Observing astrocyte polarization in brains from mouse chronically infected with Toxoplasma gondii.

Toxoplasma gondii (T. gondii) is a protozoan parasite that infects approximately one-third of the global human population, often leading to chronic infection. While acute T. gondii infection can cause neural damage in the central nervous system and result in toxoplasmic encephalitis, the consequences of T. gondii chronic infection (TCI) are generally asymptomatic. However, emerging evidence suggests that TCI may be linked to behavioral changes or mental disorders in hosts. Astrocyte polarization, particularly the A1 subtype associated with neuronal apoptosis, has been identified in various neurodegenerative diseases. Nevertheless, the role of astrocyte polarization in TCI still needs to be better understood. This study aimed to establish a mouse model of chronic TCI and examine the transcription and expression levels of glial fibrillary acidic protein (GFAP), C3, C1q, IL-1α, and TNF-α in the brain tissues of the mice. Quantitative real-time PCR (qRT-PCR), enzyme-linked immunosorbent assay, and Western blotting were employed to assess these levels. Additionally, the expression level of the A1 astrocyte-specific marker C3 was evaluated using indirect fluorescent assay (IFA). In mice with TCI, the transcriptional and expression levels of the inflammatory factors C1q, IL-1α, and TNF-α followed an up-down-up pattern, although they remained elevated compared to the control group. These findings suggest a potential association between astrocyte polarization towards the A1 subtype and synchronized changes in these three inflammatory mediators. Furthermore, immunofluorescence assay (IFA) revealed a significant increase in the A1 astrocytes (GFAP+C3+) proportion in TCI mice. This study provides evidence that TCI can induce astrocyte polarization, a biological process that may be influenced by changes in the levels of three inflammatory factors: C1q, IL-1α, and TNF-α. Additionally, the release of neurotoxic substances by A1 astrocytes may be associated with the development of TCI.

Motion-artifact-augmented pseudo-label network for semi-supervised brain tumor segmentation.

MRI image segmentation is widely used in clinical practice as a prerequisite and a key for diagnosing brain tumors. The quest for an accurate automated segmentation method for brain tumor images, aiming to ease clinical doctors' workload, has gained significant attention as a research focal point. Despite the success of fully supervised methods in brain tumor segmentation, challenges remain. Due to the high cost involved in annotating medical images, the dataset available for training fully supervised methods is very limited. Additionally, medical images are prone to noise and motion artifacts, negatively impacting quality. In this work, we propose MAPSS, a motion-artifact-augmented pseudo-label network for semi-supervised segmentation. Our method combines motion artifact data augmentation with the pseudo-label semi-supervised training framework. We conduct several experiments under different semi-supervised settings on a publicly available dataset BraTS2020 for brain tumor segmentation. The experimental results show that MAPSS achieves accurate brain tumor segmentation with only a small amount of labeled data and maintains robustness in motion-artifact-influenced images. We also assess the generalization performance of MAPSS using the Left Atrium dataset. Our algorithm is of great significance for assisting doctors in formulating treatment plans and improving treatment quality.

Efficient biostimulation of microbial dechlorination of polychlorinated biphenyls by acetate and lactate under nitrate reducing conditions: Insights into dechlorination pathways and functional genes.

Microbial-catalyzed reductive dechlorination of polychlorinated biphenyls (PCBs) is largely affected by the indigenous sediment geochemical properties. In this study, the effects of nitrate on PCB dechlorination and microbial community structures were first investigated in Taihu Lake sediment microcosms. And biostimulation study was attempted supplementing acetate/lactate. PCB dechlorination was apparently inhibited under nitrate-reducing conditions. Lower PCB dechlorination rate and less PCB dechlorination extent were observed in nitrate amended sediment microcosms (T-N) than those in non-nitrate amended microcosms (T-1) during 66 weeks of incubation. The total PCB mass reduction in T-N was 17.6% lower than that in T-1. The flanked-para dechlorination was completely inhibited, while the ortho-flanked meta dechlorination was only partially inhibited in T-N. The 7.5 mM of acetate/lactate supplementation recovered PCB dechlorination by resuming ortho-flanked meta dechlorination. Repeated additions of lactate showed more effective biostimulation than acetate. Phylum Chloroflexi, containing most known PCB dechlorinators, was found to play a vital role on stability of the network structures. In T-N, putative dechlorinating Chloroflexi, Dehalococcoides and RDase genes rdh12, pcbA4, pcbA5 all declined. With acetate/lactate supplementation, Dehalococcoides grew by 1-2 orders of magnitude and rdh12, pcbA4, pcbA5 increased by 1-3 orders of magnitude. At Week 66, parent PCBs declined by 86.4% and 80.9% respectively in T-N-LA and T-N-AC compared to 69.9% in T-N. These findings provide insights into acetate/lactate biostimulation as a cost-effective approach for treating PCB contaminated sediments undergoing nitrate inhibition.

