Towards promoting wound healing: A near-infrared light-triggered persistently antibacterial, synergistically hemostatic nanoarchitecture-integrated chitosan hydrogel.

The skin, the primary barrier of the body, is inevitably broken. However, the development of materials that facilitate wound healing with sustained antimicrobial, hemostatic, and biocompatible properties remains a formidable challenge. In this article, we prepared a photopolymerizable composite hydrogel consisting of a hydrogel matrix, a hemostatic/antibacterial agent, and a photothermal therapy agent. The photopolymerizable hydrogel matrix was prepared by grafting the photoinitiator and polymerizable active monomer onto the chitosan chain segment, which exhibits excellent biocompatibility. Furthermore, linalool is adsorbed on the surface of halloysite nanotubes (HNTs) to form a hemostatic and antibacterial. Meanwhile, dopamine is employed as a coating material for hollow glass microsphere (HGM), which enables them to function as photothermal therapy agents. Upon exposure to near-infrared radiation, the PHA hydrogel releases linalool molecules from the surface of the HNTs, which diffuse into the hydrogel matrix, resulting in a sustained antimicrobial effect. At the same time, rapid curing of the photopolymerizable hydrogel under UV light forms a physical barrier that synergistically enhances the hemostatic properties of the HNTs. From the above, the results pave the way to develop a potential hemostatic antimicrobial dressing for clinical use in wound healing.

Zwitterion-Modified Nanogel Responding to Temperature and Ionic Strength: A Dissipative Particle Dynamics Simulation.

The self-assembly and stimuli-responsive properties of nanogel poly(n-isopropylacrylamide) (p(NIPAm)) and zwitterion-modified nanogel poly(n-isopropylacrylamide-co-sulfobetainemethacrylate) (p(NIPAm-co-SBMA)) were explored by dissipative particle dynamics simulations. Simulation results reveal that for both types of nanogel, it is beneficial to form spherical nanogels at polymer concentrations of 5-10%. When the chain length (L) elongates from 10 to 40, the sizes of the nanogels enlarge. As for the p(NIPAm) nanogel, it shows thermoresponsiveness; when it switches to the hydrophilic state, the nanogel swells, and vice versa. The zwitterion-modified nanogel p(NIPAm-co-SBMA) possesses thermoresponsiveness and ionic strength responsiveness concurrently. At 293 K, both hydrophilic p(NIPAm) and superhydrophilic polysulfobetaine methacrylate (pSBMA) could appear on the outer surface of the nanogel; however, at 318 K, superhydrophilic pSBMA is on the outer surface to cover the hydrophobic p(NIPAm) core. As the temperature rises, the nanogel shrinks and remains antifouling all through. The salt-responsive property can be reflected by the nanogel size; the volumes of the nanogels in saline systems are larger than those in salt-free systems as the ionic condition inhibits the shrinkage of the zwitterionic pSBMA. This work exhibits the temperature-responsive and salt-responsive behavior of zwitterion-modified-pNIPAm nanogels at the molecular level and provides guidance in antifouling nanogel design.

Awakening Allies for Breaking Microenvironment Barriers: NIR-II Guided Orthogonal Activation of Tumor-Infiltrating Mast Cells for Efficient Nano-Drug Delivery.

Mast cells (MCs), powerful immune cells that heavily infiltrate cancer cells, play a crucial role in tumor formation. Activated MCs can release histamine and a family of proteases through degranulation effects, concurrently achieving endothelial junction weakening and stromal degradation of the tumor microenvironment, thereby clearing the obstacles for nano-drug infiltration. To achieve precise activation of tumor-infiltrating MCs, orthogonally excited rare earth nanoparticles (ORENP), with two channels, are introduced for the controllable stimulating drugs release wrapped in "photocut tape". The ORENP can emit near-infrared II (NIR-II) for image tracing for tumor localization in Channel 1 (808/NIR-II) and allows energy upconversion to emit ultraviolet (UV) light for releasing drugs for MCs stimulation in Channel 2 (980/UV). Finally, the combined use of chemical and cellular tools enables clinical nano-drugs to achieve a significant increase in tumor infiltration, thereby enhancing the efficacy of nano-chemotherapy.

