Optimization of Antioxidant Activity of Compounds Generated during Ginseng Extract Fermentation Supplemented with Lactobacillus.

Ginseng holds high medicinal and cosmetic value, with stem and leaf extracts garnering attention for their abundant bioactive ingredients. Meanwhile, fermentation can enhance the effectiveness of cosmetics. The aim of this study was to optimize ginseng fermentation to produce functional cosmetics. Ginseng stem and leaf extracts were fermented with five different strains of lactic acid bacteria. Using 2,2-diphenyl-1-picrylhydrazyl (DPPH), hydroxyl radical (·OH), and superoxide anion (O2·-) scavenging activities as indicators, the fermentation process was optimized via response surface methodology. Finally, validation of the antioxidant activity of the optimized fermentation broth was performed using human skin cells (HaCaT and BJ cells). Based on the antioxidant potency composite comprehensive index, Lactiplantibacillus plantarum 1.140 was selected, and the optimized parameters were a fermentation time of 35.50 h, an inoculum size of 2.45%, and a temperature of 28.20 °C. Optimized fermentation boosted antioxidant activity: DPPH scavenging activity increased by 25.00%, ·OH by 94.00%, and O2·- by 73.00%. Only the rare ginsenoside Rg5 showed a substantial rise in content among the 11 ginsenosides examined after fermentation. Furthermore, the flavonoid content and ·OH scavenging activity were significantly negatively correlated (r = -1.00, p < 0.05), while the Rh1 content and O2·- scavenging activity were significantly positively correlated (r = 0.998, p < 0.05). Both the 0.06% (v/v) and 0.25% (v/v) concentrations of the optimized broth significantly promoted cell proliferation, and notable protective effects against oxidative damage were observed in HaCaT cells when the broth was at 0.06%. Collectively, we demonstrated that ginseng fermentation extract effectively eliminates free radicals, preventing and repairing cellular oxidative damage. This study has identified new options for the use of fermented ginseng in functional cosmetics.

Lesion size as a prognostic factor in the antifungal treatment of pulmonary cryptococcosis: a retrospective study with chest CT pictorial review of 2-year follow up.

BACKGROUND: Pulmonary cryptococcosis (PC) is a fungal infection that can have a variable prognosis depending on several factors. The objective of this study was to analyse the characteristics of pulmonary lesions and identify prognostic factors in patients with PC who were human immunodeficiency virus (HIV) -negative and underwent antifungal treatment. METHODS: The study enrolled patients diagnosed with PC who were negative for HIV. Symptoms, CT characteristics of pulmonary lesions, serum cryptococcal capsular antigen (CrAg) titre, underlying diseases, and duration of antifungal treatment were evaluated over a 2-year follow-up. RESULTS: A total of 63 patients (40 men and 23 women) with a mean age of 50.4 years were included. Half of the patients (50.8%) were asymptomatic, and the most common symptoms were cough (44.4%), expectoration (27.0%), and fever (17.5%). Pulmonary lesions were mainly present in the peripheral and lower lobes of the lung, with 35 cases classified as nodular-type lesions and 28 cases classified as mass-type lesions. At the first, third, sixth, 12th, and 24th-month follow-ups, the median proportion of residual pulmonary lesions were 59.6%, 29.9%, 12.2%, 9.6%, and 0.0%, respectively. During antifungal treatment, the lesions of 33 patients achieved complete response, while the remaining 30 patients did not. Compared with the non-CR group, the CR group had a lower baseline serum CrAg titre (median, 1:20 vs 1:80, P < 0.01), smaller pulmonary lesion size (median area, 1.6 cm2 vs 6.3 cm2, P < 0.01), lower Hounsfield-units (HU) radiodensity (median, - 60.0 HU vs - 28.5 HU, P < 0.05), more nodular-type lesions (72.7% vs 36.7%, P < 0.01), and fewer air-bronchogram signs (18.2% vs 43.3%, P < 0.05). Multivariate logistic regression analysis showed that a larger lesion size on chest CT scans was associated with a lower likelihood of achieving complete response [OR: 0.89; 95% CI (0.81-0.97); P < 0.05]. CONCLUSIONS: PC was more commonly observed in HIV-negative men, and chest CT scans mostly revealed nodular-type lesions. After antifungal treatment, patients with smaller lesions had a better prognosis.

