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This article is concerned with the existence of multiple normalized solutions for a class of Choquard equations with a parametric perturbation −ε2Δu+V(x)u=λu+ε−α(Iα*F(u))f(u),x∈RN,∫RN∣u∣2dx=a2εN,\left\{\begin{array}{ll}-{\varepsilon }^{2}\Delta u+V\left(x)u=\lambda u+{\varepsilon }^{-\alpha }\left({I}_{\alpha }* F\left(u))f\left(u),\hspace{1.0em}& x\in {{\mathbb{R}}}^{N},\\ \mathop{\displaystyle \int }\limits_{{{\mathbb{R}}}^{N}}{| u| }^{2}{\rm{d}}x={a}^{2}{\varepsilon }^{N},\hspace{1.0em}& \end{array}\right. where a>0a\gt 0 is a constant, ε>0\varepsilon \gt 0 is a parameter, N≥3N\ge 3, α∈(0,N)\alpha \in \left(0,N), λ∈R\lambda \in {\mathbb{R}} is unknown and appears as a Lagrange multiplier, ff is a continuous function with L2{L}^{2}-subcritical growth, and V:RN→[0,∞)V:{{\mathbb{R}}}^{N}\to \left[0,\infty ) is a continuous function, satisfying del Pino and Felmer’s local conditions. With the help of the penalization method, and Lusternik-Schnirelmann theory, we investigate the relationship between the number of positive normalized solutions and the topology of the set, where the potential VV attains its minimum value if the parameter ε>0\varepsilon \gt 0 is small.

Wild and weedy relatives of domesticated crops harbor genetic variants that can advance agricultural biotechnology. Here we provide a genome resource for the wild plant green millet (Setaria viridis), a model species for studies of C4 grasses, and use the resource to probe domestication genes in the close crop relative foxtail millet (Setaria italica). We produced a platinum-quality genome assembly of S. viridis and de novo assemblies for 598 wild accessions and exploited these assemblies to identify loci underlying three traits: response to climate, a 'loss of shattering' trait that permits mechanical harvest and leaf angle, a predictor of yield in many grass crops. With CRISPR-Cas9 genome editing, we validated Less Shattering1 (SvLes1) as a gene whose product controls seed shattering. In S. italica, this gene was rendered nonfunctional by a retrotransposon insertion in the domesticated loss-of-shattering allele SiLes1-TE (transposable element). This resource will enhance the utility of S. viridis for dissection of complex traits and biotechnological improvement of panicoid crops.

Doxorubicin (Dox) is a highly effective anti‐neoplastic agent. Still, its utility in the clinic has been hindered by toxicities, including vomiting, hematopoietic suppression and nausea, with cardiotoxicity being the most serious side effect. Genistein (Gen) is a natural product with extensive biological effects, including anti‐oxidation, anti‐tumor, and cardiovascular protection. This study evaluated whether Gen protected the heart from Dox‐induced cardiotoxicity and explored the underlying mechanisms. Male Sprague–Dawley (SD) rats were categorized into control (Ctrl), genistein (Gen), doxorubicin (Dox), genistein 20 mg/kg/day + doxorubicin (Gen20 + Dox) and genistein 40 mg/kg/day + doxorubicin (Gen40 + Dox) groups. Six weeks after injection, immunohistochemistry (IHC), transmission electron microscopy (TEM), and clinical cardiac function analyses were performed to evaluate the effects of Dox on cardiac function and structural alterations. Furthermore, each heart histopathological lesions were given a score of 0–3 in compliance with the articles for statistical analysis. In addition, molecular and cellular response of H9c2 cells toward Dox were evaluated through western blotting, Cell Counting Kit‐8 (CCK8), AO staining and calcein AM/PI assay. Dox (5 μM in vitro and 18 mg/kg in vivo) was used in this study. In vivo, low‐dose Gen pretreatment protected the rat against Dox‐induced cardiac dysfunction and pathological remodeling. Gen inhibited extracellular signal‐regulated kinase1/2 (ERK1/2)'s phosphorylation, increased the protein levels of STAT3 and c‐Myc, and decreased the autophagy and apoptosis of cardiomyocytes. U0126, a MEK1/2 inhibitor, can mimic the effect of Gen in protecting against Dox‐induced cytotoxicity both in vivo and in vitro. Molecular docking analysis showed that Gen forms a stable complex with ERK1/2. Gen protected the heart against Dox‐induced cardiomyocyte autophagy and apoptosis through the ERK/STAT3/c‐Myc signaling pathway. [ABSTRACT FROM AUTHOR]

