bluuebunny/crossref_metadata_2025 huggingface dataset:
The Classification, Molecular Structure and Biological Biosynthesis of Flavonoids, and Their Roles in Biotic and Abiotic Stresses
Authors: Zhuang Wei-Bing , Li Yu-Hang , Shu Xiao-Chun , Pu Yu-Ting , Wang Xiao-Jing , Wang Tao , Wang Zhong
Published: April 2023

With the climate constantly changing, plants suffer more frequently from various abiotic and biotic stresses. However, they have evolved biosynthetic machinery to survive in stressful environmental conditions. Flavonoids are involved in a variety of biological activities in plants, which can protect plants from different biotic (plant-parasitic nematodes, fungi and bacteria) and abiotic stresses (salt stress, drought stress, UV, higher and lower temperatures). Flavonoids contain several subgroups, including anthocyanidins, flavonols, flavones, flavanols, flavanones, chalcones, dihydrochalcones and dihydroflavonols, which are widely distributed in various plants. As the pathway of flavonoid biosynthesis has been well studied, many researchers have applied transgenic technologies in order to explore the molecular mechanism of genes associated with flavonoid biosynthesis; as such, many transgenic plants have shown a higher stress tolerance through the regulation of flavonoid content. In the present review, the classification, molecular structure and biological biosynthesis of flavonoids were summarized, and the roles of flavonoids under various forms of biotic and abiotic stress in plants were also included. In addition, the effect of applying genes associated with flavonoid biosynthesis on the enhancement of plant tolerance under various biotic and abiotic stresses was also discussed.
Multiple Strategies to Develop Small Molecular KRAS Directly Bound Inhibitors
Authors: Zhou Xile , Ji Yang , Zhou Jinming
Published: April 2023

KRAS gene mutation is widespread in tumors and plays an important role in various malignancies. Targeting KRAS mutations is regarded as the “holy grail” of targeted cancer therapies. Recently, multiple strategies, including covalent binding strategy, targeted protein degradation strategy, targeting protein and protein interaction strategy, salt bridge strategy, and multivalent strategy, have been adopted to develop KRAS direct inhibitors for anti-cancer therapy. Various KRAS-directed inhibitors have been developed, including the FDA-approved drugs sotorasib and adagrasib, KRAS-G12D inhibitor MRTX1133, and KRAS-G12V inhibitor JAB-23000, etc. The different strategies greatly promote the development of KRAS inhibitors. Herein, the strategies are summarized, which would shed light on the drug discovery for both KRAS and other “undruggable” targets.
Isomers of the Tomato Glycoalkaloids α-Tomatine and Dehydrotomatine: Relationship to Health Benefits
Authors: Kozukue Nobuyuki , Kim Dong-Seok , Choi Suk-Hyun , Mizuno Masashi , Friedman Mendel
Published: April 2023

High-performance liquid chromatography (HPLC) analysis of three commercial tomatine samples and another isolated from green tomatoes revealed the presence of two small peaks in addition to those associated with the glycoalkaloids dehydrotomatine and α-tomatine. The present study investigated the possible structures of the compounds associated with the two small peaks using HPLC–mass spectrophotometric (MS) methods. Although the two peaks elute much earlier on chromatographic columns than the elution times of the known tomato glycoalkaloids dehydrotomatine and α-tomatine, isolation of the two compounds by preparative chromatography and subsequent analysis by MS shows the two compounds have identical molecular weights, tetrasaccharide side chains, and MS and MS/MS fragmentation patterns to dehydrotomatine and α-tomatine. We suggest the two isolated compounds are isomeric forms of dehydrotomatine and α-tomatine. The analytical data indicate that widely used commercial tomatine preparations and those extracted from green tomatoes and tomato leaves consist of a mixture of α-tomatine, dehydrotomatine, an α-tomatine isomer, and a dehydrotomatine isomer in an approximate ratio of 81:15:4:1, respectively. The significance of the reported health benefits of tomatine and tomatidine is mentioned.
Multidimensional Chromatographic Fingerprinting Combined with Chemometrics for the Identification of Regulated Plants in Suspicious Plant Food Supplements
Authors: Ranjan Surbhi , Adams Erwin , Deconinck Eric
Published: April 2023

The popularity of plant food supplements has seen explosive growth all over the world, making them susceptible to adulteration and fraud. This necessitates a screening approach for the detection of regulated plants in plant food supplements, which are usually composed of complex plant mixtures, thus making the approach not so straightforward. This paper aims to tackle this problem by developing a multidimensional chromatographic fingerprinting method aided by chemometrics. To render more specificity to the chromatogram, a multidimensional fingerprint (absorbance × wavelength × retention time) was considered. This was achieved by selecting several wavelengths through a correlation analysis. The data were recorded using ultra-high-performance liquid chromatography (UHPLC) coupled with diode array detection (DAD). Chemometric modelling was performed by partial least squares–discriminant analysis (PLS-DA) through (a) binary modelling and (b) multiclass modelling. The correct classification rates (ccr%) by cross-validation, modelling, and external test set validation were satisfactory for both approaches, but upon further comparison, binary models were preferred. As a proof of concept, the models were applied to twelve samples for the detection of four regulated plants. Overall, it was revealed that the combination of multidimensional fingerprinting data with chemometrics was feasible for the identification of regulated plants in complex botanical matrices.
Preparation of Multifunctional Surfactants Derived from Sodium Dodecylbenzene Sulfonate and Their Use in Oil-Field Chemistry
Authors: Li Yongfei , Bai Quanzheng , Li Qiang , Huang Hai , Ni Weijun , Wang Qian , Xin Xin , Zhao Bin , Chen Gang
Published: April 2023

