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Objective To establish and evaluate the clinical teaching and training model for refresher anesthesiologists. Methods A total of 25 refresher anesthesiologists from the Department of Anesthesiology in Peking Union Medical College Hospital during the period of March to September 2023 were enrolled. They were taught with the clinical teaching and training model, namely 'tutorial system-knowledge update-clinical practice'. The refresher anesthesiologists completed the same structured pre-designed questionnaire at the beginning and the end of training respectively. The scores were recorded and compared to evaluate the effectiveness of the clinical training model. Feedback from refresher anesthesiologists about the teaching and training model was also collected. Results Altogether 84%(21/25) and 100%(25/25) of questionnaires distributed were completed respectively, and 92% students gave positive feedback. The mean score at the end of training (10.1±1.1) was significantly higher than that at the beginning (5.6±1.8)(P < 0.01). Conclusion The 'tutorial system-knowledge update-clinical practice' clinical teaching and training model was significantly useful to elevate the effectiveness of training refresher anesthesiologists and their satisfaction.

Statins, the first‐line medication for dyslipidemia, are linked to an increased risk of type 2 diabetes. But exactly how statins cause diabetes is yet unknown. In this study, a developed short‐term statin therapy on hyperlipidemia mice show that hepatic insulin resistance is a cause of statin‐induced diabetes. Statin medication raises the expression of progesterone and adiponectin receptor 9 (PAQR9) in liver, which inhibits insulin signaling through degradation of protein phosphatase, Mg2+/Mn2+ dependent 1 (PPM1α) to activate ERK pathway. STIP1 homology and U‐box containing protein 1 (STUB1) is found to mediate ubiquitination of PPM1α promoted by PAQR9. On the other hand, decreased activity of hepatocyte nuclear factor 4 alpha (HNF4α) seems to be the cause of PAQR9 expression under statin therapy. The interventions on PAQR9, including deletion of PAQR9, caloric restriction and HNF4α activation, are all effective treatments for statin‐induced diabetes, while liver specific over‐expression of PPM1α is another possible tactic. The results reveal the importance of HNF4α‐PAQR9‐STUB1‐PPM1α axis in controlling the statin‐induced hepatic insulin resistance, offering a fresh insight into the molecular mechanisms underlying statin therapy. [ABSTRACT FROM AUTHOR]

This paper introduces an adaptive control scheme for quadrotor suspended load systems, to track desired trajectory with variable payload and wind disturbances. The dynamic model of the quadrotor suspended load system is developed, taking into account the impact of the wind field described by the Dryden model. To attenuate the effects of payload variation and wind disturbances on the system, an adaptive control method based on disturbance observers is devised. Additionally, the uniform boundedness of all error signals is demonstrated. The effectiveness of the designed control method is verified through simulations, which serves to strengthen its applicability in practical applications. [ABSTRACT FROM AUTHOR]

Mucosal immunity is the main defense line against respiratory disease pathogens. Newcastle disease and avian infectious bronchitis are common respiratory diseases in poultry. However, the mucosal immune response is not sufficiently activated and thus fails to achieve the ideal immune protection. Therefore, it is important to develop a suitable mucosal immune adjuvant to enhance the immune response of live vaccines. Here, the bursal-derived peptide BP7, β-glucan, and hyaluronic acid were selected as the adjuvant to be assembled into the composite nanopolypeptide adjuvant (CNPB7) with ultrasonic dispersion technology. The results showed that after optimizing assembly conditions, the optimal average particle size of nanoparticle CNPB7 was 514.9 nm and PDI was 0.298. To evaluate the non-specific immune responses of nanoparticle CNPB7, the chickens were immunized only with nanoparticle CNPB7. It was confirmed that nanoparticle CNPB7 enhanced the expression of CD3, CD4, CD80, and CD86 factors in the spleen lymphocyte from the chicken immunized with nanoparticle CNPB7. To investigate the mucosal immune response of nanoparticle CNPB7, the chickens were orally immunized with Newcastle disease virus (NDV)–infectious bronchitis virus (IBV) dual vaccines and CNPB7. The results proved that the levels of immunoglobulin SIgA, IL-4, IFN-γ, and IL-13 in the mucus samples from the respiratory and digestive tract in chicken immunized with nanoparticle CNPB7 and vaccines were significantly increased, compared to that of vaccine control. Finally, it was observed that nanoparticle CNPB7 promoted specific increased antibody productions against NDV and IBV in the immunized chicken. These results proved that the assembled nanoparticle CNPB7 could enhance the vaccination efficacy in chicken, which provided the experimental basis for the development of new adjuvants, and offered technical support for preventing virus transmission of avian diseases. [ABSTRACT FROM AUTHOR]

