CDK5-mediated rearrangement of vimentin during Duck Tembusu virus infection inhibits viral replication.

Duck Tembusu virus (DTMUV) is a newly emerging pathogen that causes massive economic losses to the poultry industry in China and neighbouring countries. Vimentin, an intermediate filament protein, has been demonstrated to be involved in viral replication during infection. However, the specific role of vimentin in DTMUV replication has not been determined. In this study, we found that overexpression of vimentin in BHK-21 cells can inhibit DTMUV replication. Moreover, DTMUV replication was enhanced after vimentin expression was reduced in BHK-21 cells via small interfering RNA (siRNA). Further research indicated that DTMUV infection had no effect on the transcription or expression of vimentin. However, we found that DTMUV infection induced vimentin rearrangement, and the rearrangement of vimentin was subsequently confirmed to negatively modulate viral replication through the use of a vimentin network disrupting agent. Vimentin rearrangement is closely associated with its phosphorylation. Our experiments revealed that the phosphorylation of vimentin at Ser56 was promoted in the early stage of DTMUV infection. In addition, by inhibiting the phosphorylation of vimentin at Ser56 with a CDK5 inhibitor, vimentin rearrangement was suppressed, and DTMUV replication was significantly enhanced. These results indicated that DTMUV infection induced vimentin phosphorylation and rearrangement through CDK5, resulting in the inhibition of DTMUV replication. In summary, our study reveals a role for vimentin as a negative factor in the process of DTMUV replication, which helps to elucidate the function of cellular proteins in regulating DTMUV replication.

Efficacy and safety analysis of TACE + PEI + lenvatinib compared with TACE + lenvatinib for the treatment of hepatocellular carcinoma with PVTT: a retrospective study.

Objective: The aim of this study was to investigate the efficacy and safety of transcatheter arterial chemoembolization (TACE) combined with percutaneous ethanol injection (PEI) and lenvatinib in HCC patients with PVTT (Vp2-3), thus providing a safe and effective treatment strategy for advanced HCC patients. Materials and methods: Clinical data of 227 patients with unresectable HCC and PVTT treated at the Union Hospital from January 2018 to December 2021 were retrospectively analyzed. The patients were divided into two groups according to their treatment methods: TACE+PEI+lenvatinib group (N=103) and TACE+lenvatinib group (N=124). Results: The proportion of patients with disappearance, shrinkage, or no change of PVTT after treatment was significantly higher in the TACE+PEI+lenvatinib group compared to the TACE+lenvatinib group, with statistical significance (P<0.001). The TACE+PEI+lenvatinib group had higher objective response rate (ORR) (50.5% vs. 25.8%, P<0.001) and disease control rate (DCR) (87.4% vs. 74.2%, P=0.013) than the TACE+lenvatinib group. The median progression-free survival (mPFS) of the TACE+PEI+lenvatinib group was longer than that of the TACE+lenvatinib group (8.1 months vs. 6.5 months, P<0.001). Consistently, the median overall survival (mOS) of the TACE+PEI+lenvatinib group was longer than that of the TACE+lenvatinib group (17.1 months vs. 13.9 months, P<0.001). Conclusion: Among HCC patients with PVTT (Vp2-3), TACE+PEI+lenvatinib is more effective comparing to TACE+lenvatinib in prolonging PFS and OS. The control of PVTT in the TACE+PEI+lenvatinib group was significantly more satisfactory than that in the TACE+lenvatinib group. TACE+PEI+lenvatinib is a safe and effective treatment strategy for HCC patients with PVTT (Vp2-3).

Magnetic-free polarization rotation in an atomic vapor cell.

Magnetic-free nonreciprocal optical devices have attracted great attention in recent years. Here, we investigated the magnetic-free polarization rotation of light in an atom vapor cell. Two mechanisms of magnetic-free nonreciprocity have been realized in ensembles of hot atoms, including electromagnetically induced transparency and optically-induced magnetization. For a linearly polarized input probe light, a rotation angle up to 86.4° has been realized with external control and pump laser powers of 10 mW and is mainly attributed to the optically-induced magnetization effect. Our demonstration offers a new approach to realize nonreciprocal devices, which can be applied to solid-state atom ensembles and may be useful in photonic integrated circuits.

