The Snf5-Hsf1 transcription module synergistically regulates stress responses and pathogenicity by maintaining ROS homeostasis in Sclerotinia sclerotiorum.

The SWI/SNF complex is guided to the promoters of designated genes by its co-operator to activate transcription in a timely and appropriate manner to govern development, pathogenesis, and stress responses in fungi. Nevertheless, knowledge of the complexes and their co-operator in phytopathogenic fungi is still fragmented. We demonstrate that the heat shock transcription factor SsHsf1 guides the SWI/SNF complex to promoters of heat shock protein (hsp) genes and antioxidant enzyme genes using biochemistry and pharmacology. This is accomplished through direct interaction with the complex subunit SsSnf5 under heat shock and oxidative stress. This results in the activation of their transcription and mediates histone displacement to maintain reactive oxygen species (ROS) homeostasis. Genetic results demonstrate that the transcription module formed by SsSnf5 and SsHsf1 is responsible for regulating morphogenesis, stress tolerance, and pathogenicity in Sclerotinia sclerotiorum, especially by directly activating the transcription of hsp genes and antioxidant enzyme genes counteracting plant-derived ROS. Furthermore, we show that stress-induced phosphorylation of SsSnf5 is necessary for the formation of the transcription module. This study establishes that the SWI/SNF complex and its co-operator cooperatively regulate the transcription of hsp genes and antioxidant enzyme genes to respond to host and environmental stress in the devastating phytopathogenic fungi.

Preoperative Discrimination of CDKN2A/B Homozygous Deletion Status in Isocitrate Dehydrogenase-Mutant Astrocytoma: A Deep Learning-Based Radiomics Model Using MRI.

BACKGROUND: Cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) homozygous deletion has been verified as an independent and critical biomarker of negative prognosis and short survival in isocitrate dehydrogenase (IDH)-mutant astrocytoma. Therefore, noninvasive and accurate discrimination of CDKN2A/B homozygous deletion status is essential for the clinical management of IDH-mutant astrocytoma patients. PURPOSE: To develop a noninvasive, robust preoperative model based on MR image features for discriminating CDKN2A/B homozygous deletion status of IDH-mutant astrocytoma. STUDY TYPE: Retrospective. POPULATION: Two hundred fifty-one patients: 107 patients with CDKN2A/B homozygous deletion and 144 patients without CDKN2A/B homozygous deletion. FIELD STRENGTH/SEQUENCE: 3.0 T/1.5 T: Contrast-enhanced T1-weighted spin-echo inversion recovery sequence (CE-T1WI) and T2-weighted fluid-attenuation spin-echo inversion recovery sequence (T2FLAIR). ASSESSMENT: A total of 1106 radiomics and 1000 deep learning features extracted from CE-T1WI and T2FLAIR were used to develop models to discriminate the CDKN2A/B homozygous deletion status. Radiomics models, deep learning-based radiomics (DLR) models and the final integrated model combining radiomics features with deep learning features were developed and compared their preoperative discrimination performance. STATISTICAL TESTING: Pearson chi-square test and Mann Whitney U test were used for assessing the statistical differences in patients' clinical characteristics. The Delong test compared the statistical differences of receiver operating characteristic (ROC) curves and area under the curve (AUC) of different models. The significance threshold is P < 0.05. RESULTS: The final combined model (training AUC = 0.966; validation AUC = 0.935; test group: AUC = 0.943) outperformed the optimal models based on only radiomics or DLR features (training: AUC = 0.916 and 0.952; validation: AUC = 0.886 and 0.912; test group: AUC = 0.862 and 0.902). DATA CONCLUSION: Whether based on a single sequence or a combination of two sequences, radiomics and DLR models have achieved promising performance in assessing CDKN2A/B homozygous deletion status. However, the final model combining both deep learning and radiomics features from CE-T1WI and T2FLAIR outperformed the optimal radiomics or DLR model. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.

Pantoea jilinensis D25 enhances tomato salt tolerance via altering antioxidant responses and soil microbial community structure.