Multimodal radiomics based on 18F-Prostate-specific membrane antigen-1007 PET/CT and multiparametric MRI for prostate cancer extracapsular extension prediction.

OBJECTIVES: To compare the performance of the multiparametric magnetic resonance imaging (mpMRI) radiomics and 18F-Prostate-specific membrane antigen (PSMA)-1007 PET/CT radiomics model in diagnosing extracapsular extension (EPE) in prostate cancer (PCa), and to evaluate the performance of a multimodal radiomics model combining mpMRI and PET/CT in predicting EPE. METHODS: We included 197 patients with PCa who underwent preoperative mpMRI and PET/CT before surgery. mpMRI and PET/CT images were segmented to delineate the regions of interest and extract radiomics features. PET/CT, mpMRI, and multimodal radiomics models were constructed based on maximum correlation, minimum redundancy, and logistic regression analyses. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC) and indices derived from the confusion matrix. RESULTS: AUC values for the mpMRI, PET/CT, and multimodal radiomics models were 0.85 (95% CI, 0.78-0.90), 0.73 (0.64-0.80), and 0.83 (0.75-0.89), respectively, in the training cohort and 0.74 (0.61-0.85), 0.62 (0.48-0.74), and 0.77 (0.64-0.87), respectively, in the testing cohort. The net reclassification improvement demonstrated that the mpMRI radiomics model outperformed the PET/CT one in predicting EPE, with better clinical benefits. The multimodal radiomics model performed better than the single PET/CT radiomics model (P < .05). CONCLUSION: The mpMRI and 18F-PSMA-PET/CT combination enhanced the predictive power of EPE in patients with PCa. The multimodal radiomics model will become a reliable and robust tool to assist urologists and radiologists in making preoperative decisions. ADVANCES IN KNOWLEDGE: This study presents the first application of multimodal radiomics based on PET/CT and MRI for predicting EPE.

Suppression of long noncoding RNA SNHG6 alleviates cigarette smoke-induced lung inflammation by modulating NF-κB signaling.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a widespread inflammatory disease with a high mortality rate. Long noncoding RNAs play important roles in pulmonary diseases and are potential targets for inflammation intervention. METHODS: The expression of small nucleolar RNA host gene 6 (SNHG6) in mouse lung epithelial cell line MLE12 with or without cigarette smoke extract (CSE) treatment was first detected using quantitative reverse-transcription PCR. ELISA was used to evaluate the release of inflammatory cytokines (TNF-α, IL-1ß, and IL-6). The binding site of miR-182-5p with SNHG6 was predicted by using miRanda, which was verified by double luciferase reporter assay. RESULTS: Here, we revealed that SNHG6 was upregulated in CS-exposed MLE12 alveolar epithelial cells and lungs from COPD-model mice. SNHG6 silencing weakened CS-induced inflammation in MLE12 cells and mouse lungs. Mechanistic investigations revealed that SNHG6 could upregulate IκBα kinase through sponging the microRNA miR-182-5p, followed by activated NF-κB signaling. The suppressive effects of SNHG6 silencing on CS-induced inflammation were blocked by an miR-182-5p inhibitor. CONCLUSION: Overall, our findings suggested that SNHG6 regulates CS-induced inflammation in COPD by activating NF-κB signaling, thereby offering a novel potential target for COPD treatment.