As a representative item of chemical carcinogen, MNNG is closely associated with the onset of gastric cancer (GC), where N6-methyladonosine (m6A) RNA methylation is recognized as a critical epigenetic event. In our previous study, we found that the m6A modification by methyltransferase METTL3 was up-regulated in MNNG-exposed malignant GES-1 cells (MC cells) compared to control cells in vitro, and long non-coding RNA SNHG7 as a downstream target of the METTL3. However, the functional role of METTL3 in mediating the SNHG7 axis in MNNG-induced GC remains unclear. In the present study, we continuously investigate the functional role of METTL3 in mediating the SNHG7 axis in MNNG-induced GC. RIP-PCR and m6A-IP-qPCR were used to examine the molecular mechanism underlying the METTL3/m6A/SNHG7 axis in MNNG-induced GC. A METTL3 knockout mice model was constructed and exposed by MNNG. Western blot analysis, IHC analysis, and RT-qPCR were used to measure the expression of METTL3, SNHG7, and EMT markers. In this study, we demonstrated that in MNNG-induced GC tumorigenesis, the m6A modification regulator METTL3 facilitates cellular EMT and biological functions through the m6A/SNHG7 axis using in vitro and in vivo models. In conclusion, our study provides novel insights into critical epigenetic molecular events vital to MNNG-induced gastric carcinogenesis. These findings suggest the potential therapeutic targets of METTL3 for GC treatment. [ABSTRACT FROM AUTHOR]

The fungal infection, cryptococcosis, is responsible for >100,000 deaths annually. No licensed vaccines are available. We explored the efficacy and immune responses of subunit cryptococcal vaccines adjuvanted with Cationic Adjuvant Formulation 01 (CAF01). CAF01 promotes humoral and T helper (Th) 1 and Th17 immune responses and has been safely used in human vaccine trials. Four subcutaneous vaccines, each containing single recombinant Cryptococcus neoformans protein antigens, partially protected mice from experimental cryptococcosis. Protection increased, up to 100%, in mice that received bivalent and quadrivalent vaccine formulations. Vaccinated mice that received a pulmonary challenge with C. neoformans had an influx of leukocytes into the lung including robust numbers of polyfunctional CD4+ T cells which produced Interferon gamma (IFNγ), tumor necrosis factor alpha (TNFα), and interleukin (IL)-17 upon ex vivo antigenic stimulation. Cytokine-producing lung CD8+ T cells were also found, albeit in lesser numbers. A significant, durable IFNγ response was observed in the lungs, spleen, and blood. Moreover, IFNγ secretion following ex vivo stimulation directly correlated with fungal control in the lungs. Thus, we have developed multivalent cryptococcal vaccines which protect mice from experimental cryptococcosis using an adjuvant which has been safely tested in humans. These preclinical studies suggest a path towards human cryptococcal vaccine trials. Author summary: Cryptococcosis is a fungal infection that poses great challenges to public health, especially in resource-limited regions with high HIV prevalence. Despite the urgent need, no licensed vaccines are currently available. In this study, we used a lethal mouse model of cryptococcosis to explore protection and immune responses elicited by vaccines consisting of recombinant cryptococcal proteins formulated with CAF01, an adjuvant that has an established safety and immunogenicity profile in human clinical vaccine trials. We discovered that while vaccines containing a single protein partially protected mouse strains, the protection was greatly augmented when the mice received vaccines formulated with multiple antigens. The lungs of vaccinated and infected mice had a robust influx of CD4+ T cells, many of which made the cytokines IFNγ and IL-17 when stimulated ex vivo. Moreover, we found the higher production of IFNγ directly correlated with better fungal control in the lungs. Cytotoxic CD8+ T cell responses were also observed, albeit in lesser numbers. Our promising findings from this preclinical research paves the way for future human cryptococcal vaccine trials. [ABSTRACT FROM AUTHOR]

