a decade of research, the 2022 revision provides opportunities for time and financial savings to pharmaceutical manufacturers aiming to prove similarity of a potential biosimilar product to some reference product, particularly by clarifying that the use of a non-local reference product as a comparator in certain studies is permissible. This declaration has important implications, particularly in the emerging biological markets of the Middle East and North Africa region, where WHO guidelines have been integral to the regulatory framework of over a dozen countries for more than a decade. This article aims to review the impact of this revision on these countries and relevant policies on non-local comparator usage. Since 2022, this revision has been adopted only in Egypt. Many North African countries are yet to adopt a first draft of the formalized guidance. This analysis revealed that, although many of these countries reference the WHO guidelines, hesitation remains in terms of sourcing comparator products outside the US or European countries. This likely translates to slow regional development and cooperation of functioning, sustainable biosimilars markets. Future studies will be necessary to evaluate the continued development of guidance within these countries and changes in comparator sourcing norms as more time is allowed for their policies to mature and adapt to new standards.
Overexpression of Wild Soybean Expansin Gene GsEXLB14 Enhanced the Tolerance of Transgenic Soybean Hairy Roots to Salt and Drought Stresses
Authors: Wang Linlin , Zhang Tong , Li Cuiting , Zhou Changjun , Liu Bing , Wu Yaokun , He Fumeng , Xu Yongqing , Li Fenglan , Feng Xu
Published: June 2024

As a type of cell-wall-relaxing protein that is widely present in plants, expansins have been shown to actively participate in the regulation of plant growth and responses to environmental stress. Wild soybeans have long existed in the wild environment and possess abundant resistance gene resources, which hold significant value for the improvement of cultivated soybean germplasm. In our previous study, we found that the wild soybean expansin gene GsEXLB14 is specifically transcribed in roots, and its transcription level significantly increases under salt and drought stress. To further identify the function of GsEXLB14, in this study, we cloned the CDS sequence of this gene. The transcription pattern of GsEXLB14 in the roots of wild soybean under salt and drought stress was analyzed by qRT-PCR. Using an Agrobacterium rhizogenes-mediated genetic transformation, we obtained soybean hairy roots overexpressing GsEXLB14. Under 150 mM NaCl- and 100 mM mannitol-simulated drought stress, the relative growth values of the number, length, and weight of transgenic soybean hairy roots were significantly higher than those of the control group. We obtained the transcriptomes of transgenic and wild-type soybean hairy roots under normal growth conditions and under salt and drought stress through RNA sequencing. A transcriptomic analysis showed that the transcription of genes encoding expansins (EXPB family), peroxidase, H+-transporting ATPase, and other genes was significantly upregulated in transgenic hairy roots under salt stress. Under drought stress, the transcription of expansin (EXPB/LB family) genes increased in transgenic hairy roots. In addition, the transcription of genes encoding peroxidases, calcium/calmodulin-dependent protein kinases, and dehydration-responsive proteins increased significantly. The results of qRT-PCR also confirmed that the transcription pattern of the above genes was consistent with the transcriptome. The differences in the transcript levels of the above genes may be the potential reason for the strong tolerance of soybean hairy roots overexpressing the GsEXLB14 gene under salt and drought stress. In conclusion, the expansin GsEXLB14 can be used as a valuable candidate gene for the molecular breeding of soybeans.
New Intrinsic Ecological Mechanisms of Leaf Nutrient Resorption in Temperate Deciduous Trees
Authors: Wang Xingchang , Guo Yanmin , Wang Qi , Pan Jun , Quan Xiankui , Gu Jiacun , Wang Chuankuan
Published: June 2024

Leaf nutrient resorption is a critical process in plant nutrient conservation during leaf senescence. However, the ecological mechanisms underlying the large variability in nitrogen (NRE) and phosphorous (PRE) resorption efficiencies among trees remain poorly understood. We conducted a comprehensive study on NRE and PRE variability using 61 tree individuals of 10 temperate broad-leaved tree species. Three potentially interrelated intrinsic ecological mechanisms (i.e., leaf senescence phenology, leaf pigments, and energy residual) were verified. We found that a delayed leaf senescence date, increased degradation of chlorophylls and carotenoids, biosynthesis of anthocyanins, and reduced nonstructural carbohydrates were all positively correlated with NRE and PRE at the individual tree level. The intrinsic factors affecting resorption efficiency were ranked in decreasing order of importance: leaf pigments > energy residual > senescence phenology. These factors explained more variability in NRE than in PRE. Our findings highlight the significance of these three ecological mechanisms in leaf nutrient resorption and have important implications for understanding how nutrient resorption responds to climate change.
Morphological Study on the Differentiation of Flower Buds and the Embryological Stages of Male and Female Floral Organs in Lespedeza davurica (Laxm.) Schindl. cv. JinNong (Fabaceae)
Authors: Tong Lirong , Wang Juan
Published: June 2024

