MRS study on the correlation between frontal GABA+/Glx ratio and abnormal cognitive function in medication-naive patients with narcolepsy.

OBJECTIVE: To compare the GABA+/Glx (glutamate-glutamine) ratio in the prefrontal lobe under non-rapid eye movement sleep between patients with narcolepsy type 1 (NT1) and normal controls and explore the correlation between this difference and abnormal cognitive function, using synchronous electroencephalography-functional magnetic resonance spectroscopy (EEG-fMRS). METHODS: MRS measurements of GABA+ and Glx concentrations as well as synchronous EEG data were obtained from 26 medication-naive patients with NT1 and 29 sex- and age-matched healthy community volunteers. Cognition was appraised with the Beijing version of the Montreal Cognitive Assessment, and daytime sleepiness was measured using the Epworth Sleepiness Scale. All subjects recorded a 2-week sleep log as well as an overnight polysomnography within 1 week before MR scanning to understand their sleep habits and determine sleep stages. After PSG, they also underwent multiple sleep latency trials. Patient/control group differences in the individual measurements of GABA+ and Glx and the GABA+/Glx ratio and their relationship with cognition were assessed. RESULTS: The GABA+/Glx ratio and GABA + levels of patients with narcolepsy were higher than those of the control group (P＜0.0001 and P = 0.0008, respectively). However, there was no significant difference in Glx levels (P = 0.6360). The GABA+/Glx ratio negatively correlated with abnormal cognitive function (r = -0.6710, P = 0.0002). Moreover, GABA + levels were inversely proportional to rapid eye movement sleep latency (REML) in patients with narcolepsy (r = -0.5019, P = 0.0106). CONCLUSION: The GABA+/Glx ratio in the prefrontal lobe was higher in NT1 patients during N2 sleep than in normal controls, mainly caused by GABA + levels; this ratio was negatively related to abnormal cognitive function. In addition, GABA + levels were inversely proportional to REML.

Germline potential should not be overlooked for cancer variants identified in tumour-only somatic mutation testing.

DNA sequencing of tumour tissue has become the standard care for many solid cancers because of the option to detect somatic variants that have significant therapeutic, diagnostic and prognostic implications. Variants found within the tumour may be either somatic or germline in origin. Somatic cancer gene panels are developed to detect acquired (somatic) variants that are relevant for therapeutic or molecular characterisation of the tumour, expanding gene panels now include genes which may also inform patient management such as cancer predisposition syndromes (CPS) genes. Identifying germline cancer predisposition variants can alter cancer management, the risk of developing new primary cancers and risk for cancer in at-risk family members. This paper discusses the clinical, technical and ethical challenges related to identifying and reporting potential germline pathogenic variants that are detected on tumour sequencing. It also highlights the existence of the eviQ national guidelines for CPS with advice on germline confirmation of somatic findings to pathology laboratories in Australia.

Atrial Fibrillation and Clonal Hematopoiesis in TET2 and ASXL1.

Importance: Clonal hematopoiesis of indeterminate potential (CHIP) may contribute to the risk of atrial fibrillation (AF) through its association with inflammation and cardiac remodeling. Objective: To determine whether CHIP was associated with AF, inflammatory and cardiac biomarkers, and cardiac structural changes. Design, Setting, and Participants: This was a population-based, prospective cohort study in participants of the Atherosclerosis Risk in Communities (ARIC) study and UK Biobank (UKB) cohort. Samples were collected and echocardiography was performed from 2011 to 2013 in the ARIC cohort, and samples were collected from 2006 to 2010 in the UKB cohort. Included in this study were adults without hematologic malignancies, mitral valve stenosis, or previous mitral valve procedure from both the ARIC and UKB cohorts; additionally, participants without hypertrophic cardiomyopathy and congenital heart disease from the UKB cohort were also included. Data analysis was completed in 2023. Exposures: CHIP (variant allele frequency [VAF] ≥2%), common gene-specific CHIP subtypes (DNMT3A, TET2, ASXL1), large CHIP (VAF ≥10%), inflammatory and cardiac biomarkers (high-sensitivity C-reactive protein, interleukin 6 [IL-6], IL-18, high-sensitivity troponin T [hs-TnT] and hs-TnI, N-terminal pro-B-type natriuretic peptide), and echocardiographic indices. Main Outcome Measure: Incident AF. Results: A total of 199 982 adults were included in this study. In ARIC participants (4131 [2.1%]; mean [SD] age, 76 [5] years; 2449 female [59%]; 1682 male [41%]; 935 Black [23%] and 3196 White [77%]), 1019 had any CHIP (24.7%), and 478 had large CHIP (11.6%). In UKB participants (195 851 [97.9%]; mean [SD] age, 56 [8] years; 108 370 female [55%]; 87 481 male [45%]; 3154 Black [2%], 183 747 White [94%], and 7971 other race [4%]), 11 328 had any CHIP (5.8%), and 5189 had large CHIP (2.6%). ARIC participants were followed up for a median (IQR) period of 7.0 (5.3-7.7) years, and UKB participants were followed up for a median (IQR) period of 12.2 (11.3-13.0) years. Meta-analyzed hazard ratios for AF were 1.12 (95% CI, 1.01-1.25; P = .04) for participants with vs without large CHIP, 1.29 (95% CI, 1.05-1.59; P = .02) for those with vs without large TET2 CHIP (seen in 1340 of 197 209 [0.67%]), and 1.45 (95% CI, 1.02-2.07; P = .04) for those with vs without large ASXL1 CHIP (seen in 314 of 197 209 [0.16%]). Large TET2 CHIP was associated with higher IL-6 levels. Additionally, large ASXL1 was associated with higher hs-TnT level and increased left ventricular mass index. Conclusions and Relevance: Large TET2 and ASXL1, but not DNMT3A, CHIP was associated with higher IL-6 level, indices of cardiac remodeling, and increased risk for AF. Future research is needed to elaborate on the mechanisms driving the associations and to investigate potential interventions to reduce the risk.