Pigments play a pivotal role in the cosmetic industry, in which the development of pigments with concurrent color diversity, hydrophobicity, biocompatibility and photostability remains a great challenge. Herein, we report organic–inorganic composite pigments synthesized via a combination of organic dye anions (Ponceau SX and acid green (AG)), layered double hydroxides (LDHs) and octyltriethoxysilane (OTEOS) (denoted as O/Dye-LDHs: O/SX-LDHs and O/AG-LDHs).The prepared composite pigments were characterized via a comprehensive investigation based on X-ray diffraction (XRD), scanning electron microscopy (SEM), energy-dispersive spectroscopy (EDS-mapping), Fourier transform infrared (FT-IR) spectroscopy, CIE 1976 L*a*b* color scales, static contact angle measurement and HET-CAM assay. The results confirm the successful intercalation of organic dye anions into the interlayer region of LDHs via host–guest interactions and the surface modification of OTEOS on the layer surface, forming a new kind of hydrophobic organic–inorganic composite pigment with a sandwich structure. LDH layer protection and OTEOS coating play crucial roles in the high photostability, good hydrophobicity and satisfactory biocompatibility of pigments. In addition, O/Dye-LDHs exhibit rich color and color adjustability. Impressively, we applied mixture composite pigments with different O/SX-LDH-to-O/AG-LDH ratios to formulate an eye shadow cream, which present a series of popular and natural colours with water resistance to enhance one's attractiveness and appearance. This work provides a promising strategy for the design of safe and efficient composite pigments, demonstrating their potential application in the field of makeup. [ABSTRACT FROM AUTHOR]

Background: The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and its subsequent Omicron variant has raised concerns for chronic obstructive pulmonary disease (COPD) patients due to the potential risk of disruptions to healthcare services and unknown comorbidities between COPD and Omicron. Method: In this study, we conducted a follow‐up investigation of 315 COPD patients during the Omicron outbreak at Shanxi Bethune Hospital to understand the impact of the pandemic on this vulnerable population. Among all patients, 228 were infected with Omicron, of which 82 needed hospitalizations. Result: We found that COPD patients with high blood eosinophil (EOS) counts exhibited lower susceptibility to Omicron infection and were more likely to have milder symptoms that did not require hospitalization. Conversely, patients with low EOS counts showed higher rates of infection and hospitalization. Moreover, EOS count was positively correlated with T lymphocyte counts in hospitalized patients after Omicron infection, suggesting potential associations between EOS and specific immune responses in COPD patients during viral infections. Correlation analysis revealed a positive correlation between EOS count and lymphocyte and T‐cells, and a negative correlation between EOS count and age, neutrophil, and C‐reactive protein. Conclusion: Overall, our study contributes to the knowledge of COPD management during the COVID‐19 Omicron outbreak and emphasizes the importance of considering individual immune profiles to improve care for COPD patients in the face of the ongoing global health crisis. [ABSTRACT FROM AUTHOR]

We aimed to identify the key potential insulin resistance (IR)-related genes and investigate their correlation with immune cell infiltration in type 2 diabetes (T2D). The GSE78721 dataset (68 diabetic patients and 62 controls) was downloaded from the Gene Expression Omnibus database and utilized for single-sample gene set enrichment analysis. IR-related genes were obtained from the Comparative Toxicology Genetics Database, and the final IR-differentially expressed genes (DEGs) were screened by intersecting with the DEGs obtained from the GSE78721 datasets. Functional enrichment analysis was performed, and the networks of the target gene with microRNA, transcription factor, and drug were constructed. Hub genes were identified based on a protein–protein interaction network. Least absolute shrinkage and selection operator regression and Random Forest and Boruta analysis were combined to screen diagnostic biomarkers in T2D, which were validated using the GSE76894 (19 diabetic patients and 84 controls) and GSE9006 (12 diabetic patients and 24 controls) datasets. Quantitative real-time polymerase chain reaction was performed to validate the biomarker expression in IR mice and control mice. In addition, infiltration of immune cells in T2D and their correlation with the identified markers were computed using CIBERSORT. We identified differential immune gene set regulatory T-cells in the GSE78721 dataset, and T2D samples were assigned into three clusters based on immune infiltration. A total of 2094 IR-DEGs were primarily enriched in response to endoplasmic reticulum stress. Importantly, HDAC9 and ARRDC4 were identified as markers of T2D and associated with different levels of immune cell infiltration. HDAC9 mRNA level were higher in the IR mice than in control mice, while ARRDC4 showed the opposite trend. In summary, we discovered potential vital biomarkers that contribute to immune cell infiltration associated with IR, which offers a new sight of immunotherapy for T2D. [ABSTRACT FROM AUTHOR]

