Intake rates of methylmercury in the Belgian population: Evolution over 40 years.

Methylmercury (MeHg) is one of the most toxic compounds, it bioaccumulates and biomagnifies along the food chain and finally damages human's nervous system. Knowing that the main intake route for MeHg in humans is through fish consumption, intake rates were studied in various countries, but not in Belgium. Based on Hg and MeHg measurements in various fishes, mainly from North Sea catches, in combination with the national food consumption surveys, we could calculate daily Hg and MeHg intake rates for the Belgian population in 1975, 1997 and 2014-2021. These values are then compared with daily intake values reported by other countries and with the acceptable daily intake (ADI) values recommended by international organizations. Daily Hg and MeHg intake rates decreased strongly between 1975 and the 2 later periods: while average intake rates are all below the ADI norms, this is not the case for the 95th percentile rates because they exceed or are very close to the ADI values. Since daily MeHg intake rates correlate well with hair and blood concentrations, these were used as a good proxy of MeHg intoxication and were related to health effects observed in children, adolescents, adults and elderly persons living in Belgium via biomonitoring.

Comparative Analysis of Lennox-Gastaut Syndrome With Different Subtypes of Tonic Seizures: A Single-Center Retrospective Cohort Study.

BACKGROUND: Lennox-Gastaut syndrome (LGS) is one of the most severe childhood-onset epileptic encephalopathies, primarily characterized by tonic seizures. In clinical practice, we have identified various subtypes of tonic seizures in LGS. This study aimed to analyze the clinical characteristics, electrographic features, treatment responses, and prognosis across different subtypes of LGS. METHODS: This retrospective cohort study included 46 patients diagnosed with LGS at our center between January 2017 and January 2020. Patients were classified into four groups based on tonic seizure subtypes: Group A (tonic), Group B (spasm-tonic), Group C (myoclonic-tonic), and Group D (combination of spasm-tonic and myoclonic-tonic). Comprehensive clinical data were collected and analyzed. RESULTS: Of the 46 patients, 33 were male. The mean age of onset for Group B (12.38 ± 7.85 months) was significantly less than those of the other three groups (P = 0.02). No significant differences in etiology were found among the groups. Genetic analysis identified mutations in SCN8A, MCCC2, STXBP1, GABRB3, and CACNA1H. After a minimum follow-up of 24 months, the treatment outcomes were more favorable in Groups A and C, whereas psychomotor development was notably poorer in Groups B and D. CONCLUSIONS: The findings of this study suggest that LGS may present with distinct subtypes of tonic seizures, with spasm-tonic seizures presenting at an earlier age. Patients with LGS experiencing spasm-tonic seizures, with or without myoclonic-tonic seizures, exhibited poorer treatment responses and psychomotor development than those with other subtypes.

Transfusion burden and willingness to pay for temporary alleviation of anemia status in transfusion-dependent beta-thalassemia patients in China.

BACKGROUND: Transfusion-dependent ß-thalassemia (TDT) is one of the global public health concerns highlighted by the World Health Organization. Patients with TDT require regular blood transfusion to survive. However, the availability of blood resources is extremely limited. The purpose of this study was to investigate transfusion burden and willingness to pay (WTP) for temporary remission of anemia status among patients with TDT and to explore the associated factors. METHODS: Adult patients with TDT were recruited through cluster sampling across several high-incidence provinces in China. Consenting patients completed online questionnaires on demographic information, transfusion burden and WTP with real-time WeChat communication assistance from researchers. The guiding techniques of double-bounded dichotomous choices and open-ended questions in the contingent valuation method (CVM) were used to obtain participants' WTP for 1 unit of leukocyte-depleted red blood cells. WTP calculations were performed using maximum likelihood estimation, with further insights gained through subgroup analysis based on gender, family monthly income level and convenience of blood transfusion. RESULTS: The analysis included 149 TDT patients from five high-incidence provinces, with an average monthly income of $198.5. Patients received an average of 3.7 units per transfusion, 15.4 times annually, with an average WTP of $70.4 per unit (95% CI [62.0, 78.9]). Estimated WTP for temporary anemia alleviation per transfusion totaled $260.6, exceeding monthly income by 1.32 times. Higher WTP was observed among males, higher-income households, and those with at least junior education. Lower WTP was noted among patients with lower transfusion volumes and those needing to travel for transfusion or during hospitalization for blood transfusion. CONCLUSION: High WTP indicated a strong desire for temporary anemia relief. Most TDT patients faced significant economic and transfusion burden. The evident gap in meeting clinical needed underscores the urgent demand for innovative treatments to reduce transfusion dependency, potentially transforming TDT care and improving socioeconomic well-being and clinical outcomes. These findings supported evidence-based decision-making for TDT pharmacoeconomics and efficient healthcare resource allocation in China.

