Spatial proximity and gene function: a new dimension in prokaryotic gene association network analysis with 3D-GeneNet.

Understanding the biological functions and processes of genes, particularly those not yet characterized, is crucial for advancing molecular biology and identifying therapeutic targets. The hypothesis guiding this study is that the 3D proximity of genes correlates with their functional interactions and relevance in prokaryotes. We introduced 3D-GeneNet, an innovative software tool that utilizes high-throughput sequencing data from chromosome conformation capture techniques and integrates topological metrics to construct gene association networks. Through a series of comparative analyses focused on spatial versus linear distances, we explored various dimensions such as topological structure, functional enrichment levels, distribution patterns of linear distances among gene pairs, and the area under the receiver operating characteristic curve by utilizing model organism Escherichia coli K-12. Furthermore, 3D-GeneNet was shown to maintain good accuracy compared to multiple algorithms (neighbourhood, co-occurrence, coexpression, and fusion) across multiple bacteria, including E. coli, Brucella abortus, and Vibrio cholerae. In addition, the accuracy of 3D-GeneNet's prediction of long-distance gene interactions was identified by bacterial two-hybrid assays on E. coli K-12 MG1655, where 3D-GeneNet not only increased the accuracy of linear genomic distance tripled but also achieved 60% accuracy by running alone. Finally, it can be concluded that the applicability of 3D-GeneNet will extend to various bacterial forms, including Gram-negative, Gram-positive, single-, and multi-chromosomal bacteria through Hi-C sequencing and analysis. Such findings highlight the broad applicability and significant promise of this method in the realm of gene association network. 3D-GeneNet is freely accessible at https://github.com/gaoyuanccc/3D-GeneNet.

Dysfunctional circadian clock accelerates cancer metastasis by intestinal microbiota triggering accumulation of myeloid-derived suppressor cells.

Circadian homeostasis in mammals is a key intrinsic mechanism for responding to the external environment. However, the interplay between circadian rhythms and the tumor microenvironment (TME) and its influence on metastasis are still unclear. Here, in patients with colorectal cancer (CRC), disturbances of circadian rhythm and the accumulation of monocytes and granulocytes were closely related to metastasis. Moreover, dysregulation of circadian rhythm promoted lung metastasis of CRC by inducing the accumulation of myeloid-derived suppressor cells (MDSCs) and dysfunctional CD8+ T cells in the lungs of mice. Also, gut microbiota and its derived metabolite taurocholic acid (TCA) contributed to lung metastasis of CRC by triggering the accumulation of MDSCs in mice. Mechanistically, TCA promoted glycolysis of MDSCs epigenetically by enhancing mono-methylation of H3K4 of target genes and inhibited CHIP-mediated ubiquitination of PDL1. Our study links the biological clock with MDSCs in the TME through gut microbiota/metabolites in controlling the metastatic spread of CRC, uncovering a systemic mechanism for cancer metastasis.

Bases-dependent Rapid Phylogenetic Clustering (Bd-RPC) enables precise and efficient phylogenetic estimation in viruses.

Understanding phylogenetic relationships among species is essential for many biological studies, which call for an accurate phylogenetic tree to understand major evolutionary transitions. The phylogenetic analyses present a major challenge in estimation accuracy and computational efficiency, especially recently facing a wave of severe emerging infectious disease outbreaks. Here, we introduced a novel, efficient framework called Bases-dependent Rapid Phylogenetic Clustering (Bd-RPC) for new sample placement for viruses. In this study, a brand-new recoding method called Frequency Vector Recoding was implemented to approximate the phylogenetic distance, and the Phylogenetic Simulated Annealing Search algorithm was developed to match the recoded distance matrix with the phylogenetic tree. Meanwhile, the indel (insertion/deletion) was heuristically introduced to foreign sequence recognition for the first time. Here, we compared the Bd-RPC with the recent placement software (PAGAN2, EPA-ng, TreeBeST) and evaluated it in Alphacoronavirus, Alphaherpesvirinae, and Betacoronavirus by using Split and Robinson-Foulds distances. The comparisons showed that Bd-RPC maintained the highest precision with great efficiency, demonstrating good performance in new sample placement on all three virus genera. Finally, a user-friendly website (http://www.bd-rpc.xyz) is available for users to classify new samples instantly and facilitate exploration of the phylogenetic research in viruses, and the Bd-RPC is available on GitHub (http://github.com/Bin-Ma/bd-rpc).