Exocarpium Citri Grandis alleviates the aggravation of NAFLD by mitigating lipid accumulation and iron metabolism disorders.

ETHNOPHARMACOLOGICAL RELEVANCE: Exocarpium Citri grandis (ECG, Huajuhong in Chinese), the epicarp of C. grandis 'Tomentosa', has been used for hundreds of years as an anti-inflammatory, expectorant, hypoglycemic, and lipid-lowering medication in China. Nevertheless, there have been few papers that have explored the mechanism behind ECG's hypolipidemic characteristics from the perspective of treating nonalcoholic fatty liver disease (NAFLD). AIM OF STUDY: The purpose of our study was to confirm the therapeutic and preventative effects of ECG in NAFLD by regulating lipid accumulation and iron metabolism, and to explore the specific mechanism of ECG in enhancing hepatic iron transport and excretion capabilities. STUDY DESIGN: We constructed a NAFLD model by feeding male C57BL/6 J mice with a high-fat diet for 12 weeks. Mice were gavaged with ECG beginning in the seventh week of modeling, and three dosage gradients were established: low dose group (2.5 g/kg/d), medium dose group (5 g/kg/d) y, and high dose group (10 g/kg/d) until the end of model construction in week 12. MATERIALS AND METHODS: We used network pharmacology to analyze the relationship between ECG and NAFLD. In addition, we constructed a nonalcoholic fatty liver disease model by feeding male C57BL/6 J mice a high-fat diet for 12 weeks. Finally, lipid accumulation, iron accumulation, inflammation and oxidative stress were evaluated by serological index detection, histological detection, immunofluorescent and immunohistochemical staining, and western blotting. RESULTS: Network pharmacology confirmed the treatment effect of ECG in NAFLD. Three active components of ECG, including Naringenin, Naringin and Neohesperidin, were detected by UHPLC-HRMS analysis. The results of serum TC, TG, LDL concentration, HE staining, Oil red staining and Nile red staining demonstrated that ECG could improve lipid metabolism disorders. The results of serum iron concentration, liver tissue iron concentration, iron metabolism-related proteins Ferritin light chain, Ferroportin1, Transferrin receptor, and Transferrin demonstrated that ECG improved the iron transport and storage capacities of hepatic cells. CONCLUSIONS: Our results demonstrated that ECG relieved liver injury by inhibiting lipid accumulation and iron accumulation in NAFLD.

Multifunctional Nanoplatform for Mild Microwave-Enhanced Thermal, Antioxidative, and Chemotherapeutic Treatment of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is usually associated with excessive proliferation of M1-type proinflammatory macrophages, resulting in severe hypoxia and excess reactive oxygen species (ROS) in the joint cavity. Inhibiting M1-type proinflammatory macrophages and/or repolarizing them into M2 phenotype anti-inflammatory cells by alleviating hypoxia and scavenging ROS could be a promising strategy for RA treatment. In this work, a microwave-sensitive metal-organic framework of UiO-66-NH2 is constructed for coating a nanoenzyme of cerium oxide (CeO2) and loading with the drug celastrol (Cel) to give UiO-66-NH2/CeO2/Cel, which is ultimately wrapped with hyaluronic acid (HA) to form a nanocomposite UiO-66-NH2/CeO2/Cel@HA (UCCH). With the microwave-susceptible properties of UiO-66-NH2, the thermal effect of microwaves can eliminate the excessive proliferation of inflammatory cells. In addition, superoxide-like and catalase-like activities originating from CeO2 in UCCH are boosted to scavenge ROS and accelerate the decomposition of H2O2 to produce O2 under microwave irradiation. The nonthermal effect of microwaves could synergistically promote the repolarization of M1-type macrophages into the M2 phenotype. Accompanied by the release of the anti-RA chemotherapeutic drug Cel, UCCH can efficiently ameliorate RA in vitro and in vivo through microwave-enhanced multisynergistic effects. This strategy could inspire the design of other multisynergistic platforms enhanced by microwaves to exploit new treatment modalities in RA therapies.

