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1.
ACS Photonics ; 11(9): 3730-3740, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39310302

RESUMEN

Recent years have seen the rapid development of miniaturized reconstructive spectrometers (RSs), yet they still confront a range of technical challenges, such as bandwidth/resolution ratio, sensing speed, and/or power efficiency. Reported RS designs often suffer from insufficient decorrelation between sampling channels, which, in essence, is due to inadequate engineering of sampling responses. This in turn results in poor spectral-pixel-to-channel ratios (SPCRs), typically restricted at single digits. So far, there lacks a general guideline for manipulating RS sampling responses for the effectiveness of spectral information acquisition. In this study, we shed light on a fundamental parameter from the compressive sensing (CS) theory-the average mutual correlation coefficient ν-and provide insight into how it serves as a critical benchmark in RS design. To this end, we propose a novel RS design with multiresonant cavities, consisting of a series of partial reflective interfaces. Such multicavity configuration allows the superlative optimization of sampling matrices to achieve minimized ν. Experimentally, we implement a single-shot, dual-band RS on a SiN platform, realizing an overall operation bandwidth of 270 nm and a <0.5 nm resolution with only 15 sampling channels per band. This leads to a record high SPCR of 18.0. Moreover, the proposed multicavity design can be readily adapted to various photonic platforms, ranging from optical fibers to free-space optics. For instance, we showcase that by employing multilayer coatings, an ultrabroadband RS can be optimized to exhibit a 700 nm bandwidth with an SPCR of over 100.

2.
J Chem Phys ; 161(12)2024 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-39324531

RESUMEN

We introduce a Python package based on matrix product states (MPS) to simulate both the time-dependent Schrödinger equation (TDSE) and the hierarchical equations of motion (HEOM). The wave function in the TDSE or the reduced density operator/auxiliary density operators in the HEOM are represented using MPS. A matrix product operator (MPO) is then constructed to represent the Hamiltonian in the TDSE or the generalized Liouvillian in the HEOM. The fourth-order Runge-Kutta method and the time-dependent variational principle are used to propagate the MPS. Several examples, including the nonadiabatic interconversion dynamics of the pyrazine molecule, excitation energy transfer dynamics in molecular aggregates and photosynthetic light-harvesting complexes, the spin-boson model, a laser driven two-state model, the Holstein model, and charge transport in the Anderson impurity model, are presented to demonstrate the capability of the package.

3.
Artículo en Inglés | MEDLINE | ID: mdl-39280840

RESUMEN

Background: Acid-sensing ion channel 1a (ASIC1a) plays a critical role in physiological and pathological processes. To further elucidate the biological functions of ASICs and their relationships with disease occurrence and development, it is advantageous to investigate and develop additional regulatory factors for ASICs. Methods: In this study, cation exchange chromatography was used to separate seven chromatographic components from Naja naja atra venom. Capillary electrophoresis was employed to detect that Ⅶ peak component containing a main protein Ⅶ-2, which could bind to ASIC1a. The analgesic effects of Ⅶ-2 protein were determined using hot plate methods, and ASIC1a expression in spinal cord tissue from rats with inflammatory pain was detected using western blot. Results: The purified Ⅶ-2 protein named Naja naja atra venom-Ⅶ-2 (NNAV-Ⅶ-2) was obtained by Sephadex G-50 gel filtration, which exhibited a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis with a molecular weight of 6.7 kD. Remarkably, the NNAV-Ⅶ-2 protein demonstrated a significant analgesic effect and downregulated ASIC1a expression in the spinal cord tissue of rats with inflammatory pain. Conclusions: The analgesic mechanism of the NNAV-Ⅶ-2 protein may be associated with its binding to ASIC1a, consequently downregulating ASIC1a expression in neural tissues.

