Search Results (20)

Background: Elderly patients with chronic lower respiratory diseases (CLRDs) demonstrate an increased susceptibility to complications arising from influenza. Influenza vaccination remains the most effective strategy against influenza-related diseases among elderly CLRD patients. This study aimed to evaluate the influenza vaccination status of older CLRD patients and the factors affecting influenza vaccination. Methods: Using population-based health registries, we analyzed the longitudinal uptake of influenza vaccination among elderly patients with CLRDs in Ningbo from the 2018/19 season to the 2022/23 season. A multivariate logistic regression analysis was performed to identify behavioral determinants influencing influenza vaccination among elderly CLRD patients under Ningbo’s post-pandemic free vaccination policy. Results: An average of 487,309 older patients with CLRDs were included in our analysis for each season. The influenza vaccination rate increased from 3.59% in 2018/19 to 43.32% in the 2022/23 influenza season. There was a significant increase in the proportion of timely influenza vaccinations prior to November 15, rising from 3.01% before the COVID-19 pandemic to 33.90% during the pandemic period. The multivariate logistic regression analysis indicated that both the COVID-19 pandemic and free vaccination policy significantly promoted influenza vaccine uptake. Older CLRD patients with comorbidities such as diabetes, hypertension, or cancer exhibited higher influenza vaccination coverage, whereas those who have experienced acute cardiovascular events showed a lower vaccination rate. Additionally, a prior vaccination history significantly influenced uptake. Conclusions: Despite the significant improvement in vaccination rates, coverage among elderly patients with CLRDs remains below the WHO target. Addressing this gap requires integrated interventions that combine expanding the population eligible for free vaccinations, community mobilization efforts, and effective communication regarding cardiovascular safety to mitigate vaccine hesitancy within high-risk groups. Full article

Trimethylamine N-oxide (TMAO), a gut microbiome metabolite linked to cardiovascular health, can be influenced by dietary factors like choline intake and diet quality. This study compared the effects of mixed tree nuts (MTNs) and pretzels, as part of a 12-week hypocaloric weight loss diet, on TMAO levels and identified dietary predictors. Methods: Plasma samples from 95 overweight individuals consuming either 1.5 oz. of mixed tree nuts (MTNs, n = 56) or isocaloric pretzels (n = 39) daily for 12 weeks were analyzed. Nutritional data were collected at baseline and week 12 through dietary recall using the Automated Self-Administered 24 h Dietary Assessment Tool (ASA24), and the overall diet quality was assessed via the Healthy Eating Index (HEI) score. TMAO levels were determined and analyzed using linear mixed-effect models, adjusting for covariates. Wilcoxon signed-rank tests compared baseline and week 12 TMAO and weight. Multiple linear regression identified baseline predictors of TMAO. Results: Baseline demographics, anthropometric measures, HEI scores, and dietary choline intake were similar between the MTN and pretzel groups. A significant positive association was observed between baseline dietary choline and plasma TMAO levels (p = 0.012). The 12-week hypocaloric diet led to significant weight reduction in both groups (p < 0.01), but the magnitude of weight loss did not differ significantly between the MTN (−3.47 lbs) and pretzel (−4.25 lbs) groups (p = 0.18). Plasma TMAO levels decreased significantly in both groups (p < 0.01), but the between-group difference in reduction was not significant. (MTNs: −0.34 vs. pretzels: −0.37; p = 0.43). HEI scores and dietary choline intake remained unchanged, with no significant time–intervention interaction. Participants with low baseline HEI scores (≤53.72) had a more pronounced reduction in TMAO levels in the MTN group compared to the pretzel group (MTN: −0.54 vs. pretzel: −0.23; p = 0.045) over 12 weeks, despite similar weight loss. This difference was not observed in participants with higher HEI scores. Conclusions: The 12-week hypocaloric diet reduced body weight and plasma TMAO levels similarly in both MTN and pretzel groups. Participants with lower dietary quality saw a greater reduction in TMAO levels in the MTN group, suggesting MTNs may better modulate TMAO levels, especially for those with poorer baseline diets. Full article