EPANet-KD: Efficient progressive attention network for fine-grained provincial village classification via knowledge distillation.

OBJECTIVE: Fine-grained classification of historical traditional villages plays a crucial role in guiding the future development and construction of urban and rural areas. This study aims to propose a new dataset for fine-grained classification of traditional villages and to propose an efficient progressive attention network for the problem of low accuracy and efficiency of fine-grained traditional historical village classification. METHODS AND RESULTS: Firstly, in order to further study the long-standing problem of fine-grained classification of traditional villages, a new fine-grained classification dataset of traditional villages containing 4,400 images, referred to as PVCD, is proposed by crawling and hand-arranging. Secondly, a new Progressive Attention Module, abbreviated as PAM, is also proposed. PAM engages in attentional modeling of prominent spatial features within the spatial dimension, subsequently applying attentional modeling to channel features beneath the identified salient spatial features. This process involves salient spatial feature attention modeling of prominent channel features within the dimension to extract discriminative information for fine-grained classification, thereby enhancing the performance of classifying traditional villages with precision. Finally, a new knowledge distillation strategy of softened alignment distillation, or SAD for short, is proposed, which simply and efficiently transfers the knowledge of softened category probability distributions through. Notably, based on the above proposed PAM, the lightweight EPANet-Student and the heavyweight EPANet-Teacher are proposed. In addition, the heavyweight EPANet-Teacher transfers the knowledge of fine-grained categorization of traditional villages to the lightweight EPANet-Student through the proposed SAD, abbreviated as EPANet-KD. The experimental results show that the proposed EPANet-Teacher achieves state-of-the-art performance with an accuracy of 67.27%, and the proposed EPANet-KD achieves comparable performance to the proposed EPANet-Teacher with 3.32M parameters and 0.42G computation. CONCLUSION: The proposed EPANet-KD maintains a good balance of accuracy and efficiency in the fine-grained classification of traditional villages, considerably promoting the research on the fine-grained classification of traditional villages. In addition, it facilitates the digital preservation and development of traditional villages. All datasets, codes and benchmarking results are publicly available for the promotion of this research area. https://github.com/Jack13026212687/EPANet-KD.

Targeting Erbin-mitochondria axis in platelets/megakaryocytes promotes B cell-mediated antitumor immunity.

The roles of platelets/megakaryocytes (MKs), the key components in the blood system, in the tumor microenvironment and antitumor immunity are unclear. In patients with colorectal cancer, the number of platelets was significantly increased in patients with metastasis, and Erbin expression was highly expressed in platelets from patients with metastases. Moreover, Erbin knockout in platelets/MKs suppressed lung metastasis in mice and promoted aggregations of platelets. Mechanistically, Erbin-deficient platelets have increasing mitochondrial oxidative phosphorylation and secrete lipid metabolites like acyl-carnitine (Acar) by abolishing interaction with prothrombotic protein ESAM. Notably, Acar enhanced the activity of mitochondrial electron transport chain complex and mitochondrial oxidative phosphorylation in B cells by acetylation of H3K27 epigenetically. Targeting Erbin in platelets/MKs by a nanovesicle system dramatically attenuated lung metastasis in mice in vivo. Our study identifies an Erbin-mitochondria axis in platelets/MKs, which suppresses B cell-mediated antitumor immunity, suggesting a new way for the treatment of metastasis.

Leaf phenotypic variation and its response to environmental factors in natural populations of Eucommia ulmoides.

