Combination of a Deep Eutectic Solvent and Macroporous Resin for Green Recovery of Iridoids, Chlorogenic Acid, and Flavonoids from Eucommia ulmoides Leaves.

To increase the effectiveness of using typical biomass waste as a resource, iridoids, chlorogenic acid, and flavonoids from the waste biomass of Eucommia ulmoides leaves (EULs) were extracted by deep eutectic solvents (DESs) in conjunction with macroporous resin. To optimize the extract conditions, the experiment of response surface was employed with the single-factor of DES composition molar ratio, liquid-solid ratio, water percentage, extraction temperature, and extraction time. The findings demonstrated that the theoretical simulated extraction yield of chlorogenic acid (CGA), geniposidic acid (GPA), aucubin (AU), geniposide (GP), rutin (RU), and isoquercetin (IQU) were 42.8, 137.2, 156.7, 5.4, 13.5, and 12.8 mg/g, respectively, under optimal conditions (hydrogen bond donor-hydrogen bond acceptor molar ratio of 1.96, liquid-solid ratio of 28.89 mL/g, water percentage of 38.44%, temperature of 317.36 K, and time of 55.59 min). Then, 12 resins were evaluated for their adsorption and desorption capabilities for the target components, and the HPD950 resin was found to operate at its optimum. Additionally, the HPD950 resin demonstrated significant sustainability and considerable potential in the recyclability test. Finally, the hypoglycemic in vitro, hypolipidemic in vitro, immunomodulatory, and anti-inflammatory effects of EUL extract were evaluated, and the correlation analysis of six active components with biological activity and physicochemical characteristics of DESs by heatmap were discussed. The findings of this study can offer a theoretical foundation for the extraction of valuable components by DESs from waste biomass, as well as specific utility benefits for the creation and development of natural products.

Extraction and Purification of Aucubin from Eucommia ulmoides Seed Draff in Natural Deep Eutectic Solvents Using Macroporous Resins.

Aucubin (AU) is an active ingredient that exerts strong antioxidant and anti-inflammatory effects in the treatment of several diseases. In order to improve the efficiency of resource utilization of traditional biomass waste, Eucommia ulmoides seed-draff (EUSD) waste biomass was used as the raw material, and a series of deep eutectic solvents were selected to evaluate the extraction efficiency of aucubin from EUSD. A response surface experiment was designed based on a single-factor experiment to optimize the extract conditions. The results showed that the best conditions for aucubin extraction were an HBD-HBA ratio of 2.18, a liquid-solid ratio of 46.92 mL/g, a water percentage of 37.95%, a temperature of 321.03 K, and an extraction time of 59.55 min. The maximum amount of aucubin was 156.4 mg/g, which was consistent with the theoretical value (156.8 mg/g). Then, the performance of 12 resins for adsorption and desorption was contrasted. The results revealed that HPD950 resin exhibited the best performance, with an adsorption capacity of 95.2% and a desorption capacity of 94.3%. Additionally, the pseudo-second-order model provided the best match to the kinetics data, the Langmuir model provided the best fit to the isotherm data, and adsorption was a beneficial, spontaneous, exothermic, and physical process. In the recyclability test, the HPD950 resin had great potential and excellent sustainability in aucubin recovery. In the antioxidant activity study, the aucubin extract exerted a strong antioxidant ability with scavenging capabilities for four free radicals. Furthermore, the antifungal activity study found that the aucubin extract exhibited a good antifungal effect against 5 tested pathogens. The research results can provide a theoretical basis for the extraction of high-value components from waste biomass by deep eutectic solvent and a certain application value for the development and utilization of natural aucubin products.

Giant Cavity Macrocycle: Synthesis, Structure, and Its Complexation with Pagoda[5]arene.

A novel stretched hexagon structure naphthalene diimides-extended-pillar[6]arene 1 with a giant cavity size of 18.769 Å in width and 17.109 Å in height is reported. 1 exhibits highly selective binding of pagoda[5]arene compared to pillar[5]arene and prism[5]arene. Size matching and charge transfer interactions play a key role in the formation of the ring-in-ring stable complex.

Recent advances in peptide-based therapeutic strategies for breast cancer treatment.