4.
J Affect Disord ; 367: 184-192, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39218312

RESUMEN

BACKGROUND: Despite substantial evidence regarding independent associations between physical activity (PA) and ultra-processed foods (UPF) consumption with depression, the joint effects of these two factors remain unknown. METHODS: This study included 99,126 participants without depression in the UK Biobank at baseline. A 24-h recall method was used to assess UPF consumption, and self-reported total physical activity (TPA), moderate-to-vigorous physical activity (MVPA), and vigorous physical activity (VPA) were assessed by metabolic equivalent task (MET). A series of Cox proportional hazard regression models were used to explore the independent and joint effects of TPA, MVPA, VPA and UPF consumption on depression. RESULTS: The incidence rate of depression was 1.94 % [95 % confidence interval (CI): 1.80 %-2.10 %] per 1000 person-years after an average follow-up of 12.10 years. We found that MVPA and UPF consumption had additive interactions on depression risk (p < 0.05). Participants in Q1 of TPA and Q4 of UPF consumption (HR: 1.83, 95%CI: 1.45-2.31) showed a higher risk for depression than those in Q4 of TPA and Q1 of UPF consumption. Compared with the participants with WHO guideline-recommended MVPA and the lowest UPF consumption, those below recommended MVPA (HR: 1.51, 95%CI: 1.20-1.89) or above recommended MVPA (HR: 1.40, 95%CI: 1.10-1.78) and with the highest UPF consumption had a higher risk for depression. LIMITATIONS: Study limitations include use of self-reported data, observational study and concerns regarding generalizability. CONCLUSION: Higher UPF consumption, accompanied by lower PA levels regardless of TPA, MVPA, and VPA, is associated with a higher risk of depression. Our study offers insights on public health priorities to decrease the risk of depression in the population by addressing both PA and UPF consumption together.

5.
Front Pharmacol ; 15: 1389140, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39263571

RESUMEN

Background: Vancomycin-associated acute kidney injury (AKI) leads to underestimated morbidity in the intensive care unit (ICU). It is significantly important to predict its occurrence in advance. However, risk factors and nomograms to predict this AKI are limited. Methods: This was a retrospective analysis of two databases. A total of 1,959 patients diagnosed with AKI and treated with vancomycin were enrolled from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. According to the 7:3 ratio, the training set (n = 1,372) and the internal validation set (n = 587) were randomly allocated. The external validation set included 211 patients from the eICU Collaborative Research Database (eICU). Next, to screen potential variables, the least absolute shrinkage and selection operator (LASSO) regression was utilized. Subsequently, the nomogram was developed by the variables of the selected results in the multivariable logistic regression. Finally, discrimination, calibration, and clinical utility were evaluated to validate the nomogram. Results: The constructed nomogram showed fine discrimination in the training set (area under the receiver operator characteristic curve [AUC] = 0.791; 95% confidence interval [CI]: 0.758-0.823), internal validation set (AUC = 0.793; 95% CI: 0.742-0.844), and external validation set (AUC = 0.755; 95% CI: 0.663-0.847). Moreover, it also well demonstrated calibration and clinical utility. The significant improvement (P < 0.001) in net reclassification improvement (NRI) and integrated differentiation improvement (IDI) confirmed that the predictive model outperformed others. Conclusion: This established nomogram indicated promising performance in determining individual AKI risk of vancomycin-treated critical care patients, which will be beneficial in making clinical decisions.

6.
J Affect Disord ; 367: 668-677, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39236888

RESUMEN

BACKGROUND: Many studies have shown that the COVID-19 pandemic has increased the risk of suicidal tendencies among the public. However, there is limited research reporting on the changing trends in suicidal ideation after 2020 in the context of the long-term normalization of COVID-19 prevention and control measures in China. METHODS: The self-administered online questionnaire was adopted to collect 12-month suicidal ideation, depressive symptoms, anxiety symptoms, stress, and some demographic information from university students by convenient cluster sampling in Shandong, Shaanxi, and Jilin Provinces, China. Multivariate logistic regressions were performed to assess the association between different factors and suicidal ideation. RESULTS: The prevalence of 12-month suicidal ideation from 2021 to 2023 among university students was 3.89 %, 5.81 %, and 4.33 %, respectively, showing a trend of first increasing and then decreasing. The trends presented a similar tendency in the subgroups according to gender, majors, and grades, except among urban freshman-year students. The associated factors of suicidal ideation were different among university students in different surveys. However, female gender, poor mental health, and depressive symptoms were linked to a higher risk of suicidal ideation. LIMITATIONS: More representative large-scale longitudinal studies should be used to monitor the suicidal behavior of university students. CONCLUSIONS: The prevalence of 12-month suicidal ideation among Chinese university students exhibited a pattern of initial increase followed by a subsequent decrease from 2021 to 2023. Despite the complete lifting of COVID-19 prevention and control measures in China, the prolonged three-year epidemic may have enduring adverse effects on university students, underscoring the ongoing importance of providing continuous mental health services to this population.

