Upconversion (UC) materials are renowned for their ability to convert low-energy photons into high-energy ones. The manipulation of parameters allows for the observation of multicolored UC luminescence (UCL) within a single material system. While modulation of multicolored UCL commonly relies on excitation at approximately 980â nm, investigation into multicolored UC materials activated by a 1532â nm excitation source remains comparatively scarce. In this work, we introduce NaLnF4:Er3+ as a novel class of smart luminescent materials. When the power density of a 1532â nm laser increases from 0.5 to 20.0â W/cm2, the emission peak positions remain unchanged, but the red-to-green (R/G) ratio decreases significantly from 18.82 to 1.48, inducing a color shift from red to yellow and ultimately to green. In contrast, no color variation is observed when NaLnF4:Er3+ is excited with a 980â nm laser at different power densities. This power-dependent multicolored UCL of NaLnF4:Er3+ excited at 1532â nm can be attributed to the competitive processes of upward pumping and downward relaxation of electrons on the 4I9/2 level of Er3+. By utilizing the unique UC characteristics of NaLnF4:Er3+, its potential utility in anti-counterfeiting applications is demonstrated. Our research highlights the distinctive optical properties of NaLnF4:Er3+ and provides novel insights into the use of luminescent materials in optical anti-counterfeiting technologies.
BACKGROUND AND AIMS: We aimed to examine the association between nutritional status, assessed by height/length and body weight for age and sex, and Epstein-Barr virus (EBV) viremia in children underwent liver transplantation. METHODS: Nutritional status was determined by total score of age- and sex-specific height/length and body weight: < (-2 SD) as "2 points", (-2 SD to -1 SD) as "1 point", and ≥ (-1SD) as "0 point". Children were further classified into three groups: malnutrition (4 points), risk of malnutrition (1-3 points), and normal (0 point). EBV viremia were confirmed by real time quantitative PCR method if EBV burden was ≥400 copies/ml. RESULTS: A total number of 896 children (414 boys and 482 girls, medium age 8 months) were included in the study. The medium height was 65.0 cm while medium body weight was 7.0 kg. The prevalence of EBV viremia was 54.6% during follow up. Comparing with children with normal nutritional status, the adjusted odds ratios for the risk of EBV viremia was 2.14 (95% CI: 1.44, 3.19) in children with risk of malnutrition, and 2.29 (95% CI: 1.54, 3.40) in children with malnutrition. Each point increase of nutritional score was associated with a 21% higher risk of EBV viremia (odd ratios = 1.21; 95% CI: 1.10, 1.34) in fully adjusted model. CONCLUSIONS: Nutritional score was associated with EBV viremia in children underwent liver transplantation.
Epstein-Barr Virus Infections , Herpesvirus 4, Human , Liver Transplantation , Nutritional Status , Viremia , Humans , Female , Male , Cross-Sectional Studies , Retrospective Studies , Infant , Child, Preschool , Child , Malnutrition , Body Weight , Prevalence , Body Height , Risk Factors
Non-infectious uveitis is an intraocular autoimmune disease mainly characterized by immune dysregulation of the eye, which may cause blindness if not well treated. Interleukin 10 (IL-10) is a potent cytokine with multiple immunoregulatory functions. However, it's in vivo activity is unstable owing to its inherent protein instability and short plasma half-life. Therefore, our previous research tried to establish IL-10-overexpressing MSC-sEVs (sEVs-IL10) using lentiviral transfection. While this approach indeed improved drug delivery, it also suffered from tedious procedures and limited loading efficiency. Accordingly, we constructed a novel MSC-sEVs-based delivery system for IL-10 (IL-10@sEVs) by sonication. The obtained formulation (IL-10@sEVs) had relatively higher loading efficiency and exerted a more profound immunomodulatory effect than sEVs-IL10 in vitro. Furthermore, IL-10@sEVs had significant therapeutic effects in a mouse model of experimental autoimmune uveitis (EAU) by decreasing the percentage of Th17 cells, increasing regulatory T cells in the eye, and draining lymph nodes. In summary, sonication outperforms conventional transfection methods for loading IL-10 into MSC-sEVs.
