Elucidation of the ferrichrome siderophore biosynthetic pathway in albomycin-producing Streptomyces sp. ATCC 700974.

Sideromycins are a unique subset of siderophores comprising of a siderophore conjugated to an antimicrobial agent. The "Trojan horse" antibiotic albomycins are unique sideromycins consisting of a ferrichrome-type siderophore conjugated to a peptidyl nucleoside antibiotic. They exhibit potent antibacterial activities against many model bacteria and a number of clinical pathogens. Earlier studies have provided significant insight into the biosynthetic pathway of the peptidyl nucleoside moiety. We herein decipher the biosynthetic pathway of the ferrichrome-type siderophore in Streptomyces sp. ATCC 700974. Our genetic studies suggested that abmA, abmB, and abmQ are involved in the formation of the ferrichrome-type siderophore. Additionally, we performed biochemical studies to demonstrate that a flavin-dependent monooxygenase AbmB and an N-acyltransferase AbmA catalyze sequential modifications of L-ornithine to generate N5-acetyl-N5-hydroxyornithine. Three molecules of N5-acetyl-N5-hydroxyornithine are then assembled to generate the tripeptide ferrichrome through the action of a nonribosomal peptide synthetase AbmQ. Of special note, we found out that orf05026 and orf03299, two genes scattered elsewhere in the chromosome of Streptomyces sp. ATCC 700974, have functional redundancy for abmA and abmB, respectively. Interestingly, both orf05026 and orf03299 are situated within gene clusters encoding putative siderophores. In summary, this study provided new insight into the siderophore moiety of albomycin biosynthesis and shed light on the contingency of multiple siderophores in albomycin-producing Streptomyces sp. ATCC 700974.

Environmental enrichment alleviates hyperalgesia by modulating central sensitization in a nitroglycerin-induced chronic migraine model of mice.

BACKGROUND: Chronic migraine (CM) is a debilitating neurofunctional disorder primarily affecting females, characterized by central sensitization. Central sensitization refers to the enhanced response to sensory stimulation, which involves changes in neuronal excitability, synaptic plasticity, and neurotransmitter release. Environmental enrichment (EE) can increase the movement, exploration, socialization and other behaviors of mice. EE has shown promising effects in various neurological disorders, but its impact on CM and the underlying mechanism remains poorly understood. Therefore, the purpose of this study was to determine whether EE has the potential to serve as a cost-effective intervention strategy for CM. METHODS: A mouse CM model was successfully established by repeated administration of nitroglycerin (NTG). We selected adult female mice around 8 weeks old, exposed them to EE for 2 months, and then induced the CM model. Nociceptive threshold tests were measured using Von Frey filaments and a hot plate. The expression of c-Fos, calcitonin gene-related peptide (CGRP) and inflammatory response were measured using WB and immunofluorescence to evaluate central sensitization. RNA sequencing was used to find differentially expressed genes and signaling pathways. Finally, the expression of the target differential gene was investigated. RESULTS: Repeated administration of NTG can induce hyperalgesia in female mice and increase the expression of c-Fos and CGRP in the trigeminal nucleus caudalis (TNC). Early exposure of mice to EE reduced NTG-induced hyperalgesia in CM mice. WB and immunofluorescence revealed that EE inhibited the overexpression of c-Fos and CGRP in the TNC of CM mice and alleviated the inflammatory response of microglia activation. RNA sequencing analysis identified that several central sensitization-related signaling pathways were altered by EE. VGluT1, a key gene involved in behavior, internal stimulus response, and ion channel activity, was found to be downregulated in mice exposed to EE. CONCLUSION: EE can significantly ameliorate hyperalgesia in the NTG-induced CM model. The mechanisms may be to modulate central sensitization by reducing the expression of CGRP, attenuating the inflammatory response, and downregulating the expression of VGluT1, etc., suggesting that EE can serve as an effective preventive strategy for CM.

A c-Fos activation map in nitroglycerin/levcromakalim-induced models of migraine.

