Construction of heterostructured Fe2O3/Fe7S8 hollow fibers to boost the electrochemical kinetics of lithium storage.

Heterostructured Fe2O3/Fe7S8 hollow fibers were rationally designed and synthesized via the electrospinning technique, followed by a calcination process and sulfuration treatment. Benefitting from the synergistic effect of the hollow structure and the built-in electric field induced by the heterostructure, the as-prepared Fe2O3/Fe7S8 composite anode exhibits high specific capacity (947 mA h g-1 after 100 cycles at 0.2 A g-1), excellent rate capability, and long-term cycling stability (730 mA h g-1 after 1000 cycles at 1 A g-1).

Discovery of a Novel Glucagon-like Peptide-1 (GLP-1) Analogue from Bullfrog and Investigation of Its Potential for Designing GLP-1-Based Multiagonists.

In this study, we aimed to discover novel GLP-1 analogues from natural sources. We investigated GLP-1 analogues from fish and amphibians, and bullfrog GLP-1 (bGLP-1) showed the highest potency. Starting with bGLP-1, we explored the structure-activity relationship and performed optimization and long-acting modifications, resulting in a potent analogue called 2f. Notably, 2f exhibited superior effects on food intake, glycemic control, and body weight compared to semaglutide. Furthermore, we explored the usefulness of bGLP-1 in designing GLP-1-based multiagonists. Using the bGLP-1 sequence, we designed novel dual GLP-1/glucagon receptor agonists and triple GLP-1/GIP/glucagon receptor agonists. The selected dual GLP-1/glucagon receptor agonist 3o and triple GLP-1/GIP/glucagon receptor agonist 4b exhibited significant therapeutic effects on lipid regulation, glycemic control, and body weight. Overall, our study highlights the potential of discovering potent GLP-1 receptor agonists from natural sources. Additionally, utilizing natural GLP-1 analogues for designing multiagonists presents a practical approach for developing antiobesity and antidiabetic agents.

Fusarium Wilt Invasion Results in a Strong Impact on Strawberry Microbiomes.

Plant-endophytic microbes affect plant growth, development, nutrition, and resistance to pathogens. However, how endophytic microbial communities change in different strawberry plant compartments after Fusarium pathogen infection has remained elusive. In this study, 16S and internal transcribed spacer rRNA amplicon sequencing were used to systematically investigate changes in the bacterial and fungal diversity and composition in the endophytic compartments (roots, stems, and leaves) of healthy strawberries and strawberries with Fusarium wilt, respectively. The analysis of the diversity, structure, and composition of the bacterial and fungal communities revealed a strong effect of pathogen invasion on the endophytic communities. The bacterial and fungal community diversity was lower in the Fusarium-infected endophytic compartments than in the healthy samples. The relative abundance of certain bacterial and fungal genera also changed after Fusarium wilt infection. The relative abundance of the beneficial bacterial genera Bacillus, Bradyrhizobium, Methylophilus, Sphingobium, Lactobacillus, and Streptomyces, as well as fungal genera Acremonium, Penicillium, Talaromyces, and Trichoderma, were higher in the healthy samples than in the Fusarium wilt samples. The relative abundance of Fusarium in the infected samples was significantly higher than that in the healthy samples, consistent with the field observations and culture isolation results for strawberry wilt. Our findings provide a theoretical basis for the isolation, identification, and control of strawberry wilt disease.

Synthesis and biological evaluation of capsaicin analogues as antioxidant and neuroprotective agents.

Capsaicin and its analogues 3a-3q were designed and synthesized as potential new antioxidant and neuroprotective agents. Many analogues exhibited good antioxidant effects, and some showed more potent free radical scavenging activities than the positive drug quercetin (IC50 = 8.70 ± 1.75 µM for DPPH assay and 13.85 ± 2.87 µM for ABTS assay, respectively). The phenolic hydroxyl of capsaicin analogues was critical in determining antioxidant activity. Among these compounds, 3k displayed the most potent antioxidant activity. Cell vitality tests revealed that the representative compound 3k was good at protecting cells from H2O2-induced oxidative damage at low concentrations (cell viability increased to 90.0 ± 5.5% at 10 µM). In addition, the study demonstrated that 3k could reduce intracellular ROS accumulation and increase GSH levels to prevent H2O2-induced oxidative stress in SY5Y cells. In the mitochondrial membrane potential assay, 3k significantly increased the MMP level of SY5Y cells treated with H2O2 and played an anti-neuronal cell death role. These results provide a promising strategy to develop novel capsaicin analogues as potential antioxidant and neuroprotective agents.