Gene expression profiles of mRNA, lncRNA, miRNA, and circRNA and their clinical implications in chronic rhinosinusitis with nasal polyps.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory disease with complex pathophysiology and therapeutic strategies. Moreover, the molecular mechanisms underlying the pathogenesis of CRSwNP are incompletely understood. OBJECTIVE: This study aimed to investigate the transcriptomic characteristics, ceRNA networks, and whether these molecular markers play a role in the occurrence and development of CRSwNP. METHODS: Following RNA sequencing, a ceRNA network was predicted and constructed based on the sequencing results and multiple databases. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and disease ontology (DO) were applied to analyze the potential mechanisms in relation to the pathogenesis of CRSwNP. CIBERSORT was used to evaluate the immune cell infiltration levels in CRSwNP. The candidate genes of differentially expressed (DE) mRNA, DE-lncRNA, DE-miRNA, and DE-circRNA were verified by RT-qPCR, and the back-splice junction of circRNA was verified using Sanger sequencing. The clinical significance of differentially expressed genes was analyzed with correlation test and receiver operating characteristic curve. RESULTS: We identified 716 DE-mRNA, 230 DE-lncRNA, 42 DE-miRNA, and 46 DE-circRNA, and GO and KEGG enrichment analyses indicated that they were involved in multiple biological pathways, predominantly those associated with immunity and inflammation. DO analysis revealed CRSwNP is associated with diseases such as gastroesophageal reflux and allergic reactions. High expression of circ_0021727 was significantly and positively correlated with several important clinical indicators, and the area under the curve was 0.741. CONCLUSIONS: This study provides transcriptomic characteristics, which are potential biomarkers or therapeutic targets for the diagnosis and treatment of CRSwNP.

Private supplementary education and Chinese adolescents' development: The moderating effects of family socioeconomic status.

Using the data from the China Education Panel Survey (CEPS), this study estimated the effects of two types of private supplementary education, namely, cram school and hobby class, on the development of Chinese junior high school students and the moderating effects of family socioeconomic status (SES). First, we found that cram schools and hobby classes both positively correlate with some dimensions of adolescents' development while negatively correlating with others. Attending cram schools is positively associated with students' academic achievement but negatively related to their noncognitive skills. Participating in hobby classes is positively associated with noncognitive abilities but negatively related to cognitive abilities. Second, the negative correlations between cram schools and noncognitive abilities and between hobby classes and cognitive abilities are stronger for low-SES students than their affluent counterparts. The current study's findings shed new light on the role of private supplementary education in educational inequality and social stratification in China.

Income inequality, cultural capital, and high school students' academic achievement in OECD countries: A moderated mediation analysis.

This study examines how social context, in this case, income inequality, shapes the role of cultural capital in educational success. First, we revisit the associations between (objectified) cultural capital and academic achievement, and cultural capital's role in mediating the relationship between family SES and academic achievement. More importantly, we explore how national-level income inequality moderates these two relationships. By analyzing a multilevel dataset of 32 OECD countries, a combination of PISA 2018 data and several national indexes, we find that: (1) cultural capital not only has a positive association with students' academic achievement but also acts as a significant mediator of the relationship between family SES and academic achievement in OECD countries; (2) both cultural capital's association with academic achievement and it's mediating role are stronger in more equal countries than in unequal ones. The findings shed new light on understanding how cultural capital shapes intergenerational education inequality across countries with different levels of inequality.

Endoscopic dacryocystorhinostomy for refractory nasolacrimal duct obstruction with a small lacrimal sac (≤ 5 mm in diameter).