Dual-Signal Chemical Exchange Saturation Transfer (Dusi-CEST): An Efficient Strategy for Visualizing Drug Delivery Monitoring in Living Cells.

We report a dual-signal chemical exchange saturation transfer (Dusi-CEST) strategy for drug delivery and detection in living cells. The two signals can be detected by operators in complex environments. This strategy is demonstrated on a cucurbit[6]uril (CB[6]) nanoparticle probe, as an example. The CB[6] probe is equipped with two kinds of hydrophobic cavities: one is found inside CB[6] itself, whereas the other exists inside the nanoparticle. When the probe is dispersed in aqueous solution as part of a hyperpolarized 129Xe NMR experiment, two signals appear at two different chemical shifts (100 and 200 ppm). These two resonances correspond to the NMR signals of 129Xe in the two different cavities. Upon loading with hydrophobic drugs, such as paclitaxel, for intracellular drug delivery, the two resonances undergo significant changes upon drug loading and cargo release, giving rise to a metric enabling the assessment of drug delivery success. The simultaneous change of Dusi-CEST likes a mobile phone that can receive both LTE and Wi-Fi signals, which can help reduce the occurrence of false positives and false negatives in complex biological environments and help improve the accuracy and sensitivity of single-shot detection.

Transcriptomic response for revealing the molecular mechanism of oat flowering under different photoperiods.

Proper flowering is essential for the reproduction of all kinds of plants. Oat is an important cereal and forage crop; however, its cultivation is limited because it is a long-day plant. The molecular mechanism by which oats respond to different photoperiods is still unclear. In this study, oat plants were treated under long-day and short-day photoperiods for 10 days, 15 days, 20 days, 25 days, 30 days, 40 days and 50 days, respectively. Under the long-day treatment, oats entered the reproductive stage, while oats remained vegetative under the short-day treatment. Forty-two samples were subjected to RNA-Seq to compare the gene expression patterns of oat under long- and short-day photoperiods. A total of 634-5,974 differentially expressed genes (DEGs) were identified for each time point, while the floral organ primordium differentiation stage showed the largest number of DEGs, and the spikelet differentiation stage showed the smallest number. Gene Ontology (GO) analysis showed that the plant hormone signaling transduction and hormone metabolism processes significantly changed in the photoperiod regulation of flowering time in oat. Moreover, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Mapman analysis revealed that the DEGs were mainly concentrated in the circadian rhythm, protein antenna pathways and sucrose metabolism process. Additionally, transcription factors (TFs) involved in various flowering pathways were explored. Combining all this information, we established a molecular model of oat flowering induced by a long-day photoperiod. Taken together, the long-day photoperiod has a large effect at both the morphological and transcriptomic levels, and these responses ultimately promote flowering in oat. Our findings expand the understanding of oat as a long-day plant, and the explored genes could be used in molecular breeding to help break its cultivation limitations in the future.

Transcriptome analysis of drought-responsive and drought-tolerant mechanisms in maize leaves under drought stress.

Maize is a major crop essential for food and feed, but its production is threatened by various biotic and abiotic stresses. Drought is one of the most common abiotic stresses, causing severe crop yield reduction. Although several studies have been devoted to selecting drought-tolerant maize lines and detecting the drought-responsive mechanism of maize, the transcriptomic differences between drought-tolerant and drought-susceptible maize lines are still largely unknown. In our study, RNA-seq was performed on leaves of the drought-tolerant line W9706 and the drought-susceptible line B73 after drought treatment. We identified 3147 differentially expressed genes (DEGs) between these two lines. The upregulated DEGs in W9706 were enriched in specific processes, including ABA signaling, wax biosynthesis, CHO metabolism, signal transduction and brassinosteroid biosynthesis-related processes, while the downregulated DEGs were enriched in specific processes, such as stomatal movement. Altogether, transcriptomic analysis suggests that the different drought resistances were correlated with the differential expression of genes, while the drought tolerance of W9706 is due to the more rapid response to stimulus, higher water retention capacity and stable cellular environment under water deficit conditions.