Cancer is a major cause of death worldwide, and vaccine administration is an effective way to stimulate immune responses in patients and to achieve preventive and therapeutic effects. Few vaccines have been used in clinical settings because they have poor immunogenicity, and it is difficult to induce a robust immune response in patients. An adjuvant is an important component of a vaccine that can enhance the intensity, speed, and duration of immune responses. The achievements of adjuvants in the production of stable, safe, and immunogenic tumor vaccines have aroused the enthusiasm of researchers. Recent results have suggested that plant-derived adjuvants have unique advantages, such as greatly improving immune responses to cancer vaccines and promoting humoral and cellular immunity with good biocompatibility and biodegradability. When these adjuvants are used in combination with vaccines, they can not only activate the immune response in vivo but can also promote cytokine secretion and accelerate dendritic cell maturation. This review focused on the application progress of plant adjuvants, including saponins, polysaccharides, flavonoids, and plant virus-like particles, and their combination with nano-delivery systems in cancer vaccines. At the same time, we have also discussed the immunomodulatory mechanisms of these adjuvants and their prospects for improving vaccine efficacy in the treatment of cancer in the future. These promising plant adjuvants may provide prospects and a research basis for the development of tumor vaccines. Full article

Background: Melanoma is one of the most common malignancies, posing a significant health threat to patients, particularly in advanced stages due to its high aggressiveness. Chemotherapy agents with biocompatibility and low susceptibility to induce resistance are required for systematic management. Methods: Dendrimer-derived mimics (DMs) of host defense peptides (HDPs), which were constructed by a dendrimer core and optimized ratios of the hydrophobic arm, were used to treat A375 cells and HaCaT cells as the control. Live/dead staining, flow cytometry, and scanning electron microscopy (SEM) were conducted to analyze the anticancer mechanism. Mice with subcutaneous tumors were used to test the antitumor activity and toxicity in vivo. Results: DMs exhibited enhanced activity against A375 cells with remarkable selectivity, which mimics the action of natural HDPs and can cause damage to cell membranes. DMs can effectively inhibit solid tumor growth with minimal systemic toxicity and no adverse effects on healthy tissues. Conclusion: All the findings highlight DMs as promising anticancer candidates with significant potential for systemic melanoma therapy. Full article

Background: Although breastfeeding has been extensively documented to confer health benefits to infants in the early stages of their lives, the sustained influence that it has on autistic traits throughout childhood remains unclear. This study endeavors to explore the correlation between the length of exclusive breastfeeding, the overall duration of breastfeeding, and the manifestation of autistic traits in Chinese children. Methods: A cross-sectional study was conducted among 17,382 three-year-olds residing in Longhua District, Shenzhen, China. The participants’ socio-economic status, breastfeeding patterns, and autistic traits were recorded using questionnaires. Breastfeeding durations were analyzed both as continuous and categorical variables. Results: Of the 17,382 children studied, 666 exhibited autistic traits. Exclusive breastfeeding for ≥2 months was notably associated with a decreased risk of developing autistic traits when it was assessed using continuous measures. Furthermore, children who were breastfed for 13 months or longer exhibited a lower risk of developing autistic traits, as compared to those who were breastfed for 6 months or less, when this was measured using categorical methods. Similarly, when it was assessed using continuous measures, children who were breastfed for at least 8 months also demonstrated a reduced risk of developing autistic traits. Linear relationships were discernible between exclusive breastfeeding duration, overall breastfeeding duration, and autistic traits. Conclusions: Exclusive breastfeeding for a period from 2 to 6 months, coupled with extended breastfeeding lasting for at least 8 months, demonstrated a beneficial effect in alleviating autistic traits among Chinese children. These findings contribute to refining and strengthening the existing recommendations concerning breastfeeding practices. Full article

