As an important method for building blocks synthesis, whole cell biocatalysis is hindered by some shortcomings such as unpredictability of reactions, utilization of opportunistic pathogen, and side reactions. Due to its biological and extensively studied genetic background, Pseudomonas putida KT2440 is viewed as a promising host for construction of efficient biocatalysts. After analysis and reconstruction of the lactate utilization system in the P. putida strain, a novel biocatalyst that only exhibited NAD-independent D-lactate dehydrogenase activity was prepared and used in L-2-hydroxy-carboxylates production. Since the side reaction catalyzed by the NAD-independent L-lactate dehydrogenase was eliminated in whole cells of recombinant P. putida KT2440, two important L-2-hydroxy-carboxylates (L-lactate and L-2-hydroxybutyrate) were produced in high yield and high optical purity by kinetic resolution of racemic 2-hydroxy carboxylic acids. The results highlight the promise in biocatalysis by the biotechnologically important organism P. putida KT2440 through genomic analysis and recombination.

Interferon-chi (IFN-χ) is a type of function-unknown IFN. IFN-χ in bovines (BoIFN-χ) has evolved as a multigene family. This family comprises four IFN-χ subtypes, two of which are functional genes, which we demonstrated to (i) have antiviral and antiproliferative activities, (ii) be highly sensitive to trypsin, and (iii) remain stable with changes in pH and temperature. BoIFN-χ is a key intermediate in antiviral response, PAbs against BoIFN-χs could downregulate the transcriptional activation of ISGs induced by poly(I:C), and BoIFN-χs could be induced upon virus infection at the early and late phase. Additionally, BoIFN-χs bind with type-I IFN receptors, induce transcription of interferon regulatory factor 7 (IRF7), interferon-stimulated genes (ISGs), and type-I IFNs as well as myxovirus resistance protein 1 (Mx1) expression. Expression of ISGs and activation of IFN-stimulated response element (ISRE) induced with BoIFN-χs could be downregulated significantly by the Janus kinase (JAK) 1 and signal transducers and activators of transcription (STAT) 1 inhibitor. The promoters of BoIFN-β, nuclear factor-kappa B, and ISRE could be activated with BoIFN-χs, and the BoIFN-χ promoter could be activated by other type-I IFNs. Overall, BoIFN-χ could be induced with virus infection and signal through the JAK-STAT pathway to form a positive-feedback regulation of IFN production. These findings may facilitate further research on the role of IFN-χ in innate immune responses.

Population-based estimates of the impact of gender throughout the whole course of brain metastases (BMs) at the time of diagnosis of systemic malignancies are insufficient. We aimed to discover the influence of gender on the presence of BMs in newly diagnosed malignancies and the survival of those patients on a population-based level.

The prevalence of clinical multidrug-resistant (MDR) Pseudomonas aeruginosa has been increasing rapidly worldwide over the years and responsible for a wide range of acute and chronic infections with high mortalities. Although hundreds of complete genomes of clinical P. aeruginosa isolates have been sequenced, only a few complete genomes of mucoid strains are available, limiting a comprehensive understanding of this important group of opportunistic pathogens. Herein, the complete genome of a clinically isolated mucoid strain P. aeruginosa JNQH-PA57 was sequenced and assembled using Illumina and Oxford nanopore sequencing technologies. Genomic features, phylogenetic relationships, and comparative genomics of this pathogen were comprehensively analyzed using various bioinformatics tools. A series of phenotypic and molecular-genetic tests were conducted to investigate the mechanisms of carbapenem resistance in this strain.

Age-related macular degeneration (AMD) is a leading cause of blindness. Laser-induced nonhuman primate choroidal neovascularization (CNV) is a widely used animal model of neovascular AMD. Subretinal fibrosis (SFb) is the major limiting factor of effective anti-VEGF therapy for neovascular AMD, yet SFb has never been systematically analyzed in the primate CNV model and if VEGF directly affect SFb is unknown. We recruited a large cohort of rhesus macaques to study the occurrence, multimodal imaging and electroretinography (ERG) features, and related cytokines of SFb. Here we show that among 33 rhesus macaques, 88% CNV eyes developed SFb. Spectral domain optical coherence tomography (SD-OCT) identified four types of subretinal hyper-reflective material (SHRM) of SFb in primate. Multimodal imaging is reliable for monitoring SFb and matches the histological results well. Reduced amplitude of oscillatory potentials correlates with the thinning of inner retina layers and is a possible SFb indicator. Iba1+ microglia/macrophage cells infiltrated in the fibrotic lesions, and aqueous cytokine analysis identified four fibrosis-related factors (GM-CSF, IL-10, TGFβ2 and VEGF). Unexpectedly, we found sustained expression of VEGF may be an important inducer of SFb, and anti-VEGF therapy actually partially suppresses SFb. Taken together, our data suggest the laser-induced primate SFb model, coupled with multimodal imaging and ERG recording, is a useful system to dissect the pathogenesis and explore the rationale of treatment for SFb; and combined therapy with anti-VEGF and anti-fibrosis agents is necessary for AMD treatment.

