Antennal transcriptome analysis of Psyttalia incisi (silvestri) (Hymenoptera: Braconidae): identification and tissue expression profiling of candidate odorant-binding protein genes.

BACKGROUND: Olfaction plays an important role in host-seeking by parasitoids, as they can sense chemical signals using sensitive chemosensory systems. Psyttalia incisi (Silvestri) (Hymenoptera: Braconidae) is the dominant parasitoid of Bactrocera dorsalis (Hendel) in fruit-producing regions of southern China. The olfactory behavior of P. incisi has been extensively studied; however, the chemosensory mechanisms of this species are not fully understood. RESULTS: Bioinformatics analysis of 64,515 unigenes from the antennal transcriptome of both male and female adults P. incisi identified 87 candidate chemosensory genes. These included 13 odorant-binding proteins (OBPs), seven gustatory receptors (GRs), 55 odorant receptors (ORs), 10 ionotropic receptors (IRs), and two sensory neuron membrane proteins (SNMPs). Phylogenetic trees were constructed to predict evolutionary relationships between these chemosensory genes in hymenopterans. Moreover, the tissue expression profiles of 13 OBPs were analyzed by quantitative real-time PCR, revealing high expression of seven OBPs (1, 3, 6, 7, 8, 12, and 13) in the antennae. CONCLUSION: This study represents the first identification of chemosensory genes and the determination of their expression patterns in different tissues of P. incisi. These results contribute to a better understanding of the function of the chemosensory system of this parasitoid species.

Effects of low-concentration spinetoram wax-based bait stations on Bactrocera dorsalis (Diptera: Tephritidae).

Spinetoram wax-based bait station (SWBB) is a maintenance-free, long-lasting, and eco-friendly management measure for Bactrocera dorsalis. However, the impacts of low-concentration spinetoram on B. dorsalis have not yet been determined. Therefore, our study aimed to determine the impacts of low-concentration SWBBs on the biology, demographics, detoxifying enzymes, and gut microorganisms of B. dorsalis. Our results showed that low-concentration SWBBs posed dose-dependent effects on the lifespan and fecundity of B. dorsalis adults. Both the LC10 and LC30 treatments significantly reduced the fecundity, while only the latter led to significant deleterious effects on the longevity of adults. Transgenerational bioassays revealed that exposure to LC30 significantly affected the development period of larvae and pupae as well as the livability of pre-adult stage of the progeny. However, except for the ovipositional period, no significant effects on the biological traits of F1 adults were observed. In terms of the F1 demographic parameters, dose-dependent effects were observed. Moreover, both the LC10 and LC30 treatments significantly extended the mean generation time, while the latter remarkably decreased the finite and intrinsic rates. Additionally, the significant induction of CarE activity by the LC10 and LC30 treatment was maintained until 24 and 48 h respectively. The CYP450 O-deethylation activity in the LC30 treatment was significantly enhanced at 24 and 48 h intervals when compared to the control. Regarding the intestinal bacterial community, after B. dorsalis adults were exposed to low-concentration SWBBs, the relative abundances of Providencia and Vagococcus were significantly increased, whereas those of Lactococcus and Brachyspira experienced a significant decrease. The obtained results are expected to serve as a foundation for the application of spinetoram in "lure-and-kill" strategies against B. dorsalis.

Combining multi-isotope technology, hydrochemical information, and MixSIAR model to identify and quantify nitrate sources of groundwater and surface water in a multi-land use region.

