Androgen deprivation therapy (ADT), including enzalutamide, induces resistance in prostate cancer; ADT resistance is associated with neuroendocrine differentiation (NED) and tumor-associated ...macrophages (TAM). This study aimed to investigate the association between enzalutamide-induced NED and TAMs and its mechanism.
The association between enzalutamide-induced NED and TAMs was investigated by IHC using prostate cancer tissues, enzalutamide-resistant mouse xenografts, and a coculture system. The underlying mechanisms were assessed using
cytokine antibody arrays, ELISAs, chromatin immunoprecipitation, and other methods. An orthotopic prostate cancer mouse model was established to evaluate the
effects of combined IL6 receptor (IL6R) and high mobility group box 1 (HMGB1) inhibition on enzalutamide resistance.
High CD163 expression was observed in ADT-treated prostate cancer or castration-resistant prostate cancer (CRPC) tissues with high levels of neuron-specific enolase (NSE) and chromogranin A (CHGA) and in enzalutamide-resistant xenografts, indicating the crucial roles of NED and TAMs in enzalutamide resistance. Specifically, enzalutamide-induced HMGB1 expression facilitated TAM recruitment and polarization and drove NED via β-catenin stabilization. HMGB1-activated TAMs secreted IL6 to augment enzalutamide-induced NED and directly promote HMGB1 transcription via STAT3. Finally, inhibition of the IL6/STAT3 pathway by tocilizumab combined with HMGB1 knockdown inhibited enzalutamide-induced resistance in an orthotopic prostate cancer mouse model.
Enzalutamide elevates HMGB1 levels, which recruits and activates TAMs. Moreover, IL6 secreted by HMGB1-activated TAMs facilitates the enzalutamide-induced NED of prostate cancer, forming a positive feedback loop between NED in prostate cancer and TAMs. The combined inhibition of IL6R and HMGB1 may serve as a new treatment for enzalutamide resistance in patients with advanced or metastatic prostate cancer.
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Coelomycete is a general term used for asexual fungi which produce conidia in fruiting bodies: pycnidial, acervular, cupulate, pycnothyria or stromatic conidiomata. The group contains numerous plant ...pathogenic, saprobic and endophytic species associated with a wide range of hosts. Traditionally, morphological characters and host associations have been used as criteria to identify and classify coelomycetes, and this has resulted in a poor understanding of their generic and species boundaries. DNA based taxonomic studies have provided a better outlook of the phylogenetic and evolutionary trends in coelomycetes. However, the present outcomes represent only a preliminary step towards the understanding of coelomycetes. Many genera have not been revisited since they were first described. The present study revises the classification of the hyaline-spored coelomycetes and provides a modern taxonomic framework based on both morphology and phylogeny. In total, 248 genera were investigated, of which less than 100 are known to have sequence data. Multi-locus sequence data analyses of 28S nrDNA, 18S nrDNA, ITS, RNA polymerase II second largest subunit (
rpb2
), and part of the translation elongation factor 1-alpha gene (
tef1
) and β-tubulin (
tub2
) gene regions were analysed. As a result, three new genera and 23 new species are introduced. In addition, three new links between sexual and asexual genera are provided. There are 138 genera that lack sequence data, and these are treated as Ascomycota, genera
incertae sedis
. Line drawings and descriptions are provided based on the examination of types and fresh collections and on the literature.
For centuries,
has been used as a traditional medicine in Asian countries to prevent and treat various diseases. Numerous publications are stating that
species have a variety of beneficial medicinal ...properties, and investigations on different metabolic regulations of
species, extracts or isolated compounds have been performed both in vitro and in vivo. However, it has frequently been questioned whether
is simply a dietary supplement for health or just a useful "medication" for restorative purposes. More than 600 chemical compounds including alkaloids, meroterpenoids, nucleobases, nucleosides, polysaccharides, proteins, steroids and triterpenes were extracted and identified from
, with triterpenes serving as the primary components. In recent years,
triterpenes and other small molecular constituents have aroused the interest of chemists and pharmacologists. Meanwhile, considering the significance of the triterpene constituents in the development of new drugs, this review describes 495 compounds from 25
species published between 1984 and 2022, commenting on their source, biosynthetic pathway, identification, biological activities and biosynthesis, together with applications of advanced analytical techniques to the characterization of
triterpenoids.