Risk assessment of pneumothorax in colorectal lung metastases treated by percutaneous thermal ablation: a multicenter retrospective cohort study.

PURPOSE: To evaluate the risk of pneumothorax in the percutaneous image-guided thermal ablation (IGTA) treatment of colorectal lung metastases (CRLM). METHODS: Data regarding patients with CRLM treated with IGTA from five medical institutions in China from 2016 to 2023 were reviewed retrospectively. Pneumothorax and non-pneumothorax were compared using the Student's t -test, χ 2 test and Fisher's exact test. Univariate logistic regression analysis was conducted to identify potential risk factors, followed by multivariate logistic regression analysis to evaluate the predictors of pneumothorax. Interactions between variables were examined and used for model construction. Receiver operating characteristic curves and nomograms were generated to assess the performance of the model. RESULTS: A total of 254 patients with 376 CRLM underwent 299 ablation sessions. The incidence of pneumothorax was 45.5%. The adjusted multivariate logistic regression model, incorporating interaction terms, revealed that tumour number [odds ratio (OR)=8.34 (95% CI: 1.37-50.64)], puncture depth [OR=0.53 (95% CI: 0.31-0.91)], pre-procedure radiotherapy [OR=3.66 (95% CI: 1.17-11.40)], peribronchial tumour [OR=2.32 (95% CI: 1.04-5.15)], and emphysema [OR=56.83 (95% CI: 8.42-383.57)] were significant predictive factors of pneumothorax (all P <0.05). The generated nomogram model demonstrated a significant prediction performance, with an area under the receiver operating characteristic curve of 0.800 (95% CI: 0.751-0.850). CONCLUSIONS: Pre-procedure radiotherapy, tumour number, peribronchial tumour, and emphysema were identified as risk factors for pneumothorax in the treatment of CRLM using percutaneous IGTA. Puncture depth was found to be a protective factor against pneumothorax.

Porcine circovirus type 2 and Glaesserella parasuis serotype 4 co-infection activates Snail1 to disrupt the intercellular junctions and facilitate bacteria translocation across the tracheal epithelium.

Clinically, Porcine circovirus type 2 (PCV2) often causes disease through coinfection with other bacterial pathogens, including Glaesserella parasuis (G. parasuis), which causes high morbidity and mortality. However, the mechanism of PCV2 and G. parasuis serotype 4 (GPS4) co-infection is still not fully understood. In this study, swine tracheal epithelial cells (STEC) were used as a barrier model, and our results showed that PCV2 infection increased the adhesion of GPS4 to STEC, while decreasing the levels of ZO-1, Occludin and increasing tracheal epithelial permeability, and ultimately facilitated GPS4 translocation. Snail1 is a transcriptional repressor, and has been known to induce epithelial-to-mesenchymal transition (EMT) during development or in cancer metastasis. Importantly, we found that Snail1, as a transcriptional repressor, was crucial in destroying the tracheal epithelial barrier induced by PCV2, GPS4, PCV2 and GPS4 coinfection. For the first time, we found that PCV2, GPS4, PCV2 and GPS4 coinfection cross-activates TGF-ß and p38/MAPK signaling pathways to upregulate the expression of Snail1, down-regulate the levels of ZO-1 and Occludin, and thus disrupt the integrity of tracheal epithelial barrier then promoting GPS4 translocation. Finally, PCV2 and GPS4 co-infection also can activate TGF-ß and p38/MAPK signaling pathways in vivo and upregulate Snail1, ultimately down-regulating the expression of ZO-1 and Occludin. Our study elucidates how PCV2 infection promotes GPS4 to breach the tracheal epithelial barrier and aggravate clinical manifestations.

Polycomb repressor complex: Its function in human cancer and therapeutic target strategy.