BACKGROUND: Although endoscopic dacryocystorhinostomy (DCR) is a standard procedure for nasolacrimal duct obstruction (NLDO), the failure rate remains approximately 10%. A small lacrimal sac is considered the main reason for surgical failure. We explored the efficacy of endoscopic DCR for the treatment of NLDO with a small lacrimal sac. METHODS: The clinical data of 72 patients (88 eyes) diagnosed with NLDO and undergoing endoscopic DCR from 2012 to 2020, with at least 24 months of follow-up were retrospectively collected. Intraoperatively, the Rosenmüller valves were fully exposed, mucosal flaps were preserved to cover the naked bone, and a silicone tube was implanted if necessary. Postoperative intervention was performed if necessary. The main outcome measures were symptomatic improvement and objective ostium patency. RESULTS: Eighty-eight eyes of 72 patients were divided into two groups: the refractory group (34 patients, 47 eyes), with a small lacrimal sac (≤ 5 mm in diameter), and the simple group (38 patients, 41 eyes). Patients with small lacrimal sacs were more prone to bilateral eye disease than those in the simple group (P = 0.014) and required a longer postoperative follow-up (P < 0.001). Refractory NLDO and simple NLDO had a success rate of 91.5% and 95.1%, respectively, with no significant difference. CONCLUSION: Endoscopic DCR for refractory NLDO with a small lacrimal sac could achieve a beneficial result by exposing the Rosenmüller valves, preserving mucosal flaps, implanting necessary intubation, and intervening postoperatively. Thus, a small lacrimal sac should not be regarded as a contraindication to surgery.

Computed Tomography Analysis of the Anterosuperior Portion of the Bulla Lamella in Chinese Subjects and Its Surgical Significance in Endoscopic Frontal Sinusotomy.

INTRODUCTION: The anterosuperior portion of the bulla lamella can extend into the frontal sinus and form the supra bulla frontal cell (SBFC) and supraorbital ethmoid cell (SOEC). This can affect the frontal drainage pathway and make surgery more challenging. OBJECTIVES: The aim of the study was to compare the anatomical characteristics of SBFC and SOEC in Chinese chronic rhinosinusitis (CRS) patients and explore the relationship between the cells and frontal sinusitis (FS). The surgical skills in dealing with these cells were also studied. METHODS: We prospectively identified SBFC and SOEC in 114 patients with CRS by computed tomography (CT). The sides of the patients were divided into groups A (with FS) and B (without FS). CT scans were analyzed to distinguish the SBFC, SOEC, and the drainage pathway. Statistical analysis was conducted to determine whether the cells were associated with the occurrence of FS. RESULTS: The prevalence of frontal cells was as follows: SBFC: 9.65%, SOEC: 21.93%. There was an association between the presence of SBFC and FS (p < 0.05). The anterior drainage pathway was present in patients with SBFC and SOEC, anterolateral pathway in those with SBFC/SOEC coexisting with the frontal septal cell, and anteromedial pathway in those with SBFC/SOEC coexisting with the supra agger frontal cell. CONCLUSIONS: There was an association between the presence of SBFC and the occurrence of FS. Extension of the anterosuperior portion of the bulla lamella into the frontal sinus obstructed the drainage pathway posteriorly. Understanding the anatomy may help surgeons thoroughly dissect the bulla lamella.

Prevalence and Distribution of Electronic Cigarette Use Before and During Pregnancy Among Women in 38 States of the United States.

INTRODUCTION: To examine the prevalence and the changing pattern of e-cigarette use from preconception to pregnancy. AIMS AND METHODS: This is a cross-sectional study using data from the multi-site Pregnancy Risk Assessment Monitoring System in the United States, 2016-2017. All participating mothers with information on e-cigarette use before and during pregnancy were included. Self-reported information about e-cigarette use were assessed using questionnaires. Weighted prevalences of e-cigarette use before and during pregnancy were calculated. Multivariable logistic regressions were used to examine the association between various demographic characteristics and e-cigarette use before or during pregnancy. RESULTS: This study included 69 508 pregnant women from 38 states in the United States. The weighted prevalence of e-cigarette use before pregnancy and during the last 3 months of pregnancy was 3.6% (95% confidence interval [CI] 3.4%-3.9%) and 1.1% (0.9%-1.2%), respectively. The prevalence varied across states, ranging from 1.3% to 8.3% for e-cigarette use before pregnancy and from 0.1% to 3.4% for e-cigarette use during the last 3 months of pregnancy. Among women who used e-cigarettes before pregnancy, 24.4% (21.7%-27.1%) continued to use e-cigarettes during pregnancy. Among women who used e-cigarettes during pregnancy, 62.3% (56.5%-68.0%) were dual users. In multivariable analyses, cigarette smoking was most strongly associated with e-cigarette use. The adjusted odds ratio comparing smokers with nonsmokers before pregnancy was 11.10 (95% CI 9.34-13.20) for e-cigarette use before pregnancy and 6.72 (95% CI 4.38-10.31) for e-cigarette use during pregnancy. CONCLUSIONS: Using data from 38 states in the United States, we showed geographical variations in the prevalence of e-cigarette use before and during pregnancy. Among women who used e-cigarettes before pregnancy, a quarter of them continued to use e-cigarettes during pregnancy. Conventional cigarette use is a strong risk factor for e-cigarette use before and during pregnancy. The prevalence of e-cigarette use needs to be monitored continuously. IMPLICATIONS: This study provides important information to understand the status and changing patterns of e-cigarette use in pregnant women in the United States. Among pregnant women in 38 states in the United States, 3.6% of them used e-cigarettes during the 3 months before pregnancy and 1.1% used them during the last 3 months of pregnancy. The prevalence varied across states. A quarter of women who used e-cigarettes before pregnancy continued to use e-cigarettes during pregnancy. Cigarette smoking is the strongest predictor of e-cigarette use. Future research about health effects of e-cigarette use during pregnancy is in urgent need.

