Abstract Background Epidemiological studies have demonstrated that periodontitis is an independent risk factor for chronic obstructive pulmonary disease (COPD). However, the mechanism underlying the ...association between these two diseases remains unclear. The lung microbiota shares similarities with the oral microbiota, and there is growing evidence to suggest that the lung microbiome could play a role in the pathogenesis of COPD. This study aimed to investigate whether periodontal pathogens could contribute to the pathogenesis of COPD in a mouse model. Methods We established mouse models with oral infection by typical periodontal pathogens, porphyromonas gingivalis (Pg group) or fusobacterium nucleatum (Fn group), over a three-month period. Mice that did not receive oral infection were set as the control group (C group). We assessed the level of alveolar bone resorption, lung function, and histological changes in the lungs of the mice. Additionally, we measured the levels of inflammatory factors and tissue damage associated factors in the lung tissues. Results Lung function indices, including airway resistance, peak inspiratory/expiratory flow and expiratory flow-50%, were significantly reduced in the Fn group compared to the C group. Additionally, histological examination revealed an increased number of inflammatory cells and bullae formation in the lung tissue sections of the Fn group. Meanwhile, levels of inflammatory factors such as IL-1β, IL-6, IFN-γ, and TNF-α, as well as tissue damage associated factors like matrix metalloproteinase-8 and neutrophil elastase, were significantly elevated in the lung tissue of the Fn group in comparison to the C group. The Pg group also showed similar but milder lung changes compared to the Fn group. Pg or Fn could be detected in the lungs of both oral infected groups. Conclusion The results indicated that oral periodontal pathogens infection could induce COPD-like lung changes in mice, and they may play a biological role in the association between periodontitis and COPD.
Population-density-dependent polymorphism is important in the biology of some agricultural pests. The oriental armyworm (
) is a lepidopteran pest (family Noctuidae). As the population density ...increases, its body color becomes darker, and the insect eats more and causes greater damage to crops. The molecular mechanisms underlying this phase change are not fully clear. Here, we used transcriptomic and metabolomic methods to study the effect of population density on the differentiation of second-day sixth instar
larvae. The transcriptomic analysis identified 1148 differentially expressed genes (DEGs) in gregarious-type (i.e., high-population-density) armyworms compared with solitary-type (low-population-density) armyworms; 481 and 667 genes were up- and downregulated, respectively. The metabolomic analysis identified 137 differentially accumulated metabolites (DAMs), including 59 upregulated and 78 downregulated. The analysis of DEGs and DAMs showed that activation of the insulin-like signaling pathway promotes the melanization of gregarious armyworms and accelerates the decomposition of saccharides, which promotes the gregarious type to take in more food. The gregarious type is more capable of digesting and absorbing proteins and decreases energy consumption by inhibiting transcription and translation processes. The phase change traits of the armyworm are thus attributable to plasticity of its energy metabolism. These data broaden our understanding of the molecular mechanisms of insect-density-dependent polymorphism.
The aim of this study is to investigate the correlation between periodontal disease and chronic obstructive pulmonary disease (COPD) from the perspective of gene regulation, as well as the ...inflammatory pathways involved.
Forty C57BL/6 mice were randomly divided into four groups: control group, chronic periodontitis (CP) group, COPD group, and CP&COPD group. Lung tissue samples were selected for messenger ribonucleic acid (mRNA) sequencing analysis, and differential genes were screened out. Gene enrichment analysis was carried out, and then crosstalk gene enrichment analysis was conducted to explore the pathogenesis related to periodontal disease and COPD.
Results of enrichment analysis showed that the differentially expressed genes (DEGs) in the CP group were concentrated in response to bacterial origin molecules. The DEGs in the COPD group gene were enriched in positive regulation of B cell activation. The DEGs in the CP&COPD group were concentrated in neutrophil extravasation and neutrophil migration. The mice in the three experimental groups had 19 crosstalk genes, five of which were key genes.
Lcn2, S100a8, S100a9, Irg1, Clec4d are potential crossover genes of periodontal disease and COPD. Lcn2, S100a8, S100a9 are correlated with neutrophils in both diseases. Irg1 and Clec4d may bind to receptors on the surface of lymphocytes to produce cytokines and activate inflammatory pathways, this requires further research.