Accurate identification of nitrate (NO3-) sources is the premise of non-point source pollution control in watersheds. The multiple isotope techniques (δ15N-NO3-, δ18O-NO3-, δ2H-H2O, δ18O-H2O), combined with hydrochemistry characteristics, land use information, and Bayesian stable isotope mixing model (MixSIAR), were used to identify the sources and contributions of NO3- in the agricultural watershed of the upper Zihe River, China. A total of 43 groundwater (GW) and 7 surface water (SFW) samples were collected. The results showed that NO3- concentrations of 30.23% GW samples exceeded the WHO maximum permissible limit level, whereas SFW samples did not exceed the standard. The NO3- content of GW varied significantly among different land uses. The averaged GW NO3- content in livestock farms (LF) was the highest, followed by vegetable plots (VP), kiwifruit orchards (KF), croplands (CL), and woodlands (WL). Nitrification was the main transformation process of nitrogen, while denitrification was not significant. Hydrochemical analysis results combined with NO isotopes biplot showed that manure and sewage (M&S), NH4+ fertilizers (NHF), and soil organic nitrogen (SON) were the mixed sources of NO3-. The MixSIAR model summarized that M&S was the main NO3- contributor for the entire watershed, SFW, and GW. For contribution rates of sources in GW of different land use patterns, the main contributor in KF was M&S (contributing 59.00% on average), while M&S (46.70%) and SON (33.50%) contributed significantly to NO3- in CL. Combined with the traceability results and the situation that land use patterns are changing from CL to KF in this area, improving fertilization patterns and increasing manure use efficiency are necessary to reduce NO3- input. These research results will serve as a theoretical foundation for controlling NO3- pollution in the watershed and adjusting agricultural planting structures.

Collateral sensitivity between tetracyclines and aminoglycosides constrains resistance evolution in carbapenem-resistant Klebsiella pneumoniae.

AIMS: The acquisition of resistance to one antibiotic may confer an increased sensitivity to another antibiotic in bacteria, which is an evolutionary trade-off between different resistance mechanisms, defined as collateral sensitivity (CS). Exploiting the role of CS in treatment design could be an effective method to suppress or even reverse resistance evolution. METHODS: Using experimental evolution, we systematically studied the CS between aminoglycosides and tetracyclines in carbapenem-resistant Klebsiella pneumoniae (CRKP) and explored the underlying mechanisms through genomic and transcriptome analyses. The application of CS-based therapies for resistance suppression, including combination therapy and alternating antibiotic therapy, was further evaluated in vitro and in vivo. RESULTS: Reciprocal CS existed between tetracyclines and aminoglycosides in CRKP. The increased sensitivity of aminoglycoside-resistant strains to tetracyclines was associated with the alteration of bacterial membrane potential, whereas the unbalanced oxidation-reduction process of tetracycline-resistant strains may lead to an increased bacterial sensitivity to aminoglycosides. CS-based combination therapy could efficiently constrain the evolution of CRKP resistance in vitro and in vivo. In addition, alternating antibiotic therapy can re-sensitize CRKP to previously resistant drugs, thereby maintaining the trade-off. CONCLUSIONS: These results provide new insights into constraining the evolution of CRKP resistance through CS-based therapies.

Construction of a redox-related gene signature for overall survival prediction and immune infiltration in non-small-cell lung cancer.

Background: An imbalance in the redox homeostasis has been reported in multiple cancers and is associated with a poor prognosis of disease. However, the prognostic value of redox-related genes in non-small-cell lung cancer (NSCLC) remains unclear. Methods: RNA sequencing data, DNA methylation data, mutation, and clinical data of NSCLC patients were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus databases. Redox-related differentially expressed genes (DEGs) were used to construct the prognostic signature using least absolute shrinkage and selection operator (LASSO) regression analysis. Kaplan-Meier survival curve and receiver operator characteristic (ROC) curve analyses were applied to validate the accuracy of the gene signature. Nomogram and calibration plots of the nomogram were constructed to predict prognosis. Pathway analysis was performed using gene set enrichment analysis. The correlations of risk score with tumor stage, immune infiltration, DNA methylation, tumor mutation burden (TMB), and chemotherapy sensitivity were evaluated. The prognostic signature was validated using GSE31210, GSE26939, and GSE68465 datasets. Real-time polymerase chain reaction (PCR) was used to validate dysregulated genes in NSCLC. Results: A prognostic signature was constructed using the LASSO regression analysis and was represented as a risk score. The high-risk group was significantly correlated with worse overall survival (OS) (p < 0.001). The area under the ROC curve (AUC) at the 5-year stage was 0.657. The risk score was precisely correlated with the tumor stage and was an independent prognostic factor for NSCLC. The constructed nomogram accurately predicted the OS of patients after 1-, 3-, and 5-year periods. DNA replication, cell cycle, and ECM receptor interaction were the main pathways enriched in the high-risk group. In addition, the high-risk score was correlated with higher TMB, lower methylation levels, increased infiltrating macrophages, activated memory CD4+ T cells, and a higher sensitivity to chemotherapy. The signature was validated in GSE31210, GSE26939, and GSE68465 datasets. Real-time PCR validated dysregulated mRNA expression levels in NSCLC. Conclusions: A prognostic redox-related gene signature was successfully established in NSCLC, with potential applications in the clinical setting.