BACKGROUND: Chronic migraine is a common and highly disabling disorder. Functional MRI has indicated that abnormal brain region activation is linked with chronic migraine. Drugs targeting the calcitonin gene-related peptide (CGRP) or its receptor have been reported to be efficient for treating chronic migraine. The CGRP signaling was also shared in two types of chronic migraine models (CMMs). However, it remains unclear whether the activation of specific brain regions could contribute to persistent behavioral sensitization, and CGRP receptor antagonists relieve migraine-like pain in CMMs by altering specific brain region activation. Therefore, it's of great interest to investigate brain activation pattern and the effect of olcegepant (a CGRP receptor-specific antagonist) treatment on alleviating hyperalgesia by altering brain activation in two CMMs, and provide a reference for future research on neural circuits. METHODS: Repeated administration of nitroglycerin (NTG) or levcromakalim (LEV) was conducted to stimulate human migraine-like pain and establish two types of CMMs in mice. Mechanical hypersensitivity was evaluated by using the von Frey filament test. Then, we evaluated the activation of different brain regions with c-Fos and NeuN staining. Olcegepant was administered to explore its effect on mechanical hyperalgesia and brain region activation. RESULTS: In two CMMs, acute and basal mechanical hyperalgesia was observed, and olcegepant alleviated mechanical hyperalgesia. In the NTG-induced CMM, the medial prefrontal cortex (mPFC), anterior cingulate cortex (ACC), and the caudal part of the spinal trigeminal nucleus (Sp5c) showed a significant increase of c-Fos expression in the NTG group (p < 0.05), while pre-treatment with olcegepant reduced c-Fos expression compared with NTG group (p < 0.05). No significant difference of c-Fos expression was found in the paraventricular thalamic nucleus (PVT) and ventrolateral periaqueductal gray (vlPAG) between the vehicle control and NTG group (p > 0.05). In the LEV-induced CMM, mPFC, PVT, and Sp5c showed a significant increase of c-Fos expression between vehicle control and LEV group, and olcegepant reduced c-Fos expression (p < 0.05). No significant difference in c-Fos expression was found in vlPAG and ACC (p > 0.05). CONCLUSIONS: Our study demonstrated the activation of mPFC and Sp5c in two CMMs. Olcegepant may alleviate hyperalgesia of the hind paw and periorbital area by attenuating brain activation in CMMs.

Stepwise increase of thaxtomins production in Streptomyces albidoflavus J1074 through combinatorial metabolic engineering.

Herbicide-resistance in weeds has become a serious threat to agriculture across the world. Thus, there is an urgent need for the discovery and development of herbicides with new modes of action. Thaxtomin phytotoxins are a group of nitrated diketopiperazines produced by potato common scab-causing phytopathogen Streptomyces scabies and other actinobacterial pathogens. They are generally considered to function as inhibitors of cellulose synthesis in plants, and thus have great potential to be used as natural herbicides. Generation of an overproducing strain is crucial for the scale-up production of thaxtomins and their wide use in agriculture. In the present study, we employed a stepwise strategy by combining heterologous expression, repressor deletion, activator overexpression, and optimization of fermentation media for high-level production of thaxtomins. The maximum yield of 728 mg/L thaxtomins was achieved with engineered Streptomyces albidoflavus J1074 strains in shake-flask cultures, and it was approximately 36-fold higher than S. albidoflavus J1074 carrying the unmodified cluster. Moreover, the yield of thaxtomins could reach 1973 mg/L when the engineered strain was cultivated in a small-scale stirred-tank bioreactor. This is the highest titer reported to date, representing a significant leap forward for the scale-up production of thaxtomins. Our study presents a robust, easy-to-use system that will be broadly useful for improving titers of bioactive compounds in many Streptomyces species.

Dual effects of targeting S100A11 on suppressing cellular metastatic properties and sensitizing drug response in gastric cancer.