The underlying mechanisms between polycyclic aromatic hydrocarbons (PAHs) exposure and arterial stiffness are poorly understood. We carried out a panel study involving three repeated surveys to examine the associations of individual and mixture of PAHs exposure with arterial stiffness-related miRNAs among 123 community adults. In linear mixed-effect (LME) models, we found that urinary 9-hydroxyfluorene (9-OHFlu), 2-hydroxyphenanthrene (2-OHPh), 9-hydroxyphenanthrene (9-OHPh) at lag 0â¯day were positively linked to miR-146a and/or miR-222. The Bayesian kernel machine regression (BKMR) analyses revealed positive overall associations of PAHs mixture at lag 0â¯day with miR-146a and miR-222, and urinary 9-OHFlu contributed the most. In addition, an inter-quartile range (IQR) increase in urinary 9-OHFlu at lag 0â¯day was associated with elevated miR-146a and miR-222 by 0.16 (95% CI: 0.02, 0.30) to 0.34 (95% CI: 0.13, 0.54). Accordingly, exposure to PAHs, especially 9-OHFlu at lag 0â¯day, was related to elevated arterial stiffness-related plasma miRNAs.
OBJECTIVES: To prospectively investigate the associations of longitudinal changes in sleep score and LTPA and their combination with all-cause mortality. METHODS: Among 12,543 participants (mean age: 66.1 years) from the Dongfeng-Tongji cohort, we calculated sleep score (range, 0-4, integrating bedtime, sleep duration, sleep quality, and midday napping, higher score indicating healthier sleep) and LTPA at baseline (2008-2010) and the first follow-up (2013) surveys and their 5-year changes (defining stable sleep score as no change and stable LTPA as change within 150 min/week). We prospectively documented deaths from the first follow-up survey (2013) through December 31, 2018. RESULTS: During a mean 5.5-year follow-up, 792 deaths occurred. The 5-year changes in sleep score and LTPA were inversely associated with all-cause mortality risk, regardless of their initial values. When assessing 5-year changes in sleep score and LTPA jointly, compared with the stable sleep score-stable LTPA group, the decreased sleep score-decreased LTPA group had a 40 % (5-85 %) higher all-cause mortality risk, whereas the increased sleep score-increased LTPA group had a 34 % (9-52 %) lower risk. The direction of the joint association was mainly driven by sleep score change. Participants maintaining sleep scores ≥ 3 and LTPA ≥ 150 min/week over 5 years had a 44 % (28-56 %) lower all-cause mortality risk. CONCLUSIONS: Promoting sleep hygiene and LTPA together may benefit efforts in reducing mortality risk, with particular attention to monitoring long-term sleep health.
OBJECTIVE: Evidence regarding the modifying effect of the polygenic risk score (PRS) on the associations between glycemic traits and hearing loss (HL) was lacking. We aimed to examine whether these associations can be influenced by genetic susceptibility. RESEARCH DESIGN AND METHODS: This cross-sectional study included 13,275 participants aged 64.9 years from the Dongfeng-Tongji cohort. HL was defined according to a pure tone average >25 dB in the better ear and further classified by severity. Prediabetes and type 2 diabetes (T2D) were defined based on the 2013 criteria from the American Diabetes Association. A PRS was derived from 37 single-nucleotide polymorphisms associated with HL. Multivariable logistic regression models were fitted to estimate the associations of PRS and glycemic traits with HL and its severity. RESULTS: Elevated fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c), and T2D were positively associated with higher HL risks and its severity, with odds ratios (ORs) ranging from 1.04 (95% CI 1.00, 1.08) to 1.25 (95% CI 1.06, 1.46). We also found significant interaction between HbA1c and PRS on risks of overall HL and its severity (P for multiplicative interaction <0.05), and the effects of HbA1c on HL risks were significant only in high PRS. Additionally, compared with normoglycemia in the low PRS, T2D was respectively associated with an OR of up to 2.00 and 2.40 for overall HL and moderate to severe HL in the high PRS (P for additive interaction <0.05). CONCLUSIONS: PRS modifies the association of HbA1c with HL prevalence among middle-aged and older Chinese.