Marinobacter qingdaonensis sp. nov., a moderately halotolerant bacterium isolated from intertidal sediment.

A Gram-stain-negative, aerobic, rod-shaped and halotolerant bacterium, designated as strain ASW11-75T, was isolated from intertidal sediments in Qingdao, PR China, and identified using a polyphasic taxonomic approach. Growth of strain ASW11-75T occurred at 10-45 °C (optimum, 37 °C), pH 6.5-9.0 (optimum, pH 8.0) and 0.5-18.0 % NaCl concentrations (optimum, 2.5 %). Phylogenetic analyses based on 16S rRNA gene sequences and 1179 single-copy orthologous clusters indicated that strain ASW11-75T is affiliated with the genus Marinobacter. Strain ASW11-75T showed highest 16S rRNA gene sequence similarity to 'Marinobacter arenosus' CAU 1620T (98.5 %). The digital DNA-DNA hybridization and average nucleotide identity values between strain ASW11-75T and its closely related strains (Marinobacter salarius R9SW1T, Marinobacter similis A3d10T, 'Marinobacter arenosus' CAU 1620T, Marinobacter sediminum R65T, Marinobacter salinus Hb8T, Marinobacter alexandrii LZ-8T and Marinobacter nauticus ATCC 49840T) were 19.8-24.5 % and 76.6-80.7 %, respectively. The predominant cellular fatty acids were C16 : 0, C18 : 1 ω9c and C16 : 0 N alcohol. The polar lipids were phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, one unidentified aminophospholipid and two unidentified lipids. The major isoprenoid quinone was ubiquinone-9. The genomic DNA G+C content was 62.2 mol%. Based on genomic and gene function analysis, strain ASW11-75T had lower protein isoelectric points with higher ratios of acidic residues to basic residues and possessed genes related to ion transport and organic osmoprotectant uptake, implying its potential tolerance to salt. The results of polyphasic characterization indicated strain ASW11-75T represents a novel Marinobacter species, for which the name Marinobacter qingdaonensis sp. nov. with the type strain ASW11-75T is proposed. The type strain is ASW11-75T (=KCTC 82497T=MCCC 1K05587T).

Formononetin protects against Aspergillus fumigatus Keratitis: Targeting inflammation and fungal load.

PURPOSE: To investigate the potential treatment of formononetin (FMN) on Aspergillus fumigatus (A. fumigatus) keratitis with anti-inflammatory and antifungal activity. METHODS: The effects of FMN on mice with A. fumigatus keratitis were evaluated through keratitis clinical scores, hematoxylin-eosin (HE) staining, and plate counts. The expression of pro-inflammatory factors was measured using RT-PCR, ELISA, or Western blot. The distribution of macrophages and neutrophils was explored by immunofluorescence staining. The antifungal properties of FMN were assessed through minimum inhibitory concentration (MIC), propidium iodide (PI) staining, fungal spore adhesion, and biofilm formation assay. RESULTS: In A. fumigatus keratitis mice, FMN decreased the keratitis clinical scores, macrophages and neutrophils migration, and the expression of TNF-α, IL-6, and IL-1ß. In A. fumigatus-stimulated human corneal epithelial cells (HCECs), FMN reduced the expression of IL-6, TNF-α, IL-1ß, and NLRP3. FMN also decreased the expression of thymic stromal lymphopoietin (TSLP) and thymic stromal lymphopoietin receptor (TSLPR). Moreover, FMN reduced the levels of reactive oxygen species (ROS) induced by A. fumigatus in HCECs. Furthermore, FMN inhibited A. fumigatus growth, prevented spore adhesion and disrupted fungal biofilm formation in vitro. In vivo, FMN treatment reduced the fungal load in mice cornea at 3 days post infection (p.i.). CONCLUSION: FMN demonstrated anti-inflammatory and antifungal properties, and exhibited a protective effect on mouse A. fumigatus keratitis.