A ferroptosis-related gene signature for overall survival prediction and immune infiltration in lung squamous cell carcinoma.

BACKGROUND: Ferroptosis is associated with cancer initiation and progression. However, the molecular mechanism and prognostic value of ferroptosis-related genes in lung squamous cell carcinoma (LUSC) are poorly understood. METHODS: The mRNA expression profiles, methylation data, and clinical information of patients with LUSC were downloaded from TCGA and GEO database. Ferroptosis-related differentially expressed genes (DEGs) were identified between cancerous and non-cancerous tissues, and their prognostic value was systemically investigated by bioinformatic analyses. RESULTS: A ferroptosis-related gene signature (ALOX5, TFRC, PHKG2, FADS2, NOX1) was constructed using multivariate Cox regression analysis and represented as a risk score. Overall survival (OS) probability was significantly lower in the high-risk group than in the low-risk group (P<0.001), and receiver operating characteristic curve showed a good predictive capacity (AUC = 0.739). The risk score was an independent prognostic factor for LUSC. A nomogram was constructed to predict the OS probabilities at 1, 3, and 5 years. High-risk score was associated with increased immune infiltration, lower methylation levels, higher immune checkpoint genes expression levels, and better chemotherapy response. Cell adhesion molecules, focal adhesion, and extracellular matrix receptor interaction were the main pathways in the high-risk group. The signature was validated using the TCGA test cohort, entire TCGA cohort, GSE30219, GSE157010, GSE73403, and GSE4573 datasets. The gene disorders in patients with LUSC were validated using real-time PCR and single-cell RNA sequencing analysis. CONCLUSIONS: A ferroptosis-related gene signature was constructed to predict OS probability in LUSC. This could facilitate novel therapeutic methods and guide individualized therapy.

The complete mitochondrial genome of Psyttalia incisi (Silvestri, 1916) (Hymenoptera: Braconidae).

Psyttalia incisi (Silvestri, 1916), an important solitary opiinae endoparasitoid, plays a crucial role in biological control programs against tephritid pests. In this study, the entire mitochondrial (mt) genome of P. incisi was sequenced and characterized. The whole mitogenome of P. incisi is 15,188 bp long with a G + C content of 14.80%, and encodes all 37 genes that are typically found in animal mt genomes, which contains 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs), and two ribosomal RNA genes (rRNAs). A maximum-likelihood (ML) tree demonstrates that P. incisi is closely related to Psyttalia lounsburyi, Psyttalia humilis, and Psyttalia concolor.

Cefiderocol for the Treatment of Multidrug-Resistant Gram-Negative Bacteria: A Systematic Review of Currently Available Evidence.

Cefiderocol is a novel synthetic siderophore-conjugated antibiotic that hijacks the bacterial iron transport systems facilitating drug entry into cells, achieving high periplasmic concentrations. This systematic review analyzed the currently available literature on cefiderocol. It summarized in vitro susceptibility data, in vivo antimicrobial activity, pharmacokinetics/pharmacodynamics (PK/PD), clinical efficacy, safety and resistance mechanisms of cefiderocol. Cefiderocol has potent in vitro and in vivo activity against multidrug-resistant (MDR) Gram-negative bacteria, including carbapenem-resistant isolates. But New Delhi Metallo-ß-lactamase (NDM)- positive isolates showed significantly higher MICs than other carbapenemase-producing Enterobacterales, with a susceptible rate of 83.4% for cefiderocol. Cefiderocol is well-tolerated, and the PK/PD target values can be achieved using a standard dose regimen or adjusted doses according to renal function. Clinical trials demonstrated that cefiderocol was non-inferiority to the comparator drugs in treating complicated urinary tract infection and nosocomial pneumonia. Case reports and series showed that cefiderocol was a promising therapeutic agent in carbapenem-resistant infections. However, resistant isolates and reduced susceptibility during treatment to cefiderocol have already been reported. In conclusion, cefiderocol is a promising powerful weapon for treating MDR recalcitrant infections.