A local-saturation-and-delay MRI method for evaluation of red blood cells aggregation in vivo for tumor-bearing or drug-used rats.

Hyperviscosity syndrome (HVS) is a combination of clinical signs and symptoms related to increased blood viscosity. HVS can increase the thrombotic risk by causing a major disturbance to the blood flow, which is usually found in the advanced stages of the tumor. Moreover, some of the drugs used in chemotherapy, such as 5-fluorouracil and erythropoietin, are also capable of causing HVS through their respective pathways. Clinically, the viscosity of a patient's blood sample is measured by a rotary rheometer to estimate the risk of hyperviscosity syndrome. However, the measurement of blood viscosity in vitro is easily affected by storage time, storage environment, and anticoagulants. In addition, the fluid conditions in the rheometer are quite different from those in natural blood vessels, making this method inappropriate for evaluating blood viscosity and its effects in vivo under physiological condition. Herein, we presented a novel magnetic resonance imaging method called local-saturation-and-delay imaging (LSDI). The radial distributions of flow velocity measured by LSDI are consistent with the Ultrasonic (US) method (Spearman correlation coefficient r = 0.990). But the result of LSDI is more stable than US (p < 0.0001). With the LSDI method, we can directly measure the radial distribution of diastolic flow velocity, and further use these data to calculate the whole blood relative viscosity (WBRV) and erythrocyte aggregation trend. It was a strong correlation between the results measured by LSDI and rotary rheometer in the group of rats given erythropoietin. Furthermore, experimental results in glioma rats indicate that LSDI is equivalent to a rheometer as a method for predicting the risk of hyperviscosity syndrome. Therefore, LSDI, as a non-invasive method, can effectively follow the changes in WBRV in rats and avoid the effect of blood sampling during the experiment on the results. In conclusion, LSDI is expected to become a novel method for real-time in vivo recognition of the cancer progression and the influence of drugs on blood viscosity and RBC aggregation.

In Vivo Nitroreductase Imaging via Fluorescence and Chemical Shift Dependent 19 F NMR.

Nitroreductase (NTR) is an important biomarker widely used to evaluate the degree of tumor hypoxia. Although a few optical methods have been reported for detecting nitroreductase at low concentration ranges, an effective strategy for nitroreductase monitoring in vivo without limits to the imaging depth is still lacking. Herein, a novel dual-mode NIR fluorescence and 19 F MRI agent, FCy7-NO2 , is proposed for imaging tumor hypoxia. We show that FCy7-NO2 serves as not only a rapid NIR fluorescence enhanced probe for monitoring and bioimaging of nitroreductase in tumors, but also a novel 19 F MR chemical shift-sensitive contrast agent for selectively detecting nitroreductase catalyzed reduction. Notably, integrating two complementary imaging technologies into FCy7-NO2 enables sensitive detection of nitroreductase in a broad concentration range without tissue-depth limit. In general, this agent has a remarkable response to nitroreductase, which provides a promising method for understanding tumor evolution and its physiological role in the hypoxic microenvironment.

Antimicrobial activity of CT-K3K7, a modified peptide by lysine substitutions from ctry2459 - A Chaerilus tryznai scorpion venom peptide.

Antimicrobial peptides (AMPs) have started to garner more interest as novel antimicrobial agents. The scorpion venom peptide ctry2459 was modified to CT-K3K7 by lysine substitutions at the 3rd and 7th positions to increase the cationic properties. We discovered that the modified peptides CT-K3K7 had improved antibacterial activity, higher thermal stability, as well as lower hemolytic activity. It can kill S. aureus and P. aeruginosa rapidly, and reduce the production of biofilm and live bacterial residues in biofilm in vitro. CT-K3K7 has also been demonstrated to decrease bacterial counts, abscess area, and inflammatory cell infiltration in the mouse subcutaneous abscess models that were duplicated by S. aureus and P. aeruginosa. CT-K3K7 has difficulty in inducing S. aureus and P. aeruginosa to develop drug resistance, which may be related to the bactericidal properties. CT-K3K7 increases cationic properties by lysine substitutions can increase the electrostatic force between the peptides and the bacterial surface, which can lead to an increase in bacterial membrane permeability and DNA binding. In conclusion, the modified peptide CT-K3K7 enhances the antimicrobial activity and can be a novel antimicrobial agent candidate for the treatment of infections by S. aureus and P. aeruginosa.