Correction to: Efficacy and safety of delivery of topical medication on to the frontal sinus at different head positions after frontal sinusotomy.

In the original publication of the article, under the experimental protocol of the section "Clinical head position study in postoperative CRS patients", the following sentence "There were 20 CRS patients, 12 male and 8 female across an age range of 19-64 years…" was published incorrectly.

Efficacy and safety of delivery of topical medication on to the frontal sinus at different head positions after frontal sinusotomy.

PURPOSE: Effective topical medications delivery to the frontal sinus is crucial to recovery from frontal sinusotomy. However, finding a way to deliver local medications to the frontal sinus is still a major challenge. The objective of this study was to evaluate the influence of various head positions on postoperative frontal sinus drug deposition. The safety and efficacy were also evaluated in postoperative chronic rhinosinusitis (CRS) patients. METHODS: Full house surgery was performed on six fresh frozen cadaver heads. The fluorescein solution was dropped into the nasal sinuses in three different head positions, and the fluorescein deposition was evaluated. A prospective cohort study was performed to validate the results in 20 postoperative CRS patients. The cortisol level, symptom VAS and the frontal recess endoscopy scores were evaluated pre- and postoperatively. RESULTS: The frontal recess delivery of fluorescein was better in the Mygind and vertex-to-floor positions than in the head back position. The cortisol level of patients dropped markedly after taking oral methylprednisolone, but returned to baseline when replaced with budesonide drops. The pre- and postoperative symptom VAS scores did not differ significantly between the two groups. Endoscopic scores of the vertex-to-floor group were significantly better than those of the Mygind group. CONCLUSION: Both the Mygind and the vertex-to-floor head positions were optimal for delivery of topical medications to the frontal recess. When applying the steroid drops, both positions were found to be safe and associated with effective relief of symptoms. The vertex-to-floor position can better improve the endoscopic scores of frontal recess and frontal sinus.

Cuproptosis-associated genes (CAGs) contribute to the prognosis prediction and potential therapeutic targets in hepatocellular carcinoma.

BACKGROUND: Cuproptosis is a novel form of cell death that exhibits close association with mitochondrial respiration and occurs through distinct mechanisms compared to previously characterized forms of cell death. However, the precise impact of cuproptosis-associated genes (CAGs) on prognosis, immune profiles, and treatment efficacy in hepatocellular carcinomas (HCC) remains poorly understood. METHODS: A comprehensive analysis of CAGs in hepatocellular carcinoma (HCC) prognosis was conducted using genomic data from HCC patients. Consensus clustering analysis was performed to determine molecular subtypes related to cuproptosis in HCC. The single-sample gene set enrichment analysis (ssGSEA) algorithm was applied to quantify the infiltration levels of immune cells, while the "ESTIMATE" package was employed to calculate tumor purity, stromal scores, and immune scores in the tumor microenvironment (TME). Principal component analysis (PCA) algorithm was utilized to construct a risk score related to CAGs. Finally, CCK8, wound healing, Transwell migration/invasion, EDU and xenograft model were employed to explore the potential oncogenic role of MTF1. RESULTS: Three distinct patterns of cuproptosis modification were identified, each associated with unique functional enrichments, clinical characteristics, immune cell infiltration, immune checkpoints, tumor microenvironment (TME), and prognosis. A CAGs-related risk score (Cuscore) was developed to predict prognosis in TCGA and validated in GSE76427 and ICGC datasets. Notably, patients with a low Cuscore had better prognoses and were more likely to benefit from immunotherapy.Additionally, the high Cuscore group in HCC also revealed three potential therapeutic targets (TUBA1B, CDC25B, and CSNK2A1) as well as several therapeutic compounds. Moreover, the experiment measured the expression levels of six prognosis-related CAGs, wherein knockdown of MTF1 exhibited suppression of proliferation, invasion, and migration formation in HCC cell lines. CONCLUSION: The findings have enhanced our comprehension of the cuproptosis characteristics in HCC, and stratification based on CuScore may potentially enhance the prediction of patients' prognosis and facilitate the development of effective and innovative treatment strategies.

