Biointerfacial supramolecular self-assembly of whey protein isolate nanofibrils on probiotic surface to enhance survival and application to 3D printing dysphagia foods.

Personalized three-dimensional (3D) printed foods rich in probiotics were investigated. Lactiplantibacillus plantarum (Lp), as a representative of probiotics, was used to investigate the 3D printing of probiotic-rich dysphagia foods. Here, whey protein isolate nanofibrils (WPNFs) were coated and anchored on bacterial surfaces via biointerfacial supramolecular self-assembly, providing protection against environmental stress and the 3D printing process. The optimized composite gels consisting of High acyl gellan gum (0.25 g), whey protein isolate (1.25 g), fructooligosaccharides (0.75 g), Lp-WPNFs-Glyceryl tributyrate emulsion (Φ = 40%, 3.75 mL) can realize 3D printing, and exhibit high resolution, and stable shape. The viable cell count is higher than 8.0 log CFU/g. They are particularly suitable for people with dysphagia and are classified as level 5-minced & moist in the international dysphagia diet standardization initiative framework. The results provide new insights into the development of WPNFs-coating on bacterial surfaces to deliver probiotics and 3D printed food rich in probiotics.

Kick Vaping: Feasibility, acceptability, and preliminary impact of a vaping cessation text messaging intervention for Latino young adults.

OBJECTIVE: To assess the feasibility, acceptability, and preliminary impact of Kick Vaping among Latino young adults. METHODS: Forty Latino young adults (ages 18 to 25) who were currently vaping received Kick Vaping, a vaping cessation text messaging intervention available in English and Spanish. Feasibility was measured by the eligibility, enrollment, and follow-up rates. Acceptability was measured by overall satisfaction with the intervention. Preliminary impact was measured by self-reported 7-day point prevalence abstinence and changes in self-efficacy. RESULTS: Two hundred three individuals were identified, 61 were assessed for eligibility, and 55 were eligible. Forty individuals consented to participate and were enrolled in Kick Vaping. At baseline, most participants used disposable devices (70%), vaped daily (97.5%), had low (37.5%) or medium (35.0%) e-cigarette dependence, and had attempted to quit in the past year (72.5%). At Month 3, the follow-up rate was 90% (36/40). Treating those lost to follow-up as participants who continued vaping, 75% (30/40) of participants self-reported 7-day point prevalence abstinence. Self-efficacy mean scores significantly increased from 30.65 (SD 8.07) at baseline to 50.11 (SD 10.57) at follow-up (p < 0.01). Most participants (88.9%, 32/36) reported being satisfied/extremely satisfied with Kick Vaping. CONCLUSION: It is feasible to recruit and retain Latino young adults in a vaping cessation text messaging intervention. Kick Vaping generated high satisfaction among Latino young adults, significantly increased self-efficacy, and resulted in a notable vaping cessation rate at Month 3. Additional testing in a randomized controlled trial is warranted to assess the efficacy of the intervention.

Public perceptions and discussions of synthetic nicotine on Twitter.

Background: As alternative replacement products for tobacco-derived nicotine, synthetic nicotine products have recently emerged and gained increasing popularity. This study analyzes public perception and discussion of synthetic nicotine products on Twitter (now "X"). Methods: Through Twitter streaming API (Application Programming Interface), we have collected 2,764 Twitter posts related to synthetic nicotine from December 12, 2021, to October 17, 2022, using keywords related to synthetic nicotine. By applying an inductive approach, two research assistants manually determined the relevance of tweets to synthetic nicotine products and assessed the attitude of tweets as positive, negative, and neutral of tweets toward synthetic nicotine, and the main topics. Results: Among 1,007 tweets related to synthetic nicotine products, the proportion of negative tweets (383/1007, 38.03%) toward synthetic nicotine products was significantly higher than that of positive tweets (218/1007, 21.65%) with a p-value <0.05. Among negative tweets, major topics include the concern about addiction and health risks of synthetic nicotine products (44.91%) and synthetic nicotine as a policy loophole (31.85%). Among positive tweets, top topics include alternative replacement for nicotine (39.91%) and reduced health risks (31.19%). Conclusion: There are mixed attitudes toward synthetic nicotine products on Twitter, resulting from different perspectives. Future research could incorporate demographic information to understand the attitudes of various population groups.