Evaluation of Right Ventricular Function and Myocardial Microstructure in Fetal Hypoplastic Left Heart Syndrome.

Right ventricular (RV) function is one of the critical factors affecting the prognosis of fetuses with hypoplastic left heart syndrome (HLHS). Our study objectives included assessment of cardiac function and comprehensive measurement of cardiac microstructure. We retrospectively studied 42 fetuses diagnosed as HLHS by echocardiography. Myocardial deformation of the right ventricular wall was calculated automatically in offline software. Postmortem cardiac imaging for three control fetal hearts and four HLHS specimens was performed by a 9.4T DTI scanner. Myocardial deformation parameters of the RV (including strain, strain rate, and velocity) were significantly lower in HLHS fetuses (all p < 0.01). FA values increased (0.18 ± 0.01 vs. 0.21 ± 0.02; p < 0.01) in HLHS fetuses, but MD reduced (1.3 ± 0.15 vs. 0.88 ± 0.13; p < 0.001). The HLHS fetuses' RV lateral base wall (−7.31 ± 51.91 vs. −6.85 ± 31.34; p = 0.25), middle wall (1.71 ± 50.92 vs. −9.38 ± 28.18; p < 0.001), and apical wall (−6.19 ± 46.61 vs. −11.16 ± 29.86, p < 0.001) had HA gradient ascent but HA gradient descent in the anteroseptal wall (p < 0.001) and inferoseptal wall (p < 0.001). RV basal lateral wall HA degrees were correlated with RVGLS (R2 = 0.97, p = 0.02). MD values were positively correlated with RVGLS (R2 = 0.93, p = 0.04). Our study found morphological and functional changes of the RV in HLHS fetuses, and cardiac function was related to the orientation patterns of myocardial fibers. It may provide insight into understanding the underlying mechanisms of impaired RV performance in HLHS.

Assessment of functional relevance of genes associated with local temperature variables in Arabidopsis thaliana.

How likely genetic variations associated with environment identified in silico from genome wide association study are functionally relevant to environmental adaptation has been largely unexplored experimentally. Here we analyzed top 29 genes containing polymorphisms associated with local temperature variation (minimum, mean, maximum) among 1129 natural accessions of Arabidopsis thaliana. Their loss-of-function mutants were assessed for growth and stress tolerance at five temperatures. Twenty genes were found to affect growth or tolerance at one or more of these temperatures. Significantly, genes associated with maximum temperature more likely have a detect a function at higher temperature, while genes associated with minimum temperature more likely have a function at lower temperature. In addition, gene variants are distributed more frequently at geographic locations where they apparently offer an enhanced growth or tolerance for five genes tested. Furthermore, variations in a large proportion of the in silico identified genes associated with minimum or mean-temperatures exhibited a significant association with growth phenotypes experimentally assessed at low temperature for a small set of natural accessions. This study shows a functional relevance of gene variants associated with environmental variables and supports the feasibility of the use of local temperature factors in investigating the genetic basis of temperature adaptation.

Machine learning-based radiomics for multiple primary prostate cancer biological characteristics prediction with 18F-PSMA-1007 PET: comparison among different volume segmentation thresholds.