PURPOSE: We aimed to evaluate adalimumab efficacy in patients with initial-onset or recurrent Vogt-Koyanagi-Harada (VKH) syndrome. METHODS: A retrospective clinical study was performed to examine the therapeutic effect of adalimumab in 22 VKH patients,16 with initial-onset and six with recurrent VKH. Another 22 patients with initial-onset VKH who did not receive adalimumab were included as controls. The main observational parameters included the central macular thickness (CMT), subfoveal choroidal thickness (SCT), best-corrected visual acuity (BCVA), anterior chamber cell grade (ACC), glucocorticoid dose (GCD), and the development of sunset glow fundus. MRNA sequencing was used to profile the tumor necrosis factor (TNF)-α pathway in peripheral blood mononuclear cells obtained from nine patients with initial-onset VKH disease, six patients with recurrent VKH, and eight healthy controls. RESULTS: In the initial-onset group, adalimumab therapy significantly improved the BCVA, CMT, SCT, and ACC. Furthermore, adalimumab significantly decreased GCD in patients with initial-onset. In patients with recurrent VKH, the SCT significantly improved after adalimumab treatment, but no significant changes in BCVA, CMT, and ACC were observed. All six patients experienced relapse during follow-up. The TNF-α pathway exhibited a significant increase in initial-onset VKH when compared with that in both healthy controls and recurrent patients. Conversely, it was suppressed in recurrent VKH when compared with that in the initial-onset or healthy control groups. CONCLUSIONS: In patients with initial-onset VKH, adalimumab effectively reduces glucocorticoid dependence. However, adalimumab may not be effective for preventing relapse or providing long-term inflammation relief in patients with recurrent VKH.
Background: Neoadjuvant chemotherapy plus immunotherapy (nCT + ICIs) and neoadjuvant chemoradiotherapy plus immunotherapy (nCRT + ICIs) both induced favorable pathological response and tolerant toxicities for locally resectable esophageal squamous cell carcinoma (ESCC). However, few studies compared safety and efficacy between the two treatment strategies. Methods: This retrospective study collected clinical data of locally resectable ESCC patients who underwent nCT + ICIs or nCRT + ICIs followed by esophagectomy from November 2019 to December 2022. The incidence of adverse events, surgical outcomes, short and long-term efficacy, and treatment costs were compared. Results: A total of 206 patients were included, with a ratio of 158:48 between nCT + ICIs group and nCRT + ICIs group. The two groups exhibited well-balanced baseline characteristics. Most adverse events were grade 1-2 in both groups. The nCT + ICIs group had a longer operative time (334.00 ± 170.2 min vs 279.60 ± 88.31 min, P=0.020) than nCRT + ICIs group, but there were no differences in surgical complications. Although nCT + ICIs group had a lower pCR rate (32.3% vs 52.1%, P=0.004), the 2-year overall survival (84.42% vs 81.70%, P=0.860), 2-year disease-free survival (83.21% vs 80.47%, P=0.839), and recurrence patterns were similar to nCRT + ICIs group. In addition, nCT + ICIs group had significantly lower expenses (188796.00 ± 107704.00 RMB vs 231808.00 ± 48067.00 RMB, P=0.045). Conclusion: Overall, nCT + ICIs have comparable safety and efficacy compared to nCRT + ICIs for locally resectable ESCC, but with lower hospitalization costs.
