[WANG Haidong's experience in treatment of wrist rheumatoid arthritis with acupotomy mobilization at the muscle regions of three yang meridians of hand].

The paper introduces professor WANG Haidong's clinical experience in treatment of wrist rheumatoid arthritis with acupotomy mobilization at the muscle regions (sinews/fascia) of three yang meridians of hand. Professor WANG Haidong believes that wrist rheumatoid arthritis belongs to the disorder of meridian muscle regions and is especially associated with the damage of the muscle regions of three yang meridians of hand running through the wrist. Under the guidance of meridian muscle region theory, on the basis of modern anatomy, and the treatment principle, "needling the affected areas may treat disorders of sinews/fascia and dysfunction of meridians simultaneously", acupotomy mobilization is adopted to balance sinews/fascia and bones, operated directly at the involved meridian muscle regions. Besides the foci (palpable knotted sites) on the distribution of muscle regions, acupoints along the affected meridians are stimulated in combination. With this therapy, after determining the location of illness, both the disorder of sinews/fascia and that of meridians can be treated.

Allelopathic effects of phenolic acid extracts on Morchella mushrooms, pathogenic fungus, and soil-dominant fungus uncover the mechanism of morel continuous cropping obstacle.

The prominent problem of continuous cropping obstacle has been frustrating the morel farming. To deepen the understanding on morel continuous cropping obstacle, the allelopathic effects of phenolic acid extracts from morel continuous cropping soils on growth and development of Morchella sextelata, M. eximia, M. importuna, pathogenic fungus Fusarium sp. and soil-dominant fungus Chaetomium sp. were investigated. These effects were expressed as response index (RI). Under actual content of phenolic acids (6.150 µg/g fresh mixed continuous cropping soil), the mycelial growth of all tested morel strains was inhibited (RI < 0), while the allelopathic effect of control phenolic acids (4.252 µg/g fresh mixed control soil) was between promotion and inhibition, which suggested that the phenolic acid extracts from morel continuous cropping soils may exhibit certain extent of autotoxicity for the existence of morel-specific allelochemicals. In addition, the aggravated pigmentation and reduced occurrence of sclerotium in three Morchella fungi at growth inhibitory concentrations of phenolic acids indicated the induction of morel strain aging. Meanwhile, most concentrations of phenolic acids showed stimulatory effects on sporulation of Fusarium sp. and Chaetomium sp. (RI > 0), manifesting the enrichment of soil-borne pathogenic fungi and dominance of certain fungal population in soil ecosystem. Collectively, the allelopathic effects of phenolic acid extracts play an instrumental role in morel continuous cropping obstacle. The study will be beneficial for healthy development of morel artificial cultivation.

Structure of the Mating-Type Genes and Mating Systems of Verpa bohemica and Verpa conica (Ascomycota, Pezizomycotina).

Verpa spp. are potentially important economic fungi within Morchellaceae. However, fundamental research on their mating systems, the key aspects of their life cycle, remains scarce. Fungal sexual reproduction is chiefly governed by mating-type genes, where the configuration of these genes plays a pivotal role in facilitating the reproductive process. For this study, de novo assembly methodologies based on genomic data from Verpa spp. were employed to extract precise information on the mating-type genes, which were then precisely identified in silico and by amplifying their single-ascospore populations using MAT-specific primers. The results suggest that the MAT loci of the three tested strains of V. bohemica encompassed both the MAT1-1-1 and MAT1-2-1 genes, implying homothallism. On the other hand, amongst the three V. conica isolates, only the MAT1-1-1 or MAT1-2-1 genes were present in their MAT loci, suggesting that V. conica is heterothallic. Moreover, bioinformatic analysis reveals that the three tested V. bohemica strains and one V. conica No. 21110 strain include a MAT1-1-10 gene in their MAT loci, while the other two V. conica strains contained MAT1-1-11, exhibiting high amino acid identities with those from corresponding Morchella species. In addition, MEME analysis shows that a total of 17 conserved protein motifs are present among the MAT1-1-10 encoded protein, while the MAT1-1-11 protein contained 10. Finally, the mating type genes were successfully amplified in corresponding single-ascospore populations of V. bohemica and V. conica, further confirming their life-cycle type. This is the first report on the mating-type genes and mating systems of Verpa spp., and the presented results are expected to benefit further exploitation of these potentially important economic fungi.