As a major challenge to global food security, soil salinity is an important abiotic stress factor that seriously affects the crop growth and yield. In this study, the mechanism of salt resistance of Pantoea jilinensis D25 and its improving effect on salt tolerance of tomato were explored with salt resistance-related genes identified in strain D25 by genomic sequencing. The results showed that in comparison with the treatment of NaCl, strain D25 significantly increased the fresh weight, shoot length, root length, and chlorophyll content of tomato under salt stress by 46.7%, 20%, 42.4%, and 44.2%, respectively, with increased absorptions of various macronutrients and micronutrients and decreased accumulation of Na+. The activities of defense enzymes (peroxidase, catalase, superoxide dismutase, phenylalanine ammonia-lyase, and polyphenol oxidase) were enhanced, while the content of malondialdehyde was decreased. The results of quantitative real-time PCR analysis showed that the expressions of genes (SlSOS1, SlNHX1, SlHKT1.1, SlSOD1, SlAPX2, SlAOS, SlPin II, Solyc08g066270.1, Solyc03g083420.2 and SlGA20ox1) related to ion transporters, antioxidant machinery, key defense, serine/threonine protein kinase synthesis, and gibberellin (GA) signal protein were up-regulated and were the highest in the treatment of both NaCl and strain D25. The activities of enzymes (dehydrogenase, urease, invertase, and catalase activities) related to soil fertility were enhanced. The results of 16S rRNA sequencing showed that soil microbial diversity and the abundance of probiotics (e.g., Acidibacter, Limnobacter, and Romboutsia) were significantly increased. Our study provided strong experimental evidence to support the agricultural application of strain D25 in the promotion of growth in crops.

Finite element analysis of precise puncture vertebral augmentation in the treatment of different types of osteoporotic vertebral compression fractures.

BACKGROUND: Osteoporosis vertebral compression fracture (OVCF) secondary to osteoporosis is a common health problem in the elderly population. Vertebral augmentation (VA) has been widely used as a minimally invasive surgical method. The transpedicle approach is commonly used for VA puncture, but sometimes, it is limited by the anatomy of the vertebral body and can not achieve good surgical results. Therefore, we propose the treatment of OVCF with precise puncture vertebral augmentation (PPVA). This study used finite element analysis to explore the biomechanical properties of PPVA in the treatment of osteoporotic vertebral compression fractures (OVCFs) with wedge, biconcave, and collapse deformities. METHOD: Three-dimensional finite element models of the fractured vertebral body and adjacent superior and inferior vertebral bodies were established using Computed Tomography (CT) data from patients with OVCF, both before and after surgery. Evaluate the stress changes of the wedged deformed vertebral body, biconcave deformed vertebral body, collapsed deformed vertebral body, and adjacent vertebral bodies before and after PPVA. RESULT: In vertebral bodies with wedge deformity and collapsed deformity, PPVA can effectively reduce the stress on the vertebral body but increases the stress on the vertebral body with biconcave deformity. PPVA significantly decreases the stress on the adjacent vertebral bodies of the wedge deformed vertebral body, and decreases the stress on the adjacent superior vertebral body of biconcave deformity and collapsed deformed vertebral bodies, but increases the stress on the adjacent inferior vertebral bodies. PPVA improves the stress distribution of the vertebral body and prevents high-stress areas from being concentrated on one side of the vertebral body. CONCLUSION: PPVA has shown positive surgical outcomes in treating wedge deformed and collapsed deformed vertebral bodies. However, its effectiveness in treating biconcave vertebral body is limited. Furthermore, PPVA has demonstrated favorable results in addressing adjacent superior vertebral body in three types of fractures.

Biomechanical study between percutaneous vertebroplasty combined with cement pedicle plasty improves vertebral biomechanical stability: A finite element analysis.

