DNA Damage Inducer Mitoxantrone Amplifies Synergistic Mild-Photothermal Chemotherapy for TNBC via Decreasing Heat Shock Protein 70 Expression.

Patients with triple-negative breast cancer (TNBC) have the worst clinical outcomes when compared to other subtypes of breast cancer. Nanotechnology-assisted photothermal therapy (PTT) opens new opportunities for precise cancer treatment. However, thermoresistance caused by PTT, as well as uncertainty in the physiological metabolism of existing phototherapeutic nanoformulations, severely limit their clinical applications. Herein, based on the clinically chemotherapeutic drug mitoxantrone (MTO), a multifunctional nanoplatform (MTO-micelles) is developed to realize mutually synergistic mild-photothermal chemotherapy. MTO with excellent near-infrared absorption (≈669 nm) can function not only as a chemotherapeutic agent but also as a photothermal transduction agent with elevated photothermal conversion efficacy (ƞ = 54.62%). MTO-micelles can accumulate at the tumor site through the enhanced permeability and retention effect. Following local near-infrared irradiation, mild hyperthermia (<50 °C) assists MTO in binding tumor cell DNA, resulting in chemotherapeutic sensitization. In addition, downregulation of heat shock protein 70 (HSP70) expression due to enhanced DNA damage can in turn weaken tumor thermoresistance, boosting the efficacy of mild PTT. Both in vitro and in vivo studies indicate that MTO-micelles possess excellent synergetic tumor inhibition effects. Therefore, the mild-photothermal chemotherapy strategy based on MTO-micelles has a promising prospect in the clinical transformation of TNBC treatment.

A micelle-based stage-by-stage impelled system for efficient doxorubicin delivery.

Chemotherapy remains the mainstay of cancer treatment, benefiting millions of patients each year, but the side effects of chemotherapy drugs severely limit their clinical use. Doxorubicin (DOX) can cause various side effects such as heart damage and treatment-related tumors. The effective use of active and passive targeting will improve the clinical application of DOX. Here, TPGS3350 and bioactive peptides were utilized to construct a micelle-based stage-by-stage impelled efficient system (missiles) for DOX delivery (DOX missiles). By taking advantage of the EPR effect, DOX missiles are efficiently enriched at the tumor site. After being cleaved by matrix metalloproteinase2 (MMP2), the peptide (VRGD) targets tumor cells to facilitate uptake of the missiles by the tumor cells via receptor-mediated endocytosis. The intracellular activated caspase-3-catalyzed explosion of DOX missiles further enables efficient tumor killing. This study provides an efficient approach for DOX delivery and toxicity reduction.

Nanomedicine for T-Cell Mediated Immunotherapy.

T-cell immunotherapy offers outstanding advantages in the treatment of various diseases, and with the selection of appropriate targets, efficient disease treatment can be achieved. T-cell immunotherapy has made great progress, but clinical results show that only a small proportion of patients can benefit from T-cell immunotherapy. The extensive mechanistic work outlines a blueprint for using T cells as a new option for immunotherapy, but also presents new challenges, including the balance between different fractions of T cells, the inherent T-cell suppression patterns in the disease microenvironment, the acquired loss of targets, and the decline of T-cell viability. The diversity, flexibility, and intelligence of nanomedicines give them great potential for enhancing T-cell immunotherapy. Here, how T-cell immunotherapy strategies can be adapted with different nanomaterials to enhance therapeutic efficacy is discussed. For two different pathological states, immunosuppression and immune activation, recent advances in nanomedicines for T-cell immunotherapy in diseases such as cancers, rheumatoid arthritis, systemic lupus erythematosus, ulcerative colitis, and diabetes are summarized. With a focus on T-cell immunotherapy, this review highlights the outstanding advantages of nanomedicines in disease treatment, and helps advance one's understanding of the use of nanotechnology to enhance T-cell immunotherapy.

Dual Passivation of Perovskite and SnO2 for High-Efficiency MAPbI3 Perovskite Solar Cells.