Four products were obtained from sodium dodecylbenzene sulfonate (SDBS) and formaldehyde (40% solution) using a simple reaction. The products were characterized by TGA, IR, UV and MS to confirm the major chemicals in each sample. The new products could reduce the interfacial tension between oil and water in the experimental temperature range further compared to SDBS. The emulsion ability was also enhanced by SDBS-1 to SDBS-4. The oil-displacement efficiencies of SDBS-1 to SDBS-4 were obviously higher than that of SDBS, and the oil-displacement efficiency of SDBS-2 was the best, with an efficiency of 25%. The experimental results all indicate that these products have an excellent ability to reduce oil–water interfacial tension and that they can be used in the oil and petrochemical industry for oil production and have certain practical uses.
Fano Resonance in Near-Field Thermal Radiation of Two-Dimensional Van der Waals Heterostructures
Authors: Wu Huihai , Liu Xiaochuan , Zhu Keyong , Huang Yong
Published: April 2023

Two-dimensional (2D) materials and their vertically stacked heterostructures have attracted much attention due to their novel optical properties and strong light-matter interactions in the infrared. Here, we present a theoretical study of the near-field thermal radiation of 2D vdW heterostructures vertically stacked of graphene and monolayer polar material (2D hBN as an example). An asymmetric Fano line shape is observed in its near-field thermal radiation spectrum, which is attributed to the interference between the narrowband discrete state (the phonon polaritons in 2D hBN) and a broadband continuum state (the plasmons in graphene), as verified by the coupled oscillator model. In addition, we show that 2D van der Waals heterostructures can achieve nearly the same high radiative heat flux as graphene but with markedly different spectral distributions, especially at high chemical potentials. By tuning the chemical potential of graphene, we can actively control the radiative heat flux of 2D van der Waals heterostructures and manipulate the radiative spectrum, such as the transition from Fano resonance to electromagnetic-induced transparency (EIT). Our results reveal the rich physics and demonstrate the potential of 2D vdW heterostructures for applications in nanoscale thermal management and energy conversion.
Editorial for Special Issue “Plasmon Assisted Near-Field Manipulation and Photocatalysis”
Authors: Zhang Zhenglong
Published: April 2023

Accurately establishing the near field is crucial to enhancing optical manipulation and resolution, and is pivotal to the application of nanoparticles in the field of photocatalysis [...]
Nanoporous Amorphous Carbon with Exceptional Ultra-High Strength
Authors: Castillo-Castro Daniel , Correa Felipe , Aparicio Emiliano , Amigo Nicolás , Prada Alejandro , Figueroa Juan , González Rafael I. , Bringa Eduardo , Valencia Felipe J.
Published: April 2023

Nanoporous materials show a promising combination of mechanical properties in terms of their relative density; while there are numerous studies based on metallic nanoporous materials, here we focus on amorphous carbon with a bicontinuous nanoporous structure as an alternative to control the mechanical properties for the function of filament composition.Using atomistic simulations, we study the mechanical response of nanoporous amorphous carbon with 50% porosity, with sp3 content ranging from 10% to 50%. Our results show an unusually high strength between 10 and 20 GPa as a function of the %sp3 content. We present an analytical analysis derived from the Gibson–Ashby model for porous solids, and from the He and Thorpe theory for covalent solids to describe Young’s modulus and yield strength scaling laws extremely well, revealing also that the high strength is mainly due to the presence of sp3 bonding. Alternatively, we also find two distinct fracture modes: for low %sp3 samples, we observe a ductile-type behavior, while high %sp3 leads to brittle-type behavior due to high high shear strain clusters driving the carbon bond breaking that finally promotes the filament fracture. All in all, nanoporous amorphous carbon with bicontinuous structure is presented as a lightweight material with a tunable elasto-plastic response in terms of porosity and sp3 bonding, resulting in a material with a broad range of possible combinations of mechanical properties.
The Hydrogenation of Crotonaldehyde on PdCu Single Atom Alloy Catalysts
Authors: Islam Mohammed J. , Granollers Mesa Marta , Osatiashtiani Amin , Taylor Martin J. , Isaacs Mark A. , Kyriakou Georgios
Published: April 2023

Recyclable PdCu single atom alloys supported on Al2O3 were applied to the selective hydrogenation of crotonaldehyde to elucidate the minimum number of Pd atoms required to facilitate the sustainable transformation of an α,β-unsaturated carbonyl molecule. It was found that, by diluting the Pd content of the alloy, the reaction activity of Cu nanoparticles can be accelerated, enabling more time for the cascade conversion of butanal to butanol. In addition, a significant increase in the conversion rate was observed, compared to bulk Cu/Al2O3 and Pd/Al2O3 catalysts when normalising for Cu and Pd content, respectively. The reaction selectivity over the single atom alloy catalysts was found to be primarily controlled by the Cu host surface, mainly leading to the formation of butanal but at a significantly higher rate than the monometallic Cu catalyst. Low quantities of crotyl alcohol were observed over all Cu-based catalysts but not for the Pd monometallic catalyst, suggesting that it may be a transient species converted immediately to butanol and or isomerized to butanal. These results demonstrate that fine-tuning the dilution of PdCu single atom alloy catalysts can leverage the activity and selectivity enhancement, and lead to cost-effective, sustainable, and atom-efficient alternatives to monometallic catalysts.
Effect of Rotavirus Infection and 2′-Fucosyllactose Administration on Rat Intestinal Gene Expression
Authors: Sáez-Fuertes Laura , Azagra-Boronat Ignasi , Massot-Cladera Malén , Knipping Karen , Garssen Johan , Franch Àngels , Castell Margarida , Pérez-Cano Francisco J. , Rodríguez-Lagunas María J.
Published: April 2023

