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In vivo and in vitro studies reveal that Ursolic Acid (UA) is able to counteract endogenous and exogenous inflammatory stimuli and has favorable anti-inflammatory effects. The antiinflammatory mechanisms mainly include decreasing the release of histamine in mast cells, suppressing the activities of lipoxygenase, cyclooxygenase and phospholipase, and reducing the production of nitric oxide and reactive oxygen species, blocking the activation of the signal pathway, downregulating the expression of inflammatory factors, and inhibiting the activities of elastase and complement. These mechanisms can open up new avenues for the scientific community to develop or improve novel therapeutic approaches to tackle inflammatory diseases, such as arthritis, atherosclerosis, neuroinflammation, liver diseases, kidney diseases, diabetes, dermatitis, bowel diseases, cancer. The anti-inflammatory activity, the anti-inflammatory mechanism of ursolic acid and its therapeutic applications are reviewed in this paper.

Oleanolic acid can inhibit edema and exhibit obvious inhibitory activity to inflammatory by activating of the pituitary-adrenal cortical system, inhibiting the synthesis or release of PGs, inhibiting endotoxin-mediated release of HMGB1 by endothelial cells or regulating MAPK, PI3K/Akt/NF- κB/ICAM-1/JAK/STAT signaling pathways, etc. In recent years, an increased number of interesting research work has been carried out on the anti-inflammatory activity and mechanisms of OA derivatives, such as acyloxyimino derivative, 3-acetylated derivatives, novel 3,5-disubstituted isoxazoles derivatives, acetate, ester derivatives and oximes derivatives. The review summaries and highlights the updated advances on the anti-inflammatory activity and mechanism of OA and its derivatives.

By studying the expression in patients and cell modeling in vitro, antimicrobial peptides for Klebsiella were screened. Killing curve and membrane permeability experiments are used to study the antibacterial effect of antimicrobial peptides in vitro. Cytotoxicity related indicators including lipopolysaccharide (LPS), Capsule polysaccharide (CPS) and outer membrane protein expression were measured. Intranasal inoculation of Pneumoconiosis was used to construct a mouse infection model, and the survival rate and cytokine expression level were tested. Human Neutrophil Peptide 1 (HNP-1) showed significant antibacterial effect, which improved the permeability of the outer membrane of K. pneumoniae. Moreover, HNP-1 decreased LPS, CPS content and outer membrane proteins. K. pneumoniae infection decreased antimicrobial peptide, oxidative stress and autophagy-related genes, while HNP-1 increased these genes. After co-culture with macrophages, the endocytosis of macrophages is enhanced and the bacterial load is greater in K. pneumoniae + peptide group. Besides, higher levels of pp38 and pp65 in K. pneumoniae + peptide group. HNP-1 rescued the cytotoxicity induced by K. pneumoniae. Survival rate is significantly improved after K. pneumoniae treated by HNP-1. All cytokines in the peptide group were significantly higher. HNP-1 promotes immune sterilization by reducing the virulence of multidrug-resistant K. pneumoniae and increasing the ability of macrophages. This article is protected by copyright. All rights reserved.

A new acceptor, benzoylphenyltriazine, was explored as a strong acceptor of thermally-activated delayed-fluorescent (TADF) emitters because of its high external quantum efficiency. The benzoylphenyltriazine acceptor was designed to have strong acceptor strength by modifying a well-known phenyltriazine acceptor with a weak electron-withdrawing benzoyl unit. The extra benzoyl unit strengthened the electron-accepting strength of the phenyltriazine acceptor, which improved the light emission performances of the TADF emitters. A BTrztCz molecule is a derivative of the benzoylphenyltriazine acceptor and was studied as a TADF emitter. The comparison of the BTrztCz emitter with a TrztCz emitter, derived from phenyltriazine based on the same donor, showed that benzoylphenyltriazine acceptor is superior to phenyltriazine for delayed-fluorescence characteristics. The quantum efficiency of the BTrztCz (21.4%) device is greater than that of the TrztCz (20.6%) device.

Autophagy, the process of lysosomal degradation of biological materials within cells, is often halted abnormally in proteopathies, such as tauopathy and amyloidopathy. Thus, autophagy regulators that rescue dysregulated autophagy have great potential to treat proteopathies. We previously reported that the natural small molecule kaempferide (Kaem) induces autophagy without perturbing mTOR signaling. Here, we report that Kaem promotes lysosomal degradation of microtubule-associated protein tau (MAPT) in inducible MAPT cells. Kaem enhanced autophagy flux by mitigating microtubule-associated protein 1 light chain 3 (LC3) accumulation when MAPT expression was induced. Kaem also promoted activation of transcription factor EB (TFEB) without inhibiting mTOR and without mTOR inhibition-mediated cytotoxicity. In addition, Kaem-induced MAPT degradation was abolished in the absence of mitochondrial elongation factor Tu (TUFM), which was previously shown to be a direct binding partner of Kaem. Collectively, these results demonstrate that Kaem could be a potential therapeutic for tauopathy and reveal that TUFM can be a drug target for autophagy-driven disorders.

Chlorpyrifos is an extensively used insecticide in the agriculture worldwide and was often detected in both surface waters and groundwater, posing threats to local residents’ health. Temporal chang...