7.
Nano Lett ; 24(33): 10362-10371, 2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39133195

RESUMEN

Adoptive cell therapies for solid tumors are usually limited by off-target antigens, incapable tissue infiltration, and cell function exhaustion. In contrast, bacterial cells possess the inherent competencies of preferential tumor targeting, deep tissue penetration, and high intratumoral bioactivity and represent promising alternatives to overcome these challenges. Here, a sialic-acid-responsive regulatory gene circuit is engineered into Escherichia coli MG1655 to express cytolysin of hemolysin E (HlyE). Furthermore, sialidases are bioorthogonally decorated onto the surface of azido-functionalized bioengineered bacteria for recognizing tumor sialoglycans and cleaving their sialosides into free sialic acids. As chemical inducers, sialic acids feedbackingly activate the bacterial gene circuit to produce HlyE and lyse tumor cells. This study mimics the tumor antigen-induced cytotoxin production and cell lysis that occurs in chimeric antigen receptor T (CAR-T) cells yet surmounts the intrinsic limitations of adoptive cell therapies. Moreover, sialidase-mediated tumor cell desialylation also reverses the immunosuppressive effect of glycoimmune checkpoints and further improves the therapeutic effect of solid tumors.


Asunto(s)
Escherichia coli , Neoplasias , Neuraminidasa , Neuraminidasa/genética , Neuraminidasa/metabolismo , Humanos , Escherichia coli/genética , Animales , Neoplasias/terapia , Ratones , Línea Celular Tumoral , Proteínas Hemolisinas/química , Receptores Quiméricos de Antígenos/inmunología , Inmunoterapia Adoptiva
8.
Artículo en Inglés | MEDLINE | ID: mdl-39001888

RESUMEN

PURPOSE: To examine the dose‒response relationships of sedentary behavior (SB) and physical activities (PAs) with depression, and to explore the effects of replacing SB with PAs on depression risk. METHODS: The study used data from UK Biobank aged 37 to 73 years. Light physical activity (LPA), moderate-to-vigorous activity (MVPA), sleep duration, and total sedentary behavior (TSB) were measured by accelerometers. Self-reported SB was also adopted when daily screen-sedentary behavior time (SSB) and leisure-sedentary behavior time (LSB) were the focus. Incident depression was obtained from the part of mental and behavioral disorders in the "first occurrence fields" of UK Biobank. A Cox proportional hazard model and isotemporal substitution model were performed to explore the associations of LPA, MVPA, TSB, LSB, SSB, and sleep on depression and the effects of replacing SB time with equal PA time. RESULTS: Highest levels of MVPA (HR = 0.58, 95%CI: 0.50-0.68) were associated with decreased depression risk compared with the lowest level (Q1). Longer SSB time (HR = 1.18, 95%CI: 1.06-1.32), LSB time (HR = 1.19, 95%CI: 1.07-1.32), and TSB time (HR = 1.17, 95%CI: 1.00-1.38) could increase depression risk significantly. Replacing 1h/day TSB, SSB, and LSB with MVPA brought the greatest risk reductions [31% (HR = 0.69, 95%CI: 0.62-0.77), 30% (HR = 0.70, 95%CI: 0.65-0.77), and 29% (HR = 0.71, 95%CI: 0.65-0.77)]. Under the same conditions, the effects of LPA replacement were also significant, but weaker than those of MVPA. Subgroup analyses showed that replacing 1h/d TSB with LPA could significantly decrease the depression risk for the females, but not for the males. CONCLUSION: Large benefits for reducing the risk of incident depression could be attained by replacing a period of TSB, SSB, or LSB with equal PA time, especially for MVPA. Regular PA and less SB were recommended for improving mental health.

9.
J Phys Chem A ; 128(31): 6337-6350, 2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39047261

RESUMEN

Photoinduced excited-state energy transfer (EET) processes play an important role in solar energy conversions. Owing to their excellent photoharvesting and exciton-transport properties, phenylene ethynylene (PE) dendrimers display great potential for improving the efficiency of solar cells. In this work, we investigated the intramolecular EET dynamics in a dendrimer composed of two linear PE units (2-ring and 3-ring) using a fully quantum description based on the tensor network method. We first constructed a diabatic model Hamiltonian based on the electronic structure calculations. Using this diabatic vibronic coupling model, we tried to obtain the main features of the EET dynamics in terms of the several diabatic models with different numbers of vibrational modes (from 4 modes to 129 modes) and to explore the corresponding vibronic coupling interactions. The results show that the EET in this PE dendrimer is ultrafast. Four modes of A' symmetry play dominant roles in the dynamics; the remaining 86 modes of A' symmetry can dampen the electronic coherence; and the modes of A″ symmetry do not exhibit significant influence on the EET process. Overall, the first-order intrastate vibronic coupling terms show the dominant role in the EET dynamics, while the second-order intrastate vibronic coupling terms cause damping of the electronic coherence and slow down the overall EET process. This work provides a microscopic understanding of the EET dynamics in PE dendrimers.

