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Fish culture plays an important role in supplying high-quality proteins and omega-3 (n-3) long-chain polyunsaturated fatty acids. Aquaculture has been the fastest growing sector in agriculture. Fishmeal is an important component of commercial fish feeds, but ensuring a sustainable supply of fishmeal is in question. A good source of proteins in aquafeeds is insects. For the past 20 years, investigations have been carried out on insect meals as alternative sources for fishmeal. Thus far, the results on replacing fishmeal in feeding aquaculture species have been promising. However, some challenging issues including costs and scaling up of insect production remains. In this review, we aim to summarize the status of applying meals of eight insect species in formulated aquafeeds. We also discussed issues in replacing fishmeal in fish feeds with insect meals and listed some future research directions to make insect meals an important source of proteins for green, profitable and sustainable (GPS) aquaculture. It is certain that in the near future, large-scale insect farming and processing to produce insect meals as an ingredient of fish feeds will have positive impact on the sustainability and profitability of aquaculture.

Iridoviruses are DNA virus and have caused huge economic losses in the aquaculture industry. The aim of this study was to establish a colorimetric loop-mediated isothermal amplification (LAMP) protocol for the on-site detection of Singapore grouper iridovirus (SGIV). The SGIV-VP61 gene was chosen as the target gene to develop a colorimetric LAMP assay. The optimized condition of the colorimetric LAMP assay was incubation at 63 °C for 1 h. Samples infected with SGIV could be detected with the color change from yellow into pink. The sensitivity of the developed assay is 5.66 copies/μL of the viral DNA template. This sensitivity was about 1000 times higher than that of conventional PCR while it was slightly lower than the one-step semi-nested PCR assay. A total of 60 DNA samples extracted from the fin tissue of the SGIV-infected Asian seabass were examined for SGIV by colorimetric LAMP, semi-nested PCR and conventional PCR. The results of the colorimetric LAMP assay showed 94.87 % agreement with the semi-nested PCR. In addition, the DNA extraction method using NaOH showed a better performance in the colorimetric LAMP assay. Taken together, the colorimetric LAMP established was a sensitive, rapid and specific method for the detection of SGIV. SGIV was not detected in samples randomly taken from a genetically improved line of the Asian seabass. However, some seabass obtained from the local markets were found to contain SGIV. Thus, the LAMP assay has the potential application in the diagnosis of iridovirus diseases in the aquaculture industry.

Attached bacteria of Microcystis play important roles in the occurence, outbreak and decline of Microcystis water blooms. In this study, a novel actinobacterium, designated strain JXJ CY 38 T, was isolated from the culture mass of Microcystis aeruginosa FACHB-905 (MAF), collected from Lake Dianchi, south-west, China. The strain was found to be a Gram-stain positive, short rod, catalase positive and oxidase negative. The isolate was found to be able to grow at 5.0-38.0 °C (optimum, 28.0 °C), pH 4.0-11.0 (optimum, 7.0-8.0) and 0-3.0% (w/v, optimum, 0%) NaCl. Based on 16S rRNA gene sequences, strain JXJ CY 38 T shows high similarities to Nocardioides furvisabuli JCM 13813 T (99.0%) and Nocardioides alpinus JCM 18960 T (98.7%), and less than 98.2% similarities to other members of the genus. The major cellular fatty acids (> 10.0%) were identified as iso-C16:0 (23.6%), C18:1ω9c (18.2%) and C17:1ω8c (16.4%), while the predominant menaquinone was found to be MK-8 (H4). The diagnostic diamino acids in the cell wall peptidoglycan were identified as aspartic acid, glutamic acid, glycine and alanine, with mannose, ribose and arabinose as whole cell sugars. The polar lipids were found to be diphosphatidylglycerol, phosphatidylglycerol, a phospholipid, phosphatidylcholine and an unidentified lipid. The DNA G + C content was determined to be 71.3%. The digital DNA-DNA hybridization and average nucleotide identity values between strain JXJ CY 38 T and the type strains N. furvisabuli JCM 13813 T and N. alpinus JCM 18960 T were 49.4% and 37.7%, and 92.0% and 83.4%, respectively. On the basis of the above taxonomic data and differences in physiological characteristics from the closely related type strains, strain JXJ CY 38 T was determined to represent a novel species of genus Nocardioides, for which the name Nocardioides lacusdianchii sp. nov. is proposed. The type strain is JXJ CY 38 T (= KCTC 49381 T = CGMCC 4.7665 T). Strain JXJ CY 38 T apparently exhibits complex effects on the interactions between MAF and other attached bacteria, including the promotion or inhibition of the growth of MAF and bacteria, and the synthesis and release of microcystins by MAF.

Chia (Salvia hispanica L.), originated in central and southern Mexico and Guatemala, is an emerging industry crop due to its high content of omega‐3 fatty acids and dietary fiber in its seeds. The seeds also have a high concentration of proteins and essential amino acids, and are becoming a promising source of bioactive peptides. Polymorphic DNA markers are essential tools to analyse genetic diversity and to accelerate genetic improvement. However, in chia, polymorphic and codominant DNA markers are still lacking. In this study, fourteen polymorphic microsatellites were identified from DNA sequences and were characterized. The average allele number was 4.8 while the expected and observed heterozygosity was 0.24 and 0.34, respectively. The average probability of identity (PI) was 0.50 while the combined PI was 9 × 10–6. These first 14 microsatellites in chia are useful in genetic analysis and traceability. These 14 polymorphic microsatellites were used in analysing genetic diversity and population relationships in six cultivars originating in Mexico, Australia and Bolivia. Results showed that allelic diversity and gene diversity were low and ranged from 2.79 to 3.64 and 0.27 to 0.38, respectively. The Mexico black cultivar showed the highest allelic (3.64) and gene diversity (0.38). The six cultivars were closely related with high identity (≥ 0.893). Taken together, these chia cultivars contain low genetic variation. Therefore, to initiate a breeding program for improving traits, it is essential to use seeds from multiple cultivars to enlarge genetic variation in the founder population.

BACKGROUND Garlic (Allium sativum L.), whose bioactive components are mainly organosulfur compounds (OSCs), is a herbaceous perennial widely consumed as a green vegetable and a condiment. Yet, the metabolic enzymes involved in the biosynthesis of OSCs are not identified in garlic. RESULTS Here, a full-length transcriptome of purple garlic was generated via PacBio and Illumina sequencing, to characterize the garlic transcriptome and identify key proteins mediating the biosynthesis of OSCs. Overall, 22.56 Gb of clean data were generated, resulting in 454 698 circular consensus sequence (CCS) reads, of which 83.4% (379 206) were identified as being full-length non-chimeric reads - their further transcript clustering facilitated identification of 36 571 high-quality consensus reads. Once corrected, their genome-wide mapping revealed that 6140 reads were novel isoforms of known genes, and 2186 reads were novel isoforms from novel genes. We detected 1677 alternative splicing events, finding 2902 genes possessing either two or more poly(A) sites. Given the importance of serine O-acetyltransferase (SERAT) in cysteine biosynthesis, we investigated the five SERAT homologs in garlic. Phylogenetic analysis revealed a three-tier classification of SERAT proteins, each featuring a serine acetyltransferase domain (N-terminal) and one or two hexapeptide transferase motifs. Template-based modeling showed that garlic SERATs shared a common homo-trimeric structure with homologs from bacteria and other plants. The residues responsible for substrate recognition and catalysis were highly conserved, implying a similar reaction mechanism. In profiling the five SERAT genes' transcript levels, their expression pattern varied significantly among different tissues. CONCLUSION This study's findings deepen our knowledge of SERAT proteins, and provide timely genetic resources that could advance future exploration into garlic's genetic improvement and breeding. © 2021 Society of Chemical Industry.

Common carp is a fish species of economic importance in China;traditionally it is mostly salt-fermented. In the fermenting process, the bacterial community of spontaneously fermented fish is important for its flavour and quality. However, very few studies have been conducted about the relationship between bacterial community and development of flavour involved in the salt-fermentation of carp. Therefore, we explored this relationship by determining the flavour components, including amino acids, and changes in volatile flavour and bacterial metabolite. Samples were taken during fermentation on the days 0, 10, 20, 30, 40 and 50. The second-generation 16S recombinant DNA (rDNA) sequencing was performed to analyze the composition of bacteria. Contents of amino acids were determined by reverse-phase high-performance liquid chromatography combined with ultraviolet detection. The volatile components were analyzed with solid-phase microextraction–gas chromatography-mass spectrometry. Enterococcus, Lactobacillus, Lactococcus, Leuconostoc, and Staphylococcus were the dominant bacteria. The bidirectional orthogonal partial least squares approach was used to analyze the correlation between bacterial succession and flavour component dynamics. This study would help to better understand the role of bacteria in the fermented fish meat flavour and support the industrial production of fermented fish.