Viral infections are described as modifying host gene expression; however, there is limited insight regarding rotavirus (RV) infections. This study aimed to assess the changes in intestinal gene expression after RV infection in a preclinical model, and the effect of 2-fucosyllactose (2′-FL) on this process. From days 2 to 8 of life, rats were supplemented with the dietary oligosaccharide 2′-FL or vehicle. In addition, an RV was inoculated on day 5 to nonsupplemented animals (RV group) and to 2′-FL-fed animals (RV+2′-FL group). Incidence and severity of diarrhea were established. A portion from the middle part of the small intestine was excised for gene expression analysis by microarray kit and qPCR. In nonsupplemented animals, RV-induced diarrhea upregulated host antiviral genes (e.g., Oas1a, Irf7, Ifi44, Isg15) and downregulated several genes involved in absorptive processes and intestinal maturation (e.g., Onecut2, and Ccl19). The 2′-FL-supplemented and infected animals had less diarrhea; however, their gene expression was affected in a similar way as the control-infected animals, with the exception of some immunity/maturation markers that were differentially expressed (e.g., Ccl12 and Afp). Overall, assessing the expression of these key genes may be useful in the evaluation of the efficacy of nutritional interventions or treatments for RV infection.
Comment on Hack et al. Effect of Guarana (Paullinia cupana) on Cognitive Performance: A Systematic Review and Meta-Analysis. Nutrients 2023, 15, 434
Authors: Gurney Tom , Ronca Flaminia
Published: April 2023

We have read the recent systematic review and meta-analysis by Hack et al. [...]
Reply to Gurney, T.; Ronca, F. Comment on “Hack et al. Effect of Guarana (Paullinia cupana) on Cognitive Performance: A Systematic Review and Meta-Analysis. Nutrients 2023, 15, 434”
Authors: Hack Brian , Penna Eduardo Macedo , Talik Tyler , Chandrashekhar Rohan , Millard-Stafford Mindy
Published: April 2023

We thank Dr. Gurney for his interest and comment [...]
Low-Carbohydrate Diet and Human Health
Authors: Papadopoulou Sousana K. , Nikolaidis Pantelis T.
Published: April 2023

Low-carbohydrate diets were initially recommended as a therapeutic dietary scheme for epilepsy, while increasing evidence suggests their potential application in the management of several other pathologies, such as diabetes, neoplasms, gastrointestinal and lung diseases, diseases of the cardiovascular system, as well as obesity [...]
Limosilactobacillus fermentum MG4294 and Lactiplantibacillus plantarum MG5289 Ameliorates Nonalcoholic Fatty Liver Disease in High-Fat Diet-Induced Mice
Authors: Lee Ji Yeon , An Minju , Heo Huijin , Park Jeong-Yong , Lee Junsoo , Kang Chang-Ho
Published: April 2023

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease and the leading cause of liver-related deaths worldwide. It has been established that microorganisms are involved in the interaction between the intestinal lumen and the liver; therefore, studies on probiotics as potential candidates are increasing. This study evaluated the effects of Limosilactobacillus fermentum MG4294 and Lactiplantibacillus plantarum MG5289 on NAFLD. The MG4294 and MG5289 reduced lipid accumulation in FFA-induced HepG2 by suppressing the adipogenic proteins through the regulation of AMP-activated protein kinase (AMPK). The administration of these strains in the HFD-induced mice model lowered body weight, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and cholesterol levels. In particular, MG4294 and MG5289 restored liver TG and TC to normal levels by lowering lipid and cholesterol-related proteins via the modulation of AMPK in the liver tissue. In addition, the administration of MG4294 and MG5289 reduced pro-inflammatory cytokines (tumor necrosis factor (TNF)-α and interleukin (IL)-1β-, and IL6) in the intestinal tissues of the HFD-induced mouse model. In conclusion, MG4294 and MG5289 can be presented as probiotics with the potential to prevent NAFLD.
The Potential of DHA as Cancer Therapy Strategies: A Narrative Review of In Vitro Cytotoxicity Trials
Authors: de Freitas Rodrigues Jaqueline , Philippsen Hellen Kempfer , Dolabela Maria Fani , Nagamachi Cleusa Yoshiko , Pieczarka Julio Cesar
Published: April 2023

Docosahexaenoic acid (DHA), also known as omega-3 (n-3) polyunsaturated fatty acid (PUFA), is a natural compound that has demonstrated pharmacological activity against several malignant neoplasms. Available cancer treatments cause side effects, affect healthy cells, reduce the quality of life of patients and may cause resistance to antineoplastics. For these reasons, the search for new therapies is continuous. This narrative review aimed to compile information on in vitro experiments that study the cytotoxic effect of DHA or molecules derived from DHA in tumor and nontumor cells. This was performed to highlight the potential of DHA as a strategy for cancer therapy and to gather information, which will help researchers plan experimental designs and develop research to discover effective therapies against cancer. In addition, studies were presented that demonstrate the dose of DHA that can treat patients with cancer. Thus, a search was conducted for articles on the SCOPUS and Web of Science platforms, published until 2022, that analyzed the action of DHA against breast, lung, colorectal, prostate, stomach and liver cancers. Cytotoxic effects were observed in tumor and nontumor cell lines, and these results varied with the type of cell line studied, drug concentration, incubation time and treatment combination, i.e., with DHA alone, combined with other drugs and with molecules derived from DHA. In patients with cancer, in all analyzed studies, DHA intake was associated with eicosapentaenoic acid (EPA) and/or proteins to aid chemotherapy, and with this procedure, tumor reduction, chemotherapy tolerance and muscle mass gain were obtained. This work contributes to the community by demonstrating the possible applicability of DHA in the pharmaceutical area of oncological therapies.
Neuroprotective Effects of Ecklonia cava in a Chronic Neuroinflammatory Disease Model
Authors: Jo Seong-Lae , Yang Hyun , Jeong Kang-Joo , Lee Hye-Won , Hong Eui-Ju
Published: April 2023