Breast cancer is the leading cause of cancer-related fatalities in female worldwide. Effective therapies with low side effects for breast cancer treatment and prevention are, accordingly, urgently required. Targeting anticancer materials, breast cancer vaccines and anticancer drugs have been studied for many years to decrease side effects, prevent breast cancer and suppress tumors, respectively. There are abundant evidences to demonstrate that peptide-based therapeutic strategies, coupling of good safety and adaptive functionalities are promising for breast cancer therapy. In recent years, peptide-based vectors have been paid attention in targeting breast cancer due to their specific binding to corresponding receptors overexpressed in cell. To overcome the low internalization, cell penetrating peptides (CPPs) could be selected to increase the penetration due to the electrostatic and hydrophobic interactions between CPPs and cell membranes. Peptide-based vaccines are at the forefront of medical development and presently, 13 types of main peptide vaccines for breast cancer are being studied on phase III, phase II, phase I/II and phase I clinical trials. In addition, peptide-based vaccines including delivery vectors and adjuvants have been implemented. Many peptides have recently been used in clinical treatments for breast cancer. These peptides show different anticancer mechanisms and some novel peptides could reverse the resistance of breast cancer to susceptibility. In this review, we will focus on current studies of peptide-based targeting vectors, CPPs, peptide-based vaccines and anticancer peptides for breast cancer therapy and prevention.

Kaolin-loaded carboxymethyl chitosan/sodium alginate composite sponges for rapid hemostasis.

There are several factors that contribute to the mortality of people who suffer from unmanageable bleeding. Therefore, the development of rapid hemostatic materials is necessary. Herein, novel rapid hemostatic composite sponges were developed by incorporation of kaolin (K) into carboxymethyl chitosan (CMCS)/sodium alginate (SA) via a combination of methods that includes ionic crosslinking, polyelectrolyte action, and freeze-drying. The CMCS/SA-K composite sponges were cross-linked with calcium ions provided by a sustained-release system consisting of D-gluconolactone (GDL) and Ca-EDTA, and the hemostatic ability of the sponges was enhanced by loading the inorganic hemostatic agent-kaolin (K). It was demonstrated that the CMCS/SA-K composite sponges had a good porous structure and water absorption properties, excellent mechanical properties, outstanding biodegradability, and biocompatibility. Simultaneously, they exhibited rapid hemostatic properties, both in vitro and in vivo. Significantly, the hemostatic time of the CMCS/SA-K60 sponge was improved by 82.76 %, 191.82 %, and 153.05 %, compared with those of commercially available gelatin sponges in the rat tail amputation, femoral vein, and liver injury hemorrhage models respectively, indicating that its hemostatic ability was superior to that of commercially available hemostatic materials. Therefore, CMCS/SA-K composite sponges show great promise for rapid hemostasis.

Hydrogel Complex Containing the Antimicrobial Peptide HX-12C Accelerates Healing of Infected Wounds.

Bacterial infections of the wound surface can be painful for patients, and traditional dressings do not effectively address this problem. In this study, an antimicrobial wound dressing is prepared using a novel antimicrobial peptide, HX-12C. This hydrogel system is based on the natural biomaterials sodium alginate and gelatin, utilizing calcium carbonate as a source of Ca2+ , and ionic cross-linking is facilitated by lowering the solution pH. The resulting sodium alginate/gelatin HX-12C-loaded hydrogel (CaAGEAM) has good mechanical and adhesion properties, biocompatibility and in vitro degradability. Its extraordinary antibacterial efficacy (>98%) is verified by an antibacterial experiment. More importantly, in vivo experiments further demonstrate its healing-promotion effect, with a 95% wound healing rate by day 9. Tissue staining demonstrates that the hydrogel containing antimicrobial peptides is effective in suppressing inflammation. The dressing promotes wound healing by stimulating the deposition of skin appendages and collagen. The results of this study suggest that composite hydrogels containing antimicrobial peptides are a promising new type of dressing to promote the healing of infected wounds.

Chitosan-based packaging films with an integrated antimicrobial peptide: Characterization, in vitro release and application to fresh pork preservation.

Chitosan (CS) films were developed incorporating peptide HX-12C. The films were studied to determine their microstructures, physical properties, release properties of peptide HX-12C and functional properties. The results indicated that there may be hydrogen bonding interactions between CS and peptide HX-12C, thereby creating a homogeneous internal microstructure and lower crystallinity (10.8-12.8 %). Compared with CS film, CS-HX-12C films displayed lower light transmission, MC (20.8-19.9 %), WVP (8.82-8.59 × 10-11·g·m-1·s-1·Pa-1), OTR (0.015-0.037 cc/(m2.day)) and higher WS (15.7-32.4 %) values. Moreover, controlled-release experiments showed that pH, ionic strength and temperature could all significantly affect the release of peptide HX-12C from the films. Finally, the increase of pH value and TVC and lipid oxidation of fresh pork were delayed due to the treatment with CS-2%HX-12C film. However, incorporating peptide HX-12C into CS films did not improve the mechanical properties of the films and their effects against protein oxidation. Our results suggest that the CS-based antimicrobial packaging films integrated with peptide HX-12C exhibit the potential for fresh pork preservation.