Human health is the main concern related to use of crop products irrigated with contaminated irrigation sources. Present research has been conducted to explore heavy metal status of sewage and ...industrial wastewater being used up for irrigation purpose in the peri-urban areas of the district Dera Ghazi Khan which has not been explored widely before. The analysis also followed heavy metal detection in the subsequent irrigated soil and vegetables/crop plants in relation to assessment of health risk to the consumer to plan the future monitoring in this area. An unremitting boost of heavy metals into the environment from wastewater irrigation has become a global issue. These heavy metals enter the food chain and pose health assumptions to consumers upon utilization. In the present study, an investigation has been conducted to determine metal concentrations in the wastewater, soil, and different plant species. For wastewater samples, pH, total dissolved solids (TDS), electrical conductivity (EC), and selected heavy metals such as Al, As, Cr, Cu, Fe, Mn, Pb, Zn, and Ni were determined. The mean values of heavy metals in the soil samples were within the WHO/FAO safe limit, while Cr and Pb were the most frequent (100%) among the metals. However, differentiating the sites, the concentration of Cr and Cu, Ni, and Fe were elevated. The metal transfer was highly effective from soil to the growing plants i.e. brinjal, red corn, wheat, tomato, and spinach than other plant species. Among the metals, Cr, Ni, Mn, and Pb in plant samples were exceeding the WHO/FAO safe limit. Health risk index (HRI) have revealed the possible potential risk of heavy metal contaminated plant species in the order of spinach (6.4) > wheat (6.4) > brinjal (5.9) > tomato (4.7) > red corn (4.5) > apple gourd (4.3) > white corn (3.8) > cabbage (3.1) > luffa (2.9). Likewise, HRI of different metals was calculated as Cu (19.6) > Zn (17.9) > Cr (2.95) > Ni (0.85) > Mn (0.48) > Fe (0.15) > Cd (0.11) > Pb (0.05) > As (0.00001). The level of HRI through the use of dietary plants revealed an elevated risk level than the acceptable limit (HRI > 1) for Cu > Zn > Cr in adults. Our findings suggest that there would be a serious health risk to the consumers due to the consumption of these plant species being irrigated with the wastewater. Therefore, a strict regulatory mechanism is proposed for the safety of food plants in the study area including monitoring and recycling of crop plants, and building water treatment plants to remove pollutants and clean wastewater.
The type specimens of
Auerswaldia
,
Auerswaldiella
,
Barriopsis
,
Botryosphaeria
,
Leptoguignardia
,
Melanops
,
Neodeightonia
,
Phaeobotryon, Phaeobotryosphaeria, Phyllachorella, Pyrenostigme, ...Saccharata
,
Sivanesania
,
Spencermartinsia
and
Vestergrenia
were examined and fresh specimens of
Botryosphaeriales
were collected from Thailand. This material is used to provide a systematic treatment of
Botryosphaeriales
based on morphology and phylogeny. Two new genera,
Botryobambusa
and
Cophinforma
are introduced and compared with existing genera. Four species new to science,
Auerswaldia dothiorella
,
A. lignicola
,
Botryosphaeria fusispora
and
Phaeobotryosphaeria eucalypti,
are also described and justified. We accept 29 genera in
Botryosphaeriales
, with
Macrovalsaria
being newly placed. In the phylogenetic tree, the 114 strains of
Botyrosphaeriales
included in the analysis cluster into two major clades with 80 %, 96 % and 1.00 (MP, ML and BY) support, with Clade A containing the family type of
Botryosphaeriaceae
, and Clade B containing
Phyllosticta
,
Saccharata
and
Melanops
species. This group may represent
Phyllostictaceae
. In Clade A the taxa analyzed cluster in eight sub-clades (Clades A1–8). Clade A1 comprises three distinct subclusters corresponding to the genera
Diplodia
(
Diplodia
Clade),
Neodeightonia
(
Neodeightonia
Clade) and
Lasiodiplodia
(
Lasiodiplodia
Clade)
.