The association between polyunsaturated fatty acids and chronic obstructive pulmonary disease: a meta-analysis.

Background: Chronic obstructive pulmonary disease (COPD) is a common respiratory disease, and its development and prognosis are influenced by many nutrients. However, the relationship between polyunsaturated fatty acids (PUFAs) and COPD remains unclear. Methods: This study searched all literature reports on PUFAs and COPD based on electronic databases from their inception up to October 2023. Meta-analysis was conducted to evaluate the differences in PUFAs between COPD patients and controls, the risk of COPD in subjects with different levels of PUFA concentrations, and the effect of PUFA supplementation on COPD. Results: A total of nineteen studies met our inclusion criteria, which included 155 636 subjects. Our meta-analysis results showed that the daily dietary intake of PUFAs was lower in COPD patients than in controls (SMD = -0.80 g, 95% CI: -1.28, -0.31 g, I2 = 98.6%, P < 0.001). Meanwhile, the lower n-3 PUFA levels and higher n-6 PUFA levels were associated with an increased risk of COPD (effect size n-3 = 0.87, 95% CI: 0.77, 0.98, I2 = 52.2%, P = 0.018; effect size n-6 = 1.23, 95% CI: 1.05, 1.43, I2 = 75.2%, P < 0.001). Furthermore, the content of low-density lipoprotein cholesterol in the PUFA supplementation group was higher than that in the control group (SMD = 0.63 mg dL-1, 95% CI: 0.15, 1.12 mg dL-1, I2 = 0.0%, P = 0.697). Conclusions: Our meta-analysis indicated a potential relationship between PUFAs and COPD. More large-scale prospective cohort studies and clinical trials are necessary to validate this relationship.

Association of methyl donor nutrients dietary intake and sleep disorders in the elderly revealed by the intestinal microbiome.

Currently, sleep disorders (SD) in the elderly are gaining prominence globally and are becoming a significant public health concern. Methyl donor nutrients (MDNs), such as vitamin B6, vitamin B12, folate, and choline, have been reported to have the potential to improve sleep disorders. Moreover, MDNs help to maintain gut flora homeostasis, and are closely associated with the development of SD. Nevertheless, there has been a lack of comprehensive human studies examining the association between MDNs intake and SD. In our study, we comprehensively evaluated the association between MDNs intake and SD in the elderly and used 16S rRNA gene sequencing to explore the underlying mechanism. We found that the SD group (n = 91) had a lower methyl-donor nutritional quality index (MNQI) and a trend toward lower intake compared to the control group (n = 147). Based on the intestinal microbiome, the beta diversity of the intestinal flora was higher in the high methyl-donor nutritional quality (HQ) group compared to the low methyl-donor nutritional quality (LQ) group, and it was lower in the SD group compared to the control group. This suggests that MDNs may regulate sleep by modulating the abundance distribution of the microbiota. Subsequently, we performed correlation analyses between the relative abundance of the microbiota, MDNs intake, and the Pittsburgh Sleep Quality Index (PSQI), identifying five genera with potential regulatory roles. The KEGG pathway analysis indicated that energy metabolism and one-carbon metabolism might be the pathways through which MDNs modulate sleep. This study offers dietary guidance strategies for managing SD in the elderly and provides insights for targeted microbiota intervention.

Association of Methyl Donor Nutrients' Dietary Intake and Cognitive Impairment in the Elderly Based on the Intestinal Microbiome.