Design, synthesis, and evaluation of antitumor activity of novel C-6 sulfhydryl-substituted and 20-substituted derivatives of celastrol.

Celastrol has been identified as a potential candidate for anticancer drug development. In this study, 28 novel celastrol derivatives with C-6 sulfhydryl substitution and 20-substitution were designed and synthesized, and their antiproliferative activity against human cancer cells and non-malignant human cells was evaluated, with cisplatin and celastrol being used as controls. The results showed that most of the derivatives had enhanced in vitro anticancer activity compared to the parent compound celastrol. Specifically, derivative 2f demonstrated the most potent inhibitory potential and selectivity against HOS with an IC50 value of 0.82 µM. Our study provides new insights into the structure-activity relationship of celastrol and suggests that compound 2f may be a promising drug candidate for the treatment of osteosarcoma.

Discovery of a potent and long-acting Xenopus GLP-1-based GLP-1/glucagon/Y2 receptor triple agonist.

The combination of incretin-based therapies and PYY analogue has shown great potential for the treatment of type 2 diabetes (T2DM) and obesity. In this study we developed the first example of a unimolecular triple agonist peptide to simultaneously target GLP-1, glucagon and Y2 receptors, aiming for superior weight loss and better glycemic control. The strategy for constructing such a unimolecular triple agonist peptide is the conjugation of the GLP-1R/GCGR dual-agonistic moiety and PYY moiety via maleimide-thiol specific reaction. A novel triple agonist peptide, 3b, was identified via stepwise structure optimization, long-acting modification and in vitro receptor screens. Peptide 3b exhibited potent and balanced GCGR and GLP-1R activities as well as potent and highly selective Y2R activity. Peptide 3b potently reduced food intake without triggering nausea associated behavior in kaolin consumption and conditioned taste aversion assays. In diet induced obesity (DIO) mice, a lower dose of 3b achieved significantly better effects on lipid metabolism, body weight, and glycemic control than higher dose of GLP-1R mono-agonist, GLP-1R/GCGR dual agonist and GLP-1R/Y2R dual agonist counterparts. Collectively, these data support the therapeutic potential of our GLP-1R/GCGR/Y2R triple agonist 3b as a novel anti-obesity and anti-diabetic agent. Targeting GLP-1R, GCGR and Y2R with unimolecular triple agonist peptide offers a route to develop new obesity and T2DM treatments.

Design of Xenopus GLP-1-Based Long-Acting Dual GLP-1/Y2 Receptor Agonists.

GLP-1 receptor (GLP-1R) and neuropeptide Y2 receptor (Y2R) dual agonists have shown great potential to treat obesity and type 2 diabetes (T2DM). We developed a multitarget strategy to design monomeric agonists based on Xenopus GLP-1 (xGLP-1) and PYY3-36 analogues with dual activation activities on GLP-1R and Y2R. A novel peptide, 6q, was obtained via stepwise structure optimization and in vitro receptor screens. In db/db and diet-induced obesity (DIO) mice, 6q produced greater effects on long-term glycemic control and body weight reduction than GLP-1R and Y2R monoagonist counterparts. Notably, in high-fat diet-induced nonalcoholic steatohepatitis (NASH) mice, 6q treatment significantly reduced hepatic triglyceride and total cholesterol levels and reversed hepatic steatosis compared with GLP-1R monoagonist (liraglutide) treatment. Collectively, these data support the therapeutic potential of our GLP-1R/Y2R dual agonist 6q as a novel antidiabetic, antiobesity, and antisteatotic agent.

A GLP-1/glucagon (GCG)/CCK2 receptors tri-agonist provides new therapy for obesity and diabetes.