Large-Scale Field Cultivation of Morchella and Relevance of Basic Knowledge for Its Steady Production.

Morels are one of the most highly prized edible and medicinal mushrooms worldwide. Therefore, historically, there has been a large international interest in their cultivation. Numerous ecological, physiological, genetic, taxonomic, and mycochemical studies have been previously developed. At the beginning of this century, China finally achieved artificial cultivation and started a high-scale commercial development in 2012. Due to its international interest, its cultivation scale and area expanded rapidly in this country. However, along with the massive industrial scale, a number of challenges, including the maintenance of steady economic profits, arise. In order to contribute to the solution of these challenges, formal research studying selection, species recognition, strain aging, mating type structure, life cycle, nutrient metabolism, growth and development, and multi-omics has recently been boosted. This paper focuses on discussing current morel cultivation technologies, the industrial status of cultivation in China, and the relevance of basic biological research, including, e.g., the study of strain characteristics, species breeding, mating type structure, and microbial interactions. The main challenges related to the morel cultivation industry on a large scale are also analyzed. It is expected that this review will promote a steady global development of the morel industry based on permanent and robust basic scientific knowledge.

Ultrastructure and Physiological Characterization of Morchella Mitospores and Their Relevance in the Understanding of the Morel Life Cycle.

Morels, which belong to the Ascomycete genus Morchella, are highly valued edible fungi treasured by gourmet chefs worldwide. Some species are saprotrophic and others are able to form facultative mycorrhizal-like associations with plant roots without establishing true ectomycorrhizal symbioses. In general, it is considered that the formation of asexual spores, or mitospores, is an important step in the life cycle of morels. However, ultrastructure characterization and physiological attributes of morel mitospores have received little attention. In this contribution, the mitospores of M. sextelata were successfully induced under laboratory conditions and their ultrastructure, occurrence, germination, physiological characteristics and mating type gene structure were studied. Mitospore production was closely related to aeration, nutrition and humidity conditions. The average germination rate of mitospores on different media and under various induction stimuli was very low, with an average of 1/100,000. Based on the ultrastructure characterization, low germination rate, growth rate decline, rapid aging and mating genotyping, it was concluded that the mitospores of M. sextelata had lost their conventional function as conidia and might act more as mate sperm-like (gamete) structures. Thus, this study contributed to a deeper understanding of the life cycle of the economically and ecologically important morel fungal group.

Activity Assay of Amylase and Xylanase Is Available for Quantitative Assessment of Strain Aging in Cultivated Culinary-Medicinal Morchella Mushrooms (Ascomycotina).

Strain aging has been mainly contributing to the "uncertainty" of Morchella farming. The situation calls for urgent quantitative assessment of strain aging in cultivated Morchella mushrooms. In this paper, systemic senescence of the productive strains of M. eximia, M. importuna, and M. sextelata was achieved through successive subculturing to provide subcultures with different degree of aging for further studies. Then the quantitative assessment of morel strain aging was conducted by activity assay of amylase and xylanase using dinitrosalicylic acid (DNS) method. The results suggested that both activity of amylase and xylanase decreased along with the rise of subculture times. Meanwhile, the correlation between xylanase activity and time of subculturing in the tested morel strains was higher than that of amylase assay. Consequently, assay of amylase and xylanase activity by DNS method can be used in the quantitative assessment of morel strain aging, and assay of xylanase activity is the better alternative. The work will improve the settlement of "uncertainty" in the morel industry and thus be beneficial for stable development of morel farming.