A thermally activated delayed fluorescence (TADF)-type exciplex host employing a novel electron-transport type (n-type) type host managing positive polarons and stabilizing excitons was developed to elongate the device lifetime of deep blue phosphorescent organic light-emitting diodes (PhOLEDs). The bipolar n-type host was designed to prevent hole leakage and secure hole stability while being stabilized under excitons by introducing a CN-modified carbazole moiety as a weak donor. The TADF-type exciplex host-based blue PhOLEDs showed high (above 20 %) quantum efficiency with a deep blue color coordinate of (0.14, 0.16) and elongated device lifetime. The device operational lifetime of the blue PhOLEDs bearing the TADF-type exciplex host was extended by more than twice compared to that of the exciplex-free unipolar host. This work suggested a design concept of the n-type host to develop the TADF-type exciplex host for deep blue phosphors to reach a long lifespan in the deep blue PhOLEDs.

Fusidane-type antibiotics, represented by helvolic acid, fusidic acid and cephalosporin P1, are fungi-derived antimicrobials with little cross-resistance to commonly used antibiotics. Generation of new fusidane-type derivatives is therefore of great value, but this is hindered by available approaches. Here, we developed a stochastic combinational strategy by random assembly of all the post-tailoring genes derived from helvolic acid, fusidic acid, and cephalosporin P1 biosynthetic pathways in a strain that produces their common intermediate. Among a total of 27 gene combinations, 24 combinations produce expected products and afford 58 fusidane-type analogues, of which 54 are new compounds. Moreover, random gene combination can induce unexpected activity of some post-tailoring enzymes, leading to a further increase in chemical diversity. These newly generated derivatives provide new insights into the structure‒activity relationship of fusidane-type antibiotics. The stochastic combinational strategy established in this study proves to be a powerful approach for expanding structural diversity of natural products., Graphical abstract Chemical diversification of fusidane-type antibiotics was accomplished using a stochastic combinational strategy through random assembly of all the post-tailoring genes derived from helvolic acid, fusidic acid and cephalosporin P1 pathways.Image 1

Desmoplasia in the extracellular matrix (ECM) is one of the hallmarks of pancreatic cancer (PC), a virtually incurable disease. Decorin, a classical small leucine-rich proteoglycan found in the ECM, was upregulated in PC tissue samples according to the data of TCGA. However, decorin plays a protective role in the ECM. So it is necessary to study the roles of decorin in the progression of PC. A significantly upregulated expression of decorin was observed in the PC tissue samples compared with the normal tissues. However, there was no considerable difference in the level of expression of decorin during different pathological stages, which was supported by the immunoblot analysis. Western blot showed a higher expression of decorin A in the para-carcinoma tissue than in the cancerous tissue but the expression of decorin B, C, and D was elevated in the cancerous tissue. The results of the MTT and scratch wound healing assays revealed an elevated proliferation ability and migration rate in decorin B-overexpressing cells but were inhibited in the decorin A-overexpressing cells. Overexpression of decorin A significantly elevated the expression of the apoptosis-related genes and Decorin B-overexpression elevated proliferation-related genes. All the results showed that decorin B played important roles in the promoting of PC.

A simple wet-chemical route for the preparation of core-shell-structured catalysts was developed to achieve high oxygen reduction reaction (ORR) activity with a low Pt loading amount. Nickel nitride (Ni3N) nanoparticles were used as earth-abundant metal-based cores to support thin Pt layers. To realize the site-selective formation of Pt layers on the Ni3N core, hydrogen molecules (H2) were used as a mild reducing agent. As H2 oxidation is catalyzed by the surface of Ni3N, the redox reaction between H2 and Pt(IV) in solution was facilitated on the Ni3N surface, which resulted in the selective deposition of Pt on Ni3N. The controlled Pt formation led to a subnanometer (0.5-1 nm)-thick Pt shell on the Ni3N core. By adopting the core-shell structure, higher ORR activity than the commercial Pt/C was achieved. Electrochemical measurements showed that the thin Pt layer on Ni3N nanoparticle exhibits 5 times higher mass activity and specific activity than that of commercial Pt/C. Furthermore, it is expected that the proposed simple wet-chemical method can be utilized to prepare various transition-metal-based core-shell nanocatalysts for a wide range of energy conversion reactions.

Maslinic acid, a pentacyclic triterpene acid, is mainly isolated from olives. Maslinic acid and its derivatives exhibit a broad range of biological properties, such as anti-inflammatory, anticancer, anti-diabetic, antimicrobial, neuroprotective and hepatoprotective activities. In this minireview, the progress of research on maslinic acid with regard to its bioactivities, extraction, semisynthetic preparation and patents is reported. The relationships between the structure and the activity of maslinic acid and its derivatives are also discussed.

A novel electroplex host with two triplet exciton up-converting channels for suppressed triplet exciton triggered degradation mechanisms was developed using an electron transport type host (n-type host) with thermally activated delayed fluorescence (TADF) characteristics to improve the device lifetime of deep blue phosphorescent organic light-emitting diodes (PhOLEDs). The TADF-natured n-type host with high triplet energy was derived from triazine with benzonitrile and carbazole units to induce the TADF characteristics. The TADF natured n-type host generated an electroplex with a hole transport type host and the electroplex-based PhOLEDs revealed an extended device lifetime by more than twice compared to the non-TADF natured n-type host based electroplex host. Transient photoluminescence and electroluminescence analyses revealed that two reverse intersystem crossing (RISC) mechanisms through the n-type TADF host and electroplex host could suppress triplet exciton related degradation and improved the device lifetime. Kinetic modeling of the electroplex supported the RISC mechanisms of the electroplex.