Inflammation is a natural defense mechanism against noxious stimuli, but chronic inflammation can lead to various chronic diseases. Neuroinflammation in the central nervous system plays an important role in the development and progression of neurodegenerative diseases. Polyphenol-rich natural products, such as Ecklonia cava (E. cava), are known to have anti-inflammatory and antioxidant properties and can provide treatment strategies for neurodegenerative diseases by controlling neuroinflammation. We investigated the effects of an E. cava extract on neuroinflammation and neurodegeneration under chronic inflammatory conditions. Mice were pretreated with E. cava extract for 19 days and then exposed to E. cava with lipopolysaccharide (LPS) for 1 week. We monitored pro-inflammatory cytokines levels in the serum, inflammation-related markers, and neurodegenerative markers using Western blotting and qRT-PCR in the mouse cerebrum and hippocampus. E. cava reduced pro-inflammatory cytokine levels in the blood and brain of mice with LPS-induced chronic inflammation. We also measured the activity of genes related to neuroinflammation and neurodegeneration. Surprisingly, E. cava decreased the activity of markers associated with inflammation (NF-kB and STAT3) and a neurodegenerative disease marker (glial fibrillary acidic protein, beta-amyloid) in the cerebrum and hippocampus of mice. We suggest that E. cava extract has the potential as a protective agent against neuroinflammation and neurodegenerative diseases.
Maternal Serum Vitamin B12 during Pregnancy and Offspring Autism Spectrum Disorder
Authors: Sourander Andre , Silwal Sanju , Surcel Heljä-Marja , Hinkka-Yli-Salomäki Susanna , Upadhyaya Subina , McKeague Ian W. , Cheslack-Postava Keely , Brown Alan S.
Published: April 2023

This study examined the association between maternal serum vitamin B12 levels during early pregnancy and offspring autism spectrum disorders (ASD) and subtypes. Based on a Finnish national birth cohort, case offspring (n = 1558) born in 1987–2007 and diagnosed with ASD by 2015 were matched with one control on date of birth, sex and place of birth. Maternal vitamin B12 levels were measured during first and early second trimesters of pregnancy. High maternal vitamin B12 levels (≥81th percentile) was associated with increased risk for offspring childhood autism, adjusted odds ratio, 1.59, 95% confidence interval 1.06–2.41 (p = 0.026). No significant associations were observed between maternal vitamin B12 levels and offspring Asperger’s or pervasive developmental disorder/NOS.
Complementary Feeding Practices and Childhood Malnutrition in South Africa: The Potential of Moringa Oleifera Leaf Powder as a Fortificant: A Narrative Review
Authors: Sokhela Hlengiwe , Govender Laurencia , Siwela Muthulisi
Published: April 2023

Poor complementary feeding is a common practice in developing regions, including South Africa (SA), and is one of the main contributing factors to childhood malnutrition. This paper reviews the literature on complementary feeding practices in SA and the potential of fortifying home-prepared complementary foods with Moringa oleifera to improve their nutritional composition. Studies that investigated complementary feeding practices, indigenous crops, nutritional benefits of Moringa oleifera, and the use of MOLP as a fortificant both locally and globally were included in this review. In SA, maize meal and commercial cereal are the most commonly used complementary infant foods. The diet consumed by children from vulnerable households commonly has insufficient nutrients. Foods consumed are generally high in starch and low in other essential nutrients, including good-quality protein. Impoverished individuals consume poor-quality foods as they are unable to afford a diversified diet with food from different food groups, such as protein, fruits, and vegetables. In SA, various programs have been implemented to reduce the incidence of childhood malnutrition. However, childhood malnutrition remains on the rise. This shows a need for complementary food-based strategies that can be implemented and sustained at a household level. This can be conducted through the use of accessible indigenous crops such as Moringa oleifera. Moringa oleifera contains essential nutrients such as proteins, amino acids, vitamins, and minerals. Therefore, it could possibly be used as a home-prepared complementary food fortificant to enhance nutritional composition. Before complementary foods can be fortified with Moringa oleifera, popular home-prepared complementary foods must be identified.
Formula Milk Supplementation and Bone Acquisition in 4–6 Years Chinese Children: A 12-Month Cluster-Randomized Controlled Trial
Authors: Li Bang-Yan , Mahe Jin-Li , Hao Jing-Yu , Ye Wen-Hui , Bai Xue-Fei , Feng Hao-Tian , Szeto Ignatius Man-Yau , Jing Li-Peng , Zhao Zi-Fu , Chen Yu-Ming
Published: April 2023