BACKGROUND: S100A11 is a member of the S100 family of proteins containing two EF-hand calcium-binding motifs. The dysregulated expression of the S100A11 gene has been implicated in tumour metastasis. However, the role of S100A11 protein in tumour cell response to chemotherapeutic drugs has not been characterised. METHODS: Transcript levels of S100A11 in gastric cancer were evaluated using an in-house patient cohort. Protein expression of S100A11 in gastric cancer was estimated by immunohistochemistry of a tissue microarray. The stable gastric cancer cell lines were established using lentiviral shRNA vectors. The knockdown of S100A11 was validated by qRT-PCR, PCR, and Western blot. The cellular function of S100A11 was estimated by assays of cell adhesion, migration, and invasion. The cell cytotoxic assay was performed to investigate the response to chemotherapeutic drugs. An unsupervised hierarchical clustering and principal component analysis (HCPC) was applied to unveil the dimensional role of S100A11 among all S100 family members in gastric cancer. RESULTS: High expression of S100A11 is associated with poor survival of gastric cancer patients (p < 0.001, HR = 1.85) and is an independent prognostic factor of gastric cancer. We demonstrate that S100A11 plays its role as a tumour promoter through regulating the MMP activity and the epithelial-mesenchymal transition (EMT) process. The stable knockdown of S100A11 suppresses the metastatic properties of gastric cancer cells, which include enhancing cell adhesion, but decelerating cell migration and invasion. Furthermore, the knockdown of S100A11 gene expression dramatically induces the cellular response of gastric cancer cells to the first-line chemotherapeutic drugs fluoropyrimidine 5-fluorouracil (5-FU) and cisplatin. CONCLUSION: The present study identifies S100A11 as a tumour promoter in gastric cancer. More importantly, the S100A11-specific targeting potentially presents dual therapeutic benefits by not only controlling tumour progression but also sensitising chemotherapeutic cytotoxic response.

Research on Channel Selection and Multi-Feature Fusion of EEG Signals for Mental Fatigue Detection.

With the rapid development of modern social science and technology, the pace of life is getting faster, and brain fatigue has become a sub-health state that seriously affects the normal life of people. Electroencephalogram (EEG) signals reflect changes in the central nervous system. Using EEG signals to assess mental fatigue is a research hotspot in related fields. Most existing fatigue detection methods are time-consuming or don't achieve satisfactory results due to insufficient features extracted from EEG signals. In this paper, a 2-back task is designed to induce fatigue. The weight value of each channel under a single feature is calculated by ReliefF algorithm. The classification accuracy of each channel under the corresponding features is analyzed. The classification accuracy of each single channel is combined to perform weighted summation to obtain the weight value of each channel. The first half channels sorted in descending order based on the weight value is chosen as the common channels. Multi-features in frequency and time domains are extracted from the common channel data, and the sparse representation method is used to perform feature fusion to obtain sparse fused features. Finally, the SRDA classifier is used to detect the fatigue state. Experimental results show that the proposed methods in our work effectively reduce the number of channels for computation and also improve the mental fatigue detection accuracy.

Research on the potential mechanism of Chuanxiong Rhizoma on treating Diabetic Nephropathy based on network pharmacology.

Background: Chuanxiong Rhizoma is one of the traditional Chinese medicines which have been used for years in the treatment of diabetic nephropathy (DN). However, the mechanism of Chuanxiong Rhizoma in DN has not yet been fully understood. Methods: We performed network pharmacology to construct target proteins interaction network of Chuanxiong Rhizoma. Active ingredients were acquired from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. DRUGBANK database was used to predict target proteins of Chuanxiong Rhizoma. Gene ontology (GO) biological process analyses and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were also performed for functional prediction of the target proteins. Molecular docking was applied for evaluating the drug interactions between hub targets and active ingredients. Results: Twenty-eight target genes fished by 6 active ingredients of Chuanxiong Rhizoma were obtained in the study. The top 10 significant GO analyses and 6 KEGG pathways were enriched for genomic analysis. We also acquired 1366 differentially expressed genes associated with DN from GSE30528 dataset, including five target genes: KCNH2, NCOA1, KDR, NR3C2 and ADRB2. Molecular docking analysis successfully combined KCNH2, NCOA1, KDR and ADRB2 to Myricanone with docking scores from 4.61 to 6.28. NR3C2 also displayed good docking scores with Wallichilide and Sitosterol (8.13 and 8.34, respectively), revealing good binding forces to active compounds of Chuanxiong Rhizoma. Conclusions: Chuanxiong Rhizoma might take part in the treatment of DN through pathways associated with steroid hormone, estrogen, thyroid hormone and IL-17. KCNH2, NCOA1, KDR, ADRB2 and NR3C2 were proved to be the hub targets, which were closely related to corresponding active ingredients of Chuanxiong Rhizoma.