LnNP@ZIF8 Smart System for In Situ NIR-II Ratiometric Imaging-Based Tumor Drug Resistance Evaluation.

Just-in-time evaluation of drug resistance in situ will greatly facilitate the achievement of precision cancer therapy. The rapid elevation of reactive oxygen species (ROS) is the key to chemotherapy. Hence, suppressed ROS production is an important marker for chemotherapy drug resistance. Herein, a NIR-II emission smart nanoprobe (LnNP@ZIF8, consisting of a lanthanide-doped nanoparticle (LnNP) core and metal-organic framework shell (ZIF8)) is constructed for drug delivery and in vivo NIR-II ratiometric imaging of ROS for tumor drug resistance evaluation. The drug-loaded nanoprobes release therapeutic substances for chemotherapy in the acidic tumor tissue. As the level of ROS increases, the LnNPs shows responsively descending fluorescence intensity at 1550 nm excited by 980 nm (F1550, 980Ex), while the fluorescence of the LnNPs at 1060 nm excited by 808 nm (F1060, 808Ex) is stable. Due to the ratiometric F1550, 980Ex/F1060, 808Ex value exhibiting a linear relationship with ROS concentration, NIR-II imaging results of ROS change based on this ratio can be an important basis for determining tumor drug resistance. As the chemotherapy and resistance evaluation are explored continuously in situ, the ratiometric imaging identifies drug resistance successfully within 24 h, which can greatly improve the timeliness of accurate treatment.

Photochemically Driven Polymeric Biocompatible and Antimicrobial Thiol-Acrylate Nanocomposite Suitable for Dental Restoration.

The development a photochemically driven polymeric composite for dental restorative materials to restore tooth cavities with antibacterial, biocompatibility, and outstanding mechanical properties is an urgent need for clinical application in stomatology. Herein, a series of polyurethane acrylate (PUA) prepolymers and antibacterial polyurethane acrylate quaternary ammonium salts (PUAQASs) were synthesized, and their mechanical and biological properties were explored. The unique secondary mercaptan with a long shelf life and low odor was used to reduce oxygen inhibition and increase cross-linking density; meanwhile, modified photocurable nano zirconia (nano ZrO2) enhances mechanical properties of the nanocomposites and possesses preeminent dispersion in the matrix. The results show that minimal inhibitory concentrations (MICs) of PUAQASs are 200 and 800 µg/mL for Staphylococcus aureus and Escherichia coli, respectively. The addition of secondary thiols significantly increases the photopolymerization rate and monomer conversion. The highest hardness and modulus reach 1.8 and 8.7 GPa compared to 1.8 and 8.3 GPa for commercial resin. The lap shear stress on the pig bone is 912 MPa, and that on commercial resin is 921 MPa. Most importantly, the photochemically driven polymeric composite has excellent biocompatibility and significantly better antimicrobial properties than commonly used commercial resins.

The Exogenous Application of Micro-Nutrient Elements and Amino Acids Improved the Yield, Nutritional Status and Quality of Mango in Arid Regions.

The mango is one of the most valuable and appealing tropical fruits due to its color, aroma, tasteful remarkable flavor, and nutritive value; however, improving the yield and quality of mango is an urgent goal in order to combat global population growth. The application of amino acids and a micronutrient mixture might improve the yield and quality features but further research is still required in arid regions. To study the combined effect of a micronutrient mixture (MM) and amino acids (AA) at different rates, twenty-seven Fagri Kalan mango trees (15 years old) were carefully selected. The foliar application effect of MM and AA on vegetative growth, total chlorophyll, leaf chemical constituents, productivity, and the fruit quality of mango trees (cv. Fagri Kalan) was investigated. The findings revealed that the investigated growth measurements and leaf chemical contents, as well as the fruiting aspects and the fruit quality improved significantly due to the application of MM and AA. A higher application rate of the micronutrient mixture (2 g L-1) in combination with the highest amino acid concentration (2 mg L-1) was the most effective combination that increased the yield, total soluble solids (TSS), total sugars (TS), and total carbohydrates by 28.0%, 3.0%, 5.8% and 15.0%, respectively, relative to untreated plants. The relationship between such characteristics revealed a strong positive correlation (0.80-0.95), confirming the importance of these materials in increasing the yield and quality of mangoes. Thus, using doses of MM and AA as a foliar spray four times during each growing season is recommended under similar environmental conditions and horticulture practices used in the current experiment.