Chemoradiotherapy , Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Esophagectomy , Immunotherapy , Neoadjuvant Therapy , Humans , Male , Esophageal Squamous Cell Carcinoma/therapy , Esophageal Squamous Cell Carcinoma/mortality , Female , Neoadjuvant Therapy/adverse effects , Neoadjuvant Therapy/methods , Middle Aged , Esophageal Neoplasms/therapy , Esophageal Neoplasms/mortality , Retrospective Studies , Chemoradiotherapy/methods , Chemoradiotherapy/adverse effects , Aged , Esophagectomy/adverse effects , Immunotherapy/methods , Immunotherapy/adverse effects , Treatment Outcome , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects
BACKGROUND: Autoimmune uveitis is an inflammatory disease triggered by an aberrant immune response. Mesenchymal stem cell-derived small extracellular vesicles (MSC-sEVs) are emerging as potential therapeutic agents for this condition. CD73, an ectoenzyme present on MSC-sEVs, is involved in mitigating inflammation by converting extracellular adenosine monophosphate into adenosine. We hypothesize that the inhibitory effect of MSC-sEVs on experimental autoimmune uveitis (EAU) could be partially attributed to the surface expression of CD73. METHODS: To investigate novel therapeutic approaches for autoimmune uveitis, we performed lentiviral transduction to overexpress CD73 on the surface of MSC-sEVs, yielding CD73-enriched MSC-sEVs (sEVs-CD73). Mice with interphotoreceptor retinoid-binding protein (IRBP)-induced EAU were grouped randomly and treated with 50 µg MSC-sEVs, vector infected MSC-sEVs, sEVs-CD73 or PBS via single tail vein injection. We evaluated the clinical and histological features of the induced mice and analyzed the proportion and functional capabilities of T helper cells. Furthermore, T-cells were co-cultured with various MSC-sEVs in vitro, and we quantified the resulting inflammatory response to assess the potential therapeutic benefits of sEVs-CD73. RESULTS: Compared to MSC-sEVs, sEVs-CD73 significantly alleviates EAU, leading to reduced inflammation and diminished tissue damage. Treatment with sEVs-CD73 results in a decreased proportion of Th1 cells in the spleen, draining lymph nodes, and eyes, accompanied by an increased proportion of regulatory T-cells (Treg cells). In vitro assays further reveal that sEVs-CD73 inhibits T-cell proliferation, suppresses Th1 cells differentiation, and enhances Treg cells proportion. CONCLUSION: Over-expression of CD73 on MSC-sEVs enhances their immunosuppressive effects in EAU, indicating that sEVs-CD73 has the potential as an efficient immunotherapeutic agent for autoimmune uveitis.
5'-Nucleotidase , Autoimmune Diseases , Extracellular Vesicles , Mesenchymal Stem Cells , Uveitis , Animals , Uveitis/pathology , Uveitis/therapy , Uveitis/metabolism , Uveitis/immunology , 5'-Nucleotidase/metabolism , 5'-Nucleotidase/genetics , Extracellular Vesicles/metabolism , Mesenchymal Stem Cells/metabolism , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/immunology , Mice , Autoimmune Diseases/therapy , Autoimmune Diseases/pathology , Autoimmune Diseases/immunology , Mice, Inbred C57BL , Disease Models, Animal , Female , Retinol-Binding Proteins , Humans
Acute lung injury (ALI) poses a significant medical challenge due to its widespread occurrence and high mortality rates. Despite extensive efforts, current clinical interventions for ALI have shown limited success. Inflammation plays a central role within ALI progress, and boric acid (BA) has demonstrated anti-inflammatory properties both in vitro and in vivo. However, its potential to mitigate lipopolysaccharide (LPS)-induced ALI remains an area awaiting exploration in research. To bridge this research gap, we created a mouse model of ALI induced by intraperitoneal LPS injection. We employed a comprehensive set of evaluation criteria, including H&E staining, wet/dry ratio measurement, malondialdehyde (MDA)/superoxide dismutase (SOD) the oxidative stress-related biomarkers, assessment of alveolar edema, hemorrhage, inflammatory cell infiltration, and examination of thickened alveolar septum to quantify lung injury. Additionally, we measured inflammatory cytokine levels using ELISA and assessed Nrf2 and HO-1 expressions through western blotting and quantitative real-time PCR (RT-PCR). ER stress-related markers (GRP78, CHOP) were analyzed through western blot analysis. Our findings revealed that prophylactic treatment with BA effectively attenuated LPS-induced ALI, as supported by improved pathological alterations, decreased total protein concentration in bronchoalveolar lavage fluid (BALF), and reduced pulmonary edema. Furthermore, BA exhibited anti-inflammatory properties by suppressing inflammatory cytokines within the lung tissue. BA ingestion caused upregulation in SOD and a decrease in MDA contents in lung tissue homogenates. BA downregulated the levels of GRP78 and CHOP compared to the LPS group. Remarkably, BA also upregulated transcription and protein expression of Nrf2 and HO-1 compared to the LPS group. In conclusion, our study highlights BA's potential as a novel promising prophylactic agent for LPS-induced ALI, offering avenue for improving clinical management of this condition.