So far, most techniques for modifying perovskite solar cells (PSCs) focus on either the perovskite or electron transport layer (ETL). For the sake of comprehensively improving device performance, a dual-functional method of simultaneously passivating trap defects in both the perovskite and ETL films is proposed that utilizes guidable transfer of Eu3+ in SnO2 to perovskite. Europium ions are distributed throughout the SnO2 film during the formation process of SnO2, and they can diffuse directionally through the SnO2/perovskite interface into the perovskite, while most of the europium ions remain at the interface. Under the synergistic effect of distributed Eu3+ in the SnO2 and aggregated Eu3+ at the interface, the electron mobilities of ETLs are evidently improved. Meanwhile, diffused Eu3+ ions passivate the perovskite to reduce trap densities at the grain boundaries, which can dramatically elevate the open-circuit voltage (V oc) of PSCs. Finally, the mainly PSCs coated on SnO2:Eu3+ ETL achieve a power conversion efficiency of 20.14%. Moreover, an unsealed device degrades by only 13% after exposure to ambient atmosphere for 84 days.

ß3-Adrenergic Activation Improves Maternal and Offspring Perinatal Outcomes in Diet-Induced Prepregnancy Obesity in Mice.

OBJECTIVE: Prepregnancy obesity is an epidemic disorder that seriously threatens both maternal and offspring health. This study investigated the effects of ß3-adrenergic receptor (ß3-AR) activation on the perinatal outcomes in a diet-induced prepregnancy obese (PPO) murine model. METHODS: Four-week-old female C57BL/6 mice were fed high-fat diet or chow diet for 16 weeks to yield PPO mice and chow-fed (CF) lean mice, respectively. After successful mating with CF males, the PPO and CF mice were both randomly divided into vehicle control- or CL316,243 (a highly selective ß3-AR agonist)-treated groups. On gestational day 7, subcutaneous infusion of CL316,243 or saline vehicle (1 mg/kg/d) was provided using osmotic pumps. The perinatal outcomes, adipose tissue morphology, and metabolic and inflammatory markers were examined. RESULTS: Chronic ß3-AR agonist infusion induced brown adipose tissue activation and white adipose tissue browning and countered obesity-induced alterations in lipid profiles, insulin resistance, and systemic and local inflammatory states. Moreover, ß3-AR activation was associated with improved placental perfusion and offspring outcomes. CONCLUSIONS: Our results provide proof-of-principle evidence that pharmacological ß3-AR activation may be of therapeutic potential in preventing prepregnancy-obesity-associated adverse maternal and offspring perinatal outcomes.

RETRACTED ARTICLE: Characterization of the complete mitochondrial genome of an important edible fungus Auricularia Polytricha.

We, the Editor, authors and Publisher of Mitochondrial DNA Part B: Resources, have retracted the following article: Qiang Li, Xin Jin, Zuqin Chen, Chuan Xiong, Ping Li & Wenli Huang (2019) 'Characterization of the complete mitochondrial genome of an important edible fungus Auricularia Polytricha' 4:1, 1107-1108, DOI https://doi.org/10.1080/23802359.2019.1586494. This article has been retracted at the request of the authors as, subsequent to publication, it has been identified that the species reported in the article is incorrect. The species should be Suillus sp. and not Auricularia polytricha as reported. The article has therefore been retracted as the data reported in the article are inaccurate. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as "Retracted".

Characterization and comparison of the mitochondrial genomes from two Lyophyllum fungal species and insights into phylogeny of Agaricomycetes.