OBJECTIVE: To investigate the biomechanical effects of percutaneous vertebroplasty combined with cement pedicle plasty (PVCPP) on the unstable osteoporotic vertebral fractures (OVFs) through finite element (FE) analysis. The study compares the biomechanical stability of finite element models between percutaneous vertebroplasty (PVP) and percutaneous vertebroplasty combined with cement pedicle plasty. METHODS: Two patients with unstable OVFs underwent computed tomography (CT) examination at the thoracolumbar vertebral body levels, respectively. The CT images were reconstructed into three-dimensional finite element models to simulate stress conditions across six dimensions and to evaluate the vertebral von Mises stress before and after bone cement reinforcement. RESULTS: The study found that stress distribution differed between groups mainly at the pedicle base. In the surgical vertebral bodies, the maximum stress in the PVP group decreased during flexion and left bending, while it increased in other states. In the PVCPP group, all maximum stresses decreased. In the inferior vertebral bodies, the maximum stress in the PVP group generally increased, while it decreased in the PVCPP group. In the superior vertebral bodies, postoperatively, the maximum stress in the PVP group generally increased, while it almost remained unchanged in the PVCPP group. PVP group had higher cement stress and displacement. CONCLUSION: PVCPP is an effective treatment method for patients with unstable OVFs. It can quickly relieve pain and enhance the stability of the three columns, thereby reducing the risk of some complications.

PLIC11 drives lung cancer progression through regulating the YY1/PIWIL4 axis.

Lung cancer is the leading cause of cancer related deaths worldwide. Nonsmall cell lung cancers (NSCLC), the most common histological type of lung cancer, are known to be less well characterized. Long noncoding RNAs are a new class of cancer regulators. Here, we aimed to investigate the effect of lncRNA PLIC11 in NSCLC progression. In our study, we found that PLIC11 was upregulated in lung cancer, particularly in metastatic lung cancer tissues. Overexpression of PLIC11 enhanced cell proliferation, migration, and metastasis in vitro and in vivo. Mechanically, PLIC11 could interact with YY1 and promote PIWIL4 expression by transcription activation. Therefore, PLIC11 upregulation is a potential indicator of aggressive lung cancer, Silencing of PLIC11 has great potential therapeutic strategy in NSCLC.

Multicenter clinical radiomics-integrated model based on [18F]FDG PET and multi-modal MRI predict ATRX mutation status in IDH-mutant lower-grade gliomas.

OBJECTIVES: To develop a clinical radiomics-integrated model based on 18 F-fluorodeoxyglucose positron emission tomography ([18F]FDG PET) and multi-modal MRI for predicting alpha thalassemia/mental retardation X-linked (ATRX) mutation status of IDH-mutant lower-grade gliomas (LGGs). METHODS: One hundred and two patients (47 ATRX mutant-type, 55 ATRX wild-type) diagnosed with IDH-mutant LGGs (CNS WHO grades 1 and 2) were retrospectively enrolled. A total of 5540 radiomics features were extracted from structural MR (sMR) images (contrast-enhanced T1-weighted imaging, CE-T1WI; T2-weighted imaging, and T2WI), functional MR (fMR) images (apparent diffusion coefficient, ADC; cerebral blood volume, CBV), and metabolic PET images ([18F]FDG PET). The random forest algorithm was used to establish a clinical radiomics-integrated model, integrating the optimal multi-modal radiomics model with three clinical parameters. The predictive effectiveness of the models was evaluated by receiver operating characteristic (ROC) and decision curve analysis (DCA). RESULTS: The optimal multi-modal model incorporated sMR (CE-T1WI), fMR (ADC), and metabolic ([18F]FDG) images ([18F]FDG PET+ADC+ CE-T1WI) with the area under curves (AUCs) in the training and test groups of 0.971 and 0.962, respectively. The clinical radiomics-integrated model, incorporating [18F]FDG PET+ADC+CE-T1WI, three clinical parameters (KPS, SFSD, and ATGR), showed the best predictive effectiveness in the training and test groups (0.987 and 0.975, respectively). CONCLUSIONS: The clinical radiomics-integrated model with metabolic, structural, and functional information based on [18F]FDG PET and multi-modal MRI achieved promising performance for predicting the ATRX mutation status of IDH-mutant LGGs. KEY POINTS: • The clinical radiomics-integrated model based on [18F]FDG PET and multi-modal MRI achieved promising performance for predicting ATRX mutation status in LGGs. • The study investigated the value of multicenter clinical radiomics-integrated model based on [18F]FDG PET and multi-modal MRI in LGGs regarding ATRX mutation status prediction. • The integrated model provided structural, functional, and metabolic information simultaneously and demonstrated with satisfactory calibration and discrimination in the training and test groups (0.987 and 0.975, respectively).

