Compensation of small data with large filters for accurate liver vessel segmentation from contrast-enhanced CT images.

BACKGROUND: Segmenting liver vessels from contrast-enhanced computed tomography images is essential for diagnosing liver diseases, planning surgeries and delivering radiotherapy. Nevertheless, identifying vessels is a challenging task due to the tiny cross-sectional areas occupied by vessels, which has posed great challenges for vessel segmentation, such as limited features to be learned and difficult to construct high-quality as well as large-volume data. METHODS: We present an approach that only requires a few labeled vessels but delivers significantly improved results. Our model starts with vessel enhancement by fading out liver intensity and generates candidate vessels by a classifier fed with a large number of image filters. Afterwards, the initial segmentation is refined using Markov random fields. RESULTS: In experiments on the well-known dataset 3D-IRCADb, the averaged Dice coefficient is lifted to 0.63, and the mean sensitivity is increased to 0.71. These results are significantly better than those obtained from existing machine-learning approaches and comparable to those generated from deep-learning models. CONCLUSION: Sophisticated integration of a large number of filters is able to pinpoint effective features from liver images that are sufficient to distinguish vessels from other liver tissues under a scarcity of large-volume labeled data. The study can shed light on medical image segmentation, especially for those without sufficient data.

Comprehensive pan-cancer analysis unveils the significant prognostic value and potential role in immune microenvironment modulation of TRIB3.

TRIB3, a pseudokinase, was previously studied within only some specific cancer types, leaving its comprehensive functions in pan-cancer contexts largely unexplored. Here, we performed an integrated analysis of TRIB3 expression, prognosis, genetic alterations, functional enrichment and tumor immune-related characteristics in 33 cancer types. Our results showed that TRIB3 exhibits high expression levels across 24 different cancer types and correlates closely with unfavorable prognoses. Meanwhile, TRIB3 shows mutations in a wide spectrum of 22 distinct cancer types, with the predominant mutation types being missense mutations and gene amplifications, and significant changes in DNA methylation levels in 14 types of cancer. We further discovered that TRIB3 expression is significantly associated with cancer immune-related genome mutations, such as tumor mutational burden (TMB), microsatellite instability (MSI) and DNA mismatch repair (MMR), and infiltration of immunosuppressive cells, such as CD4+ Th2 cells and myeloid-derived suppressor cells (MDSCs), into the tumor microenvironment. These results indicated that the expression of TRIB3 might reshape the tumor immune microenvironment (TIME) and lead to immunosuppressive "cold" tumors. In addition, our results confirmed that the loss of function of TRIB3 inhibits cell proliferation, promotes apoptosis, and leads to significant enrichment of "hot" tumor-related immune pathways, at least in breast cancer cells, which further supports the important role of TRIB3 in cancer prognosis and TIME regulation. Together, this pan-cancer investigation provided a comprehensive understanding of the critical role of TRIB3 in human cancers, and suggested that TRIB3 might be a promising prognostic biomarker and a potential target for cancer immunotherapy.

The signaling pathways and targets of natural products from traditional Chinese medicine treating gastric cancer provide new candidate therapeutic strategies.

Gastric cancer (GC) is one of the severe malignancies with high incidence and mortality, especially in Eastern Asian countries. Significant advancements have been made in diagnosing and treating GC over the past few decades, resulting in tremendous improvements in patient survival. In recent years, traditional Chinese medicine (TCM) has garnered considerable attention as an alternative therapeutic approach for GC due to its multicomponent and multitarget characteristics. Consequently, natural products found in TCM have attracted researchers' attention, as growing evidence suggests that these natural products can impede GC progression by regulating various biological processes. Nevertheless, their molecular mechanisms are not systematically uncovered. Here, we review the major signaling pathways involved in GC development. Additionally, clinical GC samples were analyzed. Moreover, the anti-GC effects of natural products, their underlying mechanisms and potential targets were summarized. These summaries are intended to facilitate further relevant research, and accelerate the clinical applications of natural products in GC treatment.