BACKGROUND AND PURPOSE: Glucagon-like peptide-1 (GLP-1) and glucagon (GCG) receptor dual agonist have promising therapeutic effects in the treatment of obesity and diabetes. Moreover, GLP-1 and cholecystokinin 2 (CCK2 ) dual agonists have been shown to restore pancreas function and improve glycaemic control in preclinical studies. We describe, for the first time, the beneficial effects of GLP-1/glucagon receptor and GLP-1/CCK2 dual agonists, which can be integrated into one peptide, resulting in significant anti-diabetes and anti-obesity effectiveness. EXPERIMENTAL APPROACH: The in vitro potency of this novel peptide Xenopus (x) GLP-1/GCG/CCK2 tri-agonist (xGLP/GCG/gastrin) against GLP-1, GCG, CCK1 and CCK2 receptors was determined on cells expressing the corresponding receptors by cAMP accumulation or ERK1/2 phosphorylation assays. The in vivo anti-diabetes and anti-obesity effects of this tri-agonist xGLP/GCG/gastrin were studied in both db/db and diet induced obesity (DIO) mice. KEY RESULTS: xGLP/GCG/gastrin was a potent and selective GLP-1, GCG and CCK2 tri-agonist. In DIO mice, the metabolic benefits of xGLP-1/GCG/gastrin, such as reduction of body weight and hepatic lipid contents were significantly better than those of the peptide ZP3022 (GLP-1/CCK-2 dual agonist) and liraglutide. In a short-term study in db/db mice, xGLP/GCG/gastrin treatment had considerable effects, increasing islet numbers, islet areas and insulin content. In a long-term treatment study using db/db mice, xGLP-1/GCG/gastrin showed a significantly and sustained improvement in glucose tolerance and glucose control compared with that of liraglutide, ZP3022, cotadutide (GLP-1/GCG dual agonist) and xGLP/GCG-15. CONCLUSIONS AND IMPLICATIONS: These results demonstrate the therapeutic potential of xGLP-1/GCG/gastrin for the treatment of obesity and diabetes.

Peptide-based long-acting co-agonists of GLP-1 and cholecystokinin 1 receptors as novel anti-diabesity agents.

The combined use of gastrointestinal hormones for treating metabolic diseases is gaining increasing attention. It was documented previously that co-administration of a cholecystokinin receptor-1 receptor (CCK-1R) agonist with a glucagon-like peptide-1 receptor (GLP-1R) agonist exerted improved effects on metabolic improvements in obese rodents. Here, we reported a series of novel GLP-1R/CCK-1R co-agonists constructed by linking the C-terminus of a GLP-1R agonist (native GLP-1 or Xenopus GLP-1) to the N-terminus of a CCK-1R selective agonist NN9056. The stability of co-agonists was further enhanced by introducing an albumin binding motif. In vitro functional assays revealed that the co-agonists retained full agonism potency on GLP-1R and CCK-1R. Particularly, 2a and 2c showed higher hypoglycemic and insulinotropic activities than NN9056 and semaglutide. The glucose-lowering durations and PK profiles of 2a and 2c were comparable to those of semaglutide. Desirably, in diet induced obesity (DIO) mice, 2a and 2c exhibited superior metabolic benefits to NN9056 and semaglutide in reducing food intake, inducing body weight loss, and regulating lipid metabolism. In short- and long-term studies in diabetic db/db mice, 2a and 2c showed enhanced effects on HbA1c, glucose tolerance, and pancreas function restoration compared with semaglutide. Importantly, no side effects, toxicities, or pancreatic inflammation were caused by 2a and 2c treatments. These preclinical studies suggest that the pharmacological effects of CCK-1 and GLP-1 pathways can be harnessed in a single fusion peptide, yielding a promising combination therapy strategy for treating metabolic disorders.

Self-assembly of core-shell structured multiwalled nanotubes@covalent organic frameworks composite for solid-phase extraction of four phytohormones from fruit juices.