CDK12 loss inhibits cell proliferation by regulating TBK1 in non-small cell lung cancer cells.

Lung cancer is one of the most common malignant tumors and has a poor prognosis and a low survival rate. Traditional treatments, such as radiotherapy and chemotherapy, still face some challenges because of high drug resistance and toxicity. Therefore, it is necessary to discover a new kind of targeted drug with low toxicity and high efficiency. CDK12 is a cell cycle-dependent kinase whose main function is to activate RNA polymerase II (RNAPII) and promote the transcriptional extension of RNA. However, the role and molecular mechanism of CDK12 in lung cancer are still unclear. In this study, the mutation and RNA-Seq data of CDK12 in lung adenocarcinoma and squamous cell carcinoma were downloaded from The Cancer Genome Atlas (TCGA) database and analyzed with the custom scripts. Cell proliferation was evaluated by Cell Counting Kit-8 (CCK-8) and cell colony formation assays. A subcutaneous tumor experiment in nude mice was used to examine the effects of CDK12 knockdown on the in vivo tumor growth of NSCLC cells. The cell cycle distribution and the apoptosis rate of lung cancer cells were assessed by flow cytometry. Regulation of TANK-binding kinase 1 (TBK1) by CDK12 was evaluated by quantitative PCR, immunoprecipitation and Western blot analysis. In this study we have analyzed the mutation and expression data of The Cancer Genome Atlas (TCGA) database and found that CDK12 is highly expressed in lung cancer tissues. Clinical correlation analysis showed that high expression of CDK12 in NSCLC reduces patient survival, but its high expression is only related to early tumor progression and has no significant correlation with late tumor progression and metastasis. Furthermore, we present evidence that CDK12 depletion in lung cancer cell lines not only leads to the inhibition of cell growth and induces apoptosis but also inhibits tumor growth of NSCLC cells in vivo. CDK12 positively regulates the expression of the oncogene TBK1 in lung cancer cells. These results revealed that CDK12 affects the progression of non-small cell lung cancer through positive regulation of TBK1 expression, suggesting that CDK12 might be a potential molecular target for the treatment of non-small cell lung cancer.

Antifungal activity of Klebsiella grimontii DR11 against Fusarium oxysporum causing soybean root rot.

AIMS: Soybean root rot, caused by Fusarium oxysporum, leads to significant economic and financial losses to the soybean processing industry globally. In the study, we aimed to explore a biocontrol agent to combat F. oxysporum infection in soybean. METHODS AND RESULTS: From soybean rhizosphere soil, 48 strains were isolated. Among them, the strain DR11 exhibited the highest inhibition rate of 72.27%. Morphological, physiological, biochemical, and 16S rDNA identification revealed that the strain DR11 was Klebsiella grimontii DR11. Strain DR11 could inhibit the growth of F. oxysporum and spore formation and alter the mycelial morphology. At 5.0 × 106 CFU mL-1, pH 7, and 30°C, it exhibited the highest inhibitory rate (72.27%). Moreover, it could decrease the activity of cell-wall-degrading enzymes of F. oxysporum. Simultaneously, the activities of defense-related enzymes and content of malondialdehyde in soybean plants were increased after treatment with strain DR11. In addition, strain DR11 could form aggregates to form biofilm and adsorb on the surface of soybean roots. It inhibited F. oxysporum growth on soybean seedlings, with an inhibitory effect of 62.71%. CONCLUSION: Klebsiella grimontii DR11 had a strong inhibitory effect on F. oxysporum and could be used as a biocontrol agent to combat F. oxysporum infection in soybean.