Globally, cognitive impairment (CI) is the leading cause of disability and dependency among the elderly, presenting a significant public health concern. However, there is currently a deficiency in pharmacological interventions that can effectively cure or significantly reverse the progression of cognitive impairment. Methyl donor nutrients (MDNs), including folic acid, choline, and vitamin B12, have been identified as potential enhancers of cognitive function. Nevertheless, there remains a dearth of comprehensive research investigating the connection between the dietary intake of MDNs and CI. In our study, we comprehensively assessed the relationship between MDNs' dietary intake and CI in older adults, utilizing 16S rRNA gene sequencing to investigate the potential underlying mechanisms. The results showed an obvious difference in the methyl-donor nutritional quality index (MNQI) between the dementia (D) group and the dementia-free (DF) group. Specifically, there was a lower MNQI in the D group than that in the DF group. For the gut microbiome, the beta diversity of gut flora exhibited higher levels in the high methyl-donor nutritional quality (HQ) group as opposed to the low methyl-donor nutritional quality (LQ) group, and lower levels in the D group in comparison to the DF group. Subsequently, we performed a correlation analysis to examine the relationship between the relative abundance of microbiota, the intake of MDNs, and Montreal Cognitive Assessment (MoCA) scores, ultimately identifying ten genera with potential regulatory functions. Additionally, KEGG pathway analyses suggested that the one-carbon metabolism, chronic inflammation, and DNA synthesis potentially serve as pathways through which MDNs may be promising for influencing cognitive function. These results implied that MDNs might have the potential to enhance cognitive function through the regulation of microbiota homeostasis. This study offers dietary recommendations for the prevention and management of CI in the elderly.

Targeting Aging and Longevity with Exogenous Nucleotides (TALENTs): Rationale, Design, and Baseline Characteristics from a Randomized Controlled Trial in Older Adults.

Nucleotides (NTs), important biomolecules involved in numerous cellular processes, have been proposed as potential candidates for anti-aging interventions. However, whether nucleotides can act as an anti-aging supplement in older adults remains unclear. TALENTs is a randomized, double-blinded, placebo-controlled trial that evaluates the efficacy and safety of NTs as an anti-aging supplement in older adults by exploring the effects of NTs on multiple dimensions of aging in a rigorous scientific setting. Eligible community-dwelling adults aged 60-70 years were randomly assigned equally to two groups: nucleotides intervention group and placebo control group. Comprehensive geriatric health assessments were performed at baseline, 2-months, and 4-months of the intervention. Biological specimens were collected and stored for age-related biomarker testing and multi-omics sequencing. The primary outcome was the change from baseline to 4 months on leukocyte telomere length and DNA methylation age. The secondary aims were the changes in possible mechanisms underlying aging processes (immunity, inflammatory profile, oxidative stress, gene stability, endocrine, metabolism, and cardiovascular function). Other outcomes were changes in physical function, body composition and geriatric health assessment (including sleep quality, cognitive function, fatigue, frailty, and psychology). In the RCT, 301 participants were assessed for eligibility and 122 were enrolled. Participants averaged 65.65 years of age, and were predominately female (67.21%). All baseline characteristics were well-balanced between groups, as expected due to randomization. The majority of participants were pre-frailty and had at least one chronic condition. The mean scores for physical activity, psychological, fatigue and quality of life were within the normal range. However, nearly half of the participants still had room for improvement in cognitive level and sleep quality. This TALENTs trial will represent one of the most comprehensive experimental clinical trials in which supplements are administered to elderly participants. The findings of this study will contribute to our understanding of the anti-aging effects of NTs and provide insights into their potential applications in geriatric healthcare.

Comprehensive analysis reveals hub genes associated with immune cell infiltration in allergic rhinitis.