Covalent organic frameworks (COFs) have attracted considerable attention in sample pretreatment because of their unique characteristics. However, the submicron or micron size of COFs has restricted their wider applications in solid-phase extraction (SPE). Herein, multiwalled nanotubes (MWNTs) were used as substrate materials to synthesize core-shell structured MWNTs@COFs composites (MWNTs@SNW-1) using a simple self-assembly method. The as-prepared MWNTs@SNW-1 composite exhibited a high BET surface area, good thermal stability, and good adsorption capacity. The MWNTs@SNW-1 composite was used as an adsorbent in cartridge-based SPE to extract four phytohormones before determining their levels by high-performance liquid chromatography. The experimental parameters affecting extraction efficiency, including the amount of adsorbents, solution pH, ionic strength, eluent type, and eluent volume, were investigated. The developed method showed a wide linear range (0.37-100 ng mL-1), low detection limits (0.11-0.32 ng mL-1), low limits of quantification (0.37-1.07 ng mL-1), high enrichment factors (45.9-49.3), and good reproducibility (<4.8%) for phytohormones. The developed analytical method was used to analyze trace phytohormones in fruit juices with good recoveries, highlighting the potential of the MWNTs@SNW-1 composite as an adsorbent in sample preparation.

High antibacterial activity of chitosan films with covalent organic frameworks immobilized silver nanoparticles.

In this study, chitosan (CS) film containing covalent organic frameworks (COFs) immobilized silver nanoparticles (AgNPs) were developed for food packaging with improved antibacterial activities and film properties. COFs-AgNPs were fabricated via in-situ synthesis of immobilizing AgNPs on COFs. Transmission electron microscope, Zeta potential, X-ray diffraction, element mapping and Fourier transform infrared spectroscopy confirmed the successful fabrication of COFs-AgNPs, and COFs-AgNPs showed superior antibacterial activity against S. aureus and E. coli. Furthermore, the as-prepared COFs-AgNPs composite was further used to fabricate CS composite films (CS/COFs-AgNPs) by a solution casting method. The findings showed that the tensile strength of the nanocomposite films enhanced dramatically with the increase of the COFs-AgNPs content, while the UV-visible light barrier property, water swelling and solubility properties, and water vapor permeability (WVP) decreased significantly. Not only that, the CS/COFs-AgNPs nanocomposite films also showed outstanding antibacterial activity and effectively prolonged the storage time of white crucian carp (Carassius auratus). As a result, CS/COFs-AgNPs nanocomposite films show great potential in active food packaging.

Degradation of aniline by ferrous ions activated persulfate: Impacts, mechanisms, and by-products.

Wastewater contains a large number of anions and organics which can scavenge reactive radicals and limit the application of sulfate radical-based advanced oxidation processes (SR-AOPs) in practical engineering. Here, we studied the removal rate and mechanism of aniline by SR-AOPs in different influencing factors, such as sodium persulfate dosage, ferrous ions dosage, solution pH, Cl-, HCO3-, NO3-, and other organic matter. By recognizing and analyzing free radicals, we concluded that SO4•- plays a major role in aniline degradation. The aniline removal rate increased with the initial concentrations of persulfate and ferrous ions, but aniline degradation was inhibited by excessive dosage. The aniline removal rate by ferrous-ions-catalyzed persulfate was higher under acidic conditions and could be improved under alkaline conditions if no ferrous ions were added. The addition of bicarbonate ions inhibited aniline removal, and the addition of nitrate ions barely caused the effect. While the addition of chloride ions promoted aniline degradation, which was confirmed that HClO generated from the reacting of Cl- and persulfate played a key role. However, TOC indicated that aniline was not completely mineralized in the process. Further analysis of the products from GC-MS demonstrated that chloride-ion additions produced some harmful halogenated by-products. Our results can act as a basis for developing processes for the aniline degradation in wastewater.

Sequencing, assembly, annotation, and gene expression: novel insights into browning-resistant Luffa cylindrica.

Luffa is a kind of melon crop widely cultivated in temperate regions worldwide. Browning is one of the serious factors affecting the quality of Luffa. Therefore, the molecular mechanism of Luffa browning is of great significance to study. However, the molecular diversity of Luffa cultivars with different browning-resistant abilities has not been well elucidated. In our study, we used high-throughput sequencing to determine the transcriptome of two Luffa cylindrica cultivars '2D-2' and '35D-7'. A total of 115,099 unigenes were clustered, of which 22,607 were differentially expression genes (DEGs). Of these DEGs, 65 encoding polyphenol oxidase, peroxidase, or ascorbate peroxidase were further analyzed. The quantitative real-time PCR (RT-qPCR) data indicated that the expression levels of the LcPPO gene (Accession No.: Cluster-21832.13892) was significantly higher in '35D-7' compared with that in '2D-2'. Several POD genes (Accession No.: Cluster-21832.19847, Cluster-21832.30619 and Cluster-48491.2) were also upregulated. Analysis of the plantTFDB database indicated that some transcription factors such as WRKY gene family may also participate in the regulation of Luffa browning. The results indicated that the divergence of genes expression related to enzymatic reaction may lead to the different browning resistances of Luffa. Our study will provide a theoretical basis for breeding of browning-resistant Luffa.