Murine HSD17ß13 does not control liver steatosis and modestly impacts fibrosis in a sex- and diet-specific manner.

Human genetic studies show that loss of function mutations in 17-Beta hydroxysteroid dehydrogenase (HSD17ß13) are associated with protection from non-alcoholic steatohepatitis (NASH). As a result, therapies which reduce HSD17ß13 are being pursued for the treatment of NASH. However, inconsistent effects on steatosis, inflammation and fibrosis pathogenesis have been reported in murine Hsd17b13 knockdown or knockout models. To clarify whether murine Hsd17b13 loss regulates liver damage and fibrosis, we characterized Hsd17b13 knockout mice subjected to pro-NASH diets or pro-inflammatory chemical-induced liver injury. There were no effects of Hsd17b13 loss on liver injury, inflammation, fibrosis or lipids after 28 weeks on the Gubra-Amylin NASH (GAN) diet or 12 weeks on a 45% choline deficient high fat diet (CDAHFD). However, AAV-mediated re-expression of murine Hsd17b13 in KO mice increased liver macrophage abundance in both sexes fed the 45% CDAHFD. In contrast, there was a modest reduction in liver fibrosis, but not lipids or inflammation within Hsd17b13 null female, but not male, mice after 12 weeks of a 60% CDAHFD compared to WT littermates. Fibrosis and the abundance of liver macrophages were increased in Hsd17b13 KO females upon adenoviral re-expression of mouse HSD17ß13, but this was not reflected in inflammatory markers. Additionally, we found minimal differences in liver injury, lipids, or inflammatory and fibrotic markers 48 hours after acute CCl4 exposure. In summary, murine Hsd17b13 loss has modest diet- and sex-specific effects on liver fibrosis which contrasts with human genetic studies. This suggests a disconnect between the biological function of HSD17ß13 in mice and humans.

Exploring the molecular landscape of osteosarcoma through PTTG family genes using a detailed multi-level methodology.

Background: Osteosarcoma (OS) poses a significant clinical challenge, necessitating a comprehensive exploration of its molecular underpinnings. Methods: This study explored the roles of PTTG family genes (PTTG1, PTTG2, and PTTG3P) in OS, employing a multifaceted approach encompassing molecular experiments, including OS cell lines culturing, RT-qPCR, bisulfite and Whole Exome Sequencing (WES) and in silico experiments, including The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets-based validation, overall survival, gene enrichment, functional assays, and molecular docking analyses. Results: Our findings reveal a consistent up-regulation of PTTG genes in OS cell lines, supported by RT-qPCR experiments and corroborated across various publically available expression datasets databases. Importantly, ROC curve analyses highlight their potential as diagnostic markers. Moving beyond expression profiles, we unveil the epigenetic landscape by demonstrating significant hypomethylation of CpG islands associated with PTTG genes in OS. The negative correlation between methylation status and mRNA expression emphasizes the regulatory role of promoter methylation in PTTG gene expression. Contrary to expectations, genetic mutations in PTTG genes are rare in OS, with only benign mutations observed. Moreover, functional assays also confirmed the oncogenic roles of the PTTG gene in the development of OS. Lastly, we also revealed that Calcitriol is the most appropriate drug that can be utilized to treat OS in the context of PTTG genes. Conclusion: The identification of PTTG genes as potential diagnostic markers and their association with epigenetic alterations opens new avenues for understanding OS pathogenesis and developing targeted therapies. As we navigate the complex landscape of OS, this study contributes essential insights that may pave the way for improved diagnostic and therapeutic strategies in its management.

Joint extraction of Chinese medical entities and relations based on RoBERTa and single-module global pointer.