10.
J Clin Hypertens (Greenwich) ; 26(8): 955-963, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38952049

RESUMEN

The E-proteinoid 3 receptor (PTGER3), a member of the prostaglandin E2 (PGE2) subtype receptor, belongs to the G-protein-coupled superfamily of receptors. Animal studies have demonstrated its involvement in salt sensitivity by regulating sodium reabsorption. This study aimed to investigate the association between genetic variants of PTGER3 and salt sensitivity, longitudinal blood pressure (BP) changes, and the incidence of hypertension in Chinese adults. A chronic salt intake intervention was conducted involving 514 adults from 124 families in the 2004 Baoji Salt-Sensitivity Study Cohort in northern China. These participants followed a 3-day regular baseline diet, followed by a 7-day low-salt diet (3.0 g/d) and a 7-day high-salt diet (18 g/d), and were subsequently followed for 14 years. The findings revealed a significant relationship between the single nucleotide polymorphism (SNP) rs17482751 of PTGER3 and diastolic blood pressure (DBP) response to high salt intervention. Additionally, SNPs rs11209733, rs3765894, and rs2268062 were significantly associated with longitudinal changes in systolic blood pressure (SBP), DBP, and mean arterial pressure (MAP) during the 14-year follow-up period. SNP rs6424414 was significantly associated with longitudinal changes in DBP over 14 years. Finally, SNP rs17482751 showed a significant correlation with the incidence of hypertension over 14 years. These results emphasize the significant role of PTGER3 gene polymorphism in salt sensitivity, longitudinal BP changes, and the development of hypertension in the Chinese population.


Asunto(s)
Presión Sanguínea , Hipertensión , Polimorfismo de Nucleótido Simple , Subtipo EP3 de Receptores de Prostaglandina E , Cloruro de Sodio Dietético , Humanos , Hipertensión/genética , Hipertensión/epidemiología , Hipertensión/fisiopatología , Masculino , Femenino , China/epidemiología , Incidencia , Adulto , Persona de Mediana Edad , Presión Sanguínea/genética , Presión Sanguínea/fisiología , Cloruro de Sodio Dietético/efectos adversos , Subtipo EP3 de Receptores de Prostaglandina E/genética , Estudios Longitudinales , Pueblo Asiatico/genética , Dieta Hiposódica/métodos , Pueblos del Este de Asia
11.
J Inflamm Res ; 17: 3967-3982, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38915807

RESUMEN

Background: Inflammation and cardiac fibrosis are important pathogenic drivers of heart failure. The fibrosis-4 index (FIB-4) is associated with a higher degree of fibrosis. The systemic immune inflammation index (SII) is associated with a higher degree of systemic inflammation status. Previous studies have shown that they are associated with a poor prognosis for cardiovascular disease. We sought to investigate the value of FIB-4 combined with the SII as a novel inflammation-fibrosis combined index (IFCI) in predicting left ventricular reverse remodeling (LVRR) and prognosis among reduced ejection fraction heart failure (HFrEF) patients. Methods: A total of 895 patients with HFrEF were continuously recruited. Receiver operating characteristic curves were drawn to assess the abilities of inflammation-fibrosis indicators to predict LVRR. Multivariable Cox regression analysis was used to examine independent predictors of composite cardiac events and all-cause death. Results: After six months of follow-up, 344 (38.4%) patients experienced LVRR. The IFCI had the largest area under the curve (0.835, P < 0.001). In multivariate-adjusted logistic regression analyses, FIB-4, SII, and IFCI were predictive of LVRR (P value < 0.05). The IFCI was associated with a 3.686-fold higher risk of non-LVRR (odds ratio [OR] = 3.686, P < 0.001). Moreover, an increased IFCI predicted a poor prognosis in HFrEF patients. The highest risk of composite cardiac events (hazard ratio [HR] = 2.716, P < 0.001) was observed in the top IFCI-tertile group, and similar results were found regarding independent risk indicators of all-cause death. Conclusion: In summary, this study indicated that increased IFCI at admission offers good predictability regarding non-LVRR and predicts the risk of all-cause mortality or composite cardiovascular events due to HFrEF patients and could be used as a novel marker.

