The role of the Notch signaling pathway in bacterial infectious diseases.

The Notch signaling pathway is the most crucial link in the normal operation and maintenance of physiological functions of mammalian life processes. Notch receptors interact with ligands and this leads to three cleavages and goes on to enter the nucleus to initiate the transcription of target genes. The Notch signaling pathway deeply participates in the differentiation and function of various cells, including immune cells. Recent studies indicate that the outcomes of Notch signaling are changeable and highly dependent on different bacterial infection. The Notch signaling pathway plays a different role in promoting and inhibiting bacterial infection. In this review, we focus on the latest research findings of the Notch signaling pathway in bacterial infectious diseases. The Notch signaling pathway is critically involved in a variety of development processes of immunosuppression of different APCs. The Notch signaling pathway leads to functional changes in epithelial cells to aggravate tissue damage. Specifically, we illustrate the regulatory mechanism of the Notch signaling pathway in various bacterial infections, such as Mycobacterium tuberculosis, Mycobacterium avium paratuberculosis, Mycobacterium leprae, Helicobacter pylori, Klebsiella pneumoniae, Bacillus subtilis, Staphylococcus aureus, Ehrlichia chaffeensis and sepsis. Collectively, this review will not only help beginners intuitively and systematically understand the Notch signaling pathway in bacterial infectious diseases but also help experts to generate fresh insight in this field.

Lipoprotein (a)-Related Inflammatory Imbalance: A Novel Horizon for the Development of Atherosclerosis.

PURPOSE OF REVIEW: The primary objective of this review is to explore the pathophysiological roles and clinical implications of lipoprotein(a) [Lp(a)] in the context of atherosclerotic cardiovascular disease (ASCVD). We seek to understand how Lp(a) contributes to inflammation and arteriosclerosis, aiming to provide new insights into the mechanisms of ASCVD progression. RECENT FINDINGS: Recent research highlights Lp(a) as an independent risk factor for ASCVD. Studies show that Lp(a) not only promotes the inflammatory processes but also interacts with various cellular components, leading to endothelial dysfunction and smooth muscle cell proliferation. The dual role of Lp(a) in both instigating and, under certain conditions, mitigating inflammation is particularly noteworthy. This review finds that Lp(a) plays a complex role in the development of ASCVD through its involvement in inflammatory pathways. The interplay between Lp(a) levels and inflammatory responses highlights its potential as a target for therapeutic intervention. These insights could pave the way for novel approaches in managing and preventing ASCVD, urging further investigation into Lp(a) as a therapeutic target.

Impact of baseline and trajectory of the atherogenic index of plasma on incident diabetic kidney disease and retinopathy in participants with type 2 diabetes: a longitudinal cohort study.

BACKGROUND: Some studies have assessed the predictive role of the atherogenic index of plasma (AIP) for macrovascular diseases. This prospective investigation aimed to elucidate whether AIP is associated with diabetic kidney disease (DKD) and diabetic retinopathy (DR) incidence. METHODS: The data were extracted from 4831 participants, of whom 2943 and 3360 participants with type 2 diabetes (T2D) were included in the DKD and DR follow-up analyses, respectively. Cox regression models were performed to test the relationships of AIP value at baseline with the risk of incident DKD and DR. Group-based trajectory modelling was utilized to discern AIP trajectories during the follow-up period. Subsequently, logistic regressions were applied to ascertain the influence of AIP trajectories on the incidence of DKD and DR. RESULTS: During the follow-up period, 709 (24.1%) and 193 (5.7%) participants developed DKD and DR, respectively. The median (interquartile range) follow-up time was 24.2 (26.3) months for DKD and 25.7 (27.0) months for DR. According to the multivariate Cox regression models, baseline AIP was positively and linearly related to the occurrence of DKD, with a hazard ratio of 1.75 (95% confidence interval [CI] 1.36-2.26). Three distinct trajectories of AIP were identified throughout the follow-up time: Low (31.4%), Median (50.2%), and High (18.3%). Compared to participants with the Low AIP trajectory, those with High and Median AIP trajectories presented 117% (95% CI: 1.62-2.91) and 84% (95% CI 1.46-2.32) greater odds of developing DKD, respectively. However, neither baseline levels nor trajectories of AIP were shown to be related to DR after adjusting for confounding factors. CONCLUSIONS: Baseline levels and trajectories of AIP were independently related to elevated DKD risk, indicating that AIP could be used as a predictor for identifying T2D participants at higher risk of DKD. No association between AIP and DR was detected.