Cytochrome P450 (CYP) is a group of important detoxification enzymes found in insects related to their resistance to insecticides. To elucidate the CYP6 family genes of P450, which are potentially ...related to imidacloprid resistance in
, the CYP6 cDNA sequences of
were studied. The transcriptome of
was constructed, and the CYP6 cDNA sequences of
were screened. Their relative expression levels in response to imidacloprid induction were examined through qRT-PCR, and the CYP6s with higher expression levels were used to study the detoxification of imidacloprid through RNA interference and a bioassay. Twelve CYP6s were obtained from the
transcriptome. These samples were named by the International P450 Nomenclature Committee and registered in GenBank. After 3, 6, 12, 24 and 48 h of induction with LC50 concentrations of imidacloprid, the relative expression levels of these CYP6s increased; the expression level of
experienced the highest increase, being more than 3-fold higher than that of those of the non-imidacloprid-induced CYP6s. After RNA interference for
, the relative expression level of
significantly decreased after 3, 6 and 12 h, while the corresponding P450 enzyme activity decreased after 12 and 24 h. The mortality of
due to imidacloprid treatment increased by 14.71% at 24 h.
might detoxify imidacloprid in
. This study provides a theoretical basis for the further study of the mechanism of action of CYP6s and potential new methods for improving insecticidal efficacy.
Trehalose is an important carbohydrate substance in insect hemolymph. Chitin is the main component of cuticle and peritrophic matrix in insects. Trehalase (Tre) catalyzes the decomposition of ...trehalose. Few studies of trehalase in lepidopteran insects have been conducted. Here, the functions of soluble Tre (Tre1) and membrane-bound Tre (Tre2) in the growth and development of
were investigated. We cloned and identified
and
cDNA sequences in
. Analysis expression revealed that
and
were highly expressed in midgut and integument, respectively. The expression of
and
was highest in the pupal stage. We used RNA interference (RNAi) to inhibit
expression in
larvae. Injection of ds
or ds
resulted in abnormal phenotypes and impeded normal molting. Silencing of
and
resulted in significant changes in the expression of genes in the trehalose and chitin metabolism pathways, significantly increased the trehalose and glycogen content, and significantly decreased MsTre1 and MsTre2 activity, the glucose content, and the chitin content in midgut and integument. Silencing of
slowed larval molting, and the new cuticle was significantly thinner. These results indicate that RNAi of
may be useful for control strategies against
.
Bispecific killer cells engagers (BiKEs) which can bind to natural killer (NK) cells through the activating receptor CD16A and guide them to cells expressing the HIV-1 envelope glycoprotein (Env) are ...a promising new weapon for elimination of infected cells and eradication of the virus. Here we report the design, generation and characterization of BiKEs which consist of CD16A binding human antibody domains fused through a flexible linker to an engineered one-domain soluble human CD4. In presence of cells expressing HIV-1 envelope glycoproteins (Envs), these BiKEs activated specifically CD16A-expressing Jurkat T cells, degranulated NK cells, induced cytokine production and killed Env-expressing cells. They also effectively mediated killing of chronically and acutely HIV-1 infected T cells by human peripheral blood mononuclear cells. The presumed ability of these CD4-based BiKEs to bind all HIV-1 isolates, their small size and fully human origin, combined with high efficacy suggest their potential for HIV-1 eradication.
Carboxylesterases are one of the three major types of detoxification enzyme in insects. In this study, we screened 12 full‐length carboxylesterase cDNA sequences from the oriental armyworm Mythimna ...separata; they were named MsCarE1–MsCarE12 and registered in GenBank with accession numbers MK440541–MK440552. Treatment of fourth instar larvae of M. separata with the LD50 of the insecticide chlorantraniliprole increased the expression levels of MsCarE3 and MsCarE4, while treatment with the LD50 of lambda‐cyhalothrin significantly increased the expression levels of MsCarE5 and MsCarE10. Spatiotemporal expression detection showed that MsCarE3, MsCarE4, MsCarE5, and MsCarE10 were expressed at different developmental stages and in different tissues of M. separata and their expression levels were different. Induction using a high dose of chlorantraniliprole resulted in lower expression of MsCarE3 and MsCarE4. LD50 of lambda‐cyhalothrin induced higher expression of MsCarE5 and MsCarE10, while LD70 induced higher MsCarE10 expression at 3, 6, and 12 h after treatment. RNA interference successfully inhibited the expression of MsCarE3, MsCarE4, MsCarE5, and MsCarE10, to different degrees at different time points. Silencing of MsCarE5, or MsCarE5 and MsCarE10 simultaneously changed carboxylesterase activity and increased the susceptibility of M. separata larvae to lambda‐cyhalothrin. This study provides a new method to increase the insect susceptibility to insecticide.
Research Highlights
Twelve carboxylesterase cDNA sequences named MsCarE1–MsCarE12 were identified from Mythimna separata.
Silence of MsCarE5, or MsCarE5and MsCarE10 simultaneously increased the insecticidal activity of lambda‐cyhalothrin on M. separatalarvae.
Objective
The aim of this study was to investigate the association between periodontitis and total serum cholesterol level in patients with type 2 diabetic nephropathy (T2DN).
Background
...Periodontitis is now recognized as the sixth complication of diabetes and can also affect other complications of diabetes, including nephropathy and coronary artery diseases. Studies have considered dyslipidemia as a risk factor for exacerbation of periodontitis.