12.
ACS Appl Mater Interfaces ; 16(24): 31843-31850, 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38841859

RESUMEN

Liquid crystal (LC) biosensors have received significant attention for their potential applications for point-of-care devices due to their sensitivity, low cost, and easy read-out. They have been employed to detect a wide range of important biological molecules. However, detecting the function of membrane proteins has been extremely challenging due to the difficulty of integrating membrane proteins, lipid membranes, and LCs into one system. In this study, we addressed this challenge by monitoring the proton-pumping function of bacteriorhodopsin (bR) using a pH-sensitive LC thin film biosensor. To achieve this, we deposited purple membranes (PMs) containing a 2D crystal form of bRs onto an LC-aqueous interface. Under light, the PM patches changed the local pH at the LC-aqueous interface, causing a color change in the LC thin film that is observable through a polarizing microscope with crossed polarizers. These findings open up new opportunities to study the biofunctions of membrane proteins and their induced local environmental changes in a solution using LC biosensors.


Asunto(s)
Bacteriorodopsinas , Técnicas Biosensibles , Cristales Líquidos , Técnicas Biosensibles/métodos , Cristales Líquidos/química , Concentración de Iones de Hidrógeno , Bacteriorodopsinas/química , Proteínas de la Membrana/química , Membrana Púrpura/química
13.
ACS Nano ; 18(20): 13266-13276, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38709874

RESUMEN

One key challenge in postoperative glioblastoma immunotherapy is to guarantee a potent and durable T-cell response, which is restricted by the immunosuppressive microenvironment within the lymph nodes (LNs). Here, we develop an in situ sprayed exosome-cross-linked gel that acts as an artificial LN structure to directly activate the tumor-infiltrating T cells for prevention of glioma recurrence. Briefly, this gel is generated by a bio-orthogonal reaction between azide-modified chimeric exosomes and alkyne-modified alginate polymers. Particularly, these chimeric exosomes are generated from dendritic cell (DC)-tumor hybrid cells, allowing for direct and robust T-cell activation. The gel structure with chimeric exosomes as cross-linking points avoids the quick clearance by the immune system and thus prolongs the durability of antitumor T-cell immunity. Importantly, this exosome-containing immunotherapeutic gel provides chances for ameliorating functions of antigen-presenting cells (APCs) through accommodating different intracellular-acting adjuvants, such as stimulator of interferon genes (STING) agonists. This further enhances the antitumor T-cell response, resulting in the almost complete elimination of residual lesions after surgery. Our findings provide a promising strategy for postsurgical glioma immunotherapy that warrants further exploration in the clinical arena.


Asunto(s)
Exosomas , Glioblastoma , Inmunoterapia , Ganglios Linfáticos , Exosomas/química , Glioblastoma/terapia , Glioblastoma/inmunología , Glioblastoma/patología , Humanos , Ganglios Linfáticos/inmunología , Ganglios Linfáticos/patología , Animales , Ratones , Geles/química , Células Dendríticas/inmunología , Linfocitos T/inmunología , Línea Celular Tumoral , Neoplasias Encefálicas/inmunología , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/patología , Ratones Endogámicos C57BL
14.
Signal Transduct Target Ther ; 9(1): 129, 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38740763

RESUMEN

The safety and efficacy of COVID-19 vaccines in the elderly, a high-risk group for severe COVID-19 infection, have not been fully understood. To clarify these issues, this prospective study followed up 157 elderly and 73 young participants for 16 months and compared the safety, immunogenicity, and efficacy of two doses of the inactivated vaccine BBIBP-CorV followed by a booster dose of the recombinant protein vaccine ZF2001. The results showed that this vaccination protocol was safe and tolerable in the elderly. After administering two doses of the BBIBP-CorV, the positivity rates and titers of neutralizing and anti-RBD antibodies in the elderly were significantly lower than those in the young individuals. After the ZF2001 booster dose, the antibody-positive rates in the elderly were comparable to those in the young; however, the antibody titers remained lower. Gender, age, and underlying diseases were independently associated with vaccine immunogenicity in elderly individuals. The pseudovirus neutralization assay showed that, compared with those after receiving two doses of BBIBP-CorV priming, some participants obtained immunological protection against BA.5 and BF.7 after receiving the ZF2001 booster. Breakthrough infection symptoms last longer in the infected elderly and pre-infection antibody titers were negatively associated with the severity of post-infection symptoms. The antibody levels in the elderly increased significantly after breakthrough infection but were still lower than those in the young. Our data suggest that multiple booster vaccinations at short intervals to maintain high antibody levels may be an effective strategy for protecting the elderly against COVID-19.