The Polycomb Repressor Complex (PRC) plays a pivotal role in gene regulation during development and disease, with dysregulation contributing significantly to various human cancers. The intricate interplay between PRC and cellular signaling pathways sheds light on cancer complexity. PRC presents promising therapeutic opportunities, with inhibitors undergoing rigorous evaluation in preclinical and clinical studies. In this review, we emphasize the critical role of PRC complex in gene regulation, particularly PcG proteins mediated chromatin compaction through phase separation. We also highlight the pathological implications of PRC complex dysregulation in various tumors, elucidating underlying mechanisms driving cancer progression. The burgeoning field of therapeutic strategies targeting PRC complexes, notably EZH2 inhibitors, has advanced significantly. However, we explore the need for combination therapies to enhance PRC targeted treatments efficacy, providing a glimpse into the future of cancer therapeutics.

First platelet transfusion refractoriness in a patient with acute myelocytic leukemia: A case report.

BACKGROUND: Platelet transfusion is of great significance in the treatment of thrombocytopenia caused by myelosuppression during intensive chemotherapy in patients with acute leukemia. In recent years, with platelet transfusion increasing, ineffective platelet transfusion has become increasingly prominent. Generally speaking, platelet antibodies can be produced after repeated transfusion, thus rendering subsequent platelet transfusion ineffective. We report a case of first platelet transfusion refractoriness (PTR) in a patient with acute myelocytic leukemia (AML). Due to the rarity of such cases in clinical practice, there have been no relevant case reports so far. CASE SUMMARY: A 51-year-old female patient attended the hospital due to throat pain and abnormal blood cells for 4 d. Her diagnosis was acute myelocytic leukemia [M2 type Fms related receptor tyrosine kinase 3, Isocitrate Dehydrogenase 1, Nucleophosmin 1, Neuroblastoma RAS viral oncogene homolog (+) high-risk group]. She was treated with "IA" (IDA 10 mg day 1-3 and Ara-C 0.2 g day 1-5) chemotherapy. When her condition improved, the patient was discharged from the hospital, instructed to take medicine as prescribed by the doctor after discharge, and returned to the hospital for further chemotherapy on time. CONCLUSION: We report a rare case of first platelet transfusion failure in a patient with AML during induction chemotherapy, which may be related to the production of platelet antibodies induced by antibiotics and excessive tumor load. This also suggests that we should consider the influence of antibiotics when the rare situation of first platelet transfusion failure occurs in patients with AML. When platelet antibodies are produced, immunoglobulins can be used to block antibodies, thereby reducing platelet destruction. For patients with PTR, both immune and non-immune factors need to be considered and combined in clinical practice along with individualized treatment to effectively solve the problem.

GPR35 acts a dual role and therapeutic target in inflammation.

GPR35 is a G protein-coupled receptor with notable involvement in modulating inflammatory responses. Although the precise role of GPR35 in inflammation is not yet fully understood, studies have suggested that it may have both pro- and anti-inflammatory effects depending on the specific cellular environment. Some studies have shown that GPR35 activation can stimulate the production of pro-inflammatory cytokines and facilitate the movement of immune cells towards inflammatory tissues or infected areas. Conversely, other investigations have suggested that GPR35 may possess anti-inflammatory properties in the gastrointestinal tract, liver and certain other tissues by curbing the generation of inflammatory mediators and endorsing the differentiation of regulatory T cells. The intricate role of GPR35 in inflammation underscores the requirement for more in-depth research to thoroughly comprehend its functional mechanisms and its potential significance as a therapeutic target for inflammatory diseases. The purpose of this review is to concurrently investigate the pro-inflammatory and anti-inflammatory roles of GPR35, thus illuminating both facets of this complex issue.

The dual M protein systems have diverse biological characteristics, but both contribute to M18-type Group A Streptococcus pathogenicity.