Efficient and inexpensive electrocatalysts play an important role in the hydrogen evolution reaction (HER) of electrolytic water splitting. Herein, Ni2P-MoC/coal-based carbon fiber (Ni2P-MoC/C-CF) self-supporting catalysts were obtained by low-temperature phosphorization and high-temperature carbonization. The Mo source and oxidized coal were uniformly dispersed in the carbon support by electrospinning technology. A precursor of Ni was introduced by the impregnation method. The synergistic effect of MoC and Ni2P may reduce the strong hydrogen adsorption capacity of pure MoC and provide a fast hydrogen release process. In addition, the C-CFs prepared by electrospinning can not only prevent the agglomeration of MoC and Ni2P particles at a high temperature but also provide a self-supporting support for the catalyst. As a result, the catalytic performance of the HER was improved greatly, and a low overpotential of 112 mV at 10 mA cm−2 was exhibited stably by the Ni2P-MoC/C-CFs. This work not only converts coal into coal-based carbon materials but also provides a feasible pathway for the rational design of large-scale molded hydrogen electrocatalysts. [ABSTRACT FROM AUTHOR]

Background: Patients with non-alcoholic fatty liver disease (NAFLD) often exhibit hepatic steatosis and dyslipidemia. Studies have shown that intestinal microorganisms are closely related to the occurrence of NAFLD and atherosclerosis. Our previous study has underscored the protective role of microRNA-30a-5p (miR-30a-5p) against atherosclerosis., Methods and Results: In the present study, we aimed to elucidate the effect and underlying mechanism of the intestinal microorganisms of miR-30a-5p knockout (KO) mice on NAFLD. Our findings demonstrated that KO exacerbated high-fat diet (HFD)-induced hepatic steatosis and disrupted liver function, as evidenced by elevated levels of total cholesterol, low-density lipoprotein, alanine aminotransferase, aspartate transaminase, and total bile acids in serum. Fecal microbiota from HFD-fed KO mice induced hepatic steatosis, dyslipidemia, and higher levels of enzymes indicative of liver damage in wild-type mice. Remarkably, KO mice significantly intensified the above effects. 16s rDNA sequencing and metabolomics of the intestinal microbiota in the HFD-treated KO and WT mice showed that the loss of miR-30a-5p resulted in intestinal microbiota imbalance and was highly related to the arachidonic acid metabolic pathway. Targeted metabolomic in the liver tissues unveiled upregulation of COX-related (PGF2a, 8-iso-PGF2a and PGF2) and LOX-related (LTB4, LTD4, 12S-HETE and 15S-HETE) factors in HFD-treated KO mice. Immunohistochemistry and transcriptional analyses showed that miR-30a-5p affected arachidonic acid metabolism through the LOX/COX pathways. Besides, COX/LOX pathways and hepatic steatosis were reversed after reintroducing miR-30a-5p in HFD-treated KO mice., Conclusions: This study reveals the pivotal mechanism by which miR-30a-5p and intestinal microbes regulate hepatic steatosis and abnormal lipid metabolism, offering promising avenues for NAFLD and atherosclerosis therapeutics., Highlights: MiR-30a-5p deletion aggravated hepatic steatosis and lipid disorder induced by an HFD in mice. Gut microbiota participated in the regulation of hepatic steatosis in the context of miR-30a-5p. Gut microbiota metabolism-related arachidonic acid metabolic pathway contributed to miR-30a-5p-regulated hepatic steatosis and lipid disorder. Reintroducing miR-30a-5p reversed hepatic steatosis and arachidonic acid metabolism disorder caused by HFD and miR-30a-5p deletion., (© 2024 The Author(s). Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