BACKGROUND: Most Chinese joint entity and relation extraction tasks in medicine involve numerous nested entities, overlapping relations, and other challenging extraction issues. In response to these problems, some traditional methods decompose the joint extraction task into multiple steps or multiple modules, resulting in local dependency in the meantime. METHODS: To alleviate this issue, we propose a joint extraction model of Chinese medical entities and relations based on RoBERTa and single-module global pointer, namely RSGP, which formulates joint extraction as a global pointer linking problem. Considering the uniqueness of Chinese language structure, we introduce the RoBERTa-wwm pre-trained language model at the encoding layer to obtain a better embedding representation. Then, we represent the input sentence as a third-order tensor and score each position in the tensor to prepare for the subsequent process of decoding the triples. In the end, we design a novel single-module global pointer decoding approach to alleviate the generation of redundant information. Specifically, we analyze the decoding process of single character entities individually, improving the time and space performance of RSGP to some extent. RESULTS: In order to verify the effectiveness of our model in extracting Chinese medical entities and relations, we carry out the experiments on the public dataset, CMeIE. Experimental results show that RSGP performs significantly better on the joint extraction of Chinese medical entities and relations, and achieves state-of-the-art results compared with baseline models. CONCLUSION: The proposed RSGP can effectively extract entities and relations from Chinese medical texts and help to realize the structure of Chinese medical texts, so as to provide high-quality data support for the construction of Chinese medical knowledge graphs.

ESL attenuates BLM-induced IPF in mice: Dual mediation of the TLR4/NF-κB and TGF-ß1/PI3K/Akt/FOXO3a pathways.

BACKGROUNDS: Idiopathic pulmonary fibrosis (IPF) is a persistent and advanced pulmonary ailment. The roles of innate immunity and adaptive immunity are pivotal in the evolution of IPF. An ill-adjusted interaction between epithelial cells and immune cells is responsible for initiating the epithelial-mesenchymal transition (EMT) process and sustaining chronic inflammation, thereby fostering fibrosis progression. The intricacy of IPF pathogenesis has hindered the availability of efficacious agents. Elephantopus scaber Linn. (ESL) is a canonical Chinese medicine with significant immunoregulatory effects, and its aqueous extract has been proven to attenuate IPF symptoms in bleomycin (BLM)-induced mice. However, the underlying mechanism through which ESL relieves IPF remains unclear. AIM: To validate whether ESL reverses IPF by mediating the immune response and EMT. METHODS: Ultra-performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS) and UPLC were used to identify the components and determine the concentrations of the specific compounds in the ESL. Network pharmacology and molecular docking were applied to predict the potential mechanism underlying the anti-IPF effect of ESL. BLM-induced IPF mice were used to validate the anti-IPF effect of ESL, and lung tissue was collected to test putative pathways involved in inflammation and EMT via immunohistochemistry (ICH), real-time quantitative polymerase chain reaction (RT-qPCR) and Western blotting. RESULTS: Sixty-one compounds were identified, and thirteen main ingredients were quantified in the ESL. In silico experiments predicted that the IPF-mediated reversal of adverse effects by ESL would be related to interruption of the Toll-like receptor 4 (TLR4)/nuclear factor-k-gene binding (NF-ĸB) inflammatory pathway and the transforming growth factor-beta l (TGF-ß1)/phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/forkhead box O3 (FOXO3a) fibrosis pathway. In vivo experiments showed that ESL alleviates BLM-induced lung inflammation and fibrosis by reducing neutrophil aggregation and fibroblast foci, similar to the effects of the positive control drug pirfenidone (PFD). ESL markedly inhibited the transcription of TNF-α, IL-1ß, and IL-6, which are downstream genes of the NF-κB signaling pathway. Furthermore, the protein levels of TLR4 and p-NF-κB were correspondingly inhibited in response to ESL treatment. Additionally, ESL reverses BLM-induced changes in the expression of EMT-related biological characteristic indicators (collagen I [COLIA1], E-cadherin, and alpha smooth muscle actin [α-SMA]) at the messenger ribonucleic acid (mRNA) level and markedly inhibits the expression of EMT-related upstream proteins (TGF-ß1, p-PI3K, p-Akt, and p-FOXO3a). CONCLUSION: Our research suggested that ESL attenuates BLM-induced IPF through mediating the EMT process via the TGF-ß1/PI3K/Akt/FOXO3a signaling pathway and inhibiting inflammation through the TLR4/NF-κB signaling pathway, highlighting that ESL can serve as an immunoregulator for relieving the abnormal immune response and reversing the EMT in IPF.

Different stages of flavor variations among canned Antarctic krill (Euphausia superba): Based on GC-IMS and PLS-DA.