Clade A2 clusters into three groups representing
Phaeobotryosphaeria
(100 %)
, Phaeobotryon
(100 %) and
Barriopsis
(94 %). Clade A3 incorporates 17 strains that cluster into three well-supported genera (
Dothiorella
(86 %),
Spencermartinsia
(100 %) and
Auerswaldia
(63 %); the position of
Macrophomina
is not stable. Clade A4 is a single lineage (100 %) representing the new genus
Botryobambusa
. Clade A5 is a well-supported subclade incorporating
Neofussicoccum
. Clade A6 represents the type species of
Botryosphaeria
, three other
Botryosphaeria
species and two other genera,
Neoscytalidium
and
Cophinforma
gen. nov. Clade A7 comprises two
Pseudofusicoccum
species and Clade A8 has two
Aplosporella
species. These sub-clades may eventually require separate families but this requires analysis of a much larger dataset. Our data advances the understanding of
Botryosphaeriales,
there is, however, still much research to be carried out with resolution of families and genera, linkage of sexual and asexual morphs and differentiation of cryptic species.
Mangoes belong to Mangifera (Anacardiaceae), which contains 69 species, but only Mangifera indica is popularly cultivated and commercialized. Mango is one of the most important crops grown in China’s ...Yunnan Province and significantly contributes to the economic security of these locals. Endophytic fungi have been recognized as beneficial microbes that improve plant growth, productivity, and survivability under environmental stress. Nevertheless, many host plant-related endophytic fungi are yet to be identified, including the mango-related species. During this study, we recognized three different fungal species in the family Chaetomiaceae derived from healthy mango (Mangifera indica) leaves based on morphological examinations coupled with multi-gene phylogenetic analysis (ITS, LSU, rpb2, and tub2). These species are Dichotomopilus funicola (KUNCC23-13347) and Humicola wallefii (KUNCC22-10759, 23-13348), derived from new hosts, and a new species of Arcopilus hongheensis (KUNCC22-10767, 23-13346).
Malnutrition is mainly caused by iron and zinc micronutrient deficiencies affecting about half of the world's population across the globe. Biofortification of staple crops is the right approach to ...overcome malnutrition and enhance nutrient contents in the daily food of humans. This study aimed to evaluate the role of foliar application of iron and zinc in
Trichoderma harzianum
treated soil on various growth characteristics, quality, and yield of wheat varieties. Plants were examined in the absence/presence of
T. harzianum
, and iron and zinc micronutrients in both optimal and high-stress conditions. Although the symbiotic association of
T. harzianum
and common wheat is utilized as an effective approach for wheat improvement because of the dynamic growth promoting the ability of the fungus, this association was found tremendously effective in the presence of foliar feeding of micronutrients for the enhancement of various growth parameters and quality of wheat. The utilization of this approach positively increased various growth parameters including spike length, grain mass, biomass, harvest index, and photosynthetic pigments. The beneficial role of
T. harzianum
in combination with zinc and iron in stimulating plant growth and its positive impact on the intensities of high molecular weight glutenin subunits (HMW-GS) alleles make it an interesting approach for application in eco-friendly agricultural systems. Further, this study suggests a possible alternative way that does not merely enhances the wheat yield but also its quality through proper biofortification of iron and zinc to fulfill the daily needs of micronutrients in staple food.
By nature, a traditional attack method, denial-of-service (DDoS) attack poses a considerable threat to the security of the blockchain network layer. This paper proposes a distributed DDoS-attack ...traffic detection method based on a cross multilayer convolutional neural network model in the blockchain network layer. The method resolves the low generalisation, high misreporting rate, and low detection efficiency problems of the existing detection methods, which are caused by nondistinctive core features and the high complexity of robust features when detecting DDoS attacks transmitted by mixed protocols on a blockchain network layer. First, the model performs a convolution operation on preprocessed traffic on the blockchain network layer using a cross-layer method based on L2 regularisation. After this operation, the model can perceive the detailed features of attack traffic from multiple levels while enhancing the representational performance of key features; specifically, the parameters with high-variance terms are penalised to limit changes in the model’s weight parameters. The highly robust abstract features of attack traffic are extracted, thereby increasing the generalisation ability and reducing the misreporting rate of the model. Second, parametric encoding of the abstract features is performed by a stacked sparse autoencoder based on Kullback–Leibler divergence, and the sparsity of the model is adjusted to reduce the redundant data and the coupling between abstract features. The outputs of the encoded features are then effectively categorised. Finally, the global optimisation of parameters is performed by an improved random gradient-descent algorithm, which prevents oscillation of the training parameters and accelerates the model convergence. In an experimental evaluation, the proposed method achieved satisfactory binary- and multiclass detection of DDoS-attack traffic on both CSE-CIC-IDS 2018 on the AWS dataset and on the real mixed data of a blockchain network layer.
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