Background: The focus of this study was to prepare and characterize the single-chain variable fragment antibody (scFv)-coupled immunoaffinity column for purification of subtilisin BRC. Methods: The scFv against subtilisin BRC was immobilized onto CNBr-activated Sepharose 4B. Adsorption isotherm for subtilisin BRC on scFv-BRC-coupled Sepharose 4B was obtained and calculated the maximum binding capacity. The extraction conditions, including eluting solution, the concentration of eluting solution and flow rate, were optimized. Under the optimized eluting conditions, the dynamic binding capacity of the immunoaffinity column was determined. Results: The scFv-BRC-coupled Sepharose 4B for immunoaffinity purification of subtilisin BRC was prepared. The coupling efficiency was about 78.4%, e.g. about 8 mg of scFv-BRC was covalently coupled to 1 g CNBr-activated Sepharose 4B. The maximum equilibrium binding capacity (qm) and dissociation constant (Kd) of the immunoaffinity column for subtilisin BRC were 3.01 mg/mL and 0.465 mg/mL, respectively. The immunoaffinity chromatography conditions were optimized and the subtilisin BRC was purified 3.29-fold with 55.6%. Conclusion: The subtilisin BRC was effectively purified with high purity using scFv-BRC-coupled Sepharose 4B and the dynamic binding capacity of the column was determined. These results suggested that scFv-BRC can be used as a ligand for affinity purification of subtilisin BRC.

Ginseng is a traditional medicine with a complex chemical composition, wide bioactivity and unique pharmacological action. Many studies have confirmed that ginsenosides are the active ingredients of ginseng, and ginsenosides have always been the focus of different researchers. With the development of modern separation and analysis technology, more than 150 kinds of ginsenosides have been isolated. The ginsenosides Rb1, Rb2, Rc, Rg1 and Re account for more than 80% of total ginsenosides, and other saponins, such as Rd, Rg3 and Rh2, which are minor constituents, accounting for only a small portion of the total amount. In recent years, ginsenosides have been found to possess strong pharmacological activities, such as antioxidation, clearing of oxygen free radicals, reducing calcium overload and anti-apoptosis. Ginsenosides play a protective role in ischemia-reperfusion injury. This paper reviews the protective effects of ginsenosides on myocardial ischemia and ischemiareperfusion injury.

C30H46O3·1/6H2O, monoclinic, C2 (no. 5), a = 29.4307(4) Å, b = 15.42797(17) Å, c = 18.4667(2) Å, β = 104.4652(12)°, V = 8119.11(17) Å3, Z = 12, R gt(F) = 0.0432, wR ref(F 2) = 0.1197, T = 293(2) K. CCDC no.: 2016692

C30H48O4, orthorhombic, P212121 (no. 19), a = 12.34133(14) Å, b = 16.50759(15) Å, c = 26.8804(2) Å, V = 5476.23(9) Å3, Z = 8, R gt(F) = 0.0422, wR ref(F 2) = 0.0990, T = 293 K.

C30H48O5, orthorhombic, P212121 (no. 19), a = 11.6608(10) Å, b = 14.8098(15) Å, c = 15.9975(16) Å, V = 2762.7(5) Å3, Z = 4, Rgt (F) = 0.0586, wRref (F 2) = 0.1580, T = 293(2) K.

C32H54O4, monoclinic, P21 (no. 4), a = 7.8727(1) Å, b = 19.9173(2) Å, c = 19.1801(2) Å, β = 94.539(1)°, V = 2998.06(6) Å3, Z = 4, R gt (F) = 0.0370, wR ref (F 2) = 0.0983, T = 293 K.

A selenium-catalyzed trifluoromethylthiolation/[2,3]-sigmatropic rearrangement of tertiary allylic and propargylic alcohols which could provide straightforward and facile access to trifluoromethyl sulfoxides was developed. Various allylic and allenic trifluoromethyl sulfoxides were obtained with moderate to excellent yields. Meanwhile, a Lewis acid mediated trifluoromethylthiolation/1,2-rearrangement to synthesize β-SCF3 carbonyl compounds was also accomplished. These two tandem reactions feature with mild reaction conditions and metal-free. During these two reactions, the chemoselectivity of electrophilic trifluoromethylthiolation was revealed.