Lespedeza davurica (Laxm.) is a leguminous plant with significant ecological benefits, but its embryonic development mechanism remains unclear. We investigated the flower bud differentiation, megaspore and microspore formation, gametophyte development, and embryo and endosperm development in L. davurica. Our aim was to elucidate the relationship between the external morphology and internal development processes of male and female floral organs during growth, as well as the reproductive factors influencing fruiting. The results indicated that although the pistil develops later than the stamen during flower bud differentiation, both organs mature synchronously before flowering. L. davurica pollen exhibits three germination grooves, a reticulate outer wall, and papillary structures on the anther surface. In vivo pollination experiments revealed abnormal spiral growth of L. davurica pollen tubes within the style and the occurrence of callus plugs, which may reduce the seed setting rate. The anther wall development follows the dicotyledonous type, with tetrads formed through microspore meiosis exhibiting both left–right symmetry and tetrahedral arrangements. L. davurica has a single ovule, and the embryo sac develops in the monosporic polygonum type. After dormancy, the zygote undergoes multiple divisions, progressing through spherical, heart-shaped, and torpedo-shaped embryo stages, culminating in a mature embryo. A mature seed comprises cotyledons, hypocotyl, embryo, radicle, and seed coat. Phylogenetic tree analysis reveals a close genetic relationship between L. davurica and other leguminous plants from the genera Lespedeza and Medicago. This study provides valuable insights into the regulation of flowering and hybrid breeding in leguminous plants and offers a new perspective on the development of floral organs and seed setting rates.
Drought Has a Greater Negative Effect on the Growth of the C3 Chenopodium quinoa Crop Halophyte than Elevated CO2 and/or High Temperature
Authors: Rakhmankulova Zulfira , Shuyskaya Elena , Prokofieva Maria , Toderich Kristina , Saidova Luizat , Lunkova Nina , Voronin Pavel
Published: June 2024

Plant growth and productivity are predicted to be affected by rising CO2 concentrations, drought and temperature stress. The C3 crop model in a changing climate is Chenopodium quinoa Willd—a protein-rich pseudohalphyte (Amaranthaceae). Morphophysiological, biochemical and molecular genetic studies were performed on quinoa grown at ambient (400 ppm, aCO2) and elevated (800 ppm, eCO2) CO2 concentrations, drought (D) and/or high temperature (eT) treatments. Among the single factors, drought caused the greatest stress response, inducing disturbances in the light and dark photosynthesis reactions (PSII, apparent photosynthesis) and increasing oxidative stress (MDA). Futhermore, compensation mechanisms played an important protective role against eT or eCO2. The disruption of the PSII function was accompanied by the activation of the expression of PGR5, a gene of PSI cyclic electron transport (CET). Wherein under these conditions, the constant Rubisco content was maintained due to an increase in its biosynthesis, which was confirmed by the activation of rbcL gene expression. In addition, the combined stress treatments D+eT and eCO2+D+eT caused the greatest negative effect, as measured by increased oxidative stress, decreased water use efficiency, and the functioning of protective mechanisms, such as photorespiration and the activity of antioxidant enzymes. Furthermore, decreased PSII efficiency and increased non-photochemical quenching (NPQ) were not accompanied by the activation of protective mechanisms involving PSI CET. In summary, results show that the greatest stress experienced by C. quinoa plants was caused by drought and the combined stresses D+eT and eCO2+D+eT. Thus, drought consistently played a decisive role, leading to increased oxidative stress and a decrease in defense mechanism effectiveness.
Associative Bacteria and Arbuscular Mycorrhizal Fungus Increase Drought Tolerance in Maize (Zea mays L.) through Morphoanatomical, Physiological, and Biochemical Changes
Authors: Tiepo Angélica Nunes , Fávaro Mateus Henrique , Amador Talita Silveira , Tavares Leonardo Fernandes , Hertel Mariana Fernandes , Calzavara Anderson Kikuchi , de Oliveira André Luiz Martinez , Oliveira Halley Caixeta , Dias-Pereira Jaqueline , de Araújo Hugo Humberto , Bianchini Edmilson , Pimenta José Antonio , Stolf-Moreira Renata
Published: June 2024