BACKGROUND: PET-based radiomics features could predict the biological characteristics of primary prostate cancer (PCa). However, the optimal thresholds to predict the biological characteristics of PCa are unknown. This study aimed to compare the predictive power of 18F-PSMA-1007 PET radiomics features at different thresholds for predicting multiple biological characteristics. METHODS: One hundred and seventy-three PCa patients with complete preoperative 18F-PSMA-1007 PET examination and clinical data before surgery were collected. The prostate lesions' volumes of interest were semi-automatically sketched with thresholds of 30%, 40%, 50%, and 60% maximum standardized uptake value (SUVmax). The radiomics features were respectively extracted. The prediction models of Gleason score (GS), extracapsular extension (ECE), and vascular invasion (VI) were established using the support vector machine. The performance of models from different thresholding regions was assessed using receiver operating characteristic curve and confusion matrix-derived indexes. RESULTS: For predicting GS, the 50% SUVmax model showed the best predictive performance in training (AUC, 0.82 [95%CI 0.74-0.88]) and testing cohorts (AUC, 0.80 [95%CI 0.66-0.90]). For predicting ECE, the 40% SUVmax model exhibit the best predictive performance (AUC, 0.77 [95%CI 0.68-0.84] and 0.77 [95%CI 0.63-0.88]). As for VI, the 50% SUVmax model had the best predictive performance (AUC, 0.74 [95%CI 0.65-0.82] and 0.74 [95%CI 0.56-0.82]). CONCLUSION: The 18F-1007-PSMA PET-based radiomics features at 40-50% SUVmax showed the best predictive performance for multiple PCa biological characteristics evaluation. Compared to the single PSA model, radiomics features may provide additional benefits in predicting the biological characteristics of PCa.

Mutation in Mg-Protoporphyrin IX Monomethyl Ester (Oxidative) Cyclase Gene ZmCRD1 Causes Chlorophyll-Deficiency in Maize.

Chlorophyll molecules are non-covalently associated with chlorophyll-binding proteins to harvest light and perform charge separation vital for energy conservation during photosynthetic electron transfer in photosynthesis for photosynthetic organisms. The present study characterized a pale-green leaf (pgl) maize mutant controlled by a single recessive gene causing chlorophyll reduction throughout the whole life cycle. Through positional mapping and complementation allelic test, Zm00001d008230 (ZmCRD1) with two missense mutations (p.A44T and p.T326M) was identified as the causal gene encoding magnesium-protoporphyrin IX monomethyl ester cyclase (MgPEC). Phylogenetic analysis of ZmCRD1 within and among species revealed that the p.T326M mutation was more likely to be causal. Subcellular localization showed that ZmCRD1 was targeted to chloroplasts. The pgl mutant showed a malformed chloroplast morphology and reduced number of starch grains in bundle sheath cells. The ZmCRD1 gene was mainly expressed in WT and mutant leaves, but the expression was reduced in the mutant. Most of the genes involved in chlorophyll biosynthesis, chlorophyll degradation, chloroplast development and photosynthesis were down-regulated in pgl. The photosynthetic capacity was limited along with developmental retardation and production reduction in pgl. These results confirmed the crucial role of ZmCRD1 in chlorophyll biosynthesis, chloroplast development and photosynthesis in maize.

Protocol for detecting substrates in living cells by targeted molecular probes through hyperpolarized 129Xe MRI.

Due to limited detection sensitivity and contrast limitation, imaging substrates with 129Xe MRI in living cells is still a challenge. Here, we present an effective protocol to detect and image substrates in human lung cancer cells A549 with hyperpolarized 129Xe MRI. This protocol was optimized for a cryptophane-based probe sensitive to biothiols and can be expanded to other Xe-based probes to detect potential biomarkers in other mammalian cells. For complete details on the use and execution of this protocol, please refer to Zeng et al. (2021).

In vitro and in vivo Activity of Phibilin Against Candida albicans.

The increase in the occurrence of antifungal-resistant Candida albicans infections necessitates more research to explore alternative effective and safe agents against this fungus. In this work, Phibilin, a new antimicrobial peptide obtained from Philomycus bilineatus and used in traditional Chinese medicine, effectively inhibits the growth and activities of C. albicans, including the clinical resistant strains. Phibilin is a fungicidal antimicrobial peptide that exhibited its antimicrobial effect against C. albicans mainly by disrupting the membrane and interacting with the DNA of the fungi. In particular, Phibilin induces the necrosis of C. albicans via the ROS-related pathway. Moreover, this antifungal compound inhibited the biofilm formation of C. albicans by preventing the development of hyphae in a dose-dependent manner. Furthermore, Phibilin and clotrimazole displayed a synergistic effect in inhibiting the growth of the fungi. In the mouse cutaneous infection model, Phibilin significantly inhibited the formation of skin abscesses and decreased the counts of C. albicans cells in the infected area. Overall, Phibilin is potentially an effective agent against skin infections caused by C. albicans.