Lyophyllum decastes and Lyophyllum shimeji are the two primary species within the L. decastes complex, and they differ considerably in their nutritional lifestyles and preferred growth environments. However, differences in their mitogenomes have not yet been investigated. In this study, the mitogenomes of the two species were sequenced by next-generation sequencing technology, successfully assembled, and compared. The two mitogenomes of L. decastes and L. shimeji comprised circular DNA molecules of sizes 50,643 bp and 73,678 bp, respectively. The lengths and base compositions of their core protein coding genes (PCGs) and tRNA genes varied considerably between the two mitogenomes. Further, gene collinearity analysis indicated a large-scale gene rearrangement between the two mitogenomes. Of the 15 core PCGs, the genetic distance of the atp9 gene was the smallest between the two species, indicating that this gene was highly conserved in the two Lyophyllum species. Phylogenetic analysis based on a combined mitochondrial gene dataset resulted in a well-supported topology, wherein the two Lyophyllum species were most closely related to Tricholoma matsutake. This study represents the first report of mitogenomes for the Lyophyllum genus. As such, the results will provide a basis for understanding the differentiation and evolution of mitogenomes in the Lyophyllum genus.

Characterization and comparative analysis of six complete mitochondrial genomes from ectomycorrhizal fungi of the Lactarius genus and phylogenetic analysis of the Agaricomycetes.

Lactarius is one of the most prominent genera of mushroom-forming fungi in the world. In the present study, complete mitochondrial genomes (mitogenomes) from six Lactarius species were sequenced and assembled. The six mitogenomes were all composed of circular DNA molecules, with total lengths ranging from 38,445 bp to 60,843 bp. The GC contents, GC skews, and AT skews of the mitogenomes varied among the six species. Mitogenomic synteny analysis revealed the presence of gene rearrangements among the mitogenomes. Among the 15 core protein coding genes (PCGs) within the mitogenomes, nad4L exhibited the least genetic distance among species, indicating a high degree of conservation. In addition, the Ka/Ks values for all 15 core PCGs were <1, suggesting that they were subject to purifying selection. Comparative analyses indicated that the increase of intron numbers and sizes contributed to the expansion of mitogenomes in Lactarius. Phylogenetic analyses based on three combined gene datasets yielded identical and well-supported (BPP ≥ 0.83) topologies, dividing the six Lactarius species into two groups. This study provides the first report of mitogenomes from Lactarius and promotes further understanding of the genetics, evolution, and phylogenetic relationships of this important ectomycorrhizal fungal genus.

The first complete mitochondrial genome from the family Hygrophoraceae (Hygrophorus russula) by next-generation sequencing and phylogenetic implications.

Hygrophorus russula (Schaeff.) Kauffman is an edible ectomycorrhizal fungus that is widely distributed in the world. In this study, the mitogenome of H. russula was sequenced and assembled. The mitogenome of H. russula is composed of circular DNA molecules, with a total size of 55,769 bp. Further analysis indicated that the frequent use of A and T in codons contributes to the high AT content (80.87%) in the H. russula mitogenome. Comparative analysis indicated that the length and base composition of the core protein-encoding genes, and the number of tRNA genes in the H. russula mitogenome varied from that of other Agaricales mitogenomes. Gene arrangement analysis revealed a novel gene order in the H. russula mitogenome. In addition, the expansion of the mitogenome in Agaricales was found to be closely related to the increase in the number of introns. Phylogenetic analysis of the combined mitochondrial gene set showed strong support for tree topologies, and H. russula was determined to be relatively distant from other Agaricales species. This study is the first report on the mitogenome of a member of genus Hygrophorus as well as family Hygrophoraceae, which improves our understanding of mitochondrial differentiation and evolution in the important ectomycorrhizal fungi Hygrophorus species.

Characterization and comparative mitogenomic analysis of six newly sequenced mitochondrial genomes from ectomycorrhizal fungi (Russula) and phylogenetic analysis of the Agaricomycetes.

In this study, the mitochondrial genomes of six Russula species were sequenced using next generation sequencing. The six mitogenomes were all composed of circular DNA molecules, with lengths ranging from 40,961 bp to 69,423 bp. The length and number of protein coding genes (PCGs), GC content, AT skew, and GC skew varied among the six mitogenomes. The increased number and total size of introns likely contributed to the size expansion of mitogenomes in some Russula species. Gene synteny analysis revealed some gene rearrangements among the six mitochondrial genomes. The nad4L gene had the lowest K2P genetic distance of the 15 core PCGs among the six Russula species, indicating that this gene was highly conserved. The Ka/Ks values for all 15 core PCGs were <1, suggesting that they were all subject to purifying selection. Phylogenetic analyses based on two gene datasets (15 core PCGs, and 15 core PCGs + rnl + rns) recovered identical and well-supported trees. In addition, cox1 was identified as a potential single-gene molecular marker for the phylogenetic analysis of relationships among Agaricomycetes species. This study provides the first report of mitogenomes from the Russulaceae family and facilitates the investigation of population genetics and evolution of other ectomycorrhizal fungi.