To find highly effective and low-toxicity antitumor drugs to overcome the challenge of cancer, we designed and synthesized a series of novel 4-oxobutanamide derivatives using the principle of molecular hybridization and tested the antiproliferative ability of the title compounds against human cervical carcinoma cells (HeLa), human breast carcinoma cells (MDA-MB-231) and human kidney carcinoma cells (A498). Among them, N 1 -(4-methoxybenzyl)-N 4 -(4-methoxyphenyl)-N 1 -(3,4,5-trimethoxyphenyl) succinimide DN4 (IC 50  = 1.94 µM) showed the best proliferation activity on A498, superior to the positive control paclitaxel (IC 50  = 8.81 µM) and colchicine (IC 50  = 7.17 µM). Compound DN4 not only inhibited the proliferation, adhesion and invasion of A498, but also inhibited angiogenesis and tumor growth in a dose-dependent manner in the xenograft model of A498 cells. In addition, we also predicted the physicochemical properties and toxicity (ADMET) of these derivatives, and the results suggested that these derivatives may have the absorption, distribution, metabolism, excretion, and toxicity properties of drug candidates. Thus, compound DN4 may be a promising drug candidate for the treatment of cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The integration of biochar (BC) production from organic waste with ampicillin (AMP), an emerging pollutant, adsorption is a novel and promising treatment approach. In this study, peanut shells, coffee grounds, digestates, and oyster shells were used for BC production. Among these, the use of anaerobic digestate from food waste fermentation to produce extracts for antibiotic adsorption is relatively unexplored. The pyrolysis temperature was determined using thermogravimetric analysis (TGA) and the materials were characterized with BET, SEM, FTIR, and XRD. The TGA results indicate that PSB, CRB, and DSB underwent pyrolysis involving cellulose, hemicellulose, and lignin, whereas OSB underwent crystal formation. Characterization revealed that DSB has more functional groups, a superior mesoporous structure, appropriate O/C ratio, and trace amounts of calcite crystals, which are favorable for AMP adsorption. Adsorption experiments demonstrate that all four materials adhere to the Freundlich and Langmuir isotherm and Elovich kinetic models, indicating predominant physical adsorption, with some chemical adsorption also present. Thermodynamic studies demonstrate that BC is spontaneous during adsorption and is a heat-absorbing reaction. DSB exhibits the strongest AMP adsorption. A 53.81 mg g -1 adsorbance was obtained at a dosage of 150 mg, pH = 2, and 60 °C. This study introduces innovative approaches for managing waste types and provides data to support the selection of suitable solid wastes for the preparation of BC with excellent adsorption properties. Furthermore, it lays the groundwork for future studies aimed at enhancing the AMP treatment efficacy., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

The choline-glycine betaine pathway plays an important role in bacterial survival in hyperosmotic environments. Osmotic activation of the choline transporter BetT promotes the uptake of external choline for synthesizing the osmoprotective glycine betaine. Here, we report the cryo-electron microscopy structures of Pseudomonas syringae BetT in the apo and choline-bound states. Our structure shows that BetT forms a domain-swapped trimer with the C-terminal domain (CTD) of one protomer interacting with the transmembrane domain (TMD) of a neighboring protomer. The substrate choline is bound within a tryptophan prism at the central part of TMD. Together with functional characterization, our results suggest that in Pseudomonas species, including the plant pathogen P. syringae and the human pathogen Pseudomonas aeruginosa , BetT is locked at a low-activity state through CTD-mediated autoinhibition in the absence of osmotic stress, and its hyperosmotic activation involves the release of this autoinhibition.