BACKGROUND: Eucommia ulmoides leaves have high medicinal and economic value as a dual-purpose substance for medicine and food. Employing leaves from 13 natural populations of Eucommia ulmoides as research objects, this study reveals the variation patterns of intra-specific and inter-specific trait variation and explores the response of leaf characteristics to geographical and climatic changes, aiming to provide a scientific basis for the efficient utilization of leaf resources and the breeding of superior varieties. RESULTS: Descriptive statistical analysis and nested analysis of variance showed significant differences in 11 leaf traits of Eucommia ulmoides inter-populations and intra-populations, with an average coefficient of variation of 17.45%. The coefficient of variation for average leaf phenotypic traits is 20.77%, and the leaf phenotypic variation is mainly from the variation intra-populations. Principal component analysis reveals that the cumulative contribution rate of the top three principal components which mainly contributed to the phenotypic variation of Eucommia ulmoides leaves reached 74.98%, which could be sorted into size traits (34.57%), color traits (25.82%) and shape traits (14.58%). In addition, correlation analysis expresses there is a specific co-variation pattern among leaf traits, with a strong connection between shape, size, and color traits. Geographic and climatic distances are significantly correlated, and mantel test and correlation analysis indicate that leaf traits of Eucommia ulmoides are mainly influenced by altitude. With the increase of altitude, the leaves become smaller. Partial correlation analysis shows that after controlling climate factors, the correlation between some characters and geographical factors disappears significantly. Temperature and precipitation have a great influence on the variation of leaf phenotypic traits, and the larger the leaves are in areas with high temperature and heavy rainfall. CONCLUSIONS: These findings contribute to a further understanding of the leaf morphological characteristics of Eucommia ulmoides and the extent to which the environment influences leaf trait variation. They can provide a scientific basis for the protection and application of Eucommia ulmoides leaf resources in the future.

Covalently Functionalized MoS2 Initiated Gelation of Hydrogels for Flexible Strain Sensing.

Transition metal dichalcogenides (TMDs), with superior mechanical and electrical conductivity, are one of the most promising two-dimensional materials for creating a generation of intelligent and flexible electronic devices. However, due to the high van der Waals and electrostatic attraction, TMD nanomaterials tend to aggregate in dispersants to achieve a stable state, thus severely limiting their further applications. Surface chemical modification is a common strategy for improving the dispersity of TMD nanomaterials; however, there are still constraints such as limited functionalization methods, low grafting rate, and difficult practice application. Thus, it is challenging to develop innovative surface modification systems. Herein, we covalently modify an olefin molecule on surface-inert MoS2, and the modified MoS2 can be used as not only a catalyst for hydrogel polymerization, but also a cross-linker in the hydrogel network. Specifically, allyl is covalently grafted onto chemically exfoliated MoS2, and this modified MoS2 can be uniformly dispersed in polar solvents (such as acetone, N,N-dimethylformamide, and ethanol), remaining stable for more than 2 weeks. The allyl-modified MoS2 can catalyze the polymerization of polyacrylamide hydrogel and then integrate in the network, which increases the tensile strength of the composite hydrogel. The flexible sensor based on the composite hydrogel exhibits an ideal operating range of 600% and a quick response time of 150 ms. At the same time, the flexible device can also track the massive axial stretching movements of human joints, making it a reliable option for the next wave of wearable sensing technology.

PPNet: Identifying Functional Association Networks by Phylogenetic Profiling of Prokaryotic Genomes.

Identification of microbial functional association networks allows interpretation of biological phenomena and a greater understanding of the molecular basis of pathogenicity and also underpins the formulation of control measures. Here, we describe PPNet, a tool that uses genome information and analysis of phylogenetic profiles with binary similarity and distance measures to derive large-scale bacterial gene association networks of a single species. As an exemplar, we have derived a functional association network in the pig pathogen Streptococcus suis using 81 binary similarity and dissimilarity measures which demonstrates excellent performance based on the area under the receiver operating characteristic (AUROC), the area under the precision-recall (AUPR), and a derived overall scoring method. Selected network associations were validated experimentally by using bacterial two-hybrid experiments. We conclude that PPNet, a publicly available (https://github.com/liyangjie/PPNet), can be used to construct microbial association networks from easily acquired genome-scale data. IMPORTANCE This study developed PPNet, the first tool that can be used to infer large-scale bacterial functional association networks of a single species. PPNet includes a method for assigning the uniqueness of a bacterial strain using the average nucleotide identity and the average nucleotide coverage. PPNet collected 81 binary similarity and distance measures for phylogenetic profiling and then evaluated and divided them into four groups. PPNet can effectively capture gene networks that are functionally related to phenotype from publicly prokaryotic genomes, as well as provide valuable results for downstream analysis and experiment testing.