In vitro and in vivo antibacterial activity of a lysine-rich scorpion peptide derivative.

Antimicrobial peptides are widely acknowledged as an alternative class of antimicrobial agents. In this study, a lysine-rich scorpion peptide derivative Pacavin-5K was designed, which showed an improved antibacterial spectrum, significantly higher antibacterial activity, and lower toxicity compared to the native peptide. It also showed an improved thermal and serum stability. Notably, Pacavin-5K significantly decreased the bacterial counts in the wounded region in the mouse cutaneous infection model caused by Staphylococcus aureus and Pseudomonas aeruginosa. Moreover, Pacavin-5K did not induce bacterial resistance associated with its antibacterial mechanism disrupting the membrane. Furthermore, Pacavin-5K could kill the S. aureus cells at the biofilm state. Overall, Pacavin-5K could be a potential alternative antibacterial agent against skin infection caused by S. aureus and P. aeruginosa.

Ultrasensitive molecular building block for biothiol NMR detection at picomolar concentrations.

Magnetic resonance imaging (MRI) provides structural and functional information, but it did not probe chemistry. Chemical information could help improve specificity of detection. Herein, we introduce a general method based on a modular design to construct a molecular building block Xe probe to help image intracellular biothiols (glutathione (GSH), cysteine (Cys) and homocysteine (Hcy)), the abnormal content of which is related to various diseases. This molecular building block possesses a high signal-to-noise ratio and no background signal effects. Its detection threshold was 100 pM, which enabled detection of intracellular biothiols in live cells. The construction strategy can be easily extended to the detection of any other biomolecule or biomarker. This modular design strategy promotes efficiency of development of low-cost multifunctional probes that can be combined with other readout parameters, such as optical readouts, to complement 129Xe MRI to usher in new capabilities for molecular imaging.

Comparative transcription analysis of resistant mutants against four different antibiotics in Pseudomonas aeruginosa.

The emergence of antibiotic resistance has severely impaired the treatment of infections caused by Pseudomonas aeruginosa. There are few studies related to comparing the antibiotics resistance mechanisms of P. aeruginosa against different antibiotics. In this study, RNA sequencing was used to investigate the differences of transcriptome between wild strain and four antibiotics resistant strains of P. aeruginosa PAO1 (polymyxin B, ciprofloxacin, doxycycline, and ceftriaxone). Compared to the wild strain, 1907, 495, 2402, and 116 differentially expressed genes (DEGs) were identified in polymyxin B, ciprofloxacin, doxycycline, and ceftriaxone resistant PAO1, respectively. After analysis of genes related to antimicrobial resistance, we found genes implicated in biofilm formation (pelB, pelC, pelD, pelE, pelF, pelG, algA, algF, and alg44) were significantly upregulated in polymyxin B-resistant PAO1, efflux pump genes (mexA, mexB, oprM) and biofilm formation genes (pslJ, pslK and pslN) were upregulated in ciprofloxacin-resistant PAO1; other efflux pump genes (mexC, mexD, oprJ) were upregulated in doxycycline-resistant PAO1; ampC were upregulated in ceftriaxone-resistant PAO1. As a consequence of antibiotic resistance, genes related to virulence factors such as type Ⅱ secretion system (lasA, lasB and piv) were significantly upregulated in polymyxin B-resistant PAO1, and type Ⅲ secretion system (exoS, exoT, exoY, exsA, exsB, exsC, exsD, pcrV, popB, popD, pscC, pscE, pscG, and pscJ) were upregulated in doxycycline-resistant PAO1. While, ampC were upregulated in ceftriaxone-resistant PAO1. In addition, variants were obtained in wild type and four antibiotics resistant PAO1. Our findings provide a comparative transcriptome analysis of antibiotic resistant mutants selected by different antibiotics, and might assist in identifying potential therapeutic strategies for P. aeruginosa infection.