Genome-scale top-down strategy to generate viable genome-reduced phages.

Efforts have been made to reduce the genomes of living cells, but phage genome reduction remains challenging. It is of great interest to investigate whether genome reduction can make phages obtain new infectious properties. We developed a CRISPR/Cas9-based iterative phage genome reduction (CiPGr) approach and applied this to four distinct phages, thereby obtaining heterogeneous genome-reduced mutants. We isolated and sequenced 200 mutants with loss of up to 8-23% (3.3-35 kbp) of the original sequences. This allowed the identification of non-essential genes for phage propagation, although loss of these genes is mostly detrimental to phage fitness to various degrees. Notwithstanding this, mutants with higher infectious efficiency than their parental strains were characterized, indicating a trade-off between genome reduction and infectious fitness for phages. In conclusion, this study provides a foundation for future work to leverage the information generated by CiPGr in phage synthetic biology research.

HMOX1 Participates in Pre-Eclampsia by Regulating the Proliferation, Apoptosis, and Angiogenesis Modulation Potential of Mesenchymal Stem Cells via VEGF.

Mesenchymal stem cells (MSCs) are involved in the pathogenesis of pre-eclampsia (PE). Heme oxygenase (HMOX) protects against placental cytotoxic injuries associated with PE. Here, we aimed to clarify the roles of HMOX1 in MSC proliferation and apoptosis, trophoblast cell migration, and regulation of angiogenesis, and assess its involvement in the pathogenesis of PE. HMOX1 and vascular endothelial growth factor (VEGF) expression levels in decidual tissues and decidua-derived MSCs (dMSCs) of healthy pregnant women and patients with PE were evaluated via quantitative reverse transcription-polymerase chain reaction and western blotting. Moreover, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, flow cytometry, and transwell assays were used to analyze the cell viability, apoptosis, and migration, respectively. The tube formation ability of human umbilical vein endothelial cells (HUVECs) was also evaluated. Compared to the healthy pregnant women, HMOX1 expression was upregulated in the decidual tissue and downregulated in the dMSCs of patients with PE. HMOX1 overexpression significantly increased dMSC proliferation, decreased cell apoptosis, and increased VEGF expression. Moreover, HMOX1-plasmid transfected dMSC culture supernatant promoted the migration of HTR-8/SVneo cells and improved angiogenesis by HUVECs. The opposite effects were observed in HMOX1-small interfering RNA-treated dMSCs cells. However, VEGF-siRNA reversed the effects of HMOX1-plasmid. HMOX1 is involved in the pathogenesis of PE by regulating the proliferation, apoptosis, and angiogenesis modulation potential of MSCs via VEGF, acting as a potential therapeutic target for PE.

Application of hyperbaric oxygen therapy in diabetic foot ulcers: A meta-analysis.

Hyperbaric oxygen therapy (HBOT) has been used in patients with diabetic foot ulcers (DFU) for many years, but its clinical efficacy is still controversial. Therefore, this study explored the efficacy of HBOT applied to DFU by means of meta-analysis. PubMed, Cochrane Library, Embase, CNKI and Wanfang databases were searched, from database inception to October 2023, and published randomised controlled trials (RCTs) of HBOT in DFU were collected. Two investigators independently screened the collected literature, extracted relevant data and assessed the quality of the literature. Review Manager 5.4 software was applied for data analysis. Twenty-nine RCTs with 1764 patients were included. According to the combined results, when compared with conventional treatment, HBOT significantly increased the complete healing rate of DFUs (46.76% vs. 24.46%, odds ratio [OR]: 2.83, 95% CI: 2.29-3.51, p < 0.00001) and decreased the amputation rate (26.03% vs. 45.00%, OR: 0.41, 95% CI: 0.18-0.95, p = 0.04), but the incidence of adverse events was significantly higher in patients (17.37% vs. 8.27%, OR: 2.49, 95% CI: 1.35-4.57, p = 0.003), whereas there was no significant difference in the mortality (6.96% vs. 12.71%, OR: 0.52, 95% CI: 0.21-1.28, p = 0.16). Our results suggest that HBOT is effective in increasing the complete healing rate and decreasing the amputation rate in patients with DFUs, but increases the incidence of adverse events, while it has no significant effect on mortality.