The aim of the present study was to explore changes in the profile of volatile compounds (VCs) in canned Antarctic krill (Euphausia superba) at different processing stages using partial least squares discriminant analysis (PLS-DA) and gas chromatography-mass spectrometry (GC-IMS). A total of 43 VCs were detected using GC-IMS in all krill meat samples, which included mainly alcohols, aldehydes, ketones, esters, and furans. Considering the different processing stages, the highest variation in VCs and the highest VC content were observed in krill meat which underwent both blanching and salt addition. PLS-DA further revealed flavor differences in canned Antarctic krill meat at different processing stages, with octanal, 2-hexanol, 2-octane, 2,3,5-trimethyl pyrazine, and cis-3-hexanol as the main contributors to observed differences in VC profiles. These findings contribute to the production of high-quality canned krill meat, enhancing its flavor quality and providing a feasible theoretical basis for future krill meat pretreatment and industry development.

Microcystin-LR prenatal exposure induces coronary heart disease through macrophage polarization imbalance mediated by trophoblast-derived extracellular vesicles.

Microcystin-leucine arginine (MC-LR) has been reported to exhibit placental toxicity, leading to potential adverse pregnancy outcomes. Placental abnormalities often coincide with congenital heart defects (CHD). However, the extent to which MC-LR-induced placental abnormalities contribute to CHD and the cellular mechanisms underlying this association remain unknown. In this study, we observed abnormal polarization of placental macrophages in pregnant mice exposed to MC-LR during pregnancy, and the embryos developed cardiac developmental defects that persisted into adulthood. Trophoblast-derived extracellular vesicles (T-EVs) increase in number during pregnancy and act as a critical signal in macrophage polarization. However, MC-LR significantly affected the miRNA expression profile of T-EVs. Upon internalization into macrophages, T-EV-derived miR-377-3p specifically targets the 3'UTR region of NR6A1 to inhibit gene expression. Silencing of transcription suppressor NR6A1 leads to abnormal activation of the downstream mTOR/S6K1/SREBP pathway, inducing metabolic reprogramming and ultimately leading to M1 polarization of macrophages. This study elucidated the placental mechanism underlying MC-LR-induced CHD for the first time, providing insights into the environmental risks associated with CHD.

Chronic exposure to polystyrene microplastics induced LHR reduction and decreased testosterone levels through NF-κB pathway.

The extensive utilization of plastic products in recent years has resulted in a significant contamination of microplastics (MPs). The ingestion of MPs by aquatic and terrestrial organisms facilitates their transmission to mammals through the food chain. Therefore, the toxicity of MPs has attracted widespread attention from researchers. Previous studies have shown a connection between being exposed to polystyrene MPs (PS-MPs) and issues with male reproductive function. Testosterone, a hormone essential for male reproductive function, is produced and secreted by specialized cells known as Leydig cells, which found in the testicular interstitium. In our prior research, we confirmed that exposure to PS-MPs caused a reduction in testosterone levels by interfering with the LH-mediated LHR/cAMP/PKA/StAR pathway, with LHR being pivotal in this mechanism. However, the molecular mechanism underlying PS-MPs-induced reduction of LHR remains unclear. In this study, mice were respectively given drinking water containing 1000 µg/L PS-MPs characterized by diameters of 0.5 µm, 4 µm, and 10 µm for a period of 180 days. Our findings indicated that exposure to PS-MPs resulted in the proliferation of macrophages as well as their polarization towards the M1 phenotype. Additionally, the presence of PS-MPs triggered the release of tumor necrosis factor alpha (TNF-α) from macrophages, thereby activating nuclear factor-κB (NF-κB) signaling pathway within Leydig cells. The translocation of NF-κB into nucleus facilitated its binding to the promoter region of LHR, which consequently led to the repression of LHR transcription. This transcriptional inhibition resulted in a subsequent suppression of testosterone synthesis and secretion. Overall, this study elucidates a theoretical basis for explaining the interference of PS-MPs on the testosterone synthesis and secretion in Leydig cells from the perspective of the interaction between cells in the testicular interstitium.

Toxicity of Waterpipe Tobacco Smoking: The Role of Flavors, Sweeteners, Humectants, and Charcoal.