Characterization of the mitochondrial genomes of three species in the ectomycorrhizal genus Cantharellus and phylogeny of Agaricomycetes.

Cantharellus is a large ectomycorrhizal genus. Here, we assembled and annotated the mitochondrial genomes of C. lutescens, C. appalachiensis, and two specimens of C. cibarius. We found that all four mitochondrial genomes were circular and between 56,786 bp and 80,736 bp, long. The length and GC content of the protein-coding genes (PCGs) in the four mitogenomes varied. All tRNAs were folded into classical cloverleaf secondary structures; 16 of the 26 identified tRNAs contained variable sites across Cantharellus genus. C. appalachiensis was found containing the most repeated sequences (11.32% of the mitogenome), along with a substantial number of gene rearrangements. Comparative analysis of three C. cibarius specimens indicated that the mitogenomes of specimens from different regions differed. The Ka/Ks ratios of all 15 PCGs identified across all four mitogenomes were <1, indicating that these genes have been subject to purifying selection. Phylogenetic analysis recovered a well-supported tree based on a combined analysis of the 15 PCGs. In addition, we identified cob, cox1, and rnl as potential single-gene markers for the analysis of phylogenetic relationships among Agaricomycetes species. The mitogenomes reported in this study will facilitate the study of population genetics and evolution in Cantharellus and other closely related species.

Comparative mitogenomics reveals large-scale gene rearrangements in the mitochondrial genome of two Pleurotus species.

In the present study, we assembled the mitogenomes of Pleurotus citrinopileatus and Pleurotus platypus. The circular mitogenome of the two Pleurotus species comprises a set of 14 conserved protein-encoding genes (PEGs), 2 RNA genes (small subunit ribosomal RNA and large subunit ribosomal RNA), and 24 tRNAs, with sizes of 60,694 and 73,807 bp, respectively. They contain 4 and 10 introns with 3 and 10 intronic open reading frames (ORFs), respectively. Thirteen position classes (Pcls) of introns were found in the cox1 gene of four Pleurotus species. The number and class of Pcl varied among different Pleurotus species, indicating that numerous events of loss and gain occurred during evolution of Pleurotus. Comparative mitogenomic and collinearity analyses reveal that large-scale gene rearrangements may have occurred during the evolution of Pleurotus citrinopileatus and Pleurotus platypus, including gene rearrangements and inversions, which may be related to the observed high amounts of repetitive DNA elements (5.62 and 5.45%, respectively). Phylogenetic analysis based on concatenated mitochondrial protein sequences reveals that concatenated mitochondrial genes are suitable as molecular markers for phylogenetic analysis. This serves as the first report on large-scale rearrangements in the mitochondria of the genus Pleurotus, thereby improving our understanding of the evolution of the Pleurotus genus and other macrofungi.

In vitro Antimicrobial Activities and Mechanism of 1-Octen-3-ol against Food-related Bacteria and Pathogenic Fungi.