Grape seed procyanidin extract (GSE) is widely used to promote cardiovascular health and has purported anti-inflammatory properties. Chronic inflammation in the lungs caused by environmental toxins such as tobacco smoking plays a pivotal role in lung cancer development. In a modified phase I lung cancer chemoprevention study conducted in heavy active and former smokers using leucoselect phytosome (LP), a standardized grape seed procyanidin extract complexed with soy phospholipids to enhance bioavailability, three months of LP treatment favorably modulated a variety of surrogate endpoint biomarkers, including markers of cell proliferation. In this correlative study, we further analyzed the effects of LP on cytochrome P450 3A4 (CYP3A4) activities by comparing the endogenous conversions of cortisol and cortisone to 6-beta-hydroxycortisol and 6-beta-hydroxycortisone, respectively, before and after LP treatment and the anti-inflammatory effects of LP in the lung microenvironment of these participants by comparing a profile of inflammatory cytokines and chemokines in matched pre- and post-treatment bronchoalveolar lavage (BAL) fluids. LP treatment did not significantly alter CYP3A4 activity, and three months of LP treatment significantly decreased tumor necrosis factor (TNF), C-C Motif Chemokine Ligand 3 (CCL3) and granzyme B in BAL fluids. Furthermore, post-LP-treatment BAL fluids significantly reduced migration/invasion of various human lung neoplastic cells in vitro. Our findings support the anti-inflammatory effects of GSE/LP in the lung microenvironment and its potential utility for reducing cancerizing forces, as well as driving forces for other common respiratory diseases such as chronic obstructive pulmonary disease and asthma, in the lungs of heavy former and active smokers. Full article

A major strategy to combat implant-associated infections is to develop implant coatings with intrinsic antibacterial activity. Since hydroxyapatite (HAp) coatings and antibiotic administration are commonly used in clinical settings, developing HAp-coated implants with localized antibiotic-releasing properties has attracted popularity. Considering the antibacterial metal species (Ag, Zn, Cu, etc.) in metal–organic frameworks and their drug delivery capacity, in this study, a gentamicin-loaded zeolitic imidazolate framework-8 nanolayer was deposited on a plasma-sprayed HAp coating (HAp/ZIF-8@Gent), which served as a Gent and Zn²⁺ reservoir. The investigation on the binding interaction between ZIF-8 and HAp indicated that the growth of ZIF-8 was through a Zn²⁺ seed layer on the HAp coating via an adsorption–replacement mechanism, instead of simple physical adsorption. The HAp/ZIF-8@Gent coating exhibited a sustained drug-release property, and the cumulative concentration of released Gent reached 239.8 ± 7.1 μg/mL on day 8. Compared to the HAp-Zn and HAp/ZIF-8 coatings, the HAp/ZIF-8@Gent coating exhibited significantly higher antibacterial activity against E. coli. This was ascribed to the combined antibacterial effects of Zn²⁺ and Gent. The cytocompatibility of the HAp/ZIF-8@Gent coating was confirmed via cell proliferation. Above all, the ZIF-8-modified HAp coating with localized delivery of Gent and Zn²⁺ possessed excellent antibacterial activity and acceptable cytocompatibility, showing potential in mitigating implant-associated infections. Full article

In the Suidae family, warthogs show significant survival adaptability and trait specificity. This study offers a comparative genomic analysis between the warthog and other Suidae species, including the Luchuan pig, Duroc pig, and Red River hog. By integrating the four genomes with sequences from the other four species, we identified 8868 single-copy orthologous genes. Based on 8868 orthologous protein sequences, phylogenetic assessments highlighted divergence timelines and unique evolutionary branches within suid species. Warthogs exist on different evolutionary branches compared to DRCs and LCs, with a divergence time preceding that of DRC and LC. Contraction and expansion analyses of warthog gene families have been conducted to elucidate the mechanisms of their evolutionary adaptations. Using GO, KEGG, and MGI databases, warthogs showed a preference for expansion in sensory genes and contraction in metabolic genes, underscoring phenotypic diversity and adaptive evolution direction. Associating genes with the QTLdb-pigSS11 database revealed links between gene families and immunity traits. The overlap of olfactory genes in immune-related QTL regions highlighted their importance in evolutionary adaptations. This work highlights the unique evolutionary strategies and adaptive mechanisms of warthogs, guiding future research into the distinct adaptability and disease resistance in pigs, particularly focusing on traits such as resistance to African Swine Fever Virus. Full article