Dairy foods are crucial for adequate calcium intake in young children, but scarce data are available on the effects of formula milk on bone acquisition. This cluster-randomized controlled trial investigated the effects of the supplementation of formula milk on bone health in rural children accustomed to a low-calcium diet between September 2021 and September 2022. We recruited 196 healthy children aged 4–6 years from two kindergartens in Huining County, Northwest China. A class-based randomization was used to assign them to receive 60 g of formula milk powder containing 720 mg calcium and 4.5 µg vitamin D or 20–30 g of bread per day for 12 months, respectively. Bone mineral density (BMD) and bone mineral content (BMC) at the left forearm and calcaneus, bone biomarkers, bone-related hormones/growth factors, and body measures were determined at baseline, 6, and 12 months. A total of 174 children completed the trial and were included in the analysis. Compared with the control group, formula milk intervention showed significant extra increments in BMD (3.77% and 6.66%) and BMC (4.55% and 5.76%) at the left forearm at 6th and 12th months post-intervention (all p < 0.001), respectively. Similar trends were observed in BMD (2.83%) and BMC (2.38%) in the left calcaneus at 6 months (p < 0.05). The milk intervention (vs. control) also showed significant changes in the serum concentrations of osteocalcin level (−7.59%, p = 0.012), 25-hydroxy-vitamin-D (+5.54%, p = 0.001), parathyroid hormone concentration (−15.22%, p = 0.003), and insulin-like growth factor 1 (+8.36%, p = 0.014). The percentage increases in height were 0.34%, 0.45%, and 0.42% higher in the milk group than in the control group after 3-, 6-, and 9-month intervention, respectively (p < 0.05). In summary, formula milk supplementation enhances bone acquisition at the left forearm in young Chinese children.
A Phase 2a, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of ALS-L1023 in Non-Alcoholic Fatty Liver Disease
Authors: Kim Gi-Ae , Cho Hyun Chin , Jeong Soung Won , Kang Bo-Kyeong , Kim Mimi , Jung Seungwon , Hwang Jungwook , Yoon Eileen L. , Jun Dae Won
Published: April 2023

Preclinical data have shown that the herbal extract, ALS-L1023, from Melissa officinalis reduces visceral fat and hepatic steatosis. We aimed to assess the safety and efficacy of ALS-L1023 as the treatment of non-alcoholic fatty liver disease (NAFLD). We conducted a 24-week randomized, double-blind, placebo-controlled 2a study in patients with NAFLD (MRI-proton density fat fraction [MRI-PDFF] ≥ 8% and liver fibrosis ≥ 2.5 kPa on MR elastography [MRE]) in Korea. Patients were randomly assigned to 1800 mg ALS-L1023 (n = 19), 1200 mg ALS-L1023 (n = 21), or placebo (n = 17) groups. Efficacy endpoints included changes in liver fat on MRI-PDFF, liver stiffness on MRE, and liver enzymes. For the full analysis set, a relative hepatic fat reduction from baseline was significant in the 1800 mg ALS-L1023 group (−15.0%, p = 0.03). There was a significant reduction in liver stiffness from baseline in the 1200 mg ALS-L1023 group (−10.7%, p = 0.03). Serum alanine aminotransferase decreased by −12.4% in the 1800 mg ALS-L1023 group, −29.8% in the 1200 mg ALS-L1023 group, and −4.9% in the placebo group. ALS-L1023 was well tolerated and there were no differences in the incidence of adverse events among the study groups. ALS-L1023 could reduce hepatic fat content in patients with NAFLD.
rAAV2-Mediated Restoration of GALC in Neural Stem Cells from Krabbe Patient-Derived iPSCs
Authors: Tian Guoshuai , Cao Chunyu , Li Shuyue , Wang Wei , Zhang Ye , Lv Yafeng
Published: April 2023

Krabbe disease is a rare neurodegenerative fatal disease. It is caused by deficiency of the lysosomal enzyme galactocerebrosidase (GALC), which results in progressive accumulation of galactolipid substrates in myelin-forming cells. However, there is still a lack of appropriate neural models and effective approaches for Krabbe disease. We generated induced pluripotent stem cells (iPSCs) from a Krabbe patient previously. Here, Krabbe patient-derived neural stem cells (K-NSCs) were induced from these iPSCs. By using nine kinds of recombinant adeno-associated virus (rAAV) vectors to infect K-NSCs, we found that the rAAV2 vector has high transduction efficiency for K-NSCs. Most importantly, rAAV2-GALC rescued GALC enzymatic activity in K-NSCs. Our findings not only establish a novel patient NSC model for Krabbe disease, but also firstly indicate the potential of rAAV2-mediated gene therapy for this devastating disease.
Clinical Confirmation of Pan-Amyloid Reactivity of Radioiodinated Peptide 124I-p5+14 (AT-01) in Patients with Diverse Types of Systemic Amyloidosis Demonstrated by PET/CT Imaging
Authors: Martin Emily B. , Stuckey Alan , Powell Dustin , Lands Ronald , Whittle Bryan , Wooliver Craig , Macy Sallie , Foster James S. , Guthrie Spencer , Kennel Stephen J. , Wall Jonathan S.
Published: April 2023

There are at least 20 distinct types of systemic amyloidosis, all of which result in the organ-compromising accumulation of extracellular amyloid deposits. Amyloidosis is challenging to diagnose due to the heterogeneity of the clinical presentation, yet early detection is critical for favorable patient outcomes. The ability to non-invasively and quantitatively detect amyloid throughout the body, even in at-risk populations, before clinical manifestation would be invaluable. To this end, a pan-amyloid-reactive peptide, p5+14, has been developed that is capable of binding all types of amyloid. Herein, we demonstrate the ex vivo pan-amyloid reactivity of p5+14 by using peptide histochemistry on animal and human tissue sections containing various types of amyloid. Furthermore, we present clinical evidence of pan-amyloid binding using iodine-124-labeled p5+14 in a cohort of patients with eight (n = 8) different types of systemic amyloidosis. These patients underwent PET/CT imaging as part of the first-in-human Phase 1/2 clinical trial evaluating this radiotracer (NCT03678259). The uptake of 124I-p5+14 was observed in abdominothoracic organs in patients with all types of amyloidosis evaluated and was consistent with the disease distribution described in the medical record and literature reports. On the other hand, the distribution in healthy subjects was consistent with radiotracer catabolism and clearance. The early and accurate diagnosis of amyloidosis remains challenging. These data support the utility of 124I-p5+14 for the diagnosis of varied types of systemic amyloidosis by PET/CT imaging.
Imageable AuNP-ECM Hydrogel Tissue Implants for Regenerative Medicine
Authors: Shilo Malka , Baruch Ester-Sapir , Wertheim Lior , Oved Hadas , Shapira Assaf , Dvir Tal
Published: April 2023