Grape seed proanthocyanidin extract promotes skeletal muscle fiber type transformation through modulation of cecal microbiota and enhanced butyric acid production.

The conversion of fast-twitch fibers into slow-twitch fibers within skeletal muscle plays a crucial role in improving physical stamina and safeguarding against metabolic disorders in individuals. Grape seed proanthocyanidin extract (GSPE) possesses numerous pharmacological and health advantages, effectively inhibiting the onset of chronic illnesses. However, there is a lack of research on the specific mechanisms by which GSPE influences muscle physiology and gut microbiota. This study aims to investigate the role of gut microbiota and their metabolites in GSPE regulation of skeletal muscle fiber type conversion. In this experiment, 54 male BALB/c mice were randomly divided into three groups: basal diet, basal diet supplemented with GSPE, and basal diet supplemented with GSPE and antibiotics. During the feeding period, glucose tolerance and forced swimming tests were performed. After euthanasia, samples of muscle and feces were collected for analysis. The results showed that GSPE increased the muscle mass and anti-fatigue capacity of the mice, as well as the expression of slow-twitch fibers. However, the beneficial effects of GSPE on skeletal muscle fibers disappeared after adding antibiotics to eliminate intestinal microorganisms, suggesting that GSPE may play a role by regulating intestinal microbial structure. In addition, GSPE increased the relative abundance of Blautia, Muribaculaceae, and Enterorhabdus, as well as butyrate production. Importantly, these gut microbes exhibited a significant positive correlation with the expression of slow-twitch muscle fibers. In conclusion, supplementation with GSPE can increase the levels of slow-twitch fibers by modulating the gut microbiota, consequently prolonging the duration of exercise before exhaustion. PRACTICAL APPLICATION: This research suggests that grape seed proanthocyanidin extract (GSPE) has potential applications in improving physical stamina and preventing metabolic disorders. By influencing the gut microbiota and increasing butyric acid production, GSPE contributes to the conversion of fast-twitch muscle fibers into slow-twitch fibers, thereby enhancing anti-fatigue capacity and exercise endurance. While further studies are needed, incorporating GSPE into dietary supplements or functional foods could support individuals seeking to optimize their exercise performance and overall metabolic health.

Subtherapeutic Kitasamycin Promoted Fat Accumulation in the Longissimus Dorsi Muscle in Growing-Finishing Pigs.

Kitasamycin (KM), a broad-spectrum macrolide antibiotic, has implications for growth performance and residue in animals and humans. This study aimed to explore the effects of different KM doses on intramuscular fat accumulation, cecal microflora, and short-chain fatty acids (SCFAs) using a growing-finishing pig model. Forty-two pigs were divided into three groups: control, subtherapeutic KM (50 mg/kg, KM50), and therapeutic KM (200 mg/kg, KM200) diets over 8 weeks. KM50 led to increased back fat thickness, fat content in the longissimus dorsi muscle (LM), and elevated plasma total cholesterol (TC) levels (p < 0.05), supported by upregulated lipid synthesis gene expression (Acc1, Fas, Scd1) (p < 0.05) in the LM. KM50 altered cecal microflora, reducing Lactobacillus spp. and Bifidobacterium spp. abundance, while increasing SCFA concentrations (acetic acid, propionic acid, total SCFAs) (p < 0.05). KM200 had minimal effects on intestinal weight and density, with increased apparent digestibility of nutrients. These findings highlight the dose-dependent impact of KM on intramuscular fat deposition. Subtherapeutic KM induced ectopic fat deposition, emphasizing potential risks in disease treatment for humans and animals.

Current research status and development prospects of embolic microspheres containing biological macromolecules and others.