Comparative Metabolic Profiling in Pulp and Peel of Green and Red Pitayas (Hylocereus polyrhizus and Hylocereus undatus) Reveals Potential Valorization in the Pharmaceutical and Food Industries.

Pitaya (Hylocereus genus) is a popular plant with exotic and nutritious fruit, which has widespread uses as a source of nutrients and raw materials in the pharmaceutical industry. However, the potential of pitaya peel as a natural source of bioactive compounds has not yet fully been explored. Recent advances in metabolomics have paved the way for understanding and evaluating the presence of diverse sets of metabolites in different plant parts. This study is aimed at exploring the diversity of primary and secondary metabolites in two commercial varieties of pitaya, i.e., green pitaya (Hylocereus undatus) and red pitaya (Hylocereus polyrhizus). A total of 433 metabolites were identified using a widely targeted metabolomic approach and classified into nine known diverse classes of metabolites, including flavonoids, amino acids and its derivatives, alkaloids, tannins, phenolic acids, organic acids, nucleotides and derivatives, lipids, and lignans. Red pitaya peel and pulp showed relatively high accumulation of metabolites viz. alkaloids, amino acids and its derivatives, and lipids. Differential metabolite landscape of pitaya fruit indicated the presence of key bioactive compounds, i.e., L-tyrosine, L-valine, DL-norvaline, tryptophan, γ-linolenic acid, and isorhamnetin 3-O-neohesperidoside. The findings in this study provide new insight into the broad spectrum of bioactive compounds of red and green pitaya, emphasizing the valorization of the biowaste pitaya peel as raw material for the pharmaceutical and food industries.

Synthesis of zinc hydroxystannate/reduced graphene oxide composites using chitosan to improve poly(vinyl chloride) performance.

Chitosan-modified zinc hydroxystannate (ZHS-CS) was synthesized using the cations of the biomaterial chitosan (CS) and ion replacement strategy. A ZHS-CS and reduced graphene oxide (rGO) hybrid flame retardant (ZHS-CS/rGO) was synthesized for use in flexible poly (vinyl chloride) (PVC). Scanning electron microscopy images indicated that ZHS-CS and rGO were evenly dispersed in ZHS-CS/rGO without agglomeration. Fourier transform infrared spectroscopy results showed that rGO was fully reduced. The flame-retardant and mechanical properties of PVC composites were investigated using the limiting oxygen index (LOI), a cone calorimeter, and mechanical equipment. By replacing one-fifth of the zinc ions in ZHS by chitosan cations to obtain Sn-4Zn-1CS/rGO, the ZHS-CS/rGO was found to improve PVC composite performance. The total heat release and total smoke release of PVC/Sn-4Zn-1CS/rGO were reduced by 24.2 and 40.0 %, respectively, from those of pure PVC.

A vermicompost and deep tillage system to improve saline-sodic soil quality and wheat productivity.

Land degradation due to soil salinity and sodicity is a serious concern in arid ecosystems. Despite the importance of conservation tillage in carbon sequestration and improving soil properties, its effect on saline-sodic soils under amendment application remains unknown. Therefore, the present study aimed to explore the combined effects of inorganic (sulfuric acid and gypsum) and organic (vermicompost) soil amendments and tillage systems (zero, reduced and deep tillage) on saline-sodic soil properties and wheat productivity. Deep tillage with vermicompost application significantly improved soil physical and chemical properties compared with control. Interestingly, integration between deep tillage and vermicompost decreased soil salinity and sodicity by 37% and 34%, respectively, compared with zero tillage and unamended soils. The application of vermicompost surpassed chemical amendments in the improvement of saline-sodic soils and consequently increased the growth and yield of wheat, provided that deep tillage was used as a suitable tillage system. Although deep tillage reduced soil organic carbon, application of vermicompost not only compensated this reduction, but also significantly increased soil organic carbon. This confirms the potential of combined deep tillage and vermicompost as a method for environmentally reclaiming saline-sodic soils.