Background Hepatocyte growth factor (HGF) binds to the c-mesenchymal-epithelial transition (C-MET) receptor and activates downstream signaling pathways, playing an essential role in the development of various cancers. Given the role of this signaling pathway, the primary therapeutic direction focuses on identifying and designing HGF inhibitors, antagonists and other molecules to block the binding of HGF to C-MET, thereby limiting the abnormal state of other downstream genes. Methods This study focuses on the analysis of immune-related genes and corresponding immune functions that are significantly associated with the HGF/c-MET pathway using transcriptome data from 11 solid tumors. Results We systematically analyzed 11 different cancers, including expression correlation, immune infiltration, tumor diagnosis and survival prognosis from HGF/c-MET pathway and immune regulation, two biological mechanisms having received extensive attention in cancer analysis. Conclusion We found that the HGF/c-MET pathway affected the tumor microenvironment mainly by interfering with expression levels of other genes. Immune infiltration is another critical factor involved in changes to the tumor microenvironment. The downstream immune-related genes activated by the HGF/c-MET pathway regulate immune-related pathways, which in turn affect the degree of infiltration of immune cells. Immune infiltration is significantly associated with cancer development and prognosis.

The metastasis of tumor cells is a challenge for the clinical treatment of glioma. Epithelial-mesenchymal transition (EMT) contributes to glioma cell invasiveness. Our previous study confirmed that the expression of miRNA-451, which inhibits the PI3K/Akt signaling pathway by directly targeting CAB39 and plays a repressive role in glioma, is downregulated in glioma. However, the specific mechanism of miRNA-451 regulation in glioma is unclear. In this study, we investigated whether miRNA-451 blocks the processes of EMT and metastasis in glioma cells in vivo and in vitro. By targeting CAB39, miRNA-451 likely triggers the PI3K/Akt/Snail signaling pathway to reduce glioma proliferation, invasion, migration and EMT. We used Western blotting experiments to demonstrate that overexpression of miRNA-451 significantly reduced p-AKT(Ser473), N-cadherin, Vimentin, Twist, Snail and Cyclin D1 expression and increased E-cadherin expression. We demonstrated that overexpression of miR-451 suppressed glioma cell proliferation, invasion, migration and EMT by MTT and colony formation assays, Transwell assays, wound healing assays and animal experiments. Taken together, these results suggest that miRNA-451 can reduce EMT and metastasis in glioma cells through the suppression of the PI3K/Akt/Snail signaling pathway by targeting CAB39 in vitro and in vivo. miR-451 may be a new target for glioma treatment.

In May 2020, a new taxon of Euphorbia, Euphorbiaceae was collected from a dry hillside of Dongsheng District, Ordos City, Inner Mongolia. The morphological characteristics of the specimens analyzed differ from those of the known Euphorbia species from this region; therefore, we suspected this may be a new species, and we set to analyze the ITS2 sequences of some Euphorbia species. The results show that the new taxon belongs to the sect. Esula of Euphorbia subg. Esula. It is similar to Euphorbia esula (description from Flora of China) but does not belong to the same species. Concomitantly, plant morphological data and pollen morphology results show significant differences between the new taxon, E. esula and E. caesia, a finding that supports the delimitation of this new taxon, which is named Euphorbia mongoliensis in accordance with its geographical distribution.

Background Osteoporosis is damaging the health of women worldwide. Osteoporosis results from the imbalance between bone resorption and formation, which may be regulated by homeobox A2 (Hoxa2). However, the specific role and mechanism of Hoxa2 in osteogenesis and dexamethasone (Dex)-induced osteoporosis remain unknown. Objectives The present study investigated the effect of Hoxa2 on differentiation and osteoblastogenesis. Material and methods Alkaline phosphatase staining and immunofluorescence staining were performed to evaluate the differentiation of MC3T3-E1 cells. Runt-related transcription factor 2 (Runx2), osteoprotegerin (OPG) and receptor activator of nuclear factor-kappa B ligand (RANKL) in Dex stimulated osteoblastic MC3T3-E1 cells, and Dex-induced osteoporotic rats were estimated using western blot and quantitative polymerase chain reaction (qPCR). Serum markers of bone turnover were determined using enzyme-linked immunosorbent assay (ELISA). Trabecular bones of femur tissues were observed using hematoxylin and eosin (H&E) staining. Results Hoxa2 short hairpin RNA significantly promoted the differentiation of MC3T3-E1 cells and expression of Runx2 and OPG in Dex-treated MC3T3-E1 cells and osteoporotic rats but inhibited the expression of RANKL. Furthermore, silencing Hoxa2 resulted in the upregulation of bone alkaline phosphatase but suppressed the expression of tartrate-resistant acid phosphatase and C-terminal cross-linked telopeptides of type I collagen. Conclusions Silencing Hoxa2 reversed the Dex-induced inhibition of osteoblastogenesis by modulating Runx2 and RANK-RANKL-OPG axis.

Parkinson's disease (PD) is a severe neurodegenerative disorder caused by the progressive loss of dopaminergic neurons in the substantia nigra and affects millions of people. Currently, mitochondrial dysfunction is considered as a central role in the pathogenesis of both sporadic and familial forms of PD. Mitophagy, a process that selectively targets damaged or redundant mitochondria to the lysosome for elimination via the autophagy devices, is crucial in preserving mitochondrial health. So far, aberrant mitophagy has been observed in the postmortem of PD patients and genetic or toxin-induced models of PD. Except for mitochondrial dysfunction, mitophagy is involved in regulating several other PD-related pathological mechanisms as well, e.g., oxidative stress and calcium imbalance. So far, the mitophagy mechanisms induced by PD-related proteins, PINK1 and Parkin, have been studied widely, and several other PD-associated genes, e.g., DJ-1, LRRK2, and alpha-synuclein, have been discovered to participate in the regulation of mitophagy as well, which further strengthens the link between mitophagy and PD. Thus, in this view, we reviewed mitophagy pathways in belief and discussed the interactions between mitophagy and several PD's pathological mechanisms and how PD-related genes modulate the mitophagy process.

Prunus triloba var. plena, also known as flowering plum, is a perennial deciduous shrub admired for its brilliant pink-purple blooms. Chloroplast (cp) DNA is highly conserved in structure and gene arrangement, making cp genomic data valuable resources for species delimitation and phylogenetics. The cp genome of P. triloba var. plena was de novo assembled with the aim of developing cp-derived molecular markers and deepening the understanding of phylogenetic relationship among Prunus species. The complete cp genome was 158,022 bp in length, with a GC content of 36.8%. The plastome featured a typical quadripartite structure, consisting of a pair of inverted repeat (IR) regions of 26,379 bp, separated by a large single copy (LSC) region of 86,242 bp, and a small single copy (SSC) region of 19,022 bp. The cp genome encoded 134 genes, including 87 protein-coding genes, 39 tRNA genes, and 8 rRNA genes. A total of 59 simple sequence repeat (SSR) were identified, 68% of which were located in the intergenic regions. An obvious A/T bias was observed in the majority of SSRs detected. Besides, 48 repeats in different sizes and types were detected. These repeats, together with SSRs and the divergence hotspots detected, could serve as markers facilitating species discrimination and evolutionary research in Prunus. Using plastome sequences, we re-investigated the phylogenetic relationship among 32 Prunus species. These species explicitly clustered into three monophyletic clades, among which P. triloba var. plena was closely related to species in the subgenera Amygdalus and Prunus.