In-stent restenosis (ISR) is one of the most important complications and impacts the long-term effects after percutaneous coronary intervention (PCI) in patients with coronary heart disease (CHD). Related studies have revealed that microRNA (miRNA) can predict ISR in CHD patients. MiRNA-126 may be a potential biomarker for the diagnosis of ISR. However, the accuracy of miRNA-126 in the diagnosis of ISR is still controversial. Therefore, this study carried out meta-analysis to further evaluate the accuracy of miRNA-126 in the diagnosis of ISR. At the same time, bioinformatics is used to predict the target genes and miRNA-126 may be involved in regulation, so as to provide theoretical support for the precise treatment of CHD.

To investigate the effective components and possible mechanism of action of Lavandula angustifolia Mill. essential oil (LEO) in preventing vomiting through the olfactory pathway.

Sprouty-related, EVH1 domain-containing protein 1 (SPRED1) has been identified as a novel tumor suppressor gene in acute myeloid leukemia (AML). Previous studies showed that SPRED1 methylation levels were significantly increased in AML patients, making it an interesting candidate for further investigations. To confirm the association of SPRED1 methylation, clinical parameters, and known molecular prognosticators and to identify the impact of methylation level on treatment outcome, we conducted this study in a larger cohort of 75 AML patients. Significantly increased methylation levels of SPRED1 were detected at four of ten CpG units by quantitative high-resolution mass spectrometry-based approach (MassARRAY) in AML patients. Whereas overall survival (OS) and relapse-free survival (RFS) showed no statistical difference between hypermethylation and hypomethylation subgroups, the relationship between methylation level and treatment response was indicated in paired samples from pre- and post-induction. To determine the possible mechanism of SPRED1 methylation in AML, we performed in vitro experiments using THP-1 cells, as the latter showed the highest methylation level (determined by utilizing bisulfite modification) among the three AML cell lines we tested. When treated with 5-AZA and lentivirus transfection, upregulated SPRED1 expression, decreased cell proliferation, increased cell differentiation and apoptosis, and inactivated phosphorylated extracellular signal-regulated kinase (p-ERK) were detected in THP-1 cells. These results show that demethylation of SPRED1 can inhibit the proliferation of AML cells and promote their differentiation and apoptosis, possibly by the ERK pathway. The hypermethylation of SPRED1 is a potential therapeutic target for AML.

For developing an effective interventional approach and treatment modality for PM2.5, the effects of omega-3 fatty acids on alleviating inflammation and attenuating lung injury induced by inhalation exposure of PM2.5 were assessed in murine models. We found that daily oral administration of the active components of omega-3 fatty acids, docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA) effectively alleviated lung parenchymal lesions, restored normal inflammatory cytokine levels and oxidative stress levels in treating mice exposed to PM2.5 (20 mg/kg) every 3 days for 5 times over a 14-day period. Especially, CT images and the pathological analysis suggested protective effects of DHA and EPA on lung injury. The key molecular mechanism is that DHA and EPA can inhibit the entry and deposition of PM2.5, and block the PM2.5-mediated cytotoxicity, oxidative stress, and inflammation.

High soil salinity seriously affects plant growth and development. Excessive salt ions mainly cause damage by inducing osmotic stress, ion toxicity, and oxidation stress. Casuarina equisetifolia is a highly salt-tolerant plant, commonly grown as wind belts in coastal areas with sandy soils. However, little is known about its physiology and the molecular mechanism of its response to salt stress.

Tigecycline serves as one of the last-resort antibiotics to treat severe infections caused by carbapenem-resistant Enterobacterales. Recently, a novel plasmid-mediated resistance-nodulation-division (RND)-type efflux pump gene cluster, TmexCD1-ToprJ1, and its variants, TmexCD2-ToprJ2 and TmexCD3-ToprJ3, encoding tetracyclines and tigecycline resistance, were revealed. In this study, we reported three TmexCD2-ToprJ2-harboring Klebsiella species strains, collected from two teaching tertiary hospitals in China, including one K. quasipneumoniae, one K. variicola, and one K. michiganensis. The three strains were characterized by antimicrobial susceptibility testing (AST), conjugation assay, WGS, and bioinformatics analysis. AST showed that K. variicola and K. quasipneumoniae strains were resistant to tigecycline with MIC values of 4μg/ml, whereas the K. michiganensis was susceptible to tigecycline with an MIC value of 1μg/ml. The TmexCD2-ToprJ2 clusters were located on three similar IncHI1B plasmids, of which two co-harbored the metallo-β-lactamase gene bla NDM-1. Conjugation experiments showed that all three plasmids were capable of self-transfer via conjugation. Our results showed, for the first time, that this novel plasmid-mediated tigecycline resistance mechanism TmexCD2-ToprJ2 has spread into different Klebsiella species, and clinical susceptibility testing may fail to detect. The co-occurrence of bla NDM-1 and TmexCD2-ToprJ2 in the same plasmid is of particular public health concern as the convergence of "mosaic" plasmids can confer both tigecycline and carbapenem resistance. Its further spread into other clinical high-risk Klebsiella clones will likely exacerbate the antimicrobial resistance crisis. A close monitoring of the dissemination of TmexCD-ToprJ encoding resistance should be considered.