Growth hormone deficiency (GHD) and idiopathic short stature (ISS) are the most common types of short stature (SS), but little is known about their pathogenesis, and even less is known about the study of adolescent SS. In this study, nuclear magnetic resonance (NMR)-based metabolomic analysis combined with least absolute shrinkage and selection operator (LASSO) were performed to identify the biomarkers of different types of SS (including 94 preadolescent GHD (PAG), 61 preadolescent ISS (PAI), 43 adolescent GHD (ADG), and 19 adolescent ISS (ADI)), and the receiver operating characteristic curve (ROC) was further used to evaluate the predictive power of potential biomarkers. The results showed that fourteen, eleven, nine, and fifteen metabolites were identified as the potential biomarkers of PAG, PAI, ADG, and ADI compared with their corresponding controls, respectively. The disturbed metabolic pathways in preadolescent SS were mainly carbohydrate metabolism and lipid metabolism, while disorders of amino acid metabolism played an important role in adolescent SS. The combination of aspartate, ethanolamine, phosphocholine, and trimethylamine was screened out to identify PAI from PAG, and alanine, histidine, isobutyrate, methanol, and phosphocholine gave a high classification accuracy for ADI and ADC. The differences in metabolic characteristics between GHD and ISS in preadolescents and adolescents will contribute to the development of individualized clinical treatments in short stature. [ABSTRACT FROM AUTHOR]

Plastid terminal oxidases (PTOXs) are essential for maintaining photosynthetic efficiency and cellular redox homeostasis. Astaxanthin, a carotenoid pigment with antioxidant properties, is synthesized and accumulates in response to oxidative stress induced by high-light intensity or nutrient limitation. It suggests that PTOX may impact astaxanthin biosynthesis under environmental stress conditions due to its involvement in ROS regulation. The ptox1 gene is thought to have a conserved role in safeguarding the photosynthetic apparatus from over-reduction and participating in energy dissipation. On the other hand, the ptox2 gene seems to be involved in the evolution of astaxanthin synthesis and adaptive responses to diverse environmental stressors. Efficient gene silencing strains were developed in Chlamydomonas reinhardtii CC849 for ptox1 and ptox2. The study found that the ptox2 gene correlates highly with resistance to intense light stress. Furthermore, the ptox2 gene showed increased activity under high salt stress conditions, indicating its importance in stress coping mechanisms. The quantification of astaxanthin in the gene-silenced strains revealed that ptox1 acts as a positive regulator, while ptox2 functions as a negative regulator of astaxanthin accumulation. Understanding the coordination between ptox1 and ptox2 could clarify the synergistic actions of these genes in maintaining photosynthetic performance and redox balance under fluctuating environmental conditions. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to identify the differential metabolic characteristics of children with overweight and obesity and understand their potential mechanism in different age stratifications. Methods: Four hundred seventy‐three children were recruited and divided into two age stratifications: >4 years (older children) and ≤4 years (younger children), and overweight and obesity were defined according to their BMI percentile. A one dimensional proton nuclear magnetic resonance (1H‐NMR)–based metabolomics strategy combined with pattern recognition methods was used to identify the metabolic characteristics of childhood overweight and obesity. Results: Four and sixteen potential biomarkers related to overweight and two and twenty potential biomarkers related to obesity were identified from younger and older children, respectively. Fluctuations in phenylalanine, tyrosine, glutamine, leucine, histidine, and ascorbate co‐occurred in children with obesity at two age stratifications. The disturbances in biosynthesis and metabolism of amino acids, lipid metabolism, and galactose metabolism disturbance were mainly involved in children with overweight and obesity. Conclusions: The metabolic disturbances show a significant progression from overweight to obesity in children, and different metabolic characteristics were demonstrated in age stratifications. The changes in the levels of phenylalanine, tyrosine, glutamine, leucine, histidine, and ascorbate were tracked with the persistence of childhood obesity. These findings will promote the mechanistic understanding of childhood overweight and obesity. [ABSTRACT FROM AUTHOR]

Purpose: Child malnutrition is a global public health problem, but the underlying pathophysiologic mechanisms with severity remain poorly understood, and the potential biomarkers served to the clinical diagnosis are still not available. This study aimed to identify the serum metabolic characteristics of malnourished children with severity. Methods: Fasted overnight serum samples were collected following clinical standard procedures among 275 malnourished and 199 healthy children from the Women and Children's Hospital, Xiamen University Child Health Department from July 2020 to May 2022. Nuclear magnetic resonance (NMR)-based metabolomics strategy was applied to identify the potential serum biomarkers of malnutrition from 275 malnourished children aged 4 to 84 months with mild (Mil, 199 cases), moderate (Mod, 101 cases), and severe (Sev, 7 cases) malnutrition. Results: Ten, fifteen, and fifteen differential metabolites were identified from the Mil, Mod, and Sev malnutrition groups, respectively. Eight common metabolites, including increased acetoacetate, acetone, ethanol, succinate, 3-hydroxybutyrate, and decreased alanine, methionine, and N-acetyl-glycoprotein, could be the potential biomarkers for malnourished children. The altered metabolic pathways were mainly related to energy metabolism and amino acid metabolism via the network-based pathway enrichment. Conclusion: Eight potential biomarkers, including acetoacetate, acetone, ethanol, succinate, 3-hydroxybutyrate, alanine, methionine, and N-acetyl-glycoprotein, could characterize the child malnutrition. Child malnutrition-induced abnormal energy metabolism, impaired nutrition utilization and the reduced nutrient availability, and more metabolic disturbance will appear with the severity. Our results are valuable for further studies on the etiology and pathogenesis of malnutrition for clinical intervention and improvement. [ABSTRACT FROM AUTHOR]