Asunto(s)
Anticuerpos Neutralizantes , Anticuerpos Antivirales , Vacunas contra la COVID-19 , COVID-19 , SARS-CoV-2 , Vacunas de Productos Inactivados , Humanos , COVID-19/prevención & control , COVID-19/inmunología , Femenino , Masculino , Anciano , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/efectos adversos , Vacunas contra la COVID-19/administración & dosificación , SARS-CoV-2/inmunología , Estudios Prospectivos , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/sangre , Vacunas de Productos Inactivados/inmunología , Vacunas de Productos Inactivados/efectos adversos , Vacunas de Productos Inactivados/administración & dosificación , Anticuerpos Neutralizantes/inmunología , Anticuerpos Neutralizantes/sangre , Anciano de 80 o más Años , Adulto , Vacunación , Estudios Longitudinales , Persona de Mediana Edad , Vacunas Sintéticas/inmunología , Vacunas Sintéticas/efectos adversos , Vacunas Sintéticas/administración & dosificación , Inmunogenicidad Vacunal/inmunología , Inmunización Secundaria
15.
Artículo en Inglés | MEDLINE | ID: mdl-38721896

RESUMEN

BACKGROUND: While childhood adversity (CA) is known to be associated with multiple adverse outcomes, its link with dementia is an area with limited exploration and inconsistent agreement. The study aimed to examine the longitudinal associations of CA with incident all-cause dementia and to quantify the potential mediating pathways. METHODS: Data from the UK Biobank. CA, encompassing neglect and abuse, was evaluated retrospectively by an online mental health questionnaire. Physical performance, psychological factors, lifestyles, and biological indicators assessed at baseline were considered potential mediators. Incident all-cause dementia was defined by International Classification of Diseases, Tenth Revision codes obtained through self-reported medical conditions, primary care, hospital admission, and death registrations. Cox proportional hazard models were applied to estimate the longitudinal associations. Mediation analyses were conducted on potential mediators to examine their contribution. RESULTS: This cohort study comprised 150 152 nondemented individuals (mean [SD] age, 55.9 [7.7] years) at baseline (2006-2010). Compared to individuals who did not experience CA, those exposed to any CA exhibited a 30.0% higher risk of dementia (hazard ratio = 1.300, 95% confidence interval [CI]: 1.129-1.496). Each additional CA was associated with a 15.5% (95% CI: 8.8%-22.5%, pfor trend < .001) increased dementia risks. Depression, smoking, and low grip strength explained 8.7%, 2.4%, and 0.9% of the associations, respectively. Biomarkers involving inflammation, erythrocytes, liver, and kidney function mediated the associations by 0.6%-1.4%. CONCLUSIONS: The study revealed the detrimental effects of CA on dementia and identified some potential mediators, namely depression, smoking, low grip strength, and several targeted biomarkers. In addition to calling more attention to CA, the findings underscore the importance of interventions targeting modifiable mediators in preventing dementia.


Asunto(s)
Experiencias Adversas de la Infancia , Bancos de Muestras Biológicas , Demencia , Humanos , Masculino , Femenino , Demencia/epidemiología , Demencia/etiología , Reino Unido/epidemiología , Persona de Mediana Edad , Factores de Riesgo , Experiencias Adversas de la Infancia/estadística & datos numéricos , Anciano , Estudios de Cohortes , Estudios Retrospectivos , Modelos de Riesgos Proporcionales , Estudios Longitudinales , Incidencia , Biobanco del Reino Unido
16.
J Infect ; 89(1): 106181, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38744376