Advancements, challenges and future perspectives on peptide-based drugs: Focus on antimicrobial peptides.

Among other health related issues, the rising concerns on drug resistance led to look for alternative pharmaceutical drugs that are effective both against infectious and noninfectious diseases. Antimicrobial peptides (AMPs) emerged as potential therapeutic molecule with wide range of applications. With their limitations, AMPs have gained reputable attentions in research as well as in the pharmaceutical industry. This review highlighted the historical background, research trends, technological advancements, challenges, and future perspectives in the development and applications of peptide drugs. Some vital questions related with the need for pharmaceutical production, factors for the slow and steady journey, the importance of oral bioavailability, and the drug resistance possibilities of AMPs were raised and addressed accordingly. Therefore, the current study is believed to provide a profound understanding in the past and current scenarios and future directions on the therapeutic impacts of peptide drugs.

Fabrication and application of chitosan-based biomass composites with fire safety, water treatment and antibacterial properties.

In this work, a biomass composite material (CS@NC@PA-Na) was prepared from chitosan (CS), nano-cellulose (NC) and sodium phytate (PA-Na). The prepared products were characterized by scanning electron microscopy (SEM), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectrometry (XPS) and X-ray diffraction (XRD). The fire/water safety and antimicrobial properties of the CS@NC@PA-Na were fully studied. The results indicated CS@NC@PA-Na (50 mg) could effectively reduce the concentration of methyl orange by 85 % under 30 min adsorption. Meanwhile, only 5 wt% CS@NC@PA-Na could increase the limiting oxygen index (LOI) value of epoxy resin composite from 24.5 to 30.1 %, and decrease the peak heat/smoke release rate by 29.5 and 33.3 %, respectively. Moreover, CS@NC@PA-Na also exhibited excellent antibacterial effect. This work provides an efficient, feasible and eco-friendly route for large-scale production of multi-functional CS-based biomass materials that could be used in the fields of fire safety and environmental conservation.

Study on extraction and antibacterial activity of aucubin from Eucommia ulmoides seed-draff waste biomass.

Aucubin (AU) is an active ingredient exerting strong antioxidant and anti-inflammatory effects in treating several diseases. This study evaluated the extraction of AU from Eucommia ulmoides seed-draff (EUSD) waste biomass using a series of solvents (methanol, ethanol, i-propanol, n-propanol, n-butanol, n-pentanol and cyclohexane) assisted with microwave and ultrasound, and proposed the optimized method for extraction. Five factors were investigated by Box-Behnken design (BBD) and response surface methodology (RSM). The optimized extraction conditions were as follows: liquid-solid ratio of 46.37 mL/g, methanol percentage of 89.56%, ultrasonic (extraction) time of 59.95 min, microwave power of 306.73 W, and microwave (extraction) time of 18.93 s. To this end, the AU extraction reached the maximum value (149.1 mg/g), which was consistent with the theoretical value (149.3 mg/g). Furthermore, the kinetics of extraction process were investigated by mathematic modeling. The extraction process analysis was also explored by 1H nuclear magnetic resonance (1H-NMR) spectroscopy, Fourier transform infrared (FTIR) spectroscopy and COSMOtherm program. This study found out that methanol provided better extraction efficiency than the conventional solvents (water, ethanol, i-propanol, n-propanol, n-butanol, n-pentanol, cyclohexane) due to possible interactions by the formation of hydrogen bond between AU and methanol, and ultrasound and microwave could significantly enhance mass transfer, which exhibited higher extraction efficiency and lower energy consumptions (149.1 mg/g and 0.102 kW·h vs. 73.4 mg/g and 0.700 kW·h for Soxhlet extraction). In the antibacterial activity study, the AU extract exerted strong antibacterial ability against 4 tested pathogens, and the antibacterial effect followed the order of: Staphylococcus aureus (35.9 ± 1.32 mm) > Escherichia coli (30.7 ± 1.38 mm) > Bacillus subtilis (20.5 ± 1.36 mm) > Salmonella (15.9 ± 1.39 mm) with the AU concentration of 40 mg/mL. Therefore, the development of this study will help to deepen the further understanding of natural product extraction by methanol-based ultrasonic and microwave, and has certain application value for the development and utilization of natural iridoid glycosides product.

Visible-light-promoted trifluoromethylselenolation of ortho-hydroxyarylenaminones.