Histone acetyltransferase P300 deficiency promotes ferroptosis of vascular smooth muscle cells by activating the HIF-1α/HMOX1 axis.

BACKGROUND: E1A-associated 300-kDa protein (P300), an endogenous histone acetyltransferase, contributes to modifications of the chromatin landscape of genes involved in multiple cardiovascular diseases. Ferroptosis of vascular smooth muscle cells (VSMCs) is a novel pathological mechanism of aortic dissection. However, whether P300 regulates VSMC ferroptosis remains unknown. METHODS: Cystine deprivation (CD) and imidazole ketone erastin (IKE) were used to induce VSMC ferroptosis. Two different knockdown plasmids targeting P300 and A-485 (a specific inhibitor of P300) were used to investigate the function of P300 in the ferroptosis of human aortic smooth muscle cells (HASMCs). Cell counting kit-8, lactate dehydrogenase and flow cytometry with propidium iodide staining were performed to assess the cell viability and death under the treatment of CD and IKE. BODIPY-C11 assay, immunofluorescence staining of 4-hydroxynonenal and malondialdehyde assay were conducted to detect the level of lipid peroxidation. Furthermore, co-immunoprecipitation was utilized to explore the interaction between P300 and HIF-1α, HIF-1α and P53. RESULTS: Compared with normal control, the protein level of P300 was significantly decreased in HASMCs treated with CD and IKE, which was largely nullified by the ferroptosis inhibitor ferrostatin-1 but not by the autophagy inhibitor or apoptosis inhibitor. Knockdown of P300 by short-hairpin RNA or inhibition of P300 activity by A-485 promoted CD- and IKE-induced HASMC ferroptosis, as evidenced by a reduction in cell viability and aggravation of lipid peroxidation of HASMCs. Furthermore, we found that hypoxia-inducible factor-1α (HIF-1α)/heme oxygenase 1 (HMOX1) pathway was responsible for the impacts of P300 on ferroptosis of HASMCs. The results of co-immunoprecipitation demonstrated that P300 and P53 competitively bound HIF-1α to regulate the expression of HMOX1. Under normal conditions, P300 interacted with HIF-1α to inhibit HMOX1 expression, while reduced expression of P300 induced by ferroptosis inducers would favor HIF-1α binding to P53 to trigger HMOX1 overexpression. Furthermore, the aggravated effects of P300 knockdown on HASMC ferroptosis were largely nullified by HIF-1α knockdown or the HIF-1α inhibitor BAY87-2243. CONCLUSION: Thus, our results revealed that P300 deficiency or inactivation facilitated CD- and IKE-induced VSMC ferroptosis by activating the HIF-1α/HMOX1 axis, which may contribute to the development of diseases related to VSMC ferroptosis.

A Glycosylated RBD Protein Induces Enhanced Neutralizing Antibodies against Omicron and Other Variants with Improved Protection against SARS-CoV-2 Infection.