ETHNOPHARMACOLOGICAL RELEVANCE Gentiana delavayi Franch. (Gentianaceae) as an ethnomedicinal plant contains a variety of effective active ingredients and exhibits diverse pharmacological actions, such as hepatoprotective, anti-inflammatory and central nervous system effects. In this study we investigated the influence of G. delavayi flower extract on amyloid precursor protein (APP) processing at molecular and cellular levels. APP/PS1 Chinese hamster ovary (CHO) cells were treated with chloroform extract of G. delavayi flower in different concentrations for 24 h. Concentrations of amyloid β (Aβ) 40 and Aβ42 in the cell supernatant and activity of β-site amyloid precursor protein cleaving enzyme 1 (BACE1), BACE2, and cathepsin D were determined. The expression of APP and neprilysin (NEP) within the cell were further determined. Compared with the control group, the levels of Aβ40 and Aβ42 declined notably and the activity of BACE1 was inhibited significantly in the APP/PS1 CHO cells after treatment with the chloroform extract of G. delavayi flower. Although the activities of BACE2 and cathepsin D were not changed, the expression of Aβ degrading enzyme NEP increased remarkably. Our experiments have clearly showed that the chloroform extract of G. delavayi flower inhibits the generation of β-amyloid by specifically inhibiting β-secretase and increases the expression of NEP which fastens the degradation of Aβ, exhibiting the effect of decreasing Aβ accumulation in APP/PS1 CHO cells. These results suggest that the active components from the chloroform extract of G. delavayi flower have a further prospect to be developed as potential anti-Aβ drug.

In wastewater treatment, biological nitrogen removal is an important topic, and the optimal condition for it is a mesophilic environment. This study developed a thermophilic microbial fuel cells (thermo-MFCs) equipped with a hydrophobic membrane electrode to remove and recover ammonia and water from leachate. The results were compared with those of the mesophilic MFCs (meso-MFCs) and they show that the current and power densities for meso-MFCs are higher. The ammonia removal efficiencies of thermo-MFCs are 83% (closed circuit) and 60% (open circuit), higher than those of closed- and open-circuit meso-MFCs (48 and 38%, respectively). Water vapor, the main recovery water flux for the thermo-MFCs, provided 36.5 L m− 2 d− 1 using the closed-circuit mode without applied energy. Moreover, thermo-MFCs and meso-MFCs can be restored within 24 h even under inhibition by using 7200 mg L− 1 ammonia. The proposed process presents an economic and ecofriendly method to not only recover water and ammonia from leachate but also alleviate ammonia inhibition.

The nanosilver-based antibacterial composite film used as food packaging has a potential hazard of silver leakage into the human body. In this study, hyperbranched polyamide-amine (HPAMAM) was used as a template, reducing agent, and stabilizer to synthesize Ag nanoparticles (Ag NPs) in situ, and then HPAMAM anchored Ag NPs onto oxidized cellulose to construct a regenerated cellulose film with a low silver leakage for antibacterial food packaging. Alkali hydroxide/urea solution was used to dissolve cotton fibers, and the hydroxyl groups at C-2 and C-3 of the glucose residues were oxidized to two aldehyde groups by NaIO

The cytochrome P450 enzymes (P450s or CYPs) are heme-containing enzymes which catalyze a wide range of oxidation reactions in nature. In our previous study, a rare multifunctional P450 AstB was found, which can dually oxidize two methyl groups (C-19 and C-21) of preasperterpenoid A to asperterpenoid A with 3-carboxyl and 11-hydroxymethyl groups. However, the oxidation order of C-19 and C-21 catalyzed by AstB is unclear. In order to reveal this oxidation order, probable pathways catalyzed by AstB were proposed, and the oxidation order of C-19 and C-21 was obtained by quantum chemistry calculations. The potential intermediates (three new asperterpenoids D–F, 1–3) were obtained through the chemical investigation on the extract of the transformant strain and chemical conversions, which were used as the standards to detect their existences in the extract of the transformant strain with HPLC-MS. Combined with the quantum chemistry calculation and the HPLC-MS analysis, the catalyzed order of AstB in asperterpenoid A biosynthesis was revealed. Furthermore, the mPTPB inhibition of obtained asperterpenoids was evaluated, and the results showed that 3-carboxyl and the oxidation station of C-21 would be the key factors for mPTPB inhibition of asperterpenoids.

Despite marked improvements in supportive care, the mortality rate of acute respiratory distress syndrome due to the excessive inflammatory response caused by direct or indirect lung injury induced by viral or bacterial infection is still high. In this study, we explored the anti‐inflammatory effect of FJU‐C28, a new 2‐pyridone‐based synthetic compound, on lipopolysaccharide (LPS)‐induced inflammation in vitro and in vivo models. FJU‐C28 suppressed the LPS‐induced mRNA and protein expression of iNOS, COX2 and proinflammatory cytokines. The cytokine protein array results showed that LPS stimulation enhanced the secretion of IL‐10, IL‐6, GCSF, Eotaxin, TNFα, IL‐17, IL‐1β, Leptin, sTNF RII, and RANTES. Conversely, the LPS‐induced secretion of RANTES, TIMP1, IL‐6, and IL‐10 was dramatically suppressed by FJU‐C28. FJU‐C28 suppressed the LPS‐induced expression of RANTES, but its parental compound FJU‐C4 was unable to diminish RANTES in cell culture media or cell lysates. FJU‐C28 blocked the secretion of IL‐6 and RANTES in LPS‐activated macrophages by regulating the activation of JNK, p38 mitogen‐activated protein kinase (MAPK) and nuclear factor‐κB (NF‐κB). FJU‐C28 prevented the LPS‐induced decreases in lung function including vital capacity (VC), lung compliance (C chord), forced expiratory volume at 100 ms (FEV100), and forced vital capacity (FVC) in mice with LPS‐induced systemic inflammatory responses. FJU‐C28 also reduced neutrophil infiltration in the interstitium, lung damage and circulating levels of IL‐6 and RANTES in mice with systemic inflammation. In conclusion, these findings suggest that FJU‐C28 possesses anti‐inflammatory activities to prevent endotoxin‐induced lung function decrease and lung damages by down‐regulating proinflammatory cytokines including IL‐6 and RANTES via suppressing the JNK, p38 MAPK and NF‐κB signaling pathways., Acute exposure to lipopolysaccharide (LPS) can activate nuclear factor‐κB (NF‐κB), p38 mitogen‐activated protein kinase (MAPK), and JNK signaling pathways to induce the expression of proinflammatory cytokines such as IL‐6 and CCL5. The LPS‐induced IL‐6 can be secreted to the extracellular environment and then bind to membrane‐bound IL‐6R to induce IL‐6/signal transducer and activator of transcription 3 (STAT3) signaling to sustain the production of IL‐6 potentially modulating the severity of the host inflammatory response. LPS/TLR4‐induced production of IL‐6 is suppressed by FJU‐C28 through inhibiting the activation of NF‐κB, p38 MAPK and JNK signal pathways; and the activation of IL‐6/STAT3 signaling also is inhibited via reducing the levels of STAT3 protein.