Solid oxide electrolysis cells are prospective approaches for CO2 utilization but face significant challenges due to the sluggish reaction kinetics and poor stability of the fuel electrodes. Herein, we strategically addressed the long-standing trade-off phenomenon between enhanced exsolution and improved structural stability via topotactic ion exchange. The surface dynamic reconstruction of the MnOx/La0.7Sr0.3Cr0.9Ir0.1O3-δ (LSCIr) catalyst was visualized at the atomic scale. Compared with the Ir@LSCIr interface, the in situ self-assembled Ir@MnOx/LSCIr interface exhibited greater CO2 activation and easily removable carbonate intermediates, thus reached a 42% improvement in CO2 electrolysis performance at 1.6 V. Furthermore, an improved CO2 electrolysis stability was achieved due to the uniformly wrapped MnOx shell of the Ir@MnOx/LSCIr cathode. Our approach enables a detailed understanding of the dynamic microstructure evolution at active interfaces and provides a roadmap for the rational design and evaluation of efficient metal/oxide catalysts for CO2 electrolysis.
OBJECTIVE: To assess the effects of timing of maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination status on placental transfer of antibodies to neonates. METHODS: In this cross-sectional study, chemiluminescence was employed to measure SARS-CoV-2 IgG antibody titers in paired maternal-infant samples from women infected during pregnancy who were vaccinated or unvaccinated. Generalized linear regression assessed factors affecting antibody transfer in infected pregnant women and neonatal titers. RESULTS: The group with ≥90 days between infection and delivery showed a higher antibody transfer rate than the <90 days group(ß= 0.33, 95%CI: 0.01-0.65). Neonatal IgG titers correlated significantly with maternal titers and with maternal infections more than 90 days before delivery. Among infected pregnant women, those who had received two or three doses of vaccine before pregnancy had higher neonatal antibody titers than those who were not vaccinated (ßâ¯=â¯57.70, 95%CI: 31.33-84.07). CONCLUSION: Neonates born to pregnant women who were vaccinated before infection showed higher antibody titers than neonates of pregnant women who were not vaccinated before infection. The transfer rate is higher in pregnant women with ≥90 days from infection to delivery than in those with <90 days. These findings highlight the importance of timely maternal vaccination to optimize maternal and infant immunity.
OBJECTIVE: This study aims to explore the mechanisms underlying exercise commitment, exercise atmosphere, exercise self-efficacy, and exercise adherence among college students, as well as the impact of gender differences on these mechanisms. METHODS: Using a stratified cluster sampling method, 984 college students (aged 19.74 ± 1.25 years) from six universities in Anhui, Shandong, and Shaanxi provinces were randomly selected, with 403 male students and 581 female students. They had completed the Exercise Commitment Scale (ECC), Physical Exercise Atmosphere Scale (PEAS), Exercise Self-Efficacy Scale (ESES), and Exercise Adherence Scale (EPS). The study variables were analyzed in sequence for reliability and validity, correlation analysis, regression analysis, structural equation model testing, and bias-corrected percentile Bootstrap testing using SPSS 23.0 software and Hayes' (2013) Process plug-in. RESULTS: Exercise commitment significantly positively predicted exercise adherence (ß = 0.796, p < 0.01), exercise commitment significantly positively predicted exercise environment and exercise self-efficacy (ß = 0.645, p < 0.01, ß = 0.356, p < 0.01), exercise environment significantly positively predicted exercise self-efficacy and exercise adherence (ß = 0.344, p < 0.01, ß = 0.144, p < 0.01), and exercise self-efficacy significantly positively predicted exercise adherence (ß = 0.934, p < 0.01). The mediating role of exercise environment in the relationship between exercise commitment and exercise adherence does not exist in male college students, while it exists in female college students. CONCLUSIONS: Exercise atmosphere and exercise self-efficacy play a mediating role between exercise commitment and exercise adherence, with a total mediating effect value of 0.796. This study indicates that exercise commitment not only directly predicts exercise adherence, but also indirectly predicts exercise adherence through the chained mediating effects of exercise atmosphere and exercise self-efficacy. The above-mentioned mediating effect exists in female college students, while some mediating effects do not exist in male college students, thus gender has a significant impact on this mediating effect.
