Changes in mineral nutrition during fruit growth and development of ‘Seike’ and ‘Newhall’ navel orange as a guide for fertilization

Abstract Changes in the accumulation patterns of mineral nutrients at different development stages of fruit reflect the requirements of citrus trees for different nutrients, and this information provides an essential reference for rational fertilization. In this study, changes in the contents of 11 nutrients in the whole fruit, fruit pulp, and peel were studied during the whole developmental period of the fruit of ‘Seike’ and ‘Newhall’ navel oranges. We found that the two navel orange cultivars showed very similar changes in nutrients. Specifically, the N, P, Mg, S, Mn, and Zn contents were high in the young fruit stage (April), the K and Fe contents were high in the fruit expansion stage (July and August), and the Ca content was high in the fruit maturation stage (October). As the fruit developed, the N, P, Mg, S, Zn, and B contents decreased to the lowest levels at fruit maturity in November. In addition, the contents of N, P, K, Fe, Zn, and Cu were ranked as fruit pulp > whole fruit > peel, while Ca, Mn, and B contents were ranked as fruit peel > whole fruit > fruit pulp. N, P, K, and Mg accumulated in the fruit in June and July, in contrast to the June to September period for the micro-elements. During these accumulation periods, it is recommended that suitable fertilizers be applied in a timely manner.</div

Data_Sheet_1_Favoring Expression of Yak Alleles in Interspecies F1 Hybrids of Cattle and Yak Under High-Altitude Environments.docx

Both cis- and trans-regulation could cause differential expression between the parental alleles in diploid species that might have broad biological implications. Due to the relatively distant genetic divergence between cattle and yak, as well as their differential adaptation to high-altitude environments, we investigated genome-wide allelic differential expression (ADE) in their F1 hybrids using Nanopore long-read RNA-seq technology. From adult F1 hybrids raised in high-altitude, ten lung and liver tissues were individually sequenced for producing 31.6 M full-length transcript sequences. Mapping against autosomal homologous regions between cattle and yak, we detected 17,744 and 14,542 protein-encoding genes expressed in lung and liver tissues, respectively. According to the parental assignments of transcript sequences, a total of 3,381 genes were detected to show ADE in at least one sample. There were 186 genes showing ubiquitous ADE in all the studied animals, and among them 135 and 37 genes had consistent higher expression of yak and cattle alleles, respectively. Functional analyses revealed that the genes with favoring expression of yak alleles have been involved in the biological progresses related with hypoxia adaptation and immune response. In contrast, the genes with favoring expression of cattle alleles have been enriched into different biological progresses, such as secretion of endocrine hormones and lipid metabolism. Our results would support unequal contribution of parental genes to environmental adaptation in the F1 hybrids of cattle and yak.</p

Table_1_Real-world national trends and socio-economic factors preference of sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists in China.docx

BackgroundsRobust evidence have demonstrated the beneficial effect of Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) in T2D patients with cardiovascular diseases and chronic kidney disease. Multiple studies analyzed patterns and predictors of SGLT2i and GLP-1RA in the US, Europe and worldwide. However, there is no study about the utilization of these two classes of drugs in real-world in China.MethodA total of 181743 prescriptions of SGLT2i and 59720 GLP-1RA were retrospectively pooled from Hospital Prescription Analysis Cooperation Project from 2018 to 2021. The social-economic characteristics of patients and prescribers, including age, gender, residency, hospital level, insurance type, department visited, and payment amount, were collected and analyzed to study trends and risk factors associated with preference among two antidiabetics.ResultsAnnual number of prescriptions of SGLT2i significantly increased to approximately 140 folds, while GLP-1RA increased to about 6.5 folds. After adjustment for socio-economic information, several patients or physician characteristics were positively associated with the preference of GLP-1RA, including female gender (OR 1.581, 95% CI 1.528-1.635), residents in second-tier cities (OR 1.194, 95% CI 1.148-1.142), visiting primary or secondary hospital level (OR 2.387, 95% CI 2.268-2.512); while other factors were associated with the preference of SGLT2i, including older adults (OR 0.713, 95% CI 0.688-0.739), uncovered by insurance (OR 0.310, 95% CI 0.293-0.329), visiting other departments compared with endocrinology. In addition, the share of SGLT2i and GLP-1RA was low but in an increasing tendency.ConclusionsSGLT2i and GLP-1RA prescription significantly increased from 2018 to 2021. The socio-economic risk factors in choosing SGLT2i or GLP-1RA highlight an effort required to reduce disparities and improve health outcomes.</p