Rhizopus oryzae is a fungus used to ferment tempeh in Indonesia and is generally recognized as safe (GRAS) for human consumption by the USA FDA. We previously assessed the effect of a tempeh extract on cortisol levels in zebrafish but did not include behavioral studies. Here, we measured the GABA content in three strains of Rhizopus oryzae, two isolated by us (MHU 001 and MHU 002) and one purchased. We then investigated the effect of tempeh on cortisol and the gut microbiota in a zebrafish experimental model. GABA concentration was the highest in MHU 002 (9.712 ± 0.404 g kg−1) followed by our MHU 001 strain and the purchased one. The fish were divided into one control group fed a normal diet and three experimental groups fed soybean tempeh fermented with one of the three strains of Rhizopus oryzae. After two weeks, individual fish were subjected to unpredicted chronic stress using the novel tank diving test and the tank light–dark test. Next-generation sequencing was used to analyze gut microbial communities and RT-PCR to analyze the expression of BDNF (brain-derived neurotrophic factor) gene and of other genes involved in serotonin signaling/metabolism in gut and brain. Tempeh-fed zebrafish exhibited increased exploratory behavior (less stress) in both tank tests. They also had significantly reduced gut Proteobacteria (include E. coli) (51.90% vs. 84.97%) and significantly increased gut Actinobacteria (include Bifidobacterium spp.) (1.80% vs. 0.79%). The content of Bifidobacteriumadolescentis, a “psychobiotic”, increased ten-fold from 0.04% to 0.45%. Tempeh also increases BDNF levels in zebrafish brain. Rhizopus oryzae MHU 001 greatly improved the anti-stress effect of tempeh and microbiota composition in zebrafish gut.

An innovative immunosuppressant with a minimally invasive delivery system has emerged in the biomedical field. The application of biodegradable and biocompatible polymer forms, such as hydrogels, scaffolds, microspheres, and nanoparticles, in transplant recipients to control the release of immunosuppressants can minimize the risk of developing unfavorable conditions. In this review, we summarized several studies that have used implantable immunosuppressant delivery to release therapeutic agents to prolong allograft survival. We also compared their applications, efficacy, efficiency, and safety/side effects with conventional therapeutic-agent administration. Finally, challenges and the future prospective were discussed. Collectively, this review will help relevant readers understand the different approaches to prevent transplant rejection in a new era of therapeutic agent delivery.

Due to the increasing prevalence of drug-resistant fungi and the limitations of current treatment strategies to fungal infections, exploration and development of new antifungal drugs or substituents are necessary. In the study, a novel antimicrobial peptide, named Sparamosin, was identified in the mud crab Scylla paramamosain, which contains a signal peptide of 22 amino acids and a mature peptide of 54 amino acids. The antimicrobial activity of its synthetic mature peptide and two truncated peptides (Sparamosin1–25 and Sparamosin26–54) were determined. The results showed that Sparamosin26–54 had the strongest activity against a variety of Gram-negative bacteria, Gram-positive bacteria and fungi, in particular had rapid fungicidal kinetics (killed 99% Cryptococcus neoformans within 10 min) and had potent anti-biofilm activity against C. neoformans, but had no cytotoxic effect on mammalian cells. The RNA-seq results showed that after Sparamosin26–54 treatment, the expression of genes involved in cell wall component biosynthesis, cell wall integrity signaling pathway, anti-oxidative stress, apoptosis and DNA repair were significantly up-regulated, indicating that Sparamosin26–54 might disrupt the cell wall of C. neoformans, causing oxidative stress, DNA damage and cell apoptosis. The underlying mechanism was further confirmed. Sparamosin26–54 could bind to several phospholipids in the cell membrane and effectively killed C. neoformans through disrupting the integrity of the cell wall and cell membrane observed by electron microscope and staining assay. In addition, it was found that the accumulation of reactive oxygen species (ROS) increased, the mitochondrial membrane potential (MMP) was disrupted, and DNA fragmentation was induced after Sparamosin26–54 treatment, which are all hallmarks of apoptosis. Taken together, Sparamosin26–54 has a good application prospect as an effective antimicrobial agent, especially for C. neoformans infections.