Fat deposition is a significant economic trait in livestock animals. Adipose tissues (ATs) developed in subcutaneous and visceral depots are considered waste whereas those within muscle are highly valued. In river buffaloes, lipogenesis is highly active in subcutaneous (especially in the sternum subcutaneous) and visceral depots but not in muscle tissue. Revealing the features and functions of ATs in different depots is significant for the regulation of their development. Here, we characterize the cell size, composition, and function of six AT depots in river buffaloes. Our data support that the subcutaneous AT depots have a larger cell size than visceral AT depots, and the subcutaneous AT depots, especially the sternum subcutaneous AT, are mainly associated with the extracellular matrix whereas the visceral AT depots are mainly associated with immunity. We found that sternum subcutaneous AT is significantly different from ATs in other depots, due to the high unsaturated fatty acid content and the significant association with metabolic protection. The perirenal AT is more active in FA oxidation for energy supply. In addition, the expression of HOX paralogs supports the variable origins of ATs in different depots, indicating that the development of ATs in different depots is mediated by their progenitor cells. The present study enhances our understanding of the cellular and molecular features, metabolism, and origin of AT depots in buffaloes, which is significant for the regulation of fat deposition and provides new insights into the features of AT depots in multiple discrete locations. Full article

Microwave nondestructive testing (NDT) offers promising application prospects due to its advantages of non-contact inspection in detecting defects in non-metallic composites. However, the detection sensitivity of this technology is generally affected by the lift-off effect. To reduce this effect and highly concentrate electromagnetic fields on defects, a defect detection method using scanning instead of moving sensors in the microwave frequency range was proposed. Additionally, a novel sensor based on the programmable spoof surface plasmon polaritons (SSPPs) was designed for non-destructive detection in non-metallic composites. The unit structure of the sensor was made up of a metallic strip and a split ring resonator (SRR). A varactor diode was loaded between the inner and outer rings of the SRR, and by changing the capacitance of this diode using electronic scanning, the field concentration phenomenon of the SSPPs sensor can be moved along a specific direction for defect detection. By using this proposed method and sensor, the location of a defect can be analyzed without moving the sensor. The experimental results demonstrated that the proposed method and designed SSPPs sensor can be effectively applied in detecting defects in non-metallic materials. Full article

We recently demonstrated that the consumption of mixed tree nuts (MTNs) during caloric restriction decreased cardiovascular risk factors and increased satiety. Tryptophan (Trp) metabolism has been indicated as a factor in cardiovascular disease. Here, we investigated the effect of MTNs on Trp metabolism and the link to cardiovascular risk markers. Plasma and stool were collected from 95 overweight individuals who consumed either MTNs (or pretzels) daily as part of a hypocaloric weight loss diet for 12 weeks followed by an isocaloric weight maintenance program for an additional 12 weeks. Plasma and fecal samples were evaluated for Trp metabolites by LC–MS and for gut microbiota by 16S rRNA sequencing. Trp–kynurenine metabolism was reduced only in the MTNs group during weight loss (baseline vs. week 12). Changes in Trp–serotonin (week 24) and Trp–indole (week 12) metabolism from baseline were increased in the MTNs group compared to the pretzel group. Intergroup analysis between MTN and pretzel groups does not identify significant microbial changes as indicated by alpha diversity and beta diversity. Changes in the relative abundance of genus Paludicola during intervention are statistically different between the MTNs and pretzel group with p < 0.001 (q = 0.07). Our findings suggest that consumption of MTNs affects Trp host and microbial metabolism in overweight and obese subjects. Full article

Congenital disorders of glycosylation (CDG) are a heterogenous group of primarily autosomal recessive mendelian diseases caused by disruptions in the synthesis of lipid-linked oligosaccharides and their transfer to proteins. CDGs usually affect multiple organ systems and vary in presentation, even within families. There is currently no cure, and treatment is aimed at ameliorating symptoms and improving quality of life. Here, we describe a chemically induced mouse mutant, tvrm76, with early-onset photoreceptor degeneration. The recessive mutation was mapped to Chromosome 9 and associated with a missense mutation in the Dpagt1 gene encoding UDP-N-acetyl-D-glucosamine:dolichyl-phosphate N-acetyl-D-glucosaminephosphotransferase (EC 2.7.8.15). The mutation is predicted to cause a substitution of aspartic acid with glycine at residue 166 of DPAGT1. This represents the first viable animal model of a Dpagt1 mutation and a novel phenotype for a CDG. The increased expression of Ddit3, and elevated levels of HSPA5 (BiP) suggest the presence of early-onset endoplasmic reticulum (ER) stress. These changes were associated with the induction of photoreceptor apoptosis in tvrm76 retinas. Mutations in human DPAGT1 cause myasthenic syndrome-13 and severe forms of a congenital disorder of glycosylation Type Ij. In contrast, Dpagt1^tvrm76 homozygous mice present with congenital photoreceptor degeneration without overt muscle or muscular junction involvement. Our results suggest the possibility of DPAGT1 mutations in human patients that present primarily with retinitis pigmentosa, with little or no muscle disease. Variants in DPAGT1 should be considered when evaluating cases of non-syndromic retinal degeneration. Full article