Effect of thymopentin combined with levofloxacin for retreatment smear positive pulmonary tuberculosis / 中国热带医学

@#Abstract: Objective　To analyze the effect of adjuvant to levofloxacin in the treatment of retreatment smear positive pulmonary tuberculosis, as well as its effect on respiratory function, immune function and inflammatory factors. Methods　One hundred cases of retreatment smear positive pulmonary tuberculosis patients admitted to Rudong County People's Hospital in Nantong city in Jiangsu province from 2017 to 2021 were randomly divided into a control group (n=50) and an observation group (n=50) according to random number table method. Both groups received conventional treatment (3 months of isoniazid, rifampicin, ethambutol, pyrazinamide / 6 months of isoniazid, rifampicin, ethambutol), with levofloxacin added to the control group, and thymopentin added to the observation group for the first three months in addition to routine treatment. The treatment effect of the two groups were compared. Results　The sputum smear conversion rate of the observation group was significantly higher than that of the control group after 3 months and 5 months of treatment (χ2=7.142, P<0.05; χ2=6.250, P<0.05). The cavity absorption time and lesion absorption time in the observation group were significantly lower than those in the control group (t=4.006, P<0.05; t=5.165, P<0.05). The turning time of bacteriological culture in the observation group was significantly lower than that in the control group (t=4.220,P<0.05). After 3 months of treatment, CD4+, CD3+, CD4+/CD8+ of the observation group were higher than those of the control group, the differences were statistically significant (t=8.885, P<0.05; t=6.274, P<0.05; t=4.357, P<0.05). After 3 months of treatment, the IFN-γ (interferon-γ) of the observation group was higher than that of the control group (t=8.892, P<0.05), whereas the , IL-10 (interleukin-10) was significantly lower than that in the control group (t=5.986, P<0.05). After 3 months of treatment, forced vital capacity (FVC), forced expiratory volume in one second (forced expiratory volume in one second, FEV 1) and the one-second rate (forced expiratory volume in one second / forced vital capacity, FEV1/FVC) in the observation group were significantly higher than those in the control group (t=11.223, P<0.05; t=10.128, P<0.05; t=4.464, P<0.05). There was no statistically significant difference in the incidence of adverse reactions between the two groups (χ2=0.378, P>0.05). Conclusions　Thymopentin combined with levofloxacin had a significant application effect in the treatment of retreatment smear positive pulmonary tuberculosis, s, which led to improved inflammatory reaction, respiratory function and immune function. Additionally, it can increase sputum smear conversion rate and accelerate patient recovery, improving overall treatment efficacy, with a relatively high clinical application value.

Determination of Pb2+ by Colorimetric Method Based on Catalytic Amplification of Ag Nanoparticles Supported by Covalent Organic Frameworks.

In this paper, covalent organic frameworks (COFs) are prepared by solvothermal synthesis using 1,3,5-benzenetricarboxaldehyde and benzidine as ligands. Then, using COFs as a template, AgCOFs with high catalytic activity is prepared by in situ loading silver nanoparticles (AgNC) on the surface of COFs by sodium borohydride reduction method. AgCOFs are characterized by TEM, SEM, FTIR and XRD. At the same time, the catalytic ability of AgCOFs for trisodium citrate-AgNO3 nanosilver reaction is studied. The results show that AgCOFs can catalyze the reaction of trisodium citrate-AgNO3 to generate silver nanoparticles (AgNPs). The solution color of the system gradually changes from colorless to yellow, and the absorbance value increases. Based on the catalytic reaction of AgCOFs and the regulation effect of nucleic acid aptamer reaction on AgCOFs, a new "on-off-on" colorimetric analysis platform is constructed and applied to the detection of trace Pb2+ in water samples. This analytical platform is simple, sensitive and selective. Finally, the catalytic mechanism of the system is discussed to verify the feasibility of constructing a colorimetric analysis platform.

Pleural thickening induced by Glaesserella parasuis infection was linked to increased collagen and elastin.