The development and realisation of a multi-faceted system for green building planning: A case in Ningbo using the fuzzy analytical hierarchy process.

After the Green Building Regulations in the Zhejiang Province was put into effect in May 2016, cities and prefectures in the province were given directives to set their own individual targets for the provision of green buildings. The city of Ningbo decided to use this opportunity to develop a systematic procedure, using Fuzzy Analytical Hierarchy Process (FAHP), to identify which allotments within the municipal area have the greatest potential of delivering green buildings, ensuring the set targets are fair and deliverable. This paper explains in detail the use of FAHP in the production of the Specific Plans for Green Buildings for the city of Ningbo in the Zhejiang Province of China. This innovative multi-faceted method incorporates the level of development in each of the 3213 land allotments in the municipal area, assessing each one for critical aspects such as environmental potential, local economic development land-use and land prices in order to determine an individual roadmap for the ratio of green buildings to be built in each region within the city. This method incorporates a scientific process, in which Pairwise Comparison Analysis was conducted for the selected criteria and aspects to determine the weighting factors and scores in each case. This allowed planners to rank all allotments in the municipal area in terms of their potential to provide green buildings, and thus make the setting of targets to provide these accordingly. This approach breaks away from the traditional method which relies on simple estimation, which is often unjustified. Over the two years since this method was introduced, the effects had been positive, within all the allotments abiding to the set targets. Other cities and regions in China, such as the provinces of Liaoning and Hebei, have also adopted this process. The Specific Plans for Green Buildings in Ningbo also include the adoption rate of prefabricated buildings and the mandatory date for when by which new residential buildings should be fully-furnished before they are sold (this is not currently the case in most residential buildings in China). These aspects are also discussed in this paper.

Streptomyces castaneus sp. nov., a novel actinomycete isolated from the rhizosphere of Peucedanum praeruptorum Dunn.

During an investigation of microbial diversity in medicinal herbs, a novel actinomycete, strain NEAU-QHHV11T was isolated from the rhizosphere of Peucedanum praeruptorum Dunn collected from Xianglu Mountain in Heilongjiang Province, northeast China and characterized using a polyphasic approach. The organism was found to have typical characteristics of the genus Streptomyces. Phylogenetic analysis based on 16S rRNA gene sequence also indicated that strain NEAU-QHHV11T belongs to the genus Streptomyces and was most closely related to Streptomyces graminilatus NBRC 108882T (98.7 % sequence similarity) and Streptomyces turgidiscabies NBRC 16080T (98.7 % sequence similarity). The results of DNA-DNA hybridization and some phenotypic characteristics indicated that strain NEAU-QHHV11T could be distinguished from its close phylogenetic relatives. Thus, strain NEAU-QHHV11T represents a novel species of the genus Streptomyces, for which the name Streptomyces castaneus sp. nov. is proposed. The type strain is NEAU-QHHV11T (=CGMCC 4.7235T = DSM 100520T).

Nonomuraea glycinis sp. nov., a novel actinomycete isolated from the root of black soya bean [Glycine max (L.) Merr].