Water deficiency has been recognized as a major abiotic stress that causes losses in maize crops around the world. The maize crop is very important due to the range of products that are derived from this plant. A potential way to reduce the damages caused by water deficiency in maize crops is through the association with plant growth-promoting bacteria (PGPB) and arbuscular mycorrhizal fungi (AMF). To define the mechanisms developed by associative PGPB and AMF in maize that are involved in protection against moderate drought (MD), this study evaluated the biometrical, anatomical, biochemical, and physiological parameters of maize grown under MD and inoculated with different PGPB (Azospirillum brasilense strain Ab-V5 and Bacillus sp. strain ZK) and with AMF. The relative water content did not change in the treatments. The association with ZK increased the shoot:total ratio, total dry weight, maximum quantum yield of photosystem II, vascular cylinder thickness, and vascular cylinder area. The Ab-V5 inoculation led to an increment in root dry weight, the area of metaxylem vessel elements, and nitrate reductase activity. The AMF association did not lead to changes in the measured parameters. The results indicate that the association with PGPB is a relevant alternative to contribute to reducing losses in maize crops under drought. However, AMF is not indicated for this crop under drought.
Effects of Red and Blue Light on the Growth, Photosynthesis, and Subsequent Growth under Fluctuating Light of Cucumber Seedlings
Authors: Wang Tengqi , Sun Qiying , Zheng Yinjian , Xu Yaliang , Liu Binbin , Li Qingming
Published: June 2024

The effects of red and blue light on growth and steady-state photosynthesis have been widely studied, but there are few studies focusing on dynamic photosynthesis and the effects of LED pre-treatment on cucumber seedlings’ growth, so in this study, cucumber (Cucumis sativus L. cv. Jinyou 365) was chosen as the test material. White light (W), monochromatic red light (R), monochromatic blue light (B), and mixed red and blue lights with different red-to-blue ratios (9:1, 7:3, 5:5, 3:7, and 1:9) were set to explore the effects of red and blue light on cucumber seedlings’ growth, steady-state photosynthesis, dynamic photosynthesis, and subsequent growth under fluctuating light. The results showed that compared with R and B, mixed red and blue light was more suitable for cucumber seedlings’ growth, and the increased blue light ratios would decrease the biomass of cucumber seedlings under mixed red and blue light; cucumber seedlings under 90% red and 10% blue mixed light (9R1B) grew better than other treatments. For steady-state photosynthesis, blue light decreased the actual net photosynthetic rate but increased the maximum photosynthetic capacity by promoting stomatal development and opening; 9R1B exhibited higher actual net photosynthetic rate, but the maximum photosynthetic capacity was low. For dynamic photosynthesis, the induction rate of photosynthetic rate and stomatal conductance were also accelerated by blue light. For subsequent growth under fluctuating light, higher maximum photosynthetic capacity and photoinduction rate could not promote the growth of cucumber seedlings under subsequent fluctuating light, while seedlings pre-treated with 9R1B and B grew better under subsequent fluctuating light due to the high plant height and leaf area. Overall, cucumber seedlings treated with 9R1B exhibited the highest biomass and it grew better under subsequent fluctuating light due to the higher actual net photosynthetic rate, plant height, and leaf area.
Ascorbic Acid Improves Tomato Salt Tolerance by Regulating Ion Homeostasis and Proline Synthesis
Authors: Chen Xianjun , Han Hongwei , Cong Yundan , Li Xuezhen , Zhang Wenbo , Cui Jinxia , Xu Wei , Pang Shengqun , Liu Huiying
Published: June 2024

In this study, processing tomato (Solanum lycopersicum L.) ‘Ligeer 87-5’ was hydroponically cultivated under 100 mM NaCl to simulate salt stress. To investigate the impacts on ion homeostasis, osmotic regulation, and redox status in tomato seedlings, different endogenous levels of ascorbic acid (AsA) were established through the foliar application of 0.5 mM AsA (NA treatment), 0.25 mM lycorine (LYC, an inhibitor of AsA synthesis; NL treatment), and a combination of LYC and AsA (NLA treatment). The results demonstrated that exogenous AsA significantly increased the activities and gene expressions of key enzymes (L-galactono-1,4-lactone dehydrogenase (GalLDH) and L-galactose dehydrogenase (GalDH)) involved in AsA synthesis in tomato seedling leaves under NaCl stress and NL treatment, thereby increasing cellular AsA content to maintain its redox status in a reduced state. Additionally, exogenous AsA regulated multiple ion transporters via the SOS pathway and increased the selective absorption of K+, Ca2+, and Mg2+ in the aerial parts, reconstructing ion homeostasis in cells, thereby alleviating ion imbalance caused by salt stress. Exogenous AsA also increased proline dehydrogenase (ProDH) activity and gene expression, while inhibiting the activity and transcription levels of Δ1-pyrroline-5-carboxylate synthetase (P5CS) and ornithine-δ-aminotransferase (OAT), thereby reducing excessive proline content in the leaves and alleviating osmotic stress. LYC exacerbated ion imbalance and osmotic stress caused by salt stress, which could be significantly reversed by AsA application. Therefore, exogenous AsA application increased endogenous AsA levels, reestablished ion homeostasis, maintained osmotic balance, effectively alleviated the inhibitory effect of salt stress on tomato seedling growth, and enhanced their salt tolerance.