In myocardial infarction, a blockage in one of the coronary arteries leads to ischemic conditions in the left ventricle of the myocardium and, therefore, to significant death of contractile cardiac cells. This process leads to the formation of scar tissue, which reduces heart functionality. Cardiac tissue engineering is an interdisciplinary technology that treats the injured myocardium and improves its functionality. However, in many cases, mainly when employing injectable hydrogels, the treatment may be partial because it does not fully cover the diseased area and, therefore, may not be effective and even cause conduction disorders. Here, we report a hybrid nanocomposite material composed of gold nanoparticles and an extracellular matrix-based hydrogel. Such a hybrid hydrogel could support cardiac cell growth and promote cardiac tissue assembly. After injection of the hybrid material into the diseased area of the heart, it could be efficiently imaged by magnetic resonance imaging (MRI). Furthermore, as the scar tissue could also be detected by MRI, a distinction between the diseased area and the treatment could be made, providing information about the ability of the hydrogel to cover the scar. We envision that such a nanocomposite hydrogel may improve the accuracy of tissue engineering treatment.
Poly(l-Ornithine)-Based Polymeric Micelles as pH-Responsive Macromolecular Anticancer Agents
Authors: Pan Miao , Lu Chao , Zhang Wancong , Huang Huan , Shi Xingyu , Tang Shijie , Liu Daojun
Published: April 2023

Anticancer peptides and polymers represent an emerging field of tumor treatment and can physically interact with tumor cells to address the problem of multidrug resistance. In the present study, poly(l-ornithine)-b-poly(l-phenylalanine) (PLO-b-PLF) block copolypeptides were prepared and evaluated as macromolecular anticancer agents. Amphiphilic PLO-b-PLF self-assembles into nanosized polymeric micelles in aqueous solution. Cationic PLO-b-PLF micelles interact steadily with the negatively charged surfaces of cancer cells via electrostatic interactions and kill the cancer cells via membrane lysis. To alleviate the cytotoxicity of PLO-b-PLF, 1,2-dicarboxylic-cyclohexene anhydride (DCA) was anchored to the side chains of PLO via an acid-labile β-amide bond to fabricate PLO(DCA)-b-PLF. Anionic PLO(DCA)-b-PLF showed negligible hemolysis and cytotoxicity under neutral physiological conditions but recovered cytotoxicity (anticancer activity) upon charge reversal in the weakly acidic microenvironment of the tumor. PLO-based polypeptides might have potential applications in the emerging field of drug-free tumor treatment.
Linker-Free Synthesis of Antimicrobial Peptides Using a Novel Cleavage Reagent: Characterisation of the Molecular and Ionic Composition by nanoESI-HR MS
Authors: Segovia Roser , Díaz-Lobo Mireia , Cajal Yolanda , Vilaseca Marta , Rabanal Francesc
Published: April 2023

The efficient preparation of novel bioactive peptide drugs requires the availability of reliable and accessible chemical methodologies together with suitable analytical techniques for the full characterisation of the synthesised compounds. Herein, we describe a novel acidolytic method with application to the synthesis of cyclic and linear peptides involving benzyl-type protection. The process consists of the in situ generation of anhydrous hydrogen bromide and a trialkylsilyl bromide that acts as protic and Lewis acid reagents. This method proved to be useful to effectively remove benzyl-type protecting groups and cleave Fmoc/tBu assembled peptides directly attached to 4-methylbenzhydrylamine (MBHA) resins with no need for using mild trifluoroacetic acid labile linkers. The novel methodology was successful in synthesising three antimicrobial peptides, including the cyclic compound polymyxin B3, dusquetide, and RR4 heptapeptide. Furthermore, electrospray mass spectrometry (ESI-MS) is successfully used for the full characterisation of both the molecular and ionic composition of the synthetic peptides.
Significant Substrate Effects on Electromagnetic Scattering by Particles in the Infrared Atmospheric Window
Authors: Gao Feifei , Zhang Shangyu , Zhang Wenjie , Ma Lanxin , Liu Linhua
Published: April 2023

Particle-dispersed coatings emerged as a promising approach to regulate the apparent radiative properties of underlying substrates in various applications, including but not limited to radiative cooling, thermal management, and infrared stealth. However, most research efforts in this field overlooked the dependent scattering mechanisms between the particles and the substrate, which can impact the optical properties of the particles. In this study, we explored the particle-substrate interactions within the atmospheric radiative window of 8–14 µm. Using the T-matrix method, we calculated the scattering and absorption efficiencies of a dielectric/metallic particle situated above a metallic/dielectric substrate, considering the different gap sizes. Near the small gaps (<0.5a with a the sphere radius), we found that the strong local fields induced by the interaction between the induced and image charges largely enhanced the absorption and scattering efficiencies of the particles. With the increasing gap sizes, the absorption and scattering efficiencies presented a significant oscillation with a period of about 4.5a, which was attributed to the interference (standing wave) between the scattered fields from the sphere and the reflected fields from the substrate. Our findings identify a crucial role of the particle–substrate interactions in the infrared properties of particles, which may guide a comprehensive insight on the apparent radiative properties of the particle composite coatings.
A Theoretical Study on Mid-Infrared Difference Frequency Generation Based on Periodically Poled Thin-Film LiNbO3
Authors: Jia Runze , Liu Meihong , Liu Jiamin , Hua Pingrang , Zhang Delong
Published: April 2023