Proliferatins suppress lipopolysaccharide-induced inflammation via inhibition of the NF-κB and MAPK signaling pathways.

Three previously undescribed polyketides [proliferatin A-C (1-3)] with anti-inflammatory activity were isolated from Fusarium proliferatum. 1-3 attenuated the production of inflammatory signal messengers including nitric oxide (NO), reactive oxygen species, proinflammatory cytokines interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß), as well as the related proteins nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-induced RAW264.7 macrophages. Transcriptome analyses based on RNA-seq indicated the potential anti-inflammatory mechanism of 1-3 involved in the nuclear factor kappa-B (NF-κB) and mitogen activated protein kinases (MAPKs) signaling pathways. Experimental evaluation of the protein levels revealed that 1-3 can inhibit the phosphorylation of IκB kinase (IKK), the degradation of NF-κB Inhibitor-α (IκBα), the phosphorylation of nuclear factor-κB (NF-κB) and can reduce NF-κB transportation to the nucleus. Interestingly, 1-3 decreased the phosphorylation of MAPKs including p-p38, p-ERK, and p-JNK. Molecular docking models suggest that binding of 1-3 to TLR4-MD-2 complex may lead to inhibition of NF-κB and MAPK signaling pathways, which was confirmed in vitro by surface plasmon resonance (SPR) assays. 1-3 can thus constitute potential therapeutic candidates for the treatment of inflammation-associated diseases.

Investigation of the Anti-Inflammatory Activity of Fusaproliferin Analogues Guided by Transcriptome Analysis.

Background: Excessive inflammation results in severe tissue damage as well as serious acute or chronic disorders, and extensive research has focused on finding new anti-inflammatory hit compounds with safety and efficacy profiles from natural products. As promising therapeutic entities for the treatment of inflammation-related diseases, fusaproliferin and its analogs have attracted great interest. However, the underlying anti-inflammatory mechanism is still poorly understood and deserves to be further investigated. Methods: For the estimation of the anti-inflammatory activity of fusaproliferin (1) and its analogs (2-4) in vitro and in vivo, lipopolysaccharide (LPS)-induced RAW264.7 macrophages and zebrafish embryos were employed. Then, transcriptome analysis was applied to guide subsequent western blot analysis of critical proteins in related signaling pathways. Surface plasmon resonance assays (SPR) combined with molecular docking analyses were finally applied to evaluate the affinity interactions between 1-4 and TLR4 and provide a possible interpretation of the downregulation of related signaling pathways. Results: 1-4 significantly attenuated the production of inflammatory messengers, including nitric oxide (NO), reactive oxygen species (ROS), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß), as well as nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), in LPS-induced RAW264.7 macrophages. Transcriptome analyses based on RNA-seq indicated the ability of compound 1 to reverse LPS stimulation and the nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPKs) signaling pathways contribute to the anti-inflammatory process. Experimental verification at the protein level revealed that 1 can inhibit the activation of inhibitor of NF-κB kinase (IKK), degradation of inhibitor of NF-κB (IκB), and phosphorylation of NF-κB and reduce nuclear translocation of NF-κB. 1 also decreased the phosphorylation of MAPKs, including p38, extracellular regulated protein kinases (ERK), and c-Jun N-terminal kinase (JNK). SPR assays and molecular docking results indicated that 1-4 exhibited affinity for the TLR4 protein with KD values of 23.5-29.3 µM. Conclusion: Fusaproliferin and its analogs can be hit compounds for the treatment of inflammation-associated diseases.

Aureonitol Analogues and Orsellinic Acid Esters Isolated from Chaetomium elatum and Their Antineuroinflammatory Activity.