Transcatheter arterial embolization (TACE) has been used in the treatment of malignant tumors, sudden hemorrhage, uterine fibroids, and other diseases, and with advances in imaging techniques and devices, materials science, and drug release technology, more and more embolic agents that are drug-carrying, self-imaging, or have multiple functions are being developed. Microspheres provide safer and more effective therapeutic results as embolic agents, with their unique spherical appearance and good embolic properties. Embolic microspheres are the key to arterial embolization, blocking blood flow and nutrient supply to the tumor target. This review summarizes some of the currently published embolic microspheres, classifies embolic microspheres according to matrix, and summarizes the characteristics of the microsphere materials, the current status of research, directions, and the value of existing and potential applications. It provides a direction to promote the development of embolic microspheres towards multifunctionalization, and provides a reference to promote the research and application of embolic microspheres in the treatment of tumors.

Nanodrugs based on co-delivery strategies to combat cisplatin resistance.

Cisplatin (CDDP), as a broad-spectrum anticancer drug, is able to bind to DNA and inhibit cell division. Despite the widespread use of cisplatin since its discovery, cisplatin resistance developed during prolonged chemotherapy, similar to other small molecule chemotherapeutic agents, severely limits its clinical application. Cisplatin resistance in cancer cells is mainly caused by three reasons: DNA repair, decreased cisplatin uptake/increased efflux, and cisplatin inactivation. In earlier combination therapies, the emergence of multidrug resistance (MDR) in cancer cells prevented the achievement of the desired therapeutic effect even with the accurate combination of two chemotherapeutic drugs. Therefore, combination therapy using nanocarriers for co-delivery of drugs is considered to be ideal for alleviating cisplatin resistance and reducing cisplatin-related toxicity in cancer cells. This article provides an overview of the design of cisplatin nano-drugs used to combat cancer cell resistance, elucidates the mechanisms of action of cisplatin and the pathways through which cancer cells develop resistance, and finally discusses the design of drugs and related carriers that can synergistically reduce cancer resistance when combined with cisplatin.

Protective effect of Broussonetia papyrifera leaf polysaccharides on intestinal integrity in a rat model of diet-induced oxidative stress.

This study aimed to investigate the effect of Broussonetia papyrifera polysaccharides (BPP) on the jejunal intestinal integrity of rats ingesting oxidized fish oil (OFO) induced oxidative stress. Polysaccharides (Mw 16,956 Da) containing carboxyl groups were extracted from Broussonetia papyrifera leaves. In vitro antioxidant assays showed that this polysaccharide possessed antioxidant capabilities. Thirty-two male weaned rats were allocated into two groups orally infused BPP solution and PBS for 26 days, respectively. From day 9 to day 26, half of the rats in each group were fed food containing OFO, where the lipid peroxidation can induce intestinal oxidative stress. OFO administration resulted in diarrhea, decreased growth performance (p < 0.01), impaired jejunal morphology (p < 0.05) and antioxidant capacity (p < 0.01), increased the levels of ROS and its related products, IL-1ß and IL-17 (p < 0.01) of jejunum, as well as down-regulated Bcl-2/Bax (p < 0.01) and Nrf2 signaling (p < 0.01) of jejunum in rats. BPP gavage effectively alleviated the negative effects of OFO on growth performance, morphology, enterocyte apoptosis, antioxidant capacity and inflammation of jejunum (p < 0.05) in rats. In the oxidative stress model cell assay, the use of receptor inhibitors inhibited the enhancement of antioxidant capacity by BPP. These results suggested that BPP protected intestinal morphology, thus improving growth performance and reducing diarrhea in rats ingesting OFO. This protective effect may be attributed to scavenging free radicals and activating the Nrf2 pathway, which enhances antioxidant capacity, consequently reducing inflammation and mitigating intestinal cell death.

Leucine alleviates cytokine storm syndrome by regulating macrophage polarization via the mTORC1/LXRα signaling pathway.