Efficacy of wax-based bait stations for controlling Bactrocera dorsalis (Diptera: Tephritidae).

BACKGROUND: Bactrocera dorsalis is a notorious pest and spraying of insecticides has been the major approach to controlling its damage. However, insecticide abuse has led to negative impacts on public health and insecticide resistance; hence, sustainable strategies, such as bait stations, need to be developed and taken into account for B. dorsalis management. In this study, we integrated insecticide, sugar, olfactory and visual elements into a wax matrix to formulate a long-lasting bait station. We determined its efficacy against B. dorsalis under field conditions. RESULTS: The optimal bait station was a wax matrix incorporated with 1% spinetoram, 1% yellow pigment, and 3% ammonium acetate, and was spherical in shape with a 6 cm diameter. The longevity of this bait station was at least 10 weeks under field conditions. In a release and recapture experiment performed in Orchard 1, the bait stations were as effective as bait spray in controlling sterile fly populations, and more effective than the control. In a 2-year field trial conducted in Orchard 2, the number of female B. dorsalis and fruit infestation in the area where bait stations had been deployed was similar to the areas treated with cover spray. In Orchard 3, deployment of bait stations combined with chemical cover spray treatment decreased the population of female B. dorsalis and fruit damage more effectively than cover spray alone. CONCLUSIONS: Overall, wax-based bait stations can be regarded as a viable alternative to insecticides or a synergistic method for managing B. dorsalis. © 2022 Society of Chemical Industry.

Fudosteine attenuates acute lung injury in septic mice by inhibiting pyroptosis via the TXNIP/NLRP3/GSDMD pathway.

There is a dearth of effective pharmacotherapies for sepsis-induced acute lung injury/acute respiratory distress syndrome (ALI/ARDS) to which oxidative stress and excessive inflammation are major contributors. We hypothesized that fudosteine, a cysteine derivative, may protect against sepsis-induced ALI/ARDS given its anti-oxidant capacity. This study aimed to investigate the effects and mechanisms of fudosteine in a mouse model of sepsis-induced ALI. Sepsis was induced by cecal ligation and puncture (CLP). The intragastrical administration of fudosteine (25 mg/kg, 50 mg/kg, and 100 mg/kg) dose-dependently decreased proinflammatory cytokine levels in bronchoalveolar lavage fluid (BALF) and serum and reduced BALF/serum albumin and lung wet/dry weight ratios in septic mice. The lung injury score was significantly lowered by fudosteine [e.g., 0.18 ± 0.03 (100 mg/kg) vs. 0.42 ± 0.03 (CLP), P < 0.0001]. Fudosteine also reduced the biomarkers of lung epithelial injury in BALF and markedly improved oxidative stress indicators in lung tissues [e.g., malondialdehyde: 337.70 ± 23.78 (100 mg/kg) vs. 686.40 ± 28.36 (CLP) nmol/mg protein, P < 0.0001]. Lung tissue transcriptomics analyses revealed suppressed inflammatory responses and oxidative stress with fudosteine and the involvement of the inflammasome and pyroptosis pathways. Western blot analyses indicated that fudosteine inhibited the sepsis-induced activation of gasdermin D (GSDMD) and caspase-1 and the upregulation of thioredoxin-interacting protein (TXNIP), nucleotide-binding domain, leucine-rich repeat-containing receptor, pyrin domain-containing-3 (NLRP3), and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC). Fudosteine therefore protects against sepsis-induced ALI in mice, and the inhibition of pyroptosis via the TXNIP/NLRP3/GSDMD pathway may be an underlying mechanism.

The complete mitochondrial genome of Fopius arisanus (Sonan 1932) (Hymenoptera: Braconidae).

Fopius arisanus (Sonan, 1932), an important egg parasitoid of several notorious tephritid pests, plays a key role in biological control programs. In the present study, the whole mitochondrial genome of F. arisanus was sequenced and characterized. The mitogenome of F. arisanus is 16,425 bp in length with 14.94% GC content, and contains 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs), and two ribosomal RNA genes (rRNAs). The phylogenetic trees demonstrated that F. arisanus is sister group to Psyttalia concolor, P. humilis, P. lounsburyi and Diachasmimorpha longicaudata.