Ribes odoratum, commonly known as clove currant, is a perennial deciduous shrub noted for its long-lasting fragrant flowers and edible fruits. Owing to its ornamental values, this species has been widely used in city gardening and urban landscaping. Here, the complete cp genome of R. odoratum was de novo assembled for the first time. The plastome is 157,152 bp in length, with a GC content of 38.2%. The cp genome featured a typical quadripartite structure, consisting of a pair of inverted repeat regions of 25,961 bp, separated by a large single copy region of 86,896 bp, and a small single copy region of 18,333 bp. A total of 131 genes were annotated in the plastome, including 86 protein coding genes, 37 tRNA genes, and 8 rRNA genes. 56 SSRs were identified, among which, 82.35% were located in the intergenic regions. A strong A/T bias in base composition was observed in these cpSSRs. In addition, 49 repeats of different sizes and types were also found in the plastome. Through comparison, seven divergence hotspots were identified between the cp genomes of R. odoratum and R. fasciculatum var. chinense. Sequences of these divergent regions could be developed as potential markers for species delimitation in further studies. We re-investigated the relationship aomong 32 Saxifragales species through plastome-based phylogenywhich revealed that R. odoratum as a sister of R. fasciculatum var. chinense. Thus, our study provides genomic resources and valuable reference for marker development and phylogenomics in Ribes.

Traditional therapeutic strategies for spinal cord injury (SCI) are insufficient to repair locomotor function because of the failure of axonal reconnection and neuronal regeneration in the injured central nervous system (CNS). Neural stem cell (NSC) transplantation has been considered a potential strategy and is generally feasible for repairing the neural circuit after SCI; however, the most formidable problem is that the neuronal differentiation rate of NSCs is quite limited. Therefore, it is essential to induce the neuronal differentiation of NSCs and improve the differentiation rate of NSCs in spinal cord repair. Our results demonstrate that both Wnt5a and miRNA200b-3p could promote NSC differentiation into neurons and that Wnt5a upregulated miRNA200b-3p expression through MAPK/JNK signaling to promote NSC differentiation into neurons. Wnt5a could reduce RhoA expression by upregulating miRNA200b-3p expression to inhibit activation of the RhoA/Rock signaling pathway, which has been reported to suppress neuronal differentiation. Overexpression of RhoA abolished the neurogenic capacity of Wnt5a and miRNA200b-3p. In vivo, miRNA200b-3p was critical for Wnt5a-induced NSC differentiation into neurons to promote motor functional and histological recovery after SCI by suppressing RhoA/Rock signaling. These findings provide more insight into SCI and help with the identification of novel treatment strategies., Spinal cord injury: Boost for neural stem cell therapies Incorporating key molecules into neural stem cells enhances their ability to differentiate correctly and promote repair following spinal cord injury. Spinal cord injuries can have a debilitating effect on patients’ lives, yet there are no therapies that fully restore movement and sensation. Therapies based on neural stem cells (NSCs) show promise, but initial studies show many NSCs differentiate into astrocytes, supportive cells that do not conduct nerve impulses, instead of neurons, leading to treatment failure. Yong Wan and Le Wang at Sun Yat-sen University in Guangzhou, China, and co-workers demonstrated that adding a protein called Wnt5a and a specific microRNA molecule to NSCs significantly increases differentiation into neurons. Wnt5a suppresses a signalling pathway that otherwise interferes with NSC differentiation. Experiments on rat models showed that the therapy improved locomotor function and tissue repair after injury.

Sorbaria kirilowii is a deciduous perennial admired for its showy white blossoms. Though of importance for horticultural purposes, the plastomic study concerning this species is still lacking. Here, the plastome of S. kirilowii was de novo assembled using the high-throughput sequencing data. The complete plastome assembly of S. kirilowii was 160,810 bp in length, with a GC content of 36.03%. It featured a typical quadripartite structure, containing a pair of inverted repeats (IRs; 26,338 bp) separated by a large single-copy (LSC; 88,762 bp) and a small single-copy (SSC, 19,372 bp). In total, 132 genes were annotated in the plastome, including 87 protein-coding genes, 8 rRNA genes, and 37 tRNA genes. Furthermore, 63 SSRs, most of which were AT-rich, were identified in the cp genome of S. kirilowii. 71.7% of the cpSSRs were shown to be located in the intergenic regions. In addition, 49 repeats of varying sizes and types were also identified in the plastome. Through comparison, eight divergence hotspots were identified between the plastome of S. kirilowii and S. sorbifolia var. stellipila. These variable regions could potentially be developed into molecular markers for species delimitation or phylogenetics in future studies. We re-investigated the relationship among 17 Rosaceae species using the plastomic sequences, and S. kirilowii was shown to be a sister to S. sorbifolia var. stellipila. Overall, this study provides plastomic resources which could facilitate marker development and phylogenomics of Rosaceae.

Multidrug-resistant (MDR) bacteria-induced infections are becoming challenging issues threatening human health and life. Current antibiotics can hardly tackle this problem. Herein, we present a strategy to prepare mercaptophenylboronic acid (MBA)-activated gold nanoparticles (Au NPs) as an antibacterial agent against MDR bacteria. Both Au NPs and MBA cannot serve as antibiotics. However, when MBA attaches on Au NPs, the Au_MBA NPs show potent antibacterial activities against Gram-positive MDR clinical isolates (e.g., MDR Staphyloccocus aureus, MDR S. aureus; MDR Staphyloccocus epidermidis, MDR S. epidermidis). Furthermore, Au_MBA NPs show an extremely high median lethal dose (LD50,i.v., 960 mg/kg), which is much higher than those of most of the clinically used antibiotics. As an application example, we dope Au_MBA NPs with electrospun poly(e-caprolactone) (PCL)/gelatin nanofibrous membranes as wound dressings, which show striking ability to remedy S. aureus- or MDR S. aureus-infected full-thickness skin wounds on rats. Our study provides a novel strategy for treating MDR bacteria-infected wounds in a simple, low-cost, and efficient way, which holds promise for broad clinical applications.

IRAK-4 is a serine/threonine kinase that can bind to interleukin-1 receptor induced by interleukin-1. It plays a key role in the Toll-like receptor signaling pathway and is involved in innate and adaptive immune responses. In this study, piscine IRAK-4 significantly activated nuclear factor (NF)-κB signaling in grouper spleen cells. Grouper (Epinephelus coioides) IRAK-4 (EcIRAK-4) co-localized with EcMyD88 and did not impair EcMyD88-dependent NF-κB activation. Different doses of EcIRAK-4 caused different degrees of nuclear translocation of the transcription factor NF-κB p65 subunit, and it induced transcription of multiple pro-inflammatory cytokines. Using expression vectors of deletion domains or mutations at important sites of EcIRAK-4, we found that the EcIRAK-4 kinase domain is necessary for its signal transduction function. The conserved amino acid sites performed functions similar to those in mammals, and grouper-specific amino acids such as E339 also played important roles. These findings provide information about the functional characteristics of IRAK-4 in lower vertebrates.

Isolation and screening of microalgal species from natural habitats should be a continues work to discover effective species for biofuel generation and wastewater treatment. In the current study, microalgal species namely Tetradesmus dimorphus GEEL-04 and Desmodesmus asymmetricus GEEL-05 were isolated, identified, and assessed for growth kinetics, nutrients removal efficiency, and whole biomass composition. T. dimorphus showed higher growth (1.46 OD680nm) compared with D. asymmetricus (1.16 OD680nm), and both showed 99% total nitrogen and total phosphorous removal. T. dimorphus and D. asymmetricus accumulated higher protein content (40.02 and 45.10%), carbohydrate (31.91 and 24.64%), and lipid (15.41 and 24.16%), respectively. The FTIR spectra absorbance revealed different function groups in microalgal biomass available for biofuel generation. Elemental analysis of microalgal biomass showed high carbon content 50.13% and 43.01% for T. dimorphus and D. asymmetricus, respectively. Thermogravimetric analysis indicated ≥ 80% volatile content in both isolates. The fatty acid composition of both microalgal strains showed high palmitic acid and linoleic acid corresponding to high quality biodiesel. These results indicated that the T. dimorphus and D. asymmetricus could be potential candidates for high biocomponents accumulation and N, P removal.

Schizophrenia (SCZ) is a neuropsychiatric disorder with aberrant expression of multiple genes. However, identifying its exact causal genes remains a considerable challenge. The brain-specific transcription factor POU3F2 (POU domain, class 3, transcription factor 2) has been recognized as a risk factor for SCZ, but our understanding of its target genes and pathogenic mechanisms are still limited. Here we report that POU3F2 regulates 42 SCZ-related genes in knockdown and RNA-sequencing experiments of human neural progenitor cells (NPCs). Among those SCZ-related genes, TRIM8 (Tripartite motif containing 8) is located in SCZ-associated genetic locus and is aberrantly expressed in patients with SCZ. Luciferase reporter and electrophoretic mobility shift assays (EMSA) showed that POU3F2 induces TRIM8 expression by binding to the SCZ-associated SNP (single nucleotide polymorphism) rs5011218, which affects POU3F2-binding efficiency at the promoter region of TRIM8. We investigated the cellular functions of POU3F2 and TRIM8 as they co-regulate several pathways related to neural development and synaptic function. Knocking down either POU3F2 or TRIM8 promoted the proliferation of NPCs, inhibited their neuronal differentiation, and impaired the excitatory synaptic transmission of NPC-derived neurons. These results indicate that POU3F2 regulates TRIM8 expression through the SCZ-associated SNP rs5011218, and both genes may be involved in the etiology of SCZ by regulating neural development and synaptic function.