Development of an efficient process that employs easy to handle and shelf-stable reagents for the synthesis of trifluoromethylselenylated heterocyclics remains a daunting challenge in organic synthesis. Herein, we report a green and practical protocol using trifluoromethyl tolueneselenosulfonate and ortho-hydroxyarylenaminones to access a wide range of chromone derivatives under photocatalyst and oxidant free conditions. This reaction proceeded smoothly under photoirradiation conditions and various functional groups were tolerant of the reaction conditions.

Two phenanthroimidazole turn-on probes for the rapid detection of selenocysteine and its application in living cells imaging.

Detection of selenocysteine (Sec) content in cells by fluorescence probe is of great significance for the identification of human related diseases. To achieve fast and sensitive detection of Sec, two isomers A4 and B4 as turn-on fluorescent probes to detect Sec were designed and synthesized. Both A4 and B4 display fast turn-on response, high selectivity and sensitivity toward Sec, which can be applied for fluorescence imaging of Sec in living cells. Compared with B4, A4 has a larger Stokes shift (125 nm), wider pH range (5-10) and lower detection limit (65.4 nM) due to its ESIPT (excited state intramolecular proton transfer) effect. In view of the detection performance of these two probes, they can be used as effective tools for detecting Sec in biological systems.

A FRET-ICT Dual-Modulated Ratiometric Fluorescence Sensor for Monitoring and Bio-Imaging of Cellular Selenocysteine.

Since the fluctuation of cellular selenocysteine (Sec) concentration plays an all-important role in the development of numerous human disorders, the real-time fluorescence detection of Sec in living systems has attracted plenty of interest during the past decade. In order to obtain a faster and more sensitive small organic molecule fluorescence sensor for the Sec detection, a new ratiometric fluorescence sensor Q7 was designed based on the fluorescence resonance energy transfer (FRET) strategy with coumarin fluorophore as energy donor and 4-hydroxy naphthalimide fluorophore (with 2,4-dinitrobenzene sulfonate as fluorescence signal quencher and Sec-selective recognition site) as an energy acceptor. The sensor Q7 exhibited only a blue fluorescence signal, and displayed two well distinguished emission bands (blue and green) in the presence of Sec with ∆λ of 68 nm. Moreover, concentrations ranging of quantitative detection of Sec of Q7 was from 0 to 45 µM (limit of detection = 6.9 nM), with rapid ratiometric response, high sensitivity and selectivity capability. Impressively, the results of the living cell imaging test demonstrated Q7 has the potentiality of being an ideal sensor for real-time Sec detection in biosystems.

Antimicrobial Peptide Reverses ABCB1-Mediated Chemotherapeutic Drug Resistance.

Multidrug resistance (MDR) of tumor cells to chemotherapeutic agents is the main reason for the failure of cancer chemotherapy. Overexpression of ABCB1 transporter that actively pumps various drugs out of the cells has been considered a major contributing factor for MDR. Over the past decade, many antimicrobial peptides with antitumor activity have been identified or synthesized, and some antitumor peptides have entered the clinical practice. In this study, we report that peptide HX-12C has the effect of reversing ABCB1-mediated chemotherapy resistance. In ABCB1-overexpressing cells, nontoxic dose of peptide HX-12C inhibited drug resistance and increased the effective intracellular concentration of paclitaxel and other ABCB1 substrate drugs. The mechanism study showed that peptide HX-12C stimulated ABCB1 ATPase activity without changing the expression level and localization patterns of ABCB1. Molecular docking predicted the binding modes between peptide HX-12C and ABCB1. Overall, we found that peptide HX-12C reverses ABCB1-mediated MDR through interacting with ABCB1 and blocking its function without affecting the transporter's expression and cellular localization. Our findings suggest that this antimicrobial peptide may be used as a novel prospective cancer therapeutic strategy in combination with conventional anticancer agents.

A Red Emissive Fluorescent Turn-on Sensor for the Rapid Detection of Selenocysteine and Its Application in Living Cells Imaging.

The content of selenocysteine in cells has an important effect on a variety of human diseases, and the detection of selenocysteine by fluorescent sensors in vivo has shown many advantages. In order to further develop fast-reaction-time, good-selectivity, and high-sensitivity long-wavelength selenocysteine fluorescent sensors, we designed and synthesized the compound YZ-A4 as a turn-on fluorescent sensor to detect the content of selenocysteine. The quantitative detection range of the sensor YZ-A4 to selenocysteine was from 0 to 32 µM, and the detection limit was as low as 11.2 nM. The sensor displayed a rapid turn-on response, good selectivity, and high sensitivity to selenocysteine. Finally, we have demonstrated that YZ-A4 could be used for fluorescence imaging of selenocysteine in living cells.