1-Octen-3-ol, known as mushroom alcohol, is a natural product extracted from fungi and plants. Its antimicrobial activities against five common food-related bacteria and two pathogenic fungi were evaluated in this paper, including Staphylococcus aureus, Bacillus subtilis, Staphylococcus epidermidis, Escherichia coli, Pseudomonas aeruginosa, Fusarium tricinctum and Fusarium oxysporum. The results showed that 1-octen-3-ol had a strong antibacterial activity against the tested bacteria, especially against Gram-positive bacteria, and it can also inhibit fungal growth and spore germination. The minimum inhibitory concentrations (MICs) for Gram-positive bacteria and Gram-negative bacteria were 1.0 and 2.0 mg/mL, respectively. The minimum bactericidal concentrations (MBCs) for Gram-positive bacteria and Gram-negative bacteria were 4.0 and 8.0 mg/mL, respectively. The completely inhibitory concentrations for fungal growth and spore germination were 8.0 and 2.0 mg/ml, respectively. Cell constituents' leakage and scanning electron microscope assays indicated that 1-octen-3-ol changed the permeability of the cell membrane. Discrepant antimicrobial activity between 1-octen-3-ol and 1-octen-3-one indicated that hydroxyl may play a decisive role in antimicrobial activity. It is suggested that 1-octen-3-ol, with attractive mushroom aroma and antimicrobial activity, has potential applications in control of pathogens.

Tuber indicum shapes the microbial communities of ectomycorhizosphere soil and ectomycorrhizae of an indigenous tree (Pinus armandii).

The aim of this study was to investigate the effect of an ectomycorrhizal fungus (Tuber indicum) on the diversity of microbial communities associated with an indigenous tree, Pinus armandii, and the microbial communities in the surrounding ectomycorhizosphere soil. High-throughput sequencing was used to analyze the richness of microbial communities in the roots or rhizosphere of treatments with or without ectomycorrhizae. The results indicated that the bacterial diversity of ectomycorhizosphere soil was significantly lower compared with the control soil. Presumably, the dominance of truffle mycelia in ectomycorhizosphere soil (80.91%) and ectomycorrhizae (97.64%) was the main factor that resulted in lower diversity and abundance of endophytic pathogenic fungi, including Fusarium, Monographella, Ustilago and Rhizopus and other competitive mycorrhizal fungi, such as Amanita, Lactarius and Boletus. Bacterial genera Reyranena, Rhizomicrobium, Nordella, Pseudomonas and fungal genera, Cuphophyllus, Leucangium, Histoplasma were significantly more abundant in ectomycorrhizosphere soil and ectomycorrhizae. Hierarchical cluster analysis of the similarities between rhizosphere and ectomycorrhizosphere soil based on the soil properties differed significantly, indicating the mycorrhizal synthesis may have a feedback effect on soil properties. Meanwhile, some soil properties were significantly correlated with bacterial and fungal diversity in the rhizosphere or root tips. Overall, this work illustrates the interactive network that exists among ectomycorrhizal fungi, soil properties and microbial communities associated with the host plant and furthers our understanding of the ecology and cultivation of T. indicum.

The potential neuritogenic activity of aqueous extracts from Morchella importuna in rat pheochromocytoma cells.

The aim of this study was to explore the neuritogenic effects of aqueous extracts from the fruiting bodies of Morchella importuna (MEA). 3-(4, 5-dimethythiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay was carried out to assess the cytotoxicity of MEA. Neurite outgrowth stimulation assay was used to evaluate the potentiation of neuritogenic activity induced by MEA. The specific inhibitors for TrkA, MEK/ERK and PI3K signaling pathway were served to clarify the mechanism of MEA's neuritogenic effects. It was shown that MEA could mimic neuritogenic activity of NGF, a kind of representative neurotrophic factors with no significant cytotoxicity, and stimulate neurite outgrowth in a dose-dependent manner of PC12 cells. The neuritogenic activity induced by MEA required activity of PI3K/Akt and MEK/ERK1/2 signaling pathways, as well as parts of TrkA receptor. Accordingly, MEA could be used as a promising neuritogenic-stimulation compound for nervous diseases treatment.

Neuroprotective effect of crude polysaccharide isolated from the fruiting bodies of Morchella importuna against H2O2-induced PC12 cell cytotoxicity by reducing oxidative stress.