C34H56O6⋅0.25(C4H8O2), orthorhombic, P212121 (no. 19), a = 8.17152(14) Å, b = 17.6728(3) Å, c = 23.1916(5) Å, V = 3349.18(11) Å3, Z = 4, R gt(F) = 0.0416, wR ref (F 2) = 0.1143, T = 293 K.

C24H21F6NO3, monoclinic, P21/c (no. 14), a = 16.6493(9) Å, b = 15.3005(8) Å, c = 8.8554(5) Å, β = 99.746(6)°, V = 2223.3(2) Å3, Z = 4, R gt (F) = 0.0444, wR ref (F 2) = 0.1094, T = 100 K.

Fluorescein isothiocyanate-dextrans (FDs) of different molecular weights were infused into corn, waxy rice, tapioca, and potato starches under atmospheric and high hydrostatic pressures (HHP). FD4, FD10, FD20, and FD40 (Mw 4000, 10,000, 20,000, and 40,000, respectively) were used as infusion materials. Confocal laser scanning microscopy confirmed that all FDs except FD40 infused into corn, waxy rice, and tapioca starches. However, no FDs infused into potato starch. Corn starch had the highest amounts of infused FDs. As molar mass increased, the amount of infused FD decreased in all starches. The infused amounts of FDs in corn starch were similar at 200–300 MPa and atmospheric pressure. Infusion of FDs at 400 MPa was reduced due to partial gelatinization. These results confirm that infusion efficiency is inversely proportional to the molecular weight of the infused material and large materials (Mw > 40,000) cannot be infused into starch granules under atmospheric pressure or HHP. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10068-021-00972-2.

Aberrant activation of the Ras–ERK signaling pathway drives many important cancer phenotypes, and several inhibitors targeting such pathways are under investigation and/or approved by the FDA as single- or multi-agent therapy for patients with melanoma and non–small-cell lung cancer (NSCLC). Here, we show that betulinic acid (BA), a natural pentacyclic triterpenoid, inhibits cell proliferation, and induces apoptosis and protective autophagy in NSCLC cells. Thus, the cancer cell killing activity of BA is enhanced by autophagy inhibition. Mitogen-activated protein kinases, and especially ERK that facilitates cancer cell survival, are also activated by BA treatment. As such, in the presence of ERK inhibitors (ERKi), lung cancer cells are much more sensitive to BA. However, the dual treatment of BA and ERKi results in increased protective autophagy and AKT phosphorylation. Accordingly, inhibition of AKT has a highly synergistic anticancer effect with co-treatment of BA and ERKi. Notably, autophagy inhibition by hydroxychloroquine (HCQ) increases the response of lung cancer cells to BA in combination with ERKi. In vivo, the three-drug combination (BA, ERKi, and HCQ), resulted in superior therapeutic efficacy than single or dual treatments in the xenograft mouse model. Thus, our study provides a combined therapy strategy that is a highly effective treatment for patients with NSCLC.

C 20 H 14 F 6 O 2 ${\text{C}}_{20}{\text{H}}_{14}{\text{F}}_{6}{\text{O}}_{2}$ , monoclinic, P21/c (no. 14), a = 14.791(2) Å, b = 8.5303(9) Å, c = 15.531(3) Å, β = 115.474(19)°, V = 1769.1(5) Å3, Z = 4, R g t ${R}_{gt}$ (F) = 0.0574, w R ref $w\,{R}_{\text{ref}}$ (F 2) = 0.1451, T = 100 K. CCDC no.: 2016723

C 19 H 14 F 4 O 2 ${\text{C}}_{19}{\text{H}}_{14}{\text{F}}_{4}{\text{O}}_{2}$ , triclinic, P 1 ‾ $P‾{1}$ (no. 2), a = 8.1539(7) Å, b = 8.8584(6) Å, c = 11.8025(9) Å, α = 73.186(7)°, β = 76.184(7)°, γ = 69.512(7)°, V = 755.39(11) Å3, Z = 2, R g t ${R}_{gt}$ (F) = 0.0436, w R ref $w{R}_{\text{ref}}$ (F 2) = 0.0965, T = 100 K.

C32H52O5, monoclinic, P21 (no. 4), a = 11.816(2) Å, b = 7.4064(15) Å, c = 17.101(3) Å, β = 97.01(3)°, V = 1485.5(5) Å3, Z = 2, R gt(F) = 0.0543, wR ref(F 2) = 0.1501, T = 293(2) K.

C39H54O5, monoclinic, P21 (no. 4), a = 6.98138(17) Å, b = 37.9050(6) Å, c = 7.28644(16) Å, β = 117.789(3)°, V = 1705.82(8) Å3, Z = 2, R gt (F) = 0.0326, wR ref(F 2) = 0.0872, T = 293(2) K.

C31H48O5, monoclinic, P21 (no. 4), a = 11.0421(3) Å, b = 6.49710(16) Å, c = 20.4687(4) Å, β = 97.922(2)°, V = 1454.45(6) Å3, Z = 2, R gt(F) = 0.0382, wR ref(F 2) = 0.1024, T = 293(2) K.