Mitochondrial-Targeting Antioxidant SS-31 Suppresses Airway Inflammation and Oxidative Stress Induced by Cigarette Smoke.

This study investigated whether the mitochondrial-targeted peptide SS-31 can protect against cigarette smoke- (CS-) induced airway inflammation and oxidative stress in vitro and in vivo. Mice were exposed to CS for 4 weeks to establish a CS-induced airway inflammation model, and those in the experimental group were pretreated with SS-31 1 h before CS exposure. Pathologic changes and oxidative stress in lung tissue, inflammatory cell counts, and proinflammatory cytokine levels in bronchoalveolar lavage fluid (BALF) were examined. The mechanistic basis for the effects of SS-31 on CS extract- (CSE-) induced airway inflammation and oxidative stress was investigated using BEAS-2B bronchial epithelial cells and by RNA sequencing and western blot analysis of lung tissues. SS-31 attenuated CS-induced inflammatory injury of the airway and reduced total cell, neutrophil, and macrophage counts and tumor necrosis factor- (TNF-) α, interleukin- (IL-) 6, and matrix metalloproteinase (MMP) 9 levels in BALF. SS-31 also attenuated CS-induced oxidative stress by decreasing malondialdehyde (MDA) and myeloperoxidase (MPO) activities and increasing that of superoxide dismutase (SOD). It also reversed CS-induced changes in the expression of mitochondrial fission protein (MFF) and optic atrophy (OPA) 1 and reduced the amount of cytochrome c released into the cytosol. Pretreatment with SS-31 normalized TNF-α, IL-6, and MMP9 expression, MDA and SOD activities, and ROS generation in CSE-treated BEAS-2B cells and reversed the changes in MFF and OPA1 expression. RNA sequencing and western blot analysis showed that SS-31 inhibited CS-induced activation of the mitogen-activated protein kinase (MAPK) signaling pathway in vitro and in vivo. Thus, SS-31 alleviates CS-induced airway inflammation and oxidative stress via modulation of mitochondrial function and regulation of MAPK signaling and thus has therapeutic potential for the treatment of airway disorders caused by smoking.

Effect of Cold Storage on the Quality of Psyttalia incisi (Hymenoptera: Braconidae), a Larval Parasitoid of Bactrocera dorsalis (Diptera: Tephritidae).

Psyttalia incisi (Silvestri) is the dominant parasitoid against Bactrocera dorsalis (Hendel) in fruit-producing regions of southern China. Prior to a large-scale release, it is important to generate a sufficient stockpile of P. incisi whilst considering how best to maintain their quality and performance; cold storage is an ideal method to achieve these aims. In this study, the impacts of temperature and storage duration on the developmental parameters of P. incisi pupae at different age intervals were assessed. Then, four of the cold storage protocols were chosen for further evaluating their impacts on the quality parameters of post-storage adults. Results showed that the emergence rate of P. incisi was significantly affected by storage temperature, storage duration, and pupal age interval and their interactions. However, when late-age P. incisi pupae developed at a temperature of 13 °C for 10 or 15 d, no undesirable impacts on dry weight, flight ability, longevity, reproduction parameters of post-storage adults, emergence rate, or the female proportion of progeny were recorded. Our findings demonstrate that cold storage has the potential for enhancing the flexibility and effectiveness of the large-scale production and application of P. incisi.

Knockout of Formyl Peptide Receptor-1 Attenuates Cigarette Smoke-Induced Airway Inflammation in Mice.