Enhancement of the flavor and functional characteristics of cod protein isolate using an enzyme-microbe system.

Cod protein isolate (CPI), a by-product of the cod processing industry, represents a novel source of high value-added products. However, off-flavors in cod protein such as bitterness and fishy odor reduce its acceptability to consumers. Here, CPI was first debittered using aminopeptidase from Streptomyces canus (ScAPase) and then deodorized through probiotic fermentation. This is the first reported demonstration of complete removal of the bitterness of CPI using ScAPase. Subsequently, Syn3 and Syn4, as aromatic CPI (ACPI), were prepared from debittered CPI (DCPI) via fermentation with Lactobacillus acidophilus and Bifidobacterium longum, respectively. These products, DCPI and ACPI, were characterized by the absence of bitterness and fishy odor, along with a strong aromatic scent and high overall acceptability. Additionally, these products exhibited improved physicochemical properties, including enhanced oil-holding capacity, emulsifying activity, and resistance to digestion, compared to untreated CPI. However, significant differences were observed in their radical scavenging activities. The highest scavenging activity was detected in Syn3 against DPPH˙ (63.5%) and ˙OH (79.2%), in DCPI against O2- (32.0%), and in post-digestion Syn4 against ABTS˙+ (95.2%). Furthermore, after digestion treatment, these products significantly promoted the proliferation of probiotics. Notably post-digestion Syn4 showed the most substantial proliferation effect on Lactobacillus reuteri, Lactobacillus rhamnosus, and Bifidobacterium breve compared to other post-digestion samples. These results indicate that the treated CPI has the potential for applications in health food products.

Sex differences in the metabolic activation of and platelet response to vicagrel in mice: Androgen as a key player.

As a biological variable, sex influences the metabolism of and/or response to certain drugs. Vicagrel is being developed as an investigational new drug in China; however, it is unknown whether sex could affect its metabolic activation and platelet responsiveness. This study aimed to determine whether such differences could exist, and to elucidate the mechanisms involved. Orchiectomized (ORX) or ovariectomized (OVX) mouse models were used to investigate the effects of androgen or estrogen on the metabolic activation of and platelet response to vicagrel. Plasma vicagrel active metabolite H4 concentrations, platelet inhibition of vicagrel, and protein levels of intestinal hydrolases Aadac and Ces2 were measured, respectively. Further, p38-MAPK signaling pathway was enriched, whose role was determined using SB202190. Results showed that female mice exhibited significantly elevated systemic exposure of H4 and enhanced platelet responses to vicagrel than males, and protein expression levels of Aadac and Ces2 differed by sex. OVX mice exhibited less changes than sham mice. ORX mice exhibited increases in protein levels of intestinal hydrolases, systemic exposure of H4, and platelet inhibition of vicagrel, but dihydrotestosterone (DHT) reversed these changes in ORX mice and suppressed these changes in OVX mice. Phosphorylated p38 levels were reduced in female or ORX mice but increased in ORX mice by DHT. SB202190 reversed DHT-induced changes observed in ORX mice. We concluded that sex differences exist in metabolic activation of and platelet response to vicagrel in mice through elevation of p38 phosphorylation by androgen, suggesting sex-based vicagrel dosage adjustments for patient care.