The prokaryotic community, physicochemical properties and flavors dynamics and their correlations in fermented grains for Chinese strong-flavor Baijiu production.

Fermented grain (FG), a complex and unique ecosystem, is the main microbial habitats, biochemical reaction system and direct source of flavor compounds for the Chinese strong-flavor Baijiu (CSFB) production. However, the dynamics of physicochemical properties, prokaryotic community and flavor compounds of FGs during the long-term fermentation process are still not completely clear. Here, the above topics on FGs in the actual production process were comprehensively studied by using a combination of physicochemical analysis, GC-MS detection and Illumina HiSeq sequencing methods. The whole fermentation process could be divided into two stages including early (0-25d) and the later stage (25-60d) based on the dynamics of FG physicochemical properties and the changes of prokaryotic community diversity. A total of 41phyla and 364 genera were detected, and 9 of them were dominant genera in FG complex ecosystem, including Lactobacillus, Pediococcus, Ochrobactrum, Bacillus etc. Among them, the dynamics of 29 top10 genera in FGs were mainly influenced by the starch and total acid, followed by NH4+ and ethanol, and 7 genera (hubs, e.g., Clostridium, Methanosaeta, Bacillus, etc.) of them may play important roles in FG ecosystem stability. A total of 71 volatiles including 33 esters, 14 alcohols, 9 fatty acids, 5 phenols, and 10 other compounds were detected in the FGs, and most of them formed in the early stage. Some important flavor substances (e.g., ethyl octanoate, 3-methylbutanol, hexanoate, etc.) increased in the later stage. Moreover, the formation of some flavor compound might require multiple microbes involved. For instance, ten of the top10 genera, including Lactobacillus, Clostridium, Methanosarcina, Sedimentibacter, Bacillus, etc., were significantly and positively correlated with four important esters. This study may help to clarify the complex correlations among prokaryotic community, physicochemical properties and flavors, allow the improvement of CSFB quality by using bioaugmentation and/or controlling environmental factors, and shed more light on the ecological rules guiding community assembly in FGs.

The thermal/pH-sensitive drug delivery system encapsulated by PAA based on hollow hybrid nanospheres with two silicon source.

The synthesis of drug delivery systems based on hollow mesoporous silica nanoparticles (MSNs) is still a major challenge. In this work, the hollow hybrid MSNs were successfully prepared by cetyltrimethylammonium bromide-directed sol-gel process and one-step hydrothermal treatment process. The hollow hybrid MSNs had hybrid ethane-bridged frameworks with the uniform particle size (250 nm) and mesoporous pore diameter (3.7 nm). The polyacrylic acid (PAA) encapsulated drug delivery system based on hollow hybrid MSNs was prepared by using silanization, surface modification, doxorubicin hydrochloride (DOX) loading, and PAA coating. Drug encapsulation and release behavior at different temperatures and pH were studied by using DOX as a model guest molecule. The results displayed that the modified hollow ethane-bridged MSNs possessed good biocompatibility and excellent thermal/pH-dual-sensitive drug release property. This novel thermal/pH-sensitive drug delivery system based on hollow ethane-bridged MSNs has the advantages of feasible synthesis, no cytotoxicity, and good drug loading capacity, which may have potential applications in the anticancer therapy.

Discovery and identification of medium-chain fatty acid responsive promoters in Saccharomyces cerevisiae.

Medium-chain fatty acids (MCFAs) and their derivatives are important chemicals that can be used in lubricants, detergents, and cosmetics. MCFAs can be produced in several microbes, although production is not high. Dynamic regulation by synthetic biology is a good method of improving production of chemicals that avoids toxic intermediates, but chemical-responsive promoters are required. Several MCFA sensors or promoters have been reported in Saccharomyces cerevisiae. In this study, by using transcriptomic analysis of S. cerevisiae exposed to fatty acids with 6-, 12-, and 16-carbon chains, we identified 58 candidate genes that may be responsive to MCFAs. Using a fluorescence-based screening method, we identified MCFA-responsive promoters, four that upregulated gene expression, and three that downregulated gene expression. Dose-response analysis revealed that some of the promoters were sensitive to fatty acid concentrations as low as 0.02-0.06 mM. The MCFA-responsive promoters reported in this study could be used in dynamic regulation of fatty acids and fatty acid-derived products in S. cerevisiae.