Objectives: Allergic rhinitis (AR) refers to a form of respiratory inflammation that mainly affects the sinonasal mucosa. The purpose of this study was to explore the level of immune cell infiltration and the pathogenesis of AR. Methods: We performed a comprehensive analysis of two gene expression profiles (GSE50223 and GSE50101, a total of 30 patients with AR and 31 healthy controls). CIBERSORT was used to evaluate the immune cell infiltration levels. Weighted gene coexpression network analysis was applied to explore potential genes or gene modules related to immune status, and enrichment analyses including gene ontology, Kyoto Encyclopedia of Genes and Genomes, gene set enrichment analysis, and gene set variation analysis, were performed to analyze the potential mechanisms in AR. A protein-protein interaction network was constructed to investigate the hub genes, and consensus clustering was conducted to identify the molecular subtypes of AR. Results: Compared to the healthy controls, patients with AR had high abundance levels and proportions of CD4+ memory-activated T cells. One hundred and eight immune-related differentially expressed genes were identified. Enrichment analysis suggested that AR was mainly related to leukocyte cell-cell adhesion, cytokine-cytokine receptor interaction, T-cell activation, and T-cell receptor signaling pathway. Ten hub genes, including TYROBP, CSF1R, TLR8, FCER1G, SPI1, ITGAM, CYBB, FCGR2A, CCR1, and HCK, which were related to immune response, might be crucial to the pathogenesis of AR. Three molecular subtypes with significantly different immune statuses were identified. Conclusion: This study improves our understanding of the molecular mechanisms in AR via comprehensive strategies and provides potential diagnostic biomarkers and therapeutic targets of AR.

Decoupling locally enhanced electric field treatment (LEEFT) intensity and copper release by applying asymmetric electric pulses for water disinfection.

Copper has well-known anti-microbial properties but is typically not considered for drinking water disinfection because of its health risk to human at efficient biocidal concentrations. Locally enhanced electric field treatment (LEEFT) is a cutting-edge technique that aims to inactivate bacteria by generating aqueous pores on the cell membrane through the application of a strong electric field. LEEFT can also increase the permeability of the cell membrane, which promotes the uptake of chemical disinfectants to reduce the required biocidal concentrations. Previously, a coaxial-electrode copper ionization cell (CECIC) was developed to combine copper disinfection with LEEFT, demonstrating superior disinfection efficiency with low effluent copper concentrations (<0.5 mg/L). However, using direct-current (DC) voltages results in a dilemma that a higher voltage is necessary for effective LEEFT disinfection, but a lower voltage is required to limit Cu release. Here, asymmetric electric pulses are employed to decouple the LEEFT intensity from copper release in the CECIC. In this case, LEEFT intensity is primarily determined by the pulse amplitude while the copper release is controlled by the pulse offset. We have demonstrated that the use of asymmetric electric pulses achieves significantly higher inactivation efficiency compared to the DC voltages with the similar level of Cu release. For the water with conductivity similar to tap water (∼100 µS/cm), a high inactivation efficiency of 4.7-log is achieved with only 0.49 mg/L copper release. These findings highlight the potential of asymmetric electric pulses as a promising alternative to DC voltages for the practical application of LEEFT-Cu systems in the future.

Meal Skipping and Shorter Meal Intervals Are Associated with Increased Risk of All-Cause and Cardiovascular Disease Mortality among US Adults.

BACKGROUND: Previous dietary studies and current dietary guidelines have mainly focused on dietary intake and food patterns. Little is known about the association between eating behaviors such as meal frequency, skipping and intervals, and mortality. OBJECTIVE: The objective was to examine the associations of meal frequency, skipping, and intervals with all-cause and cardiovascular disease (CVD) mortality. DESIGN: This was a prospective study. PARTICIPANTS/SETTING: A total of 24,011 adults (aged ≥40 years) who participated in the National Health and Nutrition Examination Survey 1999-2014 were included in this study. Eating behaviors were assessed using 24-hour recall. Death and underlying causes of death were ascertained by linkage to death records through December 31, 2015. MAIN OUTCOME MEASURES: The outcomes were all-cause and CVD mortality. STATISTICAL ANALYSES PERFORMED: Multivariable Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs) of all-cause and CVD mortality. RESULTS: During 185,398 person-years of follow-up period, 4,175 deaths occurred, including 878 cardiovascular deaths. Most participants ate three meals per day. Compared with participants eating three meals per day, the multivariable-adjusted HRs for participants eating one meal per day were 1.30 (95% CI 1.03 to 1.64) for all-cause mortality, and 1.83 (95% CI 1.26 to 2.65) for CVD mortality. Participants who skipped breakfast have multivariable-adjusted HRs 1.40 (95% CI 1.09 to 1.78) for CVD mortality compared with those who did not. The multivariable-adjusted HRs for all-cause mortality were 1.12 (95% CI 1.01 to 1.24) for skipping lunch and 1.16 (95% CI 1.02 to 1.32) for skipping dinner compared with those who did not. Among participants eating three meals per day, the multivariable-adjusted HR for participants with an average interval of ≤4.5 hours in two adjacent meals was 1.17 (95% CI 1.04 to 1.32) for all-cause mortality, comparing with those having a meal interval of 4.6 to 5.5 hours. CONCLUSIONS: In this large, prospective study of US adults aged 40 years or older, eating one meal per day was associated with an increased risk of all-cause and CVD mortality. Skipping breakfast was associated with increased risk of CVD mortality, whereas skipping lunch or dinner was associated with increased risk of all-cause mortality. Among participant with three meals per day, a meal interval of ≤4.5 hours in two adjacent meals was associated with higher all-cause mortality.