BpTCP19 targets BpWRKY53 to negatively regulate jasmonic acid- and dark-induced leaf senescence in Betula platyphylla.

TCP (TEOSINTE-LIKE1, CYCLOIDEA, and PROLIFERATING CELL FACTOR1) is a plant-specific transcription factor that has garnered significant attention due to its wide-ranging involvement in the regulation of plant growth or developmental processes. However, the molecular mechanisms through which TCP genes orchestrate leaf senescence have not been extensively elucidated. BpTCP19, a member of the PCF subfamily in Betula platyphylla, and has high homology to AtTCP19. BpTCP19 displayed pronounced downregulation in response to methyl jasmonate (MeJA) and dark treatment. Overexpressing BpTCP19 in Betula platyphylla led to a delay in leaf senescence, resulting in prolonged leaf greenness under both MeJA and dark conditions. Transcriptome analysis revealed that overexpression of BpTCP19 induced alterations in the expression levels of genes linked to cell proliferation, hormone signaling transduction, and leaf senescence, including the early responsive factor BpWRKY53. Furthermore, through Yeast one-hybrid assays and GUS analysis, BpTCP19 was shown to bind to the promoter region of BpWRKY53, suppressing its expression and thereby retarding leaf senescence. This study elucidates the physiological and molecular functions of BpTCP19 as a central transcriptional regulatory module in leaf senescence and provides a potential target gene for delaying leaf senescence by mitigating sensitivity to external aging signals such as Jasmonic acid (JA) and darkness.

Gut metagenomes of Asian octogenarians reveal metabolic potential expansion and distinct microbial species associated with aging phenotypes.

While rapid demographic changes in Asia are driving the incidence of chronic aging-related diseases, the limited availability of high-quality in vivo data hampers our ability to understand complex multi-factorial contributions, including gut microbial, to healthy aging. Leveraging a well-phenotyped cohort of community-living octogenarians in Singapore, we used deep shotgun-metagenomic sequencing for high-resolution taxonomic and functional characterization of their gut microbiomes (n = 234). Joint species-level analysis with other Asian cohorts identified distinct age-associated shifts characterized by reduction in microbial richness, and specific Alistipes and Bacteroides species enrichment (e.g., Alistipes shahii and Bacteroides xylanisolvens). Functional analysis confirmed these changes correspond to metabolic potential expansion in aging towards alternate pathways synthesizing and utilizing amino-acid precursors, vis-à-vis dominant microbial guilds producing butyrate in gut from pyruvate (e.g., Faecalibacterium prausnitzii, Roseburia inulinivorans). Extending these observations to key clinical markers helped identify >10 robust microbial associations to inflammation, cardiometabolic and liver health, including potential probiotic species (e.g., Parabacteroides goldsteinii) and pathobionts (e.g., Klebsiella pneumoniae), highlighting the microbiome's role as biomarkers and potential targets for promoting healthy aging.

Sleep patterns, genetic susceptibility, and venous thromboembolism: A prospective study of 384,758 UK Biobank participants.