Cytokine storms are associated with severe pathological damage and death in some diseases. Excessive activation of M1 macrophages and the subsequent secretion of pro-inflammatory cytokines are a major cause of cytokine storms. Therefore, promoting the polarization of M2 macrophages to restore immune balance is a promising therapeutic strategy for treating cytokine storm syndrome (CSS). This study was aimed at investigating the potential protective effects of leucine on lipopolysaccharide (LPS)-induced CSS in mice and exploring the underlying mechanisms. CSS was induced by LPS administration in mice, which were concurrently administered leucine orally. In vitro, bone marrow derived macrophages (BMDMs) were polarized to M1 and M2 phenotypes with LPS and interleukin-4 (IL-4), respectively, and treated with leucine. Leucine decreased mortality in mice treated with lethal doses of LPS. Specifically, leucine decreased M1 polarization and promoted M2 polarization, thus diminishing pro-inflammatory cytokine levels and ameliorating CSS in mice. Further studies revealed that leucine-induced macrophage polarization through the mechanistic target of rapamycin complex 1 (mTORC1)/liver X receptor α (LXRα) pathway, which synergistically enhanced the expression of the IL-4-induced M2 marker Arg1 and subsequent M2 polarization. In summary, this study revealed that leucine ameliorates CSS in LPS mice by promoting M2 polarization through the mTORC1/LXRα/Arg1 signaling pathway. Our findings indicate that a fundamental link between metabolism and immunity contributes to the resolution of inflammation and the repair of damaged tissues.

The effect of Tai Chi lower extremity exercise on the balance control of older adults in assistant living communities.

BACKGROUND: Although Tai Chi (TC) is an evidence-based fall prevention training for older adults, its effective movements remain unclear, which may limit the practice of TC. The purpose of this study was to compare the effectiveness of TC lower extremity exercise (TC LEE), the 8-form Tai Chi (8-form TC), and a stretching control intervention for improving balance and functional mobility among older adults. METHODS: This was a randomized controlled trial. A total of 102 participants (79 ± 6 years old) were recruited from assisted living facilities. All participants were randomly assigned to the TC LEE (n = 40), 8-form TC (n = 31), and stretching (n = 31) groups in which they received the respective interventions for 16 weeks. The Berg Balance Scale (BBS), Timed Up and Go (TUG) test, and center of pressure (COP) measurements during quiet stance were collected prior to and following the 16-week interventions. Comparisons on all measurements were conducted among all groups. RESULTS: Significant improvements were found in BBS (P = 0.002), TUG test (P = 0.001), root mean square amplitude of COP displacement in the anterior-posterior (P = 0.001) and medial-lateral (P = 0.001) directions, and average COP speed in the anterior-posterior (P = 0.001) and medial-lateral (P = 0.001) directions after training in the TC intervention groups compared with the stretching group. The upper limit of the 95% confidence interval (CI) of differences in change scores on the BBS (-0.8 - 1.3 points) between the TC LEE group and the 8-form TC group was within equivalence margins (1.8 points), while the upper limit of the 95% CI of differences in change scores on the TUG test (0.1 - 2.1 s) exceeded the equivalence margin (0.7 s) with the TC LEE group having the larger change scores. CONCLUSION: TC LEE can improve balance and functional mobility in older adults, and may have greater effect than the 8-form TC on improving functional mobility as measured by the TUG test. TRIAL REGISTRATION: ChiCTR2300070600 retrospectively registered.

Metabolomic Association and Risk Prediction With Heart Failure in Older Adults.

BACKGROUND: Older adults have markedly increased risks of heart failure (HF), specifically HF with preserved ejection fraction (HFpEF). Identifying novel biomarkers can help in understanding HF pathogenesis and improve at-risk population identification. This study aimed to identify metabolites associated with incident HF, HFpEF, and HF with reduced ejection fraction and examine risk prediction in older adults. METHODS: Untargeted metabolomic profiling was performed in Black and White adults from the ARIC study (Atherosclerosis Risk in Communities) visit 5 (n=3719; mean age, 75 years). We applied Cox regressions to identify metabolites associated with incident HF and its subtypes. The metabolite risk score (MRS) was constructed and examined for associations with HF, echocardiographic measures, and HF risk prediction. Independent samples from visit 3 (n=1929; mean age, 58 years) were used for replication. RESULTS: Sixty metabolites (hazard ratios range, 0.79-1.49; false discovery rate, <0.05) were associated with incident HF after adjusting for clinical risk factors, eGFR, and NT-proBNP (N-terminal pro-B-type natriuretic peptide). Mannonate, a hydroxy acid, was replicated (hazard ratio, 1.36 [95% CI, 1.19-1.56]) with full adjustments. MRS was associated with an 80% increased risk of HF per SD increment, and the highest MRS quartile had 8.7× the risk of developing HFpEF than the lowest quartile. High MRS was also associated with unfavorable values of cardiac structure and function. Adding MRS over clinical risk factors and NT-proBNP improved 5-year HF risk prediction C statistics from 0.817 to 0.850 (∆C, 0.033 [95% CI, 0.017-0.047]). The association between MRS and incident HF was replicated after accounting for clinical risk factors (P<0.05). CONCLUSIONS: Novel metabolites associated with HF risk were identified, elucidating disease pathways, specifically HFpEF. An MRS was associated with HF risk and improved 5-year risk prediction in older adults, which may assist at at-risk population identification.