Waterpipe tobacco (WPT) smoking is a public health concern, particularly among youth and young adults. The global spread of WPT use has surged since the introduction of pre-packaged flavored and sweetened WPT, which is widely marketed as a safer tobacco alternative. Besides flavorants and sugars, WPT additives include humectants, which enhance the moisture and sweetness of WPT, act as solvents for flavors, and impart smoothness to the smoke, thus increasing appeal to users. In the United States (U.S.), unlike cigarette tobacco flavoring (with the exception of menthol), there is no FDA product standard or policy in place prohibiting sales of flavored WPT. Research has shown that the numerous fruit, candy, and alcohol flavors added to WPT entice individuals to experience those flavors, putting them at an increased risk of exposure to WPT smoke-related toxicants. Additionally, burning charcoal briquettes-used as a heating source for WPT-contributes to the harmful health effects of WPT smoking. This review presents existing evidence on the potential toxicity resulting from humectants, sugars, and flavorants in WPT, and from the charcoal used to heat WPT. The review discusses relevant studies of inhalation toxicity in animal models and of biomarkers of exposure in humans. Current evidence suggests that more data are needed on toxicant emissions in WPT smoke to inform effective tobacco regulation to mitigate the adverse impact of WPT use on human health.

MAPK4 facilitates angiogenesis by inhibiting the ERK pathway in non-small cell lung cancer.

Background: Angiogenesis plays an important role in the occurrence and development of non-small cell lung cancer (NSCLC). The atypical mitogen-activated protein kinase 4 (MAPK4) has been shown to be involved in the pathogenesis of various diseases. However, the potential role of MAPK4 in the tumor angiogenesis of NSCLC remains unclear. Methods: Adult male C57BL/6 wild-type mice were randomly divided into the control group and p-siMAPK4 intervention group, respectively. The cell proliferation was analyzed with flow cytometry and immunofluorescence staining. The vascular density in tumor mass was analyzed by immunofluorescence staining. The expressions of MAPK4 and related signaling molecules were detected by western blot analysis and immunofluorescence staining, and so on. Results: We found that the expression of MAPK4, which was dominantly expressed in local endothelial cells (ECs), was correlated with tumor angiogenesis of NSCLC. Furthermore, MAPK4 silencing inhibited the proliferation and migration abilities of human umbilical vein ECs (HUVECs). Global gene analysis showed that MAPK4 silencing altered the expression of multiple genes related to cell cycle and angiogenesis pathways, and that MAPK4 silencing increased transduction of the extracellular regulated protein kinases 1/2 (ERK1/2) pathway but not Akt and c-Jun n-terminal kinase pathways. Further analysis showed that MAPK4 silencing inhibited the proliferation and migration abilities of HUVECs cultured in tumor cell supernatant, which was accompanied with increased transduction of the ERK1/2 pathway. Clinical data analysis suggested that the higher expression of MAPK4 and CD34 were associated with poor prognosis of patients with NSCLC. Targeted silencing of MAPK4 in ECs using small interfering RNA driven by the CD34 promoter effectively inhibited tumor angiogenesis and growth of NSCLC in vivo. Conclusion: Our results reveal that MAPK4 plays an important role in the angiogenesis and development of NSCLC. MAPK4 may thus represent a new target for NSCLC.

Public Perceptions and Discussions of the US Food and Drug Administration's JUUL Ban Policy on Twitter: Observational Study.

BACKGROUND: On June 23, 2022, the US Food and Drug Administration announced a JUUL ban policy, to ban all vaping and electronic cigarette products sold by Juul Labs. OBJECTIVE: This study aims to understand public perceptions and discussions of this policy using Twitter (subsequently rebranded as X) data. METHODS: Using the Twitter streaming application programming interface, 17,007 tweets potentially related to the JUUL ban policy were collected between June 22, 2022, and July 25, 2022. Based on 2600 hand-coded tweets, a deep learning model (RoBERTa) was trained to classify all tweets into propolicy, antipolicy, neutral, and irrelevant categories. A deep learning model (M3 model) was used to estimate basic demographics (such as age and gender) of Twitter users. Furthermore, major topics were identified using latent Dirichlet allocation modeling. A logistic regression model was used to examine the association of different Twitter users with their attitudes toward the policy. RESULTS: Among 10,480 tweets related to the JUUL ban policy, there were similar proportions of propolicy and antipolicy tweets (n=2777, 26.5% vs n=2666, 25.44%). Major propolicy topics included "JUUL causes youth addition," "market surge of JUUL," and "health effects of JUUL." In contrast, major antipolicy topics included "cigarette should be banned instead of JUUL," "against the irrational policy," and "emotional catharsis." Twitter users older than 29 years were more likely to be propolicy (have a positive attitude toward the JUUL ban policy) than those younger than 29 years. CONCLUSIONS: Our study showed that the public showed different responses to the JUUL ban policy, which varies depending on the demographic characteristics of Twitter users. Our findings could provide valuable information to the Food and Drug Administration for future electronic cigarette and other tobacco product regulations.