Objectives Understanding the nature of Mycobacterium leprae transmission is vital to implement better control strategies for leprosy elimination. The present study expands the knowledge of county-level strain diversity, distribution, and transmission patterns of leprosy in endemic provinces of China. Methods We genetically characterized 290 clinical isolates of M. leprae from four endemic provinces using variable number tandem repeats (VNTR) and single nucleotide polymorphisms (SNPs). Attained genetic profiles and cluster consequences were contrasted with geographical and migration features of leprosy at county levels. Results Considering the allelic variability of 17 VNTR loci by the discriminatory index, (GTA)9, (AT)17, (AT)15, (TA)18, (TTC)21, and (TA)10 are reported to be more highly polymorphic than other loci. The VNTR profile generated the low-density clustering pattern in the counties of Sichuan and Yunnan, whereas clusters have been observed from the isolates from Huayuan (N = 6), Yongding (N = 3), Zixing (N = 3), Chenxi (N = 2) and Zhongfang (N = 2) counties of Hunan, and Zhijin (N = 3), Anlong (N = 2), Zhenning (N = 2), and Xixiu (N = 2) counties of Guizhou. In some clusters, people’s social relations have been observed between villages. From the 290 clinical isolates, the most predominantly reported SNP was 3K (278, 95.8%), followed by SNP 1D (10, 3.4%), which are typically observed to be predominant in China. We also detected the novel SNP 3J (2, 0.8%), which has not yet been reported in China. Conclusion The clustering pattern of M. leprae indicates the transmission of leprosy still persists at county levels, suggesting that there is a need to implement better approaches for tracing the close contacts of leprosy patients.

Potato late blight caused by Phytophthora infestans is one of the most serious plant diseases worldwide. Cyclic lipopeptides (CLPs) extracted from Bacillus strains exhibit a promising effect in the biocontrol of a variety of phytopathogens. However, the specific inhibitory effects and underlying mechanisms of CLPs against P. infestans are poorly understood. In this study, we showed that Bacillus pumilus W-7 can inhibit the growth of P. infestans mycelium. Two metabolites from W-7, surfactin and fengycin B, were identified using MS/MS. Fengycin B inhibited mycelium growth by inducing mycelium deformations, oxidative damage, and mitochondrial dysfunction. Surfactin induced potato plant defense responses by increasing the expression of the biocontrol genes (pod, pal, and cat) and their enzyme activities (POD, PAL, and CAT). Also, surfactin and fengycin B could exhibit a synergistic inhibitory effect on P. infestans. Taken together, our findings indicate that B. pumilus W-7 and its CLPs are potential environmentally friendly and effective biocontrol agents for the preservation of potato crops. KEY POINTS: • Lipopeptides of surfactin and fengycin B are extracted from Bacillus pumilus W-7. • Fengycin B inhibits Phytophthora infestans mycelium growth in a direct manner. • Surfactin induces potato plant defense responses to control late blight.

Retinitis pigmentosa (RP) is a complex group of hereditary retinal dystrophies. Although >60 genes have been identified to be associated with non-syndromic RP, the exact genetic variant remains elusive in numerous cases of RP. In the present study, a Chinese pedigree affected by RP with autosomal recessive inheritance, including a total of seven members with one affected patient and six unaffected individuals, was recruited. Comprehensive ophthalmic examinations were performed on the proband and the proband's unaffected daughter. Genomic DNA was extracted from peripheral blood. Whole-exome sequencing (WES) was performed for the affected individual. The candidate pathogenic variant was verified by direct Sanger sequencing. The affected individual presented with classical clinical symptoms of RP. A novel homozygous variant, c.265delC (p.L89Ffs*3) in the cyclic nucleotide-gated channel subunit α 1 gene was identified in the affected patient. This homozygous variant was absent in other unaffected family members and 600 ethnicity-matched healthy controls. The variant was co-segregated with the disease phenotype in an autosomal recessive manner.

Parkinson's disease (PD), as one of the complex neurodegenerative disorders, affects millions of aged people. Although the precise pathogenesis remains mostly unknown, a significant number of studies have demonstrated that mitochondrial dysfunction acts as a major role in the pathogeny of PD. Both nuclear and mitochondrial DNA mutations can damage mitochondrial integrity. Especially, mutations in several genes that PD-linked have a closed association with mitochondrial dysfunction (e.g., Parkin, PINK1, DJ-1, alpha-synuclein, and LRRK2). Parkin, whose mutation causes autosomal-recessive juvenile parkinsonism, plays an essential role in mitochondrial quality control of mitochondrial biogenesis, mitochondrial dynamics, and mitophagy. Therefore, we summarized the advanced studies of Parkin's role in mitochondrial quality control and hoped it could be studied further as a therapeutic target for PD.

Spot blotch, caused by fungal pathogen Bipolaris sorokiniana Shoemaker, is one of the most frequent diseases affecting barley-growing regions worldwide. In this study, we reported the genome sequence of the highly virulent B. sorokiniana strain GN1 using the Illumina HiSeq 4000 platform. In total, 57 million 150-nucleotide paired-end clean reads were obtained and assembled into 96 scaffolds with an estimated genome size of 34.33 Mb. Furthermore, we identified genes that may be associated with strain-specific virulence and performed phylogenetic analysis of GN1 with five other Bipolaris spp. These results for GN1 will provide important information in understanding its molecular underpinning of pathogenicity and help identify novel sources of genetic resistance for improving disease resistance in barley.

Maxillofacial bone defects caused by multiple factors, including congenital deformations and tumors, have become a research focus in the field of oral medicine. Bone tissue engineering is increasingly regarded as a potential approach for maxillofacial bone repair. Mesenchymal stem cells (MSCs) with different origins display various biological characteristics. The aim of the present study was to investigate the effects of casein kinase‑2 interaction protein‑1 (CKIP‑1) on MSCs, including femoral bone marrow‑derived MSCs (BMMSCs) and orofacial bone‑derived MSCs (OMSCs), isolated from the femoral and orofacial bones of wild‑type (WT) and CKIP‑1 knockout (KO) mice. MSCs were isolated using collagenase II and the main biological characteristics, including proliferation, apoptosis and osteogenic differentiation, were investigated. Subcutaneous transplantation of MSCs in mice was also performed to assess ectopic bone formation. MTT and clone formation assay results indicated that cell proliferation in the KO group was increased compared with the WT group, and OMSCs exhibited significantly increased levels of proliferation compared with BMMSCs. However, the proportion of apoptotic cells was not significantly different between CKIP‑1 KO OMSCs and BMMSCs. Furthermore, it was revealed that osteogenic differentiation was increased in CKIP‑1 KO MSCs compared with WT MSCs, particularly in OMSCs. Consistent with the in vitro results, enhanced ectopic bone formation was observed in CKIP‑1 KO mice compared with WT mice, particularly in OMSCs compared with BMMSCs. In conclusion, the present results indicated that OMSCs may have a superior sensitivity to CKIP‑1 in promoting osteogenesis compared with BMMSCs; therefore, CKIP‑1 KO in OMSCs may serve as an efficient strategy for maxillofacial bone repair.