Combined Transcriptome and Metabolome analysis of Pitaya fruit unveiled the mechanisms underlying Peel and pulp color formation.

BACKGROUND: Elucidating the candidate genes and key metabolites responsible for pulp and peel coloration is essential for breeding pitaya fruit with new and improved appeal and high nutritional value. Here, we used transcriptome (RNA-Seq) and metabolome analysis (UPLC-MS/MS) to identify structural and regulatory genes and key metabolites associated with peel and pulp colors in three pitaya fruit types belonging to two different Hylocereus species. RESULT: Our combined transcriptome and metabolome analyses suggest that the main strategy for obtaining red color is to increase tyrosine content for downstream steps in the betalain pathway. The upregulation of CYP76ADs is proposed as the color-breaking step leading to red or colorless pulp under the regulation by WRKY44 transcription factor. Supported by the differential accumulation of anthocyanin metabolites in red pulped pitaya fruit, our results showed the regulation of anthocyanin biosynthesis pathway in addition to betalain biosynthesis. However, no color-breaking step for the development of anthocyanins in red pulp was observed and no biosynthesis of anthocyanins in white pulp was found. Together, we propose that red pitaya pulp color is under the strict regulation of CYP76ADs by WRKYs and the anthocyanin coexistence with betalains is unneglectable. We ruled out the possibility of yellow peel color formation due to anthocyanins because of no differential regulation of chalcone synthase genes between yellow and green and no detection of naringenin chalcone in the metabolome. Similarly, the no differential regulation of key genes in the carotenoid pathway controlling yellow pigments proposed that the carotenoid pathway is not involved in yellow peel color formation. CONCLUSIONS: Together, our results propose several candidate genes and metabolites controlling a single horticultural attribute i.e. color formation for further functional characterization. This study presents useful genomic resources and information for breeding pitaya fruit with commercially attractive peel and pulp colors. These findings will greatly complement the existing knowledge on the biosynthesis of natural pigments for their applications in food and health industry.

High-Performance Cyanate Ester Resins with Interpenetration Networks for 3D Printing.

As the 3D printing technology is getting more and more popular and useful, demands for materials for 3D printing have increased significantly. Cyanate ester (CE) resin possesses the characteristics of high heat distortion temperature and high glass transition temperature, outstanding mechanical properties, low dielectric constant, and excellent water uptake. However, CE resin has not been widely used in 3D printing of UV curing because it is difficult for photopolymerizable groups to graft onto the chains of CE resin. On the other hand, the glass transition temperature (Tg) of the homopolymer of the tris(2-hydroxyethyl)isocyanurate triacrylate (THEICTA) outclasses that of other acrylates. Although THEICTA is particularly advantageous to prepare a UV-curing prepolymer with high glass transition temperature, it also cannot be directly used for fabricating heat-resistant 3D-printed parts because it is solid and adding diluents will reduce the thermal stability of printed objects. This study is unique in producing 3D-printed materials, in which the THEICTA tactfully dissolves in low viscosity (about 100 mPa·s under 25 °C) bisphenol E cyanate (BECy) without sacrificing two kinds of bulk material properties. In the process of 3D printing, the carbon-carbon double bonds from THEICTA are cured by radical polymerization. Postprinting thermal treatment transforms three cyanate groups to a triazine ring structure. Additionally, the two kinds of structures are interpenetrating. The high-performance 3D-printing material has potential in fields ranging from space flight and aviation to the automotive and electronic industry.

The integrated effect of salinity, organic amendments, phosphorus fertilizers, and deficit irrigation on soil properties, phosphorus fractionation and wheat productivity.