Overexpression of various pro-inflammatory factors in microglial cells tends to induce neurodegenerative diseases, for which there is no effective therapy available. Aureonitol (1) and seven analogues, including six previously undescribed [elatumenol A-F (2-4, 6-8, respectively)], along with two new orsellinic acid esters [elatumone A and B (9 and 10)], were isolated from Chaetomium elatum. The structures of the compounds were established through comprehensive analysis of spectroscopic data, including high-resolution mass spectra and one- and two-dimensional NMR, and absolute configurations determined by the Mosher method, dimolybdenum tetraacetate-induced circular dichroism, and theoretical calculations including electronic circular dichroism and NMR. Metabolites 3, 4, 7, and 8 exhibited antineuroinflammatory activity by attenuating the production of inflammatory mediators, such as nitric oxide, interleukin-6, interleukin-1ß, tumor necrosis factor-α, and reactive oxygen species. Western blot results indicated 8 decreases the level of inducible nitric oxide synthase and cyclooxygenase-2 and suppresses the expression of Toll-like receptor 4 and nuclear factor kappa-B (NF-κB) as well as the phosphorylation of the inhibitor of NF-κB and p38 mitogen-activated protein kinases in lipopolysaccharide-activated BV-2 microglial cells.

Determination of fluorine content in rocks using laser-induced breakdown spectroscopy assisted with radical synthesis.

In the atmosphere, fluorine element in rocks is hard to detect using fluorine atomic emission spectrum in laser-induced breakdown spectroscopy. In this study, a novel radical synthesis method based on laser ablation was proposed, by which strontium-fluorine (SrF) radical spectrum was collected to quantify fluorine element in rocks instead of fluorine atom spectrum. A pure strontium carbonate was placed orthogonally to the sample, and ablated by an additional laser to provide sufficient strontium atoms for promoting SrF radical formation. The fluorine content in rocks was sensitively and accurately determined by SrF radical emission signal. The coefficient of determination, average relative standard deviation, root mean square error, limit of detection, and limit of qualification were 0.996, 4.68%, 0.0068 wt%, 6.36 µg g-1, and 21.2 µg g-1, respectively. This work proved that this novel method provides a new way to promote radical synthesis and has considerable potential for detecting fluorine in rocks in geological exploration.

Sensitive analysis of fluorine and chlorine elements in water solution using laser-induced breakdown spectroscopy assisted with molecular synthesis.

Fluorine and chlorine are key elements to affecting water quality, but they are hard to be determined by conventional laser-induced breakdown spectroscopy (LIBS). To achieve high sensitivity detection of them, the CaF and CaCl molecules were synthesized by combining calcium in calcite and F and Cl in sample. The temporal characteristics of CaF and CaCl molecular emissions were investigated. It shows that molecular emission of CaF and CaCl has a longer lifetime and high spectral intensity than that of their atomic emissions. Such unique feature of molecular emission inspired us to use it for high sensitivity analysis of Cl and F elements in water. The results show that these two elements can be sensitively and accurately detected using LIBS assisted with molecular emission. The limits of detections (LoDs) were 0.38 mg/L and 1.03 mg/L for F and Cl elements, respectively, and the limit of quantitation (LoQ) was 3.404 mg/L to 20.569 mg/L for fluorine elements and 9.986 mg/L to 39.757 mg/L for fluorine. These detection limits can meet the World Health Organization's detection requirements for F and Cl elements in water. The results show that LIBS assisted with molecular synthesis has a huge potential in water quality monitoring.

Lead of detection in rhododendron leaves using laser-induced breakdown spectroscopy assisted by laser-induced fluorescence.

Laser-induced breakdown spectroscopy assisted by laser-induced fluorescence (LIBS-LIF) was applied to determine lead (Pb) in rhododendron leaves. Rhododendron leaves are essential types of herbal materials. Rapid detection of lead in rhododendron leaves is urgent for drug monitoring. In this paper, the powder method and solid-liquid-solid transformation (SLST) method were employed as sample preparation. The results showed that the signal of the Pb I 405.78 nm line was substantially enhanced. For samples A, B and C, the LoD values of 0.054 mg/kg, 0.059 mg/kg, 0.062 mg/kg were achieved with R2 values of 0.997, 0.996, 0.997 via the SLST approach, whose sensitivity and accuracy was slightly higher compared to the powder method. The RMSECV values of both methods were minimal, ranging from 0.538 to 2.117 mg/kg. Lead content detected by LIBS-LIF in the three samples was between 1.5 and 2.8 mg/kg. The results of lead were validated by inductively coupled plasma optical emission spectrometry (ICP-OES). This research provided us with new technology for the rapid and accurate determination of Pb element in rhododendron leaves.