M protein is a key surface virulence factor in Group A Streptococcus (GAS), Group C Streptococcus (GCS), and other streptococcal species. GAS encodes M protein using the emm gene, while GCS employs the szm (or sem) gene. In M18-type GAS, dual M protein systems exist, comprising both GAS and GCS M proteins (encoded separately by emm18 and spa18). The spa18 gene in M18-type GAS shares a conserved region highly similar to GCS's szm gene. Our study reveals that spa18 exhibits higher transcription levels than emm18 in M18-type GAS strains. The dual M protein systems defective mutant (Δemm18Δspa18) displays a smooth surface, whereas wild-type and single M protein gene mutants remain rough. M18 and SPA18 proteins possess distinct characteristics, showing varied binding properties and cytotoxicity effects on macrophages (THP-1) and keratinocytes (HaCaT). Both emm18 and spa18 genes contribute to the skin pathogenicity of M18-type GAS. Transcriptome analysis suggests the potential involvement of the mga gene in spa18 transcription regulation, while SpyM18_2047 appears to be specific to spa18 regulation. In summary, this research offers a crucial understanding of the biological characteristics of dual M protein systems in M18-type GAS, highlighting their contributions to virulence and transcriptional regulation.

Membrane vesicle delivery of a streptococcal M protein disrupts the blood-brain barrier by inducing autophagic endothelial cell death.

M family proteins are critical virulence determinants of Streptococci. Streptococcus equi subsp. zooepidemicus (SEZ) are Group C streptococci that cause meningitis in animals and humans. SzM, the M protein of SEZ, has been linked to SEZ brain invasion. Here, we demonstrate that SzM is important in SEZ disruption of the blood-brain barrier (BBB). SEZ release SzM-bound membrane vesicles (MVs), and endocytosis of these vesicles by human brain endothelial microvascular cells (hBMECs) results in SzM-dependent cytotoxicity. Furthermore, administration of SzM-bound MVs disrupted the murine BBB. A CRISPR screen revealed that SzM cytotoxicity in hBMECs depends on PTEN-related activation of autophagic cell death. Pharmacologic inhibition of PTEN activity prevented SEZ disruption of the murine BBB and delayed mortality. Our data show that MV delivery of SzM to host cells plays a key role in SEZ pathogenicity and suggests that MV delivery of streptococcal M family proteins is likely a common streptococcal virulence mechanism.

Obstruction of the biliary tract as a rare presentation of acute myeloid leukemia: A case report.

To investigate the clinical characteristics of acute myeloid leukemia (AML) with biliary obstruction as the first manifestation and explore the treatment options. A retrospective analysis was performed on a case of AML with biliary obstruction as the first manifestation admitted to the First Affiliated Hospital of Jishou University (Jishou, China). The relevant laboratory examination, imaging, pathological results and treatment strategies were analyzed. The patient was a 44-year-old male with an initial manifestation of biliary obstruction. Combined with the results of laboratory tests and bone marrow aspiration, the patient was diagnosed with AML and was treated with an IA regimen (idarubicin 8 mg d1-3, cytarabine 0.2 d1-5). After 2 courses of treatment, complete response was achieved, the liver function returned to normal and the biliary obstruction disappeared. The initial symptoms of AML are varied, and always combine with multi-system organ damage. Early diagnosis and active treatment of primary diseases are the keys to improving the prognosis of these patients.

CsbD, a Novel Group B Streptococcal Stress Response Factor That Contributes to Bacterial Resistance against Environmental Bile Salts.

Group B Streptococcus (GBS) can cause many serious infections and result in severe symptoms depending on the infected organs. To survive and initiate infection from the gastrointestinal tract, GBS must resist physiochemical factors, such as bile salts, a potent antibacterial compound in the intestine. We found that GBS isolated from diverse sources all possess the capability to defend bile salts and permit survival. By constructing the GBS A909 transposon mutant library (A909Tn), we identified several candidate genes that might participate in the bile salt resistance of GBS. The rodA and csbD genes were validated as relevant to bile salt resistance. The rodA gene was anticipated to be related to peptidoglycan synthesis and influence the bile salt resistance of GBS by cell wall construction. Notably, we found that the csbD gene worked as a bile salt resistance response factor and influenced several ABC transporter genes, specifically at the later growth period of GBS under bile salt stress. We further detected the marked intracellular bile salt accumulation in ΔcsbD by hydrophilic interaction chromatography-liquid chromatography/mass spectrometry (HILIC-LC/MS). Collectively, we showed a novel GBS stress response factor, csbD, contributes to bacterial survival in bile salts by sensing bile salt stress and subsequently induces transcription of transporter genes to excrete bile salts. IMPORTANCE GBS, a conditional pathogenetic colonizer of the human intestinal flora, can cause severe infectious diseases in immunocompromised patients. Therefore, it is critical to understand the factors that contribute to the resistance to bile salts, which are abundant in the intestine but harmful to bacteria. We identified rodA and csbD genes involved in bile salt resistance using a transposon insertion site sequencing (TIS-seq) based screen. The rodA gene products might be involved in peptidoglycan synthesis as important contributors to stress resistance including bile salts. However, the csbD gene conferred bile salt resistance by promoting transporter genes transcription at the later growth period of GBS in response to bile salts. These findings developed a better understanding of the stress response factor csbD on the bile salt resistance of GBS.