The global burden of infections due to the pathogenic fungus Cryptococcus is substantial in persons with low CD4 + T-cell counts. Previously, we deleted three chitin deacetylase genes from Cryptococcus neoformans to create a chitosan-deficient, avirulent strain, designated as cda1∆2∆3∆ , which, when used as a vaccine, protected mice from challenge with virulent C. neoformans strain KN99. Here, we explored the immunological basis for protection. Vaccine-mediated protection was maintained in mice lacking B cells or CD8 + T cells. In contrast, protection was lost in mice lacking α/β T cells or CD4 + T cells. Moreover, CD4 + T cells from vaccinated mice conferred protection upon adoptive transfer to naive mice. Importantly, while monoclonal antibody-mediated depletion of CD4 + T cells just prior to vaccination resulted in complete loss of protection, significant protection was retained in mice depleted of CD4 + T cells after vaccination but prior to challenge. Vaccine-mediated protection was lost in mice genetically deficient in interferon-γ (IFNγ), tumor necrosis factor alpha (TNFα), or interleukin (IL)-23p19. A robust influx of leukocytes and IFNγ- and TNFα-expressing CD4 + T cells was seen in the lungs of vaccinated and challenged mice. Finally, a higher level of IFNγ production by lung cells stimulated ex vivo correlated with lower fungal burden in the lungs. Thus, while B cells and CD8 + T cells are dispensable, IFNγ and CD4 + T cells have overlapping roles in generating protective immunity prior to cda1∆2∆3∆ vaccination. However, once vaccinated, protection becomes less dependent on CD4 + T cells, suggesting a strategy for vaccinating HIV + persons prior to loss of CD4 + T cells., Importance: The fungus Cryptococcus neoformans is responsible for >100,000 deaths annually, mostly in persons with impaired CD4 + T-cell function such as AIDS. There are no approved human vaccines. We previously created a genetically engineered avirulent strain of C. neoformans , designated as cda1∆2∆3∆ . When used as a vaccine, cda1∆2∆3∆ protects mice against a subsequent challenge with a virulent C. neoformans strain. Here, we defined components of the immune system responsible for vaccine-mediated protection. We found that while B cells and CD8 + T cells were dispensible, protection was lost in mice genetically deficient in CD4 + T cells and the cytokines IFNγ, TNFα, or IL-23. A robust influx of cytokine-producing CD4 + T cells was seen in the lungs of vaccinated mice following infection. Importantly, protection was retained in mice depleted of CD4 + T cells following vaccination, suggesting a strategy to protect persons who are at risk of future CD4 + T-cell dysfunction., Competing Interests: The authors declare no conflict of interest.

In spite of the increasing popularity of project-based collaborative learning (PBCL) as a pedagogy, real successful collaboration cannot always be achieved due to the cognitive, motivational and social emotional challenges students encounter during collaboration. Recognizing the challenges and developing regulation strategies to cope with the challenges at both individual and group level is essential for successful collaboration. In the last decades, a growing interest has been developed around socially shared regulation of emotions and how it is interwoven with self-regulation and co-regulation. However, capturing the process of students' emotional challenges and regulations in a long and dynamic project proves difficult and there remains a paucity of evidence on how co-regulation and socially-shared regulation co-occur with learners' cognitive and emotional progress in project-based collaborative learning. The purpose of the present study is to investigate and identify what kind of social emotional challenges students encountered during PBCL and how they regulate themselves and the groups in order to finish the projects. A quasi-experimental research design was adopted in an academic English classroom, with thirty-eight students self-reporting their challenges and regulations three times after finishing each of the projects. The results of qualitative analysis plus a case study of two groups indicate that students encounter a variety of social emotional challenges and employed different levels of co-regulation and socially shared regulation in addition to self-regulation, leading to varying collaboration results and experiences. The findings of the study offer insights into the emotional regulation in PBCL and shed light for future design of pedagogical interventions aiming at supporting socially shared regulation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Huang, Wang and Han.)

Streptococcus agalactiae ( S.agalactiae ), also known as group B Streptococcus (GBS), is a highly infectious pathogen. Prolonged antibiotic usage leads to significant issues of antibiotic residue and resistance. Chelerythrine (CHE) is a naturally occurring benzophenidine alkaloid and chelerythrine chloride (CHEC) is its hydrochloride form with diverse biological and pharmacological activities. However, the antibacterial mechanism of CHEC against GBS remains unclear. Thus, this study aims to investigate the in vitro antibacterial activity of CHEC on GBS and elucidate its underlying mechanism. The antibacterial effect of CHEC on GBS was assessed using inhibitory zone, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) assays, as well as by constructing a time-kill curve. The antibacterial mechanism of CHEC was investigated through techniques such as scanning electron microscopy (SEM) and transmission electron microscopy (TEM), measurement of alkaline phosphatase (AKP) activity, determination of Na + K + , Ca 2+ Mg 2+ -adenosine triphosphate (ATP) activity, observation of membrane permeability, and analysis of intracellular reactive oxygen species (ROS) and mRNA expression levels of key virulence genes. The results demonstrated that the inhibition zone diameters of CHEC against GBS were 14.32 mm, 12.67 mm, and 10.76 mm at concentrations of 2 mg/mL, 1 mg/mL, and 0.5 mg/mL, respectively. The MIC and MBC values were determined as 256 μg/mL and 512 μg/mL correspondingly. In the time-kill curve, 8 × MIC, 4 × MIC and 2 × MIC CHEC could completely kill GBS within 24 h. SEM and TEM analyses revealed significant morphological alterations in GBS cells treated with CHEC including shrinkage, collapse, and leakage of cellular fluids. Furthermore, the antibacterial mechanism underlying CHEC's efficacy against GBS was attributed to its disruption of cell wall integrity as well as membrane permeability resulting in extracellular release of intracellular ATP, AKP, Na + K + , Ca 2+ Mg 2+ . Additionally CHEC could increase the ROS production leading to oxidative damage and downregulating mRNA expression levels of key virulence genes in GBS cells. In conclusion, CHEC holds potential as an antimicrobial agent against GBS and further investigations are necessary to elucidate additional molecular mechanisms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Xin, Pu, Wang, Gu, He, Du, Tang and Han.)