Gut Microbiota and Blood Metabolites Related to Fiber Intake and Type 2 Diabetes.

BACKGROUND: Consistent evidence suggests diabetes-protective effects of dietary fiber intake. However, the underlying mechanisms, particularly the role of gut microbiota and host circulating metabolites, are not fully understood. We aimed to investigate gut microbiota and circulating metabolites associated with dietary fiber intake and their relationships with type 2 diabetes (T2D). METHODS: This study included up to 11 394 participants from the HCHS/SOL (Hispanic Community Health Study/Study of Latinos). Diet was assessed with two 24-hour dietary recalls at baseline. We examined associations of dietary fiber intake with gut microbiome measured by shotgun metagenomics (350 species/85 genera and 1958 enzymes; n=2992 at visit 2), serum metabolome measured by untargeted metabolomics (624 metabolites; n=6198 at baseline), and associations between fiber-related gut bacteria and metabolites (n=804 at visit 2). We examined prospective associations of serum microbial-associated metabolites (n=3579 at baseline) with incident T2D over 6 years. RESULTS: We identified multiple bacterial genera, species, and related enzymes associated with fiber intake. Several bacteria (eg, Butyrivibrio, Faecalibacterium) and enzymes involved in fiber degradation (eg, xylanase EC3.2.1.156) were positively associated with fiber intake, inversely associated with prevalent T2D, and favorably associated with T2D-related metabolic traits. We identified 159 metabolites associated with fiber intake, 47 of which were associated with incident T2D. We identified 18 of these 47 metabolites associated with the identified fiber-related bacteria, including several microbial metabolites (eg, indolepropionate and 3-phenylpropionate) inversely associated with the risk of T2D. Both Butyrivibrio and Faecalibacterium were associated with these favorable metabolites. The associations of fiber-related bacteria, especially Faecalibacterium and Butyrivibrio, with T2D were attenuated after further adjustment for these microbial metabolites. CONCLUSIONS: Among United States Hispanics/Latinos, dietary fiber intake was associated with favorable profiles of gut microbiota and circulating metabolites for T2D. These findings advance our understanding of the role of gut microbiota and microbial metabolites in the relationship between diet and T2D.

Synthesis on NIR-II Multifunctional Imaging and Photothermal Therapy of a Novel Water-Soluble Molecule.

The synthesis of water-soluble symmetric molecules with donor-acceptor-donor (D-A-D) structure is reported. The compound is connected by π bridge with 2-bromofluorene external polyethylene glycol 2000 as the shielding unit, and donor component and pyrrolopyrrole (DPP) as the acceptor unit. The D-A-D double donor fluorescent molecule P2-DPP is obtained by coupling reaction. The absorption peak and emission peak of the fluorescent molecule P2-DPP are 600 and 1020 nm, respectively. It has potential excellent imaging characteristics. It does not need to use nanoparticles formed by the DSPE-MPEG amphiphilic block to form micelles. The quantum yield reaches 0.6% and the penetration depth can reach 10 mm. The chemical is capable of achieving liver and renal metabolism. It has a good application prospect in the photothermal therapy of mouse tumors and realizes the integration of biological diagnosis and treatment.

Serum Metabolomic Markers of Protein-Rich Foods and Incident CKD: Results From the Atherosclerosis Risk in Communities Study.