A novel actinomycete, designated strain NEAU-BB2C19T, was isolated from the root of black soya bean [Glycine max (L.) Merr] collected from Harbin, Heilongjiang Province, China, and characterized using a polyphasic approach. The strain was an aerobic, Gram-stain-positive actinomycete that formed extensively branched substrate mycelium and aerial hyphae. The predominant menaquinones were MK-9(H2) and MK-9(H0). The major cellular fatty acid profile consisted of iso-C16 : 0, 10-methyl C17 : 0 and 10-methyl C18 : 0. The polar lipid profile consisted of diphosphatidylglycerol, phosphatidylethanolamine, hydroxy-phosphatidylethanolamine, phosphatidylinositol, phosphatidylinositol mannoside, phosphatidylglycerol and glycolipid. The DNA G+C content was 68.2±0.4 mol%. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain NEAU-BB2C19T should be assigned to the genus Nonomuraea and formed a distinct branch with its closest neighbour Nonomuraea guangzhouensis NEAU-ZJ3T (98.75 % 16S rRNA gene sequence similarity). The morphological and chemotaxonomic properties of the strain were also consistent with those of members of the genus Nonomuraea. A combination of DNA-DNA hybridization results and some phenotypic characteristics indicated that strain NEAU-BB2C19T could be clearly differentiated from its closest phylogenetic relative. Thus, the strain is concluded to represent a novel species of the genus Nonomuraea, for which the name Nonomuraea glycinis sp. nov. is proposed. The type strain is NEAU-BB2C19T (=CGMCC 4.7430T=DSM 104838T).

Streptosporangium jiaoheense sp. nov. and Streptosporangium taraxaci sp. nov., actinobacteria isolated from soil and dandelion root (Taraxacum mongolicum Hand.-Mazz.).

Two novel actinobacteria, designated strains NEAU-Jh1-4T and NEAU-Wp2-0T, were isolated from muddy soil collected from a riverbank in Jiaohe and a dandelion root collected from Harbin, respectively. A polyphasic study was carried out to establish the taxonomic positions of these two strains. The phylogenetic analysis based on the 16S rRNA gene sequences of strains NEAU-Jh1-4T and NEAU-Wp2-0T indicated that strain NEAU-Jh1-4T clustered with Streptosporangium nanhuense NEAU-NH11T (99.32 % 16S rRNA gene sequence similarity), Streptosporangium purpuratum CY-15110T (98.30 %) and Streptosporangium yunnanense CY-11007T (97.95 %) and strain NEAU-Wp2-0T clustered with 'Streptosporangium sonchi ' NEAU-QS7 (99.39 %), 'Streptosporangium kronopolitis' NEAU-ML10 (99.26 %), 'Streptosporangium shengliense' NEAU-GH7 (98.85 %) and Streptosporangium longisporum DSM 43180T (98.69 %). Moreover, morphological and chemotaxonomic properties of the two isolates also confirmed their affiliation to the genus Streptosporangium. However, the low level of DNA-DNA hybridization and some phenotypic characteristics allowed the isolates to be differentiated from the most closely related species. Therefore, it is proposed that strains NEAU-Jh1-4T and NEAU-Wp2-0T represent two novel species of the genus Streptosporangium, for which the name Streptosporangium jiaoheense sp. nov. and Streptosporangium taraxaci sp. nov. are proposed. The type strains are NEAU-Jh1-4T (=CGMCC 4.7213T=JCM 30348T) and NEAU-Wp2-0T (=CGMCC 4.7217T=JCM 30349T), respectively.

Actinocorallia lasiicapitis sp. nov., an actinomycete isolated from the head of an ant (Lasius fuliginosus L.).

A novel actinomycete, designated strain 3H-GS17T, was isolated from the head of an ant (Lasius fuliginosus L.) and characterized using a polyphasic approach. 16S rRNA gene sequence similarity studies showed that strain 3H-GS17T belongs to the genus Actinocorallia with high sequence similarity to Actinocorallia glomerata JCM 9376T (98.13 %) and Actinocorallia longicatena JCM 9377T (97.64 %). The chemotaxonomic properties of strain 3H-GS17T were also consistent with those of members of the genus Actinocorallia. The cell wall contained meso-diaminopimelic acid and whole-cell sugars were ribose, mannose, glucose, galactose and madurose. The predominant menaquinones were MK-9(H4), MK-9(H6) and MK-9(H8). The phospholipid profile consisted of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol and phosphatidylinositol mannoside. The major fatty acids were C16 : 0 and C18 : 1ω7с. A combination of DNA-DNA hybridization experiments and phenotypic tests were carried out between strain 3H-GS17T and its closely related strains, which further clarified their relatedness and demonstrated that 3H-GS17T could be distinguished from these strains. Therefore, strain 3H-GS17T is concluded to represent a novel species of the genus Actinocorallia, for which the name Actinocorallia lasiicapitis sp. nov. is proposed. The type strain is 3H-GS17T (=DSM 100595T=CGMCC 4.7282T).