Analysis of human papillomavirus type 16 E4, E5 and L2 gene variations among women with cervical infection in Xinjiang, China.

BACKGROUND: There is a high incidence of cervical cancer in Xinjiang. Genetic variation in human papillomavirus may increase its ability to invade, spread, and escape host immune response. METHODS: HPV16 genome was sequenced for 90 positive samples of HPV16 infection. Sequences of the E4, E5 and L2 genes were analysed to reveal sequence variation of HPV16 in Xinjiang and the distribution of variation among the positive samples of HPV16 infection. RESULTS: Eighty-one of the 90 samples of HPV16 infection showed variation in HPV16 E4 gene with 18 nucleotide variation sites, of which 8 sites were synonymous variations and 11 missense variations. 90 samples of HPV16 infection showed variation in HPV16 E5 and L2 genes with 16 nucleotide variation sites (6 synonymous, 11 missense variations) in the E5 gene and 100 nucleotide variation sites in L2 gene (37 synonymous, 67 missense variations). The frequency of HPV16 L2 gene missense variations G3377A, G3599A, G3703A, and G3757A was higher in the case groups than in the control groups. CONCLUSIONS: Phylogenetic tree analysis showed that 87 samples were European strains, 3 cases were Asian strains, there were no other variations, and G4181A was related to Asian strains. HPV16 L2 gene missense variations G3377A, G3599A, G3703A, and G3757A were significantly more frequent in the case groups than in the control groups.

A Rapid PCR-Based Diagnostic Method for Skin Infection with Mycobacterium marinum.

Objective: The increasing incidence of chronic skin infections caused by Mycobacterium marinum, coupled with the time-consuming and low detection rates nature of traditional culture and histological-based diagnostic methods, underscores the need for an expedited approach. The study aims to develop a rapid and efficient method for detecting M. marinum with PCR technology. Methods: We designed four pairs of primers based on DNA sequences from GeneBank and prior studies, we utilized both PCR and Real-time PCR to identify M. marinum. Specificity and sensitivity assessments were conducted in vitro by DNAs extracted from M. marinum and other bacterial or fungal cultures. Further validation was performed through the implementation of a mouse skin infection model to optimize and confirm the efficacy of the detection method in both fresh and paraffin-embedded skin tissues. The same PCR testing system was further confirmed with paraffin-embedded skin tissues samples from patients as well. Results: The results of the study indicate promising outcomes for the four-pair primers system. It demonstrated 100% sensitivity in detecting M. marinum from purified cultures, including typical strains and nine clinical isolates, while achieving a specificity of 100%. This specificity was evidenced by the absence of PCR products from 12 bacterial species, 12 fungi species, and six other non-tuberculous mycobacterium (NTM) species. In the animal model, the PCR assay exhibited high detection efficacy for both infected fresh tissues and paraffin-embedded tissues, with a slight superiority observed in fresh tissues. However, the PCR assay exhibited high detection efficacy for clinical paraffin-embedded tissues. These findings collectively underscore the robust detection capabilities of our four-pair primers in both in vitro and in vivo settings. Conclusion: A sensitive and highly specific rapid detection system has been successfully developed that can be used to detect M. marinum in both infected fresh tissues and paraffin-embedded tissues.

Potassium iodide enhances the killing effect of methylene blue mediated photodynamic therapy against F. monophora.