DYNC1H1 regulates NSCLC cell growth and metastasis by IFN-γ-JAK-STAT signaling and is associated with an aberrant immune response.

It is urgent to identify new biomarkers and therapeutic targets to ameliorate the clinical prognosis of patients with lung cancer. The functional significance and molecular mechanism of dynein cytoplasmic 1 heavy chain 1 (DYNC1H1) in nonsmall cell lung cancer (NSCLC) progression is still elusive. In our current study, publicly available data and Western blotting experiments confirmed that DYNC1H1 expression was upregulated in lung cancer samples compared with noncancerous samples. Quantitative real-time PCR (qPCR) results indicated that high DYNC1H1 expression in lung cancer tissues was significantly associated with clinical tumor stage and distal metastasis; moreover, its high expression was negatively correlated with prognosis. Functional experiments demonstrated that DYNC1H1 loss of function caused a significant decrease in cell viability and cell proliferative ability, inhibition of the cell cycle, and promotion of both migration potential and invasion potential in vitro. Animal experiments by tail vein injection of lung cancer cells showed that DYNC1H1 knockdown significantly decreased lung cancer metastasis. Mechanistically, the results from a human protein array showed changes in the IFN-γ-JAK-STAT signaling pathway, and analysis of The Cancer Genome Atlas (TCGA) immune data demonstrated that disturbance of the immune microenvironment might be involved in the impaired growth and metastatic ability mediated by DYNC1H1 loss in NSCLC. DYNC1H1 might serve as a promising biological marker of prognosis and a potential clinical therapeutic target for patients with NSCLC.

The Autophagy Genes ChATG4 and ChATG8 Are Required for Reproductive Development, Virulence, and Septin Assembly in Cochliobolus heterostrophus.

Autophagy is a highly conserved degrading process that is crucial for cell growth and development in eukaryotes, especially when they face starvation and stressful conditions. To evaluate the functions of Atg4 and Atg8 in mycelial growth, asexual and sexual development, and virulence in Cochliobolus heterostrophus, ΔChatg4 and ΔChatg8 mutants were generated by gene replacement. Strains deleted for ChATG4 and ChATG8 genes showed significant changes in vegetative growth and development of conidia and ascospores compared with the wild-type strain. The autophagy process was blocked and virulence was reduced dramatically in ΔChatg4 and ΔChatg8 mutants. In addition, deletion of ChATG4 and ChATG8 disordered Cdc10 subcellular localization and formation of septin rings. The direct physical interaction between ChAtg4 and ChAtg8 was detected by yeast two-hybrid assay, and ChAtg4-GFP was dispersed throughout the cytoplasm, although GFP-ChAtg8 appeared as punctate structures. All phenotypes were restored in complemented strains. Taken together, these findings indicate that ChATG4 and ChATG8 are crucial for autophagy to regulate fungal growth, development, virulence, and localization of septin in C. heterostrophus.

The C2H2 Transcription Factor SsZFH1 Regulates the Size, Number, and Development of Apothecia in Sclerotinia sclerotiorum.

Sclerotinia sclerotiorum is a notorious phytopathogenic Ascomycota fungus with a host range of >600 plant species worldwide. This homothallic Leotiomycetes species reproduces sexually through a multicellular apothecium that produces and releases ascospores. These ascospores serve as the primary inoculum source for disease initiation in the majority of S. sclerotiorum disease cycles. The regulation of apothecium development for this pathogen and other apothecium-producing fungi remains largely unknown. Here, we report that a C2H2 transcription factor, SsZFH1 (zinc finger homologous protein), is necessary for the proper development and maturation of sclerotia and apothecia in S. sclerotiorum and is required for the normal growth rate of hyphae. Furthermore, ΔSszfh1 strains exhibit decreased H2O2 accumulation in hyphae, increased melanin deposition, and enhanced tolerance to H2O2 in the process of vegetative growth and sclerotia formation. Infection assays on common bean leaves, with thin cuticles, and soybean and tomato leaves, with thick cuticles, suggest that the deletion of Sszfh1 slows the mycelial growth rate, which in turn affects the expansion of leaf lesions. Collectively, our results provide novel insights into a major fungal factor mediating maturation of apothecia with additional effects on hyphae and sclerotia development.