Rationale & Objective: While urine excretion of nitrogen estimates the total protein intake, biomarkers of specific dietary protein sources have been sparsely studied. Using untargeted metabolomics, this study aimed to identify serum metabolomic markers of 6 protein-rich foods and to examine whether dietary protein-related metabolites are associated with incident chronic kidney disease (CKD). Study Design: Prospective cohort study. Setting & Participants: A total of 3,726 participants from the Atherosclerosis Risk in Communities study without CKD at baseline. Exposures: Dietary intake of 6 protein-rich foods (fish, nuts, legumes, red and processed meat, eggs, and poultry), serum metabolites. Outcomes: Incident CKD (estimated glomerular filtration rate < 60 mL/min/1.73 m2 with ≥25% estimated glomerular filtration rate decline relative to visit 1, hospitalization or death related to CKD, or end-stage kidney disease). Analytical Approach: Multivariable linear regression models estimated cross-sectional associations between protein-rich foods and serum metabolites. C statistics assessed the ability of the metabolites to improve the discrimination of highest versus lower 3 quartiles of intake of protein-rich foods beyond covariates (demographics, clinical factors, health behaviors, and the intake of nonprotein food groups). Cox regression models identified prospective associations between protein-related metabolites and incident CKD. Results: Thirty significant associations were identified between protein-rich foods and serum metabolites (fish, n = 8; nuts, n = 5; legumes, n = 0; red and processed meat, n = 5; eggs, n = 3; and poultry, n = 9). Metabolites collectively and significantly improved the discrimination of high intake of protein-rich foods compared with covariates alone (difference in C statistics = 0.033, 0.051, 0.003, 0.024, and 0.025 for fish, nuts, red and processed meat, eggs, and poultry-related metabolites, respectively; P < 1.00 × 10-16 for all). Dietary intake of fish was positively associated with 1-docosahexaenoylglycerophosphocholine (22:6n3), which was inversely associated with incident CKD (HR, 0.82; 95% CI, 0.75-0.89; P = 7.81 × 10-6). Limitations: Residual confounding and sample-storage duration. Conclusions: We identified candidate biomarkers of fish, nuts, red and processed meat, eggs, and poultry. A fish-related metabolite, 1-docosahexaenoylglycerophosphocholine (22:6n3), was associated with a lower risk of CKD.

In this study, we aimed to identify associations between protein-rich foods (fish, nuts, legumes, red and processed meat, eggs, and poultry) and serum metabolites, which are small biological molecules involved in metabolism. Metabolites significantly associated with a protein-rich food individually and collectively improved the discrimination of the respective protein-rich food, suggesting that these metabolites should be prioritized in future diet biomarker research. We also studied associations between significant diet-related metabolites and incident kidney disease. One fish-related metabolite was associated with a lower kidney disease risk. This finding supports the recent nutritional guidelines recommending a Mediterranean diet, which includes fish as the main dietary protein source.

Continuous monitoring of endotracheal tube position with near infrared light.

Significance: Endotracheal intubation is a common approach for airway management in critically ill patients. However, the position of the endotracheal tube (ETT) may be altered during the procedure due to head movements. Accidental displacement or dislodge of the ETT may reduce the airflow, leading to moderate to severe complications, and in some cases even fatality. Therefore, timely detection of changes in ETT position in the trachea is critical to ensure immediate and intermediate interventions to maintain the ETT in the proper position. Currently, there are no widely utilized tools for real-time monitoring of ETT positions. Aim: The goal of this study is to develop a cost-effective and easy-to-use near-infrared (NIR) device, named Opt-ETT, capable of continuously monitoring the ETT position in the trachea of a patient. Approach: A side-firing fiber is attached to the side of the ETT to illuminate the trachea tissue with NIR light, and a detector board containing five phototransistors is affixed to the chest skin to measure the intensity of diffusely transmitted light. Displacement of the ETT is estimated using second-order polynomial fitting to the ratios of the phototransistor readings. Monte Carlo simulations, ex vivo experiment on porcine tissue, and in vivo experiments using a swine model have been conducted to assess the feasibility of the device. Results: The design of the Opt-ETT device has been verified by the Monte Carlo simulations and ex vivo experiment. The estimation of displacement from in vivo experiments using the Opt-ETT exhibited a high degree of agreement with that measured by a reference sensor, with a discrepancy between -1.0 to +1.5 mm within a displacement range from -15 to +15 mm. Conclusions: The Opt-ETT device provides a potentially cost-effective solution for real-time and continuous monitoring of ETT position in patient during an intubation procedure.

Resveratrol ameliorates DSS-induced ulcerative colitis by acting on mouse gut microbiota.

OBJECTIVE AND DESIGN: Ulcerative colitis (UC) is a multi-faceted, recurrent immune disorder caused by dextran sulfate sodium (DSS). The intestinal microbiota has multiple functions in the host, so UC requires long-term potent medication. The effect of resveratrol (RSV) has seldom been reported, and this study researched that. Herein, the effect of RSV and Grape seed oil that anti-inflammatory ability in experimental mice was explored, also why RSV altered Gut Microbiota has been researched. MATERIALS AND METHODS: In this experiment, the effects of experimental drugs on colon length in mice with DSS-induced colitis were compared. H&E Staining was performed on serial sections of colon tissues and histological scores were determined for all groups. The expression of cyclooxygenase-2 (COX-2) and tumor necrosis factor-α (TNF-α) in the colon tissue of mice was detected by immunohistochemical staining. In the end, the α-diversity index, sobs index, and rarefaction curve of the cecal and colon microbiota of different groups of mice were measured. Bray-Curtis-based Venn diagram of PCoA (principal coordinate analysis) and OTUs distribution in mouse gut microbiota were obtained. RESULTS: The results showed that the use of 40 mg/kg RSV (high dose) significantly reduced the severity of UC. The use of 10 mg/kg RSV (low dose) significantly reduced the effect of shortened colon length in DSS mice. Compared with the DSS-treated group, the levels of COX-2 and TNF-α in the colon tissues of RSV + DSS-treated mice were significantly decreased. According to this experiment, 19 mouse gut microbiota species had a relative abundance greater than 0.1%, with Beerella, Bacteroides, Helicobacter, Oscillator, and cecum pylori being more abundant in the colon than in the colon. A higher relative abundance of Lachnospira NK4A136 was observed in DSS and RSV groups compared with the control group, whereas the opposite was observed for Alloprevotella. This proves that resveratrol increases the uniformity and diversity of gut microbes to a certain extent, and has a protective effect on the gut.