SARS-CoV-2 has mutated frequently since its first emergence in 2019. Numerous variants, including the currently emerging Omicron variant, have demonstrated high transmissibility or increased disease severity, posing serious threats to global public health. This study describes the identification of an immunodominant non-neutralizing epitope on SARS-CoV-2 receptor-binding domain (RBD). A subunit vaccine against this mutant RBD, constructed by masking this epitope with a glycan probe, did not significantly affect RBD's receptor-binding affinity or antibody-binding affinity, or its ability to induce antibody production. However, this vaccine enhanced the neutralizing activity of this RBD and its protective efficacy in immunized mice. Specifically, this vaccine elicited significantly higher-titer neutralizing antibodies than the prototypic RBD protein against Alpha (B.1.1.7 lineage), Beta (B.1.351 lineage), Gamma (P.1 lineage), and Epsilon (B.1.427 or B.1.429 lineage) variant pseudoviruses containing single or combined mutations in the spike (S) protein, albeit the neutralizing antibody titers against some variants were slightly lower than against original SARS-CoV-2. This vaccine also significantly improved the neutralizing activity of the prototypic RBD against pseudotyped and authentic Delta (B.1.617.2 lineage) and Omicron (B.1.1.529 lineage) variants, although the neutralizing antibody titers were lower than against original SARS-CoV-2. In contrast to the prototypic RBD, the mutant RBD completely protected human ACE2 (hACE2)-transgenic mice from lethal challenge with a prototype SARS-CoV-2 strain and a Delta variant without weight loss. Overall, these findings indicate that this RBD vaccine has broad-spectrum activity against multiple SARS-CoV-2 variants, as well as the potential to be effective and have improved efficacy against Omicron and other pandemic variants. IMPORTANCE Several SARS-CoV-2 variants have shown increased transmissibility, calling for a need to develop effective vaccines with broadly neutralizing activity against multiple variants. This study identified a non-neutralizing epitope on the receptor-binding domain (RBD) of SARS-CoV-2 spike protein, and further shielded it with a glycan probe. A subunit vaccine based on this mutant RBD significantly enhanced the ability of prototypic RBD against multiple SARS-CoV-2 variants, including the Delta and Omicron strains, although the neutralizing antibody titers against some of these variants were lower than those against original SARS-CoV-2. This mutant vaccine also enhanced the protective efficacy of the prototypic RBD vaccine against SARS-CoV-2 infection in immunized animals. In conclusion, this study identified an engineered RBD vaccine against Omicron and other SARS-CoV-2 variants that induced stronger neutralizing antibodies and protection than the original RBD vaccine. It also highlights the need to improve the effectiveness of current COVID-19 vaccines to prevent pandemic SARS-CoV-2 variants.

Novel virus-like nanoparticle vaccine effectively protects animal model from SARS-CoV-2 infection.

The key to battling the COVID-19 pandemic and its potential aftermath is to develop a variety of vaccines that are efficacious and safe, elicit lasting immunity, and cover a range of SARS-CoV-2 variants. Recombinant viral receptor-binding domains (RBDs) are safe vaccine candidates but often have limited efficacy due to the lack of virus-like immunogen display pattern. Here we have developed a novel virus-like nanoparticle (VLP) vaccine that displays 120 copies of SARS-CoV-2 RBD on its surface. This VLP-RBD vaccine mimics virus-based vaccines in immunogen display, which boosts its efficacy, while maintaining the safety of protein-based subunit vaccines. Compared to the RBD vaccine, the VLP-RBD vaccine induced five times more neutralizing antibodies in mice that efficiently blocked SARS-CoV-2 from attaching to its host receptor and potently neutralized the cell entry of variant SARS-CoV-2 strains, SARS-CoV-1, and SARS-CoV-1-related bat coronavirus. These neutralizing immune responses induced by the VLP-RBD vaccine did not wane during the two-month study period. Furthermore, the VLP-RBD vaccine effectively protected mice from SARS-CoV-2 challenge, dramatically reducing the development of clinical signs and pathological changes in immunized mice. The VLP-RBD vaccine provides one potentially effective solution to controlling the spread of SARS-CoV-2.

Phosphorylation of androgen receptor by mTORC1 promotes liver steatosis and tumorigenesis.