Gating Properties of Mutant Sodium Channels and Responses to Sodium Current Inhibitors Predict Mexiletine-Sensitive Mutations of Long QT Syndrome 3.

BACKGROUND: Long QT syndrome 3 (LQT3) is caused by SCN5A mutations. Late sodium current (late I Na) inhibitors are current-specific to treat patients with LQT3, but the mechanisms underlying mexiletine (MEX) -sensitive (N1325S and R1623Q) and -insensitive (M1652R) mutations remains to be elucidated. METHODS: LQT3 patients with causative mutations were treated with oral MEX following i.v. lidocaine. Whole-cell patch-clamp techniques and molecular remodeling were used to determine the mechanisms underlying the sensitivity to MEX. RESULTS: Intravenous administration of lidocaine followed by MEX orally in LQT patients with N1325S and R1623Q sodium channel mutation shortened QTc interval, abolished arrhythmias, and completely normalized the ECG. In HEK293 cells, the steady-state inactivation curves of the M1652R channels were rightward shifted by 5.6 mV relative to the WT channel. In contrast, the R1623Q mutation caused a leftward shift of the steady-state inactivation curve by 15.2 mV compared with WT channel, and N1325S mutation did not affect steady-state inactivation (n = 5-13, P < 0.05). The extent of the window current was expanded in all three mutant channels compared with WT. All three mutations increased late I Na with the greatest amplitude in the M1652R channel (n = 9-15, P < 0.05). MEX caused a hyperpolarizing shift of the steady-state inactivation and delayed the recovery of all three mutant channels. Furthermore, it suppressed late I Na in N1325S and R1623Q to a greater extent compared to that of M1652R mutant channel. Mutations altered the sensitivity of Nav1.5 to MEX through allosteric mechanisms by changing the conformation of Nav1.5 to become more or less favorable for MEX binding. Late I Na inhibitors suppressed late I Na in N1325S and R1623Q to a greater extent than that in the M1652R mutation (n = 4-7, P < 0.05). CONCLUSION: The N1325S, R1623Q, and M1652R mutations are associated with a variable augmentation of late I Na, which was reversed by MEX. M1652R mutation changes the conformation of Nav1.5 that disrupt the inactivation of channel affecting MEX binding, corresponding to the poor response to MEX. The lidocaine test, molecular modeling, and drugs screening in cells expressing mutant channels are useful for predicting the effectiveness of late I Na inhibitors.

Tumor-mediated shape-transformable nanogels with pH/redox/enzymatic-sensitivity for anticancer therapy.

Lack of sufficient tumor penetration of the current nanomedicines is a major reason limiting their clinical success in cancer therapy. In this work, we aimed at the development of a novel biodegradable nanoplatform for the selective and controlled delivery of anticancer agents, with improved tumor permeability and the ability to release ultrasmall nanovesicles in the tumor microenvironment. To this end, positively charged nanogels were obtained through the double-crosslinking of chitosan with an ionic physical gelator and a disulfide-containing chemical crosslinker. After conjugation to an anionic oligomer, the cationic nanogels were transformed into negatively charged nanocarriers (CTCP), enabling effective encapsulation of the cationic anticancer agent doxorubicin (DOX) to generate a biodegradable nanomedicine (DOX@CTCP). DOX@CTCP could maintain sustained DOX release and decreased DOX toxicity. Upon arrival at the tumor tissue, the reductive and lysozyme-high microenvironment drives the cleavage of the nanomedicine to release DOX-carrying nanoblocks of smaller size, which together with their acidic-protonable feature achieves an effective therapeutic delivery into cancer cells. The nanomedicine described here showed excellent biocompatibility/biosafety and enhanced in vivo antitumor efficacy.