Glaesserella parasuis is well-known for causing Glässer's disease, which costs the worldwide swine industry millions of dollars each year. It has been reported the symptom of pleural thickening during Glässer's disease but this symptom has received little attention. And there is no research on the elements which promote pleural thickening. In this study, pleural thickening was discovered to be associated with increased collagen fibers and elastic fibers. Furthermore, collagen-I and elastin were found to be up-regulated and concentrated in the pleura at the mRNA and protein levels following infection. To summarize, our findings add to the theoretical understanding of Glässer's disease and provide strong support for further research into the pathogenic mechanism of Glaesserella parasuis and the program's target treatment.

A comprehensive comparative study on LSD1 in different cancers and tumor specific LSD1 inhibitors.

LSD1 was significantly over-expressed in several cancer types, and its aberrant overexpression was revealed to play a crucial role in the initiation and progression of cancer. Several LSD1 inhibitors that were discovered and developed so far were found to be effective in attenuating tumor growth in both in vivo and in vitro studies. However, the major challenge associated with the development of cancer therapies is personalized treatment. Therefore, it is essential to look in detail at how LSD1 plays its part in carcinogenesis and whether there are any different expression levels of LSD1 in different tumors. Here in this review, fresh insight into a list of function correlated LSD1 binding proteins are provided, and we tried to figure out the role of LSD1 in different cancer types, including hematological malignancies and solid tumors. A critical description of mutation preference for LSD1 in different tumors was also discussed. Recent research findings clearly showed that the abrogation of LSD1 demethylase activity via LSD1 inhibitors markedly reduced the growth of cancer cells. But there are still many ambiguities regarding the role of LSD1 in different cancers. Therefore, targeting LSD1 for treating different cancers is still reductionist, and many challenges need to be met to improve the therapeutic outcomes of LSD1 inhibitors.

Clinical Manifestations of Supra-Large Range Nonperfusion Area in Diabetic Retinopathy.

Objective: We describe the clinical manifestations of supra-large range nonperfusion area (SLRNPA) in diabetic retinopathy (DR). Methods: This was a retrospective case-control study. A total of 260 eyes of 236 patients with DR who underwent pars plana vitrectomy in the Department of Ophthalmology of Qingdao Municipal Hospital from February 2016 to June 2019 were enrolled. Fundus fluorescein angiography was performed after surgery to determine whether SLRNPA or non-SLRNPA in DR was present. All demographic and clinical data were carefully collected. Results: Forty-one eyes of 22 patients were diagnosed with SLRNPA in DR (15.77% of all eyes). Compared to non-SLRNPA, SLRNPA patients were more likely to be male and younger with earlier DR onset, a smoking history, other comorbidities, and a higher HbA1c level. SLRNPA in DR eyes exhibited more neovascular glaucoma (NVG) and diabetic keratopathy (DK) than did other eyes. Such eyes were more likely to require anti-VEGF therapy before surgery or a silicone oil or a gas tamponade during surgery and to suffer from persistent corneal epithelial erosion and NVG recurrence after surgery. Conclusions: SLRNPA in DR is a severe status of DR. Treatment for DR patients with SLRNPA is difficult, and the prognosis is poor, so clinicians must thus pay more attention to SLRNPA in DR.

Intraocular myofibroblastoma tumour of the ciliary body: a case report and literature review.

BACKGROUND: Inflammatory Myofibroblastoma Tumors (IMTs) are extremely tumour rare in the intraocular. CASE PRESENTATION: A ciliary body tumor was found under slit lamp biomicroscopy in a 55-year-old male first diagnosed with cataract. Then this patient underwent trans-sclera resection via partial lamellar sclerouvectomy and par plans vitrectomy to remove the mass. Hematoxylin and eosin (HE) staining and immunohistochemistry findings showed that the characteristics of the tumor were consistent with IMT. CONCLUSIONS: We reported a rare case of intraocular IMT, which is confirmed by H&E staining, and IHC positive staining for Vimentin, Desmin and ALK, while negative staining for SMA, S-100, ki-67, CK, CD68, and calponin.

In situ Dispersed Nano-Au on Zr-Suboxides as Active Cathode for Direct CO2 Electroreduction in Solid Oxide Electrolysis Cells.