BACKGROUND AND AIMS: Androgen receptor (AR) has been reported to play an important role in the development and progression of man's prostate cancer. Hepatocellular carcinoma (HCC) is also male-dominant, but the role of AR in HCC remains poorly understood. Mechanistic target of rapamycin complex 1 (mTORC1) also has been reported to be highly activated in HCC. In this study, we aimed to explore the role of AR phosphorylation and its relationship with mTORC1 in hepatocarcinogenesis. APPROACH AND RESULTS: In vitro experiment, we observed that mTORC1 interacts with hepatic AR and phosphorylates it at S96 in response to nutrient and mitogenic stimuli in HCC cells. S96 phosphorylation promotes the stability, nuclear localization, and transcriptional activity of AR, which enhances de novo lipogenesis and proliferation in hepatocytes and induces liver steatosis and hepatocarcinogenesis in mice independently and cooperatively with androgen. Furthermore, high ARS96 phosphorylation is observed in human liver steatotic and HCC tissues and is associated with overall survival and disease-free survival, which has been proven as an independent survival predictor for patients with HCC. CONCLUSIONS: AR S96 phosphorylation by mTORC1 drives liver steatosis and HCC development and progression independently and cooperatively with androgen, which not only explains why HCC is man-biased but also provides a target molecule for prevention and treatment of HCC and a potential survival predictor in patients with HCC.

Visit-to-visit HbA1c variability is associated with aortic stiffness progression in participants with type 2 diabetes.

BACKGROUND: Glycemic variability plays an important role in the development of cardiovascular disease (CVD). This study aims to determine whether long-term visit-to-visit glycemic variability is associated with aortic stiffness progression in participants with type 2 diabetes (T2D). METHODS: Prospective data were obtained from 2115 T2D participants in the National Metabolic Management Center (MMC) from June 2017 to December 2022. Two brachial-ankle pulse wave velocity (ba-PWV) measurements were performed to assess aortic stiffness over a mean follow-up period of 2.6 years. A multivariate latent class growth mixed model was applied to identify trajectories of blood glucose. Logistic regression models were used to determine the odds ratio (OR) for aortic stiffness associated with glycemic variability evaluated by the coefficient of variation (CV), variability independent of the mean (VIM), average real variability (ARV), and successive variation (SV) of blood glucose. RESULTS: Four distinct trajectories of glycated hemoglobin (HbA1c) or fasting blood glucose (FBG) were identified. In the U-shape class of HbA1c and FBG, the adjusted ORs were 2.17 and 1.21 for having increased/persistently high ba-PWV, respectively. Additionally, HbA1c variability (CV, VIM, SV) was significantly associated with aortic stiffness progression, with ORs ranging from 1.20 to 1.24. Cross-tabulation analysis indicated that the third tertile of the HbA1c mean and VIM conferred a 78% (95% confidence interval [CI] 1.23-2.58) higher odds of aortic stiffness progression. Sensitivity analysis demonstrated that the SD of HbA1c and the highest HbA1c variability score (HVS) were significantly associated with the adverse outcomes independent of the mean of HbA1c during the follow-up. CONCLUSIONS: Long-term visit-to-visit HbA1c variability was independently associated with aortic stiffness progression, suggesting that HbA1c variability was a strong predictor of subclinical atherosclerosis in T2D participants.

Fabrication of Nitrogen-Doped Carbon-Coated NiS1.97 Quantum Dots for Advanced Magnesium-Ion Batteries.

Magnesium (Mg) batteries have garnered considerable interest because of their safety characteristics and low costs. However, the practical application of Mg batteries is hindered by the slow diffusion of Mg ions in the cathode materials. In this study, we prepared NiS1.97 quantum dot composites with nitrogen doping and carbon coating (NiS1.97 QDs@NC) using a one-step sulfurization process with NiO QDs/Ni@NC as the precursor. We applied the prepared NiS1.97 QDs/Ni@NC-based cathodes to Mg batteries because of the large surface area of the quantum dot composite, which provided abundant intercalation sites. This design ensured efficient deintercalation of magnesium ions during charge-discharge processes. The fabricated NiS1.97 QDs@NC displayed a high reversible Mg storage capacity of 259.1 mAh g-1 at 100 mA g-1 and a good rate performance of 96.0 mAh g-1 at 1000 mA g-1. Quantum dot composites with large surface areas provide numerous embedded sites, which ensure effective deintercalation of Mg ions during cycling. Thus, the proposed cathode synthesis strategy is promising for Mg-ion-based energy storage systems.

Risk factors for cognitive dysfunction and glycemic management in older adults with type 2 diabetes mellitus: a retrospective study.