Co-occurrence patterns among prokaryotes across an age gradient in pit mud of Chinese strong-flavor liquor.

It is widely believed that the quality and characteristics of Chinese strong-flavor liquor (CSFL) are closely related to the age of the pit mud; CSFL produced from older pit mud tastes better. This study aimed to investigate the alteration and interaction of prokaryotic communities across an age gradient in pit mud. Prokaryotic microbes in different-aged pit mud (1, 6, and 10 years old) were analyzed by Illumina MiSeq sequencing of the 16S rRNA gene. Analysis of the 16S rRNA gene indicated that the prokaryotic community was significantly altered with pit mud age. There was a significant increase in the genera Methanosarcina, Methanobacterium, and Aminobacterium with increased age of pit mud, while the genus Lactobacillus showed a significant decreasing trend. Network analysis demonstrated that both synergetic co-occurrence and niche competition were dominated by 68 prokaryotic genera. These genera formed 10 hubs of co-occurrence patterns, mainly under the phyla Firmicutes, Euryarchaeota, and Bacteroidetes, playing important roles on ecosystem stability of the pit mud. Environmental variables (pH, NH4+, available P, available K, and Ca2+) correlated significantly with prokaryotic community assembly. The interaction of prokaryotic communities in the pit mud ecosystem and the relationship among prokaryotic communities and environmental factors contribute to the higher quality of the pit mud in older fermentation pits.

Interspecific hybridization between cultivated morels Morchella importuna and Morchella sextelata by PEG-induced double inactivated protoplast fusion.

The commercial production of Morchella mushrooms calls for urgent breeding of excellent varieties or strains with appropriate tools, such as protoplast fusion. However, the protoplast fusion in morels has not been studied. In this paper, interspecific hybridization between cultivated morels of M. importuna and M. sextelata by PEG-induced protoplast fusion was conducted. Apart from functional complementation of double inactivated protoplasts, the fusants were characterized by cultural and cultivated characters and molecular markers of random amplified polymorphic DNA (RAPD). The results suggested that the hybrids and their parents showed significant difference in their inoculum recovery time, mycelial growth rate, yield of cultivation and total amino acid content of ascocarps. Moreover, positive barrage reactions were observed between parental strains as well as between each parent and a hybrid line. A dendrogram created on the basis of RAPD fingerprints exhibited three major clusters, in which morel hybrids showed intra-cluster variations, M. sextelata #6 formed an out group, while M. importuna #4 was phylogenetically closer to morel hybrids. All the results demonstrated that real fusants were obtained in our study. Protoplast fusion may provide an ideal alternative for new strain selection, and thus will promote the healthy development of morel industry.

Optimizing the DO-stat protocol for enhanced production of thermostable pullulanase in Escherichia coli by using oxygen control strategies.

Production of a thermostable pullulanase by DO-stat fed-batch fermentation of recombinant Escherichia coli BL 21 was investigated in a 5 L of fermentor. The effect of three oxygen control strategies, glucose feedback, shifting fermentor pressure, and adding oxygen-enriched air, on cell growth and pullulanase expression were examined. The oxygen-transfer capacity was found to be enhanced with increasing fermentor pressure and oxygen ratio in oxygen-enriched air, but the cell growth and pullulanase production were restrained under high fermentor pressure. The highest cell density and pullulanase activity reached 55.1 g/L and 412 U/mL, respectively, in the case by adding oxygen-enriched air, which was suggested as an effective approach to enhance both cell growth and pullulanase production. PRACTICAL APPLICATIONS: This thermostable pullulanase displayed optimal activity at 90°C and pH 5.4, which could be applied for one-step saccharification of starch biomass. The optimization of the DO-stat fed-batch fermentation in high cell density level would provide a research basis for its industrialization.

Characterization and Antioxidant Activity of a Low-Molecular-Weight Xanthan Gum.