Exercise , Self Efficacy , Students , Humans , Male , Female , Exercise/physiology , Students/psychology , Young Adult , Universities , Adolescent , Sex Factors , Surveys and Questionnaires , Adult
Introduction: Neonatal hypoxic-ischemic brain damage (HIBD) refers to brain damage in newborns caused by hypoxia and reduced or even stopped cerebral blood flow during the perinatal period. Currently, there are no targeted treatments for neonatal ischemic hypoxic brain damage, primarily due to the incomplete understanding of its pathophysiological mechanisms. Especially, the role of NMDA receptors is less studied in HIBD. Therefore, this study explored the molecular mechanism of endogenous protection mediated by GluN2B-NMDAR in HIBD. Method: Hypoxic ischemia was induced in mice aged 9-11 days. The brain damage was examined by Nissl staining and HE staining, while neuronal apoptosis was examined by Hoechst staining and TTC staining. And cognitive deficiency of mice was examined by various behavior tests including Barnes Maze, Three Chamber Social Interaction Test and Elevated Plus Maze. The activation of ER stress signaling pathways were evaluated by Western blot. Results: We found that after HIBD induction, the activation of GluN2B-NMDAR attenuated neuronal apoptosis and brain damage. Meanwhile, the ER stress PERK/eIF2α signaling pathway was activated in a time-dependent manner after HIBE. Furthermore, after selective inhibiting GluN2B-NMDAR in HIBD mice with ifenprodil, the PERK/eIF2α signaling pathway remains continuously activated, leading to neuronal apoptosis, morphological brain damage. and aggravating deficits in spatial memory, cognition, and social abilities in adult mice. Discussion: The results of this study indicate that, unlike its role in adult brain damage, GluN2B in early development plays a neuroprotective role in HIBD by inhibiting excessive activation of the PERK/eIF2α signaling pathway. This study provides theoretical support for the clinical development of targeted drugs or treatment methods for HIBD.
Importance: The associations of changes in sleep patterns with incident cardiovascular disease (CVD) are not fully elucidated, and whether these associations are modified by genetic susceptibility remains unknown. Objectives: To investigate the associations of 5-year changes in sleep patterns with incident CVD and whether genetic susceptibility modifies these associations. Design, Setting, and Participants: This prospective cohort study of the Dongfeng-Tongji cohort was conducted from 2008 to 2018 in China. Eligible participants included those with complete sleep information at baseline survey (2008-2010) and the first follow-up survey (2013); participants who had no CVD or cancer in 2013 were prospectively assessed until 2018. Statistical analysis was performed in November 2023. Exposures: Five-year changes in sleep patterns (determined by bedtime, sleep duration, sleep quality, and midday napping) between 2008 and 2013, and polygenic risk scores (PRS) for coronary heart disease (CHD) and stroke. Main Outcomes and Measures: Incident CVD, CHD, and stroke were identified from 2013 to 2018. Cox proportional hazards regression models were applied to estimate hazard ratios (HRs) and 95% CIs. Results: Among 15â¯306 individuals (mean [SD] age, 65.8 [7.4] years; 8858 [57.9%] female and 6448 male [42.1%]), 5474 (35.78%) had persistent unfavorable sleep patterns and 3946 (25.8%) had persistent favorable sleep patterns. A total of 3669 incident CVD cases were documented, including 2986 CHD cases and 683 stroke cases, over a mean (SD) follow-up of 4.9 (1.5) years. Compared with those with persistent unfavorable sleep patterns, individuals with persistent favorable sleep patterns over 5 years had lower risks of incident CVD (HR, 0.80; 95% CI, 0.73-0.87), CHD (HR, 0.84; 95% CI, 0.76-0.92), and stroke (HR, 0.66; 95% CI, 0.54-0.82) in the subsequent 5-year period. No significant effect modification by PRS was observed for sleep pattern change and CHD or stroke risk. However, sleep pattern changes and PRS were jointly associated with the CHD and stroke risk in a dose-dependent manner, with the lowest risk being among those with persistent favorable sleep patterns combined with low PRS (HR for CHD, 0.65; 95% CI, 0.52-0.82 and HR for stroke, 0.48; 95% CI, 0.29-0.79). Conclusions and Relevance: In this cohort study of middle-aged and older Chinese adults, individuals with persistent favorable sleep patterns had a lower CVD risk, even among those with higher genetic risk. These findings highlight the importance of maintaining favorable sleep patterns for CVD prevention.