IκB kinase (IKK) is the core regulator of the nuclear factor-κB (NF-κB) pathway, which is involved in cellular development and proliferation, as well as the inflammatory response. IKKα is an important subunit of the IKK complex. In this study, two IKKαs (EcIKKα-1 and -2) were characterized in E. coioides. Similar to IKKα of other species, EcIKKα-1 and -2 contained a kinase domain, a leucine zipper, a helix-loop-helix domain and a beta NF-κB essential modulator-binding domain. Sequence alignment indicated that EcIKKα-1 and -2 shared high degrees of sequence identity with IKKs from other species (about 63%-96%). EcIKKα-1 and -2 are widely expressed in all tissues, but have different expression profiles in normal groupers. Additionally, EcIKKα-1 and -2 responded rapidly to Cryptocaryon irritans infection at the local infection site (i.e., gill tissue), but there was no significant change in EcIKKα-2 expression. In GS cells, EcIKKα-1 was uniformly distributed in the cytoplasm, while EcIKKα-2 was observed uniformly both in the cytoplasm and nucleus. Both EcIKKα-1 and -2 were found to activate NF-κB, but the luciferase activity of EcIKKα-2 was twice that of EcIKKα-1. In addition, EcIKKα-1 and -2 can regulate the expression of immune-related cytokines (IL-1β, IL-6, IL-8, IL-12 [p35 subunit], and TNF-α). These findings should prove helpful to further elucidate the innate immunity function of IKKα in fish.

Objective This study was aimed to identify prognostic factors in glioma by analysis of the gene expression and DNA methylation data. MethodsThe RNAseq and DNA methylation data associated with glioma were downloaded from GEO and TCGA databases to analyze the differentially expressed genes (DEGs) and methylated genes between tumor and normal tissues. Function and pathway analyses, co-expression network and survival analysis were performed based on these DEGs. The intersection genes of DEGs and differentially methylated genes were obtained followed by function analysis. Results Total 2190 DEGs were identified between tumor and normal tissues, which were significantly enriched in neuron differentiation associated functions, as well as ribosome pathway. There were 6186 methylation sites (2834 up-regulated and 3352 down-regulated) with significant differences in tumor vs. normal. In the constructed co-expression network, DPP6, MAPK10 and RPL3 were hub genes. Survival analysis of 20 DEGs obtained 18 prognostic genes, among which 9 were differentially methylated, such as LHFPL tetraspan subfamily member 3 (LHFPL3), cadherin 20 (CDH20), complexin 2 (CPLX2), and tenascin R (TNR). The intersection of DEGs and differentially methylated genes (632 genes) were significantly enriched in functions of neuron differentiation. Conclusion DPP6, MAPK10 and RPL3 may play important roles in tumorigenesis of glioma. Additionally, methylation of LHFPL3, CDH20, CPLX2, and TNR may serve as prognostic factors of glioma.

Saposhnikovia divaricata (Turcz.) Schischk., a perennial herb belonging to the family Umbelliferae, is widely distributed in Northeast Asia. Its dried root (Radix Saposhnikoviae) is used as a Chinese herbal medicine for the treatment of immune system, nervous system, and respiratory diseases. Phytochemical and pharmacological studies have shown that the main constituents of S. divaricata are chromones, coumarins, acid esters, and polyacetylenes, and these compounds exhibited significant anti-inflammatory, analgesic, antioxidant, antiproliferative, antitumor, and immunoregulatory activities. The purpose of this review is to provide comprehensive information on the botanical characterization and distribution, traditional use and ethnopharmacology, phytochemistry, and pharmacology of S. divaricata for further study concerning its mechanism of action and development of better therapeutic agents and health products from S. divaricata.

Volatile components in fresh leaves are involved in the regulation of many stress responses, such as insect damage, fungal infection and high temperature. However, the potential function of volatile components in hyperosmotic response is largely unknown. Here, we found that 7-day hyperosmotic treatment specifically led to the accumulation of (Z)-3-hexen-1-ol, (E)-2-hexenal and methyl salicylate. Transcriptome and qRT-PCR analyses suggested the activation of linolenic acid degradation and methyl salicylate processes. Importantly, exogenous (Z)-3-hexen-1-ol pretreatment dramatically enhanced the hyperosmotic stress tolerance of tea plants and decreased stomatal conductance, whereas (E)-2-hexenal and methyl salicylate pretreatments did not exhibit such a function. qRT-PCR analysis revealed that exogenous ABA induced the expressions of related enzyme genes, and (Z)-3-hexen-1-ol could up-regulate the expressions of many DREB and RD genes. Moreover, exogenous (Z)-3-hexen-1-ol tremendously induced the expressions of specific LOX and ADH genes within 24 h. Taken together, hyperosmotic stress induced (Z)-3-hexen-1-ol accumulation in tea plant via the activation of most LOX, HPL and ADH genes, while (Z)-3-hexen-1-ol could dramatically enhance the hyperosmotic stress tolerance via the decrease of stomatal conductance and MDA, accumulation of ABA and proline, activation of DREB and RD gene expressions, and probably positive feedback regulation of LOXs and ADHs. KEY MESSAGE: Hyperosmotic stress induced (Z)-3-hexen-1-ol accumulation in Camellia sinensis via the up-regulation of most LOX, HPL and ADH genes, while (Z)-3-hexen-1-ol could dramatically enhance the hyperosmotic stress tolerance via the decrease of stomatal conductance, accumulation of proline, activation of DREB and RD gene expressions, and probably positive feedback regulation of LOXs and ADHs.

Previous reports have shown that, when Verticillium dahliae localizes at the root surface, many microRNAs (miRNAs) were identified at the early induction stage. Here, we constructed two groups from two timepoints of small RNA (sRNA) in cotton root responses to V. dahliae at the later induction stage, pathogen localizing in the interior of root tissue. We identified 71 known and 378 novel miRNAs from six libraries of the pathogen-induced and the control sRNAs. Combined with degradome and sRNA sequencing, 178 corresponding miRNA target genes were identified, in which 40 target genes from differentially expressed miRNAs were primarily associated with oxidation-reduction and stress responses. More importantly, we characterized the cotton miR477-CBP60A module in the later response of the plant to V. dahliae infection. A β-glucuronidase fusion reporter and cleavage site analysis showed that ghr-miR477 directly cleaved the messenger RNA of GhCBP60A in the posttranscriptional process. The ghr-miR477-silencing decreased plant resistance to this fungus, while the knockdown of GhCBP60A increased plant resistance, which regulated GhICS1 expression to determine salicylic acid level. Our data documented that numerous later-inducible miRNAs in the plant response to V. dahliae, suggesting that these miRNAs play important roles in plant resistance to vascular disease.

Objectives: Bordetella pertussis is a highly contagious respiratory agent and is the causative pathogen of pertussis, which primarily affects children. Current diagnostic techniques for this pathogen have a variety of limitations including a long culture time, low bacterial load, and lack of specificity. Methods: This article reports the development of a one-tube nested quantitative real-time PCR assay using the locked nucleic acid (LNA) technique (LNA-OTN-q-PCR), targeting the BP485 gene and using a simple inexpensive extraction method. A total of 130 clinical samples from patients with clinically suspected pertussis, collected from the Children’s Hospital of Hebei, China, were tested by LNA-OTN-q-PCR assay. RT-PCR and two-step semi-nested PCR assays were performed in parallel for comparison. Results: Only strains of B. pertussis were identified as positive, whereas all of the remaining strains were appropriately identified as negative by the LNA-OTN-q-PCR assay. A single copy per reaction can be detected by the LNA-OTN-q-PCR assay. Additionally, the sensitivity of this method was 100 times that of the RT-PCR assay (100 copies per reaction). Sixty-three of the 130 clinical samples were detected positive by LNA-OTN-q-PCR assay; in contrast, RT-PCR was able to detect only 41 positive samples. Following this, all 63 samples were positively identified by two-step semi-nested PCR. Compared with the two-step semi-nested PCR assay, both the specificity and sensitivity of the LNA-OTN-q-PCR assay using purified DNA and crude extract were 100%. Conclusions: This assay was able to detect B. pertussis infection with high sensitivity and specificity. This test shows great potential as a promising technique to detect B. pertussis in both clinical laboratories and public health settings. Keywords: One-tube nested quantitative real-time PCR using the LNA technique, Bordetella pertussis, Simple extraction method

Phagocytic cells are activated to produce a large amount of reactive oxygen species (ROS) that kill pathogens quickly and efficiently through oxidation. NADPH oxidase is the main source of intracellular ROS. In the present study, five subunits of the phagocytic NADPH oxidase complex were identified in orange-spotted grouper (Epinephelus coioides). The open reading frame of grouper gp91phox, p22phox, p67phox, p47phox, and p40phox were 1,698 bp, 564 bp, 1,497 bp, 1,290 bp, and 1,050 bp, respectively, and encoded 565, 187, 498, 429, and 349 amino acids. Evolutionary analysis indicated that these proteins are evolutionarily homologous to the corresponding proteins of other fish and mammals, and contain conserved functional domains and sites that are important in mammals. In addition, real-time polymerase chain reaction analysis showed that the expression of these five genes was higher in immune-related tissues in normal grouper, and that these genes were up-regulated in gill and spleen after C. irritans infection, which suggests that these genes may be involved in the defense against C. irritans infection.