In the present work, a low-molecular-weight xanthan gum (LW-XG) was successfully obtained via biodegradation of commercial xanthan by the endophytic fungus Chaetomiumglobosum CGMCC 6882. The monosaccharide composition of LW-XG was glucose, mannose, and glucuronic acid in a molar ratio of 1.63:1.5:1.0. The molecular weight of LW-XG was 4.07 × 104 Da and much smaller than that of commercial xanthan (2.95 × 106 Da). Antioxidant assays showed that LW-XG had a good scavenging ability on DPPH radicals, superoxide anions, and hydroxyl radicals and good ferric reducing power. Moreover, LW-XG exhibited excellent protective effect on H2O2-injured Caco-2 cells. Results of this work suggested that LW-XG could be used in foods or pharmaceuticals to alleviate and resist the oxidative damage induced by the overproduction of reactive oxygen species.

Hybrid mesoporous silica nanospheres modified by poly (NIPAM-co-AA) for drug delivery.

The synthesis of drug delivery systems based on surface-modified mesoporous silica hollow structures remains a huge challenge. In this paper, we have obtained hollow mesoporous silica nanoparticles (MSNs) by surfactant directed sol-gel assisted hydrothermal treatment. The MSNs have the inorganic-organic hybrid frameworks with uniform diameter distribution (260 nm), and their specific surface area, mesoporous size and pore volume are 540 m2 g-1, 3.7 nm, 0.58 cm3 g-1, respectively. It was proved that the preparation of hollow ethane-bridged nanospheres with two silicon source was due to the high crosslinking of the silicone interface and hydrothermal treatment, providing a new approach for the study of drug-loaded and controlled release behavior. Based on the synthesis of MSNs, MSNs were modified by methacryloxy propyl trimethoxyl silane (MPS) on the surface of MSNs. Then N-isopropylacryamide (NIPAM) and acrylic acid (AA) were grafted onto the surface of modified MSNs. The hollow ethane-bridged PNA-MSNs (poly (NIPAM-co-acrylic acid)-MSNs) with two silicon source were prepared successfully. Due to their distinctive hollow structure, PNA-MSNs demonstrated high drug encapsulation efficiency (70.4% ± 2.9%). The experiment results proved that the modified hollow nanoparticles not only had good biocompatibility and stability, but also possessed pH-/thermal-dual responsiveness in drug release.

Glomerulonephritis triggered by chronical aortic graft infection in a male with Loeys-Dietz syndrome: A case report.

RATIONALE: Glomerulonephritis triggered by a chronically infected graft is increasingly identified because of widely used implanted device. Removal of the aortic graft and sustained antibiotic therapy is the usual approach to maximize the chance of renal recovery, but as this case shows graft removal is not always possible. PATIENT CONCERNS: A 35-year-old man with intractable and recurrent fever had acute renal failure in sustained antibiotic therapy. DIAGNOSES: Renal biopsy suggested crescentic glomerulonephritis. fluorodeoxyglucose/positron emission tomography-computed tomography showed increased metabolic activity at the site of aortic graft, reminding that chronic infection of an implanted graft can lead to severe glomerulonephritis. TGFBR2 c.1133G>T mutation was observed in mutation analysis, which was reported to be associated with Loeys-Dietz syndrome. INTERVENTIONS: Although infection was properly controlled with appropriate antimicrobial treatment, his renal dysfunction did not improve. A short-term inclusion of low-dose corticosteroid significantly benefit without introducing harm. OUTCOMES: He partly recovered from renal injury. LESSONS: In patients with glomerulonephritis triggered by a long-duration infection, low-dose corticosteroid therapy may be considered when renal dysfunction secondary to nephritis does not improve after appropriate antimicrobial treatment.

Formation of enzymatic/redox-switching nanogates on mesoporous silica nanoparticles for anticancer drug delivery.