BACKGROUND: Epidemiological evidence shows a robust relationship between cognitive dysfunction and type 2 diabetes mellitus (T2DM). This study identified major risk factors that might prevent or ameliorate T2DM-associated cognitive dysfunction in the realm of clinical practice. METHODS: Using Mini-mental State Examination (MMSE) in the light of education level, we identified older adults with T2DM on admission aged 50 and above. We conducted this case-control study when eligible participants were divided into Cognitively Normal (CN) group and Cognitively Impaired (CI) group. Analytical data referred to demographic characteristics, clinical features, fluid biomarkers, and scale tests. RESULTS: Of 596 records screened, 504 cases were included in the final analysis. Modified multivariate logistic regression analysis verified that homocysteine (OR = 2.048, 95%CI = 1.129-3.713), brain infarction (OR = 1.963, 95%CI = 1.197-3.218), dementia (OR = 9.430, 95%CI = 2.113-42.093), education level (OR = 0.605, 95%CI = 0.367-0.997), severity of dependence (OR = 1.996, 95%CI = 1.397-2.851), creatine kinase (OR = 0.514, 95%CI = 0.271-0.974) were significant risk factors of incident T2DM-related cognitive dysfunction in patients of advanced age. CONCLUSION: Our study supported a robust relationship between T2DM and cognitive dysfunction. Our results provide clinicians with major risk factors for T2DM-related cognitive dysfunction, in particular the protective role of creatine kinase.

Isolation and identification of hemostatic steroidal glycosides from Ypsilandra thibetica.

The phytoconstituents of the fraction with hemostatic activity of the 70% aqueous ethanol extract of Ypsilandra thibetica Franch. were investigated. As a result, fourteen previously unreported spirostanol saponins, ypsilandrosides Z1-Z14, and nine known analogues were isolated and characterized by MS, NMR, and chemical methods. Among them, ypsilandrosides Z1-Z4 (1-4) have a rare 12-O-ß-d-glucopyranosyl group, while ypsilandrosides Z5-Z8 (5-8) possess a rare double bond between C-4 and C-5, and a hydroxyl or carbonyl located at the C-6. All isolates were further tested for their hemostatic activity. The results suggested that five spirostanol tetraglycosides show favorable inducing platelet aggregation activities. Among them, ypsilandroside G (16) displayed significant inducing platelet aggregation activity with an EC50 value of 57.17 µM. Furthermore, the preliminary structure-activity relationship of these spirostanol glycosides' hemostatic activity was discussed.

Design, synthesis and biological activity of novel triketone herbicides containing natural product fragments.

4-Hydroxyphenylpyruvate dioxygenase (EC 1.13.11.27, HPPD) belongs to the non-heme Fe2+ - containing enzyme family and is an important enzyme in tyrosine decomposition. HPPD is crucial to the discovery of novel bleaching herbicides. To develop novel HPPD inhibitor herbicides containing the ß-triketone motif, a series of 4-hydroxyl-3-(substituted aryl)-pyran-2-one derivatives were designed using the active fragment splicing method. The title compounds were synthesized and characterized through infrared spectroscopy (IR), 1H nuclear magnetic resonance (1H NMR), 13C nuclear magnetic resonance (13C NMR), and high-resolution mass spectrometry (HRMS). The X-ray diffraction method determined the single crystal structure of I-17. Preliminary bioassay data revealed that several novel compounds, especially I-12 and II-3, showed excellent herbicidal activity against broadleaf and monocotyledonous weeds at a dose of 150 g ai/ha. The results of crop selectivity and carotenoids determination indicated that compound I-12 is more suitable for wheat and cotton fields than mesotrione. Additionally, compound II-3 is safer for soybeans and peanuts than mesotrione. The inhibitory activity of Arabidopsis thaliana HPPD (AtHPPD) verified that compound II-3 showed the most activity with an IC50 value of 0.248 µM, which was superior to that of mesotrione (0.283 µM) in vitro. The binding mode of compound II-3 and AtHPPD was confirmed through molecular docking and molecular dynamics simulations. This study provides insights into the future development of natural and efficient herbicides.