RESUMEN

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging viral hemorrhagic fever with high fatality rates. The blockade of pro-inflammatory cytokines presents a promising therapeutic strategy. METHODS: We conducted a randomized clinical trial at the 154th hospital, Xinyang, Henan Province. Eligible patients with severe SFTS disease were randomly assigned in a 1:2 ratio to receive either a single intravenous infusion of tocilizumab plus usual care; or usual care only. The primary outcome was the clinical status of death/survival at day 14, while secondary outcomes included improvement from baseline in liver and kidney damage and time required for hospital discharge. The efficacy of tocilizumab plus corticosteroid was compared to those receiving corticosteroid alone. The trial is registered with the Chinese Clinical Trial Registry website (ChiCTR2300076317). RESULTS: 63 eligible patients were assigned to the tocilizumab group and 126 to the control group. The addition of tocilizumab to usual care was associated with a reduced death rate (9.5%) compared to those received only usual care (23.0%), with an adjusted hazard ratio (aHR) of 0.37 (95% confidence interval [CI], 0.15 to 0.91, P = 0.029). Combination therapy of tocilizumab and corticosteroids was associated with a significantly reduced fatality (aHR, 0.21; 95% CI, 0.08 to 0.56; P = 0.002) compared to those receiving corticosteroids alone. CONCLUSIONS: A significant benefit of reducing fatality in severe SFTS patients was observed by using tocilizumab. A combined therapy of tocilizumab plus corticosteroids was recommended for the therapy of severe SFTS.


Asunto(s)
Corticoesteroides , Anticuerpos Monoclonales Humanizados , Quimioterapia Combinada , Síndrome de Trombocitopenia Febril Grave , Humanos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Masculino , Femenino , Persona de Mediana Edad , Síndrome de Trombocitopenia Febril Grave/tratamiento farmacológico , Síndrome de Trombocitopenia Febril Grave/mortalidad , Corticoesteroides/uso terapéutico , Corticoesteroides/administración & dosificación , Anciano , Resultado del Tratamiento , Hospitalización/estadística & datos numéricos , China , Adulto
17.
Child Abuse Negl ; 152: 106771, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38581769

RESUMEN

BACKGROUND: Substantial evidence indicates that experiencing physical abuse and neglect during childhood significantly elevates the likelihood of developing depression in adulthood. Nevertheless, there remains a dearth of understanding regarding the mechanisms underpinning this correlation. OBJECTIVE: In this study, we aimed to examine the associations of childhood physical abuse and physical neglect with depression using follow-up data from UK Biobank and quantified the contribution of smoking, insomnia, and BMI in these associations. PARTICIPANTS AND SETTINGS: This study included 144,704 participants (64,168 men and 80,536 women) from UK Biobank, most of whom were white (97 %). METHODS: Physical abuse and physical neglect were measured using two items of Childhood Trauma Screener (CTS). Data on the incidence of depression were obtained from primary care, hospital inpatient records, self-reported medical conditions, and death registries. We used a sequential mediation analysis based on the "g-formula" approach to explore the individual and joint effects of potential mediators. RESULTS: The depression incidence rate was 1.85 per 1000 person-years for men and 2.83 per 1000 person-years for women, respectively. Results of Cox proportional risk regression showed that physical abuse (HRs: 1.39-1.53, P < 0.001) and physical neglect (HRs: 1.43-1.60, P < 0.001) are associated with depression. Smoking, insomnia, and BMI together mediated 3 %-26 % of the associations. CONCLUSIONS: These findings contribute to our understanding of how physical abuse and physical neglect influence depression. Furthermore, a more effective reduction in the burden of depression can be achieved by managing modifiable mediators.


Asunto(s)
Depresión , Humanos , Masculino , Femenino , Persona de Mediana Edad , Reino Unido/epidemiología , Depresión/epidemiología , Incidencia , Adulto , Adultos Sobrevivientes del Maltrato a los Niños/psicología , Adultos Sobrevivientes del Maltrato a los Niños/estadística & datos numéricos , Anciano , Niño , Trastornos del Inicio y del Mantenimiento del Sueño/epidemiología , Trastornos del Inicio y del Mantenimiento del Sueño/psicología , Índice de Masa Corporal , Maltrato a los Niños/psicología , Maltrato a los Niños/estadística & datos numéricos , Abuso Físico/estadística & datos numéricos , Abuso Físico/psicología , Factores de Riesgo , Fumar/epidemiología , Fumar/psicología , Análisis de Mediación
18.
BMC Med ; 22(1): 160, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38616272