Photoresponsive “Smart Template” via Host–Guest Interaction for Reversible Cell Adhesion

Photoresponsive “Smart Template” via Host–Guest Interaction for Reversible Cell Adhesio

Table_2_Utilization of glucagon-like peptide-1 receptor agonists in children and adolescents in China: a real-world study.docx

BackgroundGlucagon-like peptide-1 receptor agonists (GLP-1RAs) have been widely used in treating type 2 diabetes mellitus (T2DM) and obesity in adults, but scientific research about the indication in children and adolescents is scarce. The current study aims to explore the prescriptions of GLP-1RAs in children and adolescents in China and to evaluate its rationality.MethodsGLP-1RA prescriptions of children and adolescents were retrospectively obtained from the Hospital Prescription Analysis Cooperative Project. The study extracted information on patient’s demographic characteristics, monotherapy and combination therapy of GLP-1RAs, and trends in GLP-1RA usage from 2016 to 2021. The rationality of GLP-1RA prescriptions was comprehensively assessed based on the indications approved by China National Medical Products Administration (NMPA), the U.S. Food and Drug Administration (FDA), European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), and published randomized controlled trials (RCTs).ResultsA total of 234 prescriptions from 46 hospitals were included, with a median age of 17 years old. The majority of patients were diagnosed with overweight/obesity or prediabetes/diabetes, accounting for 43.59% and 46.15%, respectively. There were 88 patients on GLP-1RA monotherapy. GLP-1RAs plus metformin was the most common combination therapy (38.89%). 12.39% of patients were found a co-administration with orlistat. The share of overweight/obesity prescriptions increased from 27% in 2016 to 54% in 2021, whereas prediabetes/diabetes prescriptions declined from 55% to 42%. The prescriptions were divided into appropriate and questionable groups according to the diagnosis, and the potentially questionable prescription was related to age (p = 0.017), department visited (p = 0.002), and any hospitalization (p ConclusionsThis study described the prescribing of GLP-1RAs in children and adolescents. Our findings indicated that the utilization of GLP-1RAs has increased from 2016 to 2021. There was a strong basis for administering GLP-1RAs in overweight/obesity and prediabetes/diabetes, whereas the evidence was insufficient in other conditions. It is crucial to demand robust and sustained efforts to enhance the awareness of the safety of utilization of GLP-1RAs in children and adolescents.</p

Feasibility Study on Prenatal Cardiac Screening Using Four-Dimensional Ultrasound with Spatiotemporal Image Correlation: A Multicenter Study - Fig 1

<p>Multiplanar mode (4CV as the original acquisition plane): (A) 4CV; (B) DA; (C) transverse section of plane A. LV, left ventricle; RV, right ventricle; LA, left atrium; RA, right atrium; DAO, descending aorta; RVOT, right ventricular outflow tract; 4CV, four-chamber view; DA, ductal arch.</p

Degradable Mesoporous Silica Nanoparticle/Peptide-Based “Trojan Horse”-like Drug Delivery System for Deep Intratumoral Penetration and Cancer Therapy