Soil degradation due to global warming, water scarcity and diminishing natural resources negatively impacts food security. Soil fertility deterioration, particularly phosphorus (P) deficiency, remains a challenge in the arid and semi-arid regions. In this study, field experiments were conducted in different geographical locations to investigate the effects of organic amendments coupled with P fertilization and irrigation on soil physical-chemical properties, and the growth, yield and quality of wheat. Application of P fertilizers combined with organic amendments mitigated soil salinity, increased organic matter content, available water, hydraulic conductivity and available macronutrients, but decreased soil bulk density. Application of organic amendments slightly increased total Cd, Ni and Pb in soil, but Cd and Ni concentration was below allowable limits whilst Pb reached a hazardous level. Soil P fractions were significantly increased with the combined application of mineral P and organic amendments irrespective of salinity and irrigation. Crop growth yield and quality of wheat improved significantly in response to the integrated application of mineral P and organic amendments. In conclusion, the combination of mineral P sources with organic amendments could be successfully used as a cost-effective management practice to enhance soil fertility and crop production in the arid and semi-arid regions stressed with water scarcity and natural resource constraints.

Transcriptome Profiling Provides Insight into the Genes in Carotenoid Biosynthesis during the Mesocarp and Seed Developmental Stages of Avocado (Persea americana).

Avocado (Persea americana Mill.) is an economically important crop because of its high nutritional value. However, the absence of a sequenced avocado reference genome has hindered investigations of secondary metabolism. For next-generation high-throughput transcriptome sequencing, we obtained 365,615,152 and 348,623,402 clean reads as well as 109.13 and 104.10 Gb of sequencing data for avocado mesocarp and seed, respectively, during five developmental stages. High-quality reads were assembled into 100,837 unigenes with an average length of 847.40 bp (N50 = 1725 bp). Additionally, 16,903 differentially expressed genes (DEGs) were detected, 17 of which were related to carotenoid biosynthesis. The expression levels of most of these 17 DEGs were higher in the mesocarp than in the seed during five developmental stages. In this study, the avocado mesocarp and seed transcriptome were also sequenced using single-molecule long-read sequencing to acquired 25.79 and 17.67 Gb clean data, respectively. We identified 233,014 and 238,219 consensus isoforms in avocado mesocarp and seed, respectively. Furthermore, 104 and 59 isoforms were found to correspond to the putative 11 carotenoid biosynthetic-related genes in the avocado mesocarp and seed, respectively. The isoform numbers of 10 out of the putative 11 genes involved in the carotenoid biosynthetic pathway were higher in the mesocarp than those in the seed. Besides, alpha- and beta-carotene contents in the avocado mesocarp and seed during five developmental stages were also measured, and they were higher in the mesocarp than in the seed, which validated the results of transcriptome profiling. Gene expression changes and the associated variations in gene dosage could influence carotenoid biosynthesis. These results will help to further elucidate carotenoid biosynthesis in avocado.

Biochemical and Functional Characterization of Anthocyanidin Reductase (ANR) from Mangifera indica L.

Mango (Mangifera indica L.) is abundant in proanthocyanidins (PAs) that are important for human health and plant response to abiotic stresses. However, the molecular mechanisms involved in PA biosynthesis still need to be elucidated. Anthocyanidin reductase (ANR) catalyzes a key step in PA biosynthesis. In this study, three ANR cDNAs (MiANR1-1,1-2,1-3) were isolated from mango, and expressed in Escherichia coli. In vitro enzyme assay showed MiANR proteins convert cyanidin to their corresponding flavan-3-ols, such as (-)-catechin and (-)-epicatechin. Despite high amino acid similarity, the recombinant ANR proteins exhibited differences in enzyme kinetics and cosubstrate preference. MiANR1-2 and MiANR1-3 have the same optimum pH of 4.0 in citrate buffer, while the optimum pH for MiANR1-1 is pH 3.0 in phosphate buffer. MiANR1-1 does not use either NADPH or NADH as co-substrate while MiANR1-2/1-3 use only NADPH as co-substrate. MiANR1-2 has the highest Km and Vmax for cyanidin, followed by MiANR1-3 and MiANR1-1. The overexpression of MiANRs in ban mutant reconstructed the biosynthetic pathway of PAs in the seed coat. These data demonstrate MiANRs can form the ANR pathway, leading to the formation of two types of isomeric flavan-3-ols and PAs in mango.