BACKGROUND: Although healthy sleep patterns have been linked to a lower risk of cardiovascular disease in earlier research, it is unclear how beneficial they are for venous thromboembolism (VTE). AIM: This research aimed to examine the correlation between sleep patterns, genetic susceptibility, and VTE. METHODS: In the UK Biobank cohort, healthy sleep behaviors were defined as early chronotype, 7-8 hours of sleep each day, no snoring, infrequent insomnia, and infrequent daytime sleepiness. Each of the five criteria was given 1 point, creating a healthy sleep score ranging from 0 to 5. Cox proportional hazards regression models were utilized to examine the associations between genetic susceptibility, healthy sleep score and VTE. RESULTS: The UK Biobank study included 384,758 participants aged 56.6 ± 8.0 years. After a median of 11.9 years of follow-up, 8,885 (2.3%) participants were diagnosed with VTE. A healthy sleep score inversely affected VTE risk. For participants with a score of 5, the hazard ratio of VTE was 0.813 (95% confidence interval: 0.758-0.873, P<0.001) compared to those with a score ≤2. Early chronotype, sleeping 7-8 hours each day, infrequent insomnia, and infrequent daytime sleepiness were significantly associated with a 7.9%, 8.3%, 5.1%, and 20.7% lower risk of VTE, respectively. In addition, the correlation between sleep pattern and the incidence of VTE was consistent, regardless of genetic susceptibility (P for interaction = 0.366). CONCLUSIONS: Our secondary analysis of a large-scale prospectively gathered registry revealed that individuals with a healthy sleep pattern are significantly correlated with lower risk of developing VTE, irrespective of genetic susceptibility.

Ultrasensitive Detection of Trace Silver Ions Using MoS42--Intercalated LDH Nanosheets Enhanced SPR Sensor.

The widespread use of silver raises concerns about environmental and health risks, necessitating highly sensitive detection methods for trace silver ions (Ag+). Surface plasmon resonance (SPR) sensors offer benefits like label-free detection and rapid response, but their sensitivity for Ag+ detection is limited due to weak ion adsorption. Here, we developed an SPR sensor with MoS42--intercalated NiAl-layered double hydroxide (LDH) as the adsorption layer of Ag+ to enhance detection sensitivity. Our sensor achieves a sensitivity of 254.75 nm/µg/L and detects Ag+ at a low concentration of 2.8 pM, outperforming various existing sensors. It also shows excellent repeatability, long-term stability, and selectivity, proving effective in real-world environmental samples. This work advances high-performance SPR sensors for heavy metal ion detection.

Construction of a Bifunctional Nanoelectrode for Intracellular Natural Product Delivery and Monitoring Anticancer Efficiency in Single Cells.

Natural products play a significant role in new drug discovery and anticancer therapy, making the evaluation of their anticancer efficiency crucial for clinical application. However, delivering natural products to single cells and in situ monitoring of induced signaling molecule fluctuation to evaluate anticancer efficiency remain significant challenges. Hence, we proposed a universal and straightforward strategy to construct a bifunctional nanoelectrode that integrates drug loading and monitoring of signal molecule fluctuations at the single-cell level. Platinum (Pt) nanoparticles/reduced graphene oxide (rGO) composites were first electrochemically deposited on the carbon fiber nanoelectrode (CFNE@Pt/rGO) to serve as electrocatalytic materials for the monitoring of natural-product-induced reactive oxygen species (ROS) generation. The GO/natural product complex, formed by π-π stacking and hydrophobic interactions, was further electrochemically reduced on the surface of CFNE@Pt/rGO to enable the CFNE drug-loading function. Using this bifunctional functional nanoelectrode, a series of natural products (such as capsaicin, curcumin, and chrysin) were delivered into single cancer cells, and their anticancer efficiency was evaluated by measuring ROS generation. The results showed that intracellular ROS production induced by chrysin was 1.5-fold greater than that of curcumin and 2.1-fold greater than that of capsaicin. This work proposes an effective tool to evaluate the anticancer efficiency of various natural products. Additionally, this nanotool can be expanded to monitor the fluctuation of other biomolecules (such as RNS, GSH, NADH, etc.) by replacing Pt nanoparticles with other electrocatalytic materials, which is significant for comprehensively exploring the anticancer efficiency of new drugs and for the clinical treatment of various diseases.

Tauroursodeoxycholic acid targets HSP90 to promote protein homeostasis and extends healthy lifespan.