BACKGROUND: Chromoblastomycosis (CMB) is a chronic granulomatous fungal infection that affect the skin and subcutaneous tissues. It is clinically problematic due to limited treatment options, low cure rates, and high rates of relapse. This underscores the necessity for innovative treatment approaches. In this study, potassium iodide (KI) combined with Methylene Blue (MB) mediated antimicrobial photodynamic therapy (PDT) were assessed in the treatment of Fonsecaea monophora (F. monophora) both in vitro and in vivo. And the underlying mechanism that contributes to the efficacy of this treatment approach was investigated. METHODS: In vitro experiments were conducted using different combinations and concentrations of MB, KI, and 660 nm light (60 mW/cm2) to inhibit F. monophora. The study was carried out using colony-forming unit (CFU) counts and scanning electron microscopy (SEM). The production of singlet oxygen (1O2), free iodine (I2), hydrogen peroxide (H2O2), and superoxide anion during the KI combined MB-mediated antimicrobial PDT process was also detected. In vivo experiments were developed using a Balb/c mouse paw infection model with F. monophora and treated with PBS, 10 mM KI, 2 mM MB +100 J/cm² and 10 mM KI+2 mM MB +100 J/cm² respectively. Inflammatory swelling, fungal load and histopathological analyses of the mouse footpads were assessed. RESULTS: KI enhanced the killing effect of MB-mediated antimicrobial PDT on the conidial spores of F. monophora at the cell and infected animal model level. During the process, the main antimicrobial agents in KI combined with MB- mediated antimicrobial PDT could produce stronger toxic active species including free I2 and H2O2. CONCLUSION: KI combined with MB-mediated antimicrobial PDT could be an effective adjunct therapy for treating CBM.

Aggregation-Induced Emission Photosensitizer with Ag(I)-π Interaction-Enhanced Reactive Oxygen Species for Eliminating Multidrug Resistant Bacteria.

Multidrug-resistant (MDR) bacteria pose serious threats to public health due to the lack of effective and biocompatible drugs to kill MDR bacteria. Photodynamic antibacterial therapy has been widely studied due to its low induction of resistance. However, photosensitizers that can efficiently generate reactive oxygen species (ROS) through both type I and type II mechanisms and that have the capability of multiple modes of action are rarely reported. Addressing this issue, we developed a near-infrared-emitting triphenylamine indole iodoethane (TTII) and its silver(I) self-assembled (TTIIS) aggregation-induced emission (AIE) photosensitizer for multimode bacterial infection therapy. TTII can efficiently produce both Type I ROS •OH and Type II ROS 1O2. Interestingly, the Ag(I)-π interaction contributed in TTIIS efficiency promotion of the generation of 1O2. Moreover, by releasing Ag+, TTIIS enabled photodynamic-Ag(I) dual-mode sterilization. As a result, TTIIS achieved an effective enhancement of antibacterial activity, with a 1-2-fold boost against multidrug-resistant Escherichia coli (MDR E. coli). Both TTII and TTIIS at a concentration as low as 0.55 µg mL-1 can kill more than 98% of methicillin resistant Staphylococcus aureus (MRSA) on MRSA-infected full-thickness defect wounds of a mouse, and both TTII and TTIIS were effective in eliminating the bacteria and promoting wound healing.

Fruit flavors in electronic cigarettes (ECIGs) are associated with nocturnal dry cough: A population longitudinal analysis.

Evidence from in vitro and animal models has identified the pulmonary toxicity of flavors in electronic cigarettes (ECIGs); however, less is known from epidemiological studies about the effects of flavors in the respiratory health. This study examined the longitudinal association between exposure to ECIGs flavors and nocturnal dry cough among ECIGs users. A secondary analysis of data from the Population Assessment of Tobacco and Health Study (2014-2019) was conducted. The study population included adults who provided information (n = 18,925) for a total of 38,638 observations. Weighted-incidence estimates and weighted- generalized estimating equation models were performed to assess unadjusted and adjusted associations. The weighted incidence proportion (WIP) of nocturnal dry cough was significantly higher among current (WIP:16.6%; 95%CI 10.5, 21.2) and former fruit flavored ECIGs users (WIP:16.6%; 95%CI 11.3, 21.9) as compared to non-ECIGs users (WIP:11.1%; 95%CI 10.6, 11.6). Current ECIGs users of fruit flavors showed 40% higher risk of reporting cough than non-ECIGs users (aRR:1.40, 95%CI 1.01, 1.94). Former ECIGs users of multiple flavors and other flavors had 300% and 66% higher risk to develop cough, respectively (aRR:3.33, 95%CI 1.51, 7.34 and aRR:1.66, 95%CI 1.0.9, 2.51), relative to non-ECIGs users. We observed a significantly higher risk of developing nocturnal dry cough in the past 12 months in current and former ECIGs users of fruit flavors and in former ECIGs users of multiple flavors. To the extent that cough may serve as an early indicator of respiratory inflammation and potential disease risk, the association between ECIGs use and cough raises potential concerns.