Background: To explore the feasibility and effectiveness of multifaceted quality improvement intervention based on the clinical decision support system (CDSS) in VTE prophylaxis in hospitalized patients. Methods: A randomized, department-based clinical trial was conducted in the department of respiratory and critical care medicine, orthopedic, and general surgery wards. Patients aged ≥18 years, without VTE in admission, were allocated to the intervention group and received regular care combined with multifaceted quality improvement intervention based on CDSS during hospitalization. VTE prophylaxis rate and the occurrence of hospital-associated VTE events were analyzed as primary and secondary outcomes. Results: A total of 3644 eligible residents were enrolled in this trial. With the implementation of the multifaceted quality improvement intervention based on the CDSS, the VTE prophylaxis rate of the intervention group increased from 22.93% to 34.56% (p < 0.001), and the incidence of HA-VTE events increased from 0.49% to 1.00% (p = 0.366). In the nonintervention group, the VTE prophylaxis rate increased from 24.49% to 27.90% (p = 0.091), and the incidence of HA-VTE events increased from 0.47% to 2.02% (p = 0.001). Conclusions: Multifaceted quality improvement intervention based on the CDSS strategy is feasible and expected to facilitate implementation of the recommended VTE prophylaxis strategies and reduce the incidence of HA-VTE in hospital. However, it is necessary to conduct more multicenter clinical trials in the future to provide more reliable real-world evidence. Full article

Chemoresistance limits treatment outcomes in colorectal cancer (CRC) patients. A dimeric metabolite of indole-3-carbinol, 3,3′-diindolylmethane (DIM) is abundant in cruciferous vegetables and has shown anticancer efficacy. The role of DIM in regulating chemosensitivity in CRC remains unknown. In this study, we demonstrated that DIM treatment inhibits the malignant progression of CRC. RNA sequencing indicated that pyrimidine synthesis genes are attenuated by DIM treatment. Stable 1³C-labeled glucose tracing revealed that DIM inhibits de novo pyrimidine biosynthesis in CRC. DIM increases 5-FU cytotoxicity in CRC via regulation of the expression of pyrimidine metabolism-related genes. DIM synergizes with 5-FU to enhance its inhibitory effects on CRC both in vivo and in vitro. Our results suggest that DIM improves the therapeutic outcomes of FU-based chemotherapy in CRCs by inhibiting pyrimidine metabolism, identifying a new strategy for clinical therapy. Full article

Kombucha is an increasingly popular functional beverage that has gained attention for its unique combination of phytochemicals, metabolites, and microbes. Previous chemical and microbial composition analyses of kombucha have mainly focused on understanding their changes during fermentation. Very limited information is available regarding nutrient profiles of final kombucha products in the market. In this study, we compared the major chemicals (tea polyphenols, caffeine), antioxidant properties, microbial and metabolomic profiles of nine commercial kombucha products using shotgun metagenomics, internal transcribed spacer sequencing, untargeted metabolomics, and targeted chemical assays. All of the nine kombucha products showed similar acidity but great differences in chemicals, metabolites, microbes, and antioxidant activities. Most kombucha products are dominated by the probiotic Bacillus coagulans or bacteria capable of fermentation including Lactobacillus nagelii, Gluconacetobacter, Gluconobacter, and Komagataeibacter species. We found that all nine kombuchas also contained varying levels of enteric bacteria including Bacteroides thetaiotamicron, Escherischia coli, Enterococcus faecalis, Bacteroides fragilis, Enterobacter cloacae complex, and Akkermansia muciniphila. The fungal composition of kombucha products was characterized by predominance of fermenting yeast including Brettanomyces species and Cyberlindnera jadinii. Kombucha varied widely in chemical content assessed by global untargeted metabolomics, with metabolomic variation being significantly associated with metagenomic profiles. Variation in tea bases, bacteria/yeast starter cultures, and duration of fermentation may all contribute to the observed large differences in the microbial and chemical profiles of final kombucha products. Full article