A mid-infrared difference frequency generator (DFG) based on a periodically poled thin-film lithium niobate rib waveguide on a sapphire substrate is theoretically studied. A mode analysis is carried out at the mid-infrared region, and the analysis focuses on the effects of waveguide geometry on effective refractive indices of a few lower-order modes. A complete theory suitable for modeling a DFG based on a waveguide structure is described. Its validity is confirmed by comparing the theoretical results with previously reported experimental data. Explicit expressions are presented for nonlinear conversion efficiency, thermal tunability and quasi-phase matching (QPM) bandwidth. The effects of waveguide geometry and mode hybridization on the effective mode field area and mode overlap factor, which are either inversely or linearly proportional to nonlinear conversion efficiency, are studied in detail. In this article, an optimized mid-infrared DFG with improved geometry that exhibits excellent performance, including a higher nonlinear conversion efficiency of 230–273% W−1cm−2 in the temperature range of 20–120 °C; a larger temperature tunability of 2.2 nm/°C; a larger QPM bandwidth of ~130 nm; and a higher idler wave output power, as much as −2 dBm when Pp = 20 dBm and Ps = 11.5 dBm, is suggested.
Maintenance of Methyl-Esterified Pectin Level in Pollen Mother-Cell Stages Is Required for Microspore Development
Authors: Hasegawa Kazuya , Ichikawa Ai , Takeuchi Haruki , Nakamura Atsuko , Iwai Hiroaki
Published: April 2023

Pectin modification and degradation are vital for plant development, although the underlying mechanisms are still not well understood. Furthermore, reports on the function of pectin in early pollen development are limited. We generated OsPME-FOX rice lines with little methyl-esterified pectin even in the early-pollen mother-cell stage due to overexpression of the gene encoding pectin-methylesterase. Overexpression of OsPME1 in rice increased the activity of PME, which decreased the degree of pectin methyl esterification in the cell wall. OsPME1-FOX grew normally and showed abnormal phenotypes in anther and pollen development, especially in terms of the pollen mother-cell stage. In addition, we examined modifications of cell-wall polysaccharides at the cellular level using antibodies against polysaccharides. Immunohistochemical staining using LM19 and LM20 showed that methyl-esterified pectin distribution and the pectin contents in pollen mother-cell wall decreased in OsPME1-FOX compared with the wild type. Thus, the maintenance of methyl-esterified pectin plays a role in degrading and maintaining the pollen mother-cell wall during microspore development.
The Impact of Heavy Metal Accumulation on Some Physiological Parameters in Silphium perfoliatum L. Plants Grown in Hydroponic Systems
Authors: Sumalan Radu Liviu , Nescu Vlad , Berbecea Adina , Sumalan Renata Maria , Crisan Manuela , Negrea Petru , Ciulca Sorin
Published: April 2023

Heavy metals like cadmium (Cd), copper (Cu), lead (Pb), and zinc (Zn), resulting from anthropogenic activities, are elements with high persistence in nature, being able to accumulate in soils, water, and plants with significant impact to human and animal health. This study investigates the phytoremediation capacity of Silphium perfoliatum L. as a specific heavy metal hyperaccumulator and the effects of Cu, Zn, Cd, and Pb on some physiological and biochemical indices by growing plants under floating hydroponic systems in nutrient solutions under the presence of heavy metals. One-year-old plants of S. perfoliatum grown for 20 days in Hoagland solution with the addition of (ppm) Cu-400, Zn-1200, Cd-20, Pb-400, and Cu+Zn+Cd+Pb (400/1200/20/400) were investigated with respect to the control. The level of phytoremediation, manifested by the ability of heavy metal absorption and accumulation, was assessed. In addition, the impact of stress on the proline content, photosynthetic pigments, and enzymatic activity, as being key components of metabolism, was determined. The obtained results revealed a good absorption and selective accumulation capacity of S. perfoliatum plants for the studied heavy metals. Therefore, Cu and Zn mainly accumulate in the stems, Cd in the roots and stems, while Pb mainly accumulates in the roots. The proline tended to increase under stress conditions, depending on the pollutant and its concentration, with higher values in leaves and stems under the associated stress of the four metals and individually for Pb and Cd. In addition, the enzymatic activity recorded different values depending on the plant organ, its type, and the metal concentration on its substrate. The obtained results indicate a strong correlation between the metal type, concentration, and the mechanisms of absorption/accumulation of S. perfoliatum species, as well as the specific reactions of metabolic response.
Integrated Analysis of miRNAome and Transcriptome Identify Regulators of Elm Seed Aging
Authors: Ye Tiantian , Huang Xu , Ma Tianxiao , Li Ying , Wang Xiaofeng , Lu Hai , Xue Hua
Published: April 2023