In this study, we demonstrate a simple approach to developing mesoporous nanohybrids via a process of pre-loading of an anticancer drug (doxorubicin, DOX) into mesoporous silica nanoparticles (MSN), followed by assembly with a kind of naturally-derived polymer (gelatin, cleavable by matrix metalloproteinase 2 overexpressed by tumor). The gelatin shell is then in situ crosslinked by degradable N,N'-bis(acryloyl)cystamine (BAC) to form enzymatic and redox switchable nanogates on the mesoporous nanoparticles. The nanohybrids displayed pH/redox/enzymatic sensitivity in DOX release under conditions mimicking tumor microenvironments. The nanocarriers can be effectively taken up by A549 cells (a carcinomic human alveolar basal epithelial cell line), resulting in a high DOX intracellular accumulation and an improved anticancer cytotoxicity when compared with free DOX, suggesting their potential as a nanoplatform for therapeutic delivery.

Comparative transcriptomics reveals potential genes involved in the vegetative growth of Morchella importuna.

True morels (Morchella spp.) are edible, medicinal mushrooms which have recently been artificially cultivated in China but stable production remains a problem. Here, we describe complete and comprehensive transcriptome of Morchella importuna at the stages of vegetative mycelium (VM), initial sclerotium (IS) and mature sclerotium (MS) by deep transcriptional sequencing and de novo assembly for the first time and which will potentially provide useful information for improving its cultivation. A total of 26,496 genes were identified with a contig N50 length of 1763 bp and an average length of over 1064 bp. Additionally, 11,957 open reading frames (ORFs) were predicted and 9676 of them (80.9%) were annotated. The 2605 differentially expressed genes (DEGs) identified by gene expression clustering were mainly involved with energy metabolism and could be divided into three broad clusters, of which genes in cluster_1 and cluster_2 were involved in the metabolic process of carbohydrate, polysaccharide, hydrolase, caprolactam, beta-galactosidase, and disaccharide, respectively. Genes in cluster_3 were the largest category, mainly identified with the catalytic activity and transporter activity. Overall, the enzymes involved in the carbohydrate metabolism were highly expressed, and the CAZyme (carbohydrate-active enzyme) genes were significantly expressed within cluster_3. For expression verification, 16 CAZYme genes were selected for qRT-PCR, and the results suggested that the catabolism of carbohydrates occurs mainly in the vegetative mycelium stage, and the anabolism of the energy-rich substances is the main event of mycelial growth and sclerotial morphogenesis of M. importuna.

Preparation of thermo/redox/pH-stimulative poly(N-isopropylacrylamide-co-N,N'-dimethylaminoethyl methacrylate) nanogels and their DOX release behaviors.

Stimuli-sensitive drug delivery systems show beneficial features of both medical and pharmaceutical fields. In this article, polymeric nanogel P (N-isopropylacrylamide-N,N '-dimethylaminoethyl methacrylate [NIPAM-DMAEMA]) (PND) with pH/redox/thermo-responsivenesses was synthesized by the in situ polymerization of NIPAM and DMAEMA for the controlled release of doxorubicin hydrochloride (DOX) and N,N '-bis(acryloyl)cystamine (BAC) and N,N '-methylenebisacrylamide (MBA) act as the crosslinkers, respectively. The structure, size, and zeta potential of PND-BAC and PND-MBA were further characterized. Moreover, after loading DOX, the encapsulation efficiency and the in vitro release behavior of PND-BAC/DOX and PND-MBA/DOX nanogels were discussed in detail. Compared to PND-MBA NGs, PND-BAC nanogels have redox degradability due to the presence of the crosslinker BAC. After loading DOX, the PND-BAC/DOX nanogel showed a higher encapsulation efficiency (81.6 ± 1.2)% and thermo- and pH-responsiveness as well as redox-responsive in vitro release. These properties together with excellent environmentally sensitive properties make PND-BAC as an attractive candidate for application in drug nanocarriers for the targeted drug delivery of model payloads. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1195-1203, 2019.