Identification of a novel Scn3b mutation in a Chinese Brugada syndrome pedigree: implications for Nav1.5 electrophysiological properties and intracellular distribution of Nav1.5 and Navß3.

Background: The Scn3b gene encodes for Navß3, a pivotal regulatory subunit of the fast sodium channel in cardiomyocytes. However, its mutation status in the Chinese population suffering from Brugada Syndrome (BrS) has not been characterized, and the contributory pathophysiological mechanisms to disease pathology remain undefined. Methods and Results: A Scn3b (c.260C>T, p.P87l) mutation was identified in a patient with BrS of Chinese descent. Functional analyses demonstrated that sodium channel activation for the wild type, mutant samples, and co-expression of both commenced at -55 mv and peaked at -25 mv. The mutant group exhibited a notable reduction, approximately 60%, in peak sodium channel activation current (INa) at -25 mv. The parameters for half-maximal activation voltages (V1/2) and slope factors (k) showed no significant differences when comparing wild type, mutant, and combined expression groups (P = 0.98 and P = 0.65, respectively). Additionally, no significant disparities were evident in terms of the steady-state sodium channel inactivation parameters V1/2 and k (with P-values of 0.85 and 0.25, respectively), nor were there significant differences in the activation time constant τ (P = 0.59) and late sodium current density (P = 0.23) across the wild-type, mutant, and co-expressed groups. Confocal imaging and Western blot analysis demonstrated decreased plasma membrane localization of SCN3B and SCN5A in the P87l group. Computational simulations of cardiac action potentials suggested that SCN3B P87l can alter the morphology of the action potentials within the endocardium and epicardium while reducing the peak of depolarization. Conclusions: The pathogenic impact of the Scn3b P87l mutation predominantly originates from a reduction in peak INa activation current coupled with decreased cell surface expression of Nav1.5 and Navß3. These alterations may influence cardiac action potential configurations and contribute to the risk of ventricular arrhythmias in individuals with BrS.

East Asia Superciliary Arch Augmentation With Silicone Implant.

OBJECTIVE: A flat superciliary arch is relatively common in East Asian women. Superciliary arch augmentation aims to increase the facial three-dimensionality of the upper face. However, there are few reports in the literature specifically introducing the surgery. In this study, the authors present the clinical outcomes after a series of superciliary arch augmentation with silicone implants. METHODS: From May 2020 to December 2022, 54 patients underwent superciliary arch augmentation with silicone implants. Silicone implants generally have a length of 50 to 60 mm, a width of 13 to 14 mm, and an arc of 170 degrees. The thickness was 2 to 7 mm. The implant was placed subperiosteal at the lower edges of the eyebrows through a 7 mm incision below the brow tail. All patients evaluated the outcome according to the Global Esthetic Improvement Scale. Four plastic surgeons evaluated postsurgery results with a 5-point Likert Scale (5 = excellent, 4 = good, 3 = fair, 2 = no change, and 1 = worse). RESULTS: Fifty-four patients were successfully enrolled. The mean follow-up period was 12.02 ± 3.38 months. The mean thickness was 4.55 ± 0.67 mm for the thickest part of the implant. The minor complication rate was 44.44%. They all subsided within 1 month without treatment. Patients' outcome ratings were 4.45 ± 0.55 (3 mo), 4.51 ± 0.48 (6 mo), and 4.51 ± 0.45 (1 y). The surgeons' outcome scoring was 4.49 ± 0.31. CONCLUSIONS: Superciliary arch augmentation with silicone implants is a quite simple, effective, inexpensive, and safe strategy to improve the three-dimensionality and contour of the upper face in East Asians.