As the elderly population expands, the pursuit of therapeutics to reduce morbidity and extend lifespan has become increasingly crucial. As an FDA-approved drug for chronic cholestatic liver diseases, tauroursodeoxycholic acid (TUDCA), a natural bile acid, offers additional health benefits beyond liver protection. Here, we show that TUDCA extends the lifespan and healthspan of C. elegans. Importantly, oral supplementation of TUDCA improves fitness in old mice, including clinically relevant phenotypes, exercise capacity and cognitive function. Consistently, TUDCA treatment drives broad transcriptional changes correlated with anti-aging characteristics. Mechanistically, we discover that TUDCA targets the chaperone HSP90 to promote its protein refolding activity. This collaboration further alleviates aging-induced endoplasmic reticulum (ER) stress and facilitates protein homeostasis, thus offering resistance to aging. In summary, our findings uncover new molecular links between an endogenous metabolite and protein homeostasis, and propose a novel anti-aging strategy that could improve both lifespan and healthspan.

Comparing the obesogenic effect and regulatory mechanisms of long-term exposure to per/polyfluoroalkyl substances with different terminal groups in Caenorhabditis elegans.

Per/polyfluoroalkyl substances (PFASs) are ubiquitous, bioaccumulative, and recalcitrant contaminants, posing global exposure and health risks. The effects of chemical structures on toxicities and the mechanisms of their obesogenic effects were largely unclear. This study used the model organism Caenorhabditis elegans to assess the impact of long-term exposure to different PFASs (PFNA, PFOSA, PFBS, PFHxS, 6:2 FTS, 4:2 FTS, PFOA, and PFOS) on growth and lipid metabolism and discussed the obesogenic mechanisms of selected PFASs. The growth assays indicated longer carbon-fluorine (-CF) chains and total fluorine atoms increased developmental toxicity of PFASs, while at 8 -CF chain-length, PFNA (-COOH terminal), PFOS (-SO3 terminal), and PFOSA (-SO2NH2 terminal) exhibited differential growth inhibition. With the toxicity ranking of PFNA > PFOS > PFOSA, all PFASs significantly induced total lipid accumulation and perturbed the lipid composition in C. elegans. All three PFASs significantly induced lipogenesis gene expression and partially suppressed lipolysis genes. The results suggested that the disruption of lipid metabolism of PFOSA depends on sbp-1, while PFNA and PFOS depend on nhr-49. In conclusion, long-term exposure to PFNA, PFOSA, and PFOS triggers obesogenic effects in organisms by distinct molecular mechanisms.

The chromosome-scale assembly of the Notopterygium incisum genome provides insight into the structural diversity of coumarins.

Coumarins, derived from the phenylpropanoid pathway, represent one of the primary metabolites found in angiosperms. The alignment of the tetrahydropyran (THP) and tetrahydrofuran (THF) rings with the lactone structure results in the formation of at least four types of complex coumarins. However, the mechanisms underlying the structural diversity of coumarin remain poorly understood. Here, we report the chromosome-level genome assembly of Notopterygium incisum, spanning 1.64 Gb, with a contig N50 value of 22.7 Mb and 60,021 annotated protein-coding genes. Additionally, we identified the key enzymes responsible for shaping the structural diversity of coumarins, including two p-coumaroyl CoA 2'-hydroxylases crucial for simple coumarins basic skeleton architecture, two UbiA prenyltransferases responsible for angular or linear coumarins biosynthesis, and five CYP736 cyclases involved in THP and THF ring formation. Notably, two bifunctional enzymes capable of catalyzing both demethylsuberosin and osthenol were identified for the first time. Evolutionary analysis implies that tandem and ectopic duplications of the CYP736 subfamily, specifically arising in the Apiaceae, contributed to the structural diversity of coumarins in N. incisum. Conclusively, this study proposes a parallel evolution scenario for the complex coumarin biosynthetic pathway among different angiosperms and provides essential synthetic biology elements for the heterologous industrial production of coumarins.