Extracellular Vesicles Released from Macrophages Infected with Mycoplasma pneumoniae Stimulate Proinflammatory Response via the TLR2-NF-κB/JNK Signaling Pathway.

Mycoplasma pneumoniae (M. pneumoniae, Mp) is an intracellular pathogen that causes pneumonia, tracheobronchitis, pharyngitis, and asthma in humans and can infect and survive in the host cells leading to excessive immune responses. Extracellular vesicles (EVs) from host cells carry components of pathogens to recipient cells and play a role in intercellular communication during infection. However, there is limited knowledge on whether EVs derived from M. pneumoniae-infected macrophages play as intercellular messengers and functional mechanisms. In this study, we establish a cell model of M. pneumoniae-infected macrophages that continuously secrete EVs to further asses their role as intercellular messengers and their functional mechanisms. Based on this model, we determined a method for isolating the pure EVs from M. pneumoniae-infected macrophages, which employs a sequence of operations, including differential centrifugation, filtering, and ultracentrifugation. We identified EVs and their purity using multiple methods, including electron microscopy, nanoparticle tracking analysis, Western blot, bacteria culture, and nucleic acid detection. EVs from M. pneumoniae-infected macrophages are pure, with a 30-200 nm diameter. These EVs can be taken up by uninfected macrophages and induce the production of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, and IL-8 through the nuclear factor (NF)-κB, and mitogen-activated protein kinases (MAPK) signals pathway. Moreover, the expression of inflammatory cytokines induced by EVs relies on TLR2-NF-κB/JNK signal pathways. These findings will help us better understand a persistent inflammatory response and cell-to-cell immune modulation in the context of M. pneumoniae infection.

Integrating biogeographic approach into classical biological control: Assessing the climate matching and ecological niche overlap of two natural enemies against common ragweed in China.

Plant invasion is considered a high priority threat to biodiversity, ecosystems, the environment, and human health worldwide. Classical biological control (biocontrol) is a generally safer and more environmentally benign measure than chemical controls in managing invasive alien plants (IAPs). However, the impacts of climate change and the importance of climate matching in ensuring the efficiency of biocontrol candidates in controlling IAPs are likely to be underestimated. Here, based on the ensemble model and n-dimensional hypervolumes concepts, we estimated the overlapping areas between Ambrosia artemisiifolia and its two most effective natural enemies (Ophraella communa and Epiblema strenuana) under climate change in China. Moreover, we compared their ecological niches, further assessing the impact of climate change on the efficiency of two natural enemies in controlling A. artemisiifolia in China. We found that the potentially suitable areas of the two natural enemies and A. artemisiifolia were primarily influenced by temperature and human influence index variables. Under near-current climate, the overlapping area between O. communa and A. artemisiifolia was the largest, followed by E. strenuana and A. artemisiifolia, and both two natural enemies and A. artemisiifolia. The ecological niche between A. artemisiifolia and O. communa was most similar (0.64), followed by A. artemisiifolia and E. strenuana (0.55). The separate control (the niche separation areas of the two natural enemies against A. artemisiifolia) and joint-control (the niche overlap areas of the two natural enemies against A. artemisiifolia) efficiencies of the two natural enemies against A. artemisiifolia will both increase in future climates (the 2030s and 2050s) in northern and northeastern China. Our findings demonstrate a new approach to assess control efficiency and screen potential release areas of two natural enemies against A. artemisiifolia in China without the need for actual field release or experimentation. Moreover, our findings provide important clues for ensuring the classical biocontrol of IAPs worldwide.

Photosensitive Dye as an Ideal Peroxymonosulfate Activator for Efficient Self-Degradation: A Novel Idea of Using Waste to Treat Waste.