Streptomyces formicae sp. nov., a novel actinomycete isolated from the head of Camponotus japonicus Mayr.

During a screening for novel and biotechnologically useful actinobacteria in insects, a novel actinomycete with antifungal activity, designated strain 1H-GS9(T), was isolated from the head of a Camponotus japonicus Mayr ant, which were collected from Northeast Agricultural University (Harbin, Heilongjiang, China). Strain 1H-GS9(T) was characterised using a polyphasic approach. The organism was found to have morphological and chemotaxonomic characteristics typical of members of the genus Streptomyces. 16S rRNA gene sequence similarity studies showed that strain 1H-GS9(T) belongs to the genus Streptomyces with high sequence similarities to Streptomyces scopuliridis DSM 41917(T) (98.8 %) and Streptomyces mauvecolor JCM 5002(T) (98.6 %). However, phylogenetic analysis based on the 16S rRNA gene sequence indicated that it forms a monophyletic clade with Streptomyces kurssanovii JCM 4388(T) (98.6 %), Streptomyces xantholiticus JCM 4282(T) (98.6 %) and Streptomyces peucetius JCM 9920(T) (98.5 %). Thus, a combination of DNA-DNA hybridization experiments and phenotypic tests were carried out between strain 1H-GS9(T) and the above-mentioned five strains, which further clarified their relatedness and demonstrated that strain 1H-GS9(T) could be distinguished from these strains. Therefore, the strain is concluded to represent a novel species of the genus Streptomyces, for which the name Streptomyces formicae sp. nov. is proposed. The type strain is 1H-GS9(T) (=CGMCC 4.7277(T) = DSM 100524(T)).

Human NCF190H Variant Promotes IL-23/IL-17-Dependent Mannan-Induced Psoriasis and Psoriatic Arthritis.

Recently, a major single nucleotide variant on the NCF1 gene, leading to an amino acid replacement from arginine to histidine at position 90 (NCF1R90H), associated with low production of reactive oxygen species (ROS), was found to be causative for several autoimmune diseases. Psoriasis in the skin (PsO) and psoriatic arthritis (PsA) were induced with mannan by intraperitoneal injection or epicutaneous application, evaluated by visual and histology scoring. Immunostaining was used to identify macrophages, NCF1, and keratinocytes. The population of immune cells was quantified by flow cytometry, gene expression was analyzed by RT-qPCR, and the JAK/STAT signaling pathway was investigated by immunohistochemical staining and western blot. We found that the low ROS responder NCF190H variant promotes PsO and PsA (the MIP model). The NCF190H-expressing mice had hyperactivated macrophages, expanded keratinocytes, and dramatically increased numbers of γδT17 cells with upregulated IL-17A, IL-23, and TNF-α. In addition, the JAK1/STAT3 signaling pathway was also upregulated in cells in the psoriatic skin tissues of Ncf190H mice. To summarize, a defined SNP (NCF1-339, also named NCF190H) was found to activate the IL-23/IL-17 axis and JAK-STAT signaling pathways, leading to hyperactivation of macrophages and keratinocytes and causing mouse psoriasis and psoriatic arthritis.

An improved multi-source domain adaptation network for inter-subject mental fatigue detection based on DANN.