After maturity, seed vigor irreversibly decreases. Understanding the underlying mechanism is important to germplasm preservation. MicroRNAs (miRNAs) play vital regulatory roles in plants. However, little is known about how miRNAs regulate seed aging. Here, elm (Ulmus pumila L.) seeds of three aging stages were subjected to a multi-omics analysis including transcriptome, small RNAome and degradome, to find regulators of seed aging. In the small RNAome, 119 miRNAs were identified, including 111 conservative miRNAs and eight novel miRNAs specific to elm seeds, named upu-miRn1-8. A total of 4900 differentially expressed genes, 22 differentially expressed miRNAs, and 528 miRNA-target pairs were identified during seed ageing. The target genes were mainly involved in the processing of proteins in the endoplasmic reticulum, metabolism, plant hormone signal transduction, and spliceosome. The expression of several DEGs and miRNAs were verified by qRT-PCR. The degradome data showed the exact degradation sites of upu-miR399a on ABCG25, and upu-miR414a on GIF1, etc. The dual-luciferase assay verified the negative regulation of upu-miR399a on ABCG25 and upu-miR414a on GIF1 in tobacco leaves. This study outlined the regulation network of mRNA, miRNA and miRNA-target genes during seed aging, which is helpful in integrating the regulation mechanisms of seed vigor at the transcriptional and post-transcriptional levels.
The Lack of Standardization and Pharmacological Effect Limits the Potential Clinical Usefulness of Phytosterols in Benign Prostatic Hyperplasia
Authors: Buț Mădălina-Georgiana , Jîtcă George , Imre Silvia , Vari Camil Eugen , Ősz Bianca Eugenia , Jîtcă Carmen-Maria , Tero-Vescan Amelia
Published: April 2023

The prevalence of benign prostatic hyperplasia (BPH) markedly increases with age. Phytotherapeutic approaches have been developed over time owing to the adverse side effects of conventional medications such as 5-reductase inhibitors and α1-adrenergic receptor antagonists. Therefore, dietary supplements (DS) containing active compounds that benefit BPH are widely available. Phytosterols (PSs) are well recognized for their role in maintaining blood cholesterol levels; however, their potential in BPH treatment remains unexplored. This review aims to provide a general overview of the available data regarding the clinical evidence and a good understanding of the detailed pharmacological roles of PSs-induced activities at a molecular level in BPH. Furthermore, we will explore the authenticity of PSs content in DS used by patients with BPH compared to the current legislation and appropriate analytical methods for tracking DS containing PSs. The results showed that PSs might be a useful pharmacological treatment option for men with mild to moderate BPH, but the lack of standardized extracts linked with the regulation of DS containing PSs and experimental evidence to elucidate the mechanisms of action limit the use of PSs in BPH. Moreover, the results suggest multiple research directions in this field.
Antifungal Potency of Amaranth Leaf Extract: An In Vitro Study
Authors: Jamiołkowska Agnieszka , Skwaryło-Bednarz Barbara , Kowalski Radosław , Yildirim Ismet , Patkowska Elżbieta
Published: April 2023

Plant diseases are a serious problem for agricultural crops, the food industry and human health. Significant efforts have been made in recent years to find natural products that could reduce the growth of plant pathogens and improve food quality. At present, there is an increased interest in plants as a source of biological active compounds that can protect crops from diseases. Important sources of these phytochemicals are lesser-known pseudocereals such as amaranth. The objective of this study was to determine the antifungal activity of leaf extracts of four amaranth species (A. cruentus, A. hypochondriacus × hybridus, A. retroflexus and A. hybridus). The antifungal potency of amaranth extracts was analyzed against selected strains of fungi. The results suggested that the antimicrobial properties of the tested extracts varied depending on the amaranth species and the fungal strain. The studied extracts inhibited the growth of Fusarium equiseti, Rhizoctonia solani, Trichoderma harzianum and Alternaria alternata. A lower inhibitory effect of the extracts was recorded against F. solani, while no inhibitory effect was observed against F. oxysporum and Colletotrichum coccodes.
Dynamic Monitoring of Nutrition Inputs and Fertility Evaluation during a Decade in the Main Peach-Producing Areas of Shandong Province, China
Authors: Li Tingting , Zhang Binbin , Du Anqi , Yang Sankui , Huang Kexin , Peng Futian , Xiao Yuansong
Published: April 2023

The main peach-producing area in Shandong is an important peach fruit-producing area in China. Understanding the nutritional properties of the soil in peach orchards helps us to understand the evolution of soil properties and adjust management methods in a timely manner. This study focuses on 52 peach orchards in the main peach-producing area in Shandong as the research object. The spatiotemporal changes in soil traits and their influential factors were studied in depth, and the changes in soil fertility were effectively evaluated. The results showed that the input of nitrogen, phosphorus and potassium from organic fertilizer in 2021 was significantly higher than that in 2011, while the input of fertilizer in 2011 was significantly higher than that in 2021. Compared with traditional parks, both organic fertilizer inputs and chemical fertilizer inputs in demonstration parks showed a significant downwards trend. There was no significant change in pH values between 2011 and 2021. In 2021, the soil organic matter (SOM) contents of the 0–20 cm and 20–40 cm layers were 24.17 g·kg−1 and 23.38 g·kg−1, respectively, an increase of 29.3% and 78.47% over the values measured in 2011. Compared with 2011, the content of soil alkaloid nitrogen (AN) decreased significantly in 2021, and the contents of available phosphorus (AP) and available potassium (AK) in the soil increased significantly. According to the calculation results of the comprehensive fertility index (IFI) value, we found that in 2021, compared with 2011, the quality of soil fertility improved, most of which was at the medium and high levels. The research results show that the fertilizer-saving and synergistic approach in peach orchards in China significantly improved the soil nutrition. In the future, research on suitable comprehensive technologies should be strengthened in the management of peach orchards.