Nomogram predicting the cardiovascular disease mortality for older patients with colorectal cancer: A real-world population-based study.

BACKGROUND: Cardio-oncology has received increasing attention especially among older patients with colorectal cancer (CRC). Cardiovascular disease (CVD)-specific mortality is the second-most frequent cause of death. The risk factors for CVD-specific mortality among older patients with CRC are still poorly understood. AIM: To identify the prognostic factors and construct a nomogram-based model to predict the CVD-specific mortality among older patients with CRC. METHODS: The data on older patients diagnosed with CRC were retrieved from The Surveillance, Epidemiology, and End Results database from 2004 to 2015. The prognostic factors and a nomogram-based model predicting the CVD-specific mortality were assessed using least absolute shrinkage and selection operator and Cox regression. RESULTS: A total of 141251 eligible patients with CRC were enrolled, of which 41459 patients died of CRC and 12651 patients died of CVD. The age at diagnosis, sex, marital status, year of diagnosis, surgery, and chemotherapy were independent prognostic factors associated with CVD-specific mortality among older patients with CRC. We used these variables to develop a model to predict CVD-specific mortality. The calibration curves for CVD-specific mortality probabilities showed that the model was in good agreement with actual observations. The C-index value of the model in the training cohort and testing cohort for predicting CVD-specific mortality was 0.728 and 0.734, respectively. CONCLUSION: The proposed nomogram-based model for CVD-specific mortality can be used for accurate prognostic prediction among older patients with CRC. This model is a potentially useful tool for clinicians to identify high-risk patients and develop personalized treatment plans.

Chemoproteomic profiling unveils binding and functional diversity of endogenous proteins that interact with endogenous triplex DNA.

Triplex DNA structures, formed when a third DNA strand wraps around the major groove of DNA, are key molecular regulators and genomic threats. However, the regulatory network governing triplex DNA dynamics remains poorly understood. Here we reveal the binding and functional repertoire of proteins that interact with triplex DNA through chemoproteomic profiling in living cells. We develop a chemical probe that exhibits exceptional specificity towards triplex DNA. By employing a co-binding-mediated proximity capture strategy, we enrich triplex DNA interactome for quantitative proteomics analysis. This enables the identification of a comprehensive list of proteins that interact with triplex DNA, characterized by diverse binding properties and regulatory mechanisms in their native chromatin context. As a demonstration, we validate DDX3X as an ATP-independent triplex DNA helicase to unwind substrates with a 5' overhang to prevent DNA damage. Overall, our study provides a valuable resource for exploring the biology and translational potential of triplex DNA.

Association Between Systolic Blood Pressure and in-Hospital Mortality Among Congestive Heart Failure Patients with Chronic Obstructive Pulmonary Disease in the Intensive Care Unit: A Retrospective Cohort Study.

Background: There has been a growing body of research focusing on patients with Congestive Heart Failure (CHF) and chronic obstructive pulmonary disease (COPD) admitted to the intensive care unit (ICU). However, the optimal blood pressure (BP) level for such patients remains insufficiently explored. This study aimed to investigate the associations between systolic blood pressure (SBP) and in-hospital mortality among ICU patients with both CHF and COPD. Methods: This retrospective cohort study enrolled 6309 patients from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. SBP was examined as both a continuous and categorical variable, with the primary outcome being in-hospital mortality. The investigation involved multivariable logistic regression, restricted cubic spline regression, and subgroup analysis to determine the relationship between SBP and mortality. Results: The cohort consisted of 6309 patients with concurrent CHF and COPD (3246 females and 3063 males), with an average age of 73.0 ± 12.5 years. The multivariate analysis revealed an inverse association between SBP and in-hospital mortality, both as a continuous variable (odds ratio = 0.99 [95% CI, 0.99~1]) and as a categorical variable (divided into quintiles). Restricted cubic spline analysis demonstrated an L-shaped relationship between SBP and mortality risk (P nonlinearity < 0.001), with an inflection point at 99.479 mmHg. Stratified analyses further supported the robustness of this correlation. Conclusion: The relationship between SBP and in-hospital mortality in patients with both CHF and COPD follows an L-shaped pattern, with an inflection point at approximately 99.479 mmHg.