Herein we describe the discovery of A-1331852, a first-in-class orally active BCL-XL inhibitor that selectively and potently induces apoptosis in BCL-XL-dependent tumor cells. This molecule was generated by re-engineering our previously reported BCL-XL inhibitor A-1155463 using structure-based drug design. Key design elements included rigidification of the A-1155463 pharmacophore and introduction of sp3-rich moieties capable of generating highly productive interactions within the key P4 pocket of BCL-XL. A-1331852 has since been used as a critical tool molecule for further exploring BCL-2 family protein biology, while also representing an attractive entry into a drug discovery program.

Multiplex real‐time quantitative polymerase chain reaction (mRT‐qPCR) assay is commonly used to detect respiratory viruses, however, the sensitivity is limited for most reports. A panel of locked nucleic acid based multiplex closed one‐tube nested real‐time PCR (mOTNRT‐PCR) assay consisting of five separate internally controlled RT‐qPCR assays was developed for detection of 14 respiratory viruses. The sensitivity and reproducibility of mOTNRT‐PCR panel were evaluated using plasmid standards and the specificity was evaluated using clinical samples. The clinical performance of mOTNRT‐PCR panel was further evaluated with 468 samples collected from patients with an acute respiratory infection and compared with individual real‐time PCR (RT‐qPCR) assay. The analytical sensitivities of mOTNRT‐PCR panel ranged from 2 to 20 copies/reaction, and no cross‐reaction with common respiratory viruses was observed. The coefficients of variation of intra‐assay and inter‐assay were between 0.35% and 8.29%. Totally 35 clinical samples detected by mOTNRT‐PCR assay panel were missed by RT‐qPCR and confirmed true positive by sequencing of nested PCR products. The mOTNRT‐PCR assay panel provides a more sensitive and high‐throughput method for the detection of 14 respiratory viruses., Research Highlights A panel of mOTNRT‐PCR consisted of five separate internally controlled RT‐qPCR assay.Locked nucleic acid was used to develop the mOTNRT‐PCR assay panel.The sensitivity of mOTNRT‐PCR panel ranged from 2‐20copies/reaction using plasmid.mOTNRT‐PCR was more sensitive than reported individual RT‐qPCR assay.

We introgressed wheatgrass germplasm from the octoploid amphiploid Triticum aestivum× Lophopyrum elongatum into wheat by manipulating the wheat Ph1 gene and discovered and characterized 130 introgression lines harboring single or, in various combinations, complete and recombined L. elongatum chromosomes. Diploid wheatgrass Lophopyrum elongatum (genomes EE) possesses valuable traits for wheat genetics and breeding. We evaluated several strategies for introgression of this germplasm into wheat. To detect it, we developed and validated multiplexed sets of Sequenom MassARRAY single nucleotide polymorphism (SNP) markers, which differentiated disomic and monosomic L. elongatum chromosomes from wheat chromosomes. We identified 130 introgression lines (ILs), which harbored 108 complete and 89 recombined L. elongatum chromosomes. Of the latter, 59 chromosomes were recombined by one or more crossovers and 30 were involved in centromeric (Robertsonian) translocations or were telocentric. To identify wheat chromosomes substituted for or recombined with L. elongatum chromosomes, we genotyped the ILs with the wheat 90-K Infinium SNP array. We found that most of the wheat 90-K probes correctly detected their targets in the L. elongatum genome and showed that some wheat SNPs are ancient and had originated prior to the divergence of the wheat and L. elongatum lineages. Of the 130 ILs, 52% were homozygous for Ph1 deletion and thus are staged to be recombined further. We failed to detect in the L. elongatum genome the 4/5 reciprocal translocation that has been reported in Thinopyrum bessarabicum and several other Triticeae genomes.

Proteins of the bromodomain and extra-terminal (BET) domain family are epigenetic readers that bind acetylated histones through their bromodomains to regulate gene transcription. Dual-bromodomain BET inhibitors (DbBi) that bind with similar affinities to the first (BD1) and second (BD2) bromodomains of BRD2, BRD3, BRD4 and BRDt have displayed modest clinical activity in monotherapy cancer trials. A reduced number of thrombocytes in the blood (thrombocytopenia) as well as symptoms of gastrointestinal toxicity are dose-limiting adverse events for some types of DbBi1–5. Given that similar haematological and gastrointestinal defects were observed after genetic silencing of Brd4 in mice6, the platelet and gastrointestinal toxicities may represent on-target activities associated with BET inhibition. The two individual bromodomains in BET family proteins may have distinct functions7–9 and different cellular phenotypes after pharmacological inhibition of one or both bromodomains have been reported10,11, suggesting that selectively targeting one of the bromodomains may result in a different efficacy and tolerability profile compared with DbBi. Available compounds that are selective to individual domains lack sufficient potency and the pharmacokinetics properties that are required for in vivo efficacy and tolerability assessment10–13. Here we carried out a medicinal chemistry campaign that led to the discovery of ABBV-744, a highly potent and selective inhibitor of the BD2 domain of BET family proteins with drug-like properties. In contrast to the broad range of cell growth inhibition induced by DbBi, the antiproliferative activity of ABBV-744 was largely, but not exclusively, restricted to cell lines of acute myeloid leukaemia and prostate cancer that expressed the full-length androgen receptor (AR). ABBV-744 retained robust activity in prostate cancer xenografts, and showed fewer platelet and gastrointestinal toxicities than the DbBi ABBV-07514. Analyses of RNA expression and chromatin immunoprecipitation followed by sequencing revealed that ABBV-744 displaced BRD4 from AR-containing super-enhancers and inhibited AR-dependent transcription, with less impact on global transcription compared with ABBV-075. These results underscore the potential value of selectively targeting the BD2 domain of BET family proteins for cancer therapy. ABBV-744, a selective inhibitor of the BD2 domains of BET family proteins, is effective against prostate cancer in mouse xenograft models, with lower toxicities than the dual-bromodomain BET inhibitor ABBV-075.

C-Raf proto-oncogene serine/threonine kinase is a mitogen-activated protein kinase (MAP) kinase kinase, which can initiate a mitogen-activated protein kinase (MAPK) cascade by phosphorylating the dual-specific MAP kinase kinases (MEK1/2), and in turn activate the extracellular signal-regulated kinases (ERK1/2). To study the function of c-Raf in teleost fish, a c-Raf cDNA sequence from orange-spotted grouper (Epinephelus coioides) was cloned. Ecc-Raf shared 81%–99% amino acid identity with other vertebrate c-Raf molecules, and shared the highest amino acid identity (99%) with Lates calcarifer c-Raf. Genomic structure analysis revealed that grouper c-Raf shared a conserved exon structure with other vertebrates. Tissue distribution showed that Ecc-Raf was mainly transcribed in systemic immune organs. Ecc-Raf was distributed throughout the cytoplasm of transfected GS cells and the overexpression of Ecc-Raf only slightly enhanced the activation of Activator protein 1. The phosphorylation levels of Ecc-Raf can be induced by PMA and H2O2 treatment, in contrast to DMSO or untreated HKLs. Moreover, the phosphorylation level of the Raf-MEK-ERK axis was downregulated after 24 h of SGIV infection. On the other hand, the total level and phosphorylation level of c-Raf significantly increased post C. irritans infection and showed an enhanced level post immunization. The results of this study suggested that the Raf-MEK-ERK cascade was involved in the response to viral or parasitic infections.