Leveraging 3D Bioprinting and Photon-Counting Computed Tomography to Enable Noninvasive Quantitative Tracking of Multifunctional Tissue Engineered Constructs.

3D bioprinting is revolutionizing the fields of personalized and precision medicine by enabling the manufacturing of bioartificial implants that recapitulate the structural and functional characteristics of native tissues. However, the lack of quantitative and noninvasive techniques to longitudinally track the function of implants has hampered clinical applications of bioprinted scaffolds. In this study, multimaterial 3D bioprinting, engineered nanoparticles (NPs), and spectral photon-counting computed tomography (PCCT) technologies are integrated for the aim of developing a new precision medicine approach to custom-engineer scaffolds with traceability. Multiple CT-visible hydrogel-based bioinks, containing distinct molecular (iodine and gadolinium) and NP (iodine-loaded liposome, gold, methacrylated gold (AuMA), and Gd2 O3 ) contrast agents, are used to bioprint scaffolds with varying geometries at adequate fidelity levels. In vitro release studies, together with printing fidelity, mechanical, and biocompatibility tests identified AuMA and Gd2 O3 NPs as optimal reagents to track bioprinted constructs. Spectral PCCT imaging of scaffolds in vitro and subcutaneous implants in mice enabled noninvasive material discrimination and contrast agent quantification. Together, these results establish a novel theranostic platform with high precision, tunability, throughput, and reproducibility and open new prospects for a broad range of applications in the field of precision and personalized regenerative medicine.

Efficacy and Safety of Ganduqing Granules in Treating the Common Cold: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial.

Background: There is no clear evidence-based medicine that points to the most effective drug treatments for the common cold. In view of its ability to relieve symptoms and shorten the disease course, as well as its minimal side effects, traditional Chinese medicine (TCM) has been widely used to treat the common cold. However, there is a lack of strong evidence to support the clinical efficacy of TCM. This study aimed to evaluate the efficacy and safety of Ganduqing granules in the treatment of the common cold based on the network pharmacology analysis. Methods: In this multicenter, randomized, double-blind, placebo-controlled trial, 60 eligible subjects will be randomly assigned to either the intervention group or the placebo group. The intervention group will be treated with Ganduqing granules, while the placebo group will be treated with placebo. After 5 days of intervention, the efficacy and safety of Ganduqing granules in the treatment of the common cold will be observed. The primary outcome is the time to clearance of all symptoms. The secondary outcomes included the levels of IL-6, TNF-α, SOD, and MDA in the peripheral blood, time to disappearance of primary symptoms and secondary symptoms, clinical symptom remission rate, and change in TCM syndrome score. Results: Sixty participants completed the study. Ganduqing granules showed a greater effect on the time to clearance of all symptoms (P < 0.0001), nasal discharge (P=0.0124), fatigue and lack of strength (P=0.0138), dryness of the pharynx (P < 0.0001), pharyngalgia or dysphagia (P < 0.0001), and expectoration (P < 0.0431) compared with the placebo group. Participants in the intervention group had a greater decrease of IL-6 levels compared with the placebo group (P < 0.007); similar results were observed for the SOD (P < 0.033). However, the change in TNF-α and MDA levels in the intervention group was not significantly different from the placebo group. In addition, participants in the intervention group had a greater decrease of TCM syndrome score compared with the placebo group (P < 0.040). Conclusion: Ganduqing granules could improve common cold symptoms, shorten the disease course, attenuated inflammation and oxidative stress, and provided objective evidence for the efficacy and safety of a Chinese herbal medicine in treating the common cold.