A link between STK signalling and capsular polysaccharide synthesis in Streptococcus suis.

Synthesis of capsular polysaccharide (CPS), an important virulence factor of pathogenic bacteria, is modulated by the CpsBCD phosphoregulatory system in Streptococcus. Serine/threonine kinases (STKs, e.g. Stk1) can also regulate CPS synthesis, but the underlying mechanisms are unclear. Here, we identify a protein (CcpS) that is phosphorylated by Stk1 and modulates the activity of phosphatase CpsB in Streptococcus suis, thus linking Stk1 to CPS synthesis. The crystal structure of CcpS shows an intrinsically disordered region at its N-terminus, including two threonine residues that are phosphorylated by Stk1. The activity of phosphatase CpsB is inhibited when bound to non-phosphorylated CcpS. Thus, CcpS modulates the activity of phosphatase CpsB thereby altering CpsD phosphorylation, which in turn modulates the expression of the Wzx-Wzy pathway and thus CPS production.

Development and Characterization of Fluorescent Probes for the G Protein-Coupled Receptor 35.

The orphan G protein-coupled receptor 35 (GPR35) is a potential target for the treatment of pain, inflammation, and metabolic diseases. Although many GPR35 agonists have been discovered, research on functional GPR35 ligands, such as fluorescent probes, is still limited. Herein, we developed a series of GPR35 fluorescent probes by conjugating a BODIPY fluorophore to DQDA, a known GPR35 agonist. All probes exhibited excellent GPR35 agonistic activity and desired spectroscopic properties, as determined by the DMR assay, bioluminescence resonance energy transfer (BRET)-based saturation, and kinetic binding experiments. Notably, compound 15 showed the highest binding potency and the weakest nonspecific BRET binding signal (K d = 3.9 nM). A BRET-based competition binding assay with 15 was also established and used to determine the binding constants and kinetics of unlabeled GPR35 ligands.

Antibody-dependent enhancement of porcine reproductive and respiratory syndrome virus infection downregulates the levels of interferon-gamma/lambdas in porcine alveolar macrophages in vitro.

Fc gamma receptor-mediated antibody-dependent enhancement (ADE) can promote virus invasion of target cells, sometimes exacerbating the severity of the disease. ADE may be an enormous hurdle to developing efficacious vaccines for certain human and animal viruses. ADE of porcine reproductive and respiratory syndrome virus (PRRSV) infection has been demonstrated in vivo and in vitro. However, the effect of PRRSV-ADE infection on the natural antiviral immunity of the host cells is yet to be well investigated. Specifically, whether the ADE of PRRSV infection affects the levels of type II (interferon-gamma, IFN-γ) and III (interferon-lambdas, IFN-λs) interferons (IFNs) remains unclear. In this study, our results showed that PRRSV significantly induced the secretion of IFN-γ, IFN-λ1, IFN-λ3, and IFN-λ4 in porcine alveolar macrophages (PAMs) in early infection, and weakly inhibited the production of IFN-γ, IFN-λ1, IFN-λ3, and IFN-λ4 in PAMs in late infection. Simultaneously, PRRSV infection significantly increased the transcription of interferon-stimulated gene 15 (ISG15), ISG56, and 2', 5'-oligoadenylate synthetase 2 (OAS2) in PAMs. In addition, our results showed that PRRSV infection in PAMs via the ADE pathway not only significantly decreased the synthesis of IFN-γ, IFN-λ1, IFN-λ3, and IFN-λ4 but also significantly enhanced the generation of transforming growth factor-beta1 (TGF-ß1). Our results also showed that the ADE of PRRSV infection significantly reduced the mRNAs of ISG15, ISG56, and OAS2 in PAMs. In conclusion, our studies indicated that PRRSV-ADE infection suppressed innate antiviral response by downregulating the levels of type II and III IFNs, hence facilitating viral replication in PAMs in vitro. The ADE mechanism demonstrated in the present study furthered our understanding of persistent pathogenesis following PRRSV infection mediated by antibodies.