Sulfur determination in laser-induced breakdown spectroscopy combined with resonance Raman scattering.

Sulfur is an essential element in industry, but it is difficult to be detected by laser-induced breakdown spectroscopy (LIBS). In this work, the disulfide radical Raman scattering was observed in sulfur plasma by combining LIBS with resonance Raman scattering (LIBS-RRS). Sulfur has been ablated by a focused laser beam to generate plasma, in which some sulfur atoms were combined to form disulfide radicals. The disulfide radical resonance Raman was excited by a 306.4 nm wavelength laser and observed at 710 and 1420 cm-1 Raman shift. Using different contents of sulfur mixed with alumina (Al2O3) powder, both LIBS and LIBS-RRS calibrations were obtained at the same ablation laser energy. The calibration curve of sulfur atomic emission S I 921.28 nm was set up, and the linear coefficient (R2) was 0.285 and the detection limit (LoD) was 13.092 wt %. While the R2 was 0.966 and LoD was 0.118 wt % for S2 710 cm-1 in LIBS-RRS. The results indicate that disulfide radical Raman scattering by LIBS-RRS is promising for the determination of sulfur content and the diagnosis of molecular evolution in plasma.

A label-free ultrasensitive fluorescence detection of viable Salmonella enteritidis using enzyme-induced cascade two-stage toehold strand-displacement-driven assembly of G-quadruplex DNA.

The harm of Salmonella enteritidis (S. enteritidis ) to public health mainly by contaminating fresh food and water emphasizes the urgent need for rapid detection techniques to help control the spread of the pathogen. In this assay, an newly designed capture probe complex that contained specific S. enteritidis-aptamer and hybridized signal target sequence was used for viable S. enteritidis recognition directly. In the presence of the target S. enteritidis, single-stranded target sequences were liberated and initiated the replication-cleavage reaction, producing numerous G-quadruplex structures with a linker on the 3'-end. And then, the sensing system took innovative advantage of quadratic linker-induced strand-displacement for the first time to release target sequence in succession, leading to the cyclic reuse of the target sequences and cascade signal amplification, thereby achieving the successive production of G-quadruplex structures. The fluorescent dye, N-Methyl mesoporphyrin IX, binded to these G-quadruplex structures and generated significantly enhanced fluorescent signals to achieve highly sensitive detection of S. enteritidis down to 60 CFU/mL with a linear range from 10(2) to 10(7)CFU/mL. By coupling the cascade two-stage target sequences-recyclable toehold strand-displacement with aptamer-based target recognition successfully, it is the first report on a novel non-label, modification-free and DNA extraction-free ultrasensitive fluorescence biosensor for detecting viable S. enteritidis directly, which can discriminate from dead S. enteritidis.

Investigation on host susceptibility of Tibetan pig to infection of porcine reproductive and respiratory syndrome virus through viral challenge study.

Previous reports showed that infection of porcine reproductive and respiratory syndrome virus (PRRSV) stimulated a variable host response and pig susceptibility to PRRSV was largely dependent on its genetic composition. In the present study, host susceptibility of Tibetan pig to PRRSV was compared with other two pig breeds, ZangMei black and Large White, by challenge of them with highly pathogenic PRRSV (HP-PRRSV). In the first challenge test, each eight piglets of the three breeds were inoculated with HP-PRRSV and clinical symptoms, viremia and animal mortality were examined up to 28 days post inoculation (DPI). In the secondary pathological study, each twelve piglets of the three breeds were challenged and three pigs of each breed were sacrificed on 4, 7, and 14 DPI for examination of gross damage and lung microscopic lesions. The results showed that no typical clinical signs such as cough, diarrhea and high fever were observed in challenged Tibetan pigs, which however all occurred in Large White accompanied with ∼40% mortality (3/8). In addition, a significant low and short viremia was detected specifically in Tibetan pigs. Based on histopathological analysis of lung sections, a mild to moderate interstitial pneumonia in Tibetan pigs and a much severe pneumonia in Large White were identified on 7-14 DPI. In summary, the study demonstrated that three genetically different pig breeds exhibited a differential host susceptibility to HP-PRRSV and Tibetan pig was much less susceptible to the virus in the three tested pig breeds.