Tylorrhynchus heterochaetus is a widespread benthic polychaete worm found in coastal brackish waters of the west Pacific. It has high ecological and economic value as a biomarker of water quality and as a high-quality feed in aquaculture and fisheries and is considered a delicacy in some areas of Asia. However, it has experienced a marked reduction in recent years due to overexploitation as well as changes in the environment and climate. Here, to comprehensively understand its genetic background and thus provide insights for better conservation and utilization of this species, we assessed the genetic variability and demographic history of T. heterochaetus individuals sampled from eight locations along the coasts of southeast China and north Vietnam based on mitochondrial cytochrome c oxidase I ( COI) sequences. We observed high haplotype diversity ( Hd), with an average of 0.926, but relatively low nucleotide diversity ( π), with a mean of 0.032 across all samples. A total of 94 polymorphic sites and 85 haplotypes were identified among 320 individuals. The pairwise genetic distances among haplotypes ranged from 0.001 to 0.067, with the high intraspecific divergence possibly reflecting geographic isolation and gene pool fragmentation. Significant genetic structures were revealed among the studied locations; specifically, the eight locations could be treated as six genetically different populations based on pairwise Φ ST results (0.026-0.951, P

Microalgae have been reported in many studies with high biomass, high carbohydrate content, fast growth rate and multiple bio-activities, while Dictyosphaerium sp. was rarely studied. Polysaccharide prove to be remarkable in many biological activities. To optimize the effects of the ultrasonic-assisted extraction parameters on the yield of polysaccharide from Dictyosphaerium sp., a single-factor experiment and response surface methodology (RSM) with a central composite rotatable design were employed. Four independent variables were investigated: X1 (ratio of raw microalgal powder to water), X2 (extraction temperature), X3 (extraction time), X4 (extraction power). The optimal conditions obtained via single-factor experiment were: X1 (1:25), X2 (50 °C), X3 (50 min), X4 (500 W), while according to the analysis of RSM, the optimum conditions were: X1 (1:26), X2 (58 °C), X3 (55 min), X4 (525 W). The refined polysaccharide were further prepared and characterized using SEM, FT-IR, XRD and TGA/DSC. Five kinds of antioxidant assays were carried out and the results indicated that the refined polysaccharide had strong scavenging ability to DPPH· and OH·. This study provides theoretical and experimental basis for the development and utilization of microalgal resources.

Little is known about the association between lipoprotein(a) [Lp(a)] levels and future ischemic cardiovascular events in patients with premature acute coronary syndrome (ACS). A total of 1464 consecutive patients who underwent coronary angiography for premature ACS (males 79.3 nmol/L). Major adverse cardiovascular events (MACEs) increased with Lp(a) quartiles after 2-year follow-up (among quartiles, respectively; P = .001). Kaplan-Meier curves revealed significant differences in event-free survival rates among Lp(a) quartile groups ( P = .001). Multivariate Cox proportional hazards regression analysis indicated that serum Lp(a) level was an independent predictor of MACE either as a continuous variable (hazard ratio [HR]: 1.002, 95% confidence interval [CI]: 1.001-1.004; P = .009) or as a categorical variable (HR: 1.443, 95% CI: 1.074-1.937; P = .015). Furthermore, Lp(a) levels (as a variable) significantly improved the prognostic value for MACE. These findings suggest that Lp(a) measurement has value for cardiovascular risk stratification in patients with premature ACS.

Background Alzheimer’s disease (AD) is closely related to aging, showing an increasing incidence rate for years. As one of the main brain regions involved in AD, hippocampus has been extensively studied due to its association with many human diseases. However, little is known about its association with primary ciliary dyskinesia (PCD). Material and Methods The microarray data of hippocampus on AD were retrieved from the Gene Expression Omnibus (GEO) database to construct the co-expression network by weighted gene co-expression network analysis (WGCNA). The gene network modules associated with AD screened with the common genes were further annotated based on Gene Ontology (GO) database and enriched based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. The protein-protein interaction (PPI) network was constructed based on STRING database to identify the hub genes in the network. Results Genes involved in PCD were identified in the hippocampus of AD patients. Functional analysis revealed that these genes were mainly enriched in ciliary tissue, ciliary assembly, axoneme assembly, ciliary movement, microtubule based process, microtubule based movement, organelle assembly, axoneme dynamin complex, cell projection tissue, and microtubule cytoskeleton tissue. A total of 20 central genes, e.g., DYNLRB2, ZMYND10, DRC1, DNAH5, WDR16, TTC25, and ARMC4 were identified as hub genes related to PCD in hippocampus of AD patients. Conclusion Our study demonstrated that AD and PCD have common metabolic pathways. These common pathways provide novel evidence for further investigation of the pathophysiological mechanism and the hub genes suggest new therapeutic targets for the diagnosis and treatment of AD and PCD. Subjects Bioinformatics, Cell Biology, Molecular Biology, Neurology.

Emerging studies have indicated that the consumption of rice could be the major methylmercury (MeHg) contributor to human mercury (Hg) exposure. Nonetheless, few studies are available on Hg in rice around the world, especially in countries with heavy rice diet. In this study, total Hg (THg) and MeHg levels in rice samples (n = 172) across Nepal were first investigated. The geometric mean THg was 7.05 ± 7.71 µg/kg with a range of 0.622 µg/kg to 158 µg/kg, and the maximum THg level was up to 791% of the Chinese National Standard Limit for THg in rice (20 µg/kg). The geometric mean MeHg was 0.820 ± 0.660 µg/kg with a range of 0.189 µg/kg to 8.59 µg/kg. Overall, the mean MeHg exposure (0.00445 ± 0.00477 µg/kg bw/day) and inorganic Hg (IHg) exposure (0.0360 ± 0.0739 µg/kg bw/day) were lower than the reference dose (RfD) of 0.1 µg/kg bw/day for MeHg and the provisional tolerable weekly intake (PTWI) of 0.571 µg/kg bw/day for IHg, respectively. Concerning different groups of vulnerable populations, the highest MeHg exposure (0.126 µg/kg bw/day) and IHg exposure (1.57 µg/kg bw/day) of preschoolers (37–50 months old) were approximately 126% of the RfD for MeHg and 275% of the PTWI for IHg. When the pregnant mothers eat the rice without awareness of the Hg content in rice, the mean and highest intelligence quotients (IQs) losses were 9554 and 118659 points, respectively, and the corresponding economic costs due to IQ loss could be 15.1 million USD and 188 million USD in Nepal. The results of rice THg and MeHg levels and corresponding exposure in populations highlighted the occurrence of rice THg and MeHg pollution issues in Nepal. More efforts should be made to protect younger groups in Nepal from high rice Hg exposure. Capsule Owing to the high rice consumption rates relative to body mass, preschoolers (37–50 months) may meet the 126% reference dose (0.1 µg/kg bw/day) for MeHg and 275% provisional tolerable weekly intake (0.571 µg/kg bw/day) for IHg exposure in Nepal.

The perennial grass Cenchrus spinifex (common sandbur) is an invasive species that grows in arid and semi-arid regions due to its remarkable phenotypic plasticity, which confers the ability to withstand drought and other forms of abiotic stress. Exploring the molecular mechanisms of drought tolerance in common sandbur could lead to the development of new strategies for the protection of natural and agricultural environments from this weed. To determine the molecular basis of drought tolerance in C. spinifex, we used isobaric tags for relative and absolute quantitation (iTRAQ) to identify proteins differing in abundance between roots growing in normal soil and roots subjected to moderate or severe drought stress. The analysis of these proteins revealed that drought tolerance in C. spinifex primarily reflects the modulation of core physiological activities such as protein synthesis, transport and energy utilization as well as the accumulation of flavonoid intermediates and the scavenging of reactive oxygen species. Accordingly, plants subjected to drought stress accumulated sucrose, fatty acids, and ascorbate, shifted their redox potential (as determined by the NADH/NAD ratio), accumulated flavonoid intermediates at the expense of anthocyanins and lignin, and produced less actin, indicating fundamental reorganization of the cytoskeleton. Our results show that C. spinifex responds to drought stress by coordinating multiple metabolic pathways along with other adaptations. It is likely that the underlying metabolic plasticity of this species plays a key role in its invasive success, particularly in semi-arid and arid environments.

Teleosts show varied master sex determining (MSD) genes and sex determination (SD) mechanisms, with frequent turnovers of sex chromosomes. Tracing the origins of MSD genes and turnovers of sex chromosomes in a taxonomic group is of particular interest in evolutionary biology. Oyster pompano ( Trachinotus anak ), a marine fish, belongs to the family Carangidae, in which 17b-hydroxysteroid dehydrogenase 1 ( hsd17b1 ) has repeatedly evolved to an MSD gene. Whole-genome resequencing identified a single nucleotide polymorphism (SNP) at chromosome 24 to be strictly associated with phenotypic sex, with females being the heterozygous sex. This SNP is located in a splicing site at the first exon/intron boundary of hsd17b1 . The Z-linked SNP results in malfunction of all spliced isoforms, whereas the W-linked isoforms were predicted to have open reading frames that are conserved among vertebrates, suggesting that hsd17b1 is a female-determining gene. The differential alternative splicing patterns of ZZ and ZW genotypes were consistently observed both in undifferentiated stages and differentiated gonads. We observed elevated recombination around the SD locus and no differentiation between Z and W chromosomes. The extreme diversity of mutational mechanisms that hsd17b1 evolves to an MSD gene highlights frequent in situ turnovers between sex chromosomes in the Carangidae.