Changes in Circulating CD44+CD62L- Treg Subsets and CD44-CD62L+ Treg Subsets Reflect the Clinical Status of Patients with Allergic Rhinitis.

INTRODUCTION: This study clarified the expression changes and clinical significance of CD44+CD62L- Treg and CD44-CD62L+ Treg subsets in the peripheral blood of patients with allergic rhinitis (AR). METHODS: The peripheral blood of 39 patients with AR and 42 healthy controls was collected. Clinical data, such as sex, age, IgE titer, allergen screening information and visual analogue scale (VAS) score, were recorded. Changes in serum IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ were detected using the cytometric bead array method. Flow cytometry was used to detect the proportions of Th1, Th2, Th17, TFH, and Th9 cells and the proportions of CD44+CD62L- Treg and CD44-CD62L+ Treg subsets. Correlation analysis was performed between the CD44+CD62L- Treg subsets and the CD44-CD62L+ Treg subsets with clinical indicators (VAS score, total IgE titer), cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ), and Th1/Th2/Th17/TFH/Th9 cell proportions. RESULTS: Compared to the control group, the proportion of total Treg cells and CD44+CD62L- Treg cells in the AR group decreased, and the proportion of CD44-CD62L+ Treg cells increased (p < 0.05). The proportions of CD44+CD62L- Treg cells significantly negatively correlated with Th2 cells (R = -0.5270, p < 0.05) and positively correlated with Treg cytokine IL-10 (R = 0.6447, p < 0.05). In addition, CD44+CD62L- Treg cells negatively correlated with the VAS score (R = -0.4956, p < 0.05), total IgE level (R = -0.4177, p < 0.05) and Th2 cytokine IL-6 level (R = -0.3034, p < 0.05) but positively correlated with the Th1 cytokine IL-2 (R = 0.4331, p < 0.05). In contrast, the proportion of CD44+CD62L- Treg cells significantly positively correlated with the Th2 cells (R = 0.6187, p < 0.05). Moreover, the proportion of CD44-CD62L+ Treg cells positively correlated with the VAS score (R = 0.4060, p < 0.05), total IgE level (R = 0.5224, p < 0.05) and Th2 cytokine IL-4 (R = 0.2647, p < 0.05) and IL-6 levels (R = 0.3824, p < 0.05) but negatively correlated with Th1 cytokine IL-2 (R = -0.3451, p < 0.05) and IL-10 (R = -0.3277, p < 0.05). CONCLUSION: A greater proportion of CD44+CD62L- Tregs correlated with better reversal of the Th1/Th2 imbalance and milder clinical symptoms in AR patients. The presence of more CD44-CD62L+ Tregs correlated with a weaker immunosuppressive effect on Th2 cells and more severe clinical symptoms in AR patients. These findings provide new perspectives for the treatment and disease monitoring of AR.

A model based on C-TIRADS combined with SWE for predicting Bethesda I thyroid nodules.