Multi-Omics Techniques for Analysis Antifungal Mechanisms of Lipopeptides Produced by Bacillus velezensis GS-1 against Magnaporthe oryzae In Vitro.

Magnaporthe oryzae is a fungal pathogen that causes rice blast, a highly destructive disease. In the present study, the bacteria strain GS-1 was isolated from the rhizosphere soil of ginseng and identified as Bacillus velezensis through 16S rRNA gene sequencing, whole genome assembly, and average nucleotide identity analysis. B. velezensis strain GS-1 exhibited significant antagonistic activity to several plant fungal pathogens. Through whole genome sequencing, 92 Carbohydrate-Active Enzymes and 13 gene clusters that encoded for secondary metabolites were identified. In addition, strain GS-1 was able to produce the lipopeptide compounds, surfactin, fengycin, and plantazolicin. The inhibitory effects of lipopeptide compounds on M. oryzae were confirmed, and the antagonistic mechanism was explored using transcriptomics and metabolomics analysis. Differential expressed genes (DEGs) and differential accumulated metabolites (DAMs) revealed that the inhibition of M. oryzae by lipopeptide produced by GS-1 downregulated the expression of genes involved in amino acid metabolism, sugar metabolism, oxidative phosphorylation, and autophagy. These results may explain why GS-1 has antagonistic activity to fungal pathogens and revealed the mechanisms underlying the inhibitory effects of lipopeptides produced by GS-1 on fungal growth, which may provide a theoretical basis for the potential application of B. velezensis GS-1 in future plant protection.

Simulation of stray radiation from optical window with temperature-dependent spectral properties.

Stray radiation analysis coupled with a temperature field is performed for a semitransparent window, focusing on the temperature-dependent optical properties. The transient temperature response of the optical window-based encapsulation structure is first investigated under an external transient high-heat flux loading. The spectral selectivity of the window to thermal radiation is involved. Subsequently, several typical cases for stray radiation are conducted, considering the inhomogeneous optical properties caused by the temperature heterogeneity. It is found that the stray radiation distribution is more chaotic compared to the results with optical properties independent of temperature. In addition, the stray radiation power has a large deviation (150%) if one neglects the temperature dependence. Meanwhile, the difference in wave band power decreases with the wavelength rising. Additionally, the stray radiation power generated by the window is far less in the visible wave band than that in the near-infrared wave band. The results reveal that the temperature dependence in optical properties of a semitransparent window should be seriously considered when calculating the stray radiation, especially in high-precision detection devices.

Preparative isolation of the major metabolite NK-1375 of diamide insecticide cyclaniliprole and its application to pertinent residue analysis in plant-origin foods using UHPLC-MS/MS.

NK-1375 is a major metabolite of the diamide insecticide cyclaniliprole (CYCP) with toxicological significance. It is formed in various transformation pathways of CYCP, including photolysis and plant metabolism. In the present study, NK-1375 was produced employing the liquid-phase photolysis of CYCP followed by isolation using preparative liquid chromatography. The structure of the isolated substance was confirmed using MS and 1 H NMR spectroscopy, and its purity was measured to be 95.9% using HPLC. As its application, a residue analysis method was first developed for the simultaneous determination of CYCP and NK-1375 in six representative plant-origin foods using fast multi-plug filtration cleanup and UHPLC-MS/MS. Excellent linearity (r > 0.999) was obtained over the calibration range from 0.001 to 0.1 µg mL-1 . The recoveries (intra-day and inter-day) of CYCP and NK-1375 from different matrices ranged from 74 to 112%, with corresponding relative standard deviations less than 13%. The limits of quantitation of these two compounds were defined at 0.01 mg kg-1 . This study can be useful for the subsequent analytical or toxicological research on this important pesticide metabolite.