Oxidative stress played an essential role in neuronal cell injury through several apoptotic mechanisms associated with many neurodegenerative diseases. Reducing oxidative stress through antioxidants might be a possible strategy that could retard the disease's progression. In order to investigate the neuroprotective role of MIP (the crude polysaccharide extracted from the fruiting bodies of Morchella importuna), the antioxidative activity of MIP against the H2O2-induced cytotoxicity and the underlying preventative mechanisms in rat pheochromocytoma (PC12) cells were illustrated. It was shown that MIP could considerably enhance the viability of PC12 cells exposure to H2O2 and increased the activities of antioxidant enzyme like CAT, GSH-Px and SOD. It also reduced the content of malondialdehyde MDA and caspase-3 activation. In addition, MIP inhibited cell apoptosis via down-regulation of the NF-κB pathway and the p38-JNK pathway as well as activating of the extracellular signal-regulated kinase (ERK). Accordingly, MIP can be used as a promising neuroprotective compound for nervous diseases treatment.

Prevalence and molecular characterization of Cryptosporidium in giant panda (Ailuropoda melanoleuca) in Sichuan province, China.

BACKGROUND: Cryptosporidium spp. have been extensively reported to cause significant diarrheal disease in humans and domestic animals. On the contrary, little information is available on the prevalence and characterization of Cryptosporidium in wild animals in China, especially in giant pandas. The aim of the present study was to detect Cryptosporidium infections and identify Cryptosporidium species at the molecular level in both captive and wild giant pandas in Sichuan province, China. FINDINGS: Using a PCR approach, we amplified and sequenced the 18S rRNA gene from 322 giant pandas fecal samples (122 from 122 captive individuals and 200 collected from four habitats) in Sichuan province, China. The Cryptosporidium species/genotypes were identified via a BLAST comparison against published Cryptosporidium sequences available in GenBank followed by phylogenetic analysis. The results revealed that both captive and wild giant pandas were infected with a single Cryptosporidium species, C. andersoni, at a prevalence of 15.6% (19/122) and 0.5% (1/200) in captive and wild giant pandas, respectively. CONCLUSIONS: The present study revealed the existence of C. andersoni in both captive and wild giant panda fecal samples for the first time, and also provided useful fundamental data for further research on the molecular epidemiology and control of Cryptosporidium infection in giant pandas.

Prevalence of Cryptosporidium infection in captive lesser panda (Ailurus fulgens) in China.

Cryptosporidium is a global epidemic parasite and one of the most important intestinal pathogens causing diarrhea in animals and humans. Despite extensive research on this parasite group, little is known about rates of Cryptosporidium infection in lesser pandas. In this study, we use molecular diagnostic tools to detect Cryptosporidium infections and identify Cryptosporidium species in the lesser panda. Using a PCR approach, we sequenced the 18S rRNA gene in fecal samples collected from 110 captive lesser pandas held throughout China (approximately one third of the captive population). We determined Cryptosporidium species via a BLAST comparison of our sequences against those of published Cryptosporidium sequences available in GenBank and subsequent phylogenetic analysis. We report that captive lesser pandas were infected with a single Cryptosporidium species, Cryptosporidium andersoni, at a prevalence of 6.36 % (7/110). The present investigation revealed the existence of C. andersoni infection in captive lesser panda and suggested that proper control measures should be taken carefully to protect the welfare of zoo workers and visitors.

Expression of the Tpanxb1 gene from Taenia pisiformis and its potential diagnostic value by dot-ELISA.

Cysticercosis, caused by the larvae of Taenia pisiformis, is a common disease in rabbits that results in economic losses. To date, there has been limited information available on the early detection of infection by this parasite. This study describes a dot-ELISA method based on an autologous antigen annexin B1 (Tpanxb1). Its potential for serodiagnosis of rabbit cysticercosis was also evaluated. Western blot analysis revealed that the recombinant Tpanxb1 (rTpanxb1) protein could be specifically recognized by rabbit anti-sera. In serum trials, the antibodies could be detected by dot-ELISA using rTpanxb1 at 14 days post-infection. The positive response was present for up to 49 days post-infection. Based on the necropsy results of 169 rabbit samples, the relative sensitivity and specificity of the dot-ELISA were 94.55% and 92.86%, respectively. This study provides a foundation for studying the immunological function of annexin and its application to control Taenia cestodes.