Background: Maternal smoking during pregnancy (MSDP) is a known risk factor for offspring developing chronic obstructive pulmonary disease (COPD), but the underlying mechanism remains unclear., Objective: This study aimed to explore whether the increased COPD risk associated with MSDP could be attributed to tobacco dependence (TD)., Methods: This case-control study used data from the nationwide cross-sectional China Pulmonary Health study, with controls matched for age, sex, and smoking status. TD was defined as smoking within 30 minutes of waking, and the severity of TD was assessed using the Fagerstrom Test for Nicotine Dependence. COPD was diagnosed when the ratio of forced expiratory volume in 1 second to forced vital capacity was <0.7 in a postbronchodilator pulmonary function test according to the 2017 Global Initiative for Chronic Obstructive Lung Disease criteria. Logistic regression was used to examine the correlation between MSDP and COPD, adjusting for age, sex, BMI, educational attainment, place of residence, ethnic background, occupation, childhood passive smoking, residential fine particulate matter, history of childhood pneumonia or bronchitis, average annual household income, and medical history (coronary heart disease, hypertension, and diabetes). Mediation analysis examined TD as a potential mediator in the link between MSDP and COPD risk. The significance of the indirect effect was assessed through 1000 iterations of the "bootstrap" method., Results: The study included 5943 participants (2991 with COPD and 2952 controls). Mothers of the COPD group had higher pregnancy smoking rates (COPD: n=305, 10.20%; controls: n=211, 7.10%; P<.001). TD was more prevalent in the COPD group (COPD: n=582, 40.40%; controls: n=478, 33.90%; P<.001). After adjusting for covariates, MSDP had a significant effect on COPD (β=.097; P<.001). There was an association between MSDP and TD (β=.074; P<.001) as well as between TD and COPD (β=.048; P=.007). Mediation analysis of TD in the MSDP-COPD association showed significant direct and indirect effects (direct: β=.094; P<.001 and indirect: β=.004; P=.03). The indirect effect remains present in the smoking population (direct: β=.120; P<.001 and indirect: β=.002; P=.03)., Conclusions: This study highlighted the potential association between MSDP and the risk of COPD in offspring, revealing the mediating role of TD in this association. These findings contribute to a deeper understanding of the impact of prenatal tobacco exposure on lung health, laying the groundwork for the development of relevant prevention and treatment strategies., (©Jinxuan Li, Jianying Xu, Lan Yang, Yongjian Xu, Xiangyan Zhang, Chunxue Bai, Jian Kang, Pixin Ran, Huahao Shen, Fuqiang Wen, Kewu Huang, Wanzhen Yao, Tieying Sun, Guangliang Shan, Ting Yang, Yingxiang Lin, Jianguo Zhu, Ruiying Wang, Zhihong Shi, Jianping Zhao, Xianwei Ye, Yuanlin Song, Qiuyue Wang, Gang Hou, Yumin Zhou, Wen Li, Liren Ding, Hao Wang, Yahong Chen, Yanfei Guo, Fei Xiao, Yong Lu, Xiaoxia Peng, Biao Zhang, Zuomin Wang, Hong Zhang, Xiaoning Bu, Xiaolei Zhang, Li An, Shu Zhang, Zhixin Cao, Qingyuan Zhan, Yuanhua Yang, Lirong Liang, Bin Cao, Huaping Dai, Kian Fan Chung, Zhengming Chen, Jiang He, Sinan Wu, Dan Xiao, Chen Wang, China Pulmonary Health Study Group. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 22.02.2024.)