GsSnRK1 interplays with transcription factor GsERF7 from wild soybean to regulate soybean stress resistance.

Although the function and regulation of SnRK1 have been studied in various plants, its molecular mechanisms in response to abiotic stresses are still elusive. In this work, we identified an AP2/ERF domain-containing protein (designated GsERF7) interacting with GsSnRK1 from a wild soybean cDNA library. GsERF7 gene expressed dominantly in wild soybean roots and was responsive to ethylene, salt, and alkaline. GsERF7 bound GCC cis-acting element and could be phosphorylated on S36 by GsSnRK1. GsERF7 phosphorylation facilitated its translocation from cytoplasm to nucleus and enhanced its transactivation activity. When coexpressed in the hairy roots of soybean seedlings, GsSnRK1(wt) and GsERF7(wt) promoted plants to generate higher tolerance to salt and alkaline stresses than their mutated species, suggesting that GsSnRK1 may function as a biochemical and genetic upstream kinase of GsERF7 to regulate plant adaptation to environmental stresses. Furthermore, the altered expression patterns of representative abiotic stress-responsive and hormone-synthetic genes were determined in transgenic soybean hairy roots after stress treatments. These results will aid our understanding of molecular mechanism of how SnRK1 kinase plays a cardinal role in regulating plant stress resistances through activating the biological functions of downstream factors.

Down-regulated expression of microRNA-338-5p contributes to neuropathology in Alzheimer's disease.

Alzheimer's disease (AD) is a leading cause of dementia. However, the mechanisms responsible for development of AD, especially for the sporadic variant, are still not clear. In our previous study, we discovered that a small noncoding RNA (miR-188-3p) targeting ß-site amyloid precursor protein cleaving enzyme (BACE)-1, a key enzyme responsible for Aß formation, plays an important role in the development of neuropathology in AD. In the present study, we identified that miR-338-5p, a new miRNA that also targets BACE1, contributes to AD neuropathology. We observed that expression of miR-338-5p was significantly down-regulated in the hippocampus of patients with AD and 5XFAD transgenic (TG) mice, an animal model of AD. Overexpression of miR-338-5p in the hippocampus of TG mice reduced BACE1 expression, Aß formation, and neuroinflammation. Overexpression of miR-338-5p functionally prevented impairments in long-term synaptic plasticity, learning ability, and memory retention in TG mice. In addition, we provide evidence that down-regulated expression of miR-338-5p in AD is regulated through the NF-κB signaling pathway. Our results suggest that down-regulated expression of miR-338-5p plays an important role in the development of AD.-Qian, Q., Zhang, J., He, F.-P., Bao, W.-X., Zheng, T.-T., Zhou, D.-M., Pan, H.-Y., Zhang, H., Zhang, X.-Q., He, X., Sun, B.-G., Luo, B.-Y., Chen, C., Peng, G.-P. Down-regulated expression of microRNA-338-5p contributes to neuropathology in Alzheimer's disease.

Successful biosynthesis of natural antioxidant ergothioneine in Saccharomyces cerevisiae required only two genes from Grifola frondosa.

BACKGROUND: Ergothioneine (EGT) has a unique antioxidant ability and diverse beneficial effects on human health. But the content of EGT is very low in its natural producing organisms such as Mycobacterium smegmatis and mushrooms. Therefore, it is necessary to highly efficient heterologous production of EGT in food-grade yeasts such as Saccharomyces cerevisiae. RESULTS: Two EGT biosynthetic genes were cloned from the mushroom Grifola frondosa and successfully heterologously expressed in Saccharomyces cerevisiae EC1118 strain in this study. By optimization of the fermentation conditions of the engineered strain S. cerevisiae EC1118, the 11.80 mg/L of EGT production was obtained. With daily addition of 1% glycerol to the culture medium in the fermentation process, the EGT production of the engineered strain S. cerevisiae EC1118 can reach up to 20.61 mg/L. CONCLUSION: A successful EGT de novo biosynthetic system of S. cerevisiae containing only two genes from mushroom Grifola frondosa was developed in this study. This system provides promising prospects for the large scales production of EGT for human health.