Asymmetric Cross Metasurfaces with Multiple Resonances Governed by Bound States in the Continuum.

The bound state in the continuum (BIC) has paved a new way to achieve excellent localization of the resonant mode coexisting with a continuous spectrum in the metasurface. Here, we propose an all-dielectric metasurface consisting of periodic pairs of asymmetric crosses that supports multiple Fano resonances. Due to the sufficient degrees of freedom in the unit cell, we displaced the vertical bars horizontally to introduce in-plane perturbation, doubling the unit cell structure. Dimerization directly resulted in the folding of the Brillouin zone in k space and transformed the BIC modes into quasi-BIC resonances. Then, simultaneous in-plane symmetry breaking was introduced in both the x and y directions to excite two more resonances. The physical mechanisms of these BIC modes were investigated by multipole decomposition of the scattering cross section and electromagnetic near-field analysis, confirming that they are governed by toroidal dipole (TD) modes and magnetic dipole (MD) modes. We also investigated the flexible tunability and evaluated the sensing performance of our proposed metasurface. Our work is promising for different applications requiring stable and tunable resonances, such as optical switching and biomolecule sensing.

Phosphorylation of GntR reduces Streptococcus suis oxidative stress resistance and virulence by inhibiting NADH oxidase transcription.

GntR transcription factor of Streptococcus suis serotype 2 (SS2) is a potential substrate protein of STK, but the regulation mechanisms of GntR phosphorylation are still unclear. This study confirmed that STK phosphorylated GntR in vivo, and in vitro phosphorylation experiments showed that STK phosphorylated GntR at Ser-41. The phosphomimetic strain (GntR-S41E) had significantly reduced lethality in mice and reduced bacterial load in the blood, lung, liver, spleen, and brain of infected mice compared to wild-type (WT) SS2. Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) experiments demonstrated that the promoter of nox was bound by GntR. The phosphomimetic protein GntR-S41E cannot bind to the promoter of nox, and the nox transcription levels were significantly reduced in the GntR-S41E mutant compared to WT SS2. The virulence in mice and the ability to resist oxidative stress of the GntR-S41E strain were restored by complementing transcript levels of nox. NOX is an NADH oxidase that catalyzes the oxidation of NADH to NAD+ with the reduction of oxygen to water. We found that NADH is likely accumulated under oxidative stress in the GntR-S41E strain, and higher NADH levels resulted in increased amplified ROS killing. In total, we report GntR phosphorylation could inhibit the transcription of nox, which impaired the ability of SS2 to resist oxidative stress and virulence.

Coinfection with porcine circovirus type 2 and Glaesserella parasuis serotype 4 enhances pathogenicity in piglets.