Objective: The formyl peptide receptor-1 (FPR-1) has been reported to be implicated in the regulation of inflammatory disorders, while its role in cigarette smoke (CS)-induced airway inflammation has not been fully explained. In this study, we investigated the role of FPR-1 in CS-induced airway inflammation and the possible mechanism through gene knockout (KO) technology and transcriptional study. Methods: FPR-1 KO or wild-type C57BL/6 mice were exposed to mainstream CS to establish an airway inflammation model. Cell counts and pro-inflammatory cytokines were measured in bronchoalveolar lavage fluid (BALF). Lung tissues were collected for histological examination, polymerase chain reaction, Western blot, transcriptomic gene study, and related bioinformatics analysis. Results: CS exposure induced significant histological inflammatory changes, increased neutrophils, and pro-inflammatory cytokines in the BALF of wild-type mice, which were all attenuated by KO of FPR-1. The transcriptomic gene study showed a total of 198 up-regulated genes and 282 down-regulated genes in mouse lungs. Bioinformatics analysis including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) suggested these differentiated expressed genes were significantly related to the immune, chemotaxis responses, and cross-talked with a complicated network of signaling pathways including NF-κB. Western blot validated that KO of FPR-1 inhibited CS-induced NF-κB activation. Conclusion: Knockout of FPR-1 significantly ameliorates CS-induced airway inflammation in mice, possibly via its related immune-chemotaxis responses and inhibition of NF-κB activation.

In vitro and in vivo synergistic effects of tigecycline combined with aminoglycosides on carbapenem-resistant Klebsiella pneumoniae.

OBJECTIVES: Carbapenem-resistant Klebsiella pneumoniae (CR-KP) infections represent severe threats to public health worldwide. The aim of this study was to assess potential synergistic interaction between tigecycline and aminoglycosides via in vitro and in vivo studies. METHODS: Antibiotic resistance profiles and molecular characteristics of 168 CR-KP clinical isolates were investigated by susceptibility testing, PCR and MLST. Chequerboard tests and time-kill assays were performed for 20 CR-KP isolates to evaluate in vitro synergistic effects of tigecycline combined with aminoglycosides. A tissue-cage infection model of rats was established to evaluate in vivo synergistic effects. Different doses of tigecycline and aminoglycosides alone or in combination were administered for 7 days via tail vein injection. Antibiotic efficacy was evaluated in tissue-cage fluid and emergence of resistance was screened. RESULTS: The chequerboard tests showed that this combination displayed synergistic or partial synergistic activity against CR-KP. The time-kill assays further demonstrated that strong synergistic effects of such a combination existed against isolates that were susceptible to both drugs but for resistant isolates no synergy was observed if clinical pharmacokinetics were taken into consideration. The in vivo study showed that the therapeutic effectiveness of combination therapies was better than that of monotherapy for susceptible isolates, suggesting in vivo synergistic effects. Furthermore, combinations of tigecycline with an aminoglycoside showed significant activity in reducing the occurrence of tigecycline-resistant mutants. CONCLUSIONS: Compared with single drugs, tigecycline combined with aminoglycosides could exert synergistic effects and reduce the emergence of tigecycline resistance. Such a combination might be an effective alternative when treating CR-KP infections in clinical practice.

Identification of hub genes and key pathways in the emphysema phenotype of COPD.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous condition associated with high morbidity and mortality. This study aimed to use weighted gene co-expression network analysis (WGCNA) to explore the molecular pathogenesis of the emphysema phenotype of COPD. After obtaining lung mRNA expression profiles from ten patients with the emphysema phenotype of COPD and eight controls, emphysema-associated gene modules were identified with WGCNA. Among 13 distinct modules, the green-yellow and brown modules showed the strongest correlations with emphysema severity and lung function and were thus selected as hub modules. On gene ontology analysis, these two modules were mainly enriched in immune response, B cell receptor (BCR) signaling pathway, extracellular matrix (ECM) organization, and collagen fibril organization. Pathway analysis primarily showed enrichment in BCR signaling pathways, ECM receptor interaction, and NF-κB and TGF-ß signaling pathways for the two hub modules. Several genes, including FCRLA, MS4A1, CD19, FKBP10, C1S and HTRA1, among others, were identified as hub genes. Our results shed light on the potential genetic mechanisms underlying the pathogenesis of the emphysema phenotype of COPD. However, further research will be needed to confirm the involvement of the identified genes and to determine their therapeutic relevance.

Mitoquinone ameliorates cigarette smoke-induced airway inflammation and mucus hypersecretion in mice.