DCUN1D1 facilitates tumor metastasis by activating FAK signaling and up-regulates PD-L1 in non-small-cell lung cancer.

E3 ubiquitin ligases, which are key enzymes in the ubiquitin proteasome system, catalyze the ubiquitination of proteins to target them for proteasomal degradation. Emerging evidence suggests that E3 ubiquitin ligases play important roles in the development and progression of lung cancer. In our study, we characterized the gene expression landscape of lung cancer using data obtained from TCGA to explore the changes in E3 ubiquitin ligase containing the regulators of E3 ubiquitin ligase activity. Overall, most gene expression changes occurred in NSCLC tissues compared with adjacent normal ones. In total, 48 E3 ubiquitin ligases containing the regulators were up-regulated in NSCLC tissues compared with their levels in normal tissues. We analyzed the expression of up-regulated E3 ubiquitin ligases containing the regulators in two publicly available transcriptome data sets (GSE13213 and GSE30219). We found that four E3 ubiquitin ligases (UHRF1, BRCA1, TRAIP and HLTF) and one regulator of ubiquitin E3 activity DCUN1D1 that were dramatically up-regulated in cancer were significantly associated with tumor metastasis and patient's poor prognosis both in two transcriptome data sets. Next, clinical analysis indicated that the expression levels of DCUN1D1 correlated with clinical stage and lymph node metastasis in NSCLC patients as determined by quantitative reverse transcription-PCR. Furthermore, functional assays showed that DCUN1D1 promoted NSCLC cell invasion and migration as determined by transwell assay in vitro. Mechanistically, we found that the C-terminal Cullin binding domain leads to oncogenic activity and the UBA domain acts as a negative regulator of DCUN1D1 function in NSCLC. Moreover, DCUN1D1 activated the FAK oncogenic signaling pathway and up-regulated PD-L1. Taken together, our results demonstrate that DCUN1D1 is a metastasis regulator and suggest a new therapeutic option for NSCLC metastasis.

Transcriptomic analysis of Chlorimuron-ethyl degrading bacterial strain Klebsiella jilinsis 2N3.

Chlorimuron-ethyl is a sulfonylurea herbicide with a long residual period in the field and is toxic to rotational crops. Klebsiella jilinsis 2N3 is a gram-negative bacterium that can rapidly degrade Chlorimuron-ethyl. In this study, the gene expression changes in strain 2N3 during degradation of Chlorimuron-ethyl was analyzed by RNA-Seq. Results showed that 386 genes were up-regulated and 453 genes were down-regulated. KEGG pathway enrichment analysis revealed the highest enrichment ratio in the pathway of sulfur metabolism. On the basis of the functional annotation and gene expression, we predicted that carboxylesterase, monooxygenase, glycosyltransferase, and cytochrome P450 were involved in the metabolism of Chlorimuron-ethyl biodegradation. Results of qRT-PCR showed that the relative mRNA expression levels of these genes were higher in treatment group than those in control group. The cytochrome P450 encoded by Kj-CysJ and the alkanesulfonate monooxygenase encoded by Kj-SsuD were predicted and further experimentally confirmed by gene knockout as the key enzymes in the biodegradation process. Cultured in basal medium containing Chlorimuron-ethyl (5  mg L-1) in 36 h, the strains of ΔKj-CysJ, ΔKj-SsuD, and WT reached the highest OD600 values of 0.308, 0.873, and 1.085, and the highest degradation rates of Chlorimuron-ethyl of 11.83%, 96.21%, and 95.62%, respectively.