The regulation of glucose-stimulated insulin secretion and glucose excursion has a sensory component that operates in a sex-dependent manner. Objective Here, we aim to dissect the basis of the sexually dimorphic interaction between sensory neurons and pancreatic β cells and its overall impact on insulin release and glucose homeostasis. Methods We used viral retrograde tracing techniques, surgical and chemodenervation models, and primary cell-based co-culture systems to uncover the biology underlying sex differences in sensory modulation of pancreatic β-cell activity. Results Retrograde transsynaptic labeling revealed a sex difference in the density of sensory innervation in the pancreas. The number of sensory neurons emanating from the dorsal root and nodose ganglia that project in the pancreas is higher in male than in female mice. Immunostaining and confocal laser scanning microscopy confirmed the higher abundance of peri-islet sensory axonal tracts in the male pancreas. Capsaicin-induced sensory chemodenervation concomitantly enhanced glucose-stimulated insulin secretion and glucose clearance in male mice. These metabolic benefits were blunted when mice were orchidectomized prior to the ablation of sensory nerves. Interestingly, orchidectomy also lowered the density of peri-islet sensory neurons. In female mice, capsaicin treatment did not affect glucose-induced insulin secretion nor glucose excursion and ovariectomy did not modify these outcomes. Interestingly, same- and opposite-sex sensory-islet co-culture paradigms unmasked the existence of potential gonadal hormone-independent mechanisms mediating the male-female difference in sensory modulation of islet β-cell activity. Conclusion Taken together, these data suggest that the sex-biased nature of the sensory control of islet β-cell activity is a result of a combination of neurodevelopmental inputs, sex hormone-dependent mechanisms and the potential action of somatic molecules encoded by the sex chromosome complement., Highlights • Pancreas-projecting sensory neurons are more abundant in males than in females. • Male sex hormones regulate the density of peri-islet sensory innervation in adulthood. • Male sex hormones regulate sensory modulation of β-cell activity and glucose clearance. • Sex chromosome mechanisms regulate sensory modulation of islet β-cell activity.

Cervical adenocarcinoma is an important disease that affects young women and it has a high mortality and poor prognosis. Denticleless E3 ubiquitin protein ligase homolog (DTL) gene with oncogenic function has been evaluated in several cancers. Through this study, we aimed to clarify the clinical and molecular characteristics of cervical adenocarcinoma involving overexpression of DTL and elucidate its molecular mechanism. Bioinformatics analysis was performed through multiple databases. RNA sequencing was used to obtain differentially expressed genes after DTL was overexpressed in cells. The role of DTL in cervical adenocarcinoma was explored through in vitro and in vivo experiments. We found that DTL has an unfavorable prognostic implication for patients with cervical adenocarcinoma. Overexpression of DTL induced the migration and invasion of tumor cells in vitro and promoted intra-pulmonary metastasis in vivo. In addition, DTL activated JNK through RAC1 and upregulated FOXO1 to induce epithelial–mesenchymal transition, and the migration and invasion of tumor cells. Therefore, we conclude that overexpression of DTL enhanced cell motility and promoted tumor metastasis of cervical adenocarcinoma by regulating the RAC1-JNK-FOXO1 axis. These results suggest that DTL may become a potential therapeutic target for antitumor metastasis of cervical adenocarcinoma.

A novel chitosan-modified kiwi branch biochar (CHKB) was successfully fabricated as cut-price modified biochar to remove Cd (II) from wastewater. Characterization experiments with SEM-EDS, FTIR and XPS suggested that CHKB had more cations and surface functional groups compared with the original kiwi biochar (KB). The adsorption experiment results of Cd (II) on CHKB showed that the adsorption isotherms can be described best by the Langmuir model and that the pseudo-second-order model fits the Cd (II) adsorption kinetics well, indicating that the process was monolayer and controlled by chemisorption. CHKB exhibited the Langmuir maximum adsorption capacity of Cd (II) (126.58 mg g-1), however, that of KB is only 4.26 mg g-1. The adsorption ability of CHKB was improved by the increase of the surface area and abundant surface functional groups (-OH, -NH, C=O and so on). And the cation exchange, electrostatic interaction, surface complexation and precipitation were main mechanisms in the sorption of Cd (II) on CHKB. In addition, CHKB can be regenerated and reused for Cd (II) sorption by the eluent of EDTA-2Na. Excellent adsorption performance, low-cost, and environmental-friendly made CHKB become the fantastic adsorbent to remove Cd (II) in wastewater.

The role of neutrophils in bone regeneration remains elusive. In this study, it is shown that intramuscular implantation of interleukin‐8 (IL‐8) (commonly recognized as a chemotactic cytokine for neutrophils) at different levels lead to outcomes resembling those of fracture hematoma at various stages. Ectopic endochondral ossification is induced by certain levels of IL‐8, during which neutrophils are recruited to the implanted site and are N2‐polarized, which then secrete stromal cell‐derived factor‐1α (SDF‐1α) for bone mesenchymal stem cell (BMSC) chemotaxis via the SDF‐1/CXCR4 (C‐X‐C motif chemokine receptor 4) axis and its downstream phosphatidylinositol 3'‐kinase (PI3K)/Akt pathway and β‐catenin‐mediated migration. Neutrophils are pivotal for recruiting and orchestrating innate and adaptive immunocytes, as well as BMSCs at the initial stage of bone healing and regeneration. The results in this study delineate the mechanism of neutrophil‐initiated bone regeneration and interaction between neutrophils and BMSCs, and innate and adaptive immunities. This work lays the foundation for research in the fields of bone regenerative therapy and biomaterial development, and might inspire further research into novel therapeutic options., Following inflammatory stimuli at the bone defect site, neutrophils arrive first, recruit and orchestrate innate and adaptive immunocytes and BMSCs to initiate endochondral ossification under the appropriate immune environment. In this process, N2‐polarized neutrophils mediate anti‐inflammatory transformation of macrophages and CD4+ T cells, secrete SDF‐1α for BMSC chemotaxis via the SDF‐1/CXCR4 axis and its downstream PI3K/AKT pathway and β‐catenin‐mediated migration.

This work aims to analyze and construct a novel competing endogenous RNA (ceRNA) network in ankylosing spondylitis (AS) with bone bridge formation, lncRNA. Using RNA sequencing and bioinformatics, we analyzed expression profiles of long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and mRNAs in whole blood cells from 5 AS patients and 3 healthy individuals. Next, we verified the expression levels of candidate lncRNAs in 97 samples using the ΔΔCt value of real-time quantitative polymerase chain reaction (qRT-PCR). We used multivariate logistic regression analysis to screen lncRNAs and clinical indicators for use in the prediction model. Both SPSS 24.0 and R software were used for data analysis and prediction model construction. The results showed that compared with the normal controls, 205 long noncoding RNAs (lncRNAs), 961 microRNAs (miRNAs), and 200 mRNAs (DEmRNAs) were differentially expressed in the AS patients. We identified lncRNA 122K13.12 and lncRNA 326C3.7 among 205 lncRNAs differentially expressed between AS patients and healthy humans. Then, we noted that 30 miRNAs and five mRNAs formed a ceRNA network together with these two lncRNAs. These ceRNA networks might regulate the tumor necrosis factor (TNF) signaling pathway in AS development. In addition, the expression level of lncRNA 122K13.12 and lncRNA 326C3.7 correlated with various structural damage indicators in AS. Specifically, the lncRNA 326C3.7 expression level was an independent risk factor in bone bridge formation [area under the ROC curve (AUC) = 0.739 (0.609–0.870) and p = 0.003], and the best Youden Index was 0.405 (sensitivity = 0.800 and specificity = 0.605). Moreover, we constructed a lncRNA-based nomogram that could effectively predict bone bridge formation [AUC = 0.870 (0.780–0.959) and p < 0.001, and the best Youden Index was 0.637 (sensitivity = 0.900 and specificity = 0.737)]. In conclusion, we uncovered a unique ceRNA signaling network in AS with bone bridge formation and identified novel biomarkers and prediction models with the potential for clinical applications.