CO2 electrochemical reduction in solid oxide electrolysis cells is an effective way to combine CO2 conversion and renewable electricity storage. A Au layer is often used as a current collector, whereas Au nanoparticles are rarely used as a cathode because it is difficult to keep nanosized Au at high temperatures. Here we dispersed a Au layer into Au nanoparticles (down to 2 nm) at 800 °C by applying high voltages. A 75-fold decrease in the polarization resistance was observed, accompanied by a 38-fold improvement in the cell current density. Combining electronic microscopy, in situ near-ambient pressure X-ray photoelectron spectroscopy, and theoretical calculations, we found that the interface between the Au layer and the electrolyte (yttria-stabilized zirconia (YSZ)) was reconstructed into nano-Au/Zr-suboxide interfaces, which are active sites that show a much lower reaction activation energy than that of the Au/YSZ interface. The formation of Zr-suboxides promotes Au dispersion and Au nanoparticle stabilization due to the strong interaction between Au and Zr-suboxides.

Death by histone deacetylase inhibitor quisinostat in tongue squamous cell carcinoma via apoptosis, pyroptosis, and ferroptosis.

Tongue cancer is one of the most common oral malignancies. Quisinostat is a histone deacetylase inhibitor with antitumor activity. The aim of this study was to evaluate the effects of quisinostat on the viability of tongue squamous cell carcinoma (TSCC) cells (CAL-27, TCA-8113) in vitro and in vivo. Cell viability, cell morphological observation, scratch wound-healing assay, transwell migration assay, transmission electron microscope, flow cytometry and cellular reactive oxygen species were assessed in vitro. The results showed that quisinostat can significantly inhibit the viability, growth and migration of TSCC cells. And quisinostat could significantly induce TSCC cells apoptosis, pyroptosis, and ferroptosis. Quisinostat significantly inhibited tumor tissue growth in animal experiments. Up-regulation of the expression of Bax, cleaved-caspase3, caspase-1, p53, phospho-p53 and down-regulated of the expression of caspase-3, Bcl-2, GPX4 in cell lines and tumor tissues of nude mice were observed by Western blotting analysis. Up-regulation of the expression of caspase-1, Bax, cleaved-caspase3, p53 and down-regulated of the expression of ki67, caspase-3, Bcl-2, GPX4 in tumor tissues of nude mice were observed by immunohistochemistry. TUNEL analysis showed that quisinostat could increase the apoptosis rate in the tumor tissues of nude mice. Up-regulation of the expression of p53 and down-regulated expression of GPX4 in cell lines were observed by immunofluorescent staining, and the expression locations of p53 and GPX4 proteins in TSCC cells were observed. Based on these findings, quisinostat may be a potential drug for the treatment of tongue squamous cell carcinoma.

Identification of a linear epitope within domain I of Duck Tembusu virus envelope protein using a novel neutralizing monoclonal antibody.

Duck Tembusu virus (DTMUV) is a newly emerging pathogenic flavivirus that caused severe egg drop syndrome in laying ducks in China since 2010, leading to massive economic losses to the duck industry. Although the DTMUV E protein is considered to be critical in inducing the protective immune response, the functional epitopes within this protein remain largely unknown. In the present study, we isolated a DTMUV neutralizing monoclonal antibody (mAb) 3B8 from DTMUV E-immunized mice. Epitope mapping showed that mAb 3B8 recognized a novel linear epitope FSCLGMQNR located on the extreme N-terminal of the domain I (EDI) of E protein. Sequence alignment and Western blot analyses showed that the epitope is greatly conserved with high DTMUV-specificity. Moreover, upon cloning the heavy and light chain variable region sequences of mAb 3B8, we prepared the single-chain variable antibody fragment (scFv) 3B8 by connecting the two chains via a flexible peptide linker. The recombinant scFv 3B8 exhibited antiviral activity against DTMUV infection in vitro and in vivo. Our results provide valuable implications for the development of DTMUV vaccines and therapeutics.

P38 mitogen-activated protein kinase promotes Wnt/ß-catenin signaling by impeding Dickkofp-1 expression during Haemophilus parasuis infection.