Genome-Wide Identification and Expression Analysis of the Strawberry FvbZIP Gene Family and the Role of Key Gene FabZIP46 in Fruit Resistance to Gray Mold.

A total of 54 FvbZIP genes were identified from the strawberry genome. These genes were found to be unevenly distributed on seven different chromosomes, and two of the genes had no matching chromosomal localization. FvbZIP genes were divided into 10 subfamilies according to protein sequence, and the structures of these genes were found to be highly conserved. Based on the bioinformatics analysis of FvbZIP genes, the expression of FabZIP genes changed during different stages of its growth and of its infection with gray mold disease. FabZIP46 was substantially upregulated, and its expression remained relatively high. FabZIP46 was cloned from cultivated strawberries by homologous cloning. The results of a transient transgenic assay revealed that the damage to the fruit tissue was markedly alleviated in strawberries overexpressing FabZIP46, with the incidence rate being substantially lower than that in the control group. By contrast, a brief silencing of FabZIP46 had the opposite effect. The results revealed that FabZIP46 played a positive role in the resistance of strawberries to Botrytis cinerea. The study findings provide valuable insights into the role of bZIP transcription factors as well as a theoretical reference for the regulation of resistance to gray mold disease in strawberry fruit.

Electrospinning fabrication of covalent organic framework composite nanofibers for pipette tip solid phase extraction of tetracycline antibiotics in grass carp and duck.

In the current study, a novel covalent organic frameworks COF-SCU1 incorporated electrospun nanofibers (PAN@COF-SCU1 nanofibers) was fabricated via a facile electrospinning method and utilized as adsorbent in pipette tip solid-phase extraction (PT-SPE) of tetracycline antibiotics (TCs) from foods. The prepared PAN@COF-SCU1 nanofibers possessed both of the unique characteristics of electrospun nanofibers and COFS-CU1, and thus improving the adsorption capacity of the electrospun nanofibers and preventing the problems of leakage and high pressure caused by directly using the nanosize COFs as adsorbent in PT-SPE. The experiments affected the adsorption and desorption efficiencies, such as the loading ratios of COFS-CU1 in nanofibers, the amount of nanofibers, the matrix pH and desorption solvent, were studied in detail. Eventually, a new pipette tip solid-phase extraction-high performance liquid chromatography (PT-SPE/HPLC) method was proposed for the analysis of three TCs from food. Satisfied linearity for TCs was obtained in the range of 4-70 ng mL-1. The limits of detection and quantification were ranged from 0.6 to 3 ng mL-1 and from 2 to 10 ng mL-1, respectively. The interday and intraday precisions (RSD) were all lower than 9%. The proposed PT-SPE/HPLC method was used to determine TCs residues in grass carp and duck samples for the first time. The results could not only explore the availability of PT-SPE in the extraction of TCs in food samples, but also broadened the potential applications of COFs in sample preparation.

Fabrication of Ligusticum chuanxiong polylactic acid microspheres: A promising way to enhance the hepatoprotective effect on bioactive ingredients.

Ligusticum chuanxiong extract-polylactic acid sustained-release microspheres (LCE-PLA) are fabricated in this study for enhancing both duration and hepatoprotective efficacy of the main bioactive ingredients. LCE-PLA in vitro release, cytotoxicity and in vivo hepatoprotective effect were discussed to evaluate its efficiency and functionality. Results demonstrated that the optimal drug-loading rate and encapsulation efficiency of tetramethylpyrazine (TMP, the main active ingredient) were 8.19%, 83.72%, respectively. The LCE-PLA in vitro release of TMP showed prolong 5-fold and in vitro cytotoxicity declined 25.00% compared with naked LCE. After 6 weeks of in vivo intervention in high fat diet mice, both liver aspartate aminotransferase and alanine aminotransferase levels were higher in LCE-PLA group than LCE group. The above results indicated that TMP had a higher bioavailability of hepatoprotection when encapsulation of LCE-PLA was applied. The current study has provided a promising novel way to enhance the efficacy of short half-life ingredients.