BACKGROUND: Cigarette smoking, which induces airway inflammation and mucus hypersecretion, is a major risk factor for the development of cigarette smoke (CS)-induced airway disorders. In this study, we investigated the effects and mechanisms of mitoquinone (MitoQ), a mitochondria-targeted antioxidant, on CS-induced airway inflammation and mucus hypersecretion in mice. METHODS: C57BL/6J mice were exposed to CS for 75 min twice daily, 5 days per week for 4 weeks. MitoQ (2.5, 5 mg/kg/day) was administered intraperitoneally 1 h before CS exposure. Bronchoalveolar lavage fluid (BALF) was obtained for cell counting and determination of pro-inflammatory cytokine levels. Lung tissue was collected for histological examination; Western blotting was used to measure levels of Mfn2, Drp1, cytochrome c, NF-κB p65, and IκBα. RESULTS: Pretreatment with MitoQ significantly attenuated CS-induced thickening of the airway epithelium, peribronchial inflammatory cell infiltration, goblet cell hyperplasia and Muc5ac staining. The numbers of total cells, neutrophils and macrophages, as well as levels of TNF-α and IL-6 in BALF were remarkably decreased by MitoQ in a dose-dependent manner. MitoQ attenuated oxidative stress by preventing the CS-induced increase in malondialdehyde level and decrease in superoxide dismutase activity and GSH/GSSG ratio. MitoQ decreased the expression of mitochondrial fission protein Drp1 and increased that of mitochondrial fusion protein Mfn2, as well as reduced cytochrome c release into the cytosol. Furthermore, MitoQ suppressed IκBα degradation and NF-κB p65 nuclear translocation. CONCLUSIONS: MitoQ attenuates inflammation, mucus hypersecretion, and oxidative stress induced by CS. It may exert these effects in part by modulating mitochondrial function and the NF-κB signal pathway.

Role of angiotensin-converting enzyme 2 (ACE2) in COVID-19.

An outbreak of pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that started in Wuhan, China, at the end of 2019 has become a global pandemic. Both SARS-CoV-2 and SARS-CoV enter host cells via the angiotensin-converting enzyme 2 (ACE2) receptor, which is expressed in various human organs. We have reviewed previously published studies on SARS and recent studies on SARS-CoV-2 infection, named coronavirus disease 2019 (COVID-19) by the World Health Organization (WHO), confirming that many other organs besides the lungs are vulnerable to the virus. ACE2 catalyzes angiotensin II conversion to angiotensin-(1-7), and the ACE2/angiotensin-(1-7)/MAS axis counteracts the negative effects of the renin-angiotensin system (RAS), which plays important roles in maintaining the physiological and pathophysiological balance of the body. In addition to the direct viral effects and inflammatory and immune factors associated with COVID-19 pathogenesis, ACE2 downregulation and the imbalance between the RAS and ACE2/angiotensin-(1-7)/MAS after infection may also contribute to multiple organ injury in COVID-19. The SARS-CoV-2 spike glycoprotein, which binds to ACE2, is a potential target for developing specific drugs, antibodies, and vaccines. Restoring the balance between the RAS and ACE2/angiotensin-(1-7)/MAS may help attenuate organ injuries. SARS-CoV-2 enters lung cells via the ACE2 receptor. The cell-free and macrophage-phagocytosed virus can spread to other organs and infect ACE2-expressing cells at local sites, causing multi-organ injury.

Design Method of Lightweight Metamaterials with Arbitrary Poisson's Ratio.

A heuristic approach to design lightweight metamaterials with novel configurations and arbitrary Poisson's ratio is studied by using the functional element topology optimization (FETO) method. Mathematical model of the optimization problem is established, where the minimization of the mass is set as the objective, then a series of metamaterials with Poisson's ratio ranging from -1.0 to +1.0 are designed by solving this model. The deformation resistance and vibration reduction performance of the novel metamaterials and conventional honeycomb are compared by numerical simulations. Specific stiffness analysis shows that the novel metamaterials are 5.6 to 21.0 times more resistant to deformation than that of the honeycomb, and frequency response shows about 60% improvement in vibration reduction performance. Finally, the lightweight effects of the novel metamaterials on deformation resistance and vibration reduction performance are analyzed, and further analysis reflects that the lightweight effects increase with the increase of the absolute value of the Poisson's ratio.