OBJECTIVES: Electroencephalogram (EEG) is often used to detect mental fatigue because of its real-time characteristic and objective nature. However, because of the individual variability of EEG among different individuals, tedious and time-consuming calibration sessions are needed. METHODS: Therefore, we propose a multi-source domain adaptation network for inter-subject mental fatigue detection named FLDANN, which is short for focal loss based domain-adversarial training of neural network. As for mental state feature extraction, power spectrum density is extracted based on the Welch method from four sub-bands of EEG signals. The features of the source domain and target domain are fed into the FLDANN network. The contributions of FLDANN include: (1) It uses the idea of adversarial to reduce feature differences between the source and target domain. (2) A loss function named focal loss is used to assign weights to source and target domain samples. RESULTS: The experiment result shows that when the number of the source domains increases, the classification accuracy of domain-adversarial training of neural network (DANN) gradually decreases and finally tends to be stable. The proposed method achieves an accuracy of 84.10% ± 8.75% on the SEED-VIG dataset and 65.42% ± 7.47% on the self-designed dataset. In addition, the proposed method is compared with other domain adaptation methods and the results show that the proposed method outperforms those state-of-the-art methods. CONCLUSIONS: The result proves that the proposed method is able to solve the problem of individual differences across subjects and to solve the problem of low classification performance of multi-source domain transfer learning.

Kaempferol modulates IFN-γ induced JAK-STAT signaling pathway and ameliorates imiquimod-induced psoriasis-like skin lesions.

Immune-mediated inflammation contributes to the development of psoriasis. However, long-term treatment with global immunosuppressive agents may cause a variety of side effects including recurrent infections. Kaempferol (KP), a natural flavonol, present in various plants is proposed to be useful for the treatment of psoriasis patients. Nevertheless, an explicit understanding of KP induced mechanisms is a prerequisite for its use in clinics. Therefore, we investigated the therapeutic effects and potential mode of action of KP using IFN-γ induced HaCaT cells and imiquimod-induced psoriasis-like skin lesions in mice. In this study, we found KP reduced intracellular ROS production, inhibited rhIFN-γ-induced IFN-γR1 expression, and up-regulated SOCS1 levels in HaCaT cells. In addition, KP inhibited rhIFN-γ-induced phosphorylation of JAK-STAT signaling molecules in HaCaT cells. Most importantly, KP alleviated imiquimod-induced psoriasis-like skin lesions in mice, histopathology and proportion of DCs in the skin. Besides, it reduced the population of γδT17 cells in the lymph nodes of the psoriatic mice and also decreased the gene expression of many proinflammatory cytokines, including interleukin IL-23, IL-17A, TNF-α, IL-6, and IL-1ß in addition to down-regulation of the proinflammatory JAK-STAT signaling pathway. Thus, KP modulated IFN-γ induced JAK-STAT signaling pathway by inducing IFN-γR1 expression and up-regulating SOCS1 expression. In addition, KP also ameliorated imiquimod-induced psoriasis by reducing the dendritic cell numbers, and γδT17 cell population, along with down- modulation of the JAK-STAT pathway.

Nanostructure formation and passivation of large-area black silicon for solar cell applications.

Nanoscale textured silicon and its passivation are explored by simple low-cost metal-assisted chemical etching and thermal oxidation, and large-area black silicon was fabricated both on single-crystalline Si and multicrystalline Si for solar cell applications. When the Si surface was etched by HF/AgNO(3) solution for 4 or 5 min, nanopores formed in the Si surface, 50-100 nm in diameter and 200-300 nm deep. The nanoscale textured silicon surface turns into an effective medium with a gradually varying refractive index, which leads to the low reflectivity and black appearance of the samples. Mean reflectance was reduced to as low as 2% for crystalline Si and 4% for multicrystalline Si from 300 to 1000 nm, with no antireflective (AR) coating. A black-etched multicrystalline-Si of 156 mm × 156 mm was used to fabricate a primary solar cell with no surface passivation or AR coating. Its conversion efficiency (η) was 11.5%. The cell conversion efficiency was increased greatly by using surface passivation process, which proved very useful in suppressing excess carrier recombination on the nanostructured surface. Finally, a black m-Si cell with efficiency of 15.8% was achieved by using SiO(2) and SiN(X) bilayer passivation structure, indicating that passivation plays a key role in large-scale manufacture of black silicon solar cells.