The rapid industrialization and economic development in the Pearl River Delta (PRD) region of southern China have led to a substantial increase in anthropogenic emissions and hence frequent haze pollution over the past two decades. In early January 2017, a severe regional haze pollution episode was captured in the PRD region, with a peak PM2.5 concentration of around 400μgm-3, the highest value ever reported at this site. During the haze episode, elevated concentrations of oxygenated volatile organic compounds (OVOCs, 33±16 ppbv) and organic matter (41±15μg m-3) were observed, indicating the enhanced roles of secondary organic aerosols (SOAs) in the formation of haze pollution. Water-soluble organic carbon (WSOC, 12.8±5.5μg C m-3) dominated the organic aerosols, with a WSOC/OC ratio of 0.63±0.12 and high correlation (R=0.85) with estimated secondary organic carbon (SOC), suggesting the predominance of a secondary origin of the measured organic aerosols during the haze episode. Four carboxylic acids (oxalic, acetic, formic, and pyruvic acids) were characterized in the aerosols (1.30±0.38μgm-3) and accounted for 3.6±1.2% of WSOC in carbon mass, with oxalic acid as the most abundant species. The simultaneous measurements of volatile organic compounds (VOCs), OVOCs, and organic acids in aerosols at this site provided an opportunity to investigate the relationship between the precursors and the products, as well as the potential formation pathways. Water-soluble aldehydes and ketones, predominantly produced via the oxidation of anthropogenic VOCs (mainly propane, toluene, n-butane, and m, p-xylene), were the main contributors of the organic acids. The formation of OVOCs is largely attributed to gas-phase photochemical oxidation, whereas the WSOC and dicarboxylic acids were produced from both photochemistry and nocturnal heterogeneous reactions. These findings provided further insights into the oxidation and evolution of organic compounds during the haze pollution episode.

Background: The focus of this study was the selection of a single chain variable fragment antibody (scFv) against subtilisin BRC, a fibrinolytic enzyme using phage display, and to characterize the interaction between the antibody and subtilisin BRC. Methods: The subtilisin BRC-specific phage clones were selected using Griffin.1 scFv phage library and sequenced. The gene of subtilisin BRC-specific scFv (scFv-BRC) from selected phage clone was expressed in E. coli and scFv-BRC was characterized. Molecular modeling of the three-dimensional (3D) structures of scFv-BRC was performed using MODELLER 9.19 modeling software and assessed by PROCHEK. Molecular docking of subtilisin BRC with scFv-BRC was carried out using PATCHDOCK. Results: The size of scFv-BRC gene is 635bp and it consists of 54bp of heavy chain region (VH), 336bp of light chain region (VL), 45bp of a linker. scFv-BRC was actively expressed by E. coli expression vector pET28a-scFv in E. coli BL21 (DE3), and the amount of expressed scFv-BRC was about 50 mg/L. Its molecular weight is ~26kDa. The CDR domain of scFv-BRC consists of 6 amino acids in CDR L1, 3 amino acids in CDR L2 and 9 amino acids in CDR L3. Docking results of subtilisin BRC and scFv-BRC showed global energy of - 56.29 kJ/mol. Furthermore, the results showed that amino acid residues in subtilisin BRC for binding with scFv-BRC are Tyr6, Ser182, Ser204, and Gln206. Conclusion: scFv against subtilisin BRC selected using phage display showed relatively strong binding energy with subtilisin BRC. The amino acid residues in subtilisin BRC for binding with scFv-BRC are not relevant to that in subtilisin BRC for binding with its substrates. These results suggested that scFv-BRC can be used as a ligand for detection and affinity purification of subtilisin BRC.

An enantioselective sulfenylation/semipinacol rearrangement of 1,1-disubstituted and trisubstituted allylic alcohols was accomplished with a chiral Lewis base and a chiral Brønsted acid as cocatalysts, generating various β-arylthio ketones bearing an all-carbon quaternary center in moderate to excellent yields and excellent enantioselectivities. These chiral arylthio ketone products are common intermediates with many applications, for example, in the design of new chiral catalysts/ligands and the total synthesis of natural products. Computational studies (DFT calculations) were carried out to explain the enantioselectivity and the role of the chiral Brønsted acid. Additionally, the synthetic utility of this method was exemplified by an enantioselective total synthesis of (-)-herbertene and a one-pot synthesis of a chiral sulfoxide and sulfone.

In recent years, many efforts have been devoted to boost molecular oxygen activation in semiconductor. This is because the reactive oxygen species (ROS) induced by molecular oxygen activation have been confirmed to play a great role in environmental remediation. Herein, we proposed a self-assembled plasmonic p-n heterojunction of WO3/Ag@Ag2O with enhanced molecular oxygen activation ability under visible and near-infrared (NIR) light irradiation. The prepared p-n heterojunction is favorable for the migration and separation of photo-generated hot charge carriers, which can promote the transformation of molecular oxygen to ROS with enhanced photocatalytic performance for norfloxacin (NOR) decomposition. The trapping experiments and Electron spin response (ESR) spectra demonstrate that both superoxide ( O2−) and singlet oxygen (1O2) are the main functional ROS for NOR degradation. The yield amount of O2− in the prepared hybrid catalyst is higher than that of pristine catalyst from nitrotetrazolium blue chloride (NBT) degradation. The sustainable generation of 1O2 is mainly ascribed to the charge transfer and energy transfer. Fluorescence spectra method is employed to confirm the generation of hydrogen peroxide (H2O2). The intermediates of NOR degradation are identified by LC/MS, and the possible degradation pathway is proposed in detail. A reasonable charge transfer pathway for the ultra-high hot charge carrier separation is studied. In addition, the as-prepared hybrid composite shows excellent photocatalytic performance for the degradation of rhodamine B (RhB) and ciprofloxacin (CIP). This study provides a promising avenue for fabrication of semiconductor with boosting molecular oxygen activation.