RESUMEN

BACKGROUND: Lung health is increasingly recognized as an essential factor in mental health. However, prospective evidence on lung function with incident depression remains to be determined. The study aimed to examine the prospective association between impaired lung function and incident depression and the underlying biological mechanisms. METHODS: This prospective cohort study comprised 280,032 non-depressed individuals with valid lung function measurements from the UK Biobank. Lung function was assessed through the forced vital capacity (FVC) or forced expiratory volume in 1 s (FEV1). Cox proportional hazard models were applied to estimate the associations between lung function and incident depression. Mediation analyses were fitted to investigate the potential mediating role of biomarkers and metabolites in the association. RESULTS: A total of 9514 participants (3.4%) developed depression during a median follow-up of 13.91 years. Individuals in the highest quartile had a lower risk of depression (FVC % predicted: HR = 0.880, 95% CI = 0.830-0.933; FEV1% predicted: HR = 0.854, 95% CI = 0.805-0.905) compared with those in the lowest quartile of the lung function indices. Additionally, the restricted cubic splines suggested lung function indices had reversed J-shaped associations with incident depression (nonlinear P < 0.05 for FVC % predicted and FEV1% predicted). Impaired lung function yielded similar risk estimates (HR = 1.124, 95% CI = 1.074-1.176). Biomarkers involving systemic inflammation, erythrocytes, and liver and renal function may be potential mediators in the lung function-depression association. CONCLUSIONS: This study revealed that the higher risk of developing depression was associated with impaired lung function. Also, the association might be partially mediated by biomarkers including systemic inflammation, erythrocytes, and liver and renal function, though these mediation findings should be interpreted with caution due to potential temporal ambiguity.


Asunto(s)
Depresión , Inflamación , Humanos , Depresión/epidemiología , Estudios Prospectivos , Pulmón , Biomarcadores
19.
Nano Lett ; 24(12): 3801-3810, 2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38477714

RESUMEN

The effectiveness of various cancer therapies for solid tumors is substantially limited by the highly hypoxic tumor microenvironment (TME). Here, a microalgae-integrated living hydrogel (ACG gel) is developed to concurrently enhance hypoxia-constrained tumor starvation therapy and immunotherapy. The ACG gel is formed in situ following intratumoral injection of a biohybrid fluid composed of alginate, Chlorella sorokiniana, and glucose oxidase, facilitated by the crossing-linking between divalent ions within tumors and alginate. The microalgae Chlorella sorokiniana embedded in ACG gel generate abundant oxygen through photosynthesis, enhancing glucose oxidase-catalyzed glucose consumption and shifting the TME from immunosuppressive to immunopermissive status, thus reducing the tumor cell energy supply and boosting antitumor immunity. In murine 4T1 tumor models, the ACG gel significantly suppresses tumor growth and effectively prevents postoperative tumor recurrence. This study, leveraging microalgae as natural oxygenerators, provides a versatile and universal strategy for the development of oxygen-dependent tumor therapies.


Asunto(s)
Chlorella , Microalgas , Neoplasias , Animales , Ratones , Hidrogeles , Glucosa Oxidasa , Fotosíntesis , Hipoxia , Oxígeno , Inmunoterapia , Alginatos , Microambiente Tumoral
20.
Food Res Int ; 177: 113779, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38225109

RESUMEN

Nicotinamide Mononucleotide (NMN) is a derivative of vitamin B3, which plays a significant role in a plethora of metabolic reactions in the human body and is intricately associated with both immunity and metabolism. Nonetheless, in the intestine metabolic pathway of NMN and the relationship between NMN, gut microbiota, and SCFAs remain hitherto obscure. This study examined the digestion of NMN in simulated saliva, gastric, and small intestine environments, as well as exploring the interaction between NMN and human gut microbiota utilizing an in vitro fermentation model. NMN was progressively degraded into nicotinamide ribose (NR), nicotinamide (NAM), and ribose, with niacinate (NA) constituting the ultimate degradation product due to hydrolysis and metabolism by microbiota. NMN was ingested by human intestinal microbiota with a slower fermentation rate. As a result of NMN ingestion by human gut bacteria,the concentrations of propionate and butyrate increased by 88% and 23%, respectively, compared to the blank control group, the proliferation of beneficial gut bacteria (Bifidobacterium, Phascolarctobacterium, Faecalibacteriun, and Alistipes) significantly increased, while the proliferation of some harmful bacteria (Sutterella, Desulfovibrio and Pseudomonas) drastically declined. These findings illustrated the metabolic processes of NMN in the intestine, elaborating the relationship between NMN, SCFAs and gut microbiota. NMN might be a potential prebiotic to improve intestinal health.


Asunto(s)
Microbioma Gastrointestinal , Humanos , Fermentación , Mononucleótido de Nicotinamida/metabolismo , Saliva/metabolismo , Digestión
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