Haemophilus parasuis induces severe acute systemic infection in pigs, characterized by fibrinous polyserositis, polyarthritis and meningitis. Our previous study demonstrated that H. parasuis induced the activation of p38 mitogen-activated protein kinase (MAPK) pathway, increasing the expression of proinflammatory genes and mediating H. parasuis-induced inflammation. Moreover, Wnt/ß-catenin signaling activation induced by H. parasuis disrupts the adherens junction between epithelial cells and initiates the epithelial-mesenchymal transition (EMT). In the present study, p38 MAPK was found to be involved in the accumulation of nuclear location of ß-catenin during H. parasuis infection in PK-15 and NPTr cells, via modulating the expression of dickkofp-1 (DKK-1), a negative regulator of Wnt/ß-catenin signaling. We generated DKK-1 knockout cell lines by CRISPR/Cas9-mediated genome editing in PK-15 and NPTr cells, and found that knockout of DKK-1 led to the dysfunction of p38 MAPK in regulating Wnt/ß-catenin signaling activity in H. parasuis-infected cells. Furthermore, p38 MAPK activity was independent of the activation of Wnt/ß-catenin signaling during H. parasuis infection. This is the first study to explore the crosstalk between p38 MAPK and Wnt/ß-catenin signaling during H. parasuis infection. It provides a more comprehensive view of intracellular signaling pathways during pathogenic bacteria-induced acute inflammation.

Construction of 1D/2D α-Fe2O3/SnO2 Hybrid Nanoarrays for Sub-ppm Acetone Detection.

Exhaled acetone is one of the representative biomarkers for the noninvasive diagnosis of type-1 diabetes. In this work, we have applied a facile two-step chemical bath deposition method for acetone sensors based on α-Fe2O3/SnO2 hybrid nanoarrays (HNAs), where one-dimensional (1D) FeOOH nanorods are in situ grown on the prefabricated 2D SnO2 nanosheets for on-chip construction of 1D/2D HNAs. After annealing in air, ultrafine α-Fe2O3 nanorods are homogenously distributed on the surface of SnO2 nanosheet arrays (NSAs). Gas sensing results show that the α-Fe2O3/SnO2 HNAs exhibit a greatly enhanced response to acetone (3.25 at 0.4 ppm) at a sub-ppm level compared with those based on pure SnO2 NSAs (1.16 at 0.4 ppm) and pure α-Fe2O3 nanorods (1.03 at 0.4 ppm), at an operating temperature of 340°C. The enhanced acetone sensing performance may be attributed to the formation of α-Fe2O3-SnO2 n-n heterostructure with 1D/2D hybrid architectures. Moreover, the α-Fe2O3/SnO2 HNAs also possess good reproducibility and selectivity toward acetone vapor, suggesting its potential application in breath acetone analysis.

COX-2 mediated crosstalk between Wnt/ß-catenin and the NF-κB signaling pathway during inflammatory responses induced by Haemophilus parasuis in PK-15 and NPTr cells.

Haemophilus parasuis infection causes typical acute systemic inflammation in pigs, is characterized by fibrinous polyserositis inflammation, and results in great economic losses to the swine industry worldwide. However, the molecular details of how the host modulates the acute inflammatory response induced by H. parasuis are largely unknown. In previous studies, we found that H. parasuis high-virulence strain SH0165 infection induced the activation of both Wnt/ß-catenin and NF-κB signaling in PK-15 and NPTr cells. In this study, we found that the activation of NF-κB, a central hub in inflammatory signaling, was impeded by the Wnt/ß-catenin pathway during H. parasuis infection. In contrast, blocking NF-κB activity had no effect on the Wnt/ß-catenin pathway during H. parasuis infection. Furthermore, we found that the inhibitory effect of ß-catenin on NF-κB activity was mediated by its target gene, pig cyclooxygenase-2 (COX-2). Therefore, we demonstrated that H. parasuis infection activates the canonical Wnt/ß-catenin signaling pathway, which leads to decreased NF-κB activity, reducing the acute inflammatory response in pigs. Additionally, the data provide a possible perspective for understanding the anti-inflammatory role of Wnt/ß-catenin in pigs during bacterial infection.