Coinfection of Porcine circovirus type 2 (PCV2) and Glaesserella parasuis type 4 (GPS4) is widespread clinically, resulting in high morbidity and mortality, however, interactions between the two pathogens during coinfection and the coinfection pathogenesis are poorly understood. In this study, a piglet model coinfected with PCV2 and GPS4 was established; coinfection of the piglets' group showed more obvious symptoms, such as high fever and emaciation, and more severe histological lesions appeared in various organs. Importantly, piglets in the coinfection group produced lower levels of PCV2 and GPS4 antibodies, and showed high levels of inflammatory cytokines, TLR2, and TLR4, while the levels of CD4, CD8, MHC II, costimulatory molecules, and IL-12p40 were decreased. In addition, a model of macrophage 3D4/21 cells coinfection with PCV2 and GPS4 was established, coinfected cells exhibited increased expression of the cytokines IL-6, IL-8, TNF-α, IL-1ß, and the receptors TLR2, TLR4, while decreased MHC II. We further demonstrate that cytokine production is associated with the activation of NF-κB and NLRP3 inflammasome signaling pathways, and TLR4 is also involved. Altogether, our findings suggest that coinfection with PCV2 and GPS4 exacerbates the inflammatory response, resulting in severe tissue damage, and probably impaired macrophage antigen presentation and T cell activation, resulting in immune dysregulation, aggravating host infection.

Vimentin affects inflammation and neutrophil recruitment in airway epithelium during Streptococcus suis serotype 2 infection.

Streptococcus suis serotype 2 (SS2) frequently colonizes the swine upper respiratory tract and can cause Streptococcal disease in swine with clinical manifestations of pneumonia, meningitis, and septicemia. Previously, we have shown that vimentin, a kind of intermediate filament protein, is involved in the penetration of SS2 through the tracheal epithelial barrier. The initiation of invasive disease is closely related to SS2-induced excessive local inflammation; however, the role of vimentin in airway epithelial inflammation remains unclear. Here, we show that vimentin deficient mice exhibit attenuated lung injury, diminished production of proinflammatory cytokines interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and the IL-8 homolog, keratinocyte-derived chemokine (KC), and substantially reduced neutrophils in the lungs following intranasal infection with SS2. We also found that swine tracheal epithelial cells (STEC) without vimentin show decreased transcription of IL-6, TNF-α, and IL-8. SS2 infection caused reassembly of vimentin in STEC, and pharmacological disruption of vimentin filaments prevented the transcription of those proinflammatory cytokines. Furthermore, deficiency of vimentin failed to increase the transcription of nucleotide oligomerization domain protein 2 (NOD2), which is known to interact with vimentin, and the phosphorylation of NF-κB protein p65. This study provides insights into how vimentin promotes excessive airway inflammation, thereby exacerbating airway injury and SS2-induced systemic infection.

Impacts of microplastic-petroleum pollution on nutrient uptake, growth, and antioxidative activity of Chlorella vulgaris.

As one of the emerging pollutants, microplastics (MPs; <5 mm) can interact with co-contaminants such as petroleum in marine aquatic systems, and their combined toxicity has not been fully investigated. Therefore, this study focused on pollutants such as micro-sized polyethylene (mPE) and petroleum, aiming to explore their single and combined toxicities to microalga Chlorella vulgaris in terms of the cell growth, antioxidative enzymes, and nutrients utilization. The results showed that the MPs alone (particle sizes (i.e., 13, 165, 550 µm), concentrations (i.e., 0.01, 0.1, and 1 g/L), and aging degrees (i.e., aged for 0 d and 90 d under UVA)), and petroleum alone (5% water accommodated fraction, WAF), and their combinations (i.e., 5% WAF + 165 µm-0.1 g/L-aged 0 d mPE, 5% WAF + 165 µm-0.1 g/L-aged 90 d mPE) all posed toxicities risk to C. vulgaris, following an increase in oxidative stress. The cellular utilization of elements such as Fe, Si, Ca, and Mg was inhibited, whereas the uptake of Mn, NO3--N, and PO43--P increased as compared to the control experiments. Furthermore, the relationship between nutrients and growth indicators was analyzed using a structural equation model. The results indicated that Fe and Mn directly affected the indirect NO3--N absorption by C. vulgaris, which indirectly affected the dry cell weight (DCW) of the microalgae. The path coefficient of Fe and Mn affecting nitrate was 0.399 and 0.388, respectively. The absorption of N was the key step for C. vulgaris resist stress. This study provides a novel analysis of the effects of MPs on the growth of microalgae from the perspective of nutrient elements, thereby providing a useful basis for further exploration of the associated mechanisms.