Objectives: This study aimed to explore the performance of a model based on Chinese Thyroid Imaging Reporting and Data Systems (C-TIRADS), clinical characteristics, and shear wave elastography (SWE) for the prediction of Bethesda I thyroid nodules before fine needle aspiration (FNA). Materials and methods: A total of 267 thyroid nodules from 267 patients were enrolled. Ultrasound and SWE were performed for all nodules before FNA. The nodules were scored according to the 2020 C-TIRADS, and the ultrasound and SWE characteristics of Bethesda I and non-I thyroid nodules were compared. The independent predictors were determined by univariate analysis and multivariate logistic regression analysis. A predictive model was established based on independent predictors, and the sensitivity, specificity, and area under the curve (AUC) of the independent predictors were compared with that of the model. Results: Our study found that the maximum diameter of nodules that ranged from 15 to 20 mm, the C-TIRADS category <4C, and E max <52.5 kPa were independent predictors for Bethesda I thyroid nodules. Based on multiple logistic regression, a predictive model was established: Logit (p) = -3.491 + 1.630 × maximum diameter + 1.719 × C-TIRADS category + 1.046 × E max (kPa). The AUC of the model was 0.769 (95% CI: 0.700-0.838), which was significantly higher than that of the independent predictors alone. Conclusion: We developed a predictive model for predicting Bethesda I thyroid nodules. It might be beneficial to the clinical optimization of FNA strategy in advance and to improve the accurate diagnostic rate of the first FNA, reducing repeated FNA.

PEG-SeNPs as therapeutic agents inhibiting apoptosis and inflammation of cells infected with H1N1 influenza A virus.

The rapid variation of influenza challenges vaccines and treatments, which makes an urgent task to develop the high-efficiency and low-toxicity new anti-influenza virus drugs. Selenium is one of the essential trace elements for the human body that possesses a good antiviral activity. In this study, we assessed anti-influenza A virus (H1N1) activity of polyethylene glycol (PEG)-modified gray selenium nanoparticles (PEG-SeNPs) on Madin-Darby Canine Kidney (MDCK) cells in vitro. CCK-8 assay showed that PEG-SeNPs had a protective effect on H1N1-infected MDCK cells. Moreover, PEG-SeNPs significantly reduced the mRNA level of H1N1. TUNEL-DAPI test showed that DNA damage reached a high level but effectively prevented after PEG-SeNPs treatment. Meanwhile, JC-1, Annexin V-FITC and cell cycle assay demonstrated the apoptosis induced by H1N1 was reduced greatly when treated with PEG-SeNPs. Furthermore, the downregulation of p-ATM, p-ATR and P53 protein, along with the upregualation of AKT protein indicated that PEG-SeNPs could inhibit H1N1-induced cell apoptosis through reactive oxygen species (ROS)-mediated related signaling pathways. Finally, Cytokine detection demonstrated PEG-SeNPs inhibited the production of pro-inflammatory factors after infection, including IL-1ß, IL-5, IL-6, and TNF-α. To sum up, PEG-SeNPs might become a new potential anti-H1N1 influenza virus drug due to its antiviral and anti-inflammatory activity.

Dietary vitamin K intake in relation to skeletal muscle mass and strength among adults: a cross-sectional study based on NHANES.

Background: Previous studies revealed that vitamin K might help maintain muscle homeostasis, but this association has received little attention. We aimed to explore the associations of vitamin K intake with skeletal muscle mass and strength. Methods: We included cross-sectional data from the U.S. National Health and Nutrition Examination Survey (NHANES, 2011-2018). Vitamin K intake was assessed via 24-h recall. Covariate-adjusted multiple linear regression and restricted cubic splines were used to evaluate the associations of dietary vitamin K intake with skeletal muscle mass and strength, measured by dual-energy X-ray absorptiometry and handgrip dynamometer, respectively. Results: Dietary vitamin K intake was positively associated with skeletal muscle mass in males (ß = 0.05747, p = 0.0204) but not in females. We also revealed a positive association between dietary vitamin K intake and handgrip strength within the range of 0-59.871 µg/d (P nonlinear = 0.049). However, beyond this threshold, increasing vitamin K intake did not cause additional handgrip strength improvements. Conclusion: We provided evidence for a positive relationship between dietary vitamin K intake and skeletal muscle mass in males. Moreover, our study revealed a nonlinear relationship between dietary vitamin K intake and handgrip strength, highlighting an optimal intake range.