Asymmetric Total Synthesis of (-)-Guignardones A and B.

The asymmetric total synthesis of (-)-guignardones A (2) and B (1) has been accomplished. The highly oxidized 6-oxabicyclo[3.2.1]octane core was constructed from d-quinic acid via substitution/desulfurization reaction with thiophenol to forge the bridged ring scaffold, and a Pummerer rearrangement and 1,4-addition/elimination sequence was employed to install the ß-carbonyl group at the congested C-1 position. A late-stage Knoevenagel condensation-6π-electrocyclization and directed hydrogenation formed (-)-guignardone B (1), which was subjected to dehydration to furnish (-)-guignardone A (2).

Strawberry FaWRKY25 Transcription Factor Negatively Regulated the Resistance of Strawberry Fruits to Botrytis cinerea.

WRKY genes and jasmonic acid (JA) play a crucial role in plants' responses against biotic and abiotic stress. However, the regulating mechanism of WRKY genes on strawberry fruits' resistance against Botrytis cinerea is largely unknown, and few studies have been performed on their effect on the JA-mediated defense mechanism against B. cinerea. This study explored the effect of FaWRKY25 on the JA-mediated strawberry resistance against B. cinerea. Results showed that the JA content decreased significantly as the fruits matured, whereas the FaWRKY25 expression rose substantially, which led to heightened susceptibility to B. cinerea and in strawberries. External JA treatment significantly increased the JA content in strawberries and reduced the FaWRKY25 expression, thereby enhancing the fruits' resistance against B. cinerea. FaWRKY25 overexpression significantly lowered the fruits' resistance against B. cinerea, whereas FaWRKY25 silencing significantly increased resistance. Moreover, FaWRKY25 overexpression significantly lowered the JA content, whereas FaWRKY25 silencing significantly increased it. FaWRKY25 expression level substantially affects the expression levels of genes related to JA biosynthesis and metabolism, other members of the WRKY family, and defense genes. Accordingly, FaWRKY25 plays a crucial role in regulating strawberries' resistance against B. cinerea and may negatively regulate their JA-mediated resistance mechanism against B. cinerea.

Asymmetric Total Synthesis of (-)-Pavidolide B via a Thiyl-Radical-Mediated [3 + 2] Annulation Reaction.

The development of an efficient strategy for the asymmetric total synthesis of the bioactive marine natural product (-)-pavidolide B is described in detail. The development process and detours leading to the key thiyl-radical-mediated [3 + 2] annulation reaction, which constructed the central C ring with four contiguous stereogenic centers in one step, are depicted. Subsequently, the seven-membered D ring is constructed via a ring-closing metathesis reaction followed by a Rh(III)-catalyzed isomerization. This strategy enables the total synthesis of (-)-pavidolide B in the longest linear sequence of 10 steps.

Gibberellins Play a Role in Regulating Tomato Fruit Ripening.

Although exogenous applications of gibberellins (GAs) delay tomato ripening, the regulatory mechanisms of GAs in the process have never been well recognized. Here, we report that the concentration of endogenous GAs is declined before the increase of ethylene production in mature-green to breaker stage fruits. We further demonstrate that reductions in GA levels via overexpression of a GA catabolism gene SlGA2ox1 specifically in fruit tissues lead to early ripening. Consistently, we have also observed that application of a GA biosynthetic inhibitor, prohexadione-calcium, at the mature-green stage accelerates fruit ripening, while exogenous GA3 application delays the process. Furthermore, we demonstrate that ethylene biosynthetic gene expressions and ethylene production are activated prematurely in GA-deficient fruits but delayed/reduced in exogenous GA3-treated WT fruits. We also show that the GA deficiency-mediated activation of ethylene biosynthesis is due to the activation of the ripening regulator genes RIN, NOR and CNR. In conclusion, our results demonstrate that GAs play a negative role in tomato fruit ripening.