Cardiovascular Diseases , Genetic Predisposition to Disease , Sleep , Humans , Male , Female , China/epidemiology , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/genetics , Aged , Middle Aged , Prospective Studies , Sleep/physiology , Incidence , Risk Factors , Proportional Hazards Models
Idiopathic uveitis (IU) and Vogt-Koyanagi-Harada (VKH) syndrome are common types of uveitis. However, the exact pathological mechanisms of IU and VKH remain unclear. Proteomic analysis of aqueous humor (AH), the most easily accessible intraocular fluid and a key site of uveitis development, may reveal potential biomarkers and elucidate uveitis pathogenesis. In this study, 44 AH samples, including 12 IU cases, 16 VKH cases, and 16 controls, were subjected to label-free quantitative proteomic analysis. We identified 557 proteins from a comprehensive spectral library of 634 proteins across all samples. The AH proteomic profiles of the IU and VKH groups were different from those of the control group. Differential analysis revealed a shared pattern of extracellular matrix disruption and downregulation of retinal cellular proteins in the IU and VKH groups. Enrichment analysis revealed a protein composition indicative of inflammation in the AH of the IU and VKH groups but not in that of the control group. In the IU and VKH groups, innate immunity played an important role, as indicated by complement cascade activation and overexpression of innate immune cell markers. Extreme gradient boosting (XGBoost), an efficient and robust machine learning algorithm, was subsequently used to screen potential biomarkers for classifying the IU, VKH, and control groups. Transferrin and complement factor B were deemed the most important and represent a promising biomarker panel. These proteins were validated by high-resolution multiple reaction monitoring (HR-MRM) in an independent validation cohort. A classification decision tree was subsequently built for the diagnosis. Our findings further the understanding of the underlying molecular mechanisms in IU and VKH and facilitate the development of potential therapeutic and diagnostic strategies.
Lanthanide-doped upconversion (UC) materials have been extensively investigated for their unique capability to convert low-energy excitation into high-energy emission. Contrary to previous reports suggesting that efficient UC luminescence (UCL) is exclusively observed in materials with a wide bandgap, we have discovered in this study that Y2Mo4O15:Yb3+/Tm3+ microcrystals, a narrowband material, exhibit highly efficient UC emission. Remarkably, these microcrystals do not display any four- or five-photon UC emission bands. This particular optical phenomenon is independent of the variation in doping ion concentration, temperature, phonon energy, and excitation power density. Combining theoretical calculations and experimental results, we attribute the vanishing emission bands to the strong interaction between the bandgap of the Y2Mo4O15 host matrix (3.37â eV) and the high-energy levels (1I6 and 1D2) of Tm3+ ions. This interaction can effectively catalyze the UC emission process of Tm3+ ions, which leads to Y2Mo4O15:Yb3+/Tm3+ microcrystals possessing very strong UCL intensity. The brightness of these microcrystals outshines commercial UC NaYF4:Yb3+,Er3+ green phosphors by a factor of 10 and is 1.4 times greater than that of UC NaYF4:Yb3+,Tm3+ blue phosphors. Ultimately, Y2Mo4O15:Yb3+/Tm3+ microcrystals, with their distinctive optical characteristics, are being tailored for sophisticated anti-counterfeiting and information encryption applications.