Characteristics of Plasmids Coharboring 16S rRNA Methylases, CTX-M, and Virulence Factors in Escherichia coli and Klebsiella pneumoniae Isolates from Chickens in China.

The objective of this study was to characterize plasmids coharboring 16S rRNA methylases, blaCTX-M and virulence-associated genes in Escherichia coli and Klebsiella pneumoniae isolates from chickens in China. A total of 32 positive transconjugants exhibited coresistance to amikacin and cefotaxime in E. coli (24/281) and K. pneumoniae (8/93), and were identified by conjugation experiments and S1-pulsed-field gel electrophoresis. Polymerase chain reaction amplification assay detecting resistance genes showed that rmtB or armA gene accompanied with different blaCTX-M genes coexisted on 32 transferred plasmids. The blaCTX-M-98b gene was identified in chicken-derived E. coli and K. pneumoniae for the first time. The association between resistance genes and virulence genes was observed in the transferred plasmids; 68.8% (22/32) transferred resistance plasmids coharboring various virulence genes including traT, iutA, fyuA, msbB, and vagC genes with diverse proportions. Genetic stability tests revealed that 93.8% (30/32) transferred plasmids continued to exist in the host strain after continuous passage of 30 times in 15 days. Furthermore, 87.5% (28/32) conjugants showed no significant differences in growth rates compared with E. coli J53. Results of the growth competition assay showed that conjugants have low fitness cost, which indicated that there were no obvious negative effects on the host's growth. The combination of blaCTX-M-98b-rmtB-traT on 85-kb transferred IncF plasmids in E. coli, and blaCTX-M-14-rmtB-traT on 95-kb transferred IncF plasmids in K. pneumoniae were first identified in this study. These features of plasmids may contribute to the successful spread of resistance and virulence among pathogens of different sources and geographical origins.

First report of macrolide resistance gene erm(T) harbored by a novel small plasmid from Erysipelothrix rhusiopathiae.

The macrolide resistance gene erm(T) was identified for the first time in a porcine Erysipelothrix rhusiopathiae isolate from swine in China. The novel 3,749-bp small plasmid pER29, which carries erm(T), had a G+C content of 31% and four distinct open reading frames. The presence of pER29 increased by at least 128-fold the MICs of clindamycin and erythromycin for E. rhusiopathiae. The fitness cost of pER29 could be responsible for the low frequency of erm(T) in E. rhusiopathiae.

[Extraction and purification of the Klebsiella pneumoniae capsular polysaccharide and the effection on the cell immunoactivity].

Klebsiella pneumoniae was cultured followed by the preparation and immunoactivity elucidating of its polysaccharide (CPS). The lysis of cell is the first key step in the preparation, under the co-action of trypsin, lysozyme and NP-40, the cell lysed within 2h, then the lysate was concentrated by ultrafiltration which serves as concentrating and partial purifying action simultaneously. Crude CPS was got by ethanol precipitation, then purified through the Ion-exchange and gel filtration, the purity of CPS was judged by the gel filtration and agarose gel electrophoresis. The effect of CPS on the cell immunoactivity was studied in detail, the results show that CPS possesses bidirectional immunoregulation on the spleen cells of mice, that is, low concentration of CPS can stimulate the immune response while the high concentration manifests the inhibition significantly. The investigation results will benefit on the exploitation of the CPS.