Benzo[a]pyrene (BaP), a common environmental pollutant, can modulate the immune-associated signal pathway NF-κB, which is one of the critical signal pathways involved in various immune responses. BaP exposure usually generates reactive oxygen species (ROS), but whether ROS are predominantly involved in the modulation mechanism of the NF-κB pathway has not been clearly understood. In this study, an in vivo examination of Oryzias melastigma demonstrated that BaP exposure led to a down-regulation of the NF-κB pathway and increased levels of ROS. Conversely, in vitro results using the medaka liver cell line DIT-29 and a widely applied H2O2 method showed the opposite: up-regulation of the NF-κB pathway. However, the down-regulation of NF-κB upon BaP exposure in vitro was inhibited by the addition of a ROS inhibitor, indicating ROS are involved in the modulation of NF-κB. The discrepancy between in vivo and in vitro results of ROS impacts on NF-κB activation might be related to the concentration and persistence of ROS. Using a modified luminol detection system, BaP was found to generate sustained physiological concentrations of ROS for 24 h, while an H2O2 bolus generated ROS for less than 30 min. Furthermore, a steady-state sub-micromolar H2O2 system (H2O2ss) was developed in parallel as a positive control of ROS, by which H2O2 could be maintained for 24 h. Comparative evaluation using H2O2, H2O2ss and BaP exposures on the medaka cell line with pGL4.32 demonstrated that the persistent physiological concentrations of ROS generated upon BaP exposure or treatment with H2O2ss inhibited the NF-κB pathway, but direct H2O2 exposure had the opposite effect. Moreover, a western-blot assay and EMSA detection further confirmed the modulation of the NF-κB pathway in DIT-29. Taken together, this study shows that BaP exposure inhibits the NF-κB pathway by generating sustained physiological concentrations of ROS.

The nature of muscle-bone crosstalk has been historically considered to be only mechanical, where the muscle is the load applier while bone provides the attachment sites. However, this dogma has been challenged with the emerging notion that bone and muscle act as secretory endocrine organs affect the function of each other. Biochemical crosstalk occurs through myokines such as myostatin, irisin, interleukin (IL)-6, IL-7, IL-15, insulin-like growth factor-1, fibroblast growth factor (FGF)-2, and β-aminoisobutyric acid and through bone-derived factors including FGF23, prostaglandin E(2), transforming growth factor β, osteocalcin, and sclerostin. Aside from the biochemical and mechanical interaction, additional factors including aging, circadian rhythm, nervous system network, nutrition intake, and exosomes also have effects on bone-muscle crosstalk. Here, we summarize the current research progress in the area, which may be conductive to identify potential novel therapies for the osteoporosis and sarcopenia, especially when they develop in parallel.

Physicochemical properties of acetylated (AC), cross-linked (CL), and hydroxypropylated (HP) chestnut starches were investigated. Modified chestnut starch showed low RS and amylose contents. AC revealed the highest solubility and HP showed the highest swelling power at 60 °C. CL showed the lowest solubility and swelling power at both 60 and 90 °C. AC and HP showed a lower pasting temperature and higher peak viscosity than native chestnut starch (NC). Modified chestnut starch formed gels at higher solid content than NC. CL had the lowest freeze-thaw stability, and AC and HP showed the strongest tolerance to freeze-thaw cycles. Amylopectin melting enthalpy of NC dramatically increased over the first 2 days and continued increasing gradually until day 24. On the other hand, all the modified chestnut starches showed a slight increase in amylopectin melting enthalpy, indicating retarded retrogradation. CL showed the lowest degree of retrogradation, followed by HP, AC, and NC.

In this study, ternary catalyst g-C3N4/Ag2CO3/graphene oxide was synthesized through a simple chemical precipitation method at room temperature. The CN/AC/GO composite was employed to degrade antibiotics under visible light irradiation. And the results indicated that the composite possessed excellent photocatalytic performance, which could remove 81.6% tetracycline (TC) after 60 min of irradiation. The PL, EIS, PC and UV–vis DRS tests demonstrated that enhanced photocatalytic efficiency could be attributed to rapid charge transfer, low recombination rate of photo-induced electron-hole pairs, as well as superior light absorption capability. Moreover, three-dimensional excitation-emission matrix fluorescence spectra (3D EEMs) were employed to further grasp the behaviors of TC molecules in the process of degradation reaction. In addition, the liquid chromatography-mass spectrometry (LC-MS) was carried out to explore the intermediates during the photocatalytic reaction. Meanwhile, the influences of initial TC concentration, light source, supporting electrolytes and water sources were explored from the perspective of practical application. Furthermore, the appearance of a small amount of Ag nanoparticles (NPs) not only accelerated the charge transfer, but also improved the stability of catalyst. The composite also possessed high stability and reusability, which were essential in practical application.