Commonly used peroxydisulfate (PS) or peroxymonosulfate (PMS) activation methods have been limited in their practical application due to certain drawbacks, such as high cost, high energy consumption and secondary pollution. In this study, a catalyst-free alizarin green (AG) self-activating PMS catalytic system was constructed based on photosensitization properties of dye, which ultimately achieved efficient degradation of the dye activator, also the target pollutant. Here, 52.5% of the 100 mL mixture of 10 mg/L AG decomposed within 60 min with 1 mM PMS under visible-light irradiation, thereby showing a strong pH adaptation. Mechanism of AG self-activating PMS was revealed that the photo-excited AG can effectively transfer photo-induced electrons to PMS for its activation, which generates reactive oxidizing species dominated by singlet oxygen (1O2), and supplemented by hydroxyl radical (•OH), superoxide radical (O2•-) and sulfate radical (SO4•-) to realize the efficient self-degradation of the dye pollutants. Moreover, such self-catalytic system operated well under natural sunlight irradiation, indicating the great application potential in the actual wastewater treatment. Herein, photosensitive dye acted as an ideal PMS activator realizing its efficient self-degradation, which provides a novel idea of "using waste to treat waste" for developing wastewater treatment process in a high-efficiency and low-consumption way.

Identification of 4-hydroxyphenylpyruvate dioxygenase inhibitors by virtual screening, molecular docking, molecular dynamic simulation.

BACKGROUND: 4-Hydroxyphenylpyruvate dioxygenase (HPPD) herbicides control broadleaf and gramineous weeds with better crop safety for corn, sorghum and wheat. Multiple screening models in silico have been established to obtain novel lead compounds as HPPD inhibition herbicides. RESULTS: Topomer comparative molecular field analysis (CoMFA) combined with topomer search technology and Bayesian, genetic approximation functions (GFA) and multiple linear regression (MLR) models generated by calculating different descriptors were constructed for the quinazolindione derivatives of HPPD inhibitors. The coefficient of determination (r2 ) of topomer CoMFA, MLR and GFA were 0.975, 0.970 and 0.968, respectively; all the models established displayed excellent accuracy and high predictive capacity. Five compounds with potential HPPD inhibition were obtained via screening fragment library combined with the validation of the above models and molecular docking studies. After molecular dynamics (MD) validation and absorption, distribution, metabolism, excretion and toxicity (ADMET) prediction, the compound 2-(2-amino-4-(4H-1,2,4-triazol-4-yl) benzoyl)-3-hydroxycyclohex-2-en-1-one not only exhibited stable interactions with the protein but also high solubility and low toxicity, and has potential as a novel HPPD inhibition herbicide. CONCLUSION: In this study, five compounds were obtained through multiple quantitative structure-activity relationship screening. Molecular docking and MD experiments showed that the constructed approach had good screening ability for HPPD inhibitors. This work provided molecular structural information for developing novel, highly efficient and low-toxicity HPPD inhibitors. © 2023 Society of Chemical Industry.

Reference range of naïve T and T memory lymphocyte subsets in peripheral blood of healthy adult.

Naïve T and T memory cell subsets are closely related to immune response and can provide important information for the diagnosis and treatment of immunological and hematological disorders. Lymphocyte compartment undergoes dramatic changes during adulthood; age-related reference values derived from healthy individuals are crucial. However, extensively detailed reference values of peripheral blood lymphocytes in the whole spectrum of adulthood detected by multi-color flow cytometry on a single platform are rare. Three hundred and nine healthy adult volunteers were recruited from Tianjin in China. The absolute counts and percentages of CD3+CD4+ T cells, CD3+CD8+ T cells, naïve T cells (Tn), T memory stem cells (Tscm), central memory T cells (Tcm), effector memory T cells (Tem), and terminal effector T cells (Tte) were detected by flow cytometry with single platform technologies. Reference range of absolute counts and percentage of T lymphocyte subsets were formulated by different age and gender. The results showed that Tn and Tscm cells, which had stem cell properties, decreased with aging; while, Tcm and Tem increased with aging, which increased from 18 to 64 years old but presented no significant change over the 65 years old. Gender had an influence on the fluctuation of lymphocyte subsets, the absolute count of CD3+CD8+, CD8+Tcm, CD8+Tem in males were higher than those in females. The reference values of percentages and absolute numbers of naïve T and T memory cell subsets can help doctors to understand the immune state of patients and evaluate conditions of prognosis then adjust the treatment for patients. (Chinese Clinic Trial Registry number: ChiCTR-IOR-17014139.).