Current advances on waste biomass transformation into value-added products.

Ceaseless growth in human population led to high demand in everything. Currently, the world largely depends on petroleum-based "all material synthesis" scheme. On the other hand, depletion of fossil-based resources and their huge impact on environmental pollution have forced us to search for sustainable and eco-friendly alternative resources. In this context, the notion to utilize waste biomass could possibly provide environmental and economic benefits. This study was carefully designed to critically review state of the art in the transformation of waste biomass into value-added products. Even though extensive reviews on biomass utilization have been published in the past few years, the current study basically focused on new trends and prospective in this area. Here, global biomass potential, research developments and practices, novel biomass transformation approaches, and future perspectives were broadly discussed. More importantly, in addition to revising published researches, already implemented and ongoing large-scale projects on valorization of waste biomass have been assessed. Therefore, this study is believed to give crucial information on the current status and future direction of waste biomass utilization so as to accomplish the quest towards green economy.Key Points • Huge biomass potential and dramatically increase in R&D trends on waste biomass.• Selection of appropriate waste biomass valorization techniques. • Development of efficient and feasible waste biomass transformation technology. • Coproduction of low-value, high-volume and high-value, low volume products.

Opportunities, challenges, and future perspectives of succinic acid production by Actinobacillus succinogenes.

Due to environmental issues and the depletion of fossil-based resources, ecofriendly sustainable biomass-based chemical production has been given more attention recently. Succinic acid (SA) is one of the top value added bio-based chemicals. It can be synthesized through microbial fermentation using various waste steam bioresources. Production of chemicals from waste streams has dual function as it alleviates environmental concerns; they could have caused because of their improper disposal and transform them into valuable products. To date, Actinobacillus succinogenes is termed as the best natural SA producer. However, few reviews regarding SA production by A. succinogenes were reported. Herewith, pathways and metabolic engineering strategies, biomass pretreatment and utilization, and process optimization related with SA fermentation by A. succinogenes were discussed in detail. In general, this review covered vital information including merits, achievements, progresses, challenges, and future perspectives in SA production using A. succinogenes. Therefore, it is believed that this review will provide platform to understand the potential of the strain and tackle existing hurdles so as to develop superior strain for industrial applications. It will also be used as a baseline for identification, isolation, and improvement of other SA-producing microbes.

Bio-succinic acid production from coffee husk treated with thermochemical and fungal hydrolysis.

Coffee husk (CH), a waste obtained from processing of coffee cherries via dry method, causes serious environmental problems. In this study, strategies were designed to utilize CH for succinic acid (SA) production. Three different CH hydrolysis methods: thermal, thermochemical and crude enzymes obtained by solid state fermentation of Aspergillus niger and Trichoderma reesei, were evaluated to generate fermentable feedstock for SA production using Actinobacillus succinogenes. The feasibility of these pretreatment methods was investigated. Accordingly, thermochemical hydrolysis using H2SO4 at 121 °C for 30 min, appeared the most effective method for CH hydrolysis, producing 24.4 g/L of reducing sugars (RS). Finally, 19.3 g/L of SA with yield and productivity of 0.95 g SA/g RS and 0.54 g/L/h, respectively, were obtained using CH hydrolysate. The current study revealed an alternative way of utilization coffee waste for value addition while mitigating environmental problems caused by its disposal.

Succinic acid production from fruit and vegetable wastes hydrolyzed by on-site enzyme mixtures through solid state fermentation.

In this study, a novel biorefinery concept of succinic acid (SA) production from fruit and vegetable wastes (FVWs) hydrolyzed by crude enzyme mixtures through solid state fermentation was designed. Enzyme complex solid mashes from various types of FVWs were on-site produced through solid-state fermentation by Aspergillus niger and Rhizopus oryzae. This solid was then added to FVW suspensions and undergo hydrolysis reaction to generate fermentable sugars and other essential nutrients for bacterial growth and product formation. The subsequent fungal hydrolysis produced 12.00g/L glucose and 13.83g/L fructose using 10% mass ratio (w/v) of FVW. Actinobacillus succinogenes used this FVW hydrolysate as the sole feedstock and produced 27.03g/L of succinic acid with high yield and productivity of 1.18gSA/g sugar and 1.28gL-1h-1, respectively. This work demonstrated that FVWs can be biotransformed to value added products which have considerable potential economics and environmental meaning.