BACKGROUND: Previous studies have demonstrated that early intervention was the best plan to inhibit the progression of Alzheimer's disease (AD), which relied on the discovery of early diagnostic biomarkers. In this study, synaptic vesicle glycoprotein 2 A (SV2A) was examined to improve the early diagnostic efficiency in AD. METHODS: In this study, biomarker testing was performed through the single-molecule array (Simoa). A total of 121 subjects including cognitively unimpaired controls, amnestic mild cognitive impairment (aMCI), AD and other types of dementia underwent cerebrospinal fluid (CSF) SV2A testing; 430 subjects including health controls, aMCI, AD and other types of dementia underwent serum SV2A, glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL) and p-tau217 testing; 92 subjects including aMCI and AD underwent both CSF SV2A and serum SV2A testing; 115 cognitively unimpaired subjects including APOE ε4 carriers and APOE ε4 non-carriers were tested for serum SV2A, GFAP, NfL and p-tau217. Then, the efficacy of SV2A for the early diagnosis of AD and its ability to identify those at high risk of AD from a cognitively unimpaired population were further analyzed. RESULTS: Both CSF and serum SV2A significantly and positively correlated with cognitive performance in patients with AD, and their levels gradually decreased with the progression of AD. Serum SV2A demonstrated excellent diagnostic efficacy for aMCI, with a sensitivity of 97.8%, which was significantly higher than those of NfL, GFAP, and p-tau217. The SV2A-positive rates ranged from 92.86 to 100% in aMCI cases that were negative for the above three biomarkers. Importantly, of all the biomarkers tested, serum SV2A had the highest positivity rate (81.82%) in individuals at risk for AD. CONCLUSIONS: Serum SV2A was demonstrated to be a novel and ideal biomarker for the early diagnosis of AD, which can effectively distinguish those at high risk of AD in cognitively unimpaired populations.
Alzheimer Disease , Membrane Glycoproteins , Nerve Tissue Proteins , Humans , Alzheimer Disease/diagnosis , Alzheimer Disease/genetics , Apolipoprotein E4 , Biomarkers , Early Diagnosis , Glycoproteins , Synaptic Vesicles/chemistry , Synaptic Vesicles/metabolism , Membrane Glycoproteins/cerebrospinal fluid , Membrane Glycoproteins/chemistry , Nerve Tissue Proteins/cerebrospinal fluid , Nerve Tissue Proteins/chemistry
BACKGROUND: The combination of programmed cell death protein-1 (PD-1) inhibitor and chemotherapy is approved as a standard first- or second-line treatment in patients with advanced oesophageal or gastric cancer. However, it is unclear whether this combination is superior to chemotherapy alone. AIM: To assess the comparative effectiveness and tolerability of combining PD-1 inhibitors with chemotherapy vs chemotherapy alone in patients with advanced gastric cancer, gastroesophageal junction (GEJ) cancer, or oesophageal carcinoma. METHODS: We searched the PubMed and Embase databases for studies that compared the efficacy and tolerance of PD-1 inhibitors in combination with chemotherapy vs chemotherapy alone in patients with advanced oesophageal or gastric cancer. We employed either random or fixed models to analyze the outcomes of each clinical trial, encompassing data on overall survival (OS), progression-free survival (PFS), objective response rate, and adverse events (AEs). RESULTS: Nine phase 3 clinical trials (7016 advanced oesophageal and gastric cancer patients) met the inclusion criteria. Our meta-analysis demonstrated that the pooled PD-1 inhibitor + chemotherapy group had a significantly longer OS than the chemotherapy-alone group [hazard ratio (HR) = 0.76, 95% confidence interval (CI): 0.71-0.81]; the pooled PFS result was consistent with that of OS (HR = 0.67, 95%CI: 0.61-0.74). The count of patients achieving an objective response in the PD-1 inhibitor + chemotherapy group surpassed that of the chemotherapy-alone group [odds ratio (OR) = 1.86, 95%CI: 1.59-2.18]. AE incidence was also higher in the combination-therapy group than in the chemotherapy-alone group, regardless of whether ≥ grade 3 only (OR = 1.30, 95%CI: 1.07-1.57) or all AE grades (OR = 1.88, 95%CI: 1.39-2.54) were examined. We performed a subgroup analysis based on the programmed death-ligand 1 (PD-L1) combined positive score (CPS) and noted extended OS and PFS durations within the CPS ≥ 1, CPS ≥ 5, and CPS ≥ 10 subgroups of the PD-1 inhibitor + chemotherapy group. CONCLUSION: In contrast to chemotherapy alone, the combination of PD-1 inhibitor and chemotherapy appears to present a more favorable option for initial or subsequent treatment in patients with gastric cancer, GEJ tumor, or oesophageal cancer. This holds true particularly for individuals with PD-L1 CPS scores of ≥ 5 and ≥ 10.