Methods
A total of 119 T2DN patients with chronic periodontitis were included in this observational study. Participants were stratified into the Normal (serum total cholesterol <5.17 mmol/L, n = 89) and the Dyslipidemia groups (serum total cholesterol ≥5.17 mmol/L, n = 30). Participants completed a validated questionnaire that collected information on oral hygiene behaviors and knowledge of oral health and underwent a clinical oral examination. The number of remaining teeth, probing depth (PD), clinical attachment level (CAL), and bleeding index (BI) was recorded. Physical examination and laboratory tests (fasting plasma glucose, serum glycosylated hemoglobin (HbA1c), total cholesterol, high‐density lipoprotein‐cholesterol (HDL‐C), low‐density lipoprotein‐cholesterol (LDL‐C), triglyceride, and high‐sensitivity C‐reactive protein levels) were performed.
Results
Means of CAL and BI were significantly higher in the Dyslipidemia group compared with the Normal group. In the Dyslipidemia group, PD and percent of sites with PD ≥4 mm were positively correlated with urinary albumin/creatinine ratios; PD and percent of sites with PD ≥4 and PD ≥5 mm were positively correlated with HbA1c level; a number of remaining teeth were negatively correlated with serum LDL‐C level. After adjusting for age, gender, body mass index, smoking, FPG, and serum HbA1c and triglyceride levels, BI was found to be positively associated with dyslipidemia in T2DN patients with periodontitis.
Conclusion
T2DN patients with chronic periodontitis had a 2.355‐fold higher risk of developing dyslipidemia, implying an important relationship between periodontitis and blood lipid control among T2DN patients.
Glypican 3 (GPC3) is an oncofetal antigen involved in Wnt-dependent cell proliferation that is highly expressed in hepatocellular carcinoma (HCC). We investigated whether the functions of chimeric ...antigen receptors (CARs) that target GPC3 are affected by their antibody-binding properties.
We collected peripheral blood mononuclear cells from healthy donors and patients with HCC and used them to create CAR T cells, based on the humanized YP7 (hYP7) and HN3 antibodies, which have high affinities for the C-lobe and N-lobe of GPC3, respectively. NOD/SCID/IL-2Rgcnull (NSG) mice were given intraperitoneal injections of luciferase-expressing (Luc) Hep3B or HepG2 cells and after xenograft tumors formed, mice were given injections of saline or untransduced T cells (mock control), or CAR (HN3) T cells or CAR (hYP7) T cells. In other NOD/SCID/IL-2Rgcnull (NSG) mice, HepG2-Luc or Hep3B-Luc cells were injected into liver, and after orthotopic tumors formed, mice were given 1 injection of CAR (hYP7) T cells or CD19 CAR T cells (control). We developed droplet digital polymerase chain reaction and genome sequencing methods to analyze persistent CAR T cells in mice.
Injections of CAR (hYP7) T cells eliminated tumors in 66% of mice by week 3, whereas CAR (HN3) T cells did not reduce tumor burden. Mice given CAR (hYP7) T cells remained tumor free after re-challenge with additional Hep3B cells. The CAR T cells induced perforin- and granzyme-mediated apoptosis and reduced levels of active β-catenin in HCC cells. Mice injected with CAR (hYP7) T cells had persistent expansion of T cells and subsets of polyfunctional CAR T cells via antigen-induced selection. These T cells were observed in the tumor microenvironment and spleen for up to 7 weeks after CAR T-cell administration. Integration sites in pre-infusion CAR (HN3) and CAR (hYP7) T cells were randomly distributed, whereas integration into NUPL1 was detected in 3.9% of CAR (hYP7) T cells 5 weeks after injection into tumor-bearing mice and 18.1% of CAR (hYP7) T cells at week 7. There was no common site of integration in CAR (HN3) or CD19 CAR T cells from tumor-bearing mice.
In mice with xenograft or orthoptic liver tumors, CAR (hYP7) T cells eliminate GPC3-positive HCC cells, possibly by inducing perforin- and granzyme-mediated apoptosis or reducing Wnt signaling in tumor cells. GPC3-targeted CAR T cells might be developed for treatment of patients with HCC.
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Object
To review recent advances of artificial intelligence (AI) in enhancing the efficiency and throughput of the MRI acquisition workflow in neuroimaging, including planning, sequence design, and ...correction of acquisition artifacts.
Materials and Methods
A comprehensive analysis was conducted on recent AI-based methods in neuro MRI acquisition. The study focused on key technological advances, their impact on clinical practice, and potential risks associated with these methods.
Results
The findings indicate that AI-based algorithms have a substantial positive impact on the MRI acquisition process, improving both efficiency and throughput. Specific algorithms were identified as particularly effective in optimizing acquisition steps, with reported improvements in workflow efficiency.
Discussion
The review highlights the transformative potential of AI in neuro MRI acquisition, emphasizing the technological advances and clinical benefits. However, it also discusses potential risks and challenges, suggesting areas for future research to mitigate these concerns and further enhance AI integration in MRI acquisition.
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