For conventional anticancer drug delivery systems (DDSs), it is difficult to endow them with both long circulation in vivo and easy cellular endocytosis by cancer cells as well as the ability to accumulate in tumors through the enhanced permeability and retention (EPR) effect and deep intratumoral penetration. Therefore, their in vivo treatment effects are inadequate. Previous studies have shown that “dynamic protection” strategies can effectively address the difficulty of DDS entry into cancer cells as a result of modifying “stealthy” molecules such as poly­(ethylene glycol) (PEG). In this work, a “Trojan horse”-like DDS was fabricated by employing the “dynamic protection” strategy. The DDS was developed using ultrasmall, degradable mesoporous silica nanoparticles (DS-MSN) that were bridged by a degradable peptide and cross-linked with 4-arm PEG-N3 through click chemistry. This resulted in DOX-DS-MSN-CD-peptide-PEG with a size of ∼300 nm, which could accumulate in the tumor, following adequate blood circulation. The peptide could be degraded by matrix metalloproteinase-2 (MMP-2), an overexpressed enzyme in tumors, leading to the release of small-sized, tumor-permeable DS-MSN-based carriers. The remaining Arg-Gly-Asp (RGD) peptide on the surface provides the carriers with a “tumor-triggered targeting” capability. DS-MSN, which includes disulfide bonds in its backbone, could be degraded due to glutathione (GSH) in cancer cells and release of the loaded doxorubicin hydrochloride (DOX). In vitro and in vivo experiments showed that DOX-DS-MSN-CD-peptide-PEG had a prolonged circulation time and tumor accumulation ability, excellent tumor penetration ability, and controlled drug release ability. It operated like a “Trojan horse”, overcoming obstacles to deliver the “Greek soldier” DOX to the interior of cancer cells, resulting in effective tumor suppression. This study offers interesting concepts for designing effective and safe drug delivery systems

Cyclodextrin-Responsive Micelles Based on Poly(ethylene glycol)–Polypeptide Hybrid Copolymers as Drug Carriers

Novel drug carriers based on poly­(ethylene glycol) (PEG)–polypeptide copolymers, four-armed poly­(ε-adamantane-l-lysine)₂-block-poly­(ethylene glycol)-block-poly­(ε-adamantane-l-lysine)₂ (PLys­(Ad)₂-<i>b</i>-PEG-<i>b</i>-PLys­(Ad)₂), have been prepared. The copolymers were synthesized via the ring-opening polymerization of amino acid <i>N</i>-carboxyanhydrides. The copolymers could spontaneously form core–shell micelles in aqueous solutions. It has been found that these micelles undergo triggered disassembly in response to an additional β-cyclodextrin (β-CD). The in vitro drug release in response to β-CD has been studied, and the result shows that the release of the entrapped drug doxorubicin (DOX) from the micelles could be accelerated by the addition of β-CD. Their cytotoxicity and cell internalization behavior were also investigated in detail. These micelles are expected to have great potential in controlled drug release applications

Core−Shell Nanosized Assemblies Mediated by the α−β Cyclodextrin Dimer with a Tumor-Triggered Targeting Property

In this paper, the α−β cyclodextrin dimer is designed via “click” chemistry to connect the hydrophilic and hydrophobic segments to form self-assembled noncovalently connected micelles (NCCMs) through host−guest interactions. A peptide containing the Arg-Gly-Asp (RGD) sequence was introduced to NCCMs as a target ligand to improve the cell uptake efficacy, while PEGylated technology was employed via benzoic-imine bonds to protect the ligands in normal tissues and body fluid. In addition, two fluorescent dyes were conjugated to different segments to track the formation of the micelles as well as the assemblies. It was found that the targeting property of NCCMs was switched off before reaching the tumor sites and switched on after removing the poly(ethylene glycol) (PEG) segment in the tumor sites, which was called “tumor-triggered targeting”. With deshielding of the PEG segment, the drugs loaded in NCCMs could be released rapidly due to the thermoinduced phase transition. The new concept of “tumor-triggered targeting” proposed here has great potential for cancer treatment