Precancerous lesions of gastric cancer (PLGC) refer to a kind of histopathological changes in the gastric mucosa that can progress to gastric cancer. Elian granules (ELG), a Chinese medicinal prescription, have achieved satisfactory results in the treatment of PLGC. However, the exact mechanism underlying the therapeutic effect of ELG remains unclear. Here, this study aims to explore the mechanism of ELG alleviating PLGC in rats.

The sucrose non-fermentation-related protein kinase (SnRK) is a kind of Ser/Thr protein kinase, which plays a crucial role in plant stress response by phosphorylating the target protein to regulate the interconnection of various signaling pathways. However, little is known about the SnRK family in Eucalyptus grandis. Thirty-four putative SnRK sequences were identified in E. grandis and divided into three subgroups (SnRK1, SnRK2 and SnRK3) based on phylogenetic analysis and the type of domain. Chromosome localization showed that SnRK family members are unevenly distributed in the remaining 10 chromosomes, with the notable exception of chromosome 11. Gene structure analysis reveal that 10 of the 24 SnRK3 genes contained no introns. Moreover, conserved motif analyses showed that SnRK sequences belonged to the same subgroup that contained the same motif type of motif. The Ka/Ks ratio of 17 paralogues suggested that the EgrSnRK gene family underwent a purifying selection. The upstream region of EgrSnRK genes enriched with different type and numbers of cis-elements indicated that EgrSnRK genes are likely to play a role in the response to diverse stresses. Quantitative real-time PCR showed that the majority of the SnRK genes were induced by salt treatment. Genome-wide analyses and expression pattern analyses provided further understanding on the function of the SnRK family in the stress response to different environmental salt concentrations.

Open Kasai portoenterostomy (KPE) remains the mainstay of treatment for biliary atresia (BA) even in the era of minimally invasive surgery and is generally considered to be technically challenging. This study describes the learning curve (LC) of open KPE and its effect on outcomes.

Scrub typhus, a serious public health problem in the Asia-Pacific area, is endemic in the "tsutsugamushi triangle" area. Scrub typhus has been widespread and has become a significant health concern in China. However, spatiotemporal patterns need to be investigated further.

The association between genetic variations and immunotherapy benefit has been widely recognized, while such evidence in gastrointestinal cancer remains limited. We analyzed the genomic profile of 227 immunotherapeutic gastrointestinal cancer patients treated with immunotherapy, from the Memorial Sloan Kettering (MSK) Cancer Center cohort. A gastrointestinal immune prognostic signature (GIPS) was constructed using LASSO Cox regression. Based on this signature, patients were classified into two subgroups with distinctive prognoses (p < 0.001). The prognostic value of the GIPS was consistently validated in the Janjigian and Pender cohort (N = 54) and Peking University Cancer Hospital cohort (N = 92). Multivariate analysis revealed that the GIPS was an independent prognostic biomarker. Notably, the GIPS-high tumor was indicative of a T-cell-inflamed phenotype and immune activation. The findings demonstrated that GIPS was a powerful predictor of immunotherapeutic survival in gastrointestinal cancer and may serve as a potential biomarker guiding immunotherapy treatment decisions.

MYB transcription factors are a kind of DNA binding protein that can specifically interact with the promoter region. Members of MYB TFs are widely involved in plant growth and development, secondary metabolism, stress response, and hormone signal transduction. However, there is no report of comprehensive bioinformatics analysis on the MYB family of Casuarina equisetifolia.

Evidence reveals that microRNA (miRNA) can predict coronary restenosis in patients suffering from coronary heart disease (CHD) after percutaneous coronary intervention (PCI). Perhaps, miRNA-21 is a promising biomarker for the diagnosis of coronary restenosis after PCI. However, the accuracy of miRNA-21 has not been systematically evaluated. Therefore, it is necessary to perform meta-analysis to certify the diagnostic values of miRNA-21 on coronary restenosis after PCI.

Members of the amino acid/auxin permease (AAAP) gene family play indispensable roles in various plant metabolism and biosynthesis processes. Comprehensive analysis of AAAP genes has been conducted in Arabidopsis, rice, maize and poplar, but has not been reported from moso bamboo. Phylogenetics, evolutionary patterns and further expression profiles analysis of the AAAP gene family in moso bamboo (Phyllostachys edulis) will increase our understanding of this important gene family.

To assess the metabolites associated with Pseudomonas aeruginosa infection by analyzing the microbial diversity and metabolomics in lower respiratory tract of bronchiectasis patients and to explore the therapeutic approaches for Pseudomonas aeruginosa infection.