Application of Virtual Reality Based on 3D-CTA in Intracranial Aneurysm Surgery.

As a popular technology in the field of human-computer interaction, virtual reality (VR) brings a brand new sensory experience to users by generating the environment. In recent years, while introducing the application of virtual reality technology, researchers have done a lot of work around virtual reality in many fields, such as the application of virtual reality technology in medical procedures. Combining the immersive and expandable features of virtual reality can improve the safety and accuracy of surgery. This article mainly introduces the application of 3D-CTA virtual reality technology in intracranial aneurysm surgery and aims to provide some ideas and directions for the improvement and progress of intracranial aneurysm surgery. This paper presents a research method based on virtual reality technology 3D-CTA in intracranial aneurysm surgery, including the application overview of 3D-CTA in intracranial aneurysm surgery and the virtual reality algorithm based on 3D-CTA for intracranial arteries. In addition, there is also the application of virtual reality CTA technology in the design of the intracranial aneurysm application system. Experimental results show that the average accuracy of 3D-CTA diagnosis based on virtual reality is 90.81%, and it can be put into use in the next step.

Application of electrochemical methods for the detection of abiotic stress biomarkers in plants.

Abiotic stress is the main cause of low productivity in plants. Therefore, it is important to detect stress and respond to it in a timely manner to avoid irreversible damage to plant productivity and health. The application of traditional methods in agriculture is limited by expensive equipment and cumbersome sample processing. More effective detection methods are urgently needed due to the trace amounts and low stabilities of plant biomarkers. Electrochemical detection methods have the unique advantages of high accuracy, a low detection limit, fast response and easy integration with systems. In this review, the application of three types of electrochemical methods to phytohormone assessment is highlighted including direct electrochemical, immunoelectrochemical, and photoelectrochemical methods. Research on electrochemical methods for detecting abiotic stress biomarkers, including various phytohormones, is also summarized with examples. To date, the detection limit of exogenous plant hormones can reach pg/mL or even lower. Nevertheless, more efforts need to be made to develop a portable instrument for in situ online detection if electrochemical sensors are to be applied to the detection of the endogenous hormones or the physiological state of plants. Additionally, plant-wearable sensors that can be directly attached to or implanted into plants for continuous, noninvasive and real-time monitoring are emphasized. Finally, rational summaries of the considered methods and present challenges and future prospects in the field of abiotic stress detection-based electrochemical biosensors are thoroughly discussed.

Lead DEAD/H box helicase biomarkers with the therapeutic potential identified by integrated bioinformatic approaches in lung cancer.

DEAD/H box helicases are implicated in lung cancer but have not been systematically investigated for their clinical significance and function. In this study, we aimed to evaluate the potential of DEAD/H box helicases as prognostic biomarkers and therapeutic targets in lung cancer by integrated bioinformatic analysis of multivariate large-scale databases. Survival and differential expression analysis of these helicases enabled us to identify four biomarkers with the most significant alterations. These were found to be the negative prognostic factors DDX11, DDX55 and DDX56, and positive prognostic factor DDX5. Pathway enrichment analysis indicates that MYC signalling is negatively associated with expression levels of the DDX5 gene while positively associated with that of DDX11, DDX55 and DDX56. High expression levels of the DDX5 gene is associated with low mutation levels of TP53 and MUC16, the two most frequently mutated genes in lung cancer. In contrast, high expression levels of DDX11, DDX55 and DDX56 genes are associated with high levels of TP53 and MUC16 mutation. The tumour-infiltrated CD8 + T and B cells positively correlate with levels of DDX5 gene expression, while negatively correlate with that of the other three DEAD box helicases, respectively. Moreover, the DDX5-associated miRNA profile is distinguished from the miRNA profiles of DDX11, DDX55 and DDX56, although each DDX has a different miRNA signature. The identification of these four DDX helicases as biomarkers will be